Alex Y. Bekker, M.D., Ph.D.

A Randomized Double Blind Study to Evaluate Efficacy of Palonosetron With Dexamethasone Versus Palonosetron Alone for Prevention of Postoperative and Postdischarge Nausea and Vomiting in Subjects Undergoing Laparoscopic Surgeries with High Emetogenic Risk
Blitz JD; Haile M; Kline R; Franco L; Didehvar S; Pachter HL; Newman E; Bekker A
2011 Apr 23;:?-?, American journal of therapeutics
Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) are common occurrences (50%-80%) after laparoscopic surgery. Palonosetron (Pal), the newest 5-HT3 antagonist, is an effective antiemetic that has advantages in treating PDNV due to its prolonged duration of action. We hypothesized that a combination of Pal and dexamethazone (Dex) could further improve the efficacy of the treatment in comparison to Pal alone in patients at high risk for PONV. Patients scheduled to undergo laparoscopic surgeries under general anesthesia were randomized to receive 8-mg dexamethasone + 0.075-mg palonosetron (Pal + Dex) or an equivalent volume of saline + 0.075 mg palonosetron (Pal). Data was collected at defined postoperative times (2, 6, 12, 24, and 72 hours). All patients also completed an 18-question QOL-Functional Living Index-Emesis instrument at 96 hours. We enrolled 118 patients, ASA 1-2, with at least 3 PONV risk factors, who were undergoing outpatient surgery. Both groups had a low incidence of vomiting in the PACU (Pal + Dex, 1.7%; Pal, 6.8%) and at 72 hours (0.0% both groups). Complete response (no vomiting, no rescue medication) was not different between treatment groups for any time intervals. Cumulative success rates over the entire 72 hours were 60.4% (Pal + Dex) versus 60.0% (Pal). The Pal + Dex group showed a trend toward greater satisfaction on the QOL- Functional Living Index-Emesis scores with the greatest differences in the 'nausea domain'. The combination therapy of palonosetron + dexamethasone did not reduce the incidence of PONV or PDNV when compared with palonosetron alone. There was no change in comparative efficacy over 72 hours, most likely due to the low incidence of PDNV in both groups
— id: 142016, year: 2011, vol: , page: ?, stat: Journal Article,

A Randomized, Open-Label Study of the Safety and Tolerability of Fospropofol for Patients Requiring Intubation and Mechanical Ventilation in the Intensive Care Unit
Candiotti, Keith A.; Gan, Tong J.; Young, Christopher; Bekker, Alex; Sum-Ping, S. T. John; Kahn, Richard; Lebowitz, Philip; Littman, Jeffrey J.
2011 SEP ;113(3):550-556, Anesthesia & analgesia
BACKGROUND: Current drugs for induction and maintenance of sedation in mechanically ventilated patients in the intensive care unit have limitations. Fospropofol, a prodrug of propofol, has not been studied as a sedative in the ICU setting. METHODS: In this randomized, open-label pilot study, patients received 1 of 3 regimens with a goal of maintaining a Ramsay Sedation Score of 2 to 5: (1) fospropofol IV infusion with a bolus and increased infusion rate for agitation events (infusion/bolus); (2) fospropofol IV infusion with an increased infusion rate for agitation events (infusion only); or (3) propofol IV infusion with an increased infusion rate for agitation events. RESULTS: Sixty patients received study drug and were included in the safety and efficacy analyses. Because incidence rates for adverse events were similar between fospropofol groups, and because the study was not powered to determine significant differences between treatment groups for safety variables, adverse events for both fospropofol groups were combined. In the fospropofol groups, 28 out of 38 patients (74%) experienced treatment-emergent adverse events in comparison with 14 out of 22 patients (64%) in the propofol group. The most common treatment-emergent adverse events with fospropofol were procedural pain (21.1%) and nausea (13.2%). Two patients (1 each in the fospropofol infusion/bolus and the propofol groups) experienced hypotension during the study as a potential sedation-related adverse event. Mean plasma formate levels were not significantly different among groups. Patients in all 3 treatment groups maintained Ramsay Sedation Scores of 2 to 5 for > 90% of the time they were sedated. CONCLUSION: This pilot study suggests that fospropofol, administered in either an infusion/bolus or infusion-only regimen, is tolerable and effective for short-term induction and maintenance of sedation in mechanically ventilated intensive care unit patients. (Anesth Analg 2011; 113: 550-6)
— id: 137028, year: 2011, vol: 113, page: 550, stat: Journal Article,

Hippocampus cytokine expression following acute hypotension and anti-inflammatory treatment in adult mice
Garcia E.A.; Haile M.M.; Galoyan S.; Kline R.P.; Bekker A.Y.
2011 ;112(5 SUPPL 1):?-?, Anesthesia & analgesia
Introduction : Hypotension has been implicated in the development of cognitive dysfunction (CD). Nitroglycerin induced hypotension (NTG-IH) to below the range of cerebral autoregulation causes a transient impairment of short-term memory in mice that is ameliorated by NSAID Meloxicam (MEL) given at 24h.1 Memory was found intact on Day 1, impaired on Day 5, and intact on Day 9. We tested the hypothesis that changes in hippocampal cytokine levels would be associated with CD. Methods : After IACUC approval, 45 Swiss-Webster, 30-40g mice (6-8 weeks) were randomized into 9 groups: 1) no treatment; 2) i.p. NTG(60 mg/kg) tested at 8h; 3) at 24h; 4) at 72h; 5) on D5; 6) on D7; 7) on D9; 8) NTG then i.p. MEL (60mg/kg) at 24h tested at 72h ; 9) NTG then MEL at 24h tested on D5. Under ketamine/ xylazine anesthesia, hippocampi were isolated and prepared for analysis.2 Hippocampal saturation of TNF-alpha, INF-, IL-1alpha, IL-1beta, IL-2, IL-6, & IL-10 was determined by ELISA with MILLIPLEX Multi-Analyte Profiling. Data was analyzed using Kruskal- Wallis One-Way ANOVA and Mann-Whitney post-hoc tests with Bonferonni correction. Results : After adjustment for outliers, 1 sample each from groups 4, 5, and 7 were excluded. A time course analysis of cytokine expression after NTG-IH showed a steady, progressive increase of IL-1beta & IL-2 expression in the first 72h after which cytokines stabilize and remain elevated through D9. All IL-1beta & IL-2 points were significant against baseline (p < .0167) except for IL-1beta at 8h and 72h, and IL-2 at 72h (Fig 1). No significant changes were observed in TNF-alpha, INF-, IL-1alpha, or IL-6 at any time. The MEL group showed elevated expression of 1L-1beta & IL-2 at 120h vs. baseline (p < .0167) but did not differ from NTG at 120h (Fig 2). At 72h the MEL group exhibited an attenuation of 1L-1beta that did not differ from baseline, but was significantly different from NTG at 72h (p < .0167). 1L-2 also showed trends of attenuation although no statistical significance was observed (Fig 3). Discussion : CNS inflammation and cytokine expression have been implicated in the development of CD.3 NTG-IH exacerbates the expression of IL-1beta & IL-2 in murine hippocampus, which peaks at 72h and stabilizes thereafter. Intervention with NSAID Meloxicam at 24h attenuates this response at 72h, but does not significantly alter expression on D5 when compared to NTG. This suggests that short-term memory function is not cytokinedependent, but rather that there are secondary mechanisms sensitive to cytokine modulation which may be involved with cognition in the setting of inflammation. (Graph presented)
— id: 146279, year: 2011, vol: 112, page: ?, stat: Journal Article,

Effects of surgery on cortical atrophy
Kline R.; Pirraglia E.; Cheng H.; Li Y.; Haile M.; De Leon M.; Bekker A.
2011 ;7(4 SUPPL 1):S3-S3, Alzheimer's & Dementia
Background: There have been numerous reports of acute and delayed impairment of neurocognitive performance following surgery. Structural MRI has been used to successfully diagnose and monitor Alzheimer's disease, and is here applied to examine the impact of surgery on baseline atrophy in elderly patients. We compared changes in cortical anatomy for defined inter-visit intervals between a surgical cohort and a frequency matched non-surgical control. Methods: Data was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (www.loni.ucla.edu/ADNI), and included subjects either cognitively normal (NL) or diagnosed with mild cognitive impairment (MCI), and who did not progress. Ages are from 55 through 90, with minimum 6 grades of education. Putative surgical patients were selected by searching the comment fields for positive key words (e.g. surgery, thoracotomy, operative etc.) and then screening manually for confirmation. The final cohort contained 32 subjects and 79 non-surgical subjects, frequency matched by follow up time. Repeated Measures ANCOVA was used to evaluate the change in bilateral grey (GM) and white matter (WM) volume, before and after surgery, or between the last two evaluations for non-surgery group. Covariants included intracranial volume, age, and months to follow-up evaluation with diagnostic group (NL or MCI) a cofactor. Statistical significance was p < 0.05 (SPSS version 18.0; Chicago, IL). Results: Examining GM volume (left hemisphere), the 3-way interaction of evaluation, diagnosis, and surgery was significant (F1,104 =6.4, p<.05) indicating that slopes were different depending on diagnostic group; where MCI with surgery showed a significantly greater decrease inGMvolume compared toMCIwithout surgery (F1,47=7.9, p<.01); no significant difference for NL. Examining GM (right hemisphere), the 3-way interaction was not significant, but there was a significant decrease in GM volume (F1,105 =4.1, p<.05) for surgery compared to non-surgery subjects. No significant differences found for WM volume. Conclusions: In our cohort of elderly subjects, surgery resulted in amore pronounced GMvolume atrophy than seen in non-surgical subjects, with MCI subjects at higher risk. An examination of neurocognitive effects of surgery, in progress, suggests a correlation between atrophy and function
— id: 136976, year: 2011, vol: 7, page: S3, stat: Journal Article,

Transient Effects of Anesthetics on Dendritic Spines and Filopodia in the Living Mouse Cortex
Yang G; Chang PC; Bekker A; Blanck TJ; Gan WB
2011 Oct;115(4):718-726, Anesthesiology
BACKGROUND:: Anesthetics are widely used to induce unconsciousness, pain relief, and immobility during surgery. It remains unclear whether the use of anesthetics has significant and long-lasting effects on synapse development and plasticity in the brain. To address this question, the authors examined the formation and elimination of dendritic spines, postsynaptic sites of excitatory synapses, in the developing mouse cortex during and after anesthetics exposure. METHODS:: Transgenic mice expressing yellow fluorescence protein in layer 5 pyramidal neurons were used in this study. Mice at 1 month of age underwent ketamine-xylazine and isoflurane anesthesia over a period of hours. The elimination and formation rates of dendritic spines and filopodia, the precursors of spines, were followed over hours to days in the primary somatosensory cortex using transcranial two-photon microscopy. Four to five animals were examined under each experimental condition. Student t test and Mann-Whitney U test were used to analyze the data. RESULTS:: Administration of either ketamine-xylazine or isoflurane rapidly altered dendritic filopodial dynamics but had no significant effects on spine dynamics. Ketamine-xylazine increased filopodial formation whereas isoflurane decreased filopodial elimination during 4 h of anesthesia. Both effects were transient and disappeared within a day after the animals woke up. CONCLUSION:: Studies suggest that exposure to anesthetics transiently affects the dynamics of dendritic filopodia but has no significant effect on dendritic spine development and plasticity in the cortex of 1-month-old mice
— id: 137134, year: 2011, vol: 115, page: 718, stat: Journal Article,

Efficacy of Clevidipine in Controlling Perioperative Hypertension in Neurosurgical Patients: Initial Single-center Experience
Bekker, Alex; Didehvar, Sorosch; Kim, Sunmi; Golfinos, John G; Parker, Erik; Sapson, Andrew; Haile, Michael; Kline, Richard; Lee, Mitchell
2010 Oct;22(4):330-335, Journal of neurosurgical anesthesiology
BACKGROUND: Acute blood pressure (BP) elevations in neurosurgical patients are associated with serious neurologic, cardiovascular, or surgical site complications. Clevidipine, an ultra-short-acting dihydropyridine calcium antagonist, has been shown to be efficacious and safe for acute hypertension in cardiac surgery. This study assessed the efficacy and safety of clevidipine in controlling perioperative hypertension in the neurosurgical setting. METHODS: Patients scheduled for intracranial surgery were prospectively enrolled after giving consent. Clevidipine (0.5 mg/mL in 20% lipid solution, which was to be initiated at 10 mg/h and titrated to effect) was administered as the primary antihypertensive agent for perioperative hypertension, with target BPs of less than 130 mm Hg. Other vasoactive drugs were administered as needed for treating systolic BP (SBP) less than 90 mm Hg or greater than 130 mm Hg. The primary study endpoint was the proportion of patients not requiring rescue antihypertensives to maintain target SBP (<130 mm Hg). RESULTS: Twenty-two patients were enrolled. One patient did not require antihypertensive therapy. Seventeen patients (17 of 21, 81%) were treated with clevidipine alone; one received clevidipine in the postanesthesia care unit only. Twenty-eight hypertensive episodes (defined as any new acute BP elevation requiring clevidipine initiation) were documented. SBP was reduced to target level within 15 minutes in 22 of 28 episodes (78.6%). Two mild hypotensive episodes occurred after the initiation of clevidipine infusion; these transient decreases in BP were treated with vasoactive drugs and resolved within 5 minutes. CONCLUSIONS: Clevidipine is effective and safe for perioperative hypertension in patients undergoing intracranial procedures. Rapid control of BP is possible with higher starting doses. Drug effects resolved rapidly after drug discontinuation
— id: 112425, year: 2010, vol: 22, page: 330, stat: Journal Article,

Does mild cognitive impairment increase the risk of developing postoperative cognitive dysfunction?
Bekker, Alex; Lee, Cynthia; de Santi, Susan; Pirraglia, Elizabeth; Zaslavsky, Alexander; Farber, Sonya; Haile, Michael; de Leon, Mony J
2010 Jun;199(6):782-788, American journal of surgery
BACKGROUND: Increasingly, postoperative cognitive dysfunction (POCD) is recognized as a complication after surgery in the elderly. We sought to determine whether patients with mild cognitive impairment (MCI) would have an accelerated progression of dementia postoperatively when compared with the patients without MCI. METHODS: The Center for Brain Health at the New York University (NYU) Medical Center maintains records of volunteers who undergo a series of neurological assessments. We reviewed records of 670 patients who received at least 2 evaluations and whose surgery occurred before the second assessment. Longitudinal differences of several cognitive domains were examined. RESULTS: Individuals with MCI and surgery had a greater decline in performance on the Digit Span Forward test compared with those with MCI without surgery on their postoperative evaluation (F(3,158) = 3.12, P = .03). No performance changes were detected in the normal subjects. CONCLUSION: These preliminary findings suggest that surgery negatively impacts attention/concentration in patients with MCI but not in normal individuals. This is the first study that identified a specific subgroup of patients who are predisposed to POCD
— id: 110877, year: 2010, vol: 199, page: 782, stat: Journal Article,

A Phase IIIb, Randomized, Double-blind, Placebo-controlled, Multicenter Study Evaluating the Safety and Efficacy of Dexmedetomidine for Sedation During Awake Fiberoptic Intubation
Bergese, Sergio D; Candiotti, Keith A; Bokesch, Paula M; Zura, Andrew; Wisemandle, Wayne; Bekker, Alex Y
2010 Nov-Dec;17(6):586-595, American journal of therapeutics
GABA-mediated sedatives have respiratory depressant properties that may be detrimental in patients with difficult airways. In this randomized, double-blind, multicenter, Phase IIIb Food and Drug Administration study, safety and efficacy of dexmedetomidine compared with placebo were evaluated as the primary sedative for awake fiberoptic intubation (AFOI). Patients were randomized to receive dexmedetomidine or saline. Patients were sedated with dexmedetomidine or rescue midazolam to achieve targeted sedation (Ramsay Sedation Scale >/= 2) before topicalization and throughout AFOI. Primary efficacy endpoint was percentage of patients requiring rescue midazolam; secondary efficacy endpoints were total dose of rescue midazolam, percentage requiring additional rescue nonmidazolam medications, anesthesiologist's assessment of ease of subject care, and patient recall and satisfaction 24 hours postoperatively. Less rescue midazolam was required to maintain Ramsay Sedation Scale >/=2 (47.3% vs. 86.0%, P < 0.001), and supplemental midazolam dose was lower (1.07 +/- 1.5 mg vs. 2.85 +/- 3.0 mg, P < 0.001) with dexmedetomidine compared with placebo. More Mallampati Class IV patients treated with dexmedetomidine were successfully intubated without midazolam than with placebo (66.7% vs. 8.3%, P = 0.009). Dexmedetomidine decreased blood pressure and heart rate compared with placebo patients sedated with midazolam. Patients and anesthesiologists showed favorable satisfaction responses in both groups. Adverse events and patient recall were similar in both groups. Dexmedetomidine is effective as the primary sedative in patients undergoing AFOI. Some patients may require small supplemental doses of midazolam, in addition to dexmedetomidine, to achieve sufficient sedation for AFOI. Dexmedetomidine provides another AFOI option for sedation of patients with difficult airways
— id: 114168, year: 2010, vol: 17, page: 586, stat: Journal Article,

Safety and tolerability of fospropofol for patients requiring intubation and mechanical ventilation in the ICU: Randomized, open-label study vs propofol
Candiotti K.; Gan T.; Bekker A.; Sum-Ping S.T.; Kahn R.; Lebowitz P.; Littman J.
2010 ;38:A249-A249, Critical care medicine
Introduction: Patients who are intubated and ventilated in ICU settings often experience agitation and demonstrate excessive stress responses. Hypothesis: We hypothesized that fospropofol, a prodrug of propofol, can be administered safely with minimal adverse eventswhenusedto induce sedation in these patients.Methods:Thesafetyandtolerability of intravenous (IV) infusions of fospropofol compared with IV propofol were evaluated in this randomized, open-label study in adult patients requiring short-term sedation in an ICU. Patients with ASA status P1 to P4 who were expected to require 2 to 12 hours of mechanical ventilation while under sedation in an ICU were randomized to 1 of 3 treatments designed to maintain a Ramsay Sedation Score (RSS) of 2 to 5: (1) continuous IV fospropofol infusion (25 mu g/kg * min-1) with a bolus and increased infusion rate for agitation events (infusion/bolus group); (2) IV fospropofol infusion (25mu g/kg* min-1) with an increased infusion rate for agitation events (infusion-only group); and (3) IV propofol infusion (25mu g/kg * min-1) with an increased infusion rate for agitation events (propofol group). Results: Of the 60 enrollees, 18, 20, and 22 were randomized to each treatment group, respectively.Meaninfusion rates were 52.0 to 76.2mu g/kg * min-1 for the fospropofol infusion/bolus group, 42.1 to 54.6mu g/kg * min-1for the fospropofol infusiononly group, and 18.9 to 31.6mu g/kg * min-1 for the propofol group. The most frequently occurring adverse events in the 2 fospropofol groups combined compared with the propofol group, respectively, were procedural pain (21.1% vs 9.1%), hyperglycemia (5.3% vs 13.6%), and nausea (13.2% vs 4.5%), and the largest mean decreases in systolic blood pressure were -13.1 and -14.2mmHg, respectively.Twopatients (1 each in the fospropofol infusion/bolus group and the propofol group) experienced hypotension during the study. Mean plasma formate levels were not significantly different between groups. On average, RSS scores for each test group were within 2 to 5 for > 90% of the time the patients were sedated. Conclusions: Fospropofol is tolerable when used for short-term induction and maintenance of sedation in mechanically ventilated ICU patients
— id: 117361, year: 2010, vol: 38, page: A249, stat: Journal Article,

Monitored anesthesia care with dexmedetomidine: a prospective, randomized, double-blind, multicenter trial
Candiotti, Keith A; Bergese, Sergio D; Bokesch, Paula M; Feldman, Marc A; Wisemandle, Wayne; Bekker, Alex Y
2010 Jan;110(1):47-56, Anesthesia & analgesia
BACKGROUND: Dexmedetomidine (DEX) is increasingly being used as a sedative for monitored anesthesia care (MAC) because of its analgesic properties, 'cooperative sedation,' and lack of respiratory depression. In this randomized, multicenter, double-blind, Phase III Food and Drug Administration study, we evaluated the safety and efficacy of two doses of DEX for sedation of patients undergoing a broad range of surgical or diagnostic procedures requiring MAC. METHODS: Three hundred twenty-six patients were randomized 2:2:1 to DEX 0.5 microg/kg, DEX 1 microg/kg, or saline placebo initial loading dose, followed by a maintenance infusion of 0.2-1.0 microg x kg(-1) x h(-1) of DEX (or equivalent volume of saline) titrated to a targeted level of sedation (< or = 4 on the Observer's Assessment of Alertness/Sedation Scale [OAA/S]). Study drug was started at least 15 min before placement of regional or local anesthetic block. Midazolam was given for OAA/S > 4 and fentanyl for pain. The primary end-point was the percentage of patients not requiring rescue midazolam. RESULTS: Significantly fewer patients in the 0.5- and 1-microg/kg DEX groups required supplemental midazolam compared with placebo (59.7% [80/134], 45.7% [59/129] vs 96.8% [61/63], respectively; P < 0.001) and at lower doses to achieve an OAA/S < or = 4 before and during surgery compared with the saline group (1.4 and 0.9 mg vs 4.1 mg, respectively; P < 0.001, each group compared with placebo). Both DEX groups required significantly less fentanyl (84.8 and 83.6 microg vs 144.4 microg, respectively; P < 0.001, for both DEX groups versus placebo) for all surgical subtypes. Anesthesiologists indicated significantly increased ease of achieving and maintaining targeted sedation in both DEX groups compared with placebo with midazolam (P < 0.001). Patient satisfaction was significantly higher with DEX (P < or = 0.009, both groups versus placebo). Common adverse events with DEX were protocol-defined bradycardia and hypotension that were predominately mild to moderate in severity. The incidence of clinically significant respiratory depression (defined as a respiratory rate of < 8 or an oxygen saturation of < 90%) was lower in DEX-treated patients (P = 0.018, for both groups versus placebo). CONCLUSIONS: DEX is an effective baseline sedative for patients undergoing MAC for a broad range of surgical procedures providing better patient satisfaction, less opioid requirements, and less respiratory depression than placebo rescued with midazolam and fentanyl
— id: 106606, year: 2010, vol: 110, page: 47, stat: Journal Article,

Nimodipine-induced hypotension but not nitroglycerin-induced hypotension preserves long-term memory
Haile M.; Galoyan S.; Li Y.-S.; Quartermain D.; Bekker A.; D'Urso J.
2010 ;22(4):433-433, Journal of neurosurgical anesthesiology
Introduction: Acute hypotension may be implicated in cognitivedysfunction. L-Type calcium channel blockers in the setting of hypoxiaand ischemia are protective of learning and memory. We tested thehypothesis that hypotension induced by nimodipine (NIMO) andnicardipine (NICA) would be protective of long-term associativememory compared with hypotension induced by nitroglycerin (NTG). Methods: After IACUC permission, 30 Swiss-Webster mice (3035 g,68 wk) were randomized into 3 groups for intraperitoneal (IP) injectionimmediately after passive avoidance (PA) learning: (1) NTG (30 mg/kg);(2) NICA (40 mg/kg); and (3) NIMO (40 mg/kg). PA training latencieswere recorded for entry from a suspended platform into a plexiglas tubewhere a shock (0.3 mA; 2 s duration) was automatically delivered. Fortyeighthours later, the latencies were recorded during a testing trial duringwhich no shock was delivered. Latencies greater than 900 s were assignedthis value. Lower testing latency is indicative of an impairment of longtermassociative memory. Mean arterial pressure (MAP) studies inseparate groups of mice determined the dosage for each treatmentrequired to elicit similar degrees of hypotension. Results: Based on the SPSS box plots and the Dixon Gap Test, 1 outliereach from groups 1 and 2 was excluded from the analysis. All groupsexhibited similar training latencies (18 s 6 SIQR). Testing latencies forthe groups were (1) NTG 219.0 s 72.0 SIQR; (2) NICA 360.0 s 68.0SIQR; (3) NIMO 388.5 s 195.0 SIQR. A 2-sided significance ofP=0.025 was found between the testing latencies for NTG and NIMOgroups. Within 10 to 15 minutes of injection, all subjects becameminimally responsive to external stimuli and began to awaken after 5 to6 hours. In a separate group of mice the intergroup difference for MAPwas statistically insignificant.Treatment Baseline MAP (mm Hg) SEM 5 hours Avg% BaselineMAP SEMNTG 30 mg/kg (n=3) 80.9 4.2 54.3 5.1NICAR 40 mg/kg (n=3) 86.7 2.4 49.9 1.4VNIMO 40 mg/kg (n=3) 84 0.3 50.0 1.3Conclusions: Acute hypotension induced by NTG after learning in a PAparadigm causes a dysfunction of long-term associative memory.However, an equivalent decrease in MAP caused by NIMO afterlearning results in loss of memory to a significantly lesser degree. NICAinducedhypotension holds an intermediate position between NTG andNIMO. During periods of neuronal stress caused by low blood flow andreperfusion, L-Type calcium channels are the principal source forcalcium leak and subsequent damage. This study points to a need toinvestigate a potential protective role for L-Type calcium channel blockers in procedures where hypotension is induced, particularly inpatients whose cerebrovascular disease brings the safety of acceptedlevels of MAP into question. Summary: NIMO induced hypotension but neither NTG nor NICAinducedhypotension preserves long-term associative memory in mice
— id: 114213, year: 2010, vol: 22, page: 433, stat: Journal Article,

A prospective, randomized, placebo-controlled study evaluating the efficacy of dexmedetomidine for sedation during vascular procedures
Huncke, Tessa Kate; Adelman, Mark; Jacobowitz, Glenn; Maldonado, Thomas; Bekker, Alex
2010 May;44(4):257-261, Vascular & endovascular surgery
OBJECTIVE: To examine the efficacy of dexmedetomidine (DEX) as a primary sedative during vascular procedures performed under monitored anesthesia care (MAC). A total of 55 patients were randomized in a 2:2:1 ratio to receive either DEX 1.0 microg/kg load or DEX 0.5 microg/kg load versus midazolam (MDZ) boluses, the current standard of care. This was followed by a maintenance infusion of DEX versus a normal saline infusion for the control group. Midazolam was given in 0.5 mg increments to maintain an equivalent target level of sedation among the 3 study groups. Fentanyl was given in 25 microg increments to treat pain as needed. The percentage of DEX patients not requiring MDZ and the total dose of MDZ and fentanyl were compared to the control. Dexmedetomidine was efficacious as a sole sedative for 50% of patients. The total dose of MDZ and fentanyl was significantly less during the DEX infusions. Patient satisfaction was superior with DEX
— id: 109213, year: 2010, vol: 44, page: 257, stat: Journal Article,

Nimodipine prevents memory impairment caused by nitroglycerin-induced hypotension in adult mice
Bekker, Alex; Haile, Michael; Li, Yong-Sheng; Galoyan, Samuel; Garcia, Edwardo; Quartermain, David; Kamer, Angela; Blanck, Thomas
2009 Dec;109(6):1943-1948, Anesthesia & analgesia
BACKGROUND: Hypotension and a resultant decrease in cerebral blood flow have been implicated in the development of cognitive dysfunction. We tested the hypothesis that nimodipine (NIMO) administered at the onset of nitroglycerin (NTG)-induced hypotension would preserve long-term associative memory. METHODS: The passive avoidance (PA) paradigm was used to assess memory retention. For PA training, latencies (seconds) were recorded for entry from a suspended platform into a Plexiglas tube where a shock was automatically delivered. Latencies were recorded 48 h later for a testing trial. Ninety-six Swiss-Webster mice (30-35 g, 6-8 wk), were randomized into 6 groups 1) saline (control), 2) NTG immediately after learning, 3) NTG 3 h after learning, 4) NTG and NIMO, 5) vehicle, and 6) NIMO alone. The extent of hypotension and changes in brain tissue oxygenation (PbtO(2)) and in cerebral blood flow were studied in a separate group of animals. RESULTS: All groups exhibited similar training latencies (17.0 +/- 4.6 s). Mice subjected to hypotensive episodes showed a significant decrease in latency time (178 +/- 156 s) compared with those injected with saline, NTG + NIMO, or delayed NTG (580 +/- 81 s, 557 +/- 67 s, and 493 +/- 146 s, respectively). A Kruskal-Wallis 1-way analysis of variance indicated a significant difference among the 4 treatment groups (H = 15.34; P < 0.001). In a separate group of mice not subjected to behavioral studies, the same dose of NTG (n = 3) and NTG + NIMO (n = 3) caused mean arterial blood pressure to decrease from 85.9 +/- 3.8 mm Hg sem to 31.6 +/- 0.8 mm Hg sem and from 86.2 +/- 3.7 mm Hg sem to 32.6 +/- 0.2 mm Hg sem, respectively. Mean arterial blood pressure in mice treated with NIMO alone decreased from 88.1 +/- 3.8 mm Hg to 80.0 +/- 2.9 mm Hg. The intergroup difference was statistically significant (P < 0.05). PbtO(2) decreased from 51.7 +/- 4.5 mm Hg sem to 33.8 +/- 5.2 mm Hg sem in the NTG group and from 38.6 +/- 6.1 mm Hg sem to 25.4 +/- 2.0 mm Hg sem in the NTG + NIMO groups, respectively. There were no significant differences among groups. CONCLUSION: In a PA retention paradigm, the injection of NTG immediately after learning produced a significant impairment of long-term associative memory in mice, whereas delayed induced hypotension had no effect. NIMO attenuated the disruption in consolidation of long-term memory caused by NTG but did not improve latency in the absence of hypotension. The observed effect of NIMO may have been attributable to the preservation of calcium homeostasis during hypotension, because there were no differences in the PbtO(2) indices among groups
— id: 105366, year: 2009, vol: 109, page: 1943, stat: Journal Article,

Nimodipine prevents transient cognitive dysfunction after moderate hypoxia in adult mice
Haile, Michael; Limson, Fred; Gingrich, Kevin; Li, Yong-Sheng; Quartermain, David; Blanck, Thomas; Bekker, Alex
2009 Apr;21(2):140-144, Journal of neurosurgical anesthesiology
BACKGROUND: Cognitive changes associated with moderate hypoxia may be related to the elevation of cytosolic calcium (Ca) levels which may, in turn, affect neurotransmitter synthesis and metabolism. We tested whether treatment with nimodipine (NIMO), an L-type Ca channel blocker, would preserve working memory after hypoxic hypoxia. METHODS: We randomized 157 Swiss-Webster, 30 to 35 g mice (6 to 8 wk) to 6 groups, which were exposed to the following gas mixtures for 1 hour: (1) O2 21%; (2) O2 21% followed by 0.1 mg/kg of subcutaneous NIMO; (3) O2 21% followed by vehicle (60% polyethylene glycol/40% methanol); (4) O2 10%; (5) O2 10% then NIMO; (6) O2 10% then vehicle. The Object Recognition Test (ORT) was given once either on Day 1 or Day 7 to assess changes in short-term memory. ORT exploits the tendency of mice to prefer novel over familiar objects. Two identical objects were placed in an arena for 15 minutes of training. During the testing 1 hour later, one of the objects was replaced by a new object. Recognition Index (RI) was used to compare performance. It is defined as the time spent exploring the novel object divided by the time spent exploring both objects, the novel plus the familiar, and this ratio is converted to a percentage. RI was analyzed with analysis of variance. Tukey Honestly Significant Difference tests were used for post hoc comparisons when appropriate. P values <0.05 were considered significant. RESULTS: RI for the control group was 68.3% (SE+/-3.6%). RI was 53.7% (SE+/-3.8%) for the 10% O2 group on the first posttreatment day. O2 saturation (SpO2) for the hypoxic group was 71.7% (SE+/-0.5%). By Day 7, RI for the 10% O2 group increased to 64.2% (SE+/-4.7%), which was not significantly different from control. On Day 1, RI was 68.6% (SE+/-5.2%) for hypoxic rodents treated with NIMO. These results were statistically significant. Low RI indicates impaired working memory and high RI indicates intact working memory. These results suggest that NIMO prevented impairment of working memory after moderate hypoxia. CONCLUSIONS: NIMO reverses the disturbance of short-term working memory caused by moderate hypoxia in mice. The results may have implications for cognitive changes linked to Ca homeostasis in the postoperative period
— id: 132606, year: 2009, vol: 21, page: 140, stat: Journal Article,

The effect of dexmedetomidine on perioperative hemodynamics in patients undergoing craniotomy
Bekker, Alex; Sturaitis, Mary; Bloom, Marc; Moric, Mario; Golfinos, John; Parker, Erik; Babu, Ramesh; Pitti, Abishabeck
2008 Oct;107(4):1340-1347, Anesthesia & analgesia
BACKGROUND: The perioperative course of patients undergoing intracranial surgery is frequently complicated by hypertensive episodes. Dexmedetomidine (DEX), an alpha-2 adrenoreceptor agonist, is gaining popularity in neuroanesthesia, because its sympatholytic and antinociceptive properties may improve hemodynamic stability at critical moments of surgery. We designed this study to assess the efficacy of DEX in controlling hypertensive responses in patients undergoing intracranial surgery. METHODS: Patients scheduled for elective craniotomy were randomly assigned to receive either sevoflurane-opioid or sevoflurane-opioid-DEX anesthesia. Bispectral index was used to maintain a similar level of hypnosis in both groups (40-50). Opioids, sevoflurane, and vasoactive medications were titrated in a routine manner, at the discretion of the blinded anesthesiologist managing the case, to maintain systolic blood pressure (SBP) targeted within 90-130 mm Hg and heart rate (HR) between 50 and 90 bpm. Hemodynamic variables were continuously recorded and stored on a computer for analysis. Efficacy of the anesthetic technique in controlling SBP or HR is inversely proportional to the area under the curve (AUC) outside the targeted range. Areas under the curves above and below targeted ranges for SBP-time (AUCsbp mm Hg*min/h) and HR-time (bpm*min/h) were compared. Coefficient of variation was used to assess hemodynamic stability. RESULTS: Seventy-two patients were recruited for the study. Computerized records of 56 patients only were analyzed because of technical problems with data collection in 14 cases. AUCsbp for above the targeted range was significantly lower for patients in the DEX group (P=0.044). The coefficient of variation for SBP or HR did not differ between groups. A significantly smaller proportion of patients in the DEX group required treatment with antihypertensive medications (12 of 28, 42% vs 24 of 28, 86%, P=0.0008). The DEX group required fewer opioids in the intraoperative period, but there were no differences in the use of sevoflurane. In the postanesthesia care unit, patients in the DEX group had fewer hypertensive episodes (1.25+/-1.55 vs 2.50+/-2.00, P=0.0114) and were discharged earlier (91+/-17 vs 130+/-27 min, P<0.0001). There were no differences in the requirement for postoperative opioids or antiemetics. CONCLUSIONS: By using indices, which assess a global hemodynamic stability of the anesthetic, we determined that intraoperative DEX infusion was effective for blunting the increases in SBP perioperatively. The use of DEX did not increase the incidence of hypotension or bradycardia, common side effects of the drug
— id: 87811, year: 2008, vol: 107, page: 1340, stat: Journal Article,

The use of continuous positive airway pressure during an awake craniotomy in a patient with obstructive sleep apnea
Huncke, Tessa; Chan, Jenny; Doyle, Werner; Kim, Jung; Bekker, Alex
2008 Jun;20(4):297-299, Journal of clinical anesthesia
We describe the anesthetic management of a morbidly obese patient with obstructive sleep apnea who underwent awake craniotomy. The patient's personal continuous positive airway pressure (CPAP) machine was used to support ventilation intraoperatively. Dexmedetomidine was used as the primary sedative. During cortical mapping, the CPAP was discontinued. The patient was comfortable and able to cooperate with language testing
— id: 93336, year: 2008, vol: 20, page: 297, stat: Journal Article,

Physostigmine reverses cognitive dysfunction caused by moderate hypoxia in adult mice
Bekker, Alex; Haile, Michael; Gingrich, Kevin; Wenning, Leslie; Gorny, Alex; Quartermain, David; Blanck, Thomas
2007 Sep;105(3):739-743, Anesthesia & analgesia
BACKGROUND: Cognitive changes associated with moderate hypoxia in rodents may result from the diminished functioning of central cholinergic neurotransmission. We designed this study to examine whether treatment with physostigmine (PHY), an acetylcholinesterase inhibitor, could improve the impairment of working memory after hypoxic hypoxia. METHODS: We randomized 90 Swiss Webster, 30-35 g mice (6-8 wks) to three hypoxia groups at fraction of inspired oxygen, FiO2 = 0.10 (1. no treatment; 2. PHY 0.1 mg/kg intraperitoneally administered immediately before; or 3. after hypoxia), or to two room air groups (given either no treatment or PHY after an insult). An object recognition test was used to assess short-term memory function. The object recognition test exploits the tendency of mice to prefer exploring novel objects in an environment when a familiar object is also present. During the 15 min training trial, two identical objects were placed in two defined sites of the box. During the test trial performed 1 h later, one of the objects was replaced by a new object with a different shape. The time spent exploring the two objects was automatically recorded by a video camera and associated software. The performance was analyzed with ANOVA, followed by post hoc comparisons using the Newman-Keuls test when appropriate. P values <0.05 were considered significant. RESULTS: Untreated mice subjected to hypoxia at Fio2 = 0.1 spent significantly less time exploring a novel object on testing day 1 than did untreated mice breathing room air. Performance of the mice subjected to hypoxia, who received physostigmine after, but not before, the insult did not differ from the control group. CONCLUSION: Moderate hypoxia impairs rodents' performance in a working memory task. It appears that changes are transient, because the cognitive functioning of the mice returned to the baseline level 7 days after treatment. Postinsult administration of PHY prevented deterioration of cognitive function. An increased level of acetylcholine in the central nervous system may be responsible for the improved performance of the hypoxia-treated mice
— id: 86616, year: 2007, vol: 105, page: 739, stat: Journal Article,

Treatment with lavender aromatherapy in the post-anesthesia care unit reduces opioid requirements of morbidly obese patients undergoing laparoscopic adjustable gastric banding
Kim, Jung T; Ren, Christine J; Fielding, George A; Pitti, Abhishek; Kasumi, Takeo; Wajda, Michael; Lebovits, Allen; Bekker, Alex
2007 Jul;17(7):920-925, Obesity surgery
BACKGROUND: Parenteral administration of opioids and NSAIDs has been the mainstay for postoperative pain control in patients undergoing laparoscopic adjustable gastric banding (LAGB). Both classes of drugs, however, are associated with serious adverse effects. An addition of complimentary analgesic techniques may decrease requirement for traditional analgesics, thus reducing the incidence of side-effects. We designed the study to evaluate the effectiveness of Lavender aromatherapy in reducing opioid requirements after LAGB. METHODS: A prospective randomized placebo controlled study was carried out on 54 patients undergoing LAGB. Upon arrival to the post-anesthesia care unit (PACU), patients in the study group were treated with lavender oil, which was applied to the oxygen face mask; the control group patients received nonscented baby oil. Postoperative pain was treated with morphine. Numerical rating scores (0-10) were used to measure the level of pain at 5, 30, and 60 min. Sedation was evaluated using the Observer Assessment of Alertness/Sedation scale (0-5). Data analyzed included the amount of opioids, NRS, OAA/S, PACU discharge time, as well as the incidence of side-effects. RESULTS: The two groups were comparable with regard to patient characteristics, intraoperative drug use, and surgical time. Significantly more patients in the Placebo group (PL) required analgesics for postoperative pain (22/27, 82%) than patients in the Lavender group (LAV) (12/26, 46%) (P = .007). Moreover, the LAV patients required significantly less morphine postoperatively than PL patients: 2.38 mg vs 4.26 mg, respectively (P = .04). There were no differences in the requirements for post-operative antiemetics, antihypertensives, or PACU discharge time. CONCLUSIONS: Our results suggest that lavender aromatherapy can be used to reduce the demand for opioids in the immediate postoperative period. Further studies are required to assess the effect of this therapy on clinically meaningful outcomes, such as the incidence of respiratory complications, delayed gastric emptying, length of hospital stay, or whether this therapy is applicable to other operations
— id: 74527, year: 2007, vol: 17, page: 920, stat: Journal Article,

Dexmedetomidine does not increase the incidence of intracarotid shunting in patients undergoing awake carotid endarterectomy
Bekker, Alex; Gold, Mark; Ahmed, Raza; Kim, Jung; Rockman, Caron; Jacobovitz, Glenn; Riles, Thomas; Fisch, Gene
2006 Oct;103(4):955-958, Anesthesia & analgesia
Systemic administration of dexmedetomidine (DEX) decreases cerebral bloodflow (CBF) via direct alpha-2-mediated constriction of cerebral blood vessels and indirectly via its effect on the intrinsic neural pathway modulating vascular smooth muscle. Reduction in CBF without a concomitant decrease in cerebral metabolic rate has raised concerns that DEX may limit adequate cerebral oxygenation of brain tissue in patients with already compromised cerebral circulation (e.g., carotid endarterectomy [CEA]). In this study, we established the incidence of intraarterial shunting used as a sign of inadequate oxygen delivery in a consecutive series of 123 awake CEA performed in our institution using DEX as a primary sedative. Data were prospectively recorded in 151 patients who underwent CEA during the study period. Eighteen patients were sedated with midazolam and fentanyl (M/F) for medical or logistical reasons. Patients thought to be at risk of an intraoperative stroke were treated with a prophylactic intraarterial shunt. These patients, as well as those who required general anesthesia, were excluded from the final analysis. Five patients (4.3%) in the DEX group required intraarterial shunts. The incidence of shunting in patient undergoing awake CEA in our institution is 10% (historical control). No patients developed a stroke or other serious complications. It appears that the use of DEX as a primary sedative drug for CEA does not increase the incidence of intraarterial shunts
— id: 68990, year: 2006, vol: 103, page: 955, stat: Journal Article,

Isoflurane preserves spatial working memory in adult mice after moderate hypoxia
Bekker, Alex; Shah, Romin; Quartermain, David; Li, Yong-Sheng; Blanck, Thomas
2006 Apr;102(4):1134-1138, Anesthesia & analgesia
Perioperative hypoxia may contribute to postoperative cognitive impairment. It is unknown, however, whether anesthetics exacerbate or protect against hypoxia-related central nervous system impairment. We sought to determine whether hypoxia alone or in combination with isoflurane disrupts working memory in mice. To this extent, we assigned adult mice to one of four treatments for 1 h: oxygen 21%, oxygen 21% + isoflurane 1.2%, oxygen 8%, or oxygen 8% + isoflurane 1.2%. Mice breathed spontaneously throughout the experiment. Body temperature was maintained at 37 degrees C + 0.5 degrees C. Mice were allowed to recover for 24 h to avoid the confounding influence of residual anesthetics on neurobehavioral performance. Working memory was assessed by use of a Y maze modified for mice. For the training trial, entry to one arm was blocked and mice were permitted to run between the two open arms for 15 min and inspect the objects outside. For the test trial, carried out 1 h later, all arms were open. Time spent in each arm was automatically recorded by a camera and associated software. Mice were tested 1, 4, and 7 days after anesthesia. A different arm was used as the novel arm for each test. Performance was analyzed with repeated-measurements analysis of variance, followed by analysis of simple main effects and by post hoc comparison using Newman-Keuls test when appropriate. P values <0.05 were considered significant. Animals subjected to hypoxia (8% oxygen for 1 h) spent significantly less time in the novel arm 1 day after the insult. The impairment, however, was transient. Hypoxic mice performance improved to the level of the control animals on the fourth post-treatment day. Mice subjected to hypoxia plus isoflurane exhibited no impairment and were comparable to the control group at all time points. Hypoxia transiently impairs performance in a spatial memory task. It appears that isoflurane protects against this deleterious effect of hypoxia
— id: 63746, year: 2006, vol: 102, page: 1134, stat: Journal Article,

Evaluation of aromatherapy in treating postoperative pain: pilot study
Kim, Jung T; Wajda, Michael; Cuff, Germaine; Serota, David; Schlame, Michael; Axelrod, Deborah M; Guth, Amber A; Bekker, Alex Y
2006 Dec;6(4):273-277, Pain practice
This study compared the analgesic efficacy of postoperative lavender oil aromatherapy in 50 patients undergoing breast biopsy surgery. Twenty-five patients received supplemental oxygen through a face mask with two drops of 2% lavender oil postoperatively. The remainder of the patients received supplemental oxygen through a face mask with no lavender oil. Outcome variables included pain scores (a numeric rating scale from 0 to 10) at 5, 30, and 60 minutes postoperatively, narcotic requirements in the postanesthesia care unit (PACU), patient satisfaction with pain control, as well as time to discharge from the PACU. There were no significant differences in narcotic requirements and recovery room discharge times between the two groups. Postoperative lavender oil aromatherapy did not significantly affect pain scores. However, patients in the lavender group reported a higher satisfaction rate with pain control than patients in the control group (P = 0.0001)
— id: 69409, year: 2006, vol: 6, page: 273, stat: Journal Article,

Ultrasound-guided lumbar plexus block for open reduction and internal fixation of hip fracture
Morimoto, Maki; Kim, Jung T; Popovic, Jovan; Jain, Sudheer; Bekker, Alex
2006 Jun;6(2):124-126, Pain practice
PURPOSE: Ultrasound technology has been applied to increase both efficacy and safety of certain peripheral nerve blocks. This case report describes the first successful ultrasound-guided lumber plexus block. CLINICAL FEATURES: We describe a 91-year-old woman with aortic stenosis who successfully underwent open reduction and internal fixation of a fractured right hip with a lumbar plexus block. Ultrasound provided direct visualization to help identify the anatomical structures and guide the block needle during performance of the block. Complete block of the lumbar plexus was attained within 15 min, and the surgical procedure was performed uneventfully. CONCLUSION: The use of ultrasound has gained popularity to perform peripheral nerve blocks. In this case report, a successful lumbar plexus block was performed with ultrasound guidance. By direct visualization, using this technology may potentially reduce complications associated with lumbar plexus blocks
— id: 71212, year: 2006, vol: 6, page: 124, stat: Journal Article,

Dexmedetomidine in awake craniotomy: a technical note
Ard, John L Jr; Bekker, Alex Y; Doyle, Werner K
2005 Feb;63(2):114-116, Surgical neurology
BACKGROUND: Resection of lesions in eloquent areas of the brain are sometimes best done with the patient awake. An awake patient provides neurological feedback as the lesion is resected. This increases the chances of a complete resection without leaving a patient neurologically devastated. Unfortunately, this procedure is not always well tolerated by the patient. METHODS: We performed a case series of awake craniotomies using a dexmedetomidine infusion. RESULTS: All 17 patients included in our study tolerated the procedure well with no major complications. CONCLUSIONS: The addition of dexmedetomidine to our technique improves safety and comfort for patients undergoing awake craniotomy
— id: 49009, year: 2005, vol: 63, page: 114, stat: Journal Article,

Anesthesia for an adult with mucopolysaccharidosis I
Ard, John L Jr; Bekker, Alex; Frempong-Boadu, Anthony K
2005 Dec;17(8):624-626, Journal of clinical anesthesia
We describe the anesthetic management difficulties of a man with mucopolysaccharidosis I. We also briefly review the anesthesia literature related to this disease
— id: 63835, year: 2005, vol: 17, page: 624, stat: Journal Article,

Dexmedetomidine for neurological surgery
Bekker, Alex; Sturaitis, Mary K
2005 Jul;57(1 Suppl):1-10, Neurosurgery
Dexmedetomidine is a new intravenous drug gaining popularity in neuroanesthesia and neurocritical care practice. This alpha2-adrenergic receptor agonist offers a unique 'cooperative sedation,' anxiolysis, and analgesia with no respiratory depression. Cerebral effects are generally consistent with a desirable neurophysiological profile, including neuroprotective characteristics. In addition, sympatholytic and antinociceptive properties allow for hemodynamic stability at critical moments of neurosurgical stimulation. This review will address the neuropharmacology and neurophysiology of alpha2-adrenergic agonists and will specifically consider the rapidly evolving applicability of dexmedetomidine as an adjuvant to neurosurgical case management
— id: 58975, year: 2005, vol: 57, page: 1, stat: Journal Article,

A double-blind prospective comparison of rofecoxib vs ketorolac in reducing postoperative pain after arthroscopic knee surgery
Kim, Jung T; Sherman, Orrin; Cuff, Germaine; Leibovits, Allen; Wajda, Michael; Bekker, Alex Y
2005 Sep;17(6):439-443, Journal of clinical anesthesia
STUDY OBJECTIVE: The aim of this study was to compare the analgesic efficacy of premedication with rofecoxib vs intravenous (IV) ketorolac in reducing postoperative pain after arthroscopic knee surgery. STUDY DESIGN: This is a prospective, randomized, double-blinded study. SETTING: This study was set at a university hospital. SUBJECTS: The subjects include 54 patients with American Society of Anesthesiologists physical statuses I, II, and III undergoing knee arthroscopy. INTERVENTIONS: Group 1 received 50 mg oral rofecoxib preoperatively with IV placebo injection, which was administered 20 minutes before the end of the operation. Group 2 received a preoperative placebo and 30 mg IV ketorolac 20 minutes before the end of surgery. MEASUREMENTS: The primary outcome measure was the proportion of patients reporting pain in the postoperative anesthesia care unit, 6 hours and 24 hours after discharge. Additional end points included the use of 5:325 mg oxycodone-acetaminophen (O/A) tablets, pain scores, patient's satisfaction survey, and comparison of side effects. Data were analyzed using independent samples t tests for continuous variables or chi2 tests for categorical variables. P < .05 was considered significant. RESULTS: The 2 groups were comparable with regard to patient characteristics, intraoperative medication use, and duration of surgery. There was no difference either in pain scores or O/A use in the postoperative anesthesia care unit. At 24 hours after discharge, significantly more patients in the ketorolac group (91%) reported pain than the rofecoxib group (63%) (P = .02). Sixty-one percent of patients in the ketorolac group used O/A during the first 24 hours vs 38% in the rofecoxib group. The difference, however, was not statistically significant. CONCLUSION: Preoperative rofecoxib is as effective as ketorolac for the treatment of pain after knee arthroscopy. Higher frequency of pain reporting at 24 hours by patients in ketorolac group is explained by the longer analgesic effect of rofecoxib. Future studies should directly compare gastrointestinal injury of these drugs, as well as cost-effectiveness of rofecoxib vs ketorolac
— id: 58974, year: 2005, vol: 17, page: 439, stat: Journal Article,

Alpha-2 agonists in neuroanesthesia
Bekker A; Jorden VSB
2004 ;23(3):181-191, Seminars in anesthesia
— id: 46296, year: 2004, vol: 23, page: 181, stat: Journal Article,

Dexmedetomidine as primary sedative in CEA patients - In reply
Bekker, A; Gold, M
2004 OCT ;16(4):320-321, Journal of neurosurgical anesthesiology
— id: 46484, year: 2004, vol: 16, page: 320, stat: Journal Article,

Dexmedetomidine for awake carotid endarterectomy: efficacy, hemodynamic profile, and side effects
Bekker, Alex Y; Basile, John; Gold, Mark; Riles, Thomas; Adelman, Mark; Cuff, Germaine; Mathew, Jomol P; Goldberg, Judith D
2004 Apr;16(2):126-135, Journal of neurosurgical anesthesiology
: A randomized, double-masked, placebo-controlled study was designed to compare dexmedetomidine as a primary sedative agent with a commonly used drug combination in patients undergoing awake carotid endarterectomy (CEA). Sixty-six patients undergoing CEA (ASA II-IV) were randomly assigned to receive either dexmedetomidine (total dose of 97.5 +/- 54.7 mcg) or normal saline (control). Supplemental doses of midazolam, fentanyl, and/or propofol were administered as deemed necessary by the anesthesiologist. An observer blinded to the study drug assessed sedation level (Observer's Assessment of Alertness-Sedation [OAA/S] scale). The primary outcomes were defined as the number of patients with an OAA/S score of 4 intraoperatively and an OAA/S score of 5 postoperatively. The authors also compared cardiorespiratory parameters, intra- and postoperative side effects, and complications. Chi-square tests were used to analyze the primary endpoints. All secondary parameters were analyzed using the Wilcoxon rank sum test. Three patients in the dexmedetomidine group (10%) had an OAA/S score of 4 at all four time points assessed intraoperatively, while no patient in the control group had a score of 4 at all the time points considered. Thirteen patients in the dexmedetomidine group had a score of 4 at three or more time points (42%) compared with six patients (19%) in the control group. Four patients in the control group (13%) and one patient in the dexmedetomidine group (3%) did not achieve a score of 4 at any of the four critical intraoperative time points (chi for association = 9.9, P < 0.05; chi for a trend = 8.6, P < 0.004, with the trend favoring dexmedetomidine). More patients in the control group required treatment with metoprolol (26% vs. 6%, P = 0.04) and labetalol (48% vs/ 6%, P < 0.01). Plasma levels of norepinephrine were significantly lower in the dexmedetomidine group during and after surgery compared with the control group. Six patients (19%) in the dexmedetomidine group required intra-arterial shunts, while only two patients (6%) required shunts in the control group (P = 0.16). These data show that the use of dexmedetomidine in patients undergoing awake CEA resulted in fewer fluctuations from the desired sedation level. Patients receiving dexmedetomidine required less antihypertensive therapy compared with the midazolam/fentanyl/propofol combination. The effect of dexmedetomidine on cerebrovascular circulation in the study population needs further investigation
— id: 43212, year: 2004, vol: 16, page: 126, stat: Journal Article,

Awake craniotomy with dexmedetomidine in pediatric patients
Ard, John; Doyle, Werner; Bekker, Alex
2003 Jul;15(3):263-266, Journal of neurosurgical anesthesiology
We present our experience with the use of dexmedetomidine, an alpha2 agonist, in two children undergoing awake craniotomy. General anesthesia with the laryngeal mask airway was used for parts of the procedure not requiring patient cooperation to reduce the duration of wakefulness and abolish the discomfort of surgical stimulation. Dexmedetomidine was used as a primary anesthetic for brain mapping of the cortical speech area. The asleep-awake-sleep technique provided adequate sedation and analgesia throughout the surgery and allowed the patient to complete the necessary neuropsychological tests. To our knowledge, ours is the first description of the use of dexmedetomidine in pediatric neurosurgery
— id: 42665, year: 2003, vol: 15, page: 263, stat: Journal Article,

Cognitive function after anaesthesia in the elderly
Bekker, Alex Y; Weeks, Edwin J
2003 Jun;17(2):259-272, Best practice & research. Clinical anaesthesiology
Despite advances in peri operative care, a significant percentage of elderly patients experience transient post operative delirium and/or long-term post-operative cognitive dysfunction (POCD). This chapter reviews the aetiology, clinical features, preventive strategies and treatment of these syndromes. Pre-operative, intra-operative, and post-operative risk factors for delirium and POCD following cardiac and non-cardiac surgery are discussed. It is most likely that the aetiology of delirium and POCD is multifactorial and may include factors such as age, decreased pre-operative cognitive function, general health status and, possibly, intra-operative events. Currently there is no single therapy that can be recommended for treating post-operative cognitive deterioration. Primary prevention of delirium and POCD is probably the most effective treatment strategy. Several large clinical trials show the effectiveness of multicomponent intervention protocols that are designed to target well-documented risk factors in order to reduce the incidence of post-operative delirium and, possibly, POCD in the elderly
— id: 58976, year: 2003, vol: 17, page: 259, stat: Journal Article,

Preoperative rofecoxib administration reduces postoperatie pioid requirements after lumbar disc surgery: a double-blinded placebo=controlled evaluation
Bekker A; Pryadko A; Cooper P; Sorour K; Smawley K; Lebovits A
2002 ;94:S232-S232, Anesthesia & analgesia
— id: 47216, year: 2002, vol: 94, page: S232, stat: Journal Article,

Evaluation of preoperative administration of the cyclooxygenase-2 inhibitor rofecoxib for the treatment of postoperative pain after lumbar disc surgery
Bekker, Alex; Cooper, Paul R; Frempong-Boadu, Anthony; Babu, Ramesh; Errico, Thomas; Lebovits, Allen
2002 May;50(5):1053-1057, Neurosurgery
OBJECTIVE: A combination of analgesics with different mechanisms of action may improve postoperative pain control and reduce the incidence of side effects. This study was designed to assess the efficacy of preoperative administration of rofecoxib (Vioxx; Merck & Co., Inc., Somerset, NJ) in reducing pain and opioid requirements after single-level lumbar microdiscectomy. METHODS: A randomized, double-blind, placebo-controlled clinical trial was performed on 61 consenting patients who were considered American Society of Anesthesiologists Class I or II and who were scheduled for elective single-level lumbar microdiscectomy. Patients received either two doses of rofecoxib 50 mg or a placebo preoperatively. The outcome measures included morphine use in the postanesthesia care unit (PACU), discharge times, and side effect profile. Data were analyzed by use of independent sample t tests for continuous variables or chi(2) tests for categorical variables. A P value of <0.05 was considered significant. RESULTS: The two groups were comparable with respect to patient characteristics, intraoperative opioid and hypnotic consumption, and duration of surgery. Patients in the rofecoxib group required significantly less morphine postoperatively. Significantly more patients in the placebo group reported pain scores greater than 7 at admission to the PACU. Time to first request for analgesia was shorter in the placebo group, but the difference did not reach statistical significance. There were no significant differences between groups in the incidence of nausea, time to discharge from the PACU, or hospital stay. CONCLUSION: Preoperative rofecoxib is effective in reducing postoperative narcotic consumption in patients undergoing lumbar laminectomy. The use of rofecoxib does not shorten PACU length of stay or hospital discharge time. These outcome measures depend on multiple administrative factors
— id: 48718, year: 2002, vol: 50, page: 1053, stat: Journal Article,

The use of cardioselective beta-blockers in a patient with idiopathic hypertrophic subaortic stenosis and chronic obstructive pulmonary disease
Bekker, Alex; Sorour, Khaled; Miller, Sanford
2002 Dec;14(8):589-591, Journal of clinical anesthesia
The beta-adrenergic receptor blocking drugs are commonly used in the treatment of patients with idiopathic hypertropic subaortic stenosis (IHSS). These drugs, however, are contraindicated in patients with chronic obstructive pulmonary disease (COPD). We report the anesthetic management of a patient with IHSS complicated by severe COPD. We concluded that the beta(1) selective, ultra-short acting beta-blocker, esmolol, can be used intraoperatively when both conditions are present. The pathophysiology and the commonly used anesthetic drugs and practices for treatment of patients with IHSS are reviewed
— id: 58977, year: 2002, vol: 14, page: 589, stat: Journal Article,

The use of dexmedetomidine infusion for awake craniotomy
Bekker AY; Kaufman B; Samir H; Doyle W
2001 May;92(5):1251-1253, Anesthesia & analgesia
— id: 20704, year: 2001, vol: 92, page: 1251, stat: Journal Article,

Dexmedetomidine infusion and somatosensory evoked potentials
Bloom M; Beric A; Bekker A
2001 Oct;13(4):320-322, Journal of neurosurgical anesthesiology
Intraoperative neurophysiologic monitoring requires information on the effects of anesthetic drugs because these drugs can directly alter evoked potentials, thus interfering with monitoring. We report on our evaluation of the effect of the recently introduced alpha2-adrenergic agonist, dexmedetomidine, on the somatosensory evoked potentials in two patients undergoing cervico-occipital fusion. Our results suggest that, although dexmedetomidine can affect the later cortical peaks of somatosensory evoked potentials (SSEPs), consistent and reproducible potentials can be recorded
— id: 26547, year: 2001, vol: 13, page: 320, stat: Journal Article,

Dilation of cerebral collateral circulation may improve perfusion to ischemic area distal to vasospasm
Bekker A; Mass HJ; Ursino M
2000 ;12:403-403, Journal of neurosurgical anesthesiology
— id: 47265, year: 2000, vol: 12, page: 403, stat: Journal Article,

The recovery of cognitive function after remifentanil-nitrous oxide anesthesia is faster than after an isoflurane-nitrous oxide-fentanyl combination in elderly patients
Bekker AY; Berklayd P; Osborn I; Bloom M; Yarmush J; Turndorf H
2000 Jul;91(1):117-122, Anesthesia & analgesia
We tested the hypothesis that remifentanil-nitrous oxide (N(2)O) anesthesia shortens postoperative emergence and recovery compared with an isoflurane-N(2)O-fentanyl combination in elderly patients undergoing spinal surgery. A total of 60 patients (>65 yr old) were randomly assigned to one of two groups for maintenance of anesthesia. After the induction with 3.6 +/- 1.2 mg/kg IV thiopental and endotracheal intubation facilitated with 1.4 +/- 0.5 mg/kg succinylcholine, patients were maintained with either 0.5%-1.5% isoflurane, 70% N(2)O, and up to 7 microg/kg fentanyl (iso/fent group) or 48 +/- 11 microg/kg remifentanil and 70% N(2)O (remi group). A mini-mental status examination was used to assess cognitive ability preoperatively, at 15, 30, and 60 min after arrival at the postanesthesia care unit and again 12-24 h postoperatively. The time from the conclusion of anesthesia to spontaneous respiration was similar in both groups. Times to eye opening (4.8 +/- 2.6 vs 2.3 +/- 1.1 min), extubation (6.8 +/- 3.8 vs 3.2 +/- 2.1 min), and verbalization (9.9 +/- 6.2 vs 3.9 +/- 2.6 min) were significantly shorter for the remi group (P < 0.05). Postoperative mini-mental status examination scores were significantly lower in the iso/fent group at 15 (16.3 +/- 5.8 vs 23. 7 +/- 3.3), 30 (20.2 +/- 5.2 vs 26.3 +/- 2.7), and 60 min (23.5 +/- 4.4 vs 27.5 +/- 2.0) (P < 0.001); however, the scores equalized after 12 h. Requirements for postoperative analgesics were similar in the two groups. More patients in the remi group were treated with antiemetics (21 vs 7, P = 0.06). Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit; a stay is often related to multiple administrative issues, rather than cognitive recovery. IMPLICATIONS: Maintenance of anesthesia with remifentanil-nitrous oxide (N(2)O), compared with isoflurane-N(2)O-fentanyl, can safely shorten postoperative recovery of cognitive function in a geriatric population. Earlier recovery may facilitate postoperative neurological assessment. Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit, a stay often related to multiple administrative issues, rather than cognitive recovery
— id: 11636, year: 2000, vol: 91, page: 117, stat: Journal Article,

Basic principles of total intravenous anesthesia
Bekker AY; O'Neill D; Rambissoon G
2000 ;20:243-249, Current reviews in clinical anesthesia
— id: 45597, year: 2000, vol: 20, page: 243, stat: Journal Article,

Comparison of cardiotropic drug effects on haemodynamic and myocardial energetics in patients with heart failure: a computer simulation
Bekker AY; Wolk S; Rim J; Turndorf H; Ritter AB
2000 May-Jun;24(3):87-94, Journal of medical engineering & technology
The purpose of our study is to compare haemodynamic responses and the ischaemic potential of commonly used inotropes (dopamine, dobutamine and milrinone) using a computer model of the cardiovascular system. Cardiotropic drugs interact with the model by changing ventricular elastance and resistance of the individual circulation. All three drugs increase cardiac index in a dose-dependent manner. Dopamine at medium and high infusion rates increases heart rate, systemic vascular resistance and arterial blood pressure. The associated increase in coronary blood flow, however, is not sufficient to account for increased oxygen demand. Both dobutamine and milrinone decrease vascular resistance and increase coronary blood flow. The more pronounced increase in heart rate associated with dobutamine, however, results in a higher ischaemic potential for this drug. Our simulation demonstrates that although all the drugs studied improve cardiac function in simulated patients with heart failure, milrinone accomplishes this at a lower energy cost. The computer simulation developed can be used to assess the complex effect of cardiotropic drugs and possibly suggest optimal drug therapy in specific clinical situations
— id: 45791, year: 2000, vol: 24, page: 87, stat: Journal Article,

Development and testing of a simulated closed loop drug delivery system for congestive heart failure patients under milrinone administration
Shah R; Bekker A; Reisman S
2000 ;26th:49-50, Proceedings of the ... IEEE ... Annual Northeast Bioengineering Conference
— id: 47444, year: 2000, vol: 26th, page: 49, stat: Journal Article,

A PC-based graphical simulator for comparison of hemodynamic effects and myocardial energetics of cardiotropic drugs
Bekker A; Rim J; Wolk; Turndorf H
1999 ;15:524-524, Journal of clinical monitoring
— id: 47307, year: 1999, vol: 15, page: 524, stat: Journal Article,

Computer simulation of intracranial pressure changes during induction of anesthesia: comparison of thiopental, propofol, and etomidate
Bekker AY; Mistry A; Ritter AA; Wolk SC; Turndorf H
1999 Apr;11(2):69-80, Journal of neurosurgical anesthesiology
We have developed a computer model of cerebrovascular hemodynamics that interacts with a pharmacokinetic drug model. We used this model to examine the effects of various stimuli occurring during anesthesia on cerebral blood flow (CBF) and intracranial pressure (ICP). The model is a seven-compartment constant-volume system. A series of resistances and compliances relate blood and cerebrovascular fluid fluxes to pressure gradients between compartments. Variable arterial-arteriolar resistance (Ra-ar) and arteriolar-capillary resistance (Rar-c) simulate autoregulation and drug effects, respectively. Rar-c is also used to account for the effect of CO2 on the cerebral circulation. A three-compartment pharmacokinetic model predicts concentration-time profiles of intravenous induction agents. The effect-site compartment is included to account for disequilibrium between drug plasma and biophase concentrations. The simulation program is written in VisSim dynamic simulation language for an IBM-compatible personal computer. Using the model, we have predicted ICP responses during induction of anesthesia for a simulated patient with normal as well as elevated ICP. Simulation shows that the induction dose of intravenous anesthetic reduces ICP up to 30% (propofol > thiopental > etomidate). The duration of this effect is limited to less than 5 minutes by rapid drug redistribution and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension, exceeding the initial ICP. ICP elevation is more pronounced in a nonautoregulated cerebral circulation. Simulation results are in good agreement with the available experimental data. The presented model allows comparison of various drug administration schedules to control ICP
— id: 6097, year: 1999, vol: 11, page: 69, stat: Journal Article,

Remifentanil-N2O anesthesia shortens recovery time of cognitive function compared to isoflurane-fentanyl-N2O anesthesia in elderly patients
Bekker, AY; Berklayd, PM; Osborn, I; Sharma, S; Turndorf, H
1999 SEP ;91(3A):U128-U128, Anesthesiology
— id: 53862, year: 1999, vol: 91, page: U128, stat: Journal Article,

Comparative effects of cardiotropic drugs on hemodynamic and myocardial energetics. A computer simulation
Bekker, AY; Rim, J; Turndorf, H
1999 SEP ;91(3A):U270-U270, Anesthesiology
— id: 53864, year: 1999, vol: 91, page: U270, stat: Journal Article,

Computer simulation of cerebrovascular responses during induction of anesthesia: comparison of thiopental, propofol, and etomidate
Bekker A; Mistry A; Turndorf H; Osborn I; Wolk S; Kristoll D; Ritter A
1998 ;14:511-511, Journal of clinical monitoring & computing
— id: 47280, year: 1998, vol: 14, page: 511, stat: Journal Article,

Computer analysis of cerebrovascular hemodynamics during induction of anesthesia
Bekker A; Wolk S; Turndorf H; Ritter A
Simulators in anesthesiology education New York : Plenum Press, 1998,
— id: 3378, year: 1998, vol: , page: 121, stat: Chapter,

Computer simulation of cerebrovascular circulation: assessment of intracranial hemodynamics during induction of anesthesia
Bekker A; Wolk S; Turndorf H; Kristol D; Ritter A
1996 Nov;12(6):433-444, Journal of clinical monitoring
OBJECTIVE: The purpose of this project was to develop a computer model of cerebrovascular hemodynamics interacting with a pharmacokinetic drug model to examine the effects of various stimuli on cerebral blood flow and intracranial pressure during anesthesia. METHODS: The mathematical model of intracranial hemodynamics is a seven-compartment, constant-volume system. A series of resistance relate blood and cerebrospinal fluid fluxes to pressure gradients between compartments. Arterial, venous, and tissue compliance are also included. Autoregulation is modeled by transmural pressure-dependent, arterial-arteriolar resistance. The effect of a drug (thiopental) on cerebrovascular circulation was simulated by a variable arteriolar-capillary resistance. Thiopental concentration was predicted by a three-compartment, pharmacokinetic model. The effect site compartment was included to account for a disequilibrium between drug plasma and biophase concentrations. The model was validated by comparing simulation results with available experimental observations. The simulation program is written in VisSim dynamic simulation language for an IBM-compatible PC. RESULTS: The model developed was used to calculate the cerebral blood flow and intracranial pressure changes that occur during the induction phase of general anesthesia. Responses to laryngoscopy and intubation were predicted for simulated patients with elevated intracranial pressure and non-autoregulated cerebral circulation. Simulation shows that the induction dose of thiopental reduces intracranial pressure up to 15%. The duration of this effect is limited to less than 3 minutes by rapid redistribution of thiopental and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension, exceeding the initial intracranial pressure. Further simulation predicts that this untoward effect can be minimized by an additional dose of thiopental administered immediately prior to intubation. CONCLUSION: The presented simulation allows comparison of various drug administration schedules to control intracranial pressure and preserve cerebral blood flow during induction of anesthesia. The model developed can be extended to analyze more complex intraoperative events by adding new submodels
— id: 12480, year: 1996, vol: 12, page: 433, stat: Journal Article,

Anesthetic considerations for cerebral aneurysm surgery
Bekker AY; Baker KZ; Baker CJ; Young WL
1995 ;22(5):248-258, American journal of anesthesiology
— id: 8113, year: 1995, vol: 22, page: 248, stat: Journal Article,

Transient analysis of macromolecular blood-tissue exchange in microvascular bed [dissertation]
Bekker, Alex Yefim
[s.l.] : New Jersey Institute of Technology, 1987,
— id: 837, year: 1987, vol: , page: , stat: ,