Neurochemical profile of the developing mouse cortex determined by in vivo 1H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia.

The neurochemical profile of the cortex develops in a region and time specific manner, which can be distorted by psychiatric and other neurological pathologies. Pre-clinical studies often involve experimental mouse models. In this study, we determined the neurochemical profile of C57BL/6 mice in a longitudinal study design to provide a reference frame for the normal developing mouse cortex. Using in vivo proton NMR spectroscopy at 14 T, we measured the concentrations of 18 metabolites in the anterior and posterior cortex on postnatal days (P) 10, 20, 30, 60 and 90. Cortical development was marked by alterations of highly concentrated metabolites, such as N-acetylaspartate, glutamate, taurine and creatine. Regional specificity was represented by early variations in the concentration of glutamine, aspartate and choline. In adult animals, regional concentration differences were found for N-acetylaspartate, creatine and myo-inositol. In this study, animals were exposed to recurrent isoflurane anaesthesia. Additional experiments showed that the latter was devoid of major effects on behaviour or cortical neurochemical profile. In conclusion, the high sensitivity and reproducibility of the measurements achieved at 14 T allowed us to identify developmental variations of cortical areas within the mouse cortex.

Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychosocial support: a randomised clinical trial.

BACKGROUND: While detoxification under anaesthesia accelerates the detoxification procedure, there is a lack of randomised clinical trials evaluating its effectiveness compared to traditional detoxification procedures, and a lack of data on long-term abstinence. METHODS: Prospective randomised clinical trial. Analysis by intention to treat and per protocol. Setting: Specialised substance abuse unit in a psychiatric teaching hospital and an intensive care unit of a general hospital. Participants: Seventy patients with opiate mono-dependence requesting detoxification: 36 randomised to RODA (treatment as allocated received by 26) and 34 randomised to classical clonidine detoxification (treatment as allocated received by 21). Main outcome measures: Successful detoxification, safety and self-reported abstinence at 3, 6 and 12 months after detoxification. RESULTS: Socio-demographics were similar in both groups at baseline. No complications were reported during or after anaesthesia. According to the intention to treat analysis, 28/36 (78%) RODA patients and 21/34 (62%) of the clonidine group successfully completed the detoxification process (p=0.14). In the intention to treat analysis, 30% of RODA patients were abstinent after 3 months compared to 14% in the clonidine group (p=0.11). No difference was found at 6 and 12 months (both groups showed less than 5% abstinence after 12 months). The per-protocol analysis showed similar results with no statistical differences either for ASI mean scores or for the SF36 questionnaire. CONCLUSION: Although the detoxification success rate and abstinence after 3 months were slightly better for the RODA procedure compared to clonidine treatment, these differences were not statistically significant and disappeared completely after 6 and 12 months.

The influence of drugs used in cardiac anaesthesia and critical care on multiple electrode aggregometry: an in-vitro volunteer study.

BACKGROUND: Multiple electrode aggregometry (MEA) is a point-of-care test evaluating platelet function and the efficacy of platelet inhibitors. In MEA, electrical impedance of whole blood is measured after addition of a platelet activator. Reduced impedance implies platelet dysfunction or the presence of platelet inhibitors. MEA plays an increasingly important role in the management of perioperative platelet dysfunction. In vitro, midazolam, propofol, lidocaine and magnesium have known antiplatelet effects and these may interfere with MEA interpretation. OBJECTIVE: To evaluate the extent to which MEA is modified in the presence of these drugs. DESIGN: An in-vitro study using blood collected from healthy volunteers. SETTING: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 2010 to 2011. PATIENTS: Twenty healthy volunteers. INTERVENTION: Measurement of baseline MEA was using four activators: arachidonic acid, ADP, TRAP-6 and collagen. The study drugs were then added in three increasing, clinically relevant concentrations. MAIN OUTCOME MEASURE: MEA was compared with baseline for each study drug. RESULTS: Midazolam, propofol and lidocaine showed no effect on MEA at any concentration. Magnesium at 2.5 mmol l had a significant effect on the ADP and TRAP tests (31 ± 13 and 96 ± 39 AU, versus 73 ± 21 and 133 ± 28 AU at baseline, respectively), and a less pronounced effect at 1 mmol l on the ADP test (39 ± 0 AU). CONCLUSION: Midazolam, propofol and lidocaine do not interfere with MEA measurement. In patients treated with high to normal doses of magnesium, MEA results for ADP and TRAP-tests should be interpreted with caution. TRIAL REGISTRATION: Clinicaltrials.gov (no. NCT01454427).

Incidents occuring during anesthesia for total hip arthroplasty: a comparison of general versus regional anaesthesia

Background: The type of anesthesia to be used for total hip arthroplasty (THA) is still a matter of debate. We compared the occurrence of per- and post-anesthesia incidents in patients receiving either general (GA) or regional anesthesia (RA). Methods: We used data from 29 hospitals, routinely collected in the Anaesthesia Databank Switzerland register between January 2001 and December 2003. We used multi-level logistic regression models. Results: There were more per- and post-anesthesia incidents under GA compared to RA (35.1% vs 32.7 %, n = 3191, and 23.1% vs 19.4%, n = 3258, respectively). In multi-level logistic regression analysis, RA was significantly associated with a lower incidence of per-anesthetic problems, especially hypertension, compared with GA. During the post-anesthetic period, RA was also less associated with pain. Conversely, RA was more associated with post-anesthetic hypotension, especially for epidural technique. In addition, age and ASA were more associated with incidents under GA compared to RA. Men were more associated with per-anesthetic problems under RA compared to GA. Whereas increased age (>67), gender (male), and ASA were linked with the choice of RA, we noticed that this choice depended also on hospital practices after we adjusted for the other variables. Conclusions: Compared to RA, GA was associated with an increased proportion of per- and post-anesthesia incidents. Although this study is only observational, it is rooted in daily practice. Whereas RA might be routinely proposed, GA might be indicated because of contraindications to RA, patients' preferences or other surgical or anaesthesiology related reasons. Finally, the choice of a type of anesthesia seems to depend on local practices that may differ between hospitals.

Incidents occurring during anesthesia for total hip arthroplasty: a comparison of general versus regional anaesthesia

Background: The type of anesthesia to be used for total hip arthroplasty (THA) is still a matter of debate. We compared the occurrence of per- and post-anesthesia incidents in patients receiving either general (GA) or regional anesthesia (RA). Methods: We used data from 29 hospitals, routinely collected in the Anaesthesia Databank Switzerland register between January 2001 and December 2003. We used multi-level logistic regression models. Results: There were more per- and post-anesthesia incidents under GA compared to RA (35.1% vs 32.7 %, n = 3191, and 23.1% vs 19.4%, n = 3258, respectively). In multi-level logistic regression analysis, RA was significantly associated with a lower incidence of per-anesthetic problems, especially hypertension, compared with GA. During the post-anesthetic period, RA was also less associated with pain. Conversely, RA was more associated with post-anesthetic hypotension, especially for epidural technique. In addition, age and ASA were more associated with incidents under GA compared to RA. Men were more associated with per-anesthetic problems under RA compared to GA. Whereas increased age (>67), gender (male), and ASA were linked with the choice of RA, we noticed that this choice depended also on hospital practices after we adjusted for the other variables. Conclusions: Compared to RA, GA was associated with an increased proportion of per- and post-anesthesia incidents. Although this study is only observational, it is rooted in daily practice. Whereas RA might be routinely proposed, GA might be indicated because of contraindications to RA, patients' preferences or other surgical or anaesthesiology related reasons. Finally, the choice of a type of anesthesia seems to depend on local practices that may differ between hospitals.

Retinal embolisation with localised retinal detachment following retrobulbar anaesthesia.

BACKGROUND: The aim of this communication is to describe an unusual and serious complication of retrobulbar anaesthesia for cataract surgery. HISTORY AND SIGNS: A 78-year-old female was referred for visual loss (light perception) 24 hours after apparently uneventful cataract surgery with retrobulbar anaesthesia in her left eye. Fundus examination revealed multiple arterial emboli and a localised retinal detachment. MRI revealed a retrobulbar hypersignal of the optic nerve associated with perineuritis. The cardiovascular examination was normal. We assumed this condition resulted from injection of the anaesthetic mixture into the optic nerve. THERAPY AND OUTCOME: In order to improve retinal circulation and oxygenation, the intraocular pressure was maximally lowered and anticalcic therapy administered, expecting optimal arterial dilatation. Methylprednisolone (1 g/day 3 days i. v., then rapidly tapered) was also added. The retina slowly reattached but visual acuity remained unchanged. CONCLUSIONS: Retrobulbar anaesthesia is routinely used for ocular surgery. Serious complications may still happen, however. This case adds to the previously reported spectrum of complications from retrobulbar anaesthesia.

Evolution of anaesthesia care and related events between 1996 and 2010 in Switzerland.

BACKGROUND: Anaesthesia Databank Switzerland (ADS) is a voluntary data registry introduced in 1996. Its ultimate goal is to promote quality in anaesthesiology. METHODS: The ADS registry analyses routinely recorded adverse events and provides benchmark comparisons between anaesthesia departments. Data collection comprises a set of 31 variables organised into three modules, one mandatory and two optional. RESULTS: In 2010, the database included 2,158,735 anaesthetic procedures. Over time, the proportions of older patients have increased, the largest group being aged 50-64 years. The percentage of patients with American Society of Anesthesiologists (ASA) status 1 has decreased while the percentage of ASA status 2 or 3 patients has increased. The most frequent comorbidities recorded were hypertension (21%), smoking (16%), allergy (15%) and obesity (12%). Between 1996 and 2010, 125,579 adverse events were recorded, of which 34% were cardiovascular, 7% respiratory, 39% technical and 20% non-specific. The most severe events were resuscitation (50%), oliguria (22%), myocardial ischaemia (17%) and haemorrhage (10%). CONCLUSION: Routine ADS data collection contributes to the monitoring of trends in anaesthesia care in Switzerland. The ADS system has proved to be usable in daily practice, although this remains a constant challenge that is highly dependent on local quality management and quality culture. Nevertheless, success in developing routine regular feedback to users to initiate discussions about anaesthetic events would most likely help strengthen departmental culture regarding safety and quality of care.

Antagonism of neuromuscular blockade but not muscle relaxation affects depth of anaesthesia

RÉSUMÉ Introduction L'effet des agents myorelaxants ainsi que des anticholinestérases sur la profondeur d'anesthésie a été étudié avec des résultats contradictoires. C'est pourquoi nous avons évalué l'effet de l'atracurium et de la néostigmine sur le BIS (bispectral index) ainsi que sur les potentiels auditives évoqués (middle-latency auditory evoked potentials, A-Line® autoregressive index [AAI]). Méthodes Après avoir obtenu l'accord du comité d'éthique local, nous avons étudié 40 patients ayant donné leur consentement écrit, ASA I-II, âgé de 18-69 ans. L'anesthésie générale a consisté en anesthésie intra-veineuse à objectif de concentration avec du propofol et du remifentanil. La fonction de la jonction neuromusculaire était monitorée en continu au moyen d'un électromyographe. Le BIS et l'AAI ont été enregistrés en continu. Après avoir atteint des valeurs stables au niveau du BIS, les patients ont été attribués à deux groupes par randomisation. Les patients du groupe 1 ont reçu 0.4 mg kg-1 d'atracurium et 5 minutes plus tard le même volume de NaCI 0.9%, dans le groupe 2 la séquence d'injection était inversée, le NaCI 0.9% en premier et l'atracurium en deuxième. Au moment où le premier « twitch » d'un train de quatre atteignait 10% de l'intensité avant la relaxation, les patients ont été randomisés une deuxième fois. Les patients du groupe N ont reçu 0.04 mg kg-1 de néostigmine et 0.01 rn9 kg-1 de glycopyrrolate alors que le groupe contrôle (G) ne recevait que 0.01 mg kg-] de glycopyrrolate. Résultats : L 'injection d'atracurium ou de NaCI 0.9% n'a pas eu d'effet sur le BIS ou l'AAI. Après l'injection de néostigmine avec glycopyrrolate, le BIS et I `AAI a augmenté de manière significative (changement maximal moyen du BIS 7.1 ± 7.5, P< 0.001, de l'AAI 9.7 ± 10.5, P< 0.001). Suite à l'injection de glycopyrrolate seule, le BIS et l'AAI a augmenté également (changement maximal moyen du BIS 2.2 ± 3.4, P< 0.008, de l'AAI 3.5 ± 5.7, P< 0.012), mais cette augmentation était significativement moins importante que dans le groupe N (P< 0.012 pour le BIS, P< 0.027 pour l'AAI). Conclusion Ces résultats laissent supposer que la néostigmine peut altérer la profondeur de l'anesthésie. La diminution de la profondeur d'anesthésie enregistrée par le BIS et l'AAI correspond probablement à une réapparition brusque d'une stimulation centrale liée à la proprioception. Au contraire, lors de la curarisation, le tonus musculaire diminue de manière beaucoup plus progressive, pouvant ainsi expliquer l'absence d'effet sur la profondeur d'anesthésie. ABSTRACT Background. Conflicting effects of neuromuscular blocking drugs and anticholinesterases on depth of anaesthesia have been reported. Therefore we evaluated the effect of atracurium and neostigmine on bispectral index (BIS) and middle-latency auditory evoked potentials (AAI). Methods. We studied 40 patients (ASA I-II) aged 18-69 yr. General anaesthesia consisted of propofol and remifentanil by target-controlled infusion and neuromuscular function was monitored by electromyography. When BIS reached stable values, patients were randomly assigned to one of two groups. Group I received atracurium 0.4 mg kg-1 and, 5 min later, the same volume of NaCl 0.9%; group 2 received saline first and then atracurium. When the first twitch of a train of four reached 10% of control intensity, patients were again randomized: one group (N) received neostigmine 0.04 mg kg-1 and glycopyrrolate 0.01 mg kg-1, and the control group (G) received only glycopyrrolate. Results. Injection of atracurium or NaCl 0.9% had no effect on BIS or AAI. After neostigmine¬glycopyrrolate, BIS and AAI increased significantly (mean maximal change of BIS 7.1 [SD 7.5], P<0.001; mean maximal change of AAI 9.7 [10.5], P<0.001). When glycopyrrolate was injected alone BIS and AAI also increased (mean maximal change of BIS 2.2 [3.4], P=0.008; mean maximal change of AAI 3.5 [5.7], P=0.012), but this increase was significantly less than in group N (P=0.012 for BIS; P=0.027 for AAI). Conclusion. These data suggest that neostigmine alters the state of propofol-remifentanil anaesthesia and may enhance recovery.

Report on initial experience with local anaesthesia for carotid artery endarterectomy.

PURPOSE OF THE STUDY: This prospective study reports our preliminary results with local anaesthesia (LA) for carotid endarterectomy (CEA). MATERIAL AND METHODS: Twenty CEA in nineteen patients were performed using a three-stage local infiltration technique. CEA were performed through a short Duplex-assisted skin incision (median length: 55 mm) using a retro-jugular approach and polyurethane patch closure (median length: 35 mm). RESULTS: There were 13 men and 6 women with a mean age of 71.2 years. The indications of CEA were asymptomatic lesions in 11 cases, stroke in 7 cases and transient ischaemic attack in 2 cases. The median degree of internal carotid artery stenosis was 90%. One patient (5%) required an intraluminal shunt. There were no peri-operative deaths, stroke or conversion to general anaesthesia (GA). The median length of stay was 3 days. CONCLUSIONS: LA is a good alternative to GA. It can be used after a feasibility study and a short teaching procedure. In our centre, it is a safe and effective procedure associated with low morbidity, high acceptance by patients and a short hospital stay.

Auditory stimulation does not induce implicit memory during anaesthesia

Background and aim of the study: Formation of implicit memory during general anaesthesia is still debated. Perceptual learning is the ability to learn to perceive. In this study, an auditory perceptual learning paradigm, using frequency discrimination, was performed to investigate the implicit memory. It was hypothesized that auditory stimulation would successfully induce perceptual learning. Thus, initial thresholds of the frequency discrimination postoperative task should be lower for the stimulated group (group S) compared to the control group (group C). Material and method: Eighty-seven patients ASA I-III undergoing visceral and orthopaedic surgery during general anaesthesia lasting more than 60 minutes were recruited. The anaesthesia procedure was standardized (BISR monitoring included). Group S received auditory stimulation (2000 pure tones applied for 45 minutes) during the surgery. Twenty-four hours after the operation, both groups performed ten blocks of the frequency discrimination task. Mean of the thresholds for the first three blocks (T1) were compared between groups. Results: Mean age and BIS value of group S and group C are respectively 40 } 11 vs 42 } 11 years (p = 0,49) and 42 } 6 vs 41 } 8 (p = 0.87). T1 is respectively 31 } 33 vs 28 } 34 (p = 0.72) in group S and C. Conclusion: In our study, no implicit memory during general anaesthesia was demonstrated. This may be explained by a modulation of the auditory evoked potentials caused by the anaesthesia, or by an insufficient longer time of repetitive stimulation to induce perceptual learning.

MRS glucose mapping and PET joining forces: re-evaluation of the lumped constant in the rat brain under isoflurane anaesthesia.

Although numerous positron emission tomography (PET) studies with (18) F-fluoro-deoxyglucose (FDG) have reported quantitative results on cerebral glucose kinetics and consumption, there is a large variation between the absolute values found in the literature. One of the underlying causes is the inconsistent use of the lumped constants (LCs), the derivation of which is often based on multiple assumptions that render absolute numbers imprecise and errors hard to quantify. We combined a kinetic FDG-PET study with magnetic resonance spectroscopic imaging (MRSI) of glucose dynamics in Sprague-Dawley rats to obtain a more comprehensive view of brain glucose kinetics and determine a reliable value for the LC under isoflurane anaesthesia. Maps of Tmax /CMRglc derived from MRSI data and Tmax determined from PET kinetic modelling allowed to obtain an LC-independent CMRglc . The LC was estimated to range from 0.33 ± 0.07 in retrosplenial cortex to 0.44 ± 0.05 in hippocampus, yielding CMRglc between 62 ± 14 and 54 ± 11 μmol/min/100 g, respectively. These newly determined LCs for four distinct areas in the rat brain under isoflurane anaesthesia provide means of comparing the growing amount of FDG-PET data available from translational studies.

The effect of positive airway pressure during pre-oxygenation and induction of anaesthesia upon duration of non-hypoxic apnoea

Résumé de l'étude. L'application d'une pression positive (PEEP) pendant la phase d'induction d'une anesthésie générale peut prévenir la formation d'atélectasies pulmonaires. Ceci pourrait permettre d'accroître la durée d'apnée non hypoxique par l'augmentation de la capacité pulmonaire résiduelle fonctionnelle (CRF). Nous avons étudié le bénéfice de l'application d'une PEEP durant la phase d'induction d'une anesthésie générale sur la durée d'apnée avant que la saturation périphérique en oxygène atteigne 90%. Quarante patients ASA I-II ont été randomisés en deux groupes distincts. - Dans le groupe PEEP (n=20), les patients ont été pré-oxygénés durant 5 minutes avec une Fi02 à l00% par l'intermédiaire d'un appareil de CPAP (6cmH2O). Après induction de l'anesthésie, les patients furent ventilés mécaniquement (PEEP 6cmH2O) durant 5 minutes supplémentaires. - Dans le groupe ZEEP (n=20), aucune pression positive (ni CPAP, ni PEEP) ne fut utilisée. La durée d'apnée pour atteindre une saturation périphérique de 90% fut mesurée. La durée d'apnée non hypoxique était plus longue dans le groupe PEEP par rapport au groupe ZEEP (599 +/- 135 s vs 470 +/- 150 s, p= 0,007). Nous concluons que l'application d'une pression positive durant la phase d'induction d'une anesthésie générale chez l'adulte prolonge la durée d'apnée non hypoxique de plus de 2 minutes.

Studies on Neuromuscular Blocking Agents and Their Antagonists During Anaesthesia

Neuromuscular blocking agents (NMBAs) are widely used in clinical anaesthesia and emergency medicine. Main objectives are to facilitate endotracheal intubation and to allow surgery by reducing muscle tone and eliminating sudden movements, which may otherwise lead to trauma and complications. The most commonly used NMBAs are non-depolarizing agents with a medium duration of action, such as rocuronium and cisatracurium. They bind to the acetylcholine receptors in the neuromuscular junction, thus inhibiting the depolarization of the postsynaptic (muscular) membrane, which is a prerequisite for muscle contraction to take place. Previously, it has been assumed that nitrous oxide (N2O), which is commonly used in combination with volatile or intravenous anaesthetics during general anaesthesia, has no effect on NMBAs. Several studies have since claimed that N2O in fact does increase the effect of NMBAs when using bolus administration of the relaxant. The effect of N2O on the infusion requirements of two NMBAs (rocuronium and cisatracurium) with completely different molecular structure and pharmacological properties was assessed. A closed-loop feedback controlled infusion of NMBA with duration of at least 90 minutes at a 90% level of neuromuscular block was used. All patients received total intravenous anaesthesia (TIVA) with propofol and remifentanil. In both studies the study group (n=35) received N2O/Oxygen and the control group (n=35) Air/Oxygen. There were no significant differences in the mean steady state infusion requirements of NMBA (rocuronium in Study I; cisatracurium in Study II) between the groups in either study. In Study III the duration of the unsafe period of recovery after reversal of rocuronium-induced neuromuscular block by using neostigmine or sugammadex as a reversal agent was analyzed. The unsafe period of recovery was defined as the time elapsed from the moment of no clinical (visual) fade in the train-of-four (TOF) sequence until an objectively measured TOF-ratio of 0.90 was achieved. The duration of these periods were 10.3 ± 5.5 and 0.3 ± 0.3 min after neostigmine and sugammadex, respectively (P < 0.001). Study IV investigated the possible effect of reversal of a rocuronium NMB by sugammadex on depth of anaesthesia as indicated by the bispectral index and entropy levels in thirty patients. Sugammadex did not affect the level of anaesthesia as determined by EEG-derived indices of anaesthetic depth such as the bispectral index and entropy.

Total intravenous anaesthesia with propofol-racemic ketamine and propofol-S-ketamine: a comparative study and haemodynamic evaluation in dogs undergoing ovariohysterectomy

Total intravenous anaesthesia (TIVA) with propofol and ketamine proved to be very satisfactory from a clinical point of view. This blind randomised controlled trial was designed to compare induction and maintenance of anaesthesia under continuous infusion of propofol-racemic ketamine (PRK) with that of propofol-S-ketamine (PSK) and evaluate their haemodynamic, metabolic and ventilatory effects. Seven female dogs undergoing ovariohysterectomy were involved in each group. Anaesthesia was induced: in Group PRK, with propofol (4.0mg kg-1) and racemic ketamine (2.0mg kg-1) intravenous (i.v.), followed by i.v. infusion of propofol (initial dose of 0.5mg kg-1 min-1) and racemic ketamine (0.2mg kg-1 min-1); in Group PSK, with propofol (4.0mg kg-1) and S-ketamine (1.0 mg kg¹) i.v., followed by i.v. infusion of propofol (initial dose of 0.5mg kg-1 min-1) and S-ketamine (0.1mg kg-1 min-1). Parameters were assessed before anaesthesia and in 6 time points after induction. In both groups, heart rate increased significantly at all time points. There was a slight decrease in systemic blood pressure, cardiac output and cardiac index in both groups. The systolic index decrease significantly and intense respiratory depression was observed in all groups, making assisted ventilation necessary.