Therapies In Critical Care Research Articles

Insights from CTTACC: immune system reset by cellular therapies for chronic illness after trauma, infection, and burn

Background AimsIn this paper, we present a review of several selected talks presented at the CTTACC conference (Cellular Therapies in Trauma and Critical Care) held in Scottsdale, AZ in May 2023. This conference review highlights the potential for cellular therapies to “reset” the dysregulated immune response and restore physiologic functions to normal. Improvements in medical care systems and technology have increasingly saved lives after major traumatic events. However, many of these patients have complicated post-traumatic sequelae, ranging from short-term multi-organ failure to chronic critical illness. Methods/ResultsPatients with chronic critical illness have been found to have dysregulated immune responses. These abnormal and harmful immune responses persist for years after the initial insult and can potentially be mitigated by treatment with cellular therapies. ConclusionsThe sessions emphasized the need for more research and clinical trials with cellular therapies for the treatment of a multitude of chronic illnesses: post-trauma, radiation injury, COVID-19, burns, traumatic brain injury (TBI) and other chronic infections.

Implementing integrative therapies in adult critical care: Barriers and strategies

BackgroundCritically ill patients experience intense physical and psychological stressors in the intensive care unit (ICU). More than half of ICU survivors report overwhelming mental health symptoms after ICU discharge, such as post-traumatic stress symptoms, anxiety, and depression. Relaxation-inducing integrative therapies such as guided imagery, massage, therapeutic touch, music therapy, and spirituality-based healing practices have the potential to promote comfort and relaxation and improve patient outcomes. ObjectivesThe aim of this study was to explore the attitudes of healthcare professionals towards the implementation of relaxation-inducing integrative therapies in critical care, barriers to implementation, and potential strategies to overcome them. MethodsWe conducted seven focus group interviews with 23 critical care clinicians (70% nurses, 17% allied health professionals, 13% physicians). Interviews were audiotaped and transcribed verbatim. Data were thematically analysed using an inductive content analysis approach. FindingsResults reveal a constant interplay between mostly positive personal attitudes towards implementation of integrative therapies and the perceived culture and priorities of the unit. The main benefits for critically ill patients as perceived by participants were promotion of comfort, sleep, and coping, increase of trust, and decrease of pain and stress. As for barriers, dominant themes were a perceived lack of evidence, cost, and time constraints and the fear of loss of professional credibility. Participants related nurses’ education and training, family involvement, and leadership were seen as main strategies for implementation. ConclusionsThe dominant ICU culture needs to be considered when implementing integrative therapies. Education, access to evidence, and role modelling are proposed as means to shift the ICU culture towards utilisation of integrative therapies in critical care.

Nebuliser therapy in critical care: The past, present and future

Nebulisers are devices that reduce a body of liquid into a fine aerosol suitable for inhalation. Utilising the efficiency of pulmonary drug absorption, they offer a safe and powerful modality for local and systemic drug delivery in the treatment of critical illness. In comparison to conventional jet (JN) and ultrasonic nebulisers (USN), the advent of vibrating mesh nebulisers (VMN) has significantly improved the therapeutic potential of modern devices. This review article aims to summarise the history and evolution of nebulisers from first inception through to the modern vibrating mesh technology. It provides an overview on the basic science of nebulisation and pulmonary drug delivery, and the current use of nebulised therapies in critical care.

Renal replacement and extracorporeal therapies in critical care: current and future directions

There are a wide number of indications for extracorporeal therapies in the critical care environment. A common indication seen by the acute physician is continuous renal replacement therapy (CRRT) in a proportion of patients with acute kidney injury. It is therefore important that acute physicians have a sound understanding of the principles of CRRT in the acutely unwell patient. This review will outline the indications for its use, commonly used methods and anticoagulation considerations. It will discuss when to start and stop CRRT as well as describing potential treatment complications. This review will also discuss the role of therapeutic plasma exchange in critical care and novel extracorporeal therapies including blood purification in sepsis and carbon dioxide removal in acute respiratory distress syndrome and acute exacerbations of obstructive lung disease. Extracorporeal membrane oxygenation is outside of the scope of this article.

Factors Influencing the Implementation of Prone Positioning during the COVID-19 Pandemic: A Qualitative Study.

Rationale: The adoption of prone positioning for patients with acute respiratory distress syndrome (ARDS) has historically been poor. However, in mechanically ventilated patients with coronavirus disease (COVID-19) ARDS, proning has increased. Understanding the factors influencing this change is important for further expanding and sustaining the use of prone positioning in appropriate clinical settings. Objectives: To characterize factors influencing the implementation of prone positioning in mechanically ventilated patients with COVID-19 ARDS. Methods: We conducted a qualitative study using semistructured interviews with 40 intensive care unit (ICU) team members (physicians, nurses, advanced practice providers, respiratory therapists, and physical therapists) working at two academic hospitals. We used the Consolidated Framework for Implementation Research, a widely used implementation science framework outlining important features of implementation, to structure the interview guide and thematic analysis of interviews. Results: ICU clinicians reported that during the COVID-19 pandemic, proning was viewed as standard early therapy for COVID-19 ARDS rather than salvage therapy for refractory hypoxemia. By caring for large volumes of proned patients, clinicians gained increased comfort with proning and now view proning as a low-risk, high-benefit intervention. Within ICUs, adequate numbers of trained staff members, increased team agreement around proning, and the availability of specific equipment (e.g., to limit pressure injuries) facilitated greater proning use. Hospital-level supports included proning teams, centralized educational resources specific to the management of COVID-19 (including a recommendation for prone positioning), and an electronic medical record proning order. Important implementation processes included informal dissemination of best practices through on-the-job learning and team interactions during routine bedside care. Conclusions: The implementation of prone positioning for COVID-19 ARDS took place in the context of evolving clinician viewpoints and ICU team cultures. Proning was facilitated by hospital support and buy-in and leadership from bedside clinicians. The successful implementation of prone positioning during the COVID-19 pandemic may serve as a model for the implementation of other evidence-based therapies in critical care.

Cell therapies for trauma and critical care medicine: critical issues in translation for cellular and novel therapies in trauma and critical care.

Cell therapies for trauma and critical care medicine: critical issues in translation for cellular and novel therapies in trauma and critical care.

Adjuvant therapies in critical care: music therapy.

Adjuvant therapies in critical care: music therapy.

Adjuvant therapies in critical care: steroids to treat infectious diseases

Adjuvant therapies in critical care: steroids to treat infectious diseases

Adjuvant therapies in critical care: steroids in community-acquired pneumonia.

Severe community-acquired pneumonia (CAP) is present in up to 19% of hospitalized patients with CAP, and still carries a high morbidity and mortality. A French multicentre study of severe pneumococcal CAP admitted to intensive care units (ICU) reported an overall mortality rate of 29%1. The high mortality of severe CAP occurs despite the fact that the majority of patients receive an early and adequate antibiotic treatment. This is probably due, in part, to an imbalanced and disproportionate local and systemic inflammatory response that contributes to impairment of gas exchange, sepsis and end-organ dysfunction.

Cellular Therapies in Trauma and Critical Care Medicine: Forging New Frontiers.

ABSTRACTTrauma is a leading cause of death in both military and civilian populations worldwide. Although medical advances have improved the overall morbidity and mortality often associated with trauma, additional research and innovative advancements in therapeutic interventions are needed to optimize patient outcomes. Cell-based therapies present a novel opportunity to improve trauma and critical care at both the acute and chronic phases that often follow injury. Although this field is still in its infancy, animal and human studies suggest that stem cells may hold great promise for the treatment of brain and spinal cord injuries, organ injuries, and extremity injuries such as those caused by orthopedic trauma, burns, and critical limb ischemia. However, barriers in the translation of cell therapies that include regulatory obstacles, challenges in manufacturing and clinical trial design, and a lack of funding are critical areas in need of development. In 2015, the Department of Defense Combat Casualty Care Research Program held a joint military–civilian meeting as part of its effort to inform the research community about this field and allow for effective planning and programmatic decisions regarding research and development. The objective of this article is to provide a “state of the science” review regarding cellular therapies in trauma and critical care, and to provide a foundation from which the potential of this emerging field can be harnessed to mitigate outcomes in critically ill trauma patients.

Risk Factors Associated With Iatrogenic Opioid and Benzodiazepine Withdrawal in Critically Ill Pediatric Patients

Analgesia and sedation are common therapies in pediatric critical care, and rapid titration of these medications is associated with iatrogenic withdrawal syndrome. We performed a systematic review of the literature to identify all common and salient risk factors associated with iatrogenic withdrawal syndrome and build a conceptual model of iatrogenic withdrawal syndrome risk in critically ill pediatric patients. Multiple databases, including PubMed/Medline, EMBASE, CINAHL, and the Cochrane Central Registry of Clinical Trials, were searched using relevant terms from January 1, 1980, to August 1, 2014. Articles were included if they were published in English and discussed iatrogenic withdrawal syndrome following either opioid or benzodiazepine therapy in children in acute or intensive care settings. Articles were excluded if subjects were neonates born to opioid- or benzodiazepine-dependent mothers, children diagnosed as substance abusers, or subjects with cancer-related pain; if data about opioid or benzodiazepine treatment were not specified; or if primary data were not reported. In total, 1,395 articles were evaluated, 33 of which met the inclusion criteria. To facilitate analysis, all opioid and/or benzodiazepine doses were converted to morphine or midazolam equivalents, respectively. A table of evidence was developed for qualitative analysis of common themes, providing a framework for the construction of a conceptual model. The strongest risk factors associated with iatrogenic withdrawal syndrome include duration of therapy and cumulative dose. Additionally, evidence exists linking patient, process, and system factors in the development of iatrogenic withdrawal syndrome. Most articles were prospective observational or interventional studies. Given the state of existing evidence, well-designed prospective studies are required to better characterize iatrogenic withdrawal syndrome in critically ill pediatric patients. This review provides data to support the construction of a conceptual model of iatrogenic withdrawal syndrome risk that, if supported, could be useful in guiding future research.

Bench-to-bedside review: Erythropoietin and its derivatives as therapies in critical care

Erythropoietin (EPO) is known to have numerous biological functions. Its primary function in the body is to increase red blood cell numbers by way of preventing the apoptosis of erythroid progenitor cells via the homodimeric EPO receptor. The discovery that the local production of EPO within the brain in response to hypoxia or ischemia protects neurons against injury via an anti-apoptotic effect formed the basis of the hypothesis that the local generation of EPO limits the extent of injury. Although the hypothesis proved to be true in pre-clinical models of ischemia/reperfusion injury and inflammation, the randomized, controlled clinical trials that followed demonstrated serious adverse events of EPO due to activation of the hematopoietic system. Consequently, derivatives of EPO that lacked erythropoietic activity were discovered to reduce injury in many pre-clinical models associated with ischemia and inflammation. Unfortunately, there are no published clinical trials to determine the efficacy of non-erythropoietic derivatives of EPO in humans.

Bench-to-bedside review: Vasopressin in the management of septic shock

This review of vasopressin in septic shock differs from previous reviews by providing more information on the physiology and pathophysiology of vasopressin and vasopressin receptors, particularly because of recent interest in more specific AVPR1a agonists and new information from the Vasopressin and Septic Shock Trial (VASST), a randomized trial of vasopressin versus norepinephrine in septic shock. Relevant literature regarding vasopressin and other AVPR1a agonists was reviewed and synthesized. Vasopressin, a key stress hormone in response to hypotension, stimulates a family of receptors: AVPR1a, AVPR1b, AVPR2, oxytocin receptors and purinergic receptors. Rationales for use of vasopressin in septic shock are as follows: first, a deficiency of vasopressin in septic shock; second, low-dose vasopressin infusion improves blood pressure, decreases requirements for norepinephrine and improves renal function; and third, a recent randomized, controlled, concealed trial of vasopressin versus norepinephrine (VASST) suggests low-dose vasopressin may decrease mortality of less severe septic shock. Previous clinical studies of vasopressin in septic shock were small or not controlled. There was no difference in 28-day mortality between vasopressin-treated versus norepinephrine-treated patients (35% versus 39%, respectively) in VASST. There was potential benefit in the prospectively defined stratum of patients with less severe septic shock (5 to 14 μg/minute norepinephrine at randomization): vasopressin may have lowered mortality compared with norepinephrine (26% versus 36%, respectively, P = 0.04 within stratum). The result was robust: vasopressin also decreased mortality (compared with norepinephrine) if less severe septic shock was defined by the lowest quartile of arterial lactate or by use of one (versus more than one) vasopressor at baseline. Other investigators found greater hemodynamic effects of higher dose of vasopressin (0.06 units/minute) but also unique adverse effects (elevated liver enzymes and serum bilirubin). Use of higher dose vasopressin requires further evaluation of efficacy and safety. There are very few studies of interactions of therapies in critical care - or septic shock - and effects on mortality. Therefore, the interaction of vasopressin infusion, corticosteroid treatment and mortality of septic shock was evaluated in VASST. Low-dose vasopressin infusion plus corticosteroids significantly decreased 28-day mortality compared with corticosteroids plus norepinephrine (44% versus 35%, respectively, P = 0.03; P = 0.008 interaction statistic). Prospective randomized controlled trials would be necessary to confirm this interesting interaction. In conclusion, low-dose vasopressin may be effective in patients who have less severe septic shock already receiving norepinephrine (such as patients with modest norepinephrine infusion (5 to 15 μg/minute) or low serum lactate levels). The interaction of vasopressin infusion and corticosteroid treatment in septic shock requires further study.

Disseminating clinical trial results in critical care

Efficient translation of clinical evidence into clinical practice is among the greatest challenges to evidence-based medicine. The field of knowledge transfer seeks to understand the barriers to evidence uptake and develop new methods to effectively disseminate clinical trial results. Traditionally, barriers to evidence-based practice are categorized into those of knowledge, attitudes, and behavior. Efforts to improve translation of evidence into practice should uncover and address each of these barriers and be customized to the specific intervention. To help aid knowledge transfer, interventions in clinical trials should be as simple as possible and answer questions important to actual caregivers. Potentially innovative methods for improving knowledge transfer include expanding community research networks, clinical registries to monitor evidence uptake, and community-based participatory research. It is essential that investigators conducting clinical trials prioritize knowledge transfer to ensure that new therapies in critical care are actually reaching the critically ill.

Renal replacement therapies in critical care

Renal replacement therapies in critical care

Nurse attitudes towards the use of complementary and alternative therapies in critical care

Background There is increasing demand for complementary/alternative therapies (CAT) in critical care, however, critical care nurses’ perspectives regarding CAT are unknown. Objectives This study was conducted to determine critical care nurses’ knowledge, attitudes, and use of CAT. Sample/setting A total of 348 critical care registered nurses working at least 40% in medical, surgical, cardiac, neurological, and pediatric ICUs at 2 tertiary-level hospitals in a large Midwestern city were surveyed. One hospital is a 926-bed private, urban hospital and the second is an 1868-bed academic-affiliated medical center. Methods A survey was distributed to all critical care nurses described above. Results The level of knowledge reported by 138 nurse respondents was greatest for diet, exercise, massage, prayer, and music therapy. Use of therapies was related to knowledge and training and consistent with beliefs of legitimacy and perceptions of beneficial effects. Despite barriers including lack of knowledge, time, and training, 88% of respondents were open or eager to use CAT, and 60% reported moderate or greater desire to use CAT. Conclusions Critical care nurses are open to CAT use and many use them in their own practice. Because use was associated with knowledge, recommendations for future research include increasing the scientific base and enhancing knowledge to promote evidence-based incorporation of CAT in practice.

Evaluating the economics of novel therapies in critical care

Evaluating the economics of novel therapies in critical care

Translating research evidence into clinical practice: new challenges for critical care

High quality research evidence is now available to guide and shape the practice of critical care. As the generation of such evidence increases, the challenge facing critical care medicine will be translation of this evidence into measurable improvement in patient outcome. Significant barriers to this process of translation exist that will require substantial effort and resources to overcome. We briefly review the nature of translational barriers to incorporation of research evidence into clinical practice and the conventional approach to surmounting these barriers, and provide examples of barriers and potential solutions to emerging therapies in critical care.