A phase II clinical trial to assess the safety of clonidine in acute organophosphorus pesticide poisoning

<p>Abstract</p> <p>Background</p> <p>An estimated 2–3 million people are acutely poisoned by organophosphorus pesticides each year, mostly in the developing world. There is a pressing need for new affordable antidotes and clonidine has been shown to be effective in animal studies. Our aim was to determine the safety of clonidine given as an antidote in adult patients presenting with signs or symptoms of acute organophosphate ingestion.</p> <p>Methods</p> <p>This study was a dose finding, open-label, multicentre, phase II trial. Forty eight patients with acute organophosphate poisoning were randomized to receive either clonidine or placebo: Four to receive placebo and twelve to receive clonidine at each dose level. The first dose level was an initial loading dose of 0.15 mg followed by an infusion of 0.5 mg of clonidine over 24 hours. The initial loading dose was increased to 0.3 mg, 0.45 and 0.6 mg. at all dosing levels however the subsequent infusion remained at 0.5 mg of clonidine over 24 hours.</p> <p>Results</p> <p>The baseline characteristics of both groups were similar. The trial was stopped after completion of the 3^rddosing level. At the 1^stand 2^nddosing level there were no reported adverse drug reactions. At the 3^rddosing level 5 patients (42%) developed significant hypotension during clonidine treatment that responded to intravenous fluids. There were no statistical differences in ventilation rate, pre and post GCS, and mortality rates over all levels.</p> <p>Conclusion</p> <p>Our findings suggest use of moderate doses of clonidine in acute organophosphate poisoning can be used without causing frequent clinical problems but that higher doses are associated with a high incidence of hypotension requiring intervention. Further studies are needed to study the efficacy of clonidine as an antidote in organophosphate poisoning.</p> <p>Trial registration</p> <p>Current Controlled Trial ISRCTN89917816.</p

Effect of a Brief Outreach Educational Intervention on the Translation of Acute Poisoning Treatment Guidelines to Practice in Rural Sri Lankan Hospitals: A Cluster Randomized Controlled Trial

<div><p>Background</p><p>In developing countries, including Sri Lanka, a high proportion of acute poisoning and other medical emergencies are initially treated in rural peripheral hospitals. Patients are then usually transferred to referral hospitals for further treatment. Guidelines are often used to promote better patient care in these emergencies. We conducted a cluster randomized controlled trial (ISRCTN73983810) which aimed to assess the effect of a brief educational outreach (‘academic detailing’) intervention to promote the utilization of treatment guidelines for acute poisoning.</p><p>Methods and Findings</p><p>This cluster RCT was conducted in the North Central Province of Sri Lanka. All peripheral hospitals in the province were randomized to either intervention or control. All hospitals received a copy of the guidelines. The intervention hospitals received a brief out-reach academic detailing workshop which explained poisoning treatment guidelines and guideline promotional items designed to be used in daily care. Data were collected on all patients admitted due to poisoning for 12 months post-intervention in all study hospitals. Information collected included type of poison exposure, initial investigations, treatments and hospital outcome. Patients transferred from peripheral hospitals to referral hospitals had their clinical outcomes recorded. There were 23 intervention and 23 control hospitals. There were no significant differences in the patient characteristics, such as age, gender and the poisons ingested. The intervention hospitals showed a significant improvement in administration of activated charcoal [OR 2.95 (95% CI 1.28–6.80)]. There was no difference between hospitals in use of other decontamination methods.</p><p>Conclusion</p><p>This study shows that an educational intervention consisting of brief out-reach academic detailing was effective in changing treatment behavior in rural Sri Lankan hospitals. The intervention was only effective for treatments with direct clinician involvement, such as administering activated charcoal. It was not successful for treatments usually administered by non-professional staff such as forced emesis for poisoning.</p><p>Trial Registration</p><p>Controlled-Trials.com ISRCTN73983810 <a href="http://www.controlled-trials.com/ISRCTN73983810" target="_blank">ISRCTN73983810</a></p></div

Wall chart to display guidelines on gastric decontamination.

<p>Wall chart to display guidelines on gastric decontamination.</p

Baseline characteristics of poisoned patients admitted to study hospitals in North Central Province of Sri Lanka.

<p>Baseline characteristics of poisoned patients admitted to study hospitals in North Central Province of Sri Lanka.</p

Hospital outcome with adjusted odds ratios to assess the effect of the intervention over the 12 months follow-up period in intervention and control hospitals in North Central Province of Sri Lanka.

#<p>Adjusted for covariates - poison type, hospital category.</p

Baseline characteristics of study cluster hospitals in North Central Province of Sri Lanka.

<p>Baseline characteristics of study cluster hospitals in North Central Province of Sri Lanka.</p

Participant flow chart.

<p>Participant flow chart.</p

Primary outcomes with adjusted odds ratios to assess the effect of intervention over the 12 months follow-up period in intervention and control hospitals in North Central Province of Sri Lanka.

#<p>Adjusted for covariates - poison type (except for sub-category of poison types), hospital category.</p