Reversal of rocuronium-induced neuromuscular block with sugammadex is faster than reversal of cisatracurium-induced block with neostigmine.

BACKGROUND: Reversal of the residual effect of rocuronium or cisatracurium by neostigmine may be slow and associated with side-effects. This randomized, safety-assessor-blinded study compared the efficacy of sugammadex, a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block, with that of neostigmine for reversal of cisatracurium-induced neuromuscular block. The safety of sugammadex and neostigmine was also evaluated. METHODS: Adult surgical patients (ASA class I-III) were randomized to sugammadex 2.0 mg kg(-1) for reversal of block induced by rocuronium 0.6 mg kg(-1), or neostigmine 50 microg kg(-1) for reversal of block induced by cisatracurium 0.15 mg kg(-1). Anaesthesia was induced and maintained using i.v. propofol and remifentanil, fentanyl, or sufentanil. Neuromuscular function was monitored using acceleromyography (TOF-Watch SX). Sugammadex or neostigmine was administered at reappearance of T(2). The primary efficacy variable was time for recovery of the train-of-four (TOF) ratio to 0.9. RESULTS: Eighty-four patients were randomized, 73 of whom received sugammadex (n=34) or neostigmine (n=39). Time from start of administration of reversal agent to recovery of the TOF ratio to 0.9 was 4.7 times faster with sugammadex than with neostigmine (geometric mean=1.9 vs 9.0 min, P<0.0001). Reversal of block was sustained in all patients. There were no serious adverse effects from either reversal agent and no significant changes in any measure of safety, except for similar elevations in urinary N-acetyl glucosaminidase in both groups. CONCLUSIONS: Sugammadex 2.0 mg kg(-1) administered at reappearance of T(2) was significantly faster in reversing rocuronium-induced blockade than neostigmine was in reversing cisatracurium-induced block.

No correlation between remifentanil blood, cerebrospinal fluid and cerebral extracellular fluid levels and TCI prediction: a pharmacokinetic study.

BACKGROUND: The aims of this paper were to elucidate the difference in concentration among remifentanil blood, cerebrospinal fluid and cerebral extracellular fluid levels, and to verify the presumable existence of a correlation between arterial and cerebral remifentanil. We used brain microdialysis to shed light on this aspect of the pharmacokinetic and to correlate these findings with Minto's model. METHODS: The study population was formed by 9 patients scheduled for elective intracranial surgery for cerebral supratentorial neoplasia. All patients received general anaesthetic; 100 microliters of dialysate were collected. Furthermore, arterial blood samples of 3 mL each were collected, respectively one at the beginning and one at the end of the sampling period. We determined the concentration of remifentanil and its main metabolite, remifentanil acid, in the blood and in the brain. The predictive performance of the Minto pharmacokinetic parameter set was evaluated by examining the performance error. RESULTS: The mean Performance Error was -45.13% (min -21.80, max -88.75) for the first series of arterial samples, -38.29% (min -6.57, max -79.17) for the second one and 67.73% (min 7, max -93.12) for the extra cellular fluid sample. The concentration of remifentanil set pumps was correlated with blood concentration for both series of samples. Neither the set concentration, nor the arterial samples were correlated with extra cellular fluid values. CONCLUSION: There was a wide interindividual variability with regard both to blood and cerebral remifentanil concentration. Moreover, the ratio between arterial blood and cerebral remifentanil was not consistent among our patients in spite of a stable infusion rate of remifentanil; at the end we found a trend of over prediction in the ratio between the various compartments examined.

Cardiotoxicity of doxorubicin: effects of 21-aminosteroids.

The purposes of this study were to investigate in vivo the effects of two lazaroids,U-74389G (21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-pregna-1,4,9 (11)-triene-3,20-dione (2)-2-butenenedionate) and U-83836E (-)-2-[[4-(2,6-di-1-pyrrlidinyl-4-pyrimidinyl)-1-piperazinyl]methy l]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol, dihydrochloride against the cardiotoxicity induced by doxorubicin in rat and the mechanisms underlying such a toxicity. Doxorubicin (DXR) administered intraperitoneally (5 mg/kg 4 times per week for 1 week) induced significant decrease of body weight, ECG alterations and 100% mortality. The lazaroids used in this study did not protect from DXR-induced cardiotoxicity. Our results showed that the compound U-74389G delayed, but did not reduce DXR-induced mortality, and did not prevent body weight loss and ECG changes. The compound U-83836E was unable to modify any toxic effects induced by DXR. These data indicate that oxygen free radicals and the subsequent increase in intracellular calcium are only steps of DXR progressive general toxicity that leads to cardiac injury. In conclusion, we propose that the 21-aminosteroids, potent inhibitors of membrane lipid peroxidation, alone are not enough to protect from DXR toxic effects.

Analgesic activity of flupirtine maleate: a controlled double-blind study with diclofenac sodium in orthopaedics.

A controlled, parallel group study of the analgesic efficacy of flupirtine maleate, was compared against diclofenac sodium in 40 orthopaedic patients with post-operative pain. Clinically, both drugs were of equal analgesic efficacy. A mathematical model has been developed, however, to evaluate the speed, intensity and duration of the analgesic effect and provides data which significantly favour flupirtine maleate in the treatment of these patients.

Benzydamine for the prevention of pharyngo-laryngeal pathology following tracheal intubation.

A clinical study was carried out to assess the antiinflammatory effectiveness and related properties of this drug. It was performed double-blind in 40 adult patients (ASA I, and II) undergoing major otorhinolaryngological surgical procedures with tracheal intubation. The patients received benzydamine at random (n = 20), or a similar solution without the active substance (n = 20). The following parameters were considered: physical examination, sensations referred from patient, cytologic examination, glottographic examination, and spectrographic examination. The results suggest that benzydamine applied locally at a concentration of 0.3% has therapeutic efficacy without local or systemic side-effects.

[Prevention of hypertensive crises in the perioperative period. Efficacy and safety of the use of urapidil]. / Prevenzione delle crisi ipertensive durante la fase perioperatoria. Efficacia e sicurezza di impiego di Urapidil.

Hypertension and tachycardia are frequently encountered in the perioperative setting. Aim of this study was to evaluate the efficacy and safety of Urapidil when used for prevention of perioperative blood pressure elevations. 348 patients, at risk for hypertensive crises, were randomly administered either Urapidil or "no treatment". Blood pressure and heart rate were measured the day before as well as immediately before intervention and were continuously monitored during the intraoperative period. This study has shown a pronounced and well tolerated antihypertensive effect of Urapidil during anaesthesia in these patients. The effect on diastolic values was specific for Urapidil, since systolic pressure was lowered also in the control group as a consequence of anaesthesia. Urapidil treatment resulted to be effective in preventing hypertensive reactions following algogenic stimulation. This becomes particularly evident towards the end of the operative period, when the hypotensive effect attributable to the anesthetic itself progressively decreases.

Mechanisms of activation of human mast cells and basophils by general anesthetic drugs.

A study was performed about the effects of increasing concentrations of muscle relaxants (suxamethonium, d-tubocurarine, vecuronium, and atracurium), hypnotics (propofol, ketamine, and thiopental), opioids (morphine, buprenorphine, and fentanyl), and benzodiazepines (diazepam, flunitrazepam, and midazolam) on the release of preformed (histamine and tryptase) and de novo synthesized (prostaglandin D2: PGD2 and peptide-leukotriene C4: LTC4) chemical mediators from human basophils and mast cells isolated from skin (HSMC), lung parenchyma (HLMC) and heart tissue (HHMC). None of the drugs tested induced the release of histamine or LTC4 from basophils of normal donors. Suxamethonium did not induce mediator release from any type of human mast cell tested. Only the highest concentration of d-tubocurarine used caused histamine release from HSMC and HLMC. Atracurium, more than vecuronium, induced concentration-dependent histamine release from HSMC and HLMC. Propofol induced a concentration-dependent histamine release from HLMC, but not from HHMC. Only the highest concentrations of ketamine and thiopental used caused a significant release of histamine from HLMC. The muscle relaxants and hypnotics examined did not induce any de novo synthesis of PGD2 or LTC4 in mast cells. Morphine only induced histamine and tryptase release from HSMC, but not the de novo synthesis of PGD2. In contrast, buprenorphine caused histamine and tryptase release from HLMC, and not from HSMC, whilst it also induced de novo synthesis of PGD2 and LTC4 in HLMC. Fentanyl did not give any histamine and tryptase release from mast cells. Diazepam and flunitrazepam only induced a small release of histamine from mast cells, whereas midazolam caused the release of histamine from HLMC. The biochemical pathways underlying the release of mediators from human mast cells induced by drugs used during general anaesthesia are different from those underlying the immune release of histamine. From the results obtained with the in vitro model described here, it is clear that new drugs promising for the anesthesiologic arena should be tested in vitro before their potential histamine-releasing activity is experienced in vivo.

Do we need to use sugammadex at the end of a general anesthesia to reverse the action of neuromuscular bloking agents? Position Paper on Sugammadex use.

Sugammadex, the first selective relaxant-binding agent indicated to reverse the neuromuscular blockade induced during general anesthesia, was recently introduced into clinical practice. In the present report, the following issues pertinent to the use of sugammadex in anesthesia practice are discussed: the intraoperative use of NMBAs and the incidence of postoperative residual curarization (PORC); the efficacy and safety of rocuronium plus sugammadex compared to succinylcholine for rapid sequence induction; the availability of sugammadex in hospitals; and, finally, some relevant legal medical aspects. Sugammadex is considerably more expensive than neostigmine, but its use can be advocated based on its safety and efficacy profile as a reversal agent of steroidal neuro muscular blocking agents (NMBAs), and as a mean to prevent PORC. The availability of sugammadex in Italian hospitals may have a beneficial impact on patient safety. This is due to the fact that PORC is a common and dangerous condition that may lead to postoperative inhalational events, hypoxemia, and pneumonia; and at the moment, it is not completely preventable even when advanced neuro-muscolar monitoring techniques are applied". In the case of rapid sequence intubation (RSI), rocuronium (1.2 mg/kg) administration followed by sugammadex represents a better choice in terms of efficacy and safety than succinylcholine. If a new drug is proven to be safer and more efficient than the one it is replacing, hospitals should consider the new drug and make it available, at least for selected patients or in situations at risk of severe complications. It is reasonable to hypothesize that, when discussing informed consent for elective procedures, patients and families may want to know if the admitting facilities have the superior agent available, and that the absence of such agent could create concerns and complains.

Cisatracurium versus vecuronium: a comparative, double blind, randomized, multicenter study in adult patients under propofol/fentanyl/N2O anesthesia.

AIM: The aim of this study was to compare the time course characteristics of cisatracurium (C) and vecuronium (V) induced neuromuscular block (NMB) following multiple doses, allowing spontaneous complete recovery (SCRT) and evaluating the influence of age. METHODS: Following institutional approval and signed informed consent, 177 adult ASA 1-2 patients were included in a randomized, double-blind, multicenter study under N20/02/fentanyl/propofol anesthesia. Muscle relaxation was induced with 0.15 mg/kg C or 0.l mg/kg V and was maintained with 0.03 mg/kg of C or 0.02 mg/kg of V injected at T1 25% recovery. Intubating conditions were assessed at 2 min after the initial dose. Time course of NMB was monitored using accelerography (Tofguard) of the adductor pollicis with train-of-four (TOF). Data were analyzed with parametric (Anova) and non parametric statistics (c2, Kruskal Wallis). RESULTS: Both drugs offered good/excellent intubating conditions: duration of action of NMB (mean values +/- SD, minutes) were: dur25 first dose: V 38.20+/-13.2 vs C 51.5+/-11.3 (P<0.02 ); dur25 following repeated boluses (average): V 23.2+/- 8.6 vs C 28.2+/-9.5, ns; dur25 last dose: V 25.1+/-11.5 vs C 31.5+/-11.4, ns: SCRT following last dose: V 50.2+/-23.2 vs C 46.4+/-17.5, ns: t125% to t4/T1 0.80:V 27.1+/-18.7 vs C 18.8+/-10.2, ns. Stratifying for age >or< 65 no differences were noted in the intervals studied following C, while all were longer following V. The duration of block of C was longer than V; the SCRT after the final dose of C was shorter than V albeit not significant. There was a clinically significant increase in duration of block and recovery time in elderly patients for V but not for C. CONCLUSIONS: C and V allow predictable NMB duration and spontaneous recovery even if administered in multiple repeated doses; but in elderly patients duration of block and recovery time is longer following V.

Remifentanil vs fentanyl with a target controlled propofol infusion in patients undergoing craniotomy for supratentorial lesions.

AIM: Remifentanil hydrochloride is an ultra-short acting m-opioid receptor agonist. This study compared the use of remifentanil with that of fentanyl during elective supratentorial craniotomy in a target controlled infusion (TCI)-propofol anesthesia regimen and evaluated the quality of recovery from anesthesia. METHODS: After written informed consent for this prospective study, 40 adult patients were randomly divided into 2 groups: in group F analgesia was provided with fentanyl 2-3 mg kg(-1) h(-1) and in group R with remifentanil 0.25 mg kg(-1) h(-1). Anesthesia was induced with thiopental and pancuronium bromide, and maintained with propofol-TCI, pancuronium, air and oxygen and fentanyl (group F) or remifentanil (group R), respectively. After tracheal intubation, infusion rate of remifentanil was reduced and then adjusted to maintain stable hemodynamics. Hemodynamics and recovery time were monitored for 60 min after surgery. Analgesic requirements, propofol intraoperative consumption, nausea and vomiting in postoperative period were monitored. Recovery was evaluated according to a modified Aldrete score. RESULTS: Baseline hemodynamics were similar in both groups. Mean arterial pressure differed between the 2 groups (P<0.05) with the greatest decrease in group R during dura opening (P<0.001). Postoperative mean arterial pressure was higher in group R. Patients in group R exhibited a faster recovery. The incidence of nausea and vomiting was similar in the 2 groups. Noteworthy, there was a reduction in the amount of propofol used in group R. CONCLUSIONS: Remifentanil appears to be a reasonable alternative to fentanyl during elective surgery of supratentorial lesions.

[Sufentanyl in balanced anesthesia for neurosurgery. Comparative study with fentanyl] . / Il sufentanil nell'anestesia bilanciata in neurochirurgia. Studio comparativo con il fentanyl.

BACKGROUND: The aim of this study was to evaluate the effects of sufentanil in comparison with those of fentanyl during balanced anesthesia in patients undergoing neurosurgery. EXPERIMENTAL DESIGN: prospective randomized study. SETTING: operating room in a neurosurgery University department. PATIENTS: 50 patients, ASA I and II with age ranging from 18 to 77 years were divided in two groups randomly. INTERVENTIONS: 25 patients received sufentanil as single bolus dose of 0.2 microgram/kg i.v. as premedication and supplemental bolus doses of 0.15 microgram/kg during the maintenance of anesthesia while the remainders received fentanyl 2.0 micrograms/kg as premedication and supplemental boluses of 1.5 micrograms/kg. All patients were induced with propofol 2.5 mg/kg, were intubated after cisatracurium 0.15 mg/kg for muscle relaxation, then were ventilated with sevoflurane and O2:N2O (1:1). MEASUREMENTS: heart rate, SAP, DAP and MAP were recorded at different times and ECG, ETCO2 and pulsoximetry were monitored continuously. Furthermore postoperative analgesia by VAS, recovery time and inspiratory concentrations of the volatile anesthetic were evaluated. Statistical analysis was carried out using ANOVA for repeated measures and Bonferroni "t"-test; a value of p < 0.05 was considered to be significant. RESULTS: Significant changes in MAP (at IOT and 1 and 2 min after IOT), in HR (at IOT) and in RPP (at IOT and 1, 2 and 3 min after IOT) were recorded in group F. Recovery time was shorter in group S than in group F and postoperative analgesia was more prolonged in group S. Inspiratory concentrations of volatile agent were lower in patients treated with sufentanil than in those treated with fentanyl. CONCLUSIONS: In patients treated with sufentanil a better cardiocirculatory stability was achieved with lower inspiratory concentrations of volatile agent and a well relaxed brain. Sufentanil can be considered a valid alternative to fentanyl as analgesic agent in balanced anesthesia for neurosurgery.

Observational study on the use of remifentanil in general anesthesia. Drug utilisation research.

AIM: The use of remifentanil in routine clinical practice during the induction and maintenance of general anesthesia as well as the quality of awakening after anesthesia and post-operative pain management have been assessed. METHODS: A total of 123 Italian anesthetists were involved; data of 1 295 patients (ASA I-IV) undergoing surgical interventions (range duration of intervention 30-240 min), in which remifentanil was used according to internal anesthesiologic procedures, have been collected. The most common modality of anesthesia induction is to use a syringe pump to start remifentanil administration. The remifentanil dosage mainly used to start the infusion was 0.2 mg/kg/min (29.2% of patients), as well as at the beginning of maintenance of anesthesia (35.1%). RESULTS: During maintenance of anesthesia, 36% of surgical interventions did not need changes of remifentanil infusion rate, whereas in the rest of the intervention 1 to 4 changes were done. The induction of anesthesia is predominantly intravenous with concomitant use of propofol and TPS, whereas the agents most frequently used during maintenance were sevoflurane (49.8%), nitrous oxide (43.7%) and propofol (35.2%). Awakening was mainly judged rapid in 93% of interventions; the postoperative pain at awakening was judged nil in 61% of cases and severe in 1.5%. The administration of analgesic treatment mainly started prior to the end of intervention (70% cases). CONCLUSION: This Drug Utilisation Research study demonstrated that the use of remifentanil according to its peculiar pharmacological profile, such as potent opioid with rapid onset and offset of action, the synergistic effect with propofol and the right management of post-operative pain are widely consolidated in Italian clinical practice.

Rational use of opioids.

The role of analgesia and sedation in intensive care units (ICU) is ancillary to other intensive care strategies, nevertheless they permit that every other diagnostic and therapeutic procedure is safely performed by keeping the patient pain-free, anxiety-free and cooperative. Commonly used opioids in ICU include morphine, fentanyl, sufentanil and remifentanil. The choice among opioid drugs relies on their pharmacokinetics and their pharmacodynamic effects. Cardiovascular stability observed with fentanyl and sufentanil indicates their use in hemodynamically compromised patients. Short-acting remifentanil offers several advantages in patients requiring prolonged infusions. The organ-independent metabolism of this newer molecule may be valuable in patients with multiple organ failure. The main indications for opioid analgesia and sedation in ICU include: 1) Anxiety, pain and agitation: in turn, they can increase cardiac workload, myocardial oxygen consumption and rate of dysarrhythmias; 2) immediate postoperative period after major surgery; 3) short-term invasive procedures. Potential advantages offered by opioids in the ICU setting also include: a) Cardiac protection: in animal models, it has been observed that delta-opiate receptor stimulation confers a preconditioning-like protective effects against myocardial ischemia; b) Neuroprotection: recent studies suggest that mu- and kappa-opiate receptors are involved in ischemic preconditioning against seizures in the brain. During opioid therapy in the ICU, drug tolerance and withdrawal symptoms should be anticipated and the dose adjusted accordingly.

Analgesic transition after remifentanil-based anesthesia in neurosurgery. A comparison of sufentanil and tramadol.

AIM: Transition from the end of remifentanil infusion and postoperative analgesia must be planned carefully owing to remifentanil's (R) rapid offset. Intraoperative morphine has been used for the transition to postoperative analgesia following remifentanil-based anesthesia. Sufentanil (S) is a very potent opioid with high micro-receptor affinity, a much wider therapeutic index and a lower fractional receptor occupancy. These pharmacological and dynamics features make sufentanil an interesting alternative to morphine for immediate postoperative analgesia. EXPERIMENTAL DESIGN: perspective, randomized, single blinded and comparative study. Institution: neurosurgical operating theatre at University. PATIENTS: 96 patients, aging from 25 to 67 years, ASA class I-III, undergoing neurosurgical operations, were studied. INTERVENTIONS AND MEASUREMENTS: the anesthetic management was: premedication: atropine 0.01 microg kg(-1) + remifentanil 0.20 microg kg(-1) min(-1); induction: propofol 2.0 microg kg(-1) + cisatracurium 0.15 microg kg(-1); maintenance: sevoflurane 0.8% + remifentanil (titrated infusion) cisatracurium. All patients received ketorolac 30 mg i.v. 1 hour before the end of surgery and ketorolac (60-90 mg) + tramadol (200-300 mg) by elastomeric pump; patients were divided into 2 groups: group T receiving tramadol 100 mg and group S receiving a bolus dose of sufentanil 0.10 microg kg(-1), 30 and 15 minutes before the end of surgery respectively. Recovery time, postoperative analgesia evaluated by VAS, cardiocirculatory parameters and side effects like nausea, vomiting, shivering, muscle rigidity, sedation and respiratory depression were recorded. RESULTS: VAS was significantly lower in Group S. Recovery time was shorter in Group T than in Group S (8.8 +/- 3.6 vs 11.6 +/- 4.6 min), no statistically significant differences between groups as regards nausea, vomiting and shivering. Short-lasting respiratory depression was detected in 3 cases in Group S. CONCLUSION: At the emergence much better control of the transition phase in patients treated with sufentanil: smooth recovery with better tolerability of the endotracheal tube; efficacious analgesia along with cardiocirculatory stability.

[The effects of remifentanil on hemodynamic response to intubation. A comparative study with fentanyl] . / Gli effetti del remifentanil sulla risposta emodinamica all'intubazione. Studio comparativo con il fentanyl.

BACKGROUND: The aim of this study was to evaluate the effects of remifentanil in comparison with those of fentanyl on the hemodynamic response to orotracheal intubation. EXPERIMENTAL DESIGN: prospective comparative and randomized study. SETTING: operating room in a neurosurgery department at University. PATIENTS: 50 patients, ASA I or II with age ranging from 32 to 64 years were divided in two groups randomly. INTERVENTIONS: 25 patients received fentanyl as single bolus dose of 2.0 micrograms/kg and atropine 0.01 mg/kg i.v. as premedication while the remainders received atropine 0.01 mg/kg i.v. and remifentanil 0.2 microgram/kg/min as infusion. All patients were induced with propofol 2.0 mg/kg and cisatracurium 0.15 mg/kg for muscle relaxation and were intubated 4 min after induction of anesthesia. MEASUREMENTS: Heart rate, SAP, DAP, MAP and RPP were recorded at different times: baseline, induction, intubation, 1, 2, 3 and 4 min after intubation; ECG and pulsoximetry were monitored continuously. Statistical analysis was carried out using ANOVA for repeated measures and Bonferroni t-test a value of p < 0.05 was considered to be significant. RESULTS: Significant increases in PAS were recorded, at intubation and at 1 min after in patients treated with fentanyl; in the remifentanil group significant decreases in SAP at induction and at 4 min after intubation were recorded. HR increased significantly at intubation and at 1, 2 and 3 min after in the fentanyl group. RPP showed a significant decrease at induction in the remifentanil group and significant increases at intubation and at 1, 2 and 3 min after in patients treated with fentanyl. CONCLUSION: In conclusion remifentanil was found to properly control the hemodynamic response to intubation in comparison with fentanyl.

[Tracheal intubation in a case of idiopathic pulmonary fibrosis using remifentanil and propofol without muscle relaxants]. / Intubazione tracheale in un paziente con fibrosi polmonare idiopatica previa somministrazione di remifentanil e propofol senza l'uso di miorilassanti.

The anesthetic management of a 58 year-old-male suffering from idiopathic pulmonary fibrosis associated with a previous experience of altered dose-response relationship to muscle relaxants is reported. He underwent a gastroendoscopic surgical procedure. After intravenous atropine, remifentanil 3.0 microg kg(-1) was injected over 90 sec. Sixty seconds after the start of remifentanil bolus dose, propofol 2.0 mg kg(-1) was injected and intubation was performed 1 min after the administration of propofol. Anesthesia was maintained by N(2)O, oxygen, sevoflurane (0.5-0.8%) and remifentanil titrated infusion (mean dose of 0.15 mg kg(-1) min(-1)) under spontaneous respiration or assisted ventilation, if the patient was apnoic. The intubating conditions were good, a 30 per cent reduction in MAP was observed after propofol administration. The patient regained consciousness 5 minutes after the end of remifentanil administration and his trachea was extubated without any troubles. Recovery was uneventful without the need of long-term intensive therapy.

[Remifentanil in anesthesia and intensive care]. / Remifentanil: una realtà dall'anestesia alla terapia intensiva.

Remifentanil (R) is a novel short-acting mu-receptor opioid. R is in the same structural family as fentanyl and the other phenylpiperidines, but it differs from fentanyl because of its pharmacokinetic profile and its metabolism: R undergoes extrahepatic metabolism by blood and tissue nonspecific esterases. For these reasons the time required for decreases of any percentage plasmatic concentrations of R after termination of the infusion is independent of infusion duration. The pharmacokinetic profile of R is organ-independent and the dosing regimen must be regulated in elderly patients by reducing the bolus and infusion doses, and in obese subjects by calculating the intravenous dosages as a function of age and lean body mass. The placental transfer of R doesn't affect the newborn as recently described in literature but further and wider clinical experiences are needed for assessing the use of R in obstetric anesthesia. R causes either a reduction in the MAC of volatile anesthetics or a decrease in propofol requirements but it cannot be used as a sole anesthetic agent. R can be utilized to facilitate tracheal intubation without using muscle relaxants, to manage analgesia and sedation also in association with midazolam and/or propofol, furthermore as analgesic agent for monitored anesthesia care, for the critical patient in ICU and for the postoperative analgesia if a proper analgesic strategy had not been planned.