Beta-endorphin, cortisol and postoperative delirium: a preliminary report.

A transient delirium, including hallucinations and disorientation, occurred at some time during a 48 to 72 hr postoperative period in patients recovering from elective surgery in an intensive care unit. The occurrence of delirium in these patients was associated with a significant and unusually prolonged postoperative increase in circulating levels of beta-endorphin (B-endorphin) and cortisol, and a total disruption of normal plasma circadian rhythms of B-endorphin and cortisol. Postoperative mean 24-hr plasma levels of B-endorphin and cortisol were not significantly different from preoperative baseline levels in those patients who did not exhibit post-surgical delirium. Circadian rhythms of B-endorphin and cortisol in the non-delirious patients also remained normal following surgery, although peak plasma concentrations were significantly phase-shifted to later in the day. A disruption in circadian rhythms of the endogenous opiate/hypothalamic-pituitary-adrenal axis may represent an important component of post-operative psychological changes that are frequently observed in the intensive care unit setting.

Prognostic factors to predict outcome following the administration of hypertonic/hyperoncotic solution in hypovolemic patients.

Hypertonic solutions effectively improve hemodynamic parameters in patients admitted to the emergency room. However, no significant differences in outcome were observed compared with standard isotonic treatment in most previously published studies. This study evaluates pretreatment prognostic factors that predict a beneficial effect of hypertonic solution in patients admitted to the emergency room with hemorrhagic hypovolemia in a prospective double-blind fashion. The patients (n = 212) were randomized upon admission to receive 250 mL intravenous (i.v.) bolus of hypertonic 7.5% NaCl + 6% dextran (HSD, n = 101), or isotonic 0.9% NaCl solutions (IS, n = 111) as the first treatment, followed by standard resuscitation. Pretreatment factors assessed were sex, age, cause of hypovolemia, revised trauma score (RTS), Glasgow index, and mean arterial pressure (MAP) on admission. Both groups were compared for survival at 24 h and 30 days postadmission. Infused volumes were registered. HSD administration significantly increased MAP and reduced i.v. crystalloid infusions to maintain hemodynamic parameters, compared with IS. There was no difference between groups in the number of blood transfusions administered. Overall complication rates in both groups were similar (24%). There was a significant difference (p < .03) in overall (30 days) survival rate between HSD (73%) and IS (64%) groups. The 24 h survival rate was significantly lower in IS (72%) compared with HSD (87%); p < .01. Multivariate analyses showed that RTS and MAP were identified as independent predictors for 24 h survival in the group that received HSD. When evaluated for overall survival rate, hypertonic infusion benefited significantly only patients with MAP < 70 mmHg (p < .01).

The effect of severe trauma on urine loss of insulin.

Six trauma patients and five healthy volunteers were given an intravenous glucose infusion (5 Gm. per hour) for 6 hours. The serum insulin response and urine insulin excretion were measured and compared in the two groups. Glucose intolerance and serum insulin levels which were elevated but inappropriately low for the degree of glycemia characterized the trauma patients. Urine insulin concentrations and total urine insulin were increased significantly in the trauma patients. Renal function was similar in both groups, as determined by serum creatinine, blood urea nitrogen, and creatinine clearance. The increase in urine insulin concentration in the trauma patients reflected the higher serum insulin concentrations, but no correlation existed between serum insulin and urine insulin concentrations. A negative correlation was found between "insulin clearance" and serum insulin in both groups, indicating altered renal handling of insulin following injury which may be a contributory factor to the relative hypoinsulinemia of trauma.

The role of lung innervation in the hemodynamic response to hypertonic sodium chloride solutions in hemorrhagic shock.

The role of pulmonary innervation in the genesis of hemodynamic responses to hypertonic salt solutions was assessed in an animal model of total lung denervation by total division of the pulmonary hilum followed by reimplantation of the organ. This was performed in 10 mongrel dogs (weighing 12 to 20 kg) randomly assigned to two groups: group I (five dogs) was comprised of animals with catheters placed in the pulmonary artery of the denervated lung; group II (five dogs) was comprised of animals with catheters placed in the pulmonary artery of the intact lung; a control group (group III) (five dogs) was submitted to a sham thoracotomy with catheters inserted in either pulmonary artery. On the seventh postoperative day the mean arterial pressure (MAP) was monitored and severe hemorrhagic shock (MAP = 40 mm Hg) was produced in all animals. After 30 minutes of shock the shed blood was discarded and 5% of the shed volume (+/- 2 ml/kg) was infused through the pulmonary catheter in the form of a hypertonic NaCl solution (2400 mosm/L). MAP continued to be measured for the 30 minutes following the infusion period. A significant rise of MAP was uniformly observed in animals of groups II and III. In group I low elevations of MAP were observed during the infusion period, followed by a return to shock levels on discontinuation of the infusion. The results suggest that selective lung denervation abolished the beneficial cardiovascular effects of hypertonic NaCl infusion during resuscitation from severe hemorrhagic shock without affecting the plasma osmolality pattern.

Hypertonic solutions in the treatment of hypovolemic shock: a prospective, randomized study in patients admitted to the emergency room.

BACKGROUND: The infusion of small volumes of hypertonic saline solution or hypertonic saline plus dextran 70 is remarkably effective in restoring adequate hemodynamic conditions after hypovolemic shock. This prospective double-blind study compares the immediate hemodynamic effects of a bolus infusion of 7.5% NaCl or 7.5% NaCl plus 6% dextran 70 (both 2400 mOsm/L) in severe hypovolemia. METHODS: One hundred five adult patients admitted in hypovolemic shock (systolic blood pressure less than 80 mm Hg) were revived on arrival to the emergency room and administration of a 250 ml intravenous bolus of hypertonic saline solution (n = 35), hypertonic saline plus dextran (n = 35), or isotonic saline solution (n = 35). This infusion was immediately followed by standard crystalloid and blood replacement until systolic pressure reached 100 mm Hg. Mean arterial pressure (MAP) was measured every 5 minutes, and all intravenous infusions were registered. Plasma volume expansion was calculated from plasma protein concentration measurements. Patients were followed up throughout their hospital course, and results of treatment were recorded. RESULTS: At the end of the infusion period, and 5 and 10 minutes after infusion, MAP was significantly higher in patients receiving either hypertonic solution, compared with the group receiving isotonic solution. All groups showed similar trends toward restoration of hemodynamic parameters thereafter. The calculated plasma volume expansion, immediately after the bolus infusion, was significantly higher (24.1% +/- 1.8% and 24.9% +/- 1.1%) in the hypertonic groups, compared with isotonic groups (7.9% +/- 1.3%). Significantly greater volumes of fluids were required to restore systolic pressure in the patients receiving isotonic saline solution than in the groups receiving hypertonic solution. There were no significant differences between the groups receiving hypertonic solutions. The incidence of complications was low, and the mortality rate was similar in all groups. CONCLUSIONS: Infusion of 250 ml hypertonic saline solution in patients with severe hypovolemia was not related to any complications, nor did it affect mortality rates; it improved MAP significantly, acutely expanded plasma volume by 24%, and reduced significantly the volumes of crystalloids and blood required in their resuscitation.

Insulin half-life in man after trauma.

To explore the possibility that the half-life of insulin changes after trauma, five control subjects and 19 severe trauma patients received intravenous glucose (0.5 gm/kg) in 5 minutes to raise rapidly the insulin levels, followed immediately by 300 mg of intravenous diazoxide over 5 minutes to inhibit any further insulin secretion. Serial blood samples were analyzed for immunoreactive insulin, and insulin half-life was calculated. The baseline insulin level was 13.4 +/- 3.8 microU/ml in the trauma group 10.4 +/- 3.1 microU/ml in the control group. During the glucose infusion, insulin levels rose to 177.0 +/- 56.0 microU/ml in the controls and to 127.0 +/- 27.0 microU/ml in the trauma group. The rise in the control subjects was greater (P less than 0.03) than the rise in the trauma patients. After diazoxide, insulin levels fell to 25.0 +/- 6.2 microU/ml and 25.0 +/- 6.6 microU/ml, respectively. Insulin half-life in the control subjects was 5.2 +/- 0.3 min and 3.9 +/- 0.2 min in the trauma group (P less than 0.019).

Adenomyomatosis of the gallbladder.

Adenomyomatosis of the gallbladder is characterized by hyperplasia of the mucosa and hypertrophy of the muscularis which may result from a functional obstruction to the outflow of bile. The resulting increased intracystic pressure results in invagination of the mucosa through the muscularis as intramural diverticula which may be diffuse, segmental or localized. From a series of 1,500 patients who had cholecystectomies performed during a 10 year period, 9 patients presented with symptoms indistinguishable from calculous cholecystitis and were found to have a pathologic diagnosis of adenomyomatosis without other pathologic findings. The striking feature in this group of patients was the chronicity of the symptoms before surgery (mean 7.7 years). During this time, eight of the nine patients underwent repeated radiologic investigation of the upper gastrointestinal tract for frequent symptoms. Surgical treatment led to the disappearance of symptoms in eight of the nine patients and marked improvement in the remaining patient. The presence of adenomyomatosis in a patient presenting with a symptom complex similar to that of calculous cholecystitis is an indication for cholecystectomy.

The effects of surgery on the circadian rhythms of cortisol.

The circadian rhythms of plasma cortisol levels are studied extensively. Frequent sampling techniques are used to examine the effects of surgical trauma on the circadian pattern of plasma cortisol in man. Five patients were studied, 48 hours before and 48 hours after major surgery. The normal preoperative cortisol rhythms of these patients did not disappear after surgical trauma but they were significantly phase-shifted. In addition, the mean cortisol concentrations were significantly elevated and the intracircadian cycles suffered complex changes in the postoperative period.

Homologous dura mater used to close thoracic wall and diaphragmatic defects.

We have reported the successful use of homologous dura mater preserved in glycerin at room temperature to repair large defects of the thoracic wall or diaphragm in five patients. The surgical technic involved the use of autologous bone grafts in order to stabilize the thoracic cage in one case, but in the other four the dural blade was sufficient. The postoperative course was uneventful regarding the structure and function of the dural implant in each case.

Temporal characteristics of cortisol metabolism in adrenalectomized primates.

The rhythmicities observed in the plasmatic levels of cortisol are generally attributed to rhythms of production and release of the hormone. Since the plasmatic concentration of any given substance is a function of its production and its removal from the circulation, it is conceivable that the metabolism of cortisol also occurs in an oscillating fashion. To test this hypothesis Rhesus monkeys were submitted to bilateral adrenalectomy; cortisol was replaced at a constant infusion rate while blood was sampled at hourly intervals for the measurement of cortisol plasma levels. Rhythmic oscillations in the cortisol levels were observed. These rhythms exhibited two major components: a circadian and an ultradian component. The authors suggest that these rhythms be considered whenever normal or pathologic hormone rhythmicities are analyzed.

First annual Arnar-Stone lecture: The importance of the endocrine and metabolic responses to shock and trauma.

Trauma and shock result in activation of a wide variety of endocrine and metabolic systems. Based upon experimental work demonstrating metabolic deficits, a variety of metabolic therapies have been developed to assist in the treatment of patients with shock or trauma. Evidence to date is inconclusive as to whether this therapy will be of significant benefit to critically ill patients. Some of the senior author's previous research has been analyzed as it relates to important health policy issues. We suggest that a peer review mechanism be set up within organized professional groups to assess major research trends and develop informed opinions on key research subjects within their domain. These peer review assessments must be effectively communicated to Congress and the executive branch of the government, as well as to the general public, if support commensurate with the importance of the research is to be achieved.

Biosynthesis of glycosylated hemoglobins in the monkey.

We have investigated the in vivo biosynthesis of the minor hemoglobin components in the rhesus monkey. The elution profile of rhesus hemolysate on BioRex 70 cation exchange resin was analogous to that of human hemolysate. The rhesus Hb Alc peak was identified with the TBA test, which revealed a carbohydrate content identical to that of human Hb A1c. A rhesus monkey was injected with autologous 55Fe-bound transferrin, and the specific activity of each of the minor and major components was followed for over 70 days. As previously shown in man, rhesus Hb alc accumulated specific activity almost linearly over the erythrocyte life-span, indicative of slow and continuous conversion of Hb A0 to Hb Alc. This study revealed two new findings. (1) The specific activity of rhesus Hb Alb was always significantly less than that of Hb Alc. This result suggested that HB Alb is made by further posttranslational modification of Hb Alc. (2) The first portion of rhesus Hb A0 to be eluted on BioRex 70 contained a significant amount of carbohydrate and lower initial specific radioactivity than did the latter portion. This unexpected heterogeneity in the major hemoglobin component reflects slow, nonenzymatic glycosylation at sites other than at the N-terminus of the beta-chain.

Rectal sphincter reconstruction in perineal colostomies after abdominoperineal resection for cancer.

A surgical technique is proposed for the reconstruction of the anal sphincter in perineal colostomies after abdominoperineal resection for cancer. The procedure, which employs the gracilis muscle for the sphincteric reconstruction is described and the operative results and complications are analysed in 24 patients submitted to this type of surgery. Of the 22 patients who were followed up, 17 had excellent or good results with retention of solid or soft stools. Three patients had poor results with no voluntary retention, while 2 others were partly incontinent of solid faeces. In this group of 5 patients, 3 had stenosis of the colostomy and 1 had no sensibility of impending defaecation.

The effect of major trauma on the pathways of thyroid hormone metabolism.

In order to evaluate the effects of severe trauma on the levels of thyroxine (T4), 3,3',5-triiodothyronine (T3), and 3,3',5'-triiodothyronine (reverse-T3, r-T3), blood samples were collected from traumatized patients on the first post-trauma day. The plasma concentrations of T3 were significantly decreased (mean, 47.4 ng/dl); T4 levels were in the normal range (mean, 6.6 mcg/dl) and r-T3 levels were significantly elevated (mean, 80.8 ng/dl). The oxygen extraction by the muscular tissue was also determined in these patients and found to be elevated; however, no correlation could be established between the extraction ratios and the thyroid hormone levels. This deviation in the peripheral conversion of T4 into r-T3 with a decreased production of T3 also accompanies severe systemic illnesses and probably represents a form of T4 inactivation conditioned by the metabolic demands of the body. This alternate pathway of thyroid hormone metabolism is enhanced by elevated blood levels of catecholamines, glucose, or glucocorticoids as well as by decreased insulin plasma concentrations, all known to follow major trauma and other catabolic conditions.

Prolonged disruption of plasma beta-endorphin dynamics following surgery.

The purpose of the present study was to examine the effects of surgery on plasma beta-endorphin dynamics. Plasma beta-endorphin levels were measured by liquid chromatography/radioimmunoassay in seven patients undergoing elective surgery. Blood samples were obtained every 4 hr for two 24-hr periods: one beginning 48 hr before surgery and the other beginning 48 hr after surgery. Computer analysis of beta-endorphin levels as a function of clock time demonstrated a true circadian rhythm preoperatively with a mean of 28.0 +/- 5.9 pg/ml. In the postoperative period mean beta-endorphin levels were significantly elevated (85.6 +/- 20.7 pg/ml, P less than 0.005). Surgical procedures caused significant phase shifting in the grouped mean circadian rhythm of plasma beta-endorphin (mean = 2.4 hr). When the data was analyzed individually, plasma circadian rhythms were found to be totally abolished in the three patients with the longest operative times (mean = 3.8 hr) and significantly displaced in time in the remaining four patients. These prolonged alterations in plasma endogenous opioid peptide levels following surgery have not been previously reported, and should be considered in the management of the postsurgical patient.