Techniques For Extracorporeal Circulation Biology Essay

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Extra Corporeal Membrane Oxygenation originated from the first blood oxygenator, which was developed in the 1950s by Dr.Gibbon Jr.In 1930 he started working on the techniques for extracorporeal circulation, when a patient died from pulmonary hemorrhage. Thus, his first interest was pulmonary support and not cardiac support. The development of membrane oxygenator was also significant. The first oxygenator sustained blood-air interventions. It was observed there were various complications and organ deteriorations after limited a time. Experiments conducted showed the negative effects of blood air interface. Hence, the next goal was to develop the membrane oxygenator.Clowes built the first membrane oxygenator using polyethylene and in 1956 this device was successfully applied in cardiac surgery. Then, came a need for improving the membrane oxygenator.Kammermever discovered that dimethyl-polysiloxane membranes allowed much better diffusion rates rather than polyethylene. This became the membrane of choice and the improved diffusion rates of this membrane made extended life support possible. Bleeding was still a problem, and the numerous transfusions that would be needed for extended support made the therapy unfeasible.Therfore; improved anti-coagulation management was looked upon. Robert Bartlett team in the mid-1960's showed that longer support times was possible by reducing the heparin dosage. In 1972 a patient was successfully supported by use

of membrane oxygenation for 3 days. Further developments in membranes gradually were observed. In 1960's extensive research were done on materials and techniques.Dr Theodore Kolobow perfected the design of flow patterns of membrane lung and the

method of layering the silicone.Dr Kolobow also designed vascular access catheters and demonstrated that ECMO could be studied in awake animals. The 70's urged for a device that could provide extended heart-lung bypass. Extracorporeal oxygenation was well suited to allow healing time in respiratory failure. In 1975, both the National Institute of Health and the lung Division of the Heart and Lung Institute began a study on ECMO.In the same year the first newborn infant was successfully sustained using ECMO under the care of Dr.Bartletts. Hence he was better termed as father of ECMO.He developed the concept of titrating heparin - which substantially reduced bleeding complications. He also refined the circuit design with exclusion of stagnant flow areas. Further studies were conducted on adult and pediatric patients. The hurdles observed on adult patients were numerous. The study included centers with no ECMO experience. Patient populations were dominated by the influenza epidemic. There were severe bleeding problems observed.300 patients was to perform for the study but at 92 the study was stopped due to poor results.ECMO success rate was 10%.Adult ECMO was not further investigated or performed in the US. By 1981 Dr.Bartletts team treated 45 newborns with a success rate over 50%.this lead to establishment of more ECMO centers. By 1986, 715 neonatal cases were reported at 18 centers; with favorable success rates of about 80%.there was a vast improvement from 50% in 1986.

Fig 1: timeline of Ecmo development

Physiology of ECMO

Robert Bartley quoted that extracorporeal life support is achieved by draining venous blood, removing carbon dioxide (CO2) and adding oxygen through an artificial lung and returning the blood to the circulation via a vein (venovenous) or artery (venoarterial). The physiologic goal is to improve tissue oxygen delivery, remove CO2 and allow

normal aerobic metabolism while the lung rests or is provide with cardiac assist.

Gas exchange may be divided into two types:

Pulmonary respiration refers to the gas exchange between blood and inspired gas

Tissue respiration refers to the exchange of oxygen and carbon dioxide at cellular level.

CO2 excretion is much more efficient than oxygenation in the lung, CO2 removal can be maintained at normal levels even during severe lung dysfunction.

Two Types/modes of ECMO:

Arterial Veno Bypass

Veno Venous Bypass

AV bypass include changes in O2 consumption, Arterial/venous saturation, Onset, O2 consumption decrease (chatecholomines is reduced, less metabolic stress).Arterial saturation 95% and flow adjusted to maintain arterial/venous saturation. Bleeding - decrease in venous return, decrease in venous saturation - transfusion. Without lung function and ejection of heart arterial saturation decrease.

VV bypass include Arterial/venous saturations - nearly the same 85%.Decreased ventilator settings, chatecholomines, resulting in return to normal oxygen consumption.

Increased muscular activity with seizures - increased VO2, decrease art/ven saturation.

Bleeding - decreased venous return - decreased ven/art saturation - transfusions

Components of ECMO

The circuit use for ECMO has its realization in the heart lung bypass machine used for cardiothoracic surgery, but have been modified for use in long term support. The main components of an ECMO circuit are

venous reservoir and roller pump


heat exchanger

arterial filter

1. Venous Reservoir

Roller pump systems require a continuous availability of blood at the inlet to avoid development of large negative pressures and hemolysis. The most common approach is to provide gravity drainage from the drainage cannula into a small assist reservoir, or bladder, situated just before the pump inlet. Gravity assist is achieved by placing the reservoir and pump approximately 100cm below the level of the cannula, providing a hydrostatic siphon for drainage and maintaining a positive pressure at the pump inlet. The reservoir also buffers against fluctuations in drainage. If drainage decreases, for example, because of hypovolemia, the reservoir will begin to empty, signaling the need for correcting the reason for poor drainage. Most roller pump systems have the capability of servo regulation. A switch situated in the reservoir holder opens when the bladder empties, turning off the pump and allowing time for filling of the reservoir. With the pump off, the bladder refills and the pump resumes operation.

Blood Pump

Two principal pump technologies are currently used for ECMO and are the same used for cardiopulmonary bypass. The most popular is the occlusive roller pump, a rotary

Positive-displacement pump in which a roller head squeezes a length of blood tubing against a backing plate as the roller rotates (Fig. 2). This pump is used with gravity

drainage, so an assist reservoir is required at the pump inlet to maintain a continuous preload, as inlet occlusion can result in large negative pressures (500mmHg or more). Servo regulation with an assist reservoir is used to prevent this complication. The pump is also insensitive to outlet occlusion and can generate pressures high enough to cause tubing rupture, requiring continuous monitoring of circuit pressures. The degree of occlusion of the tubing when compressed by the roller head must be carefully calibrated to avoid hemolysis (from over-occlusion) and loss of pumping effectiveness and flow accuracy (from under- occlusion). When properly used and monitored, this type of pump has a low incidence of complications. The centrifugal pump is a nonocclusive pump that generates flow via a spinning rotor with vanes (Fig. 3). The device generates an active suction at the pump inlet, eliminating the need for gravity drainage and an assist reservoir, although these can be used. Occlusion of the inlet or outlet will result in only modest negative inlet or positive outlet pressures (Fig. 4) (24) and, thus, is safer from mechanical complications, but can lead to rapid hemolysis in these circumstances. Hemolysis is the most common complication of the use of a centrifugal pump, but can be minimized by maintaining a low-pressure-flow ratio across the pump. Achieving this ratio requires adequate venous drainage, a low-resistance oxygenator, and a sufficiently large return cannula to prevent high-circuit pressures. A third pump type, the nonocclusive roller pump, (also known as the M pump in the United States and the Rhone-Poulenc pump in Europe) has had limited use in ECMO but possesses the desirable characteristics of the other two pump types. It is a peristaltic pump consisting of a distensible silicone chamber stretched around a rotor. Unlike an occlusive roller pump, there is no compression against a backing plate. The pump passively fills through

distension of the chamber and the rotor compresses the chamber against its natural recoil force. If the pump fails to fill, the chamber collapses and only a minimal negative

pressure is generated. If the outflow is occluded, the chamber does not collapse under the rotor and blood flow ceases with only a modest build-up of pressure. Each of these pump types (roller and centrifugal) has advantages and disadvantages for use in extracorporeal support that are summarized in Table 2

2. Oxygenator

The artificial lung, commonly called an oxygenator even though it transports carbon dioxide in addition to oxygen, must provide the necessary oxygen and carbon dioxide

transfer to support or even fully replace the natural lungs. The need to provide support for days to weeks places additional requirements on oxygenator design. Two designs

have been traditionally used for ECMO, and new designs are emerging. A comparison of the characteristics of these devices along with an ideal device is given in Table 3.

4.5.1. Silicone Membrane Devices. The spiral-wound solid silicone sheet membrane lung (Fig. 6) was developed by Kolobow and Bowman (25) and has been used in the majority of ECMO cases since its inception. It consists of two long sheets of silicone sealed at the edges and wound on a polycarbonate support. Gas manifolds are attached at the ends, and a manifold provides blood distribution between the rolls. Six sizes are commercially available at present (0.6, 0.8, 1.5, 2.5, 3.5, and 4.5 M2). The three larger devices have an integrated heat exchanger.

4.5.2. Micro porous Hollow Fiber Devices. Micro porous hollow fiber devices, which are most commonly used for cardiopulmonary bypass, are increasing in popularity for

ECMO because of their improved performance despite some of the problems with long-term support. Hollow fiber membranes are constructed of hydrophobic polymers with pores that range in size from 0.2 to 0.7 microns. These pores remain occupied with gas and present a gas-liquid interface for gas exchange. When in contact with water, or in short-term contact with plasma, the stability of these interfaces is maintained. After 12 or more hours of contact with plasma, however, leakage of plasma ensues and gas exchange is impaired, the cause of which is most likely the adherence of bipolar phospholipids creating a hydrophilic surface (26). Polymers used for construction of noncomposite commercial hollow-fiber membranes include polypropylene, polymethylpentene, and poly-4-methyl-1-pentene (27). The fibers have an inner diameter ranging from 165 to 240 mm and a wall thickness between 30 and 90 mm.

Skinned asymmetric hollow fibers manufactured from polymethylpentene and poly-4-methyl-1-pentene have a thin layer of nonporous polymer at the blood contacting surface. Composite membranes consisting of a thin coating of siloxane (28-30) or 1,3,5,7-tetramethylcyclotetrasiloxane over a polypropylene hollow-fiber base eliminate

the air-fluid interface and improve biocompatibility, yet are thin enough (0.2 mm) such that gas exchange is not compromised (Fig. 7) (27). Silicone, used in the coiled sheet membrane lung, has also been fabricated into hollow fibers (31-35). Structural stability is maintained with a reverse-phase blood flow (external to the fibers).

4.5.3. Bubble Oxygenator. The third type of artificial lung, the bubble oxygenator, was the original artificial lung developed for cardiopulmonary bypass, but is not used in prolonged ECMO support. It is a low-resistance device, but it is associated with activation of blood components because of direct contact of air with blood.

4.5.4. Gas Transfer. Permeability for oxygen and carbon dioxide differ considerably in artificial lungs, with carbon dioxide having a 5-fold or greater permeability than oxygen, which is approximately offset by the difference in diffusion gradients, with oxygen having a much higher diffusion gradient (PB PH2O P VO2, approximately 650mmHg) than carbon dioxide (P VCO2 PoutCO2, approximately 40mmHg). PB is barometric pressure, PH2O is the water vapor pressure in the artificial lung gas phase, P V O2 the mixed venous oxygen partial pressure, P V CO2 the mixed venous partial pressure of carbon dioxide, and PoutCO2 the partial pressure of carbon dioxide at the outlet of the artificial lung. However, the effective diffusion rate is a function of diffusion not only through the membrane material itself, but also through the blood boundary layer, which has a much lower diffusion rate (see Determinants of artificial lung gas transfer below).

A nonlinear relationship exists between blood flow through an artificial lung and the oxygen delivery achieved by the device (Fig. 8). The rated blood flow of a membrane lung is the blood flow through the device at which blood entering at 70% saturation achieves 95% saturation at the outlet, simulating the conditions of the natural lungs between mixed venous saturation and arterial saturation. Higher flows, while still allowing a higher overall gas transfer, extend into the nonlinear relationship between blood flow and oxygen transfer (Fig. 8). The linear portion of the curve represents flow limitation, whereas the nonlinear portion at higher flows represents diffusion limitation of gas transfer.

3. Heat exchanger

The Heat Exchanger is used in cardiopulmonary support procedures to cool and warm the blood. Typical applications include: total body perfusion, coronary perfusion, rapid infusion, and cardioplegia. The recognized standard for ECMO procedures include

Stainless steel heat exchanger tubes providing reliable and consistent performance

Double seal between blood and water compartments for added safety, Luer-lock port on blood inlet to facilitate air removal, Blood outlet temperature adapter for accurate blood temperatures, Silicone coating applied to stainless steel tubes and inserts to enhance blood biocompatibility, Blood flow rate up to 2 L/min.

1.During rapid warming required for cardiac surgery, it is important to place the heat exchanger proximal to the oxygenator

2.Theoretical problem of generating bubbles by heating saturated blood has proved to be less relevant for the more gradual heat gradients seen during ECMO

3.In long term extracorporeal circulation, normothermia is maintained

4. Best position to place heat exchanger is after the membrane lung

a) Allows blood to be at normothermia just prior to entering body after blood has cooled in oxygenator

i) Membrane lung ventilating gases cool when expanded from high pressures

ii)Significant evaporative heat loss as the dry ventilating gases become saturated with water vapour

iii) Higher gas flows exacerbate cooling effect

b) Especially relevant to infants & neonates; heat exchanger position is less important in older children and adults

5. Countercurrent water flow from the heater must warm the blood to body temperature without excessive localised heating that may cause haemolysis

6. After leaving the oxygenator, blood flows through a separate heat exchanger where it is warmed to 37°C

7. Placing the heat exchanger immediately after the oxygenator will warm the blood before it returns to the patient

8. In adults not so important as may be using an integrated oxygenator-heat exchanger

4. Arterial filter-ALF

ALF is a Class II device and the typical system consists of an outer housing having a top and bottom section, an inner housing, and a filter element. The filter element is disposed within the outer housing, and the inner housing is disposed between the filter element and the housing. The inner housing is separate from the outer housing and extends the entire axial length of the filter element. Fluid enters the device through an inlet. The majority of the fluid then rises in a centripetal motion where any large air bubbles exit through a vent at the top section of the outer housing. The fluid then flows through openings in the top and bottom of the inner housing. After entering the inner housing, the fluid passes through a filter element, where filtration takes place, and exits through the bottom section of the housing through an outlet. There are basically two types of filters. One is screen and other is depth filter. Most filters in the arterial line are screen filters. A bypass line around the arterial line filter is recommended. Pressure drop across filter should be monitored to detect filter obstruction. Bypass line around filter is usually occluded by a clamp. The ALF is always positioned after oxygenator and distal in the circuit.

The manufacturing process involved in production of ALF is vast. Encapsulating and sealing of ALF is done using polyurethane potting or ultrasonic welding. Major criteria's concerned are

(a) providing a cone having a tip end and an open end and made of a filter material

(b) providing a support element having a plurality of concentric annular members mounted on a base and having outermost and innermost concentric annular members

(c) aligning the central axes of the cone and the support element with the tip end of the cone closest to the support element

(d) inserting a portion of the cone into a circular area between two concentric annular members by placing a forming sleeve inside the cone and inserting the forming sleeve between the two concentric annular members, the concentric annular members being generally cylindrical and having an interior and an exterior.

The ALF after manufacturing has to successfully pass the stringent non clinical tests and in-vitro tests to enter into the market. various FDA and ISO regulations are levied on the product.


The patients on ECMO are critically ill. Once the patient is placed on ECMO, the work of getting the patient off ECMO begins. Anticoagulation, prophylactic antibiotic, mild sedation with neuromuscular blocking agent, cardiopulmonary bypass and nutritional support is carefully monitored. Parents often need some emotional and psychological support. The number of ECMO cases continues to decline. This may be because of increased used of nitric oxide, HFOV, HFJV. It is interesting to note that survival on ECMO has also decreased. This may be due to delay in ECMO therapy because of pre ECMO trial of alternative treatment. The success of the therapy depends on prompt diagnosis and early initiation of treatment.