Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent that is widely used in adults and children for sedation and the induction and maintenance of anaesthesia. Propofol has gained popularity for its rapid onset and rapid recovery even after prolonged use, and for the neuroprotection conferred. However, a review of the literature reveals multiple instances in which prolonged propofol administration (>48 hours) at high doses (>4 mg/kg/h) may cause a rare, but frequently fatal complication known as propofol infusion syndrome (PRIS). PRIS is characterized by metabolic acidosis, rhabdomyolysis of both skeletal and cardiac muscle, arrhythmias (bradycardia, atrial fibrillation, ventricular and supraventricular tachycardia, bundle branch block and asystole), myocardial failure, renal failure, hepatomegaly and death. PRIS has been described as an 'all or none' syndrome with sudden onset and probable death. The literature does not provide evidence of degrees of symptoms, nor of mildness or severity of signs in the clinical course of the syndrome. Recently, a fatal case of PRIS at a low infusion rate (1.9-2.6 mg/kg/h) has been reported. Common laboratory and instrumental findings in PRIS are myoglobinuria, downsloping ST-segment elevation, an increase in plasma creatine kinase, troponin I, potassium, creatinine, azotaemia, malonylcarnitine and C5-acylcarnitine, whereas in the mitochondrial respiratory electron transport chain, the activity of complex IV and cytochrome oxidase ratio is reduced. Propofol should be used with caution for sedation in critically ill children and adults, as well as for long-term anesthesia in otherwise healthy patients, and doses exceeding 4-5 mg/kg/h for long periods (>48 h) should be avoided. If PRIS is suspected, propofol must be stopped immediately and cardiocirculatory stabilization and correction of metabolic acidosis initiated. So, PRIS must be kept in mind as a rare, but highly lethal, complication of propofol use, not necessarily confined to its prolonged use. Furthermore, the safe dosage of propofol may need re-evaluation, and new studies are needed.
 ...
PMID:Propofol infusion syndrome: an overview of a perplexing disease. 2002 84

Propofol is a short-acting intravenous anesthetic agent widely used for sedation in anesthesia and intensive care. However, during the last 15 years there have been quite a lot of publications reporting unexplained deaths among pediatric and adult critically ill patients. These cases shared common symptoms and signs unrelated with initial admission diagnosis and were under long-term propofol infusion at high doses. A new syndrome called 'propofol infusion syndrome' was defined, including cardiovascular instability, metabolic acidosis, hyperkalaemia and rhabdomyolysis, with no evidence for other known causes of myocardial failure. One common denominator in these patients was the presence of hypoxia and tissue hypoperfusion. It seems that during states of increased metabolic demand, the reduced energy production related to an inhibitory propofol action at the level of mitochondrial oxidative phosphorylation and lipid metabolism may lead to the manifestation of the syndrome. Furthermore, cases of early toxicity due to failure in cellular energy production with development of lactic acidosis have been also described during anesthesia. For the above reasons, recommendations for the limitation of propofol use have been devised by various institutions, whereas physicians need to be cautious when using prolonged propofol sedation and alert for early signs of toxicity.
 ...
PMID:The propofol infusion 'syndrome' in intensive care unit: from pathophysiology to prophylaxis and treatment. 1865 4

Rapid sequence intubation is an essential bullet in the maintenance of patency of the airway during intubation in emergency. It is a valid method in all those situations where you can not determine whether the patient is fasting or not. But RSI is not applicable in all critically ill patients. The presence of severe acidosis, depletion of intravascular volume, heart failure and severe pulmonary disease may complicate the pre-induction period as the induction, leading to the onset of vasodilatation and hypotension. Another complication is represented by Hypoxemia during the manoeuvre. The algorithm of RSI consists in six steps: pre-oxygenation, premedication, myo-relaxation and induction, intubation, primary and secondary confirmation, post-intubation patient management. Propofol has replaced Thiopental as the most common intravenous ipnotic. In hypotensive patients Ketamine represents a viable alternative. Succinylcholine is the most common neuromuscular relaxant used in the RSI. The not depolarizing NMBAs are an alternative to Succinylcholine. Among these, the most important is the Rocuronium. This drug is characterized by a fairly rapid onset (1-2 min) and an intermediate half-life (45-70 min). The onset depends on the dosage used. The problem that limits the use of Rocuronium is the fact that its duration of action is much longer than that of Succinylcholine, especially when used at higher doses. This problem can be solved through the use of Sugammadex. As a muscle relaxant chelating Sugammadex antagonizes the effects induced by Rocuronium on muscle tissue and quickly resolve the blockade.
 ...
PMID:Rapid sequence intubation: a review of recent evidences. 2002 29

Propofol (2,6-diisopropylphenol) is administered intravenously for induction and maintenance of anesthesia; however, cases of progressive myocardial failure (propofol syndrome) related to the use of propofol have been reported. In the present study, the individual differences in pharmacokinetics and/or pharmacodynamics of propofol were investigated in patients who were genotyped for CYP2B6 and UGT1A9. Fifty-one patients treated with propofol in St. Marianna University Hospital were recruited for this study and provided written informed consent. The following parameters were analyzed: awakening time as a pharmacodynamic parameter, duration of propofol infusion, drug concentration in plasma after treatment, genotypes of CYP2B6 and UGT1A9, and age (42-84 years, mean of 65 years). Propofol was rapidly cleared from the blood of the subjects as a result of distribution and elimination. The awakening time after stopping propofol infusion was significantly correlated with the duration of infusion and the maximum concentration of propofol in these subjects. The maximum plasma concentration of propofol after normalizing with the duration of infusion was affected by the CYP2B6 G516T variant (related to impaired function) and was significantly affected by a propofol risk index score that incorporated CYP2B6 G516T and UGT1A9 I399C>T (high expression) genotypes and advanced age. These results provide important information indicating that the genotypes of the two enzymes studied and advanced age are combinative determinant factors of the pharmacokinetics and/or pharmacodynamics of propofol.
 ...
PMID:Individual differences in pharmacokinetics and pharmacodynamics of anesthetic agent propofol with regard to CYP2B6 and UGT1A9 genotype and patient age. 2186 35

Propofol infusion syndrome (PRIS) is a rare but often fatal complication as a result of large doses of propofol infusion (4-5 mg/kg/hr) for a prolonged period (>48 h). It has been reported in both children and adults. Besides large doses of propofol infusion, the risk factors include young age, acute neurological injury, low carbohydrate and high fat intake, exogenous administration of corticosteroid and catecholamine, critical illness, and inborn errors of mitochondrial fatty acid oxidation. PRIS manifestation include presence of metabolic acidosis with a base deficit of more than 10 mmol/l at least on one occasion, rhabdomyolysis or myoglobinuria, acute renal failure, sudden onset of bradycardia resistant to treatment, myocardial failure, and lipemic plasma. The pathophysiology of PRIS may be either direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. We report a case of supermorbidly obese patient who received propofol infusion by total body weight instead of actual body weight and developed PRIS.
 ...
PMID:Propofol infusion syndrome in a super morbidly obese patient (BMI = 75). 2209 79

Propofol is widely used for sedating critically ill adult patients because of its rapid onset and short recovery times, even after prolonged use. Propofol may be associated with a life-threatening syndrome, propofol-related infusion syndrome (PRIS), which includes cardiac failure, severe metabolic acidosis, renal failure, and rhabodomyolysis. The pathophysiology is incompletely understood. Propofol-related infusion syndrome seems to be dose-related, and it occurs generally in patients undergoing long-term (> 48 hrs) sedation at higher doses (> 4 mg/kg/hr). A case of PRIS in a patient after severe head injury is presented.
 ...
PMID:Propofol-related infusion syndrome induced by "moderate dosage" in a patient with severe head trauma. 2228 19

Myorelaxants use decrease trend appeared since the end of 80 years of the 20th century. The trend is connected with use of the new narcotic analgesics (Remifentanil), intravenous (Propofol) and inhalation (Sevoflurane) anaesthetics. These drugs are manageable and predictable, they have not many side effects and can suppress laryngeal-pharyngeal reflex during the tracheal intubation. Furthermore there are other factors such as succinylcholines use when fast intubation is needed, the wrong myorelaxant and dosage choice. Residual curarization and side effects risk increases due to these factors. As a result the patient's activation is delayed. Nevertheless myorelaxants use refusal impairs the tracheal intubation conditions, increases the arterial hypotension and heart failure risk especially in newborns and children with severe pathology. If myorelaxants is not used, comfortable conditions of surgical manipulations impossible without big analgesics and anaesthetics doses use.
 ...
PMID:[Modern approach to the neuromuscular blocking agents use in pediatric patients]. 2380 46

In this article, we present the case of a previously well 31-year-old man who sustained a mild closed-head injury following a motor vehicle incident and was admitted to the intensive care unit of a major teaching hospital. The man was sedated using propofol combined with midazolam and morphine as the main sedating agent. The propofol was started and continued at high dose for 8 days, over which time the patient deteriorated with metabolic acidosis, rhabdomyolysis, renal impairment, and cardiovascular collapse and then died. A forensic autopsy was performed. The only positive autopsy finding was a cardiac perivascular and interstitial infiltrate of mononuclear cells. The clinical and pathological features in the case presented were consistent with propofol infusion syndrome. No other cause for the above features was found and the cause of death was given as death related to propofol infusion syndrome.Propofol infusion syndrome is characterized by metabolic acidosis, rhadbomyolysis, and myocardial failure, sometimes with renal failure and hyperkalemia occurring in the setting of high-dose propofol treatment. The syndrome has become increasingly recognized in recent years. The syndrome is of importance to forensic pathologists who may see cases referred to their practice because of the unexplained deterioration of a patient in the intensive care unit and the association with head-injured patients and the pediatric population. Death associated with propofol infusion has not been described in the forensic literature.
...
PMID:Propofol infusion syndrome. 2586 75

Oxidative stress contributes to myocardial ischemia-reperfusion injury, which causes cardiomyocyte death and precipitate life-threatening heart failure. Propofol has been proposed to protect cells or tissues against oxidative stress. However, the mechanisms underlying its beneficial effects are not fully elucidated. In the present study, we employed an in vitro oxidative injury model, in which rat cardiac H9c2 cells were treated with H2O2, and investigated roles of propofol against oxidative stress. Propofol treatment reduced H2O2-induced apoptotic cell death. While H2O2 induced expression of the antioxidant enzyme HO-1, propofol further increased HO-1 mRNA and protein levels. Propofol also promoted nuclear localization of Nrf2 in the presence of H2O2. Knockdown of Nrf2 using siRNA suppressed propofol-inducible Nrf2 and expression of Nrf2-downstream antioxidant enzyme. Knockdown of Nrf2 suppressed the propofol-induced cytoprotection. In addition, Nrf2 overexpression induced nuclear localization of Nrf2 and HO-1 expression. These results suggest that propofol exerts antioxidative effects by inducing nuclear localization of Nrf2 and expression of its downstream enzyme in cardiac cells. Finally, we examined the effect of propofol on cardiomyocytes using myocardial ischemia-reperfusion injury models. The expression level of Nrf2 protein was increased at 15 min after reperfusion in the ischemia-reperfusion and propofol group compared with ischemia-reperfusion group in penumbra region. These results suggest that propofol protects cells or tissues from oxidative stress via Nrf2/HO-1 cascade.
 ...
PMID:Propofol induces nuclear localization of Nrf2 under conditions of oxidative stress in cardiac H9c2 cells. 2968 82

Propofol infusion syndrome (PRIS) is a rare syndrome originally described in critically ill children undergoing long-term (> 48 h) propofol infusion at high doses (> 4 mg/kg/h). Severe metabolic acidosis, rhabdomyolysis, renal failure and fatal cardiac failure are the features. Herein, we present a case of a newborn who developed PRIS after a single bolus dose of propofol at 3.2 mg/kg/do, developing rhabdomyolysis and severe metabolic acidosis, with a successful outcome after medical therapy.
 ...
PMID:Single dose of propofol causing propofol infusion syndrome in a newborn. 2994 32


<< Previous 1 2 3 Next >>