Four Forgotten Giants of Anaesthesia History: Did a CO2 Error Change Medicine?
Medical history is often presented as a straightforward march towards progress. Yet every so often an author argues that an entire profession may have taken a wrong turn.
That is precisely the claim made by Lewis S. Coleman in his 2016 paper Four Forgotten Giants of Anesthesia History.
The paper is both a historical review and a controversial reinterpretation of the development of modern anaesthesia. While many of its historical descriptions are well documented, its central conclusions challenge current mainstream anaesthetic practice and remain disputed.
The forgotten pioneers
Coleman argues that four early twentieth-century figures laid the foundations for a safer, more physiological approach to anaesthesia before their work was largely abandoned.
George Washington Crile (1864–1943)
Crile is presented as the true father of modern anaesthesia rather than simply a pioneering surgeon.
Among his achievements were:
- introducing blood pressure monitoring during surgery
- recognising that pain and fear worsen surgical outcomes
- promoting effective pain relief before, during and after operations
- emphasising the importance of reducing surgical stress rather than simply rendering patients unconscious.
Coleman argues that Crile appreciated something modern medicine has only recently begun to rediscover: controlling the body’s stress response may be just as important as the surgery itself.
Yandell Henderson (1873–1944)
Henderson, a Yale physiologist, occupies the central role in Coleman’s argument.
He believed carbon dioxide (CO₂) was not merely a waste gas but an essential regulator of:
- breathing
- circulation
- oxygen delivery to tissues
- cardiac performance.
According to Coleman, Henderson demonstrated that modest increases in CO₂ could improve tissue oxygenation, stimulate breathing and reduce complications following surgery.
Dennis Jackson (1878–1980)
Jackson developed the first practical closed-circuit anaesthesia machines, allowing patients to rebreathe anaesthetic gases while removing excess CO₂ using soda lime.
These innovations became the basis of modern anaesthesia machines.
John Silas Lundy (1894–1973)
Lundy pioneered balanced anaesthesia, combining multiple drugs rather than relying on a single anaesthetic agent.
He also helped introduce:
- intravenous induction
- recovery rooms
- blood banks
- improved anaesthesia training.
The great turning point
Coleman argues that early anaesthetists commonly combined:
- morphine for pain control
- ether anaesthesia
- modest CO₂ supplementation.
This approach attempted to minimise surgical stress while maintaining normal physiology.
However, problems arose because primitive equipment sometimes delivered dangerously high CO₂ concentrations. Patients occasionally suffered fatal episodes of what Coleman believes was carbon dioxide-induced asphyxiation.
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The key question became:
Were these deaths caused by CO₂ poisoning—or by oxygen deprivation resulting from excessive CO₂?
Coleman argues the profession reached the wrong conclusion.
Ralph Waters and the birth of modern anaesthesiology
Ralph Waters is widely regarded as the founder of academic anaesthesiology.
He introduced several innovations that remain standard today:
- endotracheal intubation
- muscle relaxants
- controlled mechanical ventilation
- deliberate hyperventilation during surgery.
Waters believed excessive CO₂ was dangerous and described it as a toxic waste product.
Coleman argues this assumption fundamentally changed the direction of anaesthesia for nearly a century.
The carbon dioxide controversy
The heart of the paper concerns the physiological role of carbon dioxide.
Coleman argues that:
- CO₂ itself is not inherently toxic at clinically moderate levels.
- Hyperventilation removes too much CO₂ from the body.
- Low CO₂ reduces oxygen release from haemoglobin via the Bohr effect.
- Reduced CO₂ suppresses the body’s normal drive to breathe.
- Excessive hyperventilation may contribute to postoperative complications.
He further argues that many historical reports of “carbon dioxide poisoning” were actually cases of severe oxygen deprivation caused by primitive equipment and poor monitoring.
Modern pulse oximetry and capnography, he suggests, would have distinguished between these possibilities.
Hyperventilation under scrutiny
One of Coleman’s strongest criticisms concerns routine mechanical hyperventilation during anaesthesia.
He argues that excessive ventilation may:
- reduce tissue oxygen delivery
- impair blood flow to vital organs
- increase blood viscosity
- worsen postoperative respiratory depression
- interfere with opioid metabolism.
He believes maintaining mildly elevated CO₂ levels—sometimes called permissive hypercapnia—could improve outcomes in many patients.
Interestingly, modern intensive care medicine has already adopted permissive hypercapnia in selected situations, particularly in patients with severe lung injury, although for reasons that differ from Coleman’s broader theory.
Why were these ideas forgotten?
Coleman argues that once Waters established anaesthesiology as an independent medical specialty, his students spread his approach throughout medical schools across North America.
As a result:
- hyperventilation became standard practice
- CO₂ supplementation disappeared
- opioid use became more cautious
- earlier physiological concepts were largely forgotten.
Whether this represents scientific progress or historical error forms the central debate of the paper.
A challenge to accepted history
Coleman goes beyond historical analysis.
He argues that many modern complications—including postoperative respiratory depression, poor pain control and excessive reliance on muscle relaxants—can ultimately be traced back to misunderstanding carbon dioxide physiology.
This is an ambitious claim and one that has not been accepted by mainstream anaesthesiology.
The scientific perspective
Although the paper raises interesting historical questions, many of its conclusions remain controversial. Modern anaesthetists already individualise ventilation according to each patient’s condition, and contemporary medicine recognises that both excessive and insufficient carbon dioxide levels can be harmful depending on the clinical situation.
Final thoughts
Coleman’s paper serves as a reminder that scientific progress is rarely linear. Medical practice evolves through debate, competing theories and continual re-evaluation of evidence.
Whether or not his reinterpretation proves correct, the article highlights an important principle: long-standing assumptions deserve periodic re-examination in the light of improved technology and new evidence.
History shows that scientific consensus can change—but only when supported by rigorous experimental data.
Reference
Coleman LS. Four Forgotten Giants of Anesthesia History. Journal of Anesthesia and Surgery. 2016;3(2):1–17.