Indigo Carmine Hemodynamic Studies to Treat Vasoplegia Induced by Compound 48/80 in a Swine Model of Anaphylaxis

Abstract

Introduction: There are many reasons to believe that the nitric oxide/guanosine 3'5' - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the investigation rationale.

Methods: The IC (3mg/kg intravenous infusion) study protocol included five experimental groups; 1) Control group - saline was injected at 0 and 10 minutes; 2) IC group - IC was injected at 0 and saline at 10 minutes; 3) compound 48/80 (C48/80) group - C48/80 was injected at 0 minute and saline at 10 minutes; 4) C48/80 + IC group - C48/80 was injected at 0 minute and IC at 10 minutes; and 5) IC + C48/80 group - IC was injected at 0 minute and C48/80 at 10 minutes. The studies were carried out by registering and measuring hemodynamic and blood gasometric parameters, including continuous cardiac output.

Results: 1) The effects of the drugs (IC and C48/80) were more evident in the first 20 minutes of recording; 2) hypotensive responses were more pronounced in the C48/80 groups; 3) IC isolated or applied before C48/80 caused transient pulmonary hypertension; and 4) after the first 20 minutes, the pressure responses showed stability with apparent hypotension more pronounced in the C48/80 groups. Clinical observations showed significant hemodynamic instability and catastrophic anaphylactic reactions (agitation, pulmonary hypertension, severe bronchospasm, urticaria, high-intensity cyanosis, violent gastric hypersecretion, and ascites).

Conclusion: A global results analysis showed differences between groups only in the first 20 minutes of the experiments.

Keywords: Anaphylactic Shock; Anaphylaxis; Indigo Carmine; Methylene Blue; Nitric Oxide; Vasoplegia.

Fig. 1

Blood pressures. Effect of anaphylactic shock caused by compound 48/80 (C48/80) and treated with indigo carmine (IC) in pigs. A) Mean arterial pressure (MAP); B) mean pulmonary arterial pressure (MPAP); C) pulmonary capillary pressure (PCP); D) mean central venous pressure (MCVP). At minute 0, the control (C) group received saline (S), the C48/80 and C48/80 + IC groups received C48/80, the IC and IC + C48/80 groups received IC. At minute 10, the C, IC, and C48/80 groups received S, the C48/80 + IC group received IC, and the IC + C48/80 group received C48/80. Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett post-test (n=5).^*/+/#P<0,05;^**/++/##P<0,01 (*C vs. C48/80 + IC; + C vs. C48/80;^#C vs. IC + C48/80).

Fig. 2

Cardiac output. Effect of anaphylactic shock caused by compound 48/80 (C48/80) and treated with indigo carmine (IC) in pigs. A) Cardiac output (CO); B) cardiac output index (COI). At minute 0, the control (C) group received saline (S), the C48/80 and C48/80 + IC groups received C48/80, the IC and IC + C48/80 groups received IC. At minute 10, the C, IC, and C48/80 groups received S, the C48/80 + IC group received IC, and the IC + C48/80 group received C48/80. Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett post-test (n=5). No statistical difference was observed.

Fig. 3

Vascular resistances. Effect of anaphylactic shock caused by compound 48/80 (C48/80) and treated with indigo carmine (IC) in pigs. A) Systemic vascular resistance (SVR); B) systemic vascular resistance index (SVRI); C) pulmonary vascular resistance (PVR); D) pulmonary vascular resistance index (PVRI). At minute 0, the control (C) group received saline (S), the C48/80 and C48/80+IC groups received C48/80, the IC and IC + C48/80 groups received IC. At minute 10, the C, IC, and C48/80 groups received S, the C48/80 + IC group received IC, and the IC + C48/80 group received C48/80. Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett post-test (n=5). *P<0,05; (*C vs. C48/80+IC).

Fig. 4

Acid-base data. Effect of anaphylactic shock caused by compound 48/80 (C48/80) and treated with indigo carmine (IC) in pigs. A) pH; B) partial pressure of oxygen (pO2); C) Partial pressure of carbon dioxide (pCO2); D) bicarbonate. At minute 0, the control (C) group received saline (S), the C48/80 and C48/80 + IC groups received C48/80, the IC and IC + C48/80 groups received IC. At minute 10, the C, IC, and C48/80 groups received S, the C48/80 + IC group received IC, and the IC + C48/80 group received C48/80. Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett post-test (n=5).^+/#P<0,05;^**/++/##P<0,01;^***/###P<0,001;^****/####P<0,0001 (*C vs. C48/80 + IC; + C vs. C48/80;^#C vs. IC + C48/80).

Fig. 5

Hemoglobin, hematocrit, oxygen saturation and lactate. Effect of anaphylactic shock caused by compound 48/80 (C48/80) and treated with indigo carmine (IC) in pigs. A) Hemoglobin; B) Hematocrit; C) Oxygen saturation (SO2); D) Lactate. At minute 0, the control (C) group received saline (S), the C48/80 and C48/80+IC groups received C48/80, the IC and IC+C48/80 groups received IC. At minute 10, the C, IC and C48/80 groups received S, the C48/80+IC group received IC and the IC+C48/80 group received C48/80. Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett post-test (n=5).⁺ P<0,05;^*/++/## P<0,01;^+++/* P<0,001;^**/#### P<0,0001 (C vs. C48/80+IC; + C vs. C48/80;^#C vs. IC+C48/80).

Fig. 6

Urea, creatinine, and nitrate. Effect of anaphylactic shock caused by compound 48/80 (C48/80) and treated with indigo carmine (IC) in pigs. A) Urea; B) creatinine; C) nitrate. At minute 0, the control (C) group received saline (S), the C48/80 and C48/80 + IC groups received C48/80, the IC and IC + C48/80 groups received IC. At minute 10, the C, IC and C48/80 groups received S, the C48/80 + IC group received IC, and the IC + C48/80 group received C48/80. Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett post-test (n=5).^#P<0,05;^##P<0,01. (^#C vs. IC + C48/80).

Fig. 7

Electrolytes. Effect of anaphylactic shock caused by compound 48/80 (C48/80) and treated with indigo carmine (IC) in pigs. A) Sodium; B) potassium; C) calcium. At minute 0, the control (C) group received saline (S), the C48/80 and C48/80 + IC groups received C48/80, the IC and IC + C48/80 groups received IC. At minute 10, the C, IC, and C48/80 groups received S, the C48/80 + IC group received IC, and the IC + C48/80 group received C48/80. Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett post-test (n=5).^####P<0,0001. (^#C vs. IC + C48/80).