Systemic Infection and Inflammation

The most significant discovery in critical care in the past 20–30 years is the prominent role played by inflammation in the pathogenesis of multiorgan dysfunction in critically ill patients. This chapter presents four disorders that involve inflammatory injury in major organs: sepsis, septic shock, anaphylaxis, and anaphylactic shock.

I. Clinical Syndromes

A. Systemic Inflammatory Response Syndrome

The inflammatory response is a complex process that is triggered by conditions that threaten the functional integrity of the host. Examples of such conditions include physical injury (trauma), chemical injury (e.g., gastric acid aspiration), oxidant injury (e.g., radiation), thermal injury (burns), and microbial invasion.
The clinical manifestations of the inflammatory response are listed in Table 9.1; the presence of at least two of these findings has been called the systemic inflammatory response syndrome (SIRS) (1).
The diagnosis of SIRS has two limitations that deserve emphasis:
- The presence of SIRS does not indicate the presence of infection; i.e., infection is identified in only 25–50% of patients with SIRS (2,3).
- The presence of SIRS does not always indicate the presence of inflammation; e.g., anxiety can produce tachycardia and tachypnea, which qualifies for the diagnosis of SIRS despite the absence of an inflammatory response.
SIRS is essentially a signal to search for the responsible condition (primarily infection).

Table 9.1 Systemic Inflammatory Response Syndrome (SIRS)


The diagnosis of SIRS requires at least 2 of the following: Temperature >38°C or <36°C Heart rate >90 beats/min Respiratory rate >20 breaths/min, or PaCO₂ <32 mm Hg WBC count >12,000/mm³ or <4000/mm³, or 10% immature neutrophils (band forms)
From Reference 2.

B. Sepsis

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection (4). The organ dysfunction is attributed to inflammatory injury, which is the result of uncontrolled inflammation and/or inadequate host defenses against inflammatory injury.

1. SOFA Score

In patients with a suspected or documented infection, the Sepsis-related Organ Failure Assessment (SOFA) score is recommended for identifying organ dysfunction (4,5). (See Appendix 4 for the SOFA scoring method.)

A change in the baseline SOFA score of ≥2 points is evidence of organ dysfunction, and this condition
has a mortality rate that is 2- to 25-fold higher than the mortality with uncomplicated infections (4).
The baseline SOFA score is assumed to be zero unless the patient has pre-existing organ dysfunction.

2. Quick SOFA Criteria

The SOFA score requires laboratory measurements, which can delay recognition of organ dysfunction, but rapid recognition of organ dysfunction is possible with the Quick SOFA (qSOFA) criteria shown in Table 9.2 (4).

The presence of any two of the qSOFA criteria is presumptive evidence of organ dysfunction (4).
The qSOFA criteria should be used as a screening tool, and a positive result should prompt further evaluation of organ dysfunction (e.g., with the full SOFA score).

Table 9.2 Quick SOFA (qSOFA) Criteria


Sepsis is likely if an infection is accompanied by any 2 of the following conditions: Respiratory Rate ≥22 breaths/min Altered Mentation (Glasgow Coma Score ≤13) Systolic Blood Pressure ≤100 mm Hg
From Reference 4.

C. Septic Shock

Septic shock is a subset of sepsis that is characterized by the following conditions (4):
- Hypotension that is not corrected by volume resuscitation.
- Sustained requirement for a vasopressor to maintain a mean arterial pressure ≥65 mm Hg.
- A serum lactate level >2 mmol/L.
The mortality rate in septic shock is 35–55%, which is much higher than the mortality rate of 10–20% in sepsis (4).

II. Management of Septic Shock

The management of septic shock requires an understanding of the associated changes in hemodynamics and energy metabolism as described next.

A. Pathophysiology

1. Hemodynamic Alterations

Septic shock is characterized by systemic vasodilation involving both arteries and veins, which reduces ventricular preload (from venodilation) and ventricular afterload (from arterial vasodilation). The vascular changes are attributed to the enhanced production of nitric oxide (a vasodilator) in vascular endo-thelial cells (6).
Injury in the vascular endothelium (from neutrophil attachment and degranulation) leads to fluid extravasation and hypovolemia (6), which adds to the reduced cardiac filling from venodilation.
Proinflammatory cytokines promote cardiac dysfunction (both systolic and diastolic dysfunction), however the cardiac output is usually increased as a result of tachycardia and decreased afterload (7).
Despite the increased cardiac output, splanchnic blood flow is typically reduced in septic shock (6). This can lead to disruption of the intestinal mucosa and “translocation” of enteric pathogens and endotoxins across the mucosa and into the systemic circulation.
This, then, can be a source of progressive and unregulated systemic inflammation (which is the source of organ dysfunction in sepsis and septic shock).
In the advanced stages of septic shock, cardiac output begins to decline, eventually resulting in a hemodynamic pattern that resembles cardiogenic shock (i.e., high cardiac filling pressures, low cardiac output, and increased systemic vascular resistance).

2. Cytopathic Hypoxia

As mentioned at the end of Chapter 6 (see Section III-F), the impaired energy metabolism in septic shock is the result of a defect in oxygen utilization in mitochondria (8); a condition known as cytopathic hypoxia (9). Tissue O₂ levels are not reduced, and can actually be increased (10).
Since tissue O₂ levels are not impaired in septic shock, efforts to improve tissue oxygenation (e.g., with blood transfusions) are not justified.

B. Early Management

The management of septic shock described here is based on the most recent guidelines from the Surviving Sepsis Campaign (11). The early management (in the first 6 hours after diagnosis) is outlined in Table 9.3.

Volume Resuscitation

Volume infusion is the first priority in septic shock because cardiac filling is expected to be reduced as a result of: (a) venodilation, and (b) a decrease in intravascular volume from fluid extravasation through “leaky capillaries”.