Management of Sepsis: Early Resuscitation

Sepsis and septic shock are critical conditions with high morbidity and mortality, resulting from a dysregulated host response to infection. This review explores the pathophysiology, clinical presentation, and management strategies for these conditions. Early recognition and intervention are key to improving outcomes, focusing on fluid resuscitation, antimicrobial therapy, and organ support. The article highlights the importance of a multidisciplinary approach, involving clinicians, nurses, pharmacists, and dietitians, to optimize patient care. Additionally, it delves into complications, prognostic factors, and long-term effects, providing insights for healthcare providers to enhance patient survival and recovery.

Shock, 2010

Hemodynamic instability plays a major role in the pathogenesis of systemic inflammation, tissue hypoxia, and multiple organ dysfunction in sepsis. Aggressive fluid replacement is one of the key interventions for the hemodynamic support in severe sepsis. In this scenario, the ability to restore the imbalance between tissue oxygen demand and supply, the heterogeneity in microcirculation, and endothelial dysfunction in the early stages of sepsis are associated with reduced mortality. In 2001, a single-center randomized controlled trial showed impressive reductions in hospital mortality when patients presenting to the emergency department with severe sepsis were treated with an aggressive protocol of fluids, blood transfusion, and inotropes aiming to improve tissue perfusion. However, external validation of this trial remains to be carried out. To date, there is no unequivocal evidence that such strategy is both universally feasible and effective. In the present article, we review the current evidence and comment on the future perspectives on early fluid resuscitation in severe sepsis.

Emergency Medicine Clinics of North America, 2013

Sepsis is a systemic inflammatory host response to infection characterized by nonspecific alternations in commonly measured physiologic parameters such as temperature, heart rate, respiratory rate, and blood pressure. The major initial challenges are rapid diagnosis of sepsis, identification of the underlying infection, and promptly initiating appropriate therapy. More than one third of septic patients arriving in the emergency department receive their initial therapy from prehospital personnel, and secondary transport of septic patients to regional referral centers is increasingly common. Therefore, transport personnel have a key role in the provision of initial therapy before hospital arrival and continuing therapies en route during interfacility transport. In this issue, we highlight recent literature that shows the potential impact of simple prehospital therapies such as fluid administration and the choice of fluid, provides some indication of the role early identification and testing modalities may play in this patient population, and raises questions about therapies many have adopted.

Virulence, 2014

Intensive Care Medicine, 2018

Objective: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock. Design: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations. Methods: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1-supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. Results: The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction? Conclusions: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

Intensive Care Medicine, 2008

Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

New England Journal of Medicine, 2015

Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 2007

Background: Fluid resuscitation is a key factor in restoring hemodynamic stability and tissue perfusion in patients with severe sepsis. We sought to examine associations of the quantity and type of fluid administered in the first six hours after identification of severe sepsis and hospital mortality, intensive care unit (ICU) mortality, and organ failure.