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Neonatal Post Cardiotomy Cardiac Assistance.

Clarke Thuys, BAppSc, GradDipAppSc, CCP (Aust)

Victorian Paediatric Cardiac Surgical Unit
Royal Children's Hospital
Melbourne, Victoria
Australia

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The most common technique used in Cardiac Surgery centres around the world for post cardiotomy support in infants and children is Extra Corporeal Membrane Oxygenation (ECMO). There is now considerable evidence to support its use in this role. Conversely the experience with Ventricular Assist Devices (VAD) in neonates and children is, to date, relatively small, primarily due to technical factors and concerns regarding suitability of these patients for univentricular support.

Some patients will present with a pre-op diagnosis of having poor ventricular function, and may be more likely candidates for post-op support. Others will have suffered a myocardial insult during surgery resulting in a hypoxic ischaemic myocardium that is unable to perform adequately. The cause of the injury was initially ascribed to imbalances between myocardial energy supply and demand, but the aetiology is far more complex. Toxic oxygen-free radicals are now recognised as a cause of damage to multiple sites within the heart. A reduced cardiac output will also affect other organs in the body due to the low blood pressures and blood flow of a failing heart. Over a period of time allowing the myocardium to rest may reverse this damage.

Patients with congenital heart lesions will have varying intra-cardiac blood flow patterns, which results in a mix of saturated and desaturated blood. As a result of this, myocardial blood supply is usually compromised further by forward output limitations or by virtue of receiving desaturated blood. Patients with anomalous origin of the left coronary artery (ALCAPA) may have evidence of ischaemic myocardial damage at the time of diagnosis and are most vulnerable to further insult. Patients with hypoplastic left heart syndrome (HLHS) will have poor forward output through the aorta. The coronary perfusion will be marginal unless there is adequate perfusion via the patent ductus arteriosus (PDA). Perfusion via the ductus may be maintained pre-operatively using Prostaglandin (PGE 1). Cannulation of the aorta for CBP may also compromise the coronary blood flow.

Certain congenital cardiac lesions are severe enough to warrant correction in the first few days or weeks of life. The myocardium is immature because certain biological changes have been delayed by the physiological alterations that result from the congenital defect. Results from mainly animal studies show that there are fewer contractile elements in neonatal myocardium compared to adult myocardium and that in neonates these elements are not as well organised. Also the mitochondria are not as closely related to the contractile elements. Other differences include a reduced sarcoplasmic reticulum population and a poorly developed T-tubule system. The immature myocardium is more dependent upon calcium flux for contraction. It is unable to increase output in response to increases in preload but exhibits dramatic decreases in output with reduction in preload. Afterload increases are poorly tolerated and sudden increases result in decreased cardiac output.

Immature versus Adult Myocardium

IMMATURE VERSUS ADULT MYOCARDIUM
IMMATURE	ADULT
1. Few contractile elements	Many contractile elements
2. Fewer mitochondrial rows along contractile elements	Mitochondrial form rows along contractile elements
3. Reduced sarcoplasmic reticulum	Abundant sarcoplasmic reticulum
4. Poorly formed T-tubules	Well formed T-tubules
5. Lower myofibrillar ATPase activity	Normal myofibrillar ATPase activity
6. More potential for glycolitic ATP generation (tolerates anoxia better)	Oxidative metabolism
7. Decreased developed tension	Normal developed tension
8. Decreased output with increasing preload	Able to maintain output with increase in preload
9. Ca2+ for excitation-contraction coupling transsarcolemmel	Ca2+ for excitation-contraction coupling sarcoplasmic reticulum

The rate of ATP hydrolysis by the myofilaments is reduced which accounts for the reduced force generation capability. Mechanical performance could also be limited by a potential restriction of high-energy phosphate availability during periods of high demand.

Another group of patients at risk are those with hypertrophic lesions. Subendocardial flow is frequently marginal and may be reduced to inadequate levels during the pre-bypass period if low perfusion periods occur.

Patients with myocardial failure may be at higher risk for further intra-operative failure due to a low output associated with higher filling pressures that reduce subendocardial perfusion. Usually the heart is abnormal biochemically. Calcium transports are impaired, the contractile apparatus cannot generate normal force-velocity relationships and energy shuttling within the cell is compromised. Intra-operative injury invariably involves the calcium transport mechanisms. This can result in total ventricular failure if significant damage occurs to these already suboptimal systems.

The heart is more vulnerable to myocardial injury during:

1. The pre-bypass period due to inadequate perfusion.
2. A beating empty heart associated with a low blood pressure.
3. Hypothermia with reduced perfusion pressure and an induced tachycardia.
4. Cross clamping of the aorta if fibrillation occurs.
5. Long periods of cross clamping associated with consumption of high-energy phosphates even though no work is being done.
6. Reperfusion injury.
7. Troublesome arrhythmias.

During the pre-bypass period most injury is a result of inadequate perfusion. Hypoxaemia alone will not cause injury to the neonate or cyanotic heart as long as substrate is provided and metabolic byproducts are removed. If there is reduction in substrate availability and a decrease in washout of toxic byproducts, injury will occur. Ischaemia is capable of causing irreversible damage if allowed to persist. Periods of ischaemia shorter than those that produce irreversible damage may predispose the heart to reperfusion related damage.

Postoperative circulatory support constitutes the most frequent paediatric indication for both ECMO (as circulatory support) and VAD. The majority of patients will have undergone reparative open heart procedures or transplantation and are unable to be separated from CPB due to severe ventricular dysfunction. A subset will require support for low cardiac output in ICU following successful weaning from CPB. In either case, primary failure of the procedure will have been ruled out, as much as is possible under the circumstances. The aim is recovery of myocardial function, usually within 10 days, and eventual separation from ECLS, although bridge to transplant remains an option for selected patients.

Contraindications for ECLS include multiple organ system failure, severe coagulopathy, intracranial haemorrhage, neurologic impairment and sepsis. These criteria are relative rather than absolute, and are often not diagnosable intraoperatively. It could be said that most children who are candidates for cardiac surgery are candidates for ECLS if the need arose. Prolonged cardiac arrest (up to 1 hour) has not precluded successful outcome, providing CPR has been adequate.

For patients who cannot be weaned from cardiopulmonary bypass a decision is made whether to use any extracorporeal support. This question relates to the technical adequacy of the procedure and whether anything further can be done surgically. Trans-oesophageal echo, direct chamber pressure measurements and mixed venous oxygen saturation levels can provide important information. Assuming the procedure has been adequate an assessment of potential for recovery of ventricular function can be made based upon pre-operative condition and underlying anatomy.

The next decision involves the type of support: VAD or ECMO? Patients with isolated ventricular dysfunction can usually be supported by VAD. For some patients it is clear that univentricular support with a VAD will not be adequate. For example when global RV and LV failure are present. The same may be said for patients with severe pulmonary hypertension or pulmonary dysfunction complicating the picture. It should be borne in mind however that the decrease in left atrial pressure usually seen with LVAD might dramatically improve pulmonary hypertension and right ventricular dysfunction in borderline cases, especially with the concurrent use of nitric oxide. Right ventricular function is sensitive to left ventricular function in a number of ways. By unloading the left ventricle with VAD, right ventricular filling is improved and the decrease in chamber size and septal shift may improve tricuspid valve function as well.

Inhaled nitric oxide is an effective and inexpensive treatment for pulmonary hypertension. It is also useful for the support of the right heart during low cardiac output states requiring support with LVAD. Even if pulmonary artery pressure is normal some patients may benefit haemodynamically with improved left atrial filling. A secondary benefit may be an improvement in ventilation/perfusion mismatch in selected patients with pulmonary dysfunction.

While the patient is still on CPB, ventricular and pulmonary functions are evaluated. A left atrial cannula is inserted (using a Y connector) to the venous line of the CPB circuit. The right atrial cannula is clamped and blood from the left atrium drains by gravity into the venous reservoir of the oxygenator. In patients with univentricular anatomy no cannula changes are necessary. Ventilation, provided by the anaesthetist is increased to appropriate levels and the sweep gas to the oxygenator is turned off.

While on VAD using the CBP circuit right ventricular function and pulmonary artery pressures can be observed. At full flow, good contraction of the right ventricle and an appropriate right atrial pressure (without pulmonary hypertension or right heart distention) indicate that right heart function may be adequate to allow the use of ECLS without an oxygenator. Serial blood gases are analysed to evaluate lung function. If oxygenation, CO2 clearance and lung compliance remain in an acceptable range over 15-20 minutes the patient is deemed suitable for LVAD. If either right ventricular or pulmonary function is inadequate, then ECMO may be required.

The circuit consists of a centrifugal pump head, flow probe, PVC tubing, connectors, taps, aortic and venous cannulae, and pump inlet and outlet pressure monitoring lines (see diagram). All or some of these components may be heparin bonded. We use CPB cannulae designed to carry 150ml/kg/min flow.

The pump remote head drive is mounted on either the heart lung machine (HLM) or a drip stand, at patient height, as close to the patient as practicable. The flow probe should be kept near to the remote head and ready to connect to the transducer.

The circuit (possibly pre-assembled) is opened onto the surgical field and primed from the CPB circuit via a luer lock connector and tap already on the aortic cannula. The CPB flow may need to be temporarily increased to facilitate filling the VAD circuit. Once filled the circuit is de-aired. Excess blood is returned to the bypass circuit using a sucker. The two open ends of the VAD circuit are then clamped approximately 2 cm from the ends, and the priming line is removed.

If VAD is initiated in ICU the patient requires a loading dose of Heparin (1 mg/kg) prior to cannulation.

In ICU the circuit is primed using a 50 ml syringe with Plasmalyte 184, or possibly in combination with donor blood. It is then de-aired and clamped at both ends.

Diagram 1. VAD Circuit.

To initiate VAD, bypass is stopped and the aortic and venous cannulae are double clamped. The CPB cannulae are then removed from the CPB circuit between the double clamps. Luer lock connectors with taps are included in the VAD circuit pack. The pump inlet and outlet of the circuit are then connected to the appropriate cannulae. The circuit is de-aired, using a syringe on the Luer lock connectors.

Both sides of the circuit must be free of air before VAD flow is started. The flow transducer should be zeroed and connected to the flow probe in the correct orientation before flow is commenced.

VAD support is commenced at minimal flow and increased to a predetermined flow rate, usually 70% of the calculated CPB flow rate. In univentricular VAD this might be up to 150% of full CPB flow, to allow for lung perfusion via the aorta pulmonary shunt.

A pressure monitoring line is attached to the tap on the Luer connector of the pump inlet tubing and the other end is handed out to the perfusionist who connects it to a monitoring line with an isolator fitted. This line and its transducer isolator must be filled with heparinised normal saline, (1 unit per ml), using a 50 ml syringe on the isolator, and completely de-aired. It is then connected to the pressure transducer situated in the pump console.

The pump inlet pressure monitoring line should be turned off to the patient and open to air to zero the transducer. Flush the line from the syringe on the transducer isolator, and then zero the transducer using the control inside the console. When the pressure display on the console reads zero, recap the tap. Ensure that the pressure monitoring line is connected through to the transducer, not the flush syringe. Turn the tap on the luer connector so that the pump inlet pressure is being monitored.

Measuring the pump inlet pressure enables patient volume status and venous cannula placement to be monitored. VAD pump outlet pressure is set up and monitored in the same way except that a standard disposable pressure transducer is used, connected to the theatre or ICU monitoring system. Measuring pump outlet pressure allows changes in arterial resistance and aortic cannula placement to be monitored.

Once the patient is stable on VAD support, the heparin is reversed with protamine. An activated clotting time (ACT) of 130 - 140 seconds (using a Medtronic 'Hemotech' ) is required and surgical haemostasis is secured. Following surgical haemostasis the skin is closed with the cannulae exiting at either pole of the incision.

Despite differences in bed sizes the same basic technique is used to move the patient from the operating table to the bed. Wherever possible a VAD base plate and pole should be used to secure the remote pump head to the bed. The procedure requires a minimum of 5 people. One person is required to hold the remote pump head and flow probe. One person is required to ensure that the cannulae are secure during the move. Another should watch the flow and pressure readings on the pump console. The haemodynamic pressure monitoring transducers need to be detached from the operating table as do the drains, urine bag, heating mattress lines and anything else connected to the table. The patient is then lifted by an appropriate number of people. The operating table is slid away from underneath and the bed is moved into position under the patient who is then lowered onto it. The VAD base plate pole is secured in the base plate with the remote head and flow probe holder clamped to the pole in a position which ensures that the circuit will not kink. This maneuver may result in some change in VAD flow and pump inlet pressure. Small changes in patient position on the bed may be necessary to permit optimum flow and pump inlet pressure.

Once the syringe pumps, drains etc. have been attached to the bed, the patient is ready for transportation to ICU. It is easiest for the VAD trolley to follow behind the bed. Someone should be positioned between the VAD trolley and the bed to ensure that the remote head drive cable does not get caught up anywhere and that the pump inlet pressure monitoring line does not disconnect or put undue stress on the venous cannula.

On arrival in ICU move the pump console into a position close to the bed and plug it into mains power, lock the wheels. Regular haemodynamic pressures, ECG and saturation monitoring should be restarted as soon as possible. Secure the circuit to the bed making sure that the tubing will not kink.

Handover to the nursing staff must include:

1. Required flow rate.
2. Expected pump inlet pressure at that flow.
3. Minimum and maximum acceptable flow rates.
4. Maximum acceptable pump inlet pressure.
5. ACT requirements.
5. Cannula sizes and position.
6. A brief description on how the VAD has run until transport to ICU.

The pump inlet pressure transducer should be rezeroed if needed. ACT should be measured. This data is all recorded on the VAD record sheet.

The patient is kept sedated and paralysed with full mechanical ventilation. Anticoagulation is managed with a heparin infusion titrated to an ACT of 140 - 160 seconds. The recommended Heparin starting dose is 20 u/kg/hr. Inotropic support is reduced to the minimum level required to support the non VAD side of the heart. Normothermia is maintained. The circuit may need to be wrapped in aluminium foil to reduce heat loss through the circuit tubing.

Hourly records of arterial pressure, pump inlet pressure, pump outlet pressure, left atrial pressure, right atrial pressure, pump flow, pump RPMs, ACT and heparin infusion rate are recorded in the VAD record.

Patients may receive antibiotics, parenteral nutrition, and periodic fresh frozen plasma (FFP) and platelet infusions as required to maintain haemostasis. The heparin infusion rate is increased by 10% while platelets are infused. Renal support, if necessary, is provided by peritoneal dialysis.

Daily plasma haemoglobin measurements are taken, and if the level rises to above 0.60 mg/l, consideration is given to changing the pump head, if thought to be the cause of increasing haemolysis.

Both nurses inspect the circuit for clots at each change of nursing shift. The pump head is auscultated to determine if clots are forming on the cones or bearings. Observations are noted in the VAD record.

Patients are generally supported on VAD for a minimum of 24 hours, unless complications arise, before any assessment of ability to wean from support is made. After 24 hours the VAD flow rate may be reduced to allow some ventricular ejection at a left atrial pressure of 8 - 10 mmHg. Using echocardiographic guidance, increased fractional shortening and a positive Starling response to a reduced degree of VAD support are considered to be indications of myocardial recovery.

If the haemodynamics remain stable over a period of a few hours the flow rate might be reduced again, otherwise it is returned to its previous rate. This procedure is continued until the patient is haemodynamically stable on a minimal flow rate (approximately 200 ml/min).

It is possible to cease support and leave the cannulae in situ with the circuit tubing clamped for short periods of time. For periods of more than 4 or 5 minutes a heparinised saline solution (5 units/ml) can be flushed continuously at a rate of 5 ml/hour through the taps on the cannulae.

Decannulation can be performed in ICU or theatre. Decreasing the VAD flow rate to virtually no flow precedes decannulation. At this point in time the surgeons clamp the cannulae and remove them in the same manner as for removal of cannulae after CPB.

VAD for biventricular support is also possible. The right atrium and main pulmonary artery can be cannulated in the same way as the left atrium and ascending aorta for LVAD. Two pumps, with the RVAD pump running at 70% to 90% flow of the LVAD pump flow, are used. A competent pulmonary valve is necessary for BiVAD support.

Is VAD possible in patients with univentricular circulation? This is currently a point of controversy, but my unit and others have successfully supported patients with VAD after the Norwood operation for hypoplastic left heart syndrome as well as after bi-directional cavopulmonary shunts performed as part of other complex univentricular variants. Cannulating the right (or common) atrium and the ascending aorta provides support. In such cases, higher than normal flows (~ 1.5 x calculated) may be required, as the assist device provides both systemic and pulmonary output. In our own practice, Blalock shunts have been left open during VAD (as well as ECMO) support.

1. Accidental Decannulation

Arterial Decannulation (complete or partial).
Indications: 1. Decreased blood pressure.
2. Increased blood in chest drains.
3. Clinical signs of tamponade.

Venous Decannulation.
Indications: 1. Air in circuit tubing.
2. No pump flow.
3. Increasingly negative pump inlet pressure.

Management.

1. Clamp arterial and venous circuit tubing and turn pump off.
2. Put the patient head down (Trendelenburg position) if air is suspected to be in the aortic cannula.
3. Call the surgeons, ICU consultants etc.
4. Administer volume if necessary.
5. Increase inotropic support and perform cardiac massage if required.
6. Prepare for chest opening.

2. Air in Venous Line or Pump Head

Management.

1. Clamp both cannulae.
2. Turn the pump off.
3. Maintain cardiac output.
4. Attach a 50 ml Luer lock syringe to the tap on the venous cannula.
5. Disconnect the pump head from the remote drive unit.
6. Holding the pump head lower than the cannula, shake and tap the circuit to move the air up towards the 50 ml syringe.
7. Aspirate with the syringe until all the air is removed.
8. Remove the syringe ensuring the tap is turned the correct way.
9. Re-attach the pump head to the remote drive.
10. Reinstitute VAD. Remove the venous clamp, increase the pump speed to 700 rpm, remove the arterial clamp and increase the pump flow to the required level.

3. Air in Arterial Line and Patient.

1. Clamp the arterial and venous lines, not the cannulae. Turn the pump off.
2. Find out from where the air came.
3. Put the patient head down (Trendelenburg position).
4. Call the cardiac surgeon, ICU consultant etc.
5. Maintain cardiac output.
6. Have plenty of filling available and someone to administer it.
7. Attach a 50 ml luer lock syringe to the 3 way tap on the connector between the circuit and the arterial cannula and open the tap.
8. If air is seen in the arterial cannula, aspirate blood to remove any air sitting in the cannula. Clamp the cannula once the air is removed.
9. Remove the clamp from the arterial circuit line and tap the tubing to move the air towards the syringe. Aspirate the air from the circuit. Fill the patient as required.
10. If no more air is seen reinstitute VAD.

4. Pump Head Failure. A). Crack inside plastic head.
Cause: a) contact with alcohol.
(rough surface will cause hemolysis).

B). Blood leak from Pump.
Cause: a) as above
b) pump split.
Procedures:
a) Clamp arterial and venous lines.
b) Ventilate patient and maintain cardiac output.
c) Replace any volume lost.

PUMP HEAD CHANGE:

Equipment required:
a) Pump head.
b) Fluid administration set.
c) Betadine solution, sterile scissors, gloves, gown, and towels.
d) Tubing clamps.
e) 50 ml syringe filled with 5 % Glucose or normal saline.

Procedure
a) Put on hat, safety glasses and mask.
b) Scrub hands and don sterile gown and gloves.
c) Ask assistant to open box with sterile pump head and administration set, keeping contents sterile.
d) Hand off the spiked end of the giving set and close the clamp.
For patients below 25 kg open a unit of donor blood.
For patients greater than 25 kg Plasmalyte 148 may be used as the priming solution.
e) Holding the pump head with one sterile gloved finger over the outlet port, put the other end of the administration set into inlet port. Fill with fluid.
f) Shake or tap to displace any bubbles upwards. Check under the magnet for any bubbles.
g) If bubble free you are now ready to change the head.

Discuss with your partners your plan of action for changing the head, assigning roles to each of them.

a) Place a towel on the floor underneath the VAD pump to catch any spills.
b) Betadine swab the tubing of the venous inlet line and between the pump head.
c) Get one non sterile assistant to reduce the flow, clamp the arterial line, turn the pump OFF and then clamp the venous line. Remove the old pump head from the magnetic link.
d) Quickly place two clamps on the venous inlet tubing close to the pump head, and two clamps on the arterial tubing near the pump head, pinching the tubing to avoid splashing.
e) First cut the arterial tubing between the two clamps near the outlet port of the old pump head. Join the new pump head outlet port to the arterial tubing. Shake any bubbles up to the pump head inlet port.
f) Next cut the inlet tubing between the two clamps near the old pump head. With the 50 ml syringe fill the head with the extra volume to remove any air and connect the inlet tubing to the inlet port of the new pump ensuring it is air free.
g) Wipe the pump head clean and recheck that all the air has been removed before reinstituting VAD.
h) Remove the venous clamp first and slowly turn the pump ON watching for any air in the circuit. Increase the pump speed to 700-800 RPM and take off the arterial clamp. Increase the flow to the required rate.

C). Noisy Pump Head.
Thudding Cause: Clot/s in head. Plasma Hb > 0.6 g/L.
Procedure: Change pump head.
Ý in background noise Cause: Pump bearings wearing.
Sounds like iron filings Cause: Pump bearings wearing.

D). Pump Head Noisy & Shaking. Cause: Clot in head.
Procedure: Replace pump head before it splits.

5. Power failure

The Biomedicus console has an internal battery that will run for 3/4 hour at 3000 RPMs. If mains power still OFF after 1/2 hour collect another pump from theatre in readiness for transfer of pump head.

6. Console Power Failure

1. Clamp arterial line.
2. Turn pump off.
3. Clamp venous line.
4. Maintain BP with inotropes, volume or cardiac massage as necessary.
5. Check all electrical connections.
6. Try changing electrical mains lead.
7. Collect another pump from theatre and ensure it will function on battery.
8. Position the replacement console next to the failed one and change the cables for the external drive, flow probe, mains power and the inlet pressure line.
9. Check the zero on the flow probe. Run back onto support and zero the inlet pressure transducer.

7. External Drive Failure

1. Proceed as for changing pump console.
3. Turn pump off.
4. Open top drawer of console and switch motor to internal drive.
5. Move the console to where the pump head can be placed on the internal drive plate.
6. Place pump head on rear drive unit of console.
7. Place patient back onto support

In order to select the appropriate oxygenator, tubing pack, cannulae and priming products the patients blood flow rate must be known. This will be the same as the calculated full flow rate for bypass. The following choice of disposables is used at the Royal Children's Hospital.

Oxygenator	Membrane Size m2	Blood Flow ml/min MinMax	Max Gas Flow Litres per min2	Pum Head Size	Circuit Size
Avecor 0600	0.6	------1000	1.8	BP50	1/4"
Avecor 0800	0.8	------ 1200	2.4	BP50	1/4"
Avecor 1500	1.5	10001800	4.5	BP50	1/4"
Avecor 2500	2.5	18004500	7.5	BP80	3/8"
Avecor 3500	3.5	40005500	10.5	BP80	3/8"
Minimax Plus	0.8	------2300		BP50	1/4"
Maxima Plus PRF	2.3	10007000		BP80	3/8"

There are no recommended maximum gas flow rates for the Minimax and Maxima oxygenators, however the pressure in the gas phase must not exceed the pressure in the blood phase.

Biomedicus Arterial Cannula Flow Range ml/min Size: French Gauge Diameter mm OuterInner 000 -- 500 8 2.661.90 500 -- 700 10 3.332.57 700 -- 1300 12 4.003.24 1300 -- 1800 14 4.663.90 1800 -- 2000 15 5.004.04 2000 -- 2500 17 5.664.70 2500 -- 3500 19 6.335.37 > 3500 21 7.006.04

Argyle Aortic Cannula Flow Range ml/min Size: French Gauge 000 -- 500 10 500 -- 800 12 800 -- 1150 14 1150 -- 1700 16 1700 -- 2500 18 2500 -- 3300 21 > 3300 24

Biomedicus Venous Cannula
Flow Range ml/min	Size: French Gauge	Diameter mm OuterInner
000 -- 350	8	2.661.90
350 -- 500	10	3.332.57
500 -- 800	12	4.003.24
800 -- 1500	14	4.663.90
750 -- 1000	15	5.004.04
1000 -- 1500	17	5.664.70
1500 -- 2000	19	6.335.37
2000 -- 2500	21	7.006.04
2500 -- 3000	23	7.666.54
3000 -- 3600	25	8.337.21
3600 -- 4500	27	9.007.88
4500 -- 5000	29	9.668.54

*NB 15 - 29 FR DLP are percutaneous venous cannulae.

*NB 14 FR double lumen Kendall cannulae are suitable for V-V ECMO up to flows of 400 ml/min.

Double venous cannulation may be required if the flow rates are not adequate to support the patient with a single venous cannula in the presence of very negative pump inlet pressure or if the desired flow rate cannot be maintained due to insufficient venous flow.

Having chosen the appropriate disposables the circuit must be assembled in a sterile manner. The following diagrams show the R.C.H. ECMO priming circuits and the same circuits ready for cannulation.

Diagram 2. Priming circuit for Avecor 0600, 0800, 1500 oxygenators.

Diagram 3. Priming circuit for Avecor 0600, 0800, 1500 oxygenators ready for cannulation.

Diagram 4. Priming circuit for Avecor 2500, 3500, 4500 oxygenators.

Diagram 5. Priming circuit for Avecor 2500, 3500, 4500 oxygenators ready for cannulation.

Diagram 6. Priming circuit for Medtronic Minimax and Maxima oxygenators.

Diagram 7. Priming circuit for Medtronic Minimax and Maxima oxygenators ready for cannulation.

There are three stages of priming the ECMO circuit. The crystalloid prime, protein coating and the blood prime. The following prime constituent quantities relate to priming an Avecor 0800 oxygenator circuit. The assembled circuit including the reservoir must be CO2 flushed through the reservoir prior to priming.

The crystalloid prime is designed to fill the circuit with a balanced electrolyte solution in a bubble free fashion.

1. Clamp the lines to and from the reservoir and close the tap to the blood bag, stop CO2 flushing and disconnect the gas line from the reservoir.
2. Add 500 ml of Plasmalyte 148 and 50ml of 5% glucose to the reservoir.
3. Take the clamp off the reservoir outlet line and allow the circuit to fill. Remove the clamp from the return line to the reservoir; lower the circuit to a level below that of the reservoir to allow the remainder of the circuit to fill.
4. Place the length of tubing between the reservoir and pump head into the roller pump so that the direction of flow is from the reservoir to the pump head. Adjust the roller pump to be occlusive.
5. Start the roller pump. Starting from the reservoir, trace the circuit tapping and shaking components to dislodge any gas bubbles.
6. Next hold the oxygenator so that the blood outlet is uppermost. Shake and hit with the palm of the hand the sides of the oxygenator to dislodge bubbles trapped within it. It may take some time to do this. Make sure that there are no bubbles in the sample/drug line.
7. Hold the heat exchanger with the blood outlet pot uppermost and using the same method ensure that there are no bubbles in it. It is easier to debubble with the water lines disconnected.
8. Once you are convinced that the circuit contains no bubbles you are ready to protein coat the circuit.

1. Turn off the roller pump and remove the tubing from the raceway. Attach the Biomedicus pump head to the external drive unit. Turn the main power switch ON, then turn the pump speed control ON and slowly increase the RPMs to approximately 700 RPM. For each 500ml of Plasmalyte 148 add 100 ml of 20% albumin to the reservoir.
2. Increase the pump speed and allow the fluid to circulate for a few minutes. This allows the albumin to coat the tubing, diminishing the loss (by absorption) of clotting factors and other proteins when the patient is connected to the circuit.

1. While the albumin is circulating the blood used for the prime can be CMV filtered using a leukocyte depleting filter. Ideally the blood will be less than 4 days post collection. If only packed cells are available a unit of fresh frozen plasma of the correct blood type should be thawed.
2. Reduce the pump speed slightly and open the tap to the blood bag. The pump will start to pump the fluid into the bag. When the reservoir is nearly empty stop the pump and clamp the reservoir outlet port. Turn the pump off.
3. Clamp the reservoir inlet port above the Luer connector. Add the blood (and FFP if required) to the reservoir. Unclamp the reservoir outlet port and turn the pump on. The blood will displace the crystalloid fluid in the circuit. When the blood gets to the Luer at the reservoir inlet unclamp the inlet and turn off the tap to the blood bag. Removing most of the crystalloid component maximises the haematocrit of the prime so that patient haemodilution is not as severe on ECMO.
4. For each unit of blood add approximately 15mM Sodium Bicarbonate, 300 units Heparin and 5mM Calcium Chloride to the prime.
5. Ensure the water bath is connected to the heat exchanger and the temperature is set to 37 degrees C.
6. Attach the gas line to the gas inlet port of the oxygenator and start the sweep gas at 700 ml/min 21% oxygen.
7. To calibrate the flow probe ensure that transducer is correctly aligned on the probe and turn the pump off. Clamp both sides of the probe. Adjust the flow zero control behind the top panel of the Biomedicus pump until the display reads zero. Remove the clamps and turn the pump on.
8. Allow the blood to circulate for at least 5 minutes. Remove 2 ml of blood from on of the sample/drug sites in an appropriate syringe. Analyse for blood gases, electrolytes, Hb, ionised calcium and ACT.
Biochemical Adjustment of the Prime.
If the pCO2 is too high allow the blood to circulate for longer.
If the prime is acidotic I.e. -10 Base excess, check first that the pCO2 is not too high and if it is not add 10mM Sodium Bicarbonate and repeat the test after a few minutes.
If the prime is alkalotic i.e. +10 Base excess, check first that the pCO2 is not too low. If it is add 2% CO2 to the sweep gas.
If the Sodium is above 150 mM add 50 ml of 5% glucose and repeat the test.
If the Sodium is below 130 mM add 7mM of NaCl and repeat the test.
If the Potassium is above 6.5mM add 50 ml of 5% glucose and repeat the test.
If the Potassium is below 3 mM add 2mM of Potassium Chloride to the prime and repeat the test.
9. When the prime is within normal biochemical limits turn off the pump and the sweep gas. Clamp the reservoir outlet line above and below the connector. Clamp the reservoir inlet line in 2 places, just above the Y connector on the patient loop proximal to the reservoir and just below the Y connector distal to the reservoir. In a sterile manner detach the pump head inlet line from the connector on the reservoir outlet line. In the same way detach the reservoir inlet line from the proximal Y connector of the patient loop. Replace any lost fluid in these lines with 5% glucose and push the pump inlet line onto the open end of the Y connector without introducing any air into the circuit. Take the clamps off the circuit and turn the pump on. The reservoir is now isolated from the circuit. Although the haematocrit of the prime remaining in the reservoir is low it is an acceptable fluid for volume replacement once the patient is on ECMO and should not be discarded.
10. Disconnect the power and move the circuit to a position next to the patient to allow easy transfer of the sterile loop to the operative field. The sterile wrap is opened and the surgeon takes the sterile tubing. Keep the prime circulating during the move and the cannulation process. The sweep gas should be off until you are ready to commence ECMO.

Diagram 8. Circuit after cannulation.

ECMO Cannulation in Theatre

Turn the pump speed down to about 500 RPMs. Once the surgeon has divided the patient loop (the longer section of tubing between the Y connectors)into venous and arterial ends clamp the patient shunt (the shorter section of tubing between the Y connectors) and the haemofilter shunt also clamp the arterial and venous lines. The aortic cannula is connected to the ECMO arterial line and deaired. A venous cannula in the right atrium is connected to the venous (pump head inlet) line and deaired.

When ECMO is initiated, the clamp from the venous line is removed first. The pump speed in increased slowly to about 700 RPMs. The clamp from the arterial line is then removed and the pump speed increased until the desired flow is attained. With minimum RPMs. This assesses the total obtainable blood flow. Weaning onto support is done very slowly to allow gradual mixing of the prime with the patient blood as there may be a large difference in volumes between the patient and the ECMO circuit.

The gas flow should be started at a rate twice that of the desired blood flow (2:1). A ratio of 3:1 or more is acceptable but the gas inlet pressure must be monitored. A sudden increase can cause the oxygenator membrane to rupture. An ideal pressure for the gas is < 50 mmHg. Most oxygenators have indicated minimum and maximum gas flow rates, which should be adhered to.

A pump inlet pressure monitoring line is connected to the venous cannula connector as soon as possible after initiation of ECMO. A sterile pressure line is handed off from the operative field from a tap on a blood isolator connected to the pressure transducer in the Biomedicus console. This entire line including the isolator must be deaired and flushed with heparinised saline (1 unit/ml) from a 50 ml syringe. Care must be exercised when attaching it to the venous line due to the negative pressure in the venous line. Turn the tap off to the patient to flush and deair the line. Zero the pressure line. Turn the tap to the patient and draw back on the syringe to ensure no air is in the line. Gently flush to the patient and then turn the tap on the isolator to read the pressure. This line must be flushed regularly to prevent it clotting as it monitors cannula position and patient volume status. A continuous infusion of heparinised saline delivered by a syringe may be used.

As soon as the required flow rate is reached and the patient is stable, the ventilator settings may be reduced to minimal maintenance levels.

If the desired flow range cannot be reached check the following;
1. Is the pump inlet (venous) cannula pressure more negative than -60 mmHg? This could be due to hypovolaemia of bad cannula position.
2. Is the patient adequately filled? The patient will require some volume replacement, due to loss from cannulation and compliance of the circuit.
3. Inadequate venous return due to the size or position of the cannula. Check the cannula position. After the chest is closed (not wired together) the position may be checked with chest radiography or echocardiography.

As soon as possible an ACT, blood glucose, Hb and arterial blood gas should be checked.

The ECMO flow must be sufficient to completely support and adequately perfuse the patient. The arterial pressure trace normally has a distinctive pattern, peaking each time the ventricle ejects. On ECMO this trace will begin to flatten as the circuit flow is increased as it does in conventional bypass. When the trace has flattened and there are no peaks 70% - 80% of the cardiac output is being passed through the circuit.

The ECG should remain normal. The coronary arteries are directly perfused with fully saturated blood from the ECMO circuit ensuring a normal oxygen supply to the myocardium.

Inotropic drugs can be weaned quickly and then stopped when adequate flows have been established. Our centre prefers to maintain a dopamine infusion at 2.5 - 5 ug/kg/min to optimise splanchnic flow and renal perfusion.

The goal is to maintain adequate flow. Adequate flow is best defined as the amount of flow that allows for a normal pH, mixed venous pO2 and all other organs to function normally. Flow through the poorly functioning lungs acts as a right to left shunt. Increasing pump flow will allow less blood through the lungs, sending more to the oxygenator. Once the patient has been stabilised the pump flow may be decreased to keep the paO2 in the 85 - 100 mmHg range.

The patient must have an adequate circulating blood volume to obtain good flow rates. Blood sampling may average 50 ml per day in the neonate on ECMO. Blood may also be lost from the cannulation sites. Therefore a careful and complete fluid balance, monitored hourly, is essential. Decisions on volume replacement are made depending on the Hb, blood protein levels or plasma levels. Packed red cells are given if the Hb drops below 9 gm/dl. FFP or albumin if the Hb is above 9 gm/dl and platelets if the platelet count is less than 50,000.

Sodium citrate preservative in donor blood binds with ionised calcium; therefore calcium gluconate or calcium chloride is usually administered with each 100 ml of blood or FFP. Total serum and ionised calcium levels should be monitored 8 hourly.

The size of the arterial cannula contributes to the resistance in the circuit as it does in CBP. Haemolysis can occur with high flow through narrow orifices so the larger the cannula the less haemolysis will occur. This is more critical than with conventional CPB because of the time period on support.

Once the patient is stable the haemofilter shunt can be opened to allow flow of 20 - 40 ml/min through it. The same can be done for the patient shunt.

1. Over hydration resistant to high doses of diuretics.
2. Parenteral nutrition restricted due to fluid limitations
3. Prevention of hyperkalemia or azotemia
4. Impaired pulmonary diffusion with circulatory failure.
5. Hypernatremia resistant to natriuretic drugs.

The haemofilter is inserted into the shunt line used for sampling and drug infusion. If not primed at the same time as the circuit a tubing insert can be placed in the position of the haemofilter. This can be replaced by the haemofilter at any time.

The need for dialysis or ultrafiltration has been identified as risk factors for death is some papers. In our unit both dialysis and ultrafiltration are used routinely (as required) during both VAD and ECMO and have not emerged as independent risk factors.

1. Air in Circuit.

a) Air in venous line or pump head only.

1. Air infused into right atrium through I.V. lines.
2. Venous cannula position.
3. Connector from cannula to circuit.
4. Tap open on venous pressure line.

Management

1. Clamp off the ECMO cannulae and shunts.
2. Turn the pump off.
3. Ventilate the patient and maintain cardiac output. Find and fix the site if the leak.
4. Attach a 50 ml Luer lock syringe to the tap on the Luer connector on the venous line.
5. Take the pump head out of the external drive unit.
6. Hold the pump head lower than the venous cannula, shake and tap the circuit to move the air up towards the syringe.
7. Aspirate with the syringe until all the air is removed.
8. Put the pump head back in the external drive unit.
9. Re-institute ECMO. Remove the venous clamp, increase pump speed to 700 RPMs, remove the arterial clamp and increase pump speed to required flows.
10. Re-establish the correct flows through the shunts.

b) Air in oxygenator.

1. Improper priming procedure.
2. Membrane rupture.
3. High gas flow with low pump flow.
4. PO2 in blood too high for P. atmosphere.
5. From pump head or venous line.
6. From connectors on the oxygenator.
7. From sample/drug infusion sites.

Management

1. Clamp ECMO lines between the pump head and the oxygenator and any shunts.
2. Turn the pump off.
3. Ventilate the patient and maintain cardiac output. Find and fix the site of the leak.
4. Connect a 50 ml Luer lock syringe to a tap in the haemofilter shunt line and tilt the oxygenator so that the shunt line is higher than the air in the circuit.
5. Tap and shake the oxygenator to move the air upwards and aspirate the air into the 50 ml syringe until all the air is removed.
6. Re-institute ECMO.

If you suspect that the oxygenator membrane has ruptured the patient must be supported by conventional methods until a new oxygenator is primed and used to replace the ruptured one.

c) Air in haemofilter line or circuit.

1. Improper priming of haemofilter.
2. Loose connector in haemofilter circuit.
3. From infusions into the haemofilter.

1. Clamp the haemofilter lines between the oxygenator and the haemofilter, and the line between the sample/drug site and the oxygenator.
2. Turn off any infusions and attach a 50 ml Luer lock syringe to one of the sample/drug sites. Tap the air up from the haemofilter and aspirate it into the syringe.
3. Once the air has been removed re-institute haemofiltration and the infusions.

d) Air in the top of the heat exchanger.

1. From the oxygenator due to a ruptured membrane.
2. From infusion lines of the haemofilter or sample/drug sites.
3. Loose or leaking connectors between the oxygenator and heat exchanger.
4. A leak in the body of the heat exchanger.

Management.

1. Check that air is not passing into the arterial line. If it is, COME OFF ECMO. (Small amounts of air should remain trapped at the top of the heat exchanger.)
2. Clamp shunts and the arterial and venous lines. Turn the pump off.
3. Ventilate the patient and maintain cardiac output. Find and fix the site of the leak.
4. Attach a 50 ml Luer lock syringe to a tap on the sample/drug site manifold and open the tap. Lift the haemofilter and remove the oxygenator from its holder. Tap the air from the heat exchanger into the top of the oxygenator and up into the shunt line towards the syringe.
5. Aspirate the air with the syringe and when all the air has been removed close the tap and place the oxygenator back in the holder.
6. Re-institute ECMO and remove the clamps from the shunts.

e) Air in the arterial line and patient.

1. Oxygenator rupture (? Gas port obstructed).
2. Loose connector at cannula.
3. Heat exchanger leak.
4. Venous line tap left open and circuit filled with air via shunt line if on low flow.

Management.

1. Clamp arterial, venous and shunt lines. Turn pump off.
2. Put patient head down (Trendelenburg position) so that air will move from the lower half of the body.
3. Ventilate the patient and maintain cardiac output. Find and fix the leak.
4. Have plenty of volume available to give and a person to give it.
5. Attach a 50 ml Luer lock syringe to the three way tap on the connector on the arterial cannula and open the tap.
6. If air is seen in the cannula aspirate blood from the arterial cannula to remove the air seen in it. Clamp the cannula once the air has been removed.
7. Remove the clamp from the arterial line and tap the line to move the air to the syringe and aspirate it. Give volume as required.
8. Check the rest of the circuit for air. Tap the oxygenator, if any air appears at the top of the membrane do not re-institute ECMO as the membrane has been ruptured and the oxygenator needs to be replaced.
9. If no more air is seen re-institute ECMO.

2. Oxygenator Failure.

a) Air in the top of the oxygenator.

Cause: 1. Membrane rupture.
Management: Change the oxygenator.

b) Clots in the oxygenator.

Cause: 1. Inadequate anticoagulation.
Management: Increase ACTs.
2. Less than rated blood flow for the oxygenator.
Management: Increase flow to patient or through shunts.

c) Decreasing patient saturation.

d) Decreasing post oxygenator pO2.

Repeat pre and post oxygenator gases, increase FiO2 if possible.

e) Increasing pCO2 .

Increase sweep gas if not at maximum.

f) Blood leaking from gas exhaust port.

Ruptured or holed membrane. Change oxygenator.

g) Plasma leak from Minimax oxygenator.

Monitor pre & post oxygenator gases. Change before pO2 decreases and pCO2 increases to intolerable levels.

3. Pump Head Failure.

If the pump head start to leak, if the volume loss is very small the pump head can be changed as soon as is convenient as long as the volume is replaced. If the leak is large the head must be changed immediately. For this the patient must be taken off ECMO. The method is the same as described in the VAD section.

The low flow alarm should sound, the venous pressure will become more negative and as the flow decreases so will the saturation. If the situation is prolonged, ventilate and support the patient. Decreased blood return to the pump may be caused by:
1. Change in patient head position.
2. Change in venous cannula position.
3. Patient hypovolaemia due to increased diuresis or bleeding.
4. Fibrin clot in pump inlet line.

The low flow alarm should sound and the arterial cannula pressure will increase, but the venous pressure will remain the same or become more positive. The patient's saturation may fall as the flow decreases. Increased resistance to flow can be caused by:
1. Increased arterial pressure.
2. Change in patient head position.
3. Change in arterial cannula position.
4. Clots in:

- oxygenator.
- heat exchanger
- arterial cannula
- arterial tubing.

Increasing arterial pO2 :

Patient looks generally well:
Improved pulmonary function.
High ECMO flow rate.

Patient looks unwell:
Tension pneumothorax?
Hemothorax?
Pneumopericardium?

Tissue necrosis (ongoing acidosis):
Infection?
Poor perfusion.

Decreasing patient pO2 :

Cyanosis, acidosis.
Pneumothorax or atelectasis
Ventilation malfunction, patient secretions
Fluid in vent. Tubing
ECMO flow to patient too low.
Circuit shunt flow too high.

Decreased pulmonary blood flow:
?Patent ductus arteriosus.
Increased pulmonary hypertension.

Mechanical:
Gas tubing leaks or not connected.
Oxygenator failure.
Sweep gas FiO2 too low.

CNS Injury:
Seizures impairing pulmonary inflation.
Massive intracranial haemorrhage

Patient looks generally well:
Improving pulmonary perfusion.
Improved oxygen extraction.

7. Changes to patient pCO2.

Increasing pCO2:

Patient tachypneic, acidotic:
Gas flow rates too low.
Needs more ventilation support.
Pneumothorax.
Citrate or Bicarbonate overload from transfusions.

Mechanical:
Oxygenator failure.
Endotracheal tube problems.

Decreasing pCO2:

Patient apnoeic, alkalotic:
Gas flow rates too high.
Over ventilated.
Lung compliance improving.

Patient tachypneic, alkalotic:
High pCO2 in post oxygenator gas.
Cerebral dysfunction.

Patient tachypneic, acidotic:
Other organic acid in blood.

8. Changes in urine output.

Decreased urine output:

Hypovolaemia:
Patient hypotensive and mottled.
Give volume.

Pre-ECMO hypoxia:
Ischaemic kidney damage.
Increase pump flow. Increase diuretics
Try haemofiltration.

Capillary leak syndrome:
Oedematous patient. Poor perfusion.
Increase pump flow, start diuretics.
Start or increase inotropes.

Low pump flow:
Increase pump flow.

Patent Ductus Arteriosus?
Do cardiac echo to confirm.

Haemoglobinuria:

Red serum noted.
Check plasma Hb.
Plasma Hb > 1.0 g/L. Pump failure, clots in circuit or pump. Change pump head or circuit.
Renal Dysfunction.
Do renal ultrasound.
Pump speed too high.
Reduce pump speed.
Pump inlet pressure < -60 mmHg. Check cannula & patient position, give volume if required.
Patient has sepsis/DIC. Low platelet count, prolonged PT & APTT. Elevated FDPs. Culture blood, check PT, APTT & FDPs.

Increased urine output:

Response to improved blood flow.
Post-injury diuresis.
Improving pulmonary status.
"Recovery diuresis" post capillary leak.

9. Patient Bleeding.

Blood pressure decreased, pulse rate increased.

ACT too high?
Reduce heparin infusion rate.

Decreased Hb, visible bleeding.

Due to pre-ECMO procedure.
Investigate wound site.
Heparin dose and ACT too high.
Reduce heparin infusion & check ACT.

Internal bleeding.

Pneumothorax etc.
Check with X-ray.
NEC, Fontanelle tense: seizures, CNS Changes.
Trauma.
Check with ultrasound.

Platelet count low.

Destruction of platelets by circuit.
Transfuse platelets.
DIC.
Check PT, APTT, FDPs, transfuse
Platelets, FFP etc.

Infection/Sepsis.
Culture and treat with appropriate antibiotic.

The ELSO results for ECMO tabulated for July 1997 show that of 16,098 patients supported to date by reporting centers, 2,051 were in the 'cardiac' category. Within this group, 1563 had cardiac surgery prior to support, 114 had a transplant related indication, 57 had myocarditis, 95 had other cardiomyopathies, and 222 did not fall into any or these categories. Overall survival for the 2051 children supported was .42. If one looks at the results of ECMO in children stratified by indications, one finds that to date they have been significantly better for pulmonary support than for cardiac support (survival probability .75 vs .42, p = .0001).

Results with short term VAD and ECMO in our own unit and most others reflect a policy of expanding the indications to include nearly all cardiac surgical patients who are not expected to survive without support. Whether this strategy is appropriate or not is a decision to be taken by each team in the context of local resources and philosophy. To most teams a 30% to 40% long term survival probability would immediately justify the effort and expense, especially if the child might have minimal or no disability. Thus improvements in the technical aspects, safety and efficacy of the centrifugal pump VAD may be obscured to a degree by the liberalisation of its indications for use.

The future of centrifugal VAD might be considered uncertain in light of recent advancements with paracorporeal or totally implantable pulsatile systems. The importance of pulsatile flow has been debated for many years, but the real issue is suitability for safe long term support. Examples of systems which may be suitable for children, or in some cases infants include the following: Berlin Heart, MEDOS/HIA assist (both in clinical use in Europe), the Toyoba and Zeon pumps (in clinical use in Japan), the Thoratec VAD (in clinical use worldwide including some application in patients < 20 kg.), the University of Pittsburgh mini-centrifugal pump (not yet in clinical use), the Pierce-Donachy paediatric system (not yet in clinical use), the Jarvik 2000 and others. These devices will play an important role in the establishment of long term support for recovery for bridging to transplantation. Also there are a number of devices available for children above 50-60kg (flow > 2.5 - 3 lpm), who from a technical point of view could be considered similarly to adults. For short term support however the role of these devices remains controversial. The costs involved for the clinically available systems are very much greater than centrifugal pump VAD or ECMO, both for the driving system and the disposable components required per ventricle per patient. We believe that for most cardiac units, especially those not involved in transplantation, that the simplicity, availability, cost effectiveness and good outcome (in selected cases) will ensure the place of the centrifugal pump VAD and ECMO in our surgical armamentarium for the foreseeable future.

Muehrcke DD, McCarthy PM, Stewart RW, et al. Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock. Ann Thorac Surg 1996; 61: 684-91.