Neuromuscular blockade of atracurium in permissive hypercapnic versus normocapnic swine undergoing laparoscopy.

Luca Bellini,Giulia Maria De Benedictis

doi:10.1371/journal.pone.0200439

Abstract

Neuromuscular blocking agents (NMBAs) are commonly used in experimental laparoscopy in swine undergoing carbon dioxide pneumoperitoneum. Hypercapnia may be present and may prolong NMBAs’ pharmacologic activity. The aim of this study is to evaluate the effect of permissive hypercapnia on the neuromuscular blockade of atracurium in swine. Six Large White swine weighing 30.5 ± 1.6 kg were sedated with intramuscular ketamine and medetomidine, after which anaesthesia was induced with propofol and maintained with sevoflurane. Atracurium 0.4 mg/kg was administered intravenously and the neuromuscular block monitored by acceleromyography during normocapnic and hypercapnic conditions (PaCO2 range 35–45 mmHg and 60–70 mmHg, respectively). Onset time and time to reach a train of four ratio (TOFR) of 0.7 and 0.9 were recorded. Cardiorespiratory parameters, electrolytes and acid-base status were measured under both conditions. Onset time was similar between the two conditions. Time to reach a TOFR of 0.7 and 0.9 (duration of the neuromuscular block) was longer in hypercapnic compared to normocapnic animals being 1325 ± 300 vs 855 ±111 (p = 0.002) and 1823 ± 434 vs 1218 ± 210 seconds (p = 0.005), respectively. Three hypercapnic swine had a TOF count of 2 and 1 instead of a count of 4 with fade. Permissive hypercapnia was associated with a decrease in pH from 7.444 ± 0.039 to 7.257 ± 0.025 (p < 0.001). No differences were observed for heart rate, end-tidal concentration of sevoflurane, body temperature and arterial haemoglobin saturation. Nonetheless, hypercapnic swine had a statistically significant increase in mean arterial pressure (p = 0.020) and plasma potassium concentration (p = 0.003). The values of PaCO2 achieved during hypercapnia were well tolerated in swine undergoing CO2 pneumoperitoneum for laparoscopy. Permissive hypercapnia increased the duration of the atracurium effect and caused an increase in the intensity of the neuromuscular block in few swine.

Highlights

The use of non-depolarizing neuromuscular blocking agents (NMBAs) is common during experimental laparoscopic procedures in swine [1,2,3,4,5]
The results of this study show that hypercapnic acidosis induced by pneumoperitoneum during laparoscopic surgery prolonged the duration of action of atracurium in swine
The duration of the neuromuscular block produced by a single injection of 0.4 mg/kg of atracurium is increased in swine undergoing laparoscopy under permissive hypercapnia

Summary

Introduction

The use of non-depolarizing neuromuscular blocking agents (NMBAs) is common during experimental laparoscopic procedures in swine [1,2,3,4,5]. Atracurium in pigs during permissive hypercapnia train of four ratio (TOFR) has recently been described to monitor neuromuscular blockade (NMB) in pigs [5]. Aggressive ventilator setting to manage hypercapnia may damage the lung. Moderate increases of CO2 arterial partial pressure (PaCO2) associated with a pH between 7.2 and 7.3 are often tolerated unless obvious contraindications are present [7]. Moderate or permissive hypercapnia has been associated with a protective effect towards ventilator-induced inflammation and simultaneously improves hemodynamic function [8]

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