Circuit oxygenator contributes to extracorporeal membrane oxygenation-induced hemolysis

Abstract

Hemolysis can occur as a consequence of extracorporeal membrane oxygenation (ECMO) and is associated with increased mortality and morbidity. Shear stress generated by flow through the circuit and oxygenator is believed to cause ECMO-induced hemolysis. We hypothesize that either a smaller dimension oxygenator or an in-line hemofilter will increase ECMO-associated hemolysis. Circuits were configured with a Quadrox-D Adult oxygenator (surface area 1.8 m), Quadrox-iD Pediatric oxygenator (surface area 0.8 m), or Quadrox-D Adult oxygenator with an in-line hemofilter (N = 4) and ran for 6 hours. Samples were collected hourly from the ECMO circuit and a time-based hemolysis control. Plasma hemoglobin levels were assayed. Circuit-induced hemolysis at each time point was defined as the change in plasma hemoglobin standardized to the time-based hemolysis control. Plasma hemoglobin increased with the use of the smaller dimension pediatric oxygenator as compared with the adult oxygenator when controlling for ECMO run time (p = 0.02). Furthermore, there was a greater pressure gradient with the smaller dimension pediatric oxygenator (p < 0.05). Plasma hemoglobin did not change with the addition of the in-line hemofilter. The use of a smaller dimension pediatric oxygenator resulted in greater hemolysis and a higher pressure gradient. This may indicate that the increased shear forces augment ECMO-induced hemolysis.

Figure 1. Circuit Design

Circuits were built on a Sorin Slll pump console equipped with a Sorin Centrifugal Pump (SCP) system (Sorin Group, Denver, CO, USA) to replicate typical clinical practice and were configured with a:

1. Quadrox-iD Adult oxygenator: Configured using 3/8″ diameter SMART coated tubing connections. Direct connections were made to the 3/8″ blood inlet and outlet for the adult oxygenator.

2. Quadrox-iD Pediatric oxygenator: Configured using 3/8″ diameter SMART coated tubing connections. There was a step down and step up connection made for the 1/4″ blood inlet and outlet for the pediatric oxygenator.

3. Quadrox-iD Adult oxygenator with an in-line hemofilter: Configured using 3/8″ diameter SMART coated tubing connections. There was a step down and step up connection made for the 3/16″ blood inlet and outlet for the hemofilter.

A 500mL reservoir bag was used to simulate the patient. Arrows depict direction of flow.

Figure 2. Study Design Sampling

Blood was circulated through the circuit configurations for six hours. Samples were collected hourly from the circuit and time based hemolysis control, which consisted of a sample from the circuit prime maintained in a water bath set at 36°C. 50 ml of filtrate was removed from the hemofiltered circuits at hour 2 and 4.

Figure 3A. Use of a smaller dimension pediatric oxygenator was associated with a greater increase in plasma hemoglobin

Plasma samples were obtained hourly from both the ECMO circuit and the time based hemolysis control that was maintained at 36°C. Hemoglobin was measured by a Quantichrom assay kit (BioAssay Systems). Hemolysis attributed to the ECMO circuit was defined as the change in pHb at each hour standardizing to pHb measured in time based hemolysis control. Median values (25^th, 75^th percentile) are displayed. N=4.

Figure 3B. Plasma hemoglobin levels were not significantly increased with the use of the hemofilter when controlled for ECMO run time

Plasma samples were obtained hourly from the adult circuit in the presence and absence of the hemofilter. Hemoglobin values were measured and standardized to the time based hemolysis control hemoglobin values. Median values (25^th, 75^th percentile) are displayed. N=4.