Performance of Subcutaneous Continuous Glucose Monitoring in Adult Critically Ill Patients Receiving Vasopressor Therapy.

Background: Subcutaneous continuous glucose monitoring (CGM) may facilitate glucose control in the ICU. We aimed to assess the accuracy of CGM (Dexcom G6) against arterial blood glucose (ABG) in adult critically ill patients receiving intravenous insulin infusion and vasopressor therapy. We also aimed to assess feasibility and tolerability of CGM in this setting. Methods: We included ICU patients receiving mechanical ventilation, insulin, and vasopressor therapy. Numerical accuracy was assessed by the mean absolute relative difference (MARD), overall, across arterial glucose strata, over different noradrenaline equivalent infusion rates, and over time since CGM start. MARD <14% was considered acceptable. Clinical accuracy was assessed using Clarke Error Grid (CEG) analysis. Feasibility outcome included number and duration of interrupted sensor readings due to signal loss. Tolerability outcome included skin reactions related to sensor insertion or sensor adhesives. Results: We obtained 2946 paired samples from 40 patients (18 with type 2 diabetes) receiving a median (IQR) maximum noradrenaline equivalent infusion rate of 0.18 (0.08-0.33) µg/kg/min during CGM. Overall, MARD was 12.7% (95% CI 10.7-15.3), and 99.8% of CGM readings were within CEG zones A and B. MARD values ≥14% were observed when ABG was outside target range (6-10 mmol/L [108-180 mg/dL]) and with noradrenaline equivalent infusion rates above 0.10 µg/kg/min. Accuracy improved with time after CGM start, reaching MARD values <14% after 36 h. We observed four episodes of interrupted sensor readings due to signal loss, ranging from 5 to 20 min. We observed no skin reaction related to sensor insertion or sensor adhesives. Conclusions: In our ICU cohort of patients receiving vasopressor infusion, subcutaneous CGM demonstrated acceptable overall numerical and clinical accuracy. However, suboptimal accuracy may occur outside glucose ranges of 6-10 mmol/L (108-180 mg/dL), during higher dose vasopressor infusion, and during the first 36 h after CGM start.

Prevalence and impact of chronic dysglycaemia among patients with COVID-19 in Swedish intensive care units: a multicentre, retrospective cohort study.

OBJECTIVE: Using glycated haemoglobin A1c (HbA1c) screening, we aimed to determine the prevalence of chronic dysglycaemia among patients with COVID-19 admitted to the intensive care unit (ICU). Additionally, we aimed to explore the association between chronic dysglycaemia and clinical outcomes related to ICU stay. DESIGN: Multicentre retrospective observational study. SETTING: ICUs in three hospitals in Stockholm, Sweden. PARTICIPANTS: COVID-19 patients admitted to the ICU between 5 March 2020 and 13 August 2020 with available HbA1c at admission. Chronic dysglycaemia was determined based on previous diabetes history and HbA1c. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was the actual prevalence of chronic dysglycaemia (pre-diabetes, unknown diabetes or known diabetes) among COVID-19 patients. Secondary outcome was the association of chronic dysglycaemia with 90-day mortality, ICU length of stay, duration of invasive mechanical ventilation (IMV) and renal replacement therapy (RRT), accounting for treatment selection bias. RESULTS: A total of 308 patients with available admission HbA1c were included. Chronic dysglycaemia prevalence assessment was restricted to 206 patients admitted ICUs in which HbA1c was measured on all admitted patients. Chronic dysglycaemia was present in 82.0% (95% CI 76.1% to 87.0%) of patients, with pre-diabetes present in 40.2% (95% CI 33.5% to 47.3%), unknown diabetes in 20.9% (95% CI 15.5% to 27.1%), well-controlled diabetes in 7.8% (95% CI 4.5% to 12.3%) and uncontrolled diabetes in 13.1% (95% CI 8.8% to 18.5%). All patients with available HbA1c were included for the analysis of the relationship between chronic dysglycaemia and secondary outcomes. We found no independent association between chronic dysglycaemia and 90-day mortality, ICU length of stay or duration of IMV. After excluding patients with specific treatment limitations, no association between chronic dysglycaemia and RRT use was observed. CONCLUSIONS: In our cohort of critically ill COVID-19 patients, the prevalence of chronic dysglycaemia was 82%. We found no robust associations between chronic dysglycaemia and clinical outcomes when accounting for treatment limitations.

Glycaemic control and sepsis risk in adults with type 1 diabetes.

AIMS: To study the association between glycated haemoglobin (HbA1c) and sepsis in adults with type 1 diabetes, and to explore the relationship between HbA1c and mortality among individuals who developed sepsis. MATERIALS AND METHODS: We included 33 549 adult individuals with type 1 diabetes recorded in the Swedish National Diabetes Register between January 2005 and December 2015. We used multivariable Cox regression and restricted cubic spline analyses to study the relationship between HbA1c values and sepsis occurrence and association between HbA1c and mortality among those with sepsis. RESULTS: In total, 713 (2.1%) individuals developed sepsis during the study period. Compared with the HbA1c reference interval of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was: 2.50 [95% confidence interval (CI) 1.18-5.29] for HbA1c <43 mmol/mol; 1.88 (95% CI 0.96-3.67) for HbA1c 43-47 mmol/mol; 1.78 (95% CI 1.09-2.89) for HbA1c 53-62 mmol/mol; 1.86 (95% CI 1.14-3.03) for HbA1c 63-72 mmol/mol; 3.15 (95% CI 1.91-5.19) for HbA1c 73-82 mmol/mol; and 4.26 (95% CI 2.53-7.16) for HbA1c >82 mmol/mol. On multivariable restricted cubic spline analysis, we found a J-shaped association between HbA1c and sepsis risk, with the lowest risk observed at HbA1c of approximately 53 mmol/mol. We found no association between HbA1c and mortality among those individuals who developed sepsis. CONCLUSIONS: In our nationwide observational study of adult individuals with type 1 diabetes we found a J-shaped relationship between HbA1c and risk of sepsis, with the lowest risk at HbA1c levels about 53 mmol/mol (7.0%). HbA1c was not associated with mortality in individuals affected by sepsis.

Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes.

OBJECTIVE: To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes, and to assess the association between sepsis and all-cause mortality in such patients. RESEARCH DESIGN AND METHODS: We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between 1 January 2005 and 31 December 2015. The association between sepsis and death was examined using multivariable Cox regression analysis. RESULTS: Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07-1.24) for HbA1c <43 mmol/mol (6.1%), 0.93 (0.87-0.99) for HbA1c 53-62 mmol/mol (7.0-7.8%), 1.05 (0.97-1.13) for HbA1c 63-72 mmol/mol (7.9-8.7%), 1.14 (1.04-1.25) for HbA1c 73-82 mmol/mol (8.8-9.7%), and 1.52 (1.37-1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73-0.82) per SD; it increased thereafter (P for nonlinearity <0.001). As compared with patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03-4.30). CONCLUSIONS: In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a fourfold increased risk of death among those developing sepsis.

Glycemic lability index and mortality in critically ill patients-A multicenter cohort study.

BACKGROUND: Emerging evidence indicates a relationship between glycemic variability during intensive care unit (ICU) admission and death. We assessed whether mean glucose, hypoglycemia occurrence, or premorbid glycemic control modified this relationship. METHODS: In this retrospective, multicenter cohort study, we included adult patients admitted to five ICUs in Australia and Sweden with available preadmission glycated hemoglobin A1c (HbA1c) and three or more glucose readings. We calculated the glycemic lability index (GLI), a measure of glycemic variability, and the time-weighted average blood glucose (TWA-BG) from all glucose readings. We used logistic regression analysis with adjustment for hypoglycemia and admission characteristics to assess the independent association of GLI (above vs. below cohort median) and TWA-BG (above vs. below cohort median) with hospital mortality. RESULTS: Among 2305 patients, 859 (37%) had diabetes, median GLI was 40 [mmol/L]2 /h/week, median TWA-BG was 8.2 mmol/L, 171 (7%) developed hypoglycemia, and 371 (16%) died. The adjusted odds ratio for death was 1.61 (95% CI, 1.19-2.15; P = .002) for GLI above versus below median and 1.06 (95% CI, 0.80-1.41; P = .67) for TWA-BG above versus below median. The relationship between GLI and mortality was not modified by TWA-BG (P [interaction] = 0.66), a history of diabetes (P [interaction] = 0.89) or by HbA1c ≥52 mmol/mol (vs. <52 mmol/mol) (P [interaction] = 0.29). CONCLUSION: In adult patients admitted to an ICU in Sweden and Australia, a high GLI was associated with increased hospital mortality irrespective of the level of mean glycemia, hypoglycemia occurrence, or premorbid glycemic control. These findings support the assessment of interventions to reduce glycemic variability during critical illness.

Prevalence and impact of chronic dysglycemia in intensive care unit patients-A retrospective cohort study.

BACKGROUND: The prevalence of chronic dysglycemia (diabetes and prediabetes) in patients admitted to Swedish intensive care units (ICUs) is unknown. We aimed to determine the prevalence of such chronic dysglycemia and asses its impact on blood glucose control and patient-centered outcomes in critically ill patients. METHODS: In this retrospective observational cohort study, we obtained glycated hemoglobin A1c (HbA1c) in patients admitted to four tertiary ICUs in Sweden between March and August 2016. Based on previous diabetes history and HbA1c we determined the prevalence of chronic dysglycemia. We used multivariable regression analyses to study the association of chronic dysglycemia with the time-weighted average blood glucose concentration, glycemic lability index (GLI), and development of hypoglycemia (co-primary outcomes), and with ICU length of stay, mechanical ventilation duration, renal replacement therapy (RRT) use, vasopressor use, ICU-acquired infections, and mortality (exploratory clinical outcomes). RESULTS: Of 943 patients, 312 (33%) had chronic dysglycemia. Of these 312 patients, 84 (27%) had prediabetes, 43 (14%) had undiagnosed diabetes and 185 (59%) had known diabetes. Chronic dysglycemia was independently associated with higher time-weighted average blood glucose concentration (P < .001), higher GLI (P < .001), and hypoglycemia (P < .001). Chronic dysglycemia was independently associated with RRT use (adjusted odds ratio 1.97, 95% CI 1.24-3.13, P = .004) but not with other exploratory clinical outcomes. CONCLUSIONS: In four tertiary Swedish ICUs, measurement of HbA1c showed that one-third of patients had chronic dysglycemia. Chronic dysglycemia was associated with marked derangements in glycemic control, and a greater need for renal replacement therapy.

Hemoglobin A1c and Permissive Hyperglycemia in Patients in the Intensive Care Unit with Diabetes.

Glycated hemoglobin A1c can be used to assess intensive care unit patients' level of chronic glycemic control. Compared with patients with normal glycated hemoglobin A1c, patients with elevated glycated hemoglobin A1c seem to better tolerate hyperglycemia and large glucose fluctuations during critical illness. The risks associated with hypoglycemia are markedly greater among patients with elevated glycated hemoglobin A1c. Observational studies suggest that more liberal targets further decrease the occurrence of hypoglycemia in patients with diabetes with elevated glycated hemoglobin A1c. Whether glycated hemoglobin A1c should be used to individualize glucose control during critical illness should be assessed in randomized trials.