Priya A. Kumar

Perioperative Aspirin and Clonidine and Risk of Acute Kidney Injury A Randomized Clinical Trial

IMPORTANCE Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm. OBJECTIVE To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery. MAIN OUTCOMES AND MEASURES Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 μmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery. RESULTS Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58). CONCLUSIONS AND RELEVANCE Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01082874.

Simulator training enhances resident performance in transesophageal echocardiography.

Background:Standardized training via simulation as an educational adjunct may lead to a more rapid and complete skill achievement. The authors hypothesized that simulation training will also enhance performance in transesophageal echocardiography image acquisition among anesthesia residents. Methods:A total of 42 clinical anesthesia residents were randomized to one of two groups: a control group, which received traditional didactic training, and a simulator group, whose training used a transesophageal echocardiography–mannequin simulator. Each participating resident was directed to obtain 10 commonly used standard views on an anesthetized patient under attending supervision. Each of the 10 selected echocardiographic views were evaluated on a grading scale of 0 to 10, according to predetermined criteria. The effect of the intervention was assessed by using a linear mixed model implemented in SAS 9.3 (SAS Institute Inc., Cary, NC). Results:Residents in the simulation group obtained significantly higher-quality images with a mean total image quality score of 83 (95% CI, 74 to 92) versus the control group score of 67 (95% CI, 58 to 76); P = 0.016. On average, 71% (95% CI, 58 to 85) of images acquired by each resident in the simulator group were acceptable for clinical use compared with 48% (95% CI, 35 to 62) in the control; P = 0.021. Additionally, the mean difference in score between training groups was the greatest for the clinical anesthesia-1 residents (difference 24; P = 0.031; n = 7 per group) and for those with no previous transesophageal echocardiography experience (difference 26; P = 0.005; simulator n = 13; control n = 11). Conclusion:Simulation-based transesophageal echocardiography education enhances image acquisition skills in anesthesiology residents.

Combined versus sequential injection of mepivacaine and ropivacaine for supraclavicular nerve blocks.

Background: An ideal local anesthetic with rapid onset and prolonged duration has yet to be developed. Clinicians use mixtures of local anesthetics in an attempt to combine their advantages. We tested the hypothesis that sequential supraclavicular injection of 1.5% mepivacaine followed 90 secs later by 0.5% ropivacaine speeds onset of sensory block and prolongs duration of analgesia compared with simultaneous injection of the same 2 local anesthetics. Methods: We enrolled 103 patients undergoing surgery suitable for supraclavicular anesthesia. The primary outcome was time to 4-nerve sensory block onset in each of the 4 major nerve distributions: median, ulnar, radial, and musculocutaneous. Secondary outcomes included time to onset of first sensory block, time to complete motor block, duration of analgesia, pain scores at rest and with movement, and total opioid consumption. Outcomes were compared using the Kaplan-Meier analysis with the log-rank test or the analysis of variance, as appropriate. Results: Times to 4-nerve sensory block onset were not different between sequential and combined anesthetic administration. The time to complete motor block onset was faster in the combined group as compared with the sequential. There were not significant differences between the 2 randomized groups in other secondary outcomes, such as the time to onset of first sensory block, the duration of analgesia, the pain scores at rest or with movement, or the total opioid consumption. Conclusions: Sequential injection of 1.5% mepivacaine followed 90 secs later by 0.5% ropivacaine provides no advantage compared with simultaneous injection of the same doses.

Influenza-binding antibodies immobilise influenza viruses in fresh human airway mucus

Airway mucus is thought to serve as a dynamic filter that can trap respiratory viruses in the dense mucin network [1], and quickly eliminate them along with airway mucus from the respiratory tract. Nevertheless, viruses must penetrate airway mucus to infect the airway epithelium, and we and others have found that various viruses can readily penetrate physiological mucus gels [2–4]. We were particularly interested in whether airway mucus can serve as a barrier against influenza viruses, due to the prevalence and health burden of seasonal outbreaks. It has been suggested that airway mucus protects against influenza by presenting sialylated “decoys” on mucins that bind to influenza haemagglutinin and trap the virions in mucus. Alternatively, we have shown that antibodies in cervicovaginal mucus can trap viruses via multiple low-affinity Fc–mucin bonds between antibodies on the virus surface and mucins, akin to a Velcro patch [4]. To gain insight into how airway mucus might serve as a barrier against influenza, we characterised the mobility of influenza virions and virus-like particles (VLPs) in human airway mucus using real-time high-resolution multiple particle tracking. Common influenza viruses are immobilised in fresh human airway mucus, probably by influenza-binding antibodies http://ow.ly/yxu0305bqh6

Brachial arterial pressure monitoring during cardiac surgery rarely causes complications

Background: Brachial arterial catheters better estimate aortic pressure than radial arterial catheters but are used infrequently because complications in a major artery without collateral flow are potentially serious. However, the extent to which brachial artery cannulation promotes complications remains unknown. The authors thus evaluated a large cohort of cardiac surgical patients to estimate the incidence of related serious complications. Methods: The institutional Society of Thoracic Surgeons Adult Cardiac Surgery Database and Perioperative Health Documentation System Registry of the Cleveland Clinic were used to identify patients who had brachial artery cannulation between 2007 and 2015. Complications within 6 months after surgery were identified by International Classification of Diseases, Ninth Revision diagnostic and procedural codes, Current Procedural Terminology procedure codes, and Society of Thoracic Surgeons variables. The authors reviewed electronic medical records to confirm that putative complications were related plausibly to brachial arterial catheterization. Complications were categorized as (1) vascular, (2) peripheral nerve injury, or (3) infection. The authors evaluated associations between brachial arterial complications and patient comorbidities and between complications and in-hospital mortality and duration of hospitalization. Results: Among 21,597 qualifying patients, 777 had vascular or nerve injuries or local infections, but only 41 (incidence 0.19% [95% CI, 0.14 to 0.26%]) were potentially consequent to brachial arterial cannulation. Vascular complications occurred in 33 patients (0.15% [0.10 to 0.23%]). Definitely or possibly related infection occurred in 8 (0.04% [0.02 to 0.08%]) patients. There were no plausibly related neurologic complications. Peripheral arterial disease was associated with increased risk of complications. Brachial catheter complications were associated with prolonged hospitalization and in-hospital mortality. Conclusions: Brachial artery cannulation for hemodynamic monitoring during cardiac surgery rarely causes complications.

Aspirin in patients with previous percutaneous coronary intervention undergoing noncardiac surgery

Noncardiac surgery is common, with more than 200 million annual procedures worldwide (1, 2). Despite the benefits of noncardiac surgery, major perioperative cardiovascular complications occur and are associated with mortality, prolonged hospitalization, and costs (3, 4). Physicians commonly encounter patients undergoing noncardiac surgery who have had a prior percutaneous coronary intervention (PCI) (5); these patients are at increased risk for major perioperative cardiovascular complications (59). In the POISE-2 (PeriOperative ISchemic Evaluation-2) trial, we randomly assigned 10010 patients having noncardiac surgery to receive aspirin or placebo and showed that aspirin did not prevent the primary composite outcome of death and nonfatal myocardial infarction but did increase the risk for major bleeding (1012). These results influenced perioperative guidelines (13, 14). We reported the 4 planned aspirin subgroup analyses in the main POISE-2 publication (11). When POISE-2 was designed, we did not plan a PCI subgroup analysis because we did not anticipate that physicians would enroll patients with a history of PCI. However, given that investigators enrolled 470 patients with prior PCI and the ongoing uncertainty about the effects of antiplatelet therapy for these patients (15, 16), we did this POISE-2 substudy to determine whether perioperative low-dose aspirin, compared with placebo, affected 30-day events in patients with previous PCI. Methods Design Overview POISE-2 was an international, randomized controlled, factorial trial that separately evaluated the effects of aspirin versus placebo and clonidine versus placebo in patients having noncardiac surgery. Patients were allocated in a 1:1:1:1 ratio to receive aspirin and clonidine, placebo and clonidine, aspirin and placebo, or placebo for both drugs. Full details of the trial design and results are reported elsewhere (1012). Institutional review boards approved the trial before recruitment started at participating centers. Supplement. Supplementary Documents Setting and Participants Patients aged 45 years or older who were having noncardiac surgery with an expected postoperative stay of at least 1 night were eligible if they had or were at risk for atherosclerotic disease. The trial excluded patients who received a bare-metal stent within 6 weeks or a drug-eluting stent within 1 year before randomization because of the risk for stent thrombosis associated with premature antiplatelet withdrawal. Patients who took nonstudy aspirin within 72 hours before surgery were also excluded to ensure unimpaired hemostasis before surgery. Participants were recruited in 135 centers in 23 countries from July 2010 to December 2013. Eighty-two centers from 21 countries enrolled patients with a history of PCI. Research personnel enrolled patients in an initiation stratum if they were not receiving long-term aspirin and in a continuation stratum if they were receiving long-term aspirin (defined as daily aspirin for at least 1 month within the 6 weeks before surgery). Patients in the aspirin continuation stratum had to discontinue aspirin therapy at least 3 days before surgery. Randomization and Interventions After giving written informed consent, patients were randomly assigned before surgery by a 24-hour computerized Internet system that concealed randomization. Block randomization, stratified by center and aspirin stratum, was used. Patients received aspirin or identical-appearing placebo (200 mg) within 4 hours before surgery and continued at a dosage of 100 mg/d for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed regular aspirin dosing. Study personnel assessed study drug adherence through nursing records in the hospital and through patient reporting after discharge. Patients, clinicians, data collectors, and outcome adjudicators were blinded to study drug allocation. Patients had a troponin measurement (or creatine kinaseMB if troponin was not available) 6 to 12 hours after surgery and on the first, second, and third days after surgery. Electrocardiography was done when an elevated troponin or creatine kinaseMB level was detected. Research personnel followed patients until 30 days after randomization, collected data, and submitted case report forms and supporting documentation directly to the data management system. Outcomes and Follow-up Outcomes evaluated in this PCI substudy included the primary outcome (a composite of death and nonfatal myocardial infarction) and secondary outcomes (myocardial infarction, all-cause mortality, vascular mortality, stroke, congestive heart failure, composite of major and life-threatening bleeding, major bleeding, life-threatening bleeding, and clinically important hypotension) at 30 days after randomization. Outcome definitions are reported in the Supplement. Blinded outcome adjudicators evaluated the events reported in this substudy, except for congestive heart failure and clinically important hypotension. Their decisions were used in the analyses. Statistical Analysis A statistical analysis plan was finalized before these substudy analyses were begun (Supplement). We expected aspirin to have a greater beneficial effect in patients with a history of PCI than in those without. We analyzed patients in the groups to which they were allocated, according to the intention-to-treat principle. Patients lost to follow-up before day 30 after randomization with no event reported were censored on the last day their status was known. All statistical analyses were done using SAS, version 9.4 (SAS Institute). For the primary and secondary outcomes, we did subgroup analyses based on whether patients had prior PCI (prior PCI vs. no prior PCI). For these subgroup analyses, we used Cox proportional hazards models that incorporated tests of interaction. These models adjusted for clonidine allocation. For the primary outcome, we tested for the proportional hazards assumption by including a timeaspirin allocation interaction term in the Cox proportional hazards model (time log-transformed). We found no evidence that the proportional hazards assumption had been violated; all P values were at least 0.55. We considered a P value for interaction less than 0.05 to be significant and to provide some evidence of a subgroup effect. In instances where the test for interaction was not significant, we considered the overall trial result (with the larger sample size) the likely best estimate of effect for all patients, including those within the subgroups. Estimates of the hazard ratios (HRs) and 2-sided 95% CIs were calculated using the Cox proportional hazards models. We also determined the KaplanMeier estimates of 30-day cumulative risk. We report between-group differences in proportions between the treatment groups as absolute risk reductions (ARRs) and increases (ARIs). We determined the 95% CIs for these differences. Among patients with a history of PCI, we did subgroup analyses based on the type of stent (bare-metal vs. drug-eluting), timing of PCI (1 year vs. >1 year before surgery), and preoperative use of an antiplatelet medication (use within 7 days vs. no use within 7 days before surgery) for the primary outcome. We used the same analytic approach as in the analyses comparing the prior-PCI versus no-prior-PCI subgroups. Role of the Funding Source POISE-2 was supported by grants from the Canadian Institutes of Health Research, the Australian National Health and Medical Research Council, and the Spanish Ministry of Health and Social Policy. Bayer Pharmaceuticals provided the aspirin used in the study, and Boehringer Ingelheim provided the clonidine and some funding. No donor or funder had a role in the design, conduct, data collection, data analyses, or manuscript preparation. The Population Health Research Institute (McMaster University, Hamilton, Ontario, Canada) was the trial coordinating center. The investigators and members of key committees and groups are reported in the Supplement. Results Figure 1 is the study flow diagram; 99.9% of the patients randomly assigned to a treatment group completed the 30-day follow-up. POISE-2 enrolled 470 patients with prior PCI (255, 119, 53, 41, and 2 patients had a bare-metal stent, drug-eluting stent, unknown type of stent, no stent, and uncertainty about whether a stent was used, respectively), of whom 234 were randomly assigned to receive aspirin and 236 placebo. The allocation to receive clonidine was similar between patients with prior PCI (233 patients [49.6%]) and those without (4776 patients [50.1%]) (P= 0.84). The median time from stent placement to noncardiac surgery was 64.0 months (interquartile range, 34.0 to 113.0 months). Figure 1. Study flow diagram. PCI= percutaneous coronary intervention. Table 1 presents the baseline characteristics, medication use, and aspirin strata of patients with and without a history of PCI, by treatment group. Patients with prior PCI had more known coronary artery disease, more commonly took antiplatelet and anticoagulant medications in the 7 days before surgery (nonstudy aspirin, thienopyridine, or direct thrombin or factor Xa inhibitors), and were more commonly in the aspirin continuation stratum than patients without prior PCI. Patients who had not had PCI before surgery were older; were more commonly female; more commonly had major surgery and urgent or emergent surgery; and were more likely to have a history of treated diabetes, hypertension, and smoking in the 2 years before surgery. Table 1. Baseline Characteristics, Medications, and Aspirin Strata Among Patients With and Without Prior PCI, by Treatment Group* Among patients with prior PCI, the baseline characteristics, medications, and aspirin strata were similar in the aspirin and placebo groups. Most patients (>85%) with PCI before surgery were in the continuation stratum; aspirin was withdrawn a median of 6 days (interquartile range, 4 to 8 days) before surge

Paravertebral Block for Thoracic Surgery

Local anesthetic injected into a wedge-shaped space lateral to the spinal nerves as they emerge from the intervertebral foramina produces somatosensory and sympathetic nerve blockade effective for anesthesia and for managing pain of unilateral origin from the chest and abdomen. Paravertebral blockade (PVB) is versatile and may be applied unilaterally or bilaterally. Unlike thoracic epidural, the PVB technique may be used to avoid contralateral sympathectomy, thereby minimizing hypotension and leading to better preservation of blood pressure. There are no reports on systemic toxicity associated with bilateral PVB despite the need for relatively large doses of local anesthetics. This review includes an important historic background and captures the resurgence of PVB-an almost lost technique. Thoracic PVB provides post-thoracotomy pain relief comparable with thoracic epidural analgesia (TEA) with lower side effects supported by moderate-quality evidence. The feasibility and potential of bilateral thoracic PVB for bilateral thoracic surgery appear practical. However, there is existing controversy in the assumption that thoracic PVB is a satisfactory, safer alternative when anticoagulation status is a contraindication to thoracic epidural placement. During the last 2 decades of systematic reviews and meta-analyses, both TEA and PVB have been deemed appropriate in the management of thoracic surgery. A multimodal approach to analgesia includes regional techniques for thoracic surgery that may reduce the likelihood of the development of postoperative complications and chronic pain. PURPOSE OF THIS REVIEW The authors evaluated current opinion, clinical practice, new multimodal adjuvants, regional anesthesia, and innovation and technology related PVB in the thoracic surgery patient population. The review focuses on history, techniques, application, ease of placement, and relative safety of this regional technique. For this review, studies and reference lists were retrieved from the Cochrane library, Embase, and Medline from January 1995 through January 2017. SUMMARY Existing evidence demonstrates noninferiority of thoracic PVB compared with TEA for postoperative analgesia, with fewer side effects for unilateral and bilateral thoracic surgery, including video-assisted thoracoscopy. The determining factors in selecting the regional technique of choice include the following: (1) tolerance of side effects associated with TEA, (2) consensus on best practice or technique, and (3) operator experience. There is no consensus on the optimal approach for thoracic PVB technique or any standardization when comparing the landmark, ultrasound-guided, or stimulation-based PVB approaches. Moreover, the efficacy of TEA compared with PVB in preventing post-thoracotomy chronic pain syndrome has not been investigated thoroughly and requires future clinical trials.

Pro: Patients at Risk for Spinal Cord Ischemia After Thoracic Endovascular Aortic Repairs Should Receive Prophylactic Cerebrospinal Fluid Drainage

horacic endovascular aortic repair (TEVAR) has become aneurysms were included and the extent of aortic coverage or Testablished as a less invasive option for the management of descending thoracic aortic diseases compared with conventional open surgical repair. TEVAR has reduced morbidity and mortality compared with open surgical repair, but still it is associated with a significant risk of spinal cord ischemia (SCI), which can lead to permanent paraplegia. The 2 major recognized medical interventions to prevent and treat spinal cord ischemia in patients undergoing TEVAR are arterial pressure augmentation and lumbar cerebrospinal fluid (CSF) drainage. Despite limited evidence from randomized controlled trials, the published clinical experience supports the effectiveness of CSF drainage as an adjunct for the treatment of patients with SCI and in prevention of permanent paraplegia as a consequence of TEVAR. Although there is little controversy regarding the use of lumbar CSF drainage for the treatment of SCI, considerable controversy exists as to whether preoperative insertion of a lumbar CSF drain is warranted as a prophylactic measure in patients undergoing TEVAR. Based on the existing clinical experience published in the medical literature, an argument can be made to support the routine use of prophylactic CSF drainage among patients undergoing TEVAR who are deemed preoperatively to be at high risk for SCI. The reported incidence of SCI after TEVAR ranges between 0% and 10.3%, with the average incidence being between 3% and 5%. Published clinical series suggested that the risk of SCI associated with TEVAR was less than that associated with open surgical repair; however, there was significant anatomic heterogeneity in these series. Indeed, most TEVAR procedures were performed for aortic pathology limited to the descending thoracic aorta. When patients with thoracoabdominal aortic

Acquired "Gerbode-like" defect in aortic valve endocarditis: an imposter for tricuspid regurgitation?

e v e t fi t a m w e m e i v 4 A59-YEAR-OLD woman with a bioprosthetic aortic valve was referred to the authors’ heart and vascular institute for rosthetic valve endocarditis with blood cultures positive for ethicillin-sensitive Staphylococcus aureus. The transesophaeal echocardiogram (TEE) showed mobile densities on the ortic and ventricular surfaces of the Carpentier-Edwards aortic alve leaflets. The patient was scheduled for an urgent valve eplacement with an aortic valve homograft. After an un-

PRO: Transesophageal Echocardiography Should Be Routinely Used for All Liver Transplant Surgeries

From the Department of Anesthesiology, University of North Carolina School of Medicine, UNC Hospitals, Chapel Hill, NC. Address reprint requests to Harendra Arora, MD, Department of Anesthesiology, N2198, University of North Carolina Hospitals, Campus Box 7010, Chapel Hill, NC. E-mail: harora@aims.unc.edu