1. Monitoring global volume-related hemodynamic or regional
variables after initial resuscitation: What is a better predictor of
outcome in critically ill septic patients?*
Martijn Poeze, MD, PhD; Barbara C. J. Solberg; Jan Willem M. Greve, MD, PhD;
Graham Ramsay, MD, PhD, FRCS
Objective: Regional variables of organ dysfunction are thought dioxide pressure, gastric mucosal pH, mucosal-end tidal PCO2
to be better monitoring variables than global pressure-related gap, indocyanine green blood clearance, indocyanine green
hemodynamic variables. Whether a difference exists between plasma clearance, and plasma disappearance rate. Multivari-
regional and global volume-related variables in critically ill pa- ate analysis identified lactate, gastric mucosal pH, mucosal-
tients after resuscitation is unknown. end tidal PCO2 gap, mucosal-arterial PCO2 gap, indocyanine
Design: Prospective diagnostic test evaluation. green plasma clearance, and plasma disappearance rate of dye
Setting: University-affiliated mixed intensive care unit. as nondependent predictors of outcome. Patients who subse-
Patients: Twenty-eight critically ill patients. quently died had a significantly lower gastric mucosal pH,
Interventions: Using standardized resuscitation, hemodynamic higher intramucosal carbon dioxide pressure and mucosal-end
optimization was targeted at mean arterial pressure, heart rate, tidal PCO2 gap, and lower indocyanine green blood clearance,
occlusion pressure, cardiac output, systemic vascular resistance,
indocyanine green plasma clearance, plasma disappearance
and urine output. Primary outcome variable was in-hospital mor-
rate, and right ventricular end-diastolic volume index, of which
tality.
gastric mucosal pH, mucosal-end tidal PCO2 gap, and indocya-
Measurements and Main Results: During resuscitation,
global volume-related hemodynamic variables were measured nine green blood clearance were the most important predictors
simultaneously and compared with regional variables. At ad- of outcome.
mission no variable was superior as a predictor of outcome. Conclusions: Initial resuscitation of critically ill patients
During resuscitation, significant changes were seen in mean with shock does not require monitoring of regional variables.
arterial pressure, central venous pressure, oxygen delivery, After stabilization, however, regional variables are the best
systemic vascular resistance, total blood volume, right heart predictors of outcome. (Crit Care Med 2005; 33:2494–2500)
and ventricle end-diastolic volume, right ventricle ejection KEY WORDS: sepsis; monitoring; predictor; outcome; tonometry;
fraction, right and left stroke work index, intramucosal carbon indocyanine green
T he ability to recognize the fea- tent of shock has been identified as an Therefore, there is a need for other
tures of shock is crucial in the important contributory factor leading to indicators of tissue oxygenation in pa-
management of critically ill a considerable number of “preventable” tients with shock, which are more sensi-
patients. In trauma patients, deaths (1). The standard resuscitation tive and specific than the global pressure-
failure to recognize the presence or ex- during therapy for shock is aimed at cor- related variables. Two techniques have
recting global pressure-related variables. been introduced that may be able to de-
However, correcting these variables pro- tect occult hypovolemia.
*See also p. 2691.
duces variable outcomes in critically ill It has been suggested that measuring
From the Department of Surgery (MP, JWMG, GR) patients. There are several possible rea- regional variables of splanchnic perfusion
and Intensive Care Medicine (BCJS), University Hospi- sons for this variability. The recognition is a better predictor of the presence of
tal Maastricht, The Netherlands. of shock may be hampered by the pa- uncompensated shock than markers of
Supported, in part, by the University Hospital tients’ compensatory capacities. A patient global perfusion (5, 6). Splanchnic perfu-
Maastricht Research Fund, Maastricht, The Nether-
lands. may be in shock despite having a normal sion seems to play an important role dur-
There are no financial disclosure for any of the heart rate and blood pressure. Moreover, ing shock and resuscitation. Recent stud-
authors. the therapy used to treat shock can nor- ies suggest the presence of a disturbed
Address requests for reprints to: M. Poeze, MD, malize variables by which shock is as- splanchnic circulation in apparently
PhD, Department of Surgery, University Hospital Maas-
tricht, P. Debyelaan 25, NL-6202 AZ Maastricht, The
sessed clinically, even though defective compensated shock (7–9). Critically ill
Netherlands. tissue oxygenation may still exist (2– 4). patients with a persistently inadequate
Copyright © 2005 by the Society of Critical Care Global pressure-related variables may be splanchnic perfusion are at increased risk
Medicine and Lippincott Williams & Wilkins too inaccurate to detect these abnormal- of developing multiple organ failure dur-
DOI: 10.1097/01.CCM.0000185642.33586.9D ities. ing their intensive care stay (10, 11).
2494 Crit Care Med 2005 Vol. 33, No. 11

2. Another option is measuring the Society of Critical Care Medicine consensus the greatest volume available, as has been de-
global volume-related variables (such as conference criteria were included (17). In the scribed in detail (19). The following variables
extravascular lung water volume or in- presence of clinically suspected or proven in- were determined: right heart- and right ven-
trathoracic blood volume) instead of fection, patients were defined as having sepsis. tricular end-diastolic volume index, right ven-
A clinical suspicion of infection was defined as tricular ejection fraction (RVEF), right ven-
pressure-related variables. A considerable
the presence of abnormalities on radiograph of tricular end-systolic volume index, right
number of studies have indicated the lack ventricular stroke work index, left heart end-
of relation between the degree of hypovo- the thorax consistent with pulmonary infec-
tion, peritonitis confirmed at surgery or clin- diastolic volume index, global end-diastolic
lemia and the pressure-related variables volume index, extravascular lung water index,
ical examination, or positive Gram-negative
(12, 13). Instead, the use of volume- intrathoracic blood volume index, total blood
stain for infection. All patients were ventilated.
related global hemodynamic variables is volume index, and pulmonary blood volume
Patients were included if their Acute Physiol-
thought to indicate the presence of hypo- index.
ogy and Chronic Health Evaluation (APACHE)
volemia (14 –16). Regional Hemodynamic Function Vari-
II score was 12 (18). ables. ICG clearance measurements (ICG
In view of these observations, we car- Patients with sepsis-induced hypotension
ried out a prospective trial in which crit- blood clearance [CBI], ICG plasma clearance
or severe sepsis who were expected to die [CPI], and plasma disappearance rate of dye
ically ill septic patients with or without within the first 24 hrs were not included. [PDR]) were performed using the ICG bolus
overt clinical shock underwent standard- Patients on dialysis at admission were also infusion method. The PDR rate was deter-
ized resuscitation to normalize their excluded from participation. mined from the linear elimination curve of
global pressure-related hemodynamics. ICG through the liver. CBI and CPI were cal-
The responses of both the global volume- culated by multiplying the PDR by the TBV
related hemodynamic and the regional Measurements of Systemic and (and [1 hematocrit] for the CPI).
variables to this resuscitation were eval- Regional Variables Gastric tonometry measurements (PrCO2,
uated in terms of their predictive value mucosal-end tidal PCO2 gap [Pr-etCO2-gap], and
for mortality. Our hypothesis was that After inclusion, patients received a 3-Fr mucosal-arterial PCO2 gap) were measured at
resuscitation in the intensive care unit thermistor-tipped fiberoptic catheter (PV 10-min intervals using gas-automated capnog-
2024, Pulsion Medical Systems, Munich, Ger- raphy (Tonocap, Datex-Ohmeda) (20). The
(ICU) could be aimed at the global vol-
many) placed into the descending aorta via a PCO2 and pH values of the blood gases were
ume-related variables, but that after nor- corrected for the central blood temperature
4-Fr introducing sheath (Arrow, Reading, PA)
malization, optimal resuscitation would measurements, using the formulas provided
in the femoral artery. The catheter was then
only be achieved using regional variables. by the manufacturer (ABL 100, Radiometer,
connected to a bedside monitor (COLD Z-021,
Pulsion Medical Systems, Munich, Germany). Kopenhagen).
PATIENTS AND METHODS In addition, a pulmonary artery thermodilu-
tion catheter (7.5-Fr, Baxter) was introduced Resuscitation Protocol
Study Design and also connected to the COLD bedside mon-
itor. A gastric tonometry catheter (14-Fr, Da- Resuscitation was aimed at improving
This study was conducted as a prospective tex Ohmeda, Finland) was introduced for mea- global pressure-related hemodynamics as
evaluation of the predictive value of global surement of intramucosal carbon dioxide judged by the intensivist on call: in general,
pressure- and volume-related hemodynamic pressure (PrCO2) using the gas-automated circulatory support was titrated to increase
and regional variables of splanchnic perfusion capnograph (Tonocap TC-200, Datex-Ohmeda, the MAP 70 mm Hg, systemic vascular re-
during the intensive care resuscitation of crit- Finland). Gastric mucosal pH (pHi) was calcu- sistance 1100 dyne/sec/cm5, CI 2.5 L/min/
ically ill septic patients. In-hospital mortality lated using the standard Henderson-Hassel- m2, and urine output 0.5 mL/kg/hr. If these
was used as the primary end point. bach formula (19). At admission to the ICU, criteria were not met and PAOP was 18 mm
The study protocol prospectively defined several variables were obtained to evaluate dis- Hg, patients received a fluid challenge of 500
that the effects of the resuscitation should be turbances in hemodynamics and organ func- mL or 1000 mL (depending on blood pressure)
analyzed according to the prognostic values. tion. These variables could be divided into saline 0.9% and/or Gelofusine (Braun, Mel-
After inclusion, a baseline assessment was per- three groups. sungen, Germany). If this caused an increase
formed. Baseline variables were evaluated for Routine Global Hemodynamic Variables. in CI and/or MAP 10% with the PAOP re-
their ability to predict outcome. After resusci- Using a central arterial and a pulmonary ar- maining 18 mm Hg, another fluid challenge
tation, the hemodynamic variables were as- tery flotation catheter, we measured mean ar- could be given. If the increase in CI or MAP
sessed a second time and the prognostic value terial pressure (MAP), heart rate, pulmonary was 10%, then fluid challenging was
of these variables was assessed again at this artery occlusion pressure (PAOP), and cardiac stopped, regardless of PAOP. After fluid chal-
time point. index (CI). Mixed venous and arterial blood lenging, dobutamine or noradrenaline (21, 22)
Patients fulfilling the inclusion criteria gases were used to measure lactate and to or both were given guided by the effects on CI
were included during a period of 2 yrs from a calculate oxygen delivery and oxygen con-
and MAP, aiming at CI 2.5 L/min/m2 and
mixed ICU at a university hospital. The Insti- sumption and were drawn simultaneously
MAP 70 mm Hg. If PAOP was 18 mm Hg,
tutional Review Board of the hospital approved with the thermodilution measurement. The
dobutamine was given primarily. Whenever
global hemodynamic variables were used to
this study. Written informed consent was ob- hematocrit was 0.3, a transfusion of packed
calculate the systemic vascular resistance in-
tained from each patient’s next of kin, since all red cells was allowed. The intensivists were
dex. Urine output was measured using a Foley
patients were ventilated and sedated at the blinded for the results of the regional tono-
urinary catheter.
time of inclusion in the study. Global Volume-Related Hemodynamic metric and ICG-dilution variables.
Variables. Double dilution measurements A stable hemodynamic status was defined
Study Patients were performed using a 10-mL cold bolus in- by the intensivist using the following guide-
fusion of 1 mg/kg indocyanine green (ICG) in lines: MAP 70 mm Hg, or a stable blood
Critically ill patients with sepsis as defined saline. The principle of these measurements is pressure (variation in MAP 10 mm Hg, heart
by the American College of Chest Physicians/ based on the distribution of an indicator over rate 30%) during 2 hrs without the necessity
Crit Care Med 2005 Vol. 33, No. 11 2495

3. Table 1. Patient demographics
Variables Total Group Nonsurvivor Survivor p Value
Number 28 14 14
Age, yrs 64 13 68 14 60 12 .1
Gender, % female 39 36 43 .5
Bacteriologically proven sepsis, n 17/28 9/14 8/14 .5
Suspected source of sepsis, n (%)
Abdominal 7 (25) 3 (21) 4 (29)
Pulmonary 17 (61) 9 (64) 8 (57)
Other 4 (14) 2 (14) 2 (14) .8
Medical/surgical 8/20 5/9 3/11 .4
APACHE II score 17.7 4.9 18.4 5.3 16.6 4.1 .2
MOF score 5.5 1.8 6.1 2.1 4.8 1.2 .3
APACHE, Acute Physiology and Chronic Health Evaluation; MOF, multiple organ failure.
Data are presented as mean SD or as percentages. The p value indicates the significance level for the comparison between surviving and nonsurviving
patients.
of increasing any vasopressor or inotropic namic variables, with survival as the fixed Admission Variables
therapy or without the need of fluid adminis- factor and time (resuscitation period) as co-
tration to treat a decrease in MAP of 10 mm variate, presented as nonstandardized regres- At admission to the ICU, before ICU
Hg or a change in heart rate of 30%. sion coefficients (B) (with SE). resuscitation was initiated, nonsurviving
This definition was used to divide the study To detect the most important predictors of patients had a significantly lower MAP
period into two periods: a period from admis- mortality, hemodynamic variables were ana- (Table 2) as well as a significantly lower
sion to stabilization and a period after stabili- lyzed using a logistic nonparametric multiple RVEF and higher lactate. Moreover, these
zation. Although the periods before and after regression model (backward conditional). The patients had a significantly lower CBI and
stabilization were seen as two distinct periods, validity of the different tests was evaluated by CPI, as well as a lower PDR (Table 2). The
the same goals for resuscitation were actually means of a method for comparing areas under
gastric pHi was significantly lower in the
used as a continuum in the primary and sec- the receiver operating characteristic (ROC)
nonsurviving patients, with a higher
ondary phases. After stabilization had been curves (AUCs), as previously described in de-
PiCO2, Pr-etCO2, and mucosal-arterial
achieved, the previously mentioned measure- tail (23, 24). AUCs were calculated for the
ments were repeated. variables at admission and after stabilization.
PCO2 gap. Variables of global perfusion
None of the patients were enterally fed The odds ratios for the variables after stabili- and regional function were both different
during the study period. H2-blockers were zation were calculated using the optimal cut- between the two patient groups. None of
given routinely, using ranitidine. Antibiotics off point derived from the ROC curves. The the global or regional variables at admis-
were given blindly or directed at identified optimal cutoff value for predicting mortality sion were more important in predicting
organisms. was calculated as the point with the greatest mortality than another variable on ROC
combined sensitivity and specificity. For these curve analysis, although gastric pHi and
Follow-Up analyses, a p .05 was considered statistically CPI tended to be more important predic-
significant. tors of mortality on logistic regression
Patients’ follow-up was continued during analysis (p .06 and p .09 for pHi and
the remainder of the ICU admission. After RESULTS CPI, respectively).
discharge from the ICU, patients were moni-
tored for 28 days or until final hospital dis-
Patients
charge, whichever was longer, for morbidity Changes During Resuscitation
and mortality. A total of 28 patients with severe sep-
sis or septic shock were included in the Before the protocolized resuscitation
Statistics analysis and monitored prospectively (Ta- (i.e., before admission to the ICU), pa-
ble 1). The presence of infection was con- tients had received a mean of 4.4 L of
Data were analyzed using the SPSS (ver- firmed in 17 patients. The mean APACHE saline and 3.3 L of Gelofusine, with no
sion 7.5) software program (SPSS, Chicago, significant difference in volume infused
II score at admission was 17.7. The me-
IL). Data from patient characteristics were as-
dian time between the start of the symp- between the patients with and without
sessed using Student’s t-test and the chi-
toms and admission to the ICU was 18 sepsis-induced hypotension. This amount
square test. Admission variables were assessed
hrs. Of the 28 patients, 12 were admitted of fluids was given during the admission
using one-way analysis of variance. Data dur-
ing the resuscitation period were compared in shock (systolic blood pressure 90 days before ICU admission (median 2.0
using the Mann-Whitney U test. The use of the mm Hg or sustained drop of 40 mm days, range 0 –95 days).
multiple comparisons may have introduced Hg). There were no differences between During this resuscitation phase, MAP,
type I errors. The use of a Bonferroni correc- survivors and nonsurvivors with respect oxygen delivery, and RVEF were in-
tion for the multiple comparisons leads to a to age, gender, duration of complaints creased significantly for all patients taken
corrected alpha value of .002. before inclusion, number of patients with together (p .002, p .05, and p .02
A multivariate procedure was used to pro- sepsis and sepsis-induced hypotension, for MAP, oxygen delivery, and RVEF, re-
vide a regression analysis and analysis of vari- APACHE II, scores or multiple organ fail- spectively). Lactate values were signifi-
ance for the multiple dependent hemody- ure scores. cantly decreased.
2496 Crit Care Med 2005 Vol. 33, No. 11

4. Table 2. Global and regional hemodynamics at admission in survivors and nonsurvivors dynamic variables. Third, resuscitation
aimed at improving global hemodynam-
Variables Survivors Nonsurvivors p Values
ics did improve global pressure-related
Global pressure-related variables
and oxygen transport variables but not
MAP 78 13 70 12 .04a volume-related global hemodynamic and
CVP 11 3 12 4 .3 regional variables.
DO2I 635 197 572 135 .2 Previously, only a few studies have
SVRI 1242 413 1217 528 .8 compared the predictive power of gastric
PAOP 14 3 15 6 .4
Global volume-related variables tonometric variables with systemic he-
TBVI 3708 1188 3719 821 1.0 modynamic variables. Bams et al. (25)
RHEDVI 467 218 459 170 .9 determined the predictive value of gastric
RVEDVI 172 54 189 60 .4 pHi in cardiac surgical patients. In con-
RVSWI 9.1 3.8 10.1 3.9 .3
LVSWI 39.0 14.0 33.1 17.6 .2
trast to our study, they found the mean
RVEF 25.5 6.3 21.2 8.1 .04a arterial pressure and mean pulmonary ar-
Regional variables terial pressure to be more predictive of
pHi 7.34 0.08 7.24 0.1 .03a mortality than gastric pHi or PrCO2 when
PrCO2 5.7 1.0 6.7 2.3 .03a measured at admission and after 12 hrs.
Pr-etCO2 1.9 1.0 2.6 1.8 .05
Pr-aCO2 0.9 0.7 1.5 1.4 .045a The difference between our study and
CBI 837 420 550 368 .02a their study may be related to the patient
CPI 587 317 388 262 .03a population selected, whereas another ex-
PDR 21.0 9.9 14.9 8.0 .03a planation for the differences might be the
UP 1.3 1.4 1.2 1.2 .8
Lactate 1.2 0.6 2.3 1.9 .007a
presence of extrasplanchnic perfusion ab-
Base deficit 2.7 7.2 3.6 6.2 .6 normalities, such as decreased bicarbon-
ate content. However, this cannot explain
MAP, mean arterial pressure (mm Hg); CVP, central venous pressure (mm Hg); DO2I, oxygen the predictive power of the PrCO2 and the
delivery index (mL/min/m2); SVRI, systemic vascular resistance index (dyne/sec/cm5); PAOP, pulmo- Pr-etCO2 in our study. What is perhaps
nary artery occlusion pressure (mm Hg); TBVI, total blood volume index; RHEDVI, right-heart more important is the fact that in our
end-diastolic volume index; RVEDVI, right ventricle end-diastolic volume index; RVSWI, right ventri- study, gastric tonometric variables be-
cle stroke work index (g/m/m2); LVSWI, left-ventricle stroke work index (g/m/m2); pHi, gastric
came predictive after stabilization had
intramucosal pH; PrCO2, regional (gastric) PCO2 (kPa); Pr-etCO2, difference between regional and
end-tidal PCO2; Pr-aCO2, mucosal-arterial PCO2; CBI, indocyanine green blood clearance (mL/min/m2);
been achieved, usually 12 hrs after ad-
CPI, indocyanine plasma clearance (mL/min/m2); PDR, indocyanine plasma disappearance rate (%); mission. This is confirmed by the results
UP, urine output (mL/kg/hr). obtained by Maynard et al. (26), who
a
p .05. Data are presented as mean SD. found a high predictive value for the gas-
tric pHi after only 3 days. On the other
hand, Lorente et al. (27) found that the
Patients presenting at the ICU in an tidal PCO2 gap, and PrCO2 (CBI, regres- mucosal-arterial PCO2 gap was an inde-
early phase of sepsis (duration of com- sion coefficient B 0.002, SE 0.0007, pendent predictor of outcome in severe
plaints 0 –12 hrs) had a significant in- p .01; pHi, B 10.9, SE 4.6, p burn patients only at admission and not
crease in RVEF, unlike patients present- .02; PrCO2, B 1.5, SE 0.7, p .03; after 12 hrs of resuscitation. Another
ing in a late phase ( 24 hrs). Pr-etCO2, B 1.5, SE 0.7, p .02; study found that gastric PrCO2 and sys-
constant, B 83.9, SE 35.1). The AUCs temic lactate were both good predictors
Hemodynamic Variables After of gastric pHi and Pr-etCO2 were signifi- of outcome in patients with severe sepsis
Stabilization as Predictors of cantly higher after stabilization than at (28). Similarly, Ivatury et al. (29) indi-
Mortality admission and were significantly higher cated that gastric pHi was the best pre-
than the AUCs of MAP, PrCO2, central dictor of outcome in severely traumatized
After patients had been stabilized, the venous pressure, left ventricular stroke patients with organ failure. Thus, several
global volume-related hemodynamic and work index, and arterial pH (Table 4). studies have confirmed the importance of
regional variables were compared be- gastric intramucosal tonometry in pre-
tween surviving and nonsurviving pa- DISCUSSION dicting outcome during the resuscitation
tients. After stabilization, patients who of critically ill patients.
died during their hospital stay had a sig- There were three main findings of this The importance of volume-related
nificantly higher PrCO2 and Pr-etCO2 and study. First, no superior predictor of out- global hemodynamic variables in the as-
a significantly lower CBI, CPI, PDR, and come was identified at admission, al- sessment of intravascular volume status
pHi (Table 3). though both regional variables and global has been emphasized before. Numerous
All variables were subsequently used hemodynamic variables were different be- studies have indicated that intravascular
as independent variables in a logistic re- tween surviving and nonsurviving pa- volumes assessed by the thermo-dye di-
gression analysis with mortality as the tients, and the mean values were abnor- lution technique give more accurate in-
dependent variable, and areas under the mal in both groups compared with formation on the preload dependency of
ROC curves were calculated. The most normal values. Second, after stabiliza- cardiac output than pressure-related vari-
powerful predictors (in terms of signifi- tion, regional variables were the most ables (15, 30 –34). In addition to this, our
cant regression coefficients) were CBI, important predictors of mortality com- study investigated the predictive power of
gastric intramucosal pHi, mucosal-end- pared with global volume-related hemo- the global volume-related variables in pa-
Crit Care Med 2005 Vol. 33, No. 11 2497

5. tients with septic shock. We found that achieved higher oxygen transport and A number of comments need to be
volume-related hemodynamic variables perfusion variables during their stay at made on the interpretation of our obser-
were superior to pressure-related vari- the intensive care unit. In addition, vations. The resuscitation principles used
ables in differentiating between survivors Moore et al. (1) found that in critically ill in this study were based on standard
and nonsurvivors. Previously, Jaarsma et trauma patients, the inability to improve practice at our ICU, and the intensivist on
al. (35) found that the predictive power of oxygen transport during resuscitation call judged whether the resuscitation led
left ventricular stroke work index using aimed at achieving supranormal oxygen to stabilization of the global hemodynam-
echocardiography was higher than that of delivery was related to the development ics. Although this practice led to im-
PAOP in patients with acute myocardial of multiple organ failure. However, it re- provement of global hemodynamic vari-
infarction. In our study, resuscitation in- mained difficult to identify the individual ables, no improvement or even a
creased RVEF in both surviving and non- worsening of the regional variables was
patient who was prone to develop multi-
surviving patients, indicating that resus- noted. It may be questioned whether the
ple organ failure or die on intensive care.
citation improves global perfusion in all resuscitation used was adequate and
Rhodes et al. (37) described a dobutamine
patients. It is interesting to see that the whether other methods of resuscitation
extravascular lung water tended to de- stress test that can identify nonsurvivors.
Creteur et al. (38) found that this stress should have been attempted. The use of
crease during resuscitation. This de-
test identifies occult hypovolemia in the thermodilution catheters to improve he-
crease in extravascular lung water may
splanchnic area. In addition, our study modynamics during sepsis is controver-
indicate improved fluid balance or may be
found that patients with shock at admis- sial, and some studies have indicated that
due to the increased application of posi-
sion had obvious abnormalities in both the use of these catheters to treat hemo-
tive end-expiratory pressure ventilation
(36). global, gastric tonometric, and ICG- dynamic disturbances during critical ill-
Intensive care resuscitation is aimed clearance variables, whereas abnormali- ness may increase mortality rate (39, 40).
at improving the global perfusion. Bishop ties in the hepatosplanchnic variables However, our aim was to study the effects
et al. (2) described that surviving patients still persisted after stabilization. of the resuscitation techniques normally
used at an ICU. The tendency of the
global volume-related variables stroke
Table 3. Global hemodynamic and regional variables after stabilization in surviving and nonsurviving volume and RVEF to improve and the
patients
significant improvement in oxygen deliv-
Variables Survivors Nonsurvivors p Value ery during this resuscitation indicate that
the resuscitation led to improvement of
pHi 7.31 0.07 7.24 0.09 .03 the global hemodynamics. The question
Pr-etCO2 2.1 0.7 3.1 1.5 .04 which resuscitation techniques should be
PrCO2 6.0 0.8 7.1 1.5 .04
CBI 838 295 572 262 .02
applied in patients with septic shock re-
CPI 587 224 411 168 .02 mains difficult to answer. The use of “su-
PDR 21.1 7.1 14.6 5.0 .01 pranormal” hemodynamic goals in pa-
tients with septic shock and organ failure
pHi, gastric intramucosal pH; Pr-etCO2, difference between regional and end-tidal PCO2; PrCO2, has been shown to have no influence on
regional (gastric) PCO2 (kPa); CBI, indocyanine green blood clearance (mL/min/m2); CPI, indocyanine
outcome (41, 42) and even increased
plasma clearance (mL/min/m2); PDR, indocyanine plasma disappearance rate.
Data are presented as mean SD. Only variables that showed a significant difference were
mortality rate in some studies (43). In a
displayed. Comparison between variables after stabilization was achieved between survivors and recent trial, the application of these su-
nonsurvivors. pranormal goals early in the course of
Table 4. Area under the receiver operating characteristic curves (AUC) and odds ratios
Variable Admission AUC After stabilization AUC Cutoff Points Odds Ratio 95% CI
CBI 0.69 0.08 0.70 0.08a 533 3.9 1.1–13.8b
MAP 0.55 0.05 0.57 0.06 78 0.8 0.3–1.8
pHi 0.65 0.05 0.75 0.05b,c 7.17 4.8 1.5–14.6b
PrCO2 0.56 0.05 0.65 0.06 5.8 2.0 0.9–4.5
Pr-etCO2 0.61 0.06 0.75 0.07b,c 1.8 3.0 1.4–6.3b
Pr-aCO2 0.59 0.06 0.67 0.09 0.83 1.3 0.6–3.0
CVP 0.57 0.06 0.56 0.08 12 0.8 0.2–2.9
LVSWI 0.62 0.06 0.60 0.08 37 1.8 0.6–5.6
Arterial pH 0.63 0.06 0.63 0.08 7.35 2.1 0.7–6.2
CBI, indocyanine green blood clearance (mL/min/m2); MAP, mean arterial pressure (mm Hg); pHi, gastric intramucosal pH; PrCO2, regional (gastric)
PCO2 (kPa); Pr-etCO2, difference between regional and end-tidal PCO2; Pr-aCO2, mucosal-arterial PCO2; CVP, central venous pressure (mm Hg); LVSWI,
left-ventricle stroke work index (g/m/m2); CI, confidence interval.
a
p .05 for CBI vs. CVP; bp .05 for the time point after stabilization vs. the time point at admission; cp .05 for comparison of pHi or Pr-etCO2 vs.
MAP, PrCO2, CVP, LVSWI, and arterial pH. Values are AUC SE. Data indicate the differences in AUC at admission and after stabilization. The maximum
value for the AUC is 1. No differences in AUC were present at admission. The AUC values of pHi and Pr-etCO2 were significantly larger after stabilization
compared to admission values. The odds ratios represent the increased risk of death for an optimal cut-off point of the test defined by analysis of the
ROC-curves.
2498 Crit Care Med 2005 Vol. 33, No. 11

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