MODS results from progressive physiologic failure of two or more separate organ systems in an acutely ill patient such that homeostasis cannot be maintained without intervention.86 MODS is the major cause of death in patients cared for in
FIG 26-7 Evaluation for Severe Sepsis Screening Tool. (Redrawn from the Institute for Health-care Improvement, Cambridge, MA. Copyright 2005 Surviving Sepsis Campaign and the Institute for Healthcare Improvement.)
Instructions: Use this optional tool to screen patients for severe sepsis in the emergency department, on the wards, or in the ICU.
1. Is the patient’s history suggestive of a new infection?
Pneumonia, empyema Urinary tract infection Acute abdominal infection Meningitis
Skin/soft tissue infection
Bone/joint infection Wound infection Bloodstream catheter infection
Endocarditis
Implantable device infection
Other ____________
___ Yes ___ No 2. Are any two of the following signs & symptoms of infection both present and new to the patient? Note:
laboratory values may have been obtained for inpatients but may not be available for outpatients.
If the answer is yes to both either question 1 and 2, suspicion of infection is present:
Hyperthermia 38.3° C (101.0° F)
Hypothermia 36° C (96.8° F)
Tachycardia 90 bpm
Obtain: lactic acid, blood cultures, CBC with differential, basic chemistry labs, bilirubin.
At the physician’s discretion obtain: UA, chest x-ray, amylase, lipase, ABG, CRP, CT scan.
Tachypnea 20 bpm Acutely altered mental status
Leukocytosis (WBC count
12,000 mcg-1)
Leukopenia (WBC count
4000 mcg-1) Hyperglycemia (plasma glucose 120 mg/dL) in the absence of diabetes ___ Yes ___ No
3.
If suspicion of infection is present AND organ dysfunction is present, the patient meets the criteria for SEVERE SEPSIS and should be entered into the severe sepsis protocol.
Are any of the following organ dysfunction criteria present at a site remote from the site of the infection that are not considered to be chronic conditions? Note: the remote site stipulation is waived in the case of bilateral pulmonary infiltrates.
SBP 90 mm Hg or MAP 65 mm Hg SBP decrease 40 mm Hg from baseline
Bilateral pulmonary infiltrates with a new (or increased) oxygen requirement to maintain SpO2 90%
Bilateral pulmonary inflitrates with PaO2/FiO2 ratio 300
Creatinine 2.0 mg/dL (176.8 mmol/L) or Urine Output 0.5 mL/kg/hour for 2 hours Bilirubin 2 mg/dL (34.2 mmol/L)
Platelet count 100,000
Coagulopathy (INR 1.5 or aPTT 60 secs) Lactate 2 mmol/L (18.0 mg/dL)
Date: ___/___/___ (circle: dd/mm/yy or mm/dd/yy) Version 7.12.2005
Time: ___:___ (24 hr. clock)
© 2005 Surviving Sepsis Campaign and the Institute for Healthcare Improvement ___ Yes ___ No
Evaluation for Severe Sepsis Screening Tool
Trauma patients are particularly vulnerable to developing MODS because they often experience ischemia-reperfusion events resulting from hemorrhage, blunt trauma, or SNS-induced vasoconstriction.125 Other high-risk patients include those who have experienced infection, a shock episode, various ischemia-reperfusion events, acute pancreatitis, sepsis, burns, aspiration, multiple blood transfusions, or sur-gical complications.86 Patients age 65 years or older are at increased risk because of their decreased organ reserve and comorbidities.126
Organ dysfunction may be the direct consequence of an initial insult (Primary MODS) or can manifest latently and involve organs not directly affected in the initial insult (Secondary MODS). Patients can experience both Primary and Secondary MODS (Figure 26-8).
Primary MODS results from a well-defined insult in which organ dysfunction occurs early and is directly attributed to the insult itself. Direct insults initially cause localized BOX 26-19 NURSING DIAGNOSIS
PRIORITIES
• Deficient Fluid Volume related to relative loss, p. 584
• Decreased Cardiac Output related to alterations in preload, p. 579
• Decreased Cardiac Output related to alterations in contrac-tility, p. 580
• Impaired Gas Exchange related to ventilation/perfusion mismatching or intrapulmonary shunting, p. 594
• Imbalanced Nutrition: Less Than Body Requirements related to increased metabolic demands or lack of exoge-nous nutrients, p. 593
• Anxiety related to threat to biologic, psychologic, or social integrity, p. 576
Septic Shock
A. Initial Resuscitation
1. Protocolized, quantitative resuscitation of patients with sepsis-induced tissue hypoperfusion. Goals during first 6 hrs of resuscitation:
a) Central venous pressure 8-12 mm Hg b) Mean arterial pressure (MAP) ≥ 65 mm Hg c) Urine output ≥ 0.5 mL/kg/hr
d) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively (grade 1C).
2. In patients with elevated lactate levels, targeting resus-citation to normalize lactate (grade 2C).
B. Screening for Sepsis and Performance Improvement 1. Routine screening of potentially infected seriously ill
patients for severe sepsis to allow earlier implementation of therapy (grade 1C).
2. Hospital–based performance improvement efforts in severe sepsis (UG).
C. Diagnosis
1. Cultures before antimicrobial therapy if delay is <45 min in the start of antimicrobial(s) (grade 1C). ≥2 sets of blood cultures (aerobic and anaerobic) with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was inserted <48 hrs (grade 1C).
2. 1,3 beta-D-glucan assay (grade 2B), mannan and anti-mannan antibody assays (2C), if available and invasive candidiasis is in differential diagnosis.
3. Imaging studies to confirm a potential source of infection (UG).
D. Antimicrobial Therapy
1. Goal: IV antimicrobials within first hour of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C).
2a. Initial empiric antiinfective therapy of drug(s) active against all likely pathogens and that penetrate inade-quately into sepsis source tissues (grade 1B).
2b. Antimicrobial regimen reassessed daily for potential deescalation (grade 1B).
3. Low procalcitonin levels or similar biomarkers assist clinicians in discontinuation of therapy in patients who initially appeared septic, but have no subsequent evi-dence of infection (grade 2C).
4a. Combination therapy for neutropenic patients with severe sepsis (grade 2B) and for patients with difficult-to-treat, multi-drug-resistant bacterial pathogens (grade 2B). For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone (for P. aeruginosa bacteremia) (grade 2B). A combination of beta-lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections (grade 2B).
4b. Combination therapy should not be administered for
>3-5 days. Deescalation to most appropriate single therapy should be performed as soon as the suscepti-bility profile is known (grade 2B).
5. Duration of therapy typically 7-10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S. aureus, and some fungal and viral infections or immunologic deficiencies (grade 2C).
6. Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin (grade 2C).
7. Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause (UG).
E. Source Control
1. Specific anatomical diagnosis and emergent source control should be diagnosed or excluded as rapidly as possible; source control intervention should be under-taken <12 hr after diagnosis, if feasible (grade 1C).
2. When source is potentially infected peripancreatic necro-sis, definitive intervention is best delayed until after adequate demarcation of viable tissues (grade 2B).
BOX 26-20 EVIDENCE-BASED PRACTICE QSEN Severe Sepsis and Septic Shock Management Guidelines
BOX 26-20 EVIDENCE-BASED PRACTICE—cont’d Severe Sepsis and Septic Shock Management Guidelines
3. For source control in severely septic patients, effective interventions associated with the least physiologic insult should be used (UG).
4. If IV access devices are possible sources, they should be removed promptly after other vascular access has been established (UG).
F. Infection Prevention
1a. Selective oral and digestive decontamination should be considered to reduce the incidence of ventilator-associated pneumonia; this can be instituted in settings where it is effective (grade 2B).
1b. Oral chlorhexidine gluconate should be used to reduce risk of ventilator-associated pneumonia in ICU patients with severe sepsis (grade 2B).
G. Fluid Therapy of Severe Sepsis
1. Crystalloids initially in resuscitation of severe sepsis and septic shock (grade 1B).
2. Against hydroxyethyl starches for resuscitation of severe sepsis and septic shock (grade 1B).
3. Albumin in resuscitation of severe sepsis and septic shock when patients require substantial crystalloids (grade 2C).
4. Initial fluid challenge (to a minimum of 30 mL/kg of crystalloids) in patients with sepsis-induced tissue hypo-perfusion with suspicion of hypovolemia. More rapid administration and greater amounts may be needed in some (grade 1C).
5. Fluid challenge technique may be applied wherein fluid administration is continued if there is hemodynamic improvement based on dynamic or static variables (UG).
H. Vasopressors
1. Vasopressor therapy initially to target mean arterial pres-sure (MAP) of 65 mm Hg (grade 1C).
2. Norepinephrine (NE) as first choice vasopressor (grade 1B).
3. Epinephrine (added to and potentially substituted for nor-epinephrine) when additional agent is needed to maintain adequate BP (grade 2B).
4. Vasopressin 0.03 units/minute can be added to NE to raise MAP or decrease NE dosage (UG).
5. Low-dose vasopressin not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension. Vasopressin doses >0.03-0.04 units/minute should be reserved for salvage therapy (UG).
6. Dopamine as an alternative to norepinephrine only in highly selected patients (grade 2C).
7. Phenylephrine not recommended in the treatment of septic shock except where a) norepinephrine is associated with serious arrhythmias, b) cardiac output is high and BP persistently low, or c) as salvage therapy when combined inotrope/vasopressor drugs and low-dose vasopressin have failed to achieve MAP target (grade 1C).
8. Low-dose dopamine should not be used for renal protec-tion (grade 1A).
9. All patients requiring vasopressors have an arterial cath-eter placed as soon as practical (UG).
I. Inotropic Therapy
1. A trial of dobutamine infusion up to 20 mcg/kg/min be administered or added to vasopressor (if in use) in the presence of a) myocardial dysfunction or b) ongoing signs of hypoperfusion, despite adequate intravascular volume and adequate MAP (grade 1C).
2. Not using a strategy to increase cardiac index to prede-termined supranormal levels (grade 1B).
J. Corticosteroids
1. Do not use IV hydrocortisone to treat adults if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability. Otherwise, IV hydrocorti-sone alone at a dose of 200 mg per day (grade 2C) is suggested.
2. Do not use ACTH stimulation test to identify adults who should receive hydrocortisone (grade 2B).
3. If used, hydrocortisone tapered when vasopressors no longer required (grade 2D).
4. Do not use corticosteroids for treatment of sepsis without shock (grade 1D).
5. When hydrocortisone is given, use continuous flow (grade 2D).
K. Blood Product Administration
1. Once tissue hypoperfusion has resolved (in absence of extenuating circumstances), red blood cell transfusion is recommended only when Hgb decreases to <7.0 g/dL to target an Hgb concentration of 7.0-9.0 g/dL in adults (grade 1B).
2. Do not use erythropoietin to treat anemia associated with severe sepsis (grade 1B).
3. Do not use fresh frozen plasma to correct laboratory clot-ting abnormalities in the absence of bleeding or planned invasive procedures (grade 2D).
4. Do not use antithrombin for treatment of severe sepsis and septic shock (grade 1B).
5. In patients with severe sepsis, administer platelets pro-phylactically when <10,000/mm3 (10 × 109/L) in absence of apparent bleeding. Prophylactic platelet transfusion suggested when <20,000/mm3 (20 × 109/L) if patient has significant risk of bleeding. Higher platelet counts (≥50,000/mm3 [50 × 109/L]) advised for active bleeding, surgery, or invasive procedures (grade 2D).
L. Immunoglobulins
1. Do not use IV immunoglobulins in adults with severe sepsis or septic shock (grade 2B).
M. Selenium
1. Do not use IV selenium for treatment of severe sepsis (grade 2C).
N. Mechanical Ventilation of Sepsis-Induced Acute Respi-ratory Distress Syndrome (ARDS)
1. Target tidal volume of 6 mL/kg predicted body weight in patients with sepsis-induced ARDS (grade 1A vs.
12 mL/kg).
2. Measure plateau pressures in patients with ARDS.
Initial upper limit goal in a passively inflated lung is
≤30 cm H2O (grade 1B).
3. Apply positive end-expiratory pressure (PEEP) to avoid alveolar collapse at end expiration (grade 1B).
Continued
4. Use strategies based on higher levels of PEEP for patients with sepsis-induced moderate or severe ARDS (grade 2C).
5. Use recruitment maneuvers in sepsis patients with severe refractory hypoxemia (grade 2C).
6. Use prone positioning in sepsis-induced ARDS patients with a PaO2/FiO2 ratio ≤100 mm Hg (grade 2B).
7. Maintain mechanically ventilated sepsis patients with head of bed elevated 30-45° to limit aspiration risk and prevent development of ventilator-associated pneumo-nia (grade 1B).
8. Use noninvasive mask ventilation (NIV) in that minority of sepsis-induced ARDS patients in whom the benefits of NIV have been carefully considered (grade 2B).
9. Put a weaning protocol in place. Mechanically ventilated patients with severe sepsis should undergo spontane-ous breathing trials regularly to evaluate ability to discontinue mechanical ventilation when they a) are arousable, b) are hemodynamically stable (without vaso-pressor agents), c) have no new potentially serious conditions, d) have low ventilator and end-expiratory pressure requirements, and e) have low FiO2 require-ments that can be met with a face mask or nasal cannula. If spontaneous breathing trial is successful, consider extubation (grade 1A).
10. Do not routinely use pulmonary artery catheter for patients with sepsis-induced ARDS (grade 1A).
11. Use a conservative fluid strategy for patients with established sepsis-induced ARDS who do not have evi-dence of tissue hypoperfusion (grade 1C).
12. In the absence of specific indications, do not use beta 2-agonists for treatment of sepsis-induced ARDS (grade 1B).
O. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis
1. Continuous or intermittent sedation should be minimized in mechanically ventilated sepsis patients, targeting spe-cific titration endpoints (grade 1B).
2. Avoid neuromuscular blocking agents (NMBAs) if possi-ble in septic patients without ARDS due to risk of pro-longed neuromuscular blockade following discontinuation.
If NMBAs must be maintained, use either intermittent bolus as required or continuous infusion with train-of-four monitoring (grade 1C).
3. Use a short course of NMBA ≤48 hours for patients with early sepsis-induced ARDS and PaO2/FiO2< 150 mm Hg (grade 2C).
P. Glucose Control
1. A protocolized approach to management in ICU patients with severe sepsis commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dL.
Approach should target an upper blood glucose ≤180 mg/
dL (grade 1A).
2. Blood glucose values should be monitored every 1-2 hrs until glucose values and insulin infusion rates stabilize, then every 4 hr, thereafter (grade 1C).
3. Glucose levels obtained with point-of-care testing of cap-illary blood should be interpreted with caution (UG).
Q. Renal Replacement Therapy
1. Continuous renal replacement therapies and intermittent hemodialysis are equivalent in severe sepsis and acute renal failure (grade 2B).
2. Use continuous therapies to facilitate management of fluid balance in hemodynamically unstable septic patients (grade 2D).
R. Bicarbonate Therapy
1. Do not use sodium bicarbonate therapy for improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥7.15 (grade 2B).
S. Deep Vein Thrombosis Prophylaxis
1. Patients with severe sepsis should receive daily pharma-coprophylaxis against venous thromboembolism (grade 1B). Accomplish with daily subcutaneous low–molecular- weight heparin (LMWH) (grade 1B vs. twice daily UFH, grade 2C vs. three times daily UFH). If creatinine clear-ance <30 mL/min, use dalteparin (grade 1A) or another form of LMWH that has a low degree of renal metabo-lism (grade 2C) or UFH (grade 1A).
2. Treat patients with severe sepsis with combination of pharmacologic therapy and intermittent pneumatic com-pression devices if possible (grade 2C).
3. Do not use pharmacoprophylaxis in septic patients who have a contraindication for heparin use (grade 1B).
Use mechanical prophylactic treatment (grade 2C), unless contraindicated. When risk decreases, start phar-macoprophylaxis (grade 2C).
T. Stress Ulcer Prophylaxis
1. Give stress ulcer prophylaxis using H2 blocker or proton pump inhibitor to patients with severe sepsis/septic shock who have bleeding risk factors (grade 1B).
2. If used, proton pump inhibitors preferred over H2RA (grade 2D)
3. Patients without risk factors do not receive prophylaxis (grade 2B).
U. Nutrition
1. Administer oral or enteral feedings rather than either complete fasting or provision of only IV glucose within the first 48 hours after diagnosis of severe sepsis/septic shock (grade 2C).
2. Avoid mandatory full caloric feeding in first week. Suggest low-dose feeding, advancing only as tolerated (grade 2B).
3. Use IV glucose and enteral nutrition rather than total parenteral nutrition alone or parenteral nutrition in con-junction with enteral feeding in the first 7 days after diagnosis of severe sepsis/septic shock (grade 2B).
4. Use nutrition with no specific immunomodulating supple-mentation in patients with severe sepsis (grade 2C).
V. Setting Goals of Care
1. Discuss goals and prognosis with patients and families (grade 1B).
2. Incorporate goals into treatment and end-of-life care plan-ning (grade 1B).
3. Address goals as early as feasible, but no later than within 72 hours of ICU admission (grade 2C).
Data from Dellinger RP, Levy MM, 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.
UG, Ungraded.
FIG 26-8 Pathogenesis of Multiple Organ Dysfunction Syndrome. GI, Gastrointestinal;
MDF, myocardial depressant factor; MODS, multiple organ dysfunction syndrome; PAF, platelet activating factor; WBCs, white blood cells. (From McCance KL, Huether SE, eds. Pathophysiol-ogy: The Biological Basis for Disease in Adults and Children. 7th ed. St. Louis: Elsevier; 2014.) Initial organ
injury
Activation of resident macrophages/neutrophils
Local/mild systemic inflammatory/stress response
PRIMARY MODS
Postinjury insult Primed inflammatory system
Endothelial dysfunction Neuroendocrine response
Activation of complement, coagulation, kallikrein/kinin, and fibrinolytic cascades
Microvascular clotting Neutrophil adherence and activation
Macrophage activation
GI microcirculatory failure
Impaired microvascular circulation
PAF O2 radicals
Proteases Eicosanoids
Eicosanoids O2 radicals Proteases Cytokines
Gut barrier failure
Systemic endotoxemia
Hypermetabolism Hyperdynamic circulation Uncontrolled systemic
inflammatory/stress response Vasodilation
↑ Capillary permeability Selective vasoconstriction
Endothelial damage
Maldistribution of blood flow
Interstitial edema
Recruitment of additional WBCs
Myocardial depression Impaired tissue
perfusion
O2 supply/demand imbalance
↑ O2 and substrate demand
Myocardial dysfunction Supply-dependent O2 consumption
MDF Tissue hypoxia
Acidosis Impaired cellular function
SECONDARY MODS
Exhaustion of fuel supply Mitochondrial
dysfunction
Metabolic failure
Clinical Conditions
• Infection
• Infection of vascular structures (heart and lungs)
• Pancreatitis
• Tissue ischemia or hypoxia
• Multiple trauma with massive tissue injury
• Hemorrhagic shock
• Immune-mediated organ injury
• Exogenous administration of tumor necrosis factor or other cytokines
• Aspiration of gastric contents
• Massive transfusion
• Host defense abnormalities Clinical Manifestations
• Temperature >38° C or <36° C
• Heart rate >90 beats/min
• Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg
• WBC >12,000 cells/mm3 or <4000 cells/mm3 or >10%
immature (band) forms
BOX 26-21 Clinical Conditions and Manifestations Associated with SIRS
WBC, White blood cell count.
inflammatory responses. Primary MODS accounts for only a small percentage of MODS cases. Examples of Primary MODS include the immediate consequences of posttraumatic pulmonary failure, thermal injuries, AKI, or invasive infec-tions.86 These cellular or microcirculatory insults may lead to a loss of critical organ function induced by failure of delivery of oxygen and substrates, coupled with the inability to remove end-products of metabolism. The inflammatory response in Primary MODS has a less apparent presentation and may resolve without long-term implications. However, Primary MODS may “prime” physiologic systems for a more sustained exaggerated inflammatory response that leads to Secondary MODS.
Secondary MODS is a consequence of widespread sus-tained systemic inflammation that results in dysfunction of organs not involved in the initial insult. Secondary MODS develops latently after an initial insult.86 The early impairment of organs normally involved in immunoregulatory function, such as the liver and the GI tract, intensifies the host response to the insult.127 The initial insult may prime the inflammatory system in such a way that even a mild second insult (hit) may perpetuate a sustained hyperinflammatory response. This
“two-hit hypothesis” has been increasingly recognized as an important contributor to morbidity and mortality in patients with Secondary MODS.128
SIRS and sepsis are common initiating events in the devel-opment of Secondary MODS. The systemic inflammatory response is an intense host response characterized by sus-tained generalized inflammation in organs remote from the initial insult. SIRS is widespread inflammation or clinical responses to inflammation that occur in patients suffering a variety of insults. Clinical conditions and manifestations associated with SIRS are listed in Box 26-21. These insults produce similar or identical systemic inflammatory responses, even in the absence of infection. The diagnostic criteria for
SIRS have been previously addressed (Figure 26-7). Manifes-tations of SIRS must represent an acute alteration from the patient’s normal baseline and must not be related to other causes (e.g., neutropenia from chemotherapy). Organ dys-function, such as ARDS, AKI, and MODS, is a complication of SIRS.86,123 In epidemiologic studies, SIRS was found to occur in one-third of all hospitalized patients, in 50% to 93%
of all patients in critical care units, and in about 80% of all patients in surgical critical care units.129-130
When SIRS is a result of infection, the term sepsis is used.
SIRS, sepsis, severe sepsis, and septic shock represent a hier-archical continuum of the inflammatory response to infec-tion.17 Infection and shock are the most common precipitating factors; however, any disease that induces a major inflamma-tory response can initiate the events that lead to MODS.
When inflammation is not contained locally, consequences occur systemically that lead to organ dysfunction, including intense, uncontrolled activation of inflammatory cells, direct damage of vascular endothelium, disruption of immune cell function, persistent hypermetabolism, and maldistribution of circulatory volume to organ systems. Inflammation becomes a systemic, self-perpetuating process that is inadequately con-trolled and results in organ dysfunction.123
During hypermetabolism, changes occur in cellular ana-bolic and cataDuring hypermetabolism, changes occur in cellular ana-bolic function, resulting in autocatabolism.
Autocatabolism manifests as a severe decrease in lean body mass, severe weight loss, anergy, and increased CO and VO2 resulting from profound alterations in carbohydrate, protein, and fat metabolism.123 Concurrently, GI, hepatic, and immu-nologic dysfunction may occur, which intensifies systemic inflammation.131 Clinical consequences may affect gut func- tion, wound healing, muscles wasting, host response, respira-tory function, and continued promotion of the hypermetabolic response.
Not all patients develop MODS from SIRS. The develop-ment of MODS appears to be associated with failure to control the source of inflammation or infection, persistent hypoperfusion, flow-dependent oxygen consumption (VO2), or the continued presence of necrotic tissue.125
Pathophysiology
Secondary MODS results from altered regulation of the patient’s acute immune and inflammatory responses. Dys-regulation, or failure to control the host inflammatory response, leads to the excessive production of inflammatory cells and biochemical mediators that cause widespread damage to vascular endothelium and organ damage.123,132 The critically ill patient’s compromised immune state also fosters an environment conducive to organ failure.
The definitive clinical course of Secondary MODS has not been completely identified. Organ dysfunction may occur in a sequential or progressive pattern. Organ dysfunction may begin in the lungs, the most commonly affected major organ, and progress to the liver, gut, and kidneys. Cardiac and bone marrow dysfunction may follow. Neurologic and autonomic system impairment may occur and propagate the progression of organ failure and is associated with illness severity and mortality.133 Organs may fail simultaneously; for example, kidney dysfunction may occur concurrently with hepatic dys-function. After the initial insult and resuscitation, patients develop persistent hypermetabolism, a metabolic conse-quence of sustained systemic inflammation and physiologic stress, followed closely by pulmonary dysfunction, mani-fested as ARDS.
translocation, sustained inflammation, endogenous endotox-emia, and MODS.123,132 Hypoperfusion and shocklike states damage the normal gastrointestinal mucosa barrier by decreasing mesenteric blood flow, leading to hypoperfusion of the villi, mucosal edema, ischemic necrosis, sloughing of the mucosa, and malabsorption. The gastrointestinal tract is extremely vulnerable to oxygen metabolite-induced reperfu-sion injury. Endothelial injury and gastrointestinal lesions occur in response to mediator-induced tissue damage. Isch-emic events and the absence of feedings can disrupt the normal metabolism of the gastric or intestinal lumen and the normal protective function of the gut barrier.119,127
The translocation of gastrointestinal bacteria through a
“leaky gut” into the systemic circulation initiates and per-petuates an inflammatory focus in the critically ill patient.127 The gastrointestinal tract harbors organisms that present an inflammatory focus when carried from the gut via the intes-tinal lymphatics. After hemorrhagic shock, trauma, or a major burn injury, gut-released proinflammatory and tissue-injurious factors may lead to acute lung injury, bone marrow failure, myocardial dysfunction, neutrophil activation, RBC injury, and endothelial cell activation and injury. These factors, released from the gut and carried in the mesenteric lymphatics, are capable of causing a septic state and Second-ary MODS. In summary, the “gut-lymph hypothesis” pro-poses that gut ischemia-reperfusion injury leads to loss of a gut-protective barrier, bacterial translocation, and a gut inflammatory response. Gut-derived inflammatory factors are carried in the mesenteric lymph leading to a septic state and distant organ failure and MODS.2
Lastly, the oropharynx of the critically ill patient also becomes colonized with potentially pathogenic organisms from the gastrointestinal tract. Pulmonary aspiration of colo-nized secretions presents an inflammatory focus that can contribute to concomitant pulmonary dysfunction.134 Hepatobiliary Dysfunction
The liver plays a vital role in host homeostasis related to the acute inflammatory response. The liver responds to sus-tained inflammation by selectively altering carbohydrate, fat, and protein metabolism. Consequently, hepatic dysfunction threatens the patient’s survival. The liver normally controls the inflammatory response by several mechanisms. Kupffer cells, which are hepatic macrophages, detoxify substances that may normally induce systemic inflammation and vasoac-tive substances that cause hemodynamic instability. Failure to detoxify gram-negative bacteria causes endotoxemia, perpetuates SIRS, and may lead to MODS. The liver also produces proteins and antiproteases to control the inflam-matory response; however, hepatic dysfunction limits this response.
Common causes of liver failure in critically ill patients are infection-related cholestasis and hepatocellular injury in response to toxins and to toxins themselves. In infection-related cholestasis, bacterial toxins and released cytokines affect the uptake and excretion of bilirubin leading to jaun-dice. In hepatocellular injury, endotoxins and bacteria are phagocytized by Kupffer cells that release hepatotoxic sub-stances that cause cellular damage. Hepatic dysfunction may also occur with organ hypoperfusion, hemolysis, and with hepatotoxic medications. Measurements of liver enzymes, bilirubin, ammonia, and liver-produced proteins should be carefully monitored.135
Certain cellular and biochemical activity evoke the inflam-matory and immune responses implicated in SIRS and MODS. The mediators associated with SIRS and MODS can be classified as inflammatory cells, biochemical mediators, or plasma protein systems (Box 26-22). Activation of one media-tor often leads to activation of another. The biologic activity of inflammatory cells, biochemical mediators, and plasma protein systems and how they work in concert to cause SIRS and MODS have not been totally determined.
Assessment and Diagnosis
Secondary MODS is a systemic disease with organ-specific manifestations. Organ dysfunction is influenced by numer-ous factors, including organ host defense function, response time to the injury, metabolic requirements, organ vasculature response to vasoactive medications, organ sensitivity to damage, and physiologic reserve. The responses of the gastro-intestinal, hepatobiliary, cardiovascular, pulmonary, renal, and hematologic systems are discussed in the following para- graphs. Clinical manifestations of organ dysfunction are out-lined in Box 26-23.
Gastrointestinal Dysfunction
The gastrointestinal tract plays an important role in MODS.
Gastrointestinal organs normally have immunoregulatory functions, and the gastrointestinal tract contains about 70%
to 80% of the immunologic tissue of the entire body. A nor-mally functioning gastrointestinal tract prevents bacteria from entering the systemic circulation.123 Normal gut flora and gut environment are altered in patients with severe SIRS.
Healthy probiotics (e.g., Bifidobacterium, Lacto bacillus) are decreased in a SIRS state, and pathogenic organisms (e.g., Staphylococcus, Pseudomonas) proliferate.131
With microcirculatory failure to the gastrointestinal tract, the gut’s barrier function may be lost, which leads to bacterial
Inflammatory Cells
• Neutrophils
• Macrophages or monocytes
• Mast lymphocytes
• Endothelial
Biochemical Mediators
• Reactive oxygen species
• Superoxide radical
• Hydroxyl radical
• Hydrogen peroxide
• Tumor necrosis factor
• Interleukins
• Platelet activating factor
• Arachidonic acid metabolites
• Prostaglandins
• Leukotrienes
• Thromboxanes
• Proteases
Plasma Protein Systems
• Complement
• Kinin
• Coagulation
BOX 26-22 Inflammatory Mediators