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The use of aprotinin for patients undergoing coronary artery bypass graft procedures
JANUARY 1996, VOL 63, NO 1 PERIOPERATIVE PHARMACOLOGY
The use of aprotinin for
patients undergoing coronary artery bypass graft procedures
A
major concern in coronary artery bypass graft (CABG) procedures is the control of intraoperative and postoperative patient blood loss. The US Food and Drug Administration has approved the use of a hemostatic agent (ie, aprotinin [Trasylol]) that reduces the need for blood transfusions in most patients undergoing CABG procedures.' Clinical trials demonstrate that intraoperative administration of aprotinin can alleviate the need for blood transfusions during CABG procedures, which reduces the possibility of transfusion reactions and the transmission of bloodborne pathogens (eg, hepatitis, HIV). Aprotinin also offers a treatment option to patients whose religious beliefs prevent them from receiving blood products.
THERAPEUTIC USE OF APROTlNlN In the 1930s, researchers discovered that aprotinin acted as a protease inactivator in bovine lymph nodes and as a trypsin inhibitor in bovine pancreas glands? Physicians applied this knowledge to introduce aprotinin into clinical use in 1958 for the treatment of acute pancreatitis.RSince the 1950s, aprotinin has been used to treat a number of conditions including w pancreatitis, m shock syndromes, and hyperfibrinolytic hem~rrhage.~ Aprotinin also has been used for patients undergoing liver transplantations and for patients experiencing acute hem~rrhage.~ There
are ongoing studies to determine the efficacy and safety of administering aprotinin to pediatric patients.6 Researchers first studied the effects of aprotinin in patients undergoing CABG procedures in 1987. They demonstrated that aprotinin reduced blood loss and transfusion requirements when it was administered before and during cardiopulmonary bypass (CPB)? More recent studies of patients undergoing CABG procedures have compared patients treated with aprotinin to untreated patients. These researchers discovered that high dosages of aprotinin administered to patients during CABG procedures reduced the amount of banked blood given postoperatively. Patients enrolled in these studies received the same anesthetic agents, underwent the same perfusion techniques, and had the same surgical team members performing the CABG procedures at each clinical research site. Hemoglobin levels in both patient groups decreased by a similar amount during the first 24 hours after surgery. By postoperative day seven, however, hemoglobin levels had increased in both REGINA T. WHITENER, RN, BSN, is a research nurse level I l l , anesthesiology department, University of Texas Health Science Center. San Antonio. VIRGINIA 1. DOYAL, PHARMD,is a research pharmacist, South Texas VeteransHealth Care System, Audie L. Murphy Division, San Antonio.
229 AORN JOURNAL
patient groups and were slightly higher in aprotinin-treated patient groups. Platelet counts fell in both patient groups after the initiation of CPB. This was attributed to a decrease in the number of red blood cells after patient blood levels were diluted with crystalloid priming fluids. There was a further decrease in platelet counts after the administration of protamine, after which the platelet counts in both patient groups increased similarly in both patient group^.^ Preoperative bleeding times did not differ significantly between the two patient groups, and there were no excessive, prolonged bleeding times in either group. Postoperative measurements, however, were significantly different, with prolonged bleeding times in untreated patient groups versus a nonsignificant increase in bleeding times with aprotinin-treated patient groups. In addition, an increase in urine output during the intraoperative period and the first six hours after surgery was noted in aprotinintreated patient groups.
PHARMACOLOGY Aprotinin is a natural protease inhibitor derived from bovine lung. It has a variety of effects on coagulation (eg, inhibits the contact-phase activation of coagulation, decreases bleeding and turnover of coagulation factor^).^ The precise action of aprotinin is unclear; however, it inhibits proteases, such as kallikreins and plasmin,
JANUARY 1996, VOL 63, NO 1
that have a direct effect on fibrinolysis. Aprotinin also preserves the adhesive glycoproteins in platelet membranes and makes them resistant to damage from mechanical injury and high plasmin levels that occur when patients are placed on CPB.l0 Kallikreins. Kallikreins are inactive proteolytic enzymes present in tissue and blood. They can be activated when the patient's blood comes in contact with the CPB circuit. When kallikreins are activated, they release kinins (ie, small polypeptides) that are converted to bradykinin (ie, a powerful arteriolar dilator that increases capillary permeability). Acting as a protease inhibitor, aprotinin prevents the activation of kallikrein enzymes. This activity is measured in kallikrein inhibitor units (KIU). One KIU is the amount of aprotinin necessary to decrease the activity of two biological kallikrein units by 50%.11 Excretion. Aprotinin is accumulated primarily in the kidneys, where it is filtered by the glomeruli and is resorbed actively by the proximal tubules and stored in phagolysosomes. Aprotinin is metabolized slowly by the lysosomal enzymes. The physiological renal handling of aprotinin is similar to that of other small proteins such as insulin. Aprotinin has a plasma half-life of 150 minutes and an elimination half-life of 10 hours.I2
DOSAGE, ADMINISTRATION, AND MEDICATION INTERACTIONS Aprotinin is supplied in 100mL and 200-mL vials as a clear solution containing 10,000 KIU/mL (ie, concentration of 1.4 mg/mL). It is stable when stored in sealed vials at temperatures of 36" F to 77" F (2" C to 25" C)." All IV doses of aprotinin should
Table 1 GLOSSARY
OF PHARMACOLOGY TERMINOLOGY'
Glycopfofeins.Conjugated proteins that upon decomposition yield a protein and a carbohydrate. Half-life. The time required for half the amount of a medication introduced into an organism to be metabolized or excreted. Lysosomul enzymes. Glycoprotein hydrolytic enzymes in the kidney and liver that digest exogenous material (eg, bacteria, organelles of body cells). Phugolysosomes.Bodies formed by the union of ingested particles with lysosomal enzymes. Phumucokinetics. The movement of medications within biological systems that are affected by uptake, distribution, binding, elimination, biotransformation, and rate of movement.
Plasmin. A proteolytic enzyme present in plasma that is responsible for the digestion and lysis of fibrin clots. Profeulytic enzyme (ie, protease). An enzyme that digests proteins. NOTE 1 . Blukiston's Gould Medical Dictionary, fourth ed (New York: McGraw-Hill Book Co, 1979); Stedmun's Medical Dicfionury, 25th ed (Baltimore: Williams & Wilkins, 1990).
be administered through a central venous access line, and no other medications should be administered through that line. Administration of aprotinin. Administration of aprotinin usually follows a regimen that begins with a 1-mL. test dose, followed by a 200-mL loading dose and a constant infusion dose of 50 mL/hr. The patient is observed closely for 10 minutes after the administration of the test dose for symptoms of an allergic reaction or anaphylaxis. If no allergic reaction is evident, general anesthesia is induced in the patient while the loading dose of 200 mL (ie, 2,000,000 KIU) is given slowly during a 20- to 30-minute period. When the loading dose has been administered, the surgeon performs the stemotomy. Before CPB is initiated, the perfusionkt primes the CPB circuit with 200 mL of aprotinin. The anesthesia 230 AORN JOURNAL
care provider administers a continuous IV infusion of 50 mL/hr (ie, 500,000 KIU/hr) throughout the procedure, discontinuing the aprotinin infusion when the surgeon closes the patient's chest.I4 Interactions. Aprotinin is incompatible in vitro with corticosteroids, heparin, tetracyclines, and certain nutrient solutions containing amino acids or fat emulsion. Some studies have indicated a tendency for precipitates to form when aprotinin is administered in the same IV line with heparin. If aprotinin is to be given concomitantly with another medication, each medication should be administered separately through different central venous access IV lines or catheters.I5
POSSIBLE AD VERSE REACTIONS Clinical research data analyzed to date indicate that aprotinin is well tolerated by patients. All
JANUARY 1996, VOL 63, NO I
perioperative nurses, however, must be aware of possible adverse reactions to aprotinin.
Hypersensitivity reactions.
aprotinin-treated patient groups. The incidence of serum creatinine elevations of greater than 0.5 mg/dL above baseline was 20% in aprotinin-treated patient groups, compared to 13% in nontreated patient groups. In the
Hypersensitivity reactions reported with use of aprotinin range from skin eruptions, itching, dyspnea, and nausea to tachycardia and anaphylactic shock with circulatory failure. Anaphylaxis has occurred in less than 0.5% of patients during worldwide clinical use of aprotinin. It most often occurs in patients who have had previous exposure to the medication. When a hypersensitivity reaction does occur, the anesthesia care provider stops the administration of aprotinin immediately and initiates emergency treatment with antihistamines and steroids. The anesthesia care provider uses extreme caution when treating a patient majority of patients, the postoperwith known exposure to aproative renal dysfunction was not tinin by administering antihistasevere and was reversible, and mines to the patient before giving the rise in serum creatinine levels the test dose of aprotinin.I6 was transient.18Although no formal studies of the pharmacokinetOther side effects. Other side ics of aprotinin in patients with effects observed with the use of aprotinin have been atrial fibrillapreexisting renal insufficiency tion, ventricular tachycardia, and have been conducted, patients premature ventricular arrhythmias, with baseline elevations in serum which are frequent sequelae of creatinine did not demonstrate increased risk of developing postCABG procedures and are not attributable necessarily to aprooperative renal dysfunction after tinin therapy. Less frequent adreceiving aprotinin. I9 verse events noted in patients In the initial hours after CABG treated with aprotinin were procedures, serum glucose levels phlebitis (1.4%), kidney tubular in aprotinin-treated patient groups necrosis (1.4%). convulsion increased, but this trend was tran(0.8%),cerebral embolism (0.8%), sient.*"In addition, partial thromliver damage (0.5%),acute kidney boplastin times and activated clotfailure (0.5%),cerebrovascular ting times were elevated signifiaccident (0.5%),lung edema cantly in aprotinin-treated patient (0.5%),and hemolysis (0.5?41).'~ groups during the first hours after laboratory findings. Data CABG procedures because of cirfrom three clinical studies culating concentrations of aproshowed a statistically significant tinin, which are known to inhibit increase in the incidence of postthe activation of the intrinsic clotoperative renal dysfunction in ting mechanism.21
Patients are observed closely for hypersensitivity reactions after the administration of aprotinin.
231 AORN JOURNAL
PERIOPERATIVE NURSING CONSIDERATIONS Patients who receive aprotinin or blood transfusions during the perioperative period present unique challenges to perioperative nurses. Transfusion reactions. Blood transfusions given during CABG procedures frequently are administered while patients are on CPB. During this time, anesthesia care providers and perfusionists control patients' oxygenation levels and perfusion rates by artificial means, and circulating nurses maintain patients in hypothermic states during graft placements. The only indicators that might alert surgical team members to transfusion reactions are changes in patients' serial laboratory test results (eg, hemoglobin, hematocrit, electrolytes, blood gas values). Treatment of blood transfusion reactions and hypersensitivity reactions to aprotinin is the same: stop the blood transfusion or the aprotinin infusion and administer antihistamines and other medications as appropriate.
Aprotinin administration. Aprotinin is contraindicated in patients who are hypersensitive to beef because the medication is derived from bovine lung. In addition, patients with allergies to medications or other substances may be at higher risk for developing hypersensitivity reactions to aprotinin. Perioperative team members should administer all aprotinin doses through central venous access IV lines and use separate IV lines to administer other medications. Penoperative nurses should observe patients receiving aprotinin closely for hypersensitivity reactions after administration of test doses. Test doses are particularly important for patients who
JANUARY 1996, VOL 63, NO 1
have received aprotinin previously because they have a higher risk of anaphylaxis. In such patients, pretreatment with an antihistamine is recommended. Patients may experience anaphylaxis after full therapeutic doses even if they remained asymptomatic after test doses. If symptoms of hypersensitivity reactions occur, surgical team members should discontinue the IV infusion of aprotinin and administer appropriate supportive treatments (eg, antihistamines, vasopressors, corticosteroids).
Monitoring laboratory test results. Perioperative nurses should monitor patients for increased serum creatinine levels and other signs of nephrotoxicity. If nephrotoxicity occurs, however, it usually is mild and reversible. Aprotinin increases levels for
activated clotting times and partial thromboplastin times. Nurses should monitor these laboratory test results, along with patients’ blood losses and urinary outputs, during the perioperative period. Postoperative nurses should obtain laboratory test results on the previously mentioned blood levels after surgery and compare them to patients’ preoperative laboratory test results. These same indicators should be monitored closely while patients are in postanesthesia care units and should continue when patients are transferred to other postoperative care units and throughout their hospitalizations.
SUMMARY Using aprotinin may alleviate patients’ fears of receiving bloodborne pathogens through blood products and may decrease the
NOTES 1. “FDA-approved new drug bulletin,” RN 57 (September 1994) 31-32. 2. H Fritz and G Wunderer, “Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs,” Arzneimittelforschung 33 (April 1983) 479-494; M Verstraete, “Clinical application of inhibitors of fibrinolysis,” Drugs 29 (March 1985) 236-261. 3. J E Trapnell et al, “A controlled trial of Trasylol in the treatment of acute pancreatitis,” British Journal of Surgery 61 (March 1974) 177-182. 4. Verstraete, “Clinical application of inhibitors of fib rinolysis,” 236-261; D A Tice et al, “The inhibition of Trasylol on fibrinolytic activity associated with cardiovascular operations,” Surgery, Gynecology and Obstetrics 120 (July 1964) 71-74; T W Feeley, L A Rinsky, “Use of aprotinin to reduce intraoperative bleeding,” The Western Journal of Medicine 159 (August 1993) 189-192. 5. G M Patrassi et al, “Aprotinin efficacy on intraoperative bleeding and transfusion requirements in orthotopic liver transplantation,” Transfusion 34 (June 1994) 50751 1; S Valentine, P Williamson, D Sutton, “Reduction of acute haemorrhage with apiotinin,” Anaesthesia 48 (May 1993) 405-406. 6. J Boldt et al, “Comparison of two aprotinin dosage regimens in pediatric patients having cardiac operations,” Journal of Thoracic and CardiovascularSurgery 105 (April 1993) 705-71 1; W Dietrich et al, “Hemostatic acti-
necessity of transfusions of blood and blood products during CABG procedures. Members of religious groups whose beliefs forbid them from receiving blood and blood products now have the option of receiving aprotinin during CABG procedures. A recent study estimated the cost of transfusing one unit of packed red blood cells as approximately $120.22This cost does not reflect the cost of nursing care to administer the blood or the cost of added medical care in cases of transfusion reactions or transfusion-acquired, bloodbome diseases. Aprotinin costs approximately $900 per high-dosage treatment.23 If using aprotinin limits the use of blood products, however, the cost of aprotinin is offset through decreased costs of CABG procedures that do not require blood transfusions. A
vation during cardiopulmonary bypass with different aprotinim dosages in pediatric patients having cardiac operations,” Journal of Thoracic and Cardiovascular Surgery 105 (April 1993) 712-720. 7. D Royston et al, “Effect of aprotinin on the need for blood transfusions after repeat open-heart surgery,” Lancet 2 (December 1987) 1289-1291. 8. B P Bidstrup et al, “Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin (Trasylol),”Journal of Thoracic and Cardiovascular Surgery 97 (March 1989) 364-372; W Dietrich et al, “Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization,” Anesthesiology 73 (December 1990) 1119-1126; W van Oeveren et al, “Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass,” Annals of Thoracic Surgery 44 (December 1987) 640-645. 9. PDR Generics, ed P R Ajmera et al (Montvale, NJ: Medical Economics, 1995) 196-198. 10. B Blauhut et al, “Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis complement, and renal function after cardiopulmonary bypass,” Journal of Thoracic and Cardiovascular Surgery 101 (June 1991) 958-967; J Lavee et al, “Platelet protection by low-dose aprotinin in cardiopulmonary bypass: Electron microscopic study,”Annals of Thoracic Surgety 55 (January 1993) 114-119; J H Levy, J M Bailey, M
232 AORN JOURNAL
JANUARY 1996, VOL 63, NO 1
Salmenpera, “Pharmacokinetics of aprotinin in preoperative cardiac surgical patients,”Anesthesiology 80 (May 1994) 1013-1018. 1 1. A C Guyton, “Local control of blood flow by the tissues and humoral regulation,” in Textbook of Medical Physiology, eighth ed (Philadelphia: W B Saunders Co, 1990) 191-192; Levy,Bailey, Salmenpera, “Pharmacokinetics of aprotinin in preoperative cardiac surgical patients,” 1013-1018. 12. G K McEvoy, ed, American Hospital Formulary
16. Ibid. 17. Ibid. 18. Levy, Bailey, Salmenpera, “Pharmacokinetics of aprotinin in preoperative cardiac surgical patients,” 10131018; PDR Generics, 198. 19. Blauhut et al, “Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis complement, and renal function after cardiopulmonary bypass,” 958-967. 20. McEvoy, ed, American Hospital Formulary Service
Service Drug Information Current Developments, Supplement A (Bethesda, Md: American Society of Hospital
3-5. 2 1. Ibid. 22. D A Lubarsky et al, “The hospital cost (fiscal year 1991/1992) of a simple perioperative allogeneic red blood cell transfusion during elective surgery at Duke University,” Anesthesia and Analgesia 79 (October 1994) 629637. 23. R T Whitener, personal communication with pharmaceutical sales specialist from Miles, Inc, San Antonio, 21 March 1995.
Pharmacists, 1994) 3-5. 13. Ibid. 14. “Miles introduces agent for reducing blood transfusion requirements,” (News)American Journal of Hospital Pharmacy 51 (June 1994) 1387. 15. McEvoy, ed, American Hospital Formulary Service Drug Information Current Developments, Supplement A, 3-5; PDR Generics, 198.
Drug Informution Current Developments, Supplement A,
Shuttle Bus Information for Congress Attendees who wear Congress badges may ride AORN shuttle buses from Saturday, March 2, through Friday, March 8,1995, at no charge. Information about bus routes and schedules will
be available at registration counters at the Dallas Convention Center and at all official Congress hotels. Bus service will not be provided for meetings arranged by states, chapters, or other groups.
New Program for Allied ProfessionalsAttending Congress Recognizing the increased involvement of allied professionals in perioperative patient care, AORN is inviting purchasing agents, materials managers, and health facility financial officers to participate in Congress. In addition to visiting the exhibits, these professionals will be interested in many education sessions at Congress. Following are some of the sessions of particular interest to allied professionals. “Making Tough Choices in Challenging Times” “Pioneer Spirit: Exploring New Frontiers in Perioperative Practice” “Surfing the Information Superhighway: Information & Implications for OR Nurses” “Pitfalls in Reuse Recommendations: An Analysis of Legal & Regulatory Issues Confronting Industry & Hospitals” “Antibiotic Resistance: An Emerging Public Health Threat & Perioperative Nursing Challenge” “Infectious Hazards of the Anesthesia Workplace
to Patients and Staff’ “Life Would Be Easy if it Weren’t for Other People” “Changing Minds for Changing Times” “Importing the Culture of the Ambulatory Surgery Center into Hospital-Based Surgery Services” “Sterilization-Murder in the 10th: Are You Getting the Job Done?’ “Pearl & Edith Take A Trip Over the Falls: Changing Victim & Entitlement Mind-sets to Adjust to the New Workplaces” “Improving Organizational Performance: A Workshop for Implementing Case Management” “Windows of Opportunity: Perioperative Opportunities in Home Health” “The Care and Feeding of a Successful Attitude” The daily registration fee for allied professionals is $1 25; multiple-day registration is $250. 234
AORN JOURNAL
The use of aprotinin for
patients undergoing coronary artery bypass graft procedures
A
major concern in coronary artery bypass graft (CABG) procedures is the control of intraoperative and postoperative patient blood loss. The US Food and Drug Administration has approved the use of a hemostatic agent (ie, aprotinin [Trasylol]) that reduces the need for blood transfusions in most patients undergoing CABG procedures.' Clinical trials demonstrate that intraoperative administration of aprotinin can alleviate the need for blood transfusions during CABG procedures, which reduces the possibility of transfusion reactions and the transmission of bloodborne pathogens (eg, hepatitis, HIV). Aprotinin also offers a treatment option to patients whose religious beliefs prevent them from receiving blood products.
THERAPEUTIC USE OF APROTlNlN In the 1930s, researchers discovered that aprotinin acted as a protease inactivator in bovine lymph nodes and as a trypsin inhibitor in bovine pancreas glands? Physicians applied this knowledge to introduce aprotinin into clinical use in 1958 for the treatment of acute pancreatitis.RSince the 1950s, aprotinin has been used to treat a number of conditions including w pancreatitis, m shock syndromes, and hyperfibrinolytic hem~rrhage.~ Aprotinin also has been used for patients undergoing liver transplantations and for patients experiencing acute hem~rrhage.~ There
are ongoing studies to determine the efficacy and safety of administering aprotinin to pediatric patients.6 Researchers first studied the effects of aprotinin in patients undergoing CABG procedures in 1987. They demonstrated that aprotinin reduced blood loss and transfusion requirements when it was administered before and during cardiopulmonary bypass (CPB)? More recent studies of patients undergoing CABG procedures have compared patients treated with aprotinin to untreated patients. These researchers discovered that high dosages of aprotinin administered to patients during CABG procedures reduced the amount of banked blood given postoperatively. Patients enrolled in these studies received the same anesthetic agents, underwent the same perfusion techniques, and had the same surgical team members performing the CABG procedures at each clinical research site. Hemoglobin levels in both patient groups decreased by a similar amount during the first 24 hours after surgery. By postoperative day seven, however, hemoglobin levels had increased in both REGINA T. WHITENER, RN, BSN, is a research nurse level I l l , anesthesiology department, University of Texas Health Science Center. San Antonio. VIRGINIA 1. DOYAL, PHARMD,is a research pharmacist, South Texas VeteransHealth Care System, Audie L. Murphy Division, San Antonio.
229 AORN JOURNAL
patient groups and were slightly higher in aprotinin-treated patient groups. Platelet counts fell in both patient groups after the initiation of CPB. This was attributed to a decrease in the number of red blood cells after patient blood levels were diluted with crystalloid priming fluids. There was a further decrease in platelet counts after the administration of protamine, after which the platelet counts in both patient groups increased similarly in both patient group^.^ Preoperative bleeding times did not differ significantly between the two patient groups, and there were no excessive, prolonged bleeding times in either group. Postoperative measurements, however, were significantly different, with prolonged bleeding times in untreated patient groups versus a nonsignificant increase in bleeding times with aprotinin-treated patient groups. In addition, an increase in urine output during the intraoperative period and the first six hours after surgery was noted in aprotinintreated patient groups.
PHARMACOLOGY Aprotinin is a natural protease inhibitor derived from bovine lung. It has a variety of effects on coagulation (eg, inhibits the contact-phase activation of coagulation, decreases bleeding and turnover of coagulation factor^).^ The precise action of aprotinin is unclear; however, it inhibits proteases, such as kallikreins and plasmin,
JANUARY 1996, VOL 63, NO 1
that have a direct effect on fibrinolysis. Aprotinin also preserves the adhesive glycoproteins in platelet membranes and makes them resistant to damage from mechanical injury and high plasmin levels that occur when patients are placed on CPB.l0 Kallikreins. Kallikreins are inactive proteolytic enzymes present in tissue and blood. They can be activated when the patient's blood comes in contact with the CPB circuit. When kallikreins are activated, they release kinins (ie, small polypeptides) that are converted to bradykinin (ie, a powerful arteriolar dilator that increases capillary permeability). Acting as a protease inhibitor, aprotinin prevents the activation of kallikrein enzymes. This activity is measured in kallikrein inhibitor units (KIU). One KIU is the amount of aprotinin necessary to decrease the activity of two biological kallikrein units by 50%.11 Excretion. Aprotinin is accumulated primarily in the kidneys, where it is filtered by the glomeruli and is resorbed actively by the proximal tubules and stored in phagolysosomes. Aprotinin is metabolized slowly by the lysosomal enzymes. The physiological renal handling of aprotinin is similar to that of other small proteins such as insulin. Aprotinin has a plasma half-life of 150 minutes and an elimination half-life of 10 hours.I2
DOSAGE, ADMINISTRATION, AND MEDICATION INTERACTIONS Aprotinin is supplied in 100mL and 200-mL vials as a clear solution containing 10,000 KIU/mL (ie, concentration of 1.4 mg/mL). It is stable when stored in sealed vials at temperatures of 36" F to 77" F (2" C to 25" C)." All IV doses of aprotinin should
Table 1 GLOSSARY
OF PHARMACOLOGY TERMINOLOGY'
Glycopfofeins.Conjugated proteins that upon decomposition yield a protein and a carbohydrate. Half-life. The time required for half the amount of a medication introduced into an organism to be metabolized or excreted. Lysosomul enzymes. Glycoprotein hydrolytic enzymes in the kidney and liver that digest exogenous material (eg, bacteria, organelles of body cells). Phugolysosomes.Bodies formed by the union of ingested particles with lysosomal enzymes. Phumucokinetics. The movement of medications within biological systems that are affected by uptake, distribution, binding, elimination, biotransformation, and rate of movement.
Plasmin. A proteolytic enzyme present in plasma that is responsible for the digestion and lysis of fibrin clots. Profeulytic enzyme (ie, protease). An enzyme that digests proteins. NOTE 1 . Blukiston's Gould Medical Dictionary, fourth ed (New York: McGraw-Hill Book Co, 1979); Stedmun's Medical Dicfionury, 25th ed (Baltimore: Williams & Wilkins, 1990).
be administered through a central venous access line, and no other medications should be administered through that line. Administration of aprotinin. Administration of aprotinin usually follows a regimen that begins with a 1-mL. test dose, followed by a 200-mL loading dose and a constant infusion dose of 50 mL/hr. The patient is observed closely for 10 minutes after the administration of the test dose for symptoms of an allergic reaction or anaphylaxis. If no allergic reaction is evident, general anesthesia is induced in the patient while the loading dose of 200 mL (ie, 2,000,000 KIU) is given slowly during a 20- to 30-minute period. When the loading dose has been administered, the surgeon performs the stemotomy. Before CPB is initiated, the perfusionkt primes the CPB circuit with 200 mL of aprotinin. The anesthesia 230 AORN JOURNAL
care provider administers a continuous IV infusion of 50 mL/hr (ie, 500,000 KIU/hr) throughout the procedure, discontinuing the aprotinin infusion when the surgeon closes the patient's chest.I4 Interactions. Aprotinin is incompatible in vitro with corticosteroids, heparin, tetracyclines, and certain nutrient solutions containing amino acids or fat emulsion. Some studies have indicated a tendency for precipitates to form when aprotinin is administered in the same IV line with heparin. If aprotinin is to be given concomitantly with another medication, each medication should be administered separately through different central venous access IV lines or catheters.I5
POSSIBLE AD VERSE REACTIONS Clinical research data analyzed to date indicate that aprotinin is well tolerated by patients. All
JANUARY 1996, VOL 63, NO I
perioperative nurses, however, must be aware of possible adverse reactions to aprotinin.
Hypersensitivity reactions.
aprotinin-treated patient groups. The incidence of serum creatinine elevations of greater than 0.5 mg/dL above baseline was 20% in aprotinin-treated patient groups, compared to 13% in nontreated patient groups. In the
Hypersensitivity reactions reported with use of aprotinin range from skin eruptions, itching, dyspnea, and nausea to tachycardia and anaphylactic shock with circulatory failure. Anaphylaxis has occurred in less than 0.5% of patients during worldwide clinical use of aprotinin. It most often occurs in patients who have had previous exposure to the medication. When a hypersensitivity reaction does occur, the anesthesia care provider stops the administration of aprotinin immediately and initiates emergency treatment with antihistamines and steroids. The anesthesia care provider uses extreme caution when treating a patient majority of patients, the postoperwith known exposure to aproative renal dysfunction was not tinin by administering antihistasevere and was reversible, and mines to the patient before giving the rise in serum creatinine levels the test dose of aprotinin.I6 was transient.18Although no formal studies of the pharmacokinetOther side effects. Other side ics of aprotinin in patients with effects observed with the use of aprotinin have been atrial fibrillapreexisting renal insufficiency tion, ventricular tachycardia, and have been conducted, patients premature ventricular arrhythmias, with baseline elevations in serum which are frequent sequelae of creatinine did not demonstrate increased risk of developing postCABG procedures and are not attributable necessarily to aprooperative renal dysfunction after tinin therapy. Less frequent adreceiving aprotinin. I9 verse events noted in patients In the initial hours after CABG treated with aprotinin were procedures, serum glucose levels phlebitis (1.4%), kidney tubular in aprotinin-treated patient groups necrosis (1.4%). convulsion increased, but this trend was tran(0.8%),cerebral embolism (0.8%), sient.*"In addition, partial thromliver damage (0.5%),acute kidney boplastin times and activated clotfailure (0.5%),cerebrovascular ting times were elevated signifiaccident (0.5%),lung edema cantly in aprotinin-treated patient (0.5%),and hemolysis (0.5?41).'~ groups during the first hours after laboratory findings. Data CABG procedures because of cirfrom three clinical studies culating concentrations of aproshowed a statistically significant tinin, which are known to inhibit increase in the incidence of postthe activation of the intrinsic clotoperative renal dysfunction in ting mechanism.21
Patients are observed closely for hypersensitivity reactions after the administration of aprotinin.
231 AORN JOURNAL
PERIOPERATIVE NURSING CONSIDERATIONS Patients who receive aprotinin or blood transfusions during the perioperative period present unique challenges to perioperative nurses. Transfusion reactions. Blood transfusions given during CABG procedures frequently are administered while patients are on CPB. During this time, anesthesia care providers and perfusionists control patients' oxygenation levels and perfusion rates by artificial means, and circulating nurses maintain patients in hypothermic states during graft placements. The only indicators that might alert surgical team members to transfusion reactions are changes in patients' serial laboratory test results (eg, hemoglobin, hematocrit, electrolytes, blood gas values). Treatment of blood transfusion reactions and hypersensitivity reactions to aprotinin is the same: stop the blood transfusion or the aprotinin infusion and administer antihistamines and other medications as appropriate.
Aprotinin administration. Aprotinin is contraindicated in patients who are hypersensitive to beef because the medication is derived from bovine lung. In addition, patients with allergies to medications or other substances may be at higher risk for developing hypersensitivity reactions to aprotinin. Perioperative team members should administer all aprotinin doses through central venous access IV lines and use separate IV lines to administer other medications. Penoperative nurses should observe patients receiving aprotinin closely for hypersensitivity reactions after administration of test doses. Test doses are particularly important for patients who
JANUARY 1996, VOL 63, NO 1
have received aprotinin previously because they have a higher risk of anaphylaxis. In such patients, pretreatment with an antihistamine is recommended. Patients may experience anaphylaxis after full therapeutic doses even if they remained asymptomatic after test doses. If symptoms of hypersensitivity reactions occur, surgical team members should discontinue the IV infusion of aprotinin and administer appropriate supportive treatments (eg, antihistamines, vasopressors, corticosteroids).
Monitoring laboratory test results. Perioperative nurses should monitor patients for increased serum creatinine levels and other signs of nephrotoxicity. If nephrotoxicity occurs, however, it usually is mild and reversible. Aprotinin increases levels for
activated clotting times and partial thromboplastin times. Nurses should monitor these laboratory test results, along with patients’ blood losses and urinary outputs, during the perioperative period. Postoperative nurses should obtain laboratory test results on the previously mentioned blood levels after surgery and compare them to patients’ preoperative laboratory test results. These same indicators should be monitored closely while patients are in postanesthesia care units and should continue when patients are transferred to other postoperative care units and throughout their hospitalizations.
SUMMARY Using aprotinin may alleviate patients’ fears of receiving bloodborne pathogens through blood products and may decrease the
NOTES 1. “FDA-approved new drug bulletin,” RN 57 (September 1994) 31-32. 2. H Fritz and G Wunderer, “Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs,” Arzneimittelforschung 33 (April 1983) 479-494; M Verstraete, “Clinical application of inhibitors of fibrinolysis,” Drugs 29 (March 1985) 236-261. 3. J E Trapnell et al, “A controlled trial of Trasylol in the treatment of acute pancreatitis,” British Journal of Surgery 61 (March 1974) 177-182. 4. Verstraete, “Clinical application of inhibitors of fib rinolysis,” 236-261; D A Tice et al, “The inhibition of Trasylol on fibrinolytic activity associated with cardiovascular operations,” Surgery, Gynecology and Obstetrics 120 (July 1964) 71-74; T W Feeley, L A Rinsky, “Use of aprotinin to reduce intraoperative bleeding,” The Western Journal of Medicine 159 (August 1993) 189-192. 5. G M Patrassi et al, “Aprotinin efficacy on intraoperative bleeding and transfusion requirements in orthotopic liver transplantation,” Transfusion 34 (June 1994) 50751 1; S Valentine, P Williamson, D Sutton, “Reduction of acute haemorrhage with apiotinin,” Anaesthesia 48 (May 1993) 405-406. 6. J Boldt et al, “Comparison of two aprotinin dosage regimens in pediatric patients having cardiac operations,” Journal of Thoracic and CardiovascularSurgery 105 (April 1993) 705-71 1; W Dietrich et al, “Hemostatic acti-
necessity of transfusions of blood and blood products during CABG procedures. Members of religious groups whose beliefs forbid them from receiving blood and blood products now have the option of receiving aprotinin during CABG procedures. A recent study estimated the cost of transfusing one unit of packed red blood cells as approximately $120.22This cost does not reflect the cost of nursing care to administer the blood or the cost of added medical care in cases of transfusion reactions or transfusion-acquired, bloodbome diseases. Aprotinin costs approximately $900 per high-dosage treatment.23 If using aprotinin limits the use of blood products, however, the cost of aprotinin is offset through decreased costs of CABG procedures that do not require blood transfusions. A
vation during cardiopulmonary bypass with different aprotinim dosages in pediatric patients having cardiac operations,” Journal of Thoracic and Cardiovascular Surgery 105 (April 1993) 712-720. 7. D Royston et al, “Effect of aprotinin on the need for blood transfusions after repeat open-heart surgery,” Lancet 2 (December 1987) 1289-1291. 8. B P Bidstrup et al, “Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin (Trasylol),”Journal of Thoracic and Cardiovascular Surgery 97 (March 1989) 364-372; W Dietrich et al, “Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization,” Anesthesiology 73 (December 1990) 1119-1126; W van Oeveren et al, “Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass,” Annals of Thoracic Surgery 44 (December 1987) 640-645. 9. PDR Generics, ed P R Ajmera et al (Montvale, NJ: Medical Economics, 1995) 196-198. 10. B Blauhut et al, “Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis complement, and renal function after cardiopulmonary bypass,” Journal of Thoracic and Cardiovascular Surgery 101 (June 1991) 958-967; J Lavee et al, “Platelet protection by low-dose aprotinin in cardiopulmonary bypass: Electron microscopic study,”Annals of Thoracic Surgety 55 (January 1993) 114-119; J H Levy, J M Bailey, M
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Salmenpera, “Pharmacokinetics of aprotinin in preoperative cardiac surgical patients,”Anesthesiology 80 (May 1994) 1013-1018. 1 1. A C Guyton, “Local control of blood flow by the tissues and humoral regulation,” in Textbook of Medical Physiology, eighth ed (Philadelphia: W B Saunders Co, 1990) 191-192; Levy,Bailey, Salmenpera, “Pharmacokinetics of aprotinin in preoperative cardiac surgical patients,” 1013-1018. 12. G K McEvoy, ed, American Hospital Formulary
16. Ibid. 17. Ibid. 18. Levy, Bailey, Salmenpera, “Pharmacokinetics of aprotinin in preoperative cardiac surgical patients,” 10131018; PDR Generics, 198. 19. Blauhut et al, “Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis complement, and renal function after cardiopulmonary bypass,” 958-967. 20. McEvoy, ed, American Hospital Formulary Service
Service Drug Information Current Developments, Supplement A (Bethesda, Md: American Society of Hospital
3-5. 2 1. Ibid. 22. D A Lubarsky et al, “The hospital cost (fiscal year 1991/1992) of a simple perioperative allogeneic red blood cell transfusion during elective surgery at Duke University,” Anesthesia and Analgesia 79 (October 1994) 629637. 23. R T Whitener, personal communication with pharmaceutical sales specialist from Miles, Inc, San Antonio, 21 March 1995.
Pharmacists, 1994) 3-5. 13. Ibid. 14. “Miles introduces agent for reducing blood transfusion requirements,” (News)American Journal of Hospital Pharmacy 51 (June 1994) 1387. 15. McEvoy, ed, American Hospital Formulary Service Drug Information Current Developments, Supplement A, 3-5; PDR Generics, 198.
Drug Informution Current Developments, Supplement A,
Shuttle Bus Information for Congress Attendees who wear Congress badges may ride AORN shuttle buses from Saturday, March 2, through Friday, March 8,1995, at no charge. Information about bus routes and schedules will
be available at registration counters at the Dallas Convention Center and at all official Congress hotels. Bus service will not be provided for meetings arranged by states, chapters, or other groups.
New Program for Allied ProfessionalsAttending Congress Recognizing the increased involvement of allied professionals in perioperative patient care, AORN is inviting purchasing agents, materials managers, and health facility financial officers to participate in Congress. In addition to visiting the exhibits, these professionals will be interested in many education sessions at Congress. Following are some of the sessions of particular interest to allied professionals. “Making Tough Choices in Challenging Times” “Pioneer Spirit: Exploring New Frontiers in Perioperative Practice” “Surfing the Information Superhighway: Information & Implications for OR Nurses” “Pitfalls in Reuse Recommendations: An Analysis of Legal & Regulatory Issues Confronting Industry & Hospitals” “Antibiotic Resistance: An Emerging Public Health Threat & Perioperative Nursing Challenge” “Infectious Hazards of the Anesthesia Workplace
to Patients and Staff’ “Life Would Be Easy if it Weren’t for Other People” “Changing Minds for Changing Times” “Importing the Culture of the Ambulatory Surgery Center into Hospital-Based Surgery Services” “Sterilization-Murder in the 10th: Are You Getting the Job Done?’ “Pearl & Edith Take A Trip Over the Falls: Changing Victim & Entitlement Mind-sets to Adjust to the New Workplaces” “Improving Organizational Performance: A Workshop for Implementing Case Management” “Windows of Opportunity: Perioperative Opportunities in Home Health” “The Care and Feeding of a Successful Attitude” The daily registration fee for allied professionals is $1 25; multiple-day registration is $250. 234
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