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The results of these studies are awaited. Renewed interest in the use of steroids in
similar patients has shown small but significant benefit particularly in those
patients who have an ablated adrenal response to synacthin [17]. A larger scale
study of this approach is being planned.
The hypothesis that the hypotension of sepsis is due to excess production of
nitric oxide (NO) resulting from activation of inducible NO synthase in the vascular
endothelium led to a large double blind randomized study of NO synthase inhibi-
tion using N(G)-monomethyl-L-arginine (L-NMMA) [18]. Unfortunately the treat-
ment group showed no benefit and indeed had a higher mortality than the patients
receiving placebo. This was despite the fact that preliminary animal and patient
data suggested significant improvement. The result of this study raises important
issues of design and appropriate patient recruitment. Were the dosage of L-NMMA
and the target blood pressure too high, and was enough attention paid to cardiac
output where it was measured?
It might be concluded from the tenor of this chapter thus far that the importance
of blood pressure monitoring and its use as a therapeutic target has been down-
played and this is true to a certain extent. As discussed earlier, routine intra-arterial
monitoring of blood pressure has become standard for a variety of reasons in the
ICU. Until fairly recently this had been done purely for reasons of convenience and
patient comfort. For a long time, however a minority of investigators have shown
that analysis of the arterial pulse wave contour obtained from an intra-arterial line
can provide a great deal of information over and above just the value for arterial
pressure [19\u201321]. This has led to the development of two commercially available
technologies for the continuous monitoring of cardiac output obtained by analyz-
ing the pulse wave contour obtained from intra-arterial catheters placed in either
the radial or femoral arteries.
Each of these technologies uses rather different protocols for measuring the area
under the pressure wave form but both calibrate the area using transpulmonary
thermodilution in the case of PiCCO, and lithium dye dilution in the case of LiDCO.
These technologies have clearly added a new dimension to arterial pressure moni-
toring and provide beat-by-beat information on stroke volume and cardiac output
94 D. Bennett
Intriguingly, these technologies are being used to determine whether critically
ill ventilated patients will respond to volume loading based on a considerable
literature [26\u201328]. A greater than 10 or 12% variability of systolic pressure and/or
pulse pressure caused by the positive pressure associated with peak inspiration
indicates that the patient is probably hypovolemic and is likely to respond to fluid
resuscitation. This is an important technological development because occult
hypovolemia is probably not uncommon in critically ill patients and if unrecog-
nized is likely to contribute to an increase in both morbidity and mortality.
Thus, if systolic or pulse pressure variability increases and exceeds 10 to 12% it
implies developing hypovolemia and should allow much earlier recognition and
treatment with volume replacement being administered more precisely to the point
where variability is less than 10%. This approach can only be used in ventilated
patients although there are probably a significant number of non-ventilated ICU
patients who are relatively hypovolemic, which again is unrecognized.
As a future development, it would be interesting to study such patients using the
response of the intra-arterial pressure trace to the Valsalva maneuver as an indi-
cator of fluid status. There is, of course, an extensive literature [29\u201332] describing
various applications of the maneuver but the square wave response in patients with
left ventricular failure is probably the best known.
Figure 1a demonstrates the sinusoidal response of a group of normal subjects
with the early rise in blood pressure as intra-thoracic pressure rises, followed by
the tachycardia and subsequent sharp fall due to a reduction in stroke volume
related to the decline in myocardial transmural pressure and ventricular volumes.
Following release of breath holding, the over shoot in stroke volume is reflected by
the increase in systolic pressure and bradycardia.
In contrast, Figure 1b shows the response to the maneuver in the same subjects
who had been made hypervolemic by ingestion of a volume of 0.9% saline equiva-
lent to 2% of their lean body mass. The difference is very obvious with a typical
square response, classical of volume overload. Hypovolemia was then produced by
administering 30 mg of furosemide. The study also showed that the maximal fall
in systolic pressure was greatest in the hypovolemic subjects and least in the volume
loaded subjects [32].
Blood pressure is one of the most frequently measured variables in medicine and
is obviously of great importance in detecting patients with clinical hypertension
and monitoring their subsequent treatment. However, in critically ill unstable
patients its use may have been overemphasized. The reliance on systolic pressure
in trauma patients may well be cloaking important hypovolemia that can only be
detected by direct measurement of flow or surrogates such as central or mixed
venous saturation, base deficit, and lactate.
Similarly the reliance on mean pressure in septic patients may be misleading,
particularly when it is high and the optimal level at which to maintain pressure in
such patients is still unclear. Furthermore, there is still uncertainty about which
agent to use to achieve the desired pressure. The notion that so much reliance is
Arterial Pressure: A Personal View 95
placed on pressure is related to the fact that it has for a very long time been relatively
easy to measure and it is only rather more recently that flow measurements have
become routine in most ICUs.
It is gratifying, therefore, that with the advent of pulse contour analysis, pressure
and flow data can be obtained from a single signal from which the state of volemia
can be estimated. It is not the intention of the author to discourage clinicians from
measuring blood pressure but to encourage better understanding of the relation-
ship between pressure and flow. The emergence of the new technologies may go a
long way to achieving this end.
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