Marc J. Bloom

The Effect of Dexmedetomidine on Perioperative Hemodynamics in Patients Undergoing Craniotomy

BACKGROUND: The perioperative course of patients undergoing intracranial surgery is frequently complicated by hypertensive episodes. Dexmedetomidine (DEX), an &agr;-2 adrenoreceptor agonist, is gaining popularity in neuroanesthesia, because its sympatholytic and antinociceptive properties may improve hemodynamic stability at critical moments of surgery. We designed this study to assess the efficacy of DEX in controlling hypertensive responses in patients undergoing intracranial surgery. METHODS: Patients scheduled for elective craniotomy were randomly assigned to receive either sevoflurane–opioid or sevoflurane–opioid–DEX anesthesia. Bispectral index was used to maintain a similar level of hypnosis in both groups (40–50). Opioids, sevoflurane, and vasoactive medications were titrated in a routine manner, at the discretion of the blinded anesthesiologist managing the case, to maintain systolic blood pressure (SBP) targeted within 90–130 mm Hg and heart rate (HR) between 50 and 90 bpm. Hemodynamic variables were continuously recorded and stored on a computer for analysis. Efficacy of the anesthetic technique in controlling SBP or HR is inversely proportional to the area under the curve (AUC) outside the targeted range. Areas under the curves above and below targeted ranges for SBP-time (AUCsbp mm Hg * min/h) and HR-time (bpm * min/h) were compared. Coefficient of variation was used to assess hemodynamic stability. RESULTS: Seventy-two patients were recruited for the study. Computerized records of 56 patients only were analyzed because of technical problems with data collection in 14 cases. AUCsbp for above the targeted range was significantly lower for patients in the DEX group (P = 0.044). The coefficient of variation for SBP or HR did not differ between groups. A significantly smaller proportion of patients in the DEX group required treatment with antihypertensive medications (12 of 28, 42% vs 24 of 28, 86%, P = 0.0008). The DEX group required fewer opioids in the intraoperative period, but there were no differences in the use of sevoflurane. In the postanesthesia care unit, patients in the DEX group had fewer hypertensive episodes (1.25 ± 1.55 vs 2.50 ± 2.00, P = 0.0114) and were discharged earlier (91 ± 17 vs 130 ± 27 min, P < 0.0001). There were no differences in the requirement for postoperative opioids or antiemetics. CONCLUSIONS: By using indices, which assess a global hemodynamic stability of the anesthetic, we determined that intraoperative DEX infusion was effective for blunting the increases in SBP perioperatively. The use of DEX did not increase the incidence of hypotension or bradycardia, common side effects of the drug.

Design of a laboratory for multineuron studies

The authors describe a number of procedures necessary for the conduct of a multineuron experiment. They have identified three problem areas that are expected to be particularly noticeable as larger assemblies are studied for long periods under conditions where the subject brain is engaged in a behavioral or learning task. The first concerns monitoring a moving animal. It is necessary to develop better multielectrode systems as well as appropriate manipulators for the high degree of stability that is required. Multichannel amplification (perhaps multiplexing with telemetry) must be developed in sizes that can be carried on the head. Second, meaningful feedback must be given to the experiments in time to help modify the conditions of the experiment. Full cross correlation analysis of simultaneously recorded neurons takes a large amount of capacity and time, which slows experimentation. New reduction or abstraction measurement that is practical for rapid feedback is needed. Finally, a better description of a neuronal assembly is needed. A series of new tools deployed to carry out multineuron experiments are described, including electrodes and computer analysis techniques.

On the use of multivariable piecewise-linear models for predicting human response to anesthesia

The standard modeling paradigm used to describe the relationship between input anesthetic agents and output patient endpoint variables are single-input single-output pharmacokinetic-pharmacodynamic (PK-PD) compartment models. We propose the use of multivariable piecewise-linear models to describe the relations between inputs that include anesthesia, surgical stimuli and disturbances to a variety of patient output variables. Subspace identification methods are applied to clinical data to construct the models. A comparison of predicted and measured responses is completed, which includes predictions from PK-PD models, and piecewise-linear time-invariant models.

Localized hypothermia influences assessment of recovery from vecuronium neuromuscular blockade

The purpose of this study was to determine the extent to which localized hypothermia of a monitored extremity alters the assessment of recovery from vecuronium- induced neuromuscular blockade. Bilateral integrated evoked electromyographic (IEMG) responses were measured in the ulnar distribution of 14 anaesthetized patients who had differing upper extremity temperatures as measured at the adductor pollicis to determine whether localized hypothermia alters the clinical assessment of spontaneous recovery from vecuronium- induced neuromuscular blockade. All patients received general anaesthesia with thiopentone, N2O/ O2 and opioid; 11/14 patients received isoflurane for blood pressure control. Bilateral adductor pollicis, oesophageal and ambient temperatures, and IEMG evoked response (t1) expressed as percent unparalyzed control were recorded during the anaesthetic. The difference in evoked response between the warmer and the colder upper extremity was calculated at 25%, 50% and 75% spontaneous recovery from neuromuscular blockade in the warm extremity. Differences in temperature between extremities ranged from 0.2–11° C. The difference in IEMG- evoked response between extremities was proportional to the difference in temperature, and there was a direct correlation (r = 0.78) between IEMG response and extremity temperature; IEMG response was absent when extremity temperature was less than 25° C. We concluded that localized hypothermia in the monitored extremity decreases the IEMG- evoked response to vecuronium neuromuscular blockade; the greater the temperature decrease, the less the evoked response. Thus, the administration of nondepolarizing relaxants may be inappropriately influenced by monitoring neuromuscular blockade in a cold extremity, especially if its temperature is <25° C.RésuméCette étude vise à déterminer jusqu’à quel point l’hypothermie locale mesurée sur une extrémité modifie l’évaluation au moniteur de la récupération du bloc neuromusculaire induit par le vécuronium. La réponse électromyographique intégrée (EIMG) bilatérale est mesurée dans la distribution cubitale chez 14 patients anesthésiés qui présentent des températures différentes au membre supérieur mesurées à l’adducteur du pouce pour déterminer si l’hypothermie locale modifie l’évaluation de la récupération spontanée du bloc neuromusculaire produit par le vécuronium. Tous les patients sont anesthésiés au thiopentone, N2O/O2 et morphiniques, 11 patients sur 14 recevant de l’isoflurane pour contrôler la pression artérielle. La température de l’adducteur du pouce mesurée bilatéralement, la température oesophagienne et ambiante, et la réponse évoquée à l’EIMG (t1) exprimée en pourcentage de la température de l’extrémité d’un contrôle non paralysé sont enregistrés pendant l’ansethésie. La différence de réponse évoquée entre l’extrémité chaude et l’extrémité froide est calculée à 25%, 50% et 75% de la récupération spontanée de l’extrémité chaude. La différence entre les extrémités varie entre 0,2 et 11° C. La différence de la réponse évoquée à l’EIMG entre les extrémités est proportionnelle à la différence de température, et on trouve une corrélation directe (r = 0,78) entre la réponse à l’EIMG et la température de l’extrémité; la réponse à l’EIMG est absente quand la température de l’extrémité est inférieure à 25° C. Nous en concluons que l’hypothermie de l’extrémité monitorée diminue la réponse évoquée du bloc neuromusculaire provoqué par le vécuronium; plus la baisse de température est importante, moindre est la réponse évoquée. Ainsi, l’administration de myorelaxants non dépolarisants peut être influencée faussement par le monitorage du bloc neuromusculaire d’une extrémité froide, surtout si la température est plus basse que 25° C.

Multi-Neuron Experiments: Observation of State in Neural Nets

During the last twenty years it has become common in the neurophysiology laboratory to record and study the electrical activity of single neurons, one at a time, and in a wide variety of stimulus and behavioral conditions in many creatures. Using statistical and computer methods (reviewed in the book by GLASER and RUCHKIN [1]), it is possible to associate firing patterns of single neurons with transmission of particular sensory or motor information. A striking discovery of this era has been that neurons with similar stimulus selectivity (preferences or tuning) lie together in spatially restricted clusters which may repeat at approximately regular spatial intervals. The best known examples are the cortical columns first described by MOUNTCASTLE [2] for somatosensory cortex and by HUBEL and WIESEL [3] for visual cortex.

Sudden hypotension with a test dose of chymopapain

Chymopapain (Chymodiactin) injection for the treatment of herniated intervertebral discs has been associated with allergic reactions of varying severity including cardiovascular collapse and death (1). This reaction to chymopapain, a proteolytic component of carica papaya latex, has been well described (2). However, the current commercially available preparation of the drug contains no preservatives and less extraneous protein and thus may be less of a problem with respect to allergic reactions (3) . The allergic reaction after chymopapain appears to be more common in women, in patients with multiple allergies, and in patients with allergies to papaya or papaya derivatives (l), but at present there appears to be no reliable way to predict which patients will develop a reaction to injection of chymopapain. Premedication with high doses of steroids, H1-, and H2-receptor blockers are thought to decrease the incidence and severity of the allergic reactions. The injection of a small volume of chymopapain into the disc as a test dose is thought to help identify patients at risk by producing a definite but attenuated hypotensive response. This case report describes a patient who had a significant hypotensive episode after a test dose of chymopapain. This report is significant for five reasons. The patient had a history of papaya ingestion, although he had never had an allergic reaction to papaya. Severe hypotension occurred despite large doses of steroids as well as HIand H,-blocking agents administered for 48 hr before and shortly before the

Organization and Perturbation of NeuronalAssemblies

The concept of neuronal assembly as the basic building block of brain activity dates back to Sherrington (Creed, 1932) and (1949). Most of our current knowledge about the nervous system is however based on observations of single neurons, one at a time, thus making possible only tenuous inference of what could be termed “pseudo-population” properties (Georgopoulos, 1988, 1989; Lee et al., 1988; Sparks et al., 1990 among many others). Full study of neuronal assemblies and their internal and external interactions and representations requires simultaneous observation of the activity of as many neurons as possible. Technical advances over the last decade are making this increasingly possible, although never easy (reviews in Kruger, 1983; Gerstein et al., 1983, 1989; and more recently McNaughton et al., 1983; Wilson et al., 1993; Nicoleiis et al., 1997). In addition to the several multiple electrode technologies, there has been a continuous stream of developments that allow the separation of different waveforms observed on each electrode (Abeles and Goldstein, 1977; Zardoshti and Wheeler, 1992; Salganicoff et al., 1988; and many others). Each such waveform presumably is the sign of activity of a distinct individual neuron; some of the sorting methods can accommodate the changes of waveform occurring in a rapid burst of firing, or deal with the complex biological noise background of a typical recording (Wilson et al., 1993, Fee et al., 1996).