Sepsis and Multiorgan Failure



Sepsis and Multiorgan Failure


Marie Mullen




“Hectic fever (sepsis) at its inception is difficult to recognize but easy to treat. Left untended, it becomes easy to recognize but difficult to treat.”

— Niccolo Machiavelli (1498)

I. GENERAL PRINCIPLES

A. Definitions.

1. Systemic inflammatory response syndrome (SIRS).

a. Clinical response to nonspecific injury, including trauma, burns, infection, pancreatitis, or alternative inflammatory insult.

b. Clinical components of SIRS (two elements required to define).

i. Temperature ≥38°C or ≤36°C.

ii. Heart rate ≥90 per minute.

iii. Respirations ≥20 per minute.

iv. Leukocyte count >12,000 or <4,000 or >10% bands.

v. PaCO2 < 32 mm Hg.

2. Sepsis.

a. Documented or suspected infection and evidence of clinical inflammatory response.

b. 1992 criteria—Two or more SIRS criteria with associated infection define sepsis.

c. 2001 criteria—Documented or suspected infection with some markers of inflammation (Table 117-1).

3. Severe sepsis.

a. Sepsis with associated organ dysfunction or tissue hypoperfusion (Table 117-2).

4. Septic shock.

a. Sepsis with refractory hypotension after appropriate fluid resuscitation.

b. Suggested appropriate resuscitation of at least 30 mL/kg crystalloid minimum to be considered refractory.

5. Multiple-organ dysfunction syndrome (MODS).









TABLE 117-1 Diagnostic Criteria Sepsis
































Infectiona, documented or suspected, and some of the following:b,c


General variables

Fever (core temperature >38.3°C)


Hypothermia (core temperature <36°C)


Heart rate >90 min−1 or >2 SD above the normal value for age


Tachypnea


Altered mental status


Significant edema or positive fluid balance (>20 mL/kg over 24 h)


Hyperglycemia (plasma glucose >120 mg/dL or 7.7 mmol/L) in the absence of diabetes


Inflammatory variables

Leukocytosis (WBC count >12,000 µL−1)


Leucopenia (WBC count <4,000 µL−1)


Normal WBC count with >10% immature forms


Plasma C-reactive protein >2 SD above the normal value


Plasma procalcitonin >2 SD above the normal value


Hemodynamic variables

Arterial hypotensionb (SBP <90 mm Hg, MAP <70, or an SBP decrease >40 mm Hg in adults or <2 SD below normal for age)


SvO2> 70%b


Cardiac index >3.5 L·min−1·M−23


Organ dysfunction variables

Arterial hypoxemia (PaO2/FIO < 300)


Acute oliguria (urine output <0.5 mL·kg−1·h−1 or 45 mmol/L for at least 2 h)


Creatinine increase >0.5 mg/dL


Coagulation abnormalities (INR >1.5 or aPTT >60 s)


Ileus (absent bowel sounds)


Thrombocytopenia (platelet count <100,000 µL−1)


Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 mmol/L)


Tissue perfusion variables

Hyperlactatemia (>1 mmol/L)


Decreased capillary refill or mottling


a Infection defined as a pathologic process induced by a microorganism.

b SvO2 saturation >70% is normal in children (normally, 75%-80%), and CI 3.5-5.5 is normal in children; therefore, NEITHER should be used as signs of sepsis in newborns or children.

c Diagnostic criteria for sepsis in the pediatric population are signs and symptoms of inflammation plus infection with hyper- or hypothermia (rectal temperature >38.5°C or <35°C), tachycardia (may be absent in hypothermic patients), and at least one of the following indications of altered organ function: altered mental status, hypoxemia, increased serum lactate level, or bounding pulses.
WBC, white blood cell; SBP, systolic blood pressure; MAP, mean arterial blood pressure; SvO2, mixed venous oxygen saturation; INR, international normalized ratio; aPTT, activated partial thromboplastin time.
Source: From Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250-1256.










TABLE 117-2 Elements Suggestive of Organ Failure







Sepsis-induced hypotension


Lactate greater than the upper limits of normal laboratory results


Urine output < 0.5 mL/kg/h for >2 h, despite adequate fluid resuscitation


ALI with PaO2/FIO2 <250 in the absence of pneumonia as infection source


ALI with PaO2/FIO2 <200 in the presence of pneumonia as infection source


Creatinine > 2.0 mg/dL (176.8 mol/L)


Bilirubin > 2 mg/dL (34.2 mol/L)


Platelet count <100,000


Coagulopathy (INR > 1.5)


Dellinger RP, Levy M, Rhodes A et al., Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock. 2012 Crit Care Med 2013;41(2):580-637.


a. Disease spectrum in which one or more organ systems are unable to maintain homeostasis without support in an acutely ill patient.

b. MODS has many potential sources. Sepsis is one of the most common (Table 117-3).

B. Epidemiology.

1. Severe sepsis represents 20% of all ICU admissions in the United States (US).

2. Severe sepsis is the number one cause of death in the non-coronary care ICU and the 10th leading cause of death in the US.

3. Severe sepsis has an estimated 28% to 50% mortality rate.

4. Septic shock has an estimated mortality of 60%.

5. MODS is a leading cause of death in the ICU. Depending on the number of organ systems involved, MODS can carry an 80% mortality rate.

II. PATHOPHISIOLOGY

A. Infection.

1. Sepsis is an overwhelming and complicated proinflammatory response to infection.

2. Inciting organisms have changed with time. Change is connected to drug resistance.

3. Gram-negative and gram-positive organisms are each separately linked to 25% of sepsis-related infections.

4. Mixed gram-negative and gram-positive infections account for about 15% of causative infections.

5. Fungi associated with 5% to 10% of infections.

B. Pathogen induction.

1. Inflammatory response starts with recognition of pathogen molecular components by receptors on cells of the innate immune system.









TABLE 117-3 Risk Factors for MODS








































Infection

Peritonitis and intra-abdominal infection


Pneumonia


Necrotizing soft tissue infections


Tropical infections (e.g., falciparum malaria, typhoid fever, dengue fever)


Inflammation

Pancreatitis


Ischemia

Ruptured aortic aneurysm


Hemorrhagic shock


Mesenteric ischemia


Immune reactions

Autoimmune disease


Reactive hemophagocytic syndrome


Antiphospholipid antibody syndrome


Transplant rejection


Graft versus host disease


Iatrogenic causes

Delayed or missed injury


Blood transfusion


Injurious mechanical ventilation


Treatment-associated increased intra-abdominal pressure


Intoxication

Drug reactions (anticonvulsants, carboplatin, antiretrovirals, colchicines, propofol, amiodarone, monoclonal antibodies)


Arsenic


Drug intoxication (ecstasy, cocaine, salicylates, acetaminophen)


Endocrine

Adrenal crisis


Pheochromocytoma


Thyroid storm


Myxedema coma


Reproduced from Mizock BA. The multiple organ dysfunction syndrome. Dis Mon 2009;55:476-526.


2. Innate immune cell members consist of neutrophils, macrophages, monocytes, basophils, eosinophils, natural killer cells, mast cells, dendritic cells, and platelets.

3. Pathogen-inducing components capable of triggering an immune response are numerous and include lipopolysaccharide (LPS) from gram-negative bacteria; lipoteichoic acid from gram-positive bacteria, and flagellin.

C. Toll-like receptors (TLRs).

1. TLRs are cell membrane proteins that exist to specifically recognize a variety of pathogen- and tissue damage-associated components.


2. TLRs are a key element to initiating the immune response. TLRs along with other proteins comprise a cadre known as pattern recognition receptors (PRRs).

3. Activation of TLRs leads to initiation of the inflammatory cascade. This includes activation of the critical transcription factor NF-κB. Ongoing response is variable and host dependent.

4. Key TLRs include TLR-2 and TLR-4.

D. Mediators of sepsis.

1. Activation of the inflammatory cascade precipitates the release and interaction of myriad important mediators.

2. These mediators encompass cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α(TNF-α).

3. High mobility group box-1 (HMGB-1) is a unique cytokine that can provoke a lethal proinflammatory response.

4. Additional mediators include platelet-activating factor (PAF), bradykinin, nitric oxide, and elements of the complement system.

E. End-organ consequences.

1. Sepsis-associated mediators contribute to end-organ damage. Damage elements include vasodilatation and altered perfusion, microvascular permeability and thrombosis, myocardial depression, mitochondrial dysfunction, maladaptive use of cellular nutrients, and cellular apoptosis.

III. DIAGNOSIS

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Jun 11, 2016 | Posted by in CRITICAL CARE | Comments Off on Sepsis and Multiorgan Failure

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