sepsis and septic shock

Question 1

bacteremia

Answer 1

(fungemia) - presence of viable bacteria (fungi) in the blood

Question 2

infection

Answer 2

inflammatory response to invasion of normally sterile host tissue by the microorganisms

Question 3

systemic inflammatory response syndrome (SIRS)

Answer 3

systemic inflammatory response to a variety of severe clinical insults (infectious or non-infectious), manifested by 2 or more of the following conditions:
-Temperature > 38°C (> 100.4°F) or under 36°C (under 96.8°F)
-Heart rate > 90 beats/minute
-Respiratory rate > 20 breaths/minute or PaCO2 under 32 mmHg
-WBC count > 12,000/mm3
, under 4,000/mm3
, or > 10% immature (band) forms

Question 4

sepsis

Answer 4

same as SIRS with evidence of infection
Altered mental status
Positive fluid balance (> 20 ml/kg over 24 hours)
Hyperglycemia (> 140 mg/dl in absence of diabetes)
Plasma C-reactive protein/procalcitonin > 2 SD above normal value
Arterial hypotension (SBP under 90 mmHg, MAP under 70 mmHg, or SBP decrease > 40 mmHg in adults)
Cardiac index > 3.5 L/min
Arterial hypoxemia (PaO2/FiO2 under 300)
Acute oliguria (UOP under 0.5 ml/kg/h or 45 ml/h for at least 2 h)
Serum creatinine increase > 0.5 mg/dl
Coagulation abnormalities (INR > 1.5 or aPTT > 60 seconds)
Paralytic ileus (absence of bowel sounds)
Platelets under 100,000/mm3
Bilirubin > 4 mg/dl
Hyperlactatemia (> 1 mmol/L)
Decreased capillary refill

Question 5

severe sepsis

Answer 5

sepsis associated with organ dysfunction, hypoperfusion, or hypotension. Hypoperfusion may include, but not limited to, arterial hypoxemia, lactic acidosis, oliguria, coagulation abnormalities, elevated bilirubin, or an acute alteration in mental status.

Question 6

septic shock

Answer 6

sepsis with persistent hypotension despite adequate fluid resuscitation (IV fluids of 30 ml/kg) or hyperlactatemia.

Question 7

refractory septic shock

Answer 7

persistent septic shock requiring dopamine > 15 mcg/kg/min or norepinephrine > 0.25 mcg/kg/min to maintain mean arterial BP

Question 8

multiple organ dysfunction syndrome

Answer 8

presence of altered organ function in an acutely ill patient so that homeostasis cannot be maintained without intervention

Question 9

epidemiology

Answer 9

Sepsis – ≈ 2% of all hospital admissions; 6-30% of patients in an ICU.
From 1979-2000, incidence of sepsis increased 8.7% per year in hospitalized patients; sepsis rates doubled from 2000 to 2008; ≈ 1 million cases/year
11th leading cause of death in U.S. in 2010; most expensive condition treated in hospitals in 2011; mortality 15-40%
Factors leading to increased incidence of sepsis
-Immunocompromised patients
-More frequent use of invasive devices or procedures
-Greater availability of life-sustaining technology
-Higher frequency of infections caused by antibiotic-resistant organisms
-Aging population with serious underlying conditions

Question 10

causative gram negative bacteria

Answer 10

40% of sepsis cases (50-60% of septic shock cases)
Enterobacteriaceae (E. coli, Klebsiella, Enterobacter, Serratia, Proteus)
Enteric gram-negative bacteria – normal endogenous flora within the GI tract
Integrity of GI mucosa – mechanical barrier (trauma, penetrating wounds, ulcerations, mechanical obstruction, ischemia)
P. aeruginosa** – mechanical ventilation, prolonged hospitalization, burn injury
Acinetobacter baumannii – associated with prior antibiotic exposure

Question 11

causative gram-positive bacteria

Answer 11

40-50% of sepsis cases (25% of septic shock cases)
Staphylococci – associated intravascular devices, artificial heart valves
S. pneumoniae
Enterococci – prolonged hospitalization; treatment with cephalosporins

Question 12

causative fungi

Answer 12

C. albicans – most common (46%)
C. glabrata (26%), C. parapsilosis (16%) C. tropicalis (8%), C. krusei (2.5%) – increasing prevalence
Risk factors: abdominal surgery, poorly controlled diabetes mellitus, prolonged neutropenia, broad-spectrum antibiotics, corticosteroid therapy, prolonged hospitalization, central venous catheter, total parenteral nutrition, hematologic malignancy; chronic indwelling Foley (bladder) catheter

Question 13

microbial pathogenesis

Answer 13

Endotoxin
-Lipopolysaccharide (LPS) component of outer membrane of gram-negative bacilli**
-Activates macrophages and initiates cascade of events which include the release of inflammatory mediators (cytokines, prostaglandins, leukotrienes)
-Pro-inflammatory mediators: tumor necrosis factor α (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 8 (IL-8), platelet-activating factor (PAF), thromboxane A2
-Antiinflammatory mediators: IL-1 receptor antagonist, interleukin 4 (IL-4), interleukin 10 (IL-10)
Peptidoglycan (gram-positive bacteria) – exhibits proinflammatory activity

Question 14

pathophysiology

Answer 14

can be septic w/o bacteremia

blood borne infection - cell wall components toxins - TNF - coagulation OR complement activation

Question 15

diagnostic criteria for sepsis - general variables

Answer 15

Fever (> 38.3°C) or hypothermia (core temperature under 36°C)
Heart rate > 90 bpm or more than 2 standard deviations above the normal range for age)
Tachypnea
Altered mental status
Significant edema or positive fluid balance (> 20 mL/kg over 24 hours)
Hyperglycemia (plasma glucose > 140 mg/dl) in the absence of diabetes

Question 16

diagnostic criteria - inflammatory variables ***

Answer 16

Leukocytosis (WBC > 12,000/mm3)
Leukopenia (WBC under 4,000/mm3)
Normal WBC count with > 10% immature forms
Plasma C-reactive protein more than 2 SD above normal value
Plasma calcitonin more than 2 SD above normal value
-Released when macrophages exposed to bacteria or endotoxin (not viruses)
-PCT increases 3-12 h after stimulation; decline over 24-72 h
-Levels correlate to bacterial load, severity of infection, and mortality
-Greater survival in patients with procalcitonin under 7 ng/mL (39.5%) compared
to ≥ 7 ng/mL (69.1%)
-Decrease in PCT by ≥ 80% over 72 h correlated ICU and in-hospital mortality
-Guidelines for starting antibiotics based on PCT concentration**
—under 0.25 ng/mL – antibiotics strongly discouraged
—≥ 0.25 and under 0.5 ng/mL – antibiotics discouraged
—≥ 0.5 and under 1 ng/mL – antibiotics encouraged
—≥ 1 ng/mL – antibiotics strongly** encouraged

Question 17

diagnostic criteria - hemodynamic variables

Answer 17

arterial hypotension (SBP under 90 mm Hg, MAP under 70 mm Hg, or an SBP decrease > 40 mm Hg in adults

Question 18

diagnostic criteria - organ dysfunction variables

Answer 18

Arterial hypoxemia (PaO2/FIO2 uner 300)
Acute oliguria (urine output under 0.5 mL/kg/hour for at least 2 hours despite adequate fluid resuscitation)
Serum creatinine increase > 0.5 mg/dl
Coagulation abnormalities (INR 1.5 or aPTT > 60 sec)
Ileus (absent bowel sounds)
Thrombocytopenia (platelet count under 100,000/mm3)
Hyperbilirubinemia (total bilirubin > 4 mg/dl)

Question 19

diagnostic criteria - tissue perfusion variables

Answer 19

Hyperlactactemia (> 1 mmol/L)

Decreased capillary refill

Question 20

laboratory studies

Answer 20

Microbiologic investigations
-Blood cultures – at least 2 sets (aerobic & anaerobic) obtained percutaneously and through each vascular access device
-Specimens for direct examination and culture from any primary or metastatic site of infection
-Obtain before antimicrobial therapy if no significant delay (> 45 min) in start of therapy
WBC with differential
Coagulation tests – prothrombin time, partial thromboplastin time, fibrinogen; fibrin degradation (split) products
Tests reflecting organ dysfunction – arterial blood gas, Scr, BUN, LFTs, etc.
Imaging studies – confirm potential source of infection

Question 21

principles of therapy

Answer 21

Early diagnosis and identification of the pathogen
Rapidly eliminate source of infection (e.g., removal of foreign bodies [IV catheters], drain abscesses, debride skin/soft tissue)
Comprehensive supportive care (hemodynamic monitoring, fluid resuscitation, pressor and metabolic support)
Early initiation (within first hour) of aggressive** antimicrobial therapy – 1 or more drugs with in vitro activity against the most likely** pathogens and that penetrates to the site presumed to be the source of sepsis.
Maintain tissue perfusion (decrease organ failure)

Question 22

complete in the first 3 hours* of presentation

Answer 22

Measure lactate concentration
Obtain blood cultures prior to administration of antibiotics
Administer broad spectrum antibiotics
Administer 30 mL/kg crystalloid (NS, LR) for hypotension or lactate ≥ 4 mmol/L

Question 23

complete in the first 6 hours* of presentation

Answer 23

Apply vasopressors (for hypotension not responding to initial fluid resuscitation) to maintain MAP ≥ 65 mmHg
In event of persistent hypotension after initial fluid administration (MAP < 65 mmHg) or if initial lactate was ≥ 4 mmol/L, re-assess volume status and tissue perfusion (document findings)
Re-measure lactate if initial lactate was elevated

Question 24

document reassessment of volume status and tissue perfusion with:

Answer 24

Repeat focused exam (after initial fluid resuscitation) including vital signs, capillary refill, cardiopulmonary, pulse, skin findings
Or two of the following: measure CVP; measure ScvO2; bedside ultrasound; dynamic assessment with passive leg raise or fluid challenge

Question 25

initial resuscitation

Answer 25

Goals in the first 3 hours: CVP 8-12 mm Hg; MAP ≥ 65 mm Hg; urine output ≥ 0.5 mL/kg/hour; central venous O2 saturation 70%
Normalize lactate in patients with elevated lactate concentrations
Crystalloids (normal saline, lactated Ringer’s) – initial fluid of choice in severe sepsis and septic shock

Question 26

antimicrobial therapy

Answer 26

Prompt initiation (within first hour) of empiric, broad-spectrum, IV antibiotics to provide coverage for all likely pathogens in the context of the clinical setting (broad-spectrum)
-What is the suspected site of infection?
-What are the most likely pathogens?
-Are pathogens from the community vs. hospital vs. nursing home?
-What is the patient’s immune status
-What is the susceptibility or resistance profile for the institution?
Antimicrobial selection should be modified based on culture and susceptibility results (de-escalation)
Combination therapy is usually recommended for polymicrobial infections, prevents development of resistance, and may result in synergy, especially for Pseudomonas, enterococci, and for infections in neutropenic patients

Question 27

suggested antimicrobial regimens for empiric therapy of community-acquired sepsis in non-neutropenic patients**

Answer 27

Community-acquired pneumonia
-Ceftriaxone + azithromycin
-Ceftriaxone + respiratory fluoroquinolone (moxifloxacin, levofloxacin)
Suspected urinary tract source
-3rd or 4th generation cephalosporin (± aminoglycoside)
-Piperacillin/tazobactam (± aminoglycoside)
-Fluoroquinolone (ciprofloxacin or levofloxacin) – concern for resistance
Suspected intra-abdominal source
-Piperacillin/tazobactam
-Carbapenem
-3rd or 4th generation cephalosporin + metronidazole
-Ciprofloxacin or levofloxacin + metronidazole
Suspected skin and soft-tissue infection (cellulitis)
-Vancomycin
-Linezolid
-Daptomycin

Question 28

suggested antimicrobial empiric regimens of hospitla-acquired non-neutropenic sepsis***

Answer 28

Suspected pneumonia (HAP, VAP)
-Antipseudomonal β-lactam + aminoglycoside or antipseudomonal fluoroquinolone + vancomycin or linezolid
Suspected urinary tract source (? P. aeruginosa)
-Cefepime + aminoglycoside (tobramycin) or FQ (not moxi)
-Piperacillin/tazobactam + aminoglycoside (tobramycin) or FQ (not moxi)
Suspected intra-abdominal source
-Piperacillin/tazobactam ± aminoglycoside
-Carbapenem (not ertapenem) ± aminoglycoside
Suspected skin and soft-tissue infection (cellulitis, necrotizing fasciitis)
-Vancomycin + piperacillin/tazobactam (+ clindamycin if necrotizing
fasciitis)

Question 29

suggested antimicrobial therapy in hospital-acquired infection of a neutropenic patient

Answer 29

Piperacillin/tazobactam ± aminoglycoside
Antipseudomonal carbapenem ± aminoglycoside
Ceftazidime or cefepime ± aminoglycoside

Question 30

suggested antimicrobial therapy in sepsis and thermal injury to at least 20% of the BSA*

Answer 30

Antipseudomonal β-lactam + aminoglycoside + vancomycin

Question 31

suggested antimicrobial therapy in sepsis with suspicion of indwelling vascular catheter infection

Answer 31

Vancomycin ± aminoglycoside
Daptomycin
Linezolid

Question 32

duration of therapy

Answer 32

7-10 days (longer if slow clinical response, undrainable source of infection, S. aureus bacteremia, certain viral or fungal infections, neutropenia)

Question 33

guidelines for continuing* or stopping* antibiotics based on PCT concentration***

Answer 33

less than 0.25 ng/mL – stopping antibiotics strongly** encouraged
80% decrease from peak concentration or ≥ 0.25 and < 0.5 ng/mL – stopping antibiotics encouraged
less than 80% decrease from peak concentration or ≥ 0.5 ng/mL – continuing antibiotics encouraged
Increase concentration compared to peak and ≥ 0.5 ng/mL – changing antibiotics strongly*** encouraged