Why Do We Wash The Blood Prime in the ECMO Pump? Nobody Else Does!
The initiation of CPB or ECMO results in the rapid exchange of blood at the rate of 100 ml/kg/min in infants. Cardiac arrest from the rapid infusion of PRBC is a well known complication of blood transfusions. Other electrolyte imbalances can cause cardiac arrhythmias and ventricular over distention. Brain damage and increased mortality from hypernatremia in children is also well documented. The transfusion of PRBC stored in preservatives is not recommended in amounts greater than 15 mL/kg/dose in infants because of the potential adverse effects that these preservatives can have. Yet annually 50,000 children undergo CPB and 3,000 undergo ECMO by being placed on pumps that contain hyperkalemic, hypernatremic and hyperosmotic primes with AS-1 or AS-3 preserved PRBC at the exchange rate of 100 ml/kg/min in infants. Some of the many complications of CPB and ECMO probably are masked by the assumption that they are caused by an unavoidable systemic inflammatory response or unfortunate anticoagulation side-effects rather than by an iatrogenic process that can be mitigated by washing the blood prime.
Virtually no research has been done since 1953 to determine if an unwashed blood prime is safe. Drs. Naomi Luban, Ronald Strauss and Heather Hume (nationally known experts on pediatric blood transfusions) in 1991 and again in 2003 recommended avoiding the use of entire units of PRBC in extended-storage media in massive exchange transfusion, cardiac surgery, and extracorporeal membrane oxygenation in children (1). Under these circumstances they recommended that the preservative medium should be removed and the PRBC re-suspended in an appropriate fluid. In other words the prime should be washed. Their recommendations were “based on calculations and hypothetical settings, not actual data. Accordingly, they are tentative and should be altered as definitive information becomes available.”
Back in the late 1980’s we would prime our pumps, both the cardiopulmonary bypass (CPB) pump and the ECMO pump with a unit of whole blood (WB) and a unit of packed red blood cells. The issue frequently seen at that time was a greatly elevated glucose of the blood prime; frequently higher than a glucometer could measure. This was not good for the patients, particularly the infant and small child. So in the early 1990s, after hemoconcentrators became available, we began ‘washing’ the blood prime in our CPB pumps. We would simply add additional crystalloid fluid to the prime and then remove it by ultrafiltration, diluting the glucose to an acceptable level. This was easy to do on a CPB pump, but we didn’t know how to do it on the ECMO pump prime. So for years the ECMO patients were often subjected to greatly elevated glucose values the first day or two of ECMO.
During the time frame of 1987 to 1995, the types of blood products given to us to prime our pumps changed. First, WB no longer became available, only citrated PRBC and fresh frozen plasma (FFP). Then by 1995 mostly AS-1 PRBC and FFP were available. As the blood products changed so did the amount of acid in the PRBC. WB retains much of it natural buffers. So to adjust its pH to a compatible 7.4, only a small amount of NaHCO3 needs to be added. When the plasma is drawn off to make citrated PRBC, most of the natural buffers are removed and the acid builds up in the PRBC. This requires the addition of larger amounts of NaHCO3 to normalize the pH. With AS-1 PRBC any residual natural buffers are totally removed and the acid needs lots of NaHCO3 to be normalized.
Beginning in the mid-1990s we began to notice more frequent complications of edema and renal insufficiency in the post-CPB patients. By 2005 the situation had become intolerable with the surgeon becoming quite vociferous with his complaints about post-op edema and renal dysfunction. While we were doing a good job of controlling elevated glucose values the sodium and osmolarity of the CPB pump prime were well above the normal range. See the graphs below. From 1999 through 2005 the sodium of our CPB blood prime rose from 155 mEq/L to almost 180 mEq/L (normal = 135-145). As the sodium increased the calculated osmolarity also increased from about 325 mosmols/L to 370 mosmols/L (normal = 270-300). See the graphs below.
We were seeing changes in our ECMO patients as well. Prior to Nov of 1995 (ECMO patients 1-188), only 9% had systemic hypertension requiring treatment and the brain infarction rate was 10%. After Nov. 1995 through Sep. 2005 (ECMO patients 189-393), 54% had systemic hypertension and 18% had brain infarcts. See the table below.
At that time a review of the ECMO pump primes and post-ECMO labs of the most recent 19 ECMO patients demonstrated hypernatremia, hyperosmolarity and renal dysfunction. A prime wash process was instituted in an attempt to mitigate these abnormalities in the prime. These last 19 patients with unwashed ECMO blood primes were compared to the succeeding 20 ECMO patients who received a washed ECMO blood prime after prime washing was formally instituted. See the table below.
Both the CPB and ECMO patients were suffering from the need for excessive amounts of NaHCO3 in the prime to normalize the pH. So in 2006 we modified our wash techniques to better control the prime sodium and osmolarity. And, for the first time, we began washing the blood prime of the ECMO pump in a fashion similar to that used for our CPB pump. We were successful in lowering both the sodium and osmolarity. Many of the complications we had been seeing were becoming much less frequent.
So why don’t other people wash their blood primes? Well, some do. About half of the pediatric perfusionists wash their CPB blood primes. The other half thinks that the edema and renal complications are the result of an unavoidable systemic inflammatory response syndrome seemingly associated with extracorporeal support and that washing is just a waste of time. Most ECMO program primers don’t know about the problems caused by hypernatremia and hyperosmolarity, again thinking that these complications are just part of the normal risks of going on ECMO.
When a baby is first placed on ECMO without washing the prime there are outward signs that things are not right. But since the child is covered by sterile drapes during the cannulation surgery and the outward symptoms resolve fairly quickly, nobody notices. But when an ECMO circuit is changed to a new circuit with an unwashed blood prime and the child is no longer hidden by sterile drapes the child can exhibit some startling symptoms. Among the symptoms I have seen are sudden and severe Harlequin sign, vasodilation of the entire skin surface causing the child to turn beet red, seizure-like movements, hemodynamic instability, cardiac arrhythmias and pulmonary hemorrhage. Delayed symptoms include renal dysfunction and brain hemorrhage or infarct.
The ‘Harlequin sign’ in newborns is thought to be a benign and temporary imbalance in the tone of cutaneous blood vessels secondary to hypothalamic immaturity with no known pathologic significance. However, ‘Harlequin syndrome’, which looks very similar, is caused by damage to the autonomic nervous system. This may be a symptom of injury to the central nervous system caused by the sudden infusion of a large amount of unwashed pump blood prime.
Two years ago an out of town ECMO transport team came to take one of our infant ECMO patients to a distant city for further treatment. The perfusionist priming his portable ECMO pump with PRBC infused NaHCO3 in an amount I would consider too high. He also added mannitol which further increased the osmolarity to a level that I would consider dangerous. But he reassured me that he was following their normal prime procedure. Upon transferring to this new ECMO circuit from ours, the infant exhibited the most profound Harlequin sign that I had ever seen; completely beet red on the left side and blanched white on the right side with a precise line of demarcation from the top of his head to his pubis. The peds physician on the transport team was quite alarmed at this. But in my experience this was a common occurrence in infants when exposed to an unwashed ECMO circuit prime. Two days after arriving at the new hospital the child demonstrated a brain hemorrhage and infarct by CT scan. The patient expired. Was this co-incidence or did the unwashed blood pump prime play a part? I think it did. So that’s why we wash the blood in the ECMO prime.