High frequency current catheter ablation of accessory conduction pathways

Postoperative nausea and vomiting (PONV) are relatively common troublesome distressing symptoms. The incidence is reported to be as high as 20-51%. Ninety adult ASA I and II patients scheduled for laparoscopic gynecological or surgical interventions, were randomly and equally assigned to one of the three groups in the immediate postoperative period: Group 1 received 0.1 ml.kg(-1) normal saline intravenously, while Group 2 received 0.5 mg.kg(-1) ephedrine intramuscularly and Group 3 received 0.25 mg.kg(-1) propofol intravenously as preventive antiemetic therapy. Sixty-six, 33 and 50 percent of patients experienced nausea and vomiting syndrome in Group 1, 2 and 3 respectively. Both ephedrine and propofol proved to have antiemetic properties. Ephedrine treated group of patient had significant less emetic score than propofol. No significant hemodynamic changes were recorded in both groups.     

Expression of LECAM-1 and LFA-1 on pre-B lymphoma cells but not on preneoplastic pre-B cells in SL/KH mice

BACKGROUND AND OBJECTIVES: The efficacy of operatively administered spinal neostigmine to provide analgesia and that of different antiemetics to prevent neostigmine-related nausea and vomiting were evaluated in patients undergoing tibial or ankle reconstruction. METHODS: One hundred patients were randomized to five groups (n = 20). The intravenous antiemetic test drug (except propofol) was given as premedication in the holding room, after intravenous midazolam, 0.05 mg/kg. The subarachnoid drugs administered were 20 mg bupivacaine (0.5%) in conjunction with 100 micrograms neostigmine, except for the saline group (S group), which received bupivacaine and saline. The S group, the neostigmine group (N group), and the propofol group (P group) received saline as the intravenous test drug. The droperidol group (D group) received intravenous droperidol 0.5 mg, and the metoclopramide group (M group) received intravenous metoclopramide 10 mg. The P group had a continuous intravenous propofol infusion (2-4 mg/kg/hr), started 10 minutes after the spinal injection. Nausea, emetic episodes, and the need for analgesic (disclofenac) or antiemetic medication were recorded for the first 24 hours following surgery and scored by a 10-cm visual analog scale (VAS). RESULTS: Subarachnoid neostigmine 100 micrograms did not affect subarachnoid bupivacaine analgesia as measured by time to first rescue analgesic in most patients, but it decreased the overall 24-hour visual analog scale (VAS) scores and the need for postoperative analgesics in 24 hours (P < .001). The incidence of intraoperative nausea and vomiting was higher in the N, D, and M groups than in the S group (P < .001). Following surgery, the 3-hour VAS assessment for emesis was higher for the N, P, and M groups than for the S group (P < .05). The overall 24-hour assessment was similar among groups. CONCLUSIONS: Subarachnoid neostigmine reduced postoperative pain scores and analgesic requirements. Whether it prolonged the duration of action of diclofenac or enhanced the mechanisms involved in spinal analgesia cannot be determined from these data. Although propofol and droperidol appeared to be more effective during and after surgery, respectively, all neostigmine groups were associated with a high consumption of antiemetics.     

The effect of blockade of the AMPA/kainate receptors of the nucleus accumbens on synaptic dopamine release during an emotional conditioned response

We studied the effect of combining prophylactic ondansetron (4 mg intravenously [IV]) to desflurane-based anesthesia in 90 ASA grade I or 11 women undergoing outpatient gynecological laparoscopy. Recovery after anesthesia, with special focus on postoperative nausea and vomiting (PONV), was assessed. Control groups received a similar desflurane anesthetic (placebo) or a propofol-infusion-based (active control) anesthetic. The study design was randomized, controlled, and double-blind (regarding ondansetron) and single-blind (regarding the anesthetic technique). Early recovery (eye opening, orientation, following commands, sitting) was similar in the three groups. However, overall home readiness (toleration of oral fluids, walking, pain tolerable by oral analgesics, no or only mild nausea) was achieved faster in the desflurane group receiving ondansetron (109 [21-937] min, P < 0.01) and in the propofol group (110 [33-642] min, P < 0.001) when compared to the desflurane only group (372 [45-723] min) (median [range]). The total incidence of PONV in the desflurane-only group was 80% (P < 0.01), compared to 40% and 20% in the desflurane group receiving ondansetron and the propofol group, respectively. The postoperative antiemetic requirements were consistently and significantly (P < 0.01) higher in the desflurane-only group compared to the other two groups. Postoperative sedation, analgesic requirements, and psychomotor recovery (assessed by the Maddox Wing and the Digit Symbol Substitution Tests) were similar in the three groups. Our results suggest that in order to achieve a propofol-like recovery profile in patients with a high likelihood of PONV, desflurane should be combined with a potent antiemetic (e.g., ondansetron).     

Determination of plasma concentrations of propofol associated with 50% reduction in postoperative nausea

BACKGROUND: Subhypnotic doses of propofol possess direct antiemetic properties. The authors sought to determine the plasma concentration of propofol needed to effectively manage postoperative nausea and vomiting. METHODS: Patients aged 18-70 yr who were classified as American Society of Anesthesiologists physical status 1 or 2 and had surgery during general anesthesia were approached for the study. Only patients who had nausea (verbal rating score > 5 on a 0- to 10-point scale), retching, or vomiting in the postanesthetic care unit participated. Propofol was administered to these patients to achieve target plasma concentrations of 100, 200, 400, and 800 ng/ml using a computer-assisted continuous infusion device. Target concentrations were increased every 15 min until patients described at least a 50% reduction in symptoms on the verbal rating score. An arterial blood sample was obtained at each step. The measured plasma propofol concentrations were used to analyze data. Blood pressure, heart and respiratory rates, arterial blood saturation, sedation score, and overall satisfaction with treatment were recorded. RESULTS: Of the 89 patients who consented to the study, 15 patients met entry criteria and were enrolled. Five of these patients also had retching or vomiting when they entered the study. Fourteen patients responded successfully to treatment. One patient did not achieve the required response at plasma concentrations of 830 ng/ml. Hence the success rate for the treatment of postoperative nausea and vomiting was 93%. Among patients who responded, the median plasma concentration associated with an antiemetic response was 343 ng/ml. There was no difference in sedation scores from baseline and no episodes of desaturation. Hemodynamic parameters were stable during the study. CONCLUSIONS: Propofol is generally efficacious in treating postoperative nausea and vomiting at plasma concentrations that do not produce increased sedation. Simulations indicate that to achieve antiemetic plasma propofol concentrations of 343 ng/ml, a bolus dose of 10 mg followed by an infusion of approximately 10 microg x kg(-1) x min(-1) are necessary.     

Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate

BACKGROUND: A naloxone infusion is effective in reducing epidural and intrathecal opioid-related side effects. The use of naloxone infusion concomitant with intravenous morphine patient-controlled analgesia (PCA) has not been evaluated, probably because of an expected direct antagonism of the systemic opioid effect. The authors compared the incidence of morphine-related side effects and the quality of analgesia from two small doses of naloxone infusion. METHODS: Sixty patients classified as American Society of Anesthesiologists physical status 1, 2, or 3 who were scheduled for total abdominal hysterectomies were enrolled in the study. Patients received a standardized general anesthetic. In the postanesthetic care unit, patients received morphine as a PCA. They were randomized to receive either 0.25 microg x kg(-1) x h(-1) naloxone (low dose), 1 microg x kg(-1) x h(-1) (high dose), or saline (placebo) as a continuous infusion. Verbal rating scores for pain, nausea, vomiting, and pruritus; sedation scores; requests for antiemetic; and morphine use were recorded for 24 h. Blood pressure, respiratory rate, and oxyhemoglobin saturation were also monitored. RESULTS: Sixty patients completed the study. Both naloxone doses were equally effective in reducing the incidence of nausea, vomiting, and pruritus compared with placebo (P < 0.05 by the chi-squared test). There was no difference in the verbal rating scores for pain between the groups. The cumulative morphine use was the lowest in the low-dose group (42.3 +/- 24.1 mg; means +/- SD) compared with the placebo (59.1 +/- 27.4 mg) and high-dose groups (64.7 +/- 33.0 mg) at 24 h (P < 0.05 by analysis of variance). There was no incidence of respiratory depression (<8 breaths/min) and no difference in sedation scores, antiemetic use, respiratory rate, and hemodynamic parameters among the groups. CONCLUSIONS: Naloxone is effective in preventing PCA opioid-related side effects. Naloxone infusion at 0.25 microg x kg(-1) x h(-1) not only attenuates these side effects but appears to reduce postoperative (beyond 4-8 h) opioid requirements. This dosing regimen can be prepared with 400 microg naloxone in 1,000 ml crystalloid given in 24 h to a patient weighing 70 kg.     

Randomised double-blind clinical trial of intermediate- versus high-dose chloral hydrate for neuroimaging of children

Orally administered chloral hydrate is the most widely used sedative in children undergoing MRI. We compared intermediate- and high-dose oral chloral hydrate in 97 consecutive children undergoing MRI in a prospective, controlled, double-blind, randomised clinical trial. There were 50 girls and 47 boys, mean weight (+/- SD) 14.7 +/- 6.4 kg, and mean age 38 +/- 31. The children were randomly allocated to receive chloral hydrate syrup either 70 mg/kg (group A, n = 50) or 100 mg/kg (group B, n = 47). These two groups were not significantly different in sex, weight, age, diagnosis or ambulatory medication. The mean initial dose (+/- SEM) was 64 +/- 2 mg/kg for group A and 93 +/- 2 mg/kg for group B. Because adequate sedation was not achieved, 14 patients in group A and 6 in group B required a second dose, giving a mean total dose of 70 +/- 2 mg/kg for group A and 96 +/- 2 mg/kg for group B. The percentage of successful examinations after the initial dose (A: 64%, B: 87%; p < 0.05) and the total dose (A: 92%, B:100%; p = 0.14) was higher in group B. Significant differences were found for the time of onset of sedation (A:28 +/- 2 min, B: 21 +/- 1 min; p < 0.05), but not for the time to spontaneous awakening after the completion of the examination. The rate of adverse reactions was similar (A: 20%, B: 21%; p = 1.00). We conclude that high-dose oral chloral hydrate improves the management of children undergoing MRI.     

Relationship between auditory intensity discrimination in noise and olivocochlear efferent system activity in humans

The intravenous (i.v.) steroid anesthetic, eltanolone, compares favorably to propofol with respect to its induction characteristics. This double-blind investigation was designed to compare the induction and recovery profile of eltanolone (versus propofol) when it was used for both induction and maintenance of ambulatory anesthesia. Eighty-three consenting ASA physical status I-III outpatients undergoing minor gynecologic or urologic procedures lasting 10-40 min were randomly assigned to one of three anesthetic treatment groups. All patients received midazolam, 2 mg i.v., and fentanyl, 50 micrograms i.v., before induction of anesthesia. The control group (Group 1) was induced with propofol, 2.4 mg/kg i.v. (18-60 yr or ASA physical status I or II) or 1.6 mg/kg i.v. (61-80 yr and/or ASA physical status III), followed by intermittent bolus doses of 0.6 mg/kg i.v. in combination with N2O 67% for maintenance of anesthesia. In Group 2, anesthesia was induced with eltanolone, 0.75 mg/kg i.v., (18-60 yr and/or ASA physical status I or II) or 0.5 mg/kg i.v. (61-80 yr and/or ASA physical status III), and maintained with intermittent bolus injections of 0.2 mg/kg i.v. and N2O 67%. Group 3 received eltanolone, 1.0 mg/kg i.v. (18-60 yr and/or ASA physical status I or II), or 0.75 mg/kg i.v. (61-80 yr and/or ASA physical status III), followed by intermittent bolus injections of 0.2 mg/kg i.v. and N2O 67%. In addition to recording the induction and recovery times and side effects, psychomotor testing was performed before and at 30-min intervals after anesthesia. Induction times (57 +/- 23, 67 +/- 26, and 61 +/- 22s, respectively) were similar in all three groups. Although eltanolone produced no pain on injection (versus 52% in the propofol group), 10% of the eltanolone-treated patients (versus none in the propofol group) developed transient cutaneous (rash-like) reactions. The total dose of study medication used during the anesthetic period was 9.2 +/- 3.7 mg.kg-1.h-1 in the propofol group compared with 3.3 +/- 1.4 mg.kg-1.h-1 and 3.3 +/- 1.9 mg.kg-1.h-1 in Groups 2 and 3, respectively. Early recovery times were significantly shorter after propofol anesthesia. However, times to ambulation, micturition, and being judged "fit for discharge," as well as recovery of cognitive function, were similar in all three groups. Although ethanolone seems to be a safe and effective i.v. anesthetic, these data suggest that it is unlikely to replace propofol in the ambulatory setting. Implications: Eltanolone is an investigational steroid anesthetic that causes less pain on injection and less cardiovascular depression than propofol (the most widely used intravenous anesthetic in the outpatient setting). Unfortunately, emergence from anesthesia after ambulatory surgery is slower with eltanolone compared with propofol. Therefore, it is unlikely that eltanolone will replace propofol for outpatient anesthesia.     

Modified oral ondansetron regimen for cyclophosphamide-induced emesis in lupus nephritis

OBJECTIVE: To evaluate the antiemetic efficacy of a modified regimen of oral ondansetron and dexamethasone in patients with lupus nephritis undergoing treatment with cyclophosphamide whose conventional antiemetic regimen had failed. DESIGN: A before-after prospective observational pilot project. SETTING: A federal research hospital. PATIENTS: Fourteen outpatients with lupus nephritis receiving intravenous cyclophosphamide 0.75-1.0 g/m2 had previously experienced chemotherapy-induced emetic events (vomiting or retching) while receiving a standard combination intravenous antiemetic regimen. The regimen consisted of four doses of thiethylperazine 10 mg and diphenhydramine 25 mg every 6 hours, and two doses of lorazepam 0.5 mg every 6 hours starting at 1 hour prior to cyclophosphamide. A subset of 8 patients previously completed a blinded study in which they received the intravenous formulation of ondansetron (4 doses of 4-16 mg q4h) administered orally beginning 30 minutes prior to the cyclophosphamide infusion. MAIN OUTCOME MEASURES: The number of emetic events and cost of drug administration were assessed for the modified ondansetron intervention and compared with those of the standard antiemetic regimen. The incidence of emetic events and visual analog nausea scores for the subset of eight patients were also evaluated. INTERVENTIONS: To account for the delayed onset of emesis associated with cyclophosphamide, patients received both ondansetron 8 mg orally every 4 hours (3 doses) and dexamethasone 10 mg orally (1 dose) beginning 4 hours after the cyclophosphamide infusion. This is different from the manufacturer's recommended dose schedule, in which ondansetron is administered prior to chemotherapy. RESULTS: No emetic events were observed following the administration of oral ondansetron/dexamethasone. The 95% confidence interval for the true rate of emesis was 0% to 19.3%. There was a significant difference in efficacy between ondansetron/dexamethasone and the triple antiemetic regimen (p < 0.0002). None of the patients experienced adverse effects while receiving the ondansetron/dexamethasone regimen. Cost comparisons (including admixture and nursing administration times) for standard combination therapy and oral ondansetron/dexamethasone were $109.09 and $70.24, respectively. No difference in emetic events or nausea ratings was observed between oral ondansetron/dexamethasone tablets and oral administration of ondansetron using the intravenous formula. CONCLUSIONS: This study suggests that a modified oral ondansetron/dexamethasone regimen is safe and efficacious, and costs less than alternative regimens to prevent cyclophosphamide-induced emesis in patients with lupus nephritis.     

Comparison of propofol and methohexital continuous infusion techniques for conscious sedation

PURPOSE: Methohexital and propofol have been shown to be effective agents for continuous intravenous infusion to produce conscious sedation during oral surgical procedures. The current study was conducted to compare these techniques for intraoperative cardiopulmonary stability, patient cooperation, amnesia, comfort, recovery time, and postoperative nausea and vomiting. METHODS: Seventy ASA Class I or Class II patients between the ages of 18 and 40 years, scheduled for surgical extraction of impacted third molars, were entered into the study. Thirty-five patients were assigned to group A (methohexital) and 35 were assigned to group B (propofol). Intravenous sedation was accomplished using premedication with 1.5 microg/kg of fentanyl and 0.05 mg/kg of midazolam followed by the continuous infusion of methohexital or propofol at a rate of 50 microg/kg/min. The infusion was then titrated to 100 microg/kg/min to accomplish a level of sedation in which the eyes were closed and the patients were responsive to verbal commands. Subjects were monitored for variability of heart rate, blood pressure, oxygen saturation, amnesia, comfort, cooperation, nausea and vomiting, and recovery time based on cognitive, perceptual, and psychomotor tests. RESULTS: There was no statistical difference between the two medication groups except for heart rate, which was found to increase by 11 beats/min for group A and only three beats/min in group B. CONCLUSION: A continuous infusion technique using either methohexital or propofol (50 to 100 microg/kg/min) was found to be safe and effective, with no clinically significant differences in cooperation, cardiopulmonary stability, recovery time, amnesia, comfort, and the incidence of nausea or vomiting. However, the cost-effectiveness of methohexital is superior to that of propofol.     

Study on clinical effect of a continuous intravenous infusion of azasetron against nausea and vomiting induced by anticancer drugs including CDDP

Azasetron, a selective 5-HT3 receptor antagonist, has been previously shown to be highly effective in the prophylaxis of nausea and vomiting induced by anticancer drugs and is widely used in the clinical setting in Japan. In order to improve the antiemetic effect of azasetron, we designed a continuous intravenous infusion method of this drug and compared the antiemetic effect of this method with that of standard bolus intravenous injection on nausea and vomiting associated with anticancer drugs including 75 mg/m2 cisplatin (CDDP). A continuous group is intravenous bolus injection of 2.5 mg azasetron followed by 7.5 mg continuous intravenous infusion for 24 hrs, and a bolus group is intravenous bolus injection of 10 mg azasetron. The inhibitory effect on nausea of the continuous group was significantly superior to those of the bolus group on day 3 and 4 (p < 0.05) and inhibitory effect on vomiting of the continuous group was significantly superior to those of bolus group on day 2 (p < 0.05). No adverse effects were observed in either group of this study. From these data, continuous intravenous infusion of azasetron was considered to be highly effective in prophylaxis of nausea and vomiting induced by anticancer drugs.     

Prevention of emesis by tropisetron in children receiving combined chemotherapy with cisplatin

We evaluated the antiemetic efficacy of tropisetron, a 5-HT3 receptor antagonist, during its use in 15 children with malignant disease who received cisplatin (CDDP) either alone (1/15) or in combination (14/15) with other cytostatic drugs. Tropisetron was given to 15 children (8 boys and 7 girls, ranging from 6 months to 17 years of age) with miscellaneous neoplasms. Generally, tropisetron (5 mg/m2/day, maximum 5 mg/day) was administered intravenously the first day of CDDP-based chemotherapy and orally for 4 subsequent days of chemotherapy. The dose of tropisetron was reduced to 0.2 mg/kg/day in children less than 1 year of age and/or those weighing less than 10 kg. Vomiting and nausea were controlled completely in 8 of 15 (53.3%) children on day 1 with a single intravenous infusion of tropisetron. Partial control was observed in 40% of patients on day 1. Complete control of delayed nausea and vomiting ranged between 40% and 80% in patients over days 2 to 5. The results obtained during administration of tropisetron confirm that it is a valid, safe, and manageable antiemetic for the treatment of malignant disease in pediatric patients.     

Calcium antagonists--clinical considerations

BACKGROUND: Postoperative nausea and vomiting (PONV) following major arthroplasty with spinal anaesthesia and intrathecal morphine is reported in 45-74% of patients. This randomised, double-blind, placebo-controlled trial was undertaken to determine whether a subhypnotic infusion of propofol has a prophylactic antiemetic effect in this patient population. METHODS: 82 patients undergoing hip or knee replacement under subarachnoid bupivacaine anaesthesia plus morphine 0.25 mg were randomised at the end of surgery to receive either propofol 30 mg x h(-1) or fat emulsion (Intralipid) 3 ml x h(-1) for 20 h postoperatively. Blinded observers recorded episodes of nausea, vomiting and pruritus. RESULTS: PONV in the intervention group was 40% vs 59% in the controls (P=0.1, not significant). Pruritus occurred in 34%, with a similar rate in both groups. CONCLUSION: These results suggest that routine use of postoperative, subhypnotic propofol infusion as PONV prophylaxis is not justified in this patient population.     

Early neuropsychological impairment in HIV-seropositive intravenous drug users: evidence from the Italian Multicentre Neuropsychological HIV Study

The purpose of this study was to document the emetogenic potential of intrathecal chemotherapy (IC) in children and to evaluate the efficacy of ondansetron in reducing nausea and vomiting with this chemotherapy treatment. Patients less than 18 years of age with acute lymphoblastic leukemia were eligible to participate in a survey project measuring the emetogenic potential of various chemotherapy treatments. Patients surveyed for 1 or more IC treatments were included in this report. The IC consisted of methotrexate, hydrocortisone and cytarabine, dosed according to patient age. A nausea/vomiting survey instrument was completed by each patient and/or parent following IC treatment. The instrument rated nausea, vomiting and daily activity interference (DAI) on a 4-point scale of 0 = none, 1 = mild, 2 = moderate and 3 = severe, and collected data on the number of vomiting and/or retching episodes in addition to the child's appetite following the chemotherapy treatment. When ondansetron was employed, it was administered in an i.v. infusion at a dose of 0.15 mg/kg before and after chemotherapy or as an oral dose of 4 mg or 8 mg before chemotherapy. Courses of IC without antiemetics were analyzed to determine the emetogenic potential of IC. For patients receiving IC both with and without ondansetron, courses were compared with each patient used as their own control to determine the influence of ondansetron upon survey responses. Statistical analysis consisted of nonparametric Friedman 2-way ANOVA for ordinal variables and a paired t-test for continuous variables. The binomial test was employed to analyze for differences between ondansetron and no antiemetic in the number of patients with complete control of both nausea and vomiting or vomiting alone. A total of 63 children with a mean age of 7.6 +/- 4.2 years were each studied on one or more occasions. Thirty-seven children were surveyed for 87 IC treatments without antiemetics (group I), and 17 children from this group were surveyed for 48 IC courses with i.v. ondansetron (group IA). An additional 18 children were subsequently surveyed for 39 IC courses with i.v. ondansetron (group II). Fifteen patients (7 of whom were members of group I) were surveyed following 33 IC courses with oral ondansetron (group III). The survey scores for group I patients were: nausea severity 1.3 +/- 1.1, vomiting severity 1.2 +/- 1.1, DAI 1.2 +/- 1.0 and mean number of emetic episodes 4.7 +/- 8.4. The mean appetite score was 1.5 +/- 1.1. For patients in group IA, nausea severity (0.8 +/- 0.9), vomiting severity (0.5 +/- 0.8), DAI (0.7 +/- 0.8), and the number of emetic episodes (1.4 +/- 2.8) were all significantly lower than with prior IC treatments without ondansetron. For complete protection, children receiving i.v. ondansetron had greater complete protection rates from both nausea and vomiting or vomiting alone than did patients receiving no antiemetic. Survey responses were also lower for patients receiving oral ondansetron, but insufficient control data did not allow for statistical analysis. IC results in mild to moderate nausea and vomiting in children. The emetogenic potential of IC is significantly reduced by i.v. ondansetron.     

Relation between impedance and electrode temperature during radiofrequency catheter ablation of accessory pathways and atrioventricular nodal reentrant tachycardia

OBJECTIVES: To evaluate and compare the clinical efficacy, impact on hemodynamics, safety profiles, and cost of combined administration of propofol and midazolam (synergistic sedation) vs. midazolam and propofol administered as sole agents, for sedation of mechanically ventilated patients after coronary artery bypass grafting. DESIGN: Prospective, controlled, randomized, double-blind clinical trial. SETTING: Intensive care unit of SCIAS-Hospital de Barcelona. PATIENTS: Seventy-five mechanically ventilated patients who underwent coronary artery bypass graft surgery under low-dose opioid anesthesia. INTERVENTIONS: According to the double-blind method, patients were randomly assigned to receive propofol (n = 25), midazolam (n = 25), or propofol combined with midazolam (n = 25). Infusion rates were adjusted to stay between 8 and 11 points on Glasgow Coma Score modified by Cook and Palma. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD duration of sedation was 14.4 +/- 1.5 hrs, 14.1 +/- 1.1 hrs, and 14.7 +/- 1.9 hrs for the propofol, midazolam, and synergistic groups, respectively. The induction dose was 0.55 +/- 0.05 mg/kg for propofol as sole agent, 0.05 +/- 0.01 mg/kg for midazolam as sole agent, and 0.22 +/- 0.03 mg/kg for propofol administered in combination with 0.02 +/- 0.00 mg/kg of midazolam (p = .001). The maintenance dose was 1.20 +/- 0.03 mg/kg/hr for propofol as sole agent, 0.08 +/- 0.01 mg/kg/hr for midazolam as sole agent, and 0.50 +/- 0.09 mg/kg/hr for propofol administered in combination with 0.03 +/- 0.01 mg/kg/hr of midazolam (p < .001). All sedative regimens achieved similar efficacy in percentage of hours of adequate sedation (93% for propofol, 88% for midazolam, and 90% for the synergistic group, respectively). After induction, both propofol and midazolam groups had significant decreases in systolic blood pressure, diastolic blood pressure, left atrial pressure, and heart rate. Patients in the synergistic group had significant bradycardia throughout the study, without impairment in other hemodynamic parameters. Patients sedated with propofol or synergistic regimen awoke sooner and could be extubated before those patients sedated with midazolam (0.9 +/- 0.3 hrs and 1.2 +/- 0.6 hrs vs. 2.3 +/- 0.8 hrs, respectively, p = .01). Synergistic sedation produced cost savings of 28% with respect to midazolam and 68% with respect to propofol. CONCLUSIONS: In the study conditions, the new synergistic treatment with propofol and midazolam administered together is an effective and safe alternative for sedation, with some advantages over the conventional regimen with propofol or midazolam administered as sole agents, such as absence of hemodynamic impairment, >68% reduction in maintenance dose, and lower pharmaceutical cost.     

Endocrine stress reaction, hemodynamics and recovery in total intravenous and inhalation anesthesia. Propofol versus isoflurane

This prospective, randomised study compared total intravenous anaesthesia (TIVA) and inhalation anaesthesia with respect to endocrine stress response, haemodynamic reactions, and recovery. METHODS. The investigation included two groups of 20 ASA I-II patients 18-60 years of age scheduled for orthopaedic surgery. For premedication of both groups, 0.1 mg/kg midazolam was injected IM. Patients in the propofol group received TIVA (CPPV, PEEP 5 mbar, air with oxygen FiO2 33%) with propofol (2 mg/kg for induction followed by an infusion of 12-6 mg/kg.h) and fentanyl (0.1 mg before intubation, total dose 0.005 mg/kg before surgery, repetition doses 0.1 mg). For induction of patients in the isoflurane-group, 5 mg/kg thiopentone and 0.1 mg fentanyl was administered. Inhalation anaesthesia was maintained with 1.2-2.4 vol.% isoflurane in nitrous oxide and oxygen at a ratio of 2:1 (CPPV, PEEP 5 mbar). For intubation of both groups, 2 mg vecuronium and 1.5 mg/kg suxamethonium were injected, followed by a total dose of 0.1 mg/kg vecuronium. Blood samples were taken through a central venous line at eight time points from before induction until 60 min after extubation for analysis of adrenaline, noradrenaline (by HPLC/ECD), antidiuretic hormone (ADH), adrenocorticotropic hormone (ACTH), and cortisol (by RIA). In addition, systolic arterial pressure (SAP) heart rate (HR), arterial oxygen saturation (SpO2), and recovery from anaesthesia were observed. RESULTS. Group mean values are reported; biometric data from both collectives were comparable (Table 1). Plasma levels of adrenaline (52 vs. 79 pg/ml), noradrenaline 146 vs. 217 pg/ml), and cortisol (82 vs. 165 ng/ml) were significantly lower in the propofol group (Table 2, Figs. 1 and 3). Plasma levels of ADH (4.8 vs. 6.1 pg/ml) and ACTH (20 vs. 28 pg/ml) did not differ between the groups (Table 2, Figs 2 and 3). SAP (128 vs. 131 mmHg) was comparable in both groups, HR (68/min vs. 83/min) was significantly lower in the propofol group, and SpO2 (97.1 vs 97.4%) showed no significant difference (Table 3). Recovery from anaesthesia was slightly faster in the propofol group (following of simple orders 1.9 vs. 2.4 min, orientation with respect to person 2.4 vs. 3.4 min, orientation with respect to time and space 2.8 vs. 3.7 min), but differences failed to reach statistical significance. CONCLUSIONS. When compared with isoflurane inhalation anaesthesia, moderation of the endocrine stress response was significantly improved during and after TIVA with propofol and fentanyl. Slightly shorter recovery times did not lead to an increased stress response. With respect to intra- and postoperative stress reduction, significant attenuation of sympatho-adrenergic reaction comparable SAP and reduced HR, sympatholytic and hypodynamic anaesthesia with propofol and fentanyl seems to be advantageous for patients with cardiovascular and metabolic disorders. For this aim, careful induction and application of individual doses is essential.     

Temperature-dependent formation of a conjugate between tris(hydroxymethyl)aminomethane buffer and the malondialdehyde-DNA adduct pyrimidopurinone

OBJECTIVE: To examine the effects of cardiopulmonary bypass (CPB) on total and unbound plasma concentrations of propofol and midazolam when administered by continuous infusion during cardiac surgery. DESIGN: Prospective clinical study. SETTING: University hospital. PARTICIPANTS: Twenty-four adult patients undergoing cardiac surgery. INTERVENTIONS: Patients received either propofol or midazolam to supplement fentanyl anesthesia. Twelve patients received a propofol bolus (1 mg/kg) followed by an infusion of 3 mg/kg/hr. A second group received midazolam, 0.2 mg/kg bolus, followed by an infusion of 0.07 mg/kg/hr. MEASUREMENTS AND MAIN RESULTS: Blood sample were collected from the radial artery cannula at 0, 2, 4, 8, 8, 10, 15, 20 minutes and then every 10 minutes before CPB, at 1, 2, 3, 4, 6, 10, 15, 20 minutes and then each 10 minutes during CPB. On weaning from CPB samples were collected at 0, 5, 10 and 20 minutes. Plasma binding, total and unbound propofol and midazolam concentrations were determined by ultrafiltration and high-pressure liquid chromatography (HPLC). CPB resulted in a fall in total propofol and midazolam plasma concentrations, but the unbound concentrations remained stable. The propofol unbound fraction increased from 0.22 +/- 0.06% to 0.41 +/- 0.17%. The midazolam unbound fraction increased from 5.6 +/- 1.0% to 11.2 +/- 2.1%. CONCLUSIONS: Unbound concentrations of propofol and midazolam are not affected by cardiopulmonary bypass. Total intravenous anesthesia algorithms do not need to be changed to achieve stable unbound plasma concentrations when initiating CPB.     

Familial inv(X) (p22q22): ovarian dysgenesis in two sisters with del Xq and fertility in one male carrier

PURPOSE: To evaluate the antiemetic efficacy and safety of adding the dopamine antagonist prochlorperazine to the combination of granisetron and dexamethasone in the prevention of acute nausea and vomiting following high-dose cisplatin. PATIENTS AND METHODS: Sixty patients receiving cisplatin (> or = 75 mg/m2) (median dose = 100 mg/m2) were enrolled at three sites. Patients received prochlorperazine spansule 15 mg orally, 60 minutes prior to and 12 hours after cisplatin; dexamethasone 20 mg intravenously, 45 minutes prior to cisplatin, and 10 mg intravenously or orally, 12 hours after cisplatin; and granisetron 10 micrograms/kg intravenously, 30 minutes prior to cisplatin. Efficacy was assessed during the 24-hour period after cisplatin using complete antiemetic response (no emetic episodes and no rescue antiemetics) and patient assessment of nausea and satisfaction using 100-mm visual analog scales (nausea: 0 = none, 100 = nausea as bad as it can be; satisfaction: 0 = not at all satisfied, 100 = satisfied as can be). RESULTS: Complete response (0 emetic episodes) was noted in 84% (49/58) of patients. Forty-two patients (72%) experienced no nausea. The mean change in posttreatment nausea visual analog scales from baseline was 8.9 mm. Forty-eight patients (83%) were completely satisfied with their antiemetic treatment. The mean posttreatment patient satisfaction score was 92 mm. Treatment was well tolerated, with infrequent and minor adverse events. CONCLUSIONS: This three-drug antiemetic regimen is well tolerated and highly effective in the prevention of acute nausea and vomiting arising from high-dose cisplatin. Further studies evaluating this regimen are warranted.     

Antiemetic efficacy of prophylactic ondansetron in laparoscopic surgery: randomized, double-blind comparison with metoclopramide

In a randomized, double-blind study, we have compared the prophylactic antiemetic efficacy of ondansetron with that of metoclopramide in 123 patients undergoing general anaesthesia for day-case gynaecological laparoscopic surgery. The patients received either i.v. ondansetron 4 mg or metoclopramide 10 mg immediately before a standard anaesthetic. The number of patients with no nausea or vomiting in the ondansteron group was 50 (82%) compared with 29 (47%) in the metoclopramide group (P < 0.001). In those patients with a previous history of postoperative nausea and vomiting, nausea was less severe in those receiving ondansetron compared with those receiving metoclopramide (P < 0.05). We conclude that preoperative prophylactic administration of i.v. ondansetron was superior to metoclopramide in preventing nausea and vomiting after general anaesthesia for day-case gynaecological laparoscopic surgery.     

Comparison of eltanolone and propofol in anesthesia for termination of pregnancy

A randomized study was designed to compare eltanolone (pregnanolone) and propofol anesthesia in 60 unpremedicated women undergoing outpatient termination of pregnancy. The initial doses for induction of anesthesia were 0.8 mg/kg for eltanolone and 2 mg/kg for propofol followed by an additional 25% increment if necessary. The doses required for successful induction were 0.82 +/- 0.06 and 2.1 +/- 0.3 (mean +/- SD) mg/kg for eltanolone and propofol, respectively. Discomfort or pain on injection occurred in none of the patients given eltanolone and in 20% of those receiving propofol (P < 0.05). To maintain satisfactory anesthesia, 29% of the patients given eltanolone and 70% of the patients given propofol needed extra bolus doses of the study drug (P < 0.01). Excitation (twitching of extremities or slight hypertonus) occurred in 29% of the patients in the eltanolone group compared to none in the propofol group (P < 0.05). Both clinical (opening eyes, orientation, walking, tolerating oral fluids, voiding) and psychomotor recovery (Maddox Wing test and Digit Symbol Substitution test) returned to baseline more slowly after eltanolone than after propofol. Overall home readiness was achieved later in the eltanolone group [median 57 min (range 41-190 min)] compared to the propofol [37 (32-100 min)] group. We conclude that recovery from anesthesia is more rapid from propofol as compared to eltanolone anesthesia.     

Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies

The association of propofol with excitatory motor activity, such as myoclonic jerking and opisthotonus, in humans and in animals suggests that it may aggravate clinical seizure activity in some circumstances, although evidence suggests that under other circumstances, propofol inhibits seizure activity. In the current study, we assessed the effect of sedating doses of propofol on lidocaine-induced seizure activity in spontaneously breathing rats receiving no other anesthetics. Adult Sprague-Dawley male rats, 300-400 g, were divided into a control group and three experimental groups representing three graded levels of propofol sedation. The control rats then received a lidocaine infusion at the rate of 150 mg x kg(-1) x h(-1), resulting in a slow, progressive increase in systemic lidocaine concentrations. At the onset of electroencephalographic (EEG) seizure activity, arterial lidocaine concentrations were obtained. The treated rats received propofol according to three different dose schedules: Dose 1 = 10 mg x kg(-1) x h(-1) after a 2.5-mg/kg bolus; Dose 2 = 20 mg x kg(-1) x h(-1) after a 5-mg/kg bolus; Dose 3 = 40 mg x kg(-1) x h(-1) after a 10-mg/kg bolus. After 30 min, a steady level of sedation, dependent on the dose of propofol, was achieved. The lidocaine infusion was then started, and systemic lidocaine levels were obtained at the onset of EEG seizure activity. The lidocaine was continued until the onset of death by cardiac arrest. Plasma lidocaine was measured by gas chromatography. Analysis of variance and Dunnett's t-test were used for comparisons with the control values. Continuous propofol sedation increased the seizure dose of lidocaine from 37.7 +/- 3.5 mg/kg (mean +/- SEM) to 52.5 +/- 2.6 mg/kg (Dose 1, P < 0.05) and 67.9 +/- 8.6 mg/kg (Dose 2, P < 0.05), and completely abolished lidocaine seizures at Dose 3. The lethal dose of lidocaine, 89.4 +/- 10.5 mg/kg control versus 108.7 +/- 10.3 mg/kg (Dose 1), 98.3 +/- 10.1 mg/kg (Dose 2), and 93.5 +/- 10.4 mg/kg (Dose 3) did not differ among groups. The lidocaine levels at seizure threshold were increased in the propofol-treated rats: 16.9 +/- 0.5 microg/mL control versus 19.2 +/- 0.7 microg/mL (Dose 1, P = not significant) and 23.7 +/- 1.8 microg/mL (Dose 2, P < 0.05). Continuous propofol sedation in spontaneously breathing rats receiving no other anesthetics exerts a protective effect against lidocaine-induced seizures in a monotonic, dose-dependent fashion. The cardiac arrest dose of lidocaine is unaffected by propofol under these conditions. IMPLICATIONS: The i.v. anesthetic drug propofol, given to rats to produce sedation, was found to suppress seizure activity caused by overdosage of the local anesthetic lidocaine.