Stiff Person Syndrome

Stiff Person Syndrome and Anesthesia: Case Report

1. Jans Bouw, MD*, 
2. Karin Leendertse, MD*, 
3. Marina A. J. Tijssen, MD PhD†and 
4. Misa Dzoljic, MD PhD*

+Author Affiliations

1. *Departments of Anesthesiology and †Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

1. Address correspondence and reprint requests to J. Bouw, MD, Department of Anesthesiology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. Address e-mail toj.bouw@amc.uva.nl.

 

Next Section

Abstract

IMPLICATIONS: This case report describes the successful perioperative management of a patient with a rare and disabling neurologic disorder, the stiff person syndrome. The patient had a delayed emergence despite apparent full reversal of neuromuscular blockade. We suggest an interaction between the GABAergic effects of baclofen and volatile anesthetics as a possible cause.

Stiff person syndrome (SPS) is a rare and disabling neurologic disorder characterized by muscle rigidity and episodic spasms that involve axial and limb musculature (1–3). The literature points toward an autoimmune disorder resulting in a malfunction of γ-aminobutyric acid (GABA)-mediated inhibitory networks in the central nervous system (4). Anesthetic implications are less well described. We report a case of prolonged hypotonicity after general anesthesia in a patient with SPS and discuss the possible anesthetic interactions.

Previous SectionNext Section

Case Report

A 62-yr-old woman (height, 1.70 m; weight, 61 kg) was scheduled for resection of a colon carcinoma. Her medical history revealed hypothyroidism, vitamin B12 deficiency, and SPS. This syndrome started with low back pain, which rendered her unable to walk. She was experiencing stiffness, involuntary jerks, and painful cramps. Neurological examination revealed extreme hypertonia of the body and proximal legs, with intercurrent, painful spasms. Reflexes were symmetrical without Babinski signs. Laboratory findings showed positive glutamic acid decarboxylase (GAD) and negative amphiphysin antibodies. The patient was successfully treated with baclofen and diazepam. Subsequently, prednisone as immunosuppressive therapy was started. The stiffness diminished, and the patient was able to walk unaided. The neurological examination was unremarkable, except for a slight stiffness in the legs. Her medication at admission was prednisone 20 mg once a day, baclophen 12.5 mg twice a day (daily dose = 25 mg), diazepam 7.5 mg twice a day (daily dose = 15 mg), levothyroxine 25 μg once a day, and vitamin B12 injections. Her medical history included urological and gynecological surgery under general anesthesia before she experienced SPS.

No premedication was given. Anesthesia was induced with propofol (2.5 mg/kg) and sufentanil (0.25 μg/kg). After the administration of atracurium (0.6 mg/kg), the trachea was intubated, and anesthesia was continued with isoflurane (0.6–1.0 vol%) and oxygen/air for the duration of the procedure. Cefuroxime 1500 mg, clindamycin 600 mg, and dexamethasone 10 mg were administered IV. In the following 2 h, additional atracurium (35 mg), sufentanil (10 μg), and morphine (8 mg) were administered. At the end of the procedure, which was uneventful, neuromuscular monitoring showed four strong twitches. Although the patient was responsive, she could not open her eyes, grasp with either hand, or generate tidal volumes beyond 200 mL. Neostigmine 2 mg (0.03 mg/kg) and glycopyrrolate 0.2 mg did not alter the clinical signs of muscle weakness.

The patient was sedated with propofol 5 mg · kg⁻¹ · h⁻¹ and further mechanically ventilated in the recovery room. After 1 h, the sedation was stopped and mechanical ventilation was terminated. At that time, baclofen 12.5 mg was administered into the gastric tube. Two hours later she was in a good clinical condition, and her trachea was extubated.

Previous SectionNext Section

Discussion

SPS was recognized as a distinct entity in 1956 by Moersch and Woltman (5). An autoimmune pathogenesis is suspected because of the presence of antibodies against GAD, the rate-limiting enzyme for synthesis of the inhibitory neurotransmitter GABA, and the association of the disease with other autoimmune conditions such as diabetes and thyroiditis (6,7). Loss of inhibition from higher centers causes hyperactivity of the γ-motor neuron system and subsequent progressive muscle rigidity. Patients with SPS have high immunoglobulin G/anti-GAD-65 antibodies, which are synthesized intrathecally and seem to impair the in situ synthesis of GABA (8,9). Two types of drugs have been applied: drugs that enhance GABA activity and immunosuppressing drugs. Diazepam, which increases the frequency of opening of the GABA_A receptor and leads to hyperpolarization, is the initial treatment of choice at daily doses up to 200 mg. Intrathecal or oral baclofen may improve the physical symptoms just like prednisone, plasmapheresis, and large-dose IV immunoglobulin (10).

In our case, several drugs could have caused muscle weakness (11). Initially atracurium could be suspected. Computer-simulated pharmacokinetic analyses suggested that plasma concentrations were far less than therapeutic levels. The same can be said for opioids, fentanyl, and morphine (Fig. 1) (12–15). In the recovery room while the patient was still ventilated, it showed a diazepam serum concentration of 0.317 mg/L (therapeutic range, 0.125–0.75 mg/L). Because IV drugs can be excluded as causing muscular weakness, perhaps volatile anesthetics were the cause. In the case report by Johnson and Miller (10), muscle weakness was observed only when baclofen was combined with inhaled desflurane or isoflurane. Delayed arousal and muscle weakness were also described, unrelated to SPS, in a patient receiving baclofen and undergoing anesthesia with isoflurane 1% (16). In addition, recent animal studies show that baclofen enhances volatile anesthetic-induced anesthesia (17). Perhaps the complicated course of recovery was most due to the interaction between isoflurane and baclofen causing muscle weakness.

View larger version:

• In this page
 
• In a new window

• Download as PowerPoint Slide

Figure 1. Chart showing three different drugs given during the procedure. Time 0 represents the start of the procedure, which ended after 150 min. The serum concentrations of sufentanil and atracurium, although given in different units, can be seen on the left axis, and the right axis represents serum concentrations of morphine. It is noteworthy that after the initial intubation dose of atracurium, three doses (5, 10, and 20 mg) were given during the procedure.

Previous SectionNext Section

We thus conclude that the prolonged muscle relaxation can be explained by the enhancement of general anesthetics via GABA_B action on synaptic transmission (17). This case demonstrates a potential danger in combining baclofen with volatile anesthetics in patients with SPS.

Previous SectionNext Sectio

ANAESTHESIA FOR DAY SURGERY

THE HONG KONG COLLEGE OF ANAESTHESIOLOGISTS P5 February 1993

Reviewed Feb 2002

GUIDELINES FOR DAY CASE SURGERY

GUIDELINES ON ANAESTHESIA FOR DAY SURGERY

1. GENERAL COMMENTS

Safety of anaesthesia must not be compromised by financial or other expediency,

to the detriment of those who, by definition, are fitter than the majority of the

population.

2. FACTORS AFFECTING CHOICE OF PATIENT

2.1 Patients should be ASA (American Society of Anaesthesiologists) grade I or II. Exceptionally ASA grade III may be accepted.

2.2 Children, (who should be over six months of age), must be accompanied by parents/guardians at all relevant times.

2.3 Patients should reside within easy access to the surgical facility.

3. PREANAESTHETIC ASSESSMENT

3.1 Every patient must have a preanaesthetic assessment by an anaesthesiologist, preferably by the one who will administer the anaesthetic.

3.2 This assessment may be made in a hospital, clinic or in the day case centre.

3.3 When appropriate, the results of investigations, eg. chest X-ray, electrocardiogram, serum electrolyte and urea concentrations, and urinalysis, must be available to the assessing anaesthesiologist.

3.4 Acceptance for day case anaesthesia should be refused if the patient is unfit, appropriate medical information is lacking or the likelihood of complications is high.

4. PREANAESTHETIC INSTRUCTIONS

4.1 Proforma should be prepared to advise the patient/guardian of details about fasting time, reporting time and admission procedures.

4.2 In the case of a minor, a parent/guardian must accompany the patient to elaborate, if necessary, on the medical history (vide 3.1), and provide assistance, if required during induction and/or recovery.

4.3 Signed consent for the proposed procedure must be obtained from the patient or guardian and a preoperative leaflet discussed and handed out.

5. STAFFING

5.1 The anaesthesiologist must be provided with a dedicated and appropriately trained assistant.

5.2 There must be adequate assistance for the transporting and positioning of patients.

5.3 A qualified anaesthesiologist should be immediately available when anaesthesia is given by a trainee.

6. FACILITIES

6.1 The day surgery centre must have facilities which conform with the guidelines issued by the College, in particular :-

Recommended minimum facilities for safe anaesthetic practice in operating suites (T2).

Guidelines for monitoring in anaesthesia (P1).

Guidelines for postanaesthetic recovery care (P3).

6.2 Easy access to transport facilities is important.

7. SURGICAL CASE SELECTION

7.1 The scope and nature of surgery must be agreed by the surgeon and anaesthesiologist responsible for the day surgery in the centre.

7.2 Patients who might require blood transfusion, suffer excessive postoperative discomfort, or who are unlikely to be fit to be discharged home on the same day, are unsuitable for day surgery.

7.3 Patients living in single accommodation or who are unable to provide a responsible person to oversee their welfare for the first 24 hours cannot be accepted for day surgery.

8. POSTOPERATIVE RECOVERY

8.1 Patients must be observed and recovered by appropriately trained staff prior to discharge.

8.2 There should be a record of recovery to include conscious state, orientation,

sensory and motor function (including locomotion), pulse rate, blood pressure, and any postoperative pain.

9. DISCHARGE

9.1 Verbal and written instructions must be given to the patient and/or guardian prior to discharge with particular reference to :-

9.1.1 Immediate action in the event of complications, and

9.1.2 Whom to contact (with telephone number).

9.2 The patient must be advised verbally and in writing, that, in the first 24 hours

postoperatively, he/she must NOT :-

9.2.1 Drive or operate machinery.

9.2.2 Cook.

9.2.3 Work or make important decisions.

9.2.4 Drink alcohol.

9.2.5 Take any medication except that approved by the day case centre.

9.3 The patient must be escorted home by a responsible adult by private transport. In

the case of a minor, the responsible person attending the child during transport

should not be the driver.

9.4 If the discharge criteria are not met, the patient must be admitted.

9.5 The anaesthesiologist who gave the anaesthetic, in conjunction with the operator

and the nursing officer in charge of the day case centre, is responsible for the

discharge of the patient in accordance with agreed protocols.

view from Tahrir square

Peripheral Nerve Stimulation

Peripheral Nerve Stimulation

Indications

Because of the variation in patient sensitivity to neuromuscular blocking agents, the neuromuscular function of all patients receiving intermediate- or long-acting neuromuscular blocking agents should be monitored. In addition, peripheral nerve stimulation is helpful in assessing paralysis during rapid-sequence inductions or during continuous infusions of short-acting agents. Furthermore, peripheral nerve stimulators can help locate nerves to be blocked by regional anesthesia.

Contraindications

There are no contraindications to neuromuscular monitoring, although certain sites may be precluded by the surgical procedure.

Techniques & Complications

A peripheral nerve stimulator delivers a current of variable frequency and amplitude to a pair of either ECG silver chloride pads or subcutaneous needles placed over a peripheral motor nerve. The evoked mechanical or electrical response of the innervated muscle is observed. Although electromyography provides a fast, accurate, and quantitative measure of neuromuscular transmission, visual or tactile observation of muscle contraction is usually relied upon in clinical practice. Ulnar nerve stimulation of the adductor pollicis muscle and facial nerve stimulation of the orbicularis oculi are most commonly monitored. Because it is the inhibition of the neuromuscular receptor that needs to be monitored, direct stimulation of muscle should be avoided by placing electrodes over the course of the nerve and not over the muscle itself. To deliver a supramaximal stimulation to the underlying nerve, peripheral nerve stimulators must be capable of generating at least a 50-mA current across a 1000- load. This current is uncomfortable for a conscious patient. Complications of nerve stimulation are limited to skin irritation and abrasion at the site of electrode attachment.

Succinylcholine

Succinylcholine Should Be Avoided in Patients on Statin Therapy

Lee, Chingmuh M.D.

Author Information

David Geffen School of Medicine, University of California, Los Angeles, Harbor-UCLA Medical Center, Department of Anesthesiology, Torrance, California. chingleeucla@ucla.edu

Photograph: J. P. Rathmell.

Accepted for publication April 4, 2011. The author has, in the past, received sponsorship (Burroughs Wellcome & Company, Research Triangle Park, North Carolina, and Organon USA Inc., Orange, New Jersey) for laboratory and clinical studies on various neuromuscular blocking and reversal agents, including TAAC3 and sugammadex. He has no current or future financial interest in the topic of this article or any drugs mentioned.

This article has been selected for the Anesthesiology CME Program. Learning objectives and disclosure and ordering information can be found in the CME section at the front of this issue.

This Editorial View accompanies the following article: Turan A, Mendoza ML, Gupta S, You J, Gottlieb A, Chu W, Saager L, Sessler DI: Consequences of succinylcholine administration to patients using statins. Anesthesiology 2011; 115:28–35.

PARAPHRASING that an old soldier never dies, he just fades away, this author has written of succinylcholine, “A drug capable of generating so many controversies, surviving so many crises, so uniquely short acting and rapid in onset, and inexpensive, will not just die.”¹ Indeed, succinylcholine still invites attention. In this issue of Anesthesiology, Turan et al. skillfully document that patients who were receiving statin medications for hypercholesterolemia had greater myoglobinemia and fasciculation after intravenous administration of 1.5 mg/kg succinylcholine than did similar patients not taking statin medications.² Because the myoglobinemia remained well below its normal renal toxicity threshold, the authors suggested that the muscular injury probably is of limited clinical consequences. Nevertheless, this new finding should provoke a timely reassessment of the role of succinylcholine.

First of all, quantification of the succinylcholine-statin interaction is timely and important, considering the widespread, ever-increasing use of statin drugs in our health-conscious aging population and considering that both succinylcholine and the statin drugs frequently cause muscle damage.²

Turan et al. appropriately excluded from their study patients with American Society of Anesthesiologists status greater than III and those undergoing orthopedic and spinal surgeries and surgeries involving extensive muscle manipulations. They also excluded patients with hepatic, renal, or neuromuscular pathologies and those with chronic pain and risk of malignant hyperthermia.² I have no qualms with a conclusion that absent other concerns, statin therapy per semay not necessarily contraindicate succinylcholine. I am, however, concerned with patients disqualified from this study, especially the vulnerable seniors with reduced functional reserves. Other unanswered questions remain because statins vary in their propensity to cause muscle damage, and patients vary in their existing muscle damage and in the succinylcholine interaction.

Indications for succinylcholine, or any drug, must be reevaluated periodically as more is learned about it. When they introduced succinylcholine to the United States 59 yr ago, Foldes et al.concluded in their 1952 publication that succinylcholine approximated most closely the definition of ideal relaxant.³ Upon reevaluation, however, Savarese and Kitz⁴ called for a major effort to replace succinylcholine with a “nondepolarizing succinylcholine,” and Savareseet al.⁵ immediately launched that effort in 1975. Lee classified the disadvantages of succinylcholine and noted that the list kept growing, whereas the drug's specific indications kept dwindling.⁶ Many short-acting compounds intended to replace succinylcholine, including rapacuronium and TAAC3, have proved promising. Unfortunately, none have succeeded.^7–9 Vecuronium, rocuronium, and cisatracurium excelled on their own virtues and gained wide clinical acceptance, but they also failed to completely retire succinylcholine. Currently, the rocuronium-sugammadex combination beats succinylcholine in practically all outcome measures.⁸ Unfortunately, sugammadex is still unavailable in the United States. Another series of compounds, the CW002-related neuromuscular blocking agents, are promising but remain experimental.^10,11 Meanwhile, the advantages and disadvantages of succinylcholine and its indications should be updated in light of the current study by Turan et al.

Economic reality requires all healthcare providers to be cost-conscious, and succinylcholine is indeed inexpensive. However, the cost of a drug must be evaluated in proper context. Mind the dollar and the penny will take care of itself. A Duke University study showed that American patients were willing to pay $33 out of pocket to avoid succinylcholine myalgia.¹² This finding alone should go a long way toward paying for an intubation dose of a replacement nondepolarizing relaxant at less than $10. Besides myalgia, how much would an informed consumer pay to avoid sinus arrest, catecholamine release, the possibility of masseter spasm,¹³ chances of prolonged paralysis and malignant hyperthermia, fasciculation and increased oxygen consumption, and accelerated oxygen desaturation in the event of ventilatory failure and apnea?¹⁴ On balance, it appears penny-wise to deny patients an intubation dose of a nondepolarizing relaxant, which is also inexpensive relative to the statin drugs and other healthcare costs these patients face. After all, many inexpensive drugs have been removed from anesthesia practice; why not succinylcholine? In addition, the cost advantage of succinylcholine will be diluted if a nondepolarizing relaxant is administered soon afterward and if the cost is compared on a per minute basis. Admittedly, succinylcholine, at less than $2 an intubation dose, could be the only relaxant affordable in geographic areas of extreme low cost of living.

Are there indications for which succinylcholine is irreplaceable? One is obvious. In patients with unbreakable laryngospasm but no intravenous access (mostly pediatric), succinylcholine is uniquely advantageous. Its intramuscular injection could be lifesaving. However, I cannot tell how often this situation is unpreventable and how often an intravenous line cannot be established quickly at the first sign of trouble. In addition, succinylcholine remains popular in rapid-sequence intubation. This is significant because the full-stomach precaution is being applied quite liberally to many patients nowadays. Furthermore, for procedures of short duration, succinylcholine can provide profound relaxation to the last minute while still allowing rapid spontaneous recovery to occur. Finally, in the cannot-intubate-cannot-ventilate scenario, succinylcholine allows a chance for spontaneous breathing to return before serious harms ensue. These advantages of succinylcholine based on rapid recovery will diminish when sugammadex becomes available to encapsulate rocuronium or vecuronium in a “rescue reversal,”⁷ a situation for which the high cost of sugammadex is justifiable.

Compare succinylcholine with thiopental, another drug of great historic importance. They grew popular together and for decades were routinely found together on anesthesia carts and in stock rooms in large quantities. Both have benefitted millions and millions of patients for decades. Both feature rapid onset, speedy recovery from induction dose, cumulation on further use, and low cost. However, succinylcholine has more disadvantages and more serious side effects. After all, it is structurally, conformationally, and functionally two molecules of acetylcholine joined end on end, and therefore a nicotinic compound with predictable poor specificity as relaxant.¹Amazingly, years after the obsolescence of thiopental, succinylcholine is still used electively in more than a few hospitals.

A Chinese proverb states, “Spare no virtue even if minor, do no harm even if trivial.” We owe this duty to our patients, as soon as the risk/benefit and the cost/benefit ratios so indicate. Considering the great number of patients receiving statin therapy and the prevalence of muscle injury, no additional harm of succinylcholine is trivial to the society. In conclusion, succinylcholine still has a few indications based on specific advantages. Its ultimate fate in anesthesia will not be clear until clinicians gain experience with sugammadex. Meanwhile, it should be avoided in patients receiving statin therapy, unless specifically indicated.

Chingmuh Lee, M.D.

Figure. ... advantag...
Image Tools

David Geffen School of Medicine, University of California, Los Angeles, Harbor-UCLA Medical Center, Department of Anesthesiology, Torrance, California. chingleeucla@ucla.edu