Primum non nocere or how to resolve drug-induced respiratory depression.

1261 June 2013 Drug-induced Respiratory Depressidon and Ampakines MANY of the drugs used currently by anesthesiologists produce serious side effects, of which respiratory depression is one that is potentially fatal. Although we know that anesthetics and opioids are relatively safe in the hands of anesthesiologists and other well-trained anesthesia specialists (although there are always potential problems), the risks from the use of these drugs are potentially increasing with the growing trend of their use by nonanesthesia caregivers. Consequently, with the increased use and prescription of potent drugs that depress the ventilatory control system and/ or increase the probability of an upper airway patency problem, one may expect to see an increase in morbidity and mortality, especially when monitoring is insufficient and/or the caregiver is insufficiently able to diagnose or treat respiratory depression. In the current issue of ANesthesIologY, Ren et al.1 report a study on the effect of an ampakine on propofol-induced respiratory depression and fatal apneas in rodents. they demonstrate elegantly that coadministration of the ampakine CX717 attenuates respiratory depression induced by propofol. this group previously demonstrated in rats that the same ampakine also alleviates opioid-induced respiratory depression (oIRD) and suppression of hypoglossal motoneuron activity that suggest the ability of this drug to overcome opioid-induced impairment of airway patency.2,3 one important feature of the attenuation by CX717 of oIRD is that this effect was not accompanied by a significant reduction in analgesia.4 Ampakines act at AMPA (amino-3-hydroxy-5-methyl-D-aspartate) receptors. glutataminergic transmission through AMPA receptors within the brainstem respiratory centers, most importantly the pre-Bötzinger complex, is essential for rhythmogenesis and induction of increased respiratory frequency. Various ampakines that interact with the AMPA receptor have been studied in respiratory systems; the most studied agent is CX717. A major advantage of CX717 is that it is available for human use and has been tested for safety and efficacy in the treatment of human attention deficit hyperactivity disorders and Alzheimer disease. Indeed, a proof of concept study with CX717 in human volunteers demonstrated that a single oral dose of CX717 (1500 mg) reduced low-dose (plasma concentration 100 ng/ml) alfentanil– induced respiratory depression without significant effects on analgesia.4 these data suggest that, in patients, the coadministration of an ampakine during exposure to potent opioids and anesthetics such as propofol will be a major step forward in the prevention of drug-induced respiratory depression without negating their analgesic (and possibly hypnotic) effects. evidently, further clinical studies are required showing that CX717 works in patients as well and is not associated with serious side effects. Primum Non Nocere or How to Resolve Drug-induced Respiratory Depression