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Prescription opioid abuse during and after pregnancy is a rising public health concern. While earlier studies have documented that offspring exposed to opioids in utero have impaired neurodevelopment, a significant knowledge gap remains in comparing the overall development between offspring exposed in utero and postnatally. Adding a layer of complexity is the role of heredity in the overall development of these exposed offspring. To fill in these important knowledge gaps, the current study uses a preclinical rat model mimicking oxycodone (oxy) exposure in utero (IUO) and postnatally (PNO) to investigate comparative and intergenerational effects in the two different treatment groups. While significant phenotypic attributes were observed with the two treatments and across the two generations, RNA sequencing revealed alterations in the expression of key synaptic genes in the two exposed groups in both generations. RNA sequencing and post validation of genes using RT-PCR highlighted the differential expression of several neuropeptides associated with the hypocretin system, a system recently implicated in addiction. Further, behavior studies revealed anxiety-like behaviors and social deficits that persisted even in the subsequent generations in the two treatment groups. To summarize, our study for the first time reveals a new line of investigation on the potential risks associated with oxy use during and after pregnancy, specifically the disruption of neurodevelopment and intergenerational impact on behavior.

Negative pressure isolation of COVID-19 patients is critical to limiting the nosocomial transmission of SARS-CoV-2; however, airborne isolation rooms are limited. Alternatives to traditional isolation procedures are needed. The evaluation of an Infectious Aerosol Capture Mask (IACM) that is designed to augment the respiratory isolation of COVID-19 patients is described. Efficacy in capturing exhaled breath aerosols was evaluated using laboratory experimentation, computational fluid dynamics (CFD) and measurements of exhaled breath from COVID-19 patients and their surroundings. Laboratory aerosol experiments indicated that the mask captured at least 99% of particles. Simulations of breathing and speaking showed that all particles between 0.1 and 20 µm were captured either on the surface of the mask or in the filter. During coughing, no more than 13% of the smallest particles escaped the mask, while the remaining particles collected on the surfaces or filter. The total exhaled virus concentrations of COVID-positive patients showed a range from undetectable to 1.1 × 106 RNA copies/h of SARS-CoV-2, and no SARS-CoV-2 aerosol was detected in the samples collected that were adjacent to the patient when the mask was being worn. These data indicate that the IACM is useful for containing the exhaled aerosol of infected individuals and can be used to quantify the viral aerosol production rates during respiratory activities.

Cardiorenal syndrome type 2 (CRS2) is defined as a chronic cardiovascular disease, usually chronic heart failure (CHF), resulting in chronic kidney disease. We hypothesized that the cardiac spinal afferent reflex (CSAR) plays a critical role in the development of CRS2. Our data suggest that cardiac afferent ablation by resiniferatoxin not only improves cardiac function but also benefits the kidneys and increases long-term survival in the myocardial infarction model of CHF. We also found that renal denervation has a similar reno-protective effect in CHF rats. We believe this novel work contributes to the development of a unique neuromodulation therapy to treat CHF patients.

Acute lung injury (ALI) is characterized by the abrupt onset of clinically significant hypoxemia in the context of non-hydrostatic pulmonary edema. Acute lung injury is associated with cytokine release and plasma extravasation (PEx) that can cause pulmonary edema and subsequently acute respiratory distress syndrome (ARDS). Therefore, it is critical we understand the relationship between ALI and lung PEx. In addition, it is also important to assess PEx in the lungs and other organs post-ALI since ALI/ARDS often causes multi-organ failure. We hypothesized that ALI induces time-dependent lung PEx, which promotes extravasation in the heart, liver, kidney, spleen, pancreas, and gastrointestinal (GI) tract, in a time-dependent manner. To test our hypothesis, we administered bleomycin or saline via tracheal intubation in 8-week-old Sprague Dawley rats. At the terminal experiments, Evans Blue was injected (IV) through the femoral vein to allow for the visualization of PEx. Plasma extravasation of desired organs was evaluated at 3-, 7-, 14-, 21-, and 28-days after bleomycin or saline treatment by evaluating Evans Blue concentrations calorimetrically at fluorescence excitation wavelength of 620 nm (bandwidth 10 nm) and an emission wavelength of 680 nm (bandwidth 40 nm). Data show that ALI induces lung PEx beginning at day 3 and peaking between 7 and 21 days. Extravasation was also seen in all organs at varying degrees beginning at day 3 and peaking between days 7 and 14. Resolution appears to start after day 21 and continues past day 28. We conclude that ALI caused by bleomycin incites a time-dependent PEx of the lungs and multiple other organs.

Introduction: A systematic analysis of clinical trials was performed in order to assess the effectiveness and risks of bilateral renal denervation (RDN) in patients with chronic heart failure with reduced ejection fraction (HFrEF). Methods: A systematic review was conducted of all clinical trials exploring the effectiveness of RDN in patients with HF who had reduced (

Aim Patients suffering from acute lung injury (ALI) are at high risk of developing cardiac arrhythmias. We hypothesized that stellate ganglia (SG) neural inflammation contributes to ALI-induced arrhythmia. Methods We created an ALI rat model using a single tracheal instillation of bleomycin (2.5 mg/kg), with saline as a sham control. We recorded ECGs by implanted radiotelemetry in male bleomycin and sham rats treated with and without oral minocycline (20 mg/kg/d), an anti-inflammatory drug that inhibits microglia/macrophage activation. The SG neuronal excitability was assessed by electrophysiology experiments. Results ECG data showed that bleomycin-exposed rats exhibited significantly more spontaneous premature ventricular contractions (PVCs) from 1- to 3-week post-induction compared with sham rats, which was mitigated by chronic oral administration of minocycline. The bleomycin-exposed rats displayed a robust increase in both the number of Iba1-positive macrophages and protein expression of interferon regulatory factor 8 in the SG starting as early at 1-week post-exposure and lasted for at least 4 weeks, which was largely attenuated by minocycline. Heart rate variability analysis indicated autonomic imbalance during the first 2-week post-bleomycin, which was significantly attenuated by minocycline. Electrical stimulation of the decentralized SG triggered more PVCs in bleomycin-exposed rats than sham and bleomycin + minocycline rats. Patch-clamp data demonstrated enhanced SG neuronal excitability in the bleomycin-exposed rats, which was attenuated by minocycline. Co-culture of lipopolysaccharide (LPS)-pretreated macrophages with normal SG neurons enhanced SG neuronal excitability. Conclusion Macrophage activation in the SG contributes to arrhythmogenesis in bleomycin-induced ALI in male rats.

Background We previously derived a Universal Vital Assessment (UVA) score to better risk-stratify hospitalized patients in sub-Saharan Africa, including those with infection. Here, we aimed to externally validate the performance of the UVA score using previously collected data from patients hospitalized with acute infection in Rwanda. Methods We performed a secondary analysis of data collected from adults ≥18 years with acute infection admitted to Gitwe District Hospital in Rwanda from 2016 until 2017. We calculated the UVA score from the time of admission and at 72 hours after admission. We also calculated quick sepsis-related organ failure assessment (qSOFA) and modified early warning scores (MEWS). We calculated amalgamated qSOFA scores by inserting UVA cut-offs into the qSOFA score, and modified UVA scores by removing the HIV criterion. The performance of each score determined by the area under the receiver operator characteristic curve (AUC) was the primary outcome measure. Results We included 573 hospitalized adult patients with acute infection of whom 40 (7%) died in-hospital. The admission AUCs (95% confidence interval [CI]) for the prediction of mortality by the scores were: UVA, 0.77 (0.68–0.85); modified UVA, 0.77 (0.68–0.85); qSOFA, 0.66 (0.56–0.75), amalgamated qSOFA, 0.71 (0.61–0.80); and MEWS, 0.74 (0.64, 0.83). The positive predictive values (95% CI) of the scores at commonly used cut-offs were: UVA >4, 0.35 (0.15–0.59); modified UVA >4, 0.35 (0.15–0.59); qSOFA >1, 0.14 (0.07–0.24); amalgamated qSOFA >1, 0.44 (0.20–0.70); and MEWS >5, 0.14 (0.08–0.22). The 72 hour (N = 236) AUC (95% CI) for the prediction of mortality by UVA was 0.59 (0.43–0.74). The Chi-Square test for linear trend did not identify an association between mortality and delta UVA score at 72 hours (p = 0.82). Conclusions The admission UVA score and amalgamated qSOFA score had good predictive ability for mortality in adult patients admitted to hospital with acute infection in Rwanda. The UVA score could be used to assist with triage decisions and clinical interventions, for baseline risk stratification in clinical studies, and in a clinical definition of sepsis in Africa.

Background: Increased risk of oxycodone (oxy) dependency during pregnancy has been associated with altered behaviors and cognitive deficits in exposed offspring. However, a significant knowledge gap remains regarding the effect of in utero and postnatal exposure on neurodevelopment and subsequent behavioral outcomes.Methods: Using a preclinical rodent model that mimics oxy exposure in utero (IUO) and postnatally (PNO), we employed an integrative holistic systems biology approach encompassing proton magnetic resonance spectroscopy (1H-MRS), electrophysiology, RNA-sequencing, and Von Frey pain testing to elucidate molecular and behavioral changes in the exposed offspring during early neurodevelopment as well as adulthood.Results:1H-MRS studies revealed significant changes in key brain metabolites in the exposed offspring that were corroborated with changes in synaptic currents. Transcriptomic analysis employing RNA-sequencing identified alterations in the expression of pivotal genes associated with synaptic transmission, neurodevelopment, mood disorders, and addiction in the treatment groups. Furthermore, Von Frey analysis revealed lower pain thresholds in both exposed groups.Conclusions: Given the increased use of opiates, understanding the persistent developmental effects of these drugs on children will delineate potential risks associated with opiate use beyond the direct effects in pregnant women.

HIGHLIGHTS • Providers are at risk for contracting COVID-19 due to close patient contact • Proper personal protective equipment use is critical to providing a safe environment • Face shields are an alternative for enhancing protection given the shortage of N95 • We present the detailed protocol for printing 3D face shields in a timely manner • This protocol is aimed to individuals with little to no 3D printing experience, Anesthesia providers are at risk for contracting COVID-19 due close patient contact. Proper personal protective equipment (PPE) use is critical to providing a safe environment and to minimize the risk of contagion. During the COVID-19 Pandemic, a series of supply chain issues, constant changes in PPE use policy, and higher demand for PPE led to shortages in PPE, specifically N95 masks and face shields. Implementation of decontamination protocols successfully allowed N95 mask reuse but, required masks to be unsoiled. Face shields not only act as a barrier against the soiling of N95 face masks, they also serve as more effective eye protection from respiratory droplets over standard eye shields. The University of Nebraska Medical Center produced face shields using a combination of 3D printing and assembly with commonly available products. Approximately 112 face shields were constructed and made available for use in 72 hours. Importantly, we created and implemented a simple but effective decontamination protocol, which allowed reuse of the face shields. These methods were successfully implemented for in-house production of face shields used at Tripler Army Medical Center (Tripler AMC, Hawaii). The effectiveness of the decontamination protocol was evaluated using the average log10 reduction in colony counts for Escherichia coli ATCC 8937 and Staphylococcus aureus ATCC 25923 from the American Type Culture Collection (ATCC, Manassas, VA). In this manuscript, we present our detailed protocol and supplies needed for printing 3D face shields to enable the rapid production of this product by individuals with little to no 3D printing experience, in times of urgent need.

BACKGROUND The release of damage-associated molecular pattern molecules in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that would be associated with poor outcomes. METHODS We conducted a prospective observational study of 149 pediatric trauma patients and 62 control patients at two level 1 pediatric trauma centers from 2013 to 2016. Blood samples were collected upon arrival and at 24 h, analyzed for hcDNA, coagulation abnormalities, endothelial damage, and clinical outcome. Platelet aggregation was assessed with impedance aggregometry (Multiplate) and coagulation parameters were assessed by measuring prothrombin time ratio in plasma and the use of viscoelastic techniques (Rotational Thromboelastometry) in whole blood. RESULTS The median age was 8.3 years, the median injury severity score (ISS) was 20, and overall mortality was 10%. Significantly higher levels of hcDNA were found on admission in patients with severe injury (ISS > 25), coagulopathy, and/or abnormal platelet aggregation. Patients with high hcDNA levels also had significant elevations in plasma levels of syndecan-1, suggesting damage to the endothelial glycocalyx. Finally, significantly higher hcDNA levels were found in non-survivors. CONCLUSION hcDNA is released following injury and correlates with coagulopathy, endothelial glycocalyx damage, and poor clinical outcome early after severe pediatric trauma. These results indicate that hcDNA may play an important role in development of coagulation abnormalities and endothelial glycocalyx damage in children following trauma.

Background The critically ill or injured patient undergoing military medical evacuation may require emergent intubation. Intubation may be life-saving, but it carries risks. The novice or infrequent laryngoscopist has a distinct disadvantage because experience is critical for the rapid and safe establishment of a secured airway. This challenge is compounded by the austere environment of the back of an aircraft under blackout conditions. This study determined which of five different video-assisted intubation devices (VAIDs) was best suited for in-flight use by U.S. Air Force Critical Care Air Transport Teams by comparing time to successful intubation between novice and expert laryngoscopists under three conditions, Normal Airway Lights on (NAL), Difficult Airway Lights on (DAL) and Difficult Airway Blackout (DAB), using manikins on a standard military transport stanchion and the floor with a minimal amount of setup time and extraneous light emission. Methods A convenience sample size of 40 participants (24 novices and 16 experts) attempted intubation with each of the 5 different video laryngoscopic devices on high-fidelity airway manikins. Time to tracheal intubation and number of optimization maneuvers used were recorded. Kruskal-Wallis testing determined significant differences between the VAIDs in time to intubation for each particular scenario. Devices with significant differences underwent pair-wise comparison testing using rank-sum analysis to further clarify the difference. Device assembly times, startup times and the amount of light emitted were recorded. Perceived ease of use was surveyed. Results Novices were fastest with the Pentax AWS in all difficult airway scenarios. Experts recorded the shortest median times consistently using 3 of the 5 devices. The AWS was superior overall in 4 of the 6 scenarios tested. Experts and novices subjectively judged the GlideScope Ranger as easiest to use. The light emitted by all the devices was less than the USAF-issued headlamp. Conclusions Novices intubated fastest with the Pentax AWS in all difficult airway scenarios. The GlideScope required the shortest setup time, and participants judged this device as the easiest to use. The GlideScope and AWS exhibited the two fastest total setup times. Both devices are suitable for in-flight use by infrequent and seasoned laryngoscopists.

Oxycodone (oxy) is a semi-synthetic opioid commonly used as a pain medication that is also a widely abused prescription drug. While very limited studies have examined the effect of in utero oxy (IUO) exposure on neurodevelopment, a significant gap in knowledge is the effect of IUO compared with postnatal oxy (PNO) exposure on synaptogenesis&mdash, a key process in the formation of synapses during brain development&mdash, in the exposed offspring. One relatively unexplored form of cell&ndash, cell communication associated with brain development in response to IUO and PNO exposure are extracellular vesicles (EVs). EVs are membrane-bound vesicles that serve as carriers of cargo, such as microRNAs (miRNAs). Using RNA-Seq analysis, we identified distinct brain-derived extracellular vesicle (BDEs) miRNA signatures associated with IUO and PNO exposure, including their gene targets, regulating key functional pathways associated with brain development to be more impacted in the IUO offspring. Further treatment of primary 14-day in vitro (DIV) neurons with IUO BDEs caused a significant reduction in spine density compared to treatment with BDEs from PNO and saline groups. In summary, our studies identified for the first time, key BDE miRNA signatures in IUO- and PNO-exposed offspring, which could impact their brain development as well as synaptic function.

Background: People who suffer lung injury, incurred through a variety of means, are at greatly increased risk of developing cardiac arrhythmias. Treatment options remain limited. We propose that stellate ganglia neuro-inflammation contributes to lung injury-induced arrhythmogenesis. Methods: We created lung injury in adult Sprague-Dawley rats by a single tracheal instillation of Bleomycin (Bleo, 2.5 mg/kg), and used Saline instillation as a control. We recorded ECGs in conscience, freely moving Bleo and Saline rats treated with and without oral minocycline (20 mg/kg/day for 4 weeks, an anti-inflammatory drug to inhibit microglia/macrophage activation) using implantable radio-telemeters. During terminal experimentation we investigated the effect of minocycline on isolated electrical stellate stimulation-induced cardiac arrhythmias in Bleo rats. Results: Bleo rats exhibited lung lesions at necropsy and lung fibrosis histologically. Bleo rats, on average, had more premature ventricular contractions (PVCs) than Saline rats, an effect largely prevented by chronic treatment with minocycline. (PVC data 1-wk post Bleo: Saline 22±12, Bleo 481±394*#, Bleo+Mino 24±9. PVC data 2-wks post Bleo: Saline 6±2, Bleo 255±165*, Bleo+Mino 21±8. Data are AVG±SEM number of PVCs over 24-hr, n=5-6 for all groups. *P Conclusion: Our data showed that stellate ganglia neuroinflammation contributes to arrhythmogenesis in our Bleo lung injury rat model.

Excessive sympathoexcitation characterizes the chronic heart failure (CHF) state. An exaggerated cardiac sympathetic afferent reflex (CSAR) contributes to this sympathoexcitation. Prior studies have demonstrated that the CSAR to capsaicin [transient receptor potential (TRP) vanilloid 1 agonist] is exaggerated in CHF animal models. We recently discovered that capsaicin application to the lung visceral pleura in anesthetized, vagotomized, open-chested rats increases mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). We named this response the pulmonary spinal afferent reflex (PSAR). Due to the similarities between TRP vanilloid 1 and TRP ankyrin 1 (TRPA1) channels as well as the excessive sympathoexcitation of CHF, we hypothesized that stimulation of the CSAR and PSAR with a specific TRPA1 agonist would result in an augmented response in CHF rats (coronary ligation model) compared with sham control rats. In response to a TRPA1 agonist, both CSAR and PSAR in sham rats resulted in biphasic changes in MAP and increases in HR and RSNA 10–12 wk postmyocardial infarction (post-MI). These effects were blunted in CHF rats. Assessment of TRPA1 expression levels in cardiopulmonary spinal afferents by immunofluorescence, quantitative RT-PCR, and Western blot analysis 10–12 wk post-MI all indicates reduced expression in CHF rats but no reduction at earlier time points. TRPA1 protein was reduced in a dorsal root ganglia cell culture model of inflammation and simulated tissue ischemia, raising the possibility that the in vivo reduction of TRPA1 expression was, in part, caused by CHF-related tissue ischemia and inflammation. These data provide evidence that reflex responses to cardiopulmonary spinal afferent TRPA1 stimulation may be attenuated in CHF rather than enhanced.NEW & NOTEWORTHY Excessive sympathoexcitation characterizes chronic heart failure (CHF). The contribution of transient receptor potential ankyrin 1 (TRPA1) channel-mediated reflexes to this sympathoexcitation is unknown. We found that application of TRPA1 agonist to the heart and lung surface resulted in increased heart rate and sympathetic output and a biphasic change in mean arterial pressure in control rats. These effects were attenuated in CHF rats, decreasing the likelihood that TRPA1 channels contribute to cardiopulmonary afferent sensitization in CHF.

Background Substance Abuse is very high among anesthesiologists. Recent data have shown that 32% of anesthesiologists have used drugs to “get high,” while 16% have stated they were drug dependent. Anesthesiologists have a 2.5 times higher rate of drug abuse than the average physician. Multiple factors play a role in explaining the high incidence of substance abuse among anesthesiologists. Proximity to large quantities of highly addictive drugs, relative ease at diverting small quantities of drugs, and a high stress environment all play a role. Additionally, a workplace that sensitizes reward pathways and promotes substance abuse also contributes. Methods We tracked narcotic discrepancies for seven years, from 2013 through 2019. We received the total number of narcotic discrepancies from data through the hospital reporting system. In the span of the seven years, multiple process changes were put into place to reduce the number of narcotic discrepancies. In 2015, the Omnicell automatic drug delivery system was placed into each operating room (OR). This offered both customized access to narcotics throughout a surgical procedure and clear documentation of quantities of narcotics taken out for each patient. In 2016, pharmacy started e-mailing anesthesia providers if their narcotic documentation was not accurate. This added a second check to narcotic quantities and brought about the most dramatic decrease in discrepancies. The last process we added was a narcotic hand off tool in the electronic medical record. This tool documents narcotic quantities being handed off to another anesthesia provider during staffing changes. Results No single process change resulted in complete resolution of all narcotic discrepancies. When the pharmacy started to give feedback on the narcotic discrepancies, the total number of discrepancies decreased dramatically by 85%. The addition of the “hand-off tool” also reduced the number by an additional 35%. Conclusion We found when there are multiple system and personnel checks, the number of narcotic discrepancies decreased more than just one system or check in place.

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague-Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1-expressing afferent soma at the level of T1-T4 dorsal root ganglia pleura. This treatment abolished all sympatho-excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9-10 weeks post-RTX. These data suggest the presence of an excitatory pulmonary chemosensitive sympathetic afferent reflex. This finding may have important clinical implications in pulmonary conditions inducing sensory nerve activation such as pulmonary inflammation and inhalation of chemical stimuli.

Objective This report will describe the preparations for and the provision of care of two patients with Ebola virus disease in the biocontainment unit at the University of Nebraska Medical Center. Data sources Patient medical records. Study selection Not applicable. Data extraction Not applicable. Data synthesis Not applicable. Conclusions Safe and effective care of patients with Ebola virus disease requires significant communication and planning. Adherence to a predetermined isolation protocol is essential, including proper donning and doffing of personal protective equipment. Location of the patient care area and the logistics of laboratory testing, diagnostic imaging, and the removal of waste must be considered. Patients with Ebola virus disease are often dehydrated and need adequate vascular access for fluid resuscitation, nutrition, and phlebotomy for laboratory sampling. Advanced planning for acute life-threatening events and code status must be considered. Intensivist scheduling should account for the significant amount of time required for the care of patients with Ebola virus disease. With appropriate precautions and resources, designated hospitals in the United States can safely provide care for patients with Ebola virus disease.

Recently, we reported activation of pulmonary spinal afferents by topical application of bradykinin (BK) to lung surfaces evokes a potent sympatho-excitatory reflex, including increased blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in urethane-α-chloralose anesthetized vagotomized rats. This finding suggests a new previously undocumented pulmonary sympathetic afferent reflex (PSAR). Preliminary data was reported in abstract form at the Association of University Anesthesiologists 64 th Annual meeting. Expanding this work, we examined the activation of the PSAR at different time points post myocardial infarction (1 month vs. 5 months post MI) and at different degrees of infarct size (15%-35% (moderate) vs. above 35% (large) of left ventricle). Following bilateral vagotomy , we applied filter paper (3 х 3 mm) saturated with BK (10 μg/ml) to the ventral lung surface to stimulate the PSAR in both urethane- α-chloralose anesthetized sham-operated and MI rats. Application of BK to the lungs resulted in increased BP, HR and RSNA in all sham and MI rats. Compared to sham rats, the BK-induced sympatho-excitatory response was significantly increased in 1-month moderate and 1-month large MI rats as well as in 5-month moderate MI rats. The BK-induced sympatho-excitatory response was significantly blunted in 5-month large MI rats (Table 1). These data suggest that the activation of pulmonary spinal afferents in the post-MI state may be an independent risk factor for sympatho-excitation. Further studies are needed to understand the differential effects of pulmonary spinal afferent activation at the transition from the post MI state to heart failure.

We describe a preoperative transthoracic echocardiography consult service led by anesthesiologists. The implementation process and the patient cohort are described. Preoperative transthoracic echocardiographic examinations were mostly performed in patients undergoing intermediate- or high-risk noncardiac surgery and in patients with a higher calculated mortality risk. All transthoracic echocardiographic examinations were interpreted by anesthesiologists.

Trauma remains the leading cause of morbidity and mortality in the United States among children aged 1 to 21 years. The most common cause of lethality in pediatric trauma is traumatic brain injury. Early coagulopathy has been commonly observed after severe trauma and is usually associated with severe hemorrhage and/or traumatic brain injury. In contrast to adult patients, massive bleeding is less common after pediatric trauma. The classical drivers of trauma-induced coagulopathy include hypothermia, acidosis, hemodilution, and consumption of coagulation factors secondary to local activation of the coagulation system after severe traumatic injury. Furthermore, there is also recent evidence for a distinct mechanism of trauma-induced coagulopathy that involves the activation of the anticoagulant protein C pathway. Whether this new mechanism of posttraumatic coagulopathy plays a role in children is still unknown. The goal of this review is to summarize the current knowledge on the incidence and potential mechanisms of coagulopathy after pediatric trauma and the role of rapid diagnostic tests for early identification of coagulopathy. Finally, we discuss different options for treating coagulopathy after severe pediatric trauma.

Background Uncertainty exists about a safe dose limit to minimize radiation-induced cancer. Maximum occupational exposure is 20 mSv/y averaged over 5 years with no more than 50 mSv in any single year. Radiation exposure to the general population is less, but the average dose in the United States has doubled in the past 30 years, largely from medical radiation exposure. We hypothesized that patients in a mixed-use surgical ICU (SICU) approach or exceed this limit and that trauma patients were more likely to exceed 50 mSv because of frequent diagnostic imaging. Methods Patients admitted into 15 predesignated SICU beds in a level I trauma center during a 30-day consecutive period were prospectively observed. Effective dose was determined using Huda's method for all radiography, CT imaging, and fluoroscopic examinations. Univariate and multivariable linear regressions were used to analyze the relationships between observed values and outcomes. Results Five of 74 patients (6.8%) exceeded exposures of 50 mSv. Univariate analysis showed trauma designation, length of stay, number of CT scans, fluoroscopy minutes, and number of general radiographs were all associated with increased doses, leading to exceeding occupational exposure limits. In a multivariable analysis, only the number of CT scans and fluoroscopy minutes remained significantly associated with increased whole-body radiation dose. Conclusions Radiation levels frequently exceeded occupational exposure standards. CT imaging contributed the most exposure. Health-care providers must practice efficient stewardship of radiologic imaging in all critically ill and injured patients. Diagnostic benefit must always be weighed against the risk of cumulative radiation dose.

Early goal-directed therapy has shown discordant survival outcomes in sepsis studies. We aim to find the reasons for this discordance.Random-effects and Bayesian hierarchical analyses.Studies that evaluated early goal-directed therapy.Patients with severe sepsis and/or septic shock.Early goal-directed therapy.A total of 19,998 patients were included in the main analysis: 31 observational (n = 15,656) and six randomized (n = 4,342) studies. The analysis from 37 studies showed that early goal-directed therapy was associated with a 23% reduction in the risk of death: relative risk = 0.77 (95% CI, 0.71-0.83); p value of less than 0.0001. Mortality reduction was seen with observational studies: relative risk = 0.73 (0.67-0.80); p value of less than 0.0001 but not with randomized studies: relative risk = 0.92 (0.78-1.07); p = 0.268. Meta-regression analysis showed lower risk of death in observational compared with randomized studies: relative risk = 0.81 (0.68-0.95); p = 0.01. Differences in age, country, hospital location, era, systolic pressure, mean arterial pressure, lactate, bundle compliance, amount of fluid administered, and hemodynamic goal achievements were not associated with survival differences between studies. Factors associated with mortality differences between early goal-directed therapy and control included Acute Physiology and Chronic Health Evaluation II (relative risk = 1.05 [1.02-1.09]; p = 0.003), Sequential Organ Failure Assessment (relative risk = 1.09 [1.00-1.18]; p = 0.04), presence of shock (relative risk = 1.007 [1.002-1.013]; p = 0.006), time-to-first antibiotic (relative risk = 1.22 [1.09-1.36]; p = 0.0006), antibiotic administration within 6 hours (relative risk = 0.20 [0.09-0.45]; p = 0.0001), 4 hours (relative risk = 0.16 [0.06-0.39]; p = 0.0001), and 3 hours (relative risk = 0.09 [0.03-0.27]; p0.0001). The only factors that explained mortality differences between randomized and observational studies were time-to-first antibiotic (R = 87%), antibiotic administration within 6 hours (R = 94%), 4 hours (R = 99%), 3 hours (R = 99%), and appropriate antibiotic use (R = 96%).Survival discordance was not associated with differences in early goal-directed therapy bundle compliance or hemodynamic goal achievement. Our results suggest that it was associated with faster and more appropriate antibiotic co-intervention in the early goal-directed therapy arm compared with controls in the observational studies but not in the randomized trials. Early goal-directed therapy was associated with increased mortality in patients with high-disease severity.

Background There are limited data regarding emergent, non-operating room, intubations performed by all levels of anesthesia residents. This study was a large retrospective review of all non-operating room emergent intubations performed at a single tertiary medical center. The study evaluated the rate of difficult intubations by level of resident training, compared success rates for direct versus video laryngoscopy and evaluated the rate and success of rescue video laryngoscopy following failed direct laryngoscopy. Methods All emergent non-operating room intubations at a tertiary university medical center from July 1, 2009, to August 1, 2012, were reviewed and all study data were collected from the medical records. Intubations were classified as being initiated with either direct or video methods. The total number of attempts required and the rate of success were compared by resident year and intubation type. Results Out of a total of 788 emergent intubations, 741 were performed by anesthesia residents. The higher level anesthesia residents (CA-2 and CA-3) had a statistically significant decrease in the number of attempts needed when compared to CA-1 residents. Rate of success did not vary by resident training year, but success rates were higher for cases initiated with video laryngoscopy. Among direct initiated cases, 8% failed initial direct laryngoscopy and were then successfully intubated with rescue video laryngoscopy. Conclusions During emergent, non-operating room intubations, senior level residents used fewer attempts at intubations with direct laryngoscopy. Successful intubation was improved by beginning residents when video laryngoscopy was utilized. Complications were not affected by the presence of the attending anesthesiologist.

STATEMENT The recent Ebola outbreak brought to bear the true nature of our ever-shrinking global health care community. Geography can no longer be considered a barrier to the spread of a highly communicable disease. Health care providers must be prepared to care for these patients regardless of location or environment. The simulation community responded rapidly to the Ebola epidemic with creative and timely solutions for training and systems optimization. Successful programs focused on 2 primary aims. First, the programs equipped the health care workers with essential knowledge for caring for their patients and protecting themselves. Second, they provided feedback to the system itself, identifying gaps in protocol and solutions for logistic challenges these patients often present. By having simulation integrated into the patient safety culture of our health care systems, we set in place a powerful tool that can respond nimbly to a high-stakes threat as evidenced by the success of these Ebola programs.

The abuse of opiates such as morphine in synergy with HIV infection not only exacerbates neuropathogenesis but significantly impacts behavioral attributes in HIV infected subjects. Thus, the goal of the current study was to characterize behavioral perturbations in rhesus macaques subjected to chronic morphine and SIV infection. Specifically, we assessed three behavioral tasks: motor skill (MS), forelimb force (FFT) and progressive ratio (PR) tasks. After collecting baseline control data (44 weeks) and data during the morphine-only dependency period (26 weeks), a subset of animals were productively infected with neurovirulent strains of SIVmac (R71/E17) for an additional 33 weeks. A general pattern in the results is that behavioral decline occurred with high CSF viral loads but not necessarily with high plasma viral loads. Compared to saline controls, all treated animals showed significant decreases in performance on all three behavioral tasks during the morphine-only dependency period. During the post infection period, only the morphine plus SIV group showed a significant further decline and this only occurred for the MS task. Taken together, these data demonstrate a clear effect of morphine to produce behavioral deficits and also suggest that morphine can act synergistically with SIV/HIV to exacerbate behavioral deficits.

IntroductionPostoperative pulmonary complications (PPCs) frequently result in serious morbidity and mortality. Although the evaluation and management of pulmonary patients undergoing thoracic surgery has received much attention in the literature, risk stratification and perioperative management of p

Ebola virus disease (EVD) is a severe illness primarily characterized by fever, fatigue, diarrhea, and vomiting. It was first identified in 1976 with several small, limited outbreaks occurring between 1976 and 2012 (1, 2). Since December 2013, a complex and wide-ranging outbreak of EVD centered in West Africa has primarily affected Guinea, Liberia, and Sierra Leone. As of March 11, 2015, the current outbreak has resulted in approximately 24,282 confirmed and suspected cases with 9,976 deaths globally (3). For the first time in history, there has been both local and distant spread of EVD in West Africa—to neighboring nations (including Mali, Nigeria, and Senegal)—and to resource-rich nations in Europe and North America through multiple mechanisms, including repatriation of infected healthcare workers (HCW), index cases traveling to resource-rich nations, and local spread through contacts with infected HCW (4). Limited laboratory and other resources in the affected West African nations have hampered a more detailed understanding of the clinical phenotypes of EVD. Several recently published case series demonstrate that there is a wide spectrum of severity of illness in EVD ranging from mild-to-moderate symptoms largely confined to the gastrointestinal system (copious watery diarrhea, vomiting, abdominal pain, and acute hepatitis) to the development of organ failure and death (5–7). Reported mortality rates in West Africa during the current outbreak have ranged from 40% to 70%, which is notably improved from previous outbreaks where mortality rates approached 90% (3, 8). With the arrival of EVD to resource-rich nations, a more detailed description of the natural history of both mild and severe EVD is beginning to emerge with several patients in the United States and Europe developing critical illness requiring advanced life support with mechanical ventilation and renal replacement therapy (RRT) (9–12). As in previous outbreaks, both severity of illness and mortality risk appear to be associated with both viral load at presentation and peak viral load (5, 13). Here, we report the spectrum of critical illness, organ failure, laboratory data, and interventions on three patients with severe EVD in the United States.

Objective The primary aim of the study was to describe the most common intraoperative transesophageal echocardiography (TEE) findings during the 3 separate phases of orthotopic liver transplantation (OLT). The secondary aim of the study was to determine if the abnormal TEE findings were associated with major postoperative adverse cardiac events (MACE) and thus may be amenable to future management strategies. Design Data were collected retrospectively from the electronic medical record and institutional echocardiography database. Setting Single university hospital. Participants A total of 100 patients undergoing OLT via total cavaplasty technique. Interventions Intraoperative TEE was performed in all 3 phases of OLT. Measurement and Main Results TEE findings of 100 patients who had TEE during OLT during the dissection, anhepatic, and reperfusion phases of transplantation were recorded after blind review. Findings then were analyzed to see if those findings were predictive of postoperative MACE. Intraoperative TEE findings varied among the different phases of OLT. Common TEE findings at reperfusion were microemboli (n = 40, 40%), isolated right ventricular dysfunction (n = 22, 22%), and intracardiac thromboemboli (n = 20, 20%). Conclusions Intraoperative echocardiography findings during liver transplantation varied during each phase of transplantation. The presence of intracardiac thromboemboli or biventricular dysfunction on intraoperative echocardiography was predictive of short- and long-term major postoperative adverse cardiac events.

Study Objective The purpose of this study was to assess the workflow interruptions on an anesthesiology clinical director (CD). By assessing the interruptions on the CD, we hypothesize that these frequent interruptions would prohibit the CD from medical direction of residents or certified nurse anesthetists in operating rooms. Design Cellular phone data were obtained from Verizon Wireless statements over 10 months, August 2012 through May 2013. These data were from a single cellular phone carried by the anesthesia CD and subsequent overnight anesthesiologist 24 hours a day. The data obtained from the billing records included number of calls, date and time call occurred, number of minutes per call, and number of texts received. Setting These calls occurred in the operating room. Patients Not applicable. Intervention Not applicable. Measurements Phone calls, texts, and pager interruptions. Main Results A total of 19,924 calls and 19,803 texts were received by the CD. The phone calls minutes for this period were 31,236 minutes. A total of 15,831 (80%) of the calls occurred during this period (0600-1800). A total of 24 489 minutes (78%) of the total minutes occurred during this time. Conclusion This study revealed that distracting events are frequent for an anesthesiology CD. The quantity of cellular phone interruptions, both calls and texts, by the anesthesiology CD was considered high. These calls occurred mainly during prime operating room time and utilization. As the CD is an integral part of the perioperative management team, they are expected to answer and return calls and texts promptly. Operating room efficiency and staff satisfaction decline if responses to these calls and texts are delayed. Although the nature of these distractions and interruptions can be viewed as having a positive or negative effect, many of these events are necessary to efficiently run the operating rooms.

The abuse of opiates such as morphine in synergy with HIV infection accelerates neurocognitive impairments and neuropathology in the CNS of HIV-infected subjects, collectively referred to as HAND. To identify potential pathogenic markers associated with HIV and morphine in perturbing the synaptic architecture, we performed quantitative mass spectrometry proteomics on purified synaptosomes isolated from the caudate of two groups of rhesus macaques chronically infected with SIV differing by one regimen—morphine treatment. The upregulation of heat shock 70-kDa protein 5 in the SIV + morphine group points to increased cellular stress during SIV/morphine interaction thus leading to CNS dysfunction.

Procedural sedation is essential for many procedures. Sedation has an excellent safety profile; however, it is not without risks. Assessment of risk using clinical outcomes in clinical studies is difficult due to their rare occurrence. Therefore, surrogate end points are frequently used in a clinical study in lieu of clinical outcomes. As a clinician integrates multiple aspects of a physiological variable to determine potential risk, a surrogate end point should consider a similar approach. In this study, we identified and tested the appropriateness of a new surrogate end point that may be used in clinical studies, area under the curve of oxygen desaturation (AUCDesat). A review of patient sedation records by anesthesiologists was conducted to assess its relationship to the anesthesia professional perception of risk.This study was a post hoc analysis and assessment of perceived risk by anesthesiologists. It consisted of 13 U.S.-trained board-certified anesthesiologists ranking physiological variables as indicators of risk and then reviewing 204 records from 3 completed sedation studies involving the SEDASYS System. After review, each anesthesiologist assigned a Likert score based on his or her perception of risk for oversedation-related sequelae in each record. These scores were analyzed to determine their relationship to desaturation presence/absence, duration, depth, number of events, and AUCDesat that incorporates each component.Anesthesiologists ranked arterial oxygenation to be the most important factor in assessing risk post hoc (mean rank of 4.69 of 5, P = 0.0007 compared with next highest ranked factor-respiratory rate, N = 13). AUCDesat was better correlated to the Likert scores (rs = 0.85) when compared with the individual elements of AUCDesat, binary assessment of desaturation (rs = 0.73), desaturation depth (rs = -0.70), desaturation duration (rs = 0.70), and incidence of desaturations (rs = 0.55) (all 4 comparisons versus rs = 0.85, P0.0001).Anesthesiologists determined arterial oxygenation to be the most important physiological variable in assessing sedation risk and the potential for adverse clinical outcomes. AUCDesat, a composite index that incorporates duration, incidence, and depth of oxygen desaturation, was better correlated to the Likert scores. AUCDesat, given that it is a single numerical variable, is an ideal end point for assessment of risk of adverse clinical outcomes in clinical sedation studies. Future studies using AUCDesat and actual physiological outcomes may be useful in further defining this end point.

From the *Department of Anesthesiology; and †Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska. The administrative development of a perioperative echocardiography consult service at the University of Nebraska Medical Center was supported by the 2012 Society of Cardiovascular Anesthesiologists Foundation Kaplan Leadership Grant. Address reprint requests to Sasha K. Shillcutt, MD, FASE, 984455 Nebraska Medical Center, Omaha, NE 68198-4455. E-mail: sshillcu@ unmc.edu © 2015 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.09.010

The growth of managed care continues to impact American health care in a variety of ways. Two significant changes that have resulted from managed care strategies include a dramatic emphasis on primary care, and reorganization of inpatient care, which is provided by hospital-based clinicians. These hospital-based models are being adopted by an increasing number of both teaching and nonteaching institutions from New England to California. What role will the anesthesiologist play in this new era? Will our practice be limited to that of intraoperative providers of anesthesia or will we assume greater responsibility and take a leadership role in directing the evolution of a system striving for efficient, cost-effective delivery of medical, surgical, and perioperative care? The trend toward generalism has already had an impact on anesthesiology—visible by its effect on the preference of American medical school graduates, with a significant falloff in the number of students choosing specialty (especially anesthesiology) residencies. This chapter will explore the hospitalist movement and discuss the possible role of anesthesiologists as they expand their practice as perioperative specialists.

Background Non-physician advanced practice providers (APPs) such as nurse practitioners and physician assistants are being increasingly utilized as critical care providers in the United States. The objectives of this study were to determine the utilization of APPs in the intensive care units (ICU)s of academic medical centers (AMCs) and to assess the perceptions of critical care fellowship program directors (PDs) regarding the impact of these APPs on fellowship training. Methods A cross-sectional national survey questionnaire was distributed to program directors of 331 adult Accreditation Council for Graduate Medical Education-approved critical care fellowship training programs (internal medicine, anesthesiology and surgery) in US AMCs. Results We received 124 (37.5%) PD responses. Of these, 81 (65%) respondents indicated that an APP was part of the care team in either the primary ICU or any ICU in which the fellow trained. The majority of respondents reported that patient care was positively affected by APPs with nearly two-thirds of PDs reporting that fellowship training was also positively impacted. Conclusions Our survey revealed that APPs are utilized in a large number of US AMCs with critical care training programs. Program director respondents believed that patient care and fellowship training were positively impacted by APPs.

Objective: To review the pathophysiology of anemia, as well as transfusion-related complications and indications for red blood cell (RBC) transfusion, in critically ill children. Although allogeneic blood has become increasingly safer from infectious agents, mounting evidence indicates that RBC transfusions are associated with complications and unfavorable outcomes. As a result, there has been growing interest and efforts to limit RBC transfusion, and indications are being revisited and revamped. Although a so-called restrictive RBC transfusion strategy has been shown to improve morbidity and mortality in critically ill adults, there have been relatively few studies on RBC transfusion performed in critically ill children. Data Sources: Published literature on transfusion medicine and outcomes of RBC transfusion. Study Selection, Data Extraction, and Synthesis: After a brief overview of physiology of oxygen transportation, anemia compensation, and current transfusion guidelines based on available literature, risks and outcomes of transfusion in general and in critically ill children are summarized in conjunction with studies investigating the safety of restrictive transfusion strategies in this patient population. Conclusions: The available evidence does not support the extensive use of RBC transfusions in general or critically ill patients. Transfusions are still associated with risks, and although their benefits are established in limited situations, the associated negative outcomes in many more patients must be closely addressed. Given the frequency of anemia and its proven negative outcomes, transfusion decisions in the critically ill children should be based on individual patient’s characteristics rather than generalized triggers, with consideration of potential risks and benefits, and available blood conservation strategies that can reduce transfusion needs. (Pediatr Crit Care Med 2011; 12:174 –183)

Background: Much is still unknown about the actual incidence of anesthesia-related cardiac arrest in the United States. Methods: The authors identified all of the cases of cardiac arrest from their quality improvement database from 1999 to 2009 and submitted them for review by an independent study commission to give them the best estimate of anesthesia-related cardiac arrest at their institution. One hundred sixty perioperative cardiac arrests within 24 h of surgery were identified from an anesthesia database of 217,365 anesthetics. An independent study commission reviewed all case abstracts to determine which cardiac arrests were anesthesia-attributable or anesthesia-contributory. Anesthesia-attributable cardiac arrests were those cases in which anesthesia was determined to be the primary cause of cardiac arrest. Anesthesia-contributory cardiac arrests were those cases where anesthesia was determined to have contributed to the cardiac arrest. Results: Fourteen cardiac arrests were anesthesia-attributable, resulting in an incidence of 0.6 per 10,000 anesthetics (95% CI, 0.4 to 1.1). Twenty-three cardiac arrests were found to be anesthesia-contributory resulting in an incidence of 1.1 per 10,000 anesthetics (95% CI, 0.7 to 1.6). Sixty-four percent of anesthesia-attributable cardiac arrests were caused by airway complications that occurred primarily with induction, emergence, or in the postanesthesia care unit, and mortality was 29%. Anesthesia-contributory cardiac arrest occurred during all phases of the anesthesia, and mortality was 70%. Conclusion: As judged by an independent study commission, anesthesia-related cardiac arrest occurred in 37 of 160 cardiac arrests within the 24-h perioperative period.