Accuracy of the Nova StatStrip® glucometer in patients undergoing major abdominal surgery: an observational study.

PURPOSE: While the Nova StatStrip® Glucose Hospital Meter System (Nova Biomedical, Waltham, MA, USA) is approved for point-of-care testing (POCT) in critically ill patients, its use during major abdominal surgery has not been evaluated. The purpose of this study was to assess the accuracy of the Nova StatStrip glucometer in patients undergoing major hepatobiliary procedures using the Parkes error grid (ISO15197:2013) and criteria defined by the Clinical and Laboratory Standards Institute (CLSI) POCT12-A3 guideline. METHODS: This study was a post hoc exploratory study of patients participating in a prospective randomized controlled trial on the effects of hyperinsulinemic normoglycemia (HNC) on infectious outcomes after hepatobiliary surgery. Arterial blood samples were collected before surgery and one hour, two hours, and three hours after baseline. Blood glucose levels were analyzed by the Nova StatStrip glucometer and the GEM® PremierTM 5000 blood gas analyzer. Accuracy of the StatStrip glucometer was assessed using the Parkes error grid for type 1 diabetes mellitus (when 99% of samples were within zones A and B on the Parkes error grid and clinical accuracy was acceptable) and the CLSI POCT12-A3 criteria. RESULTS: Blood glucose levels were analyzed in 135 patients, 70 of whom received the HNC. In the Parkes error grid plotted, all samples at all time-points were within zones A and B. The Nova StatStrip glucometer also satisfied CLSI POCT12-A3 criteria at all time-points. CONCLUSION: The Nova StatStrip glucometer was accurate in patients undergoing major upper abdominal surgery, independent of the administration of high-dose insulin therapy. STUDY REGISTRATION: ClinicalTrials.gov (NCT01528189); registered 7 February 2012.

RéSUMé: OBJECTIF: Bien que le système hospitalier de lecture de la glycémie StatStrip® de Nova (Nova Biomedical, Waltham, MA, É.-U.) soit approuvé pour une utilisation au chevet (ou POCT, pour 'Point of Care Testing') chez la patientèle en état critique, son utilisation n'a pas été évaluée en chirurgie abdominale majeure. L'objectif de cette étude était d'évaluer la précision du glucomètre StatStrip de Nova chez la patientèle bénéficiant d'interventions hépatobiliaires majeures à l'aide de la grille d'erreur de Parkes (ISO15197:2013) et des critères définis par la directive POCT12-A3 du Clinical and Laboratory Standards Institute (CLSI). MéTHODE: Il s'agissait d'une étude exploratoire post-hoc auprès de patient·es participant à une étude randomisée contrôlée prospective sur les effets de la normoglycémie hyperinsulinémique (HNC) sur les issues infectieuses après une chirurgie hépatobiliaire. Des échantillons de sang artériel ont été prélevés avant la chirurgie et une heure, deux heures et trois heures après l'échantillon initial. Les taux de glycémie ont été analysés avec le glucomètre StatStrip de Nova et l'analyseur de gaz sanguin GEM® PremierTM 5000. La précision du glucomètre StatStrip a été évaluée à l'aide de la grille d'erreur de Parkes pour le diabète sucré de type 1 (lorsque 99 % des échantillons se trouvaient dans les zones A et B de la grille d'erreur de Parkes et que la précision clinique était acceptable) et des critères POCT12-A3 du CLSI. RéSULTATS: La glycémie a été analysée chez 135 personnes, dont 70 ont reçu une normoglycémie hyperinsulinémique. Dans la grille d'erreur de Parkes tracée, tous les échantillons à tous les points temporels se trouvaient dans les zones A et B. Le glucomètre StatStrip de Nova a également satisfait aux critères POCT12-A3 du CLSI à tous les points temporels. CONCLUSION: Le glucomètre StatStrip de Nova était précis chez la patientèle bénéficiant d'une chirurgie abdominale supérieure majeure, indépendamment de l'administration d'insulinothérapie à forte dose. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT01528189); enregistrée le 7 février 2012.

Albumin and fibrinogen kinetics in sepsis: a prospective observational study.

BACKGROUND: The measurement of circulating substrate concentrations does not provide information about substrate kinetics. It, therefore, remains unclear if a decrease in plasma concentration of albumin, as seen during critical illness, is a consequence of suppressed production in the liver or increased peripheral clearance. In this study, using stable isotope tracer infusions, we measured albumin and fibrinogen kinetics in septic patients and in a control group of non-septic subjects. METHODS: With the approval from the institutional Research Ethics Board and after obtaining written informed consent from patients or their substitute decision maker, mechanically ventilated patients with sepsis and patients scheduled for elective coronary artery bypass grafting were enrolled. Patients in the non-sepsis group were studied on the day before surgery. The stable isotope L-[ring-2H5]phenylalanine was used to measure absolute synthesis rates (ASR) of albumin and fibrinogen. A priming dose of L-[ring-2H5]phenylalanine (4 µmol/kg) was given followed by a six-hour infusion at a rate of 0.15 µmol/kg/min. At baseline and hourly thereafter, blood was drawn to measure isotope enrichments by gas chromatography/mass spectrometry. Very low density lipoprotein apolipoprotein-B 100 isotopic enrichment was used to represent the isotopic enrichment of the phenylalanine precursor pool from which the liver synthesizes proteins. Plasma albumin and fibrinogen concentrations were also measured. RESULTS: Mean plasma albumin in septic patients was decreased when compared to non-septic patients, while synthesis rates were comparable. Mean plasma fibrinogen and ASR in septic patients was increased when compared to non-septic patients. In non-septic patients, no statistically significant correlation between plasma albumin and ASR was observed but plasma fibrinogen significantly correlated with ASR. In septic patients, plasma albumin and fibrinogen significantly correlated with ASR. CONCLUSIONS: While septic patients showed lower plasma albumin levels than non-septic patients, albumin synthesis was similar in the two groups suggesting that hypoalbuminemia during sepsis was not caused by suppressed hepatic production but a result of enhanced clearance from the circulation. Hyperfibrinogenemia in septic patients was a consequence of increased fibrinogen production. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02865408 (registered on August 12, 2016) and ClinicalTrials.gov: NCT02549443 (registered on September 15, 2015).

Intranasal administration of 40 and 80 units of insulin does not cause hypoglycemia during cardiac surgery: a randomized controlled trial.

PURPOSE: Intranasal insulin administration may improve cognitive function in patients with dementia and may prevent cognitive problems after surgery. Although the metabolic effects of intranasal insulin in non-surgical patients have been studied, its influence on glucose concentration during surgery is unknown. METHODS: We conducted a randomized, double-blind, placebo-contolled trial in patients scheduled for elective cardiac surgery. Patients with type 2 diabetes mellitus (T2DM) and non-T2DM patients were randomly allocated to one of three groups (normal saline, 40 international units [IU] of intranasal insulin, and 80 IU intranasal insulin). Insulin was given after the induction of general anesthesia. Glucose and plasma insulin concentrations were measured in ten-minute intervals during the first hour and every 30 min thereafter. The primary outcome was the change in glucose concentration 30 min after intranasal insulin administration. RESULTS: A total of 115 patients were studied, 43 of whom had T2DM. In non-T2DM patients, 40 IU intranasal insulin did not affect glucose concentration, while 80 IU intranasal insulin led to a statistically significant but not clinically important decrease in blood glucose levels (mean difference, 0.4 mMol·L-1; 95% confidence interval, 0.1 to 0.7). In T2DM patients, neither 40 IU nor 80 IU of insulin affected glucose concentration. No hypoglycemia (< 4.0 mMol·L-1) was observed after intranasal insulin administration in any patients. In non-T2DM patients, changes in plasma insulin were similar in the three groups. In T2DM patients, there was an increase in plasma insulin concentrations ten minutes after administration of 80 IU of intranasal insulin compared with saline. CONCLUSIONS: In patients with and without T2DM undergoing elective cardiac surgery, intranasal insulin administration at doses as high as 80 IU did not cause clinically important hypoglycemia. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT02729064); registered 5 April 2016.

RéSUMé: OBJECTIF: L'administration intranasale d'insuline pourrait améliorer la fonction cognitive des patients souffrant de démence et pourrait prévenir les problèmes cognitifs après une chirurgie. Bien que les effets métaboliques de l'insuline intranasale chez les patients non chirurgicaux aient été étudiés, son influence sur la glycémie pendant une chirurgie est inconnue. MéTHODE: Nous avons réalisé une étude randomisée, à double insu, contrôlée par placebo auprès de patients devant subir une chirurgie cardiaque non urgente. Des patients atteints de diabète de type 2 et des patients non diabétiques ont été randomisés dans l'un de trois groupes (solution physiologique salée, 40 unités internationales [UI] d'insuline intranasale et 80 UI d'insuline intranasale). La solution intranasale a été administrée après l'induction de l'anesthésie générale. Les concentrations de glucose et d'insuline plasmatique ont été mesurées à des intervalles de dix minutes pendant la première heure et toutes les 30 minutes par la suite. Le critère d'évaluation principal était le changement de glycémie 30 min après l'administration intranasale d'insuline. RéSULTATS: Un total de 115 patients ont été étudiés, dont 43 souffraient de diabète de type 2. Chez les patients non diabétiques, 40 UI d'insuline intranasale n'ont pas affecté la glycémie, alors que 80 UI d'insuline intranasale ont entraîné une réduction statistiquement significative mais non cliniquement importante de la glycémie (différence moyenne, 0,4 mMol·L−1; intervalle de confiance de 95 %, 0,1 à 0,7). Chez les patients diabétiques, ni 40 UI ni 80 UI d'insuline n'ont affecté la glycémie. Aucune hypoglycémie (< 4,0 mMol·L−1) n'a été observée après administration intranasale d'insuline chez les patients diabétiques ou non diabétiques. Chez les patients non diabétiques, les changements de l'insuline plasmatique étaient semblables dans les trois groupes. Chez les patients diabétiques, une augmentation des concentrations d'insuline plasmatique a été observée dix minutes après l'administration de 80 UI d'insuline intranasale comparée à la solution saline. CONCLUSION: Chez les patients diabétiques et non diabétiques subissant une chirurgie cardiaque non urgente, l'administration intranasale d'insuline à des doses allant jusqu'à 80 UI n'a pas causé d'hypoglycémie cliniquement importante. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT02729064); enregistrée le 5 avril 2016.

Risk of stroke and other adverse outcomes in patients with perioperative atrial fibrillation 1 year after non-cardiac surgery.

AIMS: To determine the 1-year risk of stroke and other adverse outcomes in patients with a new diagnosis of perioperative atrial fibrillation (POAF) after non-cardiac surgery. METHODS AND RESULTS: The PeriOperative ISchemic Evaluation (POISE)-1 trial evaluated the effects of metoprolol vs. placebo in 8351 patients, and POISE-2 compared the effect of aspirin vs. placebo, and clonidine vs. placebo in 10 010 patients. These trials included patients with, or at risk of, cardiovascular disease who were undergoing non-cardiac surgery. For the purpose of this study, we combined the POISE datasets, excluding 244 patients who were in atrial fibrillation (AF) at the time of randomization. Perioperative atrial fibrillation was defined as new AF that occurred within 30 days after surgery. Our primary outcome was the incidence of stroke at 1 year of follow-up; secondary outcomes were mortality and myocardial infarction (MI). We compared outcomes among patients with and without POAF using multivariable adjusted Cox proportional hazards models. Among 18 117 patients (mean age 69 years, 57.4% male), 404 had POAF (2.2%). The stroke incidence 1 year after surgery was 5.58 vs. 1.54 per 100 patient-years in patients with and without POAF, adjusted hazard ratio (aHR) 3.43, 95% confidence interval (CI) 2.00-5.90; P < 0.001. Patients with POAF also had an increased risk of death (incidence 31.37 vs. 9.34; aHR 2.51, 95% CI 2.01-3.14; P < 0.001) and MI (incidence 26.20 vs. 8.23; aHR 5.10, 95% CI 3.91-6.64; P < 0.001). CONCLUSION: Patients with POAF have a significantly increased risk of stroke, MI, and death at 1 year. Intervention studies are needed to evaluate risk reduction strategies in this high-risk population.

Intravenous lidocaine to prevent postoperative airway complications in adults: a systematic review and meta-analysis.

BACKGROUND: In surgical patients undergoing general anaesthesia, coughing at the time of extubation is common and can result in potentially dangerous complications. We performed a systematic review and meta-analysis to assess the efficacy and safety of i.v. lidocaine administration during the perioperative period to prevent cough and other airway complications. METHODS: We searched Medical Literature Analysis and Retrieval System, Excerpta Medica database, and Cochrane Central Register of Controlled Trials for RCTs comparing the perioperative use of i.v. lidocaine with a control group in adult patients undergoing surgery under general anaesthesia. The RCTs were assessed using risk-of-bias assessment, and the quality of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULTS: In 16 trials (n=1516), the administration of i.v. lidocaine compared with placebo or no treatment led to large reductions in post-extubation cough (risk ratio [RR]: 0.64; 95% confidence interval [CI]: 0.48-0.86) and in postoperative sore throat at 1 h (RR: 0.46; 95% CI: 0.32-0.67). There was no difference in incidence of laryngospasm (risk difference [RD]: 0.02; 95% CI: -0.07 to 0.03) or incidence of adverse events related to the use of lidocaine. CONCLUSIONS: The use of i.v. lidocaine perioperatively decreased airway complications, including coughing and sore throat. There was no associated increased risk of harm.

Accuracy of blood glucose measurements using the NOVA StatStrip® glucometer during cardiac surgery: a prospective observational study.

PURPOSE: The Nova StatStrip® Glucose Hospital Meter System (Nova Biomedical, Waltham, MA, USA) is United States Food and Drug Administration approved for point-of-care use in critically ill patients, but its use during cardiac surgery has not been evaluated. In this study, we compare glucose values obtained during cardiac surgery by StatStrip® with values obtained by a blood gas analyzer. METHODS: Blood glucose concentrations were analyzed in 121 patients by the StatStrip point- of-care test (POCT) glucose monitor and the GEM® Premier™ 3000 blood gas analyzer (Instrumentation Laboratory Company, Bedford MA, USA). Arterial blood samples were taken at baseline (before surgery), before cardiopulmonary bypass (CPB), during early and late CPB, and 30 min after CPB. Accuracy of the StatStrip glucometer was analyzed using the Clinical and Laboratory Standards Institute (CLSI) POCT12-A3 criteria (criterion 1; 95% of samples should be ± 0.66 mMol·L-1 of reference glucose values < 5.5 mMol·L-1 and ± 12.5% for reference glucose values > 5.5 mMol·L-1, criterion 2; 98% of samples should be ± 0.83 mMol·L-1 of reference glucose values < 4.1 mMol·L-1 or 20% of the reference glucose for values > 4.1 mMol·L-1). RESULTS: The accuracy of StatStrip glucose measurements at baseline (99%, 100%) and before CPB (95%, 98%), but not during (early: 84%, 97%; late: 83%, 96%) and after (92%, 100%) CPB, satisfied the CLSI POCT12-A3 criteria. CONCLUSION: Arterial blood glucose measurement by StatStrip was accurate before CPB, but lacked accuracy during and after CPB. Glucose values should be interpreted with caution when intensive glucose control protocols are being used during cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02729064); registered 5 April, 2016.

RéSUMé: OBJECTIF: Le glucomètre hospitalier StatStrip® de Nova (Nova Biomedical, Waltham, MA, É.-U.) est approuvé par la FDA (Food and Drug Administration) américaine pour une utilisation au chevet chez les patients en état critique, mais son utilisation n'a pas été évaluée en chirurgie cardiaque. Dans cette étude, nous avons comparé les valeurs glycémiques obtenues par le lecteur StatStrip® et les valeurs obtenues par un analyseur des gaz du sang pendant une chirurgie cardiaque. MéTHODE: Les concentrations glycémiques de 121 patients ont été analysées en utilisant le moniteur glycémique StatStrip et l'analyseur de gaz sanguins GEM® Premier™ 3000 (Instrumentation Laboratory Company, Bedford, MA, É.-U.). Des échantillons de sang artériel ont été prélevés avant la chirurgie, avant la circulation extracorporelle (CEC), au début et à la fin de la CEC et 30 min après la CEC. La précision du glucomètre StatStrip a été analysée à l'aide des critères de l'Institut des normes cliniques et de laboratoire (Clinical and Laboratory Standards Institute (CLSI)) POCT12-A3 (1er critère; 95 % des échantillons doivent être à l'intérieur de ± 0,66 mMol·L−1 des valeurs glycémiques de référence < 5,5 mMol·L−1 et ± 12,5 % pour les valeurs glycémiques de référence > 5,5 mMol·L−1, 2ème critère; 98 % des échantillons doivent être à l'intérieur de ± 0,83 mMol·L−1 des valeurs glycémiques de référence < 4,1 mMol·L−1 ou 20 % du taux glycémique de référence pour les valeurs > 4,1 mMol·L−1). RéSULTATS: La précision des mesures glycémiques prises par le StatStrip avant l'opération (99 %, 100 %) et avant la CEC (95 %, 98 %), mais non durant (début : 84 %, 97 %; fin : 83 %, 96 %) et après (92 %,100 %) la CEC, respectait les critères POCT12-A3 du CLSI. <0} CONCLUSION: La mesure de la glycémie artérielle réalisée avec le StatStrip était précise avant la CEC mais a manqué de précision pendant et après la CEC. Les valeurs glycémiques devraient donc être interprétées avec prudence lorsque des protocoles intensifs de contrôle glycémique sont utilisés pendant une chirurgie cardiaque. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02729064); enregistrée le 5 avril 2016.

Awake videolaryngoscopy versus fiberoptic bronchoscopy.

PURPOSE OF REVIEW: The difficult airway remains an ongoing concern in daily anesthesia practice, with awake intubation being an important component of its management. Classically, fiberoptic bronchoscope-assisted tracheal intubation was the method of choice in the awake patient. The development of new generation videolaryngoscopes has revolutionized the approach to tracheal intubation in the anesthetized patient. The question whether videolaryngoscopes have a place in the intubation of the difficult airway in the awake patient is currently being addressed. RECENT FINDINGS: Randomized controlled trials and their meta-analysis have shown that videolaryngoscopes provide similar success rates and faster intubation times when compared with fiberoptic bronchoscope intubation in awake patients with difficult airways. SUMMARY: Videolaryngoscopy is a valid technique that should be considered for difficult airway management in the awake patient.

Hyperinsulinemic Normoglycemia during Cardiac Surgery Reduces a Composite of 30-day Mortality and Serious In-hospital Complications: A Randomized Clinical Trial.

BACKGROUND: Hyperinsulinemic normoglycemia augments myocardial glucose uptake and utilization. We tested the hypothesis that hyperinsulinemic normoglycemia reduces 30-day mortality and morbidity after cardiac surgery. METHODS: This dual-center, parallel-group, superiority trial randomized cardiac surgical patients between August 2007 and March 2015 at the Cleveland Clinic, Cleveland, Ohio, and Royal Victoria Hospital, Montreal, Canada, to intraoperative glycemic management with (1) hyperinsulinemic normoglycemia, a fixed high-dose insulin and concomitant variable glucose infusion titrated to glucose concentrations of 80 to 110 mg · dl; or (2) standard glycemic management, low-dose insulin infusion targeting glucose greater than 150 mg · dl. The primary outcome was a composite of 30-day mortality, mechanical circulatory support, infection, renal or neurologic morbidity. Interim analyses were planned at each 12.5% enrollment of a maximum 2,790 patients. RESULTS: At the third interim analysis (n = 1,439; hyperinsulinemic normoglycemia, 709, standard glycemic management, 730; 52% of planned maximum), the efficacy boundary was crossed and study stopped per protocol. Time-weighted average glucose concentration (means ± SDs) with hyperinsulinemic normoglycemia was 108 ± 20 versus 150 ± 33 mg · dl with standard glycemic management, P < 0.001. At least one component of the composite outcome occurred in 49 (6.9%) patients receiving hyperinsulinemic normoglycemia versus 82 (11.2%) receiving standard glucose management (P < efficacy boundary 0.0085); estimated relative risk (95% interim-adjusted CI) 0.62 (0.39 to 0.97), P = 0.0043. There was a treatment-by-site interaction (P = 0.063); relative risk for the composite outcome was 0.49 (0.26 to 0.91, P = 0.0007, n = 921) at Royal Victoria Hospital, but 0.96 (0.41 to 2.24, P = 0.89, n = 518) at the Cleveland Clinic. Severe hypoglycemia (less than 40 mg · dl) occurred in 6 (0.9%) patients. CONCLUSIONS: Intraoperative hyperinsulinemic normoglycemia reduced mortality and morbidity after cardiac surgery. Providing exogenous glucose while targeting normoglycemia may be preferable to simply normalizing glucose concentrations.

Perioperative fluid management in kidney transplantation: a black box.

The incidence of delayed graft function in patients undergoing kidney transplantation remains significant. Optimal fluid therapy has been shown to decrease delayed graft function after renal transplantation. Traditionally, the perioperative volume infusion regimen in this patient population has been guided by central venous pressure as an estimation of the patient's volume status and mean arterial pressure, but this is based on sparse evidence from mostly retrospective observational studies. Excessive volume infusion to the point of no further fluid responsiveness can damage the endothelial glycocalyx and is no longer considered to be the best approach. However, achievement of adequate flow to maintain sufficient tissue perfusion without maximization of cardiac filling remains a challenge. Novel minimally invasive technologies seem to reliably assess volume responsiveness, heart function and perfusion adequacy. Prospective comparative clinical studies are required to better understand the use of dynamic analyses of flow parameters for adequate fluid management in kidney transplant recipients. We review perioperative fluid assessment techniques and discuss conventional and novel monitoring strategies in the kidney transplant recipient.

Age Does Not Affect Metoprolol's Effect on Perioperative Outcomes (From the POISE Database).

BACKGROUND: Perioperative ß-blockade reduces the incidence of myocardial infarction but increases that of death, stroke, and hypotension. The elderly may experience few benefits but more harms associated with ß-blockade due to a normal effect of aging, that of a reduced resting heart rate. The tested hypothesis was that the effect of perioperative ß-blockade is more significant with increasing age. METHODS: To determine whether the effect of perioperative ß-blockade on the primary composite event, clinically significant hypotension, myocardial infarction, stroke, and death varies with age, we interrogated data from the perioperative ischemia evaluation (POISE) study. The POISE study randomly assigned 8351 patients, aged ≥45 years, in 23 countries, undergoing major noncardiac surgery to either 200 mg metoprolol CR daily or placebo for 30 days. Odds ratios or hazard ratios for time to events, when available, for each of the adverse effects were measured according to decile of age, and interaction term between age and treatment was calculated. No adjustment was made for multiple outcomes. RESULTS: Age was associated with higher incidences of the major outcomes of clinically significant hypotension, myocardial infarction, and death. Age was associated with a minimal reduction in resting heart rate from 84.2 (standard error, 0.63; ages 45-54 years) to 80.9 (standard error, 0.70; ages >85 years; P < .0001). We found no evidence of any interaction between age and study group regarding any of the major outcomes, although the limited sample size does not exclude any but large interactions. CONCLUSIONS: The effect of perioperative ß-blockade on the major outcomes studied did not vary with age. Resting heart rate decreases slightly with age. Our data do not support a recommendation for the use of perioperative ß-blockade in any age subgroup to achieve benefits but avoid harms. Therefore, current recommendations against the use of ß-blockers in high-risk patients undergoing noncardiac surgery apply across all age groups.

Body mass index predicts insulin sensitivity during cardiac surgery: a prospective observational study.

PURPOSE: Taking into account the previously described link between body weight and diabetes mellitus (DM) in non-surgical patients, and the understanding that the degree of intraoperative insulin resistance is a predictor of adverse clinical outcomes, we investigated the relationship between body mass index (BMI) and insulin sensitivity during cardiac surgery. METHODS: We prospectively enrolled 400 patients scheduled for elective cardiac surgery and divided them into groups based on the presence or absence of type-2 DM. They were further categorized into four subgroups based on their BMI: group 1- normal weight, BMI 18.5-24.9 kg·m-2; group 2 - overweight, BMI 25-29.9 kg·m-2; group 3 - obese, BMI 30-34.9 kg·m-2; group 4 - morbidly obese, BMI ≥ 35 kg·m-2. Insulin sensitivity was assessed using the hyperinsulinemic-normoglycemic clamp technique during surgery. We also analyzed the association of BMI, quality of postoperative glycemic control, and postoperative outcomes. RESULTS: A linear negative relationship between BMI and insulin sensitivity (r = 0.42, P < 0.001) was observed, independent of the patients' diabetic state. There was also a positive correlation between BMI and postoperative glycemia (r = 0.30, P < 0.001) though the relationship between BMI and major and infectious complication was not significant (P = 0.56, P = 0.10, respectively). CONCLUSIONS: Patient BMI may be used as a simple predictor of insulin sensitivity during cardiac surgery and as a predictor of the quality of postoperative glycemic control. A larger cohort will be necessary to evaluate the association of BMI, perioperative insulin resistance, and clinical outcomes.

Glycemia and the cardioprotective effects of insulin pre-conditioning in the isolated rat heart.

BACKGROUND: While acute hyperglycemia has been shown to mitigate the beneficial effects of ischemic preconditioning, its effect on insulin-induced preconditioning remains unclear. METHODS: The study was designed to test the hypothesis that acute hyperglycemia diminishes the cardioprotective effects following a 20-min pre-ischemic pre-conditioning with insulin in the isolated rat heart using the Langendorff system. Forty hearts were assigned to receive modified Krebs-Henseleit (KH) buffer containing 0.5 U/L insulin and 100 mg/dL glucose (InsG100, n = 10), KH buffer with 100 mg/dL glucose (G100, n = 10), KH buffer supplemented with 0.5 U/L insulin and 600 mg/dL glucose (InsG600, n = 10), or with 600 mg/dL glucose (G600, n = 10). To match the osmotic pressure of the InsG600 group, 27.5 mmol/L of mannitol was added to KH solution in the InsG100 and G100 group. The four groups were perfused with each solution for 20 min prior to 15 min of no-flow ischemia, and during 20 min of reperfusion. Only during the ischemic period the heart was paced at 222 beats/min. Measurements of heart rate, coronary flow and maximum of LV derivative of pressure development (dP/dt max) were recorded. Myocardial phospho-protein kinase B (p-Akt) and tumor necrosis factor-α (TNF-α) levels were assayed by enzyme-linked immunosorbent assay and sandwich ELISA, respectively following reperfusion. RESULTS: After reperfusion, LV dP/dt max and heart rate in the InsG100 group was significantly higher than that in the other three groups. The myocardial p-Akt level in the InsG100 group was significantly elevated when compared to the InsG600 group at the end of reperfusion. The p-Akt levels in the InsG600 and InsG100 group were significantly higher than in the corresponding non-insulin groups. CONCLUSIONS: Acute hyperglycemia diminishes the cardioprotective effects of insulin preconditioning in the isolated rat heart, possibly mediated through the suppression of myocardial Akt phosphorylation.

Hyperinsulinemic-normoglycemic clamp administered together with amino acids induces anabolism after cardiac surgery.

Cardiac surgery triggers an inflammatory stress response, leading to protein catabolism, a process that even high-dose insulin therapy alone cannot reverse. To determine whether hyperinsulinemic-normoglycemic clamp and perioperative amino acid (AA) supplementation improves whole body protein balance, 20 patients scheduled for elective coronary artery bypass grafting surgery were randomly assigned to have intra- and postoperative hyperinsulinemic-normoglycemic clamp, with or without intravenous AA supplementation. Primed continuous infusions of [6,6-2H2]glucose and l-[1-13C]leucine were used to quantify whole body protein and glucose metabolism before and after surgery. Adipose tissue and serum cytokines were also analyzed to measure their responsiveness to the anabolic effect of AA administration. During hyperinsulinemic-normoglycemic clamp, AA supplementation successfully stimulated whole body protein synthesis, resulting in a positive whole body protein balance after surgery (insulin: -13.6 ± 4.5 vs. insulin + AA: 2.1 ± 5.4 µmol·kg-1·h-1, P < 0.001). Endogenous glucose production was equally suppressed in both groups (insulin: 0.0 ± 3.8 vs. insulin + AA 1.6 ± 1.6 µmol·kg-1·min-1, P = 0.230). AA supplementation led to significant changes in serum and tissue IL-6 (insulin: 246.6 ± 111.2 vs. insulin + AA: 124.5 ± 79.3 pg/ml, P = 0.011). In conclusion, hyperinsulinemic-normoglycemic clamp technique, together with AA supplementation, can induce an anabolic state after open-heart surgery, as quantified by a positive whole body protein balance.

The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial.

BACKGROUND: Nitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk. We aimed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk. METHODS: We did an international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery. Patients were randomly assigned via automated telephone service, stratified by site, to receive a general anaesthetic with or without nitrous oxide. Attending anaesthetists were aware of patients' group assignments, but patients and assessors were not. The primary outcome measure was a composite of death and cardiovascular complications (non-fatal myocardial infarction, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. Our modified intention-to-treat population included all patients randomly assigned to groups and undergoing induction of general anaesthesia for surgery. This trial is registered at ClinicalTrials.gov, number NCT00430989. FINDINGS: Of 10,102 eligible patients, we enrolled 7112 patients between May 30, 2008, and Sept 28, 2013. 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide. 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome. The primary outcome occurred in 283 (8%) patients receiving nitrous oxide and in 296 (8%) patients not receiving nitrous oxide (relative risk 0·96, 95% CI 0·83­1·12; p=0·64). Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61), and severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001). INTERPRETATION: Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery. Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection, the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis, and a desired effect of reduced volatile agent use was shown. FUNDING: Australian National Health and Medical Research Council; Australian and New Zealand College of Anaesthetists; Heart and Stroke Foundation of Quebec, Heart and Stroke Foundation of Ontario, Canada; General Research Fund of the Research Grant Council, Hong Kong Special Administrative Region, China.

Perioperative catabolism.

PURPOSE: This article reviews the pathophysiology, clinical relevance, and therapy of the catabolic response to surgical stress. PRINCIPLE FINDINGS: The key clinical features of perioperative catabolism are hyperglycemia and loss of body protein, both metabolic consequences of impaired insulin function. Muscle weakness and (even moderate) increases in perioperative blood glucose are associated with morbidity after major surgery. Although the optimal glucose concentration for improving clinical outcomes is unknown, most medical associations recommend treatment of random blood glucose > 10 mmol·L(-1). Neuraxial anesthesia blunts the neuroendocrine stress response and enhances the anabolic effects of nutrition. There is evidence to suggest that the avoidance of preoperative fasting prevents insulin resistance and accelerates recovery after major abdominal surgery. CONCLUSIONS: Current anticatabolic therapeutic strategies include glycemic control and perioperative nutrition in combination with optimal pain control and the avoidance of preoperative starvation. All these elements are part of Enhanced Recovery After Surgery (ERAS) programs.