Incidence of Air Leak Syndrome in Pediatric Patients With SARS-COV-2 Pneumonia and Respiratory Failure: A Single-Center Retrospective Study.

Air leak syndrome (ALS) is defined as the extrusion of air from an aerated compartment into an unaerated compartment with associated symptoms of respiratory distress. This syndrome can occur as a consequence of trauma, iatrogenic causes, or spontaneously. Retrospective investigations conducted in the adult population have demonstrated an elevated risk of spontaneous ALS development in patients with coronavirus disease 2019 (COVID-19) pneumonia, along with its correlation with mortality. However, no studies have yet explored this phenomenon within the pediatric population. In light of this knowledge gap, we conducted a retrospective chart review comprising 128 pediatric patients ranging in age from one month to 18 years. The primary objective was to assess the incidence of ALS in two distinct groups: patients diagnosed with COVID-19 pneumonia and those with non-COVID-19 viral pneumonia. The groups were compared using Fisher's exact test for sex, the presence of ALS, the requirement of extracorporeal membrane oxygenation (ECMO), and death. The modified Wald method was used to calculate the 95% confidence interval for the mortality rate in patients with COVID-19 pneumonia in the presence of ALS. Our findings revealed a higher prevalence of ALS in patients with COVID-19 pneumonia compared to the non-COVID-19 viral pneumonia group, with a statistically significant P-value of 0.02 and an odds ratio (OR) of 6.72. In terms of mortality rates, there was a statistically significant difference between the two groups (P = 0.025, OR = 1.083). In addition, in patients with ALS in the presence of COVID-19 pneumonia, the mortality rate was 37.5%. However, the requirement of ECMO was not statistically significant (P = 0.16, OR = 1.04). These results suggest that patients with COVID-19 pneumonia have an increased mortality rate and a heightened risk of developing ALS compared to individuals with other viral pneumonias. Furthermore, the presence of ALS was associated with a high mortality rate in COVID-19 pneumonia patients. However, it is crucial to note that obtaining a larger patient sample and involving multiple institutions would be necessary to obtain more consistent and robust data.

Multicentric validation of a prognostic tool for predicting brain death following out-of-hospital cardiac arrest in children.

AIM: Out-of-hospital cardiac arrest (OHCA) in pediatric patients is associated with high rates of mortality and neurologic injury, with no definitive evidence-based method to predict outcomes available. A prognostic scoring tool for adults, The Brain Death After Cardiac Arrest (BDCA) score, was recently developed and validated. We aimed to validate this score in pediatric patients. METHODS: Retrospective cohort study of pediatric patients admitted to 5 PICUs after OHCA between 2011 and 2021. We extracted BDCA score elements for those who survived at least 24 hours but died as a result of their OHCA. We assessed score discrimination for the definitive outcome of brain death. Subgroup analysis was performed for infants < 12mo versus children ≥ 12mo, those who likely had brain death but had withdrawal of life sustaining therapy (WLST) prior to declaration, and by etiology and duration of arrest. RESULTS: 389 subjects were identified across 5 institutions, with 282 meeting inclusion criteria. 169 (59.9%) were formally declared brain dead; 58 (20.6%) had findings consistent with brain death but had withdrawal of life sustaining therapies prior to completion of formal declaration. Area under the receiver operating characteristic curve for the age ≥ 12mo cohort was 0.82 [95% CI 0.75, 0.90], which mirrored the adult subject AUCs of 0.82 [0.77, 0.86] and 0.81 [0.76, 0.86] in the development and validation cohorts. Scores demonstrated worse discrimination in the infant cohort (AUC = 0.61). CONCLUSIONS: The BDCA score shows promise in children ≥ 12mo following OHCA and may be considered in conjunction with existing multimodal prognostication approaches.

Magnesium sulfate infusion for acute asthma in the emergency department.

OBJECTIVES: To describe the role of intravenous magnesium sulfate (MgSO4) as therapy for acute severe asthma in the pediatric emergency department (ED). SOURCE: Publications were searched in the PubMed and Cochrane databases using the following keywords: magnesium AND asthma AND children AND clinical trial. A total of 53 publications were retrieved using this criteria. References of relevant articles were also screened. The authors included the summary of relevant publications where intravenous magnesium sulfate was studied in children (age <18 years) with acute asthma. The NAEPP and Global Initiative for Asthma expert panel guidelines were also reviewed. SUMMARY OF THE DATA: There is a large variability in the ED practices on the intravenous administration of MgSO4 for severe asthma. The pharmacokinetics of MgSO4 is often not taken into account with a consequent impact in its pharmacodynamics properties. The cumulative evidence points to the effectiveness of intravenous MgSO4 in preventing hospitalization, if utilized in a timely manner and at an appropriate dosage (50-75mg/kg). For every five children treated in the ED, one hospital admission could be prevented. Another administration modality is a high-dose continuous magnesium sulfate infusion (HDMI) as 50mg/kg/h/4h (200mg/kg/4h). The early utilization of HDMI for non-infectious mediated asthma may be superior to a MgSO4 bolus in avoiding admissions and expediting discharges from the ED. HDMI appears to be cost-effective if applied early to a selected population. Intravenous MgSO4 has a similar safety profile than other asthma therapies. CONCLUSIONS: Treatment with intravenous MgSO4 reduces the odds of hospital admissions. The use of intravenous MgSO4 in the emergency room was not associated with significant side effects or harm. The authors emphasize the role of MgSO4 as an adjunctive therapy, while corticosteroids and beta agonist remain the primary acute therapeutic agents.

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.

Magnesium sulfate infusion for acute asthma in the emergency department / Infusão de sulfato de magnésio para asma aguda no serviço de emergência

Abstract Objectives: To describe the role of intravenous magnesium sulfate (MgSO4) as therapy for acute severe asthma in the pediatric emergency department (ED). Source: Publications were searched in the PubMed and Cochrane databases using the following keywords: magnesium AND asthma AND children AND clinical trial. A total of 53 publications were retrieved using this criteria. References of relevant articles were also screened. The authors included the summary of relevant publications where intravenous magnesium sulfate was studied in children (age <18 years) with acute asthma. The NAEPP and Global Initiative for Asthma expert panel guidelines were also reviewed. Summary of the data: There is a large variability in the ED practices on the intravenous administration of MgSO4 for severe asthma. The pharmacokinetics of MgSO4 is often not taken into account with a consequent impact in its pharmacodynamics properties. The cumulative evidence points to the effectiveness of intravenous MgSO4 in preventing hospitalization, if utilized in a timely manner and at an appropriate dosage (50-75 mg/kg). For every five children treated in the ED, one hospital admission could be prevented. Another administration modality is a high-dose continuous magnesium sulfate infusion (HDMI) as 50 mg/kg/h/4 h (200 mg/kg/4 h). The early utilization of HDMI for non-infectious mediated asthma may be superior to a MgSO4 bolus in avoiding admissions and expediting discharges from the ED. HDMI appears to be cost-effective if applied early to a selected population. Intravenous MgSO4 has a similar safety profile than other asthma therapies. Conclusions: Treatment with intravenous MgSO4 reduces the odds of hospital admissions. The use of intravenous MgSO4 in the emergency room was not associated with significant side effects or harm. The authors emphasize the role of MgSO4 as an adjunctive therapy, while corticosteroids and beta agonist remain the primary acute therapeutic agents.

Resumo Objetivos: Descrever o papel do sulfato de magnésio intravenoso (MgSO4) como terapia para asma grave aguda em serviço de emergência pediátrica (SE). Fonte: As publicações foram pesquisadas nos bancos de dados PubMed e Cochrane com as seguintes palavras-chave: magnésio E asma E crianças E ensaio clínico. Foram encontradas 53 publicações. As referências de artigos relevantes também foram examinadas. Incluímos o resumo de publicações relevantes quando o sulfato de magnésio intravenoso foi estudado em crianças (idade < 18 anos) com asma aguda. Revisamos também as diretrizes do Programa Nacional para a Educação e Prevenção da Asma (NAEPP) e do painel de especialistas da Iniciativa Global para Asma. Resumo dos dados: Há uma grande variabilidade nas práticas do SE na administração intravenosa do MgSO4 para asma grave. A farmacocinética do MgSO4 normalmente não leva em conta um impacto posterior em suas propriedades farmacodinâmicas. A comprovação cumulativa aponta para a eficácia do MgSO4 intravenoso na prevenção da internação, se usado quando necessário e em uma dosagem adequada (50-75 mg/kg). Uma internação hospitalar pode ser evitada para cada cinco crianças tratadas no SE. Outra modalidade de administração é a infusão prolongada de alta dose de sulfato de magnésio (HDMI) a 50 mg/kg/hora/4 horas (200 mg/kg/4 horas). O uso precoce da HDMI, para asma não infecciosa mediada, pode ser superior a um MgSO4 em bólus para evitar internações e antecipar as altas do SE. A HDMI parece ter bom custo-benefício se aplicada precocemente em uma população selecionada. O MgSO4 intravenoso tem um perfil de segurança semelhante a outras terapias de asma. Conclusões: O tratamento com MgSO4 intravenoso reduz as chances de internações hospitalares. O uso de MgSO4 intravenoso no pronto socorro não é associado a efeitos colaterais ou danos significativos. Enfatizamos o papel do MgSO4 como uma terapia adjuvante, ao passo que os corticosteroides e as beta-agonistas continuam os agentes terapêuticos agudos primários.

Comparison of Two High-Dose Magnesium Infusion Regimens in the Treatment of Status Asthmaticus.

OBJECTIVES: To determine the feasibility and safety of a simplified high-dose magnesium sulfate infusion (sHDMI) for the treatment of status asthmaticus. METHODS: We retrospectively compared 2 different high-dose magnesium sulfate infusion regimens, as adjunctive treatment in status asthmatics, using data that were preciously collected. The initial high-dose, prolonged magnesium infusion (HDMI) regimen consisted of a loading dose of 75 mg/kg (weight ≤ 30 kg) or 50 mg/kg (weight > 30 kg) over a period of 30 to 45 minutes followed by a continuous infusion of 40 mg/kg/hr for an additional 4 hours. This was compared to the sHDMI regimen that consisted of 50 mg/kg/hr for 5 hours. No loading dose was given to the patients in the sHDMI arm. Obese patients were dosed by using ideal body weight. Physiologic parameters (i.e., heart rate, blood pressure, respiratory rate, oxygen saturation) and serum magnesium (SrMg) concentrations were monitored during administration of magnesium sulfate. RESULTS: Nineteen patients receiving the initial HDMI regimen were compared with 10 patients who received the sHDMI regimen. There was no significant difference in SrMg concentrations or physiologic parameters between the 2 dose regimens. CONCLUSIONS: The HDMI and sHDMI regimens both produced SrMg concentrations that are associated with bronchodilation. The safety profile was also similar for the 2 regimens. The unambiguity of sHDMI has the potential to reduce medication errors that are associated with calculation of the loading dose, product preparation, and ultimate administration.

Bedside Optic Nerve Sheath Diameter Assessment in the Identification of Increased Intracranial Pressure in Suspected Idiopathic Intracranial Hypertension.

OBJECTIVE: We determined whether the bedside assessment of the optic nerve sheath diameter could identify elevated intracranial pressure in individuals with suspected idiopathic intracranial hypertension. METHODS: This was a single-center, prospective, rater-blinded study performed in a freestanding pediatric teaching hospital. Patients aged 12 to 18 years scheduled for an elective lumbar puncture with the suspicion of idiopathic intracranial hypertension were eligible to participate. Optic nerve sheath diameter was measured via ultrasonography before performing a sedated lumbar puncture for measuring cerebrospinal fluid opening pressure. Abnormal measurements were predefined as optic nerve sheath diameter ≥4.5 mm and a cerebrospinal fluid opening pressure greater than 20 cmH2O. RESULTS: Thirteen patients participated in the study, 10 of whom had elevated intracranial pressure. Optic nerve sheath diameter was able to predict or rule out elevated intracranial pressure in all patients. CONCLUSIONS: Noninvasive assessment of the optic nerve sheath diameter could help to identify patients with elevated intracranial pressure when idiopathic intracranial hypertension is suspected.

High-Dose Magnesium Sulfate Infusion for Severe Asthma in the Emergency Department: Efficacy Study.

OBJECTIVE: To assess the efficacy of a high-dose prolonged magnesium sulfate infusion in patients with severe, noninfectious-mediated asthma. DESIGN: Prospective, randomized, open-label study. SETTING: Twenty-nine-bed pediatric emergency department located in a children's hospital in Asuncion, Paraguay. PATIENTS: All patients of 6-16 years old who failed to improve after 2 hours of standard therapy for asthma. INTERVENTIONS: Subjects were randomized to receive magnesium sulfate, 50 mg/kg over 1 hour (bolus) or high-dose prolonged magnesium sulfate infusion of 50 mg/kg/hr for 4 hours (max, 8.000 mg/4 hr). Patients were monitored for cardiorespiratory complications. MEASUREMENTS AND MAIN RESULTS: Asthma severity was assessed via asthma scores and peak expiratory flow rates at 0-2-6 hours. The primary outcome was discharge to home at 24 hours. An analysis of the hospital length of stay and costs was a secondary outcome. Thirty-eight patients were enrolled, 19 in each group. The groups were of similar ages, past medical history of asthma, asthma score, and peak expiratory flow rate. There was a significant difference in the patients discharged at 24 hours: 47% in high-dose prolonged magnesium sulfate infusion (9/19) versus 10% (2/21) in the bolus group (p = 0.032) with an absolute risk reduction 37% (95% CI, 10-63) and a number needed to treat of 2.7 (95% CI, 1.6-9.5) to facilitate a discharge at or before 24 hours. The length of stay was shorter in the high-dose prolonged magnesium sulfate infusion group (mean ± SD in hr: high-dose prolonged magnesium sulfate infusion, 34.13 ± 19.54; bolus, 48.05 ± 18.72; p = 0.013; 95% CI, 1.3-26.5). The cost per patient in the high-dose prolonged magnesium sulfate infusion group was one third lower than the bolus group (mean ± SD: high-dose prolonged magnesium sulfate infusion, $603.16 ± 338.47; bolus, $834.37 ± 306.73; p < 0.016). There were no interventions or discontinuations of magnesium sulfate due to adverse events. CONCLUSIONS: The early utilization of high-dose prolonged magnesium sulfate infusion (50 mg/kg/hr/4 hr), for non-infectious mediated asthma, expedites discharges from the emergency department with significant reduction in healthcare cost.

High-dose magnesium sulfate infusion protocol for status asthmaticus: a safety and pharmacokinetics cohort study.

PURPOSE: To assess the safety and pharmacokinetics of high-dose magnesium sulfate (MgSO(4)) infusion in pediatric patients with status asthmaticus. METHODS: A prospective cohort study within a 20-bed pediatric intensive care unit in an academic community hospital. Patients 2-18 years of age admitted with status asthmaticus between 10/2009 and 8/2010 were included in the study. All patients received standard therapy for asthma, while the treatment group received an intravenous magnesium sulfate bolus of 50-75 mg/kg (0.2-0.3 mmol/kg) followed by 40 mg/kg/h (0.16 mmol/kg/h) for 4 h. Patients were monitored for cardiorespiratory complications. The treatment group underwent four blood draws to assess pharmacokinetic parameters. RESULTS: Nineteen patients were in the treatment group and 38 patients in the control group after exclusion criteria and consenting were completed. No clinically significant differences were found between groups. There were no interventions or discontinuations of MgSO(4) due to adverse events. In the treatment group, three patients had mild infusion-related reactions. Heart rate and respiratory rate were statistically significantly lower in the magnesium treatment group. CONCLUSIONS: The continuous infusions of MgSO(4) were safe at the studied doses and maintained serum magnesium (SrMg) and ionized magnesium levels similar to levels required to produce smooth muscle relaxation in other clinical settings. Further studies are needed to investigate the efficacy of high-dose continuous MgSO(4) infusion as an adjunctive treatment for severe asthma treatment and determine the SrMg level required to maintain airway smooth muscle relaxation.

Feasibility of short-term infusion of magnesium sulfate in pediatric patients with status asthmaticus.

OBJECTIVE: This report describes the feasibility of high-dose magnesium sulfate infusion in pediatric patients with status asthmaticus. METHODS: Retrospective chart review over a 3-year period of all patients younger than 18 years of age with status asthmaticus who underwent a high-dose magnesium sulfate infusion for 4 hours. All patients were breathing spontaneously but were refractory to conventional therapy. The magnesium sulfate infusion regimen was 50 mg/kg (for patients weighing >30 kg) or 75 mg/kg (for those weighing ≤30 kg) over a period of 30 to 45 minutes, followed by a continuous infusion of 40 mg/kg/hr for 4 hours. Information regarding vital and clinical respiratory signs, serum magnesium (SrMg), ionized magnesium (iMg), electrocardiograms, and cardiac troponin levels were retrieved. We analyzed the relationship between SrMg and iMg by using linear regression analysis. RESULTS: Nineteen patients were included. At the end of the infusion, SrMg levels were 4.4 ± 0.8 mg/dL, and iMg levels were 0.95 ± 0.2 mmol/L. SrMg levels only moderately predicted iMg (r(2) = 0.541). There were no reports of hypotension, respiratory failure, neurological problems, or nausea. Discomfort at the site of infusion was reported in three cases. Troponin levels (n = 12) and electrocardiograms (n = 12), when available, were noted at the end of the infusion and were normal in all patients p=0.01. CONCLUSIONS: In this case series, short-term high-dose administration of magnesium sulfate in the context of status asthmaticus was feasible, and we did not observe clinical complications with its use. Total SrMg was inadequate to reflect the active form of magnesium, iMg. The dose used achieved theoretical therapeutic levels of iMg.

Primary amebic meningoencephalitis: a case report and literature review.

Primary amebic meningoencephalitis (PAM) is a rare but nearly always fatal disease caused by infection with Naegleria fowleri, a thermophilic, free-living ameba found in freshwater environments. Cases of N. fowleri infection have been reported from many of the southern-tier states in the United States, with Florida and Texas disproportionately represented among them. Primary amebic meningoencephalitis presents clinically in a fashion that may be indistinguishable from bacterial and viral meningitis. Unfortunately, because the disease is so rare, PAM is often excluded from the differential diagnosis of children with meningitis resulting in delayed diagnostic and therapeutic efforts.Pediatric acute care practitioners in emergency departments, general pediatric wards, and critical care units, especially those practicing in the southern United States, should be familiar with the risk factors for acquisition of PAM, its clinical presentation, and the fact that common empiric treatment of bacterial meningitis will not treat N. fowleri. Herein, we present the case of an adolescent who died of PAM and review the (a) epidemiology, (b) pathophysiology, (c) available diagnostic modalities, (d) treatment options, and (e) outcomes of patients treated for N. fowleri infection of the central nervous system.

Postmortem studies in the contemporary pediatric intensive care unit.

OBJECTIVES: To describe the implementation of an educational program that achieved high compliance with autopsy requests and consents in a pediatric intensive care unit. To evaluate the concordance between clinical diagnoses and autopsy findings and to identify patient characteristics in which postmortem diagnosis elucidated the primary disease process. DESIGN: Retrospective, observational study. SETTING: A pediatric intensive care unit in a tertiary care teaching hospital. PATIENTS: All pediatric intensive care unit patients with autopsy reports from 2000 to 2005. INTERVENTIONS: An educational program and protocol were initiated in 1995-1996 to raise awareness and formalize the process for autopsy request. From 2000 to 2005, data were collected from medical records and pathology department autopsy reports. Premortem and postmortem diagnoses were compared utilizing the modified Goldman's classification. The associations of Goldman's classification with age of patients and length of stay were explored. MEASUREMENTS AND MAIN RESULTS: After the educational program was instituted, an autopsy rate of >50% was attained compared to 20%-30% in previous years (p < .05). From 2000 to 2005, 139 autopsies were performed. In 111 patients (79.8%), complete concordance of premortem and postmortem diagnoses was found; in 22 cases (16%), there was no concordance and in six cases the postmortem studies failed to explain the mechanism of death. Autopsies provided new and pertinent findings in 47.5% of all studies, with histologic information accounting for 58% of them. A relationship between short length of stay and the presence of autopsy findings elucidating the main disease process was found (p < .05). CONCLUSIONS: It is feasible to produce a sustainable increase in the rate of postmortem studies within an organization. Autopsy results added new information to almost half of the patients, particularly those who died soon after admission. A pediatric intensive care unit strategy to increase and maintain compliance with autopsy requests is an important practice with favorable clinical and educational repercussions.

Learner's evaluation in paediatric intensive care unit.

OBJECTIVE: To compare post-paediatric intensive care unit (PICU) rotation performance of paediatric residents (PGY-2) and emergency residents (PGY-2) on an online test developed by the subcommittee of the paediatric section of the Society of Critical Care Medicine. Also, to compare residents' performance with that of physician extenders. DESIGN AND SETTINGS: A single centre, longitudinal, retrospective, quality improvement data review in a tertiary care, 20-bed PICU. The test was securely submitted to all residents at the end of their PICU rotation from July 2005 to June 2008. The test was also submitted to physician extenders once only during the 3-year study period. RESULTS: The mean, paediatric residents' (N=30) score was 77.3%±10.8 (SD) and that of emergency residents (N=40) was 82.3%±8.2 (SD) at PGY-2 level (p=0.03). The combined paediatric residents' and emergency residents' mean score was 80.1%±9.7 (SD). The mean physician extenders' (N=7) score was 80.1%±6.5 (SD). CONCLUSION: Emergency residents performed slightly better than paediatric residents on the paediatric-focused knowledge-based online test. The physician extenders' performance was comparable to the individual resident groups' performance and their combined performance.

Hyperacute therapies for childhood stroke: a case report and review of the literature.

Objective. The optimal management of pediatric patients with arterial ischemic stroke (AIS) is not known. Despite this, goal-oriented, time-sensitive therapies geared to rapid reestablishment of arterial blood flow are occasionally applied with beneficial effects. The inconsistent approach to AIS is in part due to a lack of knowledge and preparedness. Methods. Case report of a 12-year-old male with right middle cerebral artery (MCA) occlusion resulting in dense left hemiplegia and mutism and review of the literature. Intervention(s). Mechanical thrombectomy, intra-arterial administration of rt-PA, vasodilators, and platelet inhibitors, and systemic anticoagulation and subsequent critical care support. Results. Restoration of right MCA blood flow and complete resolution of neurologic deficits. Conclusion. We report the gratifying outcome of treatment of a case of AIS in a pediatric patient treated with hyperacute therapies geared to arterial recanalization and subsequent neurologic critical care and review the pertinent literature. Guidelines for the emergency room management of pediatric AIS from prospective, randomized trials are needed.

Fulminant pertussis: a multi-center study with new insights into the clinico-pathological mechanisms.

Pertussis carries a high risk of mortality in very young infants. The mechanism of refractory cardio-respiratory failure is complex and not clearly delineated. We aimed to examine the clinico-pathological features and suggest how they may be related to outcome, by multi-center review of clinical records and post-mortem findings of 10 patients with fulminant pertussis (FP). All cases were less than 8 weeks of age, and required ventilation for worsening respiratory symptoms and inotropic support for severe hemodynamic compromise. All died or underwent extra corporeal membrane oxygenation (ECMO) within 1 week. All had increased leukocyte counts (from 54 to 132 x 10(9)/L) with prominent neutrophilia in 9/10. The post-mortem demonstrated necrotizing bronchitis and bronchiolitis with extensive areas of necrosis of the alveolar epithelium. Hyaline membranes were present in those cases with viral co-infection. Pulmonary blood vessels were filled with leukocytes without well-organized thrombi. Immunodepletion of the thymus, spleen, and lymph nodes was a common feature. Other organisms were isolated as follows; 2/10 cases Para influenza type 3, 2/10 Moraxella catarrhalis, 1/10 each with respiratory syncytial virus (RSV), a coliform organism, methicillin-resistant Staphylococcus aureus (MRSA), Haemophilus influenzae, Stenotrophomonas maltophilia, methicillin-sensitive Staphylococcus aureus (MSSA), and candida tropicalis. We postulate that severe hypoxemia and intractable cardiac failure may be due to the effects of pertussis toxin, necrotizing bronchiolitis, extensive damage to the alveolar epithelium, tenacious airway secretions, and possibly leukostasis with activation of the immunological cascade, all contributing to increased pulmonary vascular resistance. Cellular apoptosis appeared to underlay much of these changes. The secondary immuno-compromise may facilitate co-infection.

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.

Caspases inhibition decreases neurological sequelae in meningitis.

OBJECTIVE: To evaluate the effects of sustained caspase inhibition during the acute phase of meningitis-induced brain injury. Changes in neurobehavioral performance were the primary outcome variables. DESIGN: Randomized prospective animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Animals underwent a basilar cistern inoculation of group B Streptococci to induce meningitis. Sixteen hours later animals were randomized to receive Bocaspartyl (OMe)-fluoromethyketone (BAF) for 4 days or placebo in addition to antibiotic therapy. The assessment of neurobehavioral performance was started 7 days after initiation of treatment and continued for the following 3 wks. A subgroup underwent early kill, at 5 days, to evaluate caspase 3 activity in brain tissue. There was a group of Sham instrumented animals. MEASUREMENTS AND MAIN RESULTS: BAF decreased caspase 3 activation in meningitic animals. There were no significant motor deficit differences between the infected groups. Cognitive performance was significantly improved in the BAF group. CONCLUSION: These findings demonstrate that sustained systemic administration of BAF inhibits caspase 3 activation and decreases neurologic sequelae in a rat model of bacterial meningitis.

Pharmacologic support of infants and children in septic shock.

OBJECTIVES: Septic shock (SS) is a frequent cause for admission to the pediatric intensive care unit, requiring prompt recognition and intervention to improve outcome. Our aim is to review the relevant literature related to the diagnosis and management of SS and present a sequential management for its treatment. SOURCES: Non-systematic review of medical literature using the MEDLINE database. Articles were selected according to their relevance to the objective and according to the authors' opinions. SUMMARY OF THE FINDINGS: The outcome of sepsis and SS is dependent on the early recognition and implementation of time-sensitive goal-directed therapies. These include rapid aggressive fluid resuscitation followed by a well-designed pharmacotherapy. The goals of the resuscitation are the restoration of microcirculation and improved organ tissue perfusion. Clinical and laboratory markers are needed to assess the adequacy of the treatments. Altered pharmacokinetic and pharmacodynamic responses dictate that vasoactive agents should be adjusted to achieve the predetermined goals. In initial resuscitation with isotonic solutions (> 60 mL/kg), either crystalloid (normal saline) or colloid infusion could be used. Despite adequate fluid resuscitation, if: (a) wide pulse pressure, low blood pressure, or bounding pulses (high cardiac output, low systemic vascular resistance--SVR) are present, norepinephrine should be considered; (b) prolonged capillary refill, weak pulses, narrow pulse pressure, normotensive (low cardiac output, high SVR), dopamine, epinephrine or dobutamine should be considered. Adjunctive therapy with stress dose of corticosteroid is indicated in selected populations. CONCLUSIONS: Septic shock hemodynamics is a changing process that requires frequent assessment and therapeutic adjustments.