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==Background==
==Background==
*Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection<ref name="sepsis definition">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</ref>
*Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection<ref name="sepsis definition">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</ref>
*The infection is most commonly by bacteria, but can also be by fungi, viruses, or parasites<ref>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. </ref>  
*The infection is most commonly by [[bacteria]], but can also be by [[fungi]], [[viruses]], or [[parasites]]<ref>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. </ref>  
*Risk of death from sepsis being as high as 30%, severe sepsis as high as 50%, and septic shock as high as 80% <ref>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 [http://www.jogh.org/documents/issue201201/12-Article%20Jawad.pdf full text]</ref>  
*Risk of death from sepsis being as high as 30%, severe sepsis as high as 50%, and septic shock as high as 80% <ref>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 [http://www.jogh.org/documents/issue201201/12-Article%20Jawad.pdf full text]</ref>  
*The most common primary sources of infection resulting in sepsis are the lungs, the abdomen, and the urinary tract<ref>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.</ref>
*The most common primary sources of infection resulting in sepsis are the [[pneumonia|lungs]], the abdomen, and the [[UTI|urinary tract]]<ref>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.</ref>
*Sepsis caries a 40% in hospital mortality<ref name="sepsis definition"></ref>
*Sepsis carries a 40% in hospital mortality<ref name="sepsis definition"></ref>
*Positive cultures are not obligatory in the diagnosis of sepsis
*[[Pneumonia]], abdominal abscess and [[pyelonephritis]] are common primary causes of sepsis
===Definition Changes===
===Definition Changes===
''In 2016 new definitions were adopted for the evaluation and diagnosis of Sepsis, Sever Sepsis and Septic shock''
''In 2016 new definitions were adopted for the evaluation and diagnosis of Sepsis, Severe Sepsis and Septic shock<ref> 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.</ref>''
{| {{table}}
{| {{table}}
| align="center" style="background:#f0f0f0;"|
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|-
|-
| '''Sepsis'''||2 [[SIRS]] + suspected infection||Life threatening organ dysfunction caused by dysregulated host response to infection. Suspected/documented infection + 2 on the [[qSOFA]]:
| '''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
*[[Hypotension]] with SBP <100 or
*AMS or
*altered mental status or
*Tachypnea (RR >/=22) OR
*Tachypnea (RR >/=22) '''OR'''
*Increase in [[SOFA]] score by 2 points
*Increase in [[SOFA]] score by 2 points
|-
|-
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*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
*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


==Clinical Presentation==
===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<ref>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.</ref>
*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
 
{{SIRS Score}}
 
==Clinical Features==
===Sepsis===
===Sepsis===
''Life-threatening organ dysfunction caused by a dysregulated host response to infection. This only needs to include one of the following:<ref> 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.</ref>''
''Life-threatening organ dysfunction caused by a dysregulated host response to infection. This only needs to include one of the following:<ref> 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.</ref>''
*Hypotension with SBP <100 or
*[[Hypotension]]with SBP <100 or
*AMS or
*[[Altered mental status]] or
*Tachypnea (RR >/=22) OR
*[[Tachypnea]] (RR >/=22) '''OR'''
*Increase in SOFA score by 2 points
*Increase in SOFA score by 2 points


===Septic shock===
===[[Septic shock]]===
Patients with sepsis and any of the following:<ref name="sepsis definition"></ref>
Patients with sepsis and any of the following:<ref name="sepsis definition"></ref>
#Vasopressor requirement to maintain a mean arterial pressure > 65 mm Hg  
#[[Vasopressors|Vasopressor]] requirement to maintain a mean arterial pressure > 65 mm Hg  
#Serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia.
#Serum [[lactate]] level greater than 2 mmol/L (>18mg/dL) in the absence of [[hypovolemia]].


==Differential Diagnosis==
==Differential Diagnosis==
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{{Shock DDX}}
{{Shock DDX}}


{{AMS and fever DDX}}
==Evaluation==
 
==Diagnosis==
===Work-Up===
===Work-Up===
*CBC
*CBC
*UA/Urine culture
*[[Urinalysis]]/Urine culture
*[[Blood culture]]
*[[Blood culture]]
*[[CXR]]
*[[CXR]]
*Chem
*Chem
*LFT
*[[LFTs]]
*Lipase
*Lipase
*VBG
*[[VBG]]
*Lactate
*[[Lactate]]
*Procalcitonin
*Coags
*Coags
*DIC panel (fibrinogen, D-dimer, FDP)
*Consider:
*T&S
**[[Procalcitonin]]
*?CT head/LP
**[[DIC]] panel (fibrinogen, [[D-dimer]], FDP)
*?TSH (thyroid storm)
**T&S
*?Cosyntropin stim vs. random cortisol (adrenal insufficiency)
**[[CT head]] and/or [[LP]
**TSH ([[thyroid storm]])
**Cosyntropin stim vs. random cortisol (adrenal insufficiency)
**Pelvic exam ([[toxic shock syndrome]], tampon)
**[[Influenza]] rapid testing
**CT Abd/Pelvis (abscess, other)
**spine imaging ([[epidural abscess]], other)


==Time Specific Management==
==Time Specific Management==
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*Apply [[vasopressors]] (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) ≥65mmHg
*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:
*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:
**Repeat focused exam OR any two of the following:
**Option 1: Focused Exam
***Measure CVP  
***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
***Measure ScvO
***Bedside [[Ultrasound: In Shock and Hypotension|cardiovascular ultrasound]]
***Bedside [[Ultrasound: In Shock and Hypotension|cardiovascular ultrasound]]
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==Circulation Managment==
==Circulation Managment==
===[[IVF]]===
===[[IVF]]===
*Reassess after each bolus
*Guidelines recommend initial 30 cc/kg bolus (generally 2L in average adult)
*Average is 5-6L w/in first 6hr
*Reassess patient's volume status after initial bolus. Auscultate for pulmonary edema.  Evaluate peripheral circulation.  Consider IVC ultrasound
*Careful reassessment of volume status is required in in patients with significantly depressed ejection fraction.
*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  <ref>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.</ref>
**Protocolized fluid administration (e.g. traditional Early Goal Directed Therapy) has no mortality benefit over usual care. <ref> 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 </ref> <ref> 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 </ref>
**High volume (5+ L) resuscitation associated with increased mortality. <ref>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 </ref>
*Consider assessing [[diastolic dysfunction]] via echo in [[CHF]] patients in whom IVC [[ultrasound]] is not reliable
 
 
===[[Pressors]]===
===[[Pressors]]===
*Indicated if MAP<60 despite adequate IVF or if IVF are contraindicated
*Indicated if MAP<60 despite adequate IVF or if IVF are contraindicated
*Best if given when the vascular space is filled; ok if it's not
*Best if given when the vascular space is filled; ok if it is not
'''Options:'''
'''Options:'''
*[[Norepinephrine]] (5-20mcg/min) - 1st line
*[[Norepinephrine]] (5-20mcg/min) - 1st line<ref>[[EBQ:SOAP II Trial]]</ref>
*[[Epinephrine]] (1-20 mcg/min) - 2nd line
*[[Epinephrine]] (1-20 mcg/min) - 2nd line
*[[Vasopressin]] (0.03 units/minute fixed dose) can be added to norepinephrine (NE)
*[[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<ref>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.</ref>
*''[[Dopamine]] should be used hesitantly and only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia)
*''[[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
**Do not use Low-dose [[dopamine]] for renal protection
**Dopamine may have increased mortality rates compared to other vasopressors<ref>Ventura AM, Shieh HH, Bousso A, Goes PF, Fernandes IC, de Souza DC, et al. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med 2015;43:2292-302. </ref>  
**Dopamine may have increased mortality rates compared to other vasopressors, especially in the pediatric septic patient<ref>Ventura AM, Shieh HH, Bousso A, Goes PF, Fernandes IC, de Souza DC, et al. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus [[Epinephrine]]as First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med 2015;43:2292-302. </ref>  
*''[[Phenylephrine]] should not be used for treating septic shock except if:
*''[[Phenylephrine]] should not be used for treating septic shock except if:
**Norepinephrine is associated with serious arrhythmias
**Norepinephrine is associated with serious arrhythmias
**Cardiac output is known to be high and blood pressure persistently low
**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
**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


===[[Vasopressors|Inotropes]]===
===[[Vasopressors|Inotropes]]===
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===[[Steroids]]===
===[[Steroids]]===
*[[EBQ:CORTICUS_Trial|Controversial and only shown to relieve shock faster]] in those who have resolution of shock but may increase the risk of infection
*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 (200-300 mg qd in 2-4x/d dosing) if pressor/fluid resistant (SBP < 90 persistently)
**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
*ACTH cosyntropin testing likely unreliable in critically ill patients
*Do not administer steroids for the treatment of sepsis in the absence of shock
*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<ref>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.</ref>
*All patients were fluid resuscitated, intubated, given hydrocortisone 300 mg/day
*Will require further multi-center RCTs to confirm findings


==Infection Control==
==Infection Control==
*Source Control
===Source control===
*Remove infected lines, surgery if indicated
*Remove any infected lines
*Drain [[abscesses]]
*Consult surgery or other specialists if indicated (e.g. for [[appendicitis]], [[cholangitis]], etc.)


===Antibiotics===
===Antibiotics===
*Administer within 3 hours
*Administer within 3 hours
*Initial choice dependant on suspected source, local antibiogram, and severity of illness
*See [[Initial Antibiotics in Sepsis (Main)]]
*See [[Initial Antibiotics in Sepsis (Main)]]


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*If < 20,000/mm3 (20 x 10<sup>9</sup>/L) and significant risk of bleeding then administer platelets.
*If < 20,000/mm3 (20 x 10<sup>9</sup>/L) and significant risk of bleeding then administer platelets.
*<50,000/mm3 (50 x 10<sup>9</sup>/L) if there is active bleeding, planned surgery or other procedures.
*<50,000/mm3 (50 x 10<sup>9</sup>/L) if there is active bleeding, planned surgery or other procedures.
==Disposition==
*Admit, possibly to step-down or ICU


==External Links==
==External Links==
*[http://www.mdcalc.com/sirs-sepsis-and-septic-shock-criteria/ MDCalc - SIRS, Sepsis, and Septic Shock Criteria]
*[http://www.mdcalc.com/sirs-sepsis-and-septic-shock-criteria/ MDCalc - SIRS, Sepsis, and Septic Shock Criteria]
*[http://www.mdcalc.com/qsofa-quick-sofa-score-for-sepsis-identification/ MDCalc - qSOFA Score]
*[http://www.mdcalc.com/qsofa-quick-sofa-score-for-sepsis-identification/ MDCalc - qSOFA Score]
*[https://www.mdcalc.com/national-early-warning-score-news-2#evidence MDCalc - NEWS 2]
*[http://emcrit.org/podcasts/sepsis-3/ EMCrit Sepsis 3.0]
*[http://emcrit.org/podcasts/sepsis-3/ EMCrit Sepsis 3.0]


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*[[Sepsis (Peds)]]
*[[Sepsis (Peds)]]
*[[EBQ:ProCESS Trial]]
*[[EBQ:ProCESS Trial]]
*[[Quick Sequential (Sepsis Related) Organ Failure Assessment Score (qSOFA)]]


==References==
==References==

Revision as of 20:15, 27 November 2019

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

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.
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