Study of ketamine as an obstetric anesthetic agent

Little, Brian; Chang, Tsun; Chucot, L.; Dill, Wesley A.; Enrile, L.L.; Glazko, Anthony J.; Jassani, Majida N.; Kretchmer, Henry E.; Sweet, Avron Y.

doi:10.1016/0002-9378(72)90774-0

Cited by 70 publications

(9 citation statements)

References 6 publications

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“…(R)-(-)-ketamine concentrations of 8 µM have been reported to be required for anesthesia in surgery. 65 Further, the blood concentration of ketamine racemic mixtures upon awaking was reported to range between 2.7 and 4.7 µM 66,67 and plasma concentrations between 0.17 and 0.63 µM were measured during analgesia experiments. [68][69][70] In vitro studies reported that ketamine reduced ion currents of NMDA and nAChR receptors in the same concentration range.…”

Section: Discussionmentioning

confidence: 99%

“…( R )-(−)-ketamine concentrations of 8 μM have been reported to be required for anesthesia in surgery . Further, the blood concentration of ketamine racemic mixtures upon awaking was reported to range between 2.7 and 4.7 μM , and plasma concentrations between 0.17 and 0.63 μM were measured during analgesia experiments. − In vitro studies reported that ketamine reduced ion currents of NMDA and nAChR receptors in the same concentration range. IC 50 values of 24.4−26 μM were reported for ( R )-(−)-ketamine on inhibition the NMDA receptor, while an IC 50 of 0.24 μM was found for nAChR channel blockage using racemic ketamine …”

Section: Discussionmentioning

confidence: 99%

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Membrane-Mediated Effect on Ion Channels Induced by the Anesthetic Drug Ketamine

et al. 2010

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Anesthetic drugs have been in use for over 160 years in surgery, but their mode of action remains largely unresolved. We have studied the effect of (R)-(-)-ketamine on the biophysical properties of lipid model membranes composed of palmitoyloleoylphosphatidylcholine by a combination of X-ray diffraction and all-atom molecular dynamics simulations. In agreement with several previous studies, we do not find significant changes to the membrane thickness and lateral area per lipid up to 8 mol % ketamine content. However, we observed that the insertion of ketamine within the lipid/water interface caused significant changes of lateral pressure and a pressure shift toward the center of the bilayer. The changes are predicted to be large enough to affect the opening probability of ion channels as derived for two protein models. Depending on the protein model, we found inhibition values of IC(50) = 2 mol % and 18 mol % ketamine, corresponding to approximately 0.08 and 0.9 muM concentrations in the blood circulation, respectively. This compares remarkably well with clinical applied concentrations. We thus provide evidence for a lateral pressure mediated mode of anesthesia, first proposed more than 10 years ago.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Membrane-Mediated Effect on Ion Channels Induced by the Anesthetic Drug Ketamine

et al. 2010

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“…There are numerous clinical studies of ketamine for anesthesia and procedural sedation in children and adolescents indicating its safety ( 35 – 38 ). In addition, a study of nine children inadvertently given 5–100 times the intended dose of ketamine in the emergency department showed no adverse outcomes, although prolonged sedation occurred in all cases and four experienced brief respiratory depression ( 39 ).…”

Section: Safety Of Ketaminementioning

confidence: 99%

“…Age at onset of bipolar I disorder (BPD) typically begins at 12–24 years of age. An earlier presentation of BPD-I may lead to a more severe course ( 39 ).…”

Section: Case Examplesmentioning

confidence: 99%

Ketamine-assisted psychotherapy in adolescents with multiple psychiatric diagnoses

Wolfson¹,

Andries²,

Ahlers³

et al. 2023

Front. Psychiatry

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Ketamine-assisted psychotherapy is a promising new treatment for a variety of mental disorders of adolescence. There is currently an adolescent mental health crisis, with a high prevalence of disorders, diagnostic complexity, and many adolescents failing to respond to conventional treatments. While there is strong evidence for the use of ketamine in adults for a variety of treatment-refractory mental illnesses, research in adolescents is in its early stages. Ketamine-assisted psychotherapy (KAP) has been described in adults with promising results and here we present the first published cases of the use of KAP in adolescents. The four cases include adolescents aged 14–19 at the initiation of treatment, each with a variety of comorbid diagnoses including treatment-resistant depression, bipolar disorder, eating disorders, anxiety, panic, and trauma-related symptoms. They each initially received sublingual ketamine, followed by sessions with intramuscular ketamine. Their courses varied, but each had symptomatic and functional improvements, and the treatment was well-tolerated. Subjective patient reports are included. Rapid resolution of symptomatology and suffering often occurs within months as the result of the application of KAP to adolescent psychiatric care but is not inevitable. Family involvement in the treatment process appears to be essential to success. The development of this modality may have a singularly positive impact that will expand the psychiatric toolbox and its healing potency.

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“…The dose of ketamine resulting in unresponsiveness in humans is ∼ 2 mg/kg iv, which produces plasma concentrations of 1,500-1,800 ng/ml (∼6.3-∼7.6 µM) and 2,000 ng/ml (∼8.4 µM) in adults (12)(13)(14) and children (13), respectively; consciousness reappears when the concentration falls below 1,060 ng/ml (4.5 µM) (12,14). In healthy, young (36 ± 3 yr, n = 5) human volunteers, (R,S)-ketamine (50 mg/min), (S)-ketamine (25 mg/min), or (R)-ketamine (75 mg/min) was administered over 5-7-min by continuous infusion; the infusion was discontinued after 5 min (or when no further changes were observed in the EEG over a 30-60 sec interval).…”

Section: Introductionmentioning

confidence: 99%

Targeting Affective Mood Disorders With Ketamine to Prevent Chronic Postsurgical Pain

Willis

Goldstein

2022

Front. Pain Res.

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The phencyclidine-derivative ketamine [2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one] was added to the World Health Organization's Model List of Essential Medicines in 1985 and is also on the Model List of Essential Medicines for Children due to its efficacy and safety as an intravenous anesthetic. In sub-anesthetic doses, ketamine is an effective analgesic for the treatment of acute pain (such as may occur in the perioperative setting). Additionally, ketamine may have efficacy in relieving some forms of chronic pain. In 2019, Janssen Pharmaceuticals received regulatory-approval in both the United States and Europe for use of the S-enantiomer of ketamine in adults living with treatment-resistant major depressive disorder. Pre-existing anxiety/depression and the severity of postoperative pain are risk factors for development of chronic postsurgical pain. An important question is whether short-term administration of ketamine can prevent the conversion of acute postsurgical pain to chronic postsurgical pain. Here, we have reviewed ketamine's effects on the biopsychological processes underlying pain perception and affective mood disorders, focusing on non-NMDA receptor-mediated effects, with an emphasis on results from human trials where available.

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Study of ketamine as an obstetric anesthetic agent

Cited by 70 publications

References 6 publications

Membrane-Mediated Effect on Ion Channels Induced by the Anesthetic Drug Ketamine

Membrane-Mediated Effect on Ion Channels Induced by the Anesthetic Drug Ketamine

Ketamine-assisted psychotherapy in adolescents with multiple psychiatric diagnoses

Targeting Affective Mood Disorders With Ketamine to Prevent Chronic Postsurgical Pain

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