Propofol infusion syndrome

Propofol infusion syndrome has been described and may result in severe metabolic acidosis, cardiac dysrhythmias, cardiovascular collapse, rhabdomyolysis, and death. The risk may be increased with concomitant catecholamine infusions or when the dose exceeds... 

Diprivan) 40 mg every 1 0 seconds titrated to EEG) depression intubation high lipid load (increased calories) propofol infusion syndrome... 

Kang TM Propofol infusion syndrome in critically ill patients. Ann Pharmacother 2002 36 1453. [PMID 12196066]... 

Propofol infusion syndrome is a syndrome of cardiac failure (bradycardia, hypotension, low cardiac output), metabolic acidosis, and rhabdomyolysis, first described in children receiving high-dose propofol infusions for more than 48 hours. 

Although it was initially recognized in children, the propofol infusion syndrome is now known to occur in both children (950,951) and adults (952). 

Three fatal cases of propofol infusion syndrome in adults have been reported (953) a 27-year-old woman who developed a metabolic acidosis, hypotension, and bradycardia ... 

Propofol infusion syndrome can present with one component only, such as lactic acidosis (954) or rhabdomyolysis (955) (see below). It has been suggested that patients who are susceptible to metabolic acidosis or rhabdomyolysis after propofol administration may have subclinical forms of mitochondrial diseases that affect either the respiratory chain complex or fatty acid oxidation (956). In order to minimize the development of propofol infusion syndrome as a potentially lethal complication, a maximum dose of 3 mg/kg/hour has been recommended for sedation in intensive care patients. 

Propofol infusion syndrome might be precipitated by a combination of prolonged propofol infusion and carbohydrate intake insufficient to suppress fat metabolism. Support for this hypothesis has come from a case report of a child with catastrophic epilepsy who developed fatal propofol infusion syndrome after a ketogenic diet was introduced in an attempt to control severe intractable epilepsy (962). 

The use of extracorporeal cardiac support in the successful management of the cardiac failure associated with propofol infusion syndrome has been described (963). 

A 13-year-old boy underwent a 17-hour craniotomy in an attempt to resect an arteriovenous malformation with propofol-based anesthesia. He developed frank propofol infusion syndrome after 74 hours of postoperative propofol sedation in the neurosurgical ICU (used to manage intracranial hypertension). Echocardiography showed severe biventricular dysfunction despite extraordinary pharmacological support. Extracorporeal circulation with membrane oxygenation (ECMO) was instituted at the bedside via cannulation of the left femoral vessels. Hemofiltration... 

Hansen TG. [Propofol infusion syndrome in children.] Ugeskr Laeger 2005 167(39) 3672-5. 

Hantson P. Propofol infusion syndrome associated with short-term large-dose infusion during surgical anesthesia in an adult. Anesth Analg 2005 100 1804-6. 

Haase R, Sauer H, Eichler G. Lactic acidosis following short-term propofol infusion may be an early warning of propofol infusion syndrome. J Neurosurg Anesthesiol... 

Baumeister FAM, Oberhoffer R, Liebhaber GM, Kunkel J, Eberhardt J, Holthausen H, Peters J. Fatal propofol infusion syndrome in association with ketogenic diet. Neuropediatrics 2004 35 250-2. 

The propofol-infusion syndrome consists of a metabolic acidosis, rhabdomyolysis, and cardiovascular collapse. It occurs after prolonged infusion of propofol (over 48 hours) and has generally been reported in children, but also occasionally in adults. 

Propofol infusion syndrome mimics the mitochondrial myopathies, in which there are specific defects in the mitochondrial respiratory chain. The clinical features of mitochondrial myopathy result from a disturbance in lipid metabolism in cardiac and skeletal muscle. These patients generally remain well until stressed by infection or starvation, although subclinical biochemical abnormalities of mitochondrial transport can be demonstrated. It has been suggested that early management of critically iU children may not include adequate calorific intake to balance the increase in metabolic demands, and that in susceptible children the diversion of metabolism to fat substrates may cause the propofol infusion sjmdrome. It is unclear if the dose or duration of propofol infusion alters this effect. As adults have larger carbohydrate stores and require lower doses of propofol for sedation, this may account for the relative rarity of the sjmdrome in adults. The authors suggested that adequate early carbohydrate intake may prevent the propofol infusion syndrome (71). 

In a subsequent retrospective cohort analysis the odds ratio for the propofol infusion syndrome was 1.93 (95% Cl = 1.12, 3.32) for every 1 mg/kg/hour increase in mean propofol dose above 5 mg/kg/hour. The authors suggested that propofol infusion at rates over 5 mg/kg/hour should be discouraged for long-term sedation. 

A 13-year-old girl with a head injury, who received a high-dose infusion of propofol for 4 days, developed the propofol infusion syndrome (73). 

These findings are consistent with impaired fatty-acid oxidation reduced mitochondrial entry of long-chain acylcarnitine esters due to inhibition of the transport protein (carnitine palmityl transferase 1) and failure of the respiratory chain at complex II. Another previously reported abnormality of the respiratory chain in propofol-infusion syndrome is a reduction in cytochrome C oxidase activity, with reduced complex IV activity and a reduced cytochrome oxidase ratio of 0.004. Propofol can also impair the mitochondrial electron transport system in isolated heart preparations. 

Wolf A, Weir P, Segar P, Stone J, Shield J. Impaired fatty acid oxidation in propofol infusion syndrome. Lancet 2001 357(9256) 606-7. 

D. Propofol infusion syndrome, a condition of metabolic (lactic) acidosis, renal failure, rhabdomyolysis, and cardiovascular collapse, has been reported after prolonged hIgh-dose infusion in both pediatric and adult populations. 

Metabolism The propofol infusion syndrome has been predominantly reported anecdotally. Now the incidence has been assessed in a prospective, multicenter, observational study in 1017 patients who received propofol for at least 24 hours [41 ]. The syndrome was defined as a metabolic acidosis plus cardiac dysfunction plus one or more of rhabdomyolysis, hypertriglyceridemia, and renal failure. The criteria were satisfied in 11 patients (1.1%) 2 developed 3 criteria within 24 hours of propofol infusion and 10 developed three criteria within 3 days. Susceptibility factors were identified 10 of the 11 patients... 

The EIDOS and DoTS classifications of the propofol infusion syndrome are shown in Figure 1. 

Noradrenaline cardiac ischemia Propofol infusion syndrome Statins muscle damage... 

Propofol infusion syndrome Propofol infusion syndrome has been reported in children and adults after short-term high-dose propofol. It presents with variations of severe metabolic acidosis, rhabdomyolysis, myoglobinuria, cardiac failure, and death. The pathophysiology is unknown, but genetic predisposition, mitochondrial inhibition, and increases in serum free fatty acids are believed to play a role. Catecholamines and corticosteroids may act as triggering agents. 

In an analysis of 1139 patients with suspected propofol infusion syndrome in adults (mean age 52 years) and children (mean age 9 years), the presenting symptoms included cardiac (43%), hypotension (34%), rhabdomyolysis (27%), hepatic (24%), renal (24%), metabolic acidosis (20%), hypoxia (18%), and hyperthermia (12%) [74 ]. Propofol infusion ranges exceeded 5 mg/kg/hour in 129 cases in which the dose was reported. Regrettably, two important variables with respect to the propofol infusion syndrome, dosage and timing of propofol infusion, were not recorded in about 90% of papers. Multivariate logistic regression analysis identified... 

Two cases of propofol infusion syndrome in children undergoing cardiac surgery have been reported after short infusions of average doses of propofol. The diagnosis was based on the absence of other causes and abrupt resolution on drug withdrawal. A possible cause in this case was the combination of propofol with an inadequate carbohydrate intake to suppress fat metabolism [76" ]. 

Hyas MI, Balacumaraswami L, PaUn C, Ratnatunga C. Propofol infusion syndrome in adult cardiac surgery. Ann Thorac Surg 2009 87(1) el-3. 

Fong JJ, Sylvia L, Ruthazer R, Schumaker G, Kcomt M, Devlin JW. Predictors of mortality in patients with suspected propofol infusion syndrome. Crit Care Med 2008 36(8) 2281-7. 

Smith H, Sinson G, Varelas P. Vasopressors and propofol infusion syndrome in severe head trauma. Neurocrit Care 2009 10(2) 166-72. 

Laquay N, Pouard P, Silicani MA, Vaccaroni L, Orliaguet G. Early stages of propofol infusion syndrome in paediatric cardiac surgery two cases in adolescent girls. Br J Anaesth 2008 101(6) 880-1. 

Mijzen EJ, Jacobs B, Aslan A, Rodgers MG. Propofol infusion syndrome heralded by ECG changes. Neurocrit Care 2012 17 260-4. 

Vanlander AV, Jorens PG, Smet J, De Paepe B, Verbrugghe W, Van den Eynden GG, et al. Inborn oxidative phosphorylation defect as risk factor for propofol infusion syndrome. Acta Anaesthesiol Scand 2012 56 520-5. 

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