Dose-response effect of serum butyrylcholinesterase activity after clinical doses of pancuronium.

INTRODUCTION: Low-dose pancuronium is known to affect serum cholinesterase activity (BChE); however, the dose-response effect of clinical doses of pancuronium on BChE has not been investigated. METHODS: Thirteen ASA I-II patients scheduled for elective surgery requiring muscle relaxation were enrolled in this study. All patients had normal BChE before surgery. Incremental doses of pancuronium (10, 20, 50, and 100 microg/kg) were injected in accordance with surgical needs every 45 min. BChE was measured 3 min after injection by an automatic colorimetric method. RESULTS: BChE decreased significantly in all except one patient in comparison to the baseline (P < 0.05). However all values remained within normal clinical range. A dose of 100 microg/kg yielded significant decrease in comparison to 10 microg/kg but not to other dosages. Linear regression was not significant for the dose-response relationship (P = 0.05). CONCLUSION: After clinical incremental doses of pancuronium, BChE remained within clinical range.

Comparison of two induction regimens using or not using muscle relaxant: impact on postoperative upper airway discomfort.

BACKGROUND: Muscle relaxants facilitate tracheal intubation, but they are often not used for short peripheral surgical procedures. The consequences of this practice on the upper airway are still a matter of controversy. We therefore compared the incidence of post-intubation symptoms in a randomized study comparing patients intubated with or without the use of a muscle relaxant. METHODS: A total of 300 adult patients requiring tracheal intubation for scheduled peripheral surgery were randomly assigned in a double-blind study to an anaesthetic protocol that either included or did not include a muscle relaxant (rocuronium). The primary end-point was the rate of post-intubation symptoms 2 and 24 h after extubation. The secondary end-points were the intubation conditions score (Copenhagen Consensus Conference), the rate of difficult intubations (Intubation Difficulty Scale), and the incidence of adverse haemodynamic events. RESULTS: Post-intubation symptoms were more frequent in patients intubated without the use of a muscle relaxant, whether 2 h (57% vs 43% of patients; P < 0.05) or 24 h (38% vs 26% of patients; P < 0.05) after extubation. Intubation conditions were better when the muscle relaxant was used. In patients intubated without a muscle relaxant, difficult intubation was more common (12% vs 1%; P < 0.05), as were arterial hypotension or bradycardia requiring treatment (12% vs 3% of patients; P < 0.05). CONCLUSIONS: The use of a muscle relaxant for tracheal intubation diminishes the incidence of adverse postoperative upper airway symptoms, results in better tracheal intubation conditions, and reduces the rate of adverse haemodynamic events.

Low flow and economics of inhalational anaesthesia.

Even when anaesthesia does not represent a major part of the expense of a given surgical operation, reducing costs is not negligible because the large number of patients passing through a department of anaesthesia accounts for a huge annual budget. Volatile anaesthetics contribute 20% of the drug expenses in anaesthesia, coming just behind the myorelaxants; however, the cost of halogenated agents has potential for savings because a significant part of the delivered amount is wasted when a non- or partial-rebreathing system is used. The cost of inhaled agents is related to more than the amount taken up; it also depends on their market prices, their relative potencies, the amount of vapour released per millilitre of liquid, and last but not least the fresh-gas flow rate (FGF) delivered to the vaporizer--the most important factor determining the cost of anaesthesia. Poorly soluble agents like desflurane and sevoflurane facilitate the control of low-flow anaesthesia and reduce the duration of temporary high-flow phases to rapidly wash in or adjust the circuit gas concentrations. Modelling low-flow or minimal-flow anaesthesia will help anaesthetists to understand the kinetics of inhaled agents in those circumstances and to design their own clinical protocols. The monitoring facilities present on modern anaesthesia machines should convince clinicians that low- or even minimal-flow anaesthesia would not jeopardize the safety of their patients. Cost containment requires primarily a decrease in FGFs, but it may also be influenced by a rational use of the available halogenated agents. Isoflurane, the cheapest generic agent, might be advantageous for maintenance of anaesthesia of less than 3 hours. Sevoflurane is the agent of choice for inhalational induction and might also be used for maintenance. Desflurane might be preferred for long anaesthetics where rapid recovery will generate savings in the PACU.

Interaction between mivacurium and pancuronium: impact of the order of administration.

INTRODUCTION: Potentiation of mivacurium by low-dose pancuronium is mostly due to an inhibition of plasma butyryl cholinesterase (BchE) resulting in a decreased rate of hydrolysis of mivacurium. Nevertheless, an interaction at the receptor site could not be ruled out. By changing the order of the muscle relaxant injections, we may lessen the pharmacokinetic interaction and assess the impact at the acetylcholine receptor level. METHODS: Twenty patients scheduled for general anesthesia with propofol and fentanyl, and isoflurane were randomized into two groups receiving, mivacurium 100 microg kg-1 followed by pancuronium 15 microg kg-1 (group 1) or pancuronium 15 microg kg-1 followed by mivacurium 100 microg kg-1 (group 2). BchE before and after injection of each relaxant was measured. Neuromuscular block was assessed with a force transducer at the adductor pollicis measuring the elicited twitch to ulnar nerve stimulation. RESULTS: The neuromuscular block was greater when pancuronium was administered before mivacurium (100% versus 96+/-3%; P<0.05). Times to recovery of the elicited twitch response to 25% and 75% of control value were increased by 100% (P<0.05). After pancuronium, decreases in BchE of 11% and 14% in groups 1 and 2 were observed, respectively. CONCLUSION: Interaction between mivacurium and low dose pancuronium is significant only when mivacurium is injected after pancuronium.

[Postoperative nausea and vomiting: cost and therapeutic algorithm. Part II: high-risk patients and late PONV]. / Nausées-vomissements postopératoires (NVPO): avantage et coût d'un algorithme thérapeutique. Partie II: sujets à risque et NVPO tardifs.

OBJECTIVES: To evaluate in high-risk patients and in usual clinical conditions, the efficiency of treatments based on an algorithm on late (24 h) postoperative nausea and vomiting (PONV). STUDY DESIGN: Prospective and descriptive. METHODS: The nature and efficiency of prophylactic and curative PONV treatments was evaluated 24 h after surgery under general anesthesia in patients at high risk of PONV, one and 15 month after the introduction of a clinical and therapeutic algorithm. A risk score based on the type of surgery and patients characteristics determined the prophylactic treatment: high risk = droperidol 1.25 mg + ondansetron 4 mg; moderate risk = droperidol 1.25 mg. Cost of prophylactic and curative treatment was calculated according to the exact number of vials of antiemetics used. RESULTS: The use of the therapeutic algorithm leads to a reduction of PONV by a half (47.7% of 109 patients in 1999 vs. 24.5% of 102 patients in 2001) while twice more patients received a prophylactic treatment (32.1% vs. 75.5%). The number of patients needed to be treated (NNT) according to the algorithm to avoid PONV was 1.8 in this high-risk population. However, the relative risk to have PONV was only reduced by 66% with the combination of two antiemetics in 2001 and 22.5% patients still suffered from PONV despite the double prophylactic treatments. The relative risk of PONV without prophylactic treatment was spontaneously reduced by 25% between the two study periods (54% vs. 40%). After 15 months, the recommendations were followed in 43.1% of patients. A curative treatment was given in the same percentage of patients in 2001 and 1999 (63.4% vs. 68%), but followed the recommendations in fivefold more patients (47% vs. 9.1%). The cost of PONV treatment (prophylactic and curative) was increased by 3.5-fold between the two periods ( 55 for 109 patients vs. 190 for 102 patients). CONCLUSION: The use of a PONV therapeutic algorithm based on a scored risk was associated to a lower reduction of late PONV than already published in the literature while the cost was increased as expected. This suggests the efficacy of antiemetic prophylactic treatment might have been overestimated by large multicenter trials and is less in usual clinical conditions. Thus local evaluation of practice is required by performing quality insurance programs.

[Postoperative nausea and vomiting: cost and advantage induced by a quality insurance programme. Part I: post anaesthesia care unit]. / Nausées-vomissements postopératoires: avantage et coût d'un programme d'assurance qualité. Partie I: en salle de surveillance post-interventionnelle.

OBJECTIVES: To report the efficiency and direct cost induced by a quality insurance programme (QIP) aimed to reduce the incidence of post-operative nausea and vomiting (PONV) in the post-anaesthesia care unit. TYPE OF STUDY: Prospective and descriptive study. METHODS: The occurrence and treatment of PONV were prospectively recorded in the post-anaesthesia care unit in a standardised file before and following therapeutic recommendations made by volunteers component of a QIP. Prophylaxis was administered to patients according to a score of risks based on the type of surgery and patient characteristics. The real cost induced by this change of practice was evaluated according to pharmacists' accounts over 1 year. RESULTS: The QIP was associated to a 33.5% reduction of PONV relative risk and a 50% increase in prophylactic treatments. When this reduction of PONV was extrapolated to the total number of anaesthesia over 1 year, this QIP avoided PONV in 770 patients each year. The increase of cost reached 3572 as the cost by patient receiving a prophylactic treatment increased from 0.66 to 1. CONCLUSION: Despite an increase in the individual cost of PONV prophylaxis, the selection of patients by a "home" score of risk limits the indications of prophylactic treatment. Thus the increase in cost remains in acceptable ranges.

Influence of propofol concentrations on multipulse transcranial motor evoked potentials.

BACKGROUND: Motor evoked potentials can be affected by propofol anaesthesia. We studied how increasing target concentrations of propofol altered transcranial motor evoked potentials (tcMEP) during scoliosis surgery. METHODS: Fifteen patients undergoing surgery for scoliosis were anaesthetized with remifentanil and propofol without nitrous oxide or neuromuscular blocking agents (BIS<60). tcMEP were elicited by transcranial electric multipulse stimulation of the motor cortex and recording of compound action potentials from the anterior tibialis muscle. tcMEP were obtained before surgery with propofol target values set from 4 to 8 mg litre(-1), and then during surgery. Arterial propofol concentrations were measured for each tcMEP recording. RESULTS: Before surgery, increasing propofol reduced tcMEP amplitude in a dose-dependent manner, with no effect on latency. During surgery, at equivalent propofol concentrations, tcMEP were not statistically different from those obtained before surgery. In all except one patient, tcMEP signals were present during the entire procedure. In this patient the loss of tcMEP was unfortunately related to an anterior spinal cord lesion, which was confirmed by a wake-up test. CONCLUSION: We found that, although propofol had a dose-dependent effect on tcMEP amplitude, anaesthesia could be maintained with remifentanil and propofol to allow recording and interpretation of tcMEP signals.

[General anesthesia]. / Anesthésies générales.

General anaesthesia is a reversible loss of consciousness induced and maintained with a hypnotic drug given either by venous injection and infusion, or by inhalation. A potent opioid is usually associated to inhibit the transmission of pain and thus to lessen sympathetic and endocrine reactions to nociceptive stimuli. Myorelaxation is used to facilitate tracheal intubation and surgery. Whatever the anaesthetic protocol use, the patient and anaesthesia machine require close monitoring. In addition to vital signs, the depth of anaesthesia may be monitored using automated electroencephalographic analysis and myorelaxation should always be monitored using a nerve stimulator, but pain or analgesia evaluation is only based on clinical signs of sympathetic stimulation. Because anaesthesia-related death and morbidity have decreased considerably, future improvements in outcome should concern perioperative comfort, i.e. prevention of cognitive disturbances, nausea, vomiting and pain.

Induction with propofol target-concentration infusion vs. 8% sevoflurane inhalation and alfentanil in hypertensive patients.

Haemodynamic parameters during an inhalation induction with 8% sevoflurane were compared with those obtained with a target-controlled infusion of propofol in 50 hypertensive patients in a prospective randomised study. Heart rate and arterial pressure were recorded continuously. End-tidal sevoflurane and nitrous oxide concentration, SpO2 and bispectral index (BIS) were also collected from the beginning of anaesthesia until 8 min after tracheal intubation. Patients either received 4 mg.l-1 target-concentration propofol or performed a vital capacity inhalation of 8% sevoflurane in a high flow of oxygen (8 l.min-1) supplemented with 50% nitrous oxide at loss of consciousness. As soon as BIS was < 60, 20 microg.kg-1 alfentanil and 0.6 mg.kg-1 rocuronium were injected and orotracheal intubation was then performed 1 min later. Thereafter, the end-tidal concentration of sevoflurane was reduced to 1.3 minimum alveolar concentration (MAC). Hypotension was defined as a 30% decrease in arterial pressure and was treated with repeated 3-mg boluses of ephedrine. When 12 mg ephedrine was unable to correct hypotension, the concentration of propofol was reduced by 1 mg.l-1 and that of sevoflurane by 0.5%. Hypotension occurred in 22 patients in the sevoflurane group and 21 in the propofol group, and hypertension occurred in two and three patients in each group, respectively. The maximal reduction in mean (SD) arterial pressure was similar in the sevoflurane (45 (4) mmHg) and propofol (41.3 (2.6) mmHg) groups, as were the ephedrine requirements (9.6 (1.1) vs. 9.1 (1.1) mg, sevoflurane vs. propofol, p > 0.05), the duration of hypotension (276 (37) vs. 292 (38) s, sevoflurane vs. propofol, p > 0.05), and the number of hypotensive episodes or anaesthetic changes and depth of anaesthesia. Nevertheless, heart rate was lower during the 8 min following tracheal intubation in the sevoflurane group. In both groups, the duration of hypotension was easily controlled either by ephedrine or by adjusting the anaesthetic concentrations. Overall, haemodynamic tolerance appears to be similar in the two techniques. Because hypotension occurred after alfentanil in most patients, this study questioned which is the best opioid dose, if any, to associate with propofol or sevoflurane for the induction in hypertensive patients.

New halogenated agents: should I change my practice?

Sevoflurane and Desflurane are relatively new halogenated agents which make induction and control of depth of anaesthesia easier, recovery rapid and of good quality and they have less side-effects and toxicity. In children sevoflurane could replace halothane because it provides smooth and rapid induction with less cardiovascular depression and arrhythmias. Desflurane is not used because of its pungent odour. In adults sevoflurane could be preferred to desflurane because it allows rapid induction and laryngeal mask insertion or tracheal intubation without myorelaxants, a similar time of recovery, no clinical evidence for renal and hepatic toxicity, no more costs for anaesthesia for a lower MAC.

Plasma interleukin-4, interleukin-10, and interleukin-13 concentrations and complications after coronary artery bypass graft surgery.

OBJECTIVES: To determine whether plasma interleukin (IL)-4, IL-10, and IL-13 concentrations are associated with complications after coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). STUDY DESIGN: Prospective descriptive study. SETTING: University teaching hospital. PARTICIPANTS: Thirty-two patients during and 24 hours after CABG surgery. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements and blood samples were obtained from 32 patients during and after surgery. Coagulation, pulmonary, and cardiovascular functions were specifically assessed during the first 24 hours postoperatively. Plasma IL-4 and IL-13 levels remained unchanged during CABG surgery. In contrast, plasma IL-10 concentrations increased by 117-fold in the immediate postoperative period and returned to pre-CPB values by 24 hours postoperatively. Plasma IL-10 levels were not different in patients with or without cardiovascular impairment, coagulation disorders, and lung injury. Plasma IL-10 levels did not correlate with the leukocyte count, the amount of catecholamines infused, or the duration of CPB. CONCLUSION: The present results suggest that the development of post-CABG surgery complications might be linked to an insufficient production of anti-inflammatory cytokines, such as IL-4, IL-10, or IL-13, which are unable to counteract the overproduction of inflammatory cytokines.

Thrombelastogram reveals hypercoagulability after administration of gelatin solution.

We have compared the effects of gelatin, low molecular weight hydroxyethyl starch (HES) or albumin on tests of haemostasis and on the thrombelastogram in 42 ASA I patients undergoing total hip or knee replacement. Patients were allocated randomly to receive one of the three blood substitutes to obtain moderate intraoperative haemodilution. Blood loss and packed red cell infusion was the same in each group. A greater amount of gelatin was given (1.5 times the measured blood loss) because of its shorter half-life. There was a statistically significant but clinically negligible decrease in platelets count, prothrombin time and fibrinogen, and an increase in bleeding time in all groups. Platelets were slightly but significantly lower after HES. Haemodilution was comparable between groups. TEG showed a state of hypercoagulability in the gelatin group with a significant decrease in r, r + k and an increase in alpha angle.

Are lipid mediators implicated in the production of pro- and anti-inflammatory cytokines during cardiopulmonary bypass graft with extracorporeal circulation?

In this study the authors assessed the sequential release of lipid mediators (TXB2, PGE2, 6-keto-PGF1alpha, LTB4, LTC4, PAF), pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha) and anti-inflammatory cytokines (IL-4, IL-10) in 17 patients undergoing coronary artery bypass graft (CABG) with extracorporeal circulation (ECC). Time course of appearance of inflammatory mediators revealed the early and transient increase in lipid mediator plasma concentrations (6-keto-PGF1alpha, LTB4, LTC4, PAF) whereas cytokines (IL-6, IL-8, IL-10) were involved only in late pre- and post-operative periods. No variation of TXB2, PGE2, IL-4 and TNF-alpha levels were found. No correlation was documented between the levels of lipid mediators and pro- or anti-inflammatory cytokines suggesting that lipidic compounds are not implicated in the genesis of cytokines which appear much later involved. Despite the common use of high doses of aprotinin (a non-specific enzyme inhibitor) in hope to abrogate the inflammatory response to cardiopulmonary bypass procedure, this study reports the persistent release of several inflammatory compounds that might be involved in the post-CABG multiple organ failure syndromes.

[Accessory anesthetic breathing systems: verification before use]. / Circuits anesthésiques accessoires: vérification avant utilisation.

Accessory or ancillary anaesthesia breathing systems can be defined as all those connected to the fresh gas outlet of the anaesthetic apparatus and used instead of the circle system associated with the ventilator, which is the main circuit. They include: the Mapleson systems, the systems with a nonrebreathing valve and the disposable systems with a carbon dioxide absorber. They can be a cause of major accidents when not checked before and monitored during use. This technical note describes techniques of preanaesthetic checking and monitoring during anaesthesia.

[Anesthetic equipment: fresh gas delivery systems. II. Electronic systems]. / Appareil d'anesthésie: systèmes d'alimentation en gaz frais. II. Systèmes électroniques.

OBJECTIVES: To analyse the design, functioning, benefits and drawbacks of electronic fresh gas delivery units (FGDUs) included in anaesthetic machines marketed in France in 1999. DATA SOURCES: Articles were obtained from a Medline review (1980-1999; search terms: anaesthetic machine, flowmeter, vaporizer), textbooks and personal files; specific data were also provided by manufacturers. STUDY SELECTION AND DATA EXTRACTION: The articles were analysed in considering the differences between mechanical and electronic FGDUs. DATA SYNTHESIS: Four anaesthetic machines out of 11 are equipped with electronic FGDUs. In comparison to mechanical units, they include the following benefits: wide range of accurate gas flow, especially in the low flow range, with analog and digital display; intermittent delivery of each gas, which is essential for automated gas delivery and quantitative anaesthesia or target controlled (FET vapor) inhalational anaesthesia; facilitated oxygen ratio control; possibility to print the gas and vapor flows on the automated anaesthetic record; interruption of gas flow when the main switch of the machine is set to off; and absence of risk for retropollution. Three FGDUs out of four are adapted for gas delivery to an accessory (ancillary) anaesthetic circuit. However, only one of them delivers a gas flow up to 30 L.min-1. The specificity of the ADU AS/3 (Datex-Ohmeda) is the bypass vaporizer included in the FGDU with an exchangeable vaporizing chamber (cassette). The specificity of the Julian (Dräger) is the delivery of fresh gas limited to the expiratory phase during mechanical ventilation. The specificity of the the FGDU from Kion (Siemens) is the possibility to act as an open circuit ventilator, similar to a Servoventilator. The specificity of the PhysioFlex is an FGDU included in the circle circuit, each gas and liquid anaesthetic being directly injected into the circuit. Data from the French medical device surveillance commission indicate that the main failures occur in the power supply device and the microprocessor.

[Anesthesia equipment: fresh gas delivery systems. I. Mecanical systems with rotameters and calibrated vaporizers]. / Appareil d'anesthésie: systèmes d'alimentation en gaz frais. I. Systèmes mécaniques avec rotamètres et vaporisateurs calibrés.

OBJECTIVES: To analyse the design, performance, failures, the checking before use of mechanical fresh gas delivery units (FGDUs) equipped with bobbin or ball-flowmeters delivering a continuous gas flow and calibrated vaporizers, marketed in France in 1999. DATA SOURCES: Articles were obtained from a Medline review (1960-1999; search terms: anaesthetic machine, flowmeter, vaporizer), textbooks and personal files; specific data were provided by manufacturers. STUDY SELECTION AND DATA EXTRACTION: The articles were considered for performance data, benefits and drawbacks, and characteristics, as well as the risks carried by mechanical FGDUs. DATA SYNTHESIS: Seven anaesthetic machines out of 11 are equipped with mechanical FGDUs, including rotameters delivering a gas mixture up to 30 L.min-1, calibrated vaporizers and an O2-flush valve delivering at least 500 mL O2 per second (30 L.min-1). These units allow closed circuit anaesthesia. They carry a risk for barotrauma as three out of them can deliver at the gas outlet of the FGDUs a gas mixture at a pressure reaching 3.5 bars and four others at a pressure of 150-200 mmHg. They also carry a risk for hypoxia, either from a preferential leak of oxygen at the corresponding rotameter or the O2-flush valve, or from a leak of fresh gas mixture either in a vaporizer or the selectatec manifold. The vaporizers carry a risk for vapor delivery at a concentration differing notably from the value set on the concentration dial. Therefore their accuracy must be checked periodically and the FGDUs checked for a leak after the addition to or the removal of a vaporizer from the selectatec manifold. The optimal technique for leak detection is the negative pressure test.