Prevalence and associated factors of postoperative suxamethonium-induced myalgia in surgical patients at Debre Tabor Comprehensive Specialized Hospital Ethiopia: a cross-sectional study

Abstract

Suxamethonium is considered by many to be the best drug for providing ideal intubating conditions, short surgical procedures, and rapid sequence induction. However, its usefulness is limited by the frequent occurrence of adverse effects like postoperative myalgia. Therefore this study aimed to assess the prevalence and associated factors of postoperative suxamethonium-induced myalgia. An institutional-based cross-sectional study was conducted on 210 patients who underwent surgery with general anesthesia. The data was collected by using structured and pretested questionnaires and analyzed using SPSS version 20.0. Logistic regression was conducted to identify significant predictors based on a P-value of less than 0.05 with a 95% confidence level. Among 210 patients the prevalence of suxamethonium-induced postoperative myalgia in the first 48 h was 88 (41.9%). Patients having previous anesthesia and surgical exposure (AOR 5.29, 95% CI 1.86–15.05), patients having a co-existing disease (AOR 2.69, 95% CI 1.08–6.67), patients that had not taken premedication (analgesia) (AOR 4.64, 95% CI 1.69–12.74), anesthesia maintenance using halothane (AOR 4.5 95% CI 1.7–11.4) and relaxation maintained with suxamethonium (AOR 3.1, 95% CI 1.2–8.1) were significantly associated with the prevalence of postoperative myalgia. The magnitude of suxamethonium-induced postoperative myalgia was high. So it is better to do with preventive techniques. As much as possible it is better to avoid using suxamethonium and necessary to use better to Premedicate with nonsteroidal anti-inflammatory drugs and non-depolarizing neuromuscular medications.

Introduction

Improving patient safety during anesthesia and surgery is a major global public health issue due to an increased surgical burden¹. Improving the quality of surgical and anesthesia care service delivery with the implementation of a national perioperative guideline and WHO Surgical Safety Checklist is one of the initiatives activity².

Although there are different challenges and problems, every surgical operation is done under the provision of anesthesia³. Suxamethonium is the most available short-acting neuromuscular blocker used to facilitate tracheal intubation as part of general anesthesia^4–8. But, it causes adverse events such as malignant hyperthermia, rhabdomyolysis, hyperkalemia, muscle pain (myalgia), and so on^5,9.

Suxamethonium-induced myalgia is frequently described as a mild side effect. But, the patient may find it to be extremely upsetting^5,8,10–12. Vigorous muscle contraction/fasciculation following suxamethonium administration resulted in fiber damage or rupture, which would hurt the muscle by the shearing forces of fasciculation at the beginning of the phase one block^6,13. Lastly, it ends with a sensation of muscular rigidity and myalgia postoperatively^14,15.

According to different studies, the prevalence of suxamethonium-induced myalgia varies from 18.1 to 89%, with around 50% being the most frequently reported^6,10,16–18. The onset and duration of the discomfort is variable across different patients. Although it mainly manifests on the first day of surgery, it often lasts two to three days, but it can last up to a week. It mostly occurs following intense physical activity and typically affects the neck, shoulder, and upper abdominal muscles^5,6,8.

Different factors including patient characteristics [age, gender, and body mass index (BMI)]^19–22, surgical factors (duration of surgery, type of surgery) and anesthesia-related factors (dose and timing of suxamethonium administration, types of induction^23–25, use of non-depolarizing muscle relaxants, preoperative administration of magnesium, lidocaine, and steroids can determine the prevalence of myalgia^26–28. Although this can be a source of distress to patients and affects patients’ quality of life, it is not well investigated in the study area. Therefore, this study aimed to evaluate the prevalence and contributing factors of postoperative myalgia following suxamethonium in all patients who underwent surgery under general anesthesia.

Methods

Study design, area, and period

An institutional-based prospective cross-sectional study was conducted at Debre Tabor Comprehensive Specialized Hospital from June 01 to September 30, 2022.

Population

All patients who underwent surgery under general anesthesia during the study period were the study population.

Eligibility criteria

All patients with the age range of 18–65 and a BMI of < 35 were included. But, patients who have undergone surgery under general Anesthesia (GA) without relaxation, with GA after failed regional anesthesia, who were admitted to the Intensive care Unit (ICU), with a neuromuscular disorder, and administration of non-depolarizing muscle relaxant (NDMR) before suxamethonium were excluded.

Sampling size and sampling technique

The sample size was determined by using a single population proportion formula by considering 95% CI, a 5% margin of error, and the prevalence of myalgia. Since there was no previous study in the study area with a similar topic, a 50% prevalence of myalgia was assumed to get the maximum sample size.

$$n=\frac{{\text{z}}^2\left(\text{p}\right)\left(1-\text{p}\right)}{d^2}$$

where; n—sample size, p—proportion (50%)., d—Precision (0.05)

$$\text{n}=\frac{{(1.96)}^{2}0.5\left(1-0.5\right)}{0.05^2}\approx 384$$

According to previous operations logbook recordings, 463 patients underwent surgery under GA in the study area within four months. Since the patient flow is uniform throughout the year, we consider this number as the total population for our four-month study period, and the final sample size was calculated by applying a finite correction formula.

$$Nf=n/\left(1+n/N\right)$$

where Nf = the minimum sample size; n = sample size (384) & N = Total number of operations under general anesthesia within the study period (463).

$$\text{Nf}=384/\left(1+384/463\right)\approx 210$$

Therefore, those 210 patients were included in the study by non-probability convenience sampling technique.

Study variable

Independent variable

Sociodemographic characteristics (Age, Sex, Ethnicity, Occupation, religion), Physical and medical condition, American Society of Anesthesiologists (ASA) physical status, medication exposure history, induction agent, the dose of muscle relaxant (MR), duration of anesthesia and surgery.

Dependent variable

The primary outcome of this study was the prevalence of postoperative myalgia.

Data collection technique and procedure

Data were collected through an interview by using a data collection tool that was prepared based on previous studies done on a similar topic²⁹. Data were collected by an assigned anesthetist and an anesthesia student assigned at the workplace, supervised by one senior anesthetist. The data was collected between the 24th and 48th hours postoperatively (Supplementary information).

Data quality assurance

A pre-test was done to check the data collection tool and ambiguities and incompleteness were corrected before the actual data collection. Also, training was given to the data collectors, and data was collected and properly filled in the prepared format. Then the questionnaire was checked for its accuracy, clarity, and consistency. Incomplete data were rejected immediately and other study participants were considered to reach the sample size by the study supervisor.

Statistical analysis

For statistical analysis, the data were coded and entered into SPSS version 20. Clinical and sociodemographic categorical data were reported using frequencies and percentages of occurrence with a 95% confidence interval. Bivariate and multivariate logistic regression were used to investigate the relationship between independent variables and the dependent variable. A multivariate logistic model was fitted to variables from the bivariate analysis with a p-value of less than 0.2. A significant link between the outcome factors and the adjusted odds ratio was defined as one with a 95% confidence interval and a p-value of less than 0.05.

Ethics approval and consent to participate

This study was conducted per the declaration of Helsinki for human data. Ethical clearance and permission to conduct the research were obtained from the ethics committee of the College of Health Science, Debre Tabor University with the approval number of CHS/198/2022. Also, written and verbal informed consent was presented and obtained from each study participant.

Result

Sociodemographic characteristics of the patient

A total of 210 patients with a response rate of 100% and a mean age of 44.4 ± 17.5 were participated in this study. The majority of the participants 145 (69%) had a normal BMI (18.5–24.9 kg/m²). Of the participants, 119 (56.7%) were female and 142 (67.6%) came from rural areas (Table 1).

Table 1.

Sociodemographic characteristics of study participants at Debre Tabor Comprehensive Specialized Hospital from June 01 to September 30, 2022 (N = 210).

Variables	Category	Outcome variable (myalgia)
		No [count (%)]	Yes [count (%)]
Age (year)	18–45	70 (59.3)	48 (40.7)
	≥ 45	52 (56.5)	40 (43.5)
BMI (kg/m2)	< 18	16 (13.1)	12
	18.5–24.9	87 (60)	58 (40)
	25–29.9	6 (37.5)	10 (62.5)
	30–35	13 (61.9)	8 (38.1)
Sex	Male	51 (56)	40 (44)
	Female	71 (59.7)	48 (40.3)
Religion	Christian	107 (61.1)	68 (38.9)
	Muslim	15 (42.9)	20 (57.1)
Residence	Urban	36 (52.9)	32 (47.1)
	Rural	86 (60.6)	56 (39.4)
Educational status	Literate	51 (56)	40 (44)
	Illiterate	71 (59.7)	48 (40.3)
ASA status	ASA 1	69 (55.2)	56 (44.8)
	ASA 2	53 (62.4)	32 (37.6)
Presence of coexisting disease	Yes	44 (47.8)	48 (52.2)
	No	78 (66.1)	40 (33.9)
Previous anesthesia & surgery exposure	Yes	26 (39.4)	40 (60.6)
	No	96 (66.7)	48 (33.3)

ASA American Society of Anesthesiologist, BMI Body mass index.

Anesthesia and surgery-related characteristics of study participant

The majority of patients 127(60.5%) underwent elective surgery. Among the participants 103(49.05%) were general surgery, 52(24.8%) were gynecological /obstetrical (Gyn/obs) and 33(15.7%) were orthopedic procedures (Table 2).

Table 2.

Anesthetic and surgery-related characteristics of study participants at Debre Tabor Comprehensive Specialized Hospital from June 01 to September 30, 2022 (N = 210).

Variables	Category	Outcome variable (myalgia)
		No	Yes
Type of surgery	Elective	69 (54.3)	58 (45.7)
	Emergency	53 (63.9)	30 (36.1)
Premedication	Yes	63 (48.1)	68 (51.9)
	No	59 (74.7)	20 (25.3)
Specialty	General surgery	61 (59.2)	42 (40.8)
	Gyn/obs	36 (69.2)	16 (30.8)
	Orthopedic	17 (51.5)	16 (48.5)
	Others	8 (36.4)	14 (63.6)
Induction agent	Ketamine	61 (65.6)	32 (34.4)
	Thiopental	21 (44.7)	26 (55.3)
	Propofol	40 (57.1)	30 (42.9)
Dose of suxamethonium	Repeated dose	35 (59.3)	24 (40.7)
	Single dose	87 (57.6)	64 (42.4)
Anesthesia maintenance	Isoflurane	36 (69.2)	16 (30.8)
	Halothane	86 (54.4)	72 (45.6)
Maintenance of muscle relaxant	Vecuronium	104 (61.9)	64 (38.1)
	Suxamethonium	18 (42.9)	24 (57.1)

Gyn/obs Gynecologic/obstetrical operations.

The incidence of myalgia and related data

Among 210 surgical patients, 88 [41.9% (95% CI 35.2–49%)] were developed postoperative suxamethonium-induced myalgia. Of these, 35 (39.8%) patients had a limitation on the activity of daily living. Forty-four (50%) patients took analgesic agents to relieve the muscle pain. The majority of muscle pain complained from the abdomen, and 36.4% of myalgia was detected within the first 6 h (Fig. 1).

Figure 1.

Characteristics related to postoperative suxamethonium-induced myalgia.

Factors associated with post-operative suxamethonium-induced myalgia

After binary logistic regression, seven factors were fitted for multivariate logistic regression. From those seven factors, the presence of coexisting disease, previous exposure to anesthesia and surgery, lack of premedication, use of halothane for anesthesia maintenance, and maintenance of relaxant with suxamethonium were found to have a statistically significant association with the outcome variable (Table 3).

Table 3.

Factors associated with suxamethonium-induced myalgia in patients who underwent surgery under general anesthesia (N = 210).

Variable	COR (95% CI)	AOR (95% CI)	P value
Having coexisting disease
Yes	2.13 (1.22–3.72)	4.6 (2.2–9.9)	0.0001*
No	1	1
Previous anesthesia and surgery exposure
Yes	3.1 (1.68–5.62)	7.8 (3.4–17.6)	0.0001*
No	1	1
Premedication taken
No	3.18 (1.73–5.87)	7.2 (3.2–16.2)	0.0001*
Yes	1	1
Types of surgery
Elective	1.49 (0.84–2.62)	0.8 (0.4–1.7)	0.54
Emergency	1	1
Induction agent
Thiopental	2.36 (1.15–4.83)	2.4 (0.9–5.9)	0.058
Ketamine	1	1
Anesthesia maintenance
Halothane	1.88 (0.97–3.67)	4.5 (1.7–11.4)	0.002*
Isoflurane	1	1
Maintenance of relaxation
Suxamethonium	2.17 (1.1–4.3)	3.1 (1.2–8.1)	0.02*
Vecuronium	1	1

*Significantly associated factors, AOR Adjusted odds ratio, COR crud odds ratio.

Discussion

Suxamethonium is a commonly used neuromuscular relaxant for intubation and short procedures. It causes vigorous contraction of muscle bundles with no possibility of shortening and without synchronous activity in adjacent bundles which is called fasciculation. This might produce fiber rupture or damage, thus causing pain which is myalgia^28,30,31.

The postulated mechanisms for postoperative myalgia include increased intracellular calcium concentrations, membrane phospholipid degradation, and release of free fatty acids and free radicals, which lead to increased membrane permeability. It has been proposed that the pain occurs due to muscle damage produced by shearing forces associated with the fasciculation at the onset of phase one block³².

The magnitude of postoperative myalgia in this study was 41.9% (95% CI 35.2–49%) which is in agreement with studies done in Ethiopia, Wolaita (46%)³³, and Ankara, Turkey (41.5%)³⁴. But it is higher than studies done in Ethiopia, Jimma (29.5%)²³, Delhi, India (30%)³⁵, at Hacettepe University, Ankara, Turkey 33.33%, and in Liverpool, England (15.7%)¹⁹. It is also lower than the findings of systematic review done in Iran (50%)^8,28, in India (41–92%)^18,36–40, and Queens's University of Belfast (35–60%)⁴¹. The possible explanation and justification for this discrepancy might be due to variations in sociodemographic characteristics. Sociodemographic factors like age, gender, BMI, income, educational status, and living conditions are known to have different incidences in magnification of pain^20,22.

In this study, the incidence of suxamethonium-induced myalgia at 6 h, 12 h, 24 h, and 48 h was 36.4%, 19.3%, 21.6%, and 22.7% respectively. According to a study done in Ethiopia, the incidence of myalgia at 12 h and 24 h was 46% and 34% respectively¹⁶. Also, this study revealed that the prevalence of postoperative myalgia at the neck, shoulder, arm, and abdominal area was 21.6%, 13.6%, 29.5%, and 35.5% respectively.

In multivariable logistic regression, suxamethonium-induced myalgia is significantly associated with the presence of coexisting diseases, previous exposure to anesthesia and surgery, not premedicated, anesthesia maintained with halothane, and relaxation maintenance of suxamethonium were significantly associated with suxamethonium induced postoperative myalgia.

In this study patients with coexisting conditions are five times more likely to have postoperative suxamethonium-induced myalgia (AOR 4.6, 95% CI 2.2–9.9). Patients with coexisting disease will be at risk of muscular degradation and damage and are associated with an increased prevalence of myalgia. The possible justification for this factor might be that, pain is associated with psychological factors like pain catastrophizing conditions, depression, and anxiety by decreasing the pain threshold^21,42,43. Therefore patients with previous exposure to anesthesia are suspected to have a high level of pain-catastrophizing conditions like anxiety and depression. The other possible justification might be general anesthesia can activate the peripheral nociceptive ion channel to enhance pain with an unexplored mechanism of action⁴⁴.

In the current study, patients having previous anesthesia and surgical exposure were around eight times more likely to have postoperative suxamethonium-induced myalgia (AOR 7.8 95% CI 3.4–17.6). It is supported by a study that revealed that patients who had undergone repeated surgeries or with a history of anesthesia exposure were more likely to experience myalgia after surgery. This might be due to anesthesia can cause muscle relaxation, leading to increased muscle tension and subsequent pain. Furthermore, repeated exposure to anesthesia can result in the accumulation of anesthetic agents in the body, causing prolonged muscle relaxation and increasing the risk of myalgia⁴⁴. Also repeated surgery might cause muscles to stretch, compress, or cut, which can lead to tissue damage and inflammation, and as a result postoperative muscle pain occurs.

Patients who hadn’t taken premeditations like non-steroidal anti-inflammatory drugs (NSAIDs) were around seven times more likely to develop suxamethonium-induced postoperative myalgia (AOR 7.2; 95% CI 3.2–16.2). This is supported by studies that revealed, that patients premedicated with diclofenac had a significant reduction in the prevalence and intensity of myalgia^{16,32,36,39,40}. Also, it is supported by another study that showed that pretreatment with oral aspirin and Ketorolac was effective in the reduction of suxamethonium-induced myalgia prevalence^40,45. An RCT done at the Medical School, University of the Saarland, Homburg, Germany revealed that pretreatment with diclofenac was the best preventive strategy for suxamethonium-induced myalgia²⁸.

Patients who were maintained for relaxation with suxamethonium were around three times riskier than vecuronium maintenance to develop postoperative myalgia (AOR 3.1, 95% CI 1.2–8.1). This might be due to an increased dose of suxamethonium during the maintenance of relaxation with suxamethonium. It is supported by the systematic review that showed an increased dose of suxamethonium associated with an increased prevalence of myalgia^46,47. Also, increased exposure to suxamethonium during prolonged surgery increases the prevalence of myalgia⁴⁸. Generally, serum inflammatory cytokines and muscle damage markers are positively correlated with acute postoperative pain following surgery⁴⁹. When skeletal muscles are stimulated repetitively their mechanical output decreases progressively with time which leads to muscle fatigue⁵⁰.

Anesthesia maintenance with halothane is more risky for the development of postoperative muscle pain (AOR 4.5 95% CI 1.7–11.4). In fact, according to preexisting evidence, the prevalence of myalgia was significantly higher in patients who received halothane for anesthesia compared to those who received other anesthetic agents such as propofol or isoflurane^51,52. The possible explanation for this effect might be the mechanism of its action. Halothane is known to act on the neuromuscular junction leading to a decrease in muscle tone and relation. The exaggerated relaxation of muscles due to the synergetic effects of both halothane and suxamethonium may lead to strain and micro-trauma, resulting in myalgia postoperatively. Another possible justification for this effect might be due to the metabolism of halothane by which the metabolites of halothane called trifluoroacetate protein is postulated to cause muscle damage and result in postoperative myalgia.

Conclusion

In this study, the prevalence of suxamethonium-induced myalgia was high [41.9% (95% CI 35.2–49%)]. The presence of preexisting medical conditions, not premedicated with analgesics like NSAIDs, relaxation maintained with suxamethonium, and anesthesia maintenance with halothane were significantly associated with postoperative suxamethonium-induced myalgia. Therefore it is better to premeditate patients with NSAIDs if it is necessary to use suxamethonium relaxant. If possible it is better to avoid using suxamethonium relaxant.

Limitation

The limitation of this study was a small sample size and a single center. Also, it didn’t answer the dose-dependent effects of suxamethonium.

Author contributions

All authors contributed equally contribute to the preparation, reviewing, and correction of the manuscript.

Data availability

All the necessary data will be found from the corresponding author for a reasonable request.

Competing interests

The authors declare no competing interests.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-024-65779-7.