Sepsis (Main)

Background

• Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection
• The infection is most commonly by bacteria, but can also be by fungi, viruses, or parasites
• Risk of death from sepsis being as high as 30%, severe sepsis as high as 50%, and septic shock as high as 80%
• The most common primary sources of infection resulting in sepsis are the lungs, the abdomen, and the urinary tract
• Sepsis caries a 40% in hospital mortality

Definition Changes

In 2016 new definitions were adopted for the evaluation and diagnosis of Sepsis, Sever Sepsis and Septic shock

	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: Hypotensionwith 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

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

• ≥2 of 4 criteria must be present:

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

Clinical Features

Sepsis

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

• Hypotensionwith SBP <100 or
• altered mental status or
• Tachypnea (RR >/=22) OR
• Increase in SOFA score by 2 points

Septic shock

Patients with sepsis and any of the following:

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

• Adrenal Insufficiency
• Salicylate Toxicity
• Anticholinergic Toxicity
• Neuroleptic Malignant Syndrome
• Malignant Hyperthermia
• Thyrotoxicosis

Shock

• Cardiogenic
  • Acute valvular Regurgitation/VSD
  • CHF
  • Dysrhythmia
  • ACS
  • Myocardial Contusion
  • Myocarditis
  • Drug toxicity (e.g. beta blocker, CCB, or bupropion OD)
• Obstructive
  • Air embolism
  • Aortic Stenosis
  • Cardiac Tamponade
  • PE
  • Tension pneumothorax
• Distributive
  • Adrenal crisis
  • Anaphylaxis
  • Neurogenic shock
  • Sepsis
  • Toxicologic
• Hypovolemic
  • Severe dehydration
  • Hemorrhagic shock (traumatic and non-traumatic)

Evaluation

Work-Up

• CBC
• Urinalysis/Urine culture
• Blood culture
• CXR
• Chem
• LFT
• Lipase
• VBG
• Lactate
• Procalcitonin
• Coags
• DIC panel (fibrinogen, D-dimer, FDP)
• T&S
• ?CT head/LP
• ?TSH (thyroid storm)
• ?Cosyntropin stim vs. random cortisol (adrenal insufficiency)

Time Specific Management

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

3 hour goals

• 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

• 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:
  • Repeat focused exam OR any 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

Circulation Managment

IVF

• Reassess after each bolus
• Average is 5-6L within first 6 hr
• Positive fluid balance in the first two days of ICU admission is not associated with increased mortality
  • However, positive fluid balance at day 3 of hospital admission is independently associated with increased mortality
• Careful reassessment of volume status is required in in patients with significantly depressed ejection fraction
• 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
• Epinephrine (1-20 mcg/min) - 2nd line
• Vasopressin (0.03 units/minute fixed dose) can be added to norepinephrine (NE)
• 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
• 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
• All patients were fluid resuscitated, intubated, given hydrocortisone 300 mg/day
• Will require further multi-center RCTs to confirm findings

Infection Control

• Source Control
• Remove infected lines, surgery if indicated

Antibiotics

• Administer within 3 hours
• See Initial Antibiotics in Sepsis (Main)

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

• MDCalc - SIRS, Sepsis, and Septic Shock Criteria
• MDCalc - qSOFA Score
• EMCrit Sepsis 3.0

See Also

• Initial Antibiotics in Sepsis (Main)
• Sepsis (Peds)
• EBQ:ProCESS Trial
• Quick Sequential (Sepsis Related) Organ Failure Assessment Score (qSOFA)

References

Authors

Daniel Ostermayer, Jordan Swartz, Yos Yachivev, Ross Donaldson, Vincent Chan, Kevin Lu, Neil Young, Michael Hwang, Daniel Eggeman, Bobak Zonnoor, Greg Armani, Hanno Davel, Claire