Anand Zachariah

Hair dye poisoning - an emerging problem in the tropics: an experience from a tertiary care hospital in South India

Super-Vasmol, a cheap, freely-available hair dye is emerging as a major cause of suicidal poisoning in India. It contains potential toxins including paraphenylene diamine, resorcinol, sodium ethylenediaminetetraacetic acid and propylene glycol which can result in multiorgan dysfunction. A retrospective study was conducted over 3.5 years (January 2006 – July 2009) of 13 consecutive patients with Super-Vasmol poisoning admitted to a tertiary care, referral hospital in South India. A chart review including records of clinical presentations, laboratory findings and treatment details was carried out. Eleven of the patients were women and the mean age was 27.2 years. The predominant clinical features were cervico-facial oedema and pain, cola-coloured urine and oliguria. Laboratory investigations revealed elevated hepatic transaminases (100%), leucocytosis (92.3%), elevated creatinine phosphokinase (92.3%), metabolic acidosis (84.6%), hypocalcaemia (61.5%), hyperphosphataemia (46.2%) and renal failure (38.5%). Eight of the patients were discharged with complete recovery. Trends towards a poor outcome were evident among the following patients: late presentation at our centre; when no gastric lavage was done at the primary-care centre; those requiring tracheostomy/intubation at the primary centre; presentation with a low Glasgow Coma Score or seizures; established renal failure; and those who subsequently require dialysis, mechanical ventilation or intensive care. Hair dye poisoning classically presents with cervico-facial oedema, severe rhabdomyolysis and renal failure. Early therapy with tracheostomy and aggressive forced diuresis are essential in order to prevent the high mortality associated with this toxin. It is imperative to raise public awareness of the potential toxicity of the dye as well as to educate physicians about the need for aggressive and early treatment.

Bioscavenger therapy for organophosphate poisoning – an open-labeled pilot randomized trial comparing fresh frozen plasma or albumin with saline in acute organophosphate poisoning in humans

Introduction. Traditional treatment of organophosphate poisoning (OP) with oximes has had limited success. Fresh frozen plasma (FFP) or albumin, acting as bioscavengers to mop up free organophosphate, has been recently proposed as a treatment modality. In this pilot open-label, three-arm, randomized controlled study exploring proof of concept, we evaluated if bioscavenger therapy had a role in OP. Patients and methods. Sixty patients with significant poisoning presenting within 12 hours, with suppression of pseudocholinesterase activity to < 1,000 U/L, were randomized to receive FFP (8 bags, 250 mL each over 3 days), 20% human albumin (4 × 100 mL over 3 days), or saline (2,000 mL over 3 days) in addition to atropine and supportive care. Pseudocholinesterase and organophosphate levels were measured pretreatment, post-infusion (Day 2, Day 3), and predischarge and expressed as mean ± standard error. The incidence of intermediate syndrome, need for mechanical ventilation, atropine requirement, and mortality were assessed. Results. Twenty patients received albumin and 19 patients each FFP or saline. FFP increased pseudocholinesterase levels (250 ± 44–1,241 ± 364 U/L) significantly (p = 0.007). Small, nonsignificant increases were observed with saline (160 ± 30–259 ± 78) and albumin (146 ± 18–220 ± 61). Organophosphate levels reduced in all 3 arms; no clear-cut trends were observed. We observed more cases of intermediate syndrome with FFP [10/19 (53%) vs. 5/20 (25%) vs. 5/19 (26%), FFP, albumin, and saline arms (p = 0.15)]. The interventions did not affect ventilatory requirements (14/19 vs. 15/20 vs. 14/19) or prevent delayed intubation. There were no differences in mean (±standard error) atropine requirement (in milligrams) in the first 3 days (536 ± 132 vs. 361 ± 125 vs. 789 ± 334) and duration (in days) of ventilation (10.0 ± 2.1 vs. 7.1 ± 1.5 vs. 7.5 ± 1.5) or hospital stay (12.4 ± 2.2 vs. 9.8 ± 1.4 vs. 9.8 ± 1.6). Two patients developed adverse effects with FFP. Mortality was similar (4/19 vs. 5/20 vs. 2/19, p = 0.6). Conclusions. Despite significant increase in pseudocholinesterase levels with FFP, this pilot study did not demonstrate favorable trends in clinical outcomes with FFP or albumin.

Mitochondrial ATP synthase inhibition and nitric oxide are involved in muscle weakness that occurs in acute exposure of rats to monocrotophos.

Organophosphate poisoning in the context of self-harm is a common medical emergency in Asia. Prolonged muscle weakness is an important but poorly understood cause of morbidity and mortality of the poisoning. This study examined mitochondrial function and its modulation by nitric oxide in muscle weakness of rats exposed to an acute, oral (0.8LD50) dose of monocrotophos. Muscle mitochondrial ATP synthase activity was inhibited in the rat in acute exposure to monocrotophos while respiration per se was not affected. This was accompanied by decreased mitochondrial uptake of calcium and increased levels of nitric oxide. Reactive cysteine groups of ATP synthase subunits were reduced in number, which may contribute to decreased enzyme activity. The decrease in ATP synthase activity and reactive cysteine groups of ATP synthase subunits was prevented by treatment of animals with the nitric oxide synthase inhibitor, L-NG Nitroarginine methyl ester, at 12 mg/kg body weight for 9 days in drinking water, prior to monocrotophos exposure. This indicated a role for nitric oxide in the process. The alterations in mitochondrial calcium uptake may influence cytosolic calcium levels and contribute to muscle weakness of acute organophosphate exposure.

A clinical study of renal tubular dysfunction in Cleistanthus collinus (Oduvanthalai) poisoning

Introduction. Self-poisoning through the ingestion of Oduvanthalai is common in South India. Mortality may occur because of arrhythmias, renal failure, shock, and respiratory distress. The mechanisms of toxicity are unclear. This prospective, clinical study was designed to assess renal tubular dysfunction because of Oduvanthalai poisoning. Methods. Thirty-two consecutive patients admitted with Oduvanthalai poisoning at a tertiary care hospital in South India, from June 2007 to August 2009 (26 months), were evaluated through history, physical examination, and laboratory studies. Following an interim analysis, additional studies of renal tubular function were performed on a subcohort of eight patients. These included the following: (1) urinary pH, daily serum, and urine anion gap; (2) 24-h urine protein and potassium; and (3) assessment of urine hexosaminidase and amino acid levels. Results. Metabolic acidosis (100%), which persisted at discharge (65.6%), hypokalemia (62.5%), and renal failure (15.6%), was apparent in the total cohort. Tests of renal tubular function on the subcohort revealed a normal anion gap, hyperchloremic, metabolic acidosis of renal etiology, defective urinary acidification, and hypokalemia with kaliuresis, indicative of distal renal tubular acidosis in six patients. Urinary hexosaminidase and amino acid levels, markers of proximal tubular dysfunction, were elevated in seven and two patients, respectively. Conclusions. Distal renal tubular acidosis is an important feature of Oduvanthalai poisoning. Proximal tubular injury and, in more severe forms, global tubular dysfunction with diminished glomerular filtration rate may occur.

Organophosphate-pyrethroid combination pesticides may be associated with increased toxicity in human poisoning compared to either pesticide alone

Abstract Background. Organophosphate (OP) poisoning results in significant toxicity while pyrethroid poisoning is associated with extremely low fatality. OPs can inhibit the detoxification of pyrethroid and increase the toxicity of the combination. We assessed whether mixed OP-pyrethroid poisoning impacted outcome in human poisoning. Methods. Patients were identified from a prospectively collected institutional poisoning database that incorporates demographic and outcome data of patients presenting with poisoning. Results. Of the 1177 poisoned patients admitted over 2 years, 32 presented with OP-pyrethroid (50% chlorpyrifos-5% cypermethrin mixture) poisoning (Group 1), 26 consumed 20% chlorpyrifos (Group 2), and 32 took 15% cypermethrin (Group 3). Seizures occurred in 15.6% (n = 5) with chlorpyrifos-cypermethrin poisoning, 18.8% (n = 6) with cypermethrin poisoning, and 3.9% (n = 1) with chlorpyrifos poisoning. Ventilatory requirements were 53.5% (17/32), 42.3% (11/26), and 15.7% (5/32) in Groups 1–3, respectively. Ventilator-free days (Mean ± SD) was significantly lower (p < 0.006) in Group 1 (20.9 ± 9.3 days) than those in Group 2 (26.1 ± 4.4 days) or 3 (27.8 ± 0.6). The median (inter-quartile range) hospital stay was 5.5 (4–19.5), 5 (5–6), and 1 (0.65–1.5) days, respectively, in the three groups. Four patients died in Group 1 (13%). None died in the other groups. Conclusion. Although confounded by the varying quantity of chlorpyrifos and cypermethrin in the different formulations, patients with mixed poisoning appear to have shorter ventilator-free days than patients poisoned by either of the pesticides alone. Further studies are required comparing patients poisoned by formulations with similar quantities of OP and pyrethroid or with analysis of blood pesticide concentration on admission.

Critical perspectives on the NIMH initiative “Grand Challenges to Global Mental Health”.

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A Networking Approach to Reduce Academic and Social Isolation for Junior Doctors Working in Rural Hospitals in India

INTRODUCTION Graduates from Christian Medical College (CMC) Vellore face many challenges while doing their service obligation in smaller hospitals, including academic and social isolation. To overcome these challenges, CMC aspired through its Fellowship in Secondary Hospital Medicine (FSHM), a 1-year blended on-site and distance-learning program, to provide academic and social support through networking for junior doctors working in rural areas. The purpose of this paper is to report the evaluation of the networking components of the FSHM program, with a focus on whether it succeeded in providing academic and social support for these junior doctors. METHODS A mixed method evaluation was done using written surveys for students and faculty and telephone interviews for students. Evidence for validity was gathered for the written survey. Criteria for validity were also applied for the qualitative data analysis. RESULTS The major strengths of networking with faculty and peers identified were that it provided social support,, academic support through discussion about patient management problems and a variety of cases seen in the hospital, guidance on projects and reminders about deadlines. Recommendations for improvement included use of videoconferencing and Yahoo Groups. CONCLUSION It is useful to incorporate networking into distance-learning educational programs for providing support to junior doctors working in rural hospitals.

Integration of academic learning and service development through guided projects for rural practitioners in India

Background: Christian Medical College Vellore (CMC) aspired through its Fellowship in Secondary Hospital Medicine (FSHM), a 1-year distance-learning program, to integrate academic learning and service development through guided projects for junior doctors working in small rural hospitals. Aim: The purpose of this article is to report the evaluation of the effectiveness of the project work in the FSHM program. Method: Mixed method evaluation was done using focus group discussion with students, written surveys for students and faculty, and telephone interviews with students and medical superintendents. Evidence for validity was gathered for the written survey. Criteria for trustworthiness were applied for the qualitative data analysis. Results: The major strengths of the project work identified were that students became aware of local health problems and how to deal with them, learned to work as a team, and had a sense of doing something useful. Recommendations for improvement were to have more interactions between guides and students. The benefits of projects to the hospital were providing improved clinical care, improved health systems, cost effective care management and benefits to the community. Conclusions: Service learning through guided project work should be incorporated into distance-learning educational programs for junior doctors working in rural hospitals.

Posaconazole: an emerging therapeutic option for invasive rhino-orbito-cerebral mucormycosis.

Posaconazole has significant activity against the Mucormycetes. However, data are limited on the clinical efficacy of posaconazole for treating rhino‐orbito‐cerebral mucormycosis (ROCM). The aim of this study is to assess the efficacy and safety of posaconazole in patients with ROCM. We included 12 consecutive adult patients admitted with ROCM and treated with posaconazole between January 2010 and February 2015. The main outcome of the study was the overall success rate (i.e. either complete or partial response) at the end of treatment. We also assessed serum posaconazole concentrations in a subgroup of patients. Of the 12 patients who received posaconazole, eight patients (66.6%) had complete resolution with median follow‐up of 6.5 months (range 2–24 months). Two patients (16.6%) had significant reduction of disease and two (16.6%) had marked residual disease on follow‐up. Uncontrolled diabetes was the predisposing factor in all except one patient. One patient developed diarrhoea on posaconazole, which settled without discontinuation of the drug. Posaconazole appears to be a safe and effective antifungal agent in diabetic patients with ROCM, especially in those who have toxicity with polyene therapy.

Clinical spectrum of yellow phosphorous poisoning in a tertiary care centre in South India: a case series.

Rodenticides such as yellow phosphorus are highly toxic compounds which are commonly used for pest control. Reports of yellow phosphorus poisoning from tropical nations is scanty. In this retrospective study, we report the clinical features, mortality and predictors of mortality among nine patients at a tertiary care centre in south India. Yellow phosphorus consumption was common among a younger age group of patients. The mean duration of presentation after consumption was five days. The most common clinical manifestations seen were abdominal pain and vomiting followed by a depressed sensorium. Features of acute liver failure including coagulopathy were seen in all patients. Despite all patients receiving supportive therapy, a poor outcome or death resulted in the majority. Early referral to a tertiary care centre, meticulous monitoring and supportive measures are key elements of patient management as there are no specific antidotes available at present. Increase in public and physician awareness to the toxin and implementation of preventive policies is of utmost importance.