Publications by authors named "Chitaru Kurihara"

60 Publications

Lung donation following SARS-CoV-2 infection.

Am J Transplant 2021 Jul 31. Epub 2021 Jul 31.

Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

There have been over 177 million cases of COVID-19 worldwide, many of whom could be organ donors. Concomitantly, there is an anticipated increase in the need for donor lungs due to expanding indications. Given that the respiratory tract is most commonly affected by COVID-19, there is an urgent need to develop donor assessment criteria while demonstrating safety and "efficacy" of lung donation following COVID-19 infection. Accordingly, we report an intentional transplant using lungs from a donor with recent, microbiologically confirmed, COVID-19 infection into a recipient suffering from COVID-19 induced ARDS and pulmonary fibrosis. In addition to the standard clinical assays, both donor and recipient lungs were analyzed using RNAscope, which confirmed that tissues were negative for SARS-CoV-2. Immunohistochemistry demonstrated colocalized KRT17+ basaloid-like epithelium and COL1A1+ fibroblasts, a marker suggestive of lung fibrosis in COVID-19 associated lung disease, in the explanted recipient lungs but absent in the donor lungs. We demonstrate that following a thorough assessment, lung donation following resolved COVID-19 infection is safe and feasible.
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http://dx.doi.org/10.1111/ajt.16777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441925PMC
July 2021

Modern ECMO circuitry may obviate the need for continuous systemic anticoagulation.

Ann Thorac Surg 2021 May 8. Epub 2021 May 8.

Northwestern University Feinberg School of Medicine, 676 N. St Clair St, Suite 650, Chicago, IL 60611. Electronic address:

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http://dx.doi.org/10.1016/j.athoracsur.2021.04.073DOI Listing
May 2021

Early outcomes after lung transplantation for severe COVID-19: a series of the first consecutive cases from four countries.

Lancet Respir Med 2021 05 31;9(5):487-497. Epub 2021 Mar 31.

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Background: Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications.

Methods: We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed.

Findings: Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19.

Interpretation: The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients.

Funding: National Institutes of Health. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/S2213-2600(21)00077-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012035PMC
May 2021

Crosstalk between nonclassical monocytes and alveolar macrophages mediates transplant ischemia-reperfusion injury through classical monocyte recruitment.

JCI Insight 2021 03 22;6(6). Epub 2021 Mar 22.

Division of Thoracic Surgery and.

Primary graft dysfunction (PGD) is the predominant cause of early graft loss following lung transplantation. We recently demonstrated that donor pulmonary intravascular nonclassical monocytes (NCM) initiate neutrophil recruitment. Simultaneously, host-origin classical monocytes (CM) permeabilize the vascular endothelium to allow neutrophil extravasation necessary for PGD. Here, we show that a CCL2-CCR2 axis is necessary for CM recruitment. Surprisingly, although intravital imaging and multichannel flow cytometry revealed that depletion of donor NCM abrogated CM recruitment, single cell RNA sequencing identified donor alveolar macrophages (AM) as predominant CCL2 secretors. Unbiased transcriptomic analysis of murine tissues combined with murine KOs and chimeras indicated that IL-1β production by donor NCM was responsible for the early activation of AM and CCL2 release. IL-1β production by NCM was NLRP3 inflammasome dependent and inhibited by treatment with a clinically approved sulphonylurea. Production of CCL2 in the donor AM occurred through IL-1R-dependent activation of the PKC and NF-κB pathway. Accordingly, we show that IL-1β-dependent paracrine interaction between donor NCM and AM leads to recruitment of recipient CM necessary for PGD. Since depletion of donor NCM, IL-1β, or IL-1R antagonism and inflammasome inhibition abrogated recruitment of CM and PGD and are feasible using FDA-approved compounds, our findings may have potential for clinical translation.
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http://dx.doi.org/10.1172/jci.insight.147282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026186PMC
March 2021

Prophylactic Ureaplasma-directed Antimicrobials in Lung Donors Can Prevent Fatal Hyperammonemia.

Transplantation 2021 03;105(3):e35-e36

Division of Thoracic Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.

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http://dx.doi.org/10.1097/TP.0000000000003540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905692PMC
March 2021

MELD Score Predicts Outcomes in Patients Undergoing Venovenous Extracorporeal Membrane Oxygenation.

ASAIO J 2021 08;67(8):871-877

From the Department of Medicine.

Venovenous extracorporeal membrane oxygenation (VV ECMO) is increasingly being used in the management of severe acute respiratory distress syndrome (ARDS). The Respiratory ECMO Survival Prediction (RESP) score is most commonly used to predict survival of patients undergoing ECMO. However, the RESP score does not incorporate renal and hepatic dysfunction which are frequently a part of the constellation of multiorgan dysfunction associated with ARDS. The Model for End-Stage Liver Disease (MELD) incorporates both liver and kidney dysfunction and is used in the risk stratification of liver transplant recipients as well as those undergoing cardiac surgery. The aim of this study was to assess the prognostic value of the MELD score in patients undergoing VV ECMO. Patients undergoing VV ECMO from 2016 to 2019 were extracted from our prospectively maintained institutional ECMO database and stratified based on MELD score. Baseline clinical, laboratory, and follow-up data, as well as post-ECMO outcomes, were compared. Of 71 patients, 50 patients (70.4%) had a MELD score <12 and 21 (29.6%) had a MELD score ≥12. The higher MELD score was associated with increased post-ECMO mortality but reduced risk of dialysis and tracheostomy. In multivariate analysis, higher MELD score (HR 1.35, 95% CI = 1.07-2.75), lower body surface area (HR 0.16, 0.04-0.65), RESP score (HR 0.75, 95% CI = 0.64-0.87), and platelet count (HR 0.99, 95% CI = 0.98-0.99), were significant predictors of postoperative mortality. We conclude that MELD score can be used complementarily to the RESP score to predict outcomes in patients with ARDS undergoing VV ECMO.
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http://dx.doi.org/10.1097/MAT.0000000000001321DOI Listing
August 2021

Lung transplantation for patients with severe COVID-19.

Sci Transl Med 2020 12 30;12(574). Epub 2020 Nov 30.

Division of Pulmonary and Critical Care Medicine, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Lung transplantation can potentially be a life-saving treatment for patients with nonresolving COVID-19-associated respiratory failure. Concerns limiting lung transplantation include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and the potential risk for allograft infection by pathogens causing ventilator-associated pneumonia in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to those of transplant. Here, we report the results of lung transplantation in three patients with nonresolving COVID-19-associated respiratory failure. We performed single-molecule fluorescence in situ hybridization (smFISH) to detect both positive and negative strands of SARS-CoV-2 RNA in explanted lung tissue from the three patients and in additional control lung tissue samples. We conducted extracellular matrix imaging and single-cell RNA sequencing on explanted lung tissue from the three patients who underwent transplantation and on warm postmortem lung biopsies from two patients who had died from COVID-19-associated pneumonia. Lungs from these five patients with prolonged COVID-19 disease were free of SARS-CoV-2 as detected by smFISH, but pathology showed extensive evidence of injury and fibrosis that resembled end-stage pulmonary fibrosis. Using machine learning, we compared single-cell RNA sequencing data from the lungs of patients with late-stage COVID-19 to that from the lungs of patients with pulmonary fibrosis and identified similarities in gene expression across cell lineages. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is their only option for survival.
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http://dx.doi.org/10.1126/scitranslmed.abe4282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050952PMC
December 2020

Lung transplantation for pulmonary fibrosis secondary to severe COVID-19.

medRxiv 2020 Oct 27. Epub 2020 Oct 27.

Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19 acute respiratory distress syndrome. Concerns limiting transplant include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and potential risk for allograft infection by pathogens associated with ventilator-induced pneumonia in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to transplant. Here, we report the results of the first two successful lung transplantation procedures in patients with non-resolving COVID-19 associated acute respiratory distress syndrome in the United States. We performed smFISH to detect both positive and negative strands of SARS-CoV-2 RNA in the explanted lung tissue, extracellular matrix imaging using SHIELD tissue clearance, and single cell RNA-Seq on explant and warm post-mortem lung biopsies from patients who died from severe COVID-19 pneumonia. Lungs from patients with prolonged COVID-19 were free of virus but pathology showed extensive evidence of injury and fibrosis which resembled end-stage pulmonary fibrosis. Single cell RNA-Seq of the explanted native lungs from transplant and paired warm post-mortem autopsies showed similarities between late SARS-CoV-2 acute respiratory distress syndrome and irreversible end-stage pulmonary fibrosis requiring lung transplantation. There was no recurrence of SARS-CoV-2 or pathogens associated with pre-transplant ventilator associated pneumonias following transplantation in either patient. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is the only option for survival.

Single Sentence Summary: Some patients with severe COVID-19 develop end-stage pulmonary fibrosis for which lung transplantation may be the only treatment.
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http://dx.doi.org/10.1101/2020.10.26.20218636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605582PMC
October 2020

Impact of Screening and Treatment of Ureaplasma spp on Hyperammonemia Syndrome in Lung Transplant Recipients: A Single Center Experience.

Clin Infect Dis 2020 Oct 17. Epub 2020 Oct 17.

Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Background: Infection with Ureaplasma species (spp) has been linked to fatal hyperammonemia syndrome (HS) in lung transplant recipients. We sought to characterize the epidemiology of Ureaplasma spp in candidates and donors and describe outcomes of antimicrobial therapy in preventing and treating HS.

Methods: Candidate testing for Ureaplasma spp was performed with urine culture and PCR pre-transplant. Positive candidates were treated with levofloxacin. Donor testing was performed with bronchoalveolar lavage culture and PCR intraoperatively. From 7/2014-2/2017 patients were treated according to results; from 2/2017-10/2018 recipients received empiric levofloxacin and azithromycin at transplant until testing returned negative. HS was defined as new onset altered mental status after transplant with ammonia > 200 µmol/L.

Results: 60 patients who underwent lung transplant were included. 80% (n = 48) of patients had negative screening tests in donor and candidate pre-lung transplant, 8.3% (n = 5) of recipients had positive Ureaplasma spp testing in urine pre-transplant, and 13.3% (n = 8) had positive donor BAL testing at the time of lung transplant. 3 patients developed HS a median of 7 days post-transplant; 2 died of HS. Recipients of organs with Ureaplasma spp who received empiric therapy did not develop HS. Donors with Ureaplasma spp were younger and more sexually active.

Conclusion: Donor-derived Ureaplasma spp in lung transplant was associated with HS. Screening lung donors for Ureaplasma spp might allow for targeted therapy to reduce risk for development of HS, but future confirmatory studies are needed.
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http://dx.doi.org/10.1093/cid/ciaa1570DOI Listing
October 2020

Residual endotoxin induces primary graft dysfunction through ischemia/reperfusion-primed alveolar macrophages.

J Clin Invest 2020 08;130(8):4456-4469

Division of Thoracic Surgery.

Despite the widespread use of antibiotics, bacterial pneumonias in donors strongly predispose to the fatal syndrome of primary graft dysfunction (PGD) following lung transplantation. We report that bacterial endotoxin persists in human donor lungs after pathogen is cleared with antibiotics and is associated with neutrophil infiltration and PGD. In mouse models, depletion of tissue-resident alveolar macrophages (TRAMs) attenuated neutrophil recruitment in response to endotoxin as shown by compartmental staining and intravital imaging. Bone marrow chimeric mice revealed that neutrophils were recruited by TRAM through activation of TLR4 in a MyD88-dependent manner. Intriguingly, low levels of endotoxin, insufficient to cause donor lung injury, promoted TRAM-dependent production of CXCL2, increased neutrophil recruitment, and led to PGD, which was independent of donor NCMs. Reactive oxygen species (ROS) increased in human donor lungs starting from the warm-ischemia phase and were associated with increased transcription and translocation to the plasma membrane of TLR4 in donor TRAMs. Consistently, scavenging ROS or inhibiting their production to prevent TLR4 transcription/translocation or blockade of TLR4 or coreceptor CD14 on donor TRAMs prevented neutrophil recruitment in response to endotoxin and ameliorated PGD. Our studies demonstrate that residual endotoxin after successful treatment of donor bacterial pneumonia promotes PGD through ischemia/reperfusion-primed donor TRAMs.
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http://dx.doi.org/10.1172/JCI135838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410086PMC
August 2020

Comparative effectiveness and cost-efficiency of surgical approaches for thymectomy.

Surgery 2020 10 5;168(4):737-742. Epub 2020 Jul 5.

Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL; Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Electronic address:

Background: We compared the clinical outcomes and cost-efficiency of surgical approaches (sternotomy-open, video assisted thoracoscopic surgery, and robotic assisted thoracic surgery) for thymectomy.

Methods: This is a retrospective review of 220 consecutive patients who underwent thymectomy between January 1, 2007, and January 31, 2017. Surgical approach was determined by the surgeon, but we only included cases that could be resected using any of the 3 approaches.

Results: Open approach was used in 69 patients, whereas minimally invasive technique was used in 151 (97, video assisted thoracoscopic surgery; 54, robotic assisted thoracic surgery). Open surgery was associated with greater total hospital cost ($22,847 ± $20,061 vs $14,504 ± $10,845, P < .001). Open group also revealed longer duration of intensive care unit (1.2 ± 2.8 vs 0.2 ± 1.3 days, P < .001) and hospital stay (4.3 ± 4.0 vs 2.0 ± 2.6 days, P < .001). There were no differences in major adverse clinical outcomes. Long-term recurrence-free survival after resection of thymoma was similar between the groups.

Conclusion: Minimally invasive techniques were equally efficacious compared with the open approach in the resection of the thymus. Additionally, their use was associated with decreased hospital duration of stay and reduced cost. Hence the use of minimally invasive approaches should be encouraged in the resection of thymus.
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http://dx.doi.org/10.1016/j.surg.2020.04.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816338PMC
October 2020

Pre-Intubation Veno-Venous Extracorporeal Membrane Oxygenation in Patients at Risk for Respiratory Decompensation.

J Extra Corpor Technol 2020 Mar;52(1):52-57

Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has emerged as a potential life-saving treatment for patients with acute respiratory failure. Given the accumulating literature supporting the use of VV-ECMO without therapeutic levels of anticoagulation, it might be feasible to use it for planned intubation before surgical procedures. Here, we report consecutive series of patients who underwent planned initiation of VV-ECMO, without anticoagulation, before induction of general anesthesia for anticipated difficult airways or respiratory decompensation. We describe the approach to safely initiate VV-ECMO in an awake patient. We retrospectively identified patients in a prospectively maintained database who underwent planned initiation of VV-ECMO before intubation. Standard statistical methods were used to determine post-procedure outcomes. Patients included were three men and one woman, with a mean age of 34.3 ± 10.4 years. Indications included mediastinal lymphoma, foreign body obstruction, hemoptysis, and tracheo-esophageal fistula. VV-ECMO was initiated electively for all patients, and no anticoagulation was used. The median duration of VV-ECMO support was 2.5 days (1-11 days), the median length of ventilator dependence and intensive care unit stay was 1 day (1-23 days) and 5 days (4-31 days), respectively. The median length of stay was 18.5 days (8-39 days). There were no thrombotic complications and no mortality at 30 days. Initiation of awake VV-ECMO is feasible and is safe before intubation and induction of anesthesia in patients at high risk for respiratory decompensation.
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http://dx.doi.org/10.1182/JECT-1900035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138124PMC
March 2020

Feasibility of Venovenous Extracorporeal Membrane Oxygenation Without Systemic Anticoagulation.

Ann Thorac Surg 2020 10 12;110(4):1209-1215. Epub 2020 Mar 12.

Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address:

Background: Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly being used for acute respiratory distress syndrome and as a bridge to lung transplantation. After initiation of venovenous ECMO, systemic anticoagulation therapy is traditionally administered and can cause bleeding diathesis. Here, we investigated whether venovenous ECMO can be administered without continuous systemic anticoagulation administration for patients with acute respiratory distress syndrome.

Methods: This is a retrospective review of an institutional ECMO database. We included consecutive patients from January 2015 through February 2019. Overall, 38 patients received low levels of continuous systemic anticoagulation (AC+) whereas the subsequent 36 patients received standard venous thromboprophylaxis (AC-). Published Extracorporeal Life Support Organization guidelines were used for the definition of outcomes and complications.

Results: Overall, survival was not different between the two groups (P = .58). However, patients in the AC+ group had higher rates of gastrointestinal bleeding (28.9%, vs AC- group 5.6%; P < .001). The events per patient-day of gastrointestinal bleeding was 0.00025 in the AC- group and 0.00064 in the AC+ group (P < .001). In addition, oxygenator dysfunction was increased in the AC+ group (28.9% and 0.00067 events per patient-day, vs AC- 11.1% and 0.00062 events per patient-day; P = .02). Furthermore, the AC+ group received more transfusions: packed red blood cells, AC+ group 94.7% vs AC- group 55.5% (P < .001); fresh frozen plasma, AC+ 60.5% vs AC- 16.6% (P = .001); and platelets, AC+ 84.2% vs AC- 27.7% (P < .001). There was no circuit thrombosis in either groups throughout the duration of ECMO support.

Conclusions: Our results suggest that venovenous ECMO can be safely administered without continuous systemic anticoagulation therapy. This approach may be associated with reduced bleeding diathesis and need for blood transfusions.
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http://dx.doi.org/10.1016/j.athoracsur.2020.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486253PMC
October 2020

Sternum-Sparing HVAD Implantation with Attachment of the Outflow Graft to the Descending Aorta.

ASAIO J 2020 Sep/Oct;66(9):1006-1013

From the Division of Cardiothoracic Transplant and Assist Devices, Baylor College of Medicine, Houston, Texas.

The standard approach for implanting an HVAD left ventricular assist device (LVAD) is performing a median sternotomy and sewing the outflow graft to the ascending aorta. However, in patients with sternal comorbidities, it may be advantageous to use a sternum-sparing approach. We retrospectively studied eight patients who underwent HVAD implantation for destination therapy via a left subcostal or fifth/sixth intercostal space incision. With this procedure, the outflow graft was sewed to the descending aorta. Ninety-day and one-year survival rates were 87.5% and 75%, respectively. Two patients (25%) died during the perioperative period: one from multisystem organ failure and the other from unrelated causes. We adjusted the HVAD speed to open the aortic valve once every three to four beats. Compared with other continuous-flow LVAD implantations performed at our institution during the study period (n = 437), this technique resulted in shorter bypass times and a lower incidence of infection; it was not associated with an increased incidence of heart failure, aortic root thrombosis, pump thrombosis, progression of aortic insufficiency, or ischemic neurologic dysfunction. Our findings suggest that a sternum-sparing approach for HVAD implantation is feasible and may be a safe option in patients with serious comorbidities that preclude the use of traditional implantation techniques.
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http://dx.doi.org/10.1097/MAT.0000000000001136DOI Listing
March 2021

Thoracoscopic lung biopsy under regional anesthesia for interstitial lung disease.

Reg Anesth Pain Med 2020 04 16;45(4):255-259. Epub 2020 Feb 16.

Department of Surgery, Division of Thoracic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Background: Interstitial lung disease (ILD) management guidelines support lung biopsy-guided therapy. However, the high mortality associated with thoracoscopic lung biopsy using general anesthesia (GA) in patients with ILD has deterred physicians from offering this procedure and adopt a diagnostic approach based on high-resolution CT. Here we report that thoracoscopy under regional anesthesia could be a safer alternative for lung biopsy and effectively guide ILD treatment.

Methods: This was a single-center retrospective review of prospectively maintained database and consisted of patients who underwent thoracoscopic lung biopsy between March 2016 and March 2018. Patients were divided into two groups: (A) GA, and (B) regional anesthesia using monitored anesthesia care (MAC) and thoracic epidural anesthesia (TEA).

Results: During the study period, 44 patients underwent thoracoscopic lung biopsy. Of these, 15 underwent MAC/TEA. There were no significant differences between the two groups with regard to pulmonary function test and clinicodemographic profile. However, operative time and hospital stay were shorter in MAC/TEA group (32.5±18.5 min vs 50.8±18.4; p=0.004, 1.0±1.3 days vs 10.0±34.7 days; p<0.001, respectively). Eight patients in the GA group, but none in the MAC/TEA group, experienced worsening of ILD after lung biopsy (p=0.03). Additionally, one patient in the GA group died due to acute ILD worsening. No cases of MAC/TEA group had to be converted to GA. In all cases a pathological diagnosis could be made.

Conclusions: Thoracoscopy using regional anesthesia might be a safer alternative to lung biopsy in patients with ILD.
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http://dx.doi.org/10.1136/rapm-2019-100686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362779PMC
April 2020

Outcomes in patients who underwent a concomitant tricuspid valve procedure during left ventricular assist device implantation.

J Card Surg 2019 Dec 15;34(12):1458-1464. Epub 2019 Nov 15.

Division of Cardiothoracic Transplant and Assist Devices, Baylor College of Medicine, Houston, Texas.

Background: Study findings have been inconsistent regarding whether a concomitant tricuspid valve replacement or repair performed concurrently with continuous-flow left ventricular assist device (CF-LVAD) implantation has additive clinical benefit in patients with severe tricuspid valve regurgitation (TR).

Aim Of Study: To determine the effect of performing a concomitant tricuspid valve procedure (TVP) at the time of CF-LVAD implantation on patient outcomes.

Methods: We retrospectively reviewed our single-institution experience in 526 patients who underwent primary implantation of a CF-LVAD between November 2003 and March 2016. We identified 59 (11.2%) patients who had severe TR at the time of implantation and analyzed the effect of performing a concomitant TVP at the time of CF-LVAD implantation on the rate of survival, incidence of postoperative right heart failure (RHF), recurrence of TR, and incidence of 30-day readmission.

Results: We did not observe a significant difference in the overall survival rate (P = .51), incidence of postoperative RHF (P = .26), or recurrence of TR (P = .73) between patients with severe TR who underwent a TVP and those who did not at the time of CF-LVAD implantation. However, the incidence of 30-day readmission was significantly lower in patients who underwent a TVP than in those who did not (P = .002).

Conclusions: Performing a concomitant TVP at the time of CF-LVAD implantation did not improve patient outcomes but reduced the incidence of 30-day readmission.
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http://dx.doi.org/10.1111/jocs.14304DOI Listing
December 2019

Effect of cardiac arrest with aortic cross-clamping during left ventricular assist device implantation.

Interact Cardiovasc Thorac Surg 2020 01;30(1):47-53

Division of Cardiothoracic Transplantation and Circulatory Support, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.

Objectives: Some patients who undergo continuous-flow left ventricular assist device (CF-LVAD) implantation require concomitant procedures that can be performed with or without cardiac arrest under aortic cross-clamping (AXC). Procedures normally performed with cardiac arrest are sometimes avoided or performed without cardiac arrest because it may be detrimental to right heart function. However, the effects of cardiac arrest on patients with advanced heart failure necessitating CF-LVAD support have not been thoroughly studied. We examined our single-centre experience to determine whether cardiac arrest during CF-LVAD implantation was associated with worse patient outcomes.

Methods: From November 2003 to March 2016, a total of 526 patients with chronic end-stage heart failure underwent primary CF-LVAD implantation. Preoperative demographics, postoperative complications and mortality rates were compared between patients who required cardiac arrest with AXC (n = 50) and those who did not (n = 476).

Results: The most frequently performed procedure requiring AXC was aortic valve closure (n = 23, 26.1%). Although the AXC group had longer cardiopulmonary bypass times (P < 0.01), long-term (5-year) survival was similar in AXC and non-AXC patients (P = 0.13). Also, postoperative right heart failure (P = 0.15) and neurological dysfunction (P = 0.89) rates were not significantly different between the 2 groups. Cox proportional hazards analysis showed that cardiac arrest with AXC was not an independent predictor of mortality (hazard ratio, 0.89; P = 0.73).

Conclusions: Cardiac arrest with AXC during CF-LVAD implantation did not negatively affect long-term survival or the incidence of right ventricular failure or stroke. These findings should be considered in deciding surgical strategies. Additional investigation may be warranted to further understand the effects of cardiac arrest during LVAD implantation.
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http://dx.doi.org/10.1093/icvts/ivz223DOI Listing
January 2020

Reply.

Ann Thorac Surg 2020 03 14;109(3):988. Epub 2019 Sep 14.

Division of Cardiothoracic Transplantation and Circulatory Support, Baylor College of Medicine, Houston, Texas.

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http://dx.doi.org/10.1016/j.athoracsur.2019.07.088DOI Listing
March 2020

Device exchange from Heartmate II to HeartWare HVAD.

J Card Surg 2019 Nov 3;34(11):1204-1207. Epub 2019 Sep 3.

Division of Cardiothoracic Transplant and Mechanical Circulatory Support, Baylor College of Medicine, Houston, Texas.

Background: Despite technological advancements, pump durability and pump-related complications continue to affect and adversely impact the lives of patients with end-stage heart failure on left ventricular assist device (LVAD) support. In an attempt to avoid recurrent LVAD-related complications, there may be circumstances where it is clinically advantageous to exchange a patient's device from HeartMate II to HeartWare HVAD. However, there is a paucity of data that describes the safety and feasibility of such an approach.

Objective: We present the largest single-center series of HeartMate II (HMII) to HeartWare (HVAD) device exchanges.

Methods: A retrospective review of 11 patients who underwent HMII to HVAD exchange from 2012 to 2017 was conducted to evaluate patient characteristics, incidence of postoperative complications, and survival.

Results: Eleven male patients (mean age 55 ± 14.4 years) underwent HMII to HVAD device exchange. One patient expired on postoperative day 7 secondary to sepsis. One patient was lost-to-follow-up after 23 months. An additional three patients died at 5, 7, and 24 months. Mean follow-up after device exchange was 1555 ± 311 days for the remaining six patients. None of the 11 study patients underwent LVAD explant, further device exchange, or heart transplant.

Conclusion: Exchange of an HMII LVAD to an HVAD can be performed safely with acceptable perioperative morbidity and mortality.
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http://dx.doi.org/10.1111/jocs.14229DOI Listing
November 2019

Gastrointestinal Bleeding After HeartMate II or HVAD Implantation: Incidence, Location, Etiology, and Effect on Survival.

ASAIO J 2020 03;66(3):283-290

From the Division of Cardiothoracic Transplantation and Circulatory Support, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas.

The number of patients on destination therapy is increasing as long-term survival on continuous-flow left ventricular assist device (CF-LVAD) therapy has improved. Gastrointestinal bleeding (GIB) is a common complication after CF-LVAD implantation, and its risk correlates with longer support time, emphasizing the importance of GIB management. The lower pulsatility of CF-LVADs may promote arteriovenous malformations, which amplify the bleeding risk. Here, we retrospectively analyzed the location, incidence, and survival effect of GIB events in HeartMate II (HM-II) and HeartWare Ventricular Assist Device (HVAD) recipients to provide specific details regarding these complications. From November 2003 to March 2016, 526 patients with chronic heart failure underwent primary implantation of an HM-II (n = 403) or HVAD (n = 123) CF-LVAD at our center. Of the 526 patients, 140 (26.6%) had a GIB event (HM-II: n = 100; HVAD: n = 40), 92 (17.5%) had a single GIB event, and 48 (9.1%) had multiple GIB events (range: 2-9 events). HVAD recipients had a higher incidence of both upper and lower GIB events (p < 0.001 and P = 0.002, respectively) than HM-II recipients. Arteriovenous malformation was the most common etiology for GIB (50 patients/72 events); for this group, the average time-to-event was 300.4 days, the recurrence rate was 34%, and the 90-day and 1-year survival rates were 88.3% and 66.7%, respectively. Age at implantation was the only predictor of GIB. In conclusion, our study provides detailed information about GIB events associated with current CF-LVADs. Additional studies are required to evaluate strategies to reduce the incidence of GIB morbidity.
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http://dx.doi.org/10.1097/MAT.0000000000000998DOI Listing
March 2020

Concomitant valve procedures in patients undergoing continuous-flow left ventricular assist device implantation: A single-center experience.

J Thorac Cardiovasc Surg 2019 10 21;158(4):1083-1089.e1. Epub 2019 Feb 21.

Division of Cardiothoracic Transplant and Assist Devices, Baylor College of Medicine, Houston, Tex.

Objective: Long-term support with continuous-flow left ventricular assist devices (CF-LVADs) has improved the outcomes of patients with end-stage heart failure. However, valve disease management in patients who undergo CF-LVAD implantation remains controversial. The aim of this study was to assess our single-center experience with patients who underwent a concomitant valve procedure during implantation of a CF-LVAD.

Methods: From November 2003 through March 2016, 526 patients underwent primary CF-LVAD implantation with a HeartMate II (St Jude Inc, St Paul, Minn; n = 403) or HeartWare (Medtronic, Minneapolis, Minn; n = 123) device at our center. Of those, 91 underwent a concomitant valve procedure during implantation (CF-LVAD+valve procedure group), whereas 435 did not (CF-LVAD-only group). We compared preoperative characteristics and short-term and mid-term survival rates between these groups.

Results: The concomitant valve procedures performed included 13 tricuspid valve repairs, 19 aortic valve repairs or replacements, 30 mitral valve repairs or replacements, and 29 double valve repairs or replacements. Survival rates at 1 month, 6 months, 12 months, and 24 months were 90.3%, 81.4%, 74.9%, and 67.4%, respectively, for the CF-LVAD-only group and 89.0%, 75.8%, 70.3%, and 65.9%, respectively, for the CF-LVAD+valve procedure group (P = .55). The results of Cox regression multivariable modeling showed that performing a concomitant valve procedure was not an independent predictor of mortality (hazard ratio, 1.29; 95% confidence interval, 0.96-1.74; P = .08).

Conclusions: In our experience, performing a concomitant valve procedure during CF-LVAD implantation was not associated with an increased mortality rate. The decision to perform a concomitant valve procedure should be made primarily on the basis of clinical indications for the procedure.
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http://dx.doi.org/10.1016/j.jtcvs.2019.02.040DOI Listing
October 2019

A left ventricular end-diastolic dimension less than 6.0 cm is associated with mortality after implantation of an axial-flow pump.

J Thorac Cardiovasc Surg 2019 06 21;157(6):2302-2310. Epub 2019 Jan 21.

Division of Cardiothoracic Transplantation and Circulatory Support, Baylor College of Medicine, Houston, Tex.

Objective: The effects of having a lower left ventricular end-diastolic dimension before HeartMate II (Thoratec Corp, Pleasanton, Calif) left ventricular assist device implantation remain unclear. We analyzed our single-center data on HeartMate II implantation to determine whether having a lower left ventricular end-diastolic dimension preoperatively was associated with inferior outcomes.

Methods: From November 2003 to March 2016, 393 patients with chronic heart failure underwent primary HeartMate II implantation. We compared the preoperative left ventricular end-diastolic dimension and associated survival outcomes of these patients to determine the left ventricular end-diastolic dimension cutoff for worse overall survival. Then, we compared the preoperative demographics, stroke rate, and mortality of patients with a left ventricular end-diastolic dimension above the cutoff for worse survival with those of patients with a left ventricular end-diastolic dimension below the cutoff.

Results: A Cox multivariate regression model showed that low left ventricular end-diastolic dimension was an independent predictor of mortality (hazard ratio, 1.49; P = .02). The Contal and O'Quigley method showed that overall survival postimplantation was decreased in patients with a left ventricular end-diastolic dimension less than 6.0 cm (n = 91). Kaplan-Meier analysis confirmed that the left ventricular end-diastolic dimension less than 6.0 cm group had lower overall survival than the left ventricular end-diastolic dimension 6.0 cm or greater group (P = .04). Furthermore, a competing-risk analysis showed that postoperative stroke was more common in the left ventricular end-diastolic dimension less than 6.0 cm group than in the left ventricular end-diastolic dimension 6.0 cm or greater group (P < .01).

Conclusions: Overall survival was decreased and postoperative stroke was increased in HeartMate II recipients with a preoperative left ventricular end-diastolic dimension less than 6.0 cm. Future research should determine the left ventricular end-diastolic dimension cutoff values for safely implanting other support devices, and device designs should be improved to better accommodate the needs of patients with a limited left ventricle size.
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http://dx.doi.org/10.1016/j.jtcvs.2019.01.015DOI Listing
June 2019

Severe LVAD-related infections requiring surgical treatment: Incidence, predictors, effect on survival, and impact of device selection.

J Card Surg 2019 Feb 2;34(2):82-91. Epub 2019 Feb 2.

Division of Cardiothoracic Transplant and Assist Devices, Baylor College of Medicine, Houston, Texas.

Background: Left ventricular assist devices (LVADs) are being used more frequently for treating refractory, advanced heart failure. However, infection remains a frequent complication. In this study, we analyzed the incidence of severe infections in LVAD recipients to determine its impact on survival.

Methods: From May 2009 through March 2016, 437 patients with advanced heart failure underwent implantation of a continuous-flow LVAD (n = 314, HeartMate II LVAD [Abbott Laboratories, Abbott Park, IL]; n = 123 HeartWare HVAD [Medtronic, Minneapolis, MN]). We analyzed the rate of severe device infection requiring surgical intervention or involving sepsis and the impact of severe infection on outcomes in patients on long-term LVAD support.

Results: Infection occurred in 244 patients (HeartMate II, n = 186; HVAD, n = 58); severe infections developed in 160 patients (HeartMate II, n = 119; HVAD, n = 41). HeartMate II recipients had 344 severe infection events (0.63 events per patient-year [EPPY]), whereas HeartWare recipients had 89 severe infection events (0.42 EPPY; P = 0.047). HeartMate II recipients had a higher incidence of pump infections (P < 0.001). Severe infections did not significantly affect survival (P = 0.42).

Conclusions: Although HeartMate II patients had a significantly higher incidence of pump infections requiring surgical treatment, survival was not adversely affected. The difference in postoperative infection rates may be an important factor in device type selection.
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http://dx.doi.org/10.1111/jocs.13987DOI Listing
February 2019

Use of ProtekDuo as Veno-arterial and Veno-venous Extracorporeal Membrane Oxygenation During Bilateral Lung Transplantation.

J Cardiothorac Vasc Anesth 2019 Aug 22;33(8):2250-2254. Epub 2018 Dec 22.

Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL.

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http://dx.doi.org/10.1053/j.jvca.2018.12.025DOI Listing
August 2019

Long-Term Impact of Cytomegalovirus Serologic Status on Lung Transplantation in the United States.

Ann Thorac Surg 2019 04 23;107(4):1046-1052. Epub 2018 Nov 23.

Division of Thoracic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Pulmonary & Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address:

Background: Cytomegalovirus (CMV) infection has been associated with poor outcomes after solid organ transplantation. The long-term impact of donor and recipient CMV serological status on lung transplant outcomes remains unclear. Accordingly, we evaluated the impact of donor and recipient CMV status on long-term patients as well as allograft survival after single (SLT) and double lung transplantation (BLT).

Methods: The Scientific Registry of Transplant Recipients was used to track all adult lung transplants in United States from May 2005 to June 2016. Patient mortality and bronchiolitis obliterans syndrome were determined up to 5 years using Cox proportional hazards modeling. Additionally, landmark analysis was performed conditional on survival at 1 year.

Results: Compared with donor negative-recipient CMV-IgG negative (D-R-), donor positive-recipient negative (D+R-) and donor positive-recipient positive (D+R+) groups had increased mortality at 1 and 5 years after BLT, with the former demonstrating highest risk. Although mortality was not increased with CMV seropositive donors after SLT at 1 year, both D+R- and D+R+ groups demonstrated greater mortality at 5 years. Risk of bronchiolitis obliterans syndrome was not affected by CMV serological status. Conditional landmark analysis confirmed that lungs from CMV seropositive donors conferred highest risk for long-term mortality.

Conclusions: CMV seronegative recipients undergoing either BLT or SLT from CMV seropositive donors have the highest risk of long-term mortality that extends beyond the first year. Further studies are needed to determine the causes of higher mortality observed in the CMV seronegative recipients and risks and benefits of extension of CMV prophylaxis, particularly in the high-risk group.
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http://dx.doi.org/10.1016/j.athoracsur.2018.10.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844363PMC
April 2019

Fatal Neurologic Dysfunction During Continuous-Flow Left Ventricular Assist Device Support.

Ann Thorac Surg 2019 04 20;107(4):1132-1138. Epub 2018 Nov 20.

Division of Cardiothoracic Transplantation and Circulatory Support, Baylor College of Medicine, Houston, Texas.

Background: During continuous-flow left ventricular assist device (CF-LVAD) support, neurologic dysfunction (ND) is a common complication and can be fatal. Few reports provide detailed data on neurologic mortality in such patients. Therefore, we examined ND-related mortality during CF-LVAD support.

Methods: Between November 2003 and March 2016, 526 patients underwent implantation of a CF-LVAD (403 HeartMate II [Thoratec, Pleasanton, CA] and 123 HVAD [HeartWare International, Framingham, MA]) at our center. We categorized ND as hemorrhagic or ischemic and recorded resulting deaths. Records were reviewed to determine preoperative demographics, perioperative variables, prevalence and causes of postimplantation ND, duration of support until ND, time from ND to death, laboratory data and medications at the time of ND, post-ND treatment procedures, and causes of hemorrhagic ND. We also performed Cox multivariable logistic regression analysis to identify predictors of ND-related mortality by calculating odds ratios and confidence intervals.

Results: Neurologic dysfunction occurred in 141 patients (26.8%), 48 (9.1%) of whom subsequently died. Median duration of left ventricular assist device support before ND was 230 days (range, 3 to 2,422), and median time from ND to death was 3.5 days (range, 0 to 55). Parenchymal hemorrhage was the most frequent cause of early conversion (76.7%). In the Cox multivariable regression analysis, predictors of fatal ND were age, ischemic cause of heart failure, history of stroke, and longer intraoperative aortic cross-clamp time.

Conclusions: Our study elucidates the characteristics and risk factors of patients who died of ND during CF-LVAD support. Further studies are required to find ways to decrease the incidence of fatal ND during CF-LVAD support.
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http://dx.doi.org/10.1016/j.athoracsur.2018.10.012DOI Listing
April 2019

Effect of concomitant mitral valve procedures for severe mitral regurgitation during left ventricular assist device implantation.

J Artif Organs 2019 Jun 25;22(2):91-97. Epub 2018 Oct 25.

Division of Cardiothoracic Transplantation and Circulatory Support, Baylor College of Medicine, Houston, TX, USA.

The effect of performing a concomitant mitral valve procedure (MVP) during continuous-flow left ventricular assist device (CF-LVAD) implantation has been reported for patients with moderate-to-severe mitral regurgitation (MR), but moderate MR is less of a clinical concern for CF-LVAD patients. There is a paucity of reports focusing on patients with severe MR. Thus, the purpose of this study was to analyze the effect of performing a concomitant MVP during CF-LVAD implantation in patients with severe preoperative MR. Between November 2003 and March 2016, 526 patients underwent primary implantation of a CF-LVAD at our center. Patients with severe MR who underwent a concomitant MVP were compared to those who did not in regard to overall survival, perioperative complications, postoperative echocardiography data, bridge-to-transplantation success, and CF-LVAD explantation. Of the 108 patients with severe MR, 26 underwent a concomitant MVP and 82 did not. These groups showed no difference in survival (p = 0.61). Additionally, the two groups had similar rates of postoperative right heart failure (p = 0.69) and readmissions (p = 0.42). The 24-month follow-up echocardiography results were also similar. Furthermore, the groups showed no difference in bridge-to-cardiac transplantation success (30.0% vs 25.0%, p = 0.80) or CF-LVAD explantation rates (0.0% vs 0.0%. p = 1.0). Our findings suggest that patients with severe MR who undergo a MVP during CF-LVAD implantation do not have superior outcomes to those who do not. However, assessments of other outcomes may show some benefits to performing concomitant MVPs.
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http://dx.doi.org/10.1007/s10047-018-1076-8DOI Listing
June 2019

Left Ventricular Recovery with Explantation of Continuous-Flow Left Ventricular Assist Device after 5 Years of Support.

Ann Thorac Cardiovasc Surg 2021 Jun 28;27(3):211-214. Epub 2018 Aug 28.

Division of Cardiothoracic Transplant and Assist Devices, Baylor College of Medicine, Houston, TX, USA.

Mechanical circulatory support may result in sufficient myocardial recovery to allow for explantation of the left ventricular assist device (LVAD). The duration of support associated with left ventricular recovery has generally been 6-12 months. In this report, we present a patient in whom the left ventricle recovered after 5 years of support with a LVAD. Our report demonstrates that long-term monitoring for left ventricular recovery is prudent and may allow for late device explantation.
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http://dx.doi.org/10.5761/atcs.cr.18-00082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343026PMC
June 2021

Continuous-Flow Left Ventricular Assist Device Therapy in Adults with Transposition of the Great Vessels.

Ann Thorac Cardiovasc Surg 2021 Feb 10;27(1):64-67. Epub 2018 Aug 10.

Division of Cardiothoracic Transplantation and Circulatory Support, Baylor College of Medicine, Houston Texas, USA.

An increasing number of children with congenital heart disease are surviving into adulthood and subsequently developing end-stage heart failure. Two example populations are adults who have been previously operated on for congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA). Implantation of a continuous flow left ventricular assist device (CF-LVAD) in these patients can present unusual anatomical and physiologic challenges. In this report, we describe outcomes of CF-LVAD implantation in three such patients. These cases demonstrate the feasibility of implanting a CF-LVAD in patients who have undergone surgery for CCTGA and/or TGA.
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http://dx.doi.org/10.5761/atcs.cr.18-00021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043028PMC
February 2021

Extracorporeal Membrane Oxygenation Can Successfully Support Patients With Severe Acute Respiratory Distress Syndrome in Lieu of Mechanical Ventilation.

Crit Care Med 2018 11;46(11):e1070-e1073

Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.

Objectives: Extracorporeal membrane oxygenation is increasingly used in the management of severe acute respiratory distress syndrome. With extracorporeal membrane oxygenation, select patients with acute respiratory distress syndrome can be managed without mechanical ventilation, sedation, or neuromuscular blockade. Published experience with this approach, specifically with attention to a patient's respiratory drive following cannulation, is limited.

Design: We describe our experience with three consecutive patients with severe acute respiratory distress syndrome supported with right jugular-femoral configuration of venovenous extracorporeal membrane oxygenation without therapeutic anticoagulation as an alternative to lung-protective mechanical ventilation. Outcomes are reported including daily respiratory rate, vital capacities, and follow-up pulmonary function testing.

Results: Following cannulation, patients were extubated within 24 hours. During extracorporeal membrane oxygenation support, all patients were able to maintain a normal respiratory rate and experienced steady improvements in vital capacities. Patients received oral nutrition and ambulated daily. At follow-up, no patients required supplemental oxygen.

Conclusions: Our results suggest that venovenous extracorporeal membrane oxygenation can provide a safe and effective alternative to lung-protective mechanical ventilation in carefully selected patients. This approach facilitates participation in physical therapy and avoids complications associated with mechanical ventilation.
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http://dx.doi.org/10.1097/CCM.0000000000003354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185806PMC
November 2018
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