Post-operative delirium is a common complication following cardiac surgery and is associated with increased 1 year mortality. Currently there are no drug therapies to prevent delirium. Orexin is a neuromodulator thought to play an important role in disordered sleep, one of the instigators of delirium. Lembrorexant is an orexin antagonist, originally approved for sleep, that may also reduce the incidence of delirium. The Investigators propose a pilot study to determine the feasibility of a randomized controlled trial comparing Lembrorexant to placebo in patients following cardiac surgery in reducing the incidence of delirium, and improving sleep.
Admitted to hospital following open cardiac surgery through midline sternotomy
● Known severe obstructive sleep apnea diagnosed by polysomnography or STOPBANG score > 5
Periodic limb movement disorder or restless legs syndrome
Narcolepsy
Somnolence (Pasero Opioid Sedation Scale (POSS) >2)
Parallel
Lemborexant 5 mg
DrugThe intervention is the oral administration of a study drug containing lemborexant 5 mg daily between 2000h and 0000h for the first 7 days following extubating/initiation criteria is met or until their hospital discharge or until the first diagnosis of delirium, whichever occurs first. Initiation criteria: I. The participant has been extubated for at least 2 hours II. all other sedative medications have been discontinued for \>1 hour III. the participant has a Richmond Agitation and Sedation Scale (RASS) score of \>-1 or a Pasero Opioid-induced Sedation Scale (POSS) score \<3. If satisfactory sleep is not achieved with the 5 mg dose of the study drug, as defined by a Richards Campbell Sleep Score \<50 within 1 hour, another insomnia medication may be administered on participant request and clinician judgement. If participants develop delirium, the study drug will be discontinued.
Control (placebo) group
DrugThe control group will receive an oral placebo tablet daily between 2000h and 0000h for the first 7 days following when initiation criteria is met or until their hospital discharge, whichever occurs first. Initiation criteria: I. The participant has been extubated for at least 2 hours II. all other sedative medications have been discontinued for \>1 hour III. the participant has a Richmond Agitation and Sedation Scale (RASS) score of \>-1 or a Pasero Opioid-induced Sedation Scale (POSS) score \<3. If satisfactory sleep is not achieved with the 5 mg dose of the study drug, as defined by a Richards Campbell Sleep Score \<50 within 1 hour, another insomnia medication may be administered on participant request and clinician judgement. If participants develop delirium, the study drug will be discontinued.
Recruitment Feasibility
Recruitment will be deemed feasible if the investigators are able to achieve a minimum recruitment rate of 2 patients per week, with 80% of eligible patients approached consenting to participate.
Data Collection Adherence
Data collection adherence will be defined as 80% completion of delirium screening and sleep scores
Incidence of Postoperative Delirium
Delirium will be assessed using the screening tools ICDSC (ICU Delirium Screening Checklist) while the patient is in the Cardiac Surgery Intensive Care Unit (CSICU) and CAM (Confusion Assessment Method) when the patient is on the hospital ward. The ICDSC is an 8-item delirium screening instrument (range: 0-8 points) that evaluates a patient's level of consciousness, inattention, disorientation, hallucinations or delusions, psychomotor activity, inappropriate speech or mood, sleep disturbance and fluctuation of symptoms. The CAM is a tool that assesses for the four features of delirium: Feature 1 is an acute change in mental status or a fluctuating mental status, Feature 2, is inattention, Feature 3, is altered level of consciousness and Feature 4, is disorganized thinking. Assessors rate each feature as present or not present based on guiding questions.
Delirium Days
The number of days where delirium was present in the post-operative study period. Postoperative delirium is defined by either: ICU Delirium Screening Checklist (ICDSC) score \>3 in the cardiac surgical ICU (CSICU) or a positive Confusion Assessment Method (CAM) score on the postoperative surgical ward. The ICDSC is an 8-item delirium screening instrument (range: 0-8 points) that evaluates a patient's level of consciousness, inattention, disorientation, hallucinations or delusions, psychomotor activity, inappropriate speech or mood, sleep disturbance and fluctuation of symptoms. The CAM is a tool that assesses for the four features of delirium: Feature 1 is an acute change in mental status or a fluctuating mental status, Feature 2, is inattention, Feature 3, is altered level of consciousness and Feature 4, is disorganized thinking. Assessors rate each feature as present or not present based on guiding questions.
Adverse side effects
Adverse side effects other than delirium, including daytime somnolence. Daytime somnolence will be assessed by the Pasero Opioid-Induced Sedation Scale (POSS). For every instance of a study drug discontinuation, a form will be completed documenting the clinical reasons for discontinuation.
Sleep Quality
Sleep quality will be assessed using the Richards-Campbell Sleep Questionnaire (RCSQ) which is a validated instrument to assess sleep quality in critically ill patients. It evaluates perceptions of sleep depth, sleep latency, number of awakenings, time spent awake, and overall sleep quality. There are 5 questions with a 100 point Visual Analogue Scale with 100 being the best outcome and 0 being the worst. For example, the participant is asked to rate their sleep depth, "My sleep last night was a:" from 0 (light sleep), to 100 (deep sleep). This questionnaire will be administered by a trained member of the research team daily for the duration of administration of the study drug. The score is reported as the mean of the 5 questions.
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University of British Columbia
Lead sponsor
Eisai Inc.
Collaborator
Providence Health Care, British Columbia
Collaborator
St. Paul's Hospital, Vancouver (Providence Health Care)
Collaborator
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