Reduction in Blood Product Transfusion Requirements with Early On-ECMO Repair of Congenital Diaphragmatic Hernia

Stats

• One in every 2,500 babies born has congenital diaphragmatic hernia (CDH)
• 54 patients analyzed in study
• 30% babies born with CDH require extracorporeal membrane oxygenation (ECMO) support

Background

About 30% of infants born with a CDH require ECMO support.

Survival among infants placed on ECMO has remained around 50%; Its use is associated with more severe CDH and increased risk of morbidity and mortality.

Patients who undergo CDH repair while on ECMO have an increased risk for perioperative bleeding. Repair after ECMO is preferred but for high-risk patients, repair must occur on ECMO for the best chance of successful repair and to provide more time for lung growth.

For those requiring repair while on ECMO, previous medical literature is contradictory, with some studies suggesting benefits to early repair while others suggest improved survival when repair is delayed until after ECMO decannulation.

The literature does clearly outline that late salvage repair when a patient is unable to wean off ECMO is associated with the worst outcomes. Optimizing ECMO repair is an important ongoing discussion.

Researchers in the Colorado Fetal Care Center at Children’s Hospital Colorado hypothesized that early repair on ECMO (defined as within 48 hours of ECMO cannulation) compared to later repair on ECMO would:

• Be associated with decreased transfusion requirements
• Have better survival outcomes

Methods: retrospective review

The study included all patients at Children’s Colorado who were placed on ECMO prior to CDH repair. Characteristics and outcomes were compared to patients repaired on ECMO and off ECMO. “Early repair” was considered to occur within 48 hours of ECMO initiation. “Late repair” was considered to occur after 48 hours of  ECMO cannulation.

CDH management and decision for ECMO initiation

At Children’s Colorado, CDH care is multidisciplinary and includes neonatologists, pediatric surgeons, maternal fetal medicine specialists, cardiologists and radiologists.

• Prenatal evaluation includes fetal ultrasound and MRI at 24 weeks and 34 weeks gestational age; the study used 34-week MRI data.
• Dedicated CDH delivery team includes a neonatal team lead for all deliveries, two neonatal attendings, a nurse practitioner, a neonatal nursing team and an ICU pharmacist.
• Resuscitation is standardized and coordinated to initial stabilization by a dedicated team consistently for every CDH resuscitation.
• Surgical repair is at surgeon’s discretion.

Anticoagulation and blood product management for patients on ECMO

Heparin is the primary anticoagulation used for patients maintained on ECMO utilizing a standardized titration algorithm and monitoring of anti-Xa levels (target level is 0.2 to 0.5).

• Perioperative ECMO anticoagulation algorithm is implemented 4 hours before surgery (heparin held, amicar given one hour before incision)
• During surgery, heparin held, amicar infused at 30 mg/kg/h
• Amicar given for 24 hours after surgery, restarted if thromboelastography (TEG) suggests clot lysis
• Heparin restarted 6 hours after surgery, titrated utilizing a standardized heparin titration algorithm and monitoring of anti-Xa levels (target level 0.2 to 0.4)
• 24 to 48 hours after surgery heparin adjusted to moderate risk protocol (target level 0.3 to 0.5)
• On post-operative day 2, heparin is adjusted to low-risk protocol (target level 0.4 to 0.7) if no signs of active bleeding

Transfusions are guided by the following parameters:

• PT > 18, platelets < 80, fibrinogen < 120
• TEG is used to guide amicar if clot lysis is suggested by study

Results

Repair off ECMO vs. repair on ECMO

Patients with an intrathoracic liver

• 33% repaired off ECMO
• 95.8% repaired on ECMO

Median percent predicted lung volumes (PPLV) on MRI

• 21.7% repaired off ECMO
• 14.3% repaired on ECMO

Bleeding complications

• No statistical difference among cohorts
• Significantly less blood product usage with lower PRBC, FFP and platelet transfusion requirements in off ECMO repair

Early repair on ECMO vs. late repair on ECMO

• Prenatal diagnosis is significantly more common in early repair group
  • Correlated with more C-section deliveries
• Most patients cannulated within first 24 hours of life
• Both groups similar in all markets of prenatal risk factors

Primary Outcomes

Bleeding complications

• No significant difference in number of patients needing surgical intervention for bleeding
• Significantly lower PRBC and platelet transfusion associated with early ECMO repair
  • Median 72.0 mL/kg PRBV and 75.0 mL/kg platelets for early repair
  • Median 151.9 mL/kg PRBV and 98.7 mL/kg platelets for late repair

Secondary Outcomes

• Early repair associated with fewer days on mechanical ventilation and shorter length of stay
• Early repair had significantly higher neonatal period survival rate
  • 84.6% vs. 54.5% of late repair

Discussion and conclusion: Early repair is associated with improved outcomes, less bleeding and decreased blood product requirement postoperatively

Patients repaired on ECMO:

• Early repair associated with significantly lower postoperative blood product usage, specifically reduced transfusion of platelets and PRBCs
• Typically, O/E LHR <35%

Patients repaired off ECMO:

• Significantly lower perioperative transfusion requirements, most requiring no postoperative transfusions
• Improved survival to discharge (83% compared to 50% repaired on ECMO)
• Shorter ECMO duration (7 median days vs. 12.5 days when repaired on ECMO)
• Significantly higher median PPLV on MRI; were more likely to have an intra-abdominal liver

Study data and current evidence suggest benefits with early repair for patients who undergo surgery on ECMO. Early repair:

• May reduce overall duration of ECMO use (12-day median ECMO duration vs. 14-day median)
• Trended toward lower duration of mechanical ventilation and length of stay
• 16.8% greater survival to discharge
• 34.6% bleeding complications compared to 54.5%
  • Associated with significant differences in PBRC and platelet transfusion requirements
• Could reduce costs and transfusion risks

To the knowledge of study authors, this is the first study to evaluate the association of surgical timing on ECMO with perioperative blood product usage, which could help improve utilization of resources.