Dexmedetomidine to Facilitate Drug Withdrawal (2003)

Received from Critical Health Systems, Inc., Raleigh, North Carolina.MANY patients are admitted to intensive care units (ICUs) from the emergency department for acute detoxification and withdrawal from alcohol or illicit drugs. The process of withdrawal is associated with significant psychomimetic and sympathomimetic phenomena. These patients require close cardiovascular system monitoring, intense nursing observation, and frequent interventions.In addition, critically ill patients who receive long-term sedative-analgesic therapy in the ICU develop functional tolerance. When they improve and sedative-analgesic medications are withdrawn, they experience withdrawal symptoms similar to those of patients addicted to alcohol, narcotics, or stimulants. 1–3Herein are two reports in which dexmedetomidine was used to facilitate the withdrawal process.A 49-yr-old woman was admitted to the ICU via the emergency room with altered mental status, unusual behavior, anxiety, and agitation. Initially, she was not forthcoming with her history, but later, she admitted to daily cocaine use for at least 2 yr. Her most recent cocaine exposure was approximately 24 h before admission, and her total habit was estimated at $200.00 per week. She also reported consumption of 1 quart of beer per day, or approximately 32 g alcohol. While in the emergency room, she became progressively agitated and combative, coupled with hypertension and tachycardia.On arrival in the ICU, she was extremely agitated but able to answer questions at the bedside. Her blood pressure varied from 150–200/70–90 mmHg, with a heart rate between 100 and 140 beats/min. Her chest was clear to auscultation without murmur, her abdomen was soft without masses, and she appeared to be neurologically intact. As part of the diagnostic differential to assess her hyperadrenergic state, we performed urine and serum toxicology screens along with an ABG to rule out cocaine intoxication and hypoxemia. Toxicology results were positive for cocaine. Our laboratory only qualifies the presence or absence of cocaine and does not quantify the amount.α-Adrenergic agonists, clonidine, and dexmedetomidine have been shown to alleviate withdrawal and excess sympathetic activity symptoms in animals and humans. 4–7Given the patient's agitation and poorly controlled hypertension, we decided to use dexmedetomidine for sedation. While in the ICU, a dexmedetomidine infusion was initiated with a loading dose of 1 μg/kg infused over 20 min, followed by a maintenance rate between 0.2 and 0.7 μg · kg−1· h−1to maintain a motor activity assessment score of 3, defined ascalm and cooperative, no external stimulus is required to elicit movement; patient is adjusting sheets or clothes purposefully; patient follows commands. 8She remained on dexmedetomidine for approximately 36 h. Her blood pressure ranged from 110/60 to 130/70 mmHg, with a heart rate of 80–100 beats/min. Immediately after the loading dose infusion was completed, she became quite calm. Because of the risk of seizures, she also received intermittent intravenous doses of lorazepam in 1- to 2-mg aliquots. While she was sleepy, she was also readily arousable and followed vocal commands. When dexmedetomidine was discontinued, a clonidine patch was placed to continue control of her hypertension, and oral lorazepam was administered for sedation and seizure prophylaxis.A 54-yr-old male was admitted for a laparoscopic repair of a massive abdominal wall incisional hernia. On the second postoperative day, he reported abdominal pain, he was febrile, and a three-position view of his abdomen revealed free intraabdominal air. He was returned to surgery to repair the leak from his terminal ileum. Postoperatively, he became bacteremic with secondary systemic inflammatory response syndrome, temperature greater than 38°C, heart rate greater than 90 beats/min, and respiratory rate greater than 20 breaths/min. During the next 4 days, he sequentially developed acute respiratory distress syndrome and multiple organ dysfunction syndrome with renal failure. Over his 6-week course in the ICU, in addition to mechanical ventilation, tracheostomy, and hemodialysis, he received continuous infusions of lorazepam and morphine. As his multiple organ dysfunction syndrome resolved and he was gradually liberated from mechanical ventilation, it became apparent that he was having symptoms of sedative-analgesic withdrawal, e.g. , tachypnea, tachycardia, and agitation. After 6 weeks of continuous benzodiazepine and opioid administration, he was given a full loading dose of dexmedetomidine (1 μg/kg over 20 min), maintained at the maximal infusion rate of 0.7 μg · kg−1· h−1. Over the course of 7 days, the dexmedetomidine infusion was gradually decreased according to his motor activity assessment score (target 3) and was ultimately discontinued. When he was subsequently removed from ventilatory support, he exhibited no further symptomology consistent with withdrawal phenomena.Physicians primarily observe withdrawal phenomena in those patients who are addicted to various drugs. However, those patients who experience multiple organ dysfunction syndrome or have prolonged courses in the ICU may also become functionally addicted or tolerant to therapeutic medications. Both conditions may result in withdrawal.For more than 20 yr, clonidine, an α-adrenergic agonist, has been used to ameliorate central psychomimetic, sympathomimetic, and cardiovascular symptoms of withdrawal. Given the acute nature of these patients’ symptoms, dexmedetomidine was used instead of clonidine because of its advantages, specifically rapid onset and titratability. The choice of dexmedetomidine allowed us to provide sedation, comfort, and hemodynamic control with a single agent. Because dexmedetomidine has a sixfold higher affinity for the α2subunit than clonidine, it is an excellent sedative-hypnotic agent with limited side effects, e.g. , hypotension. These two patients were gradually withdrawn over 36 h and 7 days, respectively.For the second patient, the utilization of dexmedetomidine was advantageous compared to a gradual tapering of benzodiazepines or opioids for three reasons. First, with the known benzodiazepine-opioid ventilatory effects of increasing the slope of the carbon dioxide response curve, the potential for additional ventilatory depression was not warranted in this patient with severely compromised respiratory function. 9Second, dexmedetomidine, with its pharmacodynamic properties, facilitated a more thorough neurologic examination. Third, the use of dexmedetomidine ameliorated the hemodynamic withdrawal phenomena associated with opioid withdrawal. 10Although propofol infusions could possibly be used in a fashion similar to that described for dexmedetomidine, this agent is not utilized in our ICUs. Furthermore, given the hyperadrenergic state of these patients, we believe the sympatholytic properties of dexmedetomidine make it a more suitable agent than propofol.At present, dexmedetomidine is only approved for 24 h of continuous infusion and for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. Other investigators, however, have reported more prolonged infusions of the drug, with good clinical outcomes and an absence of side effects. 11In the absence of pharmacokinetic and pharmacodynamic data, we titrated the infusion dose rate to a motor activity assessment score of 3. We observed no evidence of withdrawal from the effects of dexmedetomidine in either case. Despite highly dissimilar circumstances and medical histories, both patients remained calm, cooperative, and arousable while receiving dexmedetomidine. In addition, their vital signs remained stable.In summary, these reports illustrate the potential benefit of dexmedetomidine for sedation of patients during withdrawal from illicit drugs or the iatrogenic-induced tolerance that develops from extended treatment with sedative-analgesics in the ICU. Dexmedetomidine successfully controlled the psychomimetic and sympathetic symptoms of withdrawal, providing safe, calm, comfortable, and cooperative patient treatment.