A simle, effective method of treating vertigo patiets

A SIMPLE, EFFECTIVE METHOD OF TREATING VERTIGO PATIENTS

Brajendra BASER, M.S. and Santosh K. KACKER, M.S., FRCS

Department of Otolaryngology, All India Institute of Medical Science, New Delhi, India

Medical treatment of vertigo even today is far from satisfactory. A controlled clinical trial of treating vertigo patients by 1% ephedrine hydrochloride nasal douche has been conducted in 84 patients; 74.3% patients were either completely or partially relieved of their dizziness. The therapy was well accepted by patients and side effects were minimal.

The concept of intranasal route of drug administration is not new. In Ayurvedic medicine, "Narya Karma" (nasal therapy) is a recognized form of therapy; since ancient times psychotropic drugs and hallucinogens have been used as snuffs by the South American Indians.  In recent times, powdered snuff of the posterior pituitary has been used for inducing labor; also, intranasal spray of antidiuretic hormone is used to control diabetes insipidus. Interest in the intranasal route of drug administration has been revived by Anand Kumar and associates (ANAND KUMAR, DAVID, UMBERKAMAN, and SAINI, 1974; ANAND KUMAR, DAVID, and PURI, 1977; ANAND KUMAR, DAVID, KUMAR, UMBERKOMAN, and KRISHNAMOORTHY, 1978; ANAND KUMAR, SEHGAL, DAVID, BAJAJ, and PRASAD, 1980). The pharmacological effect of administering steroids intranasally has been initially tested in fertility regulation. These studies have shown that ol­ factory epithelium constitutes a portal for substances to enter the central nervous system and thus offers a potential and convenient site for delivery of drugs with the advantage of reduction in dosage and side effects (GoPINATH, GoPINATH, and ANAND KUMAR, 1978).

Ephedrine hydrochloride given as a nasal douche for treatment of vertigo has been tried successfully by previous workers (SHAH and SHAH, 1981).

The present study is designed to examine efficacy of 1 % ephedrine hydrochlo­ride nasal douche in treatment of vertigo. The study was carried out between the period of November 1982 to June 1984 at the All-India Institute of Medical Sci­ ences, New Delhi, India.

Received for publication  November 6, 1989

Paper presented at the XII NES International Meeting, New Orleans, U.S.A.

165

STUDY DESIGN

It was a single-blind placebo controlled study and was conducted in accord­ ance with the Helsinki declaration on human investigation. Case selection in this study was random, without any bias of age, sex, etiological diagnosis or dura­tion of vertigo. Cases were divided in to two groups-the smaller Group A (control group) and the larger Group B (main group). Group A cases received placebo nasal douche on alternate days for five times and Group B cases received I % ephedrine hydrochloride nasal douche on alternate days for five times. All patients were informed about the procedure prior to entry into the study. In­ completely investigated cases or cases with follow-up of less than 3 months were dropped from this study.

Response to treatment was determined as follows:

• Response a-Patient free from dizziness for 3 months or
• Response b-Partial relief of dizziness (50 % or more).
• Response c-No relief of

Patient population.   Eighty-four patients complaining of objective/subjective rotatory vertigo served as subjects for this clinical trial; age range was from IO years to 99 years (Table I); duration of vertigo ranged from 10 days to 10 years. The majority of the patients had a history of dizziness for less than one year. Method of giving 1% ephedrine hydrochloride nasal douche. Pulse and blood pressure were recorded before starting the procedure.  The patient was asked to

sit on a chair with head bent forward and downward; then 2 oz of 1 % ephedrine

hydrochloride solution was pushed with pressure into one of the nostrils by a Higginson's syringe. The patient was asked to hold his breath to prevent entry of the solution into the oropharynx. The procedure was repeated in the opposite nostril. Blood pressure and pulse were recorded again.

Estimation of serum ephedrine level was done in samples taken 5 and 15 min after giving the nasal douche; this was done in IO cases only.

Observations. Prior to entry into the study, all patients received a thorough clinical examination including detailed disease history and laboratory tests. All patients underwent a battery of audiological and vestibulometric tests. Electric

Age

Table 1.  Age and sex distribution.

Group A (n=l4)                                          Group B (n=70)

Table 2.  Pattern of hearing loss in Groups A and B.

No. of patients (%)

Type of hearing loss

Table 3.  Abnormal vestibulometric findings in Groups A and B.

Type III Type IV

Optokinetic nystagmus Bithermal caloric

Canal paresis Hyperactive response

21.4

14.3

32.9

10.0

Table 4. Etiological diagnosis of vertigo in Groups A and B.

response audiometry and computerized tomography was done in selected cases. Summary of audiological and vestibulometric tests is given in Tables 2 and 3. Etiological diagnosis.  Out of the known-diagnosis category, central vascular cause was the commonest followed by sinugenic vertigo (Table 4). Spectropho­ tometric analysis of blood samples did not reveal systemic absorption of ephedrine

in any of the cases.

RESULTS

In Group B, treated by 1 % ephedrine hydrochloride nasal douche, 74.2 %

Table 5. Results of 1% ephedrine hydrochloride nasal douche according to etiological diagnosis (Group B).

Etiological diagnosis

Total No.                            Response to therapy

Table 6. Comparison of results in Groups A and B. Group A: treatment by placebo nasal douche; Group B: treatment by 1 % ephedrine hydrochloride nasal douche.

Response (%)

Group

a                                        b                                       C

A                                      0.0                                  14.2                                  85.7

B                                     55.7                                  18.5                                  25.7

Chi-square value 19.68; p<0.001.

of the patients had partial or complete improvement in their symptoms (responses a and b), while only 14.2% of the cases in Group A showed partial response to placebo therapy. On statistical analysis, these results are significant (Chi-square value 19.68; p<0.001). Details of results are given in Tables 5 and 6.

Side effects

Side effects of this therapy were minimal. None of the cases reguired dis­ continuation of therapy because of side effects. The most common side effect was heaviness of head (36.7 %), which subsided in most of the cases after 2 or 3 douches. Other side effects noted were euphoria (1.4 %), burning sensation in the hands and feet (2.8 %), increased frequency of micturition (2.8 %), palpitation (1.4 %), and insomnia (2.8 %).

DISCUSSION

Unfortunately, the therapeutic part is still evolving. After a long, tedious otoneurological examination, even today we find there are many of these patients and have little more to offer apart from rest sedation and exercises. This clearly suggests a need for new methods of treating vertigo patients.

The idea of using ephedrine saline nasal douche for treatment of vertigo originated by chance. A patient with sinus headache who was being treated by ephedrine nasal douche reported relief from both his vertigo and headache (SHAH, KERAWALA, and KOTHARI, 1973).

Subsequently, ephedrine nasal douche was tried in vertigo patients and found to be effective in a large number of cases (SHAH and SHAH, 1981).

Ephedrine is an alkaloid obtained from plants of the genus Ephedra and preparations of these were used in China at least 5,000 years ago under the name "Ma Hung," meaning yellow house. Ephedrine was introduced in Western medicine in 1923 and was the first sympathomimetic drug to be used.

The exact mechanism of action of the ephedrine hydrochloride nasal douche is not known. However, the following mechanisms are suggested:

• Middle ear pressure-change. It has been known to many otologists that inflation of the middle ear could help many patients with vertigo (BooTH, 1979). Middle ear pressure-change secondary to wax or foreign body pressing over the tympanic membrane is known to produce vertigo. Eustachian tube blockage has been mentioned as a common cause of vertigo in a standard text­ book of neurology (WALTON, 1977). Very small differences that are difficult to measure by acoustic impedance or audiometry may produce changes in sub­ jective Even insertion of a grommet tube has been recommended (BOOTH, 1979). HALL and BRACKMAN (1977) showed intermittent mild eustachian tube blockage in nearly one-third of their cases of Meniere's disease; they noted the negative pressure was great when symptoms were maximum. In alternobaric vertigo, ambient pressure changes are said to produce a transient disturbance of vestibular function (LUNDORGREN, 1965); the vertigo troubles aircrews much more when there is associated eustachian tube dysfunction secondary to the common cold or other upper respiratory tract infection.

The vasoconstrictive decongestive action of ephedrine hydrochloride solution may be effective in relieving vertigo by opening up of the eustachian tube.

In our study, 30 % of the cases had a history of recurrent upper respiratory

tract infection and demonstrable focus of infection in the upper respiratory tract. It is likely many of them may have vertigo due to associated eustachian tube dysfunction. Improvement in middle ear pressure due to the vasoconstrictive, decongestant action of ephedrine on eustachian tube opening may be one of the mechanisms of action.

• Paranasal sinus infection and vertigo. Association of paranasal sinus infection and vertigo has been claimed by many authors. HAID (1981) described the so-called sinugenic vertigo. He suggests that an interrelationship exists between pathological trigeminus reflex via the sphenopalatine ganglion triggered off by maxillary sinusitis and a reflectory labyrinthine irritation results in vertigo. COATS (1969) suggests a new clinical entity-isolated vestibular deficit associated with sinusitis.

Ephedrine hydrochloride nasal douche has been used as a therapy for max­ illary and frontal sinusitis; the vasoconstrictive decongestant action of ephedrine may be improving drainage from paranasal sinuses and hence the relief in vertigo may be by virtue of the therapy of sinusitis.

However, both the above explanations are not true in the cases of vertigo who do not have any history of upper respiratory tract infection or do not have any evidence of sinus infection.

• Central actions of Ephedrine in therapeutic doses is known to have a stimulatory action on the central nervous system. Probably by its action on the reticular activating system, ephedrine and the related compound D-ampheta­ mine affect the vestibular system and have been used successfully in management of motion sickness. A mixture of amphetamine and atropine is recommended as the most effective treatment against motion and space sickness (GRAYBIEL, MILLER, and HoMICK, 1974). Drugs like caffeine and amphetamine intervene in the transmitter mechanism of the subrostral system, which exerts a subduing effect upon the mesencephalic nystagmus generator. Ephedrine resembles D-amphetamine both in chemical structure and pharmacological actions. In this study, it was seen that ephedrine hydrochloride given as a nasal douche is not absorbed systemically, as none of the cases demonstrate significant change in blood pressure and heart rate, which are usually seen with oral ephedrine; also,

ephedrine could not be detected by spectrophotometric analysis of blood samples of 10 patients, taken at 5 and 15 min after giving l % ephedrine hydrochloride nasal douche. However, CNS side effects were seen in 3 patients (4.3 %), who complain­ ed of euphoria and insomnia. Possibly ephedrine hydrochloride given as a nasal douche is absorbed directly from nasal mucosa into cerebrospinal fluid and affects the vestibular nuclei directly or by virtue of its action on the reticular activating system. The concept of a connection between cerebrospinal fluid and nasal mucosa is not new (FIELD and BRIELY, 1948). Recently, ANAND KUMAR et al. (1980) performed several experiments on rhesus monkeys and demonstrated that drugs can be absorbed directly from nasal mucosa to cerebrospinal fluid without systemic absortion and thus much higher concentration can be achieved at the

target site in the brain; also, the drug doses and systemic side effects can be re­ duced. GoPINATH et al. (1978) studied the transfer pathway of intranasally sprayed colloidal gold particles by electron microscopy and demonstrated that substances sprayed intranasally on the olfactory mucosa take two different routes, one through the neuronal tissues and the other through the supporting cells.

From this study it is evident that 1% ephedrine hydrochloride nasal douche

is effective in therapy of vertigo in widely different etiological groups. It is possible that the treatment might have more than one mechanism of action. However, the above last-mentioned mechanism action suggested, explains the efficacy of the 1% ephedrine hydrochloride nasal douche in most cases.

Though the exact mechanism of action of this treatment is uncertain, the

therapy is simple, effective, and inexpensive and free of any significant side effects and certainly deserves to be given a trial.

REFERENCES

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activity by body fluids and tissues in rhesus monkeys after intravenous injection or in­ tranasal spray of tritium labelled estradiol and progesterone. Curr. Sci. 43: 435-439, 1974. ANAND KUMAR, T. C., DAVID, G. F. X., and PURI, V.: Ovulation in rhesus monkeys suppressed by intranasal administration of progesterone and norethisterone. Nature 270: 532-533,

1977.

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COATS, A. C.: Directional nystagmus and spontaneous nystagmus as observed in electronys­ tagmographic examination. Ann. Oto!. Rhino/. Laryngol. 75: 1155, 1969.

FIELD, B. J., and BRIELY, J.B.: Lymphatic connections of the subarachinoid space. Br. Med.

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GOPINATH, P.G., GoPINATH, G., and ANAND KUMAR, T. C.: Targetsiteofintranasallysprayed substances and their transport across the nasal mucosa: A new insight into intranasal route of drug delivery. Curr. Ther. Res. 23: 597-606, 1978.

GRAYBIEL, A., MILLER, E. F., and HoMICK, J. L.:      Experiment M-131 human vestibular function.

1. Susceptibility to motion sickness. In Proceedings of Skylab Science Symposium Report TMX-58154 Houston, Texas NASA I, 169, 1974.

HAID, T.:     Vertigo originating from inflammation of paranasal sinuses (the so-called sinugenic vertigo) Adv. Otorhinolaryngol. 27: 190-197, 1981.

HALL, C. M., and BRACKMAN, D. E.:      Eustachian tube blockade and memory disease.  Arch.

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LUNDORGREN, C. E.G.: Alternobaric vertigo-A diving hazard.  Br. Med. J. 11, 511-514, 1965.

SHAH, K., KERAWALA, S. P., and KOTHARI, A.:       Ephedrine nasal irrigation in treatment of sinus

headache. Paper read at the Xth International Conference of Otolaryngology Venice, 1973. SHAH, K. U., and SHAH, A.:       Labyrinthine vertigo treatment with ephedrine nasal douche.  J.

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WALTON, J. (ed.): Vertigo, Brain's Diseases of the Nervous System (8th ed.), pp. 197-202, Oxford University Press, Oxford, 1977.

Request reprints to: Dr. B. Baser, Lecturer, Department of Otolaryngology Head and Neck Surgery, T. N. Medical College and BYL Nair Charitable Hospital, Dr. A. L. Nair Road, Bombay 400 008, India