Ann Thorac Surg 2002;74:1251-1252
© 2002 The Society of Thoracic Surgeons
Case report
Type B lactic acidosis: a rare complication of antiretroviral therapy after cardiac surgery
Bernard G. Vasseur, MD*a,
Hideki Kawanishi, MDb,
Nahir Shah, MDc,
Mark L. Anderson, MDa
a Department of Surgery and Medicine, University of Medicine, New Brunswick, New Jersey, USA
b Dentistry of New Jersey—Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
c Department of Cardiology, Saint Peters University Hospital, New Brunswick, New Jersey, USA
Accepted for publication June 10, 2002.
* Address reprint requests to Dr Vasseur, Division of Thoracic Surgery, University of Medicine and Dentistry of New Jersey—Robert Wood Johnson Medical School, PO Box 19, New Brunswick, NJ 08903-0019 USA
e-mail: vasseubg{at}umdnj.edu
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Abstract
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This report describes a 47-year-old woman with human immunodeficiency virus (HIV) and end-stage renal disease on hemodialysis, treated with combination antiretroviral drug therapy, who developed an acute, severe type B lactic acidosis 24 hours after homograft root replacement for endocarditis. She fully recovered after HIV medication was discontinued, along with administration of riboflavin and supportive measures including hemodialysis. The timing of this complication and previous reports suggest that open heart surgery may be a risk factor for nonischemic (type B) lactic acidosis in patients taking nucleoside analogue reverse transcriptase inhibitors.
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Introduction
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Lactic acidosis in the absence of tissue ischemia is the hallmark of type B lactic acidosis [1]. It is rarely seen after open heart surgery [2] where lactic acidosis frequently is due to ischemia, ie, type A lactic acidosis [3]. Type B lactic acidosis is well-described in patients on antiretroviral therapy [4] and is associated with a high mortality [5]. Both short- and long-term use of nucleoside analog reverse transcriptase inhibitors (NARTI) have been implicated. Inhibition of enzymes needed for mitochondrial DNA synthesis results in impaired mitochondrial oxydative phosphorylation and lactic acidosis [6–8]. We report the case of a woman who developed sudden severe type B lactic acidosis immediately following homograft root replacement.
A 47-year-old woman, with diagnosis of human immunodeficiency virus (HIV) since 1993, was admitted with fevers. Three months prior to admission, she developed end-stage renal disease due to HIV-associated nephropathy and chronic hemodialysis was initiated. On admission, echocardiogram demonstrated aortic valve endocarditis with 1-cm vegetation. Blood cultures were positive for Staphylococcus aureus.
The permanent dialysis catheter was presumably the source of endocarditis and was removed. With intravenous vancomycin therapy, guided with every-other-day serum level, the blood culture became negative. Weekly echocardiograms showed a progressive enlargement of the aortic valve vegetation with worsening moderate aortic insufficiency. The patient was scheduled to undergo aortic valve replacement. While awaiting surgery, she developed an acute left foot ischemia. A leg angiogram showed an acute embolus to the popliteal artery trifurcation. A 0.9 x 0.5 x 0.4-cm thrombus was removed during thrombectomy with return of pedal pulses and normalization of clinical symptoms. No control angiogram was done and the patient was transferred to the floor. The cultures from the embolus were positive for Staphylococcus aureus. Without coronary angiogram, she was brought to the operating room 48 hours later for aortic root replacement with a 24-mm homograft (Cryolife, Inc, Kennesaw, GA) under balanced general anesthesia. The procedure was performed at 32°C keeping a systemic perfusion pressure around 70 mm Hg. The aortic cross-clamp time and bypass time were 115 and 160 minutes, respectively. Operative findings confirmed the presence of a 2-cm vegetation mobile within the aortic orifice. There was no destruction of the aortic annulus. A large tear of the noncoronary cusp was found. Microscopic examination showed numerous colonies of Staphylococcus aureus within the vegetation. The initial postoperative course was uncomplicated with a heart rate of 80 c/min, central venous pressure of 12 mm Hg, a cardiac index of 2.7 l/min/m2, pulmonary artery pressure 25/13 mm Hg, and systemic vascular resistance of 970 dynes·sec·m2/cm5. The next day, a low-dose epinephrine drip was discontinued, the patient extubated, and her oral antiretroviral medication regimen of lamivudine (Epivir, Glaxo Wellcome Inc, Research Triangle Park, NC), stavudin (Zerit, Bristol-Meyers Squibb Company, Princeton, NJ), and the protease inhibitors indinavir (Crixivan, Merck and Company Inc, West Point, PA) and ritonavir (Norvir, Abbott Laboratories Inc, North Chicago, IL) were restarted.
That evening, while sitting in a chair, she developed labored breathing without additional symptoms or significant changes in her hemodynamic parameters. Her arterial blood gas and chemistry revealed a high anion gap metabolic acidosis with pH of 7.10 and bicarbonate 13 mmoles/l. Her leukocyte count was elevated at 44,000/ml from 28,000/ml before the procedure. She was reintubated and acidemia corrected with bicarbonate infusion. Her cardiac function was normal by transthoracic echocardiography and pulmonary artery catheter measurements. Subsequently, she was found to have an elevated lactic acid level of 26.5 Meq/L.
She underwent an exploratory laparotomy. No sources of ischemia or sepsis were found. The retroviral medications were stopped. A multivitamin preparation including thiamine was given, and riboflavin was started at 25 mg daily by orogastric tube. The postoperative course was remarkable for difficulty in controlling her serum glucose with large variation of glycemia up to 700 mmoles/dl. Continuous veno-veno hemodialysis was started but discontinued due to its contribution to persistent hyperglycemia; this was subsequently resolved with an insulin drip up to 130 units per hour. Lactic acid level began to improve around postoperative day 5. Liver function initially worsened with an ALT (serum alanine aminotransferase) of 272 U/L, AST (serum aspartate aminotransferase) of 1,025 U/L, and total bilirubin as high as 5.1 mg/dl.
On postoperative day 9, the lactic acidosis continued to improve with a level of 2.7 Meq/L. On postoperative day 10, she was extubated. She progressively improved and was discharged to home 1 month later, off antiretroviral therapy.
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Comment
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The goal of antiretroviral therapy for treatment of HIV infection is reduction of viral replication by using medications targeting reverse transcriptase, the key enzyme in HIV replication. Anti-HIV medications are classified into three classes: NARTI, nonnucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitors. Highly active antiretroviral therapy involves the combination of these classes of medications, typically a protease inhibitor plus two NARTI or one NNRTI as initial therapy.
Of these classes of anti-HIV medications, it is the NARTI that have been implicated in type B lactic acidosis [1]. In our patient, the mechanism of hyperlactatemia was mainly due to alteration of lactate utilization.
Inhibition of human mitochondrial DNA polymerase gamma by nonnucleoside reverse transcriptase inhibitors may result in creation of DNA mutations (deletions) [7]. This results in defective mitochondrial enzymes responsible for oxidative phosphorylation. Thus, the mitochondrial respiratory chain is disrupted and conversion to anaerobic metabolism with enhanced lactate production occurs. Hepatic steatosis has been documented in patients taking NNRTIs. This hepatic dysfunction exacerbates an impaired lactic acid clearance and contributes to hyperlacticacidemia [9]. Reported possible treatment for type B lactic acidosis secondary to antiretroviral medication has included hemodialysis [10], riboflavin [11–12], thiamine [11], L-carnitine, coenzyme Q, and vitamin C in addition to withdrawal of NARTIs. Our patient was treated with discontinuation of NARTI, riboflavin, and supportive care (including hemodialysis).
We conclude that when presented with the diagnosis of high anion gap metabolic acidosis after cardiac surgery, one should consider type B lactic acidosis in patients taking NARTI. Discontinuation of antiretroviral therapy and initiation of thiamine, riboflavin, or other antioxidants should be considered. Full supportive therapy including mechanical ventilation, control of glycemia, and hemodialysis should be instituted as needed.
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Acknowledgments
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The authors thank Dr Christophe Acar for his technical advice and Dr Richard Sherman for his thorough review of the manuscript.
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References
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Abstract
Introduction
