Anesthesia and analgesia
-
Anesthesia and analgesia · Aug 2012
Comparative StudyIn vivo and in vitro pharmacological studies of methoxycarbonyl-carboetomidate.
We previously developed 2 etomidate analogs that retain etomidate's favorable hemodynamic properties but whose adrenocortical effects are reduced in duration or magnitude. Methoxycarbonyl (MOC)-etomidate is rapidly metabolized and ultrashort acting whereas (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) does not potently inhibit 11β-hydroxylase. We hypothesized that MOC-etomidate's labile ester could be incorporated into carboetomidate to produce a new agent that possesses favorable properties individually found in each agent. We describe the synthesis and pharmacology of MOC-(R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (MOC-carboetomidate), a "soft" analog of carboetomidate. ⋯ MOC-carboetomidate is a GABA(A) receptor modulator with potent hypnotic activity that is more rapidly metabolized and cleared from the brain than carboetomidate, maintains hemodynamic stability similar to carboetomidate, and does not suppress adrenocortical function.
-
Anesthesia and analgesia · Aug 2012
The frequency and magnitude of cerebrospinal fluid pulsations influence intrathecal drug distribution: key factors for interpatient variability.
Intrathecal drug delivery is an efficient method to administer therapeutic molecules to the central nervous system. However, even with identical drug dosage and administration mode, the extent of drug distribution in vivo is highly variable and difficult to control. Different cerebrospinal fluid (CSF) pulsatility from patient to patient may lead to different drug distribution. Medical image-based computational fluid dynamics (miCFD) is used to construct a patient-specific model to quantify drug transport as a function of a spectrum of physiological CSF pulsations. ⋯ Our computations identify key variables for patient to patient variability in drug distribution in the spine observed clinically. The speed of drug transport is strongly affected by the frequency and magnitude of CSF pulsations. Toxicity risks associated with an injection can be reduced for a particular patient by adjusting the infusion variables with our rigorous miCFD model.
-
Anesthesia and analgesia · Aug 2012
Time delay of monitors of the hypnotic component of anesthesia: analysis of state entropy and index of consciousness.
Monitors evaluating the hypnotic component of anesthesia by analyzing the electroencephalogram (EEG) may help to decrease the incidence of intraoperative awareness with recall. To calculate an index representing the anesthetic level, these monitors have different time delays until the correct index is displayed. In previous studies, intraoperatively recorded real and simulated EEG signals were used to determine time delays of cerebral state and Narcotrend and Bispectral indices. ⋯ Time delays were dependent on starting and target index values. Time delays of index calculation may limit the investigated monitor's ability to prevent interoperative awareness with recall. Different time delays for increasing and decreasing transitions could be a problem if the monitors are used for pharmacodynamic studies.
-
Anesthesia and analgesia · Aug 2012
Antihyperalgesic effects of myrsinoic acid B in pain-like behavior induced by inflammatory and neuropathic pain models in mice.
Myrsinoic acid B (MAB) is a diprenylated benzoic acid widely found in the vegetal kingdom. Recent studies demonstrate that MAB has important antinociceptive effects in models of chemically or thermally induced nociception in mice. ⋯ MAB reduced mechanical and thermal hypersensitivity in mice submitted to models of inflammatory and neuropathic pain, showing excellent potential for treating persistent pain in humans.
-
Anesthesia and analgesia · Aug 2012
Randomized Controlled Trial Multicenter StudyThere is no association between the circadian clock gene HPER3 and cognitive dysfunction after noncardiac surgery.
The specific clock-gene PERIOD3 is important with regard to circadian rhythmicity, sleep homeostasis, and cognitive function. The allele PER3(5/5) has been associated with worse cognitive performance in response to sleep deprivation. We hypothesized that patients with the PER3(5/5) genotype would have an increased risk of postoperative cognitive dysfunction (POCD) 1 week after noncardiac surgery. ⋯ No significant association was found between the clock-gene PER3(5/5) genotype and POCD at 1 week after noncardiac surgery. If PER3(5/5) does worsen cognitive performance, the incidence is <10% of patients.