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Anesthesiology Sep 2014Opioid-induced respiratory depression is potentially lethal. GAL021 is a calcium-activated potassium (BKCa) channel blocker that causes reversal of opioid-induced... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Opioid-induced respiratory depression is potentially lethal. GAL021 is a calcium-activated potassium (BKCa) channel blocker that causes reversal of opioid-induced respiratory depression in animals due to a stimulatory effect on ventilation at the carotid bodies. To assess in humans whether GAL021 stimulates breathing in established opioid-induced respiratory depression and to evaluate its safety, a proof-of-concept double-blind randomized controlled crossover study on isohypercapnic ventilation (study 1) and subsequent double-blind exploratory study on poikilocapnic ventilation and nonrespiratory end points (study 2) was performed.
METHODS
In study 1, intravenous low- and high-dose GAL021 and placebo were administrated on top of low- and high-dose alfentanil-induced respiratory depression in 12 healthy male volunteers on two separate occasions. In study 2, the effect of GAL021/placebo on poikilocapnic ventilation, analgesia, and sedation were explored in eight male volunteers. Data are mean difference between GAL021 and placebo (95% CI).
RESULTS
Study 1: Under isohypercapnic conditions, a separation between GAL021 and placebo on minute ventilation was observed by 6.1 (3.6 to 8.6) l/min (P < 0.01) and 3.6 (1.5 to 5.7) l/min (P < 0.01) at low-dose alfentanil plus high-dose GAL021 and high-dose-alfentanil plus high-dose GAL021, respectively. Study 2: Similar observations were made on poikilocapnic ventilation and arterial pCO2. GAL021 had no effect on alfentanil-induced sedation, antinociception and no safety issues or hemodynamic effects became apparent.
CONCLUSION
GAL021 produces respiratory stimulatory effects during opioid-induced respiratory depression with containment of opioid-analgesia and without any further increase of sedation. Further studies are needed to confirm these preliminary data.
Topics: Adolescent; Adult; Alfentanil; Analgesia; Analgesics, Opioid; Cross-Over Studies; Double-Blind Method; Doxapram; Healthy Volunteers; Hemodynamics; Humans; Large-Conductance Calcium-Activated Potassium Channels; Male; Middle Aged; Potassium Channel Blockers; Respiratory Insufficiency; Triazines
PubMed: 25222672
DOI: 10.1097/ALN.0000000000000367 -
American Journal of Perinatology Oct 2014The aim of the article is to provide an update on medication use in infants admitted to the neonatal intensive care unit (NICU) in the United States and examine how use...
OBJECTIVE
The aim of the article is to provide an update on medication use in infants admitted to the neonatal intensive care unit (NICU) in the United States and examine how use has changed over time.
STUDY DESIGN
We performed a retrospective review (2005-2010) of a large prospectively collected administrative database.
RESULT
Medications most commonly administered during the study period were ampicillin, gentamicin, caffeine citrate, vancomycin, beractant, furosemide, fentanyl, dopamine, midazolam, and calfactant (56-681 exposures per 1,000 infants). Those with the greatest relative increase in use included azithromycin, sildenafil, and milrinone. Medications with the greatest relative decrease in use included theophylline, metoclopramide, and doxapram.
CONCLUSION
Medication use in the NICU has changed substantially over time, and only 35% of the most commonly prescribed medications are Food and Drug Administration -approved in infants.
Topics: Drug Therapy; Drug Utilization; Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Intensive Care, Neonatal; Male; Retrospective Studies; United States
PubMed: 24347262
DOI: 10.1055/s-0033-1361933