Impact of pharmacogenomic profiles on post-surgical pain following laparotomy for gynecologic pathology.

OBJECTIVES: The aim of this prospective study was to compare perioperative opioid use in women by status of CYP2D6, a highly polymorphic pharmacogene relevant to opioid metabolism. METHODS: Patients undergoing laparotomy were prospectively recruited and provided a preoperative saliva swab for a pharmacogenomic (PGx) gene panel. Postoperative opioid usage and pain scores were evaluated via chart review and a phone survey. Pharmacogenes known to be relevant to opioid metabolism were genotyped, and opioid metabolizing activity predicted by CYP2D6 genotyping. Patient and procedural factors were compared using Fisher's exact and Kruskal-Wallis tests. RESULTS: The 96 enrolled patients were classified as ultra-rapid (N = 3, 3%), normal (58, 60%), intermediate (27, 28%), and poor (8, 8%) opioid metabolizers. There was no difference in surgical complexity across CYP2D6 categories (p = 0.61). Morphine Milligram Equivalents (MME) consumed during the first 24 h after peri-operative suite exit were significantly different between groups: ultrarapid metabolizers had the highest median MME (75, IQR 45-88) compared to the other three groups (normal metabolizers 23 [8-45], intermediate metabolizers 48 [20-63], poor metabolizers 31 [12-53], p = 0.03). Opioid requirements were clinically greater in ultrarapid metabolizers during the second 24 h and last 24 h but were statistically similar (p = 0.07). There was no difference in MME prescribed at discharge (p = 0.22) or patient satisfaction with pain control (p = 0.64) between groups. CONCLUSIONS: A positive association existed between increased CYP2D6 activity and in-hospital opioid requirements, especially in the first 24 h after surgery. This provides important information to further individualize opioid prescriptions for patients undergoing laparotomy for gynecologic pathology.

Physical and psychological distress amongst patients undergoing neoadjuvant chemotherapy for advanced ovarian cancer.

OBJECTIVE: This study compares baseline clinical characteristics, physical function testing, and patient-reported outcomes for patients undergoing primary cytoreductive surgery versus neoadjuvant chemotherapy, with the goal of better understanding unique patient needs at diagnosis. METHODS: Patients with suspected advanced stage (IIIC/IV) epithelial ovarian cancer undergoing either primary cytoreductive surgery or neoadjuvant chemotherapy were enrolled in a single-institution, non-randomized prospective behavioral intervention trial of prehabilitation. Baseline clinical characteristics were abstracted. Physical function was evaluated using the Short Physical Performance Battery, Fried Frailty Index, gait speed, and grip strength. Patient-reported outcomes were evaluated using Patient-Reported Outcomes Measurement Information System metrics and the Perceived Stress Scale. RESULTS: There were no significant differences in demographics or clinical characteristics between cohorts at enrollment, with the exception of performance status, clinical stage, and albumin. While gait speed and grip strength were lower amongst neoadjuvant chemotherapy patients, there were no significant differences in physical function using the Short Physical Performance Battery and Fried Frailty Index. Patients in the neoadjuvant chemotherapy cohort reported decreased perception of physical function and increased fatigue on Patient-Reported Outcomes Measurement Information System metrics. A larger proportion of patients in the neoadjuvant cohort reported severe levels of emotional distress and anxiety, as well as greater perceived stress at diagnosis. CONCLUSIONS: Our findings suggest that patients undergoing neoadjuvant chemotherapy for advanced ovarian cancer present with increased psychosocial distress and decreased perception of physical function at diagnosis and may benefit most from early introduction of supportive care.

Defining optimal perioperative analgesia in patients undergoing laparotomy for advanced gynecologic malignancy: A randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways utilize multimodal analgesia. In pathways already utilizing incisional injection of liposomal bupivacaine (ILB), we assessed the benefit of adding intrathecal opioid analgesia (ITA). METHODS: In this randomized controlled non-inferiority trial in patients undergoing laparotomy for gynecologic malignancy, we allocated patients 1:1 to ILB alone versus ITA + ILB with 150 µg intrathecal hydromorphone. The primary endpoint was the Overall Benefit of Analgesia Score (OBAS) at 24 h following surgery. Secondary endpoints included pain scores, intravenous opioid use, and cost of care. RESULTS: Demographic and surgical factors were balanced for 105 patients. For the primary endpoint, ILB alone was non-inferior to ITA + ILB (median OBAS at 24 h of 4 vs 4; p = 0.70). We observed a significant reduction in the need for intravenous opioids (26% vs 71%; p < 0.001) and total opioid requirements (median 7.5 vs 39.3 mg morphine equivalents, p < 0.001) in the first 24 h. Clinically relevant improvements in pain scores were identified in the first 16 h after surgery favoring ITA + ILB. Total cost of the index episode, pharmacy costs, and costs at 30 days were not statistically different. CONCLUSIONS: Using OBAS as the primary endpoint, ILB alone was non-inferior to ITA + ILB. However, important cost-neutral benefits for ITA + ILB in the first 24 h post-operatively included lower pain scores and reduced need for intravenous opioids. These early, incremental benefits of adding ITA to ERAS bundles already utilizing ILB should be considered to optimize immediate post-operative pain.