Pediatric Critical Care Medicine

Identification of Pediatric Sepsis for Epidemiologic Surveillance Using Electronic Clinical Data* Objectives: A method to identify pediatric sepsis episodes that is not affected by changing diagnosis and claims-based coding practices does not exist. We derived and validated a surveillance algorithm to identify pediatric sepsis using routine clinical data and applied the algorithm to study longitudinal trends in sepsis epidemiology. Design: Retrospective observational study. Setting: Single academic children’s hospital. Patients: All emergency and hospital encounters from January 2011 to January 2019, excluding neonatal ICU and cardiac center. Exposure: Sepsis episodes identified by a surveillance algorithm using clinical data to identify infection and concurrent organ dysfunction. Interventions None. Measurements and Main Results: A surveillance algorithm was derived and validated in separate cohorts with suspected sepsis after clinician-adjudication of final sepsis diagnosis. We then applied the surveillance algorithm to determine longitudinal trends in incidence and mortality of pediatric sepsis over 8 years. Among 93,987 hospital encounters and 1,065 episodes of suspected sepsis in the derivation period, the surveillance algorithm yielded sensitivity 78% (95% CI, 72–84%), specificity 76% (95% CI, 74–79%), positive predictive value 41% (95% CI, 36–46%), and negative predictive value 94% (95% CI, 92–96%). In the validation period, the surveillance algorithm yielded sensitivity 84% (95% CI, 77–92%), specificity of 65% (95% CI, 59–70%), positive predictive value 43% (95% CI, 35–50%), and negative predictive value 93% (95% CI, 90–97%). Notably, most “false-positives” were deemed clinically relevant sepsis cases after manual review. The hospital-wide incidence of sepsis was 0.69% (95% CI, 0.67–0.71%), and the inpatient incidence was 2.8% (95% CI, 2.7–2.9%). Risk-adjusted sepsis incidence, without bias from changing diagnosis or coding practices, increased over time (adjusted incidence rate ratio per year 1.07; 95% CI, 1.06–1.08; p < 0.001). Mortality was 6.7% and did not change over time (adjusted odds ratio per year 0.98; 95% CI, 0.93–1.03; p = 0.38). Conclusions: An algorithm using routine clinical data provided an objective, efficient, and reliable method for pediatric sepsis surveillance. An increased sepsis incidence and stable mortality, free from influence of changes in diagnosis or billing practices, were evident.

Clinical Characteristics, Major Morbidity, and Mortality in Trauma-Related Pediatric Acute Respiratory Distress Syndrome* Objectives: To determine the presence, central characteristics, and impact on major morbidity and mortality of trauma-related pediatric acute respiratory distress syndrome. Design: Retrospective review of a prospective trauma database. Setting: American College of Surgeons verified level 1 trauma center in an urban setting. Patients: Trauma patients age 0 to 18 years old inclusive. Interventions: None. Measurements and Main Results: Of the 7,382 patients presenting within the 10-year study period, 646 met study criteria for inclusion in the analysis. Trauma-related pediatric acute respiratory distress syndrome was present in 9% of the analyzed cohort. On univariate analysis and compared with those without, trauma-related pediatric acute respiratory distress syndrome occurred more commonly among those with traumatic brain injury (77.2% vs 45.5%; p < 0.001), non-accidental trauma (28.8% vs 10.2%; p < 0.001), and an injury severity score greater than 30 (27.1% vs 3.8%; p 0.001). New or progressive multiple organ dysfunction syndrome was significantly higher in trauma-related pediatric acute respiratory distress syndrome patients (86.7% vs 10.4%; p < 0.001) as was mortality (18.3% vs 3.1%; p < 0.001) than in those without. The presence of trauma-related pediatric acute respiratory distress syndrome (odds ratio, 6.98; 95% CI, 2.95–16.5; p < 0.001), younger age (odds ratio, 0.93; 95% CI, 0.87–0.99; p = 0.038), and worse injury severity (odds ratio, 1.19; 95% CI, 1.14–1.24; p < 0.001) were all independent statistical predictors of new or progressive multiple organ dysfunction syndrome in this retrospective cohort. Mortality in patients without trauma-related pediatric acute respiratory distress syndrome increased with increasing injury severity, whereas mortality in patients with trauma-related pediatric acute respiratory distress syndrome was the same regardless of injury severity. On multivariable regression analysis, while age and injury severity were independent statistical predictors of mortality, trauma-related pediatric acute respiratory distress syndrome was not (odds ratio, 2.35; 95% CI, 0.88–6.28; p = 0.087). Conclusions: Pediatric acute respiratory distress syndrome is present in the pediatric trauma population. Trauma-related pediatric acute respiratory distress syndrome is associated with eight times the organ dysfunction and five times the mortality compared with patients without trauma-related pediatric acute respiratory distress syndrome, yet research in this area is lacking. Further prospective, mechanistic evaluations are essential to understand why these patients are at risk and how to effectively intervene to improve outcomes.

Performance of a Clinical Decision Support Tool to Identify PICU Patients at High Risk for Clinical Deterioration* Objectives: To evaluate the translation of a paper high-risk checklist for PICU patients at risk of clinical deterioration to an automated clinical decision support tool. Design: Retrospective, observational cohort study of an automated clinical decision support tool, the PICU Warning Tool, adapted from a paper checklist to predict clinical deterioration events in PICU patients within 24 hours. Setting: Two quaternary care medical-surgical PICUs—The Children’s Hospital of Philadelphia and Cincinnati Children’s Hospital Medical Center. Patients: The study included all patients admitted from July 1, 2014, to June 30, 2015, the year prior to the initiation of any focused situational awareness work at either institution. Interventions: We replicated the predictions of the real-time PICU Warning Tool by retrospectively querying the institutional data warehouse to identify all patients that would have flagged as high-risk by the PICU Warning Tool for their index deterioration. Measurements and Main Results: The primary exposure of interest was determination of high-risk status during PICU admission via the PICU Warning Tool. The primary outcome of interest was clinical deterioration event within 24 hours of a positive screen. The date and time of the deterioration event was used as the index time point. We evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of the performance of the PICU Warning Tool. There were 6,233 patients evaluated with 233 clinical deterioration events experienced by 154 individual patients. The positive predictive value of the PICU Warning Tool was 7.1% with a number needed to screen of 14 patients for each index clinical deterioration event. The most predictive of the individual criteria were elevated lactic acidosis, high mean airway pressure, and profound acidosis. Conclusions: Performance of a clinical decision support translation of a paper-based tool showed inferior test characteristics. Improved feasibility of identification of high-risk patients using automated tools must be balanced with performance.

Parental Conflict, Regret, and Short-term Impact on Quality of Life in Tracheostomy Decision-Making Objectives: The prevalence of tracheostomy-dependence in critically ill children is increasing in the United States. We do not know the impact of this decision on parental outcomes. We aimed to determine the prevalence of decisional conflict and regret and explore the impact on quality of life among parents considering tracheostomy placement for their child. Subjects: Parents facing tracheostomy decision for their child. Design: Prospective, mixed-methods longitudinal study. Setting: PICU, cardiac ICU, and neonatal ICU of a single quaternary medical center. Interventions: None. Measurements and Main Results: Parents completed a decisional conflict survey at the time of tracheostomy decision and decisional regret and quality of life surveys at 2 weeks and 3 months after the decision regarding tracheostomy placement was made. We enrolled 39 parents, of which 25 completed surveys at all three time points. Thirty-five of 39 (89.7%) reported at least some decisional conflict, most commonly from feeling uninformed and pressured to make a decision. At 2 weeks, 13 of 25 parents (52%) reported regret, which increased to 18 of 25 participants (72%) at 3 months. Regret stemmed from feeling uninformed, ill-chosen timing of placement, and perceptions of inadequate medical care. At 2 weeks, the quality of life score was in the mid-range, 78.8 (sd 13.8) and decreased to 75.5 (sd 14.2) at 3 months. Quality of life was impacted by the overwhelming medical care and complexity of caring for a child with a tracheostomy, financial burden, and effect on parent’s psychosocial health. Conclusions: The decision to pursue tracheostomy among parents of critically ill children is fraught with conflict with worsening regret and quality of life over time. Strategies to reduce contributing factors may improve parental outcomes after this life-changing decision.

Association of Duration of Hypotension With Survival After Pediatric Cardiac Arrest Objectives: To evaluate the association of a single episode of hypotension and burden of hypotension with survival to hospital discharge following resuscitation from pediatric cardiac arrest. Design: Retrospective cohort study. Setting: Single-center PICU. Patients: Patients between 1 day and 18 years old who had a cardiac arrest, received chest compressions for more than 2 minutes, had return of spontaneous circulation for more than 20 minutes, and survived to receive postresuscitation care in the ICU. Interventions: None. Measurement and Main Results: One-hundred sixteen patients were evaluable. Hypotension, defined as systolic blood pressure less than the fifth percentile for age and sex, occurred in 37 patients (32%) within the first 6 hours and 64 (55%) within 72 hours of postresuscitation ICU care. There was no significant difference in survival to discharge for patients who had a single episode of hypotension within 6 hours (51% vs 69%; p = 0.06) or within 72 hours (56% vs 73%; p = 0.06). Burden of hypotension was defined as the percentage of hypotension measurements that were below the fifth percentile. After controlling for patient and cardiac arrest event characteristics, a higher burden of hypotension within the first 72 hours of ICU postresuscitation care was associated with decreased discharge survival (adjusted odds ratio = 0.67 per 10% increase in hypotension burden; 95% CI, 0.48–0.86; p = 0.006). Conclusions: After successful resuscitation from pediatric cardiac arrest, systolic hypotension was common (55%). A higher burden of postresuscitation hypotension within the first 72 hours of ICU postresuscitation care was associated with significantly decreased discharge survival, after accounting for potential confounders including number of doses of epinephrine, arrest location, and arrest etiology due to airway obstruction or trauma.

Vacuum-Assisted Closure for the Treatment of Deep Sternal Wound Infection After Pediatric Cardiac Surgery Objectives: Vacuum-assisted closure is being increasingly used to treat deep sternal wound infection following cardiac surgery, but most of the data refer to adults. This study investigated the safety and efficacy of vacuum-assisted closure in pediatric patients. Design: Retrospective file review. Setting: Tertiary pediatric medical center. Patients: All children with deep sternal wound infection treated with vacuum-assisted closure in 2003–2016. Interventions: Epidemiological, clinical, and microbiological data were collected from the medical records. Measurements and Main Results: The cohort included 50 patients (0.9% of cardiac patients operated during the study period) of median age 6.5 months (interquartile range, 2–12.75 mo; range, 1 wk to 14 yr) and median weight 5.1 kg (interquartile range, 4–9.75 kg). The most frequent heart defects were tetralogy of Fallot (22%) and ventricular septal defect (20%); 38% of patients had cyanotic heart disease. Deep sternal wound infections appeared a median of 10 days postoperatively (interquartile range, 7–14 d; range 3–100 d). Vacuum-assisted closure was applied a median of 13 days postoperatively (interquartile range, 10–18.5 d; range, 5–103 d) for a median duration of 10 days (interquartile range, 7–13.25 d; range, 1–21 d). Wound cultures were positive in 48 patients (96%); most isolates were Gram-positive (76%). The main bacterial pathogen was methicillin-susceptible Staphylococcus aureus (61%). Most patients were treated with cloxacillin for a median of 38 days (interquartile range, 28–42 d; range, 9–189 d). There were no statistically significant differences in clinical or treatment characteristics between bacteremic (56%) and nonbacteremic patients. Compared with older patients, infants less than 3 months old (36%) had a significantly longer hospitalization time (41 vs 25 d; p = 0.001) and higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category (3 vs 2; p = 0.003). All cases except one (contact dermatitis) were uneventful. In 10 patients, wounds were closed surgically after vacuum-assisted closure. Two patients required a pectoralis flap, both treated before 2005. One of the two deaths was infection-related. Conclusions: Vacuum-assisted closure is a feasible treatment option of deep sternal wound infection after pediatric cardiac surgery and was not associated with independent morbidity.

Clinical Effects and Outcomes After Polymyxin B–Immobilized Fiber Column Direct Hemoperfusion Treatment for Septic Shock in Preterm Neonates* Objectives: To compare the effectiveness and mortality of early-onset sepsis or late-onset sepsis treatments with polymyxin B–immobilized fiber column direct hemoperfusion in terms of effectiveness and mortality in preterm infants with septic shock. Design: Retrospective cohort study. Setting: Neonatal ICU within a tertiary care hospital. Patients: Of 1,115 patients, 49 had blood culture–proven sepsis between January 2013 and December 2018; six and five patients with septic shock had undergone polymyxin B–immobilized fiber column direct hemoperfusion treatment for early-onset sepsis (early-onset sepsis group) and late-onset sepsis (late-onset sepsis group), respectively. Interventions: None. Measurements and Main Results: Baseline demographic characteristics of both groups were similar. The time from decision to treatment induction was significantly shorter in the early-onset sepsis group than that in the late-onset sepsis group (p = 0.008). The mortality rate after 28 days of treatment and the hospital mortality were significantly lower in the early-onset sepsis group than in the late-onset sepsis group (p = 0.026 and 0.015, respectively). The Pao2/Fio2 ratio was significantly higher in the early-onset sepsis group than in the late-onset sepsis group at the end of the treatment (p = 0.035). In addition, median arterial-to-alveolar oxygen tension ratio significantly improved from 0.19 to 0.55, and median blood pressure also significantly improved from 32.5 to 40.0 mm Hg after the treatment in the early-onset sepsis group. Interleukin-6 levels significantly decreased after treatment in the early-onset sepsis group (p = 0.037). The Pediatric Risk of Mortality III score was similar between the early-onset sepsis and late-onset sepsis groups before and after the treatment. Intraventricular hemorrhage events occurred in both groups, but with no significant differences (p = 0.175). Conclusions: Polymyxin B–immobilized fiber column direct hemoperfusion treatment for preterm infants with septic shock due to early-onset sepsis is associated with earlier hemodynamic and respiratory status improvements and with lower mortality than that due to late-onset sepsis. Early neonatal septic shock detection and polymyxin B–immobilized fiber column direct hemoperfusion induction may improve the prognosis of affected infants.

Fluid Overload in Pediatric Severe Traumatic Brain Injury* Objective: Pediatric traumatic brain injury is a major public health problem in the United States. Hypertonic saline therapy is a well-established treatment in patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) who have intracranial hypertension. In children, fluid overload is associated with increased mortality, ventilator duration, and length of PICU stay, even when controlling for severity of illness. This study reports prevalence of fluid overload in pediatric patients with severe traumatic brain injury treated with 3% hypertonic saline and effect on clinical outcomes. Design: Single-center retrospective chart review. Setting: PICUs at two tertiary children’s hospitals. Patients: One hundred thirty-eight patients with traumatic brain injury with postresuscitation Glasgow Coma Scale less than or equal to 8 who received hypertonic saline from September 1, 2010, to February 28, 2016, and intracranial pressure monitoring and survived at least 24 hours from admission. Interventions: None. Measurements and Main Results: We used fluid balance percentage greater than or equal to 10% as our definition of fluid overload. Ninety-one percent of patients less than 1 year old had fluid overload on day 10 of admission compared with 47% of patients greater than 1 year. Fluid overloaded patients did not have increased mortality, acute kidney injury, PICU length of stay, or ventilator days. Hypertonic saline was not the cause of fluid overload in these patients. Conclusions: Patients with severe traumatic brain injury do have high rates of fluid overload. However, fluid overload did not contribute to mortality, longer days on the ventilator, increased risk of acute kidney injury, or increased PICU length of stay.

Assessment of the Independent and Synergistic Effects of Fluid Overload and Acute Kidney Injury on Outcomes of Critically Ill Children* Objectives: Evaluate the independent and synergistic associations of fluid overload and acute kidney injury with outcome in critically ill pediatric patients. Design: Secondary analysis of the Acute Kidney Injury in Children Expected by Renal Angina and Urinary Biomarkers (NCT01735162) prospective observational study. Setting: Single-center quaternary level PICU. Patients: One-hundred forty-nine children 3 months to 25 years old with predicted PICU length of stay greater than 48 hours, and an indwelling urinary catheter enrolled (September 2012 to March 2014). Acute kidney injury (defined by creatinine or urine output on day 3) and fluid overload (≥ 20% on day 3) were used as outcome variables and risk factors for ICU endpoints assessed at 28 days. Interventions: None. Measurements and Main Results: Acute kidney injury and fluid overload occurred in 19.4% and 24.2% respectively. Both acute kidney injury and fluid overload were associated with longer ICU length of stay but neither maintained significance after multivariate regression. Delineation into unique fluid overload/acute kidney injury classifications demonstrated that fluid overload+ patients experienced a longer ICU and hospital length of stay and higher rate of mortality compared with fluid overload– patients, regardless of acute kidney injury status. Fluid overload+/acute kidney injury– patients had increased odds of death (p = 0.013). After correction for severity of illness, ICU length of stay remained significantly longer in fluid overload+/acute kidney injury+ patients compared with patients without both classifications (17.4; 95% CI, 11.0–23.7 vs 8.8; 95% CI, 7.3–10.9; p = 0.05). Correction of acute kidney injury classification for net fluid balance led to acute kidney injury class switching in 29 patients and strengthened the association with increased mechanical ventilation and ICU length of stay on bivariate analysis, but reduced the increased risk conferred by fluid overload for mortality. Conclusions: The current study suggests the effects of significant fluid accumulation may be delineable from the effects of acute kidney injury. Concurrent fluid overload and acute kidney injury significantly worsen outcome. Correction of acute kidney injury assessment for net fluid balance may refine diagnosis and unmask acute kidney injury associated with deleterious downstream sequelae. The unique effects of fluid overload and acute kidney injury on outcome in critically ill patients warrant further study.

Platelet Transfusion Practice and Related Outcomes in Pediatric Extracorporeal Membrane Oxygenation* Objective: To describe factors associated with platelet transfusion during pediatric extracorporeal membrane oxygenation and the relationships among platelet transfusion, complications, and mortality. Design: Secondary analysis of data collected prospectively by the Collaborative Pediatric Critical Care Research Network between December 2012 and September 2014. Setting: Eight Collaborative Pediatric Critical Care Research Network–affiliated hospitals. Patients: Age less than 19 years old and treated with extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Of 511 children, 496 (97.1%) received at least one platelet transfusion during extracorporeal membrane oxygenation. Neonatal age, venoarterial extracorporeal membrane oxygenation, and various acute and chronic diagnoses were associated with increased average daily platelet transfusion volume (milliliters per kilogram body weight). On multivariable analysis, average daily platelet transfusion volume was independently associated with mortality (per 1 mL/kg; odds ratio, 1.05; CI, 1.03–1.08; p < 0.001), whereas average daily platelet count was not (per 1 × 109/L up to 115 × 109/L; odds ratio, 1.00; CI, 0.98–1.01; p = 0.49). Variables independently associated with increased daily bleeding risk included increased platelet transfusion volume on the previous extracorporeal membrane oxygenation day, a primary cardiac indication for extracorporeal membrane oxygenation, adolescent age, and an acute diagnosis of congenital cardiovascular disease. Variables independently associated with increased daily thrombotic risk included increased platelet transfusion volume on the previous extracorporeal membrane oxygenation day and venoarterial extracorporeal membrane oxygenation. Variables independently associated with decreased daily thrombotic risk included full-term neonatal age and an acute diagnosis of airway abnormality. Conclusions: Platelet transfusion was common in this multisite pediatric extracorporeal membrane oxygenation cohort. Platelet transfusion volume was associated with increased risk of mortality, bleeding, and thrombosis.