Pascal Meuret

Brain Mechanisms of Propofol-Induced Loss of Consciousness in Humans: a Positron Emission Tomographic Study

In the present study, we used positron emission tomography to investigate changes in regional cerebral blood flow (rCBF) during a general anesthetic infusion set to produce a gradual transition from the awake state to unconsciousness. Five right-handed human volunteers participated in the study. They were given propofol with a computer-controlled infusion pump to achieve three stable levels of plasma concentrations corresponding to mild sedation, deep sedation, and unconsciousness, the latter defined as unresponsiveness to verbal commands. During awake baseline and each of the three levels of sedation, two scans were acquired after injection of an H215O bolus. Global as well as regional CBF were determined and correlated with propofol concentrations. In addition, blood flow changes in the thalamus were correlated with those of the entire scanned volume to determine areas of coordinated changes. In addition to a generalized decrease in global CBF, large regional decreases in CBF occurred bilaterally in the medial thalamus, the cuneus and precuneus, and the posterior cingulate, orbitofrontal, and right angular gyri. Furthermore, a significant covariation between the thalamic and midbrain blood flow changes was observed, suggesting a close functional relationship between the two structures. We suggest that, at the concentrations attained, propofol preferentially decreases rCBF in brain regions previously implicated in the regulation of arousal, performance of associative functions, and autonomic control. Our data support the hypothesis that anesthetics induce behavioral changes via a preferential, concentration-dependent effect on specific neuronal networks rather than through a nonspecific, generalized effect on the brain.

Physostigmine Reverses Propofol-induced Unconsciousness and Attenuation of the Auditory Steady State Response and Bispectral Index in Human Volunteers

BACKGROUND It is postulated that alteration of central cholinergic transmission plays an important role in the mechanism by which anesthetics produce unconsciousness. The authors investigated the effect of altering central cholinergic transmission, by physostigmine and scopolamine, on unconsciousness produced by propofol. METHODS Propofol was administered to American Society of Anesthesiologists physical status 1 (n = 17) volunteers with use of a computer-controlled infusion pump at increasing concentrations until unconsciousness resulted (inability to respond to verbal commands, abolition of spontaneous movement). Central nervous system function was assessed by use of the Auditory Steady State Response (ASSR) and Bispectral Index (BIS) analysis of electrooculogram. During continuous administration of propofol, reversal of unconsciousness produced by physostigmine (28 microgram/kg) and block of this reversal by scopolamine (8.6 microgram/kg) were evaluated. RESULTS Propofol produced unconsciousness at a plasma concentration of 3.2 +/- 0.8 (+/- SD) microgram/ml (n = 17). Unconsciousness was associated with reductions in ASSR (0.10 +/- 0.08 microV [awake baseline 0.32 +/- 0.18 microV], P < 0.001) and BIS (55.7 +/- 8.8 [awake baseline 92.4 +/- 3.9], P < 0.001). Physostigmine restored consciousness in 9 of 11 subjects, with concomitant increases in ASSR (0.38 +/- 0.17 microV, P < 0.01) and BIS (75.3 +/- 8.3, P < 0.001). In all subjects (n = 6) scopolamine blocked the physostigmine-induced reversal of unconsciousness and the increase of the ASSR and BIS (ASSR and BIS during propofol-induced unconsciousness: 0.09 +/- 0.09 microV and 58.2 +/- 7.5, respectively; ASSR and BIS after physostigmine administration: 0.08 +/- 0.06 microV and 56.8 +/- 6.7, respectively, NS). CONCLUSIONS These findings suggest that the unconsciousness produced by propofol is mediated at least in part via interruption of central cholinergic muscarinic transmission.

An Evaluation of the Cutaneous Distribution After Obturator Nerve Block

In 1973, Winnie et al. introduced the inguinal paravascular three-in-one block, which allegedly provides anesthesia of three nerves—the femoral, lateral cutaneous femoral, and obturator nerves—with a single injection. This concept was undisputed until the success of the obturator nerve block was reassessed by using evidence of adductor weakness rather than cutaneous sensory blockade, the latter being variable in its distribution and often absent. We performed this study, therefore, to evaluate the area of sensory loss produced by direct injection of local anesthetic around the obturator nerve. A selective obturator nerve block with 7 mL of 0.75% ropivacaine was performed in 30 patients scheduled for knee surgery. Sensory deficit and adductor strength were evaluated for 30 min by using sensory tests (cold and light-touch perception) and the pressure generated by the patient’s squeezing a blood pressure cuff placed between the knees. Subsequently, a three-in-one block was performed, and the sensory deficit was reassessed. The obturator nerve block was successful in 100% of cases. The strength of adductors decreased by 77% ± 17% (mean ± sd). In 17 patients (57%), there was no cutaneous contribution of the obturator nerve. The remaining 7 patients (23%) had an area of hypoesthesia (cold sensation was blunt but still present) on the superior part of the popliteal fossa, and the other 6 (20%) had sensory deficit located at the medial aspect of the thigh. The three-in-one block resulted in blockade of the lateral aspect of the thigh in 87% of cases, whereas the anteromedial aspect was always anesthetized. By use of magnetic resonance imaging in eight volunteers, we demonstrated that the obturator nerve has already divided into its two branches at the site of local anesthetic injection. However, the injection of blue dye after having simulated the technique in five cadavers showed that the fluid regularly spread to both branches. We conclude that after three-in-one block, a femoral nerve block may have been assessed as an obturator nerve block in 100% of cases when testing the cutaneous distribution of the obturator nerve on the medial aspect of the thigh.

Auditory steady-state response and bispectral index for assessing level of consciousness during propofol sedation and hypnosis.

We assessed the effect of propofol on the auditory steady-state response (ASSR), bispectral (BIS) index, and level of consciousness in two experiments. In Experiment 1, propofol was infused in 11 subjects to obtain effect-site concentrations of 1, 2, 3, and 4 &mgr;g/mL. The ASSR and BIS index were recorded during baseline and at each concentration. The ASSR was evoked by monaural stimuli. Propofol caused a concentration-dependent decrease of the ASSR and BIS index values (r2 = 0.76 and 0.93, respectively;P < 0.0001). The prediction probability for loss of consciousness was 0.89, 0.96, and 0.94 for ASSR, BIS, and arterial blood concentration of propofol, respectively. In Experiment 2, we compared the effects of binaural versus monaural stimulus delivery on the ASSR in six subjects during awake baseline and propofol-induced unconsciousness. During baseline, the ASSR amplitude with binaural stimulation (0.47 ± 0.13 &mgr;V, mean ± sd) was significantly (P < 0.002) larger than with monaural stimulation (0.35 ± 0.11 &mgr;V). During unconsciousness, the amplitude was 0.09 ± 0.09 &mgr;V with monaural and 0.06 ± 0.04 &mgr;V with binaural stimulation (NS). The prediction probability for loss of consciousness was 0.97 (0.04 se) for monaural and 1.00 (0.00 se) for binaural delivery. We conclude that the ASSR and BIS index are attenuated in a concentration-dependent manner by propofol and provide a useful measure of its sedative and hypnotic effect. BIS was easier to use and slightly more sensitive. The ASSR should be recorded with binaural stimulation. The ASSR and BIS index are both useful for assessing the level of consciousness during sedation and hypnosis with propofol. However, the BIS index was simpler to use and provided a more sensitive measure of sedation. Implications We have compared two methods for predicting whether the amount of propofol given to a human subject is sufficient to cause unconsciousness, defined as failure to respond to a simple verbal command. The two methods studied are the auditory steady-state response, which measures the electrical response of the brain to sound, and the bispectral index, which is a number derived from the electroencephalogram. The results showed that both methods are very good predictors of the level of consciousness; however, bispectral was easier to use.

Postdural puncture headache after spinal anaesthesia in young orthopaedic outpatients using 27-g needles.

PurposeTwo large studies reported a very low rate (0.5–1.8%) of postdural puncture headache (PDPH) with the use of 27-G spinal needles. We suspected that it might be higher in young ambulatory patients. The purpose of this study was to establish the rate prospectively in such a patient population using two types of needles.MethodsTwo hundred male and female, outpatients, 18–45 yr, undergoing knee arthroscopy under spinal anaesthesia were randomly assigned to receive spinal anaesthesia with hyperbaric lidocaine 5% using either a Quincke or a Whitacre 27-G needle. Twenty patients choosing general anaesthesia formed a comparative group. Using a previously validated questionnaire, the incidence and nature of PDPH were evaluated by telephone three to five days after surgery by an anaesthetist unaware of the anaesthetic technique used. Once all data were collected, an anaesthetist not involved in the study determined in a blinded fashion which headaches were likely to be PDPH. Grading and classification of headaches were based on several criteria: postural nature, duration, intensity and confinement to bed.ResultsThe overall incidence of PDPH in both spinal groups was 9.3%. The incidence in women, 20.4%, was higherthan in men, 5.5%, (P < 0.05). Only one patient required a blood patch. Both types of needle were comparable with respect to the incidence, severity and duration of PDPH, number of dural punctures and failed spinal blocks.ConclusionThe rate of PDPH was higher than in large published studies with 27-G Quincke and Whitacre needles and greater in women than in men.RésuméObjectifDeux grandes séries ont montré un taux très bas (0,5 –1,8 %) de céphalée post ponction durale (CPPD) avec l’emploi d’aiguilles de calibre 27. Nous avons émis l’hypothèse qu’il pourrait être plus élevé chez de jeunes patients ambulatoires. L’objectif de notre étude était donc d’établir de façon prospective le taux de CPPD chez une telle population de patients en utilisant deux types d’aiguilles.MéthodeDeux cents hommes et femmes, patients ambulatoires de 18 à 45 ans, devant subir une arthroscopie du genou sous rachianesthésie, ont été répartis au hasard pour recevoir une rachianesthésie avec de la lidocaïne hyperbare 5 % à l’aide d’une aiguille 27 Quincke ou Whitcare. Vingt patients, ayant choisi une anesthésie générale, ont formé un groupe témoin. Utilisant un questionnaire validé dans le passé, l’incidence et la nature des CPPD ont été évaluées par téléphone trois à cinq jours après la chirurgie par un anesthésiste qui ne connaissait pas la technique anesthésique employée. Une fois que toutes les données ont été recueillies, un anesthésiste non impliqué dans l’étude a déterminé d’une manière impartiale quelles étaient les céphalées qu’on pouvait étiqueter comme des CPPD. La cotation et la classification des céphalées ont été basées sur quelques critères : la nature posturale, la durée, l’intensité et le confinement au lit.RésultatsL’incidence globale de CPPD des deux groupes sous rachianesthésie a été de 9,3 %. L’incidence chez les femmes, 20,4 %, a été plus élevée que chez les hommes, 5,5 %. (P < 0,05). Un seul patient a requis un hémopatch. Les deux types d’aiguilles ont été jugés semblables en ce qui a trait à l’incidence, la sévérité et la durée des CPPD, au nombre de ponctions durales et de blocages rachidiens non réussis.ConclusionLe taux de CPPD a été plus élevé que lors d’une grande série publiée déjà où l’expérience avait été faite avec des aiguilles 27 Quincke et Whitacre, et plus élevé chez les femmes que chez les hommes.

Adding a selective obturator nerve block to the parasacral sciatic nerve block: an evaluation.

Our aim was to objectively evaluate the efficacy of obturator nerve anesthesia after a parasacral block. Patients scheduled for knee surgery had a baseline adductor strength evaluation. After a parasacral block with 30 mL 0.75% ropivacaine, sensory deficit in the sciatic distribution (temperature discrimination) and adductor strength were assessed at 5-min intervals. Patients with an incomplete sensory block (defined as a temperature discrimination score of less than 2 in the 3 cutaneous distributions of the sciatic nerve tested) 30 min after the parasacral block were excluded from the study. Subsequently, a selective obturator block was performed with 7 mL 0.75% ropivacaine and adductor strength was reassessed at 5 min intervals for 15 min. Finally, a femoral block was performed using 10 mL 0.75% ropivacaine. Patient discomfort level during each block was assessed using a visual analog scale (VAS). Thirty-one patients completed the study. Five patients were excluded as a result of inadequate sensory block in the sciatic distribution 30 min after the parasacral block (success rate of 89%). Thirty min after the parasacral block, adductor strength decreased by 11.3% ± 7% compared with baseline (85 ± 24 versus 97 ± 28 mm Hg, P = 0.002). Fifteen min after the obturator nerve block, adductor muscle strength decreased by an additional 69% ± 7% (16.6 ± 15 versus 85 ± 24 mm Hg, P < 0.0001). VAS scores were similar for all blocks (26 ± 19, 28 ± 24, and 27 ± 19 mm for parasacral, obturator, and femoral respectively). Four parasacral blocks were simulated in 2 fresh cadavers using 30 mL of colored latex solution. The spread of the die in relation to the obturator nerve was assessed. Injection of 30 mL colored latex into cadavers resulted in spread of the injectate restricted to the sacral plexus. These findings demonstrate the unreliability of parasacral block to achieve anesthesia of the obturator nerve. A selective obturator block should be considered in the clinical setting when this is desirable.

Hypobaric spinal anesthesia with ropivacaine plus sufentanil for traumatic femoral neck surgery in the elderly: a dose-response study.

BACKGROUND:In this randomized, prospective trial, we sought to determine the effective dose of hypobaric ropivacaine with sufentanil providing 95% success (ED95) in spinal anesthesia for traumatic femoral neck surgery in the elderly. METHODS:Sixty-eight elderly patients with unilateral hip fracture randomly received 6, 8, 10, or 12 mg spinal hypobaric ropivacaine combined with 5 µg sufentanil. Patients remained in a lateral position for 15 minutes after spinal injection. The dose was considered successful if a unilateral sensory block >T12 was achieved, and there was no need for additional analgesia or conversion to general anesthesia. The ED95 was determined using logit analysis. The incidence of severe and very severe hypotension (systolic blood pressure decrease by >30% and >40% baseline, respectively) and the use of remifentanil were compared among groups using &khgr;2 test for trend. RESULTS:Three patients were excluded because of failure to reach the subarachnoid space. No differences in baseline demographic data were observed among groups. The ED95 for hypobaric ropivacaine was determined to be 9 mg (95% confidence interval, 8–14). Increasing doses of ropivacaine (6, 8, 10, and 12 mg) demonstrated a positive trend with respect to incidence of hypotension (53%, 47%, 87%, and 81%, P = 0.0004) and a negative trend with respect to the use of remifentanil (41%, 12%, 0%, and 0%, P = 0.0004). A significant difference in the level of sensory block (P < 0.0001) was observed among operative and nonoperative sides but not among ropivacaine dosing groups (P = 0.16). No difference in motor blockade, incidence of very severe hypotension, total dose of ephedrine, duration of surgery, patient satisfaction, operating conditions, or surgeon satisfaction scores was observed among groups. No cases of bradycardia were observed. No patient had a preoperative sensory level <T12 after 15 minutes in the lateral decubitus position, and no cases were converted to general anesthesia. There was no difference in undesirable outcomes or postoperative troponin values among groups. CONCLUSIONS:The effective dose of hypobaric ropivacaine combined with sufentanil 5 µg providing 95% success in spinal anesthesia for traumatic femoral neck surgery in the elderly is ED95 = 9 mg (95% confidence interval, 8–14). Using doses exceeding the ED95 may increase the incidence of hypotension. If doses less than the ED95 are chosen, the use of additional analgesia may be necessary.

Postdural Puncture Headache After Spinal Anaesthesia in Young Orthopaedic Outpatients Using 27-G Needles

PURPOSE Two large studies reported a very low rate (0.5-1.8%) of postdural puncture headache (PDPH) with the use of 27-G spinal needles. We suspected that it might be higher in young ambulatory patients. The purpose of this study was to establish the rate prospectively in such a patient population using two types of needles. METHODS Two hundred male and female, outpatients, 18-45 yr, undergoing knee arthroscopy under spinal anaesthesia were randomly assigned to receive spinal anaesthesia with hyperbaric lidocaine 5% using either a Quincke or a Whitacre 27-G needle. Twenty patients choosing general anaesthesia formed a comparative group. Using a previously validated questionnaire, the incidence and nature of PDPH were evaluated by telephone three to five days after surgery by an anaesthetist unaware of the anaesthetic technique used. Once all data were collected, an anaesthetist not involved in the study determined in a blinded fashion which headaches were likely to be PDPH. Grading and classification of headaches were based on several criteria: postural nature, duration, intensity and confinement to bed. RESULTS The overall incidence of PDPH in both spinal groups was 9.3%. The incidence in women, 20.4%, was higher than in men, 5.5%, (P < 0.05). Only one patient required a blood patch. Both types of needle were comparable with respect to the incidence, severity and duration of PDPH, number of dural punctures and failed spinal blocks. CONCLUSION The rate of PDPH was higher than in large published studies with 27-G Quincke and Whitacre needles and greater in women than in men.