Spinal anesthesia as an adjunct to general anesthesia for robotic assisted laparoscopic prostatectomy – a randomised placebo-controlled trial

Spinal anesthesia as an adjunct to general anesthesia for robotic assisted laparoscopic prostatectomy – a randomised placebo-controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Spinal anesthesia as an adjunct to general anesthesia for robotic assisted laparoscopic prostatectomy – a randomised placebo-controlled trial Marisa Antunes, Ada Holtan, Daniel Johansen, Erling Aarsæther, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8689169/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Novel surgical techniques have facilitated faster recoveries after radical laparoscopic prostatectomy, yet abdominal pain and urinary catheter related discomfort remain a clinical challenge. We hypothesised that spinal anesthesia as an adjunct to general anesthesia would facilitate faster recovery and less postoperative pain and discomfort compared to standard medical treatment. Methods A double-blind randomised study was designed with one group (n = 15) allocated to general anesthesia and intrathecal injection of hyperbaric bupivacaine (7.5 mg)/spinal morphine (100 µg), while controls (n = 15) received general anesthesia and a sham spinal procedure before they underwent robotic prostatectomy. Two hours before induction of anesthesia, all patients received orally paracetamol 1 g, dexamethasone 8 mg and etoricoxib 90 mg. General anesthesia was performed using remifentanil, propofol and rocuronium. Postoperative analgesia consisted of intravenous morphine via a patient-controlled device, oral etoricoxib 90 mg x 1 and paracetamol 1 gr x 4. Primary outcome measure was time to discharge from the post anesthesia care unit (PACU). Secondary outcome measures were postoperative pain and opioid consumption. Results Patients who received spinal anesthesia were discharged earlier from the PACU (p = 0.010) and reported less pain on admittance to the PACU and after 2 hrs (p = 0.019 and p < 0.001, respectively). Furthermore, peak pain score (p = 0.007) and opioid consumption (p = 0.04) were lower in the spinal group during the PACU stay. Patients who received spinal anesthesia reported less discomfort related to bladder spasm (p = 0.021) and urgency (p < 0.001). Quality of recovery-15 score was higher in the spinal group (p < 0.001). No attributable side effects related to spinal anesthesia and intrathecal morphine were observed. Conclusions Spinal anesthesia as an adjunct to general anesthesia facilitated faster recovery, better pain relief and less discomfort compared to standard medical treatment after robotic assisted laparoscopic prostatectomy. Patients in the spinal group were more satisfied as assessed by QoR-15. Prostatectomy Cancer Pain Spinal anesthesia Enhanced recovery Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The steady increase in life expectancy among men has led to a sharp increase in both incidence and prevalence of prostate cancer( 1 ). Radical prostatectomy remains the mainstay of surgical treatment representing a curative option for those with localized disease and a survival benefit for those with advanced disease( 2 ).With technologic advances, the traditional open retropubic radical prostatectomy has been replaced by minimally invasive techniques and robotic assisted prostatectomy has become the standard of care( 3 ). Evolution of novel surgical techniques have facilitated faster recoveries, yet postoperative pain remains a clinical challenge, for which multimodal analgesia is recommended( 4 ). However, abdominal pain and urinary catheter related discomfort remain as a clinical challenge and main barrier for same-day discharge from hospital( 5 ). Spinal anesthesia is not recommended as an adjunct to general anaesthesia for laparoscopic radical prostatectomy by the Enhanced Recovery After Surgery (ERAS) programme( 4 ). This could be due to a low number of clinical trials as well as concerns related to administration of intrathecal morphine. However, concerns related to side effects and complications caused by intrathecally administrated morphine is largely rooted in older studies and associated with the use of higher doses of morphine ( 6 – 8 ). The prolonged analgesic effect of intrathecal morphine may be particularly advantageous in the treatment of postoperative pain and discomfort after prostatectomy. We hypothesised that spinal anesthesia as an adjunct to general anesthesia would facilitate faster recovery and less pain and discomfort in patients undergoing robotic assisted prostatectomy. A pilot study was performed for power and sample size estimations. Patients in the intervention group received spinal anesthesia consisting of 100 µg spinal morphine and 7.5 mg hyperbaric bupivacaine, while patients in the placebo group received a sham spinal procedure. Data analyses revealed large differences between the groups for pain scores, need for rescue analgesics, and time ready for discharge. We considered time ready for discharge from the post anesthesia care unit (PACU) as a clinically relevant and valid parameter for power and sample size estimation. Pilot data revealed a need for 15 patients in each group in order to show a difference with a power of 0.84 at the 0.05 significance level. A double-blind placebo-controlled study was subsequently designed. Aim for study was to test the hypothesis that spinal anesthesia as an adjunct to general anesthesia would facilitate faster recovery and less postoperative pain and discomfort compared to standard medical treatment. Methods Power and sample size estimation A pilot study was performed for power and sample size estimations. Time required to meet the PACU discharge criteria was applied for the power and sample size estimation. Group sample sizes of 15 and 15 achieved 84% power to detect a difference of 211,0 minutes between the null hypothesis mean difference of 0,0 and the actual mean difference of -211,0 at the 0,050-significance level (alpha) using a two-sided Mann-Whitney Test. These results are based on 2000 Monte Carlo samples from the nill distributions: Normal (M0 S) and Normal (M0 S), and the alternative distributions: Normal (M0 S) and Normal (M1 A). Screening and data collection The research protocol was approved by the regional committee for medical and health research ethics in Norway (REC 866656) and by the Institutional Regulatory Board (Record ID 2025/3168-6). The study was registered at https://clinicaltrials.gov (NCT06860893) and complies with the Declaration of Helsinki. Patients scheduled for robotic prostatectomy at the University Hospital of North Norway were screened for inclusion. Inclusion criteria were prostate cancer patients eligible for robotic prostatectomy and age 18–80 years. Exclusion criteria were American Society of Anaesthesiologists Classification (ASA) IV, contraindications to spinal anaesthesia, allergy to any of the drugs used in this study protocol, chronic use of opioids or steroids, liver or renal impairment (GFR < 60 ml/min), obstructive sleep apnea, cognitive impairment, and patients scheduled for synchronous laparoscopic surgery of other organs. Written informed consent was obtained from all participants. In the preoperative clinic the attending anaesthesiologist (MA) informed the patients about the numeric rating scale (NRS) and how to manage the patient-controlled analgesia (PCA) device. Patients were randomized by an independent colleague (LMY). Randomisation was performed by using sealed, opaque envelopes stored at a secure location in the holding area. Only the anesthetic team was thus aware of the actual treatment arm. Accordingly, patients, surgical team, PACU nurses, and nurses on the ward were all blinded. Patient assessment and data registration were performed by independent assessors (AGH and DJ) who were blinded for the actual treatment arm. Patients who had a risk of lymph node metastases above 7% according to the 2018 Briganti nomogram were subjected to extended pelvic lymph node dissection in addition to prostatectomy in accordance with European Guidelines for treatment of prostate cancer( 2 ) Anesthesia procedure Two hours before induction of anesthesia, all patients received orally trimethoprim/sufamethoxazole 160 mg, 200 mL of a carbohydrate-loaded drink (ProvideXtra®, Fresenius Kabi, Norway), paracetamol 1 g, dexamethasone 8 mg and etoricoxib 90 mg. Anesthesia was performed with propofol and remifentanil using a target-controlled infusion protocol (TCI). Muscle relaxation was induced with intravenous rocuronium 0.6–1.2 mg/kg (ideal weight). Anesthesia depth was monitored by bispectral index (BIS) monitors and adjusted according to clinical judgement. Vasoactive medication (ie, phenylephrine, ephedrine, and norepinephrine) was given to maintain mean arterial pressure (MAP) ≥ 65 mm Hg and Ringer’s acetate was infused to target zero fluid balance during the operation. Thermal blanket was used to preserve body temperature. Ondansetron 4 mg and butylscopolamin 20 mg were given intravenously 30 min before emergence from anesthesia. By end of surgery the trocar insertion sites were infiltrated with a total of 20 mL bupivacaine 2.5 mg/mL containing adrenalin 5 µg/mL. Train of four (TOF) was applied to guide reversal of muscle blockade by using appropriate dosages of sugammadex. Before emergence from anesthesia 100 µg fentanyl was given intravenously to patients allocated to the sham spinal procedure Treatment Arms Patients were allocated to either intrathecal injection of bupivacaine/morphine or a sham spinal procedure (Fig. 1 ). Patients in both groups were sitting and the skin over the lumbar region of the back was disinfected with chlorhexidine and draped sterile. In the intervention group the skin was infiltrated with 5 mL of lidocaine 10 mg/mL and a 27-gauge pencil-point needle (Pajunk, GA, USA) was subsequently entered into the intrathecal space at the L2–3 or L3–4 interspace. After obtaining return of cerebrospinal fluid, hyperbaric bupivacaine 5 mg/mL 1,5 mL (7,5 mg) and spinal morphine 200 µg/mL, 0.5 mL (100 µg) was injected. Patients in the placebo group received a skin infiltration with 5 mL of lidocaine 10 mg/mL while the attending anesthesiologist pressed one finger at the skin and talked as if she was giving an intrathecal injection at the L3–4 interspace. Sedation with propofol and remifentanil was initiated and maintained during the administration of subcutaneous local anesthesia and/or spinal anesthesia, with the intent to prevent the patient´s awareness of the actual treatment arm. Surgical Procedure After induction of anesthesia, the abdomen and genitals were disinfected and surrounded with sterile surgical drapes. An indwelling 18 Ch urine catheter (Bard Biocath®, BD Oslo, Norway) was inserted, and the patients were tilted in the 30-degree head-down position. All procedures were performed with the da Vinci XI® or da Vinci X systems (Intuitive Surgical Inc., Sunnyvale, CA, USA), using a standardized 4-arm transperitoneal 6-port approach with a 0° lens, a maryland bipolar forceps, monopolar curved scissors and a ProGrasp™ forceps (Intuitive Surgical Inc., Sunnyvale, CA, USA) as previ( 9 ). The bladder was dissected downwards by entering the space of Retzius ( 3 ). The bladder neck was meticulously released from the base of the prostate, before it was cut. After the division of the bladder neck was completed dorsally, the vasa deferentia were identified in the midline where they were cut, and the seminal vesicles were dissected free. Nerve-sparing was routinely performed on one or both sides, depending on whether the distance from to the tumor to the neurovascular bundle was considered adequate to avoid positive surgical margins. The length of the urethra was preserved similarly. After the anastomosis between the bladder neck and urethra was successfully completed, the specimen was extracted by a vertical, midline incision above the umbilicus. Trocar incisions were infiltrated with a total of 20 ml bupivacaine 2.5 mg/ml with adrenalin 5 µg/ml. The fascia of the midline incision and in the right lateral 12 mm port incision were sutured with a polydiaxon suture. The skin was closed with staples. Postoperative recordings and pain management in the PACU Patients in both groups received oral paracetamol 1 gr every 6 hours. Morphine 2.5–5 mg was administered intravenously by the PACU nurse if NRS was > 3. PCA was initiated as soon as the patients scored NRS < 4. PCA consisted of 3 mg morphine with 15 minutes lockout time. The Bromage score was applied to test for motor blockade on admittance and after 2 hrs in the PACU. Postoperative pain management in the ward Patients in both groups receive postoperatively oral paracetamol 1 gr every 6 hours. A second dose etoricoxib 90 mg was given at 07:00 on postoperative day 1. PCA morphine was continued in the ward. Statistics Primary outcome measure was time to discharge from PACU. Secondary outcome measures were postoperative pain and opioid consumption. Repeated measures analysis of variance was applied to test for differences in NRS. The Mann–Whitney U-test was used to test for time specific data analyses. The Fisher’s exact test was applied for ordinal data. P ≤ 0.05 was deemed statistically significant. SPSS version 29.0 (IBM, Armonk, NY, USA) was used for all calculations and for production of graphic material. Results Patients were consecutively recruited in accordance with the inclusion and exclusion criteria (Fig. 2 ). Four patients declined to participate because they were worried about potential complications related to spinal anesthesia. Included patients were treated in accordance with the study protocol, and all data were included in the final analyses. Age, body mass index (BMI), and American Society of Anesthesiologists physical status classification system (ASA) were not significantly different between the two groups (Table 1 ). Surgery time was equal in both groups. Patients in the spinal group needed less remifentanil compared to the placebo group (Table 2 , p = 0.01), while intraoperative dose of propofol and noradrenaline did not differ between the study groups (p = 0.31 and p = 0.68, respectively). Table 1 Patient demographics. Median (range) Spinal (n = 15) Placebo (n = 15) P * Age 68 (62–74) 63 (50–73) 0.12 BMI 27 (23–34) 29 (23–35) 0.37 ASA I/II/III 0/15/0 0/15/0 1.0 ASA; American Society of Anesthesiologists physical status classification system. BMI; Body mass index. Note: *Mann-Whitney U-test Table 2 Intraoperative data. Median (range) Spinal (n = 15) Placebo (n = 15) p * RALP with epld 9 6 0.6 RALP without epld 6 9 0.6 Time of surgery (minutes) 146 (74–185) 146 (77–232) 0.46 Total dose of propofol (mg) 1664 (763–2425) 1790 (1000–3077) 0.31 Total dose of remifentanil (µg) 1463 (854–3240) 2625 (1300–4954) 0.01 Total dose noradrenaline (ng) 310 (120–1300) 230 (60–790) 0.68 Note: *Mann-Whitney U-test Table 3 Pain, discomfort and quality assessment. Median (range) Spinal (n = 15) Placebo (n = 15) P * Peak pain score 4 ( 1 – 9 ) 6( 3 – 9 ) 0.007 Bladder spasm 0 (0–2) 2 (0–4) 0.02 Urgency 0 (0–2) 2 (0–4) < 0.001 Opioid consumption 0 (0–14) 5 (0–28) 0.04 QoR 139 (108–150) 114 (67–132) < 0.001 QoR-15; Quality of recovery 15. Patients who received spinal anesthesia were discharged earlier from the PACU (Fig. 3 , p = 0.01). Repeated analyses of variance revealed that NRS decreased in both groups over time. However, analysis of between group effect showed that NRS at rest was significantly lower in the spinal group (Fig. 4 , p < 0.001). A similar pattern was observed for NRS after a forced cough where pain decreased over time, while analysis of between group effect revealed lower NRS in the spinal group (Fig. 5 , p < 0.001). Furthermore, peak pain score and opioid consumption during the stay in the PACU were lower in the spinal group, p = 0.007 and p = 0.04, respectively. Patients who received spinal anesthesia reported less bladder spasm (p = 0.02) and less urgency (p < 0.001). Quality of recovery-15 score was higher in the spinal group (p < 0.001). The Bromage score was recorded without any signs of motor blockade during the stay in PACU. No other attributable side effects related to spinal anesthesia and/or intrathecal morphine were recorded. All patients were discharge from hospiat on postoperative day 1, except from 1 patient in each group who were discharge on day two due to poor logistics. Discussion Data from the current study revealed significant benefits from spinal anesthesia as an adjunct to general anesthesia in patients undergoing robotic assisted laparoscopic prostatectomy. Improved pain relief and less discomfort facilitated faster recovery, and more satisfied patients in the spinal group compared to patients in the placebo group. A multimodal approach for pain management is fundamental in all ERAS protocols and effective analgesia without delayed recovery is the primary goal. ERAS involves a series of evidence-based procedures for optimizing perioperative treatment with the aim of reducing the physical and psychological stresses of surgical trauma and thus accelerating patients’ recovery( 10 ). Lin et al tested this concept in prostate cancer patients who were undergoing laparoscopic radical prostatectomy( 11 ). They found that implementation of an ERAS protocol effectively accelerated patient rehabilitation and reduced length of stay (LOS) and hospitalization costs. The ERAS concept has been implemented in our hospital for many years, introduced and lead by Professor Arthur Revhaug who was a co-founding member of the ERAS Study Group and later the ERAS® Society( 12 ). In the current study all patients received treatment in accordance with ERAS recommendations including preoperative counselling, carbohydrate fluid loading, targeted intraoperative fluid resuscitation and temperature control, no drains, multimodal analgesics, early mobilization, and early postoperative drinking and eating. Despite all these measures, patients in the placebo group suffered from significant postoperative pain and discomfort. Median and range of NRS on activity after 2 hours in PACU was 5 ( 3 – 9 ) compared to the spinal group 2(0–4). Furthermore, spinal anesthesia was very effective to alleviate discomfort related to bladder spasm and urgency. Patients in the spinal group received less remifentanil during anesthesia, which is likely due to the analgetic effects of intrathecal morphine and bupivacaine. Furthermore, there was less need for rescue pain medication in the spinal group. These findings are very much in line with a previous study where we showed the potential benefit of spinal anesthesia as an adjunct to general anaesthesia after laparoscopic abdominoperineal rectal amputation( 13 ). Administration of intrathecal morphine at a lower dose (100 µg) has consistently been reported to be safe practice without causing respiratory complications( 14 – 16 ). Concerns related to the use of intrathecal morphine are most likely rooted in older studies in which higher doses of morphine were administrated, and often in clinical settings with limited access to adequate monitoring. The aim of using 100 µg of intrathecal morphine in the current study was to provide effective analgesia, while ensuring patient safety without the need to intensify clinical monitoring. Two interesting studies are relevant to discuss in this context. Koning et al combined 300 µg intrathecal morphine with 12.5 mg bupivacaine( 6 ), while Shim et al combined 200 µg intrathecal morphine with 7.5 mg bupivacaine( 17 ). Both studies demonstrated lower postoperative pain scores and reduced in-hospital cumulative morphine consumption, and neither reported any major respiratory or cardiovascular complications. The only principal adverse effect observed was a modestly increased incidence of pruritus in the 300µg group( 6 ). Furthermore, Shim et al did not assess bladder spasm or urgency symptoms and quality of patient recovery was not reported. Anyway, data from both studies demonstrated the analgetic potency of intrathecal morphine in patients undergoing laparoscopic prostate surgery. Despite current evidence, neither the ERAS® Society nor PROSPECT recommend spinal analgesia as an adjunct to general anesthesia for robotic assisted laparoscopic prostatectomy. We believe it is time to review and update these recommendations, yet knowledge gaps related to dose–response parameters and potential ceiling effect of neuraxial morphine remain and should be studied in future clinical trials. PROSPECT arguments against the use of intrathecal morphine as first-line analgesia in minimally invasive prostatectomy refers to the risk of serious potential side effects, limited evidence for low-dose regimens, and unclear analgesic duration( 4 ). Co-administration of other drugs may have also contributed to some earlier reports of adverse events after a single shot spinal. Our decision to combine 100 µg of intrathecal morphine with 7.5 mg of hyperbaric bupivacaine was guided by evidence from studies in cesarean delivery and minimally invasive colorectal surgery, where low-dose intrathecal opioids provide effective analgesia without side effects( 13 ). The rationale for employing a low dose of bupivacaine was to potentiate the analgesic effect of morphine, particularly in the intraoperative period, while minimizing the risk of residual motor block during the immediate postoperative recovery period. In recent years, there has been an increasing interest in the use of abdominal wall blocks for pain relief after caesarean delivery and laparoscopic surgery( 18 ). However, the quality of analgesia provided by intrathecal morphine has consistently proven superior, reinforcing its role as a valuable component of multimodal analgesic strategies that combine efficacy, safety, and practicality in routine clinical practice. Although spinal anesthesia is well established in clinical practice, several issues remain to be studied. Different drug combinations and dosing open the possibility of a true “multimodal spinal anesthesia”, further enhancing its potential and versatility. Mastering spinal anesthesia is invaluable in the setting of a busy contemporary hospital, but it also remains feasible and highly relevant in low-resource environments. The evolution of anesthetic practice should therefore consider not only technological advances but also the preservation and refinement of simple, effective, and universally applicable techniques such as spinal anesthesia, which is not time-consuming, easy to learn, and largely independent of other technologies. Limitations to this study include the single-center design and the relatively small sample size. We did not perform a dose-finding trial, so ED₅₀ and ED₉₀ for intrathecal morphine in this population remains to be studied. Follow-up was limited to the immediate postoperative period, and longer-term outcomes were not assessed. Despite these limitations, we believe the current study adds valuable data in support of using low-dose spinal morphine for postoperative pain relief after robotic assisted laparoscopic prostatectomy. Conclusions Optimizing perioperative analgesia is a priority in modern anesthesiology, balancing effective pain relief against potential adverse side effects. In the current study, spinal anesthesia as an adjunct to general anesthesia enhanced recovery after surgery and improved patient-reported outcomes following robotic assisted radical prostatectomy. Although PROSPECT guidelines currently advise against spinal morphine, our findings support its feasibility, safety, and potential clinical benefit. Low-dose spinal morphine merits consideration as part of multimodal analgesic strategies for prostatectomy, yet further prospective studies are warranted in order to define optimal dosing and establish its role in contemporary perioperative pain management. Abbreviations ERAS; Enhanced Recovery After Surgery NRS; Numeric Rating Scale PACU; Post Anesthesia Care Unit PROSPECT; Procedure Specific Postoperative Pain Management QoR-15; Quality of Recovery-15 Declarations The research protocol was approved by the regional committee for medical and health research ethics in Norway (REC 866656) and by the Institutional Regulatory Board (Record ID 2025/3168-6). The study was registered at https://clinicaltrials.gov (NCT06860893) on February 28 th , 2025, before inclusion of the first patient. Unfortunately, the primary outcome parameter was wrongly stated in the original submission to Clinical Trials Gov. This mistake was later corrected and documented in the Clintrials.gov file history. We apologize for this mistake. Ethics approval and consent to participate: The research protocol was approved by the regional committee for medical and health research ethics in Norway (REC 866656), UiT- The Arctic University of Norway, Postbox 6050 Langnes, 9037 Tromsø, Norway and by the Institutional Regulatory Board (Record ID 2025/3168-6), University Hospital of North Norway, 9038 Tromsø, Norway. Written informed consent was obtained from all participants. Funding: Open access funding was provided by UiT The Arctic University of Norway. Author Contribution M.A and L.M.Y. had the original idea. M.A, A.G.H., and D.J. performed the study. The manuscript was drafted by all authors. All authors contributed to, read and approved the final manuscript. Acknowledgement We thank all patients who participated. We also thank the nurses and doctors who were involved in the treatment and care of the patients. Data Availability All data and material will be made available on reasonable request to the corresponding author. 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Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 25 Feb, 2026 Editor assigned by journal 23 Feb, 2026 Editor invited by journal 05 Feb, 2026 Submission checks completed at journal 03 Feb, 2026 First submitted to journal 03 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Antunes","email":"data:image/png;base64,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","orcid":"","institution":"University Hospital of North Norway","correspondingAuthor":true,"prefix":"","firstName":"Marisa","middleName":"","lastName":"Antunes","suffix":""},{"id":596896451,"identity":"4262e1fe-e408-4e9a-92f4-de68b2690db2","order_by":1,"name":"Ada Holtan","email":"","orcid":"","institution":"UiT The Arctic University of Norway","correspondingAuthor":false,"prefix":"","firstName":"Ada","middleName":"","lastName":"Holtan","suffix":""},{"id":596896452,"identity":"d96dc3d1-f5ac-41e3-81f8-1d112249c653","order_by":2,"name":"Daniel Johansen","email":"","orcid":"","institution":"UiT The Arctic University of Norway","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Johansen","suffix":""},{"id":596896453,"identity":"a3b56bac-b015-4d1a-83f7-34df494e9f70","order_by":3,"name":"Erling Aarsæther","email":"","orcid":"","institution":"University Hospital of North Norway","correspondingAuthor":false,"prefix":"","firstName":"Erling","middleName":"","lastName":"Aarsæther","suffix":""},{"id":596896454,"identity":"7edf934a-28b2-4162-81bb-7902dee3947c","order_by":4,"name":"Lars Marius Ytrebo","email":"","orcid":"","institution":"UiT The Arctic University of Norway","correspondingAuthor":false,"prefix":"","firstName":"Lars","middleName":"Marius","lastName":"Ytrebo","suffix":""}],"badges":[],"createdAt":"2026-01-24 21:38:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8689169/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8689169/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103613927,"identity":"8c4c3716-1215-48b2-b91e-dbd596cc921c","added_by":"auto","created_at":"2026-02-27 16:23:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":376718,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment allocation\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8689169/v1/fb14e5db9792ca6e71371be6.png"},{"id":103613924,"identity":"28b3b1a2-785a-4681-a040-68b8ba06d811","added_by":"auto","created_at":"2026-02-27 16:23:40","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":110602,"visible":true,"origin":"","legend":"\u003cp\u003eConsort flow diagram\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8689169/v1/6c73e3635adfd5367bf76371.jpg"},{"id":103613895,"identity":"995bdd55-95a6-4a7b-8fbe-fae4701599be","added_by":"auto","created_at":"2026-02-27 16:23:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":15016,"visible":true,"origin":"","legend":"\u003cp\u003eTime to ready for discharge from PACU\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8689169/v1/a72462d8441e7db3962d1bcf.png"},{"id":103613926,"identity":"d18a2011-12f8-4947-b360-2a04dd3b08ed","added_by":"auto","created_at":"2026-02-27 16:23:41","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":17870,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8689169/v1/a6007f78687d9303603a6311.png"},{"id":103614065,"identity":"407443df-792d-4154-b523-5ac1dadf6c40","added_by":"auto","created_at":"2026-02-27 16:24:17","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":19097,"visible":true,"origin":"","legend":"\u003cp\u003eNRS after a forced cough in PACU and in the ward\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8689169/v1/c36d88ffd97187960c8b0b60.png"},{"id":103614494,"identity":"0dac3b1a-761a-4258-8ef6-5504d53503bd","added_by":"auto","created_at":"2026-02-27 16:25:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1059121,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8689169/v1/b974f3f5-353f-45de-8adb-1ddd0b0c3322.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Spinal anesthesia as an adjunct to general anesthesia for robotic assisted laparoscopic prostatectomy – a randomised placebo-controlled trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe steady increase in life expectancy among men has led to a sharp increase in both incidence and prevalence of prostate cancer(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Radical prostatectomy remains the mainstay of surgical treatment representing a curative option for those with localized disease and a survival benefit for those with advanced disease(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).With technologic advances, the traditional open retropubic radical prostatectomy has been replaced by minimally invasive techniques and robotic assisted prostatectomy has become the standard of care(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Evolution of novel surgical techniques have facilitated faster recoveries, yet postoperative pain remains a clinical challenge, for which multimodal analgesia is recommended(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). However, abdominal pain and urinary catheter related discomfort remain as a clinical challenge and main barrier for same-day discharge from hospital(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSpinal anesthesia is not recommended as an adjunct to general anaesthesia for laparoscopic radical prostatectomy by the Enhanced Recovery After Surgery (ERAS) programme(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). This could be due to a low number of clinical trials as well as concerns related to administration of intrathecal morphine. However, concerns related to side effects and complications caused by intrathecally administrated morphine is largely rooted in older studies and associated with the use of higher doses of morphine (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The prolonged analgesic effect of intrathecal morphine may be particularly advantageous in the treatment of postoperative pain and discomfort after prostatectomy. We hypothesised that spinal anesthesia as an adjunct to general anesthesia would facilitate faster recovery and less pain and discomfort in patients undergoing robotic assisted prostatectomy. A pilot study was performed for power and sample size estimations. Patients in the intervention group received spinal anesthesia consisting of 100 \u0026micro;g spinal morphine and 7.5 mg hyperbaric bupivacaine, while patients in the placebo group received a sham spinal procedure. Data analyses revealed large differences between the groups for pain scores, need for rescue analgesics, and time ready for discharge. We considered time ready for discharge from the post anesthesia care unit (PACU) as a clinically relevant and valid parameter for power and sample size estimation. Pilot data revealed a need for 15 patients in each group in order to show a difference with a power of 0.84 at the 0.05 significance level. A double-blind placebo-controlled study was subsequently designed. Aim for study was to test the hypothesis that spinal anesthesia as an adjunct to general anesthesia would facilitate faster recovery and less postoperative pain and discomfort compared to standard medical treatment.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePower and sample size estimation\u003c/h2\u003e \u003cp\u003eA pilot study was performed for power and sample size estimations. Time required to meet the PACU discharge criteria was applied for the power and sample size estimation. Group sample sizes of 15 and 15 achieved 84% power to detect a difference of 211,0 minutes between the null hypothesis mean difference of 0,0 and the actual mean difference of -211,0 at the 0,050-significance level (alpha) using a two-sided Mann-Whitney Test. These results are based on 2000 Monte Carlo samples from the nill distributions: Normal (M0 S) and Normal (M0 S), and the alternative distributions: Normal (M0 S) and Normal (M1 A).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eScreening and data collection\u003c/h3\u003e\n\u003cp\u003eThe research protocol was approved by the regional committee for medical and health research ethics in Norway (REC 866656) and by the Institutional Regulatory Board (Record ID 2025/3168-6). The study was registered at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://clinicaltrials.gov\u003c/span\u003e\u003cspan address=\"https://clinicaltrials.gov\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (NCT06860893) and complies with the Declaration of Helsinki.\u003c/p\u003e \u003cp\u003ePatients scheduled for robotic prostatectomy at the University Hospital of North Norway were screened for inclusion. Inclusion criteria were prostate cancer patients eligible for robotic prostatectomy and age 18\u0026ndash;80 years. Exclusion criteria were American Society of Anaesthesiologists Classification (ASA) IV, contraindications to spinal anaesthesia, allergy to any of the drugs used in this study protocol, chronic use of opioids or steroids, liver or renal impairment (GFR\u0026thinsp;\u0026lt;\u0026thinsp;60 ml/min), obstructive sleep apnea, cognitive impairment, and patients scheduled for synchronous laparoscopic surgery of other organs. Written informed consent was obtained from all participants. In the preoperative clinic the attending anaesthesiologist (MA) informed the patients about the numeric rating scale (NRS) and how to manage the patient-controlled analgesia (PCA) device. Patients were randomized by an independent colleague (LMY). Randomisation was performed by using sealed, opaque envelopes stored at a secure location in the holding area. Only the anesthetic team was thus aware of the actual treatment arm. Accordingly, patients, surgical team, PACU nurses, and nurses on the ward were all blinded. Patient assessment and data registration were performed by independent assessors (AGH and DJ) who were blinded for the actual treatment arm. Patients who had a risk of lymph node metastases above 7% according to the 2018 Briganti nomogram were subjected to extended pelvic lymph node dissection in addition to prostatectomy in accordance with European Guidelines for treatment of prostate cancer(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003ch3\u003eAnesthesia procedure\u003c/h3\u003e\n\u003cp\u003eTwo hours before induction of anesthesia, all patients received orally trimethoprim/sufamethoxazole 160 mg, 200 mL of a carbohydrate-loaded drink (ProvideXtra\u0026reg;, Fresenius Kabi, Norway), paracetamol 1 g, dexamethasone 8 mg and etoricoxib 90 mg.\u003c/p\u003e \u003cp\u003eAnesthesia was performed with propofol and remifentanil using a target-controlled infusion protocol (TCI). Muscle relaxation was induced with intravenous rocuronium 0.6\u0026ndash;1.2 mg/kg (ideal weight). Anesthesia depth was monitored by bispectral index (BIS) monitors and adjusted according to clinical judgement. Vasoactive medication (ie, phenylephrine, ephedrine, and norepinephrine) was given to maintain mean arterial pressure (MAP)\u0026thinsp;\u0026ge;\u0026thinsp;65 mm Hg and Ringer\u0026rsquo;s acetate was infused to target zero fluid balance during the operation. Thermal blanket was used to preserve body temperature. Ondansetron 4 mg and butylscopolamin 20 mg were given intravenously 30 min before emergence from anesthesia. By end of surgery the trocar insertion sites were infiltrated with a total of 20 mL bupivacaine 2.5 mg/mL containing adrenalin 5 \u0026micro;g/mL. Train of four (TOF) was applied to guide reversal of muscle blockade by using appropriate dosages of sugammadex. Before emergence from anesthesia 100 \u0026micro;g fentanyl was given intravenously to patients allocated to the sham spinal procedure\u003c/p\u003e\n\u003ch3\u003eTreatment Arms\u003c/h3\u003e\n\u003cp\u003ePatients were allocated to either intrathecal injection of bupivacaine/morphine or a sham spinal procedure (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Patients in both groups were sitting and the skin over the lumbar region of the back was disinfected with chlorhexidine and draped sterile. In the intervention group the skin was infiltrated with 5 mL of lidocaine 10 mg/mL and a 27-gauge pencil-point needle (Pajunk, GA, USA) was subsequently entered into the intrathecal space at the L2\u0026ndash;3 or L3\u0026ndash;4 interspace. After obtaining return of cerebrospinal fluid, hyperbaric bupivacaine 5 mg/mL 1,5 mL (7,5 mg) and spinal morphine 200 \u0026micro;g/mL, 0.5 mL (100 \u0026micro;g) was injected. Patients in the placebo group received a skin infiltration with 5 mL of lidocaine 10 mg/mL while the attending anesthesiologist pressed one finger at the skin and talked as if she was giving an intrathecal injection at the L3\u0026ndash;4 interspace. Sedation with propofol and remifentanil was initiated and maintained during the administration of subcutaneous local anesthesia and/or spinal anesthesia, with the intent to prevent the patient\u0026acute;s awareness of the actual treatment arm.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eSurgical Procedure\u003c/h3\u003e\n\u003cp\u003eAfter induction of anesthesia, the abdomen and genitals were disinfected and surrounded with sterile surgical drapes. An indwelling 18 Ch urine catheter (Bard Biocath\u0026reg;, BD Oslo, Norway) was inserted, and the patients were tilted in the 30-degree head-down position. All procedures were performed with the da Vinci XI\u0026reg; or da Vinci X systems (Intuitive Surgical Inc., Sunnyvale, CA, USA), using a standardized 4-arm transperitoneal 6-port approach with a 0\u0026deg; lens, a maryland bipolar forceps, monopolar curved scissors and a ProGrasp\u0026trade; forceps (Intuitive Surgical Inc., Sunnyvale, CA, USA) as previ(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The bladder was dissected downwards by entering the space of Retzius (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The bladder neck was meticulously released from the base of the prostate, before it was cut. After the division of the bladder neck was completed dorsally, the vasa deferentia were identified in the midline where they were cut, and the seminal vesicles were dissected free. Nerve-sparing was routinely performed on one or both sides, depending on whether the distance from to the tumor to the neurovascular bundle was considered adequate to avoid positive surgical margins. The length of the urethra was preserved similarly. After the anastomosis between the bladder neck and urethra was successfully completed, the specimen was extracted by a vertical, midline incision above the umbilicus. Trocar incisions were infiltrated with a total of 20 ml bupivacaine 2.5 mg/ml with adrenalin 5 \u0026micro;g/ml. The fascia of the midline incision and in the right lateral 12 mm port incision were sutured with a polydiaxon suture. The skin was closed with staples.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative recordings and pain management in the PACU\u003c/h2\u003e \u003cp\u003ePatients in both groups received oral paracetamol 1 gr every 6 hours. Morphine 2.5\u0026ndash;5 mg was administered intravenously by the PACU nurse if NRS was \u0026gt;\u0026thinsp;3. PCA was initiated as soon as the patients scored NRS\u0026thinsp;\u0026lt;\u0026thinsp;4. PCA consisted of 3 mg morphine with 15 minutes lockout time. The Bromage score was applied to test for motor blockade on admittance and after 2 hrs in the PACU.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePostoperative pain management in the ward\u003c/h3\u003e\n\u003cp\u003ePatients in both groups receive postoperatively oral paracetamol 1 gr every 6 hours. A second dose etoricoxib 90 mg was given at 07:00 on postoperative day 1. PCA morphine was continued in the ward.\u003c/p\u003e\n\u003ch3\u003eStatistics\u003c/h3\u003e\n\u003cp\u003ePrimary outcome measure was time to discharge from PACU. Secondary outcome measures were postoperative pain and opioid consumption. Repeated measures analysis of variance was applied to test for differences in NRS. The Mann\u0026ndash;Whitney U-test was used to test for time specific data analyses. The Fisher\u0026rsquo;s exact test was applied for ordinal data. P\u0026thinsp;\u0026le;\u0026thinsp;0.05 was deemed statistically significant. SPSS version 29.0 (IBM, Armonk, NY, USA) was used for all calculations and for production of graphic material.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePatients were consecutively recruited in accordance with the inclusion and exclusion criteria (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Four patients declined to participate because they were worried about potential complications related to spinal anesthesia. Included patients were treated in accordance with the study protocol, and all data were included in the final analyses.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAge, body mass index (BMI), and American Society of Anesthesiologists physical status classification system (ASA) were not significantly different between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Surgery time was equal in both groups. Patients in the spinal group needed less remifentanil compared to the placebo group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, p\u0026thinsp;=\u0026thinsp;0.01), while intraoperative dose of propofol and noradrenaline did not differ between the study groups (p\u0026thinsp;=\u0026thinsp;0.31 and p\u0026thinsp;=\u0026thinsp;0.68, respectively).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient demographics. Median (range)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpinal (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePlacebo (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (62\u0026ndash;74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (50\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (23\u0026ndash;34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (23\u0026ndash;35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA I/II/III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/15/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/15/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eASA; American Society of Anesthesiologists physical status classification system. BMI; Body mass index. Note: *Mann-Whitney U-test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIntraoperative data. Median (range)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpinal (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePlacebo (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRALP with epld\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRALP without epld\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime of surgery (minutes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e146 (74\u0026ndash;185)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e146 (77\u0026ndash;232)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal dose of propofol (mg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1664 (763\u0026ndash;2425)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1790 (1000\u0026ndash;3077)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal dose of remifentanil (\u0026micro;g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1463 (854\u0026ndash;3240)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2625 (1300\u0026ndash;4954)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal dose noradrenaline (ng)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e310 (120\u0026ndash;1300)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e230 (60\u0026ndash;790)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: *Mann-Whitney U-test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePain, discomfort and quality assessment. Median (range)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpinal (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePlacebo (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak pain score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBladder spasm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrgency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpioid consumption\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026ndash;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (0\u0026ndash;28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQoR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139 (108\u0026ndash;150)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114 (67\u0026ndash;132)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eQoR-15; Quality of recovery 15.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePatients who received spinal anesthesia were discharged earlier from the PACU (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, p\u0026thinsp;=\u0026thinsp;0.01). Repeated analyses of variance revealed that NRS decreased in both groups over time. However, analysis of between group effect showed that NRS at rest was significantly lower in the spinal group (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). A similar pattern was observed for NRS after a forced cough where pain decreased over time, while analysis of between group effect revealed lower NRS in the spinal group (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFurthermore, peak pain score and opioid consumption during the stay in the PACU were lower in the spinal group, p\u0026thinsp;=\u0026thinsp;0.007 and p\u0026thinsp;=\u0026thinsp;0.04, respectively. Patients who received spinal anesthesia reported less bladder spasm (p\u0026thinsp;=\u0026thinsp;0.02) and less urgency (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Quality of recovery-15 score was higher in the spinal group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The Bromage score was recorded without any signs of motor blockade during the stay in PACU. No other attributable side effects related to spinal anesthesia and/or intrathecal morphine were recorded. All patients were discharge from hospiat on postoperative day 1, except from 1 patient in each group who were discharge on day two due to poor logistics.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eData from the current study revealed significant benefits from spinal anesthesia as an adjunct to general anesthesia in patients undergoing robotic assisted laparoscopic prostatectomy. Improved pain relief and less discomfort facilitated faster recovery, and more satisfied patients in the spinal group compared to patients in the placebo group.\u003c/p\u003e \u003cp\u003eA multimodal approach for pain management is fundamental in all ERAS protocols and effective analgesia without delayed recovery is the primary goal. ERAS involves a series of evidence-based procedures for optimizing perioperative treatment with the aim of reducing the physical and psychological stresses of surgical trauma and thus accelerating patients\u0026rsquo; recovery(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Lin et al tested this concept in prostate cancer patients who were undergoing laparoscopic radical prostatectomy(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). They found that implementation of an ERAS protocol effectively accelerated patient rehabilitation and reduced length of stay (LOS) and hospitalization costs. The ERAS concept has been implemented in our hospital for many years, introduced and lead by Professor Arthur Revhaug who was a co-founding member of the ERAS Study Group and later the ERAS\u0026reg; Society(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). In the current study all patients received treatment in accordance with ERAS recommendations including preoperative counselling, carbohydrate fluid loading, targeted intraoperative fluid resuscitation and temperature control, no drains, multimodal analgesics, early mobilization, and early postoperative drinking and eating. Despite all these measures, patients in the placebo group suffered from significant postoperative pain and discomfort. Median and range of NRS on activity after 2 hours in PACU was 5 (\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) compared to the spinal group 2(0\u0026ndash;4). Furthermore, spinal anesthesia was very effective to alleviate discomfort related to bladder spasm and urgency. Patients in the spinal group received less remifentanil during anesthesia, which is likely due to the analgetic effects of intrathecal morphine and bupivacaine. Furthermore, there was less need for rescue pain medication in the spinal group. These findings are very much in line with a previous study where we showed the potential benefit of spinal anesthesia as an adjunct to general anaesthesia after laparoscopic abdominoperineal rectal amputation(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAdministration of intrathecal morphine at a lower dose (100 \u0026micro;g) has consistently been reported to be safe practice without causing respiratory complications(\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Concerns related to the use of intrathecal morphine are most likely rooted in older studies in which higher doses of morphine were administrated, and often in clinical settings with limited access to adequate monitoring. The aim of using 100 \u0026micro;g of intrathecal morphine in the current study was to provide effective analgesia, while ensuring patient safety without the need to intensify clinical monitoring. Two interesting studies are relevant to discuss in this context. Koning et al combined 300 \u0026micro;g intrathecal morphine with 12.5 mg bupivacaine(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), while Shim et al combined 200 \u0026micro;g intrathecal morphine with 7.5 mg bupivacaine(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Both studies demonstrated lower postoperative pain scores and reduced in-hospital cumulative morphine consumption, and neither reported any major respiratory or cardiovascular complications. The only principal adverse effect observed was a modestly increased incidence of pruritus in the 300\u0026micro;g group(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Furthermore, Shim et al did not assess bladder spasm or urgency symptoms and quality of patient recovery was not reported. Anyway, data from both studies demonstrated the analgetic potency of intrathecal morphine in patients undergoing laparoscopic prostate surgery. Despite current evidence, neither the ERAS\u0026reg; Society nor PROSPECT recommend spinal analgesia as an adjunct to general anesthesia for robotic assisted laparoscopic prostatectomy. We believe it is time to review and update these recommendations, yet knowledge gaps related to dose\u0026ndash;response parameters and potential ceiling effect of neuraxial morphine remain and should be studied in future clinical trials. PROSPECT arguments against the use of intrathecal morphine as first-line analgesia in minimally invasive prostatectomy refers to the risk of serious potential side effects, limited evidence for low-dose regimens, and unclear analgesic duration(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Co-administration of other drugs may have also contributed to some earlier reports of adverse events after a single shot spinal. Our decision to combine 100 \u0026micro;g of intrathecal morphine with 7.5 mg of hyperbaric bupivacaine was guided by evidence from studies in cesarean delivery and minimally invasive colorectal surgery, where low-dose intrathecal opioids provide effective analgesia without side effects(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The rationale for employing a low dose of bupivacaine was to potentiate the analgesic effect of morphine, particularly in the intraoperative period, while minimizing the risk of residual motor block during the immediate postoperative recovery period.\u003c/p\u003e \u003cp\u003eIn recent years, there has been an increasing interest in the use of abdominal wall blocks for pain relief after caesarean delivery and laparoscopic surgery(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). However, the quality of analgesia provided by intrathecal morphine has consistently proven superior, reinforcing its role as a valuable component of multimodal analgesic strategies that combine efficacy, safety, and practicality in routine clinical practice. Although spinal anesthesia is well established in clinical practice, several issues remain to be studied. Different drug combinations and dosing open the possibility of a true \u0026ldquo;multimodal spinal anesthesia\u0026rdquo;, further enhancing its potential and versatility. Mastering spinal anesthesia is invaluable in the setting of a busy contemporary hospital, but it also remains feasible and highly relevant in low-resource environments. The evolution of anesthetic practice should therefore consider not only technological advances but also the preservation and refinement of simple, effective, and universally applicable techniques such as spinal anesthesia, which is not time-consuming, easy to learn, and largely independent of other technologies.\u003c/p\u003e \u003cp\u003eLimitations to this study include the single-center design and the relatively small sample size. We did not perform a dose-finding trial, so ED₅₀ and ED₉₀ for intrathecal morphine in this population remains to be studied. Follow-up was limited to the immediate postoperative period, and longer-term outcomes were not assessed. Despite these limitations, we believe the current study adds valuable data in support of using low-dose spinal morphine for postoperative pain relief after robotic assisted laparoscopic prostatectomy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOptimizing perioperative analgesia is a priority in modern anesthesiology, balancing effective pain relief against potential adverse side effects. In the current study, spinal anesthesia as an adjunct to general anesthesia enhanced recovery after surgery and improved patient-reported outcomes following robotic assisted radical prostatectomy. Although PROSPECT guidelines currently advise against spinal morphine, our findings support its feasibility, safety, and potential clinical benefit. Low-dose spinal morphine merits consideration as part of multimodal analgesic strategies for prostatectomy, yet further prospective studies are warranted in order to define optimal dosing and establish its role in contemporary perioperative pain management.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eERAS; Enhanced Recovery After Surgery\u003c/p\u003e\n\u003cp\u003eNRS; Numeric Rating Scale\u003c/p\u003e\n\u003cp\u003ePACU; Post Anesthesia Care Unit\u003c/p\u003e\n\u003cp\u003ePROSPECT; Procedure Specific Postoperative Pain Management\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eQoR-15; Quality of Recovery-15\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe research protocol was approved by the regional committee for medical and health research ethics in Norway (REC 866656) and by the Institutional Regulatory Board (Record ID 2025/3168-6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study was registered at https://clinicaltrials.gov (NCT06860893) on February 28\u003csup\u003eth\u003c/sup\u003e, 2025, before inclusion of the first patient. Unfortunately, the primary outcome parameter was wrongly stated in the original submission to Clinical Trials Gov. This mistake was later corrected and documented in the Clintrials.gov file history. We apologize for this mistake. \u0026nbsp;\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e \u003cp\u003eThe research protocol was approved by the regional committee for medical and health research ethics in Norway (REC 866656), \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eUiT- The Arctic University of Norway, Postbox 6050 Langnes, 9037 Troms\u0026oslash;, Norway\u003c/span\u003e and by the Institutional Regulatory Board (Record ID 2025/3168-6), University Hospital of North Norway, 9038 Troms\u0026oslash;, Norway. Written informed consent was obtained from all participants.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eOpen access funding was provided by UiT The Arctic University of Norway.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.A and L.M.Y. had the original idea. M.A, A.G.H., and D.J. performed the study. The manuscript was drafted by all authors. All authors contributed to, read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank all patients who participated. We also thank the nurses and doctors who were involved in the treatment and care of the patients.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data and material will be made available on reasonable request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRawla P. Epidemiology of Prostate Cancer. World J Oncol. 2019;10(2):63\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCornford P, van den Bergh RCN, Briers E, Van den Broeck T, Brunckhorst O, Darraugh J, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2024;86(2):148\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAarsaether E, Roaldsen M, Knutsen T, Patel HR, Soltun B. Improvement in early continence after introduction of periurethral suspension stitch in robotic prostatectomy. J Robot Surg. 2021;15(5):679\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLemoine A, Witdouck A, Beloeil H, Bonnet F, Anaesthesia PWGOTESOR, Pain T. PROSPECT guidelines update for evidence-based pain management after prostatectomy for cancer. Anaesth Crit Care Pain Med. 2021;40(4):100922.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDobbs RW, Shahait M, Lee DI. Response to: Williams, Kotamarti, and Schulman re: Outpatient Robot-Assisted Radical Prostatectomy: Are Patients Ready for Same-Day Discharge? by Dobbs et al. J Endourol. 2021;35(2):235.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoning MV, de Vlieger R, Teunissen AJW, Gan M, Ruijgrok EJ, de Graaff JC, et al. The effect of intrathecal bupivacaine/morphine on quality of recovery in robot-assisted radical prostatectomy: a randomised controlled trial. Anaesthesia. 2020;75(5):599\u0026ndash;608.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNuri Deniz M, Erhan E, Ugur G. Intrathecal morphine reduces postoperative tramadol consumption in patients undergoing radical retropubic prostatectomy: a randomized trial. Eur Rev Med Pharmacol Sci. 2013;17(6):834\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRawal N. Intrathecal opioids for the management of post-operative pain. Best Pract Res Clin Anaesthesiol. 2023;37(2):123\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLarsen M, Giske A, Roaldsen M, Gullan D, Aarsaether E. Robotic assisted simple prostatectomy mitigates perioperative morbidity compared to open simple prostatectomy - a single institution report. BMC Urol. 2024;24(1):221.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeldheiser A, Aziz O, Baldini G, Cox BP, Fearon KC, Feldman LS, et al. Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia practice. Acta Anaesthesiol Scand. 2016;60(3):289\u0026ndash;334.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin C, Wan F, Lu Y, Li G, Yu L, Wang M. Enhanced recovery after surgery protocol for prostate cancer patients undergoing laparoscopic radical prostatectomy. J Int Med Res. 2019;47(1):114\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFearon KC, Ljungqvist O, Von Meyenfeldt M, Revhaug A, Dejong CH, Lassen K, et al. Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection. Clin Nutr. 2005;24(3):466\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAntunes M, Baumgartel A, Gjessing PF, Ytrebo LM. Spinal Anaesthesia as an Adjunct to General Anaesthesia for Laparoscopic Abdominoperineal Rectal Amputation. J Pain Res. 2023;16:1855\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTee ZH, Tsoi EHC, Lee Q, Wong YS, Gibson A, Parsons N et al. Intrathecal Morphine and Post-Operative Pain Relief in Robotic Surgeries: A Systematic Review and Meta-Analysis. J Clin Med. 2023;13(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoning MV, Klimek M, Rijs K, Stolker RJ, Heesen MA. Intrathecal hydrophilic opioids for abdominal surgery: a meta-analysis, meta-regression, and trial sequential analysis. Br J Anaesth. 2020;125(3):358\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoning MV, Reussien E, Vermeulen BAN, Zonneveld S, Westerman EM, de Graaff JC, et al. Serious Adverse Events after a Single Shot of Intrathecal Morphine: A Case Series and Systematic Review. Pain Res Manag. 2022;2022:4567192.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShim JW, Cho YJ, Moon HW, Park J, Lee HM, Kim YS, et al. Analgesic efficacy of intrathecal morphine and bupivacaine during the early postoperative period in patients who underwent robotic-assisted laparoscopic prostatectomy: a prospective randomized controlled study. BMC Urol. 2021;21(1):30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHussain N, Brull R, Thaete L, Fuller S, D'Souza RS, Mankinen-Abdallah Y, et al. The analgesic effects of novel fascial plane blocks compared with intrathecal morphine after Caesarean delivery: a systematic review and meta-analysis. Br J Anaesth. 2025;134(5):1415\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"buro","sideBox":"Learn more about [BMC Urology](http://bmcurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/buro/default.aspx","title":"BMC Urology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Prostatectomy, Cancer, Pain, Spinal anesthesia, Enhanced recovery","lastPublishedDoi":"10.21203/rs.3.rs-8689169/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8689169/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eNovel surgical techniques have facilitated faster recoveries after radical laparoscopic prostatectomy, yet abdominal pain and urinary catheter related discomfort remain a clinical challenge. We hypothesised that spinal anesthesia as an adjunct to general anesthesia would facilitate faster recovery and less postoperative pain and discomfort compared to standard medical treatment.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA double-blind randomised study was designed with one group (n\u0026thinsp;=\u0026thinsp;15) allocated to general anesthesia and intrathecal injection of hyperbaric bupivacaine (7.5 mg)/spinal morphine (100 \u0026micro;g), while controls (n\u0026thinsp;=\u0026thinsp;15) received general anesthesia and a sham spinal procedure before they underwent robotic prostatectomy. Two hours before induction of anesthesia, all patients received orally paracetamol 1 g, dexamethasone 8 mg and etoricoxib 90 mg. General anesthesia was performed using remifentanil, propofol and rocuronium. Postoperative analgesia consisted of intravenous morphine via a patient-controlled device, oral etoricoxib 90 mg x 1 and paracetamol 1 gr x 4. Primary outcome measure was time to discharge from the post anesthesia care unit (PACU). Secondary outcome measures were postoperative pain and opioid consumption.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePatients who received spinal anesthesia were discharged earlier from the PACU (p\u0026thinsp;=\u0026thinsp;0.010) and reported less pain on admittance to the PACU and after 2 hrs (p\u0026thinsp;=\u0026thinsp;0.019 and p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively). Furthermore, peak pain score (p\u0026thinsp;=\u0026thinsp;0.007) and opioid consumption (p\u0026thinsp;=\u0026thinsp;0.04) were lower in the spinal group during the PACU stay. Patients who received spinal anesthesia reported less discomfort related to bladder spasm (p\u0026thinsp;=\u0026thinsp;0.021) and urgency (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Quality of recovery-15 score was higher in the spinal group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No attributable side effects related to spinal anesthesia and intrathecal morphine were observed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eSpinal anesthesia as an adjunct to general anesthesia facilitated faster recovery, better pain relief and less discomfort compared to standard medical treatment after robotic assisted laparoscopic prostatectomy. Patients in the spinal group were more satisfied as assessed by QoR-15.\u003c/p\u003e","manuscriptTitle":"Spinal anesthesia as an adjunct to general anesthesia for robotic assisted laparoscopic prostatectomy – a randomised placebo-controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-27 16:23:03","doi":"10.21203/rs.3.rs-8689169/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-02-25T08:32:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-23T14:33:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-05T21:47:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-03T11:20:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Urology","date":"2026-02-03T10:15:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"buro","sideBox":"Learn more about [BMC Urology](http://bmcurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/buro/default.aspx","title":"BMC Urology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5df6b06d-516b-4176-aa70-fe22e68810fe","owner":[],"postedDate":"February 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-27T16:23:03+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-27 16:23:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8689169","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8689169","identity":"rs-8689169","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}