Cardiopulmonary bypass
Cardiopulmonary bypass (CPB) is a technique that temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and the oxygen content of the body.  The CPB pump itself is often referred to as a Heart-Lung Machine or the Pumper.  Cardiopulmonary bypass pumps are operated by allied health professionals known as Perfusionists in association with surgeons who connect the pump to the patient's body.  CPB is a form of extracorporeal circulation.

# Uses of cardiopulmonary bypass
Cardiopulmonary bypass is commonly used in heart surgery because of the difficulty of operating on the beating heart.  Operations requiring the opening of the chambers of the heart require the use of CPB to support the circulation during that period.
CPB can be used for the induction of total body hypothermia, a state in which the body can be maintained for an hour or more without perfusion (blood flow).  If blood flow is stopped at normal body temperature, permanent brain damage normally occurs in three to four minutes  death may follow shortly afterward.
ECMO is a simplified form of CPB sometimes used as life-support for newborns with serious birth defects, or to oxygenate and maintain recipients for organ transplantation until new organs can be found.

## Surgical procedures in which cardiopulmonary bypass is used
- Coronary artery bypass surgery
- Cardiac valve repair and/or replacement (aortic valve, mitral valve, tricuspid valve, pulmonic valve)
- Repair of large septal defects (atrial septal defect, ventricular septal defect, atrioventricular septal defect)
- Repair and/or palliation of congenital heart defects (Tetralogy of Fallot, transposition of the great vessels)
- Transplantation (heart transplantation, lung transplantation, heart-lung transplantation)
- Repair of some large aneurysms (aortic aneurysms, cerebral aneurysms)
- Pulmonary thromboendarterectomy
- Pulmonary thrombectomy

# History
Dr. Clarence Dennis led the team that conducted the first known operation involving open cardiotomy with temporarary mechanical takeover of both heart and lung functions on April 5, 1951 at the University of Minnesota Hospital.  The patient did not survive due to an unexpected complex congenital heart defect.  This followed four years of laboratory experimentation with dogs.
John Gibbon is credited with developing the first truly practical heart-lung bypass machine; he performed the first successful surgery with it on May 6, 1953 in Philadelphia, an atrial septal defect repair. But although he is accredited with the invention, many suspect that he was not awarded the Nobel Prize for it because of his failure to mention the other members of the team working with him. Other surgeons such as Bernard J. Miller, a young doctor at the time, created many of the pieces that make the machine function.

# Components of cardiopulmonary bypass
Cardiopulmonary bypass consists of two main functional units, the pump and the oxygenator which remove oxygen deprived blood from a patients body and replace it with oxygen-rich blood through a series of hoses.

## Tubing
The components of the CPB circuit are interconnected by a series of tubes made of silicone rubber, or PVC.  The tubing in the CPB circuit is similar to transparent garden hose.

## Pumps

### Roller pump
The pump console usually comprises several rotating motor-driven  pumps that peristaltically "massage"  tubing .  This action gently propels the blood through the tubing. This is commonly referred to as a roller pump, or peristaltic pump.

### Centrifugal pump
Many CPB circuits now employ a centrifugal pump for the maintenance and control of blood flow during CPB.  By altering the speed of revolution (RPM) of the pump head, blood flow is produced by centrifugal force.  This type of pumping action is considered to be superior to the action of the roller pump by many because it is thought to produce less blood damage (Hemolysis, etc.).

## Oxygenator
The oxygenator is designed to transfer oxygen to infused blood and remove carbon dioxide from the venous blood.  Cardiac surgery was made possible by CPB using bubble oxygenators, but membrane oxygenators have supplanted bubble oxygenators since the 1980s.
The oxygenator was first conceptualised in the 17th century by Robert Hooke and developed into practical extracorporeal oxygenators by French and German experimental physiologists in the 19th century. Bubble oxygenators have no intervening barrier between blood and oxygen, these are called 'direct contact' oxygenators. Membrane oxygenators introduce a gas-permeable membrane between blood and oxygen that decreases the blood trauma of direct-contact oxygenators. Much work since the 1960s focused on overcoming the gas exchange handicap of the membrane barrier, leading to the development of high-performance microporous hollow-fibre oxygenators that eventually replaced direct-contact oxygenators in cardiac theatres.
Another type of oxygenator gaining favour recently is the heparin-coated blood oxygenator which is believed to produce less systemic inflammation and decrease the propensity for blood to clot in the CPB circuit.

## Cannulae
Multiple cannulae are sewn into the patient's body in a variety of locations, depending on the type of surgery.  A venous cannula removes oxygen deprived blood from a patients body.  An arterial cannula is sewn into a patient's body and is used to infuse oxygen-rich blood.  A cardioplegia cannula is sewn into the heart to deliver a cardioplegia solution to cause the heart to stop beating.

## Cardioplegia
A CPB circuit consists of a systemic circuit for oxygenating blood and reinfusing blood into a patient's body (bypassing the heart); and a separate circuit for infusing a solution into the heart itself to produce cardioplegia (i.e. to stop the heart from beating), and to provide myocardial protection (i.e. to prevent death of heart tissue).

# Operation
A CPB circuit must be primed with fluid and all air expunged before connection to the patient.  The circuit is primed with a crystalloid solution and sometimes blood products are also added. The patient must be fully anticoagulated with an anticoagulant such as heparin to prevent massive clotting of blood in the circuit.

# Myocardial Protection and Cardiopulmonary Bypass

## 1. Myocardial Perfusion
A. Normally, subendocardial flow exceeds subepicardial flow
B. Myocardial perfusion, however, is altered by cardiopulmonary bypass
C. Narrow pulse pressure and variable mean pressure affects coronary perfusion pressure
D. Wall tension is increased in the empty, smaller heart
E. Ventricular fibrillation also increases wall tension
F. Regulatory and inflammatory factors are released which affect coronary resistance
G. Microemboli from the circuit and hemodilution impair oxygen delivery
H. Endothelial and myocardial edema further affect perfusion
I. Subendothelial vulnerability is increased by hypertrophy, coronary disease, fibrillation, cyanosis, shock, and chronic heart failure
J. The acutely ischemic heart may have poor reflow to the injured area

## 2. Myocardial Ischemic Injury

### A. Acute ischemic dysfunction
1) Global myocardial ischemia
2) Reversible contractile failure, mostly from change in perfusion pressure
3) Immediate recovery as oxygen supply is restored

### B. Stunning
1) Reversible systolic and diastolic dysfunction, no myocardial necrosis
2) Begins in subendothelium and progresses outward
3) May be accompanied by endothelial dysfunction
4) Results from ischemia-reperfusion insult, mediated by increased intracellular calcium accumulation
5) Recovery occurs within hours to weeks

### C. Hibernation
1) Reversible chronic contractile depression
2) Related to poor myocardial blood flow
3) Recovery occurs within weeks to months

### D. Necrosis
1) Irreversible ischemic injury with myocardial necrosis
2) Hypercontracture occurs first in the subendothelium and is more rapid in the hypertrophied heart
3) Typically results in contraction band necrosis, rarely "stone heart"
4) Osmotic and ionic dysregulation produce membrane injury and myocyte lysis

## 3. Cardioplegia
A. Studies in animals have inconsistent correlation with clinical results due to species differences, extent of disease, and perioperative events that 
precipitate, extend, or enhance myocardial damage
B. The goals of cardioplegia are to protect against ischemic injury, provide a motionless and bloodless field, and allow for effective post-ischemic myocardial resuscitation
C. Cardioplegic techniques vary according to perfusate (blood vs. crystalloid), duration (continuous vs. intermittent), route (antegrade vs. retrograde), temperature (warm vs. cold), and additives
D. Special consideration is required for the acutely ischemic heart and the neonate

## 4. Mechanisms of Cardioplegic Protection
A. Mechanical arrest (potassium-induced) will reduce oxygen consumption by 80%
B. Hypothermia will reduce consumption by another 10-15%
C. Aerobic metabolism can be maintainted with oxygenated cardioplegia
D. Hypothermic arrest is sustained with readministration every 15-30 minutes
E. Retrograde delivery protects the left ventricle more completely than the right ventricle
F. Prevent myocardial rewarming with systemic hypothermia, aortic and ventricular vents, and caval occlusion
G. In acute ischemia, use warm induction with substrate enhancement (glutamate, aspartate)
H. Reperfusion should be controlled, using warm, hypocalcemic alkaline cardioplegia
I. This approach combats intracellular acidosis and rapid calcium infusion injury
J. Retrograde or low-pressure antegrade perfusion is preferred for reperfusion
K. Ensure uniform warming

## 5. Neonates and Children
A. Children older than 2 months have similar myocardial physiology to adults
B. The neonatal myocardium, however, is different in several ways
C. Hypoxia is more easily tolerated
D. There are greater glycogen stores and more amino acid utilization
E. ATP breakdown is slower due to deficiency in 5' nucleotidase
F. Multidose cardioplegia is disadvantageous
G. Cyanosis may worsen resistance to ischemia
H. Amino acid substrate enhancement is beneficial

## 6. Cardioplegia Composition
A. Blood has the advantage of oxygen carrying capacity, histidine and hemoglobin buffers, free radical scavengers in RBCs, and metabolic substrates
B. Blood also has improved rheologic and oncotic properties, which may lessen myocardia edema
C. Buffers such as THAM, histidine, and NaHCO3 form a slightly alkaline solution for reperfusion that can counteract intracellular acidosis
D. Small amounts of calcium (0.1-0.5 mM/L) restores calcium that has been chelated by citrate
E. Potassium concentrations range from 10-25 mM/L, with the first dose being the highest
F. Other substrates are being evaluated, including allopurinal, SOD, deferoxamine, adenosine, nucleoside transport inhibitors, and potassium-channel openers

# Cardiopulmonary Bypass

### 1. The Circulatory Environment
A. Cardiopulmonary bypass is an abnormal circulatory state
B. Non-pulsatile flow, hemolysis, hemodilution, foreign surface exposure, general stress response, and the inflammatory response all contribute
C. Mechanial components
1) Roller pumps are slightly non-occlusive, resistance-independent, and may cause less blood trauma
2) Centrifugal pumps are dependent on inflow or outflow resistance; will cease flow at very low inflow resistance and very high outflow resistance
3) Venous drainage can be active or siphoned
4) Active drainage requires vacuum through the venous reservoir or negative pressure from the pump
B. Heat exchanger
1) The cooling or warming gradient is usually within 10-14 degrees of the patient's temperature
2) This minimizes the tendency for gas to come out of solution and risk of air embolism
3) Mixed blood temperature should be less than or equal to 38.5C
4) The water bath should stay between 15 and 42C to prevent organ damage (too cold) and hemolysis (too warm)
C. Oxygenator
1) Largest foreign surface contact area
2) Membrane oxygenators can be microporous, hollow fiber, or silastic (true membrane)
3) Gas flow is titrated to maintain PaO2 between 85 and 250mmHg to avoid O2 toxicity
4) PCO2 is regulated by gas and blood flow through the membrane
5) pH is controlled by adjusting the PaCO2
6) alpha stat adjusts the pH to 37C, with the goal of providing optimal enzymatic function during hypothermia
7) pH stat corrects the pH to the temperature of the patient's blood, with the goal of relative hypercarbia to increase cerebral blood flow

### 2. Mechanisms of Injury
A. Mechanical
1) The foreign surfaces of the bypass circuit (boundary layer of oxygenator, heat exchanger, filters, tubing) interact with the blood
2) Shear stresses include the pump, cardiotomy suction, and cannulae
3) Microemboli can form as particles from the oxygenator, platelet aggregate, or fibrin aggregates, and are greatest within the first 15 minutes of bypass
B. Humoral
1) Factor XII (Hageman factor), the alternative complement cascade (C3a), kallekrein, and plasminogen are activated in various degrees
2) Other factors interrelate and amplify the inflammatory reaction, including the arachidonic acid cascade, interleukins, TNF, and PAF
C. Cellular
1) Neutrophils play a major role in humoral activation and are sequestered in the lung, releasing cytotoxin and free radicals which increase 
vasoreactivity and vascular permeability
2) Monocytes and mast cells also participate, although their role is unclear
3) Lymphocytes have a minor role, if any
4) Platelets are activated and elaborate GPIB, IIB, and IIIA
5) Absolute number of platelets is reduced by 40% by the end of bypass, and the number of receptors is also decreased
6) Endothelial cells are affected by abnormal flow, humoral factors, and local ischemia
7) A wide variety of substances are expressed by the endothelium, including prostaglandins, thromboxanes, leukotrienes, and interleukins

### 3. Miscellaneous
A. Circulatory arrest with profound hypothermia (18-20C) is generally safe up to 45 minutes
B. Over 60 minutes is associated with increased incidence of neurologic deficit
C. The period between 45 and 60 minutes is unclear, as histologic injury seems to be greater than functional injury
D. Maintain a gradient of 4-6C, as rapid cooling produces uneven cerebral cooling
E. Retrograde and low flow cerebral perfusion are currently being evaluated
F. Pulsatile flow has not been shown to be superior to non-pulsatile flow
G. Lower ACT of 300-350 seconds is not associated with greater complications compared to standard ACT of 450
H. Aprotinin will elevate the ACT (600-800), neutralizes the kallikrein cascade, and protects platelet receptors
I. Protamine reactions occur through the classical component pathway and cause direct myocardial depression

# Complications
CPB is not benign and there are a number of associated problems:
- Postperfusion syndrome (also known as Pumphead)
- Hemolysis
- Capillary Leak Syndrome
- Clotting of blood in the circuit - can block the circuit (particularly the oxygenator) or send a clot into the patient.
- Air embolism
- Leakage - a patient can rapidly exsanguinate (lose blood perfusion of tissues) if a line becomes disconnected.