Journal of Pediatric Infectious Diseases - Volume 4, issue 2

Authors: Kissoon, Niranjan

Article Type: Research Article

DOI: 10.3233/JPI-2009-0159

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 69-69, 2009

Authors: Mangia, Cristina M.F. | Kissoon, Niranjan | Carcillo, Joseph A.

Article Type: Research Article

Abstract: Severe sepsis and septic shock are life-threatening diseases in both developed and developing countries and is an important risk factor for morbidity and mortality in all age groups. In developing countries, there is a direct relationship between the incidence of infections and mortality under five years of age. Child mortality in these scenarios is complex and involves issues such as lack of preventative care, malnutrition, poverty, and lack of resources, that together contribute to the increased …incidence and poor outcomes in sepsis. The concept of integrated management of childhood illness that involves the community, family and health systems is an important way that has been proposed for reduce children mortality and morbidity in developing nations and should be applied in sepsis initiatives. Sepsis and septic shock are observed time-sensitive, early diagnosis and prompt treatment have been related to good outcome. Actions such as prevention sound public health policies, educational programs for health care providers, family and community may help to reduce the global burden of this disease in children. Show more

Keywords: Severe infectio, sepsis, septic shock, epidemiology, mortality, children

DOI: 10.3233/JPI-2009-0157

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 71-76, 2009

Authors: Kissoon, Niranjan | Carcillo, Joseph A.

Article Type: Research Article

Abstract: Sepsis and septic shock are major contributors to mortality in children worldwide. While many factors may contribute to poor outcomes, resource limitations play a role in developing countries. However, early recognition and aggressive therapy using simple measures can reverse shock in most children. Indeed great gains have been realized in some areas with limited resources. In this manuscript, we outline the treatment of sepsis in children based on the resources available in various countries. This approach …forms the basis of the World Federation of Pediatric Intensive and Critical Care Societies sepsis initiatives. An invitation is extended to participate in this global sepsis initiative. Show more

Keywords: Sepsis, septic shock, children, treatment, outcome

DOI: 10.3233/JPI-2009-0152

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 77-84, 2009

Authors: Singhi, Sunit | Argent, Andrew C. | Baranwal, Arun K. | Santhanam, Indumathy

Article Type: Research Article

Abstract: Sepsis and septic shock are associated with significant mortality among children of developing economies. We review the current concepts in management of shock that are applicable to emergency room in resource poor setting. The emphasis is on simplified definition, early identification, and a time sensitive approach to reverse pathophysiological derangements using clinical endpoints.~Pathophysiology of septic shock includes hypoxemia, reduction in cardiac output and perfusion pressure, capillary shunting of blood past the tissue …beds and increased oxygen consumption. Early recognition of sepsis/septic shock is aided by presence of fever, lethargy, altered mental states, tachypnea, tachycardia, central-to-peripheral temperature difference, mottled or cool extremities, abnormal capillary refill and reduced urine output. The management recommendations based on evidence include resuscitation of airway and breathing (first 5 min), administration of 40–60 mL/kg normal saline (5–40 min), early initiation of inotrope infusion (dopamine, 10 μg/kg/min; epinephrine, 0.1–0.3 μg/kg/min), ventilation (when indicated) and administration of the first dose of antimicrobials (20–60 min). Some children may require up to 90–110 mL/kg saline in the first hours. Colloids may be considered in patients with malnutrition and malaria. Hypoglycemia should be identified and corrected at the earliest. Little evidence supports correction of hypocalcemia and use of packed red cells (if hemoglobin is < 10 g/dL) in initial resuscitation. Initial therapeutic endpoints includes normalization of tachypnea, tachycardia, systolic blood pressure, peripheral perfusion pressure, normal capillary refill, urine output > 1 mL/kg/hr, level of consciousness, hepatomegaly and central venous pressure > 10 cmH_{2} O. Subsequent endpoints to be targeted include normalization of central venous oxygen saturation, and blood lactate. Vasopressor (norepinephrine) and inodilators (dobutamine and milrinone), and packed red cells may be used for optimizing these indices of global consumption/delivery deficit of oxygen. Ventilation, manual or mechanical if available, should be used. Show more

Keywords: Children, emergency department, fluid resuscitation, septic shock, resource-limited setup

DOI: 10.3233/JPI-2009-0163

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 85-98, 2009

Authors: Singal, Mona | Mizuno, Yumiko | Skippen, Peter | Kissoon, Niranjan

Article Type: Research Article

Abstract: Early recognition of pediatric severe sepsis and septic shock followed by aggressive protocolized clinical management are the keys to improving mortality outcomes. Timely admission to the pediatric intensive care unit allows ongoing aggressive resuscitation, and early institution of targeted therapy guided by central venous pressure and mixed venous oximetry. This allows optimization of management according to changing hemodynamic patterns. Early application of lung protective strategies before the onset of an acute lung …injury, or after its development as well as management of acute kidney injury can reduce morbidity and mortality from sepsis. Increasing experience with extracorporeal membrane oxygenation and plasmapheresis may improve outcomes in septic shock in the future. Show more

Keywords: Sepsis, septic shock, intensive care, management, child

DOI: 10.3233/JPI-2009-0158

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 99-106, 2009

Authors: Ranjit, Suchitra | Kissoon, Niranjan | Shamarao, Shivkumar

Article Type: Research Article

Abstract: Dengue viral infections are caused by one of four single stranded RNA viruses of the family Flaviviridae. They can occur virtually throughout the tropics and are transmitted by their mosquito vector, Aedes aegypti. Dengue, the most common arboviral disease in the world, has become more prevalent now than ever before and its prevalence is expected to increase. The risk for severe disease is determined by a complex interplay of epidemiological, virus and host factors. The …clinical syndromes caused by dengue viral infections occur in an iceberg fashion along a severity continuum. Most cases are asymptomatic and a much smaller proportion present with severe forms of the disease-dengue hemorrhagic fever/dengue shock syndrome-that are characterized by sudden increase in vascular permeability and consequent shock. The traditional WHO classification and grading of dengue fever, dengue hemorrhagic fever and dengue shock syndrome are described along with a discussion of the timing and methods of laboratory diagnosis. Management is predominantly supportive. In patients with severe shock, treatment strategies are double pronged and include methods to judiciously resolve shock and control bleeding while simultaneously preventing fluid overload and its complications, including the need for assisted ventilation. These considerations are especially relevant in resource limited tropical countries where dengue viral infections are amongst the leading causes of childhood hospitalization, morbidity and death. Show more

Keywords: Dengue, dengue hemorrhagic fever, dengue shock syndrome, shock, dengue immunopathogenesis, dengue diagnosis, management of shock, prevention of fluid overload

DOI: 10.3233/JPI-2009-0164

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 107-117, 2009

Authors: Felmet, Kate | Choong, Karen | Kissoon, Niranjan

Article Type: Research Article

Abstract: Endocrine dysfunction is common in severe sepsis and is associated with increased morbidity and mortality risk. Clinical detection of this heterogenous disorder is limited, and the accuracy of laboratory diagnosis is complicated by the limitations in hormonal assays and the variable definitions used in its diagnosis. This article reviews the common hormone therapies that have been evaluated in the critically ill patient with sepsis, namely corticosteroids, vasopressin and insulin. There are numerous adult clinical …trials in this area, some of which have revealed conflicting results. Pediatric data is much more limited. We present current recommendations for hormone therapy in adults and children, but caution that further study is needed to better understand the dynamic and complex endocrine responses during septic shock, and to develop improved methods for diagnosis and monitoring of patient response, so that we can determine not only which therapies to use, but how, in what combinations, and in which patients. Show more

Keywords: Hormone, corticosteroids, vasopressin, insulin, sepsis

DOI: 10.3233/JPI-2009-0153

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 119-126, 2009

Authors: Hall, Mark W. | Muszynski, Jennifer A.

Article Type: Research Article

Abstract: The vast majority of morbidity and mortality from sepsis can be attributed to the host immune response to infection rather than the infection itself. The innate and adaptive immune systems both contribute to this process. Numerous therapies aimed at reducing the pro-inflammatory burden of acute sepsis have been studied in clinical trials, with most producing disappointing results. The inflammatory response to sepsis has since been shown to be highly dynamic, with a period of compensatory down-regulation …of the pro-inflammatory response dominating in the subacute phase of illness. This state, when prolonged and severe, is termed immunoparalysis and is associated with increased risks for nosocomial infection and death. Early evidence suggests that this state may be reversible with beneficial effects on outcomes. Other strategies for manipulating the inflammatory response in the setting of sepsis include the use of corticosteroids, immunonutrition, extracorporeal therapies, intravenous immunoglobulin, and the modulation of pre-existing immunosuppressive drugs. Clinical trials investigating immune modulation in sepsis have largely been done without the benefit of prospective immune monitoring and have rarely been done in children. Immune phenotype-directed therapies aimed at restoring immunologic homeostasis in pediatric sepsis represent the next step on the path toward improving sepsis outcomes in children. Show more

Keywords: Immune modulation, inflammation, immunoparalysis, sepsis

DOI: 10.3233/JPI-2009-0154

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 127-136, 2009

Authors: Nguyen, Trung C. | Han, Yong Y. | Fortenberry, James D. | Carcillo, Joseph A.

Article Type: Research Article

Abstract: Sepsis is a systemic inflammatory syndrome in response to an infection. With the current resuscitation practice, up to 16% of children with severe sepsis and septic shock still progress to develop multiple organ failure (MOF), a condition that is associated with poor outcome. In this review, we focus on the thrombotic microangiopathic paradigm for the development of sepsis-induced MOF. We describe the clinical observations, emerging experimental and laboratory evidence supporting the concept that sepsis-induced …MOF may be a secondary thrombotic microangiopathy, manifest as thrombocytopenia-associated MOF. Drawing the pathologic similarities such as a disintegrin and metalloprotease with thrombospondin motifs-13 deficiency, impaired ultra-large von Willebrand factor multimers proteolysis, and von Willebrand factor-rich microthrombi and therapeutic success with plasma exchange in treating thrombotic thrombocytopenic purpura, a primary thrombotic microangiopathy, we propose a rationale for the role of plasma exchange therapy for sepsis and thrombocytopenia-associated multiple organ failure. Show more

Keywords: Sepsis, ADAMTS-13, von Willebrand factor, thrombocytopenia, multiple organ failure, plasma exchange, thrombotic microangiopathy, TAMOF

DOI: 10.3233/JPI-2009-0155

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 137-145, 2009

Authors: Sun, Bo | Xu, Feng | Yu, Wenliang

Article Type: Research Article

Abstract: Sepsis and septic shock is one of the major death causes in Chinese pediatric critical care. This review has brought to this issue with very recent advances in clinical investigation of this aspect published in Chinese literature. In this report, management of sepsis, severe sepsis and septic shock as well as other complications were carried out in both multicenter or single center studies, mostly according to international definitions and recommendations for sepsis and septic shock. The …resources of these reports, though not complete, represent the different regions with leading pediatric critical care centers, well reflecting progression of pediatric critical care in both newly industrialized and emerging regions of China. Show more

Keywords: Multiple organ dysfunction syndrome, pediatric intensive care unit, respiratory failure, sepsis, septic shock, systemic inflammatory response syndrome

DOI: 10.3233/JPI-2009-0156

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 147-152, 2009

Authors: Sherlock, Rebecca

Article Type: Research Article

Abstract: The aim of this paper is to highlight the current trends in the epidemiology, investigation, management and prognosis of neonatal sepsis and septic shock. Despite the historical prevalence of group B streptococcal neonatal infections, due to Centers for Disease Control and Prevention guidelines for the prevention of perinatal group B streptococcal disease, Escherichia coli is currently the most common organism isolated in early-onset neonatal sepsis. Furthermore, there is increasing evidence that …antibiotic resistant strains are on the rise. With respect to late-onset neonatal sepsis, coagulase-negative Staphylococcus is responsible for the majority of late-onset infections, followed by Candida species. An evolving pathogen likely to increase in prevalence is methicillin-resistant Staphylococcus aureus. The clinical presentation of sepsis varies while the presentation of septic shock consists of respiratory distress and poor perfusion especially in the context of antenatal risk factors. There exist a number of ancillary investigations that can be useful in the evaluation of a neonate with sepsis, including C-reactive protein, interleukin-6 and procalcitonin. The utility of these are discussed. The mainstays of management of a neonate with septic shock include empiric then definitive antibiotic therapy, cardiovascular support with fluids and/or inotropes and respiratory support. The prognosis and outcomes for infants with septic shock are guarded and neurodevelopmental functioning may be impaired in survivors. Show more

Keywords: Neonate, sepsis, shock, GBS, inotropes, prognosis

DOI: 10.3233/JPI-2009-0161

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 153-159, 2009

Authors: Argent, Andrew C. | Eley, Brian

Article Type: Research Article

Abstract: Consensus definitions of pediatric sepsis clearly include viral infections, and yet most studies of sepsis in the intensive care environment specifically exclude viral infections. Viral infections are a common cause of admission to the pediatric or neonatal intensive care. They are probably underestimated, and new techniques of viral identification offer an opportunity to expand our understanding of the true impact of viral infections on critical illness in childhood. Not only are viral infections a cause of …admission, but they may also constitute a significant component and risk of nosocomial infections in the pediatric intensive care unit. Specific antiviral therapies are limited, and in many cases immunization and prevention is the most effective approach to severe viral infections. With climate changes, the distribution of insect borne viral infections is changing across the world and these infections are starting to occur in new geographical areas. Attention has to be paid to the issue of protection of pediatric intensive care staff against viral infections. Show more

Keywords: Viral sepsis, children, intensive care

DOI: 10.3233/JPI-2009-0160

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 161-172, 2009

Authors: Singhi, Sunit | Khilnani, Praveen | Lodha, Rakesh | Santhanam, Indumathi | Jayashree, M. | Ranjit, Suchitra | Ramachandran, Bala | Ali, Uma | Sachdev, Anil | Chugh, Krishan | Udani, Soonu | Uttam, Rajiv | Deopujari, Satish | Kissoon, Niranjan

Article Type: Research Article

Abstract: WHO 2005 data points to sepsis in form of pneumonia, diarrhea, and neonatal sepsis as major killers of children in the resource limited countries of Asia and Africa, However, currently there are no specific published guidelines for treatment of severe sepsis in resource limited circumstances. An expert panel drawn from all over India, met to discuss and draw guidelines for management of pediatric septic shock that are applicable to resource limited countries. The group evaluated strength …of published data and expert opinion for clinical practice and feasibility of delivery of care at various levels of resource constraints, keeping in view unique patient population and limited availability of equipment and resources. Issues for discussion included simplified definitions and reliable clinical indicators of septic shock, fluid resuscitation, graded inotropic and vasopressor support, corticosteroid therapy, timing and indication for endotracheal intubation and use of positive end expiratory pressure/mechanical ventilation, initial empirical antibiotic therapy, correction of hypoglycemia and glycemic control, role of immunoglobulin, and blood and blood products. Evidence has been graded and levels of evidence indicated wherever applicable. The expert group recognized and listed potential barrier to implementation of existing American College of Critical Care Medicine guidelines for treatment of septic shock in resource limited countries, adopted simplified definitions of septic shock, tachycardia, tachypnea and hypotension, and developed step-wise algorithmic approach for treating septic shock. Evidence based treatment recommendations include early oxygen therapy, fluid resuscitation based on blood pressure, use of dopamine in fluid refractory shock, early use of antibiotics, early intubation and assisted ventilation, correction of hypoglycemia and emphasis on use of physical examination for achieving therapeutic endpoints. These interventions have brought the mortality down and can be easily applied even at primary and/or secondary level health facilities. Interventions recommended after above steps were based on consensus rather than evidence. These include stress dose steroid therapy, use of vasopressors and inodilators, and central venous pressure and echocardiography to guide fluid and vasoactive drug infusion, which require transfer to a pediatric intensive care unit. Strict glycemic control is not recommended. Evidence on benefit of several other interventions viz. use of vasopressin as vasopressor, use of intravenous immunoglobulins, renal replacement therapy, use of plasmapheresis etc. is emerging. The expert group observed that further research evaluating individual components of guidelines and relative benefit of each of these interventions in resource limited setting is needed, as also the benefit of adherence with standardized protocol. Pediatric sepsis guidelines suitable for resource limited settings are presented for resource limited settings. Several unresolved issues were identified for further research. Show more

Keywords: Children, emergency care, septic shock, fluid resuscitation, vasoactive drugs

DOI: 10.3233/JPI-2009-0162

Citation: Journal of Pediatric Infectious Diseases, vol. 4, no. 2, pp. 173-192, 2009