Sepsis resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]

Definition

• Sepsis = Infection + SIRS

• The presence of systemic inflammatory syndrome (SIRS) is due to many factors. The presence of infection increases the chances of sepsis and increase the SIRS criteria .

• The endothelial dysfunction is the main trigger transforming the localized infection into systemic organ dysfunction

• There is no definitive biomarkers have been associated with the endothelial dysfunction of sepsis.

SIRS is diagnosed by 2 or more of the following:

• Tachycardia > 90 bpm
• Tachypnea > 20 breaths per minute or on blood gas, a P_aCO₂ < 32 mm Hg
• Temperature < 36 (96.8 °F) or > 38 °C (100.4 °F)
• White blood cell count < 4000 cells/mm³ ( < 4 x 10⁹cells/L ) or > 12000 cells/mm³ ( > 12 x 10⁹ cells/L) or > 10% bandemia ( immature WBCs ).

Sepsis is diagnosed by at least 1 of the following signs of organ failure: [HOME]

• Hypoxemia (arterial oxygen tension [PaO2] < 72 mm Hg at fraction of inspired oxygen [FiO2] 0.21; overt pulmonary disease not the direct cause of hypoxemia)
• Oiguria (urine output < 30 mL or 0.5 mL/kg for at least 1 h)
• Mental status alteration
• Elevated plasma lactate level > 4 mmol/L

Severe sepsis

• Sepsis + organ dysfunction
• Organ damage can present as decreased urine output, acute kidney injury, and elevated liver function tests.

Septic shock

• Severe sepsis + persistent hypotension after adequate fluid challenge.

Multiple organ dysfunction syndrome (MODS) is the presence of altered organ function in a acutely ill patient whom homeostasis cannot be maintained without intervention.

Diagnostic Criteria For Sepsis (Documented/Suspected Infection Plus Inflammatory variablesPlus One of The Organ Dysfunction)

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General variables

• Fever > 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
• Edema
• Positive fluid balance ( > 20 mL/kg over 24 hr)
• Hyperglycemia ( plasma glucose > 140 mg/dL or 7.7 mmol/L ) in the absence of diabetes

Inflammatory variables

• Leukocytosis ( WBC count > 12,000 µL–1 )
• Leukopenia ( WBC count < 4000 µL–1 )
• Immature WBCs forms are > 10% with normal count
• Plasma C-reactive protein > 2 SD above the normal value
• Plasma procalcitonin > 2 SD above the normal value
• Hemodynamic variables
• Arterial hypotension after 30 ml/kg fluid bolus ( SBP < 90 mm Hg, MAP < 70 mm Hg, or an SBP decrease > 40 mm Hg in adults or < 2 SD below normal for age )

Organ dysfunction variables

• Arterial hypoxemia ( Pao2/Fio2 < 300 )
• Acute oliguria ( urine output < 0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation )
• Creatinine increase > 0.5 mg/dL or 44.2 µmol/L
• Coagulation abnormalities ( INR > 1.5 or aPTT > 60 Sec )
• Ileus ( absent bowel sounds )
• Thrombocytopenia ( platelet count < 100,000 µL–1 )
• Hyperbilirubinemia ( plasma total bilirubin > 4 mg/dL or 70 µmol/L )
• Tissue perfusion variables
• Hyperlactatemia > 1 mmol/L
• Decreased capillary refill or mottling
• Evidence of acute lung injury (ALI):

1. Oxygenation abnormality with a PaO2/FiO2 ratio < 300
2. Chest Xray with bilateral opacities compatible with pulmonary edema
3. PA < 18 mm Hg or no clinical evidence of left atrial hypertension if PaO2 is not available

• Acute respiratory distress syndrome (ARDS) is a more severe form of ALI and is defined similarly but a characteristic PaO2/FiO2 ratio is < 200

Causes

Life Threatening Causes

• Bacteremia: 95% of positive blood cultures were associated with sepsis, severe sepsis, or septic shock.. However septic shock can occur without bacteremia "viable bacteria in the blood". In fact, septic shock is associated with culture-positive bacteremia in only 30-50% of cases.

Common Causes

• Community acquired pneumonia: 48% develop severe sepsis.
• Diabetes and renal disease may explain the higher rates of infection related septic shock.
• Immunosuppression

Prognosis

• Advanced age > 65 year old: a strong correlation exists between the incidence of septic shock in patients older than 50 years.
• Organ dysfunction is more related to bad prognosis than meeting SIRS criteria. A study found that just meeting SIRS criteria without evidence of organ dysfunction did not predict increased mortality. This concludes the importance of identification of organs dysfunction over the presence of SIRS criteria.

Management

Goals during the first six hours of fluid resuscitation, as suggested by the Surviving Sepsis Campaign guidelines, include the following:

• CVP 8-12 mmHg
• SCVo2 (superior vena cava) 70% or SVo2 65%
• MAP ≥ 65 mmHg
• Urine output ≥ 0.5 mL/kg/hour

Sepsis screening Patient identification

History of infection

Yes, history of infection

No History

Yes,Clinical symptoms

No clinical symptoms

Activate Sepsis Protocol Blood culture 2X, then early antibiotics within 1 hr Check lactate elevation, evidence of organ dysfunction

No lactate No evidence of organ dysfunction Normal tissue perfusion

Tissue hypoperfusion

Yes, Tissue hypoperfusion

No tissue hypoperfusion

SBO ≤ 90mm Hg MAP ≤ 65 mm Hg Lactate ≥ 4mmol/L

Protocol A and B

Protocol B

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PROTOCOL A Sepsis-induced Hypoperfusion Clinical picture plus < 65mm Hg Lactate > 4mmol/L

Supplemental O2 (Targeted by O2) Fluid resuscitation at least crystalloid bolus or colloid equivalent 20ml/kg

CVP measurement

CVP < 8mm Hg

Crystalloid bolus or colloid equivalent till CVP > 8 mm Hg

CVP > 8mm Hg

MAP

MAP < 65 mmHg

Vasopressors ( 1st line Norepinephrine 0.05 mcg/kg/min ) ( 2nd line Dopamine / Vasopressin ) (3rd-4th line Phenylephrine ) till MAP > 65 mmHg

MAP > 65 mmHg

SeVO2

SeVO2 < 70%

SeVO2 > 70%

Transfuse PRBCs, if HCT ≤ 30 Dobutamine if HCT > 30

Goals achieved

Goals achieved

Resuscitation completed Reevaluate

Vasopressors still required Stress Dose Steroids

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PROTOCOL B Sepsis shock with NO tissue hypoperfusion Normal Perfusion

Assess requirement for Mechanical ventilation (Targeted by O2)

Infection source identification Empirical antibiotics after 2 blood cultures

Plasma glucose level

Mechanical ventilation required

No mechanical ventilation required

< 180 mg/dl maintain < 150 mg/dl

> 180 mg/dl

Semi Recumbent position Lung-protective ventilation for ALI/ARDS Maintain intermittent positive pressure (IPPP) < 30 cm H2o

Start insulin to keep glucose < 150

Do's

Do within 3 Hours

1. Measure lactate level.
2. Obtain at least 2 sets of blood cultures and cultures of other relevant sites, provided it does not cause a delay exceeding 45 minutes in starting antimicrobial therapy.
3. Administer broad spectrum antibiotics at least 1 drug with activity against all likely pathogens ( bacterial, fungal, or viral )
4. Administer adequate fluid challenge (40-60 mL/kg) crystalloid for hypotension or lactate 4 mmol/L.
5. Maintian CVP 8-12 cm H2o in non-intubated patients, and CVP 12-15 cm H2o for intubated patients.

Do within 6 Hours

1. Apply vasopressors in hypotension refractory to initial fluid resuscitation.
2. Maintain a mean arterial pressure (MAP) ≥ 65 mm Hg.
3. In persistent arterial hypotension despite volume resuscitation or initial lactate 4 mmol/L ( 36 mg/dL ): check CVPand ScvO2.
4. Re-measure lactate if initial lactate was elevated.
5. Initiating broad-spectrum coverage until the specific organism is cultured and antibiotic sensitivities are determined is important.

Don'ts

• Routine use of hemodynamic drugs to raise cardiac output to supranormal levels is not recommended.
• Increasing the cardiac index in order to enhance the oxygen delivery has no improvement on outcome but it has worsened morbidity and mortality.
• Administration of bicarbonate in order to correct the acidosis may worsen the intracellular acidosis. Correction of acidemia with sodium bicarbonate has not been proved to improve hemodynamics in a critically ill patient with increased blood lactate levels.
• Immunosuppressive agents that could suppress the overwhelming inflammatory mediators responsible for MODs, as high-dose corticosteroids, have not shown any benefit in humans. However the encouraging data from animal studies.
• Unfractionated heparin in patients with sepsis did not have any beneficial effect on length of hospital stay, MODs, and mortality compared to placebo.