Entropy and bispectral index for assessment of sedation, analgesia and the effects of unpleasant stimuli in critically ill patients: an observational study

INTRODUCTION: Sedative and analgesic drugs are frequently used in critically ill patients. Their overuse may prolong mechanical ventilation and length of stay in the intensive care unit. Guidelines recommend use of sedation protocols that include sedation scores and trials of sedation cessation to minimize drug use. We evaluated processed electroencephalography (response and state entropy and bispectral index) as an adjunct to monitoring effects of commonly used sedative and analgesic drugs and intratracheal suctioning. METHODS: Electrodes for monitoring bispectral index and entropy were placed on the foreheads of 44 critically ill patients requiring mechanical ventilation and who previously had no brain dysfunction. Sedation was targeted individually using the Ramsay Sedation Scale, recorded every 2 hours or more frequently. Use of and indications for sedative and analgesic drugs and intratracheal suctioning were recorded manually and using a camera. At the end of the study, processed electroencephalographical and haemodynamic variables collected before and after each drug application and tracheal suctioning were analyzed. Ramsay score was used for comparison with processed electroencephalography when assessed within 15 minutes of an intervention. RESULTS: The indications for boli of sedative drugs exhibited statistically significant, albeit clinically irrelevant, differences in terms of their association with processed electroencephalographical parameters. Electroencephalographical variables decreased significantly after bolus, but a specific pattern in electroencephalographical variables before drug administration was not identified. The same was true for opiate administration. At both 30 minutes and 2 minutes before intratracheal suctioning, there was no difference in electroencephalographical or clinical signs in patients who had or had not received drugs 10 minutes before suctioning. Among patients who received drugs, electroencephalographical parameters returned to baseline more rapidly. In those cases in which Ramsay score was assessed before the event, processed electroencephalography exhibited high variation. CONCLUSIONS: Unpleasant or painful stimuli and sedative and analgesic drugs are associated with significant changes in processed electroencephalographical parameters. However, clinical indications for drug administration were not reflected by these electroencephalographical parameters, and barely by sedation level before drug administration or tracheal suction. This precludes incorporation of entropy and bispectral index as target variables for sedation and analgesia protocols in critically ill patients.

Multimodal approach in the use of clinical scoring, morphological MRI and biochemical T2-mapping and diffusion-weighted imaging in their ability to assess differences between cartilage repair tissue after microfracture therapy and matrix-associated autologous chondrocyte transplantation: a pilot study

OBJECTIVE: The aim of the present pilot study is to show initial results of a multimodal approach using clinical scoring, morphological magnetic resonance imaging (MRI) and biochemical T2-relaxation and diffusion-weighted imaging (DWI) in their ability to assess differences between cartilage repair tissue after microfracture therapy (MFX) and matrix-associated autologous chondrocyte transplantation (MACT). METHOD: Twenty patients were cross-sectionally evaluated at different post-operative intervals from 12 to 63 months after MFX and 12-59 months after MACT. The two groups were matched by age (MFX: 36.0+/-10.4 years; MACT: 35.1+/-7.7 years) and post-operative interval (MFX: 32.6+/-16.7 months; MACT: 31.7+/-18.3 months). After clinical evaluation using the Lysholm score, 3T-MRI was performed obtaining the MR observation of cartilage repair tissue (MOCART) score as well as T2-mapping and DWI for multi-parametric MRI. Quantitative T2-relaxation was achieved using a multi-echo spin-echo sequence; semi-quantitative diffusion-quotient (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) was prepared by a partially balanced, steady-state gradient-echo pulse sequence. RESULTS: No differences in Lysholm (P=0.420) or MOCART (P=0.209) score were observed between MFX and MACT. T2-mapping showed lower T2 values after MFX compared to MACT (P=0.039). DWI distinguished between healthy cartilage and cartilage repair tissue in both procedures (MFX: P=0.001; MACT: P=0.007). Correlations were found between the Lysholm and the MOCART score (Pearson: 0.484; P=0.031), between the Lysholm score and DWI (Pearson:-0.557; P=0.011) and a trend between the Lysholm score and T2 (Person: 0.304; P=0.193). CONCLUSION: Using T2-mapping and DWI, additional information could be gained compared to clinical scoring or morphological MRI. In combination clinical, MR-morphological and MR-biochemical parameters can be seen as a promising multimodal tool in the follow-up of cartilage repair.

Evaluation of peri-operative epidural analgesia with ropivacaine, ropivacaine and sufentanil, and ropivacaine, sufentanil and epinephrine in isoflurane anesthetized dogs undergoing tibial plateau levelling osteotomy

The purpose of this study was to compare four epidural protocols for peri-operative analgesia in dogs undergoing tibial plateau levelling osteotomy. Forty client-owned dogs were randomly assigned to one of four treatments - groups R0.5 and R1 received 0.5mg/kg and 1mg/kg ropivacaine, respectively. Group SR0.5 received 1mug/kg sufentanil plus 0.5mg/kg ropivacaine, and group SER0.5 received 1mug/kg sufentanil, 0.5mg/kg ropivacaine plus 6mug/kg epinephrine. Dilution, when required, was performed with saline, so that the injected volume was always 0.2mL/kg. Intra-operatively, nociception assessment was based on the evaluation of changes in heart rate, respiratory rate and mean arterial pressure. Post-operative pain assessment was performed using the Glasgow visual analogue pain scale, and an ad hoc multifactorial pain score. Motor block was evaluated using a modified Bromage score. Intra-operatively, none of the animals was hypotensive. All groups except SER0.5 required rescue intra-operative fentanyl (40%, 30% and 40% of the animals in groups R0.5, R1 and SR0.5, respectively). Group SER0.5 showed lower post-operative pain scores, and group R1 significantly greater motor block, compared to the other treatment groups. None of the dogs had urinary retention. Epidural sufentanil-epinephrine-ropivacaine provided superior peri-operative analgesia compared to the other treatments, without producing clinically relevant side effects.

Preemptive carprofen for peri-operative analgesia in dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO): a prospective, randomized, blinded, placebo controlled clinical trial

Eighteen client-owned dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO) were included in this blinded clinical study and randomly assigned to one of two treatment groups. Group C (carprofen) received intravenous (IV) carprofen, 4 mg/kg, prior to anesthesia, whereas group P (placebo) received IV saline. General anesthesia was maintained with isoflurane in oxygen and a constant rate infusion (CRI) of sufentanyl IV. Intra-operatively, assessment of nociception was based on changes in physiological parameters and on the analgesics requirement, whereas in the post-operative period evaluation of pain was performed by using a Hellyer and Gaynor pain score and by comparing the doses of rescue buprenorphine required by the two treatment groups. Although no statistically significant differences in intra-operative sufentanyl doses were found between treatment groups, group C had superior cardiovascular stability, and lower post-operative pain scores and rescue buprenorphine doses than group P. Our results indicate that administration of carprofen prior to surgery was effective in improving peri-operative analgesia in dogs undergoing TPLO.

Epidural Analgesia during Open Radical Prostatectomy Does Not Improve Long-Term Cancer-Related Outcome: A Retrospective Study in Patients with Advanced Prostate Cancer

Background A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking. Methods In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP) with general anesthesia combined with intra- and postoperative epidural analgesia (n=67) or with postoperative ketorolac-morphine analgesia (n=81) were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs). Biochemical recurrence (BCR)-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death. Results The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07). For both groups, higher preoperative PSA (hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.01-1.02, P<0.0001), increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007) and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04) were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001). Conclusions General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs.

Hierarchical segmentation-assisted multimodal registration for MR brain images

Information theory-based metric such as mutual information (MI) is widely used as similarity measurement for multimodal registration. Nevertheless, this metric may lead to matching ambiguity for non-rigid registration. Moreover, maximization of MI alone does not necessarily produce an optimal solution. In this paper, we propose a segmentation-assisted similarity metric based on point-wise mutual information (PMI). This similarity metric, termed SPMI, enhances the registration accuracy by considering tissue classification probabilities as prior information, which is generated from an expectation maximization (EM) algorithm. Diffeomorphic demons is then adopted as the registration model and is optimized in a hierarchical framework (H-SPMI) based on different levels of anatomical structure as prior knowledge. The proposed method is evaluated using Brainweb synthetic data and clinical fMRI images. Both qualitative and quantitative assessment were performed as well as a sensitivity analysis to the segmentation error. Compared to the pure intensity-based approaches which only maximize mutual information, we show that the proposed algorithm provides significantly better accuracy on both synthetic and clinical data.

Multimodal viral communication: a social semiotic analysis of the popular Spanish "Ola ke ase" meme

Multimodality – the interdependence of semiotic resources in text – is an existential element of today’s media. The term multimodality attends systematically to the social interpretation of a wide range of communicational forms used in meaning making. A primary focus of social- semiotic multimodal analysis is on mapping how modal resources are used by people in a given social context. In November 2012 the “Ola ke ase” catchphrase, which is a play on “Hola ¿qué hace?”, appeared for the first time in Spain and immediately has been adopted as a Twitter hashtag and an image macro series. Its viral spread on social networks has been tremendous, being a trending topic in various Spanish-speaking countries. The objective of analysis is how language and image work together in the “Ola ke ase” meme. The interplay between text and image in one of the original memes and some of its variations is quantitatively analysed applying a social-semiotic approach. Results demonstrate how the “Ola ke ase” meme functions through its multimodal character and the non-standard orthography. The spread of uncountable variations of the meme shows the social process that goes on in the meaning making of the semiotic elements.

A Hybrid Model for Multimodal Brain Tumor Segmentation

We present a fully automatic segmentation method for multi-modal brain tumor segmentation. The proposed generative-discriminative hybrid model generates initial tissue probabilities, which are used subsequently for enhancing the classi�cation and spatial regularization. The model has been evaluated on the BRATS2013 training set, which includes multimodal MRI images from patients with high- and low-grade gliomas. Our method is capable of segmenting the image into healthy (GM, WM, CSF) and pathological tissue (necrotic, enhancing and non-enhancing tumor, edema). We achieved state-of-the-art performance (Dice mean values of 0.69 and 0.8 for tumor subcompartments and complete tumor respectively) within a reasonable timeframe (4 to 15 minutes).

Multimodal 3 tesla MRI confirms intact arterial wall in acute stroke patients after stent-retriever thrombectomy

BACKGROUND AND PURPOSE The aim of this prospective study was to assess vascular integrity after stent-retriever thrombectomy. METHODS Dissection, contrast medium extravasation, and vasospasm were evaluated in 23 patients after thrombectomy with biplane or 3D-digital subtraction angiography and 3-Tesla vessel wall MRI. RESULTS Vasospasm was detected angiographically in 10 patients, necessitating intra-arterial nimodipine in 2 of them. Contrast extravasation, intramural hemorrhage, or iatrogenic dissection were not detected on multimodal MRI in any patient even after Y-double stent-retriever technique. CONCLUSIONS Our findings suggest that clinically relevant vessel wall injuries occur rarely after stent-retriever thrombectomy.

White matter matters: a multimodal approach to investigate white matter microstructure and metabolism

White matter connects different brain areas and applies electrical insulation to the neuron’s axons with myelin sheaths in order to enable quick signal transmission. Due to its modulatory properties in signal conduction, white matter plays an essential role in learning, cognition and psychiatric disorders (Fields, 2008a). In respect thereof, the non-invasive investigation of white matter anatomy and function in vivo provides the unique opportunity to explore the most complex organ of our body. Thus, the present thesis aimed to apply a multimodal neuroimaging approach to investigate different white matter properties in psychiatric and healthy populations. On the one hand, white matter microstructural properties were investigated in a psychiatric population; on the other hand, white matter metabolic properties were assessed in healthy adults providing basic information about the brain’s wiring entity. As a result, three research papers are presented here. The first paper assessed the microstructural properties of white matter in relation to a frequent epidemiologic finding in schizophrenia. As a result, reduced white matter integrity was observed in patients born in summer and autumn compared to patients born in winter and spring. Despite the large genetic basis of schizophrenia, accumulating evidence indicates that environmental exposures may be implicated in the development of schizophrenia (A. S. Brown, 2011). Notably, epidemiologic studies have shown a 5–8% excess of births during winter and spring for patients with schizophrenia on the Northern Hemisphere at higher latitudes (Torrey, Miller, Rawlings, & Yolken, 1997). Although the underlying mechanisms are unclear, the seasonal birth effect may indicate fluctuating environmental risk factors for schizophrenia. Thus, exposure to harmful factors during foetal development may result in the activation of pathologic neural circuits during adolescence or young adulthood, increasing the risk of schizophrenia (Fatemi & Folsom, 2009). While white matter development starts during the foetal period and continues until adulthood, its major development is accomplished by the age of two years (Brody, Kinney, Kloman, & Gilles, 1987; Huang et al., 2009). This indicates a vulnerability period of white matter that may coincide with the fluctuating environmental risk factors for schizophrenia. Since microstructural alterations of white matter in schizophrenia are frequently observed, the current study provided evidence for the neurodevelopmental hypothesis of schizophrenia. In the second research paper, the perfusion of white matter showed a positive correlation between white matter microstructure and its perfusion with blood across healthy adults. This finding was in line with clinical studies indicating a tight coupling between cerebral perfusion and WM health across subjects (Amann et al., 2012; Chen, Rosas, & Salat, 2013; Kitagawa et al., 2009). Although relatively little is known about the metabolic properties of white matter, different microstructural properties, such as axon diameter and myelination, might be coupled with the metabolic demand of white matter. Furthermore, the ability to detect perfusion signal in white matter was in accordance with a recent study showing that technical improvements, such as pseudo-continuous arterial spin labeling, enabled the reliable detection of white matter perfusion signal (van Osch et al., 2009). The third paper involved a collaboration within the same department to assess the interrelation between functional connectivity networks and their underlying structural connectivity.

Attitudes of Swiss veterinarians towards pain and analgesia in dogs and cats.

A survey was performed to evaluate the use of perioperative analgesia in dogs and cats by veterinary practitioners. Questions were grouped in seven sections recording personal data, education in veterinary analgesia, general ideology regarding treatment of perioperative pain, personal experience, assessment, and use of main analgesics to treat perioperative pain. A total of 258 received forms were analyzed. Based on 5 questions, 88 % showed excellent motivation to use perioperative pain therapy. The main reason declared for the use of analgesics was to relieve the patient from pain (64.1 %). Most veterinarians reported to routinely administer analgesics before (71 - 96 %) or after (2 - 23 %) surgery. The most used analgesics were non-steroidal anti-inflammatory drugs (carprofen, meloxicam) and opioids (butorphanol, buprenorphine). Animals were routinely evaluated for pain after recovery. Only 43.8 % of veterinarians declared to use loco-regional anaesthesia. Swiss veterinarians appear to recognize well the need for perioperative pain treatment. However, weakness was shown in evaluating pain severity, distinguishing between opioid classes, and using loco-regional anaesthesia.

Multimodal treatment for high-risk prostate cancer with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel and long-term androgen deprivation therapy: results of a prospective phase II trial.

BACKGROUND The optimal management of high-risk prostate cancer remains uncertain. In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer. METHODS This was a prospective phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel-based chemotherapy and long-term androgen deprivation therapy. Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method. RESULTS Acute gastro-intestinal and genito-urinary toxicity was grade 2 in 23% and 20% of patients, and grade 3 in 9% and 3% of patients, respectively. Acute blood/bone marrow toxicity was grade 2 in 20% of patients. No acute grade ≥ 4 toxicity was observed. Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9% of patients each. No late grade ≥ 3 toxicity was observed. Median follow-up was 63 months (interquartile range 31-79). Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55% (95% confidence interval, 35-75%) and 70% (95% confidence interval, 52-88%), respectively. CONCLUSIONS In our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer, toxicity was acceptably low and mid-term oncological outcome was good. This treatment paradigm, thus, may warrant further evaluation in phase III randomized trials.