Medical complications during inpatient rehabilitation among patients with traumatic disorders of consciousness

Arch Phys Med Rehabil. 2013 Oct;94(10):1877-83. doi: 10.1016/j.apmr.2012.12.027. Epub 2013 Jun 2.


Objective: To assess the incidence of medical complications in patients with recent traumatic disorders of consciousness (DOCs).

Design: Data on adverse events in a placebo controlled trial of amantadine hydrochloride revealed no group difference, which allowed these events to be reanalyzed descriptively as medical complications experienced by the 2 groups collectively.

Setting: Eleven clinical facilities in the United States, Denmark, and Germany with specialty rehabilitation programs for patients with DOCs.

Participants: Patients (N=184) with nonpenetrating traumatic brain injury enrolled from acute inpatient rehabilitation programs between 4 and 16 weeks postinjury.

Interventions: Participants were randomized to receive 200 to 400mg of amantadine hydrochloride or placebo daily for 4 weeks, and followed for an additional 2 weeks. Adverse events were recorded and categorized with respect to their nature, timing, and severity.

Main outcome measure: Number, type, and severity of medical complications occurring during the 6-week study interval.

Results: A total of 468 medical complications were documented among the patients (.40 events per week per patient). More than 80% of patients experienced at least 1 medical complication, and 41 of these were defined as serious adverse events. New medical complications declined over time in rehabilitation and were not dependent on time since injury. Hypertonia, agitation/aggression, urinary tract infection, and sleep disturbance were the most commonly reported problems. Hydrocephalus, pneumonia, gastrointestinal problems, and paroxysmal sympathetic hyperactivity were the most likely to be severe.

Conclusions: Patients with DOCs have a high rate of medical complications early after injury. Many of these complications require brain injury expertise for optimal management. Active medical management appears to contribute to the reduction in new complications. An optimal system of care for DOC patients must provide expert medical management in the early weeks after injury.

Keywords: AE; Autonomic nervous system diseases; Brain injuries; CRS-R; Coma Recovery Scale-Revised; Consciousness disorders; DOC; DRS; Disability Rating Scale; Dyssomnias; Hydrocephalus; MCS; Muscle hypertonia; PSH; Persistent vegetative state; Pneumonia; Rehabilitation; TBI; Urinary tract infections; VS; adverse event; disorder of consciousness; minimally conscious state; paroxysmal sympathetic hyperactivity; traumatic brain injury; vegetative state.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amantadine / administration & dosage
  • Brain Injuries / complications*
  • Consciousness Disorders / drug therapy
  • Consciousness Disorders / etiology*
  • Consciousness Disorders / rehabilitation*
  • Dopamine Agents / administration & dosage
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Incidence
  • Inpatients
  • Male
  • Middle Aged
  • Rehabilitation Centers
  • Time Factors


  • Dopamine Agents
  • Amantadine