1Department of Anaesthesiology and Intensive Care, Hotel Dieu Hospital, Lyon, France. 2Department of Anaesthesiology and Intensive Care, Hotel Dieu Hospital, Lyon and Department of Research EA 18/96, Claude Bernard University, Lyon, France*Corresponding author
Accepted for publication: February 13, 2001
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Abstract |
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Br J Anaesth 2001; 86: 2803
Keywords: anaesthetics, volatile, desflurane; infection, bacteraemia; pig
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Introduction |
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As for other volatile anaesthetic agents, several factors affect the minimum alveolar concentration of desflurane (MACDES) in pigs, including age, body temperature, additional anaesthetic drugs, acidbase status, concentrations of carbon dioxide and brain electrolytes, type of supramaximal stimulus and haemodynamics.46
The pharmacokinetics of desflurane have been well characterized in humans and other animals,2 but no data are currently available on MACDES requirements in septic animals or patients. The aim of this study was to test whether sepsis can change MACDES requirements in an animal model of sepsis.
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Methods and results |
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MACDES was assessed in each pig as described previously,5 beginning with a 10% end-tidal concentration of desflurane. A haemostatic clamp was placed on the hind limb and moved cranially and caudally for 1 min. If no purposeful response was obtained, the desflurane expired concentration was decreased by 20%. Fifteen minutes were allowed to achieve equilibration and the stimulus was repeated. The end-tidal desflurane concentration was decreased further, step by step, until there was purposeful movement. The desflurane concentration was then increased by 0.3% steps, and after the equilibration period, the stimulus was repeated. The desflurane concentration midway between that allowing and that preventing movement was taken to be the MACDES. Once MACDES had been determined, haemodynamics, end-tidal carbon dioxide concentration and core temperature were recorded. Arterial blood samples were simultaneously collected for gas analysis and measurement of plasma lactate concentrations. Pigs were randomly allocated to two groups with carefully prepared opaque sealed envelopes. The saline group received a 1 h infusion of saline solution (1 ml kg1) and the sepsis group a 1 h i.v. infusion of live Pseudomonas aeruginosa. In keeping with previous studies,7 0.3 ml of bacteria (5x108 cfu ml1) were infused per 20 kg bodyweight per minute. In both groups, haemodynamic status and core temperature were assessed 30, 60, 120, 180, 240 and 300 min after infusion of bacteria or saline. Hydroxyethylstarch and epinephrine were used shortly after the infusion to maintain a pulmonary artery occlusion pressure (PAOP) between 8 and 15 mm Hg and a mean systemic arterial pressure (MAP) between 60 and 70 mm Hg.7 MACDES was assessed again 5 h after the end of the infusion. One physician assessed MAC before and after infusion and was not aware of the nature of the infusion or of haemodynamic status; another physician was enrolled to administer the infusion and to manage potential sepsis.
MACDES data are expressed as median (95% confidence intervals) and were compared using the MannWhitney test. Haemodynamic data were compared using the Friedman test. No statistically significant differences in MACDES were observed between the groups before saline and bacterial infusion: the median (95% confidence interval) MACDES before infusion was 9.7% (8.710.4%) in the saline group and 9.5% (8.610.3%) in the sepsis group (Figure 1). MACDES for the saline group was 9.2% (6.810.6%) after saline infusion and that for the sepsis group was 6.7% (4.710.4%) after bacterial infusion (P<0.05) (Figure 1). The mean pulmonary arterial pressure (MPAP) in the sepsis group was significantly (170%) higher 30 min after the end of perfusion, and then decreased gradually to a steady state with persistent pulmonary hypertension for the remainder of the study when compared with the saline group. Pulmonary vascular resistance had increased significantly (by 333%) in the sepsis group 30 min after the end of the bacterial infusion, then declined but remained significantly higher than that in the saline group (+96%). Heart rate increased continuously 1 h after the end of bacterial infusion (+18%) and increased by the end of the study (+23%). Cardiac output had significantly increased in the sepsis group (+23%) 1 h after the end of bacterial infusion and remained elevated until the end of the study (+60%).
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Comment |
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Many pathophysiological conditions can affect MACDES, including additional anaesthetic drugs, differences in core temperature, age, acidbase status, concentrations of electrolytes in cerebrospinal fluid, hypotension and prolonged anaesthesia.46 Premedication with i.m. ketamine and induction with propofol affect MACDES. Nevertheless, MACDES values in the two groups were not statistically different before infusion and were close to values reported by Eger and colleagues (10±0.94%).5 There were no statistically significant differences in core temperature between the groups, so the reduction in MACDES in the septic group cannot be explained by changes in temperature. Suspected occult tissue hypoxia associated with sepsis could have produced metabolic acidosis, indicating anaerobic metabolism. This phenomenon is likely to have contributed to the decreased anaesthetic requirement.9 In our study, there was no difference in arterial lactate concentrations or acidbase status. However, lactate is an unreliable indicator of tissue hypoxia in sepsis10 and, in our septic model, tissue hypoxia could have occurred without metabolic changes. Hypotension has been reported to decrease the MAC of volatile anaesthetic agents.6 However, in our study, because of epinephrine and hydroxyethylstarch/saline therapy, septic pigs remained normotensive. In the case of haemodynamic failure, MACDES is likely to be altered more, but this would differ from septic patients undergoing surgical procedures. Another possible explanation of the reduction in MACDES is cerebral electrolyte dysfunction;4 in this study we did not measure electrolyte concentrations in cerebrospinal fluid. Another potential cause of discrepancies in the reduction of MACDES is fluid and drug resuscitation. Hydroxyethylstarch and epinephrine were administered to mimic an anaesthetists method of sustaining arterial pressure. Steffey and Eger found that epinephrine had no effect on the MAC of halothane in dogs.11 Our results support the hypothesis that changes in anaesthetic requirement might be related, in part, to the use of hydroxyethylstarch. However, the influence of hydroxyethylstarch on MAC requirements has never been explored. Differences in MACDES can arise from the central nervous system dysfunction associated with sepsis. Encephalopathy, alterations in neurotransmitter levels, changes in receptor function and brain Ca2+ accumulation occur early during sepsis.1 Changes in regional blood flow and in the energy status of skeletal muscle appear during sepsis.12 Thus anaesthetic requirements could be reduced in these models and could possibly explain the lower MACDES in the septic group.1
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Acknowledgements |
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References |
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