Biomedical subjects
Publications and source records attributed to John V Peter.
A 50-year-old man was transferred to the intensive care unit with high anion gap metabolic acidosis. Investigations suggested a diagnosis of pyroglutamic acidaemia. Factors contributing to the acidosis were medications (paracetamol and flucloxacillin), sepsis and renal failure. The acidosis resolved with supportive therapy and withdrawal of the drugs. It is important to recognise this treatable aetiology of metabolic acidosis.
OBJECTIVE: The status of oximes in human organophosphate poisoning is controversial. This analysis compares the outcomes of therapy with or without oximes. DESIGN: Quantitative analysis using meta-analytic techniques. METHODS: Controlled trials of oximes in human organophosphate poisoning were identified by search of MEDLINE and TOXLINE (1966 to May 2005) and review of published articles. MEASUREMENTS AND MAIN RESULTS: Of the 3,122 articles on organophosphate poisoning identified by electronic search, 116 related to oxime use in human organophosphate poisoning. Seven trials, including two randomized controlled trials, compared oximes with standard medical care. Varying dosage schedules of pralidoxime or obidoxime were used. The effects of oxime therapy on mortality rate, mechanical ventilation, incidence of intermediate syndrome, and need for intensive care therapy were analyzed and expressed as risk difference (positive values indicating oxime harm). The random effects estimator was reported because of underlying heterogeneity of treatment effects between study types. No statistically significant association of oxime therapy was demonstrated for either mortality (risk difference 0.09, 95% confidence interval -0.08 to 0.27), ventilatory requirements (risk difference 0.16, 95% confidence interval -0.07 to 0.38), or the incidence of intermediate syndrome (risk difference 0.16, 95% confidence interval -0.12 to 0.45), although point estimates of effect suggested harm. An increased need for intensive care therapy (risk difference 0.19, 95% confidence interval 0.01 to 0.36) was apparent with oxime therapy. CONCLUSIONS: Based on the current available data on human organophosphate poisoning, oxime was associated with either a null effect or possible harm. The lack of current prospective randomized controlled trials, with appropriate patient stratification, mandates ongoing assessment of the role of oximes in organophosphate poisoning.
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OBJECTIVE: To present a meta-analytic update on the effects of noninvasive ventilation (NIV) in the management of acute respiratory failure. DESIGN: Meta-analysis of randomized controlled clinical trials in acute respiratory failure comparing NIV with standard medical therapy. PATIENTS: Randomized controlled trials of NIV in acute respiratory failure were identified by search of i) MEDLINE (1966-2000), ii) published abstracts from scientific meetings, and iii) bibliographies of relevant articles. MEASUREMENTS AND MAIN RESULTS: Of the 15 randomized controlled trials that were identified (13 published and 2 in abstract form), 8 studies were on exacerbations of chronic obstructive pulmonary disease (COPD) and 7 on diverse disease processes in both COPD and non-COPD groups ("mixed-group"). Because of underlying heterogeneity of treatment effects, only the DerSimonian-Laird random effects estimator was used and reported. The effects of NIV vs. standard therapy on mortality and subsequent invasive mechanical ventilation (MV) was assessed as risk difference, and hospital length of stay as mean weighted difference (days). NIV was associated with reduction in mortality (8%, p = .03), reduced need for MV (19%, p = .001) and shortened hospital length of stay (2.74 days, p = .004). In the COPD cohort, significant reductions in mortality (13%, p = .001), need for MV (18%, p = .02), and hospital length of stay (5.66 days, p = .01) were observed in the group treated with NIV. In contrast, in the mixed-group, there was no demonstrable reduction in mortality (0%, p = .98). However, there was significant reduction in the need for MV (22%, p = .001). Publication bias was not evident on analysis. Treatment effect i) as mortality or need for mechanical ventilation was not modified by enrollment pH, PaCO2, nor age and ii) was not related (as log odds ratio) to underlying risk (control arm log odds). Cumulative meta-analysis did not demonstrate any substantial variation in the point estimates with the addition of the recently published studies. However a contraction in the confidence intervals was observed in the COPD subgroup. Complication rates were not significantly different in the standard medical therapy group and the NIV treated patients. CONCLUSION: Substantial reductions in mortality and the need for subsequent MV were associated with NIV in acute respiratory failure, especially in the COPD subgroup. Hospital length of stay was variably affected. Heterogeneity of treatment effects was observed.