Jennifer Lessin

Rocuronium Onset of Action: A Comparison with Atracurium and Vecuronium

The onset, maximal neuromuscular block, and duration of rocuronium were compared with atracurium and vecuronium during enflurane anesthesia. Sixty patients received rocuronium (80,100,120, or 160 μg/kg). Enflurane enhanced a rocuronium neuromuscular block in a dose-related manner; the ED50 was 104 ± 11 and 83 ± 7 μg/kg (SEM) during 1% and 2% enflurane anesthesia, respectively. Patients receiving atracurium (0.12 mg/kg) or vecuronium (0.02 mg/kg) were studied during 1 % enflurane anesthesia until seven in each group qualified by achieving a maximal block between 85% and 97%. These patients were matched with each other and with patients who had received rocuronium. Seven groups of three patients (rocuronium, vecuronium, and atracurium) were obtained. The average difference in maximal block was less than 2% between matched patients. The ratio of dose used to achieve a similar final block suggests potency ratios of 1,8.5, and 1.2 for rocuronium, vecuronium, and atracurium. Rocuroniums onset time (time from drug administration to 50%, 75%, and 90% of final block) was significantly faster than either of the other two muscle relaxants (P < 0.01). Time to 90% of final block was 1.35 min for rocuronium, 3.06 min for atracurium, and 3.71 min for vecuronium. Using these equipotent doses, atracurium also had a shorter time to develop neuromuscular block than vecuronium (P < 0.05). For these three intermediate duration neuromuscular blockers, speed of onset was inversely related to their potency, confirming a relationship that had been demonstrated for the long-acting drugs pancuronium, d-tubocurarine, and gallamine.

The safety and efficacy of oral transmucosal fentanyl citrate for preoperative sedation in young children.

Oral transmucosal fentanyl citrate (OTFC) is a labeled preoperative pediatric sedative.Doses greater than 15 micro g/kg are associated with a high incidence of postoperative nausea and vomiting and occasional respiratory depression. We studied the safety and efficacy of OTFC in children 6 yr old and younger at a dose of 15 micro g/kg. Nineteen patients undergoing surgery associated with postoperative pain were randomized to receive OTFC/intravenous (IV) saline or placebo lozenge/IV fentanyl. After 45 min, patients receiving OTFC became more sedated than the placebo group, but there were no differences in cooperation, apprehension, parental separation, or induction cooperation scores. Preoperatively, neither respiratory depression nor oxygen desaturation occurred. Nine of 10 OTFC patients developed mild pruritus, and three of 10 OTFC patients vomited preoperatively; neither complication occurred in the placebo group. (The high incidence of preoperative vomiting led to the termination of the protocol before the anticipated enrollment of 40 patients.) General anesthesia was induced via a mask, followed by a propofol infusion. SpO2 and respiratory rate were monitored, and sedation, apprehension, cooperation, ease of parental separation, and induction cooperation were scored. One OTFC patient developed rigidity during induction. Emergence and recovery were not delayed by OTFC despite a 50% incidence of postoperative vomiting. We do not recommend the use of OTFC in a 15-micro g/kg dose as a routine preoperative sedative in children 6 yr old and younger. (Anesth Analg 1996;83:1200-5)

High concentration versus incremental induction of anesthesia with sevoflurane in children: A comparison of induction times, vital signs, and complications

STUDY OBJECTIVE To compare sevoflurane induction times and complications in children during a high concentration, primed-circuit method and an incremental induction technique. DESIGN Randomized, prospective open-label study. SETTING Academic university hospital. PATIENTS 40 unpremedicated ASA physical status I and II children age 4 months to 15 years undergoing elective surgical procedures with general anesthesia. INTERVENTIONS Patients were randomized to one of two study groups. In the high concentration group, the anesthesia circuit was primed with 8% sevoflurane in a 2:1 nitrous oxide:oxygen (N2O:O2) mixture. Patients breathed this gas mixture spontaneously until loss of the eyelash reflex. In the incremental group, the face mask was applied and 1% sevoflurane in a 2:1 N2O:O2 mixture was administered. In this group, the sevoflurane concentration was increased by 1% every 2 to 3 breaths. Gas flows of 6 L/min were administered to both groups during the study period. Following loss of the eyelash reflex, the sevoflurane concentration was decreased to 5% until a depth of anesthesia sufficient to start an intravenous catheter was achieved. MEASUREMENTS AND MAIN RESULTS Induction cooperation, induction time (face mask application to loss of the eyelash reflex), one-minute vital signs [blood pressure, heart rate, oxygen saturation via pulse oximetry (SpO2)], induction complications. Induction of anesthesia was faster in the high concentration group than in the incremental group (mean (SD) 42 (9) sec vs. 66 (12) sec, respectively; p < 0.001). Induction complications were minor and occurred with similar frequencies (4/20 patients vs. 3/20 patients). There were no significant intergroup heart rate, blood pressure, or SpO2 differences during induction. No patients required treatment for hypotension or bradycardia. CONCLUSIONS In healthy pediatric patients undergoing mask induction of general anesthesia with sevoflurane, the induction time can be significantly shortened without an increase in the frequency of airway or vital sign complications using a high concentration, primed circuit technique compared with a conventional, incremental induction method.

Sevoflurane versus halothane for general anesthesia in pediatric patients: A comparative study of vital signs, induction, and emergence

STUDY OBJECTIVE To compare vital signs and the speed of induction and emergence with sevoflurane versus halothane in pediatric patients. DESIGN Prospective, randomized, open study. SETTING Thomas Jefferson University Hospital. PATIENTS 40 unpremedicated ASA Physical Status I and II children age 9 months to 16 years undergoing elective inpatient otorhinolaryngologic or orthopedic surgery. INTERVENTIONS Standardized induction of anesthesia with sevoflurane (start: 1%, maximum: 7%) or halothane (start: 0.5%, maximum: 5%) in nitrous oxide/oxygen (N2O/O2). Intubation following vecuronium and 4 minutes of controlled ventilation with 2 minimum alveolar concentration (MAC) drug in O2; 1.5 MAC drug in N2O/O2 delivered for 20 minutes; then 0.75 MAC until the end of surgery. Fentanyl 1 mcg/kg was administered 15 minutes before the anticipated end of surgery, at which time anesthetics were stopped and mechanical ventilation continued until eye opening (emergence). MEASUREMENTS AND MAIN RESULTS Blood pressure, heart rate (HR), oxygen saturation, end-tidal gas concentrations, and temperature were recorded. Induction and emergence times were measured to the nearest second. Induction (loss of eyelash reflex) was faster with sevoflurane (97 +/- 31 sec) than halothane (120 +/- 36 sec; p < 0.05), despite a lower inspired sevoflurane MAC. Emergence was faster with sevoflurane (9.9 +/- 2.9 min vs. 12.5 +/- 4.7 min; p < 0.05), despite a higher MAC multiple of end-tidal sevoflurane concentration at the end of surgery. Following intubation, HR (compared with the preinduction value in the operating room) was significantly higher in the halothane group (136.8% +/- 16.3% vs. 115.0% +/- 25.6%), as was mean arterial pressure (113.2% +/- 25.5% vs. 87.8% +/- 22.6%). This finding corresponded with a higher MAC multiple of end-tidal concentration in the sevoflurane group than in the halothane group. CONCLUSIONS Induction of and emergence from anesthesia was faster with sevoflurane than halothane. Airway complications were low in both groups. Vital signs were more stable with sevoflurane during induction through intubation, and were comparable during maintenance. Sevoflurane is an excellent drug for inhalational induction in pediatric patients.

Intraoperative hemodynamic, renin, and catecholamine responses after prophylactic and intraoperative administration of intravenous enalaprilat.

This study was designed to evaluate effects of enalaprilat, an angiotensin-converting enzyme inhibitor, on hemodynamic and hormonal responses during surgery at endotracheal intubation, incision, and limb-tourniquet inflation. Thirty patients undergoing limb procedures with general anesthesia (N2 O/narcotic technique) and a pneumatic tourniquet were randomized to receive either preoperative enalaprilat (1.25 mg intravenously [IV] 20 min prior to induction) or intraoperative enalaprilat (0.625 mg IV at the onset of tourniquet-associated hypertension), with appropriate placebo controls. Arterial blood pressure and heart rate increased significantly in response to intubation in the placebo group. Although there were no significant differences in catecholamine levels, plasma renin activity was significantly increased at postincision in the preoperative-enalaprilat group versus the placebo group. This suggests that activation of the renin-angiotensin system may play a key role in mediation of intraoperative hemodynamic responses to endotracheal intubation. With respect to tourniquet hypertension, preoperative or intraoperative treatment with enalaprilat reduced neither the pressor response to tourniquet inflation nor the amount of enflurane subsequently required to control arterial blood pressure. These findings suggest that this response is mediated by pain pathways, and may be treated more effectively with anesthesia/analgesia. (Anesth Analg 1995;80:583-90)

A comparison of desflurane and isoflurane in prolonged surgery

STUDY OBJECTIVE To compare desflurane with isoflurane in several anesthetic situations. DESIGN Intubating conditions, hemodynamic response to intubation, maintenance hemodynamics, and speed of recovery from desflurane and isoflurane anesthesia were evaluated. In addition, interaction with a muscle relaxant at low and high concentrations of the anesthetics were compared. SETTING Thomas Jefferson University Hospital. PATIENTS Thirty-two patients who received general anesthesia for lengthy, mostly orthopedic procedures. INTERVENTIONS Immediately after induction with thiopental sodium, desflurane or isoflurane in nitrous oxide-oxygen was administered via face mask. Anesthesia was deepened until end-tidal concentration reached 1.7 minimum alveolar concentration (MAC). The trachea was intubated without the aid of a muscle relaxant. Heart rate (HR) and blood pressure (BP) were recorded before and at 1, 2, 4, 5, and 10 minutes after intubation. Noninvasive cardiac output (CO) and systemic vascular resistance (SVR) were determined while the patient was awake, immediately before intubation, and at 5 and 10 minutes after intubation. Following intubation, the concentration of desflurane or isoflurane was lowered until the end-tidal concentration reached 0.65 MAC (low-MAC group), 1.25 MAC (high-MAC group), or 0 MAC (control group). Pancuronium bromide in 0.005 mg/kg doses was administered incrementally until T1 (first twitch of train-of-four) was depressed more than 90%. ED50 and ED95 for pancuronium with balanced anesthesia and for desflurane or isoflurane in low and high MACs, as well as speed of recovery, were determined. The time to responsiveness and awakening also was determined. MEASUREMENTS AND MAIN RESULTS There was no significant difference between desflurane and isoflurane in intubating conditions or in BP or HR response to tracheal intubation. Both anesthetics increased HR significantly during induction. BP rose with desflurane at the preintubation point; other points showed no difference. A hyperdynamic response of increased HR and BP above 20% of baseline values was seen more frequently with desflurane (n = 7) than with isoflurane (n = 1). CO was elevated at all times after induction for low and high concentrations of both drugs, while SVR decreased over the same time with no significant difference between drugs. ED50 and ED95 for pancuronium were similar under desflurane and isoflurane at both low and high MAC, but they were significantly lower than under balanced anesthesia. Awakening times were similar for desflurane and isoflurane. CONCLUSIONS Desflurane is similar to isoflurane in providing anesthesia for intubation and maintenance. Desflurane tends to increase HR and occasionally causes a hyperdynamic response during rapid deepening of anesthesia. It is very similar to isoflurane in its interaction with pancuronium.

Evaluation of an investigational wearable injector in healthy human volunteers

ABSTRACT Objectives: Introduction of a wearable device for subcutaneous delivery of larger volume bolus injections would encourage patient compliance and reduce the burden on healthcare services. With one such wearable device commercially available, this study examined the safety and functionality of an investigational device in volunteers. Methods: Four devices were applied to the subject’s abdomen: 1) Investigational Device, 2) Investigational Device: subject movement, 3) Control Device: FDA-cleared syringe driver with FDA-cleared infusion set, 4) Control Device: FDA-cleared syringe driver attached to investigational device. Three milliliters of saline were infused through the four devices over 3 minutes. Results: 84 devices were applied to 21 subjects. Three milliliters of saline were safely delivered subcutaneously from the investigational and control devices. Two control devices had occlusions and in each case the pump reached its high pressure limit of 12 psi. VAS pain measurements showed minimal pain for all subjects. Pain scores were significantly (p < 0.001) higher than baseline at the end of injection: mean pain level ranged from 2.0–22.0 mm. Conclusions: The investigational device performed as intended with minimal pain during needle insertion and infusion, and no leaking of fluid at the skin puncture site. Two occlusions occurred with the control devices.