Sepsis (main)

(Redirected from Septic shock)

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 BPM
  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

Adrenal crisis

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
    • Beta-2 agonism causes vasodilation, therefore needs to be used in conjunction with vasopressors

Steroids

  • Reasonable to initiate in septic shock in those without contraindications (ex. immunosuppression, wound healing issues, DKA, etc)
    • While stress dose steroids may shorten recovery time, they have NOT been consistently shown to decrease mortality
    • Consider dosing hydrocortisone 200 mg IV daily, separated into 2-4 times a day
    • Do not administer steroids for the treatment of sepsis in the absence of shock
  • Evidence
    • ADRENAL trial showed that stress dose steroids is associated with faster time to shock resolution and discharge from ICU[20]
    • 2024 Focused Update by the Society of Critical Care Medicine (same organization for Surviving Sepsis) suggests for stress steroids in septic shock, while recommending against high dose (>400mg qd) or short duration (<3 days) steroids[21]
    • Newer meta-analyses do not show an increased incidence of superinfections related to initiation of stress dose steroids[22]
  • Addition of fludrocortisone may not make a difference as hydrocortisone has both adrenocorticoid and mineralocorticoid effects
  • ACTH cosyntropin testing likely unreliable in critically ill patients
  • Steroids are associated with adverse effects such as hyperglycemia, hypernatremia, and neuromuscular weakness. Weight risks and benefits[23]

Esmolol

  • One open-label, single-center RCT showing ~40% reduction in mortality when esmolol paired with norepinephrine infusion, with goal HR 80 - 95 BPM[24]
  • 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, Mervyn 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. Venkatesh B, Finfer S, Cohen J, Rajbhandari D, Arabi Y, Bellomo R, Billot L, Correa M, Glass P, Harward M, Joyce C, Li Q, McArthur C, Perner A, Rhodes A, Thompson K, Webb S, Myburgh J; ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med. 2018 Mar 1;378(9):797-808. doi: 10.1056/NEJMoa1705835. Epub 2018 Jan 19. PMID: 29347874.
  21. Chaudhuri D, Nei AM, Rochwerg B, Balk RA, Asehnoune K, Cadena R, Carcillo JA, Correa R, Drover K, Esper AM, Gershengorn HB, Hammond NE, Jayaprakash N, Menon K, Nazer L, Pitre T, Qasim ZA, Russell JA, Santos AP, Sarwal A, Spencer-Segal J, Tilouche N, Annane D, Pastores SM. 2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia. Crit Care Med. 2024 May 1;52(5):e219-e233. doi: 10.1097/CCM.0000000000006172. Epub 2024 Jan 19. PMID: 38240492.
  22. Sligl WI, Milner DA Jr, Sundar S, Mphatswe W, Majumdar SR. Safety and efficacy of corticosteroids for the treatment of septic shock: A systematic review and meta-analysis. Clin Infect Dis. 2009 Jul 1;49(1):93-101. doi: 10.1086/599343. PMID: 19489712.
  23. Pitre T, Drover K, Chaudhuri D, Zeraaktkar D, Menon K, Gershengorn HB, Jayaprakash N, Spencer-Segal JL, Pastores SM, Nei AM, Annane D, Rochwerg B. Corticosteroids in Sepsis and Septic Shock: A Systematic Review, Pairwise, and Dose-Response Meta-Analysis. Crit Care Explor. 2024 Jan 19;6(1):e1000. doi: 10.1097/CCE.0000000000001000. PMID: 38250247; PMCID: PMC10798738.
  24. 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.