Shock and Sepsis
Shock — most frequently caused by sepsis — is a common reason for ICU admission because of the need for close hemodynamic monitoring and nursing care. Patients with septic shock can be some of the sickest that you’ll encounter during residency, and the complexities of management can seem overwhelming. In this section, we’ll cover the basics of:
Shock is defined as a state of tissue hypoxia due to decreased or dysregulated oxygen delivery or extraction resulting in end-organ damage. Clinical manifestations include:
- systemic arterial hypotension: in adults, typically SBP <90 mm Hg or mean arterial pressure (MAP) <70 mm Hg where MAP = (1/3) x SBP + (2/3) x DBP
- clinical signs of tissue hypoperfusion: cool and clammy skin versus warm and flushed, low urine output (<0.5 mL/kg/hr), altered mental status
- metabolic acidosis: serum lactate level >2 mmol/liter, possible elevated anion gap
Causes and Pathophysiology
Mean arterial pressure is the product of cardiac output (CO) multiplied by systemic vascular resistance (SVR); therefore, shock can be due to a decrease in SVR, CO, or both (see figure below for more details).
Septic shock, which is a form of distributive shock, is the most common etiology of shock in the ICU. However, other etiologies should be considered in the differential diagnosis. The four mechanisms listed in the table below are not mutually exclusive; for example, patients with sepsis commonly have myocardial depression that improves with resolution of sepsis.
Causes of Shock Classified by Mechanism and Hemodynamics
||Differential Diagnosis (examples)
||Primary Hemodynamic ∆
||Hemorrhage, internal fluid losses (third-spacing), external fluid losses (GI losses)
||Pulmonary embolism, cardiac tamponade, or tension pneumothorax
||Acute myocardial infarction, end-stage cardiomyopathy, advanced valvular heart disease, myocarditis, cardiac arrhythmias, pump failure or dysfunction
Abbreviations: SVR, systemic vascular resistance; CO, cardiac output
Initial Assessment of Shock States
Treat the underlying cause: Identifying the etiology of shock is crucial for adequate treatment. Each of the diagnoses listed in the table above requires a specific management strategy. For example:
- anaphylactic shock (a form of distributive shock): IV epinephrine, identification of the cause of anaphylaxis and its removal
- septic shock (a form of distributive shock): broad spectrum IV antibiotics
- hemorrhagic shock: massive transfusion of blood products, definite hemostasis
- pulmonary embolism: systemic thrombolysis or embolectomy
- cardiogenic shock: percutaneous coronary intervention for myocardial infarction, inotropes, and sometimes mechanical support (e.g., intra-aortic balloon pump, percutaneous left ventricular assist device, venoarterial ECMO)
- Patients with distributive, hypovolemic, and obstructive shock should be given IV fluid resuscitation prior to initiation of vasopressors. Use objective measures to assess how much and when to give more fluids (see Resuscitation Fluids and Transfusion in this rotation guide for more information).
- Typically, vasopressors are titrated to a mean arterial pressure of 65 mm Hg, although decreasing lactate level and improving urine output are reassuring signs of adequate organ perfusion.
- Inotropes may be indicated in the treatment of cardiogenic shock from primary pump failure.
- The table below summaries commonly used vasopressors and inotropes (see Inotropes and Vasopressors for more information).
Commonly Used Vasopressors and Inotropes for the Treatment of Shock
||Notes and Adverse Effects (AE)
|α1 >> β1 > β2
Usually first choice pressor
AE: Arrhythmias, peripheral (digital) ischemia
Useful in tachyarrhythmias
AE: Reflex bradycardia,
severe peripheral & visceral vasoconstriction
|V1 , V2
Add to norepinephrine in septic shock (VASST trial)
AE: Arrhythmias, cardiac ischemia,
peripheral & splanchnic vasoconstriction
|α1 > β1 > β2
First line for anaphylaxis and cardiac arrest
AE: Ventricular arrhythmias, cardiac ischemia
|D1 >> β1 > α1 > β2
mild ↑ SVR
|AE: Ventricular arrhythmias, cardiac ischemia,
||β1 >> β2 > α1
Inotrope, not vasopressor
Can cause hypotension
AE: Ventricular arrhythmias, cardiac ischemia
Use with caution in patients with renal impairment
AE: Hypotension, ventricular arrhythmias
α1 = alpha adrenergic receptors, β1 and β2 = beta adrenergic receptors, V1 and V2 = vasopressin receptors, D1 = dopamine receptor; CO = cardiac output; HR = heart rate; SVR = systemic vascular resistance
*Receptor binding is shown for physiologic concentrations
(Adapted from: Inotropes and Vasopressors. Circulation 2008.)
Sepsis and Septic Shock
Although sepsis has long been recognized as a systemic syndrome, precisely defining it has been challenging.
- In 1992, an international consensus conference introduced the term systemic inflammatory response syndrome (SIRS) and defined sepsis, severe sepsis, and septic shock (see table below).
- In 2003, a second international conference reaffirmed the definitions and acknowledged that SIRS may be nonspecific. (More-recent research suggests that SIRS-negative sepsis also is associated with high mortality and that the ≥2 criteria cut-off does not represent a transition in mortality.) The second group offered additional criteria to consider for diagnosing sepsis.
- In 2016, a third international conference defined sepsis (Sepsis-3) as life-threatening organ dysfunction caused by a dysregulated host response to infection.
Sepsis and Septic Shock Definitions
||≥2 of the following:
1. temperature >38°C or <36°C
2. heart rate >90 beats per min
3. respiratory rate >20 breaths per min or PaCO2 <32 mm Hg
4. WBC >12,000 or <4000 or >10% bands
|No longer used
||SIRS and documented infection
||Organ dysfunction as defined by an
increase of ≥2 points in total SOFA score
||Sepsis with organ dysfunction, hypoperfusion
(e.g., lactic acidosis, oliguria, altered mental
status), or hypotension
|No longer used (considered redundant
because sepsis is now defined by organ
||Severe sepsis and unexplained hypotension
(SBP <90 mm Hg or 40 mm Hg reduction from
baseline) despite adequate fluid resuscitation
or requiring inotropic or vasopressor agents
|Sepsis with hypotension requiring
vasopressors to maintain MAP ≥65 mm Hg
and having a serum lactate level >2 mmol/L
despite adequate volume resuscitation
Abbreviations: SIRS, systemic inflammatory response syndrome; PaCO2, partial pressure of arterial carbon dioxide; WBC, white blood cell; SBP, systolic blood pressure; SOFA, sequential organ failure assessment; MAP, mean arterial pressure
To address the poor specificity of SIRS, the new definition shifts identification away from SIRS to the Sequential Organ Failure Assessment (SOFA, range 0–24, with higher scores indicating more-severe illness). The new definitions of sepsis and septic shock were based on studies and review of the literature for factors that best predicted mortality. Since publication, the 2016 definition has been criticized for the difficulty of incorporating into practice.
Because SOFA requires laboratory values and may be less predictive in patients outside of the ICU, a “quick” SOFA (qSOFA) was developed to identify patients with likely sepsis at the bedside. Having ≥2 of the following qSOFA criteria in the setting of suspected infection has been associated with a greater risk of death or prolonged ICU stay.
- alteration in mental status (Glasgow Coma Score ≤13)
- systolic blood pressure ≤100 mm Hg
- respiratory rate ≥22/min
Until 2001, sepsis was not treated as a medical emergency and the approach to care was variable. In 2001, Dr. Emanuel Rivers studied a strict protocol of early goal-directed therapy (EGDT) for sepsis management, requiring central venous access to measure central venous pressure (CVP) and central venous oxygen saturation (ScvO2) to guide fluid resuscitation, blood transfusions to prespecified goals, and administration of vasopressor drugs. This single-center study showed improved outcomes with EGDT and transformed sepsis care for the next 15 years.
However, concerns about the complex and resource-intensive EGDT led researchers to reexamine the results of the Rivers trial. In 2014 and 2015, three multicenter studies — Protocolized Care for Early Septic Shock (ProCESS), Australian Resuscitation in Sepsis Evaluation (ARISE), and Protocolized Management in Sepsis (ProMISe) — demonstrated that EGDT was not superior to current usual critical care practices, suggesting that a strict protocol of continuous CVP and ScvO2 monitoring does not appear to add any benefit. Note: Between the time of the River’s study and the three trials noted above, the “accepted practice” for patients with sepsis had changed such that patients in ProCESS, ARISE, and ProMISe received early antibiotics and fluids (>30 mL/kg) before randomization, so those principles of EGDT are still very important.
The cornerstones of therapy for patients in septic shock are early initiation of appropriate antibiotics and adequate volume resuscitation.
Early antibiotic therapy:
- In a 2006 study, each hour of delay in delivery of appropriate antibiotics increased mortality by about 7%. These findings were demonstrated again in a 2014 study using data from the Surviving Sepsis Campaign (SCC) database. The SSC recommends administration of effective IV antibiotics within 1 hour of recognizing sepsis or septic shock.
- Antibiotics should target all organisms most likely to cause infection in the suspected organ system; if the source of infection is not yet known, empiric broad-spectrum antibiotics are indicated.
- Crystalloids, such as lactated Ringer’s solution or normal saline, are the fluids of choice for resuscitation.
- Initial fluid challenge should be at ≥30 mL/kg (~2L in a 70-kg adult) for patients with sepsis-induced hypoperfusion.
- Withhold blood transfusions until a patient’s hemoglobin concentration is <7 g/dL, unless there is evidence of bleeding, severe hypoxemia, or myocardial ischemia.
- See Resuscitation Fluids and Transfusion in this rotation guide for more on volume resuscitation.
- Start vasopressors if the patient’s MAP is not responsive to fluid resuscitation.
- The goal MAP on vasopressors typically is ≥65 mm Hg. The 2014 SEPSISPAM trial showed no mortality difference between MAP goals of 65-70 mm Hg vs. 80-85 mm Hg, although among patients with chronic hypertension, those in the higher goal group had less renal-replacement therapy but more atrial fibrillation.
- The safest way to deliver vasopressors is through central venous access (internal jugular, subclavian, femoral catheter, or peripherally inserted central catheter). Subclavian may cause less blood stream infections and more pneumothorax than internal jugular or femoral.
- The SSC recommends norepinephrine as the first-choice vasopressor in septic shock. See the table above for commonly used vasopressors in the medical ICUs.
- Many therapies that have been used in the treatment of septic shock are no longer part of clinical practice because high-quality trials have not shown benefit (and have sometimes shown harm), such as activated protein C, which was initially promising in PROWESS but later disappointing in PROWESS-SHOCK.
- The use of glucocorticoids in sepsis remains controversial. A 2002 French study showed that patients with relative adrenal insufficiency and septic shock had a mortality benefit from hydrocortisone, but this was not replicated by the CORTICUS trial for septic shock and the HYPRESS trial for severe sepsis. In 2018, two larger randomized controlled trials, APROCCHSS and ADRENAL, once again came to different conclusions. Prior to their publication, the SCC suggests not using IV hydrocortisone unless adequate fluid resuscitation and vasopressors are not enough to restore hemodynamics.