LABORATORIO DE URGENCIAS

Society of Critical Care Medicine Guidelines on Glycemic Control for Critically Ill Children and Adults 2024: Executive Summary

Participants from the following institutions:
1 Division of Critical Care, Department of Medicine, Mackenzie Health, Vaughan, ON, Canada. 2 GUIDE Canada, McMaster University, Hamilton, ON, Canada
3 System Critical Care Pharmacy Services Leader, Houston Methodist Hospital, Houston, TX.
4 Adult and Pediatric Critical Care Specialist, University of Utah School of Medicine, Salt Lake City, UT.
5 Department of Nurse Anesthesia, School of Nursing, University of Pittsburgh, Pittsburgh, PA. 6 Harvard Medical School and Division Chief, Medical Critical Care, Boston Children’s Hospital, Boston, MA.
7 Emory Critical Care Center, Atlanta, GA
8 Salt Lake City, UT.
9 Pediatric Critical Care Pharmacist, New Hanover Regional Medical Center, Wilmington, NC. 10 Pulmonary Critical Care and Sleep Medicine at the University of Tennessee Health Science Center, Memphis, TN.
11 Kaysville, UT.
12 Department of Nursing and Clinical Care Services—Critical Care, University of Pennsylvania School of Nursing, Children’s Hospital of Philadelphia, Philadelphia, PA.
13 Director of Critical Care, Emeritus, Vagelos Columbia University College of Physicians and Surgeons, Stamford Hospital, Stamford, CT.
14 Division of Critical Care, Intermountain Medical Center, Salt Lake City, UT.
15 Department of Anesthesiology, Division of Critical Care, University of Wisconsin School of Medicine & Public Health, Madison, WI.
16 Division of Cardiac Surgery, Critical Care Western, London Health Sciences Centre, London, ON, Canada.
17 Medical Director for Research and Teaching, Erasme Hospital, Hôpital Universitaire de Bruxelles, Brussels, Belgium.
18 Departments of Anesthesiology, Critical Care and Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
19 Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA.
20 School of Medicine, Emory University, Atlanta, GA.
21 Lebanon, IN

                                                                                                                                              Critical Care Medicine - 2024

Hyperglycemia is common in critically ill patients, is a marker for se[1]verity of illness, and may contribute directly to morbidity or mortality. Intensive insulin therapy (INT) had been shown to influence mor[1]tality and morbidity outcomes in specific research settings with early dextrose/ nutritional support, but benefits are difficult to achieve in most clinical set[1]tings without significant risk of hypoglycemia and associated complications.
Current consensus guidelines suggest targeting a moderate or conventional glucose control (CONV) level of glycemia to avoid extremes and minimize gly[1]cemic variability, excessive workload, and ensure consistent utilization (1, 2). This guideline addresses the clinical equipoise regarding target glucose levels for critically ill adult and pediatric (defined as ≥ 42wk adjusted gestational age) patients, along with monitoring frequency and methods (3). Neonatal patients were excluded due to their fundamental differences in physiology, nutrition, and inadequate expertise within the guideline taskforce.
This executive sum[1]mary describes key points from the full guideline document. Further, this guideline is an update of the 2012 guidelines for insulin infusion therapy (4). We convened a taskforce consisting of 22 members: 19 experts in adult and pediatric critical care, endocrinology, pharmacy, advanced practice providers, one methodologist from the Guidelines in Intensive Care Development and Evaluation group, and two patient/family members. The panel generated a series of clinical questions, identified and rated outcomes based on perceived im[1]portance to patients, performed systematic reviews of literature from January 2000 to January 2023, and generated a series of statements using The Grading of Recommendations, Assessment, Development, and Evaluation method[1]ology. The parameters that define our comparison groups were discussed extensively, as the published range for INT insulin targets varies from 4.4 to as much as 8.3 mmol/L (80–150mg/dL) and CONV varies from 7.8 to 12 mmol/L (140–215mg/dL).
The ranges reported were inclusive of a majority of appli[1]cable literature. Studies that did not compare these target ranges in critically ill patients were excluded.
Where evidence was inadequate, we made “in our practice” statements reflecting panel practices or “good practice” statements, which are considered equivalent to a strong recommendation. Recommendations are generally pre[1]sented for adult or pediatric populations, but some were applicable to both. Subpopulations (e.g., medical, surgical, neurologic, trauma, etc.) were evalu[1]ated and analyzed when data were available.
This executive summary provides an overview of several key recommendations, but the full document should be read for the complete recommendations and detailed evidence and justification (3). Key guideline statements for both adults and children are summa[1]rized in Table 1 and compared with a previous related guideline on the use of an insulin infusion for management of hyperglycemia in critically ill patients

 KEY RECOMMENDATIONS

# Adult Target
Question: Should insulin infusion therapy be titrated to achieve INT glucose levels, 4.4–7.7 mmol/L (80– 139mg/dL) or CONV glucose levels, 7.8–11.1 mmol/L (140–200mg/dL) for unselected (mixed) critically ill adults or any patient subgroups? Good Practice Statement: Clinicians should use glycemic management protocols and procedures that demonstrate a low risk of hypoglycemia among critically ill adults and should treat hypoglycemia without delay.
Recommendation: Based on available randomized controlled trial (RCT) data, in critically ill adults, we suggest against titrating an insulin infusion to a lower blood glucose (BG) target INT, 4.4–7.7 mmol/L (80–139mg/dL) as compared with a higher BG target range, CONV 7.8–11.1 mmol/L (140–200mg/ dL) to reduce the risk of hypoglycemia (Conditional recommendation; moderate certainty of evidence).
Research Statement: Observational data suggest a potential benefit of personalized glucose targets that more closely match chronic prehospital glycemic control. We recommend high-quality interventional trials of individualized glycemic targets in critically ill adults, stratified by prior glycemic control (such as indicated by glycosylated hemoglobin).
Rationale. Clinical benefits of INT have not been consistently demonstrated in the RCTs included in our meta-analysis; specifically no effect is shown on mortality among mixed populations of ICU patients.
However, INT targets were associated with increased frequency of severe hypoglycemia, less than 2.2 mmol/L (40mg/dL) compared with CONV targets, al[1]though there was a reduced infection risk, and lower ICU length of stay (LOS) with INT vs. CONV targets (5–42). In neurologic and cardiac surgery subsets, INT targets were associated with increased risk of severe hypoglycemia and although the cardiac surgery subset had a lower ICU mortality and lower critical illness polyneuropathy (both from a single clinical trial) there were no other outcome benefits (hospital mortality, any infection) (5, 25–31, 40–44). A large RCT of insulin infusion targeting tight glu[1]cose control without early parenteral nutrition (TGC[1]Fast) comparing insulin titrated to INT vs. a higher target than the CONV range in this guideline, 10–11.9 mmol/L (180–215mg/dL) was published after our lit[1]erature review but similarly found no difference in outcomes (time to discharge alive from ICU or 90-d mortality) despite low rates of hypoglycemia in both groups (45).
As a result, the upper limit for a glycemic target with insulin infusion is not well defined with current literature. Further, it appears that lower targets may be acceptable for selected patients if the risk of hy[1]poglycemia is documented to be negligible when using a safe and effective protocol. Although observational data suggest a potential role for personalized glucose targets relative to a history of DM, the TGC-Fast trial showed no benefit of INT targets despite 80% of the patients having no history of DM (45–53).
The panel recommends prospective randomized clinical trials using individualized targets for insulin titration, which will inform the need to revise this recommendation in the future.

# Pediatric Target
Question: Should insulin therapy be titrated to achieve INT glucose levels, 4.4–7.7 mmol/L (80– 139 mg/dL) or CONV glucose levels, 7.8–11.1 mmol/L (140–200 mg/dL) for unselected (mixed) critically ill children?
Good Practice Statement: Clinicians should use glycemic management protocols and procedures that demonstrate a low risk of hypoglycemia among critically ill children and should treat hypoglycemia without delay.
Recommendation: We recommend against INT BG control, 4.4–7.7 mmol/L (80–139mg/dL) as compared with CONV BG control, 7.8–11.1 mmol/L (140–200mg/dL) in critically ill children (defined by the pediatric panel as ≥ 42wk adjusted gestational age) (strong recommendation, moderate certainty evidence).
Rationale. INT targets were associated with increased frequency of severe hypoglycemia (< 2.2 mmol/L [40mg/dL]), shorter ICU LOS, but no effect on mor[1]tality or neurocognitive outcomes among mixed ICU and postcardiac surgery patients (54–62). The high risk of severe hypoglycemia outweighs the trivial clin[1]ical benefits of INT glucose control among critically ill children. The impact of hypoglycemia on cognitive development is a special consideration in children. While RCT data were prioritized for this guideline, observational data suggest poorer cognitive perfor[1]mance among children with moderate or severe hy[1]poglycemia events, lending additional importance to hypoglycemia avoidance (54, 57, 63, 64).
Like the adult population, the panel recommends prospective randomized clinical trials using individualized targets based on preexisting glycemic control to inform future practice changes

# Critically ill adults and children
Question: In critically ill adults and children on insulin infusion therapy, should a protocol that includes explicit decision support tools be used compared with conventional protocols for the management of hyperglycemia?
Recommendations. We suggest use of a protocol that includes explicit decision support tools (tools) over a protocol with no such tools in critically ill adults re[1]ceiving IV insulin infusions for the management of hy[1]perglycemia (conditional recommendation, moderate certainty evidence). We suggest use of explicit decision support tools over no such tools in critically ill pediatric patients re[1]ceiving IV insulin infusions for the management of hy[1]perglycemia (conditional recommendation; very low certainty evidence).
Rationale. We defined those elements of explicit clinical decision support tools that were critical com[1]ponents of acceptable protocols, preferably with com[1]puterized support and interoperability of the tool with the electronic health record. While patient outcomes were prioritized for this guideline, the panel acknowl[1]edges that insulin titration protocols add to bedside caregiver cognitive burden and workload and could be minimized with a well-designed explicit decision support tool that directs treatment (65, 66). Protocols incorporating these tools were associated with reduced frequency of moderate hypoglycemia less than 3.3 mmol/L (60mg/dL) and greater proportion of BG values within the target range (45, 50, 67–76). There were no effects on other critical outcomes such as hospital mortality or ICU LOS (moderate certainty), ICU mortality or quality of life at 90 days (low cer[1]tainty). The TGC-Fast trial of INT vs. a glucose target of 10–11.9 mmol/L (180–215mg/dL) used a computer algorithm integrated into the electronic health record with alerts to guide insulin dosing and monitoring intervals of 1–4 hours (45). With these components, a low rate of hypoglycemia was reported in this mul[1]ticenter trial of adults in both INT and higher target groups. While most other studies evaluated adult pro[1]tocols it was determined that the processes of glycemic management are comparable between adults and chil[1]dren, leading to comparable statements and endorse[1]ment of the need for high-quality interventional trials in both age groups.

CONCLUSIONS

Guidelines are limited by the quality of published data in RCTs and additional research on various aspects of glycemic control is needed. Key guideline statements are summarized in this executive summary but there is sig[1]nificant additional detail in the full document regarding hyperglycemic triggers, route of insulin administra[1]tion, frequency of glucose monitoring, and monitoring devices (3). Clinicians should also examine the com[1]plete explanation of rationale and evidence to recom[1]mendation discussions to gain insight into strengths and weaknesses of existing data when considering how to incorporate guidelines into clinical practice.

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