Palash Kar

Management of critically ill patients with type 2 diabetes: The need for personalised therapy

Critical illness in patients with pre-existing diabetes frequently causes deterioration in glycaemic control. Despite the prevalence of diabetes in patients admitted to hospital and intensive care units, the ideal management of hyperglycaemia in these groups is uncertain. There are data that suggest that acute hyperglycaemia in critically ill patients without diabetes is associated with increased mortality and morbidity. Exogenous insulin to keep blood glucose concentrations < 10 mmol/L is accepted as standard of care in this group. However, preliminary data have recently been reported that suggest that chronic hyperglycaemia may result in conditioning, which protects these patients against damage mediated by acute hyperglycaemia. Furthermore, acute glucose-lowering to < 10 mmol/L in patients with diabetes with inadequate glycaemic control prior to their critical illness appears to have the capacity to cause harm. This review focuses on glycaemic control in critically ill patients with type 2 diabetes, the potential for harm from glucose-lowering and the rationale for personalised therapy.

Liberal Glycemic Control in Critically Ill Patients With Type 2 Diabetes: An Exploratory Study.

Objectives: The optimal blood glucose target in critically ill patients with preexisting diabetes and chronic hyperglycemia is unknown. In such patients, we aimed to determine whether a “ liberal” approach to glycemic control would reduce hypoglycemia and glycemic variability and appear safe. Design: Prospective, open-label, sequential-period exploratory study. Setting: Medical-surgical ICU. Patients: During sequential 6-month periods, we studied 83 patients with preexisting type 2 diabetes and chronic hyperglycemia (glycated hemoglobin, ≥ 7.0% at ICU admission). Intervention: During the “standard care” period, 52 patients received insulin to treat blood glucose concentrations greater than 10 mmol/L whereas during the “liberal” period, 31 patients received insulin to treat blood glucose concentrations greater than 14 mmol/L. Measurements and Main Results: Time-weighted mean glucose concentrations and the number and duration of moderate (< 4.0 mmol/L) and severe (⩽ 2.2 mmol/L) hypoglycemic episodes were recorded, with moderate and severe hypoglycemic episodes grouped together. Glycemic variability was assessed by calculating the coefficient of variability for each patient. Safety was evaluated using clinical outcomes and plasma concentrations of markers of inflammation, glucose-turnover, and oxidative stress. Mean glucose (TWglucoseday 0–7, standard care: 9.3 [1.8] vs liberal: 10.3 [2.1] mmol/L; p = 0.02) and nadir blood glucose (4.4 [1.5] vs 5.5 [1.6] mmol/L; p < 0.01) were increased during the liberal period. There was a signal toward reduced risk of moderate-severe hypoglycemia (relative risk: liberal compared with standard care: 0.47 [95% CI, 0.19–1.13]; p = 0.09). Ten patients (19%) during the standard period and one patient (3%) during the liberal period had recurrent episodes of moderate-severe hypoglycemia. Liberal therapy reduced glycemic variability (coefficient of variability, 33.2% [12.9%] vs 23.8% [7.7%]; p < 0.01). Biomarker data and clinical outcomes were similar. Conclusions: In critically ill patients with type 2 diabetes and chronic hyperglycaemia, liberal glycemic control appears to attenuate glycemic variability and may reduce the prevalence of moderate-severe hypoglycemia.

Critical Illness Is Associated With Impaired Gallbladder Emptying as Assessed by 3d Ultrasound

Objective: To quantify gallbladder dysfunction during critical illness. Design: Prospective observational comparison study of nutrient-stimulated gallbladder emptying in health and critical illness. Setting: Single-centre mixed medical/surgical ICU. Patients: Twenty-four mechanically ventilated critically ill patients suitable to receive enteral nutrition were compared with 12 healthy subjects. Interventions: Participants were studied after an 8-hour fast. Between 0 and 120 minutes, high-fat nutrient (20% intralipid) was infused via a postpyloric catheter into the duodenum at 2 kcal/min. Measurements and Main Results: Three-dimensional images of the gallbladder were acquired at 30-minute intervals from –30 to 180 minutes. Ejection fraction (%) was calculated as changes between 0 and 120 minutes. Blood samples were obtained at 30-minute intervals for plasma cholecystokinin. Data are mean (SD) or median [interquartile range]. In the critically ill, fasting gallbladder volumes (critically ill, 61 mL [36–100 mL] vs healthy, 22 mL [15–25] mL; p < 0.001] and wall thickness (0.45 mm [0.15 mm] vs 0.26 mm [0.08 mm]; p < 0.001] were substantially greater, and sludge was evident in the majority of patients (71% vs 0%). Nutrient-stimulated emptying was incomplete in the critically ill after 120 minutes but was essentially complete in the healthy individuals (22 mL [9–66 mL] vs 4 mL [3–5 mL]; p < 0.01]. In five critically ill patients (21%), there was no change in gallbladder volume in response to nutrient, and overall ejection fraction was reduced in the critically ill (50% [8–83%] vs 77 [72–84%]; p = 0.01]. There were no differences in fasting or incremental cholecystokinin concentrations. Conclusions: Fasted critically ill patients have larger, thicker-walled gallbladders than healthy subjects and nutrient-stimulated gallbladder emptying is impaired with “gallbladder paresis” occurring in approximately 20%.

Glycated Hemoglobin A1c Levels Are Not Affected by Critical Illness

Objectives: Glycated hemoglobin A1c is used to estimate glycemic control. However, its value upon ICU admission may be altered by critical illness and not reflect true glycemic status. We assessed the relationship between ICU admission glycated hemoglobin A1c and premorbid glycated hemoglobin A1c levels. Design: Retrospective observational cohort study. Setting: Two tertiary ICUs in Australia. Patients: Cohort of 69 critically ill patients with diabetes and glycated hemoglobin A1c levels measured upon ICU admission and during the month prior to admission. Interventions: Measurement of glycated hemoglobin A1c. Measurements and Main Results: Mean (SD) glycated hemoglobin A1c level was 7.5% (1.8%) upon ICU admission and 7.8% (2.0%) in previous measurements from the preceding 30 days. The change in glycated hemoglobin A1c did not correlate with time elapsed between the two measurements (r 2 = 0.00005; p = 0.95), but there was a strong correlation between admission glycated hemoglobin A1c levels and premorbid glycated hemoglobin A1c levels (r 2 = 0.89; p < 0.001). Conclusions: Glycated hemoglobin A1c levels are not altered by the onset of critical illness. Glycated hemoglobin A1c quantified at ICU admission can, therefore, be used to reliably estimate chronic glycemic control and guide acute glycemic therapy.

Glycated haemoglobin is increased in critically ill patients with stress hyperglycaemia: Implications for risk of diabetes in survivors of critical illness

It remains uncertain if stress hyperglycaemia (SH) indicates a long-term predisposition to the development of type 2 diabetes. We conducted a retrospective observational study in critically ill patients and found SH to be associated with an increased HbA1c, which may indicate an increased risk of type 2 diabetes.

Antecedent hypoglycemia does not attenuate the acceleration of gastric emptying by hypoglycemia.

Context: Acute hypoglycemia accelerates gastric emptying and increases cardiac contractility. However, antecedent hypoglycemia attenuates counterregulatory hormonal responses to subsequent hypoglycemia. Objective: To determine the effect of antecedent hypoglycemia on gastric and cardiac responses to subsequent hypoglycemia in health. Design: A prospective, single‐blind, randomized, crossover study (performed at the Royal Adelaide Hospital, Adelaide, South Australia, Australia). Patients: Ten healthy young men 18 to 35 years of age were studied for 36 hours on two occasions. Interventions: Participants were randomly assigned to either antecedent hypoglycemia [three 45‐minute periods of strict hypoglycemia (2.8 mmol/L] or control [three 45‐minute periods of strict euglycemia (6 mmol/L)] during the initial 12‐hour period. Participants were monitored overnight, and the following morning blood glucose was clamped at 2.8 mmol/L for 60 minutes and then at 6 mmol/L for 120 minutes. At least 6 weeks later participants returned for the alternative intervention. Gastric emptying and cardiac fractional shortening were measured with scintigraphy and two‐dimensional echocardiography, respectively, on the morning of all 4 study days. Results: A single, acute episode of hypoglycemia accelerated gastric emptying (P = 0.01) and augmented fractional shortening (P < 0.01). Gastric emptying was unaffected by antecedent hypoglycemia (P = 0.74) whereas fractional shortening showed a trend to attenuation (P = 0.06). The adrenaline response was diminished (P < 0.05) by antecedent hypoglycemia Conclusions: In health, the acceleration of gastric emptying during hypoglycemia is unaffected by antecedent hypoglycemia, whereas the increase in cardiac contractility may be attenuated.

Stress induced hyperglycemia and the subsequent risk of type 2 diabetes in survivors of critical illness

Objective Stress induced hyperglycemia occurs in critically ill patients who have normal glucose tolerance following resolution of their acute illness. The objective was to evaluate the association between stress induced hyperglycemia and incident diabetes in survivors of critical illness. Design Retrospective cohort study. Setting All adult patients surviving admission to a public hospital intensive care unit (ICU) in South Australia between 2004 and 2011. Patients Stress induced hyperglycemia was defined as a blood glucose ≥ 11.1 mmol/L (200 mg/dL) within 24 hours of ICU admission. Prevalent diabetes was identified through ICD-10 coding or prior registration with the Australian National Diabetes Service Scheme (NDSS). Incident diabetes was identified as NDSS registration beyond 30 days after hospital discharge until July 2015. The predicted risk of developing diabetes was described as sub-hazard ratios using competing risk regression. Survival was assessed using Cox proportional hazards regression. Main Results Stress induced hyperglycemia was identified in 2,883 (17%) of 17,074 patients without diabetes. The incidence of type 2 diabetes following critical illness was 4.8% (821 of 17,074). The risk of diabetes in patients with stress induced hyperglycemia was approximately double that of those without (HR 1.91 (95% CI 1.62, 2.26), p<0.001) and was sustained regardless of age or severity of illness. Conclusions Stress induced hyperglycemia identifies patients at subsequent risk of incident diabetes.

Postprandial hypotension in older survivors of critical illness

Purpose: In older people postprandial hypotension occurs frequently; and is an independent risk factor for falls, cardiovascular events, stroke and death. The primary aim of this pilot study was to estimate the frequency of postprandial hypotension and evaluate the mechanisms underlying this condition in older survivors of an Intensive Care Unit (ICU). Materials and methods: Thirty‐five older (>65years) survivors were studied 3months after discharge. After an overnight fast, participants consumed a 300mL drink containing 75g glucose, labelled with 20MBq 99mTc‐calcium phytate. Patients had concurrent measurements of blood pressure, heart rate, blood glucose and gastric emptying following drink ingestion. Proportion of participants is presented as percent (95% CI) and continuous variables as mean (SD). Results: Postprandial hypotension was evident in 10 (29%; 95% CI 14–44), orthostatic hypotension in 2 (6%; 95% CI 0–13) and cardiovascular autonomic dysfunction in 2 (6%; 95% CI 0–13) participants. The maximal postprandial nadir for systolic blood pressure and diastolic blood pressures were −29 (14) mmHg and −18 (7) mmHg. Conclusions: In this cohort of older survivors of ICU postprandial hypotension occurred frequently. This suggests that postprandial hypotension is an unrecognised issue in older ICU survivors. HIGHLIGHTSPostprandial hypotension is prevalent in older survivors of critical illness.Postprandial hypotension occurred more frequently than orthostatic hypotension.Symptoms of postprandial hypotension were rarely reported by patients.Postprandial hypotension may be an unrecognised problem in older ICU survivors.

Personalised glucose therapy: glucose targets in critically ill patients with pre-existing poorly controlled type 2 diabetes

In patients without pre-existing diabetes, hyperglycaemia during critical illness is associated with adverse outcomes. However, recent observational data suggest that in patients with pre-existing poorly controlled type 2 diabetes (defined as an HbA1c ≥7%) prior to their acute illness, targeting glucose concentrations < 10mmol/l is associated with harm [1]. Accordingly a higher glucose target may benefit these patients.

Nutrient-stimulated gallbladder emptying is incomplete during critical illness as assessed by 3D ultrasound

Gallbladder dysmotility has been implicated as a putative mechanism underlying acute acalculous cholecystitis and lipid malabsorption in the critically ill, despite nutrient-stimulated gallbladder emptying never having been quantified in this population. In health, endogenous cholecystokinin (CCK) stimulates gallbladder emptying.