Extra-corporeal membrane oxygenation (ECMO) is a life-saving procedure for patients in respiratory or cardiac distress. Prior studies have demonstrated several known risks to the procedure, such as hypoxia, stroke, and other neurological complications (Cheng et al., 2014) that can lead to temporary or permanent deficits in motor abilities, developmental trajectory, academic abilities, and cognition (Glass et al., 1995). Although several studies have investigated morbidity and mortality rates of pediatric ECMO patients, few have looked at cognitive deficits, and even fewer at magnetic resonance imaging in relation to neuropsychological outcome and behavioral, emotional, or social functioning. The aims of this study were to investigate cognitive ability and behavioral functioning in a group of ECMO-treated patients compared to a normative sample, and to examine brain morphometry in hippocampal regions as they relate to cognitive outcome. Participants for this study were recruited from Primary Children's Hospital in Salt Lake City, UT. The total number of participants recruited was 8 (63% female; M age at testing = 16.75, SD = 4.5), and all participants were at least 1 year post-ECMO procedure (M=5.6 years; SD=2.1) for acute respiratory or cardiac illness. Neuropsychological testing was completed using the NIH Toolbox Cognition Battery. Scores were compared to normative data for age to investigate potential impairment in multiple cognitive domains. Each participant and the parent or guardian of minor participants completed brief questionnaires measuring executive functioning, behavior, and social skills, namely The Behavior Rating Inventory of Executive Functioning, The Behavioral Assessment System for Children, Second Edition, and the Social Skills Improvement System Rating Scales. Six of the participants also underwent MR imaging to obtain measures of cortical thickness in the frontal areas of the brain, as well as hippocampal and total intracranial volume. Performance results on the NIH Toolbox Cognition Battery was impaired in over half of the tested individuals who underwent ECMO as children. Attention, executive function, processing speed, and visual memory were well below the expected range for age in the majority of participants. Crystallized intelligence tasks, such as vocabulary, were in the average to above average range for most participants, likely indicating normal baseline functioning. Self- and informant report revealed variable results across participants, with various behavioral, emotional, and social difficulties reported in the group. Bilateral hippocampal volume was positively correlated with scores on tasks of episodic and working memory, though further study with a larger sample and control group is warranted. Preliminary MRI data for cortical thickness and volume of frontal regions are presented. Interpretation of results, limitations, and future directions are discussed.

L’arrêt cardiaque (AC) extrahospitalier est un problème majeur de santé publique, malgré la mise en place d’une véritable « chaine de survie ». Les durées de réanimation sont souvent prolongées et aboutissent à des séquelles irréversibles avec un assombrissement dramatique du pronostic. Dans de nombreuses situations, l’AC ne parvient pas à être réanimé avec les soins courants, laissant apparaître un AC « réfractaire » qui nécessite une prise en charge thérapeutique avancée. L’objectif général de ce travail de thèse était d’évaluer de nouvelles approches expérimentales pour la prise en charge de l’AC réfractaire. Nous avons étudié deux stratégies expérimentales chez le porc, consistant à induire une hypothermie ultra-rapide par ventilation liquide ou à mettre en place une assistance circulatoire au cours d’un AC d’origine ischémique.Dans un premier travail, nous avons ainsi évalué la faisabilité d’une hypothermie thérapeutique ultra-rapide par ventilation liquidienne totale (VLT) chez le porc. Cette approche consiste à instiller des perfluorocarbones dans le poumon de façon à induire un refroidissement ultra-rapide. Le poumon est ainsi utilisé comme bio-échangeur thermique, tout en maintenant des échanges gazeux normaux. Dans des travaux préliminaires, le laboratoire a montré que la VLT permettait de réduire la température sanguine jusqu’à 32°C en moins de 10 minutes chez le lapin. Le but de notre étude était de déterminer si la VLT pouvait aussi permettre un refroidissement ultra-rapide chez le porc. L'effet de la VLT a ainsi été évalué dans un premier temps à cœur battant, puis à cœur arrêté sur un modèle d’arrêt cardiaque réfractaire bénéficiant d’une réanimation cardio-pulmonaire prolongée. Dans les conditions physiologiques « à cœur battant », la température de 34°C était atteinte en moins de 10 minutes dans tout l'organisme. Lors de la réanimation prolongée d’un AC réfractaire, le refroidissement corporel était également obtenu rapidement, en moins de 25 minutes, quel que soit le site de mesure de la température. La VLT n’altérait aucunement la qualité du massage cardiaque externe, suggérant un intérêt pour cette approche dans l’induction d‘une hypothermie intra-AC, dans une perspective d’augmentation de l’efficacité des défibrillations ou de préservation d’organe.Dans un deuxième travail, nous nous sommes intéressés à l’AC réfractaire compliquant un syndrome coronaire aigu, traité par assistance circulatoire extracorporelle. Notre but était d’évaluer l'importance de la revascularisation coronaire précoce dans cette situation chez le porc, c’est-à-dire son impact sur le statut hémodynamique et les chances de réanimation. Après anesthésie et instrumentation, les animaux ont ainsi été soumis à une occlusion coronaire, suivie d’un AC par fibrillation ventriculaire non traitée pendant 5 minutes. Ils ont ensuite bénéficié d’une réanimation cardio-pulmonaire de base puis d’une assistance circulatoire extracorporelle. Nous avons comparé les effets d’une revascularisation précoce à ceux d’une revascularisation tardive, c’est-à-dire d’une reperfusion 20 ou 120 min après le début de l'assistance circulatoire. La revascularisation coronaire précoce augmentait significativement les chances de reprise d’activité cardiaque spontanée, limitait l’état de choc, améliorait la perfusion cérébrale et limitait la taille d’infarctus. Cela montre bien l’importance d’une prise en charge rapide du syndrome coronarien en cas d’AC de cause cardiaque présumée, y compris dans une situation d’assistance circulatoire extracorporelle.En conclusion, nous avons montré que la VLT permettait d’induire un refroidissement ultra-rapide dans l’ensemble de l’organisme, tant à cœur battant que pendant une réanimation prolongée. Par ailleurs, la revascularisation précoce d’un AC réfractaire ischémique traité par assistance circulatoire extracorporelle permettait d’améliorer globalement les chances de réanimation et le statut hémodynamique. / Out of hospital cardiac arrest (CA) is a major public health issue, despite the implementation of a “chain of survival”. Resuscitation durations are often extended with irreversible organ damage and poor outcome. Frequently, conventional care does not allow the return of spontaneous circulation, leading to a refractory CA, with the need for advanced therapeutic care. The general objective of this work was to evaluate new therapeutic strategies in the management of refractory cardiac arrest. We studied two experimental strategies in swine, involving ultrafast cooling with total liquid ventilation or extracorporeal cardiopulmonary resuscitation in a CA of ischemic origin.As a first step, we evaluated the feasibility of ultra-fast therapeutic hypothermia using total liquid ventilation (TLV) in swine. This approach involves perfluorocarbon instillation in the lungs to induce ultra-fast cooling. The lungs are thus used as a heat exchanger, while maintaining normal gas exchanges. In previous studies, the laboratory has shown that TLV could reduce blood temperature to 32°C in less than 10 minutes in rabbits. The objective of this study was to determine if TLV could lead to ultra-fast cooling in swine. We first studied the cooling capacity of hypothermic TLV in beating heart pigs, and then during ventricular fibrillation with prolonged chest compressions. In physiological conditions, in “beating heart” animals, the target temperature of 34°C was obtained in less than 10 min in the whole body. In prolonged resuscitation of refractory CA, whole body cooling was also rapidly obtained, within less than 25 min. TLV did not alter the hemodynamic effect of cardiac compressions, suggesting further use of this “intra-resuscitation” cooling in order to increase chances of defibrillation or for organ preservation for the purpose of organ donation.As a second step, we addressed the subject of ischemic refractory CA treated by extracorporeal cardiopulmonary resuscitation (ECPR). Our objective was to evaluate the importance of early coronary reperfusion in this situation, i.e., it’s impact on hemodynamic status and chances of defibrillation. After anesthesia and surgical preparation, animals were submitted to a coronaryocclusion followed by 5 min of CA by ventricular fibrillation. Conventional cardiopulmonary resuscitation was then initiated and followed by extracorporeal cardiopulmonary resuscitation.We compared the effect of early versus late reperfusion, i.e., reperfusion after 20 or 120 min of ECPR. Early reperfusion significantly increased chances of return to spontaneous circulation with limited shock status, increased cerebral perfusion and decreased infarct size. This confirms the need for early treatment of acute coronary syndrome if cardiac cause of CA is suspected, even in the situation of ECPR.In conclusion, we have shown that TLV could provide ultra-fast whole body cooling, both in beating heart swine and during prolonged resuscitation. Secondly, early reperfusion in refractory ischemic CA treated by ECPR globally increases chances of return to spontaneous circulation and improves hemodynamic status.

The 2009 Influenza A (H1N1) virus quickly became a pandemic and a threat to the health of many across the globe. H1N1 was able to preferentially bind to pneumocytes in the lower lung, resulting in atelectasis, surfactant disruption, and eventual acute respiratory distress syndrome (ARDS). Management of ARDS during this time included non-ventilatory and ventilatory techniques such as conservative fluid management, prone positioning, differing PEEP levels, and Extracorporeal Membrane Oxygenation (ECMO). High cost, unequal global access to ECMO centers, and complication rates present challenges to future ECMO expansion. Despite this, the available information supports the use of ECMO for H1N1-associated ARDS. Future studies and simulations should be conducted to expand the knowledge base on using ECMO as a treatment for pandemic influenza-associated ARDS, with particular attention on bridging gaps in access for the most vulnerable and affected populations.

Extracorporeal membrane oxygenation (ECMO) is a medical treatment that aims to support patients' respiratory and circulatory systems by oxygenation of blood outside of the patient. The therapy exposes blood to an artificial environment, which increases the risk of clot formations in the blood. This thesis proposes a noninvasive method to detect the development of thrombi in the ECMO circuit (which may cause patient complications) by measuring the blood pump motor effect and blood flow. To show the feasibility of this approach, a code that calculates pump efficiency changes due to adjustments of flow resistance shall be written and tested with a mock-up of an extracorporeal life support (ECLS) circuit. Results indicate there exist different flow efficiency relations. Efficiency seems to be influenced by design; certain rotation speeds have higher efficiency than others. As flow increases, so do efficiency (for our values, 3-5 Litres per minute, LPM). For 3 LPM, the highest efficiency was achieved at around 2800 RPM; 4 and 5 LPM start with higher efficiency but decreases as RPM increases. It was concluded that it is possible to differentiate between various flow restrictions using power consumption assessments. Low resistance changes, reduction of cross-section area for flow by 10% on the inlet side, and 16% on the outlet side showed no difference in impeller turning speed nor flow out of the pump. / Extrakorporeal Membranoxygenering (ECMO) är en livräddande behandling för att syresätta patienters blod utanför kroppen vid svår andnings eller cirkulationssvikt. I ECMO-systemet utsätts blodet för en artificiell miljö som medför högre risk för koagulationsaktivering och blodproppsbildning. Detta arbete undersöker möjligheten att icke-invasivt mäta flödesresistanser (som proppar) utifrån att mäta förbrukningseffekten hos den elektriska blodpumpen i ECMO systemet. För att undersöka detta skrivs en kod för att ge en uppskattning av vid varierande flödesrestriktioner uppmätta värden. Dessa värden tas från en befintlig modell på KTH:s Strömningsfysiklaboratorium. Låga flödesrestriktioner påverkar varken flöde, motorrotationshastighet eller motorns effektförbrukning. Detta arbete fann att 10% av slangen till motorn och 16% av slangen från motorn kan vara täckt utan påverkan. Effektiviteten av pumpen varierar beroende på olika variabler. Detta arbete fann att effektiviteten ökar med ökat flöde 3 till 5 liter per minut (LPM). Det verkar även finnas indikationer för att effektiviteten beror på rotationer per minut (RPM), för 3 LPM fanns den högsta effektiviteten kring 2800 RPM, 4 LPM har sin högsta effektivitet vid samma område och 5 LPM har sin högsta effektivitet vid start och avtar därefter. Detta arbete fann att det är möjligt att beräkna flödesrestriktioner utifrån att kontinuerligt notera värdet på en elmätare kopplad till ECMO enheten.

Bakgrund: På ECMO-centrum behandlas patienterna med hjälp av hjärt-lungmaskin. De har ofta multiorgansvikt vilket ställer höga krav på sjuksköterskorna då de ansvarar för patienternas totala omvårdnadsbehov. I och med flytten till NKS förändrades vård- och arbetsmiljön då man gått från öppen vårdmiljö till enskilda vårdrum. Syftet med studien är att beskriva ECMO-sjuksköterskors uppfattningar om hur vård- och arbetsmiljö har påverkats efter flytten till NKS. Metod: Arbetet genomfördes med en kvalitativ metod, med induktiv ansats. För att besvara studiens syfte valde författarna att använda sig av fokusgruppsintervjuer med sjuksköterskor anställda vid ECMO-centrum. Två intervjutillfällen genomfördes under november 2017. Intervjuerna transkriberades ordagrant av båda författarna och analyserades med en kvalitativ innehållsanalys. Resultat: I den nya vård och arbetsmiljön uppfattade sjuksköterskorna att lokalernas utformning utgjorde ett hinder för att bedriva god och säker omvårdnad. Att arbeta i enskilda vårdrum har lett till ökat ensamarbete och möjlighet till rast och kunskapsutbytet har försämrats. En sorg och frustration finns över att inte ha fått ha möjligheten att påverka vård och arbetsmiljö. Slutsats: Vikten av att känna delaktighet och möjligheten att kunna påverka är en förutsättning för att skapa en bra vård- och arbetsmiljö. / Background: At the ECMO Centre patients are treated with a heart-lung machine. Often they suffer from multiple organ failure which places high demands on the nurses as they are responsible for the total nursing care of these patients. With the move to the Nya Karolinska Solna (NKS) the working environment has changed so that all patients are treated in single- patientrooms. The aim of this study is to describe the ECMO nurses perception of how the nursing care and working environment has been affected by the move to NKS. Method: The study was conducted using a qualitative method, with an inductive approach. Focus group interviews were held with nurses employed at the ECMO Centre with the aim of reaching answers in regards to the purpose of the study. Two rounds of interviews were completed in November 2017. The interviews were transcribed word for word by both authors and analysed with a qualitative content analysis. Result: In the new care and working environment, nurses perceived that the design of the premises was a barrier to pursuing good and safe care. Working in single bedrooms has led to increased loneliness and the possibility of taking a break and the exchange of knowledge has deteriorated. There is a sadness and frustration that they didn’t have an opportunity to affect the health and work environment. Conclusion: The importance of feeling participation and the ability to influence is a prerequisite for creating a good health and work environment.

Over 26 million Americans suffer from pulmonary disease, resulting in more than 150,000 deaths annually. Lung transplantation remains the only definitive treatment for many patients, but has meager survival rates and only approximately 1,700 of the 2,200 patients added to the lung transplant wait list each year are transplanted. Extracorporeal gas exchangers have been used as an alternative to mechanical ventilation in acute respiratory failure and as a bridge to transplantation in chronic respiratory failure. Current gas exchangers are limited by their high resistance and low biocompatibility that lead to patient complications and device clot formation. Therefore, there exists a dire need for improved devices that can act as destination therapy. To accomplish the goal of destination therapy, this dissertation discusses three studies that were performed to pave the way. First, I examined clot formation and failure patterns of two common clinical devices (Maquet’s CardioHelp (CH) and Quadrox (Qx)) to further our understanding of their limitations with respect to long-term support. Overall, it was demonstrated that the Qx devices fail earlier and more frequently than CH devices and result in a significantly greater reduction in platelet count, and that a four-inlet approach is beneficial. Next, I determined the optimal sweep gas nitric oxide (NO) concentration that minimizes platelet binding and activation while ensuring that blood methemoglobin (metHb) concentrations increase less than 5%. Miniature artificial lungs were attached to rabbits in a pumped veno-venous configuration and run for 4 h with NO added to the sweep gases in concentrations of 0, 100, 250, and 500 ppm (n=8 ea.). 100 ppm significantly reduced the amount of platelet consumption (p < 0.05), reduced platelet activation as measured by soluble p-selectin (p < 0.05), and had negligible increases in metHb and will thus be used in future experiments. Last, I tested the Pulmonary Assist Device (PAD) which was designed for long term use as a bridge to transplantation and destination therapy. Benchtop experiments were performed that confirmed that it meets our design and performance goals. From here, we are equipped to commence with 30-day PAD testing in sheep.

Introduction: This dissertation thesis aims to describe microcirculatory changes in cardiac arrest setting and to assess the impact of circulatory supports (i.e. mechanical chest compressions and extracorporeal membrane oxygenation (ECMO)) on tissue microcirculation. Methods and results: Two separate studies were designed. Microcirculation was monitored sublingually by a recent Sidestream Dark Field (SDF) technique and its parameters were evaluated offline, separately for small (of diameter ≤ 20µm) and other vessels. In order to monitor microcirculation during cardiac arrest (CA) and resuscitation (CPR) an experimental pig model was used; eighteen pigs were commenced to 3 minutes of untreated CA and subsequent 5 minutes of mechanical CPR. During CA the microcirculatory parameters deteriorated, in CPR they improved and reached 59 - 85 % of the prearrest values. The microcirculatory variables correlated neither to parameters of systemic circulation (mean arterial blood pressure and carotid blood flow) nor to lactate. In the second, clinical, study the sublingual microcirculation was monitored 29 (± 17) hours after the CA onset in 15 patients, who were after unsuccessful conventional CPR rescued by ECMO. In comparison to healthy (sex and age matched) volunteers, the patients showed mild but...

Infectious diseases are the worldwide leading cause of morbidity and mortality. Sepsis is the major cause of death in infectious diseases. It is one of the most serious and also one of the most difficult treatable conditions of contemporary medicine. Sepsis is the main cause of death in intensive care units. Causal therapy of sepsis does not yet exist. With a far better understanding of patho/physiological mechanism of sepsis, it is possible to model new preclinical experiments to verify the efficiency and security of new therapeutic procedures. Large animal experiments in progressive sepsis, with the use of domestic porcine, play a vital role. Long-standing experience with this model and similarity to human facilitate the realization of more complex experiments with potential for the relevant translation of results into the subsequent clinical studies on human subjects. The objective of this doctoral dissertation was to assess on the clinically relevant model: 1) the efficiency and security of extracorporeal membrane oxygenation in the event of vasoplegic septic shock; and 2) the benefit of two innovative therapeutic approaches to treatment of sepsis: a) the intravenous administration of mesenchymal stem cells; and b) the activation of the neuro-inflammatory reflex through the vagus nerve stimulation.

The incidence of acute myocardial infarction is still high. One of the methods of reperfusion therapy is the cardiac surgery by coronary artery bypass graft, which may be postoperatively complicated by the development of postcardiotomy cardiogenic shock with the urgency of the venoarterial extracorporeal membrane oxygenation (V-A ECMO). The quality of very specialized and complex care for these long-term hospitalized patients depends on understanding their needs and ways of saturation. The aim of this study is to present these needs from the perspective of the patient and their family. Research questions ain to identify the main aspect of recovery, the factors negatively affecting the mental state of patients, the ways to help them by healthcare professionals and family, how can healthcare professionals help the family and how this experience has affected both the family and the patient. The research is carried out using a qualitative method of semistructured interview with six respondents with this type of anamnesis, who were hospitalized between 2015 and 2021 in the ICU of cardiac surgery department, and three of their relatives. According to the study's findings the main aspect of recovery is the patient's mental well-being. The dependence on help of others, muscle weakness and loss of intimacy...

Introduction: Extracorporeal membrane oxygenation (ECMO) is a complex tool used in times of cardio and pulmonary failures. It began as a tool used in neonates and gradually evolved to adult use in 2003 and increased in popularity during the time of the H1N1 influenza. As this procedure is risky, it is important to assure all factors are optimized to ensure successful patient outcomes. The time of day a patient is placed on ECMO may play a significance in determining their survival after ECMO. Methods: The study was performed as a single-center, retrospective chart review and database analysis of prospectively collected data from February 7th, 2009 until December 31st, 2021. Data was analyzed using Excel and R studio and logistic regressions and odds ratios were calculated assessing time of day a patient was placed on ECMO to survival to ECMO decannulation, survival to discharge, and survival to one year. Results: There was no statistically significant correlation for time of day and survival outcomes of ECMO except for survival to discharge. Survival to discharge had a positive odds ratio associated with day hours with a statistically significant p value. Discussion: There is no immediate explanation why survival to discharge had a statistically significant correlation with time of day and survival to ECMO decannulation did not. It is possible that the study needs to be repeated with a greater sample size to produce statistically significant results. It is possible that there is a correlation with time of day and ECMO outcomes but the sample size is not large enough to convey that.