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In this open-label multicentre randomised controlled trial, we investigated three peri-operative treatment strategies to lower glucose and reduce the need for rescue insulin in patients aged 18-75 years with type-2 diabetes mellitus undergoing non-cardiac surgery. Patients were randomly allocated using a web-based randomisation program to premedication with liraglutide (liraglutide group), glucose-insulin-potassium infusion (insulin infusion group) or insulin bolus regimen (insulin bolus group), targeting a glucose < 8.0 mmol.l -1 . The primary outcome was the between group difference in median glucose levels 1 h after surgery. We analysed 150 patients (liraglutide group n = 44, insulin infusion group n = 53, insulin bolus group n = 53) according to the intention-to-treat principle. Median (IQR [range]) plasma glucose 1 h postoperatively was lower in the liraglutide group compared with the insulin infusion and insulin bolus groups (6.6 (5.6-7.7 [4.2-13.5]) mmol.l -1 vs. 7.5 (6.4-8.3 [3.9-16.6]) mmol.l -1 (p = 0.026) and 7.6 (6.4-8.9 [4.7-13.2]) mmol.l -1 ) p = 0.006, respectively). The incidence of hypoglycaemia and postoperative complications did not differ between the groups. Six patients had pre-operative nausea in the liraglutide group, of which two had severe nausea, compared with no patients in the insulin infusion and insulin bolus groups (p = 0.007). The pre-operative administration of liraglutide stabilised peri-operative plasma glucose levels and reduced peri-operative insulin requirements, at the expense of increased pre-operative nausea rates., (© 2017 The Association of Anaesthetists of Great Britain and Ireland.)

Background: Perioperative hyperglycemia is associated with postoperative complications after major surgery. However, more than 50% of surgical procedures are performed in an ambulatory setting, where glucose is not routinely measured. The objectives of this study were to investigate the change in capillary glucose during ambulatory surgery, to identify patients at risk for perioperative increasing glucose and to evaluate whether hyperglycemia predisposes for complications after ambulatory surgery., Methods: In this prospective multicenter cohort study, adult patients planned for ambulatory surgery, were included and capillary glucose was measured 1 hour before and 1 hour after surgery. Patients were contacted 90 days after surgery to determine the occurrence of postoperative complications., Results: Nine hundred and nine patients were included, 48 (5.3%) patients had diabetes mellitus (DM). Overall median glucose increased from 5.4 mmol L-1 preoperatively to 5.6 mmol L-1 postoperatively (P<0.001). Hyperglycemia, glucose ≥7.8 mmol L-1, occurred in 8.8% of the patients. Dexamethasone administration (given in 406 [44.7%] patients) was a risk factor for glucose increase (P<0.001). Hyperglycemia was not a risk factor for postoperative complications (OR 1.19, 95%CI 0.57-2.48, P=0.646). However, prediagnosed DM was a risk factor for postoperative complications, independent of hyperglycemia (OR 2.56, 95%CI 1.10-5.97, P=0.030)., Conclusion: Minor ambulatory surgery is not associated with a clinically relevant increase in glucose. The very small glucose increase we observed could be attributed to the administration of dexamethasone for PONV prophylaxis. Hyperglycemia during ambulatory surgery is not associated with complications after discharge.

Background: Diabetes mellitus (DM) is associated with poor outcome after surgery. The prevalence of DM in hospitalised patients is up to 40%, meaning that the anaesthesiologist will encounter a patient with DM in the operating room on a daily basis. Despite an abundance of published glucose lowering protocols and the known negative outcomes associated with perioperative hyperglycaemia in DM, there is no evidence regarding the optimal intraoperative glucose lowering treatment. In addition, protocol adherence is usually low and protocol targets are not simply met. Recently, incretins have been introduced to lower blood glucose. The main hormone of the incretin system is glucagon-like peptide-1 (GLP-1). GLP-1 increases insulin and decreases glucagon secretion in a glucose-dependent manner, resulting in glucose lowering action with a low incidence of hypoglycaemia. We set out to determine the optimal intraoperative treatment algorithm to lower glucose in patients with DM type 2 undergoing non-cardiac surgery, comparing intraoperative glucose-insulin-potassium infusion (GIK), insulin bolus regimen (BR) and GPL-1 (liragludite, LG) treatment., Methods/design: This is a multicentre randomised open label trial in patients with DM type 2 undergoing non-cardiac surgery. Patients are randomly assigned to one of three study arms; intraoperative glucose-insulin-potassium infusion (GIK), intraoperative sliding-scale insulin boluses (BR) or GPL-1 pre-treatment with liraglutide (LG). Capillary glucose will be measured every hour. If necessary, in all study arms glucose will be adjusted with an intravenous bolus of insulin. Researchers, care givers and patients will not be blinded for the assigned treatment. The main outcome measure is the difference in median glucose between the three study arms at 1 hour postoperatively. We will include 315 patients, which gives us a 90% power to detect a 1 mmol l(-1) difference in glucose between the study arms., Discussion: The PILGRIM trial started in January 2014 and will provide relevant information on the perioperative use of GLP-1 agonists and the optimal intraoperative treatment algorithm in patients with diabetes mellitus type 2., Trial Registration: ClinicalTrials.gov, NCT02036372.

On the initiative of the Dutch Association of Anaesthesiologists, a multidisciplinary workgroup has revised the 2003 practice guideline on 'Postoperative pain treatment' for adults and children. The main reason for revision was the availability of new drugs and new methods of administration. The most important deviations from the previous edition are the following. The organisation of care has been amended according to the current themes of the Safety Management System in the Netherlands, and a prediction model for postoperative pain was added. The drugs oxycodone, S-ketamine, pregabalin, gabapentin and metamizole were added, as well as new methods of administration and techniques for preventing postoperative pain. This revised guideline is more conservative than the previous one in the choice of epidural analgesia. In patients with relative contraindications for epidural analgesia, peripheral and locoregional blocks or multimodal pain treatment are advised. In the case of postoperative nausea and vomiting, administration of dexamethasone, droperidol and 5-HT3-antagonists is recommended, preferably in combination. Non-medicinal treatment options are not recommended.

Purpose: Anastomotic leakage is a serious complication after colorectal surgery. Pre- and intraoperative factors may contribute to failure of colorectal anastomosis. In this study we have tried to determine risk factors for anastomotic leakage, with special emphasis on intraoperative blood pressure changes., Methods: During a 24-month period, patients receiving a colorectal anastomosis were prospectively evaluated. For each patient preoperative characteristics, intraoperative adverse events and surgical outcome data were collected. Blood pressure changes were calculated as a relative decrease (>25% and >40%) from preoperative baseline values., Results: During the study period, 285 patients underwent colorectal surgery with an anastomosis. Fifteen patients developed an anastomotic leakage (5.3%). All patients who developed a leakage had a left-sided procedure (P < 0.001). When blood loss was more than 250 mL (P = 0.003) or an intraoperative adverse event occurred (P = 0.050), the risk for developing an anastomotic leakage was significantly increased. A preoperative high diastolic blood pressure of ≥90 mmHg (P = 0.008) and severe intraoperative hypotension [>40% decrease in diastolic blood pressure (P = 0.049)] were identified as univariate risk factors for anastomotic leakage., Conclusions: The development of an anastomotic leakage after colorectal surgery is related to surgical, patient and anaesthetic risk factors. A high preoperative diastolic blood pressure and profound intraoperative hypotension combined with complex surgery, marked by a blood loss of ≥250 mL and the occurrence of intraoperative adverse events, is associated with an increased risk of developing anastomotic leakage.

Background: In order to improve the consistency of anaesthetic risk scoring, we have developed an automated method for the calculation of ASA (cASA) scores using decision logic programming. We investigated whether ASA scoring by anaesthetic caregivers could be matched or closely approximated by a cASA., Methods: We used a web-based preoperative assessment system to present a structured questionnaire comprising 22 questions. These were designed to score and identify conditions that are known, from the literature and expert opinion, to be risk factors. The answers from 14,349 cases were processed using decision logic to provide a variety of risk scores including a computed overall anaesthetic risk (cASA), which was then compared with the ASA score estimated by anaesthesia caregivers (eASA)., Results: We found a close agreement between the two measures in almost all cases. In 159 cases (1.1%), there was an underestimation of cASA, in comparison with the eASA, which appeared to be a result predominantly of incorrect or incomplete answers, or an overestimation of the ASA score by the human classifier (43%)., Conclusion: We showed that ASA scores estimated by a heterogeneous group of anaesthesia caregivers (anaesthetists, anaesthesia trainees, and physician assistants) could be mimicked by the cASA computed by our preoperative assessment system.

Objective: To study the incidence of hypoxaemia and bradycardia in children who undergo guillotine adenotonsillectomy in a sitting position, without intubation and under inhalation anaesthesia., Design: Retrospective study., Method: Analysis of age, weight, sex, oxygen saturation, heart rate and subsequent bleeding in all children up to the age of 11 years who underwent guillotine adenotonsillectomy in the period December 1999 to December 2007. Hypoxaemia was defined as oxygen saturation of less than 85% for longer than 60 s. Bradycardia was defined as a heart rate of less than 60/min for longer than 30 s., Results: We analysed data from 2963 patients. The mean age was 4.7 years and mean weight 18.8 kg. There was no significant relationship between age, weight and the onset of incidental desaturation or bradycardia. A total of 132 patients (4.5%) had hypoxaemia and 280 patients (9.4%) had bradycardia. Twenty-five patients had both hypoxaemia and bradycardia, of whom 3 (0.1%) had bradycardia immediately following hypoxaemia. In none of the recorded episodes of hypoxaemia and bradycardia did this lead to peri- or postoperative complications., Conclusion: Hypoxaemia and bradycardia occurred during guillotine adenotonsillectomy in non-intubated children in a sitting position under inhalation anaesthesia. The simultaneous onset of hypoxaemia and bradycardia is rare, however, and does not lead to perioperative complications. A further study is required using adenotonsillectomy with a large number of intubated and non-intubated children in order to compare the incidence of hypoxaemia and bradycardia and the occurrence of complications.

We studied the effect of large-dose intrathecal sufentanil (ITS) for major abdominal surgery on the hormonal stress response. Forty patients were randomly allocated to receive either IV sufentanil (IVS) or 150 microg of ITS as part of general anesthesia. In the IVS group, adrenocorticotropic hormone (ACTH) and cortisol concentrations were larger than baseline and the ITS group, 60 min after incision and at skin closure. Plasma concentrations of cortisol and ACTH were not different from baseline in the ITS group during surgery. Six hours after skin closure, cortisol concentrations were larger than baseline in both groups. Twenty-four and 48 h after skin closure, ACTH and cortisol values were similar between groups. Norepinephrine concentrations increased after surgery in both groups. Blood glucose levels increased in both groups during and after surgery. Pain scores and morphine consumption during the first 48 h after surgery were lower in the ITS group. The data show that large-dose ITS prevents the intraoperative hormonal stress response in comparison with balanced anesthesia. We speculate that this is due to the highly specific binding of sufentanil to spinal and supraspinal receptors. This technique improves postoperative analgesia when compared with balanced anesthesia.

Background: Duration of hospitalization after laparoscopic cholecystectomy (LC) is mainly determined by temporary side effects such as pain, nausea, and vomiting. In this study we compared remifentanil, a short acting opioid, and sufentanil, a longer acting opioid, on their ability to reduce these postoperative effects and facilitate LC in day case surgery., Method: Seventy patients scheduled for elective LC were randomized in two groups. Remifentanil was used in group 1 as part of the anesthetic protocol, sufentanil was used in group 2. After surgery, patients were asked to evaluate pain and nausea on a verbal rate scale (VRS). Frequency of vomiting and analgesic medication consumption was registered. Time between surgery and to the start of micturition, drinking, mobilization, dressing, and discharge was recorded. Patients registered their satisfaction on a VRS. Details of any other adverse events throughout the study were recorded., Results: Twenty-two patients (63%) of group 1 were treated as day cases vs. 27 (77%) in group 2 (P = NS). All patients who were not discharged as day cases left the hospital one day postoperatively. Immediately after surgery, patients in group 2 reported significantly less pain. There were no other significant differences between groups., Conclusion: The majority of patients scheduled for LC can be safely discharged on the day of surgery. Reported satisfaction one week postoperatively was high for all patients. We found no major relevant differences between the two anesthetic protocols.

The objective of this study was to determine a dosing regimen for remifentanil-sevoflurane anaesthesia that achieves an optimal balance between quality of anaesthesia and time to recovery. Patients undergoing elective laparoscopic cholecystectomy were randomly allocated to receive 0.4, 0.8 or 1.2 MAC (minimal alveolar concentration) of sevoflurane combined with remifentanil as required to maintain stable anaesthesia. For induction of anaesthesia, the remifentanil dose was 25 microg x kg(-1) x h(-1) and the mean propofol dose which was required to obtain loss of consciousness was 1.59 mg x kg(-1). During the maintenance phase, the mean remifentanil dose was 16.0, 14.1 and 13.0 microg x kg(-1) x h(-1) for the 0.4, 0.8 and 1.2 MAC groups, respectively. The mean sevoflurane maintenance dose was 0.91, 1.24 and 2.1% end-tidal for the 0.4, 0.8 and 1.2 MAC groups, respectively. The incidence of somatic responses was significantly higher in the 0.4 MAC sevoflurane group. Recovery times were significantly faster in the 0.4 compared to the 0.8 and 1.2 MAC groups and in the 0.8 compared to the 1.2 MAC group. The combination of 14 microg x kg(-1) x h(-1) remifentanil and 1.24% end-tidal sevoflurane achieved the optimal balance between the quality, and recovery from anaesthesia.

Study Objective: To compare the effectiveness of granisetron with placebo in the treatment of established postoperative nausea and vomiting (PONV)., Design: Randomized, placebo-controlled study., Setting: 34 hospitals in Europe, Scandinavia, and South Africa., Patients: 519 ASA physical status I, II, and III patients who developed PONV within 4 hours of the end of surgery performed with general anesthesia., Interventions: Patients received a single intravenous dose of granisetron 0.1 mg, 1 mg, or 3 mg, or placebo when symptoms of nausea or vomiting were experienced. Additional rescue medication could be given at the investigator's discretion if nausea and vomiting were not controlled., Measurements and Main Results: At all doses investigated, granisetron was significantly more effective (p < or = 0.001) than placebo in controlling vomiting: 38%, 46%, and 49% of patients receiving granisetron, 0.1 mg, 1.0 mg, and 3.0 mg, respectively, experienced no vomiting in the first 24 hours following drug administration, compared with 20% receiving placebo. There was a statistically significant linear relationship between vomiting control and granisetron dose (p < 0.001). Survival distributions of time to resolution of vomiting confirmed the statistically significant difference between patients receiving granisetron and those receiving placebo. Granisetron was well tolerated: the most common adverse experiences were pain, constipation, anemia, and headache, and the incidence of adverse experiences was not statistically significantly higher in any of the granisetron groups than in the placebo group., Conclusion: Granisetron was significantly more effective than placebo in all groups. Further studies in specific subgroups may be warranted.

Sixty ASA Grade II-III patients, without clinical symptoms of ventricular dysfunction and scheduled for elective bifemoral grafting for abdominal aneurysms, were allocated randomly to three equal groups to receive 150 micrograms sufentanil intravenously, epidurally or intrathecally. All patients received midazolam, vecuronium and nitrous oxide. Except for right ventricular stroke work index and pulmonary vascular resistance, all haemodynamic measurements decreased after sufentanil injection, but to the greatest extent after intravenous injection. Response to abdominal incision reversed the haemodynamic changes, although this was not accompanied by an increase in heart rate and coronary perfusion pressure after intrathecal injection. Four patients given intravenous, and four patients given epidural sufentanil required additional sufentanil after abdominal incision. Despite the changes in systemic vascular resistance and the concordant alterations in cardiac index after aortic cross-clamping and revascularization, intrathecal sufentanil provided more stability in heart rate than intravenous or epidural sufentanil. In conclusion, intrathecal sufentanil produced the most stable heart rate. Two patients in the intrathecal group developed spinal headaches post-operatively.

The haemodynamic changes associated with intrathecal morphine (IM) compared to intrathecal sufentanil (IS) as a supplement to general anaesthesia for elective bypass grafting in patients with aortoiliac occlusive disease were studied. Thirty-six, ASA Grade 2, patients randomly received morphine hydrochloride (0.1%) 50 micrograms kg-1 (n = 18) or undiluted sufentanil, 150 micrograms (n = 18) intrathecally at T12-L1, combined with light general anaesthesia. Haemodynamics were measured before and after endotracheal intubation, abdominal incision, aortic cross-clamping and the first revascularisation. The major differences were recorded after abdominal incision. Heart rate, systemic blood pressure and coronary perfusion pressure were significantly lower in the IS group. The probable cause was greater systemic absorption of sufentanil and its faster binding to the specific opiate receptors, resulting in a more efficacious supraspinal and spinal blockade during the first surgical period. However, both opioids provided adequate analgesia during the whole surgical procedure.

The present study was designed to evaluate the influence of epidural sufentanil (ES) and intrathecal sufentanil (IS) on the peri-operative haemodynamic responses during abdominal aortic surgery. Twenty-four ASA Grade II patients without clinical symptoms of coronary artery disease received, randomly, epidural (n = 12) or intrathecal (n = 12) sufentanil combined with light general anaesthesia for elective bifemoral grafting for aorto-iliac occlusive disease. The IS group contained significantly more hypertensive patients than the ES group. This resulted in a significantly higher systolic and mean blood pressure, which remained constant from the start to the end of the study. Following a single bolus injection of 150 micrograms of sufentanil epidurally or intrathecally, there was a significant decrease in heart rate (HR), systolic, mean and diastolic blood pressure, systemic vascular resistance (SVR) and coronary perfusion pressure in both groups. This suggests that IS and ES must be used with caution in patients with cardiovascular disease. The abdominal incision restored the haemodynamic changes produced by sufentanil administration, but these did not exceed pre-sufentanil values. There were no significant changes in filling pressure, cardiac index (CI) and left ventricular work after aortic cross-clamping in the two groups. Revascularization produced significant differences in HR, SVR and CI in both groups in comparison with the pre-declamping period. Notable was the maintenance of systemic blood pressure following revascularization due to preservation of sympathetic activity. It was concluded that both epidural and intrathecal sufentanil produce comparable and stable haemodynamics in this category of patients.

The present study was designed to compare the hemodynamic changes of epidural bupivacaine (EB) with epidural sufentanil (ES), supplemented by general anesthesia, in patients scheduled for abdominal aorto-iliac surgery. Twenty-eight ASA Grade 2 patients randomly received bupivacaine 0.5%, 1-1.5 mg kg-1 (n = 14) or sufentanil 150 micrograms (n = 14) epidurally at T12-L1, combined with light general anesthesia. Hemodynamics were measured before (T1) and after (T2) injection of EB or ES, after induction of general anesthesia (T3), and during the aortic dissection period (T4). EB or ES injection both produced a significant decrease in systolic, mean and diastolic blood pressure, left ventricular stroke work index (LVSWI) and coronary perfusion pressure (CPP). The induction of general anesthesia caused a significant fall in heart rate (HR) and cardiac index (CI) in the ES group. Abdominal dissection restored systemic pressure and cardiac index in the ES group. It was concluded that both ES and EB provided adequate analgesia and hemodynamics during tracheal intubation and abdominal dissection for aorto-iliac surgery.

We have studied the plasma concentrations (Cp) and pharmacokinetics of sufentanil injected i.v. (IVS), intradurally (IS) or extradurally (ES) under general anaesthesia in 31 patients undergoing major abdominal surgery. Sufentanil appeared in plasma very rapidly and Cpmax was also attained rapidly after both extradural and intrathecal injection. Apart from the first 2 min after injection, Cp after ES and IVS were comparable until the end of the study. Cp after ES was greater than after IS up to 0.25 h. Cp after IS was significantly greater than that after ES at 1 h and 2.5 h, and was also greater than that after IVS at 3 h. At tracheal extubation there was no difference in Cp between groups. Peak Cp values were significantly different between ES and IS, but the times taken to reach Cpmax were comparable. Plasma pharmacokinetics after ES and IS were similar. The plasma mean residence time and volume of distribution of sufentanil at steady state after ES and IS were significantly different in comparison with those after IVS.