Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 8  |  Issue : 4  |  Page : 567-572

Rocuronium continuous infusion versus intermittent bolus for maintaining suitable muscle relaxation and recovery status without using a peripheral nerve stimulator during anesthesia


Department of Anaesthesiology and Critical Care, Gauhati Medical College and Hospital, Guwahati, Assam, India

Date of Submission15-Sep-2014
Date of Acceptance02-Jul-2015
Date of Web Publication29-Dec-2015

Correspondence Address:
K Taye Mrinal
Department of Anaesthesiology and Critical Care, Gauhati Medical College and Hospital, Guwahati, Assam
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.172742

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  Abstract 

Introduction
The objective of anesthesia has always been to enable correction of surgical pathology with the best technique and minimum risk to the patient. The aim of the present study was to determine clinically, without using a peripheral nerve stimulator, whether continuous infusion or intermittent bolus dosing of rocuronium bromide yielded a better clinical condition during general anesthesia.
Patients and methods
The study was carried out on 60 adult patients. A common technique of general anesthesia was used in all patients. Patients were randomized to receive either a continuous infusion (group I, n = 30) or intermittent bolus dosing (group II, n = 30) of rocuronium bromide. Intraoperatively (a), hemodynamic parameters (heart rate and arterial pressure), (b) clinical relaxation by a grading technique, (c) total drug requirement, (d) recovery status by modified Steward score were assessed and were compared between the two groups.
Results
The mean heart rate and mean arterial pressure at different time intervals after intubation with rocuronium were not significantly different between the two groups. The total drug requirement was significantly greater in patients who received an intermittent bolus dose of rocuronium than those who received a continuous infusion. Clinical relaxation and recovery status in patients receiving rocuronium infusion were significantly better.
Conclusion
Rocuronium infusion offers a better and stable degree of relaxation compared with intermittent bolus dosing for intermediate duration of operation, which can be assessed using the clinical relaxation grading system. Rocuronium is a rapidly acting and hemodynamically stable nondepolarizing muscle relaxant with fewer drug requirements and provides better quality of recovery status during a continuous infusion.

Keywords: comparison, continuous infusion, intermittent bolus, rocuronium, without peripheral nerve stimulator


How to cite this article:
Mrinal K T, Dilip K S, Sulakshana K, Panchami B. Rocuronium continuous infusion versus intermittent bolus for maintaining suitable muscle relaxation and recovery status without using a peripheral nerve stimulator during anesthesia . Ain-Shams J Anaesthesiol 2015;8:567-72

How to cite this URL:
Mrinal K T, Dilip K S, Sulakshana K, Panchami B. Rocuronium continuous infusion versus intermittent bolus for maintaining suitable muscle relaxation and recovery status without using a peripheral nerve stimulator during anesthesia . Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2019 Sep 20];8:567-72. Available from: http://www.asja.eg.net/text.asp?2015/8/4/567/172742


  Introduction Top


The objective of anesthesia has always been to enable correction of surgical pathology with the best technique and minimum risk to the patient and the role of the anesthesiologist is to maintain the physiological parameters of the patient as close to normal as possible. With the help of neuromuscular blocking agent and inhalation anesthetics, the desired level of anesthesia can be achieved easily and safely according to the requirements of the surgeon without considerable cardiovascular and central nervous system depression of the patient. Org 9426, now known as rocuronium bromide, has a rapid onset time, an intermediate duration of action, and rapid recovery characteristics, coupled with cardiovascular stability, almost no histamine release, or other side effects; it best fulfills the requirements of an ideal neuromuscular blocking agent [1],[2] . Although a nerve stimulator is a better means of assessment of neuromuscular blockade, we were confined to clinical assessment and evaluation with some modified grading and scoring systems. Adequate muscle relaxation for long surgical procedures and in the ICU can be provided by administration of an intermediate-acting muscle relaxant through intermittent bolus dosing or a continuous infusion. Use of a long-acting muscle relaxant may result in progressive accumulation, slow recovery, and possible problems in reversal, particularly in patients with organ disease. For long procedures, it is particularly inconvenient to administer repeated bolus doses for muscle relaxation frequently. The use of relaxants by infusions not only provides steady-state relaxation and avoidance of overdose but also has the advantage of possibility of relatively easy reversal [3],[4] . The aim of this study was to determine clinically whether a continuous infusion or an intermittent bolus dosing of rocuronium bromide yielded better clinical conditions for operation.


  Patients and methods Top


The present clinical comparative study on the use of continuous infusion and intermittent bolus dosing of rocuronium was carried out in the operating theaters of the urology and surgery department, Gauhati Medical College and Hospital, Guwahati, from March 2003 to February 2004. The study proposal was reviewed and approved by the institutional ethics committee of the hospital. The procedure was explained to the patients and written consent was obtained preoperatively.

Selection of cases

The study was carried out on 60 adult patients, 30 in each group, of ASA I and II of either sex of different ages (20-60 years) undergoing a surgical procedure of intermediate duration. Patients with the following conditions were excluded from the study: patients with neurological or skeletal system disorders, gross cardiovascular, or metabolic disorders, pregnant patients, patients receiving drugs that could interact with a neuromuscular blocking agent, patients with potential airway problems and pulmonary ailments, patients admitted for emergency surgery, and patients with a history of an allergic reaction to a neuromuscular blocking agent.

Technique

A common technique of general anesthesia was used in all patients included in the present study. All patients received the same premedication with intravenous fentanyl 2 mg/kg, glycopyrrolate 0.2 mg, ranitidine hydrochloride 50 mg, and ondansetron 4 mg. Standard monitoring of patients included ECG, pulse oximetry, and noninvasive blood pressure. Patients were preoxygenated for 3 min with 100% oxygen. All the patients were administered intravenous propofol 2 mg/kg and maintained with classical nitrous oxide, oxygen, and halothane inhalational anesthetic. The neuromuscular blockage was reversed with neostigmine.

A bolus dose of intravenous rocuronium bromide 0.9 mg/kg was injected (tracheal intubating dose) in both groups. The concentration for infusion was prepared as 30 mg of rocuronium bromide in 60 ml of 5% plain dextrose, which yields a concentration of 0.5 mg/ml. Patients were randomized to receive either a continuous infusion of rocuronium bromide 0.5 mg/kg/h and titrated according to the clinical assessment of the patient (group I) or an intermittent bolus dose of 0.15 mg/kg (group II) administered according to grade 3 status of relaxation. Infusion was started at 5 min following an intubating bolus dose of rocuronium and stopped at the beginning of skin suture.

Recording of intraoperative parameters

Hemodynamic parameters, which included heart rate and mean arterial pressure, were recorded preoperatively, at 5, 10, and 20 min following intubation, and then at 15 min intervals throughout the entire operation in both the groups and compared accordingly. Clinical relaxation was assessed by a grading system formulated from various clinical manifestations and its correlation to nerve stimulator findings from a standard textbook, that is grade 4, complete relaxation; grade 3, rigidity in reservoir bag/increased resistance; grade 2, diaphragmatic movements/jerks; grade1, tension/rigidity of the abdominal wall/operated part (assessed by surgeon); and grade 0, limb movements. The degree of clinical relaxation were plotted at 15 min intervals, where we compared how uniformly the patients could maintain the degree of clinical relaxation all through the operation in both the groups. The total drug requirement was calculated and compared in both groups. An intubating bolus dose, followed by infusion required in group I and an intubating bolus dose, followed by total intermittent bolus doses required were calculated. The average total drug requirement per minute per patient was evaluated as mg/kg/min in the intermittent bolus dosing group for an easier comparison. Recovery status was recorded using the modified Steward score, where patients with higher scores showed better recovery status. Then, we compared the score of the patients of both groups. The modified steward score was as follows:

  1. Consciousness: awake-2, responding to command-1, not responding-0.
  2. Airway: coughing on command-2, maintenance of good airway-1, supportive airway maintenance-0.
  3. Movements: head raising and sustain for 5 s.
  4. Head raising-3, moving limbs purposefully-2, no purposeful movements-1, no movements.
Head rising and sustain for 5 s was added to the original steward score. Several useful scoring systems have been devised from the simple score designed by Steward for more complex examples [5] . Monitoring of residual neuromuscular paralysis by a peripheral nerve stimulator would have aided the detection of residual paralysis. In our study, patients with delayed recovery were shifted to the ICU with a tube in situ. Sugammadex is the first line of drug for difficult recovery from rocuronium block. Sugammadex encapsulates rocuronium and can reverse even a deep block in less than 3 min, but this drug is not available in our center [6] . However, patients with delayed recovery were excluded from our study.

Statistical analysis

The total sample size was 60 patients, with 30 in each group. This was a randomized-controlled trial where randomization was achieved by computer-generated numbers. The sequence was generated by a statistician. Data were reported as mean ± SD, median, and n (%) where ever appropriate. The demographic data were analyzed using the c2 -test. Parametric and nonparametric data of the two groups were compared and analyzed using a two-tailed Student's t-test and the Mann-Whitney U-test, respectively. Continuous data were analyzed by two-way repeated-measure analysis of variance using group as the independent samples factor and time as the repeated measurement factor. A P value less than 0.05 (a = 0.05) was considered statistically significant. Data were analyzed using SPSS statistical software version 13.0. (SPSS Inc, Chicago, IL, USA).


  Results Top


A total of 60 patients underwent elective cholecystectomy for cholelithiasis (60%), ureterolithotomy, pyelolithotomy, and pyeloplasty under general anesthesia: 30 patients with continuous infusion (group I) and 30 with intermittent bolus rocuronium (group II) were included in the current study. The patients in the present study of ASA 1 and 11 were comparable in age, weight, and sex, and all surgical interventions were completed successfully in all enrolled patients [Table 1].
Table 1 Demographic data of the study patients

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The mean heart rate and mean arterial pressure at different time intervals after intubation with rocuronium were not significantly different (P>0.05) between the groups [Table 2] and [Table 3].
Table 2 Mean heart rate at different time intervals of the study groups

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Table 3 Mean arterial pressure at different time intervals of the study groups

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In terms of the degree of clinical relaxation, 28 patients in group I at 15 min showed better clinical relaxation (i.e. grade 4) compared with 17 patients in group II. Similarly, at subsequent time intervals, more patients in group I showed better clinical relaxation compared with group II. Thus, the continuous infusion group showed more uniform clinical relaxation than the intermittent bolus group [Table 4] and [Figure 1].
Figure 1: Intraoperative clinical relaxation grading of the study groups. The X axis represents the duration of surgery and the Y axis represents the median value of the grade of clinical relaxation

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Table 4 Clinical relaxation at different time intervals of the study groups

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The average drug requirement calculated in mg/kg/min was significantly greater in group II compared with group I (7.9 vs. 7 mg/kg/min, respectively) [Table 5]. Recovery scores after reversal were 4.46 ± 0.47 (4) at 5 min to 6.9 ± 0.50 (7) at 20 min in the continuous infusion group and 2.56 ± 0.80 (3) at 5 min to 6.03 ± 0.63 (6) at 20 min in the intermittent bolus dosing group. On comparing both groups, statistically significant better quality of recovery status was observed in the continuous infusion group [Table 6].
Table 5 Total drug requirement throughout the study period

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Table 6 Patients ' recovery status (with the modifi ed steward score) in the study groups

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  Discussion Top


The administration of neuromuscular blocking drugs by a continuous infusion provides greater stability of drug concentration and ensures greater consistency in the degree of paralysis. When appropriately titrated to individual patient requirements, infusion techniques may potentially help avoid periods of both inadequate and excessive drug effects and may actually decrease the total drug requirement while facilitating rapid reversal following administration of an appropriate antagonist immediately within a short period of termination of infusion.

The present study was carried out using rocuronium bromide to determine clinically, with grading and scoring systems, namely the clinical relaxation grading system and the modified steward score without a nerve stimulator, whether the continuous infusion or the intermittent bolus dosing of rocuronium bromide yielded better clinical conditions for an operation. Also, intraoperative hemodynamic status, total drug requirement, and recovery status were compared between the two groups.

Rocuronium bromide as a continuous infusion was started at 0.5 mg/kg/h with a 0.5 mg/ml concentration in 30 patients in group I and an intermittent bolus dosing of 0.15 mg/kg in another 30 patients in group II following an intubating bolus dose of 0.9 mg/kg in both groups. Infusion was started at 5 min following an intubating bolus dose and was stopped at the beginning of skin suture. Tempia et al. [7] used a continuous infusion immediately following the initial bolus dose. King et al. [8] used an infusion 5 min after the incision; McCoy et al. [9] commenced infusion depending on nerve stimulator finding at recovery of T 1 to 10% of control. Onset time and recovery of T 1 to 10% were 72 ± 19.9 s and 27 ± 9.6 min, respectively. We preferred an infusion at 5 min following a bolus dose as there was an increase in the incidence of sudden recovery from block when the infusion was started late.

Intraoperative heart rate and mean arterial pressure were recorded at 15 min intervals and the first recording was performed 5 min after intubation. Five minutes after intubation, there was an increase in the mean heart rate in groups I and II to 111 ± 8.68 and 116 ± 6.75 from the baseline value of 85 ± 5.23 and 84 ± 4.8, respectively. Similarly, the mean arterial pressures 5 min after intubation increased to 96.04 ± 4.25 and 97 ± 6.28 from the baseline value of 93.12 ± 5.7 and 94.11 ± 4.422, respectively. In the present study, there were insignificant (P > 0.05) steady-state variations in heart rate and mean arterial pressure at different time intervals after intubation with rocuronium in both groups, which is consistent with several studies [10],[11],[12],[13],[14],[15] . This initial increase in hemodynamic was probably because of laryngoscopy and intubation. After about 15-20 min, in both groups, the hemodynamic was stable, with no significant intergroup variation.

In the present study, clinical relaxation was assessed by a grading technique at 15 min intervals intraoperatively and it was found that there was more uniform grading in group I compared with group II. Also, it was found that more number of patients achieved better clinical relaxation in the continuous infusion group (P < 0.05). Use of an infusion shortened the time of attaining steady-state relaxation. Infusion required some adjustment in the beginning because of inadequate neuromuscular block. It was also observed that intermittent bolus doses had to be administered early with infusion in a few patients, but these patients were excluded from the study. The apparently lower requirement of rocuronium from around 80 to 90 min onwards may be because of accumulation of the drug. King et al. [8] used a grading system on the basis of surgical field condition for the assessment of the quality of neuromuscular block. Similarly, we formulated the grading system on the basis of clinical manifestation and its correlation to nerve stimulator findings from standard textbooks [16],[17] .

The average total drug requirements per kilogram per minute were evaluated from patients. Here, it was observed that the average drug requirement in the continuous infusion group was 7 mg/kg/min compared with the intermittent bolus dosing of 7.9 mg/kg/min (it was evaluated as mg/kg/min in the intermittent group for easy comparisons), which was significantly lower in group I compared with group II. Observations were compared with Shanks et al. [18] and MacCoy et al. [19] ; the values were 10 and 9.5 mg/kg/min for continuous infusion, with relaxation maintained at 95 and 90% depression of T 1 , respectively. The apparently lower requirement of drug in our study group may be because of the imperfect degree of neuromuscular block that was assessed clinically without a peripheral nerve stimulator. Pharmacokinetics and pharmacodynamics of rocuronium might be altered by physical and disease status, and occupational and geographical variations of patients. Its effect prolong in liver disease, renal disease, prolonged circulation time and also on technique of anesthesia.

Recovery status in two groups was compared by the steward score, which was modified by adding one more score of head raising and sustained for more than 5 s. On assessing the recovery status 5 min after administering neostigmine till 20 min, it was found that the continuous infusion group showed significantly (P < 0.05) better quality of recovery status. Complete recovery was attained within 20 min of administering neostigmine in the two groups, with a better score in group I. We modified the Steward score to use it as a general anesthesia recovery score. Wadhawan et al. [20] and Chhabra et al. [21] used this score to assess recovery from general anesthesia. Therefore, a scoring system may also be effective instead of a nerve stimulator to assess the status of recovery from anesthesia.


  Conclusion Top


Rocuronium infusion offers a better and stable degree of relaxation compared to intermittent bolus dosing for intermediate duration of operation, which can be assessed using a clinical relaxation grading system. Rocuronium is a rapidly acting and hemodynamically stable non-depolarizing muscle relaxant with fewer drug requirements and better quality of recovery status during continuous infusion.

Acknowledgements

The authors thank their exhead of the Department, Professor Dr. A. K. Deka, Department of Anaesthesiology and Critical Care, Gauhati Medical College and Hospital, Guwahati, for his encouragement and help in completing this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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