Multimodal therapies for postoperative nausea and vomiting, and pain.

Postoperative nausea and vomiting (PONV) and pain are two of the major concerns for patients presenting for surgery. The causes of PONV are multifactorial and can largely be categorized as patient risk factors, anaesthetic technique, and surgical procedure. Antiemetics work on several different receptor sites to prevent or treat PONV. This is probably why numerous studies have now demonstrated that using more than one antiemetic is usually more effective and results in fewer side-effects than simply increasing the dose of a single antiemetic. A multimodal approach to PONV should not be limited to drug therapy alone but should involve a holistic approach starting before operation and continuing intraoperatively with risk reduction strategies to which are added prophylactic antiemetics according to the assessed patient risk for PONV. With the increasing understanding of the pathophysiology of acute pain, especially the occurrence of peripheral and central hypersensitization, it is unlikely that a single drug or intervention is sufficiently broad in its action to be adequately effective, especially with moderate or greater pain. Although morphine and its congeners are usually the foundation of pain management regimens, as their dose increases so does the incidence of side-effects. Thus, the approach for the management of acute postoperative pain is to use multiple drugs or modalities (e.g. regional anaesthesia) to maximize pain relief and reduce side-effects.

Age-associated differences in the inhibition of mitochondrial permeability transition pore opening by cyclosporine A.

BACKGROUND: Inhibiting mitochondrial permeability transition pore (mPTP) opening is a key protection of the myocardium from ischemia/reperfusion (I/R) injury. Here, we investigated age-associated differences in the ability of cyclosporine A (CsA) to protect the heart and to modulate mPTP opening during I/R injury in vivo and its opening induced by reactive oxygen species (ROS) in vitro. METHODS: Fischer 344 male rats were assigned from their respective age groups, young or old groups, to (1) I/R or (2) I/R+CsA. All animals were subjected to 30 min of ischemia following 120 min of reperfusion to determine myocardial infarct size in vivo. To measure mPTP opening in vivo, left ventricular tissues were collected 10 min after reperfusion and nicotinamide adenine dinucleotide (NAD(+)) levels were measured. In parallel experiments, rat ventricular myocytes were prepared from young and old hearts, loaded with tetramethylrhodamine ethylester and then subjected to oxidative stress in the presence or absence of CsA, and the mPTP opening time was measured using laser scanning confocal microscopy. RESULTS: CsA reduced myocardial infarct size in young I/R rats. Whereas CsA failed to significantly affect myocardial infarct size in old I/R rats, NAD(+) levels were better preserved in young CsA-treated rats, but this relative improvement was not observed in old rats. CsA also significantly prolonged the time necessary to induce mPTP opening in young cardiomyocytes, but not in cardiomyocytes isolated from the old rats. CONCLUSIONS: mPTP regulation is dysfunctional in the aged myocardium and this could account for loss of cardioprotection with aging.

The effect of desflurane on rocuronium onset, clinical duration and maintenance requirements.

Volatile anesthetics potentiate the effects of non-depolarizing agents. This study investigated the interaction between the inhalational anesthetic desflurane and rocuronium. Forty ASA I and II patients randomly received desflurane/N2O/fentanyl, or propofol/ N2O/fentanyl anesthesia, and rocuronium 0.6 mg/kg. Neuromuscular block was assessed at the adductor pollicis muscle. Block onset and clinical duration times were measured; a rocuronium infusion was started when the first twitch on train-of-four returned to 10% of control (T10%). Maintenance infusion requirements and recovery profiles (spontaneous and after reversal) were recorded until recovery of twitch to 90% of control (T90%). Rocuronium onset was prolonged by 67% (p = 0.034), clinical duration by 30% (p = NS), and infusion requirements were lower in the desflurane group (4.5 vs. 7.1 mg/kg/min, p = 0.003). Recovery times were not statistically different. Desflurane significantly delays the onset of neuromuscular block, potentiates rocuronium during maintenance infusion, but does not affect clinical duration or recovery.

Does functional ability in the postoperative period differ between remifentanil- and fentanyl-based anesthesia?

STUDY OBJECTIVES: To compare patients' functional ability in the 24-hour postoperative period following a remifentanil compared to a hypnotic-fentanyl-treated anesthesia regimen using a 24-Hour Functional Ability Questionnaire. DESIGN: Prospective, 1:1 single-blind, randomized, controlled effectiveness study. SETTING: Multicenter study including 156 hospitals and ambulatory surgery facilities. PATIENTS: 2438 patients (1496 outpatients and 942 inpatients) 18 years of age or older, scheduled for elective surgeries under general endotracheal anesthesia, with an expected duration of unconsciousness of > or =30 minutes. INTERVENTIONS: Patients were randomized to receive either intravenous remifentanil (0.5 microg/kg/min for induction and intubation; with the infusion rate decreased to 0.25 microg/kg/min after intubation) or fentanyl (administered according to anesthesiologists' usual practice) as the opioid during surgery. Concomitant hypnotic drugs were propofol and/or isoflurane (with or without nitrous oxide) titrated according to protocol. Transition analgesia with either morphine or fentanyl was given in the remifentanil patients and at the discretion of the anesthesiologists in the fentanyl patients. MEASUREMENTS: A validated set of measurements of functional ability, rather than more traditional clinical psychological methods, to compare the recovery of patients from remifentanil- and fentanyl-treated anesthetic regimens up to 24 hours after surgery. MAIN RESULTS: Remifentanil was statistically superior to fentanyl for the four functional assessments evaluated: walking without dizziness, thinking clearly, concentration, and communicating effectively. These differences reflect events occurring within the first 24 hours after anesthesia and surgery. CONCLUSIONS: A remifentanil-treated anesthetic demonstrated earlier return to some functions than a fentanyl-treated technique. Although functional assessment is a field that is still in its infancy, a questionnaire to assess functional ability during the 24 hours after anesthesia may provide more practical information about anesthetic recovery than previously used, traditional psychomotor evaluations.

A case of tracheal injury after emergent endotracheal intubation: a review of the literature and causalities.

IMPLICATIONS: Tracheal lacerations are rare, but potentially fatal, complications of intubations. Diagnosis of such conditions is difficult, and thus a high level of suspicion must be kept. We present a case and review the literature for factors that indicate high-risk patients.

Duration of action of vecuronium after an intubating dose of rapacuronium, vecuronium, or succinylcholine.

UNLABELLED: Rapacuronium (RAP) is a new, rapid-onset, short-duration, nondepolarizing neuromuscular blocker. If RAP is used to facilitate endotracheal intubation, what will the duration of a subsequent maintenance dose of vecuronium (VEC) be? We investigated the duration of action of a maintenance dose of VEC after intubation with RAP, VEC, or succinylcholine (SUC). Adult surgical patients under general anesthesia were randomly allocated to receive a tracheal intubating dose of RAP 1.5 mg/kg, VEC 0.1 mg/kg, or SUC 1 mg/kg. The anesthetic was induced with propofol and maintained with propofol, nitrous oxide, and oxygen. Neuromuscular function was monitored with electromyography. Recovery of the intubating dose of neuromuscular blocker was allowed to occur spontaneously until the first twitch of the train-of-four (T1) reached 50% of baseline, and then VEC 0.025 mg/kg (0.5 x 95% effective dose [ED(95)]) was administered. The onset, duration, and recovery to T1 = 25% and 50% were recorded. The durations of action (recovery of T1 25%) after intubating doses of RAP, VEC, and SUC were 13.7 +/- 5.3, 43.2 +/- 13.2, and 9.2 +/- 3.7 min (mean +/- SD), respectively (P < 0.0001). The times to maximum depression of T1 after a maintenance dose of VEC (0.5 x ED(95)) were 5.4 +/- 2.9, 5.1 +/- 2.5, and 5.3 +/- 2.8 min (mean +/- SD) for the RAP, VEC, and SUC groups, respectively. Recoveries to T1 25% after VEC for the RAP, VEC, and SUC groups were 18.9 +/- 11.5, 21.5 +/- 8.03, and 12.8 +/- 8.4 min, and at T1 50% they were 21.5 +/- 9.1, 30.8 +/- 9.5, and 15.5 +/- 9.7 min (mean +/- SD), respectively (P < 0.001, RAP and VEC versus SUC). The duration of action of a maintenance dose of VEC was similar after an intubating dose of RAP or VEC but was shortened when preceded by an intubating dose of SUC. IMPLICATIONS: The duration of action of a maintenance dose of vecuronium was longer after an endotracheal intubating dose of rapacuronium compared with succinylcholine.

Assessment of depth of anesthesia and postoperative respiratory recovery after remifentanil- versus alfentanil-based total intravenous anesthesia in patients undergoing ear-nose-throat surgery.

BACKGROUND: The authors investigated whether total intravenous anesthesia (TIVA) with precalculated equipotent infusion schemes for remifentanil and alfentanil would ensure appropriate analgesia and that remifentanil would result in better recovery characteristics. METHODS: Forty consenting patients (classified as American Society of Anesthesiologists physical status I-III) scheduled for microlaryngoscopy were randomized to receive, in a double-blind manner, either remifentanil (loading dose 1 microg/kg; maintenance infusion, 0.25 microg x kg(-1) x min-1) or alfentanil (loading dose, 50 microg/kg; maintenance infusion, 1 microg x kg(-1) x min-1) as the analgesic component of TIVA. They were combined with propofol (loading dose, 2 mg/kg; maintenance infusion, 100 microg x kg(-1) min(-1)). To insure an equal state of anesthesia, the opioids were titrated to maintain heart rate and mean arterial pressure within 20% of baseline, and propofol was titrated to keep the bispectral index (BIS) less than 60. Neuromuscular blockade was achieved with succinylcholine. Drug dosages and the times from cessation of anesthesia to extubation, verbal response, recovery of ventilation, and neuropsychological testing, orientation, and discharge readiness were recorded. RESULTS: Demographics, duration of surgery, and anesthesia were similar between the two groups. Both groups received similar propofol doses. There were no difference in BIS values preoperatively (mean, 96), intraoperatively (mean, 55), and postoperatively (mean, 96). Recovery of BIS and times for verbal response did not differ. At 20, 30, and 40 min after terminating the opioid infusion, the peripheral oxygen saturation and respiratory rate were significantly higher in the remifentanil group compared with the alfentanil group. CONCLUSIONS: When both the hypnotic and analgesic components of a TIVA-based anesthetic are administered in equipotent doses, remifentanil provides a more rapid respiratory recovery, even after brief surgical procedures, compared with alfentanil.

Arm pain as an unusual presentation of postdural puncture intracranial hypotension.

IMPLICATIONS: We report a case of a patient experiencing severe arm pain after dural puncture. This complication has not been reported previously. The patient was successfully treated with an epidural patch.

The use of propofol for its antiemetic effect: a survey of clinical practice in the United States.

STUDY OBJECTIVES: To investigate the use of propofol by anesthesiologists for its antiemetic effect and to compare our findings with published evidence. DESIGN: Anonymous survey of U.S. anesthesiologists. SETTING: American Society of Anesthesiologists' annual meeting. MEASUREMENTS AND MAIN RESULTS: One hundred fifty anesthesiologists were surveyed on how they use propofol to achieve an antiemetic effect. A large majority (84%) of the anesthesiologists surveyed stated they used propofol for its antiemetic effect: 63% of those used propofol for induction only for cases lasting <1 h to achieve an antiemetic effect. In addition 37% used a "sandwich" technique, using propofol at the beginning and end of a case for a similar purpose. There is evidence that the antiemetic effect of propofol is associated with a defined plasma concentration range; mean, 343 ng/mL (10-90% confidence intervals [CI] 200-600 ng/mL). Simulation data demonstrated that after propofol 2 mg/kg, its concentration will drop below 350 ng/mL at 32 min. After 2 mg/kg and 20 mg within 10 min of the end of surgery, its concentration will drop below 350 ng/mL by 7 min after the 20 mg bolus dose. This finding suggests that the plasma concentrations of propofol, when used in these cases, will be below the effective range of antiemetic effect. CONCLUSIONS: Many anesthesiologists used propofol for its antiemetic effect. There is strong evidence for its antiemetic efficacy after anesthesia maintained by a propofol infusion and also for its use in the postanesthesia care unit (PACU). However, there is little evidence to support its use purely at induction of anesthesia or as part of a "sandwich" technique in an attempt to reduce postoperative nausea and vomiting. This is especially true in cases lasting longer than a few minutes.

A preliminary investigation of remifentanil as a labor analgesic.

IMPLICATIONS: In this preliminary investigation, we evaluated the safety and analgesic efficacy of IV remifentanil for labor pain. Four women were studied, and then the trial was terminated because administration of this novel synthetic opioid produced significant maternal side effects in the absence of effective pain control.

Cost-effectiveness of prophylactic antiemetic therapy with ondansetron, droperidol, or placebo.

BACKGROUND: In an era of growing economic constraints on healthcare delivery, anesthesiologists are increasingly expected to understand cost analysis and evaluate clinical practices. Postoperative nausea and vomiting (PONV) are distressing for patients and may increase costs in an ambulatory surgical unit. The authors compared the cost-effectiveness of four prophylactic intravenous regimens for PONV: 4 mg ondansetron, 0.625 mg droperidol, 1.25 mg droperidol, and placebo. METHODS: Adult surgical outpatients at high risk for PONV were studied. Study drugs were administered intravenously within 20 min of induction of nitrous oxide-isoflurane or enflurane anesthesia. A decision-tree analysis was used to group patients into 12 mutually exclusive subgroups based on treatment and outcome. Costs were calculated for the prevention and treatment of PONV. Cost-effectiveness analysis was performed for each group. RESULTS: Two thousand sixty-one patients were enrolled. Efficacy data for study drugs have been previously reported, and the database from that study was used for pharmacoeconomic analysis. The mean-median total cost per patient who received prophylactic treatment with 4 mg ondansetron, 0.625 mg droperidol, 1.25 mg droperidol, and placebo were $112 or $16.44, $109 or $0.63, $104 or $0.51, and $164 or $51.20, respectively (P = 0.001, active treatment groups vs. placebo). The use of a prophylactic antiemetic agent significantly increased patient satisfaction (P < 0.05). Personnel costs in managing PONV and unexpected hospital admission constitute major cost components in our analysis. Exclusion of nursing labor costs from the calculation did not alter the overall conclusions regarding the relative costs of antiemetic therapy. CONCLUSION: The use of prophylactic antiemetic therapy in high-risk ambulatory surgical patients was more effective in preventing PONV and achieved greater patient satisfaction at a lower cost compared with placebo. The use of 1.25 mg droperidol intravenously was associated with greater effectiveness, lower costs, and similar patient satisfaction compared with 0.625 mg droperidol intravenously and 4 mg ondansetron intravenously.

Changes in the auditory evoked potentials and the bispectral index following propofol or propofol and alfentanil.

BACKGROUND: Midlatency auditory evoked potentials (MLAEP) show graded changes with increasing doses of hypnotics but little change with opioids. The effect of their combination on the MLAEP was evaluated. Also, the bispectral index (BIS) was compared with the ability of MLAEP to correlate with sedation and predict loss of consciousness. METHODS: Twenty healthy volunteers were randomly assigned to receive stepped increases in propofol concentration (10 subjects) or propofol plus alfentanil 100 ng/ml (10 subjects). At baseline and at each targeted effect site concentration the mean MLAEP, BIS, measures of sedation, and drug concentration were obtained. The relation among MLAEP, BIS, and sedation score was determined. The prediction probability (Pk) was calculated and compared for BIS and MLAEP. RESULTS: The BIS and MLAEP patterns showed significant changes (Pa and Nb decreased in amplitude and increased in latency) with increasing level of sedation (P < 0.0001). The BIS correlated better with sedation scores (0.884) than did the MLAEP (P < 0.05). Pa and Nb latencies showed the best correlation with sedation levels (0.685 and 0.658, respectively). The addition of alfentanil did not affect the relation between MLAEP and loss of consciousness (P > 0.15). The BIS (Pk = 0.952) was a better predictor of loss of consciousness than were Pa and Nb amplitude (P < 0.05) but were comparable to Pa and Nb latency (Pk = 0.869 and 0. 873, respectively). CONCLUSION: MLAEP changes, like the BIS, correlate well with increasing sedation produced by propofol, and these changes in the MLAEP are independent of the presence of an opioid. Among all the MLAEP parameters, Pa and Nb latencies are the best predictors of increasing sedation and loss of consciousness.

Comparison of remifentanil with alfentanil or suxamethonium following propofol anaesthesia for tracheal intubation.

Sixty ASA physical status I and II, premedicated patients were administered propofol 2 mg x kg-1 and remifentanil 2 microg x kg-1 (group R), alfentanil 50 microg x kg-1 (group A) or suxamethonium 1 mg x kg-1 (group S) as a rapid bolus. One minute after study drug administration, tracheal intubation was performed. Intubation conditions were then scored. Excellent or good conditions were observed in only 35% in group R compared with groups S and A (100% and 85%, respectively; p < 0.001). The haemodynamic response to tracheal intubation was blunted in groups R and A compared with group S (p < 0.001). The mean heart rate in groups R and A was significantly lower than group S (p < 0.001). We conclude that remifentanil 2 microg x kg-1 given as a rapid bolus will not produce intubating conditions as good as those obtained with alfentanil 50 microg x kg-1 or suxamethonium 1 mg x kg-1 if administered after propofol 2 mg x kg-1.

Dosing study of remifentanil and propofol for tracheal intubation without the use of muscle relaxants.

Sixty ASA I and II patients, premedicated with midazolam, were administered propofol 2 mg x kg-1 and remifentanil 3 microg x kg-1 (group R3), remifentanil 4 microg x kg-1 (group R4) and remifentanil 5 microg x kg-1 (group R5). Laryngoscopy and intubation were performed 1 min after the administration of the study drugs and the intubating conditions were assessed. Good to excellent conditions were observed in 12 patients in group R3 compared with 19 patients each in groups R4 and R5 (p = 0.004). Significant reductions in mean arterial pressure (MAP) and heart rate (HR) after administration of the study drug were observed in each group, p < 0.01. There was, however, no difference in mean MAP and HR between the three groups at all time points. We conclude that remifentanil 4-5 microg x kg-1 may reliably provide good to excellent conditions for tracheal intubation when administered after propofol 2 mg x kg-1.

Comparison of the intubation conditions provided by rapacuronium (ORG 9487) or succinylcholine in humans during anesthesia with fentanyl and propofol.

BACKGROUND: Currently, the only approved muscle relaxant with a rapid onset and short duration of action is succinylcholine, a drug with some undesirable effects. Rapacuronium is an investigational nondepolarizing relaxant that also has a rapid onset and short duration and consequently should be compared with succinylcholine in its ability to facilitate rapid tracheal intubation. METHODS: This prospective, randomized clinical trial involved 336 patients. Anesthesia was induced with fentanyl and propofol and either 1.5 mg/kg rapacuronium or 1.0 mg/kg succinylcholine. The goal was to accomplish tracheal intubation by 60 s after administration of the neuromuscular blocking drug. Endotracheal intubation was performed, and conditions were graded by a blinded investigator. Recovery of neuromuscular function was assessed by electromyography. RESULTS: Intubation conditions were evaluated in 236 patients. Intubation by 60 s after drug administration occurred in 100% of patients with rapacuronium and in 98% with succinylcholine. Intubation conditions were excellent or good in 87% of patients with rapacuronium and in 95% with succinylcholine (P < 0.05). The time (median and range) to the first recovery of the train-of-four response was 8.0 (2.8-20.0) min with rapacuronium and 5.7 (1.8-17.7) min with succinylcholine (P < 0.05). The overall incidence of adverse effects was similar with both drugs. CONCLUSIONS: A 1.5-mg/kg dose of rapacuronium effectively facilitates rapid tracheal intubation. It can be considered a valid alternative to 1.0 mg/kg succinylcholine for this purpose.

Determination of the potency of remifentanil compared with alfentanil using ventilatory depression as the measure of opioid effect.

BACKGROUND: Remifentanil is a new opioid with properties similar to other mu-specific agonists. To establish its pharmacologic profile relative to other known opioids, it is important to determine its potency. This study investigated the relative potency of remifentanil compared with alfentanil. METHODS: Thirty young healthy males were administered double-blind remifentanil or alfentanil intravenously for 180 min using a computer-assisted continuous infusion device. Depression of ventilation was assessed by the minute ventilatory response to 7.5% CO2 administered via a "bag in the box" system. The target concentration of the study drug was adjusted to obtain 40-70% depression of baseline minute ventilation. Multiple blood samples were obtained during and following the infusion. The concentration-effect relationship of each drug was modeled, and the concentration needed to provide a 50% depression of ventilation (EC50) was determined. RESULTS: Only 11 subjects in each drug group completed the study; however, there were sufficient data in 28 volunteers to model their EC50 values. The EC50 (mean and 95% confidence interval) for depression of minute ventilation with remifentanil was 1.17 (0.85-1.49) ng/ml and the EC50 for alfentanil was 49.4 (32.4-66.5) ng/ml. CONCLUSION: Based on depression of the minute ventilatory response to 7.5% CO2, remifentanil is approximately 40 (26-65) times more potent than alfentanil when remifentanil and alfentanil whole-blood concentrations are compared. As alfentanil is usually measured as a plasma concentration, remifentanil is approximately 70 (41-104) times more potent than alfentanil when remifentanil whole-blood concentration is compared with alfentanil plasma concentration. This information should be used when performing comparative studies between remifentanil and other opioids.

Patient-controlled antiemesis: a randomized, double-blind comparison of two doses of propofol versus placebo.

BACKGROUND: The role of propofol for the management of postoperative nausea and vomiting (PONV) is not well established. This study determines the efficacy of small doses of propofol administered by patient-controlled device for the treatment of PONV. METHODS: Patients presenting for ambulatory surgery received a standardized general anesthetic. Those who experienced significant nausea or emesis within 1 h of arrival in the recovery room were randomized to receive repeated doses of propofol 20 mg (P-20), propofol 40 mg (P-40), or intralipid (placebo) on demand. Study medications (in equal volumes) were administered with a patient-controlled delivery device for 2 h. A lockout interval of 5 min between doses was used. The following parameters were assessed: nausea, vomiting, rescue antiemetic use, recovery profile, study drug administration history, and satisfaction with treatment. RESULTS: Sixty-nine patients participated in the study. Patient demographics were similar. The average nausea score for a patient in the P-20 and P-40 groups was 25% and 29% less, respectively, compared with placebo during the study period (P < 0.05). This difference was apparent 15 min after initiation of therapy. More placebo patients vomited (P-20, 12%; P-40, 23%; placebo, 56%; P = 0.003) and needed rescue antiemetics (P-20, 17%; P-40, 23%; placebo, 70%; P = 0.001) compared with treatment groups. Sedation scores were similar between groups. Propofol-treated patients had shorter stays in the post-anesthesia care unit (PACU; P-20, 131+/-35 min [mean +/- SD]; P-40, 141+/-34 min; placebo, 191+/-92 min; P = 0.005) and higher satisfaction with their control of PONV than placebo (P < 0.01). CONCLUSIONS: Propofol is effective in managing PONV with shorter PACU stay and great degree of patient satisfaction. There were two episodes of oversedation in the P-40 group. Hence, propofol at a demand dose of 20 mg seems more appropriate.