Perfusionists Need To Partner With A New Type Of Physician

The partnership between the perfusionist and the cardiac surgeon goes back to the very beginnings of open heart surgery. Even today, most perfusionists work under the auspices and authority of the heart surgeon or anesthesiologist. The vast majority of perfusion procedures are cardiac surgery related with perfusionists performing hundreds of thousands of cases per year. Most perfusionists are involved in some form of extended applications such as VADs or balloon pumps. Even so, this is still primarily associated with heart surgery. But times are changing fast for perfusion applications.

One morning you may arrive at work and discover that your hospital now has an ECPR/ECMO program. ECPR/ECMO programs will soon become mandatory in critical care hospitals. Like the fire extinguishers in the hospital corridors, ECPR/ECMO is something that must be available, but hopefully never used. You may be a part of it or it may be staffed by RNs and RTs. Either way, there will be a new type of physician in charge of the program. It might be a surgeon, anesthesiologist or an intensivist, but his/her primary emphasis will be on ECPR/ECMO.

I believe that any capable perfusionist can set-up a pump-oxygenator for rapid extracorporeal life support. So, what’s the big deal? In case the reader doesn’t know, rapid deployment is usually unsuccessful. And that’s where the new type of physician is needed.

CPR resuscitation has experienced very little improvement in the last 50 years. Despite the intensive applications epitomized in ACLS and PALS, survival to discharge is still only about 15% ¹. We are now just beginning to understand why critical care personnel have failed to significantly improve CPR resuscitation outcomes over the last half century. In fact, the reason for failure has been staring perfusionists and heart surgeons on the face all that time: reperfusion injury ². We know how to prevent reperfusion injury in the heart during cardiac surgery and restart it successfully without causing other organ damage ³. Comfortable in our caverns of sterility, perfusionists have paid scant attention to the on-going battle of non-cardiac patients outside of the OR where success in restarting the heart after a period of CPR often causes fatal reperfusion injury to the other organ systems and failure to restart the heart always results in the patient’s demise ⁴.

Reperfusion injury is often the culprit in the acute failure of transplanted organs ^{5, 6}. Donor organs are chilled and stored cold for several hours prior to transplantation. Even though the tissues are cold, they are still subject to progressive ischemic hypoxia during storage. Connecting a cold kidney or lung that has been thus stored to the circulation of a warm patient is a prescription for reperfusion injury to occur. Something similar happens to a patient who has a return of spontaneous circulation after a period of CPR or when they are placed on ECPR support.

This new type of physician will be intimately familiar with ECMO, but not just in the sense of knowing how to write orders for a heparin drip or controlling blood flow based on SVO2. This new type of physician will be one who has studied the impact of routine ECMO on patients enduring various types and degrees of shock prior to ECMO. Patients with less severe shock will tolerate ECMO well and go on to recover. Patients with more severe shock will be subjected to the ravages of reperfusion injury, enduring organ damage that will complicate their time on ECMO and possibly result in their death. This new type of physician will take this knowledge gleaned from ECMO patients who are approaching death and apply it to patients who have already died; i.e. CPR resuscitation patients.

ECPR is the emergent form of ECMO ⁷. It is usually a low volume, clear prime pump oxygenator that can be set-up and operated at a moment’s notice and it is used in patients undergoing profound shock requiring CPR. After ten minutes of even the best CPR most patients have developed an extreme intracellular acidosis which literally turns-off the antioxidant enzymes ⁸. The sudden reinstitution of capillary perfusion by the ECPR pump with oxygenated perfuseate often will result in the development of uncontrolled reactive oxygen species which will damage or destroy vital intracellular structures.

This new type of physician (who we can now call a “Reperfusionist”) will have the understanding to know how to prevent the ECPR pump from damaging tissues and instead use the pump in such a way as to prevent reperfusion injury ⁸. It is most likely that this will involve the use of rapidly induced core hypothermia to blunt the adverse chemical reactions of reperfusion injury and the use of hemodilution to combat no-reflow phenomenon caused by capillary damage and white cell aggregation. Even though hypothermia reduces the need for oxygen, the flow rate must be kept high to remove carbon dioxide that has accumulated in the tissues during CPR. This trapped carbon dioxide contributes greatly to the intracellular acidosis ⁹. Furthermore, the hemodilution will allow this high pump flow without pumping excessive oxygen to susceptible tissues.

One additional intervention by the “Reperfusionist” will be to use a drug such as Dantrolene to block the worst of all reperfusion injury mediators; the intracellular flux of calcium. The uncontrolled flux of calcium in the cell causes permanent damage to the mitochondria ¹⁰. Nonetheless, calcium is often given during resuscitation as a cardiac stimulant even though its use is associated with decreased survival and increased brain damage in survivors ¹¹.

On the other hand, patients undergoing CPR as a result of cardiac arrest from hyperkalemia due to malignant hyperthermia or one of its variants often have a high recovery without brain injury even after a sustained resuscitation ^12-15. In these patients, Dantrolene is given to block the hypermetabolic state which includes an uncontrolled intracellular flux of calcium. This may also prevent the calcium mediated mitochondrial damage seen in reperfusion injury. Animal studies have confirmed that Dantrolene has protective effects on hypoxic ischemic tissues ^16-18. One day a drug such as Dantrolene may be given to CPR patients even before epinephrine to control the calcium mediation of reperfusion injury when the heart restarts.

The goal during the first few critical hours of ECPR will be to normalize intracellular pH, reactivate the anti-oxidant enzymes and control calcium influx so the patient can be rewarmed and reoxygenated without having sustained lethal reperfusion damage. This will all need to be carefully implemented and controlled by the “Reperfusionist”.

The idea of reviving a patient who has already died by using a powerful machine (an ECPR pump) is something straight out of Mary Shelley’s novel! Nonetheless, it is being done with limited success by perfusionists and others in isolated programs throughout the country. But perfusionists need a new type of physician, this “Reperfusionist”, as a partner to help us and lead the way to improved outcomes.

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