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Anesth Analg 2004;99:593-594
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000123011.00161.C9

REGIONAL ANESTHESIA

Seizures After a Bier Block with Clonidine and Lidocaine

Shihab U. Ahmed, MB BS, MPH, Ricardo Vallejo, MD PhD, and E. Daniela Hord, MD

Massachusetts General Hospital Pain Center, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Shihab U. Ahmed, MD, Massachusetts General Hospital Pain Center, WACC-324, Massachusetts General Hospital, 15 Parkman St., Boston, MA 02114. Address e-mail to sahmed{at}partners.org


   Abstract
Top
 Abstract
Introduction
 Case Report
 Discussion
 References
 
A 47-yr-old man with history of complex regional pain syndrome type 1 underwent an IV Bier block with a mixture of lidocaine and clonidine. The tourniquet was deflated after 60 min, and approximately 10 min later he presented with complex partial seizures. The possible mechanisms for this are discussed, and the effects of clonidine, lidocaine, and the mixture of both are reviewed, as are four additional published cases reporting seizures after the administration of clonidine.

IMPLICATIONS: Clonidine is being used increasingly as an adjuvant medication for neuropathic pain and to improve the duration of regional anesthesia. Four cases of seizures associated with the use of clonidine have been reported. We present a case of seizure after a Bier block with lidocaine and clonidine in a patient with complex regional pain syndrome type I.


   Introduction
Top
 Abstract
 Introduction
Case Report
 Discussion
 References
 
In 1908, August Bier first described IV regional neural block with procaine. Years later (1974), Hannington-Kiff (1) used the same technique for IV regional sympathetic block with guanethidine sulfate. Since then, various other drugs have been used to produce sympatholysis, including bretylium, labetalol, phentolamine, clonidine, and lidocaine. Clonidine, an {alpha}2-receptor agonist, reduces hyperalgesia when injected subcutaneously. The local anesthetic lidocaine is often administered IV for various neuropathic pain conditions. Early, inadvertent, release of the tourniquet during Bier block with lidocaine can cause systemic toxicity, including seizures, from transiently high plasma levels.

In this report, we present a case in which we performed a Bier block with a mixture of lidocaine and clonidine for complex regional pain syndrome type 1. Sixty minutes after injection of the medications, the tourniquet was released, 10 min after which the patient developed seizures.


   Case Report
Top
 Abstract
 Introduction
 Case Report
Discussion
 References
 
A 47-yr-old man with left distal upper extremity complex regional pain syndrome type 1 was scheduled for a Bier block. Prior pain therapy included a stellate ganglion block with minimal pain relief and resection of a suspected neuroma, which yielded no improvement. The patient had been taking gabapentin 3600 mg/d and nortriptyline 100 mg/d with minimal benefit. He denied any history of seizure disorder, head trauma, or alcohol or recreational drug use. Routine monitors included a blood pressure cuff, electrocardiogram leads, and pulse oximeter probe. Two separate IV lines were placed. The limb was elevated for 5 min, and the tourniquet was inflated at 250 mm Hg around the arm. We slowly injected 20 mL of solution containing 150 mg of lidocaine (1.5%) and 30 µg of clonidine via IV catheter. Approximately 15 min later, the patient described numbness in his forearm, but with persistent burning pain. Because of the pain, the tourniquet was kept inflated an additional 20 min (for a total of 60 min) and then gradually deflated. His vital signs were stable throughout the procedure and after tourniquet deflation.

Approximately 10 min after the deflation of the tourniquet, the patient complained of "not feeling well" and had rhythmic clonic movements of the upper and lower extremities for approximately 30 s, accompanied by altered consciousness and vocal automatism. He was given propofol 30 mg IV. He was breathing spontaneously but appeared to be postictal and confused, so he was given supplemental oxygen via face mask. His vital signs remained stable. During the next 2 h, he had 5 similar episodes without fully regaining clear sensorium (orientation to place and person) between episodes. The episodes were interpreted as complex partial seizures; the patient experienced aura, automatism, rhythmic jerking of the extremities, and tonic deviation of the eyes associated with impairment of consciousness without complete loss of consciousness. He was given propofol 30 mg IV for each episode. He also received 5 mg of diazepam after the first episode and another 5 mg after the fourth episode of seizure. He was escorted to the emergency room and had a head computed tomography scan, which was negative. The blood chemistry (2.5 h after tourniquet release) showed lidocaine (0.62 µg/mL) and benzodiazepine, without any illicit drugs. He was admitted for overnight observation. Four hours after the first seizure, he became fully alert and oriented but was unable to recall events after the IV infusions were started. He had an uneventful night and was discharged home on his second hospital day without recurrence of seizures.


   Discussion
Top
 Abstract
 Introduction
 Case Report
 Discussion
References
 
Lidocaine decreases neuronal excitability by blocking voltage-gated sodium channels. At small concentrations, it has an antiepileptic effect and may be used as a treatment for status epilepticus (2). At large concentrations, it causes cortical hyperstimulation related to selective depression of inhibitory cortical synapses and neurons (3). Serum concentrations larger than 15 µg/mL often result in seizures in humans and laboratory animals (4). The lidocaine metabolites monoethylglycinexylidide and, to a lesser extent, 2,6-glycine xylidide can also decrease the seizure threshold. In animals, the monoethylglycinexylidide serum level that correlated with seizures was 4–6 µg/mL (5). In general, seizures induced by lidocaine under experimental conditions begin in the amygdala (4) or elsewhere in the limbic system (6) and are tonic-clonic in nature (4). However, complex partial seizures related to lidocaine have been reported (7).

Clonidine has many clinical uses, including treatment of hypertension, evaluation of growth hormone reserve, and differentiation of Parkinson’s disease from multiple system atrophy. It is also used as an adjuvant in combination with opioids and local anesthetics for regional anesthesia and is prescribed in oral and transdermal formulations for neuropathic pain. Research suggests that clonidine suppresses central noradrenergic activity (8) by inhibiting the excitatory amino acid pathway (9) or by depleting norepinephrine (10). The interaction between norepinephrine and seizure susceptibility is not completely understood. It has been suggested that norepinephrine acts as an anticonvulsant, possibly via augmentation of inhibitory {gamma}-aminobutyric acid effects (11). By reducing the norepinephrine available in central structures, mainly the locus caeruleus, clonidine might decrease the seizure threshold.

Four cases of seizure after clonidine administration have been reported: 1) accidental clonidine ingestion in a young child, followed by complex partial seizures (12); 2) oral clonidine administration to a hypoglycemic patient (13); 3) oral clonidine test for evaluation of growth hormone reserve in a preadolescent, followed by a generalized tonic-clonic seizure (14); and 4) oral clonidine given as premedication before methohexital spike provocation for video electroencephalograph monitoring in a patient with a history of complex partial seizures (15). In the last case, the maximum spike frequency with mirror focus was found in the 10-minute recordings before the application of methohexital and 90 minutes after the ingestion of clonidine. This patient also had two complex partial seizures before being given methohexital.

In cats, pretreatment with 5-hydroxytryptophan increases susceptibility to lidocaine-induced seizures (16). Therefore, medication that increases central nervous system (CNS) levels of serotonin has the potential to decrease the seizure threshold. Notably, our patient was taking nortriptyline.

This is the first case of seizure after Bier block with clonidine and lidocaine. Both lidocaine and clonidine have potential epileptogenic effects, as described above, and the two might be synergistic in decreasing the seizure threshold in the amygdala and limbic system. By increasing the CNS serotonin level, the tricyclic antidepressant nortriptyline may have contributed to the reduction in seizure threshold.


   References
Top
 Abstract
 Introduction
 Case Report
 Discussion
 References
 

  1. Hannington-Kiff JG. Intravenous regional sympathetic block with guanethidine. Lancet 1974; 1: 1019–20.[Medline]
  2. Pascual J, Sedano MJ, Polo JM, et al. Intravenous lidocaine for status epilepticus. Epilepsia 1986; 29: 584–9.
  3. Tanaka K, Yamasaki M. Blocking action of cortical inhibitory synapses by intravenous lidocaine. Nature 1966; 209: 207–8.[Medline]
  4. DeToledo JC. Lidocaine and seizures. Drug Monit 2000; 22: 320–2.
  5. Momota Y, Artru AA, Powers KM, et al. Concentrations of lidocaine and monoethylglycine xylidide in brain, CSF and plasma during lidocaine induced epileptiform electroencephalogram activity in rabbits: the effects of epinephrine and hypocapnia. Anesth Analg 2000; 91: 362–8.[Abstract/Free Full Text]
  6. Ingvar M, Shapiro HM. Selective metabolic activation of the hippocampus during lidocaine induced pre-seizure activity. Anesthesiology 1981; 54: 33–7.[ISI][Medline]
  7. De Jong RH, Walts LF. Lidocaine-induced psychomotor seizures in man. Acta Anaesthesiol Scand Suppl 1966; 23: 598–604.[Medline]
  8. Drew GM, Gower AJ, Marriot A. Alpha2-adrenoreceptors mediate clonidine induced sedation in the rat. Br J Pharmacol 1979; 67: 133–41.[ISI][Medline]
  9. Duggan S, Hong M, Milne B, et al. The role of excitatory amino acids in the expression of precipitated acute and chronic clonidine withdrawal: an in vivo volumetric study in the rat locus coeruleus. Brain Res 1994; 665: 253–61.[ISI][Medline]
  10. Grant SJ, Redmond DE Jr. The neuroanatomy and pharmacology of the nucleus locus coeruleus. Prog Clin Biol Res 1981; 71: 5–27.[Medline]
  11. Cheun JE, Yeh HH. Modulation of GABAA receptor-activated current by norepinephrine in cerebellar Purkinje cells. Neuroscience 1992; 51: 951–60.[ISI][Medline]
  12. MacFaul R, Miller G. Clonidine poisoning in children. Lancet 1977; 11: 1266–7.
  13. Shridar GR. Hypoglycemia due to sedation following clonidine test for growth hormone reserve. Clin Pediatr 1993; 32: 688–9.
  14. Scarramuzza A, Torresani P, Arisi D, et al. Seizures following clonidine test for growth hormone reserve: unusual presentation of benign partial epilepsy. J Pediatr Endocrinol Metab 2000; 13: 451–2.[ISI][Medline]
  15. Schmitt H, Druschky K, Hummel C, et al. Detection of an antiepileptic mirror focuses after oral application of clonidine. Br J Anaesth 1999; 83: 349–51.[Abstract/Free Full Text]
  16. DeOliveira LF, Heavner JE, de Jong RH. 5-Hydroxytryptophan intensifies local anesthetic-induced convulsions. Arch Int Pharmacodyn Ther 1974; 207: 333–9.[ISI][Medline]
Accepted for publication January 30, 2004.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press