Sex Differences in Opioid Administration After Cardiac Surgery.

OBJECTIVES: To assess whether there are sex-based differences in the administration of opioid analgesic drugs among inpatients after cardiac surgery. DESIGN: A retrospective cohort study. SETTING: At a tertiary academic referral center. PARTICIPANTS: Adult patients who underwent cardiac surgery from 2014 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the cumulative oral morphine equivalent dose (OMED) for the postoperative admission. Secondary outcomes were the daily difference in OMED and the administration of nonopioid analgesics. The authors developed multivariate regression models controlling for known confounders, including weight and length of stay. A total of 3,822 patients (1,032 women and 2,790 men) were included. The mean cumulative OMED was 139 mg for women and 180 mg for men, and this difference remained significant after adjustment for confounders (adjusted mean difference [aMD], -33.21 mg; 95% CI, -47.05 to -19.36 mg; p < 0.001). The cumulative OMED was significantly lower in female patients on postoperative days 1 to 5, with the greatest disparity observed on day 5 (aMD, -89.83 mg; 95% CI, -155.9 to -23.80 mg; p = 0.009). By contrast, women were more likely to receive a gabapentinoid (odds ratio, 1.91; 95% CI, 1.42-2.58; p < 0.001). The authors found no association between patient sex and the administration of other nonopioid analgesics or specific types of opioid analgesics. The authors found no association between patient sex and pain scores recorded within the first 48 hours after extubation, or the number of opioids administered in close proximity to pain assessments. CONCLUSIONS: Female sex was associated with significantly lower amounts of opioids administered after cardiac surgery.

CPL-01, an investigational long-acting ropivacaine, demonstrates safety and efficacy in open inguinal hernia repair.

BACKGROUND: There is an unmet medical need for effective nonopioid analgesics that can decrease pain while reducing systemic opioid use. CPL-01, an extended-release injectable formulation of ropivacaine, is designed to safely provide analgesia and reduce or eliminate opioid use in the postoperative period. METHODS: Subjects undergoing open inguinal hernia with mesh were prospectively randomized to 1 of 3 doses of CPL-01 (10, 20, or 30 ml of 2% CPL-01, n = 14, 12, and 14, respectively), Naropin (150 mg, n = 40), or saline placebo (n = 13) infiltrated into the surgical site prior to closure. Pain and rescue medication usage was assessed, and Numeric Rating Scale (NRS) pain scores were adjusted for opioid usage using windowed worst observation carried forward (wWOCF) imputation. The primary efficacy endpoint was the mean area under the curve (AUC) of the NRS pain intensity scores with activity. RESULTS: Ninety-three subjects were treated, and 91 subjects completed 72 h of post-operative monitoring. Subjects who received the highest dose of CPL-01 in Cohort 3 showed a clinically meaningful reduction in postoperative pain intensity scores, which was the lowest value for any treatment in all cohorts, showing a trend towards statistical significance as compared to the pooled placebo group (p = 0.08), and numerically better than the 40 subjects who received Naropin. Opioid use through 72 h in subjects who received CPL-01 in Cohort 3 was approximately half of that shown in the placebo and Naropin groups; approximately 2/3 of the CPL-01 subjects (9/14) required no opioids at all through the first 72 h after the operation. More CPL-01 subjects avoided severe pain and were ready for discharge earlier than other groups. CPL-01 was safe and well-tolerated, with no clinically meaningful safety signals, and showed predictable and consistent extended-release pharmacokinetics. CONCLUSION: Results suggest that CPL-01 may be the first long-acting ropivacaine to address postoperative pain while reducing the need for opioids.

Lateness of Acetaminophen and Non-steroidal Anti-inflammatory Drug Administrations in a Retrospective Cohort of Medication Administration Records Among Patients After Cesarean Delivery.

INTRODUCTION: In an earlier study of patients after cesarean delivery, the concurrent versus alternating administration of acetaminophen and non-steroidal anti-inflammatory drugs was associated with a substantial reduction in total postoperative opioid use. This likely pharmacodynamic effect may differ if the times when nurses administer acetaminophen and non-steroidal anti-inflammatory drugs often differ substantively from when they are due. We examined the "lateness" of analgesic dose administration times, the positive difference if administered late, and the negative value if early. METHODS: The retrospective cohort study used all 67,900 medication administration records for scheduled (i.e., not "as needed") acetaminophen, ibuprofen, and ketorolac among all 3,163 cesarean delivery cases at the University of Iowa between January 2021 and December 2023. Barcode scanning at the patient's bedside was used right before each medication administration. RESULTS: There were 95% of doses administered over a 4.8-hour window, from 108 minutes early (97.5% one-sided upper confidence limit 105 minutes early) to 181 minutes late (97.5% one-sided lower limit 179 minutes late). Fewer than half of doses (46%, P <0.0001) were administered ±30 minutes of the due time. The intraclass correlation coefficient was approximately 0.11, showing that there were small systematic differences among patients. There likewise were small to no systematic differences in lateness based on concurrent administrations of acetaminophen and ibuprofen or ketorolac, time of the day that medications were due, weekday, year, or number of medications to be administered among all such patients within 15 minutes. DISCUSSION: Other hospitals should check the lateness of medication administration when that would change their ability to perform or apply the results of analgesic clinical trials (e.g., simultaneous versus alternating administration).

rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels.

Chronic pain is common and inadequately treated, making the development of safe and effective analgesics a high priority. Our previous data indicate that carbonic anhydrase-8 (CA8) expression in dorsal root ganglia (DRG) mediates analgesia via inhibition of neuronal ER inositol trisphosphate receptor-1 (ITPR1) via subsequent decrease in ER calcium release and reduction of cytoplasmic free calcium, essential to the regulation of neuronal excitability. This study tested the hypothesis that novel JDNI8 replication-defective herpes simplex-1 viral vectors (rdHSV) carrying a CA8 transgene (vHCA8) reduce primary afferent neuronal excitability. Whole-cell current clamp recordings in small DRG neurons showed that vHCA8 transduction caused prolongation of their afterhyperpolarization (AHP), an essential regulator of neuronal excitability. This AHP prolongation was completely reversed by the specific Kv7 channel inhibitor XE-991. Voltage clamp recordings indicate an effect via Kv7 channels in vHCA8-infected small DRG neurons. These data demonstrate for the first time that vHCA8 produces Kv7 channel activation, which decreases neuronal excitability in nociceptors. This suppression of excitability may translate in vivo as non-opioid dependent behavioral- or clinical analgesia, if proven behaviorally and clinically.

Analgésicos no opioides / Non-opioid analgesics

Resumen La analgesia multimodal es una recomendación universal para el control del dolor postoperatorio en situaciones clínicas diversas. Esta recomendación está avalada por la Sociedad Americana del Dolor (APS), la Sociedad Americana de Anestesia Regional y Medicina del Dolor (ASRA) y la Sociedad Americana de Anestesiólogos (ASA). La terapia analgésica multimodal se individualiza y ajusta de acuerdo con la edad, el tipo de dolor e intensidad, el procedimiento quirúrgico específico, las morbilidades asociadas y los efectos adversos de los fármacos. La escalera analgésica propuesta por la Organización Mundial de la Salud fue adaptada por la Federación Mundial de Sociedades y Asociaciones de Anestesiólogos (1997) para el abordaje del dolor agudo perioperatorio. Los analgésicos no opioides son la piedra angular para una terapia perioperatoria exitosa; entre los cuales se encuentran el paracetamol, los antiinflamatorios no esteroideos no selectivos y los COX-2, así como los coadyuvantes (para ver el artículo completo visite http://www.painoutmexico.com).

Abstract: Multimodal analgesia is an universal recommendation for the control of postoperative pain in diverse clinical situations. This recommendation is endorsed by the American Pain Society (APS), the American Society of Regional Anesthesia and Pain Medicine (ASRA) and the American Society of Anesthesiologists (ASA). Multimodal analgesic therapy is individualized and adjusted according to age, type of pain and intensity, specific surgical procedure, associated morbidities and adverse effects of drugs. The analgesic ladder proposed by the World Health Organization was adapted by the World Federation of Societies and Associations of Anesthesiologists (1997) for the management of acute perioperative pain. Non-opioid analgesics are the cornerstone for a successful perioperative therapy, among which are paracetamol, non-selective and COX-2, also include adjuvants (full version visithttp://www.painoutmexico.com ).