Jan O Friedrich

University of Toronto, Toronto, Ontario, Canada

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Publications (72)303.78 Total impact

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    ABSTRACT: Enrollment of individual patients into more than one study has been poorly evaluated. The objective of this study was to describe the characteristics of patients, researchers and centers involved in coenrollment, studies precluding coenrollment, and the prevalence, patterns, predictors, and outcomes of coenrollment in a randomized clinical trial.
    Critical care medicine. 11/2014;
  • JAMA. 10/2014; 312(15):1588-1589.
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    Critical Care 10/2014; · 4.93 Impact Factor
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    ABSTRACT: IntroductionPatients with severe acute kidney injury (AKI) who are hospitalized at centres that do not provide renal replacement therapy (RRT) are frequently subjected to inter-hospital transfer for the provision of RRT. It is unclear whether such transfers are associated with worse patient outcomes as compared to the receipt of initial care in a centre that provides RRT. This study examined the relationship between inter-hospital transfer and 30-day mortality among critically ill patients with AKI who received RRT.Methods We conducted a retrospective cohort study of all critically ill patients who commenced RRT for AKI at two academic hospitals in Toronto, Canada. The exposure of interest was inter-hospital transfer for the administration of RRT. We evaluated the relationship between transfer status and 30-day mortality (primary outcome) and RRT dependence at 30 days following RRT initiation (secondary outcome) respectively, using multivariate logistic regression with adjustment for patient demographics, clinical factors, biochemical indices and severity of illness.ResultsOf 370 patients who underwent RRT for AKI, 82 (22.2%) were transferred for this purpose from another hospital. Compared to non-transferred patients who started RRT, transferred patients were younger (61¿±¿15 versus 65¿±¿15 years, P¿=¿0.03) and had a higher serum creatinine concentration at RRT initiation (474¿±¿295 versus 365¿±¿169 ¿mol/L, P¿=¿0.002). Inter-hospital transfer was not associated with mortality (adjusted OR 0.61, 95% CI 0.33 to 1.12) or RRT-dependence (adjusted OR 1.64, 95% CI 0.70 to 3.81) at 30 days.Conclusions Within the limitations of this observational study and the potential for residual confounding, inter-hospital transfer of critically ill patients with AKI was not associated with a higher risk of death or dialysis dependence 30 days after the initiation of acute RRT.
    Critical care (London, England) 09/2014; 18(5):513. · 4.72 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. SmartCare™ is a unique automated weaning system that measures selected respiratory variables, adapts ventilator output to individual patient needs by operationalizing predetermined algorithms and automatically conducts spontaneous breathing trials (SBTs) when predetermined thresholds are met.
    Cochrane database of systematic reviews (Online) 09/2014; 9:CD008638. · 5.70 Impact Factor
  • Critical care medicine. 08/2014; 42(8):e605-e606.
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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; · 7.13 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

Publication Stats

1k Citations
303.78 Total Impact Points

Institutions

  • 2005–2014
    • University of Toronto
      • • Department of Medicine
      • • Division of Critical Care Medicine
      • • Leslie L. Dan Faculty of Pharmacy
      Toronto, Ontario, Canada
  • 2005–2013
    • Trillium Health Centre
      Mississauga, Ontario, Canada
  • 2009–2012
    • Sunnybrook Health Sciences Centre
      • • Division of Nephrology
      • • Department of Critical Care Medicine
      Toronto, Ontario, Canada
  • 2005–2012
    • St. Michael's Hospital
      Toronto, Ontario, Canada