H. Kehlet

Influence of Morphine Anaesthesia on the Endocrine‐Metabolic Response to Open‐Heart Surgery

Twelve patients scheduled for aortic valve replacement during extracorporal circulation were randomly allocated to either morphine anaesthesia or fluroxene anaesthesia. Morphine in a total dose of 4 mg/kg was administered bcforc skin incision. At the start of extracorporal circulation all patients received 25 g glucose intravascularly. The endocrine‐metabolic response to surgery, as expressed by changes in plasma ACTH, cortisol, insulin, growth hormone, cyclic adenosine ‐3′, ‐5′‐monophosphate (cyclic AMP), glucose, free fatty acids, blood b‐hydroxy‐butyrate and cumulative nitrogen balance was measured before and during anaesthesia and surgery, and on the first five post‐operative days.

Epidural Analgesia Inhibits the Renin and Aldosterone Response to Surgery

Renin activity and aldosterone concentration in plasma and excretion of sodium and potassium in urine were measured during a period of 24 hours in 12 patients undergoing hysterectomy under general anaesthesia or epidural analgesia. Analgesia extended from T4 to S5 and was effective throughout the study. The normal stress‐induced increase in plasma renin activity and aldosterone was inhibited by epidural analgesia. Urinary excretion of potassium was significantly lower in the epidural group, but sodium and water retention showed no difference between groups. It is concluded that neurogenic stimuli from the surgical area are important release mechanisms of the renin‐aldosterone response to surgery. The results suggest that post‐operative sodium retention is caused by factors other than the mineralocorticoid system.

Comparative effects of intrathecal bupivacaine and tetracaine on analgesia, cardiovascular function and plasma catecholamines

Forty otherwise healthy male patients, scheduled for elective inguinal herniotomy, were randomly allocated to spinal anaesthesia with 3 ml 0.5% hyperbaric tetracaine or bupivacaine under double‐blind conditions. The extent of blockade (pin‐prick and cold sensation), blood pressure and heart rate and plasma catecholamines were measured before and 5, 10, 15, 20 and 30 min after injection, before skin incision. Cephalad spread of sensory and temperature analgesia was insignificantly higher after tetracaine. The mean time taken to reach maximal spread of analgesia was 22 min in both groups. Mean arterial pressure showed a more pronounced decrease in the tetracaine group (22 vs 12%, P<0.009). Heart rate fell slightly and similarly in both groups, while rate‐pressure product was significantly lower in the tetracaine group. The correlation between the decrease in mean arterial pressure and the cephalad spread of sensory analgesia was similar in the two groups, suggesting that at identical levels of sensory analgesia changes in blood pressure were similar after tetracaine and bupivacaine. Plasma norepinephrine and epinephrine measurements before spinal puncture and at maximal decrease in mean arterial pressure showed a depressed response to fall in blood pressure in the tetracaine group. It is concluded that spinal anaesthesia with 3 ml hyperbaric 0.5% tetracaine is followed by a more pronounced fall in blood pressure compared to an identical dose of bupivaeaine. The more pronounced sympathetic blockade, confirmed by plasma catechoiamine measurements, following tetracainc is probably due to a higher cephalad spread of neurogenic blockade, rather than a differential effect on sympathetic nerve fibres.

Influence of Age on the Endocrine-metabolic Response to Surgery

The pathogenesis of the increased operative risk in elderly patients is unknown. From a theoretical point of view, a change in endocrine-metabolic response might be involved. In the present study, a battery of hormonal and metabolic variables were measured in eight young and eight elderly healthy males undergoing elective inguinal hernial repair under general anesthesia. Blood was drawn before induction of anesthesia, at skin incision, and one, two, and six hours after skin incision. The findings were: 1) Plasma cortisol increase was significantly higher in elderly than in young controls. 2) Plasma renin level was lower in old age, but renin-aldosterone and electrolyte response patterns were alike in the two groups. 3) Thyroid parameters, in terms of serum T4, serum T3, serum rT3, and T3-resin uptake, responded normally to surgery and showed no age-related differences. 4) The hyperglycemic response was not significantly influenced by age indicating unchanged glycoregulatory mechanisms also verified by determinations of plasma catecholamines, cAMP, and insulin. 5) Blood lymphocyte count was constantly lower in elderly than in young and decreased with time, but the age-related difference was not significant. 6) Blood polymorphonuclear leukocytes showed an increase of the same magnitude in both age groups, although at a significantly slower rate in the elderly. It is concluded that age affects some aspects of the initial endocrine-metabolic response to surgery.

Variation in spread of analgesia and loss of temperature discrimination during intermittent postoperative epidural bupivacaine administration

The proximal‐distal and bilateral extent of analgesia and loss of temperature discrimination were assessed during the initial 34.5 h after major abdominal surgery in ten patients receiving intermittent epidural bupivacaine injections according to a fixed dose regimen, Segmental spread of loss of temperature discrimination was invariably larger than analgesia at all times. During the later postoperative period (24–34 h) a pronounced intra‐individual variation in both proximal‐distal and bilateral spread of analgesia was observed despite identical epidural injections of bupivacaine. This variation in extent of analgesia was observed during injections of both 0.5% and 0.25% bupivacaine. The explanation of this observation is unknown but it may be shifts in catheter position, a variable disposition of the local anaesthetic agent or changes in the epidural space rather than tachyphylaxis.

Influence of Epidural Opiates on Postoperative Morbidity and Endocrine-Metabolic Changes

The advantages of epidural opiates for the relief of postoperative pain have been repeatedly demonstrated during recent years [1, 12, 14, 16]. Simultaneously, a variety of both respiratory and nonrespiratory side effects of epidural opiates have been described, including pruritus, nausea, vomiting, and urinary dysfunction [2, 14]. However, besides the alleviation of postoperative pain, considerable uncertainly remains as to other possible advantageous effects of epidural opiates on postoperative morbidity parameters such as pulmonary,cardiac, or thromboembolic complications, postoperative recovery of gastrointestinal function, ambulation and convalescence, etc. The large number of studies on pain relief not with standing, there is an unexpected lack of information on factors influencing postoperative morbidity because these investigations have primarily focused on the immediately postoperative period. Presented here is a short review of current knowledge derived from controlled studies on the influence of epidural opiate administration on various parameters of postoperative morbidity.