Matzek, Luke J.

AbstractBackgroundEvaluations 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.MethodsThis 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.Results2433 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%).DiscussionThe 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%.

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.

Abstract 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.

Baroreflex sensitivity is calculated from the slope of the relationship between blood pressure and muscle sympathetic nerve activity (MSNA) or cardiac R‐R interval. The magnitude of decrease in blood pressure during a vasoactive drug bolus (i.e. modified Oxford) to test the baroreflex may be associated with the calculated baroreflex sensitivity (BRS) slope. We investigated whether the cardiac or sympathetic BRS are associated with the acute decrease in blood pressure during a modified Oxford in young healthy men and women. Forty‐five women (27 ± 1 yrs, BMI 22.9 ± 0.3 kg/m2) and 30 men (27 ± 1 yrs, 24.2 ± 0.4 kg/m2) were studied. MSNA was measured via peroneal microneurography and blood pressure was measured with a brachial intraarterial catheter. Women and men had similar mean arterial pressures (91 ± 1 vs. 90 ± 1 mmHg), cardiac BRS (19 ± 1 vs. 21 ± 2 ms/mmHg), and sympathetic BRS (−6 ± 0.4 vs. −7 ± 0.6 AU/beat/mmHg), respectively. The decrease in systolic blood pressure (SBP) and pulse pressure (PP) was positively related to cardiac BRS in men (r=.47; p<0.01; r=.49; p<0.01). However, there was no relationship between the decrease in blood pressure and sympathetic BRS in men. In addition, there was no association between any blood pressure transients with either cardiac or sympathetic BRS in women. Our results suggest the magnitude of decrease in blood pressure is associated with cardiac BRS in men, but not women. Funded by NIH

The thermic effect of food (TEF) is partially mediated by β‐adrenergic receptors (βAR) and is an important component of daily energy expenditure. Greater sympathetic activity has been associated with decreased BAR responsiveness. We hypothesized that muscle sympathetic nerve activity (MSNA) would be inversely correlated with the βAR component of TEF (TEF β ). We measured MSNA (microneurography) and energy expenditure (EE) (indirect calorimetry) before and for 5 h after a mixed meal (40% daily EE). Measurements were made during systemic βAR blockade with propranolol (BB) and saline (NS) infusion on separate days in 10 healthy subjects (2 female, age 28±2 y, BMI 24.4±0.6 kg/m 2 ). Resting MSNA was 39±3 bursts/100 heartbeats (hb). Within 1 h after the meal, MSNA significantly increased during both NS (12±3 bursts/100 hb) and BB (18±4) but was not significantly different between the two days, (P=0.375). The maximum increase in REE after the meal was 269±29 (NS) and 198±22 (BB) kcal/24 h (P<0.05). TEF β (TEF β = AUC TEF NS – AUC TEF BB ) was 48±20% of total TEF. TEF β was positively correlated with resting MSNA (R 2 =0.70, P<0.05). Contrary to our hypothesis, we found that greater levels of MSNA were associated with greater TEF β . These results indicated that resting MSNA may be an important contributor to daily energy expenditure. Studies are needed to determine if greater MSNA is associated with a resistance to weight gain. The project described was supported by the Mayo Foundation for Medical Education and Research and NIH Grant Numbers K23 DK82424, P30 DK50456, and UL1 RR024150.

Elevated central hemodynamics 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 following a meal. We examined these effects using high‐fidelity radial arterial pressure waveforms and carotid‐femoral pulse wave velocity (PWV), measured non‐invasively via applanation tonometry, before and 60 and 180 min after ingestion of a liquid mixed meal (Ensure, 40% of daily energy expenditure) in 15 healthy adults (25 ± 2 y; 8M/7F). Both peripheral and central pressures were reduced 180 min from baseline. Yet contrary to our hypothesis, augmentation index (15 ± 4 vs. 2 ± 3 vs. 8 ± 3%), augmentation index normalized for heart rate (9 ± 4 vs. −2 ± 3 vs. 3 ± 3%), augmented pressure (6 ± 2 vs. 1 ± 1 vs. 3 ± 1 mmHg) as well as carotid‐femoral PWV (7.3 ± 0.2 vs. 6.7 ± 0.2 vs. 6.7 ± 0.1 m/s) were substantially reduced at 60 and 180 min following the meal (P < 0.05 for all). Taken together, our results suggest that a liquid mixed meal acutely decreases central hemodynamics and arterial stiffness in healthy adults. NIH K23 DK82424 (TC) P30 DK50456 (MNOC) UL1 RR024150 (MCCTSA) HL105467 (DPC)

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.

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 × 10 9 /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.