1 / 24

R3 성 준 경

Review Article (Anesthesiology 2009;110:408-21) Perioperative Glycemic Control An Evidence-based Review. R3 성 준 경. Hyperglycemia Risk factor for perioperative morbidity and mortality Intensive insulin theraphy(IIT) Target BG 80-110mg/dL cf) Standard therapy: target BG 180-200mg/dL

tracey
Download Presentation

R3 성 준 경

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Review Article (Anesthesiology 2009;110:408-21)PerioperativeGlycemic ControlAn Evidence-based Review R3 성 준 경

  2. Hyperglycemia • Risk factor for perioperative morbidity and mortality • Intensive insulin theraphy(IIT) • Target BG 80-110mg/dL • cf) Standard therapy: target BG 180-200mg/dL • 2001, Van den Berghe et al. - The first Leuven study • Randomized controlled trial(RCT) • More than 1500 surgical intensive care unit patients • Reduced hospital mortality by 34% • Significantly decresed morbidity, including blood stream infections, ARF, transfusions, and critical-illness polyneuropathy • Other studies concerning tight glycemic control • IIT during cardiac surgery significantly decreased infection rates and improved survival • Decreased allograft rejection • Improved outcome in the settings of acute neurologic injury and myocardial infarction

  3. Recent studies • Second Leuven study • Medical ICU patients may not benefit from IIT • High incidence of severe hypoglycemic events (BG<40mg/dL) • Intraoperative IIT during cardiac surgery may increase the incidence of death and stroke • Data are inconclusive • It is unclear if adequate evidence exists to support the widespread adoption of IIT • This review article’s intention • Summurize the pathophysiology and mechanism of hyperglycemia and insulin therapy • Review the evidence behind the use of IIT in the perioperative period (intraoperatively, postoperatively, and in the ICU)

  4. Materials and Methods • RCTs searched on MEDLINE and the Cochrane Library • Articles published between Jan 1, 1999 and Jan 31, 2009 • Terms searched: intenesive insulin, glycemic control, glucose control, hyperglycemia, intraoperative, intensive care, critically ill, and postoperative • Bibliographies of all relevant articles from the search were examined manually for additional articles • Searched ongoing trials from ClinicalTrials.gov

  5. Pathophysiology of Hyperglycemia • Stress-induced release of counterregulatory hormones: cortisol, glucagon, epinephrine, and growth hormone • Upregulation in hepatic gluconeogenesis, and glycogenolysis • Compromised insulin-regulated peripheral glucose uptake (primarily due to defect in the glucose a defect in the glucose transporter-4, GLUT4) • Deleterious effects of hyperglycemia • Impaired neutrophilchemotaxis and phagocytosis • Decreased complement function • Decreased vasodilation • Impaired reactive endothelial nitric oxide generation • Increased expression of leukocyte and endothelial adhesion molecules • Increased cytokine levels  inflammation, vulnerability to infection, multiorgan system dysfunction

  6. Pathophysiology of Hyperglycemia • Intensive insulin therapy • Decrease circulating levels of ICAM-1 and E-selectin  reduces endothelial activation • Protect hepatocyte mitochondrial ultrastructure • Stimulate peripheral glucose uptake by increasing transcription of GLUT-4 and hexokinase • Normalize C-peptide and circulating adiponectin levels • Improve serum lipid profile by increasing LDL and HDL levels while decreasing serum TG

  7. Pathophysiology of Hyperglycemia • Proinflammatory cytokines (TNF-a)  causes lung & renal injury • High circulatory level in hyperglycemic patients • Relationship between inflammatory cytokines and glucose metabolism is complex • Increased cytokines  increased insulin resistance  hyperglycemia • Sepsis patients often require higher doses of insulin • Result of achieving normoglycemia or due to insulin effect? • Due to control of glucose levels • However, insulin dose was an independent negative factor • Detrimental effects of hypoglycemia • Causes neuronal necrosis • Increased secretion of glucagon, epinephrine, growth hormone, and cortisol • Seizure, coma or even death in long term ICU staying DM patients

  8. Effects of IIT by Patient Population- The Critically Ill

  9. - The Critically Ill

  10. - Intraoperative IIT • Prospective randomized trials of intraoperative glucose-insulin-potassium (target BG 125-200) or standard tx (BG<250) • Rationale for using glucose-insulin-potassium mixture • Cardioprotective effects • Unable to assess the relationship between hyperglycemia and morbidity and mortality • Furnary et al. – before and after study of intraoperative subcutaneous insulin vs. continuous insulin infusion (target BG changed during study period: 150-200  125-175  100-150) • 3,554 diabetic patients undergoing CABG • 57% reduction in mortality • Limitations • Nonrandomized • Changes in the protocol • Potential for temopral bias due to a 14-yr study period

  11. - Intraoperative IIT • More recent before-after study – intraop IIT (target BG 150-200) followed by postop IIT (target BG <140) in diabetic patients undergoing surgical myocardial revascularization • Reduced mortality by 72% • Ouattara et al. • Poor intraop glycemic control • Severe in-hospital morbidity in diabetic cardiac surgery patients • Prospective, randomized trial of glucose-insulin-potassium initiated intraoperatively with a target BG of 125-200 compared to standard therapy (target BG < 250) in diabetic CABGpatients • Survival advantage • Decreased length of stay • Decreased wound infection rates • Limitations • Lack of blinding and potential undertreatment in the standard therapy

  12. - Intraoperative IIT • Gadhi et al. – single center RCT of both diabetic and nondiabetic patients undergoing CABG compared intraop IIT (target BG 80-100) with conventional tx (target BG <200) • Showed no reduction in perioperative morbidity and mortality • Significant increase in the incidence of stroke in the IIT group and a trend toward increased mortality • Notably, diabetic patients in this study did not achieve BG goals • Data on intraoperative glucose control in noncardiac surgical patients is lacking

  13. - Postoperative IIT • Analysis of 1585 diabetic patients undergoing cardiac suregry before and after the implementation of an insulin protocol (target BG <200) • Significantly decreased incidence of deep wound infection (2.4%  1.5%) • Furnary et al. – prospective study of 2467 patients with the same BG goal • IIT was associated with 66% decrease in deep sternal wound infection • Golden et al. – retrospective analysis • Postoperative hyperglycemia was an independent predictor of infectious complications in diabetic patients undergoing CABG

  14. - Postoperative IIT • Studies on the effect of postoperative hyperglycemia outside of the diabetic cardiac surgery population are lacking • Vriesendorp et al. - retrospective study • Infrainguinal vascular surgery • Hyperglycemia is independent risk factor for infection • Prospective randomized pilot trial comparing IIT (target BG 80-120) to conventional tx (target BG 80-220) • Anerysmal SAH status after surgical clipping • Decreased infection rate (4227%) • No difference in the incidence of vasospasm, neurologic outcome, or mortality • The frequent use of intraoperative dexamethasone • Further increases glucose level • Could make postoperative glycemic control harder to achieve

  15. - Obstetrical IIT • Focused on gestational and pregestational diabetes • The American College of Obstetricians and Gynecologists currently recommends a BG target of less than 110 mg/dL during labor and delivery • Avoid intrapartum maternal hyper glycemia  avoid fetal hyperglycemia  avoid subsequent neonatal hypoglycemia • Maintaining maternal BG below the diabetic range throughout pregnancy may be equally important

  16. - Diabetics versus Nondiabetics • No prospective study has specifically compared the differing effects of IIT on diabetic vs. nondiabetic patients • Regarding critically ill population, some studies showed no difference in mortality among diabetic patients • Small number of patients • Target BG not reached • Some studies’ result suggests that ideal glucose levels for critically ill patients may differ by diabetic status • Different benefits of IIT between Type I DM and Type II DM • Unclear • Type II generally requires higher dose of insulin • Higher requirement of insulin is a negative predictor • Regardless of BG level, it is likely that the two groups will differ in their response to IIT

  17. Appropriate Glucose Targets • Controversy exists regarding appropriate BG targets, particularly because aggressive glycemic control targets are associated with increased risk of hypoglycemic events • Many studies shows significantly improved outcomes in tight glucose control • However, there are insufficient data to determine the optimal SD in BG

  18. Measurement of Blood Glucose • There is controversy over how and when to measure BG • Discrepancy existed between BG measuring techniques from laboratory results • Chemical analysis of arterial blood gas • Glucometeranalysis of capillary blood by fingerstick • Glucometer analysis of arterial blood • Especially during hypoglycemia • Errors tended to overestimate BG levels • Peripheral hypoperfusion, certain drugs, anemia, elevated bilirubin or uric acid all affected BG measurements • Wide variation of BG indeces • Admission glucose, max daily glucose, mean morning glucose, mean overall glucose, etc. • BG level varies – significantly lower in morning

  19. Implementation of IIT Protocols • The method of insulin administration and measurement, frequency of BG checks, and protocol design vary widely among the studies • Although some studies report ease in achieving normoglycemia, others report BG values within target range as little as 40% of the time • We successfully implemented an IIT protocol at the University of California, San Francisco (UCSF) Medical Center in December 2002 • UCSF is a 600-bed academic hospital with 60 medical, surgical, cardiac, and neuroscience ICU beds and a typical ICU nurse-to-patient ratio of 1:1.5 • The IIT protocol aimed to achieve a target BG between 80 and 120 mg/dL via adjustment in insulin dosing by 0.2–3.0 units per hour based on both the absolute value and trajectory of glucose concentration

  20. Implementation of IIT Protocols • In our opinion, the most important steps in safely implementing an effective IIT protocol are pilot testing and stepwise implementation, which allow rapid response to problems with the protocol • Using these tools, we were able to achieve good glycemic control (median BG, 119 mg/dL) with hypoglycemia (defined as BG 60 mg/dL) rate of 0.08%

  21. Cost-Effectiveness • Furnary et al. • Showed decreased costs when IIT was used in diabetic CABG patients • Krinsley and Jones (mixed medical-surgical ICU) • showed a decrease in ICU and hospital LOS, ventilator days, and laboratory, pharmacy, and radiology costs, accounting for a total decrease in treatment costs of $1580 per patient • Van den Berghe et al. • decreased cost of 2638 euros ($4172) in a surgical ICU population receiving IIT • Recent studies showing no mortality benefit and increased incidence of hypoglycemia and serious adverse events are unlikely to demonstrate cost-effectiveness

  22. Future Directions • Controversy regarding the safety and efficacy of IIT exists, and additional RCTs are needed before definitive recommendations can be made • Large scale RCTs are still being conducted (6105 patients) • Advancement in technologies • Continuous subcutaneous glucose monitoring • Automation of the insulin infusion • Evaluation is underway • The ultimate goal of these technological advances is the creation of closed-loop glucose control. A closed-loop system couples continuous glucose monitoring with an IIT algorithm and an automatic intravenous infusion pump, thereby acting like an artificial pancreas

  23. Conclusion • Although it is clear that hyperglycemia is harmful, there is currently insufficient evidence to support the routine use of tight glycemic control (target BG 80–110mg/dL) in the operating room or the ICU • With careful, stepwise implementation of IIT protocols, maintaining BG less than 150 mg/dL and reducing BG variability may be both safe and effective • It is likely that there are subpopulations of patients that would benefit from tighter glycemic control (BG 80–110 mg/dL). Until these populations are identified, however, the newly elucidated risk of hypoglycemia and serious adverse events cannot be ignored

  24. Conclusion • Perhaps more importantly, the experience with immediate and widespread acceptance of IIT after the publication of only one incompletely blinded single-center study suggests that we may need to redefine the idea of evidence-based medicine and be more hesitant to change the standard of care • The controversy over perioperative beta blockade substantiates this idea; the use of beta-blockers in at-risk patients in the perioperative period was enthusiastically adopted after two studies showed benefit, but preliminary results from the PeriOperative Ischemic Evaluation (POISE) trial show an increase in the risk of death and stroke in the treatment group

More Related