A 40 year old lady was admitted under the medical team with pneumonia. She was normally well with no history of respiratory illnesses. On day two of her hospital admission she became more hypoxic necessitating continuous-positive-airway-pressure. Her condition rapidly worsened and her chest x-ray showed diffuse bilateral infiltrates. An echocardiogram demonstrated normal systolic function. She was intubated and ventilated. Despite sedation, ARDSnet ventilation, paralysis and then proning her, she remained severely hypoxaemic. A therapeutic bronchoscopy was performed prior to proning but did not improve her condition.

Should she be referred for consideration of ECMO and was is this evidence to support it’s use?

Dave Slessor

ECMO is an extracorporeal circuit that directly oxygenates and removes CO2 from blood.¹ It can be either veno-venous or veno-arterial (VA). VV-ECMO is recommended for respiratory failure when cardiac function is adequate or mildly depressed.² Whereas VA-ECMO is used when cardiac support is also required. The advantages of VV, in comparison to VA-ECMO, include the avoidance of cannulating a major artery and a lower risk of systemic embolism.³

In VV-ECMO deoxygenated blood is removed and passed through an oxygenator and a heat exchanger.³ Gas exchange occurs across a permeable membrane with blood on one side and a sweep gas on the other. The sweep gas is normally 100% oxygen or carbogen (5% CO2, 95% oxygen).² The rate of CO2 removal is determined by the sweep flow rate (SFR) whereas the rate of oxygenation is dependent on the blood flow rate (BFR). As the BFR increases a greater proportion of the cardiac output passes through the ECMO circuit and is therefore oxygenated.¹ A pump is then used to return oxygenated blood back into the venous circulation.³ Access can be gained through the use of two single-lumen cannula with blood removed from either an internal jugular or femoral line and then returned via a femoral line. More recently a double-lumen cannula has been developed that can be placed in the internal jugular vein. Due to the position of the ports, in comparison with single-lumen cannula, it has the advantage that it minimises recirculation of oxygenated blood back through the ECMO circuit.³ Both approaches normally utilise the Seldinger technique. Alternatively placement can be achieved via a cut-down technique or through direct placement during cardiac surgery.³

Heparin is given at the time of cannulation and a systemic infusion is used to try and prevent clotting within the circuit.¹

Through the use of ECMO lung protective MV strategies can be utilised that limit the damage caused by volutrauma, barotrauma and oxygen toxicity.³

Indications

The indications for ECMO for adult respiratory failure are:²

1. Hypoxic respiratory failure (PaO2/FiO2 <80 on FiO2 >90% and Murray score 3-4. This is predictive of an 80% mortality risk without ECMO)
2. Severe air leak syndromes
3. CO2 retention due to asthma/permissive hypercapnia (PaCO2>80mmHg or plateau pressure>30cmH2O)

It should also be considered if the PaO2/FiO2 <150 on a FiO2>90% and/or Murray score 2-3.² This is predictive of a 50% mortality risk without ECMO.²

There are no absolute contraindications, but relative contraindications include MV at high settings for ≥7 days, intra-cranial haemorrhage (ICH) or major immunosuppresion.²

Complications

Complications include:

• directly related to the ECMO circuit: oxygenator failure (17.5%) blood clots (12.2-17.8%)¹ gas embolism (1.6-1.8%).³
• indirectly related to the ECMO circuit: surgical site bleeding (19%), ICH (3.8%); haemolysis (6.9%), infection (21.3%).¹

Evidence

The first randomised controlled trial (RCT) was published in 1979 comparing ECMO with conventional treatment in ninety patients with respiratory failure.⁴ Dismal results were reported in both groups with mortality rates at 91.7% and 90.5% respectively. Another RCT compared standard care with inverse-ratio MV followed by extracorporeal CO2 removal.⁵ Again no difference in mortality was found (42% vs. 33%, P=0.8). However both of these trials used ventilation and perfusion techniques that are very different from modern techniques.

More recently the CESAR study compared standard treatment with transfer to a specialist centre for consideration of ECMO in 180 patients with reversible severe respiratory failure.⁶ Inclusion criteria included a Murray score of ≥3 or uncompensated hypercapnoea with a pH <7.2 despite optimal treatment. They demonstrated a significant reduction in the composite outcome of death or severe disability at six months in the intervention, compared with the control group (37% vs. 53%, P=0.03). However only 76% of those patients referred for consideration of ECMO actually received ECMO. Seventeen patients improved with conventional MV of whom fourteen survived. If these same improvements had been made in the control group the result would have been statistically non-significant. Therefore it may have been the treatment in a specialist centre rather than ECMO that improved outcomes. Of note there was only one serious complication in patients treated with ECMO when a vessel perforation occurred that was felt to contribute to death.

Davies reported the results of 68 patients treated with ECMO for H1N1.⁷ Their lowest median PaO2/FiO2 ratio was 56 (Inter-quartile range (IQR) 48-63). The mortality was 21% at the end of the study period, at which point 32% of patients were still in hospital. Haemorrhagic complications occurred in 54% of patients, leading to death in at least 13% of patients.

Noah demonstrated a lower mortality in patients that were accepted for ECMO for H1N1 compared with a propensity-matched group that were not referred for ECMO.⁸ (23.7% vs. 50.7%, P=0.001) Their lowest mean PaO2/FiO2 ratio was 54.9. However, this study suffered from a number of limitations including non-randomisation and the limited information recorded on patients not referred. For example we are not told if these patients were treated with lung protective MV strategies. Of note 10% of the patients referred for ECMO died from haemorrhage.

In comparison Miller reported 30 patients with ARDS from H1N1 that were not treated with ECMO.⁹ Their lowest median PaO2/FiO2 ratio was 61 (IQR 52-100). The mortality was 27%, which is not statistically different from Davies or Noah’s studies.

Weaning

Weaning from ECMO may occur when there have been improvements in lung compliance, arterial oxygen saturation and chest x-ray findings.³ MV is set at standard levels and then the ECMO BFR and SFR are decreased and then stopped. If after a period of observation off ECMO the patient remains stable they are decannulated.³

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References

1. Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. New England Journal of Medicine. 2011;365(20):1905-14.
2. Extracorporeal Life Support Organization guidelines [cited 1st July 2013].
3. Hung M, Vuylsteke A, Valchanov K. Extracorporeal membrane oxygenation: coming to an ICU near you. Journal of the Intensive Care Society. 2012;13:31-7.
4. Zapol WM, Snider MT, Hill JD, Fallat RJ, Bartlett RH, Edmunds LH, et al. Extracorporeal membrane oxygenation in severe acute respiratory failure. JAMA: the journal of the American Medical Association. 1979;242(20):2193-6.
5. Morris A, Wallace C, Menlove R, Clemmer T, Orme Jr J, Weaver L, et al. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. American Journal of Respiratory and Critical Care Medicine. 1994;149(2):295-305.
6. Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet (London, England). 2009;374(9698):1351-63.
7. Davies A, Jones D, Bailey M, Beca J, Bellomo R, Blackwell N, et al. Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome. JAMA: the journal of the American Medical Association. 2009;302(17):1888-95.
8. Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A (H1N1). JAMA: the journal of the American Medical Association. 2011;306(15):1659-68.
9. Miller RR, Markewitz BA, Rolfs RT, Brown SM, Dascomb KK, Grissom CK, et al. Clinical findings and demographic factors associated with ICU admission in Utah due to novel 2009 influenza A (H1N1) infection. CHEST Journal. 2010;137(4):752-8.

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