Toxic megacolon as a rare complication following atropine therapy due to organophosphate poisoning: A case report.

The main therapeutic basis for a case of organophosphate poisoning is a combination therapy which includes atropine as an anticholinergic drug and pralidoxime. If the poisoning is severe, a high dose of this combination of medicines may be needed, but this may cause serious side effects: paralytic ileus or even megacolon; however, these gastrointestinal events are very rare. Here, we report a case of organophosphate poisoning where atropine therapy was given and led to drug-associated toxic megacolon.

Accidental Intrathecal Injection of Ionic Contrast: Case Report and Review of the Literature.

BACKGROUND: Ionic contrast, if accidentally injected into the intrathecal space during routine imaging studies or interventional procedures, may significantly interfere with neuronal activity, potentially causing ascending tonic-clonic seizure syndrome and even death. As a result, ionic contrast is strictly contraindicated for intrathecal use. Rapid recognition of the condition followed by prompt management, typically involving aggressive cerebrospinal fluid (CSF) drainage, is critical to improving patient outcome. Lumbar drain has previously been well described as a management strategy. CASE DESCRIPTION: We present a case of accidental intrathecal injection of an ionic contrast agent, iothalamate meglumine, in a patient undergoing cervical epidural steroid injection. This patient was managed successfully with drainage of CSF using an external ventricular drain alone. CONCLUSION: Our literature review and analysis of the previously published cases demonstrate that aggressive CSF drainage is essential to improve outcomes, and in some cases an external ventricular drain alone may be effectively used.

Repeated pulse intramuscular injection of pralidoxime chloride in severe acute organophosphorus pesticide poisoning.

OBJECTIVE: This study aimed to clarify the efficacy of 2 therapies for patients with severe acute organophosphorus pesticide poisoning, including atropine adverse effects, the length of intensive care unit (ICU) stay, complications, and mortality. METHODS: A retrospective cohort study of 152 cases collected from May 2008 to November 2012 at 2 urban university hospitals was conducted. Patients admitted to the hospital for organophosphate poisoning were divided into 2 groups with different therapeutic regimens: group A was administered a repeated pulse intramuscular injection of pralidoxime chloride, and group B received the same initial dosage of atropine and pralidoxime chloride, but pralidoxime chloride intravenous therapy was administered for only 3 days, regardless of the length of atropine therapy. Subsequently, atropine adverse effects, length of ICU stay, complications, and mortality were statistically analyzed and compared between the 2 groups. RESULTS: The total dose of atropine was 57.40 ± 15.14 mg in group A and 308.26 ± 139.16 mg in group B; group A received less atropine than did group B (P = .001). The length of ICU stay in group A was reduced (P = .025), and group A had fewer atropine adverse effects (P = .002). However, there was no significant difference in the mortality or complication rate between the 2 groups (P > .05). CONCLUSION: In patients with severe poisoning, group A used less atropine, had fewer atropine adverse effects, and had a shorter ICU stay. We suggest that therapy should be started as early as possible using a sufficient amount of pralidoxime chloride started intramuscularly in combination with atropine and that the drugs should not be prematurely discontinued.

Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial.

BACKGROUND: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. METHODS AND FINDINGS: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. CONCLUSIONS: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.

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.

Incidence of intermediate syndrome in organophosphorous poisoning.

Seventy two patients admitted to the Intensive Care Unit following ingestion of organophosphorus compounds were studied prospectively with two different doses of pralidoxime (PAM). One group received 1 gm immediately after admission and no further PAM and the other group received infusion of PAM, 1 gm 8 hourly for four days (total 12 gms). The incidence of type II paralysis or intermediate syndrome was 47%. We observed a higher incidence in the 4 days of infusion of PAM group (61%) (20 patients) as compared to the single Bolus dose group (39%) (13 patients). Relative risk 1.48 (confidence interval = 0.9-2.4).

Improvement of motor function in multiple sclerosis by use of protopam chloride.

PAM, a cholinesterase reactivator, was administered orally and parenterally to 37 patients with multiple sclerosis and a control group of 24 patients with other neurological diseases and pain syndromes. The effects of the administration of this compound in these patients with and without electrical stimulation of the spinal cord were studied. The clinical response to the drug follows a known time course and is dose related. Administration of large doses orally or intravenously aggravates existing neurological dysfunction. With a dose of 1,000 mg intravenously, a characteristic response is the temporary appearance of new ophthalmological abnormalities, followed by significant improvement in motor control and behavior, which gradually subsides. Parenteral administration is superior to oral. Tolerance to the drug is observed. The presence of electrical stimulation of the spinal cord complements the action of the drug. When electrical stimulation is withdrawn, the effect of the drug reproduces the effect of the electrical stimulation. It is suggested there is a defect in cholinesterase in multiple sclerosis patients, and its reactivation may have a significant relationship to signs and symptoms.

Effects of nerve agent antidote and heat exposure on soldier performance in the BDU and MOPP-IV ensembles.

This study assessed the effects of nerve agent antidote (atropine/2-PAM chloride versus saline placebo) and heat-humidity (95 degrees F/60% RH versus 70 degrees F/30% RH) on repeated performance of militarily relevant psychological tasks while wearing the battle dress uniform (BDU) and while wearing chemical protective clothing (MOPP-IV). All BDU heat sessions (6 hours) were completed, but with some task impairments and a few subjective reactions. MOPP-IV heat sessions could not be continued beyond 2 hours; all tasks were impaired and subjective reactions were numerous and severe. Atropine/2-PAM significantly shortened endurance time for heat sessions in MOPP-IV.

Therapeutic dosing of pralidoxime chloride.

Pralidoxime chloride is a useful agent in the treatment of organophosphate poisoning. Poisindex, a widely used poisoning treatment resource, recommends dosing pralidoxime chloride as an intermittent iv infusion every 8-12 hours, whereas other authors have used continuous iv infusion with good results. Available animal data suggest that a serum concentration of 4 micrograms/ml may be a minimal level to protect against the toxic effects of organophosphates. Pharmacokinetic simulations, based on parameters obtained from healthy nonpoisoned subjects, show that pralidoxime levels fall rapidly to less than 4 micrograms/ml within 1.5-2 hours after a 1-g iv bolus. Continuous iv infusion (0.5 g/h) maintains pralidoxime levels greater than 4 micrograms/ml throughout the length of infusion. We conclude that continuous iv infusion of pralidoxime chloride may be the preferred method of administration in patients with acute organophosphate poisoning. Clinical trials will be necessary to document the effectiveness of this regimen.

Riscos no tratamento de intoxicaçöes por inseticidas organofosforados e carbamatos pela pralidoxima / Risks in the treatment of organophosphorous and carbamate insecticides poisonings with pralidoxime

A utilizaçäo da pralidoxima (Contrathion) nos casos de intoxicaçöes por organofosforados näo isenta o paciente de riscos de agravamento no quadro clínico. Isso se deve ao fato de que esse antidoto näo poderá ser considerado "inócuo" e sua administraçäo somente deverá ser instituída após o diagnóstico clínico e laboratorial da intoxicaçäo. Por outro lado, nos casos de intoxicaçöes por inseticidas carbamatos, seu uso é totalmente contra-indicado e o agravamento das intoxicaçöes é bastante comum

Myocardial and endocardial lesions in rabbit after acute poisoning with Intration and after treatment with some detoxifying agents.

The hearts of rabbits killed 24 hours after intoxication with Intration in the dose of LD50 and rabbits treated at the same time with PAM or atropine were studied pathomorphologically. Twenty-four hours after administration of Intration toxic lesions of the myocardium and endocardium were observed, which were more pronounced in rabbits treated simultaneously with the detoxifying agents as compared with those which received only Intration. The intensity of the changes was due to overdosage of the detoxifying agents, especially PAM which was particularly harmful.