Kathryn K. Lauer

A randomized, double-blind comparison of the NK1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting

BACKGROUND: Antiemetics currently in use are not totally effective. Neurokinin-1 receptor antagonists are a new class of antiemetic that have shown promise for chemotherapy-induced nausea and vomiting. This is the first study evaluating the efficacy and tolerability of the neurokinin-1 receptor antagonist, aprepitant, for the prevention of postoperative nausea and vomiting. METHODS: In this multicenter, double-blind trial, we randomly assigned 805 patients receiving general anesthesia for open abdominal surgery to a preoperative dose of aprepitant 40 mg orally, aprepitant 125 mg orally, or ondansetron 4 mg IV. Vomiting, nausea, and use of rescue therapy were assessed over 48 h after surgery. Treatments were compared using logistic regression. RESULTS: Incidence rates for the primary end point (complete response [no vomiting and no use of rescue] over 0–24 h after surgery, tested for superiority of aprepitant) were not different across groups (45% with aprepitant 40 mg, 43% with aprepitant 125 mg, and 42% with ondansetron). The incidence of no vomiting (0–24 h) was higher with aprepitant 40 mg (90%) and aprepitant 125 mg (95%) versus ondansetron (74%) (P < 0.001 for both comparisons), although between-treatment use of rescue and nausea control was not different. Both aprepitant doses also had higher incidences of no vomiting over 0–48 h (P < 0.001). No statistically significant differences were seen among the side effect profiles of the treatments. CONCLUSIONS: Aprepitant was superior to ondansetron for prevention of vomiting in the first 24 and 48 h, but no significant differences were observed between aprepitant and ondansetron for nausea control, use of rescue, or complete response.

Differential effects of deep sedation with propofol on the specific and nonspecific thalamocortical systems: a functional magnetic resonance imaging study.

Background:The current state of knowledge suggests that disruption of neuronal information integration may be a common mechanism of anesthetic-induced unconsciousness. A neural system critical for information integration is the thalamocortical system whose specific and nonspecific divisions may play the roles for representing and integrating information, respectively. How anesthetics affect the function of these systems individually is not completely understood. The authors studied the effect of propofol on thalamocortical functional connectivity in the specific and nonspecific systems, using functional magnetic resonance imaging. Methods:Eight healthy volunteers were instructed to listen to and encode 40 English words during wakeful baseline, light sedation, deep sedation, and recovery in the scanner. Functional connectivity was determined as the temporal correlation of blood oxygen level-dependent signals with seed regions defined within the specific and nonspecific thalamic nuclei. Results:Thalamocortical connectivity at baseline was dominantly medial and bilateral frontal and temporal for the specific system, and medial frontal and medial parietal for the nonspecific system. During deep sedation, propofol reduced functional connectivity by 43% (specific) and 79% (nonspecific), a significantly greater reduction in the nonspecific than in the specific system and in the left hemisphere than in the right. Upon regaining consciousness, functional connectivity increased by 58% (specific) and 123% (nonspecific) during recovery, exceeding their values at baseline. Conclusions:Propofol conferred differential changes in functional connectivity of the specific and nonspecific thalamocortical systems, particularly in left hemisphere, consistent with the verbal nature of stimuli and task. The changes in nonspecific thalamocortical connectivity may correlate with the loss and return of consciousness.

Propofol disrupts functional interactions between sensory and high-order processing of auditory verbal memory

Current theories suggest that disrupting cortical information integration may account for the mechanism of general anesthesia in suppressing consciousness. Human cognitive operations take place in hierarchically structured neural organizations in the brain. The process of low‐order neural representation of sensory stimuli becoming integrated in high‐order cortices is also known as cognitive binding. Combining neuroimaging, cognitive neuroscience, and anesthetic manipulation, we examined how cognitive networks involved in auditory verbal memory are maintained in wakefulness, disrupted in propofol‐induced deep sedation, and re‐established in recovery. Inspired by the notion of cognitive binding, an functional magnetic resonance imaging‐guided connectivity analysis was utilized to assess the integrity of functional interactions within and between different levels of the task‐defined brain regions. Task‐related responses persisted in the primary auditory cortex (PAC), but vanished in the inferior frontal gyrus (IFG) and premotor areas in deep sedation. For connectivity analysis, seed regions representing sensory and high‐order processing of the memory task were identified in the PAC and IFG. Propofol disrupted connections from the PAC seed to the frontal regions and thalamus, but not the connections from the IFG seed to a set of widely distributed brain regions in the temporal, frontal, and parietal lobes (with exception of the PAC). These later regions have been implicated in mediating verbal comprehension and memory. These results suggest that propofol disrupts cognition by blocking the projection of sensory information to high‐order processing networks and thus preventing information integration. Such findings contribute to our understanding of anesthetic mechanisms as related to information and integration in the brain. Hum Brain Mapp33:2487–2498, 2012.

Opioid sedation does not alter intracranial pressure in head injured patients

PurposeThis study aimed to examine the effects of sedative doses of morphine, fentanyl and sufentanil on intracranial pressure (ICP) in head-injured patients in whom changes in mean artenal pressure (MAP) were minimized.MethodsFifteen severely head-injured patients (G5C of ≤8) were randomly assigned to receive either fentanyl. sufentanil or morphine, titrating the drug to a maximal 10% decrease in MAP. The patients were subsequently given an infusion of the same opioid. For four hours, ICP MAP and heart rate were recorded. Results: In all groups, there were no increases in ICP. There was a decrease in MAP in the sufentanil group at 10 min (P < 0.05) and 45 min after the initial opioid bolus. These decreases in MAP were not associated with increases in ICP.ConclusionThe study suggests that when opioids are titrated in head-injured patients, worsening intracranial pressure can be avoided.RésuméObjectifÉtudier les effets de doses sédatives de morphine, de fentanyl et de sufentanil sur la pression intracrânienne (PIC) chez des traumatisés du crâne dont la pression artérielle moyenne (RAM) n’avait que légèrement varié.MéthodesQuinze graves traumatisés du crâne (Échelle de Glasgow ≤ 8) ont été assignés aléatoirement pour recevoir du fentanyl, du sufentanil, ou de la morphine titrés de façon à abaisser la PAM de 10% ou moins. Les patients ont par la suite reçu une perfusion du même morphinique. Pendant quatre heures, la PIC, la PAM et la fréquence cardiaque étaient enregistrées.ResultatsLa PIC est demeurée inchangée dans tous les groupes. La PAM a baissé dans le groupe sufentanil à la 10e minute (P > 0,05) et a la 45e minute qui ont suivi l’administration du bolus initial. Ces diminutions de la PAM n’étaient pas associées à une augmentation de la PIC.ConclusionCette étude suggère que l’administration titrée de morphiniques à des traumatisés du crâne ne provoque pas de détérioration de la pression intracrânienne.

Epidural blood patch as treatment for a surgical durocutaneous fistula

We describe the first case report of an epidural autologous blood patch used for the treatment of a durocutaneous fistula caused by a surgical dural tear. The epidural blood patch cured the patients headache and was followed by a sequelae of back pain that responded to conservative therapy.

Focal cerebral ischemia in rats produced by intracarotid embolization with viscous silicone.

Abstract Many factors contribute to the severity of neuronal cell death and the functional outcome in stroke. We describe an embolic model of focal cerebral ischemia in the rat that does not require craniotomy and is compatible with continuous measurement of regional CBF using multichannel laser Doppler flow (LDF) technique. Either a 22 µ l (large lesion) or 11 µ l (small lesion) bolus of viscous silicone was injected cephalad into the internal carotid artery. Upon injection, LDF decreased abruptly, most severely in the parietal cortex (- 74% ± 5%) in the large lesion and in the occipital cortex (- 69% ± 10%) in the small lesion model. Over the first hour, post-embolization LDF improved in most areas (e.g. - 48% ± 9% parietal, large lesion) but declined in the small lesion group in the occipital region (- 81% ± 8%). CBF measured by [C]14-IAP autoradiography 1 h post-embolization in the large lesion model demonstrated near-hemispheric ischemia (70% of hemisphere) with sparing of cingulate cortex. Autoradiography demonstrated that ischemia in the small lesion was largely cortical. Light microscopy of brains embolized with 11 µ l of dyed silicone showed filling of pial vessels with no silicone in the Circle of Willis or parenchyma. No animals in the large lesion group survived 24 h. Thirteen of 15 animals in the small lesion group survived for two weeks with resolution of initial hemiplegia, ocular asymmetry and weight loss. Hematoxylin-eosin staining two weeks post-embolization showed signs of severe hypoxia and infarction. In conclusion, the intracarotid silicone embolization technique produces a titrable, reproducible permanent ischemic injury by blocking perfusion in the pial circulation, and is amenable to multisite monitoring with laser Doppler flowmetry. The smaller embolus produces cortical infarction with high rate of survival and neurological recovery. [Neurol Res 2002; 24: 181-190]

Neuroanesthesiology fellowship training: Curricular guidelines from the society for neuroscience in anesthesiology and critical care

Standardization and accreditation of fellowship training have been considered in the field of neuroanesthesiology. A prior survey of members of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) suggested strong support for accreditation and standardization. In response, SNACC created a Task Force that developed curricular guidelines for neuroanesthesiology fellowship training programs. These guidelines represent a first step toward standards for neuroanesthesiology training and will be useful if accreditation is pursued in the future.

Peripheral blood pressure changes induced by dobutamine do not alter BOLD signals in the human brain.

In extending the use of functional MRI to neuropharmacology, a primary area of concern is that peripheral blood pressure changes induced by pharmacological agents could independently produce a change in the blood oxygenation level-dependent (BOLD) signal, resulting in difficulties distinguishing or interpreting drug-induced neural activations. In the present study, we utilized intravenous dobutamine, a beta-adrenergic receptor agonist, to increase the mean arterial blood pressure (MABP), while examining the effects of MABP changes on the BOLD signal in cocaine-dependent participants. Dobutamine infusion significantly increased the MABP from 93 +/- 8 mm Hg to 106 +/- 12 mm Hg (P < 0.0005), but did not produce a significant global BOLD signal. Yet, a few voxels in the anterior cingulate showed BOLD signal changes that paralleled the changes in blood pressure (BP). Our observations support the conclusion that following the infusion of psychoactive agents, brain BOLD signals accurately reflect neuronal activity, even in the face of relatively large peripheral cardiovascular effects that transiently increase systemic BP.

Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness

ABSTRACT Recent studies indicate that spontaneous low‐frequency fluctuations (LFFs) of resting‐state functional magnetic resonance imaging (rs‐fMRI) blood oxygen level‐dependent (BOLD) signals are driven by the slow (<0.1 Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic‐induced alteration of consciousness is not well understood. Using rs‐fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory‐motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia.

The effect of midazolam on median nerve somatosensory evoked potentials.

Objective. To quantify the effect of an induction dose of midazolam on median nerve somatosensory evoked potentials.Methods. We studied 10 patients undergoing lumbar spine surgery. After an induction dose of intravenous midazolam was given, MNEPs were collected for ten minutes. After ten minutes the patients were intubated and their anesthetic was supplemented with 0.5% isoflurane, narcotic, and N2O.Results. We found a clinically significant decrease in amplitude and an insignificant delay in latency.Conclusion. When midazolam is used as an anesthetic induction agent, a decrease in amplitude can be expected.ResumeObjectif. Quantification des effets d’une doses d’induction de midazolam sur les potentiels evoques somatosensitifs du nerf médian (PESNM).Méthodes. Nous avons etudies 10 malades operes de l’épine dorsale lombaire. Aprés une induction intraveineuse au midazolam, les PESNM furent recueillis pour 10 minutes. Par apres, les malades regurent une intubation tracheale et leur anesthesic fut supplee à Paide de 0.5% d’isoflurane, de narcotiques et de protoxide d’azote.Resultats. Nous avons trouvé une diminution cliniquement significative de l’amplitude et une prolongation insignifiante de la latence des PESNM.Conclusion. Lors de l’emploi du midazolam comme agent d’induction, Ton peut s’attendre à une réduction de l’amplitude des PESNM.AbstraktZiel. Quantifizierung des Effektes einer Midazolam-Induktionsdosis auf die somatosensorisch evozierten Potentiale des N. medianus.Methoden. Wir untersuchten 10 Patienten, die sich einer Operation im lumbalen Wirbelsäulenbereich unterzogen. Nach einer Induktionsdosis Midazolam i.v. wurden SSEP vom N. medianus fur 10 min gesammelt. Nach 10 min wurden die Patienten intubiert, und die Narkose wurde supplementiert mit 0.5 Vol% Isoflurane, Narkotika und N20.Ergebnisse. Wir fanden eine klinisch signifikante Abnahme der Amplitude und eine nicht signifikante Verlängerung der Latenzzeit.Folgerung. Wenn Midazolam als Einleitungsanästhetikum benutzt wird, kann eine Abnahme der Amplitude erwartet werden.ResumenObjetivo. Cuantificar el efecto de una dosis de induccion de midazolam sobre los potenciales somatosensoriales evocados del nervio mediano (PENV).Metodos. Estudi amos 10 pacientes sometidos a cirugia sobre la columna lumbar. Una vez administrada una dosis de induccion de midazolam intravenoso, se coleccionaron PENV durante diez minutos. Transcurridos los diez minutos los pacientes fueron intubados y su anestesia fue suplementada con 0.5% de isofluorano, narcótico y N20.Resultados. Encontramos una disminucion significativa de la amplitud y un retardo no significativo de la latencia.Conclusión. Cuando se usa midazolam como agente de induccion, debe esperarse una disminución de la amplitud de PENV.