A large quantity of experimental works, sometimes with conflicting
conclusions, have been published about the regulation of core temperature and
brain temperature. Bedside clinical studies, however, are not that common.
Measurement of cerebral blood flow in comparison with core body temperature
in traumatic brain injury (TBI) patients, as presented in a recent issue of
Critical Care
by Stretti and colleagues, is therefore worth commendation [1].
Cooling the body to protect the brain and preserve life may sound like
something from science fiction. However, cooling seems to have very real
beneficial effects. Some of our friends in the animal kingdom can withstand
remarkable physiologic insults, at least when they are cold. For example,
Spermophilus tridecemlineatus
(ground squirrels) can tolerate 90% reductions in cerebral perfusion without
any neurologic deficit, provided their temperature is reduced to 10?C during
hibernation [2]. In fact, cooling has been used as a therapy in medicine for
decades [3]. Since its inception, enthusiasm for cooling has waxed and waned
in the domains of cardiopulmonary bypass, cardiac arrest, stroke, and TBI
[4]. Because temperature has the potential to alter cerebral metabolism,
blood flow and intracranial pressure (ICP), therapeutic cooling has been
proffered as a management strategy after TBI. However, clinical trials in TBI
have not been conclusive to date [5],[6], prompting a new large-scale
multicenter European trial [7]. In any case, clinical trials usually differ
from scientific procedures because they provide pragmatic answers for
clinicians (if conclusive) but often not for scientists. The need to
establish a link between clinical utility and scientific rationale forces us
to return to simple questions such as that posed by Stretti and colleagues:
what are the brain hemodynamic effects of temperature changes?
The basic tenants underpinning therapeutic cooling in TBI are related to the
fundamental relationship between temperature and the rate of biochemical
reactions common to all species [8], and the effect of temperature on ICP.
The brain may be particularly sensitive to changes in temperature for two
reasons: the brain is highly metabolically active; and, due to the rigid
cranium, temperature-induced changes in metabolism and cerebral blood volume
can result in changes in ICP. The ICP itself is governed by the volume of the
various compartments in the skull; namely, the vascular, parenchymal, and
cerebrospinal fluid (CSF) compartments. The question then arises as to which
component of ICP temperature affects.
The vascular component is the obvious choice because decreasing temperature
increases vascular tone in the small pial vessels [9], and perhaps even in
the basal arteries [10]. Aside from altering the vascular component of ICP,
it is also possible (and as yet unknown) that the CSF or parenchymal
compartments are altered ? for example, by altering CSF production or
reabsorption, or by affecting the osmotic composition of the parenchymal
interstitium. Separating such components will be difficult to achieve
experimentally and especially clinically.
Stretti and colleagues used transcranial Doppler (TCD) ultrasonography during
alteration in body temperature after TBI in an attempt to further our
understanding of the cerebral hemodynamic consequences of cooling. TCD is a
stethoscope for the brain, and its bedside use in several scenarios should be
more widespread. The advantages of TCD measurements on arrival at
neurocritical care, to make a quick assessment and decide about the first few
hours? management strategy, have been highlighted recently [11]. TCD measures
blood flow velocity, not volumetric flow, and because it has a pulsatile
component can (and should) be analyzed with pulse waveform signal processing
methodology. In addition, combining TCD velocity measures with arterial blood
pressure and cerebral perfusion pressure can provide further insight into
cerebral hemodynamics by describing the autoregulation, vascular compliance,
resistance, time constant, wall tension, critical closing pressure, and other
parameters.
In the current study, the relationships between core body temperature and
cerebral hemodynamics were studied in two groups of TBI patients: those with
a fever who were subsequently cooled (defervescence group); and those who
were hypothermic who were warmed to normothermia (rewarming group) [1]. The
mean flow velocity observed in the rewarming group is nearly twice lower than
that in the defervescence group. This disproportion remains apparent even if
the upper temperature in rewarmed patients was close to the lower temperature
in the defervescence group. This observation may suggest that there is no one
universal temperature?cerebral blood flow relationship, and other
physiological variables obviously play a role. The authors report that with
lower temperature we see lower mean arterial pressure and lower TCD
pulsatility index. This is a novel finding. The pulsatility index is
theoretically proportional to the pulsation of blood pressure and
(nonlinearly) to a product of cerebrovascular resistance and arterial
compartmental compliance multiplied by the heart rate, but inversely
proportional to cerebral perfusion pressure [12]. We still know little about
vascular resistance and compliance when temperature varies, and cerebral
perfusion pressure is reported to stay constant at least in the defervescence
group; therefore, it is possible that the lowering of arterial blood pressure
pulse amplitude is responsible for the reduced pulsatility index with lower
temperature.
In conclusion, Stretti and colleagues touch complex and still poorly
chartered phenomena. Because of the multifactorial interactions between brain
injury, temperature control, cerebral blood flow, and autoregulation, the
answer to all questions is impossible within an observational study design
based on a limited number of cases. Nevertheless, this paper opens a
thought-provoking discussion and, we hope, will stimulate further clinical
research in the area of the thermodynamic brain.
Abbreviations
CSF: Cerebrospinal fluid
ICP: Intracranial pressure
TBI: Traumatic brain injury
TCD: Transcranial Doppler
Competing interests
The authors declare that they have no competing interests.
Sumber:
Critical Care.
18 (Dec. 12, 2014): p693.
