Towards precision dosing of vancomycin in critically ill patients: an evaluation of the predictive performance of pharmacometric models in ICU patients.

OBJECTIVES: Vancomycin dose recommendations depend on population pharmacokinetic models. These models have not been adequately assessed in critically ill patients, who exhibit large pharmacokinetic variability. This study evaluated model predictive performance in intensive care unit (ICU) patients and identified factors influencing model performance. METHODS: Retrospective data from ICU adult patients administered vancomycin were used to evaluate model performance to predict serum concentrations a priori (no observed concentrations included) or with Bayesian forecasting (using concentration data). Predictive performance was determined using relative bias (rBias, bias) and relative root mean squared error (rRMSE, precision). Models were considered clinically acceptable if rBias was between ±20% and 95% confidence intervals included zero. Models were compared with rRMSE; no threshold was used. The influence of clinical factors on model performance was assessed with multiple linear regression. RESULTS: Data from 82 patients were used to evaluate 12 vancomycin models. The Goti model was the only clinically acceptable model with both a priori (rBias 3.4%) and Bayesian forecasting (rBias 1.5%) approaches. Bayesian forecasting was superior to a priori prediction, improving with the use of more recent concentrations. Four models were clinically acceptable with Bayesian forecasting. Renal replacement therapy status (p < 0.001) and sex (p = 0.007) significantly influenced the performance of the Goti model. CONCLUSIONS: The Goti, Llopis and Roberts models are clinically appropriate to inform vancomycin dosing in critically ill patients. Implementing the Goti model in dose prediction software could streamline dosing across both ICU and non-ICU patients, considering it is also the most accurate model in non-ICU patients.

Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

Vitamin D status and supplementation in adult patients receiving extracorporeal membrane oxygenation.

The prevalence of vitamin D deficiency in critical illness is known to be high and associated with adverse clinical outcomes. Patients receiving extracorporeal membrane oxygenation (ECMO) may be at increased risk of vitamin D deficiency due to high severity of acute illness. Challenges with drug dosing in ECMO patients are recognised due to increased volume of distribution and drug absorption to circuit components. To describe the prevalence of vitamin D deficiency in ECMO patients and the effect of intramuscular dosing of cholecalciferol on levels of vitamin D metabolites, and to compare these data with intensive care unit (ICU) patients not receiving ECMO, two prospective studies were performed sequentially: an observational study of 100 consecutive ICU patients and an interventional study assessing effects of intramuscular cholecalciferol in 50 ICU patients. The subgroup of patients who required ECMO support in each of these studies was analysed and compared to patients who did not receive ECMO. Twenty-four ECMO patients, 12 from the observational study and 12 from the interventional study (who received intramuscular cholecalciferol) were studied-21/24 (88%) ECMO patients were vitamin D deficient at baseline compared to 65/126 (52%) of non-ECMO patients (P=0.006). Of the 12 ECMO patients who received cholecalciferol, six patients (50%) achieved correction of deficiency compared to 36/38 (95%) non-ECMO patients (P=0.001). The prevalence of vitamin D deficiency is higher in ECMO patients compared to other critically ill adults. Correction of deficiency with single dose cholecalciferol is not reliable; higher or repeated doses should be considered to correct deficiency.

Current limitations of the assessment of haemostasis in adult extracorporeal membrane oxygenation patients and the role of point-of-care testing.

Haemostatic perturbations are commonly seen in extracorporeal membrane oxygenation (ECMO) patients and remain a clinical challenge, contributing significantly to morbidity and mortality. The approach to anticoagulation monitoring and the management of bleeding varies considerably across ECMO centres. Routine laboratory tests have their limitations in terms of turnaround time and specificity of information provided. Newer point-of-care testing (POCT) for coagulation may overcome these issues, as it provides information about the entire coagulation pathway from clot initiation to lysis. It is also possible to obtain qualitative information on platelet function from these tests. Furthermore, the ability to incorporate these results into a goal-directed algorithm to manage bleeding with targeted transfusion strategies appears particularly attractive and cost effective. Further studies are required to evaluate the utility of POCT to optimise bleeding and anticoagulation management in these complex patients.

Bilateral thoracoscopic splanchnicectomy for pain in patients with chronic pancreatitis impairs adrenomedullary but not noradrenergic sympathetic function.

BACKGROUND: Bilateral thoracoscopic splanchnicectomy (BTS) is a well-known technique to alleviate intractable pain in patients with chronic pancreatitis. BTS not only disrupts afferent fibers from the pancreas that mediate pain but also postganglionic sympathetic fibers, which originate in segments T5-T12 and which innervate the vasculature of the liver, pancreas, and the adrenal gland. The purpose of this study was to assess whether and how BTS affects sympathetic noradrenergic and adrenomedullary function in patients with chronic pancreatitis. METHODS: Sixteen patients with chronic pancreatitis for at least 1 year underwent autonomic function testing before and 6 weeks after BTS for intractable pain. Testing was performed during supine rest and during sympathetic stimulation when standing. RESULTS: Supine and standing systolic and diastolic blood pressure were significantly lower post-BTS compared with pre-BTS (P = 0.001). One patient showed orthostatic hypotension after BTS. Baseline plasma norepinephrine levels and plasma norepinephrine responses to sympathetic activation during standing were not reduced by BTS. In contrast, supine plasma epinephrine levels and responses during standing were significantly reduced (P < 0.001). Parasympathetic activity was unaffected by BTS as shown by unaltered Valsalva ratio, I-E difference, and ΔHRmax. CONCLUSIONS: BTS for pain relief in patients with chronic pancreatitis reduced adrenomedullary function, due to disruption of the efferent sympathetic fibers to the adrenal gland. BTS did not affect noradrenergic sympathetic activity, although blood pressure was lower after the sympathectomy.

Increased sympathetic activity in chronic pancreatitis patients is associated with hyperalgesia.

Pain treatment in chronic pancreatitis patients is difficult, with pain frequently relapsing or persisting. Recent studies suggest that altered central nervous system pain processing underlies the chronic pain state in these patients. There is evidence that increased sympathetic activity may also play a role in some chronic pain syndromes. This study assessed sympathetic nervous system activity and its relation to pain processing in patients with severe painful chronic pancreatitis. The authors postulated that chronic pancreatitis patients with more sympathetic activity exhibit more generalized hyperalgesia. In 16 chronic pancreatitis patients, sympathetic activity was measured via venous plasma norepinephrine (NE) levels (supine, standing). Pain processing was quantified via pressure pain tolerance thresholds (PPTs) in dermatomes T10 (pancreatic area), C5, T4, L1. Five patients showed increased supine plasma NE levels (NE ≥ 3.0 nmol/L). PPTs were lower in patients with increased NE levels (INE) compared with patients with normal NE (NNE) (means [95% confidence interval]: INE 402 kPa [286-517] versus NNE 522 kPa [444-600]; P = .042). In severe chronic pancreatitis patients, increased sympathetic activity and hyperalgesia appear associated, suggesting that sympathetic activity may also play a role in these patients' pain.

Checking concordance between findings and diagnoses in sonographic reports by a knowledge-based documentation system.

PURPOSE: Sonographic reports are examiner-dependent and may not always be reliable. We investigated concordance between documented findings and diagnostic conclusions--not the objective correctness of both--with the help of a knowledge-based documentation system. MATERIALS AND METHODS: The knowledge-based documentation system SonoConsult (SC) is routinely used in the ultrasound unit of a gastroenterological clinic for more than four years. Physicians documented findings with goal directed questionnaires, and diagnostic conclusions with free text. The consistency of documented findings and diagnoses was checked with the help of SC in a two-step process: 1. the diagnoses inferred by SC based on the documented findings were compared to the diagnoses of the physicians stated as free text. 2. In case of discrepancies, a more thorough comparison was performed manually by the medical authors of this study. For judging the practical relevance of discrepancies, diagnostic codes were pre-classified as a) being presumably of higher and lower relevance for the clinician and b) requiring simple or complex inference rules from the findings. RESULTS: In a first series of 250 consecutive cases with 934 diagnoses (3.7 diagnoses per case), 71.1% showed agreement between diagnoses of the physicians and of SC and were judged as consistent compared to the documented findings. 24.4% of the diagnoses suggested by the documented findings, however, were not mentioned by the physicians (false negative) and 4.5% were mentioned by the physicians but not suggested by the documented findings (false positive). From the 24.4% missing diagnoses, 40% were pre-classified as being of higher relevance for the clinician. In a second series of 161 consecutive cases with 501 diagnoses (3.1 diagnoses per case), 61.1% were judged as consistent compared to the documented findings, 36.1% false negative and 2.8% false positive. In this study, we differentiated the missing diagnoses due to their inferential complexity: From the 152 complex diagnoses, 44% were missing, while from the 349 simple diagnoses, 32.7% were missing. CONCLUSION: As shown for a sonographic department of a clinic of internal medicine, in sonographic reports, one has to be aware of discrepancies between question-set-based documentations of findings and diagnostic conclusions of the examiners. While a detailed documentation of findings is the basis of quality control, consistency checks between documented findings and diagnostic conclusions, which might be done automatically in an electronic patient record, would considerably improve the quality of the reports.

Effect of thoracoscopic splanchnic denervation on pain processing in chronic pancreatitis patients.

BACKGROUND: Central sensitisation due to visceral pancreatic nociceptive input may play an important role in chronic pancreatitis pain. Using quantitative sensory testing (QST), this first study investigates whether thoracoscopic splanchnic denervation (TSD), performed to reduce nociceptive visceral input, affects central sensitisation in chronic pancreatitis patients. PATIENTS AND METHODS: We studied 19 chronic pancreatitis patients (11 men, 8 women on stable opioid medication) and 18 healthy volunteers as preoperative controls. Preoperatively and 6 weeks after TSD, pain numeric rating scores, opioid medication, and thresholds to electric skin stimulation and pressure pain (measured in dermatomes T10 (pancreas), C5, T4, L1, L4) were documented. Treatment success was defined as cessation of opioids 6 weeks after TSD. RESULTS: Six weeks after TSD, there was a trend towards lower pain scores, only 10 patients were still on opioids (P<0.05 vs. preoperatively) and thresholds overall were significantly higher than preoperatively (pressure pain: +25%, P<0.001; electric: sensation +55%, pain detection +34%, pain tolerance +21%, P<0.05). Gender-specific differences in hypoalgesia patterns were seen. Preoperatively, TSD treatment successes consumed significantly less opioids than failures, without significant differences in preoperative patterns of neuroplasticity. CONCLUSIONS: TSD for chronic pancreatitis pain resulted in fewer patients on opioids and overall increases in pain thresholds. Our results suggest that TSD for reducing visceral nociceptive input may be effective in reducing resulting central sensitisation. Although patients benefiting from TSD consume less opioids preoperatively, we were unable to clearly link treatment success with specific perioperative patterns of neuroplasticity such as the presence or absence of hyperalgesia.

Assessment of diaphragmatic function with cervical magnetic stimulation in critically ill patients.

The objective of this study was to evaluate a non-volitional measurement to assess diaphragmatic function in intubated and mechanically ventilated patients in a prospective pilot interventional clinical trial. The study was conducted in an 18-bed postoperative intensive care unit based at a university hospital. Patients were prospectively assigned to two groups. Group 1 consisted of eight patients with ventilator weaning failure. Group 2 consisted of eight intubated and ventilated patients who were studied shortly after major surgery and were successfully extubated there-after The twitch pressure response after cervical magnetic stimulation of the phrenic nerves was measured at the endotracheal tube at different PEEP levels. In group 2 the twitch transdiaphragmatic pressure, defined as the difference between twitch gastric and twitch oesophageal pressure was also evaluated. In group 1 the mean twitch pressure at the endotracheal tube on PEEP 0, 5 and 10 cmH2O was 5.2, 4.5 and 2.6 cmH2O: In group 2 this was significantly higher (15.1 cmH2O on PEEP 0 and 12.2 cmH2O on PEEP 5). A good correlation was found between twitch diaphragmatic pressure and twitch pressure at the endotracheal tube (r2 = 0.96) and between twitch oesophageal pressure and twitch pressure at the endotracheal tube (r2 = 0.98). Patients with weaning failure have significantly lower twitch pressure at the endotracheal tube suggesting diaphragmatic dysfunction. Twitch pressure at the endotracheal tube may be a useful parameter to screen for diaphragmatic dysfunction in intubated critically ill patients. Further studies are needed to confirm these preliminary findings.

HepatoConsult: a knowledge-based second opinion and documentation system.

HepatoConsult is a publicly available knowledge-based second opinion and documentation system aiding in the diagnosis of liver diseases. The positive results of a prospective diagnostic evaluation study encouraged its use in clinical routine, although the available hardware infrastructure was not optimal. The comments of the physicians who used the system confirmed the results of the study and showed that the time for data entering is acceptable and the implicit standardization of terminology and documentation is welcome. Suggestions for improvement included the interface to enter data more easily, the scope to be usable for more patients and the additional capability to generate medical reports from the data.

Long-term results of bilateral thoracoscopic splanchnicectomy in patients with chronic pancreatitis.

BACKGROUND: The management of pain in patients with chronic pancreatitis is difficult. The aim of this prospective study was to evaluate the early and long-term pain relief provided by bilateral thoracoscopic splanchnicectomy. METHODS: From August 1995 to August 1999, 44 patients with chronic pancreatitis underwent bilateral thoracoscopic splanchnicectomy. Data were collected prospectively. Thirty-six patients required opioids. Pain intensity was registered before operation and at regular intervals after surgery by means of a visual analogue scale (VAS). Use of analgesics (opioids; non-steroidal anti-inflammatory drugs and acetaminophen; no analgesics or aminocetophen) was noted before and after splanchnicectomy. Median follow-up was 36 (range 12-60) months. RESULTS: The procedure was technically successful in 40 patients. Thirty-six patients had no complications. Eleven of 24 patients who have been followed up for 24 months or more had a significantly reduced VAS score at 2 years (median (range) 8.5 (7-10) versus 2.5 (0-5); P < 0.01). The cumulative rate of pain relief was 46 per cent 48 months after splanchnicectomy. CONCLUSION: Bilateral thoracoscopic splanchnicectomy alleviated pain in patients with chronic pancreatitis. It was associated with a low morbidity rate and no deaths. Pain eventually recurred in approximately 50 per cent.

Neuromuscular effects of rapacuronium on the diaphragm and skeletal muscles in anaesthetized patients using cervical magnetic stimulation for stimulating the phrenic nerves.

BACKGROUND AND OBJECTIVE: Non-depolarizing neuromuscular blocking agents have a shorter duration of action on the diaphragm than on skeletal muscles. It was to be tested if this also held true for rapacuronium, a short-acting, amidosteroid non-depolarizing neuromuscular blocker, lately withdrawn from the market, using a novel technique for stimulating the diaphragm and assessing its function. METHODS: Anaesthesia was induced with propofol 2 mg kg(-1) and remifentanil 1 microg kg(-1), and the trachea was intubated after topical anaesthesia. Rapacuronium was given at a dose of 1.5 mg kg(-1). The diaphragm was stimulated by cervical magnetic stimulation of the phrenic nerves (2 Tesla, single coil) and airway pressure responses were measured at the endotracheal tube connector. The neuromuscular effects at the adductor pollicis and orbicularis oculi muscles were measured by acceleromyography. RESULTS: Fifteen males and five females (ASA I and II; 27 +/- 8 yr; 73 +/- 13kg; mean +/- SD) were recruited. Median maximal relaxation was less (P < 0.01) for the diaphragm (89%) than for the adductor pollicis or orbicularis oculi muscles (each 100%). The time to 25% recovery was shorter for the diaphragm than for adductor pollicis or orbicularis oculi (7.5 +/- 3.1 versus 14.1 +/- 3.7 and 15.1 +/- 3.5 min, respectively, P < 0.01). Recovery from 25 to 75% was identical for the diaphragm and adductor pollicis (9.4 +/- 2.9 versus 9.1 +/- 3.5 min), but longer for orbicularis oculi (13.4 +/- 4.2 min, P < 0.01). The median recovery time to TOF0.8 was shorter for the diaphragm (23.9 min) than for the adductor pollicis or orbicularis oculi muscles (31.5 and 28.4 min, respectively; P < 0.05). CONCLUSIONS: As with other non-depolarizing muscle relaxants, the duration of the clinical effect of rapacuronium was shorter for the diaphragm than for skeletal muscle. The recovery index was identical for the diaphragm and adductor pollicis.

Comparison of ventilatory and haemodynamic effects of BIPAP and S-IMV/PSV for postoperative short-term ventilation in patients after coronary artery bypass grafting.

The aim of the present multiple cross-over study was to compare the effects of biphasic positive airway pressure (BIPAP) ventilation with synchronized intermittent mandatory ventilation combined with pressure support ventilation (S-IMV/PSV) in sedated and awake patients after coronary artery bypass grafting (CABG) surgery. Twenty-four patients with no evidence of preoperative respiratory dysfunction and an uncomplicated intraoperative course were investigated. The patients were randomly assigned to one of two groups starting with either BIPAP or S-IMV/PSV mode. Haemodynamic measurements and blood gas analyses were performed during sedation with 2.0 mg kg(-1) h(-1) propofol in the primary mode, after switching to the alternative ventilatory mode, and in the primary mode again. The same sequence of measurements was repeated in awake patients who had reached extubation criteria. In awake patients, PSV was performed instead of S-IMV. Statistical analysis of data was performed using non-parametric tests. Inspiratory peak pressure increased significantly during S-IMV/PSV in sedated patients in both groups. Other ventilatory parameters did not differ significantly between BIPAP and S-IMV/PSV in both groups. Similarly, haemodynamic parameters and blood-gas analyses did not vary with the ventilatory mode. Our results demonstrate that BIPAP ventilation has comparable effects on haemodynamics and pulmonary gas exchange compared with S-IMV/PSV and PSV when used for short-term ventilatory support in patients after cardiac surgery.

Pressure signal transmission of five commercially available oesophageal balloon catheters.

OBJECTIVE: Five commercially available oesophageal balloon catheters (OBCs) were tested to evaluate the accuracy in transmitting fast-changing pressure signals which can be observed, for example, during phrenic nerve stimulation. SETTING: Research laboratory of a university hospital. METHOD: The OBCs tested varied in length (900-1390 mm) and inner diameter (0.9-1.5 mm) as well as in balloon material [latex or polyvinylchloride (PVC)]. A 180-cm tube served as a control. A sudden pressure drop was generated by the explosion of a pressurized latex balloon. The time between the pressure drop and 75, 50, 25 and 10% of the maximal pressure was measured. RESULTS: The time intervals required to transduce a pressure drop of 90% varied between the different OBCs from 85 to 476 ms (control 32 ms). Transmission time was lower in OBCs with a larger inner diameter. Shortening the OBCs resulted in a further decrease in transmission time. CONCLUSION: The type of OBC used has an impact on signal processing. An OBCs with a short transmission time should be chosen, especially if fast pressure changes are to be evaluated such as during phrenic nerve stimulation.

Hyperhomocysteinemia as a cause of superior vena cava syndrome.

A case is presented in which superior vena cava (SVC) syndrome was caused by a stenosis of the SVC due to thrombosis. Hyperhomocysteinemia was diagnosed as a possible underlying mechanism. The role of hyperhomocysteinemia as a risk factor for the development of recurrent venous thrombosis, its diagnosis, and treatment are discussed.

Bilateral thoracoscopic splanchnicectomy in patients with chronic pancreatitis.

BACKGROUND: Intractable pain, the most prominent feature of chronic pancreatitis, causes the patient great disability, and its treatment poses a difficult problem for gastroenterologist and surgeon alike. The main goal of treatment is to provide sufficient and lasting pain relief without the use of opiates. Conservative management, including stopping alcohol consumption, dietary measures, pancreatic enzyme suppletion and analgesics, is discussed. When these measures fail, surgery is often unavoidable. Indications, effect on pain relief, morbidity and mortality of drainage and resection procedures are described. Bilateral thoracoscopic splanchnicectomy, a newly developed operation to alleviate pain irrespective of the type of anatomic abnormality, is outlined in more detail. Early encouraging results of pain relief in patients with chronic pancreatitis after thoracoscopic splanchnicectomy are presented.

[The evaluation of HepatoConsult, a hepatological expert system--the initial results and trends]. / Evaluation von HepatoConsult, einem hepatologischen Expertensystem--erste Ergebnisse und Trends.

BACKGROUND AND OBJECTIVE: HepatoConsult (HC) is a medical expert system, based on the expert system building block D3, designed to aid in the diagnosis of liver and biliary tract disease. It was the aim of this study to evaluate its diagnostic competence in clinical cases prospectively. PATIENTS AND METHODS: The diagnostic accuracy of HC was tested prospectively in 106 consecutive patients with the main diagnosis of liver disease. 57 were ambulant, 49 were in-patients. The data were obtained and stored at defined phases of the diagnosis. The diagnoses put forward by HC were compared with the final clinical diagnosis and, on the basis of the data, checked for plausibility by four experienced physicians. RESULTS: After history taking and physical examination HC put forward the main diagnosis, as established by the doctors in charge, in 60% of patients. After addition of the results of basic laboratory tests and sonography, HC provided the correct diagnosis in 85% and, after inclusion of all the findings, in 93%. In almost all cases HC put forward diagnoses that were, on the basis of the supplied data, considered correct by the four physicians experienced in liver disease. In 56% of cases HC provided more differentiated diagnoses or items in the differential diagnosis than the attending doctors. In the opinion of the four assessors HC had not put forward any seriously wrong diagnoses. CONCLUSION: HC can be useful in solving diagnostic problems and thus in ensuring the quality of medical diagnoses.

Beta-cell function of the pancreas after necrotizing pancreatitis.

AIM: To investigate the late sequellae of necrotizing pancreatitis on the endocrine function of the pancreas. PATIENTS AND METHODS: Twenty patients, 15 men (mean +/- SEM age 52.2+/-2.6 years and BMI 26.8+/-0.8 kg/m2) and 5 women (age 51.0+/-7.6 years and BMI 26.7+/-0.8 kg/m2) were submitted to a glucagon stimulation test 63 (range 8-136) months after an attack of pancreatitis. All nondiabetic patients (n = 15) were also submitted to an oral glucose tolerance test. For comparison, 16 healthy volunteers, 8 men (age 56.0+/-0.9 years and BMI 26.3+/-0.4 kg/m2) and 8 women (age 50.5+/-1.0 years and BMI 28.2+/-0.6 kg/m2), were also studied. RESULTS: Five patients (25%) had diabetes mellitus and needed insulin treatment, 6 patients (30%) had an impaired glucose tolerance (IGT). Nondiabetic patients (IGT included) had a significantly higher basal insulin level (15.8+/-1.9 vs. 10.9 +/-2.2 mU/l, p < 0.05) and a lower glucose/insulin ratio (p < 0.05) compared with controls. The serum concentrations of insulin and C peptide, after stimulation with glucagon, calculated as peak value, maximal increment and as area under the curve were not significantly different in the nondiabetic patients compared to controls. The subgroup of IGT patients had a significantly higher basal C peptide (p < 0.05) and a reduced maximal increment (p < 0.05). CONCLUSIONS: After nonresectional therapy for necrotizing pancreatitis, there is a high prevalence of disturbances in glucose metabolism. Patients with IGT have signs of both loss of beta-cell function and insulin resistance.