REVIEW ARTICLE

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REVIEW ARTICLE

The Effects of Perioperative and Intensive Care Unit Sedation on Brain Organ DysfunctionChristopher G. Hughes, MD,* and Pratik P. Pandharipande, MD, MSCI*February 10,2011.Increasing research and evidence, however, has implicated commonly prescribed sedative medications as risk factors for untoward events and worse patient outcomes, including brain organ dysfunction manifested as delirium and coma. The effect of sedatives on outcomes is also influenced by the depth of sedation, making it imperative to reduce total exposure to this class of medications. Juxtaposing the widespread necessity and use of sedation with the cost of acute and long-term cognitive dysfunction to patients and society, physicians must now strive to balance patients demands and requisite for comfort with their own oath to do no harm.

Delirium is an acute disturbance of consciousness accompanied by inattention, disorganized thinking,and perceptual disturbances that fluctuates over a short period of time.Though previously underdiagnosed and often considered to be an inconsequential occurrence associated with a patients perioperative course or critical illnessdelirium is now regarded as a form of acute brain organ dysfunction that is independently associated with worse clinical outcomes, including longer and more costly hospitalizations, longer times on mechanical ventilation, increased rates of hospital readmissions, increased risk of prolonged cognitive dysfunction, and 3-fold higher mortality.Furthermore, each additional day with delirium increases the risk of dying by 10%, and longer periods of delirium are also associated with greater degrees of cognitive decline when patients are evaluated 1 year after hospital discharge.50%80% of patients with critical illness developing delirium depending on the severity of illness and the need for mechanical ventilation . Although delirium, along with coma, represents acute brain dysfunction, many surgical patients (with concurrent anesthesia exposure) and critically ill patients also have long-term cognitive impairment (chronic brain dysfunction), which may persist for months to years after their hospitalization, significantly impacting their quality of life.There are numerous hypotheses that include neurotransmitter imbalance (e.g., dopamine, -aminobutyricacid, and acetylcholine), inflammatory perturbations (e.g., tumor necrosis factorI, interleukin-1, and other cytokines/chemokines), impaired oxidative metabolism, cholinergic deficiency, and changes in various aminoacid precursorsContributing sources can be summarizedas patient-related actors (e.g., age, previous dementia,diabetes, and heart failure) or iatrogenic risk factors (e.g.,psychoactive medications, hypoxemia, shock, and hypothermia)SEDATIVE AND ANALGESIC MEDICATIONS AND ACUTE AND CHRONIC BRAINDYSFUNCTIONNumerous associations between psychoactive medications and worsening cognitiveoutcomes in postsurgical patients have been published. Insufficient pain relief, however, has also been shown to be a risk factor for delirium and can contribute to sleep disturbances, disorientation, anxiety,and long-term effects such as posttraumatic stress disorder (PTSD).26 Morrison et al.27 conducted a prospective cohort study that enrolled patients with hip fractures, none of whom had preoperative delirium. Patients who received