Page 849 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

580 PART 5: Infectious Disorders

GENERAL TREATMENT STRATEGIES lung dependent both increases perfusion based on gravity as well as
limiting overinflation of the good lung and is very effective in this
Understanding the pathophysiology of pneumonia can lead to rational situation. If hypoxemia is refractory, ibuprofen appears to block the
treatment strategies. While many principles apply to severe infections bacterial-induced paralysis of hypoxic vasoconstriction and has been
in general, several aspects are unique to the treatment of pneumonia. demonstrated to be safe in critically ill patients. 27
■ ANTIBIOTIC TREATMENT ■ SEPTIC SHOCK

Obviously, appropriate antibiotic therapy is key to adequate control of Patients with CAP appeared to respond to drotrecogin alfa activated
pneumonia. The time to initial antibiotic dose appears to be an impor- and tifacogin much better than patients with HAP or nonpneumonia
tant determinant of outcome if the patient is in septic shock. The infections, 28,29 consistent with the important role that the coagulation
20
benefit of rapid initiation of antibiotics in other clinical presentations is system plays in CAP. However, a negative prospective randomized trial
less clear, particularly if the patient has inadequate volume resuscitation. of tifacogin in severe CAP (SCAP) and of drotrecogin alfa activated
19
The Jarisch-Herxheimer reaction sometimes seen with the use of cell in all-cause septic shock did not confirm these subgroup analyses and
wall active antibiotics and highly susceptible bacteria may actually lead neither drug is now available clinically.
to hypotension if antibiotics are given prior to adequate fluid resuscita-
tion. Appropriate empirical antibiotic therapy will be discussed below COMMUNITY-ACQUIRED PNEUMONIA
for each of the separate clinical pneumonia syndromes.
If release of exotoxins appears to be playing an important role, such Community-acquired pneumonia continues to be a frequent cause of
as with S aureus and some streptococcal pneumonias, use of antibiotics morbidity and mortality. Worldwide CAP is the leading infectious dis-
that interfere with ribosomal protein synthesis may be of some benefit. ease cause of death and the third leading cause of death overall. Despite
1
This appears to be particularly important for community-acquired continued advances in a multitude of areas in medicine, the mortality
methicillin-resistant S aureus (CA-MRSA). The concern in this rate from CAP has changed very little in the past four decades. In addi-
21
infection is that neither vancomycin nor linezolid is rapidly bacteri- tion to the deaths within the hospital, patients admitted to the hospital
cidal, allowing viable bacteria to continue to release exotoxin. However, with pneumonia are at an increased risk of death for months to years
linezolid suppresses exotoxin production in viable bacteria, as does after discharge, relative to age-matched controls. 30-32
to vancomycin may have benefit in pneumonia due to toxin-secreting ■ EPIDEMIOLOGY
clindamycin. Therefore, use of linezolid or the addition of clindamycin
strains. For MSSA, and streptococcal infections in general, the rapid kill- For the year 2000, over 1 million patients were hospitalized in the United
ing with β-lactam antibiotics effectively eliminates exotoxin production. States, and 65,000 deaths were attributable to CAP and influenza. The
33
The presence of cavities may decrease antibiotic penetration to the financial cost is substantial as well, estimated at over $9 billion per year. 34
site of infection. This does not appear to be a problem with anaerobic Approximately 10% of all patients hospitalized with CAP require
pleuropneumonia, possibly because vascular invasion is not as promi- ICU admission. 35-38 Hospitalized CAP patients carry significant mortal-
nent a feature as it is with Pseudomonas and CA-MRSA pneumonias. ity depending on the severity of illness. Several studies have reported a
Aerosolized antibiotics may therefore be required, although this is much mortality rate of approximately 10% in hospitalized ward patients, and
less likely than in treatment of VAP. 30% to 60% mortality in patients that require ICU admission. 19,39 SCAP
■ VENTILATORY SUPPORT is even more burdensome to health care systems as the mean duration
of hospitalization is 6 days at a cost of approximately $7500 for ward
Several aspects of the pathophysiology of severe pneumonia provide patients compared to 23 days and $21,144 for ICU patients. 40
unique challenges to ventilatory support. The most important determinant of hospitalization and mortality
in patients with CAP is the presence of chronic comorbid conditions. 38,39,41-44
Noninvasive Ventilation: Concern about noninvasive ventilation (NIV) The most common comorbid illnesses in patients with SCAP are
in patients with pneumonia was raised early in its development. chronic obstructive pulmonary disease (COPD), 38,45,46 which is pres-
Patients clearly cannot adequately expectorate against continuous ent in up to half, followed by alcoholism, chronic heart disease, and
positive airway pressure (CPAP) delivered via a full-face mask. A diabetes mellitus. 38,44,47
very productive cough with pneumonia remains one of the relative
contraindications to NIV. Failure of NIV in these patients has been ■ ETIOLOGIC SPECTRUM
22
associated with a subsequent prolonged duration of mechanical ven- While all CAP studies identify S pneumoniae as the leading pathogen
tilation and increased risk of VAP. However, intermittent NIV with causing CAP, the frequency of other pathogens varies regionally or
23
careful attention to increasing secretion clearance prior to restarting with outbreaks of particular pathogens (Table 65-3). More importantly,
NIV and possibly use of a nasal-only mask appear to minimize this significant differences between the etiology of milder pneumonia and
risk. NIV has been demonstrated to have a survival benefit in CAP severe disease exist. For example, Legionella pneumophila appears to be
24
and immunocompromised patients with pulmonary infiltrates. 25
more common in SCAP, at least in some areas, while other atypical
48
Severe Hypoxemia on Mechanical Ventilation: Occasionally, patients pathogens like Mycoplasma pneumoniae and Chlamydophila pneumoniae
with unilateral pneumonia developed worsening hypoxemia after are much less common. Gram-negative pathogens such as Escherichia coli
intubation and initiation of mechanical ventilation. Positive end- and Klebsiella pneumoniae, again with significant regional differences, are
expiratory pressure (PEEP) may actually exacerbate the problem. also more common in severe disease. While uncommon in most series,
49
The pathophysiologic mechanism is overdistention of the alveoli in P aeruginosa may also be an important SCAP pathogen in some centers.
the unaffected lung with the resultant increase in pulmonary capil- Whether this is due to innate virulence of the pathogen or a reflection of
lary pressure shunting more blood from the unaffected lung to the the comorbidities in patients who acquire them is uncertain.
pneumonic lung. Knowledge of the local etiology is particularly important in the set-
Several strategies may be effective in this situation. Clearly, these ting of SCAP and shock as this will significantly impact on both empiric
patients should be treated with a lower tidal volume, such as the 6 mL/kg therapy and the microbiological investigations ordered. Examples of
ideal body weight used for ALI, to minimize overdistension of the pathogens that can cause severe pneumonia and septic shock that are
26
unaffected lung. However, PEEP should be adjusted to maximize oxy- significant considerations in some areas and nonexistent in others
genation rather than by use of the ARDSNet algorithm. Positioning are Burkholderia pseudomallei, Acinetobacter spp, L longbeachae, and
the patient in the lateral decubitus position with the unaffected Francisella tularensis.

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