By Jane Guttendorf, DNP, CRNP, ACNP-BC, CCRN

Assistant Professor, Acute & Tertiary Care, University of Pittsburg School of Nursing

Dr. Guttendorf reports no financial relationships relevant to this field of study.

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure in a heterogeneous population of patients associated with acute onset of bilateral pulmonary infiltrates and severe hypoxemia not associated with cardiac failure. ARDS continues to be common in ICU patients and carries a high associated mortality. In the era of lung-protective ventilation strategies for ARDS, mortality has declined, but remains high. In a recent systematic review, the in-hospital mortality rate for ARDS since 2010 was 45%.1 The ALIEN study, a one-year prospective evaluation of the incidence and mortality associated with ARDS in ICUs in Spain, reported hospital mortality of 47.8%.2

Extracorporeal membrane oxygenation (ECMO) has been used as a rescue therapy for patients with severe ARDS who fail to respond to traditional low tidal volume lung protective ventilation with optimal positive end-expiratory pressure (PEEP) interventions and other strategies, including prone positioning, high frequency oscillatory ventilation, neuromuscular blockade, and inhaled nitric oxide or epoprostenol.

The first use of ECMO for adult respiratory failure was reported in 1972 in a trauma patient with shock lung who was supported with venoarterial ECMO for 75 hours and survived.3 Following that, there were several efforts to conduct randomized, controlled trials to study the use of ECMO for respiratory support in adults; but overall, those studies reported unfavorable results, and most centers abandoned efforts.4-6 Then, with improvements in technology, primarily in pumps and oxygenators, and continued success in neonates and children, efforts resurfaced to apply the technology to adults. Between 1997 and 2009, a number of single-center and registry reports demonstrated improvement in survival of ECMO for respiratory failure to about 50%, which, at the time, was an improvement over the expected survival for a patient with ARDS treated with conventional therapies.7-11 The CESAR trial, conducted in 2009, was a randomized, controlled trial of referral for ECMO therapy vs. conventional support in adults with severe ARDS. The trial reported increased survival without disability at six months with survival in the referral for ECMO group at 63%, compared with those not referred at 47% (relative risk [RR], 0.69; 95% confidence interval [CI], 0.05-0.97; P = 0.03).12 Although the trial was criticized for the lack of standardized therapy in the control arm, the overall results were very favorable for the use of ECMO for severe ARDS with improvement in survival. This prompted more widespread use of this technology in adults. Likewise, the successful treatment of increased numbers of patients with influenza-associated ARDS during the H1N1 influenza pandemic of 2009 led to an increase in the number of centers performing ECMO in adults and a sharp rise in the number of adult patients treated with ECMO.

Tsai et al reported a single-center, retrospective, case-controlled study matching ARDS patients over a six-year period by age and APACHE II scores in both ECMO and non-ECMO treatment groups and demonstrated improved hospital survival and lower six-month mortality (P < 0.001) in patients presenting with ARDS treated with ECMO compared to those not treated with ECMO, suggesting that ECMO may be beneficial over standard medical therapy for ARDS.13 The Extracorporeal Life Support Organization (ELSO) maintains a registry of ECMO or extracorporeal life support (ECLS) cases by voluntary reporting from centers worldwide. As of January 2017, cumulative adult respiratory ECLS cases numbered 12,346, with 57% of patients surviving to hospital discharge.14

INDICATIONS

The primary indication for ECMO in adults is hypoxic respiratory failure with a potentially reversible cause that is refractory to conventional and rescue treatments with optimal care for six hours or more. ECMO is indicated when the PaO2/FiO2 ratio is < 100-150 on fraction of inspired oxygen (FiO2) of 90% or greater and Murray lung injury score of 3-4. Other indications for respiratory support include hypercarbic respiratory failure with pH 7.20, severe air leak syndromes (such as bronchopleural fistula), patients awaiting lung transplant, and patients experiencing sudden cardiac or respiratory collapse.15

There are few absolute contraindications to ECMO support, but the reversible nature of the primary disorder should be considered carefully. Relative contraindications include duration of mechanical ventilation at high settings for longer than seven days, major pharmacologic immunosuppression, recent or expanding central nervous system hemorrhage, and increased age, as multiple studies have shown increasing age as a predictor of poorer outcome.

CIRCUIT AND CANNULATION

Large cannulas are placed in the patient’s blood vessels to continuously route blood out of the body (extracorporeal) through a circuit that includes, at a minimum a pump, an oxygenator, and a heat exchanger. Additional circuit configurations are possible and can include access ports for drawing samples and administering medications, a reservoir for fluid administration, and in-line point-of-care blood sampling.

Blood is drawn from the patient via a venous drainage cannula aided by a centrifugal pump, routed through a membrane oxygenator where oxygen and carbon dioxide are exchanged, then returned to the patient via either a venous return cannula or an arterial return cannula. An integral heat exchanger is a mandatory circuit component to prevent excessive heat loss as the blood transits extracorporeally. Other extracorporeal circuits can be integrated easily into the ECMO circuit as needed for continuous renal replacement therapy or plasmapheresis.

The type of support (respiratory or cardiac) depends on the placement of the cannulas. Venovenous cannulation provides respiratory support, whereas venoarterial cannulation provides either cardiac support or respiratory support. Common venovenous cannulation techniques include femoral vein to femoral vein, femoral vein to internal jugular (IJ) vein, or a double lumen IJ vein cannula. Common venoarterial cannulation techniques in adults include femoral vein to femoral artery performed percutaneously or via cutdown. With this peripheral cannulation technique, blood is returned via the femoral artery and supplies the aorta and upper extremity vessels in a retrograde fashion. To prevent distal limb ischemia with peripheral venoarterial cannulation, frequently a smaller bore cannula is placed from the arterial return cannula to provide directed antegrade (femoral artery or superficial femoral artery) or retrograde (posterior tibial artery) perfusion to the distal extremity. An alternative to peripheral venoarterial cannulation is placement of cannulas centrally via sternotomy, from right atrium to aorta. Central cannulation provides antegrade return via the ascending aorta, and often can permit larger cannula size.

MOBILITY AND AMBULATION

The bicaval double lumen venous cannula placed via the IJ vein contains two inlets, one in the superior vena cava and one in the inferior vena cava, and a single return port that directs flow into the right atrium and across the tricuspid valve. This cannula is placed under either fluoroscopic or echocardiographic guidance to assure correct positioning. For adults, 27 or 31 French cannula size can facilitate blood flows of 5 to 6 liters per minute. One primary advantage of using the single bicaval dual lumen catheter is patient mobility. Patients can be mobilized easily to sit out of bed in the chair and to exercise and ambulate. This has revolutionized ECMO care, in particular for patients cannulated as a bridge to lung transplant. Patients who tolerate it can be managed with little to no sedation, participate in aggressive physical conditioning programs, and even improve their functional status while awaiting transplant. The bicaval IJ cannula also facilitates prone positioning while on ECMO in patients who require additional recruitment techniques. Whenever possible, patients with ARDS should be cannulated in a venovenous configuration, as outcomes are better than those patients requiring venoarterial cannulation for respiratory support. From the January 2016 ELSO registry data, patients with respiratory failure with venovenous cannulations experienced slightly improved survival (59-65%) over those patients requiring venoarterial cannulation for a respiratory indication who had survival rates of 43-46%.16

ANTICOAGULATION

Anticoagulation is required to prevent thrombosis in the circuit and in venoarterial cannulation ECMO to prevent cardiac thrombus formation since most blood flow is deflected away from the non-beating heart (or one generating minimal pulsatility). Generally, either heparin infusion or a direct thrombin inhibitor (such as bivalirudin) is used. Activated clotting time, partial thromboplastin time, or anti-Xa levels can be used to monitor anticoagulation. Protamine infusion should be avoided due to clotting risk, as most cannula and tubing are heparin-bonded. Similarly, fresh frozen plasma, platelets, and cryoprecipitate may increase risk of clotting in the system (oxygenator, pump, or cannula).

OUTCOMES AND SPECIAL POPULATIONS

Survival is in part related to diagnosis. Viral, bacterial, and aspiration pneumonia have reported survival between 61-66%, while ARDS, non-ARDS acute respiratory failure, and trauma-associated ARDS survival have been reported to be around 54-56%.16

ECMO FOR INFLUENZA A (H1N1)

As mentioned, the H1N1 pandemic of 2009 prompted an increase in the use of ECMO. This experience is summarized in Table 1.17-28 Of these studies, with the exception of the Japanese study (Takeda et al; survival of 36%), survival ranges from 67-86%. For those studies reporting mortality, only one demonstrated significantly lower mortality with ECMO (Noah 2011; ECMO vs. non-ECMO of 24% vs. 53%, respectively).22 A systematic review and meta-analysis in 2013 evaluating the use of ECMO for H1N1 patients included eight studies consisting of 266 patients. Results included a wide-ranging mortality of between 8% and 65%. The pooled estimate of mortality overall was 28% (95% CI, 18-37%; I2 = 64%).28

In addition to the more traditional indications for ECMO (e.g., ARDS, pneumonia, influenza, bridge to lung transplant), there has been growing support for the use of ECMO for a number of other categories of patients with increasing success, including pregnancy, trauma patients with acute lung injury and transfusion-related lung injury, sepsis and septic shock, post-lung transplant primary graft dysfunction, and acute pulmonary embolism.

ECMO IN TRAUMA

At least five studies have been about trauma patients receiving ECMO with good outcomes. In trauma, because of the risk of bleeding, some centers reported using pumpless systems and high flows to avoid anticoagulation. Of these studies, the overall survival ranged from 60-79%.29-32 Guirand et al reported that adjusted survival was greater in the ECLS group (adjusted odds ratio, 0.193; 95% CI, 0.042-0.884; P = 0.034).33

ECMO FOR SEPTIC SHOCK

The experience with septic shock shows more varied results. Of four studies included, 106 patients were treated with ECMO, with survival ranging from 15-70%, with the larger studies of 52 and 32 patients reporting lower survival at 15% and 22%, respectively.34-37 Although the numbers are not large and the populations are not homogeneous, it looks as though ECMO provides benefit in at least some of these patients with sepsis and septic shock. Careful patient selection will be important in determining which patients with sepsis will benefit from ECMO support.

ECMO IN PREGNANCY

A systematic review included 26 papers over 25 years looking at the use of ECMO in pregnancy. It yielded 45 patients with the primary indication H1N1 influenza.38 Overall, maternal survival was 78%, and fetal survival was 65%. The majority of patients were treated with venovenous cannulation ECMO for respiratory failure.

ECMO FOR MASSIVE PULMONARY EMBOLISM

Another systematic review looking at the use of ECMO in massive pulmonary embolus patients included 19 studies over 20 years (78 patients).39 Overall survival was 70%. Only three studies included 10 patients, so individual center experience was low. Overall, the duration of ECMO was relatively short (average one to 12 days), and not surprisingly, each of the single case reports survived. Of the three studies involving 10 patients, survival was 62% (n = 21), 83% (n = 12), and 70% (n = 10). These single-center reports likely also included some selection bias related to each center’s comfort with emergent cannulation for acute pulmonary embolism, changing medical therapies over this period of time (e.g., embolectomy, catheter embolectomy, thrombolysis), and patient selection. There was no difference in mortality among the various treatment modalities for pulmonary embolism (surgical embolectomy, catheter embolectomy, thrombolysis).39

CONCLUSION

The indications for ECMO continue to expand in patients with severe ARDS. Timely recognition of patients failing to respond to standard rescue therapies should prompt early evaluation for ECMO support. Minimizing days on mechanical ventilation prior to instituting ECMO is associated with better outcomes. As ECMO outcomes continue improving, it is important for clinicians to feel comfortable with the range of etiologies of respiratory failure for which ECMO may be beneficial.

REFERENCES

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Table 1: ECMO for Influenza A (H1N1) Summary

Year

Author

N

Survival

Mortality

Design

2009

ANZ-ECMO18

68

71%

 

Observational; Australia, New Zealand; multicenter

2010

Chan19

7

86%

 

Observational; Hong Kong; multicenter

2010

Freed20

6

67%

 

6 ECMO of 168 H1N1 pts. Cohort; Canadian; multicenter

2010

Roch21

9

56%

 

9 ECMO of 18 H1N1 pts. France; single center. No change in survival ECMO or non-ECMO groups.

2010

Holzgraefe22

13

92%
(3 months)

 

Observational; Karolinska Institutet (Sweden), ECMO Referral Center

2011

Noah23

150

 

24% ECMO
53% control

Cohort; matched pairs

2011

Patroniti24

60

68%

 

Prospective cohort; Italy; multicenter

2012

Takeda25

14

36%

 

Observational; Japan; multicenter

2012

Hou26

9

56%

 

Observational; Beijing, China; single center

2013

Pham27

123 ECMO
53 matched

 

50% ECMO
40% control

Cohort, propensity matched

2013

Weber-Carstens28

61

 

54% ECMO
38% overall

61 ECMO of 116 H1N1 pts. German; multicenter

2013

Zangrillo29

266

 

28%

Systematic review and meta-analysis. Eight studies (n = 266). Mortality ranged 8-65%. Pooled mortality, 28% (95% CI, 18-37%; I2 = 64%)