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Effects of controlled hypotension with sevoflurane anaesthesia on hepatic function of surgical patients

Fukusaki, M.; Miyako, M.; Hara, T.; Maekawa, T.; Yamaguchi, K.; Sumikawa, K.*

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European Journal of Anaesthesiology: February 1999 - Volume 16 - Issue 2 - p 111-116



Controlled hypotension is a technique that has been shown to reduce operative blood loss and homologous transfusion requirements during certain surgical procedures [1,2]. Intravenous drugs are usually used to achieve controlled hypotension with inhalation anaesthesia. Induced hypotension using higher inspired concentrations of inhaled anaesthetics alone may cause myocardial depression resulting in reduced organ perfusion and possible hypoxia.

Halothane has been reported to cause a dose-dependent depression in cardiac output [13] and to reduce hepatic blood flow more than isoflurane does in dogs [4] and humans [5]. Lam et al.[6] studied 13 patients in whom isoflurane was administered to achieve a mean arterial blood pressure of 40 mmHg and noted a small decrease in cardiac output. Isoflurane has been shown to increase hepatic blood flow at both one and two times minimum alveolar concentration (MAC) in contrast with halothane [4]. The cardiovascular [7] and hepatic [8] effects of sevoflurane are similar to those of isoflurane.

Controlled hypotension with trimethaphan and halothane causes a significant decrease in hepatic blood flow, while controlled hypotension with nitroglycerin or prostaglandin E1 maintains hepatic blood flow and hepatic function in dogs [9].

There are few studies that have evaluated hepatic function during controlled hypotension during sevoflurane anaesthesia.

This study examines the effect of controlled hypotension induced with trimethaphan (TMP), nitroglycerin (TNG) or prostaglandin E1 (PGE1) during sevoflurane anaesthesia on hepatic function in patients undergoing spinal fusion surgery.


Twenty-eight ASA physical status I or II patients with no pre-existing hypertension, ischaemic heart disease, cerebral infarction or hepatic disease, aged 26-58 years and weighing 57-76 kg, who were scheduled for spinal fusion surgery were studied. The protocol was approved by the hospital's institutional human investigation committee, and written informed consent was obtained from each patient.

Atropine sulphate 0.5 mg and hydroxyzine 1 mg kg−1 was given intramuscularly 1 h before the scheduled time of surgery. Anaesthesia was induced with intravenous thiamylal 4-5 mg kg−1 and fentanyl 2 μg kg−1, and maintained with 60% nitrous oxide in oxygen supplemented with 0.7 MAC end-tidal sevoflurane concentrations using a circle system with 5 L min−1 total flow. Tracheal intubation was facilitated with intravenous vecuronium 0.1 mg kg−1. Intravenous fentanyl 1-2 μg kg−1 and vecuronium 0.05 mg kg−1 were injected during surgery as required. Ventilation was controlled to maintain end-tidal CO2 tension at 4.5-5 kPa (Nellcor N-1000, Nellcor CMI, Kyoto, Japan). A radial artery catheter was inserted for continuous monitoring of arterial blood pressure and for obtaining blood samples. Lactated Ringer's solution containing 5% glucose was infused at 15 mL kg−1 before surgery over a 3- to 4-h period to prevent dehydration and hypoglycaemia. The infusion was continued at a rate of 8 mL kg−1 h−1 during surgery. Additional solution was infused at three times the amount of blood loss. Rectal temperature was maintained between 36°C and 37°C using a circulating water blanket and by adjusting room temperature.

Patients were divided randomly into three groups. Group A received controlled hypotension induced with TMP, group B received controlled hypotension induced with TNG and group C received controlled hypotension induced with PGE1. Mean arterial blood pressure was maintained at approximately 60 mmHg for approximately 90 min during controlled hypotension.

Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutylate), an index of hepatic cellular function, serum glutamate oxaloacetic transaminase (SGOT), serum glutamate pyruvate transminase (SGPT) and serum lactic dehydrogenase (LDH). Arterial blood gas and blood glucose were also measured.

AKBR was measured by the method of enzymatic analysis (enzyme immunoassay kit; Ketrex, Sanwakagaku, Nagoya, Japan). Arterial blood gas was analysed using a blood gas analyser (ABL-4; Radiometer, Copenhagen, Denmark). Blood glucose, SGOT, SGPT and LDH were measured by an automated analyser (Automatic analyser 736-20; Hitachi Corp., Tokyo, Japan). Measurement of AKBR was made before hypotension (T1), 60 min after starting hypotension (T2), 90 min after starting hypotension (T3) and 60 min after recovery from hypotension (T4). Measurements of SGOT, SGPT and LDH were made before surgery and on the third post-operative day.

The data were expressed as mean ± SD. Data were analysed using the Stat-View statistical program. Two-way repeated measures analysis of variance and Scheffe's test were performed for analysis of AKBR, haemodynamic data, blood gases and metabolic data. Student's t-test and one-way analysis of variance were used for analysis of the other data. A P-value less than 0.05 was considered statistically significant.


The three groups were similar with respect to gender, age, weight, operative time, hypotensive period, operative infusion volume, urinary output and operative blood loss (Table 1).

Table 1
Table 1:
Patient group characteristics

The changes in haemodynamic and metabolic variables are shown in Table 2. The mean doses of hypotensive drugs in this study were TMP 26.7 μg kg−1 min−1 (19.7-35.0 μg kg−1 min−1), TNG 4.7 μg kg−1 min−1 (1.8-9.2 μg kg−1 min−1) and in PGE1 0.142 μg kg−1 min−1 (0.080-0.250 μg kg−1 min−1).

Table 2
Table 2:
Changes in haemodynamic and metabolic parameters

Serum glucose concentrations were greater than 170 mg dL−1 in all groups. PaO2 values were more than 20 kPa in each group. There was no marked acidosis or alkalosis in any group. These values did not differ either within or between groups.

The mean values of AKBR at periods T2 to T4 were not significantly different from the control (T1) values in any group (Fig. 1). The changes in hepatic function are shown in Table 3. SGOT values measured on the third post-operative day were significantly greater in groups A and B, with no change in group C. Their values were within the normal range in all groups. SGPT values measured on the third post-operative day showed no change and were within the normal range in all groups. LDH values measured on the third post-operative day showed significant increases in groups A and C, with no change in group B. Their values were within the normal range in all groups. SGOT, SGPT and LDH values measured on the seventh and 14th post-operative days were within the normal range in all groups.

Fig. 1
Fig. 1:
Time course of changes in AKBR in group A, group B and group C (mean ± SEM,n = 10 in group A and group B and n = 8 in group C for each point). In group A, the value of AKBR at T1 was 1.11 ± 0.11 and showed no change at T2 (1.07 ± 0.22), T3 (1.16 ± 0.36) and T4 (2.02 ± 0.47). In group B, the value of AKBR at T1 was 1.12 ± 0.17 and showed no change at T2 (1.14 ± 0.18), T3 (1.32 ± 0.31) and T4 (1.55 ± 0.39). In group C, the value of AKBR at T1 was 1.45 ± 0.21 and showed no change at T2 (1.18 ± 0.11), T3 (1.26 ± 0.16) and T4 (1.39 ± 0.27). AKBR, arterial ketone body ratio; T1, before hypotension; T2, 60 min after starting hypotension; T3, 90 min after starting hypotension; T4, 60 min after recovery from hypotension. Normal range of AKBR >0.70.
Table 3
Table 3:
Changes in hepatic function


Hepatic blood flow has been reported to be closely related to cardiac index during sodium nitroprusside-induced hypotension [10]. Cardiac output is the main factor in controlling liver circulation. Malan et al.[7] showed that, although sevoflurane significantly decreased mean arterial blood pressure and cardiac out-put at 1.0 and 1.5 MAC in healthy volunteers, the changes in systemic haemodynamics were well tolerated. Sevoflurane has been studied with respect to its influence on hepatic perfusion in animals [11-13] and humans [14]. Conzen et al.[11] demonstrated that sevoflurane and isoflurane maintained total liver blood flow at an anaesthetic concentration that reduced mean arterial pressure to 70 mmHg, but decreased total liver flow when mean arterial pressure was reduced to 50 mmHg in rats. Fujita et al.[12] reported that 1.5 MAC of sevoflurane reduced portal blood flow and oxygen delivery more than 1.5 MAC of isoflurane. It did not reduce hepatic oxygen consumption as much as 1.5 MAC of halothane, and the hepatic oxygen supply/uptake ratio was less with sevoflurane than with halothane or isoflurane in a beagle dog model. These results suggest that, if hepatic arterial blood flow is compromised, there may be a smaller margin of safety against hypoxia with sevoflurane compared with halothane or isoflurane. It has been reported that 2 MAC of sevoflurane and isoflurane have a more favourable effect on liver circulation than halothane in adult patients using the indocyanine green clearance method as an index of hepatic circulation [14]. However, Eger et al.[15] reported that sevoflurane (8 h of 1.25 MAC concentration) using a standard circle absorber anaesthetic system at 2 L min−1 caused small post-anaesthetic increases in aminotransferase, suggesting mild, transient hepatic injury.

In the present study, sevoflurane at 0.7 MAC concentration with 60% N2O using a standard circle system at 5 L min−1 produced only minimal haemodynamic changes and did not cause hepatic cellular damage.

Hepatic venous O2 saturation, indocyanine green clearance and AKBR can be used as indices of hepatic circulation in humans. In this study, we measured plasma AKBR as a real-time index for ischaemic hepatic cellular damage, as AKBR is the least invasive of these methods. Fukusaki et al.[16,17] studied the combined effects of controlled hypotension and haemodilution on human hepatic function using AKBR. AKBR reflects the hepatic energy state [18]. Tanaka et al.[19] showed that AKBR correlated closely with ketone body ratio in hepatic tissue, which reflected the mitochondrial ratio of NAD+ to NADH and was related to the rate of mitochondrial oxidative phosphorylation. Thus, a decrease in AKBR (less than 0.70) would show that the damage to the hepatic mitochondrial energy process was caused by cellular factors. Hypoxia, hypoglycaemia and shock have also been reported to decrease AKBR [20], although in this study, Pao2 and glucose concentrations were maintained at levels greater than 25 kPa and 170 mgdL−1 respectively.

In the present study, AKBR did not change during TMP-, TNG- or PGE1-induced hypotension under sevoflurane anaesthesia. SGOT and LDH showed significant increases after TMP- and TNG-induced hypotension, although they remained within the normal range. The results indicate that controlled hypotension induced with TMP or TNG under sevoflurane anaesthesia does not impair hepatic function. TMP-induced hypotension with halothane anaesthesia produces significant decreases in cardiac output [21], and its profound hypotension causes ischaemic hepatic injury [22]. Wildsmith et al.[23] demonstrated that the blood lactate concentration did not increase during TMP-induced hypotension and suggested that the hepatic lactate clearance was preserved because hepatic blood flow did not fall. It seems that the hepatic O2 supply/uptake ratio might be less with TMP under sevoflurane anaesthesia. This study suggests that sevoflurane anaesthesia has a protective role decreasing oxygen demand in the liver. TNG-induced hypotension produces a decrease in cardiac output because TNG dilates capacitance vessels predominantly compared with resistance vessels [24]. Hoka et al.[25] reported that controlled hypotension induced with TNG maintained splanchnic blood flow because it did not cause blood flow redistribution from the splanchnic to extrasplanchnic vascular beds. Hepatic blood flow should have been preserved during TNG-induced hypotension under sevoflurane anaesthesia because cardiac output was maintained by ensuring sufficient preload with blood flow not being redistributed to the extrasplanchnic circulation. PGE1 has been reported to protect the hepatic cells, by a stabilizing effect on celullar membranes [26]. Hasegawa et al.[27] showed that PGE1-induced hypotension during isoflurane or sevoflurane anaesthesia for neurosurgery had little effect on post-operative liver function.

We conclude that controlled hypotension induced with TMP, TNG or PGE1 under sevoflurane anaesthesia is not associated with hepatic cellular damage in surgical patients.


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ANAESTHETIC TECHNIQUES, hypotension, controlled; PHARMACOLOGY, trimethaphan, nitroglycerin, prostaglandin E1; ORGAN PRESERVATION, liver; ANAESTHETICS, volatile, sevoflurane

© 1999 European Academy of Anaesthesiology