Colette Franssen

Increase in antioxidant capacity of plasma during propofol anesthesia

We have examined the effect of total intravenous anesthesia (TIVA) using a continuous propofol infusion on the antioxidant capacity of plasma in 18 neurosurgical patients who required cerebrospinal fluid shunting. Patients were premedicated with hydroxyzine, alprazolam, and atropine. Anesthesia was induced intravenously with propofol 1.5 mg kg-1 and sufentanil 0.15-0.3 microgram kg-1. Tracheal intubation was facilitated with atracurium 0.5 mg kg-1. Anesthesia was maintained with a continuous propofol infusion at an increasing rate from 6 to 12 mg kg-1 h-1 under controlled ventilation (FiO2 = 0.4 in air). In all patients, arterial blood samples were drawn before induction of anesthesia and during surgery for measurement of blood propofol concentration and plasma antioxidant capacity, which was assessed as the ability to inhibit lipid peroxidation. Lipid peroxidation was induced in vitro by exposing a linoleic acid microemulsion to hemoglobin-generated oxoferryl radicals, and assessed by ultraweak chemiluminescence in the absence (control) and the presence of the plasma samples. The antioxidant capacity of plasma, measured by the inhibition of light emission and expressed as a percentage of control, increased significantly from 39.8 +/- 2% (mean +/- SEM) to 44.7 +/- 2.4% during anesthesia (Wilcoxon test, p < 0.001). No correlation was observed between this increased resistance to lipid peroxidation and blood propofol concentrations (Spearman test, r = 0.07, NS). We conclude that the capacity of plasma to inhibit lipid peroxidation increases in patients during TIVA maintained with a continuous propofol infusion.

Evidence of in vivo Free Radical Generation by Spin Trapping with α-Phenyl N-Tert-Butyl Nitrone During Ischemia/Reperfusion in Rabbit Kidneys

By using alpha-phenyl N-tert-butyl nitrone (PBN) as spin trap molecule and the electron paramagnetic resonance (EPR) technique, we obtained the first direct evidence of in vivo intervention of free radicals during an ischemia (50 minutes) reperfusion phenomenon in kidney of an intact rabbit. An EPR signal (triplet of doublets) characterized by coupling constants aN = 14.75-15 G and aH beta = 2.5-3 G was detected in blood samples. The signal was consistent with a nitroxyl-radical adduct resulting from the spin trapping by PBN of either oxygen-or carbon-centered radicals. Control experiments indicated that the EPR signal was not due to a toxic effect of the spin trap molecule.

Comparison between alprazolam and hydroxyzine for oral premedication

The safety and efficacy of alprazolam and hydroxyzine administered orally as surgical premedicants were compared in a double-blind controlled study. Sixty-five patients were given either alprazolam 1 mg or hydroxyzine 75 mg, one to two hours before surgery. Anxiety was assessed by both the patient and the anaesthetist, the patient using a visual analogue scale, the anaesthetist employing both analogue and ordinal ratings. Sedation was assessed by the anaesthetist only, using the same two methods. Amnesia was appraised with a simple memory test. Safety was assessed by recording adverse effects and measuring haemodynamic variables. Premedication with alprazolam produced a modest reduction in anxiety (28%) (P < 0.01) while hydroxyzine had no detectable effect. The comparison of the sedation level and of the memory test revealed no difference between the two premedicants. Minor side effects were only observed in the hydroxyzine group. Changes in blood pressure were more pronounced in the hydroxyzine group. This study shows that alprazolam and hydroxyzine are safe and efficient oral premedicants. However, alprazolam is preferable to hydroxyzine in terms of anxiolytic and adverse effects.RésuméAu cours d’une étude à double insu, on compare la sécurité et l’efficacité de l’alprazolam et de l’hydroxyzine administrés par voie orale en prémédication. Soixante-six patients reçoivent alprazolam 1 mg ou hydroxyzine 75 mg de une à deux heures avant la chirurgie. Le patient et l’anesthésiste évaluent individuellement le degré d’anxiété: le patient utilise une échelle visuelle analogique alors que l’anesthésiste utilise une classification ordinale en plus de l’échelle analogique. Grâce à ces deux méthodes, le sédation fait l’objet d’un évaluation par l’anesthésiste seul. L’amnésie est estimée par une test de mémoire simple. On évalue la sécurité des médicaments par l’enregistrement des effets défavorables et la mesure des variables hémodynamiques. La prémédication à l’alprazolam produit une baisse modeste de l’anxiété (28%) (P < 0,01) alors que l’hydroxyzine ne produit pas d’effets décelables. La comparaison entre les deux prémédications pour le degré de sédation et le test de mémoire ne révèle pas de différence. Des effets secondaires mineurs ne sont observés que dans le groupe hydroxyzine. Les changements tensionnels sont plus prononcés dans ce dernier groupe. Cette étude démontre que l’alprazolam et l’hydroxyzine sont en prémédication des médicaments sûrs et efficaces. Cependant l’alprazolam est supérieur à l’hydroxyzine sous l’aspect de l’anxiolyse et des effets secondaires.

The effect of technical conditions and storage medium composition on the phosphomonoesters to inorganic phosphate ratio determined by 31P nuclear magnetic resonance spectroscopy in rabbit kidney

Using 31P nuclear magnetic resonance spectroscopy, we compared the state of the high-energy phosphates in rabbit kidneys stored at 4±C for 24 hr with 3 different solutions: Ringer (Rg), University of Wisconsin (UW), and EuroCollins (EC) solutions. We found the highest phosphomonoester/inorganic phosphate (MP:Pi) ratio in the group of kidneys stored in the Rg solution (Rg, 0.93 ± 0.04; UW, 0.36 ± 0.02; EC, 0.28 ± 0.02). This medium has been demonstrated in previous physiological studies to give poor results in terms of organ preservation compared to the solutions that mimic the “intracellular” fluid, such as the EC and UW solutions. Because the commonly used cold storage solutions contain phosphates, which superimpose on the intracellular Pi and, thus, can distort the results, we attempted to eliminate the contaminating solution around the kidney and in the vasculature by flushing the kidney with a phosphate-free solution (Rg). The MP:Pi ratio increased in the UW and EC groups (UW, 0.82 ± 0.04; EC, 0.64 ± 0.04) in identical proportion in the 2 groups. It remained highest in the Rg group (1.02 ± 0.03). Comparisons of data before and after flush showed that external phosphate contamination was not predominant. There was no equilibrium in phosphate distribution between intra-and extracellular spaces at 24 hr of storage. We conclude that the validity of the MP:Pi ratio, as a viability index of renal transplant, might have to be restricted to comparisons of kidneys preserved in the same storage conditions. Therefore, it would be necessary to establish normal and pathological values of this ratio for each cold storage solution.

Plasma myeloperoxidase and vitamin E levels in head injury: preliminary results related to outcome.

This preliminary study was designed to assess a possible role of neutrophil activation and to determine the prognostic value of plasma myeloperoxidase (MPO) and vitamin E (Vit. E) levels in severe head injury. Plasma MPO and Vit. E levels were measured in nine severely head-injured patients (Glasgow Coma Score </=8) (ages 12-80 years) 6, 12. 18, 24, and 30 h after trauma. Patients were classified into two groups according to outcome after discharge from the ICU: group D (death; n = 5) and group S (survival; n = 4). Plasma MPO levels were increased immediately after trauma and then decreased. The MPO peak observed after 6 h was significantly higher (p < 0.05) in group D (mean +/- SEM: 1,237 +/- 122 ng/ml) than in group S (mean +/- SEM: 543 +/- 148 ng/ml). Plasma Vit. E levels were lower than normal values and decreased over time. They were always significantly lower (p < 0.05) in group D than in group S, except for the first sample. These differences cannot be explained entirely by total plasma lipid (TL) values since no statistical difference in TL concentrations was found between the two groups during the course of study. The ratio of Vit. E to TL. considered as the best index of Vit. E status, was lower in group D than in group S. and the difference reached statistical significance (p < 0.05) 12 h after trauma. In conclusion, in spite of the limited number of patients included in this study, it appears that severe head injury is associated with an increase in MPO and a decrease in Vit. E levels. These biochemical changes are of greater magnitude in group D than in group S; they suggest neutrophil activation and lipoperoxidation processes. Finally, plasma MPO and Vit. E seem to be new discriminant factors of outcome in head-injured patients.

Protection cérébrale: données expérimentales

Le concept de protection cerebrale fait reference a toute mesure pharmacologique ou non pharmacologique, qui, instauree avant ou concomitamment a une agression hypoxique ou ischemique, entraine une amelioration significative de la fonction neurologique. La protection cerebrale reste encore aujourd’hui un formidable defit. En effet, en ce debut du troisieme millenaire, les medecins confrontes aux patients a risque d’hypoxie ou d’ischemie s’interrogent toujours pour savoir dans quelle mesure cet objectif doit etre considere comme un reve impossible ou une realite naissante. Deux raisons essentielles sont a l’origine de cette etonnante perplexite. La premiere reside dans la connaissance de cette pathologie, qui est un prealable indispensable a l’instauration d’une therapeutique efficace, preventive et curative. Or, l’ischemie cerebrale declenche une cascade extremement complexe de reactions physiopathologiques et entraine une multitude de reactions biochimiques, inflammatoires et geniques dont la finalite reste imparfaitement comprise. La seconde raison est liee au fait qu’une therapeutique benefique au plan experimental ne peut etre transposee de maniere systematique a une situation clinique. En d’autres termes, en depit des avancees indeniables de la recherche fondamentale et de l’experimentation animale, les mesures de protection cerebrale qui ont fait leur preuve en clinique humaine restent encore a ce jour tres limitees.