Therapy
 Continuous pralidoxime infusion versus repeated bolus
This review may be edited
Summary
Posted By: stuart green
E-Mail: stuart_green@health.qld.gov.au
Posted Date: 10 may 2007
Title: Continuous pralidoxime infusion versus repeated bolus
Authors: Kirti S Pawar, Ramesh R Bhoite, Chandrakant P Pillay, Sujata C Chavan, Dhananjay S Malshikare, Saraswati G Garad
Reference: Lancet 2006; 368: 2136–41
Link: Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract: Background The role of oximes for the treatment of organophosphorus pesticide poisoning has not been conclusively established. We aimed to assess the eff ectiveness of a constant pralidoxime infusion compared with repeated bolus doses to treat patients with moderately severe poisoning from organophosphorus pesticides.
Methods 200 patients were recruited to our single-centre, open randomised controlled trial after moderately severe poisoning by anticholinesterase pesticide. All were given a 2 g loading dose of pralidoxime over 30 min. Patients were then randomly assigned to control and study groups. Controls were given a bolus dose of 1 g pralidoxime over 1 h every 4 h for 48 h. The study group had a constant infusion of 1 g over an hour every hour for 48 h. Thereafter, all patients were given 1 g every 4 h until they could be weaned from ventilators. Analysis was by intention to treat. Primary outcome measures were median atropine dose needed within 24 h, proportion of patients who needed intubation, and number of days on ventilation. The study is registered at http://www.clinicaltrials.gov with the identifi er NCT00333944.
Findings 100 patients were assigned the high-dose regimen, and 100 the control regimen. There were no drop-outs. Patients receiving the high-dose pralidoxime regimen required less atropine during the fi rst 24 h than controls (median 6 mg vs 30 mg; diff erence 24 mg [95% CI 24–26, p<0·0001]). 88 (88%) and 64 (64%) of controls and high-dose patients, respectively, needed intubation during admission to hospital (relative risk=0·72, 0·62–0·86, p=0·0001). Control patients required ventilatory support for longer (median 10 days vs 5 days; diff erence 5 days [5–6, p<0·0001]).
Interpretation A high-dose regimen of pralidoxime, consisting of a constant infusion of 1 g/h for 48 h after a 2 g loading dose, reduces morbidity and mortality in moderately severe cases of acute organophosphorus-pesticide poisoning.
 
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
Uncertain. The authors describe a complex process of computer generating a block randomisation schedule (blocks of 4). The state that "The schedule remained concealed until after the trial’s completion" however they describe that "For each set of 40 patients, one of the ten blocks (of four) was chosen at random without replacement, and was then used for the next four consecutive patients to enrol. From this numbered block, one of the four numbered chits was chosen. On the basis of these two numbers, the computer program then allocated each patient to either the control or study group).
It is possible that allocation concealment was maintained, but this is a very complex non-standard approach.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
259 patients were assessed and 200 were enrolled. 100 in each traetment group. Follow-up on the 200 enrolled patients was complete.
2b. Were patients analyzed in the groups to which they were randomized?
Yes
3. Were patients, health workers, and study personnel blind to treatment?
Patients were blind but group allocation was revealed to medical staff (Duty doctors were unaware of the allocation sequence but were aware of the allocation once each patient was allocated to the study or control group).
4. Were the groups similar at the start of the trial?
Baseline demographics appear similar EXCEPT the treatment group had more diethyl pesticides (77 vs 59). This may have confounded the results to some degree.
5. Aside from the experimental intervention, were the groups treated equally?
Unsure. There appears to be but a rigid treatment protocol but it was not presented.
What are the Results?
1. How large was the treatment effect?
Primary outcomes: (control vs intervention)all [95%CI]p less than or equal to 0.0001
Median days ventilated: 10 vs 5 [5-6]
Median atropine dose: 30 vs 6 mg[24-26]
Intubated after randomisation; 19/31 vs 1/37[0.62-0.86]
Secondry outcomes:(control vs intervention)[95%CI] death:8 vs1 (p=0.0349)[0.016-0.98]
Pneumonia35 vs 8 (p=0.0001)[0.11-0.47]
2. How precise was the estimate of the treatment effect?
95%CI as above
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
Organophosphate poisoning uncommon in Australia, however given this study, higher dose pralidoxime infusion should be considered.
2. Were all clinically important outcomes considered?
Mortality and ventilator days major outcomes in ICU were considered.
3. Are the likely treatment benefits worth the potential harms and costs?
Yes

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Continuous pralidoxime infusion versus repeated bolus

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