Severe Sepsis

Antonio F. Saad, MD


INTRODUCTION


PATHOPHYSIOLOGY OF SEPSIS


DEFINITION/DIAGNOSIS OF SEPSIS


TREATMENT


   • Hemodynamic Resuscitation


   • Occult Shock


SUMMARY


INTRODUCTION


Sepsis occurs as the result of a systemic maladaptive inflammatory response to an infectious insult. It is the leading cause of mortality in intensive care units (ICUs) in developed countries and the incidence is increasing worldwide.1 The literature regarding management of sepsis in the pregnant patient is limited and pregnant women have typically been excluded from landmark trials that have guided the management of sepsis over the last decades. Most cases of severe sepsis/septic shock are managed in ICUs and, therefore, obstetricians and maternal fetal medicine specialists are unfamiliar with management principles.


PATHOPHYSIOLOGY OF SEPSIS


The pathophysiology of sepsis is not completely understood. After exposure to a microorganism (bacteria, virus, parasite, fungi), the inflammatory cascade is activated. Massive production of inflammatory and anti-inflammatory cytokines together with endothelial derived factors like nitric oxide and other mediators like prostaglandins, leukotrienes, and complement lead to loss of vasomotor tone with profound vasodilation and increased vascular permeability (secondary to cytokine-induced endothelial injury) with subsequent third spacing. Edema in the extravascular compartment (interstitium, pleural and pericardial spaces, lung, brain, abdomen, heart walls) leads to increased total body water but decreased intravascular effective volume. Septic patients commonly appear edematous despite suffering from severe hypovolemia (especially during and immediately after aggressive fluid resuscitation). The profound decrease in systemic vascular resistances facilitates the so-called “increased cardiac output” seen in septic patients. However, the myocardium function in sepsis is also altered by the action of substances like nitric oxide, interleukin-1, oxygen-derived free radicals, and tumor necrosis factor α. The latter substances inhibit myocardial contractility leading to biventricular systolic dysfunction (up to 60% of patients with sepsis have an ejection fraction <45%). Both systolic and diastolic dysfunction may occur. Edema within the wall of the left ventricle leads to a “stiff” ventricle that will not expand adequately during diastole impending proper ventricular filling leading to congestive heart failure (diastolic dysfunction). Not infrequently, myocyte injury from proinflammatory cytokines may lead to leakage of troponins. Typically, patients with systolic dysfunction tend to present with biventricular dilation. The latter appears to be an adaptive response, as dilation will allow for more intracavitary filling leading to an increased stroke volume despite a decrease in ejection fraction (preload recruitment). These cardiac changes tend to resolve spontaneously among survivors of sepsis. Patients with isolated diastolic dysfunction usually have worse outcomes.


Almost all patients with severe sepsis have clotting abnormalities ranging from silent biochemical changes to full blown disseminated intravascular coagulopathy (DIC). Activation of the clotting cascade in sepsis results from tissue factor expression in mococytes, neutrophils, and the endothelium as part of the inflammatory response. Once tissue factor is expressed in the surface of these cells, it binds factor VII activating the clotting cascade through the extrinsic pathway. Development of DIC contributes to organ hypoperfusion (secondary to microvascular occlusion) and multiorgan failure. Platelet and clotting factor consumption leads to thrombocytopenia and prolongation of clotting times. Simultaneous activation of the fibrinolytic pathway leads to elevated levels of fibrin-fibrinogen degradation products and D-Dimer.


Another important pathway is that of activated protein C. Once thrombin is generated, it interacts with an endothelial surface receptor known as thrombomodulin. This interaction leads to activation of protein C, which inhibits clotting factors V and VIII, promotes fibrinolysis, and has anti-inflammatory properties. Cytokines decrease the activity of thrombomodulin, leading to a lack of protein C activity in sepsis and thus favoring thrombosis. Sepsis is a pro thrombotic state.


Mitochondrial dysfunction is also commonly seen in severe sepsis. Even in the presence of adequate oxygen delivery, adequate oxygen consumption cannot be guaranteed if the mitochondria is dysfunctional and cannot extract oxygen and use it in oxidative respiration. The latter explains why patients with sepsis may have normal or above normal saturations of hemoglobin in the central or pulmonary circulations despite adequate oxygen delivery.


In summary, sepsis is characterized by a massive inflammatory response leading to hypotension secondary to a decrease in systemic vascular resistances and increased vascular permeability, cardiac dysfunction, activation of the clotting cascade, inhibition of natural anticoagulant pathways, and mitochondrial dysfunction.


DEFINITION/DIAGNOSIS OF SEPSIS


The definition of sepsis has been modified dramatically in the last years. The American College of Chest Physicians and the Society of Critical Care Medicine introduced the concept of systemic inflammatory response syndrome (SIRS) in 1992.2


A patient is considered to have SIRS if 2 or more of the following criteria are present:


1. Temperature >38°C or <36°C


2. Heart rate >90 bpm


3. Respiratory rate >20 breaths/min or a PaCO2 <32 mmHg


4. White blood cell count >12,000/mm3 or <4000/mm3 or bandemia >10%


Sepsis has typically been defined as SIRS resulting from an infectious etiology. For example, a patient with pyelonephritis with a heart rate of 110 bpm and a respiratory rate of 26 breaths/min is considered to have sepsis.


Severe sepsis is defined as sepsis with signs of at least one organ dysfunction (eg, confusion, respiratory failure, acute kidney injury, thrombocytopenia, prolongation of clotting times, elevation of liver enzymes, ileus, hypotension).


Septic shock is defined as severe sepsis with hypotension despite adequate fluid resuscitation. These subsets of patients will require vasopressors to maintain hemodynamic stability.


This definition of sepsis has been criticized for being too sensitive and nonspecific, as most critically ill patients will meet SIRS criteria even in the absence of infection. Adding to the problem, physiologic changes of pregnancy may include a heart rate more than 90 bpm, a PaCO2 less than 32 mmHg, and a white blood cell count more than 12,000/mm3. This definition is even more nonspecific in the pregnant population.


In 2001, extended criteria for the diagnosis of sepsis were developed to improve the diagnostic accuracy of the clinical response to infection.3 Such signs and symptoms include confusion, pulmonary edema, oliguria, ileus, thrombocytopenia, prolonged clotting times, elevation of procalcitonin or C reactive protein, elevation of liver function tests, hyperglycemia, hypotension, lactate elevation, among others. The reader should understand that this list of signs is a guide and not all patients with sepsis will have them just as nonseptic patients may have some of them.


A fundamental principle in sepsis management is that the earlier the therapy is instituted, the better the outcomes will be. The clinician should suspect the presence of sepsis in any pregnant woman with an infectious process and some of the signs and symptoms listed. In general, any organ may be affected in sepsis (brain, lung, heart, bone marrow, kidney, liver, gut).


TREATMENT


Once the diagnosis of severe sepsis is established, early aggressive support is essential to achieve good outcomes. Many of the interventions described in the following paragraphs are commonly performed simultaneously.


Cultures should be obtained as clinically indicated (blood, urine, sputum, cerebrospinal fluid, vaginal secretions, wound collections, pleural fluid, amniotic fluid, abscess) ideally before starting broad-spectrum antibiotics. Broad-spectrum antibiotics (with coverage against gram positive bacteria, gram negative bacteria, and anaerobes) and immediate source control should be accomplished as soon as possible.4

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Jan 26, 2017 | Posted by in OBSTETRICS | Comments Off on Severe Sepsis

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