Report from the 12th ICCVA in Beijing

Excerpt: Researchers in Munich measured endogenous cannabinoid levels in 30 patients undergoing cardiac surgery with the aid of CPB. The endocannabinoids are simple metabolites of arachidonic acid. The two molecules examined were N-arachidonoylethanolamine (AEA, also known as anandamide) and 2-arachidonoylglycerol (2-AG). These are agonists for central and peripheral G-protein-coupled endocannabinoid receptors known as CB1 and CB2, respectively. The endocannabinoids were measured at various points perioperatively during a general anesthetic that included midazolam, sufentanil, and isoflurane. AEA (initially at 0.4 ng/ml) declined to 0.3 upon induction of anesthesia, and it further declined to 0.2 ng/ml upon arrival to the ICU. 2-AG (starting at 40 ng/ml) peaked at 420 ng/ml during CPB. Accordingly, the two molecules did not move synchronously. Endocannabinoids inhibit endogenous adrenergic activity. Though AEA levels tended to decrease in these patients, the highest concentrations of AEA were associated with the administration of higher doses of norepinephrine. The authors note that CB1 antagonists have shown benefit in various types of experimental shock, and they propose that AEA-induced hypotension is part of the “post-pump syndrome.” Reviewer’s Comments: Cannabis has been used pharmaceutically since antiquity and was advocated by Paracelsus (1493-1541) and by Alice B. Toklas (1877-1967). An ethereal tincture of the substance was one of the inhaled anesthetics proposed by ether pioneer Elton Romeo Smilie (1819-1889) (1). However, the isolated THC molecule was not identified until 1964. THC receptors were identified in the 1980s, but endogenous agonists were not found until the 1990s. AEA is produced by activated macrophages, while 2-AG comes largely from platelets. Both types of cells, of course, are impacted by CPB. The 10-fold increase in 2-AG likely reflects contact activation of platelets. It should be noted that multiple drug interactions intraoperatively can affect the various effects of these agents. For example, heparin was historically noted to be a “plasma clearing factor” because it triggers release of lipoprotein lipase and so clarifies the blood plasma from turbid lipid particles. Interestingly, heparin administration also increases phospholipase A2 activity in the plasma (2). That enzyme releases free arachidonic acid from lipoproteins, and the acid is processed into prostaglandins and other bioactive molecules. With the widespread administration of aspirin, alprostadil (PGE1), and NSAIDs, the metabolism of arachidonic acid is of broad interest in cardiovascular anesthesia. Furthermore, it is not just the metabolism of arachidonic acid that is affected by agents that are commonly used by patients presenting for cardiac surgery. The analgesic action of acetaminophen involves inhibition of the reuptake of AEA by neurons (3). Accordingly, the endocannabinoid receptors represent potentially intriguing targets for new pharmacological tools in cardiac anesthesia(4). 1. Stone ME, Meyer MR, Alston TA. Elton Romeo Smilie, the not-quite discoverer of ether anesthesia. Anesth Analg 2010; 110:195-7. 2. Nakamura H, Kim DK, Philbin DM, Peterson MB, Debros F, Koski G, Bonventre JV. Heparin-enhanced plasma phospholipase A2 activity and prostacyclin synthesis in patients undergoing cardiac surgery. J Clin Invest 1995; 95:1062-70. 3. Mallet C, Daulhac L, Bonnefont J, Ledent C, Etienne M, Chapuy E, Libert F, Eschalier A. Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. Pain 2008; 139:190-200. 4. Pacher P, Steffens S. The emerging role of the endocannabinoid system in cardiovascular disease. Semin Immunopathol 2009; 31:63-77. Late Outcomes After Carotid Artery Stenting Versus Carotid Endarterectomy. Insights From a Propensity-Matched Analysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry Sripal Bangalore, Deepak L. Bhatt, Joachim Röther et al. Circulation. 2010 Sep 14; 122(11):1091-100 Reviewer: Mohammed Minhaj, MD University of Chicago Medical Center Abstract Excerpt: Patients with carotid artery disease are often treated with either carotid artery stenting (CAS) or carotid endarterectomy (CEA). There continues to be debate of whether one treatment modality is superior to the other. The purpose of this study was to examine if there was a difference in late events (defined as two years after intervention) between the two interventions. The authors used the REACH (Reduction of Atherosclerosis for Continued Health) registry to review over 68,000 patients who had risk factor for, or established atherosclerotic disease. Patients who had either CAS or CEA were identified and followed prospectively for the occurrence of cardiovascular events. Primary outcome was death or stroke at 2-year follow-up. Of the over 68,000 patients, 3412 had a history of carotid revascularization, 1025 with CAS and 2387 with CEA. Propensity matching allowed the authors to identify comparable groups with respect to baseline characteristic, there were 836 patients in each group. At the end of 2 year follow-up there was no difference between CAS and CEA for the primary outcome (or for secondary/tertiary outcomes). The authors concluded that CAS was comparable to CEA for late outcomes.Excerpt: Patients with carotid artery disease are often treated with either carotid artery stenting (CAS) or carotid endarterectomy (CEA). There continues to be debate of whether one treatment modality is superior to the other. The purpose of this study was to examine if there was a difference in late events (defined as two years after intervention) between the two interventions. The authors used the REACH (Reduction of Atherosclerosis for Continued Health) registry to review over 68,000 patients who had risk factor for, or established atherosclerotic disease. Patients who had either CAS or CEA were identified and followed prospectively for the occurrence of cardiovascular events. Primary outcome was death or stroke at 2-year follow-up. Of the over 68,000 patients, 3412 had a history of carotid revascularization, 1025 with CAS and 2387 with CEA. Propensity matching allowed the authors to identify comparable groups with respect to baseline characteristic, there were 836 patients in each group. At the end of 2 year follow-up there was no difference between CAS and CEA for the primary outcome (or for secondary/tertiary outcomes). The authors concluded that CAS was comparable to CEA for late outcomes. Reviewer’s Comments: There continues to be debate in the literature regarding whether CEA or CAS is associated with improved late outcomes for patients with carotid disease. Several review articles have had conflicting results and the Cochrane reviews published between 2005-2009 on the subject have also been conflicting with respect to 30-day stroke/death results. Most studies demonstrated no difference between CAS or CEA, with reductions in myocardial infarctions in patients who had CAS. It should be noted however, that in these studies, patients typically had higher rates of coronary angioplasty/stenting when compared to patients who had CEA. This paper has the advantage of reviewing a much larger database of pa-