Cardiac Surgery Recovery, Complex Cardiovascular Surgery With Cardiopulmonary Bypass, Cytokine Storm, Inflammation, Pediatric Open Heart Surgery
Conditions
Keywords
Feasibility pilot study, Pediatric open heart surgery, Hemoadsorption
Brief summary
This prospective single-center randomized controlled trial aims at evaluating the safety and feasibility of an hemoadsorption protocol using Jafron HA-60 during cardio-pulmonary bypass in 20 pediatric patients undergoing open-heart surgery.
Detailed description
Cardiopulmonary bypass (CPB) is an extracorporeal system that temporarily takes over the functions of the heart and lungs by diverting blood during cardiac surgery. However, the use of CPB is know to trigger a significant systemic inflammatory response, largely mediated by cytokines. In severe cases, this response may result in vasoplegia, hypotension, and subsequent organ dysfunction. Several pharmacological interventions have been investigated to reduce the incidence and severity of this post-surgical inflammatory response, but results have been very mitagated. Among emerging strategies, the pre-procedural removal of circulating cytokines through hemoadsorption represents a promising approach. In particular the use of a HA-60® cartridge (Jafron Biomedical, Guangdong, China) integrated into the CPB circuit may help attenuate the inflammatory cascade. This pilot study is designed to evaluate the feasibility and safety of implementing an hemoadsorption protocol during cardiopulmonary bypass in a pediatric population. Pediatric patients scheduled for complex cardiac procedures will be enrolled before surgery and randomly assigned in a 1:1 ratio to either receive hemoadsorption therapy with standard care (intervention group) or standard care alone (control group). In the intervention group, an HA-60® hemoadsorption cartridge will be integrated into the CPB circuit during setup and used throughout the duration of the bypass. Four blood samples will be collected : Post-anestesia induction, CPB termination, ICU admission, and 24 hours post ICU admission-to measure cytokine levels. Clinical data, including vital signs, organ support, demographics, and medical history, will be recorded in the electronic medical records.
Interventions
DEVICEHemoadsorption
The hemoadsorption treatment will be performed during the entire duration of the CPB. The blood flow within the hemoadsorber will be controlled and set to 7% of the theoretical minimal CPB flow which is calculated as 2.5 L/min/1.73m2 of body surface area.
Sponsors
Centre Hospitalier Universitaire Vaudois
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 10 Years
Healthy volunteers
No
Inclusion criteria
* Children ≤ 10 years old at study inclusion * Children weighing at least 5 kg at study inclusion * Planned for open-heart cardiac surgery with CPB-time ≥ 120 min and aortic clamping. * Informed consent obtained from parent(s)/legal representative
Exclusion criteria
* Children having an indication to receive hemoadsorption during CPB for drugs removal or other medically justified reason * Previous enrolment into the current study * Off-pump procedure * Chronic immunosuppression (chronic corticosteroid therapy, chemotherapy, anti-leucocyte drugs, TNF blockers or else) * Known allergy to heparin or heparin induced thrombocytopenia. * Severe thrombopenia (platelets count before surgery \< 20G/L) * Parent(s)/legal representative not able to understand/read French and/or English * Participation in another conflicting research study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Screened-to-enrolled patients' ratio and number of intervention delivery group | Start CPB, End CPB, 1 Day and aftrer 28 day | * Screened-to-enrolled patients' ratio ≥ 0.3\* * ≥ 80% of intervention delivery in intervention group (number of patients who received hemoadsorption \> 50% of CPB duration) * Duration of recruitment: no more than 36 months (approximately 0.56 patient per month) * \<5% of study interruptions attribuable to insufficiant resources or logistical constraints \*(Previous pilot studies in intervention contexts report screened-to-enrolled patient ratios of approximately 0.30-0.50; therefore a threshold of ≥ 0.30 has been chosen as a minimal acceptable benchmark for feasibility.) |
| Device-related adverse events | From beginning of cardiopulmonary bypass to 7 days after ICU admission or ICU discharge wichever occurs first. | Assessed with the occurrence of 4 categories of adverse events in each group: Device-related complications: • Technical failure to perform the treatment: thrombosis of the cartridge, circuit leak or inability to perform the treatment for all CPB duration. Tolerance: * New allergic or anaphylactoid reaction (stage ≥ 2 by H. L. Mueller \[5\]) * New fever (\> 39°C for more than an hour). Bleeding/haematological complications\*: * Intracranial haemorrhages * Need for massive transfusion (\>10mL/kg/h during more than 3 consecutive hours) * Incidence of new thrombocytopenia (mild \<150 G/L, moderate, \<100 G/L severe \< 50 G/L) \*(We will consider separately bleeding/haematological complications occurring during the procedure (from CPB initiation to ICU admission) and those occurring from ICU admission to day 7 or ICU discharge, whichever occurs first.) All other event judged relevant by the investigator (i.e. cardiac arrest). NB: "New" means not present at the time of CPB initiation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score at 24 hours | Measured between post-anestesia induction and 24 hours post ICU-admission | Difference in the PELOD-2 score between before surgery and 24 hours after admission to intensive care. The PELOD-2 score ranges from a minimum of 0 (indicating no organ dysfunction) to a maximum of 33 (indicating the most severe level of organ dysfunction) |
| Pediatric Logistic Organ Dysfunction-2 (PELOD-2) worst value | Within 4 hours of ICU admission | Efficacy measured by the PELOD-2 worst value between admission to intensive care and 24 hours after admission to intensive care. The PELOD-2 score ranges from a minimum of 0 (indicating no organ dysfunction) to a maximum of 33 (indicating the most severe level of organ dysfunction) |
| Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score at 48 hours | Measured between 24 hours and 48 hours after ICU admission | PELOD-2 difference between groups in the PELOD-2 score measured between 24 hours and 48 hours after ICU admission. The higher the PELOD-2 the highest the probability of death.The PELOD-2 score ranges from a minimum of 0 (indicating no organ dysfunction) to a maximum of 33 (indicating the most severe level of organ dysfunction). |
| Change in cytokine levels compared to baseline | at the end of CPB, at the admission in ICU and 24 hours after ICU admission | Relative and absolute change in the plasma levels of cytokines at different timepoints, compared with their levels at baseline (post-anestesia induction). |
| ICU and hospital lenght of stay | At time of hospital discharge, an average 20 days after ICU admission | Lengths of stays, in days |
| ICU, hospital, and 28 days (from ICU admission) mortality | At time of hospital discharge, an average 20 days after ICU admission and up to 28 days after ICU admission | All-cause mortality |
| Days alive without respiratory support | At day 28 from ICU admission | Number of days alive and without mechanical ventilation |
| Days alive without renal replacement therapy | At day 28 from ICU admission] | Number of days alive and without renal replacement therapy |
| Days alive without vasopressors | At day 28 from ICU admission] | Number of days alive and without vasopressors |
| Days alive without ECMO support | At day 28 from ICU admission | Number of days alive and without Extracorporeal membrane oxygenation (ECMO) |
| Post-operative complications | At time of ICU discharge, up to 7 days after ICU admission | Post-operative Acute Kidney Injury, transfusion of red blood cells, sepsis, liver injury |
Countries
Switzerland
Contacts
CONTACTIsabelle Cristiani
CONTACTAntoine Schneider, MD-PhD
PRINCIPAL_INVESTIGATORAntoine Schneider, MD-PhD
Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne
Outcome results
None listed