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In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) guideline on the endoscopic management of choledocholithiasis modified the individual predictors of choledocholithiasis proposed in the widely referenced 2010 guideline to improve predictive performance. Nevertheless, the primary literature, especially for the 2019 iteration, is limited. We performed a systematic review with meta-analysis to examine the diagnostic performance of the 2010, and where possible the 2019, predictors. PROSPERO protocol CRD42020194226. A comprehensive literature search from 2001 to 2020 was performed to identify studies on the diagnostic performance of any of the 2010 and 2019 ASGE choledocholithiasis predictors. Identified studies underwent keyword screening, abstract review, and full-text review. The primary outcomes included multivariate odds ratios (ORs) and 95% confidence intervals for each criterion. Secondary outcomes were reported sensitivities, specificities, and positive and negative predictive value. A total of 20 studies met inclusion criteria. Based on reported ORs, of the 2010 guideline “very strong” predictors, ultrasound with stone had the strongest performance. Of the “strong” predictors, CBD > 6 mm demonstrated the strongest performance. “Moderate” predictors had inconsistent and/or weak performance; moreover, all studies reported gallstone pancreatitis as non-predictive of choledocholithiasis. Only one study examined the new predictor (bilirubin > 4 mg/dL and CBD > 6 mm) proposed in the 2019 guideline. Based on this review, aside from CBD stone on ultrasound, there is discordance between the proposed strength of 2010 choledocholithiasis predictors and their published diagnostic performance. The 2019 guideline appears to do away with the weakest 2010 predictors.

Amyloid beta (Aβ) is a major component of amyloid plaques, which are a key pathological hallmark found in the brains of Alzheimer's disease (AD) patients. We show that statins are effective at reducing Aβ in human neurons from nondemented control subjects, as well as subjects with familial AD and sporadic AD. Aβ is derived from amyloid precursor protein (APP) through sequential proteolytic cleavage by BACE1 and γ-secretase. While previous studies have shown that cholesterol metabolism regulates APP processing to Aβ, the mechanism is not well understood. We used iPSC-derived neurons and bimolecular fluorescence complementation assays in transfected cells to elucidate how altering cholesterol metabolism influences APP processing. Altering cholesterol metabolism using statins decreased the generation of sAPPβ and increased levels of full-length APP (flAPP), indicative of reduced processing of APP by BACE1. We further show that statins decrease flAPP interaction with BACE1 and enhance APP dimerization. Additionally, statin-induced changes in APP dimerization and APP-BACE1 are dependent on cholesterol binding to APP. Our data indicate that statins reduce Aβ production by decreasing BACE1 interaction with flAPP and suggest that this process may be regulated through competition between APP dimerization and APP cholesterol binding.

Fibromyalgia is a common and challenging chronic pain disorder with few, if any, highly effective and well-tolerated treatments. Alpha-lipoic acid (ALA) is a nonsedating antioxidant with evidence of efficacy in the treatment of symptomatic diabetic neuropathy that has not been evaluated in the setting of fibromyalgia treatment. Thus, we conducted a single-centre, proof-of-concept, randomized, placebo-controlled, crossover trial of ALA for the treatment of fibromyalgia. Twenty-seven participants were recruited, and 24 participants completed both treatment periods of the trial. The median maximal tolerated dose of ALA in this trial was 1663 mg/day. Treatment-emergent adverse events with ALA were infrequent and not statistically different from placebo. For the primary outcome of pain intensity, and for several other validated secondary outcomes, there were no statistically significant differences between placebo and ALA. A post hoc exploratory subgroup analysis showed a significant interaction between gender and treatment with a significant favourable placebo-ALA difference in pain for men, but not for women. Overall, the results of this trial do not provide any evidence to suggest promise for ALA as an effective treatment for fibromyalgia, which is predominantly prevalent in women. This negative clinical trial represents an important step in a collective strategy to identify new, better tolerated and more effective treatments for fibromyalgia.

Significant blood loss during cardiac surgery is associated with a dramatic increase in morbidity and mortality. Factor Eight Inhibitor Bypassing Activity (FEIBA), a hemostatic bypassing agent mainly used in hemophiliac patients, has also been used for intractable bleeding during cardiac surgical procedures in non-hemophiliac patients. However, concerns exist that its use may be linked to increased incidence of perioperative adverse effects including thrombotic complications.A systematic literature search was performed on MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases for all studies that reported the administration of FEIBA for treatment of bleeding during adult cardiac surgery in non-hemophiliac patients. After selecting the title and abstracts, two authors assessed the methodological quality of the full-text articles prior to final inclusion in the manuscript.The safety profile of FEIBA was determined through an aggregate count of adverse events. Major complications included renal failure, re-operation for unresolved bleeding, postoperative mortality, and thromboembolic events. Overall, there is insufficient robust evidence to make a definitive conclusion about the safety or efficacy of using of FEIBA as a hemostatic agent in the setting of cardiac surgery.

Resumo Justificativa e objetivos A ultrassonografia cardiaca no local de atendimento (USCLA) provou ser importante para orientar o processo de tomada de decisao clinica dos anestesiologistas. Treinar os residentes para fazer e interpretar uma USCLA e viavel e eficaz. No entanto, o grau de retencao do conhecimento apos o treinamento permanece um assunto de debate. Procuramos fornecer uma descricao do curriculo de quatro semanas do treinamento de USCLA e avaliar a retencao do conhecimento entre os residentes de anestesia seis meses apos a rotacao em USCLA. Metodos Uma analise prospectiva foi realizada com 11 residentes seniores de anestesia. Ao final da rotacao em USCLA, os participantes preencheram um questionario (avaliando o numero de exames ultrassonograficos concluidos, o conhecimento adquirido e o nivel de conforto dos residentes com a USCLA) e fizeram um exame de multipla escolha para USCLA, composto por perguntas escritas e baseadas em video. Seis meses depois, os participantes preencheram um questionario de acompanhamento e um exame similar. A autoavaliacao do conhecimento e os escores do exame foram comparados no final da rotacao e apos seis meses. Correlacoes de Spearman foram usadas para testar a relacao entre o numero de exames concluidos e os escores dos exames, o conhecimento percebido, os escores dos exames, o numero de exames e o conhecimento percebido. Resultados Os escores medios dos exames (50) foram: 44,1 no final da rotacao e 43 apos seis meses. Os residentes tiveram conhecimento percebido significativamente maior (10) no final da rotacao (8,0) que apos seis meses (5,5), p = 0,003. No final da rotacao, todos os residentes se sentiram confortaveis usando o aparelho de USCLA e, aos seis meses, 10/11 ainda se sentiam confortaveis. Todos os residentes haviam usado o USCLA em sua pratica clinica apos o final da rotacao e a razao mais citada para nao usar o USCLA com mais frequencia foi a falta de necessidade clinica percebida. Uma correlacao forte e estatisticamente significativa (rho = 0,804, p = 0,005) foi observada entre o numero de exames realizados durante a rotacao em USCLA e o conhecimento percebido em seis meses de seguimento. Conclusao Quatro semanas de treinamento intensivo de USCLA resultaram em aquisicao e retencao adequadas do conhecimento por seis meses.

The implementation of competency-based medical education in Canada has presented both unique opportunities and challenges for improving undergraduate procedural skills curricula. Despite the recognized importance of procedural skills, there remains a lack of national congruency in procedural training across medical schools that must be addressed. When undertaking such curricular development, obtaining learner feedback is a crucial step that can facilitate practical changes and address disparities. The purpose of the current study is to explore the perspectives and insights of recent medical graduates surrounding the clerkship procedural skills curriculum at a Canadian medical school. Six residents from a variety of program specialties participated in a semi-structured focus group interview discussing key aspects of procedural skill training. The focus group was later transcribed and qualitatively analyzed for themes. The results highlight barriers to competency-based procedural skill training involving time constraints and obtaining required evaluations, and the ability of students to self-advocate for learning opportunities. Participants note few opportunities to practice nasogastric tube insertion and casting in particular. Recommendations for curricular improvement are discussed, including options for curricular remediation and resident perspectives on which procedural skills undergraduate trainees should achieve competency in by graduation.

We report a case of a 72-year-old woman who experienced postictal episodes of trismus lasting several minutes on 6 occasions during a series of 18 episodes of electroconvulsive therapy (ECT). There was no clear relationship between the development of trismus and any medications used during the treatments. The patient had no adverse outcomes or discomfort, but the development of trismus can put patients at significant risk.

Background and objectives: Focused Cardiac Ultrasound (FoCUS) has proven instrumental in guiding anesthesiologists’ clinical decision-making process. Training residents to perform and interpret FoCUS is both feasible and effective. However, the degree of knowledge retention after FoCUS training remains a subject of debate. We sought to provide a description of our 4-week FoCUS curriculum, and to assess the knowledge retention among anesthesia residents at 6 months after FoCUS rotation. Methods: A prospective analysis involving eleven senior anesthesia residents was carried out. At end of FoCUS Rotation (EOR) participants completed a questionnaire (evaluating the number of scans completed and residents’ self-rated knowledge and comfort level with FoCUS), and a multiple-choice FoCUS exam comprised of written- and video-based questions. Six months later, participants completed a follow-up questionnaire and a similar exam. Self-rated knowledge and exam scores were compared at EOR and after 6 months. Spearman correlations were conducted to test the relationship between number of scans completed and exam scores, perceived knowledge and exam scores, and number of scans and perceived knowledge. Results: Mean exam scores (out of 50) were 44.1 at EOR and 43 at the 6-month follow-up. Residents had significantly higher perceived knowledge (out of 10) at EOR (8.0) than at the 6-month follow-up (5.5), p = 0.003. At the EOR, all trainees felt comfortable using FoCUS, and at 6 months 10/11 still felt comfortable. All the trainees had used FoCUS in their clinical practice after EOR, and the most cited reason for not using FoCUS more frequently was the lack of perceived clinical need. A strong and statistically significant (rho = 0.804, p = 0.005) correlation between number of scans completed during the FoCUS rotation and 6-month follow-up perceived knowledge was observed. Conclusion: Four weeks of intensive FoCUS training results in adequate knowledge acquisition and 6-month knowledge retention. Resumo: Justificativa e objetivos: A ultrassonografia cardíaca no local de atendimento (USCLA) provou ser importante para orientar o processo de tomada de decisão clínica dos anestesiologistas. Treinar os residentes para fazer e interpretar uma USCLA é viável e eficaz. No entanto, o grau de retenção do conhecimento após o treinamento permanece um assunto de debate. Procuramos fornecer uma descrição do currículo de quatro semanas do treinamento de USCLA e avaliar a retenção do conhecimento entre os residentes de anestesia seis meses após a rotação em USCLA. Métodos: Uma análise prospectiva foi realizada com 11 residentes seniores de anestesia. Ao final da rotação em USCLA, os participantes preencheram um questionário (avaliando o número de exames ultrassonográficos concluídos, o conhecimento adquirido e o nível de conforto dos residentes com a USCLA) e fizeram um exame de múltipla escolha para USCLA, composto por perguntas escritas e baseadas em vídeo. Seis meses depois, os participantes preencheram um questionário de acompanhamento e um exame similar. A autoavaliação do conhecimento e os escores do exame foram comparados no final da rotação e após seis meses. Correlações de Spearman foram usadas para testar a relação entre o número de exames concluídos e os escores dos exames, o conhecimento percebido, os escores dos exames, o número de exames e o conhecimento percebido. Resultados: Os escores médios dos exames (50) foram: 44,1 no final da rotação e 43 após seis meses. Os residentes tiveram conhecimento percebido significativamente maior (10) no final da rotação (8,0) que após seis meses (5,5), p = 0,003. No final da rotação, todos os residentes se sentiram confortáveis usando o aparelho de USCLA e, aos seis meses, 10/11 ainda se sentiam confortáveis. Todos os residentes haviam usado o USCLA em sua prática clínica após o final da rotação e a razão mais citada para não usar o USCLA com mais frequência foi a falta de necessidade clínica percebida. Uma correlação forte e estatisticamente significativa (rho = 0,804, p = 0,005) foi observada entre o número de exames realizados durante a rotação em USCLA e o conhecimento percebido em seis meses de seguimento. Conclusão: Quatro semanas de treinamento intensivo de USCLA resultaram em aquisição e retenção adequadas do conhecimento por seis meses. Keywords: POCUS, FoCUS, Knowledge retention, Education, Anesthesia, Palavras-chave: POCUS, USCLA, Retenção de conhecimento, Educação, Anestesia

Background: Chronic pain is a serious health issue impacting both the quality of life and productivity of patients.Chronic post-sternotomy pain (CPSP) is characterized by numbness, severe tenderness on palpation, allodynia, as well as constant pain across the anterior chest wall that can persist for months to years after sternotomy. All patients experience early post-operative pain following coronary artery bypass graft (CABG); unfortunately, approximately 30-40% of CABG patients subsequently develop CPSP. Methods: The current study is a prospective, double-blinded, randomized controlled trial. A sample size of 316 randomly assigned patients (n=158 per group) will provide an 80% power at a 2-sided α of 0.05 to detect a 40% decrease in CPSP incidence at 6 months. Eligible patients scheduled for elective, primary coronary artery bypass graft surgery will be randomly assigned to the CONTROL group, in which sternal retraction is conducted over 30 seconds (as per standard practice); or the SLOW group, in which sternal retraction is achieved over 15 minutes. Surgical and perioperative anesthesia protocols between the two groups are otherwise the same. Our primary outcome is the incidence of CPSP at 6 months. Secondary outcomes are: CPSP incidence at 3 and 12 months, daily sternal incision pain intensity (numeric rating scale (NRS)) at rest and while coughing, and daily analgesic consumption while in hospital and at 7 days postoperatively; pain quality, quality of life, and pain interference with daily function at 3, 6, and 12 months post-operatively.Discussion: Our randomized controlled trial will determine whether retracting the sternum more slowly for exposure of the heart during CABG surgery will decrease the incidence and/or severity of CPSP.ClinicalTrials.gov registration:NCT02697812 (03/03/2016

The optimal approach to postoperative analgesia in patients with bilateral diaphragmatic paralysis undergoing abdominal surgery remains unclear. We report a 69-year-old woman with bilateral diaphragmatic paralysis who underwent a laparoscopic hernia repair and an open laparotomy for reversal of a Hartmann procedure under general anesthesia. Postoperative analgesia was provided by intravenous opioid and epidural local anesthetic and opioid, respectively. The patient's trachea was successfully extubated at the end of both surgical procedures. Epidural analgesia was associated with better pain control and shorter intensive care unit stay.

Focused Cardiac Ultrasound (FoCUS) has proven instrumental in guiding anesthesiologists' clinical decision-making process. Training residents to perform and interpret FoCUS is both feasible and effective. However, the degree of knowledge retention after FoCUS training remains a subject of debate. We sought to provide a description of our 4-week FoCUS curriculum, and to assess the knowledge retention among anesthesia residents at 6 months after FoCUS rotation.A prospective analysis involving eleven senior anesthesia residents was carried out. At end of FoCUS Rotation (EOR) participants completed a questionnaire (evaluating the number of scans completed and residents' self-rated knowledge and comfort level with FoCUS), and a multiple-choice FoCUS exam comprised of written- and video-based questions. Six months later, participants completed a follow-up questionnaire and a similar exam. Self-rated knowledge and exam scores were compared at EOR and after 6 months. Spearman correlations were conducted to test the relationship between number of scans completed and exam scores, perceived knowledge and exam scores, and number of scans and perceived knowledge.Mean exam scores (out of 50) were 44.1 at EOR and 43 at the 6-month follow-up. Residents had significantly higher perceived knowledge (out of 10) at EOR (8.0) than at the 6-month follow-up (5.5), p=0.003. At the EOR, all trainees felt comfortable using FoCUS, and at 6 months 10/11 still felt comfortable. All the trainees had used FoCUS in their clinical practice after EOR, and the most cited reason for not using FoCUS more frequently was the lack of perceived clinical need. A strong and statistically significant (rho=0.804, p=0.005) correlation between number of scans completed during the FoCUS rotation and 6-month follow-up perceived knowledge was observed.Four weeks of intensive FoCUS training results in adequate knowledge acquisition and 6-month knowledge retention.

Background: Fibromyalgia is a common disorder characterized by chronic widespread pain, sleep disturbance, fatigue, depression, and cognitive dysfunction, resulting in substantial disability. As current analgesics provide incomplete relief and disabling side effects that aggravate fatigue and cognitive dysfunction, there is a need for new pain treatments with better efficacy and tolerability. Alpha-lipoic acid (ALA) is an antioxidant proven effective in painful diabetic neuropathy with minimal side effects. Objective: We hypothesize that this agent will provide benefits in fibromyalgia because of several similarities with neuropathic pain and also because it does not cause sedation, fatigue, or mental-slowing. To test this, we have designed a clinical trial that will assess pain, side effects, and other outcomes in participants with fibromyalgia. Methods: Using a crossover design, 24 adults with fibromyalgia will be randomly allocated to 1 of the 2 sequences of ALA and placebo. Participants will take capsules containing ALA or placebo for 4 weeks followed by a 1-week washout followed by a second 4-week treatment and 1-week washout period. ALA (or matching placebo) capsules will be titrated to 1800 mg/day over each 4-week period. The primary outcome will be mean daily pain intensity (0-10) during week 4 of each period. Secondary outcomes, assessed during week 4 of each period, will include global improvement, adverse events, mood, and quality of life. Results: This trial was registered in the International Standard Randomized Controlled Trial registry March 15, 2016 (Number ISRCTN58259979), and it attained ethics approval on December 3, 2016 (Queen’s University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board protocol number ANAE-287-15). The recruitment started in February 2017. Conclusions: This trial will provide evidence for the efficacy of ALA in fibromyalgia. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 58259979; www.isrctn.com/ISRCTN58259979 (Archived by WebCite at http://www.webcitation.org/6og9JdiyZ) [JMIR Res Protoc 2017;6(3):e41]

Simulation is an effective tool in medical education with debriefing as the cardinal educational component. Alternate debriefing strategies might further enhance the educational value of simulation. Here, we pilot a novel strategy that allows trainees to initiate debriefing at any point during the scenario, when they consider it necessary.With ethics approval, 8 postgraduate year 1 anesthesia residents (with no previous exposure to high-fidelity simulation) were randomly assigned to lead 2 of 8 scenarios with 2 debriefing strategies. With "debriefing-on-demand," residents had the option to initiate debriefing at any point in the scenario by activation of a "pause button"-in addition to undergoing conventional debriefing at the end of the scenario. Those randomized to "conventional debriefing" were debriefed only at the end of the scenario. All were allocated as team leader with both debriefing strategies and as a participant in remaining scenarios. Residents provided feedback regarding each method using Likert scales and completion of open-ended statements.Debriefing-on-demand was easily integrated into all scenarios, and most learners (88%) supported its use in future simulation sessions. The following 4 themes emerged from qualitative analyses: (1) improvements in the clarification and integration of knowledge, (2) reductions in stress/anxiety, (3) facilitated reflection on action, and (4) maintained realism comparable with conventional debriefing.Debriefing-on-demand was easily integrated into all scenarios and well received by these trainees new to simulation. Larger trials that use validated tools are needed to determine the absolute impact of debriefing-on-demand on stress levels and the overall learning value of simulation for trainees at different levels of training.

Cardiac complications stemming from intra-cranial hypertension may result from impaired intra-cellular Ca(2+) homeostasis. The aim of this study was to examine the effects of dantrolene, a blocker of sarcoplasmic reticulum (SR) Ca(2+) release, on myocardial dysfunction associated with intra-cranial hypertension in rats. Dantrolene (10 mg) with and without 15% mannitol was administered to halothane-anesthetized rats prior to induction of intra-cranial hypertension by subdural balloon inflation. Its effects were compared to 3% and 15% mannitol and 5% Pentaspan. Dantrolene with mannitol or 15% mannitol alone prevented the transient intra-cranial hypertension-induced hyperdynamic response and ensuing circulatory collapse that was found in animals pre-treated with 3% mannitol solution or pentaspan. Moreover, hemodynamic function was preserved irrespective of TnI cleavage. However, only animals treated with high dose 15% mannitol exhibited lower lipid peroxidation content in the heart. In contrast, pre-treatment with dantrolene alone did not prevent the cardiac complications associated with intra-cranial hypertension. In conclusion, 15% mannitol attenuated the cardiopulmonary complications associated with intra-cranial hypertension. Dantrolene without mannitol was without effect. Since mannitol exhibits free radical scavenging properties, protection could be the result of a decrease in oxidative stress after intra-cranial hypertension.

Background In addition to generating free radicals, stress-induced activation of the sympathetic nervous system results in hyperphosphorylation of the cardiac ryanodine receptor (RyR2)/calcium (Ca 2+ ) release channel on the sarcoplasmic reticulum, causing leaky channels. These events may contribute to cytosolic Ca 2+ overload and activation of Ca 2+ -dependent cytotoxic processes. Because myocardial dysfunction associated with intracranial hypertension is catecholamine mediated, we sought to determine in a rat model if hemodynamic changes are associated with an increase in oxidative stress, hyperphosphorylation of RyR2, and degradation of myofilament protein cardiac troponin I (TnI). Methods In halothane-anesthetized rats treated with saline, dimethyl sulfoxide (DMSO), or the synthetic calpain inhibitor calpeptin (3,500 μg), a subdural balloon catheter was inflated to induce intracranial hypertension. Hearts were excised, and RyR2 phosphorylation status and TnI degradation was determined with Western blot analysis. In separate experiments, treated rats were challenged with increasing doses of dobutamine 30 minutes after subdural balloon inflation. Results Elevating the intracranial pressure resulted in an increase in plasma catecholamines, as well as in 3,4-dihydroxybenzoic acid (DHBA), an indirect marker of HO· radical production, and left ventricular dysfunction in rats treated with saline or DMSO. There was evidence of hyperphosphorylation of RyR2 and TnI degradation (27 kD immunoreactive band). Calpeptin treatment improved left ventricular function; however, this had no effect on the phosphorylation status of RyR2 or TnI degradation levels. In addition, the myocardial responsiveness to dobutamine was augmented in rats with depressed myocardial function. Conclusion The present findings demonstrate that hemodynamic instability after intracranial hypertension is associated with oxidative stress and post-translational changes to RyR2 and TnI degradation. Despite this, the myocardial responsiveness to β 1 adrenergic stimulation is preserved in rats with depressed myocardial function.

The number of anesthesia providers required by the Canadian health care system remains controversial. Questions persist regarding both the adequacy of the current supply and what the future demand will be. The purpose of this study was to quantify the number and adequacy of anesthesia providers in 2002, and predict the same for the year 2007.All licensed health care facilities potentially employing anesthetic services were identified. On February 1(st), 2002 a questionnaire was mailed to each institution. On April 1(st), a second mailing was sent to non-responders. Those facilities that did not respond to either mailing were contacted by telephone.Responses were obtained from 831 of 891 (93%) health care facilities. Four hundred and twenty-six of the facilities employed anesthetic services. There were 1,610 operating rooms (ORs) in use daily, and 2,134 full-time equivalent (FTE) anesthesia providers were available to the institutions surveyed. Respondents identified an immediate need for 228 additional FTEs. Hospitals with less than five ORs or five FTEs reported higher vacancy rates than hospitals with greater than five ORs or five FTEs (P0.0001). Ontario (n = 85) and Quebec (n = 69) had the largest absolute deficits of FTEs and significantly greater odds of vacancies than western provinces (Ontario OR = 1.84, Quebec OR = 2.50). The projected need for 2007 was an additional 560 FTEs.This is the first study to survey a national census of "consumers" of anesthetic services: Canadian health care facilities. The results indicate substantial current and worsening future shortages of anesthesia providers in Canada.

To determine if central sympathetic blockade by dexmedetomidine, a selective alpha2 adrenergic receptor agonist, prevents cardiac dysfunction associated with intracranial hypertension (ICH) in a rat model. Following intracisternal administration of dexmedetomidine (1 μg · μl−1, 10 μL volume) or the stereoisomer levomedetomidine (1 μg· μL−1, 10 μL volume) in halothane-anesthetized rats, a subdural balloon catheter was inflated for 60 sec to produce ICH. Intracranial pressure, hemodynamic, left ventricular (LV) pressures and electrocardiographic (ECG) changes were recorded. Plasma and myocardial catecholamines and malondialdehyde (MDA) levels were measured. After levomedetomidine administration, subdural balloon inflation precipitated an increase in mean arterial pressure (149 ± 33% of baseline), heart rate (122 ± 19% of baseline), LV systolic pressure (LVP), LV end-diastolic pressure (LVEDP), LV developed pressure (LVDP), LV dP/dtmax and rate pressure product (RPP) (132 ± 19%, 260 ± 142%, 119 ± 15%, 126 ± 24% and 146 ± 33% of baseline value, respectively). ICH decelerated LVP fall (τ), as t increased from 7.75 ± 1. 1 to 14.37 ± 4.5 msec. Moreover, plasma norepinephrine levels were elevated ( 169 ± 50% of baseline) and there was the appearance of cardiac dysrhythmias and other ECG abnormalities. This response was transient and cardiac function deteriorated in a temporal manner. Intracisternal dexmedetomidine prevented the rise in plasma norepinephrine, blocked the ECG abnormalities, and preserved cardiac function. Moreover, dexmedetomidine attenuated the rise in MDA levels. The results demonstrate that dexmedetomidine attenuates cardiac dysfunction associated with ICH. Our results provide evidence for the role of central sympathetic hyperactivity in the development of cardiac dysfunction associated with ICH.

UNLABELLED After the administration of intrathecal strychnine, allodynia is manifested as activation of supraspinal sites involved in pain processing and enhancement of cardiovascular responses evoked by normally innocuous stimuli. The objective of this study was to investigate the effect of strychnine-induced allodynia on adrenergic neuronal activity in the C1 area of the rostral ventrolateral medulla (RVLM), a major site involved in cardiovascular regulation. The effect of intrathecal strychnine (40 microg) or saline followed by repeated hair deflection to caudal lumbar dermatomes in the urethane-anesthetized rat was assessed by measuring voltammetric changes in the RVLM catechol oxidation current (CA x OC), mean arterial pressure (MAP), and heart rate (HR). After the administration of intrathecal strychnine, hair deflection evoked a significant and sustained increase in the RVLM CA x OC and MAP (peak 146.4%+/-5.6% and 159%+/-18.4% of baseline, respectively; P < 0.05). There was a nonsignificant increase in HR (peak 128%+/-8.2%). In the absence of hair deflection, there was no demonstrable change. Intrathecal saline-treated rats failed to demonstrate changes in RVLM CA x OC, MAP, or HR. In the present study, we demonstrated that, after the administration of intrathecal strychnine, innocuous hair deflection evokes temporally related neuronal activation in the rat RVLM and an increase in MAP. This suggests that the RVLM mediates, at least in part, the cardiovascular responses during strychnine allodynia. IMPLICATIONS Neural injury-associated pain, as manifested by allodynia, is resistant to conventional treatment. In a rat model of allodynia, we demonstrated activation of the brain region involved in sympathetic control. Innovative therapies that target this region may be successful in managing this debilitating condition.

Intravenous antifibrinolytics are the gold standard for blood conservation during cardiac surgery. Recent evidence suggests that topical tranexamic acid administration also is effective, although the efficacy of combined topical and intravenous administration has never been reported. Combined administration may offer superior hemostasis while decreasing side effects. The current study explores the use of combined topical and intravenous tranexamic acid as a blood conservation strategy in cardiac surgery.Retrospective cohort.A single-center, academic, tertiary care hospital.One hundred sixty elective coronary artery bypass graft patients.A practice change allowed a retrospective comparison of postoperative chest tube drainage in patients with intravenous or combined (intravenous and topical) tranexamic acid.Chest tube drainage was decreased in the combined group at 3 (164.8 ± 102.2 v 242.7 ± 148.9 mL, p0.001), 6 (265.6 ± 163.7 v 358.8 ± 247.2 mL, p = 0.006), and 12 hours (374.3 ± 217.1 v 498.5 ± 336.6 mL, p = 0.006) postoperatively compared with the intravenous group. The tranexamic acid dose was higher in the combined group (5.1 ± 1.1 v 4.1 ± 1.3 g, p0.001), but less was administered intravenously (3.1 ± 1.1 v 4.1 ± 1.3 g, p0.001). No differences were observed in adverse events.This study suggested that combined tranexamic acid administration may be superior for blood conservation, but fully powered randomized controlled trials will be required to confirm these findings and determine the safety advantage and clinical relevance of adding topical tranexamic acid to existing blood conservation strategies.

To determine if central sympathetic blockade by dexmedetomidine, a selective alpha(2) adrenergic receptor agonist, prevents cardiac dysfunction associated with intracranial hypertension (ICH) in a rat model.Following intracisternal administration of dexmedetomidine (1 microg.microL(-1), 10 microL volume) or the stereoisomer levomedetomidine (1 microg.microL(-l), 10 microL volume) in halothane-anesthetized rats, a subdural balloon catheter was inflated for 60 sec to produce ICH. Intracranial pressure, hemodynamic, left ventricular (LV) pressures and electrocardiographic (ECG) changes were recorded. Plasma and myocardial catecholamines and malondialdehyde (MDA) levels were measured.After levomedetomidine administration, subdural balloon inflation precipitated an increase in mean arterial pressure (149 +/- 33% of baseline), heart rate (122 +/- 19% of baseline), LV systolic pressure (LVP), LV end-diastolic pressure (LVEDP), LV developed pressure (LVDP), LV dP/dtmax and rate pressure product (RPP) (132 +/- 19%, 260 +/- 142%, 119 +/- 15%, 126 +/- 24% and 146 +/- 33% of baseline value, respectively). ICH decelerated LVP fall (tau), as tau increased from 7.75 +/- 1.1 to 14.37 +/- 4.5 msec. Moreover, plasma norepinephrine levels were elevated (169 +/- 50% of baseline) and there was the appearance of cardiac dysrhythmias and other ECG abnormalities. This response was transient and cardiac function deteriorated in a temporal manner. Intracisternal dexmedetomidine prevented the rise in plasma norepinephrine, blocked the ECG abnormalities, and preserved cardiac function. Moreover, dexmedetomidine attenuated the rise in MDA levels.The results demonstrate that dexmedetomidine attenuates cardiac dysfunction associated with ICH. Our results provide evidence for the role of central sympathetic hyperactivity in the development of cardiac dysfunction associated with ICH.

UNLABELLED Sympathetic hyperactivity during sudden intracranial hypertension leads to cardiovascular instability, myocardial dysfunction, and neurogenic pulmonary edema. Because spinal anesthesia is associated with sympatholysis, we investigated the protective effects of intrathecal lidocaine in a rodent model. Halothane-anesthetized rats were given a 10-microL intrathecal injection of saline (n = 10) or lidocaine 1% (n = 6). A subdural balloon catheter was inflated for 60 s to produce intracranial hypertension. Hemodynamics were monitored, and hearts and lungs were harvested for histological examination. In Saline versus Lidocaine-Treated rats, peak mean arterial blood pressure during balloon inflation was 115 +/- 4 mm Hg versus 78 +/- 8 mm Hg (P < 0.05), mean arterial blood pressure 30 min after balloon deflation was 47 +/- 2 mm Hg versus 67 +/- 3 mm Hg (P < 0.05), and lung weight was 1.54 +/- 0.03 g versus 1.41 +/- 0.04 g (P < 0.05), respectively. Cardiac dysrhythmias and electrocardiographic changes were more frequent in the Saline-Treated group (P < 0.05). Saline-Treated rats had extensive, hemorrhagic pulmonary edema, whereas the Lidocaine-Treated rats had only patchy areas of lung abnormality. Histological changes in the myocardium were rare, and no difference was found between the two groups. We conclude that intrathecal lidocaine prevents cardiovascular collapse and neurogenic pulmonary edema in a rat model of acute intracranial hypertension. IMPLICATIONS In a rat model of intracranial balloon inflation, intrathecal lidocaine prevented cardiovascular collapse and neurogenic pulmonary edema. Descending neural pathways are involved in the development of cardiopulmonary complications associated with acute intracranial hypertension.

Previous studies have shown that catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) become hyperactive during opioid withdrawal. In the present study, the role of excitatory amino acid pathways in the expression of opioid withdrawal in the RVLM was examined by using differential pulse voltammetry (DNPV) to measure changes in the catecholamine oxidation current (CA.OC) following naloxone challenge in rats treated with acute or chronic morphine. Acute morphine (10 micrograms i.c.v.) significantly reduced the CA.OC signal in the RVLM and the mean arterial pressure to 37.1 +/- 6.6% and 21.1 +/- 3.5% below baseline, respectively. Naloxone (1 mg kg-1 i.v.) reversed the morphine effect and produced a significant increase in the CA.OC signal to 25.6 +/- 15.2% above baseline. In animals treated with chronic morphine (10 micrograms h-1 i.c.v., 5 days), naloxone (1 mg kg-1 i.v.) produced a significant increase in the CA.OC signal to 54.2 +/- 16.5% above baseline. Both the nonselective excitatory amino acid antagonist, gamma-D-glutamylglycine (DGG, 200 micrograms i.c.v.) and the selective NMDA antagonist, D(-)-amino-7-phosphonoheptanoic acid (D-APH, 25 micrograms i.c.v.) attenuated the naloxone-induced increase in the CA.OC by 50.7% and 46.0% respectively. In morphine naive animals, DGG and D-APH depressed the CA.OC by 42.8 +/- 8.7% and 17.7 +/- 9.8%, respectively. To the extent that the CA.OC is an index of neuronal activity, these results suggest that RVLM hyperactivity during morphine withdrawal is dependent, in part, upon activation of NMDA receptors.

METHODS An OR nurse was recruited to function solely as the AA. The AA performed the preoperative nursing checklist, assisted with induction and emergence, and set up anesthesia equipment between cases. There was one week of education and training prior to the start of the 4 week study. Using a prospective, crossover study design, a gynecology OR utilized the AA for 2 weeks while data was simultaneously collected for the control arm in the orthopedic OR. After 2 weeks the AA crossed over to the orthopedic OR and control data was simultaneously collected for the gynecology OR during this time. Demographic and time data were recorded and time differences were analyzed using a Student t-test. General linear modeling was used in multivariable analysis. Alpha less than 0.05 were used for all statistical tests.

Decreased neck extension assessed at the bedside is a predictor of unanticipated difficult intubation. Neck extensions of < 5 cm, in conjunction with the Mallampati airway classification, should become a routine part of airway assessment.