Modulation of Cerebral Function by Muscle Afferent Activity, with Reference to Intravenous Succinylcholine (Reprinted from Anesthesiology, vol 71, pgs 87-95, 1989)

By the mid-1980s, it was widely assumed that if the depolarizing muscle relaxant, succinylcholine, given IV, produced increases in intracranial pressure, it did so because fasciculations produced increases in intrathoracic and central venous pressures that were transferred to the brain; however, there was no direct evidence that this was true. In contrast, we explored the possibility that the succinylcholine effect on the brain was explained by the afferentation theory of cerebral arousal, which predicts that agents or maneuvers that stimulate muscle stretch receptors will tend to stimulate the brain. Our research in tracheally intubated, lightly anesthetized dogs discovered that IV succinylcholine (which does not cross the blood-brain barrier) produced a doubling of cerebral blood flow that lasted for 30 min and corresponded to activation of the electroencephalogram and increases in intracranial pressure. Later, in our Classic Paper, we were able to assess simultaneously cerebral physiology and afferent nerve traffic emanating from muscle stretch receptors (primarily muscle spindles). We affirmed that the cerebral arousal response to succinylcholine was indeed driven by muscle afferent traffic and was independent of fasciculations or increases in intrathoracic or central venous pressures. Later research in complementary models demonstrated that endogenous movement (e.g., coughing, hiccups) produced a cerebral response very similar to IV succinylcholine, apparently as a result of the same muscle afferent mechanisms, independent of intrathoracic and central venous pressures. Thus, the importance of afferentation theory as a driver of the cerebral state of arousal and cerebral physiology during anesthesia was affirmed.

Automated summary

It was previously believed that the muscle relaxant succinylcholine increased intracranial pressure indirectly through the increase in intrathoracic and central venous pressures caused by muscle fasciculations. However, research on tracheally intubated dogs showed that intravenous succinylcholine directly doubled cerebral blood flow, activated the electroencephalogram, and increased intracranial pressure, indicating that the effect was driven by muscle afferent traffic rather than increased pressures. Further studies demonstrated that endogenous movements, like coughing and hiccups, produced similar cerebral responses through muscle afferent mechanisms. This affirmed the significant role of afferentation theory in anesthesia-induced cerebral arousal and physiology.