Stephen A. Vitkun

Glutamate modulation of dopamine measured in vivo with positron emission tomography (PET) and 11C-raclopride in normal human subjects.

Subanesthetic doses of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine exacerbate psychosis in schizophrenic patients, and ketamine has significant abuse liability. These observations indicate that a secondary effect of ketamine may be to increase dopamine concentrations. The present study was undertaken using positron emission tomography (PET) and the dopamine (D2) radiotracer 11C-raclopride to determine whether ketamine would decrease D2 receptor availability, indicative of an increase in dopamine concentrations. Two scans were performed in seven male control subjects before and after administration of ketamine (0.5 mg/kg, IV infused over 20 min). Ketamine significantly increased cortisol levels and decreased dopamine receptor availability in the striatum (specific binding), but not in the cerebellum (nonspecific binding). In addition, the cerebellar binding subtracted from the striatal binding (to account for changes in nonspecific binding) was significantly decreased after ketamine administration. These results provide in vivo evidence for the ability of ketamine to increase striatal dopamine concentrations, consistent with the role of the NMDA receptor in modulating dopamine function.

Effects of Blood Flow on [11C]Raclopride Binding in the Brain: Model Simulations and Kinetic Analysis of PET Data

To assess the stability of different measures of receptor occupancy from [11C]raclopride (a D2 antagonist) studies with positron emission tomography, we analyze data from five test/retest studies in normal volunteers in terms of individual model parameters from a three-compartment model, the distribution volume (DV) and the ratio of DVs from a receptor-containing region of interest to a non-receptor-containing region. Large variations were found in the individual model parameters, limiting their usefulness as an indicator of change in receptor systems. The DV ratio showed the smallest variation. Individual differences were reflected in the greater intersubject variation in DV than intrasubject variation. The potential effects of blood flow on these measurements were addressed both experimentally and by simulation studies using three models that explicitly incorporate blood flow into a compartmental model that also includes receptor–ligand binding. None of the models showed any variation in the DV with changes in blood flow as long as flow was held constant during the simulation. Experimentally, blood flow was significantly reduced by hyperventilation in a human subject. The DV was found to be reduced relative to baseline in the hyperventilation study, but the DV ratio remained unchanged. The effect of elevated and reduced flow was also tested in two baboon experiments in which Pco2 was varied. Some variability in the DV ratio was observed but was not correlated with changes in blood flow. This raises the possibility that other factors indirectly related to changes in blood flow (or Pco2) may cause changes in DV, and these effects need to be considered when evaluating experimental results.

Acute effects of ethanol on regional brain glucose metabolism and transport.

To evaluate the effects of ethanol in the human brain, we tested six normal subjects and six alcoholics using positron emission tomography and 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) under baseline conditions and 24 hours later after ethanol administration (1 g/kg). Ethanol inhibited cortical and cerebellar glucose metabolism with relative sparing of the basal ganglia and corpus callosum. This inhibition was more pronounced in the alcoholics than in the controls. Measurement of the constants for glucose transport and utilization showed that decreased glucose metabolism was due to a reduction in glucose phosphorylation and not to a change of glucose transport into the tissue. The pattern of regional metabolic inhibition by alcohol paralleled the distribution of benzodiazepine receptors in the human brain.

Concentration and occupancy of dopamine transporters in cocaine abusers with [11C]cocaine and PET.

The concentration (Bmax) of the dopamine transporter (DAT) and the maximum and effective occupancies by cocaine doses of 0.1 mg/kg or 0.05 mg/kg were measured in the striatum of cocaine abusers (n = 12) by using [11C]cocaine as a radiotracer for the DAT and positron emission tomography (PET). Two methods based on a three‐compartment model with one binding site (the nonlinear least squares (NLSQ) and the Farde pseudoequilibrium method) were used to estimate Bmax. Effective occupancies and maximum occupancies were calculated from the distribution volume ratios (DVR) and a three‐compartment model, respectively. The NLSQ and Farde methods gave similar values of Bmax (average, 650 ± 350 pmol/ml and 776 ± 400 pmol/ml, respectively), but the individual estimates of Bmax were found to be very sensitive to small variations in other model parameters and were not correlated with the parameter Bmax/Kd (r = .07). The average maximum (and effective) occupancies were found to be 67% (50%) and 52% (39%) for the 0.1‐mg/kg and the 0.05‐mg/kg studies, respectively. The ED50 based on the effective occupancy corresponds to 0.1 mg/kg, which is significantly smaller than the ED50 of 3 mg/kg calculated from studies in which [123I]β‐CIT is displaced by cocaine. The effect on the Bmax estimate of two binding sites with different Kds is also considered by simulation.

Preoperative medical consultations: impact on perioperative management and surgical outcome

PurposeThis study was designed to assess the effect of preoperative medical consults on both perioperative management and surgical outcome.MethodsThe charts of 387 consecutive patients over the age of 50 undergoing non-cardiac, elective surgery during a six-week period were retrospectively examined. Patient factors including age, ASA status, gender, type of surgery, outcome (death, unexpected intensive care unit admission or uncomplicated discharge), presence of medical consult, and, in those cases where a medical consult was present, stated reason for the consult, the ordering physician, and recommendations of the consultant, were recorded.Results138 patients receiving medical consults (35.7%) were identified (a total of 146 consults). The most common stated purpose of the consults examined was “preoperative evaluation.” In only five consults (3.4%) did the consultant identify a new finding. Sixty-two consults (42.5%) contained no recommendations. There was no statistically significant difference in outcome between those patients who received a medical consult and those who did not.ConclusionA review of 146 medical consults suggests that the majority of such consults give little advice that truly impacts either perioperative management or outcome of surgery.RésuméObjectifÉvaluer ľeffet des consultations médicales préopératoires sur la prise en charge périopératoire et les suites opératoires.MéthodeNous avons procédé à ľexamen rétrospectif des dossiers de 387 patients consécutifs de plus de 50 ans qui, au cours de six semaines, ont été admis pour une intervention chirurgicale réglée non cardiaque. Nous avons noté ľâge, ľétat physique ASA, le type ďintervention chirurgicale, les suites (décès, admission imprévue à ľunité des soins intensifs ou absence de complications), la présence de con sultation médicale et la raison de la consultation, le médecin référant et les recommandations du consultant.RésultatsNous avons trouvé 138 patients (35,7 %) vus en consultation médicale pour un total de 146 consultations. Le motif de consultation le plus courant était «ľévaluation préopératoire». Dans cinq cas seulement (3,4 %) le consultant a découvert un nouveau problème. Soixante-deux consultations (42,5 %) ne contenaient aucune recommandation. Les suites opératoires n’étaient pas statistiquement différentes entre les patients vus ou non en consultation médicale.ConclusionUne revue de 146 consultations médicales montre que la majorité donne peu ďavis à incidence véritable sur la prise en charge périopératoire ou sur les suites postopératoires.

Use of EMLA cream in the treatment of post-herpetic neuralgia

EMLA cream is an acronym for eutectic mixture of local anesthetics. It contains lidocaine and prilocaine creams. A eutectic preparation, applied topically, penetrates into the dermis after an application period of 1 to 2 hours. This case report describes the successful treatment with EMLA cream of post-herpetic neuralgia, which was resistant to other modes of therapy, and briefly discusses the pharmacology of EMLA cream.

Arterial oxygen desaturation in adult dental patients receiving conscious sedation

Forty-six adults undergoing dental procedures were monitored with a pulse oximeter for hypoxemia. Thirty-six patients received various amounts and combinations of central nervous system depressant drugs (barbiturates, sedatives, and narcotics) in addition to local anesthetics to produce a state of conscious sedation. Twenty-eight patients in the latter group received supplemental oxygen. Ten subjects served as a control group and received only local anesthesia without supplemental oxygen. Continuous monitoring by pulse oximetry revealed 151 episodes of mild, 132 of moderate, and 33 of severe arterial oxygen desaturation, although clinical signs of hypoxemia were absent. Patients with a body mass index greater than 30 or those with a smoking history greater than 30 pack-years were particularly prone to arterial oxygen desaturation.

Bronchodilating effects of the anesthetic ketamine in an in vitro guinea pig preparation

Ketamine, a dissociative anesthetic, is capable of reducing airway resistance and has proved useful in anesthetizing surgical patients with acute or chronic bronchospasm. To determine if ketamine alters smooth muscle tone, the relative responses of large and small airways of the same animal were studied by comparing the pharmacologic reactivity of tracheal smooth muscle strips with that of a specially prepared perfused bronchial tree. Trachealis and bronchial smooth muscle were found to react to methacholine and histamine in a concentration-dependent manner and have similar sensitivities. Ketamine, by itself, in the concentration range 10−8–10−3 M did not alter resting tone as compared to epinephrine, which reduced baseline tone. In tissues precontracted with histamine or methacholine at ED50 doses, ketamine inhibited smooth muscle contraction. In a second series of experiments, the dose-dependent contraction of smooth muscle to histamine and methacholine was reevaluated in the presence of ketamine. Both tissue sensitivity and maximum contractile response to these agonists were reduced by ketamine at 10−4 M. These data indicate that ketamine alters the in vitro response of guinea pig airways to agonists associated with the asthmatic state. Although ketamine does not reduce airway tone in nonstimulated tissues, its effects on agonist-induced contraction of airway tissues in vitro are consistent with clinical observations that ketamine relieves bronchospasm.

Application of the Grieshaber® air system to maintain endotracheal tube cuff pressure

The Grieshaber Air System was designed to maintain intraocular pressure during ophthalmologic surgery. It also has been used to maintain pressure in leaking endotracheal tube cuffs. It is a very useful device, especially if the intubation is difficult or the patients position precludes replacement of the endotracheal tube. Two patients are presented in whom the system was used to maintain endotracheal tube cuff pressure.

Anesthetic management of a patient with neuroleptic malignant syndrome

Neuroleptic malignant syndrome is an uncommon, idiosyncratic, and sometimes life-threatening disorder associated with the use of neuroleptic drugs. The pathogenesis of neuroleptic malignant syndrome is uncertain, but it may be similar to that of malignant hyperthermia (MH). Some of the symptoms of neuroleptic malignant syndrome are similar to those of MH. We anesthetized a 17-year-old man with this syndrome multiple times for electroconvulsive therapy (ECT) using a variety of anesthetic techniques. In this patient, dantrolene pretreatment and the use of nondepolarizing muscle relaxants did not relieve symptoms of the syndrome, including fever and creatine phosphokinase (CPK) increases.