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Remifentanil's Effect Is Not Prolonged in a Patient with Pseudocholinesterase Deficiency

1999; Lippincott Williams & Wilkins; Volume: 89; Issue: 2 Linguagem: Inglês

10.1213/00000539-199908000-00053

1526-7598

Jocelyn Manullang, Talmage D. Egan,

Anesthesia and Neurotoxicity Research

Remifentanil is a new synthetic opioid that provides rapid onset of analgesia with an ultrashort duration of action. Its unique pharmacokinetic profile stems from rapid metabolism by nonspecific esterases in blood and tissues [1]. Although preliminary evidence based on in vitro studies suggests that remifentanil's duration of action is not affected by pseudocholinesterase deficiency, this issue has not been formally examined in vivo. We present the case of a patient with previously undiagnosed pseudocholinesterase deficiency who experienced the need for prolonged mechanical ventilation after succinylcholine administration but who had no prolongation of remifentanil's effects. Case Report An otherwise healthy 23-yr-old woman weighing 68 kg presented for an oculoplastic procedure under general anesthesia after eye trauma 1 yr earlier. She reported no family history of anesthetic problems. She recalled previous eye procedures and a childhood appendectomy to have been uneventful in terms of anesthesia-related problems. After premedication with midazolam 2 mg IV, the patient was transported to the operating room, and standard monitors, including a peripheral nerve stimulator, were applied. After breathing oxygen, general anesthesia was induced with remifentanil 0.4 [micro sign]g [middle dot] kg-1 [middle dot] min-1 and propofol 150 mg IV. Succinylcholine 100 mg IV was given after 3 mg of d-tubocurarine IV. After tracheal intubation, anesthesia was maintained with 1% sevoflurane in oxygen/air and remifentanil 0.1-0.2 [micro sign]g [middle dot] kg-1 [middle dot] min-1. Neuromuscular blockade was monitored approximately every 10 min by stimulation of the ulnar nerve transcutaneously using train-of-four monitoring. No recovery of neuromuscular function was evident until 1 h after the administration of succinylcholine, with the appearance of one visible twitch. At 2 h after succinylcholine administration, the patient had four visible twitches of moderate intensity. Thirty minutes later, at the conclusion of the operation and anesthetic, the patient was responsive (i.e., able to obey commands) but had very poor ventilatory effort (the remifentanil and sevoflurane administration had been stopped approximately 8 min before the end of the procedure). The peripheral nerve stimulator continued to show a severely depressed response, and the patient could not initiate a head lift. The recovery of consciousness and mentation was rapid and routine and was consistent with the expected temporal profile of remifentanil and sevoflurane recovery. The patient was transported to the recovery room with her trachea intubated and her lungs mechanically ventilated. She received midazolam 2 mg IV and a continuous remifentanil infusion of 0.2 [micro sign]g [middle dot] kg-1 [middle dot] min (-1) for sedation and analgesia during this period. Frequent assessments of the patient's readiness for tracheal extubation were made. Four hours after the succinylcholine administration, the remifentanil infusion was discontinued, and adequate tracheal extubation variables were obtained (i.e., tidal volumes 350 mL, respiratory rate 24 breaths/min, SpO2 100% on 40% inspired oxygen). At this point, the patient was able to sustain a 5-s head lift, and her trachea was extubated shortly thereafter. The recovery profile of the remifentanil infusion in the recovery room was also rapid and typical of normal clinical use. In discussing the patient's care with the family postoperatively, her mother recalled that the patient had had a similar reaction to anesthesia after her childhood appendectomy. The patient had required a brief period of mechanical ventilation after this anesthetic, but no follow-up testing had been performed. Her subsequent anesthetics had been unremarkable. In particular, review of her last anesthetic, performed 9 mo earlier, revealed that it had been conducted as a monitored anesthesia case using a remifentanil infusion without any evidence of prolonged remifentanil effect. After discharge, a sample of the patient's blood was sent for pseudocholinesterase level, dibucaine number, and pseudocholinesterase phenotype estimate. The results of these studies, including normal values, are displayed in Table 1. Based on these test results, the patient would be expected to always exhibit a prolonged response to succinylcholine and mivacurium [2,3].Table 1: Postoperative Laboratory Testing ResultsDiscussion In this report, we summarize the perioperative events of a patient with previously undiagnosed pseudocholinesterase deficiency whose anesthetic included both a succinylcholine bolus injection and a remifentanil infusion. Her enzyme deficiency was suspected after a single dose of succinylcholine resulted in prolonged neuromuscular blockade requiring a period of mechanical ventilation postoperatively. Although her mother later recounted a similar anesthetic experience when the patient was a child, this had not been disclosed preoperatively. Subsequent laboratory testing confirmed an atypical pseudocholinesterase phenotype virtually diagnostic of a genotype homozygous for pseudocholinesterase deficiency. The patient had received remifentanil throughout her operation and during the period of mechanical ventilation in the recovery room. Within a few minutes of the remifentanil infusion being discontinued in the recovery room, she exhibited complete recovery from its sedative and respiratory depressant effects, and her trachea was extubated. Likewise, during her previous anesthetic using a remifentanil infusion, she was thought to have experienced a normal recovery from its effects. The findings of this clinical report are consistent with preliminary in vitro studies regarding remifentanil and pseudocholinesterase [4]. Selinger et al.1 showed that the in vitro hydrolysis of remifentanil in blood is associated with enzymes within the red cell and is not mediated by pseudocholinesterase, acetylcholinesterase, or carbonic anhydrase. In another in vitro study, Stiller et al.2 introduced remifentanil into blood harvested from five patients with known pseudocholinesterase deficiency and demonstrated that the rate of remifentanil metabolism was not different from that observed in control blood. Based on these in vitro studies, it is reasonable to assume that remifentanil will not have a prolonged effect in the pseudocholinesterase-deficient patient. However, this is the first report to confirm in vivo the clinical suppositions of the in vitro data. (1) Selinger K, Nation RL, Smith A. Enzymatic and chemical hydrolysis of remifentanil [abstract]. Anesthesiology 1995;83:A385. (2) Stiller RL, Davis PJ, McGowan FX. In vitro metabolism of remifentanil: the effects of pseudocholinesterase deficiency [abstract]. Anesthesiology 1995;83:A381. From a clinical perspective, remifentanil behaves as though its metabolism is entirely separate from the action of pseudocholinesterase, as suggested by the in vitro studies. This mode of metabolism is shared by some other drugs that are esters, including the short-acting beta-blocker esmolol. Esmolol's duration of action is also unaffected by pseudocholinesterase deficiency [7]. This report simply confirmed in the clinical setting what would be expected based on the basic science data. The early remifentanil literature raised some minor concerns as to whether remifentanil's duration of action would be prolonged in the patient with pseudocholinesterase deficiency [1,8], noting that the issue was not entirely clear and that the available data were still preliminary [9,10]. Ultimately, this issue was addressed by the in vitro studies of Selinger et al.1 and Stiller et al.2 The present report represents in vivo confirmation of their in vitro results. In summary, we report a case suggesting that patients with pseudocholinesterase deficiency have a normal response to remifentanil. This is consistent with in vitro data demonstrating that remifentanil metabolism seems to be unrelated to pseudocholinesterase activity.