Protocolo GQ  Actualización 2005
No hay novedades importantes respecto al manejo general que se contemplaba
en el protocolo anterior.
Evaluación
Dado que los pacientes presentan en numerosas ocasiones lesiones asociadas se
recomienda ante la mínima sospecha realizar TAC helicoidal completo (Cráneo, tórax,
abdomen, pelvis…con contraste si es preciso) al inicio, antes incluso de ingresar en la U
de GQ. (Sheridan 2004).
La monitorización con Swan Ganz es bastante discutible y se investigan otros
métodos (además de los clásicos, PVC, diuresis, FC, etc.) para valorar la eficacia de la
resucitación (como la medida del volumen sanguíneo intratorácico, o la valoración de la
perfusión tisular con espectroscopia por infrarrojos, o la medida directa del O2 tisular).
Debe administrarse toxoide tetánico: 0,5 mL im.
Fluidoterapia: Resucitación 1º día
La fórmula de Parkland /Baxter (4 mL/Kg/BSA/24h) sigue siendo considerada el
“gold standard”, y como tal la más habitualmente utilizada (Sheridan 2002):
Sin embargo diversos artículos, en la mayoría de los cuales se han utilizado
sistemas de monitorización como el Swan-Ganz, señalan necesidades mayores que las
que se derivan de dicha fórmula (hasta 5- 9 mL/Kg/BSA/24h), y no solo en casos en los
que por haber S de inhalación, o quemaduras eléctricas pudieran esperarse unas
necesidades mayores. (Holm 2000). (Cartotto 2002)
Para el cálculo de la SCQ puede utilizarse la regla de los 9 o el diagrama de
Lund & Browder (más adecuado para niños). En www.sagediagram.com puede
encontrarse un progrma informático para un cálculo mas preciso
1
Albúmina
El tema ha seguido siendo controvertido. En la mayoría de las Unidades de mas
prestigio (Shriner, etc.) que atienden a GQ parece que se ha seguido utilizando con
criterios similares a los reseñados previamente (1-2/L/d a partir de las primeras 8 horas).
En el 2004 se ha publicado un estudio (SAFE) en el New England con 7000
pacientes de UCI en el cual los resultados con Salino o Albúmina fueron similares, lo
que aunque no hace indicada la administración de Albúmina si que contradice las
conclusiones del estudio Cochrane de 1998 en que se le atribuía un aumento de la
mortalidad.
Haynes (2003) en un metaanálisis de 69 ensayos randomizados con un total de
4755 pacientes, encuentra 4 ensayos con 197 pacientes con lesión por quemaduras,
observando que el número de complicaciones fue menor en los pacientes con
quemaduras tratados con Albúmina frente a los tratados con cristaloides.
Fluidoterapia 2º día
Continúan utilizándose criterios similares.
Por ejemplo, Namias en Irwin-Rippe, 5ª edición del 2003, utiliza Gl5% en
salino 0,45% a un ritmo de mantenimiento de 1.500 cc/m2 / 24h variando según
diuresis. Inicia Albúmina 5% a las 12-24 horas a 42 cc /h (1 L/d) hasta conseguir una
cifra de Albúmina plasmática >2 mg/dL. No utiliza salino hipertónico porque podría
aumentar la mortalidad y la probabilidad de FRA.
Demling (2002) también utiliza GL 5% en salino 0,45%.
En cuanto al salino hipertónico, los estudios realizados hasta ahora no permiten
recomendarlo. Bunn (Cochrane 2004)
Un déficit de bases de -6 o más en las primeras 24 horas se asocia a una mayor
tasa de complicaciones como el SDRA y el FMO, no directamente relacionado con el
porcentaje de SCQ. (Cartotto, 2003)
2
Nutrición y Metabolismo
N. Enteral:
La EAST (Eastern Association for the Surgery of Trauma, 2001)
estableció unas Guidelines para los pacientes de Traumatología con especial referencia
a los Quemados, que han sido recientemente reformuladas por Jacobs (Sep 2004) en
una extensa Revisión. Recomienda (Nivel II) iniciar la N Enteral en < 18h, no utilizar la
Fórmula de Curreri para GQ>50%, no interrumpir intraoperativamente la N Enteral,
aumentar hasta 2 gr/Kg el aporte proteico, no dar mas de 5 mg/kg/min de Glucosa , y
administrar menos del 30% de las calorías en forma de lípidos. Considera que la
estimación de los requerimientos energéticos 1-2 veces a la semana mediante
calorimetría indirecta puede ser útil, y que la recomendación de utilizar fórmulas
enriquecidas no tiene todavía suficiente soporte. Estas recomendaciones son
similares a las que se señalaban en el protocolo anterior.
En la mayoría de las revisiones se sigue considerando que la N Enteral precoz
es beneficiosa (Hart, Andel, etc.).
Sin embargo Peter (2005) en un metanálisis (30 ensayos RND) encuentra que
no hay diferencia en cuanto a la mortalidad, y que aunque la incidencia de
complicaciones parece menor con N. Enteral, ello debe interpretarse con cierta
prevención.
Peck (2004) en un estudio con 27 pacientes no encuentra ninguna ventaja a
iniciar precozmente la N Enteral, vs iniciarla al de 1 semana. Gottschlich en un estudio
con 77 pacientes tampoco encuentra ninguna ventaja. Tampoco otros autores como
Noordenbos. (J Trauma. 2000;49:667–671).
Glutamina
En el estudio de Ye-Ping (30 niños, 2004) la Glutamina disminuyó la alteración
de la permeabilidad intestinal y los niveles de antitoxina, reduciendo el tiempo de
curación de la herida, el coste y el tiempo de estancia. Peng en un estudio con 48
pacientes encuentra que la Glutamina disminuye la lesión intestinal.
Garrel (2003) de Montreal en un estudio con 45 GQ encuentra que la glutamina
reduce la bacteriemia, incluido la provocada por pseudomona, y parece disminuir la
mortalidad. Wyncoll (2001) también apoya el uso de inmunonutrición en general.
En contraste, los del Shriner de Galveston (Hart, Herndon 2003) utilizan una
dieta elemental (Vivonex) y tienen la mortalidad menor del mundo en niños quemados.
Andel en una extensa revisión (Andel 2003) considera que la suplementación con
aminoácidos especiales como la Glutamina o la Arginina, los ω-3, o la vit C ó E no han
demostrado con nivel suficiente de evidencia su eficacia. (Tampoco otras medidas para
modular la respuesta metabólica, como el propranolol, hormonas, etc)
Micronutrientes: (Prelack. 2001)
Puede haber una pérdida progresiva de elementos como el Zinc o el cobre. Se
recomienda suplementar con 25-50 mg/d de Zinc las dietas estándar (Sheridan 2003) y
5 mg día de Cobre. No se recomienda suplementar Hierro (las transfusiones, casi
ineludibles en los GQ, ya lo suplementan). Las dietas enterales suelen contener
3
cantidades incrementadas de Selenio: se recomienda un suplemento de unos 60-190
μgr/d. No se recomiendan suplementos adicionales de vitamina A, aparte de lo que se
pueda administrar en los multivitamínicos habitualmente empleados (En el Cecil se
recomiendan 10-25.000 U/d). Vitaminas B se dan a dosis altas (x 5-10).
Vitamina C
En el Rippe (2003), Namias dice que la Vit C disminuye el volumen requerido
para la resucitación, disminuye la formación de edema, mejora la oxigenación y
disminuye el nº de días de Ventilación. Mecánica, según el ensayo de Tanaka (ya
reseñado en el protocolo previo). Da Vit C iv a 66 mg/Kg/h durante las primeras 24
horas.
En el Cecil (2004) se recomienda dar al menos 1 gr/d.
Sheridan (2004) reseña que numerosos estudios han demostrado que con la
administración precoz de vitamina C se disminuye el volumen necesario para la
resucitación, pero estima que todavía no se puede considerar un estándar de la
resucitación del GQ. Protegería del daño microvascular epitelial que se produciría
inmediatamente tras la quemadura. Las necesidades habituales son de unos 200 mg/d y
las soluciones de Nutrición suelen tener 80 a 340 mg/L. Otras vitaminas (B, E, K etc no
tiene recomendación específica en GQ, siguiéndose las pautas habituales en paciente
crítico).
Propranolol
En estudios realizados sobretodo en niños, parece que además de reducir la FC,
frena el gasto calórico mejorando la síntesis proteica muscular. También parece que
reduce la acumulación de grasa en el Hígado que se suele asociar a la sepsis. Sin
embargo esta reducción en el catabolismo no parece haberse asociado a una clara
influencia en la mortalidad.
Algunos apuntan la posibilidad de administrarlo para reducir la respuesta
hipermetabólica, durante varias semanas, guiándose por la reducción de la Frecuencia
cardiaca en un 20%. Tierney 2005
Hormonas: (growth hormone, insulin, insulin-like growth factor 1, oxandrolone, and testosterone,
estradiol, TGF-α y β… ),:
Los de los centros Shriner (Herndon, etc) son los que mas han estudiado este
tema. En general los estudios han mostrado mejoría en los parámetros metabólicos pero
no hay resultados concluyentes en cuanto a la evolución, mortalidad, etc que permitan
recomendarlos con carácter general.
La excepción podría ser la Insulina en cuanto a que el control estricto de
glucemia se ha asociado en estudios de alto nivel como un factor que,
independientemente de la patología de base mejora la supervivencia del paciente crítico.
4
QUEMADURAS ELÉCTRICAS
Una buena revisión puede encontrarse en Practice of Emergency Medicine,
Harwood-Nuss Sosnow (2001). Y en las revisiones generales que se detallan en la
bibliografía (Cecil,…).
La intensidad de la corriente (Amperaje) depende del voltaje y de la Resistencia
(A=Voltaje/Resistencia) (resistencia en orden descendente: hueso, tejido adiposo,
tendón, piel, músculo, sangre, nervio). El camino que sigue la descarga puede
condicionar la lesión (si atraviesa el cerebro o el corazón puede producir la muerte
instantáneamente. El tipo de corriente es también importante. La corriente alterna
doméstica es en principio peor que la corriente continua.
La destrucción muscular suele ser mayor de lo que parece por afectar a zonas
profundas (en mayor contacto con el hueso, que ofrece más resistencia al paso de la
corriente). Es un error frecuente minimizar el alcance de las lesiones, lo que puede
conducir a S compartimental no aparente y terminar en amputaciones. Por eso se
recomiendan las Fasciotomía.
Se produce mioglobinuria y Hemoglobinuria como consecuencia de la
destrucción muscular y de Hematíes: Rabdomiolisis + FRA. Hiperpotasemia. Pruitt en
el Cecil (cap 147) recomienda dar 25 g de Manitol iv + 12.5 g en cada Litro de
fluidoterapia, hasta que los pigmentos desaparezcan de la orina.
Se deben investigar fracturas (RX) (por espasmo o convulsión), incluso
vertebrales, y estar atento a la aparición de S compartimental, para cuyo diagnostico
puede ser útil el ECO Doppler para valorar la ausencia de pulso.
También se pueden producir alteraciones en los órganos del aparato digestivo.
Se debe prestar especial atención al ECG. Aunque la CK suele estar elevada
raramente hay IAM.
Se debe forzar la diuresis a 2-3 veces su volumen habitual (100-200 cc/h) y
alcalinizar. Tras reposición hídrica adecuada (mayor que la habitual en GQ puede ser
aconsejable administrar Manitol en caso de rabdomiolisis.
Lesión por rayo: Dura 1/100 a1/1000 sg, pero con un voltaje de 1.000 millones
de voltios y una intensidad de12,000 a 200,000 A. Produce coma, PCR, alteraciones
neurológicas (keraunoparalisis)…
5
COMPLICACIONES
Infección.
Una reciente actualización puede encontrarse en Weber 2004.
La escisión precoz es recomendable (Barret . Hart. 2003). Reduce la
colonización bacteriana y la evolución infecciosa atenuando el catabolismo muscular.
En la primera semana la superficie quemada es típicamente colonizada por Gram
+ (incluyendo MRSA, Enterococos, Streptococcus A beta-hemolítico, y SFCN). Hacia
la 2ª semana aparecen los Gram -, y más tarde los hongos (Cándida, Aspergillus,
Rhizopus…). La infección local se caracteriza por eritema, edema, celulitis, drenaje
purulento, necrosis, fiebre, leucocitosis,…
Las bacteriemias son mucho mas frecuentes conforme aumenta la SC quemada
(55/60 pacientes del Shriner de Boston con >30% de SCQ, tuvieron bacteriemia).
La posibilidad de infección cruzada es muy alta, lo que ha llevado a centros
como el citado a limitar lo más posible la utilización de equipamientos comunes, como
los de hidroterapia (bañera) en GQ. Sin olvidar, naturalmente, las medidas de
aislamiento (guantes, mascarillas, etc) y equipamiento único para cada paciente.
Antibióticos
El volumen de distribución está aumentado en los GQ, por lo que se pueden
necesitar dosis más altas, lo que hace imprescindible la monitorización de niveles.
No está demostrada la eficacia de la administración de Aminoglucósidos en
dosis única en GQ.
Las superficies quemadas están siempre colonizadas hasta que son
definitivamente cubiertas. La administración de antibióticos para tratar de eliminar esa
colonización no solo no la elimina sino que favorece la aparición de gérmenes más
resistentes. Los antibióticos deben administrarse para infecciones definidas
(Bacteriemia, Infección urinaria, Neumonía, Infección de catéter, etc). Con más de 105
Colonias se suele recomendar tratar.
La fiebre per se no es indicación de ttº antibiótico en los GQ, que la presentan
frecuentemente como parte del SIRS, sin que necesariamente haya infección.
La profilaxis se utiliza solo en periodo perioperatorio, inmediatamente antes del
procedimiento y en las 24 horas siguientes.
La proteína C activada se ha utilizado en casos aislados con Sepsis según sus
criterios habituales de utilización.
Tratamiento tópico
6
La sustancia mas utilizada es la Sulfadiazina argéntica (Sivederma,
Flamacine) (puede dar leucopenia transitoria), el Nitrato de plata al 0.5% (se usa poco:
produce alteraciones electrolíticas e hipotermia), y la crema Acetato de Mafenida
(Sulfamylon) 11,1% o mejor 5% (muy eficaz frente a Pseudomonas, aunque también es
un potente inhibidor de la anhidrasa carbónica e induce acidosis metabólica por pérdida
renal de CO3H, lo que dificulta su uso en pacientes en VM con hipercapnia permisiva, y
además podría favorecer el crecimiento de hongos, y su aplicación puede ser dolorosa).
Los ungüentos con Bacitracina se utilizan solo en áreas muy limitadas (p.ej la cara,
donde la Silvederma puede dar alteraciones cosméticas: pigmentación) porque se
absorbe sistémicamente y puede dar nefrotoxicidad. Biobrane.
 No se suelen utilizar para tratamiento de las quemaduras en GQ:
. La Nitrofurazona al 0'2% (Furacin): Es bacteriostático y favorece la
cicatrización. Puede agravar una insuficiencia renal y producir hiperazoemia.
. La Povidona yodada al 10% (Betadine): Es activo frente a gram positivos,
gram negativos y hongos. Produce dolor al ser aplicado y excesiva desecación de las
escaras.
S. INHALACIÓN
-
Factores que contribuyen: 1)Edema de vías respiratorias por efecto directo del
calor y la alteración de la permeabilidad, 2) Broncoespasmo por inhalación de
sustancias irritantes aerosolizadas.3) Oclusión de pequeña vía aérea por deshechos
endobronquiales y alteración del mecanismo ciliar de depuración. 4) Aumento del
espacio muerto y shunt por ocupación alveolar. 5) Disminución de la compliance
por el edema alveolo intersticial y el edema de la pared torácica, 6) Infección
traqueo bronquial o pulmonar. Es esencial mantener in alto índice de sospecha ya
que el mayor error es no diagnosticarlo a tiempo, lo que puede conllevar la
imposibilidad de intubación. La Rx tiende a minimizar el daño. Los
broncodilatadores son útiles.
-
Ventilación mecánica: Son válidas las recomendaciones generales del SDRA:
Volumen tidal bajo: 6-9 ml/Kg, procurando evitar P pico > 40 cmH2O y FiO2>60%.
El decúbito prono, diversas técnicas complejas de ventilación, ECMO, etc se
utilizan raramente o según criterios generales de cada centro. Es recomendable la
intubación precoz en caso de quemaduras profundas de cuello-cara, alteración de
conciencia , S. de inhalación, o ante la sospecha de edema laríngeo. Se ha ensayado,
parece que con buenos resultados iniciales la High-frequency percussive ventilation
(HFPV).
-
la Heparina nebulizada (Desai, 1998: 5000 unidades de Heparina y 3 ml de
acetilcisteina al 20% aerosolizada cada 4 horas durante la primera semana) parecía
prometedora, pero su uso es raramente citado en las revisiones actuales, y en dos
7
estudios recientes en animales no se ha mostrado suficientemente eficaz. (Tasaki,
2002) (ver Editorial de Sheridan).
-
Oxido Nítrico: Mussgrove (2001) estudia 10 pacientes GQ y considera que el NO
es útil sobretodo en el SDRA relacionado con S de Inhalación y no tanto en el
SDRA secundario a SIRS.
Sheridan del MGH en el caso del NEJM de Feb/04, lo utiliza a 20 ppm.
Ichinose - Zapol en un artículo en Circulation/04 dice que dos ensayos (en un solo
centro cada uno), y tres multicéntricos randomizados no han demostrado que
mejore la mortalidad ni la duración de la Ventilación mecánica, por lo que cuestiona
su utilidad real. Si que parecen mejorar determinados parámetros gasométricos,
presiones, etc.
(Mas bibliografía al final).
-
Se investigan otras medidas (la mayor parte en fase de experimentación animal): el
Ketorolac (se ha visto que atenúa los cambios micro vasculares en ovejas), t-PA
(Enkhbaatar, 2004), ATT, Surfactante, la Ventilación líquida, el Dimetil sulfóxido
(ovejas), los inhibidores de la Oxido Nítrico-sintetasa o la ADP ribose-sintetasa,
superoxido dismutasa, etc
Intoxicación por CO asociada a GQ
El CO tiene una afinidad por la Hgb 200 veces mayor que el O2. Desplaza a la
izquierda la curva de disociación de la Hgb. El pulsoxímetro puede mostrar Sat
normales de O2.
Unos niveles de carboxihemoglobina por encima de 1-2% en no fumadores o 45% en fumadores es sospechoso (>5-10% respectivamente es diagnóstico). La vida
media es de unos 320 minutos (80 minutos si se respira O2 100%, y 23 minutos en
Oxigenación hiperbárica a 3 atmósferas) por lo que unos niveles normales transcurridas
una horas no lo excluye. Los pacientes pueden tener una PaO2 normal, con una Sat v O2
baja y acidosis metabólica. La exploración neurológica está alterada en intoxicación
severa. La TAC y la RMN suelen mostrar alteraciones (típicamente en el globus
pallidus). (Abelsohn, 2002)
Es recomendable administrar O2 al 100% durante las primeras horas, ante la
mínima sospecha en GQ.
Respirando aire ambiente el CO se elimina en 250 minutos, con O2 al 100% en
40-60 minutos, y en 30 minutos con O2 a 3 atmósferas.
Ha habido dos ensayos recientes con Oxigenoterapia hiperbárica con resultados
contrarios, pero en cualquier caso su aplicación en GQ presenta enormes dificultades.
El grupo Cochrane (2004) no encuentra criterio suficiente para recomendar su uso.
8
Intoxicación por cianidas
Es frecuente que se produzca gas cianuro y similares en los incendios, como
consecuencia de la combustión de diversos materiales (poliuretano, nylon, acrílicos,
resinas, papel etc). El cianuro se liga de forma reversible con la citocromo oxidasa
inhibiendo la fosforilización oxidativa a nivel mitocondrial. Los niveles de cianidas
suelen estar elevados en los pacientes que provienen de incendios en lugares cerrados y
suelen guardar correlación con los niveles de carboxihemoglobina. Cuando la
determinación de cianuro en sangre oscila entre 0.5 y 1 μgr /ml la clínica suele ser leve,
entre 1 y 3 mgr/L aparece un cuadro grave con alteraciones neurológicas graves y
cuando supera los 3 μgr /ml se supera la dosis letal. Pero su determinación raramente es
posible hacerla con la urgencia necesaria, por lo que habitualmente el tratamiento se
establece en base a la sospecha.
Los síntomas pueden ser poco llamativos (cefalea, mareos taquicardia, etc y
luego letargia, convulsiones y fallo respiratorio. Debe sospecharse en presencia de CO
>15%, acidosis metabólica, y Satv O2 elevada. Esto junto con las circunstancias del
incendio (sitio cerrado, duración de la exposición, etc) deben llevar a la sospecha.
El tratamiento clásico eran los nitratos que inducen la formación de meta-Hgb.
El cianuro tiene mayor afinidad por la meta-Hgb, que por la citocromo oxidasa.
 Kit con: Nitrito de Amilo inhalado seguido de Nitrato Sódico por vía iv al
3%, 0.9 mgr/Kg./gr de hemoglobina, hasta una dosis máxima de 300-450 mgr, a una
velocidad de 2-5 ml/min. En caso de no producirse respuesta repetir el pratamiento tras
30 minutos pero con la mitad de dosis. Con ello se consiguen niveles de
metahemoglobinemia del 20-30%, los cuales deben ser monitorizados para mantenerlos
por debajo del 40%.
Tras los nitratos se administraba Tiosulfato Sódico como dador de grupos sulfuros que
faciliten la conversión del cianuro en tiocianato a nivel hepático. El tiocianato es poco
tóxico y se elimina rápidamente por la orina. La dosis a infundir vía intravenosa es de
12.5 gr de solución al 25%, es decir, 50 ml.
Sin embargo hay que tener en cuenta que los Nitratos producen hipotensión, la
metahemoglobina incrementa la hipoxemia al competir con la hemoglobina por el O2, y
el tiocianato a concentraciones altas también puede ser tóxico.
Hoy en día se utiliza preferentemente la Hidroxicobalamina (Cyanokit): B12
Mayor afinidad con el cianuro que la citocromo oxidasa. Al unirse con el cianuro se
forma cianocobalamina que es eliminada vía renal. La ventaja de esta sobre los nitratos
es que carece de efectos adversos, no produce meta-Hgb-emia ni hipotensión, por lo que
puede administrarse de forma segura en pacientes críticos. Sauer(2001)
Cyanokit : es medicamento extranjero. Cuesta 416 €. Viene en frasco de 2,5 gr
para reconstituir con 100 mL de Salino. En intoxicación por cianuro se utiliza a dosis de
5 gr (2 frascos) en 30 minutos, que puede repetirse en administración algo mas lenta (2
horas). No debe darse conjuntamente Tiocianato porque disminuye su eficacia.
Produce una pigmentación rosada reversible de piel y mucosas, y orina rojiza.
(También se utiliza en intoxicación por NTP a 25 mg/h).
9
Síndrome compartimental abdominal
Es una complicación del GQ a la que recientemente se ha prestado más atención.
El aumento de Presión Intraabdominal incrementa las presiones inspiratorias y los
requerimientos de fluidoterapia. Es más, solo el 40% de los pacientes con aumento
importante de la P intraabdominal sobreviven. El diagnóstico puede hacerse midiendo la
presión en la vejiga urinaria: si esta es > 30 mm Hg indica alto riesgo. Tierney 2005
Hobson (2002). Lo encuentra en 10 de 1040 pacientes. Describe como medir la P
intraabdominal y hacer la descompresión.
Trombosis venosa profunda
La necesidad de profilaxis antitrombótica en GQ es controvertida. (Saffle 2003)
Según un reciente estudio de Wibbenmeyer (2003)la prevalencia de
tromboembolismo en los quemados es moderada/alta, por lo que la recomendación de
profilaxis resulta adecuada.
Saliba (2001) hace una extensa revisión de otros usos de la Heparina en GQ.
Hipoadrenalismo
Es una complicación no muy frecuente en GQ pero muy grave. La presentan sobretodo
pacientes ancianos que han estado mas de dos semanas en UCI que permanecen
dependientes de vasopresores, con alteraciones electrolíticas no explicables, con
fiebre… Se investigará el cortisol plasmático tratando con corticoides su posible
déficit.
10
Bibliografía.-
► Revisiones
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Sheridan, What is new in burns and metabolism?.J Am Coll Surg.198:;2: 243-264. 2004.
Revisión extensa que aborda practicamente todos los apartados. Sheridan (volver)
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253-267
Patterson. Pain Mangement. Burns 30: A10-A15. 2004.
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2004
Oliver. Burns. Resuscitation and early managemet. E-Medicine.
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Doherty. Chapter 15. Burns & Other Thermal Injuries. 2002. (volver)
Pruitt. Cecil 22ª Ed. 2004 . Cecil (volver)
Heimbach, What is new in burns and metabolism?.J Am Coll Surg.194:;2: 156-165. 2002.
Sheridan, Burns. Crit Care Med 30 11 Suppl (2002), pp. S500–S514. Sheridan. (volver)
Pigmented urine is commonly seen in the setting of high-voltage or very deep thermal injury. To avoid
renal tubular injury, pigment should be cleared promptly. This can usually be done in 2–3 hrs by
administration of additional crystalloid to the end point of a urine output of 2 mL·kg-1·hr-1. Judicious
administration of bicarbonate may facilitate clearance of myoglobin by preventing its entry into the
11
tubular cells. In rare circumstances, mannitol is a reasonable adjunct, but its use obscures urine output as
an indicator of circulating volume, and central venous pressures should be monitored
After the capillary leak seals and fluid infusions are reduced, wound management has an increasing
influence on the amount of fluid and type of electrolyte replacement required. Wounds treated with
nonaqueous topicals (such as silver sulfadiazine) generate a free-water requirement, generally provided as
5% dextrose in water or free water added to enteral feedings. Extreme hypernatremia can be associated
with adverse central nervous system effects, including intracranial bleeding. Wounds treated with
aqueous topical agents (such as 5% silver nitrate solution) are associated with electrolyte leeching and
secondary hyponatremia that requires isotonic crystalloid and additional salt in enteral feedings. Cerebral
edema and seizures can occur with severe hyponatremia (). Overly rapid correction of hyponatremia may
result in central pontine demyelinating lesions). There is serious morbidity associated with poor control of
serum sodium at this time, and it should be monitored and kept in the physiologic range. Serum ionized
calcium and magnesium should be monitored as supplementation is commonly required during this
period.
The clinical consequences of inhalation injury include upper airway edema from direct thermal injury
exacerbated by systemic capillary leak, bronchospasm from aerosolized irritants, small airway occlusion
from sloughed endobronchial debris and loss of the ciliary clearance mechanism, increased dead space
and intrapulmonary shunting from alveolar flooding, decreased lung and chest wall compliance from
interstitial and alveolar edema and swelling or burn of the chest wall, and infection of the denuded
tracheobronchial tree (tracheobronchitis) or pulmonary parenchyma (pneumonia).
Management is supportive only. Upper airway edema usually resolves in 2 to 3 days and can be
facilitated by elevation of the head of the bed and avoidance of excessive fluid administration.
Bronchospasm generahly responds to inhaled [beta]-agonists. If mechanical ventilation is required, air
trapping should be anticipated and managed by ensuring adequate expiratory times and being alert for
dynamic hyperinflation (). Inflating pressures to >40 cm H 2O should be avoided, unless there is severely
impaired chest wall compliance, implying that the inflating pressures are not transpleural. Children with
even severe inhalation injury typically have normal gas exchange and compliance for 48–72 hrs after
injury. During this period, it is ideal to effect interhospital transfers or needed operations, as deteriorating
gas exchange may complicate both.
In the days after inhalation injury, endobronchial debris collect, alveolar segments flood, compliance
suffers, infection occurs, and gas exchange deteriorates. This is managed with vigorous pulmonary toilet
and ventilator support designed to prevent secondary lung injury by capping inflating pressures at 40 cm
H2O and concentrations of oxygen at 60% if possible. Both have been demonstrated to cause pulmonary
injury (). The end points of oxygenation and ventilation should be reset to physiologically acceptable
ventilation (any Paco2 with a pH of >7.2) and oxygenation (any Pao 2 consistent with an Sao2 of >90%).
This approach, permissive hypercapnia, is associated with excellent outcomes). If the reset physiologic
end points cannot be achieved without violating pressure and oxygen caps for significant lengths of time,
innovative methods of support such as inhaled nitric oxide), high-frequency percussive ventilation (), or
extracorporeal life support () should be considered, or these caps will be transiently violated
Sheridan, Comprehensive Treatment of Burns. Curents problems in Surgery.
Sept 2001. (Monografía)
Sheridan . Surgery: Scientific Principles & Practice. Editor(s): Greenfield, 3rd Edition © 2001. Chapter
12. Lippincott Williams & Wilkins
Yowler. Recent advances in Burn Care. Current opinion in Anesthesiology. 14:251-255. 2001.
Cioffi, What is new in burns and metabolism?.J Am Coll Surg.192:;2: 241-255. 2001.
12
► Fluidoterapia.
Bunn. Hypertonic versus near isotonic crystalloid for fluid resuscitation in critically ill patients.
[Systematic Review] Cochrane Database of Systematic Reviews. 4, 2004. Cochrane. (volver)
Main results: Fourteen trials with a total of 956 participants are included in the meta-analysis. The pooled
relative risk (RR) for death in trauma patients was 0.84 (95% confidence interval [CI] 0.69-1.04); in
patients with burns 1.49 (95% CI 0.56-3.95); and in patients undergoing surgery 0.51 (95% CI 0.09,
2.73). In the one trial that gave data on disability using the Glasgow outcome scale, the relative risk for a
poor outcome was 1.00 (95% CI 0.82, 1.22).
Conclusions: This review does not give us enough data to be able to say whether hypertonic crystalloid
is better than isotonic and near isotonic crystalloid for the resuscitation of patients with trauma, burns,
or those undergoing surgery. However, the confidence intervals are wide and do not exclude clinically
significant differences. Further trials which clearly state the type and amount of fluid used and that are
large enough to detect a clinically important difference are needed.
Cartotto , Toronto Canada.A prospective study on the implications of a base deficit during fluid
resuscitation. J Burn Care Rehabil. 2003 Mar-Apr;24(2):75-84. Cartotto. (volver)
An excessive base deficit (BD) and elevated serum lactate are increasingly recognized as important
markers of a malperfusion state during the resuscitation of thermally injured patients. In a previous
retrospective study, we found that patients with a BD less than -6 mmol/l during fluid resuscitation
developed more severe systemic inflammatory response syndrome (SIRS), more frequent acute
respiratory distress syndrome (ARDS), and more severe multiple organ dysfunction syndrome (MODS).
The object of this study was to reexamine prospectively the relationship between the BD during fluid
resuscitation and the subsequent development of SIRS, ARDS, and MODS by undertaking a prospective
observational study of a cohort of consecutive burn patients. Analysis was completed on 38 patients with
a mean age of 39 +/- 17 years and a mean %TBSA burn of 36 +/- 15%. The mean BD in the first 24 hours
was less than -6 mmol/l in five patients (BD24 < -6 group), and was greater than -6 mmol/L in 33 patients
(BD24 > -6 group). Patients in both groups were resuscitated to nearly identical endpoints of urinary
output (1.2 ml/kg/hr in the BD24 < -6 group vs 1.3 ml/kg/hr in the BD24 > -6 group). Patients in the
BD24 < -6 group had a trend toward a greater number of SIRS signs on the first postburn day, had a
significantly higher incidence of ARDS (P =.02), and had significantly more severe MODS (P <.001)
than patients in the BD24 > -6 group. The results concur with those of our previous retrospective study.
Despite resuscitation to an acceptable urinary output, some burn patients develop a more extreme BD and
go on to experience more severe organ dysfunction than do patients who do not generate a BD. The effect
of specific correction of the BD during fluid resuscitation is not known at this time.
Cartotto, .How Well Does The Parkland Formula Estimate Actual Fluid Resuscitation Volumes. Journal
of Burn Care & Rehabilitation. 23(4):258-265, July/August 2002. (6.7 +/- 2.8 ml/kg/%TBSA) . Cartotto
(volver)
We had anecdotally observed that fluid resuscitation volumes often exceed those estimated by the
Parkland Formula in adults with isolated cutaneous burns. The purpose of this study was to compare
estimated and actual fluid resuscitation volumes using the Parkland Formula. We performed a
retrospective study of fluid resuscitation in patients with burns >= 15% TBSA. Patients with inhalation
injury, high voltage electrical injury, delayed resuscitation, or associated trauma were excluded. We
studied 31 patients (mean age 51 ± 20 years, mean TBSA burn 27 ± 10%). The 24 hour resuscitation
volume of 13 354 ± 7386 ml (6.7 ± 2.8 ml/kg/%TBSA) was significantly greater than predicted (P =
0.001) and exceeded estimated volume in 84% of the patients. The mean urine output in the first 24 hrs
was 1.2 ± 0.6 ml/kg/hr. After the first 8 hours of resuscitation, the infusion rate decreased by 34% in 16
patients (DCR group), while in 15 patients the rate increased by 47% (INCR group). Both the DCR and
INCR groups received significantly more fluid than predicted, (5.6 ± 2.1 ml/kg/%TBSA and 7.7 ± 3.1
ml/kg/%TBSA respectively). The INCR patients had significantly larger full thickness burns (14 ± 11%
vs 3 ± 6%, P < 0.001). Our findings reveal that despite its effectiveness, the Parkland Formula
underestimated the volume requirements in most adults with isolated cutaneous burns, and especially in
those with large full thickness burns.
Holm. Munich .Resuscitation in shock associated with burns. Tradition or evidence-based medicine?.
Resuscitation. 2000 May;44(3):157-64. Holm. (volver)
OBJECTIVE: To summarize the present standards and guidelines for fluid treatment of shock associated
with burns, and to evaluate their scientific support in the literature. DESIGN: Nonsystematic, critical
13
review of the literature regarding the indications for crystalloid and colloid fluid treatment, invasive
monitoring and the use of resuscitation end points in shock associatad with burns. SUMMARY POINTS:
Crystalloid fluid resuscitation of patients with burns is traditionally managed using empirical resuscitation
formulae, with the efficacy monitored by vital signs and urinary output The value of these end points has
been questioned by recent studies, which have suggested that such noninvasive parameters may be
inadequate for detecting malperfusion. No consensus exists regarding appropriate assessment of adequate
resuscitation, and the impact on survival of invasive measures has still to be proven in controlled
randomized trials. Generally, a significantly higher fluid requirement has been demonstrated when
resuscitation is based on invasive cardiorespiratory monitoring. Colloid resuscitation in burns patients is
controversial. Published reports suggest that colloid infusion should be started between 6 and 36 h
following thermal injury. A recent meta-analysis highlighted the shortcomings of albumin in patients with
burns, and this, together with restrictions for the use of plasma products, has obscured the choice of
colloid solution. The effect of colloid resuscitation on survival remains to be proven in burned patients.
CONCLUSION: The current standards for monitoring fluid therapy in patients with large burns are not
supported by scientific data. Further randomized, controlled trials are indicated, and should help establish
general guidelines regarding monitoring and treatment end points in these patients
9.- Schiller, Hyperdynamic resuscitation improves survival in patients with life threatening burns. J. Burn Care
Rehabil. 18 (1997), pp. 10–16
15.- Barton, Resuscitation of thermally injured patients with oxygen criteria as goals of therapy. J. Burn Care
Rehabil. 18 (1997), pp. 1–9.
18. -Holm. Intrathoracic blood volume as endpoint for burn shock resuscitation: An observational study of 24
patients. J Trauma 2000
Kemalyan. The Baxter formula in 1995. Presented at the 28th Annual Meeting of the American Burn Association,
14–17 March 1996, Nashville, TN.
Murphy, , Morbidity associated with resuscitation in excess of predicted volumes. Proc. Am. Burn
Assoc. 19 (1998), p. S200
Huang: Hypertonic sodium resuscitation is associated with renal failure and death. Ann Surg
221(5):543–54; discussion 554–557, 1995
14
► Albúmina
SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive
care unit. N Engl J Med 2004;350:2247-2256. SAFE. (volver)
We randomly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or
normal saline for intravascular-fluid resuscitation during the next 28 days. The primary oupcome measure
was death from any cause during the 28-day period after randomization.
Results Of the 6997 patients who underwent randomization, 3497 were assigned to receive albumin and
3500 to receive saline; the two groups had similar baseline characteristics. There were 726 deaths in the
albumin group, as compared with 729 deaths in the saline group (relative risk of death, 0.99; 95 percent
confidence interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single-organ and multipleorgan failure was similar in the two groups (P=0.85). There were no significant differences between the
groups in the mean (±SD) numbers of days spent in the ICU (6.5±6.6 in the albumin group and 6.2±6.2 in
the saline group, P=0.44), days spent in the hospital (15.3±9.6 and 15.6±9.6, respectively; P=0.30), days
of mechanical ventilation (4.5±6.1 and 4.3±5.7, respectively; P=0.74), or days of renal-replacement
therapy (0.5±2.3 and 0.4±2.0, respectively; P=0.41).
Conclusions In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation
results in similar outcomes at 28 days
Haynes. Albumin administration—what is the evidence of clinical benefit? A systematic review of
randomized controlled trials. Eur J Anaesthesiol 2003;20:771–93. Haynes. (volver)
Results: Seventy-nine randomized trials with a total of 4755 patients were included. No significant
treatment effects were detectable in 20/79 (25%) trials. In cardiac surgery, albumin administration
resulted in lower fluid requirements, higher colloid oncotic pressure, reduced pulmonary oedema with
respiratory impairment and greater haemodilution compared with crystalloid and hydroxyethylstarch
increased postoperative bleeding. In non-cardiac surgery, fluid requirements, and pulmonary and
intestinal oedema were decreased by albumin compared with crystalloid. In hypoalbuminaemia, higher
doses of albumin reduced morbidity. In ascites, albumin reduced haemodynamic derangements, morbidity
and length of stay and improved survival after spontaneous bacterial peritonitis. In sepsis, albumin
decreased pulmonary oedema and respiratory dysfunction compared with crystalloid, while
hydroxyethylstarch induced abnormalities of haemostasis. Complications were lowered by albumin
compared with crystalloid in burn patients. Albumin-containing therapeutic regimens improved
outcomes after brain injury.
Conclusions: Albumin can bestow benefit in diverse clinical settings. Further trials are warranted to
delineate optimal fluid regimens, in particular indications
Horsey . The Cochrane 1998 Albumin Review—not all it was cracked up to be. Eur J Anaesthesiol
2002;19:701–704
Judkins, Burns resuscitation: what place albumin?. Hosp Med 61 (2000), pp. 116–119.
The Cochrane analysis of the use of albumin in critical illness has highlighted the need for more wellconducted studies on colloid use in burns. The lack of objectivity in the press regarding this material has
compromised our ability to deliver those studies. The analysis provides no evidence that albumin is
unsafe for the initial resuscitation of uncomplicated burns, and the fall in its use is more likely to be costrelated.
15
► Nutrición
Peter. A metaanalysis of treatment outcomes of early enteral versus early parenteral nutrition in
hospitalized patients *. Critical Care Medicine. 33(1):213-220, January 2005. Peter (volver)
Design: The authors conducted a metaanalysis of randomized, controlled trials (RCT) comparing early
EN with PN. Studies on immunonutrition were excluded. Measurements and Main Results: Thirty RCTs
(ten medical, 11 surgical, and nine trauma) compared early EN with PN. There was no differential
treatment effect of nutrition type on hospital mortality for all patients (0.6%, p = .4) and subgroups. PN
was associated with increases in infective complications (7.9%, p = .001), catheter-related blood stream
infections (3.5%, p = .003), noninfective complications (4.9%, p = .04), and hospital LOS (1.2 days, p =
.004). There was no effect of nutrition type on technical complications (4.1%, p = .2). EN was associated
with a significant increase in diarrheal episodes (8.7%, p = .001). Publication bias was not demonstrated.
Metaanalytic regression analysis did not demonstrate any effect of age, time to initiate treatment, and
average albumin on mortality estimates. Cumulative metaanalysis showed no change in the mortality
estimates with time.
Conclusion: There was no mortality effect with the type of nutritional supplementation. Although early
EN significantly reduced complication rates, this needs to be interpreted in the light of missing data and
heterogeneity. The enthusiasm that early EN, as compared with early PN, would reduce mortality
appears misplaced.
Peck. Early Enteral Nutrition Does Not Decrease Hypermetabolism Associated with Burn Injury. J
Trauma57:1143-1149. Dec 2004. Peck.
Background: A prospective, randomized study was performed to compare the effects of early versus late
enteral feeding on postburn metabolism.
Methods: Burn patients were randomized to receive enteral feedings either within 24 hours (early) or 7
days (late) of injury. Results: Average age, burn size, infections, and length of stay were similar between
groups. Mortality between groups was similar (early, 28%; late, 38%) and not significantly influenced by
inhalation injury. When controlled for percentage of total body surface area burn, inhalation injury, and
age, the early group had an increased rather than decreased DEE, with a mean DEE calorie 0.17 more
than the late group (p = 0.07). Conclusion: Early enteral feeding does not decrease the average energy
expenditure associated with burn injury.
EAST: Practice management guidelines for nutritional support of the trauma patient.
http://www.guideline.gov/summary/summary.aspx?doc_id=2961 . (volver)
Level I:
. There is sufficient Level I and II data to support use of early intragastric feedings in burns as soon after
admission as possible since delayed enteral feeding (>18 hours) results in a high rate of gastroparesis and
need for intravenous nutrition. A high success rate of intragastric feeding occurs when feedings are
started within 12 hours of burn.
. Literature regarding enhanced formulation in burned patients is not conclusive.
. There appears to be NO advantage to the routine use of calorimetry to determine the caloric
requirements of burn patients.
Level II:
. For patients with burns exceeding 20% to 30% total body surface area (TBSA), initial caloric
requirements may be estimated by any of several available formulas.
. The Curreri Formula (25 kcal/kg + 40 kcal/total body surface area burn) overestimates caloric needs of
the burn patient (as estimated by calorimetry) by 25% to 50%.
. The Harris-Benedict Formula underestimates the caloric needs of the burn patient (as estimated by
calorimetry) by 25% to 50%.
. In patients with burns exceeding 50% total body surface area, total parenteral nutrition (TPN)
supplementation of enteral feedings in order to achieve Curreri-predicted caloric requirements is
associated with higher mortality and aberrations in T-cell function.
. Caloric requirements for major burns fluctuate throughout the hospital course, but appear to follow a
biphasic course with energy expenditure declining as the burn wound closes. Therefore, direct
measurement of energy expenditure via calorimetry on a once or twice weekly basis may be of benefit in
adjusting caloric support throughout the hospital course.
. Intra-operative enteral feeding of the burn patient is safe and efficacious, leads to fewer interruptions in
the enteral feeding regimen, and therefore more successful attainment of calorie and protein goals.
. Approximately 1.25 grams of protein per kg body weight is appropriate for most traumatized patients.
. Up to 2 grams of protein per kg body weight per day is appropriate for severely burned patients.
16
. In the burn patient, energy as carbohydrate may be provided at a rate of up to 5 mg/kg/min
(approximately 25 kcal/kg/day); exceeding this limit may predispose patients to the metabolic
complications associated with overfeeding. In the non-burn trauma patient, even this rate of carbohydrate
delivery may be excessive.
. Intravenous lipid or fat intake should be carefully monitored and maintained at <30 percent of total
calories. Zero fat or minimal fat administration to burned or traumatically injured patients during the
acute phase of injury may minimize the susceptibility to infection and decrease length of stay.
. Proteins, fat and carbohydrate requirements do not appear to vary significantly according to the route of
administration, either enterally or parenterally.
. Fat or carbohydrate requirements do not appear to vary significantly according to the type of injury, i.e.,
burned versus traumatically injured.
Level III:
. Energy requirements for patients with less than 20% to 30% total body surface area burns are similar to
those of patients without cutaneous burns.
. Protein requirements in burn patients and in those with severe central nervous system (CNS) injuries
may be significantly greater than anticipated, up to 2.2 grams/kg body weight per day. However, the
ability to achieve positive nitrogen balance in a given patient varies according to the phase of injury.
. Provision of large protein loads to elderly patients, or to those with compromised hepatic, renal or
pulmonary function may lead to deleterious outcomes.
Jacobs. the EAST Practice Management Guidelines Work Group. Practice Management Guidelines for
Nutritional Support of the Trauma Patient. Journal of Trauma-Injury Infection & Critical Care.
57(3):660-679, September 2004. Jacobs. (volver)
Level II:
. In burn patients, intragastric feedings should be started as soon after admission as possible, because
delayed enteral feeding (>18 hours) results in a high rate of gastroparesis and need.
. Patients with burns exceeding 50% TBSA should not receive TPN supplementation of enteral feedings
to achieve Curreri-predicted caloric requirements, as this is associated with higher mortality and
aberrations in T-cell function.
. Once- or twice-weekly determination of energy expenditure via calorimetry may be of benefit in
avoiding over- and underfeeding in patients with severe burns.
. Burn patients that require frequent burn wound debridement should have their enteral feedings continued
intraoperatively, as this practice is safe and leads to more successful attainment of calorie and protein.
. Approximately 1.25 g of protein per kilogram of body weight per day should suffice for most injured
patients, whereas up to 2 g of protein per kilogram of body weight per day is appropriate for severely
burned patients.
8. Carbohydrate administration should not exceed 5 mg/kg/min (~25 kcal/kg/d) for burn patients, and
even less for nonburn trauma patients. Exceeding these limits may predispose patients to the metabolic
complications associated with overfeeding.
9. Intravenous lipid or fat intake should be carefully monitored and maintained at less than 30% of total
calories. Zero fat or minimal fat administration to burned or traumatically injured patients during the
acute phase of injury may minimize the susceptibility to infection and decrease length of stay.
. Until larger studies with improved methodology are completed, only a relatively weak recommendation
can be made in severely injured patients (ISS > 20, ATI > 25) for the use of enteral formulations
enhanced by the addition of arginine and/or glutamine. The specific impact of further supplementation
with omega-3 fatty acids, nucleotides, and trace elements cannot be determined at this time. Similarly, the
current literature gives no support to recommendations regarding the use of enhanced enteral formulas in
patients with severe burns.
Ye-Ping Zhou. The effects of supplemental glutamine dipeptide on gut integrity and clinical outcome
after major escharectomy in severe burns: a randomized, double-blind, controlled clinical trial. Clinical
Nutrition Supplements, Volume 1, Issue 1, 2004, Pages 55-60. (volver)
Objective: To evaluate the effects of glutamine dipeptides on gut permeability, plasma endotoxin and
outcome variables following extensive eschar excision on severe burns.
Methods: Thirty patients with severe burns (total body surface burns, 30–50% and third degree
burns, 15–25%) were investigated in a prospective, randomized, double-blind clinical trial, to receive
parenteral nutrition with (test group) or without (control group) glutamine dipeptide supplementation.
Parenteral iso-energetic and iso-nitrogenous nutrition was initiated on postoperative day 1 (POD+1) and
was administered to both groups until postoperative day 12 (POD+12). Glutamine dipeptide supplement
(Dipeptiven®, Fresenius Kabi, Bad Homburg, Germany) corresponded to 0.5 g/kg bw/d (equal to 0.35 g
17
glutamine kg bw/d). Plasma glutamine (gln-p), serum endotoxin concentrations, and the
lactulose/mannitol absorption ratio (L/M, which reflects gut permeability) were measured throughout the
clinical course. Survival rate of skin graft, wound healing time and infection rate were assessed and
length of hospital stay and total costs were determined at discharge.
Results: The concentrations of gln-p remained low in the control group, but increased in the supplemented
group (POD+1: control, 321±40 μmol/l, vs. test 431±52 μmol/l, P<0.001; POD+12: control,
397±38 μmol/l, vs. test 532.1±48.9 μmol/l, P<0.001). L/M ratio was initially increased in both groups,
reflecting enhanced intestinal permeability; the levels being normalized at POD+12. Endotoxin levels
were equally elevated in both groups at commencement (POD+1), but decreased significantly in patients
receiving gln (POD+12: control, 0.141±0.045 vs. test 0.112±0.026, P<0.043). Wound healing time was
significantly shorter in the gln group compared to controls (32±3 days vs. 37±6, P<0.012). Infection
rate revealed an obviously lower tendency (control: 26% vs. test 13% NS), yet without approaching a
significant difference. The skin graft survival rate and length of hospital stay were not significantly
different between the groups.
Conclusion: Supplementation with glutamine dipeptide was associated with enhanced gln plasma
concentrations, decreased gut permeability and endotoxin levels as well as wound healing time and
lower cost of hospitalization.
Peng X. Analysis of efficacy and safety of glutamine granules in severely burned patients. Annals of
Burns and Fire Disasters - vol. XVII - n. 2 - June 2004
SUMMARY. In order to evaluate the clinical therapeutic effect and safety of glutamine granules on
severe burn patients, 48 severely burned patients were randomly divided into two groups: a burns control
group (B group, 23 patients) and a glutamine granules treatment group (GLN group, 25 patients). The
GLN group patients were given glutamine granules 0.5 g/kg daily for 14 days and the B group received
the same dosage of placebo for 14 days. The plasma glutamine concentration, the degree of intestinal
mucosa damage, blood biochemistry, and complications were observed. The results show that after 14
days of oral administration of glutamine granules, the plasma glutamine concentration in the GLN group
was significantly higher than in the B group (p < 0.01). The degree of intestinal damage and intestinal
mucosa permeability in the GLN group was lower than that in the B group. This indicates that orally
supplemented glutamine could reduce the degree of intestinal injury and lessen intestinal mucosal
permeability. There was no evidence of any side effects.
Hart, Herndon. Effects of Early Excision and Aggressive Enteral Feeding on Hypermetabolism,
Catabolism, and Sepsis after Severe Burn. J Trauma 54(4) pp 755-764. April 2003. Herndon. (volver)
Background : Severe burn induces a systemic hypermetabolic response, which includes increased energy
expenditure, protein catabolism, and diminished immunity. We hypothesized that early burn excision and
aggressive enteral feeding diminish hypermetabolism.
Methods : Forty-six burned children were enrolled into a cohort analytic study. Cohorts were segregated
according to time from burn to transfer to our institution for excision, grafting, and nutritional support. No
subject had undergone wound excision or continuous nutritional support before transfer. Resting energy
expenditure, skeletal muscle protein kinetics, the degree of bacterial colonization from quantitative
cultures, and the incidence of burn sepsis were measured as outcome variables.
Results : Early, aggressive treatment did not decrease energy expenditure; however, it did markedly
attenuate muscle protein catabolism when compared with delay in aggressive treatment. Wound
colonization and sepsis were diminished in the early treatment group as well.
Conclusion : Early excision and concurrent aggressive feeding attenuate muscle catabolism and
improve infectious outcomes after burn.
Dr. David W. Hart (closing): Regarding different mediators after severe burn that may affect either
hypermetabolism or catabolism, yes, it is thought that there are different hormonal mediators.
Specifically, catecholamines are thought to be the primary mediators of elevated energy expenditure after
burn. In contrast, cortisol is thought to be the main mediator of muscle protein catabolism after severe
systemic stress such as burn injury. We are planning on measuring serial catecholamine and cortisol
levels in burn patients from the time of injury, through acute hospitalization, and through the
convalescence period.
Dr. Hoyt asked about our choice of an elemental diet for interval feeding in this study. The diet that we
used for this study was Vivonex TEN. It is the standard diet that we feed burned patients at our
institution. We reported, at this year’s Surgical Infection Society meeting, that this high-carbohydrate,
high-protein, low-fat diet improves muscle protein kinetics. It induces an endogenous insulin response in
catabolic burn patients, which lessens their negative net protein balance. That is the reason we chose this
diet. We have not seen any detrimental effects such as increased sepsis or difficulty weaning mechanical
18
ventilatory support (because of the high carbohydrate load) secondary to this diet. As I said before, this is
the diet that our institution has used for the last 4 years, and we have had the lowest pediatric burn
mortality in the world
Regarding the use of anabolic agents, none of the patients in this study received any anabolic agent before
or during the study periods. I believe that Dr. Pruitt is correct in his assumption that anabolic agents can
improve muscle protein balance. Our institution has performed several studies in critically ill burn
patients showing successful alteration of the catabolic response to burn using growth hormone, insulin,
insulin-like growth factor 1, oxandrolone, propranolol, and testosterone. In all of these studies (except
for the propranolol study), anabolic agents improved muscle protein balance but did not alter energy
expenditure. This, in and of itself, is evidence that hypermetabolism and protein catabolism are not
directly coupled processes in all circumstances
Andel. Nutrition and anabolic agents in burned patients. Burns, 29(6), 2003, 592-595 . Andel. (volver)
Recent findings: Major themes discussed in recent literature are dealing with enteral versus parenteral
nutrition and gastric versus duodejal feeding. The possibility of overfeeding is another important aspect of
high calorie nutrition as commonly used in burned patients. Specific formulas for enteral nutrition for
specific metabolic abnormalities are under evaluation as well as the role of anabolic and anticatabolic
agents.
Summary: From the clinical literature, total enteral nutrition starting as early as possible without any
supplemental parenteral nutrition is the preferred feeding method for burned patients. Using a duodenal
approach, especially in the early postburn phase, seems to be superior to gastric feeding. Administration
of high calorie total enteral nutrition in any later septic phase should be critically reviewed due to possible
impairment of splanchnic oxygen balance. Therefore, measurement of CO 2-gap should be considered as a
monitoring method during small bowel nutrition.
The impact on the course of disease of supplements such as arginine, glutamine and vitamins as well as
the impact of the use of anabolic and anticatabolic agents is not yet evident. Furthermore, the effect of
insulin administration and low blood sugar regimes on wound healing and outcome in burned patients
should be evaluated in future studies.
However, there is growing evidence that agents such as glutamine, have positive impact on metabolic
management and thereby on morbidity and outcome in severely burned patients. On the other hand the
overall effect of glutamine in humans is still under discussion, because limited data are available
concerning the mechanism for any of the glutamines purported effects. Moreover, whether these effects
are based on altered cellular physiology, metabolic regulation, or regulation of gene expression is still
unclear.
Arginine has been shown to have a wide variety of potentially beneficial metabolic effects, since it serves
multiple roles in the pathophysiological response in injured and critical patients. The rate of arginine
degradation is markedly increased after burn, whereas synthesis remains constant, leading to a deficiency
state.
Nutritional intervention using omega-3 fatty acid leads a more rapid recovery of serum insulin like
growth factor (IGF) levels with consecutive beneficial effects on wound healing.
In spite of the fact that agents such as human growth hormon (hGH), the testosterone derivative
oxandrolone and IGF reduce catabolism and muscle mass reduction, the impact of hGH on the course
of disease and its outcome is still controversial.
Further on, low-dose insulin has anabolic effects and might have a beneficial effect on the outcome.
Hyperglycemia or relative insulin deficiency, or both during critical illness may confer a predisposition to
complications, such as severe infections, multiple organ failure and death. High calorie fed critically ill
burned patients are at special risk for development of high blood sugar levels.
A completely different approach in the treatment of catabolism is the use of β -blocking agents in severe
burned patients. At least in burned children administration of propanolol attenuates hypermetabolism
and reverses muscle–protein catabolism without side effects on wound healing. Beside this, β -blockade
of septic patients is contrary to the hyperperfusion-concept of Shoemaker et al. Although this concept has
been widely discussed, regional hypoperfusion, even without β -blockade, is a known problem in septic
burned patients.
The overall effect of - β blockade on the outcome of severely burned children and adults is still not
known, as less catabolism does not necessarily result in a better survival rate.
Saffle. What’s new in general surgery: burns and metabolism. Journal of the American College of
Surgeons, Volume 196, Issue 2, February 2003, Pages 267-289
Provision of the amino acid glutamine (GLN) is widely thought to be important as a specific nutrient for
both enterocytes and lymphocytes, to reduce mucosal atrophy, and ameliorate bacterial translocation.
19
Wischmeyer and colleagues evaluated the effect of parenteral GLN supplementation in randomized
controlled clinical trial among 26 patients with severe burns. The use of GLN was associated with a
significant decrease in gram-negative bacteremia (8% versus 43%, p < 0.04), increases in transferrin and
prealbumin, and reduction in C-reactive protein, compared with values in control patients. Mortality was
not notably reduced. This interesting paper warrants several comments. First, this is a very small study; its
results will need to be validated in larger trials before being accepted. Second, most studies of GLN
efficacy have used enteral GLN to supplement parenteral nutrition (standard total parenteral nutrition
formulas contain no GLN, which is relatively insoluble). These authors did the opposite and used large
doses of GLN (0.57 g/kg/day). Their patients were fed a standard enteral formula containing no
supplementary GLN. In contrast, most trauma and burn surgeons use specially designed stress formulas
supplemented with arginine,ω-3 fatty acids, and GLN (in doses roughly equivalent to those used here).
These formulas have been shown to enhance protein synthesis, and reduce infectious complications and
oxidative stress in a variety of settings, including recent studies in burns. Although the study by
Wischmeyer’s group appears to validate the benefit of GLN as a nutrient for burn patients, it would be
helpful to know if specific GLN supplementation adds anything to the use of commercially available
stress formulas.
Mediation of hypermetabolism
The foremost group in this area continues to be led by Dr David Herndon at the Shriners’ Burns
Institute in Galveston, TX. They have evaluated a number of modalities for ameliorating
hypermetabolism, including reduction of metabolic rate using propranolol, administration of counterregulatory hormones such as insulin and insulin-like growth factor (IGF), and stimulating anabolism
using growth hormone, natural steroids, and synthetic products such as oxandrolone.
Propranolol : A study from Galveston randomized 56 children with major burns to receive supplemental
growth hormone, propranolol, or both. Propranolol markedly reduced resting heart rate and energy
expenditure, measured by indirect calorimetry, and improved net muscle protein synthesis. Interestingly,
the addition of growth hormone did not increase these effects. These benefits of propranolol treatment
were confirmed in another prominent study by this group.
Propranolol also appears to reduce the rate of hepatic fat accumulation. There was a clear association
between fatty liver and systemic sepsis, suggesting hepatic dysfunction, not overfeeding, as the cause of
this finding.
Insulin: Thomas and coworkers evaluated the effect of continuous infusions of insulin (to maintain blood
glucose between 100 and 140 mg/dL) on preservation of muscle mass in a randomized controlled clinical
trial in 18 children with major burns. Evaluation of each patient when 95% healed showed that insulintreated patients had improved lean body mass, less muscle wasting, and reduced length of hospital stay,
compared with controls. In an animal study, daily administration of subcutaneous insulin to burned rats
resulted in reduced protein degradation in both skeletal muscles and immune cells.
In a review of diabetic burn patients, McCampbell and associates found that patients with diabetes with
uncontrolled blood glucose levels (defined as values greater than 180 mg/dL on more than 50% of
determinations) had higher rates of infection and longer lengths of hospitalization than patients with
diabetes with controlled blood glucose levels, confirming the clinical importance of careful control of
blood sugar in burn patients.
Insulin-like growth factor
Gianotti and colleagues studied temporal fluctuations in IGF-1 and its binding protein in a group of burn
patients, and demonstrated that both proteins declined for the first 14 days postburn, paralleling decreases
in prealbumin and transferrin; plasma levels of growth hormone remained unchanged. In a small trial in
children, administration of IGF-1 and IGF binding protein appeared to exert widespread effects in
ameliorating acute inflammation by reducing the synthesis of type I and II acute phase proteins, and IL-6,
and increasing synthesis of constitutive proteins, such as prealbumin and transferrin.
Alterations in IGF-I seen after burn injury appear to be mediated at least partially by glucocorticoids.
Lang and coauthors demonstrated that administration of a glucocorticoid antagonist prevented burninduced decreases in plasma IGF-I, and associated muscle wasting. Antagonists to TNF-α had no effect
on these measurements.
Sex hormones: The effect of male and female sex hormones in burn injury was investigated in several
studies. In male mice, administration of 17β-estradiol after burn injury restored delayed-type
hypersensitivity, reduced macrophage production of IL-6, and increased survival after bacterial challenge.
The ability of testosterone and of synthetic male hormone analogs such as oxandrolone to promote
muscle anabolism and wound healing has previously been examined in a number of studies. Ferrando and
coworkers administered intramuscular testosterone to six severely burned male patients, and evaluated
testosterone levels and protein synthetic activity before, during, and after hormone administration. They
found no change in protein synthesis, but there was a twofold decrease in protein breakdown, resulting in
20
a net improvement in protein balance. Napolitano pointed out that there is some evidence that males have
increased mortality and risk of infection after injury and that testosterone appears to have an
immunosuppressive effect, including suppression of IL-2 and IL-3 release. This suggests that clinical use
of testosterone will need to be evaluated extremely carefully.
How should practicing clinicians apply the results of these multiple trials of metabolic mediators? At
present, the most immediately useful and probably least controversial intervention would be careful
control of serum glucose. A recent large multicenter randomized controlled clinical trial in intensive care
unit patients confirmed that careful regulation of blood sugar reduces infectious complications and overall
mortality. The results reviewed here suggest that clinicians should be aggressive in treating this
abnormality and in monitoring the effects of insulin administration.
In addition, propranolol is being used more and more for a variety of indications in surgical patients—it
also reduces tremors and anxiety in surgeons! It appears to be a reasonably safe intervention, though the
effects of β-blockade on protein metabolism have not resulted in major clinical improvements.
Tachycardia and hyperdynamic cardiac function are often apparent in burn patients, and use of this agent
to reduce these findings seems reasonable. But this drug, like insulin, can have major side effects;
practitioners will need to remain vigilant when administering - β blockers to critically ill burn patients.
Anabolic steroids, including testosterone and analogs like oxandrolone, are also widely used to
ameliorate muscle wasting in patients with cancer and AIDS. Previous studies have suggested limited
benefits associated with its use in burn patients. But before any of these modalities should be regarded as
proved therapies, they will need to be confirmed in large, preferably multicenter, randomized clinical
trials. Such a trial is currently underway within the ABA. Hopefully, the next few years will see more
such trials.
Growth factors :Circulating growth factors are widely recognized to affect many aspects of burn wound
healing. Cribbs and colleagues documented increased production of heparin-binding epidermal growth
factor-like growth factor, and transforming growth factor-alpha (TGF-α) in epidermal cells after burn
injury in mice. Levels of circulating TGF- β, a potent immunosuppressive cytokine, increased
progressively for 8 days after burn injury in a rat model, but levels of IL-4, which is thought to regulate
TGF- β secretion, remained undetected. TGF- β 1 was also shown to increase in thymic tissue after burns
in mice, with associated increased apoptosis and loss of thymic cell mass, while levels of smad-2 and 3,
transcription factors that ameliorate the effects of TGF- β 1, were reduced. This suggests a change in the
balance and regulation of TGF-1 β activity and a mechanism for some of its immunosuppressive effects.
Yang and coauthors found elevated numbers of circulating fibroblasts, a newly described type of cell, in
the blood of burn patients for up to a year after injury. These cells can play an important role in wound
healing and scarring after burn injury. Numbers of cells correlated with burn injury size, and with levels
of TGF-1 β, suggesting systemic activation of this cell population.
The potential might now exist to deliver growth factors more effectively through gene transfer
technology. Keratinocyte growth factor stimulates epidermal proliferation, but has been ineffective when
applied topically, presumably because of enzymatic inactivation.
Garrel. Montreal. Decreased mortality and infectious morbidity in adult burn patients given enteral
glutamine supplements: a prospective, controlled, randomized clinical trial. Crit Care Med. 2003
Oct;31(10):2444-9. Comment in Crit Care Med. 2003 Oct;31(10):2555-6. GarrelGarrel. (volver)
OBJECTIVE: Enteral glutamine supplements have been shown to reduce infectious morbidity in trauma
patients, but their effect on burn patients is not known. DESIGN: Double-blinded, randomized clinical
trial. SETTING: Burn center. PATIENTS: Forty-five adults with severe burns. INTERVENTIONS:
Patients were randomized to receive either glutamine or an isonitrogenous control mixture until complete
healing occurred. Upon insertion of the feeding tube, the patients received either 4.3 g of G (Cambridge
Neutraceutical, Boston, MA) every 4 hrs, for a total of 26 g/day, or an isonitrogenous mixture of aspartic
acid, asparagine, and glycine. Amino acids and G were administered in 50 mL of sterile water through the
feeding tube. G or the amino acid mixture was continued even when enteral nutrition was interrupted for
surgical procedures. G or amino acids were given until the end of the study, which was determined as the
time to complete wound healing.
Four patients were excluded from the analysis, because three of them died within 72 hrs and the fourth
could not receive enteral nutrition and amino acid supplements for the first 10 days. Of the remaining 41
patients, length of care in the survivors was not different between groups (0.9 vs. 1.0 days/percent total
body surface area for glutamine vs. control, respectively), positive blood culture was three times more
frequent in control than in glutamine treatment (4.3 vs. 1.2 days/patient, p <.05), and Pseudomonas
aeruginosa was detected in six patients on control and zero on glutamine (p <.05). Phagocytosis by
polymorphonuclear cells was not different between groups. Mortality rate was significantly lower in
glutamine than in control: intention to treat, two vs. 12 (p <.05); per protocol analysis, zero vs. eight (p
21
<.01). CONCLUSIONS: Enteral glutamine supplementation in adult burn patients reduces blood
infection by a factor of three, prevents bacteremia with P. aeruginosa, and may decrease mortality
rate. It has no effect on level of consciousness and does not appear to influence phagocytosis by
circulating polymorphonuclear cells.
Gottschlich. The 2002 Clinical Research Award: an evaluation of the safety of early vs delayed enteral
support and effects on clinical, nutritional, and endocrine outcomes after severe burns. J Burn Care
Rehabil. 2002;23:401–15. Gottschlich. (volver)
Early enteral support is believed to improve gastrointestinal, immunological, nutritional, and metabolic
responses to critical injury; however, this premise is in need of further substantiation by definitive data.
The purpose of this prospective study was to examine the effectiveness and safety of early enteral feeding
in pediatric patients who had burns in excess of 25% total body surface area. Seventy-seven patients with
a mean percent total body surface area burn of 52.5 ± 2.3 (range 26–91), percent full thickness injury of
44.7 ± 2.8 (range 0–90), and age ranging from 3.1 to 18.4 (mean 9.3 ± 0.5) were randomized to two
groups: early (feeding within 24 hours of injury) vs control (feeding delayed at least 48 hours postburn).
No differences were evident in infection, diarrhea, hospital length of stay, or mortality outcomes. A
higher incidence ob reportable adverse events coincided with early feeding (22 vs 8%), but this was
not statistically significant. The delayed feeding group demonstrated a significant caloric deficit during
postburn week (PBW) 1 (P < .0001) and PBW2 (P = .0022). Serum insulin (P = .0004) and
triiodothyronine (P =.0162) were higher in the early fed group during PBW1. A decrease in 3methylhistidine output (suggesting a decrease in protein breakdown) was also evident during PBW1 (P =
.0138). In conclusion, provision of enteral nutrients shortly after burn injury reduces caloric deficits and
may stimulate insulin secretion and protein retention during the early phase postburn. These data,
however, do not necessarily reaffirm the safety of early enteral feeding, nor do they associate earlier
feeding with a direct improvement in endocrine status or a reduction in morbidity, mortality,
hypermetabolism, or hospital stay.
Herndon, C. Nutritional intervention high in vitamins, protein, amino acids, and omega 3 fatty acids
improves protein metabolism during the hypermetabolic state after thermal injury. Arch. Surg. 136, 11
(2001), pp. 1301–1306
Intervention Twenty-two rats were given burns covering 60% of their total body surface area and
randomized to receive either standard rat chow (control) or a diet high in vitamins, protein, amino acids,
and 3 fatty acids. Results Rats receiving the enriched diet showed a gradual improvement in body
weight 1, 2, 3, 4, and 5 weeks postburn compared with controls (P<.001). Diet-fed rats demonstrated
higher protein and insulin-like growth factor 1 content in serum, muscle, and liver 5 weeks after trauma
(P<.001). Serum protein, albumin, and transferrin levels were significantly increased in rats receiving the
diet compared with control rats (P<.001). Reepithelization was accelerated in rats receiving the enriched
diet 4 (diet-fed, mean ± SD, 23% ± 1% vs controls, 17% ± 1%; P<.001) and 5 (diet-fed, 24% ± 1% vs
controls, 18% ± 1%; P<.001) weeks postburn compared with control rats.
Conclusions Nutritional intervention high in protein, vitamins, amino acids, and 3 fatty acids improves
protein net balance during the hypermetabolic response to thermal injury. Compromised organ function
and structure and clinical outcome during the hypermetabolic response may be improved.
Hart,Herndon, DN. Attenuation of post-traumatic muscle catabolism and osteopenia by long-term
growth hormone therapy. (2001). Ann Surg. 2001 Jun;233(6):827-34.
Seventy-two severely burned children were enrolled in a placebo-controlled double-blind trial
investigating the effects of growth hormone (0.05 mg/kg per day) on muscle accretion and bone growth.
Drug or placebo treatment began on discharge from the intensive care unit and continued for 1 year after
burn. Total body weight, height, dual-energy x-ray absorptiometry, indirect calorimetry, and hormone
values were measured at discharge, then at 6 months, 9 months, and 12 months after burn. Results were
compared between groups. RESULTS: Growth hormone subjects gained more weight than placebo
subjects at the 9-month study point; this disparity in weight gain continued to expand throughout the
remainder of the study. Height also increased in the growth hormone group compared with controls at 12
months. Change in lean body mass was greater in those treated with growth hormone at 6, 9, and 12
months. Bone mineral content was increased at 9 and 12 months; this was associated with higher
parathormone levels. CONCLUSIONS: Low-dose recombinant human growth hormone successfully
abates muscle catabolism and osteopenia induced by severe burn.
Prelack K, Sheridan RL. Micronutrient supplementation in the critically ill patient: strategies for
clinical practice. J Trauma. 2001 Sep;51(3):601-20. Prelack. (volver)
22
Moderate supplementation of the trace elements zinc, copper, and selenium in addition to standard
nutritional therapy are recommended. Adequate intakes for zinc and copper are likely achieved with the
daily provision of a multivitamin with trace element supplement, although additional supplementation
may be required, particularly in more severe burn injury. In addition, vitamin C provided at what appears
to be a threshold level of intake (after which plasma levels plateau) is given. Although evidence suggests
that vitamin E becomes deficient, it is not supplemented per se. Rather, it is hoped that maintenance of
vitamin C (which can regenerate vitamin E) and selenium will maintain adequate vitamin E status.
Provision of B vitamins in standard enteral products aimed at meeting calorie and protein targets should
be sufficient
Wyncoll, Immunologically enhanced enteral nutrition: current status. Current Opinion in Critical Care.
7(2):128-132, April 2001. Wyncoll (volver)
This approach to modulating the immune and inflammatory responses has become known as
immunonutrition, and many products are now available for clinical use. Several have been subjected to
clinical study in various patient groups, with encouraging results in terms of reducing infection rates and
length of hospital stay. They appear to benefit both critically ill patients and patients undergoing major
surgery, particularly when feeding is started preoperatively. Two systematic reviews have been
published, both with positive results. Nevertheless, as new products become available they should be
subjected to controlled clinical trials, especially because several of the mechanisms involved are not yet
fully understood
Wilmore, The effect of glutamine supplementation in patients following elective surgery and accidental
injury. J. Nutr. 131 9 Suppl (2001), pp. 2543S–2549S discussion 2550S-1S .
Buchman, Glutamine: commercially essential or conditionally essential? A critical appraisal of the
human data. Am. J. Clin. Nutr. 74 1 (2001), pp. 25–32.
Gore, Deficiency in peripheral glutamine production in pediatric patients with burns. J. Burn Care
Rehabil. 21 2 (2000), p. 171 discussion 172-7 .
Houdijk, Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients
with multiple trauma. Lancet 352 9130 (1998), pp. 772–776.
► Vitamina C
Namias (Irwin-Rippe, 5ª edición del 2003): Augmentation of the resuscitation with ascorbic acid
(vitamin C) in a prospective randomized human trial has been shown to decrease the volume required for
resuscitation, decrease edema formation, improve oxygenation, and decrease the number of ventilator
days ]. The author routinely gives vitamin C by intravenous drip at 66 mg per kg per hour for the first 24
hours for burns serious enough to be admitted to the ICU. Rippe (volver).
Yanai, Vitamin c as therapy for burn shock patients. Plastic & Reconstructive Surgery. 112(3):942,
September 1, 2003.
Tanaka,. The choice of fluid resuscitation formula on major thermal injury: Clinical effectiveness of
vitamin C therapy. Jpn. J. Plast. Reconstr. Surg. 45: 721, 2002.
The main goal of fluid resuscitation during the early phase of burn treatment is to maintain an adequate
intravascular volume with a minimal amount of fluid. Oxygen free radicals are considered to play an
important role in increased vascular permeability and lipid peroxidation after severe thermal burn injury.
To drastically improve the pathophysic change after burn, the authors studied high-dose vitamin C
therapy as a potent natural antioxidant, both experimentally and clinically. Both the basic experiments
and the clinical studies indicate that the adjuvant administration of vitamin C led not only to clear
reduction in resuscitation fluid but also to a reduction in burn edema, lipid peroxidation, and respiratory
impairment after severe thermal injury. The authors conclude that vitamin C can be extremely useful as a
new therapy for use during the burn shock period.
Tanaka: Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid
administration: a randomized, prospective study. Arch Surg 135(3):326–331, 2000
► Infección
23
Weber. Infection control in burn patients. Burns, Vol 30:8, December 2004, Pages A16-A24. Weber
(volver)
Ansermino. ABC of burns: Intensive care management and control of infection. BMJ 2004;329:220-223.
(Es parte de una serie de 12 artículos en el BJM del 5Jun04 en adelante, que cubren los principales
aspectos del ttº a los quemados). Ansermino
Advantages and adverse effects of topical antimicrobials
Silver sulfadiazine
• Water soluble cream
• Advantages—Broad spectrum, low toxicity, painless
• Adverse effects—Transient leucopenia, methaemoglobinaemia (rare)
Cerium nitrate-silver sulfadiazine
• Water soluble cream
• Advantages—Broad spectrum, may reduce or reverse immunosuppression after injury
• Adverse effects—As for silver sulfadiazine alone
Silver nitrate
• Solution soaked dressing
• Advantages—Broad spectrum, painless
• Adverse effects—Skin and dressing discoloration, electrolyte disturbance, methaemoglobinaemia (rare)
Mafenide
• Water soluble cream
• Advantages—Broad spectrum, penetrates burn eschar
• Adverse effects—Potent carbonic anhydrase inhibitor—osmotic diuresis and electrolyte imbalance, painful
application
Tredget. Pseudomonas infections in the thermally injured patient .Burns, Volume 30, Issue 1, February
2004, Pages 3-26
Herruzo. Two consecutive outbreaks of Acinetobacter baumanii 1-a in a burn Intensive Care Unit for
adults.Burns, Volume 30, Issue 5, August 2004, Pages 419-423
24
Barret JP, Herndon. Effects of burn wound excision on bacterial colonization and invasion. Plast
Reconstr Surg. 2003 Feb;111(2):744-50; discussion 751-2. Barret. (volver)
Early excision has been advocated as one of the major factors, but its safety and efficacy and the exact
timing of burn excision are still under debate. It was hypothesized that acute burn wound excision (in the
first 24 hours after burning) would be superior to conservative treatment and delayed excision in
preventing bacterial colonization and invasion. Twenty consecutive patients with thermal injuries were
studied. Twelve patients underwent acute burn wound excision, and eight patients underwent
conservative treatment and delayed excision. The second group of patients received topical treatments in
another facility and underwent delayed excision after transfer to our service, on postburn day 6. Patients
admitted early exhibited bacterial counts of less than 10 bacteria per gram of tissue. Patients in this group
did not experience infection or graft loss. Patients admitted late exhibited counts of more than 10 bacteria
(p = 0.001, compared with early admission). Three patients in the late excision group experienced
infection and graft loss (p < 0.05, compared with the early excision group). Burn wound excision
significantly decreased bacterial colonization for all patients (p < 0.001). Greater bacterial
colonization and higher rates of infection were correlated with topical treatment and late excision (p <
0.001). It is concluded that burn wound excision significantly reduces bacterial colonization. Patients who
undergo topical treatment and delayed burn wound excision exhibit greater bacterial colonization and
increased rates of infection. Acute burn wound excision should be considered for all full-thickness burns.
Hart. Effects of early excision and aggressive enteral feeding on hypermetabolism after severe burn. J
Trauma 54:755-764. 2003. Hart. (volver)
Background : Severe burn induces a systemic hypermetabolic response, which includes increased energy
expenditure, protein catabolism, and diminished immunity. We hypothesized that early burn excision and
aggressive enteral feeding diminish hypermetabolism.
Methods : Forty-six burned children were enrolled into a cohort analytic study.
Results : Early, aggressive treatment did not decrease energy expenditure; however, it did markedly
attenuate muscle protein catabolism when compared with delay in aggressive treatment. Wound
colonization and sepsis were diminished in the early treatment group as well.
Conclusion : Early excision and concurrent aggressive feeding attenuate muscle catabolism and improve
infectious outcomes after burn.
Edge. Clinical outcome of HIV positive patients with moderate to severe burns. Burns, Volume 27, Issue
2, March 2001, Pages 111-114
Barret, Herndon DN.Biobrane versus 1% silver sulfadiazine in second-degree pediatric burns. Plast
Reconstr Surg. 2000 Jan;105(1):62-5. Shriners Burns Hospital and the University of Texas Medical
Branch, Galveston, USA. j.p.barret.nerin@chir.azg.nl (volver)
Partial-thickness burns in children have been treated for many years by daily, painful tubbing, washing,
and cleansing of the burn wound, followed by topical application of antimicrobial creams. Pain and
impaired wound healing are the main problems. We hypothesized that the treatment of second-degree
burns with Biobrane is superior to topical treatment. Twenty pediatric patients were prospectively
randomized in two groups to compare the efficacy of Biobrane versus 1% silver sulfadiazine. The rest of
the routine clinical protocols were followed in both groups. Demographic data, wound healing time,
length of hospital stay, pain assessments and pain medication requirements, and infection were analyzed
and compared. Main outcome measures included pain, pain medication requirements, wound healing
time, length of hospital stay, and infection. The application of Biobrane to partial-thickness burns proved
to be superior to the topical treatment. Patients included in the biosynthetic temporary cover group
presented with less pain and required less pain medication. Length of hospital stay and wound healing
time were also significantly shorter in the Biobrane group. None of the patients in either group presented
with wound infection or needed skin autografting. In conclusion, the treatment of partial-thickness burns
with Biobrane is superior to topical therapy with 1% silver sulfadiazine. Pain, pain medication
requirements, wound healing time, and length of hospital stay are significantly reduced.
Biobrane®‚ está compuesto por colágeno biológico recubierto por dos capas de nailon y silicona. La
disponibilidad de apósitos biosintéticos temporales en forma de láminas y guantes, nos ha modificado de manera altamente beneficiosa el horizonte del tratamiento de las quemaduras. (Beltrá 2002)
25
► S. de Inhalación
Latenser, Barbara A. M.D., F.A.C.S. 1; Iteld, Lawrence M.D. 2 Smoke Inhalation Injury. Seminars in
Respiratory & Critical Care Medicine. 22(1):13-22, February 2001.
► Oxido Nítrico
Taylor RW, Zimmerman Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized
controlled trial. JAMA. 2004 Apr 7;291(13):1603-9
Critical Care Medicine, St Louis University/St John's Mercy Medical Center, St Louis, Mo, USA.
CONTEXT: Inhaled nitric oxide has been shown to improve oxygenation in acute lung injury.
OBJECTIVE: To evaluate the clinical efficacy of low-dose (5-ppm) inhaled nitric oxide in patients with
acute lung injury. DESIGN AND SETTING: Multicenter, randomized, placebo-controlled study, with
blinding of patients, caregivers, data collectors, assessors of outcomes, and data analysts (triple blind),
conducted in the intensive care units of 46 hospitals in the United States. Patients were enrolled between
March 1996 and September 1999. PATIENTS: Patients (n = 385) with moderately severe acute lung
injury, a modification of the American-European Consensus Conference definition of acute respiratory
distress syndrome (ARDS) using a ratio of PaO2 to FiO2 of < or =250, were enrolled if the onset was
within 72 hours of randomization, sepsis was not the cause of the lung injury, and the patient had no
significant nonpulmonary organ system dysfunction at randomization. INTERVENTIONS: Patients were
randomly assigned to placebo (nitrogen gas) or inhaled nitric oxide at 5 ppm until 28 days,
discontinuation of assisted breathing, or death. MAIN OUTCOME MEASURES: The primary end point
was days alive and off assisted breathing. Secondary outcomes included mortality, days alive and meeting
oxygenation criteria for extubation, and days patients were alive following a successful unassisted
ventilation test. RESULTS: An intent-to-treat analysis revealed that inhaled nitric oxide at 5 ppm did not
increase the number of days patients were alive and off assisted breathing (mean [SD], 10.6 [9.8] days in
the placebo group and 10.7 [9.7] days in the inhaled nitric oxide group; P =.97; difference, -0.1 day [95%
confidence interval, -2.0 to 1.9 days]). This lack of effect on clinical outcomes was seen despite a
statistically significant increase in PaO2 that resolved by 48 hours. Mortality was similar between groups
(20% placebo vs 23% nitric oxide; P =.54). Days patients were alive following a successful 2-hour
unassisted ventilation trial were a mean (SD) of 11.9 (9.9) for placebo and 11.4 (9.8) for nitric oxide
patients (P =.54). Days alive and meeting criteria for extubation were also similar: 17.0 placebo vs 16.7
nitric oxide (P =.89). CONCLUSION: Inhaled nitric oxide at a dose of 5 ppm in patients with acute lung
injury not due to sepsis and without evidence of nonpulmonary organ system dysfunction results in shortterm oxygenation improvements but has no substantial impact on the duration of ventilatory support or
mortality.
Eden, Arieh MD Low-Dose Inhaled Nitric Oxide in Patients with Acute Lung Injury: A Randomized
Controlled Trial. Survey of Anesthesiology. 48(6):279-280, December 2004
Fioretto. Acute and sustained effects of early administration of inhaled nitric oxide to children with acute
respiratory distress syndrome. Pediatric Critical Care Medicine. 5(5):469-474, September 2004.
Abstract Objective: To determine the acute and sustained effects of early inhaled nitric oxide on some
oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and
conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical
ventilation in children with acute respiratory distress syndrome.
Patients: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs.
Interventions: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of
patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy
group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000.
Measurements and Main Results: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs
after acute respiratory distress syndrome diagnosis with acute improvements in Pao2/Fio2 ratio (83.7%)
and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric
risk of mortality score, and mean airway pressure. Pao2/Fio2 ratio was lower (CTG, 116.9 +/- 34.5;
iNOG, 62.5 +/- 12.8, p < .0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3
[range, 16.3-70.4], p < .0001) in the iNOG. Prolonged treatment was associated with improved
26
oxygenation, so that Fio2 and peak inspiratory pressure could be quickly and significantly reduced.
Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18,
16.6%, p < .001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG,
12 [range, 6-26], p > .05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10
[range, 4-25], p > .05).
Conclusions: Early treatment with inhaled nitric oxide causes acute and sustained improvement in
oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality
rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of
mechanical ventilation are not changed.
Dellinger, Zimmerman . For the Inhaled Nitric Oxide in ARDS Study Group. Inhaled Nitric Oxide in
Acute Lung Injury. JAMA Volume 292(3) p 327–328. 21 July 2004
In Reply
In response to Dr Kaisers and colleagues, there had been only 2 other large published studies of inhaled
nitric oxide in patients with ARDS. 1,2 The first of these studies was halted early. It enrolled only patients
who increased their oxygenation status when challenged with inhaled nitric oxide prior to enrollment. In
that trial, the number of patients with improved signs of acute lung injury was not statistically different
between the 2 treatment groups, the primary end point of the trial. The design of our 2 trials was different
in that all patients were randomized and response status was not established. Our first study was a phase 2
study that was designed to ascertain safety and potentially link a dose effect to clinical outcome in
patients with ARDS. A post-hoc analysis suggested that there was a clinical benefit of inhaled nitric oxide
at 5 ppm among this group of patients. To test this hypothesis, our phase 3 study was completed, which
we believe was appropriate and needed
As stated in our article, we agree that the results of our trial do not address the utility of inhaled nitric
oxide as a potential rescue therapy for patients with life-threatening hypoxemia following maximal
standard therapies. We believe that further research in this critically ill subset of patients is warranted.
Pending such a trial, and as we stated, we believe that inhaled nitric oxide should be considered as
salvage therapy when life-threatening hypoxemia continues despite optimization of mechanical
ventilation.
Taylor,; Zimmerman,; Dellinger,; Straube,; for the Inhaled Nitric Oxide in ARDS Study Group LowDose Inhaled Nitric Oxide in Patients With Acute Lung Injury: A Randomized Controlled Trial. JAMA.
291(13):1603-1609, April 7, 2004.
Objective: To evaluate the clinical efficacy of low-dose (5-ppm) inhaled nitric oxide in patients with
acute lung injury.
Design and Setting: Multicenter, randomized, placebo-controlled study, with blinding of patients,
caregivers, data collectors, assessors of outcomes, and data analysts (triple blind), conducted in the
intensive care units of 46 hospitals in the United States. Patients were enrolled between March 1996 and
September 1999.
Patients: Patients (n = 385) with moderately severe acute lung injury, a modification of the AmericanEuropean Consensus Conference definition of acute respiratory distress syndrome (ARDS) using a ratio
of PaO2 to FiO2 of <=250, were enrolled if the onset was within 72 hours of randomization, sepsis was
not the cause of the lung injury, and the patient had no significant nonpulmonary organ system
dysfunction at randomization.
Interventions: Patients were randomly assigned to placebo (nitrogen gas) or inhaled nitric oxide at 5 ppm
until 28 days, discontinuation of assisted breathing, or death.
Results: An intent-to-treat analysis revealed that inhaled nitric oxide at 5 ppm did not increase the number
of days patients were alive and off assisted breathing (mean [SD], 10.6 [9.8] days in the placebo group
and 10.7 [9.7] days in the inhaled nitric oxide group; P =.97; difference, -0.1 day [95% confidence
interval, -2.0 to 1.9 days]). This lack of effect on clinical outcomes was seen despite a statistically
significant increase in PaO2 that resolved by 48 hours. Mortality was similar between groups (20%
placebo vs 23% nitric oxide; P =.54). Days patients were alive following a successful 2-hour unassisted
ventilation trial were a mean (SD) of 11.9 (9.9) for placebo and 11.4 (9.8) for nitric oxide patients (P
=.54). Days alive and meeting criteria for extubation were also similar: 17.0 placebo vs 16.7 nitric oxide
(P =.89).
Conclusion: Inhaled nitric oxide at a dose of 5 ppm in patients with acute lung injury not due to
sepsis and without evidence of nonpulmonary organ system dysfunction results in short-term
oxygenation improvements but has no substantial impact on the duration of ventilatory support or
mortality.
27
Sokol, * Inhaled Nitric Oxide for Acute Hypoxic Respiratory Failure in Children and Adults: A Metaanalysis. Anesthesia & Analgesia. 97(4):989-998, October 2003.
We systematically reviewed randomized controlled trials examining inhaled nitric oxide (INO) for the
treatment of acute respiratory distress syndrome or acute lung injury in children and adults. Qualitative
assessments of identified trials were made, and metaanalyses were performed according to Cochrane
methodology. Five randomized controlled trials (n = 535) met entry criteria. One study demonstrated
significant improvement in oxygenation in the first 4 days of treatment, with no difference after this.
There was no difference in ventilator-free days between treatment and placebo groups, and no specific
dose of INO was more advantageous than any other. INO had no effect on mortality in trials without
crossover of treatment failures to open-label INO (relative risk, 0.98; 95% confidence interval, 0.66-1.44).
Other clinical indicators of effectiveness, such as duration of hospital and intensive care stay, were
inconsistently reported. Lack of data prevented assessment of all outcomes. If further trials assessing INO
in acute respiratory distress syndrome or acute lung injury are to proceed, they should be stratified for
primary etiology, incorporate other modalities that may affect outcome, and evaluate clinically relevant
outcomes before any benefit of INO can be excluded.
Mussgrave, M. A. MD, PhD; Cartotto, R. C. MD, FRCSC Use of Nitric Oxide as an Adjuvant Therapy
in Respiratory Failure After Burn Injuries: FROM THE AUTHORS:. Journal of Burn Care &
Rehabilitation. 22(4):308-310, July/August 2000. Mussgrave (volver)
In our small study with burn patients placed on nitric oxide for respiratory failure, we observed a
difference in response to nitric oxide between patients with inhalation injury and those without. 1
Namely, burn patients with inhalation injury seemed to develop acute respiratory distress syndrome
(ARDS) relatively later in their course and tended to respond to inhaled NO more vigorously than burn
patients without significant inhalation who developed ARDS 2 secondary to a systemic inflammatory
response. Although the number of subjects was too small to reach statistical significance, there seemed to
be a trend in the data that suggested perhaps a differential mechanism for respiratory distress in these
patient types.
Mussgrave MA, Fingland R, Gomez M, Fish J, Cartotto R. The use of inhaled nitric oxide as adjuvant
therapy in patients with burn injuries and respiratory failure. J Burn Care Rehabil 2000; 21: 551–7
Inhaled nitric oxide (NO) is a relatively new modality in the management of acute respiratory distress
syndrome. The purpose of this study was to examine our experience with inhaled NO in 10 adult patients
with burn injuries and acute respiratory distress syndrome-related oxygenation failure. The patients had a
mean age of 50 +/- 19 years and a mean burn size of 41% +/- 20% of the total body surface area. Seven
patients died and 3 survived. The survivors and nonsurvivors did not differ with respect to age, burn size,
pre-NO ventilator settings, or indices of oxygenation including PaO2, oxygen saturation in arterial blood,
PaO2/fraction of inspired oxygen (FIO2) ratio, and alveolar-arterial oxygen tension difference. The
concentration of NO administered ranged between 5 ppm and 30 ppm. PaO2, oxygen saturation in arterial
blood, and the PaO2/FIO2 ratio increased in all patients. Although it was not statistically significant,
survivors tended to have a more vigorous and sustained response than non-survivors; this was best
exemplified by the change in PFR. During the first hour of therapy, the PaO2/FIO2 ratio increased from
64.3 +/- 12.7 to 231.8 +/- 154.5 in survivors and from 93.9 +/- 44.0 to 161.5 +/- 81.8 in the nonsurvivors.
After 12 hours of therapy, the PaO2/FIO2 ratio was 306.2 +/- 333.7 in the survivors and 178.9 +/- 69.9 in
the nonsurvivors. There were no complications associated with the use of inhaled NO. Although a
stronger early response to NO seems to occur in survivors, we cannot definitely conclude that the early
response pattern is predictive of recovery. Nonetheless, we believe that inhaled NO has a useful role in
the treatment of patients with burn injuries and severe acute respiratory distress syndrome-related
oxygenation failure
Dellinger RP, Zimmerman JL, Taylor RW, et al, for the Inhaled Nitric Oxide in ARDS Study Group.
Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a
randomized phase II trial. Crit Care Med. 1998;26:15–23
Sheridan, , Massachusetts General Hospital and Shriners Burns Institute-Boston Unit, and Departments
of Surgery and Anesthesia ,arvard Medical School, Boston, Massachusetts. Inhaled Nitric Oxide in Burn
Patients with Respiratory Failure. ournal of Trauma-Injury Infection & Critical Care. 42(4):629-634,1997.
Inhaled nitric oxide (NO) has the potential to improve ventilation/perfusion matching and decrease
pulmonary artery pressure in patients with profound respiratory failure.
Methods: Eight patients, average age of 35 years (range, 2.5-77 years) and burn size 49% (range, 1980%), with inhalation injury and respiratory failure failing conventional management (average Pao2
28
/FIO2 ratio (PFR) 85) were given inhaled NO at 20 ppm.
Results: An immediate mean increase in PFR of 10% and a decrease in pulmonary artery mean pressure
of 7.8% was noted. At 24 hours, the average improvement in PFR was 28% and that in pulmonary artery
mean pressure was 7.7%. Although not reaching statistical significance, these changes were more
pronounced in those patients who went on to survive. There was no hypotension attributed to NO
administration, and maximum methemoglobin levels averaged 0.9%.
Conclusions: Inhaled NO can be safely administered to selected burn patients with severe respiratory
failure who are perceived to be failing conventional support. Although current data are not adequate to
support its general use, an immediate and sustained improvement in PFR and pulmonary artery mean
pressure may correlate with eventual recovery of pulmonary function. Continued evaluation in controlled
settings seems warranted and is in progress.
Heparina inhalada
Murakami,., High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep.
Clin Sci (Lond) 104 (2003), pp. 349–356.
Murakami, . Heparin Nebulization Attenuates Acute Lung Injury in Sepsis Following Smoke Inhalation
in Sheep. Shock. 18(3):236-241, September 2002.
Murakami. Recombinant antithrombin attenuates pulmonary inflammation following smoke inhalation
and pneumonia in sheep. Crit Care Med. 2003 Feb;31(2):577-83.
Bone. Effects of manganese superoxide dismutase, when given after inhalation injury has been
established. Crit Care Med. 2002 Apr;30(4):856-60.
Tasaki., Effects of heparin and lisofylline on pulmonary function after smoke inhalation injury in an
ovine model. Crit Care Med 30 (2002), pp. 637–643. Tasaki. (volver)
Objective : This study evaluates the effects of heparin alone and in combination with lisofylline, 1-(5-Rhydroxyhexyl)3,7-dimethylxanthine, on severe smoke injury.Design : Prospective animal study.
Subjects : Eighteen 1-yr-old female sheep, weighing 24–32 kg.
Conclusion : Treatment with heparin alone did not attenuate pulmonary dysfunction after severe smoke
injury. Combined treatment with nebulized heparin and systemic lisofylline had beneficial effects on
pulmonary function in association with a decrease in blood flow to poorly ventilated areas and less lipid
peroxidation….. Comentario en editorial de ..
Sheridan R: Specific therapies for inhalation injury. Crit Care Med 2002; 30: 718–719. At present, there
are no specific therapies for inhalation injury. Treatment is supportive only and consists of intubation for
standard indications, positive pressure ventilation, pulmonary toilet, and antibiotics for established
infection. There is no value to prophylactic intubation, steroids, or antibiotics (6). In practical terms, one
can only support such patients while they go through a predictable 7- to 21-day period of endobronchial
slough, secondary failure of gas exchange and compliance, infection, and healing. Survivors are left with
a variable degree of permanent lung dysfunction (7). Presently, optimal care of patients with inhalation
injury consists of support that avoids ventilator-induced lung injury (8, 9).
Consequently, it’s exciting to see work such as that of Dr. Tasaki and colleagues (10), in this issue of
Critical Care Medicine, which attempts to actually influence the natural history of the disease process.
This group evaluated the impact of nebulized heparin and nebulized heparin plus intravenous lisofylline
(compared with a nebulized saline control) on the first 48 hrs of inhalation injury in sheep. Nebulized
heparin has been theorized to decrease endobronchial cast formation (11). Intravenous lisofylline is
converted to pentoxifylline in the liver and is reported to inhibit the production of inflammatory
mediators, down-regulate leukocyte activation, and suppress formation of classes of lymphocytes thought
to be involved in the physiology of inhalation injury (12). Earlier work with nebulized heparin showed
mixed results in animals (11) and suggested benefit in humans when compared with historic controls (13).
The authors allude to their own unpublished work in a similar model of inhalation injury that
demonstrated no benefit to lisofylline alone, although it would have been interesting to have included this
arm in the current work. They found that the combination of intravenous lisofylline and nebulized heparin
attenuated the increase in alveolar-arterial oxygen gradient and shunt fraction at 48 hrs and reduced the
requirement for positive pressure to achieve oxygenation and ventilation targets (10). Heparin alone was
of no value, although a modest benefit might have been obscured by the small numbers of animals
studied.
This work is important, in that it represents an effort to influence the natural history of inhalation injury,
not just provide less injurious support. It would have been valuable to continue the experiment for >48
hrs, because the clinical course of inhalation injury usually occurs over many days. This time course may
29
explain the absence of histologic differences between the study and control groups. However, overt
problems often are encountered within the first 48 hrs in severe inhalation injury, making the authors’
conclusions interesting. As clearly noted by the authors, this therapy is not without potential
complications, including greater fluid requirements to maintain a euvolemic state, reduced serum protein
concentration, and copious endobronchial secretions (previously reported with heparin treatment). The
authors suggest that further work is required before this therapy can be recommended for clinical practice.
The complexity of the pathophysiology of inhalation injury makes it clear that there will be no simple
solution. However, pioneering work such as that of Dr. Tasaki and colleagues (10) anticipates a time
when we may be able to influence the course of inhalation injury.
Desai, Reduction in mortality in pediatric patients with inhalation injury with aerosolized
heparin/acetylcystine therapy. J Burn Care Rehabil 19 (1998), pp. 210–212. (volver)
Smoke-inhalation injury causes a destruction of the ciliated epithelium that lines the tracheobronchial
tree. Casts produced from these cells, polymorphonuclear leukocytes and mucus, can cause upper-airway
obstruction, contributing to pulmonary failure. We have reported that a combination of aerosolized
heparin and a mucolytic agent, acetylcystine, can ameliorate cast formation and reduce pulmonary failure
secondary to smoke inhalation. In this study, 90 consecutive pediatric patients between 1985 and 1995
who had bronchoscopically diagnosed inhalation injury requiring ventilatory support were studied. Fortythree children admitted between 1985 and 1989 acted as controls. Forty-seven children admitted between
1990 and 1994 received 5000 units of heparin and 3 ml of a 20% solution of acetylcystine aerosolized
every 4 hours the first 7 days after the injury. All patients were extubated when they were able to
maintain spontaneously a PaO2/FIO2 ratio of more than 400. The number of patients requiring
reintubation for successive pulmonary failure was recorded, as was mortality. The results indicate a
significant decrease in reintubation rates, in incidence of atelectasis, and in mortality for patients treated
with the regimen of heparin and acetylcystine when compared with controls. Heparin/acetylcystine
nebulization in children with massive burn injury and smoke-inhalation injury results in a significant
decrease in incidence of reintubation for progressive pulmonary failure and a reduction in mortality
Enkhbaatar, Herndon D. Aerosolized tissue plasminogen inhibitor improves pulmonary function in
sheep with burn and smoke inhalation. Shock. 2004 Jul;22(1):70-5. Department of Anesthesiology,
University of Texas Medical Branch, Galveston,
Acute respiratory distress syndrome is a major complication in patients with thermal injury. The
obstruction of the airway by cast material, composed in part of fibrin, contributes to deterioration of
pulmonary gas exchange. We tested the effect of aerosol administration of tissue plasminogen activator,
which lyses fibrin clots, on acute lung injury in sheep that had undergone combined burn/smoke
inhalation injury. Anesthetized sheep were given a 40% total body surface, third degree burn and were
insufflated with cotton smoke. Tissue plasminogen activator (TPA) was nebulized every 4 h at 1 or 2 mg
for each nebulization, beginning 4 h after injury. Injured but untreated control sheep developed multiple
symptoms of acute respiratory distress syndrome: decreased pulmonary gas exchange, increased
pulmonary edema, and extensive airway obstruction. These control animals also showed increased
pulmonary transvascular fluid flux and increased airway pressures. These variables were all stable in
sham animals. Nebulization of saline or 1 mg of TPA only slightly improved measures of pulmonary
function. Treatment of injured sheep with 2 mg of TPA attenuated all the pulmonary abnormalities noted
above. The results provide evidence that clearance of airway obstructive cast material is crucial in
managing acute respiratory distress syndrome resulting from combined burn and smoke inhalation injury.
Thompson. Successful Management of Adult Smoke Inhalation with Extracorporeal Membrane
Oxygenation.J Burn Care Rehabil. 2005 January/February;26(1):62-66.
Maybauer. Effects of manganese superoxide dismutase nebulization on pulmonary function in an ovine
model of acute lung injury.
Shock. 2005 Feb;23(2):138-143.
30
► Intoxicación por CO y Cianidas
Mueller, Hydroxycobalamine (Vitamin B12) as Therapy in Burn Victims. Relative Binding to Cyanide,
Nitric Oxide, and Carbon Monoxide. ASA Annual Meeting Abstracts. CRITICAL CARE. 99(3A):A400,
October 2003.
Abelsohn. Carbon Monoxide Poisoning. CMAJ.1666 (13): 1685-1690. 2002
Sauer, Hydroxocobalamin: Improved public health readiness for cyanide disasters. Annals of
Emergency Medicine. 37(6):635-641, June 2001. Sauer . (volver)
The United States is under the constant threat of a mass casualty cyanide disaster from industrial
accidents, hazardous material transportation incidents, and deliberate terrorist attacks. The current
readiness for cyanide disaster by the emergency medical system in the United States is abysmal. We, as a
nation, are simply not prepared for a significant cyanide-related event. The standard of care for cyanide
intoxication is the cyanide antidote kit, which is based on the use of nitrites to induce
methemoglobinemia. This kit is both expensive and ill suited for out-of-hospital use. It also has its own
inherent toxicity that prevents rapid administration. Furthermore, our hospitals frequently fail to stock this
life-saving antidote or decline to stock more than one. Hydroxocobalamin is well recognized as an
efficacious, safe, and easily administered cyanide antidote. Because of its extremely low adverse effect
profile, it is ideal for out-of-hospital use in suspected cyanide intoxication. To effectively prepare for a
cyanide disaster, the United States must investigate, adopt, manufacture, and stockpile hydroxocobalamin
to prevent needless morbidity and mortality. [Sauer SW, Keim ME. Hydroxocobalamin: improved public
health readiness for cyanide disasters. Ann Emerg Med. June 2001;37:635-641.]
For years, the well-known Cyanide Antidote Kit (CAK; Lilly) has been the only commercially available
antidote approved by the US Food and Drug Administration (FDA) for treatment of cyanide poisoning in
the United States. Lilly has discontinued its production. Today, the CAK is available from one source,
Taylor Pharmaceuticals (formerly Pasadena Research Laboratories).
Hydroxocobalamin has been recognized as an antidote for cyanide toxicity for more than 40 years. 29-31
It is in active use in France as an antidote for cyanide intoxication. Excellent data about its efficacy,
safety, and adverse reactions are available. Hydroxocobalamin (vitamin B12a) is a precursor molecule of
cyanocobalamin (vitamin B12) and is currently approved by the FDA. It is the drug of choice for the
treatment of pernicious anemia, and several hundred thousand doses are administrated annually. Vitamin
B12a is available over the counter as a food supplement, which is taken by millions of people without
reported harm. However, hydroxocobalamin is rarely used in the United States as a cyanide antidote. 32
Hydroxocobalamin binds with cyanide on an equimolar basis to form cyanocobalamin (vitamin B12) and
thereby detoxify cyanide. It appears that 5 g of the antidote will effectively treat patients intoxicated with
up to 40 µmol/L without the need for an additional dose.
CYANOKIT 2 VLS.
2,5gr.
25-01-2001
Urgencias/U.C.E.
416.00 € *
ORPHAN
EUROPE
HIDROXICOBALAMINA
(Vit.B12)
(Cyanokit® vial 2,5 g)
HIDROXICOBALAMINA
Intoxicación por humo en que se sospeche
contenido en cianuros (ej. humos
(volver)
Juurlink. Hyperbaric oxygen for carbon monoxide poisoning (Cochrane Review). In: The Cochrane
Library, Issue 4, 2004. Chichester, UK: John Wiley & Sons, Ltd.
Objectives: To assess the effectiveness of hyperbaric oxygen (HBO) compared to normobaric oxygen
(NBO) for the prevention of neurologic symptoms in patients with acute carbon monoxide poisoning.
Main results: Six randomized controlled trials were identified. The trials were of varying quality. Three
trials employing different doses of NBO and HBO were included in the primary analysis. The severity of
CO poisoning was inconsistent between trials. At one month follow-up after treatment, symptoms
possibly related to carbon monoxide poisoning were present in 81 of 237 patients (34.2%) treated with
HBO, compared with 81 of 218 patients (37.2%) treated with NBO (O.R. for benefit with HBO 0.82;
95% CI 0.41-1.66).
Reviewers' conclusions: There is no evidence that unselected use of HBO in the treatment of acute CO
poisoning reduces the frequency of neurological symptoms at one month. However, evidence from the
available randomized controlled trials is insufficient to provide clear guidelines for practice. Further
research is needed to better define the role of HBO, if any, in the treatment of carbon monoxide
31
poisoning. This research question is ideally suited to a multicentre, randomized, double-blind controlled
trial.
Weaver, Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 347 (2002), pp. 1057–
1067.
Background: Patients with acute carbon monoxide poisoning commonly have cognitive sequelae. We
conducted a double-blind, randomized trial to evaluate the effect of hyperbaric-oxygen treatment on such
cognitive sequelae. Methods: We randomly assigned patients with symptomatic acute carbon monoxide
poisoning in equal proportions to three chamber sessions within a 24-hour period, consisting of either
three hyperbaric-oxygen treatments or one normobaric-oxygen treatment plus two sessions of exposure to
normobaric room air. Oxygen treatments were administered from a high-flow reservoir through a face
mask that prevented rebreathing or by endotracheal tube. Neuropsychological tests were administered
immediately after chamber sessions 1 and 3, and 2 weeks, 6 weeks, 6 months, and 12 months after
enrollment. The primary outcome was cognitive sequelae six weeks after carbon monoxide poisoning.
Results: The trial was stopped after the third of four scheduled interim analyses, at which point there were
76 patients in each group. Cognitive sequelae at six weeks were less frequent in the hyperbaric-oxygen
group (19 of 76 [25.0 percent]) than in the normobaric-oxygen group (35 of 76 [46.1 percent], P=0.007),
even after adjustment for cerebellar dysfunction and for stratification variables (adjusted odds ratio, 0.45
[95 percent confidence interval, 0.22 to 0.92]; P=0.03). The presence of cerebellar dysfunction before
treatment was associated with the occurrence of cognitive sequelae (odds ratio, 5.71 [95 percent
confidence interval, 1.69 to 19.31]; P=0.005) and was more frequent in the normobaric-oxygen group (15
percent vs. 4 percent, P=0.03). Cognitive sequelae were less frequent in the hyperbaric-oxygen group at
12 months, according to the intention-to-treat analysis (P=0.04). Conclusions: Three hyperbaric-oxygen
treatments within a 24-hour period appeared to reduce the risk of cognitive sequelae 6 weeks and 12
months after acute carbon monoxide poisoning. Copyright © 2002 Massachusetts Medical Society.
Scheinkestel, Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised
controlled clinical trial [see comments] . Med J Aust 170 (1999), pp. 203–210.
Objective: To assess neurological sequelae in patients with all grades of carbon monoxide (CO) poisoning
after treatment with hyperbaric oxygen (HBO) and normobaric oxygen (NBO). Design: Randomised
controlled double-blind trial, including an extended series of neuropsychological tests and sham
treatments in a multiplace hyperbaric chamber for patients treated with NBO. Setting: The multiplace
hyperbaric chamber at the Alfred Hospital, a university-attached quarternary referral centre in Melbourne
providing the only hyperbaric service in the State of Victoria. Patients: All patients referred with CO
poisoning between 1 September 1993 and 30 December 1995, irrespective of severity of poisoning.
Pregnant women, children, burns victims and those refusing consent were excluded. Intervention: Daily
100-minute treatments with 100% oxygen in a hyperbaric chamber - 60 minutes at 2.8 atmospheres
absolute for the HBO group and at 1.0 atmosphere absolute for the NBO group - for three days (or for six
days for patients who were clinically abnormal or had poor neuropsychological outcome after three
treatments). Both groups received continuous high flow oxygen between treatments. Main outcome
measures: Neuropsychological performance at completion of treatment, and at one month where possible.
Results: More patients in the HBO group required additional treatments (28% v. 15%, P = 0.01 for all
patients; 35% v. 13%, P = 0.001 for severely poisoned patients). HBO patients had a worse outcome in
the learning test at completion of treatment (P = 0.01 for all patients; P = 0.005 for severely poisoned
patients) and a greater number of abnormal test results at completion of treatment (P = 0.02 for all
patients; P = 0.008 for severely poisoned patients). A greater percentage of severely poisoned patients in
the HBO group had a poor outcome at completion of treatment (P = 0.03). Delayed neurological sequelae
were restricted to HBO patients (P = 0.03). No outcome measure was worse in the NBO group.
Conclusion: In this trial, in which both groups received high doses of oxygen, HBO therapy did not
benefit, and may have worsened, the outcome. We cannot recommend its use in CO poisoning
Saffle 2003. Therapies for inhalation injury
Previously, pretreatment of experimental animals with manganese superoxide dismutase has markedly
reduced the hypoxic and hypotensive effects of inhalation injury. The efficacy of this treatment after
inhalation injury was evaluated by Bone and associates.[46] Ewes given inhalation injuries were
randomized to receive various doses of manganese superoxide dismutase one hour after injury. No major
differences were observed between control animals and those given three different doses of manganese
superoxide dismutase (1,000, 3,000, or 9,000 units) in cardiac output, pulmonary artery pressure,
32
pulmonary vascular resistance, or lung lymph flow. Bone and associates [46] concluded that this therapy
is substantially less effective than pretreatment.
Tasaki and coauthors[47] evaluated the effectiveness of aerosolized heparin with and without the
addition of intravenous lisofylline, which inhibits a number of inflammatory mediators, in a sheep model
of inhalation injury. Only animals treated with both heparin and lisofylline demonstrated notable
improvements in alveolar-arterial oxygen gradient and shunt fraction, and a reduced need for ventilator
support. This study questions earlier studies demonstrating improvements in clinical parameters of
pulmonary function after treatment with either aerosolized or intravenous heparin alone.
S. Compartimental Abdominal
Hobson : Release of abdominal compartment syndrome improves survival in patients with burn injury. J
Trauma 2002;53:1129. Hobson. (volver)
Background : Abdominal compartment syndrome (ACS) has rarely been described as a complication of
burn injury. This study describes cases of ACS in patients with burn injury and the physiologic results of
abdominal release. Two studies of ACS resulting from severe burn injuries have been published to date.
6,7 Together, these two studies include 40 patients with burn injuries. Diagnosis of compartment
syndrome was first ascertained by clinical impression. ACS was suspected in any patient who presented
with a clinically tense abdomen in combination with either exceedingly high peak inspiratory pressures
that compromised the ability to ventilate the patient, or oliguria despite aggressive fluid resuscitation.
Clinical suspicion was then supported by assessing intra-abdominal pressure. Intra-abdominal pressure
was estimated by measuring bladder pressure, in the manner described by Kron et al. 5 and validated in a
study by Iberti et al., 8 in which 30 to 50 mL of sterile saline is injected into the urinary bladder through
an indwelling Foley catheter. Injected fluid is then allowed to flow out of the bladder until a constant
column of water fills the catheter tubing with no interfering air. The catheter is subsequently clamped
immediately distal to an aspiration port. An 18-gauge needle is inserted into the aspiration port and
connected to a pressure transducer, which is the same type of system used for arterial line pressure
monitoring and which is readily available in the ICU setting. The transducer is then normalized to zero at
the level of the pubic symphysis, and the bladder pressure is transduced.
Methods : Charts for all patients admitted to two major burn center intensive care units from January
1998 through August 2000 were reviewed for ACS. Physiologic parameters were compared before and
after abdominal release.
Results : Ten of 1,014 patients developed ACS. Abdominal release improved peak inspiratory pressures
and Acute Physiology and Chronic Health Evaluation II scores (p < 0.03). The amount of fluid required
to maintain adequate urine output also decreased substantially. Forty percent of patients with ACS
survived to discharge.
Conclusion : Abdominal release for patients with ACS and severe burn injury results in physiologic
improvement and a 40% survival rate. We recommend bladder pressure monitoring for all patients with
severe burn injuries and abdominal decompression in any patient who develops pressures greater than 30
mm Hg if they have signs of physiologic compromise. Aggressive expectant management can effect a
40% survival rate in this group of severely injured patients
Trombosis venosa
Wibbenmeyer : The prevalence of venous thromboembolism of the lower extremity among thermally
injured patients determined by duplex sonography. J Trauma 2003;55:1162. Wibbenmeyer. (volver)
We prospectively studied 148 thermally injured patients with hospital stays of greater than 3 days with
lower extremity duplex ultrasonograms obtained at admission and discharge.
Results : Nine patients experienced VTE (6.08%). Eight of the nine deep venous thromboses were
proximal. One of the two pulmonary embolisms was fatal. Treatment risk factors that were associated
with VTE were the presence of a central venous line (p = 0.020) and transfusion of more than 4 units of
packed red blood cells (p = 0.023). These treatment factors were significantly related to each other (p <
0.0001), to body surface area burned, and to intervention.
Conclusion : The prevalence of VTE in burn patients is similar to that of moderate- to high-risk general
surgical patients for whom VTE prophylaxis is recommended. VTE prophylaxis of burn patients,
especially those requiring central venous lines and more than 4 units of packed red blood cells, should be
considered
33
Saliba. Heparin in the treatment of burns: a review • Burns, Volume 27, Issue 4, 1 June 2001, Pages 349358.
Saliba
(volver)
Saffle. What’s new in general surgery: burns and metabolism. Journal of the American College of
Surgeons, Volume 196, Issue 2, February 2003, Pages 267-289. Saffle
(volver)
Deep venous thrombosis in burn patients
Although prospective surveillance studies have demonstrated that trauma patients have a high incidence
of deep venous thrombosis (DVT) and pulmonary embolism (PE), limited data suggest that burn patients
are at low risk. Recently published practice guidelines for burn patients did not find evidence to
recommend routine prophylaxis against DVT, although burn patients theoretically have many of the same
risk factors for DVT (tissue injury, hypercoaguability, bed rest, etc) as trauma victims. In a small
prospective study from Michigan, Wahl and colleagues[32] found DVT/PE in 11 of 30 burn patients
(23%) followed with weekly duplex ultrasonographic examinations. This intriguing finding should be
evaluated further in a large, multicenter study. Because clinically significant DVT/PE seems to be
uncommon in burn patients, such a study would, ideally, also be able to define the therapeutic
implications of asymptomatic DVT found on duplex examination in this population.
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