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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anesthetics appear to produce neurodepression by altering synaptic transmission and/or intrinsic neuronal excitability. Propofol, a widely used anesthetic, has proposed effects on many targets, ranging from sodium channels to GABA(A) inhibition. We examined effects of propofol on the intrinsic excitability of hippocampal CA1 neurons (primarily interneurons) recorded from adult rat brain slices. Propofol strongly depressed action potential production induced by DC injection, synaptic stimulation, or high-potassium solutions. Propofol-induced depression of intrinsic excitability was completely reversed by bicuculline and picrotoxin but was strychnine-insensitive, implicating GABA(A) but not glycine receptors. Propofol strongly enhanced inhibitory postsynaptic currents (IPSCs) and induced a tonic GABA(A)-mediated current. We pharmacologically differentiated tonic and phasic (synaptic) GABA(A)-mediated inhibition using the GABA(A) receptor antagonist SR95531 (gabazine). Gabazine (20 microM) completely blocked both evoked and spontaneous IPSCs but failed to block the propofol-induced depression of intrinsic excitability, implicating tonic, but not phasic, GABA(A) inhibition. Glutamatergic synaptic responses were not altered by propofol (< or =30 microM). Similar results were found in both interneurons and pyramidal cells and with the chemically unrelated anesthetic thiopental. These results suggest that suppression of CA1 neuron intrinsic excitability, by these anesthetics, is largely due to activation of tonic GABA(A) conductances; although other sites of action may play important roles in affecting synaptic transmission, which also can produce strong neurodepression. We propose that for some anesthetics, suppression of intrinsic excitability, mediated by tonic GABA(A) conductances, operates in conjunction with effects on synaptic transmission, mediated by other mechanisms, to depress hippocampal function during anesthesia.
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PMID:Major role for tonic GABAA conductances in anesthetic suppression of intrinsic neuronal excitability. 1514 Sep 5

This retrospective case series reports our experience using propofol for procedural sedation in the Emergency Department over an 18-month period with 52 pediatric patients. Propofol sedation was performed successfully in all children (mean age, 10.2 years; range 0.7-17.4 years). Indications for sedation included orthopedic manipulation, incision and drainage of abscess, sexual assault examination, laceration repair, and non-invasive imaging studies. The mean dose administered with the intermittent bolus and continuous infusion methods of delivery was 4.25 mg/kg (+/- 1.86) and 8.3 mg/kg/h, respectively. The mean recovery time was 27.1 min (+/- 15.84). No patient required assisted ventilation or developed clinically significant hypotension. Respiratory depression requiring airway repositioning or supplemental oxygen was noted in 5.8% (3/52) patients. Propofol is a reasonable alternative to facilitate sedation for a range of procedures performed in a busy Pediatric Emergency Department.
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PMID:Propofol for procedural sedation in the pediatric emergency department. 1521 97

The neural mechanisms of propofol-induced central respiratory depression remain poorly understood. In the present study, we studied these mechanisms and the involvement of gamma-aminobutyric acid (GABA)A receptors in propofol-induced central respiratory depression. The brainstem and the cervical spinal cord of 1- to 4-day-old rats were isolated, and preparations were maintained in vitro with oxygenated artificial cerebrospinal fluid. Rhythmic inspiratory burst activity was recorded from the C4 spinal ventral root. The activity of respiratory neurons in the ventrolateral medulla was recorded using a perforated patch-clamp technique. We found that bath-applied propofol decreased C4 inspiratory burst rate, which could be reversed by the administration of a GABAA antagonist, bicuculline. Propofol caused resting membrane potentials to hyperpolarize and suppressed the firing of action potentials in preinspiratory and expiratory neurons. In contrast, propofol had little effect on resting membrane potentials and action potential firing in inspiratory neurons. Our findings suggest that the depressive effects of propofol are, at least in part, mediated by the agonistic action of propofol on GABAA receptors. It is likely that the GABAA receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression in the newborn rat.
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PMID:A neuronal mechanism of propofol-induced central respiratory depression in newborn rats. 1528 2

Patient-maintained sedation using propofol has recently been shown to be effective for dental surgery. We compared this new technique to the established technique of operator administered midazolam. The two groups were compared before, during and after sedation. The two primary outcomes were time until discharge and oxygen saturation. Vital signs, anxiety and psychomotor skills were also compared. State anxiety was reduced to a greater extent in the propofol group (mean difference 10 (SD 4) mm; p = 0.010. Propofol patients recovered quicker (mean difference 7 (SD 1.4) min; p = 0.001). Propofol patients had a smaller reduction in arterial oxygen saturation (mean difference 0.8 (SD 0.3)%; p = 0.030), and a reduced increase in heart rate (mean difference 9 (SD 2) beats.min(-1); p < 0.001). Both techniques were well tolerated and safe. Propofol sedation offered superior anxiolysis, quicker recovery, less amnesia and less depression of simple psychomotor function.
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PMID:A partially blinded randomised controlled trial of patient-maintained propofol sedation and operator controlled midazolam sedation in third molar extractions. 1564 21

Among drugs used for the anesthesia of electroconvulsive therapy (ECT), propofol reduces seizure duration to a greater degree than etomidate. The perceived difference between the 2 anesthetics is smaller in patients with schizophrenia than in patients who suffer depression. In this study, propofol and etomidate were compared during the ECT of patients with schizophrenia, on the basis of their impact on seizure activity and on seizure-induced hemodynamic reactions. Schizophrenics (n = 34) who were treated with ECT participated in this randomized crossover study. Propofol (1 mg/kg) and etomidate (0.2 mg/kg) were used alternately. The 2 drugs were compared on the basis of EEG- and EMG-registered seizure duration, mean arterial pressure (MAP), pulse frequency, energy index, and postictal suppression. We also analyzed the number of necessary restimulations. In case of anesthesia with etomidate, both EEG- (61.29 +/- 22.4 s, 47.9 +/- 21.3 s P = 0.014) and EMG- (46.3 +/- 23.8 s, 33.6 +/- 15.9 s P = 0.006) registered seizure durations were significantly longer than in case of propofol. When using propofol, the increase in MAP was significantly lower than when etomidate was used (8.1 +/- 10.2 mm Hg, 18.3 +/- 11.2 mm Hg, P = 0.001). There were no significant differences found in the postseizure increase in pulse frequency, in postictal suppression, or in the energy index, nor did the numbers of necessary restimulations differ significantly. Propofol was found to reduce seizure duration to a significantly greater extent than etomidate. At the same time, in electrophysiological parameters that show a correlation with clinical efficacy, there was no significant difference found between the 2 anesthetics. However, the seizure-induced increase in MAP was reduced by propofol to a significantly greater degree than by etomidate.
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PMID:Etomidate versus propofol for electroconvulsive therapy in patients with schizophrenia. 1559 55

Cardiovascular, pulmonary and anaesthetic-analgesic responses were evaluated in 18 male and female dogs to determine the effect of the injectable anaesthetic propofol used in conjuction with acepromazine and butorphanol. The dogs were randomly divided into three groups. Dogs in Group A were premeditated with 0.1 mg/kg of intramuscular acepromazine followed by an induction dose of 4.4 mg/kg of intravenous propofol; Group B received 0.2 mg/kg of intramuscular butorphanol and 4.4 mg/kg of intravenous propofol; dogs in Group AB were administered a premeditation combination of 0.1 mg/kg of intramuscular acepromazine and 0.2 mg/kg of intramuscular butorphanol, followed by induction with 3.3 mg/kg of intravenous propofol. The induction dose of propofol was given over a period of 30-60 seconds to determine responses and duration of anaesthesia. Observations recorded in the dogs included heart and respiratory rates, indirect arterial blood pressures (systolic, diastolic and mean), cardiac rhythm, end-tidal CO, tension, oxygen saturation, induction time, duration of anaesthesia, recovery time and adverse reactions. The depth of anaesthesia was assessed by the response to mechanical noxious stimuli (tail clamping), the degree of muscle relaxation and the strength of reflexes. Significant respiratory depression was seen after propofol induction in both groups receiving butorphanol with or without acepromazine. The incidence of apnea was 4/6 dogs in Group B, and 5/6 dogs in Group AB. The incidence of apnea was also correlated to the rate of propofol administration. Propofol-mediated decreases in arterial blood pressure were observed in all three groups. Moderate bradycardia (minimum value > 55 beats/min) was observed in both Groups B and AB. There were no cardiac dysrhythmias noted in any of the 18 dogs. The anaesthetic duration and recovery times were longer in dogs premeditated with acepromazine/butorphanol.
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PMID:The use of propofol for induction of anaesthesia in dogs premedicated with acepromazine, butorphanol and acepromazine-butorphanol. 1603 72

Propofol (2,6-diisopropylphenol) is a widely used intravenous general anesthetic, which has been reported to produce bradycardia in patients at concentrations associated with profound sedation and loss of consciousness. Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels conduct a monovalent cationic current I(h) (also known as I(q) or I(f)) that contributes to autorhythmicity in both the brain and heart. Here we studied the effects of propofol on recombinant HCN1, HCN2, and HCN4 channels and found that the drug inhibits and slows activation of all three channels at clinically relevant concentrations. In oocyte expression studies, HCN1 channel activation was most sensitive to slowing by propofol (EC(50) values of 5.6 +/- 1.0 microM for fast component and 31.5 +/- 7.5 microM for slow component). HCN1 channels also showed a marked propofol-induced hyperpolarizing shift in the voltage dependence of activation (EC(50) of 6.7 +/- 1.0 microM) and accelerated deactivation (EC(50) of 4.5 +/- 0.9 microM). Furthermore, propofol reduced heart rate in an isolated guinea pig heart preparation over the same range of concentrations. These data suggest that propofol modulation of HCN channel gating is an important molecular mechanism that can contribute to the depression of central nervous system function and also lead to bradyarrhythmias in patients receiving propofol during surgical anesthesia.
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PMID:Impairment of hyperpolarization-activated, cyclic nucleotide-gated channel function by the intravenous general anesthetic propofol. 1603 9

Propofol (2,6-diisopropylphenol) is a short-acting intravenous anesthetic. Propofol is known to impair maintenance of long-term potentiation (LTP) in synaptic responses from Schaffer collateral-commissural (SC) pathway to CA1 pyramidal cells in the hippocampus, but the threshold concentration of propofol needed to elicit this action is unknown. The actions of propofol in vivo (e.g., amnesia, sedation, hypnosis and immobility) depend on its concentration, and thus it is necessary to determine the concentration required to impair CA1 LTP in order to assess the impact of impairment in vivo. In the present study, we investigated the effects of various concentrations of propofol on synaptic plasticity, primarily by measuring LTP at SC pathway to CA1 pyramidal cell synapses in mouse hippocampal slices. Continuous application of 50 microM propofol from 20 min before tetanus stimulation suppressed potentiation of the synaptic responses by tetanus stimulation. The suppression was pronounced from 10 min post-tetanus and about 55% suppression of the potentiation was observed at 60 min after tetanus. Propofol at 5 or 20 microM did not have this effect. The presence of gamma-aminobutyric acid type A (GABA(A)) receptors antagonist, picrotoxin, abrogated the suppression of LTP by 50 microM propofol. Propofol 50 microM did not affect long-term depression (LTD). These results suggest that the suppression of hippocampal CA1 LTP via GABA(A) receptors requires a much higher propofol concentration compared with that needed to induce amnesia.
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PMID:Propofol-mediated impairment of CA1 long-term potentiation in mouse hippocampal slices. 1611 56

Many patients in the ICU receive mechanical ventilation and require sedative medications. Anxiolysis, hypnosis, and amnesia can be considered the primary objects of sedative therapy. Intravenous benzodiazepines are the drugs most commonly used for sedation in ICU. Proper choice and use of benzodiazepines is based on knowledge of the pharmacology and is an essential component of caring for patients in the intensive care unit. Three benzodiazepines--Diazepam, Lorazepam and Midazolam--are currently available for parenteral use in the ICU. Onset and duration of action are determined by their lipid solubility. Respiratory depression and hypotension are dose-dependent. Midazolam is generally preferred to other benzodiazepines in most ICU. It has the shortest half-life of the benzodiazepines, does not have active metabolites, is water soluble and can be administered by continuous infusion. Despite the relatively short half-life of Midazolam, extensive distribution can cause prolonged sedation. Recovery time is proportional to the infusion's duration. Lorazepam is lipid soluble and dissolved in a propylene glycol carrier, produces a delayed onset and prolonged duration of effect and is preferred for long-term sedation (>48 hours). Propylene glycol toxicity is possible with high-dose or prolonged infusions. Diazepam has become less used with the introduction of the shorter-acting and less irritating benzodiazepine. The recent literature focuses on the differences between Midazolam and Propofol, the most used sedatives in ICU, their sequential use and combination. Relevant studies have been performed about propylene glycol toxicity.
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PMID:Sedation in PACU: the role of benzodiazepines. 1630 52

Sedation for short but potentially painful procedures is often undertaken in the emergency department. The ideal sedative regimen should provide analgesia and anxiolysis with minimal side effects and cardiorespiratory depression and rapid recovery post-procedure. Propofol has found increasing popularity with anaesthetists for sedation in the operating theatre. This is a review of the current literature looking at the use of propofol for procedural sedation in the emergency department. A comprehensive literature search of Medline from 1966 to week 4 of 2005, Embase from 1980 to week 10 of 2005, and the Cochrane Library was carried out using the OVID interface. Eight articles were selected for review. The evidence suggests that propofol is both effective and safe to use in the emergency department. However, several of the papers reviewed used deep levels of sedation that are not recommended in the UK by non-anaesthetists.
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PMID:A review of the use of propofol for procedural sedation in the emergency department. 1643 33


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