<<

. 5
( 8)



>>

a membrane oxygenator or hemofilter can be spliced into the system. Although patients sup-
ported with the CentriMag are kept on the intensive care unit, they can be allowed to move
around the bed space and can undergo physiotherapy. Because of its simplicity and versatility,
the CentriMag is becoming rapidly adopted by many cardiothoracic centers.

Thoratec PVAD and IVAD
The Thoratec system was originally designed as a pulsatile paracorporeal ventricular
assist device (PVAD), which can be used for either left, right or biventricular support (see
Figure 9.2). The pump unit consists of a polyurethane blood sac and Bjork-Shiley monostrut
inflow and outflow mechanical valves, inside a rigid polysulfone case (see Figure 9.6). A range
of inflow cannulae allow either left or right atrial or ventricular cannulation. The outflow can-
nula can be attached to the ascending aorta or the pulmonary artery. The inflow and outflow
cannulae are passed across the abdominal wall and the pump unit rests in front of the abdo-
men. The VAD is connected to an external pneumatic drive console via a gas line and can
provide pulsatile support of up to 6.5 l/minute.


Figure 9.3 Levitronix CentriMag
Primary Console and patient.




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Chapter 9: Mechanical circulatory support



Figure 9.4 Levitronix
CentriMag Pump, Motor and
Primary Drive Console.




Figure 9.5 Example of BiVAD
cannulation with the LVAD inflow
cannula in the LV apex and the
outflow cannula returning blood
to the ascending aorta. The RVAD
inflow cannula takes blood from
the right atrium with the outflow
cannula returning blood to the
pulmonary artery. The cannulae
are tunneled through the skin to
allow for chest closure.




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Chapter 9: Mechanical circulatory support



Figure 9.6 The cutaway view
shows the internal components
of the PVAD. Blood passes from
a percutaneous inflow cannula,
through a mechanical tilting disc
valve that maintains unidirec-
tional flow, and into the poly-
urethane blood sac. On exertion
of drive pressure, blood is forced
out of the VAD through another
mechanical valve and into the
outflow cannula, to return to the
patient.




Figure 9.7 Thoratec IVAD with its streamlined
titanium housing and velour-coated percutaneous
lead.




More recently, Thoratec has taken the PVAD design and adapted it into an implantable
ventricular assist device (IVAD) by substituting the polysulfone case with a more stream-
lined titanium housing (see Figure 9.7). Along the lines of the PVAD, the Thoratec IVAD can
be used as left or right ventricular support as well as biventricular support using two com-
plete units. This implantable version makes the system much more acceptable for the patients
and their carers (see Figure 9.8) and it is currently the only implantable VAD that can provide
support for either ventricle.


HeartMate II
The HeartMate II is a high-speed, axial flow blood pump. It is a compact device weighing
400 g and measuring approximately 4 cm in diameter and 6 cm long and, as such, it may
be suitable for a wider range of patients, including small adults and children.
The internal pump surfaces are a smooth, polished titanium. A rotor within the pump
contains a magnet and is rotated by the electromotive force generated by the integral magnetic
motor (see Figure 9.9). The rotor spins on blood-lubricated ceramic bearings, and propels the
blood from the inflow cannula sited in the LV apex to the ascending aorta. The pump speed
can vary from 6000 to 15 000 rpm, providing blood flow of up to 10 l/minute.
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Chapter 9: Mechanical circulatory support



Figure 9.8 Patient support with two IVADs mobilizing
with the Thoratec portable TLC-II driver.




Figure 9.9 Cutaway view of
HeartMate II showing inflow
cannula in the left ventricle, rotor,
magnetic motor and ceramic
bearings, and outflow towards
ascending aorta.




The pump can run in two operating modes: fixed speed and auto-speed. In fixed-speed
mode, the device operates at a constant speed, which can be adjusted via the system monitor.
In the auto-speed mode, the pump speed varies in response to different levels of patient or
cardiac activity.
External equipment includes a system controller, power base unit, system monitor,
rechargeable batteries and battery clips. The system controller continuously monitors and
controls the implanted pump and shows information regarding alarm conditions.
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Chapter 9: Mechanical circulatory support




Figure 9.10 Diagram of the configuration of the HeartMate II showing implanted pump, percutaneous lead,
external system controller and batteries.



Figure 9.11 Ventracor VentrAssist.




The power base unit serves as a battery charger and an interface between the system moni-
tor and the implanted pump. The 20-foot power cable allows the system to be operated by AC
power. Alternatively, patients can connect to batteries, which permits the system to be oper-
ated tether-free for 3“5 hours (see Figure 9.10).
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Chapter 9: Mechanical circulatory support



Figure 9.12 Inflow to the VentrAssist is from the LV
apex and outflow to the ascending aorta. The percu-
taneous driveline is tunneled out through the skin.
Despite being a continuous flow device, some pulsatil-
ity of flow may be detectable with native ventricular
contractions.




Figure 9.13 Ventracor™s compact backpack containing
controller and batteries.




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Chapter 9: Mechanical circulatory support




Ventracor VentrAssist
The VentrAssist is one of the latest generations of longer term LVADs consisting of a small
implantable titanium centrifugal pump (see Figures 9.11, 9.12, 9.13), percutaneous driveline,
portable controller and rechargeable battery packs. When activated, the impeller is hydrody-
namically suspended on a thin film of blood and requires no conventional bearing. By elimi-
nating the potential for mechanical wear and tear, these pumps are designed for maximum
durability. Continuous flow devices tend to be smaller in size than pulsatile devices, and are
quiet in operation, making them less intrusive to live with. It is hoped that these devices can
provide long-term circulatory support with lower morbidity and mortality.


VAD patient management
Preoperative management
Patients requiring a VAD implant are probably amongst the sickest patients to undergo car-
diac surgery. They have severe heart failure and are either in impending or established end-
organ failure. A low cardiac output state coupled with systemic venous congestion result in
compromised organ perfusion. The kidneys become refractory to diuretic therapy and hepatic
dysfunction manifests as coagulation abnormalities. The lungs are stiff from pulmonary con-
gestion, increasing the work of breathing, and many patients are grossly fluid overloaded.
If the stability of the patient permits, a period of preoperative optimization in the ICU
prior to VAD implant can be highly beneficial. Inotropic therapy should be rationalized to
reduce the risk of arrhythmias and a period of IABP support helps augment end-organ per-
fusion. Furthermore, the IABP reduces left atrial pressure, thereby reducing the work of the
right ventricle indirectly. Low-dose vitamin K can normalize an elevated prothrombin time,
which in turn reduces the risk of perioperative hemorrhage.
Continuous veno-venous hemofiltration (CVVH) is the most expeditious way of reduc-
ing excessive intravascular volume and total body water content. Patients with chronic heart
failure with CVP >20 mmHg are often grossly edematous. The aim is to normalize the preload
and bring the CVP towards 10“12 mmHg. In practice, CVVH can be used to give a negative
balance of 600“1000 ml per hour until the target CVP is reached. In these patients, it is not
uncommon to remove 7“10 l of fluid in the first 24 hours of CVVH. As the venous pressure
begins to normalize, excessive fluid from the third spaces also returns to the intravascular
compartment and peripheral edema resolves. Finally, by normalizing an elevated preload,
the overstretched ventricles and atrio-ventricular valves are allowed to return to more physi-
ological dimensions, often resulting in improvements in function of the atrio-ventricular
valves.
The combined use of IABP and CVVH support in fluid overloaded patients in a low car-
diac output state often results in augmentation of cardiac output and tissue oxygen delivery,
as measured by improvements in mixed venous oxygen saturations.

Perioperative management
The perioperative strategy should be aimed at minimizing further insult to these sick patients
during VAD implantation, targeting those areas that are known to result in serious morbidi-
ties and mortality. Perhaps the most unpredictable and dangerous complication following
LVAD implantation is right ventricular failure. It is therefore imperative to pay particular
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Chapter 9: Mechanical circulatory support



Table 9.7. Factors contributing to right ventricular failure following LVAD

Right ventricular dysfunction
· Right ventricular ischemia
· Deviation of the interventricular septum to the left
· Air embolism into the right coronary artery
· Right ventricular volume overload and overdistension
Functional regurgitation of tricuspid valve
Elevated pulmonary vascular resistance
· Atelectasis
· Metabolic acidosis
· Pulmonary vasospasm



Table 9.8. Perioperative LVAD patient management

Broad-spectrum prophylactic antibiotics and antifungal agents
Trans-esophageal echocardiography
· Confirm aortic valve competence
· Exclude patent foramen ovale and ASD
· Confirm de-airing
· Check LVAD cannula position
· Confirm decompression of LA and LV during LVAD support
· Monitor right ventricular and tricuspid valve function when weaning from CPB
Normothermic cardiopulmonary bypass
Continuous ventilation of the lungs with nitric oxide at 10 ppm
Filtration on CPB and maintain
· Hb >10 g/dl
· Base excess ± 2 mEq
No aortic cross-clamp during VAD cannulae implant
Pericardial CO2
Dopamine infusion at 5 μg/kg/minute or appropriate inotropic support for right ventricle
Vasopressin infusion for SVR


attention to factors that might contribute to this complication (see Table 9.7). The other com-
monly encountered problem is early postoperative hemorrhage.
The VAD implant procedure should be covered by broad-spectrum prophylactic antibi-
otics and antifungal agents. Trans-esophageal echocardiography (TOE) is used to confirm
aortic valve competence and exclude the presence of a patent foramen ovale or an atrial septal
defect. If present, they require surgical closure at the time of VAD implant, in order to pre-
vent a right to left shunt following decompression of the left-sided chambers with an LVAD.
The lungs can be kept ventilated throughout the bypass period with the addition of nitric
oxide at 10 parts per million (ppm) to minimize atelectasis and pulmonary vasoconstric-
tion, respectively. We advocate normothermic cardiopulmonary bypass using hemofiltration
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Chapter 9: Mechanical circulatory support



(ultrafiltration) to help maintain hemoglobin >10 g/dl and base excess within ±2 mEq/l. The
VAD cannulae are implanted into a beating heart, avoiding aortic cross-clamping and cardiac
ischemia. The pericardial space is flooded with carbon dioxide so that gas bubbles entrained
into cardiac chambers can dissolve more readily. The right ventricle is supported with an
infusion of dopamine at 5 μg/kg/minute. The heart rate is optimized with temporary pacing
at 90“100 bpm. Systemic vascular resistance is maintained between 800 and 1000 dyn.s/cm5
using an infusion of vasopressin or with an alpha-agonist. Thorough de-airing of the heart is
confirmed with TOE before finally attempting to wean from bypass.
The perioperative management strategy is summarized in Table 9.8.


Weaning from CPB with VAD support
In order to wean from CPB, the heart is filled to a CVP of 8“10 mmHg. Once TOE confirms
that the left-sided cardiac chambers are sufficiently filled, the LVAD is initiated at the lowest
possible setting. As the LVAD flow rate increases, CPB is gradually reduced, taking care not
to overdistend the right ventricle. It is sometimes necessary to supplement the LVAD output
with CPB flows of 1“2 l/minute for the first 20“30 minutes before complete weaning. TOE is
used to confirm satisfactory LVAD cannula position and left heart decompression. TOE is
particularly useful in determining the adequacy of LV filling and monitoring the response of
the RV as CPB support is weaned; collapse of the LV wall around the LVAD cannula, or septal
distortion, are readily observed by TOE and indicate that the balance between the set LVAD
flow rate and cardiac filling needs to be addressed and that RV function may need to be further
optimized.
If LVAD flows of 2.2 l/minute/m2 cannot be achieved with CVP <15 mmHg, adequacy
of tissue perfusion should be assessed with mixed venous oxygen saturation measurement
(SvO2). Not infrequently, patients suffering from chronic heart failure are already accustomed
to a low cardiac output state and a cardiac index of 1.8 l/minute/m2 may be quite acceptable
provided that the SvO2 is satisfactory (> preimplant SvO2). Otherwise additional measures to
augment LVAD flows have to be considered.
As mentioned earlier, the output of an LVAD is dependent upon adequate right ventricular
function to deliver enough blood flow across the lungs to the left-sided cardiac chambers and
LVAD inflow. If LVAD flows are inadequate and the left heart appears empty on TOE despite
a full right heart, this is either due to right ventricular failure, elevated pulmonary artery
resistance or a combination of both. These can either be treated with low-dose infusions of
adrenaline and a phosphodiesterase inhibitor or with inhaled iloprost, respectively. However,
unless LVAD flows improve readily, CPB should be reinstituted early to avoid development of
metabolic acidosis. Under these circumstances, the early addition of a RVAD is advisable to
provide bi-ventricular support.


Postoperative management of VAD patients
At the end of the VAD implant, careful hemostasis is crucial in order to minimize hemorrhage.
An effective closed drainage system is essential in preventing mediastinal and pump pocket
collections. Some surgeons close the pericardial sac or place a surgical membrane between
the sternum and the mediastinum to facilitate subsequent re-sternotomy and re-entry. The
percutaneous cannulae or driveline must be secured externally in order to minimize move-
ment and trauma to the exit site(s). This is the best way to encourage tissue healing onto the
driveline and minimize exit site infections.
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Chapter 9: Mechanical circulatory support



Once returned to the intensive care unit, VAD patients must be closely monitored for early
complications (see Table 9.9). Antibiotic prophylaxis is continued for 48 hours. Coagulation
defects should be corrected without waiting for signs of bleeding. Right ventricular (RV)
function often remains precarious in the first few days following LVAD implantation. RV
failure can be precipitated by excessive LVAD flow rate and/or elevated pulmonary vascular
resistance (PVR). Therefore, it is prudent to limit the LVAD flow rate in the first few days in
order to avoid overwhelming the RV or shifting the ventricular septum to the left and distort-
ing RV dynamics. Furthermore, it is essential to avoid factors that may precipitate increases
in PVR, e.g., hypoxia and acidosis.
Anticoagulation is usually omitted in the first 24 hours and is only introduced when the
patient has stopped bleeding (<30 ml/hour for 3 consecutive hours). Most institutions com-
mence with an infusion of unfractionated heparin and this is continued for 5“7 days before
warfarin is commenced. The actual anticoagulation/antiplatelet regimen is device specific
and also unit specific.
Rising right atrial pressure coupled with a fall in pump flow rate are signs of tamponade
or impending RV failure. The latter can be confirmed with TOE, which demonstrates full
right-sided cardiac chambers with empty left-sided chambers. The atrial and ventricular septa
are seen to bulge towards the left and these are often accompanied by tricuspid valve regur-
gitation. Under these circumstances, it is important not to increase the preload further with
fluid transfusions. Immediate treatment consists of a combination of inotropic support for
the RV and pulmonary vasodilators. These may include adrenaline (up to 0.1 μg/kg/minute),
enoximone (5 μg/kg/minute), nitric oxide (up to 20 parts per million) and/or nebulized ilo-
prost (9.9 μg 3 hourly). If the situation does not respond readily to these measures, early con-
sideration should be given to the addition of an RVAD.

Long-term care
Long-term support of a VAD patient relies on a multidisciplinary approach. Dieticians are
involved from the preoperative period to ensure that nutrition is optimized. Most patients
would have been immobile for a long period of time and will require intensive physiotherapy
to facilitate their physical rehabilitation postoperatively. Anticoagulation therapy has to be
closely monitored to reduce the risk of thromboembolic and hemorrhagic complications. The
patient will need to be taught how to care for their driveline exit site to minimize the risk of


Table 9.9. Common complications of VAD support

Perioperative hemorrhage
Right ventricular failure
Cerebral vascular events
· Metabolic
· Embolic
· Hemorrhagic
Infection
Hemolysis
Thromboembolism
Mechanical pump failure

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Chapter 9: Mechanical circulatory support



infection. The patient will also need to be trained in all aspects of operating and maintaining
their VAD system, allowing them the freedom and independence to leave the hospital and
return to a normal life.

device for end-stage heart failure. New Engl
Suggested Further Reading J Med 2001; 345(20): 1435“43 (rematch
• Frazier OH, Kirklin J Mechanical trial).
Circulatory Support. ISHLT Monograph
• Samuels L, Narula J. Ventricular assist
Series. New York: Elsevier; 2006.
devices and the artificial heart. Cardiol Clin
• Goldstein D, Oz MC. Cardiac Assist Devices. 2003; 21(1).
London: Blackwell Publishing Ltd; 2002.
• Tsui S, Parameshwar J. Mechanical
• Rose E, Gelijns AC, Moskowitz AJ, et al. circulatory support. Core Topics
Long-term use of a left ventricular assist Cardiothorac Critl Care 2008: 157“66.




124
Deep hypothermic
Chapter

circulatory arrest
10 Joe Arrowsmith and Charles W. Hogue




The majority of cardiac surgical procedures are accomplished using cardioplegia-induced
cardiac arrest with cardiopulmonary bypass (CPB) to maintain perfusion to other organs.
However, in certain situations, the nature of the surgical procedure or the pathology of the
underlying condition necessitates complete cessation of blood flow. For example, safe removal
of large tumors encroaching on vascular structures requires provision of a bloodless field to
enable dissection, or operations on the aorta itself may preclude application of a cross-clamp
because of the pathological anatomy. Preservation of organ function during the period of
total circulatory arrest can be aided by reducing the core temperature of the body. The tech-
nique of core cooling combined with cessation of blood flow is termed “deep hypothermic
circulatory arrest” (DHCA).
DHCA provides excellent operating conditions “ albeit of limited duration “ whilst amel-
iorating the major adverse consequences of organ ischemia. During DHCA the brain is the
organ most vulnerable to injury, but may be protected if cooled to reduce its metabolic activ-
ity, and hence oxygen requirements, before and during the period of arrest. Similarly, pres-
ervation of the function of other organs less susceptible to ischemic damage may be afforded
by core cooling. DHCA owes its existence to two overlapping eras; a brief period in the early
1950s when hypothermia was used as the sole method for organ protection during surgery
and the current epoch of CPB heralded by Gibbon in 1953. Subsequent modifications to the
basic technique have extended both the duration of “safe” circulatory arrest and the range of
surgical indications.

Historical roots
In pioneering work during the 1940s and early 1950s, Bigelow demonstrated that a reduc-
tion in body temperature to 30°C increased the period of “safe” cerebral ischemia from 3 to
10 minutes “ time enough for expeditious intracardiac surgery. Hypothermic inflow occlu-
sion in cardiac surgery was first successfully achieved using cold rubber blankets for surface
cooling. The use of an iced water bath for cooling proved more practical and was adopted by
others with considerable success, notably in London by Holmes Sellors. The types of pro-
cedures that could be undertaken during inflow occlusion, however, were limited to atrial
septal defect repair, valvotomy and valvectomy. More profound degrees of hypothermia were
later described. Despite spectacular successes, the incidence of death and complications such
as hypothermia-induced ventricular fibrillation, hemorrhage, myocardial failure and neuro-
logical injury were high by today™s standards.
Although CPB-induced hypothermia and DHCA in the management of aortic arch
pathology had been described in the 1960s, it was Griepp, in 1975, who demonstrated that the
technique offered a relatively simple and safe approach for aortic arch surgery. DHCA, either
alone or in combination with other strategies, has remained the mainstay of brain protection
125
Cardiopulmonary Bypass, ed. S. Ghosh, F. Falter and D. J. Cook. Published by Cambridge University Press.
© Cambridge University Press 2009.
Chapter 10: Deep hypothermic circulatory arrest



Table 10.1. Applications of deep hypothermic circulatory arrest

Cardiothoracic surgery Thoracic aortic surgery
Pulmonary (thrombo) endarterectomy
Complex pediatric reconstructions
Neurosurgery Basilar artery aneurysm surgery
Cerebral tumor resection
Intracranial arterio-venous malformation resection
Other Caval mass resection (e.g., renal cell carcinoma)



during aortic surgery. In addition to being used to facilitate pulmonary vascular surgery and
the repair of congenital cardiac lesions, DHCA may also be used in both neurosurgery and
urological surgery (see Table 10.1).

Pathophysiology of hypothermia
In animals that maintain body temperature in a tight range, homeotherms, thermoregula-
tion occurs as a result of the dynamic balance between heat production (thermogenesis) and
heat loss. Stimulation of cutaneous cold receptors and temperature-sensitive neurons in the
hypothalamus activate vasoconstrictive, endocrine, adaptive behavioral and shivering mech-
anisms to maintain core temperature. Hypothermia, defined as a core temperature <35°C,
occurs when heat losses overwhelm thermoregulatory mechanisms (e.g., during cold immer-
sion) or when thermoregulation is impaired by pathological conditions (e.g., stroke, trauma,
endocrinopathy, sepsis, autonomic neuropathy, uremia) or drugs (e.g., anesthetic agents, bar-
biturates, benzodiazepines, phenothiazines, ethanol). Thanks to the early work of Rosomoff
and Currie (Rosomoff 1956), and experience gained from managing accidental hypothermia,
the physiological effects of hypothermia are well known (see Table 10.2). An understanding
of both normal physiological and pathological responses is essential when using deliberate or
therapeutic hypothermia.

Practical considerations
Preoperative assessment is similar to that for any other major cardiac surgical procedure.
Because DHCA is commonly used in emergent, life-saving procedures it may not be pos-
sible to undertake the usual battery of “routine” preoperative investigations. The presence of
significant comorbidities (e.g., coronary artery disease, cerebrovascular disease, renal insuffi-
ciency, diabetes mellitus) should be anticipated on the basis of the clinical history and physical
examination.

Anesthesia
Standard arterial, central venous and peripheral venous access is required in all cases. In
anticipation of division of the innominate vein to improve surgical access, venous can-
nulae should be sited in the right arm or in the femoral vein. Cannulation of the right
radial artery and a femoral artery permits arterial pressure monitoring both proximal
and distal to the aortic arch. Cannulation of a femoral artery also serves as an anatomical
marker for the surgeon should an intra-aortic balloon pump be required on separation
from CPB. Whilst not considered mandatory, pulmonary artery catheterization may aid
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Chapter 10: Deep hypothermic circulatory arrest



Table 10.2. The pathophysiology of hypothermia

Mild Moderate Severe
33“35°C 28“33°C <28°C
Neurological Confusion Depressed consciousness Pupillary dilatation
Amnesia Coma
Apathy Loss of autoregulation
Impaired judgment
Neuromuscular Shivering Muscle and joint stiffening Muscle rigor
Ataxia
Dysarthria
Cardiovascular Tachycardia Bradycardia Severe bradycardia Asystole
Vasoconstriction Increased SVR Ventricular fibrillation
Increased BP, CO Decreased cardiac output
ECG changes:
“ J (Osborn) waves
“ QRS broadening
“ ST elevation/depression
“ T wave inversion
“ AV block
“ QT prolongation
Respiratory Tachypnea Bradypnea Lactic acidosis
Left-shift HbO2 curve Bronchospasm Right-shift HbO2 curve
Bronchorrhea
Renal/metabolic Antidiuretic hormone Reduced glomerular filtration rate Metabolic acidosis
resistance
Reduced H+ and glucose
Cold-induced diuresis
reabsorption
Hematology Increased blood viscosity and hemoconcentration (2% increase in hemacrit/°C)
Coagulopathy “ inhibition of intrinsic/extrinsic pathway enzymes, platelet activation,
thrombocytopenia (liver sequestration)
Leukocyte depletion, impaired neutrophil function and bacterial phagocytosis
Gastrointestinal Reduced motility Ileus
Acute pancreatitis Gastric ulcers
Hepatic dysfunction




management immediately post-CPB and in the early postoperative period. Where avail-
able, and in the absence of contraindications, transesophageal echocardiography (TOE)
may be used to assess aortic valvular function, monitor cardiac function and assist with
cardiac de-airing.
Accurate temperature monitoring “ at two or more sites “ is crucial. Nasopharyn-
geal or tympanic membrane temperature monitoring provides an indication of brain
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Chapter 10: Deep hypothermic circulatory arrest



temperature, whereas rectal or bladder temperature monitoring provides an indication
of body core temperature. Whilst these devices are accurate at steady-state it should be
borne in mind that, during both cooling and warming, thermal gradients may be gener-
ated in tissues and monitored temperature may lag behind actual tissue temperature by
2“5°C.
The choice of anesthetic drugs is largely a matter of personal and institutional preference.
In theory, using propofol and opioid-based anesthesia in preference to volatile anesthetic
agents, reduces cerebral metabolism without uncoupling flow“metabolism relationships. The
impact of hypothermia on drug metabolism and elimination should be considered and drug
infusion rates adjusted accordingly.
The long duration of surgery with DHCA mandates careful attention to prevent pressure
sores and inadvertent damage to the eyes, nerve plexuses, peripheral nerves and pressure
points. Cannulation sites, three-way taps, monitoring lines, the endotracheal tube connector
and TOE probe should be padded to prevent pressure necrosis of the skin.
All measures should be taken to facilitate re-warming and prevent “after-drop” hypother-
mia following the termination of CPB. The use of a heated mattress, sterile forced-air blanket
and intravenous fluid warmer should be considered in all cases.

Surgical considerations
In some cases, such as acute type A aortic dissection, femoral or right axillary arterial can-
nulation may initially be necessary together with femoral venous cannulation to establish
CPB. Femoro-femoral or axillo-femoral CPB permits systemic cooling prior to sternotomy
and affords a degree of organ protection should chest-opening be accompanied by inadvert-
ent damage to the aorta, or heart, and exsanguination. After completion of the aortic repair,
placement of the arterial line directly into the prosthetic graft restores antegrade flow.
Cannulation of the mid or distal aortic arch may be required in cases of degenerative aortic
aneurysm to reduce the risk of atheroembolism associated with retrograde flow via femoral
arterial cannulation.
The choice of venous drainage site and cannula is largely dictated by surgical preference
and the degree of access necessary. For example, bicaval cannulation is required if retrograde
cerebral perfusion (RCP) is to be used with reversal of blood flow in the superior vena cava.
If antegrade cerebral perfusion is to be used with selective arterial cannulation of the carotid
arterial circulation then adequate cerebral venous drainage must be ensured, again using
bicaval cannulation, to optimize cerebral perfusion pressure and prevent cerebral edema.
Alternatively, selective antegrade cerebral perfusion may be obtained by arterial inflow into
the right subclavian artery. This potentially allows near continuous low flow to at least the
right cerebral hemisphere by the brachiocephalic artery. This technique simplifies the surgi-
cal field by elimination of carotid cannulation for antegrade perfusion and may reduce risk of
embolism or vessel injury. Removal of a renal tumor from the inferior vena cava requires the
use of a right atrial basket “ in preference to a caval or two-stage cannula “ to permit full visu-
alization of the cava and to prevent dislodged fragments of tumor from becoming impacted
in the pulmonary circulation.
The use of DHCA during surgery of the distal aorta via left thoractomy presents several
problems. Access to the proximal aorta is limited and femoral arterial cannulation may be
required initially. Access to the right atrium typically requires an extensive thoracotomy
that traverses the sternum. Alternatively, venous drainage may be achieved using pulmo-
nary artery cannulation or a long femoral cannula advanced into the right atrium.
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Chapter 10: Deep hypothermic circulatory arrest




Extracorporeal circulation
The nature of DHCA sometimes requires modifications to be made to the standard extracor-
poreal circuit including:
• infusion bags for the storage of heparinized blood during hemodilution (see below);
• use of a centrifugal pump “ in preference to a roller pump “ which may reduce damage
to the cellular components of the circulation and reduce hemolysis;
• incorporation of a hemofilter to control acidosis and hyperkalemia and enable hemo-
concentration during re-warming;
• incorporation of a leukocyte-depleting arterial line filter (see below);
• selection of a cardiotomy reservoir of sufficient capacity to accommodate the circulat-
ing volume during exsanguination immediately before DHCA;
• arterio-venous bypass and accessory arterial lines “ to permit retrograde or selective
antegrade cerebral perfusion (see below);
• an efficient heat exchanger. Assuming that human tissue has an average specific heat
capacity of 3.5 kJ/kg/°C (0.83 kcal/kg/°C), the energy required to warm a 70 kg adult
from 20°C to 37°C is at least 4.2 MJ (1000 kcal) “ the equivalent of the energy required
to raise the temperature of 12.5 l water from 20°C to 100°C; and
• the use of heparin-bonded circuits is advocated in cases requiring prolonged CPB,
although there is no conclusive evidence of benefit.


Cooling
Following anticoagulation, CPB is instituted with a constant flow rate of 2.4 l/minute/m2 and
cooling immediately commenced with a water bath to a blood temperature gradient of <10°C.
Vasoconstrictors (e.g., phenylephrine, metaraminol) or vasodilators (e.g., glyceryl trinitrate,
nitroprusside) are used to ensure a mean arterial pressure of 50“60 mmHg. As much of the
planned procedure as possible is carried out during the cooling phase prior to DHCA, in order
to minimize the duration of circulatory arrest.
Cooling continues until brain (e.g., nasopharyngeal) and core body (e.g., bladder) tem-
peratures have equilibrated at the target temperature for 10“15 minutes. In some centers,
continuous monitoring of the EEG, evoked potentials or jugular venous saturation is used as
a guide to the adequacy of cerebral cooling.

Circulatory arrest
As stated earlier, every effort should be made to reduce the period of ischemia. For this rea-
son preparation of any prosthetic grafts and as much surgical dissection as possible should
be undertaken during the period of cooling. The operating table is then placed in a slightly
head-down (Trendelenberg) position, the pump stopped, intravenous infusions stopped and
the patient partially exsanguinated into the venous reservoir. Once isolated from the patient,
blood within the extracorporeal circuit is recirculated via a connection between the arterial
and venous lines in order to prevent stagnation and clotting. The surgical repair proceeds with
heed to the duration of circulatory arrest.

Safe duration of DHCA
Determining the duration of DHCA that any particular patient will tolerate without sustain-
ing disabling neurological injury remains, at best, an inexact science. Current practice makes
129
Chapter 10: Deep hypothermic circulatory arrest




Figure 10.1 The effect of brain temperature on reported safe duration of deep hypothermic circulatory arrest
duration.



it difficult to separate the neurological risks of prolonged CPB, reperfusion and re-warming “ all
unavoidable consequences of DHCA “ from those of DHCA alone. The incidence of neuro-
logical injury rises sharply when DHCA exceeds 40 minutes. On the basis of animal experi-
mentation and clinical observation, DHCA, without additional neuroprotective measures is
typically limited to no more than 60 minutes at 18°C (see Figure 10.1). Frustratingly, while
some patients appear to tolerate DHCA >60 minutes without apparent injury, others sustain
major brain injury after <20 minutes DHCA.

Re-warming
Re-warming should be instituted following a planned rate of rise of core temperature. Exces-
sively rapid re-warming, accompanied by a rise in cerebral arterio-venous O2 difference,
is known to worsen neurological outcome. In patients undergoing coronary artery bypass
surgery, maintaining a temperature gradient of <2°C between inflow temperature and brain
(nasopharyngeal) temperature has been shown to improve cognitive outcome. Because hyper-
thermia is known to exacerbate neuronal injury, inflow temperature should not exceed 37°C
and CPB terminated when core body temperature reaches 35.5“36.5°C. A significant “after-
drop” is inevitable and patients are commonly admitted to the critical care unit with tempera-
tures as low as 32°C. Using a slow rate of re-warming with adequate time for even distribution
of heat between core and peripheral tissues helps to reduce the extent of this after-drop.
During the period of re-warming attention should be given to the correction of metabolic
abnormalities, particularly the metabolic acidosis that inevitably accompanies reperfusion
following circulatory arrest. Correction of acid“base balance may require the titrated admin-
istration of sodium bicarbonate or use of hemofiltration (ultrafiltration).
130
Chapter 10: Deep hypothermic circulatory arrest




Hemostasis
Prolonged CPB and hypothermia produce coagulopathy. Hemostasis is facilitated by metic-
ulous surgery, the use of predonated autologous blood and administration of donor blood
components under the guidance of laboratory tests of coagulation and thromboelastography.
Despite safety concerns, antifibrinolytic agents (e.g., tranexamic acid, µ aminocaproic acid)
and aprotinin have been shown to be efficacious in aortic arch surgery with DHCA. Recently
published and widely publicized studies reporting a high incidence of adverse effects associ-
ated with aprotinin use in adult patients undergoing coronary revascularization and high-
risk cardiac surgery have prompted withdrawal of the drug.


Neuroprotection during DHCA
Although hypothermia is the principal neuroprotectant during DHCA, additional strategies
may be employed to reduce the likelihood of neurological injury. These include: acid“base
management strategy, hemodilution, leukodepletion and glycemic control. Surgical maneu-
vers, such as intermittent cerebral perfusion, selective antegrade cerebral perfusion (SACP)
and retrograde cerebral perfusion (RCP), may also be used to both protect the brain and
extend the operating time available to the surgeon (see Table 10.3).


Hypothermia
Cerebral metabolism decreases by 6“7% for every 1°C fall in temperature below 37°C, with
consciousness and autoregulation being lost at 30°C and 25°C, respectively. At temperatures
<20°C, ischemic tolerance is around 10 times that at normothermia (see Figure 10.2). While
some authors maintain that the EEG becomes isoelectric at this temperature, it is evident
that a significant number of patients have measurable EEG activity at <18°C. In addition to
its effects on metabolic rate, hypothermia appears to reduce lipid peroxidation, neuronal cal-
cium entry, membrane depolarization, production of superoxide anions and the release of
excitotoxic amino acids.
In many centers, ice packs or an ice-cold water jacket placed around the head after induc-
tion of anesthesia are used to augment cerebral cooling. The extent to which extracranial


Table 10.3. Neuroprotectant strategies during DHCA

Anesthesia Glycemic control
External cranial cooling
Neurological monitoring
Cerebrospinal fluid drainage
Pharmacological neuroprotection
Perfusion Acid“base management strategy
Hemodilution
Leukocyte depletion
Surgical Intermittent cerebral perfusion
Selective antegrade cerebral perfusion (SACP)
Retrograde cerebral perfusion (RCP)

131
Chapter 10: Deep hypothermic circulatory arrest



120 35

CMR%
30
100 Safe CA

25
80
% Baseline




Minutes
20
60
15

40
10

20
5


0 0
37 32 30 28 25 20 18 15
Temperature (°C)
Figure 10.2 The effect of temperature on cerebral metabolic rate (CMR%) and duration of safe circulatory arrest
(CA). Data derived from McCullough et al. Ann Thorac Surg 1999; 67(6): 1895“9 and Kern et al. Ann Thorac Surg 1993;
56(6): 1366“72.



cooling influences brain temperature and neurological outcome in adult humans remains
undocumented. Use of the procedure is justified on the basis of an absence of significant
adverse effects and limited animal experimentation.

Hemodilution
The combination of vasoconstriction, increased plasma viscosity and reduced erythrocyte
plasticity secondary to hypothermia leads to impairment of the microcirculation and
ischemia. Progressive hemodilution during hypothermic CPB, typically to a hematocrit of
0.18“0.20, is thought to partially alleviate this phenomenon. In some centers, a degree of
normovolemic hemodilution is undertaken prior to the onset of CPB. The optimal hem-
atocrit for a particular individual at a specific temperature remains unclear. Gross anemia
(i.e., hematocrit <0.10) may result in inadequate oxygen delivery to tissues, particularly
during re-warming. This approach is supported by the more recent observation that main-
taining a higher hematocrit during deep hypothermic CPB did not impair the cerebral
microcirculation.

Acid“base management
Hypothermia increases the solubility of gases (e.g., N2, O2 and CO2) in blood. While the
total content of any particular gas in a blood sample remains constant, hypothermia shift s
the equilibrium between dissolved and undissolved gas leading to an increase in the
former, which in turn reduces the partial pressure of the gas. When analyzed at 37°C, a
“normal” blood sample taken during hypothermia reveals “normal” results, whereas cor-
rection of these results for body temperature reveals reduced PO2 and PCO2, and alkalosis.
Maintaining PCO2 within the normal range on the basis of analysis at 37°C is termed
132
Chapter 10: Deep hypothermic circulatory arrest



alpha-stat management, whereas maintaining a normal PCO2 (and pH) on the basis of
“temperature-corrected” analysis is termed pH-stat management. This is discussed further
in Chapter 6.
When cerebral perfusion pressure (CPP), PaO2 and PCO2 are maintained within the physi-
ological range, autoregulation couples cerebral blood flow (CBF) to cerebral metabolic rate
(CMRO2). Cerebral autoregulation is obtunded by profound hypothermia and hypercarbia. At
PaCO2>10 kPa the classical autoregulation “plateau” is abolished and CBF becomes “pressure-
passive” “ dictated solely by CPP. Alpha-stat management preserves cerebral autoregulation
and thus CBF decreases during hypothermia. By contrast, pH-stat management results in cer-
ebral hyperperfusion, which in turn increases O2 delivery and ensures more rapid and homo-
geneous brain cooling “ albeit at the potential expense of increased microembolic load.
In the piglet model of DHCA, pH-stat management improves neurological outcome. In
neonates undergoing DHCA for repair of congenital heart defects, pH-stat management
prior to circulatory arrest appears to be associated with fewer complications than alpha-stat
management and better developmental outcome. In adults, however, the superiority of one
strategy over another in the setting of DHCA remains unproven. Alpha-stat management is
used in many adult centers “ presumably on the basis of superior cognitive outcome following
hypothermic CPB, although some centers use a pH-stat strategy during cooling and an alpha-
stat strategy during re-warming.


Retrograde cerebral perfusion (RCP)
Reversing the direction of blood flow in the superior vena cava (SVC) has been advo-
cated as a means of improving brain protection during DHCA and extending the period of
“safe” DHCA. Following the onset of CPB, the cavae are snared and arterial blood directed
into the SVC via an arterio-venous shunt constructed in the CPB circuit. Pump flows of
150“700 ml/minute are advocated to maintain a mean perfusion pressure of ˜25 mmHg.
The putative advantages of RCP include continuous cerebral cooling, cerebral substrate
delivery and expulsion of air, particulates and toxic metabolites. The absence of blood flow
detectable by transcranial Doppler in the middle cerebral arteries of a small, but significant
number of patients subjected to RCP may explain conflicting evidence of efficacy. In addi-
tion, significant extracranial shunting via the external jugular veins may occur during RCP.
Interestingly, the use of multi-modal neurological monitoring to guide RCP delivery at
pressures as high as 40 mmHg “ considered by many surgeons to be harmful “ has shown
this to be safe.


Selective antegrade cerebral perfusion (SACP)
Selective hypothermic brain perfusion permits surgery to be conducted at lesser degrees
of systemic hypothermia (e.g., 22“25°C). SACP often requires greater mobilization of the
epiaortic vessels and division of the innominate vein. Following the onset of circulatory arrest,
the aortic arch is opened and balloon-tipped arterial cannulae advanced into the innominate
and left carotid artery ostia (see Figure 10.3). The left subclavian artery is clamped and arte-
rial flow commenced at 10“20 ml/kg to maintain a perfusion pressure “ measured in the right
radial artery “ of 50“70 mmHg. Alternative approaches include cannulation of the right sub-
clavian artery and hemicerebral perfusion via the innominate artery alone. The technique
provides more “physiological” cerebral perfusion, but has the disadvantage of increasing
operative time and carries the risk of atheroembolism and microembolism. In a recently pub-
133
Chapter 10: Deep hypothermic circulatory arrest




Figure 10.3 Examples of selective antegrade cerebral perfusion techniques. (a) Direct cannulation of the innomi-
nate and left carotid arteries. (b) Hemicranial perfusion via a left subclavian artery graft. (c) Bilateral cranial perfusion
via a left subclavian artery graft. (d) Bilateral cranial perfusion via a sidearm on vascular graft.


lished series of 501 consecutive patients undergoing aortic arch surgery with DHCA (25°C)
and SACP (14°C), Khaladj et al. reported an overall mortality of 11.6% and permanent neu-
rological deficit rate of 9.6%.
In some instances, intermittent, rather than continuous, antegrade cerebral perfusion is
considered more practicable or expeditious. In a piglet model of DHCA, 1 minute of reper-
fusion for every 15 minutes of DHCA has been found to be sufficient to provide normal meta-
bolic and microscopic cerebral recovery.

Leukocyte depletion
The use of leukocyte-depleting arterial line filters is reported to moderate the systemic inflam-
matory response to CPB, reduce reperfusion injury and reduce postoperative infective com-
plications. Evidence for cerebral protection by leukocyte depletion is lacking in humans and
animal experimentation has yielded conflicting results.

Glycemic control
Insulin resistance and hyperglycemia are common consequences of cardiac surgery and hypo-
thermia. In animal models, hyperglycemia worsens cerebral infarction. Whilst tight glycemic
control during cardiac surgery appears to reduce mortality and infective complications, any
neuroprotective effect remains unproven.
134
Chapter 10: Deep hypothermic circulatory arrest




Spinal cord protection
Surgery involving the descending thoracic aorta may interrupt blood flow to the spinal cord
via the anterior spinal artery (of Adamkiewicz) and cause paraplegia. Although drainage
of cerebrospinal fluid (CSF) has long been proposed as a means of improving spinal cord
perfusion, debate continues as to its efficacy. One early study suggested that postoperative
hypotension “ rather than avoidance of CSF drainage “ was the only predictor of paraplegia.
More recently, however, CSF drainage has been shown to reduce the incidence of paraplegia
or paraparesis by 80% in a randomized study of 145 patients undergoing thoracoabdominal
aortic aneurysm repair.
An alternative approach to spinal cord protection is the continuous infusion of ice-cold
saline into the epidural space. Despite reports of efficacy, the technique has not been widely
adopted.

Pharmacological neuroprotection
At present no drug is specifically licensed for neuroprotection during cardiac surgery. Over
the last four decades a wide variety of compounds, many with very promising preclini-
cal pharmacological profiles, have been evaluated in the setting of cardiac surgery. These
include anesthetic agents (barbiturates, propofol, volatile agents), calcium channel block-
ers, immunomodulators (corticosteroids, ciclosporin), amino acid receptor antagonists
(magnesium, remacemide), glutamate-release inhibitors (lignocaine, phenytoin), anti-
proteases (aprotinin, nafamostat) and free radical scavengers (mannitol, desferrioxamine,
allopurinol).
In many centers thiopental 15“30 mg/kg continues to be administered before DHCA despite
any objective evidence of efficacy. The widely held belief that thiopental reduces neurological
injury in conventional cardiac surgery is not borne out by the evidence, although there is some
suggestion that it reduces overall mortality. Animal evidence suggests that the administration
of corticosteroids (e.g., methylprednisolone 15 mg/kg) prior to DHCA affords a degree of neu-
roprotection. The recent demonstration of neuroprotection by sodium valproate in a canine
model of DHCA has prompted a randomized trial of valproate in humans.

Neurological monitoring
Until recently, the use of monitors of cerebral substrate delivery or neurological function
(see Table 10.4) has largely been confined to specialist centers, researchers and enthusiasts.
It goes without saying that a monitor must prompt a corrective intervention before the onset
of irreversible neurological injury to be of any use. Cost and lack of level 1A evidence of
efficacy means neurological monitoring has yet to be universally adopted as “standard of
care.”

Substrate delivery
Fiberoptic jugular venous oxygen saturation (SjO2) monitoring provides a continuous meas-
ure of the global balance between cerebral oxygen supply and demand. The normal range for
SjO2 is quoted to be 55“75%, but may be as high as 85% in some normal individuals. SjO2<50%
is regarded as being indicative of inadequate cerebral oxygenation. A normal or near-normal
SjO2 value may, however, mask regional cerebral ischemia; thus SjO2 monitoring has high
specificity but low sensitivity for the detection of cerebral ischemia. SjO2 monitoring has been
135
Chapter 10: Deep hypothermic circulatory arrest



Table 10.4. Neurological monitoring

Clinical Arterial pressure
Central venous pressure
CPB pump flow rate
Arterial oxygen saturation
Temperature
Hemoglobin concentration
Pupil size
Arterial PCO2
Substrate delivery Transcranial Doppler sonography
Near infrared spectroscopy
Jugular venous oxygen saturation
Cerebral activity Electroencephalography
Somatosensory evoked potentials
Auditory evoked potentials
Motor evoked potentials
Other Epiaortic ultrasound
Transesophageal echocardiography



used to assess the adequacy of cerebral cooling prior to DHCA. Low SjO2 prior to the onset of
DHCA is associated with adverse neurological outcome. SjO2 monitoring may also be used to
monitor the adequacy of SACP.
In contrast to measuring cerebral SaO2 and SjO2, which provide a measure of global cer-
ebral oxygen delivery and consumption, cerebral near infrared spectroscopy (NIRS) allows
measurement of a region of tissue containing arteries, capillaries and (predominantly) veins
(see Figure 10.4). Despite a lack of evidence of efficacy in adult cardiac surgery, NIRS is
widely used in DHCA to assess cerebral oxygenation during cooling, DHCA and re-warm-
ing. Under deep hypothermic temperatures it is unclear what “normal” values for SjO2 and
NIRS would be.
Transcranial Doppler (TCD) sonography has been mainly used as a surrogate measure of
CBF and a means for detecting microemboli. In the setting of DHCA it has been used to moni-
tor the adequacy of SACP, and assess autoregulation and CBF after surgery.

Neurological function
Qualitative and quantitative EEG has been used in cardiac surgery for over 5 decades and has
long been considered the “gold standard” for the detection of cerebral ischemia. Unfortunately,
a consistent and reproducible EEG descriptor of reversible cerebral injury has remained frus-
tratingly elusive. Although a sensitive indicator of neuronal injury, its use is complicated by
the fact that hypothermia and virtually every anesthetic drug have profound influences on
neuroelectrophysiology. Below 28°C there is progressive slowing until the EEG becomes iso-
electric “ a phenomenon used to assess the adequacy of cooling prior to DHCA. The tem-
perature at which EEG activity is lost is subject to considerable inter-patient variation and is
typically higher during the cooling phase than during re-warming.
136
Chapter 10: Deep hypothermic circulatory arrest




Figure 10.4 Near infrared spectroscopy monitoring during pulmonary thromboendarterectomy. Significant
cerebral desaturation is seen at the onset of CPB, during four periods of hypothermic circulatory arrest (DHCA), and
during re-warming.


Evoked potential monitoring encompasses a number of techniques that measure the
response of the nervous system to external stimulation. Sensory evoked potential moni-
toring techniques measure the cortical or brainstem responses to auditory, visual, spinal
cord or somatic stimulation. Motor evoked potential (MEP) monitoring techniques meas-
ure the spinal cord or compound muscle action potential response to cortical stimula-
tion. Abolition of specific components of the somatosensory evoked potential (SSEP) and
brainstem auditory evoked potential (BAEP) have been used as a measure of cooling prior
to DHCA.

Postoperative care
Postoperative care is similar to that for any patient undergoing cardiac surgery. Every effort
should be made to ameliorate the impact of secondary brain injury “ hyperthermia, hypox-
emia, hypotension and hypoperfusion should be aggressively treated. Even mild degrees of
hyperthermia, a common occurrence after cardiac surgery, have been shown to be detrimen-
tal after DHCA.

Outcome
The risks associated with DHCA are largely determined by the pathology being treated, the
presence of significant comorbidities and the urgency of surgery.
Surgery with DHCA carries a finite risk of neurological injury. The type and pattern of
neurological injury seen in neonates after DHCA appears to differ from that seen in older
children and adults. In neonates, the predominant lesion is neuronal apoptosis in the hippo-
campus and the gray matter of the cerebral cortex. Seizures and choreoathetosis are by far the
137
Chapter 10: Deep hypothermic circulatory arrest



most common clinical manifestations of neurological injury. By contrast, selective neuronal
necrosis and infarction (i.e., stroke) in the cerebellum, striatum and neocortex are the pre-
dominant lesions in non-neonates. In a study of 656 patients undergoing DHCA, Svensson
et al. reported an overall stroke rate of 7%. Univariate predictors of stroke included advanced
age, a history of cerebrovascular disease, DHCA duration, CPB duration and concurrent
descending thoracic aortic repair. In a study of 200 patients operated upon using DHCA
between 1985 and 1992, Ergin et al. reported an in-hospital mortality of 15% and stroke rate of
11%. Age >60 years, emergency surgery, new neurological symptoms at presentation and per-
manent postoperative neurological deficits were found to be significant predictors of opera-
tive mortality. Stroke was more common in older patients and when the aorta was found to
contain thrombus or atheroma. In 2008, a series of 347 DHCA patients from the Mayo Clinic
was reported (Sundt et al. 2008). That investigation detailed DHCA as well as introduction of
the protective adjuncts of retrograde or antegrade cerebral perfusion. For all patients mortality
was 9% and stroke was 8%. Following that report the preferred approach at the Mayo Clinic is
selective antegrade perfusion via the axillary artery, rather than retrograde cerebral perfusion.

• Furnary AP, Wu Y, Bookin SO. Effect of
Suggested Further Reading hyperglycemia and continuous intravenous
• Bigelow WG, Lindsay WK, Greenwood WF. insulin infusions on outcomes of cardiac
Hypothermia; its possible role in cardiac surgical procedures: the Portland Diabetic
surgery: an investigation of factors Project. Endocr Pract 2004; 10 (Suppl. 2):
governing survival in dogs at low body 21“33.
temperatures. Ann Surg 1950; 132(5):
• Griepp RB, Stinson EB, Hollingsworth JF,
549“66.
Buehler D. Prosthetic replacement of the
• Coselli JS, Lemaire SA, Koksoy C,
aortic arch. J Thorac Cardiovasc Surg 1975;
Schmittling ZC, Curling PE. Cerebrospinal
70(6): 1051“63.
fluid drainage reduces paraplegia after
• Hoffman GM. Neurologic monitoring on
thoracoabdominal aortic aneurysm repair:
cardiopulmonary bypass: what are we
results of a randomized clinical trial. J Vasc
obligated to do? Ann Thorac Surg 2006;
Surg 2002; 35(4): 631“9.
81(6): S2373“80.
• Doblar DD. Intraoperative transcranial
ultrasonic monitoring for cardiac and • Hogue CW Jr, Palin CA, Arrowsmith JE.
vascular surgery. Semin Cardiothorac Vasc Cardiopulmonary bypass management and
Anesth 2004; 8(2): 127“45. neurologic outcomes: an evidence-based
appraisal of current practices. Anesth Analg
• Dorotta I, Kimball-Jones P, Applegate R,
2006; 103(1): 21“37.
2nd. Deep hypothermia and circulatory
arrest in adults. Semin Cardiothorac Vasc • Khaladj N, Shrestha M, Meck S, et al.
Anesth 2007; 11(1): 66“76. Hypothermic circulatory arrest with
selective antegrade cerebral perfusion in
• Duebener LF, Sakamoto T, Hatsuoka S, et al.
ascending aortic and aortic arch surgery: a
Effects of hematocrit on cerebral
risk factor analysis for adverse outcome in
microcirculation and tissue oxygenation
501 patients. J Thorac Cardiovasc Surg 2008;
during deep hypothermic bypass.
135(4): 908“14.
Circulation 2001; 104(12 Suppl. 1):
I260“4. • Leyvi G, Bello R, Wasnick JD, Plestis K.
Assessment of cerebral oxygen balance
• Ergin MA, Galla JD, Lansman L, Quintana C,
during deep hypothermic circulatory arrest
Bodian C, Griepp RB. Hypothermic
by continuous jugular bulb venous
circulatory arrest in operations on the
saturation and near-infrared spectroscopy.
thoracic aorta: determinants of operative
J Cardiothorac Vasc Anesth 2006; 20(6):
mortality and neurologic outcome. J Thorac
Cardiovasc Surg 1994; 107(3): 788“97. 826“33.

138
Chapter 10: Deep hypothermic circulatory arrest



• Priestley MA, Golden JA, O™Hara IB, • Stier GR, Verde EW. The postoperative
McCann J, Kurth CD. Comparison of care of adult patients exposed to deep
neurologic outcome after deep hypothermic hypothermic circulatory arrest. Semin
circulatory arrest with alpha-stat and Cardiothorac Vasc Anesth 2007; 11(1):
pH-stat cardiopulmonary bypass in 77“85.
newborn pigs. J Thorac Cardiovasc Surg • Sundt TM 3rd, Orszulak TA, Cook DJ,
2001; 121(2): 336“43. Schaff HV. Improving results of open arch
• Rosomoff HL. The effects of hypothermia replacement. Ann Thorac Surg 2008; 86(3):
on the physiology of the nervous system. 787“96.
Surgery 1956; 40(1): 328“36. • Svensson LG, Crawford ES, Hess KR,
• Stecker MM, Cheung AT, Pochettino A, et al. Deep hypothermia with circulatory
et al. Deep hypothermic circulatory arrest: I. arrest. Determinants of stroke and
Effects of cooling on electroencephalogram early mortality in 656 patients.
and evoked potentials. Ann Thorac Surg J Thorac Cardiovasc Surg 1993; 106(1):
2001; 71(1): 14“21. 19“28.




139
Organ damage during
Chapter

cardiopulmonary bypass
11 Andrew Snell and Barbora Parizkova




Cardiac surgery may be associated with deterioration in the function of a number of organ
systems, commencing during surgery and persisting to varying degrees into the postopera-
tive period. Organ damage during cardiac surgery has been primarily attributed to the use
of cardiopulmonary bypass (CPB). Until recently it has been difficult to correctly distin-
guish the causative factors that are truly associated with CPB from those that result from
surgery. Although CPB continues to be the most widely used technique for the conduct of
cardiac surgical cases, there has been a resurgence of interest in the performance of coro-
nary artery bypass grafting without CPB, termed “off-pump CABG” or OPCAB for short.
The re-emergence of this technique has led to a number of studies evaluating organ func-
tion after cardiac surgery with and without the use of CPB and has resulted in an improve-
ment in the quality of the available information regarding the role of CPB in causing organ
dysfunction.

Triggers of organ damage
The key mechanisms in causing organ damage associated with CPB are:
• the activation of a systemic inflammatory response (SIRS), which is an inevitable
consequence of CPB;
• hemodilution and reduced blood viscosity, mainly at the onset of CPB, resulting in
alterations in the distribution of blood flow to organs and flow characteristics of blood
through capillary networks;
• ischemia/reperfusion injury to heart, lungs and organs supplied by the splanchnic
circulation;
• laminar rather than pulsatile flow, although the significance of this remains controversial.
The cause, nature and severity of organ dysfunction in the context of cardiac surgery and
CPB are described below in relation to each of the major organ systems. As cerebral and renal
dysfunction are perceived to be the most frequent and debilitating consequences of CPB, they
will be considered in separate chapters.

SIRS
The principal causative mechanisms of SIRS associated with cardiac surgery are:
• activation of complement;
• activation of fibrinolytic and kallikrein cascades;
• synthesis of cytokines;
• oxygen radical production; and
• activation of neutrophils with degranulation and release of protease enzymes.
140 Cardiopulmonary Bypass, ed. S. Ghosh, F. Falter and D. J. Cook. Published by Cambridge University Press.
© Cambridge University Press 2009.
Chapter 11: Organ damage in cardiopulmonary bypass



Transition from physiological circulation to CPB results in contact between blood and a
number of non-biological surfaces that form the extracorporeal circuit. This, together with
hypothermia, tissue trauma, organ ischemia and reperfusion and laminar flow, results in a
very complex response involving the activation of complement, platelets, macrophages,
neutrophils and monocytes. This massive, acute reaction initiates coagulation as well as the
fibrinolytic and kallikrein pathways. The resulting SIRS is amplified by the subsequent release
of endotoxins, cytokines, such as interleukins (IL) and tumor necrosis factor (TNF). Endothe-
lial cell permeability is increased. Release of proteases and elastases is triggered by the subse-
quent migration of activated leukocytes into tissue. The parenchymal damage caused by this
migration can exacerbate the ischemia/reperfusion injury associated with cardiac surgery
(Figure 11.1)
The evident features of SIRS are coagulopathy, vasodilatation, and varying degrees of
fluid shifts between the intravascular and the interstitial space, as well as the generation of



Cardiopulmonary
bypass




Endotoxins
Ischemia Complement
reperfusion activation
injury



Proinflammatory
cytokines




Cellular activation
(neutrophils,
endothelium, platelets,
leukocytes)




Toxic
metabolites




Tissue injury, Multiorgan dysfunction

Figure 11.1 Overview of the inflammatory response to CPB.

141
Chapter 11: Organ damage in cardiopulmonary bypass



microemboli. The clinical effect is mostly a temporary dysfunction, to varying degrees, of
nearly every organ system. However, SIRS can also be associated with major post-operative
morbidity such as neurological, pulmonary, cardiac or renal dysfunction. It still remains
unclear why two patients with similar physiological and perioperative variables may experi-
ence radically different degrees of this inflammatory response.

Contact activation
Contact between blood and the components of the CPB circuit, in particular the oxygenator
with its high surface area of synthetic material, and the direct exposure of blood to blood“gas
interfaces, for example, gaseous bubbles, results in the activation of three inter-related plasma
protease pathways:
• the complement pathway;
• the kinin“kallikrein pathway; and
• the fibrinolytic pathway.

Classical pathway:
Alternative pathway:
antigen“antibody complex
pathogen surface, cell
particles, antigens

C1
C3


Factor B C4



Factor D C2

C3 convertase


Histamine
C3 C3b + C3a release


+ C3 convertase


C5 convertase



Neutrophil
C5
C6 attraction and
C5b + C5a
C7
activation
C8
C9


Membrane attack
complex (MAC)
C5b6789

Figure 11.2 Overview of pathways activated following the exposure of patients™ blood to the CPB circuit.

142
Chapter 11: Organ damage in cardiopulmonary bypass



Factor XII +
anionic surface


Prekallikrein

Factor XIIa + XIIf
HMW
kininogen
C1 cleavage


Classical Factor XII
complement
pathway
Factor XI
Kallikrein

Facor XIIa
Coagulation
Factor XIa system
Bradykinin HMW kininogen

Fibrinolysis
Plasminogen Plasmin
Vasodilation


Pro-urokinase Urokinase tPA
Complement
pathway via C3
activation
Figure 11.3 Alternative and classical complement pathways are both activated during CPB. C3a and C5a, known
as anaphylaxotoxins, stimulate mast cell degranulation and act as a chemoattractant for neutrophils.



The complement system
The complement system consists of over 30 plasma proteins. Activation of complement causes
cellular injury either by the direct actions of activated complement components or as a result
of the activation of inflammatory cells by complement factors.
Activation of the system can occur through exposure to antigens, endotoxins or foreign
surfaces, through either a “classical” or “alternative” pathway (see Figure 11.2). Cleavage of
C3, by either route, to its activated form C3a stimulates the release of histamine and other
inflammatory mediators from mast cells, eosinophils and basophils. This results in smooth
muscle constriction and an increase in vascular permeability. C5a is a potent chemotactic
factor for neutrophils; C5a promotes the aggregation, adhesion and activation of neutrophils.
C3b and C5b interact on cell membranes with components C6“C9 to form a “membrane
attack complex,” which activates platelets and “punches” holes in cell membranes.
Plasma levels of activated complement factors rise within 2 minutes of the onset of bypass
and a second rise can be detected after release of the aortic cross-clamp and on re-warming.
Levels decline postoperatively and generally return to normal 18“48 hours postoperatively.

The kinin“kallikrein pathway
Contact with anionic surfaces results in the activation of factor XII to its activated forms, fac-
tors XIIa and XIIf. In combination with high-molecular-weight kininogen (HMWK), factor
143
Chapter 11: Organ damage in cardiopulmonary bypass



XIIa converts prekallikrein to kallikrein and, through a positive feedback loop, generates more
factor XIIa. Kallikrein cleaves HMWK bound to surfaces to yield bradykinin. Bradykinin
is a potent vasoactive substance that increases vascular permeability and promotes smooth
muscle contraction and secretion of tissue plasminogen activator (see below). Kallikrein and
factor XIIa cause neutrophil activation (see Figure 11.3).

The fibrinolytic pathway
Fibrin clots formed at an incision site are eventually broken down by plasmin. Bradykinin
promotes the production of tissue plasminogen activator (tPA), which converts plasminogen
to plasmin. Plasma activity of tPA increases to its maximum within 30 minutes of CPB and
usually returns to preoperative levels within 24 hours. In addition, kallikrein, in combination
with HMWK, cleaves pro-urokinase to urokinase. Urokinase activates urokinase plasmino-
gen activator (uPA), which causes more plasmin production. Plasmin proteolytically digests
fibrin to form fibrin degradation products (FDPs). Fibrin degradation products further
inhibit fibrin production and cause endothelial as well as platelet dysfunction.
Overall, thrombin formation and coagulation coincide with tPA release, plasmin forma-
tion and fibrinolysis. The effect is a state of global activation of thrombin formation, platelet
consumption paired with the activation of fibrinolytic pathways.


The role of the endothelium
Physiologically, endothelium plays a protective role by:
• secreting endogenous anticoagulants like tPA, thrombomodulin and heparin-like
substances; and
• producing relaxing factors like NO and prostacyclin.
Endothelial cells can become injured in the presence of circulating cytokines, endotoxins,
cholesterol, nicotine and sheer stress. Many cardiac patients will, therefore, have an activated
endothelium prior to surgery.
CPB causes further activation through the triggered release of inflammatory cytokines,
namely C5a, IL-1 and TNF. This will cause further expression of procoagulant and fibrinolytic
enzymes as well as expression of membrane adhesion molecules, which will allow the trans-
migration of neutrophils and monocytes.


Ischemia“reperfusion injury (IRI)
IRI is the term used to describe the cellular injury that occurs on resumption of normal per-
fusion to an organ after a period of relative or complete ischemia. During the ischemic period
intracellular calcium accumulates due to the failure of ATP-dependent cellular pumps. On
reperfusion, intracellular calcium levels further increase secondary to oxidative dysfunction
of sarcolemma membranes. This cellular and mitochondrial calcium overload ultimately
induces cardiomyocyte death by hypercontracture and opening of the mitochondrial perme-

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