CARDIOPLEGIA TYPES AND METHODS OF ADMINISTRATION

AUGUST 2017 FATHEENA

ABDULREHMAN MOHAMMED
CARDIOPLEGIA TYPES AND METHODS OF ADMINISTRATION
 August 2017 FATHEENA
ABDULREHMAN MOHAMMED

CARDIOPLEGIA TYPES AND METHOD OF ADMINISTRATION

Submitted to:

MANlPAL UNIVERSITY

A Project submitted in partial fulfillment for the award of

BACHELOR OF SCIENCE IN PERFUSION TECHNOLOGY

Degree to

MANIPAL UNIVERSITY

AUGUST 2017

By

Ms. FATHEENA ABDULREHMAN MOHAMMED

JUNE 2017
 Roll number - 141177001

SCHOOL OF ALLIED HEALTH SCIENCES,

MANIPAL UNIVERSITY, MANIPAL

CERTIFICATE

This is to certify that this project CARDIOPLEGIA METHODS AND TYPES

OF ADMINISTARTION is a bonafide work done by Ms. FATHEENA AB, Roll
number-141177001 in the Department of perfusion technology, School of Allied
Health Sciences, Manipal.

DEAN

DR. B. RAJASHEKHAR
School of Allied Health Sciences
Manipal University
Manipal- 576104
SIGNATURE: DATE:

JUNE 2017
SCHOOL OF ALLIED HEALTH SCIENCES,
MANIPAL UNIVERSITY, MANIPAL

CERTIFICATE

This is to certify that this project CARDIOPLEGIA TYPES AND METHOD

OF ADMINISTRATION is a bonafide work done by Ms. FATHEENA
ABDULREHMAN MOHAMMED, Roll number-141177024 under our
supervision and guidance. We are satisfied with the work presented by the
candidate towards the partial fulfillment of Bachelor of Science in Perfusion
Technology.

HEAD OF THE DEPARTMENT INCHARGE

Dr. S. GANESH KAMATH Mr. B. SHIVASHANKAR PAI

Professor and Head Assistant Professor and Co-ordinator
Department of Cardiovascular Department of Perfusion Technology
and Thoracic Surgery SOAHS, Manipal University
KMC, Manipal Manipal

SIGNATURE: SIGNATURE:
DATE: DATE:

DECLARATION

I hereby declare that this project titled CARDIOPLEGIA METHODS AND

TYPES OF ADMINISTATION has been carried out by me and this work has
not been submitted earlier to any other University for the award of degree or
diploma

Manipal FATHEENA

June 2017
 A Project submitted in partial fulfillment for the award of

BACHELOR OF SCIENCE IN PERFUSION TECHNOLOGY

Degree to

MANIPAL UNIVERSITY

August 2017

By

Ms. FATHEENA ABDULREHMAN MOHAMMED

EXTERNAL EXAMINER INTERNAL EXAMINER

SIGNATURE: SIGNATURE:

NAME: NAME:
DESIGNATION: DESIGNATION:

DATE: DATE

ACKNOWLEDGEMENT

I would like to take this opportunity to thank God for giving me the strength and courage through all
the days of my project. I would like to express my sincere gratitude to Dr. B. Rajashekhar Dean of School
of Allied Health Sciences for giving me the permission and opportunity to undertake this project. I would
like to express my sincere gratitude to Dr. Vasudev B. Pai Associate Professor and Consultant Cardiac
Surgeon, Dept. of Cardiovascular and Thoracic Surgery, KMC Manipal whose encouragement, guidance,
supervision and support helped me in successful completion of my work. I would also like to extend my
heartfelt thanks to Dr. S Ganesh Kamath Professor and Head, Dept. of Cardiovascular and Thoracic
Surgery, KMC Manipal who stood by us and provided us with all the help needed for completing my
project. My sincere thanks to Mr. B. Shivashankar Pai, Assistant Professor, Department of Perfusion
Technology, SOAHS Manipal University for his continual guidance, support and encouragement. My
sincere gratitude to Mr. Manu R Assistant Professor, Department of Perfusion Technology, SOAHS
Manipal University who guided me with his knowledge, expert comments, suggestions, support,
supervision, motivation and patience throughout my study. I would also heartedly like to thank Dr. Kapil
Minocha Asst. Professor, Dept. of Cardiovascular and Thoracic Surgery, KMC Manipal, Dr. Guruprasad Rai
D Sr. Resident, KMC manipal, Dr. Vljaya Kumar Cardiac Anesthesiologist, KMC Manipal Dr Rajkamal
Vishnu S K Sr. Registrar, KMC Manipal, Ms.Sonia Thomas Asst. Lecturer,Department of Perfusion
Technology, SOAHS Manipal University, Ms. Smrithi Asst. Lecturer, Department of Perfusion Technology,
SOAHS Manipal University and Mrs. Jiji Thampi Perfusionist, KMC Manipal for their continual support
and advice. I would like to thank all my friends for always lending a helping hand without any second
thought. Last but not the least my sincere thanks to those who directly and indirectly helped me in
successfully completing my Project.
 CONTENTS
INTRODUCTION

HISTORY

PHYSIOLOGY OF CARDIOPLEGIA

CARDIOPLEGIA TECHNIQUES

CARDIOPLEGIA CANNULAS

TYPES OF SOLUTION

CARDIOPLEGIA IN PEDIATRICS

CONCLUSION
ACCRONYMS
AI- Antegrade Injection

RI- Retrograde Injection

DI Direct Injection

IM Internal Mammary Artery

AMI- Acute Myocardial Infraction

CABG Coronary artery bypass grafting

CPK Creatinine phosphokinase

THAM Tris- hyroxymethyl aminomethane

HTK -Histidine-tryptophan-ketoglutarate
 INTRODUCTION

The word cardioplegia combines the Greek cardio meaning the "heart", and plegia
"paralysis". Technically, this means arresting or stopping the heart so that surgical
procedures can be done in a still and bloodless field. Most commonly, however, the
word cardioplegia refers to the solution used to bring about asystole of the heart, or
heart paralysis.

The main goals of hypothermic cardioplegia are:

Immediate and sustained electromechanical quiescence

Rapid and sustained homogenous myocardial cooling

Maintenance of therapeutic additives in effective concentrations

Periodic washout of metabolic inhibitors

The most common procedure for accomplishing asystole is infusing cold

cardioplegic solution into the coronary circulation. This process protects the
myocardium, or heart muscle, from damage during the period of ischemia.
To achieve this, the patient is first placed on cardiopulmonary bypass. This device,
otherwise known as the heart-lung machine, takes over the functions of gas
exchange by the lung and blood circulation by the heart. Subsequently, the heart is
isolated from the rest of the blood circulation by means of an occlusive cross-
clamp placed on the ascending aorta proximal to the innominate artery. During this
period of heart isolation, the heart is not receiving any blood flow, thus no oxygen
for metabolism. As the cardioplegia solution distributes to the entire myocardium,
the ECG will change and eventually asystole will ensue. Cardioplegia lowers the
metabolic rate of the heart muscle, thereby preventing cell death during the
ischemic period of time.

Myocardial protection during cardiac surgery is defined as the set of strategies

aiming at decreasing myocardial oxygen consumption adapting it to the
momentary tissue supply and/or at making cardiac cells more resistant to ischemic
episodes. The goal is to attenuate the magnitude of ischemia-reperfusion-induced
injuries and their noxious early and late consequences, such as acute myocardial
infarction (AMI), arrhythmias, ventricular dysfunction, cardiogenic shock and
increased perioperative mortality.

The importance of limiting ischemia-reperfusion injuries has been discussed for

more than three decades. Maroko et al., in 1971, have proposed that the extension
and severity of tissue injury alter coronary occlusion were not determined at
ischemia onset, but rather they could be changed by therapeutic manipulations
during ischemia. Since then, a large number of experimental studies have
investigated ischemic mechanisms and myocardial protection modalities. However,
few therapeutic interventions have shown to be clinically effective.

Among myocardial protection modalities used during cardiac surgeries, drugs and
anesthetic techniques improving tolerance to ischemia and contributing to protect
myocardial function are becoming increasing important for the clinical practice
and may influence better postoperative outcomes.
The objective of this review was to address injury mechanisms and myocardial
protection modalities with special emphasis to anesthetic techniques able to
promote heart protection.

Myocardial protection does not exist in isolation; non-cardiac organ protection for
the patient must be considered as well. Techniques that have been used to offset
myocardial protection have effects on the other organ systems and vice versa.

Additionally the development and evolution of myocardial protection have not

been linear ,most obviously demonstrated by the recent expansion of off-pump
techniques for coronary artery bypass grafting (CABG ).

This very term myocardial protection implies the potential for myocardial injury of
some type ,and in regard to cardiac surgery this is manifested as ischemia
reperfusion injury .The pathophysiology and underlying molecular biology of
myocardial injury are complex .Ischemia reperfusion injuries are can be broadly
grouped into two distinct categories ,reversible and irreversible .Reversible injury
is manifested by a transient depression in cardiac performance ,myocardial edema
and resolves without long term squeal. Irreversible cardiac injury involves
apoptosis or myocardial necrosis, and the results in electrocardiographic changes ,
release of myocardial specific enzymes such as creatinine phosphokinase (CPK) or
troponin into the circulation and lasting abnormalities of ventricular function
,either in hypokinetic or dyskinetic segments of the ventricle.

The term myocardial protection encompasses more than just cardioplegia and can
be said to include things such as the perioperative management of patients with
medical treatment (such as betablockers, etc.) or support devices (such as intra-
aortic balloon pumps), better anesthetic agents ,and better hemodynamic
management .All of these treatment contribute to making cardiac surgery safer ,and
to get a sick patient through a major operation .

Mechanism of myocardial protection with cardioplegia

Mechanical arrest (potassium induced ) will reduce oxygen consumption

Hypothermia will reduce consumption

 Aerobic metabolism can be maintained with oxygenated cardioplegia

Given just prior to the removal of the aortic cross clamp

Hot shot is delivered retrograde at 150-200ml/min at a temperature of 32-

37degreeC

Total dose of 30 ml/kg is ideally delivered over a 2-4 minute.

HISTORY

When developments in a scientific field are studied historically, it becomes

apparent that discoveries generally follow each other sequentially and for good
reason. Frequently a new development or contribution opens new vistas for further
study and uncovers hitherto unrealized problems that had not existed previously.
Discoveries are frequently made in response to a need, and the historic
development of techniques in myocardial preservation is no exception. For
example, there was no need to concentrate on preserving myocardium prior to
1953, the year that John Gibbon first successfully closed an atrial septal defect in
Philadelphia using cardiopulmonary bypass. The ensuing flurry, of activity
worldwide led to the rather rapid use of a variety of pumps and oxygenators as the
era of open heart surgery began. Surgeons soon learned that opening a chamber in
a beating heart rapidly led to lethal air embolism, which could be prevented
successfully only by stopping the heart. Another problem for the surgeon was poor
visibility in a blood-filled operative field, making this tedious operation even more
difficult. Both of these problems stimulated efforts to provide a quiet and dry field,
which could best be achieved by arresting the heart and temporarily stopping
circulation to the myocardium. The obvious way to achieve that objective was to
cross-clamp the aorta during the time required for the intracardiac repair. In their
zeal to master perfusion techniques and operative procedures, however, most
surgeons lost sight of the cause of significant perioperative mortality and were
generally unaware that inadequate intraoperative protection of the myocardium
during the procedure was a significant factor in a patient's demise. Before the
advent of pump oxygenators, some thoughtful investigators had begun to work
with various means of inducing hypothermia to protect the myocardium. Bigelow
and associates in Canada, Lewis and colleagues in Chicago, Swan and co-workers
in Denver, and Brock and Ross in London had already gained significant clinical
experience from 1950 to 1956, using total body hypothermia with transient
circulatory, interruption to perform cardiac operations. The concept of perfusion
hypothermia stimulated Brown and colleagues in Durham, NC, to develop a
practical heat exchanger with help from the Harrison Radiator Division of the
General Motors Corporation. Such heat exchangers allowed rapid cooling and
rewarming, and heat exchangers remain in use to this day. The profound
hypothermic techniques of Drew and Anderson in the United Kingdom also
emphasized the importance of cold in protecting the heart as well as the body as a
whole. Melrose and colleagues in England were among the first to realize the
potential value of arresting the heart and restarting it at will, that value being both
the prevention of air embolism and the production of a quiet operative field. Their
legendary animal experiments led them to standardize potassium citrate as a
method to achieve cardiac arrest. Unfortunately the high concentration of
potassium produced focal areas of necrosis in the myocardium, and this finding
served to slow progress in the use of cardiac arrest infusions for 10 years. Lam's
group in Detroit used acetylcholine for short-lived elective cardiac arrest, but its
effect proved to be too short to make it practical for regular use. In the mid-1950s,
Sealy , Young, and colleagues in Durham were working with various drugs to
prevent ventricular fibrillation. In the course of these studies, they developed a
solution containing potassium, magnesium, and neostigmine, and used the solution
for elective cardiac arrest along with hypothermia. Interestingly, they were the first
to use the term "cardioplegia" in the course of these studies. Doctor Sealy (personal
communication) recounts that they used this solution routinely until cardioplegia
went out of fashion in the 1960s. Being skeptical of potassium-containing solutions
because of increasing reports that they caused myocardial damage, Shumway's
group in California began using topical hypothermia with simultaneous aortic cross
clamping by circulating cold saline solution through the pericardial sac . This
lavage technique proved to be so successful that they have used it ever since. From
1966 to 1972, Denton Cooley and associates in Houston experimented with simply
cross-clamping the aorta at normothermic temperatures to produce arrest. To their
dismay, this caused ischemic contractures, and the term "stone heart" was coined.
In most of these cases of myocardial contracture, the patients had severe left
ventricular hypertrophy in the presence of far advanced aortic valve disease with
congestive failure. From 1961 until 1972, intensive studies were being carried out
in German cardiac centers by Holscher and associates Bretschneider and Kirsch
and colleagues who worked with various chemical additives to cardioplegic
solutions to provide safer cardiac arrest. The resulting multicomponent
cardioplegic solution, termed Bretschneider's solution, became the standard in
many centers. It is interesting that in 1970, while chemical cardioplegia and
noncardioplegic techniques were being tried, Benson Roe and associates in San
Francisco were infusing cold Ringer's solution containing 20 mEq of potassium to
cool the myocardium to 15C. They thought that this was a completely safe
cardioplegic mixture, and Dr Roe recounts that, at that time, it was becoming
universally accepted (personal communication). Although there were some centers
in which chemical cardioplegia was actively used, particularly in Europe, there was
little favorable use of this cardioprotective approach in the United States. However,
credit for a "second look" at potassium-induced cardioplegia in the United States
should go to Gay and Ebert . In 1973, they undertook a series of experiments
performed in New York with the initial idea that some type of chemical arresting
agent, in conjunction with hypothermia, would allow rapid and safe elective arrest.
This experiment resulted in a publication outlining functional, metabolic, and
morphologic effects of potassium-induced cardioplegia. It was a slow process to
attract surgeons back to potassium as a vehicle for achieving cardiac arrest,
particularly at a time when continuous coronary perfusion and the use of
ventricular fibrillation were popular. Gradually, however, the effectiveness and
safety of cold potassium cardioplegia were realized, and its use continues today.
Ebert has recalled their early experimental problems in dogs after 60 minutes of
normothermic cardioplegia , when the mortality rate was 40%. However, 6 months
later, the surviving animals were completely normal functionally, physiologically,
and pathologically, findings that made him quite skeptical of interpreting
physiologic and histologic studies acutely after cardioplegia. In 1976, Hearse and
colleagues described their development of an isolated rat heart perfusion
preparation that allowed them to evaluate a multitude of cardioplegic formulations.
Their studies using this preparation, calcium, glucose, and osmolality. It is
interesting that David Hearse had been introduced to Mark Braimbridge, a cardiac
surgeon at St. Thomas Hospital, by Sir Ernst Chain, and was invited to view their
open heart operations at St. Thomas (Hearse resulted in the development of the St.
Thomas solution , but what is more important, they contributed immensely to our
knowledge of physiology and chemistry of myocardial cells subjected to ischemia,
cardioplegic arrest, and subsequent reperfusion .Indeed, the basic tenets of surgical
myocardial protection had been established by this group, including the effects of
and optimal levels of hypothermia, potassium , ( personal communication). It was
Hearse's distress at the "medieval" way in which the myocardium had been
protected that set him to evaluating possible worthwhile cardioplegic formulations
with the aforementioned isolated rat heart preparation. Mr Braimbridge had been
using cold coronary perfusion with intermittent aortic clamping and was overjoyed
with Hearse's cardioplegic solution, remarking that although it might be of some
help to the coronary, arteries of his patients, it certainly was of immense help to his
own arteries! Hearse's continued productivity at the Rayne Institute of St. Thomas
Hospital is an excellent example of the scientific achievement that can result from
close cooperation between physiologists and surgeons. In 1978, Gerald Buckberg
and his group in Los Angeles reported reduced post ischemic myocardial damage
after modification of calcium, potassium, pH, and osmolality in a blood
cardioplegic mixture. Their monumental studies emphasizing the importance of
blood as a cardioplegic vehicle along with the addition of glutamate, aspartate, and
other additives for enrichment to energy-depleted myocardium represent major
milestones in myocardial preservation. More recently, these findings have been
applied to resuscitation of cardiogenic shock after acute myocardial infarction.
Along with Dr Vinten-Johansen, these investigators have evaluated different
modifications of blood cardioplegia, different administration techniques, and
control of the composition of blood cardioplegia with various additives to protect
the myocardium during long periods of arrest. Their achievements in identifying
surgical ischemic-reperfusion injury, and their attempts to prevent and treat
reperfusion injury based on the pathophysiologic mechanisms, are truly
noteworthy. In contrast to the aforementioned investigations, it is of interest that Dr
Akins, in Boston in 1984, had accumulated significant patient data using his
technique of hypothermic fibrillatory arrest without cardioplegia, with very low
mortality. His statistics are impressive and exemplify an alternative method of
myocardial protection. Solorzano and colleagues in Toronto gained the attention of
cardiac surgeons in 1978, when they induced the concept of retrograde coronary
sinus perfusion as an adjunct to myocardial protection. Even though Gott and
associates had described this technique in 1957, it had largely been unused until
this group reported their experience. Menasch6 and colleagues in Paris also
reported a large experience using retrograde coronary sinus perfusion and
emphasized its particular value in aortic valve operations. Advantages of the
retrograde route in facilitating the operative procedure as well as in protecting the
myocardium have attracted many cardiac surgeons, and the method has been in
widespread use for the past 10 years. Using this retrograde technique, Panos and
colleagues in Toronto began experimenting with warm continuous cardioplegia in
1989, and reported their results in 1990. Potential technical problems with the
technique, along with a lack of safe metabolic monitoring for the myocardium,
have slowed its adoption in many centers. Nevertheless, a flurry of research
activity continues, and this approach may well emerge as a preferred one in certain
clinical situations. It is apparent from this historical review that we owe a great
debt of gratitude to the aforementioned investigators and clinicians worldwide.
Their monumental contributions over the past 40 years have also demonstrated that
numerous methods of myocardial protection can be used successfully in given
situations. The controversies thus generated by different cardioplegic solutions,
vehicles, delivery modalities, and additives continued to stimulate further
investigation and clinical trials. Application of such findings should allow safer
operations and a higher recovery rate for patients around the world, and, it is
hoped, should spawn future generations of clinical as well as basic science
investigators as we continue to study and learn. For such we should be most
grateful!
 COMPONENTS OF CARDIOPLEGIA

The constitution of cardioplegia solutions varies according to individual surgeons

and institutional preferences. The composition of cardioplegic solutions has been
described as being similar to either the ionic composition of extracellular or of
intracellular fluid depending on the content of sodium, potassium, calcium and
magnesium of a given type of cardioplegia. Cardioplegia solutions can be further
categorized according to whether they are crystalloid or blood based. The essential
requirement for attainment of rapid diastolic cardiac arrest, however, renders
potassium (2040 mEq/l), which causes membrane depolarization, an essential
ingredient of all cardioplegia solutions.
Other components common to cardioplegia solutions include sodium (100200
mEq/l) and chloride ions. Sodium minimizes the transcellular sodium gradient and
so reduces intracellular edema; marked extracellular hyponatremia (<50 mEql),
together with excessive potassium-induced membrane depolarisation, alters the Na
+ /Ca 2+ exchange mechanisms in such a way as to promote intracellular Ca 2+
accumulation causing damage to sarcolemma membranes. Chloride ions maintain
the electroneutrality of the solution.
Modification of cardioplegia to produce a solution that provides optimal
preservation of myocardial function has led to a variety of additions to the basic
ingredients, for example one of the most established blood cardioplegia
preparations contains citrate phosphate dextrose CPD), to limit calcium infl ux
during ischemia, and tromethamine (tris-hydroxymethyl aminomethane, THAM), a
buff er that prevents acidosis. THAM diff uses into the intravascular space,
captures the CO2 produced by metabolic acidosis and improves myocardial
performance.
The original cardioplegic solutions used for many years consisted of crystalloid
solutions with various additives. The most widely used is the St. Thomas Hospital
solution. Calcium, in low concentration, is included in the solution to ensure that
there is no likelihood of calcium paradox during reperfusion and to maintain
integrity of cell membranes. Magnesium may help stabilize the myocardial
membrane by inhibiting a myosin phosphorylase, which protects ATP reserves for
post ischemic activity. The protective effects of magnesium and potassium have
been shown to be additive. Procaine, a local anesthetic, is included in low
concentration, to counteract the vasoconstrictive effects of particulate contaminants
in the infusion and so promote even distribution.
St. Thomas solution is usually buffered by the addition of sodium bicarbonate just
prior to use; this renders the solution slightly alkaline and helps compensate for the
metabolic acidosis that accompanies ischemia. Commercially prepared bags of
ready diluted St. Thomas cardioplegia are available as an alternative to diluting the
concentrate with Ringers, but differ slightly from the original St Thomas
preparation.
Hypothermic crystalloid cardioplegia has certain disadvantages, including the fact
that it inhibits the enzyme Na + /K + adenosine triphosphatase, which is intrinsic to
the function of transmembrane ion pumps, thereby producing myocardial edema
and consequent activation of platelets, leukocytes and complement.
Blood cardioplegia largely replaced crystalloid cardioplegia in most centers several
years ago. It consists of four parts of blood to one-part crystalloid cardioplegia
solution. The is limits the systemic hemodilution seen with crystalloid
cardioplegia during repeated infusions. Blood cardioplegia maintains oncotic
pressure, is a natural buffering agent, has advantageous rheological properties and
is a free radical scavenger. It also limits reperfusion injury in the acutely ischemic
myocardium. Experimental studies have shown that normal hearts subjected to up
to 4 hours of ischemia have complete recovery of function when intermittent cold
blood cardioplegia is infused. Cold blood cardioplegia alone, however, does not
totally avoid injury. The Krebs cycle amino acids glutamate and aspartate are
depleted during episodes of intermittent blood cardioplegia administration. Th ey
are especially depleted in chronically ischemic hearts and may be replenished by
using blood cardioplegia with added glutamate and aspartate, oft en referred to as
substrate-enhanced cardioplegia. Blood cardioplegia, with or without substrate
enhancement, may be infused as a warm solution to optimize the metabolic rate of
repair, just prior to removal of the aortic cross-clamp, at the end of the intended
ischemic period. The warm phase has been referred to as the hot shot of
cardioplegia . It enhances cellular assimilation of the substrates, augmenting the
rate of recovery of myocardial contractility. Some surgeons also infuse a small
volume of warm blood cardioplegia followed by cold cardioplegia to induce
cardiac arrest at the commencement of the ischemic period, on the basis that this
feeds the heart, i.e., provides a more physiological delivery of oxygen and
substrates for the period of ischemia
 CARDIOPLEGIA TECHNIQUES

To be effective the desire volume of cardioplegic solutions must be evenly

distributed throughout the myocardium. Obstacles to this goal include coronary
stenosis, which prevent uniform delivery of cardioplegia, often to the most
vulnerable regions of the myocardium, and aortic regurgitation. Aortic
regurgitation, even when mild, lowers aortic root pressure , so reducing the
perfusion pressure of cardioplegia infused into the aortic root ,and also causes loss
of cardioplegia into the left ventricle .Hence ,the time honored method of
antegrade aortic root infusion of cardioplegia alone can be combined with
retrograde cardioplegia infusion into the coronary sinus to overcome the
potential for inadequate myocardial preservation.

ANTIGRADE DELIVERY

Typically, a cannula for antegrade cardioplegia is placed high and slightly to the
right side of the ascending aorta, secured with a pursesuture, which is tied at the
end of the operation. The cannula may include a pressure line and a vent port to
suction air and blood between infusions. Antegrade infusion pressure during
delivery of cardioplegia must be monitored. High pressures (>80mmHg) may
cause endothelial damage and myocardial edema. Monitoring pressure in the
cardioplegia delivery system allows detection of inadvertent line occlusion by
clamping or kinking. However, using the delivery system line pressure alone to
estimate aortic or coronary sinus pressure is inaccurate. Accurate infusion pressure
is obtained through a line directly attached to the infusion port. Such systems are
widely available commercially.
Antigrade infusion pressure should be kept between 60 and 80 mmHg. High
pressure during is most likely to be due to extensive coronary stenotic lesions ;the
rate of infusion should be slowed to permit infusion of the required volume
(usually 300 ml/minute for 2 minutes ).If there is mild aortic insufficiency
,antegrade cardioplegia will be infused partially into the left ventricle and will not
distributed into the myocardium effectively . Light manual pressure applied to the
right ventricle will often help close the left ventricular outflow tract. The
perfusionist can confirm that cardioplegia is flowing through myocardium by
checking aortic pressure and observing myocardial temperature change.
Alternatively ,the aortic root can be partially opened and cardioplegia directly
infused into the coronary ostia using handheld or self-inflating balloon catheters.

Further antegrade infusions of cardioplegia may be administered during CABG via

the proximal ends of vein grafts on completion of each distal anastomosis

The limitations of antegrade cardioplegia without provision for its distribution

beyond coronary stenosis are well recognized .These limitations can be overcome
by delivering cardioplegia by direct graft perfusion (as described by the authors),
performing proximal grafting before aortic clamping and administering
cardioplegic infusions via the aorta after each distal graft, or performing sequential
distal and proximal anastomoses during aortic clamping and giving cardioplegia
via the aorta after each proximal and distal connection is complete. Each
aforementioned technique protects jeopardized myocardium when vein grafts are
employed. These strategies do not, however, ensure adequate distribution of
antegrade cardioplegia if there is diffuse coronary disease and all areas of
contracting myocardium cannot be revascularized, or if the internal mammary
artery graft is the desired conduit without risking damage to jeopardized muscle.
Long-term studies document the superior patency of internal mammary artery
(IMA) grafts, and our cardiologic colleagues desire their routine use, even during
the increasing number of emergency coronary operations performed currently in
critically ill patients.
 RETROGRADE DELIVERY

A cannula for retrograde administration of cardioplegia is inserted through the

lower part of the right atrium into the coronary sinus ,usually before
cardiopulmonary bypass is started .A cannula ,designed for the placement in the
coronary sinus ,with a malleable stylet and a self inflating ,or manually inflated
,balloon is commonly used .The retrograde cannula is is directed at a 45 degree
angle towards the left shoulder in the path of the coronary sinus and positioned
distally beneath the left atrial appendage .The cannula tip is palpated as it passes by
the junction of the inferior vena cava and right atrium into the coronary sinus .If
the cannula is directed into the posterior descending vein ,it should be withdrawn
slightly and reinserted .If difficulty is encountered during placement ,it is helpful
to commence CPB and lift the apex of the heart .The surgeon can then directly
view and palpate the tip of the cannula making it easier to insert .In re
operations ,if the posterior ventricular wall is adherent to the pericardium
,placement of the retrograde cannula may be attempted prior to the CPB ,but prove
difficult .Alternatively ,after CPB is instituted ,adhesions can be dissected away
from the heart and the cannula positioned more readily .

Failure to intubate the coronary sinus is rare (under 2%of cases) and indicates a
fenestrated thebesian valve or a flap over the coronary sinus ostium. When this
occurs , bicaval cannulation may be used ,permitting opening of the right atrium
and direct insertion of the retrograde cannula into ostium of the coronary sinus
.During infusion of retrograde cardioplegia ,the Perfusionist should monitor the
infusion pressure and reduce flow ,if needed ,so as not to exceed a pressure of
about 40mmHg.High pressure usually indicate that the catheter is advanced too far
and should be withdrawn slightly

The coronary sinus can be injured by forceful cannulation or continued infusion of

cardioplegia with coronary sinus pressures exceeding 40mmHg .perforation of the
sinus is manifest noting blood within pericardial well during cardioplegia infusions
.Perforation can be directly repaired with a 5-0 suture or with pericardial pledgets
if the tear site is not distinct .If a hematoma is noted ,retrograde infusions should be
discontinued .No further action is needed because low venous pressure allows self
containment after heparin reversal .

Coronary sinus pressure <20mmHg infers that the balloon is not inflated or not
occluding the coronary sinus. The catheter may have migrated out of the coronary
sinus into the right atrium .The cannula tip and balloon should then be palpated and
repositioned .Added maneuvers to improve retrograde infusion include finger
compression of the junction of the coronary sinus and the right atrium or placement
of a snared suture around the coronary sinus ,thus fixing it in place and preventing
regurgitation of cardioplegia into the atrium .A rare cause of low retrograde
infusion pressure is the presence of the left superior vena cava .This is usually
determined before cardiopulmonary bypass and the vessel occluded with a
tourniquet only if an intact innominate vein is present .If the innominate vein is
absent ,only antegrade cardioplegia is used .

DELIVERY THROUGH BYPASS GRAFT

Antegrade cardioplegia can be delivered through previously placed bypass grafts

and then utilized as an adjunct to both root delivered antegrade and retrograde
cardioplegia doses. Delivery of cardioplegia through bypass conduits offers several
advantages .Firstly ,cardioplegia is delivered to an area presumably underserved by
antegrade coronary flow .Secondly ,through bypass conduit is relatively
nonobtrusive and can therefore be delivered either intermediately or continuously
without disruption of the surgery .Finally ,if pressure and flow monitoring are
available ,the delivery rate at a given flow can give an indication regarding the
runoff and patency of the bypass graft.
 COMBINED ANTEGRADE AND RETROGRADE CARDIOPLEGIA

The use of combined retrograde and antegrade cardioplegia allows the surgeon to
capitalize on the advantages of each method and eliminate many of the
shortcomings present when only technique is used .Most frequently ,antegrade and
retrograde cardioplegia are delivered independently as the operative situation
dictates. However ,simultaneous delivery of both antegrade and retrograde
cardioplegia appears to be safe .Initial concerns speculated that combined delivery
of both antegrade and retrograde cardioplegia could result in high pressures within
the cardiac vasculature and subsequent edema ,hemorrhage ,and myocardial
injury .Infact ,the simultaneous delivery of antegrade and retrograde cardioplegia
provide more homogenous delivery of cardioplegia and superior myocardial
protection compared with other techniques .One technique of simultaneous
antegrade and retrograde delivery of retrograde cardioplegia involves the delivery
of retrograde cardioplegia while antegrade cardioplegia is delivered through a
completed bypass graft to the right side .The technique is designed to eliminate the
potential for under-perfusion of the right ventricle and septum that exist when only
retrograde cardioplegia is delivered .

CARDIOPLEGIA TEMPERATURE
Crystalloid cardioplegia solutions are usually delivered at 4C, cold blood solution
at 10 -16C and warm blood solutions at 37C.

Adequacy of cardioplegia distribution can be confirmed by monitoring myocardial

temperature .The temperature probe can be placed in the septum first, the most
vulnerable area, and then moved according to the surgeons preferences to other
regions of the heart .Temperature is generally kept below 15C .Sometimes more
cardioplegia needs to be infused to reach low temperatures , e.g. in the face of
severe left ventricular hypertrophy commonly seen in hypertensive patients or in
the setting of severe aortic stenosis .Inadequate cooling is sometimes seen if the
two staged venous cannula indirectly distorts the non-coronary cusp of the aortic
valve ,resulting in aortic regurgitation during cardioplegia infusion. Simply
repositioning the cannula in the field will correct this problem. Excessive blood
accumulating in the heart during cardioplegic arrest leads to inadvertent
myocardial re-warming and can be prevented by judicious use of vent suckers to
drain the ventricles.
 METHODS OF ADMINISTRATION

A) CONTINOUS CARDIOPLEGIA

The Heart is normally perfused in a continuous manner. Additionally, increases in

myocardial acidosis have been noted between cardioplegia doses .Continuous
cardioplegia was found to be superior in terms of postoperative left ventricular
stroke work index. Additionally, patients in the continuous cardioplegia group were
found to require less inotropic support and had lower levels of lactate and
hypoxanthine in coronary sinus effluent following aortic unclamping.

Advantages

Normal Perfusion

Increased post-operative left ventricular function

Decreased inotropic requirement

Disadvantages
 Wet operative field

Complexity

B) INTERMITTENT CARDIOPLEGIA

Lichtenstein and co-workers, who originally described the technique, admit to

temporarily interrupting the infusion of warm blood for periods of up to 15
minutes. Yau and colleagues have also used warm blood cardioplegia in a
multidose fashion. A problem with continuous infusions of cardioplegia is that the
operating field will be flooded with blood .One solution is to use retrograde
perfusion which increase visibility due to decreased coronary artery flow but the
perfusion of the right ventricle will be suboptimal. Continuous saline irrigations,
suction, or blower devices can be applied in the vicinity of the opened vessel to
improve visibility but despite this ,conditions will not optimal .

Advantages

Improved surgical procedure

Low cardioplegia volume

Disadvantages

Increase interdose myocardial acidosis

 CARDIOPLEGIA CANNULA

Retrograde Cardioplegia Cannula

retrograde cardioplegia cannulae are intended to be connected to the cardioplegia

line in order to infuse cardioplegic solution and blood into the patient's coronary
sinus during open heart procedure.

Specifications
- balloon diameter: 18mm
- length: 31cm
- 14Fr
Features & Benefits
- self-inflating
- silicone balloon
- malleable stylet

ANTEGRADE CANNULA

Antegrade cannulae are designed to deliver cardioplegia solution to the heart

via the coronary ostia in the normal direction of blood flow (antegrade
perfusion)

Features
 Suture flange

Luer locking
needle

CORONARY OSTIA CANNULA

Cardioplegia Coronary Ostium Cannulae from Sorin is used for the direct
cannulation of the coronary ostium to deliver cardioplegic solution.
Features:

Silicone ensures no sensitivity to cold and adaptation to anatomical

conditions

Additional openings ensure homogeneous perfusion of the cardioplegia

solution

Available with tip angle 90 or 135

Available with malleable stainless steel tube or flexible plastic tube

Available with 1/4" connector or female luer lock connector

Available sizes: 9, 11, 12, 14 and 15 French (3.0, 3.5, 4.0, 4.5 and 5.0 mm)

Length: 26 cm

AORTIC ROOT CANNULA

Antegrade delivery of cardioplegia solutions and venting of the heart

Andocor aortic root cannulae are intended for use during cardiopulmonary bypass
for antegrade delivery of cardioplegia solutions and venting of the heart. The
cannula may also be used to aspirate air from te aorta at the conclusion of the
cardiac procedure.

A needle secures a precise and quick insertion and a flange guarantees a

predetermined insertion depth and a safe point to secure the cannula.

Different configurations
- with or without vent line
- 6Fr, 7Fr, 9Fr
- length 15cm or 28cm
- 1 or 2 clamps

CARDIOPLEGIA ADAPTER
Cardioplegia adapters connect to the aortic root cannula or vessel cannulae and are
intended for the delivery of cardioplegia solution or venting the heart during
cardiopulmonary bypass.

A perfusion adapter with 2 male luer lock, 1 female luer lock and color-coded
clamps
- Multiple perfusion adapter for aortic root and three vein grafts
 MINIMIALLY INVASIVE CARDIAC SURGERY CANNULA

Provide optimal blood flow with the smallest possible size

Facilitate femoral and direct cannulation of vessels.
 CARDIOPLEGIC SOLUTION

Cardioplegic Solution is a sterile, nonpyrogenic, essentially isotonic, formulation

of electrolytes in Water for Injection, USP. It is a core solution intended for use
only after addition of sodium bicarbonate to adjust pH prior to administration.
After buffering with sodium bicarbonate, it is suitable for cardiac instillation
(usually with hypothermia) to induce arrest during open heart surgery. It is required
that 10 mL (840 mg) of 8.4% Sodium Bicarbonate Injection, USP(10mEq each of
sodium and bicarbonate) be added aseptically and thoroughly mixed with each
1000 mL of Cardioplegic solution to adjust pH. After this addition, the solution
must be stored under refrigeration and be used within 24 hours. The solution
contains no bacteriostat, or antimicrobial agent and is intended only for use (after
adjusting pH with sodium bicarbonate) in a single operative procedure. When
smaller amounts are required, the unused portion should be discarded.
Cardioplegic solution with added sodium bicarbonate used as a coronary artery
infusate induces cardiac arrest, combats ischemic ionic disturbances, buffers
ischemic acidosis and protects energy sources for functional recovery after
ischemia.
Available dosage form in the hospital: 20ML AMP

Common side effect: Intraoperative and perioperative potential hazards of open

heart surgery includes myocardial infarction, electrocardiographic abnormalities,
and arrhythmias, including ventricular fibrillation. Spontaneous recovery after
Cardioplegic cardiac arrest may be delayed or absent when circulation is
restored. Defibrillation by electric shock may be required to restore norm

TYPES OF SOLUTION
 CRYSTALLOID SOLUTION
BLOOD
MICROPLEGIA

Custodiol HTK Solution Multi Organ Transplantation

For many doctors, nurses, and the general public the term life support calls up the
image of a ventilator. However, there are many types of life support, one of them
being organ transplants. As with any other type of life support, organ
transplantation comes with its share of problems.

Forty years ago, many people died because doctors could not successfully
complete a transplant and prevent rejection of the new organ. The knowledge of
anti-rejection drugs was limited, and the surgery involved was extremely difficult.
Today, science has made improvement in the field of transplantation to the point
that most transplant operations are considered low risk. The success rate is high for
kidney transplants, liver transplants, cornea transplants, and even heart and lung
transplants.

The credit for high success rate of transplantation can be given to the new
technology which involves preserving the organs in the right manner.
Custodiol HTK Solution is used by leading Transplant Centers worldwide for the
preservation of the kidney, liver, heart, lung and pancreas during organ
transplantation.
In-situ protection: Due to high systemic tolerance all kinds of operation procedures
in ischemic organs may be perfomed such as heart surgery, kidney tumor resection
and split liver donation.
Transplantation
Multi organ procurement using Custodiol HTK solution
Reliable preservation of donor organs
Easier handling due to simultaneous in-situ perfusion of all organs
Increased organ availability due to excellent postoperative function,
even with kidney of non-heart beating donors

Autologous graft protection with Custodiol HTK solution

Excellent preservation of venous and arterial grafts
Reduced rise in permeability of the endothelial cell layer
Effective even at room temperature

Custodiol HTK solution for Cardiac surgery and Transplantation

High rate of spontaneous return to sinus rhythm
Minimized cell necrosis
Less depletion of ATP stores
Remarkably increased protective potency

Liver Transplantation with Custodiol HTK solution

Extended cold preservation time
Better preservation of micro-circulation
Low degree of cell edema
Prevention of leukocyte adhesion
Reduced biliary tract complications

Kidney Transplantation with Custodial HTK solution

Rapid graft function
Prolongation of ischemic tolerance
Lower frequency of post-operative dialysis
Shortened hospitalization
Good Structural protection even at 25 C
 High rate of long time graft survival

Heart Transplantation with Custodiol HTK solution

High rate of spontaneous return to sinus rhythm

2) Minimized cell necrosis
3) Less depletion of ATP stores
4) Remarkably increased protective potency

Lung Transplantation with Custodiol HTK solution

Good pulmonary tissue preservation in conjunction with prostaglandins,

Excellent postoperative functional result
Low post-transplant pulmonary edema
Good preservation of combined heart-lung graft

Pancreas Transplantation with Custodiol HTK solution

1) Good endocrine and exocrine function of pancreatic tissue post-

operatively
2) Suitable for in-situ flush of human pancreases prior to subsequent islet
isolation, culture and transplantation
3) Reliable graft function in a porcine model after upto 24 hours cold storage

Properties of Custodiol HTK solution

1) Low potassium concentration to minimize risks
2) Low sodium concentration for safe organ inactivation
3) Extended buffer capacity only possible with high histidine / histidine-Hcl
concentration
4) Tryptophane supports membrane integrity
5) Alpha- ketoglutarate serves as a substrate for aerobic energy production
during the induction of cardioplegia, and when restarting the heart
6) HTK is perfused as a cold solution, so that its hypothermic effect
contributes to a decreased metabolic rate
7) All components of HTK solution are naturally occurring physiological
substances except for the inert mannitol, therefore no toxic effects have ever
been observed

Advantages of Custodiol HTK solution

1) Use in-situ and during hypothermic storage

2) Rapid homogenous cooling due to low viscosity
3) Superior recovery of function
4) Excellent ischemic tolerance
5) High buffering capacity
6) Easier surgical handling due to excellent visibility
7) Reduced risk of post-aggression syndrome
8) Virtual absence of side effects
9) Simple perfusion technique (ready-to-use, no additives or preparation)
saves cost of filters, additives and staff time
10) Shortened postoperative intensive care period

Presentation of Custodiol HTK solution

5 litre bag (cartons of 2 bags)

2) 2 litre bag (cartons of 4 bags)
3) 1 litre bottle (cartons of 6 bottles)
4) 500 ml bottle (cartons of 10 bottles)

The Custodiol bag, Cryovac M312, is made of a new generation of

advanced films for medical solutions. The material is based on
exclusive multilayer technology resulting in a film that is
exceptionally clear, extremely durable with a wide range of superior
physical properties.

Storage
8 15 C
 Shelf-Life
1 year

St.THOMAS CARDIOPLEGIC SOLUTION

The original St. Thomas' Hospital cardioplegic solution (now termed St.
Thomas' Hospital cardioplegic solution No. 1 [STH1]) was developed in the
early 1970s by Hearse and colleagues and was first used clinically in 1976 .
Continuing experimental development of the solution resulted in a refined
formulation, which became commercially available under the name of
Plegisol (St.Thomas' Hospital cardioplegic solution No. 2 [STH2]).
This solution was approved by the Food and Drug Administration for use in
the United States and remains the most widely used crystalloid cardioplegic
solution in the world. Continuing experimental studies have shown
that STH2 is substantially more eficacious than STH1 in terms of both
myocardial protection and antiarrhythmic effects . Despite the evidence that
STH2 provides better myocardial protection, commercial cost implications
have meant that STH1 is used in the majority of cardiac centers in the
United Kingdom and in some European units in preference to STH2.
Addition of exogenous high-energy phosphate compounds, like many other
metabolic additives, has been shown to confer beneficial, despite
controversy regarding the ability of these compounds to enter the cell. Thus,
creatine phosphate (CP) alone or in combination with adenosine triphosphate
(ATP) when used as an additive to STH2 enhanced the protective properties
of STH2 in terms of both function and antiarrhythmic effects. These
experimental studies were confirmed clinically but only at the cellular level
and not on clinically measurable variables. We hypothesized that the use of
CP as an additive to STH1 might considerably enhance the myocardial
protective properties of that solution. Differences might be detectable in
terms of post ischemic function, reperfusion-induced arrhythmias, or both,
and previously observed changes at the cellular level should also be
 observed. The aim of the present study was to determine in a clinical study
whether the addition of CP to STH1 could enhance the protective effect of
STH1

COMPOSITION:

COMPOUND CONCENTRATION
(mmol/L)

SODIUM CHLORIDE 144.0

POTASSIUM CHLORIDE 20.0
MAGNESIUM CHLORIDE 16.0
CALCIUM CHLORIDE 2.4
PROCAINE HYDROCHLORIDE 1.0
Ph 5.5-7.0
OSMOLARITY (mosm)/kgH2O 300-320

DEL NIDO CARDIOPLEGIA SOLUTION

The del Nido cardioplegia contains a base solution of Plasma-Lyte A, which has an
electrolyte composition similar to the extracellular fluid (Baxter Healthcare
Corporation, Deerfield, IL). The concentrations of electrolytes before the addition
of cardioplegic additives are 140 mEq/L sodium, 5 mEq/L potassium, 3 mEq/L
magnesium, 98 mEq/L chloride, 27 mEq/L acetate, and 23 mEq/L gluconate. The
manufacturer lists a pH value of 7.4. The cardioplegia additives to this base
solution, This formulation serves as the crystalloid component, which is mixed
with blood in a ratio of four parts crystalloid to one part fully oxygenated patient
whole blood (usually obtained from the bypass circuit). It is important to note that
there is no calcium in the base solution. The final calcium concentration of this
cardioplegia can be described as trace because 20% of the delivered volume
contains patient blood. This is an important consideration because trace of calcium
in cardioplegic solutions has been shown to be preferable as compared with
acalcemic or normal levels

1 L Plasma-Lyte A base solution to which the following are added:

Mannitol 20%, 16.3 mL

Magnesium sulfate 50%, 4 mL

Sodium bicarbonate 8.4%, 13 mL

Potassium chloride (2 mEq/mL), 13 mL

Lidocaine 1%, 13 mL

Mannitol
Myocardial injury during cardioplegic arrest and subsequent reperfusion may be in
part the result of oxygen-free radicals including superoxide anion, hydrogen
peroxide, and hydroxyl. These radicals are normally countered enzymatically
within the cell but this is inhibited during myocardial arrest . Additionally,
myocardial edema has also been implicated in post ischemic myocardial
impairment. Hyperosmotic mannitol has been shown to both scavenge free radicals
and reduce myocardial cell swelling. To note, at Boston Childrens Hospital, we
also deliver .5 g/kg mannitol to the bypass circuit shortly before the removal of the
cross-clamp owing to these properties and also its osmotic diuretic effects.
 Magnesium Sulfate
Myocardial function is intimately related to intracellular calcium concentration.
The normal calcium flux in the myocardium increases intracellular calcium for
contraction and decreases it for relaxation. If calcium is allowed to accumulate in
the myocardium, relaxation may be interrupted and diastolic stiffness with poor
recovery may result . Magnesium has been shown to be a natural calcium channel
blocker . This effect is likely how magnesium has been shown to improve
ventricular recovery in hypothermic cardioplegia solutions when coupled with a
low calcium level .

Sodium Bicarbonate
Aerobic metabolism is not usually possible for the entire myocardial arrest period.
Therefore, anaerobic glycolysis must be supported. Anaerobic glycolysis and its
production of ATP has been shown to be inhibited by excess hydrogen ion
accumulation. The del Nido cardioplegia mix incorporates sodium bicarbonate as a
buffering solution to scavenge excess hydrogen ions and to assist in maintaining
intracellular pH. It is also important to note that red blood cells contain a high
concentration of carbonic anhydrase, an enzyme that facilitates the scavenging of
hydrogen ions with bicarbonate to generate carbon dioxide and water. This
property of red blood cells may in fact be its most important role in cardioplegia.

Potassium Chloride
Hyperkalemia is the most common arresting method for cardiac surgery because it
provides rapid arrest and reliable recovery but it has been shown to have
limitations. It provides a depolarized arrest. Depolarized arrest has been associated
with poor myocardial recovery as a result of intracellular sodium and calcium
accumulation during the arrest period . Lidocaine likely inhibits these negative
effects while enhancing the period of time in which electromechanical activity is
absent. The potassium level in del Nido cardioplegia is 24 mEq/L (see subsequent
equation).
(0.8 crystalloid component)(26 MEQ added K* + 5mEq Plasmalyte K**)+ (0.2 bl
ood component) (4.5 mEq/L K***) = 24 mEq/L K+
* Potassium added to the plasmalyte base solution 13 ml or 26 mEq. Total
solution volume 1059ml.
** 5mEq is the potassium concentration in the Plasmalyte base solution used
to formulate the del Nido solution.
*** 4.5 mEq/L is an estimate of the patients serum potassium level

Lidocaine
Lidocaine is classified as a sodium channel blocker and is a frequently used
antiarrhythmic. Sodium channel blockade increases the refractory period of the
cardiac myocyte . When cardioplegia is given in an ideal environment without
washout, this action is prolonged because the lidocaine remains in adequate
concentrations to continually affect the myocardium. Additionally, sodium channel
blockade helps counteract the negative effects of a hyperkalemic depolarized arrest
by polarizing the cell membrane to some degree and preventing sodium and
calcium accumulation within the cell. Depolarized arrest can allow for sodium and
calcium accumulation through exchange mechanisms and blocking the sodium
channels helps prevent this. A 2009 study by OBrien et al. showed that del Nido
cardioplegia reduced calcium accumulation during myocardial ischemia in a
setting of a depolarized arrest. It may be helpful to note that del Nido cardioplegia
can therefore be classified as a modified depolarizing agent, primarily as a result of
the properties of lidocaine and magnesium.
Patient Blood Additive
The del Nido cardioplegia is delivered with 20% by volume fully oxygenated
patient blood, which supports aerobic metabolism for a finite period of time and
provides buffering properties to promote anaerobic glycolysis as well. Blood in
cardioplegia has also been shown to improve coronary perfusion during
cardioplegia delivery . Furthermore, studies have shown blood cardioplegia to
preserve myocardial metabolism and function and result in less metabolic
ischemic stress and reperfusion injury when compared with sanguineous
cardioplegia in a varied population of patients undergoing congenital heart surgery
The cardioplegia hematocrit can be calculated by multiplying the blood component
hematocrit (drawn from the bypass circuit) by the 20% portion. The delivery
hematocrit of del Nido cardioplegia will be 6% if the 20% blood portion has a
hematocrit of 30% (.3 bypass circuit hematocrit +.2 portion of cardioplegia mix =
hematocrit of 6%).

Hypothermia
Decreasing the myocardial metabolic rate with hypothermia is a common practice
for cardioplegia delivery . Hypothermia decreases oxygen and high-energy
phosphate consumption while providing its own additional cardioplegic effect at
low temperatures . In our circuit, the del Nido cardioplegia passes through a
cooling coil in ice. The delivery temperature with this simple method is usually 8
12C.

Dose
The del Nido cardioplegia solution is generally given as a single 20-mL/kg dose.
The maximum arresting dose is usually limited to 1 L for patients larger than 50
kg. Additional cardioplegia volume may be given for hypertrophied hearts, those
with aortic insufficiency, or those with known coronary disease based on the
effectiveness of the initial dose and surgeon preference. A smaller arresting dose of
10 mL/kg may be used for procedures requiring a cross-clamp time less than 30
minutes. Subsequent doses are not normally given except for the rare occurrence of
electrical activity or for exceptionally long cross-clamp times (greater than 3
hours) at the surgeons discretion.
It is important to mix the crystalloid cardioplegia component correctly with the
patients blood to achieve the desired ratio of parts: four parts crystalloid to one
part patient blood. Clinically, we multiply the patients weight in kilograms by 20
mL/kg to get the total cardioplegia dose volume. We then add the circuit prime
volume of 150 mL and divide the total by five parts to arrive at the volume of the
blood component. Then, by taking the delivery dose volume, adding 25 mL to
account for the minimum reservoir level, and subtracting the blood component, we
arrive at the crystalloid volume that should be in the cardioplegia reservoir before
the addition of blood. Fully oxygenated patient blood is drawn off the bypass
circuit once the patient has been on the heartlung machine for at least 12
minutes. This precise volume is drawn from the bypass circuit through a manifold
syringe and then injected into the separate recirculating cardioplegia delivery
system. The result is that only the 20-mL/kg cardioplegia dose, plus the reservoir
minimum of 25 mL, is in the cardioplegia reservoir bag recirculating awaiting
delivery.

Delivery
Delivery is initiated with the surgeon moving the clamp on the table lines from the
outlet to the return limb. Flow is controlled at the heartlung machine by the
perfusionist. We generally give the 20-mL/kg cardioplegia dose over 12 minutes
with a system pressure of 100200 mmHg. We do not monitor aortic root pressure
although the surgeon monitors aortic root distention closely during delivery to
prevent capillary damage from high shear forces with too rapid a delivery. This
method results in a cardioplegia delivery flow rate of 1020 mL/kg/min in infants
and toddlers. In other words, it is clinically rather simple to estimate the initial
delivery rate by taking half of the arresting dose volume and using that as the flow
rate. For example, in a 12-kg patient, the dose volume would be 240 mL (20 mL/kg
cardioplegia 12 kg). An initial infusion rate of half that (120 mL/min) would be a
proper estimate to achieve an infusion rate of 12 minutes with a system pressure
of 100200 mmHg, at least with our custom cardioplegia circuit. The initial flow
rate for root administration is limited to 300 mL/min in larger patients. The initial
flow rate for ostial administration can be classified as barely on. Cardioplegia
flow for all methods is adjusted from the initial flow based on the surgeons
observation of the heart and electrical activity. Cardioplegia system pressures may
be higher with increased flows, smaller root needles, and ostial delivery. These
higher system pressures are not linearly related to root pressure, but it is still
imperative that the surgeon visually monitor delivery.

Temperature
del Nido cardioplegia is delivered cold. Myocardial oxygen consumption decreases
by 50% for every 10C decrease in myocardial temperature . The del Nido
cardioplegia is delivered at a temperature of 4C and will produce myocardial
cooling to less than 15C.

del Nido Cardioplegia May Initially Increase the Level of Hemodilution

del Nido cardioplegia is dosed at 20 mL/kg, up to 1000 mL for patients larger than
50 kg. When it is administrated to a small patient with a relatively low hematocrit
(HCT), the benefits of del Nido cardioplegia may be offset by the adverse effects
of hemodilution. del Nido cardioplegia, which drains from the coronary sinus, can
be suctioned into a cell saver instead of returning to systemic circulation when total
bypass (bicaval cannulation with caval occlusion) is performed and the right atrium
is opened. This method limits hemodilution and requires clear communication and
teamwork among surgeons, physicians assistants, and perfusionists. In cases in
which the right atrium is not opened and the cell saver cannot be used in the
manner described, hemoconcentration should be considered in small patients with
relatively low HCTs to maintain an acceptable patient hematocrit. However,
multiple doses of modified Buckberg cardioplegia can result in similar levels of
hemodilution.
BLOOD CARDIOPLEGIA
Currently ,blood cardioplegia is the preferred cardio protective strategy in the
United states and in most West European countries .The technical details of blood
cardiplegia have evolved as a consequence of experimental studies and clinical
application including multidose cold blood cardioplegia ,warm blood cardioplegic
reperfusion ,warm induction ,antegrade and retrograde delivery ,continuous cold
blood perfusion and intermittent warm blood cardioplegia .
The fact that blood cardioplegia has emerged as the preffered cardioprotective
strategy is based on its versality ,because a blood vehicle for cardioplegic delivery
blends onconicity ,buffering ,rheology ,and anti oxidant benefits with its capacity
to augment oxygen delivery and ability to resuscitate the heart, prevent ischemic
injury and limit reperfusion damage .
In detail ,the cardioprotective potential of blood cardioplegia is represented by the
synergistic effect of its different components :
Hyperkalemia :induction and maintenance of cardioplegic
arrest
Hypocalcemia :avoidance of mitochondrial calcium overload
and preventionof irreversible myocyte injury .
Tris buffer : prevention of tissue acidosis
Hypersomolarity and hyperglycemia : prevention of myocardial
edema
Glutamate and aspartate : these amino acids replenish key krebs
cycle depleted during ischemia by enhancing aerobic
metabolism and reparative process.

Warm cardioplegic induction

Warm blood cardioplegic induction (WBCI) improves recovery of cardiogenic

shock hearts by repaying their energy debt before cold ischemic arrest. This study
tests the hypothesis that despite the absence of shock, many hearts are energy
depleted and would benefit from WBCI. The concept of warm cardioplegia
induction was introduced to actively resuscitate the ischemically damaged ,energy
and substrate depleted heart by maximizing the kinetics of repair and minimizing
O2 demands by maintaining arrest .Therefore ,blood cardioplegia is supplemented
with the amino acids glutamate and aspartate to replenish Krebs cycyle
intermediates that are depleted in compromised hearts .Warm cardioplegic
induction is applied to patients in cardiogenic shock with severely impaired
ejection fraction or in acute myocardial infarction .

Normothermic blood cardioplegia is administered initially at 250 -300 ml/min via

the aortic root until cardioplegic arrest is achieved .Thereafter ,cardioplegic flow is
reduced to 150 ml/min .warm cardioplegic pressure is applied ante and
retrogradely (1min each).This is followed by cold cardioplegic standard blood
cardioplegia .

Blood cardioplegia in heart transplantation

We use leucocyte depleted blood cardioplegia and start with first retrograde
administration after the heart is removed from the storage solution .The
coronary sinus catheter is introduced and secured with a prolene pursestring
suture usuing a tourniquet .Initially ,cold blood cardioplegia is administered
for 3 min .The second application of cold blood cardioplegia (2mins)is
performed after 20 mins .The third application is a warm terminal
reperfusion with leucocyte depleted and substrate enriched blood
cardioplegia for 45 s. Retrograde perfusion is continued with normothermic
leucocyte filtrated blood .The aortic clamp is released as the first filtrated
blood .The aortic clamp is released as the first contractions of the
transplanted heart become visible .

BLOOD CARDIOPLEGIA LEUCOCYTE FILTRARTION

Myocardial ischemia and reperfusion are associated with activation of

neutrophils and expression of adhesion molecules on the myocardial
endothelium surface .In the case of long cross clamp time ,acute myocardial
infarction ,or in heart transplantation ,activated leucocyte in blood
cardioplegia or initial reperfusate may cause significant myocardial
damage .Clinical studies have demonstrated the benefit of blood
cardioplegia filtration in patients undergoing emergency coronary bypass
surgery or prolonged cross clamping ,in patients with depressed ejection
fraction ,and in heart transplantation .Experimental studies have shown that
atleast 90%of leucocytes must be removed to attenuate reperfusion injury
markedly .In addition ,leucocyte depletion should be maintained for 5-10
min after the start of intial reperfusion prior to aortic clamp release
.Commercially available blood cardioplegia filters remove more than 90%of
the leucocytes up to total volume of 1500 mlof blood cardioplegia .
OTHER CURRENT TECHNIQUE USING BLOOD CARDIOPLEGIA

In addition to the classic standard technique of blood cardioplegia several

modifications have evolved and are used in different centres

Continuous warm blood cardioplegia

The goal of this technique is to prevent any myocardial ischemia
during aortic cross clamping by continuous retrograde delivery of
warm cardioplegia . How ever most surgeons discontinue cardioplegic
flow for few minutes during construction of the distal anastomoses
leading to unintential myocardial ischemia .In addition ,cardioplegic
overdose is a potential problem using this technique

INTERMITTENT ANTEGRADE WARM BLOOD CARDIOPLEGIA

This concept was published by calafiore in 1995 and had been
developed to eliminate the problem of blood in the operative field
when using continuous warm blood cardioplegia .Normothermic
blood is mixed with a K+ solution using a syringe pump. Repeated
doses are delivered after 15 mins .Hypothermia is completely
avoided .The presence of critical coronary stenosis limits the delivery
of antegrade cardioplegia to ischemic regions of the heart ,particularly
when revascularization with the internal mammary artery prevents
vein graft infusions to the left anterior descending artery .This
inadequate cardioplegic delivery using only the antegrade route may
induce warm ischemic injury .
 TEPID BLOOD CARDIOPLEGIA
Ante grade tepid blood cardioplegia was introduced by the Toronto
group to combine the advantages of warm and cold blood cardioplegia
and to minimize the detrimental effects of blood cardioplegia
.Reducing the hearts temperature from 37degree to 29degreeC did not
alter myocardial oxygen consumption but did reduce myocardial
lactate release.

CARDIOPLEGIA IN PEDIATRICS

Cardioplegia has become the gold standard of myocardial protection for

practically every type of heart surgery during which the ascending aorta
must be clamped. Although there is little doubt about the efficacy of
cardioplegia in the adult heart, there are few studies on the pediatric heart
and their results are contradictory. The physiology of pediatric heart muscle
differs considerably from that of the adult myocardium. The pediatric heart
distinguishes itself from that of the adult most impressively in its greater
tolerance for ischemia. This ischemia tolerance is enhanced by the use of
hypothermia. Considering that hypothermia is a powerful tool to prolong
ischemia tolerance and that most pediatric cardiac surgeons report similar
results using different types of cardioplegia, some surgeons are tempted to
suspect that the contribution of the cardioplegia composition to protecting
the pediatric heart may be overestimated. This provocative statement is
critically discussed in this article. We examine the protective potential of
cardioplegia (in various compositions), or of hypothermia, or of both in
pediatric cardiac surgery. We pay special attention to several key differences
between the physiologies of the pediatric myocardium and the adult
myocardium and attempt to relate them to the available surgical methods of
myocardial protection. We conclude that the composition of cardioplegia
indeed is an important component of successful operative management in
pediatric heart surgery. We provide evidence that the benefit of cardioplegia
over hypothermia alone is minor at low temperatures (below 15C), but
becomes substantial when the temperature increases.

The main principles of myocardial protection are the reduction of metabolic

activity by hypothermia and the therapeutic arrest of the contractile
apparatus and all electrical activity of the myocytes by administering
cardioplegic solution (eg, depolarizing of the membrane potential by high
potassium blood cardioplegia) . Both principles are unequivocally accepted
and result in the decrease of energy consumption. By reducing energy
consumption and thus oxygen demand, ischemia tolerance of the heart can
be significantly prolonged. Without such measures, irreversible ischemic
damage begins to occur in the human heart after only 20 min whereas when
current techniques of myocardial protection are used, arrest times of more
than 4 or 5 hours may be tolerated without irreversible damage (eg, 4 to 5
hours of myocardial ischemia is not uncommon during heart
transplantation . In addition to these two major principles, other means of
extending the hearts ischemia tolerance have been advanced, tested, and
applied, but are discussed much more controversial. These approaches
consist of buffering the cardioplegic solution, increasing osmolality,
decreasing calcium content adding substrate to enhance recovery or
incorporating leukocyte filters in the cardiopulmonary bypass circuit
In 1984, Bull and colleagues presented a landmark study demonstrating the
efficacy of cardioplegia in pediatric cardiac surgery. Since then the
achievements in this field have been tremendous and have set the ground for
current practices in pediatric cardiac surgery with outstanding results. If
these results are so clear, why is the efficacy of cardioplegia questioned for
the heart in development? Doubts are based on several reasons: Poor
myocardial protection is still considered a significant cause for in-hospital
mortality in children the neonatal heart has a significantly greater tolerance
for ischemia the results on the efficacy of cardioplegia in the pediatric
population are contradictory hypothermia alone (by lowering perfusate
temperature below 15C) results in the arrest of contractile activity . Most
pediatric cardiac surgeons report similar results using different strategies of
myocardial protection as adjunct to hypothermia .The last reason, which also
applies to the adult heart, is impressively documented by the fact that 167
different cardioplegic solutions are clinically used for heart transplantation
in the United States alone .

The ischemia tolerance of the pediatric heart is significantly greater than that
of the adult heart. During cold cardioplegic arrest of the pediatric heart,
ischemia tolerance is primarily prolonged by hypothermia. The degree of
this time frames extension is maximal at myocardial temperatures under
15C. The use of cardioplegia is of great importance to the safe conduct of
pediatric cardiac surgery because it is difficult to guarantee continuous deep
hypothermia of the myocardium under practical conditions. Cardioplegia
contributes to the protection of the heart at higher temperatures and older
age. Therefore it provides an important margin of safety for every cardiac
operation with cardiac arrest. The ability to improve the current techniques
of myocardial protection is intimately linked to the understanding of the
underlying basic mechanisms.
CONCLUSION
Blood cardioplegia is an effective and widely accepted method of
myocardial protection .Retrograde cardioplegic delivery has been found to
be useful in enhancing even distribution of cardioplegia ,particularly distal to
coronary stenosis in vessels supplying the left ventricular myocardium
.Replenishment of substrates to the energy depleted heart is a main focus of
development for cardioplegia formulations ,designed to enhance recovery
following the ischemia required to carry out cardiac operations.

Integrated myocardial management is an easy and effective method of

myocardial protection in adult cardiac procedures by expediting the
operation and meeting the physiological needs of the myocardium .The
duration of cardiopulmonary bypass is shortened by this technique by
eliminating the need for recovery time following unclamping of the aorta
.Excellent clinical outcomes have been reported and this method has been
employed in many centres for the several years .

Ongoing studies are needed to develop additional cardioprotective

strategies ..These may include the use of preconditioning agents ,white
blood cell filter ,free radicals scavengers and endothelium enhancing agents
.
BIBILOGRAPHY
1. Cardiopulmonary bypass Sunit Ghosh, Florian Falter, David J. Cook
2. Myocardial protection Tomas A. Salerno, MD and Marco Ricci
3. Cardiopulmonary bypass Glenn P Gravlee, Richard F. Davis, Alfered H
Stammers, Ross M. Ungerleider