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.

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.

Outcomes of Extracorporeal Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest Among Children With Noncardiac Illness Categories.

OBJECTIVES: The objective of this study was to determine the association of the use of extracorporeal cardiopulmonary resuscitation (ECPR) with survival to hospital discharge in pediatric patients with a noncardiac illness category. A secondary objective was to report on trends in ECPR usage in this population for 20 years. DESIGN: Retrospective multicenter cohort study. SETTING: Hospitals contributing data to the American Heart Association's Get With The Guidelines-Resuscitation registry between 2000 and 2021. PATIENTS: Children (<18 yr) with noncardiac illness category who received greater than or equal to 30 minutes of cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Propensity score weighting balanced ECPR and conventional CPR (CCPR) groups on hospital and patient characteristics. Multivariable logistic regression incorporating these scores tested the association of ECPR with survival to discharge. A Bayesian logistic regression model estimated the probability of a positive effect from ECPR. A secondary analysis explored temporal trends in ECPR utilization. Of 875 patients, 159 received ECPR and 716 received CCPR. The median age was 1.0 [interquartile range: 0.2-7.0] year. Most patients (597/875; 68%) had a primary diagnosis of respiratory insufficiency. Median CPR duration was 45 [35-63] minutes. ECPR use increased over time ( p < 0.001). We did not identify differences in survival to discharge between the ECPR group (21.4%) and the CCPR group (16.2%) in univariable analysis ( p = 0.13) or propensity-weighted multivariable logistic regression (adjusted odds ratio 1.42 [95% CI, 0.84-2.40; p = 0.19]). The Bayesian model estimated an 85.1% posterior probability of a positive effect of ECPR on survival to discharge. CONCLUSIONS: ECPR usage increased substantially for the last 20 years. We failed to identify a significant association between ECPR and survival to hospital discharge, although a post hoc Bayesian analysis suggested a survival benefit (85% posterior probability).

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.

Evolution and Impact of a Diagnostic Point-of-Care Ultrasound Program in a PICU.

OBJECTIVES: To evaluate the impact of point-of-care ultrasound (POCUS) use on clinicians within a PICU and to assess infrastructural elements of our POCUS program development. DESIGN: Retrospective observational study. SETTING: Large academic, noncardiac PICU in the United States. SUBJECTS: Patients in a PICU who had diagnostic POCUS performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between January 1, 2017, and December 31, 2022, 7201 diagnostic POCUS studies were ordered; 1930 (26.8%) had a quality assurance (QA) record generated in an independent POCUS QA database. The cardiac domain was most frequently imaged (81.0% of ordered studies, 81.2% of reviewed studies). POCUS images changed clinician understanding of pathophysiology in 563 of 1930 cases (29.2%); when this occurred, management was changed in 318 of 563 cases (56.5%). Cardiac POCUS studies altered clinician suspected pathophysiology in 30.1% of cases (472/1568), compared with 21.5% (91/362) in noncardiac studies (p = 0.06). Among cases where POCUS changed clinician understanding, management changed more often following cardiac than noncardiac POCUS (p = 0.02). Clinicians identified a need for cardiology consultation or complete echocardiograms in 294 of 1568 cardiac POCUS studies (18.8%). Orders for POCUS imaging increased by 94.9%, and revenue increased by 159.4%, from initial to final study year. QA database use by both clinicians and reviewers decreased annually as QA processes evolved in the setting of technologic growth and unit expansion. CONCLUSIONS: Diagnostic POCUS imaging in the PICU frequently yields information that alters diagnosis and changes management. As PICU POCUS use increased, QA processes evolved resulting in decreased use of our initial QA database. Modifications to QA processes are likely necessary as clinical contexts change over time.

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.

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.

Defined, low threshold for caesarean section and multidisciplinary team management improves fetal outcome from acute pancreatitis in pregnancy.

BACKGROUND: Acute pancreatitis in pregnancy (APIP) is associated with increased maternal and fetal mortality. OBJECTIVES: We sought to determine whether a low threshold for cesarean section (C-section) in severe acute pancreatitis (SAP) or Predict SAP improves maternal and fetal outcomes in patients with APIP. METHODS: We identified patients with APIP at a single institution from a prospective database and studied fetal and maternal health in APIP before (2005-2014) and after (2015-2019) introduction of multidisciplinary team management with a defined, lowered threshold for C-section. The primary end point was fetal mortality comprising abortion and perinatal death. Risk factors associated with fetal mortality were analyzed by univariable and multivariable logistic regression analysis. RESULTS: A total of 165 patients with APIP were eligible for analysis. There was a highly significant increase in patients undergoing C-section from 37 (30.8%) of 120 during 2005-2014 to 27 (60%) of 45 in 2015-2019 (P = 0.001), with a highly significant fall in fetal mortality from 37 (30.8%) of 120 to 3 (6.7%) of 45 between the same periods (P = 0.001), when maternal mortality fell from 6 to zero (P = 0.19). Maternal early systemic inflammatory response syndrome (SIRS) (odds ratio [OR] 6.98, 95% confidence interval [CI] 1.53, 30.80, P = 0.01) and SAP (OR 3.64, 95%CI 1.25, 10.60, P = 0.02) were two independent risk factors associated with fetal mortality. CONCLUSIONS: Multidisciplinary collaboration and a defined, low threshold for C-section improve fetal outcomes in patients with APIP.

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.

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.

Predicting Persistent Acute Respiratory Failure in Acute Pancreatitis: The Accuracy of Two Lung Injury Indices.

BACKGROUND/AIMS: Early and accurate identification of patients with acute pancreatitis (AP) at high risk of persistent acute respiratory failure (PARF) is crucial. We sought to determine the accuracy of simplified Lung Injury Prediction Score (sLIPS) and simplified Early Acute Lung Injury (sEALI) for predicting PARF in ward AP patients. METHODS: Consecutive AP patients in a training cohort from West China Hospital of Sichuan University (n = 912) and a validation cohort from The First Affiliated Hospital of Nanchang University (n = 1033) were analyzed. PARF was defined as oxygen in arterial blood/fraction of inspired oxygen < 300 mmHg that lasts for > 48 h. The sLIPS was composed by shock (predisposing condition), alcohol abuse, obesity, high respiratory rate, low oxygen saturation, high oxygen requirement, hypoalbuminemia, and acidosis (risk modifiers). The sEALI was calculated from oxygen 2 to 6 L/min, oxygen > 6 L/min, and high respiratory rate. Both indices were calculated on admission. RESULTS: PARF developed in 16% (145/912) and 22% (228/1033) (22%) of the training and validation cohorts, respectively. In these patients, sLIPS and sEALI were significantly increased. sLIPS ≥ 2 predicted PARF in the training (AUROC 0.87, 95% CI 0.84-0.89) and validation (AUROC 0.81, 95% CI 0.78-0.83) cohorts. sLIPS was significantly more accurate than sEALI and current clinical scoring systems in both cohorts (all P < 0.05). CONCLUSIONS: Using routinely available clinical data, the sLIPS can accurately predict PARF in ward AP patients and outperforms the sEALI and current existing clinical scoring systems.

A microRNA checkpoint for Ca2+ signaling and overload in acute pancreatitis.

Acute pancreatitis (AP) is a common digestive disease without specific treatment, and its pathogenesis features multiple deleterious amplification loops dependent on translation, triggered by cytosolic Ca2+ ([Ca2+]i) overload; however, the underlying mechanisms in Ca2+ overload of AP remains incompletely understood. Here we show that microRNA-26a (miR-26a) inhibits pancreatic acinar cell (PAC) store-operated Ca2+ entry (SOCE) channel expression, Ca2+ overload, and AP. We find that major SOCE channels are post-transcriptionally induced in PACs during AP, whereas miR-26a expression is reduced in experimental and human AP and correlated with AP severity. Mechanistically, miR-26a simultaneously targets Trpc3 and Trpc6 SOCE channels and attenuates physiological oscillations and pathological elevations of [Ca2+]i in PACs. MiR-26a deficiency increases SOCE channel expression and [Ca2+]i overload, and significantly exacerbates AP. Conversely, global or PAC-specific overexpression of miR-26a in mice ameliorates pancreatic edema, neutrophil infiltration, acinar necrosis, and systemic inflammation, accompanied with remarkable improvements on pathological determinants related with [Ca2+]i overload. Moreover, pancreatic or systemic administration of an miR-26a mimic to mice significantly alleviates experimental AP. These findings reveal a previously unknown mechanism underlying AP pathogenesis, establish a critical role for miR-26a in Ca2+ signaling in the exocrine pancreas, and identify a potential target for the treatment of AP.

Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19.

Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 is a potentially life-threatening contagious disease spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More severe forms of both diseases exhibit commonalities with dysregulated immune responses resulting in amplified inflammation and susceptibility to infection. Human leucocyte antigen (HLA)-DR, expressed on antigen-presenting cells, acts as an indicator of immune function. Research advances have highlighted the predictive values of monocytic HLA-DR (mHLA-DR) expression for disease severity and infectious complications in both acute pancreatitis and COVID-19 patients. While the regulatory mechanism of altered mHLA-DR expression remains unclear, HLA-DR-/low monocytic myeloid-derived suppressor cells are potent drivers of immunosuppression and poor outcomes in these diseases. Future studies with mHLA-DR-guided enrollment or targeted immunotherapy are warranted in more severe cases of patients with acute pancreatitis and COVID-19.

Insulin or blood purification treatment for hypertriglyceridaemia-associated acute pancreatitis: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Hypertriglyceridaemia increases risks from acute pancreatitis (HTG-AP) over other aetiologies, but optimal management for HTG-AP remains undefined. We performed a systematic review and meta-analysis of studies of insulin-based treatment (IT) versus blood purification treatment (BPT) for HTG-AP. METHODS: Searches were conducted to identify randomised trials and observational studies published between 1946 and 2022 that compared IT and BPT for HTG-AP reporting baseline and post-treatment serum triglyceride (TG) levels with clinical outcomes. The primary outcome was serum TG reduction (Δ-TG) from baseline while secondary outcomes included complications, length of stay, adverse events, and cost. RESULTS: Fifteen (1 randomised, 2 prospective case-controlled, and 12 retrospective cohort) studies were analysed comprising 909 cases with HTG-AP. Pooled results demonstrated IT was significantly less efficient than BPT in Δ-TG at 24 h (WMD -666.06, 95% CI -1130.18 to -201.94, P = 0.005; 12 studies), at 48 h (WMD -672.60, 95% CI -1233.44 to -111.77; 8 studies), and overall Δ-TG by day 7 (WMD -385.81, 95% CI -711.07 to -60.54; 8 studies) (both P = 0.02). IT, however, was associated with significantly fewer adverse events (OR 0.09, 95% CI 0.03 to 0.27, P < 0.0001; 7 studies) and significantly reduced cost (WMD -2.50, 95% CI -3.61 to -1.39, P < 0.00001; 3 studies). Other secondary outcomes were not significantly different between the two regimens (all P ≥ 0.11). In subgroup analysis Δ-TG at 24 h and overall Δ-TG became insignificant, while other results were unaffected. CONCLUSION: Our findings support the general use of IT for inpatient management of HTG-AP, restricting BPT to those predicted or found to respond poorly to IT.

Optimising fluid requirements after initial resuscitation: A pilot study evaluating mini-fluid challenge and passive leg raising test in patients with predicted severe acute pancreatitis.

BACKGROUND: The goals and approaches to fluid therapy vary through different stages of resuscitation. This pilot study was designed to test the safety and feasibility of a fluid therapy protocol for the second or optimisation stage of resuscitation in patients with predicted severe acute pancreatitis (SAP). METHODS: Spontaneously breathing patients with predicted SAP were admitted after initial resuscitation and studied over a 24-h period in a tertiary hospital ward. Objective clinical assessment (OCA; heart rate, mean arterial pressure, urine output, and haematocrit) was done at 0, 4, 8, 12, 18-20, and 24 h. All patients had mini-fluid challenge (MFC; 250 ml intravenous normal saline within 10 min) at 0 h and repeated at 4 and 8 h if OCA score ≥2. Patients who were fluid responsive (>10% change in stroke volume after MFC) received 5-10 ml/kg/h, otherwise 1-3 ml/kg/h until the next time point. Passive leg raising test (PLRT) was done at each time point and compared with OCA for assessing volume status and predicting fluid responsiveness. RESULTS: This fluid therapy protocol based on OCA, MFC, and PLRT and designed for the second stage of resuscitation was safe and feasible in spontaneously breathing predicted SAP patients. The PLRT was superior to OCA (at 0 and 8 h) for predicting fluid responsiveness and guiding fluid therapy. CONCLUSIONS: This pilot study found that a protocol for intravenous fluid therapy specifically for the second stage of resuscitation in patients with predicted SAP was safe, feasible, and warrants further investigation.

Randomized controlled trial: neostigmine for intra-abdominal hypertension in acute pancreatitis.

BACKGROUND: Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP. METHODS: In this single-center, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 h. Patients with sustained intra-abdominal pressure (IAP) ≥ 12 mmHg were randomized to receive intramuscular neostigmine (1 mg every 12 h increased to every 8 h or every 6 h, depending on response) or continue conventional treatment for 7 days. The primary outcome was the percent change of IAP at 24 h after randomization. RESULTS: A total of 80 patients were recruited to neostigmine (n = 40) or conventional treatment (n = 40). There was no significant difference in baseline parameters. The rate of decrease in IAP was significantly faster in the neostigmine group compared to the conventional group by 24 h (median with 25th-75th percentile: -18.7% [- 28.4 to - 4.7%] vs. - 5.4% [- 18.0% to 0], P = 0.017). This effect was more pronounced in patients with baseline IAP ≥ 15 mmHg (P = 0.018). Per-protocol analysis confirmed these results (P = 0.03). Stool volume was consistently higher in the neostigmine group during the 7-day observational period (all P < 0.05). Other secondary outcomes were not significantly different between neostigmine and conventional treatment groups. CONCLUSION: Neostigmine reduced IAP and promoted defecation in patients with AP and IAH. These results warrant a larger, placebo-controlled, double-blind phase III trial. Trial registration Clinical Trial No: NCT02543658 (registered August /27, 2015).

Stress Hyperglycemia Is Independently Associated with Persistent Organ Failure in Acute Pancreatitis.

BACKGROUND/AIMS: Stress hyperglycemia is common in critical illness but it has not been clearly studied in patients with acute pancreatitis (AP). This study aimed to investigate the specific blood glucose (BG) level that defines stress hyperglycemia and to determine the impact of stress hyperglycemia on clinical outcomes in AP patients. METHODS: AP patients admitted ≤ 48 h after abdominal pain onset were retrospectively analyzed. Patients were stratified by pre-existing diabetes and stress hyperglycemia was defined using stratified BG levels for non-diabetes and diabetes with clinical outcomes compared. RESULTS: There were 967 non-diabetic and 114 diabetic (10.5%) patients met the inclusion criteria and the clinical outcomes between these two groups were not significantly different. In non-diabetes, the cut-off BG level of ≥ 180 mg/dl was selected to define stress hyperglycemia with an 8.8-fold higher odds ratio for persistent organ failure (POF) (95% CI 5.4-14.3; P < 0.001). For diabetes, ≥ 300 mg/dl was selected with a 7.5-fold higher odds ratio for POF (95% CI 1.7-34.3; P = 0.009). In multivariable logistic regression, stress hyperglycemia was independently associated with POF, acute necrotic collection, major infection and mortality. The combination of BG and systemic inflammatory response syndrome (SIRS) score in predicting POF was better than SIRS or Glasgow score alone. CONCLUSIONS: This study identifies a cut-off BG level of ≥ 180 mg/dl and ≥ 300 mg/dl was optimal to define stress hyperglycemia for non-diabetic and diabetic AP patients, respectively. There was a significant relationship between stress hyperglycemia and adverse clinical outcomes.