Dexmedetomidine infusion for sedation in a patient with myotonic dystrophy

Summary

Myotonic dystrophy type 1 is the most common muscular dystrophy in adults. Anaesthetic management should take into consideration the numerous body systems affected, including the musculoskeletal; respiratory; cardiovascular; gastro‐intestinal; and central nervous systems. A 42‐year‐old man with myotonic dystrophy presented for septoplasty and bilateral inferior turbinate reductions. He had severe upper and lower extremity myotonia and weakness, pulmonary impairment with non‐obstructive patterns and first‐degree atrioventricular block with reduced ejection fraction. He used bilevel positive airway pressure, a cough assist device and was paced 3% of the time with a single‐chamber pacemaker. To reduce potential complications associated with opioid use and general anaesthetics, an opioid‐free technique was planned using local anaesthetic infiltration and sedation with a dexmedetomidine infusion. The patient maintained spontaneous ventilation and haemodynamic stability, and had an uneventful postoperative course. Dexmedetomidine is a highly selective α2‐adrenergic receptor agonist that has the ability to provide sedation, analgesia and anxiolysis with a stable haemodynamic profile. Avoiding both opioids and general anaesthetics in these patients may decrease the risk of peri‐operative complications.

Introduction

Myotonic dystrophy type 1 is the most common muscular dystrophy in adults, and is inherited in an autosomal dominant manner; its prevalence has been cited to range from one per 100,000 people in Japan to one in 10,000 in Iceland [1]. The worldwide prevalence is estimated to be around one in 20,000 people [1]. It is the result of a cytosine, thymine and guanine trinucleotide repeat in the myotonic dystrophy protein kinase gene [1]. It is a multisystem disorder that affects skeletal and smooth muscle, with effects on the eyes, heart, endocrine system and central nervous system [1]. Clinical manifestations range from mild to severe and can be categorised into three groups with overlapping phenotypes [1]. Mild disease is characterised by cataract and mild myotonia (sustained muscle contraction); life span is normal. Classically, disease is characterised by muscle weakness and wasting; myotonia; cataracts; and often cardiac conduction abnormalities. Adults may become physically disabled and may have a shortened life span. Congenital disease is characterised by hypotonia and severe generalised weakness at birth, often with respiratory insufficiency and early death; intellectual disability is common [1].

Avoiding both opioids and general anaesthesia in patients with myotonic dystrophy may decrease their risk of experiencing peri‐operative complications. Dexmedetomidine is a highly selective α2‐adrenergic receptor agonist that has the ability to provide sedation, analgesia and anxiolysis with a stable haemodynamic profile [2]. These properties make it an attractive choice in patients with myotonic dystrophy.

Report

A 42‐year‐old man with myotonic dystrophy type 1 presented for septoplasty and bilateral inferior turbinate reductions due to a deviated septum. His musculoskeletal symptoms included severe myotonia and weakness in both the upper and lower extremities as well as severe temporalis atrophy and nasal dysarthria. Pulmonary function testing completed 5 months prior showed a 58% reduction in predicted ventilatory capacity with a non‐obstructive pattern. There was no evidence of ventilatory failure and he had normal overnight oximetry. Clinically, he had difficulty with respiration, especially during exertion, but his symptoms were stable. He had sleep‐disordered breathing and reported day time sleepiness, and used bilevel positive airway pressure ventilation intermittently during the day and through the night. He used a cough assist device twice a day.

His cardiac history included a first‐degree atrioventricular block and bi‐fascicular block of the right bundle branch and left anterior fascicle. He had a single‐chamber pacemaker and recent interrogation revealed pacing 3% of the time; his ejection fraction was 44%. He was clinically asymptomatic from a cardiac standpoint with no angina; dyspnoea; syncopal episodes; or oedema. His other comorbidities included cataracts and social smoking.

On examination, he was cachectic with a body mass index (BMI) of 12 kg.m⁻² (height 185.8 cm; weight 42.3 kg). Blood pressure was 120/85 mmHg; heart rate was 74 beats.min⁻¹; respiratory rate was 18 breaths.min⁻¹; and S_pO₂ was 97 % in air. His temperature was 36.4°C.

To reduce potential complications associated with opioid use and general anaesthetics, an opioid‐free anaesthetic was planned using local anaesthetic infiltration and a dexmedetomidine infusion for sedation. On the day of surgery, the patient was brought into the operating room, standard physiologic monitors were applied and a 20‐gauge intravenous cannula was placed in the right arm. Bupivacaine 0.25% with adrenaline 1:200,000 was injected into the septum by the surgeon, bilateral inferior turbinates and nasal mucosa. Oxygen was applied at 8 l.min⁻¹ via a facemask cut to fit over the mouth and the patient was kept spontaneously breathing. Dexmedetomidine 0.54 μg.kg⁻¹ was administered as a loading dose over 6 minutes, followed by an infusion titrated between 0.4 and 0.7μg.kg⁻¹h⁻¹ for the remaining 70 minutes of the case. The patient remained haemodynamically stable throughout and was kept overnight for monitoring with an uneventful postoperative course.

Discussion

The multisystem involvement of myotonic dystrophy type 1 warrants special anaesthetic considerations. Dystrophic organisation of skeletal muscles results in weakness, often involving the facial, laryngeal and respiratory muscles and predisposing patients to respiratory depression and pneumonia [3]. Additionally, patients are prone to myotonia, which can be triggered by suxamethonium; neostigmine; hypothermia; shivering; or surgical stimulation, and may result in hyperkalaemia [3]. Patients with myotonic dystrophy also have low central ventilatory drives, increasing their sensitivity to respiratory depressants, such as opioids [3]. They are prone to arrhythmias and both systolic and diastolic dysfunction due to fibrosis of cardiac myocytes, and inhalational anaesthetics may exacerbate these pre‐existing cardiac comorbidities [3]. Finally, smooth muscle involvement slows peristalsis in the gastro‐intestinal tract, which increases the risk of aspiration and also leads to prolonged postoperative ileus. [3, 4]

Patients with myotonic dystrophy are exquisitely sensitive to drugs that cause respiratory depression, including intravenous and volatile anaesthetic agents; opioids; benzodiazepines; and neuromuscular blocking drugs [3]. Early onset of respiratory muscle weakness in the disease process results in alveolar hypoventilation and poor cough [3]. Patients are also predisposed to abnormal central ventilatory control mechanisms, leading to low central ventilatory drive and central sleep apnoea [5]. These factors lead to an increased incidence of postoperative pulmonary complications [3]. Shivering and hypothermia can induce and prolong myotonic contractures, so normothermia should be maintained throughout the peri‐operative period using active warming devices, fluid warmers and by increasing the room temperature [5]. Suxamethonium should be avoided as it can cause exaggerated contraction, masseter spasm and laryngospasm [3]. Non‐depolarising neuromuscular blocking drugs, if required, should be used judiciously [3]. Anti‐cholinesterases can precipitate myotonia and should also be used cautiously [3]; reports suggest it may be safe to use sugammadex in patients with myotonic dystrophy [3]. A rapid sequence induction should be considered if the patient requires general anaesthesia given the increased risk of aspiration due to delayed gastric emptying and pharyngeal muscle weakness, bearing in mind the risks associated with non‐depolarising neuromuscular blockade [3].

The current literature on anaesthetic management using dexmedetomidine in patients with myotonic dystrophy consists of a case series describing dexmedetomidine sedation for interventional cardiology procedures [6] and for sedation with neuraxial anaesthesia [7]. There have also been reports of the use of dexmedetomidine as an adjuvant to general anaesthesia in order to reduce opioid requirements in the peri‐operative period [8].

Dexmedetomidine offers potential advantages for this particular patient population primarily because ventilation is preserved even at higher doses. [9] That said, the cardiovascular effects of dexmedetomidine should not be overlooked. During higher infusion rates such as a loading dose, hypertension can occur due to activation of the α2β‐adrenergic receptor [9]. Dexmedetomidine usually causes dose‐dependent decreases in blood pressure and heart rate with a synergistic decrease in plasma catecholamines [9]. There are case reports of bradycardia leading to asystole after loading dose administration in conjunction with other anaesthetic agents [9] and second or third‐degree heart block could potentially be exacerbated by administration of dexmedetomidine. This could be particularly deleterious in patients with myotonic dystrophy who may have left ventricular dysfunction and conduction abnormalities [9].

In this case, the patient had a prophylactic pacemaker inserted for an infra‐Hisian conduction block, which was reassuring given the side‐effects of dexmedetomidine. Typically, the loading dose of dexmedetomidine is 0.5–1 μg.kg⁻¹ over 10 minutes depending on age and other comorbidities [9].We chose the lower end of the loading dose because of the extremely low BMI of the patient and low ejection fraction. After 6 minutes of the loading dose, there was decreased consciousness and a decrease in blood pressure not requiring any intervention. We stopped the loading dose at this point and the surgeon infiltrated local anaesthetic, which the patient tolerated well, without exhibiting signs of discomfort once the surgical procedure commenced. We titrated the infusion to maintain deep sedation.

This case report highlights the importance of collaboration with the surgical team. The initial plan made by the attending anaesthetist in anaesthetist with the patient at the pre‐operative clinic was for a general anaesthetic. On the day of surgery, after reviewing the patient’s comorbidities and anatomy, the surgeon and anaesthetist agreed to try sedation as the first option, to which the patient agreed. If the procedure could not be performed under dexmedetomidine sedation or was poorly tolerated, we agreed with the patient and surgeon to convert to a general anaesthetic, keeping in mind that the patient may require a prolonged recovery and possibly postoperative ventilation. Communication was maintained with the surgeon throughout this procedure and was imperative to successful execution of our anaesthetic plan.