Current Approaches to Minimizing Inflammation
(Reviewing pharmacological and non pharmacological strategies used to reduce
inflammation during CPB on Infants & Children) CPB in general and especially in infants and children undergoing cardiac surgery may lead to a systemic inflammatory response. Efforts to reduce CPB-related inflammation include pharmacological and perfusion strategies. Since the late 80s, intra-operative ultrafiltration has been used to alleviate CPB’s toxic effects. It diverts blood flow to the CPB circuit & hemo-concentrator, removing fluid and small molecules, including activated complement factors & cytokines up to 66kDa in size.
Cardiopulmonary bypass is associated with inflammatory reaction & subsequent edema, particularly in small infants and neonates. Cardiopulmonary bypass causes activation of inflammatory cascades, such as complement, kinin–kallikrein, and the coagulation system, as well as stimulation of neutrophils and platelets. These systemic inflammatory responses also elevate the levels of the substances that are capable of increasing vascular permeability, such as bradykinin, C3a, C5a, tumor necrosis factor-, interleukin-1 (IL-1), IL-8 and so on resulting in edema formation and organ dysfunction.
In1990s, Ridley and coworkers tried to reduce the detrimental metabolite load and to adjust the unphysiological concentration of the electrolytes by hemofiltration for the primed blood. They demonstrated that this technique maintained the level of electrolytes within physiologic range and minimized the changes in blood glucose and lactate in pediatric patients during and early after CPB.
In our study, we found that only hemofiltration is not enough to reduce CPB-related inflammation.
1. When blood travels through the CPB, it is traveling through something much different than its usual familiar environment.
2. Blood is now flowing through polyvinyl chloride tubing, although the tubing is compatible with blood, blood was not obviously not made to travel through the tubing.
3. Because the blood is being introduced to this foreign material, it is only natural that the body tries to protect itself.
4. Therefore Systemic Inflammatory Response Syndrome (SIRS) often occurs during and continues its effects after CPB.
Since the first successful use of heart-lung machine, there has been many advances in CPB. Each new change or addition to the machine has been an attempt to reduce the risks that are described above and to ultimately save lives. But in reality more than 70 years after the first successful use of the heart lung machine and the extension of million of lives, blood and the heart-lung machine remain incompatible. Ways to increase compatibility and reduce the risks such as inflammation, micro emboli, and heart lung complications will be discussed here. Hence we decided to use coated circuits since year 2018, which mimic the vascular system instead of normal PVC customized tubing sets. The moment blood flows through unfamiliar surfaces, the body starts producing inflammatory mediators. Together we employed Subzero-balance Ultrafiltration (SZUF), a continuous ultrafiltration method throughout the entire duration of CPB exposure. Reducing the heparinization for a target ACT of 300 to 350 seconds instead of 480 seconds is one of the greatest advantages of using PC coated circuit.
Introduction for Coated Tubing:
The development of a surface that mimics certain properties of living cells including the resistance to protein adsorption, presents a way to prevent the thrombotic embolization of the body vessels.
The surfaces in contact with blood are masked by phosphorylcholine (PC) which has been identified to be an
essential part of the cell membrane of the Red Blood Cells. This Bio-mimetic substance is used to coat the surface in contact with blood, the advantages being to potentially suppress from the inflammatory response mechanisms.
Features of Coated Tubing
1. Resistant to protein deposition
2. Non-thrombogenic
3. Resistant to bacterial adhesion
4. Non-inflammatory
5. Durable
6. Non-toxic and bioinert
7. Hydrophilic and dehydration resistant
Benefits of Coated Tubing
1. Increases bio-compatibility of device
2. No adverse reactions
3. Reduces clot formation
4. Reduces biofilm/infection
5. Increases patient comfort
6. Reduces device rejection and fibrosis
7. Prolongs device effectiveness in-patient
8. Enables rapid regulatory approval
9. Lubricious-increases ease of handling
We experienced that by using coated circuits & employing Sub zero ultrafiltration (SZUF) have reduced the inflammatory mediators. The reduction of initial inflammatory response in the early period of CPB by using coated circuits may attenuate subsequent inflammatory reactions, rather than only depending on hemofiltration (PUF, CUF, ZBUF, MUF). Our results are very much encouraging as most of the patients are extubated On-table.
CONCLUSION
Cardiac surgery has certainly advanced over the years, particularly with the development of the Cardio-Pulmonary Bypass machine. Being able to operate on a completely motionless heart is an incredible progression that may help
save lives. The CPB system itself has come a long way in development since the first surgery and will continue to develop to enhance every patients quality of life.
Although the CPB is an amazing procedure, many adverse effects can occur compromising the surgical output.
Preventing these adverse effects is an ongoing process demanding our serious attention.
Using coated membrane oxygenators and adding heamofilters throughout the circuit have been useful in preventing micro emboli from traveling throughout the body. Research has shown that coated circuits may reduce inflammation, bleeding, the need for blood transfusions, and pulmonary injury. Target ACT is reduced to 300-350 seconds requiring a lower dose of heparin.
Ultrafiltration is being studied and found to reduce inflammation and pulmonary harm. Medications such as
corticosteroids are also identified to help reduce complications and the inflammatory response.
All healthcare professionals hope that the incidence of harmful consequences of Cardio Pulmonary Bypass will continue to decline and someday the risks associated will close to be near zero and the Perfusionists will ensure absolute safety and can able to perfuse without changing characteristics and properties of blood. Until that day, research will continue and new methods will be tested to improve the already incredible procedure.
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