Montifore Medical Center

Atchabahian, A., Schwartz, G., Hall, C. B., Lajam, C. M., & Andreae, M. H. (2012). Regional analgesia for improvement of long-term functional outcome after elective large joint replacement. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd010278

Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low. Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI) - 2.23 to 10.21; P value = 0.21, 3 studies, 140 participants, very low quality evidence).We did not perform further analyses because immediate adverse effects were not part of the explicit outcomes of any of these typically small studies, and long-term adverse events after regional anaesthesia are rare. None of the included studies elicited or reported long-term adverse effects like persistent nerve damage. More high-quality studies are needed to establish the effects of regional analgesia on function after major joint replacement, as well as on the risk of adverse events (falls). This work was in part supported by grant # 5KL2TR001071-03 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health.

Kosharskyy, B., Vydyanathan, A., Zhang, L., Shaparin, N., Geohagen, B. C., Bivin, W., … LoPachin, R. M. (2015). 2-Acetylcyclopentanone, an Enolate-Forming 1,3-Dicarbonyl Compound, Is Cytoprotective in Warm Ischemia-Reperfusion Injury of Rat Liver. Journal of Pharmacology and Experimental Therapeutics, 353(1), 150-158. doi:10.1124/jpet.114.221622

We have previously shown that 2-acetylcyclopentanone (2-ACP), an enolate-forming 1,3-dicarbonyl compound, provides protection in cell culture and animal models of oxidative stress. The pathophysiology of ischemia-reperfusion injury (IRI) involves oxidative stress, and, therefore, we determined the ability of 2-ACP to prevent this injury in a rat liver model. IRI was induced by clamping the portal vasculature for 45 minutes (ischemia phase), followed by recirculation for 180 minutes (reperfusion phase). This sequence was associated with substantial derangement of plasma liver enzyme activities, histopathological indices, and markers of oxidative stress. The 2-ACP (0.80-2.40 mmol/kg), administered by intraperitoneal injection 10 minutes prior to reperfusion, provided dose-dependent cytoprotection, as indicated by normalization of the IRI-altered liver histologic and biochemical parameters. The 2-ACP (2.40 mmol/kg) was also hepatoprotective when injected before clamping the circulation (ischemia phase). In contrast, an equimolar dose of N-acetylcysteine (2.40 mmol/kg) was not hepatoprotective when administered prior to reperfusion. Our studies to date suggest that during reperfusion the enolate nucleophile of 2-ACP limits the consequences of mitochondrial-based oxidative stress through scavenging unsaturated aldehyde electrophiles (e.g., acrolein) and chelation of metal ions that catalyze the free radical-generating Fenton reaction. The ability of 2-ACP to reduce IRI when injected prior to ischemia most likely reflects the short duration of this experimental phase (45 minutes) and favorable pharmacokinetics that maintain effective 2-ACP liver concentrations during subsequent reperfusion. These results provide evidence that 2-ACP or an analog might be useful in treating IRI and other conditions that have oxidative stress as a common molecular etiology.

Leyvi, G., Forest, S. J., Srinivas, V. S., Greenberg, M., Wang, N., Mais, A., … DeRose, J. J. (2014). Robotic Coronary Artery Bypass Grafting Decreases 30-Day Complication Rate, Length of Stay, and Acute Care Facility Discharge Rate Compared With Conventional Surgery. Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery, 9(5), 361-367. doi:10.1097/imi.0000000000000095. NIEHS (ROI - ES03830-25-28)

The objective of this study was to compare the short-term outcomes of robotic with conventional on-pump coronary artery bypass grafting (CABG).The study population included 2091 consecutive patients who underwent either conventional or robotic CABG from January 2007 to March 2012. Preoperative, intraoperative, and 30-day postoperative variables were collected for each group. To compare the incidence of rapid recovery between conventional and robotic CABG, the surrogate variables of early discharge and discharge to home (vs rehabilitation or acute care facility) were evaluated. A multivariate logistic regression analysis was used. One hundred fifty robotic and 1619 conventional CABG cases were analyzed. Multivariate logistic regression analysis demonstrated that robotic surgery was a strong predictor of lower 30-day complications [odds ratio (OR), 0.24; P = 0.005], short length of stay (OR, 3.31; P < 0.001), and decreased need for an acute care facility (OR, 0.55; P = 0.032). In the presence of complications (New York State Complication Composite), the robotic technique was not associated with a change in discharge status. In this retrospective review, robotic CABG was associated with a lower 30-day complication rate, a shorter length of stay, and a lower incidence of acute care facility discharge than conventional on-pump CABG. It may suggest a more rapid recovery to preoperative status after robotic surgery; however, only a randomized prospective study could confirm the advantages of a robotic approach.

Andreae, M. H., Carter, G. M., Shaparin, N., Suslov, K., Ellis, R. J., Ware, M. A., … Sacks, H. S. (2015). Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data. The Journal of Pain, 16(12), 1221-1232. doi:10.1016/j.jpain.2015.07.009

Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains underdiagnosed and difficult to treat. Inhaled cannabis may alleviate chronic neuropathic pain. Our objective was to synthesize the evidence on the use of inhaled cannabis for chronic neuropathic pain. We performed a systematic review and a meta-analysis of individual patient data. We registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane Central, PubMed, EMBASE, and AMED. We considered all randomized controlled trials investigating chronic painful neuropathy and comparing inhaled cannabis with placebo. We pooled treatment effects following a hierarchical random-effects Bayesian responder model for the population-averaged subject-specific effect. Our evidence synthesis of individual patient data from 178 participants with 405 observed responses in 5 randomized controlled trials following patients for days to weeks provides evidence that inhaled cannabis results in short-term reductions in chronic neuropathic pain for 1 in every 5 to 6 patients treated (number needed to treat = 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14). Our inferences were insensitive to model assumptions, priors, and parameter choices. We caution that the small number of studies and participants, the short follow-up, shortcomings in allocation concealment, and considerable attrition limit the conclusions that can be drawn from the review. The Bayes factor is 332, corresponding to a posterior probability of effect of 99.7%.

Bernstein, J., Hua, B., Kahana, M., Shaparin, N., Yu, S. & Davila-Velazquez, J. (2016). Neuraxial anesthesia in parturients with low platelet counts. Anesth Analg [Accepted].

The obstetric anesthesiologist must consider the risk of spinal-epidural hematoma in the patient with thrombocytopenia when choosing to provide neuraxial anesthesia. There are little data exploring this complication in the parturient. In this single center retrospective study of 20,244 obstetric patients, the incidence of peripartum thrombocytopenia (platelet count <100,000/mm3) was 1.8% (368 patients). Of these patients, 69% (256) received neuraxial anesthesia. No neuraxial hematoma occurred in any of our patients. The upper 95% confidence limit for spinal-epidural hematoma in patients who received neuraxial anesthesia with a platelet count of <100,000/mm3 was 1.2%.

Leyvi, G., Schechter, C. B., Sehgal, S., Greenberg, M. A., Snyder, M., Forest, S., … DeRose, J. J. (2016). Comparison of Index Hospitalization Costs Between Robotic CABG and Conventional CABG: Implications for Hybrid Coronary Revascularization. Journal of Cardiothoracic and Vascular Anesthesia, 30(1), 12-18. doi:10.1053/j.jvca.2015.07.031

The inflammatory response elicited by robotic CABG has not been well described. The goal of the present study is to compare the extent and time course of cytokine release following both conventional CABG and robotic CABG to clearly define the optimal timing for robotic surgery in the setting of the HCR. Research methods include a prospective observational study accessing inflammatory response after robotic versus conventional CABG by pro-inflammatory cytokines IL-6, IL-8, TNF-alpha and anti-inflammatory cytokine IL-10 over 48 hours of perioperative period.