Incidence of Acute Withdrawal Syndrome in the ICU
Incidence of Acute Withdrawal Syndrome in the ICU
ABSTRACT & COMMENTARY
Synopsis: Acute withdrawal syndrome related to analgesic and sedative medications developed in one of three mechanically ventilated adult ICU patients with extended ICU care. The syndrome was more likely to occur in patients who had received neuromuscular blocking agents or had ARDS.
Source: Cammarano WB, et al. Crit Care Med 1998; 26:676-684.
Acute withdrawal syndrome is a clinically important problem which can increase morbidity, mortality, and hospital costs, as well as being distressful for patients and their families. The incidence of the syndrome, following the prolonged administration and weaning of analgesic and sedative medications, is unknown in adult ICU patients. As a first step toward preventing its occurrence, Cammarano and colleagues designed a retrospective pilot study to estimate the frequency of acute withdrawal syndrome in patients who were mechanically ventilated and required more than seven days of ICU care.
Medical records were reviewed for patients admitted to one of the surgery services in the trauma/surgical ICU over an 11-month period. Patients were excluded if they did not require mechanical ventilation, were in the ICU for less than seven days, were less than 18 years old, had a preexisting psychiatric diagnosis, head trauma or other intracranial pathology, were pregnant, or experienced withdrawal syndrome in the first seven days of ICU admission. There were 28 patients who met these criteria.
The patients' charts were reviewed to determine demographics, diagnoses, patterns of medication administration, duration of mechanical ventilation, and presence of the acute respiratory distress syndrome (ARDS). Specific medications recorded from the ICU and the surgical ward were opioids (morphine, fentanyl, hydromorphone, codeine, oxycodone), benzodiazepines (midazolam, lorazepam, diazepam), propofol, haloperidol, and nondepolarizing neuromuscular blocking agents (vecuronium, pancuronium, atracurium). Equipotent dosages were determined to facilitate analysis by converting all opioids to equivalent units of fentanyl and all benzodiazepines to equivalent units of lorazepam. (See Table 1.) The cumulative, mean daily, and peak daily doses were calculated for fentanyl and lorazepam equivalents, propofol and haloperidol, as well as the number of days a patient received each drug.
Table 1
Determination of equipotent dosage for fentanyl and lorazepam equivalents
Relative potency
Opioids
Fentanyl [1 mg IV] 1
Hydromorphone [1 mg IV] 1/20
Morphine [1 mg IV] 1/100
Acetaminophen + oxycodone 10 mg [1 tablet PO] 1/25
Acetaminophen + codeine 30 mg [1 tablet PO] 1/40
Benzodiazepines
Lorazepam [1 mg IV] 1
Midazolam [1 mg IV] 1/3
Diazepam [1 mg IV] 1/5
A composite set of withdrawal criteria was used to determine the presence of acute withdrawal syndrome. The composite was designed using established signs and symptoms of opioid or benzodiazepine withdrawal and a prospective physiologic and observational scoring tool previously used in human experimental models. (See Table 2.) For the study, a diagnosis of acute withdrawal syndrome was made if more than two each of the listed signs and symptoms were present and if there was no more likely explanation for their presence, if the diagnosis of acute withdrawal syndrome was made clinically, or if clonidine was used to treat the patient.
Table 2
Signs and symptoms of opioid and/or benzodiazepine withdrawal
| Symptoms | Signs |
| Drug craving | Sweating |
| Restlessness, irritability | Tachycardia |
| Sensitivity to pain | Vomiting |
| Nausea | Diarrhea |
| Cramps | Hypertension |
| Muscle aches | Fever |
| Dysphoria | Seizure |
| Insomnia | Tachypnea |
| Anxiety | Myoclonus |
| Delerium |
Nine of the 28 patients met the criteria for acute withdrawal syndrome. The syndrome was recognized clinically in four patients, and seven patients developed the syndrome after transfer to the ward. The most common signs were tachycardia, hypertension, and tachypnea. Irritability was the most frequent symptom. One patient had a withdrawal-related seizure that required ICU care. The patients experiencing withdrawal received significantly more days of neuromuscular blocking agent, propofol and lorazepam equivalent therapy, and they were also on the ventilator longer (39 vs 21 days) and were more likely to have ARDS. The mean daily doses of fentanyl equivalent (6 mg vs 1 mg) and lorazepam equivalent (38 mg vs 11 mg) were significantly greater in the patients experiencing withdrawal, while the non-withdrawal patients received significantly more haloperidol (11 mg vs 2 mg) per day. Although weaning rates of analgesics and sedatives were not significantly different, drugs were weaned faster in the patients that experienced withdrawal.
COMMENT BY DOREEN M. ANARDI, RN
The management of pain and anxiety is a patient's primary concern. Professional educational efforts have been directed to overcoming prejudices in providing adequate analgesic medications and medicating appropriately to provide patient comfort when neuromuscular blocking agents must be used. These efforts appear to be successful, since another professional learning need has now been identified, the prevention of acute withdrawal syndrome in patients who have received prolonged courses of opioids and/or benzodiazepines.
This study has a number of intriguing findings that deserve prospective investigation. The patients who experienced withdrawal syndrome received daily dosages that were much higher than recommended. Were these doses required to achieve adequate analgesia and sedation? Did they reflect the development of tolerance to the drugs being used? Tolerance was likely to develop in this population, as the duration of use was sufficient for physical tolerance to develop. The patients that received more haloperidol were less likely to experience withdrawal. This drug has been tested in alcohol withdrawal; does it also have some protective effect during drug withdrawal?
The more rapid weaning of drugs in patients experiencing withdrawal may be an important factor. As a patient's physiologic condition improves and ventilator weaning is anticipated, it may be difficult to follow the recommendation of weaning opioids in daily decrements of no greater than 5-10% in order to avoid withdrawal syndrome. This recommendation has not been tested in adult ICU patients, and there are no specific recommendations for weaning benzodiazepines.
While this study raises more questions than it answers, it does identify a population at high risk of developing acute withdrawal syndrome, provide a helpful review of signs and symptoms, and suggest future directions for research to facilitate the identification and prevention of this important clinical problem.
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