Rhabdomyolysis in a patient treated with colchicine and atorvastatin

OBJECTIVE: To report a case of severe rhabdomyolysis that developed after administration of atorvastatin to a patient receiving regular colchicine treatment. CASE SUMMARY: A 45-year-old man with nephrotic syndrome and amyloidosis presented with dyspnea, altered mentation, and severe fatigue. He had been taking colchicine 1.5 mg/day for amyloidosis for 3 years without adverse effects. Atorvastatin 10 mg/day was prescribed for hypercholesterolemia one month prior to admission. After 2 weeks of atorvastatin treatment, he began to experience myalgia and reduced muscle strength. The creatinine and creatine kinase concentrations on admission were 8.1 mg/dL and 9035 U/L, respectively. The patient was diagnosed with rhabdomyolysis with the findings of myoglobinuric, oliguric acute renal failure, and more than 50-fold elevated creatine kinase concentration. His muscle strength improved after withdrawal of atorvastatin and colchicine. However, he died because of nosocomial pneumonia that developed during his hospital stay. The Naranjo probability scale indicated that atorvastatin and colchicine were probable causes of rhabdomyolysis. DISCUSSION: Atorvastatin and colchicine have well-known myotoxic adverse effects. Despite atorvastatin's proven safety, its use with certain drugs, such as colchicine, makes it a potential myotoxic drug. This might be because concomitant administration of P-glycoprotein substrates, such as statins, and colchicine, which is a P-glycoprotein inhibitor, modifies pharmacokinetics by increasing bioavailability and organ uptake of the substrates, leading to more adverse reactions and toxicities. CONCLUSIONS: We recommend checking the creatine kinase level one week after prescribing 2 or more potentially myotoxic drugs concomitantly, after dose increase of a myotoxic drug, or after prescribing a new drug to a patient already using other myotoxic agents.     

Rhabdomyolysis and acute renal failure following an ethanol and diphenhydramine overdose

OBJECTIVE: To report a case of nontraumatic rhabdomyolysis complicated by oliguric, acute renal failure following an intentional overdose of ethanol and diphenhydramine. CASE SUMMARY: A 21-year-old white man was admitted through the emergency department following an intentional overdose of ethanol and diphenhydramine. The patient subsequently developed acute renal failure, and a diagnosis of nontraumatic rhabdomyolysis was made. With the absence of other common causes in this case, the rhabdomyolysis was believed to be due to the combined ethanol and diphenhydramine overdose. DISCUSSION: Rhabdomyolysis is a severe and life-threatening syndrome caused by various insults to skeletal muscle, including drug-induced injury. Early detection and institution of effective treatments are essential to minimizing the complications of this syndrome. A delay in establishing the diagnosis in this case likely contributed to the severity of the renal failure. CONCLUSIONS: Nontraumatic rhabdomyolysis is an uncommon adverse outcome of drug and toxin ingestion. Due to the potential severity of the complications of this syndrome and the importance of early recognition and treatment to prevent renal failure, clinicians should have a high index of suspicion for rhabdomyolysis following overdoses that involve alcohol or antihistamines.     

Rhabdomyolysis with concurrent atorvastatin and diltiazem

OBJECTIVE: To report a case of rhabdomyolysis and acute hepatitis associated with the coadministration of atorvastatin and diltiazem. CASE SUMMARY: A 60-year-old African American man with a significant past medical history presented to the emergency department with acute renal failure secondary to rhabdomyolysis. In addition, liver enzymes were elevated to greater than 3 times normal. The only change in medication was the initiation of diltiazem 3 weeks earlier for atrial fibrillation to a complicated medication regimen that included atorvastatin. DISCUSSION: Rhabdomyolysis has been reported in patients receiving hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors when coadministered with agents that may inhibit their metabolism. Atorvastatin is the most potent of this class of agents currently available and is commonly used in the treatment of hyperlipidemia. Rhabdomyolysis resulting from the drug interaction between diltiazem and other HMG-CoA reductase inhibitors has been described in the literature. However, no report has specifically associated this adverse event with atorvastatin and diltiazem. We describe a patient with a complex medication regimen who was admitted for rhabdomyolysis and accompanying acute renal failure, along with acute hepatitis, thought to be secondary to a drug interaction between atorvastatin and diltiazem. CONCLUSIONS: While optimizing the patient's lipid profile should be the primary factor in choosing one statin over another, the potential for drug interactions requires close attention. All patients beginning HMG-CoA reductase inhibitor therapy should be counseled regarding the signs and symptoms of muscle injury; particular attention should be paid to those patients who are taking medications that may interact.     

Propofol infusion syndrome: a case of increasing morbidity with traumatic brain injury.

A previously healthy 16-year-old boy with a closed, severe traumatic brain injury was admitted to a surgical and trauma intensive care unit. He was given a continuous infusion of propofol for sedation and to control intracranial pressure. About 3 days after the propofol infusion was started, metabolic acidosis and rhabdomyolysis developed. Acute renal failure ensued as a result of the rhabdomyolysis. Tachycardia with wide QRS complexes developed without hyperkalemia. The patient died of refractory cardiac dysrhythmia and circulatory collapse approximately 36 hours after the first signs of propofol infusion syndrome appeared. Propofol infusion syndrome is a rare but frequently fatal complication in critically ill children who are given prolonged high-dose infusions of the drug. The syndrome is characterized by severe metabolic acidosis, rhabdomyolysis, acute renal failure, refractory myocardial failure, and hyperlipidemia. Despite several publications on the subject in the past decade, most cases still seem to remain undetectable.     

The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome

Propofol infusion syndrome (PRIS) is a rare and often fatal syndrome described in critically ill children undergoing long-term propofol infusion at high doses. Recently several cases have been reported in adults, too. The main features of the syndrome consist of cardiac failure, rhabdomyolysis, severe metabolic acidosis and renal failure. To date 21 paediatric cases and 14 adult cases have been described. These latter were mostly patients with acute neurological illnesses or acute inflammatory diseases complicated by severe infections or even sepsis, and receiving catecholamines and/or steroids in addition to propofol. Central nervous system activation with production of catecholamines and glucocorticoids, and systemic inflammation with cytokine production are priming factors for cardiac and peripheral muscle dysfunction. High-dose propofol, but also supportive treatments with catecholamines and corticosteroids, act as triggering factors. At the subcellular level, propofol impairs free fatty acid utilisation and mitochondrial activity. Imbalance between energy demand and utilisation is a key pathogenetic mechanism, which may lead to cardiac and peripheral muscle necrosis.Propofol infusion syndrome is multifactorial, and propofol, particularly when combined with catecholamines and/or steroids, acts as a triggering factor. The syndrome can be lethal and we suggest caution when using prolonged (>48 h) propofol sedation at doses higher than 5 mg/kg per h, particularly in patients with acute neurological or inflammatory illnesses. In these cases, alternative sedative agents should be considered. If unsuitable, strict monitoring of signs of myocytolysis is advisable.     

Massive acetaminophen ingestion with early metabolic acidosis and coma: treatment with IV NAC and continuous venovenous hemodiafiltration

Context.?We report the extraction of acetaminophen by continuous venovenous hemodiafiltration (CVVHD) during treatment of an acute ingestion of 200 g with a peak recorded serum acetaminophen level of 1,614 mg/L (10,652 μmol/L).?Case details.?The patient presented with early onset of coma, metabolic acidosis, and hypotension in the absence of significant hepatic injury. In addition to N-acetylcysteine (NAC) therapy, CVVHD was performed to manage the acid–base disturbance. Flow rate, effluent volume, and serum and effluent drug concentrations were obtained at hourly intervals. During 16 h of CVVHD the acetaminophen level dropped from 1,212 to 247 mg/L.?Discussion.?The average clearance of acetaminophen by CVVHD was 2.53 L/h, with removal of 24 g of acetaminophen over 16 h. As NAC is effective in preventing hepatic injury after acute acetaminophen overdose, the role of dialysis or CVVHD is limited.     

Injecting other users: A pilot study in an area of high prevalence of drug-related deaths

Background:?It has been suggested that some intravenous drug user deaths may occur in the context of receiving injections from other people.?Aim:?To investigate the nature, reasons, risks, and circumstances of the practice of injecting other drug users.?Method:?Questionnaire data collected over 30 weeks from injecting drug users involved with the Brighton and Hove City Substance Misuse Service.?Results:?The prevalence of these practices (the giving or receiving of injections) was estimated as 26%. “Problems with injecting technique” was the commonest reason given for engaging in these practices and sharing injecting equipment was common. The practice most commonly occurred between friends and partners. Responders to the study perceived these practices as being no different or less safe than self-injecting with regard to the risk of overdose.?Conclusions:?Injecting other users may be a common practice and was perceived by study respondents as being no different or less safe than self-injecting with regard to the risk of overdose. This pilot study would benefit from further replication.     

Electrocardiographic effects of methylphenidate overdose

Objectives.?Stimulants used in the management of attention-deficit hyperactivity disorder have been associated with an increased risk of sudden cardiac death. One mechanism could involve drug-induced repolarization delay, reflected as prolongation of the QT interval on the electrocardiogram, which has been described in some recipients of methylphenidate in therapeutic doses. Because QT prolongation is usually dose-related, this study was performed to investigate effects of methylphenidate overdose on the QT interval.?Methods.?Adults with methylphenidate overdose identified retrospectively were matched for sex and heart rate with a control subject with overdose of a noncardiotoxic substance, mainly acetaminophen. Notes were reviewed for clinical details and coingestants. Admission 12-lead electrocardiograms were individually calibrated and analyzed using a manual digitizer in a blinded manner by a single investigator. Mean QRS and QT intervals were calculated and differences between groups were analyzed.?Results.?Twenty-three cases of methylphenidate overdose (median reported dose 120 mg, range 40–1,500 mg) were identified (10 males, 13 females, mean age 27.8 years). There were multiple coingestants. Level of consciousness and mean hemodynamic variables were within normal limits for all cases. Symptoms recorded in cases included anxiety (32%), dilated pupils (20%), abdominal pain (16%), vomiting (12%), palpitations (12%), and chest pain (8%). No arrhythmias were recorded. Mean heart rate was 92.4/min in methylphenidate cases and 93.8/min in the heart rate-matched controls. There were no significant differences between the groups in mean QRS (cases 86.1, controls 86.2, mean difference 0.1, 95% confidence interval = ?5.1 to 5.0 ms) or mean QT intervals (cases 354, controls 355, mean difference ?0.8, 95% confidence interval = ?10.7 to 9.2 ms).?Conclusions.?Methylphenidate overdose is unlikely to have substantial effects on the QRS or QT intervals.     

Propofol infusion syndrome in critically ill patients

OBJECTIVE: To describe the clinical presentation of propofol infusion syndrome in critically ill adults. DATA SOURCES: Clinical literature was accessed through MEDLINE (1966 - March 2001). Key search terms included Diprivan, propofol, and propofol infusion syndrome. Case reports and small case series evaluating the use and toxicity of propofol in sedating critically ill adults were reviewed. DATA SYNTHESIS: The association between propofol infusion syndrome and death in children secondary to myocardial failure is well documented. However, few data are available regarding the syndrome in critically ill adults. Based on a review of those data, it appears that propofol infusion syndrome can occur in both children and adults. Common clinical features of propofol infusion syndrome may include hyperkalemia, hepatomegaly, lipemia, metabolic acidosis, myocardial failure, and rhabdomyolysis. Although the premise has not been proven, recent published cases appear to demonstrate an association between propofol infusion and death secondary to myocardial failure. CONCLUSIONS: Until further safety data become available, caution should be exercised when using high-dose (>5 mg/kg/h) and long-term (>48 h) propofol infusion in sedating critically ill adults.     

Guanfacine overdose resulting in initial hypertension and subsequent delayed,persistent orthostatic hypotension

Introduction. Guanfacine is an α₂-adrenoreceptor agonist used for the treatment of attention-deficit hyperactivity disorder and tic disorders. Few reports exist regarding overdose with guanfacine.?Case Report. A 16-year-old female with Tourette's syndrome presented with diaphoresis, dry mouth, and hypertension 8 h after ingesting 25 mg of guanfacine. These symptoms improved and her blood pressure (BP) normalized over 2 h. Thirty hours following ingestion, she experienced near syncope and returned to the emergency department. She was noted to have orthostatic hypotension and a prolonged QTc interval of 593 ms on electrocardiogram. With only fluid support, she was asymptomatic by 60 h postingestion and her QTc interval had improved to 511 ms.?Discussion. This experience suggests a much delayed onset of symptoms may occur and that the QTc interval may be prolonged, necessitating a longer period of monitoring in a patient presenting with an overdose.     

Club drugs: MDMA, gamma-hydroxybutyrate (GHB), Rohypnol, and ketamine

Club drugs are substances commonly used at nightclubs, music festivals, raves, and dance parties to enhance social intimacy and sensory stimulation. The most widely used club drugs are 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy; gamma-hydroxybutyrate (GHB); flunitrazepam (Rohypnol); and ketamine (Ketalar). These drugs are popular because of their low cost and convenient distribution as small pills, powders, or liquids. Club drugs usually are taken orally and may be taken in combination with each other, with alcohol, or with other drugs. Club drugs often are adulterated or misrepresented. Any club drug overdose should therefore be suspected as polydrug use with the actual substance and dose unknown. Persons who have adverse reactions to these club drugs are likely to consult a family physician. Toxicologic screening generally is not available for club drugs. The primary management is supportive care, with symptomatic control of excess central nervous system stimulation or depression. There are no specific antidotes except for flunitrazepam, a benzodiazepine that responds to flumazenil. Special care must be taken for immediate control of hyperthermia, hypertension, rhabdomyolysis, and serotonin syndrome. Severe drug reactions can occur even with a small dose and may require critical care. Club drug over-dose usually resolves with full recovery within seven hours. Education of the patient and family is essential.     

Fatal poisoning in children: Acute Colchicine intoxication and new treatment approaches

Background. Colchicine poisoning is potentially life-threatening. Deaths generally result from hypovolemic shock and cardiovascular collapse or secondary to rapidly progressive multiorgan failure. Objective. The purpose of this study is to discuss the clinical effects, treatments and outcomes of pediatric colchicine poisoning and highlight the possible benefits of urgent plasma and whole blood exchange therapy for those patients who were believed to ingest potentially lethal doses of the drug. Methods. Current study was designed as an observational case series study. The medical records of children aged 0–16 years who were hospitalized for colchicine poisoning at the Pediatric Intensive Care Unit of, between November 1985 and March 2011 were retrospectively evaluated. Results. We present twenty-three children with colchicine poisoning. Nausea and vomiting were the most common presenting complaint, in 70% of patients. Sixteen of the 23 cases presented after ingesting sub-toxic doses of colchicine (< 0.5 mg/kg), whereas 3 patients had consumed toxic doses of the drug (0.5–0.8 mg/kg). The remaining 4 patients were hospitalized after taking colchicine at a lethal dose (> 0.8 mg/kg). Three patients (13%) died. Conclusions. Any patient suspected of ingesting high doses of colchicine should prompt immediate fluid and electrolyte resuscitation and invasive hemodynamic monitorization in a pediatric intensive care unit. Although there is lack of strong evidence, early initiation of either whole blood or plasma exchange may be considered in patients presenting with lethal-dose colchicine intoxication. These reported experience of us put forth further research for consideration.     

Bupropion toxicokinetic: A case report

Context.?The toxicokinetics of sustained-release bupropion are not well described.?Case.?A 23-year-old Caucasian male took an overdose of 5,700 mg of sustained release bupropion with no co-ingestant. Venous serum samples were assayed for bupropion concentrations over the next 5 days. The peak concentration was 1.114 mg/L. The observed T_max was found to be 8.25 h, the calculated alpha half-life 10.9 h (±SE of 4.47%), and the calculated beta half-life 19.8 h (±SE 12.62%). The alpha half-life and T_max differ significantly from those seen in therapeutic doses.?Discussion.?Bezoar formation may underlie these differences. Interventions which reduce the absorption of sustained release bupropion may be effective in overdose.     

Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose

Objective.?Diphenhydramine is an H1 histamine antagonist that is commonly used for allergic reactions, colds and cough, and as a sleep aid. In addition to anticholinergic and antihistaminergic effects, sodium channel blockade becomes evident following diphenhydramine overdose. While seizures may occur following overdose of a diphenhydramine, status epilepticus is distinctly uncommon. We report a case with both status epilepticus and wide-complex dysrhythmias following an intentional diphenhydramine overdose. Case report.?A 36-year-old woman with a medical history of hypothyroidism on levothyroxine was brought to the emergency department with active seizures by emergency medical services after what was later determined to be a diphenhydramine overdose. One hour after an argument with her husband he found her lethargic in a locked room. Initial vital signs were: blood pressure, 90/55?mmHg; heart rate, 160 beats/min; respiratory rate 18 breaths/min; room air oxygen saturation, 99%; temperature, 99.8°F; rapid point-of-care glucose, 130?mg/dL. The generalized seizures continued for duration of 30?min, despite the intravenous administration of 8?mg of lorazepam. The patient underwent endotracheal intubation and a propofol infusion terminated her seizures. An electrocardiogram after the status was terminated which revealed a wide-complex tachycardia with QRS duration of 127?ms. The QRS narrowed after 200?mEq of intravenous sodium bicarbonate was administrated. The patient was neurologically intact upon extubation on hospital day 2. The serum diphenhydramine concentration drawn on arrival to the ED was 1200?ng/mL (9–120?ng/mL); a tricyclic screen was negative. Discussion.?While seizures and sodium channel blockade are recognized complications of diphenhydramine toxicity, reported cases of status epilepticus from diphenhydramine overdose are rare. Elements of the patient's presentation were similar to a tricyclic overdose and management required aggressive control of her seizures, sodium bicarbonate therapy, and recognizing that physostigmine was contraindicated due to wide complex tachycardia. Conclusions.?Diphenhydramine overdose may cause status epilepticus and wide-complex tachycardia. Management should focus on antidotal therapy with sodium bicarbonate and supportive neurological management with appropriate anticonvulsants and airway protection if clinically indicated.     

Colchicine poisoning: the dark side of an ancient drug

Introduction. Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians. Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome. Methods. We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included “colchicine” and “poisoning” or “overdose” or “toxicity” or “intoxication.” Toxicokinetics. Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements. Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys. Therapeutic and toxic doses. The usual adult oral doses for FMF is 1.2–2.4 mg/day; in acute gout 1.2 mg/day and for gout prophylaxis 0.5–0.6 mg/day three to four times a week. High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7–26 mg. Drug interactions. CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy. Mechanisms of toxicity. Colchicine's toxicity is an extension of its mechanism of action – binding to tubulin and disrupting the microtubular network. As a result, affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility. The culmination of these mechanisms leads to multi-organ dysfunction and failure. Reproductive toxicology and lactation. Colchicine was not shown to adversely affect reproductive potential in males or females. It crosses the placenta but there is no evidence of fetal toxicity. Colchicine is excreted into breast milk and considered compatible with lactation. Clinical features. Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10–24 h after ingestion – gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after ingestion – multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis. Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness. Diagnosis. History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis. Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia). Management. Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent (<60 min) ingestions may warrant gastric lavage. Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment. Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available. Conclusion. Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed.     

CC4-03: The Use of Administrative Data and Natural Language Processing to Estimate the Incidence of Statin-related Rhabdomyolysis

Background/Aims Despite the problem of misclassification, many studies of adverse drug reactions (ADRs) rely on administrative data rather than events validated by medical record review. We evaluated the new ICD-9 code for rhabdomyolysis (728.88) and natural language processing (NLP) as methods to identify cases of statin-related rhabdomyolysis, and estimated the incidence with various statins and doses. Methods We conducted a population-based study of statin users in Group Health Cooperative from 2006-2010. Person-years of statin use among all enrollees by statin and dose were estimated using computerized pharmacy records. Trained abstractors reviewed the medical records of selected statin users to identify cases of statin-related rhabdomyolysis and myopathy, defined as muscle injury with a peak creatine kinase level = 10x and 5-10x the upper limit of normal, in the absence of other likely etiologies. Results Review of medical records for 361 statin users with a qualifying administrative code yielded 24 cases of statin-related rhabdomyolysis and 12 of myopathy. The positive predictive value of the rhabdomyolysis ICD-9 code was only 7.5% (22/292). NLP methods identified another 5 cases of rhabdomyolysis and 6 of myopathy. Using validated cases, the rhabdomyolysis incidence rate (IR) per 100,000 person-years of statin use was 13.2 for simvastatin compared with 5.2 for users of other statins (IRR 2.61; 95% CI, 1.03-7.84), and 64.8 for the 80 mg/day dose of simvastatin compared with 5.3 for the 20 mg/day dose (IRR 12.2; 95% CI, 3.6-52.3). In an analysis using only the ICD-9 code for rhabdomyolysis, the IRR for simvastatin compared with other statins was 1.03 (95% CI 0.80-1.34), and for 80 mg/day dose of simvastatin compared with 20 mg/day it was 1.77 (95% CI 1.05-2.88). Discussion Use of the administrative diagnostic code for rhabdomyolysis was highly nonspecific for this ADR and resulted in weaker associations than methods that verified ADRs with medical record review. The use of administrative data alone in surveillance studies of other medication ADRs with multiples causes, such as drug-induced liver injury, may fail to detect actionable and clinically important harms.     

Fab fragments of ovine antibody to colchicine enhance its clearance in the rat

Abstract

Context. Colchicine is an anti-inflammatory alkaloid used for the treatment of acute gout, but has a narrow therapeutic index. Colchicine overdoses are relatively rare, but have high mortality requiring rapid treatment. Objective. To evaluate the ability of a newly available ovine fragment antigen-binding (Fab) antibody to colchicine (ColchiFab^?) to protect rats against renal and other injury 24 h after colchicine ingestion. Materials and methods. Rats were gavaged with colchicine (5 mg/kg), then 2 h later injected intraperitoneally with 5 ml of sterile saline, or Fab anti-colchicine, a newly available ovine antibody to colchicine. Samples of blood were taken at 1, 2, 5 and 24 h after gavage, and urine was collected from 5 to 24 h after gavage. Concentrations of colchicine in tissue, blood and urine were measured by liquid chromatography/mass spectrometry, concentrations of Fab anti-colchicine, urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 or KIM-1 by enzyme-linked immunosorbent assay or ELISA, while concentrations of creatine kinase and creatinine (Cr) were measured enzymatically. Results. Colchicine equilibrated rapidly throughout the body and increased serum creatine kinase. Fab anti-colchicine also rapidly redistributed to the blood and remained at high concentrations over 24 h. Fab anti-colchicine caused a rapid 7.1-fold increase in serum colchicine level, followed by excretion of both colchicine and Fab anti-colchicine through the urine. This was associated with the accumulation of colchicine in the kidney, a reversal of colchicine-induced diarrhoea, and increasing urinary NGAL level; from 168 ± 48 to 477 ± 255 ng/mmol Cr [mean ± standard deviation or SD]. Discussion. Fab anti-colchicine greatly increased the clearance of colchicine, although increasing NGAL level suggested the presence of mild kidney damage. Conclusion. These data suggest clinical utility for Fab anti-colchicine in the treatment of colchicine overdose.     

The use of propofol sedation in a paediatric intensive care unit

Background: The aim of this study was to prospectively evaluate and report the experience of the use of continuous intravenous propofol sedation in a paediatric intensive care unit (PICU). Methods: All children younger than 16 years who were admitted to the PICU at a University Hospital for slightly more than a year and received propofol infusion were included prospectively and data were recorded before and within 6 h after completion of the propofol infusion. Results: A total of 174 out of 955 children (18·2%) received propofol infusion for sedation. The median age was 2 years 10 months (range: 2 months to 16 years), duration of propofol infusion 13 h (range: 1·6–179 h) and dose of propofol 2·9 mg/kg/h (range: 0·3–6·5 mg/kg/h). No one developed signs of the propofol infusion syndrome (PRIS). Neither dose >3 mg/kg/h, duration of infusion >48 h nor both were found to be related to adverse metabolic derangements or circulatory failure. Eight children increased their lactate concentration ≥1·8 mmol/L during propofol infusion. All had a favourable outcome. One child who had received propofol infusion for 10 h died, but this occurred 14 h after the infusion ceased and was without doubt attributed to a multiple organ failure not related to the propofol infusion. Conclusion: Propofol infusion was used in this population at low risk of PRIS with no metabolic or circulatory adverse effects. These findings indicate that the occurrence of adverse effects may not be directly related to dose or duration of infusion, but emphasizes the risk that sporadic factors may be involved, such as genetic mutations. Guidelines are presented.