Effect Of Anesthetic Propofol Research Articles

Multi-drug therapy for epilepsy influenced bispectral index after a bolus propofol administration without affecting propofol\u2019s pharmacokinetics: a prospective cohort study

Some previous studies have indicated that valproate (VPA) might change the pharmacokinetics and enhance the effects of propofol. We evaluated whether clinical VPA therapy affected the propofol blood level, the protein-unbound free propofol level, and/or the anesthetic effects of propofol in the clinical setting. The subjects were divided into the control group (not medicated with antiepileptics), the mono-VPA group (medicated with VPA alone), and the poly-VPA group (medicated with VPA, other antiepileptics, and/or psychoactive drugs). General anesthesia was induced via the administration of a single bolus of propofol and a remifentanil infusion, and when the bispectral index (BIS) exceeded 60 sevoflurane was started. There were no significant differences in the total blood propofol level at 5, 10, 15, and 20 min or the protein-unbound free propofol level at 5 min after the intravenous administration of propofol between the 3 groups. However, the minimum BIS was significantly lower and the time until the BIS exceeded 60 was significantly longer in the poly-VPA group. In the multivariate regression analysis, belonging to the poly-VPA group was found to be independently associated with the minimum BIS value and the time until the BIS exceeded 60. Clinical VPA therapy did not influence the pharmacokinetics of propofol. However, multi-drug therapy involving VPA might enhance the anesthetic effects of propofol.

The anesthetic effect of propofol or etomidate in geriatric dogs premedicated with butorphanol and diazepam

The anesthetic effect of propofol or etomidate in geriatric dogs premedicated with butorphanol and diazepam

Propofol Anesthesia Is Reduced in Phospholipase C-Related Inactive Protein Type-1 Knockout Mice.

The GABA type A receptor (GABAA-R) is a major target of intravenous anesthetics. Phospholipase C-related inactive protein type-1 (PRIP-1) is important in GABAA-R phosphorylation and membrane trafficking. In this study, we investigated the role of PRIP-1 in general anesthetic action. The anesthetic effects of propofol, etomidate, and pentobarbital were evaluated in wild-type and PRIP-1 knockout (PRIP-1 KO) mice by measuring the latency and duration of loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR). The effect of pretreatment with okadaic acid (OA), a protein phosphatase 1/2A inhibitor, on propofol- and etomidate-induced LORR was also examined. PRIP-1 deficiency provided the reduction of LORR and LTWR induced by propofol but not by etomidate or pentobarbital, indicating that PRIP-1 could determine the potency of the anesthetic action of propofol. Pretreatment with OA recovered the anesthetic potency induced by propofol in PRIP-1 KO mice. OA injection enhanced phosphorylation of cortical the GABAA-R β3 subunit in PRIP-1 KO mice. These results suggest that PRIP-1-mediated GABAA-R β3 subunit phosphorylation might be involved in the general anesthetic action induced by propofol but not by etomidate or pentobarbital.

Domains of the brain which propofol acts on, an update

Background Propofol is one of the most common intravenous general anesthetics used in current clinical practices. The anesthetic mechanism of propofol, particularly the functional targets of propofol within the brain, has not yet been fully clarified. Objective To discuss which domains may be the target locations of propofol in the brain. Content To expound the possible correlation between the anesthetic mechanism of propofol and endogenous sleep hypothalamic pathway, ascending reticular activating system, thalamic cortical network or thalamic reticular nucleus. Trend To reveal the initial nuclei or related area in the brain of the anesthetic effect of propofol will possess important guiding significance for avoiding the adverse consequences of much deep or much light anesthesia, reducing the complications of anesthesia and developing more effective anesthetic drugs. Key words: Propofol; Anesthetic mechanism; Brain

Intralipid Reverses Propofol‐Mediated Hypotension in Rats

IntroductionPropofol is a commonly used anesthetic. Despite its favourable safety profile, propofol causes hypotension which can result in end‐organ hypoperfusion. Intralipid is a lipid emulsion that has been shown to reverse the vasodilatory effects of propofol in isolated vessels; however, whether these effects are recapitulated in vivo is not known. The objectives of this study were to determine if intralipid reverses the hypotensive and anesthetic effects of propofol in rats.MethodsUnder isoflurane anesthesia, male Sprague Dawley rats were instrumented with indwelling catheters for mean arterial pressure (MAP) assessments as well as subdural electrodes for cortical activity assessments by electroencephalography (EEG).ResultsPropofol (10 mg/kg IV) caused hypotension (55±2% drop in MAP, P<0.001) and intralipid (4mL/kg IV) caused greater reversal (80±9%) of blood pressures compared to saline (19±1%; P<0.001). Blockade of the autonomic nervous system with chlorisondamine (2.5 mg/kg IV) caused marked hypotension (56±3% lowering of MAP, P<0.001) which could be reversed with a constant infusion of phenylephrine (300 μg/kg/hr); under these conditions, propofol nevertheless caused hypotension (12±4% lowering of MAP) which was completely reversed by intralipid. Propofol‐induced cortical burst suppression was not affected by intralipid (2±3%), saline (‐4%) or 20% BSA (‐2±1%; P=0.27).ConclusionThese results demonstrate that intralipid reverses propofol‐mediated hypotension with minimal effects on its anesthetic profile. Intralipid could be particularly useful as a rescue against propofol in patients prone to hemodynamic instability such as the elderly.This work was funded by a grant from the University Hospital Foundation.

Anesthetic effects of propofol in the healthy human brain: functional imaging evidence.

Functional imaging methods, including positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), have become important tools for studying how anesthetic drugs act in the human brain to induce the state of general anesthesia. Recent imaging studies using fMRI and PET techniques have demonstrated the regional effects of propofol on the brain. However, the pharmacological mechanism of the action of propofol in the intact human central nervous system is unclear. To explore the possible action targets of propofol in the human brain, a systematic review of the literature was performed. The literature search was performed with limiting factors of "propofol," "functional imaging," "positron emission tomography", and "functional magnetic resonance imaging" from 1966 to July 2013 (using Medline, EMBASE, CINAHL and hand searches of references). Studies meeting the inclusion criteria were reviewed and critiqued for the purpose of this literature research. Eighteen researches meeting the inclusion criteria were reviewed in terms of the appropriateness of valuation technique. In the unconscious state, propofol sharply reduces the regional glucose metabolism rate (rGMR) and regional cerebral blood flow (rCBF) in all brain regions, particularly in the thalamus. However, GMR, such as in the occipital, temporal, and frontal lobes, was obviously decreased at a sedative dosage of propofol, whereas, changes in the thalamus were not obvious. Using fMRI, several studies observed a decrease of connectivity of the thalamus versus an increase of connectivity within the pons of the brainstem during propofol-induced mild sedation. During deep sedation, propofol preserves cortical sensory reactivity, the specific thalamocortical network is moderately affected, whereas the nonspecific thalamocortical network is severely suppressed. In contrast, several recent fMRI studies are consistent on the systemic decreased effects of propofol in the frontoparietal network. Accumulating evidence suggest that propofol-induced unconsciousness is associated with a global metabolic and vascular depression in the human brain and especially with a significant reduction in the thalamocortical network and the frontoparietal network.

Role of intercellular gap junction in propofol and sevoflurane anesthesia in rats

Objective To evaluate the role of intercellular gap junction in the propofol and sevoflurane anesthesia in rats. Methods Eighty male Wistar rats weighing 210-260 g were randomly divided into 8 groups (n = 10 each): control group (group C), carbenoxolone group (group CA), propofol group (group P), different doses of carbenoxolone + propofol groups (groups CA1 + P, CA2 + P, CA3 + P), sevoflurane group (group S) and carbenoxolone + sevoflurane group (group CA + S). The animals ware anesthetized with intraperitoneal 10% chloraldurate 4 mg/kg and placed in a stereotactic apparatus to locate the lateral ventricle. In group C, after normal saline (NS) 2 μl was injected into the latersl ventricle, intraperitoneal NS 2 ml was injected. In group CA, after carbenoxolone 200 μg was injected into the lateral ventricle, intraperitoneal NS 2 ml was injected. In groups P,CA1 + P, CA2 + P and CA3 + P, NS 2 μl, and carbenoxolone 200, 300 and 400 μg were injected into the lateral ventricle respectively and then propofol 5 mg/100 g was injected intraperitoneally. Group S inhaled 1% sevoflurane (in increments of 0. 1% ) until the righting reflex was lost. Group CA + S inhaled 1% sevoflurane (in increments of 0.1% ) until the righting reflex was lost after carbenoxolono 200 μg was injected into the lateral ventricle. The time of loss of righting reflex, duration of loss of righting reflex and the sevoflurane concentration when the righting reflex disappeared were recorded. Results The loss of righting reflex did not appear in groups C and CA. Compared with group P, the time of loss of righting reflex was significantly shortened and duration of loss of righting reflex prolonged in groups CA1 + P, CA2 + P, CA3 + P ( P ＜ 0.01 ). The time of loss of righting reflex was significandy shorter in groups CA2 + P, CA3 + P than in group CA1 + P (P ＜ 0.05). The sevoflurane concentration when the righting reflex disappeared was significantly lower in group CA + S than in group S ( P ＜ 0.05 ). There was no significant difference in the time of loss of righting reflex and duration of loss of righting reflex between CA + S and S groups ( P ＞ 0.05). Conclusion Although inhibition of the function of gap junction can strengthen the anesthetic effects of propofol and sevoflurane, it is not the major mechanism. Key words: Cell communication ; Propofol; Anesthesia ; Sevoflurane

Pharmacokinetic and Pharmacodynamic Interactions of Ethanol and Propofol in Rabbits

Propofol is a short-acting intravenous anesthetic which is rapidly metabolized by glucuronidation and ring hydroxylation catalyzed by cytochrome P450. In clinical trials, it was found that patients receiving both ethanol and propofol injection in the surgery awoke significantly earlier than those who were injected propofol alone. To investigate pharmacokinetic and pharmacodynamic interactions of propofol and ethanol, propofol was injected alone and in combination with ethanol to rabbits. Propofol was injected intravenously at a dose rate of 15 mg kg−1. Ethanol was injected intraperitoneally at a dose rate of 2.5 mg kg−1. An LC assay with native fluorescence detection was developed and validated for determining the concentration of propofol in rabbit plasma and the effect of co-injected ethanol on the plasma pharmacokinetics of propofol in rabbits. Co-injection of ethanol decreased the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC0–∞) of propofol by 53.28 and 53.42%, respectively, as compared to the control (P < 0.001). Concomitant ethanol also caused a 66.67% increase in plasma clearance (CL) (P < 0.001). These may partially explain the finding that co-injected ethanol reduced the anesthetic effect of propofol by introducing hepatic microsomal drug-metabolizing enzymes activity in rabbits.

Effects of anesthetic propofol on release of amino acids from the spinal cord during visceral pain

As one of general anesthetics, propofol, has been used for surgical procedures of visceral organs. However, the mechanisms underlying the action of propofol on visceral nociception remain controversial. The aim of this study is to test whether the antinociception of systemic administration of propofol against visceral stimuli is related to the changes in release of excitatory and inhibitory amino acids in the spinal cord. The spinal microdialysis catheters were implanted subarachnoidally via the atlanto-occipital membrane in healthy SD rats. The rats received an intraperitoneal injection of acetic acid for visceral pain induction 10 min after intraperitoneal pretreatment with vehicle or propofol (100 mg/kg). The acetic acid-induced writhing assay was used to determine the degree of antinociception. Cerebrospinal fluid dialysate was collected by microdialysis from the spinal subarachnoid space before pretreatment and after visceral pain induction. Visceral pain-induced release of amino acids into the dialysate, including glutamate, aspartate, and γ-amino butyric acid was evaluated by measuring the changes in the concentrations of these amino acids. Acetic acid increased release of aspartate and glutamate, and decreased release of γ-amino butyric acid in the cerebrospinal fluid as measured by microdialysis. Pretreatment with propofol significantly decreased writhing responses induced by visceral pain, suppressed the visceral pain-induced aspartate and glutamate release, and reversed the decreased release of γ-amino butyric acid in the cerebrospinal fluid. These data provide evidence for a potential mechanism for the antinociceptive effects of propofol on visceral nociception.

Effect of propofol on interhemispheric EEG cross-approximate entropy in rats

Objective To investigate the effect of propofol on interhemispheric EEG cross-approximate entropy (C-ApEn) in rats. Methods Thirty-six male SD rats weighing 300-350 g were randomly divided into 3 groups (n = 12 each). Pairs of epidural electrodes were implanted in the corresponding areas in the parietal,frontal and occipital cortices respectively. The infusion rate of propoful was started at 400 μg·kg-1·min-1 and increased in 100 μg·kg-1·min-1 increments every 10 min until 900 μg·kg-1·min-1 . The rats were breathing spontaneously, Interhcmispheric EEG C-ApEn of different cortices at different doses were calculated and compared. Loss of rigting reflex and tail-clamping reflex as a function of anesthetic concentration of propofol was tested a week before the epidural electrodes were placed. Results Interhemispheric EEG C-ApEn of the parietal, frontal and occipital cortices decreased dose-dependently as propofol concentration increased. Interhemispheric righting and tail clamping reflex. Conclusion Propofol decreases the information exchange and connection of the parietal, frontal and occipital cortices in the bilateral hemisphere dose-dependently. C-ApEn is a sensitive non-linear EEG parameter correlated with different anesthetic effects of propofol. Key words: Electroencephalography; Propofol; Nonlinear dynamics; Entropy

Propofol-induced Dyskinesias Controlled with Dexmedetomidine during Deep Brain Stimulation Surgery

for the next 5 min. At this point, 1.5 g/kg dexmedetomidine was administered as a loading dose over 20 min. The patient’s dyskinesias subsided within 18 –20 min of dexmedetomidine infusion. The dexmedetomidine infusion rate was then reduced to 1.2 g kg 1 h 1 for another 10 min, after which it was continued at a rate of 0.2– 0.5 g kg 1 h 1 . When the infusion was stopped just before the microelectrode recordings, dyskinesias recurred. The dexmedetomidine infusion was restarted with good control of dyskinetic movements and titrated to keep the patient sufficiently awake to answer questions. Specifically, during microstimulation at the end of microelectrode recording for each tract, the patient was asked whether he experienced paresthesias or pulling in the muscles of his face, arms, or legs. During macrostimulation at the time of placement of the DBS electrodes, he was asked to move his fingers or toes. This allowed satisfactory placement of bilateral subthalamic nucleus DBS electrodes. Approximately an hour after surgery, the patient had another brief episode of dyskinesias that subsided spontaneously while he was in the postoperative care unit. The patient was off dexmedetomidine infusion at this time. The patient did well postoperatively and was discharged home without further problems. During his follow-up visit at 5 weeks, he reported improvement of all symptoms, indicating satisfactory DBS function.

β3-Containing Gamma-Aminobutyric AcidA Receptors Are Not Major Targets for the Amnesic and Immobilizing Actions of Isoflurane

Mice bearing an N265M point mutation in the gamma-aminobutyric acid (GABA)(A) receptor beta3 subunit resist various anesthetic effects of propofol and etomidate. They also require a 16% larger concentration of enflurane and a 21% larger concentration of halothane to abolish the withdrawal reflex than do wild-type mice. Using a Pavlovian test, we measured whether this mutation increased the concentration of isoflurane required to impair learning and memory relative to wild-type mice. We found that the concentration was not significantly increased. We also measured MAC (the minimum alveolar concentration required to eliminate movement in response to noxious stimulation in 50% of subjects). Isoflurane MAC for mutant mice (1.93% +/- 0.0.03%; mean +/- se; n = 14) was 17.0% larger than MAC for wild-type mice (1.65 +/- 0.04; n = 14; P < 0.001). Similarly, the cyclopropane MAC for mutant mice (27.6% +/- 0.55%; n = 16) was 13.6% larger than MAC for wild-type mice (24.3 +/- 0.46; n = 8; P < 0.01). The increase in MAC for cyclopropane was unexpected, because published reports find only minimal actions at alpha1beta2gamma2 GABA(A) receptors whereas isoflurane provides a large enhancement. Consistent with previous work on alpha1beta2gamma2 GABA(A) receptors, we found in Xenopus oocytes that 5 MAC cyclopropane enhanced the effect of GABA on alpha1beta2gamma2 GABA(A) receptors by only 76%, and by a nearly identical enhancement in alpha1beta3gamma2, and alpha6beta3gamma2 receptors. In contrast, a much smaller concentration of isoflurane (1 MAC) produced a 160% to 310% enhancement in these receptors. If, relative to isoflurane, cyclopropane minimally increases GABA-induced chloride currents at any GABA(A) receptor subtype, the present data for MAC are consistent with the notion that GABA(A) receptors do not mediate the immobility produced by inhaled anesthetics. The results of the present study indicate that beta3-containing gamma-aminobutyric acidA receptors do not mediate the amnesia produced by isoflurane and do not mediate, or only partially mediate, the immobility produced by inhaled anesthetics.

Cardiorespiratory and anesthetic effects of propofol and thiopental in dogs

Abstract Objective To compare cardiorespiratory and anesthesia effects of IV administered propofol and thiopental in dogs. Animals 6 healthy mixed-breed dogs. Procedure Each dog was anesthetized with isoflurane, then a thermistor catheter was inserted in the pulmonary artery. After a minimum of 2.5 hours of recovery, a catheter was placed in a cephalic vein for administration of lactated Ringer's solution and drugs. Propofol (8 mg/kg of body weight) or thiopental (19.4 mg/kg) was administered to each dog in a randomized crossover design study. All dogs were intubated and allowed to breathe 100% oxygen spontaneously. Heart rate and rhythm; systolic, diastolic, and mean arterial blood pressures; respiratory rate; end-tidal carbon dioxide concentration; tidal volume; and reflexes (toe web pinch, palpebral response, and jaw tone) were measured before and every 2 minutes for the first 10 minutes, then at 15, 30, and 60 minutes after drug administration. Cardiac output was determined at 0, 2, 6, 10, 15, 30, and 60 minutes, and blood samples were collected at 0, 2, 10, and 30 minutes. Time to endotracheal extubation, head lift, and ability to sit sternally and walk unaided were recorded. Results 3 of 6 dogs in each group were apneic after drug administration. Reflexes were decreased similarly for both anesthetic agents, but were not completely lost. Time to sternal position and walking unaided were significantly shorter in response to propofol. Conclusion Anesthesia was rapid; however, respiratory depression and apnea were major adverse effects associated with propofol and thiopental. Propofol has the advantage of inducing rapid, coordinated anesthesia recovery. (Am J Vet Res 1998;59:1137-1143)

Cardiopulmonary and anesthetic effects of propofol in wild turkeys

Abstract Objective To determine safety, anesthetic variables, and cardiopulmonary effects of IV infusion of propofol for induction and maintenance of anesthesia in wild turkeys. Animals 10 healthy, adult wild turkeys. Procedure Anesthesia was induced by IV administration of propofol (5 mg/kg of body weight) over 20 seconds and was maintained for 30 minutes by constant IV infusion of propofol at a rate of 0.5 mg/kg/min. Heart and respiratory rates, arterial blood pressures, and arterial blood gas tensions were obtained prior to propofol administration (baseline values) and again at 1, 2, 3, 4, 5, 10, 15, 20, 25, and 30 minutes after induction of anesthesia. All birds were intubated immediately after induction of anesthesia, and end-tidal CO2 concentration was determined at the same time intervals. Supplemental oxygen was not provided. Results Apnea was observed for 10 to 30 seconds after propofol administration, which induced a decrease in heart rate; however, the changes were not significant. Compared with baseline values, respiratory rate was significantly decreased at 4 minutes after administration of propofol and thereafter. Systolic, mean, and diastolic pressures decreased over the infusion period, but the changes were not significant. Mean arterial blood pressure decreased by 30% after 15 minutes of anesthesia; end-tidal CO2 concentration increased from baseline values after 30 minutes; PO2 was significantly decreased at 5 minutes after induction and thereafter; PCO2 was significantly (P&lt; 0.05) increased after 15 minutes of anesthesia; and arterial oxygen saturation was significantly (P &lt; 0.05) decreased at the end of anesthesia. Two male turkeys developed severe transient hypoxemia, 1 at 5 and the other at 15 minutes after induction. Time to standing after discontinuation of propofol infusion was 11 ± 6 minutes. Recovery was smooth and unremarkable. Conclusion Propofol is an effective agent for IV induction and maintenance of anesthesia in wild turkeys, and is useful for short procedures or where the use of inhalational agents is contraindicated. (Am J Vet Res 1997;58:1014–1017)