The Association of Guideline-Directed Prophylaxis With Postoperative Nausea and Vomiting in Adult Patients: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Consensus guidelines for postoperative nausea and vomiting (PONV) prophylaxis recommend a risk-based approach in which the number of antiemetics administered is based on a preoperative estimate of PONV risk. These guidelines have been adapted by the Multicenter Perioperative Outcomes Group (MPOG) to serve as measures of clinician and hospital compliance with guideline-recommended care. However, the impact of this approach on clinical outcomes is not known. METHODS: We performed a single-center, retrospective study of adult patients undergoing general anesthesia from 2018 to 2021. Risk factors for PONV were defined using MPOG definitions: female sex, history of PONV or motion sickness, nonsmoker, inhaled anesthesia >60 minutes, high-risk procedure (cholecystectomy, laparoscopic, gynecologic), and age <50 years. Adequate prophylaxis was defined using the MPOG PONV-05 metric: at least 2 agents for patients with 1 to 2 risk factors and at least 3 agents for patients with 3+ risk factors. PONV was defined as documented PONV or receipt of rescue antiemetics. To estimate the association between adequate prophylaxis and PONV, we used Bayesian binomial models with overlap propensity score weighting. RESULTS: We included 76,703 cases (43% receiving adequate prophylaxis) with PONV occurring in 19%. In unadjusted and unweighted comparison, adequate prophylaxis was associated with increased incidence of PONV: median odds ratio 1.21 (95% credible interval [1.16-1.25]). However, after propensity score weighting and multivariable adjustment, adequate prophylaxis was associated with reduced relative and absolute risk for PONV: weighted marginal median odds ratio 0.90 [0.84-0.98] and absolute risk reduction (ARR) 1.6% [0.6%-2.6%]. There was evidence for a differential effect of adequate prophylaxis across the guideline-defined risk spectrum, with benefit seen in patients with 1 to 5 risk factors (conditional probabilities of benefit >0.81), but not in those at high predicted risk. Patient-specific, covariate-adjusted ARR was heterogeneous, with a median patient-specific conditional probability of benefit of 0.84 (95% credible interval, 0.73-0.90). CONCLUSIONS: Guideline-directed PONV prophylaxis is associated with a modest reduction in PONV, although this effect is small and heterogeneous on the absolute scale. We found evidence for a differential association between adequate prophylaxis and PONV across the guideline-defined risk spectrum, with diminution in patients at very high predicted preoperative risk. While patient-specific benefit was heterogenous, most patients had reasonably high predicted probabilities of absolute benefit from a guideline-directed strategy. Further assessment of these associations in a multicenter setting, with more robust investigation of risk prediction methods will allow for better understanding of the optimal approach to PONV prophylaxis.

Postoperative analgesic consumption for primary versus first repeat Cesarean delivery: a historical cohort study.

PURPOSE: It is unclear if postoperative pain experience and opioid consumption differ in patients undergoing primary vs repeat Cesarean delivery (CD) as prior studies have yielded conflicting results and none used the same patients as their own controls. We sought to compare opioid consumption and pain scores in patients undergoing both a primary and a first repeat CD, using the same patients as their own controls. METHODS: We conducted a single-centre historical cohort study of patients who underwent both a primary and a first repeat CD under neuraxial anesthesia between 1 January 2016 and 30 November 2022. The same standardized multimodal analgesic regimen was used for all patients. The primary outcome was opioid consumption in oral morphine equivalents (OME) at 48 hr after surgery. Secondary outcomes included area under the curve for pain scores at 24 and 48 hr, and opioid consumption at 24 hr. RESULTS: We included 409 patients. In unadjusted analysis, there were no significant differences between primary and repeat CD in median [interquartile range] opioid consumption at 48 hr (45 [15-89] mg vs 45 [15-83] mg OME) or in any of the secondary outcomes. In the multivariable model adjusting for age, body mass index, anxiety, depression, priority, surgery duration, gestational age, receipt of postoperative ketorolac, and neuraxial type, repeat CD was still not associated with increased opioid consumption compared with primary CD (adjusted rate ratio, 1.20; 95% confidence interval, 0.95 to 1.51). CONCLUSION: In this retrospective study, we found no differences in postoperative opioid consumption or reported pain scores in patients who underwent both a primary and a first repeat CD.

RéSUMé: OBJECTIF: Nous ne savons pas si l'expérience de la douleur postopératoire et la consommation d'opioïdes diffèrent chez la patientèle accouchant par césarienne pour la première fois ou pour la seconde fois. En effet, les études antérieures ont donné des résultats contradictoires et aucune n'a utilisé la même patientèle comme témoins. Nous avons cherché à comparer la consommation d'opioïdes et les scores de douleur chez les personnes parturientes exposées à la fois à un premier puis un deuxième accouchement par césarienne en recrutant les mêmes personnes en tant que leurs propres témoins. MéTHODE: Nous avons mené une étude de cohorte historique monocentrique auprès de personnes parturientes ayant subi à la fois une première et une seconde césarienne sous anesthésie neuraxiale entre le 1er janvier 2016 et le 30 novembre 2022. Le même régime analgésique multimodal standardisé a été utilisé pour toutes les personnes dans l'étude. Le critère d'évaluation principal était la consommation d'opioïdes en équivalents morphine oraux (EMO) 48 heures après la chirurgie. Les critères d'évaluation secondaires comprenaient la surface sous la courbe pour les scores de douleur à 24 et 48 heures, et la consommation d'opioïdes à 24 heures. RéSULTATS: Nous avons inclus 409 personnes. Dans l'analyse non ajustée, il n'y avait pas de différence significative entre le premier et le deuxième accouchement par césarienne en ce qui concerne la consommation médiane d'opioïdes [écart interquartile] à 48 heures (45 [15 à 89] mg vs 45 [15­83] mg EMO) ou dans l'un des critères d'évaluation secondaires. Dans le modèle multivarié ajusté en fonction de l'âge, l'indice de masse corporelle, l'anxiété, la dépression, la priorité, la durée de la chirurgie, l'âge gestationnel, l'administration de kétorolac postopératoire et le type d'anesthésie neuraxiale, une deuxième césarienne n'était toujours pas associée à une consommation accrue d'opioïdes par rapport à une première césarienne (rapport de taux ajusté, 1,20; intervalle de confiance à 95 %, 0,95 à 1,51). CONCLUSION: Dans cette étude rétrospective, nous n'avons trouvé aucune différence dans la consommation d'opioïdes postopératoires ou les scores de douleur rapportés chez la patientèle ayant accouché par césarienne pour la première ou pour la deuxième fois.

Degradation of Lung Protective Angiotensin Converting Enzyme-2 by Meconium in Human Alveolar Epithelial Cells: A Potential Pathogenic Mechanism in Meconium Aspiration Syndrome.

BACKGROUND: Pancreatic digestive enzymes present in meconium might be responsible for meconium-induced lung injury. The local Renin Angiotensin System plays an important role in lung injury and inflammation. Particularly, angiotensin converting enzyme-2 (ACE-2) has been identified as a protective lung enzyme against the insult. ACE-2 converts pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1-7. However, the effect of meconium on ACE-2 has never been studied before. OBJECTIVE: To study the effect of meconium on ACE-2, and whether inhibition of proteolytic enzymes present in the meconium reverses its effects on ACE-2. METHODS: Alveolar epithelial A549 cells were exposed to F-12 medium, 2.5% meconium, meconium + a protease inhibitor cocktail (PIc) and PIc alone for 16 h. At the end of incubation, apoptosis was measured with a nuclear fragmentation assay and cell lysates were collected for ACE-2 immunoblotting and enzyme activity. RESULTS: Meconium caused a fourfold increase in apoptotic nuclei (p < 0.001). The pro-apoptotic effect of meconium can be reversed by PIc. Meconium reduced ACE-2 enzyme activity by cleaving ACE-2 into a fragment detected at ~ 37 kDa by immunoblot. PIc prevented the degradation of ACE-2 and restored 50% of ACE-2 activity (p < 0.05). CONCLUSION: These data suggest that meconium causes degradation of lung protective ACE-2 by proteolytic enzymes present in meconium, since the effects of meconium can be reversed by PIc.