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Query: UMLS:C0018801 (heart failure)
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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.
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PMID:The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. 1468 64

Propofol is used for the treatment of refractory status epilepticus. When given as a long-term infusion propofol may cause a rare but frequently fatal complication, the propofol infusion syndrome. The hallmarks are metabolic acidosis, lipemia, rhabdomyolysis and myocardial failure. Propofol infusion syndrome is caused by impaired fatty acid oxidation. Beside anticonvulsants the ketogenic diet, a high-fat, low-carbohydrate, adequate-protein diet, is an effective treatment for difficult-to-control seizures. We report a 10-year-old boy with catastrophic epilepsy, who developed fatal propofol infusion syndrome when a ketogenic diet was initiated. Substances like propofol which impair fatty acid oxidation may pose an increased risk if combined with ketogenic diet.
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PMID:Fatal propofol infusion syndrome in association with ketogenic diet. 1532 67

Propofol infusion syndrome has been increasingly recognized as a syndrome of unexplained myocardial failure, metabolic acidosis, and rhabdomyolysis with renal failure. It has been described only with acute neurologic injury or acute inflammatory diseases complicated by severe infections or sepsis. It appears to develop in the context of high-dose, prolonged propofol (100 microg/kg/min) treatment in combination with catecholamines and/or steroids. This was first noted in children but is increasingly recognized in adults. This is a case report of 2 patients (a 42-year-old man and a 17-year-old girl) who had acute renal failure associated with use of propofol in the appropriate clinical setting. It examines the pathophysiology and the possible mechanisms of this condition and illustrates the need to consider it as the cause of rhabdomyolysis and acute renal failure in critically ill patients.
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PMID:Propofol infusion syndrome: an unusual cause of renal failure. 1555 15

In critically ill patients, adequate sedation increases comfort, minimizes stress response and facilitates diagnostic and therapeutic procedures. Propofol (2-, 6-diisopropylphenol) is an intravenous sedative-hypnotic agent popular for sedation in the Intensive Care Unit. The favorable propofol pharmacokinetic, characterized by a three compartment linear model, allows rapid onset and short duration of action. The emergence time from sedation with propofol varies with the depth and the duration of sedation and the patient's bodyweight. Propofol causes hypotension, particularly in volume depleted patients, decreases cerebral oxygen consumption, reduces intracranial pressure and has potent anti-convulsant properties. It is a potent antioxidant, has anti-inflammatory properties and is a bronchodilator. As a consequence of these properties, propofol is being increasingly used in the management of traumatic head injury, status epilepticus, delirium tremens, status asthmaticus and in septic patients. Prolonged use (>48 h) of high doses of propofol (>66 mcg/Kg/min) has been associated with lactic acidosis, bradycardia, and lipidemia in pediatric patients. A rare complication firstly reported in pediatrics patients and also observed in adults is known as "propofol syndrome" characterized by myocardial failure, metabolic acidosis and rhabdomiolysis. Hyperkalemia and renal failure have also been associated with this syndrome. Hypertriglyceridemia and pancreatitis are uncommon complications. A large number of trials have compared the use of propofol with midazolam. Sedation with propofol is associated with adequate sedation in ICU patients, shorter weaning time and earlier tracheal extubation compared to midazolam, but not before ICU discharge.
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PMID:Sedation in PACU: the role of propofol. 1630 51

Patients with heart failure have a diminished cardiac reserve capacity that may be further compromised by anesthesia. In addition to depression of sympathetic activity, most anaesthetics interfere with cardiovascular performance, either by a direct myocardial depression or by modifying cardiovascular control mechanisms. Etomidate causes the least cardiovascular depression. It is popular for induction of anesthesia in cardiac-compromised patients; however, it is not suitable for maintenance of anesthesia because it depresses adrenocortical function. Ketamine has a favorable cardiovascular profile related to central sympathetic stimulation and inhibition of neuronal catecholamine uptake. These counteract its direct negative inotropic effect. In patients with a failing myocardium, however, the negative inotropic effects may be unmasked, resulting in deterioration in cardiac performance and cardiovascular instability. Propofol is the most popular intravenous anesthetic for maintenance of anesthesia. It does have a negative inotropic effect, but the net effect on myocardial contractility is insignificant at clinical concentrations, probably because of a simultaneous increase in the sensitivity of the myofilaments to Ca2+. Propofol protects the myocardium against ischemia-reperfusion injury, an action derived from its antioxidant and free-radical-scavenging properties as well as the related inhibition of the mitochondrial permeability transition pore. For intravenous anesthesia, propofol is always combined with an opioid. Opioids have relatively few cardiovascular side effects and, in particular, do not cause myocardial depression. Indeed, they are cardioprotective, with antiarrhythmic activity, and induce pharmacologic preconditioning of the myocardium by a mechanism similar to the inhalational anesthetics.
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PMID:Intravenous anesthesia for the patient with left ventricular dysfunction. 1670 33

Propofol has been an immensely successful anaesthetic induction agent but there is an increasing number of reports of serious complications when it has been used as an infusion to provide sedation for prolonged periods. The first reports involved children who died from intractable myocardial failure preceded by a metabolic acidosis, lipaemic plasma, fatty infiltration of the liver and evidence of muscle damage. As more cases have been reported the association between propofol and the syndrome has become more certain. Recently adult cases have appeared and a metabolic explanation has been suggested. The syndrome has a high mortality and the only effective treatment appears to be dialysis.
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PMID:The propofol infusion syndrome in infants and children: can we predict the risk? 1701 22

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.
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PMID:Propofol infusion syndrome: a case of increasing morbidity with traumatic brain injury. 1719 29

Propofol is increasingly used for the treatment of status epilepticus due to the ease of use and tolerability, even if safety data from randomized clinical trials are lacking. An association of high infusion rates of propofol (>5 mg/kg/h) for more than 48 h and constellation of acidosis, rhabdomyolysis, and cardiovascular collapse has been reported in children, but has only been described in a few adult cases. We report a case and autopsy findings of an adult who developed rhabdomyolysis and cardiac failure after receiving propofol for status epilepticus. The patient became symptomatic within 55 h after initiation of propofol infusion. The maximal infusion rate did not exceed 7.2 mg/kg/h, and propofol in excess of 5mg/kg/h was infused for less than 20 h. Preexisting antiepileptic medication may have exacerbated acidosis. Propofol infusion for the treatment of status epilepticus should be carefully weighted against its real risk to develop propofol infusion syndrome, and alternative agents such as benzodiazepines or barbiturates should be considered for first line therapy. If necessary, prolonged propofol infusion at high doses for the treatment of status epilepticus should be used with caution, and in all cases careful monitoring for rhabdomyolysis and acidosis must be performed.
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PMID:Propofol-associated fatal myocardial failure and rhabdomyolysis in an adult with status epilepticus. 1738 34

As oversedation is still common and significant variability between and within critically ill patients makes empiric dosing difficult, the population pharmacokinetics and pharmacodynamics of propofol upon long-term use are characterized, particularly focused on the varying disease state as determinant of the effect. Twenty-six critically ill patients were evaluated during 0.7-9.5 days (median 1.9 days) using the Ramsay scale and the bispectral index as pharmacodynamic end points. NONMEM V was applied for population pharmacokinetic and pharmacodynamic modeling. Propofol pharmacokinetics was described by a two-compartment model, in which cardiac patients had a 38% lower clearance. Severity of illness, expressed as a Sequential Organ Failure Assessment (SOFA) score, particularly influenced the pharmacodynamics and to a minor degree the pharmacokinetics. Deeper levels of sedation were found with an increasing SOFA score. With severe illness, critically ill patients will need downward titration of propofol. In patients with cardiac failure, the propofol dosages should be reduced by 38%.
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PMID:Disease severity is a major determinant for the pharmacodynamics of propofol in critically ill patients. 1865 Aug 1

Propofol infusion syndrome (PRIS) is a new clinical entity reported in critically ill patients. Lactic acidosis, cardiac failure and rhabdomyolysis are the features. Lactic acidosis related to short-term propofol administration has been described during general anaesthesia. Lactic acidosis could be an early marker of PRIS. We report here a case of very early lactic acidosis in a 66-year-old-man receiving propofol during a neurosurgery. The outcome was good after discontinuation of propofol.
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PMID:[Lactic acidosis associated with propofol during general anaesthesia for neurosurgery]. 1831 82


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