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Chapter: Clinical Anesthesiology: Anesthetic Management: Anesthesia for Cardiovascular Surgery

Physiological Effects of Cardiopulmonary Bypass

Initiation of CPB is associated with a variable increase in stress hormones and systemic inflammatory response.


Hormonal, Humoral, & Immunological Responses

Initiation of CPB is associated with a vari-able increase in stress hormones and systemicinflammatory response. Elevated levels of catechol-amines, cortisol, arginine vasopressin, and angioten-sin are observed. These neurohormonal responses are variously influenced by depth of anesthesia, blood pressure, type of surgical repair, or presence of pulsatile CPB.

Multiple humoral systems are also activated, including complement, coagulation, fibrinolysis, and the kallikrein system. Contact of blood with the internal surfaces of the CPB system activates complement via the alternate pathway (C3) as well as the classic pathway; the latter also activates thecoagulation cascade, platelets, plasminogen, and kallikrein. Mechanical trauma from blood contact with the bypass apparatus also activates platelets and leukocytes. Increased amounts of oxygen-derived free radicals are generated. A systemic inflammatory response syndrome similar to that seen with sep-sis and trauma can develop. When this response is intense or prolonged, patients can develop the same complications, including generalized edema, the acute respiratory distress syndrome, coagulopathy, and acute kidney failure.

CPB alters and depletes glycoprotein receptors on the surface of platelets. The resulting platelet dys-function likely increases perioperative bleeding and potentiates other coagulation abnormalities (activa-tion of plasminogen and the inflammatory response described above).

Animal and clinical research has demon-strated that the inflammatory response to CPB can be modulated by various therapies. Leukocyte depletion reduces inflammation and may similarly reduce complications. Leukocyte-depleted blood cardioplegia has been shown to improve myocar-dial preservation in some studies. Hemofiltration (ultrafiltration) during CPB, which presumably removes inflammatory cytokines, appears beneficial in pediatric patients. Administration of free radical scavengers such as high-dose vitamins C and E and mannitol has improved outcome in some studies. Systemic corticosteroids before and during CPB can modulate the inflammatory response during CPB but improved outcome is not well established. Two large randomized clinical trials are underway to test whether there is an outcome benefit to the routine use of systemic corticosteroids with CPB.

One once-promising agent, aprotinin, reduced inflammation and surgical bleeding following CPB. Unfortunately, it increased mortality and is no lon-ger available in North America.

CPB Eects on Pharmacokinetics

Plasma and serum concentrations of most water-soluble drugs (eg, nondepolarizing muscle relax-ants) acutely decrease at the onset of CPB, but the change can be minimal and inconsequential for most lipid-soluble drugs (eg, fentanyl and sufen-tanil). The effects of CPB are complex because of the sudden increase in volume of distribution with hemodilution, decreased protein binding, and changes in perfusion and redistribution between peripheral and central compartments. Some drugs, such as opioids, also bind CPB components (but this is also minimal and inconsequential). Heparin potentially alters protein binding of drugs and ions by releasing and activating lipoprotein lipase, which hydrolyzes plasma triglycerides into free fatty acids; the latter can competitively inhibit drug binding to plasma proteins and bind free calcium ions. With the possible exception of propofol, constant infusion of a drug during CPB (even when adjusted to main-tain a constant “effect site” concentration using data from patients not undergoing CPB) generally causes progressively increasing blood levels as a result of reduced hepatic and renal perfusion (reduced elimi-nation) and hypothermia (reduced metabolism). 

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Clinical Anesthesiology: Anesthetic Management: Anesthesia for Cardiovascular Surgery : Physiological Effects of Cardiopulmonary Bypass |

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