A Pilot Study Using Rocuronium to Prevent Intermediate Syndrome After Organophosphorus Insecticide Poisoning

Overview

Organophosphate pesticide poisoning causes close to 300 000 deaths per year worldwide. Many patients who ingest organophosphates require ventilation; of these patients approximately 50% die. Much of the mortality in these ventilated patients is secondary to intermediate syndrome. This is because OP pesticides inhibit acetylcholinesterase, causing an excess of acetylcholine at nerve synapses and the neuromuscular junction (NMJ). At the NMJ, the excess acetylcholine causes overstimulation and damage, which may lead to sudden respiratory arrest or prolonged ventilation and its associated complications.

The investigators believe that blocking these receptors using a neuromuscular blocking agent such as Rocuronium will protect the NMJ from damage and thus prevent intermediate syndrome and reduce number of intubated days and mortality.

In this pilot randomised controlled trial Rocuronium, a competitive nicotinic receptor antagonist, will be used to bind to the receptor at the neuromuscular junction and to block the effects of the accumulated acetylcholine. The effects of OP pesticide on cholinesterase in the blood will then be monitored and Rocuronium withdrawn using Sugammadex as the OP is eliminated from the body.

Full Title of Study: “Pilot Study – Assessing the Impact of Using a Neuromuscular Blocking Agent to Reduce Neuromuscular Junction Damage and Intermediate Syndrome in Organophosphorus (OP) Insecticide Poisoned Patients Requiring Ventilation”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: July 2016

Detailed Description

Primary outcome: Number of days intubated

Interventions

  • Drug: Rocuronium
  • Drug: Sugammadex
    • Effect of Rocuronium will be reversed at the appropriate time using Sugammadex 16mg/kg as a single dose which may be repeated once.

Arms, Groups and Cohorts

  • Active Comparator: Rocuronium with >95% inhibition
    • IV Rocuronium to be given: Bolus dose of Rocuronium 0.3 mg/kg to achieve >95% inhibition as indicated by Train of Four monitoring Continuous infusion of 1.5 mg/kg/hr to maintain level of inhibition To continue until two rises in butyrylcholinesterase seen or for a maximum of 5 days
  • Active Comparator: Rocuronium with 50% inhibition
    • IV Rocuronium to be given: Bolus dose of Rocuronium 0.3 mg/kg to achieve 50% inhibition as indicated by Train of Four monitoring Continuous infusion of 1.5 mg/kg/hr to maintain level of inhibition To continue until two rises in butyrylcholinesterase seen or for a maximum of 5 days
  • No Intervention: No Rocuronium
    • No Rocuronium will be given

Clinical Trial Outcome Measures

Primary Measures

  • Number of intubated days
    • Time Frame: Upto 5 days

Participating in This Clinical Trial

Inclusion Criteria

  • Male or female
  • Age over 16
  • Clinical diagnosis of OP insecticide poisoning
  • Admission to Intensive Care Unit for Ventilation
  • Informed consent from family
  • Train of four measurement > 50%

Exclusion Criteria

  • Age 16 or under
  • Pregnant
  • Consent not obtained from patient or patient's family

Gender Eligibility: All

Minimum Age: 17 Years

Maximum Age: 100 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Edinburgh
  • Collaborator
    • University of Peradeniya
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Indika Gawarammana, MD FRCPE PhD, Principal Investigator, South Asian Clinical Toxicology Research Collaboration
    • Michael Eddleston, MA PhD FRCP, Study Director, University of Edinburgh
    • Vasanti Pinto, MD FRCA FCARSCI, Study Director, University of Peradeniya
    • Vajira Weerasinghe, BDS MPhil PhD, Study Director, University of Peradeniya

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