Mechanisms of tissue hypoperfusion in experimental sepsis and effects of volume resuscitation with hypertonic-isoncotic saline solution and pentoxiphylline

Author(s)

Carolinne Torres Silva Dias

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2011-05-24

Examining board members

Mauricio da Rocha e Silva; Alejandra Del Pilar Gallardo Garrido; Denise Aya Otsuki; Reinaldo Salomão; Angelo João Stopiglia

• Advisor: Mauricio da Rocha e Silva

Abstract

The septic shock hemodynamic instability has as major component the reduction of tissue perfusion, which is known to aggravate morbidity and mortality. Knowing this, the early and correct choice of therapy to be instituted, including the type and time of fluid inoculation is an important step to help increase the survival rate of these patients. Thus, this experiment was designed to better understand the macro and micro-hemodynamic events of this syndrome, in order to verify the perfusion effects of early treatment with hypertonic-isoncotic saline solution and pentoxiphylline in septic shocked pigs. We studied the effects of hypertonic-isoncotic saline solution (Hyperhaes ®) compared to its association or not to pentoxiphylline, and compared to crystalloid Ringer lactate. We used 29 male and female pigs of 29kg on average. Septic shock was induced by an intravascular solution (0.6 x 1010 cfu/kg) of an enteropathogenic strain (O55) of Escherichia coli for 60 minutes. The animals were observed without intervention for 30 minutes and treatment was chosen randomly: group Ringer lactate (32ml/kg in 20 minutes, n = 9); hypertonic-isoncotic saline solution (4 ml/kg in 5 minutes, n = 7); hypertonic-isoncotic saline solution with pentoxiphylline (4ml/kg and 25mg/kg, respectively, in 5 minutes, n = 8) and Control group (no treatment, n = 5). The animals received maintenance fluid (10 ml/kg/hour 0.9% saline solution) without any other intervention than the treatments of each group during the evaluation period. Hemodynamic, ventilation and oxygenation assessments were performed. The mixed venous oxygen saturation was observed at 120 and 150 minutes and when it was below 70% a new fluid therapy was given (HSPTX and HS groups received 32 ml/kg of saline solution 0.9% in 20 minutes and RL group 32 ml/kg Ringer\'s lactate also in 20 min.). Tissue samples of the heart, lungs, jejunum, colon, liver and kidneys were collected for histopathological examination and kept in 10% buffered formaldehyde. Inoculation of E. coli resulted in a state of rapid and progressive hemodynamic deterioration with pulmonary hypertension and its consequent cardiac dysfunction (low cardiac output and ejection fraction). There was, in all groups, a progressive reduction of mean arterial pressure that stabilized close to 50 mmHg at 90 minutes, with the mean pulmonary arterial pressure following the same trend. In relation to systemic vascular resistance index, over time, there was a significant differentiation between HSPTX and Control groups (p 0.01) and Control and RL groups (p 0.05), with the Control group values above the others. In the rate of portal blood flow there was significant difference between HS and RL groups over time (p 0.05) (decline of 2.08 ml/min. by HS group when compared to RL group). HSPTX and RL groups showed a significant behavior difference (p < 0.001) over time in their lactate levels, with the group HSPTX increasing their values 0.02 mmol/dl/min in relation to the RL group. Both HSPTX and HS groups dropped the veno-arterial gradient of CO2 in relation to the RL and Control groups (-0.08 to -0.05 mmHg / min.). However, there was an increase in the jejunum-arterial gradient of CO2 values on HSPTX and HS groups compared to RL (0.01 and 0.04 mmHg / min., respectively). The mixed venous oxygen saturation had a decreasing in its values during the bacteria infusion in all groups, but only the HS and HSPTX groups, after treatment, showed improvement in their levels (above 70%), nevertheless, there was no statistical difference among groups. HS and HSPTX solutions proved to be options for targeted therapies in the early phase of sepsis in pigs, although exist the need of more research to find out the origin of high lactate levels in the HSPTX group (AU)