A randomized phase 2 study of the 5-HT4 receptor agonist felcisetrag for postoperative gastrointestinal dysfunction after bowel surgery.

BACKGROUND: Felcisetrag (5-hydroxytryptamine-4 receptor [5-HT4] agonist) is under investigation as prophylaxis or active treatment for accelerating resolution of gastrointestinal function post-surgery. METHODS: Phase 2, randomized, placebo-controlled, parallel five-arm, double-blind, multicenter study (NCT03827655) in 209 adults undergoing open or laparoscopic-assisted bowel surgery. Patients received intravenous placebo, felcisetrag 0.1 mg/100 â€‹mL or 0.5 mg/100 â€‹mL pre-surgery only, or pre-surgery and daily post-surgery until return of gastrointestinal function or for up to 10 days. PRIMARY ENDPOINT: time to recovery of gastrointestinal function. RESULTS: Median time to recovery of gastrointestinal function was 2.6 days for both felcisetrag 0.5 â€‹mg daily and 0.5 â€‹mg pre-surgery versus 1.9 days for placebo (p â€‹> â€‹0.05). There were no notable differences in adverse events between treatment arms. CONCLUSIONS: Felcisetrag was well tolerated with no new safety concerns. However, no clinically meaningful difference in time to recovery of gastrointestinal function versus placebo was observed. Further investigation of the utility of 5-HT4 agonists in complicated, open abdominal surgeries may be warranted.

Intraoperative Catastrophic Acute Pulmonary Embolism: A Case Report.

This case report describes a 75-year-old female with a medical history including recurrent bowel obstruction due to sigmoid stricture, atrial fibrillation managed with rivaroxaban, a 50-year one pack-per-day smoking history, hypertension, hyperlipidemia, peripheral vascular disease with bilateral iliac stents (2015), stage III chronic kidney disease, and renal artery stenosis with bilateral stenting. She was transferred from outside hospital for an elective sigmoidectomy with ileorectal anastomosis following several recent admissions due to bowel obstruction that had been managed non-operatively. She was deemed optimized for surgery by the primary care team; however, during induction, she developed pulseless ventricular tachycardia requiring extensive resuscitative efforts. Intraoperative findings revealed biventricular failure and a clot in the right pulmonary artery. Despite aggressive treatment, including veno-arterial extracorporeal membrane oxygenation (VA ECMO), the patient's condition deteriorated, and life support was ultimately withdrawn. This case highlights the challenges of managing complex surgical patients and underscores the importance of multidisciplinary care in such cases.

Reducing inpatient opioid consumption after caesarean delivery: effects of an opioid stewardship programme and racial impact in a community hospital.

Caesarean section is the most common inpatient surgery in the USA, with more than 1.1 million procedures in 2020. Similar to other surgical procedures, healthcare providers rely on opioids for postoperative pain management. However, current evidence shows that postpartum patients usually experience less pain due to pregnancy-related physiological changes. Owing to the current opioid crisis, public health agencies urge providers to provide rational opioid prescriptions. In addition, a personalised postoperative opioid prescription may benefit racial minorities since research shows that this population receives fewer opioids despite greater pain levels. Our project aimed to reduce inpatient opioid consumption after caesarean delivery within 6 months of the implementation of an opioid stewardship programme.A retrospective analysis of inpatient opioid consumption after caesarean delivery was conducted to determine the baseline, design the opioid stewardship programme and set goals. The plan-do-study-act method was used to implement the programme, and the results were analysed using a controlled interrupted time-series method.After implementing the opioid stewardship programme, we observed an average of 80% reduction (ratio of geometric means 0.2; 95% CI 0.2 to 0.3; p<0.001) in inpatient opioid consumption. The institution designated as control did not experience relevant changes in inpatient opioid prescriptions during the study period. In addition, the hospital where the programme was implemented was unable to reduce the difference in inpatient opioid demand between African Americans and Caucasians.Our project showed that an opioid stewardship programme for patients undergoing caesarean delivery can effectively reduce inpatient opioid use. PDSA, as a quality improvement method, is essential to address the problem, measure the results and adjust the programme to achieve goals.

Incidence and risk factors of chronic postoperative pain in same-day surgery: A prospective cohort study.

BACKGROUND: The amount of same-day surgery has increased markedly worldwide in recent decades, but there remains limited evidence on chronic postsurgical pain in this setting. METHODS: We assessed pain 90 days after ambulatory surgery in an international, multicentre prospective cohort study of patients ≥45 years old with comorbidities or ≥65 years old. Pain was assessed using the Brief Pain Inventory. Chronic postsurgical pain was defined as a change ≥1 in self-rated average pain at the surgical site between baseline and 90 days, and moderate to severe chronic postsurgical pain as a score ≥4 in self-rated average pain at the surgical site at 90 days. Risk factors for chronic postsurgical pain were identified using multivariable logistic regression. RESULTS: Between November 2021 and January 2023, a total of 2054 participants were included, and chronic postsurgical pain occurred in 12% of participants, of whom 93.1% had new chronic pain at the surgical site (i.e., participants without pain prior to surgery). Moderate to severe chronic postsurgical pain occurred in 9% of overall participants. Factors associated with chronic postsurgical pain were: active smoking (OR 1.82; 95% CI 1.20 to 2.76), orthopaedic surgery (OR 4.7; 95% CI 2.24 to 9.7), plastic surgery (OR 4.3; 95% CI 1.97 to 9.2), breast surgery (OR 2.74; 95% CI 1.29 to 5.8), vascular surgery (OR 2.71; 95% CI 1.09 to 6.7), and ethnicity (i.e., Hispanic/Latino ethnicity OR 3.41; 95% CI 1.68 to 6.9 and First Nations/Native persons OR 4.0; 95% CI 1.05 to 15.4). CONCLUSIONS: Persistent postsurgical pain after same-day surgery is common, usually moderate to severe in nature, and occurs mostly in patients without chronic pain prior to surgery.

Management of Acute Saddle Pulmonary Embolism in Pregnancy Following Fetal Surgery.

A 33-year-old gravidity three parity three (G3P3) woman at 34 weeks of pregnancy underwent fetal surgery to repair an open lumbosacral myelomeningocele at 22 weeks gestation and experienced preterm premature rupture of membranes as a result. She developed a saddle pulmonary embolus with signs of right heart strain while on prolonged bed rest. She was treated emergently with aspiration thrombectomy and suprarenal inferior vena cava (IVC) filter placement, followed by an uncomplicated cesarean delivery thereafter.

Aortic Regurgitation After Right Coronary Cusp Injury During Percutaneous Coronary Intervention.

Injury of a coronary cusp of the aortic valve is a rare complication that can occur during coronary angiography. It usually occurs from multiple attempts with different catheters to access the ostia of the right coronary artery, but it has also occurred accessing the ostia of the left coronary artery. We present the case of a patient who underwent coronary angiography with suspected coronary cusp injury that remained asymptomatic but was found to have severe aortic regurgitation during coronary artery bypass graft surgery (CABG) one week later, requiring an aortic valve replacement.

Virtual Reality Distraction for Reducing Acute Postoperative Pain After Hip Arthroplasty: A Randomized Trial.

BACKGROUND: Relaxation and distraction provided by virtual reality presentations might be analgesic and reduce the need for opioid analgesia. We tested the hypothesis that a virtual reality program (AppliedVR) decreases acute postoperative pain and opioid requirements in patients recovering from hip arthroplasty. We also evaluated whether virtual reality distraction improves patient mobility and reduces the need for antiemetics. METHODS: We evaluated 106 adults who were recovering from elective primary total hip arthroplasty. Participating patients were randomized to 2- to 8-minute-long 3-dimensional immersive virtual reality relaxation and distraction video presentations (eg, guided breathing exercises, games, mindfulness) or to 2-dimensional presentations of nature short films (eg, forest wildlife) with neutral music that was chosen to be neither overly relaxing nor distracting, presented through identical headsets. Our primary outcome was pain after virtual reality or sham video presentations, adjusted for pretreatment scores. Secondary outcomes included total opioid consumption, pain scores obtained per routine by nurse staff, perception of video system usability, and pain 1 week after hospital discharge. RESULTS: Fifty-two patients were randomized to virtual reality distraction and relaxation, and 54 were assigned to 2-dimensional sham presentations. Virtual reality presentations were not found to affect pain scores before and after presentations, with an estimated difference in means (virtual reality minus sham video) of -0.1 points (95% confidence interval [CI], -0.5 to 0.2; P = .391) on a 0 to 10 scale, with 10 being the worst. The mean (standard error [SE]) after-intervention pain score was estimated to be 3.4 (0.3) in the virtual reality group and 3.5 (0.2) in the reference group. Virtual reality treatment was not found to affect postoperative opioid consumption in morphine milligram equivalents, with an estimated ratio of geometric means (virtual reality/sham video) of 1.2 (95% CI, 0.6-2.1; P = .608). Virtual reality presentations were not found to reduce pain scores collected every 4 hours by nursing staff, with an estimated difference in means of 0.1 points (95% CI, -0.9 to 0.7; P = .768). CONCLUSIONS: We did not observe statistically significant or clinically meaningful reductions in average pain scores or opioid consumption. As used in our trial, virtual reality did not reduce acute postoperative pain.

Long-term Outcomes with Spinal versus General Anesthesia for Hip Fracture Surgery: A Randomized Trial.

BACKGROUND: The effects of spinal versus general anesthesia on long-term outcomes have not been well studied. This study tested the hypothesis that spinal anesthesia is associated with better long-term survival and functional recovery than general anesthesia. METHODS: A prespecified analysis was conducted of long-term outcomes of a completed randomized superiority trial that compared spinal anesthesia versus general anesthesia for hip fracture repair. Participants included previously ambulatory patients 50 yr of age or older at 46 U.S. and Canadian hospitals. Patients were randomized 1:1 to spinal or general anesthesia, stratified by sex, fracture type, and study site. Outcome assessors and investigators involved in the data analysis were masked to the treatment arm. Outcomes included survival at up to 365 days after randomization (primary); recovery of ambulation among 365-day survivors; and composite endpoints for death or new inability to ambulate and death or new nursing home residence at 365 days. Patients were included in the analysis as randomized. RESULTS: A total of 1,600 patients were enrolled between February 12, 2016, and February 18, 2021; 795 were assigned to spinal anesthesia, and 805 were assigned to general anesthesia. Among 1,599 patients who underwent surgery, vital status information at or beyond the final study interview (conducted at approximately 365 days after randomization) was available for 1,427 (89.2%). Survival did not differ by treatment arm; at 365 days after randomization, there were 98 deaths in patients assigned to spinal anesthesia versus 92 deaths in patients assigned to general anesthesia (hazard ratio, 1.08; 95% CI, 0.81 to 1.44, P = 0.59). Recovery of ambulation among patients who survived a year did not differ by type of anesthesia (adjusted odds ratio for spinal vs. general, 0.87; 95% CI, 0.67 to 1.14; P = 0.31). Other outcomes did not differ by treatment arm. CONCLUSIONS: Long-term outcomes were similar with spinal versus general anesthesia.

Implementing an Interdisciplinary Procedure Curriculum.

INTRODUCTION: This curriculum was designed to improve access to procedures for our internal medicine residents. METHODS: We created an interdisciplinary procedure course (IDPC) composed of two simulation sessions and a one-week procedural rotation supervised by multiple specialties including nephrology, cardiology, cardiothoracic anesthesiology, general anesthesiology, and interventional radiology. After the course, residents completed two surveys documenting the number of procedures and their level of confidence on a Likert scale (1 = very unconfident to 5 = very confident) prior to and after completing the curriculum. RESULTS: Sixteen residents participated in the course from September 2021 to June 2022. The collective number of procedures performed by these 16 residents increased from 176 to 343 after a one-week rotation. For arterial lines, the proportion of residents that reported an improvement in confidence scores was 0.44 (95% confidence interval 0.23 to 1, p-value of 0.60). The proportion of residents that had an increase in their confidence performing central lines was 0.63 (95% confidence interval 0.39 to 1, p-value of 0.23). For intubations, the proportion of residents that reported an improvement in confidence was 0.94 (95% confidence interval 0.72 to 1, p-value of 0.0006). CONCLUSION: By collaborating with multiple specialties, residents almost doubled the number of procedures performed during training and reported an increased level of confidence in procedural performance for airway intubation. We learned residents want to improve their access to procedures and described a curriculum that was easily implemented.

Incidence and risk factors for postoperative gastrointestinal dysfunction occurrence after gastrointestinal procedures in US patients.

BACKGROUND: Incidence of, and potential risk factors for, postoperative gastrointestinal dysfunction (POGD) after gastrointestinal procedures performed in US hospitals were examined. METHODS: This retrospective study used hospital discharge data of inpatients who underwent ≥1 gastrointestinal procedures from 1-Jan-2016 to 30-Apr-2019. POGD incidence was calculated based on all hospitalizations for MDC-06 procedures. Predictors of POGD were assessed using multivariable logistic regression. RESULTS: POGD incidence was 5.8% among 638 611 inpatient hospitalizations. Major bowel procedures, peritoneal adhesiolysis, and appendectomy were the most notable predictors of POGD among gastrointestinal procedures assessed (adjusted odds ratios [95% confidence intervals]: 2.71 [2.59-2.83], 2.48 [2.34-2.64], and 2.15 [2.03-2.27], respectively; all p < 0.05). Procedures performed by colorectal/gastroenterology specialists (0.86 [0.84-0.89]), and those performed percutaneously (0.55 [0.54-0.56]) were associated with significantly lower odds of POGD (both P < 0.05). CONCLUSIONS: Findings may help clinicians tailor management plans targeting patients at high-risk of POGD.

Outcomes with spinal versus general anesthesia for patients with and without preoperative cognitive impairment: Secondary analysis of a randomized clinical trial.

INTRODUCTION: The effect of spinal versus general anesthesia on the risk of postoperative delirium or other outcomes for patients with or without cognitive impairment (including dementia) is unknown. METHODS: Post hoc secondary analysis of a multicenter pragmatic trial comparing spinal versus general anesthesia for adults aged 50 years or older undergoing hip fracture surgery. RESULTS: Among patients randomized to spinal versus general anesthesia, new or worsened delirium occurred in 100/295 (33.9%) versus 107/283 (37.8%; odds ratio [OR] 0.85; 95% confidence interval [CI] 0.60 to 1.19) among persons with cognitive impairment and 70/432 (16.2%) versus 71/445 (16.0%) among persons without cognitive impairment (OR 1.02; 95% CI 0.71 to 1.47, p = 0.46 for interaction). Delirium severity, in-hospital complications, and 60-day functional recovery did not differ by anesthesia type in patients with or without cognitive impairment. DISCUSSION: Anesthesia type is not associated with differences in delirium and functional outcomes among persons with or without cognitive impairment.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

Pain, Analgesic Use, and Patient Satisfaction With Spinal Versus General Anesthesia for Hip Fracture Surgery : A Randomized Clinical Trial.

BACKGROUND: The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported. OBJECTIVE: To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia. DESIGN: Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505). SETTING: 46 U.S. and Canadian hospitals. PARTICIPANTS: Patients aged 50 years or older undergoing hip fracture surgery. INTERVENTION: Spinal or general anesthesia. MEASUREMENTS: Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care. RESULTS: A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups. LIMITATION: Missing outcome data and multiple outcomes assessed. CONCLUSION: Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.

Effects of Gabapentin Enacarbil on Postoperative Pain After Hip and Knee Arthroplasty: A Placebo-controlled Randomized Trial.

OBJECTIVES: Total joint arthroplasties are among the most common elective procedures performed in the United States, and they are associated with postoperative pain. Gabapentin enacarbil is a prodrug with an extended-release formulation that has been proposed for multimodal postoperative analgesia, but the drug's efficacy for major arthroplasties remains unclear. MATERIALS AND METHODS: We enrolled 60 adult patients scheduled for primary knee or hip arthroplasty expected to remain hospitalized for at least 3 days. Eligible patients were randomly assigned to placebo or gabapentin enacarbil 600 mg twice daily starting the day before surgery continuing for 3 days thereafter.The primary outcome was analyzed using a joint hypothesis framework of pain (0 to 10 verbal response scores) and cumulative opioid consumption (mg of morphine equivalent) within the first 72 hours. Secondary outcomes were nausea and vomiting, pain persisting 90 days after surgery, duration of hospitalization, and early postoperative health status using quality of recovery score (QoR-15). RESULTS: Twenty-eight patient in gabapentin enacarbil group and 32 in placebo group were analyzed. Since pain scores did not differ significantly (difference of means: -0.2 in pain scores; 95% confidence interval: -1.1, 0.7), nor did opioid consumption, conditions for joint hypothesis testing were not met. Moreover, there were no significant differences between groups for secondary outcomes. DISCUSSION: We did not identify statistically significant or clinically meaningful differences in our primary and secondary outcomes related to perioperative use of gabapentin enacarbil in patients having primary hip or knee arthroplasties.

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery.

BACKGROUND: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. METHODS: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. DISCUSSION: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

A multimodal approach to reducing post-caesarean opioid use: a quality improvement initiative.

OBJECTIVE: To evaluate the impact of a QI initiative to reduce post-caesarean opioid use. DESIGN: Retrospective cohort study. SETTING: Academic hospital in the USA. POPULATION: Women over 18 years undergoing caesarean section. METHODS: A quality improvement (QI) initiative titled Reduced Option for Opioid Therapy (ROOT) was implemented in women undergoing caesarean section. The intervention included implementation of a postpartum order set maximising the use of scheduled NSAIDs and acetaminophen. Additionally, nursing education promoted non-opioid therapy as first-line, with opioids reserved for breakthrough pain. Performance feedback was provided to nursing staff on a bimonthly basis. Post-caesarean opioid use was reviewed in the 6 months before and after implementation of ROOT. MAIN OUTCOME MEASURES: The primary outcome was the total morphine milligram equivalents (MME) consumed during the postpartum admission. Secondary outcomes included opioid use per postoperative day, the proportion of opioid-free admissions, the percentage of patients discharged with a prescription for opioids, prescription size, and pain scores. RESULTS: Following implementation of ROOT, median inpatient opioid use decreased by more than 60%, from 75 to 30 MME per admission (P < 0.001). The proportion of opioid-free admissions increased from 12.6% pre-intervention to 30.7% post-intervention (P < 0.001). Additionally, the median opioid dose prescribed at discharge decreased in the post-intervention cohort, and the proportion of patients discharged without an opioid prescription increased. The reduction in opioids was associated with a slight decrease in patient-reported pain scores. CONCLUSIONS: Implementation of ROOT significantly reduced opioid use while achieving comparable pain control. TWEETABLE ABSTRACT: Nursing education, and use of an order set prioritising non-opioid analgesics reduces post-caesarean opioid use.

Transversus abdominis plane block with liposomal bupivacaine versus continuous epidural analgesia for major abdominal surgery: The EXPLANE randomized trial.

OBJECTIVE: Compare transversus abdominis plane (TAP) blocks with liposomal bupivacaine were to epidural analgesia for pain at rest and opioid consumption in patients recovering from abdominal surgery. BACKGROUND: ERAS pathways suggest TAP blocks in preference to epidural analgesia for abdominal surgery. However, the relative efficacies of TAP blocks and epidural analgesia remains unknown. METHODS: Patients having major abdominal surgery were enrolled at six sites and randomly assigned 1:1 to thoracic epidural analgesia or bilateral/4-quadrant TAP blocks with liposomal bupivacaine. Intravenous opioids were used as needed. Non-inferiority margins were a priori set at 1 point on an 11-point pain numeric rating scale for pain at rest and at a 25% increase in postoperative opioid consumption. RESULTS: Enrollment was stopped per protocol at 3rd interim analysis after crossing an a priori futility boundary. 498 patients were analyzed (255 had TAP blocks and 243 had epidurals). Pain scores at rest in patients assigned to TAP blocks were significantly non-inferior to those given epidurals, with an estimated difference of 0.09 points (CI: -0.12, 0.30; noninferiority P < 0.001). Opioid consumption during the initial 3 postoperative days in TAP patients was not non-inferior to epidurals, with an estimated ratio of geometric means of 1.37 (CI: 1.05, 1.79; non-inferiority P = 0.754). However, the absolute difference was only 21 mg morphine equivalents over the 3 days. Patients with epidurals were more likely to experience mean arterial pressures <65 mmHg than those given TAP blocks: 48% versus 31%, P = 0.006. CONCLUSION: Pain scores at rest during the initial three days after major abdominal surgery were similar. Patients assigned to TAP blocks required more opioid then epidural patients but had less hypotension. Clinicians should reconsider epidural analgesia in patients at risk from hypotension. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02996227.

Complicated Neuraxial Anesthesia in a Patient With Tethered Spinal Cord.

Spinal anesthesia is a common anesthetic used in many surgical procedures. Anatomical variations and diseases make this procedure require extra considerations. Extra care should be taken into consideration in the pre-anesthesia evaluation when neuraxial anesthesia is planned. We present the case of a patient undergoing cesarean section for the arrest of labor, who had a complicated labor course due to unrecognized history of a tethered spinal cord leading to inadequate analgesia, requiring replacement of epidural analgesia and spinal anesthesia. Ultimately, the decision was made to proceed with general anesthesia due to the patient's discomfort. Exhaustive chart review after surgery showed a past MRI with evidence of a tethered spinal cord.

Spinal Anesthesia or General Anesthesia for Hip Surgery in Older Adults.

BACKGROUND: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied. METHODS: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 m) independently or with a walker or cane at 60 days after randomization. Secondary outcomes included death within 60 days, delirium, time to discharge, and ambulation at 60 days. RESULTS: A total of 1600 patients were enrolled; 795 were assigned to receive spinal anesthesia and 805 to receive general anesthesia. The mean age was 78 years, and 67.0% of the patients were women. A total of 666 patients (83.8%) assigned to spinal anesthesia and 769 patients (95.5%) assigned to general anesthesia received their assigned anesthesia. Among patients in the modified intention-to-treat population for whom data were available, the composite primary outcome occurred in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (relative risk, 1.03; 95% confidence interval [CI], 0.84 to 1.27; P = 0.83). An inability to walk independently at 60 days was reported in 104 of 684 patients (15.2%) and 101 of 702 patients (14.4%), respectively (relative risk, 1.06; 95% CI, 0.82 to 1.36), and death within 60 days occurred in 30 of 768 (3.9%) and 32 of 784 (4.1%), respectively (relative risk, 0.97; 95% CI, 0.59 to 1.57). Delirium occurred in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (relative risk, 1.04; 95% CI, 0.84 to 1.30). CONCLUSIONS: Spinal anesthesia for hip-fracture surgery in older adults was not superior to general anesthesia with respect to survival and recovery of ambulation at 60 days. The incidence of postoperative delirium was similar with the two types of anesthesia. (Funded by the Patient-Centered Outcomes Research Institute; REGAIN ClinicalTrials.gov number, NCT02507505.).

Oliceridine Exhibits Improved Tolerability Compared to Morphine at Equianalgesic Conditions: Exploratory Analysis from Two Phase 3 Randomized Placebo and Active Controlled Trials.

INTRODUCTION: In the management of postoperative acute moderate-to-severe pain, opioids remain an important component. However, conventional opioids have a narrow therapeutic index and are associated with dose-limiting opioid-related adverse events (ORAEs) that can result in worse patient outcomes. Oliceridine, a new intravenous µ-opioid receptor agonist, is shown in nonclinical studies to be biased for G protein signaling (achieving analgesia) with limited recruitment of ß-arrestin (associated with ORAEs). In two phase 3 randomized controlled studies of patients with moderate-to-severe acute pain following hard or soft tissue surgery, in which analgesia was measured using Sum of Pain Intensity Differences (SPID) from baseline over 48 and 24 h (SPID-48 and -24 respectively, oliceridine at demand doses of 0.1, 0.35, or 0.5 mg was highly effective compared to placebo, with a favorable safety profile compared to morphine. This exploratory analysis was conducted to determine whether the safety benefits seen with oliceridine persisted when adjusted for equal levels of analgesia compared to morphine. METHODS: Presence of at least one treatment-emergent ORAE (based on Medical Dictionary for Regulatory Activities [MedDRA]-coded events: hypoxemia, nausea, vomiting, sedation, pruritus, or dizziness) was used as the composite safety endpoint. A logistic regression model was utilized to compare oliceridine (pooled regimens) versus morphine, after controlling for analgesia (using SPID-48 or SPID-24 with pre-rescue scores carried forward 6 h). This analysis excluded patients receiving placebo and was repeated for each study and for pooled data. RESULTS: At a given level of SPID-48 or SPID-24, patients receiving oliceridine were less likely to experience the composite safety endpoint. Although not statistically significant at the 0.05 level in the soft tissue model, the odds ratio (OR) showed a consistent numerical trend for oliceridine, being approximately half that observed with morphine in both the hard (OR 0.499; 95% confidence interval [CI] 0.255, 0.976; p = 0.042) and soft (OR 0.542; 95% CI 0.250, 1.175; p = 0.121) tissue studies. Results from the pooled data were consistent with those observed in the individual studies (OR 0.507; 95% CI 0.304, 0.844; p = 0.009). CONCLUSION: Findings from this exploratory analysis suggest that at comparable levels of analgesia, patients receiving oliceridine were less likely to experience the composite safety endpoint consisting of ORAEs compared to patients treated with morphine. Oliceridine Exhibits Improved Tolerability Compared to Morphine at Equianalgesic Conditions: Exploratory Analysis from Two Phase 3 Randomized Placebo and Active Controlled Trials- A Video (MP4 99188 kb).