Markedly long pause due to sinus arrest during dexmedetomidine use and nasal continuous positive airway pressure in two infants with respiratory syncytial virus infection

Published:September 09, 2020DOI:https://doi.org/10.1016/j.jccase.2020.08.012

      Abstract

      Nasal respiratory support for infants with respiratory distress caused by respiratory syncytial (RS) virus infection sometimes requires appropriate sedation. Dexmedetomidine can be an alternative sedative because of its advantage of less frequent respiratory suppression. We report the cases of twin infants with RS virus infection who showed unreported long pauses (4 and 10 s) due to sinus arrest while receiving dexmedetomidine. After termination of dexmedetomidine administration, the long pause of >2 s was no longer observed in both cases. RS virus infection may inhibit the conduction system and sometimes induce bradyarrhythmia. Cardiac and sinus arrests are reported as complications of dexmedetomidine administration. Thus, because dexmedetomidine administration and RS virus infection may additively or synergistically inhibit the conduction system, the use of dexmedetomidine in infantile RS infection should be carefully considered. If sedation is unavoidable, other drugs should be used first. An evidence-based safe regimen for sedation in infants with RS infection should be established in the near future.
      <Learning objective: Dexmedetomidine use as a sedative should be carefully considered in infants with respiratory syncytial (RS) infection because dexmedetomidine administration and RS virus infection may additively or synergistically inhibit the conduction system. If sedation is unavoidable, other drugs should be used first.>

      Keywords

      Introduction

      Respiratory syncytial (RS) virus infection causes bronchiolitis and severe respiratory distress in infants. Recently, nasal respiratory support, such as high-flow nasal cannula and nasal continuous positive airway pressure (nCPAP), has been developed to provide efficient management of such conditions [
      • Vahlkvist S.
      • Jurgensen L.
      • la Cour A.
      • Markoew S.
      • Petersen T.H.
      • Kofoed P.E.
      High flow nasal cannula and continuous positive airway pressure therapy in treatment of viral bronchiolitis: a randomized clinical trial.
      ]. Using the afore-mentioned devices in agitated infants often requires appropriate sedation.
      Dexmedetomidine is an alternative sedative with advantages of less frequent respiratory suppression or hypotension. However, the safety of dexmedetomidine use in patients with RS virus infection remains unclear. We here report the cases of twin infants with RS infection who showed unreported long pauses due to sinus arrest while receiving dexmedetomidine.

      Case report

       Case 1

      A 2-month-old male infant was admitted to another hospital because of coughing, rhinorrhea, and expiratory wheezing due to RS virus infection. He was born at a gestational age of 36 weeks and 6 days, with a birth weight of 2359 g, as twin B of dichorionic diamniotic twins. He was transferred to our center 5 days after symptom onset because of worsening respiratory distress, which was encountered after the long pause in case 2. The plasma creatine kinase (CK) level on admission was within the normal range (115 U/L). We initiated nCPAP with a FiO2 of 0.4. Heart and respiratory rates were 110–130 bpm and approximately 60 breaths/min, respectively. As his tachypnea and retraction worsened on crying, we initiated administration of 0.25 μg/kg/h dexmedetomidine for sedation. The respiratory rate decreased to 30–45 breaths/min. The patient exhibited a 4-s pause caused by sinus arrest after an atrioventricular block of one beat occurred 70 min after dexmedetomidine administration (Fig. 1). Because this episode did not recur, we continued to administer dexmedetomidine to the patient. Subsequently, we increased the dosage to 0.75 μg/kg/h because of persistent irritability. Although his dyspnea gradually ameliorated, cardiac monitoring repeatedly showed sinus bradycardia with a heart rate of <40 bpm, which recovered within a minute on the seventh day of illness. Apnea or decreased peripheral capillary oxygen saturation (SpO2) was not detected before the pause or bradycardia. Echocardiography did not show any structural or functional abnormalities.
      Fig. 1
      Fig. 1Monitor electrocardiography image of case 1 showing a long pause of >4 s. The last arrow indicates an unconducted P wave. After this wave, the pause persisted because of sinus arrest until a junctional escape beat occurred (last beat). Note that the PR intervals seen in first 5 beats were normal. P waves are indicated with red arrows.
      We discontinued dexmedetomidine administration. Thereafter, we did not find a pause of >2 s. Only transient sinus bradycardia with a heart rate of 50–60 bpm was noted until 1 day after discontinuation. We did not find any significant findings in 12-lead electrocardiogram 1 day after cessation of dexmedetomidine (154 bpm of heart rate with sinus rhythm, 100 ms of PR intervals, 73 ms of the QRS duration, and 256 ms of QT interval with 350 ms of QTc with Fridericia correction). Holter electrocardiography signals recorded during the eighth and ninth days of illness did not indicate any bradycardia or bradyarrhythmia. Thereafter, the patient’s respiratory condition and heart rhythm were stable. He was discharged home on the 12th day of illness.

       Case 2

      A 2-month-old female infant, twin A sister of case 1, was transferred to our center on the fifth day of illness with respiratory distress due to RS virus infection. We initiated nCPAP and administration of a small dose (0.25 μg/kg/h) of dexmedetomidine. Heart and respiratory rates before initiating dexmedetomidine administration were 110–130 bpm and approximately 45 breaths/min, respectively. While the respiratory distress gradually improved and respiratory rate decreased to 20–40 breaths/min under 0.5 μg/kg/h of dexmedetomidine administration, we observed mild transient sinus bradycardia (40–60 bpm) and a long pause of a maximum of 10 s due to sinus arrest (Fig. 2) on the 6th day of illness. Apnea or decreased SpO2 was not detected prior to the pause. There were no significant findings in 12-lead electrocardiography during the use of a reduced dose of dexmedetomidine of 0.25 μg/kg/h (187 bpm of heart rate with sinus rhythm, 85 ms of PR intervals, 65 ms of the QRS duration, and 237 ms of QT interval with 346 ms of QTc with Fridericia correction). Echocardiography did not show any structural or functional abnormalities. The plasma CK level on the 7th day of illness was normal (59 U/L).
      Fig. 2
      Fig. 2Monitor electrocardiography image of case 2 showing a markedly long pause of >10 s due to sinus arrest without an escape beat. The QRS waves are indicated with red arrows.
      We did not find a pause of >2 s after discontinuation of dexmedetomidine administration. Only mild transient sinus bradycardia with a heart rate of 50–60 bpm was noted until 2 days after discontinuation. Holter electrocardiography on the 9th and 24th day of illness did not reveal any bradycardia or arrhythmia. She was discharged home on the 15th day of illness.

      Discussion

      The twin infants showed severe unreported long pauses due to sinus arrest while receiving dexmedetomidine for sedation, which was required during nCPAP for respiratory distress due to RS infection. Given their clinical courses, sinus arrest can be attributed to the RS infection, dexmedetomidine use, or both in an additive or synergistic manner.
      Bradycardia during RS infection has been frequently reported, with most cases being due to atrioventricular block. Irreversible complete atrioventricular block has also been reported [
      • Karatza A.A.
      • Kiaffas M.
      • Rammos S.
      Complete heart block complicating the acute phase of respiratory syncytial virus bronchiolitis.
      ]. Although much less frequently, sinus arrest during RS infection has also been reported [
      • Haddad W.
      • Agoudemous M.
      • Basnet S.
      Prolonged sinoatrial block in an infant with respiratory syncytial viral bronchiolitis.
      ]. However, in our literature search, the longest reported pause was of 4 s [
      • Haddad W.
      • Agoudemous M.
      • Basnet S.
      Prolonged sinoatrial block in an infant with respiratory syncytial viral bronchiolitis.
      ]. By contrast, case 2 showed a 10-s pause, which was markedly longer, and thus, far more severe than those previously reported.
      The sinus arrest in the present cases occurred during dexmedetomidine administration at a relatively small dose of 0.25–0.5 μg/kg/h and did not recur after discontinuation of the sedative in either case. Dexmedetomidine has side effects of sinus arrest, atrioventricular block [
      • Takata K.
      • Adachi Y.U.
      • Suzuki K.
      • Obata Y.
      • Sato S.
      • Nishiwaki K.
      Dexmedetomidine-induced atrioventricular block followed by cardiac arrest during atrial pacing: a case report and review of the literature.
      ], and cardiac arrest [
      • Gerlach A.T.
      • Murphy C.V.
      Dexmedetomidine-associated bradycardia progressing to pulseless electrical activity: case report and review of the literature.
      ]. These bradycardic events have been reported to occur irrespective of the dexmedetomidine dose [
      • Takata K.
      • Adachi Y.U.
      • Suzuki K.
      • Obata Y.
      • Sato S.
      • Nishiwaki K.
      Dexmedetomidine-induced atrioventricular block followed by cardiac arrest during atrial pacing: a case report and review of the literature.
      ]. Consistently, severe sinus arrest occurred in both of our cases even with a relatively small dexmedetomidine dose of 0.25–0.5 μg/kg/h. Various circulatory disturbances prior to cardiac arrest during dexmedetomidine use have been reported, including sinus bradycardia, atrioventricular block, and hypotension [
      • Takata K.
      • Adachi Y.U.
      • Suzuki K.
      • Obata Y.
      • Sato S.
      • Nishiwaki K.
      Dexmedetomidine-induced atrioventricular block followed by cardiac arrest during atrial pacing: a case report and review of the literature.
      ,
      • Ozaki M.
      • Takeda J.
      • Tanaka K.
      • Shiokawa Y.
      • Nishi S.
      • Matsuda K.
      • et al.
      Safety and efficacy of dexmedetomidine for long-term sedation in critically ill patients.
      ]. To our knowledge, irreversible cardiac arrest caused by dexmedetomidine use has not been reported previously. Sinus arrest improved several hours after the discontinuation of dexmedetomidine administration [
      • Berkenbosch J.W.
      • Tobias J.D.
      Development of bradycardia during sedation with dexmedetomidine in an infant concurrently receiving digoxin.
      ,
      • Shepard S.M.
      • Tejman-Yarden S.
      • Khanna S.
      • Davis C.K.
      • Batra A.S.
      Dexmedetomidine-related atrial standstill and loss of capture in a pediatric patient after congenital heart surgery.
      ,
      • Hammer G.B.
      • Drover D.R.
      • Cao H.
      • Jackson E.
      • Williams G.D.
      • Ramamoorthy C.
      • et al.
      The effects of dexmedetomidine on cardiac electrophysiology in children.
      ]. The findings in our cases were consistent with those of previous reports. However, only mild transient sinus bradycardia with a heart rate of 50–60 bpm was noted until 1–2 days after discontinuation of dexmedetomidine despite relatively short half-life of the drug of approximately 3 h [
      • Chrysostomou C.
      • Schulman S.R.
      • Herrera Castellanos M.
      • Cofer B.E.
      • Mitra S.
      • da Rocha M.G.
      • et al.
      A phase II/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates.
      ]. This can be explained by two factors: (1) recovery of sinus dysfunction, once occurred, may take some time over the elimination of dexmedetomidine, and (2) the sinus dysfunction was caused not only by dexmedetomidine but by the RS virus infection or other factors in our cases.
      The use of nCPAP may increase the vagal tone [
      • Nelesen R.A.
      • Yu H.
      • Ziegler M.G.
      • Mills P.J.
      • Clausen J.L.
      • Dimsdale J.E.
      Continuous positive airway pressure normalizes cardiac autonomic and hemodynamic responses to a laboratory stressor in apneic patients.
      ]. However, after the cessation of the dexmedetomidine without changing the use of nCPAP, bradyarrhythmias were ameliorated in both cases. Although the use of nCPAP may contribute to the occurrence of bradyarrhythmia, we do not believe that the use of nCPAP was the central cause of the severe pause.
      Taken together, the sinus arrest in the present cases was probably due to the additive or synergistic effect of RS infection and dexmedetomidine use. Only one case of bradycardia during dexmedetomidine use in a patient with RS infection has been reported previously. This patient was a 5-week-old female infant with trisomy 21 and atrioventricular septal defect. Upon receiving digoxin, morphine, and dexmedetomidine (a bolus of 0.5 μg/kg administered for 15 min, followed by an infusion at 0.44 μg/kg/h), sinus bradycardia developed at 40–50 bpm but subsequently recovered after discontinuation of dexmedetomidine administration [
      • Berkenbosch J.W.
      • Tobias J.D.
      Development of bradycardia during sedation with dexmedetomidine in an infant concurrently receiving digoxin.
      ]. By contrast, the present two cases showed a much severe bradyarrhythmia with long pauses (4 and 10 s) due to sinus arrest, although the patients did not have congenital heart disease or risk factors of bradycardia (e.g. digoxin use) other than RS infection. In conclusion, the use of dexmedetomidine in infantile RS infection should be carefully considered along with possible side effects as seen in our cases. If sedation is unavoidable, other drugs should be used first. An evidence-based safe regimen for sedation in infants with RS infection should be established in the near future.

      Declaration of interest

      None.

      Acknowledgments

      We thank all the physicians and medical staff who were involved in the treatment of the infants.

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