September 2025

This is a randomized, double-blind, placebo-controlled clinical trial assessing the impact of ketamine on post-operative hospital length-of stay, total opioid consumption, incidence of post-operative ileus, and incidence of side-effects or adverse events in adult patients undergoing abdominal surgery following an existing ERAS protocol. The use of ketamine was not associated with a shorter hospital length of stay but was associated with a higher rate of adverse events including rapid responses and ICU transfers.  

Summary: This trial randomized 1,522 adult patients undergoing abdominal surgery following an ERAS protocol (not specified beyond “colorectal, ventral hernia, or surgical oncology ERAS protocols”) to receive either ketamine or normal saline via intravenous bolus at the time of anesthesia induction and continuing through 48 hours post-operatively. The primary outcome was hospital length-of-stay, while secondary outcomes included total opioid consumption and incidences of adverse events. Patients transferred directly from the operating room to the ICU still intubated and patients whose operation was aborted were excluded from all analysis. 

The median duration of hospital stay was five days in each group; authors state that regression analysis showed patients receiving ketamine to have an odds ratio of 1.21 for prolonged hospital stay, however the 95% confidence interval included 1.00 and is therefore not statistically significant (1.00—1.47). There was no difference in opioid consumption between ketamine and placebo groups. Patients in the ketamine group did experience higher odds of an ICU transfer, with an odds ratio of 2.03 (95% CI 1.14—3.63) and more often received antiemetics due to significant post-operative nausea and vomiting within 48 hours of surgery (55% versus 47%, p = 0.002). Randomization of patients to the ketamine group was not associated with lower odds of ileus requiring gastric decompression. Of note, the study drug was discontinued due to adverse effects in 32% of the ketamine group versus 13% of the placebo group, and all analysis was completed on an intention-to-treat basis. The high rate of drug discontinuation due to adverse effects, the limited patient population included, and its single center nature are the chief limitations of this trial.

Bottom line: Patients undergoing ERAS pathway abdominal operations randomized to ketamine versus placebo were more likely to experience post-operative ICU transfers and other adverse events, without evidence of shorter hospital stay or lower post-operative opioid consumption.

This retrospective study assessed surgical and oncologic outcomes of parenchymal-sparing hepatectomies (PSH) versus major hepatectomies (MH) for colorectal liver metastases. Among 206 patients who underwent curative-intent hepatectomy for ≥5 bilaterally distributed colorectal liver metastases at a single-institution, MHs were associated with increased estimated blood loss, length of stay, and rate of postoperative hepatic insufficiency, while PSHs had higher rates of R1 resection. There was no significant difference in overall survival or recurrence-free survival between the two groups. 

Summary: Colorectal liver metastases (CLMs) affect approximately one in four patients with colorectal cancer. Surgical resection is recognized as the gold standard treatment for CLMs, and is associated with a favorable (>50%) overall survival among well-selected patients, including those with bilateral CLMs. Nevertheless, there is not a clear consensus regarding the optimal surgical approach to CLM resection, as parenchymal-sparing hepatectomy (PSH) raises concern for margin status and local recurrence while major hepatectomies (MH) raise concern for major morbidity. This retrospective study aimed to evaluate the surgical and oncologic outcomes of R0-intent single-stage hepatectomies among patients with ≥5 bilaterally distributed CLMs to compare outcomes of PSHs versus MHs. 

Among 206 patients from 1998 to 2022, 90 (44%) underwent PSH, while 116 (56%) underwent MH. 59% of patients were male, and 98% received chemotherapy prior to hepatectomy. There were no significant differences between PSH and MH in major surgical complications (Clavien Dindo ≥ 3), reoperations within 45 days of surgery, and 90-day mortality. MH had significantly higher estimated blood loss (median 350 mL, IQR 250-575 versus 250 mL, IQR 158-400 for PSH; p=0.002), length of stay (median 6 days, IQR 5-8 versus 5 days, IQR 4-7 for PSH; p<0.001), and hepatic insufficiency (12.9% incidence vs 1.1% incidence; p=0.003), and significantly lower rates of R1 resection (30.2% versus 46.7%, p=0.020). Of note, there was no difference in rates of R1 resection between the two groups when stratifying by total number of tumors (p=0.165). 

With a median follow-up of 48.5 months, the median overall survival was 51.0 months (IQR 43.9-58.0) and recurrence-free survival was 8.2 months (IQR 7.1-9.3). 173 patients (84.0%) developed a recurrence, of which 106 (61%) were intrahepatic. Kaplan-Meier analyses found no significant difference between the two groups for overall survival (p=0.072) or recurrence-free survival (p=0.585). Additionally, there was no difference in hepatic-specific disease-free survival (median 11.6 months, IQR 7.9-15.3; p=0.320). Multivariate analysis found no association between resection type and overall survival. 

Study limitations included exclusion of patients who required combined ablation or extrahepatic resection, significant differences in length of follow-up between PSH (median 30.0 months, IQR 24.5-35.5) and MH (median 60.8, IQR 44.2-77.3), and variability in surgical practice – notably in minimally invasive surgery – over the two decades included in the study. Despite these limitations, this study provides compelling evidence to support the use of PSH among patients with bilateral colorectal liver metastases. 

Bottom line: This single-institution retrospective study of patients who underwent hepatic resection for ≥5 bilaterally distributed colorectal liver metastases found that parenchymal-sparing hepatectomy had similar short-term surgical outcomes and long-term oncologic outcomes when compared to major hepatectomy, despite higher rates of R1 resection, supporting the use of parenchymal-sparing hepatectomy as a surgical approach in these patients.

Synopsis: This retrospective cohort study utilizes the VA Million Veteran Program (MVP) and VA Surgical Quality Improvement Program (VASQIP) to examine the impact of drug-gene interactions on post-surgical outcomes in vascular surgery. Patients with two or more drug-gene interactions experienced longer hospital stays, higher 30-day readmission rates, and increased rates of the composite outcome of stroke, myocardial infarction, or myocardial injury after noncardiac surgery, underscoring the clinical relevance of pharmacogenetic interactions in adverse outcomes.

Summary: Adverse drug reactions, influenced by individual patient variations in drug metabolism, contribute to perioperative morbidity and mortality. Pharmacogenetic (PGx) information, which tailors medication based on a patient’s DNA profile, has been translated into clinical practice for many US FDA approved drugs and contributed to improved outcomes. However, the impact of PGx on vascular surgery patients, who are frequently prescribed drugs with known drug-gene interactions during the perioperative period, remains underexplored.

To address this, the study analyzed genetic data from the MVP and surgical outcomes from the VASQIP for veterans undergoing vascular procedures between January 2011 and December 2022. Patients with documented vascular surgeries and genetic data were included, with drug exposure assessed from 30 days before to 7 days after surgery. Outcomes evaluated included length of stay (LOS), 30-day readmission, a composite outcome (stroke, myocardial infarction, or myocardial injury after noncardiac surgery), and 30-day postoperative mortality. Statistical analyses used mean (SD) for continuous variables, logistic regression for binomial variables, and negative binomial regression for count variables, with all models adjusted for the same covariates.

The study included 10,098 veterans (mean [SD] age, 68.8 [8.3] years; 15.7% Black [self-reported]; 97.9% male) after excluding those with multiple procedures, long-term dialysis, missing baseline eGFR, or incomplete genetic data. Of these, 49.7% had drug-gene interactions, primarily involving proton pump inhibitors (associated gene: CYP2C19), statins (SLCO1B1), and clopidogrel (CYP2C19). For each drug studied, the authors identified patients in the cohort with phenotypes that were actionable: poor, intermediate, rapid, or ultrarapid metabolizers. Patients were stratified by the number of drug-gene interactions (0, 1, 2, or 3+). Compared to those with no interactions, patients with any drug-gene interactions had significantly longer LOS: 0 interactions, 3 (1–6) days; 1 interaction, 3 (1–7) days (P < .001); 2 interactions, 3 (1–7) days (P < .001); 3+ interactions, 4 (2–8) days (P < .001). Both 30-day readmission and composite outcome rates were significantly higher in patients with 2 or 3+ interactions: readmission rates were 17.4% (0 interactions), 17.6% (1 interaction, P = .84), 21.2% (2 interactions, P = .004), and 25.1% (3+ interactions, P < .001); composite outcome rates were 3.5% (0 interactions), 4.1% (1 interaction, P = .24), 5.7% (2 interactions, P = .001), and 5.5% (3+ interactions, P = .02).

Limitations of the study include the predominantly male cohort (97.9%), potential underreporting of events due to unavailable Medicare data, and the study’s focus on pharmacokinetic rather than pharmacodynamic responses or drug-drug interactions. Copy number variants were also not assessed.

Bottom Line: Drug-gene interactions in vascular surgery patients are associated with longer hospital stays, higher readmission rates, and increased cardiovascular morbidity.