Diaphragmatic function during sevoflurane anaesthesia in dogs

The effect of increasing the concentration of sevoflurane anaesthesia on diaphragmatic function was investigated in six mechanically ventilated dogs. Diaphragmatic function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal stimulation of the cervical phrenic nerves at frequencies of 0.5, 10, 20, 50, and 100 Hz under quasi-isometric conditions. Measurements were performed at 1, 1.5 and 2 MAC concentrations after maintaining stable conditions for one hour. The Pdi-stimulus frequency relationship was compared at each anaesthetic concentration. The sequence of changing anaesthetic depth was altered in random fashion among animals. The Pdi amplitude generated by single twitch (0.5 Hz) was unchanged at the three concentrations. In addition, no change in Pdi during 10, 20, 50 Hz stimulation was noted at any of the three levels of anaesthesia. By contrast, Pdi with 100 Hz stimulation during 2 MAC sevoflurane exposure (28.1 +/- 5.0 cmH2O) decreased below Pdi levels seen at 1 and 1.5 MAC (35.3 +/- 4.3 cmH2O and 31.5 +/- 4.3 cmH2O, respectively) (P less than 0.05). From these results, we conclude that sevoflurane impairs diaphragmatic function in deep anaesthesia.     

Effects of isoflurane on contractile properties of diaphragm

Isoflurane has been shown to depress skeletal muscle force in vitro, but data are not available regarding the effects of isoflurane on diaphragmatic muscle function in vivo. To answer this question, 15 rats anesthetized with pentobarbital and mechanically ventilated were studied. They were divided into three groups of five animals each, according to the administered concentration of isoflurane. Diaphragmatic function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal phrenic nerve stimulation at 0.5 Hz, 20 Hz, 50 Hz, and 100 Hz under quasi-isometric conditions. After a control measurement (C), isoflurane was administered at a constant concentration (0.5, 1, or 1.5 MAC) and Pdi measurements were repeated after 30 min of isoflurane exposure (T1) and 30 min after discontinuing isoflurane (T2). In the group breathing 1.5 MAC isoflurane, the time constant of diaphragmatic relaxation (tau) and integrated electrical activity of the diaphragm (Edi) were also assessed. The Pdi amplitude generated by single twitch (0.5 Hz) was unchanged at the three isoflurane concentrations. A significant increase in Pdi at 20 Hz was observed at T1, which returned to control after 30 min recovery (T2). No change in Pdi during 50 Hz stimulation was noted during 0.5 and 1 MAC isoflurane exposure, whereas it was reduced at T1 during 1.5 MAC. For 100 Hz stimulation, a significant decrease in Pdi was noted for all groups at T1, which returned toward control values at T2. Edi was markedly reduced for 50 and 100 Hz stimulation, but this reduction was also transient, since Edi returned toward control values at T2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of sevoflurane on diaphragmatic contractility in dogs.

The effect of sevoflurane on diaphragmatic contractility was investigated in 12 anesthetized, mechanically ventilated dogs with the thorax opened. Animals were divided into two groups of six each: the sevoflurane and time control groups. We assessed contractility by the transdiaphragmatic pressure (Pdi) during supramaximal stimulation of the phrenic nerve at frequencies of 0.5, 10, 20, 50, and 100 Hz under quasiisometric conditions. The integrated electrical activity (Edi) of the crural and costal parts of the diaphragm (Edi cru, Edi cost) was also measured. In the sevoflurane group, diaphragmatic contractility was determined during three levels of anesthesia, specifically 0, 1.0, and 1.5 minimum alveolar anesthetic concentration (MAC). Measurements were made at the start of the stimulation (initial) and at the end of the 2-s period (2-s). Increasing the depth of sevoflurane anesthesia did not cause any significant differences in Pdi and Edi at 0.5-, 10-, and 20-Hz stimulation. By contrast, at 50- and 100-Hz stimulation, initial Pdi during 1.0 and 1.5 MAC sevoflurane exposure decreased significantly compared with the 0 MAC value (P less than 0.05). In addition, there was a statistical difference in 2-s Pdi between 1.0 and 1.5 MAC at 100-Hz stimulation (P less than 0.05). The Edi cru showed similar changes in Pdi at both measurements, whereas there was no remarkable change in Edi cost. There was no significant change either in Pdi or in Edi with respect to time in the time control group. We conclude from these results that sevoflurane impairs diaphragmatic contractility through its inhibitory effect on neuromuscular transmission, predominantly of the crural part.     

Different effects of halothane and enflurane on diaphragmatic contractility in vivo

We examined the effects of halothane and enflurane on diaphragmatic contractility in 12 anesthetized, mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Animals were randomly assigned to two groups, a halothane group (n = 6) and an enflurane group (n = 6). The Pdi stimulus-frequency relationship was compared at anesthetic levels of 1, 1.5, and 2 MAC (minimum alveolar concentration) in each group. The sequence of changing anesthetic concentration was randomized. In addition, the Pdi-frequency relationship was also compared between 1 MAC of halothane and enflurane in 8 of 12 dogs. In animals anesthetized with enflurane, Pdi significantly decreased with 50- and 100-Hz stimulation in the presence of increasing MAC values, whereas Pdi at 10-Hz stimulation was not affected by the depth of anesthesia. Pdi with 20-Hz stimulation during 2 MAC enflurane also decreased significantly below Pdi levels seen at 1 and 1.5 MAC. By contrast, with halothane there was no difference in Pdi at any of the stimulation frequencies during any of the three levels of anesthesia. There was no statistical difference, however, between Pdi-frequency relationships during 1 MAC of halothane and enflurane in eight animals. From these results, we conclude that halothane does not impair diaphragmatic contractility any more than enflurane does, but enflurane decreases force generation of the diaphragm at high stimulation frequencies in a dose-related fashion. This depressant effect of enflurane occurs mainly through the impairment of neuromuscular transmission and/or membrane excitability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enflurane impairs canine diaphragmatic contractilityin vivo

We examined the effect of enflurane on diaphragmatic contractility in six anesthetized mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Pdi-stimulus frequency relationship was compared at three levels of anesthesia, namely 1, 1.5, and 2 MAC (minimum alveolar concentration) of enflurane. The sequence of changing anesthetic concentration was randomized between animals. Pdi at 50 and 100Hz stimulation was significantly decreased with increasing MAC while Pdi at 10Hz stimulation was not affected by the depth of anesthesia. Pdi of 20Hz stimulation was significantly decreased at 2 MAC as compared to those at 1 and 1.5 MAC. We conclude that enflurane decreases contractility of the diaphragm mainly through impairment of the neuromuscular transmission and/or membrane excitability. Part of its effects is, however, probably related to the impairment of excitation-contraction coupling, as suggested by the depression of Pdi at 2 MAC in response to 20Hz stimulation.(Kochi T, Ide T, Isono S et al.: Enflurane impairs canine diaphragmatic contractility in vivo. J Anesth 4: 226–231, 1990)     

EnHurane supresses phrenic nerve-diaphragm Transmissionin vivo

We examined the effects of enflurane on the diaphragmatic function in 15 pentobarbital-anesthetized, mechanically ventilated dogs. They were divided into three groups of five animals each, according to the administered concentration of enflurane. The diaphragmatic function was assessed from transdiaphragmatic pressure (Pdi) and integrated diaphragmatic electromyography (Edi) developed at functional residual capacity against an occluded airway during bilateral supramaximal phrenic nerve stimulation at 0.5, 10, 20, 50 and 100Hz under quasiisometric condition. After a control measurement, enflurane was administered at a constant end-expired concentration (0, 0.5 and 1MAC) and the measurement was repeated after 1 hour of exposure. The Pdi amplitude generated by single twitch (0.5Hz) and during 10, 20 and 50Hz stimulation was unchanged between the groups. No change in Pdi during 100Hz stimulation was noted during 0 and 0.5MAC exposure, while it was reduced by 1MAC of enflurane. When the values of Pdi were expressed as % of maximum Pdi (%Pdi,max) that developed during control measurement and analyzed in terms of %Pdi,max—stimulus frequency relationship, a significant decrease in %Pdi,max was noted for 100Hz stimulation in 0.5 and 1MAC groups compared to the control. Similarly, Edi during 100Hz stimulation obtained in 0.5 and 1MAC groups was markedly depressed compared to the control. Edi during 50Hz stimulation was also decreased at 1MAC. Relative changes in Edi following enflurane administration were greater than the corresponding changes of Pdi. These results demonstrate that enflurane impairs diaphragmatic function through its inhibitory effects on neuromuscular transmission.(Kochi T, Ide T, Isono S, et al.: Enflurane supresses phrenic nerve-diaphragm transmission in vivo. J Anesth 5: 260–267, 1991)     

The influence of halothane, isoflurane and sevoflurane on rocuronium infusion in children

BACKGROUND: Rocuronium is a non-depolarizing neuromuscular blocking agent with intermediate duration of action and without significant cumulative properties, suitable for continuous infusion. This study was designed to determine the infusion requirements in children under nitrous oxide and fentanyl, halothane, isoflurane or sevoflurane anaesthesia. METHODS: Forty children, 3-11 years old, ASA physical status group I or II were studied. They were randomly allocated to receive fentanyl-nitrous oxide, 1 MAC halothane-nitrous oxide, 1 MAC isoflurane-nitrous oxide or 1 MAC sevoflurane-nitrous oxide anaesthesia. Rocuronium, 0.6 mg(-1) was used to facilitate endotracheal intubation. Electromyographic response of adductor pollicis to train-of-four (TOF) stimulation, 2 Hz for 2 s, applied to the ulnar nerve at 10-s intervals was recorded using Relaxograph (Datex, Helsinki, Finland). Once the first twitch response (T1) returned to 5%, muscle relaxation was maintained by continuous infusion of rocuronium, adjusted automatically in a closed-loop system to maintain a stable 90-99% T1 depression. The block was considered stable if it changed by no more than 2% over a 10-min observation period. RESULTS: Halothane, isoflurane and sevoflurane groups had ower infusion requirements than the fentanyl-nitrous oxide group (P<0.00075). Rocuronium requirement (mean +/- SD) at one hour from the commencement of anaesthesia was 16.7+/-2.3, 13.6+/-3.7, 13.1+/-5.1 and 8.4+/-1.6 microg x kg(-1) x min(-1) for children receiving fentanyl-nitrous oxide, halothane, isoflurane and sevoflurane anaesthesia, respectively. CONCLUSIONS: The rocuronium infusion rate required to maintain stable 90-99% T1 depression was reduced by approximately 20% with halothane and isoflurane anaesthesia, and by 50% with evoflurane anaesthesia when compared to fentanyl-nitrous oxide anaesthesia. Significant patient-to-patient variability of infusion rate makes monitoring of neuromuscular transmission necessary.     

Measurement of twitch transdiaphragmatic pressure: surface versus needle electrode stimulation.

The transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal phrenic nerve stimulation at 1 Hz from surface stimulating electrodes was compared with pressures obtained from needle electrodes inserted under local anaesthesia. Surface electrodes were used to obtain diaphragmatic electromyograms and magnetometers to monitor rib cage and abdominal configuration. Twitch Pdi was recorded at functional residual capacity in three normal subjects. Mean (SD) twitch Pdi in the three subjects during stimulation with surface electrodes was 19.4 (1.8), 22.5 (1.1), and 29.3 (2.2) cm H2O compared with 12.9 (1.5), 17:4 (1.3), and 22.6 (3.0) cm H2O with needle stimulating electrodes. Thus phrenic nerve stimulation with needle electrodes was more complicated and more invasive than stimulation with surface electrodes and resulted in lower transdiaphragmatic pressures.     

The onset of ablation of the evoked adductor pollicis muscle twitch in children: a clinical perspective

The time to loss of the adductor pollicis muscle response to ulnar nerve stimulation at 1 Hz (twitch) after succinylcholine, 1.5 mg.kg-1 intravenously (IV), or vecuronium, 0.1 mg.kg-1 (IV), administration was assessed visually in 134 children, age 2-13 yr, during clinically determined, deep halothane, enflurane and isoflurane anaesthesia. The overall time to twitch ablation and duration of succinylcholine's action is in agreement with published times obtained under controlled experimental conditions; the onset time following vecuronium is comparable to those observed during a similar anaesthetic background measured under controlled experimental conditions. Twitch ablation after succinylcholine was achieved in half the time needed following vecuronium regardless of anaesthetic agent. Succinylcholine's and vecuronium's onset time as well as succinylcholine's duration is adequately assessed by the outlined, simple clinical means. The choice of inhalation agent does not affect the time to visible twitch ablation in a clinically relevant manner; nor does it make an appreciable difference, in clinical terms, in succinylcholine's duration of action.     

RETRACTED ARTICLE: Nicardipine enhances diaphragmatic fatigue

The effects of nicardipine, a calcium channel blocker, on diaphragmatic fatigue were studied in 20 anaesthetized, mechanically ventilated dogs divided into two groups: control group (Group C, n = 10) and nicardipine group (Group N, n -10). Diaphragmatic fatigue was induced by intermittent supramaximal electric stimulation to bilateral phrenic nerves at a frequency of 20 Hz for 30 min. In Group N, 5 μg · kg^?1· min^?1 nicardipine iv was infused continuously during this fatigueproducing period. Transdiaphragmatic pressure (Pdi) produced by electrical stimulation (10–100 Hz) of the phrenic nerves was used as an index of diaphragmatic contractility. After a fatigueproducing period, the Pdi in both groups decreased at low frequency (10–30 Hz) stimulation compared with pre-fatigue values (P < 0.05), whereas no change in Pdi was observed at high-frequency (50–100 Hz) stimulation. The decrease of Pdi at low-frequency stimulation was larger in Group N (P < 0.05). The integrated diaphragmatic electric activity (Edi) in both groups did not change at any frequency of stimulation throughout the experiment. We conclude that nicardipine enhances diaphragmatic fatigue.     

RETRACTED ARTICLE: Contractility of fatigued diaphragm is improved by dobutamine

The effects of dobutamine (DOB) on diaphragmatic fatigue were examined in 20 anaesthetized, mechanically ventilated dogs. Animals were divided into two groups: the DOB group (n = 10) and the control group (n = 10). Diaphragmatic fatigue was induced by intermittent supramaximal electric stimulation applied to bilateral phrenic nerves at a frequency of 20 Hz for 30 min. Diaphragmatic contractility was assessed with transdiaphragmatic pressure (Pdi). After diaphragmatic fatigue, Pdi decreased at low-frequency (20 Hz) stimulation (P < 0.05), whereas the decrease was minimal at high-frequency (100 Hz) stimulation. In the DOB group, after producing fatigue, the continuous administration of 10 μg · kg^?1 · min^?1 dobutamine iv for 30 min produced an increased Pdi at both frequencies of stimulation (P < 0.05). The Pdi returned to pre-fatigue values after cessation of dobutamine administration. In the control group, the speed of recovery from fatigue was much slower at low-frequency stimulation. The integrated diaphragmatic electric activity (Edi) in the two groups did not change throughout the experiment at any frequency of stimulation. We conclude that dobutamine improves contractility in fatigued diaphragm.     

Response to single twitch or single burst stimulation of the ulnar nerve as predictive guide for intubating conditions

Disappearance of response to single twitch stimulation (STS) or train-of-four stimulation (TOF) of the ulnar nerve is insufficient as predictive guide for intubating conditions during onset of non-depolarizing neuromuscular block. Double burst stimulation (DBS) appears to be a more reliable indicator of the optimal time for intubation. In the present study, the disappearance of tactile detectable response to 0.1 Hz single twitch stimulation (STS) of the ulnar nerve was compared with disappearance of response to 0.1 Hz single burst stimulation (three stimuli at 50 Hz=SBS) as predictor for optimal intubating conditions during onset of block induced by 0.08 mg . kg^-1 of vecuronium in 100 patients under light general anaesthesia where thiopentone was used as the sole anaesthetic. Intubation was performed immediately after disappearance of the twitch response. Likewise 0.05 Hz STS and 0.05 Hz SBS stimulation were compared under identical circumstances in another 100 patients. Intubating conditions were unacceptable in 10%, 14%, 8% and 10% of the patients in the 0.1 Hz STS, 0.1 Hz SBS, 0.05 Hz STS and 0.05 Hz SBS groups, respectively. There were no significant differences between the groups. In conclusion, neither absence of response to STS stimulation nor absence of response to SBS stimulation of the ulnar nerve at either 0.1 Hz or 0.05 Hz frequency does guarantee acceptable intubating conditions during onset of neuromuscular block induced by vecuronium 0.08 mg . kg^-1 when thiopentone is used as the sole anaesthetic.     

RETRACTED ARTICLE: Amrinone improves contractility of fatigued diaphragm in dogs

The effects of amrinone, a bipyridine derivative, on diaphragmatic contractility and fatigue were examined in 36 anaesthetized, mechanically ventilated dogs divided into four groups. In Group Ia (n = 8), dogs without diaphragmatic fatigue were given a bolus injection (0.75 mg · kg^?1) followed by continuous infusion (10 μg · kg^?1 · min^?1) of amrinone iv. In Group Ib (n = 8), animals without fatigue received infusion only of maintenance fluid. In Group IIa (n = 10) and Group IIb (n = 10), diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. After producing fatigue, amrinone (0.75 mg · kg^?1 loading dose plus 10 μg · kg^?1 · min^?1 maintenance dose) iv were administered in Group IIa. Only maintenance fluids were administered in Group IIb during this period. Diaphragmatic contractility was assessed in each group by measuring transdiaphragmatic pressure (Pdi). Compared with Group Ib, Pdi at any stimuli in Group Ia did not differ. After producing fatigue, in Group IIa and Group IIb, Pdi decreased at low-frequency (10–30 Hz) stimulation (P < 0.05), whereas no change in Pdi was observed at high-frequency (50–100 Hz) stimulation. In Group IIa, Pdi to each stimulus increased during amrinone infusion compared with Group IIb (P < 0.05). In Group IIb, the speed of recovery from fatigue was relatively slower at low-frequency stimulation. The integrated diaphragmatic electric activity (Edi) did not change throughout the experiment. These results indicate that amrinone improves contractility in the fatigued diaphragm.     

Dose-response characteristics of midazolam for reducing diaphragmatic contractility

A sedative dose of midazolam decreases contractility of the diaphragm, but no data are available concerning the relationship between dose and diaphragmatic contractility. We studied the dose-response characteristics of midazolam for reducing the diaphragmatic contractility in dogs. Animals were divided into three groups of eight each: Group 1 received no study drug, Group 2 was infused with a sedative dose of midazolam (0.1 mg/kg initial dose plus 0.1 mg x kg(-1) x h(-1) maintenance dose), and Group 3 was infused with an anesthetic dose of midazolam (0.1 mg/kg initial dose plus 0.5 mg x kg(-1) x h(-1) maintenance dose). We assessed the diaphragmatic contractility by transdiaphragmatic pressure (Pdi). With an infusion of midazolam in Groups 2 and 3, Pdi at low-frequency (20 Hz) and high-frequency (100 Hz) stimulation decreased from the baseline values (P < 0.05), and the integrated electrical activity of diaphragm (Edi) at 100-Hz stimulation decreased from the baseline values, whereas Edi at 20-Hz stimulation did not change. Compared with Group 1, Pdi and Edi for each stimulus decreased during midazolam infusion in Groups 2 and 3 (P < 0.05). The decrease in Pdi and Edi was more in Group 3 than in Group 2 (P < 0.05). We conclude that midazolam decreases, in a dose-dependent manner, contractility of the diaphragm in dogs.     

Dobutamine increases diaphragmatic contractility in dogs

The effects of dobutamine on diaphragmatic contractility were studied in 24 dogs anaesthetized with secobarbital and receiving mechanical lung ventilation. The phrenic nerves were stimulated supramaximally for two seconds with electrodes placed around the fifth and sixth cervical roots when the airway was closed at the level of FRC. The stimulating frequency ranged from 10 to 100 Hz. Transdiaphragmatic pressure gradient (Pdi) generated by the electrophrenic stimulation was used as an index of diaphragmatic contractility. The electrical activity of the diaphragm during the stimulation (Edi) was also measured with needle electrodes inserted in the right hemidiaphragm percutaneously. During an infusion of dobutamine (10 micrograms.kg-1.min-1 for 20 min), Pdi increased by 15 +/- 2.1% of control value at 20 Hz stimulation (P less than 0.01), and by 13 +/- 1.2% at 100 Hz stimulation (P less than 0.01). The Edi was not altered by dobutamine infusion. This enhancement of Pdi by dobutamine was abolished by simultaneous infusion of nicardipine, a Ca-channel blocker, but was not affected by prostaglandin E1. These results suggest that dobutamine has a stimulating effect on canine diaphragmatic contraction, and this action may be related to the increased inward movement of extracellular calcium.     

Isoflurane compared with nitrous oxide anaesthesia for intraoperative monitoring of somatosensory-evoked potentials

Intraoperative monitoring of somatosensoryevoked potentials is a routine procedure. To determine the depressant effect of nitrous oxide relative to isoflurane, the authors recorded the scalp, cervical and brachial plexusevoked responses to stimulation of the median nerve under different anaesthetic conditions. Eight subjects, age 35 ± 6 (SD) yr, weight 68 ± 12 kg, were studied. Following recording of awake control responses, anaesthesia was induced with thiopentone 5 mg· kg^{? 1} and fentanyl 3 μg· kg^{? 1} and was followed by succinylcholine 1 mg· kg^{? 1}. During normocapnia and normothermia, and with a maintenance infusion of fentanyl 3 μg · kg^{? 1}· hr^{? 1}, evoked potential recording was repeated under three different anaesthetic conditions; 0.6 MAC nitrous oxide, 0.6 MAC nitrous oxide ± 0.6 MAC isoflurane, and 0.6 MAC isoflurane. Among the anaesthetic conditions, the combination of nitrous oxide-isoflurane had the most depressant effect on the cortical amplitude (67 ± 4% reduction, P < 0.05). Nitrous oxide decreased the cortical amplitude more than an equipotent dose of isoflurane (60 ± 4% vs 48 ± 7%, P < 0.05). The latency was unchanged by nitrous oxide, but increased slightly by isoflurane and isofluranenitrous oxide anaesthesia (1.0 and 0.9 msec respectively, P < 0.05). We conclude that somatosensory-evoked potential monitoring is feasible both during nitrous oxide anaesthesia and isoflurane anaesthesia, but the cortical amplitude is better preserved during 0.6 MAC of isoflurane alone relative to 0.6 MAC of nitrous oxide alone. The depressant effect is maximal during nitrous oxideisoflurane anaesthesia but less than the predicted additive effect.     

Spontaneous breathing with the use of a laryngeal mask airway in children: comparison of sevoflurane and isoflurane

We compared respiratory parameters during anaesthesia with sevoflurane and isoflurane through a laryngeal mask airway (LMA). Children were anaesthetized with O₂ and air with 2.3% (1MAC) sevoflurane ( n =20) or 1.5% (1MAC) isoflurane ( n =20). After insertion of LMA, patients were allowed to breathe spontaneously and respiratory rate (RR) and P ECO2 were measured (presurgery state). After the measurement, anaesthetic concentration was increased to 1.3 MAC (3.0% sevoflurane or 2.0% isoflurane) and surgical stimulation was added. Fifteen min after incision, the measurements were again performed (during surgery). In the sevoflurane group, mean RR and P ECO2 were 32 breaths.min⁻¹, and 6.0 kPa (45 mmHg) respectively, before surgery, and 35 breaths.min⁻¹ and 7.0 kPa (52 mmHg) during surgery. In the isoflurane group, mean RR and P ECO2 were 32 breaths.min⁻¹ and 6.1 kPa (46 mmHg) respectively, before surgery, and 37 breaths.min⁻¹ and 6.7 kPa (52 mmHg) during surgery. There were no statistical differences between the two anaesthetic groups. Clinical respiratory and cardiovascular parameters during spontaneous breathing with LMA in children are similar during sevoflurane and isoflurane anaesthesia.     

The effects of enflurane,isoflurane, and intravenous anesthetics on rat diaphragmatic function and fatigability

We examined the effect of isoflurane, enflurane, midazolam, ketamine, propofol, and thiopental on diaphragmatic functions under unfatigued and fatigued conditions in 228 rat isolated muscle strips. Diaphragmatic twitch characteristics and tetanic contractions were measured before and after muscle fatigue, which was induced by repetitive tetanic contraction with or without exposure to one of the anesthetics at clinically relevant plasma concentrations, and at 10 and 100 times this concentration, or at 1, 2, and 3 minimum alveolar anesthetic concentration (MAC). Isoflurane, midazolam, ketamine, propofol, and thiopental did not induce a direct inotropic or lusitropic effect under unfatigued and fatigued conditions. Enflurane did not change contraction or relaxation in fresh isolated diaphragm, but enflurane at 2-3 MAC enhanced diaphragmatic fatigability itself and fatigue-induced impairment of twitch characteristics and tetanic tensions. These effects were greater at 3 MAC than at 2 MAC. Our findings suggest that the reduction of diaphragm function previously reported in in vivo experiments using propofol, midazolam, and isoflurane is not related to a direct effect on intrinsic diaphragmatic contractility. Our results also indicate that large concentrations of enflurane may impair the diaphragmatic function at sites other than excitation-contraction coupling. IMPLICATIONS: Enflurane did not change contraction or relaxation in fresh isolated rat diaphragm, but enhanced diaphragmatic fatigability itself and fatigue-induced impairment of twitch characteristics and tetanic tensions. Isoflurane, midazolam, ketamine, propofol, and thiopental had no direct effects on diaphragmatic functions under unfatigued and fatigued conditions. Isoflurane and these i.v. anesthetics may be advantageous over enflurane to anesthetize and/or sedate patients who are predisposed to diaphragmatic fatigue.     

The dose-range effects of propofol on the contractility of fatigued diaphragm in dogs.

Diaphragmatic fatigue may contribute to the development of respiratory failure. We studied the dose-range effects of propofol on the contractility of fatigued diaphragm in dogs. Animals were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation for 30 min. Immediately after the end of a fatigue-producing period, Group 1 received no study drug; Group 2 was infused with small-dose propofol (0.1 mg/kg initial dose plus 1.5 mg x kg(-1) x h(-1) maintenance dose); Group 3 was infused with large-dose propofol (0.1 mg/kg initial dose plus 6.0 mg x kg(-1) x h(-1) maintenance dose). We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After the fatigue-producing period, in each group, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, with an infusion of propofol, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05). Compared with Group 1, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05) during propofol administration in Groups 2 and 3. The decrease in Pdi was more in Group 3 than in Group 2 (P < 0.05). We conclude that propofol decreases the contractility of fatigued canine diaphragm in a dose-related fashion. IMPLICATIONS: Propofol is a widely used IV anesthetic for the induction and maintenance of general anesthesia and sedation. It decreases, in a dose-related fashion, the contractility of fatigued diaphragm in dogs.     

MAC-AWAKE OF ISOFLURANE, ENFLURANE AND HALOTHANE EVALUATED BY SLOW AND FAST ALVEOLAR WASHOUT

End-tidal anaesthetic concentrations at first eye opening inresponse to a verbal command during recovery from anaesthesia(MAC-awake), were measured for isoflurane (n = 16), enflurane(n = 16) and halothane (n = 14). MAC-awake was measured duringeither slow or fast alveolar washout. Slow washout was obtainedby decreasing anaesthetic concentrations in predetermined stepsof 15min, assuming equilibration between brain and alveolarpartial pressures. Fast alveolar washout was obtained by discontinuationof the inhalation anaesthetic, which had been maintained at1 MAC for at least 15 min. Mean MAC-awake obtained with slowalveolar washout was similar for isoflurane (0.25 (SD 0.03)MAC), and enflurane (0.27 (0.04) MAC) and significantly greaterthan values obtained by fast alveolar washout (isoflurane: 0.19(0.03) MAC; enflurane: 0.20 (0.03) MAC). The MAC-awake of isofluraneand enflurane was significantly less than that of halothane,which was 0.59 (0.10) MAC as evaluated by the slow and 0.50(0.05) MAC as evaluated by the fast alveolar washout method.Recovery time from anaesthesia with fast alveolar washout was8.8 (4.0) min for halothane, which was not different from isoflurane(15 (2.5) min), but significantly shorter than for enflurane(22 (10) min), reflecting differences in the anaesthetic concentrationgradient between MAC and MAC-awake values. These data do notsupport the hypothesis of a uniform ratio between MAC and MAC-awakevalues.