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.

Anticoagulation and Neuraxial/Peripheral Anesthesia. Kaushal M, Rubin RE, Kaye AD, Gritsenko K. Anesthesiol Clin. 2017 Jun;35(2):e21-e39. doi: 10.1016/j.anclin.2017.01.002. Review. PMID:28526159

Novel anticoagulants (NAGs) have emerged as the preferred alternatives to vitamin K antagonists. In patients being considered for regional anesthesia, these drugs present a layer of complexity in the preprocedure evaluation. There are no established tests to monitor anticoagulant activity and our experience is short with these drugs. These authors believe it is important to review the relevant hematology, orthopedics, and anesthesiology literature to provide a valuable reference for the clinician who is met with these challenges. In addition to discussing NAGs, we also review the existing American Society of Regional Anesthesia guidelines for heparin, low-molecular-weight heparin, and antiplatelet agents.

Postoperative Pediatric Cerebellar Mutism After Posterior Fossa Surgery Jerry Y. Chao, MD,* Che Liu, BS,* Naveen Shetty, BA,* and Ushma Shah, MD†A A Case Rep. 2017 Apr 15;8(8):213-215. doi: 10.1213/XAA.0000000000000467. PMID:28118217

Cerebellar mutism syndrome (CMS) is a common complication of posterior fossa surgery that can confound the postanesthetic examination and have long-lasting impacts. There is confusion surrounding its precise description, diagnostic features, and associated morbidity. Here, we discuss the most up-to-date knowledge of CMS drawing from a clinical case in the context of 3 new reports: (1) an international consensus paper presenting a new proposed working definition by the Iceland Delphi Group, (2) a knowledge update by Gadgil et al, (3) and a review of neuroimaging-based data elucidating the etiology of CMS by Patay.

Risk of Epidural Hematoma after Neuraxial Techniques in Thrombocytopenic Parturients: A Report from the Multicenter Perioperative Outcomes Group. Lee LO, Bateman BT, Kheterpal S, Klumpner TT, Housey M, Aziz MF, Hand KW, MacEachern M, Goodier CG, Bernstein J, Bauer ME; Multicenter Perioperative Outcomes Group Investigators. Anesthesiology. 2017 Jun;126(6):1053-1063. doi: 10.1097/ALN.0000000000001630. PMID:28383323

Thrombocytopenia has been considered a relative or even absolute contraindication to neuraxial techniques due to the risk of epidural hematoma. There is limited literature to estimate the risk of epidural hematoma in thrombocytopenic parturients. The authors reviewed a large perioperative database and performed a systematic review to further define the risk of epidural hematoma requiring surgical decompression in this population. The authors performed a retrospective cohort study using the Multicenter Perioperative Outcomes Group database to identify thrombocytopenic parturients who received a neuraxial technique and to estimate the risk of epidural hematoma. Patients were stratified by platelet count, and those requiring surgical decompression were identified. A systematic review was performed, and risk estimates were combined with those from the existing literature.

Exparel/Peripheral Catheter Use in the Ambulatory Setting and Use of Peripheral Catheters Postoperatively in the Home Setting. Bromberg AL, Dennis JA, Gritsenko K. Curr Pain Headache Rep. 2017 Mar;21(3):13. doi: 10.1007/s11916-017-0605-0. Review. PMID:28271332

With the increasing number of ambulatory surgeries being performed, regional anesthesia has become an increasingly popular anesthetic modality, and many choices exist to provide efficient, effective quality perioperative analgesia. In this paper, we will review the various regional anesthesia options in addition to the advantages and disadvantages of each. Lastly, we will discuss liposomal bupivicaine, a long acting local anesthetic, and its future role in the anesthesiologist's armamentarium. The aim of the publication is to provide a general overview of regional anesthesia as well as to discuss the advantages and disadvantages of this modality. Additionally, we sought to review the basics of liposomal bupivicaine as well as the relevant literature.

The Anatomic Relationship of the Tibial Nerve to the Common Peroneal Nerve in the Popliteal Fossa: Implications for Selective Tibial Nerve Block in Total Knee Arthroplasty. Silverman ER, Vydyanathan A, Gritsenko K, Shaparin N, Singh N, Downie SA, Kosharskyy B. Pain Res Manag. 2017;2017:7250181. doi: 10.1155/2017/7250181. Epub 2017 Feb 2. PMID:28260964

A recently described selective tibial nerve block at the popliteal crease presents a viable alternative to sciatic nerve block for patients undergoing total knee arthroplasty. In this two-part investigation, we describe the effects of a tibial nerve block at the popliteal crease. Methods. In embalmed cadavers, after the ultrasound-guided dye injection the dissection revealed proximal spread of dye within the paraneural sheath. Consequentially, in the clinical study twenty patients scheduled for total knee arthroplasty received the ultrasound-guided selective tibial nerve block at the popliteal crease, which also resulted in proximal spread of local anesthetic. A sensorimotor exam was performed to monitor the effect on the peroneal nerve. Results. In the cadaver study, dye was observed to spread proximal in the paraneural sheath to reach the sciatic nerve. In the clinical observational study, local anesthetic was observed to spread a mean of 4.7 + 1.9 (SD) cm proximal to popliteal crease. A negative correlation was found between the excess spread of local anesthetic and bifurcation distance. Conclusions. There is significant proximal spread of local anesthetic following tibial nerve block at the popliteal crease with possibility of the undesirable motor blocks of the peroneal nerve.

Impact of obesity on post-dural puncture headache. Song J, Zhang T, Choy A, Penaco A, Joseph V. Int J Obstet Anesth. 2017 May;30:5-9. doi: 10.1016/j.ijoa.2016.10.009. Epub 2016 Oct 29. PMID:28012862

Previous studies have suggested an inverse relationship between obesity and development of post-dural puncture headache following spinal anesthesia. However, few have investigated the relationship between obesity and headaches after accidental dural puncture with an epidural needle. This study explored whether obesity has any association with headaches following an accidental dural puncture.

Records of patients who received epidural analgesia for labor and vaginal delivery between January 2011 and June 2015 were reviewed. Body mass index, American Society of Anesthesiologists Physical Status and age were analyzed. Chi-squared analysis was performed to determine the relationship between the incidence and severity of post-dural puncture headaches and body mass index.

Enolate-Forming Compounds as a Novel Approach to Cytoprotection. LoPachin RM, Geohagen BC, Nordstrøm LU, Gavin T. Chem Res Toxicol. 2016 Dec 19;29(12):2096-2107. Epub 2016 Dec 6. Review. PMID:27989140

Evidence from laboratory studies and clinical trials suggests that plant-derived polyphenolic compounds such as curcumin, resveratrol, or phloretin might be useful in the treatment of certain diseases (e.g., Alzheimer's disease) and acute tissue injury states (e.g., spinal cord trauma). However, despite this potential, the corresponding chemical instability, toxic potential, and low bioavailability of these compounds could limit their ultimate clinical relevance. We have shown that pharmacophores of curcumin (e.g., 2-acetylcyclopentanone) and phloretin (e.g., 2',4',6'-trihydroxyacetophenone; THA) can provide cytoprotection in cell culture and animal models of oxidative stress injury. These pharmacophores are 1,3-dicarbonyl and polyphenol derivatives, the enol groups of which can ionize in biological solutions to form an enolate. This carbanionic moiety can chelate metal ions and, as a nucleophile, can scavenge toxic electrophiles (e.g., acrolein, 4-hydroxy-2-nonenal, and N-acetyl-p-benzoquinone imine) involved in many pathogenic conditions. Aromatic derivatives such as THA can also trap free oxygen and nitrogen radicals and thereby provide another layer of cytoprotection. The multifunctional character of these enolate-forming compounds suggests an ability to block pathogenic processes (e.g., oxidative stress) at several steps. The purpose of this review is to discuss research supporting our theory that enolate formation is a significant cytoprotective property that represents a platform for development of pharmacotherapeutic approaches to a variety of toxic and pathogenic conditions. Our discussion will focus on mechanism and structure-activity studies that define enolate chemistry and their corresponding relationships to cytoprotection.

Review of perioperative pain management of opioid-dependent patients. Vadivelu N, Mitra S, Kai AM, Kodumudi G, Gritsenko K. J Opioid Manag. 2016 Jul-Aug;12(4):289-301. doi: 10.5055/jom.2016.0344. PMID:27575830

Opioid dependence can occur due to prescription opioid use, recreational opioid use, or as a result of opioid use for the treatment of drug addiction. Pain control in these patients is truly a challenge. It is important to understand the patient's condition such as the phenomenon of drug dependence, drug addiction, and pseudoaddiction to provide effective analgesia. This may be accomplished using appropriate multimodal therapies and by treatment of coexisting diseases such as anxiety. The goal is to provide effective analgesia, prevent cognitive and emotional problems, and produce a positive postoperative rehabilitation process. Multimodal options include pharmacological and nonpharmacological approaches, psychological support, and interventional pain procedures, all focused toward providing optimal pain control while preventing undertreatment, withdrawal symptoms, and other complications.

Neuraxial Anesthesia in Parturients with Low Platelet Counts. Bernstein J, Hua B, Kahana M, Shaparin N, Yu S, Davila-Velazquez J. Anesth Analg. 2016 Jul;123(1):165-7. doi: 10.1213/ANE.0000000000001312. PMID:27159067

The obstetric anesthesiologist must consider the risk of spinal-epidural hematoma in patients 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/mm) 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/mm was 1.2%.

New Chronic Pain Treatments in the Outpatient Setting: Review Article. Grandhe R, Souzdalnitski D, Gritsenko K. Curr Pain Headache Rep. 2016 May;20(5):33. doi: 10.1007/s11916-016-0563-y. Review. PMID:27038972

Chronic pain is an issue encountered by many health care providers in their routine clinical practice. In addition to generalized patient suffering, this condition has significant clinical, psychological, and socioeconomic impact due to its widespread occurrence. The landscape of chronic pain management has been changing rapidly with an array of treatment innovations, better understanding of established therapies, and care coordination across specialties. In this article, we have reviewed emerging new modalities as well as transformation of established therapies by interventional, pharmacologic, rehabilitative, psychological, complimentary, and interdisciplinary approaches.

Comparison of Index Hospitalization Costs Between Robotic CABG and Conventional CABG: Implications for Hybrid Coronary Revascularization. Leyvi G, Schechter CB, Sehgal S, Greenberg MA, Snyder M, Forest S, Mais A, Wang N, DeLeo P, DeRose JJ Jr. J Cardiothorac Vasc Anesth. 2016 Jan;30(1):12-8. doi: 10.1053/j.jvca.2015.07.031. Epub 2015 Jul 29. PMID:26597467

To compare the direct costs of the index hospitalization and 30-day morbidity and mortality incurred during robotic and conventional coronary artery bypass grafting at a single institution based on hospital clinical and financial records.