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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 1  |  Issue : 1  |  Page : 17-21

Evaluation of the effect of saline flush on the time of onset and duration of action following bolus dose of rocuronium


Department of Anaesthesiology and Intensive Care, Maulana Azad Medical College, New Delhi, India

Date of Submission18-Oct-2021
Date of Acceptance03-Apr-2022
Date of Web Publication20-May-2022

Correspondence Address:
Dr. Vineet Manchanda
House No. 1 1st Floor Old Market Ramesh Nagar, New Delhi - 110 015
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jica.jica_3_21

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  Abstract 

Background: Circulatory factors modify the onset time of neuromuscular-blocking drugs. Therefore, we hypothesized that a bolus of saline flush immediately after rocuronium administration would shorten the onset time without influencing the duration of the rocuronium effect. Methods: A total of 84 patients were randomly allocated to either the control or saline flush group. Anesthesia was induced with propofol and fentanyl and maintained with isoflurane <1% and all patients received 0.6 mg/kg rocuronium in 10 mL of normal saline. In the saline flush group, 20 mL normal saline was immediately infused after rocuronium administration. Neuromuscular blockade was assessed using TOF-WATCH device at the adductor pollicis muscle using stimulation of ulnar nerve. The neuromuscular indices recorded were latent onset time, onset time, and clinical duration of bolus dose of rocuronium. Results: The measured latent onset time and onset time were significantly shorter within the saline flush group than the control group (P < 0.001). In addition, the clinical duration was significantly prolonged within the saline flush group (P < 0.001). Conclusion: A 20-mL saline flush administered immediately after slow intravenous 0.6 mg/kg rocuronium shortens the onset time and prolongs the clinical duration of neuromuscular blockade.

Keywords: Neuromuscular blockade, onset time, rocuronium


How to cite this article:
Manchanda V, Saxena KN, Wadhwa B. Evaluation of the effect of saline flush on the time of onset and duration of action following bolus dose of rocuronium. J Ind Coll Anesth 2022;1:17-21

How to cite this URL:
Manchanda V, Saxena KN, Wadhwa B. Evaluation of the effect of saline flush on the time of onset and duration of action following bolus dose of rocuronium. J Ind Coll Anesth [serial online] 2022 [cited 2022 Sep 28];1:17-21. Available from: https://www.jicajournal.in//text.asp?2022/1/1/17/345597


  Introduction Top


An early onset of action of neuromuscular blocking drugs is desirable in patients who require rapid sequence induction (RSI) of anesthesia. While succinylcholine was once considered to be an ideal muscle relaxant to facilitate endotracheal intubation during induction of anesthesia, its use is limited by severe hyperkalemia, arrhythmias, severe bradycardia after the second dose, increase in intracranial pressure, intragastric pressure, intraocular pressure, and postoperative myalgia.[1],[2],[3]

The onset of drug action depends on the drug distribution kinetics such as circulatory mixing and transit time, which is the time taken by the drug to reach target site from peripheral injection site.[4],[5] Intravenous drug injection into peripheral vein followed by administration of a fluid bolus has been shown to be comparable to direct administration into the right atrium. This technique has previously been used to reduce the onset of action of nondepolarizing muscle relaxant (NDMR) by Nitahara et al.[5] In a dose of 1.2 mg/kg, rocuronium has rapid onset of action within 60 sec, longer duration of action, and excellent intubating conditions.[6] Ishigaki et al. demonstrated that saline flush after a dose of 0.6 mg/kg rocuronium not only reduced the onset time to muscle relaxation but also prolonged the duration of action. However, there is a paucity of studies in literature regarding the effect of saline bolus after administration of rocuronium, with only one study demonstrating prolongation of duration of action of drug.[7] Hence, their study was designed to evaluate the effect of saline flush after rocuronium bolus on onset time and duration of effect of drug and on intubating conditions.


  Methods Top


After institutional ethics committee approval, this prospective, randomized, controlled study was carried out over a period of 1 year from May 2019 to May 2020.

Patients of the American Society of Anesthesiologists Grade I to II aged 18–65 years with body mass index ≤30 kg/m2 who were scheduled for elective surgeries under general anesthesia with intubation were included in the study. Patients with preexisting neurological, neuromuscular disorders, cardiovascular disease, known liver and kidney disease, contraindication, or previous adverse response to any of the study drugs, who were on any drugs known to interfere with the metabolism of NDMR, and those with documented electrolyte disorders were excluded from the study.

Written informed consent for participation in the study was obtained from eligible patients. The primary outcome of the study was the effect of saline flush versus no saline flush on the time of onset of muscle relaxation. The secondary outcomes were the effect of saline flush versus no saline flush on the duration of action of bolus dose of rocuronium and endotracheal intubation condition provided.

The sample size for the study was calculated as following:

Patients per group (N) = (σ12 + σ22) (Z1-α/2 + Z1-β)2/(M1– M2)2 = (8.32 + 9.42)(1.96 + 0.84)2/(31.5-37)2 = 42

Where, σ1 = Standard deviation of the control group (8.3).

σ2 = Standard deviation of the test group (9.4).

Z1-α/2 = For 5% significance is 1.96.

Z1-β = For power of study 80% is 0.84.

M1 = Mean of the control group (31.5).

M2 = Mean of the test group (37).

Hence, a total of 84 patients were recruited for participation in the study [Figure 1].
Figure 1: CONSORT 2010 Flow Diagram. Group 1: Rocuronium, Group 2: Rocuronium with saline flush

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Preanesthetic checkup of patients was conducted as per our institutional policy. For surgery, patients were instructed standard fasting period and tablet alprazolam 0.25 mg on the night prior and morning of surgery was given. On the day of surgery, patients were randomly allocated into one of the two study groups using computer-generated random table. The allocation of patients was concealed in sealed white opaque envelopes. In the control group (Group 1), no saline bolus was administered after intravenous rocuronium, whereas patients in the study group (Group 2) received 20 ml of intravenous saline after administration of rocuronium.

After moving the patient into the operation theater, the standard anesthesia monitors were attached, i.e., continuous electrocardiogram (E.C.G), pulse oximetry, noninvasive blood pressure, and surface temperature probe. An intravenous cannula (IV) of 18G (Gauge) was secured on the dorsum of nondominant hand of patient and intravenous fluid infusion was started. For monitoring of neuromuscular blockade, ulnar nerve and adductor pollicis muscle in the upper arm contralateral to the IV arm were selected. Train of four (TOF) was selected for monitoring NM blockade using a portable handheld TOF-Watch device.

Before induction of anesthesia, the patient was preoxygenated for 3 min followed by IV administration of fentanyl 2.0 μg/kg lean body weight (LBW) calculated from the following formula;

  • Male: 1.1 × TBW − 128× (TBW ÷ Height)2
  • Female: 1.07 × TBW– 148× (TBW ÷ Height)2


Induction of anesthesia was accomplished with injection propofol up to titrated to loss of verbal response. The patient's lungs were ventilated with mixture of oxygen (O2) and nitrous oxide (N2O) in 1% isoflurane. Neuromuscular monitoring was started immediately after induction of anesthesia, before administration of neuromuscular blocking drug. The ulnar nerve was stimulated at the wrist using TOF-Watch monitor. The transducer was placed on volar aspect of the thumb using hand adapter and contraction of adductor pollicis muscle was measured. Additional top-up of propofol was permitted as necessary during calibration of the TOF-Watch device.

After checking the ability to mask ventilate, intubation was facilitated by administration of 0.6 mg/kg LBW rocuronium in 10 ml of normal saline injected over 5 s. Following administration of rocuronium, as per group allocation, Group 1 received no saline flush and Group 2 received 20 ml saline flush over 5 s through 3-way stopcock connected to the IV cannula. The latent onset time and onset time of muscle relaxant as guided by the neuromuscular monitoring were noted. The latent time of onset of muscle relaxant was the time from the administration of rocuronium bolus until the first occurrence of T1 depression of TOF >5% was noted and the onset time was defined the time from the administration of rocuronium bolus to the time when TOF reaches zero. Following this, the jaw tone was assessed and direct laryngoscopy followed by tracheal intubation with endotracheal tube. Endotracheal tube sizes were standardized to 7–7.5 mm internal diameter (ID) for female and 8–8.5 mm ID for male patients. The ease of intubation was assessed by intubation difficulty scale and included the jaw tone, position, and movement of vocal cords during laryngoscopy and coughing and bucking following intubation[8] [Annexure 1]. After successful intubation, controlled ventilation was established with target end-tidal CO2 32–36 mmHg and anesthesia was maintained with a gaseous mixture of O2 and N2O (33:67) in 0.6% isoflurane 0.6%. TOF monitoring for neuromuscular blockade was continued throughout the surgical procedure. The total duration of action of drug administered for facilitating endotracheal intubation was noted. Duration of bolus dose of muscle relaxant was defined as time from TOF zero to appearance of first twitch on TOF-Watch device and was noted for both the groups.



For statistical analysis, qualitative variables such as intubating conditions were presented in terms of frequency percentage (%) and statistical significance between the two groups was compared using Chi-square test/Fisher's exact test.

The quantitative variables such as latent time of onset, time of onset, and duration of action of bolus dose were presented in terms of range, mean, and standard deviation. Statistical significance was determined using Student's “t”-test.

The nonnormally distributed continuous variables were presented in terms of median (interquartile range), and statistical significance was determined using nonparametric Wilcoxon rank-sum test. The level of statistical significance was taken as a0.05. The data were analyzed using Statistical Package for the Social Sciences (SPSS) standard software version 17.0.


  Results Top


A total of 84 patients were enrolled for the participation and there was no dropout; all patients completed the study. The demographic characteristics including age, height, and lean body weight were comparable in both the groups [Table 1]. The mean latent onset time was 56.02 ± 15.57 s in Group 1, whereas it was 38.88 ± 11.47 s in Group 2. The difference between the groups was found to be statistically significant with P < 0.001. The mean onset time of muscle relaxant was found to be significantly longer (P < 0.001) in the control group. The mean time of onset was 4.20 ± 2.29 min in Group 1 as compared to 2.70 ± 1.37 min in Group 2. The clinical duration was found to be 14.92 ± 4.23 min in Group 1 as compared to 21.34 ± 4.28 min in Group 2. The difference in the clinical duration of drugs was also observed to statistically different (P < 0.001) [Table 2]. On comparison of intubating conditions, it was found to be significantly better (P = 0.02) in Group 2 as compared to Group 1 at TOF zero. The total score for intubating conditions was found to be 11.45 ± 0.67 in Group 1 as compared to 11.86 ± 0.47 in Group 2 [Table 3].
Table 1: Demographic characteristics

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Table 2: Mean latent onset time, mean onset time, and mean clinical duration

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Table 3: Score for intubating conditions

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  Discussion Top


Rocuronium is a NDMR which when used in higher doses can shorten the onset time; however, it can also considerably prolong the duration of action.[9],[10],[11] To accelerate the onset time of rocuronium-induced neuromuscular blockade, various pharmacological or nonpharmacological techniques have been used in clinical practice,[12],[13] such as arm elevation, riming principle, and saline flush.

Saline flush has been used to reduce the onset time as it decreases the time of drug delivery from the peripheral injection site to the effector site. This technique has been used in various procedures such as dye injection in contrast-enhanced computed tomography and to reduce the onset time of injection adenosine and ephedrine. Recently, saline flush has been used to reduce the onset time of rocuronium.

In our study, we evaluated the effect of bolus injection of saline on the onset time, latent onset time, and clinical duration of bolus dose of rocuronium and intubating conditions.

Our study showed that bolus injection of saline caused more rapid drug delivery to the central circulation and hence shortened the onset time of rocuronium. The onset time and latent onset time were found to be significantly lesser in the saline flush group as compared to the nonsaline flush group.

Intubating conditions were assessed clinically by 4 parameters of jaw tone, vocal cord position, vocal cord movement, and coughing during intubation. In this scoring, each intubation score was assigned a numeric value in increasing order that signifies increasing quality of intubating conditions. Intubating conditions were found to be significantly better in the saline flush group as compared to the nonsaline flush group at TOF value zero.

The clinical duration was found to be significantly higher in the saline flush group as compared to the nonsaline flush group, which was a new finding reported by Ishigaki et al. also.[7] They reasoned that saline flush shortened the drug transit time to the central circulation and also may have increased the peak rocuronium concentration. This may have decreased the variance in transit time distribution at the effect site. A higher peak plasma concentration at the effect site can prolong the recovery phase.[8] Thus, saline flush appeared to be a very useful technique as we were able to reduce the onset time of rocuronium without increasing the dose. However, there was also an increase in the total duration of action and this happened to be the lacunae in our study as we did not study the reversal characteristics. Thus, this parameter requires further evaluation.

Our study compared the onset time, latent onset time, clinical duration, and ease of intubation between the group receiving bolus injection of 0.6 mg/Kg rocuronium (Group 1) and the group receiving bolus injection of 0.6 mg/kg rocuronium followed by 20 ml saline flush (Group 2). It was found that the group receiving 20 ml saline bolus following rocuronium had a shorter latent onset time, shorter onset time, prolonged clinical duration of action of bolus dose of rocuronium, and improved intubating conditions. This method is free from side effects associated with methods such as priming principle.

Thus, we recommend a lesser dose (0.6 mg/kg) of rocuronium with 20 ml of saline flush for achieving adequate intubating conditions at faster onset time so that RSI and intubation can be accomplished using rocuronium in conditions where the use of succinylcholine is contraindicated or questionable.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
El-Orbany M, Connolly LA. Rapid sequence induction and intubation: Current controversy. Anesth Analg 2010;110:1318-25.  Back to cited text no. 1
    
2.
Kararmaz A, Kaya S, Turhanoglu S, Ozyilmaz MA. Effects of high-dose propofol on succinylcholine-induced fasciculations and myalgia. Acta Anaesthesiol Scand 2003;47:180-4.  Back to cited text no. 2
    
3.
Levine M, Brown DF. Succinylcholine-induced hyperkalemia in a patient with multiple sclerosis. J Emerg Med 2012;43:279-82.  Back to cited text no. 3
    
4.
Weiss M, Reekers M, Vuyk J, Boer F. Circulatory model of vascular and interstitial distribution kinetics of rocuronium: A population analysis in patients. J Pharmacokinet Pharmacodyn 2011;38:165-78.  Back to cited text no. 4
    
5.
Nitahara K, Sugi Y, Shigematsu K, Kusumoto G, Abe S, Higa K. Effect of bolus injection of 20 ml saline with arm elevation on the onset time of vecuronium administered via a peripheral vein: A randomised controlled trial. Anaesthesia 2013;68:904-7.  Back to cited text no. 5
    
6.
Sørensen MK, Bretlau C, Gätke MR, Sørensen AM, Rasmussen LS. Rapid sequence induction and intubation with rocuronium-sugammadex compared with succinylcholine: A randomized trial. Br J Anaesth 2012;108:682-9.  Back to cited text no. 6
    
7.
Ishigaki S, Masui K, Kazama T. Saline flush after rocuronium bolus reduces onset time and prolongs duration of effect: A randomized clinical trial. Anesth Analg 2016;122:706-11.  Back to cited text no. 7
    
8.
Adnet F, Borron SW, Racine SX, Clemessy JL, Fournier JL, Plaisance P, et al. The intubation difficulty scale (IDS): Proposal and evaluation of a new score characterizing the complexity of endotracheal intubation. Anesthesiology 1997;87:1290-7.  Back to cited text no. 8
    
9.
Martin R, Carrier J, Pirlet M, Claprood Y, Tétrault JP. Rocuronium is the best non-depolarizing relaxant to prevent succinylcholine fasciculations and myalgia. Can J Anaesth 1998;45:521-5.  Back to cited text no. 9
    
10.
Han T, Kim H, Bae J, Kim K, Martyn JA. Neuromuscular pharmacodynamics of rocuronium in patients with major burns. Anesth Analg 2004;99:386-92.  Back to cited text no. 10
    
11.
Wierda JM, Hommes FD, Nap HJ, van den Broek L. Time course of action and intubating conditions following vecuronium, rocuronium and mivacurium. Anaesthesia 1995;50:393-6.  Back to cited text no. 11
    
12.
Foldes FF. Fine tuning the priming principle. Anesthesiology 1985;63:560-1.  Back to cited text no. 12
    
13.
Koh KF, Chen FG. Rapid tracheal intubation with atracurium: The timing principle. Can J Anaesth 1994;41:688-93.  Back to cited text no. 13
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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