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Hyperglycemia in the Intensive Care Unit Yoğun Bakım Ünitesinde Hiperglisemi

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Hyperglycemia in the Intensive Care Unit Yoğun Bakım Ünitesinde Hiperglisemi Journal of the Turkish Society of Intensive Care (2014)12: 67-71 DOI: 10.4274/tybdd.03521 REVIEW / DERLEME Rainer Lenhardt, Ozan Akca Hyperglycemia in the Intensive Care Unit Yoğun Bakım Ünitesinde Hiperglisemi SUMMARY Hyperglycemia is frequently The goal of this review was to give a Received/Geliş Tarihi : 23.12.2014 Accepted/Kabul Tarihi : 13.01.2015 encountered in the intensive care unit. In brief overview about pathophysiology of Journal of the Turkish Society of Intensive Care, published this disease, after severe injury and during hyperglycemia and to summarize current by Galenos Publishing diabetes mellitus homeostasis is impaired; guidelines for glycemic control in critically ill Türk Yo€un Bak›m Derneği Dergisi, Galenos Yay›nevi taraf›ndan bas›lm›flt›r. hyperglycemia, hypoglycemia and glycemic patients. ISSN: 2146-6416 variability may ensue. These three states Key Words: Hyperglycemia, blood glucose have been shown to independently increase control, intensive care unit mortality and morbidity. Patients with ÖZET Yoğun bakım ünitesinde diabetics admitted to the intensive care unit hiperglisemiye sıklıkla rastlanmaktadır. tolerate higher blood glucose values without Rainer Lenhardt, Ozan Akca, Hastalık durumlarında ağır hasar sonrasında increase of mortality. Stress hyperglycemia University of Louisville, Department of ve diyabetes mellitus sürecinde homeostaz Anesthesiology and Perioperative Medicine, may occur in patients with or without Louisville, USA bozulur, hiperglisemi, hipoglisemi ve diabetes and has a strong association with glisemik değişkenlik meydana gelebilir. Bu Rainer Lenhardt M.D. (✉), increased mortality in the intensive care unit üç durumun bağımsız olarak mortalite ve University of Louisville, Department of patients. Insulin is the drug of choice to treat morbiditeyi artırdığı gösterilmiştir. Stres Anesthesiology and Perioperative Medicine, hyperglycemia in the intensive care unit. Louisville, USA hiperglisemisi diyabetik veya diyabetik In patients with moderate hyperglycemia olmayan hastalarda görülebilir ve yoğun a basal–bolus insulin concept can be used. bakım hastalarındaki artmış mortaliteyle Close glucose monitoring is of paramount güçlü ilişkiye sahiptir. Yoğun bakım importance throughout the intensive care ünitesinde hiperglisemi tedavisinde E-mail: [email protected] unit stay of the patient. In the guidelines for tercih edilen ilaç insülindir. Orta derecede Phone: +90 001 502-852-5851 glycemic control based on meta-analyses hiperglisemisi olan hastalarda, bazal- it was shown that a tight glycemic control bolus insülin uygulaması kullanılabilir. does not have a significant mortality Metaanalizlere dayanan glisemik kontrol advantage over conventional treatment. kılavuzlarında sıkı glisemik kontrolün konvansiyonel tedaviye kıyasla mortalitede Given the controversy about optimal blood anlamlı fayda sağlamadığı gösterilmiştir. glucose goals in the intensive care unit Yoğun bakım ünitesindeki kan glukoz setting, it seems reasonable to target a blood hedefleri tartışmalı olmakla birlikte 140 glucose level around 140 mg/dL to avoid mg/dl civarında kan glukozu, hipoglisemi episodes of hypoglycemia and minimize ataklarından kaçınmak ve glisemik glycemic variability. The closed loop system değişkenliği en aza indirmek kabul edilebilir with continuous glucose monitoring and hedeflerdir. Bu derlemede hipergliseminin algorithm based insulin application by an patofizyolojisine genel bir bakış yapılması ve infusion pump is a promising new concept kritik hastalardaki glisemik kontrol için son with the potential to further reduce mortality kılavuzların özetlenmesi amaçlanmıştır. and morbidity due to hyperglycemia, Anah tar Ke li me ler: Hiperglisemi, kan glukoz hypoglycemia and glycemic variability. kontrolü, yoğun bakım 68 Introduction Initial stress provokes an increase in catecholamine, cortisol, glucagon and growth hormone secretions resulting in Hyperglycemia is encountered frequently in the intensive excessive hepatic glycogenolysis and gluconeogenesis and care unit (ICU) setting. Hyperglycemia may be due to pre- insulin resistance. The resulting hyperglycemia induces an existing and known diabetes. It can also be seen in patients increase in pro-inflammatory cytokine production, including who were unaware of having diabetes. In Turkey, diabetes IL-1, IL-6 and TNF-alpha (9). Pro-inflammatory cytokines, in has a prevalence of about 7.3%. turn, may alter insulin receptor signaling thereby increasing In addition, hyperglycemia can be observed in patients insulin resistance. who are not diabetics, but have an increased resistance to Hyperglycemia can be seen as adaptive response to injury or insulin due to stress of injury or critical illness. This is termed critical illness. Glucose is delivered to vital tissues such as brain stress hyperglycemia. Combinations of stress hyperglycemia and blood cells, while glucose uptake is diminished in insulin and diabetes do occur and can raise blood glucose values dependent tissues such as skeletal muscle and fatty tissues. even further. However, sustained hyperglycemia causes an increase of Hyperglycemia in the critical care unit has been radical oxygen species (ROS) with subsequent mitochondrial associated with increased morbidity and mortality. In early dysfunction (10). The mitochondrial dysfunction and change randomized controlled trials, strict normoglycemia (80-110 in ultrastructure is thought to be a culprit of organ dysfunction mg/dl) by use of insulin infusions has shown a reduction in and may contribute to an increase of mortality associated morbidity and mortality (1,2). However, these results could with stress hyperglycemia (11). not be reproduced in later multicenter trial (3). A recent meta- Hyperglycemia also induces changes in blood coagulation, analysis revealed that tight glycemic control does not have a immune cell function and wound healing (12). On a cellular mortality advantage over a less stringent glycemic control in level, hyperglycemia triggers endothelial dysfunction ICU patients (4). inhibiting nitric oxide production. Monocytes exert enhanced Various speculations have nurtured theories about cytokine production under the influence of hyperglycemia the discrepancy in patient outcomes between the older as do macrophages. In addition, hyperglycemia augments and the later studies. One possible explanation may lie in macrophage proliferation and activity and induces neutrophil the significantly higher incidence of severe (<40 mg/dl) dysfunction. Lastly, hyperglycemia inhibits T cell proliferation hypoglycemic events in patients undergoing tight glycemic and blocks neutrophil tissue infiltration, all of which can lead control. Griesdale showed in his meta-analysis that to impaired wound healing (13). hypoglycemia was six times more likely to occur during tight glycemic control compared with conventional glucose control (5). Domains of Glycemic Control Glycemic variability is considered yet another domain of glycemic control besides hyper-and hypoglycemia. There Under normal conditions glycemic homeostasis is is an independent association between glycemic variability tightly controlled. In disease states or after severe injury and mortality in critically ill patients according to various and during diabetes mellitus homeostasis is impaired and observational studies (6-8). hyperglycemia, hypoglycemia and glycemic variability can The goal of this review is to give a brief overview about ensue. These three domains of glycemic control have been pathophysiology of hyperglycemia, address the three domains associated independently with increased risk of death in of glycemic control and summarize current guidelines for critically ill patients. Underlying diabetes may modulate the glycemic control in critically ill patients. relation of the three domains of glycemic control in this patient population. Pathophysiology Hyperglycemia Hyperglycemia occurs as main laboratory aberration in diabetes mellitus type-1 and type-2 and during gestational Diabetes has been defined as a fasting plasma glucose diabetes. Type-1 diabetes is defined by insufficient insulin of >126 mg/dl and a casual plasma glucose concentration production due to a ß-cell disorder. In contrast, the etiology of of >200 mg/dl or a 2 hour plasma glucose >200 mg/dl after type-2 diabetes is a combination of ß-cell defects and insulin oral glucose tolerance test (14). Likewise, a hemoglobin A1C resistance. of >6% can be classified as diabetes mellitus (15). Diabetics Acute, sustained hyperglycemia can be triggered by critical mainly suffer from long term sequelae including an increased illness or severe trauma, also termed stress hyperglycemia. risk of myocardial infarction, stroke, nephropathy, foot ulcer, The development of stress hyperglycemia is a result of an retinopathy and neuropathy. Of note, it has been shown imbalance between insulin and counter-regulatory hormones. that patients with known diabetes have a lower mortality 69 during critical illness compared to patients with previously In a recent large retrospective analysis of prospectively undiagnosed diabetes (16). collected data Krinsley et al. have demonstrated slightly Hyperglycemia due to stress from severe disease or different nadirs of blood glucose values associated with trauma has been defined as plasma glucose levels of >140 lowest mortality (31). mg/dl (17). Stress hyperglycemia can occur in diabetic and Non-diabetic patients in the ICU appeared to have non-diabetic patients alike and has a strong association
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