Publications by authors named "Robert H Bartlett"

191 Publications

ECMO for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization (ELSO).

ASAIO J 2021 Feb 26. Epub 2021 Feb 26.

Department of Emergency Medicine, University of Washington, USA Division of Pulmonary Critical Care and Sleep Medicine, University of Washington, USA General ICU, University Hospital of Parma, Italy Department of Biomedical, Metabolic and Neural Sciences, University of Modena & Reggio Emilia, Italy Extracorporeal Life Support Organization Texas Children's Hospital, Baylor College of Medicine Children's Medical Center of Dallas, University of Texas Southwestern Medical Center Extracorporeal Life Support Organization, President; Children's Healthcare of Atlanta, Emory University Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, USA University of Michigan Department of Critical Care, Guy's and St. Thomas' NHS Foundation Trust Centre for Human & Applied Physiological Sciences, Faculty of Life Sciences & Medicine, King's College London Sorbonne Université, INSERM, Institute of Cardiometabolism and Nutrition Service de médecine intensive-réanimation, Institut de Cardiologie, APHP Sorbonne Université Hôpital Pitié-Salpêtrière, F-75013 PARIS, France Department of Cardio-Thoracic Surgery - Maastricht University Medical Centre - Cardiovascular Research Institute Maastricht Maastricht, The Netherlands Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany Nemours Children's Health System Congenital Heart Center, Departments of Surgery and Pediatrics, University of Florida, Gainesville, USA Intensive Care Unit, Alfred Health Melbourne, Victoria, Australia Critical Care ECMO service, King Saud Medical City - Ministry Of Health (MOH), Riyadh - Saudi Arabia. Fundación Cardiovascular de Colombia Service de Médecine Intensive-Réanimation, Institut de Cardiologie, AP-HP, Sorbonne Université Hôpital Pitié-Salpêtrière, Paris, France. Sorbonne Université, GRC n°30, GRC RESPIRE, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Paris, France. Adult Intensive Care Services, The Prince Charles Hospital, Brisbane, Queensland, Australia National University Hospital, Singapore Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, USA.

This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19-related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19-related ARDS, myocarditis or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001422DOI Listing
February 2021

Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest (EROCA): Results of a Randomized Feasibility Trial of Expedited Out-of-Hospital Transport.

Ann Emerg Med 2021 Feb 1. Epub 2021 Feb 1.

Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI; Michigan Center for Integrative Research in Critical Care, University of Michigan Medical School, Ann Arbor, MI; Extracorporeal Life Support Laboratory, University of Michigan Medical School, Ann Arbor, MI.

Study Objective: Outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest depend on time to therapy initiation. We hypothesize that it would be feasible to select refractory out-of-hospital cardiac arrest patients for expedited transport based on real-time estimates of the 911 call to the emergency department (ED) arrival interval, and for emergency physicians to rapidly initiate ECPR in eligible patients.

Methods: In a 2-tiered emergency medical service with an ECPR-capable primary destination hospital, adults with refractory shockable or witnessed out-of-hospital cardiac arrest were randomized 4:1 to expedited transport or standard care if the predicted 911 call to ED arrival interval was less than or equal to 30 minutes. The primary outcomes were the proportion of subjects with 911 call to ED arrival less than or equal to 30 minutes and ED arrival to ECPR flow less than or equal to 30 minutes.

Results: Of 151 out-of-hospital cardiac arrest 911 calls, 15 subjects (10%) were enrolled. Five of 12 subjects randomized to expedited transport had an ED arrival time of less than or equal to 30 minutes (overall mean 32.5 minutes [SD 7.1]), and 5 were eligible for and treated with ECPR. Three of 5 ECPR-treated subjects had flow initiated in less than or equal to 30 minutes of ED arrival (overall mean 32.4 minutes [SD 10.9]). No subject in either group survived with a good neurologic outcome.

Conclusion: The Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest trial did not meet predefined feasibility outcomes for selecting out-of-hospital cardiac arrest patients for expedited transport and initiating ECPR in the ED. Additional research is needed to improve the accuracy of predicting the 911 call to ED arrival interval, optimize patient selection, and reduce the ED arrival to ECPR flow interval.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.annemergmed.2020.11.011DOI Listing
February 2021

Membrane Lung and Blood Pump Use During Prolonged Extracorporeal Membrane Oxygenation: Trends From 2002 to 2017.

ASAIO J 2021 Jan 28. Epub 2021 Jan 28.

From the Extracorporeal Life Support Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI Department of Pediatrics, Division of Critical Care. University of Michigan, Ann Arbor, MI Registry Committee, Extracorporeal Life Support Organization, Ann Arbor, MI Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI Technology Committee, Extracorporeal Life Support Organization, Ann Arbor, MI.

Extracorporeal life support (ECLS) has grown in its application since its first clinical description in the 1970s. The technology has been used to support a wide variety of mechanical support modalities and diseases, including respiratory failure, cardiorespiratory failure, and cardiac failure. Over many decades and safety and efficacy studies, followed by randomized clinical trials and thousands of clinical uses, ECLS is considered as an accepted treatment option for severe pulmonary and selected cardiovascular failure. Extracorporeal life support involves the use of support artificial organs, including a membrane lung and blood pump. Over time, changes in the technology and the management of ECLS support devices have evolved. This manuscript describes the use of membrane lungs and blood pumps used during ECLS support from 2002 to 2017 in over 65,000 patients reported to the Extracorporeal Life Support Organization Registry. Device longevity and complications associated with membrane lungs and blood pump are described and stratified by age group: neonates, pediatrics, and adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001368DOI Listing
January 2021

Prolonged (≥ 24 hours) Normothermic (≥ 32 °C) Ex Vivo Organ Perfusion: Lessons From the Literature.

Transplantation 2020 Oct 7. Epub 2020 Oct 7.

University of Michigan, Department of Surgery, Ann Arbor, MI, USA.

For two centuries, researchers have studied ex vivo perfusion intending to preserve the physiologic function of isolated organs. If it were indeed possible to maintain ex vivo organ viability for days, transplantation could become an elective operation with clinicians methodically surveilling and reconditioning allografts before surgery. To this day, experimental reports of successfully prolonged (≥ 24 hours) organ perfusion are rare and have not translated into clinical practice. In order to identify the crucial factors necessary for successful perfusion, this review summarizes the history of prolonged normothermic ex vivo organ perfusion. By examining successful techniques and protocols used, this review outlines the essential elements of successful perfusion, limitations of current perfusion systems, and areas where further research in preservation science is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003475DOI Listing
October 2020

Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry.

Lancet 2020 10 25;396(10257):1071-1078. Epub 2020 Sep 25.

Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, and Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, NY, USA.

Background: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date.

Methods: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality.

Findings: Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4-40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20-2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6-41·5).

Interpretation: In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19.

Funding: None.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(20)32008-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518880PMC
October 2020

Enhanced Hemocompatibility and Analytical Accuracy of Intravascular Potentiometric Carbon Dioxide Sensors via Nitric Oxide Release.

Anal Chem 2020 10 29;92(20):13641-13646. Epub 2020 Sep 29.

Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.

In this letter, the innate ability of nitric oxide (NO) to inhibit platelet activation/adhesion/thrombus formation is employed to improve the hemocompatibility and accuracy of an intravascular (IV) potentiometric CO (partial pressure of carbon dioxide) sensor. The catheter-type sensor is fabricated by impregnating a segment of dual lumen silicone tubing with a proton ionophore, plasticizer, and lipophilic cation-exchanger. Subsequent filling of bicarbonate and strong buffer solutions and placement of Ag/AgCl reference electrode wires within each lumen, respectively, enables measurement of the membrane potential difference across the inner wall of the tube, with this potential changing as a function of the logarithm of sample CO. The dual lumen device is further encapsulated within a -nitroso--acetyl-DL-penicillamine (SNAP)-doped silicone tube that releases physiological levels of NO. The NO releasing sensor exhibits near-Nernstian sensitivity toward CO (slope = 59.31 ± 0.78 mV/decade) and low drift rates (<2 mV/24 h after initial equilibration). evaluation of the NO releasing sensors, performed in the arteries and veins of anesthetized pigs for 20 h, shows enhanced accuracy (vs non-NO releasing sensors) when benchmarked to measurements of discrete blood samples made with a commercial blood gas analyzer. The accurate, continuous monitoring of blood CO levels achieved with this new IV NO releasing CO sensor configuration could help better manage hospitalized patients in critical care units.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.0c02979DOI Listing
October 2020

Physiology of Extracorporeal Gas Exchange.

Compr Physiol 2020 07 8;10(3):879-891. Epub 2020 Jul 8.

University of Michigan, Ann Arbor, Michigan, USA.

Circulating venous blood outside the body, through an artificial lung (membrane oxygenator), and returning oxygenated blood to the patient is extracorporeal gas exchange. Oxygen and carbon dioxide exchange in a membrane lung is controlled by regulating blood flow, blood composition, and device design. With this control, lung function can be replaced for weeks by artificial organs. © 2020 American Physiological Society. Compr Physiol 10:879-891, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cphy.c190006DOI Listing
July 2020

Choice of ECMO as a Therapy in COVID-19?

ASAIO J 2020 08;66(8):e112

Division of Pediatric Critical Care, Emory University, Atlanta, Georgia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001235DOI Listing
August 2020

Prolonged Organ Perfusion.

ASAIO J 2020 07;66(7):e100

Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, Michigan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001103DOI Listing
July 2020

Extracorporeal Membrane Oxygenation for Respiratory Failure.

Anesthesiology 2020 05;132(5):1257-1276

From the Department of Anesthesiology and Intensive Care Medicine, University of Göttingen Medical Center, Göttingen, Germany (M.Q., M.B., L.G.) University of Michigan, Ann Arbor, Michigan (R.H.B.) Perioperative Medicine and Critical Care Research Group, Southampton NIHR Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, United Kingdom (M.P.W.G.) Sorbonne Université, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Paris, France (A.C.) Service of Intensive Care, Institute of Cardiology, APHP Hôpital Pitié-Salpêtrière, Paris, France (A.C.) Alma Mater Studiorum - Department of Medical and Surgical Sciences, University of Bologna, Anesthesia and Intensive Care Medicine, Policlinico di Sant'Orsola, Bologna, Italy (M.V.R., M.B.) Department of Clinical, Integrated, and Experimental Medicine (DIMES), Respiratory and Critical Care, Sant'Orsola Malpighi Hospital, Bologna, Italy (S.N.) Department of Medicine, Columbia University College of Physicians and Surgeons, and New York Presbyterian Medical Center, New York, New York (D.B.) Department of Adult Critical Care, Guy's and St. Thomas' NHS Foundation Trust, King's Health Partners, and Division of Centre of Human Applied Physiological Sciences, King's College London, London, United Kingdom (L.C., F.V.) Department of Pulmonary and Critical Care Medicine, Regions Hospital and University of Minnesota, Minneapolis/St. Paul, Minnesota (J.J.M.).

This review focuses on the use of veno-venous extracorporeal membrane oxygenation for respiratory failure across all blood flow ranges. Starting with a short overview of historical development, aspects of the physiology of gas exchange (i.e., oxygenation and decarboxylation) during extracorporeal circulation are discussed. The mechanisms of phenomena such as recirculation and shunt playing an important role in daily clinical practice are explained.Treatment of refractory and symptomatic hypoxemic respiratory failure (e.g., acute respiratory distress syndrome [ARDS]) currently represents the main indication for high-flow veno-venous-extracorporeal membrane oxygenation. On the other hand, lower-flow extracorporeal carbon dioxide removal might potentially help to avoid or attenuate ventilator-induced lung injury by allowing reduction of the energy load (i.e., driving pressure, mechanical power) transmitted to the lungs during mechanical ventilation or spontaneous ventilation. In the latter context, extracorporeal carbon dioxide removal plays an emerging role in the treatment of chronic obstructive pulmonary disease patients during acute exacerbations. Both applications of extracorporeal lung support raise important ethical considerations, such as likelihood of ultimate futility and end-of-life decision-making. The review concludes with a brief overview of potential technical developments and persistent challenges.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ALN.0000000000003221DOI Listing
May 2020

Tidal Flow Perfusion for the Artificial Placenta: A Paradigm Shift.

ASAIO J 2020 07;66(7):796-802

From the Department of Surgery, ECLS Laboratory, University of Michigan, Ann Arbor, Michigan.

The modalities of vascular access for the extracorporeal artificial placenta (AP) have undergone many iterations over the past decade. We hypothesized that single lumen cannulation (SLC) of the jugular vein using tidal flow extracorporeal life (ECLS) support is a feasible alternative to venovenous (VV) umbilical-jugular cannulation and double lumen cannulation (DLC) and can maintain fetal circulation, stable hemodynamics, and adequate gas exchange for 24 hours. After in vitro evaluation of the tidal flow system, six preterm lambs at estimated gestational age 118-124 days (term 145 days) were delivered and underwent VV-ECLS. Three were supported using DLC and three with SLC utilizing tidal flow AP support. Hemodynamics, circuit flow, and gas exchange were monitored. Target fetal parameters were as follows: mean arterial pressure 40-60 mmHg, heart rate 140-240 beats per minute (bpm), SatO2% 60-80%, PaO2 25-50 mmHg, PaCO2 30-55 mmHg, oxygen delivery >5 ml O2/dl/kg/min, and circuit flow 100 ± 25 ml/kg/min. All animals survived 24 hours and maintained fetal circulation with stable hemodynamics and adequate gas exchange. Parameters of the tidal flow group were comparable with those of DLC. Single lumen jugular cannulation using tidal flow is a promising vascular access strategy for AP support. Successful miniaturization holds great potential for clinical translation to support extremely premature infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103518PMC
July 2020

Predicting Survival of Adult Respiratory Failure Patients Receiving Prolonged (≥14 Days) Extracorporeal Membrane Oxygenation.

ASAIO J 2020 07;66(7):825-833

From the Division of Acute Care Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.

Extracorporeal membrane oxygenation (ECMO) for adult respiratory failure has significantly increased, with longer duration ECMO support required in severe hypoxemia. We sought to examine independent predictors of survival of adult respiratory failure patients requiring prolonged (≥14 days) ECMO. We reviewed Extracorporeal Life Support Organization Registry data on all adult (≥18 years) patients who required P- ECMO (n = 4,361) over 10 years (2009-2018). Hospital survival was 51.3%, increased from 45.4% in our prior report of 974 patients (1989-2013). Univariate analysis confirmed factors associated with decreased mortality: younger age, white race, increased body weight, viral/bacterial pneumonia, higher positive end expiratory pressure, neuromuscular blockade, VV-ECMO mode, and decreased time from intubation to ECMO. For Pre-ECLS support, most vasopressor/inotropic drugs and nitric oxide had no association with mortality, but steroids (22% vs. 15%, p < 0.001), epinephrine (15% vs. 12%, p = 0.039), and bicarbonate (9% vs. 7%, p = 0.049) were more common in non-survivors. Extracorporeal membrane oxygenation complications (gastrointestinal hemorrhage, neurologic complications, and CPR) were associated with increased mortality. The RESP score was higher in survivors (-0.31 ± 3.36 vs. -0.83 ± 3.34, P < 0.001); however, discrimination was poor (c-statistic = 0.540 ± 0.009); it did not remain in the final model. A multivariable prediction model based on all information at ECMO initiation was fair (c-statistic = 0.670 + 0.012), but discrimination improved with the addition of ECMO complications (c-statistic = 0.675 + 0.012). These findings suggest that reducing ECMO-related complications will improve survival. We have identified predictors of mortality in prolonged ECMO patients, and inclusion of ECMO complications in a new predictive model improved discrimination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001067DOI Listing
July 2020

Ex Vivo Heart Perfusion for 72 Hours Using Plasma Cross Circulation.

ASAIO J 2020 07;66(7):753-759

Department of Pediatric Cardiology, Mott Children's Hospital, Ann Arbor, Michigan.

Preservation of a donor heart for transplantation is limited to 6-8 hours. Based on our demonstration of 12 hour perfusion with plasma cross circulation, this study aimed to evaluate ex vivo heart perfusion (EVHP) for up to 72 hours using cross plasma circulation (XC-plasma) from a live, awake paracorporeal sheep (PCS). Six ovine hearts were perfused for 72 hours using plasma cross circulation at a rate of 1 L/min with a live, awake PCS. Controls were seven perfused hearts without cross circulation. Experiments were electively ended at 72 hours, and epinephrine (0.1 mg) was delivered to demonstrate hormonal responsiveness. All controls failed at 6-10 hours. All six hearts perfused for 72 hours maintained normal heart function, metabolism, and responsiveness to epinephrine. Blood gases, electrolytes, and lactate levels were normal and stable throughout the study. All hearts appeared suitable for transplantation. We have demonstrated successful normothermic EVHP for 72 hours.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001061DOI Listing
July 2020

Nitric Oxide Attenuates the Inflammatory Effects of Air During Extracorporeal Circulation.

ASAIO J 2020 07;66(7):818-824

From the Department of Surgery, University of Michigan, Ann Arbor, Michigan.

Cardiopulmonary bypass causes a systemic inflammatory response reaction that may contribute to postoperative complications. One cause relates to the air/blood interface from the extracorporeal circuit. The modulatory effects of blending nitric oxide (NO) gas into the ventilation/sweep gas of the membrane lung was studied in a porcine model of air-induced inflammation in which NO gas was added and compared with controls with or without an air/blood interface. Healthy swine were supported on partial bypass under four different test conditions. Group 1: no air exposure, group 2: air alone, group 3: air plus 50 ppm NO, and group 4: air plus 500 ppm NO. The NO gas was blended into the ventilation/sweep site of the membrane lung. The platelets and leucocytes were activated by air alone. Addition of NO to the sweep gas attenuated the inflammatory response created by the air/blood interface in this model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024006PMC
July 2020

A Model of Pediatric End-Stage Lung Failure in Small Lambs <20 kg.

ASAIO J 2020 05;66(5):572-579

From the Extracorporeal Life Support Laboratory, Department of Surgery.

One in five children with end-stage lung failure (ESLF) die while awaiting lung transplant. No suitable animal model of ESLF exists for the development of artificial lung devices for bridging to transplant. Small lambs weighing 15.7 ± 3.1 kg (n = 5) underwent ligation of the left anterior pulmonary artery (PA) branch, and gradual occlusion of the right main PA over 48 hours. All animals remained hemodynamically stable. Over seven days of disease model conditions, they developed pulmonary hypertension (mean PA pressure 20 ± 5 vs. 33 ± 4 mm Hg), decreased perfusion (SvO2 66 ± 3 vs. 55 ± 8%) with supplemental oxygen requirement, and severe tachypneic response (45 ± 9 vs. 82 ± 23 breaths/min) (all p < 0.05). Severe right heart dysfunction developed (tricuspid annular plane systolic excursion 13 ± 3 vs. 7 ± 2 mm, fractional area change 36 ± 6 vs. 22 ± 10 mm, ejection fraction 51 ± 9 vs. 27 ± 17%, all p < 0.05) with severe tricuspid regurgitation and balloon-shaped dilation of the right ventricle. This model of pediatric ESLF reliably produces pulmonary hypertension, right heart strain, and impaired gas exchange, and will be used to develop a pediatric artificial lung.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851459PMC
May 2020

Long-term Effects of Hypothermic Ex Situ Perfusion on Skeletal Muscle Metabolism, Structure, and Force Generation After Transplantation.

Transplantation 2019 10;103(10):2105-2112

Department of Orthopaedic Surgery, University of Michigan Health System, Ann Arbor, MI.

Background: Hypothermic ex situ perfusion (HESP) systems are used to prolong allograft survival in solid organ transplantations and have been shown to be superior to static cold storage (SCS) methods. However, the effect of this preservation method on limb allograft survival and long-term function has not yet been tested. In this study, we investigated the long-term effects of the HESP on skeletal muscle metabolism, structure, and force generation and compared it with the current standard of preservation.

Methods: Forty male Lewis rats (250 ± 25 g) were divided into 5 groups, including naive control, sciatic nerve transection or repair, immediate transplantation, SCS, and HESP. For the SCS group, limbs were preserved at 4°C for 6 hours. In the HESP group, limbs were continuously perfused with oxygenated histidine-tryptophan-ketoglutarate (HTK) solution at 10-15°C for 6 hours. Hemodynamic and biochemical parameters of perfusion were recorded throughout the experiment. At 12 weeks, electromyography and muscle force measurements (maximum twitch and tetanic forces) were obtained along with muscle samples for histology and metabolomics analysis.

Results: Histology demonstrated 48% myocyte injury in the HESP group compared with 49% in immediate transplantation (P = 0.96) and 74% in the SCS groups (P < 0.05). The maximum twitch force measurement revealed a significantly higher force in the HESP group compared with the SCS group (P = 0.029). Essential amino acid levels of the gastrocnemius muscle did not reach significance, with the exception of higher proline levels in the HESP group.

Conclusions: HESP using HTK protects viability of the limb but fails to restore muscle force in the long term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000002800DOI Listing
October 2019

Low-Resistance, Concentric-Gated Pediatric Artificial Lung for End-Stage Lung Failure.

ASAIO J 2020 04;66(4):423-432

From the Extracorporeal Life Support Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan.

Children with end-stage lung failure awaiting lung transplant would benefit from improvements in artificial lung technology allowing for wearable pulmonary support as a bridge-to-transplant therapy. In this work, we designed, fabricated, and tested the Pediatric MLung-a dual-inlet hollow fiber artificial lung based on concentric gating, which has a rated flow of 1 L/min, and a pressure drop of 25 mm Hg at rated flow. This device and future iterations of the current design are designed to relieve pulmonary arterial hypertension, provide pulmonary support, reduce ventilator-associated injury, and allow for more effective therapy of patients with end-stage lung disease, including bridge-to-transplant treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293821PMC
April 2020

International Survey on Extracorporeal Membrane Oxygenation Transport.

ASAIO J 2020 02;66(2):214-225

Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles, ULB, Brussels, Belgium.

Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy for severe respiratory and circulatory failure. It is best performed in high-volume centers to optimize resource utilization and outcomes. Regionalization of ECMO might require the implementation of therapy before and during transfer to the high-volume center. The aim of this international survey was to describe the manner in which interhospital ECMO transport care is organized at experienced centers. Fifteen mobile ECMO centers from nine countries participated in this survey. Seven (47%) of them operated under the "Hub-and-Spoke" model. Transport team composition varies from three to nine members, with at least one ECMO specialist (i.e., nurse or perfusionist) participating in all centers, although intensivists and surgeons were present in 69% and 50% of the teams, respectively. All centers responded that the final decision to initiate ECMO is multidisciplinary and made bedside at the referring hospital. Most centers (75%) have a quality control system; all teams practice simulation and water drills. Considering the variability in ECMO transport teams among experienced centers, continuous education, training and quality control within each organization itself are necessary to avoid adverse events and maintain a low mortality rate. A specific international ECMO Transport platform to share data, benchmark outcomes, promote standardization, and provide quality control is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000000997DOI Listing
February 2020

Splenic development and injury in premature lambs supported by the artificial placenta.

J Pediatr Surg 2019 Jun 1;54(6):1147-1152. Epub 2019 Mar 1.

Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, MI; Fetal Diagnosis and Treatment Center, C.S. Mott Children's Hospital, Michigan Medicine, Ann Arbor, MI.

Introduction: The purpose of this study is to evaluate splenic effects during artificial placenta (AP) support.

Methods: AP lambs (118-121 d, n = 14) were delivered and placed on the AP support for a goal of 10-14 days. Cannulation used right jugular drainage and umbilical vein reinfusion. Early (ETC; 115-120 d; n = 7) and late (LTC; 125-131 d; n = 7) tissue controls were delivered and immediately sacrificed. Spleens were formalin fixed, H&E stained, and graded for injury, response to inflammation, and extramedullary hematopoiesis (EMH). CD68 and CD163 stains were used to assess for macrophage activation and density. Clinical variables were correlated with splenic scores. Groups were compared using Fisher's Exact Test and descriptive statistics. p < 0.05 indicated significance.

Results: Mean survival for AP lambs was 12 ± 5 d. There was no necrosis found in any of the groups. Vascular congestion and sinusoidal histiocytosis did not significantly differ between AP and control groups (p = 0.72; p = 0.311). There were significantly more pigmented macrophages (p = 0.008), CD163 (p = <0.001), and CD68 (p = <0.001) stained cells in the AP group. ETC and LTC demonstrated more EMH than AP spleens (p = <0.001).

Conclusions: During AP support, spleens appear to develop normally and exhibit an appropriate inflammatory response. After initiation of AP support, EMH transitions away from the spleen.

Study Type: Research Paper/Therapeutic Potential.

Level Of Evidence: N/A.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpedsurg.2019.02.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545267PMC
June 2019

The ELSO Maastricht Treaty for ECLS Nomenclature: abbreviations for cannulation configuration in extracorporeal life support - a position paper of the Extracorporeal Life Support Organization.

Crit Care 2019 Feb 8;23(1):36. Epub 2019 Feb 8.

Louisiana State University Health Sciences Center, Shreveport, LA, USA.

Background: The Extracorporeal Life Support Organization (ELSO) Maastricht Treaty for Nomenclature in Extracorporeal Life Support (ECLS) established consensus nomenclature and abbreviations for ECLS to ensure accurate, concise communication.

Methods: We build on this consensus nomenclature by layering a framework of precise and efficient abbreviations for cannula configuration that describe flow direction, number of cannulae used, any additional ECLS-related catheters, and cannulation sites. This work is a consensus of international representatives of the ELSO, including those from the North American, Latin American, European, South and West Asian, and Asian-Pacific chapters of ELSO.

Results: The classification increases in descriptive capability by introducing a third (cannula tip position) and fourth (cannula dimension) level to those provided in the previous consensus on ECLS cannulation configuration nomenclature. This expansion offers the simplest level needed to convey cannulation information yet allows for more details when required.

Conclusions: A complete nomenclature for ECLS cannulation configurations accommodating future revisions was developed to facilitate ability to compare practices and results, to promote efficient communication, and to improve quality of registry data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-019-2334-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367794PMC
February 2019

An Artificial Placenta Protects Against Lung Injury and Promotes Continued Lung Development in Extremely Premature Lambs.

ASAIO J 2019 Sep/Oct;65(7):690-697

From the Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, Michigan.

An artificial placenta (AP) utilizing extracorporeal life support (ECLS) could protect premature lungs from injury and promote continued development. Preterm lambs at estimated gestational age (EGA) 114-128 days (term = 145) were delivered by Caesarian section and managed in one of three groups: AP, mechanical ventilation (MV), or tissue control (TC). Artificial placenta lambs (114 days EGA, n = 3; 121 days, n = 5) underwent venovenous (VV)-ECLS with jugular drainage and umbilical vein reinfusion for 7 days, with a fluid-filled, occluded airway. Mechanical ventilation lambs (121 days, n = 5; 128 days, n = 5) underwent conventional MV until failure or maximum 48 hours. Tissue control lambs (114 days, n = 3; 121 days, n = 5; 128 days, n = 5) were sacrificed at delivery. At the conclusion of each experiment, lungs were procured and sectioned. Hematoxylin and eosin (H&E) slides were scored 0-4 in seven injury categories, which were summed for a total injury score. Slides were also immunostained for platelet-derived growth factor receptor (PDGFR)-α and α-actin; lung development was quantified by the area fraction of double-positive tips of secondary alveolar septa. Support duration of AP lambs was 163 ± 9 (mean ± SD) hours, 4 ± 3 for early MV lambs, and 40 ± 6 for late MV lambs. Total injury scores at 121 days were 1.7 ± 2.1 for AP vs. 5.5 ± 1.6 for MV (p = 0.02). Using immunofluorescence, double-positive tip area fraction at 121 days was 0.017 ± 0.011 in AP lungs compared with 0.003 ± 0.003 in MV lungs (p < 0.001) and 0.009 ± 0.005 in TC lungs. At 128 days, double-positive tip area fraction was 0.012 ± 0.007 in AP lungs compared with 0.004 ± 0.004 in MV lungs (p < 0.001) and 0.016 ± 0.009 in TC lungs. The AP is protective against lung injury and promotes lung development compared with mechanical ventilation in premature lambs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000000939DOI Listing
June 2020

Inflammatory Effects of Blood-Air Interface in a Porcine Cardiopulmonary Bypass Model.

ASAIO J 2020 01;66(1):72-78

Department of Cardiac Surgery, Michigan Medicine, University of Michigan, Ann Arbor, Michigan.

Cardiopulmonary bypass (CPB) causes a systemic inflammatory response syndrome (SIRS) associated with multiorgan injury. A model was developed to test whether a blood-air interface (BAI) in the CPB circuit causes blood element activation and inflammation. Ten healthy swine were placed on partial CPB for 2 hours via the cervical vessels and monitored for 96 hours postoperatively. Five pigs (control group) had minimal air exposure in the circuit, while five were exposed to a BAI simulating cardiotomy suction. There were no significant differences in bypass flow or hemodynamics between the groups. In the BAI group, there was an increase in hemolysis after bypass (plasma-free hemoglobin 5.27 ± 1.2 vs. 0.94 ± 0.8 mg/dl; p = 0.01), more aggressive platelet consumption (28% vs. 83% of baseline; p = 0.009), leukocyte consumption (71% vs. 107% of baseline; p = 0.02), and increased granulocyte CD11b expression (409% vs. 106% of baseline; p = 0.009). These data suggest the inflammatory pattern responsible for the CPB-SIRS phenomenon may be driven by blood-air interaction. Future efforts should focus on BAI-associated mechanisms for minimizing blood trauma and inflammation during CPB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000000938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581643PMC
January 2020

Nitric oxide-releasing semi-crystalline thermoplastic polymers: preparation, characterization and application to devise anti-inflammatory and bactericidal implants.

Biomater Sci 2018 Nov;6(12):3189-3201

Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.

Semi-crystalline thermoplastics are an important class of biomaterials with applications in creating extracorporeal and implantable medical devices. In situ release of nitric oxide (NO) from medical devices can enhance their performance via NO's potent anti-thrombotic, bactericidal, anti-inflammatory, and angiogenic activity. However, NO-releasing semi-crystalline thermoplastic systems are limited and the relationship between polymer crystallinity and NO release profile is unknown. In this paper, the functionalization of poly(ether-block-amide) (PEBA), Nylon 12, and polyurethane tubes, as examples of semi-crystalline polymers, with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) within, is demonstrated via a polymer swelling method. The degree of crystallinity of the polymer plays a crucial role in both SNAP impregnation and NO release. Nylon 12, which has a relatively high degree of crystallinity, exhibits an unprecedented NO release duration of over 5 months at a low NO level, while PEBA tubing exhibits NO release over days to weeks. As a new biomedical application of NO, the NO-releasing PEBA tubing is examined as a cannula for continuous subcutaneous insulin infusion. The released NO is shown to enhance insulin absorption into the bloodstream probably by suppressing the tissue inflammatory response, and thereby could benefit insulin pump therapy for diabetes management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8bm00849cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246781PMC
November 2018

Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: EOLIA and Beyond.

Crit Care Med 2019 01;47(1):114-117

Department of Surgery, University of Michigan, Ann Arbor, MI.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000003444DOI Listing
January 2019

The artificial placenta: Continued lung development during extracorporeal support in a preterm lamb model.

J Pediatr Surg 2018 Oct 8;53(10):1896-1903. Epub 2018 Jun 8.

Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, B560 MSRB II/SPC 5686, 1150 W. Medical Center Dr., Ann Arbor, MI, USA; Fetal Diagnosis and Treatment Center, C.S. Mott Children's Hospital, Michigan Medicine, 1540 E. Medical Center Dr., Ann Arbor, MI.

Purpose: An artificial placenta (AP) utilizing extracorporeal life support (ECLS) could avoid the harm of mechanical ventilation (MV) while allowing the lungs to develop.

Methods: AP lambs (n = 5) were delivered at 118 days gestational age (GA; term = 145 days) and placed on venovenous ECLS (VV-ECLS) with jugular drainage and umbilical vein reinfusion. Lungs remained fluid-filled. After 10 days, lambs were ventilated. MV control lambs were delivered at 118 ("early MV"; n = 5) or 128 days ("late MV"; n = 5), and ventilated. Compliance and oxygenation index (OI) were calculated. After sacrifice, lungs were procured and H&E-stained slides scored for lung injury. Slides were also immunostained for PDGFR-α and α-actin; alveolar development was quantified by the area fraction of alveolar septal tips staining double-positive for both markers.

Results: Compliance of AP lambs was 2.79 ± 0.81 C compared to 0.83 ± 0.19 and 3.04 ± 0.99 for early and late MV, respectively. OI in AP lambs was lower than early MV lambs (6.20 ± 2.10 vs. 36.8 ± 16.8) and lung injury lower as well (1.8 ± 1.6 vs. 6.0 ± 1.2). Double-positive area fractions were higher in AP lambs (0.012 ± 0.003) than early (0.003 ± 0.0005) and late (0.004 ± 0.002) MV controls.

Conclusions: Lung development continues and lungs are protected from injury during AP support relative to mechanical ventilation.

Level Of Evidence: n/a (basic/translational science).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpedsurg.2018.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151273PMC
October 2018

The effect of air exposure on leucocyte and cytokine activation in an in-vitro model of cardiotomy suction.

Perfusion 2018 10 11;33(7):538-545. Epub 2018 Apr 11.

Department of Surgery, Extracorporeal Life Support Laboratory, University of Michigan, Ann Arbor, MI, USA.

Introduction: Cardiopulmonary bypass (CPB) is known to cause a systemic inflammatory and immune response.

Objective: An in-vitro model of cardiotomy suction was designed to quantify the effects of incrementally increased air-blood exposure on leucocyte marker CD11b and cytokine activation in two common anticoagulants, heparin and citrate.

Methods: Fresh human blood was exposed to increasing amounts of air flow for ten minutes. Leucocyte and cytokine levels were measured prior to and after ten minutes of air flow. Cytokine levels were also measured after air exposure when incubated for 24 hours at 37C.

Results: Leucocyte activation, measured by CD11b, was elevated between baseline and air flow rates up to 50 mL/min. After 10 minutes of air exposure, no measured cytokine levels were elevated. After 24 hours of incubation, cytokine levels of TNFα, IL-10, IL-6, and IL-8 were elevated. However, only IL-8 was significantly elevated in citrated blood, but not in heparinized blood, when compared to baseline samples that were also incubated for 24 hours.

Conclusion: This study investigates CD11b levels in response to an air stimulus in blood that was anticoagulated with citrate or heparin. Exposure to an air stimulus activates leucocytes. Activation of CD11b was less when using heparin as an anticoagulant compared to citrate. Cytokine activation occurs with air stimulation, but levels do not immediately rise, indicating that time is required to generate free cytokines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0267659118766157DOI Listing
October 2018

The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support. A Position Paper of the Extracorporeal Life Support Organization.

Am J Respir Crit Care Med 2018 08;198(4):447-451

21 Department of Surgery, University of Michigan, Ann Arbor, Michigan.

Extracorporeal life support (ECLS) was developed more than 50 years ago, initially with venoarterial and subsequently with venovenous configurations. As the technique of ECLS significantly improved and newer skills developed, complexity in terminology and advances in cannula design led to some misunderstanding of and inconsistency in definitions, both in clinical practice and in scientific research. This document is a consensus of multispecialty international representatives of the Extracorporeal Life Support Organization, including the North America, Latin America, EuroELSO, South West Asia and Africa, and Asia-Pacific chapters, imparting a global perspective on ECLS. The goal is to provide a consistent and unambiguous nomenclature for ECLS and to overcome the inconsistent use of abbreviations for ECLS cannulation. Secondary benefits are ease of multicenter collaboration in research, improved registry data quality, and clear communication among practitioners and researchers in the field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.201710-2130CPDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118026PMC
August 2018

Gastrointestinal mucosal development and injury in premature lambs supported by the artificial placenta.

J Pediatr Surg 2018 Jun 8;53(6):1240-1245. Epub 2018 Mar 8.

Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, MI; Fetal Diagnosis and Treatment Center, C.S. Mott Children's Hospital, Michigan Medicine, Ann Arbor, MI.

Background: An Artificial Placenta (AP) utilizing extracorporeal life support (ECLS) could revolutionize care of extremely premature newborns, but its effects on gastrointestinal morphology and injury need investigation.

Methods: Lambs (116-121days GA, term=145; n=5) were delivered by C-section, cannulated for ECLS, had total parenteral nutrition (TPN) provided, and were supported for 7days before euthanasia. Early and Late Tissue Controls (ETC, n=5 and LTC, n=5) delivered at 115-121days and 125-131days, respectively, were immediately sacrificed. Standardized jejunal samples were formalin-fixed for histology. Crypt depth (CD), villus height (VH), and VH:CD ratios were measured. Measurements also included enterocyte proliferation (Ki-67), Paneth cell count (Lysozyme), and injury scores (H&E). ANOVA and Chi Square were used with p<0.05 considered significant.

Results: CD, VH, and VH:CD were similar between groups (p>0.05). AP demonstrated more enterocyte proliferation (95.7±21.8) than ETC (49.4±23.4; p=0.003) and LTC (66.1+11.8; p=0.04), and more Paneth cells (81.7±17.5) than ETC (41.6±7.0; p=0.0005) and LTC (40.7±8.2, p=0.0004). Presence of epithelial injury and congestion in the bowel of all groups were not statistically different. No villus atrophy or inflammation was present in any group.

Conclusions: This suggests preserved small bowel mucosal architecture, high cellular turnover, and minimal evidence of injury.

Study Type: Research paper/therapeutic potential.

Level Of Evidence: N/A.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpedsurg.2018.02.092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994371PMC
June 2018