Anesthesia & Analgesia:
Letters to the Editor: Letters & Announcements
Section Editor(s): Shafer, Steven L.
Assistance Publique-Hôpitaux de Paris; Department of Anesthesiology and Intensive Care; Hôpital de Bicêtre; 94275 Le Kremlin Bicêtre, France; firstname.lastname@example.org
To the Editor:
We describe a case of delayed recovery from general anesthesia after a short-duration procedure in a 31-yr-old man, ASA physical status II, receiving chronic clozapine (200 mg BID) and alpraxolam (0.25 mg BID) for schizophrenia, who underwent repair of a fractured hip. The patient routinely took clozapine and alpraxolam at 8:00 am. The accident responsible for the hip fracture happened at 11:00 am. Anesthesia was induced 6 h later, and approximately 9 h after the clozapine and alpraxolam doses.
Before anesthetic induction, the patient was perfectly conscious, awake, and oriented. Without giving additional premedication we induced anesthesia with thiopental (500 mg), sufentanil (15 μg), and atracurium (40 mg). After tracheal intubation, we performed a fascia-iliaca compartment block using 30 mL of 0.2% ropivacaine. We maintained anesthesia with desflurane (0.8 MAC corrected for age) and nitrous oxide in oxygen (40%/60%). Before skin incision, we administered another dose of sufentanil (10 μg). We maintained his esophageal temperature at or higher than 36.5°C. Surgery lasted less than 1 h and was uneventful. The total anesthesia time was 1 h 25 min.
The patient awoke slowly from anesthesia. Spontaneous ventilation occurred 35 min after desflurane and nitrous oxide cessation. The patient opened his eyes 1 h 25 min after desflurane cessation. Tracheal extubation was possible 10 min later. The patient remained sleepy, and did not return to baseline consciousness until 4 h after arrival in the recovery room. We resumed his medications the morning after surgery, without any adverse effects and we saw no evidence of sedation.
Clozapine is a relatively new, atypical antipsychotic drug (1). By acting on dopaminergic receptor subtypes D1 and D2 and on α2 adrenergic receptor subtypes, clozapine appears to promote a better clinical response and fewer side effects than other neuroleptics (2,3). Clozapine also has sedative effects (4). There are few data concerning clozapine’s interaction with anesthetic drugs. An experimental study in rats found that halothane enhances clozapine-induced dopamine release in the striatum (5). Volatile anesthetics, but not thiopental, induce a concentration-dependant increase in dopamine’s metabolites release in rat striatum (6). Clozapine’s and desflurane’s effects on dopaminergic neurotransmission might be synergistic in their central nervous system depression.
In our case, the clozapine may have also shown synergy with alpraxolam, although the lack of sedation before anesthesia suggests this was not significant. Both the patient and family denied chronic sedation during postoperative questioning.
We have searched the medical literature and contacted both clozapine manufacturers in France (Novartis Pharma SAS for Leponex® and Panpharma for its generic drug). To the best of our knowledge, no similar interaction between anesthetic drugs and clozapine has been described. We believe delayed emergence from anesthesia may be an important side effect from the combination of inhaled anesthetics and clozapine.
Thomas Geeraerts, MD
Zeina Moghrabi, MD
Dan Benhamou, MD
Assistance Publique-Hôpitaux de Paris
Department of Anesthesiology and Intensive Care
Hôpital de Bicêtre
94275 Le Kremlin Bicêtre, France
1. Arnt J, Skarsfeldt T. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology 1998;18:63–101.
2. Kane JM. Pharmacologic treatment of schizophrenia. Biol Psychiatry 1999;46: 1396–408.
3. Doherty J, Bell PF, King DJ. Implications for anaesthesia in a patient established on clozapine treatment. Int J Obstet Anesth 2006;15:59–62.
4. Stanniland C, Taylor D. Tolerability of atypical antipsychotics. Drug Saf 2000;22: 195–214.
5. Adachi YU, Aramaki Y, Satomoto M, et al. Halothane attenuated haloperidol and enhanced clozapine-induced dopamine release in the rat striatum. Neurochem Int 2003;43:113–9.
6. Mantz J, Varlet C, Lecharny JB, et al. Effects of volatile anesthetics, thiopental, and ketamine on spontaneous and depolarization-evoked dopamine release from striatal synaptosomes in the rat. Anesthesiology 1994;80:352–63.