Mannitol and Hypertonic Saline Reduce Swelling and Modulate Inflammatory Markers in a Rat Model of Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) leaves most survivors dependent at follow-up. The importance of promoting M2-like microglial responses is increasingly recognized as a key element to ameliorate brain injury following ICH. The osmotherapeutic agents, mannitol and hypertonic saline (HTS), which are routinely used to reduce intracranial pressure, have been shown to reduce neuroinflammation in experimental ischemic and traumatic brain injury, but anti-inflammatory effects of osmotherapies have not been investigated in ICH. METHODS: We studied the effects of iso-osmotic mannitol and HTS in rat models of ICH utilizing high-dose and moderate-dose collagenase injections into the basal ganglia, associated with high and low mortality, respectively. We studied the effects of osmotherapies, first given 5 h after ICH induction, and then administered every 12 h thereafter (4 doses total). Immunohistochemistry was used to quantify microglial activation and polarization. RESULTS: Compared to controls, mannitol and HTS increased plasma osmolarity 1 h after infusion (301 ± 1.5, 315 ± 4.2 and 310 ± 2.0 mOsm/kg, respectively), reduced mortality at 48 h (82, 36 and 53%, respectively), and reduced hemispheric swelling at 48 h (32, 21, and 17%, respectively). In both perihematomal and contralateral tissues, mannitol and HTS reduced activation of microglia/macrophages (abundance and morphology of Iba1 + cells), and in perihematomal tissues, they reduced markers of the microglia/macrophage M1-like phenotype (nuclear p65, TNF, and NOS2), increased markers of the microglia/macrophage M2-like phenotype (arginase, YM1, and pSTAT3), and reduced infiltration of CD45 + cells. CONCLUSIONS: Repeated dosing of osmotherapeutics at regular intervals may be a useful adjunct to reduce neuroinflammation following ICH.

Biomarkers as outcome predictors in subarachnoid hemorrhage--a systematic review.

CONTEXT: Subarachnoid hemorrhage (SAH) has a high fatality rate and many suffer from delayed neurological deficits. Biomarkers may aid in the identification of high-risk patients, guide treatment/management and improve outcome. OBJECTIVE: The aim of this review was to summarize biomarkers of SAH associated with outcome. METHODS: An electronic database query was completed, including an additional review of reference lists to include all potential human studies. RESULTS: A total of 298 articles were identified; 112 were reviewed; 55 studies were included. CONCLUSION: This review details biomarkers of SAH that correlate with outcome. It provides the basis for research investigating their possible translation into the management of SAH patients.

Impact of Pandemic Response on Training Experience of Anesthesiology Residents in an Academic Medical Center: A Retrospective Cohort Study.

Background The impact of the coronavirus disease 2019 (COVID-19) pandemic substantially altered operations at hospitals that support graduate medical education. We examined the impact of the pandemic on an anesthesiology training program with respect to overall case volume, subspecialty exposure, procedural skill experience, and approaches to airway management. Methods Data for this single center, retrospective cohort study came from an Institutional Review Board approved repository for clinical data. Date ranges were divided into the following phases in 2020: Pre-Pandemic (PP), Early Pandemic (EP), Recovery 1 (R1), and Recovery 2 (R2). All periods were compared to the same period from 2019 for case volume, anesthesia provider type, trainee exposure to Accreditation Council for Graduate Medical Education (ACGME) index case categories, airway technique, and patient variables. Results 15,087 cases were identified, with 5,598 (37.6%) in the PP phase, 1,570 (10.5%) in the EP phase, 1,451 (9.7%) in the R1 phase, and 6,269 (42.1%) in the R2 phase. There was a significant reduction in case volume during the EP phase compared to the corresponding period in 2019 (-55.3%; P < .001) that improved but did not return to baseline by the R2 phase (-17.6%; P < .001). ACGME required minimum cases were reduced during the EP phase compared to 2019 data for pediatric cases (age < 12 y, -72.1%; P < .001 and age < 3 y, -53.5%; P < .006) and cardiopulmonary bypass cases (52.3%, P < .003). Surgical subspecialty case volumes were significantly reduced in the EP phase except for transplant surgery. By the R2 phase, all subspecialty volumes had recovered except for plastic surgery (14.9 vs. 10.5 cases/week; P < .006) and surgical endoscopy (59.2 vs. 40 cases/week; P < .001). Use of video laryngoscopy (VL) and rapid sequence induction and intubation (RSII) also increased from the PP to the EP phase (24.6 vs. 79.6%; P < .001 and 10.3 vs. 52.3%; P < .001, respectively) and remained elevated into the R2 phase (35.2%; P < 0.001 and 23.1%; P < .001, respectively). Conclusions The COVID-19 pandemic produced significant changes in surgical case exposure for a relatively short period. The impact was short-lived, with sufficient remaining time to meet the annual ACGME program minimum case requirements and procedural experiences. The longer-term impact may be a shift towards the increased use of VL and RSII, which became more prevalent during the early phase of the pandemic.

Systemic inflammatory response does not correlate with acute lung injury associated with mechanical ventilation strategies in normal lungs.

BACKGROUND: Mechanical ventilation (MV) can lead to ventilator-induced lung injury secondary to trauma and associated increases in pulmonary inflammatory cytokines. There is controversy regarding the associated systemic inflammatory response. In this report, we demonstrate the effects of MV on systemic inflammation. METHODS: This report is part of a previously published study (Hong et al. Anesth Analg 2010;110:1652-60). Female pigs were randomized into 3 groups. Group H-Vt/3 was ventilated with a tidal volume (Vt) of 15 mL/kg predicted body weight (PBW)/positive end-expiratory pressure (PEEP) of 3 cm H(2)O; group L-Vt/3 with a Vt of 6 mL/kg PBW/PEEP of 3 cm H2O; and group L-Vt/10 with a Vt of 6 mL/kg PBW/PEEP of 10 cm H(2)O, for 8 hours. Each group had 6 subjects (n = 6). Prelung and postlung sera were analyzed for inflammatory markers. Hemodynamics, airway mechanics, and arterial blood gases were monitored. RESULTS: There were no significant differences in systemic cytokines among groups. There were similar trends of serum inflammatory markers in all subjects. This is in contrast to findings previously published demonstrating increases in inflammatory mediators in bronchoalveolar lavage. CONCLUSION: Systemic inflammatory markers did not correlate with lung injury associated with MV.

Low tidal volume and high positive end-expiratory pressure mechanical ventilation results in increased inflammation and ventilator-associated lung injury in normal lungs.

BACKGROUND: Protective mechanical ventilation with low tidal volume (Vt) and low plateau pressure reduces mortality and decreases the length of mechanical ventilation in patients with acute respiratory distress syndrome. Mechanical ventilation that will protect normal lungs during major surgical procedures of long duration may improve postoperative outcomes. We performed an animal study comparing 3 ventilation strategies used in the operating room in normal lungs. We compared the effects on pulmonary mechanics, inflammatory mediators, and lung tissue injury. METHODS: Female pigs were randomized into 3 groups. Group H-Vt/3 (n = 6) was ventilated with a Vt of 15 mL/kg predicted body weight (PBW)/positive end-expiratory pressure (PEEP) of 3 cm H(2)O, group L-Vt/3 (n = 6) with a Vt of 6 mL/kg PBW/PEEP of 3 cm H(2)O, and group L-Vt/10 (n = 6) with a Vt of 6 mL/kg PBW/PEEP of 10 cm H(2)O, for 8 hours. Hemodynamics, airway mechanics, arterial blood gases, and inflammatory markers were monitored. Bronchoalveolar lavage (BAL) was analyzed for inflammatory markers and protein concentration. The right lower lobe was assayed for mRNA of specific cytokines. The right lower lobe and right upper lobe were evaluated histologically. RESULTS: In contrast to groups H-Vt/3 and L-Vt/3, group L-Vt/10 exhibited a 6-fold increase in inflammatory mediators in BAL (P < 0.001). Cytokines in BAL were similar in groups H-Vt/3 and L-Vt/3. Group H-Vt/3 had a significantly lower lung injury score than groups L-Vt/3 and L-Vt/10. CONCLUSION: Comparing intraoperative strategies, ventilation with high PEEP resulted in increased production of inflammatory markers. Low PEEP resulted in lower levels of inflammatory markers. High Vt/low PEEP resulted in less histologic lung injury.

Anesthetic Implications of an Obstetric Patient with Blue Rubber Bleb Nevus Syndrome.

Blue rubber bleb nevus syndrome, a syndrome of multifocal venous malformations, has been reported rarely during pregnancy. This syndrome has been associated with airway lesions in some patients and neuraxial abnormalities in other patients. We report the anesthetic and obstetric management of a patient with an extensive distribution of both airway and neuraxial lesions.

Focused comprehensive, quantitative, functionally based echocardiographic evaluation in the critical care unit is feasible and impacts care.

OBJECTIVES: To determine whether comprehensive quantitative echocardiogram could be used as a resuscitation tool in critically ill surgical patients and to assess its effect on patient care. DESIGN: Prospective observational. SETTING: The Trauma and Surgical Intensive Care Units of the University of Maryland Medical Center. PATIENTS: Critically ill trauma and surgical patients. INTERVENTIONS: The Focused Rapid Echocardiographic Evaluation (FREE), an abbreviated version of a comprehensive transthoracic echocardiogram, which is under an approved protocol, was performed. MEASUREMENTS AND MAIN RESULTS: Over a 30-month period, 791 FREEs were performed on 659 patients. The mean patient age was 60 (±17) years. Ninety-one percent were intubated and 80% were postoperative. Ejection fraction was reported for 95%, and cardiac index was reported for 89% of FREE studies. Right heart function was assessed for 94%. Measures of volume status--internal left ventricular diameter, inferior vena cava diameter, diameter change, and stroke volume variation--were reported for 88%, 79%, 75%, and 89% of patients, respectively. The FREE was judged to be useful by the consulting primary care team for 95% of patients, and altered the plan of care for 57%. The most common change was administration of a fluid bolus (43%), followed by change from an original prestudy plan to one of monitoring (24%), diuresis (23%), addition/titration of an inotropic agent (19%), and/or addition/titration of a vasoconstrictor (8%). CONCLUSIONS: The FREE is feasible and alters care in the intensive care unit by providing clinical data not otherwise available at the bedside. Further studies are warranted to assess the impact of comprehensive echocardiogram-directed resuscitation on patient outcomes.

Patients with chronic pulmonary disease.

Chronic pulmonary disease is common among the surgical population and the importance of a thorough and detailed preoperative assessment is monumental for minimizing morbidity and mortality and reducing the risk of perioperative pulmonary complications. These comorbidities contribute to pulmonary postoperative complications, including atelectasis, pneumonia, and respiratory failure, and can predict long-term mortality. The important aspects of the preoperative assessment for patients with chronic pulmonary disease, and the value of preoperative testing and smoking cessation, are discussed. Specifically discussed are preoperative pulmonary assessment and management of patients with chronic obstructive pulmonary disease, asthma, restrictive lung disease, obstructive sleep apnea, and obesity.

Practical considerations for the dosing and adjustment of continuous renal replacement therapy in the intensive care unit.

Familiarity with the initiation, dosing, adjustment, and termination of continuous renal replacement therapy (CRRT) is a core skill for contemporary intensivists. Guidelines for how to administer CRRT in the intensive care unit are not well documented. The purpose of this review is to discuss the modalities, terminology, and components of CRRT, with an emphasis on the practical aspects of dosing, adjustments, and termination. Management of electrolyte and acid-base derangements commonly encountered with acute renal failure is emphasized. Knowledge regarding the practical aspects of managing CRRT in the intensive care unit is a prerequisite for achieving desired physiological end points.

Arrested natural killer cell development associated with transgene insertion into the Atf2 locus.

Natural killer (NK) cell development in the bone marrow is not fully understood. Following lineage commitment, these cells appear to advance through a series of developmental stages that are beginning to be characterized. We previously reported a selective deficiency of NK cells in a C57BL/6 mouse with a transgenic construct consisting of the cDNA for the Ly49A major histocompatibility complex (MHC) class 1-specific inhibitory receptor driven by the granzyme A gene. This mouse has few NK cells in peripheral tissues with relative preservation of other immune cells, including T and B cells. Herein we demonstrate that these mice have an accumulation of NK cells with an immature phenotype in the bone marrow, consistent with a block at a previously proposed stage in normal NK-cell development. The phenotype is associated with transgenic insertion into Atf2, the gene for the basic leucine zipper (bZIP) transcription factor family member ATF-2. Although analysis of Atf2-null NK cells shows no defect, the transgenic mice express abnormal truncated Atf2 transcripts that may mediate a repressor effect because ATF2 can heterodimerize with other bZIP molecules. The defect is cell intrinsic, suggesting that certain bZIP molecules play significant roles in NK-cell development.