Anesthetic Management of a Patient With Catecholaminergic Polymorphic Ventricular Tachycardia

Abstract

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmogenic disorder induced by adrenergic stress. Electrophysiologically, it is characterized by emotional stress- or exercise-induced bidirectional ventricular tachycardia that may result in cardiac arrest. Minimizing perioperative stress is critical as it can reduce fatal arrhythmias in patients with CPVT. Dexmedetomidine (DEX), a centrally acting sympatholytic anesthetic agent, was used in the successful intravenous (IV) moderate sedation of a 27-year-old female patient with CPVT, a history of cardiac events, and significant dental fear and anxiety scheduled to undergo mandibular left third molar extraction. Oral surgery was successfully performed under DEX-based IV sedation to reduce stress, and no arrhythmias were observed. IV sedation with DEX provided a sympatholytic effect with respiratory and cardiovascular stability in this patient with CPVT who underwent oral surgery.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inheritable arrhythmogenic disorder characterized by physical or emotional stress-induced polymorphic ventricular tachyarrhythmias or bidirectional ventricular tachycardia without any detectable morphological cardiac abnormalities.^1–3 CPVT is a common cause of sudden cardiac death in young otherwise healthy patients, with cardiac events being induced by sympathetic activation and catecholamine release during physical and emotional stress.³ Syncope is the most frequent symptom and often leads to a misdiagnosis of epilepsy.² It is frequently difficult to establish a timely and accurate diagnosis due to normal cardiac imaging, unremarkable baseline electrocardiograms (ECGs), and commonly misattributed syncopal episodes. Early and prompt recognition of CPVT is critical due to its high mortality rate (up to 50%) in severely affected untreated patients by the age of 20 years.² Mutations in the RYR2 gene encoding cardiac ryanodine receptor calcium ion release channels are the leading causes of CPVT.^4,5

Regarding the anesthetic management of patients with CPVT, active measures are needed to reduce stress and anxiety throughout the perioperative period. Because invasive dental procedures, including oral surgery, can induce emotional stress, these patients require sedation or general anesthesia. Dexmedetomidine (DEX) is a highly selective centrally acting α2-adrenoceptor agonist that has 8 times greater specificity for α2 receptors than clonidine.⁶ DEX exerts antihypertensive, analgesic, and sedative effects by inhibiting endogenous catecholamine release at adrenoreceptors located on the substantia gelatinosa of the spinal cord and the locus coeruleus of the brain.^6,7 DEX is often administered in surgical procedures requiring intravenous (IV) sedation,^8,9 as well as in the intensive care unit and is thought to have less respiratory depression than other sedatives.^10,11 However, airway obstruction and apnea with DEX has been noted in several studies.^12,13 It also reduces catecholamine secretion, thereby reducing stress and modestly decreasing heart rate (HR) and blood pressure (BP).⁶ Therefore, the centrally acting sympatholytic effects of DEX could be useful in patients with adrenergic-dependent syndromes, including CPVT. We describe the anesthetic management protocol for DEX-based IV sedation of a patient with CPVT, dental anxiety, and a history of cardiac events. Informed consent to publish case details was obtained from the patient.

CASE PRESENTATION

The patient was a 27-year-old woman (height, 152 cm; weight, 45 kg; body mass index, 19.5 kg/m²) with a significant cardiac history. At 7 and 8 years of age, she experienced exercise-induced syncope. Because her resting ECG excluded long QT and Brugada syndrome and there was no structural heart disease evident per an echocardiogram, CPVT was suspected. Subsequent genetic testing identified a de novo RYR2 mutation that confirmed the CPVT diagnosis, and oral β-blocker administration was started immediately. The cardiologist recommended limiting vigorous physical activity, avoiding dehydration, and reducing anxiety-provoking situations. However, at 22 years of age she experienced emotional stress-induced syncope and regained consciousness while being transported in the ambulance. She had another episode of emotional stress-induced syncope at age 25, and the ECG obtained by paramedics on the scene showed ventricular tachycardia. She was transported to the local hospital where her rhythm was stabilized with IV β-blockers, and she was discharged on the following day.

The patient was scheduled to undergo mandibular left third molar extraction at our dental hospital; however, she expressed significant dental fear and anxiety. Considering her medical history and dental phobia, performing the surgical procedure under local anesthesia posed significant risk for cardiac events, including fatal arrhythmia. After discussion with the treating oral surgeon, the decision was made to treat her using IV moderate sedation (as assessed using the Observer's Assessment of Alertness/Sedation (OAA/S) scale for a target score of 3) to avoid endogenous catecholamine surges secondary to fear/anxiety or inadequate anesthesia.

The preoperative evaluation revealed a BP and HR of 107/47 mm Hg and 57 bpm, respectively. Her percutaneous oxygen saturation (SpO₂) was 97% on room air. No abnormalities were detected on routine preoperative ECG and blood tests, which consisted of a complete blood cell count, serum chemistry panel, and coagulation profile. Examination revealed a Mallampati class I airway. She reported taking nadolol 60 mg and flecainide 150 mg daily. She denied any family history of sudden cardiac or neonatal death and did not have an implantable cardioverter defibrillator (ICD).

On the day of the surgery, the patient presented to the dental hospital appropriately NPO (6 hours fasting; 2 hours no clear fluids) and took her usual morning dose of nadolol and flecainide. To prevent venipuncture stress-induced arrhythmia, a lidocaine patch (Penles Tape 18 mg, Nitto Denko Corporation) was applied to the IV site 30 minutes before she entered the operating room appearing anxious. American Society of Anesthesiologists monitors were placed, consisting of a pulse oximeter, 3-lead ECG, and a noninvasive BP cuff. Her initial vital signs were as follows: BP 105/61 mm Hg; HR 55 bpm; and SpO₂ 98% on room air.

Oxygen 3 L/min was administered via nasal cannula. IV access was secured using a 22-gauge catheter placed in her left hand, and midazolam 2 mg was subsequently administered followed by DEX 6 mcg/kg/h continuous infusion. Her OAA/S score was 4 after 5 minutes with a BP, HR, and SpO₂ of 131/69 mm Hg, 47 bpm, and 100%, respectively. After 10 minutes, her OAA/S score decreased to 3 with a BP, HR, and SpO₂ of 131/68 mm Hg, 46 bpm, and 100%, respectively. The DEX infusion was then reduced to 0.4 mcg/kg/h with her respiratory status being stable, and the oral retractor was placed. Fifteen minutes following the start of sedation, additional midazolam 0.5 mg was administered followed by a left inferior alveolar nerve block using 2 mL of 0.75% ropivacaine (15 mg). An additional 3.6 mL of 3% mepivacaine (108 mg) was administered into the left posterior mandibular buccal gingiva.

The surgical procedure began 25 minutes following sedation initiation with her BP, HR, and SpO₂ being 117/64 mm Hg, 53 bpm, and 100%, respectively. Additional midazolam 0.5 mg was administered 35 minutes after initiating sedation. The patient did not complain of pain during the extraction as her OAA/S score remained at 3. During the operation, spontaneous respirations were maintained, and her mean arterial pressure ranged from 76 to 85 mm Hg, HR ranged from 49 to 56 bpm, and SpO₂ ranged from 99% to 100%. The DEX 0.4 mcg/kg/h infusion was discontinued upon surgery completion, and acetaminophen 1000 mg was also administered intravenously for postoperative analgesia. Total doses were midazolam 3 mg and DEX 56 mcg. Surgery time and sedation duration were 25 and 50 minutes, respectively. The patient remained calm until discharge ∼90 minutes after completing surgery. She was fully awake and ambulatory at discharge and had no complications in the immediate postoperative period. The patient returned the next day for follow-up and expressed being satisfied with the sedation; moreover, she had no recall.

DISCUSSION

This case report demonstrated successful DEX-based IV sedation for dental extractions in a patient with CPVT. This protocol provided adequate intraoperative sedation for anxiety and stress reduction and prevented CPVT-induced fatal arrhythmias.

CPVT is a rare genetically inherited disorder characterized by syncope, arrhythmias, and potentially sudden death occurring during exercise or stress in children and young adults with morphologically normal hearts and normal baseline ECGs.^1–3 CPVT has an estimated prevalence of 1:10,000.² The disease typically presents as a history of syncope with physical exertion or acute emotional stress and has a reported median age of symptom onset of 10.8 years.¹⁴ Syncope can lead to a misdiagnosis of epilepsy.¹⁵ A family history of syncope or sudden death is positive in up to 30% of patients with CPVT.¹⁶ Diagnosis of CPVT is based on the patient's history, exercise stress testing, and genetic testing. ECGs usually appear normal, and the CPVT diagnosis may be missed if an exercise stress test is not performed.²

In 2001, Priori et al⁴ discovered that RYR2 mutations underlie most CPVT cases, as this gene encodes proteins involved with the release of calcium from the sarcoplasmic reticulum and is rendered dysfunctional upon mutation. Fatal arrhythmias can be induced by the resulting imbalance in calcium ion concentration.^17,18 Bidirectional ventricular tachycardia may be triggered by delayed afterdepolarizations secondary to calcium overload.

Medical management of CPVT remains challenging. β-blockers reduce CPVT-induced ventricular arrhythmias and are indicated as a first-line treatment for symptom relief and prevention of sudden cardiac death. However, nonadherence and treatment failure usually occur.^19,20 Nadolol is often preferred due to its prolonged half-life.² Currently, the combined use of flecainide and β-blockers is considered superior to β-blocker monotherapy for reducing the risk of arrhythmic and symptomatic events, especially in patients with genetic mutations.²¹ An ICD may be necessary for patients with recurrent life-threatening arrhythmias or episodes of cardiac arrest.²² A recent multicenter study demonstrated the benefit of left cardiac sympathetic denervation in patients with CPVT.²³ There is currently no treatment that is completely effective or without risks. Moreover, cardiac and fatal or near-fatal events are often observed during long-term follow-up. In an analysis of 101 patients with CPVT with a mean follow-up of 7.9 years, Hayashi et al³ reported cardiac events in 27 patients (27%), including 13 patients (13%) with fatal or near-fatal events. Because CPVT is epinephrine dependent, patients are instructed to abstain from competitive athletics and activities requiring physical exertion as well as to avoid emotional stress.

Anesthetic management, including IV sedation or general anesthesia, is required during oral surgery in patients with CPVT because stress- or anxiety-induced endogenous catecholamine release could cause ventricular arrhythmias or sudden cardiac death. However, few studies have reported IV sedation in patients with CPVT. We developed the anesthetic plan for this patient based on the following considerations: (1) avoiding endogenous catecholamine surges secondary to fear or inadequate levels of anesthesia and analgesia; (2) avoiding extrinsic catecholamines, especially β-adrenergic agonists; and (3) preparing to acutely manage ventricular tachycardia during the perioperative period. Anesthetics often used to manage patients with CPVT include sevoflurane, midazolam, propofol, fentanyl, and remifentanil.^24,25 Ketamine should be avoided because it stimulates sympathetic nervous system activity.

In order to avoid perioperative tachycardia, β-blocker therapy should be continued.²⁶ There have been reports of cardiac events following a missed β-blocker dose.^2,3 Moreover, the patient's usual β-blocker regimen may require supplementation, such as with short-acting IV β-blockers.²⁷ Esmolol, an ultra-short-acting cardioselective β1-adrenergic antagonist, attenuates hemodynamic responses to perioperative noxious stimuli.^28,29 However, its calculated dose should be reduced in the presence of underlying β-blockers. Therefore, IV β-blocker administration should be carefully considered. DEX, a novel α2-adrenergic agonist, exerts anxiolytic, sedative, analgesic, and sympatholytic effects with less respiratory depression than other sedatives.^6,7 DEX and esmolol have different pharmacokinetic profiles. Esmolol is a water-soluble agent that cannot pass through the blood-brain barrier and likely does not involve central β-receptors.³⁰ Contrastingly, DEX is a centrally acting sympatholytic agent that attenuates the stress response.³¹ Central-acting α2-agonists attenuate HR, BP, and plasma catecholamine responses to sympathetic stimulation. Previous studies have shown that the α2-agonist clonidine is more effective in suppressing the sympathetic-mediated increase in plasma catecholamines than esmolol.^32,33 Therefore, we considered that the centrally acting sympatholytic effect of DEX could be more appropriate for adrenergic-dependent syndromes, including CPVT.

The level of consciousness during clinical DEX-based IV sedation is similar to that of natural sleep, wherein patients are easily arousable to stimulation. Therefore, sedating a patient with dental anxiety using DEX alone would likely be insufficient, possibly requiring another sedative. Moreover, it should be noted that IV DEX produces a biphasic BP response: an initial mean arterial pressure increase and HR decrease, followed by a decrease in both. Potential DEX side effects include transient hypertension, hypotension, and bradycardia.⁷ Most patients with CPVT routinely use β-blockers; therefore, careful HR monitoring is required during perioperative DEX administration. Because β-agonists (ie, epinephrine) may induce fatal arrhythmias in patients with CPVT, bradycardia should be treated with atropine. Propofol can attenuate the HR response to IV atropine,³⁴ so a combination of DEX and midazolam was used for IV sedation. A continuous low-dose DEX infusion was used because a high-dose DEX bolus can cause hypotension, bradycardia, and soft tissue airway obstruction.³⁵ Furthermore, anxiety-induced endogenous catecholamine release could have occurred before the DEX effect, so we consequently administered IV midazolam immediately after establishing IV access. Our patient's HR decreased from 55 to 46 bpm as an effect of the initial DEX dose. However, there was a gradual increase in the basal BP (105/61 mm Hg) until it reached its highest intraoperative value (131/68 mm Hg). We observed a biphasic hemodynamic response during DEX loading, and her BP returned to baseline levels. Because our patient remained hemodynamically stable, no atropine was given.

DEX is considered to cause less upper airway obstruction than propofol; however, a recent study by Lodenius et al¹³ showed that at comparable levels of minimal to moderate sedation, DEX and propofol exhibited similar degrees of pharyngeal collapsibility and reductions in ventilatory drive. Spontaneous respirations and airway patency were maintained in our patient as the OAA/S score remained at 3. This suggests that in clinical situations requiring analgesia as well as sedation, the analgesic effect of DEX may allow lighter sedation than propofol and therefore less adverse ventilatory effects. In addition, sedatives like DEX and midazolam act synergistically, which allow dose reductions of each agent when used concomitantly.³⁶ In this case, the DEX and midazolam combination achieved an adequate sedative effect with stable respiratory and cardiovascular states.

Ensuring optimal perioperative analgesia is important in managing patients with CPVT. In patients with familial ventricular arrhythmias, dysrhythmias could be provoked by venipuncture pain.³⁷ A commercially available lidocaine patch is often used for topical anesthesia prior to venipuncture.³⁸ Because our patient did not report pain associated with vascular access, we believe that the lidocaine patch was useful. In addition, reducing preoperative anxiety by premedication (ie, an oral benzodiazepine) may help avoid fatal arrhythmias provoked by stress for patients with CPVT and dental anxiety.²⁴ DEX, which has an additional analgesic effect, could be effective for invasive oral surgery procedures in patients with CPVT.⁸

Epinephrine is used in local anesthetics to prevent systemic toxicity and promote hemostasis.³⁹ However, epinephrine-containing local anesthetics should be used carefully during dental procedures in patients with cardiac disease. A previous study found a 2- to 3-fold rise in plasma epinephrine values after 1.8 mL intraoral injections of 2% lidocaine with 1:100,000 epinephrine in healthy young patients.⁴⁰ Thus, when weighing the risks and benefits of epinephrine-containing local anesthetics for patients with CPVT, anesthesiologists should always consult with the patient's cardiologist. In this case, we used ropivacaine and mepivacaine plain for local anesthesia.

Moreover, postoperative pain may also lead to ventricular arrhythmias in patients with CPVT. Ropivacaine is a well-tolerated long-acting local anesthetic with a safer cardiotoxicity profile than bupivacaine,⁴¹ and 0.75% ropivacaine has been used to achieve inferior alveolar nerve blocks of long duration to attenuate postoperative pain.⁴² Our patient reported subjective lip and tongue numbness through discharge and well-controlled postoperative pain. Long-acting local anesthetics like ropivacaine can be effective options for controlling postoperative pain in patients with CPVT.

The most critical step in acute arrhythmia management in patients with CPVT could be recognizing the patient's concerns. When ventricular tachycardia occurs, front-line treatment is IV β-blockers.²⁰ Moreover, flecainide¹⁴ and verapamil⁴³ may be effective while amiodarone is ineffective for patients with CPVT.² Epinephrine and other β-agonists can induce fatal arrhythmias. Administering a pure α-adrenergic agonist, like phenylephrine, may be a safe option for patients with CPVT. In the present case, we prepared phenylephrine, atropine, esmolol, and an external defibrillator in preparation for hemodynamic instability or an arrhythmia. However, defibrillation could also induce endogenous catecholamine release and further promote ventricular tachycardia. General anesthesia may further reduce stress, decreasing the risk of ventricular tachycardia, and could be an additional option.²⁰

CONCLUSION

CPVT is characterized by catecholamine-induced fatal arrhythmias, which lead to syncope and sudden death. Because invasive surgical procedures can induce emotional stress in patients with CPVT, there is a need for anesthetic management. DEX-based IV sedation has a centrally acting sympatholytic effect, minimally impacts respiratory stability, and was successfully used in combination with midazolam for oral surgery in a patient with CPVT. Use of DEX should be considered for the anesthetic management of patients with CPVT.