Anesth Analg 2001;93:1260-1261
© 2001 International Anesthesia Research Society
ANESTHETIC PHARMACOLOGY
A Delayed Cardiopulmonary Reaction to an Intravenous Immunosuppressant Thymoglobulin After Pancreas Transplant
Michael K. Loushin, MD,
Ian K. Hasinoff, MD FRCPC, and
Kumar G. Belani, MBBS MS
Department of Anesthesiology, University of Minnesota, Minneapolis, Minnesota
Address correspondence and reprint requests to Michael K. Loushin, MD, Department of Anesthesiology, University of Minnesota, 420 Delaware Street SE, MMC, Minneapolis, MN 55455. Address e-mail to loush001{at}umn.edu
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Abstract
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IMPLICATIONS:Adverse cardiopulmonary reaction to an intravenous immunosuppressant aftersolid organ transplantation might not be evident immediately in the postoperative period and might result in serious cardiopulmonary compromise.
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Introduction
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The success of solid organ transplantation has been, in part, a result of improvements in immunosuppressant therapy. Unfortunately, the use of potent immunosuppressants is sometimes associated with life-threatening reactions. This case report describes our experience with a patient who possibly developed a severe adverse reaction to an IV immunosuppressant used during a cadaveric pancreas transplant.
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Case Report
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A 60-yr-old Caucasian male (weight, 122.3 kg; height, 190.5 cm) was anesthetized for a cadaveric pancreas transplant procedure. His medical history was significant for the following: insulin-dependant diabetes (over 20 yr), living related kidney transplant (1996), mild renal insufficiency (baseline creatinine 1.5 mg/dL), hypertension, coronary artery disease involving the right coronary artery (stented May 2000) and left circumflex (50%–60% occlusion), myocardial infarction (1992), and normal left ventricular function by echocardiogram (2000). His allergies were to codeine, oxycodone, and propoxyphene napsylate, all producing untoward gastrointestinal symptoms.
Anesthesia was induced with etomidate (40 mg), fentanyl (500 µg), and cisatracurium (20 mg) IV after application of routine intraoperative monitors. A triple-lumen right internal jugular central venous catheter was placed percutaneously without complications. Piperacillin, fluconazole, and methylprednisolone were given IV before induction of anesthesia. Additional immunosuppressive medications, including daclizumab, mycophenolate, and Thymoglobulin (IMTIX-SANGSTAT, Lyon, France) (through a 0.22 micron filter), were infused centrally over 2 h, 3 h, and 6 h, respectively. Graft reperfusion was uneventful, and no intraoperative complications were encountered. After abdominal closure, the patient was transferred to the postanesthesia care unit (PACU) for emergence and tracheal extubation. After full recovery of motor strength and regaining consciousness, he was tracheally extubated. He remained comfortable but tachypneic with a respiratory rate of 24 breaths/min and SpO2 100% while breathing 2 L/min oxygen by nasal cannula. Electrocardiogram (ECG) revealed no changes from the preoperative ECG. Arterial blood pressure, heart rate, and chest radiograph were unremarkable. Postoperative electrolytes were as follows: sodium 139 mmol/L, potassium 4.7 mmol/L, chloride 112 mmol/L, bicarbonate 24 mmol/L, blood urea nitrogen 27 mmol/L, creatinine 1.8 mg/dL, and blood glucose 186 mg/dL. In the PACU, the patient received fentanyl (50 µg) IV and morphine (6 mg) IV in divided doses. After a short stay in the PACU, the patient was transferred to the transplant ward.
Three hours postoperatively, we were called to see the patient for increasing respiratory distress. On examination, his respiratory rate was 36–40 breaths/min, SpO2 98% on 4 L/min oxygen by nasal cannula, and heart rate 105 bpm. He had bilateral wheezing and decreased air movement. Albuterol by inhalation was immediately administered resulting in significant improvement in breathing and comfort (respiratory rate 22 breaths/min, SpO2 100% on 4 L/min oxygen by nasal cannula, heart rate 100 bpm). He was transferred to the surgical intensive care unit for close observation.
Immediately upon arrival to the surgical intensive care unit (4.5 h postoperatively), the patient became hemodynamically unstable. His breathing was very shallow, and he rapidly became unresponsive. His heart rate was 37 bpm and blood pressure was unobtainable. Bedside ECG revealed severe sinus bradycardia. Cardiopulmonary resuscitation (CPR) was immediately initiated. The trachea was intubated with a 9.0-mm endotracheal tube; epinephrine 1 mg IV and atropine 1 mg IV were given. Initial venous blood gas was pH 6.97, PvCO2 72 mm Hg, PvO2 34 mm Hg, and HCO2- 16 mEq/L. After several minutes of CPR, his heart rate was 115 bpm, blood pressure 133/82 mm Hg, and SpO2 99%. Arterial blood gas was pH 7.03, PaCO2 46, PaO2 132, and HCO3- 11. Postevent 12-lead ECG revealed no acute changes; a transthoracic echocardiogram was negative for any new wall motion abnormalities. Troponin-I (normal range, 0–1.9 µg/dL) measurements were 0.1 µg/dL, 0.3 µg/dL, and 3.2 µg/dL at 0 h, 6 h, and 13 h postoperatively, with a peak of 4.5 µg/dL at 21 h. Despite these events, the patient gradually recovered without serious residual organ dysfunction and was transferred back to the transplant ward on postoperative day two. We concluded that the patient encountered a delayed Thymoglobulin reaction. No reactions were noted with subsequent doses of mycophenolate, daclizumab, methylprednisolone, or antibiotics.
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Discussion
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Each year, approximately 1800 pancreas transplants are performed worldwide (1). Advancement in immunosuppressant therapy has contributed to the success of solid organ transplantation. Some of the IV immunosuppressants have side effects that can range from mild to life threatening. Thymoglobulin is a polyclonal antilymphocyte antibody obtained from rabbits that binds to human cell surface receptors, resulting in opsonization of lymphocytes (2,3). It is recommended that Thymoglobulin be infused centrally over 6 hours and through a 0.22-micron filter. Adverse reactions to Thymoglobulin may include fever, chills, dyspnea, tachycardia, hyperkalemia, malaise, thrombocytopenia, and leukopenia (4,5).
At our institution, at least five patients have developed mild to moderate respiratory complications with IV administration of Thymoglobulin. These patients required minimal respiratory support, such as supplemental oxygen and albuterol therapy in the PACU. None required more advanced cardiopulmonary support. However, this is the first case at our institution of severe cardiopulmonary compromise secondary to Thymoglobulin infusion requiring intubation and CPR.
The delayed onset of respiratory complication also makes this case intriguing. In retrospect, tachypnea noted in the PACU may have been a warning of an impending drug-associated reaction. However, tachypnea is not uncommon in the PACU. In this patient, the tachypnea progressed to a severe reaction approximately 7 hours after infusion of Thymoglobulin. Even though all standard precautions for infusion of Thymoglobulin were implemented, a presumably delayed life-threatening adverse reaction occurred. Thus, adverse pulmonary reaction to Thymoglobulin may not be evident intraoperatively or immediately postsurgery. Premonitory subtle signs such as tachypnea, along with a high index of suspicion, may allow practitioners to predict those patients who may progress to serious cardiopulmonary compromise.
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References
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Mayes JT, Dennis VW. Hoogwerf BJ. Pancreas transplantation in type 1 diabetes: hope vs reality. Cleve Clin J Med 2000; 67: 281–6.[Medline]
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Danovitch GM. Choice of immunosuppressive drugs and individualization of immunosuppressive therapy for kidney transplant patients. Transplant Proc 1999; 31: 2S–6S.
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Hong JC, Kahan BD. Immunosuppressive agents in organ transplantation: past, present, and future. Semin Nephrol 2000; 20: 108–25.[Web of Science][Medline]
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Philip AT, Gerson B. Toxicology and adverse effects of drugs used for immunosuppression in organ transplantation. Clin Lab Med 1998; 18: 755–65.[Medline]
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Gaber AO, et al. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation 1998; 66: 29–3.[Web of Science][Medline]
Accepted for publication June 29, 2001.
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Abstract
Introduction
