Journal of Clinical Anesthesia (2011) 23, 646–648
Case report
Dexmedetomidine controls twitch-convulsive syndrome in the course of uremic encephalopathy Koichi Nomoto MD (Assistant Professor of Anesthesiology)a,⁎, Corey Scurlock MD, MBA (Associate Professor of Anesthesiology and Cardiothoracic Surgery)a,b, David Bronster MD (Associate Professor of Neurology)c a
Department of Anesthesiology, Mount Sinai School of Medicine, New York, NY 10029, USA Department of Surgery, Mount Sinai School of Medicine, New York, NY 10029, USA c Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA b
Received 4 May 2010; revised 19 January 2011; accepted 25 January 2011
Keywords: Chronic renal insufficiency; Dexmedetomidine; Twitch-convulsive syndrome; Uremic encephalopathy
Abstract An 85 year old man with a history of chronic renal insufficiency was admitted to the cardiothoracic intensive care unit after aortic valve replacement. His postoperative course was marked by acute oliguric renal failure for high blood urea nitrogen (BUN) and acute hyperactive delirium. At this time he also developed tremors with muscle twitching; he received no other form of sedatives. A neurology consult made the diagnosis of twitch-convulsive syndrome associated with uremic encephalopathy. While the patient was receiving the dexmedetomidine infusion, the signs of the twitch-convulsive syndrome, particularly the twitching and tremors, disappeared. Within 30 minutes of the end of the dexmedetomidine infusion, symptoms of the twitch-convulsive syndrome returned, manifesting as acute tremulousness. After several dialysis treatments, his BUN decreased and the dexmedetomidine was weaned, without return of the symptoms of twitch-convulsive syndrome. Published by Elsevier Inc.
1. Introduction Dexmedetomidine is an alpha-2 agonist that provides sedation, synergism with analgesics, and a potential antinociceptive effect without suppressing respiratory function [1-6]. It has received approval for use as sedation of nonintubated patients before and/or during surgical and other procedures [7]. With its unique combination of pharmacological properties, dexmedetomidine offers signif-
⁎ Correspondence and reprint request: Koichi Nomoto, MD, Department of Anesthesiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1010, New York, NY 10029, USA. Fax: +1 212 426 2009. E-mail address:
[email protected] (K. Nomoto). 0952-8180/$ – see front matter. Published by Elsevier Inc. doi:10.1016/j.jclinane.2011.01.011
icantly lower rates of postoperative delirium [8] and is less prone to causing delirium than other agents [9,10]. Thus, dexmedetomidine is an ideal sedative drug for use in the intensive care unit (ICU) as it bypasses the gamma-amino butyric acid (GABA) receptor and has a delirium-sparing effect [8,10,11]. Diseases of the kidney, especially acute renal failure, may lead to uremia, with accumulation of toxic substances causing encephalopathy. A variety of involuntary motor phenomena form a condition known as the twitchconvulsive syndrome [12,13]. The uremic twitch-convulsive syndrome is an often overlooked or misinterpreted clinical presentation in ICU patients with renal failure. First described by Adams and Victor in 1977, it presents with varying degrees of muscle twitching and fasciculations, arrhythmic tremors, random
Dexmedetomidine and twitch-convulsive syndrome and asynchronous jerking of the limbs, frank myoclonus, asterixis, and seizures [13]. When the seizures are severe, they may resemble convulsions and require an electroencephalogram (EEG) to differentiate. Alternatively, particularly if it is left untreated, it may progress to true seizure activity. The patient's sensorium may be clear or altered, and frank delirium may be present. Alterations of renal function are noted. When twitching and tremors are mild, they may require no specific pharmacologic intervention, and disappear with resolution of the renal insufficiency (including dialysis). However, the jerking and myoclonus may be severe, unpleasant for patient, family and staff, and interfere with patient care. Although benzodiazepines are useful to suppress symptoms and treat the seizure, there are drawbacks. Benzodiazepines may worsen existing delirium, and may have unpredictable metabolic clearance in ICU patients with end-organ dysfunction. Dexmedetomidine allowed treatment of agitation and uremic twitch-convulsive syndrome without the confounding side effect of respiratory compromise.
2. Case report An 85 year old man with a history of severe aortic stenosis, coronary artery disease, and chronic renal insufficiency, underwent aortic valve replacement and coronary artery bypass graft. He was admitted to the cardiothoracic ICU with minimum inotropic support. Given his age, his weaning was performed gradually and his trachea was extubated on postoperative day (POD) 3. The remainder of his postoperative course was notable for development of acute or chronic oliguric renal failure. On POD 8, he developed acute hyperactive delirium in addition to his renal failure. All other inciting causes of delirium such as hypoxia, metabolic disorders, iatrogenic medications, and infection were ruled out and a neurology consult was obtained. During this period, he also developed tremors, muscle twitching, and asterixis, which was diagnosed as twitch-convulsive syndrome in the setting of acute renal failure with uremia. A dexmedetomidine infusion (0.6 μg/kg/hr) without a loading dose was given for his agitation. Seventy minutes after initiation of the dexmedetomidine infusion, the agitation and symptoms of uremic twitch- convulsive syndrome resolved. On POD 9, the patient remained alert but confused, and he was weaned off the dexmedetomidine for improvement of his agitation. Within 30 minutes of weaning, he again presented with recurrent symptoms of muscle twitching and asynchronous tremors. The dexmedetomidine infusion (0.4 μg/kg/hr) was readministered for recurrence of the symptoms. About 60 minutes after initiation of the dexmedetomidine, the symptoms again resolved. This event occurred once more several hours later when the dexmedetomidine was stopped to evaluate his neurologic status; it was resumed to control his twitching and myoclonus with jerking. He underwent hemodialysis for his uremic encephalopathy on PODs 9 and
647 10, with reduction of his blood urea nitrogen (BUN) and the symptoms of twitch-convulsive syndrome. At this point, his dexmedetomidine infusion was discontinued. The patient was discharged from the ICU on POD 13. He was readmitted to the ICU much later in his hospital course with signs and symptoms of sepsis and mediastinits. Over the next several months, he developed multi-system organ failure and he eventually died.
3. Discussion The alpha-2 agonists, clonidine and dexmedetomidine, represent a major alternative to the GABA agonists for ICU sedation. Dexmedetomidine was first approved by the Food and Drug Administration in 1999, and it is the only intravenous alpha-2 agonist available in the United States. Both medications bind to noradrenergic receptors in the brain, spinal cord, and throughout the body. Distinct from GABA agonists, alpha-2 agonists provide sedation that is synergistic with analgesics, and cause little or no respiratory depression [1,5,7]. Dexmedetomidine is well suited for use in the ICU environment, allowing sedated patients to be quickly aroused and oriented on demand. A stereotypical movement disorder associated with uremic encephalopathy is the twitch-convulsive syndrome, consisting of varying degrees of muscle twitching, fasciculations, tremors, random myoclonus, asterixis, and seizures [12,13]. Twitch-convulsive syndrome is an often overlooked or misinterpreted clinical presentation in patients with acute renal failure. Symptoms may range from mild to severe, and may progress to seizures if left untreated. Typically milder forms of the syndrome do not require any treatment, and symptoms resolve on reduction of BUN. The exact cause of the twitch-convulsive syndrome is unknown; however, in the presence of uremia, organic substances accumulate. These substances include 4 important guanidino compounds: creatinine, guanidine, guanidosuccinic acid (GSA), and methylguanidine (MG). These compounds all induce myocolonus, and the latter two are especially epileptogenic. The 4 compounds may be the basis of seizures and the uremic twitch-convulsive syndrome [14,15]. Guanidino compounds seem to exert their effects via the GABA system [16]. Dexmedetomidine does not bind to the GABA receptor and thus may minimize the development of delirium by decreasing the release of norepinephrine. Therefore, dexmedetomidine is an emerging treatment option for delirium in patients who require reliable, serial neurological testing [8,9,17]. In this case, the patient developed delirium and acute oliguric renal failure with a high BUN that was accompanied by twitch-convulsive syndrome. Dexmedetomidine was administered to treat his symptoms of delirium, with the unexpected benefit of controlling his twitch-convulsive syndrome. The dexmedetomidine was discontinued twice in 24 hours for neurologic assessment. During this time, his
648 twitch-convulsive syndrome symptoms returned. Interestingly, 60 to 70 minutes after each restart of the dexmedetomidine infusion, the symptoms of the twitch-convulsive syndrome were suppressed. The mechanism of this suppression effect is unknown. However, in animal studies, GABA-based agents were unable to suppress clonic seizure activity induced by GSA, the most potent guanidino compound. Rather, seizures induced by GSA were blocked by administration of NMethyl-D-Aspartate (NMDA) receptor antagonists; thus, NMDA receptors are involved with MSA convulsions [16]. In addition, NMDA antagonists increase GABA levels in cerebrospinal fluid [13]. Similarly, dexmedetomidine depresses NMDA receptors in animal models [18]. Treatment of delirium in acute renal failure with dexmedetomidine may have the unintended but beneficial effect of suppressing the symptoms of twitch-convulsive syndrome.
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