Strengths and limitations of this study
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A monocentre, prospective, double-blind, randomised controlled trial with an appropriate sample size has been conducted at a tertiary hospital.
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The modified opioid-sparing anaesthesia protocol is employed to perform laparoscopic bariatric surgery.
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The postoperative quality of recovery (item 15) is applied in patients undergoing laparoscopic bariatric surgery.
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This single-centre nature is the potential for biased results in other settings.
Introduction
Obesity is a significant global health issue that is closely linked to an elevated risk of various adverse health outcomes including diabetes, dyslipidaemia, stroke, cardiovascular disease, certain types of cancers, osteoarthritis and mental disorder.1 Laparoscopic bariatric surgery (LBS) is recognised as a prompt, efficient and safe intervention for managing obesity and associated metabolic disorders. The two most commonly performed bariatric surgeries are sleeve gastrectomy and Roux-en-Y gastric bypass.2 Short-term complications such as postoperative nausea and vomiting (PONV) and pain following LBS can lead to reduced sleep quality, delayed physical activity, prolonged hospitalisation, diminished postoperative recovery quality and delayed rehabilitation.3 4
The implementation of enhanced recovery after surgery (ERAS) in LBS and medical care in clinical settings has led to a growing focus on patient-reported outcome measures.3 5 6 Quality of recovery item 15 (QoR-15) serves as a crucial assessment tool for evaluating the early postoperative health status of patients undergoing LBS, offering a patient-centred perspective on various aspects of the recovery process, including pain management, psychological well-being and emotional state.7
Opioid-free anaesthesia (OFA) or opioid-sparing anaesthesia (OSA) strategies employ multimodal analgesic approaches that integrate regional blocks, dexmedetomidine, ketamine/esketamine, magnesium sulphate, lidocaine and non-steroidal anti-inflammatory drugs (NSAIDs).8 Guidelines for ERAS after LBS suggest that OFA/OSA protocols can effectively reduce postoperative pain, opioid consumption and opioid-related complications such as respiratory depression, pruritus and nausea.3 8 Some studies have indicated an increased incidence of bradycardia and hypoxaemia in patients under OFA, highlighting the need for a more balanced anaesthesia approach in clinical practice.9–11
However, traditionally, opioids play a central role in perioperative pain management, OFA/OSA approaches rely on alternative medications like NSAIDs, dexmedetomidine and esketamine, which may pose risks such as gastrointestinal issues, bradycardia and hallucinations. In clinical settings, the anaesthetic and analgesic components of OFA/OSA (a multimodal analgesia ‘cocktail’ approach) vary among different institutions, and the benefits as well as potential risks of a proposed modified opioid-sparing anaesthesia (MOSA) for patients undergoing LBS remain inconclusive.
Methods and analysis
Study design and setting
This single-centre, randomised, double-blind, controlled trial is aimed at investigating the effect of MOSA on QoR-15 in patients undergoing LBS. The study is carried out at Yan’an Hospital of Kunming City, Kunming, China. This study was reviewed and approved by the Institutional Review Board of this hospital (approval No. 2023-240-01). All participants will provide written informed consent before enrolment. This trial was registered at http://www.chictr.org.cn on 19 December 2023. This protocol follows the guidelines of the Standard Protocol Items: Recommendations for Interventional Trials statement.12 The flowchart and schedule of this trial are presented in figure 1 and tables 1 and 2, respectively.
Trial flow chart. MOSA, modified opioid sparing anaesthesia; OBA, opioid-based anaesthesia.
Details in the protocol for MOSA and OBA
Summary of study assessments and procedures
Participants
Inclusion criteria
Inclusion criteria are as follows: aged at least 18 years; American Society of Anesthesiologists physical status I–III; LBS under general anaesthesia; ability to provide written informed consent.
Exclusion criteria
Exclusion criteria are as follows: patients with currently pregnant or breastfeeding; contraindications or allergic reactions to medications such as esketamine, dexmedetomidine and lidocaine; severe mental disorders like schizophrenia, depression and dementia; a history of substance abuse involving alcohol, opioids or other psychotropic medications; unable to comply with study requirements due to reasons such as language comprehension disorders, hearing impairments or mental illness; preoperative admission to the intensive care unit (ICU); participants concurrently enrolled in other research projects.
Drop out criteria
Unplanned admission to the ICU after surgery; temporary changes in the surgical procedure under anaesthesia; withdrawal from the study at any time point.
Recruitment
Patients for elective LBS will undergo eligibility screening 1-day before the scheduled operation. The site investigator will identify consecutive eligible patients based on the specified criteria. Each patient will receive comprehensive information about their role in the study and will be assured that their personal information will be kept strictly confidential.
Informed consent
Based on these criteria, eligible patients will be enrolled after providing informed written consent to the investigator.
Randomisation and blinding
On obtaining informed consent, the participants will be allocated into either the intervention group (MOSA group) or the control group (OBA group) in a ratio of 1:1 through randomisation. This random allocation procedure will be carried out as close as possible to the commencement of the surgical procedure. The randomisation sequence will be developed and administered by impartial professionals who will ensure the allocation remains concealed. Additionally, all individuals involved in the study will be kept unaware of the randomisation outcomes. The group assignments will be sealed in opaque envelopes with visible serial numbers, which will be provided to the anaesthesiologist prior to the initiation of anaesthesia.
The anaesthesiology team will be blinded to the allocation group, ensuring that they are not aware of which group a patient has been assigned to. Patients will also be kept uninformed of their group assignment and the specific aesthetic agents administered during surgery. The individual responsible for performing anaesthesia will not be involved in data collection, postoperative monitoring or assessment. Subsequent postoperative monitoring and evaluations will be carried out by a separate individual who is also blinded to the patients’ group assignment. The assessor will be strictly prohibited from accessing the medical and anaesthesia records of the patients until all follow-up visits have been completed. Furthermore, the assessor will be restricted from conducting any statistical analysis.
Standard anaesthetic and analgesic management
Preoperative evaluation
The day prior to the surgical procedure, every patient participated in a customary clinical consultation. The criteria for inclusion and exclusion were employed to determine suitable candidates for this research. Suitable candidates will be provided with standardised ERAS education. Consent will be sought with due diligence, and essential patient data will be recorded. The adjusted body weight of each patient was calculated prior to induction of general anaesthesia. Medication dosages and tidal volumes are in accordance with the adjusted body weight. The adjusted body weight was determined using the formula: adjusted body weight=ideal body weight + 0.4 × (current body weight – ideal body weight).
Intraoperative ventilation strategy
All patients will receive a lung-protective ventilation strategy, with volume-controlled mechanical ventilation being initiated after tracheal intubation. Tidal volume will be set at 6–8 mL/kg, positive end-expiratory pressure at 5–8 cm H2O and ventilator frequency adjusted to maintain partial pressure of end-tidal carbon dioxide within the range of 35–45 mm Hg. The fraction of inspired oxygen will be maintained between 0.4 and 1.0 to maintain pulse oximetry levels over 93%. Recruitment manoeuvres will be conducted after tracheal intubation and subsequently every 30 min until the end of the procedure.
Intraoperative management
The anaesthesiologist will administer ephedrine, phenylephrine and/or norepinephrine as necessary to closely regulate the patient’s blood pressure within a range of 80%–120% of the baseline. Goal-oriented fluid therapy may be employed during operation for effective fluid management. Patients will be provided with a warming blanket to help sustain a nasopharyngeal temperature of (36–37)°C.
Postoperative management
After the procedures, all individuals were transferred to the post-anaesthesia care unit (PACU) for tracheal extubation under the supervision of attending anaesthesiologists. Without contraindications, a dose of 1.0 mg of neostigmine and 0.5 mg of atropine was employed to counteract any residual neuromuscular blockade. Subsequently, a patient-controlled intravenous analgesia regimen was initiated, consisting of nalbuphine at a dose of 0.8 mg/kg (Max 80 mg), dexmedetomidine at a dose of 1.5 µg/kg (Max 100 µg) and ondansetron at a dose of 16 mg, with a total volume of 100 mL, delivered through a continuous infusion at a rate of 1.0 mL/hours over a period of 48 hours. The self-administration capacity was set at 2 mL with a lockout interval of 30 min. Pain levels at rest and during movement were assessed using a Numerical Rating Scale (NRS) ranging from 0 to 10 (zero for ‘no pain’, 10 for ‘pain as bad as you can imagine’ or ‘worst pain imaginable’). When the patient reported an NRS score of 4 or higher, nalbuphine at a dose of 0.1 mg/kg was administered intravenously as rescue analgesia.
Interventions
The study interventions were outlined in table 1, with both groups receiving local infiltration anaesthesia consisting of 0.375% ropivacaine at a volume of 40 mL prior to the surgical procedure. In the MOSA group, anaesthesia induction involved the administration of dexmedetomidine at a dosage of 0.5 µg/kg over 10 min, esketamine at 0.3 mg/kg, lidocaine at 1.5 mg/kg (up to a maximum of 100 mg), midazolam at 2 mg, dexamethasone at 0.1 mg/kg, propofol at 1.5–2.5 mg/kg, sufentanil at 0.1 µg/kg and vecuronium at 0.1 mg/kg. Conversely, individuals in the OBA group were administered midazolam at 2 mg, dexamethasone at 0.1 mg/kg, propofol at 1.5–2.5 mg/kg, sufentanil at 0.4 µg/kg and vecuronium at 0.1 mg/kg during anaesthesia induction.
During the anaesthesia maintenance, patients in the MOSA group received dexmedetomidine at 0.2–0.5 µg/kg/hours until 30 min before the end of surgery, esketamine at 0.15 mg/kg/hours until 15 min before the end of surgery, lidocaine at 1.5 mg/kg/hours until the completion of the procedure, propofol at 4–12 mg/kg/hours and remifentanil at 0.05–0.15 µg/kg/min, with vecuronium used as required throughout the operation. Nalbuphine (10 mg) and parecoxib sodium (40 mg) were administered at the conclusion of pneumoperitoneum, while ondansetron (8 mg) and metoclopramide (10 mg) were given prior to abdominal closure. In contrast, patients in the OBA group were administered propofol at 4–12 mg/kg/hours, remifentanil at 0.1–0.5 µg/kg/min and vecuronium as needed during the operation. Similar to the MOSA group, nalbuphine (10 mg) and parecoxib sodium (40 mg) were given at the end of pneumoperitoneum, with ondansetron (8 mg) and metoclopramide (10 mg) administered before abdominal suturing. Further details are available in table 1.
Data collection, monitoring and management
Clinical data from the case report form will be manually entered into an electronic database, stored securely on a restricted-access server at Yan’an Hospital of Kunming City. Paper versions of materials will be securely stored in a locked strongbox at the hospital. Patient information will be anonymised for privacy protection. Once the trial is completed, the data will be securely archived and eventually deleted when no longer needed for research purposes.
Outcomes
Primary outcome
The primary outcome is the QoR-15 scores assessed on postoperative day 1. The QoR-15 instrument assesses recovery across five distinct dimensions: physical comfort, physical independence, emotional well-being, psychological support and pain. Each component is rated on an 11-point scale, with responses ranging from 0 representing ‘none of the time’ for positive aspects to 10 indicating ‘all of the time’, while the scoring is reversed for negative factors. The aggregate QoR-15 score spans from 0 denoting the poorest possible recovery outcome to 150 signifying the optimum recovery status.5 7 The QoR-15 will be conducted on the day before surgery and on POD 1. A QoR-15 score exceeding 90 was deemed indicative of a favourable recovery.13
Secondary outcomes
The secondary outcomes are as follows: the QoR-15 score on postoperative day 2; recovery of gastrointestinal function (time to first flatus, tolerance of liquid food or water and postoperative ileus-related morbidity); postoperative patient comfort and satisfaction; postoperative NRS values; incidence of PONV (will be defined as the presence of nausea, retching or vomiting14); the severity of PONV (will be measured using the simplified PONV impact scoring system developed Myles and Wengritzky, and a score of over 5 will be considered as clinically significant PONV15); intraoperative and postoperative opioid consumption by morphine equivalent consumption; the anxiety and depression levels of patients during the perioperation will be assessed using the Hospital Anxiety and Depression Scale (HADS), which consists of two subscales: anxiety and depression. Scores on the HADS range from 0 to 42, with higher scores indicating more severe symptoms16 17; and patients scoring 11 or higher may be classified as having potentially significant symptoms; intraoperative awareness of patients by modified Brice questionnaire18; length of hospital stays; blood gas analysis.
Assessment of safety
All procedures will be conducted in a fully equipped operating room with standardised haemodynamic monitoring to promptly identify and manage any adverse events. Any adverse events experienced by participants will be promptly reported to the principal investigator and treated. Suspected or unexpected serious adverse reactions will be reported to the national health agency. Detailed information on study-related adverse events will be documented in a case report form until resolution.
Statistical methods
Sample size
A change of six points or more on the QoR-15 difference indicates clinical improvement.13 19 According to our preliminary pilot study, the QoR-15 of LBS was 104.0±9.1 under the OBA protocol or 111.2±11.1 under the MOSA protocol. The PASS V.15.0.5 software for Windows (PASS, USA), a two-sided test was applied with a test efficacy of 0.05 and a power of 80% to calculate the required sample size, accounting for a 10% dropout rate. A total of 74 patients (37 in each group) are proposed for recruitment in this trial.
Planned descriptive statistics and outcome analysis
Continuous variables will be presented as mean (SD) or median (IQR). Categorical variables will be expressed as numbers and percentages. Statistical analyses will be conducted using SPSS software. The intention-to-treat principle will be applied. Data distribution will be examined using appropriate tests. Group comparisons will be made using independent samples t-test, repeated-measures analysis of variance, Mann-Whitney U test and χ2 test. The significance level will be set at 0.05.
Patient and public involvement
Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Ethics and dissemination
Ethical approval for this clinical trial was reviewed and provided by the Ethical Committee of Yan’an Hospital of Kunming City, Kunming, China (Chairperson Professor W Wang) on 15 December 2023 (approval No. 2023-240-01). Eligible patients will be enrolled after completion of clinical registration and subsequent to providing informed written consent to the investigator. The results of this study will be disseminated through peer-reviewed publications and/or presentations at conferences.
Discussion
This study conducted a single-centre, double-blind randomised controlled trial on assessing the impact of a novel analgesic protocol named MOSA, which combines esketamine, lidocaine, dexmedetomidine and a minimal opioid dose, on the postoperative recovery quality of patients undergoing LBS. The study will present scientific clinical evidence regarding the efficacy and safety of the MOSA protocol.
Opioids, traditional analgesics with a long history of use in pain management, have demonstrated significant efficacy in regulating autonomic nervous system responses to pain stimuli and in reducing the requirement for other anaesthetics in the perioperative period.20 21 Despite their effectiveness, opioids are associated with various adverse effects such as opioid-induced hyperalgesia, PONV, respiratory depression and ileus.22–27 Nevertheless, a complete elimination of opioids during the perioperative phase is deemed inappropriate.10
In light of the opioid crisis in the USA, there has been a growing interest in shifting towards alternative adjuvant medications for perioperative pain control.28 29 The concept of OFA or OSA has gained popularity among researchers and practitioners as a response to the opioid crisis, with evidence suggesting benefits in reducing postoperative pain, opioid-related complications and PONV.30–32
However, certain drawbacks of OFA have been noted, such as comparable postoperative pain scores to OBA and an increased incidence of bradycardia when dexmedetomidine is included in the OFA regimen.33 Patients who receive OFA with dexmedetomidine are confronted with delayed extubation, prolonged PACU stay, increased hypoxaemia and bradycardia after non-cardiac surgery.11
Considering the limitations of current approaches, the MOSA protocol is developed to investigate the impact on postoperative recovery in LBS patients by combining a minimal opioid dose with a low dose of dexmedetomidine, in alignment with the multimodal analgesia concept. Preliminary findings from a pilot study suggest that the MOSA protocol may mitigate opioid-related adverse effects and reduce complications associated with adjunctive medications like dexmedetomidine. This trial aims to provide valuable evidence and insights into perioperative pain management strategies for individuals undergoing LBS.
However, the study has several limitations including its single-centre nature, the potential for biased results in other settings and the need for further exploration of the MOSA protocol’s effects on a broader patient population. Despite these limitations, the trial is expected to contribute valuable information to the field of ERAS care for obese patients undergoing LBS procedures.
In summary, this prospective randomised controlled trial conducted in a single-centre setting will assess the impact of MOSA on postoperative recovery and perioperative complications among individuals undergoing LBS. The outcomes of this study, to be disseminated in a peer-reviewed journal, will contribute valuable insights to the field of ERAS for obese patients undergoing LBS interventions.
Trial status
The MOSA trial (V.1.0) commenced with 74 participants, and recruitment started on 19 December 2023 (the first one was recruited on 28 December 2023), with an anticipated completion date of 31 May 2025.
Ethics statements
Patient consent for publication
Acknowledgments
We would like to thank every patient participating in this trial, our colleagues in the Department of Anesthesiology, surgery consultants, nurses and caregivers for their help in facilitating this trial.
This post was originally published on https://bmjopen.bmj.com