Porcine heparin replaces beef-derived heparin

Tom Nelson, RPh, clinical coordinator, Pharmacy Department, Children's Hospital of Wisconsin.

Last September, Children's Hospital of Wisconsin Pharmacy Department replaced beef heparin with porcine heparin after more than 10 years of use since beef source heparin no longer is being produced in the United States.

The Children's Hospital Hematology Lab has verified that the therapeutic partial thromboplastin time (PTT) levels for porcine heparin compare to the former bovine standard. However, the porcine heparin is much more sensitive than the beef heparin with a target activated PTT of 75-105 seconds versus 61-90 seconds. This requires a careful check when reviewing PTT results.

As with bovine heparin when the first PTT within the therapeutic range is achieved, the left-over plasma should be sent to the blood center for a heparin level. This should be done on the same sample from which the "therapeutic" PTT was obtained. If this sample has a therapeutic heparin level (0.2-0.4 units/ml by protamine neutralization assay or 0.35-0.7 units/ml by an anti-factor Xa assay), then the heparin drip should be adjusted according to the PTT dosing change schedule as heparin is monitored by the PTT. If the sample does not contain heparin in the therapeutic range, the hematologist should be contacted for recommendations to modify the therapeutic range for that specific patient. If a "stat" heparin level is needed, the Hematology service should be contacted. The range for activated clotting time (ACT) monitoring of heparin at the bedside of patients on extracorporeal membrane oxygenation (ECMO) is 220 to 250 seconds.

Nesiritide: A pediatric perspective

Brian Simpkins, PharmD, resident, Pharmacy Department, Children's Hospital of Wisconsin.

Nesiritide (Natrecor®, Scios Inc) is a synthetic form of human b-type natriuretic peptide (hBNP) that currently is FDA-approved for use in adults with acute decompensated congestive heart failure (CHF). Nesiritide recently was added to the Children's Hospital of Wisconsin formulary and is approved for use only on the third floor (Surgery Department and Intensive Care Units). 

Nesiritide is identical in structure and function to endogenous hBNP and therefore has the same mechanism of activity. Nesiritide binds to the guanylate cyclase receptor on vascular smooth muscle cells. This results in an increase in intracellular cGMP and results in net smooth muscle relaxation and vasodilatation (both arterial and venous). Data from clinical trials in adult patients with CHF have shown that nesiritide results in a balanced arterial and venous vasodilatation. As expected, nesiritide has been shown to result in a net coronary artery vasodilatation. From a cardiovascular standpoint, nesiritide results in a net decrease in pre-load, after-load and myocardial oxygen demand. 

From a renal standpoint, nesiritide has significant benefits.  Nesiritide causes afferent arteriole vasodilatation with efferent arteriole vasoconstriction, which results in an increase in glomerular filtration rate. Additionally, nesiritide has direct renal tubular activity that results in a net natriuresis. This means that in addition to its cardiac effects, nesiritide has the potential to improve renal function as well.

Hypotension is the most clinically significant adverse effect. This adverse effect necessitates increased monitoring (intenstive care unit) and was the main reason for the current use restriction. It is important to note the majority of hypotension associated with nesiritide use is following the bolus dose. The current literature supports this statement in that in the majority of patients on nesiritide who received treatment for hypotension, the hypotension occurred during, or just following, the bolus. It also is important to note that a low incidence of arrhythmias have been reported with nesiritide use. The arrhythmias more commonly are associated with the use of nesiritide in combination with another agent, although there is a small degree of de novo arrhythmia associated with nesiritide use. The incidence of rebound tachycardia also is very low, especially compared to other agents such as nitroglycerin and/or dobutamine.

Currently, the available data suggests that nesiritide has the potential for significant benefit for Children's Hospital patients. One potential role for nesiritide would be the perioperative heart patient who is not responding adequately to other therapy. Recent literature does not support first-line use of nesiritide and it appears that, at present, the role of nesiritide is in addition to milrinone in the patient who is not responding adequately. One theoretical benefit to using nesiritide in this manner is the potential for synergy with milrinone. There is a small amount of data from the adult world that supports this hypothesis. In patients who were on milrinone therapy when nesiritide was added, there was a noticeable increase in diuresis above what was expected. Additionally, the authors noted a decrease in pulmonary capillary wedge pressure that was greater than expected for nesiritide alone. These data support the hypothesis that the combination of nesiritide with milrinone would be synergistic in nature, although there is no definitive evidence in support of or refuting this claim.

The current recommended dose is a 2mcg/kg bolus over five to 10 minutes followed immediately by a 0.01mcg/kg/min infusion. The administration of the bolus over five to 10 minutes is recommended in order to minimize the risk of clinically significant hypotension when initiating therapy. Patients must be monitored for hypotension and other potential adverse effects throughout therapy.  Keep in mind, nesiritide has significant incompatibilities. Contacting the Pediatric Intensive Care Unit pharmacist before initiating therapy will minimize potential incompatibilities significantly.

Special Needs Family Center offers support and resources to patients and families

Many heart conditions are parts of syndromes that affect other body systems. For these special needs patients, help and support is available through the Special Needs Family Center, located at Children's Hospital of Wisconsin. Staffed by parents of children and young adults with special health care needs, the center offers parent-to-parent support, referrals to local programs, information about special education, funding options and transition issues. The center lending library contains thousands of books, videos and articles on a variety of health conditions and other topics. To access the center, visit www.specialneedsfamilycenter.org, or call (414) 266-6333, or toll-free at (800) 234-5437.

Perfusion strategies for operative neuroprotection

James Groneck, BS, CCP, perfusionist, Herma Heart Center, Children's Hospital of Wisconsin.

During the past several decades, overall mortality rates for surgical repair of congenital heart disease have steadily declined. This is due, in part, to improved perfusion products and techniques. Despite this, neurologic morbidity has not seen the same level of decline and remains to be an area of major concern. In recent years the focus of attention has shifted from mortality to the short and longer-term neurodevelopmental issues that affect this patient population.
Neurologic injury can occur anytime during the peri-operative period and some patients may experience conditions that can lead to central nervous system (CNS) injury before arriving to the operating room for surgical repair. Hypoxia, low cardiac output and the presence of aorto-pulmonary collaterals can lead to conditions of inadequate oxygen delivery and cerebral hypoperfusion. Primary cerebral vascular disease often is present in children with chromosomal abnormalities and some patients may be genetically predisposed to be less tolerant of cerebral insults, delaying their recovery after cerebral ischemia.

The conduct of perfusion is very different for neonates and children than in adults. Children sometimes will experience extreme levels of hemodilution, temperature changes, lower perfusion pressures and flow rates. These factors will alter cerebral autoregulation, cerebral blood flow and play a role in neurologic outcomes after surgery. The cognitive effects of cardiopulmonary bypass (CPB) in adults have been well documented, but the mechanisms of injury may be very different from those that occur in children, therefore the same strategies to reduce cerebral injury may not apply to both groups. Operative brain injury in children often is related to periods of cerebral hypoperfusion or mismatches with cerebral oxygen supply and demand. Children with intracardiac shunts, or those who have single ventricle physiology, additionally are at risk for systemic air embolization. Conversely in the adult population, neurologic injury is thought to be mainly from atherosclerotic emboli. So as congenital heart disease (CHD) patients age, and adult CHD programs continue to grow, it is important for clinicians to have a broad understanding of the potential causes of neurologic injury unique to patients of all ages.

The past 10 years have been an exciting time for pediatric perfusionists. Many changes have occurred with equipment and techniques that now provide us with the opportunity to deliver support with systems designed specifically for even the smallest patients. Longer-term neurodevelopmental studies have been published and have helped us better understand the impact various perfusion management techniques have on the brain. The two schools of thought regarding the optimal pH management while on CPB, alpha-stat or pH-stat, have long been debated. However, most would agree that when deep hypothermia is used and cerebral autoregulation is lost, the higher partial pressure of carbon dioxide afforded with pH-stat management provides increased blood flow to the brain and probably cools it more evenly and thoroughly, making it the preferred technique. During periods of moderate hypothermia, the advantage of one blood gas strategy over the other is not as clear. Higher hematocrits during bypass will improve tissue oxygenation, and hematocrits in the 30 percent range have become very common in pediatric perfusion. Selective cerebral perfusion techniques now are used and in some centers, have nearly eliminated the use of deep hypothermic circulatory arrest (DHCA) for complex aortic arch repairs. One of the newer tools at our disposal is cerebral near infrared spectroscopy (NIRS). While the measurement of venous blood saturations while on bypass has been a standard for years, this measurement only gives us an indication of the adequacy of whole body perfusion and the reported value is the sum of many vascular beds. By using NIRS, we can assess an approximation of cerebral venous oxygen saturation in real time and make immediate changes to improve oxygen delivery to the brain if needed. NIRS sensors measure only saturations in the frontal lobe of the brain, so certain assumptions must be made about global brain perfusion. Despite these limitations, this technology now gives us another piece of information that was previously unavailable.

Cardiac surgical teams, now more than ever, are focused on what is happening to the brain during bypass and as evidence has become available, have tailored practices to optimize outcomes. It would be inaccurate to suggest we have not been concerned with neurodevelopmental issues from the beginning, but with recent and ongoing clinical data, emerging technologies and the potential for pharmocologic ischemic pre-conditioning, over time we are positioned to reduce the short and long-term neurologic morbidity we experience today.

Malignant hyperthermia

Alexis Sullivan, RN, BSN, pediatric nurse, Pediatric Intensive Care Unit, Children's Hospital of Wisconsin.

A summary of a presentation given by Susan Nicolson, MD, anesthesiologist, Children's Hospital of Philadelphia, at the 8th annual Update on Pediatric Cardiovascular Disease, Feb. 16-20, 2005 in Orlando, sponsored by the Cardiac Center at Children's Hospital of Phildelphia.

Malignant hyperthermia is an inherited disorder of skeletal muscles and can be triggered by the administration of succinylcholine or inhaled anesthetic gases like isoflurane. Malignant hyperthermia may not occur with a patient's first exposure to anesthesia, but rather a subsequent exposure. This disorder is found to be more common in children than adults.

Onset of this type of hyperthermia can be either during anesthesia or when emerging from anesthesia. Malignant hyperthermia occurs when there is a loss of control of intracellular calcium, which increases skeletal muscle metabolism. In addition to hyperthermia, other signs and symptoms of this disorder may include increased end tital CO2, muscle rigidity and rhabdomyolysis. These patients also may be tachycardic, acidotic and hyperkalemic.

Treatment includes discontinuing the inhaled agent, hyperventilation with 100 percent oxygen, cooling blanket and placement of arterial line if not already in for assessment of arterial blood gases, CK, coags and potassium level. Placement of a foley also is indicated to check for myoglobinurea. Despite aggressive cooling measures, this has been very difficult to treat and has had a high incidence of mortality.

Dantrolene is a medication that has shown much success in the treatment of malignant hyperthermia with adromatic decrease in mortality. Dantrolene prevents the release of calcium from cells. It is given IV push and can be repeated after 20 to 40 minutes if not initially effective. After the intial dose it is administered every four to six hours for the next 24 to 36 hours. A toll-free hotline is available for health care personnel as a resource in these rare, but potentially fatal patient situations. Call (800) MH HYPER or (800) 644-9737 for questions about treatment options.

Herma Heart Center names manager

Children's Hospital of Wisconsin has named Matt Groninger as manager of Herma Heart Center. Groninger joined Children's Hospital in July 2004 as an administrative fellow. He received a bachelor's degree in Economics from Emory University, Atlanta, in May 2001, and completed a master's in Health Services Administration from the University of Kansas Medical Center in May 2004. Groninger resides in New Berlin, Wis.

"We are thrilled that Matt has assumed the role of manager of the heart center," said Maryanne Kessel, director, Herma Heart Center. "His proven leadership skills in health care will be invaluable to the further development of center programs and expertise as we continually strive to provide the best cardiac care to children of all ages."