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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.55 no.2 Campinas Mar./Apr. 2005
Cardiovascular and renal effects of intra-arterial injection of ionic radiological contrast in dogs under fluid restriction*
Efectos cardiovasculares y renales de la inyección intra-arterial de contraste radiológico iónico en perros con restricción hídrica
Marisa Aparecida Lima Verderese, M.D.I; Pedro Thadeu Galvão Vianna, TSA, M.D.II; Yara Marcondes Machado Castiglia, TSA, M.D.II; Luiz Antonio Vane, TSA, M.D.II
IPós-Graduanda do Departamento de
Anestesiologia da Faculdade de Medicina da UNESP, Campus de Botucatu, nível
IIProfessor Titular do CET/SBA do Departamento de Anestesiologia da Faculdade de Medicina da UNESP, Campus de Botucatu
BACKGROUND AND OBJECTIVES: This study
aimed at evaluating acute radiological contrast effects in fluid restriction
situations, observing renal and cardiovascular effects after intra-arterial
injection of high osmolarity radiological contrast.
METHODS: Participated in this study 16 dogs anesthetized with sodium thiopental (15 mg.kg-1) and fentanyl (0.03 mL.kg-1), followed by continuous infusion of 40 µg.kg-1.min-1 (sodium thiopental) and 0.1 µg.kg-1.min-1 (fentanyl). Hydration was achieved with 5% glucose solution (0.03 mL.kg-1.min-1) and ventilation was mechanically controlled with compressed air. The following attributes were evaluated: heart rate (HR); mean blood pressure (MBP); inferior vena cava pressure (IVP); cardiac output (CO); hematocrit (Ht); effective renal plasma flow (ERPF); renal blood flow (RBF); glomerular filtration rate (GFR); filtration fraction; renal vascular resistance (RVR), urinary volume (UV); plasma and urinary osmolarity; osmolar clearance; free water clearance; sodium and potassium clearance; plasma sodium and potassium; sodium and potassium urinary fractional excretion and rectal temperature. These attributes were evaluated in four moments: 30 (M1), 60 (M2), 90 (M3) and 120 (M4) minutes after sodium para-aminohipurate and creatinine administration (beginning of experiment). In moment 2, G1 received intra-arterial 0.9% saline (1.24 mL.kg-1) and G2 received intra-arterial radiological contrast (1.4 mL.kg-1).
RESULTS: Group G1 has presented increased HR, ERPF, RBF, plasma osmolarity, sodium clearance and sodium urinary excretion, in addition to decreased urinary osmolarity, plasma sodium, potassium clearance and rectal temperature. Group G2 has presented increased HR, RVR, UV, osmolar clearance, sodium clearance and sodium urinary and fractional excretion; there has also been decrease in hematocrit, glomerular filtration rate, filtration fraction, urinary osmolarity, free water clearance, urinary sodium and potassium, plasma potassium and rectal temperature.
CONCLUSIONS: This study has concluded that intra-arterial radiological contrast has promoted a two-phase effect on renal function. Initially it has promoted increased diuresis and sodium excretion but then the hemodynamic conditions impaired, and consequently renal function impaired, with increased renal vascular resistance and decreased glomerular filtration rate.
Key words: ANIMALS: dogs; CARDIOVASCULAR SYSTEM; hemodynamic; CONTRAST MEDIA; KIDNEY: function
JUSTIFICATIVA Y OBJETIVOS: El objetivo
de esta pesquisa fue estudiar los efectos agudos del contraste radiológico en
situaciones de restricción de volumen, evaluándose los efectos renales y cardiovasculares
después de inyección intra-arterial de contraste radiológico de alta osmolaridad.
MÉTODO: Participaron del estudio 16 perros anestesiadas con tiopental sódico (15 mg.kg-1) y fentanil (15 µg.kg-1) en bolus, seguido de infusión continuada en las dosis de 40 µg.kg-1.min-1 (tiopental sódico) y 0,1 µg.kg-1.min-1 (fentanil). Fue hecha hidratación con solución de glucosa a 5% (0,03 mL.kg-1.min-1) y la ventilación pulmonar fue controlada mecánicamente con aire comprimido. Fueron verificados los siguientes atributos: frecuencia cardiaca (FC); presión arterial media (PAM); presión de la vena cava inferior (PVI); débito cardíaco (DC); hematocrito (Ht); flujo plasmático efectivo renal (FPER); flujo sanguíneo renal (FSR); ritmo de filtración glomerular (RFG); fracción de filtración; resistencia vascular renal (RVR); volumen urinario (VU); osmolaridad plasmática y urinaria; depuración osmolar, depuración de agua libre y depuración de sodio y de potasio; sodio y potasio plasmáticos; excreción urinaria y fraccionaria de sodio y potasio y temperatura rectal. Estos atributos fueron evaluados en cuatro momentos: 30 (M1), 60 (M2), 90 (M3) y 120 (M4) minutos después del inicio de la infusión de para-aminohipurato de sodio y creatinina (inicio de la experiencia). En el momento 2, en el grupo G1 fue dada una inyección intra-arterial de solución fisiológica a 0,9% (1,24 mL.kg-1), y en el grupo G2 fue inyectado contraste radiológico (1,24 mL.kg-1) por la misma vía.
RESULTADOS: El grupo G1 presentó aumento de la FC, del FPER, del FSR, de la osmolaridad plasmática, de la depuración de sodio y de la excreción urinaria de sodio; presentó aún disminución de la osmolaridad urinaria, del potasio plasmático, de la depuración de potasio y de la temperatura rectal. En el grupo G2 ocurrió aumento de la FC, de la RVR, del VU, de la depuración osmolar, de la depuración de sodio y de la excreción urinaria y fraccionaria de sodio; ocurrió también reducción del (a): hematócrito ritmo de filtración glomerular, fracción de filtración, osmolaridad urinaria, depuración de agua libre, sodio y potasio urinarios, potasio plasmático y temperatura rectal.
CONCLUSIONES: En este estudio, se concluye que, la inyección intra-arterial del contraste radiológico causó efecto bifásico en la función renal. Inicialmente, provocó aumento de la diuresis y de la excreción de sodio, pero, posteriormente, hubo empeoramiento de las condiciones hemodinámicas y, consecuentemente, de la función renal, con aumento de la resistencia vascular renal y disminución del ritmo de filtración glomerular.
Radiological contrast administration is still one of the most common iatrogenic causes of acute renal failure acquired in the hospital 1-4. Although the pathogenesis of such condition is still not totally understood, it seems to be due to medullary ischemia caused by decreased renal blood flow 1-4.
Intravenous fluids, mannitol and furosemide, have been recommended to prevent radiological contrast-induced nephropathy, but the efficacy them has not yet been proven 5. Recently, intravenous acetylcysteine (150 mg.kg-1) 30 minutes before radiological contrast administration has been indicated, followed by 50 mg.kg-1 four hours after radiological procedure. Both acethylcystein doses were diluted in 500 mL saline. Results have shown renal protection against nephrotoxicity caused by radiological contrast.
The incidence of nephropathy by radiological contrast may reach much higher values In the presence of predisposing factors, among them: dehydration, diabetes mellitus, multiple mieloma, advanced age, heart disease, use of diuretics, renal failure and exams with radiological contrast performed in short time periods 2,8,9.
Radiological contrast during anesthesia may be intra-arterially injected for diagnostic purposes. So, the understanding of acute and immediate effects of radiological contrast on major renal functions is critical.
This study aimed at evaluating acute effects of radiological contrast in fluid restriction states. For this purpose, the experiment was performed with dogs under fluid restriction to evaluate immediate renal and cardiovascular effects after intra-arterial injection of high osmolarity radiological contrast.
After the Animal Experiment Ethics Committee, Faculdade de Medicina, Botucatu, UNESP approval, 16 male, adult, mixed-breed dogs weighing 7 to 17 kg and supplied by the Central Lab Animals Facility, UNESP, were involved in this study. Anesthesia was induced with sodium thiopental (15 mg.kg-1), fentanyl (15 µg.kg-1), and alcuronium (0.2 mg.kg-1), followed by 40 µg.kg-1.min-1 sodium thiopental and 0.1 µg.kg-1 min-1 fentanyl in continuous infusion throughout the experiment. Moment 1 (control) was defined as 30 minutes after sodium para-aminohipurate (PAH) and creatinine infusion. Moments 2 (M2), 3 (M3) and 4 (M4) were defined as 30, 60 and 90 minutes after 0.9% saline (Group 1) or radiological contrast injection (Group G 2). Each study period lasted 30 minutes.
This was a double-blind study and animals were randomly distributed in two experimental groups: Group 1 - G1 - control, SS, and Group 2 - G2 - high intensity ionic radiological contrast (meglumine diatrizoate and sodium). To start moment 2 (M2) animals received 1.24 mL.kg-1 intra-arterial saline (Group 1) or radiological contrast (Group 2).
The following experimental sequence was performed for all animals: feed and fluid restriction for 12 hours; weighing; anesthetic induction; dog placement and fixation on Claude Bernard device; tracheal intubation; controlled ventilation with compressed air, using K. Takaoka model 850-10 anesthesia machine; blood vessels dissection; hydration (0.03 mL.kg-1.min-1); anesthesia (continuous infusion for maintenance); thoracotomy in the 4th intercostal space to place the flowmetric probe in the initial portion of ascending aorta, adaptation and calibration of electromagnetic flowmeter (Blood Flowmeter) - Gould Statham model SP 2202; injection of initial PAH and creatinine dose (1 mL.kg-1 of 0.4% PAH and 3% creatinine) followed by 1.6% PAH and 4% creatinine continuous infusion in 5% glucose solution (0.015 mL.kg-1.min-1); all animals received supplemental alcuronium (0.06 mg.kg-1). At experiment end animals were sacrificed with potassium chloride. The following attributes were evaluated: mean blood pressure (MBP); heart rate (HR); inferior vena cava pressure (IVCP); renal blood flow (RBF); cardiac output (CO); hematocrit (Ht); creatinine clearance - glomerular and PAH filtration rate - effective renal plasma flow (ERPF); renal vascular resistance (RVR); sodium, potassium, and plasma and urinary osmolality; rectal temperature (ºC).
At experiment end, fragments of the left kidney were removed for histological exam. These fragments were formalin fixed processed for inclusion in paraffin and stained with hematoxylin-eosin. Sections were examined by the pathologist who diagnosed type and intensity of pathological injury.
Mean (x) and standard deviation (s) were calculated for each variable in each moment and fully randomized factorial analysis of variance was used with the following tests: interaction between group and moment, group effect and moment effect. In all tested hypothesis, F were considered significant when p < 0.05. Contrasts between pairs of means were analyzed by Tukey's test, with calculation of minimum significant difference for alpha = 0.05.
Groups were homogeneous in weight and gender.
There has been significant increase in heart rate (Table I), sodium clearance (G1 < G2 in M3 and M4) (Table II) and sodium urinary excretion (G1 < G2 in M2, M3 and M4) (Table II) for both groups. There has also been significant decrease in urinary osmolality (Table II), urinary volume and plasma potassium (G1 < G2 in M3 and M4) (Table II) for both groups.
Control group (G1) had significant increase in effective renal plasma flow (Table I), renal blood flow (Table I) and plasma osmolality (Table II), and significant decrease in potassium clearance (Table II).
Radiological contrast infusion (G2) has promoted significant increase in cardiac output, renal vascular resistance (Table I), osmolar clearance (G1 < G2 in M3 and M4) (Table II) and sodium fractional excretion (G1 < G2 in M3 and M4) (Table II). It has also promoted decrease in hematocrit (Table I), glomerular filtration rate (Table I), filtration fraction (Table I) and free water clearance (G1 < G2 in M3 and M4) (Table II).
In both groups there were animals with normal histological analysis or with interstitial mononuclear inflammatory infiltrate in renal cortical, or else, tubular necrosis focuses evidenced by karyolysis areas.
Sodium thiopental and fentanyl were administered in continuous infusion to provide uniform conditions throughout the experiment, preventing both overdose and concentrations below therapeutic levels. Urinary osmolality has decreased for both groups soon after saline or radiological contrast infusion, but its values remained high. These high osmolality values have shown that fluid restriction was enough to promote extracellular volume contraction.
Some studies have shown temporary hypertension after radiological contrast injection 10-11. There have been no changes in this parameter in our study, similar to another study 12, but there was increased heart rate and urinary output. There has been temporary hematocrit decrease after radiological contrast infusion. This result has been also observed by different studies 9,13,14, and may be attributed to the osmotic effect of the solution in the contrast.
There are reports 15,16 proving RBF and ERPF increase in dogs anesthetized with fentanyl. In both groups, there has been temporary RBF and ERPF increase which was however significant only for the 0.9% saline group. Possible explanation for our results would be the anesthetic technique. While previous studies have used bolus injection, we have used fentanyl in continuous infusion.
Temporary increase in RBF and GFR after 2 or 4 mL.kg-1 contrast have been shown 17. After 8 mL.kg-1, no changes in RBF were found, but there has been decrease in GFR. In our study, GFR has also decreased. As to RBF, different results may be attributed to different methods used by both studies. While the first study 17 evaluated RBF by flowmetric method, our research has used PAH clearance method. In the flowmetric technique, results is immediate, while with the clearance method, result is the mean of what has happened during 30 minutes.
In this latter method, fugacious results with low clinical significance are not detected. In agreement with this study, a different study 12 has not found RBF changes but has observed GFR decrease after radiological contrast injection. In our study, there have been RBF decrease and RVR increase after contrast injection, being significant in the final moment and showing that contrast injection has promoted only late changes.
FF has temporarily decreased after radiological contrast and similar result was obtained by Katzberg et al. 18. Several studies have also shown decreased creatinine clearance after low or high osmolality radiological contrast 3,19,20, or also temporary decrease of this parameter after contrast 19,21. Some authors have used plasma creatinine (PCr) as parameter for evaluating renal function. There has been PCr increase when radiological contrast was simultaneously administered with furosemide 22,23 or mannitol 23, in patients with normal or increased baseline PCr 3 and in patients with renal failure alone or associated to diabetes mellitus 24. A different study has shown that PCr was not significantly changed after radiological contrast 25. The difference in those studies might have been hydration, of there might have been GFR decrease although not so significant to increase PCr.
Another hypothesis to explain radiological contrast effects on renal hemodynamics would be the possibility of hyperosmotic solutions stimulating rennin-angiotensin system 28. It has been shown 29 that hypertonic solutions injected in the renal artery of dogs would promptly promote major increase in rennin release.
UV and Cosm have significantly increased soon after radiological contrast injection, but Cosm has returned to baseline levels at the end of the experiment. There has also been temporary CH2O decrease.
Literature is controversial with regard to urinary volume since there are studies 19,30 showing its decrease after radiological contrast, while others 10,12,13 have shown increase in this parameter, similarly to our study. Also in line with our study, a different research 13 has shown increased Cosm after radiological contrast injection.
Both groups have shown increased CNa+, UENa+ e PK+ while in the radiological contrast group there has also been increased FENa+ and decreased UNa+ and UK+. The two latter could be explained by osmotic diuresis-induced dilution. Some studies, in agreement with ours, have shown increased UENa+ 12,31,32 and FENa+ 32 after ionic and non-ionic radiological contrast, which seems to be independent of contrast osmolality. Increased sodium excretion cannot be explained by sodium content in radiological contrast: diatrizoate has high sodium concentration, while ioxilan, iopamidol, iohexol and other low osmolality contrasts have very low concentrations of this electrolyte. A possible explanation for increased sodium urinary excretion could be osmotic diuresis promoted by all radiological contrasts, regardless of sodium content and of radiological contrast being or not hyperosmotic.
Potassium is primarily excreted by kidneys and the rate is a direct function of this ion overload in the body. Also, when sodium is too high in the tubular lumen, there is sodium entrance in the tubular cell and sodium pump stimulation with potassium entering the cell and then being excreted in the tubular lumen 33. This may explain decreased plasma potassium in the two final moments in both groups in our experiment.
There has been no difference between groups in pathological findings. Both groups presented normal histological analysis or interstitial inflammatory infiltrate of mild to severe intensity or tubular necrosis focuses.
One of the first studies performed in our Department 34 has found, in most dogs, histological changes compatible with chronic pyelonephritis. The author has concluded that, in dogs, chronic pyelonephritis is a frequent pathological diagnosis. Similar pathological result obtained for both groups has shown that there were no radiological contrast-induced renal injuries.
So, in the conditions of this study, intra-arterial radiological contrast in animals with decreased extracellular volume has promoted a two-phase effect on renal function. Initially it promoted increased diuresis and sodium excretion, but then the hemodynamic conditions impaired and, as a consequence, renal function impaired, with increased renal vascular resistance and decreased glomerular filtration rate.
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Submitted for publication September 17, 2004
Accepted for publication January 6, 2005
* Received from Departamento de Anestesiologia da Faculdade de Medicina de Botucatu, UNESP, Botucatu, SP