Cardiorespiratory arrest in a healthy volunteer after a single oral dose of 80 mg of the beta-blocker propranolol

Abstract

The oral administration of a single low-to-moderate dose ofpropranolol(30–80 mg)inyounghealthyvolunteersis widelyusedto probe the brain’s (nor)adrenergic system (for example as pub-lishedinNLM:Oei,Tollenaar,Elzinga,STollenaar,Elzinga, Spinhoven, & Everaerd, 2009; Van Stegeren et al., 2007).Propranolol, a beta-adrenergic antagonist, is an effective tool forinvestigatingtheroleofthebeta-adrenergicsysteminpsychologicalprocesses of interest. It is typically used in a placebo-controlleddesigntoparceloutthecontributionofthebeta-adrenergicsystem.The common side effects of propranolol, a drop in pulse rate andblood pressure, are well known and typically well endured. How-ever, it is less known that in rare cases the oral administration of asingle dose of propranolol may induce cardiorespiratory arrest inhealthy young volunteers.We describe a case of a young healthy volunteer without anyknown pre-existing medical condition, who participated in achallenge study and suffered a non-fatal cardiac arrest after oraladministrationofasingledoseof80 mgpropranolol.Weusedadou-ble-blind pseudo-randomized placebo-controlled crossover designof two consecutive days to investigate the effect of modulation ofthebeta-adrenergicsystemondifferentcomponentsoftheEEGpat-tern. The protocol was approved by the Medical Ethical CommitteeoftheLeidenUniversityMedicalCenterandsubjectsgavewrittenin-formed consent. A blood pressure in rest below 100/60 mmHg or apulse rate of less than 60 beats per minute (BPM) were exclusioncriteria for the study. The study was performed in the DepartmentofPsychologyofLeidenUniversity.Basedonpriorextensiveexperi-encewiththisparadigm(Oeietal.,2010;Tollenaaretal.,2009;VanStegerenetal.,2007)andadvicefrominternists,onlyaphysicianoncall with knowledge of the protocol was deemed necessary.The healthy volunteer was an eighteen-year-old male student,who was the last of the 20 subjects scheduled to participate in ourexperiment. He had no past or current history of cardiac, pulmonaryor other physical diseases. There had been no prior exposure to abeta-blocker.Thefamilyhistorymentionedthedeathofagrandfatherattheageof45,possiblyduetoacardiacarrest.Theothergrandfatherhad cardiac valve surgery at older age. The volunteer was an activesportsman.Hewasmemberofarowingcompetitionteamandtrainedfour times a week and he also played football. He was a non-smokerandusednodrugs.Heused2unitsofalcoholperday.Routinephysicalexamination showed no neurological, cardiac or pulmonary abnor-malities. The subject had a blood pressure of 120/65 mmHg with aregular pulse rate of 60 BPM while sitting, and a tension of 120/70 mmHg witha pulse rate of65 BPM while standing.The volunteer arrived in the morning of the first test day. Bloodpressure at baseline was 140/69 mmHg, with a pulse rate of 63BPM. The volunteer received an oral dose of 80 mg propranolol(blinding was broken on his test day). Thirty minutes after baselinethe blood pressure was 141/64 mmHg, with a pulse rate of 49 BPM.The volunteer felt as usual and was e-mailing. Subsequently, hewas accompanied to and placed in the EEG set-up. The volunteercomplained of being hungry and hot, and then collapsed. Hestopped breathing and there were convulsions. The researchersimmediately called an ambulance as well as the physician on call.Meanwhile the volunteer had already regained consciousness andhad a blood pressure of 110/65 with a pulse rate of 50 BPM. Afterarrival of the emergency personnel and the physician, ECG moni-toring was started and atropine administered intravenously. How-ever, the volunteer collapsed again and stopped breathing, andthere was a short asystolic period, ended by a precordial thump.He almost immediately regained consciousness again. After intra-venous administration of more atropine and physiological saltthe bradycardia disappeared and the blood pressure rose. The vol-unteer was transferred to the cardiology department for furtherobservation and evaluation. Both echography and 24-h ECG re-vealed no abnormalities. The cardiologist’s conclusion was cardio-respiratory arrest due to propranolol. The following day thevolunteer was discharged in good condition, without the need forany further follow-up.Therearemanyreportsintheliteratureoncardiorespiratoryarrestafteroraladministrationofpropranololincardiopulmonarycompro-misedpatientsorinthecaseofanoverdose. We could, however,notidentify any recent reports of cardiorespiratory arrest in healthyyoungvolunteersafteroraladministrationofasingledoseofpropran-olol. Our case report indicates that besides careful screening ofhealthy subjects in experiments involving the oral administration ofa single dose of propranolol, it is also necessary to have trained staffandequipment for resuscitation available atthe testsite.References