Acute withdrawal syndrome in a butorphanol-treated patient: an adverse combination of opioids

Abstract

Editor—We recently experienced withdrawal syndrome in a patient which was probably elicited by administration of remifentanil and butorphanol. The patient was a 58-yr-old man (169 cm, 53 kg) with bronchiectasis who had tracheal intubation because of pneumonia and a tracheotomy was planned. The patient was known to have had episodes of CO2 narcosis previously. Therefore, tracheotomy under local anaesthesia was planned to avoid any residual effects from anaesthetics, narcotics, or both on the patient’s respiration after operation. During the previous 2 weeks, the patient had been routinely treated for insomnia with nocturnal (8:00 p.m. to 8:00 a.m.) administration of midazolam and butorphanol 1.2 and 0.12 mg h−1, respectively. The patient presented for surgery 7 h after the last administration. He was conscious and could communicate with gestures and lip movements. The vital signs were stable (arterial pressure 150/80 mm Hg, heart rate 90 beats min−1, Spo2 95%, and end-tidal CO2 4.8 kPa). To minimize the patient’s pain and agitation during the operation, administration of remifentanil 0.25 μg kg−1 min−1 was started, and after local infiltration with lidocaine 1% with epinephrine (1:300 000), a skin incision was made. Oxygen 2 litre min−1 mixed with air 4 litre min−1 was supplied and ventilation was manually supported when ventilatory frequency decreased. Spo2 was kept above 94% and end-tidal CO2 was maintained at 4.8−6.4 kPa. Approximately 30 min after initiation of the remifentanil administration, severe sweating and facial twitching were noted along with hypertension (170/85 mm Hg), tachycardia (140 beats min−1), and rhinorrhoea. The sweating was so severe that the sheet under the patient was drenched, and his pupils were dilated mildly. His facial expression was agonized, despite being conscious and denying any pain or discomfort. The surgery finished shortly after this and remifentanil was stopped. Within 30 min, the patient had regained sufficient spontaneous ventilation and his vital signs had returned to normal (arterial pressure 122/75 mm Hg and heart rate 115 beats min−1), and he was transferred to the general ward. The butorphanol and midazolam administration were restarted and the withdrawal signs resolved without further treatment. At the postoperative visit the next day, the patient’s appearance and vital signs were unremarkable. We diagnosed opioid withdrawal syndrome based on the modified Himmelbach’s scale.1Cammarano WB Pittet JF Weitz S Schlobohm RM Marks JD Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients.Crit Care Med. 1998; 26: 676-684Crossref PubMed Scopus (237) Google Scholar Withdrawal syndrome from midazolam was also considered. However, benzodiazepine withdrawal signs are characterized by hallucinations and restlessness and are quite different from what we observed in our patient; therefore, it was excluded from our diagnosis. Butorphanol is an opioid agonist–antagonist, which may cause withdrawal syndrome when given to patients in combination with high-efficacy opioids.2Weintraub SJ Naulty JS Acute abstinence syndrome after epidural injection of butorphanol.Anesth Analg. 1985; 64: 452-453Crossref PubMed Scopus (18) Google Scholar 3Preston KL Bigelow GE Liebson IA Butorphanol-precipitated withdrawal in opioid-dependent human volunteers.J Pharmacol Exp Ther. 1988; 246: 441-448PubMed Google Scholar Its elimination half-life after bolus administration is 3–5 h.4Ramsey R Higbee M Maesner J Wood J Influence of age on the pharmacokinetics of butorphanol.Acute Care. 1986; 12: 8-16Google Scholar However, the pharmacokinetics are different after long-term use, since this lipid soluble accumulates in tissue. Chronic administration has been reported to induce tolerance to its mu-agonist property and to antagonize other mu-agonists.5Smith MA Barrett AC Picker MJ Antinociceptive effects of opioids following acute and chronic administration of butorphanol: influence of stimulus intensity and relative efficacy at the mu receptor.Psychopharmacology (Berl). 1999; 143: 261-269Crossref PubMed Scopus (22) Google Scholar Our patient had daily administration for 2 weeks. No clinical signs or symptoms were observed before operation, thus we propose that was not due to stopping butorphanol but by its combination with remifentanil. Development of acute abstinence syndrome has been reported separately with the administration of either remifentanil or butorphanol.2Weintraub SJ Naulty JS Acute abstinence syndrome after epidural injection of butorphanol.Anesth Analg. 1985; 64: 452-453Crossref PubMed Scopus (18) Google Scholar 6Delvaux B Ryckwaert Y Van Boven M De Kock M Capdevila X Remifentanil in the intensive care unit: tolerance and acute withdrawal syndrome after prolonged sedation.Anesthesiology. 2005; 102: 1281-1282Crossref PubMed Scopus (31) Google Scholar However, in this case, the syndrome was precipitated by a combination of the two narcotics. Although the withdrawal symptoms precipitated by butorphanol were less potent compared with other mu-antagonists such as naloxone,3Preston KL Bigelow GE Liebson IA Butorphanol-precipitated withdrawal in opioid-dependent human volunteers.J Pharmacol Exp Ther. 1988; 246: 441-448PubMed Google Scholar we should be aware that some combination of opioid agonist and antagonist may synergistically cause unexpected side-effects in patients.