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PubMed2006

Comparison of the EEG-based SNAP index and the Bispectral (BIS) index during sevoflurane-nitrous oxide anaesthesia.

The BIS monitor (Aspect Medical Inc, Newton, USA) was the first electroencephalogram (EEG)-based monitor of the hypnotic effect reflected by a dimensionless figure ranging from 100 (awake state) to 0 (flat line EEG). Its widespread use makes it the most-studied and the best-known among same intended devices. Its algorithm processes low-frequency EEG oscillations in order to provide the Bispectral index. A BIS index ranging from 40 to 60 has been established as the proper for surgical performance. The BIS monitor permits a closer approach to the hypnotic component of anaesthesia beyond clinical signs and may reduce the probability of intraoperative awareness; therefore, it has become a recommended monitoring tool in routine practice. The SNAP monitor (Nicolet Biomedical, Madison WI, USA) is also intended for monitoring the hypnotic effect of anaesthetics, which is in turn displayed as an index ranging from 100 to 0, with 100 meaning a fully awake state and 0 meaning no brain activity. The algorithm of the SNAP monitor is featured by its additional processing of ultra-high EEG frequencies, which seem to be involved in the formation of consciousness. The use of these frequencies would theoretically improve responsiveness during increased brain activity. We studied its behaviour patterns and capability to monitor the hypnotic effect induced by sevoflurane-nitrous oxide by comparison with the BIS index. Seventy patients ASA I-III were induced with propofol, fentanyl and rocuronium, and maintained with sevoflurane-N(2)O. BIS and SNAP indices were simultaneously recorded before induction, after intubation, after incision, at the following 10, 30 and 50 minutes, awakening and extubation time points, together with heart rate and blood pressure. The Pearson correlation was R(2) = 0.68 (p < .05). The Bland and Altman test showed a bias of 14.3 for SNAP index values with respect to BIS index values. We concluded that the SNAP index correlates with variations in the hypnotic effect induced by sevoflurane-nitrous oxide anaesthesia when compared with the BIS index. In this context, a SNAP index ranging from 58 to 70 would be equivalent to the BIS index range 40 to 60 and, therefore, the accurate for surgical performance.

Adult↗
PubMed2004

[Protocol for advanced prehospital emergency care of severe head injury].

OBJECTIVES: To analyze the frequency of systemic factors leading to secondary brain insults in victims of serious head trauma in a prehospital setting and to evaluate a protocol for the advanced prehospital emergency care by mobile intensive care unit (i.e., the French Samu-Smur system). STUDY DESIGN: Prospective study, over a period of 24 months. PATIENTS AND METHODS: This prospective study involved 60 victims of severe head injuries (with the exception of polytrauma patients). Tracheal intubation was performed on each patient under direct laryngoscopy and after induction of anaesthesia (fentanyl-etomidate-rocuronium). Controlled ventilation and vascular loading (objectives: SpO(2) >or= 97%, PETCO(2) between 30 and 35 mmHg, SAP >or= 90 mmHg) were administered. RESULTS: Hypoxaemia was found to be the most frequent cause of secondary insults (57% of patients with SpO(2) < 97%). In the case involving an accident that occurred 17 km from the hospital (with extremes of 6-65 km), the speed of medical intervention was note-worthy: tracheal intubation was performed 50 min after the accident, and the patient was admitted into a trauma centre 101 min after impact (median). However, faster intervention could be obtained if the transmission of the alert was improved. The conditions under which the tracheal intubation was performed were found to be satisfactory (difficult intubation 1.6%) without deteriorating the haemodynamic status. This is probably related to the use of muscle relaxants and the choice of etomidate as the first line hypnotic in the prehospital emergency care.

Adolescent↗
PubMed2004

[Anaphylactic and anaphylactoid reactions occurring during anaesthesia in France. Seventh epidemiologic survey (January 2001-December 2002)].

OBJECTIVES: Hypersensitivity reactions IgE-mediated (anaphylaxis) or non-IgE-mediated (anaphylactoid) reactions occurring during anaesthesia remain a major cause of concern for anaesthesiologists, since these reactions remain usually unpredictable, may be potentially life-threatening even when appropriately treated. The authors report the results of the last 2-year survey (2001, 2002) of such reactions conducted in France by the GERAP (groupe d'etude des reactions anaphylactoides peranesthesiques), and compare these results with their previous published surveys. METHODS: Between January 1, 2001 to December 31, 2002, 712 patients who experienced immune-mediated (anaphylaxis) or non-immune-mediated (anaphylactoid) reactions were referred to one of the 40 allergo-anaesthesia centres members of the GERAP. Anaphylaxis was diagnosed on the basis of clinical history, tryptase measurements during the adverse reaction, and skin tests and/or specific IgE assay. RESULTS: Anaphylactic and anaphylactoid reactions were diagnosed in 491 cases (69%) and 221 cases (31%), respectively. The most common causes of anaphylaxis were neuromuscular blocking agents (NMBA) (n=271, 55%), latex (n=112, 22.3%), and antibiotics (n=74, 14.7%). Succinylcholine (n=102, 37.6%) and rocuronium (n=71, 26.2%) were the most frequently incriminated NMBAs. Cross-reactivity between NMBAs was observed in 63.4 % of cases of anaphylaxis to a NMBA. No difference was observed between anaphylactoid and anaphylactic reactions when the incidences of atopy, food, or drug intolerance were compared. However atopy, asthma and food allergy were significantly more frequent in case of latex allergy, when compared with NMBA allergy. Clinical manifestations were more severe in anaphylaxis. The positive predictive value of tryptase measurement for the diagnosis of anaphylaxis was 95.3%, the negative predictive value 49%. The diagnostic value of specific neuromuscular blocking agent IgE assays was confirmed. CONCLUSION: Our results further corroborate the need for systematic screening in case of immediate hypersensitivity reaction during anaesthesia and for the constitution of allergo-anaesthesia centres to provide expert advice to anaesthesiologists and allergologists.

Adolescent↗
PubMed2005

Anaesthetic management during labour of a manifesting carrier of Duchenne muscular dystrophy.

We describe the peripartum anaesthetic management of a 36-year-old woman who was a manifesting carrier of Duchenne muscular dystrophy. Duchenne muscular dystrophy is an X-linked recessive disorder affecting young males associated with severe complications during anaesthesia if depolarising neuromuscular blocking drugs and volatile agents are used. A manifesting carrier is a heterozygous female who demonstrates the disease in a milder form than in males. This probably occurs because of skewed X-inactivation. We planned to establish regional anaesthesia should an operation be necessary during labour or delivery and to use propofol total intravenous anaesthesia and rocuronium if general anaesthesia became unavoidable. At 37 weeks, the woman went into spontaneous labour, but fetal distress necessitated caesarean section for which combined spinal-epidural anaesthesia was used.

Adult↗
PubMed2004

The effects of remifentanil and alfentanil-based total intravenous anesthesia (TIVA) on the endocrine response to abdominal hysterectomy.

STUDY OBJECTIVE: To compare the effects of remifentanil with alfentanil as a part of total intravenous anesthesia (TIVA) on plasma concentrations of cortisol, insulin, and glucose, and hemodynamic responses in patients undergoing abdominal hysterectomy. DESIGN: Randomized, double-blind study. SETTING: University hospital. PATIENTS: 24 ASA physical status I female patients scheduled for abdominal hysterectomy. INTERVENTIONS: Premedicated patients were randomly allocated to receive either remifentanil-propofol (Group R) or alfentanil-propofol (Group A). The loading dose of the study drug was administered over 60 seconds (remifentanil l microg kg(-l) or alfentanil 10 microg kg(-l)) followed by a continuous infusion (remifentanil 0.2 microg kg(-l) min(-l) or alfentanil 0.5 microg kg(-l) min(-l)). In both groups, propofol was administered until loss of consciousness and maintained with a propofol infusion rate of 100 microg kg(-l) min(-l). After induction of anesthesia, all patients were manually ventilated by mask with O2-air mixture for 20 minutes. Then rocuronium 0.6 mg kg(-l) was given for tracheal intubation. MEASUREMENTS: Mean arterial pressure (MAP) and heart rate (HR) were recorded. Plasma concentrations of cortisol, insulin, and glucose were measured during anesthesia and in the recovery room. MAIN RESULTS: In Group R, MAP and HR were lower after tracheal intubation and skin incision than in Group A (p < 0.05). Plasma cortisol concentrations decreased from baseline values at 20 minutes after induction, after tracheal intubation, and skin incision in Group R (p < 0.001). Plasma concentrations of cortisol and glucose increased from baseline values at 30 minutes after skin incision and continued to increase in both groups (p = 0.001). Plasma concentrations of cortisol, insulin, and glucose did not differ between groups at all sampling times. CONCLUSION: Remifentanil provided better hemodynamic stability than alfentanil during anesthesia and surgery. However, both remifentanil and alfentanil had similar effects on the stress endocrine response to abdominal hysterectomy.

Adult↗
PubMed2005

Recovery and cognitive function after fentanyl or remifentanil administration for carotid endarterectomy.

STUDY OBJECTIVE: To compare recovery and restoration of cognitive function after fentanyl-propofol or remifentanil-propofol anesthesia administration in patients undergoing carotid endarterectomy. DESIGN: Randomized, double-blind, prospective study. SETTING: Department of Anesthesiology, University hospital. PATIENTS: Seventy patients with ASA physical statuses II and III (53 men and 17 women) undergoing elective carotid endarterectomy. INTERVENTIONS: Anesthetic technique and drugs were identical in the 2 groups, with the exception of remifentanil and fentanyl administration. Induction of anesthesia was obtained with a bolus dose of propofol (1-2 mg/kg), maintenance was achieved with a propofol infusion according to hemodynamics and nitrous oxide/oxygen (FIO(2), 0.50). Muscle relaxation was achieved with rocuronium. The remifentanil group received 1 microg/kg of remifentanil as a single dose during the induction of anesthesia and 0.5 microg/kg per minute as an infusion throughout the procedure. The fentanyl group received 2 microg/kg of fentanyl as a single dose during the induction of anesthesia. MEASUREMENTS: Intraoperative hemodynamic adverse events were recorded. All patients were also evaluated with regard to their recovery and the restoration of their cognitive function, recording the immediate recovery times and using the Aldrete score 15 and 60 minutes after surgery and the Hasegawa scale 6 hours after surgery. For evaluation of postoperative pain, the Numeric Pain Scale (0-10) was used. MAIN RESULTS: Patients receiving remifentanil had significantly (P < .05) fewer episodes of intraoperative hypertension and needed nitroglycerine administration less frequently (P < .05) than those receiving fentanyl. Immediate recovery was significantly earlier (P < .05) with remifentanil (eye opening, 5.1 +/- 1.3 [remifentanil] and 7.2 +/- 3.7 [fentanyl] minutes; extubation time, 5.4 +/- 1.9 [remifentanil] and 7.8 +/- 4.1 [fentanyl] minutes). The Hasegawa Dementia Scale scores 6 hours after surgery and Aldrete scores 15 and 60 minutes after surgery did not differ significantly between the 2 groups. Pain levels were also similar for patients taking remifentanil and fentanyl. CONCLUSIONS: Although intraoperative hemodynamics were better preserved and immediate recovery was more rapid with remifentanil, overall postoperative recovery and restoration of cognitive functions as well as postoperative pain intensity seem to be similar for patients receiving remifentanil and for those receiving fentanyl combined with propofol for carotid endarterectomy operations.

Aged↗
PubMed2005

Anesthesia with 1.5 minimum alveolar concentration sevoflurane is not altered by physostigmine as measured by bispectral and clinical indices.

STUDY OBJECTIVE: To evaluate the effect of physostigmine on 1.5% sevoflurane anesthesia and recovery. DESIGN: Prospective, randomized, double-blinded study. SETTING: Operating room of a university-affiliated, metropolitan hospital (Aretaieion Hospital and St Savas Hospital). PATIENTS: Forty female American Society of Anesthesiologists physical status I and II patients scheduled for breast biopsy. INTERVENTIONS: Patients were randomly assigned in physostigmine (PHYSO) and normal-saline (NS) group. Anesthesia was induced with sevoflurane 8% using a vital capacity breath technique, and rocuronium 0.6 mg/kg was given to facilitate Laryngeal Mask Airway (LMA) No. 4 insertion. Anesthesia was maintained with end-tidal sevoflurane 1.5 minimum alveolar concentration (MAC; 3% end-tidal concentration) throughout the procedure. MEASUREMENTS: After skin closure and under steady-state sevoflurane anesthesia 1.5 MAC, heart rate, blood pressure, and Bispectral Index (BIS) were recorded. Immediately after, the PHYSO group received intravenous 2 mg of physostigmine, whereas the NS group received equal volume of normal saline. Bispectral Index and hemodynamic measurements were recorded 5, 8, and 10 minutes after treatment. Anesthesia was then discontinued and the LMA was removed. Zero, 15, and 30 minutes after LMA removal, patients were evaluated for orientation, sedation, sitting ability, and the "picking up matches" test, as well as for nausea and vomiting. MAIN RESULTS: No difference was found in BIS (29 +/- 4, 32 +/- 6, 31 +/- 6, 30 +/- 7, 84 +/- 11 in the PHYSO group vs 29 +/- 6, 30 +/- 6, 30 +/- 5, 31 +/- 5, 86 +/- 7 in the NS group), hemodynamic parameters, or recovery parameters between the 2 groups at any time. No nausea or vomiting was observed in either group. CONCLUSIONS: Physostigmine did not influence BIS values or early recovery when administered to patients anesthetized with 1.5 MAC sevoflurane anesthesia.

Adult↗
PubMed2006

Quaternary derivatives of granatanol diesters: potent, ultrashort acting non-depolarizing neuromuscular relaxants.

The purpose of this study was to explore the feasibility of utilizing the granatanol: N-methyl [9-azabicyclo (3.3.1) nonane] 3-alpha-ol as the terminal group in a series of new bisquaternary azabicycyclic diester-type neuromuscular blocking agents. Fifty two bisquaternary ammonium derivatives of several dicarboxylic acid esters of granatanol and three similar derivatives of pseudo granatanol have been investigated for neuromuscular blocking (NMB) potency (ED(50) s), onset and recovery of action and for cardiovascular side effects. All agents were studied first in anesthetized rats, and selected agents were subjected to further pharmacodynamic testing in rabbits, juvenile pigs, cats, dogs and monkeys. One agent was tested in continuous i.v. infusion mode in comparison with its corresponding tropine diester and the aminosteroid muscle relaxant, rocuronium. Several new and highly potent NMB granatanol derivatives are described, which are largely similar in NMB potency to the previously described tropine: N-methyl [8-azabicyclo (3.2.1)] 3-alpha-ol diester derivatives. The majority of the presently described granatanol derivatives displayed ultrashort onset and duration of actions. In that respect some of these agents proved to be the fastest and shortest acting non-depolarizing muscle relaxants described so far. On the negative side, many, but not all, granatanol derivatives produced cardiovascular side effects: e.g. changes in heart rate and blood pressure. Like with the similar tropinyl diester derivatives, cardiac vagal block was present with the majority of these agents as assessed in the rat, pig and cat. Few glutaryl, fumaryl and cyclobutane (trans) 1,2-dicarboxylyl granatanol diesters quaternized with disubstituted benzyl halides, bearing p-acyloxy radicals, showed excellent NMB profile. In these derivatives, however, the rapid decomposition of the p-acyloxy groups leads to formation of toxic quinone methene metabolites which precludes their further pharmaceutical development. The pseudo granatanol derivatives were less potent in the rat than the corresponding granatanols and were not further investigated. We conclude that the 9-azabicyclo (3.3.1) nonane (granatane) ring system can successfully replace the similar 8-azabicyclo (3.2.1) octane (tropane) ring system in building potent, utrashort acting NMB agents.

Animals↗
PubMed2003

Propofol anesthesia in children does not induce sister chromatid exchanges in lymphocytes.

BACKGROUND: Propofol is frequently used for general anesthesia in children although little is known about possible genotoxic effects in humans. We investigated the formation of sister chromatid exchanges (SCE) in metaphase chromosomes of T-lymphocytes of children as a marker for possible genotoxocity following total intravenous anesthesia with propofol for minor surgical procedures. METHODS: 40 children ASA classification I-III were included (ASA I n=34, ASA II n=5, ASA III n=1) in the study. Anesthesia was induced by propofol (3mg/kg) and alfentanil. Succinylcholine or rocuronium were administered for muscle relaxation. After tracheal intubation anesthesia was maintained by continuous propofol infusion at 12 mg/(kgh). Blood samples were drawn before induction and after termination of anesthesia. Following a 72 h cell culture period, 25 T-lymphocyte metaphases per blood sample for all children were analyzed for SCE frequencies. RESULTS: Total intravenous anesthesia with propofol on children did not influence SCE rates in metaphase chromosomes of T-lymphocytes. No SCE differences could be detected between blood samples before initiation and after termination of anesthesia (Wilcoxon signed rank test). Slightly elevated SCE rates were obtained in T-lymphocytes of girls compared to boys, but these differences did not reach statistical significance. CONCLUSIONS: Propofol anesthesia under the chosen conditions did not induce the formation of SCE in children in vivo. No genotoxic effect of a short term exposure to propofol during pediatric anesthesia had been observed.

Adolescent↗
PubMed2002

Functional characterization of the mouse organic-anion-transporting polypeptide 2.

We have isolated and functionally characterized an additional murine member of the organic-anion-transporting polypeptide (Oatp) family of membrane transport proteins from mouse liver. The 3.6 kb cDNA insert contains an open reading frame of 2010 bp coding for a 670 amino acid protein. Based on its amino acid identity of 88% to the rat Oatp2, it is considered the mouse Oatp2 orthologue. Functional expression in Xenopus laevis oocytes demonstrated that mouse Oatp2 transports several general Oatp substrates such as estrone-3-sulfate, dehydroepiandrosterone sulfate (DHEAS), ouabain and BQ-123 but hardly any taurocholate nor rocuronium or deltorphin II. The high-affinity rat Oatp2 substrate digoxin is transported with a rather low affinity with an apparent K(m) value of 5.7 microM. Bromosulfophthalein (BSP), a substrate not transported by the rat Oatp2, is transported very well by mouse Oatp2. Northern blot analysis demonstrated a predominant expression in the liver with additional signals in kidney and brain. Using fluorescence in situ hybridization, the Oatp2 gene (gene symbol Slc21a5) was mapped to chromosome 6G1-G3.

Amino Acid Sequence↗
PubMed1999

Prevention of hypotension after induction of anesthesia after preoperative tune-up. A preliminary report of the Groningen Tune-up Study.

OBJECTIVE: To investigate whether the frequently occurring hypotension after induction of anesthesia can be prevented by preoperative treatment at the ICU guided by hemodynamic data obtained from a pulmonary artery (PA) catheter. DESIGN: Prospective controlled open randomized single center study. SETTING: University tertiary referral hospital. PATIENTS: Thirty-one patients undergoing major vascular- or abdominal surgery. INTERVENTIONS: Patients were randomized to either the control group or the ICU group. Patients allocated for the ICU group were admitted to the ICU the day before the operation and treatment was started aimed at a CI > or = 4.0 l/min/m2. No special treatment was given to the control group the day before the operation. Anesthesia was induced with etomidate, rocuronium and sufentanil. MEASUREMENTS AND MAIN RESULTS: Seventeen patients were allocated for the control group and 14 for the ICU-group. Mean ages were 65 +/- 2.5 and 66 +/- 2.5 years, respectively. Both groups were comparable regarding age, sex, blood pressure and type of operation. Filling pressures at admission on the ICU were: central venous pressure 3 +/- 2 mm Hg and pulmonary capillary wedge pressure 8 +/- 3 mm Hg while CI was 3.2 +/- 0.8 l/min/m2. The hemodynamic goal was achieved in all 14 patients of the ICU-group preoperatively with a background infusion of three l/24 h crystalloids, after a mean infusion of 1623 +/- 552 ml colloids, and in seven patients a median dose of 3 micrograms/kg/min (range 2-6) dopamine. Blood pressure before induction was comparable in both groups. The fall in systolic BP 10 min after induction of anesthesia was 22 +/- 18 in the ICU-group versus 41 +/- 17 mm Hg in the control group (p = 0.004). The fall in diastolic BP was 11 +/- 6 mm Hg in the ICU group versus 25 +/- 11 mm Hg in the control group (p = 0.0003). No differences between the groups in changes of heart rate were observed: a decrease of 13 +/- 7 bpm (95% confidence intervals 8.5 to 17.0) in the ICU group versus 15 +/- 14 (95% confidence intervals 7.6 to 21.9) bpm in the control group (p = 0.6). CONCLUSIONS: Hypotension after induction of anesthesia is significantly attenuated by preoperative treatment aiming at a CI > or = 4.0 l/min/m2 in high risk patients planned for major vascular- or abdominal surgery.

Aged↗
PubMed1999

[Epidemiology of anesthetic anaphylactoid reactions. Fourth multicenter survey (July 1994-December 1996)].

Since 1984 an epidemiological survey of anaphylactoid reactions occurring during anaesthesia has been obtained in France with regular repeated inquiries by the Perioperative Anaphylactoid Reactions Study Group (Gerap). The members of this group collected during the study period cases of patients having suffered from an anaphylactoid reaction and subsequently tested in their allergoanaesthetic outpatient clinic. The three previous surveys published in the Annales françaises d'anesthésie et de réanimation in 1990, 1993 (in English) and 1996 included 1,240, 1,585 and 1,730 patients respectively. The current survey concerned 1,648 patients, tested by the GERAP (38 diagnostic centres) from July 1994 to December 1996. The diagnostic tests for IgE anaphylaxis were cutaneous tests (prick tests and intradermal tests), which minimal dilutions for specific positive skin test were previously determined by comparison with control subjects. The cutaneous tests were performed by all the centres. These tests were associated, in 29 centres, with the detection of specific IgEs against quaternary ammonium compound and inhibition test, and detection of IgEs against propofol, thiopental and latex. Moreover, leukocyte histamine release test was performed in seven centres. The mechanism of the reaction was: anaphylaxis in 692 patients (characteristic clinical symptoms and positive allergological tests), anaphylactoid reactions in 611 patients (characteristic clinical symptoms and negative allergological tests), and other causes in 345 patients (unusual clinical symptoms and negative allergological tests). An immune mechanism was found in 53% of the reactions, with characteristic clinical symptoms occurring during anaesthesia. The 692 cases of anaphylaxis were due to 734 substances (double anaphylaxis in 42 patients): muscle relaxants (61.6%), latex (16.6%), antibiotics (8.3%), hypnotics (5.1%), colloids (3.1%), opioids (2.7%) and others (2.6%) among which aprotinin (four cases) ethylene oxide (five cases) local anaesthetics (two cases). The muscle relaxants implicated in anaphylactic reactions included: vecuronium (n = 130), atracurium (n = 107), suxamethonium (n = 106), pancuronium (n = 41), rocuronium (n = 41), mivacurium (n = 18), and gallamine (n = 9). These results reflected French anaesthetic practice, except for suxamethonium (5% of the French market share of curares). In 70% of the patients who were allergic to one muscle relaxant, cross-sensitivity was found with the other relaxants. The comparison with the three previous surveys confirms that the mechanism of about half of the anaphylatoid reactions occurring during anaesthesia is of immune origin, due to specific IgE antibodies. Muscle relaxants remain the most common cause of anaphylaxis, followed by latex whose incidence seems to decrease, whereas the incidence of anaphylaxis to antibiotics increases. Incidence of reactions to suxamethonium decreased, corresponding however to one quarter of all muscle relaxant anaphylaxis, similar with vecuronium and atracurium. For this survey, more clinical information was obtained in 583 patients, allowing the following conclusions: reactions were always more severe in case of anaphylaxis than nonspecific histamine release; reactions occurred more frequently in females (F/M = 2.5); 17% of patients allergic to a muscle relaxant were never anaesthetized beforehand; a history of reactions during previous anaesthetics was a risk factor for a reaction during subsequent anaesthetics; neither drug allergy nor atopy (except for latex allergy) were a predisposing factor for reactions with anaesthetic agents. Considering that in 1996, 8 million anaesthetics were administered in France, of which 2.5 million included the use of muscle relaxants, the overall incidence for anaphylactic reactions, all agents included, was evaluated as 1 in 13,000 anaesthetics, while the incidence of anaphylaxis to muscle relaxants was 1 in 6,500 anaesthetics.

Anaphylaxis↗
PubMed1999

[The use of curare-like agents in resuscitation].

OBJECTIVE: To analyse current data on use of neuromuscular blocking agents (NBA) in the intensive therapy unit (ITU) patients and to propose practice guidelines. DATA SOURCES: We did a Medline search of French and English language articles on NBA administration in ITU patients from 1960 to 1998. Data were also selected from our own collection of articles and books. STUDY SELECTION: Original articles, clinical cases, letters to the editor and review articles were considered. DATA EXTRACTION: Data on pharmacology of NBA in the ITU patient were extracted, as well as data on administration patterns and cost. DATA SYNTHESIS: The indications for myorelaxation in ITU patients include either short term use, as in anaesthesia, or long term administration for facilitation of mechanical ventilation, control of increased intracranial pressure, status epilepticus, tetanus and oxygen demand in case of muscular hyperactivity, diagnostic and therapeutic procedures facilitation. A beneficial effect of NBA on the prognosis of the disease for which these agents have been used is not yet proven. Suxamethonium, because for its short onset time and duration of action, is the agent of choice for endotracheal intubation if myorelaxation is required. Among the benzylisoquinolines, atracurium and besilate of cisatracurium are convenient agents in ITU patients, whereas mivacurium is of no special interest. Among the aminosteroids, pancuronium and vecuronium are the most often used agents in the ITU. Rocuronium has not yet been extensively assessed. Myorelaxants carry risks for morbidity and mortality. The difficulty to assess the neurological status and the level of sedation is a recognised adverse effect. An accidental disconnection from the circuit and the resulting asphyxia is nowadays recognised without delay by the ventilator. NBAs increase the rate of bronchopulmonary infections. Cardiovascular complications include extreme bradycardia or sinus arrest following vecuronium administration, and cardiac arrest after suxamethonium injection mainly in burned or traumatised patients. Conversely to anaesthesia, NBAs do not carry a significant risk for anaphylactic or anaphylactoid complications in the ITU. Tachyphylaxis occurs mainly in burns and other pathologies modifying acetylcholine receptors. Neuromuscular complications include myopathy from steroids, postparalytic syndrome, deconditioning syndrome and intensive care polyneuropathy. Prolonged curarisation after discontinuation of NBA administration has a multifactorial origin and must be differentiated from neuromuscular complications. For prolonged neuromuscular blockade, pancuronium, vecuronium and atracurium are the agents of choice. The association with an adequate sedation is essential. Assessment of depth of neuromuscular blockade is not based on clinical symptoms but on train-of-four (TOF) twitch monitoring. A convenient basic relaxation is usually obtained with the suppression of the two last responses to TOF. CONCLUSION: The use of NBA in ITU patient should result from a rational decision making procedure, the blockade titrated with a TOF monitor and maintained as superficially and shortly as possible.

Anesthesia↗
PubMed2000

Continuous infusion of remifentanil and target-controlled infusion of propofol for patients undergoing cardiac surgery: a new approach for scheduled early extubation.

OBJECTIVE: To assess hemodynamic stability, postoperative pain management, and the control and timing of early extubation of a total intravenous anesthetic technique using propofol target-controlled infusion (TCI) and remifentanil in cardiac surgery. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Fifty patients scheduled for elective cardiac surgery. INTERVENTIONS: Premedication consisted of oral midazolam, 0.1 mg/kg. Anesthesia was induced with propofol TCI at a target concentration of 1.5 to 2 microg/mL; remifentanil, 1 microg/kg; and rocuronium. Anesthesia was maintained with propofol at the same target concentration and remifentanil titrated between 0.25 and 1 microg/kg/min. Thirty minutes before the end of surgery, a 0.1-mg/kg bolus of morphine was administered intravenously. Postoperative sedation was achieved by maintaining the propofol infusion until the patient was deemed ready for extubation. Postoperative pain relief was evaluated using a visual analog scale. The intervals between arrival in the intensive care unit, spontaneous ventilation, and extubation were recorded. MEASUREMENTS AND MAIN RESULTS: Included in this study were 36 men and 14 women (American Society of Anesthesiologist = III; New York Heart Association = II) scheduled for cardiac surgery. All patients remained hemodynamically stable throughout the perioperative period. Thirty-seven patients were successfully extubated during the first 4 postoperative hours. Spontaneous breathing was achieved at a mean interval of 15+/-5 minutes after propofol discontinuation. The mean interval to extubation was 163+/-45 minutes after arrival in the intensive care unit. Extubation was performed 48+/-12 minutes after patients were considered ready to awaken. During spontaneous ventilation, 36 patients received additional boluses of morphine (mean, 2.5+/-1 mg). Subsequently, all patients achieved a visual analog scale less than 40 mm. CONCLUSION: The combination of remifentanil and propofol TCI resulted in hemodynamic stability and good postoperative analgesia. This technique allows physicians to schedule the time of extubation in patients undergoing cardiac anesthesia.

Anesthetics, Combined↗
PubMed2003

Screening procedure for eight quaternary nitrogen muscle relaxants in blood by high-performance liquid chromatography-electrospray ionization mass spectrometry.

A screening procedure was developed for the identification and the quantification of eight quaternary nitrogen muscle relaxants, including d-tubocurarine, alcuronium, pancuronium, vecuronium, atracurium, mivacurium, rocuronium and mebezonium, in blood samples. The procedure involves ion-pair extraction with methylene chloride at pH 5.4, reversed-phase HPLC separation and electrospray ionization mass spectrometry detection. The procedure was validated in terms of linearity (0.929 5 for all the target compounds at 0.1 mg/l). The screening test was found satisfactory and applied in two fatal deaths. In the first case, toxicological investigations on biological fluids collected during the autopsy revealed the presence of vecuronium (1.2 and 0.6 mg/l in blood and urine, respectively) and its desacetylated metabolite, 3-hydroxy-vecuronium (4.4 and 0.7 mg vecuronium equivalent/l in blood and urine, respectively). In the second forensic case, blood analysis showed high levels of mebezonium (6.5 mg/l). The developed procedure was found suitable for forensic investigations.

Adult↗
PubMed2000

Non-depolarizing neuromuscular blocking activity of bisquaternary amino di- and tripeptide derivatives.

Herein we describe the synthesis of novel di- and tripeptide derivatives with two quaternary nitrogen groups attached and the biological testing of these compounds for neuromuscular blocking (NMB) activity in vitro and in vivo. The short peptide scaffold was selected because it offers potential for desired distance between the two pharmacophoric quaternary nitrogen groups, short duration of action, straightforward synthesis, and compatibility with an injectable formulation. From a small series of compounds 20c,e are identified as effective non-depolarizing NMB agents in vitro and in vivo in anesthetized cats and Rhesus monkeys with potencies similar to those of the clinical reference compounds rocuronium (4) and suxamethonium (2) (monkey ED(90) = 0.68, 0.23, 0.16, 5.04 micromol/kg, respectively). These new peptide derivatives 20c,e have similar potency and onset time but longer duration and slower recovery than the clinically used reference compounds. The structure-activity relationships described for this chemical series lead to the conclusion that the di- or tripeptide fragment can be regarded as an alternative template to the steroid or aliphatic ester of previously reported NMBs and within this tripeptide-derived series clog P correlates well with in vitro NMB activity.

Amines↗
PubMed2000

Does monitoring of post-tetanic count prevent alarms of airway pressure or visible muscle activity during intratracheal jet ventilation? A prospective study with five different neuromuscular blocking agents.

OBJECTIVE: Profound neuromuscular block (NMB) quantified by post-tetanic count (PTC) may prevent all muscle activity during anesthesia. We studied whether monitoring of PTC prevents airway pressure alarms or visible movements of the vocal cords and the abdomen during endolaryngeal procedures (ELPs). METHODS: In this prospective, double blind, study 50 healthy (ASA 1-3) patients scheduled for ELPs were randomized into five groups: atracurium, mivacurium, rocuronium, vecuronium and succinylcholine. During alfentanil-propofol anaesthesia, profound NMB was controlled by monitoring the PTC (target level PTC 0-2, 50 Hz tetanic stimulation) of the adductor pollicis muscle. The muscle relaxants were administered using bolus dosing in all groups but in the succinylcholine group. The early signs of recovery of NMB to be observed were: 1) airway pressure alarms, 2) movements of vocal cords on the laryngeal video monitor and 3) movements of the abdomen. The inference was based on 90% confidence interval tests. RESULTS: During 50 ELP:s following signs of early recovery of NMB were recognized: 2 alarms of airway pressure, 16 laryngeal movements and 11 movements of the abdomen. The proportion of airway pressure alarms was significantly lower than proportion of all detectable movements (95% confidence interval analysis). Twelve of the movements were recorded at PTC zero level. The signs of early recovery of NMB were detected in all groups. CONCLUSIONS: PTC-monitoring following 50 Hz stimulation does not ensure total inactivity of muscles during alfentanil-propofol anesthesia, regardless which relaxant has been chosen. During ELPs, simultaneous observation of the vocal cords and the abdomen is more sensitive in detecting early recovery of NMB compared to our method of airway pressure monitoring.

Abdomen↗
PubMed2003

Gender differences in drug effects: implications for anesthesiologists.

BACKGROUND: The gender aspect in pharmacokinetics and pharmacodynamics of anesthetics has attracted little attention. Knowledge of previous work is required to decide if gender-based differences in clinical practice is justified, and to determine the need for research. METHODS: Basis for this paper was obtained by Medline searches using the key words 'human' and 'gender' or 'sex,' combined with individual drug names. The reference lists of these papers were further checked for other relevant studies. RESULTS: Females have 20-30% greater sensitivity to the muscle relaxant effects of vecuronium, pancuronium and rocuronium. When rapid onset of or short duration of action is very important, gender-modified dosing may be considered. Males are more sensitive than females to propofol. It may therefore be necessary to decrease the propofol dose by 30-40% in males compared with females in order to achieve similar recovery times. Females are more sensitive than males to opioid receptor agonists, as shown for morphine as well as for a number of kappa (OP2) receptor agonists. On this basis, males will be expected to require 30-40% higher doses of opioid analgesics than females to achieve similar pain relief. On the other hand, females may experience respiratory depression and other adverse effects more easily if they are given the same doses as males. CONCLUSION: These examples illustrate that gender should be taken into account as a factor that may be predictive for the dosage of several anesthetic drugs. Moreover, there is an obvious need for more research in this area in order to further optimize drug treatment in anesthesia.

Adrenergic Agents↗