François Lauzier

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.

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.

Fresh frozen plasma transfusion in critically ill patients.

Objectives:Although guidelines for fresh frozen plasma (FFP) use have been published, many transfusions are considered inappropriate. Current guidelines suggest few circumstances in which FFP transfusion to critically ill patients is warranted. The objectives of this study were to evaluate the consistency of Canadian guidelines for FFP administration to critically ill patients and to examine factors associated with inappropriate FFP transfusions. Design:Retrospective cohort study. Setting:15-bed medical surgical intensive care unit in a teaching hospital. Patients:254 consecutive adults admitted during 1 yr expected to stay in intensive care for more than 72 hrs. Intervention:None. Measurements and Main Results:Patient demographics, illness severity, life support, intensive care and hospital length of stay, and survival were prospectively collected. All FFP orders were identified from the hospital laboratory information system. For each order, coagulation parameters, planned invasive interventions, recent or current bleeding, and bleeding severity were retrospectively collected. Three observers independently adjudicated whether transfusions were consistent with guidelines, inconsistent but appropriate for the intensive care context, or inappropriate. Of 254 patients, 76 (29.9%) received FFP, accounting for 225 orders to transfuse 547 units. Of 225 orders, 73 (32.4%) were consistent with guidelines, 45 (20.0%) were inconsistent but appropriate, and 107 (47.6%) were inappropriate. Considering transfusions clustered within patients, chance-independent agreement on whether transfusions were inappropriate or not was high (phi 0.73, 0.64–0.81). Independent determinants of inappropriate FFP were the presence of less severe coagulopathy as indicated by lower international normalized ratios (p < .0001) and the absence of bleeding (p < .0001) of planned invasive procedure (p = .0001). Conclusions:Critically ill patients frequently receive inappropriate FFP transfusions. Many transfusions may be appropriate for the intensive care setting, although they are inconsistent with expert recommendations, highlighting that further studies are needed to assess the effectiveness and safety of FFP transfusion in critical illness.

Thrombocytopenia in Critically Ill Patients Receiving Thromboprophylaxis: Frequency, Risk Factors, and Outcomes

BACKGROUND Thrombocytopenia is the most common hemostatic disorder in critically ill patients. The objective of this study was to describe the incidence, risk factors, and outcomes of thrombocytopenia in patients admitted to medical-surgical ICUs. METHODS Three thousand seven hundred forty-six patients in 67 centers were enrolled in a randomized trial in which unfractionated heparin was compared with low-molecular-weight heparin (LMWH) for thromboprophylaxis. Patients who had baseline platelet counts < 75 × 10(9)/L or severe coagulopathy at screening were excluded. We analyzed the risk of developing mild (100-149 × 10(9)/L), moderate (50-99 × 10(9)/L), and severe (< 50 × 109/L) thrombocytopenia during an ICU stay. We also assessed independent and time-varying predictors of thrombocytopenia and the effect of thrombocytopenia on major bleeding, transfusions, and death. RESULTS The incidences of mild, moderate, and severe thrombocytopenia were 15.3%, 5.1%, and 1.6%, respectively. The predictors of each category of thrombocytopenia were APACHE (Acute Physiology and Chronic Health Evaluation) II score, use of inotropes or vasopressors, and renal replacement therapy. The risk of moderate thrombocytopenia was lower in patients who received LMWH thromboprophylaxis but higher in surgical patients and in patients who had liver disease. Each category of thrombocytopenia was associated with subsequent bleeding and transfusions. Moderate and severe thrombocytopenia were associated with increased ICU and hospital mortality. CONCLUSION A high severity of illness, prior surgery, use of inotropes or vasopressors, renal replacement therapy, and liver dysfunction are associated with a higher risk of thrombocytopenia developing in the ICU, whereas LMWH thromboprophylaxis is associated with a lower risk. Patients who develop thrombocytopenia in the ICU are more likely to bleed, receive transfusions, and die.

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.

Efficacy of a T-piece system and a continuous positive airway pressure system for apnea testing in the diagnosis of brain death

Objective:To prospectively compare three methods of apnea testing for the confirmation of brain death. Design:Prospective, randomized, crossover study. Setting:Intensive care unit of a tertiary care university hospital. Patients:Twenty adult patients requiring apnea testing for confirmation of brain death. Interventions:Ten minute apnea testing was repeated in random order for every patient with the three oxygenation systems: oxygen catheter inserted through the endotracheal tube (oxygen 6 L/min), T-piece system (oxygen 12 L/min), and continuous positive airway pressure (CPAP) system 10 cm H2O (oxygen 12 L/min). Measurements and Main Results:Arterial blood was drawn at 0, 2, 5, and 10 mins of each test. Compared with baseline, Paco2 increased by 30.6 ± 7.4, 30.0 ± 7.3 and 30.2 ± 7.5 mm Hg during the apnea period (p = .96), reaching 73.3 ± 8.3, 71.6 ± 11.1, and 72.7 ± 9.0 mm Hg at the end of the apnea test (p = .73) for the oxygen catheter, the T-piece, and the CPAP, respectively. Pao2 decreased less with the CPAP compared with the oxygen catheter or the T-piece (−22.4 ± 76, −99.1 ± 158, and −91.6 ± 133 mm Hg, respectively, p < .01). In two patients, apnea testing could not be completed with the oxygen catheter and the T-piece because of desaturation, although it could be completed with the CPAP. Conclusions:The T-piece and the CPAP systems are effective alternatives to the standard oxygen catheter technique for apnea testing. Oxygenation was best maintained with the CPAP system, which can be useful in some patients.

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.

The use of higher platelet: RBC transfusion ratio in the acute phase of trauma resuscitation: a systematic review.

Objective:With the recognition of early coagulopathy, trauma resuscitation has shifted toward liberal platelet transfusions. The overall benefit of this strategy remains controversial. Our objective was to compare the effects of a liberal use of platelet (higher platelet:RBC ratios) with a conservative approach (lower ratios) in trauma resuscitation. Data Sources:We systematically searched Medline, Embase, Web of Science, Biosis, Cochrane Central, and Scopus. Study Selection:Two independent reviewers selected randomized controlled trials and observational studies comparing two or more platelet:RBC ratios in trauma resuscitation. We excluded studies investigating the use of whole blood or hemostatic products. Data Extraction:Two independent reviewers extracted data and assessed the risk of bias. Primary outcomes were early (in ICU or within 30 d) and late (in hospital or after 30 d) mortality. Secondary outcomes were multiple organ failure, lung injury, and sepsis. Data Synthesis:From 6,123 citations, no randomized controlled trials were identified. We included seven observational studies (4,230 patients) addressing confounders through multivariable regression or propensity scores. Heterogeneity of studies precluded meta-analysis. Among the five studies including exclusively patients requiring massive transfusions, four observed a lower mortality with higher ratios. Two studies considering nonmassively bleeding patients observed no benefit of using higher ratios. Two studies evaluated the implementation of a massive transfusion protocol; only one study observed a decrease in mortality with higher ratios. Of the two studies at low risk of survival bias, one study observed a survival benefit. Three studies assessed secondary outcomes. One study observed an increase in multiple organ failure with higher ratios, whereas no study demonstrated an increased risk in lung injury or sepsis. Conclusions:There is insufficient evidence to strongly support the use of a precise platelet:RBC ratio for trauma resuscitation, especially in nonmassively bleeding patients. Randomized controlled trials evaluating both the safety and efficacy of liberal platelet transfusions are warranted.

Hemoglobin levels and transfusions in neurocritically ill patients: a systematic review of comparative studies

IntroductionAccumulating evidence suggests that, in critically ill patients, a lower hemoglobin transfusion threshold is safe. However, the optimal hemoglobin level and associated transfusion threshold remain unknown in neurocritically ill patients.MethodsWe conducted a systematic review of comparative studies (randomized and nonrandomized) to evaluate the effect of hemoglobin levels on mortality, neurologic function, intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, and multiple organ failure in adult and pediatric neurocritically ill patients. We searched MEDLINE, The Cochrane Central Register of Controlled Trials, Embase, Web of Knowledge, and Google Scholar. Studies focusing on any neurocritical care conditions were included. Data are presented by using odds ratios for dichotomous outcomes and mean differences for continuous outcomes.ResultsAmong 4,310 retrieved records, six studies met inclusion criteria (n = 537). Four studies were conducted in traumatic brain injury (TBI), one in subarachnoid hemorrhage (SAH), and one in a mixed population of neurocritically ill patients. The minimal hemoglobin levels or transfusion thresholds ranged from 7 to 10 g/dl in the lower-Hb groups and from 9.3 to 11.5 g/dl in the higher-Hb groups. Three studies had a low risk of bias, and three had a high risk of bias. No effect was observed on mortality, duration of mechanical ventilation, or multiple organ failure. In studies reporting on length of stay (n = 4), one reported a significant shorter ICU stay (mean, -11.4 days (95% confidence interval, -16.1 to -6.7)), and one, a shorter hospital stay (mean, -5.7 days (-10.3 to -1.1)) in the lower-Hb groups, whereas the other two found no significant association.ConclusionsWe found insufficient evidence to confirm or refute a difference in effect between lower- and higher-Hb groups in neurocritically ill patients. Considering the lack of evidence regarding long-term neurologic functional outcomes and the high risk of bias of half the studies, no recommendation can be made regarding which hemoglobin level to target and which associated transfusion strategy (restrictive or liberal) to favor in neurocritically ill patients.