Postoperative Insulin Research Articles

Glucose Control Lowers the Risk of Wound Infection in Diabetics After Open Heart Operations

Background. Elevated blood glucose levels in the postoperative period are associated with an increased risk of deep wound infection in diabetic individuals undergoing open heart operations at Providence St. Vincent Hospital.Methods. Of 8,910 patients who underwent cardiac operations between 1987 and 1993, 1,585 (18%) were diabetic. The rate of deep sternal wound infections in diabetic patients was 1.7%, versus 0.4% for nondiabetics. Nine hundred ninety patients had their operation before implementation of the protocol and 595 after implementation. Charts of all diabetic patients were reviewed. Mean blood glucose levels were calculated from documented results of finger-stick glucometer testing.Results. Thirty-three diabetic patients suffered 35 deep wound infections: 27 sternal (1.7%) and eight at the donor site (0.5%). Infected diabetic patients had a higher mean blood glucose level through the first 2 postoperative days than noninfected patients (208 ± 7.1 versus 190 ± 0.8 mg/dL; p < 0.003) and had a greater body mass index (31.5 ± 1.4 versus 28.6 ± 0.1 kg/m2; p < 0.05). Multivariable logistic regression showed that mean blood glucose level for the first 2 days (p = 0.002), obesity (p < 0.002), and use of the internal mammary artery (p < 0.02) were all independent predictors of deep wound infection. Institution of a protocol of postoperative continuous intravenous insulin to maintain blood glucose level less than 200 mg/dL was begun in September 1991. This protocol resulted in a decrease in blood glucose levels for the first 2 postoperative days and a concomitant decrease in the proportion of patients with deep wound infections, from 2.4% (24/990) to 1.5% (9/595) (p < 0.02).Conclusions. The incidence of deep wound infection in diabetic patients was reduced after implementation of a protocol to maintain mean blood glucose level less than 200 mg/dL in the immediate postoperative period.(Ann Thorac Surg 1997;63:356–61)

O.61 Infusions of insulin and glucose before surgery abolish immediate postoperative insulin resistance

O.61 Infusions of insulin and glucose before surgery abolish immediate postoperative insulin resistance

Preoperative Gastric Emptying Effects of Anxiety and Oral Carbohydrate Administration

Overnight fasting is routine before elective surgery. This may not be the optimal way to prepare for surgical stress, however, because intravenous carbohydrate supplementation instead of fasting has recently been shown to reduce postoperative insulin resistance. In the current study, gastric emptying of a carbohydrate-rich drink was investigated before elective surgery and in a control situation. Twelve patients scheduled for elective surgery were randomly given 400 mL of either a carbohydrate-rich drink (285 mOsm/kg, 12.0% carbohydrates, n = 6) or water 4 hours before being anesthetized. Gastric emptying was measured (gamma camera, 99Tcm). Each patient repeated the protocol postoperatively as a control. All values were presented as the mean +/- SEM by means of a nonparametric statistical evaluation. Despite the increased anxiety experienced by patients before surgery (p < 0.005), gastric emptying did not differ between the experimental and control situations. Initially, water emptied more rapidly than carbohydrate. However, after 90 minutes, the stomach was emptied regardless of the solution administered (3.2 +/- 1.1% [mean +/- SEM] remaining in the stomach in the carbohydrate group versus 2.3 +/- 1.2% remaining in the stomach in the water group). Preoperative anxiety does not prolong gastric emptying. The stomach had been emptied 90 minutes after ingestion of both the carbohydrate-rick drink and water, thereby indicating the possibility of allowing an intake of iso-osmolar carbohydrate-rich fluids before surgery.

Autologous Islet Transplantation to Prevent Diabetes After Pancreatic Resection

Background Extensive pancreatic resection for small-duct chronic pancreatitis is often required for pain relief, but the risk of diabetes is a major deterrent. Objective Incidence of pain relief, prevention of diabetes, and identification of factors predictive of success were the goals in this series of 48 patients who underwent pancreatectomy and islet autotransplantation for chronic pancreatitis. Patients and Methods Of the 48 patients, 43 underwent total or near-total (>95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas was dispersed by either old (n = 26) or new (n = 22) methods of collagenase digestion. Islets were injected into the portal vein of 46 of the 48 patients and under the kidney capsule in the remaining 2. Postoperative morbidity, mortality, pain relief, and need for exogenous insulin were determined, and actuarial probability of postoperative insulin independence was calculated based on several variables. Results One perioperative death occurred, Surgical complications occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48 patients had a transient increase in portal venous pressure after islet infusion, but no serious sequelae developed. More than 80% of patients experienced significant pain relief after pancreatectomy. Of the 39 patients who underwent total or near-total pancreatectomy, 20 (51%) were initially insulin independent. Between 2 and 10 years after transplantation, 34% were insulin independent, with no grafts failing after 2 years. The main predictor of insulin independence was the number of islets transplanted (of 14 patients who received >300,000 islets, 74% were insulin independent at >2 years after transplantation). In turn, the number of islets recovered correlated with the degree of fibrosis (r = −0.52, p = 0.006) and the dispersion method (p = 0.005). Conclusion Pancreatectomy can relieve intractable pain caused by chronic pancreatitis. Islet autotransplantation is safe and can prevent long-term diabetes in more than 33% of patients and should be an adjunct to any pancreatic resection. A given patient's probability of success can be predicted by the morphologic features of the pancreas.

Autologous islet transplantation to prevent diabetes after pancreatic resection.

Extensive pancreatic resection for small-duct chronic pancreatitis is often required for pain relief, but the risk of diabetes is a major deterrent. Incidence of pain relief, prevention of diabetes, and identification of factors predictive of success were the goals in this series of 48 patients who underwent pancreatectomy and islet autotransplantation for chronic pancreatitis. Of the 48 patients, 43 underwent total or near-total (> 95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas was dispersed by either old (n = 26) or new (n = 22) methods of collagenase digestion. Islets were injected into the portal vein of 46 of the 48 patients and under the kidney capsule in the remaining 2. Postoperative morbidity, mortality, pain relief, and need for exogenous insulin were determined, and actuarial probability of postoperative insulin independence was calculated based on several variables. One perioperative death occurred. Surgical complications occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48 patients had a transient increase in portal venous pressure after islet infusion, but no serious sequelae developed. More than 80% of patients experienced significant pain relief after pancreatectomy. Of the 39 patients who underwent total or near-total pancreatectomy, 20 (51%) were initially insulin independent. Between 2 and 10 years after transplantation, 34% were insulin independent, with no grafts failing after 2 years. The main predictor of insulin independence was the number of islets transplanted (of 14 patients who received > 300,000 islets, 74% were insulin independent at > 2 years after transplantation). In turn, the number of islets recovered correlated with the degree of fibrosis (r = -0.52, p = 0.006) and the dispersion method (p = 0.005). Pancreatectomy can relieve intractable pain caused by chronic pancreatitis. Islet autotransplantation is safe and can prevent long-term diabetes in more than 33% of patients and should be an adjunct to any pancreatic resection. A given patient's probability of success can be predicted by the morphologic features of the pancreas.

Glucose Infusion Instead of Preoperative Fasting Reduces Postoperative Insulin Resistance

Comment: It is not apparent from the presentation of data what amounts of glucose were given during the study. A 70-kg patient having a preoperative infusion for a 12-hr period would have received a total of 252 g of glucose. This was given as a 20% solution with 40 mmol of potassium chloride/L. In this example a total of 1260 mL of glucose solution would have been administered. Unfortunately there is no indication from the data as to the effect of this infusion on fluid balance. Any differences in intraoperative responses to stress as shown by hormone levels would not have been revealed by the present study protocol. However, as the authors point out in this discussion, the preservation of body glucose stores might have an advantageous effect should there be significant intraoperative hemorrhage. It must be stressed that this study was performed in patients without major systemic disease and in whom the operative intervention did not cause major metabolic problems. Thus, although a major preoperative glucose infusion may be to the advantage of surgical patients, it has still to be established whether this is so in the presence of other disease processes and what the effect on responses to intraoperative blood losses and other such problems may be. Moreover, given the ever-increasing percentage of patients coming to the hospital on the day of surgery, rather titan the night before surgery, one must question the feasibility of 12-hr preoperative glucose infusion.

Place des facteurs hormonaux anabolisants lors de chirurgie chez l'adulte

Hormonal agents with anabolic effect are virtually able to limit or even to counteract the adverse effects of stress and to act in synergy with nutritional support. Hormones with a high theoretic anabolic power include recombinant human growth hormone (rGH), insulin, insulin-like growth factor and testosterone. Other molecules favour anabolism in modifying the catabolic effect of diseases (anti-cytokines, beta-adrenoceptor agonists), in promoting intestinal absorption of substrates or in stimulating epithelial growth (EGF). The results of preliminary studies cannot be transferred into routine clinical practice. The rGH favours the preservation of body mass integrity and various functions. Therefore it could improve postoperative outcome and decrease the duration of hospital stay. A study in severely burnt children showed the metabolic benefits of rGH as well as a shortening of hospital stay because of a decrease of cicatrisation delay after skin grafting. Finally it demonstrated that rGH allows major financial savings in severe burns. The IGF-1 stimulates host defences and decreases the rate of wound infections. The rGH potentiates nitrogen sparing effect of IGF-1 and decreases hypoglycaemia induced by IGF-1. However a study on patients in stress is yet lacking. A combination of growth factors could be virtually efficient, however the cost seems exorbitant. An unquestionable evidence of their clinical efficiency is required before a clinical use in routine can be considered. The postoperative protein catabolism could be decreased by nandrolone decanoate or its derivatives. On the other hand, it has not been proven that protein synthesis, the muscle function or clinical prognosis can be improved by such a treatment. The benefit of postoperative insulin administration with an anabolic goal has not been demonstrated. Finally the use of anabolic agents during the postoperative period has at present not been sufficiently substantiated for being considered in routine clinical practice. Controlled trials on clinical outcome, benefit-cost and benefit-risk ratios are lacking. In patients with a preoperative hypothalamico-hypophyseo-adrenal axis or gonadal insufficiency (hypophyseal insufficiency, chronic respiratory insufficiency, castration), a perioperative substitutive hormonal administration is required in the frame of a long term therapeutic strategy.

Place des facteurs hormonaux anabolisants lors de chirurgie chez l'adulte

Hormonal agents with anabolic effect are virtually able to limit or even to counteract the adverse effects of stress and to act in synergy with nutritional support. Hormones with a high theoretic anabolic power include recombinant human growth hormone (rGH), insulin, insulin-like growth factor and testosterone. Other molecules favour anabolism in modifying the catabolic effect of diseases (anti-cytokines, beta-adrenoceptor agonists), in promoting intestinal absorption of substrates or in stimulating epithelial growth (EGF). The results of preliminary studies cannot be transferred into routine clinical practice. The rGH favours the preservation of body mass integrity and various functions. Therefore it could improve postoperative outcome and decrease the duration of hospital stay. A study in severely burnt children showed the metabolic benefits of rGH as well as a shortening of hospital stay because of a decrease of cicatrisation delay after skin grafting. Finally it demonstrated that rGH allows major financial savings in severe burns. The IGF-1 stimulates host defences and decreases the rate of wound infections. The rGH potentiates nitrogen sparing effect of IGF-1 and decreases hypoglycaemia induced by IGF-1. However a study on patients in stress is yet lacking. A combination of growth factors could be virtually efficient, however the cost seems exorbitant. An unquestionable evidence of their clinical efficiency is required before a clinical use in routine can be considered. The postoperative protein catabolism could be decreased by nandrolone decanoate or its derivatives. On the other hand, it has not been proven that protein synthesis, the muscle function or clinical prognosis can be improved by such a treatment. The benefit of postoperative insulin administration with an anabolic goal has not been demonstrated. Finally the use of anabolic agents during the postoperative period has at present not been sufficiently substantiated for being considered in routine clinical practice. Controlled trials on clinical outcome, benefit-cost and benefit-risk ratios are lacking. In patients with a preoperative hypothalamico-hypophyseo-adrenal axis or gonadal insufficiency (hypophyseal insufficiency, chronic respiratory insufficiency, castration), a perioperative substitutive hormonal administration is required in the frame of a long term therapeutic strategy.

Insulin Resistance after Abdominal Surgery

A study was carried out to determine the time course and degree of postoperative insulin resistance in patients undergoing elective abdominal surgery. Mean(s.e.m.) insulin sensitivity was determine ...

Effect of Diabetes Mellitus on Hepatic Resection

We evaluated the effect of diabetes mellitus on mortality and morbidity after elective hepatic resections. Of 209 patients who underwent hepatic resections between April 1985 and July 1990, 49 (23.4%) were diabetic. Postoperative morbidity was more common among diabetics than among nondiabetics (75.5% vs 51.3%), mainly due to hepatic decompensation (55.1% vs 36.3%) and intraperitoneal sepsis (18.4% vs 6.3%). However, their incidence of hospital death (2% vs 2.5%), mean +/- SD postoperative hospital stay (36.1 +/- 20.2 days vs 29.4 +/- 28.2 days), and long-term survival were comparable with those of nondiabetics. Diabetics with and without complications were similar in preoperative or postoperative insulin requirement, duration of diabetes, and preoperative fasting glucose. Nevertheless, all eight patients with 24-hour urinary glucose excretion above 1 g developed complications. We conclude that diabetics are at a high risk of morbidity, but not of mortality after elective hepatic resection.

Mediators of postoperative insulin resistance

Mediators of postoperative insulin resistance

Postoperative insulin resistance and muscle protein synthesis rate

Postoperative insulin resistance and muscle protein synthesis rate

Time course of postoperative insulin resistance

Time course of postoperative insulin resistance

Somatostatin and Thyrotrophin‐Releasing Hormone Response and Receptor Status of a Thyrotrophin‐Secreting Pituitary Adenoma: Clinical and in vitro Studies

Abstract We have described a patient with a thyrotrophin-secreting pituitary adenoma and correlated a detailed physiological and anatomical investigation of the surgically resected tumour with its in vivo regulation. Thyrotrophin secretion was inhibited by circulating thyroid hormones, dopaminergic agonists and the somatostatin analogue SMS 201-995 but could not be stimulated by thyrotrophin-releasing hormone or further inhibited by exogenous triiodothyronine. Prolonged treatment with SMS 201-995 caused tumour shrinkage as shown by successive computed tomography scans but was accompanied by tumour desensitization and the development of diabetes mellitus. This is the first thyrotroph adenoma in which somatostatin receptors have been directly demonstrated and shown to completely block thyrotrophin-releasing hormone-induced inositol phospholipid accumulation when occupied. In addition, preincubation with triiodothyronine significantly inhibited thyrotrophin-releasing hormone-induced inositol phospholipid turnover in dispersed pituitary cells indicating that in this tumour, circulating thyroid hormones were exerting feedback inhibition at the level of the pituitary either by reducing the number of thyrotrophin-releasing hormone receptors and/or their coupling to second messenger pathways. In keeping with this hypothesis, the acute reduction in intrapituitary triiodothyronine by sodium ipodate in vivo had no effect on peripheral thyrotrophin over 6 h suggesting that the onset of the effect of triiodothyronine withdrawal on thyrotrophin secretion was suitably delayed. The importance of the inositol phospholipid second messenger pathway in transducing the secretory response in this tumour was further corroborated by electrophysiological studies which demonstrated thyrotrophin-releasing hormone-induced changes in K(+) currents which are dependent on intracellular Ca(2+) ions, presumably mobilized via the inositol phospholipids. In addition to thyrotrophin and alpha subunit, growth hormone mRNA and growth hormone were found throughout the tumour as were two populations of cells distinguished electron microscopically by the size of their secretory granules. Although acromegalic features are not unusual in thyrotroph adenomas, our patient showed no evidence of inappropriate growth hormone secretion during surgery or in response to pre- or post-operative insulin stress tests.

Effect of Epidural Analgesia on Postoperative Insulin Resistance as Evaluated by Insulin Clamp Technique

Comment It is known that epidural anesthesia and postoperative analgesia can suppress the endocrine responses to surgical stimulation. High-dose narcotic anesthesia can do this also. This report confirms these effects with epidural anesthetics and narcotics and helps delineate the mechanism for postoperative insulin resistance. The insulin clamp technique is an interesting way of looking at this. It remains to be seen, however, whether reduction of this “stress response” in the perioperative period will actually result in less patient morbidity. Mark A. Rockoff, M.D.

'Entero-insular axis' and surgical trauma.

To study the optimal means of postoperative energy supply, three glucose loads (5 g, 15 g, 40 g) were given via the enteral or the parenteral route before and immediately after abdominal surgery. Pre- and post-operatively, glucose and insulin concentrations were strongly dose-related after both kinds of administration. But the postoperative insulin concentrations were higher than the preoperative ones. Likewise, in both test situations the 'insulinogenic index' was significantly higher postoperatively than preoperatively. After the enteral glucose load, however, the index was 3 to 10 times higher than after the parenteral one. According to these results, even in the early postoperative period the enteral route of glucose administration is not only feasible but seems also to be superior to the parenteral one.

Improvement of impaired postoperative insulin action by bradykinin.

The effect of bradykinin on insulin-stimulated glucose metabolism was studied in 5 operated patients using the euglycemic insulin clamp technique and the forearm catheter technique. Insulin infusion [1.0 mU/(kg b.w. X min)] raised plasma insulin levels up to 73 muU/ml. Euglycemia was maintained by a computerized glucose infusion rate, amounting to 2.9 mg/(kg b.w. X min). Addition of bradykinin [1.5 micrograms/(kg b.w. X h)] resulted in a significant increase of the glucose infusion rate [+ 1.0 mg/(kg b.w. X min)] indicating elevated whole body glucose uptake. This was related to an enhanced forearm glucose uptake [+ 1.16 mumol/(100 g X min)]. Forearm blood flow remained stable.

Reduction of postoperative insulin resistance by bradykinin infusion : [formula omitted], B.Günther, W.Hartl, F.Utz, K.Rett, M.Wicklmayr, G.Dietze (Chirurgische Klinik, LMU München, Klinikum Großhadern und Forschergruppe Diabetes, Med. Klinik, Krankenhaus München-Schwabing, FRG)

Reduction of postoperative insulin resistance by bradykinin infusion : [formula omitted], B.Günther, W.Hartl, F.Utz, K.Rett, M.Wicklmayr, G.Dietze (Chirurgische Klinik, LMU München, Klinikum Großhadern und Forschergruppe Diabetes, Med. Klinik, Krankenhaus München-Schwabing, FRG)

Serum Group I Pepsinogens after Consecutive Stimulations with Insulin and Pentagastrin in Unoperated Duodenal Ulcer Patients and in Duodenal Ulcer Patients after Proximal Gastric Vagotomy

Ten unoperated duodenal ulcer (DU) patients and 11 DU patients 1 year after proximal gastric vagotomy (PGV) were examined for gastric acid secretion and for serum group I pepsinogens (PG I) during basal conditions and after consecutive stimulations with insulin and pentagastrin. In unoperated DU patients insulin stimulation caused a significant increase both in gastric acid secretion and in serum PG I. In these patients a consecutive pentagastrin stimulation elicited a significant increase in gastric acid secretion but not in serum PG I. In patients after PGV, insulin stimulation caused a slight but significant increase in gastric acid secretion but not in serum PG I. In these patients a consecutive pentagastrin stimulation caused a significant increase both in gastric acid secretion and in serum PG I. Two of the operated patients had negative and nine had positive responses to the postoperative insulin test. According to this study, in consecutive stimulation with insulin and pentagastrin the effect of pentagastrin on serum PG I is inhibited by preceding insulin stimulation in DU patients. By PGV the effect of insulin on serum PG I is eliminated. and then a subsequent pentagastrin stimulation elicits a significant rise in serum PG I. As a test of the completeness of PGV, the serum PG I response to insulin-induced hypoglycemia seems to be less sensitive than the gastric acid response.

Loss of Insulin Response to Ingested Amino Acids After Jejunoileal Bypass Surgery for Morbid Obesity

Amino acid tolerance tests were performed before and after jejunoileal bypass surgery for morbid obesity to determine whether an enteric factor(s) originating in the bypassed jejunum and/or ileum potentiates the insulin response to oral nitrogen loading. Preoperatively a 30-gm. mixture of amino acids given orally evoked a larger peak insulin than an intravenous load yielding comparable plasma amino acid elevations (82 +/- 17 muU./ml versus 38 +/- 8 muU./ml., p less than 0.05). Four months after operation, basal insulin concentrations were 46 per cent (p less than 0.001) of preoperative values. After surgery the response to intravenous amino acids was preserved when expressed as percentage increase above basal. In contrast, the peak increment and the percentage increase in insulin secretion after 30-gm. oral amino acid loading was significantly blunted (p less than 0.005). A smaller amino acid load (16.5 gm.) was given preoperatively to duplicate the plasma amino acid elevations seen postoperatively with the 30-gm. mixture given by mouth. The insulin response postoperatively was still significantly lower (167 +/- 33 per cent versus 98 +/- 16 per cent, p less than 0.05). After various explanations for the diminished postoperative insulin release following oral amino acid ingestion are considered, the results are best explained by the loss of an enteric insulinotrophic factor(s) normally released by the bypassed portions of jejunum or ileum in response to ingested protein.