Lung Protective Ventilation during Pregnancy: An Observational Cohort Study.

Objectives We sought to describe characteristics of mechanically ventilated pregnant patients, evaluate utilization of low-tidal-volume ventilation (LTVV) and high-tidal-volume ventilation (HTVV) by trimester, and describe maternal and fetal outcomes by ventilation strategy. Study Design This is a retrospective cohort study of pregnant women with mechanical ventilation for greater than 24 hours between July 2012 and August 2020 at a tertiary care academic medical center. We defined LTVV as average daily tidal volume 8 mL/kg of less of predicted body weight, and HTVV as greater than 8 mL/kg. We examined demographic characteristics, maternal and fetal characteristics, and outcomes by ventilation strategy. Results We identified 52 ventilated pregnant women, 43 had LTVV, and 9 had HTVV. Acute respiratory distress syndrome occurred in 73% ( N = 38) of patients, and infection was a common indication for ventilation ( N = 33, 63%). Patients had LTVV more often than HTVV in all trimesters. Obstetric complications occurred frequently, 21% ( N = 11) experienced preeclampsia or eclampsia, and among 43 patients with available delivery data, 60% delivered preterm ( N = 26) and 16% had fetal demise ( N = 7). Conclusion LTVV was utilized more often than HTVV among pregnant women in all trimesters. There was a high prevalence of maternal and fetal morbidity and fetal mortality among our cohort. Key Points Our center utilized low tidal more often than high-tidal-volume ventilation during all trimesters of pregnancy.Prone positioning can be performed at advanced gestations.Infection is a common cause of antepartum ventilation.

Improving delivery of low tidal volume ventilation in 10 ICUs.

Low tidal volume ventilation (LTVV) is standard of care for mechanically ventilated patients with acute respiratory distress syndrome and has been shown to improve outcomes in the general mechanically ventilated population. Despite these improved outcomes, in clinical practice the LTVV standard of care is often not met. We aimed to increase compliance with LTVV in mechanically ventilated patients in 10 intensive care units at 3 hospitals within the University of Pittsburgh School of Medicine Department of Critical Care Medicine. Four Plan-Do-Study-Act (PDSA) cycles were implemented to improve compliance with LTVV. Initial compliance rates of 40.6%-60.1% improved to 91%-96% by the end of the fourth PDSA cycle. The most impactful step in the intervention was providing education and giving responsibility of selecting the tidal volume to the respiratory therapist. The overall intervention resulted in improved compliance with LTVV that has been sustained for multiple years after our active PDSA cycles.

Effects of aged stored autologous red blood cells on human plasma metabolome.

Cold storage of blood for 5 to 6 weeks has been shown to impair endothelial function after transfusion and has been associated with measures of end-organ dysfunction. Although the products of hemolysis, such as cell-free plasma hemoglobin, arginase, heme, and iron, in part mediate these effects, a complete analysis of transfused metabolites that may affect organ function has not been evaluated to date. Blood stored for either 5 or 42 days was collected from 18 healthy autologous volunteers, prior to and after autologous transfusion into the forearm circulation, followed by metabolomics analyses. Significant metabolic changes were observed in the plasma levels of hemolytic markers, oxidized purines, plasticizers, and oxidized lipids in recipients of blood stored for 42 days, compared with 5 days. Notably, transfusion of day 42 red blood cells (RBCs) increased circulating levels of plasticizers (diethylhexyl phthalate and derivatives) by up to 18-fold. Similarly, transfusion of day 42 blood significantly increased circulating levels of proinflammatory oxylipins, including prostaglandins, hydroxyeicosatrienoic acids (HETEs), and dihydroxyoctadecenoic acids. Oxylipins were the most significantly increasing metabolites (for 9-HETE: up to ∼41-fold, P = 3.7e-06) in day 42 supernatants. Measurements of arginine metabolism confirmed an increase in arginase activity at the expense of nitric oxide synthesis capacity in the bloodstream of recipients of day 42 blood, which correlated with measurements of hemodynamics. Metabolic changes in stored RBC supernatants impact the plasma metabolome of healthy transfusion recipients, with observed increases in plasticizers, as well as vasoactive, pro-oxidative, proinflammatory, and immunomodulatory metabolites after 42 days of storage.

Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function.

RATIONALE: A major abnormality that characterizes the red cell "storage lesion" is increased hemolysis and reduced red cell lifespan after infusion. Low levels of intravascular hemolysis after transfusion of aged stored red cells disrupt nitric oxide (NO) bioavailabity, via accelerated NO scavenging reaction with cell-free plasma hemoglobin. The degree of intravascular hemolysis post-transfusion and effects on endothelial-dependent vasodilation responses to acetylcholine have not been fully characterized in humans. OBJECTIVES: To evaluate the effects of blood aged to the limits of Food and Drug Administration-approved storage time on the human microcirculation and endothelial function. METHODS: Eighteen healthy individuals donated 1 U of leukopheresed red cells, divided and autologously transfused into the forearm brachial artery 5 and 42 days after blood donation. Blood samples were obtained from stored blood bag supernatants and the antecubital vein of the infusion arm. Forearm blood flow measurements were performed using strain-gauge plethysmography during transfusion, followed by testing of endothelium-dependent blood flow with increasing doses of intraarterial acetylcholine. MEASUREMENTS AND MAIN RESULTS: We demonstrate that aged stored blood has higher levels of arginase-1 and cell-free plasma hemoglobin. Compared with 5-day blood, the transfusion of 42-day packed red cells decreases acetylcholine-dependent forearm blood flows. Intravascular venous levels of arginase-1 and cell-free plasma hemoglobin increase immediately after red cell transfusion, with more significant increases observed after infusion of 42-day-old blood. CONCLUSIONS: We demonstrate that the transfusion of blood at the limits of Food and Drug Administration-approved storage has a significant effect on the forearm circulation and impairs endothelial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01137656).

Nonalcoholic Wernicke's Encephalopathy Associated with Unintentional Weight Loss, Cholecystectomy, and Intractable Vomiting: The Role of Dual Thiamine and Corticosteroid Therapy.

A 23-year-old male with one month of intractable vomiting, subsequent cholecystitis status post cholecystectomy, and overall 40-pound weight loss over the last few months presented with altered mental status and seizures. MRI showed signal abnormalities involving the hypothalamus, periaqueductal gray matter, 4th ventricle, and bilateral thalami, indicative of Wernicke's encephalopathy. The patient was started on empiric IV thiamine and methylprednisolone; thiamine levels were subsequently found to be low. Infectious disease workup was negative. Within a few days of this therapy, the patient's neurological status steadily improved with increased responsiveness and communication. Repeat MRI 7 days after admission showed significant resolution of the signal abnormalities. Over the next several weeks the patient became fully conversational, cognitively intact, and increasingly ambulatory. Nonalcoholic Wernicke's encephalopathy is rare; there have been reports relating it separately to vomiting and invasive surgery. In this case report, we associate it with both recurrent vomiting and minimally invasive cholecystectomy. We also discuss combinatorial therapy of thiamine and corticosteroids, which is poorly defined in the literature. Though there is no consensus-based optimal treatment of Wernicke's encephalopathy, this adds to the discussion of using dual therapy and supports that the use of empiric corticosteroids does not harm the patient.

Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesion.

BACKGROUND: Intravascular red cell hemolysis impairs nitric oxide (NO)-redox homeostasis, producing endothelial dysfunction, platelet activation, and vasculopathy. Red blood cell storage under standard conditions results in reduced integrity of the erythrocyte membrane, with formation of exocytic microvesicles or microparticles and hemolysis, which we hypothesized could impair vascular function and contribute to the putative storage lesion of banked blood. METHODS AND RESULTS: We now find that storage of human red blood cells under standard blood banking conditions results in the accumulation of cell-free and microparticle-encapsulated hemoglobin, which, despite 39 days of storage, remains in the reduced ferrous oxyhemoglobin redox state and stoichiometrically reacts with and scavenges the vasodilator NO. Using stopped-flow spectroscopy and laser-triggered NO release from a caged NO compound, we found that both free hemoglobin and microparticles react with NO about 1000 times faster than with intact erythrocytes. In complementary in vivo studies, we show that hemoglobin, even at concentrations below 10 µmol/L (in heme), produces potent vasoconstriction when infused into the rat circulation, whereas controlled infusions of methemoglobin and cyanomethemoglobin, which do not consume NO, have substantially reduced vasoconstrictor effects. Infusion of the plasma from stored human red blood cell units into the rat circulation produces significant vasoconstriction related to the magnitude of storage-related hemolysis. CONCLUSIONS: The results of these studies suggest new mechanisms for endothelial injury and impaired vascular function associated with the most fundamental of storage lesions, hemolysis.