Fenoldopam (Corlopam®) Vasodilator has properties to protect renal function

Mary Szulczewski, RPh, pediatric pharmacist, Children's Hospital of Wisconsin

In the immediate postoperative phase following correction of congenital heart defects, transplants or other vasoconstrictive states, patients may require vasodilators (among other drugs) to decrease blood pressure and improve circulation. The most common vasodilators include milrinone and/or nitroprusside. Occasionally esmolol, nicardipine and nitroglycerin also may be used. In addition, low-dose dopamine is used to protect renal function in these patients since it has long been known that vascular surgery can lead to impaired renal function. The combination of milrinone (with or without nitroprusside) and dopamine generally is needed only for a day or two after surgery. During that time, the patient is started on captopril orally if vasodilatation (after load reducation) is required chronically. Additional drugs required may include diuretics and digoxin.

Fenoldopam (Corlopam®) has been used occasionally in the Pediatric Intensive Care Unit (PICU) at Children's Hospital of Wisconsin for patients that require high doses of vasodilators where toxicity becomes a problem. Fenoldopam has been used in place of nitroprusside when thiocyanate toxicity is a concern due to escalating doses. Milrinone can be used in combination with fenoldopam because of its low toxicity profile.

Fenoldopam was approved by the FDA in 1997 for in-hospital, short-term (up to 48 hours) management of severe hypertension when rapid but reversible reduction of blood pressure is indicated, including malignant hypertension with deteriorating end-organ function in adults. As with many drugs used at Children's Hospital, the FDA offers no pediatric dosing indications for fenoldopam.

Fenoldopam is a rapid-acting vasodilator. It reduces blood pressure as adequately as nitroprusside, however, fenoldopam is a dopamine-1 receptor agonist, which gives it some unique properties not seen with other vasodilators. In addition to reducing blood pressure, fenoldopam has been shown to improve renal function. It causes vasodilatation in coronary, renal, mesenteric and peripheral arteries. It appears there is more vasodilatation seen in the renal arteries than other vascular beds.

Fenoldopam is administered as a constant intravenous infusion at rates ranging from 0.01 to 1.6 mcg/kg/minute. Studies in children indicate dosage requirements are higher than in adults. Starting dose for children is 0.1 mcg/kg/minute. Doses of 0.1 to 0.8 mcg/kg/minute usually result in significant dose-dependent reduction in blood pressure. Doses greater than 0.8 mcg/kg/minute have been associated with higher frequency of side effects without much added benefit in blood pressure reduction. The elimination half-life is five minutes in mild to moderate hypertension and steady state is attained in about 20 minutes. There is no difference in elimination in patients in renal failure so no dose adjustment is required. No adjustment is required in hepatic failure.

The dose of fenoldopam should be titrated based on response. Maximal effect of a dose change is seen within 20 minutes. Increase the rate by 0.05 mcg/kg/minute every 20 minutes until the desired effect is reached. Maximal decrease in blood pressure usually is achieved in one to four hours. Studies on the length of therapy have shown the drug is effective for up to 48 hours without significant loss of effect. There is no information for use longer than 48 hours.

Studies have shown that use of fenoldopam to treat hypertension also has improved renal function. Fenoldopam increases urine output by as much as 50 percent and urinary sodium excretion by 300 percent. Renal blood flow is increased, as is glomerular filtration rate. These effects may be beneficial to patients who suffer from acute renal failure in the immediate post-operative phase of recovery.

Side effects associated with fenoldopam are similar to those seen with other vasodilators and include headache, dizziness, hypotension, flushing and tachycardia. Most adverse effects are mild, occur within the first 24 hours of treatment and diminish therafter. There is no thiocyanate toxicity as is seen with nitroprusside.

Two significant side effects unique to fenoldopam include a flattening of the T waves on ECG and increased intraocular pressure.

Drug interactions with other cardiac drugs are not significant except ACE-inhibitors potenitate the natriuretic effects of fenoldopam. A more marked diuresis might be anticipated in patients treated with fenoldopam and one of these drugs.

Monitoring parameters include blood pressure, heart rate, ECG monitoring for changes in T wave, electrolyte changes including hyponatremia and hypokalemia.

Transition to oral therapy with another drug can begin any time after blood pressure is stabilized, with the rate of fenoldopam reduced gradually as oral therapy becomes effective. Fenoldopam can be stopped abruptly and has not been associated with rebound hypertension. Effects persist for some time after drug is stopped.

Drip preparation and compatibilities
The PICU pharmacy prepares fenoldopam as a drip with a concentration of 60 times the patient's weight. This is the same way milrinone and nitroprusside drips are prepared. It is diluted with D5W. Limited experience in the PICU indicates that the prepared drip is compatible with other cardiac drips and can be added at the Y site. Please consult the PICU pharmacist for specific compatibility information at (414) 266-3035.

Beyond survival: Exploring the psychosocial implications of congenital heart disease

Kathy Mussatto, RN, BSN, cardiothoracic surgery research coordinator; and Cheryl Brosig, PhD, pediatric psychologist, Children's Hospital of Wisconsin.

Improved survival, reduced morbidity and longer duration of follow up for virtually all forms of congenital heart disease (CHD) mandate the systematic assessment of psychosocial variables as important measures of the outcomes of this disease. These psychosocial factors can include neurodevelopmental outcomes, health-related quality of life (QOL), and measures of the impact on the family of a child with CHD such as parenting stress or expectations and the availability of support systems.

Today, centers specializing in the treatment of CHD routinely report survival rates > 95 percent for most lesions requiring surgical repair. Most CHD subjects undergo early surgical treatment and benefit from dramatic improvements in both medical and surgical management strategies. For many children with the most complex forms of CHD this success has been very recent. Children's Hospital of Wisconsin has demonstrated excellent results with the management of CHD, averaging more than 320 open heart surgical procedures per year with <3 percent early mortality (1998-2002). Of particular note are the Children's Hospital results with complex neonatal heart repairs. For the five-year period noted above, >15 percent of the open heart procedures were performed in neonates younger than 31 days of age with a 94 percent early survival rate. Given these results, the population of CHD survivors is growing exponentially and the ability to assess long-term outcomes in these subjects and their families has become both more feasible and more significant.

Staff from Children's Hospital currently are involved in a study to begin to explore some of the psychosocial outcomes of CHD. The study titled Neurodevelopmental Outcome, Quality of Life, and Impact on the Family in Survivors of Complex Congenital Heart Disease: A Pilot Study, is being investigated by Kathy Mussatto, RN, Cheryl Brosig, PhD, Ramesh Sachdeva, MD, James Tweddell, MD, Andrew Pelech, MD, and S. Bert Litwin, MD. All are on staff at Children's Hospital. In addition, Sachdeva, Tweddell and Pelech are on the faculty of the Medical College of Wisconsin. The study has been reviewed and approved by the Children's Hospital Institutional Review Board. The research is being supported in part by a grant from the Julie Lathrop Nursing Research Fund at Children's Hospital. The aim of the study is to systematically assess preschool-age survivors of CHD and their families using a variety of validated tests and surveys designed to measure psychosocial variables. The study goal is a sample of 30 children ages 3 to 6 years. Children with transposition of the great arteries (TGA) repaired with the arterial switch procedure will comprise approximately half of the sample, the remainder will include children with hypoplastic left heart syndrome (HLHS) or other single ventricle heart disease, that underwent initial surgical palliation with the Norwood procedure.

These specific diagnostic groups were selected because both groups underwent their initial surgical repair during the neonatal period and all received their care at Children's Hospital. In addition, several studies have reported results on the neurocognitive outcomes of TGA patients and will provide comparative data for the findings in this study. While patients with TGA typically undergo a single surgical procedure, HLHS patients are treated with a staged surgical approach typically including three open heart procedures before the age of 4 years. This fact would presumably put the HLHS patients at a greater degree of risk for negative psychosocial impact, however no study has compared age-matched, contemporary samples of these two groups. Preschool-age children were selected primarily because recent cohorts of subjects have benefited from several advancements in their perioperative care and because neurocognitive measures obtained in the preschool-age child are more predictive of long-term neurocogitive achievement than those obtained from younger children or infants.

The study currently is underway with 18 of the 30 children having been evaluated. This article will review the scientific basis for the study and the instruments chosen as well as some preliminary findings.

Neurodevelopmental assessment
Children with CHD face several risks for neurologic injury. These risks can occur throughout their disease process and include preoperative, intraoperative, postoperative and long-term factors. Recent studies examining neurodevelopmental outcomes have focused primarily on children with complex CHD. It is believed that "simple" CHD puts the subject at minimal risk for neurologic injury, however large studies in this population have not been conducted. Research results are impacted by the diagnoses of subjects assessed, the era in which subjects underwent surgery, the outcome measures utilized and the age at testing. Several studies have reported on CHD subjects that demonstrated IQ scores within the low range of normal with the mean falling below that reported for the healthy population. In various samples, 5 to 25 percent of subjects scored at levels considered to indicate intellectual dysfunction with several utilizing some special education services. Mild learning disabilities and hyperactivity disorders appear to be relatively common. Neurological abnormalities are common however most are mild in nature. Severe deficits are reported to occur in < 10 percent of subjects evaluated. These abnormalities include speech or attention disorders, hypotonia, microcephaly and other mild developmental delays.

In the present study, the pediatric psychologist completes several measures with the child to assess neurodevelopmental achievement. They include:

• McCarthy Scales of Children's Abilities (MSCA) - assesses cognitive function on six scales; overall IQ, verbal, perceptual performance, quantitative, memory and motor.
• Woodcock-Johnson Tests of Achievement 3rd Ed. (WJIII) - assesses scholastic aptitudes, achievement and school readiness.
• Receptive One-Word Vocabulary Test (ROWVT) - receptive language abilities.
• Expressive One-Word Vocabulary Test (EOWVT) - expressive language abilities.
• Developmental Test of Visual-Motor Integration (VMI) - tests complex processing skills associated with perceptual motor skills, for example hand-eye coordination.

The parent of the child, primarily the mother, also completes two instruments frequently utilized in pediatric developmental assessment. These include:

• Child Behavior Checklist (CBCL) - behavioral assessment based on parental observations.
• Child Development Inventory (CDI) - developmental assessment based on parent report of observed behavior.

Results in the first 13 subjects evaluated in the Children's Hospital study have identified a mean score on the General Cognitive Index (IQ) of the McCarthy Scale of 85.7, significantly lower than the normative mean of 100 ± 16, p < 0.01. (See Figure 1).

Scores on the verbal, performance, quantitative and memory scales of the McCarthy as well as receptive and expressive vocabulary scores on other measures were within the normal range. Visual-motor integration (VMI), spelling and applied problems on the Woodcock-Johnson test and motor score on the McCarthy all fell significantly lower than the normative mean (p < 0.02). The VMI scores demonstrated the most significant variance from normal, a finding that also has been cited in previous research. The amount of data collected thus far does not support statistical comparisons between the two diagnostic groups, however the HLHS group scored lower than the TGA group on all neurodevelopmental indices completed.

Psychosocial assessments
The examination of other psychosocial outcomes in subjects with CHD has received considerably less attention in the literature. Traditionally, we have relied on clinical parameters such as morbidity, mortality and cardiac function to measure outcomes. However, some research has questioned the link between clinical status and the patient's subjective report of their overall health status. The impact of CHD may be subtle in many important psychosocial domains such as a tendency toward an increased level of behavior problems. Parents of children with newly diagnosed CHD however, have a keen interest in these issues.

The assessment of health-related quality of life provides a subjective measure of outcome that incorporates the unique perspective of the subject. In addition, measures of parenting stress, behaviors and the overall impact on the family may add information to understanding the experience of living with CHD. In some studies parents of children with CHD reported higher levels of stress and financial strain. In addition, the amount of stress and social support available has been shown to moderate child adjustment. In the current study, several instruments are completed by a primary caregiver to shed light on these topics. They include:

• Pediatric Quality of Life Inventory (PedsQL) Parent Report for Children ages 2-4 or 5-7 years.
• Parent Behavior Checklist (PBC) - parenting style and expectations.
• Parenting Stress Index (PSI) - family stress measured in three domains: child, parent and situational.
• Impact on the Family Scale (IOFS) - family impact of chronic illness.

Parents attending the neurodevelopmental evaluation also have completed a semi-structured qualitative interview with one of the principal investigators focusing on their experience with CHD.

In the current study, parents are providing proxy-reports of their child's quality of life using the PedsQL parent report. In the sample surveyed thus far, parents have reported a low incidence of CHD impact on physical, emotional, social or school domains. One mother of a child with symptomatic heart disease commented, "He's definitely limited compared to other children but it doesn't seem to bother him." In a related study at Children's Hospital, 51 subjects with CHD (age 8-28 years) completed QOL surveys as well as 81 parents of subjects (age 2-18 years) with CHD. While the CHD subjects reported QOL that did not differ from normative samples, parents of children with CHD reported QOL scores that were lower than healthy samples for overall QOL, physical, social and school functioning (p<0.05). (See Figures 2 and 3).

The positive and negative impact of CHD on a family has not been explored in great detail. The current study utilizes the Impact on the Family Scale (IOFS), a 30-item survey validated in families of children with chronic illness. In the surveys evaluated thus far parents have reported:

• 100 percent - Because of what we have shared, we are a closer family.
• 93 percent - I try to treat my child as if he/she were a "normal" child.
• 73 percent - Learning to manage my child's illness has made me feel better about myself.
• 73 percent - I worry what will happen to my child in the future.
• 47 percent - Time is lost from work because of hospital appointments.
• 40 percent - Having a child with an illness makes me worry about my other children's health.

On the Child Behavior Checklist, 31 percent of subjects scored within normal limits, however 38 percent demonstrated elevated total problem scores. Results on the Parent Behavior Checklist and Stress Index have fallen essentially within the normal range however some interesting themes have been identified. Twenty percent of parents reported feelings of isolation and 33 percent report that their child has qualities that make it difficult to fulfill the parent role.

Summary
There are significant limitations of research in psychosocial domains such as these. Many of the survey instruments available rely on a completely subjective report from the child or parent. Similar to the experience of pain, only the subject really can tell us what it is like for them. There also may be a significant sample bias in those who choose to participate in this type of research. Subjects and parents could be attempting to tell us what they think we want to hear or only those feeling that they have had positive outcomes may be inclined to participate.

Despite these limitations, ongoing exploration into the psychosocial implications of CHD is warranted. CHD remains the most common form of birth defect reported to the March of Dimes. Increasingly encouraging results with even the most complex forms of CHD demand the need for ongoing assessment of outcomes that are not limited strictly to clinical parameters. Results of the ongoing Children's Hospital study described will be reported again when completed. It is hoped that data from this study will identify trends in outcomes and the instruments most sensitive to potential problems. Further studies on a larger scale then will be pursued. Ultimately, there is potential that this research will allow us to implement an assessment scheme to identify children and families at risk for problems and to devise interventions to diminish any negative psychosocial impact of CHD.

Nutrition for children with congenital heart disease

Joyce Owens, RD, CD, CNSD, clinical dietitian, Children's Hospital of Wisconsin.

Infants and children with congenital heart disease (CHD) present special nutritional challenges. It is not uncommon to have some degree of growth failure. In almost all cases, nutritional intervention is required to ensure adequate nutritional intake to decrease the risk of malnutrition and promote weight gain, linear growth and age-appropriate development.

With CHD, many factors can interfere with nutritional intake. These include:

• Poor appetite.
• Early satiety.
• Decreased absorption of nutrients.
• Fatigue during eating.
• Feeding difficulties.
• Medications that decrease appetite.

There are many forms of CHD. The type of defect as well as the severity of the defect greatly influences nutritional needs. At times, nutritional intake may be appropriate for the child's age. However, due to increased energy expenditure, it may not be enough to promote proper growth or catch-up growth.

During infancy, growth occurs at a rate greater than any other period of childhood. This makes early and frequent nutritional monitoring imperative. Nutritional needs must be assessed and any feeding plan must be individualized to meet the specific needs of the child.

Many strategies are available to help meet the increased needs of infants and children with CHD. Breastmilk and infants' formulas can be fortified/concentrated to increase caloric density and different modulars and/or additives also are available to help increase nutritional intake if needed.

Prior to a surgical procedure, it is important to maintain adequate nutritional intake for the following reasons:

• Weight gain for surgery can be achieved faster.
• The risk for infections can be decreased, which can help speed recovery.

After infants are introduced to solids and transitioned from breastmilk/formula to whole milk, a high calorie diet may be warranted to help ensure adequate nutritional intake. In some cases, a high calorie supplement may be needed to help achieve optimal nutritional intake, growth and development.

A registered dietitian, who works in conjunction with primary care physicians, is available to assess the infant's/chid's individual nutritional needs and to help design a workable plan to promote optimal growth and development. Regular follow-up visits are essential to properly assess growth and to re-evaluate nutritional needs for the child.