Denise Foster

Intensive versus conventional glucose control in critically ill patients

BACKGROUND The optimal target range for blood glucose in critically ill patients remains unclear. METHODS Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.)

Using the relationship between brain tissue regional saturation of oxygen and mean arterial pressure to determine the optimal mean arterial pressure in patients following cardiac arrest: A pilot proof-of-concept study☆

INTRODUCTION Prospectively assess cerebral autoregulation and optimal mean arterial pressure (MAPOPT) using the dynamic relationship between MAP and regional saturation of oxygen (rSO2) using near-infrared spectroscopy. METHODS Feasibility study of twenty patients admitted to the intensive care unit following a cardiac arrest. All patients underwent continuous rSO2 monitoring using the INVOS(®) cerebral oximeter. ICM+(®) brain monitoring software calculates the cerebral oximetry index (COx) in real-time which is a moving Pearson correlation coefficient between 30 consecutive, 10-s averaged values of MAP and correspond rSO2 signals. When rSO2 increases with increasing MAP (COx ≥0.3), cerebral autoregulation is dysfunctional. Conversely, when rSO2 remains constant or decreases with increasing MAP (COx <0.3), autoregulation is preserved. ICM+(®) fits a U-shaped curve through the COx values plotted vs. MAP. The MAPOPT is nadir of this curve. RESULTS The median age was 59 years (IQR 54-67) and 7 of 20 were female. The cardiac arrest was caused by myocardial infarction in 12 (60%) patients. Nineteen arrests were witnessed and return of spontaneous circulation occurred in a median of 15.5min (IQR 8-33). Patients underwent a median of 30h (IQR 23-46) of monitoring. COx curves and MAPOPT were generated in all patients. The mean overall MAP and MAPOPT were 76mmHg (SD 10) and 76mmHg (SD 7), respectively. MAP was outside of 5mmHg from MAPOPT in 50% (SD 15) of the time. Out of the 7672 5-min averaged COx measurements, 1182 (15%) were at 0.3 or above, indicating absence of autoregulation. Multivariable polynomial fractional regression demonstrated an increase in COx with increasing temperature (P=0.008). CONCLUSIONS We demonstrated the feasibility to determine a MAPOPT using cerebral oximetry in patients after cardiac arrest.

Rates and determinants of informed consent: A case study of an international thromboprophylaxis trial

BACKGROUND Successful completion of randomized trials depends upon efficiently and ethically screening patients and obtaining informed consent. Awareness of modifiable barriers to obtaining consent may inform ongoing and future trials. OBJECTIVE The objective of this study is to describe and examine determinants of consent rates in an international heparin thromboprophylaxis trial (Prophylaxis for ThromboEmbolism in Critical Care Trial, clinicaltrials.gov NCT00182143). DESIGN Throughout the 4-year trial, research personnel approached eligible critically ill patients or their substitute decision makers for informed consent. Whether consent was obtained or declined was documented daily. SETTING The trial was conducted in 67 centers in 6 countries. MEASUREMENTS AND MAIN RESULTS A total of 3764 patients were randomized. The overall consent rate was 82.2% (range, 50%-100%) across participating centers. Consent was obtained from substitute decision makers and patients in 90.1% and 9.9% of cases, respectively. Five factors were independently associated with consent rates. Research coordinators with more experience achieved higher consent rates (odds ratio [OR], 3.43; 95% confidence interval, 2.42-4.86; P < .001 for those with >10 years of experience). Consent rates were higher in smaller intensive care units with less than 15 beds compared with intensive care units with 15 to 20 beds, 21 to 25 beds, and greater than 25 beds (all ORs, <0.5; P < .001) and were higher in centers with more than 1 full-time research staff (OR, 1.95; 95% confidence interval, 1.28-2.99; P < .001). Consent rates were lower in centers affiliated with the Canadian Critical Care Trials Group or the Australian and New Zealand Intensive Care Society Clinical Trials Group compared with other centers (OR, 0.57; 95% confidence interval, 0.42-0.77; P < .001). Finally, consent rates were highest during the pilot trial, lowest during the initiation of the full trial, and increased over years of recruitment (P < .001). CONCLUSIONS Characteristics of study centers, research infrastructure, and experience were important factors associated with successfully procuring informed consent to participate in this thromboprophylaxis trial.

Thromboprophylaxis patterns and determinants in critically ill patients: a multicenter audit

IntroductionHeparin is safe and prevents venous thromboembolism in critical illness. We aimed to determine the guideline concordance for thromboprophylaxis in critically ill patients and its predictors, and to analyze factors associated with the use of low molecular weight heparin (LMWH), as it may be associated with a lower risk of pulmonary embolism and heparin-induced thrombocytopenia without increasing the bleeding risk.MethodsWe performed a retrospective audit in 28 North American intensive care units (ICUs), including all consecutive medical-surgical patients admitted in November 2011. We documented ICU thromboprophylaxis and reasons for omission. Guideline concordance was determined by adding days in which patients without contraindications received thromboprophylaxis to days in which patients with contraindications did not receive it, divided by the total number of patient-days. We used multilevel logistic regression including time-varying, center and patient-level covariates to determine the predictors of guideline concordance and use of LMWH.ResultsWe enrolled 1,935 patients (62.3 ± 16.7 years, Acute Physiology and Chronic Health Evaluation [APACHE] II score 19.1 ± 8.3). Patients received thromboprophylaxis with unfractionated heparin (UFH) (54.0%) or LMWH (27.6%). Guideline concordance occurred for 95.5% patient-days and was more likely in patients who were sicker (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.17, 1.75 per 10-point increase in APACHE II), heavier (OR 1.32, 95% CI 1.05, 1.65 per 10-m/kg2 increase in body mass index), had cancer (OR 3.22, 95% CI 1.81, 5.72), previous venous thromboembolism (OR 3.94, 95% CI 1.46,10.66), and received mechanical ventilation (OR 1.83, 95% CI 1.32,2.52). Reasons for not receiving thromboprophylaxis were high risk of bleeding (44.5%), current bleeding (16.3%), no reason (12.9%), recent or upcoming invasive procedure (10.2%), nighttime admission or discharge (9.7%), and life-support limitation (6.9%). LMWH was less often administered to sicker patients (OR 0.65, 95% CI 0.48, 0.89 per 10-point increase in APACHE II), surgical patients (OR 0.41, 95% CI 0.24, 0.72), those receiving vasoactive drugs (OR 0.47, 95% CI 0.35, 0.64) or renal replacement therapy (OR 0.10, 95% CI 0.05, 0.23).ConclusionsGuideline concordance for thromboprophylaxis was high, but LMWH was less commonly used, especially in patients who were sicker, had surgery, or received vasopressors or renal replacement therapy, representing a potential quality improvement target.

Critical care capacity in Canada: results of a national cross-sectional study

IntroductionIntensive Care Units (ICUs) provide life-supporting treatment; however, resources are limited, so demand may exceed supply in the event of pandemics, environmental disasters, or in the context of an aging population. We hypothesized that comprehensive national data on ICU resources would permit a better understanding of regional differences in system capacity.MethodsAfter the 2009–2010 Influenza A (H1N1) pandemic, the Canadian Critical Care Trials Group surveyed all acute care hospitals in Canada to assess ICU capacity. Using a structured survey tool administered to physicians, respiratory therapists and nurses, we determined the number of ICU beds, ventilators, and the ability to provide specialized support for respiratory failure.ResultsWe identified 286 hospitals with 3170 ICU beds and 4982 mechanical ventilators for critically ill patients. Twenty-two hospitals had an ICU that routinely cared for children; 15 had dedicated pediatric ICUs. Per 100,000 population, there was substantial variability in provincial capacity, with a mean of 0.9 hospitals with ICUs (provincial range 0.4-2.8), 10 ICU beds capable of providing mechanical ventilation (provincial range 6–19), and 15 invasive mechanical ventilators (provincial range 10–24). There was only moderate correlation between ventilation capacity and population size (coefficient of determination (R2) = 0.771).ConclusionICU resources vary widely across Canadian provinces, and during times of increased demand, may result in geographic differences in the ability to care for critically ill patients. These results highlight the need to evolve inter-jurisdictional resource sharing during periods of substantial increase in demand, and provide background data for the development of appropriate critical care capacity benchmarks.

Enhancing the informed consent process for critical care research: Strategies from a thromboprophylaxis trial

BACKGROUND Critically ill patients lack capacity for decisions about research participation. Consent to enrol these patients in studies is typically obtained from substitute decision-makers. OBJECTIVE To present strategies that may optimise the process of obtaining informed consent from substitute decision-makers for participation of critically ill patients in trials. We use examples from a randomised trial of heparin thromboprophylaxis in the intensive care unit (PROTECT, clinicaltrials.gov NCT00182143). METHODS 3764 patients were randomised, with an informed consent rate of 82%; 90% of consents were obtained from substitute decision-makers. North American PROTECT research coordinators attended three meetings to discuss enrolment: (1) Trial start-up (January 2006); (2) Near trial closure (January 2010); and (3) Post-publication (April 2011). Data were derived from slide presentations, field notes from break-out groups and plenary discussions, then analysed inductively. RESULTS We derived three phases for the informed consent process: (1) Preparation for the Consent Encounter; (2) The Consent Encounter; and (3) Follow-up to the Consent Encounter. Specific strategies emerged for each phase: Phase 1 (four strategies); Phase 2 (six strategies); and Phase 3 (three strategies). CONCLUSION We identified 13 strategies that may improve the process of obtaining informed consent from substitute decision-makers and be generalisable to other settings and studies.

Barriers and facilitators of thromboprophylaxis for medical-surgical intensive care unit patients: a multicenter survey.

BACKGROUND The objective of this study was to identify the self-reported barriers to and facilitators of prescribing low-molecular-weight heparin (LMWH) thromboprophylaxis in the intensive care unit (ICU). METHODS We conducted an interviewer-administered survey of 4 individuals per ICU (the ICU director, a bedside pharmacist, a thromboprophylaxis research coordinator, and physician site investigator) regarding LMWH thromboprophylaxis for medical-surgical patients in 27 ICUs in Canada and the United States. Items were generated by the research team and adapted from previous surveys, audits, qualitative studies, and quality improvement research. Respondents rated the barriers to LMWH use, facilitators (effectiveness, affordability, and acceptability thereof), and perceptions regarding LMWH use. RESULTS Respondents had 14.5 (SD, 7.7) years of ICU experience (response rate, 99%). The 5 most common barriers in descending order were as follows: drug acquisition cost, fear of bleeding, lack of resident education, concern about bioaccumulation in renal failure, and habit. The top 5 rated facilitators were preprinted orders, education, daily reminders, audit and feedback, and local quality improvement committee endorsement. Centers using preprinted orders (mean difference [P<.01]) and computerized physician order entry (P<.01) compared with those centers not using those tools reported higher affordability for these 2 facilitators. Compared with physicians and pharmacists, research coordinators considered ICU-specific audit and feedback of thromboprophylaxis rates to be a more effective, acceptable, and affordable facilitator (odds ratio, 6.67; 95% confidence interval, 1.97-22.53; P<.01). Facilitator acceptability ratings were similar within centers but differed across centers (P≤.01). CONCLUSIONS This multicenter survey found several barriers to use of LMWH including cost, concern about bleeding, and lack of resident knowledge of effectiveness. The diversity of reported facilitators suggests that large scale programs may address generic barriers but also need site-specific interprofessional knowledge translation activities.

The screen log: a tool for monitoring critical care clinical research activity.

Clinical research relevant to the care of critically ill patients has been ongoing for decades. Sponsors of research projects monitor site performance by providing a screen log (SL) which contains a record of enrolled patients (multicentre, uni-project in scope). The present study was undertaken to evaluate the utility of a unicentre, multi-project SL.