Matthew Sharron

Platelets induce apoptosis during sepsis in a contact-dependent manner that is inhibited by GPIIb/IIIa blockade.

Purpose End-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS), especially where platelets accumulate (e.g. spleen and lung). We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s) of and mechanism(s) by which platelet granzyme B induces end-organ apoptosis in sepsis. Methods End-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis) was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score. Measurements and Main Results There was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (pu200a=u200a0.008). Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice. Conclusions In sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis.

Use of the pediatric intensive care unit for post-procedural monitoring in young children following microlaryngobronchoscopy: Impact on resource utilization and hospital cost

OBJECTIVEnTo assess the frequency of post-procedural complications, medical interventions, and hospital costs associated with microlaryngobronchoscopy (MLB) in children prophylactically admitted for pediatric intensive care unit (PICU) monitoring for ageu202f≤u202f2 years.nnnMETHODSnWe performed a single-center, retrospective, descriptive study within a 44-bed PICU in a stand-alone, tertiary, pediatric referral center. Inclusion criteria were age ≤2 years and pre-procedural selection of prophylactic PICU monitoring after MLB between January 2010 and December 2015. Children were excluded for existing tracheostomy, if undergoing concurrent non-otolaryngeal procedures, or if intubated at the time of PICU admission. Primary outcomes were the development of major and minor procedural complications and medical rescue interventions. Secondary outcomes were hospital cost and length of stay (LOS).nnnRESULTSnOne hundred and eight subjects met inclusion criteria with a median age of 5.3 (IQR: 2.6-10.9) months. A majority (86%) underwent therapeutic instrumentation in addition to diagnostic MLB. There were no observed major complications or rescue interventions. Minor complications were noted within 5u202fh of monitoring and included isolated stridor (24%), desaturation <90% (10%), and nausea/emesis (8%). Minor interventions included supplemental oxygen via regular nasal cannula (39%), single-dose inhaled racemic epinephrine (19%), single-dose systemic corticosteroids (19%), or high flow nasal cannula (HFNC) therapy (4%). Save for two cases of HFNC, interventions were completed or discontinued within 5u202fh. Median PICU LOS was 1.1 days and median cost was

Early initiation of inhaled corticosteroids does not decrease acute chest syndrome morbidity in pediatric patients with sickle cell disease

9650 (IQR:

571: VENOUS THROMBOEMBOLISM IN CRITICALLY ILL CHILDREN WITH CARDIAC DISEASE

8235-

572: THYMIC HEMORRHAGE PRESENTING AS AN ANTERIOR MEDIASTINAL MASS IN AN INFANT WITH VITAMIN K DEFICIENCY

14,861) per encounter. Estimated cost of same day observation in our post anesthesia care unit (PACU) following MLB without PICU admission is

1516: SEVERE COMPLICATIONS AND ICU INTERVENTIONS ARE RARE IN YOUNG CHILDREN AFTER MICROLARYNGOBRONCHOSCOPY

1921 per encounter.nnnCONCLUSIONSnIn childrenu202f≤u202f2 years of age prophylactically admitted for PICU observation, we did not observe severe complications or major interventions after MLB. Minor interventions and complications were noted early during post-procedural monitoring. PICU monitoring was substantially more expensive than same-day PACU observation. Young age as the sole criteria for prophylactic PICU monitoring after diagnostic or therapeutic MLB may be unjustified when comparable, cost-conscious care can be achieved in a PACU setting. Prior to pre-procedural selection of PICU monitoring, we recommend a broad contextual risk assessment including a review of comorbidities, operative plan, and intended anesthetic exposure.

387: CHARACTERISTICS AND OUTCOMES OF CHILDREN WITH ACUTE CHEST SYNDROME AT A CHILDREN’S HOSPITAL ICU

Acute chest syndrome (ACS) is a leading cause of mortality in patients with sickle cell disease (SCD). Systemic corticosteroids decrease ACS severity, but the risk of readmission for vaso-occlusive crises (VOC) has limited their use. The efficacy of inhaled corticosteroids (ICS) as a safer alternative is currently unknown. An observational, historic cohort study compared patients with SCD with ACS who received ICS at admission (ICS) to those who did not (non-ICS). Outcome measures included rates of transfusion, oxygen requirement, BiPAP initiation, PICU transfer, intubation, readmission, hospital cost, and length of stay. One hundred twenty patients with SCD (55 non-ICS, 65 ICS) were included. A significantly higher proportion of the non-ICS group had bilateral infiltrates, but fewer had asthma. More children in the ICS group had BiPAP initiated, however transfer to the PICU, intubation, transfusion rates, oxygen requirement, hospital cost, length of stay, and readmission rates did not differ between groups. Regression analysis did not reveal any differences in outcomes, nor were outcomes changed when patients were separated based on the presence or absence of asthma. In this observational cohort study, ICS did not demonstrate a significant reduction in ACS morbidity, though ICS use should be studied in a prospective manner.