Propofol metabolic acidosis

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... 

Propofol is very lipid soluble, has a large volume of distribution, and has a rapid onset of action. It has comparable efficacy to midazolam for refractory GCSE. It has been associated with metabolic acidosis, hemodynamic instability, and bradyarrhythmias that are refractory to treatment. 

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. 

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. 

These cases are important because, unlike previous reports of metabolic acidosis after propofol infusion, the... 

Burow BK, Johnson ME, Packer DL. Metabolic acidosis associated with propofol in the absence of other causative factors. Anesthesiology 2004 101 239-41. 

Funston JS, Prough DS. Two reports of propofol anesthesia associated with metabolic acidosis in adults. Anesthesiology 2004 101 6-8. 

These cases are important because, unlike previous reports of metabolic acidosis after propofol infusion, the patients had no documented infections and, in at least one case, extensive investigation showed no other causes of the acidosis. The role of propofol in causing the metabolic problems appears to have been more likely in these than in previous reports. In the first three cases the doses of propofol used, both per hour and in all, were extremely high compared with normal therapeutic practice. The subject has also been reviewed, and it was pointed out that, although suggestive, the association of fatal metabolic acidosis with propofol infusion in sick patients is as yet unproven and to date hinges on 11 case reports of patients who had multiple problems (55). 

A 47-year-old woman had an infusion of propofol 200 micrograms/kg/minute for 4 days. On day 2 she developed hematuria, and laboratory investigations showed renal insufficiency with hyperkalemic metabolic acidosis. She died as a result of rhabdomyolysis with cardiac involvement. 

An 18-year-old man suffered multiple trauma (70). He was sedated for 98 hours with propofol 530-700 mg/ hour. On day 5 he developed a metabolic acidosis with hyperkalemia and his serum was Upemic. An... 

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. 

Cannon ML, Glazier SS, Bauman LA. Metabolic acidosis, rhabdomyolysis, and cardiovascular collapse after prolonged propofol infusion. J Neurosurg 2001 95(6) 1053-6. 

Propofol is extremely hpid soluble and has a large volume of distribution. It has a very rapid onset of action and an extremely short half-life (2 to 4 minutes), which promotes rapid awakening on drug discontinuation. Although extensive data are not available, it appears to be effective in GCSE. " Doses can be found in Table 55-4. It may cause respiratory and cerebral depression and bradycardia. Although metabolic acidosis has been reported, the occurrence of propofol-associated metabolic acidosis is controversial. Finally, a normal adult dose may provide over 1000 calories per day as lipid at a cost to the patient that may exceed 1000 per day. 

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... 

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... 

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. 

---