Pulmonary recruitment maneuver reduces pain after laparoscopic bariatric surgery: a randomized controlled clinical trial

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1 Surgery for Obesity and Related Diseases ] (2017) Original article Pulmonary recruitment maneuver reduces pain after laparoscopic bariatric surgery: a randomized controlled clinical trial Ebba Kihlstedt Pasquier, M.D. *, Ellen Andersson, M.D., Ph.D. Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Norrköping, Sweden Received July 2, 2017; accepted November 15, 2017 Abstract Keywords: Background: Pulmonary recruitment maneuver (PRM) at the end of laparoscopic gynecologic surgery has been shown to reduce postoperative pain. This prospective, randomized, controlled clinical trial aimed to investigate postoperative pain (primary endpoint) and nausea when performing a ventilator-piloted PRM at the end of laparoscopic bariatric surgery. Settings: A secondary-level public hospital in Sweden. Methods: After giving written consent, patients undergoing elective laparoscopic bariatric surgery were randomized to receive routine exsufflation (control group) or a ventilator-piloted PRM to remove residual carbon dioxide from the abdomen at the end of surgery. Pain and nausea intensities were recorded at 4, 12, 24, 36, and 48 hours after surgery using a questionnaire with numeric rating scales. Postoperative consumption of analgesics and antiemetics was also evaluated. Results: There were 150 randomly assigned patients recruited, 79 to PRM intervention and 71 controls. Pain intensity was significantly lower in the PRM group than in the control group 24 hours postoperatively (numeric rating scale 2 [1 3] versus 3 [2 5]; P ¼.002). Pain during the first 24 hours did not increase in the PRM group as it did in the control group (P ¼.045). Opioid requirements were significantly lower in the PRM group than in the control group (5.0 mg [2 10] versus 9.0 mg [5 15]; P ¼.025). The PRM did not affect incidence or intensity of nausea and vomiting. Conclusions: A ventilator-piloted PRM reduced postoperative pain intensity and opioid requirement after laparoscopic bariatric surgery. The heterogeneity of the study population and the large number of hospital staff involved indicate good generalizability of the results. (Surg Obes Relat Dis 2017;]:00 00.) r 2017 American Society for Metabolic and Bariatric Surgery. This is an open access article under the CC BY-NC-ND license ( Pulmonary recruitment; Laparoscopy; Postoperative pain; Postoperative nausea; Bariatric surgery Patients undergoing a laparoscopic intervention usually experience postoperative pain. The pain may persist for several days and may be intense, not only in the abdomen but also in the shoulders. Other symptoms commonly The study was supported by ALF grants from Region Östergötland, Sweden. * Correspondence: Ebba Kihlstedt Pasquier, M.D., Department of Surgery, Vrinnevi Hospital, Gamla Övägen 25, Norrköping, Sweden. kihlstedt@gmail.com affecting patients after laparoscopic surgery are nausea and vomiting [1 5]. Apart from the surgical trauma and the intra-abdominal pressure applied during the procedure, postlaparoscopic abdominal and shoulder pain are believed to be related to carbon dioxide (CO 2 ) trapped in the abdomen. This entrapment of gas may lead to direct irritation, local acidosis, and stretching of the diaphragm. The shoulder pain is believed to be caused by gas-induced irritation of the phrenic nerve, leading to referred pain in the shoulder. One method that seems to decrease postlaparoscopic pain is the removal of /r 2017 American Society for Metabolic and Bariatric Surgery. This is an open access article under the CC BY-NC-ND license (

2 2 E. K. Pasquier and E. Andersson / Surgery for Obesity and Related Diseases ] (2017) residual CO 2 by applying a pulmonary recruitment maneuver (PRM) at the end of the surgical procedure [1 4,6 8]. Inflation of the lungs and descent of the diaphragm during the PRM causes the intra-abdominal pressure to increase, mechanically facilitating exsufflation of intra-abdominal CO 2. Pneumoperitoneum can result in systemic absorption of CO 2, especially in the morbidly obese, because the intraabdominal gas pressure used when performing laparoscopy is higher than in patients with a normal body habitus [9]. In a recent study, mild intraoperative hypercarbia (end-tidal CO mm Hg) was associated with a significant decrease in postoperative nausea and vomiting [10]. Could a PRM increase postoperative nausea and vomiting? Previous studies have not shown any correlation between PRM and incidence of nausea in patients with a normal body habitus [1 3,7]. To our knowledge, no previous study has been performed on the effect of PRM on postoperative pain and nausea in patients undergoing bariatric surgery. This study tests the hypothesis that PRM reduces the intensity of postoperative pain (primary endpoint) and investigates any effect on postoperative nausea (secondary endpoint) in the morbidly obese person undergoing laparoscopic bariatric surgery. Methods The study was designed as a prospective, randomized, controlled, blinded, parallel group, single-center, clinical trial. The participants, the postoperative staff, the doctor discharging the patients, and the investigator eventually collecting and registering data were all blinded to group allocation. Participants were recruited at Vrinnevi Hospital, Sweden. The Regional Ethical Review Board in Linköping, Sweden approved all study procedures (Dnr 2014/120-31). The trial was registered at registration number: NCT Patient recruitment and randomization Inclusion criteria was as follows: adults (aged 418 yr); body mass index 35 kg/m 2 ; American Society of Anesthesiologists physical status classification I to II, including body mass index 40 kg/m 2 ; and undergoing elective laparoscopic bariatric surgery. Written consent was obtained. Criteria for exclusion from analysis were conversion to open surgery and complications classified as Clavien-Dindo grade II [11]. Patients scheduled for elective laparoscopic bariatric surgery were consecutively enrolled into the study between November 2014 and May Using a computerized method, participants were randomized to 1 of 2 equally sized groups: intervention with PRM or control. An independent statistician at Forum Östergötland generated the randomization list in blocks of 2. The block size was kept secret to the researchers until the end of the study. After randomization, allocation instructions were placed in opaque, sealed, and numbered envelopes. As each participant was about to be transferred to theater, the next sealed envelope in turn was sent together with the patient s surgical notes. The anesthetic staff opened the envelope during the operation and, depending on group allocation, performed PRM or ordinary ventilation during the exsufflation process at the end of the surgical procedure. Preoperatively, the participants filled out a form with information about age, weight, height, body mass index, sex, preoperative pain, and analgesic consumption, and whether they had prior abdominal surgery. Minimum 6 weeks of nonsmoking before surgery was a prerequisite for the operation. Registered operative and postoperative variables included type of surgery and anesthesia, duration of operation, amount of blood loss, complications, given medication, and the duration of postoperative hospital stay. Surgery and study intervention The surgical procedure (laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy) was performed according to routine clinical standards by 1 of 6 consulting surgeons skilled in the technique. CO 2 was introduced through a Veress needle placed under the left thoracic cage at the start of the operation and later through one of four 12-mm ports inserted in the upper abdominal area. A Nathanson liver retractor was used. The gas pressure was set to maximum 16 mm Hg. A total of 40 ml bupivacaine hydrochloride 5 mg/ml with epinephrine 5 ug/ml was infiltrated subcutaneously at the port sites before insertion of the trocars. General anesthesia was managed by a consultant anesthesiologist and a nurse specialized in anesthesiology. Induction was with remifentanil or alfentanil in combination with thiopental or propofol, and maintained with intravenous remifentanil and propofol or a combination of remifentanil and sevoflurane in oxygenenriched air, the doses depending on the patient s requirements. The ventilator mode was set to pressure regulated volume control. Vital signs were monitored according to standard clinical practice. After surgery, the skin openings were adapted with staples. The fascia at the trocar sites was not sutured. In the control group, residual CO 2 was evacuated by exsufflation through the open sleeve valves of 2 ports in the upper part of the abdomen, with the surgeon applying gentle abdominal pressure. Patients in the intervention group had CO 2 exsufflated in the same way, but also underwent a PRM before removal of the ports, using the ventilator (GE Datex-Ohmeda Aisys, Madison, WI, United States) according to a specific protocol developed by 2 of the hospital s consultant anesthesiologists (Fig. 1). During 1 minute, the ventilator mode was changed to pressurecontrolled ventilation. The patient received 6 breaths with

3 PRM Reduces Pain After Laparoscopy / Surgery for Obesity and Related Diseases ] (2017) A standardized numeric rating scale (NRS) range 0 (no pain/nausea) to 10 (worst imaginable pain/nausea) was used to measure pain and nausea, respectively, at rest [13]. Statistical analysis Fig. 1. Protocol for pulmonary recruitment maneuver (PRM) during anesthesia. O 2 ¼ oxygen; Fi ¼ fraction of inspired; Sev ¼ sevoflurane. a positive inspiratory pressure of 20 cm H 2 O and a positive end-expiratory pressure of 20 cm H 2 O, giving a total pressure of 40 cm H 2 O. The duration was chosen to match the number of breaths used to perform PRM in previous studies. Because CO 2 is heavier than air [12], all patients were in the supine position to avoid retention of CO 2 in either the pelvis or between the liver and the diaphragm. The surgical staff in both groups did not remove the ports until the anesthetic staff confirmed that the PRM/control procedure had been completed. Drugs All participants preoperatively received 1 to 1.3 g paracetamol orally. Toward the end of the operation, patients were given 30 mg ketorolac (unless contraindication) and morphine intravenously (IV); the dose of the latter was registered for follow-up. All patients received antiemetic treatment with.5 mg droperidol and 4 mg betamethasone IV. Those with a history of postoperative nausea and vomiting also received 4 mg ondansetron IV. For postoperative analgesia, all participants received 1 g paracetamol 4 times a day. Intravenous opioids were given as required in the postanesthesia care unit. Thereafter, in the surgical ward, a 5 mg immediate-release oxycodone capsule was given on request. Participants suffering from nausea received ondansetron IV as required. The doses given were registered for follow-up. Questionnaire After their operation, participants were asked to answer a questionnaire on 5 occasions during the first 48 hours after surgery. The questionnaires were divided into 2 parts. Part 1, including data at 4, 12, and 24 hours postoperatively, was returned when the participant was discharged from the surgical ward. Part 2, including data at 36 and 48 hours postoperatively, was either handed in to the ward or returned by post in a stamped and addressed envelope. Assuming a clinically relevant difference in mean pain intensity score at a given occasion of 2 points between intervention and control groups, with a standard deviation of 3.5 points (based on results from Tsai et al. [2,3]), it was calculated that the sample size required for adequate power was 69 participants per group, using a 2-tailed Wilcoxon Mann-Whitney U test (90% power and α.05 with a 2 significance level). To allow for loss to follow-up, we decided to include 100 patients in each group. Differences between groups were compared using χ 2 test for binominal variables, while 2-sample t test (for normally distributed data) or Mann-Whitney U test (specified in the tables) were used to compare continuous variables. Analysis of variance (ANOVA) for repeated measures was used to detect any difference in NRS scores over time. A perprotocol analysis was performed. Results are presented as median (interquartile range) or numbers with percentages, unless stated otherwise. Statistical significance was defined as P o.05. SPSS 23.0 (SPSS Inc., Chicago, IL) was used for all statistical analyses. Results From November 2014 to May 2016, 200 participants were included and randomized, 100 to PRM and 100 to the control group. Fifty patients were later excluded. After randomization, 7 patients who should not have been included were excluded from the study. Of these patients, 2 had been classified as American Society of Anesthesiologists III. Five participants had 41 surgical intervention planned on the same occasion. Of those excluded from analysis, 10 suffered a complication: 2 converted to open surgery; 2 required reoperation; 2 needed blood transfusion; 1 operation was cancelled because of extensive adhesions; 1 suffered an intestinal rift requiring suture and needed an umbilical trocar because of adhesions where the trocar would normally have been inserted; 1 received a tube drainage; 1 suffered intra-abdominal bleeding postoperatively (detected by computed tomography performed because of pain, tachycardia, and a fall in hemoglobin) and remained an extra day on the surgical ward for observation. The remaining 33 who were excluded had not returned any part of the questionnaire (Fig. 2). This resulted in 150 randomized participants with sufficient data for analysis, 133 with complete data and 17 with partially complete data (79 participants in the PRM group and 71 in the control group). There was no significant difference between excluded patients and those with analyzable data regarding randomization to control or

4 4 E. K. Pasquier and E. Andersson / Surgery for Obesity and Related Diseases ] (2017) Fig. 2. Flow chart of inclusion, exclusion, and group allocation. PRM ¼ pulmonary recruitment maneuver; ASA ¼ American society of anesthesiologists physical status. intervention group (P ¼.327). Age was the only parameter that differed between excluded patients and participants, the excluded patients being slightly younger (P ¼.038). With regard to demographic, surgical, and anesthesiologic variables, no significant differences were detected between the groups (Tables 1 and 2). No pulmonary complication due to PRM was observed. In both groups, NRS pain scores varied significantly during the 48-hour postoperative period (P o.001; ANOVA), pain being most intense during the first 24 hours after surgery. The variation in pain score over time was significantly lower in the intervention group 4 to 24 hours Table 1 Preoperative patient characteristics Patient characteristic Median (IQR) or number (%) PRM Control Sex ratio (female:male) 67 (84.8%): 12 (15.2%) 54 (76.0%): 17 (24.0%) Age, yr 47 (34 53) 44 (32 51) BMI, kg/m 2 38 (36 42) 38 (36 42) BMI 40 kg/m 2 32 (41%) 25 (35%) Previous abdominal surgery 39 (49.4%) 27 (38.0%) Fibromyalgia 7 (8.9%) 5 (7.0%) Chronic pain 24 (30.4%) 18 (25.3%) Regular opioid * consumption 3 (3.8%) 1 (1.4%) IQR ¼ interquartile range; PRM ¼ pulmonary recruitment maneuver; BMI ¼ body mass index. Opioid: tramadol tablet or codeine tablet. postoperatively (P =.045; ANOVA) (Fig. 3). At 24 hours, when the NRS pain score peaked in the control group, pain was significantly lower in the intervention group (3 [2 5] versus 2 [1 3]; P ¼.002) (Table 3). There was no significant difference in overall prevalence of pain (NRS 1 10), which, for the population as a whole, varied between a maximum of 91% at 24 hours (PRM 88.6% versus control 92.5%; P ¼.422) and a minimum of 74% at 48 hours (PRM 74.6% versus control 73.4%; P ¼.873). Patients in the control group consumed a significantly higher amount of opioids during their stay in hospital compared with the PRM group (9.0 [5 15] versus 5.0 [2 10]; P ¼.025) (Table 4). After discharge from hospital, there was no difference in oral analgesic consumption (paracetamol and/or oxycodone) between the groups; 90% of the population still medicated at 36 hours (PRM 90.4% versus control 89.1%; P ¼.795) and 69% at 48 hours (PRM 69.4% versus control 68.8%; P ¼.930). To avoid misinterpretation, doses taken after discharge were not analyzed. There was no significant difference between the groups regarding the incidence of constant or intermittent nausea. Of all participants, 57% experienced nausea at rest 4 hours after surgery, (NRS 1 10; PRM 55.8% versus control 58.6%; P ¼.739). The incidence subsequently fell. Approximately 60% of patients initially experienced intermittent episodes of nausea (PRM 61.8% versus control 61.2%; P ¼.937), 5% constant nausea (PRM 3.8% versus control 7.1%; P ¼.366), and roughly 10% vomited at some

5 PRM Reduces Pain After Laparoscopy / Surgery for Obesity and Related Diseases ] (2017) Table 2 Operative variables Operative variable Median (IQR) or number (%) P * PRM Control PRM versus control LRYGB:LSG 74 (93.7%):5 (6.3%) 68 (95.8%):3 (4.2%).567 Duration of surgery, hr:min:s 1:08:00 (0:56 1:25) 1:04:00 (0:55 1:15).070 Anesthesia induction (remifentanil:alfentanil) 60 (75.9%):19 (24.1%) 60 (84.5%):11 (15.5%).191 Anesthesia maintenance (total IV:inhalation þ IV) 25 (31.6%):54 (68.4%) 29 (40.8%):42 (59.2%).241 Complication 3 (3.8%) 3 (4.2%).894 Estimated blood loss, ml 0 (0 0) 0 (0 0).151 Betamethasone 4 mg 79 (100.0%) 71 (100.0%).999 Droperidol 0.5 mg 76 (96.2 %) 69 (97.2%).738 Ondansetron 4 mg 11 (13.%) 10 (14.1%).977 Ketorolac 30 mg 63 (79.7%) 57 (80.3%).935 Morphine 74 (93.7%) 68 (95.8%).567 Morphine dose, mg 10 (7 10) 10 (8.5 10).089 Local anesthetic 78 (98.7 %) 71 (100.0 %).342 IQR ¼ interquartile range; PRM ¼ pulmonary recruitment maneuver; LRYGB ¼ laparoscopic Roux-en-Y gastric bypass; LSG ¼ laparoscopic sleeve gastrectomy; IV ¼ intravenous; total IV ¼ remifentanilþpropofol; inhalationþiv: sevofluraneþremifentanil. χ 2 test for binominal variables; t test or Mann Whitney U test for continuous variables. point during the first 12 hours (PRM 10.1% versus control 12.9%; P ¼.601). The postoperative NRS nausea score was generally low. No significant difference was seen between the groups at any time. The highest scores occurred 4 hours postoperatively, the median nausea score being 1 (0 3) in both groups (P ¼.779; Mann-Whitney U test). Nausea intensity decreased significantly over time in both groups (P o.001; ANOVA). Discussion In this randomized, controlled trial, a PRM significantly reduced overall postoperative pain after laparoscopic bariatric surgery. Apart from a study by Khanna et al. [6], including patients undergoing laparoscopic inguinal hernia surgery and laparoscopic cholecystectomy, previous studies on the effect of PRM on postoperative pain after laparoscopic surgery have been performed on patients undergoing gynecologic surgery [1 4,7]. The beneficial effect of PRM after laparoscopy in the present study is consistent with previous studies. This study, however, solely analyzed the effect of PRM in patients undergoing upper abdominal surgery (i.e., laparoscopic bariatric surgery). Patients in the intervention group underwent a ventilatorpiloted PRM. This means that the positive inspiratory pressure was the same for each patient (40 cm H 2 O) but that the ventilator individually adapted the size of the breath. This enables a PRM that is equal for every patient in terms of pressure, making it easier to evaluate the results. In previous studies, the PRM was performed manually, with a maximum inspiratory pressure of 40 cm H 2 O [4,7] or Table 3 Postoperative pain score, numeric rating scale 0 to 10 Hr after surgery Median (IQR) P * PRM Control PRM versus control Fig. 3. Development of pain intensity over the first 48 hours after surgery. Mean NRS score differed significantly between the groups 24 hours after surgery (2.28 ± 1.65 in the PRM group versus 3.31 ± 2.09 in the control group; P ¼.002). PRM ¼ pulmonary recruitment maneuver; NRS ¼ numeric rating scale. 4hr 3(1 3) 2 (1 4) hr 2 (1 4) 3 (1 4) hr 2 (1 3) 3 (2 5) hr 2 (1 3) 2 (1 4) hr 1 (0 2) 1 (0 2.75).666 IQR ¼ interquartile range; PRM ¼ pulmonary recruitment maneuver. Mann-Whitney U-test

6 6 E. K. Pasquier and E. Andersson / Surgery for Obesity and Related Diseases ] (2017) Table 4 Postoperative medication and hospital stay Postoperative variable Median (IQR) or number (%) 60 cm H 2 O [1 3,6]. Because the pulmonary pressure when coughing or sneezing usually rises to 4100 cm H 2 O, the risk of pneumothorax at 40 cm H 2 O was considered negligible, at least in persons not suffering from severe lung disease [14]. The technique was easy to monitor, and no adverse effect was observed. Furthermore, the participants in this study were kept in the supine position during the PRM or control procedure, in the belief that this would be a both safe and efficient position. The supine position does not have hemodynamic effects, such as the Trendelenburg and reversed Trendelenburg positions [15]. In previous studies, the participants were kept in the Trendelenburg position [1 4,6,7]. We did not compare different positions but conclude that the supine position when performing a PRM is just as efficient to lower pain intensity after laparoscopy. In both groups in the present study, pain was most intense during the first 24 hours after surgery. However, there was a significant difference between the groups, in favor of the PRM group, in pain development over these 24 hours. While the intensity of pain in the PRM group was fairly constant over the first 36 hours after surgery, a peak with a higher pain score was seen at 24 hours in the control group. Compared with the control group, 1 minute of ventilator-piloted PRM significantly reduced NRS pain scores 24 hours after surgery. This is consistent with the results of the only previous study that has analyzed postlaparoscopic overall pain, showing that PRM significantly lowered pain at 24 and 48 hours [6]. This indicates that the pain-reducing effect of the maneuver is effective when it is most needed. We also found the effect to be short lasting (~30 hr), which is in agreement with other studies [2,3,7]. The pain experienced by patients in both our groups, especially the control group, was generally lower than in P * PRM Control PRM versus control Paracetamol 1 g/6 hr 79 (100.0%) 69 (97.2%).133 IV opioid, mg 2.5 (0 5) 5.0 (0 9).239 Oxycodone tablet, mg 0.0 (0 5) 5.0 (0 10).063 Total opioid postoperative, mg 5.0 (2 10) 9.0 (5 15).025 IV ondansetron, mg 4.0 (0-4) 2.0 (0 4).815 Hospital stay, d 1 (1 1) 1 (1 1).216 IQR ¼ interquartile range; PRM ¼ pulmonary recruitment maneuver; IV ¼ intravenous. t test IV opioid: morphine or ketobemidone (1:1). Mann-Whitney U-test Total opioid (IV morphine equivalent dose): IV opioid and oral oxycodone (1:1) [18 20]. other studies evaluating abdominal pain after laparoscopy. The difference in NRS scores between the groups at 24 hours was of similar magnitude as in previous studies [8]. An explanation for the lower NRS scores in our groups could be that they were evaluated at rest. In the studies by Phelps et al. [1] and Liu et al. [7] a significant number of participants described shoulder pain as being related to position or motion. Inclusion of pain upon movement would naturally have led to a higher incidence and intensity of pain in our study, but it would have been more difficult to compare the groups. Even though the postoperative pain was well controlled in both groups, the control group required a significantly higher amount of opioids than the intervention group. This finding strengthens our observation that patients in the control group suffered more pain than those in the intervention group. Sharami et al. [4] showed a similar difference using diclofenac. Intermittent nausea was common in the immediate postoperative period, although this receded after 4 hours. The incidence was comparable to that seen in previous studies (30% 70%) [1 3,5,7]. The results show a generally low intensity of nausea. There were no differences between the groups regarding incidence of nausea or nausea NRS score, which indicates that PRM does not affect nausea. Surgery in the PRM group took a few minutes longer, but the difference was not statistically significant. This was also the case in 3 previous studies [1,2,4], while the opposite occurred in 2 [3,7]. In no study was the difference significant, leading us to conclude that the time it takes to perform a PRM at the end of surgery is negligible. Unfortunately, we did not achieve standardization of the anesthetic management. However, there was no statistically significant difference between the PRM and control group regarding anesthetic regimen. The most common induction combination was remifentanil and propofol. Induction with alfentanil and thiopental is by local tradition used for patients with gastrointestinal reflux. Remifentanil and alfentanil, which provided the analgesic effects, have rapid onset of action and short terminal half-lives [16]. Their induction effect ought not to be longer than the surgery itself. Alfentanils duration of activity is o10 to 24 minutes after a single dose [16,17]. To maintain anesthesia, remifentanil was the analgesic drug of choice. It has a terminal elimination half-life of only 6 to 12 minutes, independent of renal and hepatic function [16]. All the analgesic and hypnotic drugs have nausea and vomiting as common side effects. Altogether, we do not believe the differences in anesthetic regimen have influenced the experience of postoperative pain or nausea. In contrast to previous studies on this subject, our study involved many members of the hospital staff. Furthermore, the study population was quite heterogeneous regarding age, sex, and health status. These differences may be considered as weaknesses of the present study. However,

7 PRM Reduces Pain After Laparoscopy / Surgery for Obesity and Related Diseases ] (2017) because our study population was large, the procedure standardized, and the results obtained are similar to previous studies, we believe this indicates good generalizability. Conclusions The results of this study suggest that a 1-minute ventilator-piloted PRM significantly reduces pain after laparoscopic upper gastrointestinal surgery, and decreases the need for opioids. The maneuver is safe, inexpensive, and therefore easily implemented in day-to-day clinical practice. Without reason to fear negative effects of the maneuver, we suggest that a ventilator-piloted PRM should be performed routinely at the end of intra-abdominal laparoscopic procedures, at least in patients classified as American Society of Anesthesiologists I to II, including those with morbid obesity. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. Acknowledgments The authors thank anesthesiologists L. Abildgaard and H. Krook (Vrinnevi Hospital, Norrkoping, Sweden) for their support and help in designing a ventilator-piloted PRM protocol. They also thank Mats Fredriksson (statistician, Forum Östergötland, Linkoping University Hospital, Sweden) for his assistance with randomization and statistical analysis and all hospital staff involved in this study for their work and kind support. References [1] Phelps P, Cakmakkaya OS, Apfel CC, Radke OC. A simple clinical maneuver to reduce laparoscopy-induced shoulder pain: a randomized controlled trial. Obstet Gynecol 2008;111(5): [2] Tsai HW, Chen YJ, Ho CM, et al. Maneuvers to decrease laparoscopy-induced shoulder and upper abdominal pain: a randomized controlled study. Arch Surg 2011;146(12): [3] Tsai HW, Wang PH, Yen MS, Chao KC, Hsu TF, Chen YJ. Prevention of postlaparoscopic shoulder and upper abdominal pain: a randomized controlled trial. 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