Target-controlled Infusion Of Rocuronium During General Anesthesia: The Analysis On Effect-site Concentration

Background and objectiveThe safety of receptor has long been the focal point for much discussion abouteffect site of muscle relaxant, and there has been much controvercy over continuousinfusion of muscle relaxant. The objector claimed that the effect site of neuromuscularagent is at the acetylcholine receptor of end plate, and there is a safety margin of thereceptor occupancy of neuromuscular agent, so, muscular hypotonus only displaywhen muscle relaxant occupy more than70%of the receptors. On the contrary, thesupporter suggested that after induction with single and large dose of neuromuscularagent, the receptors will be saturated, and the agent molecule occupancy of receptor isaffected by blood drug level of the agent, therefore, modification of blood drug levelwill alter the occupance, then the muscle relaxation adjusted.Recently-developed target-controlled infusion (TCI) of muscle relaxant is a newmode of intravenous administration based on the combination of pharmacokineticsand information technology, which characterized by continuous induction andintubation, little fluctuation of neuromuscular block, adjustable target concentration associated with procedure demands during anesthesia maintenance, appropriaterelaxation extent, predictable recovery time of relaxation, rapid recovery ofspontaneous respiration and apparently low incidence of residual relaxation afterprocedure.Rocuronium is a non-depolarizing neuromuscular blocking agent with the mostrapid onset at present. It had no significant effect on hemodynamics, and is one of themost widely used one in clinical practice. More and more attention is paid onrocuronium due to its pharmacokinetics which is suitable for target-controlledinfusion. Recently, reports about muscle relaxant agent on target-controlled infusionare scarce and controversial. Some authors reported that when T1of TOF wasstabilized at the level of5%baseline value, the actually measured blood concentrationof rocuronium was1.00~2.06μg.ml-1. While domestic authors observed that under thesimilar propofol-remifentanil anesthesia, T1could be maintained at a level of below20%baseline value only on the premise of an effect-site concentration of rocuroniumof4.0~5.5μg.ml-1.This article aimed to observe the effect-site concentration of rocuronium undertarget-controlled infusion mode with a T1depression level of94-96%maintainedduring general anesthesia, and explor the feasibility of target-controlled infusionrocuronium.Materials and MethodsForty patients，aged18-55years，ASA I-II，body mass index (BMI18-27kg.m-2)，scheduled for elective surgeries under general anesthesia were enrolled．Allpatients suffered from neither any neuromuscular disease，nor hepatic，renal or braindysfunction．All patients did not received drugs affecting neuromuscular junctionfunction，and with a normal body temperature, electrolytic and acid-base imbalance,and without condition of difficult intubation. Room temperature was controlled at26C when patients arrived in the operationroom．A24G catheter was placed in the left median cubital vein for infusion ofmultiple electrolytes injection at a rate of10ml·kg-1·h-1．Systolic pressure(SBP)，meanarterial pressure(MAP)，diastolic pressure(DBP) of the upper fight arm，lead IIelectrocardiogram(ECG)，heart rate(HR)，pulse oxygen saturation(SpO2)，end-tidalpartial pressure of carbon dioxide(PETCO2) and Bispectral index (BIS) were recorded．Electrodes were placed on the body surface projection of left ulnar nerve at thewrist to record the response of the adductor pollicis. The accelomyography sensor waspositioned on the distal ventral part of the thumb，and the shell temperature sensorwas placed on the thenar eminence．The evoked response at the adductors pollicis wasmeasured by TOF-Watch-SX acceleromyography．A constant supra-maximal (60mA) train-of-four stimulation(four pulses0.2ms in duration，at a frequency of2Hz，2s in duration) was applied every15s．Sufentanil (0.3~0.5μg.kg-1) and propofol (2mg.kg-1) were injected slowly aftermonitor indicators were stable. When patients fell asleep, muscle relaxation monitorhad a transdermal50Hz titanic stimulation for5s, scaled with TOF after3min pause.Scaling was considered successfully when T1maintained at100%±10%in a stablephase for3min. After2×ED95rucoronium was injected for5s, patients were intubatedand had an intermittent positive pressure ventilation. A tidal volume of8-10ml.kg-1, arate of12-15times/breath, and inhaled oxygen concentration0.5were set to maintainpulse oxygen saturation (SpO2)100%and end-tidal carbon dioxide (PETCO2)35-40mmHg.All patients were randomly divided into two groups according maintenancemethods of anesthesia. Inhalation group (n=20), patients were inhaled sevoflurane andsupplemented with remifentanil (0.1-0.2μg.kg-1.Min-1). Target-controlled infusiongroup (n=20), patients were target-controlled infused on propofol effect-siteconcentration（2~4μg.ml-1），combined with remifentanil (0.1-0.2μg.kg-1.Min-1) tomaintained BIS40-60. When T1recovered to5%basal value, rocuronium began totarget-controlled infused on effect-site concentration, and the initial concentration of rocuronium was set at0.5μg.ml-1. T1was maintained in the range of4-6%basal valueby adjusting rocuronium target effect-site concentration according to the T1depression degree. Rocuronium was stopped infused half of an hour before the end ofoperation. Rocuronium was recorded target effect site concentration every3min. Thetime from rocuronium induction to T1recovering to5%was recorded. The time ofTOFr recovery to0.7was separately recoreded when T1returned to baseline value of25%,75%,90%after stopping rocuronium infusion. Adverse reactions were observed,such as-skin rash, hypotension, and high peak inspiratory airway pressure．All data were analyzed with SPSS11.0for windows．Measurement dates werepresented as mean±SD．The target-controlled infusion process of rocuronium wasdivided into four durations by per30min. The first duration was initial infusion for30min, the second duration was31-60min, the third duration was61-90min, the fourthduration was over90min. The different durations of target effect-site concentrationwere present by means and standard deviation. Independent sample T-test was used tocompare all demographic datas between groups, a p value <0.05was considered to besignificant．Results1. There had no statistically significant difference between two groups in age andBMI (p>0.05).2. The time from rocuronium induction to T1recovering to5%was is32.74±8.12min and32.26±4.76min separately in inhalation group andtarget-controlled infusion group (p>0.05).3. The thenar skin temperatures were32.8±0.5C in inhalation group and32.8±0.6C in target-controlled infusion group (p>0.05).4. In inhalation group, the average target effect-site concentrations of rocuroniumwere0.48±0.04μg.ml-1in the first duration,0.44±0.02μg.ml-1in the second duration,0.41±0.01μg.ml-1in the third duration, and0.35±0.05μg.ml-1in thefourth duration. In target-controlled infusion group, the average target effect-siteconcentrations of rocuronium were0.63±0.06μg.ml-1in the first duration,0.67±0.00μg.ml-1in the second duration,0.68±0.04μg.ml-1in the third duration（it didn’t make statistics in fourth duration due to a small sample number）.There had a significant difference between inhalation group and target-controlledinfusion group in the same duration (p<0.05). The average target effect-siteconcentrations of rocuronium had no difference between the second and thirdduration separately in inhalation group and in target-controlled infusion group(p>0.05), but had difference in the other durations(p<0.05).5. After stopping rocuronium infusion, T1returned to baseline value of25%,75%,90%were24.00±9.80min,46.11±9.58min,58.16±12.57min in inhalation group,and15.21±3.70min,30.95±6.63min,38.21±8.80min in target-controlled infusiongroup. The time of different durations had significant difference betweeninhalation group and target-controlled group. There also had statistical differenceseparately in inhalation group and target-controlled group(p<0.05).6. The time of TOFr recovery to0.7was67.35±17.53min in inhalation group and40.50±10.95min in target-controlled infusion group (p<0.05).7. No patient experienced any adverse events，including body movement，skin rash，hypotension and high peak inspiratory airway pressure．Conclusions1. Young and middle-aged patients, ASA I-II, can get stable muscle relaxant effectby target-controlled infusion of rocuronium during general anesthesia.2. The target effect-site concentration of rocuronium is lower in sevofluraneinhalation anesthesia than in target-controlled infusion of propofol, but therecovery time of muscle relaxant is significantly longer in sevoflurane inhalationanesthesia. 3. The target effect-site concentration of rocuronium is gradually reduced withduration during general anesthesia.