Evaluating tranexamic acid for the prevention and treatment of obstetric hemorrhage.

PURPOSE OF REVIEW: Tranexamic acid (TXA) has emerged as a promising pharmacological adjunct to treat and prevent postpartum hemorrhage (PPH). We provide an overview of TXA, including its pharmacology, key findings of randomized trials and observational studies, and critical patient safety information. RECENT FINDINGS: Pharmacokinetic data indicate that TXA infusions result in peak plasma concentration within 3 min (range: 1-6.6 min). Ex-vivo pharmacodynamic data suggest that low-dose TXA (5 mg/kg) inhibits maximum lysis for at least 1 h. In predominantly developing countries, TXA has demonstrated a 19% reduction in the risk of bleeding-related death among patients with PPH. Based on high-quality randomized trials, TXA prophylaxis does not effectively reduce the risk of PPH during vaginal delivery and is likely ineffective in reducing the PPH risk during cesarean delivery. TXA exposure does not increase the risk of maternal thrombotic events. Maternal deaths have occurred from accidental intrathecal TXA injection from look-alike medication errors. SUMMARY: TXA has shown promise as an important adjunct for PPH treatment, especially in low-resource settings. However, TXA is not recommended as PPH prophylaxis during vaginal or cesarean delivery. Patient safety initiatives should be prioritized to prevent maternal death from accidental intrathecal TXA injection.

A randomized controlled trial of spinal morphine with an enhanced recovery pathway and its effect on duration of analgesia after cesarean delivery.

BACKGROUND: Intrathecal morphine is frequently administered after cesarean delivery to provide pain relief lasting up to 24 h. An enhanced recovery after cesarean pathways reduces the amount of postoperative opioids needed. The ideal dose of intrathecal morphine when combined with a pathway has not been determined. METHODS: This was a non-inferiority trial in 72 healthy women undergoing a scheduled cesarean delivery. Women were randomized to receive either 50 mcg, 150 mcg, or 250 mcg of intrathecal morphine during spinal anesthesia, with a standardized postoperative enhanced recovery pathway. The time to request supplemental opioids was the primary outcome. Secondary outcomes included pain scores, side effects, and quality of recovery at 24 h. RESULTS: The duration of analgesia with 50 mcg of morphine (median 24.5 h [IQR: 3.5-34.4]) was inferior to 150 mcg (29.4 h [24.5-72]), and both doses were inferior to 250 mcg (32 h [30.5-72]). Women who received 50 mcg morphine had higher pain scores than the other doses, received more supplemental opioids, and had lower quality recovery scores. The secondary outcomes between 150 mcg and 250 mcg were similar. Side effects were similar among all groups. 63% of women who received 250 mcg remained opioid-free at 72 h, compared to 150 mcg (52%) and 50 mcg (30%). CONCLUSIONS: The duration of analgesia using intrathecal morphine with an enhanced recovery pathway was longer with 250 mcg than with lower doses, and side effects were similar. 50 mcg provided inferior pain relief over 24 h. More than half of our patients avoided additional opioids for up to 72 h with either 150 mcg or 250 mcg doses. REGISTRATION: Clinical trial number NCT05069012.

Phase II study of bemnifosbuvir in high-risk participants in a hospital setting with moderate COVID-19.

Background: Bemnifosbuvir, a novel, oral, nonmutagenic, nonteratogenic nucleotide analogue inhibits SARS-CoV-2 replication in vitro. Materials & methods: Adults in hospital settings with moderate COVID-19 were randomized 1:1 bemnifosbuvir/placebo. Study amended to two parts after interim analysis; part B enrollment limited owing to evolving standard of care. Results: Although the study ended early and did not meet the primary efficacy end point, bemnifosbuvir was well tolerated and did not contribute to all-cause mortality. Compared with placebo, bemnifosbuvir treatment resulted in 0.61 log10 greater viral load mean change on day 2; trend sustained through day 8. Treatment-emergent adverse events were similar in both groups; most were mild/moderate, unrelated to study drug. Conclusion: Our results suggest a potential role for bemnifosbuvir in blunting COVID-19 progression. Clinical Trial Registration: NCT04396106 (ClinicalTrials.gov).

Comparison of Opioid-Based Patient-Controlled Analgesia with Physician-Directed Analgesia in Acute Pancreatitis: A Retrospective Cohort Study.

BACKGROUND: Patient-controlled analgesia (PCA) is commonly used for acute postoperative pain management. Clinicians may also use PCA in the management of acute pancreatitis (AP); however, there is limited data on its impact on patient outcomes. We aimed to characterize a cohort of patients receiving PCA therapy for pain management in AP compared to those patients receiving standard physician-directed delivery of analgesia. METHODS: We conducted a retrospective cohort study of adult patients admitted with AP at a tertiary care center from 2008 to 2018. Exclusion criteria included patients with chronic opioid use, chronic pancreatitis and pancreatic cancer. Primary outcomes include length of stay (LOS) and time to enteral nutrition. Secondary outcomes include proportion of patients discharged with opioid and complications. Multivariate regression analysis and t-test were used for analysis. RESULTS: Among 656 AP patients who met the criteria, patients receiving PCA (n = 62) and standard delivery (n = 594) were similar in admission pain score, Charlson Comorbidity Index, and pancreatitis severity. There were significantly greater proportion of women, Caucasians and nonalcoholics who received PCA therapy (p < 0.01) than standard delivery. Multivariate regression analysis revealed that patients in the PCA group have a longer LOS (7.17 vs. 5.43 days, p < 0.007, OR 1.03; 95% CI 1.01-1.07), longer time to enteral nutrition (3.84 days vs. 2.56 days, p = 0.012, OR 1.11; 95% CI 1.02-1.20), and higher likelihood of being discharged with opioids (OR 1.94; 95% CI 1.07-3.63, p = 0.03). CONCLUSION: The use of PCA in AP may be associated with poorer outcomes including longer LOS, time to enteral intake and a higher likelihood of being discharged with opioids.

Estimating Obstetric Anaesthesia Workload: Number of Deliveries Compared to Time-Based Workload.

BACKGROUND: Number of deliveries is utilised to estimate obstetric anaesthesiologist workload; however, this may not reflect true workload. The goal of this analysis was to assess if including type of procedure, time required and length of each shift would better predict clinical workloads. METHODS: We queried the electronic medical records at a high volume, academic centre for 12 consecutive months of maternal deliveries. Data extracted included delivery type, analgesic/anaesthetic procedure and whether delivery occurred during weekday, weeknight or weekend shifts. To generate an hourly comparison of shifts of varying duration, procedures were divided by the number of hours per shift. To calculate obstetric anaesthesiology time-based workload, delivery type was multiplied by estimated time associated with the analgesic/anaesthetic procedure. RESULTS: A total of 4,598 deliveries occurred in the 12-month study period. The caesarean delivery rate was 32%, and labour epidural rate was 85%. 1,564 anaesthetic procedures occurred during weekdays and 2,557 occurred during the weeknights and weekends. After accounting for the duration of each procedure and hours per shift, mean 6 standard deviation time-based workload ratio was 0.68 6 0.12 on weekdays versus 0.36 6 0.07 on weeknights and weekends. CONCLUSION: Relative workload based on deliveries alone suggests 41% less workload during the weekday, whereas accounting for duration of each procedure and hours per shift resulted in an 89% greater workload on weekday shifts. The study highlights the importance of considering analgesic/anaesthetic procedures and estimates of time taken to perform them, not just number of deliveries when considering obstetric anaesthesiology workload.

Transnasal Humidified Rapid-Insufflation Ventilatory Exchange for Elective Laryngeal Surgery During Pregnancy: A Case Report.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) maintains oxygenation and blunts the partial pressure of carbon dioxide (PaCO2) rise in nonpregnant subjects during apnea. Physiologic changes of pregnancy may attenuate the utility of THRIVE. We present a nulliparous patient at 31 weeks' gestation undergoing tracheal dilation requiring general anesthesia without intubation utilizing THRIVE. Our data confirms prior reports in nonpregnant patients showing markedly extended time to desaturation. However, PaCO2 rise more closely mirrors classic apneic oxygenation in nonobstetric patients. The PaCO2 elevation and subsequent acidosis may limit the utility of THRIVE for prolonged apnea in pregnant surgical patients.

Preoperative Fasting Times for Patients Undergoing Caesarean Delivery: Before and After a Patient Educational Initiative.

OBJECTIVE: Prolonged preoperative fasting may lead to dehydration, hypoglycaemia, ketoacidosis and delayed recovery. We hypothesised that a patient educational initiative would decrease our preoperative fasting periods for elective caesarean delivery. METHODS: This was an observational quality improvement impact study. Elective caesarean patients who delivered during our study period were included in the study, 40 patients in the pre-intervention and 40 patients in the post-intervention groups. Only English-speaking patients were included. We developed a patient educational pamphlet outlining preoperative fasting and analgesic expectations for caesarean delivery that was given to every patient at her preoperative anaesthesia consultation. The pamphlet included the American Society of Anesthesiologists' preoperative fasting and enhanced recovery carbohydrate drink recommendations. The primary outcome measure was intended fasting duration for liquids (defined as time from last reported liquid consumption to scheduled caesarean delivery) before and after the patient educational initiative. Secondary outcomes included solid fasting time, types of liquids and solids consumed. RESULTS: The intended median (interquartile range) fasting time for liquids decreased from 10 (8.9-12) h to 3.5 (2.5-10) h (p<0.001). The fasting period for solids was not significantly different: 12.5 (10.5-14) h pre- versus 12.4 (10.6-14) h post-pamphlet introduction (p=0.384). Despite the recommendation, only 22.5% consumed a carbohydrate-containing drink with a modest decrease in water consumption (87.5% before and 67.5% after; p=0.009). CONCLUSION: A patient educational pamphlet significantly reduced fasting time for clear liquids. Future studies are needed to determine what barriers limited adherence to the recommended carbohydrate-containing drink consumption.

Society for Obstetric Anesthesia and Perinatology Consensus Statement: Monitoring Recommendations for Prevention and Detection of Respiratory Depression Associated With Administration of Neuraxial Morphine for Cesarean Delivery Analgesia.

The majority of women undergoing cesarean delivery in the United States receive neuraxial morphine, the most effective form of postoperative analgesia for this surgery. Current American Society of Anesthesiologists (ASA) and American Society of Regional Anesthesia and Pain Medicine (ASRA) recommend respiratory monitoring standards following neuraxial morphine administration in the general surgical population that may be too frequent and intensive when applied to the healthy obstetric population receiving a single dose of neuraxial morphine at the time of surgery. There is limited evidence to support or guide the optimal modality, frequency, and duration of respiratory monitoring in the postoperative cesarean delivery patient receiving a single dose of neuraxial morphine. Consistent with the mission of the Society for Obstetric Anesthesia and Perinatology (SOAP) to improve outcomes in pregnancy for women and neonates, the purpose of this consensus statement is to encourage the use of this highly effective analgesic technique while promoting safe practice and patient-centered care. The document aims to reduce unnecessary interruptions from respiratory monitoring in healthy mothers while focusing vigilance on monitoring in those women at highest risk for respiratory depression following neuraxial morphine administration. This consensus statement promotes the use of low-dose neuraxial morphine and multimodal analgesia after cesarean delivery, gives perspective on the safety of this analgesic technique in healthy women, and promotes patient risk stratification and perioperative risk assessment to determine and adjust the intensity, frequency, and duration of respiratory monitoring.

Impact of patient choice for different postcesarean delivery analgesic protocols on opioid consumption: a randomized prospective clinical trial.

BACKGROUND: Choice of postcesarean delivery analgesic protocol may improve pain experience and reduce analgesic requirements. METHODS: Cesarean delivery patients were randomly assigned either to choose their postcesarean delivery analgesia protocol or to have no choice and receive routine care. Choices were low (50 µg intrathecal morphine), medium (identical to routine care: 150 µg intrathecal morphine), or high (300 µg intrathecal morphine with 600 mg oral gabapentin). All groups received scheduled acetaminophen and ibuprofen. The primary outcome was oxycodone requirements 0-48 hours postdelivery in those offered versus not offered a choice. RESULTS: Of 160 women enrolled, 120 were offered a choice and 40 were not offered a choice. There was no difference in oxycodone requirements or pain associated with choice, but those who had a choice expressed more satisfaction than those who did not have a choice (mean (95% CI) difference 5% (0% to 10 %), p=0.005). In the choice group, the high dose group required more oxycodone (5 (0 to 15) mg 0-24 hours after delivery and 15 (10 to 25) mg at 24-48 hours; p=0.05 and p=0.001) versus the low and medium groups. The low dose group had less pruritus (p=0.001), while the high dose group had more vomiting (p=0.01) requiring antiemetic treatment (p=0.04). CONCLUSION: Having a choice compared with no choice routine care did not reduce oxycodone requirements or pain scores. However, women have insight into their analgesic needs; women offered a choice and who chose the higher dose analgesic protocol required more oxycodone, and women who chose the lower dose protocol required less oxycodone. Despite providing additional analgesic (six times more intrathecal morphine plus gabapentin in high dose vs low dose protocols), we still did not equalize postcesarean oxycodone requirement differences between groups. TRIAL REGISTRATION NUMBER: NCT02605187.

Use of Intravenous Acetaminophen in Postoperative Pain Management After Partial and Full Bony Impacted Third Molar Extractions: A Randomized Double-Blind Controlled Trial.

PURPOSE: Currently, there is a concern at the national level of the overuse of both prescription and nonprescription opioid use. The purpose of this study was to identify whether the use of the intravenous (IV) formulation of acetaminophen (Ofirmev; Mallinckrodt Pharmaceuticals, Staines-upon-Thames, United Kingdom) is an effective tool in the reduction of postoperative pain, with a secondary goal of reduction of postoperative narcotic use. MATERIALS AND METHODS: A total of 72 patients with previously diagnosed either partial bony or complete bony impacted third molars were selected with care to avoid long-acting local anesthetics or dissociative anesthetic agents. The patients' postoperative pain scores at 4 and 24 hours were collected via a verbal rating scale by the primary investigator. The exclusion criteria included administration of bupivacaine or ketamine, hepatic or renal impairment, pregnancy, or allergy to any of the normally administered sedation medications. RESULTS: At all postoperative increments (immediately, 4 hours, and 24 hours), there was no significant difference at P < .05 between scores for either the IV acetaminophen or placebo group. Although there was a recorded difference in reduction of pain at both 4 and 24 hours postoperatively, these were not statistically significant variables. CONCLUSIONS: The use of IV acetaminophen showed no statistically significant decrease in patient pain at either 4 or 24 hours postoperatively. Although there are not representative data suggesting the routine use of IV acetaminophen, on the basis of the abundance of literature on the treatment of pain for other procedures, this medication should not be discarded as ineffective.

Hemodynamic effects of once-daily tadalafil in men with signs and symptoms of benign prostatic hyperplasia on concomitant α1-adrenergic antagonist therapy: results of a multicenter randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the safety of daily coadministration of α-blockers with tadalafil 5 mg in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. The standard-of-care medical therapy for moderate to severe symptoms of benign prostatic hyperplasia is α(1)-adrenergic antagonist (α-blocker) therapy. METHODS: Men aged ≥ 45 years receiving stable α-blocker therapy were evaluated for eligibility before a 2-week single-blind, placebo lead-in period. Subsequently, 318 men were randomized to tadalafil 5 mg or placebo once daily for 12 weeks. Enrollment was monitored to ensure inclusion of men ≥ 75 years old and men taking nonuroselective α-blockers. The primary objective was to compare the proportion of men reporting treatment-emergent dizziness between the 2 treatment groups. Orthostatic vital signs, general safety, and the International Prostate Symptom Score were also assessed. RESULTS: The proportion of patients who reported treatment-emergent dizziness was not significantly different between the 2 treatment groups (tadalafil 7.0%; placebo 5.7%; P = .403). No difference between treatment groups was observed with respect to patients meeting the criteria for a positive orthostatic test (30 per treatment group, P = 1.00). The incidence of discontinuations was low among both treatment groups. CONCLUSION: Recognizing the limitations of the present study, the changes in the hemodynamic signs and symptoms were similar for the tadalafil and placebo groups in men with benign prostatic hyperplasia receiving concomitant α-blocker therapy. However, consistent with the results of previous clinical pharmacology studies of healthy subjects, a trend was seen for increased hemodynamic signs and symptoms in men taking nonuroselective α-blockers, most notably those taking doxazosin.