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Introduction
ECMO is a support modality that buys time. During that time, the patient can be treated. If the patient recovers, ECMO has provided a bridge to recovery. If treatment fails, or if no treatment is available and recovery is not expected, ECMO provides a bridge to further treatment or support. Patients with cardiac failure can be bridged to another device or to a heart transplant. Patients with respiratory failure can only be bridged to a lung transplant, as long-term support devices are not yet available.
Selection of patients who will ultimately benefit from ECMO is crucial to the success of a service. Failure to select patients who will either recover or be suitable for further therapies will cause a lot of suffering. Patients will remain for weeks in intensive care with no prospect of recovery. Staff will lose morale by having to care for futile patients. Managers will question the high cost when assessed against outcome.
Sadly, many patients are referred too late for consideration by the ECMO team. ECMO is not a miracle machine and cannot reverse the irreversible.
In the absence of clearly recognized criteria backed up by evidence, the clinician will often have to rely on expertise and experience. ECMO can kill even when patient selection is perfect, or can cause major harm with life-changing injuries. The good clinician will remain fearful, wondering if the timing of starting is absolutely right, as there are no definite indicators.
For all these reasons, most programmes require more than one person to be involved in making the decision to support or not.
Respiratory diseases
The clinician will face multiple factors when considering a patient with acute severe respiratory failure. Potential recovery will be obvious in many conditions, such as acute infection (e.g. Legionella pneumoniae, H1N1 influenza pneumonia, aspiration) or status asthmaticus.
An underlying respiratory condition may undermine the prospect of recovery, but this is not always easy to predict. A patient with mild emphysema may suffer a bad bout of flu and recover unscathed after a few days, while others might end up condemned to the ventilator for ever.
Co-morbidities, previously existing or newly acquired, will weigh in when deciding whether to go ahead or not. Constant progress and a team daring to challenge current clinical wisdom keep pushing the boundaries of what will be successful.
Too often, the underlying diagnosis is unknown when life or death decisions must be taken, and inevitably some conditions that appear to be reversible will prove ineluctable. Plans must be made for the patient, relatives and team to cope with this.
The chosen treatment and support modalities instituted because of or during ECMO may transform a potentially reversible condition into an irreversible one. Examples include mismanagement of mechanical ventilation or incorrect choice of antibiotics.
Reversibility
There is not yet a score that allows prediction with certitude of the recovery of any patient presenting with acute severe respiratory failure.
Patients presenting with acute infective pneumonia will usually recover if appropriate antibiotics and/or antiviral drugs are given early. Similarly, patients with acute severe asthma of allergic origin will recover if the trigger is removed. Patients with acute vasculitis or infiltrative disease of immune origin can recover if the diagnosis is made promptly and treatment given accordingly.
Immunosuppressed patients may not have the ability to fight the cause of the failure, and ECMO will not change the course of the disease. It is incredibly difficult to assess the immune system, and clinicians will be torn between the desire to try to save a life by gaining more time and the risk of potential harm.
Transplant centres are repeatedly reporting reversibility of acute rejection, justifying ECMO in immunosuppressed transplant patients presenting with this condition. This often requires great clinical acumen, as immunosuppression and other treatments have to be continuously adapted in this group of patients, balancing carefully the risk or spread of infection and the containment of rejection.
Patients with human immunodeficiency virus infection presenting with an acute severe respiratory failure should be considered. The CD4 cell count helps to predict outcome, but this is not absolute. However, patients with acquired immunodeficiency disease (AIDS; stage 4 of the disease) will most likely not have the immune reserve to control the pathological process.
Many lung diseases are not reversible, including lung fibrosis, emphysema, cystic fibrosis and chronic obstructive pulmonary disease. However, an acute infection may just be recoverable with the possibility that the patient’s condition will return to baseline or slightly worsen after ECMO support. The clinician will have to assess the impact of ‘slightly worse’ and weigh up the probability of a good outcome versus failure to recover.
Specific considerations
ECMO clinicians are eager to have clearly defined selection criteria. Selection criteria have been used in trials (such as the CESAR trial; see Table 5.1) and are used by many centres, such as the national respiratory ECMO service in England. These criteria are interpreted loosely as clinicians are confronted with previously healthy patients and encouraged by previous results.
| Inclusion |
| Reversibility |
| 18–65 years of age |
| Murray score (see Table 5.2) ≥3 |
| Non-compensated hypercapnia with pH <7.2 |
| Exclusion |
| Ventilated with fraction of inspired oxygen (FiO2) >80% or peak airway pressure >30 cmH2O for more than 7 days |
| Severe trauma within last 24 h, intracranial bleeding and any other contraindication to limited heparinization |
| Moribund and any contraindication to continuing active treatment |
Age is no longer recognized as an accurate indicator of outcome, and an index of frailty should be used. A reliable index of frailty has yet to be published (and is likely to include age but alongside other parameters).
The duration of ventilation is directly linked to the duration of support and outcome, but these vary from disease to disease and depend on co-morbid status. Waking and mobilizing patients on ECMO changes the duration of support and the ability to recover. A patient can be woken up while on ECMO and extubated, or can breathe through a tracheostomy. This allows mobilization and intensive rehabilitation, improving outcome and long-term recovery.
The Murray score gives an indication of disease severity but not necessarily of the chance of survival (Table 5.2).
The total score is attained by dividing the values obtained from the initial analysis by the number of elements used for the analysis. A score of zero indicates no lung injury. PaO2, partial pressure of O2 in arterial blood; FiO2, fraction of inspired oxygen; PEEP, positive end-expiratory pressure.
Patients with cerebral haemorrhage would not have been offered ECMO support a few years ago, and those developing cerebral haemorrhage while on support would have been palliated. This is now challenged, as new veno-venous circuits can be used for long periods (weeks) without anticoagulation and with minimum trauma to the blood. Many patients with an intracranial bleed have now been supported to full recovery. This extends to other causes of haemorrhage, and ECMO can be used in the trauma patient if the source of bleeding has been controlled.
Frailty
It may be paradoxical to claim that a patient has to be fit enough to survive the major insult leading to acute severe respiratory failure. The patient may indeed not be fit when presenting for ECMO. The physiological reserve will impact on how the patient will sustain the multiple insults linked to both support and treatment.
It is well recognized that modern medicine is increasingly treating older patients who benefit from multiple interventions or adjustments to maintain their health. Drugs given to control blood pressure and heart function may affect renal function but with no direct obvious impact until this finely tuned physiology is disturbed. Severe illness neuropathy or myopathy may lead to so much muscular loss that mobility becomes impaired leading to further problems. Scarring of lung tissue may result in an insufficient functioning lung volume and the inability to recover when the initial disease has been controlled.
Age in itself is not a definite indicator, but it is known that physiological reserve decreases with age. Registries have shown that a prolonged duration of ECMO support is needed in older patients, and poorer outcomes are reported for patients older than 65 years.
Patients requiring heavy nursing care in their day-to-day life will be poor candidates as they are unlikely to recover any autonomy. At best, they would return to their previous status, but sadly this is the exception.
The difficulty in assessing frailty, coupled with the progress made in supporting sicker patients, supports the importance of detailed history taking and physical assessment before starting support. The clinician will be eager that all patients who may benefit from ECMO will receive it, but will want to avoid causing unnecessary harm and inappropriate use of resources by commencing ECMO in some patients.
Obesity
Obesity was previously thought to negatively predict survival, but this has been disproven. While challenging for the ECMO team, morbidly obese patients can be supported with success. Limitations in care are usually due to other factors, such as unavailability of adequate transport equipment, the impossibility of entering a CT scanner and complications caused by physical difficulties mobilizing patients when in bed.
Brain injury
Brain injury is not a contraindication to ECMO, as long as recovery is expected.
Currently, veno-venous ECMO circuits can run for long periods of time without anticoagulation, and many patients with a cerebral haemorrhage have been supported to full recovery.
Duration of ventilation
Mechanical ventilation using positive pressure is detrimental to lung recovery. Studies have repeatedly shown that high-volume, high-pressure ventilation leads to poorer outcomes. The duration effect is well characterized, but one would logically infer that the longer it goes on, the worse it will be. Data also show that starting ECMO at a later stage leads to poorer outcomes.
Many guidelines suggest that patients should have been ventilated for fewer than 10 days to have a chance of recovery. However, they often mitigate such statements by adding that it is acceptable to take on patients ventilated for longer periods but at reasonable volumes and/or pressures.
One approach is to agree that fewer than 7 days of ventilation is acceptable. Any longer periods of time require estimation of the amount of lung that can be saved. This estimation is fraught with difficulties, and there are no defined rules to follow.
Failure of conventional management
It is a widespread misconception that a patient cannot be referred for ECMO before all other methods of conventional ventilation have been attempted. While ECMO carries an iatrogenic risk, it can only be beneficial if the patient can still be bridged to recovery or transplant. Delaying referral or commencement of ECMO to attempt another modality is not wise.
The CESAR trial, a randomized controlled ECMO trial in adult respiratory patients, showed that moving the patient to a centre providing ECMO was beneficial (although the study did not show that the survival of patients supported by ECMO was better). Transport of the patient is a difficult and dangerous time, and is better attempted before last ditch treatment has failed.
Irreversibility and lung transplantation
The question of reversibility is a moot point as patients whose lungs do not recover could be bridged to lung transplant. Issues arise immediately when this is evoked, as multiple conditions must be met:
The patient has to be eligible for lung transplant.
The patient will compete against other patients on the waiting list, and will need to be prioritized as they are using precious and expensive resources while on ECMO.
Organ availability means that long waiting times are often expected. This is compounded by the build-up of antibodies if transfused when on ECMO.
Data have shown that the outcomes of patients transplanted from ECMO are worse than those of patients who have been waiting at home. Many now argue that patient care while on ECMO has improved since these results were published, and patients awaiting transplant can now be woken up and receive intensive rehabilitation while on ECMO, improving fitness and increasing physiological reserve, in turn improving the chance of surviving the transplant operation.
Some centres have developed strategies by which they offer ECMO support to patients already on the waiting list and progressing to end-stage respiratory failure. Elective commencement of ECMO allows them to wait while awake, exercising and spending time with their family, albeit in the confines of an acute care environment. This concept is intriguing, as one has to be on the waiting list to be accepted, while others who are too fit to even be considered for lung transplantation will not be accepted for ECMO after an acute disease. Ethical dilemma and debate are a constant feature when offering ECMO to patients.
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