Development and Publication of Clinical Practice Parameters, Reviews, and Meta-analyses: A Report From the Society of Cardiovascular Anesthesiologists Presidential Task Force.

The Society of Cardiovascular Anesthesiologists (SCA) is committed to improving the quality, safety, and value that cardiothoracic anesthesiologists bring to patient care. To fulfill this mission, the SCA supports the creation of peer-reviewed manuscripts that establish standards, produce guidelines, critically analyze the literature, interpret preexisting guidelines, and allow experts to engage in consensus opinion. The aim of this report, commissioned by the SCA President, is to summarize the distinctions among these publications and describe a novel SCA-supported framework that provides guidance to SCA members for the creation of these publications. The ultimate goal is that through a standardized and transparent process, the SCA will facilitate up-to-date education and implementation of best practices by cardiovascular and thoracic anesthesiologists to improve patient safety, quality of care, and outcomes.

Medical Malpractice Claims Related to Performance of Transesophageal Echocardiography by Anesthesiologists.

More than 300,000 adults have cardiac surgery in the United States annually, and most undergo intraoperative transesophageal echocardiography (TEE). This patient population is often older with multiple comorbidities, increasing their risk for complications for even routine procedures. Major morbidity or mortality caused by TEE is rare, and it is unknown how often such complications lead to malpractice lawsuits. The authors identified 13 cases out of 2,564 in a closed claims database that involved TEE and reviewed their etiology. Esophageal injury accounted for most of the suits, and only 2 were related to diagnosis. Most expert reviews deemed the care provided by the anesthesiologist to be appropriate.

Alpha-Gal Syndrome and Cardiac Surgery.

Galactose-alpha-1,3-galactose (alpha-gal) is a carbohydrate expressed by all mammals except for humans and certain old-world primates. It can be found in a plethora of products derived from mammals, including milk, organs, skeletal muscle and gelatin, in addition to products prepared with mammalian cells or constituents. In the late 2000s, an association between tick bites and the development of immunoglobulin E antibodies to the alpha-gal carbohydrate was discovered. The term "alpha-gal syndrome" (AGS) was then coined to describe allergic reactions to mammalian meat or other alpha-gal-containing products derived from mammals. Symptoms are often delayed several hours from consumption and can be urticarial and/or gastrointestinal. Medications and bioprosthetic inserts derived from mammals were also noted to cause allergic reactions in affected patients. Cardiac surgery, in particular, is considered high risk, given that unfractionated heparin has a bovine or porcine origin and is administered in large doses for cardiopulmonary bypass. Bioprosthetic valves have similar origins and risks. Awareness of AGS in cardiac surgery patients can lead to decreased risk preoperatively and inform management perioperatively and postoperatively. In this narrative review, we have reviewed the published literature relevant to AGS in patients undergoing cardiac surgery and shared our treatment approach.

Association of Intraoperative Red Blood Cell Transfusions With Venous Thromboembolism and Adverse Outcomes After Cardiac Surgery.

OBJECTIVE: We determined whether intraoperative packed red blood cell (PRBC) transfusion was associated with a higher incidence of hospital-acquired venous thromboembolic (HA-VTE) complications and adverse outcomes after isolated coronary artery bypass grafting (CABG) surgery. BACKGROUND: Intraoperative PRBC has been associated with increased risk for postoperative deep venous thrombosis after cardiac surgery, but validation of these findings in a large, multi-institutional, national cohort of cardiac surgery patients has been lacking. METHODS: A registry-based cohort study of 751,893 patients with isolated CABG between January 1, 2015, to December 31, 2019. Using propensity score-weighted regression analysis, we analyzed the effect of intraoperative PRBC on the incidence of HA-VTE and adverse outcomes. RESULTS: Administration of 1, 2, 3, and ≥4 units of PRBC transfusion was associated with increased odds for HA-VTE [odds ratios (ORs): 1.27 (1.22-1.32), 1.21 (1.16-1.26), 1.93 (1.85-2.00), 1.82 (1.75-1.89)], deep venous thrombosis [ORs: 1.39 (1.33-1.46), 1.38 (1.32-1.44), 2.18 (2.09-2.28), 1.82 (1.74-1.91], operative mortality [ORs: 1.11 (1.08-1.14), 1.16 (1.13-1.19), 1.29 (1.26-1.32), 1.47 (1.43-1.50)], readmission within 30 days [ORs: 1.05 (1.04-1.06), 1.16 (1.13-1.19), 1.29 (1.26-1.32), 1.47 (1.43-1.50)], and a prolonged postoperative length of stay [mean difference in days, 0.23 (0.19-0.27), 0.34 (0.30-0.39), 0.69 (0.64-0.74), 0.77 (0.72-0.820]. The odds of pulmonary venous thromboembolism were lower for patients transfused with 1 or 2 units [ORs: 0.98 (0.91-1.06), 0.75 (0.68-0.81)] of PRBC but remained significantly elevated for those receiving 3 and ≥4 units [ORs: 1.19 (1.09-1.29), 1.35 (1.25-1.48)]. CONCLUSIONS: Intraoperative PRBC transfusion was associated with HA-VTE and adverse outcomes after isolated CABG surgery.

Trajectory of PaO2/FiO2 Ratio in Shock After Angiotensin II.

INTRODUCTION: High-dose catecholamines can impair hypoxic pulmonary vasoconstriction and increase shunt fraction. We aimed to determine if Angiotensin II (Ang-2) is associated with improved PaO2/FiO2 and SpO2/FiO2 in patients in shock. METHODS: Adult patients at four tertiary care centers and one community hospital in the United States who received Ang-2 from July 2018-September 2020 were included in this retrospective, observational cohort study. PaO2, SpO2, and FiO2 were measured at 13 timepoints during the 48-h before and after Ang-2 initiation. Piecewise linear mixed models of PaO2/FiO2 and SpO2/FiO2 were created to evaluate hourly changes in oxygenation after Ang-2 initiation. The difference in the proportion of patients with PaO2/FiO2 ≤ 300 mm Hg at the time of Ang-2 initiation and 48 h after was also examined. RESULTS: The study included 254 patients. In the 48 h prior to Ang-2 initiation, oxygenation was significantly declining (hourly PaO2/FiO2 change -4.7 mm Hg/hr, 95% CI - 6.0 to -3.5, p < .001; hourly SpO2/FiO2 change -3.1/hr, 95% CI-3.7 to -2.4, p < .001). Ang-2 treatment was associated with significant improvements in PaO2/FiO2 and SpO2/FiO2 in the 48-h after initiation (hourly PaO2/FiO2 change +1.5 mm Hg/hr, 95% CI 0.5-2.5, p = .003; hourly SpO2/FiO2 change +0.9/hr, 95% CI 0.5-1.2, p < .001). The difference in the hourly change in oxygenation before and after Ang-2 initiation was also significant (pinteraction < 0.001 for both PaO2/FiO2 and SpO2/FiO2). This improvement was associated with significantly fewer patients having a PaO2/FiO2 ≤ 300 mm Hg at 48 h compared to baseline (mean difference -14.9%, 95% CI -25.3% to -4.6%, p = .011). Subgroup analysis found that patients with either a baseline PaO2/FiO2 ≤ 300 mm Hg or a norepinephrine-equivalent dose requirement >0.2 µg/kg/min had the greatest associations with oxygenation improvement. CONCLUSIONS: Ang-2 is associated with improved PaO2/FiO2 and SpO2/FiO2. The mechanisms for this improvement are not entirely clear but may be due to catecholamine-sparing effect or may also be related to improved ventilation-perfusion matching, intrapulmonary shunt, or oxygen delivery.

Factor VIII: A Dynamic Modulator of Hemostasis and Thrombosis in Trauma.

A trace amount of thrombin cleaves factor VIII (FVIII) into an active form (FVIIIa), which catalyzes FIXa-mediated activation of FX on the activated platelet surface. FVIII rapidly binds to von Willebrand factor (VWF) after secretion and becomes highly concentrated via VWF-platelet interaction at a site of endothelial inflammation or injury. Circulating levels of FVIII and VWF are influenced by age, blood type (nontype O > type O), and metabolic syndromes. In the latter, hypercoagulability is associated with chronic inflammation (known as thrombo-inflammation). In acute stress including trauma, releasable pools of FVIII/VWF are secreted from the Weibel-Palade bodies in the endothelium and then augment local platelet accumulation, thrombin generation, and leukocyte recruitment. Early systemic increases of FVIII/VWF (>200% of normal) levels in trauma result in a lower sensitivity of contact-activated clotting time (activated partial thromboplastin time [aPTT] or viscoelastic coagulation test [VCT]). However, in severely injured patients, multiple serine proteases (FXa plasmin and activated protein C [APC]) are locally activated and may be systemically released. Severity of traumatic injury correlates with prolonged aPTT and elevated activation markers of FXa, plasmin, and APC, culminating in a poor prognosis. In a subset of acute trauma patients, cryoprecipitate that contains fibrinogen, FVIII/VWF, and FXIII is theoretically advantageous over purified fibrinogen concentrate to promote stable clot formation, but comparative efficacy data are lacking. In chronic inflammation or subacute phase of trauma, elevated FVIII/VWF contributes to the pathogenesis of venous thrombosis by enhancing not only thrombin generation but also augmenting inflammatory functions. Future developments in coagulation monitoring specific to trauma patients, and targeted to enhancement or inhibition of FVIII/VWF, are likely to help clinicians gain better control of hemostasis and thromboprophylaxis. The main goal of this narrative is to review the physiological functions and regulations of FVIII and implications of FVIII in coagulation monitoring and thromboembolic complications in major trauma patients.

Relationships Between Body Mass Index, Allogeneic Transfusion, and Surgical Site Infection After Knee and Hip Arthroplasty Surgery.

BACKGROUND: Increased body mass index (BMI) is considered as an important factor that affects the need for total knee and hip arthroplasty (TKA/THA) and the rate of perioperative complications. Previous investigations have not fully established the relationship of BMI and perioperative transfusion with surgical site infection (SSI) or the relationship of BMI and perioperative transfusion after TKA or THA. METHODS: The National Surgical Quality Improvement Program database was used to perform a retrospective cohort study involving 333,223 TKA and 41,157 THA cases between 2011 and 2018. Multivariable regression assessed the associations of BMI (5 standard categories) and transfusion with SSI. Odds ratio (OR) of SSI was calculated relative to a normal BMI (18.5-24.9 kg/m 2 ) after adjustment of potential confounding factors. RESULTS: Perioperative transfusion decreased significantly over time for both TKA and THA; however, SSI rates remained steady at just under 1% for TKA and 3% for THA. In TKA, a higher OR for SSI was associated only with a BMI of 40+ (OR, 1.86; 95% confidence interval [CI], 1.60-2.18) compared to a referent BMI. In THA, increased ORs of SSI were seen for all BMI levels above normal and were highest for a BMI 40+ (OR, 3.08; 95% CI, 2.47-3.83). In TKA, ORs of transfusion decreased with increasing BMI and were lowest for a BMI 40+ (OR, 0.51; 95% CI, 0.47-0.54). In THA, ORs of transfusion began to increase slightly in overweight patients, reaching an OR of 1.36 (95% CI, 1.21-1.54) for a BMI 40+. CONCLUSIONS: SSI incidence remained unchanged despite continuous reductions in blood transfusion in TKA and THA patients over 8 years. In TKA, ORs for SSI increased, but ORs for transfusion decreased with increasing BMI above normal. Conversely, in THA, ORs for SSI and transfusion both increased for a BMI 40+, but only OR for transfusion increased in underweight patients. These findings suggest the importance of controlling obesity in reducing SSI following TKA and THA.

In Vitro Analysis of Platelet Adhesion, Aggregation, and Surface GP1bα Expression in Stored Refrigerated Whole Blood: A Pilot Study.

BACKGROUND: Warm, fresh whole blood (WB) has been used by the US military to treat casualties in Iraq and Afghanistan. Based on data in that setting, cold-stored WB has been used to treat hemorrhagic shock and severe bleeding in civilian trauma patients in the United States. In an exploratory study, we performed serial measurements of WB's composition and platelet function during cold storage. Our hypothesis was that in vitro platelet adhesion and aggregation would decrease over time. METHODS: WB samples were analyzed on storage days 5, 12, and 19. Hemoglobin, platelet count, blood gas parameters (pH, Po2, Pco2, and Spo2), and lactate were measured at each timepoint. Platelet adhesion and aggregation under high shear were assessed with a platelet function analyzer. Platelet aggregation under low shear was assessed using a lumi-aggregometer. Platelet activation was assessed by measuring dense granule release in response to high-dose thrombin. Platelet GP1bα levels were measured with flow cytometry, as a surrogate for adhesive capacity. Results at the 3 study timepoints were compared using repeat measures analysis of variance and post hoc Tukey tests. RESULTS: Measurable platelet count decreased from a mean of (163 + 53) × 109 platelets per liter at timepoint 1 to (107 + 32) × 109 at timepoint 3 (P = .02). Mean closure time on the platelet function analyzer (PFA)-100 adenosine diphosphate (ADP)/collagen test increased from 208.7 + 91.5 seconds at timepoint 1 to 390.0 + 148.3 at timepoint 3 (P = .04). Mean peak granule release in response to thrombin decreased significantly from 0.7 + 0.3 nmol at timepoint 1 to 0.4 + 0.3 at timepoint 3 (P = .05). Mean GP1bα surface expression decreased from 232,552.8 + 32,887.0 relative fluorescence units at timepoint 1 to 95,133.3 + 20,759.2 at timepoint 3 (P < .001). CONCLUSIONS: Our study demonstrated significant decreases in measurable platelet count, platelet adhesion, and aggregation under high shear, platelet activation, and surface GP1bα expression between cold-storage days 5 and 19. Further studies are needed to understand the significance of our findings and to what degree in vivo platelet function recovers after WB transfusion.

Heterogeneity in Clinical Practices for Post-Cardiotomy Extracorporeal Life Support: a Pilot Survey from the PELS-1 Multicenter Study.

BACKGROUND: High-quality evidence for post-cardiotomy extracorporeal life support (PC-ECLS) management is lacking. This study investigated the real-world PC-ECLS clinical practices. METHODS: This cross-sectional, multi-institutional, international pilot survey explored center organization, anticoagulation management, left ventricular unloading, distal limb perfusion, PC-ECLS monitoring and transfusions practices. Twenty-nine questions were distributed among 34 hospitals participating in the Post-cardiotomy Extra-Corporeal Life Support Study. RESULTS: Of the 32 centers [16 low-volume (50%); 16 high-volume (50%)] that responded, 16 (50%) had dedicated ECLS specialists. Twenty-six centers (81.3%) reported using additional mechanical circulatory supports. Anticoagulation practices were highly heterogeneous: 24 hospitals (75%) reported using patient's bleeding status as a guide, without a specific threshold in 54.2% of cases. Transfusion targets ranged 7-10 g/dL. Most centers used cardiac venting on a case-by-case basis (78.1%) and regular distal limb perfusion (84.4%). Nineteen (54.9%) centers reported dedicated monitoring protocols including daily echocardiography (87.5%), Swan-Ganz catheterization (40.6%), cerebral near-infrared spectroscopy (53.1%) and multimodal assessment of limb ischemia. Inspection of the circuit (71.9%), oxygenator pressure drop (68.8%), plasma free hemoglobin (75%), d-dimer (59.4%), lactate dehydrogenase (56.3%) and fibrinogen (46.9%) are used to diagnose hemolysis and thrombosis. CONCLUSIONS: This study shows remarkable heterogeneity in clinical practices for PC-ECLS management. More standardized protocols and better implementation of available evidence are recommended.

Impact of Preoperative Hematocrit, Body Mass Index, and Red Cell Mass on Allogeneic Blood Product Usage in Adult Cardiac Surgical Patients: Report From a Statewide Quality Initiative.

OBJECTIVE: The study aims were to evaluate current blood transfusion practice in cardiac surgical patients and to explore associations between preoperative anemia, body mass index (BMI), red blood cell (RBC) mass, and allogeneic transfusion. DESIGN: Multicenter retrospective study. SETTING: Academic and non-academic centers. PARTICIPANTS AND INTERVENTIONS: After Institutional Review Board approval, 26,499 patients who underwent coronary artery bypass grafting ± valve replacement/repair between 2011 and 2019 were included from the Maryland Cardiac Surgery Quality Initiative database. Patients were stratified into BMI categories (<25, 25 to <30, and ≥30 kg/m2), and a multivariable logistic regression model was fit to determine if preoperative hematocrit, BMI, and RBC mass were associated independently with allogeneic transfusion. RESULTS: Preoperative anemia was found in 55.4%, and any transfusion was administered to 49.3% of the entire cohort. Females and older patients had lower BMI and RBC mass. Increased RBC and cryoprecipitate transfusions occurred more frequently after surgery in the lower BMI group. After adjustments, increased transfusion was associated with a BMI <25 relative to a BMI ≥30 at an odds ratio (OR) of 1.26 (95% confidence interval [CI]: 1.08-1.39). For each 1% increase in preoperative hematocrit, transfusion was decreased by 9% (OR: 0.91; 95% CI: 0.90-0.92). For every 500 mL increase in RBC mass, there was a 43% reduction of transfusion (OR: 0.57; 95% CI: 0.55-0.58). CONCLUSIONS: Transfusion probability modeling based on calculated RBC mass eliminated sex differences in transfusion risk based on preoperative hematocrit, and may better delineate which patients may benefit from more rigorous perioperative blood conservation strategy.

Spinal Cord Infarction With Prolonged Femoral Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: There have been sporadic reports of ischemic spinal cord injury (SCI) during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. The authors observed a troubling pattern of this catastrophic complication and evaluated the potential mechanisms of SCI related to ECMO. DESIGN: This study was a case series. SETTING: This study was performed at a single institution in a University setting. PARTICIPANTS: Patients requiring prolonged VA-ECMO were included. INTERVENTIONS: No interventions were done. This was an observational study. MEASUREMENTS AND MAIN RESULTS: Four hypotheses of etiology were considered: (1) hypercoagulable state/thromboembolism, (2) regional hypoxia/hypocarbia, (3) hyperperfusion and spinal cord edema, and (4) mechanical coverage of spinal arteries. The SCI involved the lower thoracic (T7-T12 level) spinal cord to the cauda equina in all patients. Seven out of 132 (5.3%) patients with prolonged VA-ECMO support developed SCI. The median time from ECMO cannulation to SCI was 7 (range: 6-17) days.There was no evidence of embolic SCI or extended regional hypoxia or hypocarbia. A unilateral, internal iliac artery was covered by the arterial cannula in 6/7 86%) patients, but flow into the internal iliac was demonstrated on imaging in all available patients. The median total flow (ECMO + intrinsic cardiac output) was 8.5 L/min (LPM), and indexed flow was 4.1 LPM/m2. The median central venous oxygen saturation was 88%, and intracranial pressure was measured at 30 mmHg in one patient, suggestive of hyperperfusion and spinal cord edema. CONCLUSIONS: An SCI is a serious complication of extended peripheral VA-ECMO support. Its etiology remains uncertain, but the authors' preliminary data suggested that spinal cord edema from hyperperfusion or venous congestion could contribute.

Factors Associated With a Discharge Against Medical Advice From an Emergency Department in Adult Patients With Appendicitis.

BACKGROUND: Delays in care can lead to worsened outcomes with acute appendicitis. To get timely treatment, patients must consent. OBJECTIVE: To determine if there are racial and socioeconomic differences in discharge against medical advice (DAMA) rates from an emergency department after the diagnosis of acute appendicitis. METHODS: Patients were identified retrospectively from the 2019 National Emergency Department Sample. The inclusion criteria were patients 18 years of age or older with acute appendicitis. Rates were compared using chi-square or Fisher's exact test. Odds ratios were determined using multiple logistic regression. A p value of 0.05 was used to determine statistical significance. RESULTS: The overall rate of DAMA was low (0.37%). Black patients had the highest rate, and White patients had the lowest (0.72% and 0.28%, respectively, p < 0.001). When controlling for covariates, Black patients also had a higher odds ratio (OR) for DAMA (OR 1.96, 95% confidence interval [CI] 1.29-2.97). Male patients had a higher unadjusted rate (0.47% vs. 0.26% in females, p < 0.001) and were at increased risk (OR 1.78, 95% CI 1.32-2.41). Patients between 30 and 65 years old had an increased risk (OR 1.48, 95% CI 1.10-2.0). Patients with government insurance or no insurance had higher rates than private insurance (0.57% and 0.56% vs. 0.23% respectively, p < 0.001). CONCLUSION: Race, insurance status, age, and male sex were all associated with increase in DAMA. Risk stratifying patients can help to determine how to best employ mitigations strategies. Reducing DAMA may be the next area for improving reducing disparities in appendicitis care.

Ultrafiltration in cardiac surgery: Results of a systematic review and meta-analysis.

Background: Ultrafiltration is used with cardiopulmonary bypass to reduce the effects of hemodilution and restore electrolyte balance. We performed a systematic review and meta-analysis to analyze the effect of conventional and modified ultrafiltration on intraoperative blood transfusion.Methods: Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, we systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library to perform a meta-analysis of studies of randomized controlled trials (RCTs) and observational studies evaluating conventional ultrafiltration (CUF) and modified ultrafiltration (MUF) on the primary outcome of intraoperative red cell transfusions.Results: A total of 7 RCTs (n = 928) were included, comparing modified ultrafiltration (n = 473 patients) to controls (n = 455 patients) and 2 observational studies (n = 47,007), comparing conventional ultrafiltration (n = 21,748) to controls (n = 25,427). Overall, MUF was associated with transfusion of fewer intraoperative red cell units per patient (n = 7); MD -0.73 units; 95% CI -1.12 to -0.35 p = 0.04; p for heterogeneity = 0.0001, I2 = 55%) compared to controls. CUF was no difference in intraoperative red cell transfusions compared to controls (n = 2); OR 3.09; 95% CI 0.26-36.59; p = 0.37; p for heterogeneity = 0.94, I2 = 0%. Review of the included observational studies revealed an association between larger volumes (>2.2 L in a 70 kg patient) of CUF and risk of acute kidney injury (AKI).Conclusion: The results of this systematic review and meta-analysis suggest that MUF is associated with fewer intraoperative red cell transfusions. Based on limited studies, CUF does not appear to be associated with a difference in intraoperative red cell transfusion.

A descriptive evaluation of causes of death in venovenous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become an important support modality for patients with acute respiratory failure refractory to optimal medical therapy, such as low tidal volume mechanical ventilator support, early paralytic infusion, and early prone positioning. The objective of this cohort study was to investigate the causes and timing of in-hospital mortality in patients on VV ECMO. All patients, excluding trauma and bridge to lung transplant, admitted 8/2014-6/2019 to a specialty ICU for VV ECMO were reviewed. Two hundred twenty-five patients were included. In-hospital mortality was 24.4% (n = 55). Most non-survivors (46/55, 84%) died prior to lung recovery and decannulation from VV ECMO. Most common cause of death (COD) for patients who died on VV ECMO was removal of life sustaining therapy (LST) in setting of multisystem organ failure (MSOF) (n = 24). Nine patients died a median of 9 days [6, 11] after decannulation. Most common COD in these patients was palliative withdrawal of LST due to poor prognosis (n = 3). Non-survivors were older and had worse predictive mortality scores than survivors. We found that death in patients supported with VV ECMO in our study most often occurs prior to decannulation and lung recovery. This study demonstrated that the most common cause of death in patients supported with VV ECMO was removal of LST due MSOF. Acute hemorrhage (systemic or intracranial) was not found to be a common cause of death in our patient population.

COVID-19 outcomes of venovenous extracorporeal membrane oxygenation for acute respiratory failure vs historical cohort of non-COVID-19 viral infections.

INTRODUCTION: Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become a support modality for patients with acute respiratory failure refractory to standard therapies. VV ECMO has been increasingly used during the current COVID-19 pandemic for patients with refractory respiratory failure. The object of this study was to evaluate the outcomes of VV ECMO in patients with COVID-19 compared to patients with non-COVID-19 viral infections. METHODS: We retrospectively reviewed all patients supported with VV ECMO between 8/2014 and 8/2020 whose etiology of illness was a viral pulmonary infection. The primary outcome of this study was to evaluate in-hospital mortality. The secondary outcomes included length of ECMO course, ventilator duration, hospital length of stay, incidence of adverse events through ECMO course. RESULTS: Eighty-nine patients were included (35 COVID-19 vs 54 non-COVID-19). Forty (74%) of the non-COVID-19 patients had influenza virus. Prior to cannulation, COVID-19 patients had longer ventilator duration (3 vs 1 day, p = .003), higher PaCO2 (64 vs 53 mmHg, p = .012), and white blood cell count (14 vs 9 ×103/µL, p = .004). Overall in-hospital mortality was 33.7% (n = 30). COVID-19 patients had a higher mortality (49% vs. 24%, p = .017) when compared to non-COVID-19 patients. COVID-19 survivors had longer median time on ECMO than non-COVID-19 survivors (24.4 vs 16.5 days p = .03) but had a similar hospital length of stay (HLOS) (41 vs 48 Extracorporeal Membrane Oxygenationdays p = .33). CONCLUSION: COVID-19 patients supported with VV ECMO have a higher mortality than non-COVID-19 patients. While COVID-19 survivors had significantly longer VV ECMO runs than non-COVID-19 survivors, HLOS was similar. This data add to a growing body of literature supporting the use of ECMO for potentially reversible causes of respiratory failure.

Sugammadex and blood loss during cervical spine fusion surgery.

Background and Aims: Sugammadex (SUG) has been associated with changes in coagulation studies. Most reports have concluded a lack of clinical significance based on surgical blood loss with SUG use at the end of surgery. Previous reports have not measured its use intraoperatively during ongoing blood loss. Our hypothesis was that the use of SUG intraoperatively may increase bleeding. Material and Methods: This was a single site retrospective study. Inclusion criteria were patients undergoing a primary posterior cervical spine fusion, aged over 18 years, between July 2015 and June 2021. The primary outcomes compared were intraoperative estimated blood loss (EBL) and postoperative drain output (PDO) between patients receiving SUG, neostigmine (NEO) and no NMB reversal agent. The objective was to determine if there was a difference in primary endpoints between patients administered SUG, NEO or no paralytic reversal agent. Primary endpoints were compared using analysis of variance with a P value of 0.05 used to determine statistical significance. Groups were compared using the Chi-squared test, rank sum or student's t test. A logistic regression model was constructed to account for differences between the groups. Results: There was no difference in median EBL or PDO between groups. The use of SUG was not associated with an increase in odds for >500 milliliters (ml) of EBL. Increasing duration of surgery and chronic kidney disease were both associated with an increased risk for EBL >500 ml. Conclusion: Intraoperative use of SUG was not associated with increased bleeding. Any coagulation laboratory abnormalities previously noted did not appear to have an associated clinical significance.

Renin Kinetics Are Superior to Lactate Kinetics for Predicting In-Hospital Mortality in Hypotensive Critically Ill Patients.

OBJECTIVES: Whole blood lactate concentration is widely used in shock states to assess perfusion. We aimed to determine if the change in plasma renin concentration over time would be superior to the change in lactate concentration for predicting in-hospital mortality in hypotensive patients on vasopressors. DESIGN: Prospective, observational cohort study. SETTING: Tertiary academic ICU. PATIENTS: Adult patients on vasopressors for greater than 6 hours to maintain a mean arterial pressure greater than or equal to 65 mm Hg during January 2020. INTERVENTIONS: Plasma renin concentrations were measured at enrollment and at 24, 48, and 72 hours. Whole blood lactate measurements were performed according to normal standard of care. Logistic regression was performed to evaluate whether the change in renin or lactate concentration could predict in-hospital mortality. Generalized estimating equations were used to analyze the association between renin and lactate concentration and in-hospital mortality. The area under the receiver operating characteristics curve was performed to measure the discriminative ability of initial and peak renin and lactate concentration to predict mortality. The association between renin and lactate concentration above the upper limit of normal at each timepoint with in-hospital mortality was also examined. MEASUREMENTS AND MAIN RESULTS: The study included 197 renin and 148 lactate samples obtained from 53 patients. The slope of the natural log (ln) of renin concentration was independently associated with mortality (adjusted odds ratio, 10.35; 95% CI, 1.40-76.34; p = 0.022), but the slope of ln-lactate concentration was not (adjusted odds ratio, 4.78; 95% CI, 0.03-772.64; p = 0.55). The generalized estimating equation models found that both ln-renin (adjusted odds ratio, 1.18; 95% CI, 1.02-1.37; p = 0.025) and ln-lactate (adjusted odds ratio, 2.38; 95% CI, 1.05-5.37; p = 0.037) were associated with mortality. Area under the receiver operating characteristics curve analysis demonstrated that initial renin could predict in-hospital mortality with fair discrimination (area under the receiver operating characteristics curve, 0.682; 95% CI, 0.503-0.836; p = 0.05), but initial lactate could not (area under the receiver operating characteristics curve, 0.615; 95% CI, 0.413-0.803; p = 0.27). Peak renin (area under the receiver operating characteristics curve, 0.728; 95% CI, 0.547-0.888; p = 0.01) and peak lactate (area under the receiver operating characteristics curve, 0.746; 95% CI, 0.584-0.876; p = 0.01) demonstrated moderate discrimination. There was no significant difference in discriminative ability between initial or peak renin and lactate concentration. At each study time point, a higher proportion of renin values exceeded the threshold of normal (40 pg/mL) in nonsurvivors than in survivors, but this association was not significant for lactate. CONCLUSIONS: Although there was no significant difference in the performance of renin and lactate when examining the absolute values of each laboratory, a positive rate of change in renin concentration, but not lactate concentration, over 72 hours was associated with in-hospital mortality. For each one-unit increase in the slope of ln-renin, the odds of mortality increased 10-fold. Renin levels greater than 40 pg/mL, but not lactate levels greater than 2 mmol/L, were associated with in-hospital mortality. These findings suggest that plasma renin kinetics may be superior to lactate kinetics in predicting mortality of hypotensive, critically ill patients.

The FIBTEM paradox: Do coronary artery bypass grafting patients with high baseline FIBTEM clot firmness need more allogeneic blood transfusion?

BACKGROUND: Fibrinogen thromboelastometry (FIBTEM) test is clinically used for rotational thromboelastometry as a surrogate measure of fibrinogen. Elevated fibrinogen might confer protection against bleeding after major surgery. This single-center study was conducted to assess any relationship between baseline FIBTEM value and exposure to allogeneic transfusion in patients undergoing coronary artery bypass grafting (CABG). STUDY DESIGN AND METHODS: Data were obtained retrospectively from local FIBTEM data and the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database between 2016 and 2019. Preoperative FIBTEM 10-min amplitude (A10) was categorized as low (≤ 18 mm), intermediate (19-23 mm), or high (≥24 mm). The primary outcome was any transfusion during the hospitalization, including red blood cells (RBCs), platelets, plasma, and cryoprecipitate. A multivariable regression model was used to adjust for confounders and calculate an odds ratio (OR) for any transfusion. RESULTS: The high FIBTEM group included more female and African-American patients, as well as urgent surgery. The STS predicted risks of morbidity and mortality were greater, and anemia was most prevalent with high FIBTEM. Unadjusted blood transfusion rates were increased with high FIBTEM due to RBC transfusion, but non-RBC transfusion was highest with low FIBTEM. After adjustments, a lower OR for transfusion was associated with high FIBTEM (0.426; 95% confidence interval, 0.199-0.914) compared to low FIBTEM. CONCLUSION: The high FIBTEM group frequently presented with anemia and comorbidities, and received more RBCs but not non-RBC products. Postoperative blood loss was less with high FIBTEM, and after adjustments, it conferred protection against any transfusion.

In vitro effects of emicizumab on activated clotting time in blood samples from cardiac surgical patients.

BACKGROUND: Heparin management in hemophilia A (HA) patients with a factor VIII (FVIII) inhibitor can be challenging due to severe activated clotting time (ACT) prolongations. It is important to better understand the impact of emicizumab, a FVIII mimetic on ACT, and tissue factor (TF)-based coagulation assays. METHODS: Whole blood from 18 patients undergoing cardiopulmonary bypass (CPB) were mixed in vitro with pooled normal plasma, FVIII-deficient or FVIII-inhibitor plasma to affect functional FVIII levels. ACTs and heparin concentration by protamine titration were measured in whole blood mixture with/without emicizumab (50-100 µg/ml). Thrombin generation and plasmin generation were measured in the patient's plasma mixed with normal plasma or FVIII-inhibitor plasma to assess the impact of emicizumab under low TF activation. RESULTS: FVIII inhibitors prolonged ACTs by 2.2-fold compared to those in normal plasma mixture at baseline. During CPB, ACTs in normal plasma mixture, and FVIII-deficient mixture were in 400s, but ACTs reached 900s in FVIII-inhibitor mixture. Emicizumab shortened ACTs by up to 100s in normal plasma mixture, and FVIII-deficient mixtures. ACTs remained over 600s in FVIII-inhibitor mixture, despite adding emicizumab at 100 µg/ml. Heparin concentration measured by TF-based protamine titration was unaffected. Emicizumab enhanced thrombin peak in the presence of FVIII inhibitors, whereas plasmin generation was mainly affected by thrombin generation, and systemic use of ɛ-aminocaproic acid. CONCLUSIONS: FVIII inhibitors extensively prolong ACTs in heparinized whole blood, and clinical levels of emicizumab partially reverse ACT values. Protamine titration should be considered for optimal heparin monitoring in emicizumab-treated patients with FVIII inhibitors.

A Multicenter Observational Cohort Study of Angiotensin II in Shock.

INTRODUCTION: Angiotensin II (Ang-2) is a non-catecholamine vasopressor that targets the renin-angiotensin-aldosterone system by agonism of the angiotensin type 1 receptor. Its utility as a vasopressor and a catecholamine-sparing agent was demonstrated in the pivotal ATHOS-3 trial, and numerous post-hoc analyses have shown reduced mortality in certain subsets of the population. METHODS: Consecutive adult patients at 5 centers who received Ang-2 from 2017-2020 were included in this multicenter, retrospective observational cohort study. Patient demographics, hemodynamics, and adverse events were collected. The primary outcomes of the study were the mean difference in MAP and norepinephrine (NEpi)-equivalent dose at hours 0 and 3 following initiation of Ang-2 therapy. RESULTS: One hundred and sixty-two patients were included in this study. The primary outcomes of an increase in MAP (mean difference 9.3 mmHg, 95% CI 6.4-12.1, p < 0.001) and a reduction in NEpi equivalent dose (mean difference 0.16 µg/kg/min, 95% CI 0.10-0.22, p < 0.001) between hours 0 and 3 were statistically significant. The median time to reach a MAP ≥65 was 16 minutes (IQR 5-60 min). After stratifying patients by the NED dose and number of vasopressors administered prior to the initiation of Ang-2, those with a NED dose < 0.2 µg/kg/min, NED dose < 0.3 µg/kg/min, or those on ≤ 3 vasopressors had a significantly greater reduction in NED by hour 3 than those patients above these thresholds. CONCLUSION: Ang-2 is an effective vasopressor and reduces catecholamine dose significantly. Its effect is rapid, with target MAP obtained within 30 minutes in most patients. Given the critical importance of adequate blood pressure to organ perfusion, Ang-2 should be considered when target MAP cannot be achieved with conventional vasopressors. Ang-2 should be utilized early in the course of shock, before the NED dose exceeds 0.2-0.3 µg/kg/min and before the initiation of the fourth-line vasopressor.