Given the basic need for opioids in the perioperative setting, we investigated associations between opioid prescription levels and postoperative outcomes using population-based data of orthopedic surgery patients. We hypothesized that increased opioid amounts would be associated with higher risk for postoperative complications. Data were extracted from the national Premier Perspective database (2006-2013); N = 1,035,578 lower joint arthroplasties and N = 220,953 spine fusions. Multilevel multivariable logistic regression models measured associations between opioid dose prescription and postoperative outcomes, studied by quartile of dispensed opioid dose. Compared to the lowest quartile of opioid dosing, high opioid prescription was associated with significantly increased odds for deep venous thrombosis and postoperative infections by approx. 50%, while odds were increased by 23% for urinary and more than 15% for gastrointestinal and respiratory complications (P < 0.001 respectively). Furthermore, higher opioid prescription was associated with a significant increase in length of stay (LOS) and cost by 12% and 6%, P < 0.001 respectively. Cerebrovascular complications risk was decreased by 25% with higher opioid dose (P = 0.004), while odds for myocardial infarction remained unaltered. In spine cases, opioid prescription was generally higher, with stronger effects observed for increase in LOS and cost as well as gastrointestinal and urinary complications. Other outcomes were less pronounced, possibly because of smaller sample size. Overall, higher opioid prescription was associated with an increase in most postoperative complications with the strongest effect observed in thromboembolic, infectious and gastrointestinal complications, cost, and LOS. Increase in complication risk occurred stepwise, suggesting a dose-response gradient.

Observational data suggest an acquired prothrombotic state may contribute to the pathophysiology of COVID-19. These data include elevated D-dimers observed among many COVID-19 patients. We present a retrospective analysis of admission D-dimer, and D-dimer trends, among 1065 adult hospitalized COVID-19 patients, across 6 New York Hospitals. The primary outcome was all-cause mortality. Secondary outcomes were intubation and venous thromboembolism (VTE). Three-hundred-thirteen patients (29.4%) died, 319 (30.0%) required intubation, and 30 (2.8%) had diagnosed VTE. Using Cox proportional-hazard modeling, each 1 μg/ml increase in admission D-dimer level was associated with a hazard ratio (HR) of 1.06 (95%CI 1.04–1.08, p < 0.0001) for death, 1.08 (95%CI 1.06–1.10, p < 0.0001) for intubation, and 1.08 (95%CI 1.03–1.13, p = 0.0087) for VTE. Time-dependent receiver-operator-curves for admission D-dimer as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.694, 0.621, and 0.565 respectively. Joint-latent-class-modeling identified distinct groups of patients with respect to D-dimer trend. Patients with stable D-dimer trajectories had HRs of 0.29 (95%CI 0.17–0.49, p < 0.0001) and 0.22 (95%CI 0.10–0.45, p = 0.0001) relative to those with increasing D-dimer trajectories, for the outcomes death and intubation respectively. Patients with low-increasing D-dimer trajectories had a multivariable HR for VTE of 0.18 (95%CI 0.05–0.68, p = 0.0117) relative to those with high-decreasing D-dimer trajectories. Time-dependent receiver-operator-curves for D-dimer trend as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.678, 0.699, and 0.722 respectively. Although admission D-dimer levels, and D-dimer trends, are associated with outcomes in COVID-19, they have limited performance characteristics as prognostic tests.

Background Multimodal analgesia is increasingly considered routine practice in joint arthroplasties, but supportive large-scale data are scarce. The authors aimed to determine how the number and type of analgesic modes is associated with reduced opioid prescription, complications, and resource utilization. Methods Total hip/knee arthroplasties (N = 512,393 and N = 1,028,069, respectively) from the Premier Perspective database (2006 to 2016) were included. Analgesic modes considered were opioids, peripheral nerve blocks, acetaminophen, steroids, gabapentin/pregabalin, nonsteroidal antiinflammatory drugs, cyclooxygenase-2 inhibitors, or ketamine. Groups were categorized into “opioids only” and 1, 2, or more than 2 additional modes. Multilevel models measured associations between multimodal analgesia and opioid prescription, cost/length of hospitalization, and opioid-related adverse effects. Odds ratios or percent change and 95% CIs are reported. Results Overall, 85.6% (N = 1,318,165) of patients received multimodal analgesia. In multivariable models, additions of analgesic modes were associated with stepwise positive effects: total hip arthroplasty patients receiving more than 2 modes (compared to “opioids only”) experienced 19% fewer respiratory (odds ratio, 0.81; 95% CI, 0.70 to 0.94; unadjusted 1.0% [N = 1,513] vs. 2.0% [N = 1,546]), 26% fewer gastrointestinal (odds ratio, 0.74; 95% CI, 0.65 to 0.84; unadjusted 1.5% [N = 2,234] vs. 2.5% [N = 1,984]) complications, up to a –18.5% decrease in opioid prescription (95% CI, –19.7% to –17.2%; 205 vs. 300 overall median oral morphine equivalents), and a –12.1% decrease (95% CI, –12.8% to –11.5%; 2 vs. 3 median days) in length of stay (all P &lt; 0.05). Total knee arthroplasty analyses showed similar patterns. Nonsteroidal antiinflammatory drugs and cyclooxygenase-2 inhibitors seemed to be the most effective modalities used. Conclusions While the optimal multimodal regimen is still not known, the authors’ findings encourage the combined use of multiple modalities in perioperative analgesic protocols.

In this cohort of hip and knee arthroplasty patients, anaesthesia type and perioperative medications were associated with increased odds for postoperative delirium. Our results support the notion that modifiable risk factors may exacerbate or attenuate risk for postoperative delirium.

Guidelines currently favor vitamin K antagonists or low-molecular-weight heparins for treatment of noncirrhotic portal vein thrombosis (ncPVT). Use of direct oral anticoagulants (DOACs) in PVT has been met with concern because of the lack of data. We conducted a retrospective study to investigate the efficacy and safety of DOACs for the treatment of ncPVT, and to compare them with standard therapies: 330 patients with ncPVT, followed-up for a mean 41.6 months, received warfarin (n = 108), enoxaparin (n = 70), rivaroxaban (n = 65), apixaban (n = 20), dabigatran (n = 8), fondaparinux (n = 2), or no anticoagulation (n = 57). The primary outcome was complete radiographic resolution (CRR) of PVT. Secondary outcomes included recanalization of occlusive PVT, cavernous transformation of the PV, development of chronic portal hypertensive symptoms (cPHS), and major bleeding. DOACs were associated with the highest CRR rates (dabigatran, 6/8 [75%]; apixaban, 13/20 [65%]; rivaroxaban, 42/65 [65%]). Enoxaparin was associated with a CRR rate similar to that of the DOACs (40/70 = 57%). Warfarin was associated with worse outcomes in this regard (CRR rate, 31% [33/108]; hazard ratio [HR] DOACs:warfarin, 2.91; 95% confidence interval [CI], 1.87-4.52; P &lt; .0001). DOACs were associated with recanalization rates similar to enoxaparin and greater than warfarin (HR DOACs:warfarin, 3.45; 95% CI, 1.93-6.18; P &lt; .0001). DOACs were associated with lower rates of cPHS, although this did not attain significance (DOACs, 8/93 [9%]; enoxaparin, 13/70 [19%]; warfarin, 31/108 [29%]). DOACs were associated with less major bleeding relative to warfarin (HR DOACs:warfarin, 0.20; 95% CI, 0.05-0.86; P = .0307). Patients harboring JAK2V617F, those with no evident predisposing factor for PVT, and those with occlusive thrombus demonstrated worse outcomes. DOACs appear effective and safe for the treatment of ncPVT.

The role of anesthesia techniques on perioperative outcomes on a population level has recently gained widespread interest. Although mainly neuraxial vs general anesthesia has been addressed, population-level data on the impact of peripheral nerve blocks (PNBs) are still lacking. Therefore, we investigated the association between PNB use and outcomes using retrospective data on 1,062,152 recipients of hip and knee arthroplasties (total hip arthroplasty [THA]/total knee arthroplasty [TKA]) from the national Premier Perspective database (2006-2013). Multilevel multivariable logistic regression models measured associations between PNB use and outcomes. Complications included cardiac, pulmonary, gastrointestinal and renal complications, cerebrovascular events, infections, wound complications, thromboembolic complications, inpatient falls, and mortality. Resource utilization variables included blood transfusions, intensive care unit admissions, opioid consumption, cost, and length of stay. Overall, 12.5% of patients received a PNB, with an increase over time particularly among TKAs. Peripheral nerve block use was associated with lower odds for most adverse outcomes mainly among patients with THA. Notable beneficial effects were seen for wound complications (odds ratio 0.60 [95% confidence interval, 0.49-0.74]) among THA recipients and pulmonary complications (odds ratio 0.83 [95% confidence interval, 0.72-0.94]) in patients with TKA. Peripheral nerve block use was significantly (P < 0.0001) associated with a -16.2% and -12.7% reduction in opioid consumption for patients with THA and TKA, respectively. In conclusion, our results indicate that PNBs might be associated with superior perioperative population-level outcomes. In light of the inability to establish a causal relationship and the presence of residual confounding, we strongly advocate for further prospective investigation, ideally in multicenter, randomized trials, to establish the potential impact of PNBs on outcomes on a population level.

Study Design. Retrospective population-based cohort analysis. Objective. Given the lack of large-scale data on the use and efficacy of multimodal analgesia in spine fusion surgery, we conducted a population-based analysis utilizing the nationwide claims-based Premier Healthcare database. Summary of Background Data. Multimodal analgesia, combining different pain signaling pathways to achieve additive and synergistic effects, is increasingly emerging as the standard of care. Methods. Cases of posterior lumbar fusion surgery were extracted (2006–2016). Opioid-only analgesia was compared to multimodal analgesia, that is, systemic opioid analgesia + either acetaminophen, steroids, gabapentinoids, ketamine, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, or neuraxial anesthesia (categorized into 1, 2, or >2 additional analgesic modes). Mixed-effects models measured associations between multimodal analgesia categories and outcomes, including opioid prescription dose, cost/length of hospitalization, and opioid-related complications. Odds ratios (ORs, or % change) and 95% confidence intervals (CIs) are reported. Results. Among 265,538 patients the incidence of multimodal analgesia was 61.1% (162,156); multimodal pain management—specifically when adding NSAIDs/COX-2 inhibitors to opioids—was associated with reduced opioid prescription (−13.3% CI −16.7 to −9.7%), cost (−2.9% CI −3.9 to −1.8%) and length of hospitalization (−7.3% CI −8.5 to −6.1%). Multimodal analgesia in general was associated with stepwise decreased odds for gastrointestinal complications (OR 0.95, 95% CI 0.88–1.04; OR 0.84, CI 0.75–0.95; OR 0.78, 95% CI 0.64–0.96), whereas odds were increased for postoperative delirium (OR 1.14, 95% CI 1.00–1.32; OR 1.33, 95% CI 1.11–1.59; OR 1.31, 95% CI 0.99–1.74), and counterintuitively- naloxone administration (OR 1.25, 95% CI 1.13–1.38; OR 1.56, 95% CI 1.37–1.77; OR 1.84, 95% CI 1.52–2.23) with increasing analgesic modes used: one, two, or more additional analgesic modes, respectively. Post-hoc analysis revealed that specifically gabapentinoid use increased odds of naloxone requirement by about 50%, regardless of concurrent opioid dose (P < 0.001). Conclusion. Although multimodal analgesia was not consistently implemented in spine fusion surgery, particularly NSAIDs and COX-2 inhibitors demonstrated opioid sparing effects. Moreover, results suggest a synergistic interaction between gabapentinoids and opioids, the former potentiating opioid effects resulting in greater naloxone requirement. Level of Evidence: 3

BackgroundWith an ageing population, the demand for joint arthroplasties and the burden of postoperative delirium is likely to increase. Given the lack of large-scale data, we investigated associations between perioperative risk factors and postoperative delirium in arthroplasty surgery.MethodsThis retrospective population-based cohort study, utilized national claims data from the all-payer Premier Healthcare database containing detailed billing information from >25% nationwide hospitalizations. Patients undergoing elective total hip/knee arthroplasty surgery (2006–2016) were included.The primary outcome was postoperative delirium, while potential risk factors included age, gender, race, insurance type, and modifiable exposures including anesthesia type, opioid prescription dose (low/medium/high), benzodiazepines, meperidine, non-benzodiazepine hypnotics, ketamine, corticosteroids, and gabapentinoids.ResultsAmong 1 694 795 patients’ postoperative delirium was seen in 2.6% (14 785/564 226) of hip and 2.9% (32 384/1 130 569) of knee arthroplasties. Multivariable models revealed that the utilization of long acting (OR 2.10 CI 1.82 to 2.42), combined long/short acting benzodiazepines (OR 1.74 CI 1.56 to 1.94), and gabapentinoids (OR 1.26 CI 1.16 to 1.36) was associated with increased odds of postoperative delirium. Lower odds of postoperative delirium were seen for neuraxial versus general anesthesia (OR 0.81 CI 0.70 to 0.93) and with the utilization of non-steroidal anti-inflammatory drugs (OR 0.85 CI 0.79 to 0.91) as well as cyclooxygenase-2 inhibitors (OR 0.82 CI 0.77 to 0.89). Age-stratified analysis revealed lower odds with high versus low opioid dose (OR 0.86 CI 0.76 to 0.98) in patients >65 years. Findings were consistent between hip and knee arthroplasties.ConclusionsIn this large national cohort, we identified various modifiable risk factors (including anesthesia type and pharmaceutical agents) for postoperative delirium, demonstrating possible prevention pathways.