Heroin addict with gangrene of the extremities , rhabdomyolysis and severe hyperkalemia

Introduction. Long-time consumption of narcotics leads to altered mental status of the addict. It is also connected to damages of different organic systems and it often leads to appearance of multiple organ failure. Excessive narcotics consumption or abuse in a long time period can lead to various consequences, such as atraumatic rhabdomyolysis, acute renal failure and electrolytic disorders. Rhabdomyolysis is characterized by injury of skeletal muscle with subsequent release of intracellular contents, such as myoglobin, potassium and creatine phosphokinase. In heroin addicts, rhabdomyolysis is a consequence of the development of a compartment syndrome due to immobilization of patients in the state of unconsciousness and prolonged compression of extremities, direct heroin toxicity or extremities ischemia caused by intraluminal occlusion of blood vessels after intraarterial injection of heroin. Severe hyperkalemia and the development of acute renal failure require urgent therapeutic measures, which imply the application of either conventional treatment or a form of dialysis. Case report. We presented a male patient, aged 50, hospitalized in the Emergency Center Kragujevac due to altered mental status (Glasgow Coma Score 11), partial respiratory insufficiency (pO2 7.5 kPa, pCO2 4.3 kPa, SpO2 89 %), weakness of lower extremities and atypical electrocardiographic changes. Laboratory analyses, carried out immediately after the patient’s admission to the Emergency Center, registered the following disturbances: high hyperkalemia level (K+ 9.9 mmol/L), increased levels of urea (30.1 mmol/L), creatinine (400 mol/L), creatine phosphokinase – CK (120350 IU/L), CK-MB (2500 IU/L) and myoglobin (57000 g/L), with normal levels of troponin I (< 0.01 g/L), as well as signs of anemia (Hgb 92 g/L, Er 3.61 1012/L), infection (C-reactive proteine 184 g/mL, Le 16.1 109/L) and acidosis (base excess – 18.4 mmol/L, pH 7.26. Initial examination of the patient revealed swelling and paleness of the right lower leg, signs of gangrene of the right foot and the 1st and the 4th toes of the left foot. The patient had normal values of arterial pressure (130/80 mmHg) and heart rate (64/min-1); roentgenographic lungs examination and computerized tomography (CT) brain examination did not reveal pathological changes in lung and brain parenchyma; toxicological analyses confirmed the presence of heroin in patient’s organism. The patient was treated by intensive conventional treatment (infusion of crystalloid solutions, 8.4% solution of sodium bicarbonate, iv infusion of diuretics, calcium gluconate and short-acting insulin), and also by antibiotics and anticoagulants. Normalization of kalemia and fast regression of electrocardiographic changes were registered. The patient refused the suggested surgical treatment (fasciotomy, foot amputation). After stabilization of kidney function and improvement of his mental state, the patient agreed to undergo surgical procedure. Therefore, on the day 30 of hospitalization the above-knee amputation of the right leg was performed, and on the day 38 the transmetatarsal amputation of the left foot was carried out. After 46 days of hospital treatment, the patient was released and sent to home treatment. Conclusion. The routine laboratory diagnostics, which implies determining of the levels of potassium, urea, creatinine and CK in the serum of all hospitalized heroin addicts can contribute to timely detection of hyperkalemia and acute kidney weakness and undertaking of appropriate therapeutic measures.

proteine 184 g/mL, Le 16.1 10 9 /L) and acidosis (base excess -18.4 mmol/L, pH 7.26.Initial examination of the patient revealed swelling and paleness of the right lower leg, signs of gangrene of the right foot and the 1st and the 4th toes of the left foot.The patient had normal values of arterial pressure (130/80 mmHg) and heart rate (64/min -1 ); roentgenographic lungs examination and computerized tomography (CT) brain examination did not reveal pathological changes in lung and brain parenchyma; toxicological analyses confirmed the presence of heroin in patient's organism.The patient was treated by intensive conventional treatment (infusion of crystalloid solutions, 8.4% solution of sodium bicarbonate, iv infusion of diuretics, calcium gluconate and short-acting insulin), and also by antibiotics and anticoagulants.Normalization of kalemia and fast regression of electrocardiographic changes were registered.The patient refused the suggested surgical treatment (fasciotomy, foot amputation).After stabilization of kidney function and improvement of his mental state, the patient agreed to undergo surgical procedure.Therefore, on the day 30 of hospitalization the above-knee amputation of the right leg was performed, and on the day 38 the transmetatarsal amputation of the left foot was carried out.After 46 days of hospital treatment, the patient was released and sent to home treatment.Conclusion.The routine laboratory diagnostics, which implies determining of the levels of potassium, urea, creatinine and CK in the serum of all hospitalized heroin addicts can contribute to timely detection of hyperkalemia and acute kidney weakness and undertaking of appropriate therapeutic measures.

Introduction
Upper normal levels of potassium (4.5-5.4 mmol/L), regardless the presence of other diseases, are associated with the increase of cardiovascular mortality 1 .The risk of appearance of "malignant" cardiac arrhythmia and cardiac arrest rises with the increase of potassium concentration in serum, and for kalemia level above 9 mmol/L the undertaken therapeutic measures do not always give positive result.Narcotics abuse is among less frequent causes of hyperkalemia occurrence.Opiates, psychotropic medications, alcohol and analgesics represent substances which are often abused.In different ways, both directly and indirectly, they lead to disturbance of organic systems functioning and to appearance of diseases 2 .In addition to common complications which occur at long-term heroin consumption and heroin overdosing, such as disorders of consciousness, respiratory depression and altered mental functions, these patients may develop numerous neurologic disorders and rhabdomyolysis [3][4][5] .Severe atraumatic rhabdomyolysis results in a release of intracellular contents and subsequent increase of potassium and myoglobin concentration in serum 6 .Myoglobinuria leads to development of acute renal weakness which must be treated in intensive care units by applying either conventional treatment or a form of dialysis 4,5 .

Case report
A male patient, aged 50, was hospitalized in the Emergency Center due to altered mental status (Glasgow Coma Score 11), respiratory insufficiency (pO 2 7.5 kPa, pCO 2 4.3 kPa, SpO 2 89%), weakness of lower extremities and electrocardiogram changes (Figure 1).Ten hours prior to that, the patient had been admitted to the Psychiatric Clinic with altered mental status (Glasgow Coma Score 10) and suspected heroin overdosing.After the initial examination, there were no indications for application of antidotes, while the signs of severe electrolytic disorders were the reason for continuing the patient's treatment in the Emergency Center.
The patient had been treated in the Psychiatric Clinic for heroin addiction for approximately four previous years by methadone application (prior to the beginning of treatment, the patient had been a heroin user for 15 years).The patient demonstrated a lack of motivation for undergoing detoxication treatment (methadone application), and during previous hospitalization in the Psychiatric Clinic (three months earlier), signs of renal weakness of the second degree (levels of urea of 11.6 mmol/L and creatinine of 145 mol/L) and initial right foot ischemia had been registered in the patient.).Until the admission to the Emergency Center, the patient had oliguria (diuresis lower than 20 mL/hr) and initial laboratory analyses revealed severe hyperkalemia (K + 9.9 mmol/L), increased levels of urea (30.1 mmol/L), creatinine (400 mol/L), creatinine phosphokinase -CK (120350 IU/L), CK-MB (2500 IU/L) and myoglobin (57000 g/L), with normal levels of troponin I (< 0.01 g/L).The elevated levels of aspartate transaminase (AST) -720 IU/L, alanine aminotransferase (ALT) -235 IU/L and lactate dehydrogenase (LDH) -3860 IU/L were registered in the patient's serum, with normal values of bilirubin.The initial concentration of fibrin degradation fragment (d-Dimer) in the patient's serum was 2970 g/L, and prolongation of prothrombin time (INR 1.8) was registered as well.The presence of anti-HCV antibodies was registered in the patient's serum, and toxicological analyses (rapid immunochromatographic Bio Gnost ® assay) revealed the presence of heroin, methadone and benzodiazepines in patient's organism.Radiographic lungs examination and computerized tomography (CT) brain examination did not reveal pathological changes in the lung and brain parenchyma.Ultrasound examination of right leg arteries revealed sclerotic changes of walls and locally calcified lesions on femoral artery, with normal flow all the way to its distal parts.From that part, distally, in popliteal and tibial arteries the flow was not registered; instead, a complete occlusion of those arteries by hyperechogenic thrombi (old thrombosis) was detected.The patient was treated by intensive conventional treatment (infusion of crystalloid solutions, 8.4% solution of sodium bicarbonate, iv infusion of diuretics, calcium gluconate and short-acting insulin), and also by antibiotics and anticoagulants.There was no need for applying mechanical ventilation; instead, oxygen was applied by nasal catheter.During the first 24 hours of hospitalisation in the Emergency Center, mental status was normalised, as well as values of arterial blood gasses.Since the registered diuresis was satisfactory, with gradual decrease of kalemia (Table 1) and rapid regression of electrocardiographic changes (Figure 2), the application of a form of dialytic treatment was abandoned.From the 7th until the 23rd day of hospitalization the patient was treated in the Clinic for Urology and Nephrology.Ultrasound examination did not reveal any changes of position, size and shape of kidneys, but the presence of bilateral calculosis was observed.On the 8th day of hospitalization, creatinine clearance was 22 mL/min.Despite the existing gangrene on lower extremities, on the tenth day of hospitalization the decrease of CK to the level below 500 IU/L was registered.The patient kept refusing the suggested surgical treatment, although he was treated in the Center for Cardiovascular Surgery since the 23rd day of hospitalization.After stabilisation of the patient's mental status, he agreed to undergo the suggested surgical procedure.Therefore, on the 30th day of hospitalization above-knee amputation of the right leg was performed, and on the 38th day the transmetatarsal amputation of  the left foot was carried out.After 46 days of hospital treatment, the treatment was continued in home environment.

Discussion
Heroin addiction leads to nervous system damages, as a consequence of psychic functions disturbance, and also to numerous, seemingly unusual somatic disorders.Acute rhabdomyolysis is a syndrome which rarely occurs, but since it involves injuries of integrity of muscle cells plasma membrane and release of toxic intracellular contents into the circulatory system, it is characterised by potentially serious complications 6,7 .Rhabdomyolysis may occur due to excessive physical exertion, muscle injury, endocrinologic disorders, infections and exposure to various medications and toxins 3,4 .
Pathophysiology of rhabdomyolysis associated with heroin addicts is obscure.Most authors who study this disorder indicate that pathogenesis of rhabdomyolysis is multifactorial and that it occurs either due to acidosis, hypoxia, muscle compression, direct toxicity and immunologic reactions caused by heroin and various contaminants or due to infections or blood vessels damage caused by intravenous / intraarterial injection of heroin 5,6,[8][9][10][11] .
Approximately one third of patients with rhabdomyolysis develop acute renal failure 12 .Unlike pathophysiologic mechanisms cocaine overdosing, where vasospasm of renal arteries and malignant hypertension are responsible for the development of renal insufficiency, heroin, through rhabdomyolysis, leads to massive myoglobinuria, renal tubules obstruction and development of acute renal failure 3,13 .These patients develop hyperkalemia due to release of potassium from myocytes and the development of acute renal failure.Besides conventional treatment, hyperkalemia often calls for application of some form of dialysis (continuous venovenous dialysis, hemofiltration or hemodiafiltration) 12 .The fact that only in the United States of America there are around 100,000 new registered heroin users in a year emphasizes the importance of treating acute and chronic complications caused by heroin consumption 2 .
Hyperkalemia is a potentially fatal condition and is defined as a concentration of potassium higher than 5.5 mmol/L.The risk of appearance of cardiac arrhythmia is directly dependent on hyperkalemia level.In extreme hyperkalemia, fatal arrhythmias such as ventricular fibrillation and asystole are often registered.However, with the application of adequate therapy, the fatal outcome can be avoided even in patients with serum potassium concentration above 10 mmol/L 14 .In patients with severe hyperkalemia electrocardiograms can be different -from normal electrocardiographic records to records which may imitate the existence of ventricular tachycardia or myocardial infarction 15,16 .Therefore, severe hyperkalemia must be treated in line with its etiology and accompanying disorders.
Our patient had the signs of severe hyperkalemia and acute renal failure.During previous hospitalizations in the Psychiatric Clinic, signs of foot ischemia and renal function decline had been registered in the patient.Since the patient was a long-time heroin addict, he had most probably developed heroin nephropathy over the years.American authors point out the fact that long-time consumption of cocaine and heroin leads to development of chronic renal failure through the appearance of segmental glomerulosclerosis and membranoproliferative glomerulonephritis 2 .
In addition to that, long-time intravascular application of heroin and other drugs leads, initially, to damage of small diameter veins, and, over time, damage of large diameter veins and arteries; therefore, in addition to vasospasm, heroin addicts develop many vascular complications on extremities blood vessels, ranging from trombophlebitis, aneurysms and arteriovenous fistulas to occlusions of blood vessels by thrombus or embolus 10,17 .
A preexisting renal failure in our patient, his rejection of addiction treatment by application of methadone and recurring use of heroin resulted in the appearance of severe somatic disorders, such as extremities ischemia, rhabdomyolysis, acute renal failure and potentially fatal hyperkalemia.Aggressive application of infusion solutions, urine alkalization and acidosis correction led to stabilization of renal function and correction of electrolytic disorders even without dialytic treatment.Normal troponin levels, regardless of enormously high CK levels, as well as rapid regression of electrocardiographic changes made possible the exclusion of the presence of acute coronary syndrome.Surgical treatment was suggested (extremity amputation), which the patient accepted only after intensified psychiatric treatment.
In this paper, we have shown that timely application of conventional treatment of severe hyperkalemia in heroin addict with preexisting renal failure and gangrene of the extremities may result in rapid regression of electrocardio-

Conclusion
Consumption of heroin may lead to rhabdomyolysis and myoglobinuria, subsequent renal function decline and severe hyperkalemia which sometimes results in sudden appearance of asystole and fatal outcome.The routine laboratory diagnostics which implies determining of the levels of potassium, urea, creatinine and creatine phosphokinase in serum of all hospitalized heroin addicts can contribute to well-timed detection of these severe complications and undertaking of appropriate therapeutic measures.

R E F E R E N C E S
RM, et al.Vojnosanit Pregl 2012; 69(10): 908-912.Pathological findings were not registered by the initial physical examination of heart and lungs during hospitalization in the Emergency Center.The patient had normal values of arterial pressure (130/80 mmHg) and heart rate (64/min -1 ).Swelling and paleness of the right lower leg, as well as the signs of gangrene of the right foot and the 1st and the 4th toes of the left foot, were registered in the patient.Laboratory analyses revealed signs of anemia (Hgb 92 g/L, Er 3.61 10 12 /L), infection (creactive protein -CRP 184 g/mL, Le 16.1 10 9 /L) and acidosis (base excess -18.4 mmol/L, pH 7.26

Fig 1 .
Fig 1. -Electrocardiogram at admission -decreased P-wave amplitude, extremely expanded QRS complexes -above 0.16 s and increased T wave amplitude