Spurious hyperbicarbonatemia and a negative anion gap in a cat and a dog with severe rhabdomyolysis.

A 3-year-old male neutered domestic shorthair cat and a 2-year-old male neutered Labrador-mix dog were separately presented to the Veterinary Medical Center for evaluation after sustaining significant muscle trauma due to a dog attack and seizure activity, respectively. In both cases, biochemical analysis was consistent with rhabdomyolysis. Additionally, a markedly increased measured serum bicarbonate concentration and negative calculated anion gap were observed. As these biochemical abnormalities were not expected and deemed incompatible with life, an interference with the analyzer measurement of bicarbonate involving marked increases in pyruvate and lactate dehydrogenase (LDH) following myocyte injury was suspected. Venous blood gas analysis calculated bicarbonate concentration and anion gap were within reference interval, while measured LDH activity was markedly increased. These findings supported an analyzer-generated interference. This is the first published report of a previously described chemistry analyzer interference of markedly increased LDH activity with serum bicarbonate concentration measurement in dogs and cats. Awareness of this interference is important, particularly in the emergency setting, as it may influence case management.

MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated serum creatine kinase.

Striated muscle needs to maintain cellular homeostasis in adaptation to increases in physiological and metabolic demands. Failure to do so can result in rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals in six families from different ethnic backgrounds with biallelic variants in MLIP, which encodes the muscular lamin A/C-interacting protein, MLIP. Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels. The biallelic truncating variants were predicted to result in disruption of the nuclear localizing signal of MLIP. Additionally, reduced overall RNA expression levels of the predominant MLIP isoform were observed in patients' skeletal muscle. Collectively, our data increase the understanding of the genetic landscape of rhabdomyolysis to now include MLIP as a novel disease gene in humans and solidifies MLIP's role in normal and diseased skeletal muscle homeostasis.

Venous bicarbonate and creatine kinase as diagnostic and prognostic tools in the setting of acute traumatic rhabdomyolysis.

BACKGROUND: Myorenal or crush syndrome often develops following soft-tissue traumatic injury. It is a spectrum of disease that may result in severe renal dysfunction and kidney injury requiring renal replacement therapy. OBJECTIVES: To review a large cohort of patients with so-called myorenal or crush syndrome and assess the biochemical markers of venous bicarbonate and creatine kinase as predictors for the development of acute kidney injury (AKI). METHODS: All patients with myorenal syndrome who presented to Khayelitsha District Hospital, Cape Town, South Africa (SA), and Ngwelezana Hospital, Empangeni, KwaZulu-Natal, SA, between January and December 2017 were identified and reviewed. RESULTS: A total of 212 patients were included in the study. At both hospitals, 94% of the patients were male. Using the Pearson correlation coefficient, we compared creatinine kinase (CK) against serum creatinine. The mean CK level was 5 311.8 U/L and the mean creatinine level 133.457 µmol/L. The r-value was 0.2533. Although this is a technically positive correlation, the relationship between the variables is weak. Using the Pearson R Calculator, we inserted the r-value to calculate the p-value. The p-value was 0.000208. When comparing venous bicarbonate (HCO3) against creatinine, the mean HCO3 level was 22.296 mmol/L and the mean creatinine level 162.053 µmol/L. The r-value was -0.3468. Although this is a technically negative correlation, the relationship between the variables is weak. Using the Pearson R Calculator, we inserted the r-value to calculate the p-value. The p-value was 0.000013. The inverse ratio shown with HCO3 v. creatinine, although still a weak correlation, is significantly better in predicting an increase in creatinine compared with the weak positive correlation of CK v. creatinine. CONCLUSIONS: Although both venous HCO3 and CK showed a weak correlation with creatinine, the former performed significantly better in predicting AKI. In a resource-constrained system, we recommend that HCO3 be measured to assess patients with crush injury and that CK be regarded as a complementary modality.

Rhabdomyolysis in Severe COVID-19: Male Sex, High Body Mass Index, and Prone Positioning Confer High Risk.

BACKGROUND: Bedside experience and studies of critically ill patients with coronavirus disease 2019 (COVID-19) indicate COVID-19 to be a devastating multisystem disease. We aim to describe the incidence, associated variables, and outcomes of rhabdomyolysis in critically ill COVID-19 patients. MATERIALS AND METHODS: Data for all critically ill adult patients (≥18 years old) admitted to the ICU at a large academic medical center with confirmed COVID-19 between March 13, 2020 and April 18, 2020 were prospectively collected. Patients with serum creatine kinase (CK) concentrations greater than 1000 U/L were diagnosed with rhabdomyolysis. Patients were further stratified as having moderate (serum CK concentration 1000-4999 U/L) or severe (serum CK concentration ≥5000 U/L) rhabdomyolysis. Univariate and multivariate analyses were performed to identify outcomes and variables associated with the development of rhabdomyolysis. RESULTS: Of 235 critically ill COVID-19 patients, 114 (48.5%) met diagnostic criteria for rhabdomyolysis. Patients with rhabdomyolysis more often required mechanical ventilation (P < 0.001), prone positioning (P < 0.001), pharmacological paralysis (P < 0.001), renal replacement therapy (P = 0.010), and extracorporeal membrane oxygenation (ECMO) (P = 0.025). They also had longer median ICU length of stay (LOS) (P < 0.001) and hospital LOS (P < 0.001). No difference in mortality was observed. Male sex, patients with morbid obesity, SOFA score, and prone positioning were independently associated with rhabdomyolysis. CONCLUSIONS: Nearly half of critically ill COVID-19 patients in our cohort met diagnostic criteria for rhabdomyolysis. Male sex, morbid obesity, SOFA score, and prone position were independently associated with rhabdomyolysis.

Circulating microRNAs after a 24-h ultramarathon run in relation to muscle damage markers in elite athletes.

Ultra-endurance sports are growing in popularity but can be associated with adverse health effects, such as exercise-induced muscle damage (EIMD), which can lead to exertional rhabdomyolysis. Circulating microRNAs (miRNAs) may be useful to approach the degree of EIMD. We aimed to (1) investigate the relevance of circulating miRNAs as biomarkers of muscle damage and (2) examine the acute response of skeletal/cardiac muscle and kidney biomarkers to a 24-h run in elite athletes. Eleven elite athletes participated in the 24-h run World Championships. Counter-movement jump (CMJ), creatine kinase (CK), myoglobin (Mb), creatinine (Cr), high-sensitive cardiac troponin T (hs-cTnT), and muscle-specific miRNA (myomiR) levels were measured before, immediately after, and 24 and 48h after the race. CMJ height was reduced immediately after the race (-84.0 ± 25.2%, p < 0.001) and remained low at 24 h (-43.6 ± 20.4%, p = 0.002). We observed high CK activity (53 239 ± 63 608 U/L, p < 0.001) immediately after the race, and it remained elevated 24h after (p < 0.01). Circulating myomiR levels (miR-1-3p, miR-133a-3p, miR-133b, miR-208a-3p, miR-208b-3p, and miR-499a-5p) were elevated immediately after the 24-h run (fold changes: 18-124,723, p<0.001) and significantly (p < 0.05) correlated or tended to significantly (p < 0.07) correlate with the reduction in CMJ height at 24 h. We found no significant correlation between CMJ height loss at 24 h and CK (p = 0.23) or Mb (p = 0.41) values. All elite ultramarathon runners included in our study were diagnosed with exertional rhabdomyolysis after the 24-h ultramarathon race. MyomiR levels may be useful to approach the degree of muscle damage.

Severe rhabdomyolysis induced by possible drug-drug interaction between Ribociclib and Simvastatin.

INTRODUCTION: Drug-drug interactions with cyclin-dependent kinases inhibitors 4 and 6 (CDK4/6) are known and should be taken into account. CASE REPORT: A 68-year-old woman, on prior Simvastatin therapy, developed severe rhabdomyolysis after three weeks of Ribociclib initiation. She showed general weakness with mobility problems and was admitted to our hospital. MANAGEMENT AND OUTCOME: Ribociclib and Simvastatin were discontinued and the patient received intensive intravenous hydration. She finally recovered her mobility after two weeks. DISCUSSION: We hypothesize that Simvastatin induced rhabdomyolysis by possible interaction with Ribociclib. Ribociclib is a strong inhibitor of CYP 3A4 and a potential inhibitor of OATP1B1 membrane transporter. Simvastatin plasma concentration may reach toxic levels due to Ribociclib inhibition. To assess the relevance of our hypothesis, we used the Drug Interaction Scale. With a total score of 7, the interaction is considered as "probable." Because of the high risk of severe rhabdomyolysis, the concomitant use of Simvastatin with Ribociclib should be avoided or otherwise careful monitoring of creatine kinase is warranted.

Electrical weapons and rhabdomyolysis.

It has been suggested that an application of a conducted electrical weapon (CEW) might cause muscle injury such as rhabdomyolysis and an acute inflammatory response. We explored this hypothesis by testing the effects of electrical weapons on circulating markers of inflammation and muscle damage. In a prospective study, 29 volunteers received a full-trunk 5-s TASER® X26(E) CEW exposure. Venous blood samples were taken before, 5 min after, and at 24 h following the discharge. We tested for changes in serum levels of C-reactive protein (CRP), alkaline phosphatase (ALP), myoglobin, albumin, globulin, albumin/globulin ratio, aspartate and alanine aminotransferase, creatine kinase, total protein, bilirubin, and lactic acid dehydrogenase. Uncorrected CRP and myoglobin levels were lower in the immediate post exposure period (CRP levels 1.44 ± 1.39 v 1.43 ± 1.32 mg/L; p = 0.046 and myoglobin 36.8 ± 11.9 v 36.1 ± 13.9 µg/L; p = 0.0019) but these changes were not significant after correction for multiple comparisons. There were no changes in other biomarkers. At 24 h, CRP levels had decreased by 30% to 1.01 ± 0.80 mg/L (p = 0.001 from baseline). ALP was unchanged immediately after the CEW application but was reduced by 5% from baseline (66.2 ± 16.1 to 62.7 ± 16.1 IU/L; p = 0.0003) at 24 h. No other biomarkers were different from baseline at 24 h. A full-trunk electrical weapon exposure did not lead to clinically significant changes in the acute phase protein levels or changes in measures of muscle cellular injury. We found no biomarker evidence of rhabdomyolysis.

Rhabdomyolysis in Patients Hospitalized With COVID-19 Infection: Five Case Series.

The novel SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2) is now known to cause acute respiratory distress, cytokine storm, and coagulopathy. Multiple other manifestations have been published in recent literature. Rhabdomyolysis is a syndrome of muscle damage, with release of intracellular contents into circulation. It is characterized by marked elevations of creatinine kinase levels and myoglobinuria. In this article, we describe a series of 5 cases who were admitted with COVID-19 pneumonia and had severe muscle injury, as demonstrated by significant elevation (>5 times upper limit of normal) of creatinine kinase levels likely secondary to SARS-CoV-2 virus. The median age for these patients was 65 years, and most of them suffered from diabetes and hyperlipidemia. All patients were hypertensive males. Four out of 5 patients had preserved kidney function at baseline and were chronic kidney disease (CKD) stage 2 or better. However, most of them suffered significant kidney injury and at the time of discharge one patient was CKD stage 2 or better, 2 were CKD stage 3 or worse, and 2 patients had renal failure and died due to complications of SARS-CoV-2 infection.

Electromuscular Incapacitation Current Induced Neuromuscular Tissue Injury.

Electrical stun devices (ESDs) serve a basic role in law enforcement and provide an alternative to lethal options for target control by causing electromuscular incapacitation (EMI). A fundamental concern is the adverse health consequences associated with their use. The capability of EMI electric field pulses to disrupt skeletal muscle cells (i.e. rhabdomyolysis) was investigated over the operational range commonly used in commercial EMI devices. Functional and structural alteration and recovery of muscle and nerve tissue were assessed. In an anesthetized swine model, the left thigh was exposed to 2 min of electrical pulses, using a commercially available ESD or a custom-made EMI signal power amplifier. Serum creatinine phosphokinase (CPK), troponin, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels were monitored intermittently for 6 h post-EMI exposure. A standard external cardiac defibrillator served as a positive control. Muscle and nerve tissue histology adjacent to the EMI contacts were examined. Post-EMI shock skeletal muscle function was evaluated by analyzing the compound muscle action potentials (CMAPs) of the rectus femoris muscle. Maximal energy cardiac defibrillator pulses resulted in rhabdomyolysis and marked elevation of CPK, LDH, and AST 6 h post-shock. EMI field pulses resulted in the animals developing transient acidosis. CMAP amplitudes decreased approximately 50% after EMI and recovered to near-normal levels within 6 h. Within 6 h post-EMI exposure, blood CPK was mildly increased, LDH was normal, and no arrhythmia was observed. Minimal rhabdomyolysis was produced by the EMI pulses. These results suggest that EMI exposure is unlikely to cause extremity rhabdomyolysis in normal individuals. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

Effects of fasting, feeding and exercise on plasma acylcarnitines among subjects with CPT2D, VLCADD and LCHADD/TFPD.

BACKGROUND: The plasma acylcarnitine profile is frequently used as a biochemical assessment for follow-up in diagnosed patients with fatty acid oxidation disorders (FAODs). Disease specific acylcarnitine species are elevated during metabolic decompensation but there is clinical and biochemical heterogeneity among patients and limited data on the utility of an acylcarnitine profile for routine clinical monitoring. METHODS: We evaluated plasma acylcarnitine profiles from 30 diagnosed patients with long-chain FAODs (carnitine palmitoyltransferase-2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD), and long-chain 3-hydroxy acyl-CoA dehydrogenase or mitochondrial trifunctional protein (LCHAD/TFP) deficiencies) collected after an overnight fast, after feeding a controlled low-fat diet, and before and after moderate exercise. Our purpose was to describe the variability in this biomarker and how various physiologic states effect the acylcarnitine concentrations in circulation. RESULTS: Disease specific acylcarnitine species were higher after an overnight fast and decreased by approximately 60% two hours after a controlled breakfast meal. Moderate-intensity exercise increased the acylcarnitine species but it varied by diagnosis. When analyzed for a genotype/phenotype correlation, the presence of the common LCHADD mutation (c.1528G > C) was associated with higher levels of 3-hydroxyacylcarnitines than in patients with other mutations. CONCLUSIONS: We found that feeding consistently suppressed and that moderate intensity exercise increased disease specific acylcarnitine species, but the response to exercise was highly variable across subjects and diagnoses. The clinical utility of routine plasma acylcarnitine analysis for outpatient treatment monitoring remains questionable; however, if acylcarnitine profiles are measured in the clinical setting, standardized procedures are required for sample collection to be of value.

Creatine kinase elevation after robotic surgery for rectal cancer due to a prolonged lithotomy position.

BACKGROUND: Robotic surgery for rectal cancer, which is now performed worldwide, can be associated with elevated creatine kinase levels postoperatively. In this study, we compared postoperative complications between patients undergoing robotic surgery and laparoscopic surgery. METHODS: We identified 66 consecutive patients who underwent curative resection for rectal cancer at Juntendo University Hospital between January 2016 and February 2019. Patients were divided into a conventional laparoscopic surgery (CLS) group (n = 38) and a robotic-assisted laparoscopic surgery (RALS) group (n = 28) before comparing various clinicodemographic factors between the groups. RESULTS: Patient age and gender, surgical approach (CLS/RALS), pathological T factor, pathological stage, duration of postoperative hospital stay, and postoperative complications were not significantly different between the RALS and CLS groups. However, the operation time was significantly longer in the RALS group (407 min) than in the CLS group (295 min; p < 0.001). Notably, the serum level of creatine kinase on postoperative day 1 was significantly higher in the CLS group (154 IU/L) than in the RALS group (525 IU/L; p < 0.001), despite there being no significant differences in the incidence of rhabdomyolysis. The multivariate analysis showed that RALS/CLS (HR 6.0 95% CI 1.3-27.5, p = 0.02) and operation time (HR 15.9 95% CI 3.79-67.4, p = 0.001) remained independent factors of CK elevation on postoperative day 1. CONCLUSIONS: Clinically relevant positioning injuries and rhabdomyolysis may occur in patients who are subjected to a prolonged and extreme Trendelenburg position or who have extra force applied to the abdominal wall because of remote center displacement. The creatine kinase value should therefore be measured after RALS to monitor for the sequelae of these potential positioning injuries.

Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments.

Serum activities of alanine and aspartate aminotransferases (ALT and AST) are used as gold standard biomarkers for the diagnosis of hepatocellular injury. Since ALT and AST lack liver specificity, the diagnosis of the onset of hepatocellular injury in patients with underlying muscle impairments is severely limited. Thus, we evaluated the potential of glutamate dehydrogenase (GLDH) as a liver specific alternative biomarker of hepatocellular injury. In our study, serum GLDH in subjects with Duchene muscular dystrophy (DMD) was equivalent to serum GLDH in age matched healthy subjects, while serum ALT was increased 20-fold in DMD subjects. Furthermore, serum GLDH in 131 subjects with variety of muscle impairments was similar to serum GLDH of healthy subjects while serum ALT corelated with serum creatine kinase, a widely accepted biomarker of muscle impairment. In addition, significant elevations of ALT, AST, and CK were observed in a case of a patient with rhabdomyolysis, while serum GLDH stayed within the normal range until the onset of hypoxia-induced liver injury. In a mouse model of DMD (DMDmdx), serum GLDH but not serum ALT clearly correlated with the degree of acetaminophen-induced liver injury. Taken together, our data support the utility of serum GLDH as a liver-specific biomarker of liver injury that has a potential to improve diagnosis of hepatocellular injury in patients with underlying muscle impairments. In drug development, GLDH may have utility as a biomarker of drug induced liver injury in clinical trials of new therapies to treat muscle diseases such as DMD.

Pediatric COVID-19-associated rhabdomyolysis: a case report.

COVID-19 is the illness caused by infection with the novel coronavirus SARS-CoV-2. Although myalgia is common in adults, it has not been noted as a common symptom in children. There have been a few reported cases of COVID-19-associated rhabdomyolysis in adults. This case report describes a 16-year-old boy who presented with fever, myalgias, mild shortness of breath with exertion, and dark-colored urine. COVID-19 PCR was positive. His initial creatinine kinase (CK) level was 427,656 U/L. Serum creatinine was normal for age. He was treated with isotonic intravenous fluids containing sodium bicarbonate to maintain urine output of 100-200 mL/h and urine pH > 7.0. His serum creatinine remained normal throughout the hospital stay and he was discharged on hospital day 12 with a CK of 6526 U/L. To our knowledge, no pediatric cases of COVID-19-associated rhabdomyolysis have been previously reported. Adult cases of rhabdomyolysis have been reported and a few reports have noted patients with elevated CK levels without rhabdomyolysis. Given this pediatric case of COVID-19-associated rhabdomyolysis, pediatric clinicians should be aware of this complication and manage fluids appropriately in order to prevent acute kidney injury.

Abnormal liver function tests associated with severe rhabdomyolysis.

Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium, phosphate, urate and intracellular proteins such as myoglobin into the circulation, which may cause complications including acute kidney injury, electrolyte disturbance and cardiac instability. Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis. Typically, there is an increase in serum aminotransferases, namely aspartate aminotransferase and alanine aminotransferase. This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy. However, muscle can also be a source of the increased aminotransferase activity. This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association. It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases, and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury. Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury. This review also explores potential approaches to improve the accuracy of our diagnostic tools, so that excessive or unnecessary liver investigations can be avoided.

Exercise-Induced Muscle Damage and Cardiac Stress During a Marathon Could be Associated with Dietary Intake During the Week Before the Race.

: Adequate food intake is important prior to endurance running competitions to facilitate adequate exercise intensity. However, no investigations have examined whether dietary intake could prevent exercise-induced muscle damage (EIMD) and cardiac stress (EICS). Thus, this study's objective was to determine the associations between EIMD, EICS and endurance athlete diets one week before a marathon race. Sixty-nine male runners participated in this study. Food intake during the week prior to the race was collected through a seven-day weighed food record. Dietary intake on race day was also recorded. At the end of the marathon, blood samples were drawn to determine serum creatine kinase (CK) and myoglobin, and muscle-brain isoform creatine kinase (CK-MB), prohormone of brain natriuretic peptide (NT-proBNP), cardiac troponin I (TNI), and cardiac troponin T (TNT) concentration as markers of EIMD and EICS, respectively. To determine the association between these variables, a stepwise regression analysis was carried out. The dependent variable was defined as EIMD or EICS and the independent variables were defined as the number of servings within each different food group. Results showed that the intake of meat during the previous week was positively associated with post-race CK (Standardized Coefficients (ß) = 0.643; p < 0.01) and myoglobin (ß = 0.698; p < 0.001). Vegetables were negatively associated the concentration of post-race CK (ß = -0.482; p = 0.002). Butter and fatty meat were positively associated with NT-proBNP (ß = 0.796; p < 0.001) and TNI (ß = 0.396; p < 0.001) post-marathon values. However, fish intake was negatively associated with CK (ß = -0.272; p = 0.042), TNI (ß = -0.593; p < 0.001) and TNT (ß = -0.640; p = 0.002) post-marathon concentration. Olive oil was negatively associated with TNI (ß = -0.536; p < 0.001) and TNT (ß = -0.415; p = 0.021) values. In conclusion, the consumption of meat, butter, and fatty meat might be associated with higher levels of EIMD and EICS. On the other hand, fish, vegetables, and olive oil might have a protective role against EIMD and EICS. The selection of an adequate diet before a marathon might help to reduce some of the acute burdens associated with marathon races.