REVIEW ARTICLE
Cardiopulmonary Bypass in Infants
Asli Dönmez, MD,* and Okan Yurdakök, MD†
T HE INCIDENCE OF congenital heart defects is approx-
imately 7 to 10 per 1,000 live births.1 With advancing
technology and improved diagnostic, surgical, anesthetic, and
and jeopardize systemic perfusion. In addition, development of
collateral vessels secondary to cyanosis and vascular obstruc-
tion may result in significant blood loss and impair surgical
postoperative management protocols, the tendency today is to field exposure.
perform the complete repair of defects early in infancy.1 Infants are characterized by a high metabolic rate and, thus,
Infancy is defined as the period from birth until age 1. The oxygen demand requiring higher flow rates per body surface
management of cardiopulmonary bypass (CPB) in infancy has area. Because they have limited cardiac and respiratory
many challenges and increased risk of morbidity and mortality reserves, in physiologically stressful circumstances rapid
compared with that of the adult population. Infants are more changes of pH, lactic acid, glucose levels, and temperature
prone to complications because of the immaturity of their organ may occur because of a compromised response to meet these
systems. There is a need for a more complete understanding of demands.
the anatomic, metabolic, and physiologic differences between Infants are prone to hypothermia because of their larger ratio
infants and adults, and patient care must be individualized of body surface area to weight and limited fat stores and have
considering the degree of hemodilution and hypothermia, acid- limited ability to deal with cold stress, which result in increased
base strategies, flow rates, circuit designs, priming the pump, oxygen consumption and may cause metabolic acidosis.7
and choice of cannulae.2 Neonatal myocardium is known for its immaturity compared
This review article outlines the differences between infants with the adult myocardium but is considerably more resistant to
and adults regarding their responses to CPB and reviews the ischemia. In the newborn, only 30% of the myocardial mass
main subjects like hypothermia, hemodilution, acid-base strat- acts as contractile tissue, compared with 60% of mature
egies, inflammatory response, extracorporeal circuit, and CPB myocardium. In addition, pediatric myocardium has fewer
protocols for infants. mitochondria, less oxidative capacity, and incomplete auto-
Since the first successful application of extracorporeal nomic innervations. Because the sympathetic innervations are
circulation in the 1950s,3 CPB has evolved and still is also immature, the control of vascular tone and myocardial
evolving, but basic concepts have remained the same: Oxy- contractility depends on adrenal function via catecholamines
genation and carbon dioxide elimination, perfusion, systemic rather than direct autonomic influences.8,9
cooling and rewarming, and removal of blood from the heart to As is well documented, the infant myocardium relies
provide a blood-free surgical field.4 On the other hand, despite heavily on glucose as its major substrate and also has a greater
clear understanding of the basic concepts and many improve- reliance on extracellular calcium for calcium-mediated excita-
ments, CPB management in infants still remains challenging tion coupling.10,11
and unique. The immature myocardium uses glucose as the main
substrate and also has an increased ability to utilize anaerobic
DIFFERENCES BETWEEN INFANTS AND ADULTS metabolism as well as an ability to metabolize fatty acids,
There are major differences between infants and adults ketones, and amino acids. Interestingly, 90% of ATP produc-
affecting their response to CPB (Table 1).5 Procedures per- tion in the mature heart is by the oxidation of the long chain
formed on infants and children may require the extreme fatty acids12 and not by utilization of glucose.
measures that are not necessary for adults, including deep The immature myocardium is a great deal more sensitive to
hypothermia, hemodilution, different acid-base strategies, low extracellular calcium levels than the mature myocardium. In
perfusion pressures, and wide variation of perfusion flow rates.
These measures notably vary from those of normal physiology
and affect protection of normal organ function during CPB. In From the *Department of Anesthesiology, Mugla University School
addition, their smaller circulating blood volume, higher oxygen of Medicine and the †Department of Cardiovascular Surgery, Turkey
consumption rate, reactive pulmonary vascular bed, immature Yuksek Ihtisas Hospital, Ankara, Turkey.
Address reprint requests to Asli Dönmez, Guniz Sokak, 23/19,
organ systems, and altered thermoregulation may cause vulner-
Kavaklidere, Cankaya, 06700, Ankara, Turkey. E-mail: aslidonmez
ability to deleterious effects of CPB in infants.6
@hotmail.com
The presence of large aorta-pulmonary collateral vessels or © 2014 Elsevier Inc. All rights reserved.
an interrupted aortic arch also necessitate changes in CPB 1053-0770/2601-0001$36.00/0
strategies and cannulation techniques. The cardiac pathology http://dx.doi.org/10.1053/j.jvca.2013.12.024
with large intra- and extracardiac shunts may result in a greater Key words: CPB, infants, hypothermia, hemodilution, acid base
redistribution of flow away from the vital organs during CPB strategies, inflammatory response, extracorporeal circuit
Journal of Cardiothoracic and Vascular Anesthesia, Vol ], No ] (Month), ]]]]: pp ]]]–]]] 1
, 2 DÖNMEZ AND YURDAKÖK
Table 1. Comparison of Adult and Pediatric CPB
Parameter Adult Pediatric
Minimum CPB temperature Rarely o251-321C Frequently 151-251C
Use of total circulatory arrest Rare Common
Pump prime
Dilution of blood volume 25%-33% 150%-300%
Whole blood or RBC added Rare Frequent
Perfusion pressure 50-80 mmHg 20-50 mmHg
Acid-base management strategy Alpha-stat pH-stat at temperature o281-301C
Glucose management
Hyperglycemia Frequent, requires insulin Less common
Hypoglycemia Rare Common, reduced hepatic glycogen stores
NOTE. Modified from DiNardo and Zvara.5
Abbreviations: CPB, cardiopulmonary bypass; RBC, red blood cells.
mature hearts, most of the calcium required for myocardial right-sided heart failure and may require extracorporeal sup-
contraction is provided by the sarcoplasmic reticulum, whereas port. Liquid ventilation, steroid use, and modified ultrafiltration
the sarcoplasmic reticulum is underdeveloped in the immature (MUF) seem to improve pulmonary function.6,7 MUF is highly
heart and has reduced storage capacity for calcium.13,14 The effective in reducing lung water and pulmonary morbidity.
activity of the sarcoplasmic calcium ATPase, the enzyme There are studies reporting that both the degree of hemodilution
responsible for calcium reuptake into the sarcoplasmic retic- and increased flow rates during CPB may cause worsening of
ulum, also is reduced relative to mature myocardium. There- lung injury.19,20
fore, the immature heart has lower intracellular calcium Renal dysfunction after CPB is another important cause of
concentration with a greater dependence on extracellular morbidity and mortality. The incidence of acute renal failure
calcium levels and is much more sensitive to calcium channel (ARF) varies between 0.7% to 59% depending on the complex-
blockers than the mature heart. Use of cardioplegic solutions ity of the surgical procedure.21–24 In the pediatric population,
containing normal or high calcium concentrations may have kidney function does not reach to adult level until the age of 2.7
detrimental effects, and use of solutions containing subphysio- Glomerular filtration rate is lower in neonates and infants
logic levels of calcium is recommended.15 Boston Children’s because of lower mean arterial pressure and high renovascular
Hospital’s experience shows that it is an advantage to have resistance. This results in impaired concentrating and diluting
very low levels of ionized calcium during the cooling phase mechanisms, sodium reabsorption and excretion, and acid-base
before aortic cross-clamping. There may be advantages in regulation. Use of CPB in infants is associated with higher fluid
having a lower ionized calcium level during hypothermic accumulation than adults, resulting in an increase in body water.
bypass as well. Therefore, calcium is not recommended to be The combined effects of hypothermia, nonpulsatile perfusion,
corrected until the later phase of rewarming.16 and lower mean arterial pressures may cause release of hormones
Immaturity also affects a number of enzymatic processes, like vasopressin, renin, angiotensin, and catecholamines, which
some examples of which are decreased antioxidant enzymatic leads to renal vasoconstriction and reduced renal blood flow
activity, causing the immature myocardium to be more resulting in oliguria and elevated serum creatinine levels.
susceptible to anaerobic metabolism, and decreased 5- Blinder et al25 retrospectively studied 430 infants (o90
nucleotidase activity, causing conversion of ATP to adenosine days old) who underwent congenital heart surgery. They used a
to decrease. In fact, the latter may explain why immature modified pediatric version of the Acute Kidney Injury Network
myocardium is more tolerant to ischemia.17 classification and found that postoperative acute kidney injury
Pulmonary dysfunction is common after CPB because lungs occurred in 52% of the infants: 31%, 14%, and 7% of infants
are still immature at birth and continue to grow and mature up reached acute kidney injury stage I, II, and III, respectively.
to 8 years of age. Lungs have 2 components, parenchymal and Single-ventricle status, CPB, and higher reference serum
vascular, and both of them serve as a source and target of the creatinine levels were associated with postoperative acute
inflammatory response during CPB.18 Both systemic inflam- kidney injury.25
matory response and ischemia/reperfusion injury during CPB Recently, significant interest has arisen regarding prevention
stimulate endothelial injury, resulting in capillary leak and of fluid accumulation and its possible positive influence on
extravasation of the fluid and the inflammatory cells to the mortality.26 The management of infants undergoing CPB is
parenchymal space and pulmonary edema, ending with poor focused on a negative total body water balance and, therefore,
oxygenation, reduced compliance, and reduced lung volumes. loop diuretics commonly are used to increase urine output.9
Patients with increased pulmonary blood flow may need intense Furosemide (1-2 mg/kg) or ethacrynic acid (1 mg/kg) every 4
medical therapy preoperatively to reduce pulmonary conges- to 6 hours, or both, induces diuresis and may reverse acute
tion. Another group of patients who briefly have unrestricted renal failure associated with CPB. Some centers recommend
pulmonary blood flow preoperatively may end up with arterial placement of peritoneal dialysis catheters at the end of surgery
media hypertrophy, which might result in pulmonary hyper- in high-risk infants for a better outcome.6 Furthermore, the use
tension. This clinical picture can complicate the termination of of MUF is effective in reducing total body water and limiting
bypass and may result in failure to wean from CPB and acute the undesired effects of CPB.27,28
Cardiopulmonary Bypass in Infants
Asli Dönmez, MD,* and Okan Yurdakök, MD†
T HE INCIDENCE OF congenital heart defects is approx-
imately 7 to 10 per 1,000 live births.1 With advancing
technology and improved diagnostic, surgical, anesthetic, and
and jeopardize systemic perfusion. In addition, development of
collateral vessels secondary to cyanosis and vascular obstruc-
tion may result in significant blood loss and impair surgical
postoperative management protocols, the tendency today is to field exposure.
perform the complete repair of defects early in infancy.1 Infants are characterized by a high metabolic rate and, thus,
Infancy is defined as the period from birth until age 1. The oxygen demand requiring higher flow rates per body surface
management of cardiopulmonary bypass (CPB) in infancy has area. Because they have limited cardiac and respiratory
many challenges and increased risk of morbidity and mortality reserves, in physiologically stressful circumstances rapid
compared with that of the adult population. Infants are more changes of pH, lactic acid, glucose levels, and temperature
prone to complications because of the immaturity of their organ may occur because of a compromised response to meet these
systems. There is a need for a more complete understanding of demands.
the anatomic, metabolic, and physiologic differences between Infants are prone to hypothermia because of their larger ratio
infants and adults, and patient care must be individualized of body surface area to weight and limited fat stores and have
considering the degree of hemodilution and hypothermia, acid- limited ability to deal with cold stress, which result in increased
base strategies, flow rates, circuit designs, priming the pump, oxygen consumption and may cause metabolic acidosis.7
and choice of cannulae.2 Neonatal myocardium is known for its immaturity compared
This review article outlines the differences between infants with the adult myocardium but is considerably more resistant to
and adults regarding their responses to CPB and reviews the ischemia. In the newborn, only 30% of the myocardial mass
main subjects like hypothermia, hemodilution, acid-base strat- acts as contractile tissue, compared with 60% of mature
egies, inflammatory response, extracorporeal circuit, and CPB myocardium. In addition, pediatric myocardium has fewer
protocols for infants. mitochondria, less oxidative capacity, and incomplete auto-
Since the first successful application of extracorporeal nomic innervations. Because the sympathetic innervations are
circulation in the 1950s,3 CPB has evolved and still is also immature, the control of vascular tone and myocardial
evolving, but basic concepts have remained the same: Oxy- contractility depends on adrenal function via catecholamines
genation and carbon dioxide elimination, perfusion, systemic rather than direct autonomic influences.8,9
cooling and rewarming, and removal of blood from the heart to As is well documented, the infant myocardium relies
provide a blood-free surgical field.4 On the other hand, despite heavily on glucose as its major substrate and also has a greater
clear understanding of the basic concepts and many improve- reliance on extracellular calcium for calcium-mediated excita-
ments, CPB management in infants still remains challenging tion coupling.10,11
and unique. The immature myocardium uses glucose as the main
substrate and also has an increased ability to utilize anaerobic
DIFFERENCES BETWEEN INFANTS AND ADULTS metabolism as well as an ability to metabolize fatty acids,
There are major differences between infants and adults ketones, and amino acids. Interestingly, 90% of ATP produc-
affecting their response to CPB (Table 1).5 Procedures per- tion in the mature heart is by the oxidation of the long chain
formed on infants and children may require the extreme fatty acids12 and not by utilization of glucose.
measures that are not necessary for adults, including deep The immature myocardium is a great deal more sensitive to
hypothermia, hemodilution, different acid-base strategies, low extracellular calcium levels than the mature myocardium. In
perfusion pressures, and wide variation of perfusion flow rates.
These measures notably vary from those of normal physiology
and affect protection of normal organ function during CPB. In From the *Department of Anesthesiology, Mugla University School
addition, their smaller circulating blood volume, higher oxygen of Medicine and the †Department of Cardiovascular Surgery, Turkey
consumption rate, reactive pulmonary vascular bed, immature Yuksek Ihtisas Hospital, Ankara, Turkey.
Address reprint requests to Asli Dönmez, Guniz Sokak, 23/19,
organ systems, and altered thermoregulation may cause vulner-
Kavaklidere, Cankaya, 06700, Ankara, Turkey. E-mail: aslidonmez
ability to deleterious effects of CPB in infants.6
@hotmail.com
The presence of large aorta-pulmonary collateral vessels or © 2014 Elsevier Inc. All rights reserved.
an interrupted aortic arch also necessitate changes in CPB 1053-0770/2601-0001$36.00/0
strategies and cannulation techniques. The cardiac pathology http://dx.doi.org/10.1053/j.jvca.2013.12.024
with large intra- and extracardiac shunts may result in a greater Key words: CPB, infants, hypothermia, hemodilution, acid base
redistribution of flow away from the vital organs during CPB strategies, inflammatory response, extracorporeal circuit
Journal of Cardiothoracic and Vascular Anesthesia, Vol ], No ] (Month), ]]]]: pp ]]]–]]] 1
, 2 DÖNMEZ AND YURDAKÖK
Table 1. Comparison of Adult and Pediatric CPB
Parameter Adult Pediatric
Minimum CPB temperature Rarely o251-321C Frequently 151-251C
Use of total circulatory arrest Rare Common
Pump prime
Dilution of blood volume 25%-33% 150%-300%
Whole blood or RBC added Rare Frequent
Perfusion pressure 50-80 mmHg 20-50 mmHg
Acid-base management strategy Alpha-stat pH-stat at temperature o281-301C
Glucose management
Hyperglycemia Frequent, requires insulin Less common
Hypoglycemia Rare Common, reduced hepatic glycogen stores
NOTE. Modified from DiNardo and Zvara.5
Abbreviations: CPB, cardiopulmonary bypass; RBC, red blood cells.
mature hearts, most of the calcium required for myocardial right-sided heart failure and may require extracorporeal sup-
contraction is provided by the sarcoplasmic reticulum, whereas port. Liquid ventilation, steroid use, and modified ultrafiltration
the sarcoplasmic reticulum is underdeveloped in the immature (MUF) seem to improve pulmonary function.6,7 MUF is highly
heart and has reduced storage capacity for calcium.13,14 The effective in reducing lung water and pulmonary morbidity.
activity of the sarcoplasmic calcium ATPase, the enzyme There are studies reporting that both the degree of hemodilution
responsible for calcium reuptake into the sarcoplasmic retic- and increased flow rates during CPB may cause worsening of
ulum, also is reduced relative to mature myocardium. There- lung injury.19,20
fore, the immature heart has lower intracellular calcium Renal dysfunction after CPB is another important cause of
concentration with a greater dependence on extracellular morbidity and mortality. The incidence of acute renal failure
calcium levels and is much more sensitive to calcium channel (ARF) varies between 0.7% to 59% depending on the complex-
blockers than the mature heart. Use of cardioplegic solutions ity of the surgical procedure.21–24 In the pediatric population,
containing normal or high calcium concentrations may have kidney function does not reach to adult level until the age of 2.7
detrimental effects, and use of solutions containing subphysio- Glomerular filtration rate is lower in neonates and infants
logic levels of calcium is recommended.15 Boston Children’s because of lower mean arterial pressure and high renovascular
Hospital’s experience shows that it is an advantage to have resistance. This results in impaired concentrating and diluting
very low levels of ionized calcium during the cooling phase mechanisms, sodium reabsorption and excretion, and acid-base
before aortic cross-clamping. There may be advantages in regulation. Use of CPB in infants is associated with higher fluid
having a lower ionized calcium level during hypothermic accumulation than adults, resulting in an increase in body water.
bypass as well. Therefore, calcium is not recommended to be The combined effects of hypothermia, nonpulsatile perfusion,
corrected until the later phase of rewarming.16 and lower mean arterial pressures may cause release of hormones
Immaturity also affects a number of enzymatic processes, like vasopressin, renin, angiotensin, and catecholamines, which
some examples of which are decreased antioxidant enzymatic leads to renal vasoconstriction and reduced renal blood flow
activity, causing the immature myocardium to be more resulting in oliguria and elevated serum creatinine levels.
susceptible to anaerobic metabolism, and decreased 5- Blinder et al25 retrospectively studied 430 infants (o90
nucleotidase activity, causing conversion of ATP to adenosine days old) who underwent congenital heart surgery. They used a
to decrease. In fact, the latter may explain why immature modified pediatric version of the Acute Kidney Injury Network
myocardium is more tolerant to ischemia.17 classification and found that postoperative acute kidney injury
Pulmonary dysfunction is common after CPB because lungs occurred in 52% of the infants: 31%, 14%, and 7% of infants
are still immature at birth and continue to grow and mature up reached acute kidney injury stage I, II, and III, respectively.
to 8 years of age. Lungs have 2 components, parenchymal and Single-ventricle status, CPB, and higher reference serum
vascular, and both of them serve as a source and target of the creatinine levels were associated with postoperative acute
inflammatory response during CPB.18 Both systemic inflam- kidney injury.25
matory response and ischemia/reperfusion injury during CPB Recently, significant interest has arisen regarding prevention
stimulate endothelial injury, resulting in capillary leak and of fluid accumulation and its possible positive influence on
extravasation of the fluid and the inflammatory cells to the mortality.26 The management of infants undergoing CPB is
parenchymal space and pulmonary edema, ending with poor focused on a negative total body water balance and, therefore,
oxygenation, reduced compliance, and reduced lung volumes. loop diuretics commonly are used to increase urine output.9
Patients with increased pulmonary blood flow may need intense Furosemide (1-2 mg/kg) or ethacrynic acid (1 mg/kg) every 4
medical therapy preoperatively to reduce pulmonary conges- to 6 hours, or both, induces diuresis and may reverse acute
tion. Another group of patients who briefly have unrestricted renal failure associated with CPB. Some centers recommend
pulmonary blood flow preoperatively may end up with arterial placement of peritoneal dialysis catheters at the end of surgery
media hypertrophy, which might result in pulmonary hyper- in high-risk infants for a better outcome.6 Furthermore, the use
tension. This clinical picture can complicate the termination of of MUF is effective in reducing total body water and limiting
bypass and may result in failure to wean from CPB and acute the undesired effects of CPB.27,28
