BRIEF REPORT

DRUG EFFICACY AND SIDE EFFECTS FOLLOWING DIFFERENT FORMULATIONS OF INTRAVENOUS DIAZEPAM;

M a,ry Craig and J. F. Fielding *

Department of Medicine and Gastroenterology, The Charitable Infirmary, Jervis Street, Dubfin 1.

Summary Intravenously injected diazepam in emulsion

form (Diazemuls) was associated with signific- antly fewer painful injections and significantly less indirectly assessed phlebitis compared with the same drug with propylene glycol as a solvent (Valium). No, differences in drug efficacy was noted between the 2 preparations.

Introduction Intravenous dlazepam injection has been asso-

ciated' with pain on injection and thrombophletltis (Langdon et at, 1973). Diazepam is lipid soluble and therefore difficult to dissolve in water. To overcome this difficulty commonly used injectable forms of diazepam contain solvents such as propylene glycol or phenylcarbinol with ethanol. It is felt that the side effects of intravenous diaze- pam are due, at least in part, to these solvents. Recently diazepam has been dissolved in soya- bean oil and then emulsified in water.

This paper reports a comparison between diazepam in emulsion form and diazepam with an organic solvent. It compares their sedative efficacy in relation to upper intestinal endoscopy, the incidence of pain associated with their in- jection and, indirectly the frequency of phlebitis associated w~th each preparation.

Patients and~ Methods On a prospective basis 100 consecutive patients

undergoing upper intestinal endoscopy entered the study. On a stratified randomised order each patient was given 20 mg of diazepam either in emulsion form (Diazemuls) or with pro,pylene glycol as solvent (Valium). All injections were given by one of the authors who recorded any adverse comments made by the patient during the injection. Efficacy of sedation was assessed in the short term by the acceptability of the endoscopic procedure to the patient. Twenty-four hours later the second author, not knowing which preparation, had been given, asked the patient if they had any complaints concerning the injection.

* Requests for reprints to Dr. J. F. Fielding at the above address.

They were also asked if they liked, disliked, or neither liked nor disliked' the endoscopic, pro- cedure. Retrograde amnesia for the procedure was taken as evidence of drug efficacy. The second author also examined' the site of the injection and recorded the s~te as normal, locally

TABLE Diazepam efficacy and side effects.

Diazepam preparation given

Emulsion Propylene Parameter form glycol solvent

Number studied 50 50

Males/Females 24/26 24/26

Age range (mean) 15-79 19-74 in years (40.0) (40.4)

Immediate patient complaint 1 0

Adequate sedation 49 50

Patient complaint at 24 hours 2 9*

Patient reaction to endoscopy

Liked 1 0 Disliked 2 2 Neither 13 15 Didn't remember 34 33

Inspection of injection site at 24 hodurs

Normal 22 17 Locally reddened 22 26 Diffusely reddened 6 7

Palpatation of injection at 24 hours

Non tender 45 37 Tender 5 13"

* P < 0.05

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80 IRISH JOURNAL OF MEDICAL SCIENCE

reddened if there was reddening at the site of the injection only, or diffusely reddened ff red- denmg extended along the line of the injected vein. The s~te of injection was palpated and recorded as non tender or tender.

Difference in results were tested for significance by X '~ analyses with the correction factor of Yates included. From the X 2 values obtained the appro- priate 'P' values were derived.

Resu,lts

The results obtained are shown in the Table. The one immediate complaint was pain at the site of injection. This patient repeated this com- plaint at 24 hours and one other patient who recewed the emulsion form complained of pain in the region of the left shoulder during injection in the left antecubital fossa. Of the 9 complaints following infusion of diazepam with pro pylene glycol as solvent 6 were of pare at the site of injection and 3 of pain up the left arm during iniection in the left antecubital fossa.

Discussion

The 2 groups are obviously comparable. Whilst ~t is difficult to evaluate, the clinical response to, diazepam injections (Van Dardel eta/, 1976) the drug in emulsion form was deemed to produce adequate sedation Jn 49 of the 50 patients by an experienced endoscopist. Moreover the incidence of retrograde amnesia was essentially the same

following both preparations indicative of no loss of drug effect when given in emulsion form. This is in keeping with the findings of Thorn-Alquist (1977).

The incidence of painful injections snd phlebitis (as indirectly assessed in this study) were both significantly less in those who received diazepam in emulsion fo, rm. Similar findings have been reported' by Olesen and~ Huttle (1980).

This study suggests that intravenous d~azepam in emulsion form is associated with fewer side effects than when given with propylene glycol as a solvent, w~thout loss of drug efficacy.

Diazemuls was kindly supplied by Kabivitrum.

References

Ann-Marie Thorn-Alquist. 19.77. Parentera] use of diazepam in an emulsion formulation. A clinical study. Acta Anaesth. Scand. 21, 400-404.

Langdon, D. E., Harlan, J. R. and Bailey, R. L. 1973. Thrombophlebit is with diazepam used intravenously. J.A.M.A. 223, 184-185.

Olesen, A. S. and Huttel, M. S. 1980. Local reac- tions to I.V. diazepam in three, different formu- lations. Br. J. Anaesth. 52, 669-611.

Von Dardel, O., Me,bius, C. and Mossberg, T. 1976. Diazepam in emulsion form for intraven- ous usage. Acta Anaesth. Scand. 20, 221-224.