Effects of Cardiopulmonary Bypass

Ns. Ida Simanjuntak, S.KepPerfusionist Staff

National Cardiovascular Center Harapan KitaJakarta

Effects of Cardiopulmonary Bypass Glucose metabolism

Hyperglycemia usually accompanies the stress response associated with CPB.

A more common complication of paediatric CPB is hypoglycemia. This is largely because of the decreased glycogen stores and reduced hepatic potential for gluconeogenesis.

In patients with CHD, hepatic perfusion may be impaired further, which leads to compromised liver function. Neurologic consequences of hypoglycemia are aggravated by hypothermia and other factors that may modify cerebral perfusion. Glucose monitoring during CPB and rapid correction with dextrose is essential for decreasing morbidity resulting from paediatric heart surgery.

Effects of Cardiopulmonary BypassHaematologic effects

Paediatric patients develop a more exaggerated response to CPB. The inflammatory response is inversely proportional to the patient’s age. Interleukin (IL)–8 and IL-6 production have been linked to this inflammatory reaction, with their expression linked to the duration of CPB.

The synthetic surfaces of the bypass circuit have been associated with activation of inflammatory mediators. These include activation of the complement system, including plasma-activated complement 3 (C3a). A potent stimulator of platelet aggregation, C3a causes histamine release from mast cells and basophils, increases vascular permeability, and stimulates WBCs to release oxygen free radicals and lysosomal enzymes. Elevated levels of C3a have been linked to the duration of CPB.

Effects of Cardiopulmonary Bypass

Haematologic effects Contact of blood with the bypass machine surface

activates platelets and causes an increase in thrombus formation. If not corrected, activation of coagulation and fibrinolytic pathways can lead to excessive bleeding. Expression of binding proteins on endothelial surfaces leads to extravascular migration of neutrophils and subsequent tissue injury.

Activated neutrophils obstruct the capillaries, thus limiting reperfusion of ischemic tissue (i.e. no-reflow phenomenon).

Effects of Cardiopulmonary BypassStress response

Low perfusion, hypothermia, and exposure of the blood to the tubing and surface of the pump cause release of hormones and other substances, including catecholamines, cortisol, growth hormone, prostaglandins, complement, glucose, insulin, and endorphins.

Other factors involved in secreting these substances include the type of anesthetic used and decreased renal and hepatic function leading to decreased clearance from the kidneys and liver.

The lung normally is responsible for metabolizing and clearing many of these hormones, particularly catecholamines.

Effects of Cardiopulmonary BypassCardiac effects

Studies on immature animal hearts have demonstrated conflicting data with regard to the relative sensitivity of the neonatal heart to ischemia compared to the adult heart.

Reasons for better tolerance to ischemia in the neonatal heart include

the increased glycolytic capability of the immature myocardium and better preservation of high-energy phosphates because of decreased

levels of 5'-nucleotidase, which catalyzes the breakdown of adenosine monophosphate (AMP) to adenosine.

Conversely, accumulation of lactic acid as a result of anaerobic metabolism has been hypothesized as a cause of ischemic intolerance in the neonatal heart.

Effects of Cardiopulmonary BypassCentral nervous system effects Neurologic injury after routine CPB is uncommon in

neonates, but the risk is increased when deep hypothermic circulatory arrest (DHCA) is required. Although permanent injury is less common, evidence of some neurologic injury is observed in as many as 25% of infants who have undergone DHCA.

Neurologic morbidity includes seizures, strokes, changes in tone and mental status, motor disorders, abnormal cognitive functioning, and postpump choreoathetosis. Areas most vulnerable for ischemic injury include the neocortex, hippocampus, and striatum.

Effects of Cardiopulmonary Bypass

Central nervous system effects Another potential mechanism of brain injury involves

binding of glutamate to the N-methyl-D-aspartate receptor (NMDAR). This binding increases the amount of intracellular calcium and subsequently activates proteases, phospholipases, and deoxyribonucleases (DNAases) and promotes generation of free radicals. The net result of these processes is cell injury, cell death, or both.

Microemboli can be detected in patients on CPB. The long-term effect of these emboli is not well defined.

Effects of Cardiopulmonary BypassPulmonary effects

Lung injury is mediated in one of two ways. Leukocyte and complement activation cause an inflammatory response, or a mechanical effect leads to surfactant loss and atelectasis. These types of dysfunction cause a reduction in static and dynamic compliance, reduced functional residual capacity, and an increased alveolar-arterial (A-a) gradient.

Hemodilution reduces oncotic pressure and causes extravasation of fluid into the lung parenchyma.

CPB activates complement and leukocyte degranulation, causing capillary membrane injury and platelet activation, both of which eventually lead to increased pulmonary vascular resistance.

Effects of Cardiopulmonary BypassRenal effects

CPB leads to production of renin, angiotensin, catecholamines, and antidiuretic hormone. In turn, these substances cause renal vasoconstriction and reduced renal blood flow.

Risk factors for postoperative renal dysfunction include preoperative renal disease, contrast-related renal injury, and profound post-CPB reduction in cardiac output.

In the period following CPB, 8% of patients have acute renal insufficiency as indicated by oliguria and increased creatinine levels.

After spontaneous urine output, diuretics are effective at inducing diuresis and reversing renal cortical ischemia associated with CPB, but their use does not alter the time to recovery of renal function.

Use of Hypothermia

Effect on Metabolic Rate In a patient undergoing CPB, hypothermia helps protect

against injury caused by the compromised substrate supply to tissues resulting from reduced flow.

This protection occurs because of a reduction in metabolic rate and decreased oxygen consumption.

The metabolic rate is determined by enzymatic activity, which in turn depends on temperature.

The decrease in metabolic rate is not the only factor involved in hypothermic protection. The actual safe period of hypothermic CPB is longer than the period predicted by a sole reduction in metabolic activity.

Use of HypothermiaEffect on pH

The effect of hypothermia on pH is mediated by its effect on the ionization constant of water and, therefore, its effect on the ionized-to-nonionized ratio of metabolic substrates.

In ischemia, the intracellular pH decreases because of the accumulation of hydrogen ions. In turn, the accumulation of hydrogen ions causes a decrease in the ratio of ionized-to-nonionized metabolic substrates. Nonionized substrates can cross the cellular membrane and are lost. Hypothermia affects this by decreasing the metabolic rate, then by increasing the ionized-to-nonionized ratio.

In addition, the transformation of a semiliquid cellular membrane to a semisolid membrane is postulated to decrease calcium influx.

Use of Hypothermia

Effect on Central Nervous System The effect of hypothermia on the nervous

system is multifactorial. In addition to decreasing the metabolic rate, hypothermia has been demonstrated to decrease the release of glutamate, which is involved in CNS injury during CPB.

A negative effect of hypothermia on brain function is the loss of autoregulation at extreme temperatures, which makes the blood flow highly dependent on extracorporal perfusion.

Techniques of Hypothermia

Currently, two surgical techniques are used in congenital heart surgery, namely,

Deep hypothermic circulatory arrest (DHCA)

Hypothermic low-flow bypass (HLFB)

Deep Hypothermic Circulatory Arrest DHCA provides excellent surgical exposure by

eliminating the need for multiple cannulas within the surgical field and by providing a motionless and bloodless field.

Surgical technique Initiate the cooling phase prior to institution of

CPB by simple cooling of the operating room environment.

After systemic heparinization and cannulation, initiate CPB.

Monitor body temperature via esophageal, tympanic, and rectal routes.

Deep Hypothermic Circulatory ArrestMechanical Problems Obstruction of the inferior vena cava (IVC) by a

misplaced IVC cannula can lead to increased venous pressure, which causes ascites and decreased perfusion pressure in mesenteric, hepatic, and vascular beds. Monitor infants with ascites for GI tract, renal, and hepatic functioning.

Misplacement of the cannula in the superior vena cava (SVC) can result in increased venous pressure in the cerebral venous system. Subsequent cerebral edema results from inadequate venous drainage and a consequent reduction in cerebral blood flow, potentially resulting in ischemia.

Deep Hypothermic Circulatory ArrestMechanical Problems

Arterial cannula misplacement also can occur. If the cannula inadvertently slips beyond the takeoff of the right innominate artery, preferential perfusion to the left side of the brain can be observed.

Presence of any anomalous systemic-to-pulmonary shunts can lead to shunting of blood away from the systemic circulation, through the pulmonary circuit, and then through the venous cannula to the CPB machine.

Thus, the systemic perfusion is shunted away from the body in a futile circuit back to the CPB machine. Anatomic lesions where such shunting can occur include an unrecognized patent ductus arteriosus and large aortopulmonary collaterals as found in pulmonary atresia.

Deep Hypothermic Circulatory ArrestInflammatory response Activation of the inflammatory pathway leads to serious

complications, morbidity, and mortality. Several strategies have been used to modify the inflammatory response. These include:

Use of heparin-coated CPB circuit to reduce the inflammatory response

Modifying the blood cardioplegia solution has been investigated as a means of reducing inflammatory-mediated myocardial injury after intracardiac repair.

Since neutrophils may mediate the local inflammatory response in the heart, a leukocyte-depleted blood cardioplegia (LDBC) has been postulated as a means for improving myocardial protection during CPB.

Modified ultrafiltration.

Anticoagulation for Cardiopulmonary BypassAnticoagulation and heparin reversal Paediatric and neonatal patients undergoing CPB for

cardiac surgery are prone to coagulopathy in the early postoperative period.

Contributing factors include hemodilution, immaturity of the coagulation system, depletion of platelets and other hemostatic proteins, and the complex nature of the operations performed, which

often include multiple suture sites and, therefore, an increased number of potential bleeding sites.

Anticoagulation for Cardiopulmonary BypassAnticoagulation To avoid forming thrombi in the CPB machine, heparin is

administered prior to cannulation. Heparin is chosen because it is a fast-acting anticoagulant and its action can be inhibited rapidly by protamine.

Heparin activates antithrombin III, which inhibits thrombin activity.

Heparin can be stored in the vascular endothelium and smooth muscle, contributing to heparin rebound, which is observed after discontinuation of CPB and heparin reversal.

Clearance of heparin also is determined by hepatic and renal function.

Anticoagulation for Cardiopulmonary BypassAnticoagulation Typically, a loading dose of 200-300 U/kg of heparin is

given and then heparin activity is monitored by measuring activated clotting time (ACT) and heparin levels.

Physicians at some centers administer 300 U/kg, check to see if this leads to an ACT of 450-480 seconds, then administer supplemental heparin based on subsequent ACT levels.

The use of only one of these monitoring methods may not reflect the full degree of anticoagulation.

ACT levels can be affected by factors unrelated to heparin concentration, including the patient's hematocrit and temperature.

Anticoagulation for Cardiopulmonary Bypass

Heparin reversal Protamine binds to heparin and releases antithrombin III.

One method of administering protamine is to administer 1-1.3 mg for each 100 U of heparin administered. This method does not take into account the half-life of heparin or its clearance from circulation.

Other methods include ACT-heparin dose-response curves, direct measurement of heparin levels, and use of the heparin-protamine titration.

Anticoagulation for Cardiopulmonary Bypass

Adverse effects of protamine Release of histamine, which can lead to a decrease in

systemic vascular resistance

True anaphylaxis, which is mediated by antiprotamine immunoglobulin E (IgE) and observed primarily in patients with prior exposure to protamine (e.g. neutral protamine Hagedorn [NPH] insulin) and in patients with fish allergy

Thromboxane release, which leads to pulmonary vasoconstriction and bronchoconstriction

Anticoagulation for Cardiopulmonary BypassStrategy to counteract post-CPB bleeding Bleeding after CPB is not unusual. Identify any sources of obvious surgical bleeding since

this is the most common cause of post-CPB bleeding. Assess the adequacy of the protamine dose. If the dose appears to be sufficient, the next most common

cause of bleeding is platelet dysfunction, and platelet infusion is warranted, even if the platelet count is within reference range. Often, platelets are dysfunctional after CPB in infants and children.

Administration of aprotinin can decrease blood transfusion requirements in patients undergoing repeat surgeries and in patients who are cyanotic.

Desmopressin has antifibrinolytic activity and acts as a kallikrein inhibitor. Mild hypersensitivity reactions and anaphylactic reactions are reported.

Hypothermic Low-Flow Cardiopulmonary Bypass The finding that DHCA was associated with neurologic

morbidity has led researchers to investigate the use of HLFB.

This technique allows continuous low-flow perfusion to the organs during the operation, which may lead to an increase in oxygen supply, better nutrient supply, and better achievement of homogeneous hypothermia during bypass.

Recent trials comparing the 2 methods have reported lower rates of neural dysfunction in the group of patients undergoing HLFB.