Heart Failure Clinical Trial
Official title:
Skeletal Muscle Oxygenation in Critically Ill
It is possible to measure skeletal muscle tissue oxygenation (StO2) using near infrared spectroscopy(NIRS). It is performed non invasively. We want to compare usually used invasive methods for assessing adequacy of flow to StO2 in critically ill. Aim is to faster and non invasively estimate adequacy of flow to make therapeutic algorithms efficient.
Introduction
The duration and severity of tissue hypoxia have been related to increased mortality.
Maintenance of adequate oxygen delivery (DO2) is essential to preserve organ function, as a
sustained low DO2 is a path to organ failure and death. DO2 does not have influence on oxygen
consumption (VO2) until it reaches critically low values (DO2crit), when VO2 starts to fall.
Low cardiac output states (cardiogenic, hypovolemic and obstructive types of shock), anemic
and hypoxic hypoxemia are characterized by a decreased DO2 but preserved oxygen extraction
ratio (OER=the ratio of DO2 to VO2, VO2/ DO2) so that DO2crit remains normal. In distributive
shock, the oxygen extraction capability is altered so that the critical oxygen extraction
ratio is typically decreased. These situations are typically associated with an increased
DO2crit, and VO2 can become dependant on DO2 even when the latter is normal or elevated.
These observations help to characterize the four principal types of circulatory shock,
however this classification is somewhat simplistic as several types of alternations may
coexist, in particular in cardiogenic shock. Rhodes et al. reported that outcome was more
favorable in septic patients whose VO2 increased after dobutamine administration. DO2 also
increased in survivors. On the other hand DO2 did not increase in patients whose VO2 did not
increase. In dobutamine test proposed by Rhodes et al. the hemodynamic response was
influenced by cardiovascular reserve and the degree of stimulation of adrenoreceptors at
baseline. Unfortunately global measurements of DO2 and VO2 may not be sensitive enough to be
clinically relevant. They may fail to detect regional perfusion abnormalities as in
splanchnic circulation.
Measurement of mixed venous oxygen saturation (SvO2) from the pulmonary artery is used for
the calculations of the VO2 and has been advocated as an indirect index of tissue of tissue
oxygenation and prognostic predictor in critically ill patients. Catheterization of pulmonary
artery is costly, has inherent risks and its usefulness remains under debate. Not
surprisingly the monitoring of central venous oxygen saturation (ScvO2) was suggested as a
simpler and chipper assessment of global DO2 to VO2 ratio.
Near infrared spectroscopy (NIRS) is a technique for continuous, non-invasive, bedside
monitoring of tissue oxygen saturation (StO2). Like pulse oximetry, NIRS uses the principles
of light transmission and absorption to non-invasively measure the concentrations of
oxygenated hemoglobin and reduced hemoglobin in tissue. NIRS offers greater tissue
penetration and does not discriminate between compartments. Therefore it provides a global
assessment of oxygenation in all vascular compartments (arterial, venous and capillary) in
sample volume of underlining tissue. We have previously shown that thenar muscle tissue
oxygen saturation during stagnant ischemia decreases slower in septic shock patients compared
to patients with severe sepsis, localized infection and healthy volunteers. This may be due
to microcirculatory or metabolic changes, and probably correlates to muscle tissue oxygen
consumption. The rate of StO2 decrease correlated with SOFA score, norepinephrine
requirement, and plasma lactate concentration. As recently described, StO2 in sample volume
of underlining tissue depends in vivo on 3 major determinants: the concentration in
oxy-hemoglobin, capillary recruitment and the vascular size (vasodilatation or constriction).
The StO2 during stagnant ischemia has then to be viewed in light of these determinants. The
gradual decrease (slope) of StO2 after cuff inflation-induced vascular occlusion depends
mainly on the augmentation of the concentration of deoxy-hemoglobin and estimates tissue
oxygen consumption and to a lesser degree on vessel de-recruitment. The StO2 upslope during
reperfusion (cuff deflation) can be analyzed in light of flow papers during
ischemia/reperfusion test. Vasodilatation after ischemia leads to recruitment of more vessels
and increase in the local blood flow, which in turn results in a StO2 increase. It remains
unclear which of the described changes is more influential, however this StO2 increase
mirrors the maximal local DO2 at the time of measurement. The development on NIRS signal
processing might be able to provide a clinical important tissue hemoglobin concentration
index and local oxygen consumption as shown by De Blasi et al., such an index may help to
clarify the mechanism(s) by which StO2 signal varies.
The aim of our study was to study skeletal muscle oxygen kinetics in low flow state due to
combined cardiogenic and septic circulatory failure, relate it with central heamodynamic
variables and outcome. We hypothesized that basal StO2 could relate to ScvO2, because blood
flowing through upper limb muscles importantly contributes to flow through superior vena
cava. The second hypothesis was that decrease of skeletal muscle OER and lower muscle oxygen
consumption are more pronounced in patients with septic component of circulatory failure due
to microcirculatory and metabolic changes seen in sepsis, what results in higher mortality.
MATERIALS AND METHODS
Patients Study protocol was approved by the National Ethics Committee of Slovenia, informed
consent was obtained from all patients or their relatives. Study was performed during October
2004 and January 2006. After initial hemodynamic resuscitation, transthoracic ultrasound
heart examination was performed in all patients admitted to our ICU. In patients with primary
heart disease, low cardiac output, and no signs of hypovolemia, a right heart catheterization
with a pulmonary artery floating catheter (PAFC)(Swan-Ganz CCOmboV CCO/SvO2/CEDV, Edwars Life
Sciences, USA) was performed after decision of treating physician. The site of insertion was
confirmed by the transducer waveform, the length of catheter insertion and chest radiography.
In all patients systemic arterial pressure was measured invasively using radial or femoral
arterial catheterization. Patients with inserted PAFC and signs of low flow state (cardiac
index less then 3.0 L/min/m2) were included in our study. PAFC data were calculating using
standard formula.
Localized infection, severe sepsis and septic shock were defined according to ACCP/SCCM
consensus conference definitions (1992). All patients received standard treatment of
localized infection, severe sepsis and septic shock including: source control, fluid
infusion, catecholamine infusion, organ failure replacement and/or support therapy, intensive
control of blood glucose and corticosteroid substitution therapy. Mechanically ventilated
patients were sedated with midazolam and/or propofol infusion and no paralytic agents were
used.
Measurements
Skeletal Muscle Oxygen Kinetics
Thenar muscle StO2 was measured non-invasively by NIRS (15mm Probe, InSpectra™, Hutchinson
Technology Inc., USA). The values were continuously monitored and stored into a computer
using InSpectra ™ software. The StO2 was monitored before, during and after upper arm
ischemia-reperfusion test (UIRT) which was standardized as follows: a rapid cuff inflation
above elbow towards 260 mmHg to stop flow and to induce a decrease in StO2 for 90 seconds,
cuff deflation with continuous measurement of StO2 increase, overshooting and stabilization.
Measurements were performed immediately after PAFC insertion (in first 24 to 72 hours after
admission), the second measurement was performed 12-24 hours after the first measurement, the
third measurement was performed (only if patient was still alive and still had PAFC inserted)
in 48 hours after the first measurement. In spontaneously breathing patients and healthy
volunteers measurements were performed after 15 minutes of bed rest, avoiding any muscular
contractions.
In figure 1 schematic StO2 measurement line-drawing during UIRT is presented. The following
parameters were obtained: basal StO2 (%): basal StO2 before cuff inflation (maximal thenar
muscle StO2 was found by moving probe over thenar prominence); StO2 downslope during cuffing
(∆downStO2)%/sec); StO2 upslope (∆upStO2)%/sec) after cuffing release; overshootStO2 (%):
maximal StO2 after cuffing release. Inspectra measures content of hemoglobin in sample volume
of underlining tissue - Tissue Haemoglobin Index (THI). Average of muscle THI before and at
the end of cuff inflation was reported. These data were automatically obtained using the
Inspectra Analysis Program V2.0 (Hutchinson Technology Inc., USA) running in MatLab 7.0
(MathWorks Inc., USA). Estimation of muscle oxygen consumption (mVO2Nirs) and muscle oxygen
extraction ratio (mOER) were calculated using the following formulas:
mVO2Nirs= ΔdownStO2 * THI* (-1), mOER(%)= (1- basalStO2/overshootStO2)* 100.
Severity of disease Sepsis-related Organ Failure Assessment (SOFA score) was calculated at
the time of each measurement to asses the level of organ dysfunction. Dobutamine,
norepinephrine requirement represented the dose of drug during the Sto2 measurement. Used of
levosimendan is reported if patient received the drug less then a week before inclusion in
the study. Use of intra-aortic balloon pump during ICU stay is reported.
Laboratory analysis Blood was withdrawn from superior vena cava approximately 2cm above right
atrium and pulmonary artery was performed at the time of each StO2 measurement to determine
ScvO2 (%) and SvO2(%) respectively. In view of the known problems arising during sampling
from pulmonary artery, including the possibility of contaminating artery blood with pulmonary
capillary blood, all samples from this site were withdrawn over 30s, using a low-negative
pressure technique, and never with the balloon inflated . A standard volume of 1mL of blood
was obtained from each side after withdrawn of dead-space blood and flushing fluid. All
measurements were made using a cooximeter (RapidLab 1265, Bayer HealthCare, Germany).
Plasma lactate concentration was measured using enzymatic colorimetric method (Lactate, Roche
Diagnostics, Germany) at the time of each StO2 measurement.
Data analysis StO2 curves were analyzed by Inspectra Analysis Program V2.0. Linear regression
was used to extrapolate the rate of Δdown- and Δup- StO2 during UIRT. Data was expressed as
median ± standard deviation (SD). Non parametric test: Kolmogorov-Smirnov, Wilcoxon and
Fisher exact test were used (SPSS 10.0 for Windows ™, SPSS Inc., USA). Spearman correlation
test was used to determine correlation. To compare muscle tissue StO2 variables during UIRT,
ScvO2 and SvO2: bias, systemic disagreement between the measurements (mean difference between
two measurements), and precision, the random error in measuring (standard deviation of bias),
were calculated. The limits of agreement were arbitrary set by Bland and Altman as the bias±
2 SD. To determine the variables independently associated with survival uni- and multivariate
logistic regression (Forward Stepwise (Likelihood Ratio)) was used. The p value of <0.05
(2-tailed) was considered statistically significant.
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