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Comparison of fluid compartments and fluid responsiveness in septic and non-septic patients.

Patients with septic shock release mediators which increase microvascular permeability and produce effusion of fluids and proteins to the interstitial space, causing hypovolaemia, hypoproteinaemia, pulmonary oedema, peripheral oedema and multi-organ failure (1-3). The primary goal for resuscitation is to re-establish adequate haemodynamics and micro-circulatory perfusion. Early aggressive resuscitation has shown great efficacy (4). However, fluid resuscitation can increase hydrostatic pressure, inducing accumulation of interstitial fluid and worsening of tissue oedema. Once the initial phase is over, it is very important to identify the patient's intravascular volume to optimise fluid therapy.

Abnormalities of intravascular volume cannot be accurately measured using haematocrit or static preload indicators (central venous pressure or pulmonary artery occlusion pressure) (5), and therefore some authors have used the intrathoracic blood volume index (ITBVI) and the extravascular lung water index (EVLWI), obtained using the transpulmonary thermodilution technique (6,7). Other authors have used the initial distribution volume of glucose (IDVG) to assess volume status (8).

These volumes are better indicators of cardiac preload; however, not all low cardiac preloads imply that fluid loading will be beneficial, so dynamic measurements have been recommended. In patients with an increase in permeability, fluid loading can only transiently improve haemodynamic parameters, and soon a high percentage of administered fluid leaves the intravascular compartment and enters the interstitial space. Increases in interstitial fluid may not only cause pulmonary oedema, but they also represent an independent risk factor for poor outcomes (3,9). Previous studies have shown different responses to fluid loading (10-12).

The purpose of our study was to assess the redistribution of fluids and the differential response to volume in patients with sepsis, compared with a control group. We used hydroxyethyl starch due to its greater volume expansion effect and longer intravascular persistence compared to crystalloids (13). As there are slow- and fast-mixing fluid compartments, we waited 75 minutes to measure the volume changes produced in response to a fluid load. We used transpulmonary thermodilution to measure the EVLWI, ITBVI and pulmonary blood volume (14,15). For the measurement of the IDVG (16,17), plasma volume (PV) (18) and extracellular water (ECW) (19), we used dilutions of glucose, indocyanine green and sinistrin, respectively.

The aim of this study was to measure the response to a fluid load in patients with and without septic shock and its relationship with baseline fluid distributions and with the various compartment ratios. Specifically, we explored the usefulness of the systemic permeability ratio (interstitial/PV) as a guide for fluid therapy. This ratio represents basal redistribution and may show the degree of systemic vascular permeability and may therefore predict what percentage of the intravascular volume will be lost. This calculation could be an alternative method of optimising fluid therapy in septic patients. We also studied whether this ratio can predict the increase in intrathoracic blood volume after fluid loading (a higher ratio would indicate more permeability and less retention of the fluid loaded might be expected).

We hypothesised that there are fluid redistributions in patients with septic shock, that fluid loading increases the intravascular volume only slightly and this is related to the systemic permeability ratio.

MATERIALS AND METHODS

Study population

We conducted a prospective and comparative clinical study of a series of adult patients admitted to our intensive care unit (30-bed intensive care unit of a tertiary medical centre) between September 2005 and January 2007. This study was approved by the institutional ethics committee and conducted with written informed consent from the patients' relatives and next of kin and in accordance with the Declaration of Helsinki of the World Medical Association. The inclusion criteria were age between 18 to 80 years and a need for arterial cannulation for blood pressure monitoring or for extraction of arterial blood gas. The exclusion criteria were allergy to any indicators, pregnancy, blood glucose >16 mmol/l, renal replacement therapy, prior increase of ECW (ascites or pitting oedema >2 mm), situations in which transpulmonary dilution does not provide appropriate information and cases of poor peripheral perfusion and/or oxygen saturation of under 92% (which prevents correct pulse densitometry).

We enrolled 32 critical patients and studied their clinical parameters (blood pressure and heart rate), laboratory parameters (haematocrit, leukocytes, total protein and C-reactive protein) and various distribution volumes. The sepsis group included 18 patients who met the criteria for septic shock according to the consensus conference of the American College of Chest Physicians and Society of Critical Care Medicine (20). The main sepsis criterion was infection associated with hypotension after volume replacement, along with perfusion abnormalities such as lactic acidosis or oliguria. Patients were studied within the first 36 hours after meeting the septic shock criteria. Fluid loading was undertaken to achieve a mean arterial pressure greater than 70 mmHg and a cardiac index (CI) greater than 3.0 l/min/[m.sup.2]. We started infusing 1000 ml of crystalloid and 500 ml of colloid. If hypotension persisted, noradrenaline infusion was started, and transpulmonary dilution using a PiCCO[R] monitor (Pulsion Medical System, Munich, Germany) was performed. We continued infusing fluids in addition to noradrenaline if ITBVI <900 ml/[m.sup.2] and EVLWI <10 ml/kg. Once an ITBVI greater than 900 ml/[m.sup.2] was reached, or in the presence of an EVLWI greater than 10 ml/kg, the administration of fluid was ceased, and only noradrenaline therapy was administered associated with dobutamine, depending on the cardiac index. The patients' haemodynamics were judged to be clinically stable at the time of the study. Stability was defined as no fluid challenge and no change in inotropes or vasopressor doses for two hours. The control group included 14 patients who had pathologies not related to sepsis or alterations in vascular permeability and who had a clinical indication for an arterial catheter. Monitoring by means of PiCCO, which provides haemodynamic data, was performed on those patients.

Procedures

Measurement of intrathoracic blood volume, pulmonary blood volume and extravascular lung water

These measurements were performed by means of transpulmonary dilution, using PiCCO and PiCCOPlus monitors. A thermistor, placed into a femoral arterial catheter, measured downstream temperature changes induced by the injection of 20 ml of a cold (below 18[degrees]C) saline solution bolus into the superior vena cava. Volumes were calculated from the mean transit time and the exponential downslope time of the transpulmonary thermodilution curve (7). Measurements were performed in duplicate, irrespective of ventilatory cycle, and were averaged.

Measurement of the circulating blood volume and plasma volume

These measurements were performed by injecting indocyanine green and by measuring arterial concentration changes by means of pulse densitometry using the LiMON[R] monitor (Pulsion Medical System PC5000, Munich, Germany). This method uses two wavelengths and permits continuous determination of plasma concentrations (at every heart beat). The circulating blood volume (CBV) was calculated by dividing the quantity of indocyanine green administered (0.5 mg/kg) by the concentration of dye, computed by back-extrapolation of the clearance curve. We calculated the plasma volume starting from CBV: PV=CBVx (1 - Haematocrit/100) (21,22).

Measurement of extracellular water

Sinistrin is a polyfructose inulin analogue, which is transported almost exclusively by diffusion. We infused 5 g of sinistrin (Inutest[R] 25%, 25 ml, Laevosan, Austria) for 30 seconds through the central venous catheter and serial blood samples were drawn through an indwelling arterial catheter immediately before and at 2.5, 5, 7.5, 10, 15, 30, 60, 120, 150, 180 and 210 minutes after the completion of the sinistrin infusion. The sinistrin was analysed using chemical methods, adding anthrone, taking an absorbency reading at 623 nm and subtracting the baseline absorbency. We transferred the absorbency values in the concentrations using a calibration curve. Then, using the changes in concentration during this time, we created a plasmatic disappearance curve, which was studied in a semilogarithmic way and by means of a non-compartmental approach, in order to calculate the ECW (23-25). The interstitial volume was calculated by subtracting the PV from the ECW.

Measurement of initial distribution volume of glucose

The fast distribution volume of glucose is not altered by insulin and it includes the plasma volume and extracellular water of highly perfused organs. IDVG was measured as explained by Hirota: infuse 25 ml of 20% glucose (5 g) through the central venous catheter for 30 seconds and take samples from the arterial catheter beforehand and at three minutes, using the formula:

IDVG=24.44 x [e.sup.-0.0298 x [DELTA]GL + 2.70

where [DELTA]GL is the increase in glucose at three minutes (26). The plasma concentration of glucose was determined using a blood analyser (RAPIDLab[R] 1265, Bayer Health Care, UK), which was calibrated several times a day. Each value was measured in duplicate and was averaged.

Fluid loading

After baseline measurements, the patients who had EVLWI <10 ml/kg and those with ITBVI <900 ml/[m.sup.2] or dehydration on clinical criteria (such as oliguria or dry lips and tongue and absence of oedema) received fluid loading with 7 ml/kg hydroxyethyl starch (HES 130/04 Voluven[R] Fresenius AG, Bad Homburg, Germany) (27). Fluids were given for 45 minutes, and haemodynamic and respiratory measurements, including ITBVI, pulmonary blood volume, EVLWI, [P.sub.a][O.sub.2]/Fi[O.sub.2] and CO, were repeated 30 minutes after completing the fluid load to allow time for redistribution into the slower compartments.

Calculation of ratios between compartments

The pulmonary vascular permeability index is the ratio of the EVLW to the pulmonary blood volume, and it reflects the state of permeability of the alveolar capillary barrier (14,16,28,29). Similarly, we used the ratio of total interstitial/intravascular compartment ([ECW-PV]/PV) as the systemic vascular permeability index (30).

Some studies have used the ratio of PV (measured with indocyanine green) and IDVG as an indicator of capillary leakage (8) because when there was a capillary leak, the measure of PV was overestimated due to indocyanine green binding to albumin effusion.

Finally, we calculated the percentage of fluids added that were retained in the intrathoracic blood volume: (increase in ITBVI after fluid loading/amount of fluid added) x 100.

Statistical analysis

All values are given as medians and interquartile ranges. Values were standardised as indices of body surface area (ITBVI) or pre-admission body weight (EVLWI, CBVI, ECWI and IDVGI). Volumes, indices and volume increases were compared between groups using the Mann-Whitney U test. The significance of the volume increase in each group was analysed using Wilcoxon's signed rank test. Correlations using the Spearman's rho regression analysis were also performed to determine the relationships among variables. The SPSS program, version 13.0 (SPSS Inc., Chicago, IL, USA), was used for the statistical analysis. A P value of <0.05 indicated statistically significant differences.

RESULTS

We studied 32 patients, including 19 women and 13 men, with an average age of 50[+ or -]18 years (21 to 79) and with no significant differences between groups. The Acute Physiology and Chronic Health Evaluation II score was 17[+ or -]5 (9-31) and was similar in both groups.

There were 18 patients in the septic group. All patients were kept on mechanical ventilation, and there were no differences between groups in respiratory parameters (tidal volume, PEEP, [P.sub.a][O.sub.2]/Fi[O.sub.2]). C-reactive protein was significantly higher in the septic group, and total protein was significantly higher in the control group. There were no significant differences between groups in other clinical or laboratory parameters. Table 1 shows the main clinical and laboratory characteristics of the patients.

The results of the transpulmonary dilution measurement in patients with sepsis revealed a lower ITBVI (P <0.003) without significant changes in the EVLWI. The average values for IDVG and CBV were similar in both groups, and ECW was greater in the septic group (Table 2).

Ten patients were excluded from the fluid loading test, three in the control group (one had an EVLWI of 14 ml/kg and two had oedema) and four in the septic group, who had oedema and EVLWIs between 14 and 19 ml/kg. We also excluded the results of the three patients in the septic group for whom we could not calculate ECW.

The remaining 22 patients (11 from the septic group and 11 controls) were fluid challenged. The 11 patients with sepsis showed lower basal ITBVIs (933 vs 1317 ml/[m.sup.2]) and lower increases in ITBVI (10 vs 145 ml/[m.sup.2] with P <0.003) (Figure 1). Haematocrit levels changed from 34.1 to 32.8% in septic patients and from 33.6 to 31.8% in non-septic patients. The median increase in IDGVI was 0.5 ml/kg (-276.0, -232.0), with no differences between groups and no linear correlation shown with the increases in ITBVI.

In the lungs, the ratio of interstitial water (EVLW) to intravascular pulmonary volume was greater in the septic group (P=0.003), due more to the low intravascular volume than to a high EVLWI (Table 3). The ratio of total interstitial volume (ECW-PV) to the intravascular volume (measured by PV) was also greater in the septic group. These ratios did not correlate among themselves (P=0.8). The PV/IDVG ratio showed no significant differences between groups. The ratios of compartments are shown in Table 3.

Lastly, after fluid loading, the percentage of fluids added that were retained in the intrathoracic blood volume was calculated. In septic patients, this percentage was much lower than in the control patients. This percentage was inversely correlated with the interstitial/PV ratio (rho -0.48, P=0.05), but this correlation disappeared when we considered only the group of septic patients (rho -0.20, P <0.6).

DISCUSSION

This study shows that, in the early stages of septic shock, there are differences in the distribution of fluids between the various body compartments and that, after fluid loading, the percentage of intravascular retention at the thoracic level is lower than that found in other studies (10-12). We found that the pulmonary permeability ratios were not related to the systemic ratios. Finally, we also explored a different method of optimisation of fluid in an attempt to predict the late response to fluid loading from the systemic permeability ratios.

Transpulmonary thermodilution is simple and quick, and can be done at the bedside although it has limitations (for example, in local pulmonary injury, extensive vascular obstruction and significant alteration of permeability). Despite these limitations, transpulmonary thermodilution measurements should be regarded as clinically useful indicators for assessing volumes and pulmonary permeability (6,7,31,32). With this procedure, we found that patients with septic shock had a lower proportion of fluids in the intrathoracic blood volume and more fluid in the interstitial compartments than the control group. This finding may reflect a reduction in the intravascular volume, although it could also have been influenced by intravascular redistribution towards the peripheral pool (28). We expected that increased pulmonary permeability would elevate the EVLWI in the septic group; however, although it was greater, it did not show a significant difference. These results are similar to those obtained by Marx (11), who accounted for them as the over-estimation of the EVLWI in healthy people. However, the results could also be due to the fact that in septic patients, the increase in extravascular pulmonary water is compensated for by an initial increase in lymphatic drainage (33). We cannot rule out the possibility that, in some pathologies, pulmonary and systemic permeability may vary in either intensity or time.

After fluid loading the septic group showed little capacity to retain fluid in the intravascular space. These patients experienced a much lower increase in ITBVI than the control group (10 vs 145 ml/[m.sup.2]), and they showed a decreased percentage of fluid retained in the ITBV (5.7% compared to 53% in the control group). These data are similar to those in the study of Marx et al, who added 300 ml of 20% albumin and measured the ITBVI at 90 minutes, finding that the group with alterations in permeability went from 775 [+ or -] 245 ml/[m.sup.2] to 761 [+ or -]216 ml/[m.sup.2] and that the control group went from 808 [+ or -] 397 ml/[m.sup.2] to 934 [+ or -] 392 ml/[m.sup.2] (11), but are different from the results obtained by Ernest et al, who found that large amounts of colloids were retained in the intravascular space, even during sepsis. However, in this particular study, 5% albumin, and not hydroxyethyl starch, was infused, different methods of measurement were employed and their focus was on the plasma volume without measuring the ITBVI (10). Recent studies conducted by Trof et al demonstrated a significant increase in both the ITBVI and cardiac output after administering colloids. The difference in results may be due to a less sick patient population in that study, with a lower Acute Physiology and Chronic Health Evaluation II score (14 [+ or -] 5) and much lower noradrenaline requirements (0.09 [micro]g/kg/minute). Moreover, in our study, a longer period of time had elapsed since the beginning of sepsis, and our resuscitation protocol might have been more restrictive after the first few hours, because we did not use CVP as a guide to fluid therapy, and we started early with vasoactive drugs. This difference may explain the lower basal ITBVI observed in our study (880 vs approximately 1100 ml/[m.sup.2] in the study by Trof et al (12)).

[FIGURE 1 OMITTED]

The slight increase of our patients' ITBVI levels might be due to more restrictive resuscitation, by which the PV values do not return to normal; however, the limited changes in the IDVGI and in the haemodilution, generated by the loading of fluid, seem to be more indicative of interstitial loss than of redistribution towards an intravascular peripheral pool. Many factors must be taken into account: the type of fluid employed, the protocol of resuscitation and a more or less aggressive use of inotrope and vasoactive drugs, the length of time that has elapsed from the beginning of the symptoms, the seriousness of the patient's condition, the method of measurement employed etc. Therefore, the difference in the results obtained is explainable and must be interpreted by considering the conditions in which said results were achieved.

We avoided techniques that included radioactive markers to measure plasma volume and we used indocyanine green, which binds to albumin, can be measured by pulse spectrophotometry and can be performed at the bedside in critically ill patients (34,35). One of the limitations of techniques that measure indocyanine green binding to albumin is overestimation of the blood volume. These errors occur because of the effusion of albumin from the intravascular space secondary to capillary leakage (18). However, as with other studies done with pulse densitometry, we did not find greater values in patients suspected of having alterations in vascular permeability (36). This result could be explained by the shorter time needed to complete the measurement, but we cannot rule out that the ability of the technique to discriminate may not always be enough.

The calculation of ECW was necessary but technically challenging. It required multiple blood measurements performed over 210 minutes. It did not offer results in real time and presented limitations as we could not obtain data starting from the elimination curve of sinistrin in three patients.

Just as in other studies (30), we used the ratios of the interstitial volumes to PVs as indicators of fluid redistribution and systemic permeability, and we found significant differences between both groups (P <0.04). The fundamental limitation of this ratio is that the interstitial volume does not depend only on the alteration of the permeability, but also on the amount of volume resuscitation and the time from the beginning of the alteration of the permeability. The systemic ratio was higher in the septic group than the control group, but it did not correlate with the pulmonary permeability ratio or with the blood volume retention percentage. This finding may mean that the alterations of pulmonary and systemic permeability are different, and in this case, transpulmonary thermodilution would be insufficient as a guide for fluid therapy in septic patients. However, it can also mean that these ratios are not comparable, in which case, we have several possibilities. The first is that the increase in interstitial volume is influenced by differences in tissue and lymphatic drainage. Second, the ITBVI is a measure of central intravascular volume and may be affected by resuscitation protocols, redistribution to the peripheral intravascular space, the pressures caused by mechanical ventilation and cardiorespiratory factors. In contrast, systemic ratios show more specifically the alteration of the permeability and thus could predict late responses to fluid. Therefore, perhaps we should distinguish initial responses to fluid that can be measured by transpulmonary thermodilution from delayed responses that are predicted using systemic indices. Although our study shows differences in the ratios between patients in the septic and control groups, it does not solve the problem of finding a reliable ratio which can be used at the bedside and which offers immediate results.

Finally, we measured the IDVG, a central volume that provides complementary data to the measurements of the classic compartments and which can serve as a non-invasive indicator of preload (16). This measurement is very simple and is repeatable over a short period of time. Ishihara (8) used the ratio of the PV to the IDVG as an indicator of capillary leakage. The index was elevated in septic patients because the measurement of PV was overestimated due to a protein leak. In our case, because we used a different methodology, we did not see these overestimations and the index was not useful as a detector of capillary leakage.

The limitations of this study are, first, that the controls had different reasons for admission, but for these pathologies there have not been published any significant changes regarding the distribution of fluids. Second, the number of patients in the study was too small. Third, we avoided more invasive techniques or having to relocate or move the patients, and therefore we did not always use gold standard measurements. However, the main results (increase of the ECW and the ITBVI) were performed with techniques that have been sufficiently acknowledged. Finally, in the septic group, the requirements for vasoactive drugs were very different, and this fact may imply a great difference in the severity and, therefore, in the degree of permeability alterations in this group.

In conclusion, septic shock can cause a redistribution of fluid. Fluid administration in these patients produced a minimal increase in intrathoracic blood volume and the percentage of volume retained in this space did not correlate with the systemic permeability ratio.

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M. SANCHEZ *, M. JIMENEZ-LENDINEZ *, M. CIDONCHA *, M. J. ASENSIO ([dagger]), E. HERRERO ([dagger]), A. COLLADO ([double dagger]), M. SANTACRUZ ([section])

Department of Intensive Care Medicine, University Hospital of La Paz, Madrid, Spain

* Ph.D, M.D., Intensive Care Specialist.

([dagger]) M.D., Intensive Care Specialist.

([double dagger]) M.D., Biochemistry Specialist.

([section]) Ph.D, M.D., Biochemistry Specialist.

Address for correspondence: Dr M. Sanchez, Hospital Universitario La Paz, Paseo de la Castellana 261. 28046, Madrid, Spain. Email: manuelsanchezsa@gmail.com

Accepted for publication on June 28, 2011.
Table 1
Clinical characteristics and laboratory data of patients with and
without septic shock

 Septic shock, n=18

Age, y 53 (39-67)
Gender, M/F 7/11
APACHE II score 16 (13-23)
Reasons for admission
 Respiratory 6 (pneumonia)
 Abdominal 7 (5 abdominal septic
 shock and 2 pancreatitis)
 Urology 3
 Neurosurgical 0
 Burns 2
 Drug intoxication 0
Haematocrit, % 33.0 (31.5-34.5)
Leukocytes, x [10.sup.9]/l 13.5 (4.8-25.2)
Total protein, g/l 48 (42-50)
C-reactive protein, mg/l 1160 (990-2600)
Heart rate, bpm 105 (66-121)
Mean arterial pressure, mmHg 69 (55-87)
Noradrenaline, [micro]g/kg/min 0.4 [+ or -] 0.4
Cardiac index, 1/min/[m.sup.2] 4.2 (2.7-4.7)
CVP, mmHg 8 (1-10)
[P.sub.a][O.sub.2]/Fi[O.sub.2], mmHg 255 (110-321)
Tidal volume, ml/kg 6.1 (5.1-6.9)
Mean peak inspiratory pressure, 29 (24-43)
 cm[H.sub.2]O
Volume expansion, ml 518 (455-581), (n = 11)

 Control, n=14 P values

Age, y 48 (25-71) NS
Gender, M/F 6/8 NS
APACHE II score 16 (14-24) NS
Reasons for admission
 Respiratory 5 (asthma, COPD)
 Abdominal 0

 Urology 0
 Neurosurgical 7
 Burns 0
 Drug intoxication 2
Haematocrit, % 35.0 (30.1-38.0) NS
Leukocytes, x [10.sup.9]/l 11.9 (4.9-15.3) NS
Total protein, g/l 59 (52-63) <0.001
C-reactive protein, mg/l 650 (190-850) <0.01
Heart rate, bpm 87 (62-98) NS
Mean arterial pressure, mmHg 76 (70-98) NS
Noradrenaline, [micro]g/kg/min
Cardiac index, 1/min/[m.sup.2] 3.4 (2.8-3.8) NS
CVP, mmHg 10 (4-15) NS
[P.sub.a][O.sub.2]/Fi[O.sub.2], mmHg 260 (122-420) NS
Tidal volume, ml/kg 6.4 (5.3-7.2) NS
Mean peak inspiratory pressure, 27 (21-36) NS
 cm[H.sub.2]O
Volume expansion, ml 512 (455-546), NS
 (n = 11)

Median (quartile range). NS=non-significant, M=male, F=female,
APACHE=Acute Physiology and Chronic Health Evaluation, COPD=chronic
obstructive pulmonary disease, CVP=central venous pressure.

Table 2
Measurements of transpulmonary dilution and systemic volumes

 Septic shock, Control, P values
 n=18 n=14

ITBVI, ml/[m.sup.2] 894 (766-990) 1157 (957-1321) <0.003
EVLWI, ml/kg 9 (6-17) 8 (7-9) NS
PBVI, ml/kg 4.4 (3.8-4.9) 5.7 (4.6-6.6) 0.002
CBVI, ml/kg 53 (45-64) 60 (52-65) NS
PVI, ml/kg 36 (30-45) 40 (31-44) NS
ECWI, ml/kg 295 (254-320) * 234 (211-244) <0.001
IDVGI, ml/kg 129 (112-141) 137 (129-137) NS

Median (quartile range). ITBVI=intrathoracic blood volume index,
EVLWI=extravascular lung water index, NS=non-significant,
PBVI=pulmonary blood volume index, CBVI=circulating blood
volume index, PVI=plasma volume index, ECWI=extracellular
water index, IDVGI=initial distribution volume of glucose index.

* n=15.

Table 3
Ratios between compartments

 Septic shock, Controls,
 n=18 n=15

EVLW/PBV 1.85 (1.56-2.85) 1.32 (1.12-1.63)
PV/IDVG 0.29 (0.22-0.34) 0.30 (0.26-0.33)
Interstitial/PV 7.9 (5.9-9.9) * 5.6 (3.9-6.6)
ITBV-Rp 4 (0-34) ([dagger]) 55 (45-64) ([dagger])

 P values

EVLW/PBV 0.003
PV/IDVG NS
Interstitial/PV 0.04
ITBV-Rp 0.003

Median (quartile range). EVLW=extravascular lung water,
PBV=pulmonary blood volume, PV=plasma volume,
IDVG=initial distribution volume of glucose, NS=non-significant,
ITBV=intrathoracic blood volume, ITBV-Rp=intrathoracic blood
volume retention percentage. * n = 15. ([dagger]) n = 11.
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Author:Sanchez, M.; Jimenez-Lendinez, M.; Cidoncha, M.; Asensio, M.J.; Herrero, E.; Collado, A.; Santacruz,
Publication:Anaesthesia and Intensive Care
Article Type:Clinical report
Date:Nov 1, 2011
Words:5559
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