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Incompatibility of Hexabrix and Papaverine

Thomas J. PiIIa,1 Shirley E. Beshany, and John B. Shields

Recently, new low-osmolality contrast agents have become Results

available for use in angiography. Several studies have shown
A mixture of Conray 60% with i ml of Papaverine HCL
decreased cardiac effects, renal toxicity, pain, and possible
failed to produce any kind of precipitation. Renografin-76 with
allergic reactions with the use of these agents [i -4]. How-
i ml of Papaverine caused a “white suspension” that disap-
ever, no information is available concerning the compatibility
peared after i -2 mm. There was no precipitation. Amipaque
of these new drugs with the various pharmacologic agents
(220 mgI/cc) and i ml of Papaverine resulted in no precipita-
used in visceral angiography. We recently observed that
tion. One ml of Papaverine mixed with Hexabrix demonstrated
loxaglate meglumine (Hexabrix) and Papaverine Hydrochlo-
precipitation of a white amorphous material which, left undis-
ride (HCL) precipitated upon contact. This led to further
turbed, persisted for 24 hr. When the precipitate was shaken
investigation of the compatibility of these two agents.
vigorously, it dissolved completely within 20-30 mm. The
results of mixing Papaverine in various dilutions with Hexabrix
Materials and Methods are shown in Table i.

Undiluted Papaverine HCL (Lilly, Indianapolis, IN), Conray 60%

(iothalamate meglumine USP 60%, Mallinckrodt, St. Louis, MO),
Aenografin-76 (diatriazoate meglumine, Squibb, New Brunswick, NJ), Discussion
Amipaque (metrizamide 48.25% iodine, Winthrop, New York, NY)
Pharmacologic agents are widely used in both peripheral
and Hexabrix (ioxaglate meglumine 39.3% and ioxaglate sodium
i 9.6%, Mallinckrodt) were used. The Hexabrix that was used had and visceral angiography. Papaverine is used to assess the
expiration dates of 9/87 and 2/86 and was from Lots Xi 49E and significance of a stenosis in the vascular bed, improve visual-
V023C, respectively. Undiluted Papaverine HCL was mixed with 3 ml ization of the arterial system and portal venous system, and
of each of the above-named contrast agents and the solution was decrease arterial spasm [5-7]. The dose of Papaverine ad-
observed for precipitation. In addition, Papaverine HCL was diluted ministered varies from 30-60 mg (1 -2 ml of undiluted Papav-
in various amounts of normal saline and mixed with Hexabrix. This erine). The method of administration varies from direct infu-
was also evaluated for precipitation (Table i). Each experiment was sion to the use of saline dilutions in various concentrations
performed three to five times. [6, 7]. Reported side effects include a temporary drop in blood
pressure and, if a complete heart block is present, ventricular
TABLE 1 : In Vitro Evaluation of Papaverine Hydrochloride and arrhythmias [6, 8]. Little information is available on the bio-
Hexabrix compatibility of Papaverine with contrast agents, including
the new low-osmolality agents. Our study suggests that
Sam#{216}e
PreaPitate Papaverine should be used with extreme caution during an-
Papavetine Saiine Hexabtix
(ml) (m (ml) giography when Hexabrix is the contrast agent used. Undi-
1 0 5 Yes luted Papaverine, when mixed with Hexabrix, was found to
i i 5 Yes precipitate immediately. When the Papaverine was diluted,
i 2.5 5 Yes the chance of precipitation decreased. When 30 mg (i ml) of
i 5 5 Yes Papaverine was diluted in 20 ml of normal saline, no precipi-
1 i0 5 Suspension that clears tate was observed. However, 60 mg (2 ml) of Papaverine
i 15 5 Suspension that clears
i 20 5 No diluted in 20 ml of normal saline resulted in precipitation.
1 iO 15 No When Papaverine was tested with Renografin, Conray, Ami-
1 10 30 No paque, and Metrizamide, no precipitate was observed. The
2 10 5 Yes exact chemical reason for precipitation of Hexabrix with Pa-
2 15 5 Yes
paverine is not clear. Whether it is due to a pH difference or
2 20 5 Suspension that precipitates
a precipitation of salts is speculation. The precipitate is dense

Received December 17, 1985; accepted after revision February 15, 1986.

I Department of Radiology, St. Louis University Medical Center, 1325 S. Grand Blvd., St. Louis, MO 631 04. Address reprint requests to T. J. Pilla.

AJR 146:1300-1301, June 1986 036i-803X/86/i466-i300 0 American Roentgen Ray Society

AJR:i46, June 1986 INCOMPATIBILITY OF HEXABRIX AND PAPAVERINE 1301

and can last for 24 hr. Thus, meticulous angiographic tech- Invest Radiol i982 (May-June);i7:284-29i
nique should be used when Papaverine and Hexabrix are 2. Nilsson PE, Holtas SL, Tyler LT. Subjective responses and
used during the same angiographic study. Hexabrix and albumin induced by loxaglate during renal angiography in man.
Radiology i982;i 44:509-Si 2
Papaverine should never be mixed together. Thorough flush-
3. Sacks BA, Ellison HP, Bartek S. A comparison of Hexabrix and
ing of the catheter with normal saline before the injection of
Aenografin 50 in peripheral arteriography. Invest Radio! i984;
Papaverine is necessary when Hexabrix is being used as the
Suppl i 9:5320-5322
contrast agent. In addition, 25 ml of normal saline should be 4. Dawson P. New contrast agents-chemistry and pharmacology.
used to dilute each milliliter of Papavenne before injection. Invest Radio! 1984; Suppl i9:S293-S300
The chemical compatibility of Hexabrix with other pharmaco- 5. Kaufman SL, Fara JW, Udoff EJ, et al. Hemodynamic effects of
logic agents used in angiography remains to be studied. Until vaso dilators
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7. Gerlock AJ Jr, Mirfakhraee M. Essentials of diagnostic and
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