The Pharmacodynamics Of Continuous Infusion Of Homemade Atracurium In Patients Receiving Total Intravenous Anesthesia

BECKGROUND: Atracurium Besylate undergoes spontaneous biodegradation at body pH and temperature and does not depend on renal or biliary route for termination of action. If not for the side effects like histamine release, central nervous system active metabolite (Laudanosine) and problems of storage it would be closest to an ideal muscle relaxant. With proper and optimal monitoring of the depth of neuromuscular blockade, infusions are safe to use and give a stable and easily reversible neuromuscular blockade. The fear of accumulation and prolonged recovery time is becoming less and less as administration of short to moderate acting muscle relaxants like atracurium as continuous infusions have increased.OBJECTIVES: To examine the dose-response relationships of homemade atracurium after a single bolus and followed by continuous infusion under total intravenous anesthesia.METHODS: Eighty patients, ASA physical status Ⅰ or Ⅱ, scheduled to undergo elective surgical procedures were studied. Patients with hepatic, renal or neuromuscular diseases and those on medications known to affect neuromuscular blocking drugs were excluded. All patients were premedicated with injection atropine 0.01mg/kg intramuscularly 30 minutes before surgery. After 3-min of preoxygenation, anesthesia was induced with midazolam 0.04~0.05 mg/kg, fentanyl 2-4 μg/kg, followed by propofol 1-1.5 mg/kg, and maintained with oxygen 100 %, propofol 6-10 mg/kg/h and supplements of fentanyl 1-2 μg/kg as required. Mechanical ventilation was adjusted to maintain normocapnia. No potent inhalation anaesthetic was used. Before induction of anesthesia, the supramaximal stimulation need to be secured and the responses to train-of-four (TOF) nerve stimulation (2Hz, repeated at 20-s intervals) were stable at least 5-8 min. The ulnar nerve was stimulated using surface electrodes (ParaStim, USA) and the mechanical response of the adductor pollicis recorded using theneuromuscular transmission analyser (ParaGraph, USA). After bolus dose of atracurium 0.5 mg/kg, intubation was performed as soon as the first response to TOF stimulus (T,) fell below 5 %. If no response to TOF stimulation, at 6-min intervals, tetanic stimulation (50Hz) was applied for 5-s followed by a 3-s pause. On each occasion the tetanic stimulation was preceded by a 20-s period of 1-Hz stimulation, which was continued after the 3-s pause. When there was no response to the 1-Hz stimulation or the observed response had faded to zero, TOF mode of stimulation was reinstituted until 1-min preceding the next tetanic stimulation. The cycle was repeated until the first detectable response to the first stimulus in the TOF. The infusion was started when T| fell below 10 % again, at an infusion rate of 5 ug/kg/min. During surgery, the infusion rate used was regulated to maintain about 90—99 % Ti suppression and to provide adequate surgical relaxation. The infusion was discontinued approximately 20-min before termination of the operation. Spontaneous recovery of muscular function was then allowed to proceed. Double burst stimulation (3 pulses, 50Hz, 0.75-s interval; DBS3>3) was registered when extubating. The criteria for full recovery from neuromuscular blockade were a measured tidal volume of greater than 400 ml, and the ability to sustain a head lift for 5-s, and the TOF ratio greater than 70 %. RESULTS: Tracheal intubation was achieved in 176±44s after injection of a bolus dose of atracurium 0.5 mg/kg. Two patients showed slight transient flushing over the chest and neck following the administration of atracurium. No other adverse effects were noted. When no response to the TOF stimulation was recorded, a close linear relation was found between the time to first dectectable response to TOF stimulation and the square root of PTC (r= - 0.921, PO.001) .With 0.5 mg/kg, maximum block (Ti=0) developed within 203±47s, and recovery to 25 % twitch heights required 41.5±4.5 min after injection. The average infusion rate necessary to maintain approximately 90-99 % Ti suppression was 5.1±0.4 (ig/kg/min. No changes in mean arterial pressure or heart rate occurred during the infusion which were attributable to the use of atracurium. After termination of infusion, recovery index from 25 % to 75 % twitch heights were 14.9±3.7 min, and 44.1±6.1 min was required for recovery of adequate spontaneous respiration and neuromuscular function. The endotracheal tube was removed. At this point,...