Sleep deprivation and delirium are conditions commonly encountered in intensive care unit patients. Sleep in these patients is characterized by sleep fragmentation, an increase in light sleep, and a decrease of both slow wave sleep and rapid eye movement sleep. The most common types of delirium in this population are hypoactive and mixed-type. Knowledge about the mechanisms of sleep and delirium has evolved over time, but these phenomena are not yet well understood. What is known, however, is that different areas in the brainstem transmit information to the thalamus and cortex necessary for sleep-wake regulation. Delirium is related to an imbalance in the synthesis, release, and inactivation of some neurotransmitters, particularly acetylcholine and dopamine. The relationship between sleep deprivation and delirium has been studied for many years and has been viewed as reciprocal. The link between them may be ascribed to shared mechanisms. An imbalance in neurotransmitters as well as alteration of melatonin production may contribute to the pathogenesis of both phenomena. A better understanding of the mechanisms and factors that contribute to sleep deprivation and delirium can guide the development of new methods and models for prevention and treatment of these problems and consequently improve patient outcomes.

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Objectives: Trauma ICU patients may require high and/or prolonged doses of opioids and/or benzodiazepines as part of their treatment. These medications may contribute to drug physical dependence, a response manifested by withdrawal syndrome. We aimed to identify risk factors, symptoms, and clinical variables associated with probable withdrawal syndrome. Design: Prospective exploratory observational study. Setting: Trauma ICU in large medical center in Puerto Rico. Participants: Fifty patients who received opioids and/or benzodiazepines for greater than or equal to 5 days. Measurements and Main Results: Using an opioid/benzodiazepine withdrawal syndrome checklist developed from research in adult ICU patients, the Diagnostic and Statistical Manual of Mental Disorders-5, and the International Classification of Diseases, 10th Edition, we evaluated patients at baseline and for 72 hours after drug weaning was initiated. Patients received opioid/benzodiazepine (88%), opioid (10%), or benzodiazepine (2%). Probable withdrawal syndrome occurred in 44%, questionable withdrawal syndrome in 20%, and no withdrawal syndrome in 18 (36%). Signs that were more frequent in the probable withdrawal syndrome group were agitation, diarrhea, fever, tachypnea, lacrimation, and hyperactive delirium. Patients who developed probable withdrawal syndrome spent almost double the amount of time receiving mechanical ventilation, and length of stay was higher in both ICU and hospital when compared with patients in the other two groups. Age, cumulative opioid dose amounts, and previous drug (opioid/benzodiazepine, cannabis, cocaine, or heroin) use were associated with odds of developing withdrawal syndrome. With the addition of Richmond Agitation-Sedation Scale and delirium to the multilevel analysis, older age no longer had its protective effect, whereas increase in Richmond Agitation-Sedation Scale scores, delirium presence, and increased duration of mechanical ventilation were associated with higher odds of withdrawal syndrome. Conclusions: We identified probable withdrawal syndrome in a sample of trauma ICU patients through observation of several associated symptoms. Significant factors associated with withdrawal syndrome found in this study should be considered when caring for patients being weaned from opioids and/or benzodiazepines. Further validation of the opioid/benzodiazepine withdrawal syndrome checklist is recommended.

Iatrogenic withdrawal syndrome is an increasingly recognized issue among adult patients in the intensive care unit. The prolonged use of opioids and benzodiazepines during the intensive care unit stay and preexisting disorders associated with their use put patients at risk of developing iatrogenic withdrawal syndrome. Although research to date is scant regarding iatrogenic withdrawal syndrome in adult patients in the intensive care unit, it is important to recognize and adequately manage iatrogenic withdrawal syndrome in order to prevent possible negative outcomes during and after a patient’s intensive care unit stay. This article discusses in depth 8 studies of iatrogenic withdrawal syndrome among adult patients in the intensive care unit. It also addresses important aspects of opioid and benzodiazepine iatrogenic withdrawal syndrome, including prevalence, risk factors, and assessment and considers its prevention and management.