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J Thorac Cardiovasc Surg 1998;116:654-655
© 1998 Mosby, Inc.
BRIEF COMMUNICATIONS |
Victoria, Australia
From the Department of Cardiothoracic Surgery, Monash Medical Centre, Victoria, Australia.
Received for publication April 13, 1998. Accepted for publication May 18, 1998. Address for reprints: Mr J. M. Alvarez, Consultant Cardiothoracic Surgeon, Monash Medical Centre, 246 Clayton Rd, Clayton 3168, Victoria, Australia.
Generalized myalgia and rhabdomyolysis in association with the hydroxy methylglutaryl coenzyme A reductase inhibitors (statins) has not been previously described after cardiac operations. We report a case of severe myalgia and rhabdomyolysis producing renal failure necessitating hemodialysis and prolonged mechanical ventilation.
Clinical summary
A 62-year-old man with unstable angina refractory to intravenous medical therapy was referred for urgent redo coronary artery bypass graft (CABG) surgery. Cardiac catheterization revealed a patent left internal thoracic artery (ITA) graft to the left anterior descending coronary artery (LAD) and diseased saphenous vein grafts (SVGs) to the first circumflex marginal (CX1) and posterior descending coronary artery. The native circulation had 90% stenoses affecting the LAD, CX, and posterior descending vessels. Left ventricular function was normal. Coronary risk factors were current cigarette smoking and hyperlipidemia. Medications included aspirin (Cardiprin, Reckitt & Coleman) 150 mg daily, simvastatin (Lescol, Sandoz) 10 mg daily, and atenolol (Noten, Alphafarm) 50 mg.
Anesthesia was achieved with fentanyl tartrate (Fentanyl, Astra) 1 mg, pancuronium bromide (Pavulon, Organon Teknika) 8 mg, and intravenous propafol (Diprovan, ICI). Cardiopulmonary bypass with moderate systemic hypothermia to 32°C was established. Antegrade and retrograde blood cardioplegia was used for myocardial protection. A free right ITA was grafted onto the posterior descending artery, and the left radial artery was used to sequentially graft the CX1 and CX2.
Discontinuation from cardiopulmonary bypass required no inotropic support. The immediate postoperative course was associated with a high cardiac output/low systemic vascular resistance state (cardiac output, 9 L/min; systemic vascular resistance, 400 dynes · s ·cm5 requiring intravenous norepinephrine (Levophed, Abbott) 2 µg/kg per minute. The postoperative chest x-ray film revealed right-sided mid-zone pneumonia that was treated with intravenous ceftriaxone (Rocephin, Hoffmann-LaRoche) 2 g daily. Gas exchange however was satisfactory.
Forty-eight hours after the operation, unheralded oliguria (30 mL/h) despite a satisfactory cardiac output (6l L/min), associated with an increase in creatinine (346 mmol/L) and hyperkalemia (potassium, 6.9 mmol/L) developed. The oliguria was unresponsive to intravenous furosemide 80 mg/h (Lasix, DBL), intravenous dopamine HCl (Dopamine, CSL) at 3 µg/kg per hour, and intravenous mannitol 20% (Osmitrol, Baxter) at 10 mL/h. The patient's creatine kinase (CK) level increased to 9000 U/L with an MB isoenzyme of 39 U/L. Hemodialysis was commenced because of continuing hyperkalemia and hypercreatininemia (creatine level 558 mmol/L).
Generalized myalgia also developed. Despite satisfactory gas exchange, the patient could not generate an adequate tidal volume (100 mL) and required mechanical ventilation. The CK level peaked on day 4 at 14,746 units/L, returning to normal by postoperative day 8. The patient required hemodialysis for 4 days and mechanical ventilation for 25 days. He was discharged home 15 days later. Streptococcus viridans and coagulase-negative Staphylococcus were the sole micro-organisms cultured; assays for Legionella pneumophila were negative.
Discussion
The statins lower low-density lipoprotein levels and serum total cholesterol and raise high-density lipoprotein levels by 40%, 30%, and 10% respectively.
1 Statin therapy has proven beneficial in patients after CABG. Aggressive reduction of serum low-density lipoprotein levels (<2.5 mmol/L) after CABG will reduce disease progression in SVGs, the development of new plaques, and the risk of total occlusions by 31%, 52%, and 37.5%, respectively. 2 Currently, 25% of our patients referred for CABG are receiving statins.
The statins are well tolerated with a low incidence of side effects. Myopathy occurs in 0.1% to 0.5% of patients. 3 Concomitant use of lovastatin with gemfibrozil, niacin, and cyclosporine A (INN: ciclosporin) increases the relative risk of myopathy to 5%, 2%, and 28%, respectively. 3,4 Impaired hepatic function can potentially heighten the risk of side effects by increasing their bio-availability. 3,4 Although the incidence of rhabdomyolysis is rare (0.04%-0.2%), acute renal failure resulting from rhabdomyolysis and intraoperative rhabdomyolysis has been documented. 4,5 Patients have been receiving statin therapy for 2 to 16 months when this complication has occurred, without any apparent trigger. 4,5 This patient had been receiving simvastatin for 7 years with no adverse effect.
In this case, preoperative and immediate postoperative renal and hepatic function were within normal limits. The intitial CK elevation was consistent with harvesting the right ITA. Significant CK elevation occurred 24 hours after the operation, peaking at 72 hours. The serum CK rise mirrored the elevation in serum creatinine, the development of refractory oliguria, and the development of generalized myalgia and respiratory muscle weakness.
No known drug(s) associated with rhabdomyolysis, itself rare, 4 were administered, nor were any metabolic factors present that are capable of potentiating this event. When rhabdomyolysis has been reported in patients undergoing long-term therapy, no acute causative factor is apparent. 3,4 Rosenberg and colleagues, 5 however, have documented intraoperative rhabdomyolysis associated with pravastatin in cases in which the operation was thought to be the trigger. Although speculative, 7 years of uneventful simvastatin therapy in this case, together with the report by Rosenberg's group, indicates to us that the timing of this complication and operation were not coincidental.
References
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