RESUMO
Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality. Antisecretory factor (AF), an endogenous protein, is detectable in most tissues and in plasma. The biologically active site of the protein is located in an 8-peptide sequence, contained in a synthetic 16-peptide fragment, named AF-16. The protein as well as the peptide AF-16 has multiple modulatory effects on abnormal fluid transport and edema formation/resolution as well as in a variety of inflammatory conditions. Apart from its' anti-secretory and anti-inflammatory characteristics, AF is an inhibitor of capillary leakage in intestine. It is not known whether the protein AF or the peptide AF-16 can ameliorate symptoms in sepsis. We hypothesized that AF-16 decreases the degree of hemodynamic instability, the need of fluid resuscitation, vasopressor dose and tissue edema in fecal peritonitis. To test the hypothesis, we induced peritonitis and sepsis by injecting autologous fecal solution into abdominal cavity of anesthetized pigs, and randomized (in a blind manner) the animals to intervention (AF-16, n = 8) or control (saline, n = 8) group. After the onset of hemodynamic instability (defined as mean arterial pressure < 60 mmHg maintained for > 5 minutes), intervention with AF-16 (20 mg/kg (50 mg/ml) in 0.9% saline) intravenously (only the vehicle in the control group) and a protocolized resuscitation was started. We recorded respiratory and hemodynamic parameters hourly for twenty hours or until the animal died and collected post mortem tissue samples at the end of the experiment. No differences between the groups were observed regarding hemodynamics, overall fluid balance, lung mechanics, gas exchange or histology. However, liver wet-to-dry ratio remained lower in AF-16 treated animals as compared to controls, 3.1 ± 0.4, (2.7-3.5, 95% CI, n = 8) vs 4.0 ± 0.6 (3.4-4.5, 95% CI, n = 8), p = 0.006, respectively. Bearing in mind the limited sample size, this experimental pilot study suggests that AF-16 may inhibit sepsis induced liver edema in peritonitis-sepsis.
Assuntos
Edema/tratamento farmacológico , Peptídeos/farmacologia , Peritonite/complicações , Sepse/complicações , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Edema/complicações , Edema/patologia , Edema/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hemoglobinas/metabolismo , Interleucina-6/sangue , Lactatos/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Peptídeos/uso terapêutico , Projetos Piloto , Troca Gasosa Pulmonar/efeitos dos fármacos , Suínos , Fator de Necrose Tumoral alfa/sangue , Resistência Vascular/efeitos dos fármacosRESUMO
Background: Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with pulmonary capillary leakage and lung oedema formation. There is currently no pharmacologic treatment for the condition. The antisecretory peptide AF-16 reduces oedema in experimental traumatic brain injury. In this study, we tested AF-16 in an experimental porcine model of ARDS.Methods: Under surgical anaesthesia 12 piglets were subjected to lung lavage followed by 2 hours of injurious ventilation. Every hour for 4 hours, measurements of extravascular lung water (EVLW), mechanics of the respiratory system, and hemodynamics were obtained.Results: There was a statistically significant (p = 0.006, two-way ANOVA) reduction of EVLW in the AF-16 group compared with controls. However, this was not mirrored in any improvement in the wet-to-dry ratio of lung tissue samples, histology, inflammatory markers, lung mechanics, or gas exchange.Conclusions: This pilot study suggests that AF-16 might improve oedema resolution as indicated by a reduction in EVLW in experimental ARDS.
Assuntos
Edema/metabolismo , Pulmão/patologia , Peptídeos/farmacologia , Síndrome do Desconforto Respiratório/tratamento farmacológico , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lavagem Broncoalveolar , Modelos Animais de Doenças , Regulação para Baixo , Água Extravascular Pulmonar , Hemodinâmica , Inflamação , Pulmão/efeitos dos fármacos , Troca Gasosa Pulmonar , Respiração Artificial , Síndrome do Desconforto Respiratório/fisiopatologia , SuínosRESUMO
Technological advances in the field of extracorporeal circulation (ECC) over the past decade have led to numerous methods for monitoring metabolism and coagulation during cardiopulmonary bypass (CPB), as well as materials with improved biocompatibility, which has reduced the risk associated with cardiopulmonary bypass. However, ECC is still predominantly based on a traditional design that involves the use of roller pumps. This exposes the patient to a variety of pathophysiological consequences, both intra- and postoperative, such as postoperative cognitive disorders, hemolysis and hemodilution, systemic inflammation and changes in coagulation. This article describes the advantages of an ECC circuit inspired by the Fibonacci Golden Ratio, which does not use a roller pump, in a prospective study on patients undergoing elective cardiac surgery, compared to conventional ECC. During CPB, echocardiography was used to estimate the quality of fluid dynamics in the extracorporeal circuit and the patient's arterial vessels, a DO2 management system was used to evaluate metabolism, and an electronic system was used to determine gaseous microemboli (GME) counts. Fibonacci ECC offered superior intraoperative fluid dynamics, reduced the production of and improved the elimination of GME, and improved intraoperative metabolism, particularly with regard to oxygen delivery and extraction. The improvements in fluid dynamics and metabolic variables were associated with a reduction in the incidence of pathophysiological events compared to the conventional system, particularly regarding transitory cognitive disorders, and a shorter stay in intensive care.