Maurice Sosnowski

Differential cross-tolerance between intrathecal morphine and sufentanil in the rat.

By means of a subcutaneously implanted osmotic pump, groups of rats received a constant-rate (1 microliter/h), 7-day intrathecal infusion of saline or one of two mu opioid agonists: sufentanil (0.6 nmol/h) or morphine (20 nmol/h). These concentrations of morphine and sufentanil yielded a comparable near maximal hot-plate response latency on day 1 of the infusion. On day 7, the magnitude of tolerance was assessed in each group by establishing intrathecal dose-response curves and ED50 values for sufentanil and morphine given as a bolus injection. Each infused animal was used for a single bolus injection. In all cases, infusion with the opioid resulted in a rightward shift (increase in ED50) for both morphine and sufentanil as compared to saline-infused animals. The magnitude of the shift, however, was different for the two drugs. Thus in morphine-infused rats, the morphine ED50 increased as compared to saline-infused animals by a factor of 44, whereas the sufentanil ED50 shifted by a factor of 10. In sufentanil-infused animals, the respective shifts in the morphine and sufentanil ED50 values were increased by a factor of 9 and 3, respectively. Thus, a significantly greater shift as compared to saline-infused animals was observed in morphine-infused than in sufentanil-infused animals. Conversely, regardless of the opioid to which the animal was exposed, morphine-tested animals showed a greater rightward shift than did sufentanil-tested animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of remifentanil on N-methyl-D-aspartate receptor : An electrophysiologic study in rat spinal cord

Background:Remifentanil hydrochloride contained in Ultiva® (GlaxoSmithKline, Genval, Belgium) has been incriminated in difficult postoperative pain management, promotion of hyperalgesia, and direct N-methyl-d-aspartate (NMDA) receptor activation, but the involved mechanisms have remained unclear. In the current study, the authors investigated the effects of remifentanil hydrochloride, with and without its vehicle, glycine, on the activation of NMDA receptors and the modulation of NMDA-induced current on neurons inside the lamina II from the dorsal horn of rat spinal cord. Methods:To test these effects, whole cell patch clamp recordings were conducted on acute rat lumbar spinal cord slices. Considering that both components of Ultiva® (remifentanil hydrochloride and glycine) could be involved in NMDA receptor activation, experiments were performed first with remifentanil hydrochloride, second with glycine, and third with the two components within Ultiva®. Results:Remifentanil hydrochloride does not induce any current, whereas 3 mm glycine induced a current that was abolished by the specific NMDA glutamate site antagonist d-2-amino-5-phosphonovalerate. Ultiva® (remifentanil hydrochloride with its vehicle, glycine) also evoked an inward current that was abolished by d-2-amino-5-phosphonovalerate and not significantly different from the glycine-induced current. Application of remifentanil hydrochloride potentiated the NMDA-induced inward current, and this potentiation was abolished by the &mgr;-opioid receptor antagonist naloxone. Conclusion:These results show that remifentanil hydrochloride does not directly activate NMDA receptors. The NMDA current recorded after application of Ultiva® is related to the presence of glycine. Induced NMDA current is potentiated by application of remifentanil hydrochloride through a pathway involving the &mgr;-opioid receptor.

Spinal administration of receptor-selective drugs as analgesics: New horizons

The processing at the spinal cord levels of sensory information is subject to modulation by a number of local receptor systems, including opioids: alpha 2 adrenergic; and to a lesser extent serotonin, GABAB, neuropeptide Y, cholinergic, adenosine, and the NMDA-glutamate site. The functional utility of these multiple systems are only partially understood, but it appears that (a) they may act individually to alter different aspects of the nociceptive sensory message (b) they could be used synergistically to reduce the incidence of side effects by reducing the dose of agents required to yield analgesic effects, and (c) they may function variably in animals made tolerant to classes of receptor agonists.

Desflurane consumption during automated closed-circuit delivery is higher than when a conventional anesthesia machine is used with a simple vaporizer-O2-N2O fresh gas flow sequence

BackgroundThe Zeus® (Dräger, Lübeck, Germany), an automated closed-circuit anesthesia machine, uses high fresh gas flows (FGF) to wash-in the circuit and the lungs, and intermittently flushes the system to remove unwanted N2. We hypothesized this could increase desflurane consumption to such an extent that agent consumption might become higher than with a conventional anesthesia machine (Anesthesia Delivery Unit [ADU®], GE, Helsinki, Finland) used with a previously derived desflurane-O2-N2O administration schedule that allows early FGF reduction.MethodsThirty-four ASA PS I or II patients undergoing plastic, urologic, or gynecologic surgery received desflurane in O2/N2O. In the ADU group (n = 24), an initial 3 min high FGF of O2 and N2O (2 and 4 L.min-1, respectively) was used, followed by 0.3 L.min-1 O2 + 0.4 L.min-1 N2O. The desflurane vaporizer setting (FD) was 6.5% for the first 15 min, and 5.5% during the next 25 min. In the Zeus group (n = 10), the Zeus® was used in automated closed circuit anesthesia mode with a selected end-expired (FA) desflurane target of 4.6%, and O2/N2O as the carrier gases with a target inspired O2% of 30%. Desflurane FA and consumption during the first 40 min were compared using repeated measures one-way ANOVA.ResultsAge and weight did not differ between the groups (P > 0.05), but patients in the Zeus group were taller (P = 0.04). In the Zeus group, the desflurane FA was lower during the first 3 min (P < 0.05), identical at 4 min (P > 0.05), and slightly higher after 4 min (P < 0.05). Desflurane consumption was higher in the Zeus group at all times, a difference that persisted after correcting for the small difference in FA between the two groups.ConclusionAgent consumption with an automated closed-circuit anesthesia machine is higher than with a conventional anesthesia machine when the latter is used with a specific vaporizer-FGF sequence. Agent consumption during automated delivery might be further reduced by optimizing the algorithm(s) that manages the initial FGF or by tolerating some N2 in the circuit to minimize the need for intermittent flushing.

Expression of adenosine A 2A receptors in the rat lumbar spinal cord and implications in the modulation of N-methyl-d-aspartate receptor currents.

BACKGROUND:The presence of A2A receptors in the dorsal horn of the spinal cord remains controversial. At this level, activation of N-methyl-d-aspartate (NMDA) receptors induces wind-up, which is clinically expressed as hyperalgesia. Inhibition of NMDA receptor currents after activation of A2A receptors has been shown in rat neostriatal neurons. In this study, we sought to establish the presence of adenosine A2A receptors in the lamina II of the rat lumbar dorsal horn neurons and investigated whether the activation of A2A receptors is able to modulate NMDA receptor currents. METHODS:Experiments were conducted in the rat lumbar spinal cord. The presence of adenosine A2A receptor transcripts inside the lumbar spinal cord is assessed with the reverse transcriptase polymerase chain reaction (RT-PCR) technique. Western blot experiments are performed at the same level. The RT-PCR technique is also performed specifically in the lamina II, and the presence of adenosine A2A receptor transcripts is assessed in neurons from the lamina II with the single-cell RT-PCR technique. The effect of adenosine A2A receptor activation on NMDA receptor currents is studied by the whole-cell configuration of the patch clamp technique. RESULTS:RT-PCR performed on the lumbar spinal cord revealed the presence of adenosine A2A receptor transcripts. Western blot experiments revealed the presence of A2A receptors in the lumbar spinal cord. RT-PCR performed on the substantia gelatinosa also revealed the presence of adenosine A2A receptor transcripts. Finally, single cell RT-PCR revealed the presence of adenosine A2A receptor transcripts in a sample of lamina II neurons. Patch clamp recordings showed an inhibition of NMDA currents during the application of a selective A2A agonist. CONCLUSIONS:These results demonstrate the presence of A2A receptor on neurons from the substantia gelatinosa of the rat lumbar dorsal horn and the inhibition of NMDA-induced currents by the application of a selective A2A receptor agonist. Therefore, A2A receptor ligands could modulate pain processing at the spinal cord level.

The radial nerve should be blocked before the ulnar nerve during a brachial plexus block at the humeral canal.

PurposeThe brachial plexus block through the humeral canal as described by Dupré is indicated in hand and forearm surgery. This block requires a multi-stimulation technique that emphasizes the necessity of a rigorous and safe technique. Nerve injury associated with regional anesthesia can entail significant morbidity for patients. Thus, we investigated the brachial block sequence in terms of unintended nerve stimulation as a surrogate of potential nerve injury.MethodsSixty patients were randomly allocated in two groups of 30. In Group I the radial nerve was blocked before the ulnar nerve. In Group II the ulnar nerve was blocked before the radial nerve. During the radial nerve approach we recorded, if present, an ulnar nerve response. During the ulnar nerve approach we recorded, if present, a radial nerve response.ResultsIn Group I while looking for the radial nerve, in 50% of the cases, an ulnar motor response was recorded. In Group II while looking for the ulnar nerve, a radial motor response was recorded in 10% of the cases.ConclusionOur results indicate that the radial nerve should be blocked before the ulnar nerve when performing a brachial plexus block at the humeral canal.RésuméObjectifLe blocage du plexus brachial au niveau du canal huméral, selon la technique de Dupré, est indiqué pour des opérations à la main et à l’avant-bras. Ce bloc nécessite une multi-stimulation, technique qui doit être faite avec rigueur et en toute sécurité. La lésion d’un nerf associée à l’anesthésie régionale peut donner lieu à une morbidité importante. La séquence du bloc brachial a donc été examinée sous l’angle de la stimulation involontaire d’un nerf, incident porteur d’une lésion potentielle à ce nerf.MéthodeSoixante patients ont été répartis aléatoirement en deux groupes de 30. Dans le groupe I, le nerf radial a été bloqué avant le nerf cubital. Dans le groupe II, nous avons fait l’inverse. Pendant l’approche du nerf radial, nous avons noté la présence ou non d’une réponse du nerf cubital. Pendant l’approche du nerf cubital, nous avons noté la réponse du nerf radial selon le cas.RésultatsDans le groupe I, pendant le blocage du nerf radial, nous avons noté une réponse motrice cubitale dans 50% des cas. Dans le groupe II, pendant le blocage du nerf cubital, nous avons noté une réponse motrice radiale dans 10% des cas.ConclusionNos résultats indiquent que le nerf radial doit être bloqué avant le nerf cubital quand nous réalisons un bloc du plexus brachial au niveau du canal huméral.

Absence of implicit and explicit memory during propofol/remifentanil anaesthesia

Background and objective: High doses of opioid associated with low doses of hypnotic is a popular anaesthetic technique since the use of remifentanil has become widespread. This type of anaesthesia could result in a higher incidence of implicit memory. Methods: Ten patients were anaesthetised with a target‐controlled infusion of remifentanil (target concentration of 8 ng mL−1) combined with a target‐controlled infusion of propofol with progressive stepwise increases until loss of consciousness was reached. A tape containing 20 words was then played to the patients. Bispectral index (BIS, Aspect Medical Systems, Newton, MA, USA) was continuously monitored during the whole study period. Implicit and explicit memories were tested between 2 and 4 h after recovery. Results: Loss of consciousness was obtained with a mean calculated propofol plasma concentration of 1.3 ± 0.4 μg mL−1. At this low hypnotic concentration no implicit or explicit memory was found in the three postoperative memory tests. Median (range) BIS value during word presentation was 93 (80‐98). Conclusions: In our group of young American Society of Anesthesiologists (ASA) I/II patients, no explicit or implicit memory was found when the calculated concentration of propofol combined with a high concentration of remifentanil was maintained at the level associated with loss of consciousness with high BIS values.

Sciatic nerve block in the popliteal fossa: description of a new medial approach

PurposeSciatic nerve blocks through lateral approaches in the popliteal fossa have been proposed. We describe a new medial approach to the sciatic nerve at this level.MethodsAfter an anatomical study on six cadavers, we performed sciatic nerve blocks on 20 patients. A 100-mm insulated needle and a nerve stimulator were used; 20 mL of lidocaine 1.5% with epinephrine were injected.ResultsPatients lied in the supine position, the thigh flexed, abducted and rotated externally (30° in all directions). The leg was flexed at 130°. In this position, above the adductor tubercle, a depression known as Jobert’s fossa is palpated. Through this groove, a medial approach to the sciatic nerve at the level of the popliteal fossa is possible. The mean distance between the adductor tubercle and the puncture site is 6.18 cm (range 4–8 cm) and the mean distance between the skin and the sciatic nerve is 6.62 cm (range 4–9 cm). Mean time to perform the block was 100 sec (range 55–165 sec). Complete motor blockade was obtained after a mean time of 30 min (range 5–60 min) inside the common peroneal nerve area and 43 min (range 15–75 min) inside the tibial nerve area. Motor block was complete in 17 patients and sensory block in 18 patients. No vessel puncture was observed.ConclusionWe describe a new medial approach to the sciatic nerve in the popliteal fossa. More studies will be required to demonstrate the technique is effective and safe.RésuméObjectifDes blocs du nerf sciatique par des approches latérales du creux poplité ont été proposés. Nous décrivons une nouvelle approche médiale du nerfsciatique à ce niveau.MéthodeAprès une étude anatomique sur six cadavres, nous avons réalisé des blocs du nerfsciatique sur 20 patients. Une aiguille isolée de 100 mm et un neurostimulateur ont été utilisés ; 20 mL de lidocaïne à 1,5% avec épinéphrine ont été injectés.RésultatsLes patients étaient étendus décubitus dorsal, la cuisse fléchie, en abduction et en rotation vers l’extérieur (de 30° dans toutes les directions). La jambe était fléchie à 130°. Dans cette position, une dépression connue sous le nom de fosse de Jobert est palpée au-dessus du tubercule de l’adducteur. Par ce sillon, une approche médiale du nerf sciatique est possible au niveau du creux poplité. La distance moyenne entre le tubercule de l’adducteur et le site de ponction est de 6,18 cm (limites 4–8 cm) et la distance moyenne entre la peau et le nerfsciatique est de 6,62 cm (limites 4–9 cm). Le temps moyen nécessaire pour réaliser le bloc a été de 100 sec (limites 55–165 sec). Le blocage moteur complet a été obtenu après un temps moyen de 30 min (limites 5–60 min) dans la zone du nerf sciatique poplité externe et de 43 min (limites 15–75 min) dans la zone du nerf tibial. Le bloc moteur a été complet chez 17 patients et le bloc sensitifchez 18 patients. Aucune ponction vasculaire n’a été observée.ConclusionNous décrivons une nouvelle approche médiale du nerf sciatique dans le creux poplité. Il reste à démontrer l’efficacité et la sécurité de la technique.

The Anesthetic Management of a Case of Tracheal Necrosis

A 63-yr-old female patient developed a tracheal necrosis after esophageal resection with gastric interposition. We report the anesthetic management of this patient undergoing tracheal repair focusing on an original airway management and ventilation strategy.

Potential Benefit of Intra-operative Administration of Ketorolac on Breast Cancer Recurrence According to the Patient’s Body Mass Index

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently used in some countries as analgesics in primary cancer surgery. Retrospective studies suggest that NSAIDs could reduce breast cancer recurrences. Because NSAIDs also act on biological mechanisms present in patients with increased adiposity, we aimed at assessing whether the intra-operative administration of ketorolac or diclofenac would be associated with a reduction of recurrence in patients with elevated body mass index (BMI). Methods We considered two institutional retrospective series of 827 and 1007 patients evaluating the administration of ketorolac (n = 529 with, n = 298 without) or diclofenac (n = 787 with, n = 220 without). The BMI subgroups were defined as less than 25 kg/m2 (lean) and 25 or more kg/m2 (overweight and obese). Cumulative incidence estimation of distant metastases as well as Fine-Gray and Dixon-Simon models was used. These analyses were adjusted for clinico-pathological variables. All statistical tests were two-sided. Results The administration of ketorolac was statistically significantly associated with decreased incidence of distant recurrences (adjusted hazard ratio [aHR]= 0.59, 95% confidence interval [CI] = 0.37 to 0.96, P = .03). In particular, the association was evident in the high-body mass index (BMI) group of patients (aHR = 0.55, 95% CI = 0.31 to 0.96, P = .04). The administration of diclofenac was not statistically significantly associated with decreased incidence of distant recurrences, either in the global population or in the BMI subgroups. Conclusions These results show that the intra-operative administration of ketorolac, but not diclofenac, is statistically significantly associated with a reduction of distant recurrences in patients with increased BMI. Altogether, this study points to a potentially important repositioning of ketorolac in the intra-operative treatment of patients with elevated BMI that, if prospectively validated, might be as impactful as and cheaper than adjuvant systemic anticancer therapies.