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PubMed2002

Non-steady state analysis of the pharmacokinetic interaction between propofol and remifentanil.

BACKGROUND: The pharmacokinetics of both propofol and remifentanil have been described extensively. Although they are commonly administered together for clinical anesthesia, their pharmacokinetic interaction has not been investigated so far. The purpose of the current investigation was to elucidate the nature and extent of pharmacokinetic interactions between propofol and remifentanil. METHODS: Twenty healthy volunteers aged 20-43 yr initially received either propofol or remifentanil alone in a stepwise incremental and decremental fashion a target controlled infusion. Thereafter, the respective second drug was infused to a fixed target concentration in the clinical range (0-4 microg/ml and 0-4 ng/ml for propofol and remifentanil, respectively) and the stepwise incremental pattern repeated. Frequent blood samples were drawn for up to 6 h for propofol and 40 min for remifentanil after the end of administration and assayed for the respective drug concentrations with gas chromatography-mass spectrometry. The time courses of the measured concentrations were fitted to standard compartmental models. Calculations were performed with NONMEM. After having established the individual population models for both drugs and an exploratory analysis for hypothesis generation, pharmacokinetic interaction was identified by including an interaction term into the population model and comparing the value of the objective function in the presence and absence of the respective term. RESULTS: The concentration-time courses of propofol and remifentanil were described best by a three- and two-compartment model, respectively. In the concentration range examined, remifentanil does not alter propofol pharmacokinetics. Coadministration of propofol decreases the central volume of distribution and distributional clearance of remifentanil by 41% and elimination clearance by 15%. This effect was not concentration-dependent in the examined concentration range of propofol. CONCLUSIONS: Coadministration of propofol decreases the bolus dose of remifentanil needed to achieve a certain plasma-effect compartment concentration but does not alter the respective maintenance infusion rates and recovery times to a clinically significant degree.

Adult↗

PubMed2002

Propofol: relation between brain concentrations, electroencephalogram, middle cerebral artery blood flow velocity, and cerebral oxygen extraction during induction of anesthesia.

BACKGROUND: The potential benefit of propofol dose regimens that use physiologic pharmacokinetic modeling to target the brain has been demonstrated in animals, but no data are available on the rate of propofol distribution to the brain in humans. This study measured the brain uptake of propofol in humans and the simultaneous effects on electroencephalography, cerebral blood flow velocity (V(mca)), and cerebral oxygen extraction. METHODS: Seven subjects had arterial and jugular bulb catheters placed before induction. Electroencephalography and V(mca) were recorded during induction with propofol while blood samples were taken from both catheters for later propofol analysis. Brain uptake of propofol was calculated using mass balance principles, with effect compartment modeling used to quantitate the rate of uptake. RESULTS: Bispectral index (electroencephalogram) values decreased to a minimum value of approximately 4 at around 7 min from the onset of propofol administration and then slowly recovered. This was accompanied by decreases in V(mca), reaching a minimum value of approximately 40% of baseline. Cerebral oxygen extraction did not change, suggesting parallel changes in cerebral metabolism. There was slow equilibrium of propofol between the blood and the brain (t(1/2keo) of 6.5 min), with a close relation between brain concentrations and bispectral index, although with considerable interpatient variability. The majority of the decreases in V(mca), and presumably cerebral metabolism, corresponded with bispectral index values reaching 40-50 and the onset of burst suppression. CONCLUSION: Description of brain distribution of propofol will allow development of physiologic pharmacokinetic models for propofol and evaluation of dose regimens that target the brain.

Adult↗

PubMed2004

Propofol modulates gamma-aminobutyric acid-mediated inhibitory neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

BACKGROUND: Although it is well recognized that anesthetics modulate the central control of cardiorespiratory homeostasis, the cellular mechanisms by which anesthetics alter cardiac parasympathetic activity are poorly understood. One common site of action of anesthetics is inhibitory neurotransmission. This study investigates the effect of propofol on gamma-aminobutyric acid-mediated (GABAergic) and glycinergic neurotransmission to cardiac parasympathetic neurons. METHODS: Cardiac parasympathetic neurons were identified in vitro by the presence of a retrograde fluorescent tracer, and spontaneous GABAergic and glycinergic synaptic currents were examined using whole cell patch clamp techniques. RESULTS: Propofol at concentrations of 1.0 microm and greater significantly (P < 0.05) increased the duration and decay time of spontaneous GABAergic inhibitory postsynaptic currents. To determine whether the action of propofol was at presynaptic or postsynaptic sites, tetrodotoxin was applied to isolate miniature inhibitory postsynaptic currents. Propofol at concentrations of 1.0 microm and greater significantly (P < 0.05) prolonged the decay time and duration of miniature inhibitory postsynaptic currents, indicating that propofol directly alters GABAergic neurotransmission at a postsynaptic site. Propofol at high concentrations (> or =50 microm) also inhibited the frequency of both GABAergic inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents. Propofol at concentrations up to 50 microm had no effect on glycinergic neurotransmission. CONCLUSIONS: Propofol may vary heart rate by modulating GABAergic neurotransmission to cardiac parasympathetic neurons. At clinically relevant concentrations (> or =1.0 microm), propofol facilitated GABAergic responses in cardiac vagal neurons by increasing decay time, which would increase inhibition of cardioinhibitory cardiac vagal neurons and evoke an increase in heart rate. At higher supraclinical concentrations (> or =50 microm), propofol inhibits GABAergic neurotransmission to cardiac vagal neurons, which would evoke a decrease in heart rate.

Animals↗

PubMed2004

A brief regional ischemic-reperfusion enhances propofol-induced depression in left ventricular function of in situ rat hearts.

BACKGROUND: Propofol is short-acting intravenous general anesthetics that reduces cardiovascular hemodynamics. The effects of propofol on intrinsic myocardial contractility, however, remain debatable. The aim of the current study was to test the hypothesis that inhibitory effects of propofol on left ventricular (LV) contractility and mechanical work capability of in situ ejecting rat hearts are attenuated after a brief regional ischemia and reperfusion. METHODS: The authors obtained steady-state LV pressure-volume loops and intermittently obtained LV end-systolic pressure-volume relation and evaluated effects of propofol on LV function by end-systolic pressure (ESPmLVV), systolic pressure-volume area (PVAmLVV) at midrange LV volume (mLVV). RESULTS: Propofol (5.2 +/- 0.3 approximately 11.1 +/- 3.7 microg.ml) significantly decreased ESP0.08 to 78 +/- 12% approximately 64 +/- 13% of prepropofol and PVA0.08 to 76 +/- 13%approximately 63 +/- 16% of prepropofol in normal hearts, whereas propofol at a lower concentration (4.1 +/- 1.0 microg/ml) did not. Although brief ischemic-reperfusion per se did not affect LV function, propofol after that, even at a lower concentration (4.1 +/- 1.0 microg/ml), significantly decreased ESP0.08 to 70 +/- 27% of prepropofol and PVA0.08 to 68 +/- 33% of prepropofol. Pretreatment with a protein kinase C (PKC) inhibitor, bisindolylmaleimide reduced the propofol (4.1 +/- 1.0 microg/ml)-induced greater decreases in ESP0.08 and PVA0.08 after brief ischemic-reperfusion to 94 +/- 33% and 92 +/- 39% of prepropofol. In the propofol-infused hearts after brief ischemic-reperfusion, protein kinase C-epsilon translocation to the nucleus-myofibril fraction was found. CONCLUSION: In contrast to the study hypothesis, brief ischemic-reperfusion enhanced the inhibitory effects of propofol on LV systolic function; this enhancement is attributable to activation of protein kinase C.

Anesthetics, Intravenous↗

PubMed2004

Propofol and sevoflurane depress spinal neurons in vitro via different molecular targets.

BACKGROUND: The capacity of general anesthetics to produce immobility is primarily spinally mediated. Recently, compelling evidence has been provided that the spinal actions of propofol involve gamma-aminobutyric acid type A (GABAA) receptors, whereas the contribution of glycine receptors remains uncertain. The relevant molecular targets of the commonly used volatile anesthetic sevoflurane in the spinal cord are largely unknown, but indirect evidence suggests a mechanism of action distinct from propofol. METHODS: The effects of sevoflurane and propofol on spontaneous action potential firing were investigated by extracellular voltage recordings from ventral horn interneurons in cultured spinal cord tissue slices obtained from embryonic rats (embryonic days 14-15). RESULTS: Propofol and sevoflurane reduced spontaneous action potential firing of neurons. Concentrations causing half-maximal effects (0.11 microm propofol, 0.11 mm sevoflurane) were lower than the median effective concentration immobility (1-1.5 microm propofol, 0.35 mm sevoflurane). At higher concentrations, complete inhibition of action potential activity was observed with sevoflurane but not with propofol. Effects of sevoflurane were mediated predominantly by glycine receptors (45%) and GABAA receptors (38%), whereas propofol acted almost exclusively via GABAA receptors (96%). CONCLUSIONS: The authors' results suggest that glycine and GABAA receptors are the most important molecular targets mediating depressant effects of sevoflurane in the spinal cord. They provide evidence that sevoflurane causes immobility by a mechanism distinct from the actions of the intravenous anesthetic propofol. The finding that propofol acts exclusively via GABAA receptors can explain its limited capacity to depress spinal neurons in the authors' study.

Action Potentials↗

PubMed2005

Human kidneys play an important role in the elimination of propofol.

BACKGROUND: Extrahepatic clearance of propofol has been suggested because its total body clearance exceeds hepatic blood flow. However, it remains uncertain which organs are involved in the extrahepatic clearance of propofol. In vitro studies suggest that the kidneys contribute to the clearance of this drug. The purpose of this study was to confirm whether human kidneys participate in propofol disposition in vivo. METHODS: Ten patients scheduled to undergo nephrectomy were enrolled in this study. Renal blood flow was measured using para-aminohippurate. Anesthesia was induced with vecuronium (0.1 mg/kg) and propofol (2 mg/kg) and then maintained with nitrous oxide (60%), sevoflurane (1 approximately 2%) in oxygen, and an infusion of propofol (2 mg . kg . h). Radial arterial blood for propofol and para-aminohippurate analysis was collected from a cannula inserted in the radial artery. The renal venous sample and the radial arterial sample were obtained at the same time after the steady state of propofol was established. RESULTS: The renal extraction ratio of propofol was 0.58 +/- 0.15 (mean +/- SD). The renal clearance of propofol was 0.41 +/- 0.15 l/min (mean +/- SD), or 27 +/- 9.9% (mean +/- SD) of total body clearance. CONCLUSION: Human kidneys play an important role in the elimination of propofol.

Aged↗

PubMed2005

Propofol inhibits long-term potentiation but not long-term depression in rat hippocampal slices.

BACKGROUND: Although propofol is known to produce amnesia when used for anesthesia, mechanisms underlying its effects on memory are poorly understood. The current study was designed to examine the effects of propofol on forms of synaptic plasticity thought to contribute to memory processing. METHODS: Extracellular excitatory postsynaptic potentials were recorded from the CA1 region of rat hippocampal slices. Long-term potentiation (LTP) was induced using theta-burst stimulation (10 bursts of 4 pulses at 100 Hz, applied at 5 Hz) of the Schaffer-collateral pathway, while low-frequency stimulation (1 Hz x 900 pulses) was delivered to induce long-term depression. The authors also used higher-frequency stimulation (10 bursts of 4 pulses at 200 Hz, applied at 5 Hz) in the presence of MK-801 to examine the effects of propofol on an N-methyl-D-aspartate receptor-independent form of LTP. RESULTS: At 30 microM, propofol inhibited LTP induction produced by theta-burst stimulation but had less effect on LTP maintenance. Similarly, when LTP was induced by 200-Hz stimulation in the presence of MK-801, propofol also blocked LTP induction. Propofol did not block LTP induction in the presence of picrotoxin, a specific antagonist of gamma-aminobutyric acid type A receptors, suggesting that modulation of gamma-aminobutyric acid type A receptors participates in propofol-mediated LTP inhibition. Propofol did not inhibit long-term depression. CONCLUSIONS: Propofol inhibits LTP induction through modulation of gamma-aminobutyric acid type A receptors but not via inhibition of N-methyl-D-aspartate receptors. However, other factors also possibly contribute to propofol-mediated LTP inhibition.

Anesthetics, Intravenous↗

PubMed2006

Effect of propofol anesthesia and continuous positive airway pressure on upper airway size and configuration in infants.

BACKGROUND: Infants are prone to obstruction of the upper airway during general anesthesia. Continuous positive airway pressure (CPAP) is often used to prevent or treat anesthesia-induced airway obstruction. The authors studied the interaction of propofol anesthesia and CPAP on airway caliber in infants using magnetic resonance imaging. METHODS: Nine infants undergoing elective magnetic resonance imaging of the brain were studied. Head position was standardized. Spin echo magnetic resonance images of the airway were acquired at the level of the soft palate, base of the tongue, and tip of the epiglottis. Four sets of images were acquired in sequence: (1) during light propofol anesthesia at an infusion rate of 80 microg . kg(-1) . min(-1), (2) after increasing the depth of propofol anesthesia by administering a bolus dose (2.0 mg/kg) and increasing the infusion rate to 240 microg . kg(-1) . min(-1), (3) during continued infusion of 240 microg . kg(-1). min propofol and application of 10 cm H2O CPAP, and (4) after removal of CPAP and continued infusion of 240 microg . kg(-1). min propofol. RESULTS: Increasing depth of propofol anesthesia decreased airway caliber at each anatomical level, predominantly due to anteroposterior narrowing. Application of CPAP completely reversed the propofol-induced decrease in airway caliber, primarily by increasing the transverse dimension. CONCLUSIONS: Airway narrowing with increasing depth of propofol anesthesia results predominantly from a reduction in anteroposterior dimension, whereas CPAP acts primarily to increase the transverse dimension. Although airway caliber during deep propofol anesthesia and application of CPAP was similar to that during light propofol anesthesia, there were significant configurational differences.

Anesthesia, Intravenous↗

PubMed2000

Propofol impairment of mitochondrial respiration in isolated perfused guinea pig hearts determined by reflectance spectroscopy.

OBJECTIVE: To simultaneously determine the effect of propofol on myocardial oxygenation, mitochondrial function, and whole organ function in an isolated heart model, using optical reflectance spectroscopy. DESIGN: Controlled laboratory investigation. SETTING: Research laboratory. SUBJECTS: Twenty adult guinea pigs. INTERVENTIONS: Isolated hearts were perfused alternately with a modified oxygenated Krebs-Henseleit buffer and with buffer containing varied concentrations of propofol. Ninety seconds of ischemia were produced during perfusion with each solution studied. MEASUREMENTS AND MAIN RESULTS: Myoglobin oxygen saturation, cytochrome c and cytochrome a/a3 redox state, and ventricular pressure were continuously measured from isolated guinea pig hearts during a 2-hr period. Myoglobin oxygen saturation increased and both cytochromes became more oxidized in the presence of propofol. During ischemia, myoglobin desaturation and cytochrome reduction were delayed and less complete in the presence of propofol. The mean ischemic time to 50% myoglobin desaturation was, on average, 14.3 secs with buffer perfusion, and increased to 24.5, 27.9, and 41.8 secs, with 50, 100, and 200 microM propofol perfusion, respectively. Ventricular function decreased linearly with increasing propofol concentration. From baseline buffer perfusion, maximal dP/dt per cardiac cycle decreased on average by 30.4%, 40.9%, and 69.4%, with 50, 100, and 200 microM propofol perfusion, respectively. CONCLUSIONS: Propofol impairs either oxygen utilization or inhibits electron flow along the mitochondrial electron transport chain in the guinea pig cardiomyocyte. Propofol also significantly decreases ventricular performance in the isolated perfused heart. These effects are linearly correlated with propofol concentration in the range studied.

Anesthetics, Intravenous↗

PubMed2000

Effects of propofol on hemodynamic and inflammatory responses to endotoxemia in rats.

OBJECTIVE: To document the effects of propofol on the hemodynamic and inflammatory responses to endotoxemia in an animal model. DESIGN: Randomized, prospective laboratory study. SETTING: University experimental laboratory. SUBJECTS: Thirty-two male rats. INTERVENTIONS: The animals were randomly assigned to one of four groups: a) endotoxemia group (n = 8), which received intravenous Escherichia coli endotoxin (15 mg/kg over 2 mins); b) control group (n = 8), which was treated identically to the endotoxemia group except for the substitution of 0.9% saline for endotoxin; c) propofol group (n = 8), which was treated identically to the control group but also received propofol (10 mg/kg bolus, followed by infusion at 10 mg/kg/hr) immediately after the injection of 0.9% saline; and d) propofol-endotoxemia group (n = 8), which was treated identically to the endotoxemia group with the additional administration of propofol (10 mg/kg bolus, followed by infusion at 10 mg/kg/hr) immediately after endotoxin injection. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial blood gases, and acid-base status were recorded and the blood propofol concentrations and plasma cytokine concentrations were measured during the 5-hr observation. Microscopic findings of lung tissue for each group were obtained at necropsy. The systolic arterial pressure and heart rate of the propofol-endotoxemia group were similar to those of the endotoxemia group. The increases in the plasma cytokine (tumor necrosis factor, interleukin-6, and interleukin-10) concentrations, in the base deficit, and in the infiltration of neutrophils in the air space or vessel walls of the lungs were attenuated in the propofol-endotoxemia group compared with the endotoxemia group. CONCLUSIONS: Propofol attenuated cytokine responses, base deficit, and activation of neutrophils to endotoxemia. These findings suggest that propofol may inhibit inflammatory response and prevent the development of metabolic acidosis during endotoxemia.

Animals↗

PubMedDate not supplied

Intravenous anesthesia with propofol for painful procedures in children with cancer.

OBJECTIVE: To study the safety and efficacy of propofol-based intravenous anesthesia in children with cancer undergoing painful procedures. METHODS: This study is a retrospective analysis of data collected from 52 consecutive children who underwent 335 procedures using propofol anesthesia. These data were routinely collected in all patients: time to induction, duration of the procedure, time to recover, and the doses of the drugs used. Monitoring with electrocardiography and pulse oximetry was continuous during the procedure; blood pressures were recorded before and after the procedure and every 5 to 10 minutes during the procedure. The patients received one of these four propofol-based intravenous regimens according to the anesthesiologist's preference: propofol only; propofol plus fentanyl; propofol plus midazolam; or propofol, fentanyl, and midazolam. The efficacy of sedation was rated by this scoring system: 3 = no movement during procedure; 2 = minimal movement that did not interfere with the procedure; 1 = moderate movement requiring physical restraint to complete the procedure. RESULTS: There were six episodes of mild hypoxia (oxygen saturation 85%-94%) and one episode of laryngospasm. None required intubation. Two patients had agitation and one patient had emesis during the postrecovery phase. There was no difference in the efficacy of sedation between the four regimens. Patients receiving the combination of propofol, fentanyl, and midazolam received the least amount of propofol and required the least time to recover. There were no life-threatening complications. CONCLUSIONS: Propofol-based anesthesia, when administered by an anesthesiologist in a controlled setting, is safe and effective for performing painful procedures in children with cancer.

Ambulatory Care↗

PubMed2005

Clinical variables related to propofol effect-site concentrations at recovery of consciousness after neurosurgical procedures.

Target controlled infusion (TCI) systems and computer data acquisition software are increasingly used in anesthesia. It was hypothesized that the use of such systems might allow retrieval of information useful to anticipate the effect-site concentrations of propofol at which patients would recover from anesthesia. The goal of the study was to identify variables related to propofol effect-site concentrations at recovery of consciousness (ROC). Sixteen patients with a Glasgow of 15, ASA 1 or 2, subjected to neurosurgical procedures, received TIVA with TCI propofol and remifentanil. Data were collected every 5 seconds from Datex AS3 and Aspect A200XP (BIS). Effect-site TCI was used for propofol (initial effect target 5.0 microg/ml) and for remifentanil (initial plasma target 2.5 ng/ml). All clinical events were noted. Variables possibly related to propofol effect-site concentration at ROC were selected. Data are expressed as mean +/- SD. Effect-site propofol concentration at ROC was 1.3 +/- 0.5 microg/ml. A positive correlation was found between propofol effect-site concentration at ROC and: age (49.3 +/- 17 years) (P = 0.003); mean remifentanil dose during surgery (0.11 +/- 0.05 microg/kg/min) (P = 0.003); mean propofol dose during surgery (0.12 +/- 0.03 mg/kg/min) (P = 0.046); and remifentanil effect-site concentration at ROC (2.85 +/- 2.06 ng/ml) (P = 0.002). Propofol effect-site concentrations were not correlated with: weight, height, LBM, duration of anesthesia, minimum BIS at induction (30.4 +/- 6.8), time till minimum BIS (4.7 +/- 2.2 min), mean and median BIS during surgery (38.2 +/- 4.5 and 37.8 +/- 5.3). BIS-related variables were not useful as ROC predictors. Only drug variables and age correlated with propofol effect-site concentrations at ROC.

Adult↗

PubMedDate not supplied

Short-term propofol infusion as an adjunct to extubation in burned children.

Children who require intubation as a component of their burn management generally need heavy sedation, usually with a combination of opiate and benzodiazepine infusions with a target sensorium of light sleep. When extubation approaches, the need for sedation to prevent uncontrolled extubation can conflict with the desire to lighten sedation enough to ensure that airway protective reflexes are strong. The several hours' half-life of these medications can make this period of weaning challenging. Therefore, the hours preceding extubation are among the most difficult in which to ensure safe adequate sedation. The pharmacokinetics of propofol allow for the rapid emergence of a patient from deep sedation. We have had success with an extubation strategy using short-term propofol infusions in critically ill children. In this work, children were maintained on morphine and midazolam infusions per our unit protocol, escalating doses as required to maintain comfort. Approximately 8 hours before planned extubation, these infusions were decreased by approximately half and propofol infusion added to maintain a state of light sleep. Extubation was planned approximately 8 hours later to allow ample time for the chronically infused opiates and benzodiazepines to be metabolized down to the new steady-state level. Thirty minutes before planned extubation, propofol was stopped while morphine and midazolam infusions were maintained at the reduced level. When the children awakened from the propofol-induced state of light sleep, they were extubated while the reduced infusions of morphine and midazolam were maintained. These were subsequently weaned slowly, depending on the child's need for ongoing pain and anxiety medication, per our unit protocol to minimize the incidence of withdrawal symptoms. Data are shown in the text as mean +/- standard deviation. These 11 children (eight boys and three girls) had an average age of 6.6 +/- 5.6 years (range, 1.2-13 years), average weight of 36.9 +/- 28.7 kg (range, 9.3-95 kg), and burn size of 43 +/- 21.4% (range, 10-85%). Three children had sustained scald burns and eight had flame injuries with associated inhalation injury. They had been intubated for an average of 12.7 +/- 10.9 (range, 2-33 days). Morphine infusions immediately before the initiation of propofol averaged 0.26 +/- 0.31 mg/kg/hour (range, 0.04-1.29 mg/kg/hr) and midazolam averaged 0.15 +/- 0.16 mg/kg/hr (range, 0.06-0.65 mg/kg/hr). Morphine infusions after beginning propofol and at extubation averaged 0.16 +/- 0.16 (range, 0.04-0.65 mg/kg/hr) and midazolam averaged 0.09 +/- 0.08 mg/kg/hr (range, 0.02-0.32 mg/kg/hr). Propofol doses after initial titration during the first hour of infusion averaged 3.6 +/- 2.9 mg/kg/hr (range, 0.4-8.1 mg/kg/hr). Nine of the 11 children (82%) were successfully extubated on the first attempt. Two required reintubation for postextubation stridor 2 to 6 hours after extubation but were successfully extubated the next day after a short course of steroids, again using the same propofol technique. All were awake at extubation and went on to survive. Morphine and midazolam infusions were gradually weaned, and there were no withdrawal symptoms noted. Although prolonged (days) infusions of propofol have been associated with adverse cardiovascular complications in critically ill young children and should probably be avoided, short-term (in hours) use of the drug can facilitate smooth extubation.

Adolescent↗

PubMed1997

Propofol anaesthesia and vomiting after myringoplasty in children.

To determine whether propofol anaesthesia reduces the incidence of nausea and vomiting after ear surgery, 40 children aged 4-16 years were randomly assigned to receive either propofol or inhalational anaesthesia. Children in the propofol group had anaesthesia induced with propofol and maintained with propofol-nitrous oxide and those in the inhalational group had anaesthesia induced with thiopentone and maintained with isoflurane-nitrous oxide. Nausea and vomiting were recorded for 24 h after surgery and metoclopramide was offered to children who vomited more than twice. We found that 11 children (55%) who had propofol and 14 children (70%) who had inhalational anaesthesia vomited one or more times after surgery (difference not significant). The incidence of vomiting was lower in the propofol group during the first 2 h after surgery (0% and 25% propofol and inhalational groups, respectively) (p < 0.05) but was similar at all other time intervals. Rescue anti-emetic was given to two (10%) and eight (40%) children in the propofol and inhalational groups, respectively (p < 0.05). We conclude that propofol anaesthesia alone is not an effective means of preventing vomiting after middle ear surgery in children.

Adolescent↗

PubMed1998

Effects of desflurane and propofol on arterial oxygenation during one-lung ventilation in the pig.

BACKGROUND: Desflurane depresses hypoxic pulmonary vasoconstriction (HPV) in vitro. During one-lung ventilation (OLV), HPV may reduce venous admixture and ameliorate the decrease in arterial O2 tension by diverting blood from the non-ventilated to the ventilated lung. Accordingly, this study compares the effects of desflurane with those of propofol on oxygenation during two-lung (TLV) and OLV in vivo. METHODS: Ten pigs (25-30 kg) were premedicated (flunitrazepam 0.4 mg/kg i.m.), anaesthetized (induction: propofol 2 mg/kg i.v.; maintenance: N2O/O2 50%/50%, desflurane 3%, propofol 50 micrograms kg-1 min-1, and vecuronium 0.2 mg kg-1 h-1 i.v.), orally intubated and mechanically ventilated. Femoral arterial and thermodilution pulmonary artery catheters were placed, and the orotracheal tube was replaced by a left-sided 28-Ch double-lumen tube (DLT) via tracheotomy. After DLT placement, N2O and propofol were discontinued, FiO2 was increased to 0.85, and anaesthesia continued randomly with either desflurane (1 MAC) or propofol 200 micrograms kg-1 min-1. Using a cross-over design, in each animal the effects of a), changing from TLV to OLV (left lung) during both desflurane and propofol and b), the effects of changing between the two anaesthetics during OLV were studied. RESULTS: When changing from TLV to OLV, PaO2 decreased more (p < 0.05) during desflurane (mean 75%) than during propofol (mean 60%). Changing between desflurane and propofol during OLV resulted in small but consistent (P < 0.05) increases in PaO2 (mean 15%) during propofol. CONCLUSION: Consistent with in vitro results on HPV, 1 MAC desflurane impaired in vivo oxygenation during OLV more than did propofol.

Anesthesia↗

PubMed2006

Propofol formulated with long-/medium-chain triglycerides reduces the pain of injection by target controlled infusion.

BACKGROUND: Propofol is a widely used intravenous anesthetic although its injection pain is a common and unpleasant problem. Long-/medium-chain triglyceride (LCT/MCT) propofol has been introduced, as its low free propofol content is expected to reduce injection pain compared with LCT propofol. Target controlled infusion (TCI) differs from conventional induction in the initial infusion pattern. During induction using TCI, we investigated injection pain caused by two propofol solutions with different triglyceride compositions. METHODS: Fifty patients, ASA I-II, with adequate communicative ability, were randomly assigned to two groups. TCI was conducted with Diprifusor for LCT and with BeComSim (custom-made software) for LCT/MCT. The target blood concentration was set at 4 microg/ml for both groups. At 30, 60, and 120 s after the infusion, patients were asked questions regarding the severity of pain on a 0-10 pain score. The total dose of propofol and the time required to induce anesthesia were also investigated. RESULTS: The LCT/MCT propofol group had a larger number of pain-free patients and showed lower severity of pain than the LCT group [the number of pain-free patients being 11 and 3, respectively (P < 0.05), and median maximum pain being 0 and 4.5, respectively (P < 0.01)]. The dose and time required for induction were not significantly different between the groups (dose of 84 +/- 27 and 80 +/- 24 mg, respectively, and time of 119 +/- 60 and 107 +/- 55 s, respectively). CONCLUSION: Our study showed that the frequency and severity of pain during TCI induction with propofol could be significantly reduced using LCT/MCT propofol rather than LCT propofol.

Adult↗

PubMed1998

Propofol block of cardiac sodium currents in rat isolated myocardial cells is increased at depolarized resting potentials.

1. The effect of propofol on cardiac whole-cell sodium currents and single sodium channels in rat isolated ventricular myocytes was examined using patch-clamp techniques. 2. Propofol caused a block of the whole-cell sodium current, the potency of block depending on the holding potential. When cells were held at -90 mV, the EC50 was 2.8 micrograms/mL. When cells were held more hyperpolarized (at -140 mV), the EC50 increased to 44.0 micrograms/mL. 3. Although the degree of block produced by the same concentration of propofol was different at different holding potentials, the time course of onset and recovery from block was the same. 4. The current/voltage relationship for the sodium current showed a pronounced block of peak current by propofol (40-50% block of the maximum current by 30 micrograms/mL propofol), with a minimal shift in the voltage dependence of activation and no shift in reversal potential. 5. The voltage dependence of the steady state inactivation curve was shifted to more hyperpolarized potentials by propofol (shift of 18 and 8 mV by 30 and 10 micrograms/mL propofol, respectively). 6. Single channel records showed that propofol caused a shortening of the mean channel open time (from a mean of 0.59 to 0.38 ms by 10 micrograms/mL propofol), but no change in the channel amplitude. 7. It is concluded that propofol produces a block of sodium currents in cardiac myocytes at concentrations that are comparable to those that may be attained during anaesthesia.

Anesthetics, Intravenous↗

PubMed2006

Propofol block of I(h) contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons.

Although the depressant effects of the general anesthetic propofol on thalamocortical relay neurons clearly involve gamma-aminobutyric acid (GABA)(A) receptors, other mechanisms may be involved. The hyperpolarization-activated cation current (I(h)) regulates excitability and rhythmic firing in thalamocortical relay neurons in the ventrobasal (VB) complex of the thalamus. Here we investigated the effects of propofol on I(h)-related function in vitro and in vivo. In whole-cell current-clamp recordings from VB neurons in mouse (P23-35) brain slices, propofol markedly reduced the voltage sag and low-threshold rebound excitation that are characteristic of the activation of I(h). In whole-cell voltage-clamp recordings, propofol suppressed the I(h) conductance and slowed the kinetics of activation. The block of I(h) by propofol was associated with decreased regularity and frequency of delta-oscillations in VB neurons. The principal source of the I(h) current in these neurons is the hyperpolarization-activated cyclic nucleotide-gated (HCN) type 2 channel. In human embryonic kidney (HEK)293 cells expressing recombinant mouse HCN2 channels, propofol decreased I(h) and slowed the rate of channel activation. We also investigated whether propofol might have persistent effects on thalamic excitability in the mouse. Three hours following an injection of propofol sufficient to produce loss-of-righting reflex in mice (P35), I(h) was decreased, and this was accompanied by a corresponding decrease in HCN2 and HCN4 immunoreactivity in thalamocortical neurons in vivo. These results suggest that suppression of I(h) may contribute to the inhibition of thalamocortical activity during propofol anesthesia. Longer-term effects represent a novel form of propofol-mediated regulation of I(h).

Action Potentials↗