Boris Mraovic

Hyperglycemia Prevents Isoflurane-induced Preconditioning against Myocardial Infarction

Background Volatile anesthetics stimulate but hyperglycemia attenuates activity of mitochondrial adenosine triphosphate–regulated potassium channels. The authors tested the hypothesis that acute hyperglycemia interferes with isoflurane-induced preconditioning in vivo. Methods Barbiturate-anesthetized dogs (n = 79) were instrumented for measurement of hemodynamics. Myocardial infarct size and collateral blood flow were assessed with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of normal saline (normoglycemic controls) or 15% dextrose in water to increase blood glucose concentrations to 300 or 600 mg/dl in the absence or presence of isoflurane (0.5 or 1.0 minimum alveolar concentration [MAC]) in separate experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion. Results Myocardial infarct size was 26 ± 1% of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 ± 2 and 13 ± 1% during 0.5 and 1.0 MAC, respectively). Hyperglycemia alone did not alter infarct size (26 ± 2 and 33 ± 4% during 300 and 600 mg/dl, respectively). Moderate hyperglycemia blocked the protective effects of 0.5 MAC (25 ± 2%) but not 1.0 MAC isoflurane (13 ± 2%). In contrast, severe hyperglycemia prevented reductions of infarct size during both 0.5 MAC (29 ± 3%) and 1.0 MAC isoflurane (28 ± 4%). Conclusions Acute hyperglycemia attenuates reductions in myocardial infarct size produced by isoflurane in dogs.

Is isoflurane-induced preconditioning dose related?

Background Volatile anesthetics precondition against myocardial infarction, but it is unknown whether this beneficial action is threshold- or dose-dependent. The authors tested the hypothesis that isoflurane decreases myocardial infarct size in a dose-dependent fashion in vivo. Methods Barbiturate-anesthetized dogs (n = 40) were instrumented for measurement of systemic hemodynamics including aortic and left ventricular pressures and rate of increase of left ventricular pressure. Dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive either 0.0, 0.25, 0.5, 1.0, or 1.25 minimum alveolar concentration (MAC) isoflurane in separate groups. Isoflurane was administered for 30 min and discontinued 30 min before left anterior descending coronary artery occlusion. Results Infarct size (triphenyltetrazolium staining) was 29 ± 2% of the area at risk in control experiments (0.0 MAC). Isoflurane produced significant (P < 0.05) reductions of infarct size (17 ± 3, 13 ± 1, 14 ± 2, and 11 ± 1% of the area at risk during 0.25, 0.5, 1.0, and 1.25 MAC, respectively). Infarct size was inversely related to coronary collateral blood flow (radioactive microspheres) in control experiments and during low (0.25 or 0.5 MAC) but not higher concentrations of isoflurane. Isoflurane shifted the linear regression relation between infarct size and collateral perfusion downward (indicating cardioprotection) in a dose-dependent fashion. Conclusions Concentrations of isoflurane as low as 0.25 MAC are sufficient to precondition myocardium against infarction. High concentrations of isoflurane may have greater efficacy to protect myocardium during conditions of low coronary collateral blood flow.

Chronic Hyperglycemia Attenuates Coronary Collateral Development and Impairs Proliferative Properties of Myocardial Interstitial Fluid by Production of Angiostatin

Background—Development of coronary collateral vessels is impaired in patients with diabetes mellitus. We tested the hypothesis that hyperglycemia alone attenuates collateral development and abolishes proliferative properties of myocardial interstitial fluid (MIF) by enhancing expression of matrix metalloproteinases (MMP) and angiostatin. Methods and Results—Chronically instrumented dogs were randomly assigned to receive an infusion of normal saline (control; n=9) or 70% dextrose in water to increase blood glucose to 350 to 400 mg/dL for 8 h/d (hyperglycemia; n=7) in the presence or absence (sham; n=9) of brief (2 minutes), repetitive coronary artery occlusions (1/h; 8/d for 21 days). Collateral perfusion increased to 41±11% and 49±6% of normal zone flow in control dogs on days 14 and 21 (P <0.05) but remained unchanged over 21 days in hyperglycemic and sham dogs (12±3% and 13±3%, respectively). A progressive reduction of the postocclusive peak reactive hyperemic response was also observed in control dogs (16±1 to 10±1 Hz · 102 on days 1 and 21, respectively) but not in hyperglycemic (17±2 to 20±2) or sham (17±2 to 16±1) dogs. Endothelial cell tube formation was produced by MIF obtained from control dogs but not hyperglycemic or sham dogs. Coincubation of MIF from hyperglycemic dogs with an angiostatin antibody restored endothelial cell tube formation. MMP-9 activity and expression of angiostatin were increased in dogs receiving exogenous glucose compared with controls Conclusions—Chronic hyperglycemia abolishes development of coronary collateral vessels by increasing MMP-9 activity and angiostatin expression in dogs.

Preadmission Hyperglycemia is an Independent Risk Factor for In-Hospital Symptomatic Pulmonary Embolism After Major Orthopedic Surgery

We investigate whether preadmission hyperglycemia is a risk factor for developing in-hospital symptomatic pulmonary embolism after major orthopedic surgery. Medical records of patients undergoing total hip or total knee arthroplasty from January 2001 to April 2006 were reviewed. The incidence of PE was 1.47% (107/7282 patients). Multivariate analysis showed that preadmission blood glucose (BG) of at least 200 mg/dL independently increased the risk of pulmonary embolism by 3.19 times (P = .015), when compared with patients with BG of less than 110 mg/dL. Other significant risks factors were age (>or=70 years old), body mass index of more than 30 kg/m(2), and congestive heart failure. Total knee had 2.19 times (P = .002) more risk than total hip arthroplasty and bilateral procedure increased the risk by 2.13 times (P = .015). Sex, American Society of Anesthesiologists status, duration of surgery, malignancy, pulmonary disease, hypertension, diabetes mellitus, dyslipidemia, sleep apnea, and stroke were not found to be significant risk factors for pulmonary embolism.

Clinical need for continuous glucose monitoring in the hospital.

Automation and standardization of the glucose measurement process have the potential to greatly improve glycemic control, clinical outcome, and safety while reducing cost. The resources required to monitor glycemia in hospitalized patients have thus far limited the implementation of intensive glucose management to patients in critical care units. Numerous available and up-and-coming technologies are targeted for the hospital patient population. Advantages and limitations of these devices are discussed herewith in.

Patients With Uncontrolled Components of Metabolic Syndrome Have Increased Risk of Complications Following Total Joint Arthroplasty

Metabolic syndrome (MetS)-a diagnostic grouping of diabetes, dyslipidemia, hypertension, and obesity-has been indicated as a risk factor for perioperative complications following total joint arthroplasty (TJA). This study investigates the impact of MetS on perioperative complications, specifically the importance of controlling MetS components. One hundred thirty-three patients undergoing TJA with all four components of MetS were identified. They were matched one-to-one with patients without MetS. Control of diabetes, dyslipidemia, and hypertension was assessed. Thirty-five patients with MetS were found to have at least a single uncontrolled component. The complication rates were 49%, 8%, and 8% for uncontrolled MetS, controlled MetS, and no MetS, respectively. Multivariate analysis confirmed independent associations between control of MetS components and both perioperative complications and length of stay. Both surgeons and patients should be aware of the substantial risk of dangerous complications following TJA in patients with uncontrolled metabolic syndrome.

The dose-response of nitrous oxide in postoperative nausea in patients undergoing gynecologic laparoscopic surgery: a preliminary study.

BACKGROUND:Whether nitrous oxide (N2O) increases the incidence of postoperative nausea and vomiting (PONV) after laparoscopic gynecologic surgery is still controversial, which may be due to the administration of different concentrations of inspired N2O. We investigated whether N2O results in a dose–response increase in PONV. METHODS:Patients undergoing gynecologic laparoscopic surgery were randomized to receive 30% oxygen with air (G0, n = 46), 50% N2O with oxygen (G50, n = 46), or 70% N2O with oxygen (G70, n = 45). A standardized general anesthetic was used with no PONV prophylaxis. Known risk factors for PONV were controlled. Metoclopramide was used as a rescue antiemetic. The incidence of nausea, vomiting, use of rescue antiemetic, and pain visual analog scale (VAS) score was measured at 2 and 24 h postoperatively. RESULTS:Patient demographics were comparable, and there were no differences among groups regarding factors that may influence PONV. The incidence of PONV at 24 h was 33% (15 of 46) in the G0 group, 46% (21 of 46) in the G50 group, and 62% (28 of 45) in the G70 group (P = 0.018). Subgroup analysis revealed a difference between G0 versus G70 groups (P = 0.018), but no significant difference between G0 versus G50 groups and G50 versus G70 groups. The incidence of nausea showed a similar difference (G0 = 26%, G50 = 35%, and G70 = 56%; P = 0.012), but the incidence of vomiting was not different among the groups although there was a trend (G0 = 28%, G50 = 35%, and G70 = 42%; P = 0.377). The severity of nausea (measured by VAS 100 mm) was significantly increased with increasing N2O concentration (G0 = 10.9, G50 = 12.7, and G70 = 20.5; P = 0.027). The highest VAS score during 24 h was used for the analysis. There was no difference in the use of a rescue antiemetic among groups. Pain VAS scores and opioids consumption were not different among groups (at 2 and 24 h after surgery). CONCLUSIONS:N2O increases the incidence of postoperative nausea after gynecologic laparoscopic surgery. This preliminary finding indicates that N2O may increase PONV in a dose-dependent fashion. A study with a sample size of >400 patients in each group would be necessary to demonstrate a statistically significant difference among each of these three groups. We do not recommend using a high concentration of N2O in this clinical setting.

The Role of Mitochondrial and Sarcolemmal KATP Channels in Canine Ethanol-Induced Preconditioning In Vivo

Chronic consumption of small doses of ethanol protects myocardium from ischemic injury. We tested the hypothesis that mitochondrial and sarcolem-mal adenosine triphosphate-dependent potassium (KATP) channels mediate these beneficial effects. Dogs (n = 76) were fed with ethanol (1.5 g/kg) or water mixed with dry food bid for 6 or 12 wk, fasted overnight before experimentation, and instrumented for measurement of hemodynamics. Dogs received intracoronary saline (vehicle), 5-hydroxydecano-ate (a mitochondrial KATP channel antagonist; 6.75 mg/kg over 45 min), or HMR-1098 (a sarcolemmal KATP channel antagonist; 45 &mgr;g/kg over 45 min) and were subjected to a 60 min coronary artery occlusion followed by 3 h of reperfusion. A final group of dogs was pretreated with ethanol and chow for 6 wk before occlusion and reperfusion. Myocardial infarct size and transmural coronary collateral blood flow were measured with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. The area at risk of infarction was similar between groups. A 12-wk pretreatment with ethanol significantly reduced infarct size to 13% ± 2% (mean ± sem;n = 8) of the area at risk compared with control experiments (25% ± 2%;n = 8), but a 6-wk pretreatment did not (21% ± 2%;n = 8). 5-hydroxydecanoate and HMR-1098 abolished the protective effects of 12-wk ethanol pretreatment (24% ± 2% and 29% ± 3%, respectively;n = 8 for each group) but had no effect in dogs that did not receive ethanol (22% ± 2% and 23% ± 4%, respectively;n = 8 for each group). No differences in hemodynamics or transmural coronary collateral blood flow were observed between the groups. The results indicate that mitochondrial and sarcolemmal KATP channels mediate ethanol-induced preconditioning in dogs independent of alterations in systemic hemodynamics or coronary collateral blood flow.

Analysis: Continuous Glucose Monitoring during Intensive Insulin Therapy

Results of the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial, intensive insulin therapy (IIT), and use of a continuous glucose sensor in intensive care units (ICU) were analyzed. The NICE-SUGAR trial was unable to determine if optimal intensive insulin therapy decreases mortality. Continuous glucose monitoring (CGM) technology has the potential to improve glycemic control with low glucose variability and low incidence of hypoglycemia. Interstitial fluid CGM may not be useful in perioperative and ICU settings. Studies evaluating the accuracy and reliability of CGM devices, based on a whole blood sample in perioperative and ICU settings, are needed. Once a reliable CGM sensor for ICU use is identified, a large, prospective, controlled, multicenter study could determine if optimal IIT with a low or zero incidence of hypoglycemic events improves mortality.:

Intraoperative Accuracy of a Point-of-Care Glucose Meter Compared with Simultaneous Central Laboratory Measurements

Background: Concerns have been raised about the use of point-of-care (POC) glucose meters in the hospital setting. Accuracy has been questioned especially in critically ill patients. Although commonly used in intensive care units and operating rooms, POC meters were not approved by the Food and Drug Administration for such use. Data on POC glucose meter performance during anesthesia are lacking. We evaluated accuracy of a POC meter in the intraoperative setting. Methods: We retrospectively reviewed 4,333 intraoperative records in which at least one intraoperative glucose was measured using electronic medical records at a large academic hospital. We evaluated the accuracy of a POC glucose meter (ACCU-CHEK® Inform, Roche Pharmaceuticals) based on the 176 simultaneous central laboratory (CL) blood glucose (BG) measurements that were found (i.e., documented collection times within 5 minutes). Point-of-care and central lab BG differences were analyzed by Bland-Altman and revised error grid analysis (rEGA). Results: Mean POC BG was 163.4 ± 64.7 mg/dl [minimum (min) 48 mg/dl, maximum (max) 537 mg/dl] and mean CL BG was 162.6 ± 65.1 mg/dl (min 44 mg/dl, max 502 mg/dl). Mean absolute difference between POC and CL BG was 24.3 mg/dl. Mean absolute relative difference was 16.5% with standard deviation 26.4%. Point-of-care measurements showed a bias of 0.8 relative to the corresponding CL value, with a precision of 39.0 mg/dl. Forty (23%) POC BG values fell outside the Clinical and Laboratory Standards Institute guideline and 3.4% POC measurements fell in zones C and D of the rEGA plot. Conclusions: The tested POC glucose meter performed poorly compared to a CL analyzer intraoperatively. Perioperative clinicians should be aware of limitations of specific POC glucose meters, and routine use of POC glucose meters as sole measurement devices in the intraoperative period should be carefully considered.