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cerebral-resucitacion

Resucitación cerebral y pronóstico de la RCP

1. Introducción

La resucitación cardiopulmonar (RCP) puede restaurar la circulación espontánea hasta en un 50% de los pacientes que sufren una parada cardiaca. Sin embargo, la mayoría de esos pacientes mueren durante el periodo post-resucitación, y esa mortalidad en gran parte es debida a daño neuronal después de isquemia cerebral global (1).

De los supervivientes hasta un 50 % de los pacientes quedan con afectación de sus funciones cognitivas.

Los conceptos de resucitación cerebral y pronóstico de la RCP están íntimamente unidos, pues el pronóstico neurológico condiciona la evolución del paciente que sobrevive a la parada cardiaca atendida extra o intra hospitalariamente.

La resucitación cerebral implica tener en cuenta que el cerebro condiciona el pronóstico en todas las fases de la atención a la parada cardiaca.

El pronóstico de la RCP es fundamentalmente neurológico, siendo esenciales las pruebas neurológicas como ayuda al clínico para prever la evolución del paciente que ha sobrevivido en primera instancia a la parada.

 

2. Resucitación Cerebral

2.1. ¿Qué significa Resucitación Cerebral?
Resucitación cerebral es un concepto introducido por Peter Safar el padre de la RCP tal y como la conocemos hoy en día.

Su hija de 11 años murió tras ser reanimada por un status asmático y, aunque las maniobras de RCP fueron efectivas, su pronóstico neurológico fue infausto, falleciendo meses después. Desde entonces Peter Safar y sus discípulos enfocaron sus investigaciones hacia la protección del cerebro durante la RCP y después en los cuidados postRCP. Muchos de los conceptos derivados de las investigaciones de los grupos interesados en la Resucitación cerebral se han incorporado a las recomendaciones internacionales de la RCP no sin lentitud, llegando a un concepto llamado resucitación cardiocerebral (RCC), cuyos pilares son asegurar la perfusión cerebral durante la parada cardiaca y proteger al cerebro de lesiones secundarias durante las primeras 24-48 horas postRCP (2).

La RCC es un protocolo de soporte vital extracerebral orientado al cerebro y se considera mejor que la resucitación cardiopulmonar sin más.

Parafraseando a Peter Safar: si hay una terapia no tóxica que pueda mejorar el pronóstico neurológico postRCP, esta debe ser considerada.

2.2. Resucitación cerebral durante la RCP
El concepto de RCC se basa en la opinión fundada de que la resucitación, sobre todo la extrahospitalaria, está lejos de ser óptima y que el mantenimiento de la perfusión cerebral durante la RCP es crítico para la función neuronal postRCP. Gracias a los estudios basados en este concepto, varias de sus ideas han sido y están siendo incorporadas a los algoritmos internacionales de RCP.

El grupo de Arizona, el más activo en este tema, describe tres fases en la resucitación cardiocerebral:

  • 1º fase eléctrica: En los pacientes que debutan con Fibrilación ventricular (FV), los 5 primeros minutos. En esta fase lo más importante es desfibrilar (de ahí la importancia de la disponibilidad extrahospitalaria de desfibriladores automáticos). Más de un choque seguido no protege el cerebro ya que retrasa y disminuye la administración de las compresiones torácicas.
  • 2º fase Hemodinámica: Los siguientes 5-15 minutos después de la fase eléctrica. Lo más importante en esta fase es generar perfusión cerebral y coronaria.
  • 3º Fase metabólica: Después de las anteriores dos fases. En esta fase es donde adquieren protagonismo acciones como la hipotermia y otras.

El masaje cardiaco, su indicación, momento, frecuencia e intensidad son el pilar de la resucitación cerebral durante la RCP.

El grupo de Arizona observó que los testigos de RCP extrahospitalaria tenían precaución en iniciar las maniobras de resucitación y preferían llamar a los servicios de emergencia por su reticencia en realizar el boca a boca, por lo que no iniciaban RCP con masaje cardiaco. Teniendo en cuenta la teoría de la resucitación cerebral, se investigó por este grupo y otros la RCP solo con masaje cardiaco externo y sin ventilación en la parada extrahospitalaria, y se observó una supervivencia incluso superior a la RCP convencional. La clave para la supervivencia y para disminuir los problemas neurológicos es la administración precoz y continuada del masaje cardiaco, asegurando en la medida de lo posible la perfusión cerebral y coronaria (3).

La recomendación para la resucitación cerebral es 200 compresiones antes de analizar el ritmo y desfibrilar, 200 más posterior al choque, y otras 200 antes de analizar el ritmo de nuevo. El ritmo de las compresiones debe ser de 100-120 por minuto y con una profundidad de 5 cm (en el adulto).

Aun así, en las mejores circunstancias es difícil conseguir con el masaje cardiaco al menos un 30% del gasto cardiaco (GC) normal, por eso la importancia de realizarlo de forma adecuada y pensando en forma de resucitación cerebral.

De hecho se considera una reanimación de alta calidad si (4):

  • Se minimizan las interrupciones de las compresiones torácicas (> 80 % del tiempo de la RCP dedicado a las compresiones )
  • Frecuencia de las compresiones entre 100-120 min
  • Profundidad de las compresiones hasta 5 cm
  • Evitar excesiva ventilación

La fracción de compresiones torácicas es la proporción del tiempo que las compresiones son hechas respecto al total del tiempo de la RCP (Tiempo realizando compresiones / Tiempo total RCP).

Las interrupciones de las compresiones torácicas disminuyen el flujo sanguíneo y el transporte de oxígeno al cerebro y a las coronarias y reduce las oportunidades de conseguir una recuperación del ritmo espontáneo (Return of Spotaneus Circulation, ROSC) y de preservar una función neurológica intacta al alta hospitalaria. Se han realizado estudios donde se observó que la supervivencia y el resultado neurológico se relacionan directamente con la fracción de compresiones torácicas (5, 6).

El objetivo debe ser del 80% de fracción de compresiones torácicas tanto en la intrahospitalaria como en la extrahospitalaria.

Hay estrategias recomendadas para minimizar las pausas en las compresiones pre choque eléctrico como son entre otras: mantenimiento de las compresiones torácicas mientras se cargan las palas, usar dispositivos supraglóticos en vez de realizar intubación, y si se decide intubar, continuar las compresiones mientras se intuba.

Una alternativa a las compresiones manuales son los dispositivos mecánicos, como el LUCASTM (Lund University Cardiac Arrest System), y el Autopulse®, pero aún está por determinar su superioridad a las compresiones manuales.

La respiración agónica o gasping puede ser buena ya que proporciona ventilación con presión negativa, pero en ocasiones se malinterpreta ya que puede hacer pensar que no se necesita masaje cardiaco ni RCP, sin embargo la presencia de gasping es indicación de inicio de masaje cardiaco.

Se debe tener en cuenta que la presión positiva disminuye el retorno venoso y empeora la reperfusión cerebral y coronaria. También impide una presión negativa intratorácica en la fase de liberación de las compresiones torácicas.

Si la causa sospechada es respiratoria, se debe abrir la vía aérea y colocar un dispositivo orofaríngeo.

2.3. Resucitación cerebral durante los cuidados postRCP
2.3.1. Síndrome post-reperfusión y cuidados específicos neurológicos
La encefalopatía postanóxica postRCP es multifactorial. El daño cerebral es la causa de muerte en el 68% de los pacientes tras una PCR extrahospitalaria y del 23% de la PCR intrahospitalaria. El 1- 2 % de los pacientes post RCP quedan en un estado vegetativo persistente.

Peter Safar ya describió como la recuperación cerebral después de más de 5 minutos de parada cardiaca estaba obstaculizada por alteraciones secundarias complejas de múltiples órganos después de la reperfusión. Es lo que se conoce como síndrome posreperfusión.

La intensidad y gravedad del síndrome posreperfusión guardan proporción directa con la duración con el tiempo de PCR sin recibir RCP.

Los componentes clave que hay que tratar son:

  1. Persistencia de la enfermedad precipitante (resolver precozmente).
  2. Daño cerebral posparada (principal causa de muerte)
  3. Daño miocárdico posparada (importante aturdimiento miocárdico)
  4. Síndrome de respuesta inflamatoria severa (SRIS): cuadro hemodinámico similar a la sepsis

Las distintas fases del síndrome posreperfusión se basan en los tiempos transcurridos:

  1. Fase inmediata (primeros 20 min tras recuperación de la circulación espontánea, RCE)
  2. Fase precoz (desde los 20 min hasta las 6–12 h)
  • – Las intervenciones precoces podrían ser más efectivas
  1. Fase intermedia (desde las 6–12 h hasta las 72 h)
  • – Los mecanismos de lesión aún permanecen activos y se debe mantener un tratamiento intensivo
  1. Fase de recuperación (a partir de las 72 h)
  • – El pronóstico se hace más fiable y los resultados finales son más predecibles
  1. Fase de rehabilitación (desde el alta hospitalaria hasta lograr la máxima función).

En el síndrome posreperfusión hay fallos y desigualdades de perfusión cerebral, daño por reoxigenación cerebral e intoxicación cerebral por fallos de órganos extracerebrales.

Existe un aporte de oxigeno inadecuado, cascadas metabólicas y autointoxicación producidas por metabolitos generados por la reoxigenación, alteraciones hematológicas (especialmente hipercoagulabilidad), edema cerebral, y alteraciones del sistema inmune.

La cascada de la muerte cerebral comienza rápidamente, a los 5-6 segundos, se pierde la conciencia y en el primer minuto se produce un cese de las funciones del tronco cerebral, respiración agónica y pupilas fijas. A los 4-6 minutos se inicia la depleción de ATP y la acumulación masiva de calcio, con la consiguiente toxicidad celular, necrosis y daño irreversible (7).

El problema añadido es que si se restaura el flujo cerebral la reperfusión no detiene la degeneración neuronal, los radicales libres generados durante la isquemia pueden agravar las lesiones.

Además, una vez restaurado el flujo cerebral pueden quedar áreas hipoperfundidas debido, entre otras razones, a la hipercoagulabilidad. El cerebro tarda 24 h en reperfundirse totalmente, en las zonas hipoperfundidas o sin flujo se produce congestión, edema y pérdida de la autorregulación. En las áreas no perfundidas se produce finalmente una reacción gliótica y una degeneración transináptica.

Las áreas más vulnerables a la isquemia y la hipoperfusión son:

  • – Neocórtex (CA1)
  • – Folium del hipocampo (CA4-6)
  • – Purkinje del cerebelo, putamen, caudado y tálamo

La resucitación cerebral y los cuidados específicos neurológicos están imbricados con los generales, de los que algunos veremos con más detalle más adelante en este capítulo como la hipotermia, el manejo ventilatorio y hemodinámico y el óxido nítrico.

Peter Safar ya apuntaba que solo una RCP de alta calidad y precoz que mantenga una presión de perfusión cerebral optima y unos cuidados posresucitación orientados a mantener esa perfusión, disminuir el metabolismo cerebral, y eliminar sustancias toxicas son lo que mejoran los resultados neurológicos.

El cerebro sobrevive si sobrevive el resto del cuerpo.

Los objetivos terapéuticos básicos son crear un ambiente óptimo para la recuperación con normotensión, normocapnia y normoglucemia (8).

La inestabilidad hemodinámica, la disfunción sistólica y diastólica, la afectación coronaria, la activación de la inflamación y de la coagulación postRCP están íntimamente relacionadas con los acontecimientos en el cerebro.

La disminución del metabolismo mediante sedación profunda, posición de la cabeza neutra y elevada y relajación muscular son medidas básicas de neuroprotección.

También el control de la glucemia, manteniendo niveles de menos de < 150 mg/dL, está recomendado ya que se ha comprobado que la asociación hiperglucemia más isquemia es igual a acidosis láctica y daño cerebral.

La incidencia de las convulsiones tras la PCR oscila entre el 5 y el 20%, pero podría ser mayor. Tras la recuperación del ROSC debe realizarse un EEG lo antes posible y repetirse o monitorizarse de forma continua en los pacientes en coma. El tratamiento de las convulsiones o estatus epiléptico es el mismo que en cualquier otra patología. No se recomienda el uso profiláctico de anticomiciales, aunque algunos grupos partidarios de la resucitación cerebral la recomiendan si no se ha hecho EEG precoz.

Para las mioclonías el tratamiento de elección sería el clonacepam.

2.3.2. Hemodinámica post RCP
La recuperación del ritmo cardiaco espontáneo y ROSC es sólo el primer paso para conseguir la recuperación completa tras una PCR.

No hay un consenso sobre cuáles deben ser los objetivos hemodinámicos, aunque sabemos que:

  • Tienen mejor pronóstico los pacientes que espontáneamente tienen mejor tensión arterial media.
  • El 47,5 % de los pacientes postRCP tienen hipotensión arterial y precisan aminas.
  • El uso de aminas para subir la tensión arterial se asocia a peor pronóstico.

La recomendación es individualizar el shock, buscar su causa y tratar en función de que sea cardiogénico y precise cateterismo o inotrópicos, séptico y precise volumen y aminas, y así con el resto de causas (9).

Se recomienda una monitorización avanzada con monitores de gasto cardiaco y la realización de ecocardiograma.

Hay que recordar que uno de los componentes claves a tratar en el Síndrome Posreperfusión es un SIRS con disminución de la precarga (necesidad de volumen) y, en muchas ocasiones, con necesidad de agentes vasoactivos.

El objetivo general es mantener una tensión arterial media mayor de 70 mmHg.

En caso de síndrome coronario agudo (SCA), insuficiencia cardiaca congestiva o shock cardiogénico mantener cerca de 80 mmHg la TAM. En HTA previa mal controlada, mantener la TAM próxima a 100 mmHg.

No permitir hipotensión (hipoperfusión cerebral), ni hipertensión (reperfusión e hiperemia, con aumento de la presión intracraneal).

Debido a que la enfermedad coronaria es la causa precipitante, en la mayoría de los pacientes con PCR, debe decidirse durante la fase inmediata si el paciente requiere reperfusión miocárdica.

Para ello debemos englobarlo en uno de estos grupos:

  • Grupo 1: PC de causa claramente no cardíaca. (No cateterismo)
  • Grupo 2: PC de causa posible cardíaca isquémica. (Individualizar para cateterismo)
  • Grupo 3: PC de causa probable cardíaca isquémica. (Cateterismo urgente)
  • Grupo 4: PC de causa claramente cardíaca isquémica. (EKG con SCACEST) (Cateterismo urgente)

2.3.3.Oxigenación y ventilación
Mucho oxigeno es malo y poco también.

Valores elevados de PO2 > 300 mmHg se han asociado a malos resultados y también sucede lo mismo con valores bajos, menores de 60 mmHg.

La recomendación es mantener una Po2 entre 100 y 150 mmHg, o una saturación arterial de oxígeno alrededor del 96 %.

Oximetría cerebral: la saturación cerebral regional de oxigeno es una potencial herramienta para la predicción de ROSC y para guiar la eficacia de la RCP. En varios estudios la media de saturación cerebral fue mayor durante la RCP en los que recuperaron la circulación. Ningún paciente con un valor menor a 30 % consiguió recuperar ROSC. Puede tener un papel en predecir complicaciones neurológicas, y para establecer objetivos durante la RCP que puedan disminuir dichas complicaciones (10). El uso de dispositivos mecánicos para las compresiones se ha asociado a mejor perfusión cerebral.

La hiperventilación puede agravar la isquemia por hipocapnia y vasoconstricción, y la hipoventilación puede producir hipercapnia y aumento de la presión intracraneal, por lo que ambas situaciones se deben evitar manteniendo una PCO2 entre 36 y 42 mmHg. La capnografía es un valioso monitor durante y postRCP (9).

La presión positiva disminuye el retorno venoso y empeora la reperfusión cerebral y coronaria e impide una presión negativa intratorácica en la fase de de liberación de las compresiones torácicas.

Hay una relación inversamente proporcional entre la presión intratorácica y supervivencia, por lo que se deben intentar evitar presiones plateau (Ppl) elevadas.

2.3.4. Óxido nítrico
El óxido nítrico inhalado puede mejorar la supervivencia después de RCP por su efecto neuroprotector.

Aunque los estudios publicados son en animales, su uso está iniciándose en humanos.

Los estudios publicados asocian el óxido nítrico a otras medidas como la hipotermia.

Se observó que los animales que eran deficientes en producción de óxido nítrico tenían muchas más probabilidades de morir después de la reanimación cardiopulmonar Muchos de los pacientes “candidatos” a sufrir parada cardiaca, tienen problemas cardiovasculares como hipertensión, enfermedad arterial periférica, accidentes isquémicos y enfermedad coronaria, que se asocian con la incapacidad de generar óxido nítrico.

En los experimentos animales era especialmente sinérgica la suma de la hipotermia más el óxido nítrico inhalado en la mejoría de la supervivencia después de la reanimación cardiopulmonar

El óxido nítrico inhalado tiene una gran ventana terapéutica en estos pacientes. Se ha estudiado que la ventana de oportunidad se situaría hasta un máximo de 6 horas después de la parada para iniciar la terapia. Su administración recomendada sería inhalado, 40 ppm durante 23 horas (11,12).

2.3.5. Futuras direcciones

  • – Terapia trombolítica/heparina: mejoran la microcirculación; la causa en más de un 50 % de las paradas es infarto de miocardio o embolismo pulmonar; algunos grupos recomiendan en todas las paradas el uso de trombolíticos a dosis bajas si no hay contraindicación, ya que los fenómenos de coagulación están envueltos en los fenómenos de no flujo que empeoran la circulación cerebral postRCP. La parada lleva a una activación de la coagulación y microémbolos sin la correcta fibrinolisis.
  • – Infusiones hipertónicas para restaurar el flujo circulatorio.
  • – Inhibidores de la apoptosis.
  • – Factores de crecimiento.
  • – Eritropoyetina: produce mejoría cardiológica, pero no está claro que sea neuroprotectiva. La dosis usada es de 90.000 unidades durante la RCP.
  • – Inhalación de xenón y argón.
  • – Superóxido dismutasa, alopurinol.

La resucitación cerebral es la vanguardia de la resucitación de la parada cardiaca (13), los nuevos avances y directrices internacionales cada vez van más en la dirección marcada en su día por Peter Safar, lo próximo será la animación suspendida (ralentización o desaceleración de los procesos vitales por medios externos sin llegar a la muerte).

2.4. Hipotermia terapéutica postparada cardiorrespiratoria
El daño neurológico es la causa más común de muerte en pacientes que sufren parada cardiorrespiratoria (PCR) extrahospitalaria y contribuye a la mortalidad de pacientes con PCR intrahospitalaria (14). Se ha visto que el riesgo de mortalidad aumenta por cada grado de temperatura por encima de 37ºC durante las primeras 48 horas postparada (15).

Los datos disponibles actualmente sugieren que el control de la temperatura del paciente que ha sobrevivido a una PCR con un objetivo entre 32 y 36ºC, seguido de evitar la aparición de fiebre, es la estrategia óptima para mejorar la supervivencia.

A partir de aquí se deben diferenciar dos estrategias:

  • Control de temperatura: donde se mantiene la temperatura central del paciente por debajo de los 36ºC
  • Hipertermia terapéutica (TH): Mantener la temperatura central en un rango de 32 a 34ºC

2.4.1. Indicaciones y contraindicaciones
La prevención de fiebre está indicada en todos los pacientes que sobreviven a una PCR sin existir condiciones que proscriban esta intervención (16).

Con respecto a la HT está indicada en los pacientes que tras la recuperación de la circulación espontánea (RCE) no sean capaces de obedecer órdenes sencillas o realizar movimientos intencionales (aquellos movimientos destinados a realizar una acción específica y que no se producen de forma aleatoria).

La única contraindicación absoluta de la HT es la existencia de directivas avanzadas que proscriban cuidados agresivos (por ejemplo últimas voluntades).

No debe realizarse HT en pacientes con sangrado activo no compresible. En mujeres embarazadas (17), inestabilidad hemodinámica, o pacientes en terapia con agentes trombolíticos es posible realizar HT teniendo en cuenta un incremento del riesgo de sangrado en este último grupo (18).

2.4.2. Inicio y duración de la terapia
Se recomienda el inicio de la HT lo antes posible, y aunque no existen gran cantidad de estudios que respalden el tiempo de hipotermia, la mayoría de los autores coinciden en que sea de 48 horas (19).

Aunque no existen datos en humanos, hay estudios en animales donde se ha observado mayor beneficio de la HT cuando se realiza antes o justo al recuperar la circulación espontánea (20).

2.4.3. Objetivos de temperatura
En el caso de pacientes con coma moderado (alguna respuesta motora) y que no tengan lesiones neurológicas importantes como edema cerebral (valorado mediante TC) o patrones malignos en el EEG, se sugiere mantener la temperatura por debajo de 36º por 24 horas.

En pacientes con coma profundo (sin respuestas motoras o ausencia de reflejos del tronco cerebral), con patrón epileptiforme en el EEG o con cambios en el TC que sugieran edema cerebral se sugiere mantener temperaturas de 33ºC por 24-48 horas

2.4.4. Métodos de enfriamiento
Se deben usar los métodos de enfriamiento según la disponibilidad y la experiencia del equipo de cuidados críticos.

Una pauta habitual es el uso de 30 ml/kg de suero fisiológico 0,9% frío (4ºC) administrado de forma rápida mediante sistema de presión que es capaz de reducir la temperatura más de 2ºC a la hora (21). 1 litro de suero fisiológico 0,9% frío administrado en 15 minutos disminuye la temperatura central aproximadamente 1ºC. Se debe tener precaución en pacientes con historia de insuficiencia cardiaca para evitar la sobrecarga hídrica. Se pueden usar además dispositivos externos como mantas de frío y bolsas de hielo aplicadas cerca de los vasos de gran calibre (axila, ingles, cuello). La combinación de sueroterapia fría más medidas externas es la utilizada en muchos centros.

No existe evidencia de superioridad al comparar métodos intravasculares y externos (22).

Los dispositivos termostáticos automáticos aunque no han demostrado ser superiores para alcanzar las temperaturas objetivo, si proveen un control y mantenimiento de temperatura más estable (23).

2.4.5. Sedación y supresión de tiritona
La tiritona (escalofríos o temblores) producidos por la HT tienden a aumentar la temperatura corporal retrasando el alcance de la temperatura objetivo, por lo cual deben evitarse. Es por esto que las pautas habituales de sedación en estos pacientes no son efectivas debiendo titular la dosis de los fármacos sedantes hasta obtener la desaparición de la tiritona.

La selección de los fármacos se debe realizar considerando que el uso de fármacos que tienden a acumularse como el midazolam puede provocar sedación prolongada debido a que la hipotermia disminuye el metabolismo. Esto además disminuye la capacidad de realizar evaluaciones neurológicas frecuentes para vigilar la evolución. Una pauta común es el uso de propofol y fentanilo en perfusión continua.

En ciertas ocasiones es necesario el uso de relajantes musculares para lograr controlar la tiritona. Su uso de forma sistemática no se recomienda ya que se puede enmascarar la aparición de crisis convulsivas que se desarrollan en el 3-44% de los pacientes postparada (24). En el caso de ser necesario se recomienda el uso de EEG continuo para la monitorización de la aparición de crisis.

2.4.6. Monitorización y recalentamiento
El “Gold Standard” de la monitorización de la temperatura es la medición a través de una vena central. Si no se encuentra disponible la segunda mejor opción es la monitorización de la temperatura esofágica.

El recalentamiento se debe realizar de una forma lenta a una velocidad que no exceda 0,2 – 0,5 ºC por hora para evitar la aparición de hiperkalemia, edema cerebral y crisis convulsivas (25).

Retirar de forma progresiva las medidas físicas suele ser suficiente para lograr el recalentamiento, en caso de no conseguirse el uso de dispositivos externos como mantas de calor pueden ser necesarios.

2.4.7. Efectos adversos potenciales
El uso de la HT puede afectar varios procesos fisiológicos, siendo los más importantes:

  • Coagulopatía leve: con temperaturas inferiores a 35ºC se disminuye la actividad de las enzimas de la coagulación y la actividad de las plaquetas (26). Sin embargo la incidencia de sangrado en pacientes tratados con HT no es superior a los que se mantienen normotérmicos (27).
  • Disfunción de la función leucocitaria: la incidencia de infecciones tiende a incrementarse en los pacientes que se mantienen hipotérmicos por más de 24 horas. (28). Sin embargo estas infecciones no se acompañaron de mayor mortalidad.
  • Disminución de la conducción cardiaca: lo que puede provocar arritmias, incluyendo bradicardias y prolongación del QT (29). Sin embargo la presencia de bradicardia hasta 40 latidos por minuto suele ser bien tolerada y no requiere tratamiento si la tensión arterial media es mayor de 60 mmHg .
  • Aumento de la resistencia a la insulina: aumentando los requerimientos de insulina (30).
  • “Diuresis fría”: es el aumento de la diuresis por redistribución del volumen sanguíneo a órganos vitales (corazón, riñones, etc.) asociado a la hipotermia, puede causar hipovolemia, hipokalemia, hipomagnesemia e hipofosfatemia (31).

2.4.8. Beneficios de la HT
En una revisión sistemática realizada en 2012 (32) que incluía 481 pacientes, los datos acumulados demostraron que los pacientes tratados con HT presentaban un mejor rendimiento neurológico y una mayor posibilidad de sobrevivir al alta hospitalaria que los que no fueron tratados con HT.

En 2013 se realizó un estudio multinacional aleatorizado de 939 pacientes (19) que presentaron PCR extrahospitalaria y se recuperaron permaneciendo inconscientes. Los autores no encontraron diferencias en la mortalidad o en la función neurológica en el tratamiento con HT (33ºC) y el grupo de control de temperatura (36ºC).

Con respecto al ritmo cardiaco de presentación de la PCR:

    • En los pacientes que presentan TV sin pulso o FV de forma extrahospitalaria, existe controversia de la utilidad de la HT con estudios que están a favor (33,34) y autores que no encuentran diferencias entre HT y control de temperatura a 36ºC (19).
    • En los pacientes que se presentan sin ritmo desfibrilable: la HT ofrece un beneficio potencial en minimizar el daño neurológico independientemente de donde se ha producido la parada (intra o extrahospitalaria) (35).

3. Pronóstico de la RCP

Tras una RCP con recuperación de la circulación espontánea (RCE) es de vital importancia conocer el posible daño y probable pronóstico neurológico.

En general, en los estudios y publicaciones, se define “pobre resultado neurológico (PRN)” como valores en la escala CPC (“cerebral performance category” (36)) entre 3 y 5:

      • 3: discapacidad neurológica severa (dependiente para las actividades diarias)
      • 4: estado vegetativo persistente o coma
      • 5: muerte

Por el contrario, valores de CPC entre 1 y 2 se refieren a déficit neurológico ausente o leve-moderado, respectivamente.

No obstante, esto también varía en algunos estudios, donde consideran pobre resultado neurológico CPC de 4 y 5.

Se debe asignar al paciente el mejor valor de CPC obtenido durante su estancia hospitalaria.

Hechas estas consideraciones, podemos decir que actualmente existen 4 tipos de pruebas para predecir pobres resultados neurológicos:

      • Exploración clínica
      • Electrofisiología
      • Biomarcadores sanguíneos
      • Estudios de neuroimagen

3.1. Exploración clínica
Para que la exploración clínica sea válida para determinar un pronóstico, se debe asegurar que no hay interferencia de ninguna droga, teniendo en cuenta que el aclaramiento de fármacos es más lento con la hipotermia y que la propia hipotermia también disminuye la reactividad clínica.

Por tanto, durante los primeros días, los signos neurológicos de PRN tienen escaso valor pronóstico (la ausencia de reflejo pupilar en los primeros días se asoció con falso positivo en un tercio de los pacientes). En pacientes sin hipotermia, la fiabilidad de los signos clínicos es máxima a los 3 días de la RCE (37). Se sugiere que el momento en que es más fiable la exploración neurológica con hipotermia es 72 h tras recuperar la normotermia, es decir, 4-5 días tras la PCR (36), o incluso más. En hipotermia, sólo tiene valor pronóstico en la fase más temprana la ausencia de todos los reflejos de tronco, que ocurre en una minoría de pacientes.

En todo tipo de pacientes (con y sin hipotermia) el test más fiable a las 72 h o más de la PCR es la ausencia del reflejo pupilar a la luz (tasa de falsos positivos, FP 0%). La sensibilidad es de 29 y 18%, respectivamente. La fiabilidad de la observación cualitativa del reflejo es menor que el uso de detección cuantitativa, por ej. con pupilómetro.

La ausencia del reflejo corneal a las 72 h o más también detecta PRN, pero es un poco menos específico que el anterior (tasa FP 5% en un estudio sin hipotermia, y del 4% en 7 estudios con hipotermia) (38).

La sensibilidad de ambos reflejos es baja; sólo el 20-30% de los pacientes con pobres resultados tuvieron estos signos. El reflejo corneal se puede ver artefactado por efecto residual de relajantes neuromusculares y sedantes, no así el reflejo pupilar (mediado por la acción del parasimpático sobre el esfínter de la pupila).

La respuesta motora al dolor 48-72 h tras suspender la sedación, indica buen pronóstico cuando se obtiene respuesta localizadora (GCS-M ≥ 5). Si, por el contrario, no hay respuesta al dolor, o es extensora, (GCS-M ≤ 2), a las 72 h, predice mal pronóstico en el 80% de los casos (36), aunque la tasa de falsos positivos es alta (27%) porque se puede artefactar por efectos residuales de sedación y relajación neuromuscular.

Crisis y mioclonías: Las mioclonías son frecuentes tras PCR. Pueden estar asociadas o no a actividad epiléptica en el EEG. Las sacudidas ocasionales no tienen valor pronóstico: el 9% de los pacientes que las presentaron tuvo buenos resultados neurológicos.

El estatus mioclónico (mioclonías generalizadas en cara, tronco y extremidades que duran más de 30 min), sí tiene mal pronóstico en el paciente en coma tras PCR, y se asocia a PRN, sobre todo si ocurre el primer día tras la parada. Con la hipotermia terapéutica se observa menos frecuente en estadios tempranos, porque se controla fácilmente con sedación. De todas formas, se han descrito casos de buena recuperación neurológica tras estatus mioclónico, por lo que no se debe emplear para decidir limitación de esfuerzo terapéutico (36).

El estatus mioclónico se debe diferenciar del síndrome Lance-Adams (37), que consiste en la presencia, de forma crónica, de mioclonías en paciente consciente, que aparece generalmente más tarde tras la anoxia y con el movimiento voluntario del músculo.

Recomendaciones (38): Las evidencias actuales permiten enumerar una serie de recomendaciones para el uso de la exploración clínica como predictor pronóstico:

      • Usar la ausencia bilateral de reflejos pupilares y corneal a las 72 h o más de la RCE para predecir PRN, tanto en tratados como no tratados con hipotermia.
      • Si existen dudas de efectos residuales de sedación/bloqueantes neuromusculares, prolongar la observación de signos clínicos, más allá de las 72 h, para evitar falsos positivos.
      • No usar el componente motor de GCS ≤ 2 de forma aislada para predecir PRN por alta tasa de FP. Es muy sensible, por lo que es útil para detectar pacientes con más probabilidad de PRN, y se debe emplear en combinación con otros predictores.
      • Usar la presencia de estatus mioclónico en las primeras 48 h tras PCR como predictor de PRN junto con otros predictores.
      • Se debe evaluar al paciente sin sedación si es posible y realizar EEG para valorar otros signos de mal pronóstico o crisis epilépticas asociados al estatus epiléptico.

3.2. Estudios neurofisiológicos
3.2.1. Electroencefalografía (EEG):
Esta técnica consiste en el registro y análisis de la actividad bioeléctrica generada por la actividad sináptica en la corteza cerebral (39). En general, el registro en la Unidad de Reanimación (REA) se lleva a cabo mediante electrodos de aguja subcutáneos colocados en el cuero cabelludo (scalp). Sin embargo, cuando el nivel de conciencia del paciente es bueno, se utilizan electrodos de contacto. Un aspecto de gran importancia a la hora de valorar los registros de EEG en REA es la condición de sedación habitual en alguno de estos pacientes ya que la utilización de diferentes hipnóticos modifica las características del EEG. Otros fármacos, como los antiepilépticos, las benzodiacepinas o los neurolépticos también modifican el registro. Por tanto, es fundamental conocer los fármacos que se le están administrando al paciente.

figura1-resucitacion-cerebral

Figura 1. Electroencefalografía. A) Coma theta en paciente con encefalopatía post-anóxica. El paciente está en estado vegetativo persistente. B) Registro que muestra una crisis eléctrica generalizada en paciente en coma tras una encefalopatía post-anóxica.

 

Una de las principales ventajas del EEG es la posibilidad de la realización de estudios seriados o la monitorización de larga duración. En este caso, además de valorar la funcionalidad de la corteza cerebral, resulta muy importante para establecer el grado de afectación de las estructuras centrales, conocer la existencia de ritmo circadiano y de fases fisiológicas de sueño.

En los pacientes que han sufrido un cuadro de anoxia/isquemia cerebral, es importante tener en cuenta que la sensibilidad a la isquemia varía según la región cerebral afectada. Las áreas más sensibles a la hipoperfusión son la materia gris, las regiones más rostrales y aquellas zonas que limitan los territorios de las grandes arterias. Inicialmente se produce un déficit reversible en la conducción neural y en la neurotransmisión, que si se prolonga en el tiempo se puede asociar con destrucción y muerte neuronal, dependiendo de la severidad de la isquemia. Se asume de forma general, que la transmisión sináptica es el primer proceso en fallar durante una isquemia cerebral, por lo tanto la señal del EEG es muy sensible a los efectos de la isquemia (40). Además, la anoxia cerebral ocasiona una incidencia de crisis epilépticas no convulsivas de hasta el 40%, y de estatus no convulsivos de un 33% (41,42) (Figura 1).

Los cambios en el EEG observados tras una PCR abarcan desde un patrón de actividad lenta difusa no específica hasta la inactividad electrocerebral. Existen patrones y características del EEG que se observan en encefalopatías hipóxicas, y que si bien es cierto, no son específicos para ninguna etiología, reflejan diferentes grados de disfunción cerebral y la profundidad del coma.

Los llamados patrones “malignos” en el EEG comprenden el brote-supresión, coma alfa o theta y actividad delta de bajo voltaje. Además la presencia de descargas periódicas generalizadas (DPGs) sobre una actividad de fondo suprimida (en ausencia de sedación) se encuentran frecuentemente después de una parada cardíaca y son indicativos de mal pronóstico (40,43,44). Cuando estas descargas son bilaterales independientes (Bi-PLEDs) o ictales periódicas inducidas por estímulos (SIRPID) indican una condición más severa (44).

Los patrones benignos con reactividad de la actividad de fondo en el EEG son un factor pronóstico favorable en la encefalopatía hipóxica. Por el contrario, la ausencia de reactividad a estímulos externos se relaciona con un mal pronóstico (40,43,44).

La presencia de crisis epilépticas convulsivas o no convulsivas implica una severa pero incompleta, destrucción de estructuras corticales. Por lo que son un factor predictivo de mal pronóstico (42,44).

El EEG de bajo voltaje (< 20µV) en el contexto de un paciente con encefalopatía hipóxica, suele ser el patrón precursor de la inactividad bioeléctrica cerebral, que es el hallazgo electroencefalográfico que confirma la muerte cerebral (44,45).

3.2.2. Potenciales evocados somatosensoriales(PESS):
Consisten en el registro de la actividad cortical generada en la corteza somatosensorial primaria (áreas 3,1 y 2 de Brodmann) en respuesta a un estímulo sobre un nervio periférico contralateral (39). Los PESS de uso habitual valoran la conducción de cordones posteriores en la médula espinal, así como la del tronco del encéfalo, haz tálamo cortical y corteza somato-sensorial, que es la estructura valorada en casos de encefalopatía post-anóxica. El registro se realiza en C3’/C4’ (5 cm laterales al vértex y 2 cm posteriores)-Fpz para PESS de miembros superiores, y en Cz’-Fpz para miembros inferiores.

Numerosos estudios han demostrado que la ausencia bilateral de N20 en los PESS pasadas las 24 horas tras el inicio del coma anóxico, se asocian con muerte o estado vegetativo persistente (38,40,45), con una predicción del 100% según las guías de la Academia Americana de Neurología (AAN) del 2006 (43). Además se ha observado que la hipotermia terapéutica no altera los PESS, por lo que incluso bajo esta condición, su uso y valor pronóstico sigue siendo el mejor para la valoración de estos pacientes (41, 43, 46, 47).

Como conclusión, podemos decir que las pruebas neurofisiológicas son estudios complementarios insustituibles en pacientes con alteración del nivel de conciencia/sedados, especialmente en aquellos que han sufrido isquemia/hipoxia cerebral por cualquier causa. Está demostrado su valor diagnóstico (a pesar de su relativa inespecificidad) y pronóstico, por lo que permiten tomar decisiones precoces y acertadas al equipo médico. Se trata, además de estudios fácilmente repetibles, baratos en términos económicos y que pueden realizarse sin desplazar al paciente de REA, por lo que entendemos que su empleo debería ser más extendido, de acuerdo con la evidencia científica y su eficiencia.

3.3. Biomarcadores sanguíneos (37)
La enolasa neuronal específica (NSE) y la proteína S-100β se liberan tras daño neuronal y de las células gliales, respectivamente.

Los niveles en sangre tras una PCR se correlacionan con la extensión del daño y resultados neurológicos.

El principal problema de su uso es que no hay definido un valor umbral que permita predecir PRN sin falsos positivos. Además, la hipotermia modifica la liberación de NSE, elevando los valores sanguíneos que se consideran indicativos de mala evolución neurológica.

El valor recomendado por la American Heart Association de NSE >33 µg/l en los días 1-3 tras PCR tiene una tasa de FP de 29,3% en pacientes tratados con hipotermia (48).

Estos valores varían mucho de unos estudios a otros, por lo que no se puede establecer claramente una cifra que se asocie a PRN:

Para la NSE oscila entre 15-90 µg/l a las 72 h en no tratados con hipotermia, y de 57,2 a 78,9 µg/l a las 72 h en los tratados con hipotermia. De manera práctica, valores > 60 µg/l a las 48-72 h detectan PRN con excepcionales falsos positivos (38).

Valores de proteína S-100β de 0,12-0,8 µg/l a las 72 h predicen PRN.

Las razones de esta variabilidad en los niveles pueden ser la liberación aumentada de origen extracerebral de ambas proteínas (la NSE en determinados tumores, hemólisis, y la proteína S-100β se puede elevar con las compresiones del masaje cardiaco, por ejemplo (36)) y las diferentes técnicas de laboratorio empleadas. Además, se correlacionan con el daño celular, pero no con la capacidad funcional de esas células (y por tanto, tampoco con el resultado neurológico).

Por todo ello, la recomendación (38) es emplear los valores elevados de ambas proteínas a las 48-72 h de la PCR (y sobre todo la tendencia, más que los valores absolutos) en combinación con otros predictores, para pronosticar PRN, tanto en tratados como no tratados con hipotermia, aunque no hay un valor umbral que permita descartar por completo falsos positivos.

3.4. Estudios de neuroimagen
La mayoría de los estudios sobre la utilidad pronóstica de las pruebas de neuroimagen tienen tamaños muestrales pequeños y son retrospectivos, lo que conlleva una evidencia científica débil.

Sin embargo, existen una serie de signos o hallazgos de TAC o resonancia magnética nuclear (RMN) con cierta capacidad pronóstica.

La TAC cerebral en el paciente en coma tras PCR sirve para excluir otras causas de coma o patologías que hayan provocado la PCR. En el paciente en coma por encefalopatía postanóxica el principal hallazgo es edema cerebral, que provoca borrado de surcos y una disminución de la tasa “densidad sustancia gris/densidad sustancia blanca” (GWR), debido a la disminución de densidad en la sustancia gris.

Una GWR global menor de 1,14 o GWR menor de 1,22 a nivel de los ganglios basales en TAC realizado 1 h después de la PCR predice PRN con especificidad de 100% (37). La reducción de GWR o el borrado de surcos en la TAC en las primeras 24 h tras la PCR es útil para predecir PRN.

La RMN detecta adecuadamente edema neuronal citotóxico, sobre todo en ganglios basales y zonas corticales posteriores. El mejor momento para realizarla con fines pronósticos es entre los días 3 y 5 tras parada para las estructuras corticales y entre los días 6 y 8 para las subcorticales (38). Es más sensible que la TAC para detectar cambios isquémicos, aunque es más difícil de llevar a cabo en pacientes inestables.

Los hallazgos que se asocian a PRN son: Cambios extensos multilobares en la RMN por difusión (DWI, diffusion weighted imaging) o en secuencias FLAIR dentro de los 5 días tras parada. Ambos se asocian en algunos estudios con muerte o estado vegetativo persistente (38). La severidad del daño y edema en la DWI se puede cuantificar con el coeficiente de difusión aparente (ADC). Los valores de ADC que predicen PRN sin falsos positivos no están claros y varían según los estudios.

Los estudios de neuroimagen tienen la ventaja de que no se artefactan por la sedación, relajación neuromuscular o el uso de hipotermia. Sin embargo, la interpretación es más compleja que para otros predictores, sujeta a variabilidad interobservador, y no hay descritos unos valores que permitan pronosticar PRN sin falsos positivos.

Son útiles, por tanto, en el abordaje pronóstico multimodal, junto con otros predictores, no de forma aislada. Y sólo se deben emplear en centros con marcada experiencia en este tipo de pruebas (38).

4. Conceptos claves

De forma práctica, el establecimiento de un pronóstico neurológico tras PCR debe comenzar con la exploración clínica, una vez que se descarten los efectos residuales de sedación y relajación neuromuscular, en paciente normotérmico, generalmente tras 72 h de la parada. Se deben haber suspendido los fármacos sedantes un mínimo de 12 h antes de la exploración (o más si ha estado hipotérmico), para que sea valorable.

A las 72 h, si la respuesta al dolor es extensora o nula (GCS-M = 1-2), el pronóstico se debe basar en los predictores que han demostrado ser más fiables:

La ausencia bilateral de reflejos pupilares a la luz y/o de N20 en los PESS implica PRN con mucha probabilidad con una tasa de falsos positivos <5%. Incluso, en pacientes no tratados con hipotermia, la ausencia bilateral de N20 ya tiene valor pronóstico pasadas 24 h o más desde la PCR.

La ausencia bilateral de reflejos corneales, añade mayor fiabilidad pronóstica a las dos pruebas anteriores.

Si ninguno de los predictores anteriores está presente, además de volver a reevaluar pasadas al menos 24 horas, se debe basar el pronóstico en otros predictores menos consistentes. El pronóstico neurológico es malo probablemente si el paciente presenta dos o más de los siguientes:

  • Estatus mioclónico en las primeras 48 h
  • Niveles altos de enolasa neuronal específica a las 48-72 h de la PCR
  • Patrón de brote supresión o estatus epiléptico en EEG tras el recalentamiento
  • Daño anóxico difuso en TAC o RMN (marcada reducción de GWR o borrado de surcos en TAC en las primeras 24 h, o cambios isquémicos difusos en RMN entre 2 y 5 días tras PCR).

Como norma general, se debe realizar un abordaje pronóstico multimodal, teniendo en cuenta varios predictores, ya que en muchas ocasiones conllevan una limitación de esfuerzo terapéutico. El objetivo es llegar a un pronóstico certero evitando el fenómeno de la “profecía que se cumple a sí misma”. Siempre que existan dudas, o el pronóstico sea incierto, se deberán repetir las exploraciones pasado un tiempo de observación, teniendo en cuenta que la mayoría de los pacientes en coma recuperan la conciencia en la primera semana tras la PCR.

 

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Fernando Ramasco Rueda (1), Jesús M Nieves Alonso (1), Angela de Abreu (2), Eva de Dios Tomás (1), Lorena Carolina Vega Zelaya (3)
(1) FEA de Anestesia y Reanimación del H.U. de La Princesa. Madrid
(2) Médico Residente. Servicio de Neurofisiología del H.U. de La Princesa. Madrid
(3) FEA Neurofisiología Clínica del H. U. de La Princesa. Madrid

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