Education and Training and Use of Sepsis Six - Assignment Example

A literature review on nurse’s knowledge, understanding, education and training and use of Sepsis Six Introduction Globally within hospital environments around the world, one of the leading causes of death amongst ill and critically ill patients is sepsis and septic shock (Daniels et al, 2011). Sepsis is primarily a consequence of the patient’s immune system responding in an aggressive hyperactive manner in an attempt to respond to infection to limit cellular damage caused by pathological insult (Rittirsch et al,2008). Sepsis is responsible for in excess of 38,000 deaths on an annual basis in the UK alone (Daniels 2011), of these, 5000 cases identified in Wales have resulted in more than 1800 fatalities (Robinson 2013). I have used the Sepsis Screening Tool Questionnaire as a resource. This is an easy tool to help care givers notice symptoms and understand a patient’s vulnerability towards sepsis (Appendix I).Furthermore, The resource always spells out the duties that a nurse needs to follow when sepsis is identifies. I have selected this topic primarily because sepsis, even today, is one of the major causes of death and I feel that nurses can make a big difference in decreasing the current mortality and morbidity rates caused by sepsis in critically ill patients. One of the challenges of treating sepsis pertains to its ability to avoid early accurate recognition. It’s diagnosis by Health Care Professionals (HPC’s) is time sensitive in terms of implementation of treatment. Delay has the consequence of infection spread with cell destruction that results in poorer outcomes and increased patient mortality (Byrnes, 2012). As Sepsis has become a global epidemic, many experts and clinicians have collaborated to establish guidance under the Surviving Sepsis Campaign (2002) in order to help support and educate all healthcare professionals to identify and manage this life threatening condition at its earliest clinical indicator, in a uniform structured approach. Like stroke or MI, sepsis is a time sensitive medical emergency which, if left untreated results in an increase of almost 8% mortality hourly for delay in treatment (Daniels, 2011). Consequently, the introduction of Care Bundles have shown efficacy in addressing the dilemma of patient mortality in relation to sepsis, with several studies presenting favourable outcomes in mortality figures following the successful intervention of the Sepsis Six Bundle and Resuscitation Bundle (Levy et al, 2010). HPC’s, in particular nurses, play a pivotal role in early recognition of the clinical indicators of sepsis, its management, and the necessity of early and significantly the appropriate interventions needed for patients. For that very reason, it is vital that nurses receive education and training in order to care for them suitably in the clinical environment, and fulfil their professional and legal obligations (Nursing and Midwifery Council, NMC, 2008). This assignment will explore nurses’s knowledge, understanding, education and training and use of Sepsis Six. Literature Search Strategy Conducting a survey of the most relevant evidence based literature to fulfil the aim of this assignment was instrumental. Online databases such as PubMed, CINAHL and NCBI were primarily used to obtain scholarly and per reviewed articles. Important key words that were used during the search includes- “sepsis”, “Sepsis Six Bundle”, “Nursing+ sepsis”, “Sepsis Campaign”, “sepsis+ infection”, “catheters”, “education+ clinical settings” and so on. The search produced a number of published articles, which were read to determine their relevancy. Backward and forward chaining has been used, as well. After the first phase of reading, 40 articles were deemed relevant to the aim of the assignment and out of the 40, 35 have been finally included. Sepsis Sepsis is part of the cycle of physiological retort of Systemic Inflammatory Response Syndrome (SIRS). The body’s immune system begins to react in an antagonistic unsympathetic destructive way to infective invaders and micro- organisms (Cohen, 2002).The body’s normal reaction is one of containment, once immunity is compromised(Rittirsch et al,2008). This is often the case in critically ill patients who may also have other significant co-morbidities as a result physiologically they lack the ability to prevent inflection spread. This leads to indiscriminate cell destruction, and attack of other major organs around the body (Horner et al, 2004). Sepsis is a master of disguise, producing many physiological disparities; these include: hyperthermia or hypothermia; tachycardia > 90bpm; warm or cold extremities; confusion and unexplained rashes (Bone et al, 1989). Figure 1: Relation between Infection, SIRS, sepsis, Severe sepsis and Septic shock (Bone et al, 1992). Septic shock, the extreme and often fatal end play of sepsis, if left untreated, leaves the body unresponsive to resuscitation, producing, hypotension, oliguria,acidosis and eventually death. SIRS is a result of infection, which upon confirmed infectious process leads to Sepsis. Sepsis causes multiple organ failure and results in severe Sepsis and Septic Shock. Figure 2: Sepsis Continuum (Bone et al, 1992). Pathophysiology of Sepsis In a normal person, inflammatory reaction in the body is a mechanism to fight microbial invasion without damage to the body’s own tissues or cells. However, in extreme cases such as sepsis the inflammation tends to become more intensive and aggressive in nature. The onset of sepsis causes inflammatory response all over the body and initiates several pathophysiological changes. As Sepsis evolves, changes are noticed in the body’s coagulation system and the cells involved in the coagulation system. Patients who develop sepsis may develop disseminated intravascular coagulation (DIC) and the normal clotting time also increases (Remick, 2007). Altered function or total inactivation of cellular functions is also observed in patients who develop sepsis. According to a study conducted by Hotchkiss et al (1999), cell death of lymphocytes (most important for initiating response against sepsis) is seen to occur in patients with sepsis. Other pathophysiological changes in patients who develop sepsis include alterations in the metabolic pathways as well. Multiple organ failure (MOF) can occur if infection is not recognised early enough and allowed to progress to sepsis. It primarily refers to alteration in the mode of functioning of the different organs of the body and loss of the state of homeostasis. Some of the signs of organ dysfunction includes severe effect on the central nervous system with altered mental functioning, negative effect on respiratory, renal and cardiovascular systems along with rapid declination in blood platelet count (McClelland and Moxon, 2014). Causes of Sepsis Sepsis has a wide number of causes and maybe triggered by infection in any part of the body ranging from skin, lungs, and urinary tract to abdominal and pelvis. Onset of sepsis may occur in anyone, however, some people are much more likely to develop sepsis than others. People with depressed immunity (e.g. HIV patients, cancer patients), newborns, critically ill patients, people who have undergone recent invasive medical procedures and the elderly population are more vulnerable to development of sepsis than others. Factors responsible for Sepsis in Critically ill patients Critically ill patients are perhaps most vulnerable to the development of sepsis in their body given to their vulnerability to infection. Several studies have shown that development of sepsis was a major cause of death in Intensive Care Units (ICU) (Kaukonen et al, 2014). Biomarkers are perhaps the best way to understand or recognise the development of sepsis in patients. This is of primarily high importance since delay in recognising the onset of sepsis and initiation of proper management may result in death of the patient. Several researchers have proposed biomarkers such as Procalcitonin, various kinds of interleukins, interferons, andrenomedullin and pro-andrenomedullin etc. (Harbarth et al, 2001; Wu et al, 2009; Guignant et al, 2009). Of all these options Procalcitonin has been most extensively studied and holds more promise in aiding in diagnosing critically ill patients with sepsis. Studies have shown that there is a rapid elevation in the amount of Procalcitonin in the serum in cases of sepsis and organ dysfunction. In fact, the relation between the quantities detected in the serum is directly proportional to the extent of sepsis and organ failure (Kibe et al, 2011). However, in many cases just using one single biomarker for accurate identification of sepsis development may not be useful and hence it is also proposed that a combination of biomarkers maybe used for the same. Gibot et al, (2012) conducted a cohort study on the success of a combination of biomarkers over using a single biomarker within the clinical settings and established that a combination of the PMN CD64 index with other biomarkers such as PCT and sTREM-1 was extremely accurate in identifying the onset of sepsis compared to the practice of using just a single biomarker. Current Nursing Practice The primary aim of nurse’s is to assist patients in overcoming their illnesses with minimum problems both physically and psychologically. Nurses are responsible for the basic surveillance in critically ill patients who run the risk of developing sepsis. Nurses should endeavour to engage in evidence based practice while dealing with patients with sepsis. With the global escalating problem of sepsis, the Surviving Sepsis Campaign (SSC) was initiated under which several evidence based practice methodologies have been introduced and upgraded to ensure that sepsis patients receive proper treatment with the shortest time frame. SSC aims at not only improving patient outcomes but also improving diagnosis and management of the problem as well. The SSC has introduced several bundles, which are utilised by nursing professional to recognise and manage patients who develop sepsis or are likely to develop sepsis. According to a study conducted in the U.S. on critical care nurses, it has been demonstrated that not all guidelines of the SSC are met accurately for improvement of patient outcomes. It was seen that hospitals are quick in their action of ordering blood cultures and administering broad spectrum antibiotics according to the guidelines laid down by the SSC. However, other important points such as initiation of drotrecogin alfa was not fulfilled within the recommended time frame(Durthaler et al, 2009). Therefore, it is obvious that the current nursing practice is based on the guidelines recommended by the SSC. The SSC comprises of three proposed phrases: 1. Implementation of Six point action plan to reduce global mortality as result of sepsis. 2. Creation of more guidelines for management. 3. Translating the guidelines into clinical practices through institutional education and campaigning (SSC guidelines, 2014). The SSC introduced the concept of using bundles to monitor and manage all forms of sepsis. The bundles basically comprises of a number of different therapies which are applied together to obtain optimum result. The application of the bundle of therapies together have proven to be much more effective than applying just one or two of the therapy on individual patients (Khan and Divatia, 2010). The simplicity and the effectiveness of the bundle concept have helped in making it popular and practical (Levy et al, 2004). Potential Barriers Successful implementation of intervention practices is often compromised owing to a number of factors. One of the major problems is staffing numbers. Protocol based sepsis intervention is mostly hampered owing to critical shortage of nurses (Carlbom and Rubenfeld, 2007). This shortage creates an unbalanced nurse to patient ratio such that a single caregiver is assigned the responsibility of many patients at a given time. Proper education, training and hands on experience also add to the implementation barrier. Lack of knowledge about potential gaps in the protocol decreases sepsis care and management as well (Burney et al, 2012). Lack of proper education also devoid the nurses of the basic attitude and behaviour while handling sepsis cases (Burney et al, 2012). In addition to these several other factors such as resource limitation, lack of skill etc act as potential barriers as well. Sepsis Six Bundle The most important thing for nurses to remember while trying to manage sepsis is to get the basics right within the smallest period of time so as to restrain the magnitude of the problem. The Sepsis Six Bundle is a concept that was initiated in 2006 to help combat the growing problem of septic incidences among patients. In fact the sepsis six bundle rapidly gained popularity as a tool to help survive sepsis. The bundle consists of a combination of diagnostic and therapeutic procedures which may be initiated within one hour of detection of sepsis. It includes using a non-Rebreathe mask to deliver oxygen. Patients with sepsis need to be given higher volumes of oxygen to eliminate hypo perfusion. However, while supplying such high levels of oxygen, nurses need to know if the patient has any chronic lung ailments, which may not be able to bear the extra supply of oxygen. The Bundle also requires Taking blood culture of the patient before administering of antibiotics. Collection of blood samples of the patient is deemed necessary since it allows proper identification of the microbes and hence helps in determining the antibiotic, which needs to be administered to the patient to tackle the problem. Cultures also need to be taken from sputum and urine as well. ABHB guidelines need to be adhered to while administering anti-biotics. Nurses need to administer broad-spectrum antibiotics preferably within an hour of diagnosis with sepsis. However, before administration nurses need to know about the allergies of individual patients so as not to add to the complication. The therapy using antibiotics needs to be reviewed on a daily basis to reduce probability of resistance and risk of toxicity (Dellinger et al, 2013). Sepsis Six Bundle calls for resuscitation with fluids depending on patient’s need.Resuscitation using fluids is extremely important since it will help limit the hypotension and also revert the altered cardiac output in the patient. Nurses need to accurately understand and decide the amount of fluid to be supplied. At present it is recommended that sepsis patients who have raised lactate or are suffering from hypotension be given 30ml/kg of crystalloids (Dellinger et al, 2013). Measuring the serum lactate count is also extremely important. Once diagnosed with sepsis calls for immediate count of the blood cells and levels of lactate in the serum. It is to be noted that a high lactate count may point towards a depressed immune functioning and onset of severe sepsis. Furthermore, Use of catheter to monitor hourly urine balance. (See Appendix 1).Catheters need to be inserted to get an accurate estimation of the hourly urinary output and get an accurate account of the circulating fluid and kidney functions. However catheter insertion increases the chances of infection as well (McClelland and Moxon, 2014). Literature Review and Summary NHS England have reported that adoption and proper implementation of the Sepsis Six Bundle lowers the percentage of deaths causes by sepsis by almost 47% (NHS, 2014). It has also been estimated that if the NHS could succeed in properly implementing the Bundle and adhere to the basic needs of the guidance almost 15,000 lives could be saved in the UK alone (NHS, 2014).There have been a number of studies that have been conducted to gain an idea about the prospects of the Sepsis Bundles that have been introduced under the Surviving Sepsis campaign. Daniels et al (2011) conducted an observational cohort study in a 500-bedded general hospital to study the delivery of sepsis interventions and the outcomes of the implementation of the Bundle. The researchers observed the degree of proper and accurate adherence to the basic methodologies described in the bundle and rate of mortality of the patients in 567 patients who had received the Sepsis Six Bundle intervention. The data was analysed and it was seen that 84.6% of the patients who received the intervention achieved the resuscitation bundle, which showed that the patients who received Sepsis Six Bundles were more likely to receive the full bundle over others who did not. The study also suggested an association of the between a reduction in the mortality rate of patients and Sepsis Six Bundle implementation (Daniels et al, 2011).In another similar study Chen et al, (2008?) conducted a prospective clinical study on the impact of interventions with sepsis bundles on the mortality of patients with septic shock. The researchers conducted the study on 100 critically ill patients who developed septic shock. The phases of the study were divided into two-before training phase and after training phase. Training was given to the managers on Sepsis Six Bundles. The groups of the patients were also divided into two-control and experimental. The relation between the sepsis bundles and death of patients owing to septic shock was analysed. The results revealed that 36 of the patients died while 64 patients survived. Before and during the training period the compliance with the requirements of the Sepsis Six Bundle was limited, while the compliance increased rapidly after the training was completed. The patient outcomes were compared before and after training. This particular study thereby revealed that the Sepsis Six Bundle was effective in increasing the rate of survival among patients with septic shock and that proper training of nurses and other care providers is crucial for effective implementation and adherence to the bundle and improving patient outcome. The aim of this assignment is to also understand the role of training and education. Robson et al (2007) conducted a survey of ward nurse’s knowledge about sepsis and found that most nurses had very poor knowledge about sepsis, continuum of sepsis and its signs and symptoms which is one of major contributing factors for patient mortality. Most of the nurses in the study failed to recognise the first symptoms which led to delay in intervention (Robson et al, 2007). Studies have shown that adopting proper training and education and simulation based training can help in reducing both patient morbidity as well as patient mortality (Kyrkjebo et al, 2006; Safdar and Abad, 2008). The educational preparation and training of both trainee nurses and registered nurses is one of the major factors for reducing unnecessary sepsis related deaths (Tourangeau et al, 2006). The Sepsis Six Bundle includes several steps that appear relatively easy to follow, however nurses need to be given detailed information about each and every step to ensure proper implementation and positive patient otcomes. Critical care settings impose stressors on nurses, which can reduce efficiency in terms of care delivery and managementas workplace pressures can hamper their ability to make appropriate and prompt critical decisions. This mostly occurs owing to lack of clinical practice experience (Matlaka et al, 2014). Basic education in hand hygiene is regarded as the basic tool in preventing infections. Kelcikova et al (2012) studied the effectiveness of hand hygiene education among nurses and found that lack of hand hygiene education affects the compliance of the nurses in clinical practice settings.The Sepsis Six Bundle includes the use of catheters which are one of the prime reasons of transmission of diseases and play a key role in septic mortalities. In-dwelling urinary catheters are known to cause severe urinary tract infections while central venous catheters may cause severe infections as well (Sedor and Mullholland,1999, Zingg et al, 2008). Recommendations for critical care nurses Septic patients are often admitted to ICU andnursesplay a major role in prompt and methodical patient assessment at the outset of the problem by being able to recognise the observable hallmarks of sepsis. This needs to be followed by intervention strategies such as applying the prevention bundles to reduce sepsis mortality (Bernstein et al, 2013). The literature reviewrevealed that proper education and training can lead to proper diagnosis of sepsis and early intervention. However it has revealed certain gaps that the author believes t proper education can fill. In fact nurses being the immediate responders to patient health deterioration need to deliver the Sepsis Six Bundle carefully and accurately, which when accomplished can enable a single nurse to save 4 lives each passing hour (Daniels, 2012). Therefore the author has elicited the followingrecommendations for current clinical practice that on implemetation may aid proper channelling of the skills of nurses in optimising the standards and quality of care provided to patients presenting with sepsis: Education Since it is a basic aim to ensure that nurses or HCP’s are properly educated about sepsis, hallmarks of sepsis and intervention strategies it needs to be ensured that the nurses are given appropriate training and education with designated time to attend. Traditional education needs to be complemented with enhanced multi-faceted and interactional education. This could include visuals, hands-on education, real-life videos etc. Rather than just teaching through textbooks and seminars. A research study by Safdar and Abad (2008) have shown that implementation of multi-faceted and interactive educations could help in reducing problems in the healthcare setting. It is also recommended to use modern technology to introduce simulation based training for developing practice and decision-making skills (Lateef, 2010). Hands on training and proper education may also help in limiting the stressors in the practical clinical settings. Perhaps using online learning sepis education could be made mandatory, but also less time consuming for nurses to complete. Maintenance of proper nurse-patient ratio It needs to be brought into practice that each healthcare institution is have a good number of registered to and health care providers. Good staffing is extremely essential to have a positive impact on the patient outcomes regardless of the disease. However studies have shown that a low nurse-patient ratio contributes to high rates of infection and sepsis (Amravadi et al, 2000; Dimmick et al, 2001). Recognition and Diagnosing Since recognition and early diagnosis are the most important steps to control sepsis mortality it is recommended that the nursing staff is well informed about how to recognise SIRS infections and also understand the various methodologies to control them. Since it is the nurses who play the most important role they need to be provided with ample training in regards to proper assessment of the observable symptoms. Compliance with Sepsis Six Bundle It is firstly recommended that the nurses understand each and every point of the bundle and are 100% compliant to it (Plexman, 2011). Clinical audit to track compliance needs to be done at unpredicted times to gain a true reflection of adherence to the bundle. Perhaps there needs to be a sepsis link person in every clinical environment to update, conduct clinical audits and feedback the positives and negatives to the staff so that sepsis care can continue to have a positive impact. Infection Control Nurses need to come into contact with more than one patient and therefore the nurses need consider at least hygiene while dealing with each single patient especially those patients who have been diagnosed with sepsis. Studies have shown that adoption of hand anti-sepsis can help in bringing down infection transmission(Pratt et al, 2007).It is therefore recommended that the nurses wear gloves and change the gloves in case they come in contact with body fluids from the patient, proper hand washing in-between patients is also necessary regardless of the presence or absence of gloves. Nurses may also adopt disinfection through alcohol rubbing or washing with a strong anti-septic soap. Education regarding invasive lines to reduce blood line infections Since the Sepsis Six Bundle requires monitoring nurses or HCP’s need to be extremely careful while inserting, handling and removing invasive lines, such as: arterial lines, central venous catheters , PICCO lines or vascaths. Nurses should have the knowledge and skill to remove invasive lines when they are no longer required to reduce risk of indwelling line infections that could instigate sepsis. Furthermore, strictaseptic technique with insertion or removal of invasive lines should be inherent in clinical practice.. put with section above Urinary output monitoring is also essential and this calls for the use of a urinary catheter which is considered one of the most significant sources of nosocomial infections (Nicolle, 2008). It is therefore recommended that the time period for which the catheter is inserted be kept minimal. Unfortuantely critically ill patients require urinary catheterisation for longer due to the severity of their illness and monitoring purposes. Most critically ill patients are orally intubated. In such patients growth of microbial infections in the mouth is not uncommon (McNeill, 2000). Hence this is a major risk factor for sepsis. It is recommended that intubatedpatients be regularly assessed for oral problems, receive evidence based oral hygiene and that their cuff pressure is checked and maintained to reduce risk of aspiration and the oropharngeal region is suctioned regularyly. Rapid response to deterioration Early response is crucial to help treat sepsis and hence the rapid response system needs to be adopted. Nurses need to be skilled enough to accurately detect hallmarks of sepsis and act immediately. Early Goal Directed Therapy (EGDT) has to be implemented,especially in critically ill patients (Wan-Jie, 2014). It has been seen that failure to adopt (EGDT) has proven to show negative patient outcomes (Rivers et al, 2008). It is recommended that the nurses recognise the patients who are eligible for the EGDT i.e. that patient who fail to respond to the initial fluid resuscitation and refer them to outreach or the intensivist for transfer to Intensive Care. Conclusion The role of the nurse cannot be overlooked when it comes to providing the initial and basic care for patients. For critically ill patients supportive care improves their outcome drastically and hence the nurses need proper training and education to manage critically ill patients effectively. Sepsis is one of the most dangerous and life-threatening problems that exist today and one of the most basic ways to treat it is to recognise it early and intervene promptly. Studies have already established the fact that educating the nurses on the importance of detecting the onset of sepsis especially in ill patients can help reduce mortality rates. The Sepsis Six Bundle has proven to be a necessary and useful tool for prevention of death as a result of sepsis, when used appropriately, Each and every single step recommended in the bundle needs to be carried out with utmost care and within an hour. Presently clinical practice lacks opportunity for or proper organised training and education for HCP’s.. After having explored the literature, this assignment has provided some recommendations, which could be key to preventing sepsis related complications. It is not only knowledge, skill, experience and competence that nurses require, but they must also be mindful of their, duty of care and accountability in delivering evidence based care of the standard and quality expected from them (NMC, 2008). In addition to this nurses need to adhere to infection control measures as well as ensuring each shift they conduct a methodical health assessment of critically ill patients., Therefore, the author concludes that proper training and educational guidance in implementation and use of the Sepsis Six Bundle will not only help nurses play their role efficiently but also help in ensuring positive and improve outcomes for critically ill patients. The resource that I have done is a potential handy reference for nurses to identify risk of sepsis of a patient and also application of the Sepsis Six Bundle. (Refer, AppendixI). References Amaravadi.R, Dimick.J, Pronovost.P, et al.(2000).ICU nurse-to-patient ratio is associated with complications and resource use after esophagectomy. Intensive Care Medicine. 26,:1857-1862. Bone, R.C. et al (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101 (6): 1644-1655. Bone,R.C. et al. (1989). Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group.Critical Care Medicine, 17 (5),:389-393. Burney,M et al .(2012). 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Matlaka,M.C. et al.(2014). Challenges encountered by critical care unit managers in the large intensive care units. Original Research, p.1-7. McClelland, H and Moxon, A. (2014). Early identification and Treatment of Sepsis. Nursing Times, 110 (4):14-17. McNeill,H.E. (2000). Biting back at poor oral hygiene. Intensive and Critical Care Nursing, 16 (6):367-372. NHS England.(2014). Factsheet: Implementation of the ‘Sepsis Six’ care bundle. Online at http://www.england.nhs.uk/wp-content/uploads/2014/02/rm-fs-10-1.pdf on 15th January, 2015. Nicolle, L.E. (2008). The Prevention of Hospital-Acquired Urinary Tract Infection. Clinical Infectious Diseases, 46 (2):251-253. Pratt RJ, Petlowe CM, Wilson JA, et al (2007). EPIC2: National evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England. Journal of Hospital Infection, 65:S1-S64 Plexman,K.(2011). Nurses Making a Difference. American Journal of Critical care, 20 (6):424-425. Remick, D.G. (2007).Pathophysiology of Sepsis, American Journal of Pathology,170 (5):1435-1444. Rittirsch,D. et al.(2008). Harmful molecular mechanisms in sepsis. National Review in Immunology, 8 (10),776-787. Rivers,E.P. et al.(2008). Early goal-directed therapy in severe sepsis and septic shock: a contemporary review of the literature. Current Opinion in Anaethesiology, 21 (2):128-140Robinson, G (2013) Providing assurance, driving improvement. Cardiff: 1000 Lives Plus online at www.1000livesplus.wales.nhs.uk/sitesplus/documents/1011/Providing%20assurance%20driving%20improvement%20WEB.pdf .Accessed on 14th January, 2015. Robson,W. et al.(2012). An audit of ward nurses’ knowledge of sepsis .Nursing in Critical care, 12 (2):86-92. Safdar N, Abad C.(2008).Educational interventions for prevention of healthcare-associatedinfection: A systematic review. Critical Care Medicine, 36:.933-940. Sedor,J and Mullholland, S.G. (1999). Hospital-acquired urinary tract infections associated with the indwelling catheter. The urologic clinics of North America,26 (4):281-288. Tourangeau,A.E. et al.(2006). Impact of nursing on hospital patient mortality: a focused review and related policy implications. Quality and Safety in Health Care, 15 (1):4-8. Wn-Jai, G. et al.(2014). The effect of goal-directed therapy on mortality in patients with sepsis - earlier is better: a meta-analysis of randomized controlled trials. Critical Care, 18(5):570. Wu HP, Chen CK, Chung K, et al.(2009). Plasma transforming growth factor-β1 level in patients with severe community-acquired pneumonia and association with disease severity. Journal of Formosan Medical Association, 108:20-27. Zingg, W. et al.(2008). Central venous catheter-associated infections. Clinical. Anaesthesiology. 22 (3):407-421. APPENDIX I Read More