Application of dezocine patient-controlled epidural analgesia in postoperative analgesia in patients with total myomectomy

Abstract

BACKGROUND

Uterine fibroids are common benign gynecological conditions. Patients who experience excessive menstruation, anemia, and pressure symptoms should be administered medication, and severe cases require a total hysterectomy. This procedure is invasive and causes severe postoperative pain, which can affect the patient’s postoperative sleep quality and, thus, the recovery process.

AIM

To evaluate use of dezocine in patient-controlled epidural analgesia (PCEA) for postoperative pain management in patients undergoing total myomectomy.

METHODS

We selected 100 patients undergoing total abdominal hysterectomy for uterine fibroids and randomized them into two groups: A control group receiving 0.2% ropivacaine plus 0.06 mg/mL of morphine and an observation group receiving 0.2% ropivacaine plus 0.3 mg/mL of diazoxide in their PCEA. Outcomes assessed included pain levels, sedation, recovery indices, PCEA usage, stress factors, and sleep quality.

RESULTS

The observation group showed lower visual analog scale scores, shorter postoperative recovery indices, fewer mean PCEA compressions, lower cortisol and blood glucose levels, and better polysomnographic parameters compared to the control group (P < 0.05). The cumulative incidence of adverse reactions was lower in the observation group than in the control group (P < 0.05).

CONCLUSION

Dezocine PCEA can effectively control the pain associated with total myomectomy, reduce the negative impact of stress factors, and have less impact on patients’ sleep, consequently resulting in fewer adverse effects.

Key Words: Diazoxide; Patient-controlled epidural analgesia; Total hysterectomy; Sleep impacts; Adverse effects

Core Tip: This study investigated the role of dezocine patient-controlled epidural analgesia (PCEA) in managing pain after total hysteromyectomy. Preliminary studies have found that dezocine PCEA can effectively control pain after the procedure, reduce the negative impact of stress factors, improve patients’ sleep quality, and result in fewer adverse reactions. The results of this study provide valuable insights for clinical anesthesia practices.

INTRODUCTION

Uterine fibroids are common benign gynecological conditions characterized by the abnormal growth of myometrial smooth muscle. They are most frequently diagnosed in women between 30 years and 50 years of age[1]. Asymptomatic cases usually do not require treatment. However, cases involving excessive menstruation, anemia, and pressure symptoms should be managed with medication, and severe cases require a total hysterectomy. This procedure is invasive and causes severe postoperative pain, which can affect the patient’s postoperative sleep quality and thus hinder the recovery process. Therefore, active postoperative analgesic treatment is required[2]. Patient-controlled epidural analgesia (PCEA) is a commonly used method for pain relief after total hysterectomy; however, there is no academic consensus on the optimal ratio of these drugs[3].

Dezocine is a κ-receptor agonist and μ-receptor antagonist with good analgesic effects and low potential for abuse. It is widely used in the treatment of postoperative, visceral, and cancer-related pain; however, its side effects include nausea, vomiting, dizziness, and respiratory depression, which can affect the sleep quality of patients[4]. In this study, we combined diazoxide with the local anesthetic drug ropivacaine for postoperative analgesia and observed the effect of the diazoxide PCEA modality on stress response and sleep quality in patients undergoing total hysterectomy.

MATERIALS AND METHODS

General information

In total, 100 patients who underwent total abdominal hysterectomy for uterine fibroids and who were admitted to our hospital between January 2020 and December 2021 were selected and divided into a control group (50 patients) and an observation group (50 patients) using a simple randomization method. General data such as age, weight, and surgical condition of the patients were collected and statistically analyzed. No statistical difference was found between the general conditions of the patients in the two groups (P > 0.05) (Table 1).

Table 1 Comparison of general data between the two groups.

Group	n	Age in yr	Height in cm	Weight in kg	Operation time in min	Anesthesia time in min	Intraoperative blood loss in mL	Intraoperative fluid volume in mL
Control group	50	45.56 ± 6.71	160.56 ± 5.26	58.23 ± 5.79	123.36 ± 14.85	125.87 ± 15.66	134.12 ± 15.22	1345.26 ± 74.25
Observation group	50	46.02 ± 6.34	161.04 ± 5.11	57.69 ± 6.21	121.26 ± 15.07	124.78 ± 14.98	130.25 ± 16.89	1331.56 ± 81.02
t		0.352	0.463	0.450	0.702	0.356	1.204	0.881
P value		0.725	1.984	0.654	1.984	0.723	0.232	0.380

Data are mean ± standard deviation.

Case selection

The inclusion criteria were as follows: (1) Patients diagnosed with uterine fibroids according to the guidelines in Chinese Obstetrics and Gynecology[5] and treated with TAH; (2) aged 18-55 years; (3) classified as grade I or II by the American Society of Anesthesiologists[6]; (4) no history of opioid abuse; (5) no comorbidities (e.g., hypertension or diabetes); and (6) voluntary participation with signed informed consent.

The exclusion criteria were as follows: (1) Use of analgesic drugs within 24 h before surgery; (2) a history of long-term use of sedative drugs; (3) allergy to any drugs used in the study; (4) preoperative sleep disorders, depression, or anxiety; and (5) presence of functional diseases of important organs.

Methods

All patients were connected to an intravenous self-controlled analgesic pump (Zhejiang Hai Sheng Medical Equipment Co., Ltd., model: CBI + PCA-100 mL) at the time of skin suturing. The normal flow rate was set at 2 mL/h, with an automatic control feed liquid flow rate of 0.5 mL/15 min. In the control group, 0.2% ropivacaine plus morphine 0.06 mg/mL was used for the analgesic pump formulation, while 0.2% ropivacaine plus 0.3 mg/mL of diazoxide was used in the observation group.

Observation indexes and detection methods

To compare the differences in pain, sedation scores, postoperative recovery index, number of PCEA presses, and stress factors between the two groups, the patients’ sleep quality was assessed using polysomnography (PSG), and adverse reactions were recorded.

Peripheral venous blood specimens were drawn from patients in both groups the day before surgery and at 6, 12, and 24 h after surgery. The specimens were divided into two parts: one part was used for blood glucose detection using a Hitachi 7600 automatic biochemical instrument, and the other part was processed by centrifugation at 3000 rpm for 10 min. The serum obtained was used for cortisol (Cor) detection by the electrochemiluminescence method, with the detection instrument being Roche E601 chemiluminescent immunoanalyzer.

PSG was performed 1 d before surgery, 1 d after surgery, and 2 d after surgery. Patients rested in the laboratory the night before the test to adapt to the environment, and formal recordings were initiated on the day of the test. The detection instrument used was a 1518 K PSG instrument from Japan Optoelectronics Company. Four leads were used: two for the ophthalmogram, placed 1 cm downward from the outer canthus of the eye, with the reference electrode placed on the earlobe; one for the tonic electromyogram, placed 1.5 cm next to the midline of the mandible; and one for the electroencephalogram. Polysomnographic parameters, such as total sleep time (TST), sleep efficiency (SE), rapid eye movement sleep percentage (REMS), and wakefulness index (AI), were recorded.

Scoring criteria

The degree of pain was assessed using the visual analog scale (VAS)[7], with a score range of 0-10; a higher score indicated more pain. The degree of sedation was assessed using the Ramsay score[8], with a score range of 1-6, which indicated the patient’s level of wakefulness to deep sleep; higher scores indicated a deeper level of sedation.

Statistical methods

Data were analyzed using SPSS 26.0 (IBM Corp., Armonk, NY, United States). Measures conforming to a normal distribution with homoscedasticity (e.g., number of PCEA presses, and stress factors) were described as mean ± SD, and a t-test was used for comparison. A χ² test was applied to compare count data (e.g., vomiting, skin itching). A P-value < 0.05 was considered statistically significant.

RESULTS

Comparison of VAS scores

The VAS scores at 4, 6, 12, 24, 36, and 48 h postoperatively were significantly lower in the observation group compared to the control group (P < 0.05) (Table 2).

Table 2 Comparison of visual simulation rating scores between the two groups.

Group	n	4 h after surgery	6 h after surgery	12 h after surgery	24 h after surgery	36 h after surgery	48 h after surgery
Control group	50	2.72 ± 0.56	3.21 ± 0.47	3.07 ± 0.41	3.19 ± 0.37	2.89 ± 0.41	2.54 ± 0.36
Observation group	50	2.16 ± 0.41	2.34 ± 0.38	2.22 ± 0.39	2.14 ± 0.34	2.06 ± 0.32	1.78 ± 0.31
t		5.705	10.178	10.622	14.776	11.284	11.312
P value		0.000	0.000	0.000	0.000	0.000	0.000

Data are mean ± standard deviation.

Comparison of sedation scores

The sedation scores at 4, 6, 12, 24, 36, and 48 h postoperatively in the observation group did not significantly differ from those in the control group (P > 0.05) (Table 3).

Table 3 Comparison of sedation scores between the two groups.

Group	n	4 h after surgery	6 h after surgery	12 h after surgery	24 h after surgery	36 h after surgery	48 h after surgery
Control group	50	2.73 ± 0.37	2.39 ± 0.41	2.01 ± 0.32	2.05 ± 0.36	1.97 ± 0.32	1.35 ± 0.26
Observation group	50	2.74 ± 0.35	2.32 ± 0.39	1.96 ± 0.29	2.02 ± 0.32	1.92 ± 0.25	1.33 ± 0.24
t		0.139	0.875	0.819	0.440	0.871	0.400
P value		0.900	0.384	0.415	0.661	0.386	0.690

Data are mean ± standard deviation.

Comparison of postoperative recovery indicators

The postoperative recovery indices of the observation group, such as the time to get out of bed, gastrointestinal function recovery-related indices, and hospitalization duration, were significantly shorter than those in the control group (P < 0.05) (Table 4).

Table 4 Comparison of postoperative recovery indexes between the two groups.

Group	n	Get out of bed time in h	Bowel sounds recovery time in h	Anal exhaust in h	Postoperative hospital stay in d
Control group	50	13.58 ± 3.14	16.98 ± 3.82	22.36 ± 2.13	3.89 ± 1.02
Observation group	50	10.41 ± 2.56	13.84 ± 2.59	18.74 ± 2.25	3.81 ± 1.14
t		5.533	4.811	8.262	0.370
P value		0.000	0.000	0.000	0.712

Data are mean ± standard deviation.

Comparison of stress-related indicators between the groups

There was no statistical difference between the two groups in terms of Cor and blood glucose levels on the day before surgery (P > 0.05). However, Cor and blood glucose levels were higher in both groups at 6, 12, and 24 h postoperatively compared to the levels on the day before surgery (P < 0.05). Furthermore, Cor and blood glucose levels in the observation group were significantly lower than those in the control group at 12 and 24 h postoperatively, with the differences being statistically significant (P < 0.05) (Table 5).

Table 5 Comparison of stress-related indicators between the two groups.

Group	n	Cor in nmol/L				Blood sugar in mmol/L
		1 d before surgery	6 h after surgery	12 h after surgery	24 h after surgery	1 d before surgery	6 h after surgery	12 h after surgery	24 h after surgery
Control group	50	285.63 ± 37.14	378.59 ± 48.77a	492.05 ± 74.63a	472.23 ± 67.85a	5.12 ± 0.36	6.15 ± 0.41a	7.14 ± 0.45a	6.97 ± 0.42a
Observation group	50	279.93 ± 41.78	368.74 ± 45.45a	441.74 ± 64.27a	389.62 ± 61.04a	5.15 ± 0.34	6.08 ± 0.39a	6.61 ± 0.42a	6.15 ± 0.35a
t		0.721	1.045	3.612	6.400	0.428	0.875	6.088	10.606
P value		0.473	0.299	0.000	0.000	0.669	0.384	0.000	0.000

^aP < 0.01 vs 1 d before surgery.

Data are mean ± standard deviation.

Comparison of polysomnographic parameters

On the day before surgery, there were no statistically significant differences between the polysomnographic parameters of the two groups (P > 0.05). However, at 1 and 2 d postoperatively, TST, SE, and REMS decreased in both groups compared to preoperative values, while the AI increased (P < 0.05). In the observation group, TST, SE, and REMS of PSG were lower than those of the control group at 1 and 2 d postoperatively, whereas the AI was higher, with the differences being statistically significant (P < 0.05) (Table 6).

Table 6 Comparison of polysomnography parameters between the two groups.

Group	n	1 d before surgery	1 d after surgery	2 d after surgery	1 d before surgery	1 d after surgery	2 d after surgery
		TST in min			SE, %
Control group	50	465.25 ± 47.85	358.12 ± 31.05a	382.02 ± 38.96a	96.58 ± 5.02	72.26 ± 4.22a	82.69 ± 4.91a
Observation group	50	471.56 ± 42.93	389.96 ± 35.22a	418.96 ± 42.56a	95.23 ± 5.27	79.56 ± 4.41a	87.16 ± 5.11a
t		0.694	4.795	4.527	1.312	4.981	4.460
P value		0.489	0.000	0.000	1.984	0.000	0.000
		REMS, %			AI, n/h
Control group	50	20.85 ± 3.12	14.02 ± 2.16a	15.89 ± 2.11a	1.54 ± 0.48	4.25 ± 0.63a	4.09 ± 0.45a
Observation group	50	20.79 ± 3.25	17.85 ± 2.48a	19.08 ± 2.37a	1.57 ± 0.45	3.17 ± 0.55a	2.61 ± 0.37a
t		0.094	8.235	7.109	0.322	9.132	17.963
P value		0.925	0.000	0.000	0.748	0.000	0.000

^aP < 0.01 vs 1 d before surgery.

Data are mean ± standard deviation.

Comparison of PCEA compressions

The mean number of PCEA compressions in the observation group was lower than that in the control group (P < 0.05). However, there was no statistically significant difference in the mean number of effective compressions between the two groups (P > 0.05) (Table 7).

Table 7 Comparison of patient-controlled epidural analgesia compressions between the two groups.

Group	n	Average number of compressions	Average number of effective compressions
Control group	50	2.02 ± 0.47	1.88 ± 0.44
Observation group	50	1.83 ± 0.41	1.75 ± 0.38
t		8.956	1.581
P value		0.000	0.117

Data are mean ± standard deviation.

Comparison of adverse reactions between the two groups

The most frequent adverse reaction in the control group was vomiting, with an incidence of 34.00% (17/50), followed by pruritus, with an incidence of 18.00% (9/50); the cumulative incidence of adverse reactions was 52.00% (26/50). Vomiting was the most frequent adverse reaction in the observation group as well, with an incidence of 14.00% (7/50). However, the cumulative incidence of adverse reactions in the observation group was lower than that in the control group (P < 0.05).

DISCUSSION

Uterine fibroids are common in women of reproductive age and often present without noticeable symptoms in the early stages. Some patients are diagnosed by physical examinations, suggesting that the reported clinical incidence of uterine fibroids may be lower than the actual incidence[9]. The etiology of uterine fibroids remains unclear; however, some studies have suggested that it is related to genetics and hormone levels. Total hysterectomy is generally recommended when the uterine fibroids are large and cause anemia due to massive hemorrhage[10]. This procedure is traumatic, causes severe postoperative pain, and significantly affects sleep, consequently affecting recovery. Therefore, postoperative analgesic treatment in this regard is receiving increasing clinical attention[11].

PCEA is a common method of self-controlled analgesia, typically using low concentrations of opioid analgesics. Morphine is currently the most commonly used analgesic drug for PCEA treatment owing to its effective pain relief. However, it can cause adverse reactions such as nausea and vomiting, particularly in patients who have undergone total hysterectomy[12], likely due to hormonal and endocrine factors. Dezocine is a phenylmorphanolane derivative whose analgesic effect is closely related to its dosage[13]. Studies comparing equivalent analgesic doses of sufentanil, fentanyl, and dezocine on consciousness levels and adverse reactions have found that dezocine has a better safety profile and less impact on consciousness[14].

The results of this study showed that the VAS scores at 4, 6, 12, 24, 36, and 48 h postoperatively in patients who underwent total hysterectomy with dezocine PCEA intervention were significantly lower than in those who underwent morphine PCEA intervention. There was no statistically significant difference between the sedation scores of the two groups. Patients receiving the dezocine PCEA intervention experienced faster recovery, including shorter times to ambulate, quicker gastrointestinal function recovery, and reduced hospital stays compared to those receiving morphine PCEA. Additionally, they required fewer PCEA compressions on average.

These results suggested that dezocine PCEA can more effectively control postoperative pain and accelerate postoperative recovery in total myomectomy. Ropivacaine, a long-acting amide local anesthetic drug, produces analgesia by blocking nerve roots in the epidural cavity, while dezocine can produce spinal analgesia not only by agonizing κ receptors but also by agonizing and antagonizing μ receptors. Evidently, these two drugs exert synergistic analgesic effects through different mechanisms, resulting in postoperative pain relief. Moreover, the analgesic effect of dezocine was slightly stronger than that of morphine alone.

Total hysterectomy is highly traumatic and inevitably induces a stress response. Strong stress responses can lead to decreased sleep quality and negative emotions by affecting the neuroendocrine system[15]. Cor is a stress hormone secreted by the body in large amounts under stressful conditions and can cause stress hyperglycemia[16]. In this study, perioperative Cor and blood glucose levels of patients were monitored and were found to be higher in both groups at 6, 12, and 24 h postoperatively compared to 1 d preoperatively. The levels at 12 and 24 h postoperatively were lower in the dezocine PCEA group than in the morphine PCEA group. This result suggests that the dezocine PCEA modality is effective in suppressing the stress response after total myomectomy. This effectiveness is related to its stronger analgesic effect, which suppresses sympathetic excitation and reduces the overproduction of pituitary and adrenal hormones induced by painful stimuli.

Severe pain can cause sleep disturbances, which may lead to hypersensitivity, cognitive decline, and dysfunction of the immune and endocrine systems, creating a vicious cycle that is detrimental to postoperative recovery and, in severe cases, can cause adverse cardiovascular events[17]. In this study, TST, SE, and REMS decreased and the AI increased in both groups 1 and 2 d postoperatively. TST, SE, and REMS on PSG were lower at 1 and 2 d postoperatively in the dezocine PCEA group compared to the morphine PCEA group, while the AI was higher. This suggests that sleep was less affected by the dezocine PCEA intervention due to its superior analgesic effect and suppression of the stress response. In addition, the cumulative rate of adverse reactions was lower in the dezocine PCEA group than in the morphine PCEA group, indicating that dezocine PCEA causes fewer adverse effects and has a superior safety profile.

CONCLUSION

In conclusion, dezocine PCEA can effectively control the pain associated with total myomectomy, reduce the stress response and impact on patients’ sleep, and cause fewer adverse effects.