P. Feiss

The role of hyaluronidase on lidocaine and bupivacaine pharmacokinetics after peribulbar blockade

Orbital regional anesthesia is the only circumstance where hyaluronidase is routinely added to local anesthetics to accelerate the onset of the block.The aim of this study was to compare the pharmacokinetics of lidocaine and bupivacaine with or without hyaluronidase for peribulbar blockade. Twenty-one patients scheduled for cataract surgery with lens implantation were included in this prospective randomized study. Peribulbar blocks were achieved with plain bupivacaine 0.5% (5.5 mL), lidocaine 2% (5.5 mL), and hyaluronidase (100 IU = 2 mL) (n = 10) or sterile water (2 mL) (n = 11). Plasma bupivacaine and lidocaine concentrations were measured by high-performance liquid chromatography at regular intervals from the end of the local anesthetic injection until the 360th minute. Maximum plasma concentration (Cmax) and time to reach Cmax (Tmax) were obtained for all the patients except one who needed a supplementary injection and was excluded from the study. The time to onset and duration of the analgesia and akinesia were monitored at the times of sampling. Motor blockade was incomplete in two patients in each group without affecting surgery. The Tmax and absorption half-life (t1/2a) of lidocaine and bupivacaine were not different within each group (P > 0.05). The Tmax of lidocaine was shorter in the presence of hyaluronidase (17.1 +/- 2.6 min vs 32.7 +/- 6.0 min) as well as the Tmax of bupivacaine (16.8 +/- 3.9 min vs 26.5 +/- 4.4 min). The Cmax of lidocaine and bupivacaine were not modified by the addition of hyaluronidase. The clearance, terminal half-life, and volume of distribution were not different between groups. The absorption of lidocaine and bupivacaine from the peribulbar space are hastened by the addition of hyaluronidase. The Tmax of lidocaine is not different from that of bupivacaine within each group suggesting that the absorption of local anesthetics is minimally influenced by the liposolubility of the drugs. Moreover, hyaluronidase influences the absorption kinetics of both lidocaine and bupivacaine in the same manner. (Anesth Analg 1996;82:1060-4)

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.

Cytokine and lipid Mediator Blood Concentrations After Coronary Artery Surgery

This study investigates whether increased levels of cytokines and lipid mediators may be associated with complications after coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC).Hemodynamic measurements and blood samples were obtained in 32 patients before and after the end of ECC and at the 6th and the 24th postoperative hours. Coagulation and pulmonary and cardiovascular functions were specifically assessed post-operatively at the same time. Patients with cardiovascular dysfunction had higher interleukin 8 (IL-8) levels. Higher platelet-activating factor (PAF) and decreased PAF acetylhydrolase activity (AHA, the enzyme that inactivates PAF) levels were found in patients with moderate cardiovascular dysfunction. Interleukin 6 (IL-6), IL-8, and AHA levels correlated with most hemodynamic parameters and creatine phosphokinase myocardial band levels obtained after surgery. Patients with severe lung injury had lower PAF, 6-keto prostaglandin (Pg)F1 alpha, and PgE2 levels and higher thromboxane (Tx) B2 concentrations compared with patients without lung injury. Increased IL6 levels were only associated with moderate lung injury. Impaired hemostasis was associated with higher IL6 levels. AHA, IL-6, and IL-8 seem to be associated with cardiovascular dysfunction. The IL-6 blood levels and the ratio of TxB2/6 keto-PgF1 alpha blood levels are increased during post-CABG lung injury. These results identify an association between specific post-CABG complications and the systemic inflammatory response. The clinical significance of this association remains to be evaluated. Implications: Patients with pulmonary, cardiovascular, or hemostasis dysfunction after cardiopulmonary bypass demonstrate aberrancies in a variety of cytokines and lipid mediators in arterial blood or plasma. The relationship between these findings and inflammatory response-induced complications remains to be determined. (Anesth Analg 1997;85:1240-6)

Low alfentanil target-concentrations improve hemodynamic and intubating conditions during induction with sevoflurane

PurposeTo investigate the effects of different alfentanil target-concentrations on hemodynamics, respiration and conditions of tracheal intubation during an inhalation induction with 8% sevoflurane.MethodsIn this prospective randomized open-label study, 40 ASA 1 adult patients received alfentanil at the following target-concentrations: zero (Group 0), 25 (Group 25), 50 (Group 50) and 75 ng·mL−1 (Group 75), starting five minutes before induction of anesthesia with 8% sevoflurane in 50% nitrous oxide. The ease of intubation was determined on fixed criteria and scored; arterial pressure, heart rate and bispectral index (BIS) were recorded at one-minute intervals.ResultsTimes to allow tracheal intubation were shortened only in Group 75 (94 ± 8 sec) as compared to Group 0 (140 ± 11 sec,P < 0.05). BIS values, tracheal intubation scores and number of attempts were not different between groups. However, more patients suffered from apnea in Group 75. Heart rate and mean arterial pressure remained stable in Group 75 whereas they increased significantly in the three other groups. No patient suffered hypotension.ConclusionAdding alfentanil at a 75 ng·mL−1 target-concentration during an inhalation induction with 8% sevoflurane in 50% nitrous oxide allows intubation slightly earlier and provides stable hemodynamic conditions but the incidence of apnea during induction is higher. Lower concentrations are of little clinical interest.RésuméObjectifRechercher les effets de différentes concentrations cibles d’alfentanil sur l’hémodynamique, la respiration et les conditions d’intubation endotrachéale pendant l’induction par inhalation de sévoflurane à 8%.MéthodeL’étude prospective, randomisée et ouverte comportait 40 patients adultes d’état physique ASA 1 recevant de l’alfentanil selon les concentrations cibles suivantes: zéro (Groupe 0), 25 (Groupe 25), 50 (Groupe 50) et 75 ng·mL−1 (Groupe 75), cinq minutes avant l’induction de l’anesthésie avec du sévoflurane à 8% dans 50 % de protoxyde d’azote. La facilité d’intubation a été évaluée d’après des critères fixes, et cotée; la tension artérielle, la fréquence cardiaque et l’index bispectral (BIS) ont été notés à intervalles d’une minute.RésultatsL’intervalle précédant l’intubation endotrachéale a été plus court dans le Groupe 75 (94 ± 8 sec) comparé au Groupe 0 (140 ± 11 sec, P < 0,05). Les valeurs de BIS, les scores à l’intubation et le nombre d’essais nécessaires n’ont pas présenté de différence intergroupe. Plus de patients ont souffert d’apnée dans le Groupe 75. La fréquence cardiaque et la tension artérielle moyenne sont demeurées stables dans le Groupe 75, mais ont augmenté significativement dans les trois autres groupes. Aucun patient n’a présenté d’hypotension.ConclusionL’ajout d’alfentanil selon une concentration cible de 75 ng·mL−1 pendant l’induction de l’anesthésie, par inhalation de sévoflurane à 8 % dans 50 % de protoxyde d’azote, permet d’intuber un peu plus tôt et fournit des conditions hémodynamiques stables, mais augmente l’incidence d’apnée pendant l’induction. Les concentrations plus faibles sont sans intérêt clinique.

Le PhysioFle™: ventilateur de circuit fermé autorégulé d'anesthésie par inhalation à objectif de concentration

Physi Flex is the first commercially available apparatus capable for quantitative, or self-regulating target controlled inhalational anaesthesia, with a totally closed circuit, in adults and children. The fresh gas supply to the circuit is intermittent, automatically regulated by continuous monitoring of the volume and composition of the gas mixture in the breathing circuit. The circle system includes, instead of the two conventional one way valves, a blower creating a continuous unidirectional flow at 70 L.min-1. In addition to the CO2-absorber it contains an absorber with carbon, absorbing the anaesthetic vapour when switched into the circuit. The ventilator consists of four ventilating chambers, each one with a membrane separating the patient and the motor compartments. The displacement of the membranes generates and measures the tidal volume. Automatic ventilation is achieved by electric valves and motor gas, and manual ventilation using a bag. Spontaneous ventilation is also possible. The machine is operated via a computer with selects the number of ventilating chambers (one, two or four), and the tidal volume between 50 and 2,000 mL, depending on age, gender and weight of the patient. The computer maintains the gas volume and the gas and vapour concentrations at their preset values. The O2-flow and consumption, the N2O flow and uptake, FICO2 and FETCO2, FI and FET of the volatile anaesthetic, all other important data are displayed in a numerical and graphical form on a color screen and registered for a delayed analysis. The end tidal concentration of the volatile anaesthetic drives a stepmotor with a syringe containing the selected volatile anaesthetic agent with is directly injected into the breathing circuit where it is vaporized. Therefore the concentration of the anaesthetic vapour can be instantaneously increased with this injector at induction and lowered at end of anaesthesia with the carbon absorber, and the fresh gas consumption is significantly decreased.

Pour ou contre les circuits anesthésiques accessoires. II. Arguments contre leur utilisation

When compared to the circle system alternative breathing systems (ABS) are of no benefit. When the only indication of an ABS is emergency oxygen administration it should be connected to the O2 pipeline upstream from the flowmeter bank and the vaporiser. The use of an ABS for anaesthesia maintenance is no longer justified because of the difficulties in monitoring pressure, flow and concentrations of the gas mixture, the cost of gas and vapour administered at a high flow and the resulting pollution. The use of an ABS for very short anaesthetics is only acceptable if the administered gas mixture is monitored.When compared to the circle system alternative breathing systems (ABS) are of no benefit. When the only indication of an ABS is emergency oxygen administration it should be connected to the O2 pipeline upstream from the flowmeter bank and the vaporiser. The use of an ABS for anaesthesia maintenance is no longer justified because of the difficulties in monitoring pressure, flow and concentrations of the gas mixture, the cost of gas and vapour administered at a high flow and the resulting pollution. The use of an ABS for very short anaesthetics is only acceptable if the administered gas mixture is monitored.

Prévention des nausées et vomissements postopératoires par l'ondansétron

This study was carried out to assess the efficacy of oral ondansetron, a new 5HT3 receptor antagonist, in patients undergoing thyroid surgery. It included 60 patients, randomly assigned to two groups, and receiving orally, 1 h before induction of anaesthesia, either 8 mg of ondansetron (n = 29) or a placebo (n = 30). One patient was excluded. The same anaesthetic protocol, consisting of 3 to 5 μg · kg−1 of fentanyl, 4 to 6 mg · kg−1 of thiopentone, and 0,5 mg · kg−1 of atracurium, was used in all. Anaesthesia was maintained with 50 % nitrous oxide in oxygen with 0.8 to 1 % endtidal concentration of isoflurane and additional boluses of 0.1 mg of fentanyl as required. The incidence and intensity of nausea, graded mild, moderate or severe, and the incidence of vomiting were recorded postoperatively. During the first twelve hours after surgery, 40 % of patients in the placebo group had nausea (16.7 % mild, 20 % moderate and 6.7 % severe), and 50 % vomited. In the ondansetron group, nausea and vomiting occurred in 13.8 % and 20.4 % of patients respectively. The 4 patients in the latter group complained of major nausea. The differences between the groups were statistically significant : p = 0.025 for nausea and p = 0.042 for vomiting. It is concluded that oral ondansetron, 8 mg taken orally 1 h before surgery, significantly reduces the incidence of nausea and vomiting during the first twelve postoperative hours. As it is easy to use and has no side-effects, it might be of interest in day-case surgery patients, despite its high cost.

Potentiation of Mivacurium blockade by low dose of pancuronium: A pharmacokinetic study

BACKGROUND Mivacurium is potentiated by pancuronium to a much greater extent than other relaxants. In a previous investigation we suggested that this potentiation could be due to the ability of pancuronium to inhibit plasma cholinesterase activity, but we did not measure plasma concentrations of mivacurium. In the current study we performed a pharmacokinetic analysis by measuring the plasma concentration of mivacurium when preceded by administration of a low dose of pancuronium. METHODS After induction of general anesthesia with propofol and fentanyl and orotracheal intubation, 10 patients (pancuronium-mivacurium group) received 15 microg/kg pancuronium followed 3 min later by 0.1 mg/kg mivacurium, whereas 10 other patients (mivacurium group) received saline followed by 0.13 mg/kg mivacurium 3 min later. Plasma cholinesterase activity was measured before and 3 and 30 min after pancuronium dosing in the pancuronium-mivacurium group and was measured before and after administration of saline in the mivacurium group. Arterial plasma concentrations of mivacurium and its metabolites were measured at 0.5, 1, 1.5, 2, 4, 10, 20, and 30 min after injection. Neuromuscular blockade was assessed by mechanomyography. RESULTS Plasma cholinesterase activity decreased by 26% in the pancuronium-mivacurium group 3 min after injection of pancuronium (P < 0.01) and returned to baseline values 30 min later; however, no significant variation was observed in the mivacurium group. The clearances of the two most active isomers (Cis-Trans and Trans-Trans) were lower in the pancuronium-mivacurium group (17.6 +/- 5.1, 14.7 +/- 5.3 ml. min-1. kg-1, respectively) than in the mivacurium group (32.4 +/- 20.2, 24.8 +/- 13.5 ml. min-1. kg-1; P < 0.05). CONCLUSIONS A subparalyzing dose of pancuronium decreased plasma cholinesterase activity and the clearance of the two most active isomers of mivacurium. Pancuronium potentiates mivacurium more than other neuromuscular blocking agents because, in addition to its occupancy of postsynaptic acetylcholine receptors, it slows down the hydrolysis of mivacurium.

The cardiovascular effects of mivacurium in hypertensive patients

UNLABELLED Hypotension is common after mivacurium injection in healthy patients. This hemodynamic event had not been investigated in hypertensive patients characterized by more intense hemodynamic instability. In this open-label, multicenter, randomized, and controlled study, we sought to determine whether mean arterial blood pressure (MAP) and heart rate variations were larger in hypertensive versus normotensive patients after a bolus dose of mivacurium injected over 10 or 30 s. After the induction of anesthesia with fentanyl and etomidate, normotensive (n = 149) and hypertensive (n = 57) patients received a single dose of mivacurium 0.2 mg/kg injected over 10 or 30 s by random allocation. Heart rate and MAP were recorded electronically. The incidence of hypotension (defined as a 20% MAP decrease from the control value before mivacurium injection) was 21% and 36% (10-s injection) or 11% and 10% (30-s injection) in the Normotensive and Hypertensive groups, respectively. In Hypertensive patients, the maximum decrease in MAP was significantly greater when mivacurium was injected over 10 s compared with 30 s: 20% vs 11%, respectively (P = 0.002). This difference was not observed in Normotensive patients. Hypotension after rapid (e.g., 10 s) mivacurium injection was more frequent and more pronounced in Hypertensive than in Normotensive patients. IMPLICATIONS When mivacurium (0.2 mg/kg) is injected rapidly (e.g., 10 s) the incidence and the intensity of hypotension are greater in hypertensive patients than in healthy patients.

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.