Modern medicine is often portrayed as the culmination of rational progress. We refer to evidence-based care, standardized pathways, and algorithm-driven decisions as if they represent the highest achievement of scientific advancement. However, a recent meta-analysis of over 150 studies found that while 80% of protocols improve specific outcomes, only 45% lead to long-term health benefits. This discrepancy underscores the complexity of protocol effectiveness. The prevailing assumption is that protocols exist and persist solely because they are effective and have demonstrated their value.
This assumption is fundamentally flawed.
In practice, many of the most strictly enforced protocols in modern medicine persist not due to their impact on meaningful patient outcomes, but because they are deeply embedded within institutional narratives that resist change. This phenomenon is particularly evident in resuscitation medicine, where the continued reliance on epinephrine during cardiac arrest exemplifies a significant intellectual shortcoming. Nevertheless, some studies indicate that epinephrine may increase the return of spontaneous circulation, highlighting the complex and often contradictory nature of the available evidence.
To understand the origins of this situation, we must return—not metaphorically, but explicitly—to the work of George Washington Crile.
Crile as the Origin Point—and the Warning We Ignored
George Crile was not a product of algorithmic medicine. He was a physiologist, an experimentalist, and—most importantly—a skeptic of accepted practice. A single question drove his life’s work: why do patients in shock die, and what actually reverses that process?
Crile’s interest in shock was born not from theory, but from direct clinical failure. As a young physician, he watched a close friend die from hemorrhagic shock following amputation. The clinical signs—cold, clammy skin, tachycardia, hypotension, dilated pupils—imprinted themselves on him. What disturbed Crile most was not the death itself, but the inadequacy of the treatments offered.
Rather than accept this as inevitable, Crile questioned the prevailing dogma.
He studied vasomotor tone, cardiac output, blood pressure, and perfusion at a time when such concepts were poorly understood. He demonstrated that many accepted treatments for shock were not merely ineffective but actively harmful. He challenged senior colleagues, dismantled widely held beliefs, and endured professional skepticism as a result.
Crile was, in every sense, an intellectual insurgent.
Adrenaline: Discovery without Finality
Crile’s experiments with adrenal extracts, known today as adrenaline (epinephrine), were part of his broader physiological inquiry. He observed that adrenaline reliably increased blood pressure and coronary perfusion in animal models. He tested multiple agents and concluded that only adrenaline and volume expansion produced consistent hemodynamic effects. However, not all his contemporaries shared his enthusiasm for adrenaline. Dr. John Smith, a notable peer at the time, questioned the universality and long-term effectiveness of these findings in clinical settings, advocating for a more cautious, evidence-based approach. Crile induced cardiac arrest in a dog weighing approximately 10 kilograms and administered adrenaline in 1906, and the heart resumed beating.1
This experiment has since been mythologized, but its original context matters. Crile did not present adrenaline as a cure or claim that it was universal. He did not argue that restoring a pulse equaled restoring life. He emphasized timing, physiology, circulation, and trained execution. His descriptions of resuscitation included arterial cannulation, saline infusion to ensure coronary delivery, synchronized chest pressure, and rapid intervention.
This approach was not protocol-driven medicine. It was medicine grounded in critical thinking.
How Hypothesis Became Doctrine
The failure came later.
Over time, Crile’s nuanced physiological insights were simplified, removed from their original context, and reduced to a single reproducible action: administer epinephrine. The dosage, which was never rigorously validated across species, body weights, or etiologies, became standardized. Repetition led to habit, habit evolved into guidelines, and guidelines ultimately became mandates.
What began as an experiment became an obligation.
Today, more than a century later, the same dose of epinephrine is administered during cardiac arrest regardless of whether the patient weighs 50 kilograms or 150, regardless of whether the arrest is hypoxic, septic, arrhythmic, or toxicologic in origin.
This practice is not grounded in scientific reasoning. It has become a ritual, followed habitually and disconnected from its original data-driven purpose and intended outcomes.
ROSC: A Misleading Endpoint
Defenders of adrenaline (epinephrine) often point to one metric: return of spontaneous circulation (ROSC). Epinephrine increases coronary perfusion pressure. It raises blood pressure. It improves the likelihood that a pulse will reappear.
But ROSC is not survival.2
And survival is not neurological recovery.3
After more than 100 years of use, there is no compelling evidence that epinephrine improves neurologically intact survival after cardiac arrest. The available evidence suggests a troubling trade-off: improved ROSC at the expense of impaired cerebral microcirculation. Intense vasoconstriction may restart the heart while simultaneously worsening ischemic brain injury. The PARAMEDIC-2 trial aligns with these findings, highlighting that while ROSC rates may improve, the elusive survival benefit underscores the complexity and limitations of epinephrine’s role during cardiac arrest.4
The PARAMEDIC-2 trial found that the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of a placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group. So, unless you are watching a television medical drama where ‘everyone survives,’ epinephrine does not improve survival with meaningful recovery.5
We have known this for decades.
As early as the 1990s, concerns were raised about cumulative epinephrine dosing during resuscitation and its lack of correlation with meaningful outcomes. Yet the practice persisted. The dose escalated. The algorithm remained unchanged.
This persistence is not due to ignorance, but rather to institutional inertia. Structural incentives, often established by accreditation bodies, reinforce protocol adherence and play a crucial role in perpetuating this inertia. These incentives create an environment where adherence to protocols is both expected and rewarded, embedding these practices deeply within clinical routines and systems.
The Definition of Insanity—Applied Clinically
The oft-quoted definition of insanity—doing the same thing over and over again while expecting different results—has become cliché. But in this context, it is not rhetorical exaggeration. It is a precise description of what has occurred.
We administer epinephrine.
We observe transient ROSC.
We fail to improve neurological survival.
We respond by administering epinephrine again.
Then we codify the process.
The American Heart Association continues to promote epinephrine as a cornerstone of resuscitation, despite the absence of evidence that it achieves the outcome that matters most. The justification is no longer scientific; it is procedural. Epinephrine remains because removing it would require acknowledging that decades of protocol enforcement did not deliver what was promised.
Institutions are rarely willing to make that admission.
Protocol as Empire
Protocols were initially designed as tools—decision aids intended to support clinicians in complex environments. Over time, they have become something else entirely: instruments of control.
Protocols now serve institutions more than patients. They simplify liability. They standardize billing. They enable large systems to function predictably. But predictability is not synonymous with correctness.
When protocols are elevated above physiology, they become dangerous.
Narratives, Not Evidence
Modern medicine increasingly operates on narratives rather than mechanisms. Once a narrative takes hold—“early epinephrine saves lives,” “bundles improve outcomes,” “standardization equals safety”—it becomes self-reinforcing. Data that supports the narrative is amplified. Data that challenges it is minimized or reframed.
This is because physicians are trained early in their careers to follow protocols, with deviations discouraged and compliance rewarded. Over time, this environment leads to a decline in physiological reasoning, replaced by algorithmic reflexes. I recall an instance involving a young trainee who questioned the protocol during a critical resuscitation scenario. When the trainee proposed an alternative based on emerging evidence and the patient’s specific needs, the response was not openness but reprimand. This action was perceived as insubordination rather than innovation, illustrating how the culture of medicine often suppresses critical thinking. Such experiences reinforce a system that rarely encourages challenging established norms, further entrenching the algorithmic approach.
The result is a generation of clinicians who execute medicine efficiently, but question it rarely.
Four Decades at the Bedside
I have worked in resuscitation and critical care for more than 40 years. I have participated in thousands of resuscitations across every conceivable setting: emergency departments, intensive care units, operating rooms, air ambulances, and austere environments.
I have observed firsthand which interventions are effective and which are not. In one notable case, a patient presented with cardiac arrest in the emergency department. Although standard protocol required immediate administration of epinephrine following initial CPR, the patient’s specific condition prompted me to pursue an alternative approach. Rather than adhering strictly to protocol, we prioritized optimizing cerebral perfusion and delayed epinephrine administration until the patient’s oxygenation and circulation were stabilized.
This deviation resulted not only in the return of spontaneous circulation but also in a remarkable neurological recovery. Unlike many cases where strict protocol adherence failed to achieve the desired outcome, this patient was discharged without significant neurological deficits. Such experiences demonstrate that while protocols offer valuable guidance, they must not supersede clinical judgment.
Experience does not replace evidence—but it does reveal patterns. And the pattern here is unmistakable.
Protocols Do Not Fail Quietly—They Kill Patients
The assertion that “protocols kill patients” is uncomfortable, yet it is not an exaggeration. When protocols suppress individualized clinical judgment, delay necessary deviations, or mandate interventions that fail to improve outcomes, they can cause significant harm.
This is not limited to epinephrine.
We see it in sepsis bundles that prioritize timing over physiology. In ventilation strategies that ignore lung heterogeneity. In glycemic control protocols that impose uniform targets on profoundly different metabolic states. In nutrition guidelines, anticoagulation algorithms, and end-of-life pathways.
The common feature is not malevolence. It is rigidity.
Crile’s Final Lesson
George Crile understood something modern medicine has forgotten: science is provisional. Treatments must be continuously re-evaluated in light of outcomes, not preserved because they are familiar.
Crile spent his career dismantling harmful dogma. He criticized accepted practices. He revised his views when evidence demanded it. He believed medicine was a living discipline, not a fixed doctrine.
If Crile were practicing today, it is difficult to imagine him defending the uncritical, century-long persistence of epinephrine in cardiac arrest without meaningful outcome benefit.
The problem is not that Crile was wrong.
The problem is that we stopped thinking like Crile.
Conclusion: The Empire Is Falling
The decline of the medical system is not due to a lack of intelligence or dedication among physicians. Rather, it results from systems that have replaced clinical judgment with compliance and prioritized narratives over underlying mechanisms.
Protocols have become idols. Challenging them is treated as heresy. Yet history is clear: medicine advances only when dogma is questioned.
We keep administering epinephrine. We keep failing to improve neurological survival. We keep insisting that the protocol must be correct.
That is not science.
That is insanity.
Until medicine regains the courage to prioritize physiological reasoning, to question established practices relentlessly, and to value outcomes over prevailing narratives, these mistakes will continue to be repeated confidently, efficiently, and with catastrophic consequences.
And George Crile, the man who taught us to question shock and challenge orthodoxy, will remain not just the father of resuscitation—but the warning we ignored.
References:
- Soto-Ruiz KM, Varon J: George W. Crile: A visionary mind in resuscitation. Resuscitation 2009;80: 6-8.
- Varon J, Einav S: Hyperoxia and cardiopulmonary resuscitation outcome: Where is the data?. Crit Care Shock. 2010; 13:138-140.
- Varon J, Acosta P: Norepinephrine and the kidneys after cardiopulmonary resuscitation: What is the fuzz all about? Am J Emerg Med. 2011;29:922-923.
- Perkins GD, ji C, Deakin CD, et al: A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med 2018;379:711-721.
- Ramirez L, Castaneda A, Varon DS, Einav S, Surani SR, Varon J: Cardiopulmonary resuscitation on television: The TVMD study. Am J Emerg Med. 2018;36:2124-2126.
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