Ondansetron has similar clinical efficacy against both nausea and vomiting.

Ondansetron is widely believed to prevent postoperative vomiting more effectively than nausea. We analysed data from 5161 patients undergoing general anaesthesia who were randomly stratified to receive a combination of six interventions, one of which was 4 mg ondansetron vs placebo. For the purpose of this study a 20% difference in the relative risks for the two outcomes was considered clinically relevant. Nausea was reduced from 38% (969/2585) in the control to 28% (715/2576) in the ondansetron group, corresponding to a relative risk of 0.74, or a relative risk reduction of 26%. Vomiting was reduced from 17% (441/2585) to 11% (293/2576), corresponding to a relative risk of 0.67, or a relative risk reduction of 33%. The relative risks of 0.67 and 0.74 were clinically similar and the difference between them did not reach statistical significance. We thus conclude that ondansetron prevents postoperative nausea and postoperative vomiting equally well.

Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery.

BACKGROUND: Multimodal pain management has been suggested to improve postoperative analgesia. In this study, we evaluated the quality of analgesia in women undergoing day-case gynaecological laparoscopic surgery, after premedication with pregabalin 75 mg (P75) or 150 mg (P150), compared with diazepam 5 mg (D5). All patients were given ibuprofen 800 mg orally. METHODS: Altogether 90 consenting women were anaesthetized in a standardized fashion. Postoperative analgesia was provided by ibuprofen 800 mg twice a day with fentanyl i.v. on request in the recovery room (RR), and combination tablets with acetaminophen and codeine after the RR. The visual analogue scale (VAS) scores for pain and side-effects and the amounts of postoperative analgesics were recorded for 24 h after surgery. The areas under the curves (AUC) were calculated for the VAS scores for pain at rest, pain in motion, and pain at cough 1-8 and 1-24 h after surgery. RESULTS: The median AUC values for VAS scores for pain at rest (P=0.048) and in motion (P=0.046) 1-8 h after surgery were lower in the P150 group than that in the D5 group. The amounts of rescue analgesics or the degree of drowsiness did not differ in the three study groups. CONCLUSIONS: Analgesia was better after premedication with pregabalin 150 mg than after diazepam 5 mg, both with ibuprofen 800 mg, during the early recovery after day-case gynaecological laparoscopic surgery. Pregabalin 150 mg did not reduce the amount of postoperative analgesics required.

Intravenous remifentanil vs. epidural levobupivacaine with fentanyl for pain relief in early labour: a randomised, controlled, double-blinded study.

BACKGROUND: We hypothesised that intravenous patient-controlled analgesia (IV PCA) with remifentanil could provide as satisfactory pain relief for labour as epidural analgesia. METHODS: Fifty-two parturients with singleton uncomplicated pregnancies were randomised to receive either IV PCA with remifentanil or epidural analgesia with 20 ml levobupivacaine 0.625 mg/ml and fentanyl 2 microg/ml in saline. The PCA dose of remifentanil was given over 1 min with a lockout time of 1 min. The dose was increased starting from the bolus of 0.1 microg/kg and following a dose escalation scheme up until the individual-effective dose was reached. The parturients assessed contraction pain (0-10), pain relief (0-4), sedation and nausea during 60 min. RESULTS: Forty-five parturients were included in the analysis. The median cervical opening was 4 cm before the study and 7 cm after the study. The median pain scores were 7.3 and 5.2 during remifentanil and epidural analgesia, respectively (P=0.009). The median pain relief scores were 2.5 and 2.8 (P=0.17). There was no difference between the groups in the proportion of parturients who discontinued due to ineffective analgesia, nor in the proportion of parturients who would have liked to continue the given medication at the end of the study. Sedation and low haemoglobin oxygen saturation were observed more often during remifentanil analgesia. Foetal heart rate tracing abnormalities were as common in both groups. CONCLUSIONS: In terms of pain scores, epidural analgesia is superior to that provided by IV remifentanil. However, there was no difference in the pain relief scores between the treatments.

Diazepam effects and kinetics in Caucasians and Orientals.

Mental and psychomotor effects and diazepam kinetics were studied in Caucasian and Orientals. 12 Caucasian and 13 Oriental young adults received on one of two occasions, separated by 2 weeks, either 0.2-mg/kg diazepam or saline intravenously. Serum diazepam and desmethyldiazepam concentrations were measured by electron-capture gas-liquid chromatography in samples drawn up to 72 hr after injection. Serum protein binding was measured by equilibrium dialysis. Subjects were tested on a battery of psychological tests before and 0.5, 2, and 4 hr after treatment. While the free fraction of diazepam was identical in both races (0.02), volume of distribution at steady state (Vdss) was different when calculated as absolute volume (Vdss = 76.55 +/- 9.63 l in Caucasians and 54.96 +/- 4.55 l in Orientals, p = 0.04) and marginally significant when corrected for body weight (Vdssl/kg = 1.10 +/- 0.11 in Caucasian and 0.88 +/- 0.05 in Orientals, p = 0.07). total body clearance (Cl), but not elimination half-life (t 1/2), was higher in Caucasians than Orientals, p less than 0.01; t 1/2 = 37.70 +2- 5.53 hr in Caucasians and 41.77 +/- 3.80 in Orientals). Desmethyldiazepam levels were higher in Orientals than Caucasians. Mental and psychomotor effects were maximal at the first session (0.5 hr), followed by complete recovery by the 4-hr session. Effects were similar in both groups. If repeated dosing causes a higher rate of cumulated diazepam serum levels in Orientals, as expected, there might be deeper brain depression in that group.

Tofisopam, a novel 3,4-benzodiazepine: multiple-dose effects on psychomotor skills and memory. Comparison with diazepam and interactions with ethanol.

Twelve healthy male volunteers were treated (double-blind crossover design) with tofisopam (a new 3,4-benzodiazepine), diazepam, or placebo, on 2 consecutive days each. Psychomotor skills were impaired after a single dose of diazepam (10 mg) given on day 1. Measurements on day 2 showed that some tolerance had developed to the diazepam-induced impairment of reactive and coordinative skills, but not to its effects on flicker fusion or on the extraocular muscle balance. Tofisopam failed to impair performance both as a single dose (100 mg) and after repeated doses (100 + 50 + 50 + 100 mg). The subjects felt more fatigue, dizziness, calmness, and passiveness after diazepam than after tofisopam. When either drug was given together with 0.8 g/kg ethanol on day 2, the breath ethanol concentrations were 0.7--1.0 mg/ml and all psychomotor skills were impaired. Diazepam + ethanol particularly impaired memory and learning as well. After this combination the subjects were classified (time anticipation test) as 'disqualified drivers' more often than after placebo. It is concluded that diazepam, as well as either benzodiazepine with ethanol, may reduce the ability to drive vehicles or operate machinery.

Effect of hydroxyethyl starch and dextran on plasma volume and blood hemostasis and coagulation.

Six healthy male subjects were given in a crossover fashion medium molecular weight (HES 125) and low molecular weight (HES 40) hydroxyethyl starch, dextran, and balanced salt solution by intravenous infusion. The plasma volumes were determined using labeled albumin and plasma protein measurements. Three properties of factor VIII protein complex and indices of blood coagulation and hemostasis were measured before and after the infusions. Both the salt solution and HES 40 increased plasma volume, but their effect wore off within 3 hours. Dextran and HES 125 increased plasma volume significantly (P less than 0.001) more than the salt solution did, and the expansion was maintained for 24 hours. Plasma volume increases (dextran and HES 125) were associated with high nonglucose carbohydrate levels in plasma and low levels in urine. No or slight increases in plasma volumes (HES 40), on the other hand, were associated with low and high carbohydrate levels in plasma and urine, respectively. Serum alpha-amylase activity increased significantly after both HES preparations as compared to salt solution. Dextran and HES 125 decreased all the three values of factor VIII, these decreases being maximal 3 to 6 hours after administration and highest (about 25 per cent) for F VIII R:Ag and F VIII R:cof. It is concluded that HES 125 and dextran are equally effective plasma expanders.

Clinical effectiveness and untoward effects of new agents and techniques used in intravenous sedation.

An ideal i.v. sedative for dentistry should provide anti-anxiety and analgesic activity, amnesic action, and patient cooperation without depression of the cardiorespiratory system and with rapid recovery. Lorazepam does not provide any advantages over the currently available agents, but midazolam, a new water-soluble benzodiazepine, and later selective benzodiazepine receptor antagonists may play an important role in outpatient sedation.

Nitrous oxide and human state-dependent memory.

State-dependent effects of nitrous oxide on human memory were examined by administering serial and paired-associate learning tasks to subjects receiving 20 and 30% nitrous oxide or placebo. Nitrous oxide in 30% concentration impaired learning of both tasks. In addition, it produced an atypical form of asymmetric state-dependent memory; subjects who learned while receiving placebo and recalled while receiving nitrous oxide displayed the worst recall.

Effect of intravenous diazepam and thiopental on voluntary saccades and pursuit eye movements.

The effects of diazepam and thiopental on voluntary saccades and pursuit eye movements were tested in 9 volunteers, with an interval of at least 2 weeks between tests. One, 4 and 8 h after intravenous injection of diazepam (0.3 mg/kg) or thiopental (6.0 mg/kg), voluntary saccades and pursuit eye movements were tested and blood samples taken for analysis of drug concentration. As compared to results of tests without drugs, a significant reduction both of saccadic peak velocity and gain of pursuit eye movements was found 1 h after injection of either drug, but not after 4 and 8 h. The amplitude of saccades elicited with the 60 degrees stimulus was significantly reduced 1 h after injection of diazepam. Latency of saccades increased significantly up to 4 h after injection of either drug. No significant correlation was found between peak velocity of saccades and blood concentration of either thiopental or diazepam 1 h after administration. The present results confirm that in man saccades and pursuit eye movements are reduced by benzodiazepines and barbiturates, but provide no support for the previously described efficacy of saccades in monitoring the effect of benzodiazepines. It is hypothesized that diazepam and thiopental also induce reduction of voluntary saccades and pursuit eye movements via a general sedation of the central nervous system (CNS), besides having specific effects on CNS structures important to the performance of voluntary eye movements.

Reduction of gain and time constant of vestibulo-ocular reflex in man induced by diazepam and thiopental.

The effect of intravenous administration of two sedatives, diazepam (0.3 mg/kg) and thiopental (6.0 mg/kg), on the vestibulo-ocular reflex (VOR) in man was investigated on 9 volunteers. The VOR was evoked with a velocity step rotation test and gain and time constant of prerotatory and postrotatory nystagmus were measured. Both drugs reduced VOR gain. Diazepam-induced reduction lasted 8 h and thiopental-induced reduction 1 h. A reduction of the VOR time constant was found lasting about 1 h for both drugs, but with a tendency for the thiopental effect to last longer. These findings, not previously described in man, differ from what has been found in macaques and rabbits injected with diazepam. The reduction of gain and time constant were not correlated with the blood concentration of either drug. The present results suggest that in man the VOR gain and time constant are both reduced by different types of sedatives although with different time courses. On the basis of previously shown effect of alertness on the VOR, it is hypothesized that diazepam and thiopental, besides having a specific effect on central nervous system structures important to the VOR, also induce reduction of the VOR through a general sedation of the CNS.

Comparison of dexmedetomidine and midazolam sedation and antagonism of dexmedetomidine with atipamezole.

STUDY OBJECTIVE: To evaluate the effects of dexmedetomidine, an alpha-2 agonist, as an intravenous sedative drug and the effects of atipamezole, an alpha-2 antagonist, on recovery. DESIGN: Randomized, double-blind study with three parallel groups. An open dose-finding study preceded it to optimize the atipamezole dose. SETTING: Outpatient operating room at the gynecologic and obstetric university hospital in Helsinki, Finland. PATIENTS: Seventy-two healthy women scheduled for legal termination of pregnancy. INTERVENTIONS: Patients were assigned to one of three groups of 24 patients each to receive either dexmedetomidine 2 micrograms/kg and atipamezole 50 micrograms/kg; dexmetomidine 2 micrograms/kg and saline; or midazolam 0.15 mg/kg and saline. In addition to paracervical block, each patient received two different study drugs: study drug 1 was a sedative agent (either dexmedetomidine or midazolam), administered before the procedure. If the sedation was not deep enough and the patient reacted to the procedure, a low dose of propofol was administered. Study drug 2 was a reversing agent or a placebo, administered following the procedure. MEASUREMENTS AND MAIN RESULTS: The mean time to regain consciousness was shorter in the dexmedetomidine-atipamezole and the dexmedetomidine-saline groups compared with the midazolam group. Postoperative sedation, tested both by subjective and objective assessments, decreased more quickly in the dexmedetomidine-atipamezole group compared with the dexmedetomidine-saline and the midazolam groups. CONCLUSION: Atipamezole is an effective antagonist for reversing psychomotor impairment following dexmedetomidine sedation.

Oral dolasetron mesylate for prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study. The Oral Dolasetron PONV Prevention Study Group.

STUDY OBJECTIVE: To examine the safety and effectiveness of a range of single oral doses of dolasetron mesylate for the prevention of postoperative nausea and vomiting. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 32 hospitals. PATIENTS: 789 female ASA physical status I, II, and III patients, ages 18 to 60 years, weighing between 45 and 100 kg, scheduled for major gynecologic surgery (including abdominal hysterectomy, gynecologic laparotomy, or vaginal hysterectomy) with general anesthesia. INTERVENTIONS: 25, 50, 100, or 200 mg oral doses of dolasetron mesylate or placebo were administered 1 to 2 hours before induction of anesthesia. Efficacy was assessed for 24 hours postrecovery by measuring complete response (no emetic episodes, no rescue medication), total response (complete response with no nausea), time to first emetic episode or rescue, and patient visual analog scale evaluations of nausea severity and satisfaction with antiemetic therapy. MEASUREMENTS AND MAIN RESULTS: Complete response rates for the 50, 100, and 200 mg dose groups were statistically greater than placebo (p < or = 0.018). Likewise, total response rates were statistically greater in the 50, 100, and 200 mg dose groups than in the placebo group (p = 0.012). Percentage of patients with no nausea and patient satisfaction scores were significantly higher for each dolasetron dose group than placebo (p < or = 0.047 and p < or = 0.004, respectively). Efficacy peaked at the 50 mg dose. The incidence of adverse events was similar in the placebo (30.1%) and dolasetron groups (29.4%). Headache was the most frequent treatment-related adverse event, with 2% to 5% incidence across groups. Incidence of adverse events did not increase with increasing dolasetron doses. Dose-related decreases in blood pressure at acute time points were not clinically significant. CONCLUSION: Single oral doses of dolasetron, administered 1 to 2 hours before induction of anesthesia, are safe and effective for preventing postoperative nausea and vomiting in this patient sample. Maximal antiemetic response was seen with the 50 mg oral dolasetron dose.

Local anesthetic techniques for bronchoscopies.

Local anesthetic techniques are often preferable to general anesthesia for bronchoscopies since these examinations are mostly undertaken as outpatient procedures. To be successful bronchoscopy under local anesthesia must satisfy three criteria: the technique used must produce adequate anesthesia: the procedure must be safe: and the technique should be easy for the patient as well as for the physician. Local anesthesia of the respiratory tract for these procedures can be achieved by laryngotracheal spraying or ultrasonic nebulizer administration of lidocaine. For fiberoscopic procedures lidocaine can also be administered through the fiberoscope. When the local anesthetic techniques are supplemented with light sedation, the procedure is easier and more acceptable to the patients. Using small doses of diazepam, flunitrazepam, or midazolam i.v. one can produce amnesia for the procedure and still discharge the patients 2 h after the procedure with a responsible adult. In many cases local anesthesia supplemented by intravenous sedation is a proper alternative and should be preferred to general anesthesia in ambulatory practice for diagnostic bronchoscopies.

Full recovery after different anesthesia techniques for short diagnostic procedures.

When suitable, local anesthetic techniques are preferable for ambulatory short diagnostic procedures. If general anesthesia is used no or only very light premedication, induction with a short acting i.v. agent and the maintenance of anesthesia with nitrous oxide plus oxygen plus an inhalational agent or alternatively with short acting i.v. anesthetic and analgesic seems today to provide fastest recovery. Patients should always arrange for a responsible adult to accompany them home. Minimal requirements for safe discharge should in addition to stable vital signs and the ability to maintain oral fluids include that patients are able to dress themselves and able to walk out. These criteria, however, do not indicate that patients are fully recovered after anesthesia. In most cases patients are not fully recovered when discharged from hospital after even brief anesthesia and they should refrain from driving, operating machinery, and delay making important decisions for at least 24 hours after anesthesia.

Recovery following general anesthesia with isoflurane or enflurane for outpatient dentistry and oral surgery.

Anesthesia was induced in 120 unpremedicated, healthy patients undergoing outpatient dentistry or oral surgery with methohexital, and endotracheal intubation facilitated with succinylcholine. Anesthesia was maintained randomly with either enflurane or isoflurane in nitrous oxide and oxygen (50%) administered in a nonrebreathing circuit using spontaneous respiration. After both enflurane and isoflurane anesthesia, it took 12-13 minutes before the patients were oriented as to time and place. The patients' ability to walk along a straight line normalized significantly (p < .05) more quickly after isoflurane than after enflurane anesthesia. Long enflurane anesthesia (>90 minutes) was associated with a significantly (p < .05-p < .01) slower recovery of walking ability and of psychomotor performance in a perceptual speed test than was short enflurane anesthesia (<40 minutes). With isoflurane the speed of recovery did not depend on the duration of anesthesia. After both anesthetic techniques, 25-26% of the patients had nausea or vomited. We conclude that using spontaneous respiration recovery is faster after isoflurane anesthesia than after enflurane anesthesia and that isoflurane should be preferred to enflurane for long anesthesia of outpatients.

Continuous wound infusion with ropivacaine fails to provide adequate analgesia after caesarean section.

BACKGROUND: Continuous wound infusion with local anaesthetic has been used in post-caesarean pain management with conflicting results. We carried out a study comparing three groups: continuous ropivacaine wound infusion, intrathecal morphine with saline wound infusion and saline wound infusion only. METHODS: Sixty-six women undergoing elective caesarean section under combined spinal-epidural anaesthesia were randomly allocated to receive intrathecal morphine with saline wound infusion or 48 h continuous wound infusion with either ropivacaine or saline. All parturients received oral ketoprofen and intravenous oxycodone patient-controlled analgesia. Consumption of oxycodone, visual analogue scale pain scores (0-10 cm), patient satisfaction, side effects and recovery parameters were recorded for 48 h in a double-blind manner. RESULTS: Continuous wound infusion with ropivacaine failed to reduce oxycodone consumption or pain scores compared with saline control. In the first 24 h intrathecal morphine reduced mean oxycodone consumption compared to the ropivacaine wound infusion group (26 mg vs. 48 mg, P=0.007) and saline wound infusion group (26 mg vs. 45 mg, P=0.021). The first 24-h mean pain score was also lower in the intrathecal morphine group vs. the saline wound infusion group (1.3 vs. 2.2, P=0.021). Pain scores were not significantly different between intrathecal morphine and ropivacaine wound infusion groups. Pruritus was more common with intrathecal morphine. CONCLUSION: Compared to saline control, continuous wound infusion with ropivacaine failed to reduce the use of intravenous oxycodone patient-controlled analgesia or pain scores. Intrathecal morphine decreased oxycodone consumption by 46% in the first 24 h after surgery when compared to continuous ropivacaine wound infusion.

Persistent pain after caesarean section and vaginal birth: a cohort study.

BACKGROUND: Although persistent pain has been described to occur after various types of surgery, little is known about this entity following caesarean section or vaginal birth. We sought to examine the association between mode of delivery and development of persistent pain, as well as the nature and intensity of the pain. METHODS: A questionnaire was sent to 600 consecutive Finnish-speaking women within one year of their giving birth. The survey recorded the women's health history, obstetric history, previous pain, details of the caesarean section or vaginal birth, and a description of their pain, if present. RESULTS: Persistent pain one year after delivery was significantly more common after caesarean section (42/229, 18%) than after vaginal birth (20/209, 10%: P=0.011, OR 2.1 with 95% CI 1.2-3.7). The persistent pain was mild in 55% of the patients in both groups, and intense or unbearable for four caesarean sections and six vaginal births. Persistent pain was significantly more common in women with previous pain (P=0.013), previous back pain (P=0.016), and any chronic disease (P=0.016). The women with persistent pain recalled significantly more pain on the day after caesarean section (P=0.004) and vaginal birth (P=0.001) than those who did not report persistent pain. CONCLUSION: Persistent pain is more common one year after a caesarean section than after vaginal birth. A history of previous pain and pain on the day after delivery correlated with persistent pain.

The influence of ondansetron on the analgesic effect of acetaminophen after laparoscopic hysterectomy.

The 5-HT(3) antagonists tropisetron and granisetron have been shown to block the analgesic effect of acetaminophen in healthy volunteers. To study the interaction between ondansetron and acetaminophen in women undergoing laparoscopic hysterectomy, we randomized 134 patients into three groups to receive acetaminophen-placebo (AP), acetaminophen-ondansetron (AO), or placebo-placebo (PP). One gram of intravenous acetaminophen or placebo was administered at the induction of anesthesia and every 6 h thereafter for 24 h, and 4 mg of ondansetron or placebo was administered at the end of surgery. Pain control was provided by patient-controlled analgesia (PCA)-oxycodone. Acetaminophen (as compared to placebo) in periodic doses starting at induction of anesthesia reduced the total dosage of oxycodone required over 0-24 h (P = 0.031), but ondansetron given at the end of the surgery had no impact on the analgesic effect of acetaminophen (P = 0.723). The Numeric Rating Scale (NRS) scores for pain were similar whether ondansetron or placebo was administered at the end of the surgery. Therefore, it may be concluded that in women undergoing laparoscopic hysterectomy, the administration of periodic doses of intravenous acetaminophen (as compared to placebo) starting at induction of anesthesia reduces the total dose requirement of oxycodone, and a concomitant dose of a 5-HT(3) antagonist such as ondansetron at the end of the surgery does not block the analgesic effect of acetaminophen.