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.

Repeated and progressive rhabdomyolysis due to a novel carnitine palmitoyltransferase II gene variant in an adult male: A case report.

INTRODUCTION: The occurrence of repeated and progressive rhabdomyolysis is rare in clinical settings, particularly in adults. The pathogenesis of rhabdomyolysis is often overlooked due to its rapid recovery. Carnitine palmitoyltransferase (CPT) II deficiency could be a rare etiology of repetitive nontraumatic rhabdomyolysis, and several mutations of CPT II have been reported. PATIENT CONCERNS: A 41-year-old man presented with high fever, general malaise, myalgia, dyspnea, and dark-colored urine, and then progressed to anuria. In the past 15 years, he experienced dark-colored urine twice due to exercise and high fever. Physical examination revealed oliguria, suppurated tonsils, poor hemoglobin saturation, alert consciousness, normal neurological signs and reflexes, hypertension, and tachypnea. Laboratory investigations showed positive test results for inflammation, high serum myogenic enzyme levels, and evidence of acute kidney injury (AKI). DIAGNOSES: Investigations revealed an extremely high serum myogenic enzyme levels and impaired renal function with serum creatinine level of 510 µmol/L, consistent with the diagnosis of rhabdomyolysis, AKI stage 3, and acute respiratory distress syndrome. High levels of acylcarnitine in the serum confirmed the diagnosis of CPT II deficiency. In addition, whole exome sequencing (WES) was conducted in the patient and his mother. INTERVENTIONS: Intubation, ventilator support, and hemodialysis were the major therapeutic interventions at the peak of disease progression. He was then administered valsartan tablets at a dosage of 80 mg per day and L-carnitine supplements. OUTCOMES: WES conducted in the patient and his mother revealed 2 novel mutations of CPT II (c.482G>A and c.1493G>T) in this patient. The patient recovered from the severe AKI but the renal function remained impaired at chronic kidney disease stage 3a. CONCLUSION: Thus, gene examination can help to understand the etiology of repetitive nontraumatic rhabdomyolysis. Accurate diagnosis can be beneficial for providing an individualized treatment for patients with repeated and progressive rhabdomyolysis.

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate.

BACKGROUND: Heat stress and rhabdomyolysis are major risk factors for the occurrence of repeated acute kidney injury in workers exposed to heat and strenuous work. These episodes, in turn, may progress to chronic kidney disease. OBJECTIVE: The purpose of this study was to test the effect of allopurinol (AP) and sodium bicarbonate on the kidney injury induced by recurrent heat stress dehydration with concomitant repeated episodes of rhabdomyolysis. METHODS: The model consisted of heat stress exposure (1 h, 37°C) plus rhabdomyolysis (R) induced by repetitive IM injections of glycerol (7.5 mL/kg BW days) in the rat. In addition, to replicate the human situation, uricase was inhibited (oxonic acid [OA] 750 mg/K/d) to increase uric acid (UA) levels. Additional groups were treated either with AP 150 mg/L, n = 10, bicarbonate (BC; 160 mM, n = 10), or both (AP + BC, n = 10) in drinking water. We also included 2 control groups consisting of normal controls (N-Ref, n = 5) and uricase-inhibited rats (OA, n = 5) that were not exposed to heat or muscle injury. Groups were studied for 35 days. RESULTS: Uricase-inhibited rats exposed to heat and rhabdomyolysis developed pathway and increased intrarenal oxidative stress and inflammasome activation. Kidney injury could be largely prevented by AP, and also BC, although the treatments were not synergistic. CONCLUSION: Increased levels of UA may play an important role in the renal alterations induced by heat stress and continuous episodes of rhabdomyolysis. Therefore, treatments aimed to reduce hyperuricemia may help to decrease the renal burden in these conditions. Clinical trials are suggested to test whether this is also true in humans.

Therapeutic Effects of Procainamide on Endotoxin-Induced Rhabdomyolysis in Rats.

Overt systemic inflammatory response is a predisposing mechanism for infection-induced skeletal muscle damage and rhabdomyolysis. Aberrant DNA methylation plays a crucial role in the pathophysiology of excessive inflammatory response. The antiarrhythmic drug procainamide is a non-nucleoside inhibitor of DNA methyltransferase 1 (DNMT1) used to alleviate DNA hypermethylation. Therefore, we evaluated the effects of procainamide on the syndromes and complications of rhabdomyolysis rats induced by lipopolysaccharide (LPS). Rhabdomyolysis animal model was established by intravenous infusion of LPS (5 mg/kg) accompanied by procainamide therapy (50 mg/kg). During the experimental period, the changes of hemodynamics, muscle injury index, kidney function, blood gas, blood electrolytes, blood glucose, and plasma interleukin-6 (IL-6) levels were examined. Kidneys and lungs were exercised to analyze superoxide production, neutrophil infiltration, and DNMTs expression. The rats in this model showed similar clinical syndromes and complications of rhabdomyolysis including high levels of plasma creatine kinase, acute kidney injury, hyperkalemia, hypocalcemia, metabolic acidosis, hypotension, tachycardia, and hypoglycemia. The increases of lung DNMT1 expression and plasma IL-6 concentration were also observed in rhabdomyolysis animals induced by LPS. Treatment with procainamide not only inhibited the overexpression of DNMT1 but also diminished the overproduction of IL-6 in rhabdomyolysis rats. In addition, procainamide improved muscle damage, renal dysfunction, electrolytes disturbance, metabolic acidosis, hypotension, and hypoglycemia in the rats with rhabdomyolysis. Moreover, another DNMT inhibitor hydralazine mitigated hypoglycemia, muscle damage, and renal dysfunction in rhabdomyolysis rats. These findings reveal that therapeutic effects of procainamide could be based on the suppression of DNMT1 and pro-inflammatory cytokine in endotoxin-induced rhabdomyolysis.

Fat burn X: burning more than fat.

A 50-year-old man presented with a 2-day history of bilateral lower extremity cramping and dark urine. The patient was found to have a creatine phosphokinase (CPK) elevated of up to 2306 U/L, a serum uric acid of 9.7 mg/dL and 101 red blood cell's per high-powered field on urinalysis. On questioning, the patient endorsed daily exercise with free weights. There were no changes in his regular exercise and medication regimen, no muscle trauma, no recent drug use and no illness. The patient did mention using a new fat burner known as 'Fat Burn X', which he had begun taking 2 days prior to the onset of his muscle cramps. The patient was given normal saline intravenous fluid resuscitation for 48 h with resultant normalisation of his CPK and creatinine, and was discharged with primary care follow-up.

Risk identification and possible countermeasures for muscle adverse effects during statin therapy.

The use of statins for cardiovascular disease prevention is clearly supported by clinical evidence. However, in January 2014 the U.S. Food and Drug Administration released an advice on statin risk reporting that "statin benefit is indisputable, but they need to be taken with care and knowledge of their side effects". Among them the by far most common complication is myopathy, ranging from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. This class side effect appears to be dose dependent, with more lipophilic statin (i.e., simvastatin) carrying a higher overall risk. Hence, to minimize statin-associated myopathy, clinicians should take into consideration a series of factors that potentially increase this risk (i.e., drug-drug interactions, female gender, advanced age, diabetes mellitus, hypothyroidism and vitamin D deficiency). Whenever it is appropriate to stop statin treatment, the recommendations are to stay off statin until resolution of symptoms or normalization of creatine kinase values. Afterwards, clinicians have several options to treat dyslipidemia, including the use of a lower dose of the same statin, intermittent non-daily dosing of statin, initiation of a different statin, alone or in combination with nonstatin lipid-lowering agents, and substitution with red yeast rice.

Rhabdomyolysis and acute kidney injury after acupuncture sessions.

Rhabdomyolysis is usually caused by muscle injury, drugs or alcohol and presents with muscle weakness and pain. It is characterized by rise in serum creatine kinase, aminotransferases and electrolytes as well as myoglobinuria. Myoglobinuria may cause acute kidney injury by direct proximal tubule cytotoxicity, renal vasoconstriction, intraluminal cast formation and distal tubule obstruction. Muscle pain and weakness as well as vascular injury have been reported after acupuncture. We report a case of severe rhabdomyolysis and acute kidney injury after acupuncture sessions.

Pretreatment with hydrogen-rich saline reduces the damage caused by glycerol-induced rhabdomyolysis and acute kidney injury in rats.

BACKGROUND: Rhabdomyolysis is a leading cause of acute kidney injury. The pathophysiological process involves oxidative stress and inflammation. Hydrogen-rich saline (HRS) is an antioxidant and anti-inflammatory. This study explored the protective effect of pretreatment with HRS on the development of glycerol-induced rhabdomyolysis acute kidney injury. MATERIALS AND METHODS: Forty-eight rats were randomly divided into four equal groups. Group 1 served as the control, group 2 was given 50% glycerol (10 mL/kg, intramuscular), group 3 was given glycerol after 7 d pretreatment with high dose HRS (10 mL/kg/d, intraperitoneal), and group 4 was given glycerol after 7 d pretreatment with low dose HRS (5 mL/kg/d, intraperitoneal). Renal health was monitored by serum creatinine (Cr), urea, and histologic analysis; rhabdomyolysis was monitored by creatine kinase (CK) levels; and oxidative stress was monitored by kidney tissue reactive oxygen species (ROS), malondialdehyde, 8-hydroxydeoxyguanosine (8-OH-dG), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) levels. Inflammation was monitored by interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) evaluation. RESULTS: Glycerol administration resulted in an increase in the mean histologic damage score, serum Cr, urea and CK, kidney tissue ROS, malondialdehyde, 8-OH-dG, GSH-PX, IL-6, and TNF-α, and a decrease in kidney tissue superoxide dismutase activity. All these factors were significantly improved by both doses of HRS, but the mean histologic damage score, urea, Cr, CK, ROS, 8-OH-dG, GSH-PX, IL-6, and TNF-α for the high dose HRS treatment group were even lower. CONCLUSIONS: Pretreatment by HRS ameliorated renal dysfunction in glycerol-induced rhabdomyolysis by inhibiting oxidative stress and the inflammatory response.

Hydroxycut weight loss dietary supplements: a contributing factor in the development of exertional rhabdomyolysis in three U.S. Army soldiers.

Exertional rhabdomyolysis is an enigmatic syndrome with multiple risk factors and a wide spectrum of clinical outcomes. Dietary supplements containing caffeine may potentiate the rhabdomyolysis cascade, and present an area of attainable prevention. Presented are three cases of soldiers using the weight loss supplement brand, Hydroxycut; patient education regarding caffeine and supplement safety may shield against morbidity and delayed soldier readiness associated with overcaffeination.

Selective serotonin reuptake inhibitors and rhabdomyolysis after eccentric exercise.

PURPOSE: The purpose of this report was to review three cases of clinically significant rhabdomyolysis that developed in research subjects after completing an eccentric exercise protocol. All three cases occurred in subjects who reported use of selective serotonin reuptake inhibitors (SSRI). METHODS: Sixty-three subjects enrolled in the study. Subjects performed 15 sets of 15 repetitions of maximal eccentric contractions of the elbow flexors. Subjects were then monitored on a daily basis for development of delayed onset muscle soreness (DOMS). Subjects received either microcurrent electrical neuromuscular stimulation (MENS) or sham treatment. RESULTS: Three subjects developed clinically significant rhabdomyolysis after performing this exercise protocol. Affected subjects were the only subjects who reported use of SSRI during the study period. CONCLUSION: This report raises suspicion of SSRI use as a predisposing factor to muscle injury after eccentric exercise.

Hyperbaric oxygen as an adjunctive therapy for bilateral compartment syndrome, rhabdomyolysis and acute renal failure after heroin intake.

Heroin abuse causes various medical and surgical complications. We report a case of heroin-induced severe bilateral compartment syndrome complicated by rhabdomyolysis, acute renal failure and extremely elevated creatinine kinase. A 30-year-old male heroin addict presented to the emergency department of Mount Vernon Hospital, Mount Vernon, New York complaining of severe pain and burning sensation in both legs and feet 1 day after abusing intravenous heroin. He had severe swelling and tenderness of both legs and feet. Laboratory data revealed tremendous elevation of creatine kinase (236,000 IU/L) consistent with rhabdomyolysis. Acute renal failure developed over subsequent days. Treatment consisted of fasciotomy, hyperbaric oxygen therapy (HBO2) and supportive therapy. The condition gradually improved over 4 weeks and the patient did not require dialysis or amputation.

Disturbance of consciousness associated with hypophosphatemia in a chronically alcoholic patient.

A 69-year-old man with chronic alcoholism was admitted to our hospital due to disturbance of consciousness and oliguria. Emergency laboratory examination revealed metabolic acidosis, hypoglycemia, hyponatremia, mild liver dysfunction, acute renal failure and rhabdomyolysis. After administration of fluids and nutrients and continuous hemodiafiltration, he recovered from all signs and symptoms except for disturbance of consciousness after 7 days. Since severe hypophosphatemia persisted, we administered adequate phosphates, and then his level of consciousness normalized. We discuss the relationships among alcohol abuse, hypophosphatemia and disturbance of consciousness, and recommend that hypophosphatemia be considered a potential cause of disturbance of consciousness in alcoholic patients.

[Assessment of regional and systemic toxicity of isolated hyperthermic extremity perfusion with tumor necrosis factor-alpha and melphalan]. / Erfassung regionaler und systemischer Toxizität der isolierten, hyperthermen Extremitätenperfusion mit Tumor-Nekrose-Faktor alpha und Melphalan.

Following isolated limb perfusion (ILP) with TNF alpha and melphalan the damage to muscle tissue and its systemic consequences in terms of myoglobinemia and myoglobinuria as well as the activation of the cytokine cascade were investigated. We measured the compartmental pressure of the limb during and after perfusion and determined the serum changes of myoglobin, creatine kinase (CK), interleukin (IL)-6, IL-1, s-IL-2-receptor, TNF-receptor, and ICAM-1 levels. The compartmental pressure rose significantly during ILP and decreased after reperfusion. Following its course, the decision whether to perform a fasciotomy or not can be more reliably made. Serum myoglobin levels exceeded 200 times normal values and the increase occurred significantly earlier than that of CK, thus enabling judgement of the risk of renal failure (crush kidney syndrome). The elevation of serum IL-1 and IL-6 values correlated with the frequency of cardiopulmonary problems (hyperdynamic shock) and facilitated counter-maneuvers. Our data, although obtained from ILP with TNF alpha, could be used to monitor toxicity also when other drug regimens are administered.

[Severe hypercalcemia after rhabdomyolysis and acute renal failure]. / Hypercalcémie grave après rhabdomyolyse et insuffisance rénale aiguë.

Two cases of rhabdomyolysis with renal failure followed by hypercalcaemia are reported. Both had major hyperphosphataemia and hypocalcaemia, requiring haemodialysis. Hypercalcaemia developed during the diuretic phase, when renal function was still abnormal, and before phosphate blood levels had returned to normal. Soft tissue calcifications occurred in one of the patients. The pathogenesis and treatment of this condition are discussed. Increased levels of serum calcitriol may play an important role in the genesis of hypercalcaemia, which may last for several months. Giving calcium salts and or vitamin D to these patients during the hypocalcaemic phase is dangerous, and should be avoided. The usual treatment for hypercalcaemia my remain ineffective. Mithramycin can lower the serum calcium concentration but the new diphosphonates (sodium etidronate) are very effective in the treatment of this hypercalcaemia. However, in serious or urgent cases, hypocalcaemic haemodialysis may be required, with the simultaneous administration of calcitonin and diphosphonates.

Some factors influencing plasma AST/CK activities in thoroughbred racehorses.

Sixty-six Thoroughbred horses in training (2 or 3 years of age) were studied during one flat racing season, to investigate the relationship between age, sex, time of year, dietary electrolyte imbalances and plasma aspartate aminotransferase/creatine kinase (AST/CK) activities. Management and training variations were minimised. Between February to October, monthly 24 h post exercise samples were collected and analysed for AST and CK activities. Sex and/or age were shown to have a significant effect on the occurrence of high CK (> 100 iu/litre) and AST (> 300 iu/litre) activities. Fillies were more likely to have elevated CK and AST than colts. Two-year-olds tended to have higher AST activities than three-year-olds. Time of year had no significant effect on the number of animals with high or low activities. Fourteen animals had consistently raised plasma AST activities (median > 300 iu/litre). Eight of these raced and seven won at least one race. The average daily intake of calcium, sodium, phosphorus and potassium was determined at each sampling time. In eight of the horses, the fractional electrolyte excretion (FE) of phosphate (PO4) and sodium (Na) was determined monthly. FE values were also determined in three horses which had suffered repeated attacks of the equine rhabdomyolysis syndrome. The FE, PO4 and Na values reflected dietary intake of calcium, phosphorus and sodium respectively. It was not possible to determine any effect of training or a predisposition to equine rhabdomyolysis. No obvious differences were found between the resting thyroxine values of three animals with consistently low AST activities, six of those with consistently raised AST and three animals which had suffered repeated attacks of rhabdomyolysis.

[Pre- and postoperative evaluation of plasma creatine kinase in 142 children subjected to "uncomplicated" anesthesia in muscle biopsy]. / Valutazione pre e postoperatoria della creatinkinasi plasmatica in 142 bambini sottoposti "senza complicazioni" ad anestesia per biopsia muscolare.

Pre- and postoperative serum CK activity is evaluated in 142 children submitted, "uneventfully", to diagnostic muscle biopsy under halothane (77 patients), ketamine (50 patients) or "local" (15 patients) anaesthesia. The purpose was to ascertain whether or not anaesthesia-induced-rhabdomyolysis (AR) was an asymptomatic (and unrecognized) complication of "uneventful" anaesthesia. The majority of patients with low preoperative CK values showed a slight increase of serum CK activity on the first postoperative day. On the contrary, a postoperative decrease was observed in the majority of patients with high preoperative values (namely in almost all ketamine patients and in 2/3 of halothane-patients). In no case postoperative increase reached a value suggesting the occurrence of AR even though a postoperative value of 16480 U/I was observed in a patient with Duchenne muscular dystrophy after halothane anaesthesia. Sudden interruption of motor activity induced by general anaesthesia seems to be the most important factor in reducing the release of CK from muscle. When preoperative release is low, any further postoperative reduction is not sufficient to balance the moderate increase of CK produced by the surgical procedure; the opposite should happen in patients presenting with high preoperative release. So far as anaesthetics are concerned, our data seem to suggest that ketamine has a higher "protective" role compared to halothane.

Rhabdomyolysis, oedema and arterial hypertension: different syndromes related to topical use of 9-alpha-fluoroprednisolone.

Over a one year period we detected five cases of iatrogenic mineralocorticoidism secondary to topical application of creams containing 9-alpha-fluoro-prednisolone. Although the same product was involved in all cases, the clinical features differed and included two cases of myopathy and hypokalemic rhabdomyolysis, one of oedema and two of arterial hypertension. Discontinuation of treatment and administration of potassium supplements produced a rapid recovery and all patients remain well six months later.