A Phase IIIb, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of dexmedetomidine for sedation during awake fiberoptic intubation.

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.

Monitored anesthesia care with dexmedetomidine: a prospective, randomized, double-blind, multicenter trial.

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.

Evaluation of aromatherapy in treating postoperative pain: pilot study.

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).

A double-blind prospective comparison of rofecoxib vs ketorolac in reducing postoperative pain after arthroscopic knee surgery.

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.

Dexmedetomidine in awake craniotomy: a technical note.

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.

Dexmedetomidine for awake carotid endarterectomy: efficacy, hemodynamic profile, and side effects.

: 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.

Cognitive function after anaesthesia in the elderly.

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.