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Publicado el 17 de mayo de 2017 | http://doi.org/10.5867/medwave.2017.6952

¿Es efectiva la ketamina endovenosa para el manejo del dolor postoperatorio en adultos?

Is intravenous ketamine effective for postoperative pain management in adults?

Camila Stuardo , Diego Lobos-Urbina, Fernando Altermatt

Resumen

La ketamina es un antagonista de los receptores de N-metil-D-aspartato que ha sido utilizada como adyuvante en el manejo agudo del dolor postoperatorio debido a sus propiedades analgésicas. Sin embargo, su rol no está claramente determinado. Para aclarar esta interrogante utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en multiples fuentes de información. Identificamos 19 revisiones sistemáticas que en conjunto incluyen 226 ensayos aleatorizados. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de ketamina endovenosa probablemente no produce una disminución del dolor postoperatorio, o esta es clínicamente irrelevante.

Problema

El manejo del dolor postoperatorio es un aspecto importante dentro de la práctica de la anestesiología. Entre las drogas más utilizadas para manejar el dolor agudo se encuentran los opioides, los cuales pese a ser muy efectivos, poseen efectos adversos como náuseas, vómitos, sedación y depresión respiratoria. Una de las estrategias para reducir estos efectos no deseados es utilizar analgésicos adyudantes que actúen a través de distintas vías involucradas en la respuesta al dolor.

El receptor de N-metil-D-aspartato (NMDA) es un receptor ionotrópico de glutamato que ha sido implicado en la modulación de mecanismos de dolor. La ketamina es un antagonista no competitivo de los receptores NMDA y se ha utilizado en dosis bajas como adyuvante en el manejo del dolor postoperatorio. Sin embargo, su uso clínico aún es controvertido debido a sus potenciales efectos adversos psicomiméticos como náuseas, mareos y alucinaciones.

Métodos

Utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples fuentes de información, para identificar revisiones sistemáticas y sus estudios primarios incluidos. Con esta información generamos un resumen estructurado, siguiendo un formato preestablecido, que incluye mensajes clave, un resumen del conjunto de evidencia (presentado como matriz de evidencia en Epistemonikos), metanálisis del total de los estudios, tablas de resumen de resultados con el método GRADE, y tabla de otras consideraciones para la toma de decisión.

Mensajes clave

  • El uso de ketamina endovenosa probablemente no produce una disminución del dolor postoperatorio, o esta es clínicamente irrelevante.
  • El uso de ketamina endovenosa probablemente no aumenta la sedación en el periodo postoperatorio, pero no está claro cuál es el efecto en la aparición de náuseas y vómitos porque la certeza de la evidencia es muy baja.

Acerca del conjunto de evidencia para esta pregunta

Cuál es la evidencia. 
Véase matriz de evidencia en Epistemonikos más abajo.

Encontramos 19 revisiones sistemáticas [1-19] que incluyen 226 [20-245] ensayos aleatorizados. De estos, hay 111 que incluyen el uso de ketamina endovenosa en pacientes adultos, que corresponde a la pregunta abordada por este resumen [20-130]

Qué tipo de pacientes incluyeron los estudios*

En 30 estudios se consideraron pacientes sometidos a cirugía abdominal [20],[21],[22],[23],[24],[25],[26],[27],
[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],
[40],[41],[42],[43],[44],[45],[46],[47],[48],[49] en 16 estudios pacientes sometidos a cirugía pélvica o ginecológica [50],[51],[52],[53],[54],[55],[56],[57],[58],
[59],[60],[61],[62],[63],[64],[65], en ocho estudios pacientes sometidos a cirugía traumatológica [20],[66],[67],[68],[69],[70],[71],[72], en siete estudios pacientes sometidos a cirugía de tórax [20],[21],[73],[74],[75],[76],[77] y en cinco estudios pacientes sometidos a otro tipo de cirugías [78],[79],[80],[81],[82]. El resto no reportó el tipo de cirugía al que eran sometidos los pacientes.

Qué tipo de intervenciones incluyeron los estudios*

Todos los estudios utilizaron ketamina de administración endovenosa.

En 33 estudios se utilizó ketamina en bolo [21],[22],[25],
[26],[27],[32],[33],[35],[38],[39],[41],[44],[50],[51],[52],
[53],[54],[55],[57],[59],[60],[61],[62],[66],[67],[68],[87],
[88],[90],[94],[96],[102],[124], en nueve estudios ketamina en infusión continua [49],[58],[74],[76],[81],
[85],[93],[100],[119], mientras que en 35 estudios se utilizaron ambos tipos de administración [20],[23],[29],
[30],[31],[34],[36],[37],[40],[43],[45],[46],[48],[56],
[63],[69],[70],[71],[72],[73],[75],[78],[79],[80],[82],
[84],[86],[89],[91],[107],[112],[116],[121],[122],[125]. El resto no fue reportado.

En 16 estudios se administró ketamina durante el preoperatorio [21],[22],[25],[33],[40],[50],[54],[55],[59],
[61],[66],[68],[102],[115],[119],[124], en 21 estudios se administró ketamina intraoperatoria [23],[29],[36],[41],
[43],[44],[48],[49],[56],[64],[74],[79],[80],[86],[87],
[90],[94],[97],[98],[107],[121], en 14 estudios se administró ketamina postoperatoria [24],[32],[35],[45],[52],[58],[78],[85],[91],[93] [110],[112],[114],[126], en dos estudios se administró pre e intraoperatoria [77],[116], en tres estudios se administró preoperatorio y luego en el postoperatorio [38],[67],[89], en 16 estudios se administró en el intraoperatorio y luego postoperatorio [20],[30],[31],[34],[37],[46],[63],[69],[70] [71],[72],[75],[81],[84],[122],[125], en 2 estudios se administró en el preoperatorio y luego en el intra y postoperatorio [63],[117], y en el resto de los estudios no fue reportado.

Las dosis utilizadas cuando se administró ketamina en bolo variaron entre 0,05 mg/kg y 2 mg/kg.

Las dosis utilizadas en infusión continua variaron entre: 0,002 mg/kg/hora y 1 mg/kg/hora.

Treinta y tres estudios reportaron coadministración de opioides [22],[25],[27],[31],[32],[33],[35],[36],[38],[40],
[44],[45],[46],[50],[54],[56],[58],[59],[63],[66],[67],[68],
[71],[78],[79],[80],[82],[88],[89],[94],[98],[119],[124].

Sesenta y dos estudios compararon contra placebo [20],[21] [23],[25],[26][29],[31],[32],[34],[35],[37],[38],[39],[41] [43],[44],[45],[46],[48],[49],[50][51],[53],[55],[56],
[58],[60],[61],[64],[66],[67],[68],[69],[70],[71],[72],[73],
[74],[75],[76],[78],[79],[80],[81],[82],[84],[85],[89],[93],
[94],[96],[98],[100],[102],[107],[112],[116],[119],[121],
[122],[124],[125], 13 estudios compararon contra otras drogas, especialmente opioides [22],[33],[36],[40],[52],
[54],[57],[59],[62],[63],[88],[91],[96] y en el resto de los estudios no fue reportado.

Qué tipo de desenlaces midieron

Los principales desenlaces analizados por las revisiones sistemáticas fueron: dolor postoperatorio, consumo perioperatorio de analgesia (opioides y otros), tiempo de solicitud de primera analgesia, tiempo de cirugía, tiempo de anestesia, náuseas y vómitos postoperatorios y otros efectos adversos (como sueños desagradables, efectos cognitivos y psicológicos, hipotensión y calofríos). 

* La información sobre los estudios primarios es extraída desde las revisiones sistemáticas identificadas, no directamente desde los estudios, a menos que se especifique lo contrario.

Resumen de los resultados

No fue posible extraer suficiente cantidad de información desde las revisiones identificadas como para reconstruir el metanálisis y la tabla de resumen de resultados. Por lo tanto, la información presentada se basa en las conclusiones por separado de las nueve revisiones sistemáticas que realizaron metanálisis para alguno de los desenlaces de interés [5],[6],[7],[10],[11],[14],[16],[19], es decir, dolor a las 24 horas del postoperatorio [5],[6],[7],[10],[11],[16], presencia de náuseas y vómitos postoperatorios [5],[6],[7],[10],[11],[16],[19] y sedación [9],[10],[14].

El resumen de los resultados es el siguiente:

  • El uso de ketamina endovenosa probablemente no produce una disminución del dolor postoperatorio, o esta es clínicamente irrelevante. La certeza de la evidencia es moderada.
  • No está claro cuál es el efecto de la ketamina endovenosa en la aparición de náuseas y vómitos postoperatorios porque la certeza de la evidencia es muy baja.
  • El uso de ketamina endovenosa probablemente no aumenta la sedación en el periodo postoperatorio. La certeza de la evidencia es moderada.



Otras consideraciones para la toma de decisión

A quién se aplica y a quién no se aplica esta evidencia
  • Los resultados de este resumen son aplicables a los pacientes adultos a los que se realizan cirugías tanto abdominales, traumatológicas, torácicas, pélvicas o ginecológicas y que son sometidos a anestesia general o neuroaxial.
Sobre los desenlaces incluidos en este resumen
  • Entre los desenlaces evaluados se encuentran aquellos considerados críticos para la toma de decisión por los autores de este resumen. En general coinciden con los utilizados por las revisiones identificadas.
Balance riesgo/beneficio y certeza de la evidencia
  • Se trata de una intervención que muy probablemente no tiene beneficios, por lo que no corresponde estimar un balance entre beneficios y riesgos. 
Qué piensan los pacientes y sus tratantes
  • Frente a la evidencia presentada en este resumen la mayoría de los clínicos debieran inclinarse en contra de su utilización.
Consideraciones de recursos
  • Se trata de una intervención que muy probablemente no tiene beneficios, por lo que no corresponden estimar un balance entre beneficios y costos. 
Diferencias entre este resumen y otras fuentes
  • Las revisiones identificadas discrepan entre sí. Una de las principales razones es que analizan una proporción baja de los estudios identificados en este resumen.
  • Las principales guías clínicas también entregan recomendaciones discordantes. Por ejemplo las Practice Guidelines for Acute Pain Management in the Perioperative Setting [246] de la American Society of Anesthesiologists no realizan un comentario claro sobre el uso de ketamina como coadyuvante en analgesia perioperatoria; la guía Acute pain management: scientific evidence [247] del Australian and New Zealand College of Anaesthetists (ANZCA) recomienda el uso de la ketamina endovenosa para la reducción del dolor, la reducción de las náuseas y vómitos postoperatorias y la disminución del tiempo hasta la solicitud de primera analgesia, sobre todo en pacientes sometidos a cirugía torácica, abdominal alta y cirugía traumatológica. Cabe destacar que las conclusiones emitidas por la ANZCA se basan principalmente en la revisión sistemática hecha por Laskowski [10] y por tanto incorporan solo algunos de los estudios analizados por este resumen.
¿Puede que cambie esta información en el futuro?
  • La probabilidad que futuros estudios cambien las conclusiones de este resumen es baja, debido al nivel de certeza existente.
  • Se realizó una busqueda en la International Clinical Trial Registry Platform de la Organización Mundial de la Salud, sin encontrarse nuevos estudios primarios en curso que traten sobre esta temática. En una búsqueda en PubMed identificamos al menos tres [248],[249],[250] ensayos aleatorizados que abordan el problema y que no están incluidos en las revisiones sistemáticas identificadas.
  • Considerando la abundancia de estudios encontrados, la escasa cobertura de las revisiones sistemáticas existentes y las limitaciones metodológicas de estas, es muy probable que una nueva revisión sistemática, con métodos rigurosos de identificación y análisis podría aportar nuevas luces sobre este tópico.
  • En una búsqueda en el International prospective register of systematic reviews (PROSPERO), no identificamos ninguna revisión en curso que esté abordando esta pregunta.

Cómo realizamos este resumen

Mediante métodos automatizados y colaborativos recopilamos toda la evidencia relevante para la pregunta de interés y la presentamos en una matriz de evidencia.

Siga el enlace para acceder a la versión interactiva: Ketamina para el dolor postoperatorio

Notas

Si con posterioridad a la publicación de este resumen se publican nuevas revisiones sistemáticas sobre este tema, en la parte superior de la matriz se mostrará un aviso de “nueva evidencia”.  Si bien el proyecto contempla la actualización periódica de estos resúmenes, los usuarios están invitados a comentar en Medwave o contactar a los autores mediante correo electrónico si creen que hay evidencia que motive una actualización más rápida.

Luego de crear una cuenta en Epistemonikos, al guardar las matrices recibirá notificaciones automáticas cada vez que exista nueva evidencia que potencialmente responda a esta pregunta. El detalle de los métodos para elaborar este resumen están descritos aquí: http://dx.doi.org/10.5867/medwave.2014.06.5997.

La Fundación Epistemonikos es una organización que busca acercar la información a quienes toman decisiones en salud, mediante el uso de tecnologías. Su principal desarrollo es la base de datos Epistemonikos (www.epistemonikos.org).

Los resúmenes de evidencia siguen un riguroso proceso de revisión por pares interno.

Declaración de conflictos de intereses
Los autores declaran no tener conflictos de intereses con la materia de este artículo.

Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

Autores

Camila Stuardo

fernando.altermatt@gmail.com.

Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 476, Santiago Centro, Chile

Diego Lobos-Urbina

Fernando Altermatt

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Historial

Citación Stuardo C, Lobos-Urbina D, Altermatt F. Is intravenous ketamine effective for postoperative pain management in adults? . Medwave 2017;17(Suppl2):e6952 doi: 10.5867/medwave.2017.6952

Envío 27/03/2015

Aceptación 28/04/2016

Publicación 17/05/2017

Métricas del artículo

Artículo no tiene métricas.

Notas

Referencias

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