Professor Drummond makes a good point that apnea induced by propofol does not occur entirely through its actions at γ-aminobutyric acid–mediated synapses in the dorsal and ventral respiratory groups in the medulla and pons. However, he further writes, “I suggest that loss of consciousness mediated by suppression of the arousal centers, which is also considered by Reshef et al.,1 to be a more likely cause of apnea in these circumstances. In conscious subjects, respiration is generally sustained not by chemosensor stimulation, but by consciousness itself…After a bolus of IV agent, loss of consciousness often causes apnea, because there is, for a short time, no alternative stimulus to provide respiratory drive.” These statements do not offer any specific circuit mechanism as to how loss of consciousness “causes” apnea.
What is highly plausible is that bolus administration of propofol leads to a preponderance of γ-aminobutyric acid–mediated inhibition in the brainstem. As we have pointed out previously, the brainstem component of loss of consciousness following bolus administration of propofol, is due most likely to its actions at the γ-aminobutyric acid–mediated projections from the preoptic area of the hypothalamus on to the arousal centers.2–4 In addition, there is extensive γ-aminobutyric acid–mediated circuitry in the brainstem such that when an agent like propofol is administered as a bolus, it acts indiscriminately at all of these circuits, offering a myriad of possibilities to inactivate the respiratory centers.5–7 More work is needed to trace out precisely the relationship between brainstem inactivation due to γ-aminobutyric acid–mediated mechanisms and apnea. We agree that bolus administration of propofol leading to apnea is different from an inhalational induction in which the patient becomes unconscious but can continue to breath.
Supported by grant Nos. P01-GM118269 and R01-GM104948 from the National Institutes of Health, Bethesda, Maryland, and funds from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.
The author declares no competing interests.