Sodium glucose co-transporter-2 inhibitors in intensive care unit patients with type 2 diabetes: a pilot case control study.

BACKGROUND: Sodium glucose co-transporter-2 (SGLT2) inhibitors improve long-term cardiovascular and renal outcomes in individuals with type 2 diabetes. However, the safety of SGLT2 inhibitors in ICU patients with type 2 diabetes is uncertain. We aimed to perform a pilot study to assess the relationship between empagliflozin therapy and biochemical, and clinical outcomes in such patients. METHODS: We included 18 ICU patients with type 2 diabetes receiving empagliflozin (10 mg daily) and insulin to target glucose range of 10-14 mmol/l according to our liberal glucose control protocol for patients with diabetes (treatment group). Treatment group patients were matched on age, glycated hemoglobin A1c, and ICU duration with 72 ICU patients with type 2 diabetes exposed to the same target glucose range but who did not receive empagliflozin (control group). We compared changes in electrolyte and acid-base parameters, hypoglycemia, ketoacidosis, worsening kidney function, urine culture findings, and hospital mortality between the groups. RESULTS: Median (IQR) maximum increase in sodium and chloride levels were 3 (1-10) mmol/l and 3 (2-8) mmol/l in the control group and 9 (3-12) mmol/l and 8 (3-10) mmol/l in the treatment group (P = 0.045 for sodium, P = 0.059 for chloride). We observed no differences in strong ion difference, pH or base excess. Overall, 6% developed hypoglycemia in each group. No patient in the treatment group and one patient in the control group developed ketoacidosis. Worsening kidney function occurred in 18% and 29% of treatment and control group patients, respectively (P = 0.54). Urine cultures were positive in 22% of treatment group patients and 13% of control group patients (P = 0.28). Overall, 17% of treatment group patients and 19% of control group patients died in hospital (P = 0.79). CONCLUSIONS: In our pilot study of ICU patients with type 2 diabetes, empagliflozin therapy was associated with increases in sodium and chloride levels but was not significantly associated with acid-base changes, hypoglycemia, ketoacidosis, worsening kidney function, bacteriuria, or mortality.

Glycemic control and blood gas sampling frequency during continuous glucose monitoring in the intensive care unit: A before-and-after study.

BACKGROUND: Whether subcutaneous continuous glucose monitoring (CGM) can safely replace intermittent arterial blood gas glucose analyses in intensive care unit (ICU) patients remains uncertain. We aimed to compare CGM to blood gas glucose values and assess whether CGM use reduces blood gas sampling frequency and glucose variability in ICU patients with type 2 diabetes managed with liberal glucose control. METHODS: We used the FreeStyle Libre CGM in 15 ICU patients and compared their blood glucose metrics with a pre-CGM control population of 105 ICU patients with type 2 diabetes. Both groups received insulin to target glucose range of 10-14 mmol/L. We used linear regression analysis adjusted for illness severity to assess the association of CGM use with blood gas sampling frequency and glucose variability. We used mean absolute relative difference (MARD) and Clarke error grid analysis to assess accuracy of matched CGM-blood glucose values overall, across glucose stata (<10, 10-14, >14 mmol/L), and over time (≤48, 48-96, >96 h). RESULTS: We analyzed 483 matched glucose values. Overall MARD was 11.5 (95% CI, 10.7-12.3)% with 99% of readings in Clarke zones A and B. MARD was 15.5% for glucose values <10 mmol/L, 11.1% at 10-14 mmol/L, and 11.4% >14 mmol/L. MARD was 13.8% in the first 48 h, 10.9% at 48-96 h, and 8.9% beyond 96 h. CGM use was associated with 30% reduction in blood gas sampling frequency. CGM use was not associated with glucose variability as determined by glycemic lability index or standard deviation of blood glucose. CONCLUSIONS: In our cohort of ICU patients with type 2 diabetes receiving liberal glycemic control, CGM showed acceptable accuracy and was associated with a reduction in blood gas sampling frequency without compromising glucose control. Lowest accuracy was observed at glucose values below 10 mmol/L and during the first 48 h of CGM use.

Prolonged postoperative cerebral oxygen desaturation after cardiac surgery: A prospective observational study.

BACKGROUND: Near-infrared spectroscopy (NIRS) is used routinely to monitor cerebral tissue oxygen saturation (SctO2) during cardiopulmonary bypass (CPB) but is rarely employed outside the operating room. Previous studies indicate that patients are at risk of postoperative cerebral oxygen desaturation after cardiac surgery. OBJECTIVES: We aimed to assess perioperative and postoperative changes in NIRS-derived SctO2 in cardiac surgery patients. DESIGN: Prospective observational study. SETTING: The study was conducted in a tertiary referral university hospital in Australia from December 2017 to December 2018. PATIENTS: We studied 34 adult patients (70.6% men) undergoing cardiac surgery requiring CPB and a reference group of 36 patients undergoing non-cardiac surgical procedures under general anaesthesia. MAIN OUTCOME MEASURES: We measured SctO2 at baseline, during and after surgery, and then once daily until hospital discharge, for a maximum of 7 days. We used multivariate linear mixed-effects modelling to adjust for all relevant imbalances between the two groups. RESULTS: In the cardiac surgery group, SctO2 was 63.7% [95% confidence interval (CI), 62.0 to 65.5] at baseline and 61.0% (95% CI, 59.1 to 62.9, P = 0.01) on arrival in the ICU. From day 2 to day 7 after cardiac surgery, SctO2 progressively declined. At hospital discharge, SctO2 was significantly lower than baseline, at 53.5% (95% CI, 51.8 to 55.2, P < 0.001). In the reference group, postoperative SctO2 was not significantly different from baseline. On multivariable analysis, cardiac surgery, peripheral vascular disease and time since the operation were associated with greater cerebral desaturation, whereas higher haemoglobin concentrations were associated with slightly better cerebral oxygenation. CONCLUSION: After cardiac surgery on CPB, but not after non-cardiac surgery, most patients experience prolonged cerebral desaturation. Such postoperative desaturation remained unresolved 7 days after surgery. The underlying mechanisms and time to resolution of such cerebral desaturations require further investigation.

Small, short-term, point-of-care creatinine changes as predictors of acute kidney injury in critically ill patients.

PURPOSE: To assess short-term creatinine changes as predictors of acute kidney injury (AKI) when used alone and in combination with AKI risk factors. METHODS: In this prospective cohort study, we identified all creatinine measurements from frequent point-of-care arterial blood gas measurements from ICU admission until AKI. We evaluated the predictive value of small changes between these creatinine measurements for AKI development, alone and with AKI risk factors. RESULTS: Of 377 patients with 3235 creatinine measurements, generating 15,075 creatinine change episodes, 215 (57%) patients developed AKI, and 68 (18%) developed stage 2 or 3 AKI. In isolation, a creatinine increase over 4.1-7.3 h had a 0.65 area under the curve for predicting stage 2 or 3 AKI within 3-37.7 h. Combining creatinine increases of ≥1 µmol/L/h (≥0.0113 mg/dL/h) over 4-5.8 h with three AKI risk factors (cardiac surgery, use of vasopressors, chronic liver disease) had 83% sensitivity, 79% specificity and 0.87 area under the curve for stage 2 or 3 AKI occurring 8.7-25.6 h later. CONCLUSION: In combination with key risk factors, frequent point-of-care creatinine assessment on arterial blood gases to detect small, short-term creatinine changes provides a robust, novel, low-cost, and rapid method for predicting AKI in critically ill patients.

Risk prediction for severe acute kidney injury by integration of urine output, glomerular filtration, and urinary cell cycle arrest biomarkers.

BACKGROUND: Frequent assessment of urine output (UO), serum creatinine (sCr) and urinary cell cycle arrest biomarkers (CCAB) may improve acute kidney injury (AKI) prediction. OBJECTIVE: To study the performance of UO, short term sCr changes and urinary CCAB to predict severe AKI. METHODS: We measured 6 hours of UO, 6-hourly sCr changes, and urinary CCABs in all critically ill patients with cardiovascular or respiratory failure or early signs of renal stress between February and October 2018. We studied the association of such measurements, and their combination, with the development of AKI Stage 2 or 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) definition at 12 hours. We evaluated predictive performance with logistic regression, area under the receiver operating characteristic (AUROC) curve, and net reclassification indices. We computed an optimal cut-off value for each biomarker. RESULTS: We assessed 622 patients and, as per the exclusion criteria, we enrolled 105 critically ill patients. After 12 hours of enrolment, AKI occurred in 32 patients (30%). UO, sCr change over 6 hours and CCABs were significantly associated with severe AKI at 12 hours, with all variables achieving an AUROC > 0.7 after adjustment. Combination of any of the two or three variables achieved an AUROC > 0.7 for subsequent severe AKI at 12 hours. The optimal predictive high specificity cut-off values were ≤ 0.4 mL/kg/h for UO, variation of +15 µmol/L over 6 hours in sCr, and ≥ 1.5 (ng/mL)2/1000 for CCABs. CONCLUSION: In this prospective study, an integrative approach using UO, short term sCr change and/or urinary CCABs showed a satisfactory performance for the prediction of severe AKI development at 12 hours.

The incidence, characteristics, outcomes and associations of small short-term point-of-care creatinine increases in critically ill patients.

PURPOSE: We assessed the incidence, characteristics, outcomes and associations of small, short-term point-of-care creatinine increases in critically ill patients. METHODS: We prospectively identified the first episode of small (>1 µmol/L/h) short-term (3-4 h) point-of-care creatinine increase between two sequential arterial blood gas measurements. We followed patients for the subsequent development of Kidney Disease: Improving Global Outcomes (KDIGO) defined acute kidney injury (AKI) in the intensive care unit (ICU). RESULTS: Of 387 patients, 279 (72.1%) developed an episode of small short-term point-of-care creatinine increase and 212 (54.8%) developed AKI. Such episodes occurred at a median of 5 (IQR 2-10) hours after ICU admission, while AKI occurred at a median of 15 (IQR 9-28) hours after admission. Patients with such episodes were more likely to be mechanically ventilated on admission (83.9 vs. 44.4%; p < .001) and had higher hospital mortality (10.9 vs. 3.7%, p = .03). Creatinine increase episodes had a sensitivity of 86% (95% CI 78-95) and specificity of 31% (95% CI 26-36) for subsequent AKI stages 2 and 3 in 24 h. CONCLUSIONS: Small, short-term point-of-care creatinine increase episodes are common. They are associated with illness severity, occur early, precede AKI by 10 h and are sensitive rather than specific markers of AKI.

The incidence, predictors and outcomes of QTc prolongation in critically ill patients.

PURPOSE: To study the incidence, predictors and outcomes of QTc prolongation (≥500 ms) during ICU admission. METHODS: Prospective observational study of patients admitted to a tertiary ICU during a two-month period. We obtained daily data on QTc intervals and arrhythmias from ICU monitors. We performed univariate and multivariable analyses to compare patients who did or did not experience QTc prolongation. RESULTS: Of the 257 patients, 93 (36.2%) developed ≥1 episode of QTc ≥500 ms. Such patients had higher APACHE II scores (p < .001), received more QT-prolonging medications (p = .002), and more frequently developed non-sustained (<8 beats, p = .007) and sustained ventricular tachycardia (≥8 beats; p < .001). However, after adjustment for confounders, there was no independent association between QTc duration and odds of ventricular tachyarrhythmia (OR = 0.921 [0.593-1.431], p = .715). Moreover, 98% of ventricular tachyarrhythmias resolved spontaneously. Patients with QTc prolongation had longer ICU (p < .001) and hospital length-of-stay (p = .002), and greater ICU (p = .030) and in-hospital mortality (p = .015). No patient experienced sustained Torsades de Pointes or died from ventricular arrhythmia. CONCLUSIONS: A QTc ≥500 ms likely represents a marker of illness severity modulated by several risk factors, and carries no independent association with clinically-significant ventricular tachyarrhythmias. Thus, cessation of QT-prolonging medications to prevent arrhythmias may lack clinical benefit.

Sepsis uncouples serum C-peptide and insulin levels in critically ill patients with type 2 diabetes mellitus.

OBJECTIVE: To assess the effects of sepsis and exogenous insulin on C-peptide levels and C-peptide to insulin ratios in intensive care unit (ICU) patients with type 2 diabetes mellitus (T2DM). DESIGN, SETTING AND PARTICIPANTS: In this prospective, observational, single-centre study, we enrolled 31 ICU-admitted adults with T2DM. We measured serum C-peptide and insulin levels during the first 3 days of ICU stay and recorded characteristics of exogenous insulin therapy. Patients were compared on the basis of the presence of sepsis, and their exposure to exogenous insulin therapy. C-peptide levels were also measured in eight healthy subjects. MAIN OUTCOME MEASURES: Serum insulin and C-peptide levels during the first 3 days in ICU. RESULTS: Median C-peptide levels were higher in the ICU population compared with healthy subjects (10.9 [IQR, 8.2 -14.1] v 4.8 [IQR, 4.6-5.1] nmol/L, P < 0.01). Sepsis was present in 25 ICU patients (81%). Among ICU patients unexposed to exogenous insulin, the 11 patients with sepsis had higher median C-peptide levels compared with the six non-septic patients (2.5 [IQR, 1.8-3.7] v 1.7 [IQR, 0.8-2.2] nmol/L, P = 0.04), and a threefold higher C-peptide to insulin ratio (45 [IQR, 37-62] v 13 [IQR, 11-17], P = 0.03). However, septic patients exposed to exogenous insulin had lower median C-peptide levels (1.2 [IQR, 0.7-2.3] nmol/L, P = 0.01) and C-peptide to insulin ratios (5 [IQR, 2-10], P < 0.01) compared with insulin-free septic patients. The C-peptide to insulin ratio was significantly associated with white cell count and severity of illness in insulin-free septic patients. CONCLUSION: C-peptide levels were elevated in critically ill patients with T2DM. In this population, sepsis increased C-peptide levels and uncoupled serum C-peptide and insulin levels. Exogenous insulin decreased both C-peptide levels and C-peptide to insulin ratios.