In Response

Abstract

Nathan et al. 1 raise interesting points for discussion that we address in order: First, the conclusion of our article states that "Dexmedetomidine appears to be a reasonable choice for sedation of children with pulmonary hypertension receiving chronic pulmonary vasodilator therapy." 2 Our study excluded subjects with unstable, untreated pulmonary hypertension (PH), so, as discussed in our article, the conclusion was not as broad as suggested by Nathan et al. 1 Second, we presented the data on reactivity of pulmonary vascular resistance (PVR) to oxygen and nitric oxide to demonstrate that pulmonary vascular reactivity was present in our subjects. We cited an article supporting the concept that patients with PH responding to nitric oxide with pulmonary vasodilation also respond to appropriate stimuli with pulmonary vasoconstriction. 3 Therefore, we believe that our subjects retained the ability to react with pulmonary vasoconstriction if dexmedetomidine had provided such a stimulus.Third, the fact that our subjects were receiving chronic pulmonary vasodilator therapy was discussed in our article, and readers were presented with the caveat that "this chronic therapy might have blunted any pulmonary vasoconstrictive effects of dexmedetomidine." 2 Fourth, there is a difference between attenuating vasoconstriction caused by a noxious physical stimulus and vasoconstriction caused by a pharmacodynamic effect of a drug. Hickey 4 demonstrated that 25 mcg/kg fentanyl attenuated the PVR response to airway instrumentation. Blunting the sensation and response to noxious physical stimuli is a basic function of opioids and is not to be confused with pulmonary vasodilation or α-adrenergic blockade. Hickey 5 also demonstrated that fentanyl has no effect on PVR or pulmonary artery pressure (i.e., is not a pulmonary vasodilator), study population was relatively modest (and all patients were receiving single or multi-agent anti-PH therapy). Third, remifentanil infusion might have prevented a further increase in PVR with DEX, because opioids can attenuate an increase in PVR secondary to airway instrumentation. 2 Thus, these results may not describe how DEX will affect every patient with PH especially those with a more severe form of this disease.Of some relevance, we recently stopped a Food and Drug Administration monitored study evaluating the effect of DEX on PVR in children with PH [clinicaltrials. gov-NCT 01072643]. Eligible children (4 of 24 screened) underwent anesthesia with sevoflurane in oxygen/air for placement of vascular access after which they were awakened (University of Michigan Sedation Scale of 0-1). Hemodynamic measurements were obtained during spontaneous ventilation of room air (T0), repeated after a DEX bolus (1 mcg/kg over 10 minutes, T1), and then again at 30 minutes after a DEX infusion (0.7 mcg/ kg/h, T2). The study was terminated due to increased PVR in subject 4 from T0-T1 reaching the level of a predetermined stopping rule, with side effects including premature ventricular complexes, bradycardia (<60 bpm),...