Propofol dosage

A. Additive effect with other CNS depressants that may result in lower propofol dosage requirements if given concomitantly. Through its inhibition of cytochrome P-450, propofol may increase levels of midazolam, diazepam, and other opiates such as sufentanyl and alfentanyl, causing respiratory depression, bradycardia, and hypotension. 

Refractory status epilepticus that has failed to respond to one of these treatments, and has continued for more than 20-30 min, requires urgent action. The accepted strategy is to paralyze and ventilate the patient and administer an antiepileptic drug in sufficient dosage to suppress EEG evidence of seizure activity. The barbiturate anaesthetic thiopental (thiopentone), the benzodiazepine midazolam, and the anaesthetic propofol have all been used. What little comparative evidence there is remains inconclusive. Such treatment can only be carried out with facilities for artificial ventilation and intensive care, and effects can only be monitored by EEG recording. 

Two LC methods have been reported for determining rocuronium bromide in pharmaceutical dosage forms [12,13]. The first method reported was used to examine the stability of a propofol-rocuronium mixture, a mixture employed for the rapid induction of anesthesia. In this method, a /iBondapak CN column (150 mm x 3.9 mm i.d.) was used as the stationary phase. A standard mixture of rocuronium bromide and propofol was prepared in acetonitrile, having 5 3 proportion of rocuronium bromide and propofol, respectively. The mobile phase consisted of 60 40 (v/v) acetonitrile/water, and the wavelength detection was set at 220 nm. It was found that in this mixture, rocuronium bromide was stable up to 48 h after mixing [13]. 

In 113 patients undergoing general anesthesia, intravenous midazolam 15 mg slowed recovery of the twitch height after vecuronium and atracurium compared with diazepam. The recovery index was not altered (162). However, in another study in 20 patients, midazolam 0.3 mg/kg did not affect the duration of blockade, recovery time, intensity of fasciculations, or adequacy of relaxation for tracheal intubation produced by suxamethonium 1 mg/kg, nor the duration of blockade and adequacy of relaxation for tracheal intubation produced by pancuronium 0.025 mg/kg in incremental doses until 99% depression of muscle-twitch tension was obtained (161). Furthermore, in 60 patients undergoing maintenance anesthesia randomly assigned to one of six regimens (etomidate, fentanyl, midazolam, propofol, thiopental plus nitrous oxide, or isoflurane plus nitrous oxide), midazolam did not alter rocuronium dosage requirements (165). 

The protease inhibitor saquinavir, propofol, and fluconazole (53,58,59) increased the systemic availability and peak plasma concentrations and prolonged the half-life of midazolam, thus increasing its sedative effects. The dosage of midazolam should be reduced in patients taking these drugs. 

Emulsions - liquid dispersions usually of an oil phase and an aqueous phase - are a traditional pharmaceutical dosage form. Oil-inwater systems have enjoyed a renaissance as vehicles for the delivery of lipid-soluble dmgs (e.g. propofol). Their use as a dosage form necessitates an understanding of the factors governing the formulation and stability of oil-in-water (o/w) and water-in-oil (w/o) emulsions, multiple emulsions (w/o/w or o/w/o) and microemulsions, which occupy a position between swollen micelles and emulsions with very small globule sizes. Photomicrographs of o/w, w/o systems and multiple emulsions are shown in Fig. 7.10. It is also possible to formulate nonaqueous or anhydrous emulsions, that is oil-in-oil systems and even multiple oil-in-oil-in-oil systems. 

Bailey, L.C. Tang, K.T. Rogozinski, B.A. The determination of 2,6-diisopropylphenol (propofol) in an oil in water emulsion dosage form by high-performance liquid chromatography and by second derivative UV spectroscopy. J.Pharm.Biomed.Anal., 1991, 9, 501-506 Chan, K. So, A.P. The measurement of propofol in human blood samples by liquid chromatography. 

VI. Dosage and method of administration. Propofol is currently administered as... 

The dosage of propofol may need to be reduced after the use of bupivacaine or lidocaine (e.g. during regional anaesthetic techniques). Similarly, epidural lidocaine reduces sevoflurane requirements, and is likely to have the same effect on other inhalational anaesthetics. 

Metoclopramide pre-treatment reduces the dosage requirements of propofol and thiopental. Droperidol, but not ondansetron, reduces the dose requirements of thiopentaL... 

Patients anaesthetised with inhalational anaesthetics (particularly cyclopropane and halothane, and to a lesser extent desflurane, enflurane, ether, isoflurane, methoxyflurane, and sevoflurane) can develop cardiac arrhythmias if they are given adrenaline (epinephrine) or noradrenaline (norepinephrine), unless the dosages are very low. Children appear to be less susceptible to this interaction. file addition of adrenaline to intrathecal tetracaine enhances the sedative effects of propofol. 

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... 

Barbiturates versus propofol The ECT data from two psychiatric units have been retrospectively compared [76 ]. In one unit propofol and succinylcholine is the anaesthetic regimen employed and the other unit uses thiopental and succinylcholine. The data, retrospectively collected over a 2 year period from 109 patients and 1538 ECT applications, reports a longer seizure duration with thiopental than propofol. However, more cardiovascular and respiratory complications were reported with thiopental than propofol. The study is limited by the retrospective collection of data, the variety of psychiatric conditions for which ECT was prescribed, and the lack of information about drug dosage schedules. 

Aimecke T, Conzen P, Ney L. Propofol-rdated infusion syndrome induced by "moderate dosage" in a patient with severe head trauma. J Chn Anesth2012 24 51. ... 

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