Effects of an Opioid Free/Sparing Care Pathway for Patients Undergoing Obesity Surgery

Study Overview
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Brief Summary
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The opioid consumption has exploded in the western world, and for some patient populations such as obese patients, patients with sleep apnoea or patients undergoing cancer treatment, opioid-sparing/ opioid-free strategies could have positive effects on outcomes. Studies suggest that opioids could have opioid-induced immunosuppression, induce chronic post-operative pain syndrome and hyperalgesia in addition to the more well-known side effects such as respiratory depression, nausea, bladder, and bowel dysfunction. Hence, new studies are needed on the impact of person-centered care programs that combine pharmaceutical and non-pharmaceutical strategies to reduce the adverse short and long-term effects of opioid therapy. The overall aim is to evaluate the short-, medium- and long-term effects of opioid-free care pathways with or without person-centred care compared to conventional opioid-based treatment in patients undergoing obesity surgery. Specific aims Determine the effects of opioid-free care with or without person-centred care compared with conventional opioid-based general anaesthesia on the cognitive and physical quality of recovery after surgery up to 24 months after surgery (short-term: postoperative to discharge, medium-term: 14 days, 3 months, long-term: 6 months, 12 months and 24 months). Describe the clinical monitoring trend regarding nociceptive response intraoperatively between opioid-free and conventional care. Map the impact of opioid-free anaesthesia (with and without person-centred care) on the usage of opioids up to 24 months after hospital discharge. Explore the patients' experience of quality of life, self-efficacy and recovery after surgery in opioid-free care with or without person-centred care during the first year post-surgery. The aims will be evaluated by a prospective, randomized, non-blinded, non-commercial multi-centre study (Nov 2018-Dec 2022) approved by the Swedish Medicines Agency (EudraCT 2017003830-97) and the ethical review board (DNR 1006-17).

Detailed Description
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Aim To evaluate the effects of opioid sparing care pathways compared to conventional opioid-based treatment for pain relief, opioid consumption, recovery after surgery, self-efficacy and health economy in patients undergoing obesity surgery. The aim will be investigated by a prospective, randomized, non-blinded, non-commercial multi-centre study(Nov 2018-Dec 2022), approved by the Swedish Medicines Agency (EudraCT 2017003830-97) and the ethical review board (DNR 1006-17). Hypothesis 1. An opioid-free care pathway provides non-inferior pain relief as the conventional care with opioids during the post-operative phase. Primary endpoints: Determine the quality of recovery after surgery No difference in pain (NRS pain (0-10)) between opioid-free intervention with or without (Phase 1 & 2) person-centred care and conventional treatment (control group) during the postoperative phase until discharge to the surgical ward. An opioid-free intervention with or without (Phases 1 & 2) person-centred care improves recovery after surgery measured with the PostopQRS compared with conventional postoperative therapy, during hospitalisation and afterwards . Explorative endpoints Describe the intraoperative nociception level between opioid-free anaesthesia and conventional anaesthesia using the Medasense PMD-200 (NOL) monitor. Map the long-term prescription of opioids and analgesic drugs between the intervention group and the control group. Explore the patients' experiences with opioid-free intervention with or without person-centred care with conventional care regarding: self-efficacy measured with the General Self-Efficacy Scale (three months, six months, 12 months, 24 months). quality of life measured with the RAND-36 and EQ5D (three months, six months, 12 months, 24 months) patient experience and satisfaction, measured with the PostopQRS and interviews (two weeks, three months, 12 months) Power Pain: To determine noninferiority with a power of 0.8 (i.e., the probability of > 0.8 for the lower limit of a two-sided 95% confidence interval (using Fisher's nonparametric permutation test)), the difference of change in pain using the NRS from arrival to the recovery unit after surgery to discharge from the recovery unit will be used. Forty-three patients are required in each group and phase, with an SD for the change in the NRS estimated to be 1.62 from a small pilot study (noninferiority margin -1.0). The estimated change was assumed to be equal in the groups. To compensate for a potential interruption in the study or dropouts, we chose to include 55 patients in Intervention Phase 1, 55 patients in Intervention Phase 2 and a total of 110 patients in the control group (to follow intervention Phases 1 and 2, each 55 patients). Recovery after surgery: To detect an overall difference in the quality of recovery between groups over the entire study length, with a power of 0.8 and P < 0.05 and taking into consideration a dropout of over 30% as seen in other studies using the PQRS, we need to include at least 30 patients in each group 26. The control group will receive usual care and treatment according to the hospital's routines, where pain relief is obtained with opioids postoperatively. Pharmacological treatment in the intervention group differs solely from the patients in the usual group by replacing opioids with the following nonopioid perioperative treatment: dexmedetomidine, esketamine, lidocaine and TENS (for exact dosing, please visit ClinicalTrials.gov identifier: NCT03756961). Postoperative patient-controlled pain treatment with high-intensity/high-frequency TENS is used if the patient perceives pain over NRS ≧ 3 postoperatively and during remaining hospitalisation. Intervention Phase 1 tests the pharmacological and non-pharmacological interventions (TENS) compared to the control group that receives standard care with opioids intra- and postoperatively. Phase 2 intervention that follows after completion of Phase 1 intervention tests the pharmacological and nonpharmacological interventions compared to conventional treatment, supplemented by an evidenced-based PCC approach throughout the continuum of postoperative care. The two phases will primarily be analysed separately (i.e., between the control group and intervention Phase 1 and between the control group and intervention Phase 2).

Official Title
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Effects of an Opioid Sparing Care Pathway for Patients Undergoing Obesity Surgery

Conditions
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Obesity, Pain, Postoperative

Intervention / Treatment
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* Drug: Dexmedetomidine
* Behavioral: Person-centred care (PCC)
* Drug: Esketamine
* Drug: Lidocaine
* Device: Transcutaneous Nerve Stimulation (TENS)
* Drug: Remifentanil
* Drug: Desflurane
* Drug: Propofol
* Drug: Oxycodone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Patients ≥18 years planned to undergo laparoscopic obesity surgery (GBP alt Sleeve surgery) at the selected site. Exclusion Criteria: ASA> III Cardiovascular disease with bradycardia (<50 bpm) Serious liver disease failure Insufficient knowledge of the Swedish language Serious untreated psychiatric disease Neurocognitive dysfunction Pregnancy Women of childbearing age without contraception Malignant disease with expected short survival Patients treated with opioids for chronic pain Substance abuse Hypersensitivity to Oxycodone, Esketamine, Dexmedetomidine, and Lidocaine Pacemaker or ICD Inability to fill in questionnaires Decline participation,

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, randomized, non-blinded, non-commercial multi centre study. The intervention is divided into 2 phases, and the two phases will primarily be analysed separately (i.e., between the control group and intervention Phase 1 and between the control group and intervention Phase 2)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Control group: The patients receive the routine based anesthesiological treatment during bariatric surgery (Gastric By-Pass or Sleeve Gastrectomy). It consists of: General anesthesia induction: TCI Remifentanil Cpt 6 ng/ml/ Cp 3.2 ng/m, Propofol 1.5-2 mg/kg iv, Desflurane MAC (0.6-0.8). Maintained by Desflurane MAC (0.6-0.8) adjusted via BIS (40-60) and Remifentanil Cp 4-10 ng/ml. Post-operative pain management: Oxycodone 2.5 mg iv if the pain is rated by patient NRS ≧3. Paracetamol 1 g/6 h and Diclofenac 80 mg/24 h. | Drug: Remifentanil<br>* The control group receives general anesthesia with Remifentanil as the routine opioid drug during general anesthesia.<br>* Other names: Ultiva;Drug: Desflurane<br>* The patient receives general anesthesia with Desflurane as the routine volatile anesthetic during general anesthesia<br>* Other names: Desfluran;Drug: Propofol<br>* The patient receives general anesthesia with Propofol as the routine induction anaesthetic during general anesthesia<br>Drug: Oxycodone<br>* The control group receives Oxycodone as the routine pain management drug post-operative.<br>|
| Experimental: Intervention<br>Induction: Dexmedetomidine 0.2 micrograms/kg/h iv 5 min, Esketamine 0.1mg/kg + Propofol 1.5-2 mg/kg iv, Desflurane MAC (0.6-0.8). Maintained by Desflurane MAC (0.6-0.8) BIS (40-60), Dexmedetomidine 0.2 micrograms/kg/h, Esketamine 0.1-0.3mg/kg/h och 0.1 mg/kg in case of hypertension. At the end of surgery, Lidocaine 1 mg/kg iv (max 4 mg/kg /4 h) Post-operative: Dexmedetomidine (0.1-0.2 micrograms/kg/h up to 4 h post-operative). If the pain is rated NRS ≧3: Transcutaneous Nerve Stimulation (TENS) with high intensive 40-50 mA for 1 minute, if the patient still NRS ≧3, the TENS treatment is repeated one more time. If pain NRS ≧3 after two treatments with TENS: Esketamine 0.1mg/kg iv + Lidocaine 0.5 mg/kg iv (max 4 mg/kg /4 h) If pain NRS still ≧3 within 30 minutes after both TENS and Esketamine/Lidocaine, 2.5 mg Oxycodone iv, with a 10 minutes intervals until NRS < 3. Perioperative and at discharge, PCC will be used for the the intervention (Phase 2 patients) | Drug: Dexmedetomidine<br>* The intervention group will obtain the pharmacological treatment during both perioperative. Pharmacological treatment in the intervention group differs solely from the patients in the control group by replacing opioids with the following non-opioid treatment:<br>* Other names: Dexdor;Behavioral: Person-centred care (PCC)<br>* The intervention tests non-pharmacological interventions compared to conventional treatment, supplemented by an evidenced-based Person-centred care PCC approach throughout the continuum of the perioperative and until 4 weeks after discharge. This will be part of patients in Phase 2<br>* Other names: Phase 2;Drug: Esketamine<br>* The intervention group will obtain the pharmacological treatment perioperatively. Pharmacological treatment in the intervention group differs solely from the patients in the control group by replacing opioids with the following non-opioid treatment:<br>* Other names: Ketanest;Drug: Lidocaine<br>* The intervention group will obtain the pharmacological treatment perioperatively. Pharmacological treatment in the intervention group differs solely from the patients in the control group by replacing opioids with the following non-opioid treatment.<br>* Other names: Xylocaine;Device: Transcutaneous Nerve Stimulation (TENS)<br>* The intervention group will obtain non-pharmacological treatment by TENS during the entire hospital stay (both perioperative and post-operative) until discharge.<br>* Other names: TENS;Drug: Desflurane<br>* The patient receives general anesthesia with Desflurane as the routine volatile anesthetic during general anesthesia<br>* Other names: Desfluran;Drug: Propofol<br>* The patient receives general anesthesia with Propofol as the routine induction anaesthetic during general anesthesia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in post-operative pain from admission to the post-anesthesia care unit (PACO) to discharge from the PACO unit to the surgical ward. | Post-operative phase until discharge to the surgical ward. Pain assessed according to change in NRS (numeric rating scale). NRS (numeric rating scale for pain), (ranging from 0-10, no pain vs. worst imagined pain). | From date of randomization, difference in NRS will be assessed as the change in NRS from arrival (20 minutes after arrival) to the post-anesthesia care unit(PACU) after the surgery, to the time of discharge ( 4 hour) from the PACU to the surgical ward | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery after surgery | Investigating recovery after surgery measured with the The Post-operative Quality of Recovery Scale (PostopQRS) compared with conventional postoperative therapy. PostopQRS: Is a validated 5-dimensional instrument (Physiology, Nociception, Emotion, Cognition, ADL) in addition to questions about patient satisfaction. The scoring of recovery is 'return to baseline values or better' which requires a change score ≥ 0 for each question. The postoperative value for each test ( Cognition has a 2 scale tolerance due to day-to-day variation) is subtracted from the baseline value, and if no difference, then the patient is recovered. | (20 min, 40 min), during hospitalization (24 hours-72 hours) and afterwards (14 days, 30 days, three months, six months, 12 months and 24 months) | 
| Average opioid consumption perioperative | Investigating opioid consumption during the peri- and post-operative care period compared with conventional treatment until discharge from the hospital and up to 24 months discharge. | From the start of the Peri-operative phase (start of surgery) until discharge from hospital ( index stay), up to 24 months post-discharge | 
| Length of hospital stay | Length of indexed hospital stays calculated as the mean length in days from admission to discharge | Indexed length of hospital day will be calculated in days/hours). Estimated stay is 2 days | 
| Change in general Self-Efficacy | Investigating patient change in self-efficacy, measured with the General Self-Efficacy Scale (GSES). GSES is a validated questionnaire that contains 10 questions about the person's experiences of trust in his / her ability to handle difficult situations. The patient is asked to estimate his ability on a 4-point scale (1 not true) to 4 (true). The 10 answers are summed and a mean is calculated. Higher scores are better. | 3 months, six months, 12 months, 24 months. | 
| Change in Quality of Life | Investigating the quality of life measured with the RAND-36 RAND-36: The RAND-36 is a health-related quality of life (HRQoL) It is comprised of 36 items assessing eight areas: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, emotional well-being, energy/fatigue, pain, and general health perceptions. Each item is scored 0-100, and are than summarized. 0 is low, 100 is the highest score to get. | (3 months, six months, 12 months, 24 months) | 
| Exploring patient experience | Investigating patient experience and satisfaction during the hospital stay, measured with the PPE-15, a 15 item questionnaire. The PPE15 is a validated short version of The Picker Care experience survey (40 item). Each item has response alternatives ranging from no problem, some problem, problem. Each response is coded either as a problem ( problem, some problem) or as no problem. Problem is scored as=1, no problem=0. The mean is calculated both on item level and as a total score. | 2 weeks after hospital discharge | 
| Change in health status | Investigating the change in health status measured with the EuroQol 5 dimension (EQ5D). EQ-5D is a standardized instrument for measuring generic health status, covering five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 responses: no problems, some problems, and extreme problems. This response results into a number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. | (3 months, six months, 12 months, 24 months) | 
| Unplanned re-admission | Investigating re-admission (un-planned) between groups. | From time of surgery up until 24 months post-surgery | 
| Mortality | Investigating mortality rate between groups. | From time of surgery up until 24 months post-surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioids, bariatric surgery, anesthesia, opioid-free, person-centred care, recovery, TENS, pain