John Marshall

University of Toronto, Toronto, Ontario, Canada

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Publications (25)213.93 Total impact

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    ABSTRACT: ABSTRACT PURPOSE: Although secondary infections are recognized as a cause of morbidity and mortality in seasonal influenza, their frequency, characteristics and associated clinical outcomes in Influenza A (H1N1)-related critical illness are unknown. METHODS: In a prospective cohort of adult patients admitted to Canadian Intensive Care Units (ICUs) with H1N1 infection, the frequency and associated clinical outcomes of prevalent (culture taken within 72 hours of ICU admission) and ICU-acquired (culture taken after 72 hours from ICU admission) positive bacterial cultures were determined. RESULTS: Among 681 patients the mean age was 47.9 years (standard deviation [SD] 15.1), APACHE II was 21.0 (9.9) and 573 (84.0%) were invasively mechanical ventilated (MV). Positive cultures were obtained in 259 (38.0 %): 77 (29.7%) prevalent; 115 (44.4%) ICU-acquired; 40 (15.4%) had both; culture date was unavailable in 27 (10.4%). The most common bacterial organisms isolated were coagulase negative staphylococci, Staphylococcus aureus, Pseudomonas sp. and Streptococcus pneumoniae. Antibiotics were prescribed in 661 (97.1%) with 3.8 (1.9) prescriptions per patient. Patients with any positive culture had longer days of MV [mean(SD); 15.2 (10.7) vs. 10.7 (9.0), p< 0.0001], ICU stay [median(IQR);18.2 (12.5) vs. 10.8 (9.0) days, p< 0.0001], hospitalization [median(IQR); 30.7 (20.7) vs. 19.2 (17.4) days, p< 0.0001] and a trend towards increased hospital mortality (25.1% vs. 19.9%, p = 0.15). Patients with ICU-acquired positive cultures had worse outcomes compared to those with positive prevalent cultures or who were culture negative. CONCLUSION: Culture-based evidence of secondary infections commonly complicates Influenza A(H1N1)-related critical illness and is associated with worse clinical outcomes despite nearly ubiquitous antibiotic administration.
    Chest 02/2013; · 5.85 Impact Factor
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    ABSTRACT: INTRODUCTION: Research on coenrolment practices and its impact are limited in the ICU setting. The objectives of this study were; 1) to describe patterns and predictors of coenrolment of patients in a thromboprophylaxis trial, and 2) to examine the consequences of coenrolment on clinical and trial outcomes. METHODS: In an observational analysis of an international thromboprophylaxis trial in 67 ICUs, we examined the coenrolment of critically ill medical-surgical patients into more than one study, and examined the clinical and trial outcomes among coenrolled and non-coenrolled patients. RESULTS: Among 3746 patients enrolled in the Prophylaxis for ThromboEmbolism in Critical Care Trial, 713 (19.0%) were coenrolled in at least one other study (53.6% in a randomized trial, 37.0% in an observational study, and 9.4% in both). Six factors independently associated with coenrolment (all p<0.001) were illness severity (odds ratio [OR] 1.35, 95% confidence interval [CI] 1.19-1.53 for each 10 point APACHE II score increase), substitute decision-makers providing consent, rather than patients (OR 3.31, 2.03-5.41), experience of persons inviting consent (OR 2.67, 1.74-4.11 for persons with >10 years experience compared to persons with none), center size (all ORs >10 for ICUs with >15 beds), affiliation with trials groups (OR 5.59, 3.49-8.95), and main trial rather than pilot phase (all ORs >8 for recruitment year beyond the pilot). Coenrolment did not influence clinical or trial outcomes or risk of adverse events. CONCLUSIONS: Coenrolment was strongly associated with features of the patients, research personnel, setting and study. Coenrolment had no impact on trial results, and appeared safe, acceptable and feasible. Transparent reporting, scholarly discourse, ethical analysis, and further research are needed on the complex topic of coenrolment during critical illness.
    Critical care (London, England) 01/2013; 17(1):R1. · 4.72 Impact Factor
  • Journal of critical care 12/2012; 27(6):735-736. · 2.13 Impact Factor
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    ABSTRACT: To assess shock reversal and required fluid volumes in patients with septic shock. Prospective before and after study comparing three different treatment periods. Fifty-bed single-center surgical intensive care unit. Consecutive patients with severe sepsis. Fluid therapy directed at preset hemodynamic goals with hydroxyethyl starch (predominantly 6% hydroxyethyl starch 130/0.4) in the first period, 4% gelatin in the second period, and only crystalloids in the third period. Main outcome was time to shock reversal (serum lactate <2.2 mmol/L and discontinuation of vasopressor use). Hemodynamic goals were mean arterial pressure >70 mm Hg; ScvO2 <70%; central venous pressure >8 mm Hg. Safety outcomes were acute kidney injury defined by Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and new need for renal replacement therapy. Hemodynamic measures, serum lactate, and creatinine were comparable at baseline in all study periods (hydroxyethyl starch n = 360, gelatin n = 352, only crystalloids n = 334). Severity scores, hospital length of stay, and intensive care unit or hospital mortality did not differ significantly among groups. All groups showed similar time to shock reversal. More fluid was needed over the first 4 days in the crystalloid group (fluid ratios 1.4:1 [crystalloids to hydroxyethyl starch] and 1.1:1 [crystalloids to gelatin]). After day 5, fluid balance was more negative in the crystalloid group. Hydroxyethyl starch and gelatin were independent risk factors for acute kidney injury (odds ratio, 95% confidence interval 2.55, 1.76-3.69 and 1.85, 1.31-2.62, respectively). Patients receiving synthetic colloids received significantly more allogeneic blood products. Shock reversal was achieved equally fast with synthetic colloids or crystalloids. Use of colloids resulted in only marginally lower required volumes of resuscitation fluid. Both low molecular weight hydroxyethyl starch and gelatin may impair renal function.
    Critical care medicine 09/2012; 40(9):2543-51. · 6.37 Impact Factor
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    ABSTRACT: BACKGROUND:: Septic shock is a highly inflammatory and procoagulant state associated with significant mortality. In a single randomized controlled trial, recombinant human activated protein C (drotrecogin alfa) reduced mortality in patients with severe sepsis at high risk of death. Further clinical trials, including a recently completed trial in patients with septic shock, failed to reproduce these results. OBJECTIVE:: To evaluate the effectiveness of recombinant human activated protein C on mortality in a cohort of patients with septic shock and to explore possible reasons for inconsistent results in previous studies. DESIGN:: Retrospective, 2:1 propensity-matched, multicenter cohort study. SETTING:: Twenty-nine academic and community intensive care units in three countries. PATIENTS:: Seven thousand three hundred ninety-two adult patients diagnosed with septic shock, of which 349 received recombinant human activated protein C within 48 hrs of intensive care unit admission between 1997 and 2007. MEASUREMENTS AND MAIN RESULTS:: Our primary outcomes were mortality over 30 days and mortality stratified by Acute Physiology and Chronic Health Evaluation II quartile. Using a propensity-matched Cox proportional hazard model, we observed a 6.1% absolute reduction in 30-day mortality associated with the use of recombinant human activated protein C (108/311 [34.7%] vs. 254/622 [40.8%], hazard ratio 0.72, 95% confidence interval 0.52-1.00, p = .05) and noted consistent reductions in mortality among Acute Physiology and Chronic Health Evaluation II quartiles. A time to event analysis showed that the time to appropriate antimicrobials after documented hypotension decreased for each year of study (p = .003), a finding that was congruent with a decrease in annual mortality over the study period (odds ratio 0.96 per year [95% confidence interval 0.93-0.99], p = .003). CONCLUSIONS:: In this retrospective, propensity-matched, multicenter cohort study of patients with septic shock, early use of recombinant human activated protein C was associated with reduced mortality. Improvements in general quality of care such as speed of antimicrobial delivery leading to decreasing mortality of patients with septic shock may have contributed to the null results of the recently completed trial of recombinant human activated protein C in patients with septic shock.
    Critical care medicine 08/2012; 40(11):2974-2981. · 6.37 Impact Factor
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    ABSTRACT: Severe sepsis and septic shock are the most common reasons for admission to an intensive care unit; and the risk of death is substantial, estimated at approximately 40%. Evidence suggests that early resuscitation strategies that include the use of resuscitation fluids, antibiotics, blood, and inotropes reduce death. Although fluid resuscitation is an immediate life-saving intervention, a fundamental question that remains unanswered is whether the type of resuscitation fluid impacts survival when it is initiated very early in the course of septic shock. A randomized controlled trial published in 2008 confirmed that hydroxyethyl starch fluids cause acute renal failure defined by the requirement for renal replacement therapy. In contrast, a subgroup analysis from a randomized controlled trial suggests that 4% albumin fluid may reduce death from severe sepsis; however, these findings require confirmation in a large randomized trial. Our team is planning a pragmatic early septic shock fluid resuscitation trial that will compare the effectiveness of 5% albumin vs normal saline on 90-day mortality (PRECISE). In this article, we summarize the scientific rationale and inherent challenges associated with the conduct of PRECISE, the background work and planning elements that have been undertaken, and the PRECISE RCT protocol with rationale and justifications provided for the chosen population, the interventions, and the outcome measures.
    Transfusion medicine reviews 01/2012; 26(4):333-341. · 3.61 Impact Factor
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    ABSTRACT: Randomized, controlled trials of fluid resuscitation in early septic shock face many logistic challenges. We describe the Fluid Resuscitation with 5% albumin versus Normal Saline in Early Septic Shock (PRECISE) pilot trial study design and report feasibility of patient recruitment. Six Canadian academic centers enrolled adult patients with early suspected septic shock from the emergency department and intensive care unit department. Consent was deferred. Using concealed allocation, participants were randomized to either 5% albumin or 0.9% sodium chloride. Blinded fluid resuscitation started immediately and continued for 7 days in the intensive care unit. Target recruitment was established a priori at 2 patients per site per month. Fifty-one patients were enrolled; 50 patients received study fluid. We recruited a median of 2.5 patients (interquartile range [IQR], 1.5-3.0) per site per month into the trial. Median age and Acute Physiology and Chronic Health Evaluation II scores were 64.5 (IQR, 55.0-78.0) and 25.0 (IQR, 20.0-29.0), respectively. Most patients (n = 37 [74.0%]) were enrolled from the emergency department for a median of 1.6 hours (IQR, 0.8-3.5 hours) from their first hypotensive event and received a median of 2.4 L (IQR, 1.5-3.0 L) of resuscitation fluid before inclusion. Consent was deferred for 44 patients (89.8%). Patient recruitment into the PRECISE pilot trial met our prespecified feasibility targets, and the PRECISE team is planning the larger trial.
    Journal of critical care 12/2011; 27(3):317.e1-6. · 2.13 Impact Factor
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    ABSTRACT: Pandemic H1N1 influenza is projected to be unprecedented in its scope, causing acute critical illness among thousands of young otherwise healthy adults, who will need advanced life support. Rigorous, relevant, timely, and ethical clinical and health services research is crucial to improve their care and outcomes. Studies designed and conducted during a pandemic should be held to the same high methodologic and implementation standards as during other times. However, unique challenges arise with the need to conduct investigations as efficiently as possible, focused on the optimal outcome for the individual patient, while balancing the need for maximal societal benefit. We believe that clinical critical care research during a pandemic must be approached differently from research undertaken under nonemergent circumstances. We propose recommendations to clinical investigators and research ethics committees regarding clinical and health services research on pandemic-related critical illness. We also propose strategies such as expedited and centralized research ethics committee reviews and alternate consent models.
    Critical care medicine 12/2009; 38(4 Suppl):e138-42. · 6.37 Impact Factor
  • John Marshall, Konrad Reinhart
    Critical care medicine 12/2009; 37(12):3193. · 6.37 Impact Factor
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    ABSTRACT: Infection is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. However, relatively little information is available about the global epidemiology of such infections. To provide an up-to-date, international picture of the extent and patterns of infection in ICUs. The Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day, prospective, point prevalence study with follow-up conducted on May 8, 2007. Demographic, physiological, bacteriological, therapeutic, and outcome data were collected for 14,414 patients in 1265 participating ICUs from 75 countries on the study day. Analyses focused on the data from the 13,796 adult (>18 years) patients. On the day of the study, 7087 of 13,796 patients (51%) were considered infected; 9084 (71%) were receiving antibiotics. The infection was of respiratory origin in 4503 (64%), and microbiological culture results were positive in 4947 (70%) of the infected patients; 62% of the positive isolates were gram-negative organisms, 47% were gram-positive, and 19% were fungi. Patients who had longer ICU stays prior to the study day had higher rates of infection, especially infections due to resistant staphylococci, Acinetobacter, Pseudomonas species, and Candida species. The ICU mortality rate of infected patients was more than twice that of noninfected patients (25% [1688/6659] vs 11% [ 682/6352], respectively; P < .001), as was the hospital mortality rate (33% [2201/6659] vs 15% [ 942/6352], respectively; P < .001) (adjusted odds ratio for risk of hospital mortality, 1.51; 95% confidence interval, 1.36-1.68; P < .001). Infections are common in patients in contemporary ICUs, and risk of infection increases with duration of ICU stay. In this large cohort, infection was independently associated with an increased risk of hospital death.
    JAMA The Journal of the American Medical Association 12/2009; 302(21):2323-9. · 29.98 Impact Factor
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    ABSTRACT: Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America. To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection. 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. 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. 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). 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.
    JAMA The Journal of the American Medical Association 10/2009; 302(17):1872-9. · 29.98 Impact Factor
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    European Journal of Intensive Care Medicine 08/2009; 35(10):1655-8. · 5.17 Impact Factor
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    Intensive Care Medicine 02/2009; · 5.26 Impact Factor
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    ABSTRACT: To describe the incidence and outcomes associated with early acute kidney injury (AKI) in septic shock and explore the association between duration from hypotension onset to effective antimicrobial therapy and AKI. Retrospective cohort study. A total of 4,532 adult patients with septic shock from 1989 to 2005. Intensive care units of 22 academic and community hospitals in Canada, the United States and Saudi Arabia. In total, 64.4% of patients with septic shock developed early AKI (i.e., within 24 h after onset of hypotension). By RIFLE criteria, 16.3% had risk, 29.4% had injury and 18.7% had failure. AKI patients were older, more likely female, with more co-morbid disease and greater severity of illness. Of 3,373 patients (74.4%) with hypotension prior to receiving effective antimicrobial therapy, the median (IQR) time from hypotension onset to antimicrobial therapy was 5.5 h (2.0-13.3). Patients with AKI were more likely to have longer delays to receiving antimicrobial therapy compared to those with no AKI [6.0 (2.3-15.3) h for AKI vs. 4.3 (1.5-10.8) h for no AKI, P < 0.0001). A longer duration to antimicrobial therapy was also associated an increase in odds of AKI [odds ratio (OR) 1.14, 95% CI 1.10-1.20, P < 0.001, per hour (log-transformed) delay]. AKI was associated with significantly higher odds of death in both ICU (OR 1.73, 95% CI 1.60-1.9, P < 0.0001) and hospital (OR 1.62, 95% CI, 1.5-1.7, P < 0.0001). By Cox proportional hazards analysis, including propensity score-adjustment, each RIFLE category was independently associated with a greater hazard ratio for death (risk 1.31; injury 1.45; failure 1.56). Early AKI is common in septic shock. Delays to appropriate antimicrobial therapy may contribute to significant increases in the incidence of AKI. Survival was considerably lower for septic shock associated with early AKI, with increasing severity of AKI, and with increasing delays to appropriate antimicrobial therapy.
    European Journal of Intensive Care Medicine 01/2009; 35(5):871-81. · 5.17 Impact Factor
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    ABSTRACT: Severe sepsis and acute lung injury are challenging diagnoses as they relate to designing and reporting of clinical trials. The limited success in bringing forward new therapies in these areas is likely proof of that premise. The ability to use preclinical and phase I and II trial data to predict which patients and which dosing regimens are more likely to benefit is perhaps the greatest challenge. Animal models continue to be refined in attempts to more accurately reproduce human sepsis and acute lung injury. Oncology research should serve as a model for optimizing the integration of pharmacodynamics and pharmacogenetics into trial design. The European Organization for Research and Treatment of Cancer provides a valuable template for nonfunded multicenter clinical trial success. The marked heterogeneity of the patient population and small signal (tested therapy)-to-noise (comorbidities) ratio makes identification of treatment effect difficult. Dedicated investigators still enroll ineligible patients who are included in intent to treat analysis. High enrolling centers create less problems in an adequate test of a new therapy. Much has been learned from negative trials as to value of post hoc subgroup and interim analyses. Debate continues on fair and appropriate end point of trials. Extrapolation of adult positive trial results to children is problematic. Conflict of interest issues which rested dormantly for years are now at the forefront of discussion, and journal editorial board responsibility in this area is being recognized. Protocols may also help reduce heterogeneity of treatment across centers in clinical trials. This article reviews many of the problems encountered in clinical trial design and reporting and offers a perspective on dealing with them to the betterment of a clinical trial.
    Journal of critical care 01/2009; 23(4):493-9. · 2.13 Impact Factor
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    ABSTRACT: Despite practice guidelines promoting delirium assessment in intensive care, few data exist regarding current delirium assessment practices among nurses and how these practices compare with those for sedation assessment. To identify current practices and perceptions of intensive care nurses regarding delirium assessment and to compare practices for assessing delirium with practices for assessing sedation. A paper/Web-based survey was administered to 601 staff nurses working in 16 intensive care units at 5 acute care hospitals with sedation guidelines specifying delirium assessment in the Boston, Massachusetts area. Overall, 331 nurses (55%) responded. Only 3% ranked delirium as the most important condition to evaluate, compared with altered level of consciousness (44%), presence of pain (23%), or improper placement of an invasive device (21%). Delirium assessment was less common than sedation assessment (47% vs 98%, P < .001) and was more common among nurses who worked in medical intensive care units (55% vs 40%, P = .03) and at academic centers (53% vs 13%, P < .001). Preferred methods for assessing delirium included assessing ability to follow commands (78%), checking for agitation-related events (71%), the Confusion Assessment Method for the Intensive Care Unit (36%), the Intensive Care Delirium Screening Checklist (11%), and psychiatric consultation (9%). Barriers to assessment included intubation (38%), complexity of the tool for assessing delirium (34%), and sedation level (13%). Practice and perceptions of delirium assessment vary widely among critical care nurses despite the presence of institutional sedation guidelines that promote delirium assessment.
    American Journal of Critical Care 11/2008; 17(6):555-65; quiz 566. · 1.41 Impact Factor
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    ABSTRACT: Use of low-molecular-weight heparins is avoided in patients with renal insufficiency because of concerns about an excessive anticoagulant effect and increased bleeding risk. To challenge this premise, we evaluated if deep vein thrombosis (DVT) prophylaxis with dalteparin sodium confers an excessive anticoagulant effect in critically ill patients with severe renal insufficiency. We conducted a multicenter, single-arm clinical trial of DVT prophylaxis with dalteparin sodium, 5000 IU once daily in critically ill patients with a creatinine clearance lower than 30 mL/min (to convert to milliliters per second, multiply by 0.0167). Bioaccumulation was defined by a trough anti-Xa level higher than 0.40 IU/mL, measured twice weekly. The pharmacodynamic properties of dalteparin were assessed by serial anti-Xa levels measured on days 3, 10, and 17. We enrolled 156 patients with a mean (SD) creatinine clearance of 18.9 (6.5) mL/min; 18 were excluded because they died or were discharged before testing (n = 3) or had prevalent DVT (n = 15). Of 138 patients included, the median (interquartile range [IQR]) duration of dalteparin exposure was 7 (4-12) days. In 120 patients who had at least 1 trough anti-Xa level (427 total measurements), no patient had bioaccumulation (0%; 95% confidence interval [CI]: 0%-3.0%); the median (IQR) trough anti-Xa level was undetectable (<0.10 IU/mL [<0.10 to <0.10 IU/mL]). Based on serial measurements, peak anti-Xa levels were 0.29 to 0.34 IU/mL and trough levels were lower than 0.06 IU/mL. Deep vein thrombosis occurred in 7 of 138 patients (5.1%; 95% CI, 2.5%-10.1%); major bleeding occurred in 10 patients (7.2%; 95% CI, 4.0%-12.8%), all with trough anti-Xa levels of 0.18 IU/mL or lower. In critically ill patients with severe renal insufficiency, DVT prophylaxis with dalteparin sodium, 5000 IU once daily, is not associated with an excessive anticoagulant effect due to drug bioaccumulation and is unlikely to contribute to bleeding. Identifier: NCT00138099.
    Archives of internal medicine 09/2008; 168(16):1805-12. · 11.46 Impact Factor
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    ABSTRACT: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation (1) indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Key recommendations, listed by category, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for postoperative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B), targeting a blood glucose < 150 mg/dL after initial stabilization (2C); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); and a recommendation against the use of recombinant activated protein C in children (1B). There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.
    Critical care medicine 02/2008; 36(1):296-327. · 6.37 Impact Factor
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    ABSTRACT: A multidisciplinary research program on levels of care was conducted in 15 adult intensive care units in North America, Europe, and Australia. The program addressed advance directives for cardiopulmonary resuscitation, provision of advanced life support, and clinicians' discomfort with evolving treatment plans. The results indicated that the factors that determined the establishment of directives for advance life support differed from the factors that informed a decision to limit or withdraw support after admission to an intensive care unit. In addition, clinicians' prognoses were imprecise and often an underestimation of the probability of short-term survival. Finally, some degree of discomfort was common in care providers in the intensive care unit, most often because they thought interventions were excessive and not compatible with an acceptable future quality of life. The provision of advanced life support mandates explicit decision making about how life-support measures should be used.
    American Journal of Critical Care 06/2006; 15(3):269-79. · 1.41 Impact Factor
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    ABSTRACT: To examine the incidence and predictors of clinician discomfort with life support plans for ICU patients. Prospective cohort in 13 medical-surgical ICUs in four countries. 657 mechanically ventilated adults expected to stay in ICU at least 72 h. Daily we documented the life support plan for mechanical ventilation, inotropes and dialysis, and clinician comfort with these plans. If uncomfortable, clinicians stated whether the plan was too technologically intense (the provision of too many life support modalities or the provision of any modality for too long) or not intense enough, and why. At least one clinician was uncomfortable at least once for 283 (43.1%) patients, primarily because plans were too technologically intense rather than not intense enough (93.9% vs. 6.1%). Predictors of discomfort because plans were too intense were: patient age, medical admission, APACHE II score, poor prior functional status, organ dysfunction, dialysis in ICU, plan to withhold dialysis, plan to withhold mechanical ventilation, first week in the ICU, clinician, and city. Clinician discomfort with life support perceived as too technologically intense is common, experienced mostly by nurses, variable across centers, and is more likely for older, severely ill medical patients, those with acute renal failure, and patients lacking plans to forgo reintubation and ventilation. Acknowledging the sources of discomfort could improve communication and decision making.
    Intensive Care Medicine 10/2004; 30(9):1783-90. · 5.26 Impact Factor

Publication Stats

3k Citations
213.93 Total Impact Points


  • 2003–2013
    • University of Toronto
      • Department of Surgery
      Toronto, Ontario, Canada
  • 2011
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 2009
    • Université Libre de Bruxelles
      • Intensive Care Unit
      Brussels, BRU, Belgium
    • Cooper University Hospital
      • Department of Medicine
      Camden, New Jersey, United States
  • 2008–2009
    • St. Michael's Hospital
      Toronto, Ontario, Canada
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2004–2009
    • McMaster University
      • • Department of Medicine
      • • Department of Clinical Epidemiology and Biostatistics
      Hamilton, Ontario, Canada
    • Dalhousie University
      Halifax, Nova Scotia, Canada