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Biomedical subjects

P Hans

Publications and source records attributed to P Hans.

At least 55 records · Page 3Linked to original sources

Neuroprotection with anaesthetic agents.

The term 'neuroprotection' is used to refer to any prophylactic measure that is initiated during the peri-ischaemic period in order to improve neuronal survival. Cell death after ischaemia has an immediate, necrotic and a delayed, apoptotic origin. The major biochemical mechanisms that are involved in this process include transmembrane ionic fluxes and intracellular calcium increase, excitotoxicity, free radical formation, peroxynitrite production, release of inflammatory mediators, mitochondrial dysfunction, cytochrome c release, and activation of caspases and transcription factors. Strategies of neuroprotection essentially impact on those biochemical pathways. The label 'neuroprotectant' requires that the therapy has basic properties that are consistent with potential mechanisms of neuroprotection, and that conclusive results are available from animal studies that can be converted into clinical benefit. The present review focuses on neuroprotective effects of anaesthetics and is based on the most recently published reports.

Journal Article↗

Propofol protects cultured brain cells from iron ion-induced death: comparison with trolox.

The anesthetic propofol (PPF) has been shown to be an antioxidant in acellular experiments. This study was designed to assess the ability of PPF to protect primary-cultured brain cells against iron-mediated toxicity. A comparison with trolox (TX), a hydrosoluble vitamin E analogue, was performed. Rat cortical cells were exposed to 10 microM FeSO(4), PPF and/or TX. After a 4-h incubation, PPF and TX improved cell survival (lactate dehydrogenase measurements) in a concentration-dependent manner. The respective EC(50s) of each substance were 4 and 4.6 microM. The maximal effect was obtained at a 25-microM concentration which is similar to concentrations of PPF used clinically. The combination of both drugs at certain concentrations showed a complete protection of the cells, a significant decrease in intracellular peroxide production (dichloro-fluorescein diacetate (DCF-DA) fluorescence, 4-h incubation), in lipoperoxidation (thiobarbituric acid reactive substances fluorescence, PPF 6.25 microM+TX 12.5 microM) and an additive protective effect. This was true after 4- and 16-h incubation. These data suggest that PPF is neuroprotective. Moreover, the combination with a vitamin E analogue confers long duration protection against oxidative stress.

Animals↗

[Management of severely head-injured patients during the first 24 hours. Which specific therapeutics?].

Intracranial and systemic mechanisms of the secondary brain lesion are the targets of specific therapy for the head-injured patient. Recommendations for good clinical practice have recently defined the role of the main therapeutic measures. There is no indication for corticosteroids in head injury. Mannitol is the first-choice therapy for increased intracranial pressure, and barbiturates are still considered as a rescue therapy in case of refractory intracranial hypertension. The place of hypothermia remains to be defined. Although controversial, optimized hyperventilation, induced systemic hypertension and vasoconstrictive therapy are optimally used under multimodal monitoring. New therapeutic perspectives, aimed at controlling biochemical disorders at a cellular level, are under investigation, but are still inconclusive at the present time.

Barbiturates↗

Target-controlled infusion of propofol and remifentanil combined with bispectral index monitoring for awake craniotomy.

We describe the target-controlled administration of propofol and remifentanil, combined with monitoring of the bispectral index, during an awake craniotomy for removal of a left temporo-parietal tumour near the motor speech centre. Target concentrations of the two drugs were adjusted according to the patient's responses to painful stimuli and surgical events, and the need for speech testing. Allowing the effect-site concentrations of propofol and remifentanil to decrease during surgery allowed the performance of cortical speech mapping and the testing of the patient's ability to speak. Although the bispectral index was not used as a guide for the administration of the drugs, its value correlated better with the patient's responsiveness than did the predicted effect-site concentrations of propofol. Side-effects, comprising hypotension, respiratory depression and airway obstruction, were related to rapid increases in drug infusion rates and were easily managed.

Analgesia↗

Effects of propofol on endothelial cells subjected to a peroxynitrite donor (SIN-1).

We investigated the effect of propofol on endothelial cells subjected to the peroxynitrite (ONOO-) donor 3-morpholino sydnonimine (SIN-1). Cells were incubated overnight with 0.5, 1.0 or 2.0 mM SIN-1, with or without 10-3 M propofol (Diprivan). Cytotoxicity, assessed by measuring the release of pre-incorporated 51Cr, increased when the concentration of SIN-1 increased, and was significantly decreased by 10-3 M propofol (90%, 78% and 28% of protection against 0.5, 1.0 and 2.0 mM SIN-1, respectively). Cell protection against 1 mM SIN-1 was tested with 0.03-1.0 mM propofol and this was compared to tyrosine, a target molecule for peroxynitrite. Propofol protected cells in a dose-dependent manner (r = 0.98; p < 0.001) and was as effective as tyrosine. Finally, using high-performance liquid chromatography, we demonstrated that propofol reacted with ONOO- more rapidly than did tyrosine, inhibiting nitrotyrosine formation. In the absence of propofol, 3.5 mM ONOO- with 1 mM tyrosine yielded 39.6% nitrotyrosine, but nitrotyrosine was not produced when 5 mM propofol was added. We conclude that propofol protects endothelial cells against the toxicity of ONOO-. The anti-oxidant properties of propofol can be partially attributed to its scavenging effect on peroxynitrite, a property that might be relevant in pathological situations involving a significant contribution of peroxynitrite to tissue damage.

Anesthetics, Intravenous↗

Evaluation of acute normovolemic hemodilution for surgical repair of craniosynostosis.

This clinical report investigated the potential benefit of acute normovolemic hemodilution (ANH) as a blood-saving technique in the surgical repair of craniosynostosis. Over a 4-year period, 34 healthy children undergoing surgical repair of scaphocephaly or pachycephaly were randomly assigned to two groups of 17 patients each. Patients of the first group (ANH group) were submitted to ANH (target Ht: 25%) immediately before surgery and patients of the second group (Control group) were not. During surgery, estimated blood loss was compensated with a 5% albumin solution and no autologous or homologous blood was transfused. At the end of surgery, intraoperative blood loss (mean +/- SD) calculated on the basis of the Ht value and the children weight was 21.3+/-8% of the estimated blood volume (EBV) in the ANH group and 24+/-6.6% in the Control group. Children of the ANH group received their autologous blood (18.9+/-3.3% of EBV) systematically at the end of surgery. In the postoperative period, homologous blood was transfused when the Ht value was equal or less than 21%. Both groups were comparable regarding age, weight, type of craniosynostosis, duration of surgery, EBV, and preoperative Ht value. No difference was observed between ANH and Control groups in the number of patients who received homologous blood (15/17 and 14/17, respectively), in the amount of homologous blood transfused (17+/-4.7% and 19.6+/-6.3% of the EBV, respectively), and in the Ht value before hospital discharge (29.4+/-5.0% and 30.7+/-4.9%, respectively). In conclusion, this report suggests that ANH reduces neither the incidence of homologous transfusion nor the amount of homologous blood transfused in this series of children undergoing surgical repair of craniosynostosis.

Albumins↗

Effects of ephedrine on the onset time of neuromuscular block and intubating conditions after cisatracurium: preliminary results.

We studied the effects of intravenous ephedrine on the onset time and the intubating conditions 2 min after a bolus dose of cisatracurium (0.15 mg kg-1). Thirty patients anaesthetized with sufentanil and propofol were randomly divided in 2 groups to receive either ephedrine (70 micrograms.kg-1) or saline, 5 s before propofol. Cisatracurium was administered after loss of consciousness. Neuromuscular block was assessed at the adductor pollicis using accelography. Tracheal intubation was performed 2 min after cisatracurium injection and rated as excellent, good, poor or bad. At intubation, neuromuscular block (% height of control T1) was greater in patients receiving ephedrine (36.1 +/- 25.8% vs 57.9 +/- 25.1%) (mean +/- SD). The frequency of excellent intubating conditions was higher after ephedrine (86.6%) than after saline (40.0%). The onset time of cisatracurium was shorter after ephedrine (167 +/- 64.8 s vs 234.9 +/- 63.1 s). Thus, a low dose of ephedrine given before induction of anaesthesia improves the intubating conditions 2 min after 0.15 mg kg-1 cisatracurium and this effect likely relates to a quicker onset of neuromuscular block.

Adult↗

Effects of mild hypothermic cardiopulmonary bypass on EEG bispectral index.

We studied the effect of mild hypothermic cardiopulmonary bypass (30 degrees C) on the EEG Bispectral Index in 10 patients undergoing elective CABG. BIS was recorded at 11 event-related time points during the procedure. After a significant decrease at the induction of anaesthesia, BIS was not further modified during the procedure. BIS was neither affected by surgical stimulation nor by CPB and mild hypothermia. We conclude that we did not find any reason to preclude the use of BIS to assess the hypnotic effects of anaesthetics during normothermic or mild hypothermic CPB.

Aged↗

[Evaluation of cerebral metabolism].

The brain requires high amounts of energy for cellular homeostasis and neurological functions. This energy is mainly supplied by the oxidation of glucose, although other substrates may be used in critical situations. The capacity of the brain to conserve energy is illustrated by flow metabolism coupling, and by the separation between functional and basal activity. The evaluation of cerebral metabolism is defined as the assessment of energy substrates availability and utilization. This evaluation may be performed in physiological or pathological conditions, at a regional or at the global level, at rest or during activation processes. The main techniques discussed in this review include monitoring of venous blood in the jugular bulb, cerebral microdialysis, near infrared spectroscopy, cerebral oximetry using microprobe electrodes, positron emission tomography, magnetic resonance and the magnetoencephalography.

Animals↗

Influence of induction of anaesthesia on intubating conditions one minute after rocuronium administration: comparison of ketamine and thiopentone.

We compared the effect of thiopentone and ketamine on intubating conditions after rocuronium 0.6 mg.kg-1 in two groups of patients (n = 16 each), aged 21-44 years, undergoing elective surgery. Premedication consisted of alprazolam 1 mg by mouth 1 h before surgery. All patients received midazolam 2 mg intravenously 2 min before intravenous administration of thiopentone 5 mg.kg-1 or ketamine 2.5 mg.kg-1. Muscle relaxation was provided by rocuronium 0.6 mg.kg-1. One minute after rocuronium administration, tracheal intubation was performed within 15 s by a skilled anaesthetist blinded to the treatment group assignment. Intubating conditions were graded as excellent, good, fair or poor on the basis of jaw relaxation, position of vocal cords and diaphragmatic response. Neuromuscular transmission was assessed at the adductor pollicis muscle using a TOF-GUARD monitor. Excellent and good intubating conditions were obtained in 100% of patients in the ketamine group and in 50% of patients in the thiopentone group (p = 0.002). Jaw relaxation was similar in both groups but vocal cord conditions were better and the diaphragmatic response less marked in the ketamine group compared with the thiopentone group (p = 0.002). The degree of neuromuscular block [% decrease of T1, mean (SD)] at the time of intubation was similar: 51.8 (25)% (ketamine group) and 54.3 (23.1)% (thiopentone group). We conclude that ketamine 2.5 mg.kg-1 provides better intubating conditions than thiopentone 5 mg.kg-1 1 min after administration of rocuronium 0.6 mg.kg-1.

Adult↗

Effect of epidural bupivacaine on the relationship between the bispectral index and end-expiratory concentrations of desflurane.

We compared the relationship between the bispectral index and end-tidal desflurane concentrations in 20 patients undergoing elective surgery. Patients received epidurally either 10 ml saline (group S) or 10 ml bupivacaine 0.125% with epinephrine 1/800 000 (group B) before induction of anaesthesia with sufentanil (0.15 microgram.kg(-1)) and propofol (2 mg.kg(-1)); muscle relaxation was obtained with cisatracurium (0.2 mg.kg(-1)). Patients lungs were ventilated to maintain end-tidal desflurane at 3% in O2/N2O (50/50) until 5 min after skin incision, followed by two consecutive 10 min periods at end-tidal desflurane 6% and 9%. bispectral index values were recorded before induction, at 3% desflurane before and 5 min after skin incision, and at 6% and 9% end-tidal desflurane. Bispectral index decreased with increasing end-tidal desflurane concentration (ANOVA: p < 0.05). The decrease in bispectral index was significant between pre-induction, 3% and 6% desflurane. No significant difference was observed at 3% desflurane before and after skin incision, or between 6 and 9% desflurane. The relationship between bispectral index and end-tidal desflurane concentration was fitted by a linear regression in each group. No significant difference in bispectral index was observed between the groups at any time. We conclude that bispectral index decreases with increasing desflurane concentration and that this relationship is not affected by epidural 0.125% bupivacaine.

Adolescent↗

Effects of two calculated plasma sufentanil concentrations on the hemodynamic and bispectral index responses to Mayfield head holder application.

The effects of two calculated plasma sufentanil (SUF) concentrations on the hemodynamic and bispectral index (BIS) responses to Mayfield head holder (MH) application were studied in 20 patients scheduled for intracranial surgery. Premedication consisted of hydroxyzine, alprazolam, and atropine given orally 1 hour before surgery. Anesthesia was provided with propofol (PPF) and SUF using a target-controlled infusion device. Patients were randomly assigned to one of two groups according to calculated plasma concentrations: 3 microg/mL(-1) of PPF and 0.5 ng/mL(-1) of SUF in group I (GI) and 3 microg/mL(-1) of PPF and 1 ng/mL(-1) of SUF in group II (GII). The MH was fixed 33.0+/-6.6 minutes (mean +/- SD) after induction. Systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) as well as heart rate (HR) and BIS were recorded 1 minute before pinning (baseline) as well as 1 minute (P1), 2 minutes (P2), and 3 minutes (P3) after pinning. Multivariate repeat-measured analyses of variance were applied to the baseline-subtracted measurements of hemodynamic and BIS values. Groups were compared using the Student's t test, and P < .05 was considered to be statistically significant. Patients' characteristics, baseline hemodynamic values, and BIS values were similar in both groups. A significant overall time effect was observed for all variables, but no significant overall SUF effect was detected. Increases in SAP, MAP, DAP, and HR did not differ significantly between groups. The increase in hemodynamic variables did not exceed 20% of baseline value in either group. In contrast, at P1, the increase in BIS over the baseline value was significantly higher in GI (15.0+/-7.9) than in GII (6.7+/-6.5). In conclusion, MH application was associated with a significant, although not clinically relevant, increase in hemodynamic variables whatever the calculated plasma SUF concentration (0.5 or 1.0 ng/mL(-1)). In contrast, the increase in BIS observed at pinning was significantly higher in patients with the lowest calculated plasma SUF concentrations. This suggests that the BIS response to noxious stimulation is modulated by the analgesic regimen.

Alprazolam↗

Comparison of three-dimensional visualization techniques for depicting the scala vestibuli and scala tympani of the cochlea by using high-resolution MR imaging.

BACKGROUND AND PURPOSE: Cochlear implantation requires introduction of a stimulating electrode array into the scala vestibuli or scala tympani. Although these structures can be separately identified on many high-resolution scans, it is often difficult to ascertain whether these channels are patent throughout their length. The aim of this study was to determine whether an optimized combination of an imaging protocol and a visualization technique allows routine 3D rendering of the scala vestibuli and scala tympani. METHODS: A submillimeter T2 fast spin-echo imaging sequence was designed to optimize the performance of 3D visualization methods. The spatial resolution was determined experimentally using primary images and 3D surface and volume renderings from eight healthy subjects. These data were used to develop the imaging sequence and to compare the quality and signal-to-noise dependency of four data visualization algorithms: maximum intensity projection, ray casting with transparent voxels, ray casting with opaque voxels, and isosurface rendering. The ability of these methods to produce 3D renderings of the scala tympani and scala vestibuli was also examined. The imaging technique was used in five patients with sensorineural deafness. RESULTS: Visualization techniques produced optimal results in combination with an isotropic volume imaging sequence. Clinicians preferred the isosurface-rendered images to other 3D visualizations. Both isosurface and ray casting displayed the scala vestibuli and scala tympani throughout their length. Abnormalities were shown in three patients, and in one of these, a focal occlusion of the scala tympani was confirmed at surgery. CONCLUSION: Three-dimensional images of the scala vestibuli and scala tympani can be routinely produced. The combination of an MR sequence optimized for use with isosurface rendering or ray-casting algorithms can produce 3D images with greater spatial resolution and anatomic detail than has been possible previously.

Adult↗

The application of three-dimensional magnetic resonance imaging rendering of the inner ear in assessment for cochlear implantation.

OBJECTIVE: To study the use of three-dimensional (3D) rendering of T2-weighted magnetic resonance imaging (MRI) images into 3D models of the inner ear in the preoperative assessment for cochlear implantation. STUDY DESIGN: A retrospective case review of cochlear implant candidates undergoing preoperative imaging studies to determine their suitability for surgical implantation. SETTING: A tertiary referral center for the northwest area of England with an established 10-year-old program in cochlear implantation. PATIENTS: Selected adult and pediatric patients referred for cochlear implant assessment from 1996 to 1998, who underwent computerized tomography (CT) and MRI studies. INTERVENTION: Diagnostic imaging modality to assess the structure and patency of the inner ear. MAIN OUTCOME MEASURES: To see how detailed anatomic information provided by these 3D models influenced surgical decisions. RESULTS: Four case studies (with their 3D models) are presented to illustrate different points of interest. CONCLUSION: These 3D models provide the implanting surgeon with precise, detailed, and easily interpretable information about the cochlea, which help to guide surgical implantation, or in certain cases, to decide against attempting surgery in the presence of unfavorable anatomic factors.

Child↗

Propofol reacts with peroxynitrite to form a phenoxyl radical: demonstration by electron spin resonance.

Peroxynitrite (ONOO-), resulting from the reaction of nitric oxide with superoxide anion, is a powerful oxidant produced in activated macrophages, during ischemia-reperfusion processes as well as in neurodegenerative disorders. This study investigated the reaction of the anesthetic agent propofol (PPF) with ONOO-, using electron spin resonance (ESR) and UV-visible spectrometry. Peroxynitrite was synthetized either from acidified hydrogen peroxide and nitrite, or from sodium azide and ozone. The addition of ONOO- to PPF in alkaline solution (pH 12) allowed to detect a, short lifetime, ESR signal corresponding to a phenoxyl radical. This finding was confirmed by a UV-visible study, resulting in the appearance of 427 nm peak and the disappearance of the peak located at 239 nm. The 291 nm peak remained unchanged. The identification of the end-product of the reaction of PPF with ONOO- needs further investigations.

Anesthetics↗

Protective activity of propofol, Diprivan and intralipid against active oxygen species.

We separately studied the antioxidant properties of propofol (PPF), Diprivan (the commercial form of PPF) and intralipid (IL) (the vehicle solution of PPF in Diprivan) on active oxygen species produced by phorbol myristate acetate (10(-6) M)-stimulated human polymorphonuclear leukocytes (PMN: 5 x 10(5) cells/assay), human endothelial cells (5 x 10(5) cells/assay) or cell-free systems (NaOCl or H2O2/peroxidase systems), using luminol (10(-4) M)-enhanced chemiluminescence (CL). We also studied the protective effects of Diprivan on endothelial cells submitted to an oxidant stress induced by H2O2/MPO system: cytotoxicity was assessed by the release of preincorporated 51Cr. Propofol inhibited the CL produced by stimulated PMN in a dose dependent manner (until 5 x 10(-5) M, a clinically relevant concentration), while Diprivan and IL were not dose-dependent inhibitors. The CL produced by endothelial cells was dose-dependently inhibited by Diprivan and PPF, and weakly by IL (not dose-dependent). In cell free systems, dose-dependent inhibitions were obtained for the three products with a lower effect for IL. Diprivan efficaciously protected endothelial cells submitted to an oxidant stress, while IL was ineffective. By HPLC, we demonstrated that PPF was not incorporated into the cells. The drug thus acted by scavenging the active oxygen species released in the extracellular medium. IL acted in the same manner, but was a less powerful antioxidant.

Antioxidants↗

Effects of target-controlled anesthesia with propofol and sufentanil on the hemodynamic response to Mayfield head holder application.

The effects of target-controlled anesthesia with propofol and sufentanil on the hemodynamic response to Mayfield head holder (MH) application were evaluated in 18 ASA I and II patients undergoing scheduled intracranial surgery. Premedication consisted of hydroxyzine, alprazolam and atropine given orally 1 h before surgery. Anesthesia was provided with propofol and sufentanil using a target-controlled infusion device; constant calculated plasma concentrations of 4 micrograms ml-1 propofol and 0.5 ng ml-1 sufentanil were maintained throughout the study. Muscle relaxation was obtained with atracurium and ventilation was controlled with air/oxygen. The MH was fixed 45 +/- 12 min (mean +/- SD) after induction of anesthesia. Heart rate and systolic, diastolic, and mean non invasive arterial pressure were monitored and recorded 5 min before induction of anesthesia (control), 1 min before MH application (MH-1), at MH application, and 1 and 2 min after MH application. Systolic, diastolic, mean arterial pressure, and heart rate increased significantly during and after MH application when compared with MH-1 values, but remained constantly lower than control. Hemodynamic parameters measured 1 min before MH application were significantly lower than control. The results of the study indicate that target-controlled anesthesia maintained with constant calculated plasma concentrations of 4 micrograms ml-1 propofol and 0.5 ng ml-1 sufentanil prevents the increase in arterial pressure and heart rate beyond control values following MH application but may induce some degree of arterial hypotension in the absence of nociceptive stimulation.

Adjuvants, Anesthesia↗