Alexis F. Turgeon

Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada

CONTEXT Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America. OBJECTIVE To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection. DESIGN, SETTING, AND PATIENTS A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009. MAIN OUTCOME MEASURES The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay. RESULTS Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao(2) to fraction of inspired oxygen [Fio(2)] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29). CONCLUSION Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.

Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study

Background: Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine. Methods: To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale). Results: We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval [CI] 28.4%–35.2%) and ranged from 10.8% to 44.2% across centres (χ2 test for overall difference, p < 0.001). Most deaths (70.2% [160/228], 95% CI 63.9%–75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ2 test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care. Interpretation: We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury.

Erythropoietin-receptor agonists in critically ill patients: a meta-analysis of randomized controlled trials

Introduction: Anemia and the need for red blood cell transfusions are common among patients admitted to intensive care units. Erythropoietin has been used to decrease the need for transfusions; however, its ability to improve clinical outcomes is unknown. We evaluated the effect of erythropoietin-receptor agonists on clinically important outcomes, including mortality, length of stay in hospital or intensive care unit, ventilator use, transfusion requirements and major adverse events. Methods: To identify relevant studies, we searched electronic databases covering 1950 to 2007 (MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the Scopus database). We also searched conference proceedings and grey literature sources. We selected all randomized controlled trials involving critically ill patients that compared an erythropoietin-receptor agonist with a placebo or no intervention. No language restrictions were considered. Data were extracted using a standardized extraction template. We used a fixed effects model to calculate all summary measures of treatment effects. Results: Of 673 identified records, 9 studies that investigated erythropoietin alpha met the eligibility criteria and were included in our analysis. Erythropoietin, compared with placebo or no intervention, had no statistically significant effect on overall mortality (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.71–1.05, I2 = 0%). The treatment and control groups did not differ in the length of stay in hospital or intensive care unit, or in the duration of mechanical ventilation, in the 3 studies that reported these outcomes. Erythropoietin, compared with placebo, significantly reduced the odds of a patient receiving at least 1 transfusion (OR 0.73, 95% CI 0.64–0.84, I2 = 54.7%). The mean number of units of blood transfused per patient was decreased by 0.41 units in the erythropoietin group (95% CI 0.10–0.74, I2 = 79.2%). Most of the included studies were performed before the widespread adoption of a restrictive transfusion strategy. Only 1 study provided detailed reports of adverse events, and none of the studies systematically evaluated all patients for venous thromboembolism. Interpretation: At this time, we do not recommend the routine use of erythropoietin-receptor agonists in critically ill patients. The reduction in red blood cell transfusions per patient was very small, and there is insufficient evidence to determine whether this intervention results in clinically important benefits with acceptable risks.

Cricoid Pressure Does Not Increase the Rate of Failed Intubation by Direct Laryngoscopy in Adults

Background:Cricoid pressure (CP) is applied during induction of anesthesia to prevent regurgitation of gastric content and pulmonary aspiration. However, it has been suggested that CP makes tracheal intubation more difficult. This double-blind randomized study evaluated the effect of CP on orotracheal intubation by direct laryngoscopy in adults. Methods:Seven hundred adult patients undergoing general anesthesia for elective surgery were randomly assigned to have a standardized CP (n = 344) or a sham CP (n = 356) during laryngoscopy and intubation. After anesthesia induction and complete muscle relaxation, a 30-s period was allowed to complete intubation with a Macintosh No. 3 laryngoscope blade. The primary endpoint was the rate of failed intubation at 30 s. The secondary endpoints included the intubation time, the Cormack and Lehane grade of laryngoscopic view, and the Intubation Difficulty Scale score. Results:Groups were similar for demographic data and risk factors for difficult intubation. The rates of failed intubation at 30 s were comparable for the two groups: 15 of 344 (4.4%) and 13 of 356 (3.7%) in the CP and sham CP groups, respectively (P = 0.70). The grades of laryngoscopic view and the Intubation Difficulty Scale score were also comparable. Median intubation time was slightly longer in the CP group than in the sham CP group (11.3 and 10.4 s, respectively, P = 0.001). Conclusions:CP applied by trained personnel does not increase the rate of failed intubation. Hence CP should not be avoided for fear of increasing the difficulty of intubation when its use is indicated.

Predictive value of S-100β protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis

Objectives To determine the ability and accuracy of the S-100β protein in predicting prognosis after a moderate or severe traumatic brain injury. Design Systematic review and meta-analysis of randomised controlled trials and observational studies. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, BIOSIS (from their inception to April 2012), conference abstracts, bibliographies of eligible articles, and relevant narrative reviews. Study selection Two reviewers independently reviewed citations and selected eligible studies, defined as cohort studies or randomised control trials including patients with moderate or severe traumatic brain injury and evaluating the prognostic value of S-100β protein. Outcomes evaluated were mortality, score on the Glasgow outcome scale, or brain death. Data extraction Two independent reviewers extracted data using a standardised form and evaluated the methodological quality of included studies. Pooled results were presented with geometric means ratios and analysed with random effect models. Prespecified sensitivity analyses were performed to explain heterogeneity. Results The search strategy yielded 9228 citations. Two randomised controlled trials and 39 cohort studies were considered eligible (1862 patients). Most studies (n=23) considered Glasgow outcome score ≤3 as an unfavourable outcome. All studies reported at least one measurement of S-100β within 24 hours after traumatic brain injury. There was a significant positive association between S-100β protein concentrations and mortality (12 studies: geometric mean ratio 2.55, 95% confidence interval 2.02 to 3.21, I2=56%) and score ≤3 (18 studies: 2.62, 2.01 to 3.42, I2=79%). Sensitivity analysis based on sampling time, sampling type, blinding of outcome assessors, and timing of outcome assessment yielded similar results. Thresholds for serum S-100β protein values with 100% specificity ranged from 1.38 to 10.50 µg/L for mortality (six studies) and from 2.16 to 14.00 µg/L for unfavourable neurological prognosis as defined by the Glasgow outcome score. Conclusions After moderate or severe traumatic brain injury, serum S-100β protein concentrations are significantly associated with unfavourable prognosis in the short, mid, or long term. Optimal thresholds for discrimination remain unclear. Measuring the S-100β protein could be useful in evaluating the severity of traumatic brain injury and in the determination of long term prognosis in patients with moderate and severe injury.

Evaluating the validity of multiple imputation for missing physiological data in the national trauma data bank

Background: The National Trauma Data Bank (NTDB) is plagued by the problem of missing physiological data. The Glasgow Coma Scale score, Respiratory Rate and Systolic Blood Pressure are an essential part of risk adjustment strategies for trauma system evaluation and clinical research. Missing data on these variables may compromise the feasibility and the validity of trauma group comparisons. Aims: To evaluate the validity of Multiple Imputation (MI) for completing missing physiological data in the National Trauma Data Bank (NTDB), by assessing the impact of MI on 1) frequency distributions, 2) associations with mortality, and 3) risk adjustment. Methods: Analyses were based on 170,956 NTDB observations with complete physiological data (observed data set). Missing physiological data were artificially imposed on this data set and then imputed using MI (MI data set). To assess the impact of MI on risk adjustment, 100 pairs of hospitals were randomly selected with replacement and compared using adjusted Odds Ratios (OR) of mortality. OR generated by the observed data set were then compared to those generated by the MI data set. Results: Frequency distributions and associations with mortality were preserved following MI. The median absolute difference between adjusted OR of mortality generated by the observed data set and by the MI data set was 3.6% (inter-quartile range: 2.4%-6.1%). Conclusions: This study suggests that, provided it is implemented with care, MI of missing physiological data in the NTDB leads to valid frequency distributions, preserves associations with mortality, and does not compromise risk adjustment in inter-hospital comparisons of mortality.

Efficacy and safety of dopamine agonists in traumatic brain injury: a systematic review of randomized controlled trials.

In the intensive care unit, dopamine agonists (DA) have been used in traumatic brain injury (TBI) patients to augment or accelerate cognitive recovery and rehabilitation. However, the efficacy and safety of DA in this population is not well established. We conducted a systematic review of randomized controlled trials (RCTs) examining the clinical efficacy and safety of DA in patients with TBI. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, comparing DA to either placebo, standard treatment, or another active comparator. There was no restriction for age, date, or language of publication. Sensitivity analyses were planned to evaluate the potential effect of timing of TBI, age, drugs, and year of publication on efficacy. Among the 790 citations identified, 20 RCTs evaluating methylphenidate, amantadine, and bromocriptine were eligible. Significant clinical heterogeneity was observed between and within studies, which precluded any pooling of data. Efficacy outcomes included mainly neuropsychological measures of cognitive functioning. A total of 76 different neuropsychological tests were used, but most of them (59%) only once. Only 5 studies systematically assessed safety. No trend could be drawn from the analysis of efficacy and safety. Important sources of bias in the studies were of major concern. Considering the absence of consensus regarding clinical outcome, the lack of safety assessment, and the high risk of bias in the included trials, more research is warranted before DA can be recommended in critically ill TBI patients.

Determination of neurologic prognosis and clinical decision making in adult patients with severe traumatic brain injury: a survey of Canadian intensivists, neurosurgeons, and neurologists.

Objectives:Accurate prognostic information in patients with severe traumatic brain injury remains limited, but mortality following the withdrawal of life-sustaining therapies is high and variable across centers. We designed a survey to understand attitudes of physicians caring for patients with severe traumatic brain injury toward the determination of prognosis and clinical decision making on the level of care. Design, Setting, and Participants:We conducted a cross-sectional study of intensivists, neurosurgeons, and neurologists that participate in the care of patients with severe traumatic brain injury at all Canadian level 1 and level 2 trauma centers. Intervention:None. Measurements:The main outcome measure was physicians’ perceptions of prognosis and recommendations on the level of care. Main Results:Our response rate was 64% (455/712). Most respondents (65%) reported that an accurate prediction of prognosis would be most helpful during the first 7 days. Most respondents (>80%) identified bedside monitoring, clinical exam, and imaging to be useful for evaluating prognosis, whereas fewer considered electrophysiology tests (<60%) and biomarkers (<15%). In a case-based scenario, approximately one-third of respondents agreed, one-third were neutral, and one-third disagreed that the patient prognosis would be unfavorable at one year. About 10% were comfortable recommending withdrawal of life-sustaining therapies. Conclusions:A significant variation in perceptions of neurologic prognosis and in clinical decision making on the level of care was found among Canadian intensivists, neurosurgeons, and neurologists. Improved understanding of the factors that can accurately predict prognosis for patients with traumatic brain injury is urgently needed.

A Comparison of a Single or Triple Injection Technique for Ultrasound-guided Infraclavicular Block: A Prospective Randomized Controlled Study

BACKGROUND: Good success rates have been reported with ultrasound-guided infraclavicular block using one or multiple injections of local anesthetic. We hypothesized that a separate injection of local anesthetics on each cord enhances the onset of complete sensory block. We designed this prospective randomized study to compare the rate of complete sensory block using one or three injections of local anesthetic. METHODS: Patients scheduled for hand, wrist, or elbow surgery were included in this study. All blocks were performed under ultrasound guidance. In Group S (single injection), 30 mL of mepivacaine 1.5% was injected posterior to the axillary artery. In Group T (triple injections), 10 mL of mepivacaine 1.5% was injected on the posterior, medial, and lateral aspects of the axillary artery. Sensory block was evaluated every 3 min up to 30 min. The primary end point was the rate of complete sensory block at 15 min. RESULTS: Forty-nine and 51 patients were randomized in Groups S and T, respectively. The rate of complete sensory block was comparable at 15 min (Group S: 84%, Group T: 78%, P = 0.61) and at each time interval up to 30 min. There was no statistically significant difference in the rate of complications between the two groups. CONCLUSIONS: The success rate and the onset of complete sensory block after ultrasound-guided infraclavicular block are not enhanced by a triple injection of local anesthetic compared with a single injection posterior to the axillary artery.

Effect of systemic steroids on post-tonsillectomy bleeding and reinterventions: systematic review and meta-analysis of randomised controlled trials

Objective To evaluate the risk of postoperative bleeding and reintervention with the use of systemic steroids in patients undergoing tonsillectomy. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, Cochrane Library, Scopus, Web of Science, Intute, Biosis, OpenSIGLE, National Technical Information Service, and Google Scholar were searched. References from reviews identified in the search and from included studies were scanned. Review methods Randomised controlled trials comparing the administration of systemic steroids during tonsillectomy with any other comparator were eligible. Primary outcome was postoperative bleeding. Secondary outcomes were the rate of admission for a bleeding episode, reintervention for a bleeding episode, blood transfusion, and mortality. Results Of 1387 citations identified, 29 randomised controlled trials (n=2674) met all eligibility criteria. Seven studies presented a low risk of bias, but none was specifically designed to systematically identify postoperative bleeding. Administration of systemic steroids did not significantly increase the incidence of post-tonsillectomy bleeding (29 studies, n=2674 patients, odds ratio 0.96 (95% confidence interval 0.66 to 1.40), I²=0%). We observed a significant increase in the incidence of operative reinterventions for bleeding episodes in patients who received systemic steroids (12, n=1178, 2.27 (1.03 to 4.99), I²=0%). No deaths were reported. Sensitivity analyses were consistent with the findings. Conclusions Although systemic steroids do not appear to increase bleeding events after tonsillectomy, their use is associated with a raised incidence of operative reinterventions for bleeding episodes, which may be related to increased severity of bleeding events. Systemic steroids should be used with caution, and the risks and benefits weighed, for the prevention of postoperative nausea and vomiting after tonsillectomy before further research is performed to clarify their condition of use.