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Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third-trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (approximately 100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide evidence that cocaine use by a pregnant mother will also affect the function of the fetal brain. We are also unique in showing that cocaine's effects in brain glucose metabolism differed in pregnant (increased) and nonpregnant (decreased) animals, which suggests that the psychoactive effects of cocaine are influenced by the state of pregnancy. Our findings have clinical implications because they imply that the adverse effects of prenatal cocaine exposure to the newborn child include not only cocaine's deleterious effects to the placental circulation, but also cocaine's direct pharmacological effect to the developing fetal brain.

Unlabelled: An understanding of how drugs are transferred between mother and fetus during the gestational period is an important medical issue of relevance to both therapeutic drugs and drugs of abuse. Though there are several in vitro and in vivo methods to examine this issue, all have limitations. Furthermore, ethical and safety considerations generally preclude such studies in pregnant humans. PET and appropriately labeled compounds have the ability to provide information on both maternal-fetal drug pharmacokinetics and pharmacodynamics. We present here a nonhuman primate animal model and the methodology for combining PET and MRI to identify fetal organs and to measure maternal and fetal isotope distribution using (18)F-FDG and a whole-body imaging protocol to demonstrate proof-of-principle., Methods: One nonpregnant nonhuman primate was used for determination of the anesthesia protocol and MRI methods and 3 pregnant nonhuman primates (Macaques radiata) weighing 4.5-7 kg were used for the imaging study and anesthetized with propofol (160-300 micro g/kg/min). Anatomic T2-weighted MR images were acquired on a 4-T MR instrument. Subsequently, whole-body PET images were acquired 35 min after injection of (18)F-FDG, and standardized uptake values (SUVs) were calculated. Image processing and coregistration were performed using commercial software., Results: All animals underwent uneventful general anesthesia for a period of up to 7 h. Coregistration of PET and MR images allowed identification of fetal organs and demonstrated that (18)F-FDG readily crosses the placenta and that (18)F accumulates in both maternal and fetal brain, heart, and bladder. Brain SUVs averaged 1.95 +/- 0.08 (mean +/- SD) and 1.58 +/- 0.11 for mothers and fetuses, respectively. Monkeys delivered healthy babies after a normal gestational term of 170 d following the PET/MRI study., Conclusion: The pregnant macaque in combination with PET and MRI technology allows the measurement of radioisotope distribution in maternal and fetal organs. This demonstrates the potential for noninvasively measuring the transfer of drugs across the placenta and for measuring the fetal drug distribution. It also opens up the possibility for studying binding and elimination as well as the effects of a drug on specific cellular elements and physiologic processes during the gestational period in a primate model.

Induction, emergence and recovery characteristics were compared during sevoflurane or halothane anaesthetic in a large (428) multicentre, international study of children undergoing elective inpatient surgical procedures. Two hundred and fourteen children in each group underwent inhalation induction with nitrous oxide/oxygen and sevoflurane or halothane. Incremental doses of either study drug were added until loss of eyelash reflex was achieved. Steady state concentrations of anaesthesia were maintained until the end of surgery when anaesthetic agents were terminated simultaneously. Time variables were recorded for induction, emergence and the first need for analgesia in the recovery room. In addition, in 86 of the children in both groups, venous blood samples were drawn for plasma fluoride levels during and after surgery. There was a trend toward smoother induction (induction of anaesthesia without coughing, breath holding, excitement laryngospasm, bronchospasm, increased secretion, and vomiting) in the sevoflurane group with faster induction (2.1 min vs 2.9 min, P = 0.037) and rapid emergence times (10.3 min vs 13.9 min, P = 0.003). Among the children given sevoflurane, 2% developed bradycardia compared with 11% in the halothane group. Postoperatively, 46% of the children in the halothane group developed nausea and or vomiting versus 31% in the sevoflurane group (P = 0.002). Two children in the halothane group developed cardiac dysrhythmia and were dropped from the study. In addition, a child in the halothane group developed malignant hyperthermia, received dantrolene, and had an uneventful recovery. Mean maximum inorganic fluoride concentration was 18.3 microM.l-1. The fluoride concentrations peaked within one h of termination of sevoflurane anaesthetic and returned rapidly to baseline within 48 h. This study suggests that sevoflurane may be the drug of choice for the anaesthetic management of children.

We present a patient with Parkinson's disease who experienced laryngeal spasm after tracheal extubation without having been anesthetized. This patient's trachea was intubated because of respiratory arrest. We postulate that her postextubation laryngospasm was related to Parkinson's disease.

Nimodipine is a calcium antagonist that binds with high affinity to neuronal membranes. It is a potent cerebrovasodilator and has been demonstrated also to affect neurotransmitter synthesis and release. Because patients undergoing surgery for intracranial aneurysms are frequently receiving nimodipine, the authors determined the MAC of isoflurane in six dogs before and during three infusion doses of nimodipine (0.5, 1.0 and 2.0 micrograms.kg-1.min-1). MAC was also determined in five dogs before and during infusion of the drug vehicle (10 microliters.kg-1.min-1). Nimodipine produced a reduction in MAC from 1.47 +/- 0.33% to 1.19 +/- 0.18, 1.15 +/- 0.18 and 1.15 +/- 0.09% during infusions of nimodipine 0.5, 1.0 and 2.0 micrograms.kg-1.min-1, respectively (P less than 0.05). Infusion of drug vehicle alone produced no change in MAC (1.39 +/- 0.15%). This reduction in anaesthetic requirement by nimodipine may be due to its effect on neurotransmission. Adjustments in anaesthetic dosage may be necessary in patients receiving nimodipine.

Brachial plexus blockade is a commonly used technique for providing surgical anesthesia for the upper extremity. Although various approaches have been described, the axillary approach is the safest and most frequently used. Most complications associated with axillary nerve block are related to local or systemic anesthetic toxicity, bleeding, infection, and nerve damage. A case of false aneurysm of the axillary artery following axillary nerve block is reported. The possible occurrence of this complication should be kept in mind to avoid permanent neurologic sequelae.

The effects of age (older than 70 yr) on the pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) and metocurine (MTc) were evaluated in studies of 21 patients aged 70-87 and 21 patients aged 29-59. There was a significant difference in the pharmacokinetic parameters of all elderly patients compared with younger controls. With both dTc and MTc, the elderly exhibited a decreased plasma clearance, decreased initial volume of distribution, decreased volume of distribution, and a prolonged elimination half-life. After 0.3 mg/kg of dTc, the times for 50% return of twitch and recovery index (25-75% return of twitch response) in the elderly were significantly longer than in the young (P less than 0.02). A similar observation was made for the elderly patients receiving 0.15 mg/kg of MTc. No significant difference was seen in the log plasma concentration-twitch response relationship between 20-80% paralysis in young and in elderly patients receiving dTc. There was a similar lack of significant difference between the log plasma concentration-twitch response lines for elderly and young patients receiving MTc. Because there was no difference between the plasma concentration-response relationships in the elderly and young, altered sensitivity to dTc or MTc cannot explain the longer duration of action seen in the elderly. The most likely explanation for this difference is the altered pharmacokinetics of these two drugs in the elderly.

Vascular patency after reimplantation has been evaluated by numerous methods. A patient is described in whom pulse oximetry was used for this purpose. Other techniques of evaluating vascular patency are mentioned, and the physics of pulse oximetry are briefly discussed.