Phentolamine Reverses Epinephrine-Enhanced Skin Antinociception of Dibucaine in Rats

BACKGROUND: The objective of the experiment was to assess the antinociceptive effect of dibucaine, bupivacaine, and epinephrine. To assess the mechanism of action of the interaction between dibucaine and epinephrine, phentolamine, a nonselective α-adrenergic antagonist, was added to the mixture. METHODS: We assessed sensory blockade with these drugs by injecting 0.6 mL of drug-in-saline in the dorsal thoracolumbar area of rats; pinprick of the "wheal" formed by the injectate was the area targeted for stimulation to elicit a cutaneous trunci muscle reflex. The sensory block of dibucaine was compared with that of bupivacaine or epinephrine. Drug–drug interactions were analyzed by isobologram. Phentolamine was added to investigate the antinociceptive effect of dibucaine coinjected with epinephrine. RESULTS: We demonstrated that dibucaine, epinephrine, and bupivacaine produced dose-dependent skin antinociception. On the median effective dose (ED50) basis, the potency was higher for epinephrine (mean, 0.011 [95% confidence interval {CI}, 0.007–0.015] μmol) than for dibucaine (mean, 0.493 [95% CI, 0.435–0.560] μmol) (P

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Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study

BACKGROUND: Approximately 50 million US patients undergo ambulatory surgery annually. Postoperative opioid overprescribing is problematic, yet many patients report inadequate pain relief. In major inpatient surgery, intraoperative single-dose methadone produces better analgesia and reduces opioid use compared with conventional repeated dosing of short-duration opioids. This investigation tested the hypothesis that in same-day ambulatory surgery, intraoperative methadone, compared with short-duration opioids, reduces opioid consumption and pain, and determined an effective intraoperative induction dose of methadone for same-day ambulatory surgery. METHODS: A double-blind, dose-escalation protocol randomized 60 patients (2:1) to intraoperative single-dose intravenous methadone (initially 0.1 then 0.15 mg/kg ideal body weight) or conventional as-needed dosing of short-duration opioids (eg, fentanyl, hydromorphone; controls). Intraoperative and postoperative opioid consumption, pain, and opioid side effects were assessed before discharge. Patient home diaries recorded pain, opioid use, and opioid side effects daily for 30 days postoperatively. Primary outcome was in-hospital (intraoperative and postoperative) opioid use. Secondary outcomes were 30 days opioid consumption, pain intensity, and opioid side effects. RESULTS: Median (interquartile range) methadone doses were 6 (5–6) and 9 (8–9) mg in the 0.1 and 0.15 mg/kg methadone groups, respectively. Total opioid consumption (morphine equivalents) in the postanesthesia care unit was significantly less compared with controls (9.3 mg, 1.3–11.0) in subjects receiving 0.15 mg/kg methadone (0.1 mg, 0.1–3.3; P

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Mixing Studies in Patients With Prolonged Activated Partial Thromboplastin Time or Prothrombin Time

BACKGROUND: Patients presenting for surgery may have isolated or combined prolonged activated partial thromboplastin time (aPTT) and/or prothrombin time (PT). In patients not receiving anticoagulants or with no identifiable cause for abnormal clot formation, a mixing study is performed. The index of circulating anticoagulant (ICA) has been used to predict the presence of an inhibitor, usually a lupus anticoagulant. METHODS: We retrospectively reviewed the results of mixing studies performed at Northwestern Memorial Hospital, between January 1, 2010 and February 29, 2012. We determined the number of samples that normalized or remained prolonged, the clotting factors associated with prolonged test results, and the presence of coagulation inhibitors. We calculated the ICA in the samples with prolonged aPTT and PT to determine its ability to predict a lupus anticoagulant. The primary comparison of interest was the diagnostic utility of the ICA at cutoff values of 11% for predicting the presence of lupus anticoagulant. RESULTS: There were 269 mixing studies performed: 131 samples with prolonged aPTT; 95 with prolonged PT; and 43 with both prolonged aPTT and prolonged PT. Of the samples with a prolonged aPTT, 55 of 131 (42%) normalized, 36 of 131 (27%) partially corrected, and 40 of 131 (31%) remained prolonged. Thirty-three of 95 samples (35%) with prolonged PT normalized, while 62 of 95 (65%) remained prolonged. Eight of 43 (19%) mixing studies of patients with prolonged PT and aPTT normalized; the aPTT normalized, but the PT remained prolonged in 17 of 43 (39%); the PT normalized, but the aPTT remained prolonged in 7 of 43 (16%); and both tests remained prolonged in 11 of 43 (26%) samples. Prolongations in the aPTT were primarily associated with low activities of CF XII, while the majority of the prolongations in PT were secondary to low activities in CF VII. Combined prolongations were secondary to deficiencies in both the intrinsic and extrinsic as well as the common pathways. An ICA >11% had 100% (95% CI, 59%–100%) sensitivity, 53% (95% CI, 35%–70%) specificity, and 77% (95% CI, 62%–92%) accuracy in predicting the presence of lupus anticoagulant in patients with prolonged aPTT. CONCLUSIONS: Normalization of the aPTT and PT in a mixing study was associated with low clotting factor activity. The ICA may be helpful in predicting the presence of a lupus anticoagulant. As anesthesiologists take ownership of the perioperative surgical home, we need to understand the clinical implications of the results of mixing studies. Accepted for publication April 12, 2018. Funding: Departmental. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Honorio T. Benzon, MD, Northwestern University Feinberg School of Medicine, 251 E Huron, Feinberg Pavilion, 5–704, Chicago, IL 60611. Address e-mail to h-benzon@northwestern.edu. © 2018 International Anesthesia Research Society

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Opening the Black Box: Understanding the Science Behind Big Data and Predictive Analytics

Big data, smart data, predictive analytics, and other similar terms are ubiquitous in the lay and scientific literature. However, despite the frequency of usage, these terms are often poorly understood, and evidence of their disruption to clinical care is hard to find. This article aims to address these issues by first defining and elucidating the term big data, exploring the ways in which modern medical data, both inside and outside the electronic medical record, meet the established definitions of big data. We then define the term smart data and discuss the transformations necessary to make big data into smart data. Finally, we examine the ways in which this transition from big to smart data will affect what we do in research, retrospective work, and ultimately patient care. Accepted for publication March 22, 2018. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Ira S. Hofer, MD, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA 90095. Address e-mail to ihofer@mednet.ucla.edu. © 2018 International Anesthesia Research Society

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Reversing Cholinergic Bronchoconstriction by Common Inotropic Agents: A Randomized Experimental Trial on Isolated Perfused Rat Lungs

BACKGROUND: The ability of inotropic agents to alter airway reactivity and lung tissue mechanics has not been compared in a well-controlled experimental model. Therefore, we compared the potential to alter lung tissue viscoelasticity and bronchodilator effects of commonly used inotropic agents in an isolated perfused rat lung model. METHODS: After achieving steady state lung perfusion, sustained bronchoconstriction was induced by acetylcholine (ACh). Isolated rat lungs were then randomly allocated to 6 groups treated with either saline vehicle (n = 8) or incremental concentrations of inotropes (adrenaline, n = 8; dopamine, n = 7; dobutamine, n = 7; milrinone, n = 8; or levosimendan, n = 6) added to the whole-blood perfusate. Airway resistance (Raw), lung tissue damping (G), and elastance were measured under baseline conditions, during steady-state ACh-induced constriction and for each inotrope dose. RESULTS: No change in Raw was observed after addition of the saline vehicle. Raw was significantly lower after addition of dopamine (maximum difference [95% CI] of 29 [12–46]% relative to the saline control, P = .004), levosimendan (58 [39–77]%, P

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The Effect of Labor Epidural Analgesia on Breastfeeding Outcomes: A Prospective Observational Cohort Study in a Mixed-Parity Cohort

BACKGROUND: The effect of labor epidural analgesia (LEA) on successful breastfeeding has been evaluated in several studies with divergent results. We hypothesized that LEA would not influence breastfeeding status 6 weeks postpartum in women who intended to breastfeed in an environment that encourages breastfeeding. METHODS: In this prospective observational cohort study, a total of 1204 women intending to breastfeed, delivering vaginally with or without LEA, were included; breastfeeding was recorded at 3 days and 6 weeks postpartum. Primary outcome was breastfeeding at 6 weeks, and the χ2 test was used for comparisons between women delivering with and without LEA, according to parity status and previous breastfeeding experience. Total epidural fentanyl dose and oxytocin use (yes/no) were recorded. A multivariable logistic regression was performed to assess factors affecting breastfeeding at 6 weeks. RESULTS: The overall breastfeeding rate at 6 weeks was 76.9%; it was significantly lower among women delivering with LEA (74.0%) compared with women delivering without LEA (83.4%; P

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Readiness for Discharge After Foot and Ankle Surgery Using Peripheral Nerve Blocks: A Randomized Controlled Trial Comparing Spinal and General Anesthesia as Supplements to Nerve Blocks

BACKGROUND: Neuraxial anesthesia is often viewed as superior to general anesthesia but may delay discharge. Comparisons do not typically use multimodal analgesics and nerve blockade. Combining nerve blockade with general anesthesia may reduce pain, opioid consumption, and nausea. We hypothesized that general anesthesia (with nerve blocks) would lead to earlier readiness for discharge, compared to spinal anesthesia (with nerve blocks). METHODS: All patients underwent ambulatory foot and ankle surgery, with a predicted case duration of 1–3 hours. All patients received popliteal and adductor canal nerve blocks using bupivacaine and dexamethasone. No intraoperative opioids were administered. All patients received ondansetron, dexamethasone, ketamine, and ketorolac. Patients, data collectors, and the data analyst were not informed of group assignment. Patients were randomized to spinal or general anesthesia with concealed allocation. Spinal anesthesia was performed with mepivacaine and accompanied with propofol sedation. After general anesthesia was induced with propofol, a laryngeal mask airway was inserted, followed by sevoflurane and propofol. Time until ready for discharge, the primary outcome, was compared between groups after adjusting for age and surgery time using multivariable unconditional quantile regression. Secondary outcomes compared at multiple timepoints were adjusted for multiple comparisons using the Holm–Bonferroni step-down procedure. RESULTS: General anesthesia patients were ready for discharge at a median of 39 minutes earlier (95% confidence interval, 2–75; P = .038) versus spinal anesthesia patients. Patients in both groups met readiness criteria for discharge substantially before actual discharge. Pain scores at rest were higher among general anesthesia patients 1 hour after leaving the operating room (adjusted difference in means, 2.1 [95% confidence interval, 1.0–3.2]; P

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