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作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　March 25, 2010 — 根據發表於3月份Mayo Clinic Proceedings期刊的研究結果，即使是輕微或中度的低血糖也與重症患者的死亡率有關。
　　
　　第二作者、澳洲Victoria Heidelberg Austin Health的Rinaldo Bellomo醫師在新聞稿中表示，即使在發生低血糖時調整胰島素治療，低血糖越嚴重者，死亡風險越大。
　　
　　研究目標是評估重症患者輕微或中度低血糖和死亡率風險增加之間是否有獨立關聯。
　　
　　從2000年1月1日至2004年10月14日，共有4,946名病患住院墨爾本和雪梨的兩個醫院加護病房(ICUs)，研究者檢視低血糖(定義為血糖濃度低於81 mg/dL)的獨立關聯，以及這些人之中，發生至少1次低血糖的1,109人的結果。
　　
　　這1,109位的醫院死亡率為36.6%，無低血糖的3,837名對照組為19.7% (P < .001)，最低血糖值介於72-81 mg/dL者的未校正死亡率比對照組高(25.9% vs 19.7%；未校正勝算比[OR]為1.42；95%信心區間[CI]為1.12 - 1.80；P = .004)。
　　
　　Bellomo醫師表示，校正其他風險因素之後，死亡風險依舊較高，因此認為低血糖與此風險增加有獨立關聯。
　　
　　低血糖嚴重度增加與死亡率顯著增加有關(P < .001)，校正胰島素治療之後，低血糖與死亡風險、心血管死亡、感染症死亡等有獨立關聯。
　　
　　Bellomo醫師表示，我們的結果認為，加護病房醫師不可以忽視輕微到中度低血糖情況，在這方面，於加護病房使用連續血糖監測等新技術，有助於避免低血糖或者可及早確認有此情況。
　　
　　研究限制包括屬於回溯設計、可能有系統性誤差和偏見；屬於觀察型設計，無法確認因果關係；只有在兩個病房進行，無法一般化。
　　
　　研究作者寫道，對於重症病患，輕微或中度低血糖和死亡之間有所關聯，即使在發生低血糖時調整胰島素治療之後，低血糖越嚴重者，死亡風險越大。
　　
　　史丹佛醫院的James S. Krinsley醫師以及梅約診所的Mark T. Keegan醫師在編輯評論中表示，連續或準連續血糖監測儀器、封閉迴路血糖控制系統的發展和臨床應用，將會有所幫助。
　　
　　Krinsley醫師和Keegan醫師寫道，藉由使用這些新科技，加上演算導向治療協定，將可大幅減少低血糖比率；再者，進行研究前瞻評估將減少血糖變動是為治療目標時的潛在助益，屆時，可確認Egi等人研究提出的，低血糖、特別是嚴重低血糖，對於重症病患有害；需強調此臨床問題的複雜性；強調醫師控制血糖的實務原則首重安全性。
　　
　　Austin醫院加護病房信託基金支持本研究。  


Even Mild or Moderate Hypoglycemia Linked to Mortality in Critically Ill Patients

By Laurie Barclay, MD
Medscape Medical News

March 25, 2010 — Even mild or moderate hypoglycemia is linked to mortality in critically ill patients, according to the results of a study reported in the March issue of Mayo Clinic Proceedings.

"Even after adjustment for insulin therapy or timing of hypoglycemic episode, the more severe the hypoglycemia, the greater the risk of death," said second author Rinaldo Bellomo, MD, from Austin Health in Heidelberg, Victoria, Australia, in a news release.

The goal of the study was to evaluate whether there is an independent association between mild or moderate hypoglycemia in critically ill patients and an increased risk for mortality.

From January 1, 2000, to October 14, 2004, a total of 4946 patients were admitted to 2 hospital intensive care units (ICUs) in Melbourne and Sydney, Australia. The investigators examined the independent association between hypoglycemia, defined as a glucose concentration of less than 81 mg/dL, and outcome in 1109 of these patients who had at least 1 episode of hypoglycemia.

Hospital mortality rate was 36.6% in these 1109 patients vs 19.7% in the 3837 nonhypoglycemic control patients (P < .001). Unadjusted mortality rate was greater in patients with a minimum blood glucose concentration between 72 and 81 mg/dL vs control patients (25.9% vs 19.7%; unadjusted odds ratio [OR], 1.42; 95% confidence interval [CI], 1.12 - 1.80; P = .004.)

"This risk of death persisted after correction for other risk factors, suggesting that hypoglycemia may independently contribute to this increased risk," Dr. Bellomo said.

Increasing severity of hypoglycemia was associated with significantly increased mortality rate (P < .001). After adjustment for insulin treatment, hypoglycemia was independently associated with an increased risk for death, cardiovascular death, and death from infectious disease.

"Our results suggest that any tolerance of mild to moderate hypoglycemia by intensive care clinicians may be undesirable," Dr. Bellomo said. "In this regard, newer technologies such as continuous glucose monitoring in the ICU setting might help avoid hypoglycemia or identify it earlier."

Limitations of this study include retrospective design, creating the potential for systematic error and bias; observational design, preventing determination of causality; and setting at only 2 centers, limiting generalizability.

"In critically ill patients, an association exists between even mild or moderate hypoglycemia and mortality," the study authors write. "Even after adjustment for insulin therapy or timing of hypoglycemic episode, the more severe the hypoglycemia, the greater the risk of death."

In an accompanying editorial, James S. Krinsley, MD, from Stamford Hospital in Stamford, Connecticut, and Mark T. Keegan, MD, from Mayo Clinic in Rochester, Minnesota, note that the development and clinical implementation of continuous or near-continuous glucose monitoring devices and "closed-loop" glycemic control systems may be helpful.

"With the use of these new technologies, coupled with algorithm-driven treatment protocols, the rate of hypoglycaemia should plummet; moreover, studies can be completed to prospectively evaluate the potential benefit in targeting a reduction in glycemic variability as an additional therapeutic goal," Drs. Krinsley and Keegan write. "Until then, we think that the study by Egi et al confirms the deleterious effect of hypoglycemia, especially severe hypoglycemia, in critically ill patients; highlights the complexity of this clinical problem; and reinforces the principle that clinicians practicing glycemic control must do so safely."

This study was supported by a grant from the Austin Hospital Intensive Care Trust Fund.

Mayo Clin Proc. 2010;85:215-216, 217-224.