Rhabdomyolysis: A syndrome to be considered | Medicina Clínica (English Edition)

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CK: creatine kinase; U/L: units/litre; RML: rhabdomyolysis." ] ] ] "textoCompleto" => "IntroductionRhabdomyolysis (RML) is a syndrome characterised by the destruction of striated muscle (rhabdo-: striated, mio-: muscle, -lysis: destruction), which triggers the consequent release of intracellular elements such as electrolytes, myoglobin, creatine kinase (CK) and aldolase<a class="elsevierStyleCrossRef" href="#bib0005">1</a>. The first case of RML was reported in Germany in 1881, but it was Bywaters and Beall who described the syndrome in detail, with five cases reported in 1941 after the Battle of London during the Second World War<a class="elsevierStyleCrossRefs" href="#bib0010">2,3</a>. After two episodes of crushing, the patients had swelling of the limbs, shock and renal failure, leading to death. Tubular necrosis was observed in the autopsies.PathophysiologyRegardless of the aetiology of RML, the final phase is characterised by an increase in free ionised calcium in the cytoplasm due to adenosine triphosphate (ATP) depletion or by direct injury and plasma membrane rupture due to protease activation, increased muscle contractility, mitochondrial dysfunction and free radical production leading to muscle necrosis<a class="elsevierStyleCrossRefs" href="#bib0020">4,5</a>. This induces the release of different intracellular proteins and electrolytes, leading to hyperkalaemia, hyperphosphatemia, hyperuricaemia, metabolic acidosis and hypermagnesemia, especially in the presence of renal failure<a class="elsevierStyleCrossRef" href="#bib0030">6</a>.Myoglobin is an oxygen-carrying haemoprotein, whose muscle concentration is approximately 1–2% of dry weight, which appears in the circulation within a few hours after muscle damage, has a short half-life (1−3 h) and is filtered by the renal glomeruli and reabsorbed by the proximal tubules<a class="elsevierStyleCrossRef" href="#bib0035">7</a>. The presence of myoglobin in urine (myoglobinuria), common during LMN, is evident when urine levels are greater than 100 mg/dL<a class="elsevierStyleCrossRef" href="#bib0040">8</a>.CK is the most widely used intracellular and mitochondrial enzyme for diagnosing and monitoring muscle injuries. CK levels have a large inter-subject variability, with values below 100–175 U/L considered within the normal range in most studies, and values above five times the upper limit of normal being categorised as RML<a class="elsevierStyleCrossRef" href="#bib0045">9</a>. It has three different isoenzymes (MM, MB and BB), which in turn show two subunits, brain (B) and muscle (M), with the MM and MB isoenzymes being the most common in striated muscle<a class="elsevierStyleCrossRef" href="#bib0050">10</a>. In a context of muscle damage, its maximum peak occurs 13−24 h after the myoglobin peak, its half-life is approximately 36−48 h and levels decrease by 40–50% each day in situations of normal kidney function<a class="elsevierStyleCrossRef" href="#bib0035">7</a>. Especially noteworthy is the asymptomatic CK elevation, called hyperCKaemia, usually detected incidentally after a routine blood test, which tends to be normal on complementary muscle tests, and macroCK, consisting of CK and immunoglobulin complexes, which accounts for approximately 4% of asymptomatic CK elevations<a class="elsevierStyleCrossRefs" href="#bib0055">11,12</a>.Aldolase is a glycolytic enzyme present in many human tissues such as skeletal muscle, liver and brain. Although elevated after muscle injury, its usefulness has been restricted to patients with muscle pathology and normal CK values<a class="elsevierStyleCrossRef" href="#bib0065">13</a>.Lactate dehydrogenase (LDH) and aspartate aminotransferase (AST or GOT) are two enzymes that, in addition to being elevated during muscle damage for 6–10 days, have been described in a multitude of diseases and therefore are not taken into account<a class="elsevierStyleCrossRefs" href="#bib0070">14,15</a>.AetiologyThe aetiological spectrum of RML is broad, sometimes going unnoticed. While Zimmerman et al. used a classification based on its mechanism of injury (hypoxic, physical, chemical and biological), most authors classify this entity according to the causal agent<a class="elsevierStyleCrossRef" href="#bib0080">16</a>. Studies show that the most frequent aetiologies are trauma, immobilisation, sepsis, medication, recreational drugs and alcohol, while in children they are viral infections and exercise, in addition to those already mentioned<a class="elsevierStyleCrossRefs" href="#bib0085">17–20</a>.TraumaTrauma and crush injuries following natural disasters, accidents and multiple-casualty incidents are common causes of RML. Acute muscle compression, muscle ischaemia and prolonged immobilisation are the most commonly related mechanisms<a class="elsevierStyleCrossRefs" href="#bib0010">2,21</a>. RML occurs in up to 85% of patients with traumatic injuries, and these are the most commonly described causes of RML, with a prevalence of 30–40%<a class="elsevierStyleCrossRefs" href="#bib0085">17,19,20,22</a>. Renal dysfunction occurs in 24% of cases, while mortality is 10%<a class="elsevierStyleCrossRefs" href="#bib0095">19,23</a>. Factors associated with worse prognosis are advanced age, hypertension, diabetes mellitus, high Injury Severity Score, shock, coma and sepsis<a class="elsevierStyleCrossRefs" href="#bib0115">23,24</a>.Physical exercisePerforming intense physical exercise is an underdiagnosed cause of RML. It usually occurs in untrained individuals, those doing new or more intense than usual exercise<a class="elsevierStyleCrossRef" href="#bib0125">25</a>. Related risk factors are poor previous training, high room temperature, low fluid intake, poor diet and the coexistence of another cause of RML (statin treatment, illicit drugs, myopathies)<a class="elsevierStyleCrossRef" href="#bib0125">25</a>. Despite CK elevations above 30,000 U/L, exercise RML has a good response to fluid therapy, with a low prevalence of renal dysfunction. Creatine supplementation has been associated with an increased risk of renal dysfunction in exercise-induced RML<a class="elsevierStyleCrossRef" href="#bib0130">26</a>.Electrical injuryAlthough its prevalence is unknown, cases of RML secondary to high-voltage electrical injuries caused by lightning have been described<a class="elsevierStyleCrossRefs" href="#bib0135">27,28</a>. There are no conclusive data associating significant elevation of CK and the use of electric guns (TASER®)<a class="elsevierStyleCrossRef" href="#bib0145">29</a>.Surgery and prolonged immobilizationRML is a complication to be taken into account in surgical interventions and can occur in a multitude of procedures, but its prevalence is difficult to specify and may be underestimated in studies. Vascular surgery is the most common surgical cause (5–8%), followed by cardiac (6%) and abdominal and thoracic surgery, with high mortality in all of them<a class="elsevierStyleCrossRefs" href="#bib0095">19,20</a>. Factors related to this association are immobilisation time (more prevalent in those of more than six hours), male gender, body mass index and comorbidities such as hypertension and diabetes<a class="elsevierStyleCrossRef" href="#bib0030">6</a>. The positions most commonly associated with RML in prolonged immobilisation are lateral decubitus, lithotomy, seated, foetal and prone<a class="elsevierStyleCrossRef" href="#bib0150">30</a>.SeizuresSeizures are a likely cause of RML, with a frequency of 5–7%, due to muscle stress following attacks, with low mortality<a class="elsevierStyleCrossRefs" href="#bib0085">17,20</a>. In addition, cases have been reported secondary to antiepileptic medication in the days following recovery of CK values after a critical event, e.g., levetiracetam, valproic acid, phenytoin and gabapentin, which is an extremely rare side effect with the use of these drugs<a class="elsevierStyleCrossRef" href="#bib0155">31</a>.HyperthermiaNeuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH) present with altered mental status, rigidity, fever and dysautonomia, most often with elevated CK secondary to intense muscle contraction (depending on clinical presentation and progression time) and, to a lesser extent, myoglobinuria and ARF<a class="elsevierStyleCrossRef" href="#bib0160">32</a>. NMS is a clinical syndrome associated with the use of antipsychotic (neuroleptic) and antiemetic agents, while MH is a genetic, mainly autosomal dominant disorder related to anaesthetic agents and succinylcholine. During episodes, CK levels are higher than 1000 U/L, returning to normal after symptom resolution<a class="elsevierStyleCrossRef" href="#bib0165">33</a>. Likewise, elevations of CK have been described prior to an episode of RML in patients with NMS and in relatives of patients with MH<a class="elsevierStyleCrossRefs" href="#bib0170">34,35</a>. According to the literature, NMS is part of 0.5–8% of the causes of RML, with an unfavourable progression rate of more than one third, while MH is a less common cause of RML<a class="elsevierStyleCrossRefs" href="#bib0085">17,20</a>. RML can also be a complication of heat stroke<a class="elsevierStyleCrossRef" href="#bib0030">6</a>.Drug or alcohol abuseIllicit drugs are a common cause of RML, with a frequency of around 35%, with heroin, cocaine, lysergic acid diethylamide (LSD) and amphetamines being the most commonly described <a class="elsevierStyleCrossRefs" href="#bib0085">17,22</a>. It is estimated that 24% of cocaine users have elevated CK secondary to direct muscle toxicity, vasoconstriction and muscle ischaemia<a class="elsevierStyleCrossRef" href="#bib0180">36</a>. RML associated with heroin use may be related to heroin adulteration by different substances and immobility after use<a class="elsevierStyleCrossRef" href="#bib0180">36</a>. Amphetamines cause muscle damage through various mechanisms, including cellular hypermetabolism and decreased muscle perfusion<a class="elsevierStyleCrossRef" href="#bib0185">37</a>. Like opioids, alcohol can cause RML through direct myotoxicity and prolonged immobilisation, as well as absence of alcohol consumption leading to episodes of delirium tremens<a class="elsevierStyleCrossRefs" href="#bib0085">17,36</a>.Pharmaceutical drugsAny drug that directly or indirectly alters the production or use of ATP by skeletal muscle or increases energy requirements beyond the rate of ATP production, can cause RML<a class="elsevierStyleCrossRef" href="#bib0110">22</a>. This etiological group has a mortality of 10.8%<a class="elsevierStyleCrossRef" href="#bib0190">38</a>. Cases of RML secondary to the use of multiple drugs have been reported, including various antibiotics, antivirals and antiparasitic drugs (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), especially in combination with statins, the most common pharmacological group<a class="elsevierStyleCrossRefs" href="#bib0190">38–40</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Statins account for less than 5% of cases of RML, with simvastatin being the most common, twice as frequent as atorvastatin, with an incidence rate per year of treatment of 0.0042%<a class="elsevierStyleCrossRefs" href="#bib0095">19,20,38,41</a>,<a class="elsevierStyleCrossRef" href="#bib0210">42</a>. This incidence increases in the lipid-lowering associations of statins and fibrate<a class="elsevierStyleCrossRef" href="#bib0205">41</a>. The recall of cerivastatin in 2001 due to its association with RML and mortality should be emphasised. Although hyperCKaemia is the most commonly associated condition, RML can be observed with a variety of muscle manifestations. The mechanisms by which statins can induce muscle injury are not well established. Multiple triggers have been described, such as its influence on membrane excitability, mitochondrial function mediated by reduced ubiquinone (coenzyme Q10) levels, altered calcium homeostasis and induction of skeletal muscle apoptosis<a class="elsevierStyleCrossRef" href="#bib0215">43</a>. Risk factors associated with statin use and the presence of RML are age over 80, frailty, renal or hepatic dysfunction, hypothyroidism, alcohol consumption, excessive exercise and treatment associated with agents that affect the cytochrome P450<a class="elsevierStyleCrossRef" href="#bib0210">42</a> system. This pharmacological group has been described as a trigger for polymyositis associated with anti-HMGCR antibodies<a class="elsevierStyleCrossRef" href="#bib0220">44</a>.InfectionsInfectious aetiology accounts for 10–16% of RML cases, with a poor prognosis of approximately 40%<a class="elsevierStyleCrossRefs" href="#bib0085">17,19</a>. Proposed mechanisms are tissue hypoxia, direct muscle invasion, and mechanisms involving endotoxins, sometimes aggravated by the use of treatment<a class="elsevierStyleCrossRef" href="#bib0030">6</a>. Multiple bacteria, viruses, fungi, and protozoa can cause RML, with influenza A, B, and HIV being the most common<a class="elsevierStyleCrossRef" href="#bib0030">6</a>. Cases secondary to SARS-CoV2 infection have recently been described<a class="elsevierStyleCrossRef" href="#bib0225">45</a>. Among the most common bacteria are, Legionella sp., Streptococcus sp., and enterobacteria, especially in cases of sepsis<a class="elsevierStyleCrossRefs" href="#bib0030">6,19</a>.Hereditary disordersHereditary disorders of carbohydrate, lipid, and mitochondrial metabolism have been described as causes of RML in subjects with exercise intolerance and elevated CK, especially in patients with inadequate intake. Carnitine palmitoyltransferase deficiency (an autosomal recessive disorder) is the most closely related hereditary disease, followed by McArdle syndrome (myophosphorylase deficiency) and myoadenylate deaminase deficiency, or MADA<a class="elsevierStyleCrossRefs" href="#bib0005">1,6,22</a>. Although the definitive diagnosis is made by genetic study, after the initial suspicion it could be useful to perform a complete laboratory test (including free and total carnitine, lactate, pyruvate and ketones), as well as a stress test or lactate and ammonium curve. This is based on the placement of a sphygmomanometer on the dominant arm, above the elbow flexure, compressing the forearm muscles by inflating the cuff to a certain pressure, then the patient performs muscular exercise, squeezing and releasing the cuff and performing plasma lactate and ammonium tests at 1, 2, 5 and 10 min after finishing the exercise. In normal subjects, a gradual elevation of lactate and ammonium is observed. In patients with carbohydrate metabolism defects (McArdle), normal ammonium elevation without lactate elevation is observed (positive ammonium curve and flat lactate curve), while in those with MADA deficiency the results are reversed, and in those with lipid metabolism disorders no abnormalities would be observed<a class="elsevierStyleCrossRef" href="#bib0230">46</a>. The presence of ketonuria may raise suspicion of metabolic myopathy. Muscle biopsy is often necessary to confirm the diagnosis. Although no targeted treatment is available, it is advisable to adapt physical exercise according to the altered metabolic pathway and dietary treatment.Other causesCases of RML have been described in patients with endocrine disorders such as hypo- and hyperthyroidism, hyperaldosteronism, diabetes mellitus, and diabetic ketoacidosis<a class="elsevierStyleCrossRefs" href="#bib0030">6,18,20,22</a>.Clinical manifestationsThe initial symptoms of RML are extremely variable and generally mirror the primary causative disease process. The characteristic triad consists of muscle pain, usually moderate, weakness and dark urine, which is absent in up to 50% of cases<a class="elsevierStyleCrossRefs" href="#bib0235">47,48</a>. The most commonly affected muscle groups are the proximal muscles of the lower limbs and the lumbar region, often resembling deep vein thrombosis and renal colic<a class="elsevierStyleCrossRef" href="#bib0110">22</a>. The affected muscles may be enlarged and skin changes indicating pressure necrosis may be observed. A change in urine colour corresponding to the amount of myoglobinuria is sometimes the initial symptom. General manifestations include malaise, fever, tachycardia, nausea and vomiting<a class="elsevierStyleCrossRef" href="#bib0020">4</a>.ComplicationsAcute complications are related to ionic disturbances following muscle destruction. Hyperkalaemia, which occurs acutely, can lead to cardiac arrhythmias. Even an acute necrosis of only 100 g of muscle mass could increase potassium by 1 mEq/L<a class="elsevierStyleCrossRef" href="#bib0020">4</a>. Serum calcium levels are initially low, especially in patients with kidney disease, but should return to normal during the recovery phase<a class="elsevierStyleCrossRef" href="#bib0245">49</a>. Protease release can cause liver dysfunction in 25% of patients with RML<a class="elsevierStyleCrossRef" href="#bib0250">50</a>.The release of prothrombotic substances during muscle destruction activates the coagulation cascade, which can trigger disseminated intravascular coagulopathy, which is a late complication (12−72 h)<a class="elsevierStyleCrossRef" href="#bib0255">51</a>.Compartment syndrome is a serious complication often associated with muscle injuries accompanied by fracture, especially in the tibia and forearm<a class="elsevierStyleCrossRef" href="#bib0260">52</a>. The massive entry of calcium and sodium promotes the accumulation of extracellular fluid inside the cells, causing local oedema and an increase in intramuscular pressure, preventing blood circulation in the area and thus intensifying the edema<a class="elsevierStyleCrossRef" href="#bib0255">51</a>. The characteristic symptom is greater than expected muscle pain, accompanied by pallor, absence of pulse and, in severe cases, limb ischaemia.Acute renal failureAcute renal failure (ARF) is the most important complication of RML. Its frequency is highly variable, estimating figures of 10–50% and a mortality also variable of 3–32% that increases to more than 50% in critical patients<a class="elsevierStyleCrossRefs" href="#bib0085">17,53–55</a>. Illicit drug intoxication and alcohol abuse are the aetiologies of RML most closely related to ARF<a class="elsevierStyleCrossRef" href="#bib0085">17</a>. The mechanism of injury leading to ARF is determined by three processes: vasoconstriction, ischaemia and direct tubular injury. During muscle destruction, intracellular fluid is sequestered into the extracellular space, leading to hypovolaemia and activating the renin-angiotensin-aldosterone system, which in turn increases the production of vasoconstrictor molecules and inhibits the production of prostaglandins, thus decreasing renal flow<a class="elsevierStyleCrossRef" href="#bib0090">18</a>. On the other hand, myoglobin, together with volume depletion and renal vasoconstriction, exerts a cytotoxic effect on the nephron, both directly by interacting with the Tamm-Horsfall protein, as well as through the free iron released after its degradation<a class="elsevierStyleCrossRefs" href="#bib0005">1,21,56</a>. The presence of acidosis enhances myoglobin nephrotoxicity through cast formation and tubular obstruction, particularly in the distal convoluted tubules<a class="elsevierStyleCrossRef" href="#bib0090">18</a>.Although there is no standardised cut-off value for myoglobin that causes renal injury, high myoglobin levels (15−20 mg/L) have been reported to be associated with creatinine levels, development of ARF and the need for haemodialysis<a class="elsevierStyleCrossRef" href="#bib0285">57</a>. No association was found between urinary myoglobin values and ARF<a class="elsevierStyleCrossRef" href="#bib0290">58</a>. There is no defined threshold value for CK related to the risk of ARF, but its proportion increases at levels above 15,000 U/L and is uncertain at lower levels<a class="elsevierStyleCrossRefs" href="#bib0095">19,53,54</a>. A recent review links LDH levels to worsening kidney function<a class="elsevierStyleCrossRef" href="#bib0295">59</a>.McMahon et al. proposed an ARF index in RML (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>), which includes the variables age, sex, aetiology and initial creatinine, CK, phosphate, bicarbonate and calcium values<a class="elsevierStyleCrossRef" href="#bib0100">20</a>. A McMahon score below five indicates a 2−3% risk of ARF or death, while a score above 10 raises the risk to 52–61.2%<a class="elsevierStyleCrossRef" href="#bib0100">20</a>. Figures greater than six reflect kidney damage and, according to the authors, renal protection therapies would be indicated<a class="elsevierStyleCrossRef" href="#bib0100">20</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Etiological diagnosisDiagnostic evaluation of RML should be performed in patients with acute muscle symptoms, in those with dark urine in the presence of myoglobinuria, or in those with exercise intolerance (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The confirmation of RML is subject to the elevation of CK, whose serialization and monitoring is necessary to know the temporal status of RML and prognosis<a class="elsevierStyleCrossRefs" href="#bib0095">19,53,54</a>. Likewise, CK levels stratify the severity of RML. Values below 5000 U/L (mild RML) have a low probability of developing renal involvement, while those between 5,000–15,000 U/L (moderate) have a high risk of renal failure and those > 15,000 U/L (severe) have a high risk of dialysis<a class="elsevierStyleCrossRef" href="#bib0105">21</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The clinical history and physical examination are the fundamental basis for making an aetiological diagnosis of elevated CK, including personal history, trauma, immobilisation, toxic habits, treatments and symptoms that point to an infectious cause. Along with CK values, myoglobin values and the presence of myoglobinuria will be requested, in addition to the required parameters based on the suspected aetiology such as blood gases, complete blood count, coagulation and toxicological study.Muscle biopsy and electromyogram are not necessary, although they can be used to confirm the diagnosis of RML and could be performed if metabolic or inflammatory myopathy is suspected<a class="elsevierStyleCrossRef" href="#bib0030">6</a>. A muscle biopsy should wait several weeks or months after the clinical event, as the results of a biopsy will not be informative in the early stages<a class="elsevierStyleCrossRef" href="#bib0105">21</a>. When exercise intolerance or metabolic myopathy is suspected, the exercise test or lactate-ammonium curve may be performed as a non-invasive diagnostic test<a class="elsevierStyleCrossRef" href="#bib0230">46</a>.TreatmentWhen RML is suspected, regardless of the cause, the most important goal is to preserve renal function (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). This objective is even more important in those patients with moderate-severe RML, or what is the same, CK values greater than 15,000 U/L or a McMahon score above 10<a class="elsevierStyleCrossRefs" href="#bib0100">20,21</a>. Renal prevention should be initiated as early as possible by administering fluid therapy to maintain or improve renal perfusion, minimise ischaemic injury and to increase urine flow rate, which will limit the formation of intratubular casts by diluting the heme pigment concentration within the tubular fluid, remove partially obstructing intratubular casts and increase urinary excretion of potassium<a class="elsevierStyleCrossRef" href="#bib0090">18</a>. It has been shown that haste in volume replacement is directly proportional to progression to ARF<a class="elsevierStyleCrossRefs" href="#bib0105">21,22</a>. Although the need for volume replacement is established, the composition of the fluid used for volume replacement remains controversial, with no clinical trials or clear recommendations available<a class="elsevierStyleCrossRef" href="#bib0300">60</a>. Studies with Ringer’s lactate, glucose saline, isotonic saline and hypotonic saline have shown benefits, with no clear differences between them in terms of time to normal CK levels and favourable prognosis, with individualisation of each case being paramount<a class="elsevierStyleCrossRef" href="#bib0300">60</a>. Patients with RML may require considerable amounts of fluid therapy at an initial rate of up to 1.5 L/h and subsequently 300−500 mL/h<a class="elsevierStyleCrossRef" href="#bib0030">6</a>.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Bicarbonate administration is aimed at alkalinisation of the urine (pH > 6.5), in order to prevent myoglobin precipitation in the renal tubules and renal dysfunction. Its use is more recommended in those patients with moderate-severe RML without hypocalcaemia, with arterial pH below 7.5 and serum bicarbonate below 30 mEq/L<a class="elsevierStyleCrossRef" href="#bib0105">21</a>. Its usefulness is contradictory for some authors, no benefits being observed when it is administered jointly with saline compared to Ringer's lactate<a class="elsevierStyleCrossRefs" href="#bib0005">1,61</a>. The recommended dose is 44–50 mEq per 2 L of serum<a class="elsevierStyleCrossRef" href="#bib0300">60</a>. There is no consensus on the use of mannitol. Its use is recommended if fluid therapy alone does not produce a diuresis greater than 300 mL/h and contraindicated in anuric patients<a class="elsevierStyleCrossRef" href="#bib0090">18</a>. Plasma osmolarity and anion gap should be monitored during use and should be discontinued if it exceeds 55 mOsm/kg<a class="elsevierStyleCrossRef" href="#bib0005">1</a>. The administration of loop diuretics has not shown a clear improvement, in addition to being able to lower urinary pH<a class="elsevierStyleCrossRef" href="#bib0255">51</a>.An appropriate fluid management approach could start with intravenous saline solution at 1 L/h. Subsequently administer 500 mL of isotonic saline, alternating with 500 mL of 5% glucose, maintaining the infusion rate at 1 L/h and adding 50 mEq of bicarbonate per 2−3 L to maintain urinary pH > 6.5. Once diuresis has been established, if it is not greater than 300 mL/h, it would be appropriate to administer a 20% mannitol solution (1 g/kg) for 4 h. Treatment should be continued until the progressive decrease in CK levels and myoglobinuria is confirmed, with special attention to the risk of fluid overload<a class="elsevierStyleCrossRefs" href="#bib0105">21,60</a>. It is recommended to control ions (potassium and calcium), plasma pH and electrocardiographic monitoring in the face of these abnormalities<a class="elsevierStyleCrossRef" href="#bib0005">1</a>. The use of renal replacement therapy is limited to life-threatening electrolyte disturbances (hypercalcemia, hyperkalaemia) that do not respond to initial treatment, overhydration, or in anuric renal failure<a class="elsevierStyleCrossRefs" href="#bib0030">6,18,62</a>.ConclusionsRML is a clinical entity to be considered due to its varied aetiology and potential complications, whose aetiological diagnosis is based on a good history-taking and physical examination. Treatment, based on volume replacement, should be started early to maintain or improve renal function and avoid the most common and life-threatening complication, acute renal failure. The total volume required must be individualized and adjusted according to diuresis. Although there is no consensus on the composition of the fluid to be used, its use is even more important in patients with CK values above 15,000 U/L.Conflict of interestsThe author declares that he has no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1695807" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1502053" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1695806" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1502054" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Pathophysiology" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Aetiology" "secciones" => array:11 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Trauma" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Physical exercise" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Electrical injury" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Surgery and prolonged immobilization" ] 4 => array:2 [ "identificador" => "sec0040" "titulo" => "Seizures" ] 5 => array:2 [ "identificador" => "sec0045" "titulo" => "Hyperthermia" ] 6 => array:2 [ "identificador" => "sec0050" "titulo" => "Drug or alcohol abuse" ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Pharmaceutical drugs" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Infections" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Hereditary disorders" ] 10 => array:2 [ "identificador" => "sec0070" "titulo" => "Other causes" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Clinical manifestations" ] 8 => array:3 [ "identificador" => "sec0080" "titulo" => "Complications" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0085" "titulo" => "Acute renal failure" ] ] ] 9 => array:2 [ "identificador" => "sec0090" "titulo" => "Etiological diagnosis" ] 10 => array:2 [ "identificador" => "sec0095" "titulo" => "Treatment" ] 11 => array:2 [ "identificador" => "sec0100" "titulo" => "Conclusions" ] 12 => array:2 [ "identificador" => "sec0105" "titulo" => "Conflict of interests" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-07-29" "fechaAceptado" => "2021-09-24" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1502053" "palabras" => array:4 [ 0 => "Rhabdomyolysis" 1 => "Creatine kinase" 2 => "Myoglobin" 3 => "Acute kidney injury" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1502054" "palabras" => array:4 [ 0 => "Rabdomiólisis" 1 => "Creatincinasa" 2 => "Mioglobina" 3 => "Fracaso renal agudo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Rhabdomyolysis is characterized by the release of intracellular elements after the destruction of skeletal muscle. Is characterized by the presence of muscle pain, weakness, and dark urine, associated with elevated creatine kinase (CK). The causes related to this syndrome are varied, being traumatic etiology, immobilization, sepsis, drugs and alcohol the most frequent. CK values are used for diagnosis and prognosis, being renal dysfunction the most serious complication. Treatment is based on early and intensive fluid therapy to avoid kidney complications." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La rabdomiólisis es una entidad clínica caracterizada por la liberación de elementos intracelulares tras la destrucción del músculo esquelético. La tríada clásica se caracteriza por la presencia de dolor muscular, debilidad y orina oscura, asociada a elevación de la creatincinasa (CK). Las causas relacionadas con este síndrome son variadas, siendo la etiología traumática, inmovilización, sepsis, drogas, fármacos y alcohol, las más frecuentes. Los valores de CK son utilizados como diagnóstico y pronóstico, siendo la disfunción renal la complicación más grave. El tratamiento se basa en la fluidoterapia intensiva y precoz para evitar complicaciones renales." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Baeza-Trinidad R. Rabdomiólisis: un síndrome a tener en cuenta. Med Clin (Barc). 2022;158:277–283." ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2347 "Ancho" => 2500 "Tamanyo" => 280546 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Evaluation for suspected rhabdomyolysis. CK: creatine kinase; U/L: units/litre; RML: rhabdomyolysis." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pharmacological group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drugs \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antipsychotics/antidepressants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amitriptyline, fluoxetine, haloperidol, lithium, chlorpromazine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypnotics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Benzodiazepines, barbiturates \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antihistamines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diphenylamine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anaesthetics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Succinylcholine, propofol \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lipid-lowering agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Statins \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ezetimibe \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fibrates \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antibiotics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Polymyxins \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oxazolidinones \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lipopeptides \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antitubercular agents \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protein synthesis inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Quinolones \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Macrolides \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Colistin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Co-trimoxazole \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antivirals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protease inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Integrase inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nucleoside reverse transcriptase inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oseltamivir \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nucleoside analogues \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antiparasitics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antimalarials \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amphotericin B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antiprotozoals \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glucocorticoids, colchicine, quinidine, salicylates, thiazides… \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2882766.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Drugs related to rhabdomyolysis." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "A score <5 indicates a low risk of renal failure or death and >6 indicates the need for renal protective therapy.CK: creatine kinase; mg/dL: milligrams/decilitre; U/L: units/litre; mEq/L: milliequivalents/litre." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Score \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50−70 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70−80 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>80 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baseline creatinine</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.4−2.2 mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">> 2.2 mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baseline calcium <7.5 mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Initial CK >40,000 U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aetiology other than seizures, syncope, exercise, statins, or myositis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Initial phosphate</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4−5.4 mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">> 5.4 mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Initial bicarbonate <19 mEq/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2882767.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Variables of the acute renal failure score in rhabdomyolysis<a class="elsevierStyleCrossRef" href="#bib0100">20</a>." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "RML: rhabdomyolysis; mL: millilitres; mEq: milliequivalents; mOsm: milliosmoles; RRT: renal replacement therapy." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluid therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Premature and intense volume replacement, especially in moderate-severe RML \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Administration of fluid therapy at a rate of 1 L/h (for example, in the initial phases saline solution and later combination with dextrose solution) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Depending on diuresis and progression, reduce to 300−500 mL/h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Consider the administration of loop diuretics in overhydration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bicarbonate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 mEq/L in every 2−3 L of fluid therapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommended especially in moderate-severe rhabdomyolysis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The goal is to achieve urinary pH values > 6.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Limit its use if hypocalcaemia, arterial pH < 7.5 or serum bicarbonate <30 mEq/L \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mannitol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">There is no consensus on its use. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommended use if an initial diuresis of 300 mL/h is not achieved. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Administration of 1 g/kg for 4 h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Contraindicated in anuric patients and discontinue if anion gap >55 mOsm/kg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RRT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Use in electrolyte abnormalities that do not respond to conservative management, overhydration or anuria \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2882768.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Treatment of rhabdomyolysis." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:62 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rhabdomyolysis and acute kidney injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "X. 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Rhabdomyolysis: A syndrome to be considered

Rabdomiólisis: un síndrome a tener en cuenta

Ramón Baeza-Trinidad

Servicio de Medicina Interna, Hospital San Pedro, Logroño, Spain

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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evaluation for suspected rhabdomyolysis&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CK&#58; creatine kinase&#59; U&#47;L&#58; units&#47;litre&#59; RML&#58; rhabdomyolysis&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Rhabdomyolysis &#40;RML&#41; is a syndrome characterised by the destruction of striated muscle &#40;<span class="elsevierStyleItalic">rhabdo</span>-&#58; striated&#44; <span class="elsevierStyleItalic">mio</span>-&#58; muscle&#44; -<span class="elsevierStyleItalic">lysis</span>&#58; destruction&#41;&#44; which triggers the consequent release of intracellular elements such as electrolytes&#44; myoglobin&#44; creatine kinase &#40;CK&#41; and aldolase<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; The first case of RML was reported in Germany in 1881&#44; but it was Bywaters and Beall who described the syndrome in detail&#44; with five cases reported in 1941 after the Battle of London during the Second World War<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a>&#46; After two episodes of crushing&#44; the patients had swelling of the limbs&#44; <span class="elsevierStyleItalic">shock</span> and renal failure&#44; leading to death&#46; Tubular necrosis was observed in the autopsies&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Pathophysiology</span><p id="par0010" class="elsevierStylePara elsevierViewall">Regardless of the aetiology of RML&#44; the final phase is characterised by an increase in free ionised calcium in the cytoplasm due to adenosine triphosphate &#40;ATP&#41; depletion or by direct injury and plasma membrane rupture due to protease activation&#44; increased muscle contractility&#44; mitochondrial dysfunction and free radical production leading to muscle necrosis<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a>&#46; This induces the release of different intracellular proteins and electrolytes&#44; leading to hyperkalaemia&#44; hyperphosphatemia&#44; hyperuricaemia&#44; metabolic acidosis and hypermagnesemia&#44; especially in the presence of renal failure<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Myoglobin is an oxygen-carrying haemoprotein&#44; whose muscle concentration is approximately 1&#8211;2&#37; of dry weight&#44; which appears in the circulation within a few hours after muscle damage&#44; has a short half-life &#40;1&#8722;3&#8239;h&#41; and is filtered by the renal glomeruli and reabsorbed by the proximal tubules<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46; The presence of myoglobin in urine &#40;myoglobinuria&#41;&#44; common during LMN&#44; is evident when urine levels are greater than 100&#8239;mg&#47;dL<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">CK is the most widely used intracellular and mitochondrial enzyme for diagnosing and monitoring muscle injuries&#46; CK levels have a large inter-subject variability&#44; with values below 100&#8211;175 U&#47;L considered within the normal range in most studies&#44; and values above five times the upper limit of normal being categorised as RML<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; It has three different isoenzymes &#40;MM&#44; MB and BB&#41;&#44; which in turn show two subunits&#44; brain &#40;B&#41; and muscle &#40;M&#41;&#44; with the MM and MB isoenzymes being the most common in striated muscle<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46; In a context of muscle damage&#44; its maximum peak occurs 13&#8722;24&#8239;h after the myoglobin peak&#44; its half-life is approximately 36&#8722;48&#8239;h and levels decrease by 40&#8211;50&#37; each day in situations of normal kidney function<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46; Especially noteworthy is the asymptomatic CK elevation&#44; called hyperCKaemia&#44; usually detected incidentally after a routine blood test&#44; which tends to be normal on complementary muscle tests&#44; and macroCK&#44; consisting of CK and immunoglobulin complexes&#44; which accounts for approximately 4&#37; of asymptomatic CK elevations<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Aldolase is a glycolytic enzyme present in many human tissues such as skeletal muscle&#44; liver and brain&#46; Although elevated after muscle injury&#44; its usefulness has been restricted to patients with muscle pathology and normal CK values<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Lactate dehydrogenase &#40;LDH&#41; and aspartate aminotransferase &#40;AST or GOT&#41; are two enzymes that&#44; in addition to being elevated during muscle damage for 6&#8211;10 days&#44; have been described in a multitude of diseases and therefore are not taken into account<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a>&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Aetiology</span><p id="par0035" class="elsevierStylePara elsevierViewall">The aetiological spectrum of RML is broad&#44; sometimes going unnoticed&#46; While Zimmerman et al&#46; used a classification based on its mechanism of injury &#40;hypoxic&#44; physical&#44; chemical and biological&#41;&#44; most authors classify this entity according to the causal agent<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; Studies show that the most frequent aetiologies are trauma&#44; immobilisation&#44; sepsis&#44; medication&#44; recreational drugs and alcohol&#44; while in children they are viral infections and exercise&#44; in addition to those already mentioned<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#8211;20</span></a>&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Trauma</span><p id="par0040" class="elsevierStylePara elsevierViewall">Trauma and crush injuries following natural disasters&#44; accidents and multiple-casualty incidents are common causes of RML&#46; Acute muscle compression&#44; muscle ischaemia and prolonged immobilisation are the most commonly related mechanisms<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;21</span></a>&#46; RML occurs in up to 85&#37; of patients with traumatic injuries&#44; and these are the most commonly described causes of RML&#44; with a prevalence of 30&#8211;40&#37;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;19&#44;20&#44;22</span></a>&#46; Renal dysfunction occurs in 24&#37; of cases&#44; while mortality is 10&#37;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;23</span></a>&#46; Factors associated with worse prognosis are advanced age&#44; hypertension&#44; diabetes mellitus&#44; high <span class="elsevierStyleItalic">Injury Severity Score</span>&#44; <span class="elsevierStyleItalic">shock</span>&#44; coma and sepsis<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;24</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Physical exercise</span><p id="par0045" class="elsevierStylePara elsevierViewall">Performing intense physical exercise is an underdiagnosed cause of RML&#46; It usually occurs in untrained individuals&#44; those doing new or more intense than usual exercise<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46; Related risk factors are poor previous training&#44; high room temperature&#44; low fluid intake&#44; poor diet and the coexistence of another cause of RML &#40;statin treatment&#44; illicit drugs&#44; myopathies&#41;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46; Despite CK elevations above 30&#44;000&#8239;U&#47;L&#44; exercise RML has a good response to fluid therapy&#44; with a low prevalence of renal dysfunction&#46; Creatine supplementation has been associated with an increased risk of renal dysfunction in exercise-induced RML<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Electrical injury</span><p id="par0050" class="elsevierStylePara elsevierViewall">Although its prevalence is unknown&#44; cases of RML secondary to high-voltage electrical injuries caused by lightning have been described<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a>&#46; There are no conclusive data associating significant elevation of CK and the use of electric guns &#40;TASER&#174;&#41;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Surgery and prolonged immobilization</span><p id="par0055" class="elsevierStylePara elsevierViewall">RML is a complication to be taken into account in surgical interventions and can occur in a multitude of procedures&#44; but its prevalence is difficult to specify and may be underestimated in studies&#46; Vascular surgery is the most common surgical cause &#40;5&#8211;8&#37;&#41;&#44; followed by cardiac &#40;6&#37;&#41; and abdominal and thoracic surgery&#44; with high mortality in all of them<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a>&#46; Factors related to this association are immobilisation time &#40;more prevalent in those of more than six hours&#41;&#44; male gender&#44; body mass index and comorbidities such as hypertension and diabetes<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; The positions most commonly associated with RML in prolonged immobilisation are lateral decubitus&#44; lithotomy&#44; seated&#44; foetal and prone<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Seizures</span><p id="par0060" class="elsevierStylePara elsevierViewall">Seizures are a likely cause of RML&#44; with a frequency of 5&#8211;7&#37;&#44; due to muscle stress following attacks&#44; with low mortality<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;20</span></a>&#46; In addition&#44; cases have been reported secondary to antiepileptic medication in the days following recovery of CK values after a critical event&#44; e&#46;g&#46;&#44; levetiracetam&#44; valproic acid&#44; phenytoin and gabapentin&#44; which is an extremely rare side effect with the use of these drugs<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Hyperthermia</span><p id="par0065" class="elsevierStylePara elsevierViewall">Neuroleptic malignant syndrome &#40;NMS&#41; and malignant hyperthermia &#40;MH&#41; present with altered mental status&#44; rigidity&#44; fever and dysautonomia&#44; most often with elevated CK secondary to intense muscle contraction &#40;depending on clinical presentation and progression time&#41; and&#44; to a lesser extent&#44; myoglobinuria and ARF<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#46; NMS is a clinical syndrome associated with the use of antipsychotic &#40;neuroleptic&#41; and antiemetic agents&#44; while MH is a genetic&#44; mainly autosomal dominant disorder related to anaesthetic agents and succinylcholine&#46; During episodes&#44; CK levels are higher than 1000&#8239;U&#47;L&#44; returning to normal after symptom resolution<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a>&#46; Likewise&#44; elevations of CK have been described prior to an episode of RML in patients with NMS and in relatives of patients with MH<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35</span></a>&#46; According to the literature&#44; NMS is part of 0&#46;5&#8211;8&#37; of the causes of RML&#44; with an unfavourable progression rate of more than one third&#44; while MH is a less common cause of RML<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;20</span></a>&#46; RML can also be a complication of heat stroke<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Drug or alcohol abuse</span><p id="par0070" class="elsevierStylePara elsevierViewall">Illicit drugs are a common cause of RML&#44; with a frequency of around 35&#37;&#44; with heroin&#44; cocaine&#44; lysergic acid diethylamide &#40;LSD&#41; and amphetamines being the most commonly described <a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;22</span></a>&#46; It is estimated that 24&#37; of cocaine users have elevated CK secondary to direct muscle toxicity&#44; vasoconstriction and muscle ischaemia<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&#46; RML associated with heroin use may be related to heroin adulteration by different substances and immobility after use<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&#46; Amphetamines cause muscle damage through various mechanisms&#44; including cellular hypermetabolism and decreased muscle perfusion<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&#46; Like opioids&#44; alcohol can cause RML through direct myotoxicity and prolonged immobilisation&#44; as well as absence of alcohol consumption leading to episodes of <span class="elsevierStyleItalic">delirium tremens</span><a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;36</span></a>&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Pharmaceutical drugs</span><p id="par0075" class="elsevierStylePara elsevierViewall">Any drug that directly or indirectly alters the production or use of ATP by skeletal muscle or increases energy requirements beyond the rate of ATP production&#44; can cause RML<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#46; This etiological group has a mortality of 10&#46;8&#37;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#46; Cases of RML secondary to the use of multiple drugs have been reported&#44; including various antibiotics&#44; antivirals and antiparasitic drugs &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; especially in combination with statins&#44; the most common pharmacological group<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38&#8211;40</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Statins account for less than 5&#37; of cases of RML&#44; with simvastatin being the most common&#44; twice as frequent as atorvastatin&#44; with an incidence rate per year of treatment of 0&#46;0042&#37;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20&#44;38&#44;41</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#46; This incidence increases in the lipid-lowering associations of statins and fibrate<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&#46; The recall of cerivastatin in 2001 due to its association with RML and mortality should be emphasised&#46; Although hyperCKaemia is the most commonly associated condition&#44; RML can be observed with a variety of muscle manifestations&#46; The mechanisms by which statins can induce muscle injury are not well established&#46; Multiple triggers have been described&#44; such as its influence on membrane excitability&#44; mitochondrial function mediated by reduced ubiquinone &#40;coenzyme Q10&#41; levels&#44; altered calcium homeostasis and induction of skeletal muscle apoptosis<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a>&#46; Risk factors associated with statin use and the presence of RML are age over 80&#44; frailty&#44; renal or hepatic dysfunction&#44; hypothyroidism&#44; alcohol consumption&#44; excessive exercise and treatment associated with agents that affect the cytochrome P450<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> system&#46; This pharmacological group has been described as a trigger for polymyositis associated with anti-HMGCR antibodies<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a>&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Infections</span><p id="par0085" class="elsevierStylePara elsevierViewall">Infectious aetiology accounts for 10&#8211;16&#37; of RML cases&#44; with a poor prognosis of approximately 40&#37;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;19</span></a>&#46; Proposed mechanisms are tissue hypoxia&#44; direct muscle invasion&#44; and mechanisms involving endotoxins&#44; sometimes aggravated by the use of treatment<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; Multiple bacteria&#44; viruses&#44; fungi&#44; and protozoa can cause RML&#44; with influenza A&#44; B&#44; and HIV being the most common<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; Cases secondary to SARS-CoV2 infection have recently been described<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a>&#46; Among the most common bacteria are&#44; <span class="elsevierStyleItalic">Legionella</span> sp&#46;&#44; <span class="elsevierStyleItalic">Streptococcus</span> sp&#46;&#44; and enterobacteria&#44; especially in cases of sepsis<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;19</span></a>&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Hereditary disorders</span><p id="par0090" class="elsevierStylePara elsevierViewall">Hereditary disorders of carbohydrate&#44; lipid&#44; and mitochondrial metabolism have been described as causes of RML in subjects with exercise intolerance and elevated CK&#44; especially in patients with inadequate intake&#46; Carnitine palmitoyltransferase deficiency &#40;an autosomal recessive disorder&#41; is the most closely related hereditary disease&#44; followed by McArdle syndrome &#40;myophosphorylase deficiency&#41; and myoadenylate deaminase deficiency&#44; or MADA<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;6&#44;22</span></a>&#46; Although the definitive diagnosis is made by genetic study&#44; after the initial suspicion it could be useful to perform a complete laboratory test &#40;including free and total carnitine&#44; lactate&#44; pyruvate and ketones&#41;&#44; as well as a stress test or lactate and ammonium curve&#46; This is based on the placement of a sphygmomanometer on the dominant arm&#44; above the elbow flexure&#44; compressing the forearm muscles by inflating the cuff to a certain pressure&#44; then the patient performs muscular exercise&#44; squeezing and releasing the cuff and performing plasma lactate and ammonium tests at 1&#44; 2&#44; 5 and 10&#8239;min after finishing the exercise&#46; In normal subjects&#44; a gradual elevation of lactate and ammonium is observed&#46; In patients with carbohydrate metabolism defects &#40;McArdle&#41;&#44; normal ammonium elevation without lactate elevation is observed &#40;positive ammonium curve and flat lactate curve&#41;&#44; while in those with MADA deficiency the results are reversed&#44; and in those with lipid metabolism disorders no abnormalities would be observed<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a>&#46; The presence of ketonuria may raise suspicion of metabolic myopathy&#46; Muscle biopsy is often necessary to confirm the diagnosis&#46; Although no targeted treatment is available&#44; it is advisable to adapt physical exercise according to the altered metabolic pathway and dietary treatment&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Other causes</span><p id="par0095" class="elsevierStylePara elsevierViewall">Cases of RML have been described in patients with endocrine disorders such as hypo- and hyperthyroidism&#44; hyperaldosteronism&#44; diabetes mellitus&#44; and diabetic ketoacidosis<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;18&#44;20&#44;22</span></a>&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Clinical manifestations</span><p id="par0100" class="elsevierStylePara elsevierViewall">The initial symptoms of RML are extremely variable and generally mirror the primary causative disease process&#46; The characteristic triad consists of muscle pain&#44; usually moderate&#44; weakness and dark urine&#44; which is absent in up to 50&#37; of cases<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;48</span></a>&#46; The most commonly affected muscle groups are the proximal muscles of the lower limbs and the lumbar region&#44; often resembling deep vein thrombosis and renal colic<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#46; The affected muscles may be enlarged and skin changes indicating pressure necrosis may be observed&#46; A change in urine colour corresponding to the amount of myoglobinuria is sometimes the initial symptom&#46; General manifestations include malaise&#44; fever&#44; tachycardia&#44; nausea and vomiting<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Complications</span><p id="par0105" class="elsevierStylePara elsevierViewall">Acute complications are related to ionic disturbances following muscle destruction&#46; Hyperkalaemia&#44; which occurs acutely&#44; can lead to cardiac arrhythmias&#46; Even an acute necrosis of only 100&#8239;g of muscle mass could increase potassium by 1&#8239;mEq&#47;L<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; Serum calcium levels are initially low&#44; especially in patients with kidney disease&#44; but should return to normal during the recovery phase<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a>&#46; Protease release can cause liver dysfunction in 25&#37; of patients with RML<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The release of prothrombotic substances during muscle destruction activates the coagulation cascade&#44; which can trigger disseminated intravascular coagulopathy&#44; which is a late complication &#40;12&#8722;72&#8239;h&#41;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Compartment syndrome is a serious complication often associated with muscle injuries accompanied by fracture&#44; especially in the tibia and forearm<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a>&#46; The massive entry of calcium and sodium promotes the accumulation of extracellular fluid inside the cells&#44; causing local oedema and an increase in intramuscular pressure&#44; preventing blood circulation in the area and thus intensifying the edema<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a>&#46; The characteristic symptom is greater than expected muscle pain&#44; accompanied by pallor&#44; absence of pulse and&#44; in severe cases&#44; limb ischaemia&#46;</p><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Acute renal failure</span><p id="par0120" class="elsevierStylePara elsevierViewall">Acute renal failure &#40;ARF&#41; is the most important complication of RML&#46; Its frequency is highly variable&#44; estimating figures of 10&#8211;50&#37; and a mortality also variable of 3&#8211;32&#37; that increases to more than 50&#37; in critical patients<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;53&#8211;55</span></a>&#46; Illicit drug intoxication and alcohol abuse are the aetiologies of RML most closely related to ARF<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46; The mechanism of injury leading to ARF is determined by three processes&#58; vasoconstriction&#44; ischaemia and direct tubular injury&#46; During muscle destruction&#44; intracellular fluid is sequestered into the extracellular space&#44; leading to hypovolaemia and activating the renin-angiotensin-aldosterone system&#44; which in turn increases the production of vasoconstrictor molecules and inhibits the production of prostaglandins&#44; thus decreasing renal flow<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; On the other hand&#44; myoglobin&#44; together with volume depletion and renal vasoconstriction&#44; exerts a cytotoxic effect on the nephron&#44; both directly by interacting with the Tamm-Horsfall protein&#44; as well as through the free iron released after its degradation<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;21&#44;56</span></a>&#46; The presence of acidosis enhances myoglobin nephrotoxicity through cast formation and tubular obstruction&#44; particularly in the distal convoluted tubules<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Although there is no standardised cut-off value for myoglobin that causes renal injury&#44; high myoglobin levels &#40;15&#8722;20&#8239;mg&#47;L&#41; have been reported to be associated with creatinine levels&#44; development of ARF and the need for haemodialysis<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a>&#46; No association was found between urinary myoglobin values and ARF<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a>&#46; There is no defined threshold value for CK related to the risk of ARF&#44; but its proportion increases at levels above 15&#44;000&#8239;U&#47;L and is uncertain at lower levels<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;53&#44;54</span></a>&#46; A recent review links LDH levels to worsening kidney function<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">McMahon et al&#46; proposed an ARF index in RML &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; which includes the variables age&#44; sex&#44; aetiology and initial creatinine&#44; CK&#44; phosphate&#44; bicarbonate and calcium values<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46; A McMahon score below five indicates a 2&#8722;3&#37; risk of ARF or death&#44; while a score above 10 raises the risk to 52&#8211;61&#46;2&#37;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46; Figures greater than six reflect kidney damage and&#44; according to the authors&#44; renal protection therapies would be indicated<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Etiological diagnosis</span><p id="par0135" class="elsevierStylePara elsevierViewall">Diagnostic evaluation of RML should be performed in patients with acute muscle symptoms&#44; in those with dark urine in the presence of myoglobinuria&#44; or in those with exercise intolerance &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The confirmation of RML is subject to the elevation of CK&#44; whose serialization and monitoring is necessary to know the temporal status of RML and prognosis<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;53&#44;54</span></a>&#46; Likewise&#44; CK levels stratify the severity of RML&#46; Values below 5000 U&#47;L &#40;mild RML&#41; have a low probability of developing renal involvement&#44; while those between 5&#44;000&#8211;15&#44;000&#8239;U&#47;L &#40;moderate&#41; have a high risk of renal failure and those &#62; 15&#44;000&#8239;U&#47;L &#40;severe&#41; have a high risk of dialysis<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">The clinical history and physical examination are the fundamental basis for making an aetiological diagnosis of elevated CK&#44; including personal history&#44; trauma&#44; immobilisation&#44; toxic habits&#44; treatments and symptoms that point to an infectious cause&#46; Along with CK values&#44; myoglobin values and the presence of myoglobinuria will be requested&#44; in addition to the required parameters based on the suspected aetiology such as blood gases&#44; complete blood count&#44; coagulation and toxicological study&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Muscle biopsy and electromyogram are not necessary&#44; although they can be used to confirm the diagnosis of RML and could be performed if metabolic or inflammatory myopathy is suspected<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; A muscle biopsy should wait several weeks or months after the clinical event&#44; as the results of a biopsy will not be informative in the early stages<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; When exercise intolerance or metabolic myopathy is suspected&#44; the exercise test or lactate-ammonium curve may be performed as a non-invasive diagnostic test<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a>&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Treatment</span><p id="par0150" class="elsevierStylePara elsevierViewall">When RML is suspected&#44; regardless of the cause&#44; the most important goal is to preserve renal function &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; This objective is even more important in those patients with moderate-severe RML&#44; or what is the same&#44; CK values greater than 15&#44;000 U&#47;L or a McMahon score above 10<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a>&#46; Renal prevention should be initiated as early as possible by administering fluid therapy to maintain or improve renal perfusion&#44; minimise ischaemic injury and to increase urine flow rate&#44; which will limit the formation of intratubular casts by diluting the heme pigment concentration within the tubular fluid&#44; remove partially obstructing intratubular casts and increase urinary excretion of potassium<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; It has been shown that haste in volume replacement is directly proportional to progression to ARF<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a>&#46; Although the need for volume replacement is established&#44; the composition of the fluid used for volume replacement remains controversial&#44; with no clinical trials or clear recommendations available<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>&#46; Studies with Ringer&#8217;s lactate&#44; glucose saline&#44; isotonic saline and hypotonic saline have shown benefits&#44; with no clear differences between them in terms of time to normal CK levels and favourable prognosis&#44; with individualisation of each case being paramount<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>&#46; Patients with RML may require considerable amounts of fluid therapy at an initial rate of up to 1&#46;5&#8239;L&#47;h and subsequently 300&#8722;500&#8239;mL&#47;h<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">Bicarbonate administration is aimed at alkalinisation of the urine &#40;pH&#8239;&#62;&#8239;6&#46;5&#41;&#44; in order to prevent myoglobin precipitation in the renal tubules and renal dysfunction&#46; Its use is more recommended in those patients with moderate-severe RML without hypocalcaemia&#44; with arterial pH below 7&#46;5 and serum bicarbonate below 30&#8239;mEq&#47;L<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; Its usefulness is contradictory for some authors&#44; no benefits being observed when it is administered jointly with saline compared to Ringer&#39;s lactate<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;61</span></a>&#46; The recommended dose is 44&#8211;50 mEq per 2&#8239;L of serum<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>&#46; There is no consensus on the use of mannitol&#46; Its use is recommended if fluid therapy alone does not produce a diuresis greater than 300&#8239;mL&#47;h and contraindicated in anuric patients<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; Plasma osmolarity and anion gap should be monitored during use and should be discontinued if it exceeds 55&#8239;mOsm&#47;kg<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; The administration of loop diuretics has not shown a clear improvement&#44; in addition to being able to lower urinary pH<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a>&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">An appropriate fluid management approach could start with intravenous saline solution at 1&#8239;L&#47;h&#46; Subsequently administer 500&#8239;mL of isotonic saline&#44; alternating with 500&#8239;mL of 5&#37; glucose&#44; maintaining the infusion rate at 1&#8239;L&#47;h and adding 50&#8239;mEq of bicarbonate per 2&#8722;3&#8239;L to maintain urinary pH&#8239;&#62;&#8239;6&#46;5&#46; Once diuresis has been established&#44; if it is not greater than 300&#8239;mL&#47;h&#44; it would be appropriate to administer a 20&#37; mannitol solution &#40;1&#8239;g&#47;kg&#41; for 4&#8239;h&#46; Treatment should be continued until the progressive decrease in CK levels and myoglobinuria is confirmed&#44; with special attention to the risk of fluid overload<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;60</span></a>&#46; It is recommended to control ions &#40;potassium and calcium&#41;&#44; plasma pH and electrocardiographic monitoring in the face of these abnormalities<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; The use of renal replacement therapy is limited to life-threatening electrolyte disturbances &#40;hypercalcemia&#44; hyperkalaemia&#41; that do not respond to initial treatment&#44; overhydration&#44; or in anuric renal failure<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;18&#44;62</span></a>&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusions</span><p id="par0165" class="elsevierStylePara elsevierViewall">RML is a clinical entity to be considered due to its varied aetiology and potential complications&#44; whose aetiological diagnosis is based on a good history-taking and physical examination&#46; Treatment&#44; based on volume replacement&#44; should be started early to maintain or improve renal function and avoid the most common and life-threatening complication&#44; acute renal failure&#46; The total volume required must be individualized and adjusted according to diuresis&#46; Although there is no consensus on the composition of the fluid to be used&#44; its use is even more important in patients with CK values above 15&#44;000&#8239;U&#47;L&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interests</span><p id="par0170" class="elsevierStylePara elsevierViewall">The author declares that he has no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Rhabdomyolysis is characterized by the release of intracellular elements after the destruction of skeletal muscle&#46; Is characterized by the presence of muscle pain&#44; weakness&#44; and dark urine&#44; associated with elevated creatine kinase &#40;CK&#41;&#46; The causes related to this syndrome are varied&#44; being traumatic etiology&#44; immobilization&#44; sepsis&#44; drugs and alcohol the most frequent&#46; CK values are used for diagnosis and prognosis&#44; being renal dysfunction the most serious complication&#46; Treatment is based on early and intensive fluid therapy to avoid kidney complications&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La rabdomi&#243;lisis es una entidad cl&#237;nica caracterizada por la liberaci&#243;n de elementos intracelulares tras la destrucci&#243;n del m&#250;sculo esquel&#233;tico&#46; La tr&#237;ada cl&#225;sica se caracteriza por la presencia de dolor muscular&#44; debilidad y orina oscura&#44; asociada a elevaci&#243;n de la creatincinasa &#40;CK&#41;&#46; Las causas relacionadas con este s&#237;ndrome son variadas&#44; siendo la etiolog&#237;a traum&#225;tica&#44; inmovilizaci&#243;n&#44; sepsis&#44; drogas&#44; f&#225;rmacos y alcohol&#44; las m&#225;s frecuentes&#46; Los valores de CK son utilizados como diagn&#243;stico y pron&#243;stico&#44; siendo la disfunci&#243;n renal la complicaci&#243;n m&#225;s grave&#46; El tratamiento se basa en la fluidoterapia intensiva y precoz para evitar complicaciones renales&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Baeza-Trinidad R&#46; Rabdomi&#243;lisis&#58; un s&#237;ndrome a tener en cuenta&#46; Med Clin &#40;Barc&#41;&#46; 2022&#59;158&#58;277&#8211;283&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evaluation for suspected rhabdomyolysis&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CK&#58; creatine kinase&#59; U&#47;L&#58; units&#47;litre&#59; RML&#58; rhabdomyolysis&#46;</p>"
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            "rol" => "short"
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pharmacological group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antipsychotics&#47;antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amitriptyline&#44; fluoxetine&#44; haloperidol&#44; lithium&#44; chlorpromazine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypnotics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Benzodiazepines&#44; barbiturates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antihistamines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diphenylamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anaesthetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Succinylcholine&#44; propofol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lipid-lowering agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Statins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ezetimibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fibrates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antibiotics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polymyxins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oxazolidinones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lipopeptides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antitubercular agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Protein synthesis inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Quinolones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Macrolides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Colistin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Co-trimoxazole&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antivirals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Protease inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Integrase inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nucleoside reverse transcriptase inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oseltamivir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nucleoside analogues&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiparasitics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antimalarials&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amphotericin B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiprotozoals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glucocorticoids&#44; colchicine&#44; quinidine&#44; salicylates&#44; thiazides&#8230;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Drugs related to rhabdomyolysis&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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            "identificador" => "at0015"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A score &#60;5 indicates a low risk of renal failure or death and &#62;6 indicates the need for renal protective therapy&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">CK&#58; creatine kinase&#59; mg&#47;dL&#58; milligrams&#47;decilitre&#59; U&#47;L&#58; units&#47;litre&#59; mEq&#47;L&#58; milliequivalents&#47;litre&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>50&#8722;70 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>70&#8722;80 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62;80 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Baseline creatinine</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&#46;4&#8722;2&#46;2&#8239;mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62; 2&#46;2&#8239;mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Baseline calcium &#60;7&#46;5&#8239;mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Initial CK &#62;40&#44;000&#8239;U&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Aetiology other than seizures&#44; syncope&#44; exercise&#44; statins&#44; or myositis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Initial phosphate</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4&#8722;5&#46;4&#8239;mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62; 5&#46;4&#8239;mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Initial bicarbonate &#60;19&#8239;mEq&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  """
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Variables of the acute renal failure score in rhabdomyolysis<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">RML&#58; rhabdomyolysis&#59; mL&#58; millilitres&#59; mEq&#58; milliequivalents&#59; mOsm&#58; milliosmoles&#59; RRT&#58; renal replacement therapy&#46;</p>"
          "tablatextoimagen" => array:1 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fluid therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Premature and intense volume replacement&#44; especially in moderate-severe RML&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Administration of fluid therapy at a rate of 1&#8239;L&#47;h &#40;for example&#44; in the initial phases saline solution and later combination with dextrose solution&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Depending on diuresis and progression&#44; reduce to 300&#8722;500&#8239;mL&#47;h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Consider the administration of loop diuretics in overhydration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bicarbonate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">50&#8239;mEq&#47;L in every 2&#8722;3&#8239;L of fluid therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Recommended especially in moderate-severe rhabdomyolysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">The goal is to achieve urinary pH values &#62; 6&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Limit its use if hypocalcaemia&#44; arterial pH&#8239;&#60;&#8239;7&#46;5 or serum bicarbonate &#60;30&#8239;mEq&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mannitol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">There is no consensus on its use&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recommended use if an initial diuresis of 300&#8239;mL&#47;h is not achieved&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Administration of 1&#8239;g&#47;kg for 4&#8239;h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Contraindicated in anuric patients and discontinue if anion gap &#62;55&#8239;mOsm&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RRT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Use in electrolyte abnormalities that do not respond to conservative management&#44; overhydration or anuria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Treatment of rhabdomyolysis&#46;</p>"
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        0 => array:2 [
          "identificador" => "bibs0005"
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            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rhabdomyolysis and acute kidney injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "X&#46; Bosch"
                            1 => "E&#46; Poch"
                            2 => "J&#46;M&#46; Grau"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra0801327"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2009"
                        "volumen" => "361"
                        "paginaInicial" => "62"
                        "paginaFinal" => "72"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19571284"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
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                ]
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              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Crush injuries with impairment of renal function"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46;G&#46; Bywaters"
                            1 => "D&#46; Beall"
                          ]
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Br Med J"
                        "fecha" => "1941"
                        "volumen" => "1"
                        "paginaInicial" => "427"
                        "paginaFinal" => "432"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20792797"
                            "web" => "Medline"
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                    ]
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            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Crush injury with renal failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46; Beall"
                            1 => "E&#46;G&#46; Bywaters"
                            2 => "R&#46;H&#46; Belsey"
                            3 => "J&#46;A&#46; Miles"
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                    0 => array:2 [
                      "doi" => "10.1136/bmj.1.6058.432"
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                        "tituloSerie" => "Br Med J"
                        "fecha" => "1941"
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                        "paginaInicial" => "432"
                        "paginaFinal" => "434"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/138470"
                            "web" => "Medline"
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              "identificador" => "bib0020"
              "etiqueta" => "4"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The syndrome of rhabdomyolysis&#58; pathophysiology and diagnosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G&#46;D&#46; Giannoglou"
                            1 => "Y&#46;S&#46; Chatzizisis"
                            2 => "G&#46; Misirli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ejim.2006.09.020"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Intern Med"
                        "fecha" => "2007"
                        "volumen" => "18"
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