Avaliação do hidroxietilamido de terceira geração (Tetrastarch) em relação ao Ringer Lactato como fluido de reposição volêmica em cães submetidos à hemodiluição normovolêmica aguda
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Data
2017-02-24
Autores
Diniz, Miriely Steim [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Justificativa: Coloides sintéticos como o “Tetrastarch“ (TS), quando comparados aos cristaloides isotônicos, são expansores volêmicos mais eficazes e minimizam o risco de edema tecidual. Entretanto, o TS pode causar efeitos adversos sobre a coagulação e, em pacientes sépticos, pode aumentar o risco de injúria renal aguda e morte. Hipóteses: Formularam-se as hipóteses de que, em cães sadios, a HNA com TS não resultaria em evidência de IRA; enquanto que a inibição da coagulação induzida por este coloide seria ao menos equivalente a produzida pelo Ringer Lactato (RL). A HNA com TS, quando comparada a HNA com RL, resultaria em menor acúmulo de água extravascular pulmonar e menor incidência de edema periférico. Materiais e Métodos: Seis cães (19,7–35,3 kg) foram anestesiados durante 7 horas com isoflurano/remifentanil em 3 ocasiões. Na primeira ocasião (Fase I), os animais não foram submetidos a HNA (controle). Na Fase II, iniciada após intervalo > 2 semanas do término da Fase I, os cães foram anestesiados em 2 ocasiões para realização de HNA, em um modelo experimental randomizado (intervalo > 8 semanas). Em cada procedimento, o sangue removido foi reposto com RL ou TS, (3 mL de RL ou 1 mL de TS para cada 1 mL de sangue removido), durante 60 minutos, visando reduzir o hematócrito para 33%. A anestesia foi mantida por 4 horas após a reposição volêmica (RV). As variáveis cardiorrespiratórias foram coletadas no momento BL (basal, antes da HNA), 0,5, 1, 2, 3 e 4 horas após a RV. Os biomarcadores de IRA (NGAL, creatinina) foram mensurados no momento BL, 4, 24 e 72 horas após a RV. A hemostasia foi avaliada no momento BL, 0,5, 2, 4 e 24 horas após a RV. Resultados: No tratamento TS, o índice de água extravascular pulmonar (EVLWI), observado a 1 hora após a RV, foi significativamente menor (P < 0,05) em relação ao controle. As 4 horas após a RV, o EVLWI no tratamento TS foi significativamente menor em comparação ao tratamento RL. A relação pressão parcial de oxigênio arterial/fração inspirada de oxigênio não diferiu entre tratamentos (P > 0,05) entre 0,5–4 horas após a RV. Edema de cabeça foi observado em 3/6 cães somente no tratamento RL. A relação lipocalina associada a gelatinase neutrofílica/creatinina urinária não diferiu entre os tratamentos e manteve-se abaixo do limite para detecção de IRA (120.000 pg/mg) durante 72 horas após a RV. O tempo de formação do coágulo aumentou significativamente em relação ao controle por um período mais prolongado no tratamento RL (entre 0,5–4 horas após a RV) do que no tratamento TS (entre 0,5–2 horas após a RV). A firmeza máxima do coágulo se reduziu significativamente em relação ao controle por um período idêntico para ambos os fluidos (entre 0,5–4 horas após a RV). Não foram detectadas diferenças significativas no tempo de sangramento de mucosa oral após a RV. Conclusões: O TS, quando empregado em cães saudáveis submetidos a HNA, além de não produzir evidência de IRA, causa coagulopatia dilucional transitória de forma semelhante ao RL. O emprego do TS como fluido de reposição volêmica na HNA é preferido em relação ao RL, uma vez que este coloide resulta em menor acúmulo de água extravascular pulmonar que o RL e não produz evidência de edema periférico.
Rationale: Synthetic colloids such as tetrastarch solution (TS), when compared to crystalloids, are more effective plasma expanders and minimize the risk of edema. However, TS may cause adverse effects on coagulation and, in septic patients, may increase the risk of acute kidney injury (AKI) and death. Hypotheses: The first hypothesis was that, in healthy dogs, acute normovolemic hemodilution (ANH) with TS would not induce AKI; while the coagulation impairment induced by this colloid would be at least equivalent to that induced by lactated Ringer´s solution (LRS). The second hypothesis was that ANH with TS, when compared to ANH with LRS, would cause less extravascular lung water accumulation and less evidence of peripheral edema. Material and Methods: Six dogs (19.7–35.3 kg) were anesthetized with isoflurane/remifentanil on 3 occasions. During the first occasion (Phase I), animals did not undergo ANH (control). During Phase II, initiated after an interval of at least 2-weeks, the same dogs underwent anesthesia for ANH on 2 occasions, in a ramdomized crossover design (washout interval > 8-weeks). During both procedures, the blood withdrawn was replaced with LRS or TS (3 mL of LRS or 1 mL of TS for each 1 mL of blood removed), during 60 minutes, aiming to decrease the hematocrit to 33%. Anesthesia was maintained for 4 hours after volume replacement (VR). Cardiorespiratory variables were recorded at BL (before ANH), 0.5, 1, 2, 3, and 4 hours after VR. Biomarkers of AKI were measured at BL, 4, 24, and 72 hours after ANH. Hemostasis was assessed at BL, 0.5, 2, 4, and 24 hours after VR. Results: In the TS treatment, the extra-vascular lung water index (EVLWI) observed 1 hour after VR was significantly smaller (P < 0.05) than in controls. At 4 hours after VR, the EVLWI in the TS treatment was significantly smaller than in the LRS treatment. The arterial oxygen partial pressure/inspired oxygen fraction ratio did not differ among treatments (P > 0.05) between 0.5–4 hours after VR. Head edema was observed in 3/6 dogs in the LRS treatment only. The Neutrophil gelatinase-associated lipocalin/creatinine ratio in urine did not differ among treatments and was lower than the threshold for detecting AKI (120.000 pg/mg) during 72 hours after VR. Clot formation time significantly increased from controls for a longer period in the LRS treatment (between 0.5–4 hours after VR) than in the TS treatment (between 0.5–2 hours after RV). Maximum clot firmness significantly decreased from controls for the same time period for both fluids (between 0.5–4 hours after VR). No significant differences were found for buccal mucosal bleeding time after VR. Conclusions: The use of TS in healthy dogs undergoing ANH, in addition to not producing evidence of AKI, causes a transient dilutional coagulopathy that is at least similar to that produced by ANH with LRS. In as much as TS results in less extra-vascular lung water accumulation than LRS, and does not produce evidence of peripheral edema, the use of TS as a volume replacement fluid in the ANH setting is favored in comparison to LRS.
Rationale: Synthetic colloids such as tetrastarch solution (TS), when compared to crystalloids, are more effective plasma expanders and minimize the risk of edema. However, TS may cause adverse effects on coagulation and, in septic patients, may increase the risk of acute kidney injury (AKI) and death. Hypotheses: The first hypothesis was that, in healthy dogs, acute normovolemic hemodilution (ANH) with TS would not induce AKI; while the coagulation impairment induced by this colloid would be at least equivalent to that induced by lactated Ringer´s solution (LRS). The second hypothesis was that ANH with TS, when compared to ANH with LRS, would cause less extravascular lung water accumulation and less evidence of peripheral edema. Material and Methods: Six dogs (19.7–35.3 kg) were anesthetized with isoflurane/remifentanil on 3 occasions. During the first occasion (Phase I), animals did not undergo ANH (control). During Phase II, initiated after an interval of at least 2-weeks, the same dogs underwent anesthesia for ANH on 2 occasions, in a ramdomized crossover design (washout interval > 8-weeks). During both procedures, the blood withdrawn was replaced with LRS or TS (3 mL of LRS or 1 mL of TS for each 1 mL of blood removed), during 60 minutes, aiming to decrease the hematocrit to 33%. Anesthesia was maintained for 4 hours after volume replacement (VR). Cardiorespiratory variables were recorded at BL (before ANH), 0.5, 1, 2, 3, and 4 hours after VR. Biomarkers of AKI were measured at BL, 4, 24, and 72 hours after ANH. Hemostasis was assessed at BL, 0.5, 2, 4, and 24 hours after VR. Results: In the TS treatment, the extra-vascular lung water index (EVLWI) observed 1 hour after VR was significantly smaller (P < 0.05) than in controls. At 4 hours after VR, the EVLWI in the TS treatment was significantly smaller than in the LRS treatment. The arterial oxygen partial pressure/inspired oxygen fraction ratio did not differ among treatments (P > 0.05) between 0.5–4 hours after VR. Head edema was observed in 3/6 dogs in the LRS treatment only. The Neutrophil gelatinase-associated lipocalin/creatinine ratio in urine did not differ among treatments and was lower than the threshold for detecting AKI (120.000 pg/mg) during 72 hours after VR. Clot formation time significantly increased from controls for a longer period in the LRS treatment (between 0.5–4 hours after VR) than in the TS treatment (between 0.5–2 hours after RV). Maximum clot firmness significantly decreased from controls for the same time period for both fluids (between 0.5–4 hours after VR). No significant differences were found for buccal mucosal bleeding time after VR. Conclusions: The use of TS in healthy dogs undergoing ANH, in addition to not producing evidence of AKI, causes a transient dilutional coagulopathy that is at least similar to that produced by ANH with LRS. In as much as TS results in less extra-vascular lung water accumulation than LRS, and does not produce evidence of peripheral edema, the use of TS as a volume replacement fluid in the ANH setting is favored in comparison to LRS.
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Palavras-chave
Cães, Coagulação, Coloides, Lesão renal aguda, Transfusão de sangue, Acute kidney injury, Autologous blood transfusion, Coagulation, Colloids, Dog