In the Literature

Summary of "Reversal of Propofol-induced Depression of the Hypoxic Ventilatory Response by BK-channel Blocker ENA-001: A Randomized Controlled Trial"

Summary published June 6, 2024

Summary by Jan Ehrenwerth, MD

Anesthesiology | June 2024

Jansen SC, van Lemmen M, Olofsen E, Moss L, Pergolizzi JV Jr, Miller T, Colucci RD, van Velzen M, Kremer P, Dahan A, van der Schrier R, Niesters M. Reversal of Propofol-induced Depression of the Hypoxic Ventilatory Response by BK-channel Blocker ENA-001: A Randomized Controlled Trial. Anesthesiology. 2024 Jun 1;140(6):1076-1087. doi: 10.1097/ALN.0000000000004915. PMID: 38241294; PMCID: PMC11097949.

doi: https://doi.org/10.1097/aln.0000000000004915

  • This study investigates whether the respiratory depression caused by propofol could be reversed by infusing a BK-channel blocker-ENA-001.
  • Since propofol decreases the ventilatory response to hypoxemia, the authors theorized that by administering an agnostic respiratory stimulant, they could reverse the propofol induced depression of the hypoxic ventilatory response (PVR).
  • The carotid body is the main oxygen sensor in the body, such that hypoxemia will result in a ventilatory response that increases pulmonary oxygen uptake.
  • ENA-001 is a respiratory stimulant that acts at the carotid bodies to increase ventilation by blocking the Ca++ activated K+ channels (BK-channels).
  • The authors studied twelve healthy volunteers (ages 18-55 years), in a randomized placebo controlled double blind crossover study. The subjects were studied on three separate occasions, where low and high doses of ENA-001 and placebo were administered.
  • Each session began with the study drug alone, followed by low dose propofol and then high dose propofol. The subjects breathed a hypoxic gas mixture to decrease their O2 saturation to 80%. The ventilatory response to hypoxia was tested at both low and high levels of end tidal PCO2.
  • The results showed a significant increase in HVR with high dose ENA-001as compared to placebo. However, low dose ENA-001did not show a significant change in HVR compared to placebo. This effect was maintained over the entire range of propofol blood concentrations.
  • This study demonstrates that the decrease in HVR caused by a centrally acting drug (propofol), can be reversed by a drug that stimulates the carotid bodies.
  • Even though the sample size in this study was small, the authors did an excellent job in designing the study to test their theory. Although further studies are indicated, this newer class of drug (BK-channel blocker) has exciting possibilities to enhance patient safety.
Continue Reading

Follow & Subscribe!