Safety and Pharmacogenetics of Oxycodone in Post-Cesarean Analgesia and Breastfeeding Dyads: A Proactive Approach to Precision Medicine.

Side effect profiles of different opioids in the perioperative setting: are they different and can we reduce them?

Intrathecal morphine (ITM) is frequently associated with side effects such as postoperative nausea and vomiting (PONV) and pruritus. The aim of this meta-analysis was to compare the impact of transversus abdominis plane (TAP) block versus ITM on side effects following cesarean delivery. PubMed, Embase, Web of Science, and CENTRAL were searched for randomized controlled trials that compared TAP with ITM for cesarean delivery. The primary outcomes were opioid-related side effects. The secondary outcomes included pain scores, opioid consumption, patient satisfaction, and time to the first analgesia request. Seven studies involving 660 patients were included. TAP blocks were performed with bupivacaine or ropivacaine. There was less PONV with TAP versus ITM (risk ratio [RR]=0.45, 95% confidence interval [CI]: 0.33-0.63, P<0.001; I2=0%), but no significant difference in pruritus (RR=0.76, 95% CI: 0.49-1.18, P=0.22; I2=78%) and sedation (RR=0.44, 95% CI: 0.19-1.00, P=0.05; I2=0%). TAP had a greater morphine consumption in 24 hours (mean difference: 5.80 mg; 95% CI: 1.38-10.22 mg, P=0.01; I2=89%) and higher pain score at rest at 6 hours (mean difference: 0.70, 95% CI: 0.39-1.02, P<0.001; I2=56%), but similar pain at rest at 24 hours and on movement compared with ITM. No differences were found in time to first analgesia and patient satisfaction. Compared with ITM, TAP block is associated with less PONV but inferior early analgesia after cesarean delivery. However, the heterogeneity among the studies highlights the need for more well-designed studies to obtain more robust conclusions.

ANESTHESIA has become remarkably safe, and while death and permanent damage have become rare occurrences, other sequelae of anesthesia are gaining more importance. Postoperative nausea and vomiting (PONV) still is the most troublesome adverse event encountered in the recovery room, despite advances in prevention and treatment. The incidence of PONV has remained high and has a major negative impact on patient satisfaction about the overall surgical experience. Furthermore, the ongoing trend toward ambulatory procedures has increased the focus on PONV as its occurrence may delay discharge or cause unanticipated hospital admission. General anesthesia has long been considered as causing a greater frequency and severity of PONV than regional anesthetic techniques. Recent studies investigating this time-honored dictum in a controlled manner mostly, but not unanimously, confirmed it. Accordingly, considerable effort has been invested to examine etiology, define patients at risk, and outline preventive and therapeutic strategies in patients undergoing general anesthesia. Reviews dealing with PONV have discussed almost exclusively general anesthesia and largely ignored regional anesthesia. This contrasts with the increasing popularity of regional anesthesia. A survey in Europe showed that one third of patients are undergoing regional anesthesia for their operative procedure. In France, the proportion of regional anesthesia increased from 15 to 25% of all anesthetics administered from 1980 to 1996. The number of local anesthetic and analgesic agents available for regional anesthesia has increased over the last two decades. Since the introduction of intrathecal and epidural morphine in 1979, a multitude of medications, such as synthetic opioids, 2-agonists, and cholinesterase inhibitors, have been introduced in an attempt to enhance the action of local anesthetics. The decision about their usefulness will not only rely on their effects on nerve blockade and pain relief, but also on their influence on side effects such as PONV. This review focuses on PONV in the setting of perioperative regional anesthesia. General aspects of PONV, such as physiology, patient, and perioperative factors involved are discussed. Few studies regarding these issues have been specifically devoted to regional anesthesia. Therefore, much information must be derived from investigations of general anesthesia. Specific regional anesthetic techniques and the influence of adjunctive medications on PONV are also presented. Combined general–regional anesthesia is purposefully excluded, avoiding the many variables introduced by general anesthesia. A final section is devoted to continuous peripheral nerve blocks and their possible impact on PONV.

Unpredictable interindividual variability in response to opioids results in inadequate analgesia and opioid-related adverse effects. The effects of the child's sex on opioid response have not been well studied. The aim of this study is to determine the effects of sex on opioid-related adverse effects in children undergoing tonsillectomy. Prospective observational clinical study. Outpatient pediatric surgery. Two hundred and seventy five children between 6 and 15 years of age undergoing outpatient tonsillectomy. All children received standard perioperative care with a standard intraoperative dose of morphine. Opioid-related analgesia and safety outcomes included incidences of respiratory depression (RD), postoperative nausea and vomiting (PONV) and incidence of prolonged stay in the, post-anesthesia recovery unit (PACU) due to opioid related adverse effects. Given the small sample of minority population, we focused our study on 219 white children. Significant morphine effect was observed in girls but not boys for PONV (P = 0.001) and prolonged PACU stay due to PONV (P = 0.010). Although the overall incidence of RD is not statistically different between boys and girls, the incidence of RD (52% vs 32%) and PONV (43% vs 4%) tended to be more in white girls than boys as the total perioperative morphine dose increased to 0.3 mg/kg or more. This study demonstrates that child's sex influences morphine's dose response and adverse effects. White girls have an unequal burden with higher incidences of PONV, RD, and prolonged PACU stays following tonsillectomy from PONV and RD as total morphine doses are increased.

Enhanced recovery after cesarean (ERAC) delivery is an evidence-based, multi-disciplinary approach throughout pre-, intra-, post-operative period. The ultimate goal of ERAC is to enhance recovery and improve the maternal and neonatal outcomes. This review highlights the role of anesthesiologist in ERAC protocols. This review provided a general introduction of ERAC including the purposes and the essential elements of ERAC protocols. The tool used for evaluating the quality of ERAC (ObsQoR-11) was discussed. The role of anesthesiologist in ERAC should cover the areas including management of peri-operative hypotension, prevention and treatment of intra- and post-operative nausea and vomiting, prevention of hypothermia and multi-modal peri-operative pain management, and active pre-operative management of unplanned conversion of labor analgesia to cesarean delivery anesthesia. Although some concerns still remain, ERAC implementation should not be delayed. Regular assessment and process improvement should be imbedded into the protocol. Further high-quality studies are warranted to demonstrate the effectiveness and efficacy of the ERAC protocol.

Background Lumbar fixation surgery is associated with moderate to severe postoperative pain. Methods A total of 68 patients of both sexes admitted for elective posterior stabilization for lumbar instability (ASA status I–II) were randomly allocated to receive either a 0.25% bupivacaine/fentanyl mixture (group BF, n =34) or placebo in the form of normal saline (group P, n =34) by a continuous infusion through a catheter placed subcutaneously at the end of surgery. The catheter was removed after 48 h postoperatively. Pain was assessed every 4 h after surgery using a visual analog scale. Opioid consumption, opioid-related side effects (postoperative nausea and vomiting, respiratory depression, or pruritus), wound-related complications (poor healing or infection), and patient satisfaction scores were compared in both groups. Results Bupivacaine/fentanyl wound infusion resulted in better analgesia and a significant decrease in opioid consumption. With respect to opioid-related and wound-related complications, there were no statistically significant differences between the two groups. The overall patient satisfaction was significantly higher in the BF group when compared with group P. Conclusion It was concluded that bupivacaine/fentanyl wound instillation improves pain control, decreases opioid requirements, and increases overall patient satisfaction.

Examining the Predictors of Postoperative Nausea and Vomiting in Women Following Cesarean Delivery

Opioid-induced respiratory depression (OIRD) and postoperative nausea and vomiting (PONV) are challenging, resource-intensive, and costly opioid-related adverse events (ORAEs). Utilizing the Premier Healthcare Database, we identified patients > 18 years old, who underwent at least one surgical procedure of interest (i.e., cardiothoracic/vascular, general/colorectal, obstetric/gynecologic, orthopedic, or urologic), and received at least one dose of intravenous morphine, hydromorphone, or fentanyl for acute postoperative pain. The incidence of OIRD and PONV using ICD-9 codes, factors influencing these AEs, length of stay (LOS) and related costs were analyzed. Among 592,127 inpatient stays, rates of respiratory depression ranged from 3% (obstetric/gynecologic) to 17% (cardiothoracic/vascular) and nausea/vomiting from 44% (obstetric/gynecologic) to 72% (general/colorectal). Increased odds of OIRD were associated with older age (cardiothoracic/vascular, general/colorectal, obstetric/gynecologic); obesity, respiratory conditions, and sleep apnea (all surgery groups); opioid dose (cardiothoracic/vascular, general/colorectal, orthopedic); and sedative use after day 1. Increased odds of PONV were associated with younger age, female sex, and major disease severity. When respiratory depression or nausea/vomiting was present versus absent, LOS was significantly longer, and hospital costs were higher. In this analysis, OIRD and PONV were more prevalent than previously reported, were associated with identifiable risk factors, and had substantial effects on resource utilization and costs.

Gabapentin and Post Tonsillectomy Pain-The Next Best Thing?

The efficacy of ginger for the prevention of postoperative nausea and vomiting: A meta-analysis

BackgroundLumbar spine surgery is associated with significant postoperative pain and a high incidence of postoperative nausea and vomiting (PONV). Inflammation is a known contributor to PONV risk, and the neutrophil-to-lymphocyte ratio (NLR) is a cost-effective parameter for evaluating systemic inflammation. Erector spinae plane block (ESPB) under ultrasound guidance is a regional anesthesia technique that may reduce postoperative pain, inflammatory responses, and opioid consumption. However, evidence on the relationship between preoperative NLR, PONV, and the effects of ESPB is limited.OverviewThis prospective, double-blind, single-center, parallel-group study will enroll 220 patients undergoing elective lumbar spine surgery under general anesthesia. Patients will be stratified by a preoperative NLR threshold of 2 into two equal groups and further randomized to receive either ultrasound-guided ESPB with ropivacaine or a saline control after anesthesia induction. All participants will receive standard PONV prophylaxis with intravenous ondansetron. Primary endpoints include the incidence of nausea, vomiting, and antiemetic requirements in the first and second 24-hour postoperative periods, as well as postoperative NLR. Secondary endpoints include pain scores, intraoperative anesthetic consumption, total postoperative analgesic use, time to first analgesic pump activation, patient satisfaction, recovery times, length of stay, opioid-related side effects, and serum neutrophil extracellular traps.ResultsAt the time of submission, the trial is ongoing and in the patient recruitment phase. No results are yet available.DiscussionThe study is designed to evaluate whether preoperative NLR can serve as a biomarker for PONV and to determine the effect of ESPB on NLR, PONV, and postoperative recovery parameters in lumbar spine surgery patients. The findings may provide evidence for individualized PONV prevention strategies and the perioperative application of ESPB.ConclusionThis trial will clarify the predictive value of NLR for PONV and assess the efficacy of ESPB in modulating postoperative inflammation and improving recovery in lumbar spine surgery.Clinical trial registrationClinicalTrials.gov identifier, NCT06127966.

Patients who undergo laparoscopic bariatric surgery (LBS) are susceptible to postoperative nausea and vomiting (PONV). Opioid-free anesthesia (OFA) or opioid-sparing anesthesia (OSA) protocols have been proposed as solutions; however, differences between the 2 alternative opioid protocols for anesthesia maintenance in obese patients remain uncertain. A network meta-analysis was conducted to compare the impacts of OFA and OSA on PONV. Systematic searches were conducted using Embase, PubMed, MEDLINE, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing OFA and OSA strategies. After screening according to the inclusion and exclusion criteria, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the credibility of the evidence. The main concern of this review was the difference between OFA and OSA in reducing PONV. The primary outcome was any PONV occurrence within 24 hours. Secondary outcomes included postoperative pain intensity, opioid consumption, opioid-related adverse events, and length of hospital stay. Fifteen RCTs involving 1310 patients were identified for a network meta-analysis from 1776 articles that compared OFA, OSA, and traditional opioid-based anesthesia (OBA) strategies in LBS. Twelve RCTs (80%) with 922 participants (70%) were eligible for the occurrence of PONV. These included 199 (22%) patients who received OFA and 476 (52%) and 247 (27%) patients who received OSA and OBA, respectively. OFA was more effective at reducing PONV (relative risks [RR], 0.6, 95% confidence interval [CI], 0.5-0.9, moderate-quality evidence) compared to OSA. No differences were observed in postoperative pain control or opioid consumption between the OFA and OSA strategies (very low-to high-quality evidence). Notably, OFA is associated with a higher risk of bradycardia than OSA (RR, 2.6, 95% CI, 1.2-5.9, moderate-quality evidence). OFA is more effective than OSA in reducing the occurrence of PONV during the early postoperative period of LBS, although it may associate with an increased risk of bradycardia. Patients who received either opioid-alternative strategy demonstrated similar effects in reducing postoperative opioid consumption and alleviating pain intensity.

Spinal anesthesia is the preferred anesthetic technique for cesarean deliveries. Postoperative nausea and vomiting (PONV) and pruritus occur in up to 80% and 83% of patients, respectively, after cesarean delivery with intrathecal opioids. Ondansetron is the recommended medication for PONV prophylaxis, but palonosetron, a second-generation 5-HT3 receptor antagonist, has a higher receptor affinity and a longer half-life. However, studies on palonosetron use in cesarean deliveries are limited. This study aimed to determine whether palonosetron was more effective than ondansetron in preventing intrathecal morphine-induced PONV and pruritus in cesarean deliveries. Parturients who underwent cesarean delivery under spinal anesthesia were randomized into 3 groups: P (palonosetron 0.075 mg), O (ondansetron 4 mg), and N (normal saline). The study drug was intravenously administered after the umbilical cord was clamped. The primary outcome measures were the 48-hour incidence of PONV and pruritus. The secondary outcome measures were the PONV and pruritus scores at the postanesthesia care unit (PACU) and ward, rescue medications, satisfaction scores, and adverse events. Ordinal data were analyzed using the Kruskal-Wallis test. Continuous and categorical data were analyzed using a 1-way analysis of variance, Kruskal-Wallis test, and Pearson's χ 2 test, respectively. A value of P < .05 was considered significant. Post hoc analysis pairwise comparisons with Bonferroni correction were also performed. Overall, 300 parturients were enrolled, and 297 parturients completed the study. One patient in the P group and 2 in the O group were excluded because of conversion to general anesthesia after failed spinal anesthesia. The baseline patient characteristics were comparable between the groups. The PONV incidence rates in the P, O, and N groups were 26.3% (95% confidence interval [CI], 17.4-35.1), 34.7% (95% CI, 25.1-44.3), and 50.0% (95% CI, 40.0-59.9), respectively ( P = .002). The incidence rates of pruritus in the P, O, and N groups were 69.7% (95% CI, 60.5-78.9), 76.5% (95% CI, 67.9-85.1), and 87.0% (95% CI, 80.3-93.7), respectively ( P = .013). Pairwise comparisons revealed significantly lower incidences of PONV and pruritus in the P group than in the N group ( P < .001 and P = .003, respectively). However, no significant differences were observed between the P and O groups or between the O and N groups. Additionally, the P group required significantly less nalbuphine rescue for pruritus than the N group ( P = .004 and P = .005 for the PACU and ward, respectively). PONV rescue, satisfaction scores, and adverse events were not significantly different among the 3 groups. Palonosetron effectively prevents intrathecal morphine-induced PONV and pruritus during cesarean delivery. However, the efficacy of palonosetron is not significantly different from that of ondansetron.

Postoperative nausea and vomiting (PONV) is the one of the most distressing problems associated with anesthesia and surgery. It may be cause dehydration, electrolyte imbalance, tension on the surgical repair site, venous hypertension and increased perception of pain, and may be especially harmful after neurosurgery or orthognathic surgery [1]. Many patients state that PONV is a more undesirable postoperative outcome than incisional pain [2]. PONV prophylaxis should be considered for patients at moderate to high risk for PONV, and antiemetic combination therapy or a multimodal approach are recommended for patients at high risk for PONV [3,4]. The concept of an antiemetic combination therapy was first introduced in 1988 by Parikh et al. [5] for chemotherapy induced vomiting. Prophylaxis with antiemetic drugs is the current gold standard for managing PONV. However, there is no completely effective pharmacologic agent for the prevention of PONV, and the potential adverse effects of antiemetic agents should not be overlooked. Nonpharmacologic methods such as acupuncture may also be used to as alternative or adjunct therapies to manage PONV. Dundee et al. [6] introduced the use of acupuncture as an antiemetic to manage PONV to the West in 1986. Although there was some debate over its effectiveness, many clinical studies were performed. A Cohrane review of 40 trials involving 4858 participants showed that P6 acupoint stimulation significantly reduced the incidence of PONV and the need for rescue antiemetics compared with sham treatment [7]. There are various methods of acustimulation in the prevention of PONV, such as manual [6] or electrical [8,9] stimulation. It is reported that prevention of PONV by electrical acustimulation is a cheap and simple technique comparable to ondansetron during and after cesarean delivery under spinal anesthesia [8]. An alternative method to acupoint stimulation using a capsicum component has also been developed. Several studies have shown that the application of medical and pharmaceutical products containing capsicum component (e.g., capsicum plaster or ointment) at acupoints reduced the incidence of PONV [10-13]. Capsicum plaster at either the Korean hand acupuncture point K-D2 or the Pericardium 6 acupoint reduced PONV in patients undergoing abdominal hysterectomy [11]. Capsicum plaster at Hegu acupoints reduced the incidence of PONV and also conferred a postoperative analgesic effect after orthognathic surgery [12]. Also, the incidence of PONV and rescue anti-emetic requirement following laparoscopic cholecystectomy were reduced in patients who had capsaicin ointment applied to the K-D2 point [13]. In this issue of the Korean Journal of Anesthesiology [14], the authors found that applying capsicum plaster at the P6 or K-D2 acupoints more effectively lowered the incidence of PONV and the severity of nausea and improved satisfaction during the 24-hr period after thyroid surgery, as compared to the control and sham groups. The incidence of nausea and vomiting during the 24 hr after surgery was 24% and 4%, 22% and 6%, 59% and 30%, and 50% and 24% in the P6, K-D2, control, and sham groups, respectively. Although the sample size of this study was not sufficiently large, it was calculated by a power analysis and the factors affecting PONV were comparable among the groups. Several clinical studies have shown that pharmacologic and nonpharmacologic combination therapies more effectively prevent PONV than pharmacologic therapy alone [9,10]. The combination of capsicum plaster at the Korean hand acupuncture points K-D2 with prophylactic ramosetron more effectively reduced the PONV compared with ramosetron alone in patients at high risk for PONV undergoing gynecologic laparoscopic surgery [10]. It is reported that perioperative P6 acustimulation with transcutaneous electrical acupoint stimulation may be an effective adjunct to the standard antiemetic drug therapy with ondansetron and dexamethasone to prevent PONV in patients undergoing infratentorial craniotomy [9]. The incidence of PONV is still high in some patients. Acupuncture and related therapies may be used as inexpensive and effective alternative or adjunct therapies along with standard antiemetic therapy for preventing PONV. Further studies are required to identify the optimal timing and effective method of acustimulation and combination with pharmacologic antiemetic therapies.

The changing role of monitored anesthesia care in the ambulatory setting.