Sepsis

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Contents 1 More Specific Terms 2 Introduction 3 Etiology 4 Pathology 5 Genetics 6 Clinical-manifestations 7 Diagnostic-criteria 8 Laboratory 9 Diagnostic-procedures 10 Radiology 11 Complications 12 Differential-diagnosis 13 Management 14 More General Terms 15 Additional Terms 16 References

More Specific Terms

• pyemia
• septic shock
• urosepsis

Introduction

• The presence of various pus-forming & other pathogenic organisms or their toxins, in the blood or tissues. The same organism is often isolated in both the blood & the primary site of infection. Sepsis has features of systemic inflammatory response syndrome ( SIRS).

Etiology

• gram negative organisms account for 2/3 of positive blood cultures
• gram positive cocci account for 10-20% of positive blood cultures
• fungi account for 5% of positive blood cultures
• Rickettsia ( Rocky Mountain spotted fever)
• malaria

Pathology

• microbial invasion of the blood stream is not essential for the development of sepsis
• microbial endotoxins can lead to systemic symptoms
• myocardial depression due to tumor necrosis factor ( TNF)

• ventricular dilation
• reduced ventricular ejection fraction
• maintenance of stroke volume

Genetics

• CASP12 implicated in susceptibility to severe sepsis

Clinical-manifestations

• fever
• tachycardia
• tachypnea
• hypotension
• delirium
• severe symptoms in septic shock

• ileus
• oliguria
• metabolic acidosis

• cough, dyspnea & sputum production suggest pulmonary source
• dysuria, frequency & flank pain suggest urosepsis
• nausea, vomiting & diarrhea suggest gastroenteritis
• petechiae or purpura associated with Neisseria meningitidis
• petechial lesions associated with Rocky Mountain spotted fever
• generalized erythroderma associated with Staphylococcus aureus or Streptococcus pyogenes
• ecthyma gangrenosum is a cutaneous ulceration associated with Pseudomonas aeruginosa

Diagnostic-criteria

• (Clinical criteria)
• temp > 38 C or < 36 C
• heart rate > 90/min
• respiratory rate > 20/min or paCO2 < 32 torr
• WBC > 12,000 cells/ mm3 or < 4000 cells/ mm3 or > 10% bands
• documented infection

Laboratory

• blood cultures:

• 2 cultures at different sites
• 3 cultures 60 minutes apart
• 6 cultures over 2 days if endocarditis suspected

• sputum cultures
• urinalysis & urine cultures
• complete blood count ( CBC)

• leukocytosis with predominance of neutrophils & band forms with bacteremia
• leukopenia may be present especially in elderly & immunocompromised
• thrombocytopenia with severe sepsis

• chem 7

• serum Na+ ( hyponatremia), serum K+ ( hyperkalemia)
• serum Cl- (calculation of anion gap)
• serum HCO3- may be low consistent with metabolic acidosis
• BUN, serum creatinine to assess oliguria
• serum glucose

• serum lactate

• persistently elevated despite fluid resuscitation in severe sepsis/ septic shock
• predicts mortality about as well as MEDS score

• remove & culture all indwelling catheters
• aspiration of joint if joint infection suspected
• gram stain & culture of wounds
• paracentesis of ascites fluid
• as indicated

• lumbar puncture if intracranial infection is suspected
• serum bilirubin > 4 mg/dL with severe sepsis
• serum ALT, serum AST
• serum amylase
• DIC panel ( PT/PTT, plasma fibrinogen, D-dimer)
• arterial blood gas ( ABG): PaO2/ FiO2 < 300
• serum cortisol ( adrenal insuffiency)
• cosyntropin stimulation test (see Management)

Diagnostic-procedures

• electrocardiogram:

• 12 lead EKG
• cardiac monitor

• echocardiogram for all septic patients

• obtain transthoracic echocardiogram ( TTE)
• if TTE is negative, obtain transesophageal echocardiogram ( TEE) [4]

Radiology

• chest X-ray
• ultrasound or CT of kidneys if complicated urosepsis suspected
• imaging of abdominal contents if indicated

Complications

• septic shock
• stroke (HR=6.0) [9]
• new-onset atrial fibrillation

• associated with increased mortality (HR-1.5) [9]

Differential-diagnosis

• anaphylaxis
• drug overdose
• pancreatitis
• burns
• adrenal insufficiency
• pulmonary embolism
• ruptured aortic aneurysm
• myocardial infarction
• hemorrhage
• cardiac tamponade
• drug withdrawal
• neuroleptic malignant syndrome
• systemic vasculitides
• exensive crush injury
• heatstroke
• dehydration
• systemic inflammatory response syndrome ( SIRS)

Management

• monitor:

• temperature
• blood pressure:

• mean arterial BP > 65
• target systolic BP 120-140 mm Hg

• heart rate
• respiratory rate
• pulse oximetry
• urine output
• mental status

• hydration with normal saline or lactated Ringer's
• central venous access

• keep central venous pressure > 8 mm Hg
• central venous oxygen saturation > 70%
• pulmonary artery catheterization not routinely indicated

• NPO ( nothing by mouth) until respiratory & mental status are stable
• oxygen to maintain SaO2 > 90%
• mechanical ventilation as indicated

• low tidal volume 6 mL/kg
• plateau pressures < 30 cm H2O

• removal of indwelling catheter (see catheter-related infection)
• prevention of septic shock (see septic & distributive shock)

• vasopressor as needed
• norepinephrine or dopamine if hypotension persists despite volume resuscitation
• target mean arterial pressure 60-65 mm Hg
• add dobutamine if low cardiac output despite hemoglobin and volume resuscitation

• antimicrobial therapy

• intravenous empiric antimicrobial therapy
• adjust antibiotics according to culture & sensitivities
• duration of therapy: 2 weeks (3-6 weeks for S. aureus)
• monotherapy with third generation cephalosporin or carbapenam for community-acquired septic shock
• coverage for MRSA & an anti- pseudomonas beta-lactam & & either a fluoroquinolone or an aminoglycoside for nosocomial infections, immunosuppression or recent antibiotic use
• addition of clindamycin to decrease toxin production for suspected toxic shock syndrome

• corticosteroid replacement

• if serum cortisol is < 9 ug/dL after 250 ug cosyntropin stimulaton test
• hydrocortisone 15-240 mg IV every 12 hours
• low dose corticosteroid (< 300 mg cortisol QD equivalent) for 5-11 days may improve outcomes [5]; of no benefit [6]; grade 2C recommendation [7]

• stress ulcer prophylaxis - ranitidine 50 mg IV every 8 hours
• DVT prophylaxis - TEDs/ SCD or subcutaneous heparin
• IV insulin to maintain plasma glucose 80-110 mg/dL [4]

• this is actually a questionable practice
• see glycemic control

• recombinant human activated protein C ( drotrecogin alfa) for severe sepsis & high risk of death if risk of bleeding is low [4,8]
• early broad-spectrum antibiotics & drotrecogin alfa independently associated with lower hospital mortality in ICU patients

More General Terms

• infection (infectious disease)
• bacteremia
• systemic inflammatory response syndrome (SIRS)

Additional Terms

• catheter-related infection
• distributive shock (multiple organ dysfunction syndrome)
• empiric antibiotic therapy
• mortality in emergency department sepsis (MEDS) score

References

1. nlmpubs.nlm.nih.gov/hstat/ahcpr/
2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 853-55
3. Clinical Practice Statement for Adult Sepsis, The Permanente Medical Group, Nov. 1999
4. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, American College of Physicians, Philadelphia 1998, 2006
5. Journal Watch 24(20):150, 2004 Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ. 2004 Aug 28;329(7464):480. Epub 2004 Aug 02. Review. <PubMed> PMID: [1] <Internet> [2]
6. Sprung CL et al, Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358:111 PMID: [3]
7. Dellinger RP et al, Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2008 Crit Care Med 2008, 36:296 PMID: [4]
8. Ferrer R et al. Effectiveness of treatments for severe sepsis: A prospective, multicenter, observational study. Am J Respir Crit Care Med 2009 Nov 1; 180:861. PMID: [5]
9. Walkey AJ et al. Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis. JAMA 2011 Nov 23/30; 306:2248 PMID: [6]
   - Goss CH and Carson SS Is severe sepsis associated with new-onset atrial fibrillation and stroke? JAMA 2011 Nov 23/30; 306:2264 PMID: [7]
10. Ovbiagele B et al. Level of systolic blood pressure within the normal range and risk of recurrent stroke. JAMA 2011 Nov 16; 306:2137 PMID: [8]
11. National Guideline Clearinghouse Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. ngc-guideline: [9]
    - Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Society of Critical Care Medicine ngc-guideline: [10]
    - Drotrecogin alfa (activated) for severe sepsis. (National Institute for Health and Clinical Excellence) ngc-guideline: [11]

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