Prediction of postoperative nausea and vomiting by point-of-care gastric ultrasound: can we improve complications and length of stay in emergency surgery? A cohort study

Background Postoperative nausea and vomiting and postoperative ileus are common after major digestive surgery and represent one of the significant problems in Acute Care Surgery. The delivery model of emergency surgery needs to be improved in order to foster a patient-centered care. The multimodal approach suggested by Enhanced Recovery After Surgery (ERAS®) Guidelines is gaining widespread acceptance but is difficult to apply to emergency surgery. Ultrasound examination of the gastric antrum allows a reliable assessment of gastric contents and volume and might help contribute to improve perioperative care in the emergency setting. Methods Gastric ultrasound examinations were performed preoperatively and postoperatively on forty-one patients undergoing emergency abdominal surgery. Gastric cross-sectional area (CSA) was measured, in order to estimate the gastric volume. The data obtained were used to evaluate a possible relationship between delayed gastric emptying and postoperative adverse event. Results Gastric antrum detection rate varied from 31.8% in open up to 78.9% in laparoscopic surgeries (p = 0.003). Six patients experienced adverse outcomes, had an antiemetic therapy administered and/or a nasogastric tube inserted. Mean CSA was significantly higher in this group (12.95 cm2 vs 6.12 cm2; p = 0.040). Conclusions Sensitivity of gastric ultrasound varies depending on surgical technique. A dilated gastric antrum is significantly related to postoperative adverse outcomes and a careful ultrasound follow-up might help tailor postoperative nutrition and antiemetic therapy. In patients who experienced adverse events, antral CSA showed an average increase of more than 50% over a period of 72 h after surgery. A relative measure could be used to predict the risk of postoperative ileus. Overall, gastric ultrasound seems to be a promising diagnostic tool and a useful way to integrate ERAS® protocol in emergency abdominal surgery.

Olanzapine (5 mg) Plus Standard Triple Antiemetic Therapy for the Prevention of Multiple-Day Cisplatin Chemotherapy-Induced Nausea and Vomiting: A Prospective Randomized Controlled Study

Objective A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy. Methods Patients received 3-day cisplatin-based chemotherapy(25mg/m2/d) were given either 5mg olanzapine quadruple therapy (aprepitant, tropisetron, dexamethasone) or 5mg olanzapine-based triplet therapy. The primary end-point was the complete response(CR) in the overall phase(OP)(0-120h) between quadruple regimen group and triplet regimen group. The secondary end-points were the CR in the acute phase(AP)(0-24h), delayed phase(DP)(25-120h) between two groups. The first time of vomiting was also compared by Kaplan-Meier curves. The impact of chemotherapy induced nausea and vomiting(CINV) on the quality of life was assessed by the Functional Living Index-Emesis(FLIE). Aprepitant-related adverse effects (AEs) was also recorded. Results (1) The primary end-point CR during overall phase was 76.0% (45/59) vs 67.0% (41/61) between the quadruple regimen group and triplet regimen group(P =0.271). The secondary end-point CR during the AP was significantly higher in the quadruple group than in the triple group, which was 100.0%(59/59) vs 93.0%(57/61)(P=0.045). The difference between the groups was especially greater in the delayed phase(quadruple group 76.0% (45/59) vs triple group 67.0%(41/61)(P=0.271)). The rate of patients who achieved total protection in the overall phase was also larger in the quadruple group than in the triple group(28.8% (17/59) vs 23.0%(14/61)(P=0.463)). During the OP, the incidence of no vomiting in quadruple group and triple group was 93.2%(55/59) vs 80.3%(49/61)(P=0.038)respectively.(2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group than in the triple group(P=0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire >108, this study exhibited identical life quality in quadruple group and the triplet group.(3) The most common aprepitant- and olanzapine-related AEs included sedation, fatigue and constipation. The occurrences between two groups were identical. Conclusion It may been recommended that combined 5mg olanzapine with aprepitant, tropisetron, dexamethasone quadruple therapy for the prevention of multiple-day cisplatin induced nausea and vomiting due to the better CINV control rate and safety.

The Efficacy of Olanzapine-Contained Antiemetic Therapy for Breast Cancer Patients: A Systematic Review and Pooled Analysis

Purpose: As an antipsychotic agent that targets multiple neurotransmitter receptors, olanzapine has been added to antiemetic therapies. However, olanzapine is rarely used in the real-world antiemetic strategies for breast cancer patients who suffered chemotherapy-induced nausea and vomiting. Therefore, in this study, we comprehensively reviewed the antiemetic researches related to olanzapine and pooled analyzed the results from clinical studies to confirm the efficacy of olanzapine in preventing nausea and vomiting in breast cancer.Methods: PubMed, Web of Science, EMBASE, and Cochrane Central databases were searched from inception through April 19, 2021. Both prospective and retrospective studies were eligible. The primary outcomes were complete response (defined as no vomiting and no use of rescue medications) and no nausea rate.Results: Five studies were identified in the systematic review, four of which with 466 breast cancer patients were included in the pooled analysis. In the acute period (0-24 hours), the olanzapine group had significantly higher rates of complete response (71.3% vs 48.1%, odds ratio [OR]: 2.66, 95% confidence interval [CI] 1.39-5.11, p = 0.003) and no nausea (70.0% vs 43.0%, OR: 3.55, 95% CI 1.76-7.18, p = 0.04) than the placebo group. While in the delayed period, the olanzapine group was also superior to the placebo group in terms of the complete response (82.5% vs 63.3%, OR: 3.81, 95% CI 1.58-9.15, p = 0.003) and no nausea (66.3% vs 51.9%, OR: 2.08, 95% CI 1.03-4.21, p = 0.04) rates. During the overall period in prospective studies, the proportions of complete response (50.0% vs 34.2%, OR: 1.93, p = 0.04) and no nausea (51.3% vs 25.3%, OR: 3.40, p = 0.0006) in the olanzapine group were higher than those in the placebo group. Conclusion: Highly emetogenic chemotherapy breast patients could benefit from olanzapine-contained antiemetic therapy. Furthermore, since the cost is low, olanzapine is worth further clinical application and promotion.

Efficacy of olanzapine combined with the standard triplet antiemetic therapy for cisplatin-based chemotherapy: A sub-analysis of a randomized, double-blind, placebo-controlled trial (J-FORCE).

12098 Background: In a randomized, double-blind, placebo-controlled trial (J-FORCE), we previously reported the efficacy of olanzapine (OLZ) 5 mg plus triplet antiemetic therapy for cisplatin (CDDP)-based chemotherapy-induced nausea and vomiting (CINV) in the delayed phase (24–120 h after CDDP treatment). Here, we report the results of a pre-planned subgroup analysis of this trial (in which risk factors were used as the allocation factors). This analysis was designed to determine which patients benefit more from OLZ. Methods: Subgroup analysis was performed on complete response (CR: no emesis and no rescue medication) in the acute (within 24 h of CDDP treatment) and delayed phase and time to treatment failure (TTF: time from CDDP treatment to the first vomiting or use of rescue medication). Data from 705 patients in the efficacy analysis population (354 in the OLZ group and 351 in the placebo (PLA) group) were analyzed by sex (male/female), age (≥55 years/ < 55 years), and CDDP dose (≥70 mg/m2/ < 70 mg/m2). For CR, we calculated point estimates of differences between groups and 95% confidence intervals and performed a Mantel-Haenszel test. We used the Kaplan-Meier method for the analysis of TTF, and comparisons between groups were made using a log-rank test. Results: Delayed CR (OLZ versus PLA) and risk difference (RD) of delayed CR following OLZ treatment were significantly greater than following PLA in the following subgroups: male (83.1% versus 70.5%, RD 12.6%, p = 0.001), female (70.9% versus 56.4%, RD 14.5%, p = 0.021), age ≥55 years (78.7% versus 67.6%, RD 11.1%, p = 0.003), age < 55 years (81.0% versus 57.4%, RD 23.6%, p = 0.005), and CDDP ≥70 mg/m2 (78.8% versus 65.3%, RD 13.5%, p < 0.001). TTF of all subgroups (male/female, ≥55 years/ < 55 years, and ≥70 mg/m2/ < 70 mg/m2) was significantly longer in the OLZ group than in the PLA group (HR 0.493, p < 0.001; HR 0.612, p = 0.022; HR 0.586, p < 0.001; HR 0.401, p = 0.005; HR 0.546, p < 0.001; HR 0.543, p = 0.031, respectively). Conclusions: Our results suggest a benefit of OLZ 5 mg plus triplet therapy regardless of risk factors for CDDP-based CINV. Clinical trial information: UMIN000024676. [Table: see text]

Cost-utility analysis of olanzapine in four-drug antiemetic therapy in Japanese patients treated with highly emetogenic cisplatin-containing chemotherapy

Purpose Olanzapine has been shown to have an additive effect on the three-drug antiemetic therapy, consisting of aprepitant, palonosetron, and dexamethasone, in a highly emetogenic cisplatin-containing chemotherapy. Although olanzapine may be more economical than aprepitant or palonosetron, an adequate cost-efficacy analysis has not been conducted. We conducted a cost-utility analysis to evaluate the cost-effectiveness of olanzapine in four-drug antiemetic therapy among Japanese patients.Methods We simulated model patients treated with highly emetogenic cisplatin-containing chemotherapy and developed a decision-analytical model of patients receiving triple antiemetic therapy with or without olanzapine. The cost, probabilities, and incremental cost-effectiveness ratio (ICER) of each treatment were calculated from the perspective of the Japanese healthcare payer. The threshold ICER was set at 45,867 United States dollars (USD) (5 million Japanese yen) per quality-adjusted life-year (QALY). The probabilities, utility value, and other costs were obtained from published sources. The robustness of this model was validated by one-way sensitivity analysis and probabilistic sensitivity analysis.Results The calculated ICER was 5,156 USD/QALY, which was below the threshold. Under the set conditions, the probabilistic sensitivity analysis revealed a 100% probability that olanzapine was cost-effective. Based on the one-way sensitivity analysis, reducing the cost of olanzapine below 10.78 USD placed the ICER below the threshold. Conclusion Olanzapine was cost-effective in the four-drug antiemetic therapy for Japanese patients treated with highly emetogenic cisplatin-containing chemotherapy

A phase II study of the safety of olanzapine for oxaliplatin based chemotherapy in coloraectal patients

Olanzapine has exhibited efficacy as an antiemetic agent when used with 5-HT3 receptor antagonists, dexamethasone, and NK1 receptor antagonists for patients receiving highly emetogenic chemotherapy. In addition, several studies have reported the efficacy or safety of olanzapine in patients receiving moderately emetogenic chemotherapy, including carboplatin, irinotecan, and oxaliplatin. However, no reports of olanzapine use have focused on patients receiving oxaliplatin-based chemotherapy. Therefore, we analyzed the safety of antiemetic therapy using olanzapine, palonosetron, aprepitant, and dexamethasone in colorectal cancer patients undergoing oxaliplatin-based chemotherapy. This study was a prospective phase II single-institution study of 40 patients (median age 60 years, 23 patients were male). The primary endpoint was the incidence of adverse events, and the exploratory endpoints were the rate of chemotherapy-induced nausea and vomiting. Almost all patients (90%) had a performance status of 0. All patients received the scheduled antiemetic therapy. The most common adverse event was somnolence (n = 7 patients, 17.5%). All adverse events were grade 1. Thirty-six patients were included in the exploratory analysis of efficacy. No patients experienced vomiting during the first 120 h after chemotherapy, and complete response and complete control were both 86.1%. The rate of total control was 55.6% during the same time period. Olanzapine use with 5-HT3 receptor antagonists, dexamethasone, and NK1 receptor antagonists was safe for colorectal cancer patients receiving oxaliplatin-based chemotherapy.