American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock.

OBJECTIVES: The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine "Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock." DESIGN: Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006-2014). The PubMed/Medline/Embase literature (2006-14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. MEASUREMENTS AND MAIN RESULTS: The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. CONCLUSIONS: The major new recommendation in the 2014 update is consideration of institution-specific use of 1) a "recognition bundle" containing a trigger tool for rapid identification of patients with septic shock, 2) a "resuscitation and stabilization bundle" to help adherence to best practice principles, and 3) a "performance bundle" to identify and overcome perceived barriers to the pursuit of best practice principles.

Improving Integration of Basic Science into Clinical Medicine: Vertical Integration into Clinical Education (VICE) Activity.

The integration of basic science into clinical clerkships continues to be a challenge in medical curricula. We developed an integrated session for 3rd year medical students enrolled in OB-Gyn/Pediatric Block. The session focused on transplacental and perinatal infections, and consisted of a student-driven pedagogy activity in which students were required to explain the basic science principles behind the pathophysiology of the clinical presentations, the work-up, and the treatment of the infections. This approach helps students understand how basic science knowledge informs clinical practice and potential increase clerkship-level students' confidence as it makes them serve as leaders of active learning modules. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01485-7.

Multicenter cohort study of out-of-hospital pediatric cardiac arrest.

OBJECTIVES: To describe a large cohort of children with out-of-hospital cardiac arrest with return of circulation and to identify factors in the early postarrest period associated with survival. These objectives were for planning an interventional trial of therapeutic hypothermia after pediatric cardiac arrest. METHODS: A retrospective cohort study was conducted at 15 Pediatric Emergency Care Applied Research Network clinical sites over an 18-month study period. All children from 1 day (24 hrs) to 18 yrs of age with out-of-hospital cardiac arrest and a history of at least 1 min of chest compressions with return of circulation for at least 20 mins were eligible. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-eight cases met study entry criteria; the overall mortality was 62% (85 of 138 cases). The event characteristics associated with increased survival were as follows: weekend arrests, cardiopulmonary resuscitation not ongoing at hospital arrival, arrest rhythm not asystole, no atropine or NaHCO3, fewer epinephrine doses, shorter duration of cardiopulmonary resuscitation, and drowning or asphyxial arrest event. For the 0- to 12-hr postarrest return-of-circulation period, absence of any vasopressor or inotropic agent (dopamine, epinephrine) use, higher lowest temperature recorded, greater lowest pH, lower lactate, lower maximum glucose, and normal pupillary responses were all associated with survival. A multivariate logistic model of variables available at the time of arrest, which controlled for gender, age, race, and asystole or ventricular fibrillation/ventricular tachycardia anytime during the arrest, found the administration of atropine and epinephrine to be associated with mortality. A second model using additional information available up to 12 hrs after return of circulation found 1) preexisting lung or airway disease; 2) an etiology of arrest drowning or asphyxia; 3) higher pH, and 4) bilateral reactive pupils to be associated with lower mortality. Receiving more than three doses of epinephrine was associated with poor outcome in 96% (44 of 46) of cases. CONCLUSIONS: Multiple factors were identified as associated with survival after out-of-hospital pediatric cardiac arrest with the return of circulation. Additional information available within a few hours after the return of circulation may diminish outcome associations of factors available at earlier times in regression models. These factors should be considered in the design of future interventional trials aimed to improve outcome after pediatric cardiac arrest.

In-hospital versus out-of-hospital pediatric cardiac arrest: a multicenter cohort study.

OBJECTIVES: : To describe a large multicenter cohort of pediatric cardiac arrest (CA) with return of circulation (ROC) from either the in-hospital (IH) or the out-of-hospital (OH) setting and to determine whether significant differences related to pre-event, arrest event, early postarrest event characteristics, and outcomes exist that would be critical in planning a clinical trial of therapeutic hypothermia (TH). DESIGN: : Retrospective cohort study. SETTING: : Fifteen Pediatric Emergency Care Applied Research Network sites. PATIENTS: : Patients aged 24 hours to 18 years with either IH or OH CA who had a history of at least 1 minute of chest compressions and ROC for at least 20 minutes were eligible. INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: : A total of 491 patients met study entry criteria with 353 IH cases and 138 OH cases. Major differences between the IH and OH cohorts were observed for patient prearrest characteristics, arrest event initial rhythm described, and arrest medication use. Several postarrest interventions were used differently, however, the use of TH was similar (<5%) in both cohorts. During the 0-12-hour interval following ROC, OH cases had lower minimum temperature and pH, and higher maximum serum glucose recorded. Mortality was greater in the OH cohort (62% vs. 51%, p = 0.04) with the cause attributed to a neurologic indication much more frequent in the OH than in the IH cohort (69% vs. 20%; p < 0.01). CONCLUSIONS: : For pediatric CA with ROC, several major differences exist between IH and OH cohorts. The finding that the etiology of death was attributed to neurologic indications much more frequently in OH arrests has important implications for future research. Investigators planning to evaluate the efficacy of new interventions, such as TH, should be aware that the IH and OH populations differ greatly and require independent clinical trials.

Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine.

BACKGROUND: The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote "best practices" and to improve patient outcomes. OBJECTIVE: 2007 update of the 2002 American College of Critical Care Medicine Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock. PARTICIPANTS: Society of Critical Care Medicine members with special interest in neonatal and pediatric septic shock were identified from general solicitation at the Society of Critical Care Medicine Educational and Scientific Symposia (2001-2006). METHODS: The Pubmed/MEDLINE literature database (1966-2006) was searched using the keywords and phrases: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation (ECMO), and American College of Critical Care Medicine guidelines. Best practice centers that reported best outcomes were identified and their practices examined as models of care. Using a modified Delphi method, 30 experts graded new literature. Over 30 additional experts then reviewed the updated recommendations. The document was subsequently modified until there was greater than 90% expert consensus. RESULTS: The 2002 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and AHA sanctioned recommendations. Centers that implemented the 2002 guidelines reported best practice outcomes (hospital mortality 1%-3% in previously healthy, and 7%-10% in chronically ill children). Early use of 2002 guidelines was associated with improved outcome in the community hospital emergency department (number needed to treat = 3.3) and tertiary pediatric intensive care setting (number needed to treat = 3.6); every hour that went by without guideline adherence was associated with a 1.4-fold increased mortality risk. The updated 2007 guidelines continue to recognize an increased likelihood that children with septic shock, compared with adults, require 1) proportionally larger quantities of fluid, 2) inotrope and vasodilator therapies, 3) hydrocortisone for absolute adrenal insufficiency, and 4) ECMO for refractory shock. The major new recommendation in the 2007 update is earlier use of inotrope support through peripheral access until central access is attained. CONCLUSION: The 2007 update continues to emphasize early use of age-specific therapies to attain time-sensitive goals, specifically recommending 1) first hour fluid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary refill 70% and cardiac index 3.3-6.0 L/min/m.

Multicenter cohort study of in-hospital pediatric cardiac arrest.

OBJECTIVES: 1) To describe clinical characteristics, hospital courses, and outcomes of a cohort of children cared for within the Pediatric Emergency Care Applied Research Network who experienced in-hospital cardiac arrest with sustained return of circulation between July 1, 2003 and December 31, 2004, and 2) to identify factors associated with hospital mortality in this population. These data are required to prepare a randomized trial of therapeutic hypothermia on neurobehavioral outcomes in children after in-hospital cardiac arrest. DESIGN: Retrospective cohort study. SETTING: Fifteen children's hospitals associated with Pediatric Emergency Care Applied Research Network. PATIENTS: Patients between 1 day and 18 years of age who had cardiopulmonary resuscitation and received chest compressions for >1 min, and had a return of circulation for >20 mins. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 353 patients met entry criteria; 172 (48.7%) survived to hospital discharge. Among survivors, 132 (76.7%) had good neurologic outcome documented by Pediatric Cerebral Performance Category scores. After adjustment for age, gender, and first documented cardiac arrest rhythm, variables available before and during the arrest that were independently associated with increased mortality included pre-existing hematologic, oncologic, or immunologic disorders, genetic or metabolic disorders, presence of an endotracheal tube before the arrest, and use of sodium bicarbonate during the arrest. Variables associated with decreased mortality included postoperative cardiopulmonary resuscitation. Extending the time frame to include variables available before, during, and within 12 hours following arrest, variables independently associated with increased mortality included the use of calcium during the arrest. Variables associated with decreased mortality included higher minimum blood pH and pupillary responsiveness. CONCLUSIONS: Many factors are associated with hospital mortality among children after in-hospital cardiac arrest and return of circulation. Such factors must be considered when designing a trial of therapeutic hypothermia after cardiac arrest in pediatric patients.

Low bias flow oscillation with heliox in oleic acid-induced lung injury.

OBJECTIVE: To evaluate Co(2) clearance in oleic acid-induced lung injury in rabbits receiving high-frequency oscillatory ventilation with helium-oxygen mixtures through a low bias flow oscillation system designed to conserve expensive gases. DESIGN: A prospective, controlled, interventional, in vivo animal laboratory study. SETTING: Research laboratory of a health sciences university. SUBJECTS: Eight New Zealand White Rabbits. INTERVENTIONS: Lung injury (Pao(2)/Fio(2) of <250) was induced by intravenous infusion of oleic acid. Low bias flow oscillation was performed with a modified high-frequency oscillatory ventilation circuit that uses low bias flow (100 mL/kg/min) and a soda lime canister to clear CO(2). Low bias flow oscillation-heliox trials were performed with 40%, 50%, 60%, and 70% helium (balanced with oxygen) for 20 mins. Each heliox trial was preceded by a 20-min paired control trial with 40% oxygen/60% nitrogen. MEASUREMENTS AND MAIN RESULTS: Helium concentrations of 40%, 50%, 60%, and 70% decreased Paco(2) by 13% (47 +/- 7 to 41 +/- 8 torr), 17% (50 +/- 7 to 41 +/- 6 torr), 22% (49 +/- 5 to 38 +/- 7 torr), and 26% (48 +/- 7 to 35 +/- 9 torr), respectively. The gradient between partial pressure of alveolar oxygen and Pao(2) was not affected by 60% helium; however, absolute Pao(2) increased by 15%. Fluid and inotropic requirements were similar in both control and heliox low bias flow oscillation trials. CONCLUSION: Helium concentrations greater than 40% increase Co(2) clearance from oleic acid-injured lungs of rabbits during low bias flow oscillation. The low bias flow oscillation system makes this possible using 1% of the gas volume required during high-frequency oscillatory ventilation.

Perfluorooctyl bromide (perflubron) attenuates oxidative injury to biological and nonbiological systems.

OBJECTIVE: To examine whether perfluorooctyl bromide (perflubron) is capable of protecting biological and nonbiological systems against oxidative damage through a mechanism independent of its known anti-inflammatory property. DESIGN: A controlled, in vitro laboratory study. SETTING: Research laboratory of a health sciences university. SUBJECTS: Rat pulmonary artery endothelial cell cultures (biological system) and linoleic acid in sodium dodecyl sulfate micelles (nonbiological system). INTERVENTIONS: Rat pulmonary artery endothelial cells labeled with dichlorofluorescein diacetate and incubated with perflubron or culture media (control) were exposed to H2O2. H2O2-induced fluorescence of dichlorofluorescein diacetate was measured as an index of intracellular oxidative stress. In another experiment, linoleic acid in sodium dodecyl sulfate micelles was exposed to various concentrations of the azo initiator 2,2'-diazo-bis-(2-amidinopropane) dihydrochloride (2, 4, 20, and 50 mM) in the presence or absence of perflubron. Malondialdehyde measurements were obtained as a marker of oxidative damage to linoleic acid. MEASUREMENTS AND MAIN RESULTS: Cell monolayers incubated with perflubron exhibited 66.6% attenuation in intracellular fluorescence compared with controls (p < .05). Linoleic acid in sodium dodecyl sulfate micelles incubated with perflubron and exposed to 2, 4, 20, or 50 mM of 2,2'-diazo-bis-(2-amidinopropane) dihydrochloride showed less evidence of lipid peroxidation as indicated by lower malondialdehyde measurements at 240 mins (10.6%, 16%, 41%, and 14.2%, respectively) compared with controls. CONCLUSIONS: Perflubron attenuates oxidative damage to both biological and nonbiological systems. This newly recognized property of perflubron is independent of its anti-inflammatory properties.

Heliox enhances carbon dioxide clearance from lungs of normal rabbits during low bias flow oscillation.

OBJECTIVES: To evaluate carbon dioxide clearance in normal rabbits during high-frequency oscillatory ventilation with helium-oxygen mixtures by using a low bias flow oscillation (LBFO) system designed to conserve expensive gas. DESIGN: A prospective, paired-controlled, interventional, in vivo animal laboratory study. SETTING: Animal laboratory of a health science university. SUBJECTS: Twelve New Zealand White rabbits. INTERVENTIONS: Juvenile rabbits were anesthetized, paralyzed, and ventilated through a tracheostomy. LBFO was performed with a modified high-frequency oscillatory ventilation circuit that uses low bias flow (100 mL/kg) and a soda lime cartridge to clear carbon dioxide. LBFO-heliox trials were performed with 20%, 40%, 50%, 60%, and 70% helium (balanced with oxygen) for 30 mins. Each heliox trial was preceded by a paired control trial with 40% oxygen and 60% nitrogen for 30 mins. Ventilator settings in control and heliox trials were identical. During the second part of the study, four rabbits were made hypercapnic by decreasing the power (amplitude), and LBFO was performed with 70% helium against paired-control trials of 40% oxygen and 60% nitrogen. Arterial blood gases were measured at 15-min intervals and airway pressure amplitude was recorded. PaCO2 of control and heliox trials, alveolar PO2-PaO2 gradient of control, and 60% helium trials were compared by paired Student's t-test. MEASUREMENTS AND MAIN RESULTS: At constant power, amplitude was unaffected by helium. Helium concentrations of 40%, 50%, 60%, and 70% decreased PaCO2 by 12%, 33%, 36%, and 46%, respectively. Alveolar PO2-PaO2 gradient was decreased by 40% during ventilation with 60% helium. Under hypercapnic conditions, 70% helium decreased PaCO2 by 20%. CONCLUSION: Helium concentrations > or = 40% facilitate carbon dioxide clearance from lungs of normal rabbits during LBFO. This could be accomplished inexpensively with LBFO due to preservation of heliox when using this device.