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374
T. Kalb
Fig. 1. Cumulative effective antimicrobial initiation following the onset of septic-shockassociated hypotension and associated survival. The x-axis represents time (hr) following
the first documentation of septic-shock-associated hypotension. The black bars represent
the fraction of patients surviving to hospital discharge for effective therapy initiated
within the given time interval. The gray bray represent the cumulative fraction of patients
having received effective antimicrobials at any given time point.
With permission from Kumar et al. (2006) Crit Care Med 34: 1589–1596.
Role of Monitoring: What to Measure — When and How Reliable
Measurement of preload (LVEDV) by echocardiography is a relative
measure of cardiac filling, though this is poorly predictive of volume
responsiveness. Likewise, a static indirect measure of preload by CVP has
poor discriminative capacity to identify patients who will respond to additional fluid administration with augmented stroke volume.
12
Respiratory
cycle thoracic pressure variations influence volume and pressure estimates of preload, so that the greater the preload deficit, the greater the respiratory cycle variation. Several novel monitoring strategies have been
offered that take advantage of dynamic respiratory cycle variation, and
may provide a useful predictive index of preload deficit that is a better
clinical determinant than CVP. Among dynamic indications of cardiac filling, the IVC collapsibility index has been shown to perform better than
CVP in detecting preload deficit and predicting response to fluid bolus
administration.
13
Continuous measurement of ScvO2, as a monitoring target of EGDT
as described by Rivers et al. has not been widely adopted and requires
specialized invasive monitoring. Moreover, among patients with septic
shock who were treated to normalize central venous and mean arterial
pressure, additional management to normalize lactate clearance, targeting
at least 10% decreased lactate as a goal of an initial 6 hr of resuscitation,
compared with management to normalize ScvO
2
, did not result in signifi-
cantly different in-hospital mortality.
14
Other Therapeutic Considerations/Controversies
Transfusion of PRBCs is a controversial part of a bundled goal directed
therapy that has not been independently validated. Although transfusion may
increase oxygen content, it has limited or negative oxygen consumption benefit in the setting of microcirculatory disturbance in sepsis and critical illness.
Restrictive transfusion policy targeting Hgb >7.0 is recommended in
sepsis and other critical illnesses that render patients at risk for ARDS and
MODS, with associated augmented mortality risk.
15
Guidelines such as the Surviving Sepsis Campaign currently maintain
that hydrocortisone < 300 mg/day should be administered for volume non-
responsive septic shock (Table 3). Nevertheless, no mortality benefit has
been reproducibly demonstrated, perhaps owing to the inclusion of large
numbers of patients who received etomidate which blocks steroid metabolism in the single trial that purported to show such a benefit. Cortrosyn
stimulation testing is no longer recommended, based on the recognition
that nonresponder information is obtained in retrospect and does not
clearly predict a pressor-sparing effect.
16
Initial enthusiasm for intensive insulin therapy to improve outcome in
sepsis and septic shock has been tempered by poor reproducibility of benefit in multiple trials, largely attributed to the counterbalancing effect of
excess hypoglycemia and an associated increased risk of death.
17
A prudent recommendation is to maintain BG <150 with careful attention to
hypoglycemia by insuring adequate nutrition through the enteral or intravenous route.
375
Manifestations and Management of the Host/Pathogen/Physician Response
For those patients who manifest oliguric renal failure, CVVH offers
no benefit compared to intermittent hemodialysis in the absence of
demonstrated hemodynamic intolerance to a trial of dialysis.
18
The action of rAPC to improve outcome in severe sepsis is controversial, based on poor reproducibility of initial demonstration of benefit
in a carefully selected cohort. Actions of APC in sepsis are thought to
relate to anti-inflammatory properties as well as improvement in blood
fluidity which may affect microcirculation. rAPC is considered possibly
indicated in a carefully selected group of patients with a narrow timeline
for initiation within the first 24 hr in patients with a compact clinical
presentation, limited bleeding risk, and a high mortality estimate based
on Apache II > 25.
19
Agents with vasodilatory properties have been purported to improve
microcirculatory flow in sepsis, though the added clinical benefit of these
interventions remains unclear. Such agents as dobutamine, cholinergic
agonists, and therapy, which increase nitric oxide bioavailability (e.g. IV
nitroglycerine), are undergoing investigation for this activity, though it
has not-yet-demonstrated clinical value.
Targeted therapy aimed at interruption of individual inflammatory cascade elements (e.g. anti-TNF mAb) has been largely disappointing, with no
mortality benefit in a wide variety of trials. Patients with severe sepsis
invariably present after the initial innate response, which is short-lived and
results in myriad downstream cascades including counterregulatory and
potentially compensatory anti-inflammatory responses (CARS). The systems-based approach to cell signaling in sepsis has provided insight into
the vast array of interwoven and time-sensitive signaling nodes and crosstalk which expose the complex task of clinically meaningful amelioration
of sepsis by any strategy that targets early mediators of sepsis.
20
Outcome Analysis and Prognosis
The prognostic assessment in sepsis is linked to the detection of multiorgan failure and is influenced by host factors related to comorbid illness
and chronic illness. Genomic and epidemiologic characteristics contribute
376
T. Kalb
377
Manifestations and Management of the Host/Pathogen/Physician Response
p
Table 5. Sequential Organ Failure Assessment (SOFA) Score Schematic
SOFA Score 0 1 2 3 4
With Respiratory Support
Respiration, >400 ≤ 400 ≤ 300 ≤200 ≤100
Pao
2
/FIo2 mm Hg
Coagulation, > 150 ≤150 ≤100 ≤50 ≤ 20
platelets ×
10
3
/Vmm
3
Liver, bdlinibin, < 1.2 (<20) 1.2–1.9 (20–32) 2.0–5.9 (33–101) 6.0–11.9 (102–204) > 12.0 (> 204)
mg/dL (µmol/L)
Cardiovascular, No hypotensdon MAP Dopamine ≤ 5 or Dopamine >5 or Dopamine >l5 or
hypotension < 70 mm Hg dobutamine epinephrine ≤0.10 epinephrire >0.1 or
(any dose)
a
norepinephrine ≤0.1
a
no repinephrine
> 0.1
a
Central nervous 15 13–14 10–12 6–9 < 6
system,
Glasgow Coma
Scale score
Renal, creatinine, <1.2 (<110) 1.2–1.9 2.0–3.4 3.5–1.9 >5.0 (> 440)
mg/dL. (µmol/L) (110–170) (171–299) (300–440)
Or urine output or < 500 mL/day or < 200 mL/day
MAP, mein arterial pressure.
a
Adrenergic agents administered for ≥ 1 hr (doses given are in µg/kg/min).
With permission from: Dubois et al. (2006) Crit Care Med 34(10): 2536–2540.
378
T. Kalb
to host factor susceptibility to MODS and increased mortality in sepsis.
For example, polymorphisms in TNF-alpha, a history of alcoholism, and
African-American heritage have all been associated with worse outcome.
The action of rAPC in severe sepsis is controversial, based on poor reproducibility of initial demonstration of benefit in selected cohorts of septic
patients. Actions of APC in sepsis are thought to relate to anti-inflammatory
properties as well as blood fluidity properties that may affect microcirculatory
disturbances in sepsis.
19
Until recently, rAPC was available as drotrecogin
alpha [Xigris] for administration for carefully selected patients with severe
sepsis with APACHE II >25. However, in a recently completed clinical trial,
the PROWESS-SHOCK trial, drotecogin alpha [Xigris] failed to show a survival benefit. Results based on preliminary analyses done by Eli Lilly and
Company, that were submitted to the FDA, showed a 28-day all cause
mortality rate of 26.4% in Xirgis-treated patients as compared with 24.2% in
placebo-treated patients, equivalent to a relative risk of 1.09; with a p-value
of 0.31, which is not statistically significant. As a result, the FDA announced
in October 2011 that Ely Lilly has voluntarily withdrawn drotrecogin alpha
from the market and is no longer available for patient adminstration.
Generating an APACHE II score had been utilized to assess the risk/benefit of
rAPC administration, and may similarly be used to stratify patients for future
novel therapeutics. Severity scoring systems have limited predictive power
for individual patients at presentation, are limited to an ICU cohort, and may
be logistically cumbersome to generate. Web-based severity score assistance
is available from many sources (see www.medal.org). Simpler consolidated
scoring modalities have been offered to improve routine incorporation into
clinical activities.
Lastly, scoring schemes that also document the trajectory of response
over time to therapy or accumulated organ dysfunction offer a better discriminator of outcome than initial admission screening modalities alone.
The SOFA (Sequential Organ Failure Assessment) is presented in Table 5,
and is more streamlined, with fewer physiologic variables than APACHE.
SOFA assessment may inform decision making and adjust goals of care in
patients who demonstrate progressive organ failure assessment despite
resuscitative efforts.
21
References
1. Levy MM, Fink MP, Marshall JC, et al. (2003) 2001 SCCM/ESICM/
ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive
Care Med 29: 530–538.
2. Kawai T, Akira S. (2007) TLR signaling. Sem Immunol 19: 24–32.
3. Esmon CT. (2006) Inflammation and the activated protein C anticoagulant pathway. Sem Thomb Hemost 32(Suppl 1): 49–60.
4. Jansen JRC, Maas JJ, Pinsky MR. (2010) Bedside assessment of mean
systemic filling pressure. Curr Opin Crit Care 16: 231–236.
5. Hunter JD, Doddi M. (2010) Sepsis and the heart. Br J Anaesth
104(1): 3–11.
6. Landry DW, Oliver JA. (2001) The pathogenesis of vasodilatory
shock. New Engl J Med 34(8): 588–593.
7. Sakr Y, Dubois MJ, De BD, et al. (2004) Persistent microcirculatory
alterations are associated with organ failure and death in patients with
septic shock. Crit Care Med 32: 1825–1831.
8. Jones AE, Brown MD, Trzeciak S, et al. (2008) The effect of a quan-
titative resuscitation strategy on mortality inpatients with sepsis: A
meta-analysis. Crit Care Med 36: 2734–2739.
9. Levy MM, Dellinger RP, Townsend SR, et al. (2010) The surviving
sepsis campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med
38: 367–374.
10. Gaieski DF, Mikkelsen ME, Band RA, et al. (2010) Impact of time to
antibiotics on survival in patients with severe sepsis or septic shock in
whom early goal-directed therapy was initiated in the emergency
department. Crit Care Med 38: 1045–1053.
11. Beale SJ, Hollenberg SM, Vincent JL, Parillo JE. (2004) Vasopressor
and inotropic support in septic shock: An evidence-based review. Crit
Care Med 32(Suppl): S455–465.
12. Marik PE, Baram M, Vahid B. (2008) Does central venous pressure
predict fluid responsiveness? A systematic review of the literature and
the tale of seven mares. Chest 134: 172–178.
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Manifestations and Management of the Host/Pathogen/Physician Response
13. Nagved AD, Merchant RC, Tirado-Gonzalez A, et al. (2010) Emergency
department bedside ultrasonographic measurement of the caval index
for noninvasive determination of low central venous pressure. Ann
Emerg Med 55: 290–295.
14. Jones AE, Shapiro NI, Trzeciak S, et al. (2010) Lactate clearance vs
central venous oxygen saturation as goals of early sepsis therapy: A
randomized clinical trial. JAMA 303(8): 739–746.
15. Marik PE, Corwin HL. (2008) Efficacy of red blood cell transfusion
in the critically ill: A systematic review of the literature. Crit Care
Med 36: 2667–2674.
16. Marik PE. (2009) Critical illness–related corticosteroid insufficiency.
Chest 135: 181–193.
17. Marik PE, Preiser J-C. (2009) Toward understanding tight glycemic
control in the ICU. A systematic review and metaanalysis. Chest 137:
544–551.
18. Cariou A, Vinsonneau C, Dhainaut J-F. (2004) Adjunctive therapies
in sepsis: An evidence-based review. Crit Care Med 32(Suppl):
S562–S570.
19. Barie PS. (2008) Current role of activated protein C therapy for severe
sepsis and septic shock. Curr Infect Dis Rep 10: 368–376.
20. Gilchrist M, Thorsson V, Li B, et al. (2006) Systems biology approaches
identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 441:
173–178.
21. Minne L, Abu-Hanna A, de Jonge E. (2008) Evaluation of SOFAbased models for predicting mortality in the ICU: A systematic
review. Critical Care 12(6): R161.
380
T. Kalb
Management of the Mechanically
Ventilated Patient
Uma S. Ayyala
Key Pearls
• Modes of mechanical ventilation differ in how a breath is delivered,
sustained, and terminated, as well as the degree of ventilatory support
provided to a patient. Patients with specific clinical conditions may
benefit from one mode over another.
• Patients who are mechanically ventilated require continuous hemodynamic as well as laboratory data to provide information about gas
exchange.
• Supportive care of the mechanically ventilated patient includes adequate sedation and analgesia that can relieve pain and help prevent
patient–ventilator dyssynchrony.
• Respiratory distress on the mechanical ventilator can be life-threatening
and requires immediate attention. In addition to physical exam, laboratory and imaging data, evaluation of respiratory parameters such
as peak and plateau airway pressures can help identify the root of
distress.
• Liberation from the ventilator requires a patient to be clinically ready
prior to initiating a spontaneous breathing trial. Successful weaning
requires daily interruption of sedatives and a multidisciplinary, protocolized approach.
381
32
Chapter
*Mount Sinai School of Medicine, New York, NY, USA.
Introduction
Respiratory failure requiring mechanical ventilation can be caused by a
variety of medical conditions. Most commonly, mechanical ventilation is
initiated for hypoxemic respiratory failure, hypercapnic respiratory failure,
altered mental status requiring a stable airway, respiratory muscle fatigue,
and bronchospasm. A thorough understanding of the modes and parameters of ventilators, as well as the management of complications from
mechanical ventilation, is important in order to safely provide this therapy
to patients.
Initiation of Mechanical Ventilation
Modes and Settings
Volume, pressure, and flow are three interrelated variables in all forms of
mechanical ventilation. Modes of ventilation are differentiated by how
inspiration is initiated (trigger variable), maintained (limit variable), and
terminated (cycle variable). A breath is triggered by a preset variable —
most often either pressure or flow. Then an inspiration is maintained and
cycles to expiration once a preset measure of volume, pressure, flow, or
time is met.
The three most common modes of mechanical ventilation are assist
control ventilation (ACV), spontaneous intermittent mechanical ventilation (SIMV), and pressure support ventilation (PSV), as outlined in
Table 1. ACV imposes the least amount of work of breathing for a patient
and therefore is the most widely used mode.
1
In this mode, the ventilator
supports every breath. A baseline respiratory rate (RR) is set, though the
patient may breathe over this rate. The ACV mode can be either volumeor pressure-cycled. In volume-cycled ACV, a baseline RR, inspiratory
flow, and tidal volume (TV) are designated with the dependent variable
being airway pressure. Conversely, with pressure-cycled ACV, a peak
inspiratory pressure (PIP), inspiratory time (T
i
), and RR are set with TV
as the dependent variable. This mode provides the advantage of controlling airway pressures but with the drawback of not guaranteeing a specific
382
U.S. Ayyala
TV and therefore minute ventilation. The SIMV and PSV modes provide
less ventilatory support for patients but offer some advantages regarding
patient comfort and use as weaning modalities (Table 1).
Once a mode of ventilation is decided on, other settings, such as RR,
delivered oxygen (F
iO2
), positive end expiratory pressure (PEEP), and
inspiratory flow, can be chosen (Table 2). When volume-cycled ACV is
used, PIP and plateau pressure (P
plat
) can be measured. PIP is the highest
383
Management of the Mechanically Ventilated Patient
Table 1. Modes of Mechanical Ventilation
Ventilator Cycle
Mode Support Variable Description
AC Full Volume or Preset: RR, TV or Pi, PEEP, inspiratory
pressure flow, FiO
2
.
Patent can overbreathe set rate and will receive
set TV.
Adv: For critically ill patients who require full
ventilatory support.
Disadv: May be more uncomfortable than partial
support modes and requires sedation.
SIMV Partial Volume or Preset: RR, TV or Pi, PEEP, inspiratory flow or
pressure inspiratory time, PS for spontaneous breaths,
FiO
2
.
Pt can overbreathe set rate and will receive PS.
Adv: Better patient–ventilator synchrony;
auto-PEEP less likely.
PSV Partial Flow Preset: Pressure support level, PEEP, FiO
2
.
There is no set RR — pt must initiate a breath
which delivers an inspiratory pressure until
the inspiratory flow decreases to a preset
threshold.
Adv: Mode of weaning, more comfortable for pt.
Disadv: Pt needs to be awake to trigger vent,
not suitable for full mechanical ventilatory
support.
T-piece Spontaneous None No ventilator support at all — oxygen level
is the only setting. Pt must breathe through
ETT.
Adv: Ideal mode for weaning.