Craig R. Ries

Quantifying cortical activity during general anesthesia using wavelet analysis

This paper reports on a novel method for quantifying the cortical activity of a patient during general anesthesia as a surrogate measure of the patients level of consciousness. The proposed technique is based on the analysis of a single-channel (frontal) electroencephalogram (EEG) signal using stationary wavelet transform (SWT). The wavelet coefficients calculated from the EEG are pooled into a statistical representation, which is then compared to two well-defined states: the awake state with normal EEG activity, and the isoelectric state with maximal cortical depression. The resulting index, referred to as the wavelet-based anesthetic value for central nervous system monitoring (WAV/sub CNS/), quantifies the depth of consciousness between these two extremes. To validate the proposed technique, we present a clinical study which explores the advantages of the WAV/sub CNS/ in comparison with the BIS monitor (Aspect Medical Systems, MA), currently a reference in consciousness monitoring. Results show that the WAV/sub CNS/ and BIS are well correlated (r=0.969) during periods of steady-state despite fundamental algorithmic differences. However, in terms of dynamic behavior, the WAV/sub CNS/ offers faster tracking of transitory changes at induction and emergence, with an average lead of 15-30 s. Furthermore, and conversely to the BIS, the WAV/sub CNS/ regains its preinduction baseline value when patients are responding to verbal command after emergence from anesthesia. We conclude that the proposed analysis technique is an attractive alternative to BIS monitoring. In addition, we show that the WAV/sub CNS/ dynamics can be modeled as a linear time invariant transfer function. This index is, therefore, well suited for use as a feedback sensor in advisory systems, closed-loop control schemes, and for the identification of the pharmacodynamic models of anesthetic drugs.

Continuous noninvasive blood pressure measurement by pulse transit time

Blood pressure measurement is performed either invasively by an intra arterial catheter or noninvasively by cuff sphygmomanometry. The invasive method is continuous and accurate but has increased risk; the cuff is safe but less reliable and infrequent. A reliable continuous noninvasive blood pressure measurement is highly desirable. While the possibility of using pulse transit time to monitor blood pressure has previously been investigated, most studies were limited to calculating the correlation of the pulse transit time and blood pressure under rather static conditions. The relationship between the pulse transit time and blood pressure is yet to be clearly identified. This paper focuses on the modeling between the two values and presents results on cases where dramatic variation in blood pressure of the patient was induced by drug administration or surgical stimulation.

A wavelet based de-noising technique for ocular artifact correction of the electroencephalogram

This paper investigates a wavelet based denoising of the electroencephalogram (EEG) signal to correct for the presence of the ocular artifact (OA). The. proposed technique is based on an over-complete wavelet expansion of the EEG as follows: i) a stationary wavelet transform (SWT) is applied to the corrupted EEG; ii) the thresholding of the coefficients in the lower frequency bands is performed; iii) the de-noised signal is reconstructed. This paper demonstrates the potential of the proposed technique for successful OA correction. The advantage over conventional methods is that there is no need for the recording of the electrooculogram (EOG) signal itself. The approach works both for eye blinks and eye movements. Hence, there is no need to discriminate between different artifacts. To allow for a proper comparison, the contaminated EEG signals as well as the corrected signals are presented together with their corresponding power spectra.

Opisthotonos following propofol: A nonepileptic perspective and treatment strategy

In this report of opisthotonos during recovery from propofol anaesthesia, we relate clinical observations with scientific considerations, and propose a strategy for treatment of this rare side effect. Following a brief operative procedure, a healthy 29-yr-old woman developed recurrent opisthotonos while recovering from anaesthesia with alfentanil, propofol, and nitrous oxide. In contrast to accumulating reports, the patient remained conscious during each episode of back extension and retrocollis. The preservation of consciousness and similarities to strychnine-induced opisthotonos suggest to us that the mechanism may have a brainstem and spinal origin. Recent investigations show that propofol potentiates the inhibitory transmitters glycine and γ-aminobutyric acid (GABA) which would enhance spinal inhibition during anaesthesia. Postanaesthetic opisthotonos, however, may be due to a propofol-induced tolerance to inhibitory transmitters. This rebound phenomenon would lead to an acute, enduring refractoriness in inhibitory pathways of the brainstem and spinal cord, resulting in increased activity of extensor motoneurons. We recommend a therapeutic strategy that restores inhibition by glycine and GABA at multiple sites; the preferred therapeutic agents would be diazepam and physostigmine. The episodes are usually short-lived, but two of the reviewed 17 patients developed recurrent retrocollis for four and 23 days following antiepileptic drug therapy. Since high doses of phenytoin and carbamazepine can result in opisthotonos, we recommend that anticonvulsants be reserved for post-anaesthetic patients with electroencephalographic evidence of seizure activity.RésuméDans ce rapport d’opisthotonos survenant au cours du réveil d’une anesthésie réalisée au propofol, nous décrivons les observations cliniques avec leurs considérations scientifiques, et proposons une stratégie de traitement de cet effet inusité. Après une chirurgie brève, une patiente de 29 ans, en bonne santé, développe un opisthonos récurrent alors qu’elle se réveille d’une anesthésie réalisée avec alfentanil, propofol et protoxyde d’azote. Contrairement aux observations accumulées, elle reste consciente à chaque épisode d’extension dorsale et cervicale. La persistence de la conscience ainsi que la similitude de cet opisthonos avec celui induit par la strychnine nous suggère que le mécanisme peut avoir son origine du tronc cérébral et de la moelle. Des investigations récentes montrent que le propofol potentialise la glycine et l’acide γ-aminobutyrique (GABA), neurotransmetteurs inhibiteurs, ce qui pourrait accentuer l’inhibition médullaire pendant l’anesthésie. L’opisthonos postanesthésique peut être secondaire à une tolérance aux transmetteurs inhibiteurs induite par le propofol. Ces phénomènes de rebond pourraient conduire à une résistance aiguë et durable aux influx inhibiteurs du tronc cérébral et de la moelle, résultant en une activité accrue des motoneurones extenseurs. Nous recommandons une stratégie thérapeutique qui restaure l’inhibition de la glycine et du GABA à des sites multiples: les agents thérapeutiques de choix seraient le diazepam et la physostigmine. Les épisodes sont habituellement brefs, mais deux des 17 patients revus ont développé une extension du cou récurrente à quatre et 23 jours après un traitement antiépileptique. Puisque des doses élevées et phénytoïne et de carbamazépine peuvent entraîner un opisthonos, nous recommandons que les anticonvulsivants soient réservés aux patients qui présentent une activité comitiale à l’élearoencéphalogramme après leur anesthésie.

Midazolam premedication delays recovery after propofol without modifying involuntary movements

Midazolam has GABAergic effects in children that may modify propofol-induced involuntary movements, yet delay recovery. In a double-blind, randomized study, 24 children (2-7 yr of age, ASA physical status I or II) undergoing short surgical procedures received midazolam 0.5 mg/kg (Group M) or placebo (Group P) per os 20-30 min before propofol anesthesia (5 mg/kg intravenously followed by an infusion). Blind observers scored sedation and anxiety levels (scale 1-4) before premedication, at separation from parents, and at induction of anesthesia. Induction and emergence were videotaped, and body movements were recorded. During recovery, times to eye opening and maximum Steward (SS = 6) and Vancouver Sedative Recovery (VSRS = 22) scores were noted. Parents were questioned about side effects that may have occurred during the following week. Both groups were similar in age, sex, weight, timing of premedication, propofol dose, and duration of surgery. The incidence of involuntary movements did not differ between groups but was higher at induction (79%) than on emergence (25%) (P < 0.05). Anxiety and sedation scores were similar in Group P and Group M, but recovery took longer after midazolam, with eye opening (mean +/- SD) 24 +/- 7 vs 43 +/- 18 min, maximum SS (median and range) 27 (13-37) vs 55 (24-138) min, and maximum VSRS 51 (30-100) vs 80 (50-130) min. Children returned to normal activity in 1 (0-5) day, and none exhibited neurological complications. We conclude that an oral premedicant dose of midazolam prolongs recovery from anesthesia in children without affecting dystonic movements after propofol. (Anesth Analg 1997;85:50-4)

Introduction to Automated Drug Delivery in Clinical Anesthesia

Control technology has been applied to a wide variety of industrial and domestic applications to improve performance, safety and efficiency. Anesthesia, a critical aspect of clinical and emergency medicine, has not yet benefited from such technological advances. The lack of dedicated feedback sensors, and the large inter- and intra-patient variability in terms of patients’ response to drug administration, have seriously limited the effectiveness and reliability of closed-loop controllers in clinical settings. However, recent advances in sensing devices, along with robust nonlinear control theories, have generated new hopes that the gap between manual and automated control of anesthesia can finally be bridged. This paper addresses the pharmacological principles of clinical anesthesia in a context appropriate for control engineers. Concepts and terminology, monitoring issues, as well as drug dose vs. response relationships, are covered.

Propofol reduces cognitive impairment after electroconvulsive therapy

Background: Cognitive impairments are the main complication after electroconvulsive therapy (ECT). Modification of treatment parameters has been shown to affect the magnitude of these impairments, but the role of anesthetic type remains unclear. This study tested whether there is a difference in cognitive impairments immediately after ECT with propofol compared to thiopental anesthesia. Methods: This randomized, double-blind, crossover study included 15 patients receiving right unilateral ECT for depression. Patients received propofol or thiopental on alternating ECTs up to 6 treatments. Immediate and delayed verbal memory, motor speed, reaction speed, visuospatial, and executive functions were assessed 45 minutes after each ECT. Differences were assessed with repeated measures analysis of variance. Results: Cognitive impairments were reduced after ECT with propofol compared to thiopental. Time to emergence was quicker and EEG seizure duration was shorter after propofol treatments. There was no significant correlation between seizure duration and neuropsychological test performance. Conclusions: Our results indicate that cognitive impairments in the early recovery period after ECT are reduced with propofol compared to thiopental anesthesia. We suggest that, in addition to ECT parameters, the type of anesthetic agent should be considered to reduce cognitive impairments after ECT.

QX-314 Produces Long-lasting Local Anesthesia Modulated by Transient Receptor Potential Vanilloid Receptors in Mice

Background:The quaternary lidocaine derivative QX-314 is now known to produce long-lasting local anesthesia despite its positive charge. However, recent research suggests that the transient receptor potential vanilloid receptor agonist, capsaicin, should reduce the onset and offset times, whereas the transient receptor potential vanilloid receptor antagonist, capsazepine, should delay the onset time of sensory blockade by QX-314. Methods:Sensory blockade in the tail of the conscious mouse was investigated using QX-314 2.5% in combination with capsaicin 0.1% and/or capsazepine (50 &mgr;g/ml). After tail injection, onset and offset times of local anesthesia were measured using the hot water tail-flick latency test. Results:Capsaicin reduced the onset time of local anesthesia by QX-314 by more than 75% (Mann–Whitney test, P = 0.007; n = 10 per group) with no effect on the offset time of QX-314. For QX-314 without capsaicin, the onset and offset times were 23 min (interquartile range 15–30 min) and 300 min (interquartile range 285–375 min), respectively. For QX-314 with capsaicin, the onset and offset times were 4 min (interquartile range 3–8 min) and 360 min (interquartile range 285–435 min), respectively. In the antagonist study, capsazepine without added capsaicin decreased QX-314’s efficacy, as 6 out of 9 mice did not develop sensory blockade after 90 min (Fisher exact test, P = 0.009). Conclusion:We have confirmed in a sensory blockade model that QX-314 is a local anesthetic with a slow onset and a long duration of reversible blockade. Capsaicin, a transient receptor potential vanilloid receptor agonist, accelerated QX-314’s onset kinetics, whereas capsazepine, a transient receptor potential vanilloid receptor antagonist, decreased QX-314’s efficacy. These observations raise the possibility that endovanilloids may modulate cell entry of QX-314.

Addition of femoral 3-in-1 blockade to intra-articular ropivacaine 0.2% does not reduce analgesic requirements following arthroscopic knee surgery.

PurposeTo test the hypothesis that the addition of a preincisional femoral 3-in-1 block to intra-articular instillation with ropivacaine 0.2% at the end of surgery improves postoperative pain control in patients undergoing arthroscopic anterior cruciate ligament reconstruction (ACLR) under general anesthesia.MethodsIn a prospective, randomized, placebo-controlled, double-blind trial, we studied 44 patients scheduled for inpatient ACLR. Prior to incision, the treatment group (n = 22) received a femoral 3-in-1 block with 40 ml ropivacaine 0.2%, augmented by infiltrations of the lateral and anteromedial incisions with 20 ml ropivacaine 0.2% at the end of the procedure. The control group (n = 22) received saline 0.9% instead of ropivacaine. All patients received an intra-articular instillation with 30 ml ropivacaine 0.2% at the end of surgery. The primary efficacy variable was 24 hr morphine consumption postoperatively standardized by weight, administered intravenously via a patient-controlled analgesia (PCA) pump.ResultsThere was no difference between both groups in 24 hr PCA morphine consumption postoperatively (control, 0.45 ± 0.44 [mean ± SD] mg·kg−1; treatment, 0.37 ± 0.50 mg·kg−1; P = 0.55). No difference was found in postoperative visual analog scale pain scores, adverse events, or vital signs. In the treatment group, R = 10/22 patients did not require postoperative morphine compared with R = 6/22 in the control group (P = 0.35).ConclusionWe found no effect of a femoral 3-in-1 block with ropivacaine 0.2% on postoperative analgesic consumption, compared to intra-articular instillation with ropivacaine 0.2% alone, in patients undergoing ACLR under general anesthesia.RésuméObjectifVérifier l’hypothèse selon laquelle l’addition, avant l’incision, d’un blocage fémoral 3 en I à l’instillation intra- articulaire de ropivacaïne 0,2% de fin d’opération, améliore le soulagement de la douleur postopératoire chez les patients qui subissent une reconstruction arthroscopique du ligament croisé antéro-externe (RLCA) sous anesthésie générale.MéthodeIl s’agit d’un essai prospectif randomisé en double insu contre placebo concernant 44 patients qui subissent une RLCA élective en chirurgie ambulatoire. Avant l’incision, le groupe traité (n = 22) a reçu un bloc fémoral 3 en I de 40 ml de ropivacaïne 0,2%, augmenté par des infiltrations des incisions latérale et antéromédiane de 20 ml de ropivacaine 0,2% à la fin de l’intervention. Le groupe témoin (n = 22) a reçu une solution salée à 0,9%. Tous les patients ont reçu une instillation intra-articulaire de 30 ml de ropivacaine 0,2% à la fin de l’opération. La principale variable d’efficacité a été la demande de morphine postopératoire à 24 h, uniformisée selon le poids, dont l’administration intraveineuse s’est faite à l’aide d’une pompe d’analgésie contrôlée par le patient (ACP).RésultatsLa demande postopératoire de morphine ACP à 24 h n’a pas présenté de différence intergroupe (témoin, 0,45 ± 0,44 [moyenne ± écart type]mg·kg−1; traitement, 0,37 ± 0,50 mg·kg−1; P = 0,55), ni les seuils de douleur postopératoire, selon l’échelle visuelle analogue, les effets secondaires et les signes vitaux. Dans le groupe de traitement, 10/22 patients n’ont pas demandé de morphine postopératoire et 6/22 dans le groupe témoin (P = 0,35).ConclusionNous n’avons pas noté d’effet du blocage fémoral 3 en I de ropivacaïne 0,2% sur la demande postopératoire d’analgésique, comparé à l’instillation intra-articulaire de ropivacaïne 0,2% seule, chez des patients qui subissent une RLCA sous anesthésie générale.

Combined pre- and post-surgical bupivacaine would infiltrations decrease opioid requirements after knee ligament reconstruction

Purpose: To test the efficacy of a combination of selective pre- and post-surgical local anesthetic infiltrations of the knee, compared with standard intra-articular injection at the end of surgery alone, to reduce postoperative opioid requirements following arthroscopic cruciate ligament reconstruction (ACLR).Methods: In a double-blind, randomized, controlled trial, we studied 23 patients (ASA I or II) scheduled for elective ACLR under general anesthesia. The treatment group (n=12) received infiltrations with bupivacaine 0.25% with epinephrine 1:200 000 presurgically (10 ml into the portals, 10 ml at the medial tibial incision site, 10 ml at the lateral femoral incision site, and 10 ml intra-articularly) and postsurgically (5 ml at the medial tibial incision and 10 ml at the lateral femoral incision). The control group (n=11) received infiltrations with saline 0.9% in the same manner. All patients received a standard intra-articular local anesthetic instillation of the knee (25 ml of bupivacaine 0.25% with epinephrine 1:200 000) at the completion of surgery.Results: Postoperative opioid requirements were lower in the treatment group (5.8±2.9 mg morphine equivalent) than in the control group (13.7±5.8 mg;P=0.008). Treatment patients were ready for discharge approximately 30 min earlier than control patients (P=0.046). There were no adverse events in the treatment group. In the control group, 2/11 patients vomited and a third experienced transient postoperative diaphoresis, dizziness and pallor.Conclusion: We conclude that a combination of selective pre- and post-surgical would infiltration with bupivacaine 0.25% provides superior analgesia compared with a standard post-surgical intra-articular injection alone.RésuméObjectif: Tester l’efficacité d’une combinaison d’infiltrations sélectives du genou, préopératoires et postopératoires, avec un a nesthésique local, comparée à l’injection intra-articulaire régulière de fin d’intervention seulement, dans le but de réduire les besoins postopératoires d’opioïdes à la suite de la reconstruction arthroscopique du ligament croisé (RALC).Méthode: L’étude randomisée, contrôlée et à double insu a porté sur 23 patients (ASA I ou II) pour qui une RALC avait été prévue sous anesthésie générale. Les patients étudiés (n=12) ont reçu des infiltrations préchirurgicales de bupivacaïne à 0,25 % avec de l’épinéphrine à 1:200 000 (10 ml via le portail, 10 ml au site d’incision tibial médian, 10 ml dans l’incision fémorale latérale et 10 ml intra-articulaire) et postchirurgicales (5 ml dans l’incision tibiale médiane et 10 ml dans l’incision fémorale latérale). Les patients témoins (n=11) ont reçu des infiltrations de solution salée à 0,9 %, administrées de la même manière. Tous les patients ont reçu une instillation anesthésique standard locale dans l’articulation du genou (25 ml de bupivacaïne à 0,25 % avec de l’épinéphrine à 1:200 000) à la fin de l’opération.Résultats: Les patients testés ont demandé moins d’opioïdes postopératoires (5,8±2,9 mg d’équivalent de morphine) que les patients témoins (13,7±5,8 mg;P=0,008). Ils ont pu recveoir leur congé 30 min plus tôt que les patients témoins (P=0,046). On n’a pas noté d’effets indésirables chez les patients testés. Parmi les patients témoins, 2/11 ont eu des vomissements et un tiers a présenté une diaphorèse postopératoire transitoire, des étourdissements et de la pâleur.Conclusion: Une combinaison d’infiltrations préchirurgicales et postchirurgicales du site d’incision avec de la bupivacaïne à 0,25 % fournit une analgésie supérieure à la seule injection intra-articulaire postchirurgicale standard.