Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control

Eckehard A.E. Stuth, Astrid G. Stucke, Edward J. Zuperku

10.1002/cphy.c100061

Source: Volume 2, Issue 4, October 2012

Published online: October 2012

Full Article on Wiley Online Library



Abstract

This article provides a comprehensive, up to date summary of the effects of volatile, gaseous, and intravenous anesthetics and opioid agonists on ventilatory control. Emphasis is placed on data from human studies. Further mechanistic insights are provided by in vivo and in vitro data from other mammalian species. The focus is on the effects of clinically relevant agonist concentrations and studies using pharmacological, that is, supraclinical agonist concentrations are de‐emphasized or excluded. © 2012 American Physiological Society. Compr Physiol 2:2281‐2367, 2012.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1.

Dose‐dependent effects of volatile anesthesia on cardiorespiratory and clinical parameters in humans. By convention, 1 minimum alveolar concentration (MAC) refers to 1 MACsurgical, which is the anesthetic concentration at which 50% of humans will not show purposeful movement to skin incision; MAC awake: 50% will not recall information; MAC bar: 50% will not have increase in blood pressure and heart rate with skin incision [reproduced with permission of Taylor and Francis Group, Boca Raton, FL from Central Effects of General Anesthesia by Stuth et al. in Pharmacology and Pathophysiology of the Control of Breathing, Volume 202, 2005; permission conveyed through Copyright Clearance Center, Inc. 683].
Figure 2. Figure 2.

Anesthetic effects on the different components of the respiratory center; excitatory receptors are marked red, inhibitory receptors are marked blue. If studies have shown the presence of the receptor but have not investigated the effects of anesthetics the receptor is colored in light colors; if studies have shown that the receptor is affected by anesthetics the receptor is colored with dark colors. Receptors for which conflicting results are published are marked with #. Tandem‐pore acid‐sensitive K+ (TASK) channels serve as modulators of membrane potential and excitability of the cell; they are here marked as “inhibitory” since activation of TASK channels by volatile anesthetics leads to hyperpolarization of the neuron (upward triangle: potentiation of receptor function; downward triangle: inhibition of receptor function; #: conflicting results; *: presynaptic glutamatergic and GABA‐Aergic input reduced by anesthetic; Kat: unidentified kation channel).
Figure 3. Figure 3.

The depression of the hypoxic ventilatory response (HVR) by volatile anesthetics in different, nonprimate mammalian species. Data for this figure were derived from the studies in Table 7 and were analyzed for anesthetic concentration in minimum alveolar concentration (MAC) (top) and Vol% (bottom). Shown are only data for the ratios between control and the lowest FiO2 used in each study. Overall, the depression of the HVR is concentration dependent with less than 50% depression below 1 MAC or below 1 Vol%. A clear difference between species cannot be identified. Differences listed in the literature may be the result of differences in the recording parameters; filled: phrenic nerve recording; hollow: sinus nerve recording; circled in black: MV. Please note that the baseline (control value) for the canine data is 0.5 MAC.
Figure 4. Figure 4.

Depression of the hypoxic ventilatory response (HVR) by isoflurane and enflurane (as indicated) and halothane (all other data points), presented in minimum alveolar concentration (MAC) (top) and Vol% (bottom). Data are derived from studies by Davies et al. 119, Van Dissel et al. 729, and Ponte et al. 551. Please note that these studies used different levels of hypoxia (FiO2); dark blue: FiO2 0.08, light blue: FiO2 0.11 to 0.13, hollow: FiO2 0.16.
Figure 5. Figure 5.

Effects of different anesthetics and different FiO2 on the hypoxic ventilatory response in rabbits. Data are shown for isoflurane and enflurane (as indicated) and halothane (all others) and presented in minimum alveolar concentration (MAC) (top) or Vol% (bottom). Data are derived from studies by Joensen et al. 309 and Ponte et al. 551. The stimulation of the carotid body by lower FiO2, that is, stronger hypoxic stimuli, seems to offset the depression of carotid body function by volatile anesthetics. Overall, halothane up to 1 MAC causes only slight depression of the hypoxic ventilatory response (HVR); dark green: FiO2 0.08, light green: FiO2 0.11 to 0.13, hollow: FiO2 0.16.
Figure 6. Figure 6.

Effects of volatile anesthetics on the CO2 response in cats, rabbits, dogs, and goats. The data are derived, with permission, from studies in Table 8. The study by Biscoe et al. 54 describes only one animal (n = 1). Overall, there is a dose‐dependent depression of the CO2 response by volatile anesthetics; however, this only becomes unequivocally apparent at concentrations greater than 0.5 to 1 minimum alveolar concentration (MAC). Halothane seems to have a greater depressant effect; however, this may be confounded by the fact that the other anesthetics were only tested at lower concentrations. No clear difference seems to exist between species. Red: halothane, purple: isoflurane, orange: enflurane.
Figure 7. Figure 7.

Effects of volatile anesthetics on the hypoxic ventilatory response (HVR) and the carotid body‐mediated CO2 response in rabbits and cats. All data are taken from the publication by Ponte et al. 551, which used a uniform preparation, so that blood pressure and thus carotid body discharge were likely changed to a similar degree in all substudies. The results suggest that in both species all volatile anesthetics depress the peripheral CO2 response less than the HVR. Circles: rabbit, triangle: cat; hollow symbols: HVR, filled symbols: CO2 response, red: halothane, purple: isoflurane, orange: enflurane.
Figure 8. Figure 8.

Effects of the volatile anesthetics halothane (H), isoflurane (I), enflurane (E), and sevoflurane (S) on the neuronal discharge activity of respiratory neurons in animals without the use of background anesthesia. (A) shows data from inspiratory (solid line) and expiratory (dashed line) premotor neurons in the caudal ventral respiratory group in neuraxis‐intact (a‐c) and decerebrate dogs (d‐j). (a) refers to reference 685, (b) to reference 684, (c) to reference 682, (d) to reference 681, (e) to reference 668, (f) to reference 669, (g) to reference 674, (h) to reference 666, (i) to reference 667, and (j) to reference 664. The data are normalized to the neuronal discharge frequency at 0 minimum alveolar concentration (MAC) (decerebrate animals) or 1 MAC anesthesia (intact animals). (B) shows data from inspiratory neurons in the region of the nucleus ambiguus of the ventral respiratory group in cats. In two studies, the authors compared the effects of halothane and sevoflurane (k = 134) and halothane and enflurane (l = 317) with crossover administration of the two agents while recording from the same neuron. The neuronal discharge activity was normalized to the frequency at 1 MAC halothane for each study. (C) compares the effects of halothane (m = 686) and enflurane (n = 685) on inspiratory neurons in the dorsal respiratory group in decerebrate cats. The data are normalized to the neuronal discharge activity at 0 MAC for both studies. Figure 8A‐C is reproduced with permission of Taylor and Francis Group, Boca Raton, FL from Central Effects of General Anesthesia by Stuth et.al in Pharmacology and Pathophysiology of the Control of Breathing, Volume 202, 2005; permission conveyed through Copyright Clearance Center, Inc. 683.
Figure 9. Figure 9.

(Top) Depression of the hypoxic ventilatory response (HVR) by volatile anesthetics in human subjects; data originate from different studies and were compiled by 526. Data are presented as the ratio between the HVR under anesthesia vs. preanesthesia control. The data indicate that despite considerable variability amongst anesthetics and between studies the HVR is already significantly depressed by subanesthetic concentrations of some volatile anesthetics. (Bottom) The hypercapnic ventilatory response in human subjects; data originate from different studies and were compiled by 527. Data are presented as the ratio between the hypercapnic responses under anesthesia versus preanesthesia control. Compared to the HVR the peripheral hypercapnic response is much less depressed at subanesthetic levels of volatile anesthetics. Red: halothane, purple: isoflurane, orange: enflurane, green: sevoflurane, hollow diamond: desflurane, hollow circle: nitrous oxide.
Figure 10. Figure 10.

Physiologically relevant synaptic inputs during the active phase of canine respiratory bulbospinal neurons (BSNs). Inspiratory BSNs receive phasic and tonic excitatory drive (Fe) through AMPA and NMDA receptors while expiratory BSNs receive only tonic excitatory drive via NMDA receptors. The total excitatory drive is attenuated via gain modulation by tonic inhibition (α), which is mediated by GABA‐A receptors and can be blocked with bicuculline. Neuronal control discharge frequency (Fcon, green output) is thus the product of overall excitation (red inputs) and inhibition (blue inputs). Fn: neuronal discharge frequency; Fcon: gain modulated baseline Fn under control conditions; Fe: Fcon observed during complete block of GABA‐A receptor‐mediated gain modulation (α = 0) that reflects the unmodulated, that is, not attenuated transmission of glutamatergic excitatory drive to BSNs [modified, with permission, from figure 1 in Respiratory Physiology and Neurobiology, Volume 164 (2008), 151‐159, Stuth et al. Anesthetic effects on synaptic neurotransmission and gain control in respiratory control, with permission from Elsevier B.V. 677].
Figure 11. Figure 11.

Analysis of the response of an inspiratory bulbospinal respiratory neuron to the GABA‐A antagonist bicuculline (BIC) at 0 and 1 minimum alveolar concentration (MAC) sevoflurane to estimate anesthetic effects on overall synaptic neurotransmission: Rate‐meter recordings of neuronal discharge frequency Fn (in hertz) are shown during picoejection at increasing dose rates of BIC until no further increase in Fn is observed, that is, until all BIC‐sensitive GABA‐A receptors are blocked. At the point of complete GABAergic block, Fn reflects the overall excitatory input to the neuron, Fe. The factor by which neuronal frequency under control conditions (Fcon) is attenuated from Fe is the overall inhibition (α). This method thus allows estimation of the anesthetic effect on overall excitation and overall inhibition (α). Subscripts indicate 0 = 0 MAC, 1 = 1 MAC. Bars on right are mean peak discharge frequencies. In this neuron overall inhibition was enhanced by 31% (Δα = 100(α1‐α0)/α0,) while overall excitation was decreased by 9% (ΔFe = 100(Fe1‐Fe0)/Fe0) [reprinted, with permission, from Respiratory Physiology and Neurobiology, Volume 164 (2008), 151‐159, Stuth et al. Anesthetic effects on synaptic neurotransmission and gain control in respiratory control, with permission from Elsevier B.V. 677].
Figure 12. Figure 12.

Summary data of the effects of 1 minimum alveolar concentration (MAC) halothane and 1 MAC sevoflurane on inspiratory (IBSN) and expiratory (EBSN) bulbospinal neurons in dogs: the anesthetic effects on control frequency (Fcon) are divided into effects on overall glutamatergic excitation (Fe) (in red) and overall GABAergic inhibition (α) (in blue) and these effects are further separated into their presynaptic and postsynaptic components. Significant anesthesia‐induced changes are shown as increases or decreases compared to control. Ø: no significant change. For presynaptic changes, which cannot be directly measured but only estimated, assuming cascaded effects, the trend is indicated. + = excitatory glutamatergic inputs (red); − = inhibitory GABAergic inputs (blue). Anesthetic effects on neurotransmission in this decerebrate canine paradigm are only assessed for the active phase of each neuron type when extracellular discharge activity is present and can be recorded [reprinted, with permission, from Respiratory Physiology and Neurobiology, Volume 164 (2008), 151‐159, Stuth et al. Anesthetic effects on synaptic neurotransmission and gain control in respiratory control, with permission from Elsevier B.V. 677].
Figure 13. Figure 13.

Summary of the clinical effects of opioids on brainstem respiratory neurons. The scheme is based on data from references 363,671, and 479. The effects on membrane potential and discharge activity of the neurons as well as central inspiratory activity are linked hypothetically to observed clinical effects in animals and humans. Red frame: presence of functional opioid receptors was demonstrated on these neurons/structures; arrow: projecting to downstream neuron group; BSNs: bulbospinal neurons; MNs: motoneurons.
Figure 14. Figure 14.

Effect of halothane and 5‐HT on a hypoglossal motoneuron in an in vitro, neonatal rodent brainstem slice. A hypoglossal motoneuron was induced to discharge action potentials by direct, depolarizing current injection under current clamp conditions. Exposure to a 1.3 minimum alveolar concentration (MAC) dose (0.35 mM, equivalent to a clinical ED95) of halothane in the bath solution caused neuronal membrane hyperpolarization, which resulted in suppression of action potential discharges. Despite the continued presence of halothane the anesthetic‐induced hyperpolarization could be reversed by serotonin with resumption of neuronal firing, suggesting that halothane acted in opposite direction to a serotonin‐responsive mechanisms such as tandem‐pore acid‐sensitive K+ (TASK) channels. [reproduced with permission of Journal of Physiology from Volume 541: 717‐729, 2002 : Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anesthetic and neurotransmitters in rat brainstem motoneurons by Sirois et al.; permission conveyed through Copyright Clearance Center, Inc. 640].
Figure 15. Figure 15.

Increase in motoneuronal excitability by serotonin (5‐HT) in a neonatal rodent slice preparation. Serotonin‐inhibited acid sensitive K+ channels [tandem‐pore acid‐sensitive K+ (TASK)] as shown by the inward shift in the neuronal membrane holding current. Halothane caused opposite effects in the membrane current and the serotonin‐induced inward shift in current was enhanced in the presence of halothane. This suggests that serotonin prevails over halothane concerning their reciprocal effects on TASK channels. A confounding hyperpolarization‐activated cationic current (Ih) that is also present in these neurons and also modulated by halothane was removed by pharmacological block in this protocol. [reproduced with permission of Journal of Physiology from Volume 541: 717‐729, 2002 : Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anesthetic and neurotransmitters in rat brainstem motoneurons by Sirois et al.; permission conveyed through Copyright Clearance Center, Inc. 640].
Figure 16. Figure 16.

Scheme of the expected and observed effects of isoflurane and serotonin on the discharge frequency pattern (Fn) of canine inspiratory hypoglossal motoneurons in vivo. The observed effect on the discharge pattern for each condition was averaged from the response of 19 neurons in an in vivo canine preparation. Neuronal discharge under control conditions (control, thick solid line) was decreased by 0.3 minimum alveolar concentration (MAC) isoflurane (iso, thick interrupted line). Ejection of near maximal doses of serotonin onto the neurons increased neuronal discharge frequency (5‐HT, thick solid line). The study investigated whether neuronal K+‐leak (TASK) channels were responsible for the anesthetic depression of Fn. In vitro studies have shown that isoflurane opens TASK channels leading to membrane hyperpolarization while serotonin completely antagonizes TASK channel activation (adapted, with permission, from reference 640). It was thus expected (upper panel) that the depression of Fn by isoflurane (downward arrow) would be completely reversed and Fn would increase (upward arrow) to Fn during maximal serotonin ejection (5‐HT and 5‐HT+iso). Indeed it was observed (lower panel) that isoflurane depressed Fn (iso); however, ejection of serotonin raised Fn far less (5‐HT+iso) than it had without isoflurane (5‐HT). This would indicate that TASK channel blockade with serotonin could not reverse the anesthetic depression of Fn suggesting that TASK channels do not play a significant role in this depression. Data adapted from reference 71).
Figure 17. Figure 17.

Effects of volatile anesthesia on clinical respiratory parameters in humans. The data are compiled, with permission, from studies in references 80,137,190,269, and 391) and the figure is modified, with permission, from reference 178 [reproduced with permission of Taylor and Francis Group, Boca Raton, FL from Central Effects of General Anesthesia by Stuth et al. in Pharmacology and Pathophysiology of the Control of Breathing, Volume 202, 2005; permission conveyed through Copyright Clearance Center, Inc. 683.


Figure 1.

Dose‐dependent effects of volatile anesthesia on cardiorespiratory and clinical parameters in humans. By convention, 1 minimum alveolar concentration (MAC) refers to 1 MACsurgical, which is the anesthetic concentration at which 50% of humans will not show purposeful movement to skin incision; MAC awake: 50% will not recall information; MAC bar: 50% will not have increase in blood pressure and heart rate with skin incision [reproduced with permission of Taylor and Francis Group, Boca Raton, FL from Central Effects of General Anesthesia by Stuth et al. in Pharmacology and Pathophysiology of the Control of Breathing, Volume 202, 2005; permission conveyed through Copyright Clearance Center, Inc. 683].



Figure 2.

Anesthetic effects on the different components of the respiratory center; excitatory receptors are marked red, inhibitory receptors are marked blue. If studies have shown the presence of the receptor but have not investigated the effects of anesthetics the receptor is colored in light colors; if studies have shown that the receptor is affected by anesthetics the receptor is colored with dark colors. Receptors for which conflicting results are published are marked with #. Tandem‐pore acid‐sensitive K+ (TASK) channels serve as modulators of membrane potential and excitability of the cell; they are here marked as “inhibitory” since activation of TASK channels by volatile anesthetics leads to hyperpolarization of the neuron (upward triangle: potentiation of receptor function; downward triangle: inhibition of receptor function; #: conflicting results; *: presynaptic glutamatergic and GABA‐Aergic input reduced by anesthetic; Kat: unidentified kation channel).



Figure 3.

The depression of the hypoxic ventilatory response (HVR) by volatile anesthetics in different, nonprimate mammalian species. Data for this figure were derived from the studies in Table 7 and were analyzed for anesthetic concentration in minimum alveolar concentration (MAC) (top) and Vol% (bottom). Shown are only data for the ratios between control and the lowest FiO2 used in each study. Overall, the depression of the HVR is concentration dependent with less than 50% depression below 1 MAC or below 1 Vol%. A clear difference between species cannot be identified. Differences listed in the literature may be the result of differences in the recording parameters; filled: phrenic nerve recording; hollow: sinus nerve recording; circled in black: MV. Please note that the baseline (control value) for the canine data is 0.5 MAC.



Figure 4.

Depression of the hypoxic ventilatory response (HVR) by isoflurane and enflurane (as indicated) and halothane (all other data points), presented in minimum alveolar concentration (MAC) (top) and Vol% (bottom). Data are derived from studies by Davies et al. 119, Van Dissel et al. 729, and Ponte et al. 551. Please note that these studies used different levels of hypoxia (FiO2); dark blue: FiO2 0.08, light blue: FiO2 0.11 to 0.13, hollow: FiO2 0.16.



Figure 5.

Effects of different anesthetics and different FiO2 on the hypoxic ventilatory response in rabbits. Data are shown for isoflurane and enflurane (as indicated) and halothane (all others) and presented in minimum alveolar concentration (MAC) (top) or Vol% (bottom). Data are derived from studies by Joensen et al. 309 and Ponte et al. 551. The stimulation of the carotid body by lower FiO2, that is, stronger hypoxic stimuli, seems to offset the depression of carotid body function by volatile anesthetics. Overall, halothane up to 1 MAC causes only slight depression of the hypoxic ventilatory response (HVR); dark green: FiO2 0.08, light green: FiO2 0.11 to 0.13, hollow: FiO2 0.16.



Figure 6.

Effects of volatile anesthetics on the CO2 response in cats, rabbits, dogs, and goats. The data are derived, with permission, from studies in Table 8. The study by Biscoe et al. 54 describes only one animal (n = 1). Overall, there is a dose‐dependent depression of the CO2 response by volatile anesthetics; however, this only becomes unequivocally apparent at concentrations greater than 0.5 to 1 minimum alveolar concentration (MAC). Halothane seems to have a greater depressant effect; however, this may be confounded by the fact that the other anesthetics were only tested at lower concentrations. No clear difference seems to exist between species. Red: halothane, purple: isoflurane, orange: enflurane.



Figure 7.

Effects of volatile anesthetics on the hypoxic ventilatory response (HVR) and the carotid body‐mediated CO2 response in rabbits and cats. All data are taken from the publication by Ponte et al. 551, which used a uniform preparation, so that blood pressure and thus carotid body discharge were likely changed to a similar degree in all substudies. The results suggest that in both species all volatile anesthetics depress the peripheral CO2 response less than the HVR. Circles: rabbit, triangle: cat; hollow symbols: HVR, filled symbols: CO2 response, red: halothane, purple: isoflurane, orange: enflurane.



Figure 8.

Effects of the volatile anesthetics halothane (H), isoflurane (I), enflurane (E), and sevoflurane (S) on the neuronal discharge activity of respiratory neurons in animals without the use of background anesthesia. (A) shows data from inspiratory (solid line) and expiratory (dashed line) premotor neurons in the caudal ventral respiratory group in neuraxis‐intact (a‐c) and decerebrate dogs (d‐j). (a) refers to reference 685, (b) to reference 684, (c) to reference 682, (d) to reference 681, (e) to reference 668, (f) to reference 669, (g) to reference 674, (h) to reference 666, (i) to reference 667, and (j) to reference 664. The data are normalized to the neuronal discharge frequency at 0 minimum alveolar concentration (MAC) (decerebrate animals) or 1 MAC anesthesia (intact animals). (B) shows data from inspiratory neurons in the region of the nucleus ambiguus of the ventral respiratory group in cats. In two studies, the authors compared the effects of halothane and sevoflurane (k = 134) and halothane and enflurane (l = 317) with crossover administration of the two agents while recording from the same neuron. The neuronal discharge activity was normalized to the frequency at 1 MAC halothane for each study. (C) compares the effects of halothane (m = 686) and enflurane (n = 685) on inspiratory neurons in the dorsal respiratory group in decerebrate cats. The data are normalized to the neuronal discharge activity at 0 MAC for both studies. Figure 8A‐C is reproduced with permission of Taylor and Francis Group, Boca Raton, FL from Central Effects of General Anesthesia by Stuth et.al in Pharmacology and Pathophysiology of the Control of Breathing, Volume 202, 2005; permission conveyed through Copyright Clearance Center, Inc. 683.



Figure 9.

(Top) Depression of the hypoxic ventilatory response (HVR) by volatile anesthetics in human subjects; data originate from different studies and were compiled by 526. Data are presented as the ratio between the HVR under anesthesia vs. preanesthesia control. The data indicate that despite considerable variability amongst anesthetics and between studies the HVR is already significantly depressed by subanesthetic concentrations of some volatile anesthetics. (Bottom) The hypercapnic ventilatory response in human subjects; data originate from different studies and were compiled by 527. Data are presented as the ratio between the hypercapnic responses under anesthesia versus preanesthesia control. Compared to the HVR the peripheral hypercapnic response is much less depressed at subanesthetic levels of volatile anesthetics. Red: halothane, purple: isoflurane, orange: enflurane, green: sevoflurane, hollow diamond: desflurane, hollow circle: nitrous oxide.



Figure 10.

Physiologically relevant synaptic inputs during the active phase of canine respiratory bulbospinal neurons (BSNs). Inspiratory BSNs receive phasic and tonic excitatory drive (Fe) through AMPA and NMDA receptors while expiratory BSNs receive only tonic excitatory drive via NMDA receptors. The total excitatory drive is attenuated via gain modulation by tonic inhibition (α), which is mediated by GABA‐A receptors and can be blocked with bicuculline. Neuronal control discharge frequency (Fcon, green output) is thus the product of overall excitation (red inputs) and inhibition (blue inputs). Fn: neuronal discharge frequency; Fcon: gain modulated baseline Fn under control conditions; Fe: Fcon observed during complete block of GABA‐A receptor‐mediated gain modulation (α = 0) that reflects the unmodulated, that is, not attenuated transmission of glutamatergic excitatory drive to BSNs [modified, with permission, from figure 1 in Respiratory Physiology and Neurobiology, Volume 164 (2008), 151‐159, Stuth et al. Anesthetic effects on synaptic neurotransmission and gain control in respiratory control, with permission from Elsevier B.V. 677].



Figure 11.

Analysis of the response of an inspiratory bulbospinal respiratory neuron to the GABA‐A antagonist bicuculline (BIC) at 0 and 1 minimum alveolar concentration (MAC) sevoflurane to estimate anesthetic effects on overall synaptic neurotransmission: Rate‐meter recordings of neuronal discharge frequency Fn (in hertz) are shown during picoejection at increasing dose rates of BIC until no further increase in Fn is observed, that is, until all BIC‐sensitive GABA‐A receptors are blocked. At the point of complete GABAergic block, Fn reflects the overall excitatory input to the neuron, Fe. The factor by which neuronal frequency under control conditions (Fcon) is attenuated from Fe is the overall inhibition (α). This method thus allows estimation of the anesthetic effect on overall excitation and overall inhibition (α). Subscripts indicate 0 = 0 MAC, 1 = 1 MAC. Bars on right are mean peak discharge frequencies. In this neuron overall inhibition was enhanced by 31% (Δα = 100(α1‐α0)/α0,) while overall excitation was decreased by 9% (ΔFe = 100(Fe1‐Fe0)/Fe0) [reprinted, with permission, from Respiratory Physiology and Neurobiology, Volume 164 (2008), 151‐159, Stuth et al. Anesthetic effects on synaptic neurotransmission and gain control in respiratory control, with permission from Elsevier B.V. 677].



Figure 12.

Summary data of the effects of 1 minimum alveolar concentration (MAC) halothane and 1 MAC sevoflurane on inspiratory (IBSN) and expiratory (EBSN) bulbospinal neurons in dogs: the anesthetic effects on control frequency (Fcon) are divided into effects on overall glutamatergic excitation (Fe) (in red) and overall GABAergic inhibition (α) (in blue) and these effects are further separated into their presynaptic and postsynaptic components. Significant anesthesia‐induced changes are shown as increases or decreases compared to control. Ø: no significant change. For presynaptic changes, which cannot be directly measured but only estimated, assuming cascaded effects, the trend is indicated. + = excitatory glutamatergic inputs (red); − = inhibitory GABAergic inputs (blue). Anesthetic effects on neurotransmission in this decerebrate canine paradigm are only assessed for the active phase of each neuron type when extracellular discharge activity is present and can be recorded [reprinted, with permission, from Respiratory Physiology and Neurobiology, Volume 164 (2008), 151‐159, Stuth et al. Anesthetic effects on synaptic neurotransmission and gain control in respiratory control, with permission from Elsevier B.V. 677].



Figure 13.

Summary of the clinical effects of opioids on brainstem respiratory neurons. The scheme is based on data from references 363,671, and 479. The effects on membrane potential and discharge activity of the neurons as well as central inspiratory activity are linked hypothetically to observed clinical effects in animals and humans. Red frame: presence of functional opioid receptors was demonstrated on these neurons/structures; arrow: projecting to downstream neuron group; BSNs: bulbospinal neurons; MNs: motoneurons.



Figure 14.

Effect of halothane and 5‐HT on a hypoglossal motoneuron in an in vitro, neonatal rodent brainstem slice. A hypoglossal motoneuron was induced to discharge action potentials by direct, depolarizing current injection under current clamp conditions. Exposure to a 1.3 minimum alveolar concentration (MAC) dose (0.35 mM, equivalent to a clinical ED95) of halothane in the bath solution caused neuronal membrane hyperpolarization, which resulted in suppression of action potential discharges. Despite the continued presence of halothane the anesthetic‐induced hyperpolarization could be reversed by serotonin with resumption of neuronal firing, suggesting that halothane acted in opposite direction to a serotonin‐responsive mechanisms such as tandem‐pore acid‐sensitive K+ (TASK) channels. [reproduced with permission of Journal of Physiology from Volume 541: 717‐729, 2002 : Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anesthetic and neurotransmitters in rat brainstem motoneurons by Sirois et al.; permission conveyed through Copyright Clearance Center, Inc. 640].



Figure 15.

Increase in motoneuronal excitability by serotonin (5‐HT) in a neonatal rodent slice preparation. Serotonin‐inhibited acid sensitive K+ channels [tandem‐pore acid‐sensitive K+ (TASK)] as shown by the inward shift in the neuronal membrane holding current. Halothane caused opposite effects in the membrane current and the serotonin‐induced inward shift in current was enhanced in the presence of halothane. This suggests that serotonin prevails over halothane concerning their reciprocal effects on TASK channels. A confounding hyperpolarization‐activated cationic current (Ih) that is also present in these neurons and also modulated by halothane was removed by pharmacological block in this protocol. [reproduced with permission of Journal of Physiology from Volume 541: 717‐729, 2002 : Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anesthetic and neurotransmitters in rat brainstem motoneurons by Sirois et al.; permission conveyed through Copyright Clearance Center, Inc. 640].



Figure 16.

Scheme of the expected and observed effects of isoflurane and serotonin on the discharge frequency pattern (Fn) of canine inspiratory hypoglossal motoneurons in vivo. The observed effect on the discharge pattern for each condition was averaged from the response of 19 neurons in an in vivo canine preparation. Neuronal discharge under control conditions (control, thick solid line) was decreased by 0.3 minimum alveolar concentration (MAC) isoflurane (iso, thick interrupted line). Ejection of near maximal doses of serotonin onto the neurons increased neuronal discharge frequency (5‐HT, thick solid line). The study investigated whether neuronal K+‐leak (TASK) channels were responsible for the anesthetic depression of Fn. In vitro studies have shown that isoflurane opens TASK channels leading to membrane hyperpolarization while serotonin completely antagonizes TASK channel activation (adapted, with permission, from reference 640). It was thus expected (upper panel) that the depression of Fn by isoflurane (downward arrow) would be completely reversed and Fn would increase (upward arrow) to Fn during maximal serotonin ejection (5‐HT and 5‐HT+iso). Indeed it was observed (lower panel) that isoflurane depressed Fn (iso); however, ejection of serotonin raised Fn far less (5‐HT+iso) than it had without isoflurane (5‐HT). This would indicate that TASK channel blockade with serotonin could not reverse the anesthetic depression of Fn suggesting that TASK channels do not play a significant role in this depression. Data adapted from reference 71).



Figure 17.

Effects of volatile anesthesia on clinical respiratory parameters in humans. The data are compiled, with permission, from studies in references 80,137,190,269, and 391) and the figure is modified, with permission, from reference 178 [reproduced with permission of Taylor and Francis Group, Boca Raton, FL from Central Effects of General Anesthesia by Stuth et al. in Pharmacology and Pathophysiology of the Control of Breathing, Volume 202, 2005; permission conveyed through Copyright Clearance Center, Inc. 683.

References
 1. ULTIVA (remifentanil hydrochloride) for injection, [package insert]. Lake Forest, IL: Bioniche Pharma USA LLC; 2009. http://www.ultiva.com/resources.aspx
 2. Abrams JT, Horrow JC, Bennett JA, Van Riper DF, Storella RJ. Upper airway closure: A primary source of difficult ventilation with sufentanil induction of anesthesia. Anesth Analg 83: 629‐632, 1996.
 3. Adachi YU, Watanabe K, Higuchi H, Satoh T. The determinants of propofol induction of anesthesia dose. Anesth Analg 92: 656‐661, 2001.
 4. Akada S, Fagerlund MJ, Lindahl SG, Sakamoto A, Prabhakar NR, Eriksson LI. Pronounced depression by propofol on carotid body response to CO2 and K+‐induced carotid body activation. Respir Physiol Neurobiol 160: 284‐288, 2008.
 5. Alexander CM, Gross JB. Sedative doses of midazolam depress hypoxic ventilatory responses in humans. Anesth Analg 67: 377‐382, 1988.
 6. Alheid GF, Milsom WK, McCrimmon DR. Pontine influences on breathing: An overview. Respir Physiol Neurobiol 143: 105‐114, 2004.
 7. Aliverti A, Kostic P, Lo Mauro A, Andersson‐Olerud M, Quaranta M, Pedotti A, Hedenstierna G, Frykholm P. Effects of propofol anaesthesia on thoraco‐abdominal volume variations during spontaneous breathing and mechanical ventilation. Acta Anaesthesiol Scand 55: 588‐596, 2011.
 8. Alkire MT, McReynolds JR, Hahn EL, Trivedi AN. Thalamic microinjection of nicotine reverses sevoflurane‐induced loss of righting reflex in the rat. Anesthesiology 107: 264‐272, 2007.
 9. Allsop P, Taylor MB, Grounds RM, Morgan M. Ventilatory effects of a propofol infusion using a method to rapidly achieve steady‐state equilibrium. Eur J Anaesthesiol 5: 293‐303, 1988.
 10. Amin HM, Sopchak AM, Esposito BF, Henson LG, Batenhorst RL, Fox AW, Camporesi EM. Naloxone‐induced and spontaneous reversal of depressed ventilatory responses to hypoxia during and after continuous infusion of remifentanil or alfentanil. J Pharmacol Exp Ther 274: 34‐39, 1995.
 11. Andoh T, Furuya R, Oka K, Hattori S, Watanabe I, Kamiya Y, Okumura F. Differential effects of thiopental on neuronal nicotinic acetylcholine receptors and P2X purinergic receptors in PC12 cells. Anesthesiology 87: 1199‐1209, 1997.
 12. Anis NA, Berry SC, Burton NR, Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐D‐aspartate. Br J Pharmacol 79: 565‐575, 1983.
 13. Antkowiak B. Different actions of general anesthetics on the firing patterns of neocortical neurons mediated by the GABAA receptor. Anesthesiology 91: 500‐511, 1999.
 14. Antkowiak B. How do general anaesthetics work? Naturwissenschaften 88: 201‐213, 2001.
 15. Antognini JF, Carstens E, Tabo E, Buzin V. Effect of differential delivery of isoflurane to head and torso on lumbar dorsal horn activity. Anesthesiology 88: 1055‐1061, 1998.
 16. Antognini JF, Schwartz K. Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology 79: 1244‐1249, 1993.
 17. Arunasalam K, Davenport HT, Painter S, Jones JG. Ventilatory response to morphine in young and old subjects. Anaesthesia 38: 529‐533, 1983.
 18. Babenco HD, Conard PF, Gross JB. The pharmacodynamic effect of a remifentanil bolus on ventilatory control. Anesthesiology 92: 393‐398, 2000.
 19. Badrinath S, Avramov MN, Shadrick M, Witt TR, Ivankovich AD. The use of a ketamine‐propofol combination during monitored anesthesia care. Anesth Analg 90: 858‐862, 2000.
 20. Bai D, Pennefather PS, MacDonald JF, Orser BA. The general anesthetic propofol slows deactivation and desensitization of GABA(A) receptors. J Neurosci 19: 10635‐10646, 1999.
 21. Bai D, Zhu G, Pennefather P, Jackson MF, MacDonald JF, Orser BA. Distinct functional and pharmacological properties of tonic and quantal inhibitory postsynaptic currents mediated by gamma‐aminobutyric acid(A) receptors in hippocampal neurons. Mol Pharmacol 59: 814‐824, 2001.
 22. Bailey PL, Lu JK, Pace NL, Orr JA, White JL, Hamber EA, Slawson MH, Crouch DJ, Rollins DE. Effects of intrathecal morphine on the ventilatory response to hypoxia. N Engl J Med 343: 1228‐1234, 2000.
 23. Bailey PL, Pace NL, Ashburn MA, Moll JW, East KA, Stanley TH. Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. Anesthesiology 73: 826‐830, 1990.
 24. Bailey PL, Rhondeau S, Schafer PG, Lu JK, Timmins BS, Foster W, Pace NL, Stanley TH. Dose‐response pharmacology of intrathecal morphine in human volunteers. Anesthesiology 79: 49‐59; discussion 25A, 1993.
 25. Bailey PL, Streisand JB, East KA, East TD, Isern S, Hansen TW, Posthuma EF, Rozendaal FW, Pace NL, Stanley TH. Differences in magnitude and duration of opioid‐induced respiratory depression and analgesia with fentanyl and sufentanil. Anesth Analg 70: 8‐15, 1990.
 26. Bailey PL, Thakur, R. Chapter 13 pain management and regional anesthesia. In: Denham S, Ward AD, Teppema LJ, editors. Pharmacology and Pathophysiology of the Control of Breathing. Boca Raton: Taylor and Francis Group, 2005, pp. 425‐512.
 27. Ballanyi K, Lalley PM, Hoch B, Richter DW. cAMP‐dependent reversal of opioid‐ and prostaglandin‐mediated depression of the isolated respiratory network in newborn rats. J Physiol 504: 127‐134, 1997.
 28. Ballanyi K, Onimaru H, Homma I. Respiratory network function in the isolated brainstem‐spinal cord of newborn rats. Prog Neurobiol 59: 583‐634, 1999.
 29. Bally B, Payen JF, Serre‐Debeauvais F, Tranchand B, Gavend M, Stieglitz P. Pharmacokinetics of methohexital given by constant rate intravenous infusion. Ann Fr Anesth Reanim 11: 136‐140, 1992.
 30. Banks MI, Pearce RA. Dual actions of volatile anesthetics on GABAA IPSCs: Dissociation of blocking and prolonging effects. Anesthesiology 90: 120‐134, 1999.
 31. Banks MI, Pearce RA. Kinetic differences between synaptic and extrasynaptic GABAA receptors in CA1 pyramidal cells. J Neurophysiol 20: 937‐948, 2000.
 32. Bao YP, Williamson G, Tew D, Plumb GW, Lambert N, Jones JG, Menon DK. Antioxidant effects of propofol in human hepatic microsomes: Concentration effects and clinical relevance. Br J Anaesth 81: 584‐589, 1998.
 33. Barnes BJ, Tuong CM, Mellen NM. Functional imaging reveals respiratory network activity during hypoxic and opioid challenge in the neonate rat tilted sagittal slab preparation. J Neurophysiol 97: 2283‐2292, 2007.
 34. Barr J, Zomorodi K, Bertaccini EJ, Shafer SL, Geller E. A double‐blind, randomized comparison of i.v. lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model. Anesthesiology 95: 286‐298, 2001.
 35. Bartlett D Jr., St. John WM. Influence of morphine on respiratory activities of phrenic and hypoglossal nerves in cats. RespirPhysiol 64: 289‐294, 1986.
 36. Baum VC, Yemen TA, Baum LD. Immediate 8% sevoflurane induction in children: A comparison with incremental sevoflurane and incremental halothane. Anesth Analg 85: 313‐316, 1997.
 37. Bayliss DA, Talley EM, Sirois JE, Lei Q. TASK‐1 is a highly modulated pH‐sensitive “leak” K+ channel expressed in brainstem respiratory neurons. Respir Physiol 129: 159‐174, 2001.
 38. Bayliss DA, Viana F, Talley EM, Berger AJ. Neuromodulation of hypoglossal motoneurons: Cellular and developmental mechanisms. Respir Physiol 110: 139‐150, 1997.
 39. Becker LD, Paulson BA, Miller RD, Severinghaus JW, Eger EI 2nd. Biphasic respiratory depression after fentanyldroperidol or fentanyl alone used to supplement nitrous oxide anesthesia. Anesthesiology 44: 291‐296, 1976.
 40. Bell GD, Spickett GP, Reeve PA, Morden A, Logan RF. Intravenous midazolam for upper gastrointestinal endoscopy: A study of 800 consecutive cases relating dose to age and sex of patient. Br J Clin Pharmacol 23: 241‐243, 1987.
 41. Belleville JP, Ward DS, Bloor BC, Maze M. Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology 77: 1125‐1133, 1992.
 42. Bellville JW, Whipp BJ, Kaufman RD, Swanson GD, Aqleh KA, Wiberg DM. Central and peripheral chemoreflex loop gain in normal and carotid body‐resected subjects. JApplPhysiol 46 (4): 843‐853, 1979.
 43. Bennett JA, Abrams JT, Van Riper DF, Horrow JC. Difficult or impossible ventilation after sufentanil‐induced anesthesia is caused primarily by vocal cord closure. Anesthesiology 87: 1070‐1074, 1997.
 44. Benot AR, Lopez‐Barneo J. Feedback inhibition of Ca2+ currents by dopamine in glomus cells of the carotid body. Eur J Neurosci 2: 809‐812, 1990.
 45. Berger AJ. Determinants of respiratory motoneuron output. Respir Physiol 122: 259‐269, 2000.
 46. Berkenbosch A, Bovill JG, Dahan A, DeGoede J, Olievier IC. The ventilatory CO2 sensitivities from Read's rebreathing method and the steady‐state method are not equal in man. J Physiol 411: 367‐377, 1989.
 47. Berkenbosch A, DeGoede J, Ward DS, Olievier CN, Vanhartevelt J. Dynamic response of peripheral chemoreflex loop to changes in end‐tidal CO2. JApplPhysiol 64: 1779‐1785, 1988.
 48. Berkenbosch A, Heeringa J, Olievier CN, Kruyt EW. Artificial pefusion of the ponto‐medullary region of cats. A method for separation of central and peripheral effects of chemical stimulation of ventilation. Respir Physiol 37: 347‐364, 1979.
 49. Berkenbosch A, Olievier CN, Wolsink JG, DeGoede J, Rupreht J. Effects of morphine and physostigmine on the ventilatory response to carbon dioxide. Anesthesiology 80: 1303‐1310, 1994.
 50. Berkenbosch A, Teppema LJ, Olievier CN, Dahan A. Influences of morphine on the ventilatory response to isocapnic hypoxia. Anesthesiology 86: 1342‐1349, 1997.
 51. Bianchi AL, Denavit‐Saubie M, Champagnat J. Central control of breathing in mammals: Neuronal circuitry, membrane properties, and neurotransmitters. PhysiolRev 75 (1): 1‐45, 1995.
 52. Bickler PE, Dueck R, Prutow RJ. Effects of barbiturate anesthesia on functional residual capacity and ribcage/diaphragm contributions to ventilation. Anesthesiology 66: 147‐152, 1987.
 53. Biscoe TJ, Millar RA. Effects of inhalation anaesthetics on carotid body chemoreceptor activity. Br J Anaesth 40: 2‐12, 1968.
 54. Black ML, Hill JL, Zacny JP. Behavioral and physiological effects of remifentanil and alfentanil in healthy volunteers. Anesthesiology 90: 718‐726, 1999.
 55. Blouin RT, Conard PF, Gross JB. Time course of ventilatory depression following induction doses of propofol and thiopental. Anesthesiology 75: 940‐944, 1991.
 56. Blouin RT, Conard PF, Perreault S, Gross JB. The effect of flumazenil on midazolam‐induced depression of the ventilatory response to hypoxia during isohypercarbia. Anesthesiology 78: 635‐641, 1993.
 57. Blouin RT, Seifert HA, Babenco HD, Conard PF, Gross JB. Propofol depresses the hypoxic ventilatory response during conscious sedation and isohypercapnia. Anesthesiology 79: 1177‐1182, 1993.
 58. Bonora M, St John WM, Bledsoe TA. Differential elevation by protriptyline and depression by diazepam of upper airway respiratory motor activity. Am Rev Respir Dis 131: 41‐45, 1985.
 59. Borgbjerg FM, Nielsen K, Franks J. Experimental pain stimulates respiration and attenuates morphine‐induced respiratory depression: A controlled study in human volunteers. Pain 64: 123‐128, 1996.
 60. Bouillon T, Bruhn J, Radu‐Radulescu L, Andresen C, Cohane C, Shafer SL. A model of the ventilatory depressant potency of remifentanil in the non‐steady state. Anesthesiology 99: 779‐787, 2003.
 61. Bouillon T, Bruhn J, Radu‐Radulescu L, Andresen C, Cohane C, Shafer SL. Mixed‐effects modeling of the intrinsic ventilatory depressant potency of propofol in the non‐steady state. Anesthesiology 100: 240‐250, 2004.
 62. Bouillon T, Bruhn J, Roepcke H, Hoeft A. Opioid‐induced respiratory depression is associated with increased tidal volume variability. Eur J Anaesthesiol 20: 127‐133, 2003.
 63. Bouillon T, Schmidt C, Garstka G, Heimbach D, Stafforst D, Schwilden H, Hoeft A. Pharmacokinetic‐pharmacodynamic modeling of the respiratory depressant effect of alfentanil. Anesthesiology 91: 144‐155, 1999.
 64. Bourke D, Malit LA, Smith TC. Respiratory interactions of ketamine and morphine. Anesthesiology 66: 153‐156, 1987.
 65. Bourke DL, Warley A. The steady‐state and rebreathing methods compared during morphine administration in humans. J Physiol 419: 509‐517, 1989.
 66. Bovill JG. Pharmacokinetics of opioids. In: Bowdle TA, Horita A, Kharasch ED, editors. The Pharmacologic Basis of Anesthesiology, New York: Churchill Livingston, 1994, pp. 37‐38.
 67. Bovill JG, Sebel PS, Blackburn CL, Oei‐Lim V, Heykants JJ. The pharmacokinetics of sufentanil in surgical patients. Anesthesiology 61: 502‐506, 1984.
 68. Brandes IF, Stuth EAE, Stucke AG, Hopp FA, Sanchez A, Zuperku EJ. Endogenous glutamatergic drive to hypoglossal motoneurons is mediated by NMDA and AMPA receptors in adult dogs in vivo. ASA 2006 Annual Meeting, Chicago, Illinois, 2006.
 69. Brandes IF, Zuperku EJ, Dean C, Hopp FA, Jakovcevic D, Stuth EA. Retrograde labeling reveals extensive distribution of genioglossal motoneurons possessing 5‐HT(2A) receptors throughout the hypoglossal nucleus of adult dogs. Brain Res 1132: 110‐119, 2007.
 70. Brandes IF, Zuperku EJ, Stucke AG, Hopp FA, Jakovcevic D, Stuth EA. Isoflurane depresses the response of inspiratory hypoglossal motoneurons to serotonin in vivo. Anesthesiology 106: 736‐745, 2007.
 71. Brandes IF, Zuperku EJ, Stucke AG, Jakovcevic D, Hopp FA, Stuth EA. Serotonergic modulation of inspiratory hypoglossal motoneurons in decerebrate dogs. J Neurophysiol 95: 3449‐3459, 2006.
 72. Brickley SG, Cull‐Candy SG, Farrant M. Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors. J Physiol 497: 753‐759, 1996.
 73. Brickley SG, Cull‐Candy SG, Farrant M. Single‐channel properties of synaptic and extrasynaptic GABAA receptors suggest differential targeting of receptor subtypes. J Neurosci 19: 2960‐2973, 1999.
 74. Brown K. Can a difference in chest wall mechanics explain the lower respiratory drive during propofol versus halothane anesthesia in children? Pediatr Pulmonol 26: 183‐189, 1998.
 75. Brown K, Aun C, Stocks J, Jackson E, Mackersie A, Hatch D. A comparison of the respiratory effects of sevoflurane and halothane in infants and young children. Anesthesiology 89: 86‐92, 1998.
 76. Brown KA, Laferriere A, Lakheeram I, Moss IR. Recurrent hypoxemia in children is associated with increased analgesic sensitivity to opiates. Anesthesiology 105: 665‐669, 2006.
 77. Brown KA, Laferriere A, Moss IR. Recurrent hypoxemia in young children with obstructive sleep apnea is associated with reduced opioid requirement for analgesia. Anesthesiology 100: 806‐810; discussion 805A, 2004.
 78. Brunner MD, Braithwaite P, Jhaveri R, McEwan AI, Goodman DK, Smith LR, Glass PS. MAC reduction of isoflurane by sufentanil. Br J Anaesth 72: 42‐46, 1994.
 79. Calverley RK, Smith NT, Jones CW, Prys‐Roberts C, Eger En. Ventilatory and cardiovascular effects of enflurane anesthesia during spontaneous ventilation in man. Anesth Analg 57: 610‐618, 1978.
 80. Campagna JA, Miller KW, Forman SA. Mechanisms of actions of inhaled anesthetics. N Engl J Med 348: 2110‐2124, 2003.
 81. Camporesi EM, Nielsen CH, Bromage PR, Durant PA. Ventilatory CO2 sensitivity after intravenous and epidural morphine in volunteers. Anesth Analg 62: 633‐640, 1983.
 82. Canet J, Sanchis J, Vila P, Zegri A, Llubia C, Vidal F. Ventilatory compensation for inspiratory resistive loads during anaesthesia with halothane or isoflurane. Br J Anaesth 82: 847‐851, 1999.
 83. Canet J, Sanchis J, Zegri A, Llorente C, Navajas D, Casan P. Effects of halothane and isoflurane on ventilation and occlusion pressure. Anesthesiology 81: 563‐571, 1994.
 84. Carlson BX, Hales TG, Olsen RW. GABAA receptors and anesthesia. In: Yaksh TL, Lynch III C, Zapol WM, Maze M, Biebuyck JF, Saidman LJ, editors. Anesthesia. Biologic Foundations (1st ed). Philadelphia: Lippincott‐Raven Publishers, 1997, pp. 259‐275.
 85. Cartwright CR, Henson LC, Ward DS. Effects of alfentanil on the ventilatory response to sustained hypoxia. Anesthesiology 89: 612‐619, 1998.
 86. Cartwright P, Prys‐Roberts C, Gill K, Dye A, Stafford M, Gray A. Ventilatory depression related to plasma fentanyl concentrations during and after anesthesia in humans. Anesth Analg 62: 966‐974, 1983.
 87. Caruso AL, Bouillon TW, Schumacher PM, Morari M. On the modeling of drug induced respiratory depression in the non‐steady‐state. Conf Proc IEEE Eng Med Biol Soc 2008: 5564‐5568, 2008.
 88. Chamberlin NL. Functional organization of the parabrachial complex and intertrigeminal region in the control of breathing. Respir Physiol Neurobiol 143: 115‐125, 2004.
 89. Chamberlin NL, Saper CB. A brainstem network mediating apneic reflexes in the rat. J Neurosci 18: 6048‐6056, 1998.
 90. Charlesworth P, Jacobson I, Richards CD. Pentobarbitone modulation of NMDA receptors in neurones isolated from the rat olfactory brain. Br J Pharmacol 116: 3005‐3013, 1995.
 91. Chatterjee IB, Majumder AK, Nandi BK, Subramanian N. Synthesis and some major functions of vitamin C in animals. Ann N Y Acad Sci 258: 24‐47, 1975.
 92. Chawla G, Drummond GB. Fentanyl decreases end‐expiratory lung volume in patients anaesthetized with sevoflurane. Br J Anaesth 100: 411‐414, 2008.
 93. Chen T, Hui R, Dong YX, Li YQ, Mizuno N. Endomorphin 1‐ and endomorphin 2‐like immunoreactive neurons in the hypothalamus send axons to the parabrachial nucleus in the rat. Neurosci Lett 357: 139‐142, 2004.
 94. Cheng G, Kendig JJ. Enflurane directly depresses glutamate AMPA and NMDA currents in mouse spinal cord motor neurons independent of actions on GABAA or glycine receptors. Anesthesiology 93: 1075‐1084, 2000.
 95. Cheng G, Kendig JJ. Enflurane decreases glutamate neurotransmission to spinal cord motor neurons by both pre‐ and postsynaptic actions. Anesth Analg 96: 1354‐1359, 2003.
 96. Chitravanshi VC, Sapru HN. NMDA as well as non‐NMDA receptors mediate the neurotransmission of inspiratory drive to phrenic motoneurons in the adult rat. Brain Res 715: 104‐112, 1996.
 97. Choi HS, Shin HC, Khang G, Rhee JM, Lee HB. Quantitative analysis of fentanyl in rat plasma by gas chromatography with nitrogen‐phosphorus detection. J Chromatogr B Biomed Sci Appl 765: 63‐69, 2001.
 98. Choi SD, Spaulding BC, Gross JB, Apfelbaum JL. Comparison of the ventilatory effects of etomidate and methohexital. Anesthesiology 62: 442‐447, 1985.
 99. Clancy B, Finlay BL, Darlington RB, Anand KJ. Extrapolating brain development from experimental species to humans. Neurotoxicology 28: 931‐937, 2007.
 100. Cleton A, Mazee D, Voskuyl RA, Danhof M. Rate of change of blood concentrations is a major determinant of the pharmacodynamics of midazolam in rats. Br J Pharmacol 127: 227‐235, 1999.
 101. Colvin MP, Savege TM, Newland PE, Weaver EJ, Waters AF, Brookes JM, Inniss R. Cardiorespiratory changes following induction of anaesthesia with etomidate in patients with cardiac disease. Br J Anaesth 51: 551‐556, 1979.
 102. Curtis JL, Lampe GH, Stulbarg MS. Mediastinal mass and tracheal obstruction during general anesthesia. Mayo Clin Proc 64: 475‐476, 1989.
 103. Dahan A, DeGoede J, Berkenbosch A, Olievier ICW. The influence of oxygen on the ventilatory response to carbon dioxide in man. J Physiol (London) 428: 485‐499, 1990.
 104. Dahan A, Kest B, Waxman AR, Sarton E. Sex‐specific responses to opiates: Animal and human studies. Anesth Analg 107: 83‐95, 2008.
 105. Dahan A, Nieuwenhuijs D, Olofsen E, Sarton E, Romberg R, Teppema L. Response surface modeling of alfentanil‐sevoflurane interaction on cardiorespiratory control and bispectral index. Anesthesiology 94: 982‐991, 2001.
 106. Dahan A, Olievier ICW, Berkenbosch A, De Goede J. Modeling the Dynamic Ventilatory Response to Carbon Dioxide in Healthy Human Subjects During Normoxia. in: “Respiratory Control: A Modelling Perspective,” G.D. Swanson and F.S. Grodins, eds. Plenum Publishing Corporation, 1989, pp. 265‐273.
 107. Dahan A, Romberg R, Sarton E, Teppema L. Antioxidants prevent blunting of hypoxic ventilatory response by low‐dose halothane. Adv Exp Med Biol 551: 217‐220, 2004.
 108. Dahan A, Romberg R, Sarton E, Teppema LJ. The Influence of Inhalational Anesthetics on Carotid Body Chemoreceptor Mediated Ventilatory Responses. In: Ward DS, Dahan A, Teppema LJ, editors. Pharmacology and Pathophysiology of the Control of Breathing. Boca Raton: Taylor and Francis, chap. 16, 2005, pp. 653‐687.
 109. Dahan A, Sarton E, Teppema L, Cees O, Niewenhuijs D, Matthes HWD, Kieffer BL. Anesthetic potency and influence of morphine and sevoflurane on respiration in μ‐opioid receptor knockout mice. Anesthesiology 94: 824‐832, 2001.
 110. Dahan A, Sarton E, Teppema L, Olievier C. Sex‐related differences in the influence of morphine on ventilatory control in humans. Anesthesiology 88: 903‐913, 1998.
 111. Dahan A, Sarton E, van den Elsen M, van Kleef J, Teppema L, Berkenbosch A. Ventilatory response to hypoxia in humans. Influences of subanesthetic desflurane. Anesthesiology 85: 60‐68, 1996.
 112. Dahan A, Teppema L. Influence of low‐dose anaesthetic agents on ventilatory control: Where do we stand? Br J Anaesth 83: 199‐201, 1999.
 113. Dahan A, Teppema LJ. Influence of anaesthesia and analgesia on the control of breathing. Br J Anaesth 91: 40‐49, 2003.
 114. Dahan A, van den Elsen MJLJ, Berkenbosch A, DeGoede J, Olievier ICW, Burm AGL, van Kleef JW. Influence of a subanesthetic concentration halothane on the ventilatory response to step changes into and out of sustained isocapnic hypoxia in healthy volunteers. Anesthesiology 81: 850‐859, 1994.
 115. Dahan A, van den Elsen MJLJ, Berkenbosch A, DeGoede J, Olievier ICW, van Kleef JW, Bovill JG. Effects of subanesthetic halothane on the ventilatory response to hypercapnia and acute hypoxia in healthy volunteers. Anesthesiology 80: 727‐738, 1994.
 116. Dahan A, Ward DS. Effect of i.v. midazolam on the ventilatory response to sustained hypoxia in man. Br J Anaesth 66: 454‐457, 1991.
 117. Dahan A, Yassen A, Bijl H, Romberg R, Sarton E, Teppema L, Olofsen E, Danhof M. Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats. Br J Anaesth 94: 825‐834, 2005.
 118. Davies RO, Edwards MW, Lahiri S. Halothane depresses the response of the carotid body chemoreceptor to hypoxia and hyperoxia in the cat. Anesthesiology 57: 153‐159, 1982.
 119. Daykin AP, Bowen DJ, Saunders DA, Norman J. Respiratory depression after morphine in the elderly. A comparison with younger subjects. Anaesthesia 41: 910‐914, 1986.
 120. De Paepe P, Belpaire FM, Rosseel MT, Van Hoey G, Boon PA, Buylaert WA. Influence of hypovolemia on the pharmacokinetics and the electroencephalographic effect of propofol in the rat. Anesthesiology 93: 1482‐1490, 2000.
 121. de Sousa SLM, Dickinson R, Lieb WR, Franks NP. Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon. Anesthesiology 92: 1055‐1066, 2000.
 122. De Troyer A, Kirkwood PA, Wilson TA. Respiratory action of the intercostal muscles. Physiol Rev 85: 717‐756, 2005.
 123. DeGoede J, Berkenbosch A, Ward DS, Bellville JW, Olievier CN. Comparison of chemoreflex gains obtained with two different methods in cats. J Appl Physiol 59 (1): 170‐179, 1985.
 124. Del Negro CA, Morgado‐Valle C, Hayes JA, Mackay DD, Pace RW, Crowder EA, Feldman JL. Sodium and calcium current‐mediated pacemaker neurons and respiratory rhythm generation. J Neurosci 25: 446‐453, 2005.
 125. Delaney AJ, Sah P. GABA receptors inhibited by benzodiazepines mediate fast inhibitory transmission in the central amygdala. J Neurosci 19: 9698‐9704, 1999.
 126. Denavit‐Saubie M, Champagnat J, Zieglgansberger W. Effects of opiates and methionine‐enkephalin on pontine and bulbar respiratory neurones of the cat. Brain Res 155: 55‐67, 1978.
 127. Derenne JP, Couture J, Iscoe S, Whitelaw A, Milic‐Emili J. Occlusion pressures in men rebreathing CO2 under methoxyflurane anesthesia. J Appl Physiol 40: 805‐814, 1976.
 128. Dhonneur G, Combes X, Leroux B, Duvaldestin P. Postoperative obstructive apnea. Anesth Analg 89: 762‐767, 1999.
 129. Dildy‐Mayfield JE, Eger EI II, Harris RA. Anesthetics produce subunit‐selective actions on glutamate receptors. J Pharmacol Exp Therapeutics 276: 1058‐1065, 1996.
 130. Ding YQ, Kaneko T, Nomura S, Mizuno N. Immunohistochemical localization of mu‐opioid receptors in the central nervous system of the rat. J Comp Neurol 367: 375‐402, 1996.
 131. Dirksen MS, Vree TB, Driessen JJ. Midazolam in the intensive care unit. Drug Intell Clin Pharm 20: 805‐806, 1986.
 132. Dogas Z, Krolo M, Stuth EA, Tonkovic‐Capin M, Hopp FA, McCrimmon DR, Zuperku EJ. Differential effects of GABAA receptor antagonists in the control of respiratory neuronal discharge patterns. J Neurophysiol 80: 2368‐2377, 1998.
 133. Dogas Z, Stuth EAE, Hopp FA, McCrimmon DR, Zuperku EJ. NMDA receptor‐mediated transmission of carotid body chemoreceptor input to expiratory bulbospinal neurones in dogs. J Physiol (London) 487: 639‐651, 1995.
 134. Doi K, Kasaba T, Kosaka Y. A comparative study of the depressive effects of halothane and sevoflurane on medullary respiratory neuron in cats. MASUI 37: 1466‐1477, 1988.
 135. Doi M, Ikeda K. Respiratory effects of sevoflurane. Anesth Analg 66: 241‐244, 1987.
 136. Dong XP, Xu TL. The action of propofol on gamma‐aminobutyric acid‐A and glycine receptors in acutely dissociated spinal dorsal horn neurons of the rat. Anesth Analg 95: 907‐914, 2002.
 137. Downie DL, Hall AC, Lieb WR, Franks NP. Effects of inhalational anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes. Br J Pharmacol 118: 493‐502, 1996.
 138. Dreixler JC, Jenkins A, Cao YJ, Roizen JD, Houamed KM. Patch‐clamp analysis of anesthetic interactions with recombinant SK2 subtype neuronal calcium‐activated potassium channels. Anesth Analg 90: 727‐732, 2000.
 139. Drolet B, Zhang S, Deschenes D, Rail J, Nadeau S, Zhou Z, January CT, Turgeon J. Droperidol lengthens cardiac repolarization due to block of the rapid component of the delayed rectifier potassium current. J Cardiovasc Electrophysiol 10: 1597‐1604, 1999.
 140. Drummond GB. Comparison of decreases in ventilation caused by enflurane and fentanyl during anaesthesia. Br J Anaesth 55: 825‐835, 1983.
 141. Drummond GB. Reduction of tonic ribcage muscle activity by anesthesia with thiopental. Anesthesiology 67: 695‐700, 1987.
 142. Drummond GB. Influence of thiopentone on upper airway muscles. Br J Anaesth 63: 12‐21, 1989.
 143. Drummond GB. “Keep a clear airway”. Br J Anaesth 66: 153‐156, 1991.
 144. Drummond GB. Comparison of sedation with midazolam and ketamine: Effects on airway muscle activity. Br J Anaesth 76: 663‐667, 1996.
 145. Drummond GB. Controlling the airway: Skill and science. Anesthesiology 97: 771‐773, 2002.
 146. Drummond GB. The abdominal muscles in anaesthesia and after surgery. Br J Anaesth 91: 73‐80, 2003.
 147. Drummond GB, Duncan MK. Abdominal pressure during laparoscopy: Effects of fentanyl. Br J Anaesth 88: 384‐388, 2002.
 148. Drummond JC. MAC for halothane, enflurane, and isoflurane in the New Zealand white rabbit: And a test for the validity of MAC determinations. Anesthesiology 62: 336‐338, 1985.
 149. Duffin J. Measuring the ventilatory response to hypoxia. J Physiol 584: 285‐293, 2007.
 150. Duffin J, Triscoll A, Whitwam JG. The effect of halothane and thiopentone on ventilatory responses mediated by the peripheral chemoreceptors in man. Br J Anaesth 48: 975‐961, 1976.
 151. Dutschmann M, Herbert H. NMDA and GABAA receptors in the rat Kolliker‐Fuse area control cardiorespiratory responses evoked by trigeminal ethmoidal nerve stimulation. J Physiol 510 (Pt 3): 793‐804, 1998.
 152. Dutschmann M, Wilson RJ, Paton JF. Respiratory activity in neonatal rats. Auton Neurosci 84: 19‐29, 2000.
 153. Duvaldestin P, Henzel D. Binding of tubocurarine, fazadinium, pancuronium and Org NC 45 to serum proteins in normal man and in patients with cirrhosis. Br J Anaesth 54: 513‐516, 1982.
 154. Dwyer R, Benett HL, Eger En, Heilbron D. Effects of isoflurane and nitrous oxide in subanesthetic concentrations on memory and responsiveness in volunteers. Anesthesiology 77: 888‐898, 1992.
 155. Dwyer R, Bennett HL, Eger EI 2nd, Peterson N. Isoflurane anesthesia prevents unconscious learning. Anesth Analg 75: 107‐112, 1992.
 156. Easton PA, Slykerman LJ, Anthonisen NR. Ventilatory response to sustained hypoxia in normal adults. J Appl Physiol 61: 906‐911, 1986.
 157. Eastwood PR, Platt PR, Shepherd K, Maddison K, Hillman DR. Collapsibility of the upper airway at different concentrations of propofol anesthesia. Anesthesiology 103: 470‐477, 2005.
 158. Eastwood PR, Szollosi I, Platt PR, Hillman DR. Collapsibility of the upper airway during anesthesia with isoflurane. Anesthesiology 97: 786‐793, 2002a.
 159. Eastwood PR, Szollosi I, Platt PR, Hillman DR. Comparison of upper airway collapse during general anaesthesia and sleep. Lancet 359: 1207‐1209, 2002b.
 160. Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 93: 382‐394, 2000.
 161. Ebert TJ, Muzi M, Berens R, Goff D, Kampine JP. Sympathetic responses to induction of anesthesia in humans with propofol or etomidate. Anesthesiology 76: 725‐733, 1992.
 162. Egan TD, Minto CF, Hermann DJ, Barr J, Muir KT, Shafer SL. Remifentanil versus alfentanil: Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers. Anesthesiology 84: 821‐833, 1996.
 163. Eger E. A brief history of the origin of minimum alveolar concentration (MAC). Anesthesiology 96: 238‐239, 2002.
 164. Eger EI 2nd, Fisher DM, Dilger JP, Sonner JM, Evers A, Franks NP, Harris RA, Kendig JJ, Lieb WR, Yamakura T. Relevant concentrations of inhaled anesthetics for in vitro studies of anesthetic mechanisms. Anesthesiology 94: 915‐921, 2001.
 165. Eger EI 2nd, Raines DE, Shafer SL, Hemmings HC Jr., Sonner JM. Is a new paradigm needed to explain how inhaled anesthetics produce immobility? Anesth Analg 107: 832‐848, 2008.
 166. Eger EI II. Isoflurane: A review. Anesthesiology 55 (5): 559‐576, 1981.
 167. Eger EI II, Dolan WM, Stevens WC, Miller RD, Way WL. Surgical stimulation antagonizes the respiratory depression produced by forane. Anesthesiology 36: 544‐549, 1972.
 168. Eger EI II, Saidman LJ, Brandstater B. Minimum alveolar anesthetic concentration: A standard of anesthetic potency. Anesthesiology 26 (6): 756‐763, 1965.
 169. Eguchi K, Tadaki E, Simbulan D Jr., Kumazawa T. Respiratory depression caused by either morphine microinjection or repetitive electrical stimulation in the region of the nucleus parabrachialis of cats. Pflugers Arch 409: 367‐373, 1987.
 170. Elliott JR, Elliott AA, Harper AA, Winpenny JP. Effects of general anaesthetics on neuronal sodium and potassium channels. Gen Pharmacol 23: 1005‐1011, 1992.
 171. Eriksson LI. The effects of residual neuromuscular blockade and volatile anesthetics on the control of ventilation. Anesth Analg 89: 243‐251, 1999.
 172. Eriksson LI, Lennmarken C, Wyon N, Johnson A. Attenuated ventilatory response to hypoxaemia at vecuronium‐induced partial neuromuscular block. Acta Anaesthesiol Scand 36: 710‐715, 1992.
 173. Eriksson LI, Sato M, Severinghaus JW. Effect of a vecuronium‐induced partial neuromuscular block on hypoxic ventilatory response. Anesthesiology 78: 693‐699, 1993.
 174. Ewen A, Archer DP, Samanani N, Roth SH. Hyperalgesia during sedation: Effects of barbiturates and propofol in the rat. Can J Anaesth 42: 532‐540, 1995.
 175. Farber NE, Pagel PS, Warltier DC. Pulmonary Pharmacology. In: Miller RD, editor. Miller's Anesthesia (5th ed). New York: Churchill Livingstone, 2000, pp. 125‐146.
 176. Feldman JL, Del Negro CA. Looking for inspiration: New perspectives on respiratory rhythm. Nat Rev Neurosci 7: 232‐242, 2006.
 177. Ferguson LM, Drummond GB. Acute effects of fentanyl on breathing pattern in anaesthetized subjects. Br J Anaesth 96: 384‐390, 2006.
 178. Fierobe L, Cantineau JP, Pandele G, Desmonts JM. Measurement of respiratory effects of propofol by indirect spirometry. Ann Fr Anesth Reanim 10: 10‐15, 1991.
 179. Flogel CM, Ward DS, Wada DR, Ritter JW. The effects of large‐dose flumazenil on midazolam‐induced ventilatory depression. Anesth Analg 77: 1207‐1214, 1993.
 180. Flood P, Coates KM. Sensitivity of the alpha7 nicotinic acetylcholine receptor to isoflurane may depend on receptor inactivation. Anesth Analg 95: 83‐87, 2002.
 181. Flood P, Krasowski MD. Intravenous anesthetics differentially modulate ligand‐gated ion channels. Anesthesiology 92: 1418‐1425, 2000.
 182. Flood P, Ramirez‐Latorre J, Role L. Alpha4beta2 neuronal nicotinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but alpha7‐type nicotinic acetylcholine receptors are unaffected. Anesthesiology 86: 859‐865, 1997.
 183. Foldes FF, Deery A. Protein binding of atracurium and other short‐acting neuromuscular blocking agents and their interaction with human cholinesterases. Br J Anaesth 55 (Suppl 1): 31S‐34S, 1983.
 184. Forster A, Crettenand G, Klopfenstein CE, Morel DR. Absence of agonist effects of high‐dose flumazenil on ventilation and psychometric performance in human volunteers. Anesth Analg 77: 980‐984, 1993.
 185. Forster HV, Martino P, Hodges M, Krause K, Bonis J, Davis S, Pan L. The carotid chemoreceptors are a major determinant of ventilatory CO2 sensitivity and of PaCO2 during eupneic breathing. Adv Exp Med Biol 605: 322‐326, 2008.
 186. Fortuna MG, West GH, Stornetta RL, Guyenet PG. Botzinger expiratory‐augmenting neurons and the parafacial respiratory group. J Neurosci 28: 2506‐2515, 2008.
 187. Fourcade HE, Stevens WC, Larson CP Jr., Cromwell TH, Bahlman SH, Hickey RF, Halsey MJ, Eger EI II. The ventilatory effects of forane*, a new inhaled anesthetic. Anesthesiology 35: 26‐31, 1971.
 188. Foutz AS, Champagnat J, Denavit‐Saubie M. N‐methyl‐D‐aspartate (NMDA) receptors control respiratory off‐switch in cat. NeurosciLett 87: 221‐226, 1988.
 189. Foutz AS, Pierrefiche O, Denavit‐Saubié M. Combined blockade of NMDA and non‐NMDA receptors produces respiratory arrest in the adult cat. NeuroReport 5: 481‐484, 1994.
 190. Fragen RJ, Avram MJ, Henthorn TK, Caldwell NJ. A pharmacokinetically designed etomidate infusion regimen for hypnosis. Anesth Analg 62: 654‐660, 1983.
 191. Franks NP. Molecular targets underlying general anaesthesia. Br J Pharmacol 147 (Suppl 1): S72‐S81, 2006.
 192. Franks NP. General anaesthesia: From molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci 9: 370‐386, 2008.
 193. Franks NP, Dickinson R, de Sousa SL, Hall AC, Lieb WR. How does xenon produce anesthesia? Nature 396: 324, 1998.
 194. Franks NP, Honore E. The TREK K2P channels and their role in general anaesthesia and neuroprotection. Trends Pharmacol Sci 25: 601‐608, 2004.
 195. Franks NP, Lieb WR. Anaesthetics set their sites on ion channels. Nature 389: 334‐335, 1997.
 196. Franks NP, Lieb WR. Volatile general anaesthetics activate a novel K+ current. Nature 333: 662‐664, 1988.
 197. Franks NP, Lieb WR. Temperature dependence of the potency of volatile anesthetics: Implications for in vitro experiments. Anesthesiology 84: 716‐720, 1996.
 198. Franks NP, Lieb WR. Which molecular targets are most relevant to general anaesthesia? Toxicol Lett 100‐101: 1‐8, 1998.
 199. Freund F, Roos A, Dodd RB. Expiratory activity of the abdominal muscles in man during general anasthesia. J Appl Physiol 19: 693‐697, 1964.
 200. Freund FG, Martin WE, Wong KC, Hornbein TF. Abdominal‐muscle rigidity induced by morphine and nitrous oxide. Anesthesiology 38: 358‐362, 1973.
 201. Friederich P, Urban BW. Interaction of intravenous anesthetics with human neuronal potassium currents in relation to clinical concentrations. Anesthesiology 91: 1853‐1860, 1999.
 202. Gage PW, Robertson B. Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA1 pyramidal cells in rat hippocampus. Br J Pharmacol 85: 675‐681, 1985.
 203. Gal TJ, DiFazio CA, Moscicki J. Analgesic and respiratory depressant activity of nalbuphine: A comparison with morphine. Anesthesiology 57: 367‐374, 1982.
 204. Garton KJ, Yuen P, Meinwald J, Thummel KE, Kharasch ED. Stereoselective metabolism of enflurane by human liver cytochrome P450 2E1. Drug Metab Dispos 23: 1426‐1430, 1995.
 205. Gautier H. Pattern of breathing during hypoxia or hypercapnia of the awake or anesthetized cat. Resp Physiol 27: 193‐206, 1976.
 206. Gautier H. Hypoxia, hyperoxia and breathing. J Biosci 31: 185‐190, 2006.
 207. Gautier H, Bonora M, Zaoui D. Influence of halothane on control of breathing in intact and decerebrated cats. JApplPhysiol 63 (2): 546‐553, 1987.
 208. Gautier H, Offenstadt G, Kaczmarek R, Bonora M, Pinta P, Hericoard P. Pattern of respiration in patients recovering from barbiturate overdose. Br J Anaesth 54: 1041‐1045, 1982.
 209. Glare PA, Walsh TD. Clinical pharmacokinetics of morphine. Ther Drug Monit 13: 1‐23, 1991.
 210. Glass PS, Iselin‐Chaves IA, Goodman D, Delong E, Hermann DJ. Determination of the potency of remifentanil compared with alfentanil using ventilatory depression as the measure of opioid effect. Anesthesiology 90: 1556‐1563, 1999.
 211. Gonzales JM, Loeb AL, Reichard PS, Irvine S. Ketamine inhibits glutamate‐, N‐methyl‐D‐aspartate‐. and quisqualate‐stimulated cGMP production in cultured cerebral neurons. Anesthesiology 82: 205‐213, 1995.
 212. Goodman NW. Volatile agents and the ventilatory response to hypoxia. Editorial. BrJAnaesth 72: 503‐505, 1994.
 213. Goodman NW, Black AM, Carter JA. Some ventilatory effects of propofol as sole anaesthetic agent. Br J Anaesth 59: 1497‐1503, 1987.
 214. Goodman NW, Curnow JS. The ventilatory response to carbon dioxide. An analysis of data obtained by the rebreathing method. Br J Anaesth 57: 311‐318, 1985.
 215. Gourine AV. On the peripheral and central chemoreception and control of breathing: An emerging role of ATP. J Physiol 568: 715‐724, 2005.
 216. Grabowska‐Gawel A. End‐tidal sevoflurane concentrations for laryngeal mask airway insertion and tracheal intubation in children. Przegl Lek 61: 783‐785, 2004.
 217. Graham SG. New drug in volatile anaesthesia–desflurane. Ann Acad Med Singapore 23: 510‐518, 1994.
 218. Grasshoff C, Antkowiak B. Propofol and sevoflurane depress spinal neurons in vitro via different molecular targets. Anesthesiology 101: 1167‐1176, 2004.
 219. Grasshoff C, Antkowiak B. Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats. Br J Anaesth 97: 687‐694, 2006.
 220. Grasshoff C, Rudolph U, Antkowiak B. Molecular and systemic mechanisms of general anaesthesia: The ‘multi‐site and multiple mechanisms' concept. Curr Opin Anaesthesiol 18: 386‐391, 2005.
 221. Grassino AE, Derenne JP, Almirall J, Milic‐Emili J, Whitelaw W. Configuration of the chest wall and occlusion pressures in awake humans. J Appl Physiol 50: 134‐142, 1981.
 222. Graves DA, Arrigo JM, Foster TS, Baumann TJ, Batenhorst RL. Relationship between plasma morphine concentrations and pharmacologic effects in postoperative patients using patient‐controlled analgesia. Clin Pharm 4: 41‐47, 1985.
 223. Gray AC, Coupar IM, White PJ. Comparison of opioid receptor distributions in the rat central nervous system. Life Sci 79: 674‐685, 2006.
 224. Gray PA, Rekling JC, Bocchiaro CM, Feldman JL. Modulation of respiratory frequency by peptidergic input to rhythmogenic neurons in the preBötzinger complex. Science 286: 1566‐1568, 1999.
 225. Green WBJ. The ventilatory effects of sevoflurane. Anesth Analg 81: S23‐S26, 1995.
 226. Greenblatt DJ, Ehrenberg BL, Culm KE, Scavone JM, Corbett KE, Friedman HL, Harmatz JS, Shader RI. Kinetics and EEG effects of midazolam during and after 1‐minute, 1‐hour, and 3‐hour intravenous infusions. J Clin Pharmacol 44: 605‐611, 2004.
 227. Greenwell TN, Martin‐Schild S, Inglis FM, Zadina JE. Colocalization and shared distribution of endomorphins with substance P, calcitonin gene‐related peptide, gamma‐aminobutyric acid, and the mu opioid receptor. J Comp Neurol 503: 319‐333, 2007.
 228. Grelot L, Bianchi AL. Differential effects of halothane anesthesia on the pattern of discharge of inspiratory and expiratory neurons in the region of the retrofacial nucleus. Brain Res 404: 335‐338, 1987.
 229. Gross JB. Resting ventilation measurements may be misleading. Anesthesiology 61: 110, 1984.
 230. Gross JB. When you breathe IN you inspire, when you DON'T breathe, you…expire: New insights regarding opioid‐induced ventilatory depression. Anesthesiology 99: 767‐770, 2003.
 231. Gross JB. Ventilatory effects of medications used for moderate and deep sedation. In: Denham S, Ward AD, Teppema LJ, editors. Pharmacology and Pathophysiology ot the Control of Breathing. Boca Raton, FL: Taylor and Francis Group, LLC, 2005, pp. 513‐570.
 232. Gross JB, Blouin RT, Zandsberg S, Conard PF, Haussler J. Effect of flumazenil on ventilatory drive during sedation with midazolam and alfentanil. Anesthesiology 85: 713‐720, 1996.
 233. Gross JB, Weller RS, Conard P. Flumazenil antagonism of midazolam‐induced ventilatory depression. Anesthesiology 75: 179‐185, 1991.
 234. Gross JB, Zebrowski ME, Carel WD, Gardner S, Smith TC. Time course of ventilatory depression after thiopental and midazolam in normal subjects and in patients with chronic obstructive pulmonary disease. Anesthesiology 58: 540‐544, 1983.
 235. Grounds RM, Maxwell DL, Taylor MB, Aber V, Royston D. Acute ventilatory changes during i.v. induction of anaesthesia with thiopentone or propofol in man. Studies using inductance plethysmography. Br J Anaesth 59: 1098‐1102, 1987.
 236. Gruss M, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP. Two‐pore‐domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol Pharmacol 65: 443‐452, 2004.
 237. Guyenet PG, Stornetta RL, Bayliss DA. Central respiratory chemoreception. J Comp Neurol 518: 3883‐3906, 2010.
 238. Guyenet PG, Stornetta RL, Bayliss DA. Retrotrapezoid nucleus and central chemoreception. J Physiol 586: 2043‐2048, 2008.
 239. Haji A, Okazaki M, Ohi Y, Yamazaki H, Takeda R. Biphasic effects of morphine on bulbar respiratory neuronal activities in decerebrate cats. Neuropharmacology 45: 368‐379, 2003.
 240. Haji A, Takeda R. Depression of respiratory‐related nerve activities by ethanol and diazepam. Arukoru Kenkyuto Yakubutsu Ison 22: 224‐233, 1987.
 241. Haji A, Takeda R, Okazaki M. Neuropharmacology of control of respiratory rhythm and pattern in mature mammals. Pharmacol Ther 86: 277‐304, 2000.
 242. Haji A, Yamazaki H, Ohi Y, Takeda R. Distribution of mu receptors in the ventral respiratory group neurons; immunohistochemical and pharmacological studies in decerebrate cats. Neurosci Lett 351: 37‐40, 2003.
 243. Hajiha M, DuBord MA, Liu H, Horner RL. Opioid receptor mechanisms at the hypoglossal motor pool and effects on tongue muscle activity in vivo. J Physiol 587: 2677‐2692, 2009.
 244. Hales TG, Lambert JJ. The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones. Br J Pharmacol 104: 619‐628, 1991.
 245. Hall AC, Lieb WR, Franks NP. Insensitivity of P‐type calcium channels to inhalational and intravenous general anesthetics. Anesthesiology 81: 117‐123, 1994a.
 246. Hall AC, Lieb WR, Franks NP. Stereoselective and nonstereoselective actions of isoflurane on the GABAA receptor. BrJPharmacol 112: 906‐910, 1994b.
 247. Hammer GB, Drover DR, Cao H, Jackson E, Williams GD, Ramamoorthy C, Van Hare GF, Niksch A, Dubin AM. The effects of dexmedetomidine on cardiac electrophysiology in children. Anesth Analg 106: 79‐83, 2008.
 248. Hammer J, Reber A, Trachsel D, Frei FJ. Effect of jaw‐thrust and continuous positive airway pressure on tidal breathing in deeply sedated infants. J Pediatr 138: 826‐830, 2001.
 249. Hamunen K. Ventilatory effects of morphine, pethidine and methadone in children. Br J Anaesth 70: 414‐418, 1993.
 250. Hamza J, Ecoffey C, Gross JB. Ventilatory response to CO2 following intravenous ketamine in children. Anesthesiology 70: 422‐425, 1989.
 251. Hansen D, Heitz E, Toussaint S, Schaffartzik W, Striebel HW. Deep halothane anaesthesia compared with halothane‐suxamethonium anaesthesia for tracheal intubation in young children. Eur J Anaesthesiol 14: 29‐34, 1997.
 252. Hara K, Harris RA. The anesthetic mechanism of urethane: The effects on neurotransmitter‐gated ion channels. Anesth Analg 94: 313‐318, 2002.
 253. Hara M, Kai Y, Ikemoto Y. Enhancement by propofol of the γ‐aminobutyric acidA response in dissociated hippocampal pyramidal neurons of the rat. Anesthesiology 81: 988‐994, 1994.
 254. Harper MH, Hickey RF, Cromwell TH, Linwood S. The magnitude and duration of respiratory depression produced by fentanyl and fentanyl plus droperidol in man. J Pharmacol Exp Ther 199: 464‐468, 1976.
 255. Hawk CT, Leary SL. Formulary for Laboratory Animals. Ames, Iowa: Iowa University Press, 1999.
 256. Heavner JE. Morphine for postsurgical use in cats. J Am Vet Med Assoc 156: 1018‐1019, 1970.
 257. Hecker KE, Horn N, Baumert JH, Reyle‐Hahn SM, Heussen N, Rossaint R. Minimum alveolar concentration (MAC) of xenon in intubated swine. Br J Anaesth 92: 421‐424, 2004.
 258. Hedenstierna G, Strandberg A, Brismar B, Lundquist H, Svensson L, Tokics L. Functional residual capacity, thoracoabdominal dimensions, and central blood volume during general anesthesia with muscle paralysis and mechanical ventilation. Anesthesiology 62: 247‐254, 1985.
 259. Heeringa J, Berkenbosch A, DeGoede J, Olievier CN. Relative contribution of central and peripheral chemoreceptors to the ventilatory response to CO2 during hyperoxia. RespirPhysiol 37: 365‐379, 1979.
 260. Hemmings HC Jr. Noble meets nouveau: A shared anesthetic binding site for xenon and isoflurane on a glutamate receptor. Anesthesiology 107: 694‐696, 2007.
 261. Hemmings HC Jr. Sodium channels and the synaptic mechanisms of inhaled anaesthetics. Br J Anaesth 103: 61‐69, 2009.
 262. Hemmings HC Jr., Akabas MH, Goldstein PA, Trudell JR, Orser BA, Harrison NL. Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol Sci 26: 503‐510, 2005.
 263. Hemmings HC Jr., Yan W, Westphalen RI, Ryan TA. The general anesthetic isoflurane depresses synaptic vesicle exocytosis. Mol Pharmacol 67: 1591‐1599, 2005.
 264. Henke KG, Sharratt M, Pegelow D, Dempsey JA. Regulation of end‐expiratory lung volume during exercise. J Appl Physiol 64: 135‐146, 1988.
 265. Hentschke H, Schwarz C, Antkowiak B. Neocortex is the major target of sedative concentrations of volatile anaesthetics: Strong depression of firing rates and increase of GABAA receptor‐mediated inhibition. Eur J Neurosci 21: 93‐102, 2005.
 266. Hickey RF, Fourcade HE, Eger EI II, Larson. CP Jr., Bahlman SH, Stevens WC, Gregory GA, Smith NT. The effects of ether, halothane, and forane on apneic thresholds in man. Anesthesiology 35: 32‐37, 1971.
 267. Hickey RF, Visick WD, Fairley HB, Fourcade HE. Effects of halothane anesthesia on functional residual capacity and alveolar‐arterial oxygen tension difference. Anesthesiology 38: 20‐24, 1973.
 268. Hilaire G, Monteau R, Errchidi S. Possible modulation of the medullary respiratory rhythm generator by the noradrenergic A5 area: An in vitro study in the newborn rat. Brain Res 485: 325‐332, 1989.
 269. Hilaire G, Viemari JC, Coulon P, Simonneau M, Bevengut M. Modulation of the respiratory rhythm generator by the pontine noradrenergic A5 and A6 groups in rodents. Respir Physiol Neurobiol 143: 187‐197, 2004.
 270. Hillman DR, Loadsman JA, Platt PR, Eastwood PR. Obstructive sleep apnoea and anaesthesia. Sleep Med Rev 8: 459‐471, 2004.
 271. Hillman DR, Platt PR, Eastwood PR. The upper airway during anaesthesia. Br J Anaesth 91: 31‐39, 2003.
 272. Hillman DR, Walsh JH, Maddison KJ, Platt PR, Kirkness JP, Noffsinger WJ, Eastwood PR. Evolution of changes in upper airway collapsibility during slow induction of anesthesia with propofol. Anesthesiology 111: 63‐71, 2009.
 273. Hirshman CA, McCullough RE, Cohen PJ, Weil JV. Hypoxic ventilatory drive in dogs during thiopental, ketamine, or pentobarbital anesthesia. Anesthesiology 43: 628‐634, 1975.
 274. Hirshman CA, McCullough RE, Cohen PJ, Weil JV. Depression of hypoxic ventilatory response by halothane, enflurane and isoflurane in dogs. Br J Anaesth 43: 957‐963, 1977.
 275. Horner RL. Neuromodulation of hypoglossal motoneurons during sleep. Respir Physiol Neurobiol 164: 179‐196, , 2008.
 276. Horner RL, Innes JA, Guz A. Reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in awake man. Sleep 16: S85‐S86, 1993.
 277. Horner RL, Innes JA, Murphy K, Guz A. Evidence for reflex upper airway dilator muscle activation by sudden negative airway pressure in man. J Physiol 436: 15‐29, 1991.
 278. Hornuss C, Praun S, Villinger J, Dornauer A, Moehnle P, Dolch M, Weninger E, Chouker A, Feil C, Briegel J, Thiel M, Schelling G. Real‐time monitoring of propofol in expired air in humans undergoing total intravenous anesthesia. Anesthesiology 106: 665‐674, 2007.
 279. Hoshino Y, Ayuse T, Kurata S, Schneider H, Kirkness JP, Patil SP, Schwartz AR, Oi K. The compensatory responses to upper airway obstruction in normal subjects under propofol anesthesia. Respir Physiol Neurobiol 166: 24‐31, 2009.
 280. Howard RS, Sears TA. The effects of opiates on the respiratory activity of thoracic motoneurones in the anaesthetized and decerebrate rabbit. J Physiol 437: 181‐199, 1991.
 281. Hsia TY, Khambadkone S, Redington AN, Migliavacca F, Deanfield JE, de Leval MR. Effects of respiration and gravity on infradiaphragmatic venous flow in normal and Fontan patients. Circulation 102: III148‐III153, 2000.
 282. Hsu YW, Cortinez LI, Robertson KM, Keifer JC, Sum‐Ping ST, Moretti EW, Young CC, Wright DR, Macleod DB, Somma J. Dexmedetomidine pharmacodynamics: Part I: Crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology 101: 1066‐1076, 2004.
 283. Hug CC. Pharmacokinetics and dynamics of narcotic analgesics. In: Prys‐Roberts C, Hug CC, editors. Pharmacokinetics of Anesthesia. London: Blackwell Scientific Publications, 1984, pp. 187‐234.
 284. Hugelin A. Forebrain and midbrain influences on respiration. In: Geiger SR, editor. Handbook of Physiology ‐ The Respiratory System (2nd ed). Bethesda: American Physiological Society, 1986, pp. 69‐91.
 285. Hung OR, Varvel JR, Shafer SL, Stanski DR. Thiopental pharmacodynamics. II. Quantitation of clinical and electroencephalographic depth of anesthesia. Anesthesiology 77: 237‐244, 1992.
 286. Hurle MA, Mediavilla A, Florez J. Participation of pontine structures in the respiratory action of opioids. Life Sci 33 (Suppl 1): 571‐574, 1983.
 287. Hurle MA, Mediavilla A, Florez J. Differential respiratory patterns induced by opioids applied to the ventral medullary and dorsal pontine surfaces of cats. Neuropharmacology 24: 597‐606, 1985.
 288. Hwang J‐C, St. John WM, Bartlett D Jr.. Respiratory‐related hypoglossal nerve activity influence of anesthetics. JApplPhysiol 55: 785‐792, 1983.
 289. Hynynen M, Hynninen M, Soini H, Neuvonen PJ, Heinonen J. Plasma concentration and protein binding of alfentanil during high‐dose infusion for cardiac surgery. Br J Anaesth 72: 571‐576, 1994.
 290. Ide T, Sakurai Y, Aono M, Nishino T. Contribution of peripheral chemoreception to the depression of the hypoxic ventilatory response during halothane anesthesia in cats. Anesthesiology 90: 1084‐1091, 1999.
 291. Ilomaki J, Baer GA, Karhuketo T, Talonen P, Puhakka H. Pharyngeal patency caused by stimulation of the hypoglossal nerve in anaesthesia‐relaxed patients. Acta Otolaryngol Suppl 529: 210‐211, 1997.
 292. Inomata S, Suwa T, Toyooka H, Suto Y. End‐tidal sevoflurane concentration for tracheal extubation and skin incision in children. Anesth Analg 87: 1263‐1267, 1998.
 293. Inomata S, Watanabe S, Taguchi M, Okada M. End‐tidal sevoflurane concentration for tracheal intubation and minimum alveolar concentration in pediatric patients. Anesthesiology 80: 93‐96, 1994.
 294. Irnaten M, Walwyn WM, Wang J, Venkatesan P, Evans C, Chang KSK, Andresen MC, Hales TG, Mendelowitz D. Pentobarbital enhances GABAergic neurotransmission to cardiac parasympathetic neurons, which is prevented by expression of GABA(A) epsilon subunit. Anesthesiology 97: 717‐724, 2002.
 295. Irnaten M, Wang J, Venkatesan P, Evans C, K Chang KS, Andresen MC, Mendelowitz D. Ketamine inhibits presynaptic and postsynaptic nicotinic excitation of identified cardiac parasympathetic neurons in nucleus ambiguus. Anesthesiology 96: 667‐674, 2002.
 296. Isaev G, Murphy K, Guz A, Adams L. Areas of the brain concerned with ventilatory load compensation in awake man. J Physiol 539: 935‐945, 2002.
 297. Isono S, Nishino T, Sugimori K, Mizuguchi T. Respiratory effects of expiratory flow‐resistive loading in conscious and anesthetized humans. Anesth Analg 70: 594‐599, 1990.
 298. Izumi H, Ito Y. Correlation between degree of inhibition of parasympathetic reflex vasodilation and MAC value for various inhalation anesthetics. Gen Parmacal 32: 689‐693, 1999.
 299. Janczewski WA, Feldman JL. Distinct rhythm generators for inspiration and expiration in the juvenile rat. J Physiol 570(Pt 2): 407‐420, 2006.
 300. Janczewski WA, Onimaru H, Homma I, Feldman JL. Opioid‐resistant respiratory pathway from the preinspiratory neurones to abdominal muscles: In vivo and in vitro study in the newborn rat. J Physiol 545(Pt 3): 1017‐1026, 2002.
 301. Jaspar N, Mazzarelli M, Tessier C, Milic‐Emili J. Effect of ketamine on control of breathing in cats. J Appl Physiol 55: 851‐859, 1983.
 302. Jewett BA, Gibbs LM, Tarasiuk A, Kendig JJ. Propofol and barbiturate depression of spinal nociceptive neurotransmission. Anesthesiology 77: 1148‐1154, 1992.
 303. Jiang ZG, North RA. Pre‐ and postsynaptic inhibition by opioids in rat striatum. J Neurosci 12: 356‐361, 1992.
 304. Jin Y‐H, Bailey TW, Doyle MW, Li B‐Y, Chang KSK, Schild JH, Mendelowitz D, Andresen MC. Ketamine differentially blocks sensory afferent synaptic transmission in medial nucleus tractus solitarius (mNTS). Anesthesiology 98: 121‐132, 2003.
 305. Joensen H, Sadler CL, Ponte J, Yamamoto Y, Lindahl SG, Eriksson LI. Isoflurane does not depress the hypoxic response of rabbit carotid body chemoreceptors. Anesth Analg 91: 480‐485, 2000.
 306. Johnson SM, Smith JC, Feldman JL. Modulation of respiratory rhythm in vitro: Role of Gi/o protein‐mediated mechanisms. J Appl Physiol 80: 2120‐2133, 1996.
 307. Jones JG, Faithfull D, Jordan C, Minty B. Rib cage movement during halothane anaesthesia in man. BrJAnaesth 51: 399‐407, 1979.
 308. Jones MV, Harrison NL. Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons. JNeurophysiol 70: 1339‐1349, 1993.
 309. Jones RM. Desflurane and sevoflurane: Inhalation anaesthetics for this decade? BrJAnaesth 65: 527‐536, 1990.
 310. Jonsson M, Wyon N, Lindahl SG, Fredholm BB, Eriksson LI. Neuromuscular blocking agents block carotid body neuronal nicotinic acetylcholine receptors. Eur J Pharmacol 497: 173‐180, 2004.
 311. Jonsson MM, Lindahl SG, Eriksson LI. Effect of propofol on carotid body chemosensitivity and cholinergic chemotransduction. Anesthesiology 102: 110‐116, 2005.
 312. Judge O, Hill S, Antognini JF. Modeling the effects of midazolam on cortical and thalamic neurons. Neurosci Lett 464: 135‐139, 2009.
 313. Kafer ER, Brown JT, Scott D, Findlay JW, Butz RF, Teeple E, Ghia JN. Biphasic depression of ventilatory responses to CO2 following epidural morphine. Anesthesiology 58: 418‐427, 1983.
 314. Kalvass JC, Olson ER, Cassidy MP, Selley DE, Pollack GM. Pharmacokinetics and pharmacodynamics of seven opioids in P‐glycoprotein‐competent mice: Assessment of unbound brain EC50,u and correlation of in vitro, preclinical, and clinical data. J Pharmacol Exp Ther 323: 346‐355, 2007.
 315. Kammer T, Rehberg B, Menne D, Wartenberg HC, Wenningmann I, Urban BW. Propofol and sevoflurane in subanesthetic concentrations act preferentially on the spinal cord: Evidence from multimodal electrophysiological assessment. Anesthesiology 97: 1416‐1425, 2002.
 316. Kanamaru M, Homma I. Dorsomedial medullary 5‐HT2 receptors mediate immediate onset of initial hyperventilation, airway dilation, and ventilatory decline during hypoxia in mice. Am J Physiol Regul Integr Comp Physiol 297: R34‐R41, 2009.
 317. Kasaba T, Kosaka Y, Doi K. A comparative study of the depressive effects of halothane and enflurane from 1 MAC to 3 MAC on medullary respiratory neuron in cats. MASUI 36 (10): 1596‐1601, 1987.
 318. Kasaba T, Takeshita M, Takasaki M. The effects of caffeine on the respiratory depression by morphine. Masui 46: 1570‐1574, 1997.
 319. Kashiwagi M, Okada Y, Kuwana S, Sakuraba S, Ochiai R, Takeda J. A neuronal mechanism of propofol‐induced central respiratory depression in newborn rats. Anesth Analg 99: 49‐55, 2004a.
 320. Kashiwagi M, Okada Y, Kuwana S, Sakuraba S, Ochiai R, Takeda J. Mechanism of propofol‐induced central respiratory depression in neonatal rats anatomical sites and receptor types of action. Adv Exp Med Biol 551: 221‐226, 2004b.
 321. Katoh T, Nakajima Y, Moriwaki G, Kobayashi S, Suzuki A, Iwamoto T, Bito H, Ikeda K. Sevoflurane requirements for tracheal intubation with and without fentanyl. Br J Anaesth 82: 561‐565, 1999.
 322. Kaufman RD, Aqleh KA, Bellville JW. Relative potencies and durations of action with respect to respiratory depression of intravenous meperidine, fentanyl and alphaprodine in man. J Pharmacol Exp Ther 208: 73‐79, 1979.
 323. Kaul SU, Heath JR, Nunn JF. Factors influencing the development of expiratory muscle activity during anaesthesia. Br J Anaesth 45: 1013‐1018, 1973.
 324. Kay B. The measurement of occlusion pressure during anaesthesia. A comparison of the depression of respiratory drive by methohexitone and etomidate. Anaesthesia 34: 543‐548, 1979.
 325. Kazama T, Takeuchi K, Ikeda K, Ikeda T, Kikura M, Iida T, Suzuki S, Hanai H, Sato S. Optimal propofol plasma concentration during upper gastrointestinal endoscopy in young, middle‐aged, and elderly patients. Anesthesiology 93: 662‐669, 2000.
 326. Kharasch ED. Biotransformation of sevoflurane. Anesth Analg 81: S27‐S38, 1995.
 327. Kharasch ED. Metabolism and toxicity of the new anesthetic agents. Acta Anaesthesiol Belg 47: 7‐14, 1996.
 328. Kharasch ED, Armstrong AS, Gunn K, Artru A, Cox K, Karol MD. Clinical sevoflurane metabolism and disposition. II. The role of cytochrome P450 2E1 in fluoride and hexafluoroisopropanol formation. Anesthesiology 82: 1379‐1388, 1995.
 329. Kharasch ED, Hankins D, Mautz D, Thummel KE. Identification of the enzyme responsible for oxidative halothane metabolism: Implications for prevention of halothane hepatitis. Lancet 347: 1367‐1371, 1996.
 330. Kharasch ED, Hankins DC, Cox K. Clinical isoflurane metabolism by cytochrome P450 2E1. Anesthesiology 90: 766‐771, 1999.
 331. Kharasch ED, Thummel KE. Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, and methoxyflurane. Anesthesiology 79: 795‐807, 1993.
 332. Kim C, Shvarev Y, Takeda S, Sakamoto A, Lindahl SG, Eriksson LI. Midazolam depresses carotid body chemoreceptor activity. Acta Anaesthesiol Scand 50: 144‐149, 2006.
 333. Kim G, Green SM, Denmark TK, Krauss B. Ventilatory response during dissociative sedation in children‐a pilot study. Acad Emerg Med 10: 140‐145, 2003.
 334. Kimura T, Watanabe S, Asakura N, Inomata S, Okada M, Taguchi M. Determination of end‐tidal sevoflurane concentration for tracheal intubation and minimum alveolar anesthetic concentration in adults. Anesth Analg 79: 378‐381, 1994.
 335. Kingery WS, Agashe GS, Guo TZ, Sawamura S, Davies MF, Clark JD, Kobilka BK, Maze M. Isoflurane and nociception: Spinal alpha2A adrenoceptors mediate antinociception while supraspinal alpha1 adrenoceptors mediate pronociception. Anesthesiology 96: 367‐374, 2002.
 336. Kira T, Harata N, Sakata T, Akaike N. Kinetics of sevoflurane action on GABA‐ and glycine‐induced currents in acutely dissociated rat hippocampal neurons. Neuroscience 85: 383‐394, 1998.
 337. Kirby GC, McQueen DS. Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo. Br J Pharmacol 88: 889‐898, 1986.
 338. Kirson ED, Yaari Y, Perouansky M. Presynaptic and postsynaptic actions of halothane at glutamatergic synapses in the mouse hippocampus. Br J Pharmacol 124: 1607‐1614, 1998.
 339. Kissin I, Morgan PL, Smith LR. Comparison of isoflurane and halothane safety margins in rats. Anesthesiology 58: 556‐561, 1983.
 340. Knill RL, Bright S, Manninen P. Hypoxic ventilatory responses during thiopentone sedation and anaesthesia in man. Can Anaesth Soc J 25: 366‐372, 1978.
 341. Knill RL, Clement JL. Site of selective action of halothane on the peripheral chemoreflex pathway in humans. Anesthesiology 61: 121‐126, 1984.
 342. Knill RL, Gelb AW. Ventilatory responses to hypoxia and hypercapnia during halothane sedation and anesthesia in man. Anesthesiology 49: 244‐251, 1978.
 343. Knill RL, Gelb AW. Editorial views: Peripheral chemoreceptors during anesthesia. Are the watchdogs sleeping? Aneesthesiology 57: 151‐152, 1982.
 344. Knill RL, Manninen P, Clement JL. Ventilation and chemoreflexes during enflurane sedation and anesthesia in man. Can Anaesth Soc J 26: 353‐360, 1979.
 345. Koh SO, Severinghaus JW. Effect of halothane on hypoxic and hypercapnic ventilatory responses of goats. BrJAnaesth 65: 713‐717, 1990.
 346. Kohno T, Ikoma M. Sudden vocal cord closure during general anesthesia using remifentanil. Masui 57: 1213‐1217, 2008.
 347. Koizumi H, Smerin SE, Yamanishi T, Moorjani BR, Zhang R, Smith JC. TASK channels contribute to the K+‐dominated leak current regulating respiratory rhythm generation in vitro. J Neurosci 30: 4273‐4284.
 348. Kong CF, Chew ST, Ip‐Yam PC. Intravenous opioids reduce airway irritation during induction of anaesthesia with desflurane in adults. Br J Anaesth 85: 364‐367, 2000.
 349. Krolo M, Stuth EA, Tonkovic‐Capin M, Dogas Z, Hopp FA, McCrimmon DR, Zuperku EJ. Differential roles of ionotropic glutamate receptors in canine medullary inspiratory neurons of the ventral respiratory group. J Neurophysiol 82: 60‐68, 1999.
 350. Krolo M, Stuth EA, Tonkovic‐Capin M, Hopp FA, McCrimmon DR, Zuperku EJ. Relative magnitude of tonic and phasic synaptic excitation of medullary inspiratory neurons in dogs. Am J Physiol Regul Integr Comp Physiol 279: R639‐R649, 2000.
 351. Kryger MH, Yacoub O, Anthonisen NR. Effect of inspiratory resistance of occlusion pressure in hypoxia and hypercapnia. Respir Physiol 24: 241‐248, 1975.
 352. Kryger MH, Yacoub O, Dosman J, Macklem PT, Anthonisen NR. Effect of meperidine on occlusion pressure responses to hypercapnia and hypoxia with and without external inspiratory resistance. Am Rev Respir Dis 114: 333‐340, 1976.
 353. Kulkarni P, Brown KA. Ventilatory parameters in children during propofol anaesthesia: A comparison with halothane. Can J Anaesth 43: 653‐659, 1996.
 354. Kulkarni RS, Zorn LJ, Anantharam V, Bayley H, Treistman SN. Inhibitory effects of ketamine and halothane on recombinant potassium channels from mammalian brain. Anesthesiology 84: 900‐909, 1999.
 355. Kullmann DM, Ruiz A, Rusakov DM, Scott R, Semyanov A, Walker MC. Presynaptic, extrasynaptic and axonal GABAA receptors in the CNS: Where and why? Prog Biophys Mol Biol 87: 33‐46, 2005.
 356. Kuribayashi J, Sakuraba S, Kashiwagi M, Hatori E, Tsujita M, Hosokawa Y, Takeda J, Kuwana S. Neural mechanisms of sevoflurane‐induced respiratory depression in newborn rats. Anesthesiology 109: 233‐242, 2008.
 357. Laferriere A, Liu JK, Moss IR. Mu‐ and delta‐opioid receptor densities in respiratory‐related brainstem regions of neonatal swine. Brain Res Dev Brain Res 112: 1‐9, 1999.
 358. Lahiri S, Nishino T, Mokashi A, Mulligan E. Relative responses of aortic body and carotid body chemoreceptors to hypotension. JApplPhysiol 48 (5): 781‐788, 1980.
 359. Lalley PM. Mu‐opioid receptor agonist effects on medullary respiratory neurons in the cat: Evidence for involvement in certain types of ventilatory disturbances. Am J Physiol Regul Integr Comp Physiol 285: R1287‐R1304, 2003.
 360. Lalley PM. D1‐dopamine receptor blockade slows respiratory rhythm and enhances opioid‐mediated depression. Respir Physiol Neurobiol 145: 13‐22, 2005.
 361. Lalley PM. Opiate slowing of feline respiratory rhythm and effects on putative medullary phase‐regulating neurons. Am J Physiol Regul Integr Comp Physiol 290: R1387‐R1396, 2006.
 362. Lalley PM. Opioidergic and dopaminergic modulation of respiration. Respir Physiol Neurobiol 164: 160‐167, 2008.
 363. Lam AM, Clement JL, Knill RL. Surgical stimulation does not enhance ventilatory chemoreflexes during enflurane anaesthesia in man. Can Anaesth Soc J 27: 22‐28, 1980.
 364. Lang E, Kapila A, Shlugman D, Hoke JF, Sebel PS, Glass PS. Reduction of isoflurane minimal alveolar concentration by remifentanil. Anesthesiology 85: 721‐728, 1996.
 365. Larrabee MG, Posternak JM. Selective action of anesthetics on synapses and axons in mammalian sympathetic ganglia. J Neurophysiol 15: 91‐114, 1952.
 366. Laubie M, Drouillat M, Schmitt H. Discharge patterns of bulbar respiratory neurons in response to the morphinomimetic agent, fentanyl, in chloralosed dogs. Eur J Pharmacol 122: 301‐309, 1986.
 367. Launois S, Similowski T, Fleury B, Aubier M, Murciano D, Housset B, Pariente R, Derenne JP. The transition between apnoea and spontaneous ventilation in patients with coma due to voluntary intoxication with barbiturates and carbamates. Eur Respir J 3: 573‐578, 1990.
 368. Lawson EE, Waldrop TG, Eldridge FL. Naloxone enhances respiratory output in cats. J Appl Physiol 47: 1105‐1111, 1979.
 369. Lazarenko RM, Fortuna MG, Shi Y, Mulkey DK, Takakura AC, Moreira TS, Guyenet PG, Bayliss DA. Anesthetic activation of central respiratory chemoreceptor neurons involves inhibition of a THIK‐1‐like background K(+) current. J Neurosci 30: 9324‐9334, 2010.
 370. Lee C, Kwan WF, Tsai SK, Chen BJ, Cheng M. A clinical assessment of desflurane anaesthesia and comparison with isoflurane. Can J Anaesth 40: 487‐494, 1993.
 371. Lehmann KA, Mainka F. Ventilatory CO2‐response after alfentanil and sedative premedication (etomidate, diazepam and droperidol). A comparative study with human volunteers. Acta Anaesthesiol Belg 37: 3‐13, 1986.
 372. Leino K, Mildh L, Lertola K, Seppala T, Kirvela O. Time course of changes in breathing pattern in morphine‐ and oxycodone‐induced respiratory depression. Anaesthesia 54: 835‐840, 1999.
 373. Lerman J, Sikich N, Kleinman S, Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology 80: 814‐824, 1994.
 374. Li X, Czajkowski C, Pearce RA. Rapid and direct modulation of GABAA receptors by halothane. Anesthesiology 92: 1366‐1375, 2000.
 375. Liburn JK, Dundee JW, Moore J. Ketamine infusions. Anaesthesia 33: 315‐321, 1978.
 376. Lim TA, Inbasegaran K. Predicted effect compartment concentration of thiopental at loss of eyelash reflex. Br J Anaesth 86: 422‐424, 2001.
 377. Lin L‐H, Chen LL, Zirrolli JA, Harris RA. General anesthetics potentiate γ‐aminobutyric acid actions on γ‐aminobutyric acidA receptors expressed by xenopus oocytes: Lack of involvement of intracellular calcium. JPharmacolExpTher 263: 569‐578, 1992.
 378. Lindstedt L, Schaeffer PJ. Use of allometry in predicting anatomical and physiological parameters of mammals. Lab Anim 36: 1‐19, 2002.
 379. Lingamaneni R, Birch ML, Hemmings HC. Widespread inhibition of sodium channel‐dependent glutamate release from isolated nerve terminals by isoflurane and propofol. Anesthesiology 95: 1460‐1466, 2001.
 380. Lischke V, Behne M, Doelken P, Schledt U, Probst S, Vettermann J. Droperidol causes a dose‐dependent prolongation of the QT interval. Anesth Analg 79: 983‐986, 1994.
 381. Litman RS. Upper airway collapsibility: An emerging paradigm for measuring the safety of anesthetic and sedative agents. Anesthesiology 103: 453‐454, 2005.
 382. Litman RS, Hayes JL, Basco MG, Schwartz AR, Bailey PL, Ward DS. Use of dynamic negative airway pressure (DNAP) to assess sedative‐induced upper airway obstruction. Anesthesiology 96: 342‐345, 2002.
 383. Litman RS, McDonough JM, Marcus CL, Schwartz AR, Ward DS. Upper airway collapsibility in anesthetized children. Anesth Analg 102: 750‐754, 2006.
 384. Litman RS, Weissend EE, Shrier DA, Ward DS. Morphologic changes in the upper airway of children during awakening from propofol administration. Anesthesiology 96: 607‐611, 2002.
 385. Liu LM, Gaudreault P, Friedman PA, Goudsouzian NG, Liu PL. Methohexital plasma concentrations in children following rectal administration. Anesthesiology 62: 567‐570, 1985.
 386. Liu YY, Wong‐Riley MT, Liu JP, Jia Y, Liu HL, Jiao XY, Ju G. GABAergic and glycinergic synapses onto neurokinin‐1 receptor‐immunoreactive neurons in the pre‐Botzinger complex of rats: Light and electron microscopic studies. Eur J Neurosci 16: 1058‐1066, 2002.
 387. Lockhart SH, Rampil IJ, Yasuda N, Eger En, Weiskopf RB. Depression of ventilation by desflurane in humans. Anesthesiology 74: 484‐488, 1991.
 388. Lofland GK. The enhancement of hemodynamic performance in Fontan circulation using pain free spontaneous ventilation. Eur J Cardiothorac Surg 20: 114‐118, discussion 118‐119, 2001.
 389. Lonergan T, Goodchild AK, Christie MJ, Pilowsky PM. Mu opioid receptors in rat ventral medulla: Effects of endomorphin‐1 on phrenic nerve activity. Respir Physiol Neurobiol 138: 165‐178, 2003a.
 390. Lonergan T, Goodchild AK, Christie MJ, Pilowsky PM. Presynaptic delta opioid receptors differentially modulate rhythm and pattern generation in the ventral respiratory group of the rat. Neuroscience 121: 959‐973, 2003b.
 391. Lopez‐Barneo J, Ortega‐Saenz P, Pardal R, Pascual A, Piruat JI, Duran R, Gomez‐Diaz R. Oxygen sensing in the carotid body. Ann N Y Acad Sci 1177: 119‐131, 2009.
 392. Lopez‐Lopez JR, Perez‐Garcia MT. Oxygen sensitive Kv channels in the carotid body. Respir Physiol Neurobiol 157: 65‐74, 2007.
 393. Lotsch J. Pharmacokinetic‐pharmacodynamic modeling of opioids. J Pain Symptom Manage 29: S90‐S103, 2005.
 394. Lotsch J, Dudziak R, Freynhagen R, Marschner J, Geisslinger G. Fatal respiratory depression after multiple intravenous morphine injections. Clin Pharmacokinet 45: 1051‐1060, 2006.
 395. Lucas AN, Firth AM, Anderson GA, Vine JH, Edwards GA. Comparison of the effects of morphine administered by constant‐rate intravenous infusion or intermittent intramuscular injection in dogs. J Am Vet Med Assoc 218: 884‐891, 2001.
 396. Lumb AB. Anaesthesia. In: Lumb AB, editor. Nunn's Applied Respiratory Physiology (6th ed). Edinburgh, Philadelphia: Elsevier, Butterworth‐Heinemann, 2005, pp. 297‐326.
 397. Lydic R, Baghdoyan HA. Pedunculopontine stimulation alters respiration and increases ACh release in the pontine reticular formation. Am J Physiol 264: R544‐R554, 1993.
 398. Lydic R, Biebuyck JF. Sleep neurobiology: Relevance for mechanistic studies of anesthesia. BrJAnaesth 72: 506‐508, 1994.
 399. Lynn AM, Nespeca MK, Opheim KE, Slattery JT. Respiratory effects of intravenous morphine infusions in neonates, infants, and children after cardiac surgery. Anesth Analg 77: 695‐701, 1993.
 400. MacDonald JF, Bartlett MC, Mody I, Pahapill P, Reynolds JN, Salter MW, Schneiderman JH, Pennefather PS. Actions of ketamine, phencyclidine and MK‐801 on NMDA receptor currents in cultured mouse hippocampal neurones. J Physiol 432: 483‐508, 1991.
 401. MacIver MB. General anesthetic actions on transmission at glutamate and GABA synapses. In: Yaksh TL, editor. Anesthesia Biologic Foundations (1 ed). Philadelphia: Lippincott Raven Publishers, 1997, pp. 277‐286.
 402. MacIver MB, Mikulec AA, Amagasu SM, Monroe FA. Volatile anesthetics depress glutamate transmission via presynaptic actions. Anesthesiology 85: 823‐834, 1996.
 403. Mackenzie N, Grant IS. Comparison of propofol with methohexitone in the provision of anaesthesia for surgery under regional blockade. Br J Anaesth 57: 1167‐1172, 1985.
 404. Madison DV, Nicoll RA. Enkephalin hyperpolarizes interneurones in the rat hippocampus. J Physiol 398: 123‐130, 1988.
 405. Manchanda S, Leevers AM, Wilson CR, Simon PM, Skatrud JB, Dempsey JA. Frequency and volume thresholds for inhibition of inspiratory motor output during mechanical ventilation. Respir Physiol 105: 1‐16, 1996.
 406. Mankikian B, Cantineau JP, Sartene R, Clergue F, Viars P. Ventilatory pattern and chest wall mechanics during ketamine anesthesia in humans. Anesthesiology 65: 492‐499, 1986.
 407. Mansour A, Fox CA, Burke S, Akil H, Watson SJ. Immunohistochemical localization of the cloned mu opioid receptor in the rat CNS. J Chem Neuroanat 8: 283‐305, 1995.
 408. Mansour A, Watson SJ, Akil H. Opioid receptors: Past, present and future. Trends Neurosci 18: 69‐70, 1995.
 409. Manzke T, Guenther U, Ponimaskin EG, Haller M, Dutschmann M, Schwarzacher S, Richter DW. 5‐HT4(a) receptors avert opioid‐induced breathing depression without loss of analgesia. Science 301: 226‐229, 2003.
 410. Martin‐Schild S, Gerall AA, Kastin AJ, Zadina JE. Differential distribution of endomorphin 1‐ and endomorphin 2‐like immunoreactivities in the CNS of the rodent. J Comp Neurol 405: 450‐471, 1999.
 411. Marty J, Desmonts JM. Effects of fentanyl on respiratory pressure‐volume relationship in supine anesthetized children. Acta Anaesthesiol Scand 25: 293‐296, 1981.
 412. Mascia MP, Machu TK, Harris RA. Enhancement of homomeric glycine receptor function by long‐chain alcohols and anaesthetics. Br J Pharmacol 119: 1331‐1336, 1996.
 413. Mason KP, Zgleszewski SE, Dearden JL, Dumont RS, Pirich MA, Stark CD, D'Angelo P, Macpherson S, Fontaine PJ, Connor L, Zurakowski D. Dexmedetomidine for pediatric sedation for computed tomography imaging studies. Anesth Analg 103: 57‐62, 2006.
 414. Mason KP, Zurakowski D, Zgleszewski SE, Robson CD, Carrier M, Hickey PR, Dinardo JA. High dose dexmedetomidine as the sole sedative for pediatric MRI. Paediatr Anaesth 18: 403‐411, 2008.
 415. Masuda A, Haji A, Wakasugi M, Shibuya N, Shakunaga K, Ito Y. Differences in midazolam‐induced breathing patterns in healthy volunteers. Acta Anaesthesiol Scand 39: 785‐790, 1995.
 416. Masuda A, Ito Y, Haji A, Takeda R. The influence of halothane and thiopental on respiratory‐related nerve activities in decerebrate cats. Acta Anaesthesiol Scand 33: 660‐665, 1989.
 417. Mathru M, Esch O, Lang J, Herbert ME, Chaljub G, Goodacre B, vanSonnenberg E. Magnetic resonance imaging of the upper airway. Effects of propofol anesthesia and nasal continuous positive airway pressure in humans. Anesthesiology 84: 273‐279, 1996.
 418. Maze M, Angst MS. Dexmedetomidine and opioid interactions: Defining the role of dexmedetomidine for intensive care unit sedation. Anesthesiology 101: 1059‐1061, 2004.
 419. Mazoit JX. Pharmacokinetic/pharmacodynamic modeling of anesthetics in children: Therapeutic implications. Paediatr Drugs 8: 139‐150, 2006.
 420. Mazoit JX, Samii K. Binding of propofol to blood components: Implications for pharmacokinetics and for pharmacodynamics. Br J Clin Pharmacol 47: 35‐42, 1999.
 421. Mazzarelli MS, Haberer FP, Jaspar N, Miserocchi G. Mechanism of halothane‐induced tachypnea in cats. Anesthesiology 51: 522‐527, 1979.
 422. McCann ME, Bacsik J, Davidson A, Auble S, Sullivan L, Laussen P. The correlation of bispectral index with endtidal sevoflurane concentration and haemodynamic parameters in preschoolers. Paediatr Anaesth 12: 519‐525, 2002.
 423. McCormick CG. FDA Alert: Current FDA report on droperidol status and basis for ‘black box’ warning. ASA Newsletter 66(4): 19‐20, 2002.
 424. McCrimmon DR, Zuperku EJ, Hayashi F, Dogas Z, Hinrichsen CFL, Stuth EA, Tonkovic‐Capin M, Krolo M, Hopp FA. Modulation of the synaptic drive to respiratory premotor and motor neurons. Resp Physiol 110: 161‐176, 1997.
 425. McDougall SJ, Bailey TW, Mendelowitz D, Andresen MC. Propofol enhances both tonic and phasic inhibitory currents in second‐order neurons of the solitary tract nucleus (NTS). Neuropharmacology 54: 552‐563, 2008.
 426. McEwan AI, Smith C, Dyar O, Goodman D, Smith LR, Glass PS. Isoflurane minimum alveolar concentration reduction by fentanyl. Anesthesiology 78: 864‐869, 1993.
 427. McIntosh MP, Narita H, Kameyama Y, Rajewski RA, Goto H. Evaluation of mean arterial blood pressure, heart rate, and sympathetic nerve activity in rabbits after administration of two formulations of etomidate. Vet Anaesth Analg 34: 149‐156, 2007.
 428. McKeating K, Bali IM, Dundee JW. The effects of thiopentone and propofol on upper airway integrity. Anaesthesia 43: 638‐640, 1988.
 429. McMurphy RM, Hodgson DS. The minimum alveolar concentration of desflurane in cats. Vet Surg 24: 453‐455, 1995.
 430. Mealing GA, Lanthorn TH, Murray CL, Small DL, Morley P. Differences in degree of trapping of low‐affinity uncompetitive N‐methyl‐D‐aspartic acid receptor antagonists with similar kinetics of block. J Pharm Exp Therap 288: 204‐210, 1999.
 431. Meier S, Geiduschek J, Paganoni R, Fuehrmeyer F, Reber A. The effect of chin lift, jaw thrust, and continuous positive airway pressure on the size of the glottic opening and on stridor score in anesthetized, spontaneously breathing children. Anesth Analg 94: 494‐499, 2002.
 432. Mellen NM, Janczewski WA, Bocchiaro CM, Feldman JL. Opioid‐induced quantal slowing reveals dual networks for respiratory rhythm generation. Neuron 37: 821‐826, 2003.
 433. Mertens M. Pharmacokinetic and Pharmacodynamic Interactions between Intravenous Hypnotics and Opioids in Man. Leiden: Leiden University, 2002.
 434. Mertens MJ, Olofsen E, Engbers FH, Burm AG, Bovill JG, Vuyk J. Propofol reduces perioperative remifentanil requirements in a synergistic manner: Response surface modeling of perioperative remifentanil‐propofol interactions. Anesthesiology 99: 347‐359, 2003.
 435. Miao N, Frazer MJ, Lynch CIII. Volatile anesthetics depress Ca2+ transients and glutamate release in isolated cerebral synaptosomes. Anesthesiology 83: 593‐603, 1995.
 436. Michelsen LG, Salmenpera M, Hug CC Jr., Szlam F, VanderMeer D. Anesthetic potency of remifentanil in dogs. Anesthesiology 84: 865‐872, 1996.
 437. Mihic SJ, McQuilkin SJ, Eger EI 2nd, Ionescu P, Harris RA. Potentiation of gamma‐aminobutyric acid type A receptor‐mediated chloride currents by novel halogenated compounds correlates with their abilities to induce general anesthesia. Mol Pharmacol 46: 851‐857, 1994.
 438. Mikulec AA, Pittson S, Amagasu SM, Monroe FA, MacIver MB. Halothane depresses action potential conduction in hippocampal axons. Brain Research 796: 231‐238, 1998.
 439. Mildh L, Taittonen M, Leino K, Kirvela O. The effect of low‐dose ketamine on fentanyl‐induced respiratory depression. Anaesthesia 53: 965‐970, 1998.
 440. Mildh LH, Scheinin H, Kirvela OA. The concentration‐effect relationship of the respiratory depressant effects of alfentanil and fentanyl. Anesth Analg 93: 939‐946, 2001.
 441. Miller A, Sleigh JW, Barnard J, Steyn‐Ross DA. Does bispectral analysis of the electroencephalogram add anything but complexity?{dagger}. Br J Anaesth 92: 8‐13, 2004.
 442. Miller LG, Greenblatt DJ, Abernethy DR, Friedman H, Luu MD, Paul SM, Shader RI. Kinetics, brain uptake, and receptor binding characteristics of flurazepam and its metabolites. Psychopharmacology (Berl) 94: 386‐391, 1988.
 443. Ming Z, Griffith BL, Breese GR, Mueller RA, Criswell HE. Changes in the effect of isoflurane on N‐methyl‐D‐aspartic acid‐gated currents in cultured cerebral cortical neurons with time in culture: Evidence for subunit specificity. Anesthesiology 97: 856‐867, 2002.
 444. Ming Z, Knapp DJ, Mueller RA, Breese GR, Criswell HE. Differential modulation of GABA‐ and NMDA‐gated currents by ethanol and isoflurane in cultured rat cerebral cortical neurons. Brain Res 920: 117‐124, 2001.
 445. Minto CF, Schnider TW, Short TG, Gregg KM, Gentilini A, Shafer SL. Response surface model for anesthetic drug interactions. Anesthesiology 92: 1603‐1616, 2000.
 446. Mitsis GD, Governo RJ, Rogers R, Pattinson KT. The effect of remifentanil on respiratory variability, evaluated with dynamic modeling. J Appl Physiol 106: 1038‐1049, 2009.
 447. Mohan RM, Amara CE, Cunningham DA, Duffin J. Measuring central‐chemoreflex sensitivity in man: Rebreathing and steady‐state methods compared. Respir Physiol 115: 23‐33, 1999.
 448. Mohler H. GABA(A) receptor diversity and pharmacology. Cell Tissue Res 326: 505‐516, 2006.
 449. Molliex S, Dureuil B, Montravers P, Desmonts JM. Effects of midazolam on respiratory muscles in humans. Anesth Analg 77: 592‐597, 1993.
 450. Monitoring ASoATFoIAaBF. Practice Advisory for Intraoperative Awareness and Brain Function Monitoring, A Report by the American Society of Anesthesiologists Task Force on Intraoperative Awareness. Anesthesiology 2006; 104: 847‐64.
 451. Monk TG, Saini V, Weldon BC, Sigl JC. Anesthetic management and one‐year mortality after noncardiac surgery. Anesth Analg 100: 4‐10, 2005.
 452. Montandon G, Qin W, Liu H, Ren J, Greer JJ, Horner RL. PreBotzinger complex neurokinin‐1 receptor‐expressing neurons mediate opioid‐induced respiratory depression. J Neurosci 31: 1292‐1301.
 453. Montravers P, Dureuil B, Desmonts JM. Effects of i.v. midazolam on upper airway resistance. Br J Anaesth 68: 27‐31, 1992.
 454. Montravers P, Dureuil B, Molliex S, Desmonts JM. Effects of intravenous midazolam on the work of breathing. Anesth Analg 79: 558‐562, 1994.
 455. Moore LR, Bikhazi GB, Tuttle RR, Weidler DJ. Antagonism of fentanyl‐induced respiratory depression with nalmefene. Methods Find Exp Clin Pharmacol 12: 29‐35, 1990.
 456. Moote CA, Knill RL, Clement J. Ventilatory compensation for continous inspiratory resistive and elastic loads during halothane anesthesia in humans. Anesthesiology 64: 582‐589, 1986.
 457. Mora CT, Torjman M, White PF. Sedative and ventilatory effects of midazolam infusion: Effect of flumazenil reversal. Can J Anaesth 42: 677‐684, 1995.
 458. Morel DR, Forster A, Gemperle M. Noninvasive evaluation of breathing pattern and thoraco‐abdominal motion following the infusion of ketamine or droperidol in humans. Anesthesiology 65: 392‐398, 1986.
 459. Morgado‐Valle C, Feldman JL. NMDA receptors in preBotzinger complex neurons can drive respiratory rhythm independent of AMPA receptors. J Physiol 582: 359‐368, 2007.
 460. Morin‐Surun MP, Gacel G, Champagnat J, Denavit‐Saubie M, Roques BP. Pharmacological identification of delta and mu opiate receptors on bulbar respiratory neurons. Eur J Pharmacol 98: 241‐247, 1984.
 461. Morray JP, Geiduschek JM, Ramamoorthy C, Haberkern CM, Hackel A, Caplan RA, Domino KB, Posner K, Cheney FW. Anesthesia‐related cardiac arrest in children: Initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) Registry. Anesthesiology 93: 6‐14, 2000.
 462. Morray JP, Nobel R, Bennet L, Hanson MA. The effect of halothane on phrenic and chemoreceptor responses to hypoxia in anesthetized kittens. Anesth Analg 83: 329‐335, 1996.
 463. Morrell MJ, Browne HA, Adams L. The respiratory response to inspiratory resistive loading during rapid eye movement sleep in humans. J Physiol 526 (Pt 1): 195‐202, 2000.
 464. Mortero RF, Clark LD, Tolan MM, Metz RJ, Tsueda K, Sheppard RA. The effects of small‐dose ketamine on propofol sedation: Respiration, postoperative mood, perception, cognition, and pain. Anesth Analg 92: 1465‐1469, 2001.
 465. Moskowitz AS, Goodman RR. Autoradiographic distribution of mu1 and mu2 opioid binding in the mouse central nervous system. Brain Res 360: 117‐129, 1985.
 466. Moss IR, Laferriere A. Central neuropeptide systems and respiratory control during development. Respir Physiol Neurobiol 131: 15‐27, 2002.
 467. Muir WW 3rd, Gadawski JE. Respiratory depression and apnea induced by propofol in dogs. Am J Vet Res 59: 157‐161, 1998.
 468. Mulkey DK, Henderson RA 3rd, Ritucci NA, Putnam RW, Dean JB. Oxidative stress decreases pHi and Na(+)/H(+) exchange and increases excitability of solitary complex neurons from rat brain slices. Am J Physiol Cell Physiol 286: C940‐C951, 2004.
 469. Mulkey DK, Stornetta RL, Weston MC, Simmons JR, Parker A, Bayliss DA, Guyenet PG. Respiratory control by ventral surface chemoreceptor neurons in rats. Nat Neurosci 7: 1360‐1369, 2004.
 470. Mulroy MF 2nd, Coombs JH, Isenberg MD, Fairley HB. Age, chronic obstructive pulmonary disease, and Innovar induced ventilatory depression during regional anesthesia. Anesth Analg 56: 826‐830, 1977.
 471. Munson ES, Larson CP, Bobad AA, Regan MJ, Buechel DR, Eger EI, II. The effects of halothane, flurane and cyclopropane on ventilation: A comparative study in man. Anesthesiology 27: 716‐728, 1966.
 472. Murakoshi T, Suzue T, Tamai S. A pharmacological study on respiratory rhythm in the isolated brainstem‐spinal cord preparation of the newborn rat. Br J Pharmacol 86: 95‐104, 1985.
 473. Murray DJ, Mehta MP, Forbes RB. The additive contribution of nitrous oxide to isoflurane MAC in infants and children. Anesthesiology 75: 186‐190, 1991.
 474. Murray DJ, Mehta MP, Forbes RB, Dull DL. Additive contribution of nitrous oxide to halothane MAC in infants and children. Anesth Analg 71: 120‐124, 1990.
 475. Mustapic S, Radocaj T, Sanchez A, Dogas Z, Stucke AG, Hopp FA, Stuth EA, Zuperku EJ. Clinically relevant infusion rates of mu‐opioid agonist remifentanil cause bradypnea in decerebrate dogs but not via direct effects in the pre‐Botzinger complex region. J Neurophysiol 103: 409‐418, 2010.
 476. Mustapic S RT, Stucke AG, Dogas Z, Stuth EA, Zuperku EJ. Local microejection of mu‐opioids into the pre‐Bötzinger complex (pBC) region produces opposite effects on breathing rate to systemic mu‐opioid infusion in decerebrate dogs. FASEB J 23: 960‐966, 2009.
 477. Mustola ST, Rorarius MG, Baer GA, Rosenberg P, Seppala T, Harmoinen A. Potency of propofol, thiopentone and ketamine at various endpoints in New Zealand White rabbits. Lab Anim 34: 36‐45, 2000.
 478. Mutolo D, Bongianni F, Cinelli E, Pantaleo T. Role of excitatory amino acids in the mediation of tracheobronchial cough induced by citric acid inhalation in the rabbit. Brain Res Bull 80: 22‐29, 2009.
 479. Mutolo D, Bongianni F, Nardone F, Pantaleo T. Respiratory responses evoked by blockades of ionotropic glutamate receptors within the Botzinger complex and the pre‐Botzinger complex of the rabbit. Eur J Neurosci 21: 122‐134, 2005.
 480. Nagyova B, Dorrington KL, Gill EW, Robbins PA. Comparison of the effects of sub‐hypnotic concentrations of propofol and halothane on the acute ventilatory response to hypoxia. Br J Anaesth 75: 713‐718, 1995.
 481. Nagyova B, Dorrington KL, Robbins PA. Effect of low‐dose enflurane on the ventilatory response to hypoxia in humans. Br J Anaesth 72: 509‐514, 1994.
 482. Nakamura S, Hayashi K, Sakamaki H, Murakami Y, Tsuchiya M, Mishima M, Nishida M, Takahara T, Hitosugi N, Hatsukari I, Mizukami S, Nagasaka H, Miyata Y. Propofol depresses the activity of hypoglossal nerve more than that of phrenic nerve in rabbits. Masui 52: 135‐142, 2003.
 483. Nakata Y, Goto T, Ishiguro Y, Terui K, Kawakami H, Santo M, Niimi Y, Morita S. Minimum alveolar concentration (MAC) of xenon with sevoflurane in humans. Anesthesiology 94: 611‐614, 2001.
 484. Nandi PR, Charlesworth CH, Taylor SJ, Nunn JF, Dore CJ. Effect of general anaesthesia on the pharynx. Br J Anaesth 66: 157‐162, 1991.
 485. Narang S, Harte BH, Body SC. Anesthesia for patients with a mediastinal mass. Anesthesiol Clin North America 19: 559‐579, 2001.
 486. Negre I, Gueneron JP, Ecoffey C, Penon C, Gross JB, Levron JC, Samii K. Ventilatory response to carbon dioxide after intramuscular and epidural fentanyl. Anesth Analg 66: 707‐710, 1987.
 487. Neidhart P, Burgener MC, Schwieger I, Suter PM. Chest wall rigidity during fentanyl‐ and midazolam‐fentanyl induction: Ventilatory and haemodynamic effects. Acta Anaesthesiol Scand 33: 1‐5, 1989.
 488. Neubauer JA, Melton JE, Edelman NH. Modulation of respiration during brain hypoxia. J Appl Physiol 68: 441‐451, 1990.
 489. Nielsen AM, Bisgard GE, Vidruk EH. Carotid chemoreceptor activity during acute and sustained hypoxia in goats. J Appl Physiol 65 (4): 1796‐1802, 1988.
 490. Nieuwenhuijs D. Cardiorespiratory Control in the Perioperative Patient: From Bench to Bedside. Leiden: Leiden University, 2002.
 491. Nieuwenhuijs D, Sarton E, Teppema L, Dahan A. Propofol for monitored anesthesia care: Implications on hypoxic control of cardiorespiratory responses. Anesthesiology 92: 46‐54, 2000.
 492. Nieuwenhuijs D, Sarton E, Teppema LJ, Kruyt E, Olievier I, vanKleef J, Dahan A. Respiratory sites of action of propofol. Anesthesiology 95: 889‐895, 2001.
 493. Nieuwenhuijs DJ, Olofsen E, Romberg RR, Sarton E, Ward D, Engbers F, Vuyk J, Mooren R, Teppema LJ, Dahan A. Response surface modeling of remifentanil‐propofol interaction on cardiorespiratory control and bispectral index. Anesthesiology 98: 312‐322, 2003.
 494. Nishikawa K, MacIver MB. Excitatory synaptic transmission mediated by NMDA receptors is more sensitive to isoflurane than are non‐NMDA receptor‐mediated responses. Anesthesiology 92: 228‐236, 2000.
 495. Nishikawa K, MacIver MB. Agent‐selective effects of volatile anesthetics on GABAA receptor‐mediated synaptic inhibition in hippocampal interneurons. Anesthesiology 94: 340‐347, 2001.
 496. Nishikawa K, Maclver MB. Membrane and synaptic actions of halothane on rat hippocampal pyramidal neurons and inhibitory interneurons. J Neurosci 20: 5915‐5923, 2000.
 497. Nishino T, Isono S, Ide T. A low concentration of nitrous oxide reduces dyspnoea produced by a combination of hypercapnia and severe elastic load. Br J Anaesth 82: 14‐19, 1999.
 498. Nishino T, Kochi T. Effects of surgical stimulation on the apnoeic tresholds for carbon dioxide during anaesthesia with sevoflurane. Brit J Anaesth 73: 583‐586, 1994.
 499. Nishino T, Kohchi T, Yonezawa T, Honda Y. Responses of recurrent laryngeal, hypoglossal, and phrenic nerves to increasing depths of anesthesia with halothane or enflurane in vagotomized cats. Anesthesiology 63: 404‐409, 1985.
 500. Nishino T, Shirahata M, Yonezawa T, Honda Y. Comparison of changes in the hypoglossal and the phrenic nerve activity in response to increasing depth of anesthesia in cats. Anesthesiology 60: 19‐24, 1984.
 501. Nunn JF, Ezi‐Ashi TI. The respiratory effects of resistance to breathing in anesthetized man. Anesthesiology 22: 174‐185, 1961.
 502. O'Brien JA, Berger AJ. Cotransmission of GABA and glycine to brain stem motoneurons. J Neurophysiol 82: 1638‐1641, 1999.
 503. O'Brien JA, Isaacson JS, Berger AJ. NMDA and non‐NMDA receptors are co‐localized at excitatory synapses of rat hypoglossal motoneurons. Neurosci Lett 227: 5‐8, 1997.
 504. Oberer C, von Ungern‐Sternberg BS, Frei FJ, Erb TO. Respiratory reflex responses of the larynx differ between sevoflurane and propofol in pediatric patients. Anesthesiology 103: 1142‐1148, 2005.
 505. Ochiai R, Guthrie RD, Motoyama EK. Effects of varying concentrations of halothane on the activity of the genioglossus, intercostals, and the diaphragm in cats: An electromyographic study. Anesthesiology 70: 812‐816, 1989.
 506. Ochiai R, Guthrie RD, Motoyama EK. Differential sensitivity to halothane anesthesia of the genioglossus, intercostals, and diaphragm in kittens. Anesth Analg 74: 338‐344, 1992.
 507. Okada Y, Kawai A, Muckenhoff K, Scheid P. Role of the pons in hypoxic respiratory depression in the neonatal rat. Respir Physiol 111: 55‐63, 1998.
 508. Okawa K, Ichinohe T, Kaneko Y. A Comparison of propofol and dexmedetomidine for intravenous sedation: A randomized, cCrossover study of the effects on the central and autonomic nervous systems. Anesth Analg, 2009.
 509. Onimaru H, Arata A, Homma I. Neuronal mechanisms of respiratory rhythm generation: An approach using in vitro preparation. Jpn J Physiol 47: 385‐403, 1997.
 510. Onimaru H, Homma I. A novel functional neuron group for respiratory rhythm generation in the ventral medulla. J Neurosci 23: 1478‐1486, 2003.
 511. Onimaru H, Homma I. Point:Counterpoint: The parafacial respiratory group (pFRG)/pre‐Botzinger complex (preBotC) is the primary site of respiratory rhythm generation in the mammal. Point: The PFRG is the primary site of respiratory rhythm generation in the mammal. J Appl Physiol 100: 2094‐2095, 2006.
 512. Onimaru H, Homma I. Two modes of respiratory rhythm generation in the newborn rat brainstem‐spinal cord preparation. Adv Exp Med Biol 605: 104‐108, 2008.
 513. Onimaru H, Kumagawa Y, Homma I. Respiration‐related rhythmic activity in the rostral medulla of newborn rats. J Neurophysiol 96: 55‐61, 2006.
 514. Orem J, Netick A. Behavioral control of breathing in the cat. Brain Res 366: 238‐253, 1986.
 515. Orem J, Trotter RH. Behavioral control of breathing. NIPS 9: 228‐232, 1994.
 516. Orser BA, Bertlik M, Wang LY, MacDonald JF. Inhibition by propofol (2,6 di‐isopropylphenol) of the N‐methyl‐D‐aspartate subtype of glutamate receptor in cultured hippocampal neurones. Brit J Pharmacol 116: 1761‐1768, 1995.
 517. Orser BA, Pennefather PS, MacDonald JF. Multiple Mechanisms of ketamine blockade of N‐methyl‐D‐aspartate receptors. Anesthesiology 86: 903‐917, 1997.
 518. Otsuka H. Effects of volatile anesthetics on respiratory activity and chemosensitivity in the isolated brainstem‐spinal cord of the newborn rat. Hokkaido Igaku Zasshi 73: 117‐136, 1998.
 519. Ouyang W, Hemmings HC Jr. Depression by isoflurane of the action potential and underlying voltage‐gated ion currents in isolated rat neurohypophysial nerve terminals. J Pharmacol Exp Ther 312: 801‐808, 2005.
 520. Ouyang W, Herold KF, Hemmings HC Jr. Comparative effects of halogenated inhaled anesthetics on voltage‐gated Na+ channel function. Anesthesiology 110: 582‐590, 2009.
 521. Ouyang W, Wang G, Hemmings HC Jr. Isoflurane and propofol inhibit voltage‐gated sodium channels in isolated rat neurohypophysial nerve terminals. Mol Pharmacol 64: 373‐381, 2003.
 522. Pandit JJ. The variable effect of low‐dose volatile anaesthetics on the acute ventilatory response to hypoxia in humans: A quantitative review. Anaesthesia 57: 632‐643, 2002.
 523. Pandit JJ. Effect of low dose inhaled anaesthetic agents on the ventilatory response to carbon dioxide in humans: A quantitative review. Anaesthesia 60: 461‐469, 2005.
 524. Pandit JJ, O'Gallagher K. Effects of volatile anesthetics on carotid body response to hypoxia in animals. Adv Exp Med Biol 605: 46‐50, 2008.
 525. Paris A, Philipp M, Tonner PH, Steinfath M, Lohse M, Scholz J, Hein L. Activation of alpha 2B‐adrenoceptors mediates the cardiovascular effects of etomidate. Anesthesiology 99: 889‐895, 2003.
 526. Paskin S, Skovsted P, Smith TC. Failure of the Hering‐Breuer reflex to account for tachypnea in anesthetized man. Anesthesiology 29: 550‐558, 1968.
 527. Pasternak GW. Multiple opiate receptors: Deja vu all over again. Neuropharmacology 47 (Suppl 1): 312‐323, 2004.
 528. Pasternak GW, Wood PJ. Multiple mu opiate receptors. Life Sci 38: 1889‐1898, 1986.
 529. Patel AJ, Honoré E. Anesthetic‐sensitive 2P domanin K+ channels. Anesthesiology 95: 1013‐1021, 2001.
 530. Patel AJ, Honore E, Lesage F, Fink M, Romey G, Lazdunski M. Inhalational anesthetics activate two‐pore‐domain background K channels. Nat Neurosci 2: 422‐426, 1999.
 531. Patil SP, Schneider H, Marx JJ, Gladmon E, Schwartz AR, Smith PL. Neuromechanical control of upper airway patency during sleep. J Appl Physiol 102: 547‐556, 2007.
 532. Pattinson KT. Opioids and the control of respiration. Br J Anaesth 100: 747‐758, 2008.
 533. Pattinson KT, Governo RJ, MacIntosh BJ, Russell EC, Corfield DR, Tracey I, Wise RG. Opioids depress cortical centers responsible for the volitional control of respiration. J Neurosci 29: 8177‐8186, 2009.
 534. Pavlin EG, Hornbein TF. Anesthesia and the control of ventilation. In: Fishman P, editor. Handbook of Physiology: The Respiratory System. Bethesda, MD: American Physiological Society, 1986, pp. 793‐813.
 535. Peat SJ, Hanna MH, Woodham M, Knibb AA, Ponte J. Morphine‐6‐glucuronide: Effects on ventilation in normal volunteers. Pain 45: 101‐104, 1991.
 536. Penny DJ, Redington AN. Doppler echocardiographic evaluation of pulmonary blood flow after the Fontan operation: The role of the lungs. Br Heart J 66: 372‐374, 1991.
 537. Peoples RW, Weight FF. Anesthetic actions on excitatory amino acid receptors. In: Yaksh TL, Lynch III C, Zapol WM, Maze M, Biebuyck JF, Saidman LJ, editors. Anesthesia Biologic Foundations (1st ed). Philadelphia: Lippincott‐Raven Publishers, 1997, pp. 239‐258.
 538. Perouansky M, Baranov D, Salman M, Yaari Y. Effects of halothane on glutamate receptor‐mediated excitatory postsynaptic currents. Anesthesiology 83: 109‐119, 1995.
 539. Perouansky M, Kirson ED, Yaari Y. Halothane blocks synaptic excitation of inhibitory interneurons. Anesthesiology 85: 1431‐1438, 1996.
 540. Peters JH, McDougall SJ, Mendelowitz D, Koop DR, Andresen MC. Isoflurane differentially modulates inhibitory and excitatory synaptic transmission to the solitary tract nucleus. Anesthesiology 108: 675‐683, 2008.
 541. Piat V, Dubois MC, Johanet S, Murat I. Induction and recovery characteristics and hemodynamic responses to sevoflurane and halothane in children. Anesth Analg 79: 840‐844, 1994.
 542. Pierce TL, Wessendorf MW. Immunocytochemical mapping of endomorphin‐2‐immunoreactivity in rat brain. J Chem Neuroanat 18: 181‐207, 2000.
 543. Pierrefiche O, Foutz AS, Champagnat J, Denavit‐Saubie M. NMDA and non‐NMDA receptors may play distinct roles in timing mechanisms and transmission in the feline respiratory network. JPhysiol 474 (3): 509‐523, 1994.
 544. Pierrefiche O, Foutz AS, Denavit‐Saubie M. Pneumotaxic mechanisms in the non‐human primate: Effect of the N‐methyl‐D‐aspartate (NMDA) antagonist ketamine. Neurosci Lett 119: 90‐93, 1990.
 545. Pistis M, Belelli D, Peters JA, Lambert JJ. The interaction of general anaesthetics with recombinant GABAA and glycine receptors expressed in Xenopus laevis oocytes: A comparative study. Br J Pharmacol 122: 1707‐1719, 1997.
 546. Pokorski M, Sieradzan B, Karczewski W. Apneustic respiration of ketamine is not antagonized in the cat. Jpn J Physiol 37: 735‐740, 1987.
 547. Ponte J, Sadler CL. Effect of halothane, enflurane and isoflurane on carotid body chemoreceptor activity in the rabbit and the cat. Br J Anaesth 62: 33‐40, 1989a.
 548. Ponte J, Sadler CL. Effect of thiopentone, etomidate and propofol on carotid body chemoreceptor activity in the rabbit and the cat. Br J Anaesth 62: 41‐45, 1989b.
 549. Powell FL, Milsom WK, Mitchell GS. Time domains of the hypoxic ventilatory response. Respir Physiol 112: 123‐134, 1998.
 550. Powers KS, Nazarian EB, Tapyrik SA, Kohli SM, Yin H, van der Jagt EW, Sullivan JS, Rubenstein JS. Bispectral index as a guide for titration of propofol during procedural sedation among children. Pediatrics 115: 1666‐1674, 2005.
 551. Prabhakar NR. Oxygen sensing by the carotid body chemoreceptors. J Appl Physiol 88: 2287‐2295, 2000.
 552. Pratap JN, Harding L. Critical overfilling of a vaporizer. Eur J Anaesthesiol 26: 90‐91, 2009.
 553. Preckel B, Schlack W, Comfere T, Obal D, Barthel H, Thamer V. Effects of enflurane, isoflurane, sevoflurane and desflurane on reperfusion injury after regional myocardial ischaemia in the rabbit heart in vivo. Br J Anaesth 81: 905‐912, 1998.
 554. Priano LL, Bernards C, Marrone B. Effect of anesthetic induction agents on cardiovascular neuroregulation in dogs. Anesth Analg 68: 344‐349, 1989.
 555.European Agency for the Evaluation of Medicinal products. Committee for Veterinary Medicinal Products. Thiopental Sodium. Summary Report, 1999.
 556. Prokocimer P, Delavault E, Rey F, Lefevre P, Mazze RI, Desmonts JM. Effects of droperidol on respiratory drive in humans. Anesthesiology 59: 113‐116, 1983.
 557. Qian N, Sejnowski TJ. When is an inhibitory synapse effective? Proc Natl Acad Sci U S A 87: 8145‐8149, 1990.
 558. Radulovacki M, Pavlovic S, Saponjic J, Carley DW. Intertrigeminal region attenuates reflex apnea and stabilizes respiratory pattern in rats. Brain Res 975: 66‐72, 2003.
 559. Raeder J. Ketamine, revival of a versatile intravenous anaesthetic. Adv Exp Med Biol 523: 269‐277, 2003.
 560. Raeder JC, Stenseth LB. Ketamine: A new look at an old drug. Curr Opin Anaesthesiol 13: 463‐468, 2000.
 561. Rampil IJ, King BS. Volatile anesthetics depress spinal motor neurons. Anesthesiology 85: 129‐134, 1996.
 562. Rampil IJ, Mason P, Singh H. Anesthetic potency (MAC) is independent of forebrain structures in the rat. Anesthesiology 78: 707‐712, 1993.
 563. Ratnakumari L, Hemmings HC. Effects of propofol on sodium channel‐dependent sodium influx and glutamate release in rat cerebrocortical synaptosomes. Anesthesiology 86: 428‐439, 1997.
 564. Ratnakumari L, Hemmings HC. Inhibition of presynaptic sodium channels by halothane. Anesthesiology 88: 1043‐1054, 1998.
 565. Rau V, Oh I, Laster M, Eger EI 2nd, Fanselow MS. Isoflurane suppresses stress‐enhanced fear learning in a rodent model of post‐traumatic stress disorder. Anesthesiology 110: 487‐495, 2009.
 566. Read DJ, Freedman S, Kafer ER. Pressures developed by loaded inspiratory muscles in conscious and anesthetized man. J Appl Physiol 37: 207‐218, 1974.
 567. Reber A, Wetzel SG, Schnabel K, Bongartz G, Frei FJ. Effect of combined mouth closure and chin lift on upper airway dimensions during routine magnetic resonance imaging in pediatric patients sedated with propofol. Anesthesiology 90: 1617‐1623, 1999.
 568. Rehberg B, Xiao Y‐H, Duch DS. Central nervous system sodium channels are significantly depressed at clinical concentrations of volatile anesthetics. Anesthesiology 84: 1223‐1233, 1996.
 569. Rekling JC, Feldman JL. PreBötzinger complex and pacemaker neurons: Hypothesized site and kernel for respiratory rhythm generation. Annu Rev Physiol 60: 385‐404, 1998.
 570. Reyes EP, Fernandez R, Larrain C, Zapata P. Carotid body chemosensory activity and ventilatory chemoreflexes in cats persist after combined cholinergic‐purinergic block. Respir Physiol Neurobiol 156: 23‐32, 2007.
 571. Richards CD. The synaptic basis of general anaesthesia. Eur J Anaesthesiol 12: 5‐19, 1995.
 572. Richards CD. Anaesthetic modulation of synaptic transmission in the mammalian CNS. Br J Anaesth 89: 79‐90, 2002.
 573. Rigg JR, Goldsmith CH. Recovery of ventilatory response to carbon dioxide after thiopentone, morphine and fentanyl in man. Can Anaesth Soc J 23: 370‐382, 1976.
 574. Robertson SA, Taylor PM, Sear JW, Keuhnel G. Relationship between plasma concentrations and analgesia after intravenous fentanyl and disposition after other routes of administration in cats. J Vet Pharmacol Ther 28: 87‐93, 2005.
 575. Roda F, Pio J, Bianchi AL, Gestreau C. Effects of anesthetics on hypoglossal nerve discharge and c‐Fos expression in brainstem hypoglossal premotor neurons. J Comp Neurol 468: 571‐586, 2004.
 576. Roerig DL, Kotrly KJ, Vucins EJ, Ahlf SB, Dawson CA, Kampine JP. First pass uptake of fentanyl, meperidine, and morphine in the human lung. Anesthesiology 67: 466‐472, 1987.
 577. Roizen MF, Horrigan RW, Frazer BM. Anesthetic doses blocking adrenergic (stress) and cardiovascular responses to incision–MAC BAR. Anesthesiology 54: 390‐398, 1981.
 578. Roland EJ, Wierda JM, Eurin BG, Roupie E. Pharmacodynamic behaviour of vecuronium in primary hyperparathyroidism. Can J Anaesth 41: 694‐698, 1994.
 579. Romberg R, Olofsen E, Sarton E, Teppema L, Dahan A. Pharmacodynamic effect of morphine‐6‐glucuronide versus morphine on hypoxic and hypercapnic breathing in healthy volunteers. Anesthesiology 99: 788‐798, 2003.
 580. Romberg R, Sarton E, Teppema L, Matthes HW, Kieffer BL, Dahan A. Comparison of morphine‐6‐glucuronide and morphine on respiratory depressant and antinociceptive responses in wild type and mu‐opioid receptor deficient mice. Br J Anaesth 91: 862‐870, 2003.
 581. Rondouin G, Boudinot E, Champagnat J, Denavit‐Saubie M. Effects of sulfonated Leu‐enkephalin applied iontophoretically to cat respiratory neurones. Neuropharmacology 20: 963‐967, 1981.
 582. Rothman RB, Xu H, Wang JB, Partilla JS, Kayakiri H, Rice KC, Uhl GR. Ligand selectivity of cloned human and rat opioid mu receptors. Synapse 21: 60‐64, 1995.
 583. Rothstein RJ, Narce SL, deBerry‐Borowiecki B, Blanks RH. Respiratory‐related activity of upper airway muscles in anesthetized rabbit. J Appl Physiol 55: 1830‐1836, 1983.
 584. Rowley TJ, Daniel D, Flood P. The role of adrenergic and cholinergic transmission in volatile anesthetic‐induced pain enhancement. Anesth Analg 100: 991‐995, 2005.
 585. Rudolph U, Antkowiak B. Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci 5: 709‐720, 2004.
 586. Ruiz F, Dierssen M, Florez J, Hurle MA. Potentiation of acute opioid‐induced respiratory depression and reversal of tolerance by the calcium antagonist nimodipine in awake rats. Naunyn Schmiedebergs Arch Pharmacol 348: 633‐637, 1993.
 587. Russell GB, Graybeal JM. Direct measurement of nitrous oxide MAC and neurologic monitoring in rats during anesthesia under hyperbaric conditions. Anesth Analg 75: 995‐999, 1992.
 588. Rutherford JS, Logan MR, Drummond GB. Changes in end‐expiratory lung volume on induction of anaesthesia with thiopentone or propofol. Br J Anaesth 73: 579‐582, 1994.
 589. Rutherfurd SD, Gundlach AL. Opioid peptide gene expression in the nucleus tractus solitarius of rat brain and increases induced by unilateral cervical vagotomy: Implications for role of opioid neurons in respiratory control mechanisms. Neuroscience 57: 797‐810, 1993.
 590. Rybak IA, Moxon KA, Giszter S, Chapin JK. Computational modeling of integration of voluntary/behavioral and automatic mechanisms for breathing control. Adv Exp Med Biol 499: 425‐430, 2001.
 591. Rybak IA, Shevtsova NA, Paton JF, Dick TE, St‐John WM, Morschel M, Dutschmann M. Modeling the ponto‐medullary respiratory network. Respir Physiol Neurobiol 143: 307‐319, 2004.
 592. Rybak IA, Shevtsova NA, St‐John WM, Paton JF, Pierrefiche O. Endogenous rhythm generation in the pre‐Botzinger complex and ionic currents: Modelling and in vitro studies. Eur J Neurosci 18: 239‐257, 2003.
 593. Saetta M, Mortola JP. Breathing pattern and CO2 response in newborn rats before and during anesthesia. J Appl Physiol 58: 1988‐1996, 1985.
 594. Sales N, Riche D, Roques BP, Denavit‐Saubie M. Localization of mu‐ and delta‐opioid receptors in cat respiratory areas: An autoradiographic study. Brain Res 344: 382‐386, 1985.
 595. Sanchez A, Mustapic S, Zuperku EJ, Stucke AG, Hopp FA, Stuth EAE. Role of inhibitory neurotransmission in the control of canine hypoglossal motoneuron activity in vivo. J Neurophysiol 101: 1211‐1221, 2009.
 596. Sanders JC, King MA, Mitchell RB, Kelly JP. Perioperative complications of adenotonsillectomy in children with obstructive sleep apnea syndrome. Anesth Analg 103: 1115‐1121, 2006.
 597. Santiago TV, Edelman NH. Opioids and breathing. J Appl Physiol 59: 1675‐1685, 1985.
 598. Santiago TV, Goldblatt K, Winters K, Pugliese AC, Edelman NH. Respiratory consequences of methadone: The response to added resistance to breathing. Am Rev Respir Dis 122: 623‐628, 1980.
 599. Santiago TV, Remolina C, Scoles V 3rd, Edelman NH. Endorphins and the control of breathing. Ability of naloxone to restore flow‐resistive load compensation in chronic obstructive pulmonary disease. N Engl J Med 304: 1190‐1195, 1981.
 600. Saponjic J, Radulovacki M, Carley DW. Respiratory pattern modulation by the pedunculopontine tegmental nucleus. Respir Physiol Neurobiol 138: 223‐237, 2003.
 601. Sarkar M, Laussen PC, Zurakowski D, Shukla A, Kussman B, Odegard KC. Hemodynamic responses to etomidate on induction of anesthesia in pediatric patients. Anesth Analg 101: 645‐650, 2005.
 602. Sarner JB, Levine M, Davis PJ, Lerman J, Cook DR, Motoyama EK. Clinical characteristics of sevoflurane in children. Anesthesiology 82: 38‐46, 1995.
 603. Sarton E, Dahan A, Teppema L, Berkenbosch A, van den Elsen M, van Kleef J. Influence of acute pain induced by activation of cutaneous nociceptors on ventilatory control. Anesthesiology 87: 289‐296, 1997.
 604. Sarton E, Dahan A, Teppema L, van den Elsen M, Olofsen E, Berkenbosch A, van Kleef J. Acute pain and central nervous system arousal do not restore impaired hypoxic ventilatory response during sevoflurane sedation. Anesthesiology 85: 295‐303, 1996.
 605. Sarton E, Romberg R, Nieuwenhuijs D, Teppema LJ, Vuyk J, Schraag S, Dahan A. The effect of anesthetics on control of respiration. Anaesthesist 51: 285‐291, 2002.
 606. Sarton E, Teppema L, Dahan A. Sex differences in morphine‐induced ventilatory depression reside within the peripheral chemoreflex loop. Anesthesiology 90: 1329‐1338, 1999.
 607. Sarton E, Teppema LJ, Olievier C, Nieuwenhuijs D, Matthes HWD, Kieffer BL, Dahan A. The involvement of the μ‐opioid receptor in ketamine‐induced respiratory depression and antinociception. Anesth Analg 93: 1495‐1500, 2001.
 608. Sarton E, van der Wal M, Nieuwenhuijs D, Teppema L, Robotham JL, Dahan A. Sevoflurane‐induced reduction of hypoxic drive is sex‐independent. Anesthesiology 90: 1288‐1293, 1999.
 609. Sasao J, Taneyama C, Kohno N, Goto H. The effects of ketamine on renal sympathetic nerve activity and phrenic nerve activity in rabbits (with vagotomy) with and without afferent inputs from peripheral receptors. Anesth Analg 82: 362‐367, 1996.
 610. Satoh M, Minami M. Molecular pharmacology of the opioid receptors. Pharmacol Ther 68: 343‐364, 1995.
 611. Scamman FL, Ghoneim MM, Korttila K. Ventilatory and mental effects of alfentanil and fentanyl. Acta Anaesthesiol Scand 28: 63‐67, 1984.
 612. Schlame M, Hemmings HC. Inhibition by volatile anesthetics of endogenous glutamate release from synaptosomes by a presynaptic mechanism. Anesthesiology 82: 1406‐1416, 1995.
 613. Schmid K, Bohmer G, Fallert M. Medullary respiratory‐related neurons with axonal connections to rostral pons and their function in termination of inspiration. Pflugers Arch 403: 58‐65, 1985.
 614. Schneider G, Mappes A, Neissendorfer T, Schabacker M, Kuppe H, Kochs E. EEG‐based indices of anaesthesia: Correlation between bispectral index and patient state index? Eur J Anaesthesiol 21: 6‐12, 2004.
 615. Schuttler J, Stoeckel H. Clinical pharmacokinetics of alfentanyl (author's transl). Anaesthesist 31: 10‐14, 1982.
 616. Schwartz AR, Thut DC, Brower RG, Gauda EB, Roach D, Permutt S, Smith PL. Modulation of maximal inspiratory airflow by neuromuscular activity: Effect of CO2. J Appl Physiol 74: 1597‐1605, 1993.
 617. Schwilden H, Ropcke H, Drosler S. Clinical potency of nitrous oxide–is MAC the gold standard?. Anasthesiol Intensivmed Notfallmed Schmerzther 30: 337‐340, 1995.
 618. Scimemi A, Semyanov A, Sperk G, Kullmann DM, Walker MC. Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus. J Neurosci 25: 10016‐10024, 2005.
 619. Scott JC, Cooke JE, Stanski DR. Electroencephalographic quantitation of opioid effect: Comparative pharmacodynamics of fentanyl and sufentanil. Anesthesiology 74: 34‐42, 1991.
 620. Sear JW. Recent advances and developments in the clinical use of i.v. opioids during the peroperative period. Br J Anaesth 81: 38‐50, 1998.
 621. Seelagy MM, Schwartz AR, Russ DB, King ED, Wise RA, Smith PL. Reflex modulation of airflow dynamics through the upper airway. J Appl Physiol 76: 2692‐2700, 1994.
 622. Segal BS, Inman JG, Moss IR. Occlusion pressure response to inspiratory flow‐resistive loading in anesthetized swine. J Appl Physiol 71: 1774‐1779, 1991.
 623. Semyanov A, Walker MC, Kullmann DM, Silver RA. Tonically active GABA A receptors: Modulating gain and maintaining the tone. Trends Neurosci 27: 262‐269, 2004.
 624. Shaw IC, Mills GH, Turnbull D. The effect of propofol on airway pressures generated by magnetic stimulation of the phrenic nerves. Intensive Care Med 28: 891‐897, 2002.
 625. Shirahata M, Balbir A, Otsubo T, Fitzgerald RS. Role of acetylcholine in neurotransmission of the carotid body. Respir Physiol Neurobiol 157: 93‐105, 2007.
 626. Shook JE, Watkins WD, Camporesi EM. Differential roles of opioid receptors in respiration, respiratory disease, and opiate‐induced respiratory depression. Am Rev Respir Dis 142: 895‐909, 1990.
 627. Shorten GD, Opie NJ, Graziotti P, Morris I, Khangure M. Assessment of upper airway anatomy in awake, sedated and anaesthetised patients using magnetic resonance imaging. Anaesth Intensive Care 22: 165‐169, 1994.
 628. Shulman D, Bar‐yishay E, Beardsmore C, Godfrey S. Determinants of end expiratory volume in young children during ketamine or halothane anesthesia. Anesthesiology 66: 636‐640, 1987.
 629. Shulman D, Bar‐Yishay E, Godfrey S. Drive timing components of respiration in young children following induction of anaesthesia with halothane or ketamine. Can J Anaesth 35: 368‐374, 1988.
 630. Shulman D, Beardsmore CS, Aronson HB, Godfrey S. The effect of ketamine on the functional residual capacity in young children. Anesthesiology 62: 551‐556, 1985.
 631. Shyr MH, Tsai TH, Tan PP, Chen CF, Chan SH. Concentration and regional distribution of propofol in brain and spinal cord during propofol anesthesia in the rat. Neurosci Lett 184: 212‐215, 1995.
 632. Siafakas NM, Bonora M, Duron B, Gautier H, Milic‐Emili J. Dose effect of pentobarbital sodium on control of breathing in cats. J Appl Physiol 55 (5): 1582‐1592, 1983.
 633. Silverman MB, Hermes SM, Zadina JE, Aicher SA. Mu‐opioid receptor is present in dendritic targets of Endomorphin‐2 axon terminals in the nuclei of the solitary tract. Neuroscience 135: 887‐896, 2005.
 634. Sinatra RS, Sevarino FB, Paige D. Patient‐controlled analgesia with sufentanil: A comparison of two different methods of administration. J Clin Anesth 8: 123‐129, 1996.
 635. Sirois JE, Lie Q, Talley EM, Lynch C III, Bayliss DA. The TASK‐1 two‐pore domain K+ channel is a molecular substrate for neuronal effects of inhalation anesthetics. J Neurosci 201: 6347‐6354, 2000.
 636. Sirois JE, Lynch C III, Bayliss DA. Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones. J Physiol 541: 717‐729, 2002.
 637. Sirois JE, Pancrazio JJ, Lynch C III, Bayliss DA. Multiple ionic mechanisms mediate inhibition of rat motoneurones by inhalation anaesthetics. J Physiol 512: 851‐862, 1998.
 638. Sjögren D, Sollevi A, Ebberyd A, Lindahl SGE. Isoflurane anaesthesia (0.6 MAC) and hypoxic ventilatory responses in humans. Acta Anaesthesiol Scand 39: 17‐22, 1995.
 639. Smiley RM. An overview of induction and emergence characteristics of desflurane in pediatric, adult, and geriatric patients. Anesth Analg 75: S38‐S44; discussion S44‐S36, 1992.
 640. Smit JM, Bogaard JM, Goorden G, Verbraak AF, Dalinghaus P. A quasi steady state ramp method for the estimation of the ventilatory response to CO2. Respiration 59: 9‐15, 1992.
 641. Smith C, McEwan AI, Jhaveri R, Wilkinson M, Goodman D, Smith LR, Canada AT, Glass PS. The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision. Anesthesiology 81: 820‐828; discussion 826A, 1994.
 642. Smith CA, Rodman JR, Chenuel BJ, Henderson KS, Dempsey JA. Response time and sensitivity of the ventilatory response to CO2 in unanesthetized intact dogs: Central vs. peripheral chemoreceptors. J Appl Physiol 100: 13‐19, 2006.
 643. Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL. Pre‐Botzinger complex: A brainstem region that may generate respiratory rhythm in mammals. Science 254: 726‐729, 1991.
 644. Sollevi A, Lindahl SGE. Hypoxic and hypercapnic verntilatory responses during isoflurane sedation and anaesthesia in women. Acta Anaesthesiol Scand 39: 931‐938, 1995.
 645. Sonner JM, Antognini JF, Dutton RC, Flood P, Gray AT, Harris RA, Homanics GE, Kendig J, Orser B, Raines DE, Rampil IJ, Trudell J, Vissel B, Eger EI 2nd. Inhaled anesthetics and immobility: Mechanisms, mysteries, and minimum alveolar anesthetic concentration. Anesth Analg 97: 718‐740, 2003.
 646. Sonner JM, Werner DF, Elsen FP, Xing Y, Liao M, Harris RA, Harrison NL, Fanselow MS, Eger EI 2nd, Homanics GE. Effect of isoflurane and other potent inhaled anesthetics on minimum alveolar concentration, learning, and the righting reflex in mice engineered to express alpha1 gamma‐aminobutyric acid type A receptors unresponsive to isoflurane. Anesthesiology 106: 107‐113, 2007.
 647. Sood S, Morrison JL, Liu H, Horner RL. Role of endogenous serotonin in modulating genioglossus muscle activity in awake and sleeping rats. Am J Respir Crit Care Med 172: 1338‐1347, 2005.
 648. Sood S, Raddatz E, Liu X, Liu H, Horner RL. Inhibition of serotonergic medullary raphe obscurus neurons suppresses genioglossus and diaphragm activities in anesthetized but not conscious rats. J Appl Physiol 100: 1807‐1821, 2006.
 649. Soroker D, Barzilay E, Konichezky S, Bruderman I. Respiratory function following premedication with droperidol or diazepam. Anesth Analg 57: 695‐699, 1978.
 650. Spens HJ, Drummond GB. Ventilatory effects of eltanolone during induction of anaesthesia: Comparison with propofol and thiopentone. Br J Anaesth 77: 194‐199, 1996.
 651. Spens HJ, Drummond GB, Wraith PK. Changes in chest wall compartment volumes on induction of anaesthesia with eltanolone, propofol and thiopentone. Br J Anaesth 76: 369‐373, 1996.
 652. Spracklin DK, Hankins DC, Fisher JM, Thummel KE, Kharasch ED. Cytochrome P450 2E1 is the principal catalyst of human oxidative halothane metabolism in vitro. J Pharmacol Exp Ther 281: 400‐411, 1997.
 653. Steenland HW, Liu H, Horner RL. Endogenous glutamatergic control of rhythmically active mammalian respiratory motoneurons in vivo. J Neurosci 28: 6826‐6835, 2008.
 654. Steenland HW, Liu H, Sood S, Liu X, Horner RL. Respiratory activation of the genioglossus muscle involves both non‐NMDA and NMDA glutamate receptors at the hypoglossal motor nucleus in vivo. Neuroscience 138: 1407‐1424, 2006.
 655. Steffey EP, Gillespie JR, Berry JD, Eger EI 2nd, Munson ES. Anesthetic potency (MAC) of nitrous oxide in the dog, cat, and stump‐tail monkey. J Appl Physiol 36: 530‐532, 1974.
 656. Stoeckel H, Schuttler J, Magnussen H, Hengstmann JH. Plasma fentanyl concentrations and the occurrence of respiratory depression in volunteers. Br J Anaesth 54: 1087‐1095, 1982.
 657. Stoelting RK, Longnecker DE, Eger EI II. Minimum alveolar concentrations in man on awakening from methoxyflurane, halothane, ether, and fluroxene anesthesia: MAC awake. Anesthesiology 33: 5‐9, 1970.
 658. Storustovu SI, Ebert B. Pharmacological characterization of agonists at delta‐containing GABAA receptors: Functional selectivity for extrasynaptic receptors is dependent on the absence of gamma2. J Pharmacol Exp Ther 316: 1351‐1359, 2006.
 659. Streisand JB, Bailey PL, LeMaire L, Ashburn MA, Tarver SD, Varvel J, Stanley TH. Fentanyl‐induced rigidity and unconsciousness in human volunteers. Incidence, duration, and plasma concentrations. Anesthesiology 78: 629‐634, 1993.
 660. Stucke AG, Stuth AEA, Krolo M, Kampine JP, Zuperku EJ. Sevoflurane enhances overall inhibitory drive and the postsynaptic GABAA receptor response in inspiratory neurons in a decerebrate dog model. FASEB J 302‐303, 2003.
 661. Stucke AG, Stuth EAE. Mask induction with sevoflurane. In: Eike Martin and Hubert Boehrer, editors. Sevoflurane, The New Inhalational Anesthetic. Bremen: UNI‐MED Verlag, 2002, pp. 56‐60.
 662. Stucke AG, Stuth EAE, Tonkovic‐Capin V, Kampine JP, Zuperku EJ. Effects of halothane on inhibitory neurotransmission to medullary inspiratory neurons in a decerebrate dog model. Anesthesiology A1362, 2002.
 663. Stucke AG, Stuth EAE, Tonkovic‐Capin V, Kampine JP, Zuperku EJ. Sevoflurane depresses overall excitatory drive but not the postsynaptic glutamate receptor response to medullary inspiratory neurons in a decerebrate dog model. FASEB J 302‐302, 2003.
 664. Stucke AG, Stuth EAE, Tonkovic‐Capin V, Tonkovic‐Capin M, Hopp FA, Kampine JP, Zuperku EJ. Effects of sevoflurane on excitatory neurotransmission to medullary expiratory neurons and on phrenic nerve activity in a decerebrate dog model. Anesthesiology 95: 485‐491, 2001.
 665. Stucke AG, Stuth EAE, Tonkovic‐Capin V, Tonkovic‐Capin M, Hopp FA, Kampine JP, Zuperku EJ. Effects of halothane and sevoflurane on inhibitory neurotransmission to medullary expiratory neurons in a decerebrate dog model. Anesthesiology 96: 955‐962, 2002.
 666. Stucke AG, Zuperku EJ, Krolo M, Brandes IF, Hopp FA, Kampine JP, Stuth EA. Sevoflurane enhances gamma‐aminobutyric acid type A receptor function and overall inhibition of inspiratory premotor neurons in a decerebrate dog model. Anesthesiology 103: 57‐64, 2005.
 667. Stucke AG, Zuperku EJ, Sanchez A, Tonkovic‐Capin M, Tonkovic‐Capin V, Mustapic S, Stuth EA. Opioid receptors on bulbospinal respiratory neurons are not activated during neuronal depression by clinically relevant opioid concentrations. J Neurophysiol 100: 2878‐2888, 2008.
 668. Stucke AG, Zuperku EJ, Tonkovic‐Capin V, Krolo M, Hopp FA, Kampine JP, Stuth EA. Halothane enhances gamma‐aminobutyric acid receptor type A function but does not change overall inhibition in inspiratory premotor neurons in a decerebrate dog model. Anesthesiology 99: 1303‐1312, 2003.
 669. Stucke AG, Zuperku EJ, Tonkovic‐Capin V, Krolo M, Hopp FA, Kampine JP, Stuth EA. Sevoflurane depresses glutamatergic neurotransmission to brainstem inspiratory premotor neurons but not postsynaptic receptor function in a decerebrate dog model. Anesthesiology 103: 50‐56, 2005.
 670. Stucke AG, Zuperku EJ, Tonkovic‐Capin V, Tonkovic‐Capin M, Hopp FA, Kampine JP, Stuth EAE. Halothane depresses glutamatergic neurotransmission to brainstem inspiratory premotor neurons in a decerebrate dog model. Anesthesiology 98: 897‐905, 2003.
 671. Study RE. Isoflurane inhibits multiple voltage‐gated calcium currents in hippocampal pyramidal neurons. Anesthesiology 81: 104‐116, 1994.
 672. Stuth EA, Berens RJ, Staudt SR, Robertson FA, Scott JP, Stucke AG, Hoffman GM, Troshynski TJ, Tweddell JS, Zuperku EJ. The effect of caudal vs intravenous morphine on early extubation and postoperative analgesic requirements for stage 2 and 3 single‐ventricle palliation: A double blind randomized trial. Paediatr Anaesth 21: 441‐453, 2011.
 673. Stuth EA, Stucke AG, Brandes IF, Zuperku EJ. Anesthetic effects on synaptic transmission and gain control in respiratory control. Respir Physiol Neurobiol 164: 151‐159, 2008.
 674. Stuth EA, Stucke AG, Cava JR, Hoffman GM, Berens RJ. Droperidol for perioperative sedation causes a transient prolongation of the QTc time in children under volatile anesthesia. Paediatr Anaesth 14: 831‐837, 2004.
 675. Stuth EAE, Dogas Z, Krolo M, Kampine JP, Hopp FA, Zuperku EJ. Dose‐dependent effects of halothane on the phrenic nerve responses to acute hypoxia in vagotomized dogs. Anesthesiology 87: 1428‐1439, 1997a.
 676. Stuth EAE, Dogas Z, Krolo M, Kampine JP, Hopp FA, Zuperku EJ. Dose‐dependent effects of halothane on the phrenic nerve responses to carbon dioxide mediated by the carotid body chemoreceptors in vagotomized dogs. Anesthesiology 87: 1440‐1449, 1997b.
 677. Stuth EAE, Krolo M, Stucke AG, Tonkovic‐Capin M, Tonkovic‐Capin V, Hopp FA, Kampine JP, Zuperku EJ. Effects of halothane on excitatory neurotransmission to medullary expiratory neurons in a decerebrate dog model. Anesthesiology 93: 1474‐1481, 2000.
 678. Stuth EAE, Krolo M, Tonkovic‐Capin M, Hopp FA, Kampine JP, Zuperku EJ. Effects of halothane on synaptic neurotransmission to medullary expiratory neurons in the ventral respiratory group of dogs. Anesthesiology 91: 804‐814, 1999.
 679. Stuth EAE, Stucke AG, Zuperku EJ. Central effects of general anesthesia. In: Ward DS, Dahan A, Teppema LJ, editors. Pharmacology and Pathophysiology of the Control of Breathing. Boca Raton: Taylor and Francis, chap. 15, 2005, pp. 571‐652.
 680. Stuth EAE, Tonkovic‐Capin M, Kampine JP, Bajic J, Zuperku EJ. Dose‐dependent effects of halothane on the carbon dioxide responses of expiratory and inspiratory bulbospinal neurons and the phrenic nerve activities in dogs. Anesthesiology 81: 1470‐1483, 1994.
 681. Stuth EAE, Tonkovic‐Capin M, Kampine JP, Zuperku EJ. Dose‐dependent effects of isoflurane on the CO2 responses of expiratory medullary neurons and the phrenic nerve activities in dogs. Anesthesiology 76: 763‐774, 1992.
 682. Sundman E, Witt H, Sandin R, Kuylenstierna R, Boden K, Ekberg O, Eriksson LI. Pharyngeal function and airway protection during subhypnotic concentrations of propofol, isoflurane, and sevoflurane: Volunteers examined by pharyngeal videoradiography and simultaneous manometry. Anesthesiology 95: 1125‐1132, 2001.
 683. Swart EL, de Jongh J, Zuideveld KP, Danhof M, Thijs LG, Strack van Schijndel RJ. Population pharmacokinetics of lorazepam and midazolam and their metabolites in intensive care patients on continuous venovenous hemofiltration. Am J Kidney Dis 45: 360‐371, 2005.
 684. Sztark F, Chopin F, Bonnet A, Cros AM. Concentration of remifentanil needed for tracheal intubation with sevoflurane at 1 MAC in adult patients. Eur J Anaesthesiol 22: 919‐924, 2005.
 685. Tabatabai M, Kitahata LM, Kawahara M, Collins JG. Enflurane depresses activity of the medullary inspiratory neurons in the cat. Proc Soc Exp Biol and Med 195: 79‐83, 1990.
 686. Tabatabai M, Kitahata LM, Yuge O, Matsumoto M, Collins JG. Effects of halothane on medullary inspiratory neurons of the cat. Anesthesiology 66: 176‐180, 1987.
 687. Takakura AC, Moreira TS, Stornetta RL, West GH, Gwilt JM, Guyenet PG. Selective lesion of retrotrapezoid Phox2b‐expressing neurons raises the apneic threshold in rats. J Physiol 586: 2971‐2991, 2008.
 688. Takeda R, Haji A. Microiontophoresis of flurazepam on inspiratory and postinspiratory neurons in the ventrolateral medulla of cats: an intracellular study in vivo. NeurosciLett 102: 261‐267, 1989.
 689. Takeda R, Haji A. Effects of halothane on membrane potential and discharge activity in pairs of bulbar respiratory neurons of decerebrate cats. Neuropharm 31: 1049‐1058, 1992.
 690. Takeda R, Haji A. Cellular effects of isoflurane on bulbar respiratory neurons in decerebrate cats. Jpn J Pharmacol 62: 57‐65, 1993a.
 691. Takeda R, Haji A. Mechanisms underlying post‐inspiratory depolarization in post‐inspiratory neurons of the cat. Neurosci Lett 150: 1‐4, 1993b.
 692. Takeda R, Haji A, Hukuhara T. Diazepam potentiates postsynaptic inhibition in bulbar respiratory neurons of cats. Respir Physiol 77: 173‐186, 1989.
 693. Takeda R, Haji A, Hukuhara T. Selective actions of anesthetic agents on membrane potential trajectory in bulbar respiratory neurons of cats. Pfluegers Arch 416: 375‐384, 1990.
 694. Takeda S, Eriksson LI, Yamamoto Y, Joensen H, Onimaru H, Lindahl SGE. Opioid action on respiratory neuron activity of the isolated respiratory network in newborn rats. Anesthesiology 95: 740‐749, 2001.
 695. Takizawa E, Hiraoka H, Takizawa D, Goto F. Changes in the effect of propofol in response to altered plasma protein binding during normothermic cardiopulmonary bypass. Br J Anaesth 96: 179‐185, 2006.
 696. Talley EM, Bayliss DA. Modulation of TASK‐1 (Kcnk3) and TASK‐3 (Kcnk9) potassium channels: Volatile anesthetics and neurotransmitters share a molecular site of action. J Biol Chem 277: 17733‐17742, 2002.
 697. Talley EM, Lei Q, Sirois JE, Bayliss DA. TASK‐1, a two‐pore domain K channel, is modulated by multiple neurotransmitters in motoneurons. Neuron 25: 399‐410, 2000.
 698. Talley EM, Solórzano G, Lei L, Kim D, Bayliss DA. CNS distribution of members of the two‐pore‐domain (KCNK) potassium channel family. J Neurosci 21: 7491‐7505, 2001.
 699. Tanabe A, Fujii T, Onimaru H. Facilitation of respiratory rhythm by a mu‐opioid agonist in newborn rat pons‐medulla‐spinal cord preparations. Neurosci Lett 375: 19‐22, 2005.
 700. Tanelian DL, Kosek P, Mody I, Maclver MB. The role of the GABAA receptor/chloride channel complex in anesthesia. Anesthesiology 78 (4): 757‐776, 1993.
 701. Tassonyi E, Charpantier E, Muller D, Dumont L, Bertrand D. The role of nicotinic acetylcholine receptors in the mechanisms of anesthesia. Brain Res 57: 133‐150, 2002.
 702. Taylor MB, Grounds RM, Mulrooney PD, Morgan M. Ventilatory effects of propofol during induction of anaesthesia. Comparison with thiopentone. Anaesthesia 41: 816‐820, 1986.
 703. Taylor PM, Robertson SA, Dixon MJ, Ruprah M, Sear JW, Lascelles BD, Waters C, Bloomfield M. Morphine, pethidine and buprenorphine disposition in the cat. J Vet Pharmacol Ther 24: 391‐398, 2001.
 704. Taylor RH, Lerman J. Induction, maintenance and recovery characteristics of desflurane in infants and children. Can J Anaesth 39: 6‐13, 1992.
 705. Temp JA, Henson LC, Ward DS. Does a subanesthetic concentration of isoflurane blunt the ventilatory response to hypoxia? Anesthesiology 77: 1116‐1124, 1992.
 706. Temp JA, Henson LC, Ward DS. Effect of a subanesthetic minimum alveolar concentration of isoflurane on two tests of the hypoxic ventilatory response. Anesthesiology 80: 739‐750, 1994.
 707. Temp JA, Henson LC, Ward DS. Subanesthetic isoflurane and the ventilatory response to hypoxemia (reply). Anesthesiology 78: 1190‐1192, 1993.
 708. Teppema LJ, Romberg RR, Dahan A. Antioxidants reverse reduction of the human hypoxic ventilatory response by subanesthetic isoflurane. Anesthesiology 102: 747‐753, 2005.
 709. Teppema LJ, van Dorp E, Mousavi Gourabi B, van Kleef JW, Dahan A. Differential effect of morphine and morphine‐6‐glucuronide on the control of breathing in the anesthetized cat. Anesthesiology 109: 689‐697, 2008.
 710. Todd MM, Drummond JC, HS U. The hemodynamic consequences of high‐dose methohexital anesthesia in humans. Anesthesiology 61: 495‐501, 1984.
 711. Tonkovic‐Capin M, Krolo M, Stuth EAE, Hopp FA, Zuperku EJ. Improved method of canine decerebration. J Appl Physiol 85: 747‐750, 1998.
 712. Tonkovic‐Capin V, Stucke AG, Stuth EA, Tonkovic‐Capin M, Krolo M, Hopp FA, McCrimmon DR, Zuperku EJ. Differential modulation of respiratory neuronal discharge patterns by GABAA receptor and apamin‐sensitive K+ channel antagonism. J Neurophysiol 86: 2363‐2373, 2001.
 713. Tosun Z, Akin A, Guler G, Esmaoglu A, Boyaci A. Dexmedetomidine‐ketamine and propofol‐ketamine combinations for anesthesia in spontaneously breathing pediatric patients undergoing cardiac catheterization. J Cardiothorac Vasc Anesth 20: 515‐519, 2006.
 714. Trouth CO, Millis RM, Bernard DG, Pan Y, Whittaker JA, Archer PW. Cholinergic‐opioid interactions at brainstem respiratory chemosensitive areas in cats. Neurotoxicology 14: 459‐467, 1993.
 715. Tusiewicz K, Bryan AC, Froese AB. Contributions of changing rib cage‐diaphragm interactions to the ventilatory depression of halothane anesthesia. Anesthesiology 47: 327‐337, 1977.
 716. Urban BW. Current assessment of targets and theories of anaesthesia. Br J Anaesth 89: 167‐183, 2002.
 717. Urban BW, Duch DS, Frenkel C, Rehberg B, Wartenberg HC. Do general anesthetics act on specific receptors?. Anasthesiol Intensivmed Notfallmed Schmerzther 30: 375‐382, 1995.
 718. Usher AG, Kearney RA, Tsui BC. Propofol total intravenous anesthesia for MRI in children. Paediatr Anaesth 15: 23‐28, 2005.
 719. Valley RD, Freid EB, Bailey AG, Kopp VJ, Georges LS, Fletcher J, Keifer A. Tracheal extubation of deeply anesthetized pediatric patients: A comparison of desflurane and sevoflurane. Anesth Analg 96: 1320‐1324, 2003.
 720. van den Elsen M, Dahan A, Berkenbosch A, DeGoede J, van Kleef JW, Olievier ICW. Does subanesthetic isoflurane affect the ventilatory response to acute isocapnic hypoxia in healthy volunteers? Anesthesiology 81: 860‐867, 1994.
 721. van den Elsen MJLJ, Dahan A, DeGoede J, Berkenbosch A, van Kleef J. Influences of subanaesthetic isoflurane on ventilatory control in humans. Anesthesiology 83: 478‐490, 1995.
 722. van den Hoogen RH, Bervoets KJ, Colpaert FC. Respiratory effects of epidural and subcutaneous morphine, meperidine, fentanyl and sufentanil in the rat. Anesth Analg 67: 1071‐1078, 1988.
 723. van den Nieuwenhuyzen MC, Engbers FH, Burm AG, Lemmens HJ, Vletter AA, van Kleef JW, Bovill JG. Computer‐controlled infusion of alfentanil for postoperative analgesia. A pharmacokinetic and pharmacodynamic evaluation. Anesthesiology 79: 481‐492; discussion 427A, 1993.
 724. van Dissel JT, Berkenbosch A, Olievier CN, DeGoede J, Quanjer PH. Effects of halothane on the ventilatory response to hypoxia and hypercapnia in cats. Anesthesiology 62: 448‐456, 1985.
 725. Van Hamme MJ, Ghoneim MM, Ambre JJ. Pharmacokinetics of etomidate, a new intravenous anesthetic. Anesthesiology 49: 274‐277, 1978.
 726. Vangerven M, Van Hemelrijck J, Wouters P, Vandermeersch E, Van Aken H. Light anaesthesia with propofol for paediatric MRI. Anaesthesia 47: 706‐707, 1992.
 727. Vanini G, Watson CJ, Lydic R, Baghdoyan HA. Gamma‐aminobutyric acid‐mediated neurotransmission in the pontine reticular formation modulates hypnosis, immobility, and breathing during isoflurane anesthesia. Anesthesiology 109: 978‐988, 2008.
 728. Viana F, Bayliss DA, Berger AJ. Repetitive firing properties of developing rat brainstem motoneurones. J Physiol 486: 745‐761, 1995.
 729. Violet JM, Downie DL, Nakisa RC, Lieb WR, Franks NP. Differential sensitivities of mammalian neuronal and muscle nicotinic acetylcholine receptors to general anesthetics. Anesthesiology 86: 866‐874, 1997.
 730. Visser K, Hassink EA, Bonsel GJ, Moen J, Kalkman CJ. Randomized controlled trial of total intravenous anesthesia with propofol versus inhalation anesthesia with isoflurane‐nitrous oxide: Postoperative nausea with vomiting and economic analysis. Anesthesiology 95: 616‐626, 2001.
 731. Viswanathan S, Campbell CE, Cork RC. Asymptomatic undetected mediastinal mass: A death during ambulatory anesthesia. J Clin Anesth 7: 151‐155, 1995.
 732.von Ungern‐Sternberg BS, Frei FJ, Hammer J, Schibler A, Doerig R, Erb TO. Impact of depth of propofol anaesthesia on functional residual capacity and ventilation distribution in healthy preschool children. Br J Anaesth 98: 503‐508, 2007.
 733. Waldhoer M, Bartlett SE, Whistler JL. Opioid receptors. Annu Rev Biochem 73: 953‐990, 2004.
 734. Wamsley JK, Zarbin MA, Young WS 3rd, Kuhar MJ. Distribution of opiate receptors in the monkey brain: An autoradiographic study. Neuroscience 7: 595‐613, 1982.
 735. Wang QP, Zadina JE, Guan JL, Shioda S. Morphological evidence of endomorphin as an agonist for the mu‐opioid receptor in the rat spinal cord. Neurosci Lett 341: 107‐110, 2003.
 736. Wang W, Tiwari JK, Bradley SR, Zaykin RV, Richerson GB. Acidosis‐stimulated neurons of the medullary raphe are serotonergic. J Neurophysiol 85: 2224‐2235, 2001.
 737. Wang Y, Jordan D, Ramage AG. Both GABAA and GABAB receptors mediate vagal inhibition in nucleus tractus solitarii neurones in anaesthetized rats. Auton Neurosci 152: 75‐83.
 738. Ward DS. Stimulation of hypoxic ventilatory drive by droperidol. AnesthAnalg 63: 106‐110, 1984.
 739. Ward DS, Berkenbosch A, DeGoede J, Olievier CN. Dynamics of the ventilatory response to central hypoxia in cats. J Appl Physiol 68: 1107‐1113, 1990.
 740. Ward DS, Dahan A, Mann CB. Modelling the dynamic ventilatory response to hypoxia in humans. Ann Biomed Eng 20: 181‐194, 1992.
 741. Warley A, Clarke M, Phillips T, Stradling J. Ventilatory response to an inhaled constant CO2 load and added dead space in healthy men, awake and asleep. Respir Physiol 75: 183‐191, 1989.
 742. Warner DO. General anesthesia and respiratory mechanics. In: Denham S, Ward AD, Teppema LJ, editors. Pharmacology and Pathophysiology of the Control of Breathing. Boca Raton, FL: Taylor & Francis Group, 2005, pp. 687‐736.
 743. Warner DO, Joyner MJ, Ritman EL. Anesthesia and chest wall function in dogs. J Appl Physiol 76: 2802‐2813, 1994.
 744. Warner DO, Joyner MJ, Ritman EL. Chest wall responses to rebreathing in halothane‐anesthetized dogs. Anesthesiology 83: 835‐843, 1995.
 745. Warner DO, Warner MA. Human chest wall function while awake and during halothane anesthesia II. Carbon dioxide rebreathing. Anesthesiology 82: 20‐31, 1995.
 746. Warner DO, Warner MA, Joyner MJ, Ritman EL. The effect of nitrous oxide on chest wall function in humans and dogs. Anesth Analg 86: 1058‐1064, 1998.
 747. Warner DO, Warner MA, Ritman EL. Human chest wall function while awake and during halothane anesthesia I. Quiet breathing. Anesthesiology 82: 6‐19, 1995.
 748. Warner DO, Warner MA, Ritman EL. Mechanical significance of respiratory muscle activity in humans during halothane anesthesia. Anesthesiology 84: 309‐321, 1996.
 749. Washburn CP, Sirois JE, Talley EM, Guyenet PG, Bayliss DA. Serotonergic raphe neurons express TASK channel transcripts and a TASK‐like pH‐ and halothane‐sensitive K+ conductance. J Neurosci 22: 1256‐1265, 2002.
 750. Watts SJ, Slocombe RF, Harbison WD, Stewart GA. Assessment of analgesia and other effects of morphine and thiambutene in the mouse and cat. Aust Vet J 49: 525‐529, 1973.
 751. Weil JV, McCullough RE, Kline JS, Sodal IE. Diminished ventilatory response to hypoxia and hypercapnia after morphine in normal man. N Engl J Med 292: 1103‐1106, 1975.
 752. Westmoreland CL, Sebel PS, Gropper A. Fentanyl or alfentanil decreases the minimum alveolar anesthetic concentration of isoflurane in surgical patients. Anesth Analg 78: 23‐28, 1994.
 753. Westphalen RI, Hemmings HC. Effects of isoflurane and propofol on glutamate and GABA transporters in isolated cortical nerve terminals. Anesthesiology 98: 364‐372, 2003.
 754. Westphalen RI, Hemmings HC Jr. Volatile anesthetic effects on glutamate versus GABA release from isolated rat cortical nerve terminals: Basal release. J Pharmacol Exp Ther 316: 208‐215, 2006.
 755. Wheatley JR, Kelly WT, Tully A, Engel LA. Pressure‐diameter relationships of the upper airway in awake supine subjects. J Appl Physiol 70: 2242‐2251, 1991.
 756. Wheatley JR, Tangel DJ, Mezzanotte WS, White DP. Influence of sleep on response to negative airway pressure of tensor palatini muscle and retropalatal airway. J Appl Physiol 75: 2117‐2124, 1993.
 757. Whitehurst SL, Nemoto EM, Yao L, Yonas H. MAC of xenon and halothane in rhesus monkeys. J Neurosurg Anesthesiol 6: 275‐279, 1994.
 758. Whitelaw WA, Derenne JP. Airway occlusion pressure. J Appl Physiol 74: 1475‐1483, 1993.
 759. Wilder RT, Flick RP, Sprung J, Katusic SK, Barbaresi WJ, Mickelson C, Gleich SJ, Schroeder DR, Weaver AL, Warner DO. Early exposure to anesthesia and learning disabilities in a population‐based birth cohort. Anesthesiology 110: 796‐804, 2009.
 760. Willette RN, Krieger AJ, Sapru HN. Opioids increase laryngeal resistance and motoneuron activity in the recurrent laryngeal nerve. Eur J Pharmacol 80: 57‐63, 1982.
 761. Withington‐Wray DJ, Mifflin SW, Spyer KM. Intracellular analysis of respiratory‐modulated hypoglossal motoneurons in the cat. Neuroscience 25: 1041‐1051, 1988.
 762. Woch G, Kubin L. Non‐reciprocal control of rhythmic activity in respiratory‐modulated XII motoneurons. Neuroreport 6: 2085‐2088, 1995.
 763. Wodey E, Pladys P, Copin C, Lucas MM, Chaumont A, Carre P, Lelong B, Azzis O, Ecoffey C. Comparative hemodynamic depression of sevoflurane versus halothane in infants. Anesthesiology 87: 795‐800, 1997.
 764. Wu J, Harata N, Akaike N. Potentiation by sevoflurane of the γ‐aminobutyric acid‐induced chloride current in acutely dissociated CA1 pyramidal neurones from rat hippocampus. Br J Pharmac 119: 1013‐1021, 1996.
 765. Xia Y, Haddad GG. Major difference in the expression of delta‐ and mu‐opioid receptors between turtle and rat brain. J Comp Neurol 436: 202‐210, 2001.
 766. Xu F, Sarti P, Zhang J, Blanck TJJ. Halothane and isoflurane alter calcium dynamics in rat cerebrocortical synaptosomes. Anesth Analg 87: 701‐710, 1998.
 767. Yamakage M, Kamada Y, Toriyabe M, Honma Y, Namiki A. Changes in respiratory pattern and arterial blood gases during sedation with propofol or midazolam in spinal anesthesia. J Clin Anesth 11: 375‐379, 1999.
 768. Yamakura T, Bertaccini E, Trudell JR, Harris RA. Anesthetics and ion channels: Molecular models and sites of action. Annu Rev Pharmacol Toxicol 41: 23‐51, 2001.
 769. Yamakura T, Chavez‐Noriega LE, Harris RA. Subunit‐dependent inhibition of human neuronal nicotinic acetylcholine receptors and other ligand‐gated ion channels by dissociative anesthetics ketamine and dizocilpine. Anesthesiology 92: 1144‐1153, 2000.
 770. Yamakura T, Harris RA. Effects of gaseous anesthetics nitrous oxide and xenon on ligand‐gated ion channels. Anesthesiology 93: 1095‐1101, 2000.
 771. Yamakura T, Sakimura K, Shimoji K, Mishina M. Effects of propofol on various AMPA‐, kainate‐ and NMDA‐selective glutamate receptor channels expressed in Xenopus oocytes. Neurosci Lett 188: 187‐190, 1995.
 772. Yassen A, Kan J, Olofsen E, Suidgeest E, Dahan A, Danhof M. Mechanism‐based pharmacokinetic‐pharmacodynamic modeling of the respiratory‐depressant effect of buprenorphine and fentanyl in rats. J Pharmacol Exp Ther 319: 682‐692, 2006.
 773. Yassen A, Olofsen E, Kan J, Dahan A, Danhof M. Pharmacokinetic‐pharmacodynamic modeling of the effectiveness and safety of buprenorphine and fentanyl in rats. Pharm Res 25: 183‐193, 2008.
 774. Yassen A, Olofsen E, Romberg R, Sarton E, Teppema L, Danhof M, Dahan A. Mechanism‐based PK/PD modeling of the respiratory depressant effect of buprenorphine and fentanyl in healthy volunteers. Clin Pharmacol Ther 81: 50‐58, 2007.
 775. Yokota S, Tsumori T, Ono K, Yasui Y. Glutamatergic pathways from the Kolliker‐Fuse nucleus to the phrenic nucleus in the rat. Brain Res 995: 118‐130, 2004.
 776. Yost CS. Tandem pore domain K channels: An important site of volatile anesthetic action? Curr Drug Targets 1: 207‐217, 2000.
 777. Yost CS. Update on tandem pore (2P) domain K+ channels. Curr Drug Targets 4: 347‐351, 2003.
 778. Zakko SF, Seifert HA, Gross JB. A comparison of midazolam and diazepam for conscious sedation during colonoscopy in a prospective double‐blind study. Gastrointest Endosc 49: 684‐689, 1999.
 779. Zhang M, Buttigieg J, Nurse CA. Neurotransmitter mechanisms mediating low‐glucose signalling in cocultures and fresh tissue slices of rat carotid body. J Physiol 578: 735‐750, 2007.
 780. Zhang M, Clarke K, Zhong H, Vollmer C, Nurse CA. Postsynaptic action of GABA in modulating sensory transmission in co‐cultures of rat carotid body via GABA(A) receptors. J Physiol 587: 329‐344, 2009.
 781. Zhang M, Nurse CA. CO2/pH chemosensory signaling in co‐cultures of rat carotid body receptors and petrosal neurons: Role of ATP and ACh. J Neurophysiol 92: 3433‐3445, 2004.
 782. Zhang XJ, Yu G, Wen XH, Lin ZC, Yang FQ, Zheng ZG, Chen RC, Zhong NS. Effect of propofol on twitch diaphragmatic pressure evoked by cervical magnetic stimulation in patients. Br J Anaesth 102: 61‐64, 2009.
 783. Zhang Y, Laster MJ, Hara K, Harris RA, Eger EI 2nd, Stabernack CR, Sonner JM. Glycine receptors mediate part of the immobility produced by inhaled anesthetics. Anesth Analg 96: 97‐101, table of contents, 2003.
 784. Zhang Y, Wu S, Eger EI 2nd, Sonner JM. Neither GABA(A) nor strychnine‐sensitive glycine receptors are the sole mediators of MAC for isoflurane. Anesth Analg 92: 123‐127, 2001.
 785. Zhang Z, Xu F, Zhang C, Liang X. Activation of opioid mu receptors in caudal medullary raphe region inhibits the ventilatory response to hypercapnia in anesthetized rats. Anesthesiology 107: 288‐297, 2007.
 786. Zhu W, Pan ZZ. Synaptic properties and postsynaptic opioid effects in rat central amygdala neurons. Neuroscience 127: 871‐879, 2004.
 787. Zornow MH. Clinical testing of the apnea prevention device: Proof of concept data. Anesth Analg 112: 582‐586.
 788. Zuperku EJ, Brandes IF, Stucke AG, Hopp FA, Stuth EAE. Characteristics of drug concentration profiles for picoejection studies of brainstem neurons. FASEB J C572, 2006.
 789. Zuperku EJ, Brandes IF, Stucke AG, Sanchez A, Hopp FA, Stuth EA. Major components of endogenous neurotransmission underlying the discharge activity of hypoglossal motoneurons in vivo. In: Poulin MJ, Wilson RJA, editors. Integration in Respiratory Control ‐ from Genes to Systems (Advances in Experimental Medicine and Biology Series Volume 605). New York: Springer Science+Business Media, LLC, 2008, 605, pp. 279‐284
 790. Zuperku EJ, Coon RL, Bosnjak ZJ, Igler FO, Kampine JP. Pulmonary effects of halothane on the breathing pattern. Proc ASA Ann Mtg 209‐210, 1976.
 791. Zuperku EJ, McCrimmon DR. Gain modulation of respiratory neurons. Respir Physiol Neurobiol 131: 121‐133, 2002.
 792. Zwass MS, Fisher DM, Welborn LG, Cote CJ, Davis PJ, Dinner M, Hannallah RS, Liu LM, Sarner J, McGill WA, et al. Induction and maintenance characteristics of anesthesia with desflurane and nitrous oxide in infants and children. Anesthesiology 76: 373‐378, 1992.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control
 

How to Cite

Eckehard A.E. Stuth, Astrid G. Stucke, Edward J. Zuperku. Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control. Compr Physiol 2012, 2: 2281-2367. doi: 10.1002/cphy.c100061