Validation of the Norwegian survival prediction model in trauma (NORMIT) in Swedish trauma populations.

BACKGROUND: Trauma survival prediction models can be used for quality assessment in trauma populations. The Norwegian survival prediction model in trauma (NORMIT) has been updated recently and validated internally (NORMIT 2). The aim of this observational study was to compare the accuracy of NORMIT 1 and 2 in two Swedish trauma populations. METHODS: Adult patients registered in the national trauma registry during 2014-2016 were eligible for inclusion. The study populations comprised the total national trauma (NT) population, and a subpopulation of patients admitted to a single level I trauma centre (TC). The primary outcome was 30-day mortality. Model validation included receiver operating characteristic (ROC) curve analysis and GiViTI calibration belts. The calibration was also assessed in subgroups of severely injured patients (New Injury Severity Score (NISS) over 15). RESULTS: A total of 26 504 patients were included. Some 18·7 per cent of patients in the NT population and 2·6 per cent in the TC subpopulation were excluded owing to missing data, leaving 21 554 and 3972 respectively for analysis. NORMIT 1 and 2 showed excellent ability to distinguish between survivors and non-survivors in both populations, but poor agreement between predicted and observed outcome in the NT population with overestimation of survival, including in the subgroup with NISS over 15. In the TC subpopulation, NORMIT 1 underestimated survival irrespective of injury severity, but NORMIT 2 showed good calibration both in the total subpopulation and the subgroup with NISS over 15. CONCLUSION: NORMIT 2 is well suited to predict survival in a Swedish trauma centre population, irrespective of injury severity. Both NORMIT 1 and 2 performed poorly in a more heterogeneous national population of injured patients.

ANTECEDENTES: Los modelos de predicción de supervivencia en los traumatismos pueden ser utilizados para la evaluación de la calidad en las poblaciones con traumatismos. Recientemente, el modelo noruego de predicción de supervivencia en traumatismos (NORMIT) se ha actualizado y validado internamente (NORMIT 2). El objetivo de este estudio observacional fue comparar la precisión de los modelos NORMIT 1 y 2 en dos poblaciones suecas con traumatismos. MÉTODOS: Pacientes adultos registrados en el registro nacional de traumatismos durante 2014-2016 fueron elegibles para el estudio. Las poblaciones de estudio eran: (1) la población total nacional de traumatismos (national trauma, NT) y (2) una subpoblación de pacientes ingresados en un único centro de trauma de nivel I (trauma centre, TC). El resultado primario fue la mortalidad a los 30 días. La validación del modelo incluyó curvas de características operativas del receptor y cinturones GiViTI de calibración. La calibración también se evaluó en subgrupos de pacientes con lesiones graves (New Injury Severity Score, NISS >15). RESULTADOS: Se incluyeron un total de 26.504 pacientes. La exclusión por falta de datos fue del 18,7% en la población NT (n = 21.554) y del 2,6% en la población TC (n = 3.972). Los modelos NORMIT 1 y 2 mostraron una habilidad excelente para distinguir entre supervivientes y no supervivientes en ambas poblaciones, pero con un grado de acuerdo pobre entre el resultado predicho y el observado en la población NT, con sobreestimación de la supervivencia incluido el subgrupo de NISS >15. En la subpoblación TC, NORMIT 1 subestimó la supervivencia independientemente de la gravedad de la lesión, pero NORMIT 2 mostró una buena calibración tanto en la subpoblación total, como en el subgrupo NISS >15. CONCLUSIÓN: El modelo NORMIT 2 es muy apropiado para predecir la supervivencia en la población de un centro de traumatismos sueco independientemente de la gravedad de la lesión. Los modelos tanto NORMIT 1 como NORMIT 2 funcionan mal en una población de traumatismos nacional más heterogenea.

Analysis of preventable deaths and errors in trauma care in a Scandinavian trauma level-I centre.

BACKGROUND: The wide disparity in the methodology of preventable death analysis has created a lack of comparability among previous studies. The guidelines for the peer review (PR) procedure suggest the inclusion of risk-adjustment methods to identify patients to review, that is, exclude non-preventable deaths (probability of survival [Ps] < 25%) or focus on preventable deaths (Ps > 50%). We aimed to, through PR process, (1) identify preventable death and errors committed in a level-I trauma centre, and (2) explore the use of different risk-adjustment methods as a complement. METHODS: A multidisciplinary committee reviewed all trauma patients, which died a trauma-related death, within 30 days of admission to Karolinska University Hospital, Stockholm, in the period of 2012-2016. Ps was calculated according to TRISS and NORMIT and their accuracy where compared. RESULTS: Two hundred and ninety-eight deaths were identified and 252 were reviewed. The majority of deaths occurred between 1 and 7 days. Ten deaths (4.0%) were classified as preventable. Sixty-seven errors were identified in 53 (21.0%) deaths. The most common error was inappropriate treatment in all deaths (21 of 67) and in preventable deaths (5 of 13). Median Ps in non-preventable deaths was higher than the cut-off (<25%) and Ps-TRISS was almost twice as high as Ps-NORMIT (65% vs 33%, P < .001). Two clinically judged preventable deaths with Ps <25% would have been missed with both models. Median Ps in preventable deaths was above the cut-off (>50%) and higher with Ps-TRISS vs Ps-NORMIT (75% vs 58%, P < .001). Three and 4 clinically judged preventable deaths would have been missed, respectively, for TRISS and NORMIT, if using this cut-off. CONCLUSION: Preventable deaths were commonly caused by clinical judgment errors in the early phases but death occurred late. Ps calculated with NORMIT was more accurate than TRISS in predicting mortality, but both perform poorly in identifying preventable and non-preventable deaths when applying the cut-offs. PR of all trauma death is still the golden standard in preventability analysis.

Assessing surgical quality: comparison of general and procedure-specific morbidity estimation models for the risk adjustment of pancreaticoduodenectomy outcomes.

INTRODUCTION: The use of outcomes to evaluate surgical quality implies the need for detailed risk adjustment. The physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) is a generally applicable risk adjustment model suitable for pancreatic surgery. A pancreaticoduodenectomy (PD)-specific intraoperative pancreatic risk assessment (IPRA) estimates the risk of postoperative pancreatic fistula (POPF) and associated morbidity based on factors that are not incorporated into POSSUM. OBJECTIVE: The aim of the study was to compare the risk estimations of POSSUM and IPRA in patients undergoing PD. METHODS: An observational single-center cohort study was conducted including 195 patients undergoing PD in 2008-2010. POSSUM and IPRA data were recorded prospectively. Incidence and severity of postoperative morbidity was recorded according to established definitions. The cohort was grouped by POSSUM and IPRA risk groups. The estimated and observed outcomes and morbidity profiles of POSSUM and IPRA were scrutinized. RESULTS: POSSUM-estimated risk (62 %) corresponded with observed total morbidity (65 %). Severe morbidity was 17 % and in-hospital-mortality 3.1 %. Individual and grouped POSSUM risk estimates did not reveal associations with incidence (p = 0.637) or severity (p = 0.321) of total morbidity or POPF. The IPRA model identified patients with high POPF risk (p < 0.001), but was even associated with incidence (p < 0.001) and severity (p < 0.001) of total morbidity. CONCLUSION: The risk factors defined by a PD-specific model were significantly stronger predictive indicators for the incidence and severity of postoperative morbidity than the factors incorporated in POSSUM. If available, reliable procedure-specific risk factors should be utilized in the risk adjustment of surgical outcomes. For pancreatic surgery, generally applicable tools such as POSSUM still have to prove their relevance.

Diagnostic value of abdominal drainage in individual risk assessment of pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: The use of prophylactic abdominal drainage following pancreaticoduodenectomy (PD) is controversial as its therapeutic value is uncertain. However, the diagnosis of postoperative pancreatic fistula (POPF), the main cause of PD-associated morbidity, is often based on drain pancreatic amylase (DPA) levels. The aim of this study was to assess the predictive value of DPA, plasma pancreatic amylase (PPA) and serum C-reactive protein (CRP) for diagnosing POPF after PD. METHODS: Patients undergoing PD with prophylactic drainage between 2008 and 2012 were studied prospectively. DPA, PPA and CRP levels were obtained daily. Differences between groups with clinically relevant POPF (International Study Group on Pancreatic Fistula (ISGPF) grade B/C) and without clinically relevant POPF (no POPF or ISGPF grade A) were evaluated. Receiver operating characteristic (ROC) analyses were performed to determine the value of DPA, PPA and CRP in prediction of POPF. Risk profiles for clinically relevant POPF were constructed and related to the intraoperative pancreatic risk assessment. RESULTS: Fifty-nine (18.7 per cent) of 315 patients developed clinically relevant POPF. DPA, PPA and CRP levels on postoperative day (POD) 1-3 differed significantly between the study groups. In predicting POPF, the DPA level on POD 1 (cut-off at 1322 units/l; odds ratio (OR) 24.61, 95 per cent confidence interval 11.55 to 52.42) and POD 2 (cut-off at 314 units/l; OR 35.45, 14.07 to 89.33) was superior to that of PPA on POD 1 (cut-off at 177 units/l; OR 13.67, 6.46 to 28.94) and POD 2 (cut-off at 98 units/l; OR 16.97, 8.33 to 34.59). When DPA was combined with CRP (cut-off on POD 3 at 202 mg/l; OR 16.98, 8.43 to 34.21), 90.3 per cent of postoperative courses could be predicted correctly (OR 44.14, 16.89 to 115.38). CONCLUSION: The combination of serum CRP and DPA adequately predicted the development of clinically relevant pancreatic fistula following PD.

Structured intraoperative assessment of pancreatic gland characteristics in predicting complications after pancreaticoduodenectomy.

BACKGROUND: The morbidity rate after pancreaticoduodenectomy remains high (20-50 per cent) and postoperative pancreatic fistula (POPF) is a major underlying factor. POPF has been reported to be associated with pancreatic consistency (PC) and pancreatic duct diameter (PDD). The aim was to quantify the risk of pancreaticojejunostomy-associated morbidity (PJAM) by means of a structured intraoperative assessment of both characteristics. METHODS: This single-centre prospective observational study included pancreaticoduodenectomies performed between 2008 and 2010 with a standardized duct-to-mucosa end-to-side pancreaticojejunostomy. PC and PDD were assessed during surgery and classified into four grades each (from very hard to very soft, and from larger than 4 mm to smaller than 2 mm, respectively). PJAM was defined as POPF (grade B or C in International Study Group on Pancreatic Fistula classification) or symptomatic peripancreatic collection of either abscess or fluid. PJAM of at least Clavien grade IIIb was considered severe. RESULTS: PJAM and POPF were observed in 24 (21·8 per cent) and 17 (15·5 per cent) of 110 patients respectively. Softer PC and smaller PDD were risk factors for POPF (both P < 0·001), symptomatic peripancreatic collections (P = 0·071 and P = 0·015) and PJAM (both P < 0·001). Combining consistency and duct characteristics in a composite classification the PJAM risk was stratified as 'high' (both risk factors, PJAM incidence 51 per cent), 'intermediate' (softer PC or smaller PDD, PJAM 26 per cent) or 'low' (no risk factors, PJAM 2 per cent). Severe PJAM was observed only in patients with smaller PDD. CONCLUSION: A high-risk pancreatic gland had a 25-fold higher risk of PJAM after pancreaticoduodenectomy than a low-risk gland. This simple classification can contribute to more individualized patient management and allow stratification of study cohorts with homogeneous POPF risk.

Early intraperitoneal metabolic changes and protease activation as indicators of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Ischaemia and local protease activation close to the pancreaticojejunal anastomosis (PJA) are potential mechanisms of postoperative pancreatic fistula (POPF) formation. To provide information on the pathophysiology of POPF, intraperitoneal microdialysis was used to monitor metabolic changes and protease activation close to the PJA after pancreaticoduodenectomy (PD). METHODS: In patients who underwent PD, intraperitoneal metabolites (glycerol, lactate, pyruvate and glucose) were measured by microdialysis, and lactate and glucose in blood were monitored, every 4 h for 5 days, starting at 12.00 hours on the day after surgery. Trypsinogen activation peptide (TAP) was measured in microdialysates as a marker of protease activation. RESULTS: Intraperitoneal glycerol levels and the ratio of lactate to pyruvate were higher after PD and glucose levels were lower in seven patients who later developed symptomatic POPF than in eight patients with other surgical complications (OSC) and 33 with no surgical complications (NSC) (all P < 0·050). TAP was detected at a concentration greater than 0·1 µg/l in six of seven patients with POPF, two of eight with OSC and two of 33 with NSC. Intraperitoneal lactate concentrations were higher than systemic levels in all patients on days 1 to 5 after surgery (P < 0·001). In patients with POPF, high intraperitoneal lactate concentrations were observed without systemic hyperlactataemia. CONCLUSION: Early in the postoperative phase, patients who later developed clinically significant POPF had higher intraperitoneal glycerol concentrations and lactate/pyruvate ratios, and lower glucose concentrations in combination with a TAP level exceeding 0·1 µg/l close to the PJA, than patients who did not develop POPF.

Housing environment influences the need for pain relief during post-operative recovery in mice.

The impact of invasive experimental procedures on perceived stress and pain may be dependent on both physical and social environmental conditions. The aim of this study was to evaluate the effects of a physically and a socially enriched environment on the need for pain relief following painful experimental procedures. A non-invasive method to administer analgesics post-operatively is by means of self-administration which is a feasible objective method to measure perceived pain during the post-operative recovery period. In the present study eight groups of mice housed in different conditions underwent the surgical procedure of caecal manipulation or only exposure to anaesthesia. After surgery the mice were given the choice to self-administer an analgesic available in one of their water bottles during two post-operative weeks. It was shown that socially enriched mice drank i.e. self-administered, less from the analgesic containing water than the non-enriched and socially deprived groups. Mice that underwent operation self-administered more analgesic than mice that received only anaesthesia without operation. The findings indicate that the recovery environment can contribute positively to attenuate the need for pain relief in animals submitted to invasive procedures.

Pancreaticoduodenectomy for peri-ampullary neoplasia leads to specific micronutrient deficiencies.

BACKGROUND/AIMS: After pancreaticoduodenectomy (PD) patients may be deficient in essential micronutrients. This study was designed to determine if this is a consequence of surgery. METHODS: Long-term survivors (>6 months) of PD for peri-ampullary neoplasia and healthy controls (patients' spouse/partner) were enrolled in the study. Specific clinical parameters were recorded, serum micronutrient levels were measured and subjects completed 7-day food diaries. RESULTS: Thirty-seven patients were studied, 25 with paired controls. All were well nourished, as defined by body mass index and food diary analysis. Patients with paired controls were representative of all patients studied. Patients had raised transferrin (median 2.60 vs. 2.16 g/l, p = 0.001) and low ferritin levels (34.9 vs. 119.0 g/l, p < 0.001) indicating relative iron deficiency. Patients also demonstrated lower levels of the anti-oxidants selenium (0.77 vs. 0.93 micromol/l, p < 0.001) and vitamin E (23.2 vs. 35.7 micromol/l, p < 0.001) with 57% of patients having frank selenium deficiencies. Patients had lower levels of vitamin D than controls (15.7 vs. 19.6 micromol/l, p = 0.001) and 30% of patients had a raised parathyroid hormone level, suggesting compensatory mechanisms operate to maintain normocalcaemia. CONCLUSIONS: Long-term survivors of PD are relatively deficient in several micronutrients compared to non-operated controls taking the same diet. We recommend that micronutrient status should be regularly checked in these patients and treated where necessary.

Effect of carbohydrate feeding on insulin action in skeletal muscle after surgical trauma in the rat.

Metabolic stress after surgery is associated with peripheral insulin resistance. Recent studies have suggested that preoperative glucose can ameliorate postoperative decreases in insulin-stimulated glucose disposal. In the present experiments, we used a bowel-resection model of surgical trauma to test the hypothesis that elevations of serum insulin induced by preoperative oral glucose or ad libitum feeding affects postoperative insulin-stimulated glucose uptake in skeletal muscle. Insulin-stimulated glucose transport was measured in vitro in soleus muscles after surgical trauma in fasted rats given oral glucose or water before surgery. Insulin-stimulated glucose transport was also assessed in vitro in fasted or fed traumatized rats and non-traumatized control animals. In addition, stress hormones (glucagon, corticosterone, and adrenaline) were measured before and after surgical trauma in fasted rats and rats fed ad libitum. In vitro skeletal-muscle insulin sensitivity and responsiveness were reduced postoperatively in fasted animals that received oral glucose loads before bowel resections and in rats fed ad libitum or fasted before surgery versus non-traumatized rats (all P < 0.05). Stress-hormone concentrations after trauma did not differ between fed and fasted animals. In the current study, insulin sensitivity and responsiveness were reduced in isolated skeletal muscles after bowel resection, but neither preoperative glucose supplementation nor free intake of mixed nutrients ameliorated the development of postoperative insulin resistance.

Upregulation of uncoupling protein homologues in skeletal muscle but not adipose tissue in posttraumatic insulin resistance.

Metabolic alterations after surgical stress include peripheral insulin resistance and increased utilization of fat as a fuel substrate. An up-regulation of skeletal muscle uncoupling proteins (UCPs) has been associated with physiologic states of insulin resistance and enhanced fat metabolism in rodents. We examined whether posttraumatic insulin resistance induced the UCPs in gastrocnemius and soleus muscle and white adipose tissue in an experimental model of surgical trauma. Insulin sensitivity was significantly reduced in isolated soleus muscles but unchanged in adipocytes after trauma. In traumatized rats, mRNA and protein contents of UCP2 and UCP3 and were significantly increased in both muscle types. UCP2 protein content in adipose tissue was unaltered by surgical stress. Circulating NEFAs and glycerol were reduced after surgical trauma. We hypothesize that the changes in UCP2 and UCP3 gene and protein expression are involved in the regulation of substrate utilization in posttraumatic insulin resistance.

Preoperative feeding does not reverse postoperative insulin resistance in skeletal muscle in the rat.

Metabolic studies on injured and postoperative patients have shown impaired glucose disposal in peripheral tissues after trauma. Using small-bowel resection as a model of surgical trauma, we investigated whether substrate availability could ameliorate the changes in muscle glucose uptake induced by trauma. We also studied the effect of preoperative feeding on postoperative insulin-stimulated insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol (PI) 3-kinase activity in both Wistar rats and genetically non-insulin-dependent diabetic Goto-Kakazaki rats (GK rats). Serum glucose, insulin, plasma epinephrine, lactate, and plasma nonesterified free fatty acids (NEFAs) were measured as indicators of the metabolic state and surgical stress. Insulin-stimulated glucose transport was significantly reduced in fed traumatized Wistar rats compared with fed nontraumatized rats (P < .05). Significant increases in in vivo insulin-stimulated IRS-1-associated PI 3-kinase activity were found in fed traumatized Wistar rats compared with fed nontraumatized Wistar rats and fasted traumatized Wistar rats, as well as fed traumatized GK rats compared with fed nontraumatized GK animals (all P < .017). Serum insulin concentrations were significantly reduced in fed traumatized Wistar and GK rats compared with the respective fed nontraumatized groups (both P < .01). Serum glucose levels were significantly elevated in fed traumatized GK rats compared with fed nontraumatized animals (P < .01). In the present study, preoperative feeding did not prevent a postoperative reduction in insulin-stimulated glucose transport in skeletal muscle. The finding that insulin-stimulated PI 3-kinase activity increased after trauma in both Wistar and GK rats indicates that postoperative insulin resistance is not caused by an impairment in the early steps of the insulin signaling pathway. The postoperative decreases in serum insulin despite high blood glucose suggest that trauma impairs the insulin response to hyperglycemia.

The intracellular mechanism of insulin resistance in pancreatic cancer patients.

The diabetes that frequently occurs in pancreatic cancer patients is characterized by profound peripheral insulin resistance. The intracellular mechanism of this insulin resistance was investigated in skeletal muscle biopsies from pancreatic cancer patients with or without diabetes and control subjects. Insulin receptor (IR) binding, tyrosine kinase activity, IR messenger RNA (mRNA), IR substrate-1 content, GLUT-4, and GLUT-4 mRNA content were all normal in pancreatic cancer patients. In contrast, multiple defects in glycogen synthesis were found in pancreatic cancer patients, especially in those with diabetes. Glycogen synthase I activity, total activity, and mRNA levels were significantly decreased in pancreatic cancer patients compared with controls. The fractional velocity of glycogen synthase was decreased only in the diabetic pancreatic cancer group. Glycogen phosphorylase a and b activities were increased in diabetic pancreatic cancer patients, but glycogen phosphorylase mRNA levels were not significantly different. The insulin resistance associated with pancreatic cancer is associated with a post-IR defect, which impairs skeletal muscle glycogen synthesis and glycogen storage.

Effects of long-term infusion of anorexic concentrations of islet amyloid polypeptide on neurotransmitters and neuropeptides in rat brain.

Islet amyloid polypeptide (IAPP or amylin) potently reduces food intake in rats at or near physiological concentrations. Although the mechanisms of action of IAPP are not understood, the brain is a suggested site. Changes in hypothalamic and striatal neurotransmission have been reported following acute systemic administration of a pharmacological concentration of IAPP. In the current study, we evaluated the effects of chronic administration of low doses of IAPP on satiety-related neurotransmitters and neuropeptides in the hypothalamus, hippocampus, striatum, left cortex, and right cortex of the rat. Doses of 0, 5 and 25 pmol IAPP/kg-min were administered subcutaneously for 2 or 5 days. Food intake was reduced by 27 and 44% (both P<0.001) for the 5 and 25 pmol/kg-min groups, respectively, in the 2-day experiment and was decreased by 14% (P<0.01) and 24% (P<0.001), respectively, in the 5-day experiment. Body weight was significantly decreased in a dose-dependent fashion. In the 2-day experiment, norepinephrine increased in the hypothalamus in the 5 pmol IAPP/kg-min group, and neurotensin increased in the hippocampus in the 25 pmol/kg-min rats (both P<0.05). In the 5-day, 5 pmol/kg-min rats, 5-hydroxyindoleacetic acid (5-HIAA) increased in the hypothalmus and cholecystokinin (CCK) increased in the striatum (both P<0.05). In the 5-day, 25 pmol/kg-min group, neuropeptide Y (NPY) increased in the hypothalamus (P<0.01) and CCK increased in the hypothalmus and striatum (both P<0.05). The present study confirms that IAPP is a potent anorectic peptide at low doses and suggests that IAPP not only affects classical neurotransmitters in the brain but also alters concentrations of neuropeptides known to be involved in food intake.

Skeletal muscle insulin resistance after trauma: insulin signaling and glucose transport.

Surgical trauma induces peripheral insulin resistance; however, the cellular mechanism has not been fully elucidated. We examined the effects of surgical trauma on insulin receptor signaling and glucose transport in skeletal muscle, a tissue that plays a predominant role in maintaining glucose homeostasis. Surgical trauma was induced by intestinal resection in the rat. Receptor phosphorylation was not altered with surgical trauma. Phosphotyrosine-associated phosphatidylinositol (PI) 3-kinase association was increased by 60 and 82% compared with fasted and fed controls, respectively (P < 0. 05). Similar results were observed for insulin receptor substrate-1-associated PI 3-kinase activity. Insulin-stimulated protein kinase B (Akt kinase) phosphorylation was increased by 2.2-fold after surgical trauma (P < 0.05). The hyperphosphorylation of Akt is likely to reflect amplification of PI 3-kinase after insulin stimulation. Submaximal rates of insulin-stimulated 3-O-methylglucose transport were reduced in trauma vs. fasted rats by 51 and 38% for 100 and 200 microU/ml of insulin, respectively (P < 0.05). In conclusion, insulin resistance in skeletal muscle after surgical trauma is associated with reduced glucose transport but not with impaired insulin signaling to PI 3-kinase or its downstream target, Akt. The surgical trauma model presented in this report provides a useful tool to further elucidate the molecular mechanism(s) underlying the development of insulin resistance after surgical trauma.

Lipolysis in human fat cells obtained under local and general anesthesia.

OBJECTIVES: As adipose tissue is usually obtained during local or general anesthesia in clinical studies, these two forms of anesthesia were presently compared as regards lipolysis induced by catecholamines in isolated human fat cells. DESIGN: Fat samples from the abdominal subcutaneous region were obtained first during local anesthesia (lidocaine) given so that the anesthetic agent did not influence lipolysis and second, during gastric banding under general anesthesia (propofol) immediately after skin incision. SUBJECTS: Eleven obese patients, drug free and otherwise healthy. MEASUREMENTS: Isolated fat cells were incubated in the presence or absence of increasing concentrations of different lipolysis agents, acting at adrenoceptor or various post-receptor levels in the lipolytic cascade. Glycerol release to the incubation medium was measured as an index of lipolysis. RESULTS: All agonists caused a concentration dependent increase (terbutaline, dobutamine, CGP 12177, forskolin, dibutyryl cyclic AMP, isoprenaline and noradrenaline) or inhibition (clonidine) of glycerol release. The comparison of data from local and general anesthesia procedures showed no statistical difference in glycerol response for any of the drugs used. CONCLUSIONS: Adrenergic regulation of lipolysis is not influenced by the mode of sampling, at least not in subcutaneous fat cells of obese subjects obtained during local anesthesia with lidocaine as compared to general anesthesia with propofol.