1Department of Anesthesiology, Fukushima Medical University School of Medicine, Fukushima, Japan and 2Department of Anesthesiology, Toride Kyodo General Hospital, Ibaraki, Japan*Corresponding author: Department of Anesthesiology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima City, Fukushima, 9601295, Japan
Accepted for publication: January 31, 2001
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Abstract |
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Br J Anaesth 2001; 86: 81421
Keywords: monitoring, neuromuscular function; neuromuscular block; temperature, body; neuromuscular block, vecuronium; pharmacology, vecuronium
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Introduction |
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If the temperature over the adductor pollicis is decreased, recovery from neuromuscular block in this muscle is delayed.9 10 An infusion of amino acid-enriched solution may speed recovery from neuromuscular block because amino acids prevent hypothermia. However, no previous studies have investigated the effect of amino acids on neuromuscular block and temperature over the adductor pollicis muscle during general anaesthesia. In this study, we examined the recovery of post-tetanic count (PTC) and the train-of-four (TOF) response, and changes in rectal temperature or surface temperature and the adductor pollicis muscle, during a continuous infusion of amino acid enriched solution in anaesthetized patients receiving vecuronium compared with controls.
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Methods |
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Pre-medication consisting of atropine 0.01 mg kg1 and hydroxyzine 1.0 mg kg1 was given i.m. 30 min before induction of anaesthesia. On arriving at the operating theatre, two surface stimulating electrodes were positioned over the ulnar nerve at the wrist. A force displacement transducer was attached to the thumb of one arm.
Infusion of amino acids and monitoring of neuromuscular block
In each group, acetate Ringers solution was infused i.v. at a rate of 500 ml h1 via an 18-gauge catheter inserted into the cubital vein. In each group, anaesthesia was induced with propofol 2 mg kg1. After loss of the eyelash reflex, TOF stimuli were applied every 12 s using a nerve stimulator (Myotest DBS, DBS-000E, Biometer International, Odense, Denmark). Four square-wave twitch stimuli of 0.2 ms duration were applied at 2 Hz. The mechanical response of the adductor pollicis muscle was measured using a neuromuscular transmission analyser (Myograph 2000, Biometer International, Odense, Denmark). In each patient, TOF stimuli were delivered at 20, 30, 40, 50, and 60 mA. If a supramaximal response of the thumb was produced at 20, 30, 40, or 50 mA, the stimulating current for the patient was fixed at 50 mA. If the supramaximal response of the thumb could not be produced at 50 mA, the stimulating current for the patient was fixed at 60 mA. The height of the first response of the TOF was regarded as control twitch height (T0). The control value was determined 23 min after starting TOF stimuli. During this stabilization period, the patients lungs were ventilated using a facemask with oxygen 6 litre min1 and isoflurane 1% inspired concentration.
A continuous i.v. infusion of a mixture of 18 amino acids (AMIPAREN®, Otsuka Pharmaceutical Inc., Tokyo, Japan) (Table 1) was then started in the AA-PTC and AA-TOF groups at a rate of 100 ml h1, corresponding with 166 kJ h1 of energy, using a syringe pump (Terufusor, TE-312, Terumo Inc., Tokyo, Japan). The infusion rate was determined according to the AMIPAREN® data sheet. There after, vecuronium 0.1 mg kg1 was administered i.v. to facilitate tracheal intubation. In the C-PTC and C-TOF groups, the degree of neuromuscular block was monitored in the same manner as in the AA-PTC and AA-TOF groups and vecuronium 0.1 mg kg1 was injected to facilitate tracheal intubation. Normal saline was infused continuously at a rate of 100 ml h1 instead of the infusion of the amino acid enriched solution. All i.v. fluids were at room temperature. A warming mattress (Medi-Therm, MTA-4700, Gaymar Industries Inc., New York, NY, USA) had been laid on the operating bed, and the temperature of the warm water in the warming mattress was kept at 37°C. The monitored arm was covered with towels. The room temperature was 2728°C.
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In the AA-TOF and C-TOF groups, TOF stimuli were applied every 12 s at 50 or 60 mA. The times from vecuronium to the return of T1, T2, T3, and T4 (the first, second, third, and fourth response in TOF) were compared between the two groups. T1/T0 and T4/T1 were recorded every 10 min, and were also compared between the AA-TOF and C-TOF groups.
Measurement of rectal temperature and surface temperature over adductor pollicis muscle
About 5 min before induction of anaesthesia, a thermometer probe was inserted 1015 cm into the rectum and the rectal temperature was monitored on an anaesthesia monitoring system (Anesthesia System/3, AS/3, Datex-Ohmeda Division Instrumentarium Corp. Inc., Helsinki, Finland). A surface skin thermometer probe (Terumo-Finer, CTM-303, Terumo Inc., Tokyo, Japan) was positioned over the adductor pollicis muscle in each patient.
Control rectal temperature and temperature over the adductor pollicis muscle were recorded. From the beginning of the infusion of the amino acid enriched solution, the two temperatures were noted every 10 min. The rectal temperatures recorded in the AA-PTC and AA-TOF groups were compared with that evaluated in the C-PTC and C-TOF groups. Similarly, the temperature over the adductor pollicis muscle in the AA-PTC and AA-TOF groups was compared with that in the C-PTC and C-TOF groups every 10 min.
Anaesthetic management
In each group, anaesthesia was maintained with nitrous oxide 66% in oxygen and 0.5% end-tidal isoflurane. A bolus dose of fentanyl 2 µg kg1 was administered i.v. If the depth of anaesthesia was thought to be insufficient, a further bolus dose of fentanyl 2 µg kg1 was given. Ventilation was controlled to maintain normocapnia (PE'CO2 4.15.0 kPa). The anaesthetic concentrations and PE'CO2 were measured continuously using a multiple gas monitor (Capnomac Ultima, S-3103, Datex Inc., Helsinki, Finland).
Statistical analyses
All results are expressed as number or mean (SD). Patient characteristics were compared among the four groups using analysis of variance (ANOVA) and Scheffes multiple comparison. The times to return of PTC1 between the AA-PTC and C-PTC groups were compared using the unpaired t-test. Similarly, times to return of T1, T2, T3, or T4 were compared between the AA-TOF and C-TOF groups using the unpaired t-test. Comparison of time courses of recovery of PTC between the AA-PTC and C-PTC groups was made using KruskalWallis test followed by MannWhitney U-test with Bonferronis adjustment. The time courses of recovery of T1/T0 and T4/T1 were compared between the AA-TOF and C-TOF groups using ANOVA followed by unpaired t-test with Bonferronis adjustment. The comparison of the changes in rectal temperature between the AA-PTC and AA-TOF groups, and the C-PTC and C-TOF groups, and the comparison of the changes in the temperature over the adductor pollicis muscle between the AA-PTC and AA-TOF groups and the C-PTC and C-TOF groups were made using ANOVA followed by the unpaired t-test with Bonferronis adjustment. A P value <0.05 was considered statistically significant. Statistical analyses were performed using a statistical package (SYSTAT 8.0, SPSS Inc., Chicago, IL, USA) running on a personal computer.
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Results |
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Before induction of anaesthesia, the rectal temperature in the AA-PTC and AA-TOF groups and that in the C-PTC and C-TOF groups did not significantly differ (36.8 (0.3) versus 37.0 (0.6)°C, NS). Similarly, before induction of anaesthesia, the temperature over the adductor pollicis muscle in the AA-PTC and AA-TOF groups was comparable with that in the C-PTC and C-TOF groups (33.1 (1.3) vs 32.9 (1.1)°C, NS). Rectal temperature decreased by approximately 0.2 and 0.5°C respectively in patients receiving an amino acid infusion or controls during the study period of 120 min. Rectal temperature in patients receiving an amino acid infusion became stable about 80100 min after starting the administration of amino acid. In contrast, rectal temperature in patients in the control groups continued to decrease gradually during the study period. The peripheral temperature over the adductor pollicis muscle increased by about 2.7 and 2.0°C in patients receiving amino acids and in the control group respectively. The increases in the peripheral temperature in patients receiving amino acids and in the control group were rapid for the first 30 min, became stable within about 4060 min. The decrease in the rectal temperature was less and the increase in the surface temperature over the adductor pollicis muscle was greater in the AA-PTC and AA-TOF groups than in the C-PTC and C-TOF groups 50120 and 100120 min after the beginning of administration of amino acid enriched solution respectively (P<0.05) (Figs 4 and 5).
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Discussion |
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Amino acids are readily available energy substrates for skeletal muscle.15 Several studies have demonstrated amino acid-induced thermogenesis in patients during general anaesthesia.3 68 The infusion of amino acid enriched solution prevents hypothermia.48 It has been postulated that amino acid-induced heat production is mainly a result of the delivery of energy substrates to skeletal muscle.3 6 Approximately 75% of amino acid-induced thermogenesis during anaesthesia seems to be produced here.3 6
The amino acid-induced thermic effect is more apparent in patients under general anaesthesia than in awake subjects.6 11 The reason for this is unknown. It has been reported that most anaesthetic agents considerably reduced whole body oxidative metabolism and hence the production of heat.7 For example, volatile anaesthetics directly depress protein synthesis and induce hypothermia.6 Amino acid enriched solution may reverse the cooling effect of the volatile agents.
Mourier and colleagues2 reported that even when wrestlers were subjected to moderate energy restriction, branched-chain amino acid supplementation allowed maintenance of a high level of sports performance. Similarly, Nissen and colleagues1 demonstrated that the leucine metabolite, ß-hydroxy-ß-methylbutyrate, produced a significant increase in muscle strength. The amino acid-induced thermic effect may be related to this increase in muscle strength. The solution increased muscle strength may also prevent the hypothermia.
This study showed that the amino acid-induced effect on recovery of neuromuscular block had a very rapid onset. For example, the mean time from vecuronium injection to the return of PTC1 in the C-PTC group was 18.0 min, but in the AA-PTC group was only 13.3 min. Also, Selldén and Lindahl6 and Selldén and colleagues7 have reported that during general anaesthesia, the body temperature in patients who were given the amino acid enriched solution becomes significantly higher than that in patients who did not receive it within 20 min.
In previous studies,6 8 rectal temperature decreased by approximately 0.5°C and 1.01.5°C respectively during general anaesthesia in patients receiving an amino acid infusion or controls. In contrast, in this study, the maximum decreases in the rectal temperature were only 0.2 and 0.5°C respectively. We are not able to explain the reason for this difference. However, El-Gamal and colleagues12 reported that an operating room temperature around 26°C is effective in preventing a decrease in core temperature during general anaesthesia. In this study, the operating room temperature was 2728°C, in contrast with 2023°C in the previous studies.6 8
It has been noted that if the temperature over the adductor pollicis muscle is less than 32°C, recovery of neuromuscular block is delayed.9 10 Hypothermia is associated with a decrease in acetylcholine release.9 10 The present results may be because of in part the prevention of hypothermia at the adductor pollicis muscle. But in two patients in the AA-PTC and AA-TOF groups and four in the C-PTC and C-TOF groups, when vecuronium was given, the peripheral temperature over the adductor pollicis muscle was less than 32°C. Accordingly, in these patients, recovery of neuromuscular block might have been delayed. However, by 10 min after vecuronium, the peripheral temperature over the adductor pollicis muscle had increased to more than 32°C in these patients.
In this study, the peripheral temperature over the adductor pollicis muscle increased by about 2.7 and 2.0°C in patients receiving amino acids and in the control group respectively. In all patients, the peripheral temperature became stable within 4060 min. These results were comparable with the findings of Sessler and colleagues,13 although in their study, the increase in the surface skin temperature over the hand was greater than 4°C. They noted that the increase in the surface skin temperature was a result of the redistribution of heat from the warm central compartment to cooler peripheral tissues.
Neuromuscular monitoring was started after loss of the eyelid reflex, but 1% isoflurane was then used for maintenance of anaesthesia for the 2 or 3 min before control readings of the TOF were taken. The use of isoflurane might have affected the neuromuscular response. However, it has been reported that 10 min exposure to isoflurane is insufficient to affect spontaneous recovery from mivacurium.14 We do not think that in this study any isoflurane-induced effect was of clinical importance.
All patients were pre-medicated with atropine 0.01 mg kg1. Atropine inhibits the activity of sweat glands, and the skin becomes hot and dry. Brown15 noted that sweating may be depressed sufficiently to raise the body temperature, although only after large doses of atropine are given.15 Although Brown15 did not define the dose of atropine that caused hyperthermia, he noted that therapeutic doses of 0.51.0 mg did not do so.
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References |
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2 Mourier A, Bigard AX, de Kerviler E, et al. Combined effects of caloric restriction and branched-chain amino acid supplemen tation on body composition and exercise performance in elite wrestlers. Int J Sports Med 1997; 18: 4755
3 Selldén E, Bränström R, Brundin T. Augmented thermic effect of amino acids under general anaesthesia occurs predominantly in extra-splanchnic tissues. Clin Sci 1996; 91: 4319
4 Mero A. Leucine supplementation and intensive training. Sports Med 1999; 27: 34758[ISI][Medline]
5 Freund H, Yoshimura N, Lunetta L, Fisher JE. The role of the branched-chain amino acids in decreasing muscle catabolism in vivo. Surgery 1978; 83: 6118[ISI][Medline]
6 Selldén E, Lindahl SGE. Postoperative nitrogen excretion after amino acid-induced thermogenesis under anesthesia. Anesth Analg 1998; 87: 6416[Abstract]
7 Selldén E, Brundin T, Wahren J. Augmented thermic effect of amino acids under general anaesthesia: a mechanism useful for prevention of anaesthesia-induced hypothermia. Clin Sci 1994; 86: 6118[ISI][Medline]
8 Selldén E, Bränström R, Brundin T. Preoperative infusion of amino acids prevents postoperative hypothermia. Br J Anaesth 1996; 76: 22734
9 Eriksson LI, Viby-Mogensen J, Lennmarken C. The effect of peripheral hypothermia on a vecuronium-induced neuro muscular block. Acta Anaesthesiol Scand 1991; 35: 38792[ISI][Medline]
10 Eriksson LI, Lennmarken C, Jensen E, Viby-Mogensen J. Twitch tension and train-of-four ratio during prolonged neuromuscular monitoring at different peripheral temperatures. Acta Anaesthesiol Scand 1991; 35: 24752[ISI][Medline]
11 Brundin T, Wahren J. Effects of iv amino acids on human splanchnic and whole body oxygen consumption, blood flow and blood temperatures. Am J Physiol 1994; 266: 396402
12 El-Gamal N, El-Kassabany N, Frank SM, et al. Age related thermoregulatory differences in a warm operating room environment (approximately 26°C). Anesth Analg 2000; 90: 6948
13 Sessler DI, McGuire J, Moayeri A, et al. Isoflurane-induced vasodilation minimally increases cutaneous heat loss. Anesthesiology 1991; 74: 22632[ISI][Medline]
14 Jalkanen L, Meretoja OA. The influence of the duration of isoflurane anaesthesia on neuromuscular effects of mivacurium. Acta Anaesthesiol Scand 1997; 41: 24851[Medline]
15 Brown JH. Atropine, scopolamine, and related antimuscarinic drugs. In: Gilman AG, eds. Goodman and Gilmans The Pharmacological Basis of Therapeutics, 8th Edn. New York: Pergamon Press, 1990; 15065