The impact of perioperative nonsteroidal anti-inflammatory drugs on the postoperative outcomes of spinal surgery: a meta-analysis of 23 randomized controlled trials.

In recent years, nonsteroidal anti-inflammatory drug (NSAIDs), which are considered to affect the prognosis of spinal surgery, have been widely used in perioperative analgesia in spinal surgery, but the relationship between these two factors remains unclear. The purpose of this study was to explore the effect of perioperative use of NSAIDs on the prognosis of patients treated with spinal surgery. We systematically searched PubMed, Embase, and Cochrane Library for relevant articles published on or before July 14, 2023. We used a random-effect model for the meta-analysis to calculate the standardized mean difference (SMD) with a 95% confidence interval (CI). Sensitivity analyses were conducted to analyze stability. A total of 23 randomized clinical trials including 1457 participants met the inclusion criteria. Meta-analysis showed that NSAIDs were significantly associated with postoperative morphine use (mg) (SMD = -0.90, 95% CI -1.12 to -0.68) and postoperative pain (SMD = -0.71, 95% CI -0.85 to -0.58). These results were further confirmed by the trim-and-fill procedure and leave-one-out sensitivity analyses. The current study shows that perioperative use of NSAIDs appears to be an important factor in reducing postoperative pain and morphine use in patients undergoing spinal surgery. However, well-designed, high-quality randomized controlled trials (RCTs) are still required.

Pattern of Prescribing Analgesics and Their Response in Cancer Patients Attending Outpatient Department of Palliative Care Service in Two Teaching Hospitals of Bangladesh.

Palliative care is a valued aspect of clinical care which is an urgent humanitarian need for people worldwide with cancer and other chronic fatal diseases. Patients experience many different symptoms including severe pain in advanced cancer. Palliative care focuses on relief from symptoms, pain and stress by using different analgesics and adjuvant. The goal of palliative care is to improve the quality of life. So, this prospective observational study was carried out to assess pattern of drugs used and their response to pain in cancer patients attending out-patient department of palliative care service in two teaching hospitals of Bangladesh. One hundred forty (140) cancer patients were purposively selected who attended in out-patient department of palliative care unit in Bangabandhu Sheikh Mujib Medical University (BSMMU) and Dhaka Medical College Hospital (DMCH) from July 2018 to June 2019. Outcome variables were commonly presenting complaints, pain intensity, commonly prescribed drugs and analgesic prescription according to WHO three-step analgesic ladder, etc. The mean age ±SD of the respondents was 51.30±15.38 years, male-female ratio 1:1. Common sites of cancer were alimentary origin (20.0%), genitourinary system (17.86%), hepatobiliary system (11.43%), respiratory system (10.71%). The prescribed drugs were analgesics (96.4%), PPIs (74.3%), laxatives (62.1%), anti-emetics (38.6%), multivitamins (32.9%), H2 antagonists (17.1%), sedatives (17.1%), and corticosteroids (8.6%). Level 1 analgesics (Paracetamol or other NSAIDs) were prescribed to 42.65%, level 2 analgesics (Tramadol) were prescribed to 50.00% patients and level 3 analgesics (Morphine) were prescribed to 51.42% patients. The relation between and receiving three levels of analgesic prescriptions was statistically significant. The association between level of analgesic prescription was significant with site of cancer (p<0.001) and intensity of pain (p<0.001). This study showed that morphine was prescribed to more than half of the patients. Other level of analgesics were also used either single or in combination. Younger and male patients were treated more with level III analgesics. Prescribing analgesics were dependent on sites of cancer and intensity of pain.

Effect of a Multidisciplinary Review Panel on Daily Morphine Milligram Equivalents for Patients With Chronic Pain.

INTRODUCTION/OBJECTIVE: Physicians and other health care professionals are challenged regularly to balance managing pain for patients with chronic pain receiving chronic opioid therapy (COT) with following the national guidelines and standards regarding daily morphine milligram equivalents (MME). This quality improvement project aimed to determine the effect of referral to a multidisciplinary review panel on daily MME for patients receiving COT for chronic pain. METHODS: This quality improvement project included patients who had an established relationship with a primary care or community internal medicine clinician at a large health care organization and were referred to a newly created multidisciplinary review panel for their recommendations regarding treatment of pain. Criteria for patient referral were diagnosis of a chronic, painful condition, and use of chronic opioid medications. These patients were selected and referred at the discretion of their primary care clinician from January 2, 2019, through December 31, 2020. Data for this project were collected at the time of initial referral to the panel and 6 months after recommendations. The daily MME were assessed at the 2 time points. RESULTS: Thirteen patients were referred to the review panel during the project period. The median daily MME at the time of referral was 180. Daily MME decreased by a median of 14 MME after 6 months. The MME did not increase during the project period for any participants. CONCLUSIONS: Referral of patients receiving COT to a multidisciplinary review panel may reduce their daily opioid dose.

The Dose-Response Relationship between Opioid Agonist Therapy and Alterations in Pain Pathways in Patients with Opioid Use Disorders: A Cross-Sectional Study.

INTRODUCTION: The administration of opioids can be followed by enduring neuroplastic changes in the peripheral and central nervous systems. This remodeling can lead to opioid-induced hyperalgesia, causing an increased sensitivity to painful stimuli. The description of opioid-induced changes in the somatosensory system has seldom been described in the setting of opioid agonist therapy in the treatment of opioid use disorders, and the few existing reports provide no guidance with respect to the effect of varied doses or substances. OBJECTIVE: The aim of the present study was to assess alterations of pain pathways among patients receiving opioid agonist therapy and to elucidate the dose-response relationship. METHODS: This study was planned as cross-sectional in an outpatient clinic in Graz, Austria. Patients receiving opioid agonist therapy for opioid use disorders (including methadone, levomethadone, buprenorphine, and extended-release morphine) were asked to fill out a questionnaire, including the central sensitization inventory. A battery of somatosensory system assessments was then performed. RESULTS: A total of 120 patients participated (85 men/35 women). The mean oral morphine milligram equivalent (MME) was 694 ± 249 mg/day. Our study found significant alterations in pain perception, conditioned pain modulation, and wind-up. We demonstrated a moderate dose-response relationship between high-dose opioids and markers of central sensitization. CONCLUSION: The present trial demonstrates the clear effects of opioid agonist therapy on the somatosensory system. Both central sensitization and descending pain modulation are negatively affected by high doses of opioids and our data elucidate a moderate dose-response relationship for these phenomena.

Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial.

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis. METHODS: The PACIFY COUGH study is a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial done in three specialist centres in the UK. Eligible patients aged 40-90 years had a diagnosis of idiopathic pulmonary fibrosis within 5 years, self-reported cough (lasting >8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher. Patients were randomly assigned (1:1) to placebo twice daily or controlled-release morphine 5 mg orally twice daily for 14 days followed by crossover after a 7-day washout period. Patients were randomised sequentially to a sequence group defining the order in which morphine and placebo were to be given, according to a computer-generated schedule. Patients, investigators, study nurses, and pharmacy personnel were masked to treatment allocation. The primary endpoint was percentage change in objective awake cough frequency (coughs per h) from baseline as assessed by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. Safety data were summarised for all patients who took at least one study drug and did not withdraw consent. This study was registered at ClinicalTrials.gov, NCT04429516, and has been completed. FINDINGS: Between Dec 17, 2020, and March 21, 2023, 47 participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment. Mean age was 71 (SD 7·4) years, and 31 (70%) of 44 participants were male and 13 (30%) were female. Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L (SD 0·76), mean predicted FVC was 82% (17·3), and mean predicted diffusion capacity of carbon monoxide was 48% (10·9). Of the 44 patients who were randomised, 43 completed morphine treatment and 41 completed placebo treatment. In the intention-to-treat analysis, morphine reduced objective awake cough frequency by 39·4% (95% CI -54·4 to -19·4; p=0·0005) compared with placebo. Mean daytime cough frequency reduced from 21·6 (SE 1·2) coughs per h at baseline to 12·8 (1·2) coughs per h with morphine, whereas cough rates did not change with placebo (21·5 [SE 1·2] coughs per h to 20·6 [1·2] coughs per h). Overall treatment adherence was 98% in the morphine group and 98% in the placebo group. Adverse events were observed in 17 (40%) of 43 participants in the morphine group and six (14%) of 42 patients in the placebo group. The main side-effects of morphine were nausea (six [14%] of 43 participants) and constipation (nine [21%] of 43). One serious adverse event (death) occurred in the placebo group. INTERPRETATION: In patients with cough related to idiopathic pulmonary fibrosis, low dose controlled-release morphine significantly reduced objective cough counts over 14 days compared with placebo. Morphine shows promise as an effective treatment to palliate cough in patients with idiopathic pulmonary fibrosis, and longer term studies should be the focus of future research. FUNDING: The Jon Moulton Charity Trust.

Low dose lofexidine for medically directed outpatient opioid tapering in adults with chronic pain: a prospective case series.

BACKGROUND: In adults with chronic pain, mild-to-moderate withdrawal symptoms during medically directed opioid tapering in the outpatient setting may not be accompanied by hypertension or tachycardia. This clinical scenario could limit the use of lofexidine at dosages reported in clinical trials of opioid withdrawal precipitated by abrupt opioid discontinuation. Thus, the primary aim of this prospective case series is to describe the use of low dose lofexidine for opioid withdrawal in patients with chronic pain undergoing medically directed opioid tapering in an outpatient setting. METHODS: Six patients (white 5, Latino 1) admitted to an outpatient interdisciplinary pain rehabilitation program met inclusion and exclusion criteria. Patients self-selected to undergo medically directed opioid tapering, and the medication the patients were prescribed upon admission was used in the taper schedule. Upon initiation of the opioid taper, patients received 0.18 mg of lofexidine every 6 hours. RESULTS: Five of the six patients were women, and the median morphine milligram equivalents at baseline were 36.9. The median taper duration was 15 days, and the median duration of lofexidine administration was 14 days. Withdrawal scores were mild throughout the taper in four patients, and two patients with fibromyalgia experienced single episodes of moderately severe withdrawal symptoms at the median morphine milligram equivalent midpoint of the taper. No hypotension or sustained bradycardia were observed, and no adverse effects related to lofexidine were reported. CONCLUSION: The observations from this prospective case series suggest that low-dose lofexidine may be a feasible adjunct medication to attenuate withdrawal symptoms in adults with chronic pain undergoing outpatient opioid tapering.

Effect of opioid-free anesthesia on post-operative period in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a propensity score matched study.

BACKGROUND: Postoperative pain after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is important. It appears essential to reduce postoperative pain and morphine consumption. METHODS: Retrospective study in a university hospital comparing patient benefiting from CRS-HIPEC under opioid-free anesthesia (OFA; dexmedetomidine) to those anesthetized with opioid anesthesia (OA; remifentanil) using a propensity score matching method. The main objective was the impact of OFA on postoperative morphine consumption in the first 24 h after surgery. RESULTS: 102 patients were included, matching on the propensity score allowed selecting 34 unique pairs analyzed. Morphine consumption was lower in the OFA group than in the OA group (3.0 [0.00-11.0] mg/24 h vs. 13.0 [2.5-25.0] mg/24 h; p = 0.02). In multivariable analysis, OFA was associated with a reduction of 7.2 [0.5-13.9] mg of postoperative morphine (p = 0.04). The rate of renal failure with a KDIGO-score > 1 was lower in the OFA group than in the OA group (12% vs. 38%; p = 0.01). There was no difference between groups concerning length of surgery/anesthesia, norepinephrine infusion, volume of fluid therapy, post-operative complications, rehospitalization or ICU readmission within 90 days, mortality, and postoperative rehabilitation. CONCLUSION: Our results suggest that OFA for CRS-HIPEC patients appears safe and is associated with less postoperative morphine use and acute kidney injury.

The contribution of pain catastrophizing, depression and anxiety symptoms among patients with persistent pain and opioid misuse behaviours.

BACKGROUND: Anxiety, depression and pain catastrophizing are independently associated with risk of opioid misuse in patients with persistent pain but their relationship to current opioid misuse, when considered together, is poorly understood. This study will assess the relative contribution of these modifiable, and distinct psychological constructs to current opioid misuse in patients with persistent pain. METHODS: One hundred and twenty-seven patients referred to a specialized opioid management clinic for prescription opioid misuse within a tertiary pain service were recruited for this study. The Pain Catastrophizing Scale, Depression, Anxiety and Stress Scales and the Current Opioid Misuse Measure were administered pre-treatment. Pain severity and morphine equivalent dose based on independent registry data were also recorded. RESULTS: Higher levels of pain catastrophizing, depression, and anxiety were significantly associated with higher current opioid misuse (r = .475, 0.599, and 0.516 respectively, p < .01). Pain severity was significantly associated with pain catastrophizing (r = .301, p < .01). Catastrophizing, depression, and anxiety explained an additional 11.56% of the variance (R2 change = 0.34, p < .01) over and above age, gender, pain severity and morphine equivalent dose. Depression was the only significant variable at Step 2 (ß = 0.62, p < .01). CONCLUSION: Findings show that in a sample of people with persistent pain referred for treatment for opioid misuse, depression contributes over and above that of anxiety and pain catastrophizing. Theoretical and clinical practice implications are presented.

Naloxone-Prescribing Practices in a Freestanding Rehabilitation Hospital.

OBJECTIVE: The study aims to determine whether Physical Medicine & Rehabilitation physicians offer naloxone per the Centers for Disease Control and Prevention Guidelines to patients at the highest risk of complications from opioid treatment and whether there is a difference between inpatient and outpatient naloxone prescribing. DESIGN: A retrospective chart review on 389 adults (outpatient n = 166; inpatient n = 223) from May 4 to May 31, 2022, at an academic rehabilitation hospital. Prescribed medications and comorbidities were evaluated to determine whether Centers for Disease Control and Prevention criteria for offering naloxone were met and whether naloxone was offered. RESULTS: One hundred twenty-nine opioid prescriptions were written for 102 outpatients; 61 qualified for naloxone (morphine milliequivalent range = 10-1080, mean = 158.08). On inpatient, 68 patients received 86 opioid prescriptions; 35 qualified for naloxone (morphine milliequivalent range = 3.75-246, mean = 62.36). Overall, there was a significantly lower rate of opioid prescriptions for inpatients (30.49%) than outpatients (61.45%) ( P < 0.0001), a nonsignificant lower rate of inpatient (51.47%) than outpatient (59.80%) "at-risk" prescriptions ( P = 0.351), and a weakly significant lower rate of naloxone prescribing for inpatient (2.86%) than outpatient visits (8.20%) ( P < 0.0519). CONCLUSIONS: At this rehabilitation hospital, there was a low rate of naloxone prescribing by inpatient and outpatient providers, with a higher rate occurring in the outpatient than inpatient setting. More research is needed to understand this prescribing trend to determine potential interventions.

Eliminating the benzos: A benzodiazepine-sparing approach to preventing and treating alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal syndrome (AWS) represents significant cost to the hospitalized trauma population from a clinical and financial perspective. Historically, AWS has been managed with benzodiazepines. Despite their efficacy, benzodiazepines carry a heavy adverse effect profile. Recently, benzodiazepine-sparing protocols for the prophylaxis and treatment of AWS have been used in medical patient populations. Most existing benzodiazepine-sparing protocols use phenobarbital, while ours primarily uses gabapentin and clonidine, and no such protocol has been developed and examined for safety and efficacy specifically within a trauma population. METHODS: In December of 2019, we implemented our benzodiazepine-sparing protocol for trauma patients identified at risk for alcohol withdrawal on admission. Trauma patients at risk for AWS admitted to an academic Level 1 trauma center before (conventional) and after (benzodiazepine-sparing [BS]) protocol implementation were compared. Outcomes examined include morphine milligram equivalent dosing rates and lorazepam equivalent dosing rates as well as the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scores, hospital length of stay, intensive care unit length of stay, and ventilator days. RESULTS: A total of 387 conventional and 134 benzodiazepine sparing patients were compared. Injury Severity Score (13 vs. 16, p = 0.10) and admission alcohol levels (99 vs. 149, p = 0.06) were similar. Patients in the BS pathway had a lower maximum daily CIWA-Ar (2.7 vs. 1.5, p = 0.04). While mean morphine milligram equivalent per day was not different between groups (31.5 vs. 33.6, p = 0.49), mean lorazepam equivalents per day was significantly lower in the BS group (1.1 vs. 0.2, p < 0.01). Length of stay and vent days were not different between the groups. CONCLUSION: Implementation of a benzodiazepine-sparing pathway that uses primarily clonidine and gabapentin to prevent and treat alcohol withdrawal syndrome in trauma patients is safe, reduces the daily maximum CIWA-Ar, and significantly decreases the need for benzodiazepines. Future studies will focus on outcomes affected by avoiding AWS and benzodiazepines in the trauma population. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Synthesis, molecular docking, electrochemical and fluorimetric analysis of new caffeic and cinnamic acid-conjugated hemorphin derivatives designed as potential anticonvulsant and antinociceptive agents.

Based on the pharmacophore model of opioid receptors, our team recently synthesized a series of short-chain hemorphin peptide analogs containing non-natural amino acids. They demonstrated anticonvulsant and antinociceptive activity with low neurotoxicity. In the present study, a series of novel bioconjugates of N-modified hemorphin analogs containing second pharmacophore cinnamic acids (CA) or caffeic (KA) were synthesized by a traditional solid-phase Fmoc chemistry method for peptide synthesis. Electrochemical and fluorimetric analysis, in vivo anticonvulsant and antinociceptive activity in mice were conducted on the compounds. The three CA acid- (H4-CA, H5-CA, and H7-CA) and three KA acid- (H4-KA, H5-KA, and H7-KA) conjugated hemorphin derivatives exhibited potency at the highest doses of 2 µg/5 µl, administered by intracerebroventricular (icv) mode, against seizure spread in the maximal electroshock test (MES) in mice. The KA-conjugated H5-KA derivate, at the lowest dose, was the only compound that suppressed clonic seizures in the subcutaneous pentylenetetrazol (scPTZ) test. Except for the H5-CA, all tested CA acid- and KA acid-conjugated peptide derivates had the potency to increase the latency for clonic seizures in a dose-dependent mode. The activity against the psychomotor seizures in the 6-Hz test was detected only for the H4-CA (0.5 µg) and H4-KA (0.5 µg and 1 µg), respectively. All investigated peptides showed a more pronounced antinociceptive effect in the "intraplantar formalin" test compared to the "hot plate" test. Shorter chain analogs showed a better antinociceptive profile against tonic pain. The data suggest a DOR and KOR-mediated mechanism of action. According to the docking analysis, H7-CA showed a different antinociceptive profile than other investigated peptides. The novel peptide derivates did not exhibit neurotoxicity in the rotarod test. Our findings suggest that conjugated CA and KA morphine peptides can be used to develop novel morphine-related analogs with anticonvulsant and antinociceptive activity.

Postoperative analgesic options after spine surgery: finding the optimal treatment strategies.

INTRODUCTION: Spine surgery is one of the most common types of surgeries performed in the United States; however, managing postoperative pain following spine surgery has proven to be challenging. Patients with spine pathologies have higher incidences of chronic pain and resultant opioid use and potential for tolerance. Implementing a multimodal plan for postoperative analgesia after spine surgery can lead to enhanced recovery and outcomes. AREAS COVERED: This review presents several options for analgesia following spine surgery with an emphasis on multimodal techniques to best aid this specific patient population. In addition to traditional therapeutics, such as acetaminophen, non-steroidal anti-inflammatory medications, and opioids, we discuss intrathecal morphine administration and emerging regional anesthesia techniques. EXPERT OPINION: Several adjuncts to improve analgesia following spine surgery are efficacious in the postoperative period. Intrathecal morphine provides sustained analgesia and can be instilled intraoperatively by the surgical team under direct visualization. Local anesthetics deposited under ultrasound guidance by an anesthesiologist trained in regional techniques also provide the opportunity for single injections or continuous analgesia via an indwelling catheter.

Effect of magnesium sulfate perioperative infusion on postoperative catheter-related bladder discomfort in male patients undergoing laparoscopic radical resection of gastrointestinal cancer: a prospective, randomized and controlled study.

BACKGROUND: Laparoscopic radical resection of gastrointestinal cancer is associated with a high incidence of postoperative catheter-related bladder discomfort (CRBD). Studies on the benefits of magnesium sulfate intravenous infusion during the perioperative period post-laparoscopic surgery are yet lacking. METHODS: A total of 88 gastrointestinal cancer male patients scheduled for laparoscopic radical resection were randomly divided into two groups: normal saline (control) and magnesium. In the magnesium group, a 40 mg/kg loading dose of intravenous magnesium sulfate was administered for 10 min just after the induction of anesthesia, followed by continuous intravenous infusion of 15 mg/kg/h magnesium sulfate until the end of the surgery; the control group was administered the same dose of normal saline. Subsequently, 2 µg/kg sufentanil was continuously infused intravenously by a postoperative patient-controlled intravenous analgesia (PCIA) device. The primary outcome was the incidence of CRBD at 0 h after the surgery. The secondary outcomes included incidence of CRBD at 1, 2, and 6 h postsurgery, the severity of CRBD at 0, 1, 2, and 6 h postsurgery. Remifentanil requirement during surgery, sufentanil requirement within 24 h postsurgery, the postoperative numerical rating scale (NRS) score at 48 h after the surgery, magnesium-related side effects and rescue medication (morphine) requirement were also assessed. RESULTS: The incidence of CRBD at 0, 1, 2, and 6 h postoperatively was lower in the magnesium group than the control group (0 h: P = 0.01; 1 h: P = 0.003; 2 h: P = 0.001; 6 h: P = 0.006). The incidence of moderate to severe CRBD was higher in the control group at postoperative 0 and 1 h (0 h: P = 0.002; 1 h: P = 0.028), remifentanil requirement during surgery were significantly lower in the magnesium group than the control group. Sufentanil requirements during the 24 h postoperative period were significantly lower in the magnesium group than the control group. The NRS score was reduced in the magnesium group compared to the control group in the early postoperative period. Magnesium-related side effects and rescue medication (morphine) did not differ significantly between the two groups. CONCLUSIONS: Intravenous magnesium sulfate administration reduces the incidence and severity of CRBD and remifentanil requirement in male patients undergoing radical resection of gastrointestinal cancer. Also, no significant side effects were observed. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2100053073. The study was registered on 10/11/2021.

Long-term, continuous infusion of single-agent dinutuximab beta for relapsed/refractory neuroblastoma: an open-label, single-arm, Phase 2 study.

BACKGROUND: Short-term infusions of dinutuximab beta plus isotretinoin and cytokines administered in previous immunotherapy studies in neuroblastoma were associated with severe pain. Here, long-term, continuous infusion of single-agent dinutuximab beta was evaluated in patients with relapsed/refractory neuroblastoma. METHODS: In this open-label, single-arm, Phase 2 study, patients with either refractory or relapsed high-risk neuroblastoma received dinutuximab beta by continuous infusion over 10 days of each cycle, for up to five cycles. The primary endpoint was objective response rate 24 weeks after the end of cycle 5. Secondary endpoints included adverse events, intravenous morphine use, best response, duration of response, and three-year progression-free and overall survival. RESULTS: Of the 40 patients included, 38 had evaluable response. Objective response rate was 26% and best response rate 37%. Median duration of response was 238 days (IQR 108-290). Three-year progression-free and overall survival rates were 31% (95% CI 17-47) and 66% (95% CI 47-79), respectively. Prophylactic intravenous morphine use and duration of use decreased with increasing cycles. The most common grade 3 treatment-related adverse events were pain, diarrhea, and hypokalemia. CONCLUSION: Long-term continuous infusion of single-agent dinutuximab beta is tolerable and associated with clinically meaningful responses in patients with relapsed/refractory high-risk neuroblastoma. CLINICAL TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT02743429) and EudraCT (2014-000588-42).

Ropivacaine-Epinephrine-Clonidine-Ketorolac Cocktail as a Local Anesthetic for Lumbar Decompression Surgery: A Single Institutional Experience.

OBJECTIVE: The goal of this study is to discuss our initial experience with a multimodal opioid-sparing cocktail containing ropivacaine, epinephrine, clonidine, and ketorolac (RECK) in the postoperative management of lumbar decompression surgeries. METHODS: Patients were either administered no local anesthetic at the incision site or were administered a weight-based amount of RECK into the paraspinal musculature and subdermal space surrounding the operative site once the fascia was closed. We performed a retrospective chart review of all patients 18 years of age or older undergoing lumbar laminectomy and lumbar diskectomy surgeries between December 2019 and April 2021. Outcomes including total opioid use, measured as morphine milligram equivalent, length of stay, and postoperative visual analog scores for pain, were collected. Relationships between variables were analyzed with Student's t-test, chi-square tests, and Fisher exact tests. RESULTS: A total of 121 patients undergoing 52 lumbar laminectomy and 69 lumbar diskectomy surgeries were identified. For lumbar laminectomy, patients who were administered RECK had decreased opioid use in the postoperative period (11.47 ± 12.32 vs. 78.51 ± 106.10 morphine milligram equivalents, P = 0.019). For patients undergoing lumbar diskectomies, RECK administration led to a shorter length of stay (0.17 ± 0.51 vs. 0.79 ± 1.45 days, P = 0.019) and a lower 2-hour postoperative pain score (3.69 ± 2.56 vs. 5.41 ± 2.28, P = 0.006). CONCLUSIONS: The RECK cocktail has potential to be an effective therapeutic option for the postoperative management of lumbar decompression surgeries.

Evaluating a unique enhanced recovery protocol in laparoscopic donor nephrectomy: A single center experience.

INTRODUCTION: Enhanced recovery after surgery (ERAS) protocols have been associated with a reduction in opioid consumption and a hastening in recovery in abdominal surgery. However, their impact on laparoscopic donor nephrectomy (LDN) has not been fully elucidated. The aim of this study is to evaluate opioid consumption and other relevant outcome measures before and after implementation of a unique LDN ERAS protocol. METHODS: 244 LDN patients were included in this retrospective cohort study. Forty-six underwent LDN prior to implementation of ERAS, whereas 198 patients received ERAS perioperative care. The primary outcome was daily oral morphine equivalent (OME) consumption averaged over the entire postoperative stay. Due to removal of preoperative oral morphine from the protocol partway through the study period, the ERAS group was further subdivided into morphine recipients and non-recipients for subgroup analysis. Secondary outcomes included the incidence of postoperative nausea and vomiting (PONV), length of stay, pain scores, and other relevant measures. RESULTS: ERAS donors consumed significantly fewer average daily OMEs than Pre-ERAS donors (21.5 vs. 37.6, respectively; p < .0001). There were no statistically significant differences in OME consumption between morphine recipients and non-recipients. The ERAS group experienced less PONV (44.4% requiring one or more rescue antiemetic postoperatively, vs. 60.9% of Pre-ERAS donors; p = .008). CONCLUSIONS: A protocol pairing lidocaine and ketamine with a comprehensive approach to preoperative PO intake, premedication, intraoperative fluid management and postoperative pain control is associated with reduced opioid consumption in LDN.

Evidence for a Multimodal Pain Management Regimen in Reduction of Postoperative Opioid Use in Pediatric Patients Receiving Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: This project aims to evaluate the relationship between increased use of intraoperative nonopioid analgesics, muscle relaxers, and anesthetics and postoperative outcomes, including opioid utilization, time until ambulation, and hospital length of stay. SUMMARY OF BACKGROUND DATA: Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine that occurs in otherwise healthy adolescents, occurring with a frequency of 1% to 3%. Up to 60% of patients receiving spinal surgeries, particularly posterior spinal fusion (PSF), experience at least 1 day of moderate-to-severe pain after surgery. PATIENTS AND METHODS: This is a retrospective chart review of pediatric patients aged 10 to 17 having received PSF with >5 levels fused for AIS at a dedicated children's hospital and a regional tertiary referral center with a dedicated pediatric spine program between January 2018 and September 2022. A linear regression model was used to evaluate the influence of baseline characteristics and intraoperative medications on the total amount of postoperative morphine milligram equivalents received. RESULTS: There were no significant differences in the background characteristics of the two patient populations. Patients receiving PSF at the tertiary referral center received equivalent or greater amounts of all nonopioid pain medications and demonstrated decreased time until ambulation (19.3 vs . 22.3 h), postoperative opioid use (56.1 vs . 70.1 MME), and postoperative hospital length of stay (35.9 vs . 58.3 h). Hospital location was not individually associated with a difference in postoperative opioid use. There was not a significant difference in postoperative pain ratings. When accounting for all other variables, liposomal bupivacaine had the greatest contribution to the decrease in postoperative opioid use. CONCLUSION: Patients receiving greater amounts of nonopioid intraoperative medications utilized 20% fewer postoperative morphine milligram equivalents, were discharged 22.3 hours earlier and had earlier recorded evidence of mobility. Postoperatively, nonopioid analgesics were as effective as opioids in the reduction of subjective pain ratings. This study further demonstrates the efficacy of multimodal pain management regimens in pediatric patients receiving PSF for AIS.

Best Practice Alerts Informed by Inpatient Opioid Intake to Reduce Opioid Prescribing after Surgery (PRIOR): A Cluster Randomized Multiple Crossover Trial.

BACKGROUND: Overprescription of opioids after surgery remains common. Residual and unnecessarily prescribed opioids can provide a reservoir for nonmedical use. This study therefore tested the hypothesis that a decision-support tool embedded in electronic health records guides clinicians to prescribe fewer opioids at discharge after inpatient surgery. METHODS: This study included 21,689 surgical inpatient discharges in a cluster randomized multiple crossover trial from July 2020 to June 2021 in four Colorado hospitals. Hospital-level clusters were randomized to alternating 8-week periods during which an electronic decision-support tool recommended tailored discharge opioid prescriptions based on previous inpatient opioid intake. During active alert periods, the alert was displayed to clinicians when the proposed opioid prescription exceeded recommended amounts. No alerts were displayed during inactive periods. Carryover effects were mitigated by including 4-week washout periods. The primary outcome was oral morphine milligram equivalents prescribed at discharge. Secondary outcomes included combination opioid and nonopioid prescriptions and additional opioid prescriptions until day 28 after discharge. A vigorous state-wide opioid education and awareness campaign was in place during the trial. RESULTS: The total postdischarge opioid prescription was a median [quartile 1, quartile 3] of 75 [0, 225] oral morphine milligram equivalents among 11,003 patients discharged when the alerts were active and 100 [0, 225] morphine milligram equivalents in 10,686 patients when the alerts were inactive, with an estimated ratio of geometric means of 0.95 (95% CI, 0.80 to 1.13; P = 0.586). The alert was displayed in 28% (3,074 of 11,003) of the discharges during the active alert period. There was no relationship between the alert and prescribed opioid and nonopioid combination medications or additional opioid prescriptions written after discharge. CONCLUSIONS: A decision-support tool incorporated into electronic medical records did not reduce discharge opioid prescribing for postoperative patients in the context of vigorous opioid education and awareness efforts. Opioid prescribing alerts might yet be valuable in other contexts.(Anesthesiology 2023; 139:186-96).

Efficacy of an Opioid-Sparing Perioperative Multimodal Analgesia Protocol on Posterior Lumbar Fusion in a Hispanic Population: A Randomized Controlled Trial.

INTRODUCTION: Posterior lumbar fusion surgery has become more common amid an aging population, with degenerative disease as its most common indication. Historically, postoperative pain control for spine surgery has relied on opioids. However, opioid use is associated with adverse effects such as dependence, respiratory depression, and altered cognition. Our study aimed to determine whether an opioid-sparing multimodal analgesia regimen (ketorolac, orphenadrine, and gabapentin) could be a viable alternative to diminish opioid use compared with a standard opioid-based regimen in Hispanic patients undergoing posterior lumbar spinal fusion. METHODS: This was a randomized controlled trial of Hispanic patients scheduled to undergo elective posterior spinal fusion. Inclusion criteria included age 30 to 85 years, Hispanic ethnicity, lumbar stenosis between L1 and S1, elective posterior spinal fusion with instrumentation, American Society of Anesthesiologists Score <2, and consent to participate in the study. Patients were randomized into two groups, an experimental multimodal analgesia and control (opioid-based) treatment groups, and outcomes such as morphine milligram equivalents used, visual analog scale score, and length of hospital stay were compared between the groups. RESULTS: The MMA experimental group used significantly lower amounts of opioid (measured with morphine milligram equivalent) than the opioid-based group during the 12-hour and 24-hour postoperative periods ( P -value = 0.023 and P -value = 0.033, respectively). No statistically significant difference was observed in opioid use in the 48-hour postoperative period between both groups ( P -value = 0.066). The MMA group had significantly lower VAS scores reported at the 12-hour, 24-hour, and 48-hour postoperative periods compared with the opioid-based group ( P -values = 0.016, 0.020, and 0.020, respectively). No difference was observed in the length of hospital stay between groups ( P -value = 0.169). DISCUSSION: Implementing an MMA protocol in Hispanic patients undergoing posterior lumbar fusion resulted in decreased overall opioid use and decreased pain intensity compared with the opioid-based group. MMA is an effective alternative for pain control in patients who want to avoid opioid use. CLINICAL TRIAL REGISTRATION: Identifier: NCT05413902.