Jan O Friedrich

Trillium Health Centre, Mississauga, Ontario, Canada

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Publications (66)287.01 Total impact

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    ABSTRACT: Mechanical ventilation in the prone position is used to improve oxygenation and to mitigate the harmful effects of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). We sought to determine the effect of prone positioning on mortality among patients with ARDS receiving protective lung ventilation.
    05/2014;
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    ABSTRACT: Controversies regarding the process and timing of the determination of death for controlled organ donation after circulatory death persist. This study assessed the feasibility of conducting a prospective, observational study of continuous monitoring of vital signs for 30 minutes after the clinical determination of death in five Canadian ICUs. Waveform data were analyzed. Prospective observational cohort study. One pediatric and four adult Canadian ICUs. One month of age or older, admitted to the ICU, and for whom a consensual decision to withdraw life-sustaining therapies had been made, with an anticipation of imminent death. None. Invasive arterial blood pressure, electrocardiogram, and oxygen saturation plethysmography activity were recorded and reviewed for 30 minutes after declaration of death. Feasibility was assessed (recruitment, consent rate, protocol compliance, and staff satisfaction). Of 188 subjects screened over 16 months, 41 subjects were enrolled (87% consent rate). Data collection was complete for 30 subjects (73% protocol compliance). In four subjects, arterial blood pressure resumed following cessation of activity. The longest period of cessation of arterial blood pressure before resumption was 89 seconds. The duration of resumed activity ranged from 1 to 172 seconds. No cases of sustained resumption of arterial blood pressure activity were recorded, and no instances of clinical autoresuscitation were reported. In nearly all patients (27 of 30), electrocardiogram activity continued after the disappearance of arterial blood pressure. This is the first observational study to prospectively collect waveform data for 30 minutes after the declaration of death. A future larger study may support initial data suggesting that circulatory function does not resume after more than 89 seconds of absence. Furthermore, persistence of cardiac electrical activity with the documented absence of circulation may not be relevant to declaration of death.
    Critical care medicine 05/2014; · 6.37 Impact Factor
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    ABSTRACT: Thrombocytopenia occurs in 20% to 45% of critically ill medical-surgical patients. The 4Ts heparin-induced thrombocytopenia (HIT) score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher reason[s] for thrombocytopenia) might reliably identify patients at low risk for HIT. Interobserver agreement on 4Ts scoring is uncertain in this setting. To evaluate whether a published clinical prediction rule (the "4Ts score") reliably rules out HIT in "low-risk" intensive care unit (ICU) patients as assessed by research coordinators (who prospectively scored) and 2 adjudicators (who scored retrospectively) during an international heparin thromboprophylaxis trial (PROTECT, NCT00182143). Of 3746 medical-surgical ICU patients in PROTECT, 794 met the enrollment criteria for this HIT substudy. Enrollment was predicated on one of the following occurring in ICU: platelets less than 50 × 10(9)/L, platelets decreased to 50% of ICU admission value (if admission value <100 × 10(9)/L), any venous thrombosis, or if HIT was otherwise clinically suspected. Independently, 4Ts scores were completed in real time by research coordinators blinded to study drug and laboratory HIT results, and retrospectively by 2 adjudicators blinded to study drug, laboratory HIT results, and research coordinators' scores; the adjudicators arrived at consensus in all cases. Of the 763 patients, 474 had a central or local laboratory HIT test performed and had 4Ts scoring by adjudicators; 432 were scored by trained research coordinators. Heparin-induced thrombocytopenia was defined by a centrally performed positive serotonin release assay (SRA). Of the 474 patients with central adjudication, 407 (85.9%) had a 4Ts score of 3 or lower, conferring a low pretest probability (PTP) of HIT; of these, 6 (1.5% [95% confidence interval, 0.7%-3.2%) had a positive SRA. Fifty-nine (12.4%) had a moderate PTP (4Ts score of 4-5); of these, 4 (6.8%) had a positive SRA. Eight patients had a high PTP (4Ts score of ≥6); of these, 1 (12.5%) had a positive SRA. Raw agreement between research coordinators and central adjudication on each domain of the 4Ts score and low, intermediate, and high PTP was good. However, chance-corrected agreement was variable between adjudicators (weighted κ values of 0.31-0.93) and between the adjudicator consensus and research coordinators (weighted κ values of 0.13 and 0.78). Post hoc review of the 6 SRA-positive cases with an adjudicated low PTP demonstrated that their scores would have been increased if the adjudicators had had additional information on heparin exposure prior to ICU admission. In general, the fourth domain of 4Ts (oTher causes of thrombocytopenia) generated the most disagreement. Real-time 4Ts scoring by research coordinators at the time of testing for HIT was not consistent with 4Ts scores obtained by central adjudicators. The results of this comprehensive HIT testing highlight the need for further research to improve the assessment of PTP scoring of HIT for critically ill patients.
    Journal of critical care 02/2014; · 2.13 Impact Factor
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    ABSTRACT: Automated systems use closed-loop control to enable ventilators to perform basic and advanced functions while supporting respiration. Selected automated systems can now not only measure selected respiratory variables and adapt ventilator output to individual patient needs by operationalizing predetermined algorithms but also automate the conduct of spontaneous breathing trials (SBTs). To summarize the evidence comparing automated weaning and SBT systems to non-automated mechanical ventilation strategies on time to mechanical ventilation discontinuation in adult postoperative patients. In secondary objectives we ascertained differences between automated weaning and SBT systems and non-automated mechanical ventilation discontinuation strategies on clinical outcomes (time to successful extubation, time to first SBT and first successful SBT, mortality, total duration of ventilation, intensive care unit (ICU) and hospital lengths of stay, use of non-invasive ventilation (NIV) following extubation, and adverse events). We searched CENTRAL (The Cochrane Library 2013, Issue 5); MEDLINE (OvidSP) (1966 to May 2013); EMBASE (OvidSP) (1988 to May 2013); CINAHL (EBSCOhost) (1982 to May 2013), Evidence Based Medicine Reviews and Ovid Health Star (1999 to May 2013), conference proceedings, trial registration websites, and contacted authors and content experts to identify potentially eligible trials. Randomized and quasi-randomized trials comparing automated weaning and SBT systems to non-automated mechanical ventilation discontinuation strategies in intubated adults in the postoperative setting. Two review authors independently assessed trial quality and abstracted data according to prespecified criteria. Sensitivity and subgroup analyses were planned to assess the impact of the type of (i) clinician primarily involved in implementing the automated weaning and SBT systems, (ii) intensive care unit (ICU), and (iii) non-automated discontinuation (control) strategy utilized on selected outcomes. We identified one randomized controlled trial of high quality, involving 300 patients , comparing SmartCare™ to a written protocol. In this trial, SmartCare™ had no effect on discontinuation time. While SmartCare™ significantly reduced the time to the first SBT (mean difference (MD) -0.34 days, 95% CI -0.60 to -0.08; P = 0.01) it did not reduce the time to the first successful SBT (MD -0.25 days, 95% CI -0.55 to 0.05; P = 0.10) and other clinically important outcomes. SmartCare™ did not demonstrate beneficial effects on most clinically important outcomes including time to successful extubation, total duration of mechanical ventilation, ICU and hospital lengths of stay, and the requirement for tracheostomy. Moreover, SmartCare™ did not favourably impact reintubation, mortality, self-extubation, and the proportion of patients undergoing protracted mechanical ventilation, with a small numbers of events in this single trial. There is a paucity of evidence from randomized controlled trials to support or refute use of automated weaning and SBT systems in discontinuing invasive mechanical ventilation in adult postoperative patients. In a single large trial of high methodologic quality, while the use of SmartCare™ to adjust ventilator settings and conduct SBTs shortened the time to undergoing the first SBT, it did not reduce the time to the first successful SBT or the rate of tracheostomy compared to a written protocol implemented by physicians. SmartCare™ did not demonstrate beneficial effects on clinically important outcomes including time to mechanical ventilation discontinuation, time to successful discontinuation, total duration of mechanical ventilation, and ICU and hospital lengths of stay. Additional well-designed, adequately powered randomized controlled trials are needed to clarify the role for SmartCare™ on important outcomes in patients who predominantly require short term ventilation and in specific postoperative patient populations.
    Cochrane database of systematic reviews (Online) 02/2014; 2:CD008639. · 5.70 Impact Factor
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    ABSTRACT: The choice between coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) for revascularisation in patients with diabetes and multivessel coronary artery disease, who account for 25% of revascularisation procedures, is much debated. We aimed to assess whether all-cause mortality differed between patients with diabetes who had CABG or PCI by doing a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing CABG with PCI in the modern stent era. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from Jan 1, 1980, to March 12, 2013, for studies reported in English. Eligible studies were those in which investigators enrolled adult patients with diabetes and multivessel coronary artery disease, randomised them to CABG (with arterial conduits in at least 80% of participants) or PCI (with stents in at least 80% of participants), and reported outcomes separately in patients with diabetes, with a minimum of 12 months of follow-up. We used random-effects models to calculate risk ratios (RR) and 95% CIs for pooled data. We assessed heterogeneity using I(2). The primary outcome was all-cause mortality in patients with diabetes who had CABG compared with those who had PCI at 5-year (or longest) follow-up. The initial search strategy identified 3414 citations, of which eight trials were eligible. These eight trials included 7468 participants, of whom 3612 had diabetes. Four of the RCTs used bare metal stents (BMS; ERACI II, ARTS, SoS, MASS II) and four used drug-eluting stents (DES; FREEDOM, SYNTAX, VA CARDS, CARDia). At mean or median 5-year (or longest) follow-up, individuals with diabetes allocated to CABG had lower all-cause mortality than did those allocated to PCI (RR 0·67, 95% CI 0·52-0·86; p=0·002; I(2)=25%; 3131 patients, eight trials). Treatment effects in individuals without diabetes showed no mortality benefit (1·03, 0·77-1·37; p=0·78; I(2)=46%; 3790 patients, five trials; pinteraction=0.03). We identified no differences in outcome whether PCI was done with BMS or DES. When present, we identified no clear causes of heterogeneity. In the modern era of stenting and optimum medical therapy, revascularisation of patients with diabetes and multivessel disease by CABG decreases long-term mortality by about a third compared with PCI using either BMS or DES. CABG should be strongly considered for these patients. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Canada Research Chairs programme.
    The lancet. Diabetes & endocrinology. 12/2013; 1(4):317-28.
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    Clarence Chant, Ann Leung, Jan O Friedrich
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    ABSTRACT: The aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials such as extended/continuous infusions in critically ill patients is associated with improved outcomes as compared to traditional dosing methods METHODS: We searched Medline, HealthStar, EMBASE, Cochrane Clinical Trial Registry, and CINAHL from inception to September 2013 without language restrictions for studies comparing the use of extended/continuous infusions to traditional dosing. Two authors independently selected studies, extracted data on methodology and outcomes, and performed quality assessment. Meta-analyses were performed using random-effects models. Of 1319 citations, 13 randomized controlled trials (RCTs) (n = 782 patients) and 13 cohort studies (n = 2117 patients) met the inclusion criteria. Compared to traditional non-pharmacodynamic-based dosing, RCTs of continuous/extended infusions significantly reduced clinical failure rates (relative risk (RR) 0.68, 95% confidence interval (CI) 0.49 to 0.94, P = 0.02) and intensive care unit length of stay (mean difference -1.5, 95% CI -2.8 to -0.2 days, P = 0.02), but not mortality (RR 0.87, 95% CI 0.64 to 1.19, P = 0.38). There was no significant between-trial heterogeneity for these analyses (I2 = 0%). Reduced mortality rates almost achieved statistical significance when the results of all included studies (RCTs and cohort studies) were pooled (RR 0.83, 95% CI 0.69 to 1.00, P = 0.054). Pooled results from small RCTs suggest reduced clinical failure rates and intensive care unit length-of-stay when using continuous/extended infusions of antibiotics in critically ill patients. Reduced mortality rates almost achieved statistical significance when the results of RCTs were combined with cohort studies. These results support the conduct of adequately powered RCTs to better define the utility of continuous/extended infusions in the era of antibiotic resistance.
    Critical care (London, England) 11/2013; 17(6):R279. · 4.72 Impact Factor
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    ABSTRACT: Among critically ill patients with acute kidney injury, the impact of renal replacement therapy modality on long-term kidney function is unknown. Compared with conventional intermittent hemodialysis, continuous renal replacement therapy may promote kidney recovery by conferring greater hemodynamic stability; yet continuous renal replacement therapy may not enhance patient survival and is resource intense. Our objective was to determine whether continuous renal replacement therapy was associated with a lower risk of chronic dialysis as compared with intermittent hemodialysis, among survivors of acute kidney injury. Retrospective cohort study. Linked population-wide administrative databases in Ontario, Canada. Critically ill adults who initiated dialysis for acute kidney injury between July 1996 and December 2009. In the primary analysis, we considered those who survived to at least 90 days after renal replacement therapy initiation. Initial receipt of continuous renal replacement therapy versus intermittent hemodialysis. Continuous renal replacement therapy recipients were matched 1:1 to intermittent hemodialysis recipients based on a history of chronic kidney disease, receipt of mechanical ventilation, and a propensity score for the likelihood of receiving continuous renal replacement therapy. Cox proportional hazards were used to evaluate the relationship between initial renal replacement therapy modality and the primary outcome of chronic dialysis, defined as the need for dialysis for a consecutive period of 90 days. We identified 2,315 continuous renal replacement therapy recipients of whom 2,004 (87%) were successfully matched to 2,004 intermittent hemodialysis recipients. Participants were followed over a median duration of 3 years. The risk of chronic dialysis was significantly lower among patients who initially received continuous renal replacement therapy versus intermittent hemodialysis (hazard ratio, 0.75; 95% CI, 0.65-0.87). This relation was more prominent among those with preexisting chronic kidney disease (p value for interaction term = 0.065) and heart failure (p value for interaction term = 0.035). Compared with intermittent hemodialysis, initiation of continuous renal replacement therapy in critically ill adults with acute kidney injury is associated with a lower likelihood of chronic dialysis.
    Critical care medicine 11/2013; · 6.37 Impact Factor
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    ABSTRACT: Treatment with inhaled nitric oxide improves oxygenation but not survival in mechanically ventilated patients with acute respiratory distress syndrome, but the effect may depend on the severity of hypoxemia. Our objective was to determine whether nitric oxide reduces hospital mortality in patients with severe acute respiratory distress syndrome (PaO2/FIO2 ≤ 100 mm Hg) but not in patients with mild-moderate acute respiratory distress syndrome (100 < PaO2/FIO2 ≤ 300 mm Hg) at the time of randomization. Data were collected from Medline, Embase, and Cochrane CENTRAL electronic databases (inception to May 2013); proceedings from five conferences (to May 2013); and trial registries (http://www.clinicaltrials.gov and http://www.controlled-trials.com). No language restrictions were applied. Two authors independently selected parallel-group randomized controlled trials comparing nitric oxide with control (placebo or no gas) in mechanically ventilated adults or postneonatal children with acute respiratory distress syndrome. Two authors independently extracted data from included trials. Trial investigators provided subgroup data. Meta-analyses used within-trial subgroups and random-effects models. Nine trials (n = 1,142 patients) met inclusion criteria. Overall methodological quality was good. Nitric oxide did not reduce mortality in patients with severe acute respiratory distress syndrome (risk ratio, 1.01 [95% CI, 0.78-1.32]; p = 0.93; n = 329, six trials) or mild-moderate acute respiratory distress syndrome (risk ratio, 1.12 [95% CI, 0.89-1.42]; p = 0.33; n = 740, seven trials). Risk ratios were similar between subgroups (interaction p = 0.53). There was no between-trial heterogeneity in any analysis (I = 0%). Varying the PaO2/FIO2 threshold between 70 and 200 mm Hg, in increments of 10 mm Hg, did not identify any threshold at which the nitric oxide-treated patients had lower mortality relative to controls. Nitric oxide does not reduce mortality in adults or children with acute respiratory distress syndrome, regardless of the degree of hypoxemia. Given the lack of related ongoing or recently completed randomized trials, new data addressing the effectiveness of nitric oxide in patients with acute respiratory distress syndrome and severe hypoxemia will not be available for the foreseeable future.
    Critical care medicine 10/2013; · 6.37 Impact Factor
  • European Journal of Intensive Care Medicine 10/2013; · 5.17 Impact Factor
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    Canadian respiratory journal: journal of the Canadian Thoracic Society 09/2013; · 1.29 Impact Factor
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    ABSTRACT: We systematically reviewed ICU-based knowledge translation studies to assess the impact of knowledge translation interventions on processes and outcomes of care. We searched electronic databases (to July, 2010) without language restrictions and hand-searched reference lists of relevant studies and reviews. Two reviewers independently identified randomized controlled trials and observational studies comparing any ICU-based knowledge translation intervention (e.g., protocols, guidelines, and audit and feedback) to management without a knowledge translation intervention. We focused on clinical topics that were addressed in greater than or equal to five studies. Pairs of reviewers abstracted data on the clinical topic, knowledge translation intervention(s), process of care measures, and patient outcomes. For each individual or combination of knowledge translation intervention(s) addressed in greater than or equal to three studies, we summarized each study using median risk ratio for dichotomous and standardized mean difference for continuous process measures. We used random-effects models. Anticipating a small number of randomized controlled trials, our primary meta-analyses included randomized controlled trials and observational studies. In separate sensitivity analyses, we excluded randomized controlled trials and collapsed protocols, guidelines, and bundles into one category of intervention. We conducted meta-analyses for clinical outcomes (ICU and hospital mortality, ventilator-associated pneumonia, duration of mechanical ventilation, and ICU length of stay) related to interventions that were associated with improvements in processes of care. From 11,742 publications, we included 119 investigations (seven randomized controlled trials, 112 observational studies) on nine clinical topics. Interventions that included protocols with or without education improved continuous process measures (seven observational studies and one randomized controlled trial; standardized mean difference [95% CI]: 0.26 [0.1, 0.42]; p = 0.001 and four observational studies and one randomized controlled trial; 0.83 [0.37, 1.29]; p = 0.0004, respectively). Heterogeneity among studies within topics ranged from low to extreme. The exclusion of randomized controlled trials did not change our results. Single-intervention and lower-quality studies had higher standardized mean differences compared to multiple-intervention and higher-quality studies (p = 0.013 and 0.016, respectively). There were no associated improvements in clinical outcomes. Knowledge translation interventions in the ICU that include protocols with or without education are associated with the greatest improvements in processes of critical care.
    Critical care medicine 08/2013; · 6.37 Impact Factor
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    ABSTRACT: 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 intensive care units (ICUs). 3746 patients in 67 centers were enrolled in a randomized trial in which unfractionated heparin was compared to low-molecular-weight heparin (LMWH) for thromboprophylaxis. Patients who had baseline platelet counts <75x109/L or severe coagulopathy at screening were excluded. We analyzed the risk of developing mild (100-149x109/L), moderate (50-99x109/L) and severe (<50x109/L) thrombocytopenia during ICU stay. We also assessed independent and time-varying predictors of thrombocytopenia and the effect of thrombocytopenia on major bleeding, transfusions, and death. The incidence of mild, moderate, and severe thrombocytopenia was 15.3%, 5.1% and 1.6%, respectively. Predictors of each category of thrombocytopenia were: APACHE 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. 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 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.
    Chest 06/2013; · 5.85 Impact Factor
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    ABSTRACT: High frequency oscillation is an alternative to conventional mechanical ventilation that is sometimes used to treat patients with acute respiratory distress syndrome, but effects on oxygenation, mortality and adverse clinical outcomes are uncertain. This review was originally published in 2004 and was updated in 2011. To determine clinical and physiological effects of high frequency oscillation (HFO) in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) compared to conventional ventilation. We electronically searched CENTRAL (Ovid), MEDLINE (Ovid), EMBASE (Ovid), and ISI (from inception to March 2011). The original search was performed in 2002. We manually searched reference lists from included studies and review articles; searched conference proceedings of the American Thoracic Society (1994 to 2010), Society of Critical Care Medicine (1994 to 2010), European Society of Intensive Care Medicine (1994 to 2010), and American College of Chest Physicians (1994 to 2010); contacted clinical experts in the field; and searched for unpublished and ongoing trials in clinicaltrials.gov and controlled-trials.com. Randomized controlled clinical trials comparing treatment using HFO with conventional mechanical ventilation for children and adults diagnosed with ALI or ARDS. Three authors independently extracted data on clinical, physiological, and safety outcomes according to a predefined protocol. We contacted investigators of all included studies to clarify methods and obtain additional data. We used random-effects models in the analyses. Eight RCTs (n = 419) were included; almost all patients had ARDS. The risk of bias was low in six studies and unclear in two studies. The quality of evidence for hospital and six-month mortality was moderate and low, respectively. The ratio of partial pressure of oxygen to inspired fraction of oxygen at 24, 48, and 72 hours was 16% to 24% higher in patients receiving HFO. There were no significant differences in oxygenation index because mean airway pressure rose by 22% to 33% in patients receiving HFO (P < 0.01). In patients randomized to HFO, mortality was significantly reduced (RR 0.77, 95% CI 0.61 to 0.98; P = 0.03; 6 trials, 365 patients, 160 deaths) and treatment failure (refractory hypoxaemia, hypercapnoea, hypotension, or barotrauma) was less likely (RR 0.67, 95% CI 0.46 to 0.99; P = 0.04; 5 trials, 337 patients, 73 events). Other risks, including adverse events, were similar. We found substantial between-trial statistical heterogeneity for physiological (I = 21% to 95%) but not clinical (I = 0%) outcomes. Pooled results were based on few events for most clinical outcomes. The findings of this systematic review suggest that HFO was a promising treatment for ALI and ARDS prior to the uptake of current lung protective ventilation strategies. These findings may not be applicable with current conventional care, pending the results of large multi-centre trials currently underway.
    Cochrane database of systematic reviews (Online) 01/2013; 2:CD004085. · 5.70 Impact Factor
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    ABSTRACT: INTRODUCTION: Among critically ill patients with acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT), the effect of convective (via continuous venovenous hemofiltration [CVVH]) versus diffusive (via continuous venovenous hemodialysis [CVVHD]) solute clearance on clinical outcomes is unclear. Our objective was to evaluate the feasibility of comparing these two modes in a randomized trial. METHODS: This was a multicentre open-label parallel-group pilot randomized trial of CVVH versus CVVHD. Using concealed allocation, we randomized critically ill adults with AKI and hemodynamic instability to CVVH or CVVHD, with a prescribed small solute clearance of 35 mL/kg/hour in both arms. The primary outcome was trial feasibility, defined by randomization of >25% of eligible patients, delivery of >75% of the prescribed CRRT dose, and follow-up of >95% of patients to 60 days. A secondary analysis using a mixed-effects model examined the impact of therapy on illness severity, defined by sequential organ failure assessment (SOFA) score, over the first week. RESULTS: We randomized 78 patients (mean age 61.5 years; 39% women; 23% with chronic kidney disease; 82% with sepsis). Baseline SOFA scores (mean 15.9, SD 3.2) were similar between groups. We recruited 55% of eligible patients, delivered >80% of the prescribed dose in each arm, and achieved 100% follow-up. SOFA tended to decline more over the first week in CVVH recipients (-0.8, 95% CI -2.1, +0.5) driven by a reduction in vasopressor requirements. Mortality (54% CVVH; 55% CVVHD) and dialysis dependence in survivors (24% CVVH; 19% CVVHD) at 60 days were similar. CONCLUSIONS: Our results suggest that a large trial comparing CVVH to CVVHD would be feasible. There is a trend toward improved vasopressor requirements among CVVH-treated patients over the first week of treatment. Trial registration: ClinicalTrials.gov NCT00675818.
    Critical care (London, England) 10/2012; 16(5):R205. · 4.72 Impact Factor
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    ABSTRACT: INTRODUCTION: The objective of this systematic review and meta-analysis was to determine the effect of renal replacement therapy (RRT), delivered as hemofiltration vs. hemodialysis, on clinical outcomes in patients with acute kidney injury (AKI). METHODS: MEDLINE, EMBASE, and CENTRAL databases and conference abstracts were searched to June 2012 for parallel-group or crossover randomized and quasi-randomized controlled trials (RCTs) evaluating hemofiltration vs. hemodialysis in patients with AKI. Two authors independently selected studies and abstracted data on study quality and outcomes. Additional information was obtained from trial authors. We pooled data using random-effects models. RESULTS: Of 6657 citations, 19 RCTs (10 parallel-group and 9 crossover) met inclusion criteria. Sixteen trials used continuous RRT. Study quality was variable. The primary analysis included 3 parallel-group trials comparing similar doses of hemofiltration and hemodialysis; sensitivity analyses included trials comparing combined hemofiltration-hemodialysis or dissimilar doses. We found no effect of hemofiltration on mortality (risk ratio [RR] 0.96, 95% confidence interval [CI] 0.73-1.25, p=0.76; 3 trials, n=121 [primary analysis]; RR 1.10, 95%CI 0.88-1.38, p=0.38; 8 trials, n=540 [sensitivity analysis]) or other clinical outcomes (RRT dependence in survivors, vasopressor use, organ dysfunction) compared to hemodialysis. Hemofiltration appeared to shorten time to filter failure (mean difference [MD] -7 hours, 95%CI[-19,+5], p=0.24; 2 trials, n=50 [primary analysis]; MD -5 hours, 95%CI[-10, -1], p=0.01; 3 trials, n=113 [including combined hemofiltration-hemodialysis trials comparing similar doses]; MD -6 hours, 95% CI[-10, -1], p=0.02; 5 trials, n=383 [sensitivity analysis]). Data primarily from crossover RCTs suggested that hemofiltration increased clearance of medium to larger molecules, including inflammatory cytokines, compared to hemodialysis, although almost no studies measured changes in serum concentrations. Meta-analyses were based on very limited data. CONCLUSIONS: Data from small RCTs do not suggest beneficial clinical outcomes from hemofiltration, but confidence intervals were wide. Hemofiltration may increase clearance of medium to larger molecules. Larger trials are required to evaluate effects on clinical outcomes.
    Critical care (London, England) 08/2012; 16(4):R146. · 4.72 Impact Factor
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    ABSTRACT: PURPOSE: We undertook this study to characterize the epidemiology of acute kidney injury (AKI) in Canadian critical care units. We aimed to identify predictors of mortality for patients diagnosed with AKI. METHODS: We conducted a prospective cohort study of consecutive patients admitted to critical care units at five Canadian hospitals over a 30-day period. Each patient was followed until hospital discharge or for a maximum of 30 days. The serum creatinine criteria for the Acute Kidney Injury Network (AKIN-SCr) system were used to identify, classify, and characterize patients who developed AKI. We used multivariable logistic regression to predict 30-day mortality among patients with AKI. RESULTS: We identified 603 patients, 161 (26.7%) of whom developed AKI. Compared to patients without AKI, those with AKI were more likely to die (29.2% vs 8.6%, P < 0.001). The risk of death increased with increasing AKIN-SCr stage (P < 0.001). In all, 19 patients (11.8% of those with AKI) commenced dialysis a median of one day (interquartile range, one to two days) after AKI diagnosis. At AKI diagnosis, the blood urea nitrogen (BUN) level (adjusted odds ratio [OR] 1.68, 95% confidence interval [CI] 1.01 to 2.79/10 mmol·L(-1)) and serum bicarbonate (adjusted OR 0.88, 95% CI 0.81 to 0.95/1 mmol·L(-1)) were associated with 30-day mortality and predicted death with an area under the receiver-operating characteristic curve of 0.79 (95% CI 0.71 to 0.86). CONCLUSIONS: Acute kidney injury is a common complication of critical illness in Canada. The development of even the mildest stage of AKI is associated with a substantially higher risk of death. At AKI diagnosis, routine clinical data may be helpful for predicting adverse outcomes.
    Canadian Anaesthetists? Society Journal 07/2012; 59(10):934-942. · 2.31 Impact Factor
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    ABSTRACT: To examine the attitudes and preferences of surrogate decision makers (SDMs) regarding their involvement in the consent to research process for ICU patients. We presented 136 SDMs of critically ill patients in five ICUs with four hypothetical research scenarios: baseline interventional study of a placebo controlled RCT; study with higher risk of treatment complication; study comparing two accepted treatments; study with shorter enrolment window. For each we asked SDMs if they would want to be involved in the consent to research decision, and to rate the acceptability of their comfort with, and their sense of burden with their involvement. Participants were screened for symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale. For the baseline scenario, most SDMs wished to be involved in research decision making (90 %; 95 % CI 84-95 %); responses varied little across study permutations. The majority considered their involvement to be acceptable (85 %; 95 % CI 77-90 %), whereas, a small minority rated it as being unacceptable (2 %; 95 % CI 1-6 %). Many were comfortable with being involved (50 %; 95 % CI 41-59 %), but the number decreased when risk of harm was higher (34 %; 95 % CI 26-43 %) or enrolment window was shorter (41 %; 95 % CI 33-50 %). A majority (62 %) reported symptoms of anxiety and many (38 %) had symptoms of depression. Most of the interviewed SDMs wished to be involved in research decision making for critically ill and incapable loved ones. Variability existed, however, in their desire to be involved when decisions were time-sensitive or perceived risk was greater.
    European Journal of Intensive Care Medicine 07/2012; 38(10):1616-23. · 5.17 Impact Factor
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    ABSTRACT: Paper-based nomograms are reasonably effective for achieving glycemic control but have low adherence and are less adaptive than nurses' judgment. To compare efficacy (glucose control) and safety (hypoglycemia) achieved by use of a paper nomogram versus nurses' judgment. Prospective, randomized, open-label, crossover trial in an intensive care unit in postoperative patients with glucose concentrations greater than 8 mmol/L. Consenting nurses with at least 1 year of experience were randomized to use either their judgment or a validated paper-based nomogram for glucose control. After completion of 2 study shifts, the nurses used the alternative method for the next 2 study shifts. Glucose target level and safety and efficacy boundaries were the same for both methods. The primary end point was area under glucose time curve per hour. Thirty-four nurses contributed 95 shifts of data (44 nomogram-directed, 51 nurse-directed). Adherence to the nomogram was higher in the nomogram group than hypothetical adherence in the nurse-directed group for correct adjustments in insulin infusion (70% vs 37%; P < .001) and glucose checks (58% vs 43%; P = .008). The primary end point did not differ between the 2 groups (mean, 9.0 mmol/L; SD, 3.5 vs mean, 8.3 mmol/L; SD, 2.1; P = .08). Glucose variability, amount of time patients were hypoglycemic or hyperglycemic, and number of glucose checks performed were similar in the 2 groups. In an intensive care unit where nurses generally accepted the need for tight glucose control, nurse-directed control was as effective and as safe as nomogram-based control.
    American Journal of Critical Care 07/2012; 21(4):270-8. · 1.41 Impact Factor
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    ABSTRACT: The optimal timing for starting renal replacement therapy (RRT) in patients with acute kidney injury (AKI) is unknown. Defining current practice is necessary to design interventional trials. We describe the current Canadian practice regarding the timing of RRT initiation for AKI. An observational study of patients undergoing RRT for AKI was undertaken at 11 intensive care units (ICUs) across Canada. Data were captured on demographics, clinical and laboratory findings, indications for RRT, and timing of RRT initiation. Among 119 consecutive patients, the most common ICU admission diagnosis was sepsis/septic shock, occurring in 54%. At the time of RRT initiation, the median and interquartile range (IQR) serum creatinine level was 322 (221-432) μmol·L(-1). The mean (SD) values for other parameters were as follows: Sequential Organ Failure Assessment (SOFA) score 13.4 (4.1), pH 7.25 (0.15), potassium 4.6 (1.0) mmol·L(-1). Also, 64% fulfilled the serum creatinine-based criterion for Acute Kidney Injury Network (AKIN) stage 3. Severity of illness, measured using Acute Physiology and Chronic Health Evaluation (APACHE II) and SOFA scores, did not correlate with AKI severity as defined by the serum creatinine-based AKIN criteria. Median (IQR) time from hospital and ICU admission to the start of RRT was 2.0 (1.0-7.0) days and 1.0 (0-2.0) day, respectively. Patients admitted to an ICU who were started on RRT generally had advanced AKI, high-grade illness severity, and multiorgan dysfunction. Also, they were started on RRT shortly after hospital presentation. We describe the current state of practice in Canada regarding the initiation of RRT for AKI in critically ill patients, which can inform the designs of future interventional trials.
    Canadian Anaesthetists? Society Journal 06/2012; 59(9):861-70. · 2.31 Impact Factor
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    ABSTRACT: Acute kidney injury frequently arises within an acute care hospitalization. Outcomes among acute kidney injury survivors following hospital discharge are poorly documented. We conducted a population-based cohort study between 1996 and 2006 of all adult patients in Ontario with acute kidney injury who did not require in-hospital dialysis, and who survived free of dialysis ≥30 days after discharge. Those with acute kidney injury (n=41,327) were matched 1:1 to patients without acute kidney injury during their index hospitalization. Matching was by age (±1 year), sex, history of chronic kidney disease, receipt of mechanical ventilation during the index hospitalization, and a propensity score for developing acute kidney injury. The primary outcome was subsequent need for chronic dialysis. The secondary outcomes were all-cause mortality and rehospitalization. Mean age was 70 years, and median follow-up was 2 years (maximum 10 years). The incidence of chronic dialysis was 1.78 per 100 person-years among those with acute kidney injury and 0.74 per 100 person-years among unaffected controls (adjusted hazard ratio [HR]; 2.70, 95% confidence interval [CI], 2.42-3.00). Rates also were higher for all-cause mortality (15.34 vs 14.51 per-100 person-years; adjusted HR 1.10; 95% CI, 1.07-1.13) and rehospitalization (44.93 vs 37.18 per 100 person-years; adjusted HR 1.21; 95% CI, 1.18-1.24). Even when acute dialysis is not required, survivors of acute kidney injury remain at higher risk of receipt of chronic dialysis thereafter. The absolute risk of death was more than 8 times the rate of chronic dialysis.
    The American journal of medicine 04/2012; 125(6):585-93. · 5.30 Impact Factor

Publication Stats

1k Citations
287.01 Total Impact Points

Institutions

  • 2005–2013
    • Trillium Health Centre
      Mississauga, Ontario, Canada
  • 2005–2012
    • University of Toronto
      • • Department of Medicine
      • • Division of Critical Care Medicine
      • • Leslie L. Dan Faculty of Pharmacy
      Toronto, Ontario, Canada
    • St. Michael's Hospital
      Toronto, Ontario, Canada
  • 2009–2011
    • Sunnybrook Health Sciences Centre
      • Department of Critical Care Medicine
      Toronto, Ontario, Canada