The benefits of tight glycemic control in critical illness: Sweeter than assumed?

Abstract

Hyperglycemia has long been observed amongst critically ill patients and associated with increased mortality and morbidity. Tight glycemic control (TGC) is the clinical practice of controlling blood glucose (BG) down to the “normal” 4.4–6.1 mmol/L range of a healthy adult, aiming to avoid any potential deleterious effects of hyperglycemia. The ground-breaking Leuven trials reported a mortality benefit of approximately 10% when using this technique, which led many to endorse its benefits. In stark contrast, the multi-center normoglycemia in intensive care evaluation–survival using glucose algorithm regulation (NICE-SUGAR) trial, not only failed to replicate this outcome, but showed TGC appeared to be harmful. This review attempts to re-analyze the current literature and suggests that hope for a benefit from TGC should not be so hastily abandoned. Inconsistencies in study design make a like-for-like comparison of the Leuven and NICE-SUGAR trials challenging. Inadequate measures preventing hypoglycemic events are likely to have contributed to the increased mortality observed in the NICE-SUGAR treatment group. New technologies, including predictive models, are being developed to improve the safety of TGC, primarily by minimizing hypoglycemia. Intensive Care Units which are unequipped in trained staff and monitoring capacity would be unwise to attempt TGC, especially considering its yet undefined benefit and the deleterious nature of hypoglycemia. International recommendations now advise clinicians to ensure critically ill patients maintain a BG of <10 mmol/L. Despite encouraging evidence, currently we can only speculate and remain optimistic that the benefit of TGC in clinical practice is sweeter than assumed.

RSSDI-ESI clinical practice recommendations for the management of type 2 diabetes mellitus 2020

“…Intensive insulin therapy to maintain blood glucose at or below 110 mg/dL is known to reduce morbidity and mortality among critically ill patients in the surgical intensive care unit. [ 856 ] To maintain the patient in normoglycaemic range, the intensive insulin therapy was initiated when the blood glucose level reached renal threshold value usually ≥12 mmol/L in Leuven trial. Conversely in the NICE-SUGAR trial, intensive glucose control increased mortality among adults in the ICU: a blood glucose target of <180 mg/dL resulted in lower mortality than a target of 81 to 108 mg/dL [ Table 32 ].…”

“…Thus, change in hormonal regulation increases risk of hypoglycaemia if TGC protocols are not taken into consideration. [ 856 ]…”

Prednosti in slabosti različnih protokolov vodenja vrednosti glukoze v krvi pri kritično bolnih pacientih

“…Po drugi strani Krinsley (2015) na osnovi pregleda literature ugotavlja, da pri kritično bolnih pacientih ne moremo določiti optimalne vrednosti glukoze v krvi, saj predpisana koncentracija glukoze v krvi ne more biti ustrezna vsem kritično bolnim pacientom. Gardner (2014) navaja, da klinična praksa v protokolih vodenja vrednosti glukoze v krvi pri kritično bolnih pacientih za ciljne vrednosti postavlja območje 4,4−6,1 mmol/l z namenom izogniti se morebitnim škodljivim učinkom hiperglikemije.…”

Glycation abolishes the cardioprotective effects of albumin during ex vivo ischemia‐reperfusion

“…There is a growing interest to better understand the association between hyperglycemia and CVD, for example, acute myocardial infarction (AMI) (Soedamah‐Muthu et al. ; Gardner ; Martín‐timón et al. ).…”