The hemodynamic effects of warm versus room-temperature crystalloid fluid bolus therapy in post-cardiac surgery patients.

INTRODUCTION: The contribution of fluid temperature to the effect of crystalloid fluid bolus therapy (FBT) in post-cardiac surgery patients is unknown. We evaluated the hemodynamic effects of FBT with fluid warmed to 40°C (warm FBT) versus room-temperature fluid. METHODS: In this single centre prospective before-and-after study, we evaluated the effects of 500 ml of warm versus room-temperature compound sodium lactate administered over <30 minutes, in 50 cardiac surgery patients admitted to ICU. We recorded hemodynamics continuous before and for 30 minutes after the first FBT. We defined CI responsiveness (CI-R) as an CI increase >15% of baseline immediately after FBT and effect dissipation if the CI returned to <5% of baseline and MAP responsiveness as >10% increase and dissipation as return to <3 mmHg of baseline. RESULTS: Hypotension (56%) and low CI (40%) typically triggered FBT. Temperature decreased >0.3°C in 13 (52%) patients after room-temperature FBT versus 0 (0%) after warm FBT (p < 0.01). CI and MAP responsiveness was similar (16 [64%] versus 11 [44%], p = 0.15 and 15 [60%] versus 17 [68%], p = 0.77, respectively). Among CI responders, CI increased more with room-temperature FBT (+0.6 [IQR, 0.5-1.1] versus +0.5 [IQR, 0.4-0.6] L/min/m2, p = 0.01). However, dissipation was more common after room-temperature versus warm FBT (9/16 [56%] versus 1/11 [9%], p = 0.02). CONCLUSION: In postoperative cardiac surgery patients, warm FBT preserved core temperature and induced smaller but more sustained CI increases among responders. Fluid temperature appears to impact both core temperature and the duration of CI response.

Comparison of the Hemodynamic and Temperature Effects of a 500-mL Bolus of 4% Albumin at Room Versus Body Temperature in Cardiac Surgery Patients.

OBJECTIVE: To compare the hemodynamic effect of room temperature (cold) 4% albumin fluid bolus therapy (FBT) with body temperature (warm) albumin FBT. DESIGN: Prospective, before-after trial. SETTING: A tertiary intensive care unit (ICU). PARTICIPANTS: Sixty ventilated, post-cardiac surgery patients prescribed with 4% albumin FBT. INTERVENTION: Cold or warm 4% albumin 500 ml FBT. MEASUREMENTS AND MAIN RESULTS: We recorded hemodynamic parameters before and for 30 minutes after FBT. Cardiac index (CI) and mean arterial pressure (MAP) responses were defined by a CI increase >15% and a MAP increase >10%, respectively. Immediately after FBT, median [interquartile range] core temperature changed by -0.3 [-0.4; -0.3] °C with cold albumin vs. 0.0 [0.0; 0.1]°C with warm albumin (P<0.001). The median CI increase was 0.3 [0.0; 0.5] L/min/m2 with 14 CI-responders (47%) in both groups (P>0.99). The median immediate MAP increase was 9 [3; 15] mmHg with cold albumin vs. 11 [5; 13] mmHg with warm albumin (P=0.79), with a MAP-response in 16 vs. 17 patients (P=0.99). There was an interaction between group and time for MAP (P=0.002), mean pulmonary artery pressure (PAP) (P=0.002) and core temperature (P<0.001). In the cold albumin group, after the initial response, MAP and mean PAP decreased more slowly than with warm albumin and, after the initial fall, core temperature increased toward baseline. CONCLUSION: In postoperative cardiac surgery patients, warm albumin FBT prevents the decrease in core temperature and, after an initial similar increase, is associated with a faster return of MAP and mean PAP toward baseline.

A Pilot Randomized Controlled Study of Mild Hypercapnia During Cardiac Surgery With Cardiopulmonary Bypass.

OBJECTIVES: To test whether targeted therapeutic mild hypercapnia (TTMH) would attenuate cerebral oxygen desaturation detected using near-infrared spectroscopy during cardiac surgery requiring cardiopulmonary bypass (CPB). DESIGN: Randomized controlled trials. SETTING: Operating rooms and intensive care unit of tertiary hospital. PARTICIPANTS: The study comprised 30 patients undergoing cardiac surgery with CPB. INTERVENTIONS: Patients were randomly assigned to receive either standard carbon dioxide management (normocapnia) or TTMH (target arterial carbon dioxide partial pressure between 50 and 55 mmHg) throughout the intraoperative period and postoperatively until the onset of spontaneous ventilation. MEASUREMENTS AND MAIN RESULTS: Relevant biochemical and hemodynamic variables were measured, and cerebral tissue oxygen saturation (SctO2) was monitored with near-infrared spectroscopy. Patients were followed-up with neuropsychological testing. Patient demographics between groups were compared using the Fisher exact and Mann-Whitney tests, and SctO2 between groups was compared using repeated measures analysis of variance. The median patient age was 67 years (interquartile range [IQR] 62-72 y), and the median EuroSCORE II was 1.1. The median CPB time was 106 minutes. The mean intraoperative arterial carbon dioxide partial pressure for each patient was significantly higher with TTMH (52.1 mmHg [IQR 49.9-53.9 mmHg] v 40.8 mmHg [IQR 38.7-41.7 mmHg]; p < 0.001) as was pulmonary artery pressure (23.9 mmHg [IQR 22.4-25.3 mmHg] v 18.5 mmHg [IQR 14.8-20.7 mmHg]; p = 0.004). There was no difference in mean percentage change in SctO2 during CPB in the control group for both hemispheres (left: -6.7% v -2.3%; p = 0.110; right: -7.9% v -1.0%; p = 0.120). Compliance with neuropsychological test protocols was poor. However, the proportion of patients with drops in test score >20% was similar between groups in all tests. CONCLUSIONS: TTMH did not increase SctO2 appreciably during CPB but increased pulmonary artery pressures before and after CPB. These findings do not support further investigation of TTMH as a means of improving SctO2 during and after cardiac surgery requiring CPB.

Liberal Glucose Control in ICU Patients With Diabetes: A Before-and-After Study.

OBJECTIVES: To assess the feasibility, biochemical efficacy, and safety of liberal versus conventional glucose control in ICU patients with diabetes. DESIGN: Prospective, open-label, sequential period study. SETTING: A 22-bed mixed ICU of a tertiary hospital in Australia. PATIENTS: We compared 350 consecutive patients with diabetes admitted over 15 months who received liberal glucose control with a preintervention control population of 350 consecutive patients with diabetes who received conventional glucose control. INTERVENTIONS: Liberal control patients received insulin therapy if glucose was greater than 14 mmol/L (target: 10-14 mmol/L [180-252 mg/dL]). Conventional control patients received insulin therapy if glucose was greater than 10 mmol/L (target: 6-10 mmol/L [108-180 mg/dL]). MEASUREMENTS AND MAIN RESULTS: We assessed separation in blood glucose, insulin requirements, occurrence of hypoglycemia (blood glucose ≤ 3.9 mmol/L [70 mg/dL]), creatinine and white cell count levels, and clinical outcomes. The median (interquartile range) time-weighted average blood glucose concentration was significantly higher in the liberal control group (11.0 mmol/L [8.7-12.0 mmol/L]; 198 mg/dL [157-216 mg/dL]) than in the conventional control group (9.6 mmol/L [8.5-11.0 mmol/L]; 173 mg/dL [153-198 mg/dL]; p < 0.001). Overall, 132 liberal control patients (37.7%) and 188 conventional control patients (53.7%) received insulin in ICU (p < 0.001). Hypoglycemia occurred in 6.6% and 8.6%, respectively (p = 0.32). Among 314 patients with glycated hemoglobin A1c greater than or equal to 7%, hypoglycemia occurred in 4.1% and 9.6%, respectively (p = 0.053). Trajectories of creatinine and white cell count were similar in the groups. In multivariable analyses, we found no independent association between glucose control and mortality, duration of mechanical ventilation, or ICU-free days to day 30. CONCLUSIONS: In ICU patients with diabetes, during a period of liberal glucose control, insulin administration, and among patients with hemoglobin A1c greater than or equal to 7%, the prevalence of hypoglycemia was reduced, without negatively affecting serum creatinine, the white cell count response, or other clinical outcomes. (Trial Registration: Australian New Zealand Clinical Trials Registry; ACTRN12615000216516).

Pharmacokinetics of Magnesium Bolus Therapy in Cardiothoracic Surgery.

OBJECTIVE: To investigate the pharmacokinetics of a 20 mmol magnesium bolus in regards to serum and urinary magnesium concentration, volume of distribution, and half-life. DESIGN: Prospective, experimental study. SETTING: A university-affiliated teaching hospital. PARTICIPANTS: Twenty consecutive cardiac surgery patients treated with magnesium bolus therapy for prevention of arrhythmia. INTERVENTIONS: A 20-mmol bolus of magnesium sulfate was administered intravenously. MEASUREMENTS AND MAIN RESULTS: Median magnesium levels increased from 1.04 (interquartile range 0.94-1.23) mmol/L to 1.72 (1.57-2.14) mmol/L after 60 minutes of magnesium infusion (p < 0.001) but decreased to 1.27 (1.21-1.36) and 1.16 (1.11-1.21) mmol/L after 6 and 12 hours, respectively. Urinary magnesium concentration increased from 6.3 (4.2-14.5) mmol/L to 19.1 (7.4-34.5) mmol/L after 60 minutes (p < 0.001), followed by 22.7 (18.4-36.7) and 15 (8.4-19.7) mmol/L after 6 and 12 hours, respectively. Over the 12-hour observation period, the cumulative urinary magnesium excretion was 19.1 mmol (95.5% of the dose given). The median magnesium clearance was 10 (4.7-15.8) mL/min and increased to 14.9 (3.8-20.7; p = 0.934) mL/min at 60 minutes. The estimated volume of distribution was 0.31 (0.28-0.34) L/kg. CONCLUSION: Magnesium bolus therapy after cardiac surgery leads to a significant but short-lived increase of magnesium serum concentration due to renal excretion and distribution, and the magnesium balance is neutral after 12 hours.

The Open Lung Approach Improves Pulmonary Vascular Mechanics in an Experimental Model of Acute Respiratory Distress Syndrome.

OBJECTIVE: To test whether positive end-expiratory pressure consistent with an open lung approach improves pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressures in experimental acute respiratory distress syndrome. DESIGN: Experimental study. SETTING: Animal research laboratory. SUBJECTS: Ten pigs, 35 ± 5.2 kg. INTERVENTIONS: Acute respiratory distress syndrome was induced combining saline lung lavages with injurious mechanical ventilation. The positive end-expiratory pressure level resulting in highest compliance during a decremental positive end-expiratory pressure trial after lung recruitment was determined. Thereafter, three positive end-expiratory pressure levels were applied in a random order: hyperinflation, 6 cm H2O above; open lung approach, 2 cm H2O above; and collapse, 6 cm H2O below the highest compliance level. High fidelity pressure and flow sensors were placed at the main pulmonary artery for measuring pulmonary artery resistance (Z0), effective arterial elastance, compliance, and reflected pressure waves. MEASUREMENTS AND MAIN RESULTS: After inducing acute respiratory distress syndrome, Z0 and effective arterial elastance increased (from 218 ± 94 to 444 ± 115 dyn.s.cm and from 0.27 ± 0.14 to 0.62 ± 0.22 mm Hg/mL, respectively; p < 0.001), vascular compliance decreased (from 2.76 ± 0.86 to 1.48 ± 0.32 mL/mm Hg; p = 0.003), and reflected waves arrived earlier (0.23 ± 0.07 vs 0.14 ± 0.05, arbitrary unit; p = 0.002) compared with baseline. Comparing the three positive end-expiratory pressure levels, open lung approach resulted in the lowest: 1) Z0 (297 ± 83 vs 378 ± 79 dyn.s.cm, p = 0.033, and vs 450 ± 119 dyn.s.cm, p = 0.002); 2) effective arterial elastance (0.37 ± 0.08 vs 0.50 ± 0.15 mm Hg/mL, p = 0.04, and vs 0.61 ± 0.12 mm Hg/mL, p < 0.001), and 3) reflection coefficient (0.35 ± 0.17 vs 0.48 ± 0.10, p = 0.024, and vs 0.53 ± 0.19, p = 0.005), comparisons with hyperinflation and collapse, respectively. CONCLUSIONS: In this experimental setting, positive end-expiratory pressure consistent with the open lung approach resulted in the best pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressure settings.

Two Different Endoscopic Procedures Made Feasible by the Janus Mask in a High-Risk Patient.

The Janus mask is a full face mask designed for providing noninvasive ventilation (NIV) during any kind of upper endoscopies (e.g., fiber-optic bronchoscopy, gastrointestinal endoscopy, and transesophageal echocardiography). Due to its unique conformation, its use can be considered for both elective and urgent endoscopic procedures in high-risk patients. In this case report, we present a patient with acute respiratory failure who underwent two consecutive different endoscopic procedures (fiber-optic bronchoscopy and gastrointestinal endoscopy) during continuous positive airway pressure support by means of this novel NIV mask, thus avoiding tracheal intubation and at the same time, improving his respiratory condition.

Worldwide Opinion on Multicenter Randomized Interventions Showing Mortality Reduction in Critically Ill Patients: A Democracy-Based Medicine Approach.

OBJECTIVES: Democracy-based medicine is a combination of evidence-based medicine (systematic review), expert assessment, and worldwide voting by physicians to express their opinions and self-reported practice via the Internet. The authors applied democracy-based medicine to key trials in critical care medicine. DESIGN AND SETTING: A systematic review of literature followed by web-based voting on findings of a consensus conference. PARTICIPANTS: A total of 555 clinicians from 61 countries. INTERVENTIONS: The authors performed a systematic literature review (via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter randomized clinical trials in critical care that reported a significant effect on survival and were endorsed by expert clinicians. Then they solicited voting and self-reported practice on such evidence via an interactive Internet questionnaire. Relationships among trial sample size, design, and respondents' agreement were investigated. The gap between agreement and use/avoidance and the influence of country origin on physicians' approach to interventions also were investigated. MEASUREMENTS AND MAIN RESULTS: According to 24 multicenter randomized controlled trials, 15 interventions affecting mortality were identified. Wide variabilities in both the level of agreement and reported practice among different interventions and countries were found. Moreover, agreement and reported practice often did not coincide. Finally, a positive correlation among agreement, trial sample size, and number of included centers was found. On the contrary, trial design did not influence clinicians' agreement. CONCLUSIONS: Physicians' clinical practice and agreement with the literature vary among different interventions and countries. The role of these interventions in affecting survival should be further investigated to reduce both the gap between evidence and clinical practice and transnational differences.

Lung inflammation persists after 27 hours of protective Acute Respiratory Distress Syndrome Network Strategy and is concentrated in the nondependent lung.

OBJECTIVE: PET with [18F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. DESIGN: Prospective laboratory investigation. SETTING: University animal research laboratory. SUBJECTS: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. INTERVENTIONS: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [18F]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. MEASUREMENTS AND MAIN RESULTS: [18F]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. CONCLUSIONS: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.

Nature and impact of in-hospital complications associated with persistent critical illness.

Background: Persistent critical illness (PerCI) is defined as an intensive care unit (ICU) admission lasting ≥ 10 days. The in-hospital complications associated with its development are poorly understood. Aims: To test whether PerCI is associated with a greater prevalence, rate and specific types of in-hospital complications. Methods: Single-centre, retrospective, observational case-control study. Results: We studied 1200 patients admitted to a tertiary ICU from 2010 to 2015. Median ICU length of stay was 16 days (interquartile range [IQR], 12-23) for PerCI patients v 2.3 days (IQR, 1.1-3.7) for controls, and median hospital length of stay was 41 days (IQR, 22-75) v 8 days (IQR, 4-17) respectively. A greater proportion of PerCI patients received acute renal replacement therapy (37% v 6.8%) or underwent reintubation (17% v 1%) and/or tracheostomy (36% v 0.6%); P < 0.0001. Despite these complications, PerCI patients had similar hospital mortality (29% v 27%; P = 0.53). PerCI patients experienced a greater absolute number of complications (12.1 v 4.0 complications per patient; P < 0.0001) but had fewer exposure-adjusted complications (202 v 272 complications per 1000 hospital bed-days; P < 0.001) and a particularly high overall prevalence of specific complications. Conclusions: PerCI patients experience a higher prevalence, but not a higher rate, of exposure-adjusted complications. Some of these complications appear amenable to prevention, helping to define intervention targets in patients at risk of PerCI. Funding: Austin Hospital Intensive Care Trust Fund.

Haemodynamic effect of a 20% albumin fluid bolus in post-cardiac surgery patients.

OBJECTIVE: To study the cardiovascular effect over 30 minutes following the end of fluid bolus therapy (FBT) with 20% albumin in patients after cardiac surgery. DESIGN: Prospective observational study. SETTING: Intensive care unit of a tertiary university-affiliated hospital. PARTICIPANTS: Twenty post-cardiac surgery mechanically ventilated patients with a clinical decision to administer FBT. INTERVENTION: FBT with a 100 mL bolus of 20% albumin. MAIN OUTCOME MEASURES: Cardiac index (CI) response was defined by a ≥ 15% increase, while mean arterial pressure (MAP) response was defined by a ≥ 10% increase. RESULTS: The most common indication for FBT was hypotension (40%). Median duration of infusion was 7 minutes (interquartile range [IQR], 3-9 min). At the end of FBT, five patients (25%) showed a CI response, which increased to almost half in the following 30 minutes and dissipated in one patient. MAP response occurred in 11 patients (55%) and dissipated in five patients (45%) by a median of 6 minutes (IQR, 6-10 min). CI and MAP responses coexisted in four patients (20%). An intrabolus MAP response occurred in 17 patients (85%) but dissipated in 11 patients (65%) within a median of 7 minutes (IQR, 2-11 min). On regression analysis, faster fluid bolus administration predicted MAP increase at the end of the bolus. CONCLUSION: In post-cardiac surgery patients, CI response to 20% albumin FBT was not congruous with MAP response over 30 minutes. Although hypotension was the main indication for FBT and a MAP response occurred in most of patients, such response was maximal during the bolus, dissipated in a few minutes, and was dissociated from the CI response.

Carotid artery and cerebral blood flow during experimental cardiopulmonary resuscitation: A systematic review of the literature.

BACKGROUND: The carotid artery blood flow (CABF) or cerebral blood flow (CBF) achieved with current techniques of cardiac compression in humans are unknown. Animal experiments may provide useful information on such flows and on possible techniques to optimize them. OBJECTIVES: To obtain an estimate of carotid and cerebral blood flows during cardiac compression with different techniques. METHODS: We performed a systematic review of all studies in the English literature that measured the CABF and/or CBF during cardiac compression in experimental models of cardiac arrest, expressed as a percentage of baseline (pre-arrest) values. We compared the effect of vasopressor use, thoracic compression technique, pre-arrest infusion and animal model on maximum blood flows using standard statistical methodologies. RESULTS: Overall, 133 studies were reviewed. Of these, 45 studies provided information only on CABF; 77 only on CBF, and 11 studies on both flows. The overall weighted mean (±SD) CABF was 35.2 ± 27.7% of baseline. Porcine studies showed lower CABF when vasopressors were used (p = 0.0002). Studies of CBF reported a weighted mean value of 66.5 ± 48.5% of baseline. Adjunctive vasopressor therapy significantly increased CBF (p = 0.007), as did fluid administration (P = 0.049). In studies reporting both CABF and CBF, the median CABF/CBF ratio was 0.67 (range 0.21-1.96). CONCLUSIONS: During experimental cardiac compression, compared to baseline, CABF appears to decrease much more than CBF. However results should be regarded with caution. They are affected by ancillary interventions and measurement methods, variability is marked and, in experiments measuring CABF and CBF simultaneously, their ratios range well outside physiologically plausible values.

The performance of flash glucose monitoring in critically ill patients with diabetes.

OBJECTIVE: Frequent glucose monitoring may improve glycaemic control in critically ill patients with diabetes. We aimed to assess the accuracy of a novel subcutaneous flash glucose monitor (FreeStyle Libre [Abbott Diabetes Care]) in these patients. METHODS: We applied the FreeStyle Libre sensor to the upper arm of eight patients with diabetes in the intensive care unit and obtained hourly flash glucose measurements. Duplicate recordings were obtained to assess test-retest reliability. The reference glucose level was measured in arterial or capillary blood. We determined numerical accuracy using Bland- Altman methods, the mean absolute relative difference (MARD) and whether the International Organization for Standardization (ISO) and Clinical and Laboratory Standards Institute Point of Care Testing (CLSI POCT) criteria were met. Clarke error grid (CEG) and surveillance error grid (SEG) analyses were used to determine clinical accuracy. RESULTS: We compared 484 duplicate flash glucose measurements and observed a Pearson correlation coefficient of 0.97 and a coefficient of repeatability of 1.6 mmol/L. We studied 185 flash readings paired with arterial glucose levels, and 89 paired with capillary glucose levels. Using the arterial glucose level as the reference, we found a mean bias of 1.4 mmol/L (limits of agreement, -1.7 to 4.5 mmol/L). The MARD was 14% (95% CI, 12%-16%) and the proportion of measurements meeting ISO and CLSI POCT criteria was 64.3% and 56.8%, respectively. The proportions of values within a low-risk zone on CEG and SEG analyses were 97.8% and 99.5%, respectively. Using capillary glucose levels as the reference, we found that numerical and clinical accuracy were lower. CONCLUSIONS: The subcutaneous FreeStyle Libre blood glucose measurement system showed high test-retest reliability and acceptable accuracy when compared with arterial blood glucose measurement in critically ill patients with diabetes.

The effect of insulin administration on c-peptide in critically ill patients with type 2 diabetes.

BACKGROUND: In critically ill patients with permissive hyperglycemia, it is uncertain whether exogenous insulin administration suppresses or enhances c-peptide secretion (a marker of pancreatic beta-cell response). We aimed to explore this effect in patients with type 2 diabetes. METHODS: We prospectively enrolled a cohort of 45 critically ill patients with type 2 diabetes managed according to a liberal glucose protocol (target blood glucose 10-14 mmol/l). We recorded the administration of insulin and oral hypoglycemic agents and measured plasma c-peptide as surrogate marker of endogenous insulin secretion on the first two consecutive days in ICU. RESULTS: Overall, 20 (44.4%) patients required insulin to achieve target blood glucose. Insulin-treated patients had higher glycated hemoglobin A1c, more premorbid insulin-requiring type 2 diabetes, and greater blood glucose levels but lower c-peptide levels on admission. Premorbid insulin-requiring diabetes was independently associated with lower admission c-peptide, whereas greater plasma creatinine was independently associated with higher levels. Increases in c-peptide were positively correlated with an increase in blood glucose both in patients who did (r = 0.54, P = 0.01) and did not (r = 0.56, P = 0.004) receive insulin. However, insulin administration was independently associated with a greater increase in c-peptide (P = 0.04). This association was not modified by the use of oral insulin secretagogues. CONCLUSIONS: C-peptide, a marker of beta-cell response, responds to and is influenced by glycemia and renal function in critically ill patients with type 2 diabetes. In addition, in our cohort, exogenous insulin administration was associated with a greater increase in c-peptide in response to hyperglycemia. Trial Registration Australian New Zealand Clinical Trials Registry (ACTRN12615000216516).