Desflurane Allows for a Faster Emergence When Compared to Sevoflurane without Affecting the Baseline Cognitive Recovery Time.

AIMS: We compared the effect of desflurane and sevoflurane on anesthesia recovery time in patients undergoing urological cystoscopic surgery. The Short Orientation-Memory-Concentration Test (SOMCT) measured and compared cognitive impairment between groups and coughing was assessed throughout the anesthetic. METHODS AND MATERIALS: This investigation included 75 ambulatory patients. Patients were randomized to receive either desflurane or sevoflurane. Inhalational anesthetics were discontinued after removal of the cystoscope and once repositioning of the patient was final. Coughing assessment and awakening time from anesthesia were assessed by a blinded observer. STATISTICAL ANALYSIS USED: Statistical analysis was performed by using t-test for parametric variables and Mann-Whitney U test for non-parametric variables. RESULTS: The primary endpoint, mean time to eye-opening, was 5.0 ± 2.5 min for desflurane and 7.9 ± 4.1 min for sevoflurane (p < 0.001). There were no significant differences in time to SOMCT recovery (p = 0.109), overall time spent in the post-anesthesia care unit (PACU) (p = 0.924) or time to discharge (p = 0.363). Median time until readiness for discharge was 9 min in the desflurane group, while the sevoflurane group had a median time of 20 min (p = 0.020). The overall incidence of coughing during the perioperative period was significantly higher in the desflurane (p = 0.030). CONCLUSION: We re-confirmed that patients receiving desflurane had a faster emergence and met the criteria to be discharged from the PACU earlier. No difference was found in time to return to baseline cognition between desflurane and sevoflurane.

Triple Therapy with Scopolamine, Ondansetron, and Dexamethasone for Prevention of Postoperative Nausea and Vomiting in Moderate to High-Risk Patients Undergoing Craniotomy Under General Anesthesia: A Pilot Study.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is one of the most common complaints from patients and clinicians after a surgical procedure. According to the current Society of Ambulatory Anesthesia Consensus Guidelines, the general incidence of vomiting and nausea is around 30 and 50%, respectively; and up to 80% in high-risk patients. In previous studies, the reported incidence of PONV at 24 h after craniotomy was 43-70%. The transdermal scopolamine (TDS) delivery system contains a 1.5-mg drug reservoir, which is designed to deliver a continuous slow release of scopolamine through intact skin during the first 72 h of patch application. Therefore, we designed this single arm, non-randomized, pilot study to assess the efficacy and safety of triple therapy with scopolamine, ondansetron, and dexamethasone to prevent PONV. MATERIALS AND METHODS: In the preoperative area, subjects received an active TDS 1.5 mg that was applied to a hairless patch of skin in the mastoid area approximately 2 h prior to the operation. Immediately after anesthesia induction, all patients received a single 4 mg dose of ondansetron IV and a single 10 mg dose of dexamethasone IV. Patients who experienced nausea and/or vomiting received ondansetron 4 mg IV as the initial rescue medication. Postoperative nausea and vomiting assessments were performed for up to 120 h after surgery. RESULTS: A total of 36 subjects were analyzed. The overall incidence of PONV during the first 24 h after neurological surgery was 33% (n = 12). The incidence of nausea and emesis during the first 24 h after surgery was recorded as 33% (n = 12) and 16% (n = 6), respectively. CONCLUSION: Our data showed that this triple therapy regimen may be an efficient alternative regimen for PONV prophylaxis in patients undergoing neurological surgery with general anesthesia. Further studies using regimens affecting different receptor pathways should be performed to better prove the efficacy and safety in the prevention or delay of PONV.

The effect of transdermal scopolamine for the prevention of postoperative nausea and vomiting.

Postoperative nausea and vomiting (PONV) is one of the most common and undesirable complaints recorded in as many as 70-80% of high-risk surgical patients. The current prophylactic therapy recommendations for PONV management stated in the Society of Ambulatory Anesthesia (SAMBA) guidelines should start with monotherapy and patients at moderate to high risk, a combination of antiemetic medication should be considered. Consequently, if rescue medication is required, the antiemetic drug chosen should be from a different therapeutic class and administration mode than the drug used for prophylaxis. The guidelines restrict the use of dexamethasone, transdermal scopolamine, aprepitant, and palonosetron as rescue medication 6 h after surgery. In an effort to find a safer and reliable therapy for PONV, new drugs with antiemetic properties and minimal side effects are needed, and scopolamine may be considered an effective alternative. Scopolamine is a belladonna alkaloid, α-(hydroxymethyl) benzene acetic acid 9-methyl-3-oxa-9-azatricyclo non-7-yl ester, acting as a non-selective muscarinic antagonist and producing both peripheral antimuscarinic and central sedative, antiemetic, and amnestic effects. The empirical formula is C17H21NO4 and its structural formula is a tertiary amine L-(2)-scopolamine (tropic acid ester with scopine; MW = 303.4). Scopolamine became the first drug commercially available as a transdermal therapeutic system used for extended continuous drug delivery during 72 h. Clinical trials with transdermal scopolamine have consistently demonstrated its safety and efficacy in PONV. Thus, scopolamine is a promising candidate for the management of PONV in adults as a first line monotherapy or in combination with other drugs. In addition, transdermal scopolamine might be helpful in preventing postoperative discharge nausea and vomiting owing to its long-lasting clinical effects.

Hypersensitivity reactions to quinolones.

Quinolones are one of the most important classes of antimicrobial agents discovered in the recent years and one of the most widely used classes of antibiotics in clinical medicine. Their broad spectrum of activity and pharmacokinetic properties make them ideal agents for treating a variety of infections. Their clinical importance is further demonstrated by their activity against a wide range of diseases of public health importance such as anthrax, tuberculosis, bacterial pneumonia, and sexually transmitted diseases. Like other antibiotics, quinolones can cause various, sometimes dangerous hypersensitivity reactions. The underlying pathomechanisms are only poorly understood. Some are thought to be partly non-immune mediated reactions, others are considered to be IgE- or T cell-mediated reactions. This review gives an insight into the different immunological mechanisms leading to the diverse symptoms of quinolone-induced hypersensitivity reactions, with special emphasis on the role of T cells in such reactions.

Transfection of drug-specific T-cell receptors into hybridoma cells: tools to monitor drug interaction with T-cell receptors and evaluate cross-reactivity to related compounds.

In the context of drug hypersensitivity, our group has recently proposed a new model based on the structural features of drugs (pharmacological interaction with immune receptors; p-i concept) to explain their recognition by T cells. According to this concept, even chemically inert drugs can stimulate T cells because certain drugs interact in a direct way with T-cell receptors (TCR) and possibly major histocompatibility complex molecules without the need for metabolism and covalent binding to a carrier. In this study, we investigated whether mouse T-cell hybridomas transfected with drug-specific human TCR can be used as an alternative to drug-specific T-cell clones (TCC). Indeed, they behaved like TCC and, in accordance with the p-i concept, the TCR recognize their specific drugs in a direct, processing-independent, and dose-dependent way. The presence of antigen-presenting cells was a prerequisite for interleukin-2 production by the TCR-transfected cells. The analysis of cross-reactivity confirmed the fine specificity of the TCR and also showed that TCR transfectants might provide a tool to evaluate the potential of new drugs to cause hypersensitivity due to cross-reactivity. Recombining the alpha- and beta-chains of sulfanilamide- and quinolone-specific TCR abrogated drug reactivity, suggesting that both original alpha- and beta-chains were involved in drug binding. The TCR-transfected hybridoma system showed that the recognition of two important classes of drugs (sulfanilamides and quinolones) by TCR occurred according to the p-i concept and provides an interesting tool to study drug-TCR interactions and their biological consequences and to evaluate the cross-reactivity potential of new drugs of the same class.

Successful outcome of progressive multifocal leukoencephalopathy in a renal transplant patient.

We report the case of a 47-year-old man who developed progressive multifocal leukoencephalopathy (PML) after receiving immuno-suppressive therapy for renal transplantation. The patient presented with a focal seizure and cognitive changes 5 months post-transplantation. He was found to have enhancing lesions in the parietal lobe and typical findings of PML in a brain biopsy. Immunosuppression was discontinued and the neurological symptoms gradually resolved over a period of 4 weeks. The patient is free of any neurological symptoms 36 months after the diagnosis of PML and imaging studies demonstrate resolution of the PML lesions. The patient returned to hemodialysis 3 months after immunosuppression was discontinued. We also present a review of the literature on PML in renal transplant recipients.

Drug interaction with T-cell receptors: T-cell receptor density determines degree of cross-reactivity.

BACKGROUND: Immune-mediated adverse reactions to drugs are often due to T-cell reactivity, and cross-reactivity is an important problem in pharmacotherapy. OBJECTIVE: We investigated whether chemical inert drugs can stimulate T cells through their T-cell receptor (TCR) and analyzed the cross-reactivities to related compounds. METHODS: We transfected human TCRs isolated from two drug-reactive T-cell clones (TCCs) by PCR into a TCR-negative mouse T-cell hybridoma. The TCCs were isolated from a patient with drug hypersensitivity to the antibacterial sulfonamide sulfamethoxazole (SMX). RESULTS: The transfectants reacted to SMX only in the presence of antigen-presenting cells (APCs). Glutaraldehyde-fixed APCs, however, were sufficient to elicit T-cell stimulation, indicating a processing-independent direct interaction of the drug with the TCR and MHC molecule. The transfected hybridomas secreted IL-2 in a drug dose-dependent manner, whereas the degree of reactivity was dependent on the level of TCR expression. One transfectant reacted not only to SMX but also to related sulfonamide compounds. Interestingly, high TCR expression increased cross-reactivity to other structurally related compounds. In addition, SMX-specific TCR cross-reacted only with sulfonamides bearing a sulfanilamide core structure but not with sulfonamides such as celecoxib, furosemide, or glibenclamide. CONCLUSIONS: These results demonstrate that the T-cell reactivity to drugs is solely determined by the TCR. Moreover, these results show that cross-reactivity of structurally similar compounds correlates with the density of the TCR. Stably transfected T-cell hybridomas may represent a powerful screening tool for cross-reactivity of newly generated sulfonamide-containing compounds such as celecoxib.