CASE REPORT chloral hydrate, status epilepticus

Chloral Hydrate in Intractable Status Epilepticus

Five adult patients were admit ted to the neurological department in a state of status epilepticus. All were treated unsuccessfully wi th IV di- azepam and diphenylhydantoin. Administration of sodium valporate or phenobarbital also was ineffective. However, after treatment with intra- rectal chloral hydrate, all seizures ceased. The excellent effect of this drug was proved both clinically and electrodiagnostically. Discussed is the pos- sibility of using chloral hydrate to treat patients with status epilepticus in whom conventional treatment has failed. Lampl Y, Eshel Y, Gilad R, Sa- rova-Pinchas I: Chloral hydrate in intractable status epilepticus. Ann Emerg Med June 1990;19:674-676.]

I N T R O D U C T I O N Chloral hydrate is a hypnotic drug often used clinically for sedation and

sleep induction. Only a few reports, however, have described its use in treating status epilepticus in adults1, 2 and children. 3

Five patients suffering from status epilepticus were treated with chloral hydrate intrarectally after treatment with conventional medications had failed.

PATIENTS AND METHODS Five patients (four men and one woman aged 22 to 68 years) were hospi-

talized in a state of status epilepticus. The patients had five to 12 seizures within 30 minutes without returning to a normal alert state between the attacks. Patients' blood pressures ranged from 110/80 m m Hg to 185/100 m m Hg, and pulses ranged from 72 to 112. All five had spontaneous respi- rations at a rate of 12 to 38.

Each patient was treated with 20 mg diazepam IV at a rate of 2 rag/rain combined with 20 mg/kg diphenylhydantoin at a rate that did not exceed 50 mg/min.

The treatment failed in all cases. Thirty to 35 minutes after this treat- ment, three of the patients (2, 3, and 5) received an IV drip (5% glucose solution with 100 mg diazepam/500 mL) at 8 mg/hr. Two other patients (1 and 4) were given 20 mg/kg phenobarbital IV. Neither of the treatments stopped the seizures or reduced the number of convulsions. Diphenylhy- dantoin serum level was within effective range in each patient (Table). In two patients, a dose of 20 mg/kg intrarectal valporate proved unsuccessful.

Four of the patients had been on anticonvulsive medication before ad- mission (Table). In one patient (3), the treatment was discontinued a week before his admission. Another patient (2) had never suffered from any epi- leptic attacks before the present incident and had therefore not been treated.

Comprehensive blood tests were carried out in all patients during their hospitalization. Lumbar puncture was done in four of five patients (1 through 4). No evidence of infectious disease of the central nervous system or subarachnoid hemorrhage was found. In patient 5, lumbar puncture was not done because a space-occupying lesion with a massive mass effect was found by computed tomography (CT).

Repeated CT scan of the brain in all patients during the hospitalization demonstrated brain infarcts in two (1 and 2). The cerebral lesions were found in the right frontoparietal and temporal areas. In one patient (5),

Yair Lampl, MD Yechiel Eshel, MD, MSc Ronit Gilad, MD Ida Sarova-Pinchas, MD Holon and Tel Aviv, Israel

From the Department of Neurology, Edith Wolfson Medical Center, Holon, israel; and the Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel.

Received for publication July 6, 1989. Revision received January 10, 1990. Accepted for publication January 30, 1990.

Address for reprints: Yair Lampl, MD, Department of Neurology, Edith Wolfson Medical Center, Holon, Israel.

19:6 June 1990 Annals of Emergency Medicine 674/91

CHLORAL HYDRATE Lampl et al

TABLE. Clinical patient characteristics

Patient No./ Age (yr)

1/62

2/57

3/52

4/22

5/69

Previous Diseases

Recurrent cerebro- vascular accident

Tumor of lung with brain metastasis

Type of Epileptic Attack and Time of Occurrence

Generalized grand real and petit mal since childhood

No attacks before admission

Generalized grand mal since age 22 years

Generalized grand mal seizures since childhood

Simple partial seizures for past two months

Previous Medical Treatment

Carbazepin 600 mg/ day, ethosuximid

No therapy

*DPH 300 mg/day; discontinued a week before present attack

Carbazepin 600 mg/day

DPH 300 mg/day

Result of Brain CT

Right temporal lesion

Right frontoparietal lesion

No pathological findings

No pathological findings

Metastasis in left parietotemporal region

Present Medical Treatment

Diazepam, DPH, phenobarbital, chloral hydrate Diazepam, DPH, sodium valporate, chloral hydrate Diazepam, DPH, sodium valporate Diazepam, DPH, phenobarbital chloral hydrate Diazepam, DPH, chloral hydrate

*DPH, diphenylhydantion.

DPH Level In Blood Serum

19.5

21

16

17.5

17

Result of Chloral Hydrate Treatment

Seizure stopped after seven minutes Recurrent focal seizures

after eight, 14, and 21 hours Seizure stopped after five minutes

Seizure stopped after five minutes

Seizure stopped after five minutes

Seizure stopped after 12 minutes Recurrent seizure after

18 hours

cerebral metastasis in the left pari- etotemporal region was found. The pr imary site was diagnosed in the lung. In two patients (3 and 4), CT of the brain was normal.

In patients 2, 3, and 4 EEG record- ing was done 20, 40, and 55 minutes, respectively, after the last chloral hydrate administration.

All patients were treated with 30 mg/kg intrarectal chloral hydrate ev- ery two hours. Chloral hydrate treat- ment was initiated in four patients within 50 minutes after onset of sei- zures and, in one patient, 60 minutes after onset of seizures. In three pa- tients (2 through 4), the attacks corn-

pletely disappeared wi th in five to seven minutes. No new epileptic ac- t iv i ty was recorded by electroen- cephalography.

In one patient (1), three left focal seizures occurred eight, 14, and 21. hours after administration of chloral hydrate. In one pat ient (5), the at- tacks stopped after 12 minutes, but a single generalized seizure occurred more than 24 hours after treatment began. Six hours after the beginning of treatment, chloral hydrate was re- duced to 20 mg/kg every four hours for a to ta l t r e a t m e n t t ime of 48 hours.

Three of the patients (3 through 5)

Annals of Emergency Medicine

regained full consciousness and were discharged after several days. One pa- t ien t (2), who prev ious ly suffered from recurrent events of stroke, re- gained c o n s c i o u s n e s s and par t ia l functioning. After a week, there was a deterioration in his state of con- sciousness; on brain CT, an addi- tional extensive parietal lesion was revealed. The pa t ien t died a week later. During the ten days preceding his death, he did not develop new ep- ileptic seizures. One patient (1) did not regain consciousness despite the disappearance of epileptic activity. She died three weeks after admis- sion. An autopsy revealed a massive

92/675 19:6 June 1990

hemorrhagic infarct in the right tem- poral lobe.

No evidence of severe hypoxemia was found in repeated analys is of blood gases during status epilepticus; therefore, no endotracheal in tuba t ion or artifical respira t ion was needed. Also, no hemodynamic, cardiovascu- lar, or respiratory side effects were observed in e i ther of the pa t i en t s after chloral hydrate administrat ion.

D I S C U S S I O N Chloral hydrate is a widely used

hypnotic drug. Its role as an anticon- vulsant is not clear, and only a few reports have proved its efficacy.

Choral hydrate has been used to treat te tanus and eclampsia. Experi- menta l research has indicated a sup- pressive effect in a t tacks produced e x p e r i m e n t a l l y by s t r i chn ine , pen- t y l e n e t e t r a z o l , or e lec t r i c shock. 4 It also proved to be effective in cases of m y o c l o n i c epi lepsy, s Very few repo r t s d e s c r i b e i ts e f f e c t i v e n e s s in t r e a t i n g s t a t u s e p i l e p t i c u s in adultsl,2, 6 or children. 3

C h l o r a l h y d r a t e is the h y d r a t e form of chloral-(2,2,2,- t r ichlorace- talaldehyde) and is rapidly reduced by a l coho l d e h y d r o g e n a s e to tr i - chlorethanol, which is most probably the effective central nervous system depressant substrate. In contras t to chloral hydrate, t r ichlorethanol has a m u c h longer ha l f - t ime (four to 12 hours). The mechan i sm of chloral hy- drate as an ant iconvuls ive drug is un- clear. Studies have reported changes in the responsiveness of the central serotonergic neurons in feline dorsal raphae nucleus after t rea tment wi th chloral hydrate. 7

This report describes five adult pa- t ients in a state of status epilepticus who were treated wi th 30 mg/kg in- trarectal chloral hydrate. In all pa- tients, chloral hydrate was adminis- tered after ineffective t rea tment wi th c o n v e n t i o n a l d r u g s s u c h as di- azepam, d i p h e n y l h y d a n t o i n , phe- nobarbital, and sodium valporate as a last a t tempt before inducing barbitu- rate coma.

A combined admin i s t r a t ion of di- azepam and d iphenylhydanto in , 7 or phenobarbital s is the drug t rea tment of choice for status epilepticus. The c o m b i n a t i o n of d i a z e p a m and di- p h e n y l h y d a n t o i n has been effective in 88% of pa t ien ts wi th status epi- lepticus. 9

Some s tud ies describe successful

trials wi th sodium valporate, lO-12 lor- azepam, 13 clonazepam, 4 or midazo- lam. 14

Nevertheless , cer tain pat ients , es- pecially those wi th organic brain le- sions, r ema in uncont ro l lab le . Some authors recommend another trial of m o n o d r u g therapy - u sua l l y lido- c a i ne or p a r a l d e h y d e ( ace t a lhyde polymer) - for 20 minu tes after ther- apeutic failure. Is

We used chloral hydrate in patients wi th res i s tan t s tatus epi lept icus 50 to 60 m i n u t e s after failure of stan- dard therapy as the last step before barbi tura te coma. We chose chloral hyd ra t e because of i ts safe ty and lower r isk of side effects compared w i th paraldehyde. Chlora l hydra te and paraldehyde are closely related drugs tha t cause rapid seda t ion by s imilar mechan i sms . Whi le paralde- hyde may cause severe side effects such as h y p o t e n s i o n , p u l m o n a r y h e m o r r h a g e a n d e d e m a , v e n o u s thrombosis , kidney, and liver dam- age, 16 chloral hydrate is much safer; the most c o m m o n side effect of chlo- ral hydrate is gastrointest inal irrita- t ion due to oral administrat ion.

R e s u l t s f r o m t r e a t m e n t of the above-ment ioned patients, who were successfully treated wi th chloral hy- &ate, raise the possibility of its use as an al ternative drug in treating pa- t ients wi th intractable status epilep- ticus. It is worth not ing that no fail- ure of chloral hydrate t r ea tmen t or significant side effect could be dem- onstrated.

It is i m p o s s i b l e to d e t e r m i n e whether chloral hydrate acts alone or through potent ia t ion of the previous drugs given to pat ients wi th status epilepticus. This point may be eluci- dated by an ini t ia l trial of chloral hy- drate as a first-choice drug in treating patients wi th status epilepticus. The excellent effect of intrarectal admin- istrat ion of chloral hydrate in our se- ries suggests the advantage of using chloral hydrate when IV access can- not be obta ined and in pat ients in w h o m s t a n d a r d t he r a py drugs are medical ly contraindicated. However, because of the l imited number of pa- t ients in our series, a control study to evaluate the efficacy of chloral hy- drate as a supplement is needed be- fore it can be accepted as a rout ine therapy.

SUMMARY Five pat ients with intractable sta-

tus epilepticus, three of w h o m had organic les ions , were t rea ted suc- cessful ly w i t h chloral hydrate en- emas. Epileptic activity ceased clini- cally and electroencephalographical- ly w i t h i n a shor t period. No side effects were noted. The possibility of introducing this t rea tment for cases of epilepticus is raised considering its safety and efficacy.

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12. Snead OC, Miles MV: Treatment of status epilepticus in children with rectal sodium val- porate. J Pediatr 1985;106:323-325. 13. Tinuper P, Aguglia V, Gastaut H: Use of clobazepam in certain forms of status epilep- titus and in startle induced epileptic seizures. Epilepsy 1986;27:18-25. 14. Egli M, Albani C: Relief of status epilep- titus after intramuscular administration of mid- azolam, in Katsuki 8, Tsubaki T, Tokoyura Y teds): World Congress of Neurology. New York, Excerpta Medica, 1982, p 44. 15. Delgado-Escueta AV, Wasterlain C, Treiman DM, et al: Current concepts in neurology - Management of status epilepticus. N Engl J Med 1982;306:1137-1140. 16. Harvey SC: Hypnotics and sedatives, in Gilman AG, Goodman LS, Rall TW, et al leds): The Pharmacological Basis of Therapeutics, ed 7. New York, MacMillan, 1985, p 366-367.

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