Assessment and management of perioperative pain in neurosurgical patients

This PhD thesis investigated the assessment and management of pain in a neurosurgical population. A national survey of anesthesiologists in India was conducted to understand practices for pain assessment and management in patients undergoing neurosurgeries. The practices varied, with 50% using structured format for pain assessment/management, and 15% using opioids for postoperative pain relief. To understand the burden of pain after brain surgery in India, a prospective observational study was performed. Two out of three patients reported significant pain during the first three days of surgery. Reporting of pain is not possible under anesthesia. Hence, objective methods are explored. During tracheal intubation, changes in analgesia nociception index, a monitor for intraoperative pain/nociception, were found to correlate with changes in heart rate and blood pressure. Another parameter, the surgical pleth index, also predicted pain and response to analgesics during brain surgery. Non-opioid pain medicines were found to be equivalent to opioids in brain surgery, and superior in spine surgery, in clinical trials and the meta-analysis performed as part of this thesis

A RANDOMIZED CONTROLLED TRIAL OF ANESTHESIA GUIDED BY BIS VS. STANDARD CARE AND EFFECTS ON COGNITION

Postoperative cognitive dysfunction (POCD) occurs frequently in individuals undergoing major surgery with general anesthesia. POCD adversely affects morbidity and health-related quality of life. Derived electroencephalographic (EEG) monitoring is utilized to guide the anesthesia provider in titration of volatile anesthetics. POCD has been associated volatile anesthetic neurotoxicity. EEG monitors are known to reduce a patient’s total cumulative dose exposure to volatile anesthetics. There is currently little evidence to support utilization of EEG monitors as a guide to reduce the incidence of POCD. The purpose of this dissertation was to develop and test a technique of general anesthesia, delivered by anesthesia providers and guided by the Bispectral Index™ (BIS) system EEG monitor. This technique was designed to reduce cumulative volatile anesthetic exposure and reduce cognitive decline. Prior to testing the intervention, preliminary work was conducted resulting in a review of evidence for current concepts in the mechanism of volatile anesthetics and their relationship with POCD. Based on information from these manuscripts, a randomized, controlled study was conducted to test the effects of BIS guided anesthetic technique on outcomes of middle aged patients undergoing impatient major surgery. Eighty-eight patients scheduled for major inpatient surgery were randomized to a BIS guided anesthetic, or to usual care control. Although not in every cognitive domain, BIS guidance resulted in superior and not inferior performance in cognitive testing. The third manuscript documents predictors of cognitive decline. This was a secondary, planned data analysis of the previous prospective, randomized controlled trial. Consistent predictors of cognitive decline through the study phases were older age, lower income, and lower education. In addition to these, tobacco abuse is a significantly predictive characteristic. Further research should be focused on at risk cognitive domains, as well as, exploring other anesthetic regimens to avoid cognitive decline

Sleep-time predictors of cardiovascular complications in surgical peripheral arterial disease

ABSTRACT Patients with peripheral arterial disease (PAD) undergoing surgical revascularisation are in high risk of postoperative cardiovascular complications and death, due to advancing age and multiple comorbidities in the population. In addition, PAD needing surgery represents a severe form of systemic atherosclerosis but the exact underlying pathophysiology of acute myocardial infarction (AMI) in these patients is unclear and predicting outcome especially in the long-term is challenging. Obstructive sleep apnoea (OSA) is increasingly common in the general population and independently associated with various manifestations of cardiovascular disease or their risk factors; OSA is highly prevalent in patients with coronary artery disease (CAD), stroke, hypertension and diabetes. To expand this knowledge, we determined the prevalence and severity (in terms of the apnoeahypopnoea index, AHI) of OSA in surgical PAD as well as its impact on the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) in this patient group. Heart rate variability (HRV) reflects fluctuations in sympathetic and parasympathetic activation responsible for neurocirculatory control in various physiological and pathophysiological situations. Depressed HRV is associated with increased cardiovascular morbidity and mortality following AMI and major surgery. In this study, the alterations of nocturnal HRV and their association with the severity of OSA and incidence of MACCE in patients with PAD was assessed, including the fractal correlation properties of HRV. HRV in a control group of 15 healthy subjects was also examined. Patients scheduled for sub-inguinal vascular surgery (n=84, age 67±9 years) underwent polysomnography and HRV analyses. OSA was detected in 86% of patients and in 56% it was moderate or severe. Age, male gender, depressed left ventricular function and decreasing high density lipoprotein/cholesterol ratio (HDL/Chol) predicted the presence and severity of OSA. The latter two remained significant after adjusting for age and gender. OSA with AHI ≥20/hour, used as a cut-off in the outcome analyses, predicted a higher risk of MACCE (p=0.001) along with pre-existing CAD (p=0.001), decreasing HDL/Chol (p=0.048) and <4 years history of PAD (p=0.018). HRV was altered in patients with PAD when compared to controls but the time domain measures were mostly unchanged. In the frequency domain, low frequency power was generally lower, high frequency power was mostly higher and fractal correlation was consistently lower. Very low frequency power was increased the most in patients with AHI 10-20/hour when compared to <10/hour while those with AHI ≥20/hour had lower fractal correlation in the morning. Patients suffering a MACCE had lower high frequency power during S3-4 and rapid eye movement sleep. In conclusion, OSA is associated with worsening atherosclerosis and predicts MACCE after vascular surgery. HRV alterations, although associated with PAD, have limited predictive value. Keywords: atherosclerosis, peripheral arterial disease, sleep apnoea, heart rate variabilityTIIVISTELMÄ Unenaikaiset sydänkomplikaatioiden ennustetekijät kirurgista hoitoa vaativassa perifeerisessä valtimotaudissa Perifeeristä valtimotautia sairastavilla potilailla on suuri leikkauksenjälkeisten sydänkomplikaatioiden riski johtuen yhä iäkkäämmästä väestöstä sekä lukuisista rinnakkaissairauksista. Lisäksi perifeerinen valtimotauti merkitsee vaikea-asteista yleistynyttä ateroskleroosia, mutta sydäninfarktin tarkka syntymekanismi näillä potilailla on epäselvä ja erityisesti pitkän aikavälin ennusteen arviointi on haastavaa. Obstruktiivinen uniapnea yleistyy väestössä ja sillä on itsenäinen yhteys useisiin sydän- ja verisuonisairauksiin ja niiden riskitekijöihin; uniapnea on erittäin yleinen sepelvaltimotauti-, aivohalvaus-, verenpainetauti- ja diabetespotilailla. Tämän tietopohjan laajentamiseksi tässä tutkimuksessa määritettiin uniapnean esiintyvyys ja vaikeusaste (määrittäjänä apnea-hypopneaindeksi, AHI) vaikea-asteista yleistynyttä ateroskleroosia sairastavilla potilailla sekä sen vaikutus vakavien sydän- ja aivotapahtumien ilmaantuvuuteen. Sydämen sykevaihtelu kuvastaa autonomisen hermoston toiminnan muutoksia, jotka puolestaan vastaavat verenkierron säätelystä erilaisissa fysiologisissa ja patofysiologisissa tilanteissa. Alentunut sykevaihtelu on yhteydessä lisääntyneeseen kardiovaskulaariseen sairastuvuuteen ja kuolleisuuteen sairastetun sydäninfarktin tai suuren leikkauksen jälkeen. Tässä tutkimuksessa arvioitiin yöllisen sydämen sykevaihtelun muutosten yhteyttä uniapnean vaikeusasteeseen sekä vakavien sydän- ja aivotapahtumien ilmaantuvuuteen, mukaan lukien sykevaihtelun fraktaalikorrelaatio-ominaisuudet. Tutkimuksessa analysoitiin sykevaihtelu myös 15 terveen henkilön vertailuryhmältä. Nivustason alapuoliseen verisuonileikkaukseen meneville potilaille (n=84, ikä 67±9 vuotta) tehtiin unipolygrafia ja sykevaihteluanalyysi. Uniapnea todettiin 86 %:lla potilaista ja 56 %:lla se oli kohtalainen tai vaikea. Ikä, miessukupuoli, heikentynyt vasemman kammion toiminta ja alentunut HDL-kolesterolin suhde kokonaiskolesteroliin ennustivat uniapneaa ja sen vaikeutumista; 2 viimeksi mainittua säilyivät merkitsevinä ikä- ja sukupuolivakioinnin jälkeen. AHI ≥20/tunti, joka valittiin kynnysarvoksi päätetapahtumaanalyyseihin, ennusti merkitsevästi vakavia sydän- ja aivotapahtumia (p=0.001). Muita merkitseviä tekijöitä olivat sepelvaltimotauti (p=0.001), alentunut HDL-suhde (p=0.048) ja lyhyt (alle 4 vuotta) perifeerisen valtimotaudin kesto ennen leikkaushoidon tarvetta (p=0.018). Sykevaihtelu oli muuttunut valtimotautipotilailla verrattuna kontrolleihin, mutta aikakenttäparametrit säilyivät lähes ennallaan. Pienitaajuuksinen sykevaihtelu oli yleisesti vähäisempää, suuritaajuuksinen enimmäkseen voimakkaampaa ja fraktaalikorrelaatio johdonmukaisesti heikompaa. Hyvin pienitaajuuksinen vaihtelu oli eniten lisääntynyt AHI 10-20/tunti -alaryhmässä verrattuna AHI <10/tunti -ryhmään, mutta AHI ≥20/tunti -potilailla aamun fraktaalikorrelaatio oli heikompaa. Potilaiden, jotka saivat vakavia sydän- ja aivotapahtumia, suuritaajuusvaihtelu oli heikompaa syvän unen ja vilkeunen aikana. Johtopäätöksinä todetaan, että uniapnea on yhteydessä vaikeutuvaan valtimotautiin sekä ennustaa vakavia sydän- ja aivotapahtumia verisuonileikkauksen jälkeen sykevaihtelun muutosten ennustearvon ollessa tässä aineistossa hyvin rajallinen. Avainsanat: ateroskleroosi, perifeerinen valtimotauti, uniapnea, sykevaihtel

Data mart based research in heart surgery

Arnrich B. Data mart based research in heart surgery. Bielefeld (Germany): Bielefeld University; 2006.The proposed data mart based information system has proven to be useful and effective in the particular application domain of clinical research in heart surgery. In contrast to common data warehouse systems who are focused primarily on administrative, managerial, and executive decision making, the primary objective of the designed and implemented data mart was to provide an ongoing, consolidated and stable research basis. Beside detail-oriented patient data also aggregated data are incorporated in order to fulfill multiple purposes. Due to the chosen concept, this technique integrates the current and historical data from all relevant data sources without imposing any considerable operational or liability contract risk for the existing hospital information systems (HIS). By this means the possible resistance of involved persons in charge can be minimized and the project specific goals effectively met. The challenges of isolated data sources, securing a high data quality, data with partial redundancy and consistency, valuable legacy data in special file formats, and privacy protection regulations are met with the proposed data mart architecture. The applicability was demonstrated in several fields, including (i) to permit easy comprehensive medical research, (ii) to assess preoperative risks of adverse surgical outcomes, (iii) to get insights into historical performance changes, (iv) to monitor surgical results, (v) to improve risk estimation, and (vi) to generate new knowledge from observational studies. The data mart approach allows to turn redundant data from the electronically available hospital data sources into valuable information. On the one hand, redundancies are used to detect inconsistencies within and across HIS. On the other hand, redundancies are used to derive attributes from several data sources which originally did not contain the desired semantic meaning. Appropriate verification tools help to inspect the extraction and transformation processes in order to ensure a high data quality. Based on the verification data stored during data mart assembly, various aspects on the basis of an individual case, a group, or a specific rule can be inspected. Invalid values or inconsistencies must be corrected in the primary source data bases by the health professionals. Due to all modifications are automatically transferred to the data mart system in a subsequent cycle, a consolidated and stable research data base is achieved throughout the system in a persistent manner. In the past, performing comprehensive observational studies at the Heart Institute Lahr had been extremely time consuming and therefore limited. Several attempts had already been conducted to extract and combine data from the electronically available data sources. Dependent on the desired scientific task, the processes to extract and connect the data were often rebuilt and modified. Consequently the semantics and the definitions of the research data changed from one study to the other. Additionally, it was very difficult to maintain an overview of all data variants and derived research data sets. With the implementation of the presented data mart system the most time and effort consuming process with conducting successful observational studies could be replaced and the research basis remains stable and leads to reliable results

General Anesthesia as a Multimodal Individualized Clinical Concept

In this book, a series of modern multimodal monitoring techniques during general anesthesia are presented, with a focus on patient-oriented anesthesia based on the individual needs of each patient reflected in the degree of hypnosis, the nociception–antinociception balance, and neuromuscular transmission. Moreover, a series of secondary implications for hemodynamic status, post-anesthetic recovery, and patient satisfaction are highlighted

ONE VOICE Training to Enable Nurses and Anesthesia Providers to Mitigate Pediatric Presurgical Anxiety

ABSTRACT ONE VOICE Training to Enable Nurses and Anesthesia Providers to Mitigate Pediatric Presurgical Anxiety Sarah E. Hinnant Background: Children in the preoperative area experience presurgical anxiety at rates of up to seventy-five percent. Increased pediatric anxiety is directly linked to increased anesthetic requirements, increased risk for development of emergence delirium, and increased time spent in the post anesthesia care unit. Numerous high-quality studies show that intervention by a certified child life specialist mitigates preoperative pediatric anxiety. Often child life specialists are not available to meet with all children prior to surgery. Registered nurses (RNs) and certified registered nurse anesthesiologists (CRNAs) are present in the presurgical area and have the potential to reduce pediatric presurgical anxiety. Purpose: The purpose of this quality improvement project was to increase provider adherence to the ONE VOICE intervention and to reduce pediatric presurgical anxiety. Methods/Interventions: This prospective quality improvement project used an unpaired cohort design to evaluate the effectiveness of the ONE VOICE intervention on pediatric presurgical anxiety. A group of trained raters used the modified Yale Preoperative Anxiety Scale-short form (m-YPAS-sf) to assess baseline anxiety. Pediatric RNs and CRNAs completed a self-assessment of baseline adherence to the ONE VOICE intervention. Then the RNs and CRNAs were trained on the ONE VOICE intervention. After one month, the RNs and CRNAs took the self-assessment again. Next, post intervention pediatric anxiety was assessed using the m-YPAS-sf. Results: Implementation of the ONE VOICE teaching mnemonic led to a statistically significant increase in RN and CRNA adherence to ‘educating the child before the procedure about what is going to happen.’ A self-assessment Likert survey distributed via Qualtrics survey software, pointed to a clinically significant increase in adherence of seven of the eight ONE VOICE components. Pediatric anxiety in the presurgical area at West Virginia University Medicine (WVUM) Children’s was reduced by 28.3%. Conclusion: Use of the m-YPAS-sf in the preoperative area at WVUM Children’s would allow more metrics to be evaluated. Medication requirement, length of stay, incidence of emergence delirium, and development of pediatric medical traumatic stress are areas of study showing a correlation to pediatric presurgical anxiety. Continued evaluation of this project should focus on measuring the impact of the ONE VOICE intervention on medication requirement, length of stay, and the incidence of emergence delirium

Developing Predictive Models for Risk of Postoperative Complications and Hemodynamic Instability in Patients Undergoing Surgery

Patients undergoing high-risk surgeries are often at higher risk of developing hemodynamic instability during surgery resulting in poor postoperative outcomes. This is usually associated with significantly increased postoperative morbidity and mortality, which therefore makes the early identification of these critical events and those patients at risk of postoperative complications crucial. With these motivations in mind, we first created a large deidentified research dataset of surgical case medical records from University of California, Irvine Medical Center (UCIMC) matched with physiological waveforms as well as intermittent vital sign values, lab values, and ventilator settings. To our knowledge, such a dataset does not currently exist for the intraoperative environment. We hope that creating a such a dataset will allow for advances in machine learning for intraoperative care. Using medical data from UCLA, we have developed deep neural network models to classify the risks of postoperative mortality, acute kidney injury, and reintubation utilizing readily available intraoperative information. Our risk scores were compared to currently commonly used risk indices ASA and Surgical Apgar as well as logistic regression. While the deep neural network models performed better than the risk scores and logistic regression, clinicians require additional information to assess what led to increased risk of complications. To address this, we also assessed the use of generalized additive neural networks (GANNs) to create a graphical look at how different features contributed to the risk of in hospital mortality. Finally, we were also interested in predicting critical intraoperative events to allow for time for the clinician to avoid such events. We focused on intraoperative hypotension as it is easier to define and has been shown to lead to increased risk of acute kidney injury, stroke, and myocardial injury. For the hypotension prediction models, we looked at the arterial pressure waveform and EMR data as inputs. Overall, these aims address a gap in current clinical decision guidance and support to reduce adverse events during surgery as well complications after

Radiological evaluation of biomarkers for renal cell carcinoma

Role of MRI DWI sequences in the evaluation of early response to neo- angiogenesis inhibitors in metastatic renal cell carcinoma Purpose: Angiogenesis inhibitors have a potential role in treating metastatic renal cell carcinoma, but it is still not clear why some patients don't respond. Our objective was to look for DWI parameters able to identify patients with metastatic renal cell carcinoma who would not benefit from target therapy. RECIST1.1 was considered as Reference Standard. Methods & Materials: We prospectively enrolled 43 patients candidate to start angiogenesis inhibitors with at least one target lesion and who underwent 1,5T MRI examination with multiple bvalues DWI sequences (0,40,200,300,600): one week before (t0), 2 weeks after (t2) and 8 weeks (t8) after treatment beginning. ADC value was calculated drawing ROIs on 3 different planes. 33 patients with 38 lesions had suitable data for comparative evaluation. Results: At T8 follow-up 9 patients had partial response (PR), 20 table disease (SD), 4 progression disease (PD); average progression free survival was 272 days. PD group, as compared to DC or to PR showed significantly lower ADC values at b40 at t0 (p<0.05): we can assess that more vascularised lesions are more responsive to treatment. PD group have significantly lower ADC values then both other groups, at t0, t2 and t8, for all b-values (p<0.05). PFS and OS correlates well with ADC, in particular OS with ADC b40 at t0 (r=0,69). Coclusions: Results show that PD group has significantly lower ADC values than PR or DC everytime (t0, t2, t8) At t0 there is a better correlation between PFS or OS & ADC than PFS & dimensional criteria. ADC at t0 may help selecting patients with promising good response to angiogenesis inhibitors. Moreover at t0 and at t2 ADC has the potential to select patients who wouldn't benefit from angiogenesis inhibitors Nowadays, in the era of target therapy, it is crucial to select patients potentially responders. We have to look at cost/benefit ratio and at increasing costs of treatment options. DWI has the potential role to identify patients whose's tumor wouldn't benefit from target therapy, adding a value (ADC) to other imaging (e.g. DCE-MRI, texture imaging) and clinical parameters (e.g. miRNA) in a hypothetic multiparametric analysis.CT Texture Analysis in Clear Cell Renal Cell Carcinoma: a Radiogenomics Prospective Purpose: The aim of this study was to investigate whether quantitative parameters obtained from CT Texture Analysis (CTTA) correlate with expression of miRNA in clear cell Renal Cell Carcinoma (ccRCC). Methods and Materials: In a retrospective single centre study, multiphasic CT examination (with arterial, portal, equilibrium and urographic phases) was performed on 20 patients with clear cell renal carcinomas (14 men and 6 women; mean age 65 years ± 13). Measures of heterogeneity were obtained in post-processing by placing a ROI on the entire tumour and CTTA parameters such as entropy, kurtosis, skewness, mean, mean of positive pixels, and SD of pixel distribution histogram were measured using multiple filter settings. Quantitative data were correlated with the expression of miRNAs obtained from the same cohort of patients: 8 fresh frozen samples and 12 formalin-fixed paraffin-embedded samples (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both evaluations (miRNAs and CTTA) were performed on tumour tissues as well as on normal cortico-medullar tissues. Analysis of Variance with linear multiple regression model methods were obtained with SPSS statistic software. For all comparisons, statistical significance was assumed p<0.05 Results: We evidenced that CTTA has robust parameters (e.g. entropy, mean, sd) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression (R2 =0,25) was evidenced in tumour tissues as compared to normal tissues (R2 =0,15). Interestingly, excluding four patients with extreme over-expression of miR-21-5p, excellent relation between entropy and miR21-5p levels was found specifically in tumour samples (R2= 0,64; p<0.05). Conclusion: Entropy and miRNA-21-5p show promising correlation in ccRCC; in addiction CTTA features, in particular mean and entropy show a statistically significant increase in ccRCC as compared with normal renal parenchyma