Evaluation of Waste Anesthetic Gas in the Postanesthesia Care Unit within the Patient Breathing Zone.

Potential health hazards from waste anesthetic gases (WAGs) have been a concern since the introduction of inhalational anesthetics into clinical practice. The potential to exceed recommended exposure levels (RELs) in the postanesthesia care unit (PACU) exists. The aim of this pilot study was to assess sevoflurane WAG levels while accounting for factors that affect inhalational anesthetic elimination. In this pilot study, 20 adult day surgery patients were enrolled with anesthesia maintained with sevoflurane. Following extubation, exhaled WAG from the patient breathing zone was measured 8 inches from the patient's mouth in the PACU. Maximum sevoflurane WAG levels in the patient breathing zone exceeded National Institute for Occupational Safety and Health (NIOSH) RELs for every 5-minute time interval measured during PACU Phase I. Observed WAGs in our study were explained by inhalational anesthetic pharmacokinetics. Further analysis suggests that the rate of washout of sevoflurane was dependent on the duration of anesthetic exposure. This study demonstrated that clinically relevant inhalational anesthetic concentrations result in sevoflurane WAG levels that exceed current RELs. Evaluating peak and cumulative sevoflurane WAG levels in the breathing zone of PACU Phase I and Phase II providers is warranted to quantify the extent and duration of exposure.

Perioperative assessment of platelet function by Thromboelastograph Platelet Mapping in cardiovascular patients undergoing non-cardiac surgery.

UNLABELLED: Five percent of patients on dual antiplatelet therapy after coronary artery stent implantation will need non-cardiac surgery within the first year of therapy, and many more will need surgery later on. A function assay that evaluates platelet reactivity and inhibition by drug therapy is beneficial for such patients. Platelet Mapping assay (PM) using the TEG analyzer was tested in surgical patients. After IRB approval, 60 patients on combined aspirin and clopidogrel therapy were consented and enrolled. The TEG maximal amplitude (MA) and the percentage (%) platelet inhibition were recorded and analyzed. Fifty-seven patients (mean age 65.7 ± 10.9 years) had preoperative data only. Distribution of preoperative ADP (43.6 ± 24.4%) and AA inhibition (52.8 ± 30.2%) was determined, as well as for the preoperative MA ADP (43.1 ± 15.9 mm) and MA AA (37.2 ± 19.6 mm), showing an offset of the effect of both medications starting from day 3. Patients with complete pre- and postoperative data were stratified depending on duration off antiplatelet therapy (≤3 days, 3-7 days and >7 days): n = 27, ADP % preop inhibition (43.2 ± 21.6%), ADP % postop inhibition (32.3 ± 18.3%), p = 0.048. Distribution of immediate pre- and post- ADP and AA % inhibitions, showing a possible reduction in Δ of inhibition for clopidogrel at 3 days, were also assessed. CONCLUSION: According to the findings, the TEG PM assay might be a feasible approach to objectively evaluate the effects of aspirin and clopidogrel during the perioperative period and potentially guide drug management.

Impact of ovarian hormones on the modulation of the serotonin transporter by fluvoxamine.

Most preclinical studies examining the mechanism(s) of action of antidepressants are carried out using male animals. Blockade of serotonin transporter (SERT) function by selective serotonin reuptake inhibitors (SSRIs) is the initial event that triggers a not completely understood process that results in clinical improvement in depression. To investigate whether there are differences in the ability of SSRIs to inhibit the SERT between male and female rats at different phases of the estrous cycle, clearance of locally applied serotonin (5-HT) was measured by in vivo chronoamperometry. Local application of the SSRI, fluvoxamine, directly into the CA3 area of hippocampus increased significantly 5-HT clearance time parameters in male rats and female rats in estrus or diestrus, but not in proestrus. The contribution of ovarian steroids to this result was investigated in ovariectomized (OVX) rats treated with estradiol benzoate (EB) and/or progesterone (P). In OVX-control rats, fluvoxamine increased clearance time parameters, whereas EB and/or P treatment blocked this effect, consistent with what was seen in female rats in proestrus. This effect was gender-specific, since treatment of castrated rats with EB/P had no effect on the ability of fluvoxamine to slow 5-HT clearance. The time course of hormonal effects showed that 1-60 min after local application of 17-beta-estradiol (E(2)) into the CA3 region of OVX rats, fluvoxamine had no effect on clearance time of 5-HT. E(2)-BSA mimicked E(2)'s effects at 10 min but not at 60 min. Pretreatment with estrogen receptor antagonists blocked the effects of E(2). The finding that acutely both estradiol and progesterone can inhibit the ability of an SSRI to slow the clearance of 5-HT, may have important implications for the use of SSRIs in women.

A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters.

BACKGROUND: Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT. Serotonergic effects occur with lower doses, whereas both serotonergic and noradrenergic effects occur with higher doses of venlafaxine. Chronic treatment of rats with selective serotonin reuptake inhibitors decreases SERT binding sites, whereas similar treatment with selective norepinephrine reuptake inhibitors decreases NET binding sites. We hypothesized that venlafaxine would affect monoamine transporters dose-dependently, with low doses causing selective reduction of SERT binding sites and higher doses reducing both SERT and NET binding sites. METHODS: Rats were treated for 21 days with a low (15 mg/kg/day) or high (70 mg/kg/day) dose of venlafaxine, vehicle, or other antidepressants. The SERT and NET density was determined by quantitative autoradiography. RESULTS: Neither dose of venlafaxine nor amitriptyline reduced binding to either the SERT or NET. In rats with noradrenergic terminals destroyed by 6-hydroxydopamine, venlafaxine still failed to reduce SERT binding. Also, rats treated simultaneously with sertraline plus desipramine exhibited reductions in both SERT and NET binding. CONCLUSIONS: Chronic venlafaxine treatment affected SERT and NET binding differently from paroxetine or desipramine. The inability of venlafaxine to reduce SERT or NET binding sites is not due to its dual uptake inhibiting properties.

Regulation of the norepinephrine transporter by chronic administration of antidepressants.

BACKGROUND: Downregulation of serotonin transporter was observed previously after chronic treatment with selective serotonin reuptake inhibitors (SSRIs) but not selective norepinephrine reuptake inhibitors (NRIs). This study investigated if chronic treatment of rats with selective NRIs or SSRIs also affected the norepinephrine transporter (NET). METHODS: Rats were treated for 3 to 6 weeks by osmotic minipumps with either the selective NRIs, desipramine, or the SSRI paroxetine. RESULTS: [(3)H]nisoxetine binding sites as well as [(3)H]norepinephrine uptake were decreased in hippocampus and cortex after treatment with desipramine. By contrast, paroxetine-treated rats showed no alteration in either [(3)H]nisoxetine binding or [(3)H]norepinephrine uptake. NET messenger RNA levels in the locus coeruleus were unchanged by desipramine treatment. CONCLUSIONS: These results demonstrate that the marked decrease in NET density 1) is not a consequence of a decrease in gene expression; 2) was caused only by a selective NRI; and 3) was associated with a parallel decrease in norepinephrine uptake.