Ellen McDonald

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.)

A randomized trial of daily awakening in critically ill patients managed with a sedation protocol: a pilot trial.

Objective:Protocolized sedation (PS) and daily sedative interruption (DI) in critically ill patients have both been shown to shorten the durations of mechanical ventilation (MV) and intensive care unit (ICU) stay. Our objective was to determine the safety and feasibility of a randomized trial to determine whether adults managed with both PS + DI have a shorter duration of MV than patients managed with PS alone. Design:Prospective randomized, concealed, unblinded, multicenter, pilot trial. Setting:Three university-affiliated medical-surgical ICUs. Patients:Sixty-five adults anticipated to require MV >48 hrs and receiving sedative/analgesic infusions. Interventions:Patients were randomized to PS alone, or PS + DI. PS was implemented by bedside nurses; sedatives/analgesics were titrated to achieve Sedation Agitation Score (SAS) 3–4. The PS + DI group also had infusions interrupted daily until the patients awoke. Measurements and Main Results:Diagnosis, age [mean ± sd] (53 ± 18.3 vs. 62.1 ± 16.7 yrs) and Acute Physiology and Chronic Health Evaluation II (27.7 ± 8.4 vs. 26.6 ± 8.4) were similar in the PS and PS + DI groups, respectively. The median duration of MV in the PS and PS + DI groups was 8.0 vs. 10.5 days, and ICU stay was 10.0 vs. 13.0 days, respectively. The SAS was within target range (3–4) in 59% of 9,611 measurements, and within an acceptable range (2–5) in 86% of measurements. Self-assessed nursing and respiratory therapist workload was low in the majority of the cohort. Adverse events were similar in both groups. Patient recruitment was slower than projected (1.5 patients/mo). Conclusion:This pilot trial comparing PS vs. PS + DI confirmed the safety and acceptability of the sedation protocol and DI, and guided important modifications to the protocol, thus enhancing the feasibility of a future multicenter trial. This trial was not designed to detect small but significant differences in clinically important outcomes.

A randomized, controlled trial comparing thoracoscopy and limited thoracotomy for lung biopsy in interstitial lung disease

BACKGROUND Lung biopsies are frequently needed to diagnose diffuse interstitial lung diseases. A prospective randomized, controlled trial comparing limited thoracotomy (open lung biopsy) and thoracoscopy for lung biopsy was done. METHODS Ambulatory patients with a clinical diagnosis of diffuse interstitial lung disease were randomized to thoracoscopy or limited thoracotomy. Data on postoperative pain, narcotic requirements, operating room time, adequacy of biopsy, duration of chest tube drainage, length of hospital stay, spirometry, and complications were collected. RESULTS A total of 42 randomized patients underwent lung biopsy (thoracoscopy 20, thoracotomy 22). The two study groups were comparable with respect to age, gender, corticosteroid use, and preoperative spirometry. Visual analog scale pain scores were nearly identical in the two groups (p = 0.397). Total morphine dose was 50.8 +/- 27.3 mg in the thoracoscopy group and 52.5 +/- 25.6 mg in the thoracotomy group (p = 0.86). Spirometry (FEV1) values in the two groups were not significantly different on postoperative days 1, 2, 14, and 28 (p = 0.665). Duration of operation was similar in both groups (thoracoscopy 40 +/- 30 minutes, thoracotomy 37 +/- 15 minutes; p = 0.67). The thoracoscopy and thoracotomy groups had equivalent duration of chest tube drainage (thoracoscopy 38 +/- 28 hours, thoracotomy 31 +/- 26 hours; p = 0.47) and length of hospital stay (thoracoscopy 77 +/- 82 hours, thoracotomy 69 +/- 55 hours; p = 0.72). Definitive pathologic diagnoses were made in all patients. CONCLUSIONS There is no clinical or statistical difference in outcomes for thoracoscopic and thoracotomy approaches. Both thoracoscopy and thoracotomy are acceptable procedures for diagnostic lung biopsy in diffuse interstitial lung disease.

Minimizing errors of omission: Behavioural rEenforcement of Heparin to Avert Venous Emboli : The BEHAVE study

Objective:To improve patient safety by increasing heparin thromboprophylaxis for medical-surgical intensive care unit patients using a multiple-method approach to evidence-based guideline development and implementation. Design:Prospective longitudinal observational study. Setting:Medical-surgical intensive care unit. Participants:Multidisciplinary clinicians caring for critically ill patients in a 15-bed medical-surgical closed intensive care unit. Interventions:Phase 1 was a 3-month baseline period during which we documented anticoagulation and mechanical thromboprophylaxis. Phase 2 was a 1-yr period in which we implemented a thromboprophylaxis guideline using a) interactive multidisciplinary educational in-services; b) verbal reminders to the intensive care unit team; c) computerized daily nurse recording of thromboprophylaxis; d) weekly graphic feedback to individual intensivists on guideline adherence; and e) publicly displayed graphic feedback on group performance. Phase 3 was a 3-month follow-up period 10 months later, during which we documented thromboprophylaxis. Computerized daily nurse recording of thromboprophylaxis continued in this period. Measurements and Main Results:Intensive care unit and hospital mortality rates were similar across phases, although patients in phase 2 had higher Acute Physiology and Chronic Health Evaluation II scores than patients in phases 1 and 3. The proportion (median % [interquartile range]) of intensive care unit patient-days of heparin thromboprophylaxis in phases 1, 2, and 3 was 60.0 (0, 100), 90.9 (50, 100), and 100.0 (60, 100), respectively (p = .01). The proportion (median % [interquartile range]) of days during which heparin thromboprophylaxis was omitted in error in phases 1, 2, and 3 was 20 (0, 53.8), 0 (0, 6.3), and 0 (0, 0), respectively (p < .001). Conclusions:After development and implementation of an evidence-based thromboprophylaxis guideline, we found significantly more patients receiving heparin thromboprophylaxis. Guideline adherence was maintained 1 yr later. Further research is needed on which are the most effective strategies to implement patient safety initiatives in the intensive care unit.

Detecting myocardial infarction in critical illness using screening troponin measurements and ECG recordings

IntroductionTo use screening cardiac troponin (cTn) measurements and electrocardiograms (ECGs) to determine the incidence of elevated cTn and of myocardial infarction (MI) in patients admitted to the intensive care unit (ICU), and to assess whether these findings influence prognosis. This is a prospective screening study.Materials and methodsWe enrolled consecutive patients admitted to a general medical-surgical ICU over two months. All patients underwent systematic screening with cTn measurements and ECGs on ICU admission, then daily for the first week in ICU, alternate days for up to one month and weekly thereafter until ICU death or discharge, for a maximum of two months. Patients without these investigations ordered during routine clinical care underwent screening for study purposes but these results were unavailable to the ICU team. After the study, all ECGs were interpreted independently in duplicate for ischaemic changes meeting ESC/ACC criteria supporting a diagnosis of MI. Patients were classified as having MI (elevated cTn and ECG evidence supporting diagnosis of MI), elevated cTn only (no ECG evidence supporting diagnosis of MI), or no cTn elevation.ResultsOne hundred and three patients were admitted to the ICU on 112 occasions. Overall, 37 patients (35.9 per cent) had an MI, 15 patients (14.6 per cent) had an elevated cTn only and 51 patients (49.5 per cent) had no cTn elevation. Patients with MI had longer duration of mechanical ventilation (p < 0.0001), longer ICU stay (p = 0.001), higher ICU mortality (p < 0.0001) and higher hospital mortality (p < 0.0001) compared with those with no cTn elevation. Patients with elevated cTn had higher hospital mortality (p = 0.001) than patients without cTn elevation. Elevated cTn was associated with increased hospital mortality (odds ratio 27.3, 95 per cent CI 1.7 – 449.4), after adjusting for APACHE II score, MI and advanced life support. The ICU team diagnosed 18 patients (17.5 per cent) as having MI on clinical grounds; four of these patients did not have MI by adjudication. Thus, screening detected an additional 23 MIs not diagnosed in practice, reflecting 62.2 per cent of MIs ultimately diagnosed. Patients with MI diagnosed by the ICU team had similar outcomes to patients with MI detected by screening alone.ConclusionSystematic screening detected elevated cTn measurements and MI in more patients than were found in routine practice. Elevated cTn was an independent predictor of hospital mortality. Further research is needed to evaluate whether screening and subsequent treatment of these patients reduces mortality.

Research Recruitment Practices and Critically Ill Patients. A Multicenter, Cross-Sectional Study (The Consent Study)

RATIONALE Limited cross-sectional data exist to characterize the challenges of enrolling critically ill patients into research studies. OBJECTIVES We aimed to describe recruitment practices, document factors that impact recruitment, and identify factors that may enhance future research feasibility. METHODS We conducted a prospective, observational study of all critically ill adults eligible to participate in research studies at 23 Canadian intensive care units. We characterized eligibility events into one of five consent outcomes, identified reasons why opportunities to recruit were missed or infeasible, and documented decision makers rationale for providing or declining consent. MEASUREMENTS AND MAIN RESULTS Patients made decisions for themselves in 8.9% of encounters. In 452 eligibility events, consent was not required in 14 (3.1%), missed in 130 (28.8%), infeasible due to operational reasons in 129 (28.5%), obtained in 140 (31.0%), and declined in 39 (8.6%). More than half (57.3%) of all opportunities to recruit patients were missed or infeasible, largely because of research team workload, limited availability, narrow time windows for inclusion, difficulties in contacting families, nonexistent substitute decision makers (SDMs), physician refusals, and protocols prohibiting coenrollment. The rationale for providing consent differed between patients and SDMs. Greater research coordinator experience and site research volume and broader time windows for inclusion were significant predictors of fewer declined consents. CONCLUSIONS A large gap exists between eligibility and the frequency with which consent encounters occur in intensive care unit research. Recruitment is susceptible to design and procedural inefficiencies that hinder recruitment and to personnel availability, given the need to interact with SDMs. Current enrollment practices may underrepresent potential study populations.

DNR directives are established early in mechanically ventilated intensive care unit patients

PurposeSetting treatment goals in the intensive care unit (ICU) often involves resuscitation decisions. Our objective was to study the rate of establishing do-not-resuscitate (DNR) directives, determinants, and outcomes of those directives for mechanically ventilated patients.MethodsIn a multicentre observational study, we included consecutive adults with no DNR directives within 24 hr of ICU admission who were mechanically ventilated for at least 48 hr. We identified the rate with which DNR directives were established, and factors associated with these directives.ResultsAmong 765 patients, DNR directives were established for 231 (30.2%) patients; 143 (62.1%) of these were established within the first week. Factors independently associated with a DNR directive were: patient age [> 75 yr (hazard ratio [HR] 2.3, 95% confidence interval 1.5–3.4], 65 to 74yr(HR 1.8, 1.2–2.7), 50 to 64 yr (HR 1.4, 1.0–2.2) relative to < 50 yr); medical rather than surgical diagnosis (HR 1.8, 1.3–2.5); multiple organ dysfunction score (HR 1.7 for each five-point increment, 1.4–2.0); physician prediction of ICU survival [< 10% (HR 15.0, 6.7–33.6)], 10 to 40% [(HR 5.0, 2.3–11.2), 41 to 60% (HR 4.0, 1.8–9.0) relative to > 90%]; and physician perception of patient preference to limit life support (no advanced life support [(HR 5.8, 3.6–9.4) or partial advanced life support (HR 3.2, 2.2–4.6) compared to full measures].ConclusionOne third of mechanically ventilated patients had DNR directives established early during their ICU stay after the first 24 hr of admission. The strongest predictors of DNR directives were physician prediction of low probability of survival, physician perception of patient preference to limit life support, organ dysfunction, medical diagnosis and age.RésuméObjectifLe choix des objectifs de traitement à l’unité des soins intensifs (USI) comprend souvent des décisions concernant la réanimation. Notre but était d’étudier le taux d’ordonnance «pas de réanimation» (PDR), les déterminants et les conséquences de ces directives pour tes patients ventiiés mécaniquement.MéthodeLors d’une étude par observation muiticentrique, nous avons indus des adultes pour qui la directive PDR avait été émise au cours des 24 premières heures de présence à l’USI et qui étaient sous ventiiation mécanique depuis au moins 48 h. Nous avons déterminé te taux de directives PDR étabiies et ies facteurs qui y sont associés.RésultatsParmi 765 patients, il y a eu des directives PDR dans 231 (30,2 %) des cas; 143 (62,1 %) d’entre elles à l’intérieur de la première semaine. Les facteurs indépendamment associés à la directive PDR ont été : l’âge du patient [ = 75 ans (risque relatif [RR] de 2,3, intervalle de confiance de 95 % 1,5-3,4], 65 à 74 ans (RR de 1,8, 1,2–2,7), 50 à 64 ans (RR de 1,4, 1,0-2,2) par rapport à < 50 ans) ; le diagnostic médical plutôt que chirurgical (RR de 1,8, 1,3-2,5) ; le score de défaillance multiviscérale (RR de 1,7 pour chaque palier de cinq points, 1,4–2,0); la prédiction de survie à l’USI selon le médecin [< 10 % (RR de 15,0, 6,7- 33,6)], 10 à 40 % [(RR de 5,0, 2,3–11,2), 41 à 60% (RRde 4,0, 1,8–9,0) par rapport à > 90%] ; la perception du médecin de la préférence du patient face aux limites du maintien de la vie (par de maintien poussé [(RR de 5,8, 3,6–9,4) ou maintien poussé partiel (RR de 3,2, 2,2–4,6) comparé aux pleines mesures].ConclusionDes directives PDR sont établies tôt pendant le séjour à l’USI, 24 h ou plus après l’admission, chez un tiers des patients ventilés mécaniquement. Les prédicteurs les plus puissants de directives PDR sont la prédiction du médecin d’une faible probabilité de survie, la perception du médecin de la préférence du patient face à la limite du maintien de la vie, la dysfonction organique, le diagnostic médical et l’âge.

A multifaceted strategy to reduce inappropriate use of frozen plasma transfusions in the intensive care unit

PURPOSE The purpose of this study is to determine the effect of a multifaceted behavior-change strategy on inappropriate use of frozen plasma (FP) transfusions in the intensive care unit (ICU). MATERIALS AND METHODS A prospective, time-series study was conducted in a 15-bed medical-surgical ICU in 3 phases: (1) baseline observation; (2) educational campaign, audit and feedback to prescribers, and implementation of an FP request form; and (3) FP request form only. Independently, in triplicate and blinded to study phase, appropriateness of each FP request was adjudicated based on published guidelines and clinical context. RESULTS Over the 15-month study period, 626 FP transfusions (210 FP requests) were administered to 88 patients. Inappropriate FP requests decreased slightly from phases I to III (60% vs 46%; P = .09), FP requests that were consistent with the guidelines did not change (23% vs 22%; P = .86), and FP requests that were appropriate for the ICU yet inconsistent with the guidelines increased (17% vs 32%; P = .04). Although uptake of the FP request form decreased in phase III, it was associated with fewer inappropriate transfusions. CONCLUSIONS The behavior-change strategy modestly improved appropriate use of FP transfusions in the ICU. Improving FP request form accuracy, completeness, and compliance may be required to achieve maximum effect and ensure sustainability.

Lung Volume Reduction for Emphysema and The Canadian Lung Volume Reduction (CLVR) Surgery Project

OBJECTIVE: To review the literature on the surgical treatment of emphysema and to present preliminary results from a pilot study of lung volume reduction (LVR) surgery.

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.