Ahmed F. Ghouri

Effect of Flumazenil on Recovery after Midazolam and Propofol Sedation

BackgroundFlumazenil, a benzodiazepine antagonist, reverses midazolam-induced sedation and amnesia. We designed a double-blind study to evaluate the effects of flumazenil on patient outcome when flumazenil was used to reverse large or small doses of midazolam as part of standardized monitored anesthesia care. MethodsNinety-nine healthy consenting women undergoing breast biopsy procedures with local anesthesia were randomly assigned to one of four treatment groups: group 1, propofol-placebo (control); group 2, propofol-flumazenil; group 3, midazolam-placebo; or group 4, midazolam-flumazenil. All patients received intravenous midazolam 2 mg and intravenous fentanyl 50 μg, followed by an infusion of either propofol 25–150 μg-kg−1. min−1 or midazolam 0.5–4 μg · kg−1. min−1. At the end of the operation, patients were intravenously administered either 10 ml saline (groups 1 and 3) or flumazenil 1 mg in 10 ml saline (groups 2 and 4). Amnesia was assessed by determining recall of pictures shown before and after the procedure. Subjective feelings of sedation, anxiety, clumsiness, and fatigue were evaluated using 100-mm visual analogue scales preoperatively and at 30-min intervals in the recovery room. Cognitive function was assessed using the digit-symbol substitution test at similar intervals. Early recovery was evaluated by the ability of the patients to be transferred directly from the operating room to the step-down unit, as well as by times to ambulation and discharge. A standardized questionnaire and telephone interview were used to assess “resedation” and other postdischarge side effects. ResultsFlumazenil (1 mg) enhanced early recovery and picture recall after high-dose (group 4) but not low-dose (group 2) midazolam. Only 32% of patients in group 3 were transferred directly to the step-down unit compared with 85% in group 4 (P < 0.05). Flumazenil significantly improved visual analogue scale and digit-symbol substitution test scores at the 30− and 60-min testing intervals (P < 0.05). At the 90-min interval, there were no significant differences between groups 3 and 4. Compared with group 3 (84 ± 22 min), patients in groups 1, 2, and 4 were ready for discharge significantly earlier (60 ± 23, 65 ± 21, and 67 ± 27 min, respectively) (P < 0.05). However, 33% of the patients in group 4 reported resedation after discharge (vs. 0–8% in the other three study groups) (P < 0.05). ConclusionsEarly recovery after breast biopsy procedures with midazolam sedation and flumazenil reversal is similar to recovery after propofol sedation. However, the beneficial effects of flumazenil were apparent only during the first 60 min after the procedure and resedation after discharge is an important consideration in the outpatient setting.

Effect of fentanyl and nitrous oxide on the desflurane anesthetic requirement.

The minimum alveolar anesthetic concentration (MAC) of desflurane (I-653) was determined when administered with 60% nitrous oxide (N2O) in oxygen after a standardized induction sequence consisting of 0, 3, 6, or 9μg/kg intravenous (IV) fentanyl followed by 3–6 mg/kg IV thiopental and 1.5 mg/kg IV succinylcholine. For comparison, we also determined the isoflurane MAC with 60% N2O in oxygen after an induction dose of 3μg/kg IV fentanyl and similar doses of thiopental and succinylcholine. All patients were undergoing elective surgical procedures. The minimum alveolar anesthetic concentration in patients given isoflurane and 60% N2O with 3 μg/kg fentanyl was 0.4%, approximately 20% below previously reported MAC values for isoflurane with 60% N2O alone. The minimum alveolar anesthetic concentration of desflurane with 60% N2O plus 0, 3, 6, and 9μg/kg IV fentanyl was 3.7%, 3.0%, 1.2%, and 0.1%, respectively. Thus, the MAC‐lowering effect of 3μg/kg IV fentanyl appears to be similar with both isoflurane and desflurane. Fentanyl, 3–9μg/kg IV, produces dose‐dependent decreases in the MAC of desflurane.

Electroencephalogram spectral edge frequency, lower esophageal contractility, and autonomic responsiveness during general anesthesia

Both the electroencephalogram (EEG) spectral edge frequency (SEF) and lower esophageal contractility (LEC) indices have been reported to be useful indicators of anesthetic depth. We designed a prospective study to evaluate the relationship between changes in these two variables and objective measurements of physiologic responsiveness to surgical stress (i.e., changes in hemódynamic variables and plasma levels of norepinephrine, epinephrine, total catecholamines, and vasopressin). Eighty-nine consenting adult males undergoing radical prostatectomy procedures under a standardized general anesthetic technique were studied according to a randomized, single-blinded protocol. General anesthesia was induced with 30 µg/kg intravenous (IV) alfentanil, 2.5 mg/kg IV thiopental, and 0.1 mg/kg IV vecuronium, and subsequently maintained with 0.5 µg/kg/min alfentanil, nitrous oxide (N2O) 67% in oxygen, and 0.8 µg/kg/min vecuronium. Following retropubic dissection, 81 patients (92%) manifested acute hypertensive responses, with mean arterial pressure increasing from 90±14 to 122±14 mm Hg (mean ± SD). This acute hypertensive response was treated with one of three different treatment modalities (20 to 60 µg/kg IV alfentanil, 0.5 to 2.0% inspired isoflurane, or 0.05 to 0.15 mg/kg IV trimethaphan) to return the mean arterial pressure to within 10% of the preincisional (baseline) value within 5 to 10 minutes. Although the mean arterial pressure, heart rate, and plasma levels of catecholamines and vasopressin significantly increased following the surgical stimulus, and decreased after adjunctive therapy, the EEG-SEF and LEC index (LECI) values did not significantly change during these study intervals. Furthermore, using a logistic regression analysis, we observed that preincision EEG-SEF and LECI values could not predict whether patients would manifest a hypertensive response. Therefore, the EEG-SEF and LECI were unreliable indicators of anesthetic depth.

Accidental intraarterial drug injections via intravascular catheters placed on the dorsum of the hand.

IMPLICATIONS Two cases of placement of a catheter in the dorsum of a hand into an artery mistaken to be a vein are described. Diagnosis and treatment of such mishaps are discussed.

Prediction of occult neck disease in laryngeal cancer by means of a logistic regression statistical model

The ability to accurately predict the presence of subclinical metastatic neck disease in clinically N0 patients with primary epidermoid cancer of the larynx would be of great value in determining whether to perform an elective neck dissection. We describe a statistical approach to estimating the probability of occult neck disease given pretreatment clinical parameters. A retrospective study was performed involving 736 clinically N0 patients with primary laryngeal cancer who were treated surgically with primary resection and ipsilateral neck dissection. Nodal involvement was determined histologically after surgical lymphadenectomy. A logistic regression model was used to derive an equation that calculated the probability of occult neck metastasis based on pretreatment T stage, tumor location, and histologic grade. The model has a sensitivity of 74%, a specificity of 87%, and can be entered into a programmable calculator.

Comparative effects of desflurane and isoflurane on vecuronium-induced neuromuscular blockade

STUDY OBJECTIVE To evaluate the neuromuscular effects of a nondepolarizing muscle relaxant (vecuronium) during anesthesia with equipotent concentrations of either desflurane or isoflurane. DESIGN Randomized open study comparing effects of desflurane and isoflurane on vecuronium-induced neuromuscular blockade. SETTING University-affiliated medical center. PATIENTS Forty-five healthy adults undergoing elective surgical procedures randomly assigned to receive either desflurane, nitrous oxide (N2O), and vecuronium or isoflurane, N2O, and vecuronium for maintenance of general anesthesia. INTERVENTIONS Following a standardized induction sequence, patients receiving either desflurane and N2O or isoflurane and N2O were administered bolus doses of vecuronium equal to 0.01, 0.02, or 0.03 mg/kg intravenously (IV) during the maintenance period. Neuromuscular transmission was measured using a Relaxograph monitor. MEASUREMENTS AND MAIN RESULTS Vecuronium produced similar depression of neuromuscular function at equipotent (50% of the minimum alveolar concentration) end-tidal concentrations of isoflurane 0.6% and desflurane 3.0%. Following administration of vecuronium 0.01 to 0.03 mg/kg IV, onset times (3.4 +/- 0.4 minutes to 3.2 +/- 0.4 minutes and 3.2 +/- 0.5 minutes to 3.0 +/- 0.6 minutes), maximum T1 twitch depression (80% +/- 10% to 95% +/- 9% and 81% +/- 9% to 97% +/- 10%), clinical duration of blockade (12 +/- 5 minutes to 20 +/- 8 minutes and 10 +/- 5 minutes to 19 +/- 17 minutes), and T1 recovery times (10 +/- 3 minutes to 12 +/- 6 minutes and 10 +/- 3 minutes to 12 +/- 4 minutes) were similar in the isoflurane and desflurane treatment groups, respectively (means +/- SD). CONCLUSION Vecuronium has similar neuromuscular effects when administered in the presence of desflurane 3% and isoflurane 0.6%.

Epidermoid carcinoma of the oral cavity and oropharynx: validity of the current AJCC staging system and new statistical tools for the prediction of subclinical neck disease.

The 1983 and 1988 AJCC T- and N-staging systems were compared using the case records of 531 patients with primary epidermoid malignancies of the oral cavity. All patients had a minimum followup of 5 years. There were 390 patients with early stage (T1, T2) disease and 141 with advanced stage (T3, T4) lesions according to both the 1983 and 1988 T-definitions: 342 patients manifested no clinical nodes (NO), 189 had clinically evident nodes (N1-N3), and none had metastatic disease. Cox regression analysis demonstrated that the 1983/1988 T-stage definitions differentiated survival successfully (p < 0.001). The 1988 staging system for nodal disease showed a highly significant separation of N2 and N3 when compared with the 1983 system (p < 0.001). Of the 342 patients who were staged NO, 154 had primary neck dissection. Logistic regression predicted the incidence of subclinical disease according to the site and the T-stage of the primary tumor with a sensitivity of 78% and a specificity of 95%. We conclude that the 1988 N-stage definition is a better prognosticator of survival than the 1983 definition. Furthermore, a logistic regression model can be used to predict the probability of subclinical disease in primary oral cavity cancers.

Clinical pharmacokinetics of anaesthetic drugs: an overview

Summary Why study pharmacokinetics and dynamics? As anaesthetic drugs and administration techniques become increasingly sophisticated, objective descriptions of their physiological and pharmacological properties will assume even greater importance. This understanding will not only provide for improved delivery and titration of anaesthetic drugs to produce the desired clinical effects, but will also provide insights into their mechanisms of action and lead to the development of safer and more efficacious drugs for use in the future. Indeed, whether one is referring to drug disposition (kinetics) or biological effects (dynamics), accurate measurements must be our first priority. Since, as elegantly stated by Lord Kelvin: ‘measurement is the basis of all knowledge’.