Management of Septic Shock

Severe sepsis is a common disease process affecting some 2-11% of hospital admissions in the US. Severe sepsis and septic shock are associated with considerable morbidity and mortality, and account for a large part of intensive care unit costs. Until recently, the management of septic shock relied on the treatment of underlying infection with antimicrobial agents and surgical removal of any infectious source, and individual support of failing organs. However, in the last few years we have seen huge strides being made in our understanding of the pathophysiology of the sepsis response, and in our ability to manipulate that response. In the last couple of years these advances have come to fruition with the development of a drug, drotrecogin alfa, which specifically reduces mortality from this all too often fatal disease. While intensive early resuscitation remains the cornerstone of management, new approaches are beginning to form part of sepsis management protocols and will lead to improved outcomes for patients with this disease process.     

Management of septic shock

Severe sepsis is a common disease process affecting some 2-11% of hospital admissions in the US. Severe sepsis and septic shock are associated with considerable morbidity and mortality, and account for a large part of intensive care unit costs. Until recently, the management of septic shock relied on the treatment of underlying infection with antimicrobial agents and surgical removal of any infectious source, and individual support of failing organs. However, in the last few years we have seen huge strides being made in our understanding of the pathophysiology of the sepsis response, and in our ability to manipulate that response. In the last couple of years these advances have come to fruition with the development of a drug, drotrecogin alfa, which specifically reduces mortality from this all too often fatal disease. While intensive early resuscitation remains the cornerstone of management, new approaches are beginning to form part of sepsis management protocols and will lead to improved outcomes for patients with this disease process.     

临床感染性休克:我知道吗？

感染与休克，似乎是临床上人人都知道，人人都需要面对的问题。近年来, 临床对感染、休克与感染性休克之间的相互联系及其变化关系有了更为深刻的认识和理解，进而导致治疗理念和方法出现近乎天翻地覆的变化。今天的治疗方法在许多方面可能与昨天大不相同，正确掌握和运用这些方法可以带来意想不到的预后改善。感染性休克是一种常见、多发、高致死率的临床综合征，但是，如果在整个治疗过程中正确完成每一项临床干预措施，感染性休克是可以治愈甚至预防的。     

The role of surgery in the management of septic shock--extra-abdominal causes of sepsis

Septic shock is a severe inflammatory response to one or more pathogenic micro-organisms. When a person's immune response is excessively intense, a cascade of phenomena may be activated that ultimately is harmful. Appropriate management of septic shock may include surgical intervention to remove or neutralize the septic focus in an effort to treat the inflammatory response cascade. This is the first of two articles presenting current information on the role of surgery in the management of a patient with septic shock. This article describes extra-abdominal sources of sepsis.     

Hepatitis C-HIV coinfection: current and future therapy

Coinfection with hepatitis C in HIV-infected patients has been reported in 15-70% of patients depending on the mode of acquisition of both viruses. As recent advances in HIV-directed antiviral therapy have markedly delayed HIV progression and mortality, the incidence of complications arising from hepatitis C-associated liver disease in coinfected patients is increasing exponentially. The interaction of HIV and hepatitis C is complex. It is clear that HIV infection negatively affects the natural history of hepatitis C, while HIV-directed therapy may enhance immunologic response and exacerbate hepatocellular injury induced by hepatitis C via immune reconstitution. In this review, the pathobiology, inter-relation of hepatitis C and HIV infection in coinfected patients as well as present and future treatment in this unique patient population are discussed.     

Hepatitis C–HIV coinfection: current and future therapy

Coinfection with hepatitis C in HIV-infected patients has been reported in 15–70% of patients depending on the mode of acquisition of both viruses. As recent advances in HIV-directed antiviral therapy have markedly delayed HIV progression and mortality, the incidence of complications arising from hepatitis C-associated liver disease in coinfected patients is increasing exponentially. The interaction of HIV and hepatitis C is complex. It is clear that HIV infection negatively affects the natural history of hepatitis C, while HIV-directed therapy may enhance immunologic response and exacerbate hepatocellular injury induced by hepatitis C via immune reconstitution. In this review, the pathobiology, inter-relation of hepatitis C and HIV infection in coinfected patients as well as present and future treatment in this unique patient population are discussed.     

Leptospirosis with pulmonary haemorrhage and multiple organ failure: a case report and literature review

Pulmonary haemorrhage is an important complication of leptospirosis. We herein report an uncommon case of severe pulmonary haemorrhage and multiple organ failure caused by leptospirosis in a 49-year-old man who was previously healthy. He was a farm worker who was admitted to the hospital because of haemoptysis. He had worked in a paddy field 4 days prior to admission. Chest computed tomography revealed pulmonary haemorrhage, which rapidly deteriorated into haemorrhagic shock and multiple organ failure. Based on the patient’s possible history of contact with contaminated water and the DNA sequence of Leptospira detected in his bronchoalveolar lavage fluid, the patient was diagnosed with pulmonary haemorrhagic leptospirosis. Despite the administration of a fluid bolus, norepinephrine, broad-spectrum antibiotics, and haemostatics, and even with administration of a blood transfusion and extracorporeal life support, the pulmonary haemorrhage could not be controlled effectively. The patient eventually died of haemorrhagic shock. Leptospirosis can be a life-threatening disease despite aggressive treatment, even with extracorporeal life support. Next-generation sequencing can provide important diagnostic clues for patients with atypical leptospirotic symptoms.     

Monocyte deactivation-rationale for a new therapeutic strategy in sepsis

Inflammatory cells, in particular monocytes/macrophages, release pro-inflammatory mediators in response to several infectious and non-infectious stimuli. The excessive release of these mediators, resulting in the development of whole body inflammation, may play an important role in the pathogenesis of sepsis and septic shock. TNF-alpha, acting synergistically with cytokines such as IL-1, GM-CSF and IFN-gamma, is the key mediator in the induction process of septic shock, as shown in several experimental models. Based on this concept and on the encouraging results obtained in several experimental models, a number of clinical sepsis trials targeting the production or action of TNF-alpha or IL-1 have been performed in recent years. Unfortunately, these trials have failed to demonstrate a therapeutic benefit. One reason for this may be the lack of exact immunologic analyses during the course of septic disease. Recently, we demonstrated that there is a biphasic immunologic response in sepsis: an initial hyperinflammatory phase is followed by a hypo-inflammmatory one. The latter is associated with immunodeficiency which is characterized by monocytic deactivation, which we have called “immunoparalysis”. While anti-inflammatory therapy (e.g. anti-TNF antibodies, IL-1 receptor antagonist, IL-10) makes sense during the initial hyperinflammatory phase, immune stimulation by removing inhibitory factors (plasmapheresis) or the administration of monocyte activating cytokines (IFN-gamma, GM-CSF) may be more useful during “immunoparalysis”.     

Beware of babesiosis: A rare and severe case causing death

Babesiosis is an infectious disease caused by protozoa of the genus Babesia which is primarily transmitted by tick vectors. Most cases are asymptomatic or only mild to moderate, but some cases may be severe causing death. A 57?year old male with no reported travel outside the country was escorted by Emergency Medical Services to our Pennsylvania hospital in July of 2018 presenting with hypoglycemia, jaundice, and hypotension. Initial assessment further revealed the patient to be severely hypothermic. Resuscitative efforts began immediately and the laboratory reported parasites observed on the patient's peripheral blood smear. The patient was admitted to the intensive care unit with severe septic shock and disseminated intravascular coagulation. The patient was ultimately transferred to a tertiary care center for exchange transfusion therapy and veno-arterial extracorporeal membrane oxygenation support, but expired 36?h after presentation. Current CDC data reflects a steady rise of tick borne disease in the United States, but as of 2016 there have been no reported cases of babesiosis in the state of Pennsylvania, let alone fatalities. Clinicians need to be aware of the risk of fulminant illness when practicing in known endemic regions.     

Application of microarrays to the analysis of gene expression in cancer

Molecular diagnostics is a rapidly advancing field in which insights into disease mechanisms are being elucidated by use of new gene-based biomarkers. Until recently, diagnostic and prognostic assessment of diseased tissues and tumors relied heavily on indirect indicators that permitted only general classifications into broad histologic or morphologic subtypes and did not take into account the alterations in individual gene expression. Global expression analysis using microarrays now allows for simultaneous interrogation of the expression of thousands of genes in a high-throughput fashion and offers unprecedented opportunities to obtain molecular signatures of the state of activity of diseased cells and patient samples. Microarray analysis may provide invaluable information on disease pathology, progression, resistance to treatment, and response to cellular microenvironments and ultimately may lead to improved early diagnosis and innovative therapeutic approaches for cancer.     

Nutritional support and gastrointestinal disease

The use of nutritional support in patients with acute gastrointestinal disease requires a thorough knowledge of the pathophysiology and nutritional alterations that are caused by the disease process. Although nutritional therapy of a patient with gastrointestinal disease is not curative of the underlying disease, it does provide essential support to the patient, which improves response to, and eventual recovery from, illness. Special considerations need to be made to avoid complicating the patient's condition by inappropriate use of nutritional support solutions, which can lead to abnormal liver function.     

Prostate Carcinoma Metastatic to the Stomach: Report of Two Cases and Review of the Literature

We report two cases of prostate carcinoma metastatic to the stomach. In the first case, the patient had indolent disease before presenting with gastric metastasis. The patient responded to treatment with resolution of gastrointestinal bleeding and other symptoms. In the second case, the patient developed aggressive prostate carcinoma while on immunosuppressive therapy following kidney transplant. His tumor became widely systemic, and he ultimately died of his disease. Although rare, the possibility of prostate carcinoma metastatic to the stomach should be considered when a patient with a history of prostatic adenocarcinoma presents with gastrointestinal symptoms.     

Managing atopic dermatitis in children and adults

Although the etiology of atopic dermatitis is not well understood, it appears to be linked to a combination of genetic and environmental factors, and it is usually associated with other atopic diseases such as asthma and hay fever. A definitive diagnosis in children and adults depends on identifying the nature and distribution of the lesions and on eliciting a personal or family history of the disease. Although no cure exists, atopic dermatitis often resolves spontaneously and can be controlled through proper management. Avoiding factors that precipitate or exacerbate inflammation is key to preventing disease flares. In children and adults, hydration and topical corticosteroids are the mainstays of therapy. Current advances in understanding the immunologic basis of the disease have led to the development of highly effective new treatments. Using patient education and support, the clinician can help adults and children successfully manage their disease.     

Breaking through a plateau in renal cell carcinoma therapeutics: development and incorporation of biomarkers

With the Food and Drug Administration approval of 6 novel targeted agents since December 2005 and limited comparative trials to discern relative efficacy, the treatment of metastatic renal cell carcinoma (RCC) has become immensely complex. The research community must look to novel ways in which to identify appropriate candidates for selected targeted therapies; one potential strategy is the use of clinical and molecular biomarkers. A growing body of knowledge-related von Hippel Lindau-driven pathways in this disease has highlighted the potential role of hypoxia-inducible factor subtypes in distinguishing RCC patients clinically. Techniques applied in other malignancies, such as gene expression and proteomic profiling, may also ultimately allow for clinical stratification. An emerging understanding of immunologic phenomena that may affect cancer progression (i.e., tumor infiltration by CD68 lymphocytes, memory T-cells, etc.) has unveiled a number of other potential biomarkers of response. Several vascular endothelial growth factor receptor-directed therapies classically thought to function as antiangiogenics may also have complex effects upon the tumor microenvironment including the associated immune cell milieu. As such, immunologic parameters could potentially predict response to current therapies. Finally, clinical biomarkers, such as hypertension, may predict the efficacy of several currently available targeted agents, although implementation of such biomarkers remains challenging. Herein, the clinical relevance of putative RCC biomarkers is examined in detail.     

Teaching patients with peripheral vascular disease.

The teaching of a patient with peripheral vascular disease offers many challenges to the nurse. Although content should be understood and utilized by the patient and significant others, of primary importance is the belief that the learner is the curriculum and that his perception of self and his problems is the focus of teaching. The learning needs generally should be considered as the needs of an adult individual, who has many past experiences and an interest in the present and future. This patient may experience pain from his disease and may require the assistance and support of others. If the purpose of treatment is to improve circulation and prevent trauma and infection, then patient instruction must be recognized as a vital tool in therapy. But the nurse cognizant of the progressiveness of peripheral vascular disease must capitalized on the teachable moments--when the patient is ready and the learning is needed.     

Novel potential therapies for septic shock

Sepsis is the systemic inflammatory response syndrome secondary to a local infection. Septic shock, the severe complication of sepsis associated with refractory hypotension, is frequently a near-fatal condition requiring prompt diagnosis and management. Although the recent years have been associated with considerable improvements in the knowledge of the pathophysiology of the disease and remarkable advances have been achieved in sepsis treatment, the morbidity and mortality of this disease are still unacceptably high. In this review, we will briefly discuss the ongoing standard treatment of septic shock and describe novel potential therapies, aiming to improve hemodynamic support and/or control inflammatory response in sepsis. These therapies were associated with benefits in experimental studies and have been tested or are currently under testing in randomized controlled studies with septic patients.     

Negative pressure ventilation: new uses for an old technique

Negative pressure ventilation (NPV), a concept that was used in the 1940s through 1950s to support the victims of the polio epidemic, is regaining popularity. It is being used increasingly to intermittently support respiratory function in patients suffering from a variety of diseases. The use of NPV obviates the need for a surgically placed airway (if the patients' upper airway is intact) and allows the patient to resume many of his or her normal activities. Several types of NPV are available for use and experimentation, and it is strongly recommended that the appropriate type for each patient be chosen. Nursing care of the patient on NPV is essentially the same as that of any chronically ventilator-dependent patient. Issues unique to the patient supported on NPV include: increased potential for aspiration, skin breakdown around the NPV site, and "tank shock." Nursing plays an important role in identifying patients who may be candidates for NPV. Negative pressure ventilation may allow a formally hospital-bound patient the opportunity to be home with family and friends.     

Decrease in circulating dendritic cells predicts fatal outcome in septic shock

Objective Biomarkers allowing accurate early staging of septic shock patients are lacking despite their obvious interest for patient management. Experimental models of septic shock in mouse previously noted a decrease in dendritic cell numbers. The aim of the study was to find a rapid reproducible biological test for an assessment of disease severity. Design Evaluation of peripheral blood dendritic cell counts by flow cytometry using three commercially available kits. Patients and participants Forty-two consecutive septic shock patients were studied prospectively. Measurements and results Early low dendritic cell counts were correlated to disease severity as assessed by Simplified Acute Physiology Score or Sequential Organ Failure Assessment and predicted fatal outcome. The correlation was still present when the results were adjusted for age. Conclusion The monitoring of blood dendritic cell count may provide an early and valuable assessment of the severity of the host response against infection and may influence the therapeutic management of septic shock patients. O. Guisset and M.-S. Dilhuydy contributed equally to this work.     

Transfusion‐related immunomodulation: review of the literature and implications for pediatric critical illness

Transfusion‐related immunomodulation (TRIM) in the intensive care unit (ICU) is difficult to define and likely represents a complicated set of physiologic responses to transfusion, including both proinflammatory and immunosuppressive effects. Similarly, the immunologic response to critical illness in both adults and children is highly complex and is characterized by both acute inflammation and acquired immune suppression. How transfusion may contribute to or perpetuate these phenotypes in the ICU is poorly understood, despite the fact that transfusion is common in critically ill patients. Both hyperinflammation and severe immune suppression are associated with poor outcomes from critical illness, underscoring the need to understand potential immunologic consequences of blood product transfusion. In this review we outline the dynamic immunologic response to critical illness, provide clinical evidence in support of immunomodulatory effects of blood product transfusion, review preclinical and translational studies to date of TRIM, and provide insight into future research directions.