Effect of intraoperative mild hyperventilation on the incidence of shoulder pain after laparoscopic sleeve gastrectomy: A randomized, controlled trial

Backgrounds:

To observe the effect of using mild intraoperative hyperventilation on the incidence of postlaparoscopic shoulder pain (PLSP) in patients undergoing laparoscopic sleeve gastrectomy.

Methods:

Eighty patients undergoing laparoscopic sleeve gastrectomy, aged 22 to 36 years, with American Society of Anesthesiologists grade I or II, were divided into 2 groups according to method of random number table. A mild hyperventilation was used in group A with controlling pressure of end-tidal carbon dioxide (P_ETCO₂) of 30 to 33 mm Hg, while conventional ventilation was used in group B with P_ETCO₂ 35 to 40 mm Hg during the operation. The incidence and severity of PLSP, dosage of remedial analgesia and adverse reactions such as nausea and vomiting at 12, 24, 48, 72 hours and 1 week after surgery were recorded. Arterial blood gas was recorded before anesthesia induction, 20 minutes after pneumoperitoneum, during suture skin, and 24 hours after surgery.

Results:

Compared with 12, 24, 48, and 72 hours after operation, the incidence of PLSP at 1 week decreased significantly (P < .01). Compared with group B, the incidence of PLSP, pain score, and dosage of remedial analgesic at 12, 24,48, 72 hours, and 1 week after surgery were significantly decreased (P < .01). There was no significant difference between the 2 groups in arterial blood gas analysis before anesthesia induction, 20 minutes after pneumoperitoneum, during suture skin, and 24 hours after surgery (P > .05). There were no significant difference of the occurrence of adverse reactions such as nausea and vomiting between the 2 groups within 1 week after surgery (P > .05).

Conclusion:

Mild hyperventilation can reduce the incidence and severity of PLSP after laparoscopic sleeve gastrectomy without increasing the associated adverse effects.

1. Introduction

Obesity is a global health problem with the improvement of living standards. With a series of health problems and related comorbidities caused by obesity, which seriously affect people’s quality of life, the treatment of obesity has also received more and more attention.^[1,2] Bariatric surgery was a safe and effective long-term treatment for obesity, with long-term loss of weight, alleviate obesity-related comorbidities, improve quality of life, and prolong survival.^[3] Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Rouxen-Y gastric bypass (LRYGB) were the 2 most common weight loss procedures.^[4] In 2013, LSG surgery surpassed LRYGB to become the most common bariatric surgery. In 2018, LSG surgery accounted for 61.4% of all metabolic and bariatric procedures in US.^[5] Compared with LRYGB, the continuous increase of LSG may be mainly related to its advantages such as relatively simple operation, not changing the gastrointestinal physiology, few postoperative complications and good weight loss.^[6]

Compared with traditional abdominal operation, laparoscopic surgery had the advantages of less trauma, quick recovery and short hospital stay, which also had its unique complications, such as postlaparoscopic shoulder pain (PLSP), with the incidence from 35% to 80%.^[7] The incidence of PLSP in patients undergoing LSG was reported as up to 66%, and this postoperative pain may be more uncomfortable than pain of surgical site.^[8] Studies have shown that the incidence of PLSP can be decreased by reducing the pneumoperitoneum pressure, slowing down the speed of the injected gas, and using the heating gas which can reduce the stimulating effect of intraabdominal gas on the diaphragm.^[9,10] We speculated that it was not only related to the reduction of intra-abdominal pressure, but probably also to the reduction of CO₂ concentration in blood. Therefore, this study was designded to obeserve the effect of intraoperative mild hyperventilation on the incidence of PLSP after LSG, to verify the above conjecture and provide a reference for reducing the occurrence of PLSP after such surgery.

2. Materials and methods

2.1. Participants

The Consolidated Standards of Reporting Trials (CONSORT) recommendations were followed in this study.^[11] Ethical approval for this study (2022-06-030-K01) was provided by the Institutional Ethics Committee of Yingshang County Hospital of Traditional Chinese Medicine. All participants involved were informed of the proposal and gave their written, informed consent.

Eighty patients undergoing elective LSG from July 1st to December 31th, 2022 in Yingshang County Hospital of Traditional Chinese Medicine were enrolled, with American Society of Anesthesiologists (ASA) I or II, age 22 to 36. The exclusion criteria were as follows: combined mental disorder; combined cardiovascular and respiratory diseases; combined with functional insufficiency of important organs such as heart, liver, kidney and others; combined chronic diseases such as periarthritis of shoulder and cervical spondylosis; history of thoracic and abdominal surgery; history of long-term analgesic or diazepam medication; transfer laparotomy; operation time > 2 hours; intraoperative blood loss > 400 mL; intraoperative pressure of end-tidal carbon dioxide (P_ETCO₂) did not reach the expected value.

2.2. Study design

All the subjects were divided into test group (group A) and control group (group B) by random number tables generated through a computer, with 40 cases in each group.

A mild hyperventilation was used in group A with P_ETCO₂ fluctuating from 30 to 33 mm Hg, while conventional ventilation was used in group B with P_ETCO₂ 35 to 40 mm Hg during the operation. Neither observer nor subjects were aware of the grouping condition.

2.3. Sample size

Based on the results of our pre-experiment (10 participants in each group), the incidence of PLSP at 24 hours after the operation can be reduced by 20% in the test group. Power analysis showed that a reduction rate of 20% with α = 0.05 and a 10%

dropout rate within a power value of 90%, a sample size of at least 36 per group was needed. Forty samples for each group were designed in this study. Figure 1 showed the CONSORT flow diagram of the study participant’s recruitment.

Figure 1.

In this study, 80 cases were initially screened, and 3 cases were excluded (In group A, 1 case was excluded for not reaching the expected value of intraoperative P_ETCO₂; in group B, 1 case was excluded for duration of operation > 2 h, and another participant was excluded due to transfer laparotomy). In total, 39 cases in group A and 38 cases in group B were included in the statistical analysis. CONSORT = the Consolidated Standards of Reporting Trials.

2.4. Randomization

This study was conducted in Yingshang County Hospital of Traditional Chinese Medicine in the period from July 1st to December 31th, 2022. Patients were randomly assigned 2 groups. Random tables were generated using SPSS 20.0. Eighty sealed envelopes were prepared by a statistician who did not participate in the study. The study was performed with neither patients nor observers’ awareness of the group to which each patient belonged.

2.5. Interventions and outcome measures

All participants were fasting 12 hours and fasting in liquid 6 hours, and atropine (0.5 mg) was given by intramuscular injection 30 minutes before operation. After entering the operating room, peripheral venous access was opened, and invasive arterial blood pressure was monitored while radial artery puncture and catheterization after local anesthesia with 2% lidocaine was completed. Electrocardiography (ECG), heart rate (HR), pulse oximetry (SpO₂), P_ETCO₂ and bispectral index (BIS) were monitored. Induction of anesthesia: all patients received intravenous midazolam (0.03 mg/kg), propofol (1.5 mg/kg), cisatracurium (0.2 mg/kg), and fentanyl (3 μg/kg) in sequence at 5 minutes after oxygen inhalation (8 L/min) by the face mask. After 3 minutes of hand-controlled ventilation, tracheal intubation was performed and mechanical ventilation was connected. Parameter settings: mechanical ventilation mode: intermittent positive pressure ventilation (IPPV); tidal volume: 10 ml/kg (according to standard weight); respiratory rate: 12–16 times/min; fraction of inspired oxygen: 60–80%. P_ETCO₂ was maintained at 30–33 mm Hg in group A and 35–40 mm Hg in group B by adjusting the respiratory parameters. Maintaining of anesthesia: propofol and remifentanil were administrated by target-controlled infusion for plasma target concentration at 3.0 μg/mL and 3.0 ng/mL respectively, and cisatracurium was given by intravenous pump at 2 μg/kg·min meanwhile. BIS value was maintained at 40–60 intraoperatively by adjusting the dose of anesthetic. Hemodynamic stability was maintained during the intraoperative and anesthesia recovery periods. Esmolol was given intravenously at 10 mg/time when tachycardia (HR > 100 beats/min) occurred, and atropine was administrated at 0.5 mg/time if bradycardia (HR < 50 beats/min) occurred. Additionally, uradil was given intravenously at 10 mg/time during hypertension (SBP > 140 mm Hg) and ephedrine 6 mg/time during hypotension (SBP < 90 mm Hg). Cisatracurium was stopped 30 min before surgery, while propofol and remifentanil were stopped during suture. Five minutes before the surgery completed, tramadol (1 mg/kg) was given intravenously to prevent postoperative analgesia and troisetron (0.1 mg/kg) for postoperative nausea and vomiting. Salvage analgesia by ketorolac (10 mg/time) was administrated with the visual analogue scale (VAS) score > 3 during 1 week after surgery. All patients were sent to postanesthesia care unit for awakening since the operation was completed. With the Steward score > 4,^[12] they can leave the PCAU. All the operations was performed by the same group of surgeons. CO₂ was slowly blown into the abdominal cavity during the operation and maintained with pneumoperitoneum pressure of 12 mm Hg. At the end of the operation, manually press of the abdomen was given to remove residual gas.

The incidence and severity of PLSP were recorded at 12, 24, 48, 72 hours, and 1 week after surgery. The severity of PLSP was scored by VAS, with 0 as painless and 10 as unbearable severe pain.^[13] With the VAS score > 3 during 1 week after surgery, ketorolac (10 mg/time) was given and the total dose were recorded. Pain scores and remedial medication were performed by the same anesthesiologist who was unaware of the enrollment. Arterial blood gases were recorded before anesthesia induction, 20 minutes after pneumoperitoneum, during suture skin, and 24 hours after surgery. The postoperative recovery delay (>2 hours), lung injury and the occurrence of nausea and vomiting within 1 week were also recorded.

2.6. Statistics

Data analysis was performed by the SPSS 20.0 statistical software package, version 20.0 (SPSS Inc., Chicago, IL). Continuous variables were presented as mean ± SD, and differences between the 2 groups were analyzed with mutual comparison by single factor variance analysis (one-way ANOVA). Grade of ASA were ranked date which were analyzed with Wilcoxon test. Gender, the incidence of PLSP and adverse reactions were considered as categorical variables, which were analyzed with a χ² test. It was considered statistically significant since a P value < .05.

3. Results

In this study, 80 cases were initially screened, and 3 cases were excluded (In group A, 1 case was excluded for not reaching the expected value of intraoperative P_ETCO₂; in group B, 1 case was excluded for duration of operation > 2 hours, and another participant was excluded due to transfer laparotomy). In total, 39 cases in group A and 38 cases in group B were included in the statistical analysis (Fig. 1).

Participants in the 2 groups shared similar demographic characteristics (gender, age, body mass index [BMI], grade of ASA, duration of operation) (Table 1).

Table 1.

Characteristics of patients in the 2 groups.

Characteristic	Group A (n = 39)	Group B (n = 38)	P value
Age (yr)*	28.1 ± 5.2	27.6 ± 4.9	.556
Gender (M/F)†	18/21	16/22	.429
BMI (kg/m2)*	37.9 ± 4.5	36.8 ± 6.1	.733
ASA (I/II)‡	17/22	18/20	.528
Duration of operation (min)*	64.6 ± 6.7	67.9 ± 7.2	.627

ASA = American society of Anesthesiologists physical status, BMI = body mass index.

^*Values are presented as mean ± SD, mutual comparison by single factor variance analysis (one-way ANOVA).

^†Mutual comparison by χ² test.

^‡Mutual comparison by Wilcoxon test.

Compared with group B, the incidence of PLSP was significantly decreased at 12, 24, 48, 72 h, and 1 week after surgery (P < .01). Compared with 12, 24, 48 and 72 h, the incidence of PLSP at 1 week was significantly decreased (P < .01) (Table 2).

Table 2.

The occurrence of PLSP in the 2 groups.

Group	12 h	24 h	48 h	72 h	1 week
Group A (n = 39)	12 (30.8%)*,†	12 (30.8%)*,†	13 (33.3%)*,†	13 (33.3%)*,†	5 (12.8%)*
Group B (n = 38)	23 (60.5%)†	24 (63.2%)†	25 (65.8%)†	24 (63.2%)†	11 (28.9%)
P value	<.001	.002	.006	.004	<.001

Values are presented as n (%), mutual comparison by χ² test.

PLSP = postlaparoscopic shoulder pain.

^*Compared with Group B, P < .01.

^†Compared with the incidence of PLSP at 1 week after surgery, P < .01.

Compared with group B, the VAS score of PLSP was significantly decreased at 12, 24, 48, 72 hours, and 1 week after surgery (P < .01). Compared with 12, 24, 48 and 72 h, the VAS score of PLSP at 1 week was significantly decreased (P < .01) (Table 3).

Table 3.

The VAS score of PLSP in the 2 groups.

Group	12 h	24 h	48 h	72 h	1 week
Group A (n = 39)	1.8 ± 1.3*,†	2.1 ± 1.2*,†	2.0 ± 1.1*,†	1.9 ± 1.2*,†	1.0 ± 0.6*
Group B (n = 38)	3.5 ± 1.1†	3.7 ± 1.3†	3.5 ± 1.3†	3.6 ± 1.1†	1.9 ± 1.0
P value	.001	.002	.002	<.001	.003

Values are presented as mean ± SD, mutual comparison by single factor variance analysis (one-way ANOVA).

PLSP = postlaparoscopic shoulder pain, VAS = visual analogue scale.

^*Compared with Group B, P < .01.

^†Compared with the VAS score at 1 week after surgery, P <.01.

Compared with Group B, the pressure of CO₂ in arterial blood (PaCO₂) was significantly lower at 20 min after pneumoperitoneum and during suture skin in Group A (P < .05) (Table 4).

Table 4.

The arterial blood gas in the 2 groups.

Arterial blood gas		Group A (n = 39)	Group B (n = 38)	P value
Before anesthesia induction	PH	7.383 ± 0.029	7.379 ± 0.031	.703
	PaCO2 (mm Hg)	38.96 ± 5.22	39.21 ± 4.98	.837
	PaO2 (mm Hg)	87.75 ± 8.17	88.14 ± 7.74	.864
20 min after pneumoperitoneum	PH	7.356 ± 0.026	7.361 ± 0.024	.522
	PaCO2 (mm Hg)	38.56 ± 3.25*	44.85 ± 4.38	.018
	PaO2 (mm Hg)	388.62 ± 35.56	382.79 ± 38.14	.849
During suture skin	PH	7.368 ± 0.033	7.373 ± 0.029	.756
	PaCO2 (mm Hg)	37.82 ± 4.65*	43.76 ± 4.13	.026
	PaO2 (mm Hg)	392.54 ± 33.67	385.78 ± 36.33	.884
24 h after surgery	PH	7.391 ± 0.028	7.385 ± 0.032	.891
	PaCO2 (mm Hg)	39.06 ± 5.26	40.35 ± 4.91	.596
	PaO2 (mm Hg)	85.94 ± 7.57	86.67 ± 6.89	.886

Values are presented as mean ± SD, mutual comparison by single factor variance analysis (one-way ANOVA).

PaCO₂ = pressure of CO₂ in arterial blood, PaO₂ = pressure of O₂ in arterial blood, PH = Potential of hydrogen.

^*Compared with Group B, P < .05.

The total dosage of ketorolac used in group A was significantly lower than that in group B (30.7 ± 8.6 vs 63.2 ± 6.9 mg, P < .001) within 1 week after surgery. There was no significant difference of postoperative nausea and vomiting between group A and B (5 cases [12.8%] vs 4 cases [10.5%], P = .488). There were no lung injury or postoperative recovery delay occurred in both groups.

4. Discussion

Morbid obesity (BMI > 40 kg/m² or BMI > 35 kg/m² combined with other obesity-related diseases) can lead to hypertension, hyperlipidemia, diabetes, heart disease, etc., which can seriously affect people’s physical health and cause a huge social burden.^[14] As a widely used bariatric surgery, LSG was discussed in this study. Studies have shown that LSG has high safety, lasting postoperative weight loss, and can effectively alleviate the related comorbidities in morbidly obese patients, thus significantly improving the quality of life of morbidly obese patients.^[5,6,8] However, the higher incidence and severity of PLSP can affect patients’ postoperative recovery. The diversity of methods used to treat PLSP suggests that the underlying mechanism of PLSP be multifactorial and reflects its importance for the postoperative recovery. The results of this study showed that a mild intraoperative hyperventilation (controlling P_ETCO₂ at 30–33 mm Hg) reduced the incidence of PLSP within 1 week after surgery, and verified one of the possible mechanisms: carbon dioxide stimulation of the diaphragm.^[15]

4.1. Characteristics of PLSP

Li et al^[16] showed that PLSP occurred obviously within 72 hours after surgery, and sometimes lasted for 1 week, which affected patients’ postoperative quality of life.

Some studies suggested that the occurrence of PLSP be mainly related to factors such as surgical position and time, inflation speed and pressure, operation-related conditions and individual factors.^[17,18] There was some correlation between the selection of patient position and the occurrence of PLSP which might be mainly due to gravitational action of CO₂.^[19] It has been shown that the degree of intraperitoneal acidosis was positively correlated with the time of pneumoperitoneum and the pressure in the abdominal cavity. The faster of the CO₂ inflation rate, the greater of the pneumoperitoneum pressure, and the longer of the surgical time, the more likely it was to form carbonic acid, thus increasing the incidence of PLSP.^[20] In addition, the incidence and degree of PLSP also varied significantly among different types of surgery. For example, the incidence of PLSP for LSG was significantly higher than laparoscopic cholecystectomy and appendectomy.^[21] Therefore, the subjects of this study were selected as patients undergoing LSG and the observation point was 1 week after surgery. The results showed that the incidence of PLSP at 72 hours after surgery in the control group was 63.2% and 28.9% at 1 week respectively, which was basically consistent with the results of Park^[22] Moreover, individual factors such as age, weight, childbearing history, past medical history and education also had a greater influence on the incidence of PLSP.^[7]

4.2. Prevention of PLSP

PLSP was a type of referred pain caused by the stimulation of the diaphragmatic nerve endings, which was caused by a nociceptive stimulation of the surface of the diaphragm during laparoscopy.^[18] Therefore, most of the techniques used to prevent PLSP or to reduce the incidence were based on reducing physical or chemical stimulation on the surface of the diaphragm. Studies have shown that discharging the remaining intraperitoneal gas by using passive drainage or active aspiration at the end of the procedure can reduce the CO₂ in the peritoneal cavity,^[9] applying lung compmanipulation can squeeze out the gas,^[23] using gas heating, lowing pneumoperitoneum pressure,^[10] low inflation rate and even using gas-free laparoscopy can reduce body irritation, all of which can reduce the incidence of PLSP. Furthermore, PLSP was reduced by inhibition of pain signals itself with anti-inflammatory agents, such as local anesthetic for surface of diaphragm at the beginning or the end of surgery,^[24] intraperitoneal infusion of dexmedetomidine, bupivacaine or hydrocortisone,^[25] and intraperitoneal or intrathecal injection of clonidine.^[26] Kim et al^[9] suggested that the intraoperative use of low-pressure laparoscopy reduce the input of physical and chemical stimuli, which was the most effective strategy to reduce the morbidity of PLSP. In this study, the incidence and severity of PLSP were successfully reduced by the use of mild intraoperative hyperventilation, which might be related to reducing the concentration of carbonic acid in the diaphragmatic tissue by lowing of CO₂ in the blood, thus reducing the stimulation of the diaphragmatic nerve endings.^[27] According to the previous study,^[28] the P_ETCO2 value after mild hyperventilation in this study was designed to lower than the normal value, but still within the clinical safety limits, without crossing with the P_ETCO2 value of the control group. In the study, due to artificial regulation, PaCO₂ was lower in Group A. However, the results of arterial blood gas at different points were not abnormal, and the PH value were not statistically significant, which also indicated that the reduction of P_ETCO₂ value after mild hyperventilation did not affect the acid-base balance of the patients.

Due to the reduction in the incidence and severity of PLSP, the amount of postoperative analgesic drug (ketorolac) was also significantly decreased in the test group. The study of Martinez et al^[29] has showed that reducing the amount of postoperative analgesic drugs can reduce the related adverse reactions such as nausea, vomiting, respiratory depression, skin itching and so on. There was no significant difference in the incidence of postoperative nausea and vomiting, lung injury and recovery delay between the 2 groups in this study, which might be related to ketorolac being one of the non-steroidal analgesics, while the opioid was used in the above study. The result also indicated that the different levels of P_ETCO₂ in this study did not affect the occurrence of these adverse reactions.

4.3. Limitations

There are some limitations in the study. Due to the different settings of P_ETCO₂, the investigator was not blinded in the study, but who did not involve in recording the data. In addition, difference between the occurrence of left and right shoulder pain was not analyzed, and pain of other site such as epigastric pain caused by local CO₂ between diaphragm and liver was not assessed as well.

5. Conclusions

Intraoperative mild hyperventilation helps to reduce the incidence and severity of PLSP without increasing related adverse effects in patients undergoing LSG.

The method is safe and effective, which can provide a reference for the clinical prevention of the occurrence of PLSP.

Author contributions

Data curation: Chaotao Fan.

Formal analysis: Chaotao Fan, Bin Ling.

Investigation: Chaojie Yang, Peng Rong.

Methodology: Chaojie Yang, Peng Rong.

Project administration: Jian Zhang.

Supervision: Jian Zhang, Wei Wang.

Writing – original draft: Chaojie Yang.

Writing – review & editing: Wei Wang.