SAMMANFATTNING Titel: Sederingens betydelse för utvecklingen av ventilator associerad pneumoni hos intensivvårdspatienter. Fakultet: Hälsa, natur- och teknikvetenskap Kurs: Examensarbete - omvårdnad, 15 hp Författare: Sanna Willford Handledare: Anna Nordin Examinerande lärare: Inger James Examinator: Jan Nilsson Sidor: 32 Datum för examination: Juni 2022 Nyckelord: Pneumoni, ventilator associerad, Sedering, Intensivvård Introduktion: Ventilator associerad pneumoni (VAP) är en vårdrelaterad infektion som klassas som en vårdskada och som skapar ett vårdlidande för patienten. Vårdskador kan undvikas om rätt åtgärder vidtas av hälso- och sjukvården. Sedering är grundläggande för säkerhet och bekvämlighet hos respiratorbehandlade patienter. Utvecklingen av VAP förekommer oftare hos patienter som får kontinuerlig sedering än hos patienter som har en daglig sederingspaus. Även andra interventioner i sederingen kan ha betydelse för utvecklingen av VAP. Syfte: Syftet med denna studie var att undersöka sederingens betydelse för utvecklingen av VAP hos respiratorbehandlade patienter på IVA. Metod: I denna systematiska litteraturstudie har en narrativ sammanställning av kvantitativa studier genomförts. En induktiv innehållsanalys enligt Bettany-Saltikov och McSherrys niostegs modell samt SBUs riktlinjer för litteraturstudier har använts. Litteraturstudiens resultat har bedömts med GRADE. Resultat: Flera av de inkluderade studierna såg en statistisk signifikant minskning i antalet patienter som utvecklade VAP, trots att de använde sig av olika interventioner i sederingen. Förändringar i sederingsstrategi, sederingsgrad, val av sederande läkemedel och personalens följsamhet i de VAP preventiva interventionerna var av betydelse. Konklusion: Olika interventioner gällande sederingen har betydelse för utvecklingen av VAP. Att minska förekomsten av VAP kan förkorta tiden för respiratorbehandling, förkorta vårdtiden, minska mortaliteten och minska vårdkostnader. / ABSTRACT  Title: The significance of sedation for the development of ventilator-associated pneumonia in intensive care patients. Faculty: Health, Science and Technology  Course: Degree project - nursing, 15 ECTS  Authors: Sanna Willford Supervisor: Anna Nordin Examiner: Inger James Examiner: Jan Nilsson Pages: 32 Date for the examination: June 2022 Key words: Pneumonia, ventilator-associated, Sedation, Intensive care Introduction: Ventilator associated pneumonia (VAP) is a healthcare-associated infection that is classified as a healthcare injury and that creates a patient suffering. Healthcare injuries can be avoided if the right measures are taken by the health service. Sedation is essential for the safety and comfort of respiratory patients. The development of VAP occurs more often in patients who receive continuous sedation than in patients who have a daily sedation break. Other interventions in sedation can also be important for the development of VAP. Aim: The aim of this study was to investigate the significance of sedation for the development of VAP in ventilator-treated patients at IVA. Method: In this systematic literature study, a narrative compilation of quantitative studies has been conducted. An inductive content analysis according to Bettany-Saltikov and McSherry's nine-step model and SBU's guidelines for literature studies have been used. The results of the literature study have been assessed with GRADE. Results: Several of the included studies saw a statistically significant reduction in the number of patients who developed VAP, despite the fact that they used different interventions in sedation. Changes in sedation strategy and degree of sedation affected the presence of VAP. The choice of sedative drugs and the staff's compliance in the VAP preventive interventions were also important. Conclusion: Various interventions regarding sedation are important for the development of VAP. Reducing the incidence of VAP can shorten the time of ventilator treatment, shorten the care time, reduce mortality and reduce care costs.

Aims: The purpose of this thesis was to synthesize the current literature on alpha amylase as an emerging biomarker of microaspiration in mechanically ventilated patient. Methods: The methodology included a review and synthesis of pertinent research articles from 1981-2018, written in English language. Criteria for inclusion in the review were all articles that evaluated α- amylase in tracheal secretions or bronchoalveolar lavage fluid (BAL) as a diagnostic tool for identifying microaspiration. The search yielded 11 studies that were reviewed. Findings: The findings suggest that once aspiration occurs, the duration of α-amylase in the lungs requires further exploration to assist in interpretation of positive values. After these values are identified they need be used consistently used throughout practice of mechanically ventilated patients. Inconsistencies in the defining parameters of α-amylase were used with the thirteen studies. Conclusion: Testing amylase levels can require financial stability, standardized training, and timeliness of collecting the specimen. Alpha-amylase is a biomarker of microaspiration. Further research should be conducted to evaluate the biomarker capabilities of α-amylase to assist in early identification and/or prevention of microaspiration in mechanically ventilated patients. Implications for nursing policy practice, education, and considerations for upcoming research of α-amylase were reviewed with limitations to the study.

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Ventilator-associated pneumonia (VAP) has been attributed with lengthening patients' stay in the intensive care unit (ICU), is the leading cause of death among nosocomial infections, and leads to increased hospital cost. Various positional strategies in the prevention of VAP include head of bed (HOB) elevation, continuous lateral rotation therapy (CLRT), and kinetic bed therapy. However, poor compliance rates in critical care units have been reported. Mechanically ventilated patients develop nosocomial pneumonia at a rate 6 to 21 times greater than non-ventilated hospitalized patients. A HOB elevation of 30' to 45' and the turning of patients every two hours are two commonly accepted guidelines used to prevent respiratory compilations by facilitating the clearance of pulmonary secretions. Both HOB elevation and CLRT were explored as interventions that could be implemented to reduce the incidence of VAP. It is difficult to attribute reduced VAP rates to either modality alone. However, when HOB elevation and CLRT are utilized in concert with other modalities, clinically significant benefits become readily apparent. Implementation of both improves clinical outcomes. These modalities should not be considered as individual strategies to reduce VAP, but as part of a comprehensive approach to reduce the incidence of VAP and improve patient outcomes.

Ventilator associated pneumonia (VAP) is a nosocomial infection that is acquired in critically ill patients 48 hours or more after intubation. Many interventions have been studied to reduce or prevent patients from acquiring VAP. This integrated literature review examines empirical evidence related to suctioning techniques that reduce or prevent the acquisition of VAP. Oral and subglottic secretion suctioning were examined in depth. It is concluded that the intervention of oral and subglottic secretion suctioning was shown to reduce the incidence of VAP in adult patients.

Récemment, les microbiotes pulmonaires bactériens d’un nombre très limité de patients atteints de mucoviscidose et de pneumopathies acquises sous ventilation mécanique (PAVM) ont été étudiés en utilisant l'amplification du gène 16S rDNA bactérien suivie par la construction de librairies de clones et différentes approches de séquençage. Ces études ont montré que la population microbienne de patients atteints de maladies respiratoires était plus diversifiée que prévue. Dans l'étude actuelle, nous utilisons une approche comparable pour identifier exhaustivement les agents pathogènes (bactéries, virus, et champignons) composant le microbiote pulmonaire associé aux pneumopathies développées en unités de réanimation. L'étude a inclus des patients admis en réanimation et présentant des formes de pneumopathies acquises sous ventilation mécanique (n = 106), de pneumopathies communautaires (n = 32), de pneumopathies nosocomiales sans ventilation mécanique (n = 22) et de pneumopathies d’aspiration (n = 25). Une cohorte de 25 patients admis en réanimation et ne présentant pas de symptômes de pneumopathie a été étudiée comme contrôle. Cette première partie du travail amènera ainsi à réaliser un catalogue exhaustif des agents de pneumopathies nosocomiales ; à connaître la prévalence des agents identifiés et d’identifier les co-infections fréquemment observées, et surtout à vérifier si ces agents peuvent être identifiés ou pas dans les prélèvements respiratoires profonds de patients non symptomatiques. Pour réaliser cette partie du travail, des séries de prélèvements, incluant des prélèvements de lavage broncho-alvéolaire (LBA), des prélèvements de sang et d'urine ont été étudiés. Ces prélèvements ont été testés par des moyens d’identification moléculaire moderne basés sur l’amplification de gènes conservés (gènes16S rDNA des bactéries et gène 18S rDNA des champignons) suivie par clonage et séquençage à grande échelle. D’autres pathogènes atypiques sont ciblés par des tests de PCR avec utilisation d’amorces spécifiques. Nous avons également inclus la culture, la co-culture d’amibes, la détection sérologique d'anticorps dirigés contre des agents sélectionnés et des tests d'antigène urinaire, afin de comparer ces tests de routine aux approches moléculaires. Comme résultats, les tests moléculaires nous ont permis d’identifier un vaste répertoire de 160 espèces bactériennes dont 73 n'ont jamais été précédemment rapportées à l’étiologie des pneumopathies. En outre, nous avons trouvé 37 phylotypes bactériens potentiellement nouveaux. Nous avons également identifié 24 espèces de champignons dont 6 n'ont pas été précédemment rapportées à l’étiologie des pneumopathies, 7 virus et étonnamment 6 espèces de plantes. De plus, certains agents pathogènes considérés comme typiques aux pneumopathies nosocomiales tels que Pseudomonas aeruginosa et des Streptococci ont été détectés chez les contrôles comme chez les patients. Cet étonnant résultat souligne l'existence d'un noyau de microbiote pulmonaire.Dans un deuxième travail, faisant suite aux travaux effectués dans notre laboratoire et qui ont pu mettre en évidence que 19% des pneumopathies nosocomiales étaient déterminées par des microorganismes associés aux amibes (MAAs) de l’eau préalablement ignorés ou négligés, nous avons utilisé un test d'immunofluorescence multiplexe pour tester la prévalence des anticorps contre les MAAs dans le sang de patients admis en réanimation et atteints de pneumopathies et la comparer à la prévalence au moment de l'admission. Comme résultat, nous démontrons que certains MAAs peuvent être plus fréquemment détectés après des épisodes de pneumopathies nosocomiales que lors de l’admission. En outre, la réponse immunitaire aux MAAs semble augmenter lorsque le séjour en réanimation est prolongé. Enfin, nous avons mis au point une stratégie de metagénomique pour tester les prélévements pour lesquels aucune étiologie n’a été retrouvée. [...] / Recently, bacterial microbiota from a limited number of patients with cystic fibrosis and ventilator-associated pneumonia (VAP) was studied using 16S rDNA gene amplification followed by clone libraries construction and sequencing. These studies have showed that the microbial population of patients with respiratory infections was more diverse than expected. In the current study, we use a similar approach to identify exhaustively the pathogens (bacteria, viruses, and fungi) comprising the microbiota associated with episodes of pneumonia developed in the intensive care units (ICU). Our study included patients admitted to ICUswith with episodes of ventilator-associated pneumonia (n = 106), community-acquired pneumonia (n = 32), nosocomial pneumonia without mechanical ventilation (n = 22) and aspiration pneumonia (n = 25). A cohort of 25 patients admitted to ICUs without symptoms of pneumonia were studied as controls. This first part of the work enables to prepare an exhaustive repertoire of nosocomial pneumonia pathogenes; to know the prevalence of the pathogens identified and to identify co-infections frequently observed, and especially to ascertain whether these agents can be identified or not in the respiratory samples of patients without symptoms of pneumonia. To perform this part of work, series of samples, including bronchoalveolar lavage (BAL) samples, blood samples and urine samples were collected. These samples were tested by means of modern molecular tools based on the amplification of conserved genes (bacterial 16S rDNA and fungal 18S rDNA genes), followed by highthroutput cloning and sequencing. The atypical pathogens are targeted by PCR tests using specific primers and probes. We also included culture, amoeba co-culture, serological detection of antibodies against selected agents and urinary antigen testing, to compare these routine tests to molecular approaches. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 were never previously reported in pneumonia samples. Moreover, we found 37 putative new bacterial phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia, 7 viruses and surprisingly 6 plant species. Some pathogens considered being typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species may be detected as commonly in controls as in pneumonia patients which strikingly highlight the existence of a core of pulmonary microbiota.In a second work, following previous works performed in our laboratory which were able to show that 19% of nosocomial pneumonia were determined by micro-organisms associated to amoebae (AAMs) previously ignored or neglected, we used a recent test based on multiplex serology to test for the prevalence of antibodies against the AAMs in the blood of patients admitted to ICU and developed episodes of pneumonia and compare it to the prevalence at the time of admission (controls). As a result, we demonstrate that some AAMs may be more frequently detected after episodes of nosocomial pneumonia than at the admission. In addition, the immune response to AAMS appears to increase when the ICU stay is prolonged.Finally, in order to explore samples for which no microbial aetiology was found, we have developed a subtractive hybridization metagenomic strategy and tested it on different clinical samples. The sensitivity of this strategy was also evaluated. We have demonstrated that our method, based on the detection of DNA and RNA of microorganisms in a single test, allows sensitive detection of different types of microorganisms.

Pneumonia associada à ventilação mecânica (PAV) é uma infecção relacionada à assistência à saúde que tem desafiado os órgãos de controle de infecção hospitalares por estar associada a altas taxas de mortalidade e grandes desafios em relação à sua prevenção. Pesquisas buscam encontrar meios para diminuir taxas de PAV e consequentemente reduzir tempo de internação e custos hospitalares. Este presente estudo teve como objetivo principal identificar a etiologia bacteriana pulmonar da PAV correlacionando com as bactérias patogênicas da cavidade bucal, em pacientes submetidos à higiene oral (HO) com clorexidina 0,12%. Foram realizados cultura quantitativa do aspirado traqueal (AT) e cultura da cavidade bucal (CB) em pacientes diagnosticados com PAV, em 10 leitos da Unidade de Terapia Intensiva do Hospital Regional de Gurupi Tocantins. No período de 1 ano a amostra consistiu de 30 pacientes, sendo que 18 foram submetidos à HO com clorexidina e 12 à HO com água destilada. No grupo clorexidina, 5 pacientes (27,7%) apresentaram CB positiva contra 12 do grupo água destilada (100%). Em relação ao AT, 17 pacientes apresentaram cultura positiva com a seguinte frequência: Pseudomonas aeruginosa (21,4%), Citrobacter freundii (21,4%), Acinetobacter baumanni (14,2%), Hafnia alvei (14,2%), Klebsiella sp (14,2%), Burkholderia cepacia (7,4%) e Enterobacter asburial (7,4%). Em 2 pacientes foi encontrado o mesmo microrganismo tanto no AT quanto na CB (Citrobacter freundii). Concluiu-se que a cavidade bucal pode ser um reservatório de potenciais patógenos da PAV e a clorexidina 0,12% pode ser um método eficaz de controle bacteriano neste ambiente. / Ventilator-associated pneumonia (VAP) is a health-care-related infection that has challenged hospital infection control agencies because it is associated with high mortality rates and major challenges in preventing it. Researches seek to find ways to reduce VAP rates and consequently reduce length of hospital stay and hospital costs. This study aimed to identify the pulmonary bacterial etiology of PAV correlating with pathogenic bacteria of the oral cavity in patients submitted to oral hygiene (OH) with chlorhexidine 0.12%. Quantitative culture of the tracheal aspirate (AT) and culture of the buccal cavity (BC) were performed in patients diagnosed with VAP, in 10 beds of the Intensive Care Unit of the Regional Hospital of Gurupi - Tocantins. In the 1-year period the sample consisted of 30 patients, 18 of whom were submitted to OH with chlorhexidine and 12 to OH with distilled water. In the chlorhexidine group, 5 patients (27,7%) presented positive BC versus 12 in the distilled water group (100%). In relation to AT, 17 patients presented a positive culture with the following frequency: Pseudomonas aeruginosa (21,4%), Citrobacter freundii (21,4%), Acinetobacter baumanni (14,2%), Hafnia alvei (14.2%), Klebsiella sp (14,2%), Burkholderia cepacia (7,4%) and Asburial Enterobacter (7,4%). In 2 patients the same microorganism was found in both, AT and BC (Citrobacter freundii). It was concluded that the oral cavity may be a reservoir of potential PAV pathogens and 0,12% chlorhexidine may be an effective method of bacterial control in this environment.

Base teórica: Muitos pacientes internados em Unidade de Terapia Intensiva (UTI) necessitam da instituição da ventilação mecânica invasiva (VM). Porém esta pode trazer efeitos deletérios como: alteração na higiene brônquica e pneumonia associada à ventilação mecânica (PAV). Devido a isso, faz-se necessária avaliação de técnicas de higiene brônquicas eficazes e o menos deletérias possíveis. Objetivos: Comparar a eficácia das técnicas em estudo: vibrocompressão (VB) (G1), hiperinsuflação com o ventilador mecânico (HMV) (G2) VB + HMV (G3) na quantidade de secreção aspirada (SEC), no tempo de VM, na incidência de PAV, na reintubação orotraqueal (Re-IoT) e na mortalidade de pacientes em VM. Método: Ensaio clínico randomizado, realizado no Centro de Terapia Intensiva do Hospital de Clínicas de Porto Alegre (HCPA). Foram incluídos no estudo 93 pacientes (29 G1, 32 G2 e 32 G3) em VM por mais de 24 horas. Foram aplicadas as seguintes técnicas: aspiração isolada (ASP), VB, HMV e VB + HMV. Foram medidas as seguintes variáveis: frequência cardíaca (FC), frequência respiratória (FR), pressão arterial média (PAM), saturação arterial periférica de oxigênio (SpO2), pressão inspiratória de pico (PIP), volume corrente (VC), complacência dinâmica (Cdyn), peso da SEC; tempo de VM, Re-IoT, incidência de PAV e mortalidade na VM. Conclusão: O grupo 3 foi o único que apresentou aumento significativo da SEC, quando comparado à ASP (0,7 g (0,1-2,5) vs 0,2 g (0,0-0,6) – p = 0,006). Em comparação com os demais grupos, o grupo 2 apresentou aumento significativo na incidência de PAV (22% - p = 0,003) e Re-IoT (21,9% - p = 0,048), demonstrando assim, na amostra estudada, que VB + HMV é mais eficaz quanto à quantidade de SEC e exerce efeito protetor, juntamente com a VB, na incidência de PAV e Re-IoT. / Background: Many patients admitted to the Intensive Care Unit (ICU) require the institution of invasive Mechanical Ventilation (MV). However, this can bring harmful effects such as changes in mucociliary transport and cough capacity, leading to bronchial obstruction and Ventilator Associated-Pneumonia (VAP). Objective: To compare the efficacy of the techniques: Vibrocompression (G1), Hyperinflation with Mechanical Ventilation (G2) Vibrocompression + Hyperinflation with Mechanical Ventilation (G3) in the amount of Aspirated Secretions (AS), MV time, the incidence of VAP, Re-intubation tracheal (Re-IoT) and mortality of patients on MV. Method: Randomized clinical trial, conducted at the Intensive Care Unit, of the Hospital de Clinicas de Porto Alegre (HCPA). 93 patients were included in the study (29 G1, 32 G2 and 32 G3) in mechanical ventilation for more than 24 hours. The following techniques were applied: Isolated Aspiration (ASP), Vibrocompression (VB), Hyperinflation with Mechanical Ventilation (HMV) Vibrocompression + Hyperinflation with Mechanical Ventilation (HMV + VB). The following variables were measured: Heart Rate (HR), Respiratory Rate (RR), Mean Arterial Pressure (MAP), Peripheral Arterial Oxygen Saturation (SpO2); Peak Inspiratory Pressure (PIP), Tidal Volume (TV); Dynamic Compliance (Cdyn); weight of the AS; VM time; Re-IoT; VAP incidence and mortality in the VM. Conclusion: The HMV + VB (G3) was the only group that showed significant increase in the AS (0.7 g (0.1-2.5) vs 0.2 g (0.0-0.6) – p = 0.006) when compared to ASP. Compared with the other groups G2 showed a significant increase in the incidence of VAP (22% - p = 0.003) and Re-IoT (21.9% - p = 0.048). Thus demonstrating in the sample, which HMV + VB is more effective as the amount of secretion aspirated and has a protective effect, along with the VB, the incidence of VAP and Re-IoT.

Patients who require mechanical ventilation (MV) are at risk for developing ventilator associated pneumonia (VAP). Nurses’ adherence to sedation vacations (SVs) has a direct impact on the development of VAP, because SVs have been shown to reduce patients’ average duration of MV and length of stay (LOS) in the intensive care unit (ICU). The purposes of this study guided by Donabedian’s (1966) model were to quantify nurses’ level of adherence to SVs, in relation to the health outcomes of critically ill patients, and identify the barriers and facilitators to performing SVs. A correlational design was used. The design included three components: abstraction of patient data from the electronic medical record (EMR) (n=79 with VAP and n=79 without VAP), administration of surveys to ICU nurses (N =34), and vignettes related to SVs. Analyses included descriptive statistics, t-tests, correlations, and analyses of covariance. Most nurses held a Bachelors degree (70.6%), had < 9 years of ICU experience (52.9%), worked in a medical ICU (47.1%), and reported high confidence in managing SVs (M =8.88, SD =1.25). The majority of patients (N =158) were Black (58.2%), males (56.3%), and on average middle-aged (M =61.5, SD =14.91), with a long ICU LOS (M =15.5, SD =11.84), extended duration of MV (M =9.5, SD =8.47), and high acuity (APACHE III) (M =70.2, SD =25.42). The nurses’ education, advanced certification, and ICU experience were not associated with the appropriate implementation of SVs in the vignettes. On average nurses’ had low scores on the vignettes (M =6.97, SD =2.21; possible range =0-14). The adherence rate of nurses’ implementation of SVs, determined using EMR data, was also low (M =24%; SD =23%). There were higher rates of SV adherence in patients without VAP (p (p < .01), and a duration of MV < 6 days (p =.04). These findings indicate that even with established protocols, nurses may not consistently implement the evidenced-based interventions that have been shown to prevent nosocomial infections. Future research is needed to improve nursing practice and the quality of care in this patient population.