Association Between Chest Compression Pause Duration and Survival After Pediatric In-Hospital Cardiac Arrest.

BACKGROUND: The association between chest compression (CC) pause duration and pediatric in-hospital cardiac arrest survival outcomes is unknown. The American Heart Association has recommended minimizing pauses in CC in children to <10 seconds, without supportive evidence. We hypothesized that longer maximum CC pause durations are associated with worse survival and neurological outcomes. METHODS: In this cohort study of index pediatric in-hospital cardiac arrests reported in pediRES-Q (Quality of Pediatric Resuscitation in a Multicenter Collaborative) from July of 2015 through December of 2021, we analyzed the association in 5-second increments of the longest CC pause duration for each event with survival and favorable neurological outcome (Pediatric Cerebral Performance Category ≤3 or no change from baseline). Secondary exposures included having any pause >10 seconds or >20 seconds and number of pauses >10 seconds and >20 seconds per 2 minutes. RESULTS: We identified 562 index in-hospital cardiac arrests (median [Q1, Q3] age 2.9 years [0.6, 10.0], 43% female, 13% shockable rhythm). Median length of the longest CC pause for each event was 29.8 seconds (11.5, 63.1). After adjustment for confounders, each 5-second increment in the longest CC pause duration was associated with a 3% lower relative risk of survival with favorable neurological outcome (adjusted risk ratio, 0.97 [95% CI, 0.95-0.99]; P=0.02). Longest CC pause duration was also associated with survival to hospital discharge (adjusted risk ratio, 0.98 [95% CI, 0.96-0.99]; P=0.01) and return of spontaneous circulation (adjusted risk ratio, 0.93 [95% CI, 0.91-0.94]; P<0.001). Secondary outcomes of any pause >10 seconds or >20 seconds and number of CC pauses >10 seconds and >20 seconds were each significantly associated with adjusted risk ratio of return of spontaneous circulation, but not survival or neurological outcomes. CONCLUSIONS: Each 5-second increment in longest CC pause duration during pediatric in-hospital cardiac arrest was associated with lower chance of survival with favorable neurological outcome, survival to hospital discharge, and return of spontaneous circulation. Any CC pause >10 seconds or >20 seconds and number of pauses >10 seconds and >20 seconds were significantly associated with lower adjusted probability of return of spontaneous circulation, but not survival or neurological outcomes.

Associations Between End-Tidal Carbon Dioxide During Pediatric Cardiopulmonary Resuscitation, Cardiopulmonary Resuscitation Quality, and Survival.

BACKGROUND: Supported by laboratory and clinical investigations of adult cardiopulmonary arrest, resuscitation guidelines recommend monitoring end-tidal carbon dioxide (ETCO2) as an indicator of cardiopulmonary resuscitation (CPR) quality, but they note that "specific values to guide therapy have not been established in children." METHODS: This prospective observational cohort study was a National Heart, Lung, and Blood Institute-funded ancillary study of children in the ICU-RESUS trial (Intensive Care Unit-Resuscitation Project; NCT02837497). Hospitalized children (≤18 years of age and ≥37 weeks postgestational age) who received chest compressions of any duration for cardiopulmonary arrest, had an endotracheal or tracheostomy tube at the start of CPR, and evaluable intra-arrest ETCO2 data were included. The primary exposure was event-level average ETCO2 during the first 10 minutes of CPR (dichotomized as ≥20 mm Hg versus <20 mm Hg on the basis of adult literature). The primary outcome was survival to hospital discharge. Secondary outcomes were sustained return of spontaneous circulation, survival to discharge with favorable neurological outcome, and new morbidity among survivors. Poisson regression measured associations between ETCO2 and outcomes as well as the association between ETCO2 and other CPR characteristics: (1) invasively measured systolic and diastolic blood pressures, and (2) CPR quality and chest compression mechanics metrics (ie, time to CPR start; chest compression rate, depth, and fraction; ventilation rate). RESULTS: Among 234 included patients, 133 (57%) had an event-level average ETCO2 ≥20 mm Hg. After controlling for a priori covariates, average ETCO2 ≥20 mm Hg was associated with a higher incidence of survival to hospital discharge (86/133 [65%] versus 48/101 [48%]; adjusted relative risk, 1.33 [95% CI, 1.04-1.69]; P=0.023) and return of spontaneous circulation (95/133 [71%] versus 59/101 [58%]; adjusted relative risk, 1.22 [95% CI, 1.00-1.49]; P=0.046) compared with lower values. ETCO2 ≥20 mm Hg was not associated with survival with favorable neurological outcome or new morbidity among survivors. Average 2 ≥20 mm Hg was associated with higher systolic and diastolic blood pressures during CPR, lower CPR ventilation rates, and briefer pre-CPR arrest durations compared with lower values. Chest compression rate, depth, and fraction did not differ between ETCO2 groups. CONCLUSIONS: In this multicenter study of children with in-hospital cardiopulmonary arrest, ETCO2 ≥20 mm Hg was associated with better outcomes and higher intra-arrest blood pressures, but not with chest compression quality metrics.

Cerebral Oximetry During Pediatric In-Hospital Cardiac Arrest: A Multicenter Study of Survival and Neurologic Outcome.

OBJECTIVES: To determine if near-infrared spectroscopy measuring cerebral regional oxygen saturation (crS o2 ) during cardiopulmonary resuscitation is associated with return of spontaneous circulation (ROSC) and survival to hospital discharge (SHD) in children. DESIGN: Multicenter, observational study. SETTING: Three hospitals in the pediatric Resuscitation Quality (pediRES-Q) collaborative from 2015 to 2022. PATIENTS: Children younger than 18 years, gestational age 37 weeks old or older with in-hospital cardiac arrest (IHCA) receiving cardiopulmonary resuscitation greater than or equal to 1 minute and intra-arrest crS o2 monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was ROSC greater than or equal to 20 minutes without extracorporeal membrane oxygenation. Secondary outcomes included SHD and favorable neurologic outcome (FNO) (Pediatric Cerebral Performance Category 1-2 or no change from prearrest). Among 3212 IHCA events (index and nonindex), 123 met inclusion criteria in 93 patients. Median age was 0.3 years (0.1-1.4 yr) and 31% (38/123) of the cardiopulmonary resuscitation events occurred in patients with cyanotic heart disease. Median cardiopulmonary resuscitation duration was 8 minutes (3-28 min) and ROSC was achieved in 65% (80/123). For index events, SHD was achieved in 59% (54/91) and FNO in 41% (37/91). We determined the association of median intra-arrest crS o2 and percent of crS o2 values above a priori thresholds during the: 1) entire cardiopulmonary resuscitation event, 2) first 5 minutes, and 3) last 5 minutes with ROSC, SHD, and FNO. Higher crS o2 for the entire cardiopulmonary resuscitation event, first 5 minutes, and last 5 minutes were associated with higher likelihood of ROSC, SHD, and FNO. In multivariable analysis of the infant group (age < 1 yr), higher crS o2 was associated with ROSC (odds ratio [OR], 1.06; 95% CI, 1.03-1.10), SHD (OR, 1.04; 95% CI, 1.01-1.07), and FNO (OR, 1.05; 95% CI, 1.02-1.08) after adjusting for presence of cyanotic heart disease. CONCLUSIONS: Higher crS o2 during pediatric IHCA was associated with increased rate of ROSC, SHD, and FNO. Intra-arrest crS o2 may have a role as a real-time, noninvasive predictor of ROSC.

Association of Postarrest Hypotension Burden With Unfavorable Neurologic Outcome After Pediatric Cardiac Arrest.

OBJECTIVE: Quantify hypotension burden using high-resolution continuous arterial blood pressure (ABP) data and determine its association with outcome after pediatric cardiac arrest. DESIGN: Retrospective observational study. SETTING: Academic PICU. PATIENTS: Children 18 years old or younger admitted with in-of-hospital or out-of-hospital cardiac arrest who had invasive ABP monitoring during postcardiac arrest care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: High-resolution continuous ABP was analyzed up to 24 hours after the return of circulation (ROC). Hypotension burden was the time-normalized integral area between mean arterial pressure (MAP) and fifth percentile MAP for age. The primary outcome was unfavorable neurologic status (pediatric cerebral performance category ≥ 3 with change from baseline) at hospital discharge. Mann-Whitney U tests compared hypotension burden, duration, and magnitude between favorable and unfavorable patients. Multivariable logistic regression determined the association of unfavorable outcomes with hypotension burden, duration, and magnitude at various percentile thresholds from the 5th through 50th percentile for age. Of 140 patients (median age 53 [interquartile range 11-146] mo, 61% male); 63% had unfavorable outcomes. Monitoring duration was 21 (7-24) hours. Using a MAP threshold at the fifth percentile for age, the median hypotension burden was 0.01 (0-0.11) mm Hg-hours per hour, greater for patients with unfavorable compared with favorable outcomes (0 [0-0.02] vs. 0.02 [0-0.27] mm Hg-hr per hour, p < 0.001). Hypotension duration and magnitude were greater for unfavorable compared with favorable patients (0.03 [0-0.77] vs. 0.71 [0-5.01]%, p = 0.003; and 0.16 [0-1.99] vs. 2 [0-4.02] mm Hg, p = 0.001). On logistic regression, a 1-point increase in hypotension burden below the fifth percentile for age (equivalent to 1 mm Hg-hr of burden per hour of recording) was associated with increased odds of unfavorable outcome (adjusted odds ratio [aOR] 14.8; 95% CI, 1.1-200; p = 0.040). At MAP thresholds of 10th-50th percentiles for age, MAP burden below the threshold was greater in unfavorable compared with favorable patients in a dose-dependent manner. CONCLUSIONS: High-resolution continuous ABP data can be used to quantify hypotension burden after pediatric cardiac arrest. The burden, duration, and magnitude of hypotension are associated with unfavorable neurologic outcomes.

Epinephrine Dosing Intervals Are Associated With Pediatric In-Hospital Cardiac Arrest Outcomes: A Multicenter Study.

OBJECTIVES: Data to support epinephrine dosing intervals during cardiopulmonary resuscitation (CPR) are conflicting. The objective of this study was to evaluate the association between epinephrine dosing intervals and outcomes. We hypothesized that dosing intervals less than 3 minutes would be associated with improved neurologic survival compared with greater than or equal to 3 minutes. DESIGN: This study is a secondary analysis of The ICU-RESUScitation Project (NCT028374497), a multicenter trial of a quality improvement bundle of physiology-directed CPR training and post-cardiac arrest debriefing. SETTING: Eighteen PICUs and pediatric cardiac ICUs in the United States. PATIENTS: Subjects were 18 years young or younger and 37 weeks old or older corrected gestational age who had an index cardiac arrest. Patients who received less than two doses of epinephrine, received extracorporeal CPR, or had dosing intervals greater than 8 minutes were excluded. INTERVENTIONS: The primary exposure was an epinephrine dosing interval of less than 3 vs. greater than or equal to 3 minutes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was survival to discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1-2 or no change from baseline. Regression models evaluated the association between dosing intervals and: 1) survival outcomes and 2) CPR duration. Among 382 patients meeting inclusion and exclusion criteria, median age was 0.9 years (interquartile range 0.3-7.6 yr) and 45% were female. After adjustment for confounders, dosing intervals less than 3 minutes were not associated with survival with favorable neurologic outcome (adjusted relative risk [aRR], 1.10; 95% CI, 0.84-1.46; p = 0.48) but were associated with improved sustained return of spontaneous circulation (ROSC) (aRR, 1.21; 95% CI, 1.07-1.37; p < 0.01) and shorter CPR duration (adjusted effect estimate, -9.5 min; 95% CI, -14.4 to -4.84 min; p < 0.01). CONCLUSIONS: In patients receiving at least two doses of epinephrine, dosing intervals less than 3 minutes were not associated with neurologic outcome but were associated with sustained ROSC and shorter CPR duration.

Early bolus epinephrine administration during pediatric cardiopulmonary resuscitation for bradycardia with poor perfusion: an ICU-resuscitation study.

BACKGROUND: Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness. METHODS: Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (< 19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016-March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status. RESULTS: Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness and vasoactive-inotrope scores. Early epinephrine was not associated with survival to discharge (aRR 0.97, 95%CI 0.82, 1.14) or survival with favorable neurologic outcome (aRR 0.99, 95%CI 0.82, 1.18). Among 186 patients with invasive blood pressure waveforms, 118 (63%) had at least 1 period of pulselessness during the first 10 min of CPR; 86 (46%) by 2 min and 100 (54%) by 3 min. Sustained return of spontaneous circulation was highest after bradycardia with poor perfusion (84%) compared to bradycardia with poor perfusion progressing to pulselessness (43%) and bradycardia with poor perfusion progressing to pulselessness followed by return to bradycardia with poor perfusion (62%) (p < 0.001). CONCLUSIONS: In this cohort of pediatric CPR events with an initial rhythm of bradycardia with poor perfusion, we failed to identify an association between early bolus epinephrine and outcomes when controlling for illness severity. Most children receiving CPR for bradycardia with poor perfusion developed subsequent pulselessness, 46% within 2 min of CPR onset.

Evaluating Airway Management in Patients With Trisomy 21 in the PICU and Cardiac ICU: A Retrospective Cohort Study.

OBJECTIVES: Children with trisomy 21 often have anatomic and physiologic features that may complicate tracheal intubation (TI). TI in critically ill children with trisomy 21 is not well described. We hypothesize that in children with trisomy 21, TI is associated with greater odds of adverse airway outcomes (AAOs), including TI-associated events (TIAEs), and peri-intubation hypoxemia (defined as > 20% decrease in pulse oximetry saturation [Sp o2 ]). DESIGN: Retrospective database study using the National Emergency Airway Registry for Children (NEAR4KIDS). SETTING: Registry data from 16 North American PICUs and cardiac ICUs (CICUs), from January 2014 to December 2020. PATIENTS: A cohort of children under 18 years old who underwent TI in the PICU or CICU from in a NEAR4KIDS center. We identified patients with trisomy 21 and selected matched cohorts within the registry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 8401 TIs in the registry dataset. Children with trisomy 21 accounted for 274 (3.3%) TIs. Among those with trisomy 21, 84% had congenital heart disease and 4% had atlantoaxial instability. Cervical spine protection was used in 6%. The diagnosis of trisomy 21 (vs. without) was associated with lower median weight 7.8 (interquartile range [IQR] 4.5-14.7) kg versus 10.6 (IQR 5.2-25) kg ( p < 0.001), and more higher percentage undergoing TI for oxygenation (46% vs. 32%, p < 0.001) and ventilation failure (41% vs. 35%, p = 0.04). Trisomy 21 patients had more difficult airway features (35% vs. 25%, p = 0.001), including upper airway obstruction (14% vs. 8%, p = 0.001). In addition, a greater percentage of trisomy 21 patients received atropine (34% vs. 26%, p = 0.004); and, lower percentage were intubated with video laryngoscopy (30% vs. 37%, p = 0.023). After 1:10 (trisomy 21:controls) propensity-score matching, we failed to identify an association difference in AAO rates (absolute risk difference -0.6% [95% CI -6.1 to 4.9], p = 0.822). CONCLUSIONS: Despite differences in airway risks and TI approaches, we have not identified an association between the diagnosis of trisomy 21 and higher AAOs.

Survival With Favorable Neurologic Outcome and Quality of Cardiopulmonary Resuscitation Following In-Hospital Cardiac Arrest in Children With Cardiac Disease Compared With Noncardiac Disease.

OBJECTIVES: To assess associations between outcome and cardiopulmonary resuscitation (CPR) quality for in-hospital cardiac arrest (IHCA) in children with medical cardiac, surgical cardiac, or noncardiac disease. DESIGN: Secondary analysis of a multicenter cluster randomized trial, the ICU-RESUScitation Project (NCT02837497, 2016-2021). SETTING: Eighteen PICUs. PATIENTS: Children less than or equal to 18 years old and greater than or equal to 37 weeks postconceptual age receiving chest compressions (CC) of any duration during the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,100 children with IHCA, there were 273 medical cardiac (25%), 383 surgical cardiac (35%), and 444 noncardiac (40%) cases. Favorable neurologic outcome was defined as no more than moderate disability or no worsening from baseline Pediatric Cerebral Performance Category at discharge. The medical cardiac group had lower odds of survival with favorable neurologic outcomes compared with the noncardiac group (48% vs 55%; adjusted odds ratio [aOR] [95% CI], aOR 0.59 [95% CI, 0.39-0.87], p = 0.008) and surgical cardiac group (48% vs 58%; aOR 0.64 [95% CI, 0.45-0.9], p = 0.01). We failed to identify a difference in favorable outcomes between surgical cardiac and noncardiac groups. We also failed to identify differences in CC rate, CC fraction, ventilation rate, intra-arrest average target diastolic or systolic blood pressure between medical cardiac versus noncardiac, and surgical cardiac versus noncardiac groups. The surgical cardiac group had lower odds of achieving target CC depth compared to the noncardiac group (OR 0.15 [95% CI, 0.02-0.52], p = 0.001). We failed to identify a difference in the percentage of patients achieving target CC depth when comparing medical cardiac versus noncardiac groups. CONCLUSIONS: In pediatric IHCA, medical cardiac patients had lower odds of survival with favorable neurologic outcomes compared with noncardiac and surgical cardiac patients. We failed to find differences in CPR quality between medical cardiac and noncardiac patients, but there were lower odds of achieving target CC depth in surgical cardiac compared to noncardiac patients.

Early Cardiac Arrest Hemodynamics, End-Tidal C o2 , and Outcome in Pediatric Extracorporeal Cardiopulmonary Resuscitation: Secondary Analysis of the ICU-RESUScitation Project Dataset (2016-2021).

OBJECTIVES: Cannulation for extracorporeal membrane oxygenation during active extracorporeal cardiopulmonary resuscitation (ECPR) is a method to rescue patients refractory to standard resuscitation. We hypothesized that early arrest hemodynamics and end-tidal C o2 (ET co2 ) are associated with survival to hospital discharge with favorable neurologic outcome in pediatric ECPR patients. DESIGN: Preplanned, secondary analysis of pediatric Utstein, hemodynamic, and ventilatory data in ECPR patients collected during the 2016-2021 Improving Outcomes from Pediatric Cardiac Arrest study; the ICU-RESUScitation Project (ICU-RESUS; NCT02837497). SETTING: Eighteen ICUs participated in ICU-RESUS. PATIENTS: There were 97 ECPR patients with hemodynamic waveforms during cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 71 of 97 patients (73%) were younger than 1 year old, 82 of 97 (85%) had congenital heart disease, and 62 of 97 (64%) were postoperative cardiac surgical patients. Forty of 97 patients (41%) survived with favorable neurologic outcome. We failed to find differences in diastolic or systolic blood pressure, proportion achieving age-based target diastolic or systolic blood pressure, or chest compression rate during the initial 10 minutes of CPR between patients who survived with favorable neurologic outcome and those who did not. Thirty-five patients had ET co2 data; of 17 survivors with favorable neurologic outcome, four of 17 (24%) had an average ET co2 less than 10 mm Hg and two (12%) had a maximum ET co2 less than 10 mm Hg during the initial 10 minutes of resuscitation. CONCLUSIONS: We did not identify an association between early hemodynamics achieved by high-quality CPR and survival to hospital discharge with favorable neurologic outcome after pediatric ECPR. Candidates for ECPR with ET co2 less than 10 mm Hg may survive with favorable neurologic outcome.

Adverse Tracheal Intubation Events in Critically Ill Underweight and Obese Children: Retrospective Study of the National Emergency Airway for Children Registry (2013-2020).

OBJECTIVES: Extremes of patient body mass index are associated with difficult intubation and increased morbidity in adults. We aimed to determine the association between being underweight or obese with adverse airway outcomes, including adverse tracheal intubation (TI)-associated events (TIAEs) and/or severe peri-intubation hypoxemia (pulse oximetry oxygen saturation < 80%) in critically ill children. DESIGN/SETTING: Retrospective cohort using the National Emergency Airway for Children registry dataset of 2013-2020. PATIENTS: Critically ill children, 0 to 17 years old, undergoing TI in PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Registry data from 24,342 patients who underwent TI between 2013 and 2020 were analyzed. Patients were categorized using the Centers for Disease Control and Prevention weight-for-age chart: normal weight (5th-84th percentile) 57.1%, underweight (< 5th percentile) 27.5%, overweight (85th to < 95th percentile) 7.2%, and obese (≥ 95th percentile) 8.2%. Underweight was most common in infants (34%); obesity was most common in children older than 8 years old (15.1%). Underweight patients more often had oxygenation and ventilation failure (34.0%, 36.2%, respectively) as the indication for TI and a history of difficult airway (16.7%). Apneic oxygenation was used more often in overweight and obese patients (19.1%, 19.6%) than in underweight or normal weight patients (14.1%, 17.1%; p < 0.001). TIAEs and/or hypoxemia occurred more often in underweight (27.1%) and obese (24.3%) patients ( p < 0.001). TI in underweight children was associated with greater odds of adverse airway outcome compared with normal weight children after adjusting for potential confounders (underweight: adjusted odds ratio [aOR], 1.09; 95% CI, 1.01-1.18; p = 0.016). Both underweight and obesity were associated with hypoxemia after adjusting for covariates and site clustering (underweight: aOR, 1.11; 95% CI, 1.02-1.21; p = 0.01 and obesity: aOR, 1.22; 95% CI, 1.07-1.39; p = 0.002). CONCLUSIONS: In underweight and obese children compared with normal weight children, procedures around the timing of TI are associated with greater odds of adverse airway events.

Evaluation of Automated Finger Compression for Capillary Refill Time Measurement in Pediatrics.

OBJECTIVES: Early shock reversal is crucial to improve patient outcomes. Capillary refill time (CRT) is clinically important to identify and monitor shock in children but has issues with inconsistency. To minimize inconsistency, we evaluated a CRT monitoring system using an automated compression device. Our objective was to determine proper compression pressure in children. METHODS: Clinician force for CRT was collected during manual CRT measurement as a reference for automated compression in a previous study (12.9 N, 95% confidence interval, 12.5-13.4; n = 454). An automated compression device with a soft inflation bladder was fitted with a force sensor. We evaluated the effectiveness of the automated pressure to eliminate pulsatile blood flow from the distal phalange. Median and variance of CRT analysis at each pressure was compared. RESULTS: A comparison of pressures at 300 to 500 mm Hg on a simulated finger yielded a force of 5 to 10 N, and these pressures were subsequently used for automated compression for CRT. Automated compression was tested in 44 subjects (median age, 33 months; interquartile range [IQR], 14-56 months). At interim analysis of 17 subjects, there was significant difference in the waveform with residual pulsatile blood flow (9/50: 18% at 300 mm Hg, 5/50:10% at 400 mm Hg, 0/51: 0% at 500 mm Hg, P = 0.008). With subsequent enrollment of 27 subjects at 400 and 500 mm Hg, none had residual pulsatile blood flow. There was no difference in the CRT: median 1.8 (IQR, 1.06-2.875) in 400 mm Hg vs median 1.87 (IQR, 1.25-2.8325) in 500 mm Hg, P = 0.81. The variance of CRT was significantly larger in 400 mm Hg: 2.99 in 400 mm Hg vs. 1.35 in 500 mm Hg, P = 0.02, Levene's test. Intraclass correlation coefficient for automated CRT was 0.56 at 400 mm Hg and 0.78 at 500 mm Hg. CONCLUSIONS: Using clinician CRT measurement data, we determined either 400 or 500 mm Hg is an appropriate pressure for automated CRT, although 500 mm Hg demonstrates superior consistency.

Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial.

OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution ( n = 351) versus 0.9% saline ( n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3-9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49-0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusion-related AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization.

Diastolic Blood Pressure Threshold During Pediatric Cardiopulmonary Resuscitation and Survival Outcomes: A Multicenter Validation Study.

OBJECTIVES: Arterial diastolic blood pressure (DBP) greater than 25 mm Hg in infants and greater than 30 mm Hg in children greater than 1 year old during cardiopulmonary resuscitation (CPR) was associated with survival to hospital discharge in one prospective study. We sought to validate these potential hemodynamic targets in a larger multicenter cohort. DESIGN: Prospective observational study. SETTING: Eighteen PICUs in the ICU-RESUScitation prospective trial from October 2016 to March 2020. PATIENTS: Children less than or equal to 18 years old with CPR greater than 30 seconds and invasive blood pressure (BP) monitoring during CPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Invasive BP waveform data and Utstein-style CPR data were collected, including prearrest patient characteristics, intra-arrest interventions, and outcomes. Primary outcome was survival to hospital discharge, and secondary outcomes were return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Multivariable Poisson regression models with robust error estimates evaluated the association of DBP greater than 25 mm Hg in infants and greater than 30 mm Hg in older children with these outcomes. Among 1,129 children with inhospital cardiac arrests, 413 had evaluable DBP data. Overall, 85.5% of the patients attained thresholds of mean DBP greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in older children. Initial return of circulation occurred in 91.5% and 25% by placement on extracorporeal membrane oxygenator. Survival to hospital discharge occurred in 58.6%, and survival with favorable neurologic outcome in 55.4% (i.e. 94.6% of survivors had favorable neurologic outcomes). Mean DBP greater than 25 mm Hg for infants and greater than 30 mm Hg for older children was significantly associated with survival to discharge (adjusted relative risk [aRR], 1.32; 1.01-1.74; p = 0.03) and ROSC (aRR, 1.49; 1.12-1.97; p = 0.002) but did not reach significance for survival to hospital discharge with favorable neurologic outcome (aRR, 1.30; 0.98-1.72; p = 0.051). CONCLUSIONS: These validation data demonstrate that achieving mean DBP during CPR greater than 25 mm Hg for infants and greater than 30 mm Hg for older children is associated with higher rates of survival to hospital discharge, providing potential targets for DBP during CPR.

Interventions to promote cost-effectiveness in adult intensive care units: consensus statement and considerations for best practice from a multidisciplinary and multinational eDelphi study.

BACKGROUND: There is limited evidence to guide interventions that promote cost-effectiveness in adult intensive care units (ICU). The aim of this consensus statement is to identify globally applicable interventions for best ICU practice and provide guidance for judicious use of resources. METHODS: A three-round modified online Delphi process, using a web-based platform, sought consensus from 61 multidisciplinary ICU experts (physicians, nurses, allied health, administrators) from 21 countries. Round 1 was qualitative to ascertain opinions on cost-effectiveness criteria based on four key domains of high-value healthcare (foundational elements; infrastructure fundamentals; care delivery priorities; reliability and feedback). Round 2 was qualitative and quantitative, while round 3 was quantitative to reiterate and establish criteria. Both rounds 2 and 3 utilized a five-point Likert scale for voting. Consensus was considered when > 70% of the experts voted for a proposed intervention. Thereafter, the steering committee endorsed interventions that were identified as 'critical' by more than 50% of steering committee members. These interventions and experts' comments were summarized as final considerations for best practice. RESULTS: At the conclusion of round 3, consensus was obtained on 50 best practice considerations for cost-effectiveness in adult ICU. Finally, the steering committee endorsed 9 'critical' best practice considerations. This included adoption of a multidisciplinary ICU model of care, focus on staff training and competency assessment, ongoing quality audits, thus ensuring high quality of critical care services whether within or outside the four walls of ICUs, implementation of a dynamic staff roster, multidisciplinary approach to implementing end-of-life care, early mobilization and promoting international consensus efforts on the Green ICU concept. CONCLUSIONS: This Delphi study with international experts resulted in 9 consensus statements and best practice considerations promoting cost-effectiveness in adult ICUs. Stakeholders (government bodies, professional societies) must lead the efforts to identify locally applicable specifics while working within these best practice considerations with the available resources.

The physiologic response to epinephrine and pediatric cardiopulmonary resuscitation outcomes.

BACKGROUND: Epinephrine is provided during cardiopulmonary resuscitation (CPR) to increase systemic vascular resistance and generate higher diastolic blood pressure (DBP) to improve coronary perfusion and attain return of spontaneous circulation (ROSC). The DBP response to epinephrine during pediatric CPR and its association with outcomes have not been well described. Thus, the objective of this study was to measure the association between change in DBP after epinephrine administration during CPR and ROSC. METHODS: This was a prospective multicenter study of children receiving ≥ 1 min of CPR with ≥ 1 dose of epinephrine and evaluable invasive arterial BP data in the 18 ICUs of the ICU-RESUS trial (NCT02837497). Blood pressure waveforms underwent compression-by-compression quantitative analysis. The mean DBP before first epinephrine dose was compared to mean DBP two minutes post-epinephrine. Patients with ≥ 5 mmHg increase in DBP were characterized as "responders." RESULTS: Among 147 patients meeting inclusion criteria, 66 (45%) were characterized as responders and 81 (55%) were non-responders. The mean increase in DBP with epinephrine was 4.4 [- 1.9, 11.5] mmHg (responders: 13.6 [7.5, 29.3] mmHg versus non-responders: - 1.5 [- 5.0, 1.5] mmHg; p < 0.001). After controlling for a priori selected covariates, epinephrine response was associated with ROSC (aRR 1.60 [1.21, 2.12]; p = 0.001). Sensitivity analyses identified similar associations between DBP response thresholds of ≥ 10, 15, and 20 mmHg and ROSC; DBP responses of ≥ 10 and ≥ 15 mmHg were associated with higher aRR of survival to hospital discharge and survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score of 1-3 or no worsening from baseline). CONCLUSIONS: The change in DBP following epinephrine administration during pediatric in-hospital CPR was associated with return of spontaneous circulation.

Whole blood transcriptomics identifies subclasses of pediatric septic shock.

BACKGROUND: Sepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles. METHODS: The subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses. RESULTS: Patients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells and less diverse T cell receptor repertoires. CONCLUSIONS: Two subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences. Trial Registration This is a secondary analysis of data generated as part of the observational CAF-PINT ancillary of the HALF-PINT study (NCT01565941). Registered March 29, 2012.

Identification of post-cardiac arrest blood pressure thresholds associated with outcomes in children: an ICU-Resuscitation study.

INTRODUCTION: Though early hypotension after pediatric in-hospital cardiac arrest (IHCA) is associated with inferior outcomes, ideal post-arrest blood pressure (BP) targets have not been established. We aimed to leverage prospectively collected BP data to explore the association of post-arrest BP thresholds with outcomes. We hypothesized that post-arrest systolic and diastolic BP thresholds would be higher than the currently recommended post-cardiopulmonary resuscitation BP targets and would be associated with higher rates of survival to hospital discharge. METHODS: We performed a secondary analysis of prospectively collected BP data from the first 24 h following return of circulation from index IHCA events enrolled in the ICU-RESUScitation trial (NCT02837497). The lowest documented systolic BP (SBP) and diastolic BP (DBP) were percentile-adjusted for age, height and sex. Receiver operator characteristic curves and cubic spline analyses controlling for illness category and presence of pre-arrest hypotension were generated exploring the association of lowest post-arrest SBP and DBP with survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category of 1-3 or no change from baseline). Optimal cutoffs for post-arrest BP thresholds were based on analysis of receiver operator characteristic curves and spline curves. Logistic regression models accounting for illness category and pre-arrest hypotension examined the associations of these thresholds with outcomes. RESULTS: Among 693 index events with 0-6 h post-arrest BP data, identified thresholds were: SBP > 10th percentile and DBP > 50th percentile for age, sex and height. Fifty-one percent (n = 352) of subjects had lowest SBP above threshold and 50% (n = 346) had lowest DBP above threshold. SBP and DBP above thresholds were each associated with survival to hospital discharge (SBP: aRR 1.21 [95% CI 1.10, 1.33]; DBP: aRR 1.23 [1.12, 1.34]) and survival to hospital discharge with favorable neurologic outcome (SBP: aRR 1.22 [1.10, 1.35]; DBP: aRR 1.27 [1.15, 1.40]) (all p < 0.001). CONCLUSIONS: Following pediatric IHCA, subjects had higher rates of survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome when BP targets above a threshold of SBP > 10th percentile for age and DBP > 50th percentile for age during the first 6 h post-arrest.

Inappropriate Shock Delivery Is Common During Pediatric In-Hospital Cardiac Arrest.

OBJECTIVES: To characterize inappropriate shock delivery during pediatric in-hospital cardiac arrest (IHCA). DESIGN: Retrospective cohort study. SETTING: An international pediatric cardiac arrest quality improvement collaborative Pediatric Resuscitation Quality [pediRES-Q]. PATIENTS: All IHCA events from 2015 to 2020 from the pediRES-Q Collaborative for which shock and electrocardiogram waveform data were available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 418 shocks delivered during 159 cardiac arrest events, with 381 shocks during 158 events at 28 sites remaining after excluding undecipherable rhythms. We classified shocks as: 1) appropriate (ventricular fibrillation [VF] or wide complex ≥ 150/min); 2) indeterminate (narrow complex ≥ 150/min or wide complex 100-149/min); or 3) inappropriate (asystole, sinus, narrow complex < 150/min, or wide complex < 100/min) based on the rhythm immediately preceding shock delivery. Of delivered shocks, 57% were delivered appropriately for VF or wide complex rhythms with a rate greater than or equal to 150/min. Thirteen percent were classified as indeterminate. Thirty percent were delivered inappropriately for asystole (6.8%), sinus (3.1%), narrow complex less than 150/min (11%), or wide complex less than 100/min (8.9%) rhythms. Eighty-eight percent of all shocks were delivered in ICUs or emergency departments, and 30% of those were delivered inappropriately. CONCLUSIONS: The rate of inappropriate shock delivery for pediatric IHCA in this international cohort is at least 30%, with 23% delivered to an organized electrical rhythm, identifying opportunity for improvement in rhythm identification training.

Nonpulmonary Treatments for Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: To provide an updated review of the literature on nonpulmonary treatments for pediatric acute respiratory distress syndrome (PARDS) from the Second Pediatric Acute Lung Injury Consensus Conference. DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: Searches were limited to children with PARDS or hypoxic respiratory failure focused on nonpulmonary adjunctive therapies (sedation, delirium management, neuromuscular blockade, nutrition, fluid management, transfusion, sleep management, and rehabilitation). DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Twenty-five studies were identified for full-text extraction. Five clinical practice recommendations were generated, related to neuromuscular blockade, nutrition, fluid management, and transfusion. Thirteen good practice statements were generated on the use of sedation, iatrogenic withdrawal syndrome, delirium, sleep management, rehabilitation, and additional information on neuromuscular blockade and nutrition. Three research statements were generated to promote further investigation in nonpulmonary therapies for PARDS. CONCLUSIONS: These recommendations and statements about nonpulmonary treatments in PARDS are intended to promote optimization and consistency of care for patients with PARDS and identify areas of uncertainty requiring further investigation.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.