Combination therapy: The patient's view
One consequence of the growing understanding of the biochemical pathways involved in brain injury resulting from cardiac arrest, stroke, and brain trauma is that there is an increasing consensus among researchers that combination therapy is the most logical treatment for the multifactorial injury mechanisms responsible for neuronal death. In this context, combination therapy can mean either combining different forms of treatment, such as hypothermia and a neuroprotective agent, or the combination of multiple neuroprotective agents. But despite encouraging results with combination therapy in animal models, and disappointing outcomes for single neuroprotective agents (such as the recent free radical spin trap agent NXY-059) in human clinical trials, there are no indications that the current trend of investigating just one neuroprotective agent will be reversed soon.
One obstacle for successful combination treatment that is not often addressed is that cardiac arrest, stroke, and brain trauma are acute events that do not allow a vocal pro-active role of the patient at the time that this could benefit him. During the immediate post-insult period when the molecular events leading to neuronal death, and even higher brain death, play out, most patients are not able to communicate their wishes, or are in a coma. As a result, the patient is not present at the time when the most important decisions about his survival as a person are being made.
This predicament is different from patients suffering from serious but chronic diseases such as AIDS and cancer. In his book “Surviving Terminal Cancer: Clinical Trials, Drug Cocktails, and Other Treatments Your Oncologist Won’t Tell You About” psychology professor Ben Williams documents how he improved his odds of surviving a glioblastoma multiforme brain tumor by researching and pursuing his own treatment, which consists of a combination of conventional and “alternative” treatments.
Williams’ successful case of personalized combination therapy does not present strict scientific evidence that his treatment is the cause of his remarkable recovery (so far), but it does highlight the general benefits that may be obtained when patients demand some degree of control over their choice of treatments. Williams stresses that patients such as himself may have much to gain, and not much too lose, from pursuing such an experimental “cocktail” approach. A similar situation applies to patients who are at risk of severe brain injury and cannot afford to wait until the mechanisms and comparative efficacies of each individual component of a neuroprotective cocktail have been thoroughly investigated.
How can such an outcome driven treatment of cerebral ischemia gain acceptance? Since the patient will not “be there” to investigate and demand unorthodox experimental treatments, he can only influence his odds by leaving advance directives to medical care givers and relatives to request that such treatments are given to him. Such measures can only have a chance of succeeding, however, if experimental treatment options are documented for these patients.
In contrast, combinational pharmacotherapy and hypothermia have been core components of human cryopreservation stabilization protocol for many years. To date, researchers involved in cryonics have made record achievements in normothermic cerebral resuscitation and (ultra)profound hypothermic resuscitation. The applications of such research should not be limited to minimizing brain injury in cryonics patients but should be shared with the general public to help build a “supply” side of experimental treatments that can be consulted by medical care givers and relatives of the patient.
Individuals who are signed up for cryonics have a personal interest in stimulating such research, its documentation and dissemination because acute insults such as cardiac arrest, stroke, and brain trauma can produce (higher) brain death before the individual will present for human cryopreservation in the future. Indeed, cryonics may offer the only chance of personal survival for patients who are at risk of major brain damage if they are resuscitated and left to live at room temperature.