CLUB DE REVISTAS GERMAN GABRIEL CASTILLO RESIDENTE DE ANESTESIOLOGÍA UNIVERSIDAD DEL VALLE TUTOR: DR. FREDY ARIZA

HOSPITAL UNIVERSITARIO DE CIUDAD DEL CABO

INTRODUCCIÓN Existe controversia sobre el uso de los líquidos para la reanimación en trauma Coloides: objetivos circulatorios mas rápido No beneficios en sobrevida Cristaloides Económicos Edema intersticial Síndrome de compartimiento abdominal Controversy persists regarding the choice of fluids for resuscitation in critically injured patients. Colloids are advocated as they are associated with rapid attainment of circulatory goals.1 Crystalloids have been recommended since they are cheaper and no survival benefit has been shown for colloids.2 However, resuscitation with large crystalloid volumes has been associated with complications of tissue oedema and an increased incidence of abdominal compartment syndrome.34 The medium molecular weight hydroxyethyl starch, HES 130/0.4, is a moderate duration colloid with minimal effects on coagulation.5 There has been no extensive study of its use in resuscitation of trauma patients. The need for a well-controlled, carefully conducted, prospective, random- ized, double-blind study of colloids compared with crystal- loids in trauma resuscitation has been highlighted.67 We compared resuscitation with 0.9% saline against HES 130/0.4 with respect to shock reversal, coagulation, gastroin- testinal and renal function in shocked trauma patients pre- senting to a level 1 trauma unit

INTRODUCCIÓN Hidroxyethil starchs HES 130/0,4 Almidón de duración moderada Mínimos efectos sobre la coagulación Tercera generación tetrastarch No estudios clínicos que soporten el uso de este coloide en reanimación en trauma Controversy persists regarding the choice of fluids for resuscitation in critically injured patients. Colloids are advocated as they are associated with rapid attainment of circulatory goals.1 Crystalloids have been recommended since they are cheaper and no survival benefit has been shown for colloids.2 However, resuscitation with large crystalloid volumes has been associated with complications of tissue oedema and an increased incidence of abdominal compartment syndrome.34 The medium molecular weight hydroxyethyl starch, HES 130/0.4, is a moderate duration colloid with minimal effects on coagulation.5 There has been no extensive study of its use in resuscitation of trauma patients. The need for a well-controlled, carefully conducted, prospective, random- ized, double-blind study of colloids compared with crystal- loids in trauma resuscitation has been highlighted.67 We compared resuscitation with 0.9% saline against HES 130/0.4 with respect to shock reversal, coagulation, gastroin- testinal and renal function in shocked trauma patients pre- senting to a level 1 trauma unit

INTRODUCCIÓN Uso de albumina vs para reanimacion en pacientes de UCI y evaluación de sobrevida a 28 días RCT multicentrico Uso de albumina y salina similares desenlaces a 28 días Volumen de salina 1,5 veces mas que albumina 4% It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival. We conducted a multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU.

DESENLACES Primarios Secundarios Días libres de disfunción gastrointestinal a 30 días Score SOFA Duración estancia en UCI Líquidos usados durante cx inicial Tiempo para evaluación de objetivos de reanimación PIA postreanimacion Volumen de líquidos requeridos para lograr objetivos de reanimación en las 24 horas iniciales Tiempo en días hasta la recuperación de la función intestinal determinado por tolerancia la vía oral Volumes of fluids required to meet resuscitation goals over the first 24 hours from study entry 2. Time (days) until recovery of bowel function as determined by tolerance of oral of parenteral feeding Days free of gastrointestinal dysfunction during first 30 days 2. Median and maximal sequential organ failure assessment (SOFA) score 3. Length of stay in Intensive Care Unit (LOS in ICU) 4. Fluid volumes used during initial surgical procedures 5. Time to initial achievement of resuscitation target values 6. Intra-abdominal pressure following resuscitation 7. Time to first passage of stool

MATERIALES Y MÉTODOS CRITERIOS DE INCLUSIÓN Y EXCLUSIÓN

MATERIALES Y MÉTODOS Volumes of fluids required to meet resuscitation goals over the first 24 hours from study entry 2. Time (days) until recovery of bowel function as determined by tolerance of oral of parenteral feeding Days free of gastrointestinal dysfunction during first 30 days 2. Median and maximal sequential organ failure assessment (SOFA) score 3. Length of stay in Intensive Care Unit (LOS in ICU) 4. Fluid volumes used during initial surgical procedures 5. Time to initial achievement of resuscitation target values 6. Intra-abdominal pressure following resuscitation 7. Time to first passage of stool

SCORES ISS Utiliza las siete regiones corporales del AIS 1 (menor) a 6 (fatal) puntos las lesiones ISS 0 a 75 The Injury Severity Score (ISS) is an anatomical scoring system that provides an overall score for patients with multiple injuries. Each injury is assigned an Abbreviated Injury Scale (AIS) score and is allocated to one of six body regions (Head, Face, Chest, Abdomen, Extremities (including Pelvis), External). Only the highest AIS score in each body region is used. The 3 most severely injured body regions have their score squared and added together to produce the ISS score. The ISS score takes values from 0 to 75. If an injury is assigned an AIS of 6 (unsurvivable injury), the ISS score is automatically assigned to 75. The ISS score is virtually the only anatomical scoring system in use and correlates slinearly with mortality, morbidity, hospital stay and other measures of severity. It's weaknesses are that any error in AIS scoring increases the ISS error, many different injury patterns can yield the same ISS score and injuries to different body regions are not weighted. Also, as a full description of patient injuries is not known prior to full investigation & operation, the ISS (along with other anatomical scoring systems) is not useful as a triage tool. Baker SP et al, "The Injury Severity Score: a method for describing patients with multiple injuries and evaluating emergency care", J Trauma 14:187-196;1974

SCORES ISS Utiliza las siete regiones corporales del AIS 1 (menor) a 6 (fatal) puntos las lesiones ISS 0 a 75 The Injury Severity Score (ISS) is an anatomical scoring system that provides an overall score for patients with multiple injuries. Each injury is assigned an Abbreviated Injury Scale (AIS) score and is allocated to one of six body regions (Head, Face, Chest, Abdomen, Extremities (including Pelvis), External). Only the highest AIS score in each body region is used. The 3 most severely injured body regions have their score squared and added together to produce the ISS score. The ISS score takes values from 0 to 75. If an injury is assigned an AIS of 6 (unsurvivable injury), the ISS score is automatically assigned to 75. The ISS score is virtually the only anatomical scoring system in use and correlates slinearly with mortality, morbidity, hospital stay and other measures of severity. It's weaknesses are that any error in AIS scoring increases the ISS error, many different injury patterns can yield the same ISS score and injuries to different body regions are not weighted. Also, as a full description of patient injuries is not known prior to full investigation & operation, the ISS (along with other anatomical scoring systems) is not useful as a triage tool. Baker SP et al, "The Injury Severity Score: a method for describing patients with multiple injuries and evaluating emergency care", J Trauma 14:187-196;1974

SCORES SOFA Sistema de medición diaria de falla orgánica múltiple de seis disfunciones orgánicas Va de 0 (normal) a 4 (el mas anormal) Puntuación de 0 a 24 puntos Volumes of fluids required to meet resuscitation goals over the first 24 hours from study entry 2. Time (days) until recovery of bowel function as determined by tolerance of oral of parenteral feeding El sistema SOFA (Sequential Organ Failure Assessment) se creó en una reunión de consenso de la European Society of Intensive Care Medicine en 1994 y nuevamente revisado en 1996. El SOFA es un sistema de medición diaria de fallo orgánico múltiple de seis disfunciones orgánicas. Cada órgano se clasifica de 0 (normal) a 4 (el más anormal), proporcionando una puntuación diaria de 0 a 24 puntos. El objetivo en el desarrollo del SOFA era crear un score simple, confiable y continuo, y fácilmente obtenido en cada institución. El SOFA durante los primeros días de ingreso en la UCI es un buen indicador de pronóstico. Tanto la media, como el score más alto son predictores particularmente útiles de resultados. Independiente de la puntuación inicial, un aumento en la puntuación SOFA durante las primeras 48 horas en la UCI predice una tasa de mortalidad de al menos el 50%.

ALGORITMO DE INTERVENCIÓN Reanimación completada cuando se alcanzaron los objetivos hemodinámicos y renales y se mantenían Si persistía el sangrado se llevo el paciente a cirugía Resus- citation was deemed complete when haemodynamic and renal targets were achieved and sustained. Patients with clinical evidence of continuing bleeding underwent emer- gency surgery without waiting for full resuscitation. Patients undergoing surgery continued to receive appropriate i.v. fluid resuscitation according to the algorithm

MATERIALES Y MÉTODOS Estudio finalizó al fallecer el paciente o lograrse la recuperación de la función gastrointestinal Seguimiento por 30 días Entrevista personal o telefónica Eventos adversos serios reportados al comité de ética

LECTURA CRITICA Validez Interna Relevancia de los Resultados Validez Externa

DETERMINANTES DE VALIDEZ INTERNA Fueron los pacientes aleatorizados? Aleatorización oculta? Pacientes analizados en el grupo al que se aleatorizaron?

DETERMINANTES DE VALIDEZ INTERNA Los grupos de intervención y control iniciaron con el mismo pronóstico? Pacientes aleatorizados? Aleatorización fue oculta? Fueron los pacientes de los grupos de estudio similares con respecto a los factores pronósticos conocidos?

DETERMINANTES DE VALIDEZ INTERNA Pacientes aleatorizados? Aleatorización fue oculta? Números aleatorios Agrupados en bloques de 8 para cada categoría de trauma en relación 1:1 Liquido preparados en envases idénticos sellados con plástico negro Etiquetado como penetrante y contuso y numeración consecutiva The resuscitation fluids were prepared by sealing identical 500 ml bags in black plastic which concealed the label and contents. Penetrating and blunt trauma were randomized separately and data for the two categories analysed inde- pendently. Randomization was by random numbers grouped in blocks of 8 for each category of trauma in a ratio of 1:1 for the study fluid. Using these numbers, the trial pharmacist pre-packed numbered boxes labelled ‘Blunt’ or ‘Penetrating’ containing blinded study fluid that were then placed sequentially into a warming cabinet in the trauma resuscitation room.

Factores pronósticos conocidos?

DETERMINANTES DE VALIDEZ INTERNA Se mantuvo un equilibrio en el pronóstico conforme progresaba el estudio? Como se mantuvo el cegamiento? Seguimiento adecuado y análisis por intención a tratar?

Como se mantuvo el cegamiento?

Como se mantuvo el cegamiento? PACIENTES E INVESTIGADORES Intervención con liquidas envasados en bolsas negras Preparación por farmaceuta RECOLECCIÓN DE DATOS ANALISIS DE LOS DATOS

Seguimiento adecuado y análisis por intención a tratar? Seguimiento completo? Analizados al grupo que se asignaron? Se detuvo de forma temprana?

LECTURA CRITICA Validez Interna Relevancia de los Resultados Validez Externa

RELEVANCIA DE RESULTADOS

RELEVANCIA DE RESULTADOS Función gastrointestinal No hubo diferencias en la recuperación de la función gastrointestinal entre los grupos Tres pacientes en el grupo P-SAL presentaron síndrome de compartimiento abdominal después de recibir 19, 17 y 13,5 litros respectivamente There was no difference in the recovery of gastrointestinal function between the groups. Similar proportions of surviving patients in both categories and in the two groups within those categories (60%) had recovered gastrointestinal function by day 5. However, three patients in the P-SAL group developed abdominal compartment syndrome after 696 receiving 19, 17, and 13.5 litres, respectively. The first two of these had abdominal injuries and subsequently died. The third had no abdominal injuries but required laparotomy for secondary abdominal compartment syndrome. Coagulation All groups apart from B-HES had near-normal TEG values on enrolment and showed similar mild deterioration in coagu- lation over the resuscitation period. There was little evidence of trauma-induced coagulopathy in this study. Although both HES groups showed some evidence of impaired coagulation on enrolment [decreased maximum amplitude (MA)], there was no evidence of this effect in the SAL groups, where the TEG measures all fell within the normal range. The P-HES showed minor deterioration in the worst TEG measures Hb >0.5 ml kg–1 h –1 Consider cardiac or chest pathology Urine output CVP 500 ml fluid** a Downloaded from http://bja.oxfordjournals.org/ at HINARI Colombia Administrative Account on January 31, 2012

RELEVANCIA DE RESULTADOS Coagulación Solo el grupo B-HES tuvo valores de TEG cerca a la normalidad Al enrolamiento y mostró deterioro en el periodo de reanimación Poca evidencia de coagulopatia inducida por trauma Los grupos HES mostraron Disminución de la MA R-time prolongado No alteraciones de TEG en los grupos de salina There was no difference in the recovery of gastrointestinal function between the groups. Similar proportions of surviving patients in both categories and in the two groups within those categories (60%) had recovered gastrointestinal function by day 5. However, three patients in the P-SAL group developed abdominal compartment syndrome after 696 receiving 19, 17, and 13.5 litres, respectively. The first two of these had abdominal injuries and subsequently died. The third had no abdominal injuries but required laparotomy for secondary abdominal compartment syndrome. Coagulation All groups apart from B-HES had near-normal TEG values on enrolment and showed similar mild deterioration in coagu- lation over the resuscitation period. There was little evidence of trauma-induced coagulopathy in this study. Although both HES groups showed some evidence of impaired coagulation on enrolment [decreased maximum amplitude (MA)], there was no evidence of this effect in the SAL groups, where the TEG measures all fell within the normal range. The P-HES showed minor deterioration in the worst TEG measures Hb >0.5 ml kg–1 h –1 Consider cardiac or chest pathology Urine output CVP 500 ml fluid** a Downloaded from http://bja.oxfordjournals.org/ at HINARI Colombia Administrative Account on January 31, 2012

RELEVANCIA DE RESULTADOS Reanimación FC, TA, PVC respondieron similarmente en todos los grupos No hubo correlación con mejoría en el lactato Algoritmo de reanimación adecuada adherencia ScvO2 no excedió del 60% durante las primeras 4 h de la reanimación Concentraciones de lactato elevadas en el 60% de los pacientes en todos los grupos Excepto B-HES en el cual el 100% tenia elevado el lactato There was no difference in the recovery of gastrointestinal function between the groups. Similar proportions of surviving patients in both categories and in the two groups within those categories (60%) had recovered gastrointestinal function by day 5. However, three patients in the P-SAL group developed abdominal compartment syndrome after 696 receiving 19, 17, and 13.5 litres, respectively. The first two of these had abdominal injuries and subsequently died. The third had no abdominal injuries but required laparotomy for secondary abdominal compartment syndrome. Coagulation All groups apart from B-HES had near-normal TEG values on enrolment and showed similar mild deterioration in coagu- lation over the resuscitation period. There was little evidence of trauma-induced coagulopathy in this study. Although both HES groups showed some evidence of impaired coagulation on enrolment [decreased maximum amplitude (MA)], there was no evidence of this effect in the SAL groups, where the TEG measures all fell within the normal range. The P-HES showed minor deterioration in the worst TEG measures Hb >0.5 ml kg–1 h –1 Consider cardiac or chest pathology Urine output CVP 500 ml fluid** a Downloaded from http://bja.oxfordjournals.org/ at HINARI Colombia Administrative Account on January 31, 2012

RELEVANCIA DE RESULTADOS Lactato There was no difference in the recovery of gastrointestinal function between the groups. Similar proportions of surviving patients in both categories and in the two groups within those categories (60%) had recovered gastrointestinal function by day 5. However, three patients in the P-SAL group developed abdominal compartment syndrome after 696 receiving 19, 17, and 13.5 litres, respectively. The first two of these had abdominal injuries and subsequently died. The third had no abdominal injuries but required laparotomy for secondary abdominal compartment syndrome. Coagulation All groups apart from B-HES had near-normal TEG values on enrolment and showed similar mild deterioration in coagu- lation over the resuscitation period. There was little evidence of trauma-induced coagulopathy in this study. Although both HES groups showed some evidence of impaired coagulation on enrolment [decreased maximum amplitude (MA)], there was no evidence of this effect in the SAL groups, where the TEG measures all fell within the normal range. The P-HES showed minor deterioration in the worst TEG measures Hb >0.5 ml kg–1 h –1 Consider cardiac or chest pathology Urine output CVP 500 ml fluid** a Downloaded from http://bja.oxfordjournals.org/ at HINARI Colombia Administrative Account on January 31, 2012

RELEVANCIA DE RESULTADOS Lactato There was no difference in the recovery of gastrointestinal function between the groups. Similar proportions of surviving patients in both categories and in the two groups within those categories (60%) had recovered gastrointestinal function by day 5. However, three patients in the P-SAL group developed abdominal compartment syndrome after 696 receiving 19, 17, and 13.5 litres, respectively. The first two of these had abdominal injuries and subsequently died. The third had no abdominal injuries but required laparotomy for secondary abdominal compartment syndrome. Coagulation All groups apart from B-HES had near-normal TEG values on enrolment and showed similar mild deterioration in coagu- lation over the resuscitation period. There was little evidence of trauma-induced coagulopathy in this study. Although both HES groups showed some evidence of impaired coagulation on enrolment [decreased maximum amplitude (MA)], there was no evidence of this effect in the SAL groups, where the TEG measures all fell within the normal range. The P-HES showed minor deterioration in the worst TEG measures Hb >0.5 ml kg–1 h –1 Consider cardiac or chest pathology Urine output CVP 500 ml fluid** a Downloaded from http://bja.oxfordjournals.org/ at HINARI Colombia Administrative Account on January 31, 2012

RELEVANCIA DE RESULTADOS Lactato There was no difference in the recovery of gastrointestinal function between the groups. Similar proportions of surviving patients in both categories and in the two groups within those categories (60%) had recovered gastrointestinal function by day 5. However, three patients in the P-SAL group developed abdominal compartment syndrome after 696 receiving 19, 17, and 13.5 litres, respectively. The first two of these had abdominal injuries and subsequently died. The third had no abdominal injuries but required laparotomy for secondary abdominal compartment syndrome. Coagulation All groups apart from B-HES had near-normal TEG values on enrolment and showed similar mild deterioration in coagu- lation over the resuscitation period. There was little evidence of trauma-induced coagulopathy in this study. Although both HES groups showed some evidence of impaired coagulation on enrolment [decreased maximum amplitude (MA)], there was no evidence of this effect in the SAL groups, where the TEG measures all fell within the normal range. The P-HES showed minor deterioration in the worst TEG measures Hb >0.5 ml kg–1 h –1 Consider cardiac or chest pathology Urine output CVP 500 ml fluid** a Downloaded from http://bja.oxfordjournals.org/ at HINARI Colombia Administrative Account on January 31, 2012

DATOS DE LABORATORIO

FUNCIÓN RENAL --- RIFLE

FUNCIÓN RENAL

RELEVANCIA DE LOS RESULTADOS Que tan grande es el efecto del tratamiento? Como se precisa la estimación del efecto del tratamiento?

VALIDEZ EXTERNA Criterios inclusión Criterios exclusión Son similares los pacientes del estudio a los de mi practica clínica? Criterios inclusión Criterios exclusión Trauma contuso o penetrante Requieran mas de 3 litros de volumen en la reanimación Edad entre 18-60 años Edema pulmonar por sobrecarga Alergia al HES Injuria renal conocida, dialisis Hipernatremia o hipercloremia severa al ingreso

VALIDEZ EXTERNA Criterios exclusión Criterios exclusión Son similares los pacientes del estudio a los de mi practica clínica? Criterios exclusión Criterios exclusión TCE severo Sangrado intracraneal severo Lesión severa por aplastamiento No detectar PA después de 2 litros de LEV de bolo Taponamiento cardiaco por clínica Shock neurogenico VIH conocido Admisión > 6 hrs después del trauma Uso de coloides previos en reanimación Otro ensayo o se rehusaron

VALIDEZ EXTERNA Son similares los pacientes del estudio a los de mi practica clínica? Fueron los resultados importantes para el paciente? Es mayor el beneficio que el riesgo y el costo del tratamiento propuesto?

PREGUNTAS Porque los desenlaces primarios no forman parte del titulo? Porque la conclusión se enfoca sobre los desenlaces secundarios en especial depuración de lactato y función renal? Porque usar epinefrina como vasopresor o inotropico ? Si esta incrementa los niveles de lactato

CARTAS AL EDITOR

CARTAS AL EDITOR los pacientes pueden haber muerto antes de que tuvieran la oportunidad de desarrollar lesión renal y esto puede haber sesgado los resultados. The details of recovery of gastrointestinal function on day 5 (the specified end-point) for surviving patients are as follows: P-HES 20/31 (%64.5), P-SAL 17/30 (56.7%), B-HES 11/18 (61.1%), B-SAL 12/20 (60%)

RESPUESTAS Recuperación de la función gastrointestinal Epinefrina P-HES 20/31 (%64.5), P-SAL 17/30 (56.7%), B-HES 11/18 (61.1%), B-SAL 12/20 (60%) Epinefrina P-HES 3/36, P-SAL 3/31, B- HES 2/21, B-SAL 1/22 Lactato P-HES and P-SAL 0.68 lactate units (95% CI: 0.07 to 1.29), p=0.029. The details of recovery of gastrointestinal function on day 5 (the specified end-point) for surviving patients are as follows: P-HES 20/31 (%64.5), P-SAL 17/30 (56.7%), B-HES 11/18 (61.1%), B-SAL 12/20 (60%)

DATOS DE MORTALIDAD P-HES . P-SAL . B-HES . B-SAL . Survived 30 28 14 19 Total deaths 6 3 Early deaths 5 1 2 ICU deaths . Post-ICU deaths . After Exit .

CONCLUSIONES Se requieren 1,5 mas cristaloides para la reanimación en trauma penetrante que tetrastarch P-HES 4,2 L vs P-SAL 7,4 L Este efecto no se nota sobre la normalizacion de la función gastrointestinal No se puede afirmar lo mismo del trauma contuso En términos de los dos brazos del estudio no hay diferencias significativas en los dos desenlaces primarios del estudio P-HES with a positive balance of 4.2L as opposed to a positive balance for P-SAL of 7.4L no differences were found between HES 130/0.4 and 0.9% saline in either of the two primary study endpoints: fluid volume needed during the first 24 hours and number of patients achieving normal gastrointestinal function by day 5. In penetrating trauma, HES 130/0.4 reduced fluid requirement significantly but less than generally expected and showed no effect on normalization of gastrointestinal function

CONCLUSIONES Se requieren estudios con mayor tamaño de muestra para demostrar los beneficios sobre la función renal y depuración de lactato Se requieren mas estudios con alto nivel de evidencia para demostrar los beneficios de la reanimación en trauma con almidones de tercera generación HES 130/0,4 se va posicionando como un coloide seguro con mejoras respecto a sus predecesores. Las cartas al editor son una herramienta que permite ampliar la información de los artículos y cuestionar sus resultados P-HES with a positive balance of 4.2L as opposed to a positive balance for P-SAL of 7.4L no differences were found between HES 130/0.4 and 0.9% saline in either of the two primary study endpoints: fluid volume needed during the first 24 hours and number of patients achieving normal gastrointestinal function by day 5. In penetrating trauma, HES 130/0.4 reduced fluid requirement significantly but less than generally expected and showed no effect on normalization of gastrointestinal function

GRACIAS