Rhabdomyolysis Advances In Diagnosis And Treatment Pdf

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Rhabdomyolysis is a condition in which skeletal muscle tissue dies, releasing substances into the blood that cause kidney failure. Rhabdomyolysis is usually caused by a specific event. This is most commonly injury, overexertion, infection, drug use, or the use of certain medications.

Rhabdomyolysis is a common cause of acute kidney injury, featuring muscle pain, weakness and dark urine and concurrent laboratory evidence of elevated muscle enzymes and myoglobinuria. Rhabdomyolysis is often seen in elderly and frail patients following prolonged immobilization, for example after a fall, but a variety of other causes are also well-described. What is unknown to most physicians dealing with such patients is the fascinating history of rhabdomyolysis.

2017, Number 5

Rhabdomyolysis is a common cause of acute kidney injury, featuring muscle pain, weakness and dark urine and concurrent laboratory evidence of elevated muscle enzymes and myoglobinuria. Rhabdomyolysis is often seen in elderly and frail patients following prolonged immobilization, for example after a fall, but a variety of other causes are also well-described. What is unknown to most physicians dealing with such patients is the fascinating history of rhabdomyolysis.

Cases of probable rhabdomyolysis have been reported since biblical times and during antiquity, often in the context of poisoning. Equally interesting is the link between rhabdomyolysis and armed conflict during the 20th century.

Salient discoveries regarding the pathophysiology, diagnosis and treatment were made during the two world wars and in their aftermath. As a specialty, we have also learned a lot about the disease from 20th-century earthquakes, and networks of international help and cooperation have emerged.

Finally, rhabdomyolysis has been described as a sequel to torture and similar forms of violence. Clinicians should be aware that rhabdomyolysis and the development of renal medicine are deeply intertwined with human history. Most cases are caused by trauma, prolonged immobilization or extreme physical exertion [ 2 ].

Acute kidney injury AKI is one of the most severe complications of rhabdomyolysis. AKI in rhabdomyolysis often leads to rapid release of potassium and phosphate from muscle, leading to a need for higher doses of renal replacement therapy RRT than is required for other forms of AKI. The diagnosis is often straightforward, usually when there is an obvious cause such as prolonged immobilization or trauma. Common and unusual causes of rhabdomyolysis are well known to nephrologists and to renal faculty, and are also regularly taught during ward rounds and in case presentations.

What is much less known even among seasoned renal educators is the fascinating and thought-provoking history of rhabdomyolysis from biblical times to the late 20th century. None of them is published in a journal within our own specialty.

Here, we provide a brief review of the history of rhabdomyolysis for the clinical nephrologist and for use during teaching. We describe interesting causes of rhabdomyolysis throughout human history, highlight ethical dilemmas and describe how historical events helped our specialty diagnose, understand and treat AKI caused by rhabdomyolysis. Adapted from Vanholder et al. The first albeit vague mention of possible rhabdomyolysis is often credited to the Bible.

A wind sent by the Lord came up and blew quail in from the sea; it dropped them all around the camp … The people were up all that day and night and all the next day gathering the quail … and they spread them out all around the camp. Coturnix coturnix common quail. Quail poisoning coturnism is a well-described cause of rhabdomyolysis [ 24 ], although perhaps most nephrologists will be unaware of the link. Toxins ingested with contaminated quail meat are believed to be the cause [ 25 ].

Whether the toxins are from hemlock or other plants such as henbane Hyoscyamus niger or red hemp nettle Galeopsis ladanum [ 26 ] is not entirely clear [ 27 ]. Coturnism is well described in antiquity [ 27 ] and has been reported from around the Mediterranean throughout the 20th century, usually in fall when the bird migrates in large numbers [ 24 ]. Rhabdomyolysis is a key feature of coturnism [ 24 ] and some authors have suggested a genetic background that confers vulnerability to the toxin [ 28 ].

Much of our knowledge stems from the detailed description of the condition by Edmond Sergent in the s [ 29 , 30 ]. Sergent, who at the time worked as director of the Morocco Institut Pasteur in Casablanca, described the case of an Algerian hunter who had previously eaten quail without incident but then developed severe symptoms after another meal involving quail [ 30 ].

Others have suggested that Sergent viewed the biblical quail incident as one of transcendent mystery and they note that some questions around coturnism remain unresolved to the present day [ 30 ].

A similar condition has been reported from Italy following consumption of skylarks, chaffinches and robins that have ingested plants from the hemlock family in spring [ 31 ]. Of note, the birds themselves are not susceptible to the active alkaloids and they are heat stable. Other biblical accounts of poisoning have been linked to hemlock as well. Davies and Davies speculated whether the sudden and otherwise unexpected death of two healthy young priests could be explained by their having inhaled incense contaminated with hemlock [ 32 ].

The use of plants from the hemlock family as a poison goes far back in time. As a medicine, hemlock has multiple properties and was used since antiquity well into the 18th century for a variety of conditions including cancer [ 33 ] and whooping cough [ 34 ].

In trying to link muscular toxicity to hemlock, it is important to appreciate that hemlock species are a member of the order Umbelliferae, which also includes many edible plants such as carrot, fennel and parsnip.

There is often confusion between water hemlock species Cicuta and Oenanthe and poison hemlock Conium maculatum [ 36 ]. Many symptoms overlap but differentiation between the two is important. Cicuta spp. In contrast, C. Rhabdomyolysis is described in conjunction with both water [ 36 ] and poison [ 40 ] hemlock and occurs due to seizure-induced muscle injury or as a result of direct myotoxicity. Roots of water hemlock are ingested by mistake for their sweet taste, which has been described as pleasant and similar to wild parsnip or wild carrot.

Spotted water hemlock Cicuta maculata , from Clark and Fletcher [ 37 ] image in the public domain. To the best of our knowledge, the first description of rhabdomyolysis in war dates back to when Larrey, the great military surgeon of the Napoleonic army, described muscle necrosis in carbon monoxide poisoning during the occupation of Berlin [ 41 ]. Carbon monoxide remains a well-described cause of rhabdomyolysis to the present day [ 42 ]. It is often German surgeon Ludwig Frankenthal — who is credited with the first report of traumatic rhabdomyolysis and AKI caused by war injuries, but this occurred almost a century later than Lerry's account, in [ 43 ].

A few years later, Minami, a Japanese dermatologist who studied in Germany, under the supervision of the German pathologist, Professor Ludwig Pick, described the kidneys of three German soldiers who died of traumatic injuries during World War I and suspected muscle damage as a likely culprit of the ensuing renal failure [ 44 ]. In his conclusion Minami states. Despite such detailed reports of crush syndrome and its complications and a well-developed concept of pathogenesis in the German literature, the Allies entered World War II more or less oblivious of its existence.

It was Eric Bywaters — , a Hammersmith hospital rheumatologist [ 45 ], who in rediscovered the syndrome in victims of the London Blitz [ 46 ].

Fifty years later Bywaters commented:. History … teaches us that man does not learn from history. In hindsight, it is quite remarkable that until Bywaters' publication this potentially lethal entity was largely unknown to the British and American medical literature, including textbooks of military medicine [ 48 ].

It is noteworthy that the official German military medical account of World War I described as many as cases with this syndrome [ 49 , 50 ].

All four patients died in about a week with nitrogen retention and necropsy revealing pigment casts, polymorphonuclear invasion and acute tubular necrosis [ 46 ]. Blood transfusion was initially considered as a contributing factor. However, Mayon-White and Solandt, describing a similar patient who had never received blood, refuted this assumption [ 51 ].

In , using animal models, Bywaters and Stead identified myoglobin as the offending agent and formulated a treatment plan. Their approach involved vigorous rehydration preferably starting at the site of accident and alkalization of urine with the purpose of decreasing myoglobin precipitation in the renal tubules [ 52 ]. From Bywaters [ 47 ], with permission. Rhabdomyolysis has remained an important topic in military medicine during more recent armed conflict.

In their seminal paper, Fitts et al. The authors emphasize that due to the advent of dialysis more patients with rhabdomyolysis may survive, and also recommend intravenous fluids even before the crushed limbs are released [ 53 ]. A lot of experience was also gathered during the Lebanon war in the s [ 54 ]. Contemporary guidelines on the management of crush injury on the battlefield emphasize the early use of intravenous fluids [ 55 ].

However, even on 20th-century battlefields, rhabdomyolysis is associated with mortality as described in recent studies of the Iraq and Afghanistan wars [ 56 ].

A witness described the scenery in one of the coastal villages as follows:. It was an unbelievably saddening thing to watch: Strong men being carried from their fishing boats to their homes — completely stiff and utterly helpless. The fact that the victims were usually fishermen immediately intrigued both public health officials and researchers, and a toxin in the aquatic food chain was suspected more or less immediately.

The disease was observed only in summer and fall and only on the coast of this particular part of the Baltic Sea, where it occurred in epidemics, small clusters or sporadically [ 59 , 60 ].

Several toxins were proposed as possible causes [ 61 ]. One hypothesis assumed that arsenic-containing waste derived from the nearby chemical industry led to the formation of arsenic gas just above the water surface, which was then inhaled by the victims during early morning fishing trips [ 58 ].

At some stage gas masks were issued to fishermen. Eventually, no further cases were observed although the reasons for its disappearance remained as enigmatic as its actual cause [ 55 ]. Haff disease still occurs [ 61—63 ], often associated with crayfish, but the exact nature of the toxin in the aquatic food chain remains unknown to the present day [ 64 ].

Mushroom poisoning is another cause of rhabdomyolysis that has emerged in the 20th century. A recent classification of mushroom poisoning proposed by White et al. There are reports of Russula subnigricans causing delayed-onset rhabdomyolysis with AKI in the severely poisoned patient [ 66 ]. Tricholoma equestre is known under various names and is consumed throughout the world. Since there are controversial opinions on its edibility and ability to cause rhabdomyolysis [ 67 ], a group of French authors investigated the rhabdomyolysis apparently induced in 12 humans by several consecutive meals of T.

They concluded that a genetic muscular susceptibility was a probable key factor for sometimes severe rhabdomyolysis to develop in individuals after repeated consumption of T. Another interesting cause of rhabdomyolysis also became evident in the late 20th century: genetic disorders.

A typical patient develops rhabdomyolysis after moderate exercise in a scenario that one would not normally associate with rhabdomyolysis [ 69 ]. A whole host of genetic conditions that predispose to rhabdomyolysis have now been identified, many of which are mitochondrial [ 70 ]. A more recent discovery is that mutations in the ryanodine receptor 1 gene predispose to rhabdomyolysis and also, interestingly, to malignant hyperthermia [ 71 ]. The diagnosis of an inherited myopathy in a patient with rhabdomyolysis requires a high degree of suspicion and often involves muscle biopsies and tests in specialized centres.

Even other forms of rhabdomyolysis may have a more subtle genetic background [ 70 ]. The history of rhabdomyolysis is not limited to war and human conflict; crush injury also takes its toll in peacetime.

Natural disasters such as earthquakes, hurricanes, tsunamis and cyclones are now well appreciated as a cause of rhabdomyolysis, and the term 'disaster nephrology' [ 72 ] has been coined. In addition, seismo-nephrology [ 72 ] relates specifically to earthquake-associated renal injury. From Tattersall et al. B Improvised dialysis facility using the NxStage device following the Haiti earthquake.

As a renal community, we have learned a considerable amount about the pathogenesis of AKI and crush syndrome in earthquake victims. Rhabdomyolysis can occur either as a sequel to crush injury from direct trauma or due to the ischaemia reperfusion injury that occurs when there is restoration of blood flow once victims are extracted from the rubble. Both mechanisms can coexist. The crush syndrome is the second most common cause of death in earthquake victims after asphyxia [ 72 ].

While rhabdomyolysis is the primary cause of AKI in these patients, there are other possible pre- and post-renal causes such as hypovolaemia from blood loss or dehydration, as well as direct trauma to the kidneys and urinary tract. This concept had been proposed first in the s and later reiterated following the Vietnam War [ 55 ], but the regime for fluid administration has evolved considerably and in parallel to growing experience with rhabdomyolysis overall.

Rhabdomyolysis: advances in diagnosis and treatment.

Vascular injury is a rare complication of femoral shaft fractures, and rupture of the deep femoral artery is more difficult to diagnose because of its anatomical location and symptoms. Despite its low incidence, deep femoral artery rupture can lead to life-threatening outcomes, such as compartment syndrome, making early identification and diagnosis critical. A year-old male patient was admitted to our hospital due to right lower limb trauma in a car accident, with complaints of severe pain and swelling on his right thigh. X-ray demonstrated a right femoral shaft fracture. During preparation for emergency surgery, his blood pressure and blood oxygen saturation dropped, and sensorimotor function was lost.

Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. Corpus ID: Rhabdomyolysis: advances in diagnosis and treatment. Care and C. Care , C. Tainter Published Medicine Emergency medicine practice.

Rhabdomyolysis is a potentially life-threatening condition caused by a breakdown of skeletal muscle and the release of the intracellular contents into the.

What's to know about rhabdomyolysis?

THE relationship between hypermetabolic exertional stress injuries and malignant hyperthermia MH has been a topic of debate for almost 30 yr. Central to this debate is the idea that some MH susceptible MHS patients may develop awake nonanesthesia-related manifestations similar to that seen in porcine stress syndrome. An individual is identified as MHS if he or she has a well-documented clinical episode consistent with MH during exposure to any of the known anesthetic triggering agents, or if he or she has undergone a skeletal muscle biopsy with a positive diagnostic contracture test. However, none of the published reports of patients who presented first with ER and who were subsequently identified as MHS by a positive contracture test ever developed documented clinical MH episodes involving anesthesia.

What's to know about rhabdomyolysis?

It was created in December with the purpose of disseminating scientific information derived from primary and secondary research and presenting cases coming from the practice of Rheumatology in Latin America. Since its foundation, the Journal has been characterized by its plurality with subjects of all rheumatic and osteomuscular pathologies, in the form of original articles, historical articles, economic evaluations, and articles of reflection and education in Medicine.

Rhabdomyolysis: advances in diagnosis and treatment

Rhabdomyolysis is a potentially life-threatening condition caused by a breakdown of skeletal muscle and the release of the intracellular contents into the circulatory system. There are many possible causes, including crush injury, excessive muscular activity, medications, infections, and varied metabolic, connective tissue, rheumatologic, and endocrine disorders. Optimal crystalloid selection is still debated, but immediate, aggressive intravenous volume expansion is indicated to prevent myoglobinuric renal failure. Serum potassium levels must be obtained and electrocardiograms must be evaluated to identify life- and limb-threatening complications of hyperkalemia.

Key words:. Update review of the acute porphyrias. Br J Haematol ; 4 Role of genetic testing in the management of patients with inherited porphyria and their families.

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