ECMO year in review: transports, infections & sepsis, bleeding and hemostasis on ECLS

ECMO transports

Interhospital ECMO transport: safe & effective with minimal complications and favourable outcomes when performed at an experienced referral center using stringently applied protocols according to the experience of adult patients transported while on extracorporeal support to Columbia University Medical Center; findings might not be applicable to new programs with low ECLS volume/limited referral base.

Tipograf Y, Liou P, Oommen R, Agerstrand C, Abrams D, Brodie D, Bacchetta M. A decade of interfacility extracorporeal membrane oxygenation transport. J Thorac Cardiovasc Surg. 2019 Apr;157(4):1696-1706. link

PS full talk open access here link

Salvage VA ECMO retrieval service for patients with cardiogenic shock: learning from severe respiratory failure service organization? this experience describes the institution of extracorporeal support in the referring hospital, patient management and outcomes, demonstrating feasibility and survival benefit of transferring carefully selected patients with refractory cardiogenic shock on veno-arterial ECLS, even for long distances and with an open chest.

Ali JM, Vuylsteke A, Fowles JA, Pettit S, Salaunkey K, Bhagra S, Lewis C, Parameshwar J, Kydd A, Patvardhan C, Jones N, Rubino A, Abu-Omar Y, Sudarshan C, Tsui S, Catarino P, Jenkins DP, Berman M. Transfer of Patients With Cardiogenic Shock Using Veno-Arterial Extracorporeal Membrane Oxygenation. J Cardiothorac Vasc Anesth. 2019 May 16. link

ECMO transport, results of an international survey: regulatory oversight is lacking about the validation, structure & quality assurance; the establishment of a dedicated international body to develop platforms for uniform education, training, quality, and equipment standards for ECLS transport is advocated.

Broman LM, Dirnberger DR, Malfertheiner MV, Aokage T, Morberg P, Næsheim T, Pappalardo F, Di Nardo M, Preston T, Burrell AJC, Daly I, Harvey C, Mason P, Philipp A, Bartlett RH, Lynch W, Belliato M, Taccone FS. International Survey on Extracorporeal Membrane Oxygenation Transport. ASAIO J. 2019 Apr 2. link

Interhospital transfer on ECMO support of brain‐dead small weight infant as bridge to procurement: protracting ECLS post BD diagnosis to expand pediatric donors pool vs organ shortage, realizing parents’ donation goal.

Leblanc C, Genuini M, Deho A, Lodé N, Philippe-Chomette P, Hervieux E, Amblard A, Pracros N, Léger PL, Jean S. Successful extracorporeal membrane oxygenation transport of a 4-month-old brain-dead infant for organ donation: A case report. Pediatr Transplant. 2019 Nov;23(7):e13515. link

Interhospital transports of newborns on ECMO, where are we now? basic requirements for education, training & experience are needed to increase performance, with wet-labs mimicking narrow spaces scenario, and high-fidelity simulations for the whole team. Preparing for transport, focusing on safe management, timeouts, checklists & ECLS A-B-C (pump, sweep gas, heater, tubings) are mandatory to increase safety. Where will we go? The introduction of new strategies to support the (extremely) premature, as artificial placenta and prem-ECMO, could increase mobile ECMO volume in the future. Neonatal ECMO transport services should include an out-reach service provided by ELSO centers, reporting data to the Registry for transport quality follow-up and research.

Broman LM. Interhospital Transport on Extracorporeal Membrane Oxygenation of Neonates-Perspective for the Future. Front Pediatr. 2019;7:329. Published 2019 Aug 6. Open access link

Infections, sepsis, septic shock and/on ECLS

Infections & extracorporeal support: commonly precede & frequently identified during the run. Here, a review of current knowledge regarding ECLS-associated infections, focusing on potential risk factors & challenges in the detection, treatment, prevention of infections on ECMO. The review also highlights the need for standardized definitions, consistent detection strategies, and comprehensive descriptions of patient characteristics & outcomes to drawn conclusions about the clinical significance of these infections, and suggest best practices for both prevention and management.
PS: Potential strategies to reduce infections during ECLS??
avoid maintaining ECMO support longer than necessary
use a percutaneous approach for cannulation whenever possible & routinely monitor insertion sites for evidence of infections
consider extubation for those at high risk of VAP, when appropriate
maintain a low threshold to obtain cultures
access the circuit only when absolutely necessary, and with proper sterile technique
sensure therapeutic levels of antimicrobials, when feasible.

Abrams D, Grasselli G, Schmidt M, Mueller T, Brodie D. ECLS-associated infections in adults: what we know and what we don’t yet know. Intensive Care Med. 2019 Nov 25. link

Nosocomial infections on ECMO in neonatal, pediatric, & adult patients: common, appearing to more frequently affect older children and adults, associated with longer duration of the ECLS run and (strongly) associated with adverse outcomes. Risk factors for nosocomial infection other than the duration of extracorporeal support include mechanical/bleeding complications and veno-arterial & central configurations. These the result of a narrative review, reporting a low overall quality of studies in the field, and heterogeneity in study design, case definitions, outcomes (so limited generalizability of findings). Diagnosis of infection appears challenging in this population, with lack of evidence to support the routine screenings (ie cultures or biomarkers); effects of anti-infective preventive measures implementation in ECMO patients scarcely studied, with the epidemiology of infections considerably variable (this, in the authors’ opinion, may be due to changes in clinical practice over the last decades, heterogeneity of the populations, differences in the defining nosocomial infection).

MacLaren G, Schlapbach LJ, Aiken AM. Nosocomial Infections During Extracorporeal Membrane Oxygenation in Neonatal, Pediatric, and Adult Patients: A Comprehensive Narrative Review. Pediatr Crit Care Med. 2019 Oct 31. link

There is a critical need for preventing, early detecting, & treating infections during the ECMO run, as mortality for patients developing these complications on extracorporeal support is two times higher than those without: here results from a survey administered to ECMO centers worldwide, reporting lack of consensus and considerable variability among region/center surrounding prevention, diagnosis & management of infections on ECLS, and emphasizing the need for specific research.

Farrell D, MacLaren G, Schlapbach LJ. Infections on Extracorporeal Life Support in Adults and Children-A Survey of International Practice on Prevention, Diagnosis, and Treatment. Pediatr Crit Care Med. 2019 Jul;20(7):667-671. link

with its accompanying editorial, advocating evidence-based dedicated guidelines to improve outcomes of ECMO patients.

Thiagarajan RR. No Consensus, Wide Variability: State of Infection Management During Extracorporeal Membrane Oxygenation. Pediatr Crit Care Med. 2019 Jul;20(7):684-685. link

Candida BSI rare & occurs late during the course of ECMO support? according to these authors early septic shock is frequent but largely due to bacteria: antifungal therapy should not be part of the first-line empiric antimicrobial therapy in septic shock occurring within first 2 weeks of the run, unless indicated for other comorbilities; consider systemic candidiasis in sepsis under prolonged MCS.

de Roux Q, Botterel F, Lepeule R, Taccone FS, Langeron O, Mongardon N. Candida bloodstream infection under veno-arterial ECMO therapy. Crit Care. 2019;23(1):314. Open access link

in reply Cavayas YA, Yusuff H, Porter R. Fungal infections in adult patients on extracorporeal life support. Crit Care. 2018;22(1):98. link

ECMO in septic shock? Results of this single (ECLS experienced) center analysis of both distributive septic shock and septic shock with cytotoxic cardiac failure, suggests that peripheral cannulation extracorporeal support may be beneficial for hospital & long-term survival, provided that ECLS should be initiated by and/or at least continued at a high-volume center with experience in both veno-venous & veno-arterial configuration, in order to provide proper support, adapted to to patient need.

Falk L, Hultman J, Broman LM. Extracorporeal Membrane Oxygenation for Septic Shock. Crit Care Med. 2019 Aug;47(8):1097-1105. link

Antimicrobials on ECMO? dosing on ECLS run can be challenging, as antibiotics cannot be titrated to clinical effect in real time, and challenges are may further increase if TDM is not readily available: apply the existing knowledge of critical illness-related PK changes and the emerging knowledge of altered PK on extracorporeal support to provide (or strive to provide) optimal pharmacotherapy!

Abdul-Aziz MH, Shekar K, Roberts JA. Antimicrobial therapy during ECMO – customised dosing with therapeutic drug monitoring: The way to go? Anaesth Crit Care Pain Med. 2019 Oct;38(5):451-453. link

Blood on ECLS: bleeding & hemostasis, anticoagulation (and no anticoagulation) & its monitoring, transfusion practices, hemolysis

Bleeding & thrombosis in pediatric ECLS: reviewing knowledge and current & novel medications, and proposing recommendations for future research directions to establish “best practice” for anticoagulation management on ECMO. All centers should report data on patients receiving extracorporeal support to a registry: the ELSO registry remains the primary and most successful data repository.

Penk JS, Reddy S, Polito A, Cisco MJ, Allan CK, Bembea MM, Giglia TM, Cheng HH, Thiagarajan RR, Dalton HJ. Bleeding and Thrombosis With Pediatric Extracorporeal Life Support: A Roadmap for Management, Research, and the Future From the Pediatric Cardiac Intensive Care Society: Part 1. Pediatr Crit Care Med. 2019 Nov;20(11):1027-1033. link
Penk JS, Reddy S, Polito A, Cisco MJ, Allan CK, Bembea M, Giglia TM, Cheng HH, Thiagarajan RR, Dalton HJ. Bleeding and Thrombosis With Pediatric Extracorporeal Life Support: A Roadmap for Management, Research, and the Future From the Pediatric Cardiac Intensive Care Society: Part 2. Pediatr Crit Care Med. 2019 Nov;20(11):1034-1039. link

Should patients on veno-arterial ECLS without other indications for anticoagulation be treated without systemic anticoagulation during extracorporeal support to prevent complications?? In this single center retrospective observation, no routine systemic anticoagulation during the ECMO run is not associated with higher mortality, pump failure, or thrombotic complications; patients required lower blood product transfusions, with no incidence of HIT.

Wood KL, Ayers B, Gosev I, Kumar N, Melvin AL, Barrus B, Prasad S. Venoarterial ECMO Without Routine Systemic Anticoagulation Decreases Adverse Events. Ann Thorac Surg. 2019 Sep 26. link

ECMO without anticoagulation: a series of immunocompromised patients with hemorrhagic tendency due to severe disease-related thrombocytopenia. No fatal clotting reported, with one patient receiving uninterrupted heparin‐free ECMO for really long‐term run (317 days! with only two extracorporeal circuit replacement – over a total of 6 – related to suspected ML thrombosis). Withdrawing systemic anticoagulation could be an appropriate and safe strategy in these population, as clotting events rarely occur, but indication for respiratory ECLS should be critically discussed, as prognosis appears poor.

Hermann A, Schellongowski P, Bojic A, Robak O, Buchtele N, Staudinger T. ECMO without anticoagulation in patients with disease-related severe thrombocytopenia: Feasible but futile? Artif Organs. 2019 Nov;43(11):1077-1084. link

Posterior fossa hemorrhage on VA ECMO support for postcardiotomy refractory cardiogenic shock: report of successful hematoma evacuation in semi-lateral position, avoiding risks of sitting or prone position with femoro-femoral cannulation, and protracted anticoagulant suspension without thrombotic events during ECLS.

Papin G, Sonneville R, Nataf P, Bouadma L. Emergency craniotomy in semi-lateral position for posterior fossa hemorrhage evacuation under venoarterial extracorporeal membrane oxygenation. Intensive Care Med. 2019 Aug;45(8):1152-1153. link

HEparin in critically iLl Patients undergoing ECMO); in this pilot two-center, randomized trial, the allocation to a low-dose or therapeutic dose heparin protocol resulted in a difference in the mean daily dose of UFH & in a significant difference in mean aPTT/anti-Xa; these results, even if not providing evidence on the optimal anticoagulation protocol for extracorporeal support, seem supporting the feasibility of a larger study to evaluate the safety/efficacy of low-dose anticoagulation on VV ECLS.

Aubron C, McQuilten Z, Bailey M, Board J, Buhr H, Cartwright B, Dennis M, Hodgson C, Forrest P, McIlroy D, Murphy D, Murray L, Pellegrino V, Pilcher D, Sheldrake J, Tran H, Vallance S, Cooper DJ; endorsed by the International ECMO Network (ECMONet). Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation: A Pilot Randomized Trial. Crit Care Med. 2019 Jul;47(7):e563-e571. link

Good practice statements & supporting literature for red blood cell transfusions in critically ill children on ECMO, Ventricular Assist Devices or renal replacement therapy RRT from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

Bembea MM, Cheifetz IM, Fortenberry JD, Bunchman T, Valentine S, Bateman S, Steiner M, and for the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) *, in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Recommendations on the Indications for RBC Transfusion for the Critically Ill Child Receiving Support From Extracorporeal Membrane Oxygenation, Ventricular Assist, and Renal Replacement Therapy Devices From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Pediatr Crit Care Med. 2018;19(9S Suppl 1):S157–S162. link

Here, the consensus conference methodology, open access link

A standardized thrombo-elastography & aPTT driven anticoagulation-monitoring protocol on ECMO support: appears safe and feasible in this observation. Rate of major bleeding as defined by ELSO parameters did not differ between the treatment groups, but a significant difference in mortality and retroperitoneal bleeds was observed, potentially suggesting, in the authors’ opinion, an advantage and supporting protocol driven care to avoid over/under anticoagulation in this population.

Colman E, Yin EB, Laine G, et al. Evaluation of a heparin monitoring protocol for extracorporeal membrane oxygenation and review of the literature. J Thorac Dis. 2019;11(8):3325–3335. Open access link

Anti-Xa & aPTT monitoring of heparin in adults on ECMO support: in this retrospective evaluation, anti-Xa assay better correlated with weight based dose vs aPTT; as low anti-Xa values predictive of thrombosis & high aPTT predictive of bleeding, a balanced anti-Xa/aPTT therapeutic drug monitoring approach may be warranted.

Arnouk S, Altshuler D, Lewis TC, Merchan C, Smith DE 3rd, Toy B, Zakhary B, Papadopoulos J. Evaluation of Anti-Xa and Activated Partial Thromboplastin Time Monitoring of Heparin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Support. ASAIO J. 2019 May 10. link

Monitoring hemostasis on ECMO support: comparing different hemostatic assays, PT, PTT, ACT, antifactor Xa, to determine their sensitivity to changes in the levels of coagulation factors, ATIII, UFH, PLTs, Ht analyzing vitro/in vivo data. aXa seems the most specific for heparin levels vs PT for coagulation factor levels, making these assays well suited to monitor patients on extracorporeal support; PTT highly variable as multiple parameters are changing, but may be useful when aXa cannot be used because of interference; ACT too insensitive to UFH and sensitive to too many other factors & too imprecise to be useful.

Saifee NH, Brogan TV, McMullan DM, Yalon L, Matthews DC, Burke CR, Chandler WL. Monitoring Hemostasis During Extracorporeal Life Support. ASAIO J. 2019 Mar 21. link

High Hb & ECLS: report of a case of acute normovolemic hemodilution to improve impaired extracorporeal blood flow with drainage failure possibly linked to severe polycythemia and hyperviscosity in an ARDS patient on veno-venous ECMO support.

Ursulet L, Pierrakos C, Cudia A, Velissaris D, Janssenswillen E, Devriendt J, De Bels. High Hemoglobin Level As a Limiting Factor for Extracorporeal Membrane Oxygenation. D. ASAIO J. 2019 Nov/Dec;65(8):e97-e99. Open access link

Hemolysis on ECMO support: pathophysiology, prevalence (how/when), clinical consequences, clinical & biologic diagnosis, limits to prevent & manage hemolytic events. Despite of major technological improvements ECLS-associated hemolysis still occurs with various intensity, from a nonalarming/tolerable to a highly toxic one.

Dufour N, Radjou A, Thuong M. Hemolysis and Plasma Free Hemoglobin During Extracorporeal Membrane Oxygenation Support: From Clinical Implications to Laboratory Details. A Review. ASAIO J. 2019 Feb 26. link

Membrane Lung induced hyperfibrinolysis as cause of bleeding on ECMO support detected by comparing thromboelastometry results from blood samples obtained before & after oxygenator and successfully treated merely by ML exchange: a case report.

Durila M, Smetak T, Hedvicak P, Berousek J. Perfusion. 2019 May;34(4):330-333. Extracorporeal membrane oxygenation-induced fibrinolysis detected by rotational thromboelastometry and treated by oxygenator exchange. Open access link

Roller vs centrifugal pump in infants on ECMO?? results from a large propensity score–matched cohort study in ECLS recipients weighing less than 10kg within the ELSO registry. Centrifugal pump use, expanding with technological advances & ease of handling, reported as associated with increased inpatient mortality, and increased rates of extracorporeal support related complications (cardiovascular, neurologic, renal, pulmonary, mechanical, hemolytic, infectious, limb). Authors suggest hemolysis may mediate these observations, and that their results may support an ongoing role for rollers in small children needing for ECMO.

O’Halloran CP, Thiagarajan RR, Yarlagadda VV, Barbaro RP, Nasr VG, Rycus P, Anders M, Alexander PMA. Outcomes of Infants Supported With Extracorporeal Membrane Oxygenation Using Centrifugal Versus Roller Pumps: An Analysis From the Extracorporeal Life Support Organization Registry. Pediatr Crit Care Med. 2019 Dec;20(12):1177-1184. link

… and a related comment: how then should we interpret these data? enough to recommend roller pumps for children less than 10 kg? likely no, they state, considering the significant role of hemolysis in mediating observed results, lack of timing of events and potential confounders.

Dalton HJ, Hoskote A. There and Back Again: Roller Pumps Versus Centrifugal Technology in Infants on Extracorporeal Membrane Oxygenation. Pediatr Crit Care Med. 2019 Dec;20(12):1195-1196. link

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: