Extracorporeal Membrane Oxygenation

Case

A 35 year-old female with no PMH is brought in by her mother for acting strangely. Mother notes the patient has had two days of cough and cold-like symptoms with nausea today. She slept all day and upon waking, she was confused and not making any sense.

+fever, +epigastric discomfort, +nausea

 

ROS: Denies sick contacts, recent travel, chest pain, shortness of breath

PSH: None

Meds: None

NKDA

SH: No toxic habits

FH: Noncontributory

 

PE:

VS: HR 136  RR: 22  BP: 90/74  T: 102.7F  SpO₂: 96% RA  Glu: 83

Gen: Appears “dry”, speaking full sentences, trying to leave exam room

HEENT: PERRLA, EOMI, oropharynx clear, TMs clear, no LAD

CV: Tachycardia, no m/r/g, normal S1 and S2

Resp: Coarse breath sounds bilaterally

Abd: Mild tenderness diffusely, intact bowel sounds

Skin: Dry, no rashes

Neuro: Oriented to name, recognizes mother, CN II-XII intact, moving all extremities, sensation intact, ambulatory with mild unsteadiness

 

ECG: Sinus tachycardia, TWI with ST depressions in V3-V6, II,III, and aVF, no ST elevations, low voltage in limb leads

VBG: 7.34/39.8/16.1/14/-3.9

Shock panel: 133/3.9/101/14/0.69<82

Labs:

 

Troponin <0.006

Lipase 27

TSH 2.6

UCG negative

UA negative

UTox negative

CSF no RBCs no WBCs

 

 

 

Imaging:

CT head: Negative

CT abdomen/pelvis: No acute intra-abdominal pathology. Multiple opacities in lower lung bases

 

ED Course: Patient was verbally undirectable and was given 5 mg of haloperidol and 2 mg of midazolam for sedation to continue evaluation and management. She received 3L of normal saline, ibuprofen, and was empirically covered with vancomycin, piperacillin/tazobactam, azithromycin, and acyclovir. She was admitted for severe sepsis likely due to multilobar pneumonia.

 

Inpatient Course:

Repeat troponin level to “rule out ACS” rose to 0.3 and cardiology was consulted. An initial transthoracic echocardiogram showed a normal ejection fraction. The next morning the patient became increasingly tachypneic with increased work of breathing. The ICU was consulted and the patient was intubated for airway protection. Pressors were required in the ICU and titrated to maintain a MAP of 65. Post-intubation, her P/F ratio was <300 but later dropped to 130. Repeat troponins continued to trend upwards to 6, and there was worsening ejection fraction to 35%. Given the moderate ARDS, cardiogenic shock, and overall deteriorating clinical status, the decision was made to transfer the patient to an outside hospital for extracorporeal membrane oxygenation (ECMO). She remained on veno-arterial (VA) ECMO for approximately 10 days before discontinuation, and she was extubated a few days after. Her inpatient course was complicated by lower extremity ischemia due to thrombosis distal to the femoral artery catheter site, which is a common complication. The patient later made a full recovery and was discharged home.

 

Basics of Extracorporeal Membrane Oxygenation (ECMO)

ECMO is a form of extracorporeal life support (ECLS) that involves the use of two catheters placed either into central veins or one into a central vein and one in the aorta to extract blood in order to oxygenate and remove carbon dioxide from the blood before returning it back into circulation. It will essentially do the work of the lungs or lungs and heart outside of the body. There are two main types of ECMO circuits. The first is VV-ECMO, which stands for veno-venous ECMO, denoting cannulation of two veins for input and output. VV-ECMO relies on the patient’s native cardiac output to deliver the blood oxygenated by ECMO back into circulation. This is why VV-ECMO is mainly used for respiratory failure. The second type is VA-ECMO, which stands for veno-arterial. VA-ECMO also replaces native cardiac function and is generally used as a form of cardiac bypass in addition to providing ventilation and oxygenation. Clinically, it is utilized for cardiac arrest or cardiogenic shock that complicates acute myocardial infarction. There is another form of less frequently used ECLS that only provides ventilation without oxygenation, known as extracorporeal carbon dioxide removal (ECCO2-R). This also comes in arterio-venous and veno-venous flavors.

 

The actual ECMO circuit can be conceptualized like the human circulatory system – there is a pump (heart), a membrane oxygenator (lung), heat exchanger, tubing (blood vessels), and cannulae (1). As with dialysis circuits, ECMO requires heparinization to prevent thrombosis.

 

Indications for ECMO

ECMO is generally reserved as rescue therapy for patients with reversible causes of cardiogenic shock, cardiac arrest, or ARDS (2). As per the Extracorporeal Life Support Organization (www.elso.org), indications for ECMO are (3):

 

“Acute severe heart or lung failure with high mortality risk despite optimal conventional therapy. ECLS is considered at 50% mortality risk, ECLS is indicated in most circumstances at 80% mortality risk. Severity of illness and mortality risk is measured as precisely as possible using measurements for the appropriate age group and organ failure.”

 

Contraindications for ECMO are relative and include:

• Conditions incompatible with normal life if there is recovery
• Preexisting conditions which affect quality of life:
  1. Poor baseline mental status
  2. End-stage malignancy
  3. Risk of systemic bleeding with anticoagulation
• Age and size of patient
• Futility: patients who are too sick, have been on conventional therapy for too long, or have a fatal diagnosis

 

Starting a patient on ECMO

The actual procedure of placing a patient on ECMO is similar to central venous/arterial access. There is an additional step of serial dilation in order to fit the large ECMO catheters into the blood vessels. The catheters are then connected directly to the ECMO machine. For more information, as well as fantastic videos and logistics on the procedure, follow the link below:

 

http://edecmo.org/logistics/ecpr/

 

Evidence for ECMO

Now that we know when it is indicated and how to do it, does it actually work? A Cochrane review in 2015 attempted to find the answer to that question and found that there was insufficient evidence to make any conclusions. They limited their search to randomized control trials (RCTs) and found only four studies in the last four decades. However, 2 of these studies were from the 1970’s when ECMO was still in its infancy, and 1 only used ECCO2-R for severe ARDS without lung-protective ventilation (2). Since then, the technology has become safer and more sophisticated (4). Unfortunately, the vast majority of ECMO clinical trials had severe methodological limitations. Firstly, it is impossible to blind providers or patients to the intervention. Secondly, there are ethical issues in consenting and randomizing patients to a potentially lifesaving therapy vs. conventional therapy. As a result, most studies were either a case series or cohort studies.

 

ARDS or Respiratory Failure

The CESAR trial, widely regarded as a landmark ECMO trial, was one of the few RCTs ever done on the therapy. It was a multicenter trial in the UK that randomized patients aged 18-65 with severe (defined by a pH < 7.2 or a Murray score >3.0 see http://cesar.lshtm.ac.uk/murrayscorecalculator.htm) but potentially reversible respiratory failure. They excluded patients with prolonged conventional ventilation with high oxygenation or peak pressures, intracranial bleeding or other contraindications to anticoagulation, or any other contraindications to continued treatment. They were able to randomize 90 patients to ECMO and 90 to the control group. There was a statistically significant difference in survival at 6 months without disability, with 57/90 (63%) ECMO patients meeting the outcome vs. 41/ 87 (47%) for the control group (5).

 

However, there was no true controlled treatment in the control group as the trial did not dictate a defined protocol of care for those patients other than the fact that they did not receive ECMO. Furthermore, 22 patients in the intervention group did not receive ECMO and 16/22 (72%) of these patients survived with conventional management but were included in the ECMO analysis. The remaining ECMO patients who did not receive ECMO either died before or during transfer or had a contraindication to heparin. The intervention group was also more likely to receive lung protective ventilation, steroids, albumin, or molecular albumin recirculating system (liver dialysis), making it difficult to tease out just how much ECMO contributed to the improved outcomes in that bundle of care (5).

 

Schmidt et. al in 2015 performed a rigorous review of the literature surrounding ECMO and respiratory failure. They noted that in the last 15 years, mortality ranged from 36-56% in studies of at least 30 ECMO patients. In the H1N1-associated ARDS studies, patients placed on ECMO had significantly higher survival. They found that the following were risk factors for poor outcomes on ECMO – older age, increasing number of days on mechanical ventilation prior to initiation of ECMO, multi-organ failure, low pre-ECMO respiratory system compliance, and immunosuppression (4).

 

Few studies have evaluated long term outcomes after ECMO for ARDS and generally report favorable or similar outcomes compared to conventional therapy in terms of respiratory function tests, quality of life, exertional dyspnea. However, a substantial number of survivors reported anxiety, depression, or PTSD.

 

Studies evaluating ECCO2-R in ARDS have been few and far between, and results from available literature have been disappointing, marred by small numbers, high mortality, or high rates of complications. One of the few positive studies, the Xtravent trial looked at ARDSnet ventilation vs. ultra lung-protective strategy with tidal volumes of 3 cc/kg using a pumpless ECCO2-R device. While there was no difference in ventilator free days at 60 days between groups, post hoc analysis found patients with P/F ratios <150 had significantly more ventilator free days at 28 and 60 days in the ECCO2-R group (4).

 

Cardiac Arrest and Cardiogenic Shock after AMI

The studies reviewed thus far have shown that ECMO may improve outcomes in patients with ARDS, but this has limited application in the Emergency Department. ECMO has also been studied as a component in extracorporeal cardiopulmonary resuscitation with important implications for the Emergency Department. A recent systematic review and meta-analysis by Ouweneel et. al looked at ECMO in cardiac arrest and cardiogenic shock after acute myocardial infarction. Survival in the meta-analysis was significantly improved over historical survival data for cardiac arrest. They included 13 studies encompassing 708 ECMO patients and found a NNT of 7.7 for 30-day survival with a NNT of 7.1 for favorable neurological outcome at 30 days in cardiac arrest, and a NNT of 13 for 30-day survival vs. intra-aortic balloon pump and no difference vs. TandemHeart/Impella. The studies evaluating ECMO vs. the ventricular assist devices (VAD), TandemHeart and Impella, were flawed in their design. The patients who were on placed on VAD’s were more stable with only left ventricular failure whereas the ECMO patients had biventricular or right ventricular failure. Long-term survival and survival with favorable neurological outcome favored ECLS patients with a NNT of 6.7 and a NNT of 9.1, respectively. This review suffered from significant heterogeneity between studies, making use of meta-analysis in this paper questionable. Interestingly, long-term survival data had less heterogeneity than short term outcomes, but there was still moderate heterogeneity with I² scores of 28%. The ECLS group had more males, was younger, had more acute myocardial infarctions, and thus more percutaneous coronary interventions further skewing results as these are factors may portend a better outcome. This review also does not specify which type of ECLS was studied, whether it was VV-ECMO or VA-ECMO (6).

 

Complications of ECMO

An invasive procedure like ECMO is not without its risks and complications. Owing to the large cannulation of central arteries and veins and the use of heparin to keep the circuit patent, thrombosis and hemorrhage are concerns with ECMO. A meta-analysis of studies that reported complications of VA-ECMO for refractory cardiogenic shock or cardiac arrest found composite rates of 10.7% for limb ischemia, 13.3% for neurological deficits, 47% for renal failure, 25% for infection, and 4.5% for thrombosis (7). Of note, the 22 studies included in this review had no control groups and were all observational cohorts with significant heterogeneity. While not discussed in this review, ECMO affects the pharmocokinetics of various drugs, by increasing volume of distribution and sequestering drugs within the circuit. If not properly accounted for, this can lead to increased complications from adverse drug events or from subtherapeutic drug levels (8,9).

 

Conclusions

ECMO presents one of the few advances in cardiac arrest, cardiogenic shock complicating acute myocardial infarction, and ARDS in the past few decades that demonstrates real promise. The positive effect on survival and favorable neurological outcomes suggested by the aforementioned studies may be legitimate; however, the studies are fraught with methodological problems. Once larger, reproducible studies are done, ECMO may well become the new standard of care for these critical conditions. Fortunately, the Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA) trial is currently underway, which should address most of the criticisms of the CESAR trial. It will look at early VV-ECMO in patients with severe ARDS with a well-defined protocol in the control group. All patients randomized to ECMO will receive the therapy. There is also a controlled, parallel group study enrolling in Canada that will look at ECMO and mechanical CPR for out of hospital cardiac arrest. These and future studies will hopefully put to rest the trepidation surrounding this potentially lifesaving intervention.

 

Back to our case, our patient had a P/F ratio suggestive of ARDS, but it was more likely secondary to cardiac dysfunction given the rising troponin and dropping EF. The patient likely had sepsis-induced cardiomyopathy vs. viral myocarditis. The data for ECMO does not focus on these disease entities, but given her critical illness with temporary etiology, she was deemed a good candidate for ECMO and fortunately made a full recovery.

 

TL;DR

The next time your cardiac arrest, cardiogenic shock, or ARDS patient tries to die on you, think, “HECK NO! ECMO!”

 

References

1. Suneesh Anand, Divya Jayakumar, Wilbert S. Aronow & Dipak Chandy. Role of extracorporeal membrane oxygenation in adult respiratory failure: an overview. Hospital Practice (2016). 44(2): 76-85.
2. Tramm R, Ilic D, Davies AR, Pellegrino VA, Romero L, Hodgson C. Extracorporeal membrane oxygenation for critically ill adults. Cochrane Database of Systematic Reviews 2015, Issue 1. Art. No.: CD010381. DOI: 10.1002/14651858.CD010381.pub2.
3. Extracorporeal Life Support Organization. ELSO Guidelines General_v1.3. elso.org. November 2013. Accessed October 14, 2016.
4. Schmidt M, Hodgson C, Combes A. Extracorporeal gas exchange for acute respiratory failure in adult patients: a systematic review. Critical Care. 2015;19(1):99.
5. Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D: Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009, 374:1351-1363.
6. Ouweneel, D.M., Schotborgh, J.V., Limpens, J. et al. Extracorporeal life support during cardiac arrest and cardiogenic shock: a systematic review and meta-analysis. Intensive Care Med (2016). doi:10.1007/s00134-016-4536-8
7. Xie A, Phan K, Tsai YC, Yan TD, Forrest P. Venoarterial extracorporeal membrane oxygenation for cardiogenic shock and cardiac arrest: A meta-analysis. J Cardiothorac Vasc Anesth. 2015;29(6):37–645
8. Shekar, Kiran et al. Pharmocokinetic changes in pateints receiving extracorporeal membrane oxygenation. Journal of Critical Care. Vol 27(6);741.e9-741.e18
9. http://lifeinthefastlane.com/ccc/pharmacokinetics-and-ecmo/

Figures

1. Suneesh Anand, Divya Jayakumar, Wilbert S. Aronow & Dipak Chandy. Role of extracorporeal membrane oxygenation in adult respiratory failure: an overview. Hospital Practice (2016). 44(2): 76-85.
2. Fanelli et. al. Acute respiratory distress syndrome: new definition, current and future therapeutic options. Journal of Thoracic Disease (2013). Jun;5(3):326-34.
3. http://www.irishnews.com/picturesarchive/irishnews/irishnews/2015/12/16/092411746-a13b4a73-24af-4a89-8284-a04eef58f73b.jpg