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As patients continue to live longer from diseases that predispose them to right ventricular (RV) dysfunction or failure, many more patients will require surgery for acute or chronic health issues. Because RV dysfunction results in significant perioperative morbidity if not adequately assessed or managed, understanding appropriate assessment and treatments is important in preventing subsequent morbidity and mortality in the perioperative period. In light of the epidemiology of right heart disease, a working knowledge of right heart anatomy and physiology and an understanding of the implications of right-sided heart function for perioperative care are essential for perioperative practitioners. However, a significant knowledge gap exists concerning this topic. This manuscript is one part of a collection of papers from the PeriOperative Quality Initiative (POQI) IX Conference focusing on "Current Perspectives on the Right Heart in the Perioperative Period." This review aims to provide perioperative clinicians with an essential understanding of right heart physiology by answering five key questions on this topic and providing an explanation of seven fundamental concepts concerning right heart physiology. [ABSTRACT FROM AUTHOR]

Author(s): Luis Fernando Gonzalez-Ciccarelli [sup.1], Raquel Bartz [sup.1], Dirk Varelmann [sup.1] Author Affiliations: (1) grid.38142.3c, 000000041936754X, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital. Harvard Medical School, [...]

Purpose Sepsis-associated immunosuppression increases hospital-acquired infection and viral reactivation risk. A key underlying mechanism is programmed cell death protein-1 (PD-1)-mediated T-cell function impairment. This is one of the first clinical safety and pharmacokinetics (PK) assessments of the anti-PD-1 antibody nivolumab and its effect on immune biomarkers in sepsis. Methods Randomized, double-blind, parallel-group, Phase 1b study in 31 adults at 10 US hospital ICUs with sepsis diagnosed [greater than or equal to] 24 h before study treatment, [greater than or equal to] 1 organ dysfunction, and absolute lymphocyte count [less than or equal to] 1.1 x 10.sup.3 cells/[mu]L. Participants received one nivolumab dose [480 mg (n = 15) or 960 mg (n = 16)]; follow-up was 90 days. Primary endpoints were safety and PK parameters. Results Twelve deaths occurred [n = 6 per study arm; 40% (480 mg) and 37.5% (960 mg)]. Serious AEs occurred in eight participants [n = 1, 6.7% (480 mg); n = 7, 43.8% (960 mg)]. AEs considered by the investigator to be possibly drug-related and immune-mediated occurred in five participants [n = 2, 13.3% (480 mg); n = 3, 18.8% (960 mg)]. Mean ± SD terminal half-life was 14.7 ± 5.3 (480 mg) and 15.8 ± 7.9 (960 mg) days. All participants maintained > 90% receptor occupancy (RO) 28 days post-infusion. Median (Q1, Q3) mHLA-DR levels increased to 11,531 (6528, 19,495) and 11,449 (6225, 16,698) mAbs/cell in the 480- and 960-mg arms by day 14, respectively. Pro-inflammatory cytokine levels did not increase. Conclusions In this sepsis population, nivolumab administration did not result in unexpected safety findings or indicate any 'cytokine storm'. The PK profile maintained RO > 90% for [greater than or equal to] 28 days. Further efficacy and safety studies are warranted. Trial registration number (clinicaltrials.gov) NCT02960854., Author(s): Richard S. Hotchkiss [sup.1], Elizabeth Colston [sup.2], Sachin Yende [sup.3] [sup.4], Elliott D. Crouser [sup.5], Greg S. Martin [sup.6], Timothy Albertson [sup.7] [sup.8], Raquel R. Bartz [sup.9], Scott C. [...]

Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting in inflammation and multiple organ involvement. A distinction should be made between connective tissue diseases (mainly systemic lupus erythematosus, systemic scleroderma, inflammatory muscle diseases, and rheumatoid arthritis) and vasculitides (mainly small-vessel vasculitis such as antineutrophil cytoplasmic antibody-associated vasculitis and immune-complex mediated vasculitis). Admission of patients with autoimmune diseases to the intensive care unit (ICU) is often triggered by disease flare-ups, infections, and organ failure and is associated with high mortality rates. Management of these patients is complex, including prompt disease identification, immunosuppressive treatment initiation, and life-sustaining therapies, and requires multi-disciplinary involvement. Data about autoimmune diseases in the ICU are limited and there is a need for multicenter, international collaboration to improve patients' diagnosis, management, and outcomes. The objective of this narrative review is to summarize the epidemiology, clinical features, and selected management of severe systemic autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background: Older adults suffering from traumatic brain injury (TBI) are subject to higher injury burden and mortality. Do Not Resuscitate (DNR) orders are used to provide care aligned with patient wishes, but they may not be equitably distributed across racial/ethnic groups. We examined racial/ethnic differences in the prevalence of DNR orders at hospital admission in older patients with severe TBI. Methods: We conducted a retrospective cohort study using the National Trauma Databank (NTDB) between 2007 to 2016. We examined patients ≥ 65 years with severe TBI. For our primary aim, the exposure was race/ethnicity and outcome was the presence of a documented DNR at hospital admission. We conducted an exploratory analysis of hospital outcomes including hospital mortality, discharge to hospice, and healthcare utilization (intracranial pressure monitor placement, hospital LOS, and duration of mechanical ventilation). Results: Compared to White patients, Black patients (OR 0.48, 95% CI 0.35-0.64), Hispanic patients (OR 0.54, 95% CI 0.400.70), and Asian patients (OR 0.63, 95% CI 0.44-0.90) had decreased odds of having a DNR order at hospital admission. Patients with DNRs had increased odds of hospital mortality (OR 2.16, 95% CI 1.94-2.42), discharge to hospice (OR 2.08, 95% CI 1.75-2.46), shorter hospital LOS (-2.07 days, 95% CI -3.07 to -1.08) and duration of mechanical ventilation (-1.09 days, 95% CI -1.52 to -0.67). There was no significant difference in the utilization of ICP monitoring (OR 0.94, 95% CI 0.78-1.12). Conclusions: We found significant racial and ethnic differences in the utilization of DNR orders among older patients with severe TBI. Additionally. DNR orders at hospital admission were associated with increased in-hospital mortality, increased hospice utilization, and decreased healthcare utilization. Future studies should examine mechanisms underlying race-based differences in DNR utilization. [ABSTRACT FROM AUTHOR]

Background: Heart failure affects >6 million people in the United States alone and is most prevalent in Black patients who suffer the highest mortality risk. Yet prior studies have suggested that Black patients are less likely to receive advanced heart failure therapy. We hypothesized that Black patients would have decreased rates of durable left ventricular assist device (LVAD) implantation within our expansive heart failure program.Methods: A retrospective single-center cohort study was conducted at a single high-volume academic medical center. Patients between 18 and 85 years admitted with a diagnosis of cardiogenic shock or congestive heart failure between 1, 2013 and 12, 2017 with a left ventricular ejection fraction < 30% and inotropic dependence or need for mechanical circulatory support were included. Patients with contraindications to durable LVAD were excluded. An adjusted logistic regression model for durable LVAD implantation within 90 days of the index admission was used to determine the effect of race on durable LVAD implantation.Results: Among the 702 study patients (60.9% White, 34.1% Black), durable LVAD implantation was performed within 90 days of the index admission in 183 (26%) of the cohort. After multivariate analysis, Black patients were not found to have a statistically significant difference in durable LVAD implantation rates compared to White patients in our study (OR: 0.68 [95% confidence interval: 0.45-1.04; p: .074]).Conclusions: Black patients in our study did not have a statistically significant difference in the rate of durable LVAD implantation compared with White patients after adjustments were made for age, sex, socioeconomic, and clinical covariates. Larger prospective studies are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Elevated perioperative heart rate potentially causes perioperative myocardial injury because of imbalance in oxygen supply and demand. However, large multicenter studies evaluating early postoperative heart rate and major adverse cardiac and cerebrovascular events (MACCEs) are lacking. Objective: To assess the associations of 4 postoperative heart rate assessment methods with in-hospital MACCEs after elective coronary artery bypass grafting (CABG). Methods: Using data from the eICU Collaborative Research Database in the United States from 2014 to 2015, the study evaluated postoperative heart rate measured during hospitalization within 24 hours after intensive care unit admission. Four heart rate assessment methods were evaluated: maximum heart rate, duration above heart rate 100/min, area above heart rate 100/min, and time-weighted average heart rate. The outcome was in-hospital MACCEs, defined as a composite of in-hospital death, myocardial infarction, angina, arrhythmia, heart failure, stroke, cardiac arrest, or repeat revascularization. Results: Among 2585 patients, the crude rate of in-hospital MACCEs was 6.2%. In multivariable logistic regression analysis, the adjusted odds ratios (95% CI) for in-hospital MAC-CEs assessed by maximum heart rate in each heart rate category (beats per minute: >100-110, >110-120, >120-130, and >130) were 1.43 (0.95-2.15), 0.98 (0.56-1.64), 1.47 (0.76-2.69), and 1.71 (0.80-3.35), respectively. Similarly, none of the other 3 methods were associated with MACCEs. Conclusions: More research is needed to assess the usefulness of heart rate measurement in patients after CABG. [ABSTRACT FROM AUTHOR]

Objective: To examine racial and ethnic differences in the utilization of 3 interventions (tracheostomy placement, gastrostomy tube placement, and hospice utilization) among patients with severe acute brain injury (SABI). Design: Retrospective cohort study. Setting: Data from the National Inpatient Sample, from 2002 to 2012. Patients: Adult patients with SABI defined as a primary diagnosis of stroke, traumatic brain injury, or post-cardiac arrest who received greater than 96 hours of mechanical ventilation. Exposure: Race/ethnicity, stratified into 5 categories (white, black, Hispanic, Asian, and other). Measurements and Main Results: Data from 86 246 patients were included in the cohort, with a mean (standard deviation) age of 60 (18) years. In multivariable analysis, compared to white patients, black patients had an 20% increased risk of tracheostomy utilization (relative risk [RR]: 1.20, 95% CI: 1.16-1.24, P < .001), Hispanic patients had a 10% increased risk (RR: 1.10, 95% CI: 1.06-1.14, P < .001), Asian patients had an 8% increased risk (RR: 1.08, 95% CI: 1.01-1.16, P = .02), and other race patients had an 10% increased risk (RR: 1.10, 95% CI: 1.04-1.16, P < .001). A similar relationship was observed for gastrostomy utilization. In multivariable analysis, compared to white patients, black patients had a 25% decreased risk of hospice discharge (RR: 0.75, 95% CI: 0.67-0.85, P < .001), Hispanic patients had a 20% decreased risk (RR: 0.80, 95% CI: 0.69-0.94, P < .01), and Asian patients had a 47% decreased risk (RR: 0.53, 95% CI: 0.39-0.73, P < .001). There was no observed relationship between race/ethnicity and in-hospital mortality. Conclusions: Minority race was associated with increased utilization of tracheostomy and gastrostomy, as well as decreased hospice utilization among patients with SABI. Further research is needed to better understand the mechanisms underlying these race-based differences in critical care. [ABSTRACT FROM AUTHOR]

Background: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown.Research Question: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States?Study Design and Methods: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao2 to Fio2 ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H2O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed.Results: A total of 2,466 patients were enrolled. Median baseline Pao2 to Fio2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H2O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR.Interpretation: Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes.Trial Registry: ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic created pressure to delay inpatient elective surgery to increase US health care capacity. This study examined the extent to which common inpatient elective operations consume acute care resources. Methods: This cross-sectional study used the Premier Healthcare Database to examine the distribution of inpatient elective operations in the United States from the fourth quarter of 2015 through the second quarter of 2018. Primary outcomes were measures of acute care use after 4 common elective operations: joint replacement, spinal fusion, bariatric surgery, and coronary artery bypass grafting. A framework for matching changing demand with changes in supply was created by overlaying acute care data with publicly available outbreak capacity data. Results: Elective coronary artery bypass grafting (n = 117 423) had the highest acute care use: 92.8% of patients used intensive care unit beds, 89.1% required postoperative mechanical ventilation, 41.0% required red blood cell transfusions, and 13.3% were readmitted within 90 days of surgery. Acute care use was also substantial after spinal fusion (n = 203 789): 8.3% of patients used intensive care unit beds, 2.2% required postoperative mechanical ventilation, 9.2% required red blood cell transfusions, and 9.3% were readmitted within 90 days of surgery. An example of a framework for matching hospital demand with elective surgery supply is provided. Conclusions: Acute care needs after elective surgery in the United States are consistent and predictable. When these data are overlaid with national hospital capacity models, rational decisions regarding matching supply to demand can be achieved to meet changing needs. [ABSTRACT FROM AUTHOR]

Background: The transition to the new ICD-10 (International Classification of Diseases, Tenth Revision) coding system in the U.S. poses challenges to the ability to consistently and accurately measure trends in comorbidities and complications. We examined the prevalence of comorbidities and postoperative medical complications before and after the transition from ICD-9 to ICD-10 among patients who underwent primary total hip or knee arthroplasty (THA or TKA). We hypothesized that the transition to ICD-10 codes was associated with discontinuity and slope change in comorbidities and medical complications.Methods: The Elixhauser comorbidities and medical complications were identified using the Premier Healthcare database from fiscal year (FY)2011 to FY2018. Using multivariable segmented regression models, we examined the changes in the levels and slopes after the transition from ICD-9 to ICD-10 coding. Odds ratios (ORs) of <1 and >1 indicate decreases and increases, respectively, in levels and slopes.Results: Overall, 2,006,581 patients who underwent primary THA or TKA were identified. The mean age was 65.9 ± 10.5 years, and the median length of the hospital stay was 2 days (interquartile range [IQR], 2 to 3 days). Of the comorbidities studied, congestive heart failure, hypertension, and obesity had a statistically significant but clinically small discontinuity after the transition from ICD-9 to ICD-10 coding. Of the complications, pneumonia (OR = 0.66, 95% confidence interval [CI] = 0.48 to 0.90), acute respiratory failure (OR = 1.88, 95% CI = 1.52 to 2.33), sepsis (OR = 2.54, 95% CI = 1.45 to 4.44), and urinary tract infection (OR = 1.79, 95% CI = 1.32 to 2.42) demonstrated statistically significant discontinuity. Alcohol abuse and paralysis had an increasing prevalence before the ICD transition, followed by a decreasing prevalence after the transition. In contrast, metastatic cancer, weight loss, and acquired immunodeficiency syndrome (AIDS) showed a decreasing prevalence before the ICD transition followed by an increasing prevalence after the transition. Generally, complications showed a decreasing prevalence over time.Conclusions: The discontinuities after the transition from ICD-9 to ICD-10 coding were relatively small for most comorbidities. Medical complications generally showed a decreasing trend over the quarters studied. These findings support caution when conducting joint replacement studies that rely on ICD coding and include the ICD coding transition period. [ABSTRACT FROM AUTHOR]

Objective Multimodal analgesia has gained popularity in total hip arthroplasty (THA) and total knee arthroplasty (TKA), but large multicenter studies evaluating specific analgesic combinations are lacking. Design A retrospective study using the Premier Healthcare Database (2009–2014). Subjects Adults who underwent elective primary THA or TKA. Methods We categorized day-of-surgery analgesic exposure using eight mutually exclusive categories: acetaminophen (Ac), nonsteroidal anti-inflammatory drugs (Ns), gabapentinoids (Ga; gabapentin or pregabalin), Ac+Ns, Ac+Ga, Ns+Ga, Ac+Ns+Ga, and none of the three drugs. Multilevel models measured associations of the analgesic categories with a composite of postoperative pulmonary complications (PPCs). Results Among 863,139 patients, 75.2% received at least one of the three drugs. In multilevel models, compared with none of the three drugs, Ga use was associated with increased odds of PPCs when used alone (adjusted odds ratio [aOR] = 1.35, 95% confidence interval [CI] = 1.27 to 1.44), combined with Ac (aOR = 1.16, 95% CI = 1.08 to 1.26), or combined with Ns (aOR = 1.28, 95% CI = 1.21 to 1.34). In contrast, the Ac+Ns pair was associated with decreased odds of PPCs (OR = 0.86, 95% CI = 0.83 to 0.90) and lower opioid consumption. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery. Conclusions Gabapentinoids, alone and in single combination with either acetaminophen or nonsteroidal anti-inflammatory drugs, were associated with higher PPCs, whereas the Ac+Ns pair was associated with fewer PPCs and an opioid-sparing effect. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery. [ABSTRACT FROM AUTHOR]

Summary: Acute kidney injury (AKI) and primary graft dysfunction (PGD) are serious complications after heart transplantation (HT). The relationship between AKI and PGD is poorly understood. We sought to examine the incidence of AKI and identify risk factors associated with AKI. We hypothesized that PGD is one of the risk factors independently associated with post‐HT AKI. We gathered data for all adult patients who underwent HT between 2009 and 2014. AKI was defined by the KDIGO criteria. PGD was categorized using ISHLT criteria. We assessed univariable and multivariable logistic regression to identify risk factors independently associated with post‐HT AKI. Out of 316 patients, postoperative AKI occurred in 273 (86%) patients: 188 (68%) stage I, 44 (16%) stage II, and 41 (15%) stage III. Stage II/III AKI was associated with increased risk of mortality at 1 year. There was significant association between severe PGD and stage II/III AKI (P = 0.001, OR 3.63, 95% CI: 1.69–7.94). Other clinical factors significantly associated with stage II/III AKI included longer donor brain death duration and lower recipient baseline creatinine. We found that stage II/III AKI is common and independently associated with severe PGD. Another potentially modifiable risk factor is donor brain death duration. [ABSTRACT FROM AUTHOR]

Background: Gabapentinoids are commonly prescribed in perioperative multimodal analgesia protocols. Despite widespread use, the optimal dose to reduce opioid consumption while minimizing risks is unknown. We assessed dose-dependent effects of gabapentinoids on opioid consumption and postoperative pulmonary complications following total hip or knee arthroplasty (THA or TKA). We hypothesized that use of a gabapentinoid on the day of THA or TKA is associated with an increased risk of postoperative pulmonary complications in a dose-response fashion compared with the risk for patients who did not receive the drug.Methods: Using the Premier Database, we identified adults who underwent elective primary THA or TKA from 2009 to 2014. The exposure was receipt of a gabapentinoid (gabapentin or pregabalin) on the day of surgery. Gabapentin dose was categorized into 5 groups: none, 1 to 350, 351 to 700, 701 to 1,050, and >1,050 mg per day. Pregabalin dose was categorized into 4 groups: none, 1 to 110, 111 to 250, and >250 mg per day. The primary outcome was a composite of postoperative pulmonary complications, defined as respiratory failure, pneumonia, reintubation, pulmonary edema, noninvasive ventilation, or invasive mechanical ventilation.Results: Of 858,306 patients who underwent THA or TKA, 11.0% received gabapentin and 10.2% received pregabalin. The mean age (and standard deviation) of the patients was 65.6 ± 10.7 years, 39.6% were male, 78.2% were Caucasian, and 55.2% were covered by Medicare. In multilevel regression analysis, receipt of gabapentinoid at any dose on the day of surgery was associated with increased odds of postoperative pulmonary complications. Compared with no exposure to the drug being used by the particular group, all dose ranges of gabapentin and pregabalin were associated with greater odds of postoperative pulmonary complications (odds ratio, 95% confidence interval = 1.51, 1.40 to 1.63, for >1,050 mg of gabapentin and 1.81, 1.57 to 2.09, for >250 mg of pregabalin). We found no clinically meaningful associations between exposure to either gabapentin or pregabalin and perioperative opioid consumption or the length of the hospital stay.Conclusions: Exposure to gabapentinoids at any dose on the day of THA or TKA was associated with increased odds of postoperative pulmonary complications in a dose-response fashion, with minimal effects on perioperative opioid consumption.Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Purpose: Clinically available near-infrared spectroscopy (NIRS) devices use two to five wavelengths of light to measure the relative amounts of oxyhemoglobin and deoxyhemoglobin in tissue to determine tissue hemoglobin oxygen saturation (StO2). In addition to StO2, broadband NIRS devices (using hundreds of wavelengths of light) may be able to measure the oxidation state of mitochondrial cytochrome aa3 (Cytox) which reflects the subcellular energetic state. We hypothesize that broadband NIRS devices can measure Cytox independent of changes in hemoglobin saturation.Methods: In this prospective non-randomized study, 20 male Sprague-Dawley rats (300 g) were anesthetized with isoflurane, tracheally intubated, and ventilated with 100% O2 containing 2% isoflurane. They were subsequently instrumented with a broadband NIRS device that used a halogen light source coupled to an emitting fibreoptic cable. Three receiving fibreoptic cables were utilized; one analyzed the light source and the other two were directed at the base of the skull. Each receiving fibre was connected to a spectrometer to measure light intensity. Sodium cyanide (NaCN) 5 mg·kg-1 iv was injected in order to produce cytochrome aa3 reduction. Two to three minutes after injection, oxygen was eliminated and 100% nitrogen (i.e., anoxia) was used for ventilation in order to induce a reduction in both cytochrome aa3 and hemoglobin desaturation. Changes in the cytochrome oxidation state and hemoglobin oxygenation were calculated using a broadband algorithm and compared before and after both the NaCN and anoxia interventions.Results: The NaCN injection resulted in a decrease in median [interquartile range (IQR)] deoxyhemoglobin (-0.014 [-0.29 to -0.005] arbitrary units [AU]; P < 0.001), an increase in oxyhemoglobin (0.013 [-0.011 to 0.031] AU; P < 0.001), and a reduction in cytochrome aa3 (-0.015 [-0.020 to -0.011] AU; P < 0.001). Anoxia resulted in an increase in median [IQR] deoxyhemoglobin (0.13 [0.11 to 0.18] AU; P < 0.001), a decrease in oxyhemoglobin (-0.17 [-0.22 to -0.15] AU; P < 0.001), and a reduction in cytochrome aa3 (-0.04 [-0.06 to -0.03] AU; P < 0.001).Conclusion: Broadband NIRS can effectively measure the directionality of changes in both Cytox and StO2 by uncoupling the cytochrome and hemoglobin signals through inhibition of the electron transport chain and anoxia. [ABSTRACT FROM AUTHOR]

Background The number of adults referred to high-volume centers for extracorporeal membrane oxygenation (ECMO) is increasing. Outcomes of patients requiring transport are not well characterized, and referral guidelines are lacking. This study describes the experience and outcomes of a single high-volume center. Methods A retrospective study was performed that included adults undergoing ECMO between June 2009 and December 2015. Patient characteristics and outcomes were acquired from the medical record. Logistic regression was used to identify predictors of survival to hospital discharge. The Kaplan-Meier method was used to depict rates of survival. Results Of 133 patients, 77 (57.9%) underwent venoarterial (VA) ECMO and 56 (42.1%) underwent venovenous (VV) ECMO. Median transport distance was 88.8 miles (range 0.2–1,434 miles). Median duration of support was 6 days (range, 1–32.5 days). Age older than 60 years, pulmonary hypertension, and body mass index (BMI) greater than 30 were associated with worse survival to discharge for VA ECMO; a history of hypertension and presence of left ventricular (LV) vent were associated with better survival. Age older than 60 years and diabetes were associated with worse survival to hospital discharge for VV ECMO. Survival to decannulation was 66.2% and 76.8%, and to hospital discharge it was 48.1% and 69.6% for VA and VV ECMO, respectively. Of hospital survivors, Kaplan-Meier estimates of 1-year survival were 82.4% and 95.5% for VA and VV, respectively. Conclusions Outcomes are favorable after transport to high-volume ECMO centers. Guidelines and infrastructure for short- and long-distance ECMO transport is imperative for the efficient and successful management of these patients. [ABSTRACT FROM AUTHOR]

Patients who are critically ill following surgical or traumatic injury often present with coagulopathy as a component of the complex multisystem dysfunction that clinicians must rapidly diagnose and treat in the intensive care environment. Failure to recognize coagulopathy while volume resuscitation with crystalloid or colloid takes place, or an unbalanced transfusion strategy focused on packed red blood cell transfusion can all significantly worsen coagulopathy, leading to increased transfusion requirements and poor outcomes. Even an optimized transfusion strategy directed at correcting coagulopathy and maintaining clotting factor levels carries the risk of a number of transfusion reactions including transfusion-related acute lung injury, transfusion-related circulatory overload, anaphylaxis, and septic shock. A number of adjunctive strategies can be used either to augment a balanced transfusion approach or as alternatives to blood component therapy. Coupled with an appropriate and timely laboratory testing, this approach can quickly diagnose a patient's specific coagulopathy and work to correct it as quickly as possible, minimizing the requirement of blood transfusion and the pathophysiologic effects of excessive bleeding and fibrinolysis. We will review the literature supporting this approach and provide insight into how these approaches can be best used to care for bleeding patients in the intensive care unit. Finally, the increasing use of several novel oral anticoagulants, novel antiplatelet drugs, and low–molecular weight heparin to clinical practice has complicated the care of the coagulopathic patient when these drugs are involved. Many clinicians familiar with heparin and warfarin reversal are not familiar with the optimal way to reverse the action of these new drugs. Patients treated with these drugs for a wide variety of conditions including atrial fibrillation, stroke, coronary artery stent, deep venous thrombosis, and pulmonary embolism will present for emergency surgery and will require management of pharmacologically induced postoperative coagulopathy. We will discuss optimized strategies for reversal of these agents and strategies that are currently under development. [ABSTRACT FROM AUTHOR]

Mitochondrial damage is often overlooked in acute lung injury (ALI), yet most of the lung's physiological processes, such as airway tone, mucociliary clearance, ventilation-perfusion (Va/Q) matching, and immune surveillance require aerobic energy provision. Because the cell's mitochondrial quality control (QC) process regulates the elimination and replacement of damaged mitochondria to maintain cell survival, we serially evaluated mitochondrial biogenesis and mitophagy in the alveolar regions of mice in a validated Staphylococcus aureus pneumonia model. We report that apart from cell lysis by direct contact with microbes, modest epithelial cell death was detected despite significant mitochondrial damage. Cell death by TdT-mediated dUTP nick-end labeling staining occurred on days 1 and 2 postinoculation: apoptosis shown by caspase-3 cleavage was present on days 1 and 2, while necroptosis shown by increased levels of phospho-mixed lineage kinase domain-like protein (MLKL) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1) was present on day 1. Cell death in alveolar type I (AT1) cells assessed by bronchoalveolar lavage fluid receptor for advanced glycation end points (RAGE) levels was high, yet AT2 cell death was limited while both mitochondrial biogenesis and mitophagy were induced. These mitochondrial QC mechanisms were evaluated mainly in AT2 cells by localizing increases in citrate synthase content, increases in nuclear mitochondrial biogenesis regulators nuclear respiratory factor-1 (NRF-1) and peroxisome proliferator-activated receptor-β coactivator-1β (PGC-1β), and increases in light chain 3B protein (LC3-I)/LC3II ratios. Concomitant changes in p62, Pink 1, and Parkin protein levels indicated activation of mitophagy. By confocal microscopy, mitochondrial biogenesis and mitophagy were often observed on day 1 within the same AT2 cells. These findings imply that mitochondrial QC activation in pneumoniadamaged AT2 cells promotes cell survival in support of alveolar function. [ABSTRACT FROM AUTHOR]