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

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

The long QT syndrome (LQTS) is a rare, congenital or acquired disease, which may lead to fatal cardiac arrhythmias (torsade de pointes, TdP). In all LQTS subtypes, TdPs are caused by disturbances in cardiac ion channels. Diagnosis is made using clinical, anamnestic and electrocardiographic data. Triggers of TdPs are numerous and should be avoided perioperatively. Sufficient sedation and preoperative correction of electrolyte imbalances are essential. Volatile anaesthetics and antagonists of muscle relaxants should be avoided and high doses of local anaesthetics are not recommended to date. Propofol is safe for anaesthesia induction and maintenance. The acute therapy of TdPs with cardiovascular depression should be performed in accordance with the guidelines for advanced cardiac life support and includes cardioversion/defibrillation and magnesium. Torsades de pointes may be associated with bradycardia or tachycardia resulting in specific therapeutic and prophylactic measures.
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PMID:[Long QT syndrome and anaesthesia]. 1689 19

Patients with heart failure have a diminished cardiac reserve capacity that may be further compromised by anesthesia. In addition to depression of sympathetic activity, most anaesthetics interfere with cardiovascular performance, either by a direct myocardial depression or by modifying cardiovascular control mechanisms. Etomidate causes the least cardiovascular depression. It is popular for induction of anesthesia in cardiac-compromised patients; however, it is not suitable for maintenance of anesthesia because it depresses adrenocortical function. Ketamine has a favorable cardiovascular profile related to central sympathetic stimulation and inhibition of neuronal catecholamine uptake. These counteract its direct negative inotropic effect. In patients with a failing myocardium, however, the negative inotropic effects may be unmasked, resulting in deterioration in cardiac performance and cardiovascular instability. Propofol is the most popular intravenous anesthetic for maintenance of anesthesia. It does have a negative inotropic effect, but the net effect on myocardial contractility is insignificant at clinical concentrations, probably because of a simultaneous increase in the sensitivity of the myofilaments to Ca2+. Propofol protects the myocardium against ischemia-reperfusion injury, an action derived from its antioxidant and free-radical-scavenging properties as well as the related inhibition of the mitochondrial permeability transition pore. For intravenous anesthesia, propofol is always combined with an opioid. Opioids have relatively few cardiovascular side effects and, in particular, do not cause myocardial depression. Indeed, they are cardioprotective, with antiarrhythmic activity, and induce pharmacologic preconditioning of the myocardium by a mechanism similar to the inhalational anesthetics.
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PMID:Intravenous anesthesia for the patient with left ventricular dysfunction. 1670 33

Propofol-induced metabolic acidosis is well recognised in the paediatric literature, but the existence of such a syndrome in adults remains contentious. In most reported cases, metabolic acidosis complicated prolonged administration of propofol in critically ill patients. We present a case of severe non-fatal reversible metabolic acidosis, without ventilatory depression or hypoxia, related to short-term propofol infusion in an adult during and after coronary artery bypass grafting. We suggest that lactic acidosis occurred in a genetically susceptible patient with an abnormality of mitochondrial function. This report discusses an unusual adverse effect of propofol anaesthesia and sedation and highlights the need for further investigation to define propofol toxicity.
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PMID:Short-term low-dose propofol anaesthesia associated with severe metabolic acidosis. 1706 43

Propofol is a commonly used anesthetic agent, and it attenuates hypoxic ventilatory response in humans. Propofol reduce in vivo and in vitro carotid body responses to hypoxia as well as to nicotine in experimental animals. In the present study we examined the effects of propofol on carotid body responses to hypercapnia and K(+)-induced carotid body activation and compared these effects with hypoxia in an in vitro rabbit carotid body preparation. Hypoxia, hypercapnia and potassium increased the carotid sinus nerve activity and propofol attenuated the chemoreceptor responses to all three stimuli. However, the magnitude of propofol-induced attenuation was greater for hypercapnic and K(+)-induced carotid body activation compared to the hypoxic response. These observations suggest that propofol-induced attenuation of the hypoxic response is partly secondary to depression of chemoreceptor response to hypercapnia inhibiting the synergistic interactions between O(2) and CO(2) and may involve CO(2)/H(+) sensitive K(+) channels.
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PMID:Pronounced depression by propofol on carotid body response to CO2 and K+-induced carotid body activation. 1805 27

The anesthetic propofol is thought to induce rapid hypnotic sedation by facilitating a GABAergic tonic current in forebrain neurons. The depression of cardiovascular and respiratory regulation often observed during propofol suggests potential additional actions within the brainstem. Here we determined the impacts of propofol on both GABAergic and glutamatergic synaptic mechanisms in a class of solitary tract nucleus (NTS) neurons common to brainstem reflex pathways. In horizontal brainstem slices, we recorded from NTS neurons directly activated by solitary tract (ST) axons. We identified these second-order NTS neurons by time-invariant ("jitter"<200 micros), "all-or-none" glutamatergic excitatory postsynaptic currents (EPSCs) in response to shocks to the ST. In order to assess propofol actions, we measured ST-evoked, spontaneous and miniature EPSCs and inhibitory postsynaptic currents (IPSCs) during propofol exposure. Propofol prolonged miniature IPSC decay time constants by 50% above control at 1.8 microM. Low concentrations of gabazine (SR-95531) blocked phasic GABA currents. At higher concentrations, propofol (30 microM) induced a gabazine-insensitive tonic current that was blocked by picrotoxin or bicuculline. In contrast, total propofol concentrations up to 30 microM had no effect on EPSCs. Thus, propofol enhanced phasic GABA events in NTS at lower concentrations than tonic current induction, opposite to the relative sensitivity observed in forebrain regions. These data suggest that therapeutic levels of propofol facilitate phasic (synaptic) inhibitory transmission in second-order NTS neurons which likely inhibits autonomic reflex pathways during anesthesia.
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PMID:Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS). 1808 29

The hypnotic agent propofol has pharmacokinetic characteristics that allow for rapid onset and offset of drug effect and fast elimination from the body. Elderly patients show a greater sensitivity to the hypnotic effect of propofol. The drug is extensively metabolized in the liver through the cytochrome P450 system and glucuronidation, with potential for drug interaction. Propofol does not cause significant inotropic depression at clinically relevant concentrations. But in vitro, propofol impairs isotonic relaxation of the heart and decreases free cytosolic Ca(2+) concentrations in myocardial cells. In animal models, the cardioprotective effects of propofol derive in part from its antioxidant and free radical scavenging properties. Propofol decreases cerebral blood flow and cerebral metabolic rate dose-dependently. The neuroprotective effect of propofol in animal models is attributed to its antioxidant property, the potentiation of gamma-aminobutyric acid type A (GABA(A))-mediated inhibition of synaptic transmission, and the inhibition of glutamate release. Subhypnotic doses of propofol induce sedative, amnestic, and anxiolytic effects in a dose-dependent fashion. Propofol impairs ventilation with a considerable effect on the control of ventilation and central chemoreceptor sensitivity. Propofol reduces the ventilatory response to hypercapnia and the ventilatory adaptation to hypoxia, even at subanesthetic doses. The drug potentiates hypoxic pulmonary vasoconstriction, an effect caused by inhibition of K(+) (ATP)-mediated pulmonary vasodilatation. Most of the pharmacological actions of propofol result from interaction with the GABA(A) receptor or with calcium channels. Propofol prolongs inhibitory postsynaptic currents mediated by GABA(A) receptors, indicating that its effects are associated with enhanced inhibitory synaptic transmission, but propofol also influences presynaptic mechanisms of GABAergic transmission. Propofol modulates various aspects of the host's inflammatory response. It decreases secretion of proinflammatory cytokines, alters the expression of nitric oxide, impairs monocyte and neutrophil functions, and has potent, dose-dependent radical scavenging activity similar to the endogenous antioxidant vitamin E.
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PMID:Propofol. 1817 94

Propofol (2,6-diisopropylphenol) is a versatile, short-acting, intravenous (i.v.) sedative-hypnotic agent initially marketed as an anesthetic, and now also widely used for the sedation of patients in the intensive care unit (ICU). At the room temperature propofol is an oil and is insoluble in water. It has a remarkable safety profile. Its most common side effects are dose-dependent hypotension and cardiorespiratory depression. Propofol is a global central nervous system (CNS) depressant. It activates gamma-aminobutyric acid (GABA A) receptors directly, inhibits the N-methyl-d-aspartate (NMDA) receptor and modulates calcium influx through slow calcium-ion channels. Furthermore, at doses that do not produce sedation, propofol has an anxiolytic effect. It has also immunomodulatory activity, and may, therefore, diminish the systemic inflammatory response believed to be responsible for organ dysfunction. Propofol has been reported to have neuroprotective effects. It reduces cerebral blood flow and intracranial pressure (ICP), is a potent antioxidant, and has anti-inflammatory properties. Laboratory investigations revealed that it might also protect brain from ischemic injury. Propofol formulations contain either disodium edetate (EDTA) or sodium metabisulfite, which have antibacterial and antifungal properties. EDTA is also a chelator of divalent ions such as calcium, magnesium, and zinc. Recently, EDTA has been reported to exert a neuroprotective effect itself by chelating surplus intracerebral zinc in an ischemia model. This article reviews the neuroprotective effects of propofol and its mechanism of action.
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PMID:The experimental and clinical pharmacology of propofol, an anesthetic agent with neuroprotective properties. 1848 23

Propofol, an intravenous general anaesthetic, exerts anaesthetic actions through interaction with gamma-aminobutyric acid type A (GABA(A)) receptors in the supraspinal nervous system. However, whether propofol has any significant effects on synaptic transmission at the spinal level and whether it exhibits antinociceptive action is still not fully clarified. Spontaneous activity and stimulus-evoked responses of substantia gelatinosa (SG) neurones to noxious pinch stimuli were recorded using spontaneously breathing rats under propofol anaesthesia using in vivo whole-cell patch-clamp techniques. Precise actions of propofol on GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs) as well as excitatory postsynaptic currents (EPSCs) in SG neurones were also analyzed in spinal cord slice preparations. At clinical doses (5 mg/kg), propofol reversibly depressed action potentials elicited by noxious mechanical stimuli applied to the skin in the majority (6/8) of SG neurons recorded under in vivo conditions. This depression may have been caused by interactions of propofol with GABA(A) receptors, as decay time of GABAergic sIPSCs was prolonged after propofol injection (128 +/- 11% of control, n = 5) with minimal effect on EPSCs. Although prolongation of IPSCs in vivo was reversible, IPSCs were progressively prolonged even after washout of propofol when the effect was tested using spinal cord slices. Propofol had a mild depressant effect on Adelta- and C-afferent-mediated EPSCs. We conclude that systemic bolus injection of propofol reversibly depressed nociceptive transmission, at least in part, by enhancing postsynaptic GABA(A) receptor-mediated responses in the SG.
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PMID:Actions of propofol on substantia gelatinosa neurones in rat spinal cord revealed by in vitro and in vivo patch-clamp recordings. 1922 60


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