Glycemic targets in critically ill adults: A mini-review

Table 1 Types of glycemic targets in intensive care unit

Glycemic target	Unit	Definition
Glucose	mmol/L	Concentration of glucose in blood or plasma. To convert to mg/dL, multiply by 18, i.e., 1 mmol/L = 18 mg/dL
COV	%	Coefficient of variation, a measure of glucose variability. COV = standard deviation divided by mean glucose × 100%
GG	mmol/L	Glycemic gap. GG = blood glucose - [(1.59 × HbA1c) - 2.59], HbA1c being used to estimate average glucose concentration over the prior 3 mo
Glucose variability	mmol/L	Maximum – minimum glucose in a given time period
SHR	Nil	Stress hyperglycemia ratio. SHR = plasma glucose divided by [(1.59 × HbA1c)–2.59], HbA1c being used to estimate average glucose concentration over the prior 3 mo

HbA1c: Glycosylated hemoglobin.

Table 2 Glycemic targets in intensive care unit by casemix and thresholds

Casemix	Blood sample	Method	Glycemic target	Evidence
Burns	Not stated	Not stated	Glucose > 7.8 mmol/L	Increased pneumonia, ventilator-associated pneumonia, and urinary tract infection; Obs[72]
Cardiac	Not stated	Not stated	Glucose 4.4-6.1 mmol/L	Decreased 30-d mortality compared to glucose 5-7.8 mmol/L; Obs[73]
DM	Not stated	Portable glucometer, blood gas analyzer	Glucose < 14 mmol/L	Decreased glycemic variability and incident hypoglycemia; before-and-after study[35]
DM	Arterial, venous	Blood gas analyzer	Glucose 10-14 mmol/L	Decreased incident hypoglycemia; before-and-after study[74]. No increased risk of hospital-acquired infectious, cardiovascular, renal or neurological complications; before-and-after study[75]
DM	Not stated	Portable glucometer	Glucose 5.6-7.8 mmol/L	Decreased complications (infection, cardiac events, respiratory failure, kidney failure) after coronary artery bypass graft surgery compared to glucose 7.8-10 mmol/L; RCT[34]
DM	Not stated	Portable glucometer	Glucose 5-7.8 mmol/L	Decreased 30-day mortality compared to glucose 4.4-6.1 mmol/L; Obs[76]
Medical	Capillary	Portable glucometer	Glucose > 7 mmol/L	Increased ICU mortality; Obs[77]
Medical-surgical	Arterial	Point-of-care or blood gas or laboratory analyzers	Glucose 8-10 mmol/L	Decreased 90-d mortality and incident severe hypoglycemia compared to glucose 4.5-6.0 mmol/L; RCT[31]
Medical-surgical	Not stated	Portable glucometer	Glucose 4.4-6.1 mmol/L	Decreased 30-d mortality compared to glucose 5-7.8 mmol/L in patients without DM; Obs[76]
Medical-surgical	Arterial	Point-of-care or blood gas or laboratory analyzers	Glucose 4.4-6.1 mmol/L	Increased incident severe hypoglycemia compared to more liberal control (95%CI of glucose -7.8-9.4) mmol/L; RCT[78]
Medical-surgical	Arterial, capillary	Glucometer	Glucose 10-11.1 mmol/L	Decreased incident severe hypoglycemia compared to glucose 4.4-6.1 mmol/L; RCT[46]
Medical-surgical	Arterial, capillary, venous	Glucometer or blood gas analyzer	Glucose 7.8-10 mmol/L	Decreased incident severe hypoglycemia compared to glucose 4.4-6.1 mmol/L; RCT[79]
Medical-surgical	Arterial	Portable glucometer	Glucose 7-9 mmol/L	Decreased ICU mortality compared to out-of-range glucose; Obs[80]
Medical-surgical	Arterial, capillary	Glucometer or blood gas analyzer	Glucose < 10 mmol/L	Decreased incident severe hypoglycemia compared to glucose 4.4-6.1 mmol/L; RCT[31,81]
Medical-surgical	Arterial	Glucometer	Glucose < 8 mmol/L	Decreased ICU mortality compared to higher glucose levels; Obs[82]
Medical-surgical	Arterial	Blood gas analyzer	Glucose > 8.3 mmol/L	Increased ICU mortality compared to glucose 6.1-8.3; Obs[83]
Medical-surgical	Arterial, capillary	Glucometer	Glucose < 8.2 mmol/L	Decreased ICU mortality compared to higher glucose levels; Obs[84]
Medical-surgical	Arterial, venous	Glucometer	Glucose 4.4-7.8 mmol/L	Decreased ICU and hospital mortality compared to glucose 7.8-10 mmol/L in patients without DM; Obs[26]
Medical-surgical	Not stated	Glucometer	Glucose 3.9-7.8 mmol/L	Time in range associated with decreased ICU mortality in patients without DM; Obs[85]; Time in range associated with decreased ICU mortality in patients receiving insulin; Obs[86]
Medical-surgical	Venous	Laboratory	Low SHR < 1	Decreased hospital mortality compared to SHR > 1 regardless of baseline HbA1c; Obs[87]
Post-CA	Capillary, venous	Not stated	Glucose 3.9-7.8 mmol/L	Higher survival, compared to higher glucose levels; Obs[88]
Post-CA	Not stated	Not stated	Glucose 4-10 mmol/L	Better neurological recovery, compared to higher glucose levels; Obs[33]
Surgical	Arterial	Blood gas analyzer	Glucose 4.4-6.1 mmol/L	Decreased hospital mortality, blood stream infections, acute renal failure, blood transfusion, critical-illness polyneuropathy, prolonged mechanical ventilation, compared to glucose 10-11.1 mmol/L; RCT[42]
Surgical	Not stated	Not stated	Glucose 4.4-6.1 mmol/L	Decreased post-operative renal failure and 30-d mortality compared to glucose > 8.3 mmol/L; Obs[89]
Surgical	Arterial, capillary, venous	Glucometer or blood gas analyzer	Glucose 4.4-7.8 mmol/L	Decreased hospital mortality compared to glucose >7.8 mmol/L; Obs[27]
Surgical	Not stated	Glucometer	Glucose 4-8 mmol/L	Decreased surgical site infection after coronary artery bypass graft surgery compared to glucose 4-10 mmol/L; before-and-after study[28]
Surgical	Arterial, venous	Continuous sensor, in a closed-loop system	Glucose 4.4-6.1 mmol/L	Decreased surgical site infection post- hepato-biliary-pancreatic surgery, compared to glucose 7.7-10.0 mmol/L; RCT[90]
Surgical	Arterial	Blood gas analyzer	Glucose 6.7-8.9 mmol/L	Decreased mortality compared to glucose 8.9-10 mmol/L; quasi-experimental (alternate allocation of participants)[91]
Surgical	Capillary	Glucometer	Glucose 6.1-8.3 mmol/L	Decreased surgical site infection and atrial fibrillation after coronary artery bypass graft surgery; before-and-after study[29]
TBI	Arterial	Blood gas analyzer	Glucose 3.5-6.5 mmol/L	Reduced intracranial hypertension and decreased rate of pneumonia, bacteremia and urinary tract infections during 2nd week, compared to glucose 5-8 mmol/L; Obs[5]
TBI	Not stated	Not stated	Glucose 4.4-6.7 mmol/L	Decreased risk of poor neurological outcomes but increased risk of hypoglycemia, and no mortality benefit, compared to higher glucose targets; systematic review of RCT[30]
TBI	Arterial	Point-of-care or blood gas or laboratory analyzers	Glucose 8-10 mmol/L	Decreased incident severe hypoglycemia, but no mortality benefit, compared to glucose 4.5-6.0 mmol/L; RCT[92]
TBI	Not stated	Not stated	Glucose < 11.1 mmol/L	Decreased hospital mortality compared to glucose > 11.1 mmol/L; Obs[93]
Trauma	Arterial, capillary, venous	Point-of-care or laboratory analyzers	Glucose < 7.8 mmol/L	Decreased ICU mortality compared to glucose > 7.8 mmol/L; Obs[94]
Trauma	Capillary	Not stated	Glucose < 10 mmol/L	Decreased hospital mortality compared to glucose > 10 mmol/L; Obs[32]

DM: Diabetes mellitus; HbA1c: Glycosylated hemoglobin; ICU: Intensive care unit; Obs: Observational study; RCT: Randomized controlled trial; SHR: Stress hyperglycemia ratio; TBI: Traumatic brain injury.

Table 3 Glycemic targets in intensive care unit by casemix and variability

Casemix	Blood sample	Method	Glycemic target	Evidence
Medical-surgical	Arterial, venous	Glucometer	Glucose variability (COV ≥ 20%)	Increased ICU and hospital mortality in patients without DM; Obs[26]
Medical-surgical	Arterial, capillary	Glucometer or blood gas analyzer	Glucose variability > 6 mmol/L	Increased ICU and hospital mortality; Obs[44]
Medical-surgical	Arterial	Glucometer or blood gas analyzer	Glucose variability > 4 mmol/L	Increased hospital mortality; Obs[10]
Post-CA	Arterial	Blood gas analyzer	Glucose variability < 5 mmol/L	Decreased hypoglycemia and mortality; Obs[45]
Post-CA	Not stated	Not stated	GG-min < 3.9 mmol/L	Better neurological recovery; Obs[95]

COV: Coefficient of variation; GG: Glycemic gap; GG-min: Minimum glycemic gap = minimum blood glucose - [(1.59 × HbA1c) - 2.59], HbA1c being used to estimate average glucose concentration over the prior 3 mo; ICU: Intensive care unit; Obs: Observational study.

Table 4 Choosing lower vs higher glycemic target ranges

Glycemic target range	Considerations favoring choice of glycemic target range
Lower glycemic target range (i.e., glucose 4.5-7.8 mmol/L)	(1) Patients without DM; (2) Patients with TBI; (3) Post-surgical patients at risk of surgical site infections; (4) Availability of intensive glucose monitoring and management; (5) Strict adherence to glycemic control protocols; and (6) Strict adherence to timely glucose measurements
Higher glycemic target range (i.e., glucose 7.8-10 mmol/L)	(1) Default choice for most patients; (2) Patients with DM; (3) Lack of intensive glucose monitoring and management; (4) Less than strict adherence to glycemic control protocols; and (5) Less than strict adherence to timely glucose measurements

DM: Diabetes mellitus; TBI: Traumatic brain injury.

Table 5 Selected guideline recommendations

Casemix	Guideline (Year)	Recommended glycemic target range
Medical-Surgical	American Diabetes Association: Diabetes Care in the Hospital (2021)[47]	7.8-10 mmol/L. Lower targets may be appropriate for selected patients if they can be achieved without significant hypoglycemia
Post-CA	European Resuscitation Council and European Society of Intensive Care Medicine guidelines (2021)[48]	7.8-10 mmol/L
Sepsis	Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock (2016)[49]	< 10 mmol/L and avoid hypoglycemia. Lower targets may be appropriate for selected patients if they can be achieved without significant hypoglycemia
Surgical	WHO recommendations on intraoperative and postoperative measures for surgical site infection prevention: an evidence-based global perspective (2016)[50]	Unable to define target range, though glucose control protocols recommended
TBI	Brain Trauma Foundation’s Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition (2016)[51]	No recommendation

CA: Cardiac arrest; TBI: Traumatic brain injury; WHO: World Health Organization.