The Lazarus Sleep

How Cortisone and Glucose Awakened Barbiturate Victims

Introduction: The Deadly Lullaby

In the 1950s, barbiturates were the "sleeping pills of choice"—and often, of death. With overdose victims slipping into irreversible comas, physicians faced a grim reality: no antidote existed. Then came a radical idea: What if the solution wasn't waking patients up, but putting them into a deeper, healing sleep? This is the story of a daring 1957 experiment that used cortisone and glucose to reinduce sleep in barbiturate-poisoned patients, flipping medical logic on its head 7 .

Barbiturates: A Double-Edged Sword

Barbiturates like phenobarbital suppress brain activity by enhancing GABA (gamma-aminobutyric acid), the brain's primary inhibitory neurotransmitter. This calms neural "noise" but can fatally silence vital functions:

Long-acting types

(e.g., phenobarbital): Effects last 6–12 hours; lethal dose = 6–10 g 4 6 .

Short-acting types

(e.g., secobarbital): Rapid brain penetration; lethal dose = 1–5 g 4 .

Overdose causes a "neural blackout": suppressed breathing, plummeting blood pressure, and coma. By the 1950s, this accounted for ~70% of fatal drug poisonings 6 .

Cortisone's Paradoxical Role

Cortisol (and its synthetic form, cortisone) is best known as the "stress hormone." But it also governs sleep-wake cycles:

Normal rhythm

Peaks at dawn to promote alertness; dips at night for sleep onset 3 5 .

High cortisol disrupts sleep

Elevates alertness, fragments deep sleep, and reduces REM 1 .

Yet in barbiturate coma, the absence of stress signaling became the problem. Researchers hypothesized that jump-starting cortisol pathways could reboot stalled brain circuits 7 .

The 1957 Experiment: Sleep as Salvation

In a landmark trial, doctors treated comatose barbiturate patients with intravenous glucose and cortisone—aiming not to rouse them, but to trigger a therapeutic sleep state 7 .

Methodology: A Step-by-Step Rescue

  • Secured airways to prevent suffocation.
  • Administered IV fluids to counter shock.

  • Stomach lavage with 1:5000 potassium permanganate to oxidize drug residues 4 .
  • Activated charcoal to bind intestinal toxins.

  • Cortisone IV: 100–200 mg to reactivate adrenal signaling.
  • 50% glucose IV: Counteracted hypoglycemia from liver failure.

  • Alkalinization: IV sodium bicarbonate (5% solution) to convert barbiturates into water-soluble forms for excretion 4 6 .
  • Forced diuresis: Mannitol to flush toxins via kidneys.

Results: From Coma to Recovery

Patient Group Survival Rate Time to Consciousness
Cortisone/glucose + standard care 92% 6–12 hours
Standard care alone 68% 24+ hours

Table 1: Survival outcomes in barbiturate coma patients (adapted from 7 )

The cortisone-glucose group showed:

  • Faster toxin clearance: 40% reduction in blood barbiturate levels within 4 hours.
  • Stabilized breathing: Respiratory rates normalized 2x quicker.
  • Natural sleep rebound: 80% entered 4+ hours of deep sleep before waking.

Why this worked:

  • Glucose countered drug-induced metabolic shutdown.
  • Cortisone reactivated mineralocorticoid receptors (MR), restoring neural excitability 1 .

The Science of Sleep Reinduction

Cortisone didn't just reverse poisoning—it leveraged the body's innate recovery mechanisms:

1. Glucose: The Brain's Emergency Fuel

Barbiturates starve neurons of energy. Glucose infusion:

  • Prevents hypoglycemia-induced brain damage.
  • Spurs ATP production to power detox enzymes .
2. Cortisone: Resetting Circadian Chaos
Sleep Parameter Barbiturate Coma Post-Cortisone
Slow-wave sleep <5% 20–30%
REM sleep 0% 5–10%

Table 2: Cortisone's impact on sleep architecture (data from 1 7 )

- MR receptors in the hippocampus responded to cortisone by boosting slow-wave sleep—critical for brain repair 1 .
- This countered barbiturates' REM-suppressing effects, allowing gradual neural recovery.

The Scientist's Toolkit: Key Reagents in Barbiturate Research

Reagent Function Mechanism
Cortisone acetate Reactivates stress signaling Binds MR/GR receptors to restore neural excitability
50% dextrose Rapid glucose delivery Reverses metabolic shock; fuels ATP synthesis
Sodium bicarbonate Urine alkalinization Ionizes barbiturates for renal excretion
Mannitol Osmotic diuretic Forces toxin clearance via kidneys
Potassium canrenoate MR blocker (control) Blocks cortisol's effects; proves MR's role 1

Table 3: Core reagents in barbiturate detox research 1 4 7

Legacy and Modern Insights

This experiment pioneered two revolutions:

  1. Hormonal resuscitation: Today, IV hydrocortisone is standard for septic shock and adrenal crisis.
  2. Circadian medicine: We now time cortisone doses to mimic natural rhythms—e.g., morning dosing to avoid nighttime sleep disruption 3 .
But caution remains:
  • Long-term cortisone causes insomnia, weight gain, and psychosis 2 5 .
  • Barbiturates were phased out for safer alternatives (e.g., benzodiazepines) after their toxic risks became clear 6 .

Conclusion: The Sleep That Heals

The 1957 trial revealed a profound truth: sometimes, deeper sleep—not wakefulness—is the path to resurrection. By harnessing cortisone's circadian power and glucose's lifesaving energy, physicians turned the body's natural defenses into a weapon against poisoning.

As we unravel cortisol's dual role in stress and sleep, one principle endures: biology's "flaws" often hide its most brilliant solutions.

"In the depths of induced sleep, the brain finds its way back to life."

References