Continuous renal replacement therapy and therapeutic plasma exchange in pediatric liver failure.

Patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) have significant morbidity and mortality. They require extracorporeal blood purification modalities like continuous renal replacement therapy (CRRT) and therapeutic plasma exchange (TPE) as a bridge to recovery or liver transplantation. Limited data are available on the outcomes of patients treated with these therapies. This is a retrospective single-center study of 23 patients from 2015 to 2022 with ALF/ACLF who underwent CRRT and TPE. We aimed to describe the clinical characteristics and outcomes of these patients. Median (IQR) age was 0.93 years (0.57, 9.88), range 16 days to 20 years. Ten (43%) had ALF and 13 (57%) ACLF. Most (n = 19, 82%) started CRRT for hyperammonemia and/or hepatic encephalopathy and all received TPE for refractory coagulopathy. CRRT was started at a median of 2 days from ICU admission, and TPE started on the same day in most. The liver transplant was done in 17 (74%), and 2 recovered native liver function. Four patients, all with ACLF, died prior to ICU discharge without a liver transplant. The median peak ammonia pre-CRRT was 131 µmol/L for the whole cohort. The mean (SD) drop in ammonia after 48 h of CRRT was 95.45 (43.72) µmol/L in those who survived and 69.50 (21.70) µmol/L in those who did not (p 0.26). Those who survived had 0 median co-morbidities compared to 2.5 in non-survivors (aOR (95% CI) for mortality risk of 2.5 (1.1-5.7), p 0.028). Conclusion: In this cohort of 23 pediatric patients with ALF or ACLF who received CRRT and TPE, 83% survived with a liver transplant or recovered with their native liver. Survival was worse in those who had ACLF and those with co-morbid conditions. What is Known: •  Pediatric acute liver failure is associated with high mortality. •  Patients may require extracorporeal liver assist therapies (like CRRT, TPE, MARS, SPAD) to bridge them over to a transplant or recovery of native liver function. What is New: • Standard volume plasma exhange has not been evaluated against high volume plasma exchange for ALF. • The role, dose, and duration of therapeutic plasma exchange in patients with acute on chronic liver failure is not well described.

Therapeutic plasma exchange for mechanical red cell hemolysis: A case series.

We present three cases of severely elevated plasma free hemoglobin (PFH) in pediatric patients on mechanical circulatory support devices at a tertiary pediatric care center. Due to severe levels of PFH in the setting of critical illness with the inability to pursue immediate mechanical device exchange, membrane filtration therapeutic plasma exchange (TPE) was performed, which resulted in a lowering of PFH levels. However, long-term outcomes were heterogeneous across the cases. This case series reviews patient presentation, organ function before and after TPE, and the overall role of TPE as an effective treatment option to decrease severely elevated PFH levels. In doing so, we hope to add to what is known about the use of TPE for mechanical red cell hemolysis and provide guidance on its use in critically ill patients.

Characteristics of pediatric non-cardiac eCPR programs in United States and Canadian hospitals: A cross-sectional survey.

OBJECTIVE: To characterize practices surrounding pediatric eCPR in the U.S. and Canada. METHODS: Cross-sectional survey of U.S. and Canadian hospitals with non-cardiac eCPR programs. Variables included hospital and surgical group demographics, eCPR inclusion/exclusion criteria, cannulation approaches, and outcomes (survival to decannulation and survival to discharge). RESULTS: Surveys were completed by 40 hospitals in the United States (37) and Canada (3) among an estimated 49 programs (82% response rate). Respondents tended to work in >200 bed free-standing children's hospitals (27, 68%). Pediatric general surgeons respond to activations in 32 (80%) cases, with a median group size of 7 (IQR 5,9.5); 8 (20%) responding institutions take in-house call and 63% have a formal back-up system for eCPR. Dedicated simulation programs were reported by 22 (55%) respondents. Annual eCPR activations average approximately 6/year; approximately 39% of patients survived to decannulation, with 35% surviving to discharge. Cannulations occurred in a variety of settings and were mostly done through the neck at the purview of cannulating surgeon/proceduralist. Exclusion criteria used by hospitals included pre-hospital arrest (21, 53%), COVID+ (5, 13%), prolonged CPR (18, 45%), lethal chromosomal anomalies (15, 38%) and terminal underlying disease (14, 35%). CONCLUSIONS: While there are some similarities regarding inclusion/exclusion criteria, cannulation location and modality and follow-up in pediatric eCPR, these are not standard across multiple institutions. Survival to discharge after eCPR is modest but data on cost and long-term neurologic sequela are lacking. Codification of indications and surgical approaches may help clarify the utility and success of eCPR.

Similar frequency of atrial perforation between atrial and bicaval dual lumen veno-venous ECMO cannulas in a pediatric population.

PURPOSE: Complications associated with use of dual-lumen venovenous extracorporeal membrane oxygenation (VV-ECMO) cannulas are of concern in pediatric patients. While the risk of atrial perforation is believed to be higher with bicaval cannulas, direct comparison of complication rate between atrial and bicaval cannulas has not been conducted in this population. METHODS: A retrospective review was conducted at a free-standing children's hospital of all patients 0-18 years old, placed on VV-ECMO with a dual-lumen cannula from January 2009 to December 2018. Patients were grouped based on cannula type. Complications were assessed over the entire duration of the ECMO run. Logistic regression analyses were used to evaluate for an association between cannula type and risk of pericardial effusion or cannula-related complication requiring median sternotomy or pericardial drain placement. RESULTS: During the study period 119 patients were placed on VVECMO using a dual-lumen cannula. Eighty-two patients (69%) were <2 years old, 19 (16%) were 2-10 years old, and 18 (15%) were 11-18 years old. Seventy-three were cannulated with an atrial cannula and 46 patients received a bicaval cannula. Pericardial effusions were seen in 30% and 24% of these patients respectively while severe complications were seen in 9.6% and 8.7% of patients respectively. Compared to patients treated with a bicaval cannula, those who received an atrial cannula had similar odds of effusions (OR: 1.41, 95% CI: 0.62-3.36) and severe complications (OR 0.89, 95% CI: 0.27-3.18). After adjusting for age, weight, cannula and circuit manipulations, and use of echocardiography, the OR of effusion was 1.91 (95% CI: 0.65-6.42), and the adjusted OR of severe complication was 0.69 (95% CI: 0.16-3.33). CONCLUSIONS: There were no significant differences in frequency of pericardial effusions or severe cannula-related complications between the treatment groups across all pediatric patients and within the subgroup of patients under 2 years of age.

Conversion From Activated Clotting Time to Anti-Xa Heparin Activity Assay for Heparin Monitoring During Extracorporeal Membrane Oxygenation.

OBJECTIVES: Anticoagulation with unfractionated heparin remains the most common therapy used to prevent circuit thrombosis during extracorporeal membrane oxygenation, but no consensus exists on the optimal method or targets for heparin monitoring. From 2015 to 2018, we switched from monitoring heparin during extracorporeal membrane oxygenation using activated clotting times to anti-Xa heparin activity assays. This study describes the transition from activated clotting time to anti-Xa heparin activity assay monitoring and the associated clinical changes. DESIGN: Retrospective analysis at single institution. SETTING: Referral Children's Hospital. PATIENTS: A total of 145 pediatric patients over 152 extracorporeal membrane oxygenation runs using 206 extracorporeal membrane oxygenation circuits. INTERVENTIONS: Anticoagulation protocol quality improvement. MEASUREMENTS AND MAIN RESULTS: From 2015 to 2018, heparin monitoring during extracorporeal membrane oxygenation changed from hourly activated clotting time to anti-Xa heparin activity assay every 6 hours with an associated 75% reduction in the circuit changes per extracorporeal membrane oxygenation day. Over the 4 years, patients with an average anti-Xa heparin activity assay of at least 0.25 U/mL showed a 59% reduction in circuit changes per extracorporeal membrane oxygenation day compared with less than 0.15 U/mL. In addition to its association with reduced circuit changes, anti-Xa heparin activity assay monitoring was also associated with reduced heparin dose changes per day from 11 ± 4 to 2 ± 1 (p < 0.001), smaller heparin dose changes (less variation in dose), and reduced diagnostic phlebotomy volumes from 41 ± 6 to 25 ± 11 mL/day (p < 0.001). The number of patients with reported bleeding decreased from 69% using activated clotting time to 51% (p = 0.03). Transfusion rates did not change. CONCLUSIONS: Over 4 years, we replaced the activated clotting time assay with the anti-Xa heparin activity assay for heparin monitoring during extracorporeal membrane oxygenation. Minimum anti-Xa heparin activity assay levels of 0.25 U/mL were associated with reduced circuit changes. Further studies are needed to determine the optimum anti-Xa heparin activity assay therapeutic range during extracorporeal membrane oxygenation.

Monitoring Hemostasis During Extracorporeal Life Support.

To balance the risk of bleeding versus circuit thrombosis during extracorporeal life support (ECLS), it is important to monitor anticoagulants and hemostasis. We evaluated the prothrombin time (PT), partial thromboplastin time (PTT), activated clotting time (ACT), and antifactor Xa heparin activity (aXa) correlation with changes in coagulation factor and heparin levels using in vitro and in vivo samples. aXa correlated with heparin (r = 0.97) and antithrombin (r = 0.98) but was unaffected by other parameters. PT correlated with coagulation factors (r = 0.88) but was minimally affected by heparin or other parameters. When single parameters were changed, ACT was insensitive to <0.5 U/ml heparin, correlated with coagulation factors (r = 0.99), and was affected by factor XII and platelets. When multiple parameters changed in vitro and in vivo, ACT was not correlated with heparin or coagulation factors. PTT correlated with heparin and coagulation factors individually but had low correlation when multiple parameters changed in vitro and in vivo. In conclusion, aXa is the most specific for heparin levels, and PT is most specific for coagulation factor levels making these assays well suited to monitor anticoagulation and hemostasis for patients on ECLS. PTT is highly variable when multiple parameters are changing in vitro and in vivo, but may be useful when aXa cannot be used because of interference. ACT is too insensitive to heparin, sensitive to too many other factors, and too imprecise to be useful for monitoring hemostasis during ECLS.

Therapeutic Plasma Exchange in Neonatal Septic Shock: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to examine the use of therapeutic plasma exchange (TPE) as adjunctive therapy in neonatal septic shock. STUDY DESIGN: This retrospective cohort study was performed on a convenience sample of neonates in a quaternary children's hospital between January 2018 and February 2019. RESULTS: We identified three neonates with septic shock who received TPE. Two neonates had adenovirus sepsis, and one had group B streptococcal sepsis. All neonates were on extracorporeal life support (ECLS) when TPE was started. The median duration of TPE was 6 days (interquartile range [IQR]: 3-15), with a median of four cycles (IQR: 3-5). Lactate levels decreased significantly after TPE (median before TPE: 5.4 mmol/L [IQR: 2.4-6.1] vs. median after TPE: 1.2 mmol/L [IQR: 1.0-5.8]; p < 0.001). Platelet levels did not change (median before TPE: 73,000/mm3 [IQR: 49,000-100,000] vs. median after TPE: 80,000/mm3 (IQR: 62,000-108,000); p = 0.2). Organ failure indices improved after TPE in two of the three neonates. Hypocalcemia was seen in all cases despite prophylactic calcium infusions. One neonate died, and two survived to ICU discharge. CONCLUSION: TPE can be safely performed in neonates with septic shock. TPE may have a role as an adjunctive therapy in neonates with septic shock requiring ECLS.

Impacts of a Pediatric Extracorporeal Cardiopulmonary Resuscitation (ECPR) Simulation Training Program.

OBJECTIVE: To examine the impacts of a large-scale simulation-based extracorporeal cardiopulmonary resuscitation (ECPR) training program in an academic children's hospital. METHODS: The study followed a quasi-experimental, mixed-method, time series design. Two-hour high-fidelity ECPR simulations were held monthly in the pediatric, cardiac, and neonatal intensive care units. Intensive care unit-specific cases were used in each unit. The learning objectives for all cases were the same. Each simulation included an average of 11 health care professionals, including nurses, physicians, respiratory therapist, and perfusionists. Impacts of training were examined using Kirkpatrick's 4-level model: reactions, learning, behaviors, and results. Participant surveys, semistructured interviews, facilitator observations, applied cognitive task analysis, and hospital code data were used to examine the impacts of training. RESULTS: From February 2014 to October 2016, a total of 332 health care professionals participated in 29 ECPR simulations. Participants enjoyed the simulations and reported learning gains. Applied cognitive task analysis revealed 2 specific behaviors, coordination of compressions with surgical cannulation and performing sterile compressions, that were targeted for further training. The rate of adherence to the ECPR activation protocol improved from 83% (48/58) before simulations started to 95% (92/97) after simulations (P = .02). ECPR activation time decreased from 7 minutes (interquartile range, 4-9 minutes) before simulations started to 2 minutes (interquartile range, 1-4 minutes) after simulations (P < .01). CONCLUSIONS: Large-scale simulation-based ECPR training was associated with positive reactions, learning gains, behavioral change, improved adherence to the ECPR activation protocols, and faster activation times. Other children's hospital that perform ECPR should consider simulation-based training.