Life-threatening hemorrhage as defined by the critical administration threshold in nontraumatic critical bleeding: A descriptive observational study.

BACKGROUND: Evaluations of critical bleeding and massive transfusion have focused on traumatic hemorrhage. However, most critical bleeding in hospitalized patients occurs outside trauma. The purpose of this study was to provide an in-depth description examining the critical administration threshold (CAT; ≥3 units red blood cells (RBCs) in a 1-h period) occurrences in nontraumatic hemorrhage. This will assist in establishing the framework for future investigations in nontraumatic hemorrhage. METHODS: This is an observational cohort study of adults experiencing critical bleeding defined as being CAT+ during hospitalization from 2016 to 2021 at a single academic institution. A CAT episode started with administration of the first qualifying RBC unit and ended at the time of completion of the last allogeneic unit prior to a ≥4-h gap without subsequent transfusion. The primary goal was to describe demographic, clinical and transfusion characteristics of participants with nontraumatic critical bleeding. RESULTS: 2433 patients suffered critical bleeding, most often occurring in the operating room (71.1%) followed by the intensive care unit (20.8%). 57% occurred on the initial day of hospitalization, with a median duration of 138 (36, 303) minutes. The median number of RBCs transfused during the episode was 5 (4, 8), with median total allogeneic units of 9 (4, 9). Hospital mortality was 19.2%. The most common cause of death was multi-organ failure (50.3%), however death within 24 h was due to exsanguination (72.7%). DISCUSSION: The critical administration threshold may be employed to identify critical bleeding in non-trauma settings of life-threatening hemorrhage, with a mortality rate of approximately 20%.

Plasma, platelet and red blood cell transfusion ratios for life-threatening non-traumatic haemorrhage in medical and post-surgical patients: An observational study.

BACKGROUND AND OBJECTIVES: Despite the broad utilization of component-based transfusion strategies that aim to reconstitute whole blood during acute traumatic haemorrhage, data for haemorrhage occurring outside of trauma and surgery are limited. METHODS: This is an observational cohort study of adults experiencing critical non-traumatic, non-intraoperative haemorrhage during hospitalization at an academic medical centre from 2011 to 2015. The primary goal was to evaluate differences in plasma and platelet to red blood cell (RBC) transfusion ratios across patient demographic, clinical and laboratory characteristics. Secondarily, associations between transfusion ratios and clinical outcomes were assessed. RESULTS: Seven hundred nine patients were included: 498 (70.2%) medical and 211 (29.8%) post surgical. The gastrointestinal tract (36.7%) was the most common site of bleeding. Most patients received RBCs without plasma (35.5%) or platelets (54.2%). Among those receiving plasma, 82.3% received a plasma to RBC ratio < 1:1 at 24 h. For platelets, the most common ratio was 1-2:1 (52.9%). Transfusion ratios were generally consistent across comorbid disease severity, admission type and anatomic sites of bleeding. Higher plasma utilization was observed in the emergency department, while greater platelet utilization occurred in intensive care units. Higher transfusion ratios were observed in those with greater laboratory haemostatic abnormalities prior to the haemorrhagic event. Clinical outcome differences were limited, though greater platelet utilization in the first 24 h was associated with higher mortality and fewer hospital-free days. CONCLUSIONS: Transfusion ratios for critical non-traumatic haemorrhage were primarily related to laboratory abnormalities preceding the haemorrhagic event and practice environments. Clinical outcome differences across ratios were limited.

A Contemporary Analysis of Phlebotomy and Iatrogenic Anemia Development Throughout Hospitalization in Critically Ill Adults.

BACKGROUND: Anemia is common in critically ill patients and may be exacerbated through phlebotomy-associated iatrogenic blood loss. Differences in phlebotomy practice across patient demographic characteristics, clinical features, and practice environments are unclear. This investigation provides a comprehensive description of contemporary phlebotomy practices for critically ill adults. METHODS: This is an observational cohort study of adults ≥18 years of age requiring intensive care unit (ICU) admission between January 1, 2019, and December 31, 2019, at a large academic medical center. Descriptive statistics were utilized to summarize all phlebotomy episodes throughout hospitalization, with each phlebotomy episode defined by unique peripheral venous, central venous, or arterial accesses for laboratory draws, exclusive of finger sticks. Secondarily, financial costs of phlebotomy and the relationships between phlebotomy practices, hemoglobin concentrations, and red blood cell (RBC) transfusions were evaluated. RESULTS: A total of 6194 patients were included: 59% were men with a median (interquartile range) age of 66 (54-76) years and median ICU and hospital durations of 2.1 (1.4-3.9) and 7.1 (4.3-11.8) days, respectively. The median number of unique laboratory draws was 41 (18-88) throughout hospitalization, with a median volume of 232 (121-442) mL, corresponding to 5.2 (2.6-8.8) draws and 29 (19-43) mL per day. Waste (ie, discard) volume was responsible for 10.8% of total phlebotomy volume. Surgical patients had a higher number of phlebotomy episodes and greater total phlebotomy volumes compared to nonsurgical patients. Phlebotomy practices differed across ICU types, with the greatest frequency of laboratory draws in the cardiac surgical ICU and the greatest daily phlebotomy volume in the medical ICU. Across hospitalization, ICU environments had the greatest frequency and volumes of laboratory draws, with the least intensive phlebotomy practice observed in the general hospital wards. Patients in the highest quartile of cumulative blood drawn experienced the longest hospitalizations, lowest nadir hemoglobin concentrations, and greatest RBC transfusion utilization. Differences in phlebotomy practice were limited across patient age, gender, and race. Hemoglobin concentrations declined during hospitalization, congruent with intensity of phlebotomy practice. Each 100 mL of phlebotomy volume during hospitalization was associated with a 1.15 (95% confidence interval [CI], 1.14-1.17; P < .001) multiplicative increase in RBC units transfused in adjusted analyses. Estimated annual phlebotomy costs exceeded $15 million (approximately $2500 per patient admission). CONCLUSIONS: Phlebotomy continues to be a major source of blood loss in hospitalized patients with critical illness, and more intensive phlebotomy practices are associated with lower hemoglobin concentrations and greater transfusion utilization.

The Prevalence and Clinical Significance of Preoperative Thrombocytopenia in Adults Undergoing Elective Surgery: An Observational Cohort Study.

BACKGROUND: Preoperative thrombocytopenia is associated with inferior outcomes in surgical patients, though concurrent anemia may obfuscate these relationships. This investigation assesses the prevalence and clinical significance of preoperative thrombocytopenia with thorough consideration of preoperative anemia status. METHODS: This is an observational cohort study of adults undergoing elective surgery with planned postoperative hospitalization from January 1, 2009 to May 3, 2018. Patients were designated into 4 groups: normal platelet and hemoglobin concentrations, isolated thrombocytopenia (ie, platelet count <100 × 109/L), isolated anemia (ie, hemoglobin <12 g/dL women, <13.5 g/dL men), and thrombocytopenia with anemia. Thrombocytopenia was further defined as incidental (ie, previously undiagnosed) or nonincidental. Multivariable regression analyses were utilized to assess the relationships between thrombocytopenia status and clinical outcomes, with a primary outcome of hospital length of stay. RESULTS: A total of 120,348 patients were included for analysis: 72.3% (95% confidence interval [CI], 72.1-72.6) normal preoperative laboratory values, 26.3% (26.1-26.6) isolated anemia, 0.80% (0.75-0.86) thrombocytopenia with anemia, and 0.52% (0.48-0.56) isolated thrombocytopenia (0.38% [0.34-0.41] nonincidental, 0.14% [0.12-0.17] incidental). Thrombocytopenia was associated with longer hospital length of stay in those with concurrent anemia (multiplicative increase of the geometric mean 1.05 [1.00, 1.09] days; P = .034) but not in those with normal preoperative hemoglobin concentrations (multiplicative increase of the geometric mean 1.02 [0.96, 1.07] days; P = .559). Thrombocytopenia was associated with increased odds for intraoperative transfusion regardless of anemia status (nonanemic: 3.39 [2.79, 4.12]; P < .001 vs anemic: 2.60 [2.24, 3.01]; P < .001). Thrombocytopenia was associated with increased rates of intensive care unit (ICU) admission in nonanemic patients (1.56 [1.18, 2.05]; P = .002) but not in those with preoperative anemia (0.93 [0.73, 1.19]; P = .578). CONCLUSIONS: Preoperative thrombocytopenia is associated with clinical outcomes in elective surgery, both in the presence and absence of concurrent anemia. However, isolated thrombocytopenia is rare (0.5%) and is usually identified before preoperative testing. It is unlikely that routine thrombocytopenia screening is indicated for most patients.

Same-Day Cancellation in Vascular Surgery: 10-Year Review at a Large Tertiary Care Center.

BACKGROUND: Same-day cancellation of vascular surgical procedures is an undesirable occurrence with multifaceted implications into the patient's health care. Numerous factors play a role in same-day cancellations, ranging from medical causes, patient factors, or administrative and scheduling conflicts. METHODS: A retrospective review of the medical records database at our large tertiary academic referral center from 2007 to 2017 was performed to identify patients scheduled for vascular surgical procedures who experienced same-day cancellation. RESULTS: Of the 17,887 scheduled vascular surgical procedures during the study period, 361 (2%) patients experienced same-day cancellations. Seventy-five percent of cancellations were determined to be nonforeseeable, 12.5% foreseeable, and 12.5% indeterminate. The most common reasons for cancellation were medical (55%), patient-initiated cancellation (12%), procedure no longer required (10%), and administrative or scheduling conflicts (10%). Twenty-six (7.3%) patients died within 30 days after their cancelled vascular operation. Most patients (69%) eventually received the planned operation, with a mean interval of 45.5 ± 135.8 days between cancellation and performance of the aforementioned procedure. CONCLUSIONS: At our institution, same-day cancellations of vascular surgical procedures were infrequent (2%). Most cancellations were due to medical reasons. Although most cancellations were determined to be nonforeseeable, emphasizing foreseeable cancellations may provide opportunities to improve patient care, enhance satisfaction, and reduce future cancellations.

Thrombocytosis: Perioperative Considerations for Patients Undergoing Cardiac Surgery.

Thrombocytosis is an uncommon yet important laboratory abnormality with significant considerations for patients undergoing cardiac surgery. The etiology of thrombocytosis can be categorized by those related to reactive processes; acquired platelet disorders (ie, myeloproliferative neoplasms, hematologic malignancies); or inherited platelet disorders (ie, hereditary thrombocythemia). A foundational understanding of the normal physiologic function of platelets and the abnormalities associated with each of these disorders is critical when considering implications and optimization to prevent perioperative complications. This review systematically outlines the platelet disorders that cause thrombocytosis with an emphasis on how the disorder affects normal physiologic processes, summarizes the literature related to the disorder, and the describes the implications and recommendations for patients undergoing cardiac surgery.

Increasing Mortality in Venovenous Extracorporeal Membrane Oxygenation for COVID-19-Associated Acute Respiratory Distress Syndrome.

OBJECTIVES: Determine the factors associated with mortality in venovenous extracorporeal membrane oxygenation (V-V ECMO) patients with COVID-19 infection and provide an updated report of clinical outcomes for patients treated with V-V ECMO for COVID-19 in Minnesota. DESIGN: Multicenter prospective observational study. SETTING: The four adult Extracorporeal Life Support Organization-certified Centers of Excellence in Minnesota. PATIENTS: A total of 100 patients treated with V-V ECMO for COVID-19-associated acute respiratory distress syndrome (ARDS) from March 2020 to May 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 60-day survival for patients treated with V-V ECMO for COVID-19. Outcomes of patients treated from November 2020 to May 2021(cohort 2) were compared with data from a previous cohort of patients, collected from March 2020 to October 2020 (cohort 1). The data from both cohorts were merged into a single dataset (Combined Cohort). Survival on V-V ECMO due to COVID-19-associated ARDS significantly decreased after October 2020 (63% vs 41%; p = 0.026). The median interval from hospital admission to V-V ECMO cannulation was significantly associated with 60-day mortality (10 d [6-14 d] in nonsurvivors vs 7 d [4-9 d] in survivors; p = 0.001) in the Combined Cohort and was also significantly longer in cohort 2 than cohort 1 (10 d [7-14 d] vs 6 d [4-10 d]; p < 0.001). In the Combined Cohort, the 60-day survival for patients who did not receive steroids was 86% (n = 12) versus 45% (n = 39) for patients who received at least one dose of steroids (p = 0.005). CONCLUSIONS: There was a significant increase in mortality for patients treated with V-V ECMO for COVID-19-associated ARDS in cohort 2 compared with cohort 1. Further research is required to determine the cause of the worsening trend in mortality.

Nebulized Nitroglycerin for Coronavirus Disease 2019-Associated Acute Respiratory Distress Syndrome: A Case Report.

We present a case where nitroglycerin tablets dissolved in saline and intravenous nitroglycerin solution were nebulized as surrogates for inhaled nitric oxide (iNO) after our iNO supply was depleted during the coronavirus disease 2019 (COVID-19) surge in New York. We gave this treatment to a COVID-19 patient with severe acute respiratory distress syndrome (ARDS) and hypercarbia. In response, the patient had immediate and clinically meaningful improvement in multiple organ systems despite no other interventions or ventilator changes.

Resting sympathetic activity is associated with the sympathetically mediated component of energy expenditure following a meal.

Individuals with high plasma norepinephrine (NE) levels at rest have a smaller reduction in resting energy expenditure (REE) following ß-adrenergic blockade. If this finding extends to the response to a meal, it could have important implications for the role of the sympathetic nervous system in energy balance and weight gain. We hypothesized high muscle sympathetic nerve activity (MSNA) would be associated with a low sympathetically mediated component of energy expenditure following a meal. Fourteen young, healthy adults completed two visits randomized to continuous saline (control) or intravenous propranolol to achieve systemic ß-adrenergic blockade. Muscle sympathetic nerve activity and REE were measured (indirect calorimetry) followed by a liquid mixed meal (Ensure). Measures of energy expenditure continued every 30 min for 5 h after the meal and are reported as an area under the curve (AUC). Sympathetic support of energy expenditure was calculated as the difference between the AUC during saline and ß-blockade (AUCPropranolol-AUCSaline, ß-REE) and as a percent (%) of control (AUCPropranolol÷AUCSaline × 100). ß-REE was associated with baseline sympathetic activity, such that individuals with high resting MSNA (bursts/100 heart beats) and plasma NE had the greatest sympathetically mediated component of energy expenditure following a meal (MSNA: ß-REE R = -0.58, P = 0.03; %REE R = -0.56, P = 0.04; NE: ß-REE R = -0.55, P = 0.0535; %REE R = -0.54, P = 0.0552). Contrary to our hypothesis, high resting sympathetic activity is associated with a greater sympathetically mediated component of energy expenditure following a liquid meal. These findings may have implications for weight maintenance in individuals with varying resting sympathetic activity.

Acute effects of a mixed meal on arterial stiffness and central hemodynamics in healthy adults.

BACKGROUND: Elevated central pressures and arterial stiffness are associated with increased peripheral resistance and higher sympathetic nervous system activity. Additionally, consumption of a meal is known to be sympathoexcitatory. However, the acute effects of a meal on aortic wave reflection and stiffness are unknown. Therefore, we tested the hypothesis that aortic wave reflection and stiffness would increase after a meal. METHODS: We examined these effects using high-fidelity radial arterial pressure waveforms and carotid-femoral pulse wave velocity measured noninvasively by applanation tonometry before and 60 and 180 minutes after ingestion of a liquid mixed meal (Ensure; 40% of daily energy expenditure) in 17 healthy adults (9 men/8 women; aged 29 ± 2 years). Additionally, we measured sympathetic activity by microneurography at baseline and up to 60 minutes after the meal. RESULTS: Although sympathetic activity increased after the meal, both peripheral and central pressures were reduced at 180 minutes from baseline (all P < 0.05). Contrary to our hypothesis, augmentation index (14% ± 3% vs. 2% ± 3% vs. 8% ± 3%), augmentation index normalized for heart rate (8% ± 3% vs. -3% ± 3% vs. 3% ± 3%), augmented pressure (5 ± 1 mm Hg vs. 1 ± 1 mm Hg vs. 3 ± 1 mm Hg), and pulse wave velocity (7.1 ± 0.2 m/s vs. 6.7 ± 0.2 m/s vs. 6.7 ± 0.1 m/s) were substantially reduced at 60 and 180 minutes after the meal (all P < 0.05). CONCLUSIONS: Taken together, our results suggest that a liquid mixed meal acutely decreases central hemodynamics and arterial stiffness in healthy adults, which may be a result of meal-related increases in insulin and/or visceral vasodilation.

Acute cyclooxygenase inhibition does not alter muscle sympathetic nerve activity or forearm vasodilator responsiveness in lean and obese adults.

Obesity is often characterized by chronic inflammation that may contribute to increased cardiovascular risk via sympathoexcitation and decreased vasodilator responsiveness. We hypothesized that obese individuals would have greater indices of inflammation compared with lean controls, and that cyclooxygenase inhibition using ibuprofen would reduce muscle sympathetic nerve activity (MSNA) and increase forearm blood flow in these subjects. We measured MSNA, inflammatory biomarkers (C-reactive protein [CRP] and Interleukin-6 [IL-6]), and forearm vasodilator responses to brachial artery acetylcholine and sodium nitroprusside in 13 men and women (7 lean; 6 obese) on two separate study days: control (CON) and after 800 mg ibuprofen (IBU). CRP (1.7 ± 0.4 vs. 0.6 ± 0.3 mg/L; P < 0.05) and IL-6 (4.1 ± 1.5 vs. 1.0 ± 0.1pg/mL; P < 0.05) were higher in the obese group during CON and tended to decrease with IBU (IL-6: P < 0.05; CRP: P = 0.14). MSNA was not different between groups during CON (26 ± 4 bursts/100 heart beats (lean) versus 26 ± 4 bursts/100 heart beats (obese); P = 0.50) or IBU (25 ± 4 bursts/100 heart beats (lean) versus 30 ± 5 bursts/100 heart beats (obese); P = 0.25), and was not altered by IBU. Forearm vasodilator responses were unaffected by IBU in both groups. In summary, an acute dose of ibuprofen did not alter sympathetic nerve activity or forearm blood flow responses in healthy obese individuals, suggesting that the cyclooxygenase pathway is not a major contributor to these variables in this group.

Association of cardiac baroreflex sensitivity with blood pressure transients: influence of sex and menopausal status.

The magnitude of decrease in blood pressure (BP) during a vasoactive drug bolus may be associated with the calculated baroreflex sensitivity (BRS). The purpose of the present study was to evaluate whether sympathetic and/or cardiac BRS relates to the extent of change in BP and whether this was altered by sex hormones. Fifty-one young women (27 ± 1 years), 14 older women (58 ± 1 years), and 36 young men (27 ± 1 years) were studied. Heart rate, BP, and muscle sympathetic nerve activity (MSNA) were monitored. Sympathetic BRS was analyzed using the slope of the MSNA-diastolic blood pressure (DBP) relationship and cardiac BRS was analyzed using the R-R interval-systolic blood pressure (SBP) relationship. Young women and men had similar mean arterial pressures (MAP, 91 ± 1 vs. 90 ± 1 mmHg), cardiac BRS (19 ± 1 vs. 21 ± 2 ms/mmHg), and sympathetic BRS (-6 ± 1 vs. -7 ± 1 AU/beat/mmHg), respectively. Older women had higher MAP (104 ± 4 mmHg, p < 0.05) and lower cardiac BRS (7 ± 1 ms/mmHg, p < 0.05), but similar sympathetic BRS (-8 ± 1 AU/beat/mmHg). There was no association between BP transients with either cardiac or sympathetic BRS in young women. In the older women, the drop in SBP, DBP, and MAP were associated with cardiac BRS (r = 0.60, r = 0.59, and r = 0.70, respectively; p < 0.05), but not sympathetic BRS. The decrease in SBP was positively related to cardiac BRS in young men (r = 0.41; p < 0.05). However, there was no relationship between the decrease in BP and sympathetic BRS. This indicates that older women and young men with low cardiac BRS have larger transients in BP during nitroprusside. This suggests a more prominent role for cardiac (as opposed to sympathetic) BRS in responding to acute BP changes in young men and older women. The fact that these relationships do not exist in young women suggest that the female sex hormones influence baroreflex responses.