Duration of vecuronium-induced neuromuscular blockade is shortened during hyperthermic intraoperative intraperitoneal chemotherapy

Abstract

Editor'It is well known that hypothermia augments the neuromuscular blockade induced by non-depolarizing neuromuscular blocking agents.1Caldwell JE Heier T Wright PMC et al.Temperature-dependent pharmacokinetics and pharmacodynamics of vecuronium.Anesthesiology. 2000; 92: 84-93Crossref PubMed Scopus (103) Google Scholar However, the effect of hyperthermia is not fully understood. Hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) is an effective method of treatment of intraperitoneal carcinomatosis,2Porcheron J Talabard J-N Breton C et al.Intraperitoneal chemo hyperthermia for peritoneal carcinomatosis: original modeling, clinical tolerance and results study about 30 patients.Hepatogastroenterology. 2000; 47: 1411-1418PubMed Google Scholar and induces an intraperitoneal temperature of about 42°C and an approximate core temperature of 39°C. In order to clarify the effect of hyperthermia on neuromuscular blockade, we observed the duration of action of vecuronium during HIIC in five patients of both sexes, ASA I or II, aged 59–71 yr. No patient had neuromuscular, renal or hepatic disease and none were receiving any drug known to interfere with neuromuscular transmission. All patients were premedicated with midazolam 2 mg i.m., atropine sulphate 0.5 mg i.m. and famotidine 20 mg i.m., 1 h before induction of anaesthesia. An i.v. infusion of lactated Ringer's solution was commenced and electrocardiography, pulse oximetry and non-invasive arterial pressure were monitored after arrival in the operating room. An epidural catheter was inserted at a lower thoracic level. General anaesthesia was induced with thiopental 4 mg kg−1. Immediately after induction of anaesthesia, the ulnar nerve was stimulated at the wrist with square-wave supramaximal stimuli of 0.2 ms duration, delivered in a train of four (TOF) mode at 2 Hz every 15 s using an Accelograph (Biometer International, Odense NV, Denmark). Contraction of the ipsilateral adductor pollicis was measured and recorded using accelerometry. When the evoked responses were stable, all patients were given vecuronium 0.1–0.12 mg kg−1 i.v. Tracheal intubation was performed after obtaining maximum depression of the first twitch response. Ventilation was adjusted to maintain end-tidal carbon dioxide partial pressure at 4.7–5.1 kPa using a Capnomac Ultima (Datex, Helsinki, Finland). Anaesthesia was maintained with sevoflurane 1.0% and nitrous oxide 67% in oxygen and intermittent administration of 5 ml of lidocaine 1.5% through the epidural catheter. Nasopharyngeal temperature was monitored. Maintenance doses of vecuronium 1 or 2 mg, depending on the patient's body weight, were administered when T1/T0 recovered to 25%. The duration of maintenance doses of vecuronium to spontaneous recovery of T1/T0 to 25% (DUR25) was measured. HIIC was initiated after removal of the tumour and reconstruction of the gastrointestinal tract. Cannulae were placed in the peritoneal cavity to allow for both inflow from and outflow to the pump. A cardiopulmonary bypass set with heat exchanger was used to rewarm the perfusate (normal saline) continuously,3Vocelka CR Anderson DL Crockett GI Hyperthermic intraoperative intraperitoneal chemotherapy for peritoneal carcinomatosis and sarcomatosis using a cardioplegia heat exchanger and a two-pump system: a case report.Perfusion. 2000; 15: 549-552Crossref PubMed Scopus (2) Google Scholar and the temperature of the perfusate was controlled to keep intraperitoneal temperature at 42°C. Fifteen minutes after the initiation of HIIC, cis-diaminedichloroplatinum was added to the perfusate. Forty-five minutes later, HIIC was stopped and the cannulae were removed. After HIIC, we could not continue measuring DUR25, as surgery had been completed. Statistical analysis was performed using analysis of variance (ANOVA, StatView Ver.4). Findings of P<0.05 were considered significant. Posthoc comparison was performed using Scheffe's F-test. Results are given as mean (sd). Before HIIC, nasopharyngeal temperature was 35.9–37.3°C. During HIIC, nasopharyngeal temperature significantly increased to 39(0.8)°C (P<0.05). The DUR 25 of each maintenance dose of vecuronium was 46.2(8.1)–65.2(9.9) min before HIIC, and significantly shorter at 28.2(3.9) min during HIIC (P<0.05). We have shown that duration of vecuronium-induced neuromuscular blockade is shortened during HIIC. Hyperthermia during HIIC may influence both the pharmacokinetics and pharmacodynamics of vecuronium. The elimination of vecuronium from blood depends mainly on hepatic uptake.4Astley B Clinical pharmacology of neuromuscular-blocking agents.in: Kaufman L Taberner PV Pharmacology in the Practice of Anesthesia. Arnold, London1996: 155-172Google Scholar Since the intraperitoneal temperature was kept at about 42°C during HIIC, it can be inferred that hepatic temperature was close to 42°C. Although we could not measure the blood concentration of vecuronium, accelerated hepatic uptake of vecuronium at high temperature is the most likely reason for the decreased duration of vecuronium-induced neuromuscular blockade we observed during HIIC. The pharmacodynamics of vecuronium-induced neuromuscular blockade are also known to be influenced by core temperature.1Caldwell JE Heier T Wright PMC et al.Temperature-dependent pharmacokinetics and pharmacodynamics of vecuronium.Anesthesiology. 2000; 92: 84-93Crossref PubMed Scopus (103) Google Scholar Since nasopharyngeal temperature was increased to 39°C during HIIC, a decrease in potency of vecuronium at this temperature may be another reason for the decreased duration of vecuronium-induced neuromuscular blockade we observed. T. Adachi1 T. Shinomura2 R. Nomura2 1Osaka, Japan 2Shiga, Japan