Transplacental Passage of Ketamine after Intravenous Administration

Ellingson, A.; Haram, Kjell; Sagen, Norvald; Solheim, Eirik

doi:10.1111/j.1399-6576.1977.tb01191.x

Cited by 50 publications

(16 citation statements)

References 6 publications

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“…respiratory depression. [60] 3.1.5 Opioids usually administered after delivery of the fetus to maintain muscle Occasionally, high doses of opioids are used to induce general relaxation after the effects of suxamethonium chloride wear off. In anesthesia.…”

Section: Ketaminementioning

confidence: 99%

Effects of Obstetric Analgesics and Anesthetics on the Neonate

2003

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Most anesthetic and analgesic agents in current use traverse the placental barrier in varying degrees, but are well tolerated by the fetus if judiciously administered. For labor analgesia, many options are available. Systemic administration of opioids and sedatives is one such option. Repeated maternal administration of opioids such as pethidine (meperidine) results in significant fetal exposure and neonatal respiratory depression. Patient-controlled analgesia with synthetic opioids such as fentanyl, alfentanil, and the new ultra-short-acting remifentanil may be used for labor analgesia in selected patients. Other options for labor analgesia include epidural and combined spinal-epidural techniques. With such techniques, neonatal exposure to opioids and sedatives can be minimized or totally avoided. While limiting the fetal exposure to the harmful effects of depressant drugs, epidural anesthesia and/or analgesia improves placental perfusion and oxygenation of the fetus, which is beneficial, especially in conditions such as pregnancy-induced hypertension. Regional blocks are also administered for the majority of cesarean deliveries because of the overwhelming and unequivocal evidence of maternal and fetal safety compared with general anesthesia for this indication. However, in some instances, administration of general anesthesia is unavoidable. Neonatal respiratory depression with low Apgar scores, and umbilical arterial and venous pH associated with general anesthesia, is often transient. A properly administered anesthetic, whether regional or general, has no significant adverse fetal or neonatal effects.

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Section: Ketaminementioning

confidence: 99%

Effects of Obstetric Analgesics and Anesthetics on the Neonate

2003

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“…Fetal blood levels have been reported to be comparable to maternal blood levels within 2 min of maternal administration. 61 Ketamine is distributed rapidly after IV administration and plasma levels decrease rapidly thereafter. 62,63 In our recent publication, 35 we reported that the ketamine levels required to maintain anesthesia were 10 to 25 g/mL, which is 5 to 10 times higher than those observed in humans (2-3 g/mL).…”

Section: Ketamine-induced Neuronal Cell Death In the Perinatal Rhesusmentioning

confidence: 99%

Strategies and Experimental Models for Evaluating Anesthetics: Effects on the Developing Nervous System

Wang

Slikker

2008

Anesthesia &Amp; Analgesia

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Advances in pediatric and obstetric surgery have resulted in an increase in the duration and complexity of procedures requiring anesthesia. It has been reported that anesthetic drugs cause widespread and dose-dependent apoptosis in the developing rat brain. The similarity of the physiology, pharmacology, metabolism, and reproductive systems of the nonhuman primate to that of the human, especially during pregnancy, make the monkey an exceptionally good animal model for assessing potential neurotoxic effects of anesthetics. The window of vulnerability to these neuronal effects of pediatric anesthetics is restricted to the period of rapid synaptogenesis, also known as the brain growth spurt period. To minimize the risks to children resulting from the use of anesthesia, the following questions should be addressed: 1. What is the relationship between exposure and brain cell loss for drugs commonly used in the practice of pediatric anesthesia (inhaled anesthetics, midazolam, ketamine, and nitrous oxide)? 2. Are there "class effects," or does each drug need to be considered independently? 3. Are there important interactions among the drugs used as anesthetics contributing to the risk of brain cell death? 4. What is the likely period of human vulnerability? Pharmacogenomic/system biology approaches have great potential for helping to advance the understanding of brain-related biological processes, including neuronal plasticity and neurotoxicity. Because of the complexity and temporal features of how developmental neurotoxicity is manifested, pharmacogenomic/systems biology approaches may prove to be useful tools for enhancing our understanding of the biological processes induced by anesthetics. Therefore, the main purpose of this review is to describe the application of these approaches and models, as well as protection strategies, especially as regards the issue of anesthetic-induced neuronal cell death during development. Much of the discussion that follows is based on experiments conducted with ketamine. This is due in part to the use of ketamine in the early studies and the volume of preclinical experimental work performed with this drug, as well as its use in anesthetic studies in developing rodents and nonhuman primates. Although ketamine use in pediatric anesthesia is relatively limited, the findings of the studies are sufficiently strong to merit concern about the N-methyl-d-aspartate antagonist drugs as a class. Our focus on ketamine should not be construed as implying that the risk of neurodegeneration with ketamine is greater, or less, than with other anesthetics. We are simply describing the effects where we have the most preclinical data.

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“…Ketamine rapidly crosses the placenta, and the plasma concentration in mixed cord blood is similar to the maternal venous level, 1.5 to 6.5 minutes after maternal administration (Ellingson et al, 1977). Neonatal depression has been associated with the use of ketamine as an anaesthetic agent at the time of delivery (Little et al, 1972;Ellingson et al, !…”

Section: Ketaminementioning

confidence: 99%

Drug Kinetics in Childbirth

Nation¹

1980

Clinical Pharmacokinetics

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Drugs from a wide range of pharmacological classes are commonly given to women in childbirth, either for a maternal effect or a fetal/neonatal effect. A number of striking physiological and biochemical changes occur during labour and delivery that might alter drug kinetics. The rate of drug absorption from the gastrointestinal tract may be normal in labour provided that narcotic analgesics are not administered concurrently. Altered blood flow characteristics in the extremities could modify drug absorption from intramuscular injection sites. Drug distribution might be altered as a result of the presence of placental-fetal tissues, or as a consequence of changes in, for example, maternal blood volume, concentrations of proteins and other endogenous compounds, cardiac output or tissue perfusion. Although data are scanty on the status of the physiological determinants of drug clearance, that limited information available suggests that drug clearance could be altered in childbirth. The possibility of a placental and/or fetal contribution should not be overlooked when considering the clearance of drugs administered during labour and delivery. Uterine contractions, maternal posture and obstetric medication have been found to affect the extent of some of the physiological changes that occur. Consequently, drug disposition could be modified by these factors. All of the drugs given to women in childbirth are capable of crossing the placenta to some degree. This is a disadvantage in those cases where drugs are given for a maternal effect and may result in neonatal sequelae. The fetal exposure to, and neonatal burden at delivery of, drugs administered during labour and delivery may be influenced by many factors, including maternal posture, mode of drug administration, the drug administraton to delivery interval, fetal pH, and whether intravenous bolus drug administration coincides with the contraction or relaxation phase of uterine activity. Protracted elimination by the neonate may occur for those drugs acquired in utero. Realisation of this is of considerable importance in the clinical management of the newborn.

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Transplacental Passage of Ketamine after Intravenous Administration

Cited by 50 publications

References 6 publications

Effects of Obstetric Analgesics and Anesthetics on the Neonate

Effects of Obstetric Analgesics and Anesthetics on the Neonate

Strategies and Experimental Models for Evaluating Anesthetics: Effects on the Developing Nervous System

Drug Kinetics in Childbirth

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