Exposure to Sedation and Analgesia Medications: Short-term Cognitive Outcomes in Pediatric Critical Care Survivors With Acquired Brain Injury.

Background/Objective: Pediatric intensive care unit (PICU) survivors risk significant cognitive morbidity, particularly those with acquired brain injury (ABI) diagnoses. Studies show sedative and analgesic medication may potentiate neurologic injury, but few studies evaluate impact on survivor outcomes. This study aimed to evaluate whether exposures to analgesic and sedative medications are associated with worse neurocognitive outcome. Methods: A retrospective cohort study was conducted of 91 patients aged 8 to 18 years, undergoing clinical neurocognitive evaluation approximately 1 to 3 months after PICU discharge. Electronic health data was queried for sedative and analgesic medication exposures, including opioids, benzodiazepines, propofol, ketamine, and dexmedetomidine. Doses were converted to class equivalents, evaluated by any exposure and cumulative dose exposure per patient weight. Cognitive outcome was derived from 8 objective cognitive assessments with an emphasis on executive function skills using Principal Components Analysis. Then, linear regression was used to control for baseline cognitive function estimates to calculate a standardized residualized neurocognitive index (rNCI) z-score. Multivariable linear regression evaluated the association between rNCI and medication exposure controlling for covariates. Significance was defined as P < .05. Results: Most (n = 80; 88%) patients received 1 or more study medications. Any exposure and higher cumulative doses of benzodiazepine and ketamine were significantly associated with worse rNCI in bivariate analyses. When controlling for Medicaid, preadmission comorbid conditions, length of stay, delirium, and receipt of other medication classes, receipt of benzodiazepine was associated with significantly worse rNCI (ß-coefficient = -0.48, 95% confidence interval = -0.88, -0.08). Conclusions: Exposure to benzodiazepines was independently associated with worse acute phase cognitive outcome using objective assessments focused on executive function skills when controlling for demographic and illness characteristics. Clinician decisions regarding medication regimens in the PICU may serve as a modifiable factor to improve outcomes. Additional inquiry into associations with long-term cognitive outcome and optimal medication regimens is needed.

Effect of apneic oxygenation with intubation to reduce severe desaturation and adverse tracheal intubation-associated events in critically ill children.

BACKGROUND: Determine if apneic oxygenation (AO) delivered via nasal cannula during the apneic phase of tracheal intubation (TI), reduces adverse TI-associated events (TIAEs) in children. METHODS: AO was implemented across 14 pediatric intensive care units as a quality improvement intervention during 2016-2020. Implementation consisted of an intubation safety checklist, leadership endorsement, local champion, and data feedback to frontline clinicians. Standardized oxygen flow via nasal cannula for AO was as follows: 5 L/min for infants (< 1 year), 10 L/min for young children (1-7 years), and 15 L/min for older children (≥ 8 years). Outcomes were the occurrence of adverse TIAEs (primary) and hypoxemia (SpO2 < 80%, secondary). RESULTS: Of 6549 TIs during the study period, 2554 (39.0%) occurred during the pre-implementation phase and 3995 (61.0%) during post-implementation phase. AO utilization increased from 23 to 68%, p < 0.001. AO was utilized less often when intubating infants, those with a primary cardiac diagnosis or difficult airway features, and patient intubated due to respiratory or neurological failure or shock. Conversely, AO was used more often in TIs done for procedures and those assisted by video laryngoscopy. AO utilization was associated with a lower incidence of adverse TIAEs (AO 10.5% vs. without AO 13.5%, p < 0.001), aOR 0.75 (95% CI 0.58-0.98, p = 0.03) after adjusting for site clustering (primary analysis). However, after further adjusting for patient and provider characteristics (secondary analysis), AO utilization was not independently associated with the occurrence of adverse TIAEs: aOR 0.90, 95% CI 0.72-1.12, p = 0.33 and the occurrence of hypoxemia was not different: AO 14.2% versus without AO 15.2%, p = 0.43. CONCLUSION: While AO use was associated with a lower occurrence of adverse TIAEs in children who required TI in the pediatric ICU after accounting for site-level clustering, this result may be explained by differences in patient, provider, and practice factors. Trial Registration Trial not registered.

Recognizing Pediatric ARDS: Provider Use of the PALICC Recommendations in a Tertiary Pediatric ICU.

BACKGROUND: For almost 50 years, pediatricians used adult guidelines to diagnose ARDS. In 2015, specific criteria for pediatric ARDS were defined. However, it remains unclear how frequently providers recognize pediatric ARDS and whether recognition affects adherence to consensus recommendations. METHODS: This was a mixed-method, retrospective study of mechanically ventilated pediatric subjects after the release of the pediatric ARDS recommendation statement. Pediatric ARDS cases were identified according to the new criteria. Provider recognition was defined by documentation in the medical record. Pediatric ARDS subjects with and without provider recognition were compared quantitatively according to clinical characteristics, adherence to lung-protective ventilation (LPV), adjunctive therapies, and outcomes. A qualitative document analysis (QDA) was performed to evaluate knowledge and beliefs surrounding the Pediatric Acute Lung Injury Consensus Conference recommendations. RESULTS: Of 1,983 subject encounters, pediatric ARDS was identified in 321 (16%). Provider recognition was present in 97 (30%) cases and occurred more often in subjects who were older, had worse oxygenation deficits, or were bone marrow transplant recipients. Recognition rates increased each studied year. LPV practices did not differ based on provider recognition; however, subjects who received it were more likely to experience permissive hypoxemia and adherence to extrapulmonary recommendations. Ultimately, there was no differences in outcomes between the provider recognition and non-provider recognition groups. Three themes emerged from the QDA: (1) pediatric ARDS presents within a complex, multidimensional context, with potentially competing organ system failures; (2) similar to historical conceptualizations, pediatric ARDS was often considered a visual diagnosis, with measures of oxygenation unreferenced; and (3) emphasis was placed on non-evidence-based interventions, such as pulmonary clearance techniques, rather than on consensus recommendations. CONCLUSIONS: Among mechanically ventilated children, pediatric ARDS was common but recognized in a minority of cases. Potential opportunities, such as an opt-out approach to LPV, may exist for improved dissemination and implementation of recommended best practices.

Association of Diagnostic Stewardship for Blood Cultures in Critically Ill Children With Culture Rates, Antibiotic Use, and Patient Outcomes: Results of the Bright STAR Collaborative.

Importance: Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics. Objective: To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes. Design, Setting, and Participants: This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes. Exposures: A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative). Main Outcomes and Measures: The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock. Results: Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation. Conclusions and Relevance: Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

Ketamine Use for Tracheal Intubation in Critically Ill Children Is Associated With a Lower Occurrence of Adverse Hemodynamic Events.

OBJECTIVES: Tracheal intubation in critically ill children with shock poses a risk of hemodynamic compromise. Ketamine has been considered the drug of choice for induction in these patients, but limited data exist. We investigated whether the administration of ketamine for tracheal intubation in critically ill children with or without shock was associated with fewer adverse hemodynamic events compared with other induction agents. We also investigated if there was a dose dependence for any association between ketamine use and adverse hemodynamic events. DESIGN: We performed a retrospective analysis using prospectively collected observational data from the National Emergency Airway Registry for Children database from 2013 to 2017. SETTING: Forty international PICUs participating in the National Emergency Airway Registry for Children. PATIENTS: Critically ill children 0-17 years old who underwent tracheal intubation in a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The association between ketamine exposure as an induction agent and the occurrence of adverse hemodynamic events during tracheal intubation including dysrhythmia, hypotension, and cardiac arrest was evaluated. We used multivariable logistic regression to account for patient, provider, and practice factors with robust SEs to account for clustering by sites. Of 10,750 tracheal intubations, 32.0% (n = 3,436) included ketamine as an induction agent. The most common diagnoses associated with ketamine use were sepsis and/or shock (49.7%). After adjusting for potential confounders and sites, ketamine use was associated with fewer hemodynamic tracheal intubation associated adverse events compared with other agents (adjusted odds ratio, 0.74; 95% CI, 0.58-0.95). The interaction term between ketamine use and indication for shock was not significant (p = 0.11), indicating ketamine effect to prevent hemodynamic adverse events is consistent in children with or without shock. CONCLUSIONS: Ketamine use for tracheal intubation is associated with fewer hemodynamic tracheal intubation-associated adverse events.

Hospital Mortality and Functional Outcomes in Pediatric Neurocritical Care.

OBJECTIVES: Pediatric neurocritical care (PNCC) outcomes research is scarce. We aimed to expand knowledge about outcomes in PNCC by evaluating death and changes in Functional Status Scale (FSS) from baseline among PNCC diagnoses. METHODS: We conducted a 2-year observational study of children aged 0 to 18 years admitted to the ICU with a primary neurologic diagnosis (N = 325). Primary outcomes were death and change in FSS from preadmission baseline to discharge. New disability was defined as an FSS change of ≥1 from baseline, and severe disability was defined as an FSS change of ≥3. Categorical results are reported as relative risk (RR) with 95% confidence interval (CI). RESULTS: Thirty (9%) patients died. New disability (n = 103; 35%) and severe disability (n = 37; 13%) were common in PNCC survivors. New disability (range 14%-54%) and severe disability (range 3%-33%) outcomes varied significantly among primary diagnoses (lowest in status epilepticus; highest in infectious and/or inflammatory and stroke cohorts). Disability occurred in all FSS domains: mental status (15%), sensory (52%), communication (38%), motor (48%), feeding (40%), and respiratory (12%). Most (64%) patients with severe disability had changes in ≥3 domains. Requiring critical care interventions (RR 2.1; 95% CI 1.5-3.1) and having seizures (RR 1.5; 95% CI 1.1-2.0) during hospitalization were associated with new disability. CONCLUSIONS: PNCC patients have high rates of death and new disability at discharge, varying significantly between PNCC diagnoses. Multiple domains of disability are affected, underscoring the ongoing multidisciplinary health care needs of survivors. Our study quantified hospital outcomes of PNCC patients that can be used to advance future research in this vulnerable population.

Pediatric Ventilator-Associated Events: Analysis of the Pediatric Ventilator-Associated Infection Data.

OBJECTIVES: To compare the prevalence of infection applying the proposed pediatric ventilator-associated events criteria versus clinician-diagnosed ventilator-associated infection to subjects in the pediatric ventilator-associated infection study. DESIGN: Analysis of prospectively collected data from the pediatric ventilator-associated infection study. SETTING: PICUs of 47 hospitals in the United States, Canada, and Australia. PATIENTS: Two-hundred twenty-nine children ventilated for greater than 48 hours who had respiratory secretion cultures performed to evaluate for suspected ventilator-associated infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Applying the proposed pediatric ventilator-associated event criteria, 15 of 229 subjects in the ventilator-associated infection study qualified as "ventilator-associated condition" and five of 229 (2%) met criteria for "infection-related ventilator-associated complication." This was compared with 89 of 229 (39%) diagnosed as clinical ventilator-associated infection (Kappa = 0.068). Ten of 15 subjects identified as ventilator-associated condition did not meet criteria for infection-related ventilator-associated complication primarily because they did not receive 4 days of antibiotics. Ventilator-associated condition subjects were similar demographically to nonventilator-associated condition subjects and had similar mortality (13% vs 10%), PICU-free days (6.9 ± 7.7; interquartile range, 0-14 vs 9.8 ± 9.6; interquartile range, 0-19; p = 0.25), but fewer ventilator-free days (6.6 ± 9.3; interquartile range, 1-15 vs 12.4 ± 10.7; interquartile range, 0-22; p = 0.04). The clinical ventilator-associated infection diagnosis in the ventilator-associated infection study was associated with fewer PICU-free days but no difference in mortality or ventilator-free days. CONCLUSIONS: The ventilator-associated event criteria appear to be insensitive to the clinical diagnosis of ventilator-associated infection. Differentiation between ventilator-associated condition and infection-related ventilator-associated complication was primarily determined by the clinician decision to treat with antibiotics rather than clinical signs and symptoms. The utility of the proposed pediatric ventilator-associated event criteria as a surrogate for ventilator-associated infection criteria is unclear.

Long-term Sequelae of Pediatric Neurocritical Care: The Parent Perspective.

Critical neurologic disease and injury affect thousands of children annually with survivors suffering high rates of chronic morbidities related directly to the illness and to critical care hospitalization. Postintensive care syndrome (PICS) in patients and families encompasses a variety of morbidities including physical, cognitive, emotional, and psychological impairments following critical care. We conducted a focus group study with parents of children surviving pediatric neurocritical care (PNCC) for traumatic brain injury, stroke, meningitis, or encephalitis to determine outcomes important to patients and families, identify barriers to care, and identify potential interventions to improve outcomes. Sixteen parents participated in four groups across Oregon. Three global themes were identified: (1) PNCC is an intense emotional experience for the whole family; (2) PNCC survivorship is a chronic illness; and (3) PNCC has a significant psychological and social impact. Survivors and their families suffer physical, emotional, psychological, cognitive, and social impairments for many years after discharge. Parents in this study highlighted the emotional and psychological distress in survivors and families after PNCC, in contrast to most PNCC research focusing on physical outcomes. Several barriers to care were identified with potential implications on survivor outcomes, including limited pediatric resources in rural settings, perceived lack of awareness of PICS among medical providers, and the substantial financial burden on families. Parents desire improved education surrounding PICS morbidities for families and medical providers, improved communication with primary care providers after discharge, access to educational materials for patients and families, direction to mental health providers, and family support groups to assist them in dealing with morbidities and accessing appropriate resources. Clinicians and researchers should consider the parent perspectives reported here when caring for and evaluating outcomes for children requiring PNCC.

If You Build It, They Will Come: Initial Experience with a Multi-Disciplinary Pediatric Neurocritical Care Follow-Up Clinic.

Pediatric Neurocritical Care diagnoses account for a large proportion of intensive care admissions. Critical care survivors suffer high rates of long-term morbidity, including physical disability, cognitive impairment, and psychosocial dysfunction. To address these morbidities in Pediatric Neurocritical Care survivors, collaboration between Pediatric Neurology and Pediatric Critical Care created a multidisciplinary follow-up clinic providing specialized evaluations after discharge. Clinic referrals apply to all Pediatric Neurocritical Care patients regardless of admission severity of illness. Here, we report an initial case series, which revealed a population that is heterogenous in age, ranging from 1 month to 18 years, and in diagnoses. Traumatic brain injuries of varying severity as well as neuroinfectious and inflammatory diseases accounted for the majority of referrals. Most patients (87%) seen in the clinic had morbidities identified, requiring ongoing evaluation and expansion of the clinic. Cognitive and psychological disturbance were seen in over half of patients at the initial clinic follow-up. Sleep disturbances, daytime fatigue, headache or chronic pain, and vision or hearing concerns were also common at initial follow-up. Data from this initial population of clinic patients reiterates the need for specialized follow-up care, but also highlights the difficulties related to providing this comprehensive care and evaluating interventions to improve outcomes.

Sedation Management in Children Supported on Extracorporeal Membrane Oxygenation for Acute Respiratory Failure.

OBJECTIVES: To describe sedation management in children supported on extracorporeal membrane oxygenation for acute respiratory failure. DESIGN: Secondary analysis of prospectively collected data from a multicenter randomized trial of sedation (Randomized Evaluation of Sedation Titration for Respiratory Failure). SETTING: Twenty-one U.S. PICUs. PATIENTS: One thousand two hundred fifty-five children, 2 weeks to 17 years old, with moderate/severe pediatric acute respiratory distress syndrome. INTERVENTIONS: Sedation managed per usual care or Randomized Evaluation of Sedation Titration for Respiratory Failure protocol. MEASUREMENTS AND MAIN RESULTS: Sixty-one Randomized Evaluation of Sedation Titration for Respiratory Failure patients (5%) with moderate/severe pediatric acute respiratory distress syndrome were supported on extracorporeal membrane oxygenation, including 29 managed per Randomized Evaluation of Sedation Titration for Respiratory Failure protocol. Most extracorporeal membrane oxygenation patients received neuromuscular blockade (46%) or were heavily sedated with State Behavioral Scale scores -3/-2 (34%) by extracorporeal membrane oxygenation day 3. Median opioid and benzodiazepine doses on the day of cannulation, 0.15 mg/kg/hr (3.7 mg/kg/d) and 0.11 mg/kg/hr (2.8 mg/kg/d), increased by 36% and 58%, respectively, by extracorporeal membrane oxygenation day 3. In the 41 patients successfully decannulated prior to study discharge, patients were receiving 0.40 mg/kg/hr opioids (9.7 mg/kg/d) and 0.39 mg/kg/hr benzodiazepines (9.4 mg/kg/d) at decannulation, an increase from cannulation of 108% and 192%, respectively (both p < 0.001). Extracorporeal membrane oxygenation patients experienced more clinically significant iatrogenic withdrawal than moderate/severe pediatric acute respiratory distress syndrome patients managed without extracorporeal membrane oxygenation support (p < 0.001). Compared to extracorporeal membrane oxygenation patients managed per Randomized Evaluation of Sedation Titration for Respiratory Failure protocol, usual care extracorporeal membrane oxygenation patients received more opioids during the study period (mean cumulative dose of 183.0 vs 89.8 mg/kg; p = 0.02), over 6.5 greater exposure days (p = 0.002) with no differences in wakefulness or agitation. CONCLUSIONS: In children, the initiation of extracorporeal membrane oxygenation support is associated with deep sedation, substantial sedative exposure, and increased frequency of iatrogenic withdrawal syndrome. A standardized, goal-directed, nurse-driven sedation protocol may help mitigate these effects.