Temperature Regulation in the Operating Room

Steven Butz, MD, pediatric anesthesiologist, Children's Hospital of Wisconsin; assistant professor of Anesthesiology, Medical College of Wisconsin.

As humans, we are homeothermic, capable of regulating our core temperatures over a broad range of external temperatures. Infants are less capable of regulating their temperature mostly because of their large surface area to volume ratio. Anesthetics further impair a person's response to temperature changes by preventing movement (shivering) and lowering the threshold that triggers non-shivering thermogenesis. Anesthesia also impairs vasoconstriction and allows heat to be conducted from the body's core to its surface and be radiated out to the operating room.

It is very important to manage patient body temperature during open-heart surgery to preserve organ function. Colder temperatures reduce metabolic needs and oxygen consumption. Skeletal muscles and limbs are most affected followed by the kidneys, splanchnic bed, heart and brain. Hypothermia also decreases the metabolism of drug and anesthetic requirements. This, combined with lower oxygen needs, permits lower pump flows while on bypass, which reduces bleeding and trauma to the blood's cellular elements.

Hypothermia is not all good, but the negative aspects are greatly outweighed by the benefits.

The clotting system is inhibited and there is a greater incidence of cardiac arrhythmias. The heart also slows as it cools, but contractility is not affected. Ventilation would slow if the patient was breathing and the lungs would bronchodilate. The kidneys lose their ability to concentrate urine and retain glucose; both can increase urine output. Hyperglycemia occurs secondary to norepinephrine release causing glyconeogenesis and gylogenolysis combined with insulin resistance. Hemoglobin dissociation curve shifts to retain oxygen but is offset by the lower oxygen need. Red blood cells change their shape but hemodilution and heparinization prevent slugging.

Patients are cooled and warmed using several methods of heat transfer. During dissection and exposure of the heart prior to bypass, the patient is allowed to passively cool through conduction and radiation to the cooler operating room. Once the cannulae for bypass are in place, a water blanket beneath the patient actively cools him or her. When bypass has commenced, cooling is rapidly achieved by a counter-current system within the oxygenator. Here, cold water is passed through at a maximum of 8° C difference from the patient's blood temperature. The coldest water is 12° C. The anesthesiologist gives no IV fluid at this time and respiration is suspended. The operating room is cooled to nearly 60° F. Ice packs may be placed under and around the heart while it is being repaired. Cardioplegia solutions are cooled or come through an ice bath and any irrigation solutions also are cooled. If deep, hypothermic circulatory arrest (DHCA) is used, the head is packed with ice bags under the drapes.

Rewarming is accomplished in a similar fashion. The water through the counter-current system is warmed to a maximum 8° difference from the patient's venous blood. The warmest water is 40° C and the patient is warmed to 35° to 36° C prior to being taken off bypass. The water blanket also is warmed and the patient is ventilated with warm, humidified air to reduce evaporative losses. The operating room is heated to above 80° F after the aortic cross-clamp is removed. Fluids given after separation from bypass are passed through a warmer. Irrigation solutions also are heated.

Brain temperature is the gold standard for temperature measurement while heating and cooling. However, there is no easy access to evaluate the temperature of the brain so we have to use secondary indicators. There are many sites to monitor the patient's temperature but they differ in relationship to the body's true core temperature and may be affected by different variables. In the operating room, the patient has a temperature probe incorporated into the urinary catheter to obtain bladder temperature. This is affected by the amount of urine output. For patients that are too small to have a bladder temperature sensor, a rectal probe is placed. These are accurate providing there is not a great deal of stool in the vault. A nasopharyngeal temperature probe is placed as a second site and the perfusionists measure arterial and venous blood temperatures. One study indicates that three temperature sites should be used to best estimate core temperature so that an outlaying measurement may be confidently disregarded.

Changes in pH need to be accounted for to maintain cellular functions while the patient is cooled. There are two strategies to manage pH: alpha-stat and pH-stat. Alpha-stat management keeps the ionization of the imidazole ring of histidine constant. This is because the charge of histidine is critical in many enzyme systems. Poikilothermic animals use this strategy to keep organ systems functioning at an optimal level through wide temperature variations. As a result of the alpha-stat strategy, the patient becomes more alkalotic as he or she is cooled because pCO2 levels are kept constant. (Carbon dioxide becomes more soluble with decreasing temperatures.)

During pH stat management, the patient is kept at a pH of 7.4. Carbon dioxide is added to accomplish this and the patients become more acidotic. This may be beneficial to increase cerebral blood flow and is used in cases of DHCA in the operating room.

The remainder of the time, an alpha-stat management strategy is used. Interestingly, pH-stat management is similar to the physiology of hibernating mammals. Upon arousal, the first thing they do is hyperventilate to remove the CO2 and resume an alpha-stat management to optimize organ function.

Amiodarone (Cordarone®): An Old Drug with New Importance

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

The FDA first approved Amiodarone in 1985 and it has been available for intravenous use since 1995. The intravenous indication of amiodarone has been for treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia in patients refractory to other therapies.

The new proposed indication for amiodarone is for acute treatment and prophylaxis of life-threatening ventricular tachycardia or ventricular fibrillation.

Amiodarone is a group III antiarrhythmic. This means it produces a prolongation of repolarization (phase 3). The other group III agents are bretylium (currently in short supply in the USA) and sotalol (an oral only medication).

The electrophysiology and electrocardiogram effects of amiodarone are:

• Decreased automaticity at the SA node.
• Decreased conduction velocity in the atrium, AV node and His-Purkinje.
• Increased refractory period in atrium, AV node, His-Purkinje, ventricle and accessory pathways.
• ECG changes: decreased heart rate, increased PR interval and QRS complex, and significantly increased QT and ST intervals.

The new Pediatric Advanced Life Support (PALS) guidelines were published in Circulation 2000; 102 (suppl I): 291-342. In these guidelines, amiodarone is the first antiarrhythmic treatment of VF/VT in cardiac arrest ahead of lidocaine. The overall order being defibrillation, administer epinephrine, attempt defribrillation, administer antiarrhythmic.

New recommendations were developed by the American Heart Association (AHA) for the treatment of pulseless ventricular fibrillation or tachycardia after reviewing existing trials.

Their evaluation included the Arrest Trial, which compared the 1992 ACLS guidelines with and without IV amiodarone in shock-refractory VT/VF cardiac arrest. The study used adults in a randomized, double-blind, placebo-controlled prehospital setting. Amiodarone 300 mg or placebo was administered by rapid bolus.

The conclusion was that amiodarone significantly and independently improved the rate of survival before admission to the hospital after shock-refractory cardiac arrest. The benefit was observed in all major subgroups including patients with VF, asystole, recurrent VF and persistent VT.

Lidocaine now is an alternative agent for life threatening VT/VF. Analysis of 10 lidocaine trials demonstrated four positive lidocaine results and six studies with negative lidocaine results. One prominent study showed no difference in survival one hour after cardiac arrest with or without lidocaine. The AHA classified lidocaine as indeterminate, in other words, no qualified recommendations along with inconsistent and contradictory results.

The AHA also recommends use of a single antiarrhythmic based on arrhythmia diagnosis and patient status.

Dosing: Pediatric amiodarone dosing is a rapid bolus of 5 mg/kg for pulseless VT/VF. In contrast, the administration of amiodarone for recurrent VT is 5mg/kg over 20-60 minutes as an infusion which may be repeated up to a maximum of 15 mg/kg/day.

Pharmacokinetics: Amiodarone is a highly lipid soluble antiarrhythmic with complex pharmacology. Hypotension is the main acute side effect of intravenous administration. IV administration results in a rapid onset of effect but amiodarone redistributes to 10 percent of peak serum levels within 30-45 minutes of completion of infusion. Amiodarone has a terminal half-life of up to 40 days.

Don't Know? Ask a Social Worker

Darcia Behrens, MSW, CICSW, designated social worker for cardiac patients at Children's Hospital of Wisconsin.

Having been affiliated with the Social Work Program at Children's Hospital for over 15 years, I would characterize medical social work as the last generalist profession in the highly specialized world of hospital medicine. Many times you will hear one of my colleagues say to a parent, "I may not know the answer to your question but I will know who to ask or where to go to find out."

The questions posed to social workers vary widely from the most basic necessities of life such as food and shelter to complicated financial and legal problems including child protection and custody issues. We often participate in hospital care conferences for children with congenital heart disease to stay informed about a child's medical needs and also to serve as an advocate for parents who may feel out of their element and a loss of control in the high-tech medical environment.

Social workers also act as the information link to the extended family so parents do not have to become the medical "expert" at a time when their child is ill and their stress is very high.

The job of a social worker is in constant motion and changes in accordance with patient/parent needs and the needs of the hospital. No day is exactly like the one before or the one ahead, which for me is part of the appeal and the challenge.

Social workers at Children's Hospital of Wisconsin are available to provide family assessment services, referrals for community medical and counseling follow-up, discharge planning service, education for families and staff, crisis intervention services and consultation to families and staff.

The Heart Center, Cardiovascular Surgery and Heart Transplant programs contribute an increasing number of referrals to social work services at Children's Hospital of Wisconsin. The primary areas of inpatient social work referrals are from the Neonatal Intensive Care Unit, Pediatric Intensive Care Unit and Intermediate Care Unit. Outpatient referrals come from the Heart Center, Day Surgery/Pre-Op Clinic and direct phone calls from parents and staff about particular problems or concerns.

Anyone can make a referral to the Social Work Program. Hospital staff do so by placing an order into the Sunrise Clinical Manager computer system. Parents can call (414) 266-2800 or 1-800-556-8090 and ask the operator to forward the call to ext. 2800. Parents requesting help should indicate whether they have worked with a Children's Hospital social worker in the past.

Social work services are free to patients and their families.

Clinical Research Trial Updates - Milrinone and Esmolol

Kathy Mussatto, RN, CV Surgery Clinical Research Coordinator, Children's Hospital of Wisconsin, and
Beth Newbury Whitstone, RN, MA, Cardiology Clinical Research Coordinator, Children's Hospital of Wisconsin

Two new multi-center clinical drug studies involving children undergoing cardiac surgery have recently been initiated at Children's Hospital of Wisconsin.

The Milrinone clinical trial got underway in September. Seven patients were enrolled as of the beginning of December.

This postoperative clinical trial involves patients younger than 6 undergoing biventricular repair of congenital heart disease. The purpose of this study is to determine the role of Milrinone in preventing low cardiac output syndrome after cardiopulmonary bypass. Patients who meet inclusion criteria are randomized to a 36-hour infusion of high-dose Milrinone, low-dose Milrinone, or placebo within an hour and a half of their arrival in the Pediatric Intensive Care Unit. Dosing and pharmackinetics are being evaluated.

Investigators on this trial include Stuart Berger, MD, Jim Tweddell, MD, Nancy Ghanayem, MD, and S. Bert Litwin, MD. The trial is expected to enroll 36 patients by June. These clinical drug trials could not take place without the support and assistance of many members of the health care team, including physicians, nurses and ancillary staff. For example, the responsibilities of the PICU staff nurses include monitoring the infusion, ensuring that scheduled labs are drawn and notifying the study coordinators of any adverse events during the child's hospitalization.

The second clinical trial is designed to evaluate the efficacy and safety of Esmolol for the treatment of hypertension in patients undergoing repair of coarctation of the aorta. Three doses of Esmolol are being compared and a pharmacokinetic profile will be generated. Study personnel are blinded as to the patients' dosing assignment. If the child's systolic blood pressure rises above a set threshold within 30 minutes of cross-clamp release, the patient receives an Esmolol bolus followed by a 15-minute infusion. Change in systolic blood pressure and need for rescue medication five minutes after the bolus dose are the study's primary efficacy endpoints. Enrollment in the study began in September.

Currently, there are eight active sites with plans for nine more to be initiated in the coming months. A total of 100 patients will be treated under this protocol in the next year. We have enrolled one child at Children's Hospital of Wisconsin.

If you have questions about either of these clinical research trials, contact one of us: Kathy Mussatto (414) 266-2073 or Beth Whitstone (414) 266-2384.

Protection of the Infant Heart During Surgical Repair of Congenital Defects: Prospects for Future Therapies

John E. Baker, PhD, associate professor, Pediatric Surgery, Medical College of Wisconsin.

Each year, more than 25,000 children undergo corrective surgery for cardiac birth defects. Advances in surgical techniques have made primary correction or palliation of almost all congenital cardiac defects possible. Early surgical intervention is important to promote more normal development.

Surgical repair of congenital cardiac defects in children that involves the use of cardiopulmonary bypass frequently requires a period of myocardial ischemia. Even though these types of repairs are carried out routinely, our understanding of the mechanisms of resistance to myocardial ischemia and methods of cardioprotection in the immature heart remains limited. Incomplete cardioprotection in infants and children after surgical repair of congenital heart defects has been demonstrated by a deterioration in heart function post-operatively. It would be desirable to alter current techniques of myocardial management during surgery to provide better myocardial protection for children with congenital heart disease.

Many infants who undergo cardiac surgery in the first year of life have cyanotic heart defects where the myocardium is chronically perfused with hypoxic blood. By elucidating the impact that prolonged periods of hypoxia exert upon resistance to subsequent ischemia, we should be able to understand and improve cardioprotection in children with congenital heart defects.

To investigate the effects of chronic hypoxia on myocardial function and the signal transduction mechanism responsible for subsequent cardioprotection, we developed an animal model in which rabbits are raised from birth in a hypoxic environment. Our model simulates the essential characteristics of cyanotic congenital heart disease. The model is characterized by decreased arterial oxygen levels, polycythemia, right ventricular hypertrophy, decreased weight gain, and overall failure to thrive - characteristics similar to those seen in children with cyanotic congenital heart defects. The resulting changes in the physiology and biochemistry of the heart are achieved without surgical manipulation.

This model of chronic hypoxia has demonstrated that hypoxia from birth increases resistance of the heart to surgical ischemia. Our model may be used to improve our understanding of the signaling pathways responsible for cardioprotection. Understanding these pathways may lead to the development of therapeutic strategies for the intraoperative management of the human infant myocardium.

Protein kinase signaling pathways in adults are activated in response to the stress of oxygen deprivation to confer protection against myocardial ischemia. To examine these pathways we measured the activation and translocation of protein kinases in hearts from human infants with cyanotic (SaO2<85%) and acyanotic (SaO2'<95%) heart defects and in hearts from infant rabbits raised from birth in a hypoxic and normoxic environment. We then determined the contribution of protein kinases to cardioprotection in chronically hypoxic and normoxic infant rabbit hearts.

In both the chronically hypoxic human infant and rabbit hearts there was activation of PKCS which was evident by translocation of the PKCS isoform from the cytosolic to the particulate fraction. Chronic hypoxia also results in activation and translocation of mitogen activated protein kinase (p38 MAPK) and Jun N terminal kinase (JNK) but not p42/p44 MAPK in both human and rabbit hearts. Phosphorylation and activation of IIsp27 a substrate for p38 MAPK was present in chronically hypoxic infant hearts but not in normoxic hearts. This is the first evidence of activation of protein kinase signaling pathways in human infant hearts in response to the stress of chronic oxygen deprivation.

PKCS inhibition by chelerythrine prevents the activation and the translocation of PKCS and p38 MAPK but not p42/p44 MAPK in chronically hypoxic infant rabbit hearts. p38 MAPK inhibition by SB203580 prevents p38 MAPK activation and translocation but not PKCS and p42/p44 MAPK in chronically hypoxic hearts. In chronically hypoxic rabbit hearts PKCS appears upstream of the p38 MAPK pathway. Perfusion of rabbit hearts prior to ischemia with inhibitors of PKCS, p38 MAPK or JNK completely abolished the cardioprotective effects of chronic hypoxia but had no effect in normoxic hearts.

Our studies have revealed that human and rabbit hearts adapt to chronic hypoxia by activation of PKCS, p38 MAPK and JNK signal transduction pathways. These pathways are responsible for cardioprotection in the infant rabbit heart. Exploitation of one or more of these protein kinase signaling pathways may improve cardioprotection in infants and children undergoing repair of congenital heart defects.

Amplatzer Device Now Used to Close Atrial Septal Defects

Beth Newbury Whitstone, RN, MA, clinical research coordinator, Children's Hospital of Wisconsin, and
Andrew Pelech, MD, director, Cardiac Catheterization Lab, Children's Hospital of Wisconsin; associate professor, Pediatrics, Medical College of Wisconsin.

Editor's note: An overview of the amplatzer device titled "Transcatheter Closure of ASDs - The Amplatzer Device" appeared in the October 1998 issue of Heart Matters.

Recently, the FDA approved the investigational use of several devices for ASD closure in the catheterization lab at Children's Hospital of Wisconsin. These devices include the Amplatzer® and the CardioSEAL® septal occuluders.

Stuart Berger, MD, Joseph Cava, MD, Raymond Fedderly, MD, and Andrew Pelech, MD, of the Heart Center at Children's Hospital, have successfully implanted several of these devices in recent months in the cath lab, eliminating the need for surgery in those patients. These physicians also have travelled to area hospitals to place devices in adults with unrepaired ASDs. Children's Hospital of Wisconsin was involved in the surgical arm of this study in October 1998 and was approved over the summer for use of both devices in this clinical trial.

In order to implant a device, a catheter is placed in the femoral vein and, with the help of transesophageal echo and fluoroscopy, the device is threaded through the catheter and positioned to occlude the ASD. Once proper position has been confirmed, the device is deployed and the catheter is withdrawn. This procedure is performed under general anesthesia.

After the device is placed, care includes routine post-catheterization monitoring, several hours of bed rest and frequent checks of the insertion site for signs of bleeding. Patients are allowed to return home at the end of the day if they live locally or the next day if they live out of the area. Anticoagulation therapy with aspirin is required for about six months, until tissue has grown completely over the device.

Defects most amenable to transcatheter closure are secundum ASDs - those located in the central part of the septum. Defects smaller than 20 to 25 mm have the greatest chance for complete closure. The risks of transcatheter ASD closure are less than those associated with operative repair and the complication rate is less than 5 percent.

Adult Congenital Heart Association Provides Support and Education

Alexis Sullivan, RN, Pediatric Intensive Care Unit, Children's Hospital of Wisconsin

Thanks to research, new surgical and non-surgical procedures, medications and better post-operative care, many children born with congenital heart defects (CHD) are living longer, healthier lives and living into adulthood. A non-profit organization, the Adult Congenital Heart Association (ACHA), is available for support and education.

The ACHA educates the public, adults with CHD and the medical community about congenital heart issues through forums, support groups, a newsletter, and their Internet site at www.achaheart.org.

Their quarterly newsletter, The Laurel Wreath, is available online at www.achaheart.org/newsletter or in print. Copies can be requested through the website or by contacting the Adult Congenital Heart Association, attention Mary Kay Klein at 273 Perham St., West Roxbury, MA 02132, (617) 325-1191, email info@achaheart.org

New Director of Cardiothoracic Surgery Announced

James Tweddell, MD, succeeded S. Bert Litwin as director of cardiothoracic surgery Jan. 1.

Tweddell also is an associate professor of Surgery at the Medical College of Wisconsin. He received his medical degree from the University of Cincinnati, College of Medicine in 1985 and completed fellowships in thoracic and cardiovascular surgery at Washington University Medical School Center in St. Louis and in pediatric thoracic and cardiovascular surgery at St. Louis Children's Hospital.

He joined Children's Hospital and the Medical College of Wisconsin in 1994.

Litwin, who began the cardiovascular surgery program at Children's Hospital in 1972, continues an active surgical and consultative practice at Children's Hospital.