Sepsis (main): Difference between revisions

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{{AdultPage|Sepsis (peds)}}
{{AdultPage|Sepsis (peds)}}
==Background==
==Background==
*Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection<ref name="sepsis definition">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</ref>
*Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection<ref name="sepsis3">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</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>
*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>
*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 carries a 40% in hospital mortality<ref name="sepsis definition"></ref>
*Sepsis and septic shock are major healthcare problems, killing between one in three and one in six of those affected<ref name="SSC2021">Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021;49(11):e1063-e1143.</ref>
*In-hospital mortality for septic shock is approximately 30-40%<ref name="SSC2021"/>
*Positive cultures are not obligatory in the diagnosis of sepsis
*Positive cultures are not obligatory in the diagnosis of sepsis
*[[Pneumonia]], abdominal abscess and [[pyelonephritis]] are common primary causes of sepsis
*[[Pneumonia]], intra-abdominal infections, and [[pyelonephritis]] are the most common primary causes
===Definition Changes===
 
''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>''
===Sepsis-3 Definitions (2016)===
''In 2016 new definitions were adopted for the evaluation and diagnosis of Sepsis and Septic Shock<ref name="seymour">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;"|
| align="center" style="background:#f0f0f0;"|
| align="center" style="background:#f0f0f0;"|'''Old definition'''
| align="center" style="background:#f0f0f0;"|'''Old Definition'''
| align="center" style="background:#f0f0f0;"|'''New 2016 definition'''
| align="center" style="background:#f0f0f0;"|'''Sepsis-3 Definition (2016)'''
|-
|-
| '''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]] criteria + suspected infection||Life-threatening organ dysfunction caused by a dysregulated host response to infection, operationalized as:
*[[Hypotension]] with SBP <100 or
*Suspected/documented infection '''PLUS'''
*altered mental status  or
*Increase in [[SOFA]] score by ≥2 points
*Tachypnea (RR >/=22) '''OR'''
*Increase in [[SOFA]] score by 2 points
|-
|-
| '''Severe sepsis'''||*Sepsis +
| '''Severe Sepsis'''||Sepsis + organ dysfunction:
*SBP< 90 or  
*SBP <90, or
*MAP <65 lactate >2 or
*MAP <65, or
*INR >1.5 or
*Lactate >2, or
*Bili>2 or
*INR >1.5, or
*Urine output <0.5ml/kg/h
*Bili >2, or
*Creatinine>2.2 or
*Urine output <0.5 mL/kg/hr, or
*Platelets <100 or
*Creatinine >2.0, or
*SpO@<90%
*Platelets <100, or
||No longer a category
*SpO₂ <90%
||'''No longer a category''' (subsumed into "sepsis," which now requires organ dysfunction by definition)
|-
|-
| '''Septic shock'''||Sepsis + hypotension after adequate fluid resuscitation||Sepsis + vasopressors needed to maintain MAP>65 + lactate >2
| '''Septic Shock'''||Sepsis + hypotension after adequate fluid resuscitation||Sepsis '''PLUS''':
*Vasopressors needed to maintain MAP ≥65 '''AND'''
*Lactate >2 mmol/L (>18 mg/dL) despite adequate volume resuscitation
|}
|}
===qSOFA (Bedside Screening Tool)===
''The [[qSOFA]] was proposed as a bedside screening tool to identify patients outside the ICU who may have sepsis. It is '''not''' the definition of sepsis.''<ref name="seymour"/>
'''SSC 2021 recommends against using qSOFA as a single screening tool for sepsis or septic shock,''' as it has poor sensitivity; however, it may prompt further workup when positive.<ref name="SSC2021"/>


{{QSOFA Score}}
{{QSOFA Score}}
*qSOFA ≥2 should prompt:
**Consideration of possible sepsis
**Initiation of workup (cultures, lactate, imaging)
**Assessment for organ dysfunction (formal [[SOFA]] score)
*A qSOFA <2 does '''not''' rule out sepsis


===[[SOFA]] Score===
===[[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
*The [[SOFA]] score is the formal tool for identifying organ dysfunction in sepsis (increase of ≥2 points = sepsis)<ref name="sepsis3"/>
*Generally used in the ICU; can stratify mortality based on initial score and subsequent changes
*Baseline SOFA score assumed to be 0 in patients without known pre-existing organ dysfunction


===MEDS score===
===MEDS Score===
*The Mortality in Emergency Department Sepsis (MEDS) prediction rule is a proposed method to risk stratify ED patients with sepsis
*The Mortality in Emergency Department Sepsis (MEDS) prediction rule is a proposed method to risk stratify ED patients with sepsis
*Has not gained widespread clinical adoption


===NEWS 2 Score===
===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>
*National Early Warning Score (NEWS) 2 determines degree of illness 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
*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
*Not reliable in spinal cord injury patients due to disturbance of autonomic responses
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**Respiratory rate
**Respiratory rate
**Presence of hypercapnic respiratory failure
**Presence of hypercapnic respiratory failure
**Presence of supplemental O2
**Presence of supplemental O₂
**Temperature
**Temperature
**SBP
**SBP
**Pulse rate
**Pulse rate
**Consciouness
**Consciousness (AVPU scale)
*See below for MDCalc link
*See below for MDCalc link


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==Clinical Features==
==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.''<ref name="sepsis3"/>
*[[Hypotension]] with SBP <100 or
*Suspected infection with evidence of new organ dysfunction ([[SOFA]] increase ≥2), which may manifest as:
*[[Altered mental status]] or
**[[Hypotension]]
*[[Tachypnea]] (RR >/=22) '''OR'''
**[[Altered mental status]]
*Increase in SOFA score by 2 points
**[[Tachypnea]]
**[[Acute kidney injury|Oliguria]]
**Coagulopathy
**Elevated [[lactate]]
**[[Hypoxia]]
**Ileus


===[[Septic shock]]===
===[[Septic shock]]===
Patients with sepsis and any of the following:<ref name="sepsis definition"></ref>
Patients with sepsis and '''both''' of the following despite adequate volume resuscitation:<ref name="sepsis3"/>
#[[Vasopressors|Vasopressor]] requirement to maintain a mean arterial pressure > 65 mm Hg  
#[[Vasopressors|Vasopressor]] requirement to maintain a mean arterial pressure ≥65 mm Hg '''AND'''
#Serum [[lactate]] level greater than 2 mmol/L (>18mg/dL) in the absence of [[hypovolemia]].
#Serum [[lactate]] level >2 mmol/L (>18 mg/dL)


==Differential Diagnosis==
==Differential Diagnosis==
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*CBC
*CBC
*[[Urinalysis]]/Urine culture
*[[Urinalysis]]/Urine culture
*[[Blood culture]]
*[[Blood culture]] (at least 2 sets, ideally before antibiotics but should '''not''' delay antibiotic administration)
*[[CXR]]
*[[CXR]]
*Chem
*Chem (BMP)
*[[LFTs]]
*[[LFTs]]
*Lipase
*Lipase
*[[VBG]]
*[[VBG]] or [[ABG]]
*[[Lactate]]
*[[Lactate]] (re-measure within 2-4 hours if initially elevated)<ref name="SSC2021"/>
*Coags
*Coags
*Consider:
*Consider:
**[[Procalcitonin]]
**[[Procalcitonin]] (may help guide de-escalation of antibiotics; should '''not''' be used to withhold initial empiric antibiotics)
**[[DIC]] panel (fibrinogen, [[D-dimer]], FDP)
**[[DIC]] panel (fibrinogen, [[D-dimer]], FDP)
**T&S
**T&S
**[[CT head]] and/or [[LP]
**[[CT head]] and/or [[LP]]
**TSH ([[thyroid storm]])
**TSH ([[thyroid storm]])
**Cosyntropin stim vs. random cortisol (adrenal insufficiency)
**Cosyntropin stim vs. random cortisol ([[adrenal insufficiency]])
**Pelvic exam ([[toxic shock syndrome]], tampon)  
**Pelvic exam ([[toxic shock syndrome]], tampon)  
**[[Influenza]] rapid testing  
**[[Influenza]] and respiratory viral testing
**CT Abd/Pelvis (abscess, other)
**CT Abd/Pelvis (abscess, other intra-abdominal source)
**spine imaging ([[epidural abscess]], other)
**Spine imaging ([[epidural abscess]], other)


==Time Specific Management==
==Management==
''Time of presentation is defined as the time of triage in the emergency department''
===Hour-1 Bundle===
===3 hour goals<ref name="suriving sepsis update">Surviving Sepsis Updated Bundles in Response to New Evidence [http://emcrit.org/wp-content/uploads/2015/04/SSC_Bundle.pdf full text]</ref>===
''Time zero is the time of triage in the emergency department or the earliest documentation of sepsis-consistent elements. Sepsis and septic shock are medical emergencies; treatment and resuscitation should begin immediately.''<ref name="SSC2021"/>
*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<ref name="suriving sepsis update"></ref>===
The Hour-1 Bundle should be viewed as a quality improvement target. Ideally all interventions begin in the first hour, though they may not all be completed within that time:
*Apply [[vasopressors]] (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) ≥65mmHg
#'''Measure [[lactate]] level''' (re-measure within 2-4 hours if initial lactate >2 mmol/L)
*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:
#'''Obtain [[blood cultures]]''' prior to administration of antibiotics (but do not delay antibiotics to obtain cultures)
**Option 1: Focused Exam
#'''Administer broad-spectrum [[antibiotics]]''' (see timing below)
***Vital signs
#'''Begin rapid administration of 30 mL/kg crystalloid''' for hypotension or lactate ≥4 mmol/L
***Cardiopulmonary Exam
#'''Apply [[vasopressors]]''' if patient is hypotensive during or after fluid resuscitation to maintain MAP ≥65 mmHg
***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 [[Ultrasound: In Shock and Hypotension|cardiovascular ultrasound]]
***Dynamic assessment of fluid responsiveness with passive leg raise or fluid challenge


''A central line and measurement of ScvO<sub>2</sub> is not required and does not impact mortality<ref>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 [[EBQ:ProCESS_Trial|Full Text]] </ref><ref>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</ref><ref>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</ref>
===Antibiotic Timing (SSC 2021)===
''Timing is stratified by presence of shock and likelihood of infection:''<ref name="SSC2021"/>
{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Clinical Scenario'''
| align="center" style="background:#f0f0f0;"|'''Antibiotic Timing'''
|-
| '''Septic shock''' or '''high likelihood of sepsis'''||'''Immediately, ideally within 1 hour''' of recognition (strong recommendation)
|-
| '''Possible sepsis without shock'''||Rapid assessment of infectious vs. non-infectious causes; '''within 3 hours''' if concern for infection persists (weak recommendation)
|-
| '''Alternative non-infectious diagnosis identified'''||Reassess; '''discontinue empiric antibiotics''' if infection is not confirmed<ref name="SSC2021"/>
|}


==Circulation Managment==
*See [[Initial Antibiotics in Sepsis (Main)]] for regimen selection
*Initial choice dependent on suspected source, local antibiogram, and severity of illness
*'''Prolonged (extended/continuous) infusions of beta-lactam antibiotics''' are suggested for maintenance therapy over conventional bolus infusions<ref name="SSC2021"/>
*Perform '''daily reassessment for antimicrobial de-escalation'''<ref name="SSC2021"/>
 
===Source Control===
*Identify and control the source of infection as soon as medically and logistically practical, ideally within 6-12 hours<ref name="SSC2021"/>
*Remove any infected lines or devices
*Drain [[abscesses]]
*Consult surgery or other specialists if indicated (e.g. for [[appendicitis]], [[cholangitis]], [[necrotizing fasciitis]], etc.)
*Prolonged efforts at medical stabilization should '''not''' delay source control in severely ill patients
 
==Circulation Management==
===[[IVF]]===
===[[IVF]]===
*Guidelines recommend initial 30 cc/kg bolus (generally 2L in average adult)
*SSC 2021 '''suggests''' (downgraded from ''recommends'' in 2016) initial 30 mL/kg crystalloid for sepsis-induced hypoperfusion or septic shock, to be given within the first 3 hours<ref name="SSC2021"/>
*Reassess patient's volume status after initial bolus. Auscultate for pulmonary edema. Evaluate peripheral circulation. Consider IVC ultrasound
**This is a starting point; some patients will need more, some less
*Septic patients can be euvolemic but remain hypotensive due to vasodilation. Consider early vasopressors.
**'''Reassess after each bolus''' — do not reflexively give the full 30 mL/kg without clinical reassessment
*Increasing evidence that excessive fluid resuscitation can be harmful.
*'''Balanced crystalloids''' (e.g. [[Lactated Ringer's]]) are suggested over 0.9% [[normal saline]] (weak recommendation)<ref name="SSC2021"/>
**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>
*Use '''dynamic measures''' to guide ongoing fluid resuscitation (suggested over physical exam or static parameters alone):<ref name="SSC2021"/>
**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>
**Passive leg raise with assessment of stroke volume/cardiac output
**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>
**Fluid challenge with reassessment of hemodynamic response
**Stroke volume variation, pulse pressure variation
**Bedside [[Ultrasound: In Shock and Hypotension|cardiovascular ultrasound]] ([[IVC ultrasound]])
*'''Capillary refill time''' can be used to guide resuscitation as an adjunct to other measures<ref name="SSC2021"/>
*'''Lactate-guided resuscitation:''' Suggest targeting a decrease in lactate (re-measure q2-4h) as a marker of tissue perfusion<ref name="SSC2021"/>
*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 (i.e. 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
*Consider assessing [[diastolic dysfunction]] via echo in [[CHF]] patients in whom IVC [[ultrasound]] is not reliable
*'''CVP targets (>8 cmH₂O non-intubated, >12 cmH₂O intubated) are no longer recommended''' as resuscitation endpoints<ref name="SSC2021"/>


''A central line and measurement of ScvO₂ is not required and does not impact mortality''<ref>ProCESS Investigators, Yealy DM, Kellum JA, Juang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370(18):1683-1693. [[EBQ:ProCESS_Trial|Full Text]]</ref><ref>The ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371:1496-1506.</ref><ref>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.</ref>


===[[Pressors]]===
===[[Pressors]]===
*Indicated if MAP<60 despite adequate IVF or if IVF are contraindicated
*Indicated if MAP <65 despite initial fluid resuscitation, or if fluid resuscitation is contraindicated/unlikely to be sufficient
*Best if given when the vascular space is filled; ok if it is not
*'''Vasopressors may be started peripherally''' while central access is being obtained — do not delay initiation to place a central line<ref name="SSC2021"/>
*Target MAP ≥65 mmHg (SSC 2021 recommends an initial target of 65 mmHg '''over''' higher MAP targets)<ref name="SSC2021"/>
 
'''Options:'''
'''Options:'''
*[[Norepinephrine]] (5-20mcg/min) - 1st line<ref>[[EBQ:SOAP II Trial]]</ref>
*'''[[Norepinephrine]]''' (0.1-1 mcg/kg/min, typical starting dose 5-20 mcg/min) — '''1st line'''<ref>[[EBQ:SOAP II Trial]]</ref><ref name="SSC2021"/>
*[[Epinephrine]] (1-20 mcg/min) - 2nd line
*'''[[Vasopressin]]''' (0.03 units/min fixed dose) — '''2nd line''', added to norepinephrine rather than escalating NE above 0.25-0.5 mcg/kg/min<ref name="SSC2021"/>
*[[Vasopressin]] (0.03 units/minute fixed dose) can be added to norepinephrine (NE)
**SSC 2021 suggests adding vasopressin '''before''' epinephrine
**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>
**May reduce the risk of atrial fibrillation compared to catecholamine-only regimens<ref>McIntyre WF, Um KJ, Alhazzani W, et al. Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock. JAMA. 2018;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)
*'''[[Epinephrine]]''' (1-20 mcg/min) — '''3rd line''', added to norepinephrine + vasopressin if MAP target not achieved<ref name="SSC2021"/>
**Do not use Low-dose [[dopamine]] for renal protection
*'''[[Dopamine]]''' — should be used hesitantly and only in highly selected patients (e.g. patients with low risk of tachyarrhythmias and absolute or relative bradycardia)
**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>  
**Do '''not''' use low-dose dopamine for renal protection
*''[[Phenylephrine]] should not be used for treating septic shock except if:
**Dopamine may have increased mortality rates compared to other vasopressors, especially in the pediatric septic patient<ref>Ventura AM, Shieh HH, Bousso A, 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:
**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 (limited evidence)
*[[Methylene blue]] consideration for septic shock refractory to catecholaminergic pressors


===[[Vasopressors|Inotropes]]===
===[[Vasopressors|Inotropes]]===
*[[Dobutamine]] (2-20mcg/kg/min) may be added if:  
*'''[[Dobutamine]]''' (2-20 mcg/kg/min) may be added if:  
**Myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output
**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
**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
**Note: Beta-2 agonism causes vasodilation; therefore needs to be used in conjunction with vasopressors


===[[Steroids]]===
===[[Steroids]]===
*Reasonable to initiate in septic shock in those without contraindications (ex. immunosuppression, wound healing issues, DKA, etc)
*SSC 2021 '''suggests IV corticosteroids''' for adults with septic shock and an ongoing requirement for vasopressor therapy (weak recommendation)<ref name="SSC2021"/>
**While stress dose steroids may shorten recovery time, they have NOT been consistently shown to decrease mortality
*The '''2024 SCCM Focused Update''' further clarifies:<ref name="SCCM2024">Chaudhuri D, Nei AM, Rochwerg B, et al. 2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia. Crit Care Med. 2024;52(5):e219-e233.</ref>
**Consider dosing [[hydrocortisone]] 200 mg IV daily, separated into 2-4 times a day
**'''Suggests''' corticosteroids for adults with septic shock (conditional recommendation, low certainty)
**Do not administer steroids for the treatment of sepsis in the absence of [[shock]]
**'''Recommends against''' high-dose/short-duration corticosteroids (>400 mg/day hydrocortisone equivalent for <3 days) (strong recommendation, moderate certainty)
*Evidence
*'''Dosing:''' [[Hydrocortisone]] 200 mg IV daily, divided q6h (50 mg q6h) or as continuous infusion
**ADRENAL trial showed that stress dose steroids is associated with faster time to shock resolution and discharge from ICU<ref>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.</ref>
*Do '''not''' administer steroids for treatment of sepsis in the '''absence of shock'''
**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<ref>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.</ref>
*Stress dose steroids are associated with faster time to shock resolution and faster ICU discharge<ref>Venkatesh B, Finfer S, Cohen J, et al; ADRENAL Trial Investigators. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med. 2018;378(9):797-808.</ref>
**Newer meta-analyses do not show an increased incidence of superinfections related to initiation of stress dose steroids<ref>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.</ref>
*While stress dose steroids shorten recovery time, they have '''not''' been consistently shown to decrease overall mortality (though meta-analyses suggest a possible small benefit)<ref name="SCCM2024"/>
*Addition of fludrocortisone may not make a difference as hydrocortisone has both adrenocorticoid and mineralocorticoid effects
*Newer meta-analyses do not show an increased incidence of superinfections related to initiation of stress dose steroids<ref>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.</ref>
*ACTH cosyntropin testing likely unreliable in critically ill patients
*Addition of fludrocortisone likely unnecessary as hydrocortisone has both glucocorticoid and mineralocorticoid effects
*Steroids are associated with adverse effects such as hyperglycemia, hypernatremia, and neuromuscular weakness. Weight risks and benefits<ref>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.</ref>
*ACTH cosyntropin testing is likely unreliable in critically ill patients and should '''not''' guide the decision to give steroids
*Steroids are associated with adverse effects including hyperglycemia, hypernatremia, and neuromuscular weakness; weigh risks and benefits<ref>Pitre T, Drover K, Chaudhuri D, et al. Corticosteroids in Sepsis and Septic Shock: A Systematic Review, Pairwise, and Dose-Response Meta-Analysis. Crit Care Explor. 2024;6(1):e1000.</ref>


===[[Esmolol]]===
===[[Esmolol]]===
*One open-label, 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>
*One open-label, 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
*All patients were fluid resuscitated, intubated, given hydrocortisone 300 mg/day
*Will require further multi-center RCTs to confirm findings
*'''Not standard of care''' — will require further multi-center RCTs to confirm findings; this result has not been replicated
 
==Infection Control==
===Source control===
*Remove any infected lines
*Drain [[abscesses]]
*Consult surgery or other specialists if indicated (e.g. for [[appendicitis]], [[cholangitis]], etc.)
 
===[[Antibiotics]]===
*Administer within 3 hours
*Initial choice dependant on suspected source, local antibiogram, and severity of illness
*See [[Initial Antibiotics in Sepsis (Main)]]


==[[Blood Products]]==
==[[Blood Products]]==
===[[RBCs]]===
===[[RBCs]]===
Only transfuse RBCs when hemoglobin decreases to <7.0 g/dL (goal is 7.0 –9.0 g/dL in adults)  
*Only transfuse RBCs when hemoglobin decreases to <7.0 g/dL (target 7.0–9.0 g/dL in adults)<ref name="SSC2021"/>
===Erythropoietin===
===Erythropoietin===
Do not use erythropoietin as a specific treatment of anemia associated with severe sepsis  
*Do not use erythropoietin as a specific treatment of anemia associated with severe sepsis  
===[[Platelets]]===
===[[Platelets]]===
*In severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 x 10<sup>9</sup>/L) in the absence of apparent bleeding
*In severe sepsis, administer platelets prophylactically when counts are <10,000/mm³ (10 × 10⁹/L) in the absence of apparent bleeding
*If < 20,000/mm3 (20 x 10<sup>9</sup>/L) and significant risk of bleeding then administer platelets.
*If <20,000/mm³ (20 × 10⁹/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 × 10⁹/L) if there is active bleeding, planned surgery, or other procedures


==Disposition==
==Disposition==
*Admit, possibly to step-down or ICU
*Admit, likely to step-down or ICU
*SSC 2021 suggests admitting patients with sepsis or septic shock who require ICU care '''within 6 hours''' of identification<ref name="SSC2021"/>


==External Links==
==External Links==
Line 217: Line 250:
*[https://www.mdcalc.com/national-early-warning-score-news-2#evidence MDCalc - NEWS 2]
*[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]
*[https://journals.lww.com/ccmjournal/fulltext/2021/11000/surviving_sepsis_campaign__international.21.aspx SSC 2021 Guidelines (Full Text)]


==See Also==
==See Also==
Line 223: Line 257:
*[[EBQ:ProCESS Trial]]
*[[EBQ:ProCESS Trial]]
*[[Quick Sequential (Sepsis Related) Organ Failure Assessment Score (qSOFA)]]
*[[Quick Sequential (Sepsis Related) Organ Failure Assessment Score (qSOFA)]]
*[[Pneumonia (main)]]


==References==
==References==
<references/>
{{reflist|2}}
 


[[Category:ID]]
[[Category:ID]]
[[Category:Critical Care]]
[[Category:Critical Care]]

Revision as of 16:25, 8 March 2026

This page is for adult patients. For pediatric patients, see: Sepsis (peds)

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]
  • The most common primary sources of infection resulting in sepsis are the lungs, the abdomen, and the urinary tract[3]
  • Sepsis and septic shock are major healthcare problems, killing between one in three and one in six of those affected[4]
  • In-hospital mortality for septic shock is approximately 30-40%[4]
  • Positive cultures are not obligatory in the diagnosis of sepsis
  • Pneumonia, intra-abdominal infections, and pyelonephritis are the most common primary causes

Sepsis-3 Definitions (2016)

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

Old Definition Sepsis-3 Definition (2016)
Sepsis 2 SIRS criteria + suspected infection Life-threatening organ dysfunction caused by a dysregulated host response to infection, operationalized as:
  • Suspected/documented infection PLUS
  • Increase in SOFA score by ≥2 points
Severe Sepsis Sepsis + organ dysfunction:
  • SBP <90, or
  • MAP <65, or
  • Lactate >2, or
  • INR >1.5, or
  • Bili >2, or
  • Urine output <0.5 mL/kg/hr, or
  • Creatinine >2.0, or
  • Platelets <100, or
  • SpO₂ <90%
 No longer a category (subsumed into "sepsis," which now requires organ dysfunction by definition)
Septic Shock Sepsis + hypotension after adequate fluid resuscitation Sepsis PLUS:
  • Vasopressors needed to maintain MAP ≥65 AND
  • Lactate >2 mmol/L (>18 mg/dL) despite adequate volume resuscitation

qSOFA (Bedside Screening Tool)

The qSOFA was proposed as a bedside screening tool to identify patients outside the ICU who may have sepsis. It is not the definition of sepsis.[5]

SSC 2021 recommends against using qSOFA as a single screening tool for sepsis or septic shock, as it has poor sensitivity; however, it may prompt further workup when positive.[4]

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)
  • qSOFA ≥2 should prompt:
    • Consideration of possible sepsis
    • Initiation of workup (cultures, lactate, imaging)
    • Assessment for organ dysfunction (formal SOFA score)
  • A qSOFA <2 does not rule out sepsis

SOFA Score

  • The SOFA score is the formal tool for identifying organ dysfunction in sepsis (increase of ≥2 points = sepsis)[1]
  • Generally used in the ICU; can stratify mortality based on initial score and subsequent changes
  • Baseline SOFA score assumed to be 0 in patients without known pre-existing organ dysfunction

MEDS Score

  • The Mortality in Emergency Department Sepsis (MEDS) prediction rule is a proposed method to risk stratify ED patients with sepsis
  • Has not gained widespread clinical adoption

NEWS 2 Score

  • National Early Warning Score (NEWS) 2 determines degree of illness 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
    • Consciousness (AVPU scale)
  • 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.[1]

Septic shock

Patients with sepsis and both of the following despite adequate volume resuscitation:[1]

  1. Vasopressor requirement to maintain a mean arterial pressure ≥65 mm Hg AND
  2. Serum lactate level >2 mmol/L (>18 mg/dL)

Differential Diagnosis

Shock


Adrenal crisis

Evaluation

Work-Up

Management

Hour-1 Bundle

Time zero is the time of triage in the emergency department or the earliest documentation of sepsis-consistent elements. Sepsis and septic shock are medical emergencies; treatment and resuscitation should begin immediately.[4]

The Hour-1 Bundle should be viewed as a quality improvement target. Ideally all interventions begin in the first hour, though they may not all be completed within that time:

  1. Measure lactate level (re-measure within 2-4 hours if initial lactate >2 mmol/L)
  2. Obtain blood cultures prior to administration of antibiotics (but do not delay antibiotics to obtain cultures)
  3. Administer broad-spectrum antibiotics (see timing below)
  4. Begin rapid administration of 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L
  5. Apply vasopressors if patient is hypotensive during or after fluid resuscitation to maintain MAP ≥65 mmHg

Antibiotic Timing (SSC 2021)

Timing is stratified by presence of shock and likelihood of infection:[4]

Clinical Scenario Antibiotic Timing
Septic shock or high likelihood of sepsis Immediately, ideally within 1 hour of recognition (strong recommendation)
Possible sepsis without shock Rapid assessment of infectious vs. non-infectious causes; within 3 hours if concern for infection persists (weak recommendation)
Alternative non-infectious diagnosis identified Reassess; discontinue empiric antibiotics if infection is not confirmed[4]
  • See Initial Antibiotics in Sepsis (Main) for regimen selection
  • Initial choice dependent on suspected source, local antibiogram, and severity of illness
  • Prolonged (extended/continuous) infusions of beta-lactam antibiotics are suggested for maintenance therapy over conventional bolus infusions[4]
  • Perform daily reassessment for antimicrobial de-escalation[4]

Source Control

  • Identify and control the source of infection as soon as medically and logistically practical, ideally within 6-12 hours[4]
  • Remove any infected lines or devices
  • Drain abscesses
  • Consult surgery or other specialists if indicated (e.g. for appendicitis, cholangitis, necrotizing fasciitis, etc.)
  • Prolonged efforts at medical stabilization should not delay source control in severely ill patients

Circulation Management

IVF

  • SSC 2021 suggests (downgraded from recommends in 2016) initial 30 mL/kg crystalloid for sepsis-induced hypoperfusion or septic shock, to be given within the first 3 hours[4]
    • This is a starting point; some patients will need more, some less
    • Reassess after each bolus — do not reflexively give the full 30 mL/kg without clinical reassessment
  • Balanced crystalloids (e.g. Lactated Ringer's) are suggested over 0.9% normal saline (weak recommendation)[4]
  • Use dynamic measures to guide ongoing fluid resuscitation (suggested over physical exam or static parameters alone):[4]
    • Passive leg raise with assessment of stroke volume/cardiac output
    • Fluid challenge with reassessment of hemodynamic response
    • Stroke volume variation, pulse pressure variation
    • Bedside cardiovascular ultrasound (IVC ultrasound)
  • Capillary refill time can be used to guide resuscitation as an adjunct to other measures[4]
  • Lactate-guided resuscitation: Suggest targeting a decrease in lactate (re-measure q2-4h) as a marker of tissue perfusion[4]
  • Increasing evidence that excessive fluid resuscitation can be harmful:
    • Positive fluid balance on day 3 of hospital admission independently associated with increasing mortality[8]
    • Protocolized fluid administration (i.e. traditional Early Goal Directed Therapy) has no mortality benefit over usual care[9][10]
    • High volume (5+ L) resuscitation associated with increased mortality[11]
  • Consider assessing diastolic dysfunction via echo in CHF patients in whom IVC ultrasound is not reliable
  • CVP targets (>8 cmH₂O non-intubated, >12 cmH₂O intubated) are no longer recommended as resuscitation endpoints[4]

A central line and measurement of ScvO₂ is not required and does not impact mortality[12][13][14]

Pressors

  • Indicated if MAP <65 despite initial fluid resuscitation, or if fluid resuscitation is contraindicated/unlikely to be sufficient
  • Vasopressors may be started peripherally while central access is being obtained — do not delay initiation to place a central line[4]
  • Target MAP ≥65 mmHg (SSC 2021 recommends an initial target of 65 mmHg over higher MAP targets)[4]

Options:

  • Norepinephrine (0.1-1 mcg/kg/min, typical starting dose 5-20 mcg/min) — 1st line[15][4]
  • Vasopressin (0.03 units/min fixed dose) — 2nd line, added to norepinephrine rather than escalating NE above 0.25-0.5 mcg/kg/min[4]
    • SSC 2021 suggests adding vasopressin before epinephrine
    • May reduce the risk of atrial fibrillation compared to catecholamine-only regimens[16]
  • Epinephrine (1-20 mcg/min) — 3rd line, added to norepinephrine + vasopressin if MAP target not achieved[4]
  • Dopamine — should be used hesitantly and only in highly selected patients (e.g. 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[17]
  • 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
  • Methylene blue — consideration for septic shock refractory to catecholaminergic pressors (limited evidence)

Inotropes

  • Dobutamine (2-20 mcg/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
    • Note: Beta-2 agonism causes vasodilation; therefore needs to be used in conjunction with vasopressors

Steroids

  • SSC 2021 suggests IV corticosteroids for adults with septic shock and an ongoing requirement for vasopressor therapy (weak recommendation)[4]
  • The 2024 SCCM Focused Update further clarifies:[18]
    • Suggests corticosteroids for adults with septic shock (conditional recommendation, low certainty)
    • Recommends against high-dose/short-duration corticosteroids (>400 mg/day hydrocortisone equivalent for <3 days) (strong recommendation, moderate certainty)
  • Dosing: Hydrocortisone 200 mg IV daily, divided q6h (50 mg q6h) or as continuous infusion
  • Do not administer steroids for treatment of sepsis in the absence of shock
  • Stress dose steroids are associated with faster time to shock resolution and faster ICU discharge[19]
  • While stress dose steroids shorten recovery time, they have not been consistently shown to decrease overall mortality (though meta-analyses suggest a possible small benefit)[18]
  • Newer meta-analyses do not show an increased incidence of superinfections related to initiation of stress dose steroids[20]
  • Addition of fludrocortisone likely unnecessary as hydrocortisone has both glucocorticoid and mineralocorticoid effects
  • ACTH cosyntropin testing is likely unreliable in critically ill patients and should not guide the decision to give steroids
  • Steroids are associated with adverse effects including hyperglycemia, hypernatremia, and neuromuscular weakness; weigh risks and benefits[21]

Esmolol

  • One open-label, single-center RCT showing ~40% reduction in mortality when esmolol paired with norepinephrine infusion, with goal HR 80-95 BPM[22]
  • All patients were fluid resuscitated, intubated, given hydrocortisone 300 mg/day
  • Not standard of care — will require further multi-center RCTs to confirm findings; this result has not been replicated

Blood Products

RBCs

  • Only transfuse RBCs when hemoglobin decreases to <7.0 g/dL (target 7.0–9.0 g/dL in adults)[4]

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 × 10⁹/L) in the absence of apparent bleeding
  • If <20,000/mm³ (20 × 10⁹/L) and significant risk of bleeding, then administer platelets
  • <50,000/mm³ (50 × 10⁹/L) if there is active bleeding, planned surgery, or other procedures

Disposition

  • Admit, likely to step-down or ICU
  • SSC 2021 suggests admitting patients with sepsis or septic shock who require ICU care within 6 hours of identification[4]

External Links

See Also

References

  1. ↑ 1.0 1.1 1.2 1.3 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. ↑ 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.
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 4.20 4.21 4.22 4.23 Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021;49(11):e1063-e1143.
  5. ↑ 5.0 5.1 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. ↑ 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.
  9. ↑ 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
  10. ↑ 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
  11. ↑ 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
  12. ↑ ProCESS Investigators, Yealy DM, Kellum JA, Juang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370(18):1683-1693. Full Text
  13. ↑ The ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371:1496-1506.
  14. ↑ 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.
  15. ↑ EBQ:SOAP II Trial
  16. ↑ McIntyre WF, Um KJ, Alhazzani W, et al. Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock. JAMA. 2018;319(18):1889.
  17. ↑ Ventura AM, Shieh HH, Bousso A, 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.
  18. ↑ 18.0 18.1 Chaudhuri D, Nei AM, Rochwerg B, et al. 2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia. Crit Care Med. 2024;52(5):e219-e233.
  19. ↑ Venkatesh B, Finfer S, Cohen J, et al; ADRENAL Trial Investigators. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med. 2018;378(9):797-808.
  20. ↑ 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.
  21. ↑ Pitre T, Drover K, Chaudhuri D, et al. Corticosteroids in Sepsis and Septic Shock: A Systematic Review, Pairwise, and Dose-Response Meta-Analysis. Crit Care Explor. 2024;6(1):e1000.
  22. ↑ 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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