Kevin W. Klein

Sugammadex Reversal of Rocuronium-induced Neuromuscular Blockade: A Comparison with Neostigmine–glycopyrrolate and Edrophonium–atropine

BACKGROUND:Sugammadex is a modified γ cyclodextrin compound, which encapsulates rocuronium to provide for a rapid reversal of residual neuromuscular blockade. We tested the hypothesis that sugammadex would provide for a more rapid reversal of a moderately profound residual rocuronium-induced blockade than the commonly used cholinesterase inhibitors, edrophonium and neostigmine. METHODS:Sixty patients undergoing elective surgery procedures with a standardized desflurane–remifentanil–rocuronium anesthetic technique received either sugammadex, 4 mg/kg IV (n = 20), edrophonium, 1 mg/kg IV and atropine, 10 μg/kg IV (n = 20), or neostigmine, 70 μg/kg IV and glycopyrrolate, 14 μg/kg IV (n = 20) for reversal of neuromuscular blockade at 15 min or longer after the last dose of rocuronium using acceleromyography to record the train-of-four (TOF) responses. Mean arterial blood pressure and heart rate values were recorded immediately before and for 30 min after reversal drug administration. Side effects were noted at discharge from the postanesthesia care unit. RESULTS:The three groups were similar with respect to their demographic characteristics and total dosages of rocuronium prior to administering the study medication. Although the initial twitch heights (T1) at the time of reversal were similar in all three groups, the time to achieve TOF ratios of 0.7 and 0.9 were significantly shorter with sugammadex (71 ± 25 and 107 ± 61 s) than edrophonium (202 ± 171 and 331 ± 27 s) or neostigmine (625 ± 341 and 1044 ± 590 s). All patients in the sugammadex group achieved a TOF ratio of 0.9 ≤5 min after reversal administration compared with none and 5% in the edrophonium and neostigmine groups, respectively. Heart rate values at 2 and 5 min after reversal were significantly higher in the neostigmine-glycopyrrolate group compared with that in sugammadex. Finally, the incidence of dry mouth was significantly reduced in the sugammadex group (5% vs 85% and 95% in the neostigmine and edrophonium groups, respectively). CONCLUSION:Sugammadex, 4 mg/kg IV, more rapidly and effectively reversed residual neuromuscular blockade when compared with neostigmine (70 μg/kg IV) and edrophonium (1 mg/kg IV). Use of sugammadex was associated with less frequent dry mouth than that with the currently used reversal drug combinations.

The effect of timing of ondansetron administration in outpatients undergoing otolaryngologic surgery

A randomized, double-blind, placebo-controlled study was designed to compare the relative efficacy of prophylactic ondansetron, 4 mg intravenously (IV), when administered before induction of anesthesia or at the end of surgery to an outpatient population at high risk of developing postoperative nausea and vomiting (PONV). Patients undergoing otolaryngologic surgery were randomly assigned to one of three different treatment groups: Group I (placebo) received saline 5 mL prior to induction of anesthesia and again at the end of surgery; Group II received ondansetron 4 mg in 5 mL prior to induction of anesthesia and saline 5 mL at the end of surgery; and Group III received saline 5 mL prior to induction of anesthesia and ondansetron 4 mg at the end of surgery. All patients received the same general anesthetic technique. A standardized regimen of rescue antiemetics was administered in the recovery room to patients with >or=to2 emetic episodes or at the patients request for persistent nausea. Episodes of nausea and vomiting, as well as the need for rescue antiemetics, were recorded for 24 h after the operation. The incidences of nausea and emesis in the recovery room after prophylactic ondansetron, 4 mg IV, administered either before induction (68% and 20%, respectively) or at the end of surgery (60% and 4%, respectively) were not significantly decreased compared to the placebo control group (80% and 12%, respectively). However, when ondansetron was administered at the end of the operation, it significantly reduced the need for rescue antiemetics in the recovery room (36% vs 64% in the control group). The postanesthesia care unit and hospital discharge times were similar in all three study groups. One patient in Group II and one patient in Group III were hospitalized because of intractable symptoms related to PONV. After discharge from the ambulatory surgery unit, the incidence of nausea, vomiting, and the need for rescue antiemetic drugs were similar in all three treatment groups. In conclusion, ondansetron (4 mg IV) was more effective in reducing the need for rescue antiemetics in the recovery room when administered at the end versus prior to the start of otolaryngologic surgery. Therefore, when ondansetron is used for antiemetic prophylaxis in outpatients undergoing otolaryngologic procedures, it should be administered at the end of the operation rather than prior to induction of anesthesia. (Anesth Analg 1997;84:331-6)

The Efficacy of Premedication with Celecoxib and Acetaminophen in Preventing Pain After Otolaryngologic Surgery

Non-opioid analgesics are often used to supplement opioids for the management of perioperative pain. In this randomized, double-blinded, placebo-controlled study, we examined the effects of acetaminophen and a cyclooxygenase type-2 inhibitor, celecoxib, when administered alone or in combination, before elective otolaryngologic surgery in 112 healthy outpatients. Subjects were assigned to 1 of 4 study groups: Group 1, placebo (vitamin C, 500 mg per os [PO]); Group 2, acetaminophen 2000 mg PO; Group 3, celecoxib 200 mg PO; or Group 4, acetaminophen 2000 mg and celecoxib 200 mg PO. All patients received a standardized anesthetic technique. During the postoperative period, pain was assessed using a 10-point verbal rating scale. Recovery times, the need for rescue analgesics, side effects, and patient satisfaction scores were also recorded. The combination of acetaminophen and celecoxib was significantly more effective than placebo in reducing postoperative pain. Celecoxib, when administered alone or in combination with acetaminophen, improved patients’ satisfaction with their postoperative analgesia. With the combination of acetaminophen and celecoxib, an additional expenditure of

Autonomic Reflex Dysfunction in Patients Presenting for Elective Surgery Is Associated with Hypotension after Anesthesia Induction

6.16 would be required to obtain complete satisfaction with postoperative pain management in one additional patient who would not have been completely satisfied if he/she had received the placebo. However, oral celecoxib or acetaminophen alone was not significantly more effective than placebo in reducing postoperative pain when administered before surgery. We conclude that oral premedication with a combination of acetaminophen (2000 mg) and celecoxib (200 mg) was highly effective in decreasing pain and improving patient satisfaction after outpatient surgery.

Effect of low-dose droperidol on the QT interval during and after general anesthesia: a placebo-controlled study.

BackgroundAutonomic reflex dysfunction in patients with diabetes is associated with an increased incidence of hypotension after induction of anesthesia. Whether this finding can be extrapolated to patients with autonomic dysfunction from other causes (e.g., advanced age, hypertension, altered ventricular function) has not been established. MethodsThe authors investigated whether autonomic reflex dysfunction in a more generalized patient group (26 consecutively consenting day-surgery patients older than 39 yr) was similarly associated with the occurrence of hypotension after induction. Preoperatlve tests of autonomic function included: Valsalva maneuver, change in heart rate with forced breathing, change in heart rate and blood pressure with standing, and spectral analysis of heart rate variability. Anesthesia was induced with 3–5 mg/kg thiopental, 2 μg/kg fentanyl, and 60% N2O; 0.1 mg/kg vecuronium was used for paralysis; 0–1.5% isoflurane was added for maintenance of anesthesia after intubation. Noninvasive measurements of mean blood pressure were obtained every minute for 10 min after induction and then every 3 min until skin incision. ResultsTwelve patients developed hypotension (mean blood pressure < 70 mmHg), and 14 patients did not. Measurements of autonomic reflex function were significantly more abnormal in the patients who developed hypotension (P < 0.006 for Valsalva measurements, heart rate variability parameters, and change in heart rate with forced breathing). Using critical test values for autonomic tests, the incidence of hypotension was 67–83% in patients with autonomic nervous system dysfunction versus 9–17% in other patients. ConclusionsThe results document that: (1) some degree of autonomic reflex dysfunction is not uncommon in patients older than 39 yr presenting for elective surgery, and (2) such dysfunction is associated with an increased incidence of hypotension when using the described induction technique.

The effect of pregabalin on preoperative anxiety and sedation levels: a dose-ranging study.

BACKGROUND Since the effects of antiemetic doses of droperidol on the QT interval have not been previously studied, the authors designed a randomized, double-blind, placebo-controlled study to evaluate the intraoperative and postoperative effects of small-dose droperidol (0.625 and 1.25 mg intravenous) on the QT interval when used for antiemetic prophylaxis during general anesthesia. METHODS One hundred twenty outpatients undergoing otolaryngologic procedures with a standardized general anesthetic technique were enrolled in this study. After anesthetic induction and before the surgical incision, 60 patients were given either saline or 0.625 or 1.25 mg intravenous droperidol in a total volume of 2 ml. A standard electrocardiographic lead II was recorded immediately before and every minute after the injection of the study medication during a 10-min observation period. The QTc (QT interval corrected for heart rate) was evaluated from the recorded electrocardiographic strips. In 60 additional patients, a 12-lead electrocardiogram was obtained before and at specific intervals up to 2 h after surgery to assess the effects of droperidol and general anesthesia on the QTc. Any abnormal heartbeats or arrhythmias during the operation or the subsequent 2-h monitoring interval were also noted. RESULTS Intravenous droperidol, 0.625 and 1.25 mg, prolonged the QT interval by an average of 15 +/- 40 and 22 +/- 41 ms, respectively, at 3-6 min after administration during general anesthesia, but these changes did not differ significantly from that seen with saline (12 +/- 35 ms) (all values mean +/- SD). There were no statistically significant differences among the three study groups in the number of patients with greater than 10% prolongation in QTc (vs. baseline). Although general anesthesia was associated with a 14- to 16-ms prolongation of the QTc interval in the early postoperative period, there was no evidence of droperidol-induced QTc prolongation after surgery. Finally, there were no ectopic heartbeats observed on any of the electrocardiographic rhythm strips or 12-lead recordings during the perioperative period. CONCLUSION Use of a small dose of droperidol (0.625-1.25 mg intravenous) for antiemetic prophylaxis during general anesthesia was not associated with a statistically significant increase in the QTc interval compared with saline. More importantly, there was no evidence of any droperidol-induced QTc prolongation immediately after surgery.

The efficacy of celecoxib premedication on postoperative pain and recovery times after ambulatory surgery: A dose-ranging study

BACKGROUND: Pregabalin is a gabapentinoid compound, which has been alleged to possess anxiolytic, analgesic, and anticonvulsant properties. We hypothesized that premedication with oral pregabalin would produce dose-related reductions in acute (state) anxiety and increases in sedation (sleepiness) before induction of general anesthesia. A secondary objective was to determine if premedication with pregabalin would reduce postoperative pain. METHODS: One hundred eight ASA I–III outpatients undergoing elective surgery were randomly assigned to one of the four premedication treatment groups: 1) control group received placebo capsules, 2) pregabalin 75 group received pregabalin 75 mg, po, 3) pregabalin 150 group received pregabalin 150 mg, po, and 4) pregabalin 300 group received pregabalin 300 mg, po. The effects of the study drug on the patients’ level of anxiety, sedation, and pain were assessed at baseline (immediately before study drug administration), at 30 and 60 min after drug administration, and immediately before induction of anesthesia, as well as at 30-min intervals in the postanesthesia care unit (PACU) using standardized 11-point verbal rating scales, with 0 = none to 10 = maximal effect. The need for postoperative opioid analgesic medication, incidence of nausea and vomiting, requirement for rescue antiemetics, and times to discharge from the PACU and hospital, as well as the patients’ quality of recovery scores, and late recovery outcomes (e.g., resumption of dietary intake and recovery of bowel function) were assessed at a 7-day follow-up interview. RESULTS: Demographic characteristics, times between study drug administration to anesthetic induction, type of surgical procedures, duration of anesthesia, PACU and hospital discharge time, as well as the requirement for fentanyl in the PACU, did not differ among the four study groups. Anxiety levels remained unchanged during the preoperative evaluation period, and did not differ among the four study groups. Sedation scores were significantly higher in the pregabalin 300 group at the preinduction assessment interval and at 90 and 120 min after surgery compared with the control group (5 ± 3 vs 3 ± 2, 7 ± 4 vs 5 ± 3, 8 ± 4 vs 4 ± 4, respectively, P < 0.05). CONCLUSION: Preoperative pregabalin administration (75–300 mg po) increased perioperative sedation in a dose-related fashion, but failed to reduce preoperative state anxiety, postoperative pain, or to improve the recovery process after minor elective surgery procedures.

A comparison of the costs and efficacy of ondansetron versus dolasetron for antiemetic prophylaxis

Recently, the Food and Drug Administration increased the celecoxib dosage recommendation from 200 mg to 400 mg for acute pain management. No studies have directly compared the analgesic efficacy of different doses of celecoxib for the prevention of postoperative pain. In this prospective, double-blinded, placebo-controlled study, we compared oral celecoxib 200 mg to 400 mg when administered for premedication of outpatients undergoing minor ear-nose-throat surgery. A total of 93 healthy outpatients were assigned to 1 of 3 study groups: control (placebo; n = 30), celecoxib 200 mg (n = 30), or celecoxib 400 mg (n = 33). The study drug was given orally 30–45 min before surgery, and all patients received a standardized general anesthetic technique. During the postoperative period, pain scores (0–10), recovery times, the need for rescue analgesics, quality of recovery (0–100), patient satisfaction with pain management (0–100), and side effects were recorded. Pain was assessed at 30-min intervals using a verbal rating scale, with 0 = no pain to 10 = worst pain imaginable, in the postanesthesia care unit and day surgery unit recovery areas and at 24 h after surgery. Celecoxib 400 mg was significantly more effective than 200 mg (and placebo) in reducing postoperative pain. Both celecoxib 200 mg and 400 mg were more effective than placebo in reducing the postoperative fentanyl requirement (74 ± 67 &mgr;g and 56 ± 62 &mgr;g versus 120 ± 86 &mgr;g, respectively). The larger dose of celecoxib significantly reduced the percentage of patients with severe pain at discharge (6% versus 37% and 30% in the celecoxib 200 mg and control groups, respectively). The median number of doses of oral analgesic medication after discharge was also significantly reduced in the celecoxib 400 mg group (0 versus 2 and 2 in the celecoxib 200 mg and control groups, respectively). However, no differences were found among the three study groups with respect to recovery times and secondary outcome variables (e.g., patient satisfaction and quality of recovery). We conclude that oral premedication with celecoxib 400 mg was more effective than 200 mg in reducing severe postoperative pain and the need for rescue analgesic medication in the postoperative period. IMPLICATIONS: Oral premedication with celecoxib 400 mg was more effective than 200 mg in reducing postoperative pain and the need for rescue analgesic medication in the early postoperative period. However, neither dose of celecoxib was more effective than a placebo in facilitating the recovery process after outpatient surgery.

Cost-efficacy of Rofecoxib versus Acetaminophen for Preventing Pain after Ambulatory Surgery

The optimal dose and timing of 5-HT3 antagonist administration for prophylaxis against postoperative nausea and vomiting (PONV) remains controversial. Although 5-HT3 antagonists seem to be most effective when administered near the end of surgery, there are no data on the comparative efficacy or costs associated with the 5-HT3 antagonists dolasetron and ondansetron when administered at the end of the operation. In this double-blinded study, 200 outpatients undergoing otolaryngologic procedures with a standardized general anesthetic received 4 (O4) or 8 mg (O8) of ondansetron or 12.5 (D12.5) or 25 mg (D25) of dolasetron IV within 30 min before the end of surgery. A blinded observer recorded the emetic episodes, maximum nausea score, recovery room resource and drug use, nursing time spent managing PONV, times to achieve discharge criteria from the Phase 1 and 2 recovery units, postdischarge emesis, and patient satisfaction. Total costs were calculated by using the perspective of a free-standing surgicenter. There were no differences in patient demographics, incidence of PONV, need for rescue medications, time spent in the recovery areas, unanticipated hospital admissions, or patient satisfaction among the four treatment groups. The mean total costs (95% confidence intervals) to prevent PONV in one patient were lowest in the D12.5 group:

Transdermal scopolamine for the reduction of postoperative nausea in outpatient ear surgery : a double-blind, randomized study

23.89 (17.18–28.79) vs