Pediatric cardiac critical care has made, and continues to make, significant strides in improving outcomes. It is a measure of these successes that much of the discussion in this article does not focus on the reduction of mortality, but rather on perioperative management strategies intended to improve neurologic outcomes. The care of children with critical cardiac disease will continue to rely on broad and collaborative efforts by specialists and primary care practitioners to build on this foundation of success.
Key points
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Prevention of neurologic injury following cardiac surgery or critical cardiac events has become one of the overarching goals of pediatric cardiac critical care.
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Advances in hemodynamic monitoring are allowing early, goal-directed therapy, thereby reducing complications and improving outcomes.
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The evolution of pediatric mechanical circulatory support represents one of the most significant advancements in pediatric critical cardiac disease.
Introduction
Pediatric cardiac intensive care continues to evolve, which is in large part the result of collaborative efforts from anesthesia, surgery, cardiology, critical care, and other subspecialties, including neonatology and neurology. Examples include an increasing number of surgeries in very low birth weight infants; the application of advances in neuroimaging; the extension of technology such as cerebral oximetry from the operating room into the intensive care setting; and innovations in mechanical circulatory devices. Industry-sponsored studies and initiatives from the National Institutes of Health such as the Pediatric Heart Network have contributed to the evolution of pediatric cardiac critical care. These collective efforts are evident in the recently published results of the Berlin EXCOR Ventricular Assist Device trial and the Single Ventricle Reconstruction trial.
The increase in complexity of disease, innovations in technology, and evolving therapeutic strategies, as well as national quality initiatives, individually and collectively place a serious demand on the team, necessitating a focused, concerted effort by all members to challenge current practices while practicing state-of the-art care. Outcomes for pediatric cardiac diseases have improved so much in the past decades that there is now the expectation of perfection and a zero tolerance for complications. Improved mortality is no longer an acceptable goal. This article presents recent advancements in the field that are designed to give improved outcomes that are meaningful, low cost, high value, and reproducible.
Introduction
Pediatric cardiac intensive care continues to evolve, which is in large part the result of collaborative efforts from anesthesia, surgery, cardiology, critical care, and other subspecialties, including neonatology and neurology. Examples include an increasing number of surgeries in very low birth weight infants; the application of advances in neuroimaging; the extension of technology such as cerebral oximetry from the operating room into the intensive care setting; and innovations in mechanical circulatory devices. Industry-sponsored studies and initiatives from the National Institutes of Health such as the Pediatric Heart Network have contributed to the evolution of pediatric cardiac critical care. These collective efforts are evident in the recently published results of the Berlin EXCOR Ventricular Assist Device trial and the Single Ventricle Reconstruction trial.
The increase in complexity of disease, innovations in technology, and evolving therapeutic strategies, as well as national quality initiatives, individually and collectively place a serious demand on the team, necessitating a focused, concerted effort by all members to challenge current practices while practicing state-of the-art care. Outcomes for pediatric cardiac diseases have improved so much in the past decades that there is now the expectation of perfection and a zero tolerance for complications. Improved mortality is no longer an acceptable goal. This article presents recent advancements in the field that are designed to give improved outcomes that are meaningful, low cost, high value, and reproducible.
Neurologic injury and neurodevelopment
Since the first intracardiac repair of congenital heart disease in 1953 (an atrial septal defect by Dr John Gibbon), the mortality in pediatric cardiac surgery has progressively declined, and is currently at less than 3%. With these successes came the appreciation that survivors displayed a high incidence of neurologic, developmental, and psychiatric disabilities. Over the last several years the focus has shifted from efforts directed at improving survival to efforts to improve neurodevelopmental outcomes. Identification of perioperative factors responsible for neurologic injury and impaired neurodevelopment may allow implementation of strategies that will lead to improved outcomes.
With advancements in magnetic resonance imaging (MRI) over the last several years, it has become clear that for some patients abnormal neurodevelopment begins in utero. Limperopoulos and colleagues used three-dimensional volumetric MRI and proton magnetic resonance (MR) spectroscopy to show progressive and significant declines in gestational age-adjusted total brain volume in third-trimester fetuses with some forms of congenital heart disease compared with controls. They also found evidence of impaired neuroaxonal development and metabolism. Abnormal in utero cerebral perfusion impairs cerebral metabolism, and may contribute to impaired neurologic development.
Miller and colleagues used MR spectroscopy and diffusion tensor imaging in newborns with transposition of the great arteries or single-ventricle physiology and found abnormalities of brain metabolism and microstructure before surgery. These alterations were shown in areas of the brain where visible injury on MRI was unappreciated. These abnormalities were widespread and did not conform to the pattern of brain injury that is consistent with hypoxic-ischemic injury of newborns. Syndromic congenital heart disease such as Down, DiGeorge, and Williams include significant neurodevelopmental abnormalities. Additional less well-defined genetic factors may also affect neurodevelopment and recovery from neurologic insults such as ischemia-reperfusion injury.
The advent of noninvasive monitoring of cerebral oxygenation (discussed later) has identified intraoperative and postoperative cerebral hypoxia as an additional factor responsible for neurologic injury and adverse neurodevelopmental outcomes. Kussman and colleagues found perioperative periods of diminished cerebral oxygenation in infants undergoing biventricular repair without aortic arch reconstruction to be associated with significantly lower 1-year psychomotor development index scores and brain MRI abnormalities. Dent and colleagues evaluated brain MRIs before and following the Norwood procedure. Postoperative imaging showed new or worsened ischemic lesions in 73% of patients, which were associated with prolonged low postoperative cerebral oximetry.
Studies have identified the length of stay in the intensive care unit to be strongly associated with adverse neurodevelopmental outcomes, even when adjusting for perioperative events. One factor responsible for this relationship may be the exposure of developing brains to sedatives, analgesics, and anesthetics. Noxious and painful stimuli trigger an immediate neuroendocrine and metabolic stress response that has as an adverse impact in the immediate postoperative period and leads to impaired brain development and abnormalities in behavior. Sedatives and analgesics are provided to minimize the adverse affects of these stimuli; however, the use of these agents is associated with adverse neurodevelopment in newborn animals. Sedatives and analgesics that act through altering synaptic transmission at gamma-aminobutyrate type A (GABA A ) (benzodiazepines, propofol, chloral hydrate) and N-methyl- d -aspartate glutamate (NMDA) (ketamine) receptors may interfere with normal brain development, because GABA-mediated and NMDA-mediated neuronal activity are essential for normal brain development. Several studies in newborn animals have shown widespread neuronal death and impaired neurocognitive function associated with exposure to these agents. Opioids act through different receptors but have also been shown to have a detrimental affect on the developing brain and neurodevelopmental outcomes. The extent to which these findings can be extrapolated to the clinical setting remains to be determined and is currently being evaluated.
Cardiopulmonary bypass–induced inflammation
Cardiopulmonary bypass (CPB) invariably, and to varying degrees, stimulates a systemic inflammatory response that contributes to the development of postoperative organ dysfunction, most notably an increase in vascular permeability, pulmonary edema, and myocardial dysfunction. Kirklin and colleagues were the first to show a positive relationship between complement activation and postoperative morbidity in adults and children undergoing cardiac surgery. The primary stimuli for the inflammatory response are exposure of the blood elements to the nonendothelialized circuit and myocardial and pulmonary reperfusion injury. Numerous studies in animals and humans have investigated the potential role of immune-modulatory strategies for ameliorating the inflammatory response to CPB. Glucocorticoids have been the most extensively studied and are used by most pediatric cardiac centers in the United States and United Kingdom.
There have been several small prospective randomized studies that have evaluated the role of glucocorticoids in suppressing the inflammatory response to CPB. Initial studies showed an improved postoperative course and evidence of reduced myocardial injury in those patients randomized to glucocorticoids before CPB. Two recently conducted prospective randomized dose-response studies evaluated whether an additional dose of glucocorticoids was of any benefit. Patients were randomized to receive a dose of glucocorticoid or placebo 8 hours before the intraoperative dose. Although each study showed a significant reduction in serum inflammatory mediators in patients who received 2 doses of glucocorticoids, neither study showed an improved postoperative course. Checchia and colleagues evaluated a novel strategy for ameliorating the inflammatory response to CPB by delivering gaseous nitric oxide to the membrane oxygenator. Nitric oxide modulates the interactions between platelets, neutrophils, and endothelial cells, thereby exerting an antiinflammatory effect. There was evidence of reduced myocardial injury and an improved postoperative course in those infants randomized to therapy.
Assessment of cardiovascular function and tissue oxygenation
The primary task in the critical care setting is to make a timely and accurate assessment of cardiovascular function, cardiac output, and tissue oxygenation. Studies have shown that estimations of these hemodynamic parameters based on routine or standard clinical parameters, such as the physical examination, heart rate, blood pressure, and urine output, are often discordant from measured values. Studies in children have shown that there is no correlation between estimations of cardiac output and systemic vascular resistance based on peripheral pulses, capillary refill, and peripheral to core body temperatures, and measured values of these parameters. Although the physical examination and the interpretation of standard hemodynamic parameters are essential parts of the assessment of cardiovascular function, studies have shown that the adjunctive use of technology such as near-infrared spectroscopy–derived tissue oxygenation and venous oximetry are invaluable tools in this assessment.
Venous Oximetry
Venous oximetry relies on the measurement of mixed venous oxygen saturations to evaluate the relationship between oxygen delivery (D o 2 ) and oxygen demand (V o 2 ), or oxygen transport balance, and in assessing the adequacy of tissue oxygenation ( Box 1 ). As D o 2 decreases, oxygen extraction increases to maintain adequate oxygen availability. As D o 2 decreases further, oxygen extraction and the oxygen extraction ratio continue to increase ( Box 2 , Fig. 1 ); as the oxygen extraction ratio exceeds 50% to 60%, serum lactate levels begin to increase as its production exceeds its clearance, defining the onset of anaerobic metabolism and the critical oxygen extraction ratio (see Box 2 ). Thus, oxygen extraction increases and becomes critical before serum lactate levels begin to increase. The critical oxygen extraction ratio is 50% to 60%, regardless of whether the perturbation in oxygen transport balance is caused by hypoxemia, anemia, low cardiac output, or an increase in oxygen demand.
Fick equation:
By ignoring the amount of oxygen dissolved in blood, the Fick equation may be simplified to:
V o 2 , oxygen consumption (mL/min); CO, cardiac output (L/min); Ca o 2 , arterial oxygen content (mL o 2 /dL); Cv o 2 , venous oxygen content (mL o 2 /dL); Sa o 2 , arterial oxygen saturation; Smv o 2 , mixed venous oxygen saturation; D o 2 , oxygen delivery (CO × Ca o 2 ; mLO 2 /min).
- A.
Oxygen extraction ratio ( o 2 ER)
Sa o 2 , arterial oxygen saturation; Smv o 2 , mixed venous oxygen saturation
- B.
Oxygen extraction ratios
25%, normal
30% to 40%, increased
40 to 50%, impending shock
>50% to 60%, shock, lactic acidosis
Based on mixed venous oxygen saturations.
Mixed venous oxygen saturations are seldom available because the use of pulmonary artery catheters has declined significantly over the last several years. Central venous oximetry is increasingly being used and studies have shown a good correlation between central venous (right atrium or superior vena cava) and pulmonary artery saturations (in the absence of left to right cardiac shunting). Studies have shown that the use of central venous oximetry to guide resuscitation in pediatric and adult septic shock and its use in managing patients following the Norwood procedure have led to improved survival.
Cerebral Near-infrared Spectroscopy
Cerebral near-infrared spectroscopy noninvasively measures cerebral oxygenation and, in doing so, assesses the relationship between cerebral oxygen delivery and oxygen demand or cerebral oxygen transport balance.
This technology was introduced into the clinical setting in the mid-1990s, when it was used to monitor cerebral oxygenation during cardiopulmonary bypass in adults. It has since been applied to pediatric cardiac surgery and, over the last several years, this technology has permeated pediatric critical care and pediatric cardiac critical care units. The first cerebral oximetry device to receive US Food and Drug Administration (FDA) approval was the INVOS system (Covidien Corp., Boulder, CO) ( Fig. 2 ).
