Sepsis (Main)

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Background

  • Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection[1]
  • The infection is most commonly by bacteria, but can also be by fungi, viruses, or parasites[2]
  • Risk of death from sepsis being as high as 30%, severe sepsis as high as 50%, and septic shock as high as 80% [3]
  • The most common primary sources of infection resulting in sepsis are the lungs, the abdomen, and the urinary tract[4]
  • Sepsis carries a 40% in hospital mortality[1]
  • Positive cultures are not obligatory in the diagnosis of sepsis
  • Pneumonia, abdominal abscess and pyelonephritis are common primary causes of sepsis

Definition Changes

In 2016 new definitions were adopted for the evaluation and diagnosis of Sepsis, Severe Sepsis and Septic shock[5]

Old definition New 2016 definition
Sepsis 2 SIRS + suspected infection Life threatening organ dysfunction caused by dysregulated host response to infection. Suspected/documented infection + 2 on the qSOFA:
  • Hypotension with SBP <100 or
  • altered mental status or
  • Tachypnea (RR >/=22) OR
  • Increase in SOFA score by 2 points
Severe sepsis *Sepsis +
  • SBP< 90 or
  • MAP <65 lactate >2 or
  • INR >1.5 or
  • Bili>2 or
  • Urine output <0.5ml/kg/h
  • Creatinine>2.2 or
  • Platelets <100 or
  • SpO@<90%
No longer a category
Septic shock Sepsis + hypotension after adequate fluid resuscitation Sepsis + vasopressors needed to maintain MAP>65 + lactate >2

qSOFA Score

Quick Sequential (Sepsis Related) Organ Failure Assessment Score

  • Respiratory rate of 22/min or greater (+1 Point)
  • Altered mentation (+1 Point)
  • Systolic blood pressure of 100 mm Hg or less (+1 Point)

SOFA Score

  • The SOFA is generally used in the ICU and can stratify the mortality of patients based on the initial score and subsequent changes in score

MEDS score

  • The Mortality in Emergency Department Sepsis (MEDS) prediction rule is a proposed method to risk stratify ED patients with sepsis

NEWS 2 Score

  • National Early Warning Score (NEWS) 2 determines degree of critically ill patient, in non-pregnant patients ≥16 years old[6]
  • Used by the UK NHS to identify acutely ill patients, including those with sepsis
  • Not reliable in spinal cord injury patients due to disturbance of autonomic responses
  • Combination of:
    • Respiratory rate
    • Presence of hypercapnic respiratory failure
    • Presence of supplemental O2
    • Temperature
    • SBP
    • Pulse rate
    • Consciouness
  • See below for MDCalc link

Systemic Inflammatory Response Syndrome (SIRS) Criteria

  • Still acceptable to use in ED depending on local protocol
  • Misses up to 1/8 very septic ICU patients[7]


  • ≥2 of 4 criteria must be present:
  1. Temperature >38°C (100.4F) or <36°C (96.9F)
  2. HR >90 BMP
  3. RR >20 breaths/minute or PaCO2 <32 mmHg
  4. WBC count >12,000/mm3, <4,000/mm3, or >10% bands/immature forms

Clinical Features

Sepsis

Life-threatening organ dysfunction caused by a dysregulated host response to infection. This only needs to include one of the following:[8]

Septic shock

Patients with sepsis and any of the following:[1]

  1. Vasopressor requirement to maintain a mean arterial pressure > 65 mm Hg
  2. Serum lactate level greater than 2 mmol/L (>18mg/dL) in the absence of hypovolemia.

Differential Diagnosis

Shock

Evaluation

Work-Up

Time Specific Management

Time of presentation is defined as the time of triage in the emergency department

3 hour goals[9]

  • Measure lactate level
  • Obtain blood cultures prior to administration of antibiotics
  • Administer broad spectrum antibiotics
  • Administer 30ml/kg crystalloid for hypotension or lactate ≥4mmol/L

6 hour goals[9]

  • Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) ≥65mmHg
  • If persistent hypotension after initial fluid administration (MAP < 65 mm Hg) or if initial lactate was ≥4 mmol/L, reassess volume status and tissue perfusion:
    • Option 1: Focused Exam
      • Vital signs
      • Cardiopulmonary Exam
      • Capillary Refill
      • Peripheral Pulse
      • Skin Exam
    • Option 2: Two of the following
      • Measure CVP (IVC ultrasound) with following goals:
        • >8 cmH2O, not intubated
        • >12 cmH2O, intubated
      • Measure ScvO
      • Bedside cardiovascular ultrasound
      • Dynamic assessment of fluid responsiveness with passive leg raise or fluid challenge

A central line and measurement of ScvO2 is not required and does not impact mortality[10][11][12]

Circulation Managment

IVF

  • Guidelines recommend initial 30 cc/kg bolus (generally 2L in average adult)
  • Reassess patient's volume status after initial bolus. Auscultate for pulmonary edema. Evaluate peripheral circulation. Consider IVC ultrasound
  • Septic patients can be euvolemic but remain hypotensive due to vasodilation. Consider early vasopressors.
  • Increasing evidence that excessive fluid resuscitation can be harmful.
    • Positive fluid balance on day 3 of hospital admission independently associated with increasing mortality [13]
    • Protocolized fluid administration (e.g. traditional Early Goal Directed Therapy) has no mortality benefit over usual care. [14] [15]
    • High volume (5+ L) resuscitation associated with increased mortality. [16]
  • Consider assessing diastolic dysfunction via echo in CHF patients in whom IVC ultrasound is not reliable


Pressors

  • Indicated if MAP<60 despite adequate IVF or if IVF are contraindicated
  • Best if given when the vascular space is filled; ok if it is not

Options:

  • Norepinephrine (5-20mcg/min) - 1st line[17]
  • Epinephrine (1-20 mcg/min) - 2nd line
  • Vasopressin (0.03 units/minute fixed dose) can be added to norepinephrine (NE)
    • as a 2nd line agent may reduce arrhythmia's compared to other pressors with catecholamine properties[18]
  • Dopamine should be used hesitantly and only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia)
    • Do not use Low-dose dopamine for renal protection
    • Dopamine may have increased mortality rates compared to other vasopressors, especially in the pediatric septic patient[19]
  • Phenylephrine should not be used for treating septic shock except if:
    • Norepinephrine is associated with serious arrhythmias
    • Cardiac output is known to be high and blood pressure persistently low
    • As salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target
  • Milrinone
  • Methylene blue consideration for septic shock refractory to catecholaminergic pressors

Inotropes

  • Dobutamine (2-20mcg/kg/min) may be added if:
    • Myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output
    • Ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP

Steroids

  • Controversial and only shown to relieve shock faster in those who have resolution of shock but may increase the risk of infection
    • Consider hydrocortisone 50-100mg in ED (200-300mg QD in 2-4x/d dosing) if pressor/fluid resistant (SBP < 90 persistently)
  • ACTH cosyntropin testing likely unreliable in critically ill patients
  • Do not administer steroids for the treatment of sepsis in the absence of shock

Esmolol

  • One single-center RCT showing ~40% reduction in mortality when esmolol paired with norepinephrine infusion, with goal HR 80 - 95 BPM[20]
  • All patients were fluid resuscitated, intubated, given hydrocortisone 300 mg/day
  • Will require further multi-center RCTs to confirm findings

Infection Control

Source control

Antibiotics

Blood Products

RBCs

Only transfuse RBCs when hemoglobin decreases to <7.0 g/dL (goal is 7.0 –9.0 g/dL in adults)

Erythropoietin

Do not use erythropoietin as a specific treatment of anemia associated with severe sepsis

Platelets

  • In severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 x 109/L) in the absence of apparent bleeding
  • If < 20,000/mm3 (20 x 109/L) and significant risk of bleeding then administer platelets.
  • <50,000/mm3 (50 x 109/L) if there is active bleeding, planned surgery or other procedures.

Disposition

  • Admit, possibly to step-down or ICU

External Links

See Also

References

  1. 1.0 1.1 1.2 Singer, Melvyn et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287
  2. Jui, Jonathan (2011). "Ch. 146: Septic Shock". In Tintinalli, Judith E.; Stapczynski, J. Stephan; Ma, O. John; Cline, David M. et al. Tintinalli's Emergency Medicine: A Comprehensive Study Guide (7th ed.). New York: McGraw-Hill. pp. 1003–14.
  3. Jawad, I; Lukšić, I; Rafnsson, SB (June 2012). "Assessing available information on the burden of sepsis: Global estimates of incidence, prevalence and mortality". Journal of Global Health 2 (1): 010404. doi:10.7189/jogh.02.010404 (inactive 2015-02-02). PMC 3484761. PMID 23198133 full text
  4. Munford, Robert S.; Suffredini, Anthony F. (2014). "Ch. 75: Sepsis, Severe Sepsis and Septic Shock". In Bennett, John E.; Dolin, Raphael; Blaser, Martin J.. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (8th ed.). Philadelphia: Elsevier Health Sciences. pp. 914–34.
  5. Seymour, C. Assessment of Clinical Criteria for Sepsis For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):762-774. doi:10.1001/jama.2016.0288.
  6. Royal College of Physicians. National Early Warning Score (NEWS) 2: Standardising the assessment of acute-illness severity in the NHS. Updated report of a working party. London: RCP, 2017.
  7. Kaukonen KM, Bailey M, Bellomo R. Systemic Inflammatory Response Syndrome Criteria for Severe Sepsis. The New England journal of medicine. 373(9):881. 2015.
  8. Seymour, C. Assessment of Clinical Criteria for Sepsis For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):762-774. doi:10.1001/jama.2016.0288.
  9. 9.0 9.1 Surviving Sepsis Updated Bundles in Response to New Evidence full text
  10. ProCESS Investigators,Yealy DM, Kellum JA, Juang DT, et al.A randomized trial of protocol-based care for earlyseptic shock. N Engl J Med 2014;370(18):1683-1693 Full Text
  11. The ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med2014; 371:1496-1506
  12. Mouncey PR, Osborn TM, Power GS, et al for the ProMISe trial investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015:DOI: 10.1056/NEJMoa1500896
  13. Sakr Y et al. Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit. Critical care medicine. 45(3):386-394, Mar 2017.
  14. Yealy DM, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370:1683-93. DOI: 10.1056/NEJMoa1401602
  15. Mouncey PR, et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med 2015;372:1301-11. DOI: 10.1056/NEJMoa1500896
  16. Marik PE, et al. Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med (2017) 43:625–632 DOI 10.1007/s00134-016-4675-y
  17. EBQ:SOAP II Trial
  18. McIntyre, W. F., Um, K. J., Alhazzani, W., Lengyel, A. P., Hajjar, L., Gordon, A. C., … Belley-Côté, E. P. (2018). Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock. JAMA: The Journal of the American Medical Association, 319(18), 1889.
  19. Ventura AM, Shieh HH, Bousso A, Goes PF, Fernandes IC, de Souza DC, et al. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrineas First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med 2015;43:2292-302.
  20. Andrea Morelli et al. Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock: A Randomized Clinical Trial. JAMA. 2013;310(16):1683-1691.

Authors:

Ross Donaldson