Therapy optimization before referring the patient for ECMO

• Ventilation according to lung protective strategy guidelines: VT≤6 mL kg-1 for the  predicted body weight (the ARDSNet table), maintenance of Pplateau <30 cm H2O, permissive hypercapnia if Pplateau > 30 (max.35) cm H2O, the pressure-controlled ventilation mode is recommended: PCV, BIPAP, BiLevel.

• Titration of PEEP to the optimal values of PaO2/FIO2, lung compliance within 5 – 15 - 20 cm H2O accounting for the effects on haemodynamics.

• A lung recruitment manoeuvre (LRM) every 4-8 h.

Two options:

1. PEEP 30 cm H2O for 20 sec, peak pressure to 40 cm H2O;

2. 2 x prolonged inspiration, up to 20 sec each, peak pressure 40 cm H2O – feasible by pressing the “inspiratory pause” button with which some types of ventilators are equipped. Monitoring of arterial pressure and saturation during LRMs.

• Thorough and frequent bronchial tree toilet (with the bronchofiberoscope, if possible). The LRM after each bronchial tree suction.

• The semi-recumbent position 30-45º, if possible.

• Adequate sedation. Everyday breaks in sedation to assess its required level. If need be, exceptionally, when multimodal sedation does not provide effective patient-ventilator synchronization - muscle relaxation. 

• Cautious consideration of steroid therapy: methylprednisolone 0.5-2.5 mg kg-1 a day over 7 days, particularly well grounded when histopathological findings in the transbronchial or thin-needle lung biopsy material indicate features of lung fibrosis. 

• Optimal fluid therapy, i.e. avoidance of fluid overload and aiming at dehydration of the patient, using kidney replacement therapy, if necessary. If extravascular lung water (EVLW) measurements are possible, its volume should be lower than 10 mL kg-1.

• Optimization of the cardiovascular system, invasive haemodynamic monitoring in cases of haemodynamic instability (thermodilution monitoring of cardiac output may be considered).

• Assessment of ventilation effectiveness in the prone position - if PaO2/FIO2 significantly improves -> the prone position should be used for at least 2x6 h a day-1.

• Assessment of efficacy of advanced ventilation techniques (if possible): PCV, IRV, APRV, oscillation ventilation, individual lung ventilation (independent lung ventilation).

• In the centres with suitable devices, optimization of oxygenation using inhalation therapy with nitric oxide (NO) or prostacyclin (e.g. Iloprost) delivered by nebulization may be attempted.

• The application of techniques limiting the risk of VAP, i.e. rational antibiotic therapy, avoidance of reintubation, intubation and gastric probes through the mouth, body position, suction from above the endotracheal tube cuff, everyday breaks in sedation, enteral feeding as soon as possible, control of blood glucose, prophylactic measures to prevent ulcer disease and deep vein thrombosis.

• It should be explicitly stressed that the method of lung ventilation chosen should also be applied during transportation of the patient to other centres for diagnostic or surgical procedures. The lung ventilation methods chosen are conditioned by availability of high-quality transport ventilators equipped with suitable oxygen reserves.

Monitoring and examinations of the patient prior to referral for ECMO

Basic examinations:

• Pulsoxymetr.

• Acid-base balance of the arterial blood – at least 1x3 h.

• Direct measurements of arterial pressure.

• Measurements of central venous pressure.

• Renal function parameters.

• Markers of cardiac necrosis.

• Ventilation parameters including: VT, f, FIO2, PIP, static lung compliance.

• PEEP – at least once an hour.

• Chest radiographs.

• Lung computed tomography should be considered the basic radiological method of their imaging.

Additional examinations (if available):

• Blood lactate concentration.

• Echocardiography.

• If the AH1N1 infection is suspected, the PCR method should be usedfor confirmation.

Medical criteria for ECMO treatment of acute respiratory failure in anaesthesiology and intensive therapy as well as cardiac anaesthesiology units

ECMO therapy is indicated for respiratory or cardiac-respiratory  failure, in which, despite high concentrations of oxygen delivered, methods of advanced ventilator therapy applied and optimization of the patient`s status, persistent hypoxaemia and hypercapnia pose the risk of further deterioration leading to death.

While qualifying for ECMO therapy, the direction of changes in gas exchange parameters following the use of advanced methods of ventilator therapy and optimization of the general status of the patient should be considered, bearing in mind that delayed onset of ECMO reduces the survival chances.

The main criterion:

• PaO2/FIO2<70 mm Hg, at PEEP≥10 cm H2O, which does not increase for at least 2 h despite the optimal (described earlier) respiratory therapy.

Auxiliary criteria:

• pH < 7.2, PaCO2 > 80 mm Hg.

• Static compliance < 0.5 mL kg-1 cm H20-1.

• PIP>40 cm H2O, at VT ≤6 mL kg-1.

• Oxygenation index: OI=(MAP x FIO2 x 100)/ PaO2 > 60 mm Hg for 30 min or  > 35 mm Hg for 6 h (MAP – Mean Airway Pressure).

• Chest X-ray: extensive shadows in at least two pulmonary quadrants.

Alternatively:

• The Murray lung injury score (LIS ) > 3.0.

• To assess the severity of patient`s status, the SOFA should be used twice a day. The SOFA score, however, is not an inclusion or exclusion criterion for ECMO.

Contraindications for ECMO therapy

• Severe systemic disease.

• Substantial immunosuppression.

• Intracranial haemorrhage and other contraindications for heparinization.

• Earlier artificial ventilation for > 7-10 days, particularly when lung protective strategy criteria could not be met.

• An irreversible pathological process in the lungs or other organs.

• Lack of patient`s consent.

• Age >65 years.

Therapeutic management during ECMO therapy

• Proper gas pressures in the arterial blood are obtained mainly due to gas exchange in the ECMO oxygenator. The ventilation of lungs is only supplementary and should be administered to ensure their regeneration as soon as possible.

• The basic measure to treat acute respiratory failure with uncontrollable hypoxaemia, despite the advanced methods of ventilator therapy used, is venous-venous ECMO. If marked circulatory failure coexists, in most cases it results from hypoxaemia, thus the function of the circulatory system improves quickly once proper blood oxygenation is restored. 

• In special cases, venous-arterial ECMO should be considered (in patients with cardiac failure in the course of endocarditis, history of severe circulatory disease or markedly increased markers of cardiac necrosis), if large doses of catecholamines are needed to support the circulation.

• The fresh gas flow is adjusted to current PaCO2 values, increasing it in hypercapnia and decreasing when PaCO2 is too high.

• The blood flow in the centrifugal pump is adjusted to obtain optimal oxygenation of arterial blood (range 100-150 mm Hg). An increase in blood flow through the oxygenator increases the oxygen pressure whereas a decrease results in its reduction.

• If limited venous flow does not provide minimal oxygenation (about 70 mm  Hg), the position of the cannula should be corrected or placement of an additional cannula considered.

• During ECMO therapy, lung ventilation should be sparing: PIP 20 cm H2O, f 10 min-1, PEEP 10 cm H2O, FIO2 0.3.

• The heparin-coated kits are beneficial [1].

• To prevent blood clotting in the extracorporeal circulation, anticoagulation is necessary using the continuous infusion of non-fractionated heparin in the doses suitable to maintain the activated clotting time (ACT) within the range of 160 s - 200 s.

• During ECMO therapy, platelet counts should be kept above 100 000 mm-3.

• Whenever possible, invasive procedures should be avoided to reduce the risk of haemorrhage. Tracheostomy should be carried out before ECMO is initiated, if possible [1, 2].

• The haemoglobin concentration should be maintained above 13 g dL-1.

• During therapy, the negative fluid balance should be obtained yet proper tissue perfusion maintained.

• In the first days of therapy, deep sedation should be continued. During further therapy, sedation ought to be reduced to enable lung pressure support ventilation (PSV).

• If parenteral feeding or renal replacement therapy is required, they should be directly connected to the ECMO circuit to reduce the risk of complications related to central venous cannulation.

• No effort should be spared to prevent hypothermia.

Monitoring during ECMO therapy

Basic monitoring:

• Pulsoxymetry.

• Acid –base balance of the arterial blood – at least every  3 h.

• Direct arterial pressure measurements.

• Measurements of central venous pressure and their interpretation are of a limited value due to active blood suction by the centrifugal pump.

• Renal function parameters

• Ventilation parameters: VT, f, FIO2, PIP, static lung compliance, PEEP – recorded at least 2 times a day

• Lactate concentrations.

• ACT or APTT – every 6 h.

• INR, PTT, D-Dimers, fibrinogen, AT-III, platelet count – 1x day.

• Chest X-ray – at least every 3 days.

• The device-related parameters should be recorded every hour: blood flow, number of pump rotations, pre- and post-oxygenator pressures. Increased pressure gradients in the oxygenator and decreased blood oxygenation at constant flow indicate its “wear” or higher risks of coagulation. The replacement of the oxygenator or the entire extracorporeal circulation circuit should be available, if need be.

Additional monitoring (whenever possible):

• Echocardiography (1 x a day) to assess the heart function and position of the cannula.

• PICCO – assessment of extravascular water volume in the lungs.

• CT of the chest, abdominal cavity, head – according to clinical indications.

Technical problems and complications related to ECMO therapy

a. Patient-related complications:

• Haemorrhage (including heart tamponade and pleural haemotoma).

• Infection.

• Embolic complications.

• Neurological complications.

• Organ failure (kidney, heart, liver).

• Barotrauma.

• Metabolic abnormalities.

b. ECMO device- and circuit- related complications and problems:

• Sequels to faulty deareation of the circuit.

• Displacement or removal of the cannula.

• Oxygenator malfunction (wear, clotting).

• Circuit failure (disconnection, damage).

• Heater-cooler malfunction.

• Pump malfunction.

• Atrium perforation by the cannula.

c.    Management in cases of some technical problems:
Irrespective of the its mechanism, each malfunction of the device poses direct threat to patient`s life and requires immediate changes in ventilator parameters to ensure sufficient gas exchange in the lungs and fixing the technical problem as soon as possible.

• Disconnection or leak of the circuit, cannula removal -> immediate cannula clamping,  calling for a cardiac surgeon and perfusionist.

• Pump malfunction, flow drop, temporary flow decreases -> calling for a cardiac surgeon, correction of cannula position, increase in vascular bed filling.

• Oxygenator clotting -> calling for a cardiac surgeon and perfusionist. Change of the oxygenator or the entire circuit.

• Presence of thrombi in the dome or other part of the circuit -> calling for a cardiac surgeon and perfusionist. The replacement of the dome or the entire circuit.

• Reduced body temperature -> calling for a perfusionist, checking the heater-cooler.

• Flow arrest in venous-arterial ECMO -> cannula clamping. Calling for a cardiac surgeon and perfusionist. Assessment of the patient`s condition to initiate cardiopulmonary resuscitation.

• In cases of venous-arterial ECMO, it should be remembered that the centrifugal pump is an non-occlusive pump and its stoppage causes immediate flow from the arterial to venous cannula; therefore, cannula clamping is essential until proper pump functioning is restored.

• The mean time to non-heparinized oxygenator change is about 5-6 days; however, the device may function much longer without any replacements of the device, centrifugal pump dome and cannula.

Discontinuation of ECMO therapy

• An extensive ischaemic focus in the brain.

• Massive intracranial haemorrhage.

• Diagnosis of other incurable diseases during therapy.

• No chances to improve the respiratory function despite long-term therapy.

Weaning from ECMO

a. Conditions:

• Subsidence of X-ray-detected lung changes.

• Improved oxygenation of arterial blood at FIO2<0.6 and improved lung compliance (PIP < 30 cm H2O) during attempts to reduce ECMO support.

b. Attempted reduction of ECMO support to assess its possible discontinuation:

• Reduction of support during venous-venous ECMO: the flow reduced to 1 L min-1 and closure of fresh gas flow to the oxygenator for at least 2 h.

• Reduction of support during venous-arterial ECMO: the flow reduced to 0.5 L min-1 for at least 6 h.

• During the reduction of centrifugal pump flow below 2 L min-1, adequate heparinization is essential.

• Maintained adequate gas exchange parameters during reduction of venous-venous support and haemodynamic parameters during venous-arterial support indicate possible safe disconnection of ECMO. In each case, the decision should be made with caution and the entire clinical condition considered.

The ECMO therapy team

ECMO therapy should be performed in close cooperation of specialists in anaesthesiology and intensive therapy, cardiac surgeons, intensive therapy nurses and perfusionists. Their cooperation should be based on the following assumptions:

• Anaesthesiologists and intensivists familiarized with ECMO therapy available 24 h  day-1.

• A surgeon familiarized with ECMO therapy and details concerning the device operation is on standby for 24 h day-1 (e.g. a physician on duty in the cardiac surgery department).

• Intensive therapy nurses familiar with the ECMO therapy principles and operational details deliver direct patient care.

• A perfusionist – checking the device function at least 1 x a day is on standby for 24h day-1.

Suggested organization of therapy

• Patients requiring ECMO therapy are referred to by the head of the ITU or his/her deputy.

• The referring physician is obliged to verify the therapy accordance with the recommendations mentioned earlier, particularly appropriate ventilator therapy. 

• Possible institution of ECMO in the referring centre unit should be considered if PaO2<60 mm Hg at FIO2 = 1 and PEEP≥10 cm H2O.

• If there are no vacancies in the regional accredited ECMO centre, the patient should be referred to the nearest centre.

• Once acute kidney failure develops, the patient should be referred to the centre where kidney replacement therapy is available.

• The referring unit pledges to admit the patient for further treatment after ECMO discontinuation and once the respiratory and circulatory functions have been stabilized enough to ensure safe transport.

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REFERENCES

1.    Peek GJ, Moore HM, Moore N, Sosnowski AW, Firmin RK: Extracorporeal membrane oxygenation for adult respiratory care. Chest 1997; 112: 759-64.

2.    Linden  V, Palmer K, Reinhard J, Westman R, Ehren H,Granholm T, Frenckner B: High survival in adult patients with acute respiratory distress syndrome treated with extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation. Intensive Care Med 2000; 26: 1630-1637.

3.    Murray JF: An expanded definition of the adult respiratory distress syndrome. Am Rev Resp Dis 1988; 138: 720-723.

4.    Lewandowski K: Extracorporeal membrane oxygenation for severe acute respiratory failure. Crit Care 2000; 4: 156-166.

5.    The Australian and New Zealand Extracxorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA 2009; 302: 1888-1895.

6.    Neapolitano LM: Intensive care patients with severe novel influenza A(H1N1) virus infection – Michigan, June 2009; MMWR Weekly 2009; 58(27): 749-752.

7.    Pranikoff T, Hirschl RB, Steimie CN, Andersen HL: Mortality directly related to the duration of mechanical ventilation before the initiation of extracorporeal life support for severe respiratory failure. Crit Care Med 1997; 25: 28.

8.    Hemmila MR, Rowe S, Boules TN, Miskulin J, McGillicuddy JW, Schuerer DJ, Haft JW, Swaniker F, Arbabi S, Hirscjl RB, Bartlett RH: Extracorporeal life support for severe acute respiratory distress syndrome in adults. Ann of Surg 2004; 240: 595-607.

9.    Peek GJ, Mugford M :For the CESAR trial collaboration: Efficacy and economic assessment of conventional ventilator support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicenter randomized trial. Lancet online 2009, www.sciencedirect.com/science/journal/140-6736(09).

10.    Joseph B Zwischenberger, James E: Will CESAR answer the adult ECMO debate? Lancet online 2009, www.sciencedirect.com/science/journal/140-6736(09)61630-61635.

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Address:

*Romuald Lango

Zakład Kardioanestezjologii UM w Gdańsku
ul. Dębinki 7, 80-211 Gdańsk
tel.: (0-58) 349 24 83
e-mail: rlango@gumed.edu.pl

Received: 07.12.2009
Accepted: 30.12.2009