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.
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