Original Cardiovascular
Extracorporeal Life Support in “Awake” Patients as a Bridge to Lung Transplant Prashant N. Mohite1 Anton Sabashnikov1 Anna Reed1 Diana G. Saez1 Nikhil P. Patil1 Aron-Frederik Popov1 Fabio DeRobertis1 Toufan Bahrami1 Mohamed Amrani1 Martin Carby1 Sundip Kaul1 Andre R. Simon1
Support, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom Thorac Cardiovasc Surg
Abstract
Keywords
► awake ECMO ► extracorporeal membrane oxygenator ► lung transplant
Background Traditionally, patients on extracorporeal membrane oxygenation (ECMO) are sedated and mechanically ventilated, which increases risk of complications related to immobility and mechanical ventilation. The purpose of this study was to assess the feasibility and highlight the benefits of a bridge to lung transplant (LTx) using “awake ECMO” support. Methods The peripheral venovenous or venoarterial ECMO was implanted at a bedside. A retrospective study of patients undergoing LTx between January 2007 and March 2013 was performed. Outcomes in patients supported on ECMO as a bridge to LTx and kept “awake” (Group 1) were compared with the rest of the LTx patients (Group 2). Results In this period, 249 LTx were performed and in them 7 patients were bridged to LTx using “awake ECMO” strategy. Two patients were awake at ECMO implantation and throughout the therapy, and two patients were on ventilator support at the time of ECMO implantation who were extubated later and maintained awake until LTx. The remaining three patients were awake for some time during the ECMO. There was no statistically significant difference in most donor characteristics and recipient baseline characteristics as well as post-LTx parameters between the two groups. One-year survival estimate was not different between the groups: Group 1, 85.7% vs. Group 2, 86.3% (log rank p ¼ 0.99). Conclusion In end-stage lung disease, the ECMO can be commenced in “awake” patients and patients can be awakened on ECMO. The “awake ECMO” strategy may avoid complications related to mechanical ventilation, sedation, and immobilization and provide comparable outcomes in the high-risk LTx patients.
Introduction Patients with end-stage lung disease have limited respiratory reserve. Infection or exacerbation may compromise these reserves and the patient may need ventilator assistance. Noninvasive ventilation is a first-line treatment; however, it
received November 17, 2014 accepted after revision December 10, 2014
Address for correspondence Prashant N. Mohite, MCh, Department of Cardiothoracic Transplantation and Mechanical Support, Harefield Hospital, Royal Brompton and Harefield NHS Foundation Trust, Middlesex, London UB9 6JH, United Kingdom (e-mail: [email protected]).
is temporary, not very effective, and usually not tolerated for long periods of time. Invasive ventilation with endotracheal intubation followed by tracheotomy in prolonged cases of respiratory failure becomes mandatory to bridge such patients to LTx. In conventional management, extracorporeal membrane oxygenation (ECMO) remains a last resort in the
© Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0035-1546429. ISSN 0171-6425.
Downloaded by: University of British Columbia. Copyrighted material.
1 Department of Cardiothoracic Transplantation and Mechanical
Mohite et al.
treatment of end-stage lung disease. Traditionally, ECMO patients are heavily sedated to prevent inadvertent cannula dislodgement and to avoid respiratory compromise which make mechanical ventilation mandatory. This in turn leads to an increased risk of complications associated with immobility, prolonged ventilation, and enteral feeding. Series of patients with end-stage lung disease treated with ECMO while remaining awake are recently published.1,2 In an attempt to evaluate the effect of “awake” ECMO as a bridge to LTx, we retrospectively collected the recipient and the donor characteristics, as well as outcomes of LTx, for all the LTx performed at our center over a 7-year period and compared the “awake” ECMO-bridged recipients with the rest of the patients who were transplanted electively.
Patients and Methods The Institutional Review Board at our center approved this study and waived the need for individual patient consent. The study design was a retrospective single center study with the prospectively collected data. A total of 249 LTx were performed at Harefield Hospital between January 2007 and March 2013. Recipients were divided into two groups: patients supported on ECMO as a bridge to LTx and kept “awake” (Group 1 ¼ 7) and the rest of the elective LTx patients (Group 2 ¼ 242). The parameters of early and midterm outcome were compared: pO2/FiO2 ratio at the end of the transplant; 24, 48, and 72 hours after transplant; duration of mechanical ventilation; intensive care unit (ICU); and total hospital stay; as well as need for postoperative use of ECMO, overall survival, and freedom from bronchiolitis obliterans syndrome (BOS).
Organ Assessment and Organ Procurement Protocol The decision to accept the organ was based on donor medical history, CXR review, arterial blood gas, bronchoscopy, and surgical evaluation during retrieval. Ante-retrograde pulmonary artery/pulmonary veins flush technique with low potassium dextran (Perfadex, Medisan, Uppsala, Sweden) solution augmented with CaCl2, 3.6% tromethamine (THAM, Hospira Inc, Lake Forest, Illinois, United States), and epoprostenol sodium 2.5 mL/L was used for organ protection. The total ischemic time was defined as the time between cardiac arrest in donors after cardiac death (DCD) donors or aortic cross clamp in DBD (donation after brain death) donors and reperfusion of the second implanted lung. Detailed donor data, such as demographic parameters, cause of death, current clinical status, laboratory investigations, and past social and medical history were analyzed. Demographics and perioperative recipient data as well as midterm outcome were compared. BOS was diagnosed when posttransplant fraction of expired volume in 1 second (FEV1) measured on a regularly basis after the transplant permanently dropped to >20% of the best FEV1 achieved after LTx.
Extracorporeal Membrane Oxygenation Equipment We used Levitronix (Thoratec, Pleasanton, California, United States) pump head and Medos Hilite (Inspiration Healthcare Ltd., Leicester, United Kingdom) 7000LToxygenator as a standard Thoracic and Cardiovascular Surgeon
set for ECMO. Venovenous ECMO was established via Avalon Elite bi-caval dual lumen catheter (Maquet, Rastatt, Germany) inserted through right internal jugular vein. Venoarterial ECMO was implanted via groin vessels; cannulation was performed with a BioMedicus (Medtronic, Inc. Minneapolis, Minnesota, United States) femoral cannula.
Anticoagulation The activated clotting time (ACT) was done before insertion of cannulas, and 100 IU/kg body weight of unfractionated of Heparin was given. The procedure was performed when ACT reached 200 seconds. The additional bolus of heparin was given if this level of ACT was not achieved. Once the ECMO started functioning, the anticoagulation was maintained by continuous intravenous infusion of unfractionated heparin started initially at a low dose and later titrated aiming activated partial prothrombin time between 60 and 80 seconds or ACT between 160 and 180 seconds.
Maintenance of Extracorporeal Membrane Oxygenation and Patient Care The flows were monitored by flow meters applied over postoxygenator tubing which were displayed continuously on the Levitronix monitor. It also displayed pre- and postoxygenator pressures (P1 and P2) which gave idea about the pressure gradient across the oxygenator. We also used real-time monitoring of hematocrit, mixed venous blood saturation with continuous display. The perfusionist team surveyed the patient once a day; performed pre- and postoxygenator blood gas analyses to ensure proper functioning of oxygenator; and did necessary cannula, connection, and monitor checks. Whenever patient was awake at the time of insertion of ECMO, the insertion of cannulas was facilitated by local anesthesia and mild sedation. Once patients were intubated, they were given every opportunity to wake up by weaning the sedation and ventilator. Later on, they were maintained in “awake” status throughout the entire ECMO therapy. Patients on ECMO could eat, drink, interact with family, and were subjected to intensive physiotherapy.
Statistical Analysis Data were obtained from cardiothoracic donor information forms and recipient chart review. Statistical analysis was performed using IBM SPSS Statistics, version 21 software (IBM Corp., Chicago, Illinois, United States). The data are presented as continuous or categorical variables. Continuous data were evaluated for normality using one sample Kolmogorov-Smirnov test, and are expressed as the mean standard deviation (SD) in cases of normal distributed or median (interquartile range) in cases of non–normal distributed variables. Categorical data are expressed as total numbers and percentages. Intergroup comparisons were performed using either one way ANOVA or Kruskal–Wallis test for normal and nonnormal continuous variables, respectively. Pearson χ2 or Fisher exact tests were used for categorical data dependent on the minimum expected count in each cross tab. A p-value
Extracorporeal Life Support in “Awake” Patients as a Bridge to Lung Transplant Prashant N. Mohite1 Anton Sabashnikov1 Anna Reed1 Diana G. Saez1 Nikhil P. Patil1 Aron-Frederik Popov1 Fabio DeRobertis1 Toufan Bahrami1 Mohamed Amrani1 Martin Carby1 Sundip Kaul1 Andre R. Simon1
Support, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom Thorac Cardiovasc Surg
Abstract
Keywords
► awake ECMO ► extracorporeal membrane oxygenator ► lung transplant
Background Traditionally, patients on extracorporeal membrane oxygenation (ECMO) are sedated and mechanically ventilated, which increases risk of complications related to immobility and mechanical ventilation. The purpose of this study was to assess the feasibility and highlight the benefits of a bridge to lung transplant (LTx) using “awake ECMO” support. Methods The peripheral venovenous or venoarterial ECMO was implanted at a bedside. A retrospective study of patients undergoing LTx between January 2007 and March 2013 was performed. Outcomes in patients supported on ECMO as a bridge to LTx and kept “awake” (Group 1) were compared with the rest of the LTx patients (Group 2). Results In this period, 249 LTx were performed and in them 7 patients were bridged to LTx using “awake ECMO” strategy. Two patients were awake at ECMO implantation and throughout the therapy, and two patients were on ventilator support at the time of ECMO implantation who were extubated later and maintained awake until LTx. The remaining three patients were awake for some time during the ECMO. There was no statistically significant difference in most donor characteristics and recipient baseline characteristics as well as post-LTx parameters between the two groups. One-year survival estimate was not different between the groups: Group 1, 85.7% vs. Group 2, 86.3% (log rank p ¼ 0.99). Conclusion In end-stage lung disease, the ECMO can be commenced in “awake” patients and patients can be awakened on ECMO. The “awake ECMO” strategy may avoid complications related to mechanical ventilation, sedation, and immobilization and provide comparable outcomes in the high-risk LTx patients.
Introduction Patients with end-stage lung disease have limited respiratory reserve. Infection or exacerbation may compromise these reserves and the patient may need ventilator assistance. Noninvasive ventilation is a first-line treatment; however, it
received November 17, 2014 accepted after revision December 10, 2014
Address for correspondence Prashant N. Mohite, MCh, Department of Cardiothoracic Transplantation and Mechanical Support, Harefield Hospital, Royal Brompton and Harefield NHS Foundation Trust, Middlesex, London UB9 6JH, United Kingdom (e-mail: [email protected]).
is temporary, not very effective, and usually not tolerated for long periods of time. Invasive ventilation with endotracheal intubation followed by tracheotomy in prolonged cases of respiratory failure becomes mandatory to bridge such patients to LTx. In conventional management, extracorporeal membrane oxygenation (ECMO) remains a last resort in the
© Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0035-1546429. ISSN 0171-6425.
Downloaded by: University of British Columbia. Copyrighted material.
1 Department of Cardiothoracic Transplantation and Mechanical
Mohite et al.
treatment of end-stage lung disease. Traditionally, ECMO patients are heavily sedated to prevent inadvertent cannula dislodgement and to avoid respiratory compromise which make mechanical ventilation mandatory. This in turn leads to an increased risk of complications associated with immobility, prolonged ventilation, and enteral feeding. Series of patients with end-stage lung disease treated with ECMO while remaining awake are recently published.1,2 In an attempt to evaluate the effect of “awake” ECMO as a bridge to LTx, we retrospectively collected the recipient and the donor characteristics, as well as outcomes of LTx, for all the LTx performed at our center over a 7-year period and compared the “awake” ECMO-bridged recipients with the rest of the patients who were transplanted electively.
Patients and Methods The Institutional Review Board at our center approved this study and waived the need for individual patient consent. The study design was a retrospective single center study with the prospectively collected data. A total of 249 LTx were performed at Harefield Hospital between January 2007 and March 2013. Recipients were divided into two groups: patients supported on ECMO as a bridge to LTx and kept “awake” (Group 1 ¼ 7) and the rest of the elective LTx patients (Group 2 ¼ 242). The parameters of early and midterm outcome were compared: pO2/FiO2 ratio at the end of the transplant; 24, 48, and 72 hours after transplant; duration of mechanical ventilation; intensive care unit (ICU); and total hospital stay; as well as need for postoperative use of ECMO, overall survival, and freedom from bronchiolitis obliterans syndrome (BOS).
Organ Assessment and Organ Procurement Protocol The decision to accept the organ was based on donor medical history, CXR review, arterial blood gas, bronchoscopy, and surgical evaluation during retrieval. Ante-retrograde pulmonary artery/pulmonary veins flush technique with low potassium dextran (Perfadex, Medisan, Uppsala, Sweden) solution augmented with CaCl2, 3.6% tromethamine (THAM, Hospira Inc, Lake Forest, Illinois, United States), and epoprostenol sodium 2.5 mL/L was used for organ protection. The total ischemic time was defined as the time between cardiac arrest in donors after cardiac death (DCD) donors or aortic cross clamp in DBD (donation after brain death) donors and reperfusion of the second implanted lung. Detailed donor data, such as demographic parameters, cause of death, current clinical status, laboratory investigations, and past social and medical history were analyzed. Demographics and perioperative recipient data as well as midterm outcome were compared. BOS was diagnosed when posttransplant fraction of expired volume in 1 second (FEV1) measured on a regularly basis after the transplant permanently dropped to >20% of the best FEV1 achieved after LTx.
Extracorporeal Membrane Oxygenation Equipment We used Levitronix (Thoratec, Pleasanton, California, United States) pump head and Medos Hilite (Inspiration Healthcare Ltd., Leicester, United Kingdom) 7000LToxygenator as a standard Thoracic and Cardiovascular Surgeon
set for ECMO. Venovenous ECMO was established via Avalon Elite bi-caval dual lumen catheter (Maquet, Rastatt, Germany) inserted through right internal jugular vein. Venoarterial ECMO was implanted via groin vessels; cannulation was performed with a BioMedicus (Medtronic, Inc. Minneapolis, Minnesota, United States) femoral cannula.
Anticoagulation The activated clotting time (ACT) was done before insertion of cannulas, and 100 IU/kg body weight of unfractionated of Heparin was given. The procedure was performed when ACT reached 200 seconds. The additional bolus of heparin was given if this level of ACT was not achieved. Once the ECMO started functioning, the anticoagulation was maintained by continuous intravenous infusion of unfractionated heparin started initially at a low dose and later titrated aiming activated partial prothrombin time between 60 and 80 seconds or ACT between 160 and 180 seconds.
Maintenance of Extracorporeal Membrane Oxygenation and Patient Care The flows were monitored by flow meters applied over postoxygenator tubing which were displayed continuously on the Levitronix monitor. It also displayed pre- and postoxygenator pressures (P1 and P2) which gave idea about the pressure gradient across the oxygenator. We also used real-time monitoring of hematocrit, mixed venous blood saturation with continuous display. The perfusionist team surveyed the patient once a day; performed pre- and postoxygenator blood gas analyses to ensure proper functioning of oxygenator; and did necessary cannula, connection, and monitor checks. Whenever patient was awake at the time of insertion of ECMO, the insertion of cannulas was facilitated by local anesthesia and mild sedation. Once patients were intubated, they were given every opportunity to wake up by weaning the sedation and ventilator. Later on, they were maintained in “awake” status throughout the entire ECMO therapy. Patients on ECMO could eat, drink, interact with family, and were subjected to intensive physiotherapy.
Statistical Analysis Data were obtained from cardiothoracic donor information forms and recipient chart review. Statistical analysis was performed using IBM SPSS Statistics, version 21 software (IBM Corp., Chicago, Illinois, United States). The data are presented as continuous or categorical variables. Continuous data were evaluated for normality using one sample Kolmogorov-Smirnov test, and are expressed as the mean standard deviation (SD) in cases of normal distributed or median (interquartile range) in cases of non–normal distributed variables. Categorical data are expressed as total numbers and percentages. Intergroup comparisons were performed using either one way ANOVA or Kruskal–Wallis test for normal and nonnormal continuous variables, respectively. Pearson χ2 or Fisher exact tests were used for categorical data dependent on the minimum expected count in each cross tab. A p-value
