Antimuscarinic delirium (AMD) is a common and dangerous toxicology condition caused by poisoning by medications and other chemicals that block muscarinic receptors. Physostigmine, the standard antidote for AMD, currently has very limited availability in the United States due to an interruption of production. Recent case reports and small observational studies suggest that rivastigmine might be useful in the treatment of AMD, but there is not direct prospective evidence comparing rivastigmine to physostigmine or supportive care. In order to investigate the effectiveness of rivastigmine, the investigators propose a randomized, placebo-controlled clinical trial of rivastigmine for AMD. The investigators hypothesize that patients treated with rivastigmine for antimuscarinic delirium will experience more rapid resolution of agitation and delirium than those treated with placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
42
Rivastigmine 3mg by mouth once, followed by rivastigmine 1.5mg by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for a maximum of three doses
Matching oral placebo by mouth once, followed by placebo by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for a maximum of three doses
Washington University School of Medicine
St Louis, Missouri, United States
Time to control of agitation and delirium
Time from study drug administration to control of agitation and delirium, as defined by a Richmond Agitation-Sedation Scale (RASS) of 0 or -1 and a negative Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). RASS and CAM-ICU will be assessed by trained study personnel at the patient's bedside every 2 hours until sustained recovery (defined as absence of agitation and delirium on four consecutive assessments).
Time frame: Typically 8-36 hours after randomization
Duration of agitation and delirium
Total duration of time during which patient is experiencing agitation and delirium (defined and assessed as above)
Time frame: Typically 8-36 hours after randomization
Total amount of sedatives administered
Total amount of sedatives (antipsychotics, benzodiazepines, dexmedetomidine, propofol, fentanyl, ketamine) administered during the study period.
Time frame: Typically 8-36 hours after randomization
Use of sedative infusions
Any use of continuous sedative infusion (dexmedetomidine, benzodiazepine, propofol, fentanyl) during the study period.
Time frame: Typically 8-36 hours after randomization
Use of physical restraints
Any use of physical restraints during the study period
Time frame: Typically 8-36 hours after randomization
Disposition
Disposition to ICU, stepdown/intermediate care unit, or floor level of care
Time frame: Typically 8-36 hours after randomization
Time to medical clearance
Time from presentation to medical clearance by the toxicology consult service
Time frame: Typically 8-36 hours after randomization
Oversedation
Incidence of oversedation, defined as RASS lower than -2
Time frame: Typically 8-36 hours after randomization
Intubation
Incidence of intubation and mechanical ventilation during the study period
Time frame: Typically 8-36 hours after randomization
Seizure
Incidence of epileptic seizure during the study period
Time frame: Typically 8-36 hours after randomization
Gastrointestinal upset
Incidence of clinically significant gastrointestinal upset during the study period
Time frame: Typically 8-36 hours after randomization
Bradycardia
Incidence of any bradycardia (as defined using age-based heart rate cutoffs) during the study period
Time frame: Typically 8-36 hours after randomization
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