https://doi.org/10.5812/aapm.18488

The Effect of Defasciculating Doses of Pancuronium and Atracurium on Succinylcholine Neuromuscular Blockade

authors:

avatar Cyrus Motamed 1 , * , avatar Duvaldestin Philippe 2

Department of Anesthesia, Gustave Roussy Institute, Rue Camille Desmoulins 94080 Villejuif, France University of Paris 11, Paris, France
Department of Anesthesia, Hospital Henri Mondor, Avenue de Lattre de Tassigny 94010 Créteil, France University of Paris 12, Paris, France
Anesthesiology and Pain Medicine: Vol.4, issue 4; e18488
published online: September 2, 2014
article type: Brief Report
received: February 24, 2014
revised: April 7, 2014
accepted: April 28, 2014

how to cite: Motamed C, Philippe D. The Effect of Defasciculating Doses of Pancuronium and Atracurium on Succinylcholine Neuromuscular Blockade. Anesth Pain Med. 2014;4(4):e18488. https://doi.org/10.5812/aapm.18488.

Abstract

Background:

A defasciculating dose of non-depolarizing muscle relaxant administered prior succinylcholine decrease its side effects including fasciculations and postoperative myalgias; however it is believed that the dosage of succinylcholine should be increased when such a pre-treatment is used.

Objectives:

We hypothesized that a defasciculating dose of pancuronium as a pre-treatment could prolong its duration of effect.

Patients and Methods:

Forty patients scheduled for elective orthopaedic surgery were consecutively assigned into 5 groups, a first group without pre-treatment (succinylcholine 1 mg/kg) and 4 subsequent groups of pretreatment with atracurium 0.05 mg/kg + succinylcholine 1 or 1.5 mg/kg and pancuronium 7.5 µg /kg + succinylcholine 1 and 1.5 mg/kg. The muscle relaxant effect of succinylcholine was assessed with a force transducer using train of four stimulations every 12 seconds. Kruskall Wallis Anova test was used to compare results.

Results:

The duration of succinylcholine induced paralysis (1 and 1.5 mg/kg) was significantly prolonged with pre-treatment with pancuronium but succinylcholine 1mg/kg did not reached maximum blockade after pre-treatment with atracurium. After pancuronium, full recovery after succinylcholine 1.5 and 1 mg/kg occurred respectively after 18 and 15 minutes. P < 0.05 vs. 12 minutes for succinylcholine 1mg/kg alone.

Conclusions:

This study highlights potentiation effect of a defasciculating dose of pancuronium on succinylcholine paralysis suggesting the lack of justification to increase succinylcholine dosage.

1. Background

Succinylcholine is used mainly used to facilitate tracheal intubation in emergency procedures but also in elective surgery, however because of multiple side effects including fasciculations muscle damage and late postoperative myalgia, a small dose of non-depolarising muscle relaxants (NDMR) may be used to decrease these side effects (1-6). Nearly all of NMDR might be used (7, 8), however magnesium sulphate is also reported to be efficient for this purpose (9). In addition, it’s generally believed that the dose of Succinylcholine should be enhanced because of receptor competition with the NMDR (10-13).

2. Objectives

A defasciculating dose of Pancuronium might have different pharmacokinetic profile, because of serum anticholinesterase activity (14, 15). In previous works we investigated different effect of low dose of pancuronium on mivacurium pharmacodynamics, suggesting that the potentiation of mivacurium effect would mostly be the result of the anti-cholinesterase activity of a low dose of pancuronium although a receptors competitive action cannot be totally excluded (16-18). Succinylcholine, like mivacurium is eliminated by plasma cholinesterase (BChe) (19, 20), therefore we hypothesized the same pharmacokinetic effect of low dose of pancuronium (18) could enhance the duration of neuromuscular blockade of succinylcholine.

4. Results

The mean age of patients was of 59 ± 12 year with a mean weight of 75 ± 23 kg and the mean height 167 ± 11 cm, no statistical difference was found between groups in demographic characteristics. No side effects occurred after the injection of pancuronium or atracurium.

Maximum blockade reached 100% except in Atra sux 1 group (95%).

The mean duration of Succinylcholine neuromuscular blockade (1mg/kg and 1,5 mg/kg) was significantly prolonged when it was preceded by administration of low dose pancuronium and shortened when preceded by low dose atracurium in comparison with Succinylcholine 1mg/kg alone (P < 0.05) (Table 1).

Table 1.

Neuromuscular Characteristics of Different Combinations

E Max a, %T 70 b, MinT 90 b, MinT 100 b, MinSignificance
Atra sux 1954.8 (3.3-7.4)6.0 (4-8.5)7.1 (4.8-9)P < 0.05 vs sux 1
Panc sux 110012.2 (7-21.5)14.3 (8.8-23.7)15.8 (11.3-26)P < 0.05 vs sux1
Sux 11009.1 (5.8-13.2)11.5 (6.8-15.7)12.4 (9.1-16.9)-
Panc sux 1.510013.3 (8.2-20.8)15.8 (10.7-24.1)18.2 (12.5-28.7)P < 0.05 vs sux 1
Atra sux 1.51008.6 (4.7-12.3)10.4 (5.8-10.5)12.6 (7.2-16)P < 0.05 vs panc sux 1.5

5. Discussion

This study shows that low dose of pancuronium prolongs the duration of action of Succinylcholine induced paralysis whereas atracurium reduces it, therefore increasing the dose of succinylcholine is not necessary in case of pancuronium pre-treatment. Traditionally the administration of a very low dose of NDMR is used to prevent succinylcholine induced side effects (mostly fasciculations and post-operative myalgias) (21), however the dose of sucinylcholine should be increased to obtain satisfactory neuromuscular paralysis and or intubation conditions described in several investigations (10, 12, 22) this was demonstrated also in the present study with atracurium followed by succinylcholine 1mg/kg since the maximum neuromuscular effect was of 95% in comparison to other combinations or alone. Nevertheless, despite multiple studies considering side effects of pre-treatment very few investigated the duration of induced paralysis after such combinations.

As previously described with mivacurium, the potentiation of succinylcholine by pancuronium might be explained by the reduced hydrolysis of succinylcholine due to Bche inhibition (18). Although clear relationship between a decrease in Bche and a prolongation of effect of mivacurium could not be demonstrated (18).

We used the higher dose of pancuronium suggested for pre-treatment (21) to fulfill the purpose of the study in order to yield a decrease in cholinesterase activity, however our timing of the propofol injection (2 minutes after injection of low dose of pancuronium or atracurium), avoided the occurrence of side effects including blurred vision, diplopia, heavy eyelids, weakness, difficulty in breathing and swallowing or desaturation.

This investigation was open labelled, and not randomized since our primary endpoint was objective assessment of dose-effect relationship in clinical practice, we also did not measured the Bche after administration of pancuronium but in accordance to our previous dose-response investigations with intubating and maintenance doses we assumed Bche would significantly decrease despite remaining within clinical range (18). In addition the sample size was not chosen to evaluate the side effect of succinylcholine but only to prove an increase in the duration of paralysis. This study confirms the result of a previous investigation using higher dose of NDMR for pre-treatment (17).

Low dose of NDMR before succinylcholine is considered to be safe provided accurate dosing and timing however we suggest to consider also the type of NDMR as pancuronium enhances the effect of succinylcholine and atracurium reduces it, therefore increasing the dose of succinylcholine is not justified when pancuronium is used as a pre-treatment.

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