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Multiple anesthetics for a patient with stiff-person syndrome
Journal of Clinical Anesthesia (2016) 31, 197–199
Case Report
Multiple anesthetics for a patient with stiff-person syndrome☆ Jessica M. Cassavaugh MD, PhD, Todd M. Oravitz MD ⁎ University of Pittsburgh, VA Pittsburgh Healthcare System Anesthesia Service, Room 3N221B, University Dr C, Pittsburgh, PA, 15240, USA Received 9 March 2015; accepted 4 February 2016
Keywords: GABA signaling; Neuromuscular blockade; Stiff-person syndrome
Abstract Stiff-person syndrome is a progressive disease of muscle rigidity and spasticity due to a deficiency in the production of γ-aminobutyric acid. Because of the rarity of the condition, little is known about effects of anesthesia on patients with stiff-person syndrome. This report describes the clinical course for a single patient with stiff-person syndrome who received general anesthesia on 3 separate occasions. Her anesthetics included use of both neuromuscular blockade and volatile agents. Unlike several previous reports regarding anesthesia and stiff-person syndrome, the postoperative period for this patient did not require prolonged intubation or result in any residual weakness. © 2016 Elsevier Inc. All rights reserved.
1. Introduction Stiff-person syndrome (SPS) is a rare neurological condition with unknown incidence and prevalence. It is a progressive disorder of muscle rigidity and painful muscle spasticity primarily affecting muscles of the spine, abdomen, and lower extremities. The primary cause is thought to be due to high titers of antibodies against glutamic acid decarboxylase, the rate-limiting enzyme for synthesis of γ-aminobutyric acid (GABA). As a result, patients with SPS have reduced production of GABA and increased spasticity and rigidity secondary to unopposed excitatory neuronal stimulation [1,2]. Although the exact etiology is unknown, SPS is believed to be autoimmune in origin, and it has been
☆
Disclosures: funding: n/a. ⁎ Corresponding author. Tel.: +1 412 360 1605; fax: +1 412 360 6906. E-mail addresses: [email protected] (J.M. Cassavaugh), [email protected] (T.M. Oravitz). http://dx.doi.org/10.1016/j.jclinane.2016.02.003 0952-8180/© 2016 Elsevier Inc. All rights reserved.
associated with other autoimmune disorders such as thyroiditis, vitiligo, and diabetes [1]. γ-Aminobutyric acid signaling has repeatedly been shown to have a role in many aspects of general anesthesia, including hypnosis, amnesia, and suppression of spinal reflexes. Previous studies have shown that volatile agents potentiate GABA signaling, as well as prolong the GABA-mediated synaptic inhibition [3]. The specific effects of volatile agents on patients with SPS are unknown. It has been proposed that their use may lead to prolonged weakness, especially in patients treated chronically with baclofen [4,5]. On the other hand, because of their action on the GABA pathway, many commonly used intravenous anesthetic medications have been shown to be beneficial for SPS. For example, benzodiazepines are commonly used to treat the associated spasticity, and currently, propofol is used as a bridge therapy before intravenous immunoglobulin in selective cases [6,7]. Conflicting reports exist regarding use of neuromuscular blockade, with several observing weakness severe enough to require prolonged intubation and intensive care unit admission and other studies reporting no prolonged weakness with their use. This report aims to
198 describe uncomplicated use of skeletal muscle relaxants in a patient with SPS. Permission for publication and informed written consent were obtained from the patient.
2. Case description A 45-year-old woman with a medical history significant for hypertension and hyperlipidemia presented for 3 separate general anesthetics within 2 years. She had no known allergies and no previous anesthetic complications. The initial case was performed before her diagnosis of SPS. At that time, she was undergoing workup for multiple sclerosis, as many of the presenting symptoms, including spasticity, are similar to symptoms of SPS. She was taking baclofen, hydrocodone, and 2 antihypertensive medications. The first procedure was a total thyroidectomy. Patient weight at time of total thyroidectomy was 107 kg, with a height of 165 cm. No muscle relaxants were used at induction; the thyroid lesion was causing tracheal displacement, and the airway was secured via awake fiberoptic bronchoscopy. Before the intubation, the patient received airway topicalization with nebulized lidocaine; lidocaine pledgets; and, with visualization of the vocal cords, direct topicalization of the trachea with 4% lidocaine. Her only sedation before induction was midazolam 2 mg. The neural integrity monitor electromyogram endotracheal tube was used during this case for laryngeal nerve monitoring, and therefore, neuromuscular blockade was withheld for the entirety of the case. Anesthesia was maintained with sevoflurane, and she received a total of propofol 200 mg and fentanyl 350 μg. There were no postoperative anesthesia complications. About 1 month before her next surgical procedure, the diagnosis of SPS had been established. This was primarily based on her symptoms, which began with bilateral lower extremity stiffness, weakness, and spasticity, which had led to several falls before the patient began using a walker. She also experienced significant left arm and shoulder stiffness, weakness, and decreased range of motion. The patient had a marked elevated anti–glutamic acid decarboxylase antibody level of 167.4 (reference range, 0-1.5). During this time, her SPS symptoms were controlled with various medications, including diazepam and tizapidine. She underwent a laparoscopic cholecystectomy 6 months after the thyroidectomy. Patient weight at the time of laparoscopic cholecystectomy was 108 kg. Induction for this procedure included succinylcholine (100 mg), and she received rocuronium 45 mg during the case, which lasted a total of 147 minutes. Sevoflurane was again used for maintenance of general anesthesia, along with a total of midazolam 2 mg, propofol 220 mg, and fentanyl 250 μg. Muscle relaxants were dosed, and train-of-4 (TOF) monitoring of the ulnar nerve was used (Table). Neostigmine (4 mg) was given for neuromuscular reversal, and she was extubated without any complications. Following the cholecystectomy, she experienced significant postoperative nausea and vomiting (PONV).
J.M. Cassavaugh and T.M. Oravitz Table
Neuromuscular monitoring using peripheral nerve stimulator. TOF 1
Time A. Cholecystectomy 10:25 10:45 11:05 11:25 B. Hysterectomy 9:40 9:50 10:15 post tetanic 10:35 10:45 11:00 11:17 11:35 1
4/4 4/4 4/4 4/4
Patient weight: 108 kg Rocuronium 45 mg Neostigmine 4 mg TOF monitoring site: ulnar, left
0/4 0/4
Patient weight: 104 kg Rocuronium 140 mg Neostigmine 4 mg TOF monitoring site: facial, left
4/4 1/4 4/4 2/4 4/4
TOF: Train of Four.
Twenty months later, the third procedure, a hysterectomy, was performed. Patient weight at time of laparoscopic-assisted vaginal hysterectomy was 104 kg. At this time, she was still taking diazepam, but she was also receiving intravenous immunoglobulin therapy. Again, succinylcholine (130 mg) was used for induction, and rocuronium (140 mg) was administered throughout the 209-minute case. Total intravenous anesthesia was used because of the previous PONV occurrence with primarily propofol infusion for maintenance, along with midazolam 2 mg and fentanyl 100 μg. Muscle relaxants were dosed, and TOF monitoring of the facial nerve was used (Table). Neostigmine (4 mg) was administered for residual neuromuscular blockade. She experienced no postoperative anesthesia complications.
3. Discussion Very limited data exists regarding anesthesia in patients with SPS, which is in part due to the extremely low incidence of the disease. Because of conflicting results in the few reports published, it has been difficult to establish the safest and most beneficial anesthesia plan for a patient with SPS. For patients with SPS, the literature is sparse and conflicting on the use of neuromuscular blocking agents. Previously, Obara et al [8] demonstrated safe use of vecuronium on several separate procedures in the same patient. However, Johnson and Miller [4] published contradictory data. In their report, the patient also received vecuronium and, despite the presence of 4 twitches and full reversal, required intubation overnight due to significant residual weakness. Pancuronium has also been evaluated in a case report describing cardiac surgery on a patient with SPS; Ferrandis et al [9] found normal return of TOF after the first dose of pancuronium but prolonged recovery following a second dose. It is unclear if the residual weakness observed in the aforementioned studies was due to prolonged neuromuscular
General Anesthesia for Stiff-Person Syndrome blockade. In 3 studies (Bouw et al [5], Johnson and Miller [4], and Ferrandis et al [9]), a similar situation was observed— return of TOF with nerve stimulation but clinical weakness resulting in prolonged intubation. It is possible that this prolonged weakness is not due to neuromuscular blockade and instead is due to central weakness from the interaction either between the volatile agents and GABA receptors or from the volatile agents and other commonly used medications in SPS, such as baclofen or diazepam. The lack of objective data on the specific mechanism for the prolonged weakness is the primary reason to use caution when administering any anesthetic to a patient with SPS. The hypothesis that prolonged weakness following a general anesthetic may be a result of the interaction between the volatile agent and baclofen on GABA signaling has been proposed in several reports [4,5]. Likewise, Sugimura et al [10] demonstrated in a murine model a shortened onset and a prolonged effect of anesthesia with combination volatile agents and GABA mimetics, including baclofen. The patient discussed presently was taking baclofen at the time of her thyroidectomy, which was completed without neuromuscular blockade. She did not experience prolonged or excessive weakness throughout her recovery. Continued studies aimed at understanding the mechanisms of pharmacologic modulation of the GABA receptor, especially with multiple agents, will be necessary to determine the safety of medication combinations in patients with SPS requiring general anesthesia. This case report is the first to establish safe use of both nondepolarizing and depolarizing neuromuscular blockade in a patient with SPS. This patient tolerated succinylcholine and rocuronium on 2 separate occasions without prolonged weakness or worsened rigidity. In addition, she did not require prolonged ventilator support, and had no difficulty with extubation. In both cases with neuromuscular blockade, her muscular function recovered within a normal time frame and without complication. Several previous case reports have
199 similarly not observed negative effects from skeletal muscle relaxants and would advocate for the safe use of neuromuscular blocking drugs. However, others have advocated for omission of neuromuscular blockade in patients with SPS receiving general anesthesia until more is known about their specific interaction in these patients. Although more studies are required for a definitive answer to this question, this report clearly demonstrates no complication with use of both nondepolarizing and depolarizing muscle relaxants in a patient with SPS.
References [1] Murison B. Stiff-person syndrome. Neurologist 2004;10:131-7. [2] Piovano C, Piattelli M, Spina T, Iervese G, Bosco G. The stiff-person syndrome. Minerva Anestesiol 2002;68:861-5. [3] Nishikawa K, Harrison N. The actions of sevoflurane and desflurane on the γ-aminobutyric acid receptor type A: effects of TM2 mutations in the α and β subunits. Anesthesiology 2003;99:678-84. [4] Johnson J, Miller K. Anesthetic implications in stiff-person syndrome. Anesth Analg 1995;80:612-3. [5] Bouw J, Leendertse K, Tijssen, Marina AJ, Dzoljic M. Anesth Analg 2003;97:486-7. [6] Dayalu P, Teener J. Stiff person syndrome and other anti-GAD–associated neurologic disorders. Semin Neurol 2012;32:544-9. [7] Hattan E, Angle MR, Chalk C. Unexpected benefit of propofol in stiffperson syndrome. Neurology 2008;70:1641-2. [8] Obara M, Sawamura S, Chinzei M, Komatsu K, Hanaoka K. Anaesthetic management of a patient with stiff-person syndrome. Anaesthesia 2002; 57:511. [9] Ferrandis R, Belda J, Llau J, Belda C, Bahamonde J. Anesthesia for cardiac surgery on a patient with stiff person syndrome. J Cardiothorac Vasc Anesth 2005;19:370-2. [10] Sugimura M, Kitayama S, Morita K, Imai Y, Irifune M, Takarada T, et al. Effects of GABAergic agents on anesthesia induced by halothane, isoflurane, and thiamylal in mice. Pharmacol Biochem Behav 2002;72: 111-6.
Case Report
Multiple anesthetics for a patient with stiff-person syndrome☆ Jessica M. Cassavaugh MD, PhD, Todd M. Oravitz MD ⁎ University of Pittsburgh, VA Pittsburgh Healthcare System Anesthesia Service, Room 3N221B, University Dr C, Pittsburgh, PA, 15240, USA Received 9 March 2015; accepted 4 February 2016
Keywords: GABA signaling; Neuromuscular blockade; Stiff-person syndrome
Abstract Stiff-person syndrome is a progressive disease of muscle rigidity and spasticity due to a deficiency in the production of γ-aminobutyric acid. Because of the rarity of the condition, little is known about effects of anesthesia on patients with stiff-person syndrome. This report describes the clinical course for a single patient with stiff-person syndrome who received general anesthesia on 3 separate occasions. Her anesthetics included use of both neuromuscular blockade and volatile agents. Unlike several previous reports regarding anesthesia and stiff-person syndrome, the postoperative period for this patient did not require prolonged intubation or result in any residual weakness. © 2016 Elsevier Inc. All rights reserved.
1. Introduction Stiff-person syndrome (SPS) is a rare neurological condition with unknown incidence and prevalence. It is a progressive disorder of muscle rigidity and painful muscle spasticity primarily affecting muscles of the spine, abdomen, and lower extremities. The primary cause is thought to be due to high titers of antibodies against glutamic acid decarboxylase, the rate-limiting enzyme for synthesis of γ-aminobutyric acid (GABA). As a result, patients with SPS have reduced production of GABA and increased spasticity and rigidity secondary to unopposed excitatory neuronal stimulation [1,2]. Although the exact etiology is unknown, SPS is believed to be autoimmune in origin, and it has been
☆
Disclosures: funding: n/a. ⁎ Corresponding author. Tel.: +1 412 360 1605; fax: +1 412 360 6906. E-mail addresses: [email protected] (J.M. Cassavaugh), [email protected] (T.M. Oravitz). http://dx.doi.org/10.1016/j.jclinane.2016.02.003 0952-8180/© 2016 Elsevier Inc. All rights reserved.
associated with other autoimmune disorders such as thyroiditis, vitiligo, and diabetes [1]. γ-Aminobutyric acid signaling has repeatedly been shown to have a role in many aspects of general anesthesia, including hypnosis, amnesia, and suppression of spinal reflexes. Previous studies have shown that volatile agents potentiate GABA signaling, as well as prolong the GABA-mediated synaptic inhibition [3]. The specific effects of volatile agents on patients with SPS are unknown. It has been proposed that their use may lead to prolonged weakness, especially in patients treated chronically with baclofen [4,5]. On the other hand, because of their action on the GABA pathway, many commonly used intravenous anesthetic medications have been shown to be beneficial for SPS. For example, benzodiazepines are commonly used to treat the associated spasticity, and currently, propofol is used as a bridge therapy before intravenous immunoglobulin in selective cases [6,7]. Conflicting reports exist regarding use of neuromuscular blockade, with several observing weakness severe enough to require prolonged intubation and intensive care unit admission and other studies reporting no prolonged weakness with their use. This report aims to
198 describe uncomplicated use of skeletal muscle relaxants in a patient with SPS. Permission for publication and informed written consent were obtained from the patient.
2. Case description A 45-year-old woman with a medical history significant for hypertension and hyperlipidemia presented for 3 separate general anesthetics within 2 years. She had no known allergies and no previous anesthetic complications. The initial case was performed before her diagnosis of SPS. At that time, she was undergoing workup for multiple sclerosis, as many of the presenting symptoms, including spasticity, are similar to symptoms of SPS. She was taking baclofen, hydrocodone, and 2 antihypertensive medications. The first procedure was a total thyroidectomy. Patient weight at time of total thyroidectomy was 107 kg, with a height of 165 cm. No muscle relaxants were used at induction; the thyroid lesion was causing tracheal displacement, and the airway was secured via awake fiberoptic bronchoscopy. Before the intubation, the patient received airway topicalization with nebulized lidocaine; lidocaine pledgets; and, with visualization of the vocal cords, direct topicalization of the trachea with 4% lidocaine. Her only sedation before induction was midazolam 2 mg. The neural integrity monitor electromyogram endotracheal tube was used during this case for laryngeal nerve monitoring, and therefore, neuromuscular blockade was withheld for the entirety of the case. Anesthesia was maintained with sevoflurane, and she received a total of propofol 200 mg and fentanyl 350 μg. There were no postoperative anesthesia complications. About 1 month before her next surgical procedure, the diagnosis of SPS had been established. This was primarily based on her symptoms, which began with bilateral lower extremity stiffness, weakness, and spasticity, which had led to several falls before the patient began using a walker. She also experienced significant left arm and shoulder stiffness, weakness, and decreased range of motion. The patient had a marked elevated anti–glutamic acid decarboxylase antibody level of 167.4 (reference range, 0-1.5). During this time, her SPS symptoms were controlled with various medications, including diazepam and tizapidine. She underwent a laparoscopic cholecystectomy 6 months after the thyroidectomy. Patient weight at the time of laparoscopic cholecystectomy was 108 kg. Induction for this procedure included succinylcholine (100 mg), and she received rocuronium 45 mg during the case, which lasted a total of 147 minutes. Sevoflurane was again used for maintenance of general anesthesia, along with a total of midazolam 2 mg, propofol 220 mg, and fentanyl 250 μg. Muscle relaxants were dosed, and train-of-4 (TOF) monitoring of the ulnar nerve was used (Table). Neostigmine (4 mg) was given for neuromuscular reversal, and she was extubated without any complications. Following the cholecystectomy, she experienced significant postoperative nausea and vomiting (PONV).
J.M. Cassavaugh and T.M. Oravitz Table
Neuromuscular monitoring using peripheral nerve stimulator. TOF 1
Time A. Cholecystectomy 10:25 10:45 11:05 11:25 B. Hysterectomy 9:40 9:50 10:15 post tetanic 10:35 10:45 11:00 11:17 11:35 1
4/4 4/4 4/4 4/4
Patient weight: 108 kg Rocuronium 45 mg Neostigmine 4 mg TOF monitoring site: ulnar, left
0/4 0/4
Patient weight: 104 kg Rocuronium 140 mg Neostigmine 4 mg TOF monitoring site: facial, left
4/4 1/4 4/4 2/4 4/4
TOF: Train of Four.
Twenty months later, the third procedure, a hysterectomy, was performed. Patient weight at time of laparoscopic-assisted vaginal hysterectomy was 104 kg. At this time, she was still taking diazepam, but she was also receiving intravenous immunoglobulin therapy. Again, succinylcholine (130 mg) was used for induction, and rocuronium (140 mg) was administered throughout the 209-minute case. Total intravenous anesthesia was used because of the previous PONV occurrence with primarily propofol infusion for maintenance, along with midazolam 2 mg and fentanyl 100 μg. Muscle relaxants were dosed, and TOF monitoring of the facial nerve was used (Table). Neostigmine (4 mg) was administered for residual neuromuscular blockade. She experienced no postoperative anesthesia complications.
3. Discussion Very limited data exists regarding anesthesia in patients with SPS, which is in part due to the extremely low incidence of the disease. Because of conflicting results in the few reports published, it has been difficult to establish the safest and most beneficial anesthesia plan for a patient with SPS. For patients with SPS, the literature is sparse and conflicting on the use of neuromuscular blocking agents. Previously, Obara et al [8] demonstrated safe use of vecuronium on several separate procedures in the same patient. However, Johnson and Miller [4] published contradictory data. In their report, the patient also received vecuronium and, despite the presence of 4 twitches and full reversal, required intubation overnight due to significant residual weakness. Pancuronium has also been evaluated in a case report describing cardiac surgery on a patient with SPS; Ferrandis et al [9] found normal return of TOF after the first dose of pancuronium but prolonged recovery following a second dose. It is unclear if the residual weakness observed in the aforementioned studies was due to prolonged neuromuscular
General Anesthesia for Stiff-Person Syndrome blockade. In 3 studies (Bouw et al [5], Johnson and Miller [4], and Ferrandis et al [9]), a similar situation was observed— return of TOF with nerve stimulation but clinical weakness resulting in prolonged intubation. It is possible that this prolonged weakness is not due to neuromuscular blockade and instead is due to central weakness from the interaction either between the volatile agents and GABA receptors or from the volatile agents and other commonly used medications in SPS, such as baclofen or diazepam. The lack of objective data on the specific mechanism for the prolonged weakness is the primary reason to use caution when administering any anesthetic to a patient with SPS. The hypothesis that prolonged weakness following a general anesthetic may be a result of the interaction between the volatile agent and baclofen on GABA signaling has been proposed in several reports [4,5]. Likewise, Sugimura et al [10] demonstrated in a murine model a shortened onset and a prolonged effect of anesthesia with combination volatile agents and GABA mimetics, including baclofen. The patient discussed presently was taking baclofen at the time of her thyroidectomy, which was completed without neuromuscular blockade. She did not experience prolonged or excessive weakness throughout her recovery. Continued studies aimed at understanding the mechanisms of pharmacologic modulation of the GABA receptor, especially with multiple agents, will be necessary to determine the safety of medication combinations in patients with SPS requiring general anesthesia. This case report is the first to establish safe use of both nondepolarizing and depolarizing neuromuscular blockade in a patient with SPS. This patient tolerated succinylcholine and rocuronium on 2 separate occasions without prolonged weakness or worsened rigidity. In addition, she did not require prolonged ventilator support, and had no difficulty with extubation. In both cases with neuromuscular blockade, her muscular function recovered within a normal time frame and without complication. Several previous case reports have
199 similarly not observed negative effects from skeletal muscle relaxants and would advocate for the safe use of neuromuscular blocking drugs. However, others have advocated for omission of neuromuscular blockade in patients with SPS receiving general anesthesia until more is known about their specific interaction in these patients. Although more studies are required for a definitive answer to this question, this report clearly demonstrates no complication with use of both nondepolarizing and depolarizing muscle relaxants in a patient with SPS.
References [1] Murison B. Stiff-person syndrome. Neurologist 2004;10:131-7. [2] Piovano C, Piattelli M, Spina T, Iervese G, Bosco G. The stiff-person syndrome. Minerva Anestesiol 2002;68:861-5. [3] Nishikawa K, Harrison N. The actions of sevoflurane and desflurane on the γ-aminobutyric acid receptor type A: effects of TM2 mutations in the α and β subunits. Anesthesiology 2003;99:678-84. [4] Johnson J, Miller K. Anesthetic implications in stiff-person syndrome. Anesth Analg 1995;80:612-3. [5] Bouw J, Leendertse K, Tijssen, Marina AJ, Dzoljic M. Anesth Analg 2003;97:486-7. [6] Dayalu P, Teener J. Stiff person syndrome and other anti-GAD–associated neurologic disorders. Semin Neurol 2012;32:544-9. [7] Hattan E, Angle MR, Chalk C. Unexpected benefit of propofol in stiffperson syndrome. Neurology 2008;70:1641-2. [8] Obara M, Sawamura S, Chinzei M, Komatsu K, Hanaoka K. Anaesthetic management of a patient with stiff-person syndrome. Anaesthesia 2002; 57:511. [9] Ferrandis R, Belda J, Llau J, Belda C, Bahamonde J. Anesthesia for cardiac surgery on a patient with stiff person syndrome. J Cardiothorac Vasc Anesth 2005;19:370-2. [10] Sugimura M, Kitayama S, Morita K, Imai Y, Irifune M, Takarada T, et al. Effects of GABAergic agents on anesthesia induced by halothane, isoflurane, and thiamylal in mice. Pharmacol Biochem Behav 2002;72: 111-6.