PIP2 in pancreatic ß-cells regulates voltage-gated calcium channels by a voltage-independent pathway.

Phosphatidylinositol-4,5-bisphosphate (PIP2) is a membrane phosphoinositide that regulates the activity of many ion channels. Influx of calcium primarily through voltage-gated calcium (CaV) channels promotes insulin secretion in pancreatic ß-cells. However, whether CaV channels are regulated by PIP2, as is the case for some non-insulin-secreting cells, is unknown. The purpose of this study was to investigate whether CaV channels are regulated by PIP2 depletion in pancreatic ß-cells through activation of a muscarinic pathway induced by oxotremorine methiodide (Oxo-M). CaV channel currents were recorded by the patch-clamp technique. The CaV current amplitude was reduced by activation of the muscarinic receptor 1 (M1R) in the absence of kinetic changes. The Oxo-M-induced inhibition exhibited the hallmarks of voltage-independent regulation and did not involve PKC activation. A small fraction of the Oxo-M-induced CaV inhibition was diminished by a high concentration of Ca2+ chelator, whereas ≥50% of this inhibition was prevented by diC8-PIP2 dialysis. Localization of PIP2 in the plasma membrane was examined by transfecting INS-1 cells with PH-PLCδ1, which revealed a close temporal association between PIP2 hydrolysis and CaV channel inhibition. Furthermore, the depletion of PIP2 by a voltage-sensitive phosphatase reduced CaV currents in a way similar to that observed following M1R activation. These results indicate that activation of the M1R pathway inhibits the CaV channel via PIP2 depletion by a Ca2+-dependent mechanism in pancreatic ß- and INS-1 cells and thereby support the hypothesis that membrane phospholipids regulate ion channel activity by interacting with ion channels.

Voltage-Independent Inhibition of the Tetrodotoxin-Sensitive Sodium Currents by Oxotremorine and Angiotensin II in Rat Sympathetic Neurons.

Tetrodotoxin-sensitive Na(+) currents have been extensively studied because they play a major role in neuronal firing and bursting. In this study, we showed that voltage-dependent Na(+) currents are regulated in a slow manner by oxotremorine (oxo-M) and angiotensin II in rat sympathetic neurons. We found that these currents can be readily inhibited through a signaling pathway mediated by G proteins and phospholipase C (PLC) ß1. This inhibition is slowly established, pertussis toxin-insensitive, partially reversed within tens of seconds after oxo-M washout, and not relieved by a strong depolarization, suggesting a voltage-insensitive mechanism of inhibition. Specificity of the M1 receptor was tested by the MT-7 toxin. Activation and inactivation curves showed no shift in the voltage dependency under the inhibition by oxo-M. This inhibition is blocked by a PLC inhibitor (U73122, 1-(6-{[(17ß)-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino}hexyl)-1H-pyrrole-2,5-dione), and recovery from inhibition is prevented by wortmannin, a PI3/4 kinase inhibitor. Hence, the pathway involves Gq/11 and is mediated by a diffusible second messenger. Oxo-M inhibition is occluded by screening phosphatidylinositol 4,5-bisphosphate (PIP2)-negative charges with poly-l-lysine and prevented by intracellular dialysis with a PIP2 analog. In addition, bisindolylmaleimide I, a specific ATP-competitive protein kinase C (PKC) inhibitor, rules out that this inhibition may be mediated by this protein kinase. Furthermore, oxo-M-induced suppression of Na(+) currents remains unchanged when neurons are treated with calphostin C, a PKC inhibitor that targets the diacylglycerol-binding site of the kinase. These results support a general mechanism of Na(+) current inhibition that is widely present in excitable cells through modulation of ion channels by specific G protein-coupled receptors.

A Prospective, Comparative Study for the Evaluation of Postoperative Pain and Quality of Recovery in Patients Undergoing Robotic Versus Open Hysterectomy for Staging of Endometrial Cancer.

STUDY OBJECTIVE: To measure and compare postoperative pain and patient satisfaction in patients undergoing either robotic or open laparotomy for surgical staging of endometrial cancer. DESIGN: Prospective, comparative study (Canadian Task Force classification II). SETTING: University hospital. PATIENTS: A total of 142 patients undergoing either robotic or open laparotomy for surgical staging of endometrial cancer. INTERVENTIONS: Patients scheduled for surgical staging of endometrial cancer at a single institution were identified. The patients underwent either robotic or open hysterectomy for staging of endometrial cancer. The choice of operative approach (robotic vs laparotomy) was made by the faculty physician before enrollment. Patients participated in the study for up to 48 hours for pain assessments and up to 10 ± 3 days postoperatively for quality of recovery assessments. MEASUREMENTS AND MAIN RESULTS: The following measurements were performed: postoperative pain with the visual analog scale (VAS), 24-hour opioid consumption, and quality of recovery using the Quality of Recovery Questionnaire (QoR-40). The study was terminated owing to futility, given the lack of open procedures at our institution. Despite that lack of statistically significant difference between VAS scores at rest and with leg extension, there was a significant decrease in 24-hour opioid consumption in the robotic group. In addition, the QoR-40 showed an increased perception of recovery in patients within the robotic group compared with the laparotomy group. CONCLUSION: Patients with endometrial cancer who underwent robotic surgery had decreased postoperative opioid consumption and improved quality of recovery compared with those who underwent surgery via laparotomy.

Postoperative nausea and vomiting prophylaxis from an economic point of view.

Patients rank postoperative nausea and vomiting (PONV) in the top five most undesirable outcomes of surgery. Thirty percent of all surgical patients experience PONV. We conducted an economic study to determine the financial implications of providing surgical patients with PONV prophylaxis to increase patient satisfaction and minimize postoperative complications. Our main objective was to develop an economic model of PONV prophylaxis. We retrospectively reviewed all surgical cases who received care at our institution from June 2005 to June 2007 in which the surgical patient was billed for treatment of nausea and vomiting while in the hospital. The PONV risk factors for these patients were assessed as well as the revenue stream associated with those patients who returned to the hospital within 5 days with nausea and vomiting as their chief complaint. Of the total number of medical charts reviewed (56,532), 28 (1.57%) of 1783 patients who were billed for PONV while in the hospital returned to the hospital with PONV. The total billable charges for PONV for these returning patients were $83,674; the total reimbursements were $25,816 yielding a 31% reimbursement rate. The total hospital expenses were $24,123 yielding a net hospital profit of $1693 for treating these 28 patients. The average hospital cost and charge per antiemetic drug dose was $0.304 and $3.66, respectively. Using these figures, we determined that our hospital's net profit increases linearly with increased PONV prophylaxis administration. Our economic analysis shows that PONV prophylaxis is economically beneficial for the hospital when weighed against the expenses generated by treating patients returning to the hospital with PONV.

Current intraoperative devices to reduce visual loss after spine surgery.

Postoperative visual loss (POVL) after spine surgery performed with the patient prone is a rare but devastating postoperative complication. The incidence and the mechanisms of visual loss after surgery are difficult to determine. The 4 recognized causes of POVL are ischemic optic neuropathy (approximately 89%), central retinal artery occlusion (approximately 11%), cortical infarction, and external ocular injury. There are very limited guidelines or protocols on the perioperative practice for "prone-position" surgeries. However, new devices have been designed to prevent mechanical ocular compression during prone-position spine surgeries. The authors used PubMed to perform a literature search for devices used in prone-position spine surgeries. A total of 7 devices was found; the authors explored these devices' features, advantages, and disadvantages. The cause of POVL seems to be a multifactorial problem with unclear pathophysiological mechanisms. Therefore, ocular compression is a critical factor, and eliminating any obvious compression to the eye with these devices could possibly prevent this devastating perioperative complication.

Bempegaldesleukin plus Nivolumab in First-line Metastatic Urothelial Carcinoma: Results from PIVOT-02.

BACKGROUND: Despite recent changes in the treatment landscape, there remains an unmet need for effective, tolerable, chemotherapy-free treatments for patients with advanced/metastatic urothelial carcinoma (mUC), especially cisplatin-ineligible patients. OBJECTIVE: To evaluate the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab in patients with advanced/mUC from the phase 2 multicenter PIVOT-02 study. DESIGN, SETTING, AND PARTICIPANTS: This open-label, multicohort phase 1/2 study enrolled patients with previously untreated locally advanced/surgically unresectable or mUC (N = 41). INTERVENTION: Patients received BEMPEG 0.006 mg/kg plus nivolumab 360 mg intravenously every 3 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary objectives were safety and the objective response rate (ORR) in patients with measurable disease at baseline and at least one postbaseline tumor response assessment (response-evaluable). Secondary objectives were overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses via univariate logistic regression were performed to test the association between potential biomarkers (CD8+ tumor-infiltrating lymphocytes, tumor mutational burden, and IFN-γ gene expression profile) and response. RESULTS AND LIMITATIONS: The ORR was 35% (13/37 evaluable patients) and the complete response rate was 19% (7/37 patients); the median duration of response was not reached. Median PFS was 4.1 mo (95% confidence interval [CI] 2.1-8.7) and median OS was 23.7 mo (95% CI 15.8-not reached). Overall, 40/41 patients (98%) experienced at least one treatment-related adverse event (TRAE); grade 3/4 TRAEs occurred in 11 patients (27%), most commonly pyrexia (4.9%; 2 patients). Exploratory biomarker analyses showed no association between biomarkers and response. Limitations include the small sample size and single-arm design. CONCLUSIONS: BEMPEG plus nivolumab was well tolerated and showed antitumor activity as first-line treatment in patients with locally advanced/mUC. PATIENT SUMMARY: We investigated an immune-stimulating prodrug called bempegaldesleukin plus the antibody nivolumab as the first therapy for patients with advanced or metastatic cancer of the urinary tract. This combination had manageable treatment-related side effects and was effective in a subset of patients. This trial is registered at ClinicalTrials.gov as NCT02983045.

Bempegaldesleukin plus nivolumab in first-line renal cell carcinoma: results from the PIVOT-02 study.

BACKGROUND: Immune checkpoint inhibitor-based combinations have expanded the treatment options for patients with renal cell carcinoma (RCC); however, tolerability remains challenging. The aim of this study was to evaluate the safety and efficacy of the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) as first-line therapy in patients with advanced clear-cell RCC. METHODS: This was an open-label multicohort, multicenter, single-arm phase 1/2 study; here, we report results from the phase 1/2 first-line RCC cohort (N=49). Patients received BEMPEG 0.006 mg/kg plus NIVO 360 mg intravenously every 3 weeks. The primary objectives were safety and objective response rate (ORR; patients with measurable disease at baseline and at least one postbaseline tumor response assessment). Secondary objectives included overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses: association between baseline biomarkers and ORR. RESULTS: At a median follow-up of 32.7 months, the ORR was 34.7% (17/49 patients); 3/49 patients (6.1%) had a complete response. Of the 17 patients with response, 14 remained in response for >6 months, and 6 remained in response for >24 months. Median PFS was 7.7 months (95% CI 3.8 to 13.9), and median OS was not reached (95% CI 37.3 to not reached). Ninety-eight per cent (48/49) of patients experienced ≥1 treatment-related adverse event (TRAE) and 38.8% (19/49) had grade 3/4 TRAEs, most commonly syncope (8.2%; 4/49) and increased lipase (6.1%; 3/49). No association between exploratory biomarkers and ORR was observed. Limitations include the small sample size and single-arm design. CONCLUSIONS: BEMPEG plus NIVO showed preliminary antitumor activity as first-line therapy in patients with advanced clear-cell RCC and was well tolerated. These findings warrant further investigation.

Intraoperative MRI (ioMRI) in the setting of awake craniotomies for supratentorial glioma resection.

Both awake craniotomy under conscious sedation and use of intraoperative MRI can increase the efficiency and safety of glioma resections. In contrast to craniotomies under general anesthesia, neurosurgery under conscious sedation requires several changes to the routine operative setup when performed in the ioMRI environment. This work reports our experience with awake craniotomies under conscious sedation using ioMRI. Seven patients underwent awake-craniotomies for resection of supratentorial gliomas using ioMRI at the Ohio State University Medical Center and James Cancer Hospital by a single surgeon. ioMRI can be safely employed in patients who are undergoing craniotomies under conscious sedation. Particularly important is the evaluation by the anesthesiologist whether the patient is a good candidate to sustain a likely longer than average procedure in a setting where his active cooperation is not only required, but also the essential aspect of this procedure.

Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma.

PURPOSE: Therapies that produce deep and durable responses in patients with metastatic melanoma are needed. This phase II cohort from the international, single-arm PIVOT-02 study evaluated the CD122-preferential interleukin-2 pathway agonist bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) in first-line metastatic melanoma. METHODS: A total of 41 previously untreated patients with stage III/IV melanoma received BEMPEG 0.006 mg/kg plus NIVO 360 mg once every 3 weeks for ≤ 2 years; 38 were efficacy-evaluable (≥ 1 postbaseline scan). Primary end points were safety and objective response rate (blinded independent central review); other end points included progression-free survival, overall survival (OS), and exploratory biomarkers. RESULTS: At 29.0 months' median follow-up, the objective response rate was 52.6% (20 of 38 patients), and the complete response rate was 34.2% (13 of 38 patients). Median change in size of target lesions from baseline was -78.5% (response-evaluable population); 47.4% (18 of 38 patients) experienced complete clearance of target lesions. Median progression-free survival was 30.9 months (95% CI, 5.3 to not estimable). Median OS was not reached; the 24-month OS rate was 77.0% (95% CI, 60.4 to 87.3). Grade 3 and 4 treatment-related and immune-mediated adverse events occurred in 17.1% (7 of 41) and 4.9% (2 of 41) of patients, respectively. Increased polyfunctional responses in CD8+ and CD4+ T cells were seen in blood after treatment, driven by cytokines with effector functions. Early on-treatment blood biomarkers (CD8+ polyfunctional strength difference and eosinophils) correlated with treatment response. CONCLUSION: BEMPEG in combination with NIVO was tolerated, with relatively low rates of grade 3 and 4 treatment-related and immune-mediated adverse events. The combination had encouraging antitumor activity in first-line metastatic melanoma, including an extended median progression-free survival. Exploratory analyses associated noninvasive, on-treatment biomarkers with response, before radiologic evidence was observed.

SNAP II versus BIS VISTA monitor comparison during general anesthesia.

INTRODUCTION: Effectively monitoring the level of consciousness during general anesthesia is clinically beneficial to both the patient and the physician. An electroencephalogram (EEG)-based level-of-consciousness monitor can help minimize intraoperative awareness as well as the effects of over-sedation. In this study, we compared the SNAP II (Stryker Instruments, Kalamazoo, MI USA) and BIS VISTA (Aspect Medical Systems, Newton, MA USA) monitors' primary metrics (SI and BIS, respectively) in terms of correlation, agreement and responsiveness to return to preoperative baseline in surgical cases involving general anesthesia. METHODS: With institutional approval and written informed consent, 33 patients received general anesthesia with isoflurane while undergoing abdominal surgery. We attached both the SNAP II and BIS VISTA electrodes to each patient. We collected data from each monitor simultaneously and continuously, beginning just prior to induction and ending after extubation. Each monitor's level-of-consciousness index is a unit less metric that ranges from 0 to 100, with 100 indicating full consciousness. We performed a Bland-Altman and parameter difference analyses on the data. We calculated the time it took for each monitor to return to preoperative baseline level following cessation of anesthesia. We established an equivalence between the two indices over their entire range for our particular clinical scenario. RESULT: The indices were correlated (r = 0.736, P < 0.0001, N = 3,706 data point pairs). There was an overall difference between the two indices (median = 16.0, 25th/75th%ile = 10.0/21.1) with BIS lower than SI. A 40-60 BIS range (the typical target range during general anesthesia) was approximately equivalent to a 54-74 SI range. In all 33 subjects, SI reached baseline before BIS at the end of the case (median = 3.3 min, 25th/75th%ile = 1.6 min/8.2 min versus median = 8.9 min, 25th/75th = 3.7 min/14.5 min, P = 0.0200), even though both metrics were equal at the beginning of the case. DISCUSSION: Although the SI and BIS both can assess a patient's level of consciousness and are correlated, they are not in agreement with each other numerically and therefore are not interchangeable. It is difficult to assess each monitor's true responsiveness to acute changes in consciousness level from our study design. The differences between the metrics we observed in this study are most likely due to differences in signal processing methodologies, EEG frequencies employed and signal filtering utilized in the monitors.

Pregabalin in the reduction of pain and opioid consumption after burn injuries: A preliminary, randomized, double-blind, placebo-controlled study.

BACKGROUND: The primary objective of the study was to evaluate the efficacy of 300 milligrams (mg) and 600 mg of pregabalin compared to placebo in the reduction of pain in patients with noncritical partial and full thickness burn injuries. METHODS: A prospective, randomized, double-blinded, single center, placebo-controlled trial was conducted. Simple randomization method was used in this trial. After subjects met all the inclusion and none of the exclusion criteria, they were randomized and assigned to 1 of the 3 18-day treatments groups: Pregabalin 300 group, Pregabalin 600 group, or Placebo group. Demographics and clinical characteristics were recorded. The severity of pain was assessed by using the visual analog scale for pain intensity at baseline on day 3, day 9 ±â€Š3, day 25 ±â€Š7, day 90 ±â€Š6, and day 180 ±â€Š12. RESULTS: A total of 54 subjects were randomly assigned, and 51 were included in the data analysis. Demographics and clinical characteristics did not differ significantly between the 3 groups. There was a statistically significant difference in pain between the Pregabalin 300 and Pregabalin 600 groups (P-value = .0260). The Pregabalin 300 group had 17.93 units (95% confidence interval: 1.83-34.04) higher pain scores on average than the Pregabalin 600 group, regardless of time. The adjusted P-value comparing 0 to 300 was .1618, while the adjusted P-value for 0 versus 600 was .5304. There was an overall difference in pain across time regardless of study group (P-value = <.0001). An overall difference in opioid consumption (P-value = .0003) and BSHS (P-value = .0013) across time regardless of study group was noted. CONCLUSIONS: Pregabalin could be part of a promising multimodal analgesic regimen in noncritical burn population. Future placebo-controlled studies assessing the use of pregabalin in burn victim patients may further endorse our findings.

A Prospective, Multicenter, Single-Blind Study Assessing Indices of SNAP II Versus BIS VISTA on Surgical Patients Undergoing General Anesthesia.

BACKGROUND: Traditionally, anesthesiologists have relied on nonspecific subjective and objective physical signs to assess patients' comfort level and depth of anesthesia. Commercial development of electrical monitors, which use low- and high-frequency electroencephalogram (EEG) signals, have been developed to enhance the assessment of patients' level of consciousness. Multiple studies have shown that monitoring patients' consciousness levels can help in reducing drug consumption, anesthesia-related adverse events, and recovery time. This clinical study will provide information by simultaneously comparing the performance of the SNAP II (a single-channel EEG device) and the bispectral index (BIS) VISTA (a dual-channel EEG device) by assessing their efficacy in monitoring different anesthetic states in patients undergoing general anesthesia. OBJECTIVE: The primary objective of this study is to establish the range of index values for the SNAP II corresponding to each anesthetic state (preinduction, loss of response, maintenance, first purposeful response, and extubation). The secondary objectives will assess the range of index values for BIS VISTA corresponding to each anesthetic state compared to published BIS VISTA range information, and estimate the area under the curve, sensitivity, and specificity for both devices. METHODS: This is a multicenter, prospective, double-arm, parallel assignment, single-blind study involving patients undergoing elective surgery that requires general anesthesia. The study will include 40 patients and will be conducted at the following sites: The Ohio State University Medical Center (Columbus, OH); Northwestern University Prentice Women's Hospital (Chicago, IL); and University of Miami Jackson Memorial Hospital (Miami, FL). The study will assess the predictive value of SNAP II versus BIS VISTA indices at various anesthetic states in patients undergoing general anesthesia (preinduction, loss of response, maintenance, first purposeful response, and extubation). The SNAP II and BIS VISTA electrode arrays will be placed on the patient's forehead on opposite sides. The hemisphere location for both devices' electrodes will be equally alternated among the patient population. The index values for both devices will be recorded and correlated with the scorings received by performing the Modified Observer's Assessment of Alertness and Sedation and the American Society of Anesthesiologists Continuum of Depth of Sedation, at different stages of anesthesia. RESULTS: Enrollment for this study has been completed and statistical data analyses are currently underway. CONCLUSIONS: The results of this trial will provide information that will simultaneously compare the performance of SNAP II and BIS VISTA devices, with regards to monitoring different anesthesia states among patients. CLINICALTRIAL: Clinicaltrials.gov NCT00829803; https://clinicaltrials.gov/ct2/show/NCT00829803 (Archived by WebCite at http://www.webcitation.org/6nmyi8YKO).

The Effect of a Combination Treatment Using Palonosetron, Promethazine, and Dexamethasone on the Prophylaxis of Postoperative Nausea and Vomiting and QTc Interval Duration in Patients Undergoing Craniotomy under General Anesthesia: A Pilot Study.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is a displeasing experience that distresses surgical patients during the first 24 h after a surgical procedure. The incidence of postoperative nausea occurs in about 50%, the incidence of postoperative vomiting is about 30%, and in high-risk patients, the PONV rate could be as high as 80%. Therefore, the study design of this single arm, non-randomized, pilot study assessed the efficacy and safety profile of a triple therapy combination with palonosetron, dexamethasone, and promethazine to prevent PONV in patients undergoing craniotomies under general anesthesia. METHODS: The research protocol was approved by the institutional review board and 40 subjects were provided written informed consent. At induction of anesthesia, a triple therapy of palonosetron 0.075 mg IV, dexamethasone 10 mg IV, and promethazine 25 mg IV was given as PONV prophylaxis. After surgery, subjects were transferred to the surgical intensive care unit or post anesthesia care unit as clinically indicated. Ondansetron 4 mg IV was administered as primary rescue medication to subjects with PONV symptoms. PONV was assessed and collected every 24 h for 5 days via direct interview and/or medical charts review. RESULTS: The overall incidence of PONV during the first 24 h after surgery was 30% (n = 12). The incidence of nausea and emesis 24 h after surgery was 30% (n = 12) and 7.5% (n = 3), respectively. The mean time to first emetic episode, first rescue, and first significant nausea was 31.3 (±33.6), 15.1 (±25.8), and 21.1 (±25.4) hours, respectively. The overall incidence of nausea and vomiting after 24-120 h period after surgery was 30% (n = 12). The percentage of subjects without emesis episodes over 24-120 h postoperatively was 70% (n = 28). No subjects presented a prolonged QTc interval ≥500 ms before and/or after surgery. CONCLUSION: Our data demonstrated that this triple therapy regimen may be an adequate alternative regimen for the treatment of PONV in patients undergoing neurological surgery under general anesthesia. More studies with a control group should be performed to demonstrate the efficacy of this regimen and that palonosetron is a low risk for QTc prolongation. CLINICALTRIALSGOV IDENTIFIER: NCT02635828 (https://clinicaltrials.gov/show/NCT02635828).

A Prospective, Randomized, Double-Blinded, Double-Dummy Pilot Study to Assess the Preemptive Effect of Triple Therapy with Aprepitant, Dexamethasone, and Promethazine versus Ondansetron, Dexamethasone and Promethazine on Reducing the Incidence of Postoperative Nausea and Vomiting Experienced by Patients Undergoing Craniotomy Under General Anesthesia.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is among the most common distressing complications of surgery under anesthesia. Previous studies have demonstrated that patients who undergo craniotomy have incidences of nausea and vomiting as high as 50-70%. The main purpose of this pilot study is to assess the incidence of PONV by using two different prophylactic regimens in subjects undergoing a craniotomy. Thus, we designed this study to assess the efficacy and safety of triple therapy with the combination of dexamethasone, promethazine, and aprepitant versus ondansetron to reduce the incidence of PONV in patients undergoing craniotomy. MATERIALS AND METHODS: This is a prospective, single center, two-armed, randomized, double-dummy, double-blind, pilot study. Subjects were randomly assigned to one of the two treatment groups. Subjects received 40 mg of aprepitant pill (or matching placebo pill) 30-60 min before induction of anesthesia and 4 mg of ondansetron IV (or 2 ml of placebo saline solution) at induction of anesthesia. In addition, all subjects received 25 mg of promethazine IV and 10 mg of dexamethasone IV at induction of anesthesia. Assessments of PONV commenced for the first 24 h after surgery and were subsequently assessed for up to 5 days. RESULTS: The overall incidence of PONV during the first 24 h after surgery was 31.0% (n = 15) in the aprepitant group and 36.2% (n = 17) for the ondansetron group. The median times to first emetic and significant nausea episodes were 7.6 (2.9, 48.7) and 14.3 (4.4, 30.7) hours, respectively, for the aprepitant group and 6.0 (2.2, 29.5) and 9.6 (0.7, 35.2) hours, respectively, for the ondansetron group. There were no statistically significant differences between these groups. No adverse events directly related to study medications were found. CONCLUSION: This pilot study showed similar effectiveness when comparing the two PONV prophylaxis regimens. Our data showed that both treatments could be effective regimens to prevent PONV in patients undergoing craniotomy under general anesthesia. Future trials testing new PONV prophylaxis regimens in this surgical population should be performed to gain a better understanding of how to best provide prophylactic treatment.

BMI as a Predictor for Potential Difficult Tracheal Intubation in Males.

INTRODUCTION: Difficult tracheal intubation is a common source of mortality and morbidity in surgical and critical care settings. The incidence reported of difficult tracheal intubation is 0.1%-13% and reaches 14% in the obese population. The objective of our retrospective study was to investigate and compare the utility of body mass index (BMI) as indicator of difficult tracheal intubation in males and females. MATERIAL AND METHODS: We performed a retrospective chart review of patients who underwent abdominal surgeries with American Society of Anesthesiologists I to V under general anesthesia requiring endotracheal intubation. The following information was obtained from medical records for analysis: gender, age, height, weight, BMI, length of patient stay in the Post Anesthesia Care Unit, past medical history of sleep apnea, Mallampati score, and the American Society of Anesthesiologists classification assigned by the anesthesia care provider performing the endotracheal intubation. RESULTS: Of 4303 adult patients, 1970 (45.8%) men and 2333 (54.2%) women were enrolled in the study. Within this group, a total of 1673 (38.9%) patients were morbidly obese. The average age of the study group was 51.4 ± 15.8 and the average BMI was 29.7 ± 8.2 kg/m(2). The overall incidence of the encountered difficult intubations was 5.23% or 225 subjects. Thus, our results indicate that BMI is a reliable predictor of difficult tracheal intubation predominantly in the male population; another strong predictor, with a positive linear correlation, being the Mallampati score. CONCLUSION: In conclusion, our data shows that BMI is a reliable indicator of potential difficult tracheal intubation only in male surgical patients.

In vitro assessment of clevidipine using the profilin1 hypertensive mouse model.

Hypertension represents a major risk factor for cardiovascular events, associating with vascular hypertrophy and dysfunction in resistance vessels. Clevidipine is a novel antihypertensive drug working as a selective calcium channel antagonist with an ultra-short half-life that lowers arterial blood pressure by reducing systemic arterial resistance. The aim was to assess the effect of clevidipine on the hypertrophic vessels of profilin1 hypertensive transgenic mice compared to sodium nitroprusside (SNP) and labetalol using wire myograph techniques. The effects of clevidipine, SNP and labetalol on the hypertrophic vessels were studied on mesenteric arterial function from 8 profilin1 hypertrophic mice and eight non-transgenic controls. Our results showed a significant difference between the effects of the three drugs on the hypertrophic mesenteric arteries of transgenic profilin1 mice compared to the non-transgenic controls. The half maximal effective concentration (EC50) of clevidipine, SNP and labetalol in profilin1 mice (1.90 ± 0.05, 0.97 ± 0.07, 2.80 ± 0.05 nM, respectively) were significantly higher than the EC50 in non-transgenic controls (0.91 ± 0.06, 0.32 ± 0.06, 0.80 ± 0.09 nM, respectively). Moreover, the increase in the EC50 for clevidipine (2-fold) to produce the same effect on both normal and hypertrophic arteries was less than that of SNP (3-fold) and labetalol (3.5-fold). Therefore, we concluded clevidipine exhibited the lowest dose shift to relax the hypertrophic vessels compared to SNP and labetalol in the profilin1 hypertrophic animal mouse model.

A retrospective cohort-matched comparison of conscious sedation versus general anesthesia for supratentorial glioma resection. Clinical article.

OBJECT: Glioma resection under conscious ("awake") sedation (CS) is used for eloquent areas of the brain to minimize postoperative neurological deficits. The objective of this study was to compare the duration of hospital stay, overall hospital cost, perioperative morbidity, and postoperative patient functional status in patients whose gliomas were resected using CS versus general endotracheal anesthesia (GEA). METHODS: Twenty-two cases in 20 patients who underwent surgery for cerebral gliomas under CS and a matched cohort of 22 cases in 19 patients who underwent surgery under GEA over a 3-year period were retrospectively evaluated. Criteria for inclusion in the study were as follows: 1) a single cerebral lesion; 2) gross-total resection as evidenced by postoperative Gd-enhanced MR imaging within 48 hours of surgery; 3) a WHO Grade II, III, or IV glioma; 4) a supratentorial lesion location; 5) a Karnofsky Performance Scale score ≥ 70; 6) an operation performed by the same neurosurgeon; and 7) an elective procedure. RESULTS: The average hospital stay was significantly different between the 2 groups: 3.5 days for patients who underwent CS and 4.6 days for those who underwent GEA. This result translated into a significant decrease in the average inpatient cost after intensive care unit (ICU) care for the CS group compared with the GEA group. Other variables were not significantly different. CONCLUSIONS: Patients undergoing glioma resection using CS techniques have a significantly shorter hospital stay with reduced inpatient hospital expenses after postoperative ICU care.

Clevidipine butyrate: a promising new drug for the management of acute hypertension.

Clevidipine butyrate is an ultrashort-acting intravenous dihydropyridine calcium-channel blocker that has been approved by the FDA for the reduction of blood pressure when oral therapy is not feasible. Hypertension is a global disease that affects more than 1 billion people worldwide and 75 million people in the USA. There are multiple agents available for the management of hypertension. The acute setting is where the challenge arises for developing new agents that not only decrease, but more importantly, optimally control blood pressure. Many drugs lower blood pressure; however, only a few have the capacity to precisely control hypertension in the acute phase. Clevidipine has unique pharmacodynamic and pharmacokinetic properties that enable the fast, safe and adequate reduction of blood pressure in hypertensive emergencies, with unique precision necessary to maintain the target blood pressure range. Its use in different clinical settings has been evaluated in several Phase I, II and III clinical studies. It is easily administered and titrated with minimal side effects, achieves fast control with low doses, is highly successful as monotherapy and allows excellent transition to oral medication. Thus, clevidipine is a promising new agent for the management of acute hypertension in a variety of clinical settings.

Anesthesia in the intraoperative MRI environment.

Intraoperative MRI (iMRI) can be applied in several surgical settings. The incorporation of MRI technology into the operating room requires special considerations. The size and design of the operating room, including the equipment introduced into this setting, must be MR safe and allow adequate anesthesia monitoring and care. There are general restrictions and perils that may present in an operating room setting because of the MRI technology involving the monitoring equipment, anesthesia machine, and infusion devices. Incorporating the MRI technology into the operating room presents a new challenge in a transdisciplinary environment. The use of the iMRI technology has provided revolutionary tools for the new generation of medical practice.