Diaphragm Function Before and After Neuromuscular Blockade in Rats

Abstract

Neuromuscular blocking agents (NMBA; e.g., rocuronium bromide; ROC) are used during general anesthesia to inhibit nicotinic acetylcholine receptors and paralyze the diaphragm. Diaphragm function is inferred using the “train‐of‐four ratio” via electrical stimulation of a peripheral nerve. Since the diaphragm is clinically inaccessible, few studies have directly evaluated diaphragm function post‐reversal by NMBA. The current agent of choice for reversal of NMBA is neostigmine. However, neostigmine has multiple side effects such as hypotension, arrhythmia, and respiratory distress. Sugammadex (SUG) is a newer drug that inhibits ROC via direct encapsulation and is purported to have fewer side effects. We developed a model to assess diaphragm contractile function and oxygen levels in the rat using direct electrical stimulation of the phrenic nerve. The purpose of this study was to evaluate diaphragm contractile function and tissue oxygen levels before, during, and after administration of ROC and SUG. Female Sprague‐Dawley rats (n=6, 269 ± 3 g) were anesthetized with sodium pentobarbital (50 mg/kg, ip). A tracheal cannula was inserted to permit mechanical ventilation. Catheters were placed in the right common carotid artery for tracking arterial pressure and obtaining blood gases, and in the right jugular vein for administration of anesthetic and drugs. A midline abdominal incision was made to expose the diaphragm. The central tendon was cut and the left phrenic nerve was sectioned. Stimulating electrodes were placed on the right phrenic nerve. The central tendon of the right hemidiaphragm was connected to a load cell interfaced with a muscle tension analyzer. The right hemidiaphragm was stimulated via the phrenic nerve (1Hz, 6V) and partial pressure of oxygen in the interstitial space (PiO2; phosphorescence quenching) and contractile function were measured simultaneously. Contractile function and PiO2 were allowed to reach a new steady state after administration of both ROC and SUG. At the onset of diaphragm stimulation, PiO2 fell from 52 ± 3 to 21 ± 4 mmHg, while tension increased from resting (5.1 ± 0.3 g) to 17.4 ± 2.7 g during twitch contractions. Administration of ROC abolished twitches and tension fell rapidly to 4.0 ± 0.6 g within 30 ± 5 s. Concomitantly, PiO2 rose to 46 ± 3 mmHg over 224 ± 18 s. Reversal of ROC with SUG resulted in a restoration of twitch tension to 14.7 ± 2.2 g over 80 ± 13 s and a fall in PiO2 to 22 ± 4 mmHg over 144 ± 16 s. Once the new steady state was achieved, phrenic nerve stimulation was stopped and PiO2 recovered to 46 ± 4 mmHg over 225 ± 40 s. Throughout the experiment mean arterial pressure and heart were unaffected by either ROC or SUG. These results demonstrate the sugammadex effectively reverses the effects of rocuronium and rapidly restores diaphragm contractile function without impairing tissue oxygen levels or mean arterial pressure.Support or Funding InformationSupported by a grant from the KCOM Graduate Program Committee.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.