“Alcohol is the anesthesia by which we endure the operation of life.”---George Bernard Shaw
Anesthesia suffers for lack of an effective theory that enables the alteration of anesthetic technique to optimize surgical outcome. Before the discovery of anesthesia, surgery caused an excruciating "surgical stress syndrome" that entailed fever, tachycardia, hypertension, delirium, stroke, heart attack, breathing problems, organ failure, and exaggerated pain that reached peak intensity in about 48 hours and was often lethal. Morton's discovery of anesthesia was actually the invention of a glass device that enabled practical ether administration that enabled surgical survival. Though general anesthesia minimizes mortality, it fails to eliminate postoperative morbidity, including fever, laryngospasm, cancer, and heart disease. Most attempts to explain the nature of anesthesia assume that surgical stress is exclusively mediated by the brain, and ignore the effects of tissue disruption and spinal cord pathways that bypass the brain. The MSM discovery enables a fresh theory of anesthesia, analgesia and allostasis that addresses these shortcomings.
Consciousness continuously evaluates sensory information to detect environmental danger, including sight, sound, smell, and nociception, which is nervous sensation generated by tissue disruption sensors (nociceptors) in peripheral tissues. These communicate with the brain via peripheral sensory nerves and spinal cord nociception pathways. Consciousness perceives nociception as pain, and partial inhibition of consciousness abolishes the ability of consciousness to perceive nociception as pain.
Spinal cord nociception pathways communicate directly with sympathetic ganglia in the chest and abdomen via “internuncial" neurons. Anesthesia has little effect on this pathway. Consciousness inhibits spinal cord nociception pathways via descending pathways from the brain. Anesthesia abolishes consciousness and eliminates cortical modulation of spinal cord nociception.
The descending systems that modulate the transmission of ascending pain signals. These modulatory systems originate in the somatic sensory cortex, the hypothalamus, the periaqueductal gray matter of the midbrain, the raphe nuclei, and other nuclei of the rostral ventral medulla. Complex modulatory effects occur at each of these sites, as well as in the dorsal horn.
From: The Nociceptive Components of the Thalamus and Cortex
Cover of Neuroscience
Neuroscience. 2nd edition.
Purves D, Augustine GJ, Fitzpatrick D, et al., editors.
Sunderland (MA): Sinauer Associates; 2001.
The emotional mechanism works closely with consciousness and maintains a permanent audiovisual memory of all sensory information. Both normal sleep and anesthesia abolish consciousness and halt memory accumulation. During normal sleep, the dreaming mechanism evaluates accumulated memories to identify dangerous environmental circumstances. It automatically induces fear when it detects dangerous circumstances, and continually alters its activity in accord with accumulating memories. Fear induces sympathetic nervous system hyperactivity via hypothalamic pathways independent of the spinal cord. Emotional memory is normally suppressed and remains subconscious, but under certain circumstances it can mimic pain in the absence of nociception. This may explain PTSD, neurosis, and phantom limb pain.
Surgical stress induces MSM hyperactivity that manifests as the surgical stress syndrome via three synergistic pathways:
1. The tissue disruption pathway. Surgery releases tissue factor into systemic blood circulation, thereby harmfully activating factor VII.
At present, there are no agents or techniques available that can inhibit the tissue disruption pathway.
2. The cognitive pathway. Pain, fear, and apprehension activate harmful sympathetic nervous system activity that exaggerates factor VIII activity via hypothalamic pathways that bypass the spinal cord.
3. The nociception pathway. Nociception induces harmful sympathetic nervous system activity that exaggerates factor VIII activity via spinal cord nociception pathways that remain active in the absence of brain activity.
Anesthesia is the elimination of consciousness. Inhalation anesthetics, Propofol, benzodiazepines, barbiturates, and other hypnotic agents exert their benefits by quenching consciousness and emotion, which reduces harmful sympathetic activity induced via the cognitive pathway. Anesthesia also abolishes cortical modulation (inhibition) of spinal cord nociception but does not inhibit nociception, so that anesthesiology alone dangerously exaggerates surgical nociception.
Analgesia inhibits the nociception pathway but has little effect on the cognitive pathway, consciousness, or descending cortical pathways that inhibit spinal cord nociception.
Opioid analgesics (morphine, fentanyl, Sufentanil etc.) exert their beneficial effects by directly inhibiting spinal cord nociception pathways, but they have little effect on consciousness, which continues to perceive danger via remaining sensations.
Local analgesics (lidocaine, marcaine, prilocaine, etc.) exert their beneficial effects by inhibiting the nociception pathway. They directly disrupt the function of nociceptors, peripheral nerves, and spinal cord, but they have little effect on consciousness, and do not prevent harmful cognitive pathway activity induced by the remaining sensations.
NSAID agents (aspirin, ketorolac, etc.) inhibit nociceptors, and thereby inhibit the nociception pathway, but they have little effect on the cognitive pathway.
Neither anesthesia nor analgesia alone can effectively prevent harmful surgical sympathetic hyperactivity.
Synergistic combinations of anesthesia and analgesia can effectively prevent harmful sympathetic hyperactivity, but such combinations abolish respiratory drive and necessitate respiratory support. CO2 supplementation counteracts opioid respiratory depression and optimizes cardiorespiratory function, tissue perfusion, tissue oxygenation, organ function, and organ protection. Therefore, general anesthesia with opioid and CO2 supplementation offers the simplest, safest and most reliable means to minimize surgical stress and optimize outcome. The development of a tissue factor antidote that could be administered at the conclusion of surgery, when hemostasis is assured, would abolish the surgical stress syndrome altogether and re-revolutionize surgery.