Department of Anaesthesiology, University of Tsukuba Institute of Clinical Medicine, 2-1-1 Amakubo, Tsukuba City, Ibaraki, Japan*Corresponding author
Accepted for publication: December 4, 2000
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Abstract |
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Br J Anaesth 2001; 86: 87981
Keywords: muscle skeletal, diaphragm; anaesthetics i.v., midazolam; anaesthetics i.v., propofol
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Introduction |
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Methods and results |
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Dogs were randomly divided into three groups of 10. After measuring baseline values of Pdi, Edi-cru, Edi-cost and haemodynamic variables, including heart rate and mean arterial pressure (MAP), in each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation applied for 30 min at a frequency of 20 Hz, an entire cycle of 4 s and a duty cycle of 0.5 (i.e. low-frequency fatigue).4 After the fatigue-inducing period, group II was given a bolus injection of propofol 0.1 mg kg1 followed by a continuous infusion (1.5 mg kg1 h1) i.v. with an electrical infusion pump for 60 min; group III received i.v. midazolam (0.1 mg kg1 loading dose plus 0.1 mg kg1 h1 maintenance dose) continuously with an infusion pump for 60 min. After administration of the study drug, Pdi, Edi-cru, Edi-cost and haemodynamic variables were measured. The doses used in the current study were based on the observation that a subhypnotic dose (1.5 mg kg1 h1) of propofol and a sedative dose (0.1 mg kg1 h1) of midazolam were widely used for equivalent sedation.3 5 In group I, only maintenance fluids were administered, and the same measurements were performed. The changes in Edi-cru and Edi-cost (%Edi-cru and %Edi-cost, respectively) from baseline were measured. At the end of the experiment, animals were killed with an overdose of pentobarbital.
Values are expressed as mean (SD). Statistical analysis was performed by ANOVA with Bonferroni correction for multiple comparison and Students t-test, as appropriate. P values of <0.05 were considered significant.
No differences in baseline variables were observed among the groups. In groups II and III, heart rate and MAP decreased below baseline (P<0.05) during administration of the study drug. After the fatigue-inducing period, Pdi at low-frequency (20 Hz) stimulation was lower than baseline (P<0.05) and Pdi at high-frequency (100-Hz) stimulation did not change in each group. In group II, Pdi at 20 Hz stimulation was lower than fatigued values (P<0.05); Pdi at 100 Hz stimulation did not change. In group III, Pdi at both stimuli was lower than fatigued values (P<0.05). The decrease in Pdi was greater in group III than in group II (P<0.05). In group III, both Edi-cru and Edi-cost at 100 Hz stimulation during midazolam administration were less than baseline values (P<0.05) (Table 1).
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Comment |
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In a preliminary study, we examined the effects of propofol on contractility in the non-fatigued diaphragm. With an infusion of propofol at a subhypnotic dose (1.5 mg kg1 h1), Pdi at 20 Hz stimulation was lower than baseline; Pdi at 100 Hz stimulation and Edi did not change.3 In group II, Pdi at 20 Hz stimulation was lower than fatigued values (P<0.05); Pdi at 100 Hz stimulation and Edi did not change. These results suggest that propofol may decrease the contractility of both fatigued and non-fatigued diaphragms. The exact mechanism by which propofol decreases the contractility of the diaphragm is unknown. However, these phenomena during propofol administration are similar to the characteristics of low-frequency fatigue, which is also related to impaired coupling of excitation and contraction.4 8 Therefore, it is possible that an inhibitory effect of propofol on diaphragmatic muscle function may be related to an impediment of excitationcontraction coupling.
In group III, midazolam reduced Pdi at both stimulation frequencies compared with fatigued values (P<0.05), and Edi-cru and Edi-cost at 100 Hz stimulation during midazolam administration were less than those obtained in the baseline period (P<0.05). The precise mechanism by which midazolam reduces the contractility of fatigued diaphragm with a reduction of electromyographic activity (as assessed by Edi) is not known. Selective loss of force at low-frequency stimulation is closely related to the impairment of excitationcontraction coupling,8 whereas selective loss of force and electromyographic activity at high-frequency stimulation indicates the failure of neuromuscular transmission.9 10 Therefore, reductions in Pdi at low- (20 Hz) and high-frequency (100 Hz) stimulation and in Edi at high-frequency (100-Hz) stimulation may result from impairment of excitationcontraction coupling and failure of neuromuscular transmission.
In conclusion, we have shown that midazolam, compared with propofol, reduces Pdi at both stimulation frequencies in fatigued diaphragm (P<0.05), suggesting that midazolam causes more contractile inhibition.
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References |
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