Magnesium sulfate and calcium channel blocking drugs as antidotes for acute organophosphorus insecticide poisoning - a systematic review and meta-analysis.

INTRODUCTION: Treatment of acute organophosphorus or carbamate insecticide self-poisoning is often ineffective, with tens of thousands of deaths occurring every year. Researchers have recommended the addition of magnesium sulfate or calcium channel blocking drugs to standard care to reduce acetylcholine release at cholinergic synapses. OBJECTIVE: We aimed to review systematically the evidence from preclinical studies in animals exposed to organophosphorus or carbamate insecticides concerning the efficacy of magnesium sulfate and calcium channel blocking drugs as therapy compared with placebo in reducing mortality or clinical features of poisoning. We also systematically reviewed the evidence from clinical studies in patients self-poisoned with organophosphorus or carbamate insecticides concerning the efficacy of magnesium sulfate and calcium channel blocking drugs as therapy compared with placebo, in addition to standard therapy, in reducing mortality, atropine requirement, need for intubation and ventilation, and intensive care unit and hospital stay. METHODS: We performed a systematic review for articles on magnesium sulfate and calcium channel blocking drugs in organophosphorus or carbamate insecticide poisoning using PubMed and China Academic Journals Full-text (Medicine/Hygiene Series) databases and keywords: "organophosphorus or organophosphate poisoning", "cholinesterase inhibitor poisoning" OR "carbamate poisoning" AND "magnesium", "calcium channel blocker", or generic names of different calcium channel blocking drugs. Review of titles and abstracts revealed 2262 papers of potential relevance. After review of the full papers, a total of 19 papers relevant to the question were identified: five preclinical studies, nine case reports or small case series, and five clinical studies and trials. We also obtained primary data from three unpublished clinical trials of magnesium sulfate, providing data from a total of eight clinical studies and trials for analysis. All studies were of organophosphorus insecticides; no studies of carbamates were found. No pre-clinical or clinical studies of calcium channel blocking drugs and magnesium sulfate in combination were found. We extracted data on study type, treatment regimens, outcome, and side effects. Pre-clinical studies: Two rodent studies indicated a benefit of calcium channel blocking drugs treatment on mortality if given before or soon after organophosphorus exposure, in addition to atropine and/or oxime. In poisoned minipigs, treatment with magnesium sulfate after organophosphorus insecticide poisoning reduced cholinergic stimulation and hypertension. Of note, magnesium sulfate further suppressed serum butyrylcholinesterase activity in one rat study. Observational clinical studies: Calcium channel blocking drugs and magnesium sulfate have been used to treat cardiac dysrhythmias and hypertonic uterine contractions in organophosphorus poisoned patients. A small neurophysiological study of magnesium sulfate reported reversion of neuromuscular junction effects of organophosphorus insecticide exposure. Comparative clinical studies: Only four of eight studies were randomized controlled trials; all studies were of magnesium sulfate, of small to modest size, and at substantial risk of bias. They included 441 patients, with 239 patients receiving magnesium sulfate and 202 control patients. The pooled odds ratios for magnesium sulfate for mortality and need for intubation and ventilation for all eight studies were 0.55 (95% confidence interval [CI] 0.32-0.94) and 0.52 (95% CI 0.34-0.79), respectively. However, there was heterogeneity in the results of higher quality phase III randomized controlled trials providing more conservative estimates. Although a small dose-escalation study suggested benefit from higher doses of magnesium sulfate, there was no evidence of a dose effect across the studies. Adverse effects were reported rarely, with 11.1% of patients in the randomized controlled trials receiving the highest dose of magnesium sulfate requiring their infusion to be stopped due to hypotension. CONCLUSIONS: Both preclinical and clinical data suggest that magnesium sulfate and calcium channel blocking drugs might be promising adjunct treatments for acute organophosphorus insecticide poisoning. However, evidence is currently insufficient to recommend their use. Mechanistic and large multi-center randomized controlled trials testing calcium channel blocking drugs and magnesium sulfate are required to provide the necessary evidence, with careful identification of the insecticides ingested and measurement of surrogate markers of toxicity, including butyrylcholinesterase activity.

Using color flow detection of air insufflation to improve accuracy in verifying nasogastric tube position.

OBJECTIVES: Previous studies have shown that ultrasonography (USG), as an alternative to radiography, has a good accuracy in confirming nasogastric tube (NGT) position. Color flow detection of air insufflation is a novel approach in verifying NGT position. In our study, we aimed at evaluating its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy in confirming the NGT position, as compared with 2-dimensional (2D) USG. METHODS: The study was conducted on adult patients over a period of 38months in an emergency department in Hong Kong. 2D USG and color flow Doppler imaging were conducted for each subject. Chest X-ray was used as the gold standard for NGT position confirmation. RESULTS: 100 patients (59 males and 41 females) were recruited totally. Their mean age was 82. The sensitivity, specificity, PPV and NPV of 2D USG were 11.1% (95% CI 4.6%-17.6%), 100% (95% CI 100%-100%), 100% (95% CI 100%-100%), and 11.1% (95% CI 4.6%-17.6%) respectively. For color flow Doppler USG, the sensitivity, specificity, PPV and NPV were 90% (95% CI 83.7%-96.2%), 80% (95% CI 55.2%-100%), 97.6% (95% CI 94.3%-100%), and 47.1% (95% CI 23.3%-70.8%) respectively. The overall accuracy of color Doppler imaging was 89%, which was higher than that of 2D USG (20% only). CONCLUSIONS: Color flow detection of air insufflation improves the diagnostic accuracy of ultrasound in verifying NGT position. It is a quick investigation such that fasting time of patients and their length of ED stay can be shortened.