NATIONAL BOARD OF EXAMINATIONS IN MEDICAL SCIENCES NEW DELHI

THESIS PROTOCOL FOR DrNB CARDIAC ANAESTHESIA

THESIS TOPIC

“Use ofDel Nido Cardioplegia in Paediatric Cardiac Surgery – Our experience”

NAME OF CANDIDATE

Dr. JASJOT SINGH

DrNB SUPER SPECIALTY (CARDIAC ANAESTHESIA)

FORTIS HOSPITAL

SECTOR 62, PHASE-VIII

MOHALI, PUNJAB - 160062

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INVESTIGATOR : Dr. jasjot singh

DrNB CARDIAC ANAESTHESIA RESIDENT

DEPARTMENT OF CARDIOTHORACIC AND

VASCULAR ANAESTHESIA

FORTIS HOSPITAL, MOHALI, PUNJAB – 160062

GUIDE : Dr. ALKA RANI KOCHAR

ADDITIONAL DIRECTOR

DEPARTMENT OF CARDIOTHORACIC AND

VASCULAR ANAESTHESIA

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 FORTIS HOSPITAL, MOHALI, PUNJAB – 160062

CO – GUIDE : Dr. MANORANJAN SAHOO

DIRECTOR AND HEAD OF DEPARTMENT

DEPARTMENT OF CARDIOTHORACIC AND

VASCULAR ANAESTHESIA

FORTIS HOSPITAL, MOHALI, PUNJAB - 160062

STUDY SITE: DEPARTMENT OF CARDIOTHORACIC AND

VASCULAR ANAESTHESIA

FORTIS HOSPITAL, MOHALI, PUNJAB - 160062

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INTRODUCTION

The main objective of cardioplegia is to lower the myocardial oxygen demand by cooling the heart

and inducing electrical quiescence, which lessens the ischemic effects of bypass. Cardioplegia

offers a generally bloodless and motionless surgical field, along with being cardioprotective.

There are numerous variations of cardioplegia, including retrograde and antegrade injection,

The delivery of cardioplegia is monitored barometrically to avoid the risk of endothelial cell

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destruction and reperfusion injury caused by high infusion pressures. The patient is

heparinized, cooled and when appropriate, is placed on cardiopulmonary bypass. Adequate

cardioplegic distribution protects cell damage.1

The idea behind cardioplegic solutions is to increase the resting membrane potential,
generally established by hyperkalemic solution. The search for the optimal cardioplegic
treatment is constantly ongoing.

In the 1990s, Pedro Del Nido and his colleagues at the University of Pittsburgh created Del
Nido cardioplegia. A particular cardioplegic solution was created keeping the needs and
peculiarities of paediatric myocardium on focus. Since 1994, Boston's Children Hospital has
performed pediatric heart surgery using this blood-based solution.

Del Nido cardioplegia is an extracellular solution combined with blood. There is a

crystalloid: blood ratio of 4:1. This means the crystalloid solution makes up 80% of the

solution. The crystalloid solution includes Plasma-Lyte as a basic solution, mannitol,

magnesium sulfate, bicarbonate, potassium and lidocaine.2

Mannitol serves as cell membrane regulator. Magnesium sulfate functions as calcium

antagonist. Sodium bicarbonate acts as buffer. Potassium chloride for myocardial arrest in

diastolic phase. Lidocaine, a class IB antiarrhythmic as a sodium channel blocker.

Reduction in myocardial injury postoperatively, and spontaneous conversion to normal sinus

rhythm are the main advantages of this solution.3 Additionally, there is reduction in the

insulin requirement when compared to the crystalloid solution likely due to the exclusion of

glucose in solution. Del Nido provides approximately 60 to 90 minutes of myocardial

protection; however, care must be taken, and redosing may be required in patients with left

ventricular hypertrophy or cases of severe obstructive coronary artery disease.4

Del Nido cardioplegia for infants and children is dosed at 20 mL/kg at a temperature of 8 to

12 degrees celsius in an anterograde fashion. Redosing is required depending on the length of

the procedure. Few factors to take care are to maintain cardiac arrest, pH, and the delivery of

substrates, wash the byproducts of anaerobic metabolism and reduce edema.

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It is essential to understand the electrolyte abnormalities, myocardial stunning, pH imbalance

that may occur secondary to cardioplegia administration. Before coming off cardiopulmonary

bypass, electrolytes, temperature, glucose, pH, hemoglobin, and hematocrit must be within

normal limits. Derangement of which may result in myocardial stunning, arrhythmias,

ischemic injury leading to inability to wean off from cardiopulmonary bypass.

A good understanding of the various components, routes of administration, dosage and

potential side effects of cardioplegia solution is necessary to reduce morbidity and mortality

REVIEW OF LITERATURE

Sameer Mohammed et al (2022), in this study, compared clinical results for neonates having

heart surgery using the St. Thomas II solution and Del Nido cardioplegia. Retrospective

analysis was performed on all newborns (less than 30 days) who underwent surgery that

required cardioplegic arrest between 2011 and 2017. Group A (Blood cardioplegia with n =

56) and group B (Del Nido cardioplegia, n = 48). The use of Del Nido cardioplegia solution

in newborns is linked with significant reduction in cardiopulmonary bypass and aortic cross

clamp times as well as VIS in the first 24 hours following surgery when compared to St.

Thomas solution. The selection of cardioplegia (St. Thomas/Del Nido) in neonates has no

effect on early postoperative clinical outcomes or early mortality.1

Alwaleed Al-Dairy et al (2023) aimed to add to the body of literature by discussing the

experiences of 86 young patients who underwent heart surgery at their facility. In a

retrospective analysis, they assessed 86 children with congenital heart abnormalities who had

Del Nido cardioplegic solution used during corrective cardiac surgery. They concluded

that usage of Del Nido cardioplegia was linked to improved clinical outcomes and lower

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morbidity. With less repeated dosage, it can offer suitable cardiac protection for prolonged

cross clamp periods.2

Luiz Fernando Caneo et al (2021) compared normal multidose cardioplegia protocol with a

del Nido cardioplegia for outcome in congenital heart surgery.250 patients in each group

were included in this retrospective single-center study. Age, weight, gender, and Risk

Adjustment for Congenital Heart Surgery (RACHS-1) scores were used to match groups. The

following outcomes were examined: bypass and aortic cross-clamp timings, lactate levels,

ventilation time, ventricular dysfunction with low cardiac output syndrome (LCOS), length of

stay in the intensive care unit, length of stay in the hospital, and in-hospital mortality. The

data provided evidence in support of del Nido cardioplegia solution.3

Maruti Haranal et al (2020) evaluated the efficacy and safety of blood-based St. Thomas

Hospital (BSTH) cardioplegia against del Nido cardioplegia for myocardial protection during

congenital heart surgery. Patients with both simple and complex congenital heart disorders

who had a left ventricular ejection fraction of at least 50% were included. A total of two

groups of 50 patients each were taken. Ventricular function and the spontaneous resumption

of cardiac activity after aortic cross-clamp release were the primary end goals. Myocardial

damage as determined by troponin T levels was the secondary end aim. Their research

revealed that in terms of myocardial protection, both the cardioplegia were similar. However,

del Nido cardioplegia is better suited for difficult repair because of its low volume and single

use.4

Barbara Brzeska et al (2023)compared two primary types of solutions, cold blood cardioplegia

and crystalloid cardioplegia, and researched to demonstrate their safety and effectiveness.

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They considered a wide range of clinical and biochemical factors that could signal the

effectiveness of cardioprotection and inferred that Del Nido offered better cardioprotecion. 5

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AIMS AND OBJECTIVES

The present study will be conducted in the Department of Cardiothoracic and Vascular

Anesthesiology, Fortis Mohali. The objectives of this dissertation are to study the outcomes

of Del Nido cardioplegia on

1Myocardium injury after the aortic cross clamp release, indidence and severity of Low

cardiac output sundrome(LCOS) and markers of reduced tissue perfusion

2.Total aortic cross-clamp time

3Need for internal defibrillation during reperfusion

4 Duration of mechanical ventilation

6 Length of post operative stay in pediatric intensive care unit

7. Delayed sternal closure, incidence and duration

8. Unplanned reoperation, including chest re-opening in PICU

9. Need for new renal replacement therapy

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MATERIALS AND METHODS

Study Site: the present study will be conducted in the department of Cardiothoracic and
Vascular Anesthesiology, Fortis Mohali, India
Study design: Hospital based prospective observational study
Study period: Within 2 years of the Ethical committee approval
Sample Size: It will be 100 patients

SELECTION OF PATIENTS
Inclusion Criteria:
1.Patients with congenital heart diseases (CHD) requiring
repair which involves aortic cross-clamping.
2. Congenital heart disease with normal ventricular function

3. Patients with a legally acceptable representative capa-

ble of understanding the informed consent document
and providing consent on the patient’s behalf
4. Age 0 to 12 years
5. American Society of anesthesiologists grades 3 and 4
Exclusion criteria:
1. Guardians who refuse to participate in the study

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2. Patients with impaired or poor ventricular function
3. American Society of Anesthesiologists grades 5 and 6
4. age above 12 years
5. Aortic cross clamp time exceeding 90 minutes
6. patients with preoperative arrythymia/heart block
7. patients with renal, hepatic and pulmonary disease

A thorough medical evaluation of all

patients done includ-
ing history of the disease and
treatment, current symptoms,
known drug allergies, assessment of
allergy, cardiovascular,
neurologic, respiratory, and surgical
history. Age at operation,
weight, height, and an assessment of
the organ systems with
any detectable abnormalities were
recorded. All patients under-
went thorough preoperative 2D
echocardiography with docu-
mentation of ventricular function
STUDY METHOD:

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A thorough medical evaluation of all patients will be done including history of the disease

and treatment, current symptoms, known allergies and its assessment, cardiovascular,

neurologic, respiratory, and surgical history. Age at operation, weight, height, and an

assessment of the organ systems with any detectable abnormalities will be recorded. 2 All

patients will undergo preoperative echocardiography with documentation of ventricular

function

Conduct of Cardioplegia: Cardioplegia solution will be prepared by the in-house pharmacy in

accordance to the Boston Children’s Hospital Sterile compounding standard operating

procedure.2 The solution is kept in refrigerator at 2 to 8 degree celsius temperature and used

before the expected expiry date. The crystalloid cardioplegia component will be mixed with

the patient’s blood directly drawn from the cardiopulmonary bypass circuit via a slave pump

to achieve a ratio of four parts crystalloid to one part blood. The amount of plegia required

will be calculated as per patient’s body weight.4

The del Nido cardioplegia solution will be given as a single 20 mL/kg dose. A smaller

arresting dose of 10 mL/kg will be considered for procedures requiring less than 30 minutes

of aortic cross-clamping. The maximum arresting dose will be limited to 1 L for patients

larger than 50 kg. Additional cardioplegia volume may be given for hypertrophied hearts,

those with aortic regurgitation based on the effectiveness of the initial dose and surgeon

preference. Delivery will be initiated by the surgeon when the cross-clamp is applied. Flow is

controlled at the heart–lung machine by the perfusionist Dosage used will be 20 mL/kg over a

few minutes or longer if the volume infusion is larger. Repeat dose is given if the aortic cross

clamp time exceeds 60 minutes at 10 ml/kg.4 No aortic root pressure is monitored but surgeon

monitors aortic distension closely during the delivery to avoid capillary leakage from high

shear forces.

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Surgery using median sternotomy with aortic and bicaval cannulation will be done.

Additional myocardial protective measures such as topical cooling and systemic hypothermia

will be employed in all patients. Intraoperative parameters will be monitored including

operation performed, aortic cross-clamp time, temperature on bypass, cardiopulmonary

bypass duration, time for heart activity to return after cross-clamp is removed, and number of

plegia required. Hematocrit levels will be regulated during cardiopulmonary bypass and

regular intervals sampling of blood for blood gas analysis. The first one done prior to

commencement of bypass, during bypass, at rewarming, and after protamine is administered.

Arterial blood gas will be done to check for the potassium and calcium levels before the

termination of CPB, any abnormalities detected will be corrected. All the study subjects are

to receive elective inotropic support. In our study, after the cross-clamp will be removed,

heart contraction resumed with ventricular activity is taken as spontaneous return of activity.

Rhythm is recorded as heart block when patients required temporary pacing at the time of

termination of cardioplulmonary bypass. After the termination of cardioplulmonary bypass ,

a thorough transesophageal echocardiography will be done to address any significant residual

structural intracardiac lesions. We will use left ventricular ejection fraction as an indicator of

cardiac function, which will be measured by Transesophageal echocardiography after

termination of cardioplulmonary bypass. Prior to the measurement of left ventricular ejection

fraction, we will rule out reversible causes of myocardial dysfunction such as electrolyte

abnormalities and residual cardiac lesions in all patients which may confound the overall

cardiac function.

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 Low cardiac output syndrome (LCOS) defined as either of the following in the first 48

hours after reperfusion: Vasoactive Inotrope Score (VIS) ≥15, or major cardiac event

(cardiac arrest, ECLS or death)

VIS will be calculated using the formula: dopamine dose [μg kg−1 min−1]+dobutamine

[μg kg−1 min−1]+100×epinephrine dose [μg kg−1 min−1]+ 10×milrinone dose [μg

kg−1 min−1]+10 000×vasopressin [units kg−1 min−1]+100×norepinephrine dose [μg

kg−1 min−1]6

Duration of mechanical ventilation (hours), defined as the number of hours from

termination of CPB to extubation

Length of postoperative stay on Paediatric Intensive Care (hours), defined as number of

hours from admission to PICU from theatre following procedure to discharge from PICU

VIS score at the end of the surgery.

Max VIS by thresholds: ≥10, ≥15 and ≥20 in the first 48 hours will also be noted

Arterial lactate (mmol/L) after protamine and 6-12 hours from aortic cross clamp release
will be noted
Total aortic cross-clamp time (mins)
Total volume of cardioplegia given (ml)
Need for internal defibrillation during reperfusion and the number of times its attempted
Delayed sternal closure, we will observe incidence(number) and duration (days)
Unplanned reoperation, including chest re-opening in PICU (number)
Need for new renal replacement therapy in first 72 hours post aortic cross clamp release

Length of postoperative stay in the hospital (days), defined as number of days from day of

surgery to discharge from hospital or death, whichever is sooner

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Left ventricular function will be assessed by pre and post operative transesophageal

echocardiography

STATISTICAL ANALYSIS:

Baseline and outcome data shall be recorded in a pre-designed proforma. Statistical

analysis shall be done using test given in Statistical Package for Social Scientist

(SPSS) 20. Continuous variable will be presented as mean or mean and standard

deviation (SD) (95% confidence interval). Chi-square will be used to evaluate the

association between categorical variables. A p-value of <0.05 will be considered

statistically significant. Relative risk of adverse outcome shall also be calculated.

ETHICAL CONSIDERATION

Guidelines set up by ICMR (1994) and Helsinki Declaration (modified, 1989) will be

adhered to with all patients, and volunteers involved in the study

Informed and written consent (in the language they best understand) will be taken
from each subject before collecting data. Only those individuals, who volunteer
to participate in the study, will be included and the data will be kept confidential.
The study will not impose any burden on the subjects and the Institute; therefore,

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 the study is ethically justified. The proposed study will be undertaken to approval
by Institutional Ethical Committee.

DATA COLLECTION FORM

Name: …………………. …….. UHID no:……………………….

Age: …………….. Sex: ……………….

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Weight:………….Kgs Height:………..

Date of admission: ……………… Date of discharge:………………..

Date of surgery: ………..

Preoperative Left Ventricular Function:……….

Intraoperative:

Cardioplegia: anterograde/retrograde/both

Cardiopulmonary bypass time(min):

Aortic Cross Clamp time(min):

Cardioplegia:- Volume(ml): Number of times plegia given:

Need for defibrillation during reperfusion: yes/no

If yes:- Number of times

Vasoactive inotropic score:-

Score more than 15 after reperfusion yes/no

At the end of the surgery:

Arterial lactate(mmol/l):

Any major cardiac event after reperfusion:

Postoperative:-

Vitals:on shifting to surgical intensive care unit

BP …………….

Pulse ……../minute

RR ………../ minute

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SpO2 …………..

Postoperative ventricular function:

Vasoactive inotopic score at 1 hour:

Vasoactive inotropic score at 24 hours:

Vasoactive inotropic score more than 10 in first 48 hours:

Vasoactive inotropic score more than 15 in first 48 hours:

Vasoactive inotropic score more than 20 in first 48 hours(number):

Any major cardiac event within 48 hours:

Arterial lactate at;- 6 hours:

Delayed sternal closure(days)

Unplanned reoperation

Renal replacement therapy in 72 hours:

Length of mechanical ventilation(hours)

Length of surgical intensive care unit stay(hours):

Length of postoperative stay in hospital(days):

REFERENCES:
1 Mohammed S, Menon S, Gadhinglajkar SV, Baruah SD, Ramanan SV, Gopalakrishnan
KA, Suneel PR, Dharan BS. Clinical outcomes of del nido cardioplegia and st thomas
blood cardioplegia in neonatal congenital heart surgery. Ann Card Anaesth. 2022 Jan-
Mar;25(1):54-60

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 2 Al-Dairy, Alwaleed. (2023). Recent Experience in the use of Del Nido Cardioplegic
Solution in Pediatric Patients. International Clinical and Medical Case Reports. 2.
10.59657/2837-5998.brs.23.010
3 Caneo LF, Matte GS, R Turquetto AL, et al. Initial experience with del Nido

cardioplegia solution at a Pediatric and Congenital Cardiac Surgery Program

in Brazil. Perfusion. 2022;37(7):684-691

4. Haranal M, Chin HC, Sivalingam S, et al. Safety and Effectiveness of Del

Nido Cardioplegia in Comparison to Blood-Based St. Thomas Cardioplegia in

Congenital Heart Surgeries: A Prospective Randomized Controlled

Study. World Journal for Pediatric and Congenital Heart Surgery.

2020;11(6):720-726

5 Brzeska, Barbara & Karolak, Wojtek & Żelechowski, Paweł & Los, Andrzej & Ulatowski,
Nikodem & Pawlaczyk, Rafał. (2023). Del Nido cardioplegia versus other contemporary
solutions for myocardial protection – a literature review. European Journal of
Translational and Clinical Medicine. 6. 41-57. 10.31373/ejtcm/163317

6 Kumar M, Sharma R, Sethi SK, Bazaz S, Sharma P, Bhan A, Kher V.

Vasoactive Inotrope Score as a tool for clinical care in children post
cardiac surgery. Indian J Crit Care Med. 2014 Oct;18(10):653-8

7 Dorfman AT, Marino BS, Wernovsky G, Tabbutt S, Ravishankar C,

Godinez RI, et al. Critical heart disease in the neonate: Presentation and
outcome at a tertiary care center. Pediatr Crit Care Med. 2008;9:193–
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8 Wernovsky G, Wypij D, Jonas RA, Mayer JE, Jr, Hanley FL, Hickey PR, et
al. Postoperative course and hemodynamic profile after the arterial
switch operation in neonates and infants. A comparison of low-flow
cardiopulmonary bypass and circulatory
arrest. Circulation. 1995;92:2226–35.
9 Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, et al.
Vasoactive-inotropic score as a predictor of morbidity and mortality in

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 infants after cardiopulmonary bypass. Pediatr Crit Care
Med. 2010;11:234–8.
10 Butts RJ, Scheurer MA, Atz AM, Zyblewski SC, Hulsey TC, Bradley SM, et

al. Comparison of maximum vasoactive inotropic score and low cardiac

output syndrome as markers of early postoperative outcomes after
neonatal cardiac surgery. Pediatr Cardiol. 2012;33:633–8.
11 Sethi SK, Goyal D, Yadav DK, Shukla U, Kajala PL, Gupta VK, et al.

Predictors of acute kidney injury post-cardiopulmonary bypass in

children. Clin Exp Nephrol. 2011;15:529–34.
12 Kotani Y, Tweddell J, Gruber P, et al. Current cardioplegia practice in pediatric

cardiac surgery: a North American multiinstitutional survey. Ann Thorac

Surg 2013; 96: 923–929.

13 Matte GS, del Nido PJ. History and use of del Nido cardioplegia solution at

Boston Children’s Hospital. J Extra Corpor Technol 2012; 44: 98–103.

14 Yamamoto H, Yamamoto F. Myocardial protection in cardiac surgery: a

historical review from the beginning to the current topics. Gen Thorac

Cardiovasc Surg 2013; 61: 485–496.

15 Charette K, Gerrah R, Quaegebeur J, et al. Single dose myocardial protection

technique utilizing del Nido cardioplegia solution during congenital heart

surgery procedures. Perfusion 2012; 27: 98–103.

16 Ler A, Sazzad F, Ong GS, et al. Comparison of outcomes of the use of Del Nido

and St. Thomas cardioplegia in adult and paediatric cardiac surgery: a

systematic review and meta-analysis. Perfusion 2020; 35: 724–735.

Chambers D J, Fallouh H B.
(2010). Cardioplegia
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Pharmacological arrest and
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global ischemia and
reperfusion. Pharmacology &
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3. Lazar H L. (2018). Del
Nido cardioplegia: Passing
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Hospital. (2012) The journal
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PATIENT INFORMATION SHEET

1. It is not compulsory for the patient to take part in the study.

2. In case the parents agree for their child to take part in the study, the parents will have to
agree to provide access to pre-operative, intraoperative, and postoperative records.

3. The parents will only have to provide demographic details, Clinical history, and consent
for clinical examination, preoperative, postoperative, and use of hospital records.
4. Since this is not an Interventional study, there are no side effects, risks, or discomforts of
taking part in the study.
5. There are no costs of taking part in the study.
6. Patient demographic data and medical records will be used for the study.
7. There is no scope for research-related injury, as this is an Observational study. Hence there
is no provision for any compensation.
8. Parents must contact the Principal Investigator, as mentioned on the Informed Consent
Form, on the Telephone number provided, in case they require more information or help.

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