Epidural block for obstetrics: Comparison of bolus injection of local anesthetic with gravity flow technique

Study Objective: To test the hypothesis that slow administration of local anesthetic into the epidural space by gravity flow reduces the incidence of signs and symptoms of unintended injection.

Design: Prospective, randomized study.

Setting: Teaching hospital.

Patients: 600 ASA physical status I and II parturients scheduled for labor and delivery or elective cesarean section.

Interventions: After identification of the epidural space with pulsations of an air-fluid column, parturients for vaginal delivery (n = 380) were randomized to receive a test dose of 3 ml 3% 2-chloroprocaine with epinephrine 20 μg, two doses of 7 ml bupivacaine 0.03 % with sufentanil 1 μg/ml and epinephrine 2 μg/ml by either gravity flow (Group 1) given over 30 seconds or by bolus injection (Group 2) given over 5 seconds through the epidural needle; parturients for Cesarean delivery (n = 220) were randomized to receive a test dose and two doses of 6 ml lidocaine 2 % with sufentanil 1 μg/ml and epinephrine 2 μg/ml by either gravity flow or by bolus injection through the epidural needle. Changes in maternal heart rate (HR) and blood pressure, signs of intravascular injection, and adverse effects of epidural bupivacaine-sufentanil were recorded after each dose.

Measurements and Main Results: Gravity flow administration (Group 1) was associated with a smaller increase in mean maternal HR (p < 0.001), less hypotension (p < 0.01), sedation (p < 0.01), nausea (p = 0.01), and segmental spread (p < 0.0001) than were corresponding doses given by traditional bolus injection (Group 1) for vaginal or Cesarean deliveries. The incidence of systemic toxicity was zero of 300 (0%) with gravity flow and 4 of 300 (1.3%) by bolus injection, p = 0.12, Fisher's exact test. No patient in either group had an accidental intrathecal injection.

Conclusion: Gravity flow administration of local anesthetic-opioid solution during epidural block for obstetrics was associated with fewer signs of systemic drug absorption and cardiovascular perturbations than was the traditional bolus injection. This study supports the current opinion that slow administration of local anesthetic during epidural black contributes to fewer adverse events.     

Time to peak effect of neostigmine at antagonism of atracurium- or vecuronium-induced neuromuscular block

Study Objective: (1) To determine the time to peak effect of neostigmine (time to peak antagonism) during atracurium- or vecuronium-induced neuromuscular block; and (2) to determine the effect on time to peak effect of neostigmine during atracurium-induced neuromuscular block, when the dose of neostigmine is increased from 35 μg/kg to 70 μg/kg.

Design: Prospective, randomized clinical study.

Setting: Gynecologic operating room suite at a university hospital.

Patients: 45 ASA I and II women admitted for gynecologic laparotomy.

Interventions: Anesthesia was performed with thiopental sodium, fentanyl, halothane, nitrous oxide, and atracurium or vecuronium. Train-of-four (TOF) stimulation and mechanomyography were used to monitor neuromuscular transmission. Neostigmine was administered while a constant degree of neuromuscular block was maintained at a twitch height at a point between 4% and 11% of the control twitch height, using a continuous infusion of atracurium or vecuronium. The patients were randomized to three groups, with 15 patients in each group. Group 1 received atracurium block antagonized with neostigmine 35 μg/kg; group 2 received vecuronium block antagonized with neostigmine 35 μg/kg; and group 3 received atracurium block antagonized with neostigmine 70 μg/kg.

Measurements and Main Results: The degree of neuromuscular block at antagonism was similar in the three groups. Time to peak effect (mean ± SD) on TOF ratio was significantly longer in Group 1 (9.7 ± 3.0 minutes) versus Group 2 (6.6 ± 1.4 minutes; (p < 0.05). The time to peak effect on TOF ratio during atracurium-induced block was reduced from 9.7 ± 3.0 minutes to 6.3 ± 2.0 minutes when the dose of neostigmine was increased from 35 μg/kg to 70 μg/kg (p < 0.05). The peak effect on TOF ratio was significantly greater in Group 3 compared with Group 1 (p < 0.05), while it was similar in groups 1 and 2.

Conclusion: The time to peak effect of neostigmine 35 μg/kg is about 6 to 10 minutes when antagonizing a constant degree of atracurium- or vecuronium-induced neuromuscular block at a twitch height at a point between 4% and 11%. Even though the time to peak effect was longer with atracurium than with vecuronium, clinically significant differences between the antagonizing effect of atracurium versus vecuronium block were not demonstrated. The time to peak effect during atracurium-induced block decreased when the dose of neostigmine was increased from 35 μg/kg to 70 μg/kg.     

Pretreatment with sedative-hypnotics, but not with nondepolarizing muscle relaxants, attenuates alfentanil-induced muscle rigidity

Study Objective: To evaluate and compare the efficacy of various pretreatment agents to attenuate or prevent opioid-induced muscle rigidity using a well-established, previously described clinical protocol.

Design: Prospective, controlled, single-blind, partially randomized study.

Setting: Large medical center.

Patients: ASA physical status I–III patients undergoing elective surgical procedures of at least 3 hours' duration.

Interventions: The effect of pretreatment with nondepolarizing muscle relaxants (atracurium 40μg/kg or metocurine 50,μg/kg), benzodiazepine agonists (diazepam 5 mg or midazolam 2.5 mg), or thiopental sodium 1 mg/kg on the increased muscle tone produced by alfentanil 175 ,μg/kg was compared with a control group (given no pretreatment).

Measurements and Main Results: Rigidity was assessed quantitatively by measuring the electromyographic activity of five muscle groups (biceps, intercostals, abdominals, quadriceps, and gastrocnemius). Rigidity also was rated qualitatively by attempts to initiate and maintain mask ventilation, attempts to flex an extremity, and the occurrence of myoclonic movements. Pretreatment with the two nondepolarizing muscle relaxants had no effect on the severe muscle rigidity produced by high-dose alfentanil. Whereas thiopental was only mildly effective, the benzodiazepines midazolam and diazepam significantly attenuated alfentanil rigidity (p < 0.05).

Conclusion: This study suggests that benzodiazepine pretreatment is frequently, but not always, effective in preventing opioid-induced muscle rigidity.     

The induction, maintenance, and recovery characteristics of spinal versus general anesthesia in elderly patients

Study Objective: To compare the induction and recovery profiles of three combinations of general anesthesia when used as an alternative to spinal anesthesia for elderly patients.

Design: Randomized, prospective, open-label study.

Setting: Large referral hospital.

Patients: 100 [ASA physical status I, II, and III] patients over 60 years of age undergoing brief transurethral surgery.

Interventions: In Groups Propofol-Propofol (P-P), Propofol-Isoflurane (P-I), and Propofol-Desflurane (P-D), anesthesia was induced with fentanyl (1 to 2 μg/kg IV) and propofol (1.0 to 2.0 mg/kg IV) and maintained with 70% nitrous oxide in oxygen and either a propofol infusion (75 to 150 μg/kg/min) or isoflurane (end-tidal 0.7% to 1.2%) or desflurane (end-tidal 1% to 4%), respectively. After induction, a laryngeal mask airway was placed and spontaneous ventilation was maintained. In Group Spinal (S), 1.5 ml 4% lidocaine (60 mg), in an equal volume of 10% dextrose, was administered intrathecally.

Measurements and Main Results: Induction and recovery characteristics were compared. Induction with propofol was technically easier and significantly (medp < 0.0001) faster (4.6 ± 1.7 min, 4.7 ± 2.2 min, and 3.8 ± 1.4 min for Groups P-P, P-I, and P-D, respectively) than induction of spinal anesthesia (9.3 ± 3.4 min). During the induction period, mean arterial blood pressure and heart rate were significantly higher in Group S. Emergence, extubation, and orientation times were similar among the general anesthesia treatment groups. In Group S, patient-generated pain scores were lower (p < 0.05) and recovery room admission longer (p < 0.001). Time to return to baseline digit symbol substitution test (DSST) scores was marginally improved in Groups P-P and P-D when compared to Group P-I. Postoperative nausea, sleepiness, anxiety, and coordination were unaffected by the treatment modality.

Conclusion: General anesthesia with propofol and desflurane facilitates shorter induction and recovery times without adversely affecting patient comfort. Therefore, this technique may be preferable to spinal anesthesia for elderly patients undergoing short transurethral surgical procedures.     

Propofol and alfentanil for sedation during placement of retrobulbar block for cataract surgery

Study Objective: To determine if the addition of alfentanil to propofol is more effective than propofol alone to provide adequate conditions for placement of a retrobulbar block prior to cataract surgery.Design: Randomized, double-blinded study.Setting: Outpatients at a university hospital.Patients: 40 adult ASA physical status I, II, and III outpatients scheduled for elective cataract surgery.Interventions: Patients were randomly assigned to receive one of four drug combinations prior to the placement of a retrobulbar block: Group 1, propofol alone; Group 2, alfentanil 5 μg/kg plus propofol; Group 3, alfentanil 10 μg/kg plus propofol; Group 4, alfentanil 15 μg/kg plus propofol. All patients were preoxygenated by face mask for two minutes prior to drug administration. The quality of conditions for block placement were determined by: (1) assessing the amount of movement by the patients while the block needle was in place, (2) cooperativeness of the patients during the operation, (3) hemodynamic side effects, (4) incidence and severity of respiratory depression, (5) incidence of nausea and vomiting, (6) recall of placement of the block, and (7) time to discharge from the hospital.Measurements and Main Results: The addition of alfentanil to propofol for sedation prior to placement of the retrobulbar block resulted in a dose-dependent reduction in movement by the patients. However, the highest dose of alfentanil (15 μg/kg) resulted in the greatest frequency (40% of the patients in this group) of respiratory depression (SpO₂ < 90%). All patients were cooperative during the operation and responsive to verbal command within 5 minutes of placement of the block. In addition, all of the patients denied being nauseated, having vomited, or recalling block placement in the recovery room or the next day.Conclusions: The combination of alfentanil and propofol may be used to sedate patients in order to limit movement and provide a cooperative, alert patient with stable hemodynamics and limited respiratory depression during placement of retrobulbar block prior to ophthalmic surgery. However, excessive dosage of these drugs may result in hazardous respiratory depression in this patient population.     

Subarachnoid bupivacaine blockade decreases midazolam and thiopental hypnotic requirements

Study Objective: To test the hypothesis that subarachnoid bupivacaine blockade decreases hypnotic requirements for thiopental sodium and midazolam.

Design: Randomized, double-blind, placebo-controlled study.

Setting: Teaching hospital.

Patients: 53 nonpremedicated ASA physical status I and II adult male patients scheduled for elective lower abdominal, pelvic, or lower limb surgery.

Interventions: Intravenous injections of midazolam or thiopental were administered with or without subarachnoid bupivacaine blockade (12.5 mg) at the L₃–L₄ level. Thiopental or midazolam hypnotic requirements were determined using loss of ability to open eyes in response to verbal command as an endpoint. The thiopental requirements were determined by titration; the midazolam requirements were determined from dose-response curves obtained with bolus injections of predetermined doses of the drug.

Measurements and Main Results: Subarachnoid bupivacaine blockade decreased the hypnotic dose of thiopental from 3.40 ± 0.68 mg/kg (mean ± SD) with a dose range of 2.3 to 4.5 mg/kg (intramuscular saline) to 2.17 ± 0.48 mg/kg with a dose range of 1.3 to 2.8 mg/kg (p < 0.005 for the difference). The ED₅₀ value of midazolam decreased with the bupivacaine blockade, from 0.23 mg/kg (95% confidence limits: 0.08 to 0.38 mg/kg) to 0.06 mg/kg (0.01 to 0.14 mg/kg), with p < 0.0001 for the difference.

Conclusion: Subarachoid bupivacaine blockade decreases hypnotic requirements for both thiopental and midazolam. The results suggest that the reduction in hypnotic requirements is due to the decrease in afferent input induced by spinal anesthesia.     

Patient-controlled drug administration during local anesthesia: A comparison of midazolam, propofol, and alfentanil

Study Objective: To evaluate the perioperative effects of alfentanil, midazolam, and propofol when administered using a patient-controlled analgesia (PCA) device during local anesthesia.

Design: Randomized, single-blind comparative study.

Setting: Outpatient surgery center at a university teaching hospital.

Patients: Ninety outpatients undergoing minor elective surgical procedures with local anesthetic infiltration were assigned to one of three treatment groups.

Interventions: After premedication with midazolam 1 mg intravenously (IV) and fentanyl 50 μg IV, patients were allowed to self-administer 2 ml bolus doses of either alfentanil 250 μg/ml, midazolam 0.4 mg/ml, or propofol 10 mg/ml at minimal intervals of 3 minutes to supplement a basal infusion rate of 5 ml/hr.

Measurements and Main Results: The total intraoperative dosages of alfentanil, midazolam, and propofol were 2.7 ± 1.1 mg, 4.7 ± 2.7 mg, and 114 ± 42 mg, respectively, for procedures lasting 48 ± 28 minutes to 51 ± 19 minutes (means ± SD). Propofol produced more pain on injection (39% vs. 4% and 6% in the alfentanil and midazolam groups, respectively). Episodes of arterial oxygen saturation less than 90% were more frequent with alfentanil (28%) than with midazolam (3%) or propofol (13%). Using the visual analog scale, patients reported comparable levels of discomfort, anxiety, and sedation during the operation in all three treatment groups. Postoperative picture recall was significantly decreased with midazolam versus alfentanil and propofol. Finally, postoperative nausea was reported more frequently in the alfentanil group (29%) than in the midazolam (10%) or propofol (18%) groups, contributing to a significant prolongation of the discharge time in the alfentanil-treated patients.

Conclusions: When self-administered as adjuvants during local anesthesia using a PCA delivery system, alfentanil, midazolam, and propofol were equally acceptable to patients. However, propofol and midazolam were associated with fewer perioperative complications than was alfentanil.     

Effects of prostaglandin E1 on the cardiovascular response to tracheal intubation

Study Objective: To evaluate the efficacy of prostaglandin E, in attenuating the hypertensive response to laryngoscopy and intubation.

Design: Controlled, comparative, and randomized study.

Setting: Induction of anesthesia for elective surgery at a university hospital.

Patients: Thirty normotensive patients (ASA physical status I) undergoing elective surgery divided into three groups. Each group consisted of ten patients.

Interventions: Anesthesia was induced with thiopental sodium 5 mglkg intravenously, and tracheal intubation was facilitated with vecuronium 0.2 mglkg. Either 0.3 μglkg of prostaglandin E₁, 0.6 μg/kg of prostaglandin E₁, or saline (control) was injected 15 seconds before starting direct laryngoscopy (within 30 seconds), which was attempted 2 minutes after administration of thiopental sodium and vecuronium.

Measurements and Main Results: Patients receiving saline showed a significant increase in mean arterial pressure and rate-pressure product associated with tracheal intubation. These increases following tracheal intubation were significantly less in prostaglandin E₁-treated patients than in the control group (p < 0.05).

Conclusions: A single rapid intravenous administration of prostaglandin E₁ is a practical pharmacologic and safe method to attenuate the hypertensive response to tracheal intubation. The use of 0.6 μglkg of prostaglandin E₁ as a supplement during induction is recommended for reducing the pressor response to intubation on the basis of rate-pressure product and mean arterial pressure , following intubation as an index.     

Intravenous Phenylephrine Preconditioning of Cardiac Grafts From Non–Heart-Beating Donors

Background. Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heart-beating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning.

Methods. Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 μg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia.

Results. Phenylephrine 25 μg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 ± 0.5 versus 7.7 ± 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 ± 5.3 versus 41.0 ± 3.4 mm Hg; p = 0.04). Phenylephrine 25 μg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09).

Conclusions. Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.     

Ketorolac or fentanyl to supplement local anesthesia?

Study Objective: To evaluate the usefulness of ketorolac in the treatment of intraoperative pain refractory to the administration of local anesthetic alone.

Design: Intraoperative acute-pain treatment model consisting of awake, nonsedated patients who randomly received either an opioid or a study drug in a double-blind fashion.

Setting: University medical center.

Patients: Eighty patients who underwent breast biopsy, lumpectomy, or central venous catheter placement.

Interventions: Patients received either ketorolac 1 mg/kg intravenously (IV) up to a total dose of 60 mg or fentanyl 3 μg/kg IV up to a total dose of 250 μg to supplement the local anesthetic.

Measurements and Main Results: Verbal pain evaluation and the visual analog scale (VAS) were used for perioperative measurement of pain. Heart rate (HR), blood pressure, and respiratory rate (RR) were recorded before and after analgesic drug injections at 10-minute intervals, both intraoperatively and while the patient was in the postanesthesia care unit (PACU). Speed of recovery was quantified by p-deletion and digit substitution tests on admission to the PACU and at 30-minute intervals until discharge. The frequency of nausea, vomiting, and pruritus were recorded. There were no differences between the groups in perioperative verbal pain evaluation, VAS scores, HR, systolic blood pressure, diastolic blood pressure, or RR. Patients who received ketorolac exhibited a significantly lower frequency of intraoperative and postoperative medication administration intraoperatively, than those who received fentanyl. No additional pain medication was required by patients in the PACU in either group.

Conclusions: Ketorolac is a useful alternative to fentanyl for the treatment of intraoperative pain refractory to the administration of local anesthetic alone during monitored anesthesia care. A decided advantage of ketorolac over fentanyl is the absence of nausea and vomiting in the intraoperative and postoperative periods.     

Effects of diltiazem on renin-aldosterone and ACTH-adrenocortical function during upper abdominal surgery

Study Objective: To observe the effects of continuous intravenous infusion of diltiazem on the renin-aldosterone system and ACTH-adrenocortical axis responses during surgical stimulation.

Design: Randomized study of intravenous diltiazem.

Setting: Operating room at the Hyogo Medical College Hospital.

Patients: Twenty-three patients undergoing upper abdominal surgery were divided into two groups: the control group (n = 10) and the diltiazem group (n = 13). All the patients were without any complications and classified as ASA physical status I.

Interventions: Patients in the diltiazem group received an infusion of 10 μg/kg/ min for 90 to 120 minutes following skin incision.

Measurements and Main Results: Plasma adrenocorticotropic hormone, plasma aldosterone and cortisol concentrations, and plasma renin activity were determined with radioimmunoassay before the induction of anesthesia at 10, 30, 60, and 90 minutes after skin incision and at the end of anesthesia. Renin activity did not change significantly. Maximal increases in plasma adrenocorticotropic hormone, aldosterone, and cortisol observed 90 minutes after skin incision were 355 ± 95 pg/ml, 118 ± 30 pg/ml, and 14.2 ± 2.3 μg/dl in the control group versus 246 ± 41 pg/ml, 119 ± 25 pg/ml, and 15.0 ± 1.8 μg/dl in the diltiazem group, respectively, and there were no significant differences between these groups. Adrenocorticotropic hormone was significantly lower in the diltiazem group compared with that in the control group 60 minutes after the start of surgery (p < 0.05). There was marked natriuresis (40 ± 25 μEq/min vs 470 ± 147 μEq/min at the 90-minute mark) and diuresis (0.16 ± 0.13 ml/min vs. 2.53 ± 0.88 ml/min) in the diltiazen group.     

Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia

Background. Therapeutic angiogenesis in ischemic myocardium has been shown to be a feasible and effective strategy to improve regional blood flow and myocardial function. However, the optimal mode of growth factor administration still needs to be established.

Methods. Using a pig model of chronic myocardial ischemia, we evaluated the efficacy of intravenous and intracoronary infusion of FGF-2 at 2 and 6 μg/kg compared with a vehicle control. Improvement in myocardial perfusion and function was assessed by angiography, colored microspheres, and function and perfusion magnetic resonance imaging.

Results. Intracoronary 6-μg/kg FGF-2 increased angiographic collaterals (p = 0.046) and increased regional blood flow to the ischemic area from 0.36 ± 0.07 to 0.59 ± 0.08 mL/min/g at stress (vs control, p = 0.032). Also, after 6 μg/kg intracoronary FGF-2, ejection fraction, regional wall motion, and thickening improved significantly by 9.9% ± 1.9%, 126% ± 39%, and 13.8% ± 3.6%, respectively. Intravenous FGF-2 and intracoronary 2 μg/kg FGF-2 were ineffective.

Conclusions. A single 6-μg/kg intracoronary treatment with FGF-2 resulted in significant improvement in collateralization and regional and global function of chronically ischemic myocardium. Single intravenous infusion of FGF-2 was not effective in this model.     

Alfentanil infusion in neurosurgical patients

Alfentanil administered by constant rate infusion was evaluated as a main anesthetic in craniotomy patients. Eleven patients (ASA II) received either an induction dose of 200 microg/kg alfentanil followed by a 1 microg/kg/min infusion, or a 150 microg/kg bolus followed by a 1.5 microg/kg/min infusion. The infusion was stopped at least 1 h before the end of surgery. In addition to routine clinical neuroanesthesia monitoring, cardiovascular parameters, extubation conditions, and recovery scores were systematically recorded. Plasma alfentanil levels were determined in all patients during and for 6 h after the infusion. Finally, pharmacokinetic studies were carried out in five patients from both groups. This technique provided a remarkable cardiovascular stability, excellent extubation conditions, a comfortable recovery period, and no signs of prolonged or recurrent narcotization. No difference in clinical signs or alfentanil blood concentrations between the two drug regimens could be found. Pharmacokinetic parameters found were comparable to those obtained after single bolus drug elimination. Despite large individual variations and sometimes very prolonged infusion, there was no evidence of delayed drug administration. All of the above findings warrant the use of alfentanil infusion in neuroanesthesia and confirm the unique pharmacological properties of this drug among existing narcotics.     

Comparison of nicardipine versus esmolol in attenuating the hemodynamic responses to anesthesia emergence and extubation

OBJECTIVE: The purpose of this study was to compare the effectiveness of intravenous (IV) nicardipine versus esmolol in controlling heart rate (HR) and blood pressure (BP) responses to emergence and extubation. DESIGN: Prospective, randomized, double blind. SETTING: University hospital, single institution. PARTICIPANTS: Twenty-two American Society of Anesthesiologists physical class 1 to 3 adult inpatients scheduled for general anesthesia. INTERVENTIONS: General endotracheal anesthesia with oxygen/isoflurane and muscle relaxation. At end of surgery, with at least 2 twitches by nerve stimulator and end-tidal isoflurane <0.4%, muscle relaxant reversal was accomplished with neostigmine and glycopyrrolate. Two minutes postreversal, the IV study drug nicardipine, 0.03 mg/kg, or esmolol, 1.5 mg/kg, was administered. HR and BP were measured every minute up to 10 minutes and at minute 15 postreversal. MEASUREMENTS AND MAIN RESULTS: There were no significant differences between groups in age, weight, gender, American Society of Anesthesiologists physical class or preoperative hemodynamics (HR, BP, mean arterial pressure [MAP]). Compared with nicardipine, 0.03 mg/kg IV, esmolol, 1.5 mg/kg IV, significantly (p < 0.05) attenuated HR more than nicardipine for the 15-minute time period poststudy drug. Compared with esmolol, nicardipine was significantly (p < 0.05) more effective in controlling MAP and systolic BP for the 1- to 3-minute and diastolic BP for the 1- to 2-minute time periods poststudy drug. There were no episodes of hypotension or adverse events. CONCLUSIONS: Although esmolol, 1.5 mg/kg, IV was more effective than nicardipine, 0.03 mg/kg, IV for attenuating the HR response to extubation, nicardipine was more effective in controlling the BP response.     

Pharmacodynamic effects of three doses of ORG 9426 used for endotracheal intubation in humans

Study Objective: To determine the pharmacodynamic characteristics of three incremental doses of ORG 9426 used for endotracheal intubation in patients.

Design: Double-blind, randomized administration of one of three doses of intravenous ORG 9426.

Setting: Inpatients requiring surgery at Georgetown University Medical Center.

Patients: Thirty-six patients, ages 18 to 65, ASA physical status I, II, and III, scheduled for general surgery.

Interventions: After Georgetown University Institutional Review Board approval and patient consent, patients were premeditated with midazolam or droperidol. Anesthesia was induced with thiopental sodium and fentanyl. Anesthesia was maintained with 60% nitrous oxide in oxygen. The ulnar nerve was stimulated supramaximally with a 2 Hz train-of four (TOF) every 20 seconds. Thumb contractions were measured with a force transducer. When TOF and anesthesia were stable, 2, 2.5, or 3 times the ED₉₅ of ORG 9426 (570 μg/kg 710 μg/kg or 850 μg/kg) was administered randomly. Tracheal intubation was attempted at maximal depression of the first TOF response (T₁).

Measurements and Main Results: The following parameters were measured: time interval from the injection of ORG 9426 to 90% depression of T₁ (T₁ 90% block), maximal T₁ depression (onset time), intubating conditions, clinical duration (time for return of T₁ to 25% of control), heart rate (HR), blood pressure (BP), and any adverse clinical experience. ORG 9426 provided adequate intubating conditions in all patients but two, independent of the dose used. Its onset time was rapid, but increasing the dose did not shorten the onset. T₁ 90% block was achieved rapidly (75 ± 25 seconds to 78 ± 18 seconds, means ± SD). The clinical duration of ORG 9426 was relatively short and lengthened with increasing doses (from 36 ± 18 minutes at 570 μg/kg to 42 ±10 minutes at 850 μg/kg. Spontaneous twitch recovery from 10% to 25% was similar in all dosage groups (5 ± 1 minutes to 6 ± 4 minutes). No clinically significant changes in HR and BP and no adverse clinical experiences were noted in any group.

Conclusion: These findings warrant further clinical evaluation of ORG 9426 for induction and maintenance of muscle relaxation in humans.     

Esmolol and cardiopulmonary bypass during reperfusion reduce myocardial infarct size in dogs

Background. Infarct size can be reduced by β-blockade in acute myocardial ischemia. However it is unknown whether myocardial salvage is still effective when β-blockade is limited to reperfusion.

Methods. After initiation of cardiopulmonary bypass, 20 dogs were submitted to 2 hours of regional left ventricular ischemia, followed by 2 hours of reperfusion. In 11 dogs β-blockade was started with the onset of reperfusion (esmolol group). The remaining dogs received no treatment (control, n = 9). Infarct size was determined by tetrazolium chloride staining. Myocardial water content (MWC) and ultrastructural damage (electronmicroscopy) were determined from transmural biopsies.

Results. Infarct size was significantly smaller in the esmolol group compared with control (49% versus 68%, p < 0.05). After 2 hours ischemia there was no difference in MWC between groups, whereas after 2 hours reperfusion MWC of ischemic myocardium was significantly lower in the esmolol group than in the control (p < 0.05). Ultrastructural changes were typical for ischemia-reperfusion injury in both groups.

Conclusions. β-Blockade may be cardioprotective during reperfusion through various mechanisms and may enhance myocardial salvage, even when treatment is initiated as late as with the onset of reperfusion.     

Remifentanil vs alfentanil in the total intravenous anaesthesia for paediatric abdominal surgery

BACKGROUNDS: Our aim was to investigate whether total intravenous anaesthesia (TIVA) with remifentanil and alfentanil would ensure appropriate analgesia and recovery conditions in anaesthesia for children undergoing abdominal surgery. METHODS: Sixty children, scheduled for abdominal operations were randomized to receive, in a double-blind manner, either remifentanil (loading dose 1 microg x kg(-1); maintenance infusion, 0.25 microg x kg(-1) min(-1)) or alfentanil (loading dose 50 microg x kg(-1); maintenance infusion, 1 microg x kg(-1) min(-1)) as the analgesic component of TIVA. They were combined with propofol (loading dose, 2 mg x kg(-1); step 1 maintenance infusion, 10 mg x kg(-1) h(-1); step 2 maintenance infusion, 8 mg x kg(-1) h(-1); step 3 maintenance infusion, 6 mg x kg(-1) h(-1)) neuromuscular blockade was with mivacurium. Dose changes of the drugs, the times from cessation of anaesthesia to extubation, verbal responses, recovery of ventilation, orientation, and qualification for discharge from the postanaesthetic care unit (PACU) were recorded. RESULTS: Demographics, duration of surgery and anaesthesia were similar between the two groups. Times to extubation and stay in the PACU were significantly shorter in the remifentanil group compared with the alfentanil group. Quality of emergence (QE) from anaesthesia scale scores were higher in the remifentanil group compared with the alfentanil group. CONCLUSIONS: Remifentanil provides a more rapid recovery and adequate postoperative analgesia after TIVA for paediatric abdominal surgery, compared with alfentanil.     

Spontaneous movements associated with rocuronium injection: The effects of prior administration of fentanyl

Study Objective: To determine if prior injection of fentanyl decreases the incidence of spontaneous movements during rocuronium administration.

Design: Prospective, randomized, double-blind, placebo-controlled study.

Setting: University orthopedic surgical center.

Patients: 122 ASA physical status I and II patients scheduled for elective orthopedic surgery.

Interventions: Patients randomly received 2 ug/kg of fentanyl or the equivalent volume of NaCl 0.9% 45 seconds prior to induction of anesthesia. Induction was performed with propofol 2.5 mg/kg followed by rocuronium 0.8 mg/kg 60 seconds later. Spontaneous movements were scored as follows: a) limited to the hand, b) limited to the elbow, and c) involving the whole arm, including the shoulder.

Measurements and Main Results: Prior injection of fentanyl (2 ug/kg) significantly decreased the incidence of spontaneous movements limited to the hand: 5% versus 20% (p < 0.05); limited to the elbow: 1 % versus 25% (p < 0.05); and involving the whole arm: none versus 12% (p < 0.05). No erythema or any change in the skin surrounding the point of injection of the involved arm was observed. Twenty-four hours later, no vein induration was present and no patient complained of any residual pain.

Conclusion: Prior injection of fentanyl significantly decreases the incidence of spontaneous movements associated with rocuronium administration.     

Esmolol promotes electroencephalographic burst suppression during propofol/alfentanil anesthesia.

This study examined the effects of an esmolol infusion on the electroencephalogram during propofol/alfentanil IV anesthesia. After informed consent, 20 patients were randomly assigned into four groups on the basis of two target alfentanil concentrations (alfentanil 50 or 150 ng/mL) and of a saline or esmolol infusion. Bispectral index (BIS), burst suppression ratio (SR), and physiologic variables were continuously monitored. A 30-min blinded infusion of saline or esmolol was started after establishing a stable baseline and followed by a washout period. The electroencephalogram was significantly suppressed by esmolol (BIS, 37 +/- 6 to 22 +/- 6, 40% decrease [mean +/- SD]; SR, 5 +/- 7 to 67 +/- 23, 13.4-fold increase) compared with baseline in the small-dose alfentanil groups. Discontinuation of esmolol reversed the response. BIS and SR were unaffected by placebo infusion. Twelve-minute to 16-min hysteresis between esmolol administration and the onset of half-maximal cortical suppression was observed. Physiologic variables and serum propofol and alfentanil concentrations were not significantly altered by esmolol. Although the mechanism remains unclear, significant cortical depression and the onset of burst suppression during a stable, computer-controlled propofol/alfentanil anesthetic was associated with esmolol infusion. IMPLICATIONS: This study demonstrated the suppression of cerebral cortical electrical activity after blinded esmolol infusion during propofol/alfentanil anesthesia. A significant lag was noted between infusion and half-maximal effect (12-16 min). Whether esmolol, a metabolite, or a secondary process was responsible for this cortical suppression remains unknown and requires further study.     

艾司洛尔对老年患者非心脏手术围麻醉期应激反应的抑制作用

目的观察静脉持续输注艾司洛尔对老年患者非心脏手术围麻醉期应激反应的抑制作用。方法65岁以上择期全麻气管插管下行非心脏手术的患者40例，随机分为艾司洛尔组（n=20）与对照组（n=20）。艾司洛尔组麻醉前先静脉注射艾司洛尔0．25mg／kg，然后以20～50μg／（kg·min）的速度用输液泵持续输注，直到气管拔管后5min；对照组以生理盐水替代。记录入室、气管插管前、气管插管后即刻、切皮、手术结束、患者睁眼及拔管后即刻HR、MBP、RPP，以及入室、插管后即刻、切皮、手术结束及拔管后血糖、血香草扁桃酸（BVMA）及血皮质醇水平。结果与对照组比较，艾司洛尔组的HR、RPP在插管后即刻、患者睁眼以及气管拔管后即刻，MBP在气管插管后及睁眼时显著降低（P〈0．05），血糖值在手术结束及拔管后显著降低（P〈0．05或P〈0．01）。艾司洛尔组的芬太尼与异丙酚总量分别为（0．4±0．1）mg和（450．8±98．2）mg，显著少于对照组的（0．5±0．1）mg与（580．3±125．7）mg（P〈0．05）。结论艾司洛尔围麻醉期持续静脉输注可以很好地控制老年患者非心脏手术的应激反应，抑制围麻醉期患者血糖的升高，减少老年患者的麻醉药用量。