SISTEMA DE ELIMINACIÓN EXTRACORPÓREA DE CO2 MINIMAMENTE INVASIVA
WWW.CARDIOLINKGROUP.COM SISTEMA DE ELIMINACIÓN EXTRACORPÓREA DE CO 2 MINIMAMENTE INVASIVA
INDICACIONES:
La respiración celular produce CO 2 continuamente. En casos de insuficiencia respiratoria alveolar, se puede desencadenar un aumento de dióxido de carbono (hipercapnia) y como consecuencia, una disminución significante en el pH (acidosis respiratoria). La corrección de ambas podría conseguirse mediante técnicas convencionales, pero no siempre es suficiente:
En pacientes con acidosis respiratoria refractaria al soporte de VNI, la eliminación extracorpórea de CO 2 permite la extensión con dicho EXACERBACIÓN EPOC soporte, evitando la intubación, sedación y ventilación mecánica, con un menor riesgo de infecciones nosocomiales.5
En paciente con SDRA e hipercapnia severa refractaria con ventilación 1,2 mecánica protectora, la eliminación extracorpórea de CO2 permite SDRA limitar el volumen y la presión de la ventilación mecánica, evitando daños pulmonares como barotrauma y volutrauma 3
En pacientes que desarrollan disfunción primaria de injerto 6 postquirúrgico, asociado con hipercapnia severa, la eliminación TRASPLANTE PULMONAR extracorpórea de CO2 permite limitar la alta presión y volumen de la ventilación, y por tanto, evitar daños al órgano trasplantado.
En presencia de lesiones tisulares del sistema respiratorio (fístula LESIÓN TISULAR broncopleural, ruptura de tráquea o daño diafragmático), la posibilidad de reducir el volumen y la presión en la ventilación, acelera la cicatrización 8,9
En pacientes con daño cerebral y fallo respiratorio, la eliminación de 7 CO 2 extracorpórea ayuda a controlar la presión intracraneal, además DAÑO CEREBRAL de los límites de presión y volúmenes de ventilación y el daño TRAUMÁTICO potencial inducido por la ventilación mecánica en el pulmón. SISTEMA DE ELIMINACIÓN EXTRACORPÓREA DE CO 2 MINIMAMENTE INVASIVA
MÉTODO:
El CO2 producido constantemente por la respiración celular (250 ml/min) se equilibra a través de la ventilación alveolar, gracias a un flujo de 4 L/min de aire aproximado.
INSUFICIENCIA RESPIRATORIA
O2 HIPOXEMIA - FALLO RESPIRATORIO POR OXIGENACIÓN INSUFICIENTE
CO2 HIPERCAPNIA - FALLO EN VENTILACIÓN
EXACERBACIÓN EPOC
VNI SISTEMA DE ELIMINACIÓN EXTRACORPÓREA DE CO2 MINIMAMENTE INVASIVA
SÍNDROME DISTRÉS RESPIRATORIO AGUDO
ECCO2 -R D A D I S N E T N I
300 200 100
0 400 2000 4000 Flujo sanguíneo ml/min SISTEMA DE ELIMINACIÓN EXTRACORPÓREA DE CO MINIMAMENTE INVASIVA 2
COMPOSICIÓN Y CARACTERÍSTICAS
BOMBA PERISTÁLTICA BAJO FLUJO : 450 ml/min
FLUJO DE AIRE
FLUJO DE EXTRACCIÓN CO2
GRÁFICO EVOLUCIÓN DE FLUJO EXTRACCIÓN CO2
SUMINISTRO AIRE MEDICINAL
MEDICIÓN EXACTA DE CO 2 EXTRAÍDO
Membrana semipermeable de Polimetilpenteno Recubrimiento de Fosforilcolina SUPERFICIE 1,8 m2 Volumen de cebado: 125 ml
CAPACIDAD DE EXTRACCIÓN CO2 >100 ml/min CE para LF-ECCO -R durante 5 días 2
ELEVADA capacidad de extracción extracorpórea de CO (>100 ml/min) 2 MÍNIMA invasividad (flujo < 500ml/min) FÁCIL manejo Volumen de cebado REDUCIDO AUSENCIA de pérdida de calor BARRIDO automático de gas SISTEMA DE ELIMINACIÓN EXTRACORPÓREA DE CO MINIMAMENTE INVASIVA 2
LF-ECCO 2 -R V S . ECMO
NO INVASIVO INVASIVO BOMBA PERISTÁLTICA BOMBA CENTRÍFUGA CATÉTER DOBLE LUZ < 14 Fr CATÉTER DOBLE LUZ > 15 Fr UN SOLO CATÉTER DOBLE CATÉTER CONEXIONES LUER-LOCK CONEXIONES ECMO < 450 ml/min > 2L/min SISTEMA DE ELIMINACIÓN EXTRACORPÓREA DE CO2 MINIMAMENTE INVASIVA
PRODUCTOS Y REFERENCIAS
BIBLIOGRAFÍA
1. The acute respiratory distress syndrome network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Eng J Med 2000; 342 (18): 103-1308. 2. Hager DN, Krishnan JA, Hayden DL et al. Tidal Volume Reduction in Patients with Acute Lung Injury When Plateau Pressures Are Not High. Am J Respir Crit Care Med 2005; 172: 1241-1245. 3. Determann RM, Royakkers A, Wolthuis EK et al. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Crit Care 2010; 14: R1-R14. 4. Confalonieri M, Garuti G, Cattaruzza MS et al. A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation. Eur Respir J 2005; 25: 348-355. 5. Conti G, Antonelli M, Navalesi P et al. Noninvasive vs. conventional mechanical ventilation in patients with chronic obstructive pulmonary disease after failure of medical treatment in the ward: a randomized trial. Int Care Med 2002; 28(12): 1701-7. 6. Prekker ME, Nath DS, Walker AR. Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation. J Heart Lung Transplant 2006; 25(4): 371-8. 7. Brian JE. Carbon Dioxide and the Cerebral Circulation. Anesthesiology 1998; 88(5): 1365-86. 8. Kolobov T, Gattinoni L, Tomlinson TA et al. Control of breathing using an extracorporeal membrane lung. Anesthesiology 1977; 46: 138-141. 9. Baumann MH, Sahn SA. Medical management and therapy of bronchopleural fistulas in the mechanically ventilated patient. Chest 1990; 97: 721-8. 10. Schinco MA, Formosa VA, Santora TA. Ventilatory management of a bronchopleural fistula following thoracic surgery. Respir Care 1998; 43: 1064-9. 11. Gattinoni L, Carlesso E, Langer T. Towards ultraprotective mechanical ventilation. Curr Opin Anaesthesiol 2012; 25(2): 141-7. BIBLIOGRAFÍA PROLUNG®
“SISTEMA DE EXTRACCIÓN DE CO2 EXTRACORPÓREO MÍNIMAMENTE INVASIVO PARA SOPORTE VENTILATORIO” [1-17]
1. Romay, E. and R. Ferrer, Extracorporeal CO2 removal: Technical and physiological fundaments and principal indications. Med Intensiva, 2015.
EXACERBACIÓN EPOC
2. Duscio, E., et al., Extracorporeal CO2 Removal: The Minimally Invasive Approach, Theory, and Practice. Crit Care Med, 2018.
3. Arcaro, G. and A. Vianello, The Successful Management of a Patient With Exacerbation of Non-Cystic Fibrosis Bronchiectasis and Bilateral Fibrothorax Using a Venovenous Extracorporeal Carbon Dioxide Removal System. Respir Care, 2014.
4. Morelli, A., et al., Extracorporeal CO2 removal in hypercapnic patients who fail noninvasive ventilation and refuse endotracheal intubation: a case series, in ESICM LIVES 2015. 2015, Intensive Care Medicine Experimental: Berlin. p. A824.
5. Pastore, A., et al., LFVVECCO2-R in COPD exacerbations: experience in two patients, in SIAARTI. 2013a: Rome.
6. Pisani, L., N. Corcione, and S. Nava, Management of acute hypercapnic respiratory failure. Curr Opin Crit Care, 2016.
7. Sucre, M.J., et al., Perché trattare il paziente BPCO in rianimazione con la decapneizzazione extracorporea, in SIAARTI. 2013a: Rome.
BIBLIOGRAFÍA PROLUNG®
“SISTEMA DE EXTRACCIÓN DE CO2 EXTRACORPÓREO MÍNIMAMENTE INVASIVO PARA SOPORTE VENTILATORIO” [1-17]
SDRA Y LESIONES PULMONARES ASOCIADAS A VENTILACIÓN MECÁNICA
8. Hilty, M.P., et al., Low flow veno-venous extracorporeal CO2 removal for acute hypercapnic respiratory failure. Minerva Anestesiol, 2017.
9. Pastore, A., et al., LFVVECCO2-R to provide "lung rest" in lesions of respiratory system: experience in one patient, in SIAARTI. 2013b: Rome.
10. Pisani, L., et al., Effects of Extracorporeal CO2 Removal on Inspiratory Effort and Respiratory Pattern in Patients Who Fail Weaning from Mechanical Ventilation. Am J Respir Crit Care Med, 2015. 192(11): p. 1392-4.
11. Sucre, M.J., et al., A type A (H1N1) influenza with ARDS treated with low-flow venovenous extracorporeal CO2 removal system, in SIAART. 2013b: Roma.
12. Visconti, F., et al., Usefulness of a VV extracorporeal CO2 removal device (ProLung) in severe pneumonia complicated by refractory bronchospasm, in 31th International Vicenza Course on Critical Care Nephrology. 2013: Vicenza.
TRASPLANTE PULMONAR
13. Ruberto, F., et al., Low-flow veno-venous extracorporeal CO2 removal: first clinical experience in lung transplant recipients. Int J Artif Organs, 2014. 37(12): p. 911-7.
14. Soluri-Martins, A., et al., How to minimise ventilator-induced lung injury in transplanted lungs: The role of protective ventilation and other strategies. Eur J AnAase spthreessioel,n 2t0e15d. by Stephen Chan 15. Vianello, A., et al., Extracorporeal CO2 removal for refractory hypercapnia in the event of acute respiratory failure. Minerva Pneumol., 2015. 54: p. 103-110.
16.F oVriaenwelolor, dA .,b eyt al., Successful management of acute respiratory failure in an idiopathic pulmonary fibrosis patient using an extracorporeal carbon dioxide removal sysAtenmd. rSearwco iPdohsais,n vasculitis and diffuse lung diseases, 2016. 33: p. 186-190.
17. Bergantino, B., et al., Extracorporeal carbon dioxide removal: a new low flow veno- veRnoeusse daervciche ibny lung transplantation, in ESICM. 2012: Lisbon. Andrea Chang
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REVISIÓN
Eliminación extracorpórea de CO2: fundamentos
fisiológicos y técnicos y principales indicaciones
a a,b,∗
E. Romay y R. Ferrer
a
Servicio de Medicina Intensiva, Hospital Universitario Mútua de Terrassa, Universidad de Barcelona, Terrassa, Barcelona, Espana˜
b
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Espana˜
Recibido el 29 de mayo de 2015; aceptado el 2 de junio de 2015
PALABRAS CLAVE Resumen Recientemente las mejoras tecnológicas han permitido reducir la complejidad de
Respiración artificial; los dispositivos de oxigenación por membrana extracorpórea, dando paso al desarrollo de dis-
Dióxido de carbono; positivos específicos para la eliminación extracorpórea de CO2. Estos dispositivos tienen un
Circulación montaje más simple y utilizan flujos sanguíneos más bajos, lo que potencialmente disminuye las
extracorpórea; complicaciones vasculares y hemodinámicas. Estudios experimentales han demostrado la fac-
Síndrome de distrés tibilidad, eficacia y seguridad de la eliminación extracorpórea de CO2 y algunos de sus efectos
respiratorio; en humanos.
Enfermedad Esta técnica, que fue concebida como un tratamiento complementario en los pacientes
pulmonar obstructiva con SDRA grave, permite la optimización de la ventilación protectora e incluso ha abierto el
crónica camino a nuevos conceptos, como lo que se ha denominado ventilación «ultraprotectora»’’,
cuyos beneficios aún están por determinarse. Además, la eliminación extracorpórea de CO2
se está implementando en pacientes con insuficiencia respiratoria hipercápnica agudizada con
resultados prometedores.
En esta revisión describiremos los fundamentos fisiológicos y técnicos de esta terapia y sus
distintas variantes, así como la evidencia clínica disponible hasta la fecha, enfocados en su
potencial en el paciente con insuficiencia respiratoria.
© 2015 Elsevier España, S.L.U. y SEMICYUC. Todos los derechos reservados.
KEYWORDS Extracorporeal CO2 removal: Technical and physiological fundaments and principal
Respiration, artificial; indications
Carbon dioxide;
Extracorporeal Abstract In recent years, technological improvements have reduced the complexity of extra-
circulation; corporeal membrane oxygenation devices. This have enabled the development of specific
devices for the extracorporeal removal of CO2. These devices have a simpler configuration
Respiratory distress
than extracorporeal membrane oxygenation devices and uses lower blood flows which could
syndrome, adult;
reduce the potential complications. Experimental studies have demonstrated the feasibility,
Pulmonary disease,
efficacy and safety of extracorporeal removal of CO2 and some of its effects in humans. chronic obstructive
∗
Autor para correspondencia.
Correo electrónico: [email protected] (R. Ferrer).
http://dx.doi.org/10.1016/j.medin.2015.06.001
0210-5691/© 2015 Elsevier España, S.L.U. y SEMICYUC. Todos los derechos reservados.
Cómo citar este artículo: Romay E, Ferrer R. Eliminación extracorpórea de CO2: fundamentos fisiológicos y técnicos y
principales indicaciones. Med Intensiva. 2015. http://dx.doi.org/10.1016/j.medin.2015.06.001
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MEDIN-810; No. of Pages 6 ARTICLE IN PRESS
2 E. Romay, R. Ferrer
This technique was initially conceived as an adjunct therapy in patients with severe acute
respiratory distress syndrome, as a tool to optimize protective ventilation. More recently, the
use of this technique has allowed the emergence of a relatively new concept called ‘‘tra-
protective ventilation’’whose effects are still to be determined. In addition, the extracorporeal
removal of CO2 has been used in patients with exacerbated hypercapnic respiratory failure with
promising results.
In this review we will describe the physiological and technical fundamentals of this therapy
and its variants as well as an overview of the available clinical evidence, focused on its current
potential.
© 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.
Introducción Efectos de la hipercapnia
Durante los últimos anos˜ diversas estrategias y mejoras tec- Los efectos de la hipercapnia han sido ampliamente anali-
nológicas han permitido reducir el tamano˜ y la complejidad zados en estudios con animales y corroborados en algunos
12,13
de los dispositivos de oxigenación por membrana y soporte estudios clínicos observacionales . La acidosis hipercáp-
extracorpóreo (ECMO), lo que ha permitido que su uso y nica, mientras a nivel de otros tejidos como el cerebro puede
1,2
seguridad hayan aumentado progresivamente . causar vasodilatación, a nivel pulmonar produce vasocons-
En consonancia con estos avances, y en aras de progre- tricción, aumentando la presión arterial pulmonar media, lo
sar en esa simplificación, Gattinoni y Kolobow fueron los cual, anadido˜ a los efectos de la ventilación de presión posi-
pioneros en describir la necesidad de disociar el soporte de tiva, conduce a un importante aumento de la poscarga del
14
oxigenación de un soporte extracorpóreo exclusivamente de ventrículo derecho . La hipertensión pulmonar inducida por
ventilación con el objetivo de optimizar la protección pul- la hipercapnia puede contribuir a la aparición de cor pulmo-
15
monar durante la ventilación mecánica. Así es como nace la nale en el paciente con SDRA y aumentar la mortalidad .
3
eliminación extracorpórea de CO2 (ECCO2R) . Estos dispo- Asimismo, la hipercapnia y la acidosis constituyen un factor
sitivos extraen CO2 de la sangre venosa mediante su paso de riesgo probado para la aparición de arritmias que incre-
a través de una membrana similar a la de las ECMO. La menta la complejidad del manejo de estos pacientes. A nivel
diferencia fundamental radica en que se utilizan flujos san- de otros tejidos, la acidosis hipercápnica puede aumentar la
guíneos mucho menores y, por tanto, cánulas arteriales o secreción gástrica y producir cierto grado de vasodilatación
4
venosas de menor tamano˜ . Su utilidad principal fue conce- sistémica.
bida inicialmente para los pacientes con síndrome de distrés Contrariamente, algunos estudios evidencian que la con-
respiratorio agudo (SDRA) grave, en los que la estrategia centración elevada de CO2 disminuye el dano˜ pulmonar
5
de ventilación protectora produce hipercapnia importante ; mediante la atenuación de los efectos de los radicales libres
16
sin embargo, más recientemente se está implementando y la disminución de la actividad de los neutrófilos y otros
también en pacientes con enfermedad pulmonar obstructiva factores inmunológicos, e incluso ejerce efectos protecto-
6 17
crónica (EPOC) agudizada . res ante el dano˜ pulmonar inducido por endotoxina . Sin
En el SDRA, la estrategia de la ARDSNet de utilizar un embargo, muchos de estos cambios pueden no ser explica-
bajo volumen corriente (Vc) (6-8 ml/Kg de peso ideal) para dos solo por la hipercapnia, sino por la acidosis, e incluso
disminuir la distensión pulmonar y una PEEP alta para mejo- ser independientes, tal y como ocurre en las monocapas
rar la oxigenación demostró un descenso importantísimo de epiteliales alveolares en las que la hipercapnia con pH com-
7 18
la mortalidad . Además, el fenómeno de hiperinsuflación pensado no produce beneficio e incluso puede causar dano˜ .
y de apertura y cierre alveolar conducen, per se, a una Diversos autores han propuesto utilizar ventilación mecá-
entidad denominada dano˜ inducido por el ventilador, que nica ultraprotectora (3-4 ml/Kg de peso ideal) combinada
8
se minimiza usando esta estrategia . En un análisis post con ECCO2R con la intención última de prevenir la lesión
hoc del estudio de la ARDSNet se observó que tanto los pulmonar aguda inducida por el ventilador. Esta estrate-
pacientes que recibían Vc bajo como alto se beneficiaban gia potencialmente evitaría los riesgos de la hipercapnia y
19,20
de una presión de meseta (Pplat) < 30 cmH2O, evidenciando reduciría las necesidades de sedación .
que pueden ser necesarias reducciones adicionales del Vc
9
para mantener la Pplat < 30 cmH2O . En esta misma línea,
Tecnología y fundamentos técnicos
se ha comprobado que el uso de Vc bajos puede preve-
10
nir el desarrollo de SDRA en pacientes en riesgo . Sin de la extracción extracorpórea de CO2
embargo, a pesar de los beneficios descritos, la adheren-
cia a la estrategia de ventilación protectiva aún dista de ser La simplificación técnica ha permitido que el desarrollo y
adecuada u homogénea, y en algunos casos puede llegar a potenciales aplicaciones de la extracción extracorpórea de
11
ser insuficiente . CO2 (ECCO2R) avancen de forma rápida, evitando algunos
Cómo citar este artículo: Romay E, Ferrer R. Eliminación extracorpórea de CO2: fundamentos fisiológicos y técnicos y
principales indicaciones. Med Intensiva. 2015. http://dx.doi.org/10.1016/j.medin.2015.06.001
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Eliminación extracorpórea de CO2: fisiología, técnicas e indicaciones 3
Tabla 1 Características técnicas de los diferentes dispositivos de eliminación extracorpórea de CO2
Dispositivo Tipo de terapia Bomba Membrana (material); Flujo de Volumen de
2
superficie en m sangre purgado (ml) (L/min)
®
Maquet PALP V-V/V-A/A-V Rotor magnético PMP (opción de 0,2-2,8 247 ®
CardioHelp cobertura con ®
Bioline ); 0,98
®
Alung Hemolung V-V bajo flujo Centrífugo con PLP poroso con 0,35-0,55 259
membrana siloxano y heparina; integrada 0,59
®
Estor ProLUNG V-V bajo flujo Rodillo peristáltico PMP con cobertura de < 0,45 220
fosforilcolina; 1,8
Hemodec V-V bajo flujo Rodillo peristáltico PLP poroso; 1,35 < 0,4 140-160 DecapSmart®
®
Novalung iLA V-V bajo, Rotor diagonal PMP; 0,32 (MiniLung 0,5-4,5 240
®
Activve medio y alto petite) PMP; 1,3 flujo (iLA®)
®
Novalung iLA A-V - PMP; 1,3 (iLA ) < 1,5 240
Novalung®
A-V: arteriovenoso; PMP: poli-4-metil-1-penteno; PLP: polipropileno; V-A: venoarterial (oxigenación por membrana extracorpórea); V-V:
venovenoso.
de los problemas iniciales asociados a la ECMO. En este sen- mencionar la disponibilidad de dispositivos «sin bomba», que
tido, la ECCO2R es teóricamente más simple y requiere de utilizan el gradiente arteriovenoso de los pacientes para
menos logística y personal para su uso. De hecho, en el caso hacer fluir la sangre por la membrana extractora de CO2.
de los dispositivos de bajo flujo, la complejidad es similar a A continuación describimos brevemente los dispositivos
la presentada por las técnicas de reemplazo renal continuo, disponibles actualmente (tabla 1 y figura 1):
21
que son ahora prácticamente ubicuas .
La eliminación de CO2 es actualmente un paso interme-
Dispositivos arteriovenosos
dio entre el soporte ventilatorio convencional y el soporte
total con ECMO. Esto se justifica en el hecho de que es ® ®
Novalung iLA (Novalung, Alemania) y membrana Affinity
capaz de sustituir más de un 50% de la necesidad ventila-
NT (Medtronic, Minneapolis, MN, EE. UU.): se consigue la
toria y, por tanto, permite disminuir los requerimientos de
eliminación de CO2 y oxigenación parcial mediante la colo-
ventilación minuto convencional. Las membranas que per-
cación percutánea o quirúrgica (preferiblemente) de una
miten el intercambio gaseoso se componen generalmente
cánula que no ocupe más del 70% de la luz del vaso (usual-
de fibras huecas de material biocompatible (poli-4-metil-1-
22 mente en la arteria femoral) y otra cánula en una vena de
penteno) con una superficie de intercambio que va de 0,6
2 gran calibre. Para su funcionamiento el gradiente debe ser
a 2,5 m y en algunos casos están recubiertas de heparina
mayor o igual a 60 mmHg y, por tanto, requiere de cierto
u otros compuestos para mejorar la biocompatibilidad. La
grado de estabilidad hemodinámica por parte del paciente.
diferencia técnica fundamental con la ECMO es el reducido
flujo sanguíneo que emplea (entre 300-500 ml/min), que es
suficiente para la eliminación de la mayoría del CO2 pro- Dispositivos venovenosos
ducido por el metabolismo, todo ello gracias a la mayor
21 ®
solubilidad y cinética lineal de este gas en plasma . La Novalung iLA Activve (Novalung, Alemania): utiliza la
®
ventaja fundamental de usar una menor velocidad de flujo misma membrana iLA descrita anteriormente,pero inte-
de sangre es que permite usar cánulas de menor calibre y grada en una consola con una bomba diagonal capaz de
posibilita un mejor control de la anticoagulación. trabajar en un amplio rango de flujos (0,5-4,5 l/min), lo que
Esta eliminación eficiente del CO2 permitiría, con escasos permite administrar todo el espectro de soporte ventilato-
riesgos, reducir las necesidades de ventilación mecánica y rio extracorpóreo desde ECCO2R de bajo flujo hasta ECMO
disminuir la hipercapnia, evitando sus efectos en el sistema venovenosa.
®
nervioso central, en el corazón derecho y otros ya descritos DecapSmart (Hemodec, Salerno, Italia): se trata de
previamente. un dispositivo con bomba de rodillo, que utiliza una
Las cánulas que se pueden usar varían entre 13-17 Fr membrana de oxigenación y un hemofiltro en serie. El ultra-
de calibre y su colocación suele realizarse a pie de cama filtrado del hemofiltro es reincorporado a la circulación
mediante la técnica de Seldinger. Por su parte, gracias antes de la membrana, produciendo un efecto de recircula-
a la experiencia técnica acumulada con la ECMO, las ción del plasma con el objeto de conseguir una eliminación
bombas de sangre también han visto grandes avances, per- adicional del CO2 disuelto en él. Asimismo, permite el uso de
mitiendo disponer de bombas electromagnéticas donde el anticoagulación similar a la de los dispositivos de reemplazo
calor y el trauma mecánico se minimizan. También debemos renal.
Cómo citar este artículo: Romay E, Ferrer R. Eliminación extracorpórea de CO2: fundamentos fisiológicos y técnicos y
principales indicaciones. Med Intensiva. 2015. http://dx.doi.org/10.1016/j.medin.2015.06.001
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MEDIN-810; No. of Pages 6 ARTICLE IN PRESS
4 E. Romay, R. Ferrer
V-V ECCO2R (bombe de bajo flujo ProLung®/alto flujo iLA activve) V-V ECCO2R (Sistema integrado ALung®) V-V ECCO2R (Sistema integrado Decap®) A-V ECCO2R (Sistema iLA NovaLung®)
Bomba Bomba Aire Ultrafiltrado
Bomba Hemofiltro O2/Aire CO2 CO2
Aire
Aire Membrane Membrane Membrane Membrane
CO2 CO2
Figura 1 Esquema conceptual del funcionamiento de los diferentes dispositivos de remoción de CO2.
®
ProLUNG (Estor SpA, Pero, Italia): dispositivo similar al En el síndrome de distrés respiratorio
anterior, con la salvedad de no usar hemofiltro en su circuito
pero disponer de una membrana biocompatible no porosa de Los fundamentos de su uso en el síndrome de distrés respira-
2
poli-4-metil-1-penteno de 1,8 m , haciendo innecesaria la torio (SDRA) en gran parte han sido extrapolados de estudios
recirculación. Dispone, además, de un monitor que regula con ECMO. Los estudios que evalúan el uso del ECCO2R en el
el flujo de aire administrado y mide la eliminación de CO2 SDRA son heterogéneos, utilizando diferentes dispositivos,
®
de forma digital (ProLUNG Meter ). disenos˜ y desenlaces primarios. Los diferentes estudios eva-
®
Hemolung (Alung Technologies, Pittsburgh, EE. UU.): a lúan el uso de la ECCO2R como adyuvante de la ventilación
diferencia de los anteriores, este dispositivo utiliza un car- protectora, e incluso lo que se ha denominado ventilación
tucho donde están integradas la bomba y la membrana. El «ultraprotectora».
núcleo central rota acelerando radialmente la sangre hacia Terragni et al. realizaron un pequeno˜ estudio con
la periferia, donde se encuentra la membrana que, a pesar 32 pacientes con SDRA de menos de 72 h. Seleccionaron a
2
de ser de 0,67 m , tiene similar eficiencia en la eliminación los pacientes que a pesar de realizar ventilación protectora,
de CO2 que los dispositivos descritos previamente. presentaban Pplat entre 28 y 30 cmH2O, por lo que se les
®
Pump-Assisted Lung Protection o PALP (Maquet, Ras- bajó el Vc a 4 ml/Kg y se les conectó a la ECCO2R. En el
tatt, Alemania): sistema compacto que incluye la consola, mencionado grupo se pudieron alcanzar Pplat de 25 cmH2O
la bomba y la membrana en un solo equipo de reducidas con PEEP más alta y se demostró una reducción de citocinas
® 19
dimensiones (CardioHelp ), lo que le confiere la capacidad proinflamatorias en el lavado broncoalveolar , demos-
de ser muy portátil. Además, permite cambiar la membrana trando un efecto biológico que evidencia un menor dano˜
convencional por una disenada˜ para ECMO completa para inducido por el ventilador. Con un enfoque similar, el estu-
20
traslados. dio Xtravent comparó de forma aleatorizada la ventilación
La eliminación del CO2 por parte de los distintos equipos protectiva (6 ml/Kg de peso ideal) frente a la ultraprotec-
vendrá determinada principalmente por el flujo sanguíneo tiva (3 ml/Kg de peso ideal) + ECCO2R. En un análisis post hoc
promedio y, en menor medida, por el flujo de aire y la super- del subgrupo de enfermos con PaO2/FiO2 < 150 mmHg, el tra-
ficie y tiempo de contacto con la membrana. Por tanto, una tamiento con ventilación ultraprotectora + ECCO2R redujo
correcta colocación del catéter es fundamental a la hora significativamente los días libres de ventilación mecánica.
de optimizar el tratamiento, evitar problemas de coagu- Se observaron complicaciones de tipo hemorrágico o loca-
lación de las membranas y lograr la mayor eficiencia del les de las cánulas vasculares en un 7,5% de los enfermos en
tratamiento. tratamiento con ECCO2R; en este caso se utilizó la técnica
arteriovenosa.
La ECCO2R integrada en un circuito de diálisis demostró
Evidencia para su uso una reducción del uso de vasopresores y una mejoría de la
acidosis en pacientes con fallo renal y respiratorio en su
25
Diversos estudios experimentales demostraron que la mayoría debido a neumonía viral .
23,24 26
ECCO2R es factible, eficaz y segura técnicamente . Con Finalmente, una reciente revisión sistemática que
base en los resultados de los estudios experimentales, se ha incluyó 14 estudios (2 estudios aleatorizados controlados
planteado el uso de las técnicas de ECCO2R en el soporte y 12 observacionales) no encontró globalmente diferencias
ventilatorio en situaciones clínicas donde puede ser de uti- en la mortalidad, estancia en UCI o días libres de ventilación
lidad, como el SDRA y la agudización de la EPOC. mecánica, excepto en el subgrupo de los más graves. En
Cómo citar este artículo: Romay E, Ferrer R. Eliminación extracorpórea de CO2: fundamentos fisiológicos y técnicos y
principales indicaciones. Med Intensiva. 2015. http://dx.doi.org/10.1016/j.medin.2015.06.001
+Model
MEDIN-810; No. of Pages 6 ARTICLE IN PRESS
Eliminación extracorpórea de CO2: fisiología, técnicas e indicaciones 5
cuanto a seguridad, se observa una progresiva reducción del anterior, la usaron en un grupo de pacientes con hipercap-
número de complicaciones. En las técnicas arteriovenosas, nia con importante riesgo de requerir intubación. Además,
la complicación más frecuente fue la isquemia de la extre- incluyeron en otra rama pacientes que hubiesen tenido 2
midad donde estaba la cánula arterial, siendo grave en 6 intentos fallidos de destete de la VMNI y que no querían
casos (5 síndromes compartimentales y una amputación). ser intubados, y un tercer grupo de pacientes con ventila-
En las técnicas venovenosas, la complicación más frecuente ción invasiva en los que se evaluaría la ECCO2R en aquellos
fue la coagulación de la membrana/circuito del dispositivo. que no se podían destetar. Tanto en el primer como en el
En ambos casos los pacientes asignados a ECCO2R tuvieron segundo grupo se evitaron las intubaciones y la ventilación
mayores necesidades transfusionales. invasiva. En el tercer grupo se disminuyó el grado de dis-
Actualmente están en marcha diversos estudios para nea y el grado de soporte ventilatorio, permitiendo destetar
determinar la utilidad clínica de los dispositivos de ECCO2R satisfactoriamente a 3 de 11 pacientes.
32
combinados con la ventilación ultraprotectora (como el Más recientemente, Del Sorbo et al. realizaron un estu-
estudio SUPERNOVA, promovido por la European Society of dio clínico similar (cohorte pareada) en el que al grupo de
Intensive Care Medicine), sin embargo, la evidencia disponi- intervención se les realizó VMNI más ECCO2R venovenosa.
ble hasta la fecha no es concluyente y el uso de esta terapia Se observó que el riesgo de ser intubado aumentaba 3 veces
en el SDRA debe ser individualizada, basándose en criterios en los pacientes con VMNI sola comparativamente con los
fisiológicos y clínicos. que la acompanaban˜ de ECCO2R. Sin embargo, la diferencia
encontrada no fue significativa. La complicación asociada
más frecuente a la ECCO2R fue la coagulación del circuito,
En la enfermedad pulmonar obstructiva crónica tal como se ha reportado en otros estudios. agudizada
Otras indicaciones
Las exacerbaciones de la enfermedad pulmonar obstruc-
tiva crónica (EPOC) son la causa más importante de ingreso
Existe experiencia clínica en el uso de la ECCO2R en pacien-
hospitalario de estos pacientes y pueden presentarse en
tes con fístula broncopleural, disfunción primaria del injerto
diversas oportunidades en cortos periodos de tiempo (tem-
en el trasplante pulmonar, hipertensión intracraneal e hiper-
porada invernal). Si bien en su mayoría pueden ser tratadas
capnia, y otras situaciones clínicas donde la fisiopatología
médicamente, en ocasiones puede necesitarse la utilización
evidencia un potencial beneficio de la ECCO2R. Sin embargo,
de soporte ventilatorio tanto no invasivo (VMNI) como inva-
no deja de tratarse de un uso anecdótico, sin suficiente
sivo según la gravedad y los síntomas predominantes. Así
experiencia clínica acumulada.
pues, a una fracción de estos pacientes, a pesar de no pre-
sentar grandes cambios en la oxigenación o en los síntomas,
la exacerbación les lleva en ocasiones a la retención de CO2, Conclusiones
con las inevitables consecuencias que ello implica a nivel
del SNC. Además, cada exacerbación constituye un factor
Los avances técnicos de los últimos anos˜ han permitido que
de riesgo para nuevas exacerbaciones, con un aumento de
la ECCO2R sea simple y factible, y se ha posicionado como
27
la mortalidad . La mortalidad de los pacientes con exacer-
una herramienta más para el soporte de los pacientes con
baciones de EPOC ronda el 4,8% en pacientes con VMNI,
enfermedades respiratorias graves y alta mortalidad. Es una
28
reportado por Lindenauer et al. , y el 29,3% en aquellos
opción terapéutica que se sitúa entre el soporte ventilato-
29
que fracasan con la VMNI y pasan a ventilación invasiva .
rio convencional y el soporte respiratorio total (ECMO), y
A pesar de los avances en la aplicación y refinamiento de
por tanto, consideramos que su lugar en la práctica podría
los protocolos de uso de la VMNI, aún existe un porcentaje
encontrarse en el nicho de pacientes con SDRA con una
importante de pacientes (19-40%) que fracasan y requieren
PaO /FiO > 80 y < 150 mmHg, en los que ya se haya optimi- 30 2 2
ser intubados .
zado el tratamiento y soporte con ventilación convencional
Es en 2012 cuando se publica el primer estudio clínico
al máximo, y en los que se considere oportuno disminuir
sobre la seguridad y eficacia del uso de la ECCO2R en
al mínimo la distensión pulmonar y/o atenuar los efectos
31
pacientes con insuficiencia respiratoria hipercápnica . Se
de la hipercapnia y la acidosis, para lo cual ha probado ser
trata de un estudio retrospectivo, multicéntrico, en el que
efectiva. Asimismo, para los pacientes con EPOC agudizada
a 21 pacientes con hipercapnia agudizada se les instauró
que no tengan indicación de intubación o en los que la VMNI
tratamiento con ECCO2R arteriovenosa antes del fracaso
esté contraindicada, la ECCO2R constituye una nueva opción
de la VMNI, definido este como la necesidad de intubar
terapéutica que ha de considerarse de forma individualizada
al enfermo. Este grupo de pacientes fue luego comparado
en coherencia con la relación riesgo/beneficio.
con una cohorte retrospectiva de pacientes que requerían
Por su menor tasa de complicaciones, consideramos las
ventilación invasiva. El 90% de los pacientes del grupo de
técnicas venovenosas las más adecuadas. Sin embargo, la
intervención no requirió ventilación invasiva. Sin embargo,
ECCO2R dista aún de ser la solución definitiva o el dispositivo
no se demostraron diferencias en la mortalidad. En cuanto
perfecto, y sus efectos sobre indicadores clínicos aún están
a las complicaciones, se informa de 2 sangrados mayores y
por determinarse.
7 menores durante el curso del tratamiento, un seudoaneu-
risma femoral y un paciente con trombocitopenia inducida
por heparina. Conflicto de intereses
6
Asimismo, Burki et al. realizaron un estudio piloto en
el que utilizaron ECCO2R venovenosa y, como en el estudio No hay conflicto de intereses.
Cómo citar este artículo: Romay E, Ferrer R. Eliminación extracorpórea de CO2: fundamentos fisiológicos y técnicos y
principales indicaciones. Med Intensiva. 2015. http://dx.doi.org/10.1016/j.medin.2015.06.001
+Model
MEDIN-810; No. of Pages 6 ARTICLE IN PRESS
6 E. Romay, R. Ferrer
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Cómo citar este artículo: Romay E, Ferrer R. Eliminación extracorpórea de CO2: fundamentos fisiológicos y técnicos y
principales indicaciones. Med Intensiva. 2015. http://dx.doi.org/10.1016/j.medin.2015.06.001
EXACERBACIÓN EPOC Extracorporeal CO2 Removal: The Minimally Invasive Approach, Theory, and Practice
Eleonora Duscio, MD1; Francesco Cipulli, MD1; Francesco Vasques, MD1; Francesca Collino, MD1; Francesca Rapetti, MD1; Federica Romitti, MD1; Tim Behnemann, MS1; Julia Niewenhuys, MS1; Tommaso Tonetti, MD1; Iacopo Pasticci, MD1; Francesco Vassalli, MD1; Verena Reupke, DVM2; Onnen Moerer, MD1; Michael Quintel, MD1; Luciano Gattinoni, MD1
Objectives: Minimally invasive extracorporeal CO2 removal is an ylpentene membrane, filling volume 125 mL) through a 13F cath- co accepted supportive treatment in chronic obstructive pulmonary eter. V 2ML was measured under different combinations of inflow co disease patients. Conversely, the potential of such technique in P 2 (38.9 ± 3.3, 65 ± 5.7, and 89.9 ± 12.9 mm Hg), extracorpo- treating acute respiratory distress syndrome patients remains to real blood flow (100, 200, 300, and 400 mL/min), and gas flow co co be investigated. The aim of this study was: 1) to quantify mem- (4, 6, and 12 L/min). At each setting, we measured V 2ML, V 2NL, co brane lung CO2 removal (V 2ML) under different conditions and lung mechanics, and blood gases. co co 2) to quantify the natural lung CO2 removal (V 2NL) and to what Measurements and Main Results: V 2ML increased linearly with co extent mechanical ventilation can be reduced while maintaining extracorporeal blood flow and inflow P 2 but was not affected co co co co by gas flow. The outflowco P was similar regardless of inflow total expired CO2 (V 2tot = V 2ML + V 2NL) and arterial P 2 2 co co constant. P 2 and extracorporeal blood flow, suggesting that V 2ML was Design: Experimental animal study. maximally exploited in each experimental condition. Mechanical Setting: Department of Experimental Animal Medicine, University ventilation could be reduced by up to 80–90% while maintaining co of Göttingen, Germany. a constant Pa 2.
Subjects: Eight healthy pigs (57.7 ± 5 kg). Conclusions: Minimally invasive extracorporeal CO2 removal
Interventions: The animals were sedated, ventilated, and removes a relevant amount of CO2 thus allowing mechanical ven- connected to the artificial lung system (surface 1.8 2m , polymeth- tilation to be significantly reduced depending on extracorporeal co blood flow and inflow P 2. Extracorporeal CO2 removal may provide the physiologic prerequisites for controlling ventilator- 1Department of Anesthesiology, Emergency and Intensive Care Medicine, induced lung injury. (Crit Care Med 2018; XX:00–00) University of Göttingen, Göttingen, Germany. Key Words: acute respiratory distress syndrome; carbon dioxide 2Department of Experimental Animal Medicine, University of Göttingen, Göttingen, Germany. removal; extracorporeal carbon dioxide removal; extracorporeal This experiment has been performed at the Department of Experimental membrane oxygenation; minimally invasive extracorporeal life Animal Medicine, University of Göttingen, Göttingen, Germany. support; ventilator-induced lung injury Supplemental digital content is available for this article. Direct URL cita- tions appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ ccmjournal). n 1977, we described extracorporeal CO removal (ECCO R) Supported, in part, by departmental funding. 2 2 as a tool for attenuating high pressure/high volume mechani- Drs. Eleonora’s, V. Francesco’s, C. Francesca’s, R. Francesca’s, Fed- erica’s, Behnemann’s, Niewenhuys’s, Pasticci’s, Vassalli’s, and Luciano’s Ical ventilation in low compliance respiratory systems (1–7). institutions received funding from Estor, and they disclosed that Estor In the wake of the influenza H1N1 epidemic (8) and the Con- (Pero, Milan, Italy) and Dimar (Medolla, Modena, Italy) provided the mate- ventional ventilatory support vs extracorporeal membrane rial for the experiment. Dr. Onnen’s institution received funding from a workshop on hemodynamics supported in part by Pulsion. Dr. Michael’s oxygenation for severe adult respiratory failure (CESAR) trial institution received funding from Estor, and he received funding from (9), venovenous extracorporeal lung support has acquired an Xenios/Fresenius (consultant), Baxter (consultant), Sphere Medical, and important role in the treatment of severe respiratory failure. Faron (member of the steering committee). The remaining authors have disclosed that they do not have any potential conflicts of interest. The extracorporeal support includes both supplying oxygen For information regarding this article, E-mail: [email protected] (extracorporeal membrane oxygenation [ECMO]) and remov-
Copyright © 2018 by the Society of Critical Care Medicine and Wolters ing CO2 from the venous blood (ECCO2R). In the absence of co Kluwer Health, Inc. All Rights Reserved. an artificial lung, expired CO2 (V 2) and oxygen consumption o DOI: 10.1097/CCM.0000000000003430 (V 2) are strictly related according to the metabolic respiratory
Critical Care Medicine www.ccmjournal.org 1 Copyright © 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. Duscio et al
co o 2 quotient (R = V 2/V 2). At equilibrium, this ratio can vary cartridge (ProLUNG, surface area 1.8 m , polymethylpen- between 0.7 and 1. The addition of an artificial lung enables a tene membrane, filling volume 125 mL; Euroset, Medolla, dissociation of oxygenation from CO2 removal. Indeed, as an Modena, Italy), a roller pump (ESTORflow; Medica, Medolla, example, most of the CO2 can be removed by an artificial lung Modena, Italy), and its circuit. Anticoagulation was provided while most of the oxygen is delivered through the natural lung. by the continuous infusion of unfractionated heparin to The opposite is also true, depending on the extracorporeal maintain the activated clotting time at about 300 seconds. blood and gas flows settings and on the mechanical ventilation This target was chosen to avoid possible thrombotic events setting (for details, see supplemental materials, Supplemental during the experiments as porcine blood coagulates more Digital Content 1, http://links.lww.com/CCM/E33). A recent co readily than that of humans (11, 12). V 2ML was measured position paper referred to ECMO as a technique for provid- through a side-stream device (ProLung Meter; Estor, Pero, ing oxygenation and CO2 removal at high blood flow, and to Milan, Italy). Animals were ventilated with an Avea ventila- ECCO R as a technique for removing CO at low extracorpo- co 2 2 tor (Vyaire Medical, Mettawa, IL), and V 2NL was measured real blood flow (ECBF) (10). by the Di-CO2R system (DIMAR, Medolla, Modena, Italy). CO removal depends on several factors, that is, the artifi- co co co 2 V 2tot was the sum of V 2NL plus V 2ML. The natural and cial lung surface area and its specific features, the coP of the o o o 2 membrane lung V 2 (V 2NL∙V 2ML) were computed with the venous blood entering the artificial lung, and the extracorpo- Fick equation. real flows of blood and gas. At equilibrium, that is, at a constant co co arterial P 2, membrane lung CO2 removal (V 2ML) plus the Experimental Design natural lung CO removal (Vco ) equals the CO produced 2 2NL 2 The experimental animals underwent ECCO2R at three set lev- by the metabolism (Vco = Vco + Vco ). Therefore, co 2tot 2ML 2NL els of Pa 2 (30, 55, and 80 mm Hg), four ECBF rates (100, co increasing V 2ML allows a corresponding decrease in alveolar 200, 300, and 400 mL/min), and three gas flow rates (4, 6, and co co 2 ventilation by an extent that depends on the V 2ML/V 2tot 12 L/min/1.8 m ). In seven pigs, we tested two artificial lungs in ratio. The rational use of ECCO2R to allow adjustments of the parallel. In each combination of extracorporeal gas and blood mechanical ventilation requires knowledge of both the Vco co 2ML flow, artificial lung surface, and Pa 2, we aimed at maintaining and the Vco . Unfortunately, most of the available ECCO R co co 2NL 2 V 2tot constant by compensating any change in V 2ML with an or ECMO devices have no provisions for measuring either co appropriate change in V 2NL by modifying minute ventilation. Vco or Vco . In this study, we tested a minimally invasive co 2ML 2NL Measurements were taken 15 minutes after the set Pa 2 was ECCO2R device, the ProLung system (Estor, Pero, Milan, Italy). reached (Fig. S1, Supplemental Digital Content 1, http://links. The goal was to 1) define the coV under different conditions co 2ML lww.com/CCM/E33). The time to reach the set Pa 2 averaged of extracorporeal blood and gas flows, membrane surface, and 34.9 ± 24.9 minutes. co inflow P 2 and 2) measure to what extent we were able to co decrease V 2NL and mechanical ventilation, whereas main- Outcome Measures taining a constant arterial Pco under each condition. All this 2 At each ECCO2R step, we measured the following variables: would clarify whether the minimally invasive ECCO2R would “Gas exchange”: arterial, central venous and mixed venous provide the physiologic prerequisites for being considered for co blood gases, end-tidal CO2, dead space, shunt fraction, V 2NL, use even in severe adult respiratory distress syndrome (ARDS). o and V 2NL; “Hemodynamics”: arterial, central venous and pul- monary pressures, cardiac output, and urine output; “Lung MATERIALS AND METHODS mechanics”: functional residual capacity (only at baseline), The experiments were performed after ethical committee minute volume and alveolar ventilation, airways peak pressure, approval in eight female domestic pigs (57.7 ± 5 kg) under gen- airways and esophageal plateau, and end-expiratory pressures eral anesthesia in the supine position. The animals were instru- (PEEP) pressures, mechanical power (13), transpulmonary mented with an endotracheal tube, esophageal balloon, and pressure, driving pressure, chest wall, lung and respiratory central venous, pulmonary artery, femoral artery, and urinary system elastances; “Extracorporeal variables”: extracorporeal catheters. An electrolyte solution (Sterofundin 1/1; B. Braun blood and gas flow, inflow and outflow pressures, inflow and co o Melsungen, Melsungen, Germany) was infused at 2–3 mL/kg/ outflow blood gases,V 2ML, and V 2ML. hr during the entire experiment. Whenever necessary, colloids (Gelafundin 4%) and norepinephrine were administered in Statistical Analysis order to maintain the mean arterial pressure above 60 mm Hg. Data are reported as means and sds. In the figures, we used the se co co co For details, see supplementary materials (Supplemental Digital for sake of clarity. The V 2tot and the V 2ML/V 2tot were also Content 1, http://links.lww.com/CCM/E33). grouped in tertiles. We used the analysis of variance test with Tukey adjustment to compare groups. Student t test was used Extracorporeal Setting and Measurements when appropriate. A p value of less than 0.05 was considered A 13F double lumen catheter (Joline; JOLINE GmbH & Co. statistically significant. Linear regression was used to assess the co co KG, Hechingen, Germany) was inserted into a femoral vein, association between V 2ML and inflow P 2, blood flow and gas and ECCO2R was performed with the ProLung System (Estor, flow. Statistical analysis was performed using R software (The R Pero, Milan, Italy). This device consisted of a hemoperfusion Foundation for Statistical Computing, Vienna, Austria).
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RESULTS parallel and keeping all the other variables constant (91.6 ± 32 co The measured values of arterial P 2 for the targeted val- to 104.91 ± 44 mL/min; p = 0.06) (Table S1, Supplemental ues of 30, 55, and 80 mm Hg were 30.9 ± 2.6, 55 ± 4.8, and Digital Content 1, http://links.lww.com/CCM/E33). co co co 81.3 ± 9.3 mm Hg, respectively, corresponding to inflow In Figure 3A, we show V 2ML/V 2tot as a function of V 2tot co P 2 values in the artificial lung of 38.9 ± 3.3, 65 ± 5.7, and (artificial + natural lung). For sake of clarity, in Figure 3B, co co co 89.9 ± 12.9 mm Hg, respectively. V 2ML/V 2tot is plotted as a function of quintiles of V 2tot. As co co co co co In Figure 1, we show V 2ML as a function of inflow P 2 shown, V 2ML/V 2tot was a function V 2tot, and it was highly at ECBF rates ranging from 100 to 400 mL/min (Fig. 1A). In variable. In Figure 4, we show minute ventilation as a function co co co Figure 1B, we show V 2ML as a function of ECBF at the set of V 2ML/V 2tot. As shown, to maintain the targeted arterial co co P 2 values of 30, 55, and 80 mm Hg. As shown, in this mini- P 2, minute ventilation was reduced in a manner proportional co co co mally invasive ECCO2R, V 2ML increased linearly both with to V 2ML/V 2tot. For a given ECBF rate, the latter, in turn, co inflow P 2 and ECBF, ranging from a minimum of 12.4 mL/ depended on the degree of hypercapnia. As an example, in these min up to 171 mL/min. healthy animals, the minute ventilation of 12 L/min applied to co maintain the set Pco of 30.9 ± 2.6 mm Hg could be reduced up V 2ML did not change when gas flow was increased from 2 4 to 6 and 12 L/min (p = 0.59) (Fig. S2, Supplemental Digital to 1.51 L/min or even below 1L/min if one was willing to accept co Content 1, http://links.lww.com/CCM/E33). This indicated an increase in P 2 levels to 55 or 80 mm Hg, respectively. 2 co co that the use of a 1.8 m polymethylpentene lung surface and In Table 1, we grouped the V 2ML/V 2tot in tertiles defined co as low (up to 26.6%) moderate (up to 50.2%), and high (up gas flow of 4 L/min already gave maximal V 2ML at any combi- co to 98.9%), and we show its association with metabolic, gas nation of ECBF and inflow P 2. Indeed, as shown in Figure 2, co exchange, hemodynamics, and respiratory variables. Arterial outflow P 2 was similar between the three levels of inflow co co and venous oxygenation were kept constant by a mild increase P 2 (p = 0.074). When ECBF, inflow P 2 and gas flow were analyzed by multivariate regression, only ECBF and inflow in PEEP to keep the mean airway pressure constant when min- co io P 2 were significantly and independently associated with ute ventilation was decreased, and by an increase in F 2, to co o V 2ML according to equation 1: keep alveolar P 2 constant when the respiratory quotient of the natural lung was decreased (14). The hemodynamic variables remained within a normal range despite a significant decrease VCOm L/min= 229 ECBF L/min+ 0.71 inflow 2ML ( ) ××( ) in cardiac output, primarily due to a decreased heart rate. No co PCO2 (mm Hg)− 31.14 signs of tissues hypoxia were noted. The extent of the V 2ML/ co V 2tot ratio allowed a marked change in the respiratory vari- ()Rp2 =0.79; <0.001 ables. Indeed, we were able to reduce minute ventilation from a baseline value of 7.4 L/min to 1.9 L/min, and the mechani- co V 2ML did not change significantly when the lung surface cal power, a comprehensive variable of ventilator-induced lung was increased from 1.8 to 3.6 m2 by adding another lung in injury determinants, from 9.3 to 2.6 J/min.
co co Figure 1. Membrane lung CO2 removal (V 2ML) as a function of CO2 partial pressure in the blood entering the membrane lung (inflow P 2) at different co extracorporeal blood flow (ECBF) rates (A) and as a function of ECBF at different targeted arterial CO2 partial pressure (set Pa 2) levels (B). co co 2 co co 2 A, V 2ML = 1.08 × inflowP 2 + 39.6, R = 0.62 (ECBF 400 mL/min); V 2ML = 0.89 × inflow P 2 + 39.7, R = 0.74 (ECBF 300 mL/min); co co 2 co co 2 V 2ML = 0.64 × inflow P 2 + 27.38, R = 0.55 (ECBF 200 mL/min); V 2ML = 0.44 × inflow P 2 + 11,9, R = 0.53 (ECBF 100 mL/min). B, co 2 co co 2 co co V 2ML = 0.3 × ECBF + 24.81, R = 0.84 (set Pa 2 80 mm Hg); V 2ML = 0.20 × ECBF + 25.76, R = 0.58 (set Pa 2 55 mm Hg); V 2ML = 0.19 × 2 co ECBF + 12.2, R = 0.73 (set Pa 2 30 mm Hg).
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power from 9.3 to 2.6 J/min with no detectable drawbacks (Table 1). co co V 2ML depends on several factors, namely inflow P 2, extracorporeal blood and gas flows, and membrane lung char- acteristics, that is, gas diffusion coefficient and surface area (3). Typically, during high-flow venovenous extracorporeal support, co V 2ML increases linearly with gas flow and logarithmically with co blood flow for a given inflow P 2 (3). Yet in our study on low- co flow venovenous ECCO2R, the V 2ML was independent from gas flow, whereas it increased linearly with ECBF. In our experimen- co tal setting, inflow P 2 and ECBF were the primary determinants co of V 2ML, which was not affected by increasing gas flow above 4 L/min. Of note, however, the artificial gas/blood flows ratios we implemented were always remarkably elevated, ranging from a minimum of 30 to a maximum of 40. This suggests that, as far co as the gas flow is concerned, V 2ML was already maximal with 2 co the single 1.8 m lung, as indicated by similar outflow P 2 levels, co regardless of inflow P 2 or blood flow (Fig. 2). Therefore, within the range of our study variables (blood flow rate 100–400 mL/min co co Figure 2. Membrane lung CO2 partial pressure in blood entering the and inflow P 2 30–80 mm Hg), outflow P 2 was close to its co membrane lung (inflow P 2) (x-axis, left) and CO2 partial pressure in co asymptote. However, doubling the lung surface increased V 2ML co blood leaving the membrane lung (outflow P 2) (x-axis, right) at the three co by about 14%. This was likely due to a 100 % increase in transit targeted arterial CO2 partial pressure (set Pa 2) levels tested in all the co co co conditions of blood flow, gas flow, and surface (*set Pa 2 30; †set Pa 2 time which gave a small but significant decrease in outflow P 2 55; ‡set Paco 80 mm Hg). 2 from 10 to 7 mm Hg. In these experiments, we used animals weighing 57 kg to DISCUSSION simulate small adult humans. The degree of adjustment of The main result of this study was that a considerable amount co co mechanical ventilation depends on the V ML/V 2tot ratio of CO was removed by the Estor ProLung system using only co co 2 attained. TheV 2ML is a function of inflow P 2 and ECBF, a minimally invasive cannulation and a blood flow rate simi- co co co whereas the V 2tot (V 2ML + V 2NL) depends also on the co lar to that used in renal dialysis. Accepting a Pa 2 of 74 mm ventilator settings and the metabolic CO2 production. In our
Hg and pH 7.3, we were able to remove up to 138.8 mL/min experiments, during the CO2 removal, the metabolic activity o of CO2. This allowed us to reduce total ventilation from 7.4 remained constant (Table 1) (V 2 ~150 mL/min). This indicates co co co to 1.9 L/min with a corresponding reduction in mechanical that the V 2ML/V 2tot were primarily function of the V 2ML.
co co co co co co co Figure 3. A, V 2ML/V 2tot percentage (V 2ML/V 2tot) as a function of total CO2 removal (V 2ML + V 2NL) (V 2tot). B, Same data are represented grouped co se –0.005x 2 –0.005x 2 co co in V 2tot quintiles, bars represent . A, y = 108.81e , R = 0.44. B, 114.19e , R = 0.97. V 2NL = natural lung CO2 removal, V 2ML = membrane lung CO2 removal.
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co co Figure 4. A, Minute ventilation (Ve) at the three targeted arterial CO2 partial pressure (set Pa 2) levels tested in the experiment as a function of V 2ML/ co co co –0.029x 2 co co co co se V 2tot percentage (V 2ML/V 2tot) (y = 12.75e , R = 0.76). B, Ve as a function of V 2ML/V 2tot grouped in V 2ML/V 2tot quintiles, bars represent –0.022x 2 co (y = 11.91e , R = 0.92). V 2ML = membrane lung CO2 removal.
Indeed, the appropriate combination of ECBF and hyper- reported previously (15–18) due to the larger surface area of co capnia, the determinants of V 2ML, made possible that in some the membrane lung. Although polymethylpentene membrane co animals the artificial lung removed nearly 100% of the V 2tot lungs are associated with a lower consumption of clotting fac- (Fig. 3). It is worth remembering that, the removal of 50% of tors (20), there may still be a slight risk of stasis and clotting co the V 2tot by the membrane lung, which can be achieved with with the low flow rate over a large membrane surface area. In the device used in this study, allows a reduction of total ven- these short-term experiments with the targeted activated clot- tilation by up to 70%. Obviously, the mechanical power act- ting time of 300 seconds, we observed neither clotting in the ing on the lung, which includes all the components of possibly system nor any decrease in its performance, nor any hemor- injurious mechanical ventilation, can be reduced by the same rhagic complications. However, these results can obviously not fraction. The extent at which the mechanical ventilation may be directly translated to the clinical setting. be reduced, may be estimated by using the equation 1 which The present indications for ECCO2R with ECBFs of less co gives a first approximation of the V ML that may be reached than 0.5 L/min, as recently reviewed by Camporota et al (21) by applying the minimally invasive technique. refer mainly to the treatment of uncontrolled hypercapnia in Our results compare favorably with those of previous stud- chronic obstructive pulmonary disease, where this technique ies, conducted with similar blood flow rates and catheter sizes. is largely accepted, whereas there are few studies on its use as a Indeed, using an artificial lung with a surface area of 0.32 2m , bridge to lung transplant and as a support in thoracic surgery. co Godet et al (15) reported a V 2ML between 35 and 75 mL/min, However, there is still no indication for its use in severe ARDS, co whereas Livigni et al (16) who did not measure the V 2ML, primarily because this minimally invasive technique cannot co described a Pa 2 reduction of 20% from baseline (17). In correct the hypoxemia, which is the major concern in these another experimental setup using an artificial lung with a sur- patients (22, 23). Indeed, high-flow ECMO can provide up to 2 co face of 0.67 m , Turani et al (18) measured a V 2ML of 37– 100% of the oxygen demand, whereas ECCO2R can only pro- co co 56 mL/min, whereas Grasso et al (17) reported a V 2ML/V 2tot vide, at most, ca. 10 mL/min of oxygen. It must be underlined, of approximately 40% with a reduction in minute ventilation however, that ECCO2R can be employed to reduce the invasive- of about 50%. These values are lower than those observed in ness of ventilation and, thereby, the risk of ventilator-induced co our experiments, where the maximum V 2ML was 171 mL/min, lung injury, as shown by Terragni et al (24). co co and V 2ML/V 2tot approached 1.0 in some cases (Figs. 3 and 4). Therefore, it is very low oxygen delivery capacity is the main Zanella et al (19) using a blood flow of 250 mL/min, a membrane conceptual obstacle to using this minimally invasive technique 2 co lung surface of 1.8 m , an inflow P 2 of 60.9 mm Hg, associated even in severe ARDS. However, one may question whether intro- with a dialyser and a ventilation of acidified dialysate, reported a ducing a large amount of oxygen into the venous blood is the most co V 2ML of 86 mL/min compared with the 69.4 mL/min we com- rational way to treat these patients, and one may critically exam- puted using equation 1 with the same input conditions. ine what happens during high-flow ECMO, for which the hypox-
The volume of CO2 eliminated through the artificial lung emia is the primary indication (23). The introduction of a large in our study was probably larger than most of the volumes amount of oxygen during venovenous ECMO induces a sharp
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TABLE 1. Main Outcome Variables at Tertiles of Membrane Lung CO2 Removal/Membrane
Lung CO2 Removal Plus Natural Lung CO2 Removal
co co sd V 2ML/V 2tot, Mean ±
Baseline, Low Moderate High Variables Mean ± sd (6.8–26.6 %) (26.7–50.2 %) (52.6–98.9 %) p < 0.05
Observations, n 8 41 40 41 Natural lung oxygen supply (mL/min) 175 ± 30 152.3 ± 47 142.8 ± 52.3 149.9 ± 40.1 NS Membrane lung oxygen supply (mL/min) — 4.2 ± 2.98 5.46 ± 2.48 7.9 ± 2.63 a,b
co c,a,b V 2NL (mL/min) 306.2 ± 95 272.8 ± 60.5 150.3 ± 43.8 49.7 ± 33.6
co c,a,b V 2ML (mL/min) — 63.5 ± 19.4 93.3 ± 19.3 138.8 ± 31.6
co co c,a,b V 2ML/V 2tot (%) — 19 ± 5 39 ± 6 75 ± 14
co co c,a,b V 2ML + V 2NL (mL/min) 306.2 ± 95 336.3 ± 61.7 243.6 ± 54.5 188.5 ± 42.1 Hemoglobin (g/dL) 8.3 ± 1.5 6.5 ± 1.0 7.4 ± 0.8 7.2 ± 1.0 c,a
io a F 2 (%) 0.4 ± 0 0.49 ± 0.14 0.53 ± 0.15 0.6 ± 0.19
o Pa 2 (mm Hg) 198 ± 16 181.4 ± 72.4 188.4 ± 70.6 192 ± 97.8 NS Venous blood oxygen partial pressure (mm Hg) 52 ± 9 54.2 ± 9.7 54.5 ± 9.9 56.8 ± 11.2 NS
co c,a,b Pa 2 (mm Hg) 43.7 ± 3 44.5 ± 19.5 57.9 ± 21.4 74.2 ± 16.7 Arterial pH 7.49 ± 0.04 7.52 ± 0.15 7.43 ± 0.16 7.3 ± 0.1 c,a,b
c,a,b CO2 partial pressure in blood entering — 53.6 ± 19.8 69.6 ± 24.4 83.6 ± 17.3 the membrane lung (mm Hg)
CO2 partial pressure in blood leaving — 7.8 ± 2.9 8.1 ± 2.8 9.2 ± 3.5 NS the membrane lung (mm Hg) Cardiac output (L/min) 6.2 ± 1.5 7.4 ± 1.6 6.1 ± 1 5.9 ± 1.1 c,a Heart rate (beats/min) 64 ± 12 79 ± 18 71 ± 18 60 ± 15 a,b Mean systemic arterial pressure (mm Hg) 89 ± 11 81 ± 12 83 ± 13 77 ± 10 NS Central venous pressure (mm Hg) 8 ± 3 10 ± 3 9 ± 3 8 ± 3 c,a Mean pulmonary arterial pressure (mm Hg) 20 ± 6 21 ± 6 20 ± 5 22 ± 5 NS Mean occlusion pressure (mm Hg) 9.9 ± 5.4 11 ± 3 10 ± 3 9 ± 3 a Mixed venous blood oxygen saturation (%) 86 ± 5 89 ± 4 87 ± 4 81 ± 13 a,b Arterial lactate (mmol/L) 0.6 ± 0.3 0.4 ± 0.2 0.3 ± 0.2 0.3 ± 0.1 a Minute ventilation (L) 7.4 ± 0.7 7.7 ± 3 4.7 ± 2.4 1.9 ± 1.2 c,a,b Respiratory rate (breaths/min) 15 16 ± 5 11 ± 4 5 ± 3 c,a,b Tidal volume-pig weight ratio (mL/kg) 8.6 ± 0.7 8 ± 1.1 7.3 ± 1 6.2 ± 1.1 c,a,b Dead space fraction (%) 32 ± 8 38 ± 6 39 ± 8 48 ± 8 a,b
a Airways plateau pressure (cm H2O) 16.4 ± 1.6 17.9 ± 1.9 17.1 ± 1.6 16.3 ± 1.7 a,b Positive end-expiratory pressure (cm H2O) 5.0 ± 0.3 5.6 ± 1.2 5.7 ± 1.6 6.9 ± 1.3 Airways driving pressure 11.4 ± 1.6 12.4 ± 2.3 11.3 ± 2.7 9.4 ± 1.9 a,b
a Mean airway pressure (cm H2O) 9.1 ± 0.9 9.5 ± 0.9 9.1 ± 0.9 8.6 ± 1.0 Respiratory system mechanical power (J/min) 9.3 ± 1.7 11.2 ± 4.8 6.3 ± 3.5 2.6 ± 1.6 c,a,b
co co co co co co NS = not significant, V 2NL = natural lung CO2 removal, V 2ML = membrane lung CO2 removal, V 2ML/V 2tot = V 2ML/V 2tot percentage. aTertile 3 vs 1. bTertile 3 vs 2. cTertile 1 vs 2. co co The main outcome variables are here represented at baseline and among groups of equal count V 2ML/V 2tot tertiles. p values between tertiles (p < 0.05) are reported in the last column (Uniway-analysis of variance test with Tukey adjustment). Dashes indicate missing values.
6 www.ccmjournal.org XXX 2018 • Volume XX • Number XXX Copyright © 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. Clinical Investigation increase in mixed venous oxygen saturation and oxygen tension, 7. Gattinoni L, Kolobow T, Damia G, et al: Extracorporeal carbon dioxide which in turn has two effects, that is, a decrease in oxygen trans- removal (ECCO2R): A new form of respiratory assistance. Int J Artif Organs 1979; 2:183–185 fer throughout the natural lung, and the loss of hypoxic pulmo- 8. Davies A, Jones D, Bailey M, et al; Australia New Zealand Extracor- nary vasoconstriction (25–27), which is still functional in ARDS poreal Membrane Oxygenation Influenza Investigators: Extracorporeal (28). As a consequence, the increase in arterial oxygenation is due membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA 2009; 302:1888–1895 solely to the increased oxygen tension in the venous blood shunt- 9. Peek GJ, Clemens F, Elbourne D, et al: CESAR: Conventional ventila- ing throughout the natural lung. These mechanisms account for tory support vs extracorporeal membrane oxygenation for severe adult o respiratory failure. BMC Health Serv Res 2006; 6:163 the modest increase in Pa 2 that one observes immediately after high-flow ECMO is instituted: the oxygenation of venous blood 10. Conrad SA, Broman LM, Taccone FS, et al: The Extracorporeal life support organization maastricht treaty for nomenclature in extracor- is increased, but the loss of pulmonary vasoconstriction leads to poreal life support. A position paper of the extracorporeal life support a marked increase in right-to-left shunt. Therefore, the possible organization. Am J Respir Crit Care Med 2018; 198:447–451 o subsequent increase in Pa 2 is not necessarily due to the direct 11. Köstering H, Mast WP, Kaethner T, et al: Blood coagulation studies in effects of ECMO on oxygenation but to an improvement in domestic pigs (Hanover breed) and minipigs (Goettingen breed). Lab Anim 1983; 17:346–349 physiopathology due to the changes in the ventilatory conditions 12. Siller-Matula JM, Plasenzotti R, Spiel A, et al: Interspecies differences that ECMO makes possible (29). However, the same changes in in coagulation profile. Thromb Haemost 2008; 100:397–404 the ventilatory settings are possible due to the removal of CO2 13. Gattinoni L, Tonetti T, Cressoni M, et al: Ventilator-related causes of lung instead of the addition of oxygen to the venous blood. injury: The mechanical power. Intensive Care Med 2016; 42:1567–1575 Therefore, we may speculate that it is possible to consider 14. Gattinoni L, Kolobow T, Tomlinson T, et al: Control of intermittent posi- tive pressure breathing (IPPB) by extracorporeal removal of carbon the use of ECCO2R even in severe ARDS. Indeed, first of all, this dioxide. Br J Anaesth 1978; 50:753–758 technique allows one to reduce the invasiveness of mechanical 15. Godet T, Combes A, Zogheib E, et al: Novel CO2 removal device driven ventilation to the levels used during high-flow ECMO (30). by a renal-replacement system without hemofilter. A first step experi- Second, oxygenation is maintained via the natural lung as long mental validation. Anaesth Crit Care Pain Med 2015; 34:135–140 16. Livigni S, Maio M, Ferretti E, et al: Efficacy and safety of a low-flow as mean airway pressure is maintained when mechanical ven- veno-venous carbon dioxide removal device: Results of an experimen- tilation variables are reduced, for example, by increasing PEEP. tal study in adult sheep. Crit Care 2006; 10:R151 Third, hypoxic vasoconstriction remains unaltered without 17. Grasso S, Stripoli T, Mazzone P, et al: Low respiratory rate plus mini- any increase in right-to-left shunt and, finally, the advantages mally invasive extracorporeal Co2 removal decreases systemic and pulmonary inflammatory mediators in experimental acute respiratory of this minimally invasive approach consist in its being easy to distress syndrome. Crit Care Med 2014; 42:e451–e460 implement (double lumen 13F single cannula), easy to moni- 18. Turani F, Martini S, Marinelli A, et al: ECCO2 removal with a phosphor- tor and likely requiring an anticoagulation similar to that used ylcholine-coated membrane oxygenator in difficult respiratory weaning in hemodialysis, including the possibility of regional antico- patients. Critical Care 2013; 17(Suppl 2):P129 19. Zanella A, Mangili P, Giani M, et al: Extracorporeal carbon dioxide agulation (31, 32). removal through ventilation of acidified dialysate: An experimental study. J Heart Lung Transplant 2014; 33:536–541 20. Khoshbin E, Roberts N, Harvey C, et al: Poly-methyl pentene oxygen- ACKNOWLEDGMENTS ators have improved gas exchange capability and reduced transfusion We thank Estor (Pero, Milan, Italy) for providing the ProLung requirements in adult extracorporeal membrane oxygenation. ASAIO system and Dimar (Medolla, Modena, Italy) for providing the J 2005; 51:281–287 DI-CO2 system. We are grateful to Ms. Charlotte Munz for her 21. Camporota L, Barrett N: Current applications for the use of extracor- poreal carbon dioxide removal in critically Ill patients. Biomed Res Int generous donation to the Department of Anesthesiology of 2016; 2016:9781695 Göttingen, which made this work possible. 22. Bein T, Weber-Carstens S, Goldmann A, et al: Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2 removal ver- sus ‘conventional’ protective ventilation (6 ml/kg) in severe ARDS: REFERENCES The prospective randomized Xtravent-study. Intensive Care Med 1. 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29. Gattinoni L, Tonetti T, Quintel M: How best to set the ventilator on 31. Sharma AS, Weerwind PW, Bekers O, et al: Carbon dioxide dialysis in extracorporeal membrane lung oxygenation. Curr Opin Crit Care a swine model utilizing systemic and regional anticoagulation. Inten- 2017; 23:66–72 sive Care Med Exp 2016; 4:2 30. Schmidt M, Stewart C, Bailey M, et al: Mechanical ventilation man- 32. Atalan HK, Gucyetmez B, Dumantepe M, et al: The combined use agement during extracorporeal membrane oxygenation for acute of pumpless extracorporeal lung assist and continuous arteriovenous respiratory distress syndrome: A retrospective international multi- hemofiltration with citrate anticoagulation in polytrauma patients. center study. Crit Care Med 2015; 43:654–664 Intensive Care Med 2015; 41:2024–2025
8 www.ccmjournal.org XXX 2018 • Volume XX • Number XXX Copyright © 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. RESPIRATORY CARE Paper in Press. Published on July 01, 2014 as DOI: 10.4187/respcare.03184
The Successful Management of a Patient With Exacerbation of Non-Cystic Fibrosis Bronchiectasis and Bilateral Fibrothorax Using a Venovenous Extracorporeal Carbon Dioxide Removal System
Giovanna Arcaro MD and Andrea Vianello MD
Following unsuccessful treatment with noninvasive ventilation (NIV), patients requiring subsequent placement on invasive mechanical ventilation have a high mortality rate. Invasive mechanical ventilation is particularly problematic in patients with acute respiratory failure due to bronchiec- tasis exacerbation, as it is associated with a mortality rate of 19–35% and prolonged ICU stay. Here, we describe the successful management of a patient with exacerbated non-cystic fibrosis
bronchiectasis using a pump-assisted venovenous system for extracorporeal CO2 removal (ProLUNG system) as an alternative to endotracheal intubation following NIV failure. The extracorporeal CO2 removal system proved to be safe and efficacious in this case study, and further studies focusing on
its use in these types of cases seem warranted. Key words: bronchiectasis; extracorporeal CO2 re- moval; noninvasive ventilation. [Respir Care 2014;59(12):1–•. © 2014 Daedalus Enterprises]
Introduction NIV in bronchiectasis exacerbations may appear attractive as it can reduce ICU stay, its failure rate exceeds 25%.5 At Although the efficacy of noninvasive ventilation (NIV) the same time, subsequent application of invasive mechan- in reducing the need for endotracheal intubation and mor- ical ventilation, which is associated with a mortality rate of tality has been clearly established, its failure rate remains 19–35% and prolonged ICU stay, appears problematic.6 high, exceeding 20% in patients without COPD.1,2 A high According to the National Institute for Health and Care mortality rate has been recently reported in a large group Excellence guidance document issued in June 2012,7 ex- of patients who, following unsuccessful treatment with tracorporeal CO2 removal should be used to remove CO2 NIV, required subsequent application of invasive mechan- from the blood of patients receiving mechanical ventila- 2 ical ventilation. tion who are unable to achieve adequate gas exchange at Non-cystic fibrosis bronchiectasis is a progressive con- maximal tolerable ventilation pressures. Sporadic case re- dition generally associated with chronic bacterial infec- ports and short case series concerning the use of an extra- tions and characterized by irreversible destruction and di- corporeal CO removal system in patients who develop lation of the airways.3 The clinical course of individuals 2 severe acute hypercapnic respiratory failure of various eti- with non-cystic fibrosis bronchiectasis is variable, with a ologies but do not respond adequately to NIV have been significant proportion of patients developing transient ex- acerbation leading to severe acute respiratory failure (ARF) published in recent years. Extracorporeal CO2 removal and requiring ventilatory support.4 Although the use of has, in fact, been successfully employed, and intubation has been avoided in some cases of exacerbation of COPD,8-12 cystic fibrosis, pulmonary fibrosis, severe 8 13 The authors are affiliated with the Respiratory Intensive Care Unit, City asthma, and bronchiolitis obliterans. Hospital of Padova, Padova, Italy. Despite increasing interest in the use of extracorporeal CO removal systems in patients who develop refractory The authors have disclosed no conflicts of interest. 2 hypercapnic ARF, its utility in the event of exacerbations Correspondence: Andrea Vianello MD, Unita`Operativa Fisiopatologia in non-cystic fibrosis bronchiectasis has not been assessed. Respiratoria, Azienda Ospedaliera di Padova, Via Giustiniani 1, 35128 This report describes the management of a patient with Padova, Italy. E-mail: [email protected]. exacerbated bilateral bronchiectasis, fibrothorax, and hy- DOI: 10.4187/respcare.03184 percapnic respiratory failure who was successfully treated
RESPIRATORY CARE • DECEMBER 2014 VOL 59 NO 12 1 Copyright (C) 2014 Daedalus Enterprises ePub ahead of print papers have been peer-reviewed, accepted for publication, copy edited and proofread. However, this version may differ from the final published version in the online and print editions of RESPIRATORY CARE RESPIRATORY CARE Paper in Press. Published on July 01, 2014 as DOI: 10.4187/respcare.03184 NON-CF BRONCHIECTASIS AND VENOVENOUS EXTRACORPOREAL CO2 REMOVAL
by extracorporeal CO2 removal following ineffective NIV hemodynamic side effects, and the levels were raised by support. 1–2 cm H2O without exceeding 6–8 cm H2O (maximal Ϯ PEEP, 5.1 1.7 cm H2O). Supplemental oxygen was added Case Report to the ventilator circuit. The patient was connected to the ventilator by a full face mask; colloid dressings were placed A 36-y-old male patient was admitted to the respiratory on the major pressure points to minimize skin injury. NIV ICU of the City Hospital of Padova, Italy, for ARF. With was delivered continuously except for brief rest periods a known case of severe bilateral bronchiectasis, bullous (30–60 min) to allow the patient to receive dietary liquid emphysema, and bilateral fibrothorax diagnosed at the age supplements and to speak. A standard ICU monitoring of 27 y, the patient presented with a history of increasing system displaying electrocardiogram, pulse oximetry, in- productive cough and breathing difficulty over the preced- vasive blood pressure, and breathing frequency measure- ing week’s time, accompanied by orthopnea, hypersom- ments was utilized. nolence, asthenia, and palpitations. The patient also re- Despite continuous use of NIV, pulmonary gas exchange ported suffering from recurrent lower respiratory tract progressively deteriorated: on day 3 after admission, arte- infections over the preceding 3 y. Besides his regular ther- rial blood gas levels resulted in increasingly severe hyp- apy, he was receiving long-term oxygen therapy with noc- oxia and hypercapnia (pH 7.29, P of 89 mm Hg, and CO2 turnal NIV. Three months before admission to the hospi- P of 59 mm Hg during assist ventilation). The patient aO2 tal, the patient was placed on a waiting list for bilateral also showed signs of exhaustion (breathing frequency of lung transplantation with a normal priority status because 30–40 breaths/min), increasing intolerance to uninter- of increasing deterioration of ventilatory function, a vital rupted NIV, and an imminent need for invasive mechan- capacity of 25% predicted (1.33 L). ical ventilation. In view of the high risk of complications At admission, the patient was moderately agitated, tachy- linked to invasive ventilation, we informed the patient cardic, polypneic, and fatigued. Physical examination re- about an alternative venovenous extracorporeal CO2 re- vealed pulmonary cachexia and tachypnea (breathing fre- moval method available in our hospital that had already quency of 30 breaths/min), cyanosis, weak cough with been approved for an investigational feasibility study by purulent sputum, and diffuse subcrepitant bilateral rales. our local ethics committee. He was also provided detailed He was severely hypoxic and hypercapnic breathing room information about the benefits and risks of that system. air, and arterial blood gas values were pH 7.36, P of The extracorporeal CO removal device used in our aCO2 2 68 mm Hg, P of 50 mm Hg, and HCO Ϫ of 38.1 mmol/L. center is the ProLUNG system (Estor, Milan, Italy), a aO2 3 After supplemental oxygen was provided, CO2 retention pump-driven venovenous system that utilizes a small sin- further increased (pH 7.30, P of 89 mm Hg, P of gle venovenous dual-lumen catheter (13 French) that can aCO2 aO2 60 mm Hg, HCO Ϫ of 43.4 mmol/L, and P /F of 201). be inserted into a femoral or jugular vein. It is character- 3 aO2 IO2 Complete hematological workup revealed moderate ane- ized by a low blood flow (up to a maximum of 450 mL/min) mia (hemoglobin, 8.7 g/L) and leukocytosis (white blood and a single-use-only gas exchange cartridge consisting of cells, 13,600 ϫ 106 cells/L); serum electrolytes were nor- a hollow fiber polypropylene diffusion membrane network mal. A chest x-ray showed bilateral thick parallel lines in with an effective surface area of 1.35 m2. As the device the lower lobes, emphysematous bullae of the right and uses a total volume circuit of only 120 mL, the hemody- left upper lobes, bilateral pleural thickening, and a small namic impact on the patient is minimized. Oxygen flows calcification. The patient was treated with intravenous pip- as a carrier gas within the hollow fibers, and CO2 moves eracillin, levofloxacin, and diuretics. by selective diffusion across the concentration gradient As ventilatory assistance was needed, NIV was initiated from the blood. using a portable ventilator (Elise´e 150, ResMed San Di- The patient gave his consent to treatment with this de- ego, California) set on the pressure support ventilation vice. While the patient was supine, a 13 French catheter mode. Pressure support ventilation was initially titrated to was inserted percutaneously without complication via the a moderate tidal volume (6–8 mL/kg). The ventilatory right femoral vein and connected to the extracorporeal setting was then readjusted according to arterial blood circuit. Blood flow was initiated through the circuit by a gas values; our goals were to maintain arterial oxygen centrifugal pump at 300 mL/min. Oxygen flow through the saturation (S )atϾ 90%, P at Ͻ 50 mm Hg, and to gas exchanger was initiated at 12 L/min to maximize CO aO2 aCO2 2 reduce the breathing frequency. The initial pressure sup- removal. In accordance with study protocol guidelines for port level did not exceed 25 cm H2O and was progres- anticoagulation, the patient was started on an intravenous sively elevated by 1–2 cm H2O without exceeding heparin infusion to maintain an activated clotting time of 40 cm H2O due to the high risk of pneumothorax (maxi- 150–180 s). Ϯ mal pressure support, 25.8 2.6 cm H2O). PEEP was set The amount of CO2 removed by the device was adjusted at5cmH2O to obtain the best oxygenation with minimal depending on the arterial blood gas and breathing fre-
2RESPIRATORY CARE • DECEMBER 2014 VOL 59 NO 12 Copyright (C) 2014 Daedalus Enterprises ePub ahead of print papers have been peer-reviewed, accepted for publication, copy edited and proofread. However, this version may differ from the final published version in the online and print editions of RESPIRATORY CARE RESPIRATORY CARE Paper in Press. Published on July 01, 2014 as DOI: 10.4187/respcare.03184 NON-CF BRONCHIECTASIS AND VENOVENOUS EXTRACORPOREAL CO2 REMOVAL
poreal support was suspended. The catheter was removed, coagulation values were normal, and there was no addi- tional bleeding. The patient was subsequently supported with nighttime NIV. There were no other complications
during or after extracorporeal CO2 removal. On day 7, the patient was transferred to the pulmonary division in good clinical condition. He was mildly hypercapnic during sup- plemental oxygen therapy, and the arterial blood gas val- ues were pH 7.40, P 54.3 mm Hg, P 87 mm Hg, aCO2 aO2 HCO Ϫ 34 mmol/L, and P /F 310.7. He was subse- 3 aO2 IO2 quently discharged from the hospital on home nighttime ventilation via nasal mask.
Discussion
Some individuals with bronchiectasis require intensive care therapy and ventilatory support for ARF: in that event, noninvasive ventilatory management can become prob- lematic due to severe blood gas derangement, partially ineffective cough, and airway mucus encumbrance, which can lead to the need for endotracheal intubation. A sub- stantial proportion of patients with bronchiectasis fail to be weaned from invasive mechanical ventilation due to inad- equate cough, generalized weakness, and/or hemodynamic instability, which is possibly the outcome of cor pulmo- nale, and they should be considered at high risk for com- plications such as development of ventilator-associated pneumonia or ventilator-induced lung injury, severe sep- sis, and multi-organ failure syndrome.6,14 There are no studies to date concerning utilization of
extracorporeal CO2 removal devices as an alternative to endotracheal intubation to treat patients with bronchiecta-
Fig. 1. The subject on extracorporeal CO2 removal during a period sis exacerbation suffering from ARF in whom NIV treat- of rest from noninvasive ventilation. ment is ineffective. The findings from the case report out- lined here suggest that the timely use of an extracorporeal quency levels, which were measured every 4 h. During CO2 removal system in addition to NIV can prevent or application, the ProLUNG circuit blood flow varied from reduce the need for endotracheal intubation and avoid po- 300 to 450 mL/min; the remainder of gas exchange oc- tential problems linked to the application of invasive me- curred through the lungs using NIV adjusted to releasing chanical ventilation. The probability of weaning failure low tidal volume (6–8 mL/kg) with a low/moderate PEEP was particularly high in the patient described here due to level. coexisting fibrothorax, which may have impaired respira- P decreased after extracorporeal CO removal ther- tory mechanics and further increased the work of breath- aCO2 2 apy was initiated from 89 mm Hg before cannulation to ing.15 59 mm Hg within 24 h; the patient’s breathing frequency Although extracorporeal support devices present poten- also decreased from 30 to 16–18 breaths/min. P sub- tial complications, including vessel perforation, bleeding, aCO2 sequently remained within a range of 60–54 mm Hg for and infections,16 in our case, those drawbacks were min- the duration of therapy (Fig. 1). The patient’s clinical sta- imized by using venovenous cannulation as opposed to the tus progressively improved over the next 5 d, permitting a traditional veno-arterial cannulation and by reducing the reduction in NIV application from continuous use, except catheter size. Smaller catheters reduce circuit blood flows for brief rest periods, to 5–6 h off the ventilator by day 3. and hence the amount of CO2 removal. In the case studied, By day 4, the patient was able to breathe without ventila- the level of gas exchange was nevertheless satisfactory in tory support for 10 consecutive h. On day 5, the patient terms of improved arterial blood gas levels. Within 24 h, was increasingly active and clinically stable, and extracor- in fact, there was a relevant reduction in hypercapnia, with
RESPIRATORY CARE • DECEMBER 2014 VOL 59 NO 12 3 Copyright (C) 2014 Daedalus Enterprises ePub ahead of print papers have been peer-reviewed, accepted for publication, copy edited and proofread. However, this version may differ from the final published version in the online and print editions of RESPIRATORY CARE RESPIRATORY CARE Paper in Press. Published on July 01, 2014 as DOI: 10.4187/respcare.03184 NON-CF BRONCHIECTASIS AND VENOVENOUS EXTRACORPOREAL CO2 REMOVAL a 30 mm Hg fall in P , and the mean arterial pH reached guidance 428. Issued June 2012. http://guidance.nice.org.uk/ipg428. aCO2 ϳ7.40. Accessed on June 2, 2014. Finally, as the device did not require specialized staff/ 8. Kluge S, Braune SA, Engel M, Nierhaus A, Frings D, Ebelt H, et al. Avoiding invasive mechanical ventilation by extracorporeal carbon training and proved simple to use, it is presumable that it dioxide removal in patients failing noninvasive ventilation. Intensive could be safely implemented in any medical or surgical Care Med 2012;38(10):1632-1639. ICU. 9. Bonin F, Sommerwerck U, Lund LW, Teschler H. Avoidance of To summarize, the satisfactory outcome of this case intubation during acute exacerbation of chronic obstructive pulmo- confirms the importance of designing other studies to as- nary disease for a lung transplant candidate using extracorporeal carbon dioxide removal with the Hemolung. J Thorac Cardiovasc sess the use of venovenous extracorporeal CO2 removal systems in patients with exacerbated bronchiectasis and Surg 2013;145(5):e43-e44. 10. Lund LW, Federspiel WJ. Removing extra CO2 in COPD patients. severe respiratory failure in whom NIV alone is ineffec- Curr Respir Care Rep 2013;2:131-138. tive. 11. Mani RK, Schmidt W, Lund LW, Herth FJ. Respiratory dialysis for avoidance of intubation in acute exacerbation of COPD. ASAIO J REFERENCES 2013;59(6):675-678. 12. Burki NK, Mani RK, Herth FJ, Schmidt W, Teschler H, Bonin F, et 1. Hill NS, Brennan J, Garpestad E, Nava S. Noninvasive ventilation in al. A novel extracorporeal CO2 removal system: results of a pilot acute respiratory failure. Crit Care Med 2007;35(10):2402-2407. study of hypercapnic respiratory failure in patients with COPD. Chest 2. Walkey AJ, Wiener RS. Use of noninvasive ventilation in patients 2013;143(3):678-686. with acute respiratory failure, 2000-2009: a population-based study. 13. Moscatelli A, Ottonello G, Nahum L, Lampugnani E, Puncuh F, Ann Am Thorac Soc 2013;10(1):10-17. Simonini A, et al. Noninvasive ventilation and low-flow veno-ve- 3. O’Donnell AE. Bronchiectasis. Chest, 2008;134(4):815-823. nous extracorporeal carbon dioxide removal as a bridge to lung 4. Loebinger MR, Wells AU, Hansell DM, Chinyanganya N, Devaraj transplantation in a child with refractory hypercapnic respiratory A, Meister M, Wilson R. Mortality in bronchiectasis: a long-term study assessing the factors influencing survival. Eur Respir J 2009; failure due to bronchiolitis obliterans. Pediatr Crit Care Med 2010; 34(4):843-849. 11(1):e8-e12. 5. Dupont M, Gacouin A, Lena H, Lavoue´S, Brinchault G, Delaval P, 14. Alzeer AH, Masood M, Basha SJ, Shaik SA. Survival of bronchi- Thomas R. Survival of patients with bronchiectasis after the first ectatic patients with respiratory failure in ICU. BMC Pulm Med ICU stay for respiratory failure. Chest 2004;125(5):1815-1820. 2007;7:17. 6. Phua J, Ang YL, See KC, Mukhopadhyay A, Santiago EA, Dela 15. Criner GJ, Brennan K, Travaline JM, Kreimer D. Efficacy and com- Pena EG, Lim TK. Noninvasive and invasive ventilation in acute pliance with noninvasive positive pressure ventilation in patients respiratory failure associated with bronchiectasis. Intensive Care Med with chronic respiratory failure. Chest 1999;116(3):667-675. 2010;36(4):638-647. 16. Bein T, Weber F, Philipp A, Prasser C, Pfeifer M, Schmid FX, et al. 7. National Institute for Health and Care Excellence. Extracorporeal A new pumpless extracorporeal interventional lung assist in critical membrane carbon dioxide removal. NICE interventional procedure hypoxemia/hypercapnia. Crit Care Med 2006;34(5):1372-1377.
4RESPIRATORY CARE • DECEMBER 2014 VOL 59 NO 12 Copyright (C) 2014 Daedalus Enterprises ePub ahead of print papers have been peer-reviewed, accepted for publication, copy edited and proofread. However, this version may differ from the final published version in the online and print editions of RESPIRATORY CARE Morelli et al. Intensive Care Medicine Experimental 2015, 3(Suppl 1):A824 http://www.icm-experimental.com/content/3/S1/A824
POSTERPRESENTATION Open Access Extracorporeal co2 removal in hypercapnic patients who fail noninvasive ventilation and refuse endotracheal intubation: a case series A Morelli*,AD’Egidio, A Orecchioni, F Alessandri, L Mascia, VM Ranieri From ESICM LIVES 2015 Berlin, Germany. 3-7 October 2015
Introduction differ between the two study groups. At the baseline, 20 Noninvasive ventilation (NIV) represents the standard of patients in the treated group and 16 in the control care for patients with exacerbation of chronic obstruc- group required norepinephrine to maintain mean arter- tive pulmonary disease. However, NIV fails in almost ial pressure, at the doses of 0.46 ± 0.18 and 0.37 ± 0.15 40% of the most severe forms of acute hypercapnic (mean ± SD) µg/Kg/min respectively, without statisti- respiratory failure and patients must undergo endotra- cally significant differences.A significant reduction of cheal intubation and invasive ventilation. Such transition PaCo2 from baseline to 96 hours of treatment was from NIV to invasive ventilation is associated to observed in both group (p < 0.05) and reached between increased mortality. Under these circumstances, patients groups difference only at 24 hours. An increase in arter- may express a clear intention not to be intubated. ial pH were observed from baseline to 96 hours of treat- ment in both groups (p < 0.05) and between groups Objectives difference was observed at 96 hours (p < 0.004, Fig 1 To assess efficacy and safety of noninvasive ventilation- and 2). The duration of extracorporeal Co2 removal was plus-extracorporeal Co2 removal in patients who fail 4.8 ± 3 (mean ± SD) days. The longer duration of treat- NIV and refuse endotracheal intubation. ment was 16 days. At day 14, the percentage of patients requiring norepinephrine was lower in the treated group Methods compared to the control group, 30 % vs. 60 % respectively We reported data from a case series of 30 patients with (p = 0.04). Mortality at day 28 was significantly lower in acute hypercapnic respiratory failure due to exacerbation the treated group than in control group (23.3 % vs. 58.1 %, of chronic obstructive pulmonary disease, who refused p < 0.001, Fig 3). In the treated group none of patients endotracheal intubation after failing NIV and therefore experienced bleeding events with a heparin infusion in the were treated with extracorporeal Co2 removal plus NIV circuit of 5.6 ± 1.5 (mean ± SD) UI/Kg/h. Nevertheless as last resort therapy. All patients acknowledged the 8 patients had clots in the circuit which required the sub- nature of last resort therapy and gave consent to treat- stitution of the circuit. ment. Collected data of these patients were then retro- spectively matched with data obtained from 30 historical Conclusions controls who received conventional treatment with Our results support the need for a large randomized endotracheal intubation. controlled clinical trial to test the hypothesis that extra- corporeal Co2 removal may contribute to improve survi- Results val in patients with acute hypercapnic respiratory failure After matching the patients, demographic characteristics due to exacerbation of chronic obstructive pulmonary including age, BMI, gender and SOFA II score did not disease.
Policlinico Umberto I° University of Rome La Sapienza, Anesthesiology and Intensive Care, Rome, Italy
© 2015 Morelli et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Morelli et al. Intensive Care Medicine Experimental 2015, 3(Suppl 1):A824 Page 2 of 2 http://www.icm-experimental.com/content/3/S1/A824
Published: 1 October 2015
doi:10.1186/2197-425X-3-S1-A824 Cite this article as: Morelli et al.: Extracorporeal co2 removal in hypercapnic patients who fail noninvasive ventilation and refuse endotracheal intubation: a case series. Intensive Care Medicine Experimental 2015 3(Suppl 1):A824.
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Figure 3 Submit your next manuscript at 7 springeropen.com LFVVECCO2-R IN COPD EXACERBATIONS: EXPERIENCE IN TWO PATIENTS Pastore A, Pagnucci N, Colonna R, Giunta M, Mori R, Forfori F. AOUP, Anestesia e Rianimazione IV, Stabilimento di Cisanello Direttore: Prof. Francesco Giunta INTRODUZIONE: la NIV è attualmente considerata il trattamento di scelta nell’ insufficienza respiratoria legata alle riacutizzazioni di BPCO. Essa migliora gli scambi respiratori e il pH arterioso; in alcuni pazienti, però, la NIV fallisce, per cui si deve ricorrere alla intubazione. OBIETTIVI: nella nostra esperienza, abbiamo unito la NIV al supporto extra-corporeo di rimozione della CO2, con sistema veno- venoso a bassi flussi (LFVVECCO2-R, ProLUNG, ESTOR Spa), allo scopo di superare la fase acuta di malattia ed evitare il ricorso alla VM invasiva. DESCRIZIONE: PAZIENTE T.U. (n.1) 120 120 200 100 100 150 80 80
60 60 PaO2 100 mmHg 40 40 PaCO2 50 20 20 0 0 0 admitt. after 48 hrs T1 T6 CPAP + T6 T12 T24 T48 LFVVECCO2-R Patient n.1 Before After treatment treatment PAZIENTE M.G. (n.2) pH 7.18 7.35 120 pO2 102.2 89.8 100 pCO2 67 39.4
80 60 mmHg 40 Patient n.2 Before After 20 treatment treatment 0 pH 7.25 7.32 T0 T3 T6 T24 ProLUNG – Estor Spa pO2 60.7 60.1 pCO2 89.3 73
DISCUSSIONE: in entrambi i casi, l’ associazione tra NIV e
LFVVECCO2-R ha garantito adeguati scambi respiratori e una gestione ottimale della fase acuta. Quando, nel paziente n.1, la IOT si è resa necessaria, il sistema LFVVECCO2-R ha consentito una ventilazione ultra-protettiva.
CONCLUSIONI: LFVVECCO2-R può rappresentare un prezioso strumento nel management delle riacutizzazioni di BPCO, con miglioramento dell’ outcome e maggiore comfort per il paziente. CE: Swati; MCC220105; Total nos of Pages: 8; MCC220105
REVIEW
CURRENT OPINION Management of acute hypercapnic respiratory failure
Lara Pisani, Nadia Corcione, and Stefano Nava
Purpose of review The objective of this article is to review the most recent literature regarding the management of acute hypercapnic respiratory failure (AHRF). Recent findings In the field of AHRF management, noninvasive ventilation (NIV) has become the standard method of providing primary mechanical ventilator support. Recently, extracorporeal carbon dioxide removal (ECCO2R) devices have been proposed as new therapeutic option. Summary NIV is an effective strategy in specific settings and in selected population with AHRF. To date, evidence on ECCO2R is based only on case reports and case-control trials. Although the preliminary results using ECCO2R to decrease the rate of NIV failure and to wean hypercapnic patients from invasive ventilation are remarkable; further randomized studies are needed to assess the effects of this technique on both short-term and long-term clinical outcomes. Keywords chronic obstructive pulmonary disease, extracorporeal carbon dioxide removal, hypercapnia, noninvasive ventilation
INTRODUCTION acute respiratory failure. The determination of a Acute hypercapnic respiratory failure (AHRF) PaCO2 > 45 mmHg is diagnostic of hypercapnia. remains a common medical emergency. Hypercapnic respiratory failure is more com- In this review, we discuss the physiological monly determined by the reduction of alveolar mechanisms responsible for AHRF and the chal- ventilation (pump respiratory failure), than by the lenges involved in its management. We critically increase of the rate of CO2 production, even in high- examine the current literature focusing on the effi- risk patients with poor pulmonary reserve. A cacy of noninvasive ventilation (NIV) in specific reduction in effective alveolar ventilation may result settings. The recent findings regarding the possible either from a rise in the dead space or from a role of new generation extracorporeal carbon diox- reduction of minute ventilation. ide removal (ECCO2R) devices in patients with A rapid elevation of PaCO2 leads to a drop hypercapnia are also included. of arterial blood pH as a consequence of the À HCO3 /PaCO2 ratio’s lowering. Respiratory acidosis (pH < 7.35 and concomitant hypercapnia) is the ACUTE HYPERCAPNIC RESPIRATORY characteristic landmark of acute decompensated FAILURE
Pathophysiology and causes Department of Clinical, Integrated and Experimental Medicine (DIMES), Respiratory and Critical Care Unit, Sant’Orsola Malpighi Hospital, Alma The normal level of carbon dioxide (CO2) tension in Mater University, Bologna, Italy the arterial blood (PaCO2) results from the relation- Correspondence to Stefano Nava, Department of Clinical, Integrated and ship between the rate of CO2 production and the Experimental Medicine (DIMES), Respiratory and Critical Care, portion of CO2 eliminated by the lung with alveolar Sant’Orsola Malpighi Hospital, Via Massarenti n.9, 40138 Bologna, Italy. ventilation [1]. E-mail: [email protected] Thearterialbloodgasanalysisisthegold Curr Opin Crit Care 2016, 22:000–000 standard for assessing PaCO2 in patients with DOI:10.1097/MCC.0000000000000269
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Respiratory system
Special reference also needs to be made to the KEY POINTS role of high-flow nasal cannulae (HFNC) in patients AHRF is considered an emergency situation and its with hypercapnia. HFNC is a device able to deliver management has changed during the past decades. heated and humidified oxygen at high flows (up to 60 l/min) [6&]. Thanks to higher flow, the system is The role and the efficacy of NIV in specific situations able to match or exceed the patient’s spontaneous that cause AHRF are well established and NIV is inspiratory flow rate, thus attenuating inspiratory actually the first-line treatment in selected population. resistance within the nasopharynx. Additional Recently, ECCO2R devices have been suggested as a potential benefits of HFNC include the washout of new treatment option either in avoiding intubation in upper airway dead space that seems to minimize COPD patients at risk of NIV failure and in facilitating rebreathing of CO2. Finally, HFNC generates a low- weaning in mechanically ventilated level positive airway pressure (PEEP effect) that hypercapnic patients. varies according to the flow setting and the breath- ing [6&]. For all those reasons, HFNC has been pro- posed to reduce the work of breathing and respiratory rates, countering intrinsic PEEP, especi- ventilatory failure and it is considered an emergency ally in COPD patients [7–9]. situation. Although HFNC is considered the latest trend in the management of various conditions such as hypoxemic respiratory failure [10&,11&,12&&], further Principles of management studies are needed to determine if a real advantage of When a patient develops shortness of breath, a using HFNC in the acute decompensated ventilatory change in mental status, such as hypersomnolence, failure exists. or oxygen desaturation, the presence of hypercapnia should always be suspected and checked, especially if the patient is at risk for hypoventilation (i.e., use NONINVASIVE MECHANICAL of sedatives), or the patient is affected by chronic VENTILATION IN THE TREATMENT OF lung diseases that increase physiologic dead space ACUTE HYPERCAPNIC RESPIRATORY [i.e., chronic obstructive pulmonary disease (COPD) FAILURE exacerbation]. The role and the efficacy of NIV in specific situations Once the diagnosis of acute hypercapnia is that cause AHRF are well established. NIV has made, the clinician should stabilize the patient by changed radically the treatment of AHRF shifting performing a rapid clinical bedside assessment and its management from invasive mechanical venti- administering the standard medical therapy. As lation (IMV) to noninvasive strategy, consequently, soon as possible, the clinician should collect the decreasing the morbidity and mortality associated medical history, perform a more accurate physical with the intubation and IMV. examination, and other tests like a chest radiograph to determine and treat the specific underlying causes and precipitant factors of AHRF. Physiological effects of noninvasive ventilation Both invasive and noninvasive ventilation are able Oxygen therapy to increase alveolar ventilation and reduce the work Healthcare providers should pay careful attention of breathing, assisting spontaneous respiratory administering the oxygen therapy in patients with muscle activity. Consequently, in patients with COPD or other known risk factors that can predis- acute respiratory failure, NIV significantly reduces pose to hypercapnic respiratory failure with acidosis PaCO2 and improves respiratory acidosis. NIV pro- [2,3]. For this subgroup of patients, a target satur- duces a significant increase in tidal volume that is ation range of 88–92% is recommended to avoid associated to an improvement of the breathing pat- hypoxemia and reduce the risk of oxygen-induced tern, in particular to a reduction in respiratory hypercapnia [2–4]. Therefore, oxygen saturation rate [13,14]. should be monitored continuously and the patient’s Several studies have shown that NIV with appro- further treatment should be guided by the results of priate levels of inspiratory positive pressure reduces the arterial blood gas analysis [3]. In fact, if respir- WOB, as demonstrated by a marked reduction in atory acidosis persists despite appropriate medical both esophageal pressure and transdiaphragmatic treatment it is mandatory to consider mechanical pressure [14]. Additionally, inspiratory positive pres- ventilation [5]. sure causes a reduction in the mean pressure–time
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Management of acute hypercapnic respiratory failure Pisani et al.
product of the inspiratory muscles [13,15], an index invasive ventilation. In particular, NIV was associ- of the muscle oxygen consumption. NIV is able to ated with lower risk of mortality [odds ratio 0.54; reduce elastic WOB also by using PEEP that supplies (95% CI, 0.48–0.61)] and a lower risk of hospital- all or part of the driving pressure required to over- acquired pneumonia [(odds ratio, 0.53 (95% CI, come intrinsic PEEP, especially in COPD patients. 0.44–0.64)] [30&]. Moreover, applying positive pressure to the respiratory system ameliorates the gas exchange Acute pulmonary edema by increasing functional residual capacity, facilitat- Acute pulmonary edema (APE) is characterized by ing the distensibility of lung parenchyma, recruit- the rapid increase in the pulmonary capillary wedge ing areas of atelectasis/dystelectasis, and producing pressure that leads to interstitial and alveolar edema. a higher alveolar pressure that contrasts fluid Consequently, the lung compliance decreases and extravasation from the vascular bed. This may the WOB increases [31]. Therefore, patients with improve ventilation/perfusion (Va/Q) mismatch- APE present an acute onset of symptoms and a rapid ing and allows a more uniform distribution of venti- worsening of the clinical status, characterized by lation. severe respiratory distress that requires direct admis- On the other hand, it is important to consider sion to the emergency department. In addition, also potential adverse effects on cardiovascular func- around 50% of patients with severe APE are hyper- tion when administering NIV. It is known that, in capnic when admitted to the hospital and hyper- normal volunteers, the overall effect of a continuous capnia is a strong predictor of immediate airway positive airway pressure (CPAP) of 15 cm H2O, deliv- intubation [32]. As demonstrated by a recent pro- ered by a nasal mask, is to ‘decrease cardiac output’ spective study [33&], patients with hypercapnia were by 20%–30% [13,16]. Approximately the same more likely to be in severe functional class [New reduction has been demonstrated in stable COPD York Heart Association (NYHA) class IV], to have [17] and in patients with decompensated COPD [18] abrupt onset and to present with an usual ‘radio- as well. logic’ appearance of APE compared with hyponor- mocapnic patients. Another observational study [34&], after excluding patients with associated The magnificent four: any news? underlying chronic lung diseases, showed that Taking into account particular patients with AHRF, patients with severe hypercapnia at admission NIV is considered the gold standard in four (PaCO2 > 60 mmHg) needed longer time on NIV different settings. (>48 h) than nonhypercapnic patients; no signifi- cant difference has been shown between the two groups regarding the intubation rate. Exacerbation of chronic obstructive NIV support delivered by either CPAP and pres- pulmonary disease sure support ventilation have shown the same The most clear evidence on the efficacy of NIV is results also in terms of efficacy in patients with demonstrated in COPD population. Several con- APE, rapidly improving patients’ symptoms and trolled randomized studies have shown that NIV, gas exchange, and reducing the need of invasive added to standard medical treatment, is effective in mechanical ventilation compared with standard reducing mortality, avoiding intubation, reducing medical therapy alone [35–37]. The two ventilation the risk of developing pneumonia, improving dysp- modalities have similar benefits also in the subgroup noea, reducing hospital length of stay, and reducing of patients affected by APE associated with hyper- costs in COPD patients with acute respiratory fail- capnia [38]. However, CPAP is considered cheaper ure, when compared with medical management and easier than NIV as it requires limited equipment plus oxygen therapy alone [19–23]. Meta-analyses and minimal staff training and it is often used as first of randomized controlled trials suggested that NIV treatment choice in the emergency department or in canreducetheriskofdeathbyupto55%,revealing a prehospital setting. itself as the only hospital-based intervention known to improve mortality [24–26,27&]. This benefit probably results from the prevention of Weaning from invasive ventilation in complications associated with IMV, including chronic obstructive pulmonary disease ventilator-associated pneumonia [28,29]. A recent Invasive ventilation provides effective and life-saving large retrospective study [30&]ofmorethan25000 support for patients with acute respiratory failure. It is patients confirmed that patients hospitalized for indicated when NIV is not recommended or when COPD exacerbation and initially treated with NIV NIV has failed. Because an endotracheal tube is used had better outcomes than those that received as an artificial airway, the cough reflex is suppressed,
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increasing the risk of ventilator associated pneumo- Therefore, the early use of NIV is now recom- nia, which correlates with both increased morbidity mended in the prevention of postextubation failure and mortality [39–41]. Other clinical complications in selected patients with chronic respiratory disease, related to a prolonged intubation include respiratory cardiac comorbidity, and in those with hypercapnic muscle weakness, upper airway disorder, and sinu- respiratory failure during a spontaneous breathing sitis. In general, the risk for adverse events rises with trial. In contrast, no clear evidence of benefit has the duration of intubation [42]. been demonstrated in mixed populations who have To reduce these complications, the role of NIV already developed postextubation respiratory failure in weaning strategy has been investigated. [60&]. Historically, the first study [43] that used NIV in the weaning process was performed in 50 severe COPD patients admitted for an exacerbation. WHEN NONINVASIVE VENTILATION Within 48 h after mechanical ventilation was FAILS? THE ROLE OF EXTRACORPOREAL initiated, patients who failed the T-piece trial were CARBON DIOXIDE REMOVAL randomized to either extubation and supported Despite the positive results and the increasing with noninvasive pressure support ventilation or experience with this technique, NIV failure occurs to continue conventional weaning with the endo- in 25–50% of patients with COPD exacerbation tracheal tube. The group of patients who were extu- [61–63]. Additionally, COPD patients who require bated and received NIV remained ventilated for IMV have poor prognosis and an increased risk significantly shorter periods, and had a lower inci- of difficult weaning and prolonged ventilation dence of nosocomial pneumonia as well as a higher [64–66]. 60 days survival rate compared with the control In recent years, new generation ECCO2R devices group. have been proposed in addition to NIV to reduce the After this first experience, several randomized rate of endotracheal intubation in COPD patients, controlled studies were published [44–50]. Taken suggesting ECCO2R as new therapeutic option. together, the randomized controlled trials indicated ECCO2R technology is based on a modified con- that using NIV to facilitate weaning is not inferior to tinuous venovenous hemofiltration circuit. The invasive weaning in particular in very selected devices are equipped with a membrane lung that patients such as those with COPD exacerbation allows the elimination of CO2 from the blood. where noninvasive support has the same physiologi- Compared with conventional extracorporeal mem- cal effects and results obtained when NIV is applied brane oxygenation, ECCO2R presents many advan- as primary treatment in COPD. tages including a lower blood flow rate (range from In fact, a recent meta-analysis [51&] on this topic 300 up 1500 ml/min) and consequently smaller concluded that NIV reduces mortality, ventilator- venovenous catheters (12–14 French). Continuous associated pneumonia, the length of stay in the ICU infusion of heparin is also needed to ‘prevent clot- or hospital, without increasing the risk of weaning ting’ of the circuit. failure or reintubation. Originally, ECCO2R has been suggested in acute Therefore, in accordance with the recent eviden- respiratory distress syndrome to manage permissive ces, NIV is recommended to reduce the duration of hypercapnia, allowing very small tidal volume invasive ventilation facilitating weaning preferen- [67&]. tially in patients with COPD and in a highly moni- Actually, no randomized clinical trials on tored setting. ECCO2R in the COPD population were published. A recent systematic review [68&] identified 10 studies (87 patients) about this topic. It included Prevention of postextubation respiratory primarily case series and case reports [69–76] and failure in high-risk patients only two case-control studies in which patients Postextubation respiratory failure occurs in a per- treated with ECCO2R were matched to historical centage of patients varying from 2 to 20% [52], controls [77&&,78]. In addition, Table 1 shows usually within 48–72 h after extubation [53,54]. the currently ongoing studies regarding the use Several studies have demonstrated that in patients of ECCO2R in hypercapnic respiratory failure considered at risk, the early application of NIV can patients [79–83]. reduce the incidence of postextubation respiratory Results derived from this review demonstrated failure, the need for reintubation, and the overall [68&] that ECCO2R avoided intubation in 65/70 mortality with a varying degree of success according (93%) patients. Moreover, 9/17 (53%) patients were to the nature and severity of the underlying disease weaned successfully from invasive ventilation by [55–59]. using ECCO2R. However, many complications have
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ClinicalTrials.gov Hypothesis/primary Inclusion Estimated Recruitment Identifier/Official Title Study design outcome criteria enrollment Device status
Prevention of intubation in COPD exacerbation NCT02086084 Randomized, The hypothesis is that the addition Known COPD with an acute 24 patients Hemolung RAS Recruiting ß Extra-corporeal CO2 controlled trial of ECCO2R to NIV will shorten exacerbation 06WlesKue elh n.Alrgt reserved. rights All Inc. Health, Kluwer Wolters 2016 Removal as an Adjunct the duration of NIV and reduce Patients with a persistent to Non-Invasive likelihood of intubation arterial pH < 7.30 due Ventilation in Acute Primary outcome: time to primarily to hypercapnic Severe Exacerbations cessation NIV respiratory failure after of COPD [79] standard medical therapy and at least 1 h of NIV NCT01784367 Prospective cohort Rate of intubation for invasive Acute or acute-on-chronic 30 patients ECLA Novalung Completed Extracorporeal Lung study mechanical ventilation hypercapnic respiratory Germany Assist to Avoid insufficiency (pH 7.35, Intubation in Patients PaCO2 > 45 mmHg) Failing Noninvasive Failure of noninvasive MCC220105 Ventilation for Acute ventilation Hypercapnic Fulfilling criteria for Respiratory Failure [80] endotracheal intubation
Stable COPD patients with chronic hypercapnic failure failure respiratory hypercapnic acute of Management
NCT02260583 Pilot study The aim of this study is to assess COPD Stable PaCO2 > 55 mmHg 15 patients Decap Smart, Hemodec Recruiting Effect of Extracorporeal the feasibility and safety of one nonrespondent to long-term NIV (Salerno, Italy) CO2 Removal in stable shot ECCO2R device, in (at least 1 week). This means a COPD patients with reducing the PaCO2 level decrease in PaCO2 during Chronic Hypercapnic Primary outcome: arterial blood spontaneous breathing, at least respiratory failure: a gases 4 h after the termination of NIV, pilot study [81] of<6% pH > 7.35 Clinical stability Facilitating extubation NCT02107222 Multicenter, To evaluate the clinical effect of Known history of COPD 120 patients PALP Not yet recruiting Multicenter randomized, PALP in reducing the time on experiencing an exacerbation
www.co-criticalcare.com Randomized Control controlled trial invasive ventilation in patients P/F ratio >150 mmHg Trial (RCT) to with an exacerbation of COPD Currently, endotracheally Determine Safety and requiring invasive mechanical intubated and requiring Efficacy of PALPTM for ventilation. invasive mechanical ventilation ECCO2-R in (must have been on invasive Conjunction With mechanical ventilation for Liberation From 24–48 h) Able to tolerate large Mechanical Ventilation bore i.v. cannulation required (MV) Compared to MV for proper operation of study Alone in COPD device Pisani Exacerbation and
Respiratory Failure [82] al. et 5
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been described with ECCO2R systems. In particular, , 2 adverse events including both major (significant bleeding, vein perforation, pneumothorax, and death) and minor complications (minor bleed, thrombocytopenia, circuit clotting, deep venous Recruitment status Recruiting thrombosis, pump malfunction, etc.) were observed in almost half of the patients [68&]. Finally, this meta-analysis does not include the preliminary data related to the effects of ECCO2R on lung mechanics [84&&]. As shown in Table 1, our team is conducting a pilot study about the role of ECCO2R in COPD patients who failed spontaneous Pero (MI), Italy] breathing trials [83]. We demonstrated for the first time that the addition of ECCO2R during unsup- ported breathing is able to decrease the inspiratory muscle effort, reducing significantly the Pdi swing, the pressure–time products of the transdiaphrag- Estimated enrollment Device 12 patients ProLUNG [Estor S.p.A. matic pressure, and respiratory rate. Moreover, real carbon dioxide removal; NIV, noninvasive ventilation; PaCO ECCO2R prevents the increase of rapid shallow breathing index (f/VT) and PaCO2 during a T-piece trial, thereby avoiding respiratory acidosis and accelerating the weaning process in those patients. The study elucidated the physiologic effects of extracorporeal CO2 devices, providing the rationale for the application of ECCO2R in patients with 45 mmHg) during
> AHRF for the first time. 2 readiness to be weaned At least 2 unsuccessfulweaning T-piece trials, excluding the one of the experimentalPersistence trial of hypercapnia (PaCO invasive mechanical ventilation CONCLUSION Inclusion criteria Patients meeting the criteria for The approach to AHRF has changed during the last decades. According to better outcomes and lower mortality rates, NIV has shifted the AHRF manage- ment from invasive strategy to noninvasive one. As reviewed in this paper, the evidence about the use of NIV in specific settings and in selected population is strong. The main challenge we face today is to utilize a different way to eliminate the CO2 by the extrac- orporeal removal in addition to the ‘conventional approach’ consisting in the improvement of alveo- reintubation after removal of ECCO2R
Hypothesis/primary outcome lar ventilation by using a mechanical ventilator working together with the respiratory pump. However, further randomized studies are needed to better understand the role of ECCO2R both in the prevention of intubation and in facilitating weaning in mechanically ventilated hypercapnic respiratory failure patients. Pilot study Weaning success avoiding Acknowledgements ) None.
Financial support and sponsorship Continued ( None.
Conflicts of interest A Pilot Study onUse the of Extracorporeal CO2 Removal During the Weaning Process From Mechanical Ventilation [83] Table 1 ClinicalTrials.gov Identifier/Official TitleNCT02259335 Study design AHRF, acute hypercapnic respiratory failure; COPD, chronic obstructive pulmonary disease; ECLA, extracorporeal lung assist; ECCO2R, extracorpo carbon dioxide tension; PALP, Pump Assisted Lung Protection; RAS, Remote Access Service. There are no conflicts of interests.
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Noninvasive ventilation after extubation 77. Del Sorbo L, Pisani L, Filippini C, et al. Extracorporeal CO2 removal in in hypercapnica patients with chronic respiratory disorders: randomized && hypercapnic patients at risk of noninvasive ventilation failure: a matched controlled trial. Lancet 2009; 374:1082–1088. cohort study with historical control. Crit Care Med 2014; 43:120–127. 58. El-Solh AA, Aquilina A, Pineda L, et al. Noninvasive ventilation for prevention The study demonstrated the efficacy of ECCO2R in association to NIV to reduce of postextubation respiratory failure in obese patients. Eur Respir J 2006; need of endotracheal intubation in hypercapnic patients at risk of NIV failure 28:588–595. compared to a matched control group with similar patients treated with NIV only. 59. Girault C, Bubenheim M, Abroug F, et al. Noninvasive ventilation and weaning 78. Kluge S, Braune SA, Engel M, et al. Avoiding invasive mechanical ventilation in chronic hypercapnic respiratory failure patients: a randomized multicenter by extracorporeal carbon dioxide removal in patients failing noninvasive trial. Am J Respir Crit Care Med 2011; 184:672–679. ventilation. Intensive Care Med 2012; 38:1632–1639. 60. Bajaj A, Rathor P, Sehgal V, et al. Efficacy of noninvasive ventilation after 79. Barrett N, Camporota L, Hart N. ECCO2R as an adjunct to NIV in AECOPD. & planned extubation: a systematic review and meta-analysis of randomized 2014. http://ClinicalTrials.gov. NCT02086084. [Accessed September 2, controlled trials. Heart Lung 2015; 44:150–157. 2015] The meta-analysis confirms that the use of NIV immediately after planned extuba- 80. Kluge S. Extracorporeal lung assist to avoid intubation in patients failing tion decreases reintubation rate and is associated with better outcomes. noninvasive ventilation for acute hypercapnic respiratory Failure (ECLAIR). 61. Squadrone E, Frigerio P, Fogliati C, et al. Noninvasive vs invasive ventilation in 2013. http://ClinicalTrials.gov. NCT01784367. [Accessed September 2, COPD patients with severe acute respiratory failure deemed to require 2015] ventilatory assistance. Intensive Care Med 2004; 30:1303–1310. 81. Nava S. Effect of extracorporeal CO2 removal in stable hypercapnic COPD 62. Conti G, Antonelli M, Navalesi P, et al. Noninvasive vs. conventional mechan- patients. 2014. http://ClinicalTrials.gov. NCT02260583. [Accessed Septem- ical ventilation in patients with chronic obstructive pulmonary disease after ber 2, 2015] failure of medical treatment in the ward: a randomized trial. Intensive Care Med 82. Ranieri VM. The PALPTM-COPD trial (Low-flow CO2-removal (ECCO2-R) 2002; 28:1701–1707. in exacerbated COPD) (PALP-COPD). 2014. http://ClinicalTrials.gov. 63. Confalonieri M, Garuti G, Cattaruzza MS, et al. Italian noninvasive positive NCT02107222. [Accessed September 3, 2015] pressure ventilation (NPPV) study group: a chart of failure risk for noninvasive 83. Nava S. Weaning form mechanical ventilation using extracorporeal CO2 ventilation in patients with COPD exacerbation. Eur Respir J 2005; 25:348– removal (WeanPRO). 2014. http://ClinicalTrials.gov. NCT02259335. [Ac- 355. cessed September 1, 2015] 64. Menzies R, Gibbons W, Goldberg P. Determinants of weaning and survival 84. Pisani L, Fasano L, Corcione N, et al. Effects of extracorporeal CO2 removal among patients with COPD who require mechanical ventilation for acute && on inspiratory effort and respiratory pattern in patients that fail weaning from respiratory failure. Chest 1989; 95:398–405. mechanical ventilation. Am J Respir Crit Care Med (in press). 65. Scho¨ nhofer B, Euteneuer S, Nava S, et al. Survival of mechanically ventilated Preliminary data from this pilot study clarifies for the first time the physiologic patients admitted to a specialised weaning centre. Intensive Care Med 2002; effects of extracorporeal CO2 devices in patients that fail weaning from mechanical 28:908–916. ventilation.
8 www.co-criticalcare.com Volume 22 Number 00 Month 2016 Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Obiettivo
I pazienti con BPCO vanno incontro a grave insufficienza respiratoria ipercapnica che può evolvere in ipertensione polmonare e determinare ipertrofia del ventricolo destro con insufficienza cardiaca destra, cuore polmonare. Il ricorso alla ventilazione meccanica protettiva può complicare la gestione di questi pazienti. La rimozione extracorporea di CO2 è una soluzione attuabile al letto del paziente in grado di ristabilire l’omeostasi acido-base e di migliorare l’attività cardiaca (1,2). Abbiamo studiato la capacità di un dispositivo di rimozione extracorporea veno-venosa della CO2 per ridurre la ventilazione minuto, mantenendo Risultati normocarbia e stabilità emodinamica (3). L’utilità della metodica è risultata costante per tutta la durata della procedura. Non sono stati Metodi evidenziati effetti secondari o complicanze relative alla metodica in sé o all’impiego della In 20 pazienti in ventilazione meccanica a circolazione extracorporea. pressione controllata intubati da 48 ore è stato La ventilazione minuto è stata ridotta da 5,8 ± inserito un catetere a doppio lume 15 F in vena 1,7 L/min a 3 ± 1,1 L/min dopo 2 ore di
femorale e collegato al ProLUNG™ (Estor), trattamento. La rimozione della CO2 è stata di nuovo dispositivo extracorporeo a basso flusso 71 ± 1.2 mL/min a flussi ematici di 418 ± 6
per la rimozione di CO2. mL/min. La produzione di CO2 da parte del La ventilazione minuto è stata ridotta per polmone è diminuita del 50% ed è rimasto a
mantenere la normocarbia (PaCO2 35-45 quel livello successivamente (p<0,001). mmHg). Sono state registrate 2 ore dall’inizio del L'impatto emodinamico è stato trascurabile. trattamento e ogni 12 ore: parametri respiratori Il tempo di passaggio alla ventilazione non e modifiche del monitoraggio emodinamico non invasiva è stato in media di 22 ± 5 ore di invasivo (4). Con i controlli emogasanalitici sono trattamento.
stati quantificati la rimozione di CO2 da ProLUNG™ (mL/min), l’efficacia della membrana e gli effetti sul paziente. Raggiunta la Conclusioni normocarbia ed il miglioramento dei parametri emodinamici si passava alla ventilazione non La rimozione venovenosa di CO2 è un efficace invasiva (NIV). Il trattamento veniva continuato supporto della strategia di ventilazione per una durata non inferiore a 72 ore. protettiva permettendo un sicuro e veloce passaggio alla ventilazione non invasiva in pazienti con BPCO e grave compromissione Bibliografia cardiaca. ProLUNG™ garantisce la correzione dell’acidosi 1. Mielck F. and Quintel M. Cur Opin Crit Care 2005; 11:87-93. respiratoria e la stabilità emodinamica in 2. Livigni S. et al. Critical Care 2006, 10:R151 modo costante, con un limitato impegno di 3. Morris AH, Wallace CJ, Menlove RL, et al. Am J Respir Crit risorse, rendendo così possibile il suo impiego, Care Med 1994,149:295–305. 4. De Nicola A and Sucre MJ. Critical Care 2009, 13(Suppl non solo in centri specializzati, ma 1):P202 diffusamente in tutte le rianimazioni.
MINERVA ANESTESIOLOGICA Vol. 79, Suppl. 1 al N. 10, 2013
SDRA Y LESIONES PULMONARES ASOCIADAS A VENTILACIÓN MECÁNICA LFVVECCO2-R TO PROVIDE "LUNG REST" IN LESIONS OF RESPIRATORY SYSTEM: EXPERIENCE IN ONE PATIENT Pastore A, Pagnucci N, Giunta M, Martinelli R, Forfori F, Giunta F. AOUP, Anestesia e Rianimazione IV, Stabilimento di Cisanello Direttore: Prof. Francesco Giunta BACKGROUND: alcune condizioni, come la fistola bronco-pleurica, la rottura di trachea o la lesione diaframmatica, risentono del continuo susseguirsi delle fasi di inspirazione ed espirazione legate all’ attività toracica; inoltre, il raggiungimento di elevati valori pressori nelle vie aeree durante il supporto ventilatorio influisce negativamente sul danno già esistente. OBIETIVI: nella nostra esperienza, abbiamo utilizzato il supporto extra- corporeo di rimozione della CO2, con sistema veno-venoso a bassi flussi (LFVVCCO2-R, ProLUNG, ESTOR Spa), in associazione a parametri di ventilazione minimamente aggressivi, con l’ obiettivo di ottenere la “messa a riposo” del polmone. DESCRIZIONE: abbiamo reclutato un paziente HIV+, il quale, all’ ingresso in UTI, presentava uno pneumotorace da P. carinii, estesosi poi bilateralmente, con comparsa di una fistola bronco-pleurica.
PaO2 PaCO2 Sesso Età Diagnosi pH SAPS II SOFA Murray score (mmHg) (mmHg)
M 40 Pnx da P. carinii in pz HIV+ 7,43 83 35 38 5 2,5
180 160 160 140 140 120 120
100 100 80 80 PaO2 mmHg 60 60 PaCO2 40 40 20 20 0 0 IOT (ventilaz protettiva - FiO2 50%, Vt Ventilaz ultra-protettiva (FiO2 45%, Vt 6ml/kg, FR 30/min, PEEP 7cmH20) 3ml/kg, FR 30/min, ZEEP) + LFVVECCO2R
DISCUSSIONE: LFVVECCO2-R ha consentito l’ applicazione di una ventilazione ultra-protettiva, grazie alla rimozione della CO2 e alla prevenzione dell’ acidosi respiratoria. In tal modo, è stata ottenuta la guarigione delle lesioni polmonari, con dimissione del paziente a distanza di una settimana dal trattamento.
CONCLUSIONI: LFVVECCO2-R può costituire un valido supporto in pazienti con adeguati scambi gassosi, ma portatori di lesioni a carico del sistema respiratorio che richiedono una sorta di “pausa” nell’ attività toracica per poter guarire. ProLUNG – Estor Spa
CORRESPONDENCE
2. Griesenbach U, Alton EW; UK Cystic Fibrosis Gene Therapy Consortium. In patients who fail weaning from mechanical ventilation, Gene transfer to the lung: lessons learned from more than 2 decades – the increase in respiratory muscle effort may quickly lead to of CF gene therapy. Adv Drug Deliv Rev 2009;61:128 139. respiratory muscle fatigue and pump failure (4). This prospective 3. Alton EW, Armstrong DK, Ashby D, Bayfield KJ, Bilton D, Bloomfield EV, Boyd AC, Brand J, Buchan R, Calcedo R, et al.; UK Cystic Fibrosis physiological pilot investigation aimed to examine the hypothesis Gene Therapy Consortium. Repeated nebulisation of non-viral CFTR that sharing CO2 extraction between the minute ventilation provided gene therapy in patients with cystic fibrosis: a randomised, double- by the respiratory muscles alone and the extracorporeal flow blind, placebo-controlled, phase 2b trial. Lancet Respir Med [online provided by ECCO2R in the absence of respiratory acidosis may ahead of print] 3 Jun 2015; DOI: 10.1016/S2213-2600(15)00245-3. 4. Davies JC, Gill D, Griesenbach U, Voase N, Davies G, Higgins T, Innes JA, result in a substantial reduction of respiratory muscle effort in Boyd C, Porteous D, Hyde S, et al. Evaluation of safety and gene patients who fail weaning from mechanical ventilation. Clinical trial expression with single dose of pGM169/GL67A administered to the nose registered with www.clinicaltrials.gov (NCT 02259335). and lung of individuals with CF: the UK CF Gene Therapy Consortium Pilot Study [abstract]. Pediatr Pulmonol 2009;(Suppl 32):305. 5. Davies JC, Gill D, Griesenbach U, Voase N, Davies G, Higgins T, Innes Methods JA, Boyd C, Porteous D, Hyde S, et al. Evaluation of safety and gene Four consecutive patients with chronic obstructive pulmonary expression with single dose of pGM169/GL67A administered to the disease (FEV =246 17% predicted) invasively ventilated for 9 6 3 nose and lung of individuals with CF: the UK CF Gene Therapy 1 Consortium Pilot Study [abstract]. Thorax 2009;64:A70. days for acute hypercapnic respiratory failure refractory to NIV 6. Hyde SC, Pringle IA, Abdullah S, Lawton AE, Davies LA, Varathalingam were studied after giving written informed consent. The local A, Nunez-Alonso G, Green AM, Bazzani RP, Sumner-Jones SG, et al. institutional review board approved the protocol. CpG-free plasmids confer reduced inflammation and sustained Inclusion criteria were at least two unsuccessful T-piece weaning – pulmonary gene expression. Nat Biotechnol 2008;26:549 551. trials and persistence of hypercapnia during invasive mechanical 7. Gill DR, Smyth SE, Goddard CA, Pringle IA, Higgins CF, Colledge WH, Hyde SC. Increased persistence of lung gene expression using ventilation. Exclusion criteria are reported in the online supplement. plasmids containing the ubiquitin C or elongation factor 1alpha On the morning of the study, the patients underwent a T-piece weaning promoter. Gene Ther 2001;8:1539–1546. trial. If they did not pass the trial, the patients were reconnected for 8. McLachlan G, Davidson H, Holder E, Davies LA, Pringle IA, Sumner- a minimum of 2 hours to the ventilator, until they restored the previous Jones SG, Baker A, Tennant P, Gordon C, Vrettou C, et al. Pre-clinical evaluation of three non-viral gene transfer agents for cystic fibrosis gas exchange. Afterward, they repeated the trial with the addition after aerosol delivery to the ovine lung. Gene Ther 2011;18:996–1005. of the ECCO2R (ProLung; Estor, Pero, Italy), started just 5 minutes 9. Davies LA, Nunez-Alonso GA, McLachlan G, Hyde SC, Gill DR. Aerosol before the suspension of ventilation. At the end of the latter trial, they delivery of DNA/liposomes to the lung for cystic fibrosis gene therapy. could be extubated under ECCO2R if the predefined extubation criteria – Hum Gene Ther Clin Dev 2014;25:97 107. were fulfilled. The ECCO2R was continued until all the following 10. Kent L, Reix P, Innes JA, Zielen S, Le Bourgeois M, Braggion C, Lever S, Arets HG, Brownlee K, Bradley JM, et al.; European Cystic criteria were stable for at least 12 hours: respiratory rate lower than
Fibrosis Society Clinical Trial Network (ECFS-CTN) Standardisation 25 breaths/min, pH higher than 7.35, PaCO2 lower than 20% of baseline, Committee. Lung clearance index: evidence for use in clinical trials in and absence of signs of respiratory distress. cystic fibrosis. J Cyst Fibros 2014;13:123–138. Changes in esophageal, gastric, and transdiaphragmatic pressures 11. Rose AC, Goddard CA, Colledge WH, Cheng SH, Gill DR, Hyde SC. and pressure at the airway opening were measured as previously Optimisation of real-time quantitative RT-PCR for the evaluation of non- viral mediated gene transfer to the airways. Gene Ther 2002;9:1312–1320. described (5). Inspiratory pulmonary resistance and elastance were assessed using Mead and Whittenberger’s technique (6). Dynamic Copyright © 2015 by the American Thoracic Society intrinsic positive end-expiratory pressure was measured (5), and the pressure time integrals of the diaphragm and esophageal pressures per minute were calculated (7). Inspiratory work of breathing performed Effects of Extracorporeal CO2 Removal on Inspiratory by the patient was computed from esophageal pressure/tidal volume Effort and Respiratory Pattern in Patients Who Fail loops as previously described (8). Equipment dead space was 134 ml. Weaning from Mechanical Ventilation The CO2 removal rate was calculated on the basis of internal fl fi measurements of CO2 percentage and ow in the hollow- ber To the Editor: membrane sweep gas. Arterial blood gases together with the dyspnea score using In patients with acute respiratory failure, severe respiratory acidosis is the Borg scale were taken at the beginning and at the end of both managed by either invasive or noninvasive ventilation (NIV). Recent T-piece weaning trials. data suggest that mechanical ventilation may be supported by extracorporeal CO2 removal (ECCO2R) to manage the severe Results respiratory acidosis consequent to superprotective ventilatory strategies All four patients who failed the first T-piece trial (49 6 6 minutes) in patients with acute respiratory distress syndrome (1) or failure of were able to successfully pass the second one when connected NIV in patients with acute hypercapnic respiratory failure (2, 3). to the ECCO2R circuit and were extubated. All but one remained without mechanical ventilation for 48 hours; ECCO2R was suspended after 52 6 3 hours. One patient needed to be Author Contributions: L.P., M.V.R., and S.N. contributed to conception, design, analysis, and interpretation and to drafting the manuscript. L.F. contributed to reintubated after 4 hours for stridor and glottic edema. All patients design, analysis, and interpretation. N.C. contributed to design, analysis, and tolerated the procedure well, but one required a change in the interpretation. V.C. and A.G. contributed to analysis and interpretation. catheter site after 10 hours as a result of the catheter occlusion. This letter has an online supplement, which is accessible from this issue’s Mean blood flow through the extracorporeal circuit was 320 6 56 table of contents at www.atsjournals.org ml/min with a CO2 removal of 78 6 18 ml/min. Table 1 shows
1392 American Journal of Respiratory and Critical Care Medicine Volume 192 Number 11 | December 1 2015 Correspondence CORRESPONDENCE
Table 1. Inspiratory Effort, Lung Mechanics, and Work of Breathing in Patients Undergoing a T-Piece Trial with and without ECCO2R
Pdi Swing PTPdi/min PTPes WOB/min PEEPi,dyn EL RL (cm H2O) (cm H2O $ s/min) (cm H2O $ s/min) (J/min) (cm H2O) (cm H2O/L) [cm H2O/(L $ s)] T-Piece T-Piece T-Piece T-Piece T-Piece T-Piece T-Piece T-Piece T-Piece T-Piece T-Piece T-Piece T-Piece T-Piece without with without with without with without with without with without with without with ECCO2R ECCO2R ECCO2R ECCO2R ECCO2R ECCO2R ECCO2R ECCO2R ECCO2R ECCO2R ECCO2R ECCO2R ECCO2R ECCO2R
Patient #1 T0 5.6 5.2 124 111 111 92 5.3 5.9 2.6 2.6 16.2 16.8 9.9 10.6 T1 7.5 4.4 186 95 156 74 8.2 5.3 2.8 2.4 18.3 17.4 12.4 8.5 Δ ↑1.9 ↓0.8 ↑62 ↓16 ↑45 ↓18 ↑2.9 ↓0.6 ↑0.2 ↓0.2 ↑2.1 ↑0.6 ↑2.5 ↓2.1
Patient #2 T0 4.8 5.0 98 105 77 80 4.9 5.4 1.5 1.8 13.6 12.3 7.5 7.9 T1 6.5 4.1 177 98 162 68 7.7 5.2 2.2 1.8 13.4 13.5 8.2 6.9 Δ ↑1.7 ↓0.9 ↑79 ↓7 ↑85 ↓12 ↑2.8 ↓0.2 ↑0.7 0 ↓0.2 ↑1.2 ↑0.7 ↓1 Patient #3 T0 10.9 11.5 220 234 198 199 9.8 10.3 4.8 5.2 17.5 17.1 15.7 16.3 T1 14.7 7.1 392 156 354 136 15.3 8.4 6.1 3.2 16.8 17.0 19.2 12.8 Δ ↑3.8 ↓4.4 ↑172 ↓78 ↑156 ↓63 ↑5.5 ↓1.9 ↑1.3 ↓2 ↑0.7 ↓0.1 ↑3.5 ↓3.5 Patient #4 T0 9.5 8.6 191 180 166 161 8.4 7.9 4.4 4.8 16.9 16.4 12.4 16.4 T1 14.7 5.3 325 144 292 126 14.0 6.6 6.0 2.0 18.2 17.7 18.3 16.6 Δ ↑5.2 ↓3.3 ↑134 ↓36 ↑126 ↓35 ↑5.6 ↓1.3 ↑1.6 ↓2.8 ↑1.3 ↑1.3 ↑5.9 ↑0.2
Definition of abbreviations: Δ = absolute difference between values over time (from T0 to T1); ↑ = increase; ↓ = decrease; EL = inspiratory pulmonary elastance; ECCO2R = extracorporeal CO2 removal; Pdi swing = tidal transdiaphragmatic pressure; PEEPi,dyn = dynamic positive end-expiratory pressure; PTPdi/min = the pressure time integrals of the diaphragm per minute; RL = inspiratory pulmonary resistance; T0 = beginning of the T-piece trial; T1 = end of the T-piece trial; WOB = work of breathing expressed as power. 1393
CORRESPONDENCE that all indices of the diaphragm and inspiratory muscle effort Marco V. Ranieri, M.D. were decreased at the end of the T-piece trial with ECCO2R. Universita ` “La Sapienza” di Roma Table E1 in the online supplement illustrates the individual data Rome, Italy of breathing pattern, arterial blood gasses, and dyspnea. Stefano Nava, M.D. Alma Mater University Discussion Bologna, Italy This pilot physiological report demonstrates that in patients with chronic obstructive pulmonary disease who are not yet ready to be weaned, the addition of ECCO2R during unsupported References breathing avoids the increase in PaCO2 and inspiratory effort and the occurrence of a rapid shallow breathing pattern. 1. Terragni PP, Del Sorbo L, Mascia L, Urbino R, Martin EL, Birocco A, Faggiano C, Quintel M, Gattinoni L, Ranieri VM. Tidal volume lower The inability to sustain spontaneous breathing in patients with than 6 ml/kg enhances lung protection: role of extracorporeal carbon chronic obstructive pulmonary disease is the result of an imbalance dioxide removal. Anesthesiology 2009;111:826–835. between the load and the capacity of the respiratory muscles to 2. Del Sorbo L, Pisani L, Filippini C, Fanelli V, Fasano L, Terragni P, Dell’Amore generate pressure. This results in higher respiratory rates, leading A, Urbino R, Mascia L, Evangelista A, et al. Extracorporeal CO2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched to dynamic hyperinflation, elevated intrathoracic pressures, – fi cohort study with historical control. Crit Care Med 2015;43:120 127. excessive work of breathing, and nally CO2 retention (4). These 3. Burki NK, Mani RK, Herth FJ, Schmidt W, Teschler H, Bonin F, Becker H, changes may occur either during an acute exacerbation or when Randerath WJ, Stieglitz S, Hagmeyer L, et al. A novel extracorporeal the patient is not yet ready to be weaned from the ventilator (9, 10). CO(2) removal system: results of a pilot study of hypercapnic respiratory – Adding ECCOR to NIV may avoid intubation in those patients failure in patients with COPD. Chest 2013;143:678 686. 4. Tobin MJ, Laghi F, Brochard L. Role of the respiratory muscles in acute in whom NIV fails to manage severe respiratory acidosis. The respiratory failure of COPD: lessons from weaning failure. J Appl underlying physiological mechanism evoked to explain these data was Physiol (1985) 2009;107:962–970. fi the ef cacy of ECCO2R to remove the excess of CO2 that could not be 5. Appendini L, Purro A, Patessio A, Zanaboni S, Carone M, Spada E, managed by conventional NIV. In the present investigation, we have Donner CF, Rossi A. Partitioning of inspiratory muscle workload and pressure assistance in ventilator-dependent COPD patients. shown that ECCO2R may be indicated in patients with increased Am J Respir Crit Care Med 1996;154:1301–1309. work of breathing, even in the absence of respiratory acidosis. 6. Mead J, Whittenberger JL. Physical properties of human lungs measured The reduction in inspiratory effort likely lowers CO2 during spontaneous respiration. JApplPhysiol1953;5:779–796. production of the respiratory muscles, which can be quite high in 7. Sassoon CS, Light RW, Lodia R, Sieck GC, Mahutte CK. Pressure-time such patients, contributing to a reduction in total CO production. product during continuous positive airway pressure, pressure support 2 ventilation, and T-piece during weaning from mechanical ventilation. Under these circumstances, the CO2 removal achieved by ECCO2R Am Rev Respir Dis 1991;143:469–475. may be sufficient to reduce ventilator demand to the point 8. Brochard L, Harf A, Lorino H, Lemaire F. Inspiratory pressure support where spontaneous unassisted breathing is possible. prevents diaphragmatic fatigue during weaning from mechanical LimitationsofthestudyincludetheshortdelaybetweenthetwoT- ventilation. Am Rev Respir Dis 1989;139:513–521. 9. Laghi F, Topeli A, Tobin MJ. Does resistive loading decrease piece trials, which may not have allowed full recovery (9). In contrast, diaphragmatic contractility before task failure? J Appl Physiol (1985) weaning failure was not associated with diaphragmatic fatigue in 1998;85:1103–1112. similarpatients(10).Anotherconcernisthatthesequenceofweaning 10. Laghi F, Cattapan SE, Jubran A, Parthasarathy S, Warshawsky P, Choi trials was not randomized, so that exclusion of a time effect to explain YS, Tobin MJ. Is weaning failure caused by low-frequency fatigue of – the improvement in respiratory parameters during the second trial the diaphragm? Am J Respir Crit Care Med 2003;167:120 127. cannot be excluded. However, this seems less likely, considering that the baseline physiological variables were almost identical between Copyright © 2015 by the American Thoracic Society the trials. We hope these results encourage future investigations on the use ECCO2R to facilitate the weaning process. n Lung Cancer Susceptibility, Ethnicity, and the Benefits Author disclosures are available with the text of this letter at of Computed Tomography Screening www.atsjournals.org. To the Editor Lara Pisani, M.D. : Alma Mater University Bologna, Italy In the editorial accompanying a post hoc analysis of the National Lung Screening Trial (NLST) (1), for which the lung cancer–specific Luca Fasano, M.D. mortality reduction from computed tomography (CT) screening Sant’Orsola Malpighi Hospital Bologna, Italy was 39 and 14% in African American and white subjects, respectively, Ruparel and Navani focus almost exclusively on health Nadia Corcione, M.D. inequalities (2). However, we are intrigued by the magnitude of Vittoria Comellini, M.D. this “ethnicity-based” mortality benefit and its relevance to lung Alma Mater University Bologna, Italy cancer susceptibility in the context of screening outcomes (3).
Aldo Guerrieri, M.D. Sant’Orsola Malpighi Hospital Supported by grants from the University of Auckland, Health Research Bologna, Italy Council of New Zealand, and Synergenz BioSciences Ltd. (R.P.Y.).
1394 American Journal of Respiratory and Critical Care Medicine Volume 192 Number 11 | December 1 2015 Introduction Case report
Use of lung-protective strategies may complicate We report the case of a 47-year-old, AH1N1- patient management, motivating alternative infected man, who was admitted to our ICU methods for better lung-replacement approaches. because of rapidly developing respiratory failure. We describe the ability of a novel extracorporeal The patient was in extremely severe condition, venovenous CO2 removal device to reduce minute deeply unconscious (GCS 5), hypotonic, anuric and ventilation while maintaining normocarbia in a required artificial lung ventilation with 100% case of severe ARDS complicating type A (H1N1) oxygen. The chest angio-CT did not demonstrate influenza. features of pulmonary embolism yet ARDS-like changes were visible. Conventional ventilation, antibiotics and antiviral therapy did not improve the patient's condition. The patient was
hypercapnic (PaCO2 145 mm Hg/19 kPa), acidotic (pH 6.95) and hyperkinetic (HR 130 min-1, CO 13.1 L min-1). Total lung compliance was 22 mL cm H2O-1, and SAP/DAP was 65/40 mm Hg). The
PaO2/FIO2 index was 90. The influenza A/H1N1 infection was confirmed using the RT-PCR method. On day 3, conventional PCV was re-established at
FIO2 = 0.55%. The change of ventilation mode resulted in another increase in PaCO2 to 68.5 mm Hg (9.13 kPa), decrease in pH to 7.21 and deteriorated blood oxygenation (PaO2 decrease to 57 mm Hg/7.72 kPa and SaO2 to 89.1%). The
planning for extracorporeal CO2 removal were started. The double-lumen dialysis catheter, 14F, 22 cm long, was introduced to the femoral vein
and the system for low-flow extracorporeal CO2 removal was connected (ProLUNG™, Estor, Italy). The system has a negligible extracorporeal volume Procedure of 120mL per line, which through a small dimension vascular venous access and a blood flow of less than 450mL/min is aimed at reducing The procedure was carried out with the flow of the hemodynamic impact on the patient. This 400 mL min-1 of heparinized blood. During day 1 system allows also to adjust the airflow and to of extracorporeal CO2 removal, PaCO2 markedly warm the air to a temperature below 37° C. decreased to 50-60 mm Hg (6.8-9 kPa), pH increased to 7.3 -7.36 and blood oxygenation
improved (PaO2 82 mm Hg/11.1 kPa, SaO2 96%). The bi-level mechanical ventilation was carried Discussion out according to the lung-sparing approach: FIO2 60 %, PEEP 14 cm H2O (1.4 kPa), PIP 30 cm H2O (3 kPa), obtaining the tidal volume of 4-6 mL kg- 1. Viral infections are especially difficult to treat. This The treatment was continued for 132 hours, case report indicated that the use of using only 3 filters, resulting in a marked extracorporeal CO2 removal, when compared with improvement in gas exchange and weaning from standard therapy, can be beneficial in complicated artificial ventilation after 16 days. The patient cases of AH1N1 influenza. ProLUNG™ may be an eventually recovered and discharged after 23 effective lung-protective adjunct to mechanical days ventilation.
MINERVA ANESTESIOLOGICA Vol. 79, Suppl. 1 al N. 10, 2013 Usefulness of a VV extracorporeal CO2 removal device (Prolung R) in severe pneumonia complicated by refractory bronchospasm Visconti F 1, Jeong Chul K 2, Marafon S1, Fornasier L 1 , Primadei M 1, Ronco C 2 , Piccinni P 1
1 – Department of Anaesthesia and Intensive Care, San Bortolo General Hospital, Vicenza; 2 - Department of Nephrology, San Bortolo General Hospital and International Renal Research Institute, Vicenza, Italy Background Results and Discussion
We will report on the case of a 68 year old woman, admitted to our ICU after the surgical repair of a ruptured AAA. Her post- operative course seemed uneventful, but on post-op day 3 it was complicated by an acute respiratory distress. She failed NIV support and needed invasive ventilation; her CXR showed a right lobar pneumonia ( Fig. 1, 2). Her oxygenation was seriously impaired ( PaO 2/FiO 2 ratio < 200) and she developed a severe bronchospasm, refractory to maximal medical therapy. Blood gas analysis showed a profound respiratory acidosis, with
PaCO 2>105 mmHg. After consulting the attending Nephrologist, a novel kind of VV - ECCO 2 removal device (PROLUNG, ESTOR SpA, Milano, Italy ) was considered.
Graph 1 Trends in arterial PaO2 and PaCO2 during the ICU stay
Despite maximal medical treatment, the patient needed an advanced ventilatory management, with low Tidal volumes (5- 6 ml/kg), high PEEP level, 5 cycles of pronation. Her oxygenation gradually improved and, after 7 days, she was extubated to NIV ( PSV – a cycle of 4 hours). The PROLUNG support was continued for many hours after the extubation and proved able to support a potentially stressful time for our Fig 1 Initial CxR finding Fig. 2 - 2 days before the extubation patient. She fully recovered and was transferred to an intermediate ward ( Pneumology) for monitoring. In graph 1, it is possible to see the timing of Prolung support, Methods and the changes in blood gases, as measured in arterial blood
samples. After the institution of extracorporeal CO 2 removal, ProLUNG is a minimally invasive, extracorporeal, hemodynamic there was a sudden drop in arterial PaCO2 ( First arrow). Four treatment for the removal of excessive CO2 in patients with days later, the support was gradually reduced ( Second arrow); respiratory acidosis. The system has a small extracorporeal the Qb and the O2 flow were halved, with no evidence of volume of 120mL per line, which through a small dimension impact on global gas exchange ( lung function was improving). vascular venous access and a blood flow of less than 450mL/min After the discontinuation of PROLUNG support, arterial is aimed at reducing the hemodynamic impact on the patient. This PaCO 2 remained stable, as the bronchospasm had solved. system does not provide an internal control system or monitor of Interestingly, in this graph we can see some spikes in PaO 2, air flow or variations in pH and pCO2 that may occur in the direct consequence of cyclical pronation. patient during this treatment. Therefore, these parameters must be contemporarily analyzed using standard techniques. Conclusions The pre-existing medical therapy continued during the extracorporeal support. Blood gas exchange was closely PROLUNG proved effective in solving a severe, refractory monitored using capnography and serial blood gas analysis. A hypercapnia with profound acidosis. The extracorporeal double lumen 14 Fr catheter was placed in the right femoral vein support allowed a more protective ventilation, preventing under real-time ultrasound guidance. PROLUNG was connected barotrauma/volutrauma and subsequent iatrogenic damage to to the patient and primed, a continous infusion of eparine was lung parenchyma. It was possible to focus our ventilatory instituted. The initial parameters were : Qb 380 ml/min, O2 flow support on the impaired oxygenation, while PROLUNG solved 14 L/min; a fast and stable reduction in EtCO 2 and PaCO 2 (from the respiratory acidosis and its possible consequences. There 105 to 50 mmHg) was observed, with no signs of hemodynamic were not systemic complications of extra-corporeal support, compromise nor instability. These parameters were halved with hemodynamic stability was fully preserved, and there were not the improvement of the disease ( see Graph 1, discussion for significant episodes of bleeding or thrombosis. The treatment explanation). was instituted very soon after the prescription, with excellent results.
TRASPLANTE PULMONAR
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Biblioteca richiedente: Dipartimento di Scienze Cardiovascolari Respiratorie Nefrologiche Anestesiologiche e Geriatriche
Data richiesta: 13/07/2015 11:50:37
Biblioteca fornitrice: Biblioteca Dir Scientifica IRCCS Fondazione Policlinico San Matteo - Pavia
Data evasione: 13/07/2015 11:54:07
Titolo rivista/libro: European journal of anaesthesiology (Online)
Titolo articolo/sezione: How to minimise ventilator-induced lung injury in transplanted lungs: The role of protective ventilation and other strategies.
Autore/i: Soluri-Martins A,Sutherasan Y, Silva PL, Pelosi P, Rocco PR.
ISSN: 1365-2346
DOI:
Anno: 2015
Volume: jul
Fascicolo: 2
Editore:
Pag. iniziale:
Pag. finale:
Case report
SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES 2016; 33; 186-190 © Mattioli 1885
Successful management of acute respiratory failure in an Idiopathic Pulmonary Fibrosis patient using an extracorporeal carbon dioxide removal system
Andrea Vianello, Giovanna Arcaro, Luciana Paladini, Silvia Iovino Respiratory Intensive Care Unit, University-City Hospital of Padova, Padova, Italy
Abstract. Patients with Idiopathic Pulmonary Fibrosis (IPF) requiring Invasive Mechanical Ventilation (IMV) following unsuccessful treatment with Non-Invasive Ventilation (NIV) have a high mortality rate. IMV is, moreover, an independent predictor of poor outcome during the post-transplantation period in patients on waiting lists for Lung Transplantation (LT). Here we describe the successful management of an IPF patient with acute respiratory failure (ARF) using a pump-assisted veno-venous system for extracorporeal CO2 removal (EC-
CO2R) (ProLUNG® system) as an alternative to endotracheal intubation (ETI) following NIV failure. Given this positive experience, further studies are warranted focusing on the ECCO2R system’s tolerability, safety, and efficacy in patients with IPF and severe ARF in whom NIV alone is ineffective. (Sarcoidosis Vasc Diffuse Lung Dis 2016; 33: 186-190)
Key words: Idiopathic Pulmonary Fibrosis, extracorporeal CO2 removal, acute respiratory failure
Introduction port and admission to an Intensive Care Unit (ICU) (2). Causes of acute deterioration include conditions Accounting for nearly 30% of Lung Transplan- such as pneumonia, pulmonary embolism, conges- tation (LT) procedures performed worldwide, Idi- tive heart failure, and pneumothorax; the term “acute opathic Pulmonary Fibrosis (IPF) is a chronic, pro- exacerbation of IPF” was formulated to describe an gressive and generally fatal interstitial lung disease acute respiratory deterioration without an identifi- of unknown aetiology that causes death in nearly all able cause (3,4). patients within 6 years of diagnosis (1). Although Some observational studies have reported that most IPF patients die from slowly progressive res- Non-Invasive Ventilation (NIV) can efficaciously piratory failure, a small minority (approximately treat IPF patients who develop acute respiratory fail- 5-10%) develop transient acute respiratory worsen- ure (ARF) requiring ventilatory assistance and pre- ing and/or failure that may require ventilatory sup- vent intubation (5,6); NIV application is, neverthe- less, associated with a marked failure risk, and high mortality rates have been reported in IPF patients Received: 30 August 2015 who require Invasive Mechanical Ventilation (IMV) Accepted after revision: 22 December 2016 Correspondence: Andrea Vianello, MD following NIV failure (7). U.O. Fisiopatologia Respiratoria A recently introduced procedure, Extracorpor- Azienda Ospedaliera di Padova eal CO2 removal (ECCO2R) has been proposed as Via Giustiniani, 1 - 35128 Padova (Italy) Tel. 0039-049-8218587 an intervention to eliminate CO2 from the blood of Fax: 0039-049-8218590 patients undergoing NIV who are unable to achieve E-mail: [email protected] adequate gas exchange at maximal tolerable ventila- Extracorporal carbon dioxide removal in Idiopathic Pulmonary Fibrosis 187
tion pressures in the attempt to avoid IMV and its creased (1716 pg/mL). A chest X-ray revealed bilat- complications. Sporadic case reports and case series eral, reticular, coarse linear shadows. Blood cultures have reported that ECCO2R systems have been used for pathogenic bacteria or fungi and serologic tests efficaciously in some cases of acute exacerbation of against major pneumotropic agents were all nega- COPD (8-10), bronchiolitis obliterans (11) severe tive; but in view of the fact that a bronchoscopy was bronchial asthma (12), as well as non-Cystic Fibrosis not feasible and acute bacterial infection could not (CF) bronchiectasis (13). be confidently excluded, the patient was prescribed Despite increasing interest in the use of EC- intravenous antibiotic therapy (piperacillin and
CO2R systems in patients who develop refractory levofloxacin); he was also prescribed prednisone (1 hypercapnic ARF, its utility in IPF patients in the mg·kg−1 per day) and diuretics. event of ARF has never been assessed. This report Since ventilatory assistance was necessary, NIV describes the successful management of an IPF pa- was initiated using a portable ventilator (Elisée 150, tient with ARF who was treated efficaciously with ResMed Poway, CA, USA) set on the Pressure Sup-
ECCO2R following NIV failure. port Ventilation (PSV) mode. The PSV was initially titrated to a moderate tidal volume (6-8 mL/kg); the ventilator setting was then readjusted according to Case Report arterial blood gas (ABG) values; we aimed to main-
tain arterial oxygen saturation (SaO2) over 90% and A 73-year-old male was admitted to the Respir- partial pressure of carbon dioxide in arterial blood atory Intensive Care Unit (RICU) of the University- (PaCO2) at approximately 50 mmHg and to reduce City Hospital of Padova (Italy) for acute respiratory the RR. The initial PS level did not exceed 20 cm failure (ARF). In accordance with the American H2O and was progressively elevated by 1-2 cmH2O
Thoracic Society/European Respiratory Society con- without exceeding 30 cm H2O due to the high risk sensus statement criteria, the patient was disagnosed of pneumothorax. Positive End Expiratory Pressure with IPF (at the age of 70) on the basis of High- (PEEP) was set at 6 cmH2O to obtain the best oxy- Resolution CT (HRCT) findings (4). The patient genation with minimal haemodynamic side effects, presented at the Emergency Department complain- and the levels were raised by 1-2 cmH2O without ing of increasing difficulty breathing and produc- exceeding 6-8 cm H2O. Supplemental oxygen was tive cough during the preceding week and reported added to the ventilator circuit. The patient was con- suffering from recurrent episodes of ARF over the nected to the ventilator by means of a full face mask; preceding 2 years. He was receiving treatment with colloid dressings were placed on the major pressure pirfenidone therapy and long-term oxygen therapy points to minimize skin injury. NIV was delivered (LTOT) with nocturnal NIV. He was also receiving continuously except for brief “rest” (30-60 min) peri- steroid therapy during the four days preceding ad- ods to allow the patient to receive dietary liquid sup- mittance. He was admitted to the Emergency De- plements and to speak. A standard ICU monitoring partment of our hospital due to worsening of the system displaying electrocardiographic data, pulse clinical condition and was transferred to the RICU. oximetry, invasive blood pressure, and RR measure- At admission to our unit the patient was polyp- ments was utilized. neic, fatigued and moderately sleepy. Physical exami- A HRCT, performed 3 days after admission, nation revealed tachypnea [Respiratory Rate (RR): showed honeycombing pattern and traction bron- 26b/min], weak productive cough, and diffuse sub- chiectases predominantly of the lower lobes; new or crepitant bilateral rales. He was severely hypercapnic progressive infiltrates were not evident (Figure 1). during supplemental oxygen therapy and his arterial Despite continuous use of NIV, pulmonary gas blood gas (ABG) values were: pH, 7.32; PaCO2, 69.4 exchange progressively deteriorated: on day 4 after mmHg; PaO2, 95 mmHg; HCO3-, 35.1 mmol/L; admission ABG levels showed increasingly severe
PaO2/FiO2 ratio: 190. A complete hematological hypercapnia (pH, 7.39; PCO2, 80 mmHg; PaO2, 79 work-up revealed mild anemia (Hb 12.5 g/L) and mmHg, during assisted ventilation). The patient also leukocytosis (WBC: 18,830 x 106/L); serum elec- showed signs of exhaustion (RR was 30 to 35), in- trolytes were normal. NT-proBNP was slightly in- creasing intolerance to uninterrupted NIV and an 188 A. Vianello, G. Arcaro, L. Paladini, et al.
and connected to the extracorporeal circuit. The blood flow was initiated through the circuit by a centrifu- gal pump at 300 ml/min. The oxygen flow through the gas exchanger was initiated at 12 L/min to maxi-
mize CO2 removal. In accordance with study protocol guidelines for anticoagulation, the patient was started on an intravenous heparin infusion to maintain an ac- tivated clotting time between 150 and 180 seconds.
The amount of CO2 removed by the device was adjusted depending on the ABG and RR lev- els, which were measured every 4 hours. During use, the ProLUNG® circuit blood flow varied from 300 to 450 mL/min; the remainder of gas exchange occurred through the lungs using NIV adjusted to
releasing low VT (6-8 mL/kg) with a low/moderate PEEP level.
PaCO2 decreased after ECCO2R therapy was initiated from 71 before cannulation to 50mmHg Fig. 1. Chest high-resolution computed tomography (HRCT) within 24 hours; the patient’s RR also decreased from images taken at the patient’s third day of hospitalization in the Respiratory Intensive Care Unit (RICU) 30 to 20-22 b/min. PaCO2 subsequently remained within a 52 to 48 mm Hg range for the duration of therapy (Figure 2). The patient’s clinical status pro- imminent need for IMV. Concerned about the high risk of complications linked to IMV, we informed the patient about an alternative veno-venous extra- corporeal carbon dioxide removal (ECCO2R) meth- od, which had already been approved for an investi- gational feasibility study by our local ethics commit- tee, that was available in our hospital. He was also provided detailed information about the benefits and risks of that system.
The ECCO2R device used in our center is the ProLUNG® system, a pump-driven veno-venous system which utilizes a small single veno-venous dual lumen catheter (size=13 Fr) that can be inserted into a femoral or jugular vein. It is characterized by a low blood flow rate (up to a maximum of 450mL/ min) and a single-use-only gas exchange cartridge consisting of a hollow fiber polypropylene diffusion membrane network with an effective surface area of 1.35m2. As the device uses a total volume circuit of only 120 mL, the hemodynamic impact on the patient is minimized. Oxygen flows as a carrier gas within the hollow fibers, and CO2 moves by selective diffusion across the concentration gradient from the blood. The patient freely gave consent to receiving treat- ment with the device. With the patient in a supine position, a 13 Fr catheter was inserted percutaneously 2 2 Fig. 2. Variations in the patient’s PaCO2, PaO /FiO ratio and through the right femoral vein without complication Respiratory Rate values after ECCO2R was initiated Extracorporal carbon dioxide removal in Idiopathic Pulmonary Fibrosis 189
gressively improved over the next 3 days, making it dependent predictor of a longer time on IMV and possible to reduce NIV application from continuous in the ICU during the post-transplantation period, use, except for brief “rest” periods, to 3-4 hours off managing IPF patients on waiting lists for LT using the ventilator by day 3. By day 4, the patient was able an ECCO2R system to avoid IMV could prove to be to breathe without ventilatory support for 10 con- particularly important (17). secutive hours; on the same day, the patient was in- Although extracorporeal support devices them- creasingly active, clinically stable, and extracorporeal selves are linked to some complications, such as ves- support was suspended. The catheter was removed, sel perforation, bleeding, and infections (18), those coagulation values were normal, and there was no risks were minimized in our case by using a minimal- additional bleeding. Subsequently, the patient con- ly invasive, well tolerated CO2 removal system that is tinued to receive NIV at night. There were no com- based on veno-venous cannulation as opposed to the plications during or after ECCO2R. On day 7, the traditional veno-arterial cannulation with insertion patient was transferred to the Pulmonary Division in of a a small single veno-venous dual lumen catheter. good clinical condition; he was mildly hypercapnic Since the device, which does not require any special- during supplemental oxygen therapy and his ABG ized staff/training, proves easy to use, it is presum- values were: pH, 7.48; PaCO2, 46.9 mmHg; PaO2, able that it could be safely utilized in any medical or
82 mmHg; HCO3-, 34.5 mmol/L; PaO2/FiO2 ratio: surgical ICU. 314.3. When he was discharged from hospital he was In conclusion, given this and other positive ex- prescribed night-time ventilation via a nasal mask. periences outlined in the literature in patients affect- ed with a variety of conditions, further studies are
warranted to verify the ECCO2R system’s tolerabil- Discussion ity, safety, and efficacy in IFP patients with refractory hypercapnic ARF, with special regard to candidates A major cause of morbidity and mortality, tran- awaiting LT. sient ARF, which leads to a high percentage of hos- pital admissions and up to 40% of all deaths, is a well known occurrence in IPF patients (14,15). When This work was performed at the Padova Univer- it presents, most patients develop hypercapnia and sity-City Hospital, Padova, Italy require ventilatory assistance: unfortunately, due to gross abnormalities in pulmonary mechanics such as alterations of the elastance of the lungs (16), me- References chanical ventilation continues to be a difficult task. Although potentially efficacious in selected IPF pa- 1. Hubbard R, Johnston I, Britton J. Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study. Chest 1998; 113: tients, NIV is associated with a relevant failure risk. 396-400. Subsequent transitioning to IMV does not, moreo- 2. Collard HR, Moore BB, Flaherty KR, et al. Idiopathic Pulmonary Fi- ver, substantially improve patients’ outcome, as the brosis Clinical Research Network Investigators. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2007; mortality rate in these patients is approximately 90% 176: 636-43. (7). 3. Agarwal R, Jindal SK. Acute exacerbation of idiopathic pulmonary fi- The case described here is, to our knowledge, brosis: a systematic review. Eur J Intern Med 2008; 19: 227-35. 4. Raghu G, Collard HR, Egan JJ, et al; ATS/ERS/JRS/ALAT Com- the first report concerning the utilization of an EC- mittee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/ CO2R device as an alternative to IMV in a patient JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based with acute worsening of IPF refractory to NIV sup- guidelines for diagnosis and management. Am J Respir Crit Care Med 2011; 183: 788-824. port: findings from preliminary experiences had con- 5. Yokoyama T, Kondoh Y, Taniguchi H, et al. Noninvasive ventilation in vinced us that this approach could prevent or reduce acute exacerbation of idiopathic pulmonary fibrosis. Intern Med 2010; the need for endotracheal intubation thus avoiding 49: 1509-14. 6. Vianello A, Arcaro G, Battistella L, et al. Noninvasive ventilation in problems linked to IMV. the event of acute respiratory failure in patients with idiopathic pulmo- Since a retrospective cohort study on adult pa- nary fibrosis. J Crit Care 2014; 29: 562-7. tients awaiting Lung Transplant (LT) found that 7. Mallick S. Outcome of patients with idiopathic pulmonary fibrosis (IPF) ventilated in intensive care unit. Respir Med 2008; 102: 1355-9. undergoing IMV before transplantation was an in- 8. Mani RK, Schmidt W, Lund LW, Herth FJ. Respiratory dialysis for 190 A. Vianello, G. Arcaro, L. Paladini, et al.
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10. Del Sorbo L, Pisani L, Filippini C, et al. Extracorporeal CO2 removal 15. Song JW, Hong SB, Lim CM, et al. Acute exacerbation of idiopathic in hypercapnic patients at risk of noninvasive ventilation failure: a pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J matched cohort study with historical control. Crit Care Med 2015; 2011; 37: 356-63. 43: 120-7. 16. Nava S, Rubini F. Lung and chest wall mechanics in ventilated pa- 11. Moscatelli A, Ottonello G, Nahum L, et al. Noninvasive ventilation tients with end stage idiopathic pulmonary fibrosis. Thorax 1999; 54: and low-flow veno-venous extracorporeal carbon dioxide removal as a 390-5. bridge to lung transplantation in a child with refractory hypercapnic 17. Vermeijden JW, Zijlstra JG, Erasmus ME, van der Bij W, Verschu- respiratory failure due to bronchiolitis obliterans. Pediatric Crit Care uren EA. Lung transplantation for ventilator-dependent respiratory Med 2010; 11: e8-12. failure. J Heart Lung Transplant 2009; 28: 347-51. 12. Kluge S, Braune SA, Engel M, et al. Avoiding invasive mechanical 18. Bein T, Weber F, Philipp A, et al. A new pumpless extracorporeal in- ventilation by extracorporeal carbon dioxide removal in patients fail- terventional lung assist in critical hypoxemia/hypercapnia. Crit Care ing noninvasive ventilation. Intensive Care Med 2012; 38: 1632-9. Med 2006; 34: 1372-7. 0235 - EXTRACORPOREAL CARBON DIOXIDE REMOVAL: A NEW LOW FLOW VENO-VENOUS DEVICE IN LUNG TRANSPLANTATION
B. Bergantino1, F. Ruberto1, F. Pugliese1, C. D'Arena1, P. Congi1, M. Frattini B1 1Policlinico Umberto I, UOD Terapia Intensiva e Trapianti d'Organo, Roma, Italy Lisbon 2012
Abstract
INTRODUCTION. Ventilation-refractory hypercapnia may frequently occur in patients undergoing lung transplantation, during the surgical procedure because of one lung ventilation, or in the post- operative period in case of primary lung dysfunction (PGD). When conventional therapies like ventilatory support, administration of inhaled nitric oxide (iNO) and intravenous prostacyclins are inadequate, additional extracorporeal gas exchange could be necessary to recover lung function. ProLung is a new veno-venous low-flow extracorporeal device to remove carbon dioxide in patients with respiratory acidosis. METHODS. On March and April 2012, a 27-year-old woman and a 28-year-old men underwent double sequential lung transplantation, both affected by cystic fibrosis. The first patient developed ventilation-refractory hypercapnia during the one lung ventilation in the operatory theatre; the men developed severe PGD in the postoperative period. The treatments already included ventilatory and hemodynamic support, iNO, and prostaglandine E1, but when partial pressure of CO2 reached values greater than 90mmHg with pH < 7,2 we started treatment with ProLung to remove CO2, using a central double lumen catheter. Hemodynamic and respiratory parameters were assessed at baseline and during the treatment. RESULTS. During the study we assisted to the hemodynamic parameters improvement with artery pressure increase, reduction in pulmonary and systemic resistances and progressive increase in cardiac index. pH values got gradually normal and partial pressure of CO2 reduced. At the same time ventilatory support was reduced, thereby mitigating biotrauma, barotraumas and the risk of volutrauma. In the case of PGD, the ProLung was useful for the weaning from mechanical ventilation, too. CONCLUSIONS. Pro-Lung didn't need a specialized staff and no adverse events occurred during the treatment. Thanks to its low invasivity and the absence of hemodynamic effects, in our initial experience, the use of ProLung may be an important aid for patients with mild hypoxia, but severe respiratory acidosis, in association with conventional therapy during the perioperative period in lung transplantation. Furthermore it could be an useful device for the earlier weaning from mechanical ventilation, reducing the serious risk of lung infection in lung transplanted patients.