Cardiovascular stability during inhalational anaesthesia in morbidly obese patients: which is better, sevoflurane or desflurane?

Editor—We read with interest the manuscript by De Baerdemaeker and colleagues1De Baerdemaeker LEC Struys MMRF. Jacobs S. et al.Optimization of desflurane administration in morbidly obese patients: a comparison with sevoflurane using an ‘inhalation bolus’ technique.Br J Anaesth. 2003; 91: 638-650Crossref PubMed Scopus (69) Google Scholar on the optimization of desflurane and sevoflurane administration in morbidly obese patients by using an inhalation bolus technique. The authors must be complimented for developing this interesting technique in the obese population; however, there are two points that deserve comment. We agree with the authors that using BIS-guided administration of the volatile anaesthetic can overcome the problem of under- or overdosing, as reported when the level of anaesthesia is titrated only on the value of MAC.2Song D Joshi GP White PF. Titration of volatile anesthetic using bispectral index facilitates recovery after ambulatory anesthesia.Anesthesiology. 1997; 87: 842-848Crossref PubMed Scopus (352) Google Scholar However, when giving the bolus of the volatile agent to patients in the sevoflurane group, the inspired concentration of the volatile anaesthetic was increased up to a value >4 MAC, while in patients anaesthetized with desflurane the inspired concentration was increased only up to 2.5 MAC.3Nickalls RWD Mapleson WW. Age‐related iso‐MAC charts for isoflurane, sevoflurane and desflurane in man.Br J Anaesth. 2003; 91: 170-174Crossref PubMed Scopus (255) Google Scholar As one of the main aims of the study was evaluation of the cardiovascular effects of the bolus technique when using these two volatile anaesthetics, the authors should have used equipotent boluses in the two groups, in order to minimize the risk of bias towards one of the two agents. Second, in the discussion, the authors state that haemodynamic stability was better in patients receiving desflurane than in those receiving sevoflurane, attributable to fewer, and shorter episodes of hypotension. This statement is based on the observation that the percentage time when the mean arterial blood pressure was <60 mm Hg was greater with sevoflurane than desflurane. However, it seems that the authors did not consider that clinically relevant hypotension (a decrease of mean arterial blood pressure >50 mm Hg) occurred less frequently in patients in the sevoflurane group (8 out of 25, 32%) than in patients anaesthetized with desflurane (16 out of 25, 64%) (Fisher's exact test: P=0.04). We agree that the incidence of clinically relevant hypotension was more related to patient position and releasing the pneumoperitoneum than to the administration of boluses of the volatile agents; nonetheless, it must be pointed out that the only systematic difference between the two groups was the volatile agent used to maintain general anaesthesia, which suggests that the haemodynamic effect may have been related to the drug used. If we combine these two observations and consider that the incidence of clinically relevant hypotension was much less frequent with sevoflurane despite the use of 50% larger boluses, it could be concluded from this investigation that the haemodynamic stability of morbidly obese patients is better with sevoflurane than desflurane. In conclusion, we do believe that the bolus technique described by De Baerdemaeker and colleagues is interesting and acceptable for use in morbidly obese patients; however, further properly designed studies should be advocated to evaluate better the haemodynamic profile of these two volatile anaesthetics in this patient population. A. Casati Editor—I would like to thank Dr Casati and Professor Torri for their comments and interest in our paper and for the opportunity to reply. I will address their points in turn. One of the limitations of giving an inhalation bolus is the technical limitation of the vaporizer. The maximum output of a vaporizer is 8% for sevoflurane and 18% for desflurane. In studying the cardiovascular stimulation associated with rapid increases in desflurane concentrations, Weiskopf and colleagues4Weiskopf RB Moore MA Eger II, EI et al.Rapid increase in desflurane concentration is associated with greater transient cardiovascular stimulation than with rapid increase in isoflurane concentration in humans.Anesthesiology. 1994; 80: 1035-1045Crossref PubMed Scopus (180) Google Scholar used a fresh gas flow of 10 litre min−1 and a delivered anaesthetic concentration of desflurane 18% in order to increase the alveolar concentration as rapidly as possible from 0.55 MAC to 1.66 MAC. The average time for these desflurane inhalation boluses was 66 s (sd 7 s). The cardiovascular and endocrine responses were dramatic. High inspiratory concentrations can cause cardiovascular instability and bronchospasm. Because of a lack of data on the use of high inspiratory concentrations in morbidly obese patients, and thus for safety reasons, we limited the boluses of desflurane to 2.5 MAC (16%). We did not perform a prospective simulation of the bolus administration with commercially available programs that model uptake and distribution because the inhalation bolus can be given at any moment during surgery at various, unpredictable end-tidal concentrations. Simulation was in our opinion futile. Interestingly, we simulated post hoc an inhalation bolus for five ‘average’ patients in each group (115 kg and an alveolar ventilation of 7.44 litre min−1 for the sevoflurane group vs 116 kg and 7.56 litre min−1 in the desflurane group) with the gasman program written by James H. Philip (MED MAN Simulations, Inc., Chestnut Hill, MA, USA). After 15 min of our study protocol, the 30 s bolus resulted in a mean (sd) MAC of 0.84 (0.06) in the sevoflurane group and MAC 0.87 (0.02) in the desflurane group. To illustrate our findings, we performed some additional analysis of our original data. In our study, the 41 boluses in the sevoflurane group resulted in a mean maximal end-tidal concentration of 1.48 (0.33) MAC. The 34 boluses in the desflurane group resulted in a mean maximal end-tidal concentration of 1.20 (0.24) MAC (independent samples, t-test P<0.0001). Even though the inspiratory concentrations of the sevoflurane boluses were 50% larger then the desflurane boluses, the MAC difference was only 0.3. We agree with Dr Casati that these boluses did not result in an equipotent MAC, but this was not our objective. The inhalation bolus was used as a tool to control depth of hypnosis as rapidly as possible. The MAC concept refers to movement at incision, so it implies analgesia and not hypnosis. The MAC value of volatile anaesthetics does not predict the level of hypnosis during general anaesthesia. In this respect, sevoflurane performed better than desflurane. Our detailed analysis of the haemodynamic changes during these boluses showed no hypotension, nor hypertension, and both agents proved to be haemodynamically safe during bolus administration. In analysing the haemodynamics, we calculated the percentage of case time with a mean arterial pressure (MAP) <60 mm Hg. These percentages include periods with a MAP <50 mm Hg. We agree with Dr Casati that the frequency of these periods of MAP <50 mm Hg was higher in the desflurane group, but not the duration. The cumulative case time of MAP <50 mm Hg was 35 min (3.6% of total case time) in the 16 desflurane patients vs 112 min (6.4% of total case time) in the eight sevoflurane patients (Fisher's exact test, P=0.002). So I cannot agree with Dr Casati's statement that haemodynamic stability of morbidly obese patients is better with sevoflurane than desflurane, based on the observation of fewer episodes of MAP <50 mm Hg. These fewer periods simply lasted longer. Dr Casati pointed out that the only systematic difference between the two groups was the volatile agent, so the observed haemodynamic effect could be related to the agent used. Theoretically, sevoflurane should offer better haemodynamic stability than desflurane, but in this study protocol it did not. One could question if this is attributable to the investigated population or if the pharmacokinetics of volatile agents are different in morbidly obese patients. How can we explain this observation? Opioids reduce MAC and MACBAR, but with a ceiling effect at a MAC value equal to the MACawake of the volatile anaesthetic used. MACawake is barely influenced by the selected opioids.5Glass PSA Gan TJ Howeel S Ginsberg B. Drug interactions: volatile anesthetics and opioids.J Clin Anesth. 1997; 9: 18S-22sAbstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar Daniel and colleagues6Daniel M Weiskopf RB Noorani M Eger II., EI Fentanyl augments the blockade of the sympathetic response to incision (MACBAR) produced by desflurane and isoflurane: desflurane and isoflurane MACBAR without and with fentanyl.Anesthesiology. 1998; 88: 43-49Crossref PubMed Scopus (85) Google Scholar found that the MACBAR of desflurane combined with opioids is 0.9–1.05 with a ceiling effect 5 min after a bolus of fentanyl 3 μg kg−1. In their work on the effect of fentanyl on the MACBAR of sevoflurane, Katoh and colleagues7Katoh T Kobayshi S Suzuki A Iwamoto T Bito H Ikeda K. The effects of fentanyl on sevoflurane requirements for somatic and sympathetic responses to surgical incision.Anesthesiology. 1999; 90: 398-405Crossref PubMed Scopus (125) Google Scholar used the pharmacokinetics of Shafer and colleagues8Shafer Sl Varvel JR Aziz N Scott JC. Pharmacokinetics of fentanyl administered by computer‐controlled infusion pump.Anesthesiology. 1990; 73: 1091-1102Crossref PubMed Scopus (231) Google Scholar to calculate the fentanyl effect-site concentration of 3.5 ng ml−1 after the same bolus dose. Taking into account the equipotency ratio of 1.2 with remifentanil, this equals a remifentanil plasma concentration of 4.2 ng ml−1, a concentration that was reached in our desflurane group. Recently, Albertin and colleagues9Albertin A Casati A Bergonzi P Fana G Torri G. Effects of two target‐controlled concentrations (1 and 3 ng/ml) of remifentanil on MACBAR of sevoflurane.Anesthesiology. 2004; 100: 255-259Crossref PubMed Scopus (58) Google Scholar published the reduction in sevoflurane requirements needed for blunting sympathetic responses to incision during a target-controlled remifentanil infusion. A target-controlled infusion of remifentanil 1 ng ml−1 resulted in a 60% decrease in the MACBAR of sevoflurane (1.1 MAC), and a target-controlled infusion of 3 ng ml−1 produced a further 30% decrease of MACBAR (0.68 MAC). They excluded obese patients, but the Minto–Schnider model that was used is applicable in obese patients as shown by Egan and colleagues.10Egan TD Huizenga B Gupta SK et al.Remifentanil pharmacokinetics in obese versus lean patients.Anesthesiology. 1998; 89: 562-573Crossref PubMed Scopus (231) Google Scholar The mean (sd) MAC value for the sevoflurane group was 0.71 (0.22) and the mean (sd) MAC value for the desflurane group was 0.56 (0.15) (t-test for equality of means, P=0.006). In our opinion, this could explain the higher percentage of time when hypotension was observed in the sevoflurane group, especially when positioning the patient in reverse Trendelenburg and deflation of the pneumoperitoneum. Both groups started with a target-controlled infusion plasma target of 4 ng ml−1 and an FD of 1 MAC with a fresh gas flow of 6 litre min−1 during the initial 5 min. In the early stage of the procedure and when deflating the pneumoperitoneum, conditions of MACBAR were definitely met in the sevoflurane group, probably resulting in more hypotension. Or was it attributable to the more pronounced spinal effects of sevoflurane? Rampil and colleagues11Rampil IJ King BS. Volatile anesthetics depress spinal motor neurons.Anesthesiology. 1996; 85: 129-134Crossref PubMed Scopus (139) Google Scholar showed that desflurane, sevoflurane, enflurane and isoflurane depressed the excitability of spinal motor neurons in rats. The magnitude of depression is comparable at equipotent MAC concentrations of the investigated agents. Because MAC was higher in the sevoflurane group, the spinal effects could have been greater with this agent. In our paper,1De Baerdemaeker LEC Struys MMRF. Jacobs S. et al.Optimization of desflurane administration in morbidly obese patients: a comparison with sevoflurane using an ‘inhalation bolus’ technique.Br J Anaesth. 2003; 91: 638-650Crossref PubMed Scopus (69) Google Scholar one can see in Fig. 2a that peak plasma concentration tended to be higher in the desflurane group. Opioids reduce MAC. This is probably why MAC desflurane was lower than MAC sevoflurane attributable to more MAC reduction from remifentanil. The desflurane group was comparable with high-dose opioids with maximum MAC reduction at levels near MACawake. None of our patients reported awareness during anaesthesia. L De Baerdemaeker Gent, Belgium