Ventral cervical epidural electrical stimulation failed to increase respiratory activity in anesthetized humans...

Respiratory depression is the leading cause of death during opioid overdoses. Epidural electrical stimulation (EES) may facilitate rhythmic motor activities such as locomotion and respiration. We investigated whether tonic, submotor threshold, EES of the ventral cervical spinal cord would activate muscles innervated by motor neurons outside the ventral cervical spinal site of stimulation and increase tidal volume, respiratory frequency, and decrease end-tidal Pco₂, or activate a more restricted set of muscles innervated by motor neurons near the stimulating electrodes. We studied 24 patients who were anesthetized with propofol and low-dose or high-dose remifentanil for treatment of anterior cervical spinal impingement. Cervical EES was delivered between cervical levels 3 to 7 (C3 to C7) for up to 90 s at an intensity ranging from 0.5 mA to 5 mA and a frequency of 5, 30, or 90 Hz at each dose of remifentanil. Ventral cervical EES did not reset the respiratory rhythm. There were no significant changes, on average, in tidal volume, respiratory frequency, or end-tidal Pco₂ during or after ventral cervical EES. In contrast, dorsal cervical EES reset the respiratory rhythm, augmented respiratory activity beyond the period of stimulation, and increased both tidal volume and respiratory frequency and decreased end-tidal Pco₂ in a similar, previous study in anesthetized humans. These observations suggest that the mild to moderate intensity, ventral cervical EES at frequencies < 100 Hz cannot access ventral motor neurons directly or activate interneuronal circuits that might increase motor neuron output indirectly during opioid-induced respiratory depression.NEW & NOTEWORTHY Submotor threshold, dorsal cervical epidural stimulation increased ventilation during opioid-induced respiratory depression by augmenting afferent information that accessed the pontomedullary and spinal circuits driving respiratory motor neurons. Ventral cervical epidural stimulation was unable to achieve a similar effect; ventral stimulation, at the field strength and frequencies tested, did not access or augment ventral respiratory motor neurons during opioid-induced respiratory depression.