John Victor Peter

Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis

Objective To systematically review the efficacy of steroids in the prevention of acute respiratory distress syndrome (ARDS) in critically ill adults, and treatment for established ARDS. Data sources Search of randomised controlled trials (1966-April 2007) of PubMed, Cochrane central register of controlled trials, Cochrane database of systematic reviews, American College of Physicians Journal Club, health technology assessment database, and database of abstracts of reviews of effects. Data extraction Two investigators independently assessed trials for inclusion and extracted data into standardised forms; differences were resolved by consensus. Data synthesis Steroid efficacy was assessed through a Bayesian hierarchical model for comparing the odds of developing ARDS and mortality (both expressed as odds ratio with 95% credible interval) and duration of ventilator free days, assessed as mean difference. Bayesian outcome probabilities were calculated as the probability that the odds ratio would be ≥1 or the probability that the mean difference would be ≥0. Nine randomised trials using variable dose and duration of steroids were identified. Preventive steroids (four studies) were associated with a trend to increase both the odds of patients developing ARDS (odds ratio 1.55, 95% credible interval 0.58 to 4.05; P(odds ratio ≥1)=86.6%), and the risk of mortality in those who subsequently developed ARDS (three studies, odds ratio 1.52, 95% credible interval 0.30 to 5.94; P(odds ratio ≥1)=72.8%). Steroid administration after onset of ARDS (five studies) was associated with a trend towards reduction in mortality (odds ratio 0.62, 95% credible interval 0.23 to 1.26; P(odds ratio ≥1)=6.8%). Steroid therapy increased the number of ventilator free days compared with controls (three studies, mean difference 4.05 days, 95% credible interval 0.22 to 8.71; P(mean difference ≥0)=97.9%). Steroids were not associated with increase in risk of infection. Conclusions A definitive role of corticosteroids in the treatment of ARDS in adults is not established. A possibility of reduced mortality and increased ventilator free days with steroids started after the onset of ARDS was suggested. Preventive steroids possibly increase the incidence of ARDS in critically ill adults.

Oxime therapy and outcomes in human organophosphate poisoning: an evaluation using meta-analytic techniques

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.

Tympanic temperature measurements: Are they reliable in the critically ill? A clinical study of measures of agreement*

Objective: Accurate measurement of temperature is vital in the intensive care setting. A prospective trial was performed to compare the accuracy of tympanic, urinary, and axillary temperatures with that of pulmonary artery (PA) core temperature measurements. Design: A total of 110 patients were enrolled in a prospective observational cohort study. Setting: Multidisciplinary intensive care unit of a university teaching hospital. Patients: The cohort was (mean ± sd) 65 ± 16 yrs of age, Acute Physiology and Chronic Health Evaluation (APACHE) II score was 25 ± 9, 58% of the patients were men, and 76% were mechanically ventilated. The accuracy of tympanic (averaged over both ears), axillary (averaged over both sides), and urinary temperatures was referenced (as mean difference, &Dgr; degrees centigrade) to PA temperatures as standard in 6,703 recordings. Lin concordance correlation (pc) and Bland–Altman 95% limits of agreement (degrees centigrade) described the relationship between paired measurements. Regression analysis (linear mixed model) assessed covariate confounding with respect to temperature modes and reliability formulated as an intraclass correlation coefficient. Measurements and Main Results: Concordance of PA temperatures with tympanic, urinary, and axillary was 0.77, 0.92, and 0.83, respectively. Compared with PA temperatures, &Dgr; (limits of agreement) were 0.36°C (−0.56°C, 1.28°C), −0.05°C (−0.69°C, 0.59°C), and 0.30°C (−0.42°C, 1.01°C) for tympanic, urinary, and axillary temperatures, respectively. Temperature measurement mode effect, estimated via regression analysis, was consistent with concordance and &Dgr; (PA vs. urinary, p = .98). Patient age (p = .03), sedation score (p = .0001), and dialysis (p = .0001) had modest negative relations with temperature; quadratic relationships were identified with adrenaline and dobutamine. No interactions with particular temperature modes were identified (p ≥ .12 for all comparisons) and no relationship was identified with either mean arterial pressure or APACHE II score (p ≥ .64). The average temperature mode intraclass correlation coefficient for test–retest reliability was 0.72. Conclusion: Agreement of tympanic with pulmonary temperature was inferior to that of urinary temperature, which, on overall assessment, seemed more likely to reflect PA core temperature.

Clinical profile and improving mortality trend of scrub typhus in South India

BACKGROUND Scrub typhus, a bacterial zoonosis caused by Orientia tsutsugamushi, may cause multiorgan dysfunction syndrome (MODS) and is associated with significant mortality. This study was undertaken to document the clinical and laboratory manifestations and complications and to study time trends and factors associated with mortality in patients with scrub typhus infection. METHODS This retrospective study, done at a university teaching hospital, included 623 patients admitted between 2005 and 2010 with scrub typhus. The diagnosis was established by a positive IgM ELISA and/or pathognomonic eschar with PCR confirmation where feasible. The clinical and laboratory profile, course in hospital, and outcome were documented. Factors associated with mortality were analyzed using multivariate logistic regression analysis. RESULTS The most common presenting symptoms were fever (100%), nausea/vomiting (54%), shortness of breath (49%), headache (46%), cough (38%), and altered sensorium (26%). An eschar was present in 43.5% of patients. Common laboratory findings included elevated transaminases (87%), thrombocytopenia (79%), and leukocytosis (46%). MODS was seen in 34% of patients. The overall case-fatality rate was 9.0%. Features of acute lung injury were observed in 33.7%, and 29.5% required ventilatory support. On multivariate analysis, shock requiring vasoactive agents (relative risk (RR) 10.5, 95% confidence interval (CI) 4.2-25.7, p<0.001), central nervous system (CNS) dysfunction (RR 5.1, 95% CI 2.4-10.7, p<0.001), and renal failure (RR 3.6, 95% CI 1.7-7.5, p=0.001) were independent predictors of mortality. Over 4 years, a decreasing trend was observed in the mortality rate. CONCLUSIONS Scrub typhus can manifest with potentially life-threatening complications such as lung injury, shock, and meningoencephalitis. MODS occurred in a third of our patients. The overall case-fatality rate was 9%, with shock, renal failure, and CNS associated with a higher mortality.

Toxicology of the newer neonicotinoid insecticides: Imidacloprid poisoning in a human

Imidacloprid, a potent neonicotinoid insecticide, is currently one of the best selling insecticides. We report a patient with clinical toxicity due to the ingestion of imidacloprid in a deliberate suicide attempt. The structure and mode of action of imidacloprid are discussed.

Ocular manifestations of Takayasu arteritis: a cross-sectional study.

Purpose: To detail the spectrum of eye manifestations in Takayasu arteritis and factors predisposing to its development. Methods: In this cross-sectional study, 61 patients with proven Takayasu arteritis who were identified during a 16-month period were evaluated for disease- and treatment-related eye manifestations. A fundus fluorescein angiography examination was performed where indicated and with the patients consent. Results: The mean (±standard deviation) duration of illness before ophthalmic evaluation was 55 ± 69 months. Decreased vision was the most common ocular symptom (30%). Thirty-five patients underwent fundus fluorescein angiography examination. Takayasu retinopathy was seen in 9 (15%), ocular ischemic syndrome in 4 (7%), and hypertensive retinopathy in 10 (16%) patients. The most common treatment-related ocular complication was steroid-induced cataract (23%). Other manifestations included iris neovascularization (n = 3), anterior ischemic optic neuropathy (n = 2), steroid-induced glaucoma (n = 1), neovascular glaucoma (n = 1), and uveitis (n = 1). Those manifesting Takayasu retinopathy and ocular ischemic syndrome had significantly (P < 0.05) lower blood pressure in both upper limbs compared with patients not manifesting ischemic retinopathy. A significant (P < 0.03) proportion of patients with Takayasu retinopathy and ocular ischemic syndrome had a nonrecordable right upper limb blood pressure. Conclusion: Disease- and treatment-related ocular complications are not infrequent in Takayasu arteritis. Arteritis involving the aortic arch and its branches favors the development of ischemic ocular complications.

Scrub typhus in South India: clinical and laboratory manifestations, genetic variability, and outcome

OBJECTIVES This study sought to document the clinical and laboratory manifestations, genetic variability, and outcomes of scrub typhus, an often severe infection caused by Orientia tsutsugamushi, in South India. METHODS Patients admitted to a large teaching hospital with IgM ELISA-confirmed scrub typhus were evaluated. Clinical examination with a thorough search for an eschar, laboratory testing, chest X-ray, and outcome were documented and analyzed. Additionally, a 410-bp region of the 56-kDa type-specific antigen gene of O. tsutsugamushi was sequenced and compared with isolates from other regions of Asia. RESULTS Most of the 154 patients evaluated presented with fever and non-specific symptoms. An eschar was found in 86 (55%) patients. Mild hepatic involvement was seen in most, with other organ involvement including respiratory, cardiovascular, and renal. Multi-organ dysfunction was noted in 59 (38.3%), and the fatality rate was 7.8%. Hypotension requiring vasoactive agents was found to be an independent predictor of mortality (p<0.001). The phylogeny of 26 samples showed 17 (65%) clustering with the Kato-like group and eight (31%) with the Karp-like group. CONCLUSIONS The presentation of scrub typhus can be variable, often non-specific, but with potentially severe multi-organ dysfunction. Prompt recognition is key to specific treatment and good outcomes. Further study of the circulating strains is essential for the development of a successful vaccine and sensitive point-of-care testing.

Acute intentional toxicity: endosulfan and other organochlorines

Introduction. Organochlorine pesticides continue to be used in several developing countries despite concerns regarding their toxicity profile. Endosulfan is an organochlorine recognized as an important agent of acute toxicity. Methods. In this retrospective study, the clinical features, course, and outcomes among patients with acute endosulfan poisoning requiring admission to the hospital during an 8-year period (1999–2007) were reviewed. Results. Among 34 patients hospitalized during this study period for alleged organochlorine poisoning, 16 patients with endosulfan poisoning were identified. The majority (75%) received initial treatment at a primary or secondary center. Neurological toxicity predominated, particularly low sensorium (81%) and generalized seizures (75%), including status epilepticus (33%). Other features observed included hepatic transaminase elevation, azotemia, metabolic acidosis, and leukocytosis. Mechanical ventilation was required in 69% and vasoactive agents in 19%. In-hospital mortality was 19%. There were no gross neurological sequelae at discharge. In three other patients who presented with organochlorine poisoning, the compounds ingested were lindane, endrin, and dicofol (n = 1 each). The course and outcomes in these patients were unremarkable and all three patients survived. Conclusions. Endosulfan is capable of high lethality and significant morbidity. The commonest manifestations are neurological although other organ dysfunction also occurs. In the absence of effective antidotes, restriction of its availability, along with prompt treatment of toxicity, including preemptive anticonvulsant therapy are suggested.

Advances in the management of organophosphate poisoning

Organophosphate (OP) poisoning is commonly encountered in agricultural communities. The mainstay of therapy in OP poisoning is the use of atropine. However, several other therapies have been evaluated. Although oxime has been the most studied antidote, results in humans have been disappointing and limited by the lack of well-designed, prospective, randomised controlled trials. The key factor in determining outcomes in OP poisoning appears to be the timing of antidote administration. Other adjuvants, such as magnesium, fresh frozen plasma and haemoperfusion appear promising, and need to be explored further. A multi-faceted approach may be the answer to improving outcomes in OP poisoning. This review evaluates the advances in OP management over the last 20 years.

Oximes in organophosphorus poisoning

Acute organic insecticide poisoning is a major health problem all over the world, particularly in the developing countries, where organophosphates (OPs) are the most common suicidal poisons with high morbidity and mortality and account for a large proportion of patients admitted to intensive care units. Other insecticides less commonly used are organocarbamates, organochlorides, and pyrethroids, which are less toxic and are associated with less morbidity and mortality. Patients with poisoning present with a wide spectrum of gastrointestinal, neurological, and cardiac manifestations. A strong clinical suspicion is necessary to make an early diagnosis and to start appropriate therapy. Treatment is primarily supportive and includes decontamination, anticholinergics, protection of the airway, and cardiac and respiratory support. The use of oximes has been controversial and may be associated with higher mortality owing to a higher incidence of type-II paralysis. They may have other toxic side effects. This paper reviews the literature on OP poisoning.