Use of Analgesic Treatment to Reduce Signs of Pain in Patients With Disorders of Consciousness.

Use of Analgesic Treatment to Reduce Signs of Pain in Patients With Disorders of Consciousness: a Double-blind Placebo-controlled Clinical Study.

The purpose of this study is to characterize and improve pain and nociception management in patients with disorders of consciousness (DOC). This project is divided into two phases, a first phase to evaluate pain level and a second phase which consist of a clinical trial to evalute pain medication efficacy.

The main aim is to evaluate the use of the Nociception Coma Scale-Revised (NCS-R) and its cut-off score (i.e., 5) as an assessment and management tool to define guidelines for managing pain in patients with DOC. In this double-blind, placebo-controlled clinical study, we will evaluate the use of analgesic treatments in reducing pain in subacute/chronic patients. The project will also allow us to validate the NCS-R cut-off score defined previously.

The study will be performed within one week (i.e, 7 days) and consists of two phases:

• Phase 1 "Patients selection (D0)": Patients will be assessed by the NCS-R during experimental stimulation (rest, tactile, noxious) and mobilizations (physiotherapy). Patients with potential pain will be included in the phase 2.
• Phase 2 "Analgesic administration (D1 and D2)": double-blind placebo-controlled randomized clinical trial on potential responders identified in phase 1. A medical doctor of our team will suggest to the physician in charge to prescribe the dedicated medication. One placebo and one real treatment will be administered on day 1 and 2 by the nurses at least half-hour before the physiotherapy. Randomization between day 1 and 2 will be applied at that time.

For each day of phase 1 and 2, several assessments will be performed: NCS-R, CRS-R and spasticity assessment.

Inclusion Criteria:

• Have had an acquired brain injury with a loss of consciousness > 28 days (patients) or have no history of previous brain injury (healthy controls)
• Legally authorized surrogate available to provide informed consent.
• Diagnosis of vegetative/unresponsive (VS/UWS) or minimally conscious state (MCS) or emergence of the minimally conscious state without communication (eMCS; as defined by the CRS-R, see above).
• Medically stable (i.e., no systemic illness or disease).
• Patients with NCS-R score during mobilization above or equal to the previously determined cut-off score or NCS-R scores during mobilization equivalent to NCS-R score obtain during nociceptive stimulation will be included in the second phase of the study (i.e. D1 and D2).

Exclusion Criteria:

• History of developmental, neurologic, or major psychiatric disorder resulting in functional disability.
• Contraindication or unwillingness to discontinuing sedating and centrally-active drugs (benzodiazepine, long-acting sedating drugs) within 48 hours of assessment.
• Upper limb contusions, fractures or flaccid paralysis.
• Uncontrolled epilepsy and already on level 1 drugs