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Successful use of extracorporeal blood purification in treating severe cocaine-induced rhabdomyolysis
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Abstract Background Septic shock, a leading cause of acute kidney injury, induces release of pro-/anti-inflammatory mediators, leading to increased mortality and poor renal recovery. This is the first in vitro study directly comparing three single-use blood purification devices in terms of removing sepsis-associated mediators and endotoxins. Methods In vitro hemoperfusion was performed using oXiris®, CytoSorb®, and Toraymyxin®. Heparinized human plasma from healthy volunteers was pre-incubated with pathologic quantities of inflammatory mediators and filtered in a closed-loop circulation model for 2 h. For each device, the removal of 27 inflammatory mediators was measured over time. Endotoxin removal mediated by oXiris and Toraymyxin was assessed using hemoperfusion over 6 h. Results Endotoxin (lipopolysaccharide) removal was most rapid with Toraymyxin; mean adsorptive clearance over the first 30 min was ~ 20 ml/min vs ~ 8 ml/min with oXiris (p
Rhabdomyolysis, a clinical syndrome caused by damage to skeletal muscle and release of its breakdown products into the circulation, can be followed by acute kidney injury (AKI) as a severe complication. The belief that the AKI is triggered by myoglobin as the toxin responsible appears to be oversimplified. Better knowledge of the pathophysiology of rhabdomyolysis and following AKI could widen treatment options, leading to preservation of the kidney: the decision to initiate renal replacement therapy in clinical practice should not be made on the basis of the myoglobin or creatine phosphokinase serum concentrations.
Rhabdomyolysis and acute renal failure after cocaine overdose. Report of one case Rhabdomyolysis caused by cocaine abuse is multifactorial, involving tissue ische-mia secondary to vasoconstriction and cellular damage caused by the drug. Renal failure may or may be not associated to rhabdomyolysis. We report a 41-year-old male admitted with a severe rhabdomyolysis after a cocaine overdose. In spite of a vigorous hydration and alkalization, he developed acute renal failure. Renal function recovered after several weeks of dialysis. (Rev Med Chile 2011; 139: 480-483).
Cocaine has been associated with known adverse effects on cardiac, cerebrovascular and pulmonary systems. However, the effect of cocaine on other organs has not been extensively reported. A middle age man presented with abdominal pain and nausea after inhalation of crack cocaine. On admission, he was found to be hypertensive and tachycardic. Physical examination revealed mild abdominal tenderness without rebound. Laboratory investigations were significant for acute kidney failure with elevated serum creatinine (3.72 mg/dL), thrombocytopenia (platelet count 74,000/UL), elevated alanine and aspartate transaminases (ALT 331 U/L; AST 462 U/L) and elevated creatine phosphokinase (CPK 5885 U/L). Urine toxicology screening solely revealed cocaine. A clinical diagnosis of cocaine toxicity was made and patient was admitted to the intensive care unit because of multi organ failure. Despite downward trending of liver enzymes during the hospital course, he continued to have residual renal insufficiency and a low platelet count at the time of discharge. In a patient with history of recent cocaine use presenting with these manifestations, cocaine itself should be considered as a likely cause.
Rhabdomyolysis is caused by the breakdown and necrosis of muscle tissue and the release of intracellular content into the blood stream. There are multiple and diverse causes of rhabdomyolysis but central to the pathophysiology is the destruction of the sarcolemmal membrane and release of intracellular components into the systemic circulation. The clinical presentation may vary, ranging from an asymptomatic increase in serum levels of enzymes released from damaged muscles to worrisome conditions such as volume depletion, metabolic and electrolyte abnormalities, and acute kidney injury (AKI). The diagnosis is confirmed when the serum creatine kinase (CK) level is > 1000 U/L or at least 5x the upper limit of normal. Other important tests to request include serum myoglobin, urinalysis (to check for myoglobinuria), and a full metabolic panel including serum creatinine and electrolytes. Prompt recognition of rhabdomyolysis is important in order to allow for timely and appropriate treatment. A McMahon score, calculated on admission, of 6 or greater is predictive of AKI requiring renal replacement therapy. Treatment of the underlying cause of the muscle insult is the first component of rhabdomyolysis management. Early and aggressive fluid replacement using crystalloid solution is the cornerstone for preventing and treating AKI due to rhabdomyolysis. Electrolyte imbalances must be treated with standard medical management. There is, however, no established benefit of using mannitol or giving bicarbonate infusion. In general, the prognosis of rhabdomyolysis is excellent when treated early and aggressively.
Background/aims:
Many potentially toxic molecules accumulate in the blood during hepatic dysfunction. In clinical practice, it is very difficult to remove bilirubin, the most widely studied toxin, and particularly the unconjugated form, strongly albumin-bound. The aim of this in vitro study was to assess irreversible bilirubin adsorption as a protein-bound compound marker, using Cytosorb® (Cytosorbents Corp.), a new hemoadsorption device designed to remove cytokines.
Methods:
We performed 4 in vitro experiments, dynamic and static, with different albumin-bilirubin solutions.
Results:
All experiments showed the resin's ability to break the albumin-bilirubin complex (Experiment 1, 2), leading to efficient bilirubin removal for 24 h (Removal Rate: 90% Experiment 3) with minimal albumin loss. No sign of bilirubin release from the charged resin was detected (Experiment 4).
Conclusion:
Cytosorb® seems a promising artificial liver support, thanks to its ability to adsorb bilirubin and its proven ability to modulate the cytokines involved in hepatic dysfunction.
Background: Wheezing has been reported by 32% of habitual smokers of crack cocaine, and several cases of crack-related acute exacerbations of asthma have been reported.
Study objective: To compare the acute effects of physiologically active doses of smoked cocaine base and IV cocaine hydrochloride (HCl), a subphysiologic dose of cocaine base (smoked "placebo"), and IV saline solution placebo on bronchomotor tone, subjective level of intoxication, and cardiovascular responses in healthy habitual crack users.
Design: A single-blind crossover study in which the order of route of administration (inhaled vs IV) was random but placebo always preceded the active drug.
Subjects: Fourteen healthy, nonasthmatic current crack-smoking subjects, 34 to 48 years of age, with a history of previous IV cocaine use (1 to 12 times per lifetime).
Methods: Heart rate, BP, self-rated level of intoxication (scale of 0 to 10), and measurements of airway resistance (Raw) and specific airway conductance (SGaw) were recorded during separate sessions before and 3 to 5, 10, 15, and 30 min after administration of smoked cocaine base (38.5±2.3 [SEM] mg), smoked placebo (2.3±0.9 mg cocaine base), IV cocaine HCl (30.0±2.0 mg), and IV placebo (saline solution).
Results: Both smoked active cocaine and IV cocaine HCl caused comparable, significant (p<0.05) peak levels of acute intoxication (6.7±0.7 and 7.3±0.8, respectively) and increases in heart rate from baseline (29.6±2.9% and 21.4±3.7%, respectively, at 5 min). However, only smoked active cocaine caused significant decreases from baseline in SGaw (25.4±6.3% at 5 min), in contrast to nonsignificant changes after IV cocaine HCl (5.6±7.0% increase) and smoked placebo (10.2±6.0% decrease).
Conclusions: Smoked cocaine base, but not systemically administered cocaine HCl, causes acute bronchoconstriction that is probably mediated by local airway irritation and could account for reports of crack-induced wheezing and asthma attacks in nonasthmatic and asthmatic individuals, respectively.
Cocaine, a natural alkaloid derived from the coca plant, is one of the most commonly abused illicit drugs. Cocaine is commonly abused by inhalation, nasal insufflation, and intravenous injection, resulting in many adverse effects that ensue from local anesthetic, vasoconstrictive, sympathomimetic, psychoactive, and prothrombotic mechanisms. Cocaine can affect all body systems and the clinical presentation may primarily result from organ toxicity. Among the most severe complications are seizures, hemorrhagic and ischemic strokes, myocardial infarction, aortic dissection, rhabdomyolysis, mesenteric ischemia, acute renal injury and multiple organ failure.
The amount of positive cocaine results in an urban emergency department are staggering. The ages of use are becoming more common in older age groups. Most of these patients have underlying medical conditions, including end-stage renal disease (on hemodialysis) and heart and lung disease. Most of their visits to the emergency department are for cocaine exacerbation of underlying chronic condition, adding exponentially to health care dollars. This article describes the history and pharmacology of illicit cocaine use.
Hepatotoxicity due to cocaine has been well described in animal models. There are few reports on cocaine-induced hepatic injury in humans; however, its link to rhabdomyolysis and renal failure is better known. We report a case of reversible acute hepatonephrotoxicity associated with recreational cocaine use. The proposed mechanisms responsible for its hepatic and renal toxicity are reviewed.
Intranasal cocaine is used frequently as a local anesthetic during many rhinolaryngologic procedures. Although its "recreational" use in high doses has been associated with chest pain and myocardial infarction, this association has not been established when cocaine is used in low doses as a topical anesthetic, and its effect on the coronary vasculature of humans is unknown. We studied the effects of intranasal cocaine (10 percent cocaine hydrochloride; 2 mg per kilogram of body weight) on the blood flow in and dimensions of the coronary arteries and on myocardial oxygen demand in 45 patients (34 men and 11 women, 36 to 67 years of age) who were undergoing cardiac catheterization for the evaluation of chest pain. Heart rate, arterial pressure, blood flow in the coronary sinus (measured by thermodilution), and the dimensions of the epicardial left coronary artery (measured by quantitative arteriography) were measured before and 15 minutes after the intranasal administration of saline (in 16 patients) or cocaine (in 29). No variables changed after the administration of saline. After cocaine was administered, the heart rate and arterial pressure rose, the coronary-sinus blood flow fell (from a mean [+/- SD] of 149 +/- 59 ml per minute to 124 +/- 53 ml per minute), and the diameter of the left coronary artery decreased by 8 to 12 percent (P less than 0.01 for all comparisons). No patient had chest pain or electrocardiographic evidence of myocardial ischemia after the administration of cocaine. Subsequently, the administration of the alpha-adrenergic blocking agent phentolamine caused all these values to return to base-line levels. There was no difference in response between the patients found to have disease of the left coronary artery (n = 28) and those without such disease (n = 17). We conclude that the intranasal administration of cocaine near the dose used for topical anesthesia causes vasoconstriction of the coronary arteries, with a decrease in the coronary blood flow, despite an increase in myocardial oxygen demand, and that these effects are mediated by alpha-adrenergic stimulation. It is reasonable to assume that these effects would be more pronounced at the much higher doses associated with the recreational use of cocaine.
Intracerebral microdialysis was used to assess the effects of cocaine-HCl on extracellular concentrations of the excitatory amino acids aspartate and glutamate in the nucleus accumbens of awake, freely moving rats. After an initial equilibration period, cocaine (7.5, 15 or 30 mg/kg) or saline was injected i.p., and samples were collected for an additional 2 h. The highest dose of cocaine (30 mg/kg, i.p.) caused a 4-fold increase in glutamate levels and an 18-fold increase in aspartate levels over baseline. To verify that the source of the extracellular aspartate and glutamate was neuronal, additional experiments were conducted using Ca(2+)-free microdialysis buffer, and buffer containing 10 microM tetrodotoxin. Local perfusion with Ca(2+)-free buffer reduced the increase of extracellular aspartate and glutamate in rats injected with 30 mg/kg cocaine. Tetrodotoxin significantly decreased the cocaine-induced increase in excitatory amino acids, but not the behavioral response.
Cocaine ingestion has been associated with thrombosis of coronary as well as peripheral arteries, but the mechanism by which cocaine promotes thrombus formation is unknown. Accordingly, we determined whether cocaine activates human platelets by flow cytometric analysis of whole blood to which cocaine was added.
Activated platelets were detected by "two-color" flow cytometric analysis of the binding of fluorescently labeled antibodies directed against either platelet-associated fibrinogen or P-selectin, which are found on the surface of platelets only after stimulation. Platelets were distinguished from other constituents of whole blood by their ability to bind an anti-glycoprotein Ib antibody bound to both activated and resting platelets. Incubation of whole blood with cocaine, in concentrations of 10 microM to 13 mM, induced significant increases in both platelet-associated fibrinogen (range of increase, 45 +/- 12% to 125 +/- 40%) and P-selectin expression (36 +/- 15% to 112 +/- 24%). In platelets suspended in either buffer or plasma, however, P-selectin expression was detected only at the highest cocaine concentration (85 +/- 13% increase in plasma and 59 +/- 7% in buffer). Neither aspirin nor the ADP scavenger apyrase inhibited cocaine-induced P-selectin expression. Cocaine inhibited the uptake of 14C-radiolabeled serotonin by platelets (IC50, 8.7 microM). P-selectin expression and fibrinogen binding were found after the addition of cocaine alone to blood taken from some but not all donors; however, platelet activation in response to submaximal concentrations of the agonists ADP or epinephrine was enhanced by a low concentration of cocaine added to blood from every donor.
Cocaine, in concentrations similar to those found clinically, induces activation of individual platelets studied in whole blood from some but not all donors, and platelet response to physiological agonists is enhanced by cocaine. Thus, cocaine-induced platelet activation may contribute to thrombosis following cocaine ingestion.
Since patients with cocaine overdose were reported to develop rhabdomyolysis involving skeletal muscle damage leading to elevated levels of serum creatine kinase (CK), we determined whether cocaine can directly act on isolated rat skeletal muscles and increase the leakage of CK. In the fast-twitch muscle such as the extensor digitorum longus (EDL), following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 0.6, 0.7, 0.9, and 1.2 units/mg of muscle respectively. On exposure of EDL to 0.1, 0.5, and 1.0 mM cocaine, there was no significant change in CK leakage. In the slow-twitch muscle such as the soleus, following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 1.5, 2.2, 2.7, and 3.1 units/mg, which was significantly greater (P < 0.001) than in EDL at each time interval. On exposure of soleus to 0.1 mM cocaine, the CK leakage did not increase significantly, but on exposure to 0.5 mM cocaine, it significantly increased to 2.4, 3.4, 4.4, and 5.7 units/mg, and on exposure to 1.0 mM cocaine, it further increased to 2.7, 4.9, 6.5, and 7.6 units/mg. The CK activity of fresh muscle homogenate was 115.5 units/mg in EDL and 51.9 units/mg in soleus. These results indicate that cocaine can directly act on skeletal muscle and increase the leakage of CK especially from slow-twitch muscle like soleus, but not from fast-twitch muscle like EDL.
This is a report of 50 consecutive patients with juxtapyloric perforations after smoking "crack" cocaine (cocaine base) at one urban public hospital.
Although the exact causal relation between smoking crack cocaine and a subsequent juxtapyloric perforation has not been defined, surgical services in urban public hospitals now treat significant numbers of male addicts with such perforations. This report describes the patient set, presentation, and surgical management and suggests a possible role for Helicobacter pylori in contributing to these perforations.
A retrospective chart review was performed, supplemented by data from the patient log in the department of surgery.
From 1994 to 1998, 50 consecutive patients (48 men, 2 women) with a mean age of 37 had epigastric pain and signs of peritonitis a median of 2 to 4 hours (but up to 48 hours) after smoking crack cocaine. A history of chronic smoking of crack as well as chronic alcohol abuse was noted in all patients; four had a prior history of presumed ulcer disease in the upper gastrointestinal tract. Free air was present on an upright abdominal x-ray in 84% of patients, and all underwent operative management. A 3- to 5-mm juxtapyloric perforation, usually in the prepyloric area, was found in all patients. Omental patch closure was used in 49 patients and falciform ligament closure in 1. Two patients underwent parietal cell vagotomy as well. In the later period of the review, antral mucosal biopsies were performed through the juxtapyloric perforation in five patients. Urease testing was positive for infection with H. pyonri in four, and these patients were prescribed appropriate antimicrobial drugs.
Juxtapyloric perforations after the smoking of crack cocaine occur in a largely male population of drug addicts who are 8 to 10 years younger than the patient group that historically has perforations in the pyloroduodenal area. These perforations are usually 3 to 5 mm in diameter, and an antral mucosal biopsy for subsequent urease testing should be performed if the location and size of the ulcer allow this to be done safely. Omental patch closure is appropriate therapy for patients without a history of prior ulcer disease; antimicrobial therapy and omeprazole are prescribed when H. pylori is present.
Cocaine abuse has reached epidemic proportions in the United States, and several forms of renal disease have been associated with this widespread use. The hemodynamic actions of cocaine, as well as its effects on matrix synthesis, glomerular inflammation, and glomerulosclerosis, may contribute to renal injury. Cocaine abuse has been associated with various forms of acute renal failure and acid-base and/or electrolyte disorders and may also have a role in the progression of chronic renal failure to end-stage renal disease. In utero exposure to cocaine has been associated with urogenital tract anomalies. Medical management of a hypertensive emergency caused by acute cocaine toxicity requires a multisystem approach, with close monitoring of cardiac, neurological, and renal functions.
Cocaine use can result in various gastrointestinal complications, including gastric ulcerations, retroperitoneal fibrosis, visceral infarction, intestinal ischemia, and gastrointestinal tract perforation. We report cocaine-associated colonic ischemia in three patients and review the literature. Including ours, 28 cases have been reported, with a mean patient age of 32.6 years (range, 23 to 47 years); 53.5% were men and 46.5% were women. The interval between drug ingestion and onset of symptoms varied from 1 hour to 2 days. Cocaine is a potentially life-threatening cause of ischemic colitis and should be included in the differential diagnosis of any young adult or middle-aged patient with abdominal pain and bloody diarrhea, especially in the absence of estrogen use or systemic disorders that can cause thromboembolic events, such as atrial fibrillation.
The lethal effects of cocaine are unique among those of other illicit drugs because cocaine has the propensity to cause hyperthermia. The traditional view is that cocaine causes a hypermetabolic state with increased heat production. However, because cocaine-induced hyperthermia occurs primarily in hot weather, it is hypothesized that cocaine also impairs thermoregulatory adjustments that mediate heat dissipation.
To test the effects of cocaine on body temperature regulation in humans.
Randomized, double-blind, placebo-controlled crossover trial.
A cardiovascular physiology laboratory in Dallas, Texas.
7 healthy, cocaine-naive volunteers.
Progressive passive heat stress, during which each participant received intranasal cocaine (2 mg/kg of body weight) or placebo (lidocaine, 2 mg/kg).
Esophageal temperature, skin blood flow, sweat rate, and perceived thermal sensation.
Three major new findings were noted. First, cocaine substantially augmented the progressive increase in esophageal temperature during heat stress (P < 0.001). Second, this augmentation was explained by a rightward shift in the esophageal temperature threshold for the onset of both cutaneous vasodilation (37.37 +/- 0.09 degrees C for cocaine vs. 37.06 +/- 0.07 degrees C for lidocaine; P = 0.01) and sweating (37.38 +/- 0.09 degrees C for cocaine vs. 37.07 +/- 0.06 degrees C for lidocaine; P = 0.002). Third, cocaine paradoxically impaired the perception of heating by attenuating the progressive increase in thermal discomfort associated with heat stress.
In humans, impaired heat dissipation is a major mechanism by which cocaine elevates body temperature. When healthy, cocaine-naive persons are subjected to passive heating, pretreatment with even a small dose of intranasal cocaine impairs sweating and cutaneous vasodilation (the major autonomic adjustments to thermal stress) and heat perception (the key trigger for behavioral adjustments).
European Monitoring Centre for Drugs and Drug Addiction
- European Drug Report