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Sepsis

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Sepsis

Initial Tests (lab, imaging)

Intermittent hemodialysis or continuous veno-venous hemofiltration for renal failure

Debride necrotic tissues: Drain or remove abscesses or other foci of infection.

Admission Criteria/Initial Stabilization

Aggressive fluid resuscitation with normal saline can result in nongap metabolic acidosis. Not likely with lactated Ringer solution.

NPO if intubation considered; otherwise, enteral feeds are preferred to preserve GI mucosal integrity (1)[C].

www.nlm.nih.gov/medlineplus/sepsis.html

Mortality is 10 " 50% overall. Poor prognostic factors include the inability to mount a fever (>40 °C), nonurinary source of infection, nosocomial infection, inappropriate antibiotic coverage, and certain comorbidities (AIDS, cancer, immunosuppression).

GI hemorrhage, DIC, hyperglycemia, de novo embolic foci of infection, ARDS, multiorgan failure, death

11 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 " 637.22 Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatric Critical Care Medicine. 2005;6(1):2 " 8.33 Raghunathan K, Shaw A, Nathanson B, et al. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis. Crit Care Med. 2014;42(7):1585 " 1591.44 De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779 " 789.55 Paul M, Lador A, Grozinsky-Glasberg S, et al. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev. 2014;(1):CD003344.66 Stockmann C, Spigarelli MG, Campbell SC, et al. Considerations in the pharmacologic treatment and prevention of neonatal sepsis. Paediatr Drugs. 2014;16(1):67 " 81.

  • Continuum from sepsis to multisystem organ failure (MSOF) is affected by age-specific physiologic variables in children.
  • SIRS in pediatric population requires that abnormality in temperature or WBC be present (2)[C].
  • Drug metabolism is reduced in children with severe sepsis. Monitor drug toxicity labs to prevent adverse effects.

Continuum from sepsis to multisystem organ failure (MSOF) is affected by age-specific physiologic variables in children.

SIRS in pediatric population requires that abnormality in temperature or WBC be present (2)[C].

Drug metabolism is reduced in children with severe sepsis. Monitor drug toxicity labs to prevent adverse effects.

Often more difficult to diagnose; change in mental status/behavior may be the only early manifestation.

EPIDEMIOLOGY

  • 3/1,000 population
  • Increasing incidence; 750,000 new cases annually in the United States
  • 2% of hospitalized patients

ETIOLOGY AND PATHOPHYSIOLOGY

  • Multifactorial: Widespread endothelial dysfunction, dysregulation of nitric oxide production, and activation of coagulation cascade leads to maldistribution of blood flow, tissue hypoperfusion, and resulting to organ dysfunction.
  • An imbalance between proinflammatory and anti-inflammatory mediators leads to systemic tissue damage and significant immunosuppression.
  • Causative organisms:Gram-positive bacteria (most common): Staphylococcus sp., Streptococcus sp., Enterococcus sp.Gram-negative: Escherichia coli, Klebsiella sp., Proteus sp., Pseudomonas sp. and anaerobic bacteriaFungi: Candida sp. (incidence increased 207% from 1976 to 2000)Causative organism not identified in 50 " “75% of cases
  • Common sites of infection: respiratory tract (most common), urinary tract, gastrointestinal tract, skin/soft tissue, CNS, bacteremia
  • Gram-positive bacteria (most common): Staphylococcus sp., Streptococcus sp., Enterococcus sp.
  • Gram-negative: Escherichia coli, Klebsiella sp., Proteus sp., Pseudomonas sp. and anaerobic bacteria
  • Fungi: Candida sp. (incidence increased 207% from 1976 to 2000)
  • Causative organism not identified in 50 " “75% of cases

RISK FACTORS

  • Extremes of age (very young or age >60 years)
  • Ethnicity: African American
  • Comorbidities: COPD, congestive heart failure (CHF), cancer, diabetes, and renal insufficiency/failure
  • Immunosuppression
  • Bacteremia
  • Community-acquired pneumonia
  • Complicated labor and delivery: premature labor and/or premature rupture of membranes, untreated maternal group B strep colonization
  • Nosocomial factors: surgical site infections, indwelling catheters

GENERAL PREVENTION

  • Vaccination: pneumococcal vaccine in children and also adults who are ≥65 years or with comorbidities placing them at high risk for disease. Haemophilus influenzae type B (infants, young children), influenza (H1N1 in pregnant women), meningococcal vaccine
  • Ž ³-Globulin for hypo- or agammaglobulinemia
  • Treat group B strep carriers during labor.
  • Regular hand washing, sterile technique for catheter placement, appropriate glove use
  • Antibiotic prophylaxis for recommended surgical procedures

COMMONLY ASSOCIATED CONDITIONS

  • Immunologic: neutropenia, HIV, hypo/agammaglobulinemia, complement deficiency, splenectomy, immunosuppressants (corticosteroids, chemotherapy, TNF-α antagonists)
  • Diabetes, alcoholism, malignancy, cirrhosis, burns, multiple trauma, IV drug abuse, malnutrition

DIAGNOSIS

HISTORY

  • Past medical, surgical, social, occupational, and travel history to identify risk factors and potential source
  • General symptomsFever, chills, rigors, myalgiasMental status changes: restlessness, agitation, confusion, delirium, lethargy, stupor, coma
  • Specific symptoms (relative to primary source)Respiratory: cough, sputum production, dyspnea, pleuritic chest painUrinary: dysuria, frequency, urgency, flank painIntra-abdominal: nausea, vomiting, diarrhea, constipation, abdominal painCNS: stiff neck, headache, photophobia, focal neurologic signs
  • Fever, chills, rigors, myalgias
  • Mental status changes: restlessness, agitation, confusion, delirium, lethargy, stupor, coma
  • Respiratory: cough, sputum production, dyspnea, pleuritic chest pain
  • Urinary: dysuria, frequency, urgency, flank pain
  • Intra-abdominal: nausea, vomiting, diarrhea, constipation, abdominal pain
  • CNS: stiff neck, headache, photophobia, focal neurologic signs

PHYSICAL EXAM

  • Assess vital signs: hyper/hypothermia, tachycardia, tachypnea, hypotension
  • Signs of poor perfusion: central venous hypoxia, delayed capillary refill, cyanosis, mottled skin
  • Signs of target organ involvement: jaundice, skin lesions (erythema, petechiae, embolic lesions, purpura)

DIFFERENTIAL DIAGNOSIS

  • Bacteremia without sepsis
  • Viral, rickettsial, spirochetal, and protozoal diseases
  • Collagen vascular diseases, vasculitides, pancreatitis, myocardial infarction, CHF, pulmonary embolism, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), thyrotoxicosis, adrenal insufficiency, poisoning, drug reaction

DIAGNOSTIC TESTS & INTERPRETATION

  • Two sets of blood cultures to document presence of bacteremia (not required for diagnosis; 50% of blood cultures are negative in severe sepsis/septic shock). Obtain cultures before antibiotic therapy. Do not delay the start of antibiotic therapy (1)[B].
  • Cultures/Gram stains from potential sites of infection (sputum, urine, pleural fluid, ascites, CSF, wound)
  • CBC with differential, CRP, coagulation profile, comprehensive metabolic profile, lactic acid level, arterial blood gas, urinalysis
  • Radiographic studies (plain films, ultrasound, CT, or MRI) to confirm source of infection
  • Aspiration, biopsy, and/or drainage of potentially infected body sites (pleural cavity, peritoneal cavity, biliary tree, CSF, abscess). Interventional radiology techniques to aid in specimen collection as needed
  • Echocardiogram if concern for endocarditis
  • Common findings: leukocytosis, bandemia (>10%), hyperglycemia, metabolic acidosis, mild hyperbiliru-binemia, hypoxemia, respiratory alkalosis, proteinuria
  • Less common findings (more severe disease): leukopenia, anemia, thrombocytopenia, coagulopathy, azotemia, hypoglycemia, acidosis

TREATMENT

GENERAL MEASURES

  • Assess oxygenation and supplement as needed. Intubate for respiratory failure.
  • Invasive monitoring for management of hemodynamic instability using goal-directed therapy.
  • Adequate volume resuscitation (30 mL/kg crystalloid for hypotension) within 3 hours of presentation and vasopressors for refractory hypotension (within 6 hours of presentation). Targets are:Central venous pressure (CVP) 8 to 12 mm Hg, MAP ≥65 mm Hg, urine output ≥0.5 mL/kg/hr (1)[A]Central/mixed venous O2 saturation ≥70%/65%If goals not met with fluid resuscitation and/or vasopressor, transfuse PRBCs to achieve hematocrit >30%; if still <70%, add dobutamine (1)[C].
  • Identify source of infection and remove septic foci:Early surgical consultation for acute abdomen, empyema, necrotizing fasciitisInterventional radiology consultation for guided drainage
  • Transfuse PRBCs, platelets, and/or fresh frozen plasma for coagulopathic complications or in association with planned procedures.Transfuse PRBC if Hgb <7.0 to target Hgb of 7.0 to 9.9 g/dL in absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1)[B]
  • Stress ulcer and DVT prophylaxis (1)[B]
  • Glucose control ( ≥180 mg/dL) (1)[A]
  • Central venous pressure (CVP) 8 to 12 mm Hg, MAP ≥65 mm Hg, urine output ≥0.5 mL/kg/hr (1)[A]
  • Central/mixed venous O2 saturation ≥70%/65%If goals not met with fluid resuscitation and/or vasopressor, transfuse PRBCs to achieve hematocrit >30%; if still <70%, add dobutamine (1)[C].
  • If goals not met with fluid resuscitation and/or vasopressor, transfuse PRBCs to achieve hematocrit >30%; if still <70%, add dobutamine (1)[C].
  • Early surgical consultation for acute abdomen, empyema, necrotizing fasciitis
  • Interventional radiology consultation for guided drainage
  • Transfuse PRBC if Hgb <7.0 to target Hgb of 7.0 to 9.9 g/dL in absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1)[B]

MEDICATION

  • Fluid managementInitial therapy: 30 mL/kg of crystalloids (1)[B]Consider adding albumin for patients requiring large volumes of crystalloid (1)[C],(3)[B].
  • VasopressorsNorepinephrine 0.01 to 3 Ž ¼g/kg/min (1,4)[B].Low-dose dopamine for renal protection is not recommended (1)[C].
  • Initiate broad-spectrum antibiotic within an hour of recognizing severe sepsis or septic shock (1,4)[A]:Adult (Pseudomonas not suspected): vancomycin (loading dose 25 mg/kg) + Gram-negative coverage (3rd-generation cephalosporin, Ž ²-lactam/ Ž ²-lactamase inhibitor, or carbapenem)Adult (Pseudomonas suspected): vancomycin + two agents aimed at resistant Gram-negative bacteria ceftazidime/cefepime/carbapenem/piperacillin " “tazobactam + either fluoroquinolone (ciprofloxacin) or aminoglycoside (gentamicin/amikacin) depending on local hospital sensitivitiesNonimmunocompromised child: 3rd-generation cephalosporinNeonate (<7 days old): ampicillin and gentamicin (5)[B]Consider narrowing antibiotic regimen at 48 to 72 hours based on culture results. Anticipate antibiotic course to last 7 to 10 days (1)[B].
  • Antifungals if fungal infection suspected: long-term antibiotic use, TPN, GI surgeryAdjuvant intravenous immunoglobulins (IVIGs) may reduce mortality in adults (6)[B].
  • Initial therapy: 30 mL/kg of crystalloids (1)[B]
  • Consider adding albumin for patients requiring large volumes of crystalloid (1)[C],(3)[B].
  • Norepinephrine 0.01 to 3 Ž ¼g/kg/min (1,4)[B].
  • Low-dose dopamine for renal protection is not recommended (1)[C].
  • Adult (Pseudomonas not suspected): vancomycin (loading dose 25 mg/kg) + Gram-negative coverage (3rd-generation cephalosporin, Ž ²-lactam/ Ž ²-lactamase inhibitor, or carbapenem)
  • Adult (Pseudomonas suspected): vancomycin + two agents aimed at resistant Gram-negative bacteria ceftazidime/cefepime/carbapenem/piperacillin " “tazobactam + either fluoroquinolone (ciprofloxacin) or aminoglycoside (gentamicin/amikacin) depending on local hospital sensitivities
  • Nonimmunocompromised child: 3rd-generation cephalosporin
  • Neonate (<7 days old): ampicillin and gentamicin (5)[B]
  • Consider narrowing antibiotic regimen at 48 to 72 hours based on culture results. Anticipate antibiotic course to last 7 to 10 days (1)[B].
  • Adjuvant intravenous immunoglobulins (IVIGs) may reduce mortality in adults (6)[B].
  • Possible interactionsAminoglycosides: increase in nephrotoxicity with enflurane, cisplatin, and possibly vancomycin; ototoxicity with loop diuretics; paralysis with neuromuscular-blocking agentsAdjust doses for renal and/or hepatic impairment.
  • The European Society of Intensive Care Medicine statement in critically ill patientsHydroxyethyl starches (HESs) with MW ≥200 kDA and/or degree of substitution >0.4 are not recommended in severe septic patients (1)[C].Hyperoncotic solutions should not be used in fluid resuscitation.

Possible interactions

  • Aminoglycosides: increase in nephrotoxicity with enflurane, cisplatin, and possibly vancomycin; ototoxicity with loop diuretics; paralysis with neuromuscular-blocking agents
  • Adjust doses for renal and/or hepatic impairment.

Aminoglycosides: increase in nephrotoxicity with enflurane, cisplatin, and possibly vancomycin; ototoxicity with loop diuretics; paralysis with neuromuscular-blocking agents

Adjust doses for renal and/or hepatic impairment.

The European Society of Intensive Care Medicine statement in critically ill patients

  • Hydroxyethyl starches (HESs) with MW ≥200 kDA and/or degree of substitution >0.4 are not recommended in severe septic patients (1)[C].
  • Hyperoncotic solutions should not be used in fluid resuscitation.

Hydroxyethyl starches (HESs) with MW ≥200 kDA and/or degree of substitution >0.4 are not recommended in severe septic patients (1)[C].

Hyperoncotic solutions should not be used in fluid resuscitation.

Ž ²-Lactam antibiotics, macrolides, and metronidazole generally are considered safe.

  • Vasopressors: epinephrine, vasopressin
  • Consider IV hydrocortisone 200 mg per day if the patient is poorly responsive to both IV fluid resuscitation and vasopressors (1)[C].
  • Inotropic therapy with dobutamine may benefit patients with myocardial dysfunction or ongoing hypoperfusion despite adequate intravascular volume and MAP (1)[C].

ADDITIONAL THERAPIES

SURGERY/OTHER PROCEDURES

INPATIENT CONSIDERATIONS

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • Place arterial line and central venous catheter in unstable patients
  • Chem " “7 and CBC daily; lactate, mixed venous oxygen saturation q2 " “4h in initial resuscitation period, and daily INR/PTT if DIC is a concern.
  • Follow antibiotic drug levels (vancomycin, gentamicin).
  • Foley catheter placement to monitor urine output

DIET

PATIENT EDUCATION

PROGNOSIS

COMPLICATIONS

REFERENCES

ADDITIONAL READING

  • Alejandria ‚ MM, Lansang ‚ MA, Dans ‚ LF, et al. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev. 2013;(9):CD001090.
  • Levy ‚ MM, Fink ‚ MP, Marshall ‚ JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250 " “1256.
  • Venkataraman ‚ R, Kellum ‚ JA. Sepsis: update in the management. Adv Chronic Kidney Dis. 2013;20(1):6 " “13.
  • Wiener ‚ RS, Wiener ‚ DC, Larson ‚ RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA. 2008;300(8):933 " “944.

CODES

ICD10

  • A41.9 Sepsis, unspecified organism
  • R65.10 SIRS of non-infectious origin w/o acute organ dysfunction
  • R65.20 Severe sepsis without septic shock
  • R65.21 Severe sepsis with septic shock
  • A41.59 Other Gram-negative sepsis
  • A41.51 Sepsis due to Escherichia coli [E. coli]
  • A41.52 Sepsis due to Pseudomonas
  • A41.2 Sepsis due to unspecified staphylococcus
  • A41.81 Sepsis due to Enterococcus
  • R65.11 SIRS of non-infectious origin w acute organ dysfunction

ICD9

  • 995.91 Sepsis
  • 995.90 Systemic inflammatory response syndrome, unspecified
  • 038.9 Unspecified septicemia
  • 785.52 Septic shock
  • 995.92 Severe sepsis
  • 038.10 Staphylococcal septicemia, unspecified
  • 038.42 Septicemia due to escherichia coli [E. coli]
  • 038.0 Streptococcal septicemia
  • 038.49 Other septicemia due to gram-negative organisms
  • 038.2 Pneumococcal septicemia [Streptococcus pneumoniae septicemia]
  • 038.43 Septicemia due to pseudomonas

SNOMED

  • 91302008 Sepsis (disorder)
  • 238149007 systemic inflammatory response syndrome (disorder)
  • 10001005 Bacterial septicemia (disorder)
  • 76571007 Septic shock (disorder)
  • 447894003 Sepsis due to Staphylococcus (disorder)
  • 310669007 Septicemia due to enterococcus (disorder)
  • 448418006 Sepsis due to Streptococcus (disorder)

CLINICAL PEARLS

  • Treat sepsis aggressively with fluid support (with hemodynamic monitoring and pressor support if necessary) early use of broad-spectrum antimicrobial therapy and removal/drainage of foci of infection.
  • Despite aggressive treatment, overall mortality is high (10 " “50%) in patients with severe sepsis/septic shock.