CNS neuroscience & therapeutics
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Traditionally, the use of ketamine for patients with traumatic brain injuries is contraindicated due to the concern of increasing intracranial pressure (ICP). These concerns, however, originated from early studies and case reports that were inadequately controlled and designed. Recently, the concern of using ketamine in these patients has been challenged by a number of published studies demonstrating that the use of ketamine was safe in these patients. ⋯ Studies examining the use of ketamine for induction, maintenance, and sedation in patients with TBI have had promising results. The use of ketamine in a controlled ventilation setting and in combination with other sedative agents has demonstrated no increase in ICP. The role of ketamine as a neuroprotective agent in humans remains inconclusive and adequately powered; randomized controlled trials performed in patients undergoing surgery for traumatic brain injury are necessary.
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Status epilepticus (SE), a neurological emergency both in adults and in children, could lead to brain damage and even death if untreated. Generalized convulsive SE (GCSE) is the most common and severe form, an example of which is that induced by organophosphorus nerve agents. First- and second-line pharmacotherapies are relatively consensual, but if seizures are still not controlled, there is currently no definitive data to guide the optimal choice of therapy. ⋯ Although potentially active, ketamine has no real place for the treatment of isolated seizures, better accepted drugs being used. Its best usage should be during GCSE, but not waiting for SE to become totally refractory. Concerns about possible developmental neurotoxicity might limit its pediatric use for refractory SE.
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The old anesthetic ketamine has demonstrated interactions with the inflammatory response. This review intends to qualify the nature and the mechanism underlying this interaction. For this purpose, preclinical data will be presented starting with the initial works, and then, the probable mechanisms will be discussed. ⋯ In conclusion, ketamine appears as a unique "homeostatic regulator" of the acute inflammatory reaction and the stress-induced immune disturbances. This is of some interest at a moment when the short- and long-term deleterious consequences of inadequate inflammatory reactions are increasingly reported. Large-scale studies showing improved patient's outcome are, however, required before to definitively assert the clinical reality of this positive effect.
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For ketamine's fiftieth birthday, a narrative review of this unique drug in pain management is presented. Its history is traced from its conception, and its heritage, as a phencyclidine offspring, delineated. ⋯ The growth of the clinical evidence for perioperative pain, acute pain, and chronic pain is followed from early attempts to systematic reviews. Finally, an attempt is made to foresee what the next 50 years might hold in store for our 50 years old.
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Historical Article
Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings).
For more than 50 years, ketamine has proven to be a safe anesthetic drug with potent analgesic properties. The active enantiomer is S(+)-ketamine. Ketamine is mostly metabolized in norketamine, an active metabolite. ⋯ The consequences of high doses, repeatedly administered, are not known. Cognitive disturbances are frequent in chronic users of ketamine, as well as frontal white matter abnormalities. Animal studies suggest that neurodegeneration is a potential long-term risk of anesthetics in neonatal and young pediatric patients.