Safety of intranasal insulin administration in patients undergoing cardiovascular surgery: An open-label, nonrandomized, dose-escalation study.

Objective: This study aimed to determine the maximum safe dose of intranasal insulin administration during cardiac surgery. Methods: This open-label, Phase 1, single-center, dose-escalation clinical trial recruited patients scheduled to undergo elective cardiac surgery or major vascular surgery requiring cardiopulmonary bypass between February and September 2021. They were grouped into 5 dose-escalation cohorts and administered 0, 40, 80, 160, and 240 IU insulin (n = 6 in each group) via a metered nasal dispenser after the induction of general anesthesia. Blood samples were collected at 10-minute intervals for the first 60 minutes and at 30-minute intervals thereafter. Hypoglycemia was defined as a blood glucose level <70 mg/dL. Patient recruitment was terminated after hypoglycemia was observed in 2 patients in any of the groups. Results: In total, 27 of 29 enrolled patients were administered intranasal insulin or saline. Hypoglycemia was not observed after the administration of intranasal insulin in the 0, 40, 80, or 160 IU groups; however, it was observed in 2 of 3 patients in the 240 IU group. The serum insulin concentration was elevated in the 160-IU group, but the C-peptide concentration was not elevated in any of the groups. Conclusions: The administration of up to 160 IU intranasal insulin did not induce clinically significant hypoglycemia. However, 160 IU intranasal insulin should be administered cautiously because insulin can enter the systemic circulation in a dose-dependent manner.

Effect of intranasal insulin administration on postoperative delirium prevention in elderly cardiac surgery patients: study protocol for a multicenter, double-blind, randomized, controlled trial.

BACKGROUND: Postoperative delirium (POD) is a complication after surgery which leads to worse outcomes. The frequency of this syndrome is increasing as more elderly patients undergo major surgery. The frequency is around 10-25% but reaches as high as 50% for cardiac surgery. Although intranasal insulin (INI) administration of up to 160 units in patients with cognitive dysfunction and delirium has been shown to improve memory function and brain metabolism without complications such as hypoglycemia, it remains unknown whether INI prevents POD after cardiac surgery METHODS: A multicenter, double-blind, randomized, controlled trial will be conducted at University of Tsukuba Hospital and Tsukuba Medical Center Hospital, Japan, from July 1, 2023, to December 31, 2025. A total of 110 elderly patients (65 years old or older) undergoing cardiac surgery requiring cardiopulmonary bypass will be enrolled and randomly allocated to intranasal insulin or intranasal saline groups. The primary outcome is the incidence of POD within 7 days after surgery. Secondary outcomes include days and times of delirium, screening tests of cognitive function, pain scores, duration of postoperative tracheal intubation, and length of ICU stay. DISCUSSION: The present objective is to assess whether 80 IU INI administration during surgery prevents POD after cardiac surgery. The results may provide strategic choices to prevent POD in patients with cardiac surgery requiring cardiopulmonary bypass. TRIAL REGISTRATION: The trial was registered with the Japan Registry for Clinical Trials with identifier jRCTs031230047  on April 21, 2023.

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.

Role of the protein kinase A signaling pathway and identification of mediators in the cardioprotective effects of enteral lactoferrin for ischemia-reperfusion injury in an isolated rat heart model.

OBJECTIVE: Lactoferrin is an iron-binding glycoprotein. Enteral lactoferrin attenuates myocardial ischemia-reperfusion (IR) injury, but the underlying mechanism remains unknown. The aim of this study was to investigate protein kinase A (PKA) signaling pathway activation and levels of serum glucagonlike peptide-1 (GLP-1), secreted by intestinal endocrine L cells, and adiponectin, secreted by adipose tissue, after enteral lactoferrin administration. METHODS: Hearts (N = 32) were excised from Wistar rats and perfused using a Langendorff system. To assess the role of the PKA pathway in the cardioprotective effects of lactoferrin, an inhibitor of PKA (H89) was applied before no-flow ischemia. Rats were randomly divided into four groups: control, lactoferrin (LF), control+H89, and LF+H89. The control and control+H89 groups were administered normal saline by gavage, and the LF and L +H89 groups were administered bovine lactoferrin (1000 mg/kg) by gavage 15 min before intraperitoneal pentobarbital injection. Muscle sampling was performed at the end of reperfusion. When rats were sacrificed, blood was sampled to measure hormone levels. The primary outcome was maximum left ventricular pressure derivative (LV dP/dt max) 15 min after reperfusion. RESULTS: LV dP/dt max at 10 and 15 min after reperfusion was significantly higher in the LF group than in the control group (P < 0.05), and the effect was diminished by H89. The PKA pathway was significantly activated in the LF group. Enteral lactoferrin increased serum GLP-1 but not serum adiponectin levels. CONCLUSIONS: Enteral lactoferrin induces cardioprotective effects against myocardial IR injury via the PKA signaling pathway and increases serum GLP-1 levels.

Risk factors for postoperative complications in patients with Parkinson disease: A single center retrospective cohort study.

Surgical treatment for patients with Parkinson disease (PD) under general anesthesia has become frequent. PD is a significant predictor of postoperative complications. However, the factors that predict complications in patients with PD remain unknown. We retrospectively recruited patients with PD who underwent surgery between April 2015 and March 2019. The prevalence of postoperative complications was analyzed. We compared the patient characteristics, medical data, and surgical data between patients with and without postoperative complications. We also estimated the odds ratios (OR) for postoperative complications in patients with PD who underwent surgery. Sixty-five patients were enrolled. Eighteen patients presented with 22 complications, including urinary tract infections (UTI) (n = 3; 5%), pneumonia (n = 1; 2%), surgical site infections (SSI) (n = 3; 5%), postoperative delirium (POD) (n = 7; 10%), and others (n = 8; 12%). Four patients presented with 2 complications each. The operation time, the red blood cell transfusion and the rate of rotigotine usage were higher in patients with complications than those without (314 ± 197 min vs 173 ± 145 min, P = .006; 0 [0-560] mL vs 0 [0-0] mL, P = .02; 39% vs 6%, P = .003, respectively) (mean ± standard deviation or median [interquartile range]). Preoperative rotigotine usage (OR: 9.33; 95% confidential interval [CI]: 2.07-42.07; P = .004) was an independent risk factors for postoperative complications. The findings indicate that clinicians should closely monitor postoperative complications when patients with PD who have received transdermal dopamine agonists undergone longer time surgery.

Cardioprotective effects of enteral vs. parenteral lactoferrin administration on myocardial ischemia-reperfusion injury in a rat model of stunned myocardium.

BACKGROUND: Lactoferrin, an iron-binding glycoprotein, is known to have protective effects against intestinal and cerebral ischemia-reperfusion (IR) injuries; however, its cardioprotective effects against the stunned myocardium are unknown. This study aimed to test the hypothesis that lactoferrin has cardioprotective effects against stunned myocardium. METHODS: Using isolated rat hearts (Langendorff system), we determined the effects of lactoferrin administered enterally and by direct cardiac perfusion. Rat hearts were perfused using the Langendorff system, and two experiments were performed. In experiment 1, the hearts were divided into the enteral lactoferrin (E-LF) 7.5 m, 15 m, 30 m, and 60 m groups, where lactoferrin (1000 mg/kg) was administered enterally 7.5, 15, 30, and 60 min, respectively, before perfusion; and a control group, where saline was administered 30 min before perfusion. In experiment 2, hearts were allocated to the perfusate lactoferrin (P-LF) 15 and 100 groups, where 15 mg/L and 100 mg/L lactoferrin were respectively added to the perfusate, and a control group. Each group was perfused for 20 min prior to 15 min of no-flow ischemia with pacing, followed by 20 min of reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (LV dP/dt max) 15 min after reperfusion. Myocardial phospho-protein kinase B (p-Akt) was assayed using western blotting. RESULTS: The LV dP/dt max 15 min after reperfusion in the E-LF 15 and 30 m groups was significantly higher than that in the control group. However, the effects disappeared in the E-LF 60 m group. In the second experiment, there were no significant differences in LV dP/dt max. Myocardial p-Akt was not significantly activated in any lactoferrin group. CONCLUSION: Cardioprotection was observed 15-30 min after enteral lactoferrin but not by direct cardiac perfusion with lactoferrin. Myocardial p-Akt was not associated with the cardioprotective effect. The cardioprotective effect may be induced by enteral lactoferrin-induced substances.

PI3K/Akt pathway mediates the positive inotropic effects of insulin in Langendorff-perfused rat hearts.

Insulin exerts positive inotropic effects on cardiac muscle; however, the relationship between cardiac contractility and phosphoinositol-3-kinase/Akt (PI3K/Akt) activation remains unclear. We hypothesized that the positive inotropic effects of insulin are dose-dependent and mediated via the PI3K/Akt pathway in isolated normal rat hearts. The Institutional Animal Investigation Committee approved the use of hearts excised from rats under pentobarbital anesthesia. The hearts were perfused at a constant pressure using the Langendorff technique. After stabilization (baseline), the hearts were randomly divided into the following four insulin (Ins) groups: 1) Ins0 (0 IU/L), 2) Ins0.5 (0.5 IU/L), 3) Ins5 (5 IU/L), and 4) Ins50 (50 IU/L) (n = 8 in each group). To clarify the role of the PI3K/Akt pathway in insulin-dependent inotropic effects, we also treated the insulin groups with the PI3K inhibitor wortmannin (InsW): 5) InsW0 (0 IU/L), 6) InsW0.5 (0.5 IU/L), 7) InsW5 (5 IU/L), and 8) InsW50 (50 IU/L). Hearts were perfused with Krebs-Henseleit buffer solution with or without wortmannin for 10 min, followed by 20 min perfusion with the solution containing each concentration of insulin. The data were recorded as the maximum left ventricular derivative of pressure development (LV dP/dt max). Myocardial p-Akt levels were measured at 3 min, 5 min, and at the end of the perfusion. In the Ins groups, LV dP/dt max in Ins5 and Ins50 increased by 14% and 48%, respectively, 3 min after insulin perfusion compared with the baseline. Tachyphylaxis was observed after 10 min in the Ins5 and Ins50 treatment groups. Wortmannin partially inhibited the positive inotropic effect of insulin; although insulin enhanced p-Akt levels at all time points compared with the control group, this increase was suppressed in the presence of wortmannin. The positive inotropic effect of insulin is dose-dependent and consistent with Akt activation. This effect mediated by high doses of insulin on cardiac tissue was temporary and caused tachyphylaxis, potentially triggered by Akt overactivation, which leads beta 1 deactivation.

Anesthetic experience does not reduce accidental dural puncture in surgical patients: a retrospective case-controlled study.

BACKGROUND: Accidental dural puncture (ADP), which is a complication of epidural anesthesia, still exists and leads to worse outcomes in surgical patients. While residency training is important for epidural competency, it remains unknown whether anesthetic experience reduces ADP in surgical patients. Using an incident reporting system along with anesthetic records, this case-controlled study retrospectively investigated risk factors associated with ADP in surgical patients. METHODS: Patients who experienced ADP during epidural anesthesia who were registered in the incident reporting system of our institution between April 2012 and March 2019 were enrolled. Patients with ADP were control-matched with those who without ADP in a 1:3 ratio, to compare the potential risk factors and calculated odds ratios (ORs) for ADP. The primary hypothesis was that anesthesiologists' experience reduces the incidence of ADP. The secondary hypothesis was that there are risk factors for ADP. Between-group differences in anesthesiologists' experience were compared using the Mann-Whitney U test. Significance was set at P < 0.05. RESULTS: Thirty-five patients who experienced ADP were identified from the incident reporting system. These were matched with 69 patients who did not experience ADP. There was no difference in the years of experience of anesthesiologists between the groups that did and did not experience ADP (8 [3-20] vs. 9 [3-18] years, respectively; P = 0.65). CONCLUSIONS: Having an experienced anesthesiologist did not guarantee the prevention of ADP. Daily individual training and briefings would be needed to reduce the incidence of ADP.

Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1.

Long-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

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.

Delayed awakening with apnea as a sign of cerebellar hemorrhage after vestibular schwannoma surgery: A case report.

Cerebellar hemorrhage after surgery is a rare but critical complication requiring prompt diagnosis and intervention. However, anesthetics can mask most brain compression signs. Prolonged coma with apnea after tumor resection under general anesthesia may indicate the need for prompt imaging to detect or exclude cerebellar lesions.

Short Sleep Duration on the Night Before Surgery Is Associated With Postoperative Cognitive Decline in Elderly Patients: A Prospective Cohort Study.

As the world is rapidly aging, and the number of elderly patients who undergo surgery is rising, postoperative cognitive decline among those patients has become an increasing healthcare problem. Although understanding the risk factors and mechanisms underlying the pathogenesis of postoperative cognitive decline is critically important from a preventative viewpoint, such knowledge and evidence are lacking. A growing body of evidence suggest an association between cognitive function and sleep duration. The purpose of this study was to investigate the association between postoperative cognitive function and sleep duration on the night before surgery using a wearable sleep tracker. In this 6-month prospective cohort study, we analyzed data from 194 patients aged ≥ 65 years who underwent elective non-cardiac and non-cranial surgery under general anesthesia. According to the sleep duration on the night before surgery, patients were categorized into following four groups: <5, 5-7, 7-9, and >9 h. Perioperative cognitive function and domains were assessed using a neuropsychological test battery, and the incidence and prevalence of cognitive decline over 6 months after surgery were analyzed using the multiple logistic regression analysis. During the 6-month follow-up period, 41 patients (21%) developed cognitive decline. The incidence of cognitive decline was significantly elevated for the patients with sleep duration < 5 h (vs. 7-9 h; surgical duration-adjusted odds ratio, 3.50; 95% confidence interval, 1.20-10.2; P < 0.05). The association between sleep duration and prevalence of cognitive decline was limited to the early postoperative period (at 1 week and 1 month). Among the cognitive domains assessed, attentional function was significantly impaired in patients with a sleep duration < 5 h [vs. 7-9 h at 1 week; 4/37 (10.8%) vs. 0/73 (0%); P < 0.05]. In conclusion, sleep duration < 5 h on the night before surgery was significantly associated with worse attentional function after surgery and higher incidence of cognitive decline. The present results indicate that sleep deprivation on the night before surgery may have a temporary but significantly negative influence on the patient's postoperative cognitive function and is a potential target for preventing cognitive decline.

Ulinastatin attenuates protamine-induced cardiotoxicity in rats by inhibiting tumor necrosis factor alpha.

Protamine causes cardiac depression, which may be mediated by tumor necrosis factor alpha (TNF-α). Ulinastatin, a human urinary protease inhibitor, inhibits TNF-α. Here, we aimed to investigate whether ulinastatin prevented protamine-induced myocardial depression by inhibiting TNF-α. Rat hearts were perfused using a Langendorff system, and three protocols were followed. Protocol 1: The hearts were divided into saline, ulinastatin-low, and ulinastatin-high groups. Protamine was administered to each group, and myocardial contractility was the primary outcome. Protocol 2: The hearts were allotted to saline or ulinastatin group. Protamine was administered to each group. TNF-α expression in the coronary effluent and myocardial tissue was measured. Protocol 3: The hearts were allotted to saline and ulinastatin groups. Recombinant rat-TNF-α was administered to each group. Protamine alone reduced the maximum left ventricular pressure derivative (LV dP/dt max) by 45 ± 4%. In contrast, the reduction in LV dP/dt max was 4 ± 3% in the ulinastatin-high group. Compared with that in the saline group, the increase in TNF-α in the coronary effluent was attenuated in the ulinastatin group. Recombinant TNF-α alone reduced LV dP/dt max (- 21 ± 14%). In contrast, when TNF-α was added in the presence of ulinastatin, the decrease in LV dP/dt max was prevented significantly (- 3 ± 8%). We showed, for the first time, that ulinastatin protected against protamine-induced myocardial damage, both by inhibiting TNF-α synthesis and by directly preventing the cardiodepressant action of TNF-α.

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.

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.

High-frequency jet ventilation during video-assisted thoracoscopic surgery in a patient with previous contralateral pneumonectomy.

A case of high-frequency jet ventilation (HFJV) during video-assisted thoracoscopic surgery (VATS) in a patient with previous contralateral pneumonectomy is presented. A 77-year-old man with a right pneumothorax was scheduled for bullectomy by VATS. He had undergone left pneumonectomy due to lung cancer 6 years earlier. Anesthesia was induced and maintained with propofol and fentanyl. The patient was intubated with a normal, single-lumen endotracheal tube (ETT). HFJV was applied through the ETT during the VATS procedure. Although PaCO(2) gradually increased from 51.9 mmHg to 80.0 mmHg, appropriate surgical conditions were provided, PaO(2) was well preserved, and blood pressure and heart rate were stable throughout the VATS procedure.