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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.55 no.1 Campinas Jan./Feb. 2005
Anesthesia for the newborn submitted to cardiac surgery with cardiopulmonary bypass*
Anestesia para el recién nacido sometido a cirugía cardiaca con circulación extracorpórea
Sérgio Bernardo Tenório, TSA, M.D.I; Débora O Cumino, TSA, M.D.II; Daniela B G Gomes, TSA, M.D.II
IProfessor Adjunto da Faculdade de
Medicina da Universidade Federal do Paraná; Co-Responsável pela Residência
em Anestesiologia do CET/Hospital Cajuru de Curitiba; Responsável pelo
Programa de Especialização em Anestesia Pediátrica do Hospital
Infantil Pequeno Príncipe - Curitiba, PR
IIAnestesiologista do Hospital Infantil Pequeno Príncipe; Co-Responsáveis pela Residência em Anestesiologia do CET/ Hospital Cajuru de Curitiba, PR
BACKGROUND AND OBJECTIVES: Congenital
heart diseases affect 0.8% of liveborn infants and many need neonatal surgical
correction. Cardiac surgery with cardiopulmonary bypass (CPB) in this age is
associated to higher risk of complications related to child's functional
immaturity, lack of CPB equipment fully compatible with neonate (NN) size and
technical difficulties to correct cardiac defects. This article aimed at describing
aspects related to anesthetic technique, CPB and their effects on NN.
CONTENTS: High fentanyl or sufentanil doses promote adequate anesthesia without interfering with cardiocirculatory stability. Opioids residual respiratory depression is not a problem for these patients because most of them will need immediate postoperative respiratory assistance. CPB may be followed by heart manipulation-induced hypotension and/or bleeding. Inadequate venous and aortic cannula position may lead to severe complications, such as insufficient brain flow or difficult venous drainage. Deep hypothermia and total circulatory arrest are common during CPB. Hypothermia changes blood viscosity, which is treated with hemodilution and has implications on pH correction (alpha-stat versus pH stat). Low cardiac output is common during CPB weaning and adjustments in one or all its components (preload, contractility, afterload and heart rate) may be necessary. In addition to classic drugs, such as epinephrine and dopamine, other substances may be needed, such as aprotinin, nitric oxide or phosphodiesterase inhibitors.
CONCLUSIONS: Anesthesiologists play a major role in adjusting perioperative homeostasis. Understanding the type of cardiac disease, the correction to be performed and body response to CPB may be useful for the management of those children.
Key words: SURGERY, Cardiac: pediatric, cardiopulmonary bypass
JUSTIFICATIVA Y OBJETIVOS: Las enfermedades
congénitas del corazón alcanzan 0,8% de los recién nacidos (RN)
vivos, siendo que muchos necesitan corrección quirúrgica aún
en el período neonatal. La cirugía cardiaca con circulación extracorpórea
(CEC), en esta faja de edad, se asocia la mayor incidencia de complicaciones,
debido a la inmadurez funcional del niño, a la falta de equipos de CEC
que sean totalmente compatibles con las dimensiones del RN y a las dificultades
técnicas para corrección de la lesión cardiaca. Este artículo
tiene el propósito de presentar los aspectos relacionados a la técnica
anestésica, la CEC y sus efectos en RN.
CONTENIDO: Elevadas dosis de fentanil o sufentanil abastecen de adecuada anestesia sin interferir en la estabilidad cardiocirculatoria. La depresión respiratoria residual de los opioides no es problema en este grupo de pacientes porque la mayoría necesita asistencia respiratoria en el post-operatorio inmediato. La entrada en CEC puede ser acompañada de hipotensión arterial por manipulación del corazón y/o sangramiento. El posicionamiento inadecuado de las cánulas venosas y aórtica pueden causar serias complicaciones, como insuficiente flujo encefálico o dificultad en el drenaje venoso. Son comunes la utilización de hipotermia profunda y la parada circulatoria total durante la CEC. La hipotermia modifica la viscosidad de la sangre que es tratada con hemodiluición y trae implicaciones para la corrección del pH (alfa-stat x pH stat). En el desmame de la CEC es frecuente ocurrir bajo debito cardíaco y ajustes en uno o en todos sus componentes (pre-carga, contratilidad, post-carga y frecuencia cardiaca) pueden ser necesarios. Además de las drogas clásicas, como la adrenalina y la dopamina, puede ser necesario el empleo de otras substancias como la aprotinina, el óxido nítrico o los inhibidores de la fosfodiesterasa.
CONCLUSIONES: El anestesista tiene papel preponderante en el ajuste de la homeostasia durante el período peri-operatorio. Conocimientos sobre el tipo de lesión cardiaca, la corrección a ser realizada, la respuesta del organismo a la CEC pueden ser útiles en el manoseo de estos niños.
Congenital cardiopathies affect approximately 0.8% of liveborn infants. The severity of these diseases varies from simple atrial septum defects which may be corrected at school age or even later, to very severe injuries demanding neonatal surgery (Chart I). Perioperative care of children submitted to cardiac surgery with cardiopulmonary bypass (CPB) varies with age and neonates (NN) are more susceptible to complications.
CARDIOPULMONARY BYPASS PERIOD
Several NN arrive at the operating center under prostaglandin and inotropic infusion. These drugs should be maintained until beginning of CPB. Prostaglandin allows for survival when pulmonary or systemic flow depends on arterial canal patency and should be maintained until perfusion, even at risk of promoting hypotension, apnea and other complications 1.
Robinson and Gregory 2 were the first to show that high fentanyl doses would promote anesthesia without interfering with hemodynamic balance of cardiac NN. Further studies have confirmed such findings electing fentanyl in doses varying 30 to 100 µg.kg-1, or sufentanil in doses varying 5 to 20 µg.kg-1 3-10, as the technique of choice for children with poor cardiac reserve 3-10. However, even with these high opioid doses, some patients present increased intraoperative blood pressure, probably due to inadequate endocrine-metabolic response blockade 11.
In general, low concentrations of volatile agents, such as isoflurane, or low benzodiazepine doses are enough to control blood pressure. Pancuronium's vagolytic action makes it the neuromuscular blocker of choice to be associated to low opioid doses to prevent bradycardia. These drugs should be injected simultaneously to prevent chest stiffness, which is common after high opioid doses. Other non-depolarizing neuromuscular blockers may be used if care is taken to previously administer a parasympatholytic agent.
Remifentanil is a new synthetic plasma-metabolized opioid with fast onset and excretion. One of few studies on this drug in children submitted to cardiac surgery has shown that there is adequate endocrine-metabolic response blockade and hemodynamic stability with 1 µg.kg-1.min-1 12. However, NN and infants present major blood pressure and heart rate decrease with this dose suggesting the need for further studies of this drug for this population.
Intravenous fentanyl or sufentanil associated to pancuronium seldom promotes hemodynamic changes. However, several NN arrive at the operating center without a venous catheter and, in these conditions, several venous puncture attempts may promote severe hemodynamic response with increased pulmonary and systemic vascular resistance. Inhalational anesthesia could be the best alternative for these cases, although myocardial depression and hypotension may be present with any inhalational anesthetic in equipotent doses 13-16.
The severity of cardiovascular hemodynamic changes is concentration-dependent and, barring exceptions, most NN tolerate inhalational induction with low volatile anesthetic concentrations. Sevoflurane is progressively replacing halothane in pediatric anesthesia for its low solubility, less pungent odor and higher cardiocirculatory stability. A study with 180 children submitted to congenital cardiopathy correction has shown a lower incidence of hypotension with sevoflurane as compared to halothane. However, the incidence of hypotension was higher in NN and infants with both drugs 17.
FiO2 and Pulmonary Ventilation
It is in general recommended children with cardiac disease should be modestly hyperventilated and receive high O2 concentrations. This ventilation regimen is useful for most cyanotic children because it decreases pulmonary vascular resistance and improves pulmonary flow. However, NN with some congenital cardiopathies, such as truncus arteriosus and hypoplastic left ventricle syndrome (HLVS), although cyanotic, do not tolerate pulmonary vascular resistance decrease promoted by hyperoxia and hypocarbia. In most common truncus arteriosus presentations, both pulmonary artery branches emerge from a single vessel, called truncal vessel, and there is major ventricular septum defect (Figure 1).
Pulmonary and systemic circulations are in parallel in a way that decreased pulmonary vascular resistance (PVR) will increase blood flow shifted to pulmonary circulation, causing increased left ventricle blood volume and end diastolic pressure. Systemic flow shift to pulmonary circulation also promotes diastolic pressure decrease of the truncal vessel, from which coronary arteries emerge. The association of high left ventricle end diastolic pressure and low truncal vessel diastolic pressure decreases coronary perfusion, promoting a precarious balance between myocardial oxygen supply and demand, causing myocardial ischemia and death 18.
In hypoplastic left ventricle syndrome (HLVS) children, left ventricle and aortic arch are hypoplastic (Figure 2). The only functioning ventricle supplies both circulations: pulmonary via pulmonary artery, and systemic via ductus arteriosus. Any PVR decrease will increase pulmonary flow at the expenses of systemic circulation, promoting severe metabolic acidosis and death. Truncus arteriosus and HLVS neonates benefit from high pulmonary pressure obtained with low PaO2 and high PaCO2. These conditions are in general obtained with 0.21 FiO2 (adding oxygen if SpO2 is below 80%), respiratory and tidal volume decrease. A mixture of 5% CO2 may be added to inspiratory flow to reach PaCO2 equal to or above 45 mmHg 19.
CARDIOPULMONARY BYPASS (CPB)
Although being a seemingly safe procedure, CPB is a poorly physiologic method responsible for several postoperative complications of cardiac surgeries 20. During perfusion, NN are exposed to physiologic extremes which are seldom needed for adults. For example, while aortic flow during adult perfusion is maintained in approximately 50 mL.kg-1.min-1, in NN it may vary from 200 mL.kg-1.min-1 in beginning and end of perfusion until total circulation arrest. Another major difference between adults and NN is temperature, which is maintained close to physiologic values for adults and in deep hypothermia for NN; hypothermia has major physiologic effects on pH, blood viscosity and fluid capillary filtration.
CPB circuit volume (tubes, oxygenators, filters) is proportionally higher in NN equipment resulting in at least two consequences: a) higher perfusate volume to fill the system generating further dilution of red cells, coagulation factors and proteins and requiring higher homologous blood volumes (homologous blood is seldom used in adults); b) higher NN blood exposure to non-endothelial surfaces inducing more severe inflammatory response.
Hypotension is common during aortic and venae cavae catheterization and is in general due to bleeding or heart manipulation. If hypotension period is short and perfusion is imminent there is no need for intervention because circulation will soon be transferred to CPB. If there is persistent hypotension and aorta is already catheterized, enough perfusate volume may be infused by the aortic cannula to normalize blood pressure. But this approach may promote arrhythmia, bradycardia, heart distension and cardiac arrest because perfusion temperature is low. When hypotension is due to heart manipulation and it is impossible to interrupt the maneuver, single phenilephrine (1 to 5 µg.kg-1.min-1) or other vasopressor dose may be useful.
Severe complications may come from inadequate aortic or venae cavae cannulas position. Brain flow may be compromised if distal aortic cannula tip is above the brachiocephalic trunk. Inferior vena cava cannula may enter false pathways, such as hemiazygos or hepatic vein and impair blood drainage to the oxygenator. Venous drainage obstruction is identified by decreased volume returning to CPB circuit, face edema, abdominal distension and gradual loss of blood reservoir level. Ascites and renal, gastrointestinal and liver failure may be observed in the postoperative period 21.
Anesthesia during CPB
Soon after CPB, blood anesthetic concentration (opioids, benzodiazepines, volatile anesthetics and neuromuscular blockers) is dramatically decreased by increased drugs distribution volume, now made up of NN volume (around 250 mL) plus perfusate volume (between 400 and 700 mL, depending on the oxygenator). Some anesthetics, such as fentanyl and isoflurane, adhere to oxygenators silicone membranes thus contributing to decrease their blood concentration22. Although deep hypothermia leads to pain insensitivity, anesthetic perfusates and neuromuscular blockers should be added to perfusate to promote anesthesia during normothermia or moderate hypothermia periods. An isoflurane vaporizer could be installed in the oxygen line connected to the oxygenator. Isoflurane promotes anesthesia and helps blood cooling and warming during perfusion due to its vasodilating action. Decrease in blood temperature increases volatile anesthetics solubility and prolongs excretion time 23, but a study has shown that up to 95% isoflurane is excreted 6 minutes after its withdrawal 24.
Anticoagulation and its Reversion
Heparin is used to block coagulation cascade during CPB. It amplifies in up to 10 thousand times endogenous anticoagulant antithrombin (AT) potency. AT levels are much lower in NN who, then, have some degree of heparin resistance 25. Although initial heparin doses (in mg.kg-1) are identical for adults and children (3 to 4 mg.kg-1), total perfusion dose is higher for NN since blood added to perfusate (mean of 300 mL) receives heparin in the ratio 5 mg:100 mL. This excess heparin may be the cause for more severe bleeding in children after CPB weaning.
Response to heparin varies among individuals and its effect on coagulation should be frequently monitored. Circulating serum heparin dosage during perfusion is a time-consuming test thus inadequate to control heparinization during perfusion. Activated coagulation time (ACT) is a fast and simple method to evaluate coagulation and may be operated by the professional in charge of perfusion. However, correlation between ACT and blood heparin levels in children is low, probably due to pediatric perfusion characteristics, such as higher hemodilution, homologous blood utilization, fibrinolysis, thrombocytopenia, platelet activation, hypothermia and coagulation factors deficiency. But this poor correlation with heparin blood levels does not lower the importance of ACT because, in practical terms, knowing blood coagulation status is more important than knowing heparin blood level 27.
Protamin dose needed to neutralize heparin is proportionally higher in NN as compared to older children and adults 28. Although children seem to be protected against protamin-triggered anaphylactic and anaphylactoid reactions, data in the literature suggest the inexistence of substantial differences in the incidence of hemodynamic complications. From 1249 children of different ages, from NN to adolescents, 1.76% have presented hypotension after protamin injection, similar to adult patients 29. Although seemingly uncommon, severe complications induced by anaphylactic reactions may occur, as suggested by a case report of an infant with 6 weeks of age who presented, immediately after protamin injection, sudden pulmonary pressure increase, bronchospasm, pulmonary edema, decreased pulmonary compliance and hypotension 30. Although current perception being that coagulation management and monitoring during perfusion are not ideal, there are no better alternatives so far 26.
Blood Flow During Perfusion: Low Flow and Total Circulatory Arrest (TCA)
During perfusion in normothermia or moderate hypothermia, flow injected through the aortic cannula varies from 50 mL.kg-1.min-1 in adults to 150 to 200 mL.kg-1.min-1 in NN. Up to 30% of injected aortic flow may be shifted by systemic-pulmonary collaterals 32. This blood shifted from the aorta to pulmonary veins may impair brain irrigation and, by flooding the heart, may impair identification and correction of cardiac defects 33. Decreased aortic flow to 30 to 50 mL.kg-1.min-1 decreases collateral vessels flow and promotes a "cleaner" surgical field. To help correction of complex NN heart defects, aortic and cavae cannulas are frequently removed and circulation is arrested for up to 60 minutes. Total circulatory arrest or low flow are only possible with simultaneous deep hypothermia.
Deep hypothermia is the most effective means to maintain live cells in the absence of oxygen, because it preserves high energy intracellular phosphates, decreases glutamate and other excitatory neurotransmitters release, maintains cell membranes patency and decreases calcium entrance in cells 34. At 18 ºC, cell metabolism is decreased to 10% of normothermal baseline values 35. Hypothermia efficacy in brain protection depends on some cares, such as: homogeneous cooling obtained by slow temperature decrease and ice around the head 36. It is also recommended that warming at perfusion completion be slow, in a rate not higher than 1 ºC per minute, preventing hyperthermia which may worsen neurological injury after total circulatory arrest 37.
Early studies have suggested that under deep hypothermia (< 20 ºC), a child could remain in total circulatory arrest (TCA) for up to 60 minutes without neurological injury. More accurate neurological studies during late postoperative period, however, have shown than many children presented signs of brain ischemia after shorter TCA periods 38. Since in general it is not possible to correct congenital heart disease in less than 60 minutes of TCA, other brain protection measures are being investigated.
In parallel to hypothermia protecting effects, its use brings some inconveniences. For example, cooling increases blood viscosity and requires hemodilution which causes edema for helping capillary fluid leakage to the interstitium, condition which modifies heart, lungs and CNS function 39. Barbiturates have been used for brain protection due to their antioxidant and anticonvulsivant activity, in addition to decreasing cell oxygen consumption. A study, however, has shown that barbiturates have decreased intracellular high-energy phosphates content in patients submitted to hypothermia. Since intracellular concentration of high-energy phosphates plays important role in ischemic cell protection 40, many centers have abandoned the use of barbiturates during CPB aiming at brain protection 41.
Acid-Base Balance Regulation during Hypothermia
Fluid temperature decrease changes its pH and gases partial pressure. This phenomenon is known since early 20th century but has only raised clinical interest after the introduction of deep hypothermia during CPB. Temperatures of 15 ºC or even lower are not uncommon during CPB in NN and infants and in this temperature extreme, pH, PCO2 and PaO2 values are very different from normothermal values (Table I). For example, blood cooling from 37 ºC to 20 ºC will change pH and PaCO2 from 7.4 and 40 mmHg to 7.65 and 19 mmHg, respectively, only by effect of temperature. This occurs because temperature decrease changes water dissociation constant decreasing the amount of H+ ions released in the medium, and increases gases solubility thus decreasing their partial pressure (Table I).
It is known that, in normothermia, cell function depends on blood pH maintenance in approximately 7.4, however optimum pH for deep hypothermia is unknown. There are two theories to correct pH in hypothermal patients, based on opposed strategies, called pH stat and alpha-stat. pH stat strategy considers that ideal blood pH should be 7.4 regardless of patient's temperature. This strategy demands blood temperature at collection to be known and a normogram to obtain actual pH. Since pH is increased and PCO2 is decreased during hypothermia (Table I) it is necessary to add CO2 to the oxygenator to correct pH to 7.4. Advocates of the pH stat method argue that CO2 added to the oxygenator, in addition to normalizing pH, has other two beneficial effects on hypothermal children: increases brain flow allowing for more homogeneous cooling, and shifts hemoglobin dissociation curve to the right, making easier hemoglobin-bound oxygen release to tissues. These two effects are, at least in theory, desirable since hypothermia promotes vasoconstriction which could impair the cooling of some brain areas, and shifts hemoglobin dissociation curve to the left impairing oxygen release to cells.
Alpha-stat strategy works with the hypothesis that ideal pH varies with temperature. For example, ideal pH for blood at 20 ºC would be 7.65, rather than 7.4 (Table I). To adopt alpha stat strategy it is not necessary to measure actual blood temperature because any device measuring pH and gases will warm blood sample to 37 ºC. Advocates of alpha stat strategy suggest that it is more adequate for cellular function because temperature decrease increases pH but maintains H/OH ratio unchanged. For several physiologists, H/HO ratio maintenance is more important for cellular function than absolute pH value. A criticism to the pH stat method is that CO2 migrating to the cell promotes intracellular acidosis and H/HO ratio unbalance 43.
pH stat versus alpha-stat: Which is the best way to Correct pH?
Although the adoption of both strategies implies antagonistic approaches (add or not CO2 to the oxygenator), so far there are no experimental or clinical studies showing the superiority of one over the other. Even among different animal species with physiologic hypothermia there are differences in pH control mechanisms. For example, hibernating animals when in hypothermia, maintain stable pH in approximately 7.4 at the expenses of CO2 retention (pH stat); on the other hand, poikilothermal animals change their pH with cooling (alpha- stat) 44. pH stat method seems to promote better brain protection in short term observations, however, late evaluations were unable to confirm such findings.
A study with 182 infants submitted to deep hypothermia and TCA has shown that the pH stat strategy group had lower incidence of morbidity, shorter ECG activity recovery time, faster recovery and, in subgroups with specific heart defects, shorter ventilatory assistance and ICU stay45, while a different study has not detected differences in neurobehavioral evaluation of children managed by both strategies 46. A behavioral and histological study with piglets submitted to deep hypothermia and total circulatory arrest for 90 minutes has suggested central nervous system benefits with pH stat strategy 47. Care must be taken, however, with the interpretation of animal experiment results.
POST-CARDIOPULMONARY BYPASS PERIOD
After cardiac defect correction with total circulatory arrest, all cannulas are reintroduced in aorta and right atrium or venae cavae and perfusion is restarted with blood warming. When temperature is normalized, most of the times the heart returns to spontaneous beating and CPB weaning is started with interruption of venous cannulas flow but maintaining aorta cannula for some minutes for blood volume replacement. Lungs, which have remained collapsed during perfusion, are mechanically ventilated after being manually expanded with higher tidal volume. After this, there is major cardiopulmonary instability due to CPB and surgery effects on homeostasis.
Excessive bleeding is common in NN after CPB. Several contributing factors are: coagulation elements immaturity, excessive circulating heparin, low AT levels and coagulation factors dilution 48,49. Red cells and coagulation factors replacement may be achieved with red cells concentrate plus fresh frozen plasma or fresh whole blood. At least one study has shown that NN and infants submitted to CPB have shown less bleeding when receiving fresh whole blood after perfusion. Presumable mechanism would be better platelet function preservation 50. It seems that this study has not been questioned and many centers try to use fresh blood for NN perfusion whenever possible.
Pulmonary Function Post-CPB
CPB affects several organs but lung and heart changes are those with immediate repercussions. Respiratory function after CPB 51 is changed in most patients, but in NN these changes are more severe. Major CPB-induced pulmonary change is pulmonary edema. After perfusion, children present decreased lung dynamic and static compliance, decreased functional residual capacity, increased alveolar-arterial gradient, increased airway closing volume and diffuse atelectasis, all caused by pulmonary interstitium and alveoli infiltration. After perfusion, there might be abundant secretion obstructing bronchi and bronchioli and making pulmonary deflation difficult. This secretion may be bloody in NN with lots of systemic-pulmonary collateral circulation.
Hemodilution, hypothermia and action of products released by inflammatory cascade activation are causes of post-CPB pulmonary edema. Hemodilution, needed to decrease blood viscosity during hypothermia, decreases oncotic plasma pressure and helps capillary fluid leakage to interstitium. Hypothermia also seems to be independent of hemodilution effects, which are a cause of tissue edema 39.
CPB promotes severe inflammatory response in adults and children with major clinical implications for several organs 52. There are many CPB-related factors able to trigger inflammatory response, such blood exposure to non-endothelial surfaces of CPB circuits, deep hypothermia, TCA, ischemia-reperfusion phenomena, hemodilution and stress generated by constant flow on vessel walls.
Most peripheral inflammation markers are increased during and after CPB, as cytokines, TNF, IL 6 e IL8, elastases and myeloperoxidases, and complement activation products. These substances released in the blood cause cell injury with dysfunction in several organs. Alveolar-capillary membranes and capillary endothelium are targets for pro-inflammatory cytokines and complement system activation products 53. Endothelial dysfunction is part of exaggerated systemic inflammatory response and is manifested as interstitial edema by endothelial barrier function change; it produces substances which control vascular tone, such as nitric oxide (NO) endothelin and prostacyclin 55. Pulmonary hypertension is frequently observed in neonates with arteriolar mid layer hypertrophy, as with patients with pulmonary hyperflow and abnormal pulmonary veins drainage.
Heart is among most affected organs by CPB, and low cardiac output syndrome affects 30% to 50% of children in the postoperative period 56. In addition to not receiving blood flow throughout CPB, heart is perfused with cardioplegic solution which, in general, has low temperatures. Surgery-related factors may also lead to low cardiac output. For example, atrial cannulas may aggress sinusal node and cause arrhythmias; edema, as well as conduction bundles manipulation, may lead to conduction blockade; cardiac muscle resection used to correct tetralogy of Fallot's right ventricle obstruction causes cardiac dysfunction. Cyanosis and heart failure may decrease the number of heart beta-adrenergic receptors. Low perfusate and cardioplegia temperatures cause the decoupling of beta-adrenergic receptors and adenylcyclase. This uncoupling prevents beta receptors from activating adenylcyclase. As result of decreased cAMP, there is decrease in calcium supply to muscle fibers and contractile function impairment 13
Low Cardiac Output Management
Post-perfusion period in small children without adequate circulatory monitoring is difficult to manage. In addition to invasive blood pressure, right ventricle filling pressure (central venous pressure) or left ventricle filling pressure (left atrium pressure) have to be evaluated depending on the type of cardiac defect. Catheters are placed by the surgeon at perfusion completion under direct view.
The decision on which filling pressure to use depends on type of defect and ventricular aspect. For example, in tetralogy of Fallot patients, central venous pressure (CVP) is more useful due to the higher probability of right ventricle dysfunction; in patients with major arteries transposition submitted to Jatene's surgery, it may be more important to monitor left atrium pressure (LAP) since left ventricle is more requested because after surgical correction it has to eject into systemic circulation (in major arteries transposition, pulmonary artery emerges from left ventricle); in children with annomalous pulmonary venous connection, in addition to LAP measurement, it may be also necessary to measure pulmonary artery pressure due to frequent postoperative pulmonary hypertension episodes.
Extreme care should be taken to prevent air entrance in radial artery and left atrium catheters, by using systems allowing continuous infusion of low fluid volumes with heparin, such as intraflow systems which infuse approximately 3 mL.hour-1. In the absence of such systems, infusion pumps may be used and intermittent heparinized solution injection should be avoided because, in addition to the risk of administering excessive fluid and heparin volumes, they allow the entrance of air in the arterial or left atrium catheter. After perfusion, NN frequently present low cardiac output. In this phase, bradycardia is hardly reverted with atropine or other parasympatholytic drug. Best therapy to increase HR after perfusion is atrio-ventricular pacemaker. On the other hand, ejection volume results from the interaction of three factors: preload, contractility and afterload (EV - preload x contractility x afterload). Intervening in two or all factors may be necessary to normalize cardiac output.
Preload may be defined as the ratio between blood volume and heart ability to eject it and is evaluated by filling pressures measurement. CVP measures right ventricle preload and LAP left ventricle preload. One has to bear in mind that true preload evaluation is given by ventricles end diastolic volume measurement, but for technical reasons (it is difficult to measure volumes), mean atrial pressures are measured, which are identical to ventricular end diastolic pressures.
So, CVP and LAP only estimate ventricles end diastolic volume. Since the ratio between pressure and volume depends on compliance, compliance changes may change filling pressures. For example, for the same volume, filling pressure will be higher in children with higher ventricular hypertrophy due to lower ventricular compliance. Due to low compliance and ability to compensate volume changes, any NN blood loss will be followed by hypotension and filling pressures decrease; on the other hand, excessive fluid replacement may easily promote heart distension, cardiac failure and arrest. So, it is important to carefully titrate blood and other colloids or crystalloids replacement. Blood is more adequately replaced with the help of a syringe and intermittently infusing 5 mL increments followed by blood pressure and filling pressures responses evaluation (CVP or LAP). Blood pressure maintenance or decrease and fast filling pressure increase indicate that infused volume has gone beyond ventricular ejection ability.
If low output signals persist after volume replacement (low blood pressure, high filling pressure, low diuresis and hypothermia), contractility should be treated by pharmacological means. There are several drugs which can be used alone or in association. Calcium is in general the first choice because NN immature heart has no calcium reserve thus depending on plasma calcium concentration.
Calcium may be replaced with calcium chloride or gluconate in respective intravenous doses of 10 to 20 mg.kg-1 and 50 to 100 mg.kg-1. Calcium chloride should be administered to central vein for being too irritant for peripheral veins. Both should be slowly infused. Dopamine is a natural amine the action of which is dose-dependent. In doses up to 5 µg.kg-1.min-1 it acts on renal arterioles delta receptors; in doses between 5 and 10 mg.kg-1.min-1 its action is predominantly beta-adrenergic, and above 10 µg.kg-1.min-1 alpha-adrenergic only. However, due to high variability in pharmacokinetic and pharmacodynamic response of pediatric patients, higher doses may be needed, especially for neonates, in whom doses of up to 15 µg.kg-1.min-1 are administered.
If low cardiac output persists, epinephrine, which is a natural catecholamine with a and b-adrenergic action, should be used in the doses of 0.05 to 0.5 µg.kg-1.min-1. Beneficial dobutamine effects, well shown in adult patients submitted to cardiac surgeries, have not been reproduced in small children because dobutamine has weak beta-adrenergic action and NN have changes in these receptors. Phosphodiesterase III inhibitors are a category of drugs with different action mechanisms as compared to glucosides and catecholamines. Their action is a consequence of inhibition of phosphodiesterase, enzyme responsible for converting ATP into cyclic AMP.
Increased cAMP optimizes calcium intracellular transportation and improves myocardial contractility. In addition, this category of drugs promotes peripheral vasodilation with lusiotrophic effect, that is, it helps ventricular diastolic relaxation by calcium reuptake after systole. Amnrinone has long excretion half-life (2 to 4 hours) thus is difficult to titrate. Milrinone has the advantage of shorter half-life with lower incidence of thrombocytopenia. In single 75 µg.kg-1 dose followed by 0.75 µg.kg-1.min-1 it prevents low postoperative cardiac output in NN and infants submitted to cardiac surgery with CPB 57.
Left and Right Ventricle Afterload
Left ventricle afterload may be increased as a function of increased systemic vascular resistance by catecholamine release, excessive volume and release of other substances by the body. In some situations, defect correction will impose excessive work to heart, as it may be the case with Jatene's surgery to correct major arteries transposition or pulmonary veins connection. Sodium nitroprusside acts directly on arteries and veins smooth muscles. For having a very short half-life, it is easily titrated, however its metabolites cyanide and thiocianate are toxic. Nitroglycerin is less potent but has no toxic metabolites. Phenoxybenzamine is a pure alpha-adrenergic antagonist, however not available in Brazil.
Many NN present increased pulmonary pressure in the immediate post-perfusion period or later, generating right ventricle afterload increase 58. This is a severe condition calling for immediate intervention and not uncommonly leading to death. In some cases, pulmonary hypertension or its predisposing conditions are already present in the preoperative period, as it is the case with truncus arteriosus, tetralogy of Fallot and annomalous pulmonary venous connection, and diseases characterized, respectively, by high pulmonary flow, low pulmonary flow and pulmonary congestion. In addition to predisposing factors, several other CPB-related factors may promote increased pulmonary vascular resistance, such as microembolysm, leucocytes sequestration in lungs, excess thromboxane, atelectasis, hypoxic pulmonary vasoconstriction and systemic catecholamine release 59. Successful pulmonary hypertension management has always been limited by the lack of drugs acting specifically on pulmonary circulation.
Tolatozine, prostaglandin E1 and prostacyclin, all pulmonary vasodilating drugs, also dilate systemic circulation and hypotension induce by them cancel possible beneficial effects on pulmonary circulation7. The introduction of nitric oxide (NO), endothelium-produced vasodilator, has opened new perspectives for pulmonary hypertension management 54. For being a gas instantaneously metabolized in blood by hemoglobin, it dilates vessels adjacent to alveoli without acting on systemic circulation. However, the same degree of success has not been achieved with NO in all pulmonary hypertension presentations in children with cardiac disease. Best NO results were in patients with pulmonary congestion and excessive amount of smooth muscles in pulmonary venous, as seen in annomalous pulmonary venous connection and congenital mitral stenosis 60-61.
Steroids and Antifibrinolytics
Recent studies have investigated steroids to block inflammatory cascade activation during CPB. Results in the literature with dexamethasone or the association of different steroids differ, with some studies showing decreased inflammatory response however with no change in the incidence of complications 62, while others have shown decrease in inflammation-induced side effects, in addition to decreased inflammatory response 63.
Aprotinin is a nonspecific serum protease which inhibits coagulation, fibrinolysis and complement activation. There is still no consensus on its benefit for pediatric cardiac surgery, although there are favorable results in the literature 64-68. The possible formation of thrombin leading to renal dysfunction and hemodynamic instability is a side effect described with this drug. Epson aminocaproic acid is a synthetic agent inhibiting fibrinolysis by inhibiting plasminogen activation. Studies have shown decreased bleeding with this drug after pediatric cardiac surgery, although no investigation has included only NN 69. Its advantage over aprotinin is lower cost and lower anaphylaxis risk.
Tranexamic acid is 6 to 10 times more potent than epson aminocaproic acid, has half-life of 80 minutes after intravenous administration, inhibits fibrinolysis by blocking plasmin-induced platelet activation and preserves platelet function 66. In summary, these drugs have mechanisms of action which make their use attractive for cardiac surgery, however not all centers use them as routine.
Low Output Refractory to Usual Approaches
In some cases, poor myocardial contractility signs still persist notwithstanding adjusted volume, the use of potent inotropic agents and measures to decrease afterload,. A factor to be investigated is the presence of residual cardiac defect, which can be done with the help of cardiac echocardiography or by evaluating oxygen saturation and pressure in different cardiac cavities, looking for signs of septal defects persistence or gradient between major vessels and their respective cavity.
When low output is caused by residual defect, the only alternative is to restart perfusion and correct it. However, very often there is low output even with adequate correction. In such conditions, a salvaging measure could be the creation of another less severe cardiac defect, such as atrial septum opening. Atrial septum orifice will allow for the flow of excessive blood volume caused by poor ventricular contractility (right in tetralogy of Fallot or left in annomalous pulmonary venous connection) with decreased ventricular end diastolic pressure and filling pressures. Many services also prefer to maintain the sternum open, just closing the skin until cardiac edema regression and cardiac output improvement.
Assisted circulation, option already used for a long time in adult patients with low cardiac output, is being successfully used in pediatric patients, including NN 28. New inotropic drugs with different action mechanisms have been developed. For example, corfolsin, derived from forskolin, is a drug which, as opposed to beta-adrenergic agonists, directly activates adenylcyclase and could be helpful in NN whose beta receptors population is uncoupled from adenylcyclase 70.
Although cardiac correction results in NN have improved in the last decades, morbidity-mortality rate in this group is still higher than in any other age group. Anesthesiologists must understand the pathophysiology of cardiac diseases, the principles of corrective techniques and CPB effects on the body.
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Dr. Sérgio Bernardo Tenório
Address: Rua Dr. Aluízio França, 141 Mercês
ZIP: 80710-410 City: Curitiba, Brazil
Submitted for publication June 8, 2004
Accepted for publication October 19, 2004
* Received from Hospital Infantil Pequeno Príncipe, Curitiba, PR