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:10.1097/00132586-197304000-00051

Cited by 16 publications

(26 citation statements)

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“…Ketamine produces an anaesthetic state at concentrations from 2.7 ± 4.7 mM (Little et al, 1972;Idvall et al, 1979). Whereas, analgesia occurs at lower ketamine concentrations (Grant & Lovinger, 1995).…”

Section: Discussionmentioning

confidence: 99%

Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant α7 and α4β2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes

Coates

Flood

2001

British J Pharmacology

107

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1 Ketamine is a dissociative anaesthetic that is formulated as Ketalar, which contains the preservative benzethonium chloride (BCl). We have studied the e ects of pure racemic ketamine, the preservative BCl and the Ketalar mixture on human neuronal nicotinic acetylcholine receptors (nAChRs) composed of the a7 subunit or a4 and b2 subunits expressed in Xenopus laevis oocytes. 2 Ketamine inhibited responses to 1 mM acetylcholine (ACh) in both the human a7 and a4b2 nAChRs, with IC 50 values of 20 and 50 mM respectively. Inhibition of the a7 nAChRs occurred within a clinically relevant concentration range, while inhibition of the a4b2 nAChR was observed only at higher concentrations. The Ketalar formulation inhibited nAChR function more e ectively than was expected given its ketamine concentration. The surprising increased inhibitory potency of Ketalar compared with pure ketamine appeared to be due to the activity of BCl, which inhibited both a7 (IC 50 value of 122 nM) and a4b2 (IC 50 value of 49 nM) nAChRs at concentrations present in the clinical formulation of Ketalar. 3 Ketamine is a noncompetitive inhibitor at both the a7 and a4b2 nAChR. In contrast, BCl causes a parallel shift in the ACh dose-response curve at the a7 nAChR suggesting competitive inhibition. Ketamine causes both voltage-dependent and use-dependent inhibition, only in the a4b2 nAChR. 4 Since a7 nAChRs are likely to be inhibited during clinical use of Ketalar, the actions of ketamine and BCl on this receptor subtype may play a role in the profound analgesia, amnesia, immobility and/or autonomic modulation produced by this anaesthetic. British Journal of Pharmacology (2001) 134, 871 ± 879 Keywords: Neuronal nicotinic acetylcholine receptors; benzethonium chloride; ketamine; anaesthetic mechanism Abbreviations: BCl, benzethonium chloride; nAChRs, neuronal nicotinic acetylcholine receptors IntroductionKetamine is a dissociative anaesthetic, that is an e ective analgesic, amnestic and hypnotic, but causes hallucinations that limit its usefulness as a clinical anaesthetic agent. Due to its potency as an analgesic and its sympathomimetic properties, ketamine ®nds extensive use in the treatment of burn patients in intensive care settings. In the early 1980's Lodge described ketamine as a selective inhibitor of NMDA receptor activity and neuronal nicotinic receptors (nAChRs) on Renshaw cells of the cat spinal cord (Anis et al., 1983). Ketamine is also an antagonist of NMDA receptors in rat cortex (Harrison & Simmonds, 1985) and blocks these receptors at sub-clinical concentrations, by acting both as a use-dependent open channel blocker (Honey et al., 1985) and through allosteric inhibition (Orser et al., 1997). Ketamine inhibits the response to acetylcholine or nicotine in both muscle and neuronal type nAChRs (Sumikawa et al., 1983;Wachtel & Wegrzynowicz, 1992;Scheller et al., 1996;Durieux, 1995;Furuya et al., 1999;Flood & Krasowski, 2000;Friederich et al., 2000;Sasaki et al., 2000;Yamakura et al., 2000). In the case of nAChRs containing the a4 subunit, ...

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Section: Discussionmentioning

confidence: 99%

Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant α7 and α4β2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes

Coates

Flood

2001

British J Pharmacology

107

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“…One study of ketamine as an obstetric analgesic by Little et al [3] observed an increase in uterine tone. Others [4,5] have shown that ketamine causes uterine stimula tion, but none of them has correlated these findings with the effect on the decreased du ration of the second stage of labour reported here.…”

Section: Discussionmentioning

confidence: 99%

“…Keta mine hydrochloride was chosen for this study because of its rapid onset of action, profound analgesia, wide margin of safety, minimal depression of laryngeal and pharyn geal reflexes, low incidence of vomiting and minimal depression of respiratory and car diovascular function. It does not prolong la bour and is rapidly metabolized resulting in the relatively rapid recovery of the patient [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Low-Dose Ketamine Infusion as an Analgesic for Vaginal Delivery

Youssef

Shafi

Alfy

1990

Med Principles Pract

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Ketamine hydrochloride in low-dose infusion was used as an analgesic drug for 44 mothers who underwent normal vaginal delivery. The mean initial dose required was 30.0 mg (SD 10.5), and the mean maintenance dose given was 22.5 µg/kg/min (SD 8.6). Good analgesia, increased uterine activity and an insignificant decrease in the duration of the second stage of labour were noted. Fetal welfare was unimpaired as judged by the high Apgar score at 1 and 5 min after birth and the excellent neurobehavioural status. The main side effects recorded were a significant increase in arterial blood pressure and pulse rate. Vivid dreams, none of which were unpleasant, were reported by 4 mothers (18%) in the group given ketamine alone as compared to 3 mothers (13.6%) in the control group and 1 mother (4.5%) in the group given ketamine followed by midazolam 5 mg. This study showed that low-dose ketamine infusion during normal vaginal delivery in uncomplicated cases is a satisfactory method of analgesia that is safe for both the mother and the newborn infant.

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“…O uso da cetamina em anestesia para cesarianas pode resultar em hipertensão arterial e taquicardia, o que a torna inadequada para pacientes com pré-eclâmpsia ou eclâmpsia. Essa droga pode ser um bom agente para a indução da anestesia, especialmente nas pacientes hipovolêmicas, não comprometendo o feto, desde que não sejam utilizadas doses acima de 1,5 mg.kg -1 43,44 . CONCLUSÃO Apesar dos progressos importantes alcançados nessa área de conhecimento, muitas dúvidas permanecem ainda com relação ao uso de drogas durante o período de gestação.…”

Section: Drogas Anestésicas E Efeitos Fetaisunclassified

“…Ketamine in cesarean section anesthesia may result in hypertension and tachycardia, making it inadequate for pre-eclampsia or eclampsia patients 2 . The drug may be a good agent for anesthesia induction, especially in hypovolemic patients and does not affect the fetus if doses does not exceed 1.5 mg.kg -1 43,44 . CONCLUSION Important progresses were achieved in this area of knowledge, but there are still many issues about the use of drugs during gestation.…”

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confidence: 99%