ABSTRACT
BACKGROUND: Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited. METHODS: At 18 centers, we randomly assigned patients who presented with acute pancreatitis to receive goal-directed aggressive or moderate resuscitation with lactated Ringer's solution. Aggressive fluid resuscitation consisted of a bolus of 20 ml per kilogram of body weight, followed by 3 ml per kilogram per hour. Moderate fluid resuscitation consisted of a bolus of 10 ml per kilogram in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 ml per kilogram per hour in all patients in this group. Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to the patient's clinical status. The primary outcome was the development of moderately severe or severe pancreatitis during the hospitalization. The main safety outcome was fluid overload. The planned sample size was 744, with a first planned interim analysis after the enrollment of 248 patients. RESULTS: A total of 249 patients were included in the interim analysis. The trial was halted owing to between-group differences in the safety outcomes without a significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; adjusted relative risk, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P = 0.32). Fluid overload developed in 20.5% of the patients who received aggressive resuscitation and in 6.3% of those who received moderate resuscitation (adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94, P = 0.004). The median duration of hospitalization was 6 days (interquartile range, 4 to 8) in the aggressive-resuscitation group and 5 days (interquartile range, 3 to 7) in the moderate-resuscitation group. CONCLUSIONS: In this randomized trial involving patients with acute pancreatitis, early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes. (Funded by Instituto de Salud Carlos III and others; WATERFALL ClinicalTrials.gov number, NCT04381169.).
Subject(s)
Acid-Base Imbalance , Fluid Therapy , Pancreatitis , Water-Electrolyte Imbalance , Acid-Base Imbalance/etiology , Acid-Base Imbalance/therapy , Acute Disease , Fluid Therapy/adverse effects , Fluid Therapy/methods , Humans , Pancreatitis/complications , Pancreatitis/therapy , Resuscitation/methods , Ringer's Lactate/administration & dosage , Ringer's Lactate/therapeutic use , Water-Electrolyte Imbalance/etiology , Water-Electrolyte Imbalance/therapyABSTRACT
En este trabajo se realizó la evaluación toxicológica a dosis repetidas por el método de test límite del candidato ainmunopotenciador, la solución CM-95 tratada magnéticamente, acorde con las regulaciones de la Organización para la Colaboración Económica y el Desarrollo, incluida en la Guía 407. El objetivo fue establecer las posibles lesiones orgánicas y funcionales ocasionadas por la solución CM-95, tratada magnéticamente con la máxima inducción magnética permisible (0,16 T), para la obtención del candidato a inmunopotenciador. Se emplearon tres grupos: Experimental, Control y Satélite. Como Biomodelo experimental se utilizaron ratas Sprague Dawley machos y hembras con pesos de 150 a 200 g. Durante el estudio no se registraron signos clínicos de toxicidad ni muertes en ninguno de los animales de los grupos tratados, ni en los controles. No hubo afectación del peso corporal durante elensayo. Aunque hubo variaciones en los valores de algunos parámetros hematológicos y bioquímicos, estos no tuvieron significación biológica. No se encontraron lesiones macroscópicas, ni microscópicas; solo se observaron efectos proliferativos en el tejido linfoide de timo y bazo, relacionados con la respuesta del sistema inmune. Lasolución CM-95 tratada magnéticamente, no mostró toxicidad en el modelo animal y nivel de dosis utilizado, y bajo las condiciones experimentales ensayadas(AU)
In this study the toxicological evaluation at repeated dose by the method of limit test of the candidate to magnetically treated immunopotentiator CM-95 Solution was carried out; according with regulations of the Organization for Economic Cooperation and Development included in guide 407. The objective was to establish the possible organic and functional lesions caused bythe magnetically treated CM-95 Solution with maximum permissible magnetic induction (0,16 T), for obtaining the candidate to immunopotentiator. Three groups were used: Experimental, Control and Satellite. As experimental Biomodels, male and female Sprague Dawley rats were used, with 150 to 200 g weights. During the study neither clinical signs of toxicity nor deathsin any of the animals of the treated groups were registered. There was not affectation of the corporal weight during the test. There was not change of the corporal weight during the trial. Although there were variations of some haematology and biochemical parameters, they had no biological significance. Macroscopic or microscopic lesions were not found; justproliferation effects were observed, in the lymphoid tissues of the thymus and spleen, related to the response of immune system. Magnetically treated CM-95 Solution, showed no toxicity in the animal model and dose level used, and under the observed experimental conditions(AU)
