Amino acid-induced thermogenesis during anaesthesia
Abstract: General anaesthesia causes hypothermia due to decreased metabolic rate and impaired thermoregulation. Adverse effects of hypothermia are coagulation disorders, wound infection, ischemic cardiac events and postoperative shivering. Many warming devices are in use to prevent heat loss, but little attention is paid to stimulate the body's own heat generation. All nutrients raise energy expenditure, and the highest diennic effect is ascribed to amino acids and proteins, 30-40 % in the awake state. In patients with complete cervical spinal cord injury and disrupted nervous connections between the brain and periphery, a normal thermogenesis was found in response to amino acids, indicating that central sympathetic nervous activation is not obligatory for amino acid-induced thermogenesis. It was suggested that nutrients stimulate heat production in peripheral tissues. The present studies were performed in order to determine if amino acids were able to exert diennogenic stimulation also during anaesthesia, which is known to silence central thermoregulation. The patients were studied before, during, and after abdominal surgery under isoflurane anaesthesia, and received either a mixture of 19 amino, acids, 240 kJ/h, or isovolunfic saline i.v. In two studies, awake healthy subjects participated, receiving equal amino acid infusions. The methods employed were: catheterization for measurements of mixed venous blood temperature, total and splanchnic blood flow, arterio-venous oxygen differences and oxygen uptake; indirect calorimetry for pulmonary oxygen uptake measurements in the awake state; rectal temperature measurements; analyses of plasma concentrations of catecholamines and amino acids; analyses of urinary nitrogen excretion. The measuring accuracy of the blood thermometry equipment was ±0.0010C. During anaesthesia and surgery, the decrease in core body temperature from baseline was significantly greater in control patients, 0.72±0.07 0C/h, than in amino acid treated patients, 0.31±0.05 0C/h (P<0.001). Anaesthesia during 34±4 min before surgery reduced pulmonary oxygen uptake by 145+9 ml/niin, or 47 W, in control patients and by 81±10 ml/min, or 26 W, in amino acid treated (P<001). The difference, 21 W, illustrates the thermogenic action of the amino acids, and may be compared with that of 4 W, observed in awake subjects after 30 min of identical amino acid infusion. Hence, thermic effect of amino acids is five-fold enhanced during general anaesthesia. At awakening, oxygen consumption increased to 55-70 % above baseline in amino acid treated patients. This restored core body temperatures to the pre-anaesthesia level without shivering. Whole body heat content during the entire period of anaesthesia decreased by 236±42 kJ in controls and by 67±20 kJ in amino acid patients (P<0.001), and thus approximately 70 % of the reduction in whole body heat content, caused by anaesthesia, was prevented by amino acid treatment. Postoperative hypothermia and shivering were counteracted irrespective of whether amino acids were given 1h prior to and during anaesthesia, or only during anaesdiesia. Amino acid infusion during 2 hrs prior to induction of anaesthesia raised body temperature by 0.3 0C/h, twice that observed in volunteers, who were not premedicated. This indicates an increased heat accumulation response to amino acids after premedication with lorazepam. The results altogether support the existence of an inhibitory action normally exerted by central thermosensors, in order to maintain oxidative metabolism within certain limits, to prevent hyperthermia. During anaesthesia, and possibly after lorazepam premedication, central thermosensors are silenced and hence, amino acid thermogenesis is exagerrated. Splanchnic oxygen uptake was unchanged in amino acid patients during anaesthesia and surgery and increased to 95±13 ml/min, or to 12±4 W above baseline at awakening. However, splanchnic tissues accounted for only 22-25 % of the enhanced thermogenesis in response to amino acids during anaesthesia, and at awakening. Thus, heat generation predominantly occurred in extra-splanchnic tissues, most probably in skeletal muscle. This may indicate an increased protein turnover, as both protein breakdown and synthesis are energy consuming processes, known to generate heat. However, oilier cellular mechanisms may also contribute to this non-shivering thermogenesis. Nitrogen excretion during 4 postoperative days, was unchanged from preoperative values in amino acid treated patients and decreased in control patients. Hence, the reduction in controls' nitrogen excretion most probably reflected a depressed metabolism, caused by anaesthetics, which was normalized in amino acid patients. It may be suggested that amino acid infusion provides substrates, otherwise mobilized from own tissues, needed for wound healing and immunological function. Multiple regression analysis showed that the most important variables predicting hospitalization were amino acid treatment (P<0.001), duration of surgery (P<0.001), and body temperature at awakening (P<0.01). As duration of surgery was similar in the two groups, and core body temperatures at awakening were due to amino acid infusions, these infusions were found to be the most important factor for the 2.7 days of shorter hospital stay as compared with in control patients.
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