Incidence of adverse neurologic / psychiatric disturbances following CPB is approximately 6% [Roach GW et al. N Engl J Med 335: 1857, 1996], although there is some data to suggest that over the long term the incidence is no different than in patients treated non-surgically, but is rather a function of the natural history of HTN, atherosclerosis, etc. [Selnes OA et al. Ann Neurol 63: 581, 2008]
It is important to note that during adult, moderately-hypothermic, alpha-stat CPB, the major effectors of CBF are temperature, anesthetic depth, CMRO2, and PaCO2. Mean arterial pressure is completely unrelated to CBF over a range of approximately 30 – 110 mm Hg during CPB [Govier AV et al. Ann Thorac Surg 38: 592, 1984].
Major Effectors of CBF During CPB (moderate hypothermia, alpha-stat, adults) 1. Temperature 2. Anesthetic Depth 3. CMRO2 4. PaCO2
Pump flow has almost no effect on CBF, nor does pump character (pulsatile versus constant) [Schell RM et al. Anesth Analg 76: 849, 1993]
While surgical and anesthetic decisions may lead to myocardial injury, it is thought that the predominant source of myocardial injury during CPB is inadequate myocardial protection. It is thought that inadequate protection leads to phosphate depletion and an inability of myocytes to transport calcium out of the cell, thus leading to intracellular calcium accumulation. Unprotected aortic cross clamping can be particularly dangerous, and if an aortic cross-clamp is placed, cessation of electrical and mechanical function should be achieved as quickly as possible
According to Kaplan [Kaplan JA, ed. Essentials of Cardiac Anesthesia. Saunders, 2008 p 522 (ISBN 978-1-4160-3786-6)], there are four phases of myocardial protection:
Phases of Myocardial Protection [Kaplan, 2008] 1. Pre-arrest preparation 2. Arrest interval 3. Reperfusion
According to Kaplan, the anesthesiologist is responsible for Phase I and should prepare the heart for ischemia by correcting fluid deficits and providing sufficient glucose. This assertion is supported by small amounts of animal data [Butchart EG et al. J Thorac Cardiovasc Surg 79: 812, 1980], as well as two human studies examining the use of glucose insulin potassium (GIK) therapy in patients undergoing CPB [Rudez I et al. Lijec Vjesn 117 S2: 105, 1995; Quinn DW et al. J Thorac Cardiovasc Surg 131: 34, 2006]. While the largest study to date (Quinn DW et al., RCT, 260 patients) suggests a benefit, not all data support the administration of glucose pre-CPB [Bruemmer-Smith S et al. Br J Anaesth 88: 489, 2002; FREE Full-text at British Journal of Anaesthesia]
While the anesthesiologist can do little to protect the heart during Phase II, Kaplan suggests that immediate TEE examination after initiation of CPB can assist in diagnosing ventricular overdistention [Kaplan JA, ed. Essentials of Cardiac Anesthesia. Saunders, 2008 p 522 (ISBN 978-1-4160-3786-6)], which will adversely affect myocardial perfusion/protection during Phase II
Besides sequestering extravascular fluid and PMNs, the lungs have several metabolic functions which are perturbed by CPB, namely metabolism of norepinephrine (which ceases during full CPB) and sequestration of opioids (which are re-released following reperfusion). Optimal pulmonary strategies surrounding CPB (ex. FiO2, PEEP, tidal volumes, PCV vs. VCV) have not been defined
The incidence of renal failure following CPB may be as high as 30%, depending on the definition used. Renal failure in the setting of CPB increases mortality significantly [Huffmyer JL et al. J Cardiothorac Vasc Anesth 23: 468, 2009]. Note that urine output is not correlated with the incidence of renal failure. The key to maintenance of adequate renal blood flow is relatively low regional vascular resistance (i.e. increasing RVR less than SVR) [Aronson S and Blumenthal RJ. Cardiothorac Vasc Anesth 12: 567, 1998]. Perioperative use of statins [Huffmyer JL et al. J Cardiothorac Vasc Anesth 23: 468, 2009] and fenoldopam [Landoni G et al. J Cardiothorac Vasc Anesth 22: 27, 2008] may modify the risk of perioperative renal failure, although both pharmacologic strategies require further investigation before widespread adoption
Splanchnic hypoperfusion is thought to lead to translocation of gut bacteria and transient endotoxemia following CPB
Massive stress response (epinephrine levels increase 9-fold, vasopressin levels increase 20-fold). Some patients will develop the sick euthyroid syndrome (lowered levels of T3 and T4 despite normal levels of TSH), which appears to occur with patients undergoing off-pump cardiac surgery as well [Velissaris T et al. Eur J Cardiothorac Surg 36: 148, 2009]. Of note, there is at least one randomized, controlled trial (n = 170) suggesting that T3 lowers vasopressor requirements and the incidence of mechanical device placement following CPB [Mullis-Jansson SL et al. J Thorac Cardiovasc Surg 117: 1128, 2009]
The complement system (alternative pathway via contact with foreign surfaces, classical pathway via heparin-protamine complexes, both pathways via endotoxin) is activated, as are the coagulation (by Factor XII), fibrinolytic, and kallikrein-bradyknin systems. CPB leads to a variation of the Systemic Inflammatory Response Syndrome (SIRS). The inflammatory response to reperfusion is implicated in the reperfusion injury. Transient endotoxemia occurs following CPB, most likely related to splanchnic hypoperfusion and resultant translocation of gut bacteria. Both endotoxin and cytokines lead to upregulation of iNOS, an agent which is implicated in post-CPB vasoplegia [Laffey JG et al. Anesthesiology 97: 215, 2002; FREE Full-text at Anesthesiology]. In the face of iNOS-induced vasoplegia, treatment with Methylene Blue (an inhibitor of guanylate cyclase, as well as both endogenous and inducible nitric oxide synthase) can lead to profound hemodynamic improvement
Other inflammatory mediators implicated in organ dysfunction following CPB (but for which there are currently no available clinical therapies) include leukotrienes (which are vasoconstrictors), platelet activating factor, tissue factor, thrombin (the most potent activator of platelets during CPB), thromboxane A2 (decreased), prostaglandins, prostacyclins, matrix metalloproteines, and endothelins. Inhibitors for platelet activating factor (data both in favor [Langley SM et al. Ann Thorac Surg 68: 1578, 1999] and out of favor [Taggart DP et al. Heart 89: 897, 2003]) and endothelin-1 [Toole JM et al. J Thorac Cardiovasc Surg 139: 646, 2010] may be under development
A relatively novel concept in the field of immunology (primarily from the infectious disease literature) is the “sepsis seesaw” [Hotchkiss RS et al. Nat Med 15: 496, 2009 (Hotchkiss interview with OpenAnesthesia in our Audio/Video section)], also known as the Counter Anti-Inflammatory Response Syndrome (CARS), in which an organism overcompensates for an increase in immunological activity by shutting down, effectively leading to a dangerous immunosuppresive state, which may have implications for patients undergoing cardiopulmonary bypass [Ziegeler S et al. Scand J Immunol 69: 234, 2009].