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

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)

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

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:

Temperature >38°C (100.4F) or <36°C (96.9F) HR >90 BPM RR >20 breaths/minute or PaCO2 <32 mmHg 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]

Hypotensionwith SBP <100 or

Altered mental status or

Tachypnea (RR >/=22) OR

Increase in SOFA score by 2 points

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

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

Differential Diagnosis

Evaluation

Work-Up

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: 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 ScvO 2 is not required and does not impact mortality[10][11][12]

Circulation Managment

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





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

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



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

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

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)

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

In severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 x 10 9 /L) in the absence of apparent bleeding

/L) in the absence of apparent bleeding If < 20,000/mm3 (20 x 10 9 /L) and significant risk of bleeding then administer platelets.

/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

See Also

References