Acute Neurological ICU Sedation Trial (ANIST) — ANIST  

Sedation Clinical Trial

Official title: Acute Neurological ICU Sedation Trial (ANIST)

Status Completed

Clinical Trial Summary

Dexmedetomidine (Precedex, Hospira) is a "super" selective alpha2-agonist - 8-10x more avid binding to alpha2 receptors than clonidine - and may have particularly favorable characteristics as a continuous i.v. infusion sedative for critically ill neuroscience patients. Its combination of anxiolysis, analgesia, without undue lethargy may make it an ideal agent where frequent neurological examinations are important. Unclear, however, is whether Precedex is superior to current common i.v. sedation protocols, and if there are any undue concerns of this agent on cerebral physiology and cortical stimulation.

Clinical Trial Description

Dexmedetomidine has shown promise in small case series to be an efficacious sedative agent in the intensive care unit (ICU) setting, in both post-surgical and medical patients. A recent publication reported on the efficacy in a small series of medical patients (n=12), but as part of the exclusion criteria were any serious nervous system trauma or direct central nervous system (CNS) pathology.

A potential advantage of dexmedetomidine as a sedative agent compared to current popular classes of drugs, particularly propofol, benzodiazepines, and narcotics, is the nominal effect on reduction of level of arousal. Experience suggests that this agent may induce effective degrees of sedation without concomitant loss of attentive behavior and cognition following low levels of auditory or tactile stimulation. Thus, neurological assessment may be preserved while achieving the goal of a non-agitated or anxious patient. Additionally, the combination of both sedative/anxiolytic and analgesic action of dexmedetomidine may permit single drug use for both sedation and pain control during the post-operative and medical ICU period.

The cerebral effects of alpha2-agonists have been modestly studied in the clinical environment, and only in normal volunteers. As expected, cerebral blood flow decreased following initiation of the sedative, coincident with the expected diminishment of global cerebral metabolism. No studies have evaluated dexmedetomidine in patients suffering from neurological injury, the very population that may most benefit from the agent's sedative characteristics. Thus, it is imperative that a safety & efficacy study be carried out in a population of both medical and post-operative neuroscience patients. From an intraoperative perspective, dexmedetomidine has been effectively used as a sedative for both awake and sedation cases. Some evidence suggests prolonged cognitive deficits may persist beyond the sedative action of the drug.

One concern in the neuroscience patient population is laboratory evidence that alpha2-agonists may lower the seizure threshold. Such data has been shown for both clonidine and dexmedetomidine.

Therefore, to provide a comprehensive evaluation leading to successful safety and efficacy data for this sedative, it will be important to perform the following three studies. All three studies will be done concurrently but enrollment between the three studies will be mutually exclusive.

Objective 1: Evaluation of Quality of Sedation: Does dexmedetomidine provide superior sedative characteristics relative to current standard agents in patients with neurological dysfunction? The metrics for such a study will include -

1. Pharmacodynamic ease of sedation: time to goal, required nursing interventions to goal;

2. Quality & consistency of sedation: ability to examine the patient, number of required titration interventions;

3. Rapid weaning: time to off and no residual effect both hemodynamic and neurologic;

4. Systemic hemodynamic alterations requiring drug infusion adjustment or medical intervention;

5. Side effect and toxicity of sedative infusion: neurological dysfunction - cognitive, motor, sensory; electrolyte/hematological/metabolic disturbances, alteration of drug levels.

Objective 2: Alteration of Cerebral Physiology: Does Dexmedetomidine alter intracranial physiology either in a favorable or unfavorable manner? The metrics for such a study will include -

1. Measures of intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP);

2. Cognitive neurological state;

3. Cerebral saturation (venous) or direct cerebral oximetry (oxygen tissue level) in a subset population with specific intracranial device. ;

Related Conditions & MeSH terms

• Sedation

• NCT number: NCT00390871
• Study type: Interventional
• Source: Johns Hopkins University
• Status: Completed
• Phase: Phase 2
• Start date: May 2005
• Completion date: December 2007