The new oral anticoagulants are approved for a variety of clinical syndromes, including the prevention of stroke in atrial fibrillation, acute coronary syndromes, treatment of venous thromboembolism (VTE), and prevention of venous thrombosis after total joint surgery or hip fracture. Published guidelines have differing recommendations on the safe interval between discontinuation of the anticoagulant and performance of neuraxial procedures and between the interventional procedure and redosing of the drug. While two to three half-life intervals might be acceptable in patients who are at high risk for VTE or stroke, an interval of four to six half-lives between discontinuation of the drug and neuraxial injections is probably safer in most patients at low risk of thrombosis. In those with renal disease, the interval should be based on creatinine clearance. After a neuraxial procedure or removal of an epidural catheter, anticoagulants can be resumed within 24-48 h in most patients, but they can be taken sooner in patients who are at higher risk for VTE or stroke, that is, 24 h minus the time to peak effect of the drug. The new antiplatelet drugs prasugrel and ticagrelor should be stopped 7 or 5 days, respectively, before a neuraxial injection and can be restarted 24 h later. In selected situations, laboratory monitoring of the anticoagulant effect is appropriate, and reversal agents are suggested when there is a need to rapidly restore haemostatic function.

A thermally generated aerosol (TGA) system can effect reliable delivery of excipient-free drug to alveoli, resulting in rapid systemic drug absorption. We developed a pharmacokinetic model of prochlorperazine, administered by inhalation and as a rapid intravenous infusion, and we determined absolute TGA bioavailability in eight healthy volunteers in this institutional review board-approved, two-period crossover study. After the drug was administered as either a 5-s intravenous infusion or a TGA single-breath inhalation, blood was collected at various times for up to 24 h. Plasma prochlorperazine concentrations were measured using liquid chromatography-tandem mass spectrometry. Inhalation and rapid intravenous administration produced similar plasma prochlorperazine concentration profiles. Intravenous and inhalation pharmacokinetics were well characterized by a simultaneous two-compartment model with multiple absorption delays. Prochlorperazine pharmacokinetic parameters were similar to those reported for single intravenous doses. The geometric mean bioavailability after TGA delivery was 1.10. The administration of prochlorperazine by inhalation resulted in pharmacokinetics similar to that seen after intravenous administration, in terms of speed, extent, and consistency of absorption.

There is considerable variability in response to intravenously administered anesthetic drugs (e.g., hypnotics, benzodiazepines, and narcotics) that have a rapid onset of effect (such as hypnosis, anxiolysis, and analgesia) and a low margin of safety (because of cardiovascular or respiratory depression, etc.). Although the onset of effect for these drugs occurs seconds to minutes after injection, traditional pharmacokinetic models are based on blood samples that are first obtained after drug effects have peaked. As a result, many studies have failed to provide a pharmacokinetic rationale for dosage adjustments of these drugs.

Opioids are the mainstay of treatment for moderate to severe pain. However, opioid therapy in the elderly is often associated with significant morbidity because of excessive ventilatory depression. The large amount of interindividual variability in opioid dose-response relationships makes it difficult to individualize the dose and dosing interval to provide safe and effective analgesia. By examining how aging affects the pharmacokinetics (PK) and pharmacodynamics (PD) of opioids, it is possible to provide a rational basis for age adjustment in opioid dosing.

hemorrhage. This randomized, controlled trial compared the effectiveness, safety, and adverse effects of terbutaline and nifedipine in prolonging pregnancy beyond 48 hours.Patients who were enrolled in the trial had 1 to 3 uterine contractions per 10 minutes interval for at least 60 minutes, cervical dilation of 0 to 3 cm for primigravidas, and 1 to 3 cm for multigravidas, with effacement <50%. One group of patients received a 0.25 mg loading dose of terbutaline subcutaneously and the same dose was repeated every 45 minutes if contractions continued if the patients' pulse did not exceed 120 bpm. The other women were given an oral 30 mg loading dose of nifedipine followed by 20 mg orally 90 minutes later. If contractions did not stop, 20 mg oral nifedipine was given every 8 hours for 48 hours. All patients had blood pressure and serum chemistries monitored; the primary outcome was pregnancy prolongation for 48 hours.A total of 174 women were randomized to the treatment arms, 95 in the terbutaline group and 79 in the nifedipine group. The groups were similar in mean age, parity, gestational age confirmed by date and by ultrasound, and presence of multiple gestations. Treatment had success rates of 87.4% and 89.9%, in the terbutaline and nifedipine groups respectively for suppressing PTL for 48 hours or greater. Five women in the terbutaline group and 3 in the nifedipine group delivered within 48 hours. Length of hospital stay and time to delivery were similar for the 2 groups. Maternal palpitations and vomiting and fetal tachycardia occurred more frequently in the terbutaline group (P<0.001; P = 0.04; P = 0.002, respectively); nifedipine was associated with a greater incidence of maternal hypotension (P = 0.002). Nifedipine was associated with lower systolic and diastolic blood pressures at 3 hours but the two groups did not differ at 24 and 48 hours. The drugs did not differ with regard to their effects on uterine contraction and cervical dilation.Terbutaline and nifedipine seem to be equally effective in suppressing uterine contraction during PTL. Nifedipine is easier to administer, creates significantly less maternal and fetal tachycardia, and costs less than terbutaline. These findings suggest that it has significant advantages over terbutaline when used to suppress uterine contractility for 48 hours during PTL.A lthough a preoperative fast traditionally has been recommended to reduce the risk of aspiration in surgical patients, the reduction in risk for pregnant patients remains unclear. Recent studies indicate gastric emptying in term nonlaboring patients is similar to that of patients who are not pregnant. The 2006 American Society of Anesthesiologists Practice Guidelines for Obstetric Anesthesia reflect this and suggest pregnant women with no complications undergoing elective cesarean delivery may adhere to the same presurgical fasting guidelines as nonpregnant women. The safety of this practice in obese pregnant women has not been studied. This crossover study compared gastric emptying in obese, term, and ...