Biomedical Engineering Reference
In-Depth Information
mation alone (22). Godin and colleagues demonstrated precisely such loss of
variability in humans experimentally exposed to bacterial endotoxin, a common
predecessor of MODS (23). Seiver and Szaflarski (24) reported a startling loss
of physiologic variability with the appearance of monotonous sinusoidal varia-
tion in cardiac output among critically ill humans. Winchell and Hoyt have
shown that loss of heart rate variability in critically ill patients is a predictor of
death (25).
5.
IMPLICATIONS FOR TREATMENT
If MODS is the clinical expression of network recoupling failure, then ther-
apy might logically be directed toward facilitating that recoupling. Paradoxi-
cally, severe illness prompts physicians to suppress biologic variation in many
organ systems. For example, ventilators are set to fire at fixed intervals, cate-
cholamines are infused at fixed rates, fixed composition nutrition is adminis-
tered without interruption, venovenous hemofiltration is conducted at a fixed
rate around the clock, and so on. Such rigidity invites perceptions of therapeutic
success: "the patient in bed 21 is now stable as a rock." Perhaps the more impor-
tant question is whether such therapeutic rigidity promotes or suppresses clinical
recovery.
Although no trials have been performed on patients with MODS, reports
have begun to appear in which normal physiologic variability has been syntheti-
cally applied to the function of mechanical ventilators. Gas exchange and respi-
ratory mechanics are improved by biologically variable ventilation not only
in models of lung injury but also in healthy lungs (26,27). More to the
point, a group of patients at risk for MODS—those undergoing surgical repair of
abdominal aortic aneurysm—also enjoyed better lung function when the ventila-
tion algorithm included simulated biological variation (28). Part of the im-
provement may reflect enhancement of the respiratory sinus arrhythmia (30).
During cardiac surgery, the perfusion of the body is supported by the
"heart-lung" machine. This perfusion, called cardiopulmonary bypass, can be
continuous, pulsatile at fixed sinusoidal frequency, or aperiodically pulsatile.
Mutch and colleagues have demonstrated improved brain blood flow character-
istics with the aperiodic (biologically variable) algorithm versus the conven-
tional clinical techniques of constant or periodic flow (29). Suboptimal brain
blood flow is clinically associated with cognitive impairment, a manifestation of
central nervous system "organ failure."
While none of these data directly address MODS, they raise the disquieting
possibility that conventional therapeutic rigidity that applies fixed or strictly
periodic inputs to the network of dysfunctional biological systems may actually
hinder recovery. The need for trials comparing monotonous versus biologically
variable algorithms applied to existing therapies is evident.
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