Anesthetic Management of Coronary Artery Bypass Grafting in a Patient with Charcot-Marie-Tooth Disease and Multivessel Coronary Artery Disease

Background

Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuromuscular disorder, with an estimated prevalence of 1 in 2500 individuals [1]. Common clinical presentations consist of distal-predominant atrophy of lower extremity muscles with accompanying sensation loss, various foot deformities, including high arches and hammer toes with intrinsic muscle wasting, atrophy of intrinsic hand and forearm muscles with sensation loss, and autonomic dysfunction [2]. The primary pathophysiology of CMT, involving myelin protein dysfunction and axonal degeneration, is of concern in patients undergoing general anesthesia. Literature suggests a potential increased sensitivity to non-depolarizing neuromuscular blocking agents and raises concerns for malignant hyperthermia in patients with CMT [3]. In cardiac surgery, additional considerations must be given to patients with CMT. Cardiomyopathy resulting from underlying muscular and autonomic dysfunction can be prone to further insult during coronary artery bypass graft surgery (CABG), specifically in the form of decreased left ventricle performance and potential ischemia. Additionally, the presence of atrial and ventricular arrhythmias has been documented in CMT patients undergoing anesthesia [4]. Thus, appropriate preoperative evaluation and perioperative management is essential in CMT patients undergoing general anesthesia for CABG and other cardiac procedures. We present a case of a 61-year-old woman with a past medical history of CMT and multivessel coronary artery disease status post multiple percutaneous coronary interventions with new-onset chest pain undergoing CABG.

Case Report

A 61-year-old woman with a past medical history of CMT (diagnosed previously via electromyography results and duplication of peripheral myelin protein 22 on genetic testing), coronary artery disease (status post multiple percutaneous coronary interventions), obstructive sleep apnea, non-insulin dependent diabetes mellitus, hypertension, hypercholesteremia, and gastroesophageal reflux disease presented to the Cardiology Clinic with dizziness, substernal chest pain akin to her typical angina, and hypotension (90/59 mmHg). She was transferred to the Emergency Department and evaluated by the inpatient cardiology team. Electrocardiography revealed normal sinus rhythm with a nonspecific T-wave abnormality, while the troponin trend showed no acute ischemic changes. She was started on a heparin drip and resumed home aspirin, clopidogrel, ranolazine, and atorvastatin, while metoprolol, losartan, and isosorbide mononitrate were held due to hypotension. She was taken for cardiac catheterization, which revealed the following: 70% occlusion of the proximal left anterior descending (LAD) artery, 80% in-stent restenosis of the mid-LAD artery, 90% occlusion of the first diagonal branch of the LAD artery, 70% in-stent restenosis of the second marginal branch of the LAD artery, and 70% in-stent restenosis of the proximal right coronary artery. Following catheterization, the cardiothoracic surgery team was consulted, and the patient was deemed appropriate for CABG. Transthoracic echo-cardiography revealed a left ventricular ejection fraction of 55%, normal left ventricular wall thickness, normal right ventricular function, and no significant valvular abnormalities. On admission day 3, CABG was performed.

In the preoperative holding area, the anesthesiologist performed a thorough history and physical examination. The patient stated that she had undergone prior bladder surgery, hysterectomy, tubal ligation, and tonsillectomy without issue; however, no anesthetic records were available. Per the patient-provided history, she had no family history of malignant hyperthermia. Given the equivocal findings regarding CMT and malignant hyperthermia in the literature [5–7], a conservative approach to anesthesia using total intravenous anesthesia and a malignant hyperthermia protocol was used. Preoperatively, vaporizers were removed from the anesthesia machine and cardio-pulmonary bypass circuit; the anesthesia machine was flushed with high fresh gas flow for 2 minutes; the anesthesia circuit, bag, and carbon dioxide absorbent were changed; dantrolene was readily available; and activated charcoal filters for malignant hyperthermia-susceptible patients were placed at the inspiratory and expiratory limbs of the anesthesia machine.

Following placement of standard monitors, invasive blood pressure monitoring was obtained via the left radial artery prior to inducing the patient with intravenous propofol, lidocaine, fentanyl, and 1 mg/kg (70 mg) rocuronium. Endotracheal intubation was subsequently performed uneventfully. Total intravenous anesthesia was maintained with propofol and remifentanil infusions (80–100 mcg/kg/min and 0.05–0.1 mcg/kg/min, respectively). A right internal jugular 9-French central venous catheter was placed, consistent with institutional practice for cardiac surgery. Hemodynamic support with phenylephrine, norepinephrine, and epinephrine was periodically required throughout the case. A peripheral nerve stimulator was used to guide neuromuscular blockade. Rocuronium (25 mg) was re-dosed once during the pre-bypass period. Ketamine was avoided to allow for more accurate bispectral index monitoring in the setting of total intravenous anesthesia. Preoperative transesophageal echocardiography (TEE) showed a left ventricular ejection fraction of 50% to 55%, grade II diastolic dys-function, normal right ventricular function and no significant valvular abnormalities. On cardiopulmonary bypass, the following bypass grafts were performed: left internal mammary artery to distal LAD artery, saphenous vein graft to distal obtuse marginal artery, and saphenous vein graft to distal posterior descending artery. Post-cardiopulmonary bypass TEE showed an ejection fraction of 55% in the setting of epinephrine infusion (0.03 mcg/kg/min), with no new regional wall motion abnormalities. Grossly normal right ventricular function was observed, consistent with the patient’s pre-bypass baseline. Sugammadex (300 mg, 4 mg/kg) was used for reversal of rocuronium after skin closure.

The patient was transferred to the Cardiovascular Intensive Care Unit in stable condition and remained on an epinephrine infusion. She was extubated on postoperative day 0, weaned from all vasopressor support and restarted on clopidogrel and atorvastatin on postoperative day 1, and restarted on metoprolol on postoperative day 2. She was transferred to the step-down unit on postoperative day 4, and had her chest tubes removed on postoperative day 5. On postoperative day 6, her epicardial pacing wires were removed, and she was discharged to home with plans for home health assistance.

Discussion

CMT is a hereditary peripheral neuropathy involving both sensory and motor domains in a distal-predominant fashion [8]. Inheritance is often autosomal dominant, though other sub-types have been described in literature, with 4 genes comprising over 90% of CMT cases [1]. Owing to the heterogeneity of CMT presentation, the anesthetic management and surgical plans for CMT patients require special attention. Concerning patient factors that have been previously documented and must be considered in a patient with CMT undergoing surgical intervention are unpredictable responses to non-depolarizing neuromuscular blocking agents, potential risk of malignant hyperthermia, and cardiac complications, such as arrhythmia and exacerbation of underlying myocardial and autonomic dysfunction [3,4]. Figure 1 summarizes important anesthetic considerations for patients with CMT.

Non-depolarizing neuromuscular blocking agents, including the aminosteroidal and benzylisoquinolinium structural classes, are often preferred for use over succinylcholine in patients with CMT, owing to the risk of hyperkalemia with depolarization associated with the chronic denervation state, although this viewpoint is not consistently held [9]. Despite a general preference for the use of non-depolarizing neuromuscular blocking agents, however, these agents also have a degree of theoretical unpredictability, attributable to the loss of motor units seen in the disease process, potentially resulting in prolongation of muscle relaxation [5]. While some previous case reports have supported this prolonged duration [10], others have observed no change in the degree of neuromuscular blockade compared with that in non-CMT patients [11]. To complicate matters in the age of sugammadex, there has also been a case report describing prolonged neuromuscular blockade with rocuronium refractory to sugammadex reversal [12]. In our patient with CMT undergoing CABG, there was no prolongation in blockade observed with use of rocuronium, and sugammadex was successfully used for reversal.

The degree of association between malignant hyperthermia and CMT remains unknown. The purported relationship between malignant hyperthermia and CMT seems to be derived from a case report from 1985 by Roelofse et al that states, “Although malignant hyperthermia is not thought to be a problem, inhalational anaesthestic agents must be administered with great caution.” [7]. Other reports mention a possible association between CMT and malignant hyperthermia [3,6]. However, a study by Antognini in 1992 of over 100 surgical operations reported no cases of malignant hyperthermia when agents such as succinylcholine and volatile gases were used [5]. Nevertheless, in the present case, a malignant hyperthermia protocol was followed in an effort to treat the patient conservatively, given the conflicting information found in the literature in real-time preoperatively. Succinylcholine was avoided, inhalational agent vaporizers were removed to prevent inadvertent use, the carbon-dioxide absorbent was removed and replaced, the anesthesia machine was flushed with high gas flows, and dantrolene was readily available. Total intravenous anesthesia with propofol and remifentanil infusions allowed for the avoidance of volatile anesthetics intraoperatively and while on cardiopulmonary bypass. As a result of our protocol, there was little concern for malignant hyperthermia in the described case. Additionally, ketamine was not used due to the potential for a paradoxical increase in the bispectral index [13–16], which may have blurred determination of anesthetic depth intraoperatively, especially on cardiopulmonary bypass when volatile agent is traditionally used in the cardiopulmonary bypass circuit.

Proper perioperative evaluation of potential underlying cardiovascular manifestations is necessary. Previous reports of patients with CMT have described cases of individuals presenting with sinus node dysfunction, long QT syndrome, atrial flutter, atrioventricular block, and cardiomyopathy [17–19]. Left ventricular hypertrophy, which can occur secondary to autonomic dysfunction-induced cardiomyopathy in patients with CMT, should be given special scrutiny on evaluation with echo-cardiography [20]. Patients with CMT also have reduced diaphragmatic strength secondary to involvement of the phrenic nerve [21]. Therefore, in cases of intraoperative cardiopulmonary failure, consideration must be given to sequalae of CMT pathophysiology, including diaphragmatic weakness or the presence of an underlying cardiac abnormality. Our patient had no concerning findings on echocardiography, electrocardiogram, or chest radiography. However, given these possibilities, a decision was made not to extubate in the operating room after routine cardiac surgery, despite intraoperative extubation after cardiac surgery being common at our institution [22].

Conclusions

The development of an anesthetic management plan in a patient with CMT requires that the anesthesiologist be fully aware of the possible disease manifestations that can result secondary to the pathophysiology. In the case presented here, the patient successfully underwent CABG using total intravenous anesthesia with propofol and remifentanil infusions with rocuronium for paralysis, without complication. While many of the potential anesthetic complications associated with the CMT disease process may be rare or not well elucidated in the literature, we believe using a conservative, tailored approach for the anesthetic management of these individuals is paramount to ensure patient safety and optimize perioperative outcomes.