Indigo carmine only recently was found to have a vasopressor effect. Intravenous injection in anesthetized and unanesthetized patients resulted in blood pressure elevation and bradycardia. This effect appears analogous to that of serotonin which indigo carmine structurally resembles. This drug should be used with caution in patients with cardiovascular disease

Johnson, Arthur J.

Wu, C. C.

English

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Henry Ford Hospital Medical JournalVolume 17 | Number 2 Article 106-1969The Vasopressor Effect of Indigo CarmineC. C. WuArthur J. JohnsonFollow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournalPart of the Life Sciences Commons, Medical Specialties Commons, and the Public HealthCommonsThis Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in HenryFord Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons.Recommended CitationWu, C. C. and Johnson, Arthur J. (1969) "The Vasopressor Effect of Indigo Carmine," Henry Ford Hospital Medical Journal : Vol. 17 :No. 2 , 131-134.Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol17/iss2/10Henry Ford Hosp. Med. Journal Vol. 17, No. 2, 1969 The Vasopressor Effect of Indigo Carmine t C. C. Wu, M.D.* and Arthur J. Johnson, M.D.* Indigo carmine only recently was found to have a vasopressor effect. Intraven-ous injection in anesthetized and unanesthetized patients resulted in blood pressure elevation and bradycardia. This effect appears analogous to that of serotonin which indigo carmine structurally resembles. This drug should be used with caution in patients with cardiovascular disease. Indigo carmine, a dyestuff, was in-troduced into the medical field in 1903 by Voelcher and Joseph. Because it is concentrated in the kidney and excreted in the urine, it has been used as a test of renal function,* and in urologic procedures where its blue color aids in the identification of ureteral orifices during cystoscopy and open surgical operations.--' It has also been used in dye dilution methods for determining blood flow." Side effects of this dye were not reported untfl recently. We noted a vasopressor effect associated with its use and Erickson and Widmer,' and Kennedy et aF recently reported the same observation. This study was un-dertaken to document and to determine the nature of the vasopressor effect. Materials and Methods A total of 40 patients confined at * Division of Urology t Indigo Carmine, Hynson, Westcoff and Dunning, Baltimore, Md. Henry Ford Hospital with various urological illnesses were selected for this study. Their ages ranged from 23 to 75 years. Azotemic patients were excluded. They were divided into two groups. In group I , 20 patients received 5 ml of 0.8% indigo carmine intra-venously while undergoing endocysto-scopy or transurethral prostadc re-secdon during general or spinal anes-thesia. The base line blood pressure and pulse rate were recorded, and the dye was injected into the infusion tub-ing over a 30-second period. Blood pressure and pulse rate were recorded every minute until they returned to preinjection levels. In Group I I , the control group, sim-ilar data were collected from 20 pa-tients without sedation or anesthesia. All procedures were the same except that the dye was injected directly into the vein with a syringe. Results The base line systolic pressures 131 Wu and Johnson varied from 90 to 180 mm Hg and the diastolic pressures ranged from 60 to 110 mm Hg. Increased systolic and/or diastolic blood pressure and brady-cardia were observed in all cases within two minutes of completion of the in-jection. The maximal increase appeared in one minute in half of the cases, and in two to five minutes in the remainder. In Group I , systolic pressure in-creased 10-60 mm Hg and diastolic pressure increased 0-30 mm Hg. The average increases were 25 mm Hg systolic and 14 mm Hg diastolic, and the mean values were 20 mm Hg and 10 mm Hg respectively. In one patient the diastolic pressure did not change but systolic pressure increased by 20 mm Hg. Blood pressure returned to preinjection levels in 5 to 35 minutes, with a mean duration of 22 minutes. Pulse rate increased 4-20 beats per minute. (Table I ) In Group I I , systolic pressure in-creased 0-40 mm Hg and diastolic 0-32 mm Hg. Average increases were 15 and 13 mm Hg respectively while mean increases were 10 and 10 mm Hg. In one patient there was no change in systolic pressure but diastolic pressure increased by 6 mm Hg. In another patient, no change in diastolic pressure was observed, while systolic pressure increased by 10 mm Hg. Blood pres-Table I m m H g a PR/mm 160 140 120 100 8 0 H 6 0 0 • • MEAN SYSTOLIC PRESSURE Z^s A MEAN DIASTOLIC PRESSURE • • MEAN PULSE RATE iO 2 0 25 3 0 MIN CHANGES in BLOOD PRESSURE and PULSE RATE AMONG A N E S T H E T I Z E D CASES. 132 m m H g a PR/min. 160 140 -120 -100 -8 0 -60 The Vasopressor Effect of Indigo Carmine Table I I MEAN SYSTOLIC PRESSURE h A MEAN DIASTOLIC PRESSURE • • MEAN PULSE RATE 10 15 20 MIN. CHANGES in BLOOD PRESSURE and PULSE RATE AMONG UNANESTHETIZED CASES. sures returned to base line levels within 5 to 20 minutes while mean duration was 10 minutes. Pulse rate decreased by 2 to 20 beats per minute. (Table I I ) There was no relationship between the level of resting blood pressure and the amount of increase in blood pres-sure. No fll effects or allergic reactions were observed in any case. Discussion Indigo carmine, sodium indigotin disulfonate, is the aqueous solution of the sodium salt of indigotin disulfonic acid. It has a molecular weight of 466.38 and the chemical formula is Ci,iHj,N.Na,0,S2. Its molecular struc-Na OjS Figure 1 The molecular structure of indigo carmine SOjNa ture is shown in Fig 1. Until the pres-sor effect was noted recently, it had been regarded as pharmacologically inactive. Erickson and Widner" noted that indigo carmine structurally resembles two molecules of 5-hydroxytryptamine, or serotonin.' See Fig 2. H H -C—C—H H NH, Figure 2 The molecular structure of serotonin The cardiovascular effects of sero-tonin in man are complex." Its vaso-pressor action is thought to be due largely to an increase in total peripheral resistance and in cardiac output, al-though chemoreceptor stimulation also plays a part.^° Kennedy et aP observed definite increase in total peripheral 133 Wu and Johnson resistance after administration of in-digo carmine.'" The cardiovascular ef-fects of serotonin are quite similar to those of indigo carmine, and therefore, their resemblance in structure may be significant. However, we did not ob-serve the cutaneous flush and blotchy cyanosis that has been noted with serotonin in patients who received in-digo carmine. This cutaneous change with serotonin results from constriction of peripheral arterioles with dilatation of minute vessels of the skin.^ ^ Increases in blood pressure were more pronounced, and the period of vasopressor effect was more prolonged, in Group I patients. The vasoconstric-tion from serotonin is more pronounced and prolonged in the absence of sym-pathetic vasomotor activity, A simflar phenomenon may account for the more sustained vasopressor effects of indigo carmine in anesthetized patients. No allergic reaction was encountered in our series. A nearly fatal reaction to only 0.75 cc of indigo carmine was reported by Schwerin, however.^ ^ Serotonin releases histamine from the skin of the cat, and antihistaminic agents can inhibit the vascular response to serotonin." Whether indigo carmine acts in this manner remains to be proved, but, if so, antihistamines may prevent vascular reactions during the employment of indigo carmine. Summary The vasopressor effect of indigo carmine has been studied in anes-thetized as well as in unanesthetized patients. Elevation of blood pressure and bradycardia were noted in aU cases. The reasons for this vasopressor effect and its implications are discussed. Indigo carmine is a useful and gen-erally safe agent. It should be admin-istered with caution, however, in the markedly hypertensive and cardiac patients. REFERENCES 1. Thomas, B. A., and Birdsall, J. C: Comparative results of various functional kidney tests, JAMA 69:1747-52, 1917. 2. Herman, L.: The Practice of Urology, Philadelphia: W. B. Saunders Co., 1938, p 39. 3. McCrea, L. E.: Clinical Urology; Essentials of Diagnosis and Treatment, ed 2, Philadel-phia: F. A. Davis Co., 1948. 4. Lacy, W. W.; Ugaz, C; and Newman, E. V.: The use of indigo carmine for dye dilution curves, CiVc Res 3:570-4, Nov 1955. 5. Song, J. E., and Kim, S. K.: The use of indigo carmine in ureteral operations, / Urol 98:669-70, Dec 1967. 6. Lowsley, O. S., and Kirwin, T. J.: Clinical Urology, Baltimore: Williams & Wilkins Co., 1940, p 45. 7. Erickson, J. C, and Widmer, B. A.: The vasopressor effect of indigo carmine, work in progress. Anesthesiology 29:188-9, Jan-Feb 1968. 8. Kennedy, W. F., Jr., et al: Cardiovascular and respiratory effects of indigo carmine, J Urol 100:775-8, Dec 1968. 9. Haverback, B. J.; Stubrin, M. I . ; and Majcher, S. J.: Serotonin and related substances, DM 3-40, Apr 1966. 10. Douglas, W. W.: S-Hydroxytryptamine and antagonists; polypeptides—angiotensin and kinins, in Goodman, L. S., and Gilman, A. (eds): The Pharmacological Basis of Therapeutics, ed 3, New York: Macmillan Co., 1965, p 647. 11. Shiffman, M. A., and Rappaport, I.: Carcinoid tumors and serotonin physiology, Amer Surg 31:615-20, Oct 1965. 12. McCubbin, J. W.: A vexing hormone—serotonin, Cleveland Clin Quart 29:73-5, Apr 1962. 13. Schwerin, G. S.: Severe reaction to indigo-carmine, Ilinois Med J 101:48-9, Jan 1952. 134 

The Vasopressor Effect of Indigo Carmine

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The Vasopressor Effect of Indigo Carmine

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