Diagnosis of a Supraventricular Tachydysrhythmia During Ketamine Infusion

Authors: Esteban Davila, MD and Ian S. deSouza, MD

Background

Ketamine has many known cardiovascular properties both on the myocardium and the autonomic nervous system through central sympathetic stimulation and inhibition of catecholamine reuptake. The ketamine-induced hyperadrenergic state causes transient elevations in heart rate and blood pressure.[1] We present a case of a possible ketamine-induced, atrioventricular nodal inhibition during procedural analgosedation for electrocardioversion of a supraventricular tachydysrhythmia.

Case

A middle-aged man presented to the ED with one day of palpitations, exertional chest pain, and shortness of breath. His heart rate was 213 beats per minute, blood pressure was 86/61 mm Hg, respiratory rate was 20 breaths per minute, temperature was 98.2 degrees Fahrenheit, and pulse oximetry was 100% on ambient air. The patient was in mild distress with tachycardia, clear chest upon auscultation, and warm extremities. The initial 12-lead ECG is shown below.

Figure 1. The initial ECG shows a regular, narrow QRS complex tachycardia at 211/minute; there are diffuse ST-depressions and reciprocal ST-elevation in aVR suggesting subendocardial ischemia.

While preparing for electrocardioversion, a modified Valsalva maneuver and escalating doses (6 mg, 12 mg, 12 mg) of adenosine proved neither therapeutic nor diagnostic. After 10 minutes during which no other agent was given, the ED team administered ketamine 1.5 mg/kg by slow intravenous push for analgosedation prior to shock delivery and immediately observed the following rhythm change:

Figure 2. During ketamine infusion, there is transient inhibition of atrioventricular nodal conduction, reducing the ventricular rate and revealing atrial flutter waves (F, red arrows) at 240 ms intervals (blue arrows). Note that the defibrillator has been synchronized to the R waves in preparation for direct-current cardioversion.

Electrocardioversion at 100 joules terminated the tachydysrhythmia, and sinus rhythm resumed. Serial troponin measurements were within the normal range. The patient was transferred for definitive therapy, and the electrophysiologist successfully ablated a cavotricuspid, isthmus-dependent atrial flutter.

Discussion

Ketamine has many indications including treatment of refractory depression, general anesthesia, procedural analgosedation, and analgesia.[1] Ketamine is classified as a non-competitive N-methyl-D-aspartate and glutamate receptor antagonist. The antagonism of N-methyl-D-aspartate receptors is responsible for the effects of amnesia, psychosensory changes, analgesia, and neuroprotection.[1] Although ketamine has been shown to have direct negative inotropic effects on the myocardium, it induces a net increase in cardiac output through the potentiation of catecholamines, indirectly activating beta-1 adrenergic receptors on cardiomyocytes.[2]

In the case, intravenous ketamine appears to have inhibited AV nodal conduction to the point of uncovering an underlying, atrial flutter rhythm. Adenosine’s half-life is in the range of seconds, and the 10-minute drug-free interval between the last dose of adenosine and ketamine infusion suggests that pharmacologically, only ketamine could have inhibited AV nodal conduction. In experimental studies, [3,4] relatively small doses of ketamine do not appear to affect AV nodal conduction, however, at larger doses, ketamine has been found to exert negative dromotropic effects.[5]

At typical procedural sedation doses (1 to 2 mg/kg), ketamine has not been previously reported to influence AV nodal conduction, however, there are possible mechanisms. At therapeutic concentrations, ketamine shortens the action potential duration of human atrial myocytes through the inhibition of L-type calcium channels.[6] Ketamine has also demonstrated concentration-dependent inhibition of L-type calcium channels in vascular smooth muscle with evidence of complete action potential blockade at an elevated dose.[7] These L-type calcium channels are expressed in the AV node, and it is through antagonism of these channels that calcium channel blockers decrease AV nodal conduction to reduce the ventricular rate of a supraventricular tachydysrhythmia.[8] Another possible cause of AV nodal inhibition in this case could have been coincidental, autonomic influence from rate-related, myocardial ischemia.[9] However, the ECG suggested only subendocardial ischemia and normal serial troponin measurements excluded myocardial infarction.

Ketamine’s known side effects may offer insight into another potential mechanism for transient AV nodal inhibition. Ketamine can induce nausea and emesis through vestibular system activation by inhibiting serotonin reuptake, thereby indirectly leading to serotonin-receptor 5-HT2 and serotonin-receptor 5-HT3 agonism.[1,10,11] A serotoninergic mechanism for ketamine-related nausea and emesis is further supported by the finding that serotonin-receptor 5-HT3 antagonists when administered concurrently with ketamine may reduce the incidence of emesis.[1,12] Indirect serotonin receptor agonism is one mechanism that activates the nucleus tractus solitarius in the hindbrain. The nucleus tractus solitarius coordinates the emesis response and augments cardiac vagal tone through excitatory projections to vagal motor neurons.[2,13] In the presented case, it is possible that ketamine’s activation of the vestibular system initiated this vagotonic cascade to inhibit AV nodal conduction, while the corresponding symptom of nausea could not be reported, being hidden by ketamine’s dissociative effect.

Conception: Henry Boccon-Gibod

There is significant variation in analgosedative drug selection for procedural sedation prior to electrocardioversion,[14,15] and ketamine is rarely chosen for this indication,[14,15] perhaps being counterintuitive in the setting of tachydysrhythmia. However, this case suggests an additional, previously unreported effect of transient AV nodal inhibition associated with ketamine. When given during an undifferentiated, supraventricular tachydysrhythmia, ketamine may help diagnose an atrial tachydysrhythmia (such as atrial flutter or atrial tachycardia) or potentially terminate a reentrant tachydysrhythmia whose pathway involves the AV node (such as atrioventricular nodal reentrant tachycardia). This possible effect on AV nodal conduction may prompt clinicians to preferentially select ketamine for analgosedation when performing electrocardioversion of an undifferentiated, unstable supraventricular tachydysrhythmia.