Effect of Hyoscine-n-Butylbromide on Multimodal Analgesia for Laparoscopic Sleeve Gastrectomy: A Retrospective Case

Abstract

Background:

Nonsteroidal anti-inflammatory drugs are commonly used in addition to opioids after laparoscopic sleeve gastrectomy (LSG). The aim of this study was to demonstrate the analgesic effect of hyoscine-n-butylbromide, a spasmolytic agent, in addition to different analgesic protocols.

Methods:

Postoperative analgesia records of 134 patients who underwent LSG were analyzed. Patients were divided into four groups according to additional analgesics used. Paracetamol (Group 1, n = 33), dexketoprofen trometamol (Group 2, n = 34), paracetamol and hyocine-n-butylbromide (Group 3, n = 32), and dexketoprofen trometamol and hyocine-n-butylbromide (Group 4, n = 35). The method of analgesia, the visual analogue scale (VAS), the applied analgesic doses, and patient satisfaction scores and side effects were recorded.

Results:

The cumulative opioid consumption in Group 1 (352.03 ± 60.02 mg) was higher than that of Group 2 (291.73 ± 53.70 mg), Group 3 (186.81 ± 45.55 mg), and Group 4 (186.51 ± 46.78 mg) (p < 0.05). In addition, in Group 2 the consumption was higher than that of Groups 3 and 4 (p < 0.05). The patient satisfaction score was lower in Groups 1 and 2 than that of Groups 3 and 4, respectively (p < 0.001). VAS scores for Groups 1 and 2 were higher than that of Groups 3 and 4 (p < 0.001).

Conclusion:

Addition of hyoscine-n-butylbromide to analgesic protocols improves postoperative patient comfort, decreases VAS scores and opioid consumption in LSG.

Introduction

Postoperative pain is an acute pain that starts with surgical trauma. Relieving this acute pain is important for improving patient prognosis and preventing the development of chronic pain. Using a combination of different analgesics is an accepted method for improving analgesia and postoperative pain treatment, and minimizing the side effects of each drug.¹ Performing the sleeve gastrectomy operation with laparoscopic method decreases complication rates, shortens the duration of hospitalization, and provides a quicker return to normal life activities.² Postoperative pain control is important for decreasing the risk of pulmonary complications, which is higher because of the presence of morbid obesity.³ Opioids have strong analgesic effects and are frequently used in the treatment of postoperative pain. However, they have side effects such as sedation, dizziness, nausea and vomiting, and respiratory depression.⁴ Opioid usage, especially in morbidly obese patients, may adversely affect the respiratory system by causing postoperative atelectasis, disrupted gas exchange, or hypoxia.^5,6 Addition of local or regional anesthetic methods, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, and acetaminophen is recommended by The American Society of Anesthesiologists (ASA) to reduce the opioid consumption in patients who undergo bariatric surgery.⁷ A retrospective study evaluating the safety and efficacy of NSAIDs reported that the administration of NSAIDs reduced opioid consumption and the length of postanesthesia care.⁸

In this study, we retrospectively evaluated whether addition of hyoscine-n-butylbromide to analgesic agents in patients who underwent laparoscopic sleeve gastrectomy (LSG) decreased the side effects of opioids, or had any effects on postoperative pain control.

Methods

The study was approved by the local ethics committee. Postoperative analgesia records of the patients who underwent LSG between January 2015 and December 2018 were analyzed. Analgesia methods, doses, complications, and symptoms including postoperative nausea and vomiting were determined.

Postoperative analgesia management

Tramadol (intravenous [IV] patient-controlled analgesia) was routinely used as the only main analgesic in all patients, and patients were divided into four groups according to the additional analgesic in use.

Patient pain control was recorded from patient charts, and grouped as follows:

Group 1: One gram paracetamol (Perfalgan 10 mg/mL Falcon; Bristol-Myers Squibb Laboratories, Renaudin Itxassou, France) administered by IV infusion over a 15-min period at the end of the operation, and 1 g IV paracetamol administered every 6 h for 24 h after surgery.

Group 2: Fifty milligrams dexketoprofen trometamol (Arveles 50 mg/2 mL; Menarini International, Italy), diluted with 100 mL of saline, was administered over a 15-min period by IV infusion at the end of the surgery, and the same dose repeated every 8 h on the first postoperative day.

Group 3: One gram paracetamol was administered by IV infusion over a 15-min period at the end of the operation, followed by administration of 20 mg IV hyoscine-n-butylbromide (Buscopan, 20 mg/mL; Eczacıbaşı, Turkey) during skin closure. In addition, 1 g IV paracetamol was administered every 6 h for 24 h after surgery, as in Group 1.

Group 4: Fifty milligrams dexketoprofen trometamol, diluted with 100 mL of saline, was administered over a 15-min period by IV infusion at the end of the surgery, and followed by addition of 20 mg IV hyoscine-n-butylbromide during skin closure. Diluted dexketoprofen trometamol (50 mg) dose was repeated every 8 h on the first postoperative day, as in Group 2.

Statistical analysis

The data were analyzed using IBM SPSS 22.0 statistical software package. Normality assessment was made with Kolmogorov–Smirnov test. Descriptive data were evaluated as the means, standard deviations, and percentages. Independent two-sample t-test and one-way analysis of variance (ANOVA) were used for continuous variables in ASA scores and group comparisons. The Scheffe test was used for post hoc analysis of ANOVA. Pearson's χ² test was used to determine the differences between the groups in categorical variables. p < 0.05 was considered statistically significant.

Results

There were 134 patients with full charts, including preoperative and postoperative data, who underwent LSG between January 2015 and December 2018. It was observed that 57.5% of the patients were women, 39.6% were in the 26–35 age group, average analgesia duration was 80.83 ± 7.6 min, and 43.3% of the patients reported good satisfaction. There was no significant correlation between ASA, age, sex, duration of anesthesia, duration of surgery, and the amount of opioid needed (p > 0.05). The demographics of the patients are given in Table 1.

Table 1.

Opioid Use According to Defining Features

	n	%	Opioid use (mg), mean ± SD	Test	p
Analgesic protocol^*				F, 83.070	<0.001
Group 1^b	33	24.6	352.03 ± 60.02
Group 2^c	34	25.4	291.73 ± 53.70
Group 3^a	32	23.9	186.81 ± 45.55
Group 4^a	35	26.1	186.51 ± 46.78
ASA				t, 1.168	0.246
ASA II	68	50.7	262.73 ± 77.95
ASA III	66	49.3	245.09 ± 96.15
Sex				t, −1.712	0.089
Female	77	57.5	242.98 ± 84.03
Male	57	42.5	268.98 ± 90.60
Age	X = 30.8 ± 7.89
18–25	40	29.9	256.40 ± 78.74	F, 1.507	0.225
26–35	53	39.6	266.67 ± 85.02
36+	41	30.6	235.41 ± 97.19
Duration of anesthesia (min)	X = 80.83 ± 7.6
68–78	51	38.1	258.92 ± 91.98	F, 0.532	0.589
79–88	61	45.5	245.83 ± 85.51
89–90	22	16.4	265.50 ± 84.09
Duration of surgery (min)	X = 77.09 ± 7.8
65–75	70	52.2	249.74 ± 85.18	F, 0.179	0.836
76–85	43	32.1	258.06 ± 90.32
86–95	21	15.7	260.14 ± 92.85
Patient satisfaction^*
Bad^b	30	22.4	316.50 ± 69.20	F, 27.988	<0.001
Mild^b	46	34.3	279.26 ± 82.61
Good^a	58	43.3	201.74 ± 68.52
BMI	X = 34.00 ± 2.25

Significance results from differences between groups referred with different letters.

ASA, American Society of Anesthesiologists; BMI, body mass index; F, one-way analysis of variance; SD, standard deviation; t, t-test in independent groups; X, mean.

There was a significant difference between the groups in terms of the total amount of opioid consumed (p < 0.001). Post hoc analysis revealed that cumulative opioid consumption of Group 1 was significantly higher than that of Groups 2, 3, and 4. In addition, cumulative opioid consumption of Group 2 was significantly higher than that of Groups 3 and 4 (p < 0.001). Cumulative opioid consumption was not significantly different between Groups 3 and 4 (p > 0.05; Table 1).

A significant difference was found between the groups in terms of patient satisfaction. The satisfaction indexes of the patients in Groups 1 and 2 were significantly lower than the satisfaction indexes of the patients in Groups 3 and 4 (p < 0.001; Table 2). It was also determined that cumulative opioid consumption of the groups with high satisfaction index (Groups 3 and 4) was significantly lower than the other groups (p < 0.001; Table 1).

Table 2.

Patient Satisfaction States According to Analgesia Group

Features	Bad, n (%)	Mild, n (%)	Good, n (%)	Total, n (%)	Test
Features	Bad, n (%)	Mild, n (%)	Good, n (%)	Total, n (%)	χ²	p
Group 1	16 (53.3)	12 (26.1)	5 (8.6)	33 (24.6)	51.07	<0.001
Group 2	13 (43.3)	15 (32.6)	6 (10.3)	34 (25.4)
Group 3	1 (3.4)	9 (19.6)	22 (37.9)	32 (23.9)
Group 4	0 (0)	10 (21.7)	25 (43.1)	35 (26.1)
Total	30 (22.4)	46 (34.3)	58 (43.3)	134 (100.0)

χ² = Pearson chi-square analysis.

The mean visual analogue scale (VAS) score of the patients varied between 3.90 ± 0.67 and 2.34 ± 0.83 in all groups. When the difference between the VAS scores of the patients were evaluated at 1, 2, 4, 8, 12, and 24 h, according to the analgesic type, a significant difference between the groups was found. The VAS scores of the patients in Groups 1 and 2 were significantly higher than those of Groups 3 and 4 (p < 0.001; Table 3).

Table 3.

Relation Between Patient Analgesia Group and Visual Analogue Scale

	VAS 1st hour	VAS 2nd hour	VAS 4th hour	VAS 8th hour	VAS 12th hour	VAS 24th hour
Analgesia protocols^* (mean ± SD)
Group 1^a	3.90 ± 0.67	3.75 ± 0.66	3.75 ± 0.66	3.39 ± 0.70	3.72 ± 0.62	3.48 ± 0.71
Group 2^a	3.85 ± 0.70	3.58 ± 0.49	3.58 ± 0.49	3.15 ± 0.85	3.23 ± 0.74	2.50 ± 1.02
Group 3^b	2.90 ± 0.58	2.68 ± 0.53	2.68 ± 0.53	2.46 ± 0.76	2.62 ± 0.60	1.93 ± 0.66
Group 4^b	2.94 ± 0.59	2.71 ± 0.82	2.71 ± 0.82	2.40 ± 0.84	2.34 ± 0.83	2.05 ± 0.80
Average	3.40 ± 0.79	3.18 ± 0.80	3.18 ± 0.80	2.85 ± 0.89	2.97 ± 0.88	2.49 ± 1.00
Test
F	24.775	25.548	25.548	12.868	25.511	24.541
P	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

Groups referred with different letters are different from one another.

VAS, visual analogue scale.

No significant difference was found between the groups in terms of side effects. One patient in Groups 1, 3 and 4, and two patients in Group 2 had nausea. No patients had sedation, dizziness, somnolence, or respiratory depression.

Discussion

In this study, it was observed that after LSG, addition of hyoscine-n-butylbromide alongside opioids in pain control decreased the total opioid consumption on the first day postoperatively, and increased the satisfaction of the patient. This positive effect of hyoscine-n-butylbromide addition is more prominent when added to dexketoprofen trometamol than to paracetamol.

After LSG, opioids are widely preferred because of their strong analgesic activity.⁹ Tramadol is an opioid known to be effective and safe in multimodal analgesia after bariatric surgery.¹⁰ Therefore, tramadol is the preferred analgesic for patient-controlled analgesia after LSG in our clinic. However, to avoid complications associated with high-dose opioid use, such as airway obstruction, postoperative ileus, prolonged hospital stay, nausea, and vomiting,^6,11,12 the total amount of opioid used should be reduced by adding nonopioid analgesics. This is especially important in morbidly obese patients with obstructive sleep apnea syndrome.

There are many articles demonstrating the effectiveness of paracetamol addition to opioids after LSG.^13,14 IV paracetamol is a suitable drug in the treatment of mild and moderate postoperative pain without the adverse effects of NSAIDs. Gonzalez et al.¹⁴ reported that the use of IV acetaminophen in the perioperative period reduced the need for opioids in patients undergoing LSG. A study comparing the efficacy of IV paracetamol and IV ibuprofen in pain treatment in LSG reported that ibuprofen was more effective, especially in the first 2 h, and it could be used as an alternative drug in multimodal analgesia.⁹ In the same study, side effects such as nausea and itching were observed to be lower in the ibuprofen group than the control and paracetamol groups.

Dexketoprofen trometamol is an active enantiomer of racemic ketoprofen. To our knowledge, there is no study using dexketoprofen in pain treatment after LSG. However, Kılıçkaya et al.¹⁵ stated that addition of IV dexketoprofen trometamol to tramadol after major abdominal surgery reduced the consumption of cumulative tramadol. Akıncı et al.¹⁶ stated that usage of parenteral dexketoprofen 30 min before the procedure in endoscopic retrograde cholangiopancreatography reduced the need for additional doses of fentanyl, more than paracetamol and placebo. This study also emphasized the superiority of dexketoprofen to paracetamol.

Hyoscine-n-butylbromide, which is a quaternary ammonium compound with anticholinergic properties, acts through nicotinic and muscarinic receptors.¹⁷ It is barely absorbed from the gastrointestinal tract and does not cross the blood–brain barrier. It is presumed to act locally from the luminal side of the gut wall.^18,19 It relaxes smooth muscles of the gastrointestinal tract, and bile and excretory systems. Thus, it acts by correcting the formed spasms. For >60 years, hyoscine-n-butylbromide has found widespread use as a spasmolytic and smooth muscle relaxant in the treatment of abdominal pain.²⁰

In our clinic, in addition to opioids, paracetamol, and dexketoprofen trometamol were preferred analgesics. It is known that NSAIDs are rarely effective in improving abdominal pain with cramping, as they do not address the underlying cause—abdominal spasms and cramps—when used alone.¹⁴ Consistent with the results of this study, our clinical observation was also that the need for opioids was higher when only paracetamol was added. Thus, we decided to add hyoscine-n-butylbromide along with paracetamol or dexketoprofen trometamol during the skin closure, to increase the analgesic effectiveness by its spasmolytic effect. In accordance with our previous unreported clinical observations, our study demonstrated that opioid consumption was significantly lower in both hyoscine-n-butylbromide groups (Groups 3 and 4) than the groups in which only paracetamol or dexketoprofen were used.

Patient satisfaction is important when evaluating postoperative analgesic level. A study evaluating the effects of a single preoperative dose of pregabalin reported no difference between placebo and treatment groups in terms of patient satisfaction, but two patients in the placebo group perceived the treatment as “bad.”²¹ According to our opinion, in our study, the reason for significantly higher patient satisfaction in the hyoscine-n-butylbromide treatment groups was because of the elimination of spasm-induced discomfort in the early postoperative period.

Our study has several limitations, caused mostly by the retrospective design. Only the pain control data of the patients were evaluated and the good or bad effects in terms of surgical complications in the long term were not evaluated. Another significant limitation of our study was that we could not reach the data about the pain type of the patients. Similarly, the recovery times of gastrointestinal system functions, and the relation to postoperative analgesia, could not be evaluated.

Conclusions

Motility is regulated and spasm formation is prevented with the application of hyoscine-n-butylbromide in LSG, in which a large part of the stomach is removed. Addition of hyoscine-n-butylbromide reduces the need for additional analgesics. Thus, a multimodal analgesia approach is advisable in this patient group. This study demonstrated that addition of hyoscine-n-butylbromide to analgesics would increase patient comfort and decrease opioid consumption. Further prospective randomized studies with a larger sample size should be planned to evaluate the side effects and long-term surgical complications.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this research.

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Effect of Hyoscine-n-Butylbromide on Multimodal Analgesia for Laparoscopic Sleeve Gastrectomy: A Retrospective Case–Control Study