Dexmedetomidine Suppressed Involuntary Movement in a Patient with Cerebral Palsy Dustin Dayton, MD, and Anna K. Kowalczyk, MD Involuntary movements in patients with cerebral palsy can interfere with invasive procedures performed under sedation. We present a case of a 58-year-old man with cerebral palsy, who successfully underwent a cardiac catheterization while sedated with IV dexmedetomidine. The patient’s involuntary movements were suppressed, which allowed the cardiologist to perform the procedure on an immobile, cooperative patient, all while maintaining patient comfort, stable hemodynamics, as well as adequate oxygenation and ventilation. This novel use of dexmedetomidine might facilitate monitored anesthesia care in patients otherwise requiring general anesthesia. (A&A Case Reports. 2014;3:40–1.)
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lpha-2 agonists have many uses in the perioperative period including anxiolysis, sedation, and analgesia. By binding to presynaptic α2 adrenergic receptors, they inhibit central sympathetic outflow and reduce peripheral norepinephrine release.1,2 There are 3 subtypes of the α2 receptor: α2A, α2B, and α2C. Different subtypes may be uniquely responsible for some of the specific actions of α2 agonists.3 We describe a case wherein dexmedetomidine, used as a sedative for an invasive procedure, suppressed involuntary movements in a patient with cerebral palsy. The patient provided verbal and written consent to publish this case.
CASE DESCRIPTION
A 58-year-old, left hand-dominant man, with a history of spastic tetraplegic cerebral palsy, presented for inferior vena cava filter placement as well as right and left heart catheterization. His comorbidities included restrictive lung disease treated with continuous oxygen (2 L/min) due to severe kyphoscoliosis and right ventricular (RV) dysfunction due to restrictive lung disease and also chronic thromboembolic disease. A transthoracic echocardiogram 2 months before admission revealed an RV systolic pressure of 85 mm Hg with a severely dilated RV and reduced RV systolic function. The patient also had a history of severe lower back pain. Both his spasticity and low back pain were treated with an intrathecal infusion of baclofen 65.08 mcg/d, morphine 0.6882 mg/d, and clonidine 0.6882 mg/d. Additionally, he was taking oral orphenadrine, oxycodone/acetaminophen, diazepam, and amitriptyline. Most concerning for this procedure, however, were the patient’s pronounced involuntary, twitch-like movements of his extremities, upper greater than lower, that interfered with performing the procedure with monitored anesthesia care. From the Department of Anesthesiology and Pain Medicine, University of California, Davis Medical Center, Sacramento, California. Accepted for publication February 19, 2014. Funding: None. The authors declare no conflicts of interest. Address correspondence to Anna K. Kowalczyk, MD, Department of Anesthesiology and Pain Medicine, University of California, Davis Medical Center, 4150 V St., Suite 1200, Sacramento, CA 95817. Address e-mail to anna. [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000050
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Due to the patient’s involuntary movements, the cardiologist requested a general anesthetic. However, after careful consideration of risks and benefits, we concluded that the risks of myocardial depression from volatile and IV anesthetics, as well as potential difficulty with gas exchange during positive pressure ventilation in this patient, seemed to outweigh the benefit of a general anesthetic. We decided to proceed with monitored anesthesia care, aiming to prevent patient movement while maintaining adequate ventilation and oxygenation, as well as patient comfort. We chose dexmedetomidine as the main sedative drug primarily to avoid respiratory depression, which would result from administration of other sedatives such as opioids or propofol, and avoid the resultant hypoxia and hypercarbia that could precipitate acute RV failure. In the procedure room and after applying standard American Society of Anesthesiologists monitors, his baseline arterial blood pressure was 131/86 mm Hg and heart rate was 72 bpm. Supplemental oxygen was delivered via nasal cannula. The patient continued to have myoclonic movements during this time, and a dexmedetomidine infusion was initiated at 0.007 mcg/kg/min. No initial loading dose was administered. No changes to the intrathecal pump rate were made. Approximately 20 minutes after initiating the dexmedetomidine infusion, the patient’s twitchlike movements gradually diminished and subsided by 30 minutes. The dexmedetomidine infusion was titrated to Ramsay Sedation Scale score of 2 and ranged from 0.007 to 0.01 mcg/kg/min. In addition, 25 mcg of remifentanil was administered as a 1-time bolus. No other sedatives were given. Intraoperatively, the patient’s arterial blood pressure ranged from 115/62 to 136/90 mm Hg and his heart rate from 58 to 77 bpm. His oxyhemoglobin saturation ranged from 93% to 99% on 6 L/min of oxygen via nasal cannula, and he had no episodes of apnea or hypopnea. The procedure lasted approximately 1.5 hours. At the conclusion of the procedure, the dexmedetomidine infusion rate was 0.01 mcg/kg/min and it was terminated on removal of surgical drapes. The patient was transferred to recovery. During his recovery stay, the involuntary movements returned approximately 30 minutes after discontinuation of the drug.
DISCUSSION
Several case reports and animal studies have described the effect of dexmedetomidine on movement disorders. August 1, 2014 • Volume 3 • Number 3
Nomoto et al.4 described a patient with uremic encephalopathy and twitch convulsive syndrome, in whom twitching and tremors disappeared after initiation of the dexmedetomidine infusion and reappeared within 30 minutes of its discontinuation. Girgin et al.5 demonstrated the effect of dexmedetomidine on patients with tetanus. While dexmedetomidine did not fully control muscle spasms, it did decrease their frequency and severity and reduced the use of sedative, analgesic, and muscle-relaxing drugs, which in turn improved cardiovascular stability. In mice, use of dexmedetomidine demonstrated a dose-dependent reduction in locomotor activity likely related to its effect on α2A receptor subtype.6–9 The etiology of our patient’s myoclonic movements was not clear. Whether they were associated with the cerebral palsy itself or a result of pharmacotherapy remains unknown. The continuous intrathecal administration of morphine has been shown to result in reduction of inhibitory central output leading to involuntary movement.10 The myoclonic activity in this patient persisted despite intrathecal infusion of clonidine, another α2 agonist. Not until the IV dexmedetomidine infusion was initiated did the patient’s involuntary movements subside. Dexmedetomidine is a very specific α2 agonist, with an α2A to α1 selectivity of 1300 to 1. In comparison, clonidine has an α2A to α1 selectivity of only 30 to 1.3 This increased selectivity for the α2 receptor could possibly explain the greater efficacy for suppressing myoclonic movements in our patient. Also, the more intense α2 effect achieved from IV administration may have played a role. Furthermore, it is possible that the observed effect was not due to dexmedetomidine alone, but because the drug exhibited a synergistic or additive effect with clonidine. Since the patient was also receiving morphine, baclofen, diazepam, and amitriptyline, the therapeutic effect could have been due to the interaction of dexmedetomidine with 1 or more of these drugs. As the life expectancy of patients with cerebral palsy increases, they present for invasive procedures with increased frequency. They are often burdened with numerous comorbidities that place them at an increased risk for
August 1, 2014 • Volume 3 • Number 3
complications from general anesthesia. The ability to avoid general anesthesia and provide adequate sedation that ensures an immobile patient, yet provides stable hemodynamics with adequate gas exchange, is extremely beneficial. Whether the use of dexmedetomidine can be extended to other types of involuntary movement disorders is beyond the scope of this case report. E REFERENCES 1. Jalonen J, Hynynen M, Kuitunen A, Heikkilä H, Perttilä J, Salmenperä M, Valtonen M, Aantaa R, Kallio A. Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology 1997;86:331–45 2. Wijesundera DN, Naik JS, Beatie S. Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: a metaanalysis. Am J Med 2003;114:742–52 3. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 1999;54:146–65 4. Nomoto K, Scurlock C, Bronster D. Dexmedetomidine controls twitch-convulsive syndrome in the course of uremic encephalopathy. J Clin Anesth 2011;23:646–8 5. Girgin NK, Iscimen R, Gurbet A, Kahveci F, Kutlay O. Dexmedetomidine sedation for the treatment of tetanus in the intensive care unit. Br J Anaesth 2007;99:599–600 6. Votava M, Hess L, Slíva J, Krsiak M, Agová V. Dexmedetomidine selectively suppresses dominant behaviour in aggressive and sociable mice. Eur J Pharmacol 2005;523:79–85 7. Lakhlani PP, MacMillan LB, Guo TZ, McCool BA, Lovinger DM, Maze M, Limbird LE. Substitution of a mutant alpha2aadrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Proc Natl Acad Sci U S A 1997;94:9950–5 8. Hunter JC, Fontana DJ, Hedley LR, Jasper JR, Lewis R, Link RE, Secchi R, Sutton J, Eglen RM. Assessment of the role of alpha2adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice. Br J Pharmacol 1997;122:1339–44 9. Lähdesmäki J, Sallinen J, MacDonald E, Sirviö J, Scheinin M. Alpha2-adrenergic drug effects on brain monoamines, locomotion, and body temperature are largely abolished in mice lacking the alpha2A-adrenoceptor subtype. Neuropharmacology 2003;44:882–92 10. Kakinohana M, Marsala M, Carter C, Davison JK, Yaksh TL. Neuraxial morphine may trigger transient motor dysfunction after a noninjurious interval of spinal cord ischemia: a clinical and experimental study. Anesthesiology 2003;98:862–70
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A
lpha-2 agonists have many uses in the perioperative period including anxiolysis, sedation, and analgesia. By binding to presynaptic α2 adrenergic receptors, they inhibit central sympathetic outflow and reduce peripheral norepinephrine release.1,2 There are 3 subtypes of the α2 receptor: α2A, α2B, and α2C. Different subtypes may be uniquely responsible for some of the specific actions of α2 agonists.3 We describe a case wherein dexmedetomidine, used as a sedative for an invasive procedure, suppressed involuntary movements in a patient with cerebral palsy. The patient provided verbal and written consent to publish this case.
CASE DESCRIPTION
A 58-year-old, left hand-dominant man, with a history of spastic tetraplegic cerebral palsy, presented for inferior vena cava filter placement as well as right and left heart catheterization. His comorbidities included restrictive lung disease treated with continuous oxygen (2 L/min) due to severe kyphoscoliosis and right ventricular (RV) dysfunction due to restrictive lung disease and also chronic thromboembolic disease. A transthoracic echocardiogram 2 months before admission revealed an RV systolic pressure of 85 mm Hg with a severely dilated RV and reduced RV systolic function. The patient also had a history of severe lower back pain. Both his spasticity and low back pain were treated with an intrathecal infusion of baclofen 65.08 mcg/d, morphine 0.6882 mg/d, and clonidine 0.6882 mg/d. Additionally, he was taking oral orphenadrine, oxycodone/acetaminophen, diazepam, and amitriptyline. Most concerning for this procedure, however, were the patient’s pronounced involuntary, twitch-like movements of his extremities, upper greater than lower, that interfered with performing the procedure with monitored anesthesia care. From the Department of Anesthesiology and Pain Medicine, University of California, Davis Medical Center, Sacramento, California. Accepted for publication February 19, 2014. Funding: None. The authors declare no conflicts of interest. Address correspondence to Anna K. Kowalczyk, MD, Department of Anesthesiology and Pain Medicine, University of California, Davis Medical Center, 4150 V St., Suite 1200, Sacramento, CA 95817. Address e-mail to anna. [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000050
40 cases-anesthesia-analgesia.org
Due to the patient’s involuntary movements, the cardiologist requested a general anesthetic. However, after careful consideration of risks and benefits, we concluded that the risks of myocardial depression from volatile and IV anesthetics, as well as potential difficulty with gas exchange during positive pressure ventilation in this patient, seemed to outweigh the benefit of a general anesthetic. We decided to proceed with monitored anesthesia care, aiming to prevent patient movement while maintaining adequate ventilation and oxygenation, as well as patient comfort. We chose dexmedetomidine as the main sedative drug primarily to avoid respiratory depression, which would result from administration of other sedatives such as opioids or propofol, and avoid the resultant hypoxia and hypercarbia that could precipitate acute RV failure. In the procedure room and after applying standard American Society of Anesthesiologists monitors, his baseline arterial blood pressure was 131/86 mm Hg and heart rate was 72 bpm. Supplemental oxygen was delivered via nasal cannula. The patient continued to have myoclonic movements during this time, and a dexmedetomidine infusion was initiated at 0.007 mcg/kg/min. No initial loading dose was administered. No changes to the intrathecal pump rate were made. Approximately 20 minutes after initiating the dexmedetomidine infusion, the patient’s twitchlike movements gradually diminished and subsided by 30 minutes. The dexmedetomidine infusion was titrated to Ramsay Sedation Scale score of 2 and ranged from 0.007 to 0.01 mcg/kg/min. In addition, 25 mcg of remifentanil was administered as a 1-time bolus. No other sedatives were given. Intraoperatively, the patient’s arterial blood pressure ranged from 115/62 to 136/90 mm Hg and his heart rate from 58 to 77 bpm. His oxyhemoglobin saturation ranged from 93% to 99% on 6 L/min of oxygen via nasal cannula, and he had no episodes of apnea or hypopnea. The procedure lasted approximately 1.5 hours. At the conclusion of the procedure, the dexmedetomidine infusion rate was 0.01 mcg/kg/min and it was terminated on removal of surgical drapes. The patient was transferred to recovery. During his recovery stay, the involuntary movements returned approximately 30 minutes after discontinuation of the drug.
DISCUSSION
Several case reports and animal studies have described the effect of dexmedetomidine on movement disorders. August 1, 2014 • Volume 3 • Number 3
Nomoto et al.4 described a patient with uremic encephalopathy and twitch convulsive syndrome, in whom twitching and tremors disappeared after initiation of the dexmedetomidine infusion and reappeared within 30 minutes of its discontinuation. Girgin et al.5 demonstrated the effect of dexmedetomidine on patients with tetanus. While dexmedetomidine did not fully control muscle spasms, it did decrease their frequency and severity and reduced the use of sedative, analgesic, and muscle-relaxing drugs, which in turn improved cardiovascular stability. In mice, use of dexmedetomidine demonstrated a dose-dependent reduction in locomotor activity likely related to its effect on α2A receptor subtype.6–9 The etiology of our patient’s myoclonic movements was not clear. Whether they were associated with the cerebral palsy itself or a result of pharmacotherapy remains unknown. The continuous intrathecal administration of morphine has been shown to result in reduction of inhibitory central output leading to involuntary movement.10 The myoclonic activity in this patient persisted despite intrathecal infusion of clonidine, another α2 agonist. Not until the IV dexmedetomidine infusion was initiated did the patient’s involuntary movements subside. Dexmedetomidine is a very specific α2 agonist, with an α2A to α1 selectivity of 1300 to 1. In comparison, clonidine has an α2A to α1 selectivity of only 30 to 1.3 This increased selectivity for the α2 receptor could possibly explain the greater efficacy for suppressing myoclonic movements in our patient. Also, the more intense α2 effect achieved from IV administration may have played a role. Furthermore, it is possible that the observed effect was not due to dexmedetomidine alone, but because the drug exhibited a synergistic or additive effect with clonidine. Since the patient was also receiving morphine, baclofen, diazepam, and amitriptyline, the therapeutic effect could have been due to the interaction of dexmedetomidine with 1 or more of these drugs. As the life expectancy of patients with cerebral palsy increases, they present for invasive procedures with increased frequency. They are often burdened with numerous comorbidities that place them at an increased risk for
August 1, 2014 • Volume 3 • Number 3
complications from general anesthesia. The ability to avoid general anesthesia and provide adequate sedation that ensures an immobile patient, yet provides stable hemodynamics with adequate gas exchange, is extremely beneficial. Whether the use of dexmedetomidine can be extended to other types of involuntary movement disorders is beyond the scope of this case report. E REFERENCES 1. Jalonen J, Hynynen M, Kuitunen A, Heikkilä H, Perttilä J, Salmenperä M, Valtonen M, Aantaa R, Kallio A. Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology 1997;86:331–45 2. Wijesundera DN, Naik JS, Beatie S. Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: a metaanalysis. Am J Med 2003;114:742–52 3. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 1999;54:146–65 4. Nomoto K, Scurlock C, Bronster D. Dexmedetomidine controls twitch-convulsive syndrome in the course of uremic encephalopathy. J Clin Anesth 2011;23:646–8 5. Girgin NK, Iscimen R, Gurbet A, Kahveci F, Kutlay O. Dexmedetomidine sedation for the treatment of tetanus in the intensive care unit. Br J Anaesth 2007;99:599–600 6. Votava M, Hess L, Slíva J, Krsiak M, Agová V. Dexmedetomidine selectively suppresses dominant behaviour in aggressive and sociable mice. Eur J Pharmacol 2005;523:79–85 7. Lakhlani PP, MacMillan LB, Guo TZ, McCool BA, Lovinger DM, Maze M, Limbird LE. Substitution of a mutant alpha2aadrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Proc Natl Acad Sci U S A 1997;94:9950–5 8. Hunter JC, Fontana DJ, Hedley LR, Jasper JR, Lewis R, Link RE, Secchi R, Sutton J, Eglen RM. Assessment of the role of alpha2adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice. Br J Pharmacol 1997;122:1339–44 9. Lähdesmäki J, Sallinen J, MacDonald E, Sirviö J, Scheinin M. Alpha2-adrenergic drug effects on brain monoamines, locomotion, and body temperature are largely abolished in mice lacking the alpha2A-adrenoceptor subtype. Neuropharmacology 2003;44:882–92 10. Kakinohana M, Marsala M, Carter C, Davison JK, Yaksh TL. Neuraxial morphine may trigger transient motor dysfunction after a noninjurious interval of spinal cord ischemia: a clinical and experimental study. Anesthesiology 2003;98:862–70
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