Incidence And Severity Of Suxamethonium Induced Fasciculation And Post-Operative Myalgia, And Their Association With Different Iv Induction Agents Among Adult Patients Underwent Elective Surgery At Jimma Medical Center, A Prospective Cohort Study

Keywords

Suxamethonium Induced Fasciculation; Post-Operative Myalgia; Incidence, Severity; IV Induction Agents; JMC, Ethiopia.

Introduction

Despite suxamethonium started to be used as one of the anesthetic drugs for muscle relaxation with extra short onset of action and brief duration of action since 1949, it was also accompanied with different side effects [1, 2]. One of the profound side effect is neuromuscular effects and muscle pain that patients experienced at post-operative period probably due to intraoperative fasciculation discerned or secondary to damage produced in the muscle during fasciculation [3-6]. The possible mechanism of SIF is due to prejunctional depolarizing action of succinylcholine, resulting in repetitive firing of the motor nerve terminals and antidromic discharges that manifest as uncoordinated muscle contractions [7]. The phenomenon of POM was first noted in 1952 by Churchill- Davidson following injections of succinylcholine due to diffuse uncoordinated contractions of muscle bundles [8]. POM refers to occasional vigor of muscle contractionsthat may give rise to a feeling of muscular stiffness/ pain of (facial, jaw, neck, shoulder, chest, back, trunk, limb/extremities)after consciousness has been regained. It commonly manifested as the pain one might suffer after strenuous physical exercise and usually affecting more than one site that causing disability or limiting activities and difficulty on getting out of bed or turning head postoperatively [9, 10]. It is postulated due to increased intracellular calcium concentrations, membrane phospholipid degradation, and release of free fatty acids or free radicals, which lead to increased membrane permeability [11-13].

The incidence of POM is significant and varies among patients underwent surgery with succinylcholine. The duration of discomfort is also highly variable among patients but, it usually appears on the first day after surgery and lasts for 2 or 3 days, occasionally persists for as long as a week [14-16]. POM is revealed as source of distress to patients than surgical site wound for its unpleasant consequences to patients’ quality of life (delayshospital admission period, expose to unplanned expenses, prolongs time to return to daily activity and influence individual’s productivity) [17, 18]. The incidence of POM also varies among IV induction agents (minimal among propofol [19, 20]) and interventional studies reported that its incidence was minimized by pretreatment of atracurium [21], rocuronium [22], vecuronium [23] diclofenac [24], ketorolac [25],phenytoin [26], lidocaine [27], benzodiazepines [28], calcium gluconate [29] and magnesium sulfate [30].

Despite, the applicability of ideal muscle relaxants that used instead of suxamethonium in developed countries for their minimal side effects; it is the only available and utilized short acting muscle relaxant in the setting and considering that the incidence of fasciculation and POM are inevitable. Thus, the present study was aimed to sort/opt for the possible IV induction agent/s that has/ have minor side effects (SIF and POM) because it is the standard to prevent/reduce fasciculation and POM.

Materials and Methods

The study was conducted among a total of 140 patients underwent elective surgeryby four IV induction agents (propofol, thiopentone, ketamine and ketofol) from August 1-September 30, 2019 at JMC. JMC islocated at Jimma zone, Oromia region at distance of 350 km to southwest from the capital of Ethiopia, Addis Ababa.Itis one of the pioneer teaching referral hospitals of the country serving millions of population in the catchment area. A prospective cohort study design was employed to assess POM and SIF after all patients were equally exposed to different four induction agents (propofol, thiopentone, ketamine and ketofol) 35 patients in each groupaimed to sort for the possible induction agent/s that has/have minor side effects.

SIF was assessed intraoperatively following sux administration by structured questionnaire for grading and scoring of fasciculation [31, 32] and operationalized as:

 Fasciculation: refers to any involuntary contraction/tremor of skeletal muscles discerned immediately following administration of sux.
 Grade 0 fasciculation (Nil): No visible fasciculation  Grade 1(mild): Fine fasciculation of the eyes, face, neck, fingers without movement of limbs
 Grade 2(moderate): Fasciculation of greater intensity at more than two sites or movement of
 Limbs (fasciculation involving limbs and/or trunk).
 Grade 3(severe): Vigorous sustained and widespread fasciculation or fasciculations with movement of one or more limbs and/ or movements requiring forceful retention.
POM was assessed postoperatively at 24hrs by structured tools (Postoperative Myalgia Survey (PMS) with 14-item and Postoperative Myalgia Evaluation Scale (PMES which is a modification of the Visual Analog Pain Scale (VAPS) with 4-Likert scale /0-3) [33,34]and operationalized as:
 POM: refers generalized aches/sores/stiffness/pains of muscles that commonly occur within 24 hours after surgery.
 Nil: No muscle pain or stiffness
 Mild myalgia: Slight pain at one site but not causing disability.
 Moderate myalgia: Pain at more than one site but not causing disability
 Severe myalgia: Pain at more than one site, causing disability in turning head and standing-up.

The data was entered into Epidata version 4.3.1 and finally exported to SPSS version 20 for further analysis. Both descriptive statistics and analytical statistics were applied and the finding was reported bytables/figures and narration.Binary logistic regression was usedto assess the association ofoutcome variable (POM) with fasciculation and IV induction agents. P value < 0.05 was considered as statistically significant. The study was approved by ethical review board of Jimma University and letter of permission/cooperation was collected from school anesthesia and the hospital.

After the purposes of the study was explained to patients who underwent elective surgery, both verbal and written consent were taken from volunteer participants.Informationgathered from respondents waskept confidential.

Results

Baseline characteristics of patients underwent elective surgery

A total of 140 participants were enrolled to the study with the mean age of 36.5 +10.5 that ranged from 18-60 years, with male to female ratio of 1:2.18. Respondents were exposed to four IV inductions agents (each 35) intraoperatively and all relaxed by suxamethoniumas detailed in Table 1.

Incidence of sux induced fasciculation and its severity

The incidence of fasciculation at intraoperative period following the administration of sux was 94.3% in general where it varies among induction agents (higher among patients induced with thiopentone34 (24.3%)and lower among propofol group 32 (22.9%). As severity of SIF was assessed by grading and scoring tool of fasciculation, majority of them were allocated to moderate 54(38.3%) scale. Among total of 41 patients with mild fasciculation, majority was seen among patients induced by ketamine 15(10.7%) where the rest mild SIF was observed among thiopentone 11(7.9%), ketofol 8(5.7%) and propofol 7(5.0%). Moderate SIF was also dominantly observed among patients induced by propofol and ketamine (each 15(10.7%)). But, severe scale of SIF was higher among patients induced by thiopentone 13(9.3%) followed by ketofol 11(7.9%), propofol 10(7.1%) and ketamine 3(2.1%) as seen on (Table 2).

Incidence of POM and its severity

The incidence of POM at 24 hours of post-operative period was 29.3% that complained for muscle pain/stiffness among 41 patients where the higher magnitude screened among patients induced by ketamine 15(10.7%), followed by thiopentone and ketofol (each 10 (7.1%)) while minimal among propofol group 6(4.3%. POM was also further allocated to mild 30(21.4%), moderate 10(7.1%) and severe scale 1(0.7%). Severe scale of POM was only observed among patients induced by thiopentone (Table 3).

Association of POM with IV induction agents

The association of POM with IV induction agents was performed by logistic regression. Despite, non-statistically significant difference, the occurrence of POM was varied among IV induction agents. The likelihood of POM occurrence was more likely among patients induced by ketamine [OR 1.8(0.7-5.1), p=0.215)] and thiopentone [OR 1.1(0.3-2.8), p=0.999)] but less likely among patients induced by propofol [OR 0.5(0.1-1.6), p=0.259)] by taking patients induced by ketofol as referenceas detailed in Table 4.

Association of SIF with IV induction agents

The likelihood of SIF occurrence was also varies among IV induction agent(about two fold among thiopentone groups [OR 2.1(1.2-23), p=0.563]), but not showed statistically significant difference among groups (Table 5).

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Table 1:

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Table 1. Demographic and operative characteristics.

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Table 2:

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Table 2. Intraoperative exposure variables in elective surgical patients under general anesthesia.

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Table 3:

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Table 3. The side effects of study drugs in elective surgical patients under general anesthesia.

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Table 4:

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Table 4. The side effects of study drugs in elective surgical patients under general anesthesia.

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Table 5:

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Table 5. The side effects of study drugs in elective surgical patients under general anesthesia.

Discussions

A total of 140 respondents wereenrolled to the study with the mean age of 36.5+10.5 that ranged from 18– 60 years who equally exposed to four IV inductions agents(each 35) intra-operatively and intended to assess POM within 24 hours of post-operative period by applying prospective cohort study design.

The incidence of fasciculation at intraoperative period following the administration of sux was 94.3% and it varies among induction agents (higher among patients induced with thiopentone 34 (24.3%) and lowest among propofol group 32 (22.9%) probably due to propofol effect of antioxidant like a-tocopherol and it accumulates in the biomembranes with an ability to form stable radicals and inhibits propagation of reactions involving free radicals to attenuate postoperative myalgia caused by succinylcholine [13, 35, 36]. This finding was in harmony with studiesconducted previously [5, 13, 37, 38].

Severity of fasciculation was identified and allocated as mild 41(29.3%), moderate 54(38.6%) and severe 37(26.4%) also differs among groups: mild fasciculation was more observed among ketamine group 15(10.7%) and lessseen among propofol group 7(5.0%). Moderate SIF was also dominantly observed among patients induced by propofol and ketamine (each 15(10.7%)). But, severe scale of SIF was higher among patients induced by thiopentone 13(9.3%) followed by ketofol 11(7.9%), propofol 10(7.1%) and ketamine 3(2.1%). This pattern was also supported by previous studies [39, 40]. Among total of 41 patients with mild fasciculation, majority was seen among patients induced by ketamine 15(10.7%) where the rest mild SIF was observed among thiopentone 11(7.9%), ketofol 8(5.7%) and propofol 7(5.0%).

The incidence of POM was 29.3% in general and varies among IV induction agents (highest ketamine 15(10.7%), followed by thiopentone and ketofol (each 10 (7.1%)) while minimal among propofol group 6(4.3%.This finding was also supported by other studies [13, 37-40].

In comparable with present finding, the study conducted by Mc- Clymont to compare POM among thiopentone and propofol reported that the propofol group had a significantly lower incidenceof suxamethonium myalgia (19%) compared with the thiopentone group (63%) (P<O.05) [41].

Even though, there is no statistically significant difference in the occurrence of POM, the present study revealed dominance of POM among ketamine group. But, Previous studies reported less incidence among ketamine due to ketamine effects of both antinociceptive and pronociceptive actions via NMDA receptor and aminergic (serotonergic and noradrenergic) receptors and possible interferes with nicotinic, muscarinic, monoaminergic and opioid receptors in abolishing pain [42]. The study conducted by Nasseri and Arvien that compared ketofol and propofolwas also reported high incidence of POM among propofol group than ketofol group against our finding [43]. Thus, further studies with large sample and strong design will be inspired to mediate the existing findings.

Conclusion

Even though, the incidence of both SIF and POM were profound and there is no statistically significant safe IV inductions that mitigate this adverse effect (fasciculation and POM) following administration of suxamethonium, other option of muscle relaxant was warranted/inspired at the setting and the country at all.

Acknowledgments

We would like to thank Jimma University for providing financial support and also extend our heartfelt gratitude to patients involved in the study.