Page 646 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 52: Acute Lung Injury and the Acute Respiratory Distress Syndrome 465

If one uses a conservative fluid-management strategy aiming to
TABLE 52-13 Salvage Interventions for Patients With Severe Hypoxemia in
Acute Respiratory Distress Syndrome (ARDS) improve lung function and decrease the duration of mechanical ventila-
tion, the clinician’s attention should be focused on the parameters of
Tracheal gas insufflation (TGI) organ function that should be followed in all critically ill patients (eg,
Pressure-controlled inverted ratio ventilation (PC-IRV) mental status, urine output and concentration, circulatory adequacy,
Extracorporeal membrane oxygenation (ECMO) and metabolic evidence of anaerobic metabolism) to ensure that
intravascular pressure is reduced safely. The aim of such an approach
High-frequency oscillatory ventilation (HFOV)
is to find the lowest intravascular pressure compatible with adequate
Inhaled nitric oxide (NO) or inhaled prostacyclin (epoprostenol) functioning of the circulatory system, recognizing that FACTT subjects
Corticosteroids enrolled in the conservative-strategy arm were titrated on average to
a CVP between 8 and 9 mm Hg. Furosemide is often used to achieve
diuresis and net negative fluid balance. Preload can be reduced in part
by meticulous attention to limit all extraneous fluid administration.
(so-called “supercharging”) to peripheral tissues is a necessary strategy Importantly, it is often difficult to identify end inspiration in many
in critically ill patients such as those with sepsis and ARDS, and advo- patients with ALI or ARDS to measure intravascular pressure. This is
cate approaches such as volume loading to achieve this goal. 280,281 This especially problematic if patients are spontaneously breathing while
latter position has fallen out of favor because the oxygen extraction receiving assisted ventilation. To improve accuracy in making routine
defect purported to exist in patients with sepsis and ARDS now seems measurements of intravascular pressures, it is recommended that the
to have been artifactual, or at least not clinically relevant. 282,283 Moreover, airway pressure be transduced and its transducer’s output be printed
controlled clinical trials of such goal-oriented hemodynamic therapy simultaneously with the pressure tracing. The transduced airway pressure
showed no improvement in survival or worse survival. In patients tracing clearly identifies the start of inspiration by the start of its positive
285
284
with ALI and ARDS, the consequence of an approach of maximizing deflection in patients who are not assisting the ventilator. Likewise the
oxygen delivery could be escalating requirements for mechanical ven- airway pressure tracing also easily identifies the start of an assisted breath
tilation, oxygen, and PEEP. To the extent that intensity and duration of by the occurrence of the associated negative pressure deflection. This
supportive therapy are major determinants of complications and organ simple change can significantly decrease interobserver variability. 292
dysfunctions, the net result could be detrimental. Neuromuscular Blockade The use of neuromuscular blockade in patients with
Several retrospective or noninterventional studies have reported data ALI and ARDS is common and controversial. In the ARDSNet ALVEOLI
showing a correlation between survival and net diuresis or reduction in trial, 25% of patients were receiving neuromuscular blocking agents
Ppw. 286-288 Prospective data collection has also demonstrated that titration (NMBA) at enrollment, and the prevalence of use may be even higher.
293
294
of therapy to minimize extravascular lung water in patients with ARDS NMBA are usually administered for a short period of time (1-2 days),
results in decreased ventilator and ICU days. A small clinical trial although use beyond 72 hours is not uncommon. 293,294 The use of NMBA
289
designed to restore the oncotic pressure gradient and reduce the hydro- remains controversial due to the perceived risk that their use is associated
static pressure gradient through the coadministration of albumin and with neuromuscular weakness. 295-297 Due to confounding by inclusion of
diuresis achieved a negative fluid balance and improved oxygenation. 290 patients with sepsis and coadministration of corticosteroids, which have
NHLBI ARDS Clinical Trials Network Comparison of Two Fluid-Management Strategies To been identified as independent risk factors for neuromuscular weakness,
test the optimal fluid-management strategy in patients with ALI, the and inconsistent results, it remains unclear whether NMBA are a risk

ARDSNet investigators conducted the Fluid and Catheter Treatment factor for neuromuscular weakness. 295-297 Based on a small trial that found
Trial (FACTT). FACTT randomized 1000 patients to one of two fluid- that NMBA use for 48 hours in ARDS was associated with improved
291
298
management strategies over 7 days. In a two-by-two factorial design, oxygenation and a trend toward improved mortality, Papazian and
subjects were simultaneously randomized to a strategy guided by the colleagues conducted a multicenter randomized controlled trial of cisa-
299
use of a PAC or CVC. The fluid-management study assessed the risks tracurium use for 48 hours in severe ARDS. The early use of NMBA
and benefits of a conservative fluid-management strategy, titrated to was found to be associated with more ventilator-free days and improved
intravascular pressure goal through the use of diuretics, compared to a 90-day survival after adjustment for covariates, without an increase
299
liberal fluid-management strategy. in neuromuscular weakness as measured by physical examination.
The study protocol aimed for a central venous pressure (CVP) of less However, the mechanism through which these benefits were achieved
than 4 mm Hg in the conservative-strategy group and a CVP of 10 to remains largely speculative. Several hypotheses for the observed benefit
14 mm Hg in the liberal-strategy group. The conservative-strategy arm of NMBA use include that NMBA use may improve respiratory mechan-
experienced higher oncotic pressures and lower intravascular pressures, ics, may facilitate ventilator synchrony to permit lung-protective ventila-
but to a lesser extent than the protocol specified. The preenrollment CVP tion, may decrease oxygen consumption, and cisatracurium may exert
of the study population was 12 mm Hg and was reduced to a CVP of less beneficial anti-inflammatory effects. Alternatively, because it is conceiv-
than 9 by day 7 in the conservative-strategy arm. By study day 7, the able that the protocolization of a sedative strategy to mimic the paralyzed
liberal-strategy group had a CVP in a similar range to the preenrollment state to permit blinding may have been detrimental to subjects enrolled in
CVP. The liberal-strategy group was on average 7 L of fluid net posi- the placebo arm, it seems reasonable to see the results confirmed before
tive by day 7, compared to net even in the conservative-strategy group. adopting the interventions of the treatment arm in usual clinical practice.
Compared to prior studies, 3,4,287 the cumulative fluid balance observed Permissive Hypercapnia Traditionally physicians have attempted to ventilate
in the liberal-strategy group appeared to reflect standard practice. The patients to a normal arterial P CO 2 (see Fig. 52-6). In patients with severe
conservative fluid-management strategy resulted in improved oxygen- lung disease, however, this arbitrary goal has a mechanical cost: the
ation, shorter duration of mechanical ventilation (three fewer days in probable amplification of lung injury (ie, VILI). Increasing evidence
survivors), and ICU length of stay (two more ICU-free days), without an points to the safety and efficacy of allowing the arterial P CO 2 to rise
increase in nonpulmonary organ dysfunction in the short term. There above 40 mm Hg when used in combination with a ventilatory strategy
was no significant difference by fluid-management strategy in regard to that uses low tidal volumes and low plateau pressures. When patients
60-day mortality. However, a recent study of a small sample of long-term with ALI and ARDS are ventilated with volume- and pressure-limited
survivors from FACTT found a signal that enrollment in the conserva- ventilation as described above, the mean Pa CO 2 may rise modestly (into
tive fluid-management strategy was associated with long-term cognitive the low 40s mm Hg) or higher (into the mid-to-high 50s mm Hg) with
28
impairment. This observation requires confirmation as there was no corresponding falls in arterial pH (see Table 52-7). Occasional patients
clear pathophysiologic mechanism to explain the observation. may have a Pa CO 2 above 100 mm Hg 300,301 (see Table 52-7).

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