Dimethyl sulfoxide lowers icp after closed head trauma brain anoxia

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Dimethyl

Sulfoxide lowers ICP after closed head trauma

M. Karaca, U.Y. Bilgin, and M. Akar

Division of neurological surgery, university ot dicle,

Turkey

J.C. De la torre division of neurological surgery, university of ottawa,

Canada

Received. June 16, 1990

Abstract

Ten patients with closed head trauma and elevated intracranial

Pressure (ICP) ranging from 40-127 mm hg. Were treated

With intravenous dimethyl sulfoxide (DMSO) every 6 h

For 1-10 days. Four patients received DMSO and intermittent

Oxygen. All patients showed a reduction of ICP after

24 h and 7 had normal ICP after 6 days of treatment.


Two patients died of their injuries.Neurological assessment

At the time of discharge showed 2 patients with severe

brain anoxia

Neurological deficits and 6 patiencts with mild

To no deficit. After a 3 month followup, 1

Patient remained severely impaired and 7 patients showed

Mild to no deficit.It appears that intravenous DMSO

Can rapidly reduce elevated ICP in severe closed-head

Injury and that it improves neurological outcome.

Intravenous

Administration

Intravenous administration of dimethyl sulfoxide (DMSO)

Has been shown to be clinically useful in lowering intractably

Raised intracranial pressure 1, 2 and

Increasing cerebral blood flow in brain-damaged pauents, 3

Or after experimental brain injury. 4, 5 DMSO has a number of biological

Actions that may be useful in the clinical treatment

Of CNS trauma; for example, it can function in experiments

brain anoxia

As a free radical scavenger, powerful diuretic, calcium

Ion flux antagonist, platelet deaggregator and cell

Membrane stabilizer. 6 in addition,

DMSO can reduce brain oedema 7 and increase

Cerebral perfusion pressure 8 following

Experimental trauma.

Subjects

And methods

10 head injury patients were studied. Their glasgow

Coma scale score at time of admission ranged from 3-9

(average 6) and rose to 15 in 8 of the 10 patients following

Treatment ( fig.1). All patients

Had severe closed-head trauma and had an ICP monitor

Installed epidurally through a burr hole shortly after

Admission. The mean ICP on admission was 73 mm hg (range

40-127 mm hg; normal 5-13 mm hg). CT scans were made

Before and after treatment and at the time of discharge.Brain anoxia

DMSO (rlmso-100): research industries. Salt lake city,

UT) was administered every 6 h. The 28% solution was

Diluted with physiological saline (56: 200 ml) to give

A final dose of 1.12 g kg-¹ delivered intravenously

At a fast drip rate. Blood pressure was not affected

In patients receiving DMSO. All patients were ventilated

And in four of them oxygen 2 1 min was administered

Intermittently for the first 24 h after admission. The

Dose of DMSO was reduced by half when the ICP reached

20 mm hg or lower and was continued until ICP stabilized

Or full recovery was observed.

Results

The effect of DMSO ( n = 6) or DMSO + oxygen

( n = 4) on intracranial pressure in 10 head injury

Patients is shown in fig. 1 at

24 h and 6 days after treatment.Brain anoxia all patients responded

To treatment, with a mean reduction in ICP at

24 h of 28 mm hg (DMSO alone) and 39 mm hg (DMSO + oxygen).

After 6 days. The mean ICP reduction was 58 mm

Hg (DMSO alone) and 49 mm hg (DMSO + oxygen) compared

To pretreatment values.Although lowering ICP was dramatic,

Being seen in most cases within the first 30 min of

DMSO administration, the effect was not sustained and

Most patients required maintenance doses for 2-10 days

To minimize fluctuation in ICP. Increasing the dose

Of DMSO above that used initially was not associated

With a greater reduction in ICP. Unlike mannitol, which

Was used in another group of patients, sudden rebound

Phenomena were not seen in patients treated with DMSO.Brain anoxia

In a further group, dexamethasone was ineffective in

Lowering ICP. All patients received 15% dextrose in

Water 1 l/d as fluid replacement. Mean urine output

Was 1430 ml per day and averaged a brisk 238 ml 2 h-¹

Period during DMSO treatment. The haematocrit and haemoglobin

Levels remained normal. Renal function tests and serum

Electrolytes were normal during treatment and at discharge

In all patients. CT scans confirmed

The reduction in brain swelling following DMSO administration.Neurological

Assessment of the treated patients 6 days after DMSO

Administration was as follows: 2 patients showed severe

CNS deficits (hemiparesis and cognitive impairment),

2 patients had moderate CNS impairment and 6

Patients had mild or no deficit.Brain anoxia two patients

Eventually died. In a follow-up 3 months after discharge,

1 patient showed no improvement from severe deficits

And the remaining 7 patients showed mild to no

Deficit.

Figure

1

Fig. 1. Comparison of intracranial

Pressure (ICP) in 10 patients following closed head

Injury pre-treatment, 24 h after treatment with DMSO

And 6 days after treatment. Numbers in parenthesis

Are glascow coma scale at admission ( left of fig.)

And 6 days after treatment ( right of fig.)

Conclusions

This pilot study indicates that DMSO is effective reducing

Intracranial pressure in patients with a closed head

Injury and may improve outcome. Unlike two previous

Reports showing a reduction by DMSO of intracranial

Hypertension but no effect on mortality, 1,

brain anoxia

2 the present study shows improvement both in neurological

Outcome and survival in 7 patients followed for 3 months

After their injury. Little or no rebound of ICP was

Observed after DMSO. The drug appeared more effective

When oxygen was delivered during the recovery period

( fig. 1), but this effect may

Have been due to the initially lower ICP on admission

Shown by the 4 patients in that group. DMSO may facilitate

Transport of oxygen molecules to ischaemic/hypoxic CNS

Tissue and may limit the formation of superoxide radicals

From the available oxygen. 9, 10. The

Present study supports previous observations on the

Value of DMSO in patients with severe head trauma and

Intractable ICP who were refractory to conventional

brain anoxia

Therapy. 1, 2it is concluded that DMSO

Can effectively lower ICP in patients with closed-head

Injury and may have a positive effect on neurological

Outcome. There were no serious side effects after DMSO

Administration and the drug appeared safe in moderately

High doses over 10 days. A more extensive clinical trial

Of DMSO in head injury patients is warranted.

References

• walter F, tanabe C, paxton H (1983)

Treatment of elevated incranial pressure with dimethyl

Sulfoxide. Ann NY acad sci 411: 286-292.

• marshall LF, camp P, bowers S (1984)

Dimethyl sulfoxide for the treatment of intracranial

Hypertension. A preliminany trial. J neurosurg

14: 659-663.

• mullan S, jafar l, hanlon K, brown

F (1980) dimethyl sulfoxide in the management of postoperative

brain anoxia

Hemiplegia. In: wilkins RH (ed) cerebral arterial

Spasm. William and wilkins. Baltimore, pp 646-653.

• de la torre JC, rowed D, kawanaga

H, mullan S (1973) dimethyl sulfoxide in the treatment

Ot experimental brain compression. J neurosurp

38: 345-354.

• james HE, camp P, harbaugh R, marshall

L (1983) comparison of the effects of DMSO and pentobarbitone

On experimental brain oedema. Acta neurochir 60:

245-255.

• de la torre JC (1983. Ed) biological

Actions and medical applications of dimethyl sulfoxide.

Ann NY acad sci 411: 1-403.

• brown FD, johns L, mullan S (1983)

Dimethyl sulfoxide therapy following penetrating brain

Injury. Ann NY acad sci 411: 245-252.

• james RE, camp P, harbaugh R, marshall

L, werner R (1982) companson of the effects of DMSO

brain anoxia

And pentobarbitone on experimental brain oedema.

Acta neurochir 60: 245-255

• de la torre JC (1983) role of dimethyl

Sulfoxide in prostaglandin-thromboxane and platelet

Systems after cerebral ischemia. Ann NY acad sci

411: 293-308.

• park DA (1983) role of oxygen-derived

Free radicals in digestive tract diseases. Surgery

94: 415-422.

Author

Information J.C. De la torre, MD. PhD

Division of neurosurgery

University of ottawa health sciences

451 smyth road

Ottawa. Ontario KIH 8M5

Canada

Source

Eur J clin pharmacol (1991) 40:113-114003169709100019B

DMSO organization wishes to thank the publisher of

The european journal of clinical pharmacology

Who has granted us permission to place this article

On the world wide web for world-wide distribution.Brain anoxia the

Publisher retains all copyright. Permission to copy

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Must be obtained from the publisher.