Extremely High Creatine Kinase Activity in Rhabdomyolysis without Acute Kidney Injury.

BACKGROUND Elevation of creatine kinase (CK) activity has been shown to be predictive of acute kidney injury (AKI) in rhabdomyolysis. Patients with extremely high CK activity with preserved renal function are uncommon. This report describes a case of non-traumatic rhabdomyolysis, with a markedly elevated CK activity, without associated AKI. CASE REPORT A 22-year-old male presented with severe generalized myalgias and darkened urine for 1 week prior to his admission. The patient presented to the Emergency Department with initial CK activity of >40 000 U/L and a serum creatinine level of 0.77 mg/dL. Urinalysis was positive for myoglobinuria. Serum cystatin C confirmed an estimated glomerular filtration rate of 144 mL/min/1.73 m². Several causes of rhabdomyolysis, including viral infections, Lyme disease, viral hepatitis, hypothyroidism, and cocaine abuse were investigated; however, all were negative. He was given a bolus of 2 liters of normal saline and continued on intravenous normal saline at 250 mL/hour throughout his hospital stay. Urine output remained adequate. We were able to quantify his serum CK activity by dilution method, which revealed a serum CK activity of >150 000 U/L. His CK levels consistently trended down with treatment. CONCLUSIONS An extremely high CK activity in rhabdomyolysis may lead to AKI. However, preserved kidney function is possible. Young age, no concurrent cocaine use, and adequate oral fluid hydration may prevent AKI in rhabdomyolysis. Physicians need to remain vigilant for cases of rhabdomyolysis that have not yet caused renal compromise.

Mitochondria-Associated Matrix Metalloproteinases 2 and 9 in Acute Renal Pathologies.

Activities of MMP-2 and MMP-9 in the cytoplasm and mitochondria of kidney cells were evaluated on the models of acute renal pathologies: pyelonephritis, rhabdomyolysis, and ischemia/reperfusion of the kidney. In acute pyelonephritis, a significant increase in the level of MMP-2 and MMP-9 in kidney cells and the appearance of mitochondrial MMP-2 isoform with a lower molecular weight, but still exhibiting proteolytic activity were observed. A direct correlation between the level of MMP-2 and MMP-9 in the kidney and the severity of inflammation in pyelonephritis was revealed. Obviously, the appearance of active protease in the mitochondria of the kidney cells could have an impact on their functioning and, generally, on the fate of renal cells in this pathology.

Volatile anesthesia for a child with LPIN1 gene mutation and recurrent rhabdomyolysis.

We report the case of a boy with LPIN1 gene mutation presenting for adenotonsillectomy who was successfully managed with preoperative saline and glucose infusion followed by balanced anesthesia including sevoflurane. The anesthetic planning is described as there is no modern literature to guide the perioperative management of these children.

Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury.

Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine and blood urea nitrogen levels as well as attenuated renal tubular damage in injured kidneys. HDAC6 inhibition also resulted in decreased expression of NGAL, reduced apoptotic cell, and inactivated caspase-3 in the kidney after acute injury. Moreover, injury to the kidney increased phosphorylation of nuclear factor (NF)-κB and expression of multiple cytokines/chemokines including tumor necrotic factor-α and interleukin-6 and monocyte chemoattractant protein-1, as well as macrophage infiltration. Treatment with TA attenuated all those responses. Finally, HDAC6 inhibition reduced the level of oxidative stress by suppressing malondialdehyde (MDA) and preserving expression of superoxide dismutase (SOD) in the injured kidney. Collectively, these data indicate that HDAC6 contributes to the pathogenesis of rhabdomyolysis-induced AKI and suggest that HDAC6 inhibitors have therapeutic potential for AKI treatment.

Deregulation of mitochondrial functions provoked by long-chain fatty acid accumulating in long-chain 3-hydroxyacyl-CoA dehydrogenase and mitochondrial permeability transition deficiencies in rat heart--mitochondrial permeability transition pore opening as a potential contributing pathomechanism of cardiac alterations in these disorders.

Mitochondrial trifunctional protein and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiencies are fatty acid oxidation disorders biochemically characterized by tissue accumulation of long-chain fatty acids and derivatives, including the monocarboxylic long-chain 3-hydroxy fatty acids (LCHFAs) 3-hydroxytetradecanoic acid (3HTA) and 3-hydroxypalmitic acid (3HPA). Patients commonly present severe cardiomyopathy for which the pathogenesis is still poorly established. We investigated the effects of 3HTA and 3HPA, the major metabolites accumulating in these disorders, on important parameters of mitochondrial homeostasis in Ca(2+) -loaded heart mitochondria. 3HTA and 3HPA significantly decreased mitochondrial membrane potential, the matrix NAD(P)H pool and Ca(2+) retention capacity, and also induced mitochondrial swelling. These fatty acids also provoked a marked decrease of ATP production reflecting severe energy dysfunction. Furthermore, 3HTA-induced mitochondrial alterations were completely prevented by the classical mitochondrial permeability transition (mPT) inhibitors cyclosporin A and ADP, as well as by ruthenium red, a Ca(2+) uptake blocker, indicating that LCHFAs induced Ca(2+)-dependent mPT pore opening. Milder effects only achieved at higher doses of LCHFAs were observed in brain mitochondria, implying a higher vulnerability of heart to these fatty acids. By contrast, 3HTA and docosanoic acids did not change mitochondrial homeostasis, indicating selective effects for monocarboxylic LCHFAs. The present data indicate that the major LCHFAs accumulating in mitochondrial trifunctional protein and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiencies induce mPT pore opening, compromising Ca(2+) homeostasis and oxidative phosphorylation more intensely in the heart. It is proposed that these pathomechanisms may contribute at least in part to the severe cardiac alterations characteristic of patients affected by these diseases.

Protective effect of focal adhesion kinase against skeletal muscle reperfusion injury after acute limb ischemia.

OBJECTIVES: In cardiac muscle, ischemia reperfusion (IR) injury is attenuated by mitochondrial function, which may be upregulated by focal adhesion kinase (FAK). The aim of this study was to determine whether increased FAK levels reduced rhabdomyolysis in skeletal muscle too. MATERIAL AND METHODS: In a translational in vivo experiment, rat lower limbs were subjected to 4 hours of ischemia followed by 24 or 72 hours of reperfusion. FAK expression was stimulated 7 days before (via somatic transfection with pCMV-driven FAK expression plasmid) and outcomes were measured against non-transfected and empty transfected controls. Slow oxidative (i.e., mitochondria-rich) and fast glycolytic (i.e., mitochondria-poor) type muscles were analyzed separately regarding rhabdomyolysis, apoptosis, and inflammation. Severity of IR injury was assessed using paired non-ischemic controls. RESULTS: After 24 hours of reperfusion, marked rhabdomyolysis was found in non-transfected and empty plasmid-transfected fast-type glycolytic muscle, tibialis anterior. Prior transfection enhanced FAK concentration significantly (p = 0.01). Concomitantly, levels of BAX, promoting mitochondrial transition pores, were reduced sixfold (p = 0.02) together with a blunted inflammation (p = 0.01) and reduced rhabdomyolysis (p = 0.003). Slow oxidative muscle, m. soleus, reacted differently: although apoptosis was detectable after IR, rhabdomyolysis did not appear before 72 hours of reperfusion; and FAK levels were not enhanced in ischemic muscle despite transfection (p = 0.66). CONCLUSIONS: IR-induced skeletal muscle rhabdomyolysis is a fiber type-specific phenomenon that appears to be modulated by mitochondria reserves. Stimulation of FAK may exploit these reserves constituting a potential therapeutic approach to reduce tissue loss following acute limb IR in fast-type muscle.

Critical illness in energy metabolism genetic disorder: rhabdomyolysis, acute kidney injury, respiratory arrest / Enfermedad crítica por trastorno genético en el metabolismo de la energía: rabdomiolisis, lesión renal aguda, paro respiratorio

In very long-chain acylCoA dehydrogenase deficiency (VLCAD), the activity of this enzyme is either reduced or absent with the inability to use long-chain fatty acids as energy substrates. A 25-year old male with VLCAD was admitted to the Emergency Department of Policlinico Teaching Hospital (Modena, Italy) for generalized weakness and oliguria, after a period of physical and mental stress and inadequate compliance to a long-chain fatty acid free diet. Laboratory tests were compatible with acute kidney injury. Seventy-two hours after admission, the subject had an episode of chest pain with elevated markers of myocardial necrosis. The rapid deterioration of muscular strength and the subsequent worsening respiratory failure necessitated ventilator support within the local Medical Intensive Care Unit. There, the patient showed a prompt normalization of respiratory parameters and a steady improvement of renal function. An inadequate compliance to lifestyle and dietary restriction in VLCAD may trigger severe and potentially lethal crisis. The in-hospital management of these patients calls for early intensive care admission as their conditions may deteriorate without warning.

En el caso de deficiencia de acylCoA deshidrogenasa de cadena muy larga (VLCAD), o bien se reduce la actividad de esta enzima, o la misma se halla ausente con la consiguiente incapacidad para utilizar los ácidos grasos de cadena larga como sustratos de energía. Un hombre de 25 años fue ingresado con VLCAD fue admitido en el Departamento de emergencia del Hospital Policlínico Docente Hospital de Modena, en Italia, a causa de presentar debilidad generalizada y oliguria, después de un período de estrés físico y mental, y por no cumplir adecuadamente con una dieta libre de ácidos grasos de cadena larga. Las pruebas de laboratorio eran compatibles con una lesión renal aguda. Setenta y dos horas después de su ingreso, el sujeto tuvo un episodio de dolor en el pecho con marcadores elevados de necrosis miocárdica. El rápido deterioro de la fuerza muscular, y el posterior empeoramiento de la insuficiencia respiratoria requirieron el apoyo de un ventilador en la Unidad de Cuidados Médicos Intensivos. Una vez allí, el paciente mostró una pronta normalización de los parámetros respiratorios, y una constante mejoría de la función renal. Un inadecuado cumplimiento con las restricciones dietéticas y el estilo de vida en los casos de VLCAD, pueden desatar una crisis grave y potencialmente fatal. El tratamiento intrahospitalario de estos pacientes requiere un ingreso temprano en cuidados intensivos, ya que sus condiciones pueden deteriorarse sin previo aviso.

Relationship of creatine kinase elevation and acute kidney injury in pediatric trauma patients.

BACKGROUND: Rhabdomyolysis following trauma has been associated with renal impairment. Nevertheless, the literature is scant in risk assessment of acute kidney injury (AKI) and survival in children experiencing posttraumatic rhabdomyolysis. METHODS: After institutional review board approval was obtained, the registry of an urban trauma center was reviewed for pediatric (age < 18 years) trauma admissions with available creatine kinase (CK) values. Variables extracted included demographics and trauma severity indices along with serum creatine, CK, and Blood Urea Nitrogen (BUN) values. AKI was defined per pediatric RIFLE (Risk, Injury, Failure, Loss, End stage) definition. Regression models were deployed to determine the independent risk factors for AKI and CK levels. RESULTS: Overall, 521 patients constituted the study sample. AKI occurred in 70 patients (13.4%), with correlation to CK values in excess of 3,000 IU/L (41.4% vs. 4.9%, adjusted p < 0.001). Independent risk factors for AKI proved to be CK level of 3,000 or greater (adjusted odds ratio [AOR], 11.02; 95% confidence interval [CI], 4.56-26.64; p < 0.001), Injury Severity Score (ISS) of 15 or less (AOR, 0.25; 95% CI, 0.10-0.61), Glasgow Coma Scale (GCS) score of 8 or less (AOR, 15.00; 95% CI, 4.98-44.94), abdominal Abbreviated Injury Scale (AIS) score of 3 or less (AOR, 3.14; 95% CI, 1.04-5.36), imaging studies with contrast of 3 or less (AOR, 3.81; 95% CI, 1.37-10.57), blunt mechanism of injury (AOR, 2.76; 95% CI, 1.17-6.49), administration of nephrotoxic agents (AOR, 4.81; 95% CI, 1.23-18.79), and requirement for fluids administration in the emergency department (AOR, 2.36; 95% CI, 1.04-5.36). Mortality in the study sample with CK values of 3,000 or greater versus less than 3,000 IU/L did not reach statistical significance (25.0% vs. 9.3%, adjusted p = 0.787). CONCLUSION: AKI in pediatric posttraumatic rhabdomyolysis occurs in 13% of trauma patients. CK values of 3,000 IU/L or greater pose a significant adjusted risk for AKI. Aggressive monitoring of CK values in pediatric trauma patients is warranted. LEVEL OF EVIDENCE: Prognostic study, level III.

Positioning injury, rhabdomyolysis, and serum creatine kinase-concentration course in patients undergoing robot-assisted radical prostatectomy and extended pelvic lymph node dissection.

BACKGROUND AND PURPOSE: During robot-assisted radical prostatectomy (RARP), patients remain in a steep Trendelenburg position. This can cause positioning injuries as well as rhabdomyolysis. The primary diagnostic indicator of rhabdomyolysis is elevated serum creatine kinase (CK). We investigate whether RARP with extended pelvic lymph node dissection (ePLND) in a prolonged extreme Trendelenburg position can cause positioning injuries and rhabdomyolysis. PATIENTS AND METHODS: We performed a prospective study of the first 60 patients undergoing RARP and ePLND for organ-confined prostate cancer at our institute. Positioning injuries were graded according to three degrees of clinical severity. Serum-CK, serum-pH, and base excess (BE) were measured before, during, and for 5 days after surgery. Rhabdomyolysis was defined by serum-CK levels >5000 IU/L. RESULTS: Median operative time was 317 minutes (range 200-475 min); median time in the Trendelenburg position was 282 minutes (range 170-470 min). Serum-CK was significantly elevated 6 hours postoperatively, peaking at 18 hours postoperatively. Serum-CK levels did not correlate with pH, BE, and perioperative creatinine values. Serum-CK course shows weak correlation with body mass index (BMI), operative time, Trendelenburg position time, and medium correlation with positioning injuries of any degree. Twenty-one of the 60 (35%) patients showed positioning-related injuries: 16 (27%) patients degree I, 2 (3%) patients degree II, and 3 (5%) patients degree III. Rhabdomyolysis developed in 10 patients. Postoperative renal failure did not develop in any patient receiving postoperative hypervolemic diuretic therapy nor any patient with injuries degrees I, II, or III. conclusion: Clinically relevant positioning injuries and rhabdomyolysis can occur in patients who are subjected to prolonged extreme Trendelenburg position during RARP and ePLND, especially at the beginning of the learning curve. Serum-CK increases significantly after surgery, peaking 18 hours postoperatively. Serum-CK elevation alone is not predictive of positioning injury. By very long operative and Trendelenburg times as well as high BMI with visible position injuries, we recommend serum-CK measurement 6 and 18 hours postoperatively followed by hypervolemic therapy to prevent possible renal injury from rhabdomyolysis if serum-CK >5000 IU/L.

Investigation of the relationship between serum creatine kinase and genetic polymorphisms in military recruits.

Genetic polymorphisms may explain why certain individuals will develop exertional rhabdomyolysis (ER) or markedly elevated serum creatine kinase (CK) levels following exertion, while others in the same environment, performing the same exertion, do not. Prospectively, 499 recruits were evaluated during the initial fortnight of Army basic training. Serum CK levels were determined before and during that time. Eleven candidate genetic polymorphisms were studied and compared to CK levels. No subjects developed ER. Baseline CK was significantly greater in interleukin-6 G174C GG and myosin light chain kinase 2 (MLCK 2) AA subjects. Intertraining levels were significantly greater in angiotensin I-converting enzyme D/D and interleukin-6 GG subjects. Among African-Americans, those with MLCK2 AA had greater baseline CK (1,352 +/- 1,102.8 IU/L) than AC and CC genotypes (536.9 +/- 500.6). African-American men have the highest baseline levels and are more likely to have MLCK AA genotype. Whether this finding is associated with an increased incidence of ER requires further study.

Trabectedin-related rhabdomyolysis: an uncommon but fatal toxicity.

Rhabdomyolysis is defined as the dissolution of striped muscle characterized by the leakage of intracellular muscle components into the circulation, which can ultimately lead to renal failure with a possible fatal outcome. Trabectedin is a potential cause of rhabdomyolysis. Herein, we describe a case of rhabdomyolysis in a female patient with recurrent metastatic leiomyosarcoma of the uterus and who had full recovery, and we review the already published cases in order to identify a common pattern of emergence.

Cerivastatin in vitro metabolism by CYP2C8 variants found in patients experiencing rhabdomyolysis.

OBJECTIVES: Cerivastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor withdrawn from the market because of serious adverse effects, is metabolized primarily by CYP2C8. The occurrence of associated myotoxicity and rhabdomyolysis were attributed to altered cerivastatin pharmacokinetics on account of gemfibrozil-inhibition or genetic variations in CYP2C8 and drug transporters involved in cerivastatin clearance. However, the effect of CYP2C8 genetic variation on cerivastatin metabolism has not been fully elucidated. METHODS: In this study, patients (n=126) with confirmed cases of rhabdomyolysis after cerivastatin administration had their CYP2C8 gene resequenced and the metabolism of cerivastatin by the discovered CYP2C8 variants was assessed in proteins expressed in Escherichia coli. RESULTS: In this unique patient population, 12 novel single nucleotide polymorphisms were discovered of which six were exclusively found in patients not using gemfibrozil. Three rare exonic variants resulted in amino acid substitutions and a frame shift deletion (V472fsL494 generating a defective mostly heme-free CYP2C8 protein). A particular promoter located deletion (-635_-634delTA) was tightly linked to CYP2C8*3. Heterologously expressed CYP2C8.3 and CYP2C8.4 displayed an increase in cerivastatin metabolic clearance of up to six-fold compared with the wild-type enzyme. Similarly, an independent sample of microsomes from human livers carrying the CYP2C8*3 and CYP2C8*4 alleles exhibited a 2-fold to 14-fold increase in normalized cerivastatin intrinsic clearance, compared with microsomes from livers carrying only the wild type allele. CONCLUSION: Gain or loss of catalytic function found in the CYP2C8 gene could certainly alter cerivastatin pharmacokinetics and may influence, at least in part, susceptibility to the development of myotoxicity.

Intraoperative fluid replacement and postoperative creatine phosphokinase levels in laparoscopic bariatric patients.

BACKGROUND: Morbid obesity and bariatric surgery are both risk factors for the development of postoperative rhabdomyolysis (RML). RML results from injury to skeletal muscle, and a serum creatine phosphokinase (CK) level >1,000 IU/L is considered diagnostic of RML. The aim of this study was to determine if intraoperative intravenous fluid (IVF) volume affects postoperative CK levels following laparoscopic bariatric operations. STUDY DESIGN: Prospective, single blinded, and randomized trial was conducted. METHODS: Patients scheduled to undergo laparoscopic sleeve gastrectomy, adjustable gastric band, or Roux-en-Y gastric bypass operations were randomized into two groups. Subjects in Group A received 15 ml/kg total body weight (TBW) of IV crystalloid solution during surgery, while subjects in Group B received 40 ml/kg TBW. Preoperative and postoperative CK and creatinine levels and intra- and postoperative urine output were monitored and recorded. RESULTS: Forty-seven patients were assigned to Group A and 53 patients to Group B. Group B patients had significantly higher urine output in the operating room, in the post-anesthesia care unit (PACU), and on postoperative days 0 and 1. Group B patients also had significantly lower serum creatinine level in the PACU and a trend towards lower creatinine levels on postoperative days 0, 1, and 2. There were no statistical differences in CK levels at any time between the two groups. Four patients in Group A and three patients in Group B developed postoperative RML. CONCLUSIONS: Conservative (15 ml/kg) versus liberal (40 ml/kg) intraoperative IVF administration did not change the incidence of RML in patients undergoing laparoscopic bariatric operations. Since the occurrence of RML in this patient population is relatively high, postoperative CK levels should be routinely obtained in patients at special risk.

[Antioxidant effects of L-arginine in the rat heart in experimental rhabdomyolysis].

The glycerol administration in a dose of 1 ml of 50% water solution/100 g b. w. was found to cause considerable accumulation of the total heme in the rat blood serum that is accompanied by an increase of TBA-reactive products and protein carbonyl derivates contents and by changes of protein level. Heme entering in the heart tissue is observed in the first hours after glycerol injection. The breaches of heart antioxidant-prooxidant balance are noted in twenty-four hours: TBA-reactive products and protein carbonyl derivates accumulation, heme oxygenase and catalase activation, superoxide dismutase activity lowering and reduction of glutathione content elevation. Pretreatment by L-arginine (0.5 h before glycerol administration) almost did not affect the blood serum changes caused by glycerol injection. However in the rat heart L-arginine administration prevents from TBA-reactive products and protein carbonyl derivates accumulation and the breaches of superoxide dismutase and catalase activities. Besides L-arginine causes the ealier heme oxygenase induction. Possible mechanisms of L-arginine protective action in the rat heart under experimental rhabdomyolysis are discussed.

[Antipsychotics and rhabdomyolysis. Differential diagnosis and clinical significance of elevated serum creatine kinase levels in psychiatric practice]. / Antipszichotikumok és rhabdomiolízis. A magas szérum kreatin-kináz érté k differenciáldiagnosztikája és klinikai jelentosége a pszichiátriai gyakorlatban.

INTRODUCTION: Elevated serum CK levels often occur in everyday psychiatric clinical practice. Although the majority of cases are benign and temporary, it is important to recognize and treat these conditions. METHOD: Review of the literature and case reports. RESULTS: The authors discuss the etiology, the clinical significance and the management of elevated serum creatine-kinase levels in psychiatric in-patient practice, focusing on antipsychotic-induced rhabdomyolysis. The authors also compare the pathogenesis, the clinical features and the treatment of neuroleptic malignant syndrome and rhabdomyolysis. A brief, practical guideline is introduced, which may help clinicians in the differential diagnosis and in the management of patients with elevated serum creatine kinase activity in emergent psychiatric practice. CONCLUSION: The most common etiologic factors (prescription drugs, alcohol, physical reasons, cardiac etiology) and clinical syndromes (rhabdomyolysis, neuroleptic malignant syndrome, acute coronary syndrome) should be considered, when elevated creatine kinase levels are encountered in psychiatric in-patients. Routine creatine kinase measurements in asymptomatic patients on antipsychotic medications are not recommended, but patients should be carefully followed for the development of rhabdomyolysis, when muscular symptoms arise. Cautiously challenging patients with another antipsychotic after an antipsychotic-induced rhabdomyolysis is recommended to decrease the possibility of recurrence. Careful monitoring of symptoms and potential complications is critical in order to avoid devastating clinical consequences.

IL6 (-174) and TNFA (-308) promoter polymorphisms are associated with systemic creatine kinase response to eccentric exercise.

Exertional rhabdomyolysis is a complex and poorly understood entity. The inflammatory system has an important role in muscle injury and repair. Serum creatine kinase (CK) is often used as systemic biomarker representing muscle damage. Considerable variation exists in CK response between different subjects. Genetic elements may act as predisposition factors for exertional rhabdomyolysis. Based on their biological activity, we hypothesized that in healthy subjects IL6 G-174C and TNFA G-308A promoter polymorphisms would be associated with CK response to exercise. We determined serum CK activity pre- and post-maximal eccentric contractions of the elbow flexor muscles. IL6 G-174C and TNFA G-308A genotypes were analyzed for possible relationship with changes in serum CK activity. IL6 G-174C genotype was associated with CK activity in a dose-dependent fashion. Subjects with one or more of the -174C allele had a greater increase and higher peak CK values than subjects homozygous for the G allele (mean +/- SE U/L: GG, 2,604 +/- 821; GC, 7,592 +/- 1,111; CC, 8,403 +/- 3,849, ANOVA P = 0.0003 for GG + GC genotypes versus CC genotype, P = 0.0005 for linear trend). IL6-174CC genotype was associated with a greater than threefold increased risk of massive CK response (adjusted odds ratio 3.29, 95% confidence interval 1.27-7.85, P = 0.009). A milder association (P = 0.06) was noted between TNFA G-308A genotype and CK activity. In conclusion, we found a strong association of the IL6 G-174C genotype with systemic CK response to strenuous exercise. Data suggest that homozygosity for the IL6-174C allele is a clinically important risk factor for exercise-induced muscle injury, further supporting the central role of cytokines in the reactive inflammatory process of muscle damage and repair.

Rhabdomyolysis and respiratory failure: rare presentation of carnitine palmityl-transferase II deficiency.

Carnitine palmityl-transferase (CPT) II deficiency is a rare disorder of the fatty acid beta-oxidation cycle. CPT II deficiency can be associated with rhabdomyolysis in particular conditions that increase the requirement for fatty acid oxidation, such as low-carbohydrate and high-fat diet, fasting, exposure to excessive cold, lack of sleep and prolonged exercise. The best known CPT II deficiency is the muscular form with episodic muscle necrosis and paroxysmal myoglobinuria after prolonged exercise. We report a case of a four-year-old male child, who, after one day of hyperthermia and fasting, developed a massive rhabdomyolysis beginning with acute respiratory failure and later complicated by acute renal failure. Appropriate management in Pediatric Intensive Care Unit (PICU) (mechanical ventilatory support, fluid supply combined with mannitol and bicarbonate infusions, administration of acetaminophen and antibiotics, and continuous venovenous haemofiltration) brought about complete resolution with an excellent outcome. Biochemical investigation of muscle biopsy and genetic analysis showed a deficiency of CPT II. The onset of CPT II deficiency with respiratory failure is extremely rare, but a correct and early diagnosis of rhabdomyolysis is the key to successful treatment. A metabolic myopathy such as CPT II deficiency should be suspected in children affected by rhabdomyolysis if trauma, crash, infections, drugs or extreme exertion can be excluded.

Validity of serum creatine kinase as a measure of muscle injury produced by lumbar surgery.

BACKGROUND AND PURPOSE: Serum creatine kinase (CK) concentrations have historically been used to investigate muscle disease and serious muscle damage, and there is a growing interest in the potential for a biochemical approach to quantifying skeletal muscle injury occurring in orthopedic surgeries and spinal injuries. The wide availability of CK measurement could foster spinal muscle injury research. However, measurement validity has never been systematically demonstrated in clinical settings. In this study, the validity of serum CK concentration elevation as an index of muscle injury was investigated using lumbar decompression surgery (LDS) as a model. SUBJECTS AND METHODS: Blood samples were obtained from 18 research volunteers drawn from the clinical population undergoing LDS. A baseline sample was taken in the preoperative waiting area. Each subject's highest CK concentration between 12 and 48 hours after surgery was used as the biochemical injury response. The surface area of muscle isolated (incision lengthxdepth) and strained by retraction was obtained for concurrent validity testing against biochemical measurement. RESULTS: The correlation between highest total CK concentration and muscle surface area was moderate (r=0.60) and significant (P<0.01). Correlations between surface area and CK at specific time points, revealed minimal loss of association at 12 hours (r=0.57) and 24 hours (r=0.58), but weaker correlations at 6 hours (r=0.45) and 48 hours (r=0.28) after injury. Analyses for proportions of each isoenzyme making up the total CK revealed that baseline and peak CK consisted almost exclusively of skeletal muscle CK (CK-MM), with minimal representation by heart muscle (CK-MB), and brain (CK-BB). CONCLUSIONS: The findings provide support for the validity of serum CK measurement as an index of skeletal muscle injury caused by LDS, and demonstrate that LDS provides a useful model for measurement testing and development studies.

Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatin.

We report a fatal case of toxic myopathy in a patient with a transplanted heart for severe ischemic coronary artery disease. He was on long-term cyclosporine, prednisone, and mycofenolate. Four months before the development of proximal muscle weakness, his simvastatin dose was doubled, and he was also started on colchicine for acute exacerbation of gout. He developed progressive muscle weakness leading to shortness of breath and hospitalization for respiratory failure. Colchicine and simvastatin were stopped on admission. He received high-dose methylprednisolone for continued muscle weakness while he was sedated with propofol. These changes led to a marked elevation of creatine kinase, peaking at 33,580 U/ml. The muscle biopsy revealed toxic vacuolization, mitochondrial damage, and no evidence of inflammation. Based on the timing of events, the combination of propofol, high-dose methylprednisolone, and cyclosporine have triggered rhabdomyolysis, which may have been facilitated by prior administration of colchicine and simvastatin.