Dexmedetomidine and Cardiac Arrest
Ingersoll-Weng, Esperanza M.D.*; Manecke, Gerard R. Jr., M.D.†; Thistlethwaite, Patricia A. M.D., Ph.D.‡
DEXMEDETOMIDINE is an α-2 receptor agonist often administered to surgical patients because of its sedative, analgesic, and anxiolytic properties. Although severe bradycardia is a known adverse effect, bradycardia leading to asystole in the clinical setting has yet to be reported. We report a case of cardiac arrest in a patient receiving a dexmedetomidine infusion as a supplement to general anesthesia.
A 52-yr-old 60-kg woman with myasthenia gravis presented for thymectomy and excisional biopsy of a right lung mass via median sternotomy. A preoperative chest computed tomography revealed an anterior mediastinal mass suggestive of thymoma and two small right lower lobe densities. She was otherwise healthy and exercised vigorously 3 to 4 times per week. Her myasthenia, diagnosed 2 months previously, caused mild symptoms, including occasional diplopia and mild upper extremity weakness. These symptoms resolved only partially with the use of pyridostigmine, 120 mg orally three times daily. The patient’s preoperative pulmonary function tests were normal, and her preoperative electrocardiogram exhibited normal sinus rhythm at 60 beats per minute.
On the day of surgery, the patient took her morning pyridostigmine dose. After placement of an IV catheter, she was taken to the operating room, where routine monitors were applied. Initial vital signs were: blood pressure, 130/65; heart rate, 78 beats per minute; and oxygen saturation, 100%. She received midazolam intravenously in 2-mg increments while a thoracic epidural (T6–7) was placed. The epidural, placed solely for postoperative pain relief, was tested with 3 ml lidocaine, 2%, with 150 μg epinephrine. This test dose resulted in a small thoracic band of anesthesia with no change in heart rate, blood pressure, or motor function. No further medications were administered via the epidural catheter during operative period. At the conclusion of epidural placement, the patient had received a total of 10 mg midazolam and was still fully alert and anxious. Her vital signs at that time were blood pressure, 133/72; heart rate, 75 beats per minute; and oxygen saturation, 100%. After placement of a radial arterial catheter, a loading dose of 1 μg/kg dexmedetomidine was given over 10 min, followed by an infusion at 0.2 μg/kg/h. The patient initially exhibited a transient increase in blood pressure (145/78), and her heart rate decreased to 48 beats per minute.
General anesthesia was induced with 250 μg fentanyl, and 200 mg propofol intravenously. No neuromuscular blockade was used. The patient’s vital signs remained stable through induction and laryngoscopy, with heart rate 46–50 beats per minute. Anesthesia was maintained with isoflurane, 0.7–0.9%, in 100% oxygen and the dexmedetomidine infusion. The patient remained stable through the start of surgery with blood pressure 100–105/50–55. On sternal retraction, the patient’s heart rate dropped into the 30s and 0.5 mg atropine was given. Asystole soon followed, at which time she received open cardiac massage and 300 μg IV epinephrine. There was prompt return of the blood pressure and the asystole episode lasted less than 2 min. The dexmedetomidine infusion was discontinued and the remainder of the surgery proceeded uneventfully, with the patient’s blood pressure ranging from 100–110 to 50–60, and her heart rate 50–60 beats per minute. She was awakened at the conclusion of surgery and the trachea was extubated. There was no evidence of neurologic compromise. The patient was discharged to home on the fourth postoperative day.
Dexmedetomidine is an α-2 adrenergic receptor agonist with sedative, analgesic, and anxiolytic properties. It has a selectivity for α-2 receptors eightfold greater than clonidine, and it is considered a full agonist at the α-2 adrenergic receptor. 1
Dexmedetomidine has been shown to decrease opioid and inhaled anesthetic requirements, making it an attractive adjunct to general anesthesia. 2,3
When administered to healthy volunteers, dexmedetomidine causes a dose-dependent decrease in blood pressure and heart rate but does not demonstrate clinically relevant respiratory depression, despite its profound sedative effects. 4,5
Its sympatholytic properties, in conjunction with its anesthetic actions, make it an attractive choice for coronary artery surgery 6,7
as well as other major operations. 7–10
Dexmedetomidine has been observed to display a biphasic arterial blood pressure response, causing transient increase in pressure followed by a sustained decrease. The observed heart rate response seems to be a combination of a baroreflex-mediated reduction in heart rate, coinciding with the transient increase in blood pressure, centrally mediated reduced sympathetic tone, and increased vagal tone. 1,4
Severe bradycardia following administration of α-2 agonists is well documented. 1,11,12
To our knowledge, however, this is the first reported clinical case of asystole related to the use of dexmedetomidine. A number of factors may have contributed to the development of asystole in this patient. We believe a centrally mediated decrease in sympathetic outflow and increase in parasympathetic outflow resulting from dexmedetomidine, as well as the patient’s autonomic response to abrupt surgical stimulation, were the primary contributors. The bradycardic response observed with dexmedetomidine can be augmented by the concurrent use of other medications with negative chronotropic and/or vagal effects. For example, significant bradycardia was observed in a 5-week-old infant treated with digoxin during sedation with dexmedetomidine. 13
In our case, the patient was being treated with pyridostigmine, which increases vagal tone. Pyridostigmine, an anticholinesterase used for the symptomatic treatment of myasthenia gravis, increases the concentration of acetylcholine at muscarinic and nicotinic receptors. The activation of cardiac muscarinic receptors accounts for the drug’s negative chronotropic effect, which is exacerbated by the concomitant administration of other negative chronotropes such as digitalis, calcium channel blockers, and beta blockers. 14
Pyridostigmine is known to antagonize and may also potentiate neuromuscular blockers; however, it has no reported interactions with other often used anesthetic agents. 15
Although it is unclear whether the pyridostigmine had any significant cardiovascular effects on this patient, it may have interacted with dexmedetomidine in an additive or synergistic fashion.
This patient likely had increased vagal tone at baseline, given her level of physical activity and low resting heart rate. Bloor et al.1
also noted bradydysrhythmia in three patients within minutes of dexmedetomidine infusion, when the plasma concentration of dexmedetomidine is presumably high. Their study involved healthy young men with low resting heart rates. These events were associated with increased blood pressure, and Bloor et al.
attributed them to reflex-mediated slowing secondary to peripheral hypertensive response. In our patient, the severe bradycardia progressing to asystole coincided temporally with the sternotomy and sternal retraction. This surgical stimulus may have produced a vaso-vagal response, which led to cardiac standstill. Another possibility is that, on sternal retraction, mechanosensory receptors in the heart were stimulated, resulting in the Bezold-Jarisch reflex. This reflex, mediated by vagal efferents and decreased sympathetic vasomotor tone, may cause severe bradycardia and hypotension. 16
The patient was given a modest dose of fentanyl prior to induction of anesthesia. Dexmedetomidine has been shown to reduce opioid requirements as well as augment the bradycardia that may be observed with their use. 2,17
Another possible, but unlikely, factor in this case is the epidural. As mentioned previously, the epidural was placed to provide only postoperative pain relief, and except for the test dose, no other medications were administered epidurally during surgery. Bradycardia and cardiac arrest are well-documented complications of spinal and epidural anesthesia. 18–22
However, although the small epidural test dose could have caused a modest amount of sympatholysis, an hour had elapsed between the placement and testing of the epidural and the episode of asystole. This argues against sympatholysis from the epidural playing a significant role in this event.
In summary, we report a case of severe bradycardia progressing to asystole in a patient receiving a dexmedetomidine infusion to supplement general anesthesia. The prompt and effective treatment of this event resulted in complete recovery with no evidence of cardiovascular or neurologic compromise. Several factors combined to cause asystole in this patient, and caution must be exercised when administering dexmedetomidine in the presence of other negative chronotropic influences.
1. Bloor BC, Ward DS, Belleville JP, Maze M: Effects of intravenous dexmedetomidine in humans: II. Hemodynamic changes A nesthesiology 1992; 77: 1134–42
2. Salmenpera MT, Szlam F, Hug CC: Anesthetic and hemodynamic interactions of dexmedetomidine and fentanyl in dogs. A nesthesiology 1994; 80: 837–46
3. Khan ZP, Munday IT, Jones RM, Thornton C, Mant TG, Amin D: Effects of dexmedetomidine on isoflurane requirements in healthy volunteers: Pharmacodynamic and pharmacokinetic interactions. Br J Anaesth 1999; 83: 372–80
4. Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD: The effects of increasing plasma concentrations of dexmedetomidine in humans. A nesthesiology 2000; 93: 382–94
5. Belleville JP, Ward DS, Bloor BC, Maza M: Effects of intravenous dexmedetomidine in humans: I. Sedation, ventilation, and metabolic rate. A nesthesiolgy 1992; 77: 1125–33
6. Jaionen J, Hynynen M, Kuitunen A, Heikkila H, Perttila J, Salmenpera M, Valtonen M, Aantaa R, Kallio A: Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. A nesthesiology 1997; 86: 331–45
7. Wijeysundera DN, Naik JS, Beattie WS: Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: A meta-analysis. Am J Med 2003; 114: 742–52
8. Talke P, Li J, Jain U, Leung J, Drasner K, Hollenberg M, Mangano DT: Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. A nesthesiology 1995; 82: 620–33
9. Aho M, Lehtinen AM, Erkola O, Kallio A, Korttila K: The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy. A nesthesiology 1991; 74: 997–1002
10. Aho M, Erkola O, Kallio A, Scheinin H, Korttila K: Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy. Anesth Analg 1992; 75: 940–6
11. Erkola O, Korttila K, Aho M, Haasio J, Aantaa R, Kallio A: Comparison of intramuscular dexmedetomidine and midazolam premedication for elective abdominal hysterectomy. Anesth Analg 1994; 79: 646–53
12. Talke P, Chen R, Thomas B, Aggarwall A, Gottlieb A, Thorborg P, Heard S, Cheung A, Son SL, Kallio A: The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg 2000; 90: 834–9
13. Berkenbosch JW, Tobias JD: Development of bradycardia during sedation with dexmedetomidine in an infant concurrently receiving digoxin. Pediatr Crit Care Med 2003; 4: 203–5
14. Arsura EL, Brunner NG, Namba T, Grob D: Adverse Cardiovascular effects of anticholinesterase medications. Am J Med Sci 1987; 293: 18–23
15. Keeler JR: Interactions between nerve agent pretreatment and drugs commonly used in combat anesthesia. Mil Med 1990; 155: 527–33
16. Campagna JA, Carter C: Clinical relevance of the Bezold-Jarisch reflex. A nesthesiology 2003; 98: 1250–60
17. Aho MS, Erkola OA, Scheinin H, Lehtinen AM, Korttila KT: Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation. Anesth Analg 1991; 73: 112–8
18. Caplan RA, Ward RJ, Posner K, Cheney FW: Unexpected cardiac arrest during spinal anesthesia: A closed claims analysis of predisposing factors. A nesthesiology 1988; 68: 5–11
19. Gild W, Crilley P: Sudden cardiac arrest during epidural anesthesia (letter). A nesthesiology 1990; 73: 1296
20. Chan KK, Welch KJ: Cardiac arrest during segmental thoracic epidural anesthesia. A nesthesiology 1997; 86: 503–5
21. Palmer SK: What is the incidence of arrest and near arrest during spinal and epidural analgesia? Report of nine years experience in an academic group practice (abstract). Anesth Analg 2001; 92: S339
22. Pollard JB: Common mechanisms and strategies for prevention and treatment of cardiac arrest during epidural anesthesia. J Clin Anesth 2002; 14: 52–6
This article has been cited 36 time(s).
Critical CareCan dexmedetomidine be a safe and efficacious sedative agent in post-cardiac surgery patients? a meta-analysisCritical Care
Annales Francaises D Anesthesie Et De ReanimationDexmedetomidine and clonidine: A review of their pharmacodynamy to define their role for sedation in intensive care patientsAnnales Francaises D Anesthesie Et De Reanimation
Pediatric CardiologyDexmedetomidine: Antiarrhythmic Effects in the Pediatric Cardiac PatientPediatric Cardiology
Pediatric AnesthesiaPain, fentanyl consumption, and delirium in adolescents after scoliosis surgery: dexmedetomidine vs midazolamPediatric Anesthesia
AnaesthesiaA randomised controlled trial of dexmedetomidine for suspension laryngoscopyAnaesthesia
Pediatric AnesthesiaSevere hypertension and bradycardia after dexmedetomidine for radiology sedation in a patient with acute transverse myelitisPediatric Anesthesia
Anesthesia and AnalgesiaDexmedetomidine Sedation (and Cardiac Perforation, Pericardial Tamponade, Cardiac Arrest, and Cardiopulmonary Resuscitation) Leading to Refractory Cardiogenic ShockAnesthesia and Analgesia
Pediatric CardiologyUse of dexmedetomidine in patients with trisomy 21 after cardiac surgeryPediatric Cardiology
Annals of PharmacotherapyAn Updated Focused Review of Dexmedetomidine in AdultsAnnals of Pharmacotherapy
Journal of Clinical AnesthesiaDexmedetomidine suppresses the decrease in blood pressure during anesthetic induction and blunts the cardiovascular response to tracheal intubationJournal of Clinical Anesthesia
Journal of Clinical AnesthesiaComparison of patient-controlled analgesia with and without dexmedetomidine following spine surgery in childrenJournal of Clinical Anesthesia
Anesthesia and AnalgesiaCaution Is Necessary When Dexmedetomidine Is Used Off-Label, Especially When Combined with Other SedativesAnesthesia and Analgesia
Journal of AnesthesiaBuccal administration of dexmedetomidine as a preanesthetic in childrenJournal of Anesthesia
Pediatric AnesthesiaA combination of ketamine and dexmedetomidine sedation with caudal anesthesia during incarcerated inguinal hernia repair in three high-risk infantsPediatric Anesthesia
Annals of PharmacotherapyDexmedetomidine: An updated reviewAnnals of Pharmacotherapy
Pace-Pacing and Clinical Electrophysiology
Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale
Pace-Pacing and Clinical Electrophysiology, 30(9):
Pediatric AnesthesiaHemodynamic effects of dexmedetomidine sedation for CT imaging studiesPediatric Anesthesia
Anesthesia and AnalgesiaThe effects of centrally administered dexmedetomidine on cardiovascular and sympathetic function in conscious ratsAnesthesia and Analgesia
Anesthesia and AnalgesiaDexmedetomidine for pediatric sedation for computed tomography imaging studiesAnesthesia and Analgesia
Anesthesia and AnalgesiaDexmedetomidine infusion during laparoscopic bariatric surgery: The effect on recovery outcome variablesAnesthesia and Analgesia
Pediatric AnesthesiaHemodynamic and respiratory changes following dexmedetomidine administration during general anesthesia: sevoflurane vs desfluranePediatric Anesthesia
Anesthesia and AnalgesiaDexmedetomidine sedation leading to refractory cardiogenic shockAnesthesia and Analgesia
Journal of Clinical AnesthesiaBradycardia leading to asystole during dexmedetomidine infusion in an 18 year-old double-lung transplant recipientJournal of Clinical Anesthesia
Pediatric AnesthesiaSedation trends in the 21st century: the transition to dexmedetomidine for radiological imaging studiesPediatric Anesthesia
Pediatric RadiologyThe pediatric sedation service: who is appropriate to sedate, which medications should I use, who should prescribe the drugs, how do I bill?Pediatric Radiology
American Journal of Health-System PharmacySedation and analgesia in the intensive care unit: Evaluating the role of dexrmedetomidineAmerican Journal of Health-System Pharmacy
Pediatric AnesthesiaDextmedetomidine for pediatric MRI sedation: a review of a series of casesPediatric Anesthesia
PharmacologyEffects of Different Loading Doses of Dexmedetomidine on Bispectral Index under Stepwise Propofol Target-Controlled InfusionPharmacology
AnesthesiologyDexmedetomidine and AsystoleAnesthesiology
AnesthesiologyDexmedetomidine and AsystoleAnesthesiology
Pediatric Critical Care MedicineDexmedetomidine: Do we know enough?*Pediatric Critical Care Medicine
European Journal of Anaesthesiology (EJA)The effect of dexmedetomidine sedation on brachial plexus block in patients with end-stage renal diseaseEuropean Journal of Anaesthesiology (EJA)
Pediatric Critical Care MedicineDexmedetomidine: Applications in pediatric critical care and pediatric anesthesiologyPediatric Critical Care Medicine
American Journal of TherapeuticsPreliminary Experience With Dexmedetomidine for Monitored Anesthesia Care During ENT Surgical ProceduresAmerican Journal of Therapeutics
© 2004 American Society of Anesthesiologists, Inc.
Publication of an advertisement in Anesthesiology Online does not constitute endorsement by the American Society of Anesthesiologists, Inc. or Lippincott Williams & Wilkins, Inc. of the product or service being advertised.