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PubMed2002

Antioxidant protection of propofol and its recycling in erythrocyte membranes.

alpha-Tocopherol is a potent antioxidant that effectively protects biological membranes against oxidative injury through coordination with ascorbic acid. Because propofol has a phenolic structure similar to that of alpha-tocopherol, this intravenous anesthetic may also have similar antioxidant activity. To test this hypothesis, the effect of propofol on oxidative injury of human erythrocytes was examined. Propofol inhibited oxidative hemolysis and cis-parinaric acid oxidation in erythrocyte membranes (ED(50) = 6 microM). Although ascorbic acid alone has no appreciable effect, the protective effect of propofol was enhanced by ascorbic acid. An electron spin resonance (ESR) study showed that propofol-derived radicals (g = 2.005) were continuously generated during the oxidation of erythrocyte membranes by an ascorbic acid-inhibitable mechanism. These and other results suggest that propofol interacts with ascorbic acid, thereby exhibiting potent antioxidant activity in and around membranes as does alpha-tocopherol. Kinetic analysis revealed that propofol increased the membrane fluidity of erythrocytes, thereby increasing their resistance to physical and hemodynamic stress. Further, a greater preservation of red blood cell counts was seen after surgery with propofol compared with conventional sevoflurane anesthesia. Thus, propofol may protect erythrocytes against both oxidative and physical stress, indicating its potential as an efficient and safe antioxidant.

Antioxidants↗
PubMed1999

Propofol-thiopentone admixture-hypnotic dose, pain on injection and effect on blood pressure.

This study examined some pharmacodynamic characteristics of two admixtures of propofol and thiopentone. Ninety unpremedicated ASA 1 or 2 patients were group-randomized to receive, in a double-blinded manner, one of the following mixtures for induction of anaesthesia: Group P50: propofol 1% 10 ml/thiopentone 2.5% 10 ml; Group P75: propofol 1% 15 ml/thiopentone 2.5% 5 ml; Group P100: propofol 1% 20 ml/lignocaine 1% 4 ml. An additional 30 randomized but unblinded patients from the same patient cohort received thiopentone 2.5% to provide predictive dose data for groups P50 and P75. Haemodynamic data were collected pre- and post-induction. The required induction dose of both mixtures of propofol and thiopentone found an additive rather than a synergistic interaction with no significant difference between predicted and observed dose. Thiopentone resulted in significantly more rapid induction of anaesthesia than propofol/lignocaine or propofol/thiopentone. The addition of thiopentone to propofol was found to be as efficacious as the mixing of lignocaine with propofol in reducing pain on injection. The fall in systolic blood pressure was significantly less in group P50 compared with groups P75 or P100. Admixture of thiopentone with propofol results in an additive hypnotic effect, a reduction in pain of injection (comparable with addition of lignocaine) and a reduced hypotensive response compared to propofol injection alone during induction.

Adolescent↗
PubMed2005

Propofol is cardioprotective in a clinically relevant model of normothermic blood cardioplegic arrest and cardiopulmonary bypass.

The general anesthetic propofol has been shown to be cardioprotective. However, its benefits when used in cardioplegia during cardiac surgery have not been demonstrated. In this study, we investigated the effects of propofol on metabolic stress, cardiac function, and injury in a clinically relevant model of normothermic cardioplegic arrest and cardiopulmonary bypass. Twenty anesthetized pigs, randomized to propofol treatment (n = 8) and control (n = 12) groups, were surgically prepared for cardiopulmonary bypass (CPB) and cardioplegic arrest. Doses of warm blood cardioplegia were delivered at 15-min intervals during a 60-min aortic cross-clamped period. Propofol was continuously infused for the duration of CPB and was therefore present in blood cardioplegia. Myocardial biopsies were collected before, at the end of cardioplegic arrest, and 20 mins after the release of the aortic cross-clamp. Hemodynamic parameters were monitored and blood samples collected for cardiac troponin I measurements. Propofol infusion during CPB and before ischemia did not alter cardiac function or myocardial metabolism. Propofol treatment attenuated the changes in myocardial tissue levels of adenine nucleotides, lactate, and amino acids during ischemia and reduced cardiac troponin I release on reperfusion. Propofol treatment reduced measurable hemodynamic dysfunction after cardioplegic arrest when compared to untreated controls. In conclusion, propofol protects the heart from ischemia-reperfusion injury in a clinically relevant experimental model. Propofol may therefore be a useful adjunct to cardioplegic solutions as well as being an appropriate anesthetic for cardiac surgery.

Anesthetics, Intravenous↗
PubMed2005

Propofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABA(A) receptor chloride channels.

Propofol is a widely used intravenous general anesthetic. Propofol-induced unconsciousness in humans is associated with inhibition of thalamic activity evoked by somatosensory stimuli. However, the cellular mechanisms underlying the effects of propofol in thalamic circuits are largely unknown. We investigated the influence of propofol on synaptic responsiveness of thalamocortical relay neurons in the ventrobasal complex (VB) to excitatory input in mouse brain slices, using both current- and voltage-clamp recording techniques. Excitatory responses including EPSP temporal summation and action potential firing were evoked in VB neurons by electrical stimulation of corticothalamic fibers or pharmacological activation of glutamate receptors. Propofol (0.6 - 3 microM) suppressed temporal summation and spike firing in a concentration-dependent manner. The thalamocortical suppression was accompanied by a marked decrease in both EPSP amplitude and input resistance, indicating that a shunting mechanism was involved. The propofol-mediated thalamocortical suppression could be blocked by a GABAA receptor antagonist or chloride channel blocker, suggesting that postsynaptic GABAA receptors in VB neurons were involved in the shunting inhibition. GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked in VB neurons by electrical stimulation of the reticular thalamic nucleus. Propofol markedly increased amplitude, decay time, and charge transfer of GABAA IPSCs. The results demonstrated that shunting inhibition of thalamic somatosensory relay neurons by propofol at clinically relevant concentrations is primarily mediated through the potentiation of the GABAA receptor chloride channel-mediated conductance, and such inhibition may contribute to the impaired thalamic responses to sensory stimuli seen during propofol-induced anesthesia.

Anesthetics, Intravenous↗
PubMed1993

Sedative doses of propofol increase beta activity of the processed electroencephalogram.

The effects of sedative infusions of propofol on the processed electroencephalograms (EEG) of eight healthy male volunteers were studied. EEG data for aperiodic analysis were collected during three 5-min periods: before propofol, during propofol infusion, and 30 min after termination of the infusion. After an initial dose of 1 mg/kg, subjects received a propofol infusion titrated to produce a standard level of conscious sedation. The infusion rate was 84 +/- 27 micrograms.kg-1 x min-1 (mean +/- SE) and plasma propofol levels were 2180 +/- 43 ng/mL. Total EEG power, defined as the sum of the squares of peak-to-peak amplitudes during each 5-s epoch, increased from 1350 +/- 295 microV2 x epoch-1 to 9675 +/- 2390 microV2 x epoch-1 during the propofol infusion (P < 0.05); it returned to 1445 +/- 145 microV2 x epoch-1 30 min after the infusion was discontinued (P < 0.05 vs the result during propofol). The change in total power was accompanied by a change in the distribution of power within the EEG spectrum, as the fraction of activity in the beta-band (12-35 Hz) increased during the infusion from 23% +/- 3% to 44% +/- 5% (P < 0.05). Thirty minutes after the infusion was terminated, the distribution of activity within the EEG spectrum had reverted to pre-propofol patterns. The similarity of EEG effects seen with sedative doses of propofol and benzodiazepines suggests that these drugs may share some neurochemical effects.

Adult↗
PubMed1994

Comparison of eltanolone and propofol in anesthesia for termination of pregnancy.

A randomized study was designed to compare eltanolone (pregnanolone) and propofol anesthesia in 60 unpremedicated women undergoing outpatient termination of pregnancy. The initial doses for induction of anesthesia were 0.8 mg/kg for eltanolone and 2 mg/kg for propofol followed by an additional 25% increment if necessary. The doses required for successful induction were 0.82 +/- 0.06 and 2.1 +/- 0.3 (mean +/- SD) mg/kg for eltanolone and propofol, respectively. Discomfort or pain on injection occurred in none of the patients given eltanolone and in 20% of those receiving propofol (P < 0.05). To maintain satisfactory anesthesia, 29% of the patients given eltanolone and 70% of the patients given propofol needed extra bolus doses of the study drug (P < 0.01). Excitation (twitching of extremities or slight hypertonus) occurred in 29% of the patients in the eltanolone group compared to none in the propofol group (P < 0.05). Both clinical (opening eyes, orientation, walking, tolerating oral fluids, voiding) and psychomotor recovery (Maddox Wing test and Digit Symbol Substitution test) returned to baseline more slowly after eltanolone than after propofol. Overall home readiness was achieved later in the eltanolone group [median 57 min (range 41-190 min)] compared to the propofol [37 (32-100 min)] group. We conclude that recovery from anesthesia is more rapid from propofol as compared to eltanolone anesthesia.

Abortion, Induced↗
PubMed2003

The contribution of the coronary concentrations of propofol to its cardiovascular effects in anesthetized sheep.

UNLABELLED: Linking physiological pharmacokinetic models to models of the cardiovascular system requires knowledge of the sites in the body that mediate a drug's cardiovascular effects. We examined the role of the coronary concentrations of propofol. Nine sheep anesthetized with isoflurane (2%) were instrumented acutely for cardiovascular measurements. In a random crossover design, they were administered ramped coronary artery (CA) infusions of propofol to selectively enrich the myocardium (as indicated by the coronary sinus blood concentration) or IV infusions to achieve the same concentration range in all sites of the body. Reductions in left ventricular myocardial contractility (LV dP/dt(max)) and mean arterial blood pressure were linearly related to the propofol concentration. For the CA route, LV dP/dt(max) was reduced by 52 mm Hg/s for each milligram per liter increase in coronary sinus propofol concentration. For the IV route, the reduction in LV dP/dt(max) was equivalent to that with the CA route, showing that the coronary propofol concentration was the major contribution to this effect. For the CA route, mean arterial blood pressure was reduced by 0.6 mm Hg for each milligram per liter. There was a larger reduction (2.5 mm Hg x mg(-1) x L(-1)) for the IV route. Therefore, this effect was predominantly mediated by propofol concentrations elsewhere in the body. IMPLICATIONS: With use of selective coronary artery infusions in sheep, the coronary concentrations of propofol were shown to be the major contributor to the cardiac depression caused by propofol but were a less significant contributor to the hypotension caused by this drug. Models of the cardiovascular effects of propofol should account for these relationships.

Anesthesia↗
PubMed2004

Pretreatment with thiopental for prevention of pain associated with propofol injection.

UNLABELLED: Propofol causes pain on IV injection in 28%-90% of patients. A number of techniques have been tried to minimize propofol-induced pain, with variable results. We compared the efficacy of pretreatment with thiopental 0.25 mg/kg and 0.5 mg/kg and lidocaine 40 mg after venous occlusion for prevention of propofol-induced pain. One-hundred-twenty-four adult patients, ASA physical status I-II, undergoing elective surgery were randomly assigned into 4 groups of 31 each. Group I received normal saline, group II received lidocaine 2% (40 mg), and groups III and IV received thiopental 0.25 mg/kg and 0.5 mg/kg, respectively. All pretreatment drugs were made in 2 mL and were accompanied by manual venous occlusion for 1 min. Propofol was administered after release of venous occlusion. Pain was assessed with a four-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe pain at the time of propofol injection. Twenty-four patients (77%) complained of pain in the group pretreated with normal saline as compared with 12 (39%), 10 (32%), and 1 (3%) in the groups pretreated with lidocaine 40 mg, thiopental 0.25 mg/kg, and thiopental 0.5 mg/kg, respectively (P < 0.05). Thiopental 0.5 mg/kg was the most effective treatment. We therefore suggest routine pretreatment with thiopental 0.5 mg/kg along with venous occlusion for 1 min for prevention of pain associated with propofol injection. IMPLICATIONS: Pain associated with IV injection of propofol is seen in 28%-90% patients. Pretreatment with thiopental 0.25 mg/kg and 0.5 mg/kg after manual venous occlusion for 1 min effectively attenuated pain associated with propofol injection. Thiopental 0.5 mg/kg was the most effective in prevention of propofol pain and can be used routinely.

Adult↗
PubMed2004

The effects of propofol on hypothalamic paraventricular nucleus neurons in the rat.

UNLABELLED: The mechanism of hypotension induced by anesthetics is not completely understood. Because no electrophysiologic examination of the effects of propofol on the central nervous system has shown its involvement in the control of sympathetic and cardiovascular functions, we investigated the actions of propofol on rat hypothalamic paraventricular nucleus (PVN) neurons using the whole-cell mode of the patch-clamp technique in rat hypothalamic PVN slice preparations. Propofol induced Cl(-) currents at concentrations of 10(-5) and 10(-4) M, which were sensitive to picrotoxin and, to a lesser extent, to strychnine. Propofol (10(-6) M) enhanced gamma-aminobutyric acid(A) (GABA(A); 10(-6) M)-induced current synergistically. Moreover, propofol (10(-5) and 10(-4) M) significantly increased the decay time of evoked-inhibitory postsynaptic currents, which suggests a postsynaptic modulation of GABA(A) receptors. In addition, propofol (10(-5), 10(-4), and 2 x 10(-4) M) reversibly inhibited voltage-gated Ca(2+) currents. Taken together, these results suggest that propofol enhancement of GABA(A)-receptor mediated currents and inhibition of voltage-gated Ca(2+) currents at the central level, which is involved in the control of cardiovascular and sympathetic functions may be, at least in part, involved in general anesthetic-induced cardiovascular and sympathetic depression. IMPLICATIONS: We investigated the actions of propofol on the rat hypothalamic paraventricular nucleus neurons, which are involved in the control of cardiovascular and sympathetic functions. The results suggest that propofol enhancement of gamma-aminobutyric acid(A)-receptor mediated currents and inhibition of voltage-gated Ca(2+) currents at the central level may be, at least in part, involved in general anesthetic-induced cardiovascular and sympathetic depression.

Anesthetics, Intravenous↗
PubMed2004

The recovery profile of reduced diaphragmatic contractility induced by propofol in dogs.

Propofol decreases contractility of the diaphragm, but no data are available for its effects on recovery. We studied the recovery profile of reduced diaphragmatic contractility induced by propofol in dogs. Animals were divided into 4 groups of 7 each. Group I, without fatigue, received only maintenance fluid; Group II, without fatigue, was infused with propofol; Group III, with fatigue, received no study drug; Group IV, with fatigue, was infused propofol. Propofol at an anesthetic dose (0.1 mg/kg initial dose plus 6.0 mg x kg(-1) x h(-1)) was administered for 60 min. In Groups III and IV, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at 20-Hz for 30 min. We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). In group II, Pdi at low-frequency (20-Hz) stimulation decreased to less than baseline (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. At 10 min after the end of propofol administration, Pdi at 20-Hz stimulation returned to baseline. When fatigue was established, in Groups III and IV, Pdi at 20-Hz stimulation decreased to less than baseline (P < 0.05), whereas Pdi at 100-Hz stimulation did not change. After administering propofol in Group IV, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05). At 20 min after the end of propofol administration, Pdi at 20-Hz stimulation returned to fatigued values. We conclude that reduced contractility in nonfatigued and fatigued canine diaphragm induced by propofol recovers within 20 min after the cessation of administration.

Anesthetics, Intravenous↗
PubMed2004

Propofol inhibits human platelet aggregation induced by proinflammatory lipid mediators.

Lysophosphatidic acid (LPA), platelet-activating factor (PAF), and thromboxane A(2) are proinflammatory lipid mediators that activate surface receptors on platelets, producing increased intracellular calcium, which is necessary for aggregation. We investigated propofol's effect on platelet aggregation and intracellular calcium mobilization caused by these three agonists. Platelets from human volunteers were incubated in buffers containing LPA (1 microM), U46619 (thromboxane A(2) analog; 1 microM), or PAF (10 nM). Propofol emulsion or 2,6-diisopropylphenol (propofol without fat emulsion) dissolved in ethanol was added to achieve concentrations of propofol used clinically: 5 or 10 microg/mL. After 2 min, aggregation or intracellular calcium concentrations were measured with optical techniques. Propofol emulsion and propofol in ethanol produced similar inhibition of platelet aggregation induced by LPA, PAF, and U46619 in a dose-dependent fashion. LPA, PAF, and U46619 each caused significant increases in intracellular calcium that were not modified by propofol. Because propofol does not significantly alter intracellular calcium increases caused by receptor activation, inhibition appears to act distal to platelet receptors, inositol phosphate 3, and phospholipase C. Because the three lipid mediators play a key role in inflammation, their inhibition by propofol might be clinically important.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2004

Thiopental and propofol affect different regions of the brain at similar pharmacologic effects.

Propofol has a greater amnesic effect than thiopental. In this study we tested whether different brain regions were affected by propofol and thiopental at similar drug effects. Changes in regional cerebral blood flow (rCBF) were identified by using SPM99 analysis of images obtained with positron emission tomography with (15)O water. Ten right-handed male volunteers (age, 35 +/- 10 yr; weight, 74.1 +/- 7.5 kg; mean +/- sd) were randomized to receive thiopental (n = 4) or propofol (n = 6) to target sedative and hypnotic concentrations with bispectral index (BIS) monitoring. Four positron emission tomography images were obtained during various tasks at baseline and with sedative and hypnotic effects. Two participants receiving propofol were unresponsive at sedative concentrations and were not included in the final analyses. Median serum concentrations were 1.2 and 2.7 microg/mL for sedative and hypnotic propofol effects, respectively. Similarly, thiopental concentrations were 4.8 and 10.6 microg/mL. BIS decreased similarly in both groups. The pattern of rCBF change was markedly different for propofol and thiopental. Propofol decreased rCBF in the anterior (right-sided during sedation) brain regions, whereas thiopental decreased rCBF primarily in the cerebellar and posterior brain regions. At similar levels of drug effect, propofol and thiopental affect different regions of the brain. These differences may help to identify the loci of action for the nonsedative effects of propofol, such as amnesia.

Adult↗
PubMed2006

Tolerance to propofol's sedative effect in mechanically ventilated Rabbits.

Propofol is commonly used for the sedation of critically ill patients undergoing mechanical ventilation. These patients may develop tolerance during long-term administration. Here, we describe the development of tolerance to propofol's sedative effect in rabbits during prolonged mechanical ventilation. Six healthy male New Zealand White rabbits were endotracheally intubated and received propofol by continuous IV infusion to maintain sedation for 48 h. The propofol infusion rate (IR) was adjusted to maintain the desired level of sedation. Assessments of the sedation level were made every 30 min or earlier if there were signs of awakening. Propofol concentrations were measured in arterial plasma after every other IR adjustment, provided there was an adequate level of sedation, using high performance liquid chromatography, and calculations of systemic clearance rates were made. The mortality rate was 100% with a survival period of 30.8 +/- 6.0 h (mean +/- sd). The course of IR adjustments followed a 5-phase pattern: 1) steady IR (mean +/- sd duration; 1.2 +/- 0.6 h), 2) increasing IR (9.4 +/- 5.5 h), 3) steady high-IR (2.3 +/- 1.2 h), 4) decreasing IR (13.7 +/- 1.9 h), and 5) steady low-IR (5.0 +/- 2.7 h). The course of propofol concentrations during the experiment in relation to propofol IR followed a 3-phase pattern: 1) steady concentration with increasing IRs (6.0 +/- 2.7 h), 2) increasing concentrations with increasing IR (5.8 +/- 2.5 h), and 3) increasing concentrations with decreasing IR (18.8 +/- 3.3 h). Propofol systemic clearance rates were progressively increased for 6.0 +/- 2.7 h and then gradually decreased for 24.6 +/- 4.7 h. In conclusion, all rabbits developed tolerance to propofol's sedative effect within the first hours of administration related to changes to the drug's metabolic clearance.

Animals↗
PubMed2002

Propofol infusion syndrome in critically ill patients.

OBJECTIVE: To describe the clinical presentation of propofol infusion syndrome in critically ill adults. DATA SOURCES: Clinical literature was accessed through MEDLINE (1966 - March 2001). Key search terms included Diprivan, propofol, and propofol infusion syndrome. Case reports and small case series evaluating the use and toxicity of propofol in sedating critically ill adults were reviewed. DATA SYNTHESIS: The association between propofol infusion syndrome and death in children secondary to myocardial failure is well documented. However, few data are available regarding the syndrome in critically ill adults. Based on a review of those data, it appears that propofol infusion syndrome can occur in both children and adults. Common clinical features of propofol infusion syndrome may include hyperkalemia, hepatomegaly, lipemia, metabolic acidosis, myocardial failure, and rhabdomyolysis. Although the premise has not been proven, recent published cases appear to demonstrate an association between propofol infusion and death secondary to myocardial failure. CONCLUSIONS: Until further safety data become available, caution should be exercised when using high-dose (>5 mg/kg/h) and long-term (>48 h) propofol infusion in sedating critically ill adults.

Adult↗
PubMed2002

Effects of propofol and taurine on intracellular free amino acid profiles and immune function markers in neutrophils in vitro.

We have examined the effects of propofol, taurine, and the combination of propofol and taurine on amino acid profiles and the immune function markers superoxide anion (O2-), hydrogen peroxide (H2O2), and released myeloperoxidase (MPO) activity in neutrophils (PMN). Propofol led to significant changes in the dynamic PMN-free amino acid pool. Exogenous taurine significantly reduced PMN neutral amino acid and alpha-aminobutyrate (alpha-aba) as intracellular taurine increased. Incubation with propofol plus taurine resulted in lower intracellular taurine levels and elevated alpha-aba and neutral amino acid concentrations compared to propofol alone. Concerning PMN immune function markers, propofol significantly decreased O2- and H2O2 formation and released MPO. Taurine led to an increased release of MPO and concomitant significantly reduced O2- and H2O2 levels. When propofol and taurine were applied together they appeared to act additively with regard to superoxide and hydrogen peroxide formation. In the case of MPO, taurine neutralized propofol's effects, supporting the idea that MPO activity may be regulated by taurine. We believe therefore that taurine is important for strengthening PMN host defense capability, although the mechanisms are not yet clear. Moreover, taurine appears to act primarily by altering the PMN osmotic balance, while propofol seems to affect PMN amino acid metabolism and/or uptake and release.

Adult↗
PubMed2002

Continuous propofol infusion in 142 critically ill children.

OBJECTIVE: In recent years, continuous intravenous propofol infusion has been widely used in pediatric intensive care units. Several case reports have raised concerns about its safety. The objective of this study was to report our experience with continuous intravenous propofol in consecutive patients during an 18-month period. METHODS: The study design was a retrospective review of a case series. Case was defined as a critically ill child who was treated with continuous intravenous propofol. The attending physician staff agreed to prescribe propofol via continuous intravenous infusion at a dose not to exceed 50 microg/kg/min. The protocol allowed for each patient to receive an additional intravenous bolus of propofol at a dose of 1 mg/kg no more than once per hour. The study entailed data collection from consecutive patients who were prescribed a continuous infusion of propofol in either the pediatric intensive care unit or bone marrow transplant unit. RESULTS: Data from 142 patients were analyzed. Each patient enrolled was adequately sedated. Administration of propofol via continuous intravenous infusion was not associated with metabolic acidosis or hemodynamic compromise. No patient in the study group was inadvertently extubated or had a central venous catheter accidentally discontinued. CONCLUSIONS: Propofol can be safely and effectively used to provide sedation to critically ill infants and children. We speculate that continuous infusion of propofol for extended periods of time should not exceed 67 microg/kg/min.

Acidosis↗
PubMed2005

Sedation in PACU: the role of propofol.

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.

Procedural Sedation↗
PubMed1999

The general anesthetic propofol slows deactivation and desensitization of GABA(A) receptors.

Propofol (2,6-di-isopropylphenol) has multiple actions on GABA(A) receptor function that act in concert to potentiate GABA-evoked currents. To understand how propofol influences inhibitory IPSCs, we examined the effects of propofol on responses to brief applications of saturating concentrations of GABA (1-30 mM). GABA was applied using a fast perfusion system to nucleated patches excised from hippocampal neurons. In this preparation, propofol (10 microM) had no detectable agonist effect but slowed the decay, increased the charge transfer (62%), and enhanced the peak amplitude (8%) of currents induced by brief pulses (3 msec) of GABA. Longer pulses (500 msec) of GABA induced responses that desensitized with fast (tau(f) = 1.5-4.5 msec) and slow (tau(s) = 1-3 sec) components and, after the removal of GABA, deactivated exponentially (tau(d) = 151 msec). Propofol prolonged this deactivation (tau(d) = 255 msec) and reduced the development of both fast and slow desensitization. Recovery from fast desensitization, assessed using pairs of brief pulses of GABA, paralleled the time course of deactivation, indicating that fast desensitization traps GABA on the receptor. With repetitive applications of pulses of GABA (0.33 Hz), the charge transfer per pulse declined exponentially (tau approximately 15 sec) to a steady-state value equal to approximately 40% of the initial response. Despite the increased charge transfer per pulse with propofol, the time course of the decline was unchanged. These experimental data were interpreted using computer simulations and a kinetic model that assumed fast and slow desensitization, as well as channel opening developed in parallel from a pre-open state. Our results suggest that propofol stabilizes the doubly liganded pre-open state without affecting the isomerization rate constants to and from the open state. Also, the rate constants for agonist dissociation and entry into the fast and slow desensitization states were reduced by propofol. The recovery rate constant from fast desensitization was slowed, whereas that from slow desensitization appeared to be unchanged. Taken together, the effects of propofol on GABA(A) receptors enhance channel opening, particularly under conditions that promote desensitization.

Anesthetics, General↗