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A Word of Caution

Dexmedetomidine and Pulmonary Hypertension

Nathan, Aruna T., FRCA; Nicolson, Susan C., MD; McGowan, Francis X., MD

doi: 10.1213/ANE.0000000000000236
Letters to the Editor: Letter to the Editor
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Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania nathan@email.chop.edu

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To the Editor

We have several concerns regarding the recent article by Friesen et al.1 who conclude that dexmedetomidine (DEX) has minimal effect on pulmonary vascular resistance (PVR) in children with pulmonary hypertension (PH) and is therefore safe in this population. First, responsiveness to inhaled nitric oxide (iNO) was among the inclusion criteria, and we are not aware that intact pulmonary vasodilator response(s) guarantee intact constrictor capacity as well. Second, the degree of PH in the 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), and hypotension; PVR increased during DEX to a less severe degree in all (3 of 4) the remaining subjects (Table 1).

Table 1

Table 1

We suggest that it is premature to conclude that DEX does not adversely affect PVR, particularly in children with severe or brittle PH; right ventricular dysfunction is an additional concern. A multisite, randomized, controlled trial evaluating the safety of DEX, including its effect on PVR in children with varying degrees of PH is necessary before concluding that DEX is safe in all children with PH.

Aruna T. Nathan, FRCA

Susan C. Nicolson, MD

Francis X. McGowan, MD

Department of Anesthesiology and Critical Care Medicine

The Children’s Hospital of Philadelphia

Perelman School of Medicine

University of Pennsylvania

Philadelphia, Pennsylvania

nathan@email.chop.edu

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REFERENCES

1. Friesen RH, Nichols CS, Twite MD, Cardwell KA, Pan Z, Pietra B, Miyamoto SD, Auerbach SR, Darst JR, Ivy DD. The hemodynamic response to dexmedetomidine loading dose in children with and without pulmonary hypertension. Anesth Analg. 2013;117:953–9
2. Hickey PR, Hansen DD, Wessel DL, Lang P, Jonas RA, Elixson EM. Blunting of stress responses in the pulmonary circulation of infants by fentanyl. Anesth Analg. 1985;64:1137–42
© 2014 International Anesthesia Research Society