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Case Reports  |   June 2001
Continuous Veno-venous Hemofiltration for the Immediate Management of Massive Rhabdomyolysis after Fulminant Malignant Hyperthermia in a Bodybuilder
Author Affiliations & Notes
  • Michael R. Schenk, M.D.
    *
  • Dieter H. Beck, M.D., D.E.A.A., E.D.I.C., D.A., D.T.M. & H.
    *
  • Max Nolte, M.D.
  • Wolfgang J. Kox, M.D., Ph.D., F.R.C.P.
  • * Staff Anesthesiologist, † Resident, ‡ Professor of Anesthesiology and Critical Care Medicine and Chairman.
  • Received from the Department of Anesthesiology and Intensive Care Medicine, Charité University Hospital, Humboldt University Medical School, Berlin, Germany.
Article Information
Case Reports
Case Reports   |   June 2001
Continuous Veno-venous Hemofiltration for the Immediate Management of Massive Rhabdomyolysis after Fulminant Malignant Hyperthermia in a Bodybuilder
Anesthesiology 6 2001, Vol.94, 1139-1141. doi:
Anesthesiology 6 2001, Vol.94, 1139-1141. doi:
WE report a case of unsuspected fulminant malignant hyperthermia (MH) complicated by life-threatening hyperkalemia and massive rhabdomyolysis, which were managed successfully by early institution of continuous veno-venous hemofiltration (CVVH). In addition, we describe the kinetics of myoglobin elimination during prolonged hemofiltration.
Case Report
A 35-yr-old (100-kg) white man was admitted to the emergency room with history and clinical signs consistent with the diagnosis of peritonsilliar abscess. Axillary temperature was 36.5°C; leukocyte count was 15,900/μl. Medical history and physical examination results were unremarkable. The patient regularly performed bodybuilding training but did not report intake of any anabolic drugs or dietary supplements. He had no previous anesthetic exposure and no family history of adverse reactions to anesthesia.
Abscess drainage and tonsillectomy were performed during general anesthesia. Anesthesia was induced with propofol (3 mg/kg) and fentanyl (1.5 μg/kg). Rocuronium (0.4 mg/kg) was used for tracheal intubation. At the time of induction of anesthesia, all vital signs were within normal limits. Anesthesia was maintained with 60% nitrous oxide and isoflurane (1–2 vol %) in oxygen using a circle system with carbon dioxide absorber. The patient underwent mechanical ventilation. Ten minutes after induction, a sinus tachycardia of 140 beats/min developed; arterial blood pressure increased to 170/90 mmHg. Five minutes later, the capnograph readings increased from 35 to 70 mmHg, accompanied by an increase in body temperature from 36.9 to 38.9°C. Mechanical ventilation became increasingly impeded by the rigidity of the thoracic cage. Arterial oxygen saturation decreased to 80%. There was extreme muscle rigidity in the upper extremities, with hyperflexion in elbow and wrist joints, and hyperextension of the lower limbs. The diagnosis of MH was made. Anesthetic vapors were discontinued immediately, and ventilation with 100% oxygen was commenced.
Sodium bicarbonate (150 mmol) and 100 g glucose with 20 IU rapid-acting insulin and mannitol (1 g/kg) were administered, and within 25 min, 480 mg intravenous dantrolene had been administered. Arterial blood gases, obtained 20 min after induction, showed severe acidemia and hyperkalemia: pH, 6.94; arterial partial pressure of carbon dioxide (Pco2), 126 mmHg; base excess, −11.9 mm; standard bicarbonate, 15.4 mm; K+, 6.4 mm; Ca2+, 0.97 mm. Administration of sodium bicarbonate, glucose, and insulin was repeated. Despite fluid therapy with colloids (1,500 ml hydroxyethyl starch, 6%; 2,000 ml gelatine, 3.5%), the patient became hypotensive. Ventricular bradyarrhythmia with heart rate less than 35 beats/min developed, which responded to intravenous increments of 1 mg epinephrine and 4 g calcium gluconate. At that time, the serum potassium concentration was 8.6 mm. Central venous and double-lumen hemofiltration catheters were inserted, and continuous infusion of epinephrine (0.3 μg · kg−1· min−1) was commenced. Catheterization of the bladder revealed an intense discoloration of the urine, suggestive of massive myoglobinuria.
The patient was transferred to the intensive care unit 90 min after induction of anesthesia. He underwent mechanical ventilation; heart rate and blood pressure were 135 beats/min and 90/60 mmHg, respectively. Epinephrine was infused at a rate of 1.5 μg · kg−1· min−1. CVVH was started immediately. After 8 h, acid–base and electrolyte disturbances had improved (pH, 7.31; K+, 4.3 mm; Ca2+, 1.45 mm; Pco2, 32.8 mmHg; base excess, −9.1 mm; standard bicarbonate, 15.9 mm). He was hemodynamically stable, but acute oliguric renal failure developed. The patient was extubated 5 days after the event. He was discharged to the ward after 40 days without any neurologic sequelae but with markedly reduced muscle mass (weight loss, 20 kg) and generalized muscle weakness. Renal function was still impaired (serum creatinine concentration, 2.9 mg/dl), but no further renal replacement therapy was required.
Malignant hyperthermia susceptibility was confirmed by in vitro  contracture tests 4 months after the reaction. Testing was performed according to the protocol of the European Group of Malignant Hyperpyrexia 1 at the MH reference laboratory, Department of Anesthesiology, University of Leipzig, Leipzig, Germany. In vitro  contracture occurred at halothane and caffeine concentrations of 0.5 vol % and 0.5 mm, respectively.
Maximal plasma concentrations of myoglobin (278,000 μg/l) and creatinine kinase (106,800 IU/l) occurred within 24 h after surgery. CVVH was used for 28 consecutive days. After an initial increase, myoglobin plasma concentrations (CS) decreased by 25% per day during the first 5 days of CVVH and by almost 50% daily thereafter. Myoglobin concentrations reached a steady state after 14 days but remained increased (∼1,000 μg/l), despite continuation of hemofiltration for another 14 days. Changes in myoglobin concentrations were paralleled by almost identical changes in creatinine kinase plasma concentrations (fig. 1).
Fig. 1. Myoglobin (solid diamonds) and creatinine kinase (CK; open triangles) plasma concentrations during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH).
Fig. 1. Myoglobin (solid diamonds) and creatinine kinase (CK; open triangles) plasma concentrations during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH).
Fig. 1. Myoglobin (solid diamonds) and creatinine kinase (CK; open triangles) plasma concentrations during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH).
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We used a BM11/14 pump®(Baxter, Ettlingen, Germany) and a bicarbonate-based replacement solution containing 1.1 g/l glucose and 2.0 mm potassium (HF-Bic35/HF-EL210®; Fresenius, Bad Homburg, Germany). The hemofilter was a 1.1 m2polyamide S-membrane polyflux 11S®(Gambro, Hechingen, Germany). Blood flow and ultrafiltrate (UF) rates were 120 ml/min and 1.8 l/h, respectively. Replacement fluid was infused after dilution at a rate that matched the hourly ultrafiltration. Myoglobin concentrations in the ultrafiltrate (CUF), measured on the second day and 24 h later, were greater than 100,000 μg/l on both occasions. More accurate measurements would have necessitated further dilution and were not provided by the laboratory. The estimated minimal sieving coefficients (CUF/CS) for myoglobin were 0.36 and 0.37, respectively. The minimal amount of myoglobin removed by CVVH was 4.3 g/day (removed myoglobin = CUF× UF × 24 h).
Discussion
Increased muscle mass and potentially greater susceptibility of hypertrophic skeletal muscle cells may have contributed to the massive rhabdomyolysis in this patient. The use of anabolic drugs or dietary supplements is common among bodybuilders. Our patient strongly denied the intake of any of these substances but this possibility cannot be excluded definitely. The coexisting infection and the possible intake of such substances could have influenced muscle metabolism and could have further aggravated the severity of the MH reaction.
Peak myoglobin concentrations of 278,000 μg/l were far higher than those reported in other cases of severe nontraumatic rhabdomyolysis without renal impairment. In a 26-yr-old male, peak concentrations of 55,000 μg/l were reported. 2 In a 13-yr-old boy, maximal serum and urinary concentrations were 58,000 and 446,000 μg/l, respectively. Serum myoglobin concentrations decreased rapidly to 180 μg/l on day 5 after the MH reaction but remained increased for another week. By contrast, urinary concentrations returned to normal 2 days after the event. 3 This pattern suggests a two-phase elimination. Rapid renal excretion continues until a threshold is reached, followed by slow elimination, which also may involve extrarenal clearance mechanisms. 4 
In contrast to conventional hemodialysis, 5,6 hemofiltration is effective in removing larger-molecular-weight substances, such as myoglobin (17,000 Da). In an animal model (swine), 4 g equine myoglobin were administered intravenously. Within 6 h, 17 and 24% of the administered dose was removed by CVVH with ultrafiltrate rates of 1.8 and 2.9 l/h, respectively. Countercurrent dialysate flow (1 l/h) did not further improve myoglobin elimination. 7 
In the current patient, myoglobin was eliminated effectively by CVVH. Decreasing myoglobin release and extrarenal clearance mechanisms may have further contributed to the rapid decrease of myoglobin concentrations. 4 Initially, at least 4.3 g myoglobin were removed daily. The actual substance removal and the corresponding sieving coefficients were probably much higher because ultrafiltrate concentrations almost certainly exceeded 100,000 μg/l by far. Bellomo et al.  8 reported myoglobin removal of 1.8 g/day in three patients with rhabdomyolysis who underwent continuous hemodiafiltration. Amyot et al.  9 showed the efficacy of CVVH in a patient with myoglobin plasma concentrations of 92,000 μg/l; 700 mg myoglobin was removed in 33 h, using a 0.9-m2AN69 filter (UF, 2–3 l/h). The sieving coefficients for myoglobin were 0.4–0.6.
The semi-logarithmic plot of myoglobin plasma concentrations versus  time is characteristic of first-order elimination kinetics (fig. 2). A constant fraction of free myoglobin was removed daily until a steady state was reached after 14 days of hemofiltration. Thereafter, myoglobin concentrations remained almost unchanged although hemofiltration was continued, which confirms that moderately increased myoglobin plasma concentrations are not lowered effectively by hemodialysis or hemofiltration. 4,10 This may be attributed to the binding of myoglobin to plasma proteins and an ongoing liberation from damaged muscle cells.
Fig. 2. Semi-logarithmic plot of myoglobin plasma concentrations versus  time during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH). The solid line is the regression line; the dashed curves represent the 95% confidence interval of the regression. Regression coefficient r2= 0.90, P  < 0.001, analysis of variance.
Fig. 2. Semi-logarithmic plot of myoglobin plasma concentrations versus 
	time during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH). The solid line is the regression line; the dashed curves represent the 95% confidence interval of the regression. Regression coefficient r2= 0.90, P 
	< 0.001, analysis of variance.
Fig. 2. Semi-logarithmic plot of myoglobin plasma concentrations versus  time during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH). The solid line is the regression line; the dashed curves represent the 95% confidence interval of the regression. Regression coefficient r2= 0.90, P  < 0.001, analysis of variance.
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The pore size of hemofilter membranes usually allows the passage of particles up to a molecular weight of 20,000 Da. 10 Excessive release of myoglobin may exhaust the binding capacity of plasma proteins. The free, unbound myoglobin fraction is readily cleared by filtration until most of the circulating myoglobin is protein bound and no longer freely filtrable. In the current patient, this may have occurred at concentrations of approximately 1,000 μg/l. Similar clearance mechanisms may be present in severe rhabdomyolysis without renal failure, 2,3 although the threshold for myoglobin filtration may be different.
We consider hemofiltration a valuable therapeutic option in the initial management of severe cases of rhabdomyolysis. Besides the treatment of life-threatening hyperkalemia and acid–base disturbances, early institution of CVVH results in a rapid reduction of the circulating, free myoglobin. The potentially beneficial effects of early CVVH on outcome from acute myoglobinuric renal failure remain to be established.
References
European Malignant Hyperpyrexia Group: A protocol for the investigation of malignant hyperpyrexia susceptibility. Br J Anaesth 1984; 56: 1267–9European Malignant Hyperpyrexia Group:,
Fierobe L, Nivoche Y, Mantz J, Elalaoui Y, Veber B, Desmonts JM: Perioperative severe rhabdomyolisis revealing susceptibility to malignant hyperthermia. A nesthesiology 1998; 88: 263–5Fierobe, L Nivoche, Y Mantz, J Elalaoui, Y Veber, B Desmonts, JM
Laurence AS, Vanner GK, Collins W, Hopkins PM: Serum and urinary myoglobin following an aborted malignant hyperthermia reaction. Anaesthesia 1996; 51: 958–61Laurence, AS Vanner, GK Collins, W Hopkins, PM
Hällgren R, Karlsson FA, Roxin LE, Venge P: Myoglobin turnover-influence of renal and extrarenal factors. J Lab Clin Med 1978; 91: 246–54Hällgren, R Karlsson, FA Roxin, LE Venge, P
Winterberg B, Ramme K, Tenschert W, Winterberg G: Hemofiltration in moglobinuric acute renal failure. Int J Artif Organs 1990; 13: 113–6Winterberg, B Ramme, K Tenschert, W Winterberg, G
Nicolau DP, Feng YJ, Wu AH, Bernstein SP, Nightingale CH: Evaluation of myoglobin clearance during continuous hemofiltration in a swine model of acute renal failure. Int J Artif Organs 1996; 19: 578–81Nicolau, DP Feng, YJ Wu, AH Bernstein, SP Nightingale, CH
Nicolau D, Feng YS, Wu AH, Bernstein SP, Nightingale CH: Myoglobin clearance during continuous veno-venous hemofiltration with or without dialysis. Int J Artif Organs 1998; 21: 205–9Nicolau, D Feng, YS Wu, AH Bernstein, SP Nightingale, CH
Bellomo R, Daskalakis R, Parkin G, Boyce N: Myoglobin clearance during acute continuous hemodiafiltration. Intensive Care Med 1991; 17: 509Bellomo, R Daskalakis, R Parkin, G Boyce, N
Amyot SL, Leblanc M, Thibeault Y, Geadah D, Cardinal J: Myoglobin clearance and removal during continuous venovenous hemofiltration. Intensive Care Med 1999; 25: 1169–72Amyot, SL Leblanc, M Thibeault, Y Geadah, D Cardinal, J
Hart PM, Feinfeld DA, Briscoe AM, Nurse HM: The effect of renal failure and hemodialysis on serum and urine myoglobin. Clinical Nephrology 1982; 18: 141–3Hart, PM Feinfeld, DA Briscoe, AM Nurse, HM
Fig. 1. Myoglobin (solid diamonds) and creatinine kinase (CK; open triangles) plasma concentrations during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH).
Fig. 1. Myoglobin (solid diamonds) and creatinine kinase (CK; open triangles) plasma concentrations during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH).
Fig. 1. Myoglobin (solid diamonds) and creatinine kinase (CK; open triangles) plasma concentrations during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH).
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Fig. 2. Semi-logarithmic plot of myoglobin plasma concentrations versus  time during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH). The solid line is the regression line; the dashed curves represent the 95% confidence interval of the regression. Regression coefficient r2= 0.90, P  < 0.001, analysis of variance.
Fig. 2. Semi-logarithmic plot of myoglobin plasma concentrations versus 
	time during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH). The solid line is the regression line; the dashed curves represent the 95% confidence interval of the regression. Regression coefficient r2= 0.90, P 
	< 0.001, analysis of variance.
Fig. 2. Semi-logarithmic plot of myoglobin plasma concentrations versus  time during the first 14 consecutive days of continuous veno-venous hemofiltration (CVVH). The solid line is the regression line; the dashed curves represent the 95% confidence interval of the regression. Regression coefficient r2= 0.90, P  < 0.001, analysis of variance.
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