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Goal-Directed Fluid Management by Bedside Transpulmonary Hemodynamic 

Monitoring After Subarachnoid Hemorrhage 

Tatsushi Mutoh, Ken Kazumata, Minoru Ajiki, Satoshi Ushikoshi and Shunsuke 

Terasaka 

Stroke published online Nov 8, 2007; 

DOI: 10.1161/STROKEAHA.107.484634 

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Goal-Directed Fluid Management by Bedside 

Transpulmonary Hemodynamic Monitoring 

After Subarachnoid Hemorrhage 

Tatsushi Mutoh, MD, DVM, PhD; Ken Kazumata, MD; Minoru Ajiki, MD; 

Satoshi Ushikoshi, MD; Shunsuke Terasaka, MD 

Background and Purpose—Optimal monitoring of cardiac output and intravascular volume is of paramount importance 

for good fluid management of patients with subarachnoid hemorrhage (SAH). The aim of this study was to demonstrate 

the feasibility of advanced hemodynamic monitoring with transpulmonary thermodilution and to provide descriptive 

data early after SAH. 

Methods—Forty-six patients with SAH treated within 24 hours of the ictus were investigated. Specific targets for cardiac 

index (�3.0 L � min �1 � m �2 ), global end-diastolic volume index (700 to 900 mL/m 2 ), and extravascular lung water index 

(�14 mL/kg) were established by the single-indicator transpulmonary thermodilution technique, and a fluid 

management protocol emphasizing supplemental colloid administration was used to attain these targets. Plasma 

hormones related to stress and fluid regulation were also measured. 

Results—A higher cardiac index (mean value of 5.3 L � min �1 � m �2 ) and a lower global end-diastolic volume index (555 

mL/m 2 ) were observed on initial measurement, for which elevations of plasma adrenaline, noradrenaline, and cortisol 

were also detected. Cardiac index was progressively decreased (3.5 L � min �1 � m �2 ) and global end-diastolic volume 

index was normalized by fluid administration aimed at normovolemia. The extent of the initial hemodynamic and 

hormonal profile was greater in patients with a poor clinical status (P�0.05). The extravascular lung water index was 

mildly elevated but within the target range throughout the study period. No patients developed pulmonary edema or 

congestive heart failure. 

Conclusions—The impact of sympathetic hyperactivity after SAH predisposes patients to a hyperdynamic and 

hypovolemic state, especially in those whose clinical status is poor. Bedside monitoring with the transpulmonary 

thermodilution system may be a powerful tool for the systemic management of such patients. (Stroke. 

2007;38:000-000.) 

Key Words: hemodynamic monitoring � stress � subarachnoid hemorrhage � transpulmonary thermodilution 

Aneurysmal subarachnoid hemorrhage (SAH) is one of 

the most striking and devastating neurologic disorders. 

SAH affects most central nervous system functions, leading 

to deleterious systemic consequences. It is recognized that 

SAH is associated with a “catecholamine surge” due to 

hypothalamic and brainstem activation. 1 Neurocardiogenic 

injuries, such as neurogenic stunned myocardium and neurogenic 

pulmonary edema, are thought to result from exaggerated 

sympathetic tone and elevated circulating levels of 

catecholamines at the site of aneurysm rupture. 2,3 Hypovolemia 

accompanied by cerebral salt wasting and a progressive 

reduction of extracellular fluid volume also occurs frequently 

within a few days after symptom onset, possibly through 

central nervous system–mediated mechanisms. 4,5 

Brain regions with marginal perfusion and loss of autoregulation, 

hypotension, and hypovolemia, all of which can 

exacerbate decreases or reductions in cerebral blood flow, 

have been shown to increase the incidence of cerebral 

vasospasm and the related delayed ischemic neurologic deficits 

resulting from the earlier detrimental effects on blood 

pressure and cardiac output (CO). In this context, hypervolemia, 

hypertension, and hemodilution therapy is believed to 

prevent ischemic events and improve outcome and is central 

to the medical management of symptomatic vasospasm. 6 

To ensure appropriate intravascular volume and CO for 

good fluid management in patients after SAH, an optimal 

hemodynamic monitoring technique is of paramount importance. 

However, no bedside monitoring system has been 

practicable for estimating both CO and volume status simultaneously, 

other than the pulmonary artery catheter in the 

intensive care unit setting. Moreover, few studies concerning 

the serial changes in cardiac performance and circulating 

Received April 18, 2007; accepted May 4, 2007. 

From the Department of Neurosurgery, Teine Keijinkai Medical Center, Sapporo, Japan. 

Correspondence to Tatsushi Mutoh, MD, DVM, PhD, Department of Strokology, Research Institute of Brain and Blood Vessels, Akita, 6-10 

Senshu-Kubota-machi, Akita 010-0874, Japan. E-mail tmutoh@tiara.ocn.ne.jp 

© 2007 American Heart Association, Inc. 

Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.107.484634 


stroke.ahajournals.org 1 by guest on November 16, 2007

2 Stroke December 2007 

blood volume early after the insult of SAH, which may 

predispose these patients to volumetric and hemodynamic 

impairments, have been documented. 

The single thermal indicator transpulmonary dilution system 

is a device for continuous CO measurement combined 

with cardiac preload volume and extravascular lung water 

(EVLW) monitoring. It computes CO with an arterial pulsecontour 

analysis algorithm after calibration by means of the 

transpulmonary thermodilution method to measure the volumetric 

preload parameter that includes the total volumes of 

the cardiac atria and ventricles, as well as part of the systemic 

vascular blood volume. Bedside monitoring with this system 

offers the facility to measure CO with only central venous and 

arterial catheters; it has numerous clinical advantages in 

patients with hemodynamic instability or critical illness in 

whom continuous measurement of CO is required, and it 

avoids the well-documented risks associated with the use of 

the pulmonary artery catheter. 7 

We hypothesized that compared with conventional 

pressure-derived preload assessment, volumetric preload determination 

by the transpulmonary thermodilution system 

would better reflect left ventricular filling, thereby giving a 

better estimate of the safety and efficacy of volume therapy to 

minimize associated cardiopulmonary complications, such as 

pulmonary edema or congestive heart failure. Hence, the aim 

of this study was to investigate the serial changes in cardiac 

performance and volume status in patients with SAH treated 

postoperatively with normovolemia guided by the transpulmonary 

thermodilution technique. The mechanism of change 

in CO and circulating blood volume early after SAH was 

examined by measuring hormones related to stress and fluid 

regulation. 

Methods 

Patients 

Forty-six consecutive patients (14 men and 32 women; mean�SD 

age, 65�11 years) with aneurysmal SAH were investigated in the 

Department of Neurosurgery, Teine Keijinkai Medical Center. The 

study protocol was approved by the institutional ethics committee, 

and informed consent was obtained from each patient or appropriate 

designee. Patients entered the study on the day after surgical clipping 

or intravascular coiling for aneurysm within 24 hours of the onset of 

symptoms (designated study day 0). Exclusion criteria included the 

following conditions: (1) both good clinical grade (World Federation 

of Neurological Surgery [WFNS] grade I) and modest bleeds (Fisher 

CT grade �2); (2) renal disease (creatinine level �2.0 mg/dL); or (3) 

death within 7 days of bleeding. Fifty-six patients were screened, of 

whom 46 met the inclusion criteria and were enrolled between April 

2005 and October 2006. Neurologic outcome was assessed by the 

modified Rankin scale score for all patients after 1 month. A 

summary of clinical data is given in the Table. 

Experimental Procedures 

General Management 

All patients had a 7F central venous catheter inserted into the femoral 

vein postoperatively and received a baseline infusion of crystalloid 

(1500 to 3000 mL/d) for up to 14 days after onset of SAH. The 

patients were maintained on bed rest with intravenous fluids and oral 

food intake if possible. Intracranial hypertension was treated with 

glycerol and/or cerebrospinal drainage. Hyponatremia (defined as a 

serum sodium level of �135 mEq/L for at least 2 consecutive days) 

was corrected by adding an ampule(s) of 10% NaCl (20 mL) to the 

main fluid bag. If hyponatremia persisted, fludrocortisone (0.3 mg/d) 

Table. Clinical Characteristics of 46 Patients With SAH 

Characteristics No. of Patients 

Sex, M/F 14/32 

Age, y 

�49 2 

50–59 15 

60–69 11 

70� 18 

WFNS grade 

I 12 

II 9 

III 2 

IV 14 

V 9 

Fisher CT grade 

3 32 

4 14 

Aneurysm location 

ACoA/ACA 15 

MCA 13 

ICA 12 

Other 6 

Treatment 

Aneurysmal clipping/coiling 31/15 

Outcome at 1 month, mRS score 

0 6 

1 6 

2 8 

3 7 

4 11 

5 6 

6 2 

mRS indicates modified Rankin Scale; ACA, anterior cerebral artery; AcoA, 

anterior communicating artery; MCA, middle cerebral artery; and ICA, internal 

carotid artery. 

or hydrocortisone (1200 mg/d) was given as necessary. 8 Blood 

transfusion was performed only when the hematocrit level was 

�30%. If the maximal systolic blood pressure was �200 mm Hg, a 

calcium antagonist was administered. Nimodipine was not used (this 

drug is unavailable in Japan). 

Patients were followed up by transcranial Doppler sonography 

daily or every other day according to the standard criteria for 

angiographic vasospasm. 9 Delayed ischemic neurologic deficit was 

defined as a worsening of the neurologic condition that could not be 

attributed to rebleeding or systemic or postoperative complications. 

Surveillance angiography was performed when patients did not 

respond to medical treatment. When the caliber of any artery was 

�50% of that observed on the admission angiogram, ischemia due to 

cerebral vasospasm was diagnosed. 10 

Single-Indicator Transpulmonary Thermodilution 

A 4F thermistor-tipped arterial catheter (PV2014L16, Pulsion Medical 

Systems, Munich, Germany) was inserted into the brachial 

artery. The arterial catheter and a central venous catheter were 

connected to pressure transducers and to the single thermal indicator 

dilution system (PiCCO, Pulsion Medical Systems) for monitoring. 

Continuous CO calibration, global end-diastolic volume (GEDV), 



and EVLW were determined by triplicate central venous injections 

of 15 mL of ice-cold saline (�8°C). CO was calculated by analysis 

of the thermodilution curve followed by pulse-contour analysis for 

continuous monitoring. GEDV was calculated from the difference of 

mean indicator transit time and exponential indicator downslope 

time and from CO. EVLW was calculated from GEDV based on a 

fixed algorithm established from data obtained from earlier doubleindicator 

transpulmonary thermodilution. The basis of this method 

can be accessed in the supplemental material, available online at 

http://stroke.ahajournals.org. 

Hemodynamic values were indexed to body surface area by means 

of the DuBois formula: body weight (in kilograms)�body length (in 

centimeters) 0.725 �1.84. In this study, cardiac index (CI), GEDV 

index (GEDVI), and EVLW index (EVLWI) were calculated. 

Measurements 

The following measurements were performed during the postoperative 

period (days 1 to 14) after the onset of SAH: CI (normal values, 

3.0 to 5.0 L � min �1 � m �2 ), GEDVI (680 to 800 mL/m 2 ), EVLWI 

(3 to 7 mL/kg), central venous pressure (CVP), plasma adrenaline, 

noradrenaline, cortisol, aldosterone, antidiuretic hormone (ADH), 

and brain natriuretic peptide (BNP). Water balance was calculated 

from the difference between the total amount of water intake (sum of 

transvenously infused water and orally ingested water) and water 

losses (sum of urine, transpirated water, and various drainage fluids). 

Metabolized water and water included in the stool were not included 

in this study. 

The CI, GEDVI, EVLWI, and CVP were measured at least twice 

daily until day 14; plasma adrenaline, noradrenaline, cortisol, ADH, 

and BNP were measured initially on admission, at 12 hours, and 

daily until day 3 by commercially available radioimmunoassay; and 

other blood and chemical parameters were measured daily or every 

other day until day 14 by automatic analyzer. Water balance was 

measured every 8 hours until day 14. 

PiCCO-Guided Fluid Management 

Basic fluid management was aimed at the maintenance of CO, which 

was our primary method to increase cerebral blood flow medically, 

and prevention of hypovolemia and cardiopulmonary complications. 

6,11 Hemodynamic stability was defined as a CI �3.0 

L � min �1 � m �2 , a GEDVI �700 mL/m 2 (lower limits were defined at 

lower values as the normal 680 to 800 mL/m 2 ), and EVLWI �14 

mL/kg (upper limits were defined at a higher risk of mortality with 

pulmonary edema when EVLW �14 mL/kg.). 12 Patients were 

assigned to receive intravascular volume expansion with 6% hydroxyethylstarch 

(500 to 1500 mL/d) if CI fell below the target level 

(�3.0 L � min �1 � m �2 ) due to hypovolemia (GEDVI �700 mL/m 2 ). 

When hydroxyethylstarch was ineffective in raising GEDVI above 

the lower target values and low CI persisted for at least 24 hours, 

supplemental 25% albumin solution (50 to 100 mL/d) was administered. 

If the low CI persisted even under hypervolemia (GEDVI 

�900 mL/m 2 , EVLWI �14 mL/kg) along with fluid therapy for at 

least 24 hours, inotropic support with dobutamine (3 to 15 

�g � kg �1 � min �1 ) or milrinone (0.25 to 0.75 �g � kg �1 � min �1 ) 13 was 

started to maintain the CI above target levels. When the patient had 

an elevated EVLWI (�15 mL/kg) and any sign of congestive heart 

failure or pulmonary edema (eg, bilateral pulmonary infiltrates 

and/or cardiomegaly observed with a cardiothoracic ratio �50% on 

chest radiography), furosemide (5 to 20 mg/d) was administered until 

EVLWI was reduced to �14 mL/kg. This fluid management protocol 

was strictly adhered to throughout the entire study period unless 

symptomatic vasospasm was diagnosed. 

Patients who become symptomatic with delayed ischemic neurologic 

defect due to vasospasm were managed by enhancement of 

their cardiac contractility (“hyperdynamic therapy”) 14 by the use of 

inotropes to titrate the CI above normal limits (�5.0 L � min �1 � m �2 ) 

to the level at which the deficit resolved or until a maximal systolic 

blood pressure of 200 mm Hg was achieved. 

Mutoh et al Bedside Hemodynamic Monitoring After SAH 3 

Statistical Analysis 

All data were stored on a personal computer and analyzed by 

commercially available software (SPSS version 15.0, SPSS Inc, 

Chicago, Ill). Data that were collected sequentially with a data 

acquisition system (PiCCO-VoLEF-Win version 6.0, Pulsion Medical 

Systems) were examined by repeated-measures ANOVA with a 

post hoc Bonferroni-Dunn correction or paired t test. Categorical 

data were analyzed by � 2 test. Comparisons between groups were 

examined with an unpaired t test when the dispersions of the 2 

groups were equal or by the Mann-Whitney U test. The Pearson 

correlation was established for absolute values between stress 

hormones and CI. Statistical significance was claimed when the 

probability of a type I error was �0.05. All values were expressed as 

mean�SD. 

Results 

Stress Response and Hemodynamic Outcomes 

After SAH 

The time-course changes of CI, GEDVI, and EVLWI obtained 

from the single-indicator transpulmonary thermodilution 

technique in 46 patients after SAH and early surgery are 

shown in Figure 1. High CI values (5.3�0.4 L � min�1 � m�2 ) 

were detected on day 1, which progressively fell to a 

minimum of 3.5�0.2 L � min�1 � m�2 on day 5 (P�0.05). 

Conversely, the GEDVI was low (555�27 mL/m2 ) on day 1 

but normalized to 740�47 mL/m2 (P�0.05) by day 3 by 

titrating fluid administration aimed at normovolemia. 

Throughout the study period, EVLWI remained slightly 

raised (10.4�2.3 mL/kg). 

Initial plasma noradrenaline concentrations sampled on 

admission were 1.6 times higher (0.79�0.15 ng/mL) than the 

reference level but then returned to close to the upper normal 

limits (0.39�0.05 ng/mL) after 24 hours. Plasma adrenaline 

concentrations were mildly elevated (0.11�0.02 ng/mL) on 

admission but also returned to within the normal range after 

24 hours. Plasma cortisol was also high (24.8�2.0 �g/dL) on 

admission but gradually returned to the normal range within 

48 hours. There were no statistically significant time-course 

changes in plasma aldosterone, ADH, and BNP throughout 

the study period (P�0.05). Linear-regression analysis between 

the stress hormones and CI showed significant correlations 

for adrenaline (r2�0.390, P�0.0001), noradrenaline 

(r2�0.453, P�0.0001), and cortisol (r2�0.388, P�0.0001; 

Figure 2). 

Comparison of Hemodynamic Outcomes Between 

Good and Poor Grades 

Initial measurements after SAH without the effect of fluid 

regulation were compared between clinical grades (WFNS 

grades I–III versus grades IV and V; Figure 3). Higher CI and 

plasma concentrations of adrenaline (0.06�0.02 versus 

0.13�0.02 ng/mL), noradrenaline (0.46�0.10 versus 

1.06�0.25 ng/mL), and cortisol (21.8�2.4 versus 29.1�3.0 

�g/dL) and lower GEDVI values were present in SAH 

patients with a poor clinical grade (P�0.05 for each). 

Although in patients with a poor clinical grade the EVLWI 

values tended to be higher, the difference was not statistically 

significant (P�0.07). There were no statistically significant 

differences in plasma aldosterone, ADH, and BNP between 

good and poor grades (P�0.05). 




A 

CI (L/min/m 2 ) 

B 

GEDVI (mL/m 2 ) 

C 

EVLWI (mL/kg) 

5.5 

4.5 

3.5 

2.5 

1000 

800 

600 

400 

20 

15 

10 

5 

0 

1 2 3 4 5 6 7 8 9 10 11 12 13 14 

1 2 3 4 5 6 7 8 9 10 11 12 13 14 

1 2 3 4 5 6 7 8 9 10 11 12 13 14 

Day after SAH onset 

Figure 1. Time-course changes of CI, GEDVI, and EVLWI for 14 

days in 46 patients after SAH. Lower hatched box on the vertical 

axis indicates the normal range of each variable. 

Overall Performance of Transpulmonary 

Thermodilution System 

In 43 patients (93%), the hemodynamic targets (CI �3.0 

L � min �1 � m �2 , GEDVI �700 mL/m 2 , and EVLWI �14 

mL/kg) were obtained by using the fluid management protocol 

until day 3�2 (mean�SD; range, 1 to 8) after SAH onset. 

However, 3 patients failed to reach the established target 

values. In all cases CI and EVLWI were within the target 

range, but a low GEDVI (�700 mL/m 2 ) persisted throughout 

the study period. 

For fluid management, 4 patients (9%) were given maintenance 

fluid infusion only and oral intake; 38 patients (83%) 

were administered supplemental hydroxyethylstarch for volume 

expansion; and 26 patients (57%) were given 25% 

Figure 2. Correlation coefficients between stress hormones and 

CI in 46 patients after SAH. Hormonal data were sampled on 

admission, and CI was obtained immediately after application of 

the transpulmonary thermodilution system. 



CI (L/min/m 2 ) 

A B C 

* * 

6 

5 

4 

3 

I-III IV,V 

GEDVI (mL/m 2 ) 

1100 

900 

700 

500 

I-III IV,V 

albumin. To obtain a CI �3.0 L � min �1 � m �2 , 3 patients (7%) 

required inotropic support with dobutamine (4%, n�2) or 

milrinone (2%, n�1). Hyponatremia developed in 24 patients 

(52%; n�10 in grades I–III and n�14 in grades IV and V); 

in most, their condition was corrected by adding 10% NaCl to 

the main fluid, 2 patients needed oral fludrocortisone, and 3 

required intravenous hydrocortisone. For the correction of 

anemia (hematocrit �30%), 11 patients (24%) required blood 

transfusion. Furosemide (10 mg/d for 3 days) was used in 1 

patient to treat an elevated EVLWI due to neurogenic 

pulmonary edema. 

The daily fluid intake of all patients was gradually increased 

(eg, 2661�547 mL/d; range, 1516 to 3807 mL/d until 

day 3 and 4336�907 mL/d; range, 2324 to 5959 mL/d after 

day 4; n�46), and patients with a poor clinical grade required 

significantly greater fluid administration on day 5 (P�0.05; 

Figure 4). Net daily fluid balance and CVP were not significantly 

different throughout the study period nor between 

clinical grades (P�0.05). 

Of the 17 patients (37%) who met the standard criteria for 

angiographic vasospasm, 9 (20%) remained asymptomatic, 

whereas 8 (17%) showed a delayed ischemic neurologic 

defect and had direct angiographic verification of vasospasm. 

Patients who experienced symptomatic neurologic deterioration 

due to vasospasm were switched to hyperdynamic 

therapy with dobutamine during the study. At the onset of 

symptomatic vasospasm (9�2 days; range, 6 to 12 days after 

SAH onset), the CI was 3.3�0.3 L � min �1 � m �2 (within the 

lower limit of normal), and all of them were started on 

dobutamine at a maximum mean�SD dose of 6.7�2.4 

�g � kg �1 � min �1 (range, 3 to 12 �g � kg �1 � min �1 ) to attain a 

CI of 5.1�0.6 L � min �1 � m �2 until 10�2 days (range, 7 to 13 

days) after SAH onset. Cerebral infarctions secondary to a 

vasospasm-induced delayed ischemic neurologic defect occurred 

in 4 patients (9%). 

In this study, no patient developed pulmonary edema or 

congestive heart failure during fluid therapy, except for the 

presence of neurogenic pulmonary edema in 4 patients (9%) 

and neurogenic stunned myocardium (“Tako-tsubo” cardiomyopathy) 

in 1 patient (2%) diagnosed on admission. 

Discussion 

This study provides new evidence for ongoing hemodynamic 

monitoring of cardiac performance and volume status with 


EVLWI (mL/kg) 

15 

10 

5 

0 

I-III IV,V 

Figure 3. Comparison of CI, GEDVI, and 

EVLWI between SAH patients with a 

good (WFNS grades I–III; n�23) and a 

poor (grades IV and V; n�23) clinical 

grade. These hemodynamic variables 

were obtained immediately after application 

of the transpulmonary thermodilution 

system.*P�0.05 vs grades I–III. 

the single-indicator transpulmonary thermodilution technique. 

We have demonstrated that CO increases progressively 

and significantly early after SAH, which was strongly associated 

with stress-induced sympathetic hyperactivity at the 

site of aneurysmal rupture, especially in patients with a poor 

clinical grade. Bedside monitoring with the single-indicator 

transpulmonary thermodilution system may be a powerful 

tool for systemic management. 

An incremental relation was observed between the WFNS 

grade, which is widely used in assessing the severity of 

neurologic injury after SAH, and the hyperdynamic/hypovolemic 

state early after SAH. It is known that the release of 

norepinephrine induces peripheral and splanchnic vasoconstriction, 

a major contributor to the maintenance of central 

organ perfusion, whereas reduced vagal activity increases 

heart rate and CO. Our finding is consistent with previous 

studies 15,16 that showed that patients with more severe grades 

of SAH had a higher incidence of catecholamine release, as 

estimated by an increased stress index obtained from a 

combination of blood sugar level/serum potassium concentration 

or by direct measurement of plasma catecholamine 

levels. Those investigations demonstrated that the plasma 

catecholamine level was extremely high in the superacute 

stage (within an hour of bleeding) but decreased fairly 

quickly at 24 hours to the normal range. Given the higher 

correlation and similar time-course changes observed between 

the stress hormones (epinephrine, norepinephrine, and 

cortisol) and CI, acute stress caused by SAH can contribute to 

the sympathetic hyperactivation that induces a hyperdynamic 

state at an early stage, depending largely on the intensity of 

the initial stress. Adverse physical (eg, burn trauma, infection, 

or sepsis) and psychological conditions can activate the 

sympathetic nervous system, the hypothalamic-pituitaryadrenal 

axis, immune cells, and cytokines, which can initiate 

the stress-response cascade 16–18 that regulates myocardial and 

adrenal transcription/translation genes 19,20 and culminates in 

cardiac contraction/relaxation defects or an impairment of 

fluid/sodium retention. Such actions and others may negatively 

affect the heart in several ways. 

Natriuresis was reported to be 1 of the major factors of 

volume contraction several days after SAH. 21 Most patients 

who demonstrated hyponatremia showed a decrease in 

plasma volume by �10% 22 or failed to maintain CVP within 




A 

Fluid Intake-Output (mL/d) 

B 

Fluid Balance (mL/d) 

C 

CVP (cmH 2 O) 

5000 

4000 

3000 

2000 

1000 

0 

-1000 

-2000 

-3000 

-4000 

-5000 

1 2 3 4 5 6 7 8 9 1011121314 

+1500 Grade I-III 

Grade IV,V 

+1000 

+500 

±0 

-500 

-1000 

-1500 

16 Grade I-III 

Grade IV,V 

14 

12 

10 

8 

6 

4 

2 

0 

* 

* 

1 2 3 4 5 6 7 8 9 10 11 12 13 14 

1 2 3 4 5 6 7 8 9 1011121314 

Day after SAH onset 

Grade I-III 

Grade IV,V 

Figure 4. Daily fluid intake/output, fluid balance, and CVP 

changes for 14 days in SAH patients with a good (WFNS grades 

I–III, n�23; shown in white bars/circles) and a poor (grades IV 

and V, n�23; shown in black bars/circles) clinical grade. 

*P�0.05 vs grades I–III. 

the target range (8 to 12 cm H 2O), 8 suggesting the presence 

of hypovolemia, consistent with the cerebral salt-wasting 

syndrome. However, we did not find any correlations 

between a decrease in GEDVI and hormonal changes, such 

as mineralocorticoid deficiency or an excessive release of 

BNP. The reduction in GEDVI after SAH may not be a 

simple phenomenon that can be explained by a single 

hormonal change. A reduction in circulating blood volume 

after stress is caused by the shift of fluid to the interstitial 

spaces, which may in part explain the initial depression of 

GEDVI and the need for optimizing hemodynamics early 

after SAH. 

Patients with pulmonary complications after SAH are more 

prone to vasospasm and are at higher risk for mortality and 

neurogenic morbidity. Furthermore, patients who are subjected 

to administration of large amounts of fluid as well as 

vasopressors to maintain a higher CO associated with hypervolemia, 

hypertension, and hemodilution therapy may have a 

higher risk of pulmonary edema. 6 The transpulmonary thermodilution 

system has been shown to quantify EVLW with a 

very high correlation to conventional gravimetric measurement 

of EVLW, 23 which allowed us to minimize pulmonary 

edema and/or congestive heart failure by directing adequate 

volume status after SAH. In the present study, the decreased 

intravascular volume that developed at an early stage, largely 

in patients with a poor clinical grade, was able to establish 

hemodynamic stability safely and appropriately before the 

onset of cerebral vasospasm without overloading, according 

to the protocol for this method. 

Good fluid management of cerebral vasospasm involves 

knowing how much hydration patients will tolerate before 

developing complications such as pulmonary edema and 

congestive heart failure due to fluid overloading. Serial 

volume measurements as estimated by GEDVI and EVLWI 

with the transpulmonary thermodilution method proved to be 

sufficiently practical and accurate and would be useful for 

monitoring patients after SAH. The system also allows 

continuous assessment of CO, which gave us the opportunity 

to respond rapidly to hemodynamic changes. So far, this 

system has not been validated in patients with SAH except for 

a case report, wherein the catheters was placed a few days 

after the occurrence of vasospasm. 24 Although this study 

included a small number of patients, we believe that our 

initial experience with SAH patients indicates a potentially 

effective monitoring technique for the management of cerebral 

vasospasm. Future studies should continue to focus on 

safety and better definition of the optimal protocol and 

overall efficacy of this therapy. 

Our study has shown that this methodology is useful and 

can be applied repeatedly for estimating cardiac performance 

and the volume status of neurosurgical patients with a bolus 

injection of cold saline solution. A recent randomized, controlled 

trial of CVP–guided volume expansion also failed to 

demonstrate an increase in circulating blood volume in 

patients after SAH or sepsis. 4 Cardiac filling pressures also 

afforded a poor prediction of fluid responsiveness after the 

early phase of sepsis. 25,26 Although a comparison between the 

transpulmonary thermodilution technique and conventional 

monitoring to guide fluid therapy in SAH patients has not 

been performed and should be confirmed in the future, the 

finding that neither net fluid balance nor CVP changed 

significantly throughout the study period (Figure 4) may 

support the concept that theses parameters are poor predictors 

of volume expansion. In fact, several studies have demonstrated 

that volumetric cardiac preload measurements assessed 

by transpulmonary thermodilution better reflect left 

ventricular filling than pulmonary artery catheter–derived 



pulmonary artery occlusion pressure to estimate left ventricular 

end-diastolic volume, 27,28 indicating the superiority of 

volumetric monitoring of cardiovascular volume status over 

conventional pressure monitoring. 

Acknowledgments 

We are grateful to the entire nursing staff of the Teine Keijinkai 

Medical Center Neurosurgical Intensive Care Unit for their kind and 

generous help, without which this work could not have 

been completed. 

None. 

Disclosures 

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Supplemental Material 

Single-Indicator Transpulmonary Thermodilution 

The single-indicator transpulmonary thermodilution system 

measures the change in temperature over time induced by a 

bolus injection of cold saline (supplemental Figure I, available 

online at http://stroke.ahajournals.org). CO is then calculated 

by analysis of the thermodilution curve according to 

the Stewart-Hamilton equations. 1 The measurement of CO by 

transpulmonary thermodilution has been previously validated 

against pulmonary thermodilution and the Fick method. By 

using standard equations, the system calculates the flow (Q˙ ) 

and mean transit time (t�) for the thermal indicator. By 

multiplying these 2 factors, the system can determine the 

thermal distribution volume between the site of injection and 

the thermistor. This volume is denoted as intrathoracic 

thermal volume (ITTV�Q˙ �t�). Moreover, the system measures 

the downslope time of the logarithmically transformed 

dilution curve. By multiplying the downslope time by Q˙ , the 

system calculates the volume of the largest mixing chamber 

in the serial system comprising the chambers of the heart and 

the lungs, according to Newman et al. 2 The largest mixing 

chamber for the thermal indicator is denoted as pulmonary 

thermal volume (PTV�DSt�Q˙ ) and comprises pulmonary 

blood volume and lung tissue. By subtracting PTV from 

ITTV, the composite extrapulmonary blood volume between 

the site of injection and the thermistor can be calculated; this 




Figure I. Single-indicator transpulmonary thermodilution system. 

Schematic illustration of the transpulmonary thermodilution system 

(PiCCO) was modified with permission from Pulsion Medical 

Systems (Munich, Germany). 

is GEDV (GEDV�ITTV�PTV). To calculate EVLW 

(EVLW�ITTV�ITBV), intrathoracic blood volume (ITBV) 

must be determined so that the system can use the empirically 

established linear relation between intrathoracic volume and 

GEDV to calculate ITBV. 3 The default relation used by the 

PiCCO system, ITBV�1.25�GEDV, is based on a study by 

Sakka et al. 4 

The PiCCO system operates in such a way that every time 

a thermodilution injection is performed, the pulse contour 

analysis automatically and immediately self-calibrates from 

the shape of the arterial pressure wave with the new value 

from the transpulmonary thermodilution method to compute 

each single stroke volume (SV). 5 As pulse contour analysis 

continuously measures SV and arterial pressure, CO 

(CO�SV�heart rate) and systemic vascular resistance (mean 

arterial pressure�CVP/CO) are computed simultaneously 

and displayed for continuous monitoring. 

Supplemental References 

1. Profant M, Vyska K, Eckhardt U. The Stewart-Hamilton equations and the 

indicator dilution method. SIAM J Appl Math. 1978;34:666–675. 

2. Newman EV, Merrell M, Genecin A, Monge C, Milnor WR, McKeever 

WP. The dye dilution method for describing the central circulation: an 

analysis of factors shaping the time-concentration curves. Circulation. 

1951;4:735–746. 

3. Kirov MY, Kuzkov VV, Bjertnaes LJ. Extravascular lung water in sepsis. 

In: Vincent JL, ed. Yearbook of Intensive Care and Emergency Medicine. 

Berlin: Springer-Verlag; 2005:449–461. 

4. Sakka SG, Ruhl CC, Pfeiffer UJ. Assessment of cardiac preload and 

extravascular lung water by single transpulmonary thermodilution. 

Intensive Care Med. 2000;26:180–187. 

5. Gödje O, Hoke K, Goetz AE, Felbinger TW, Reuter DA, Reichart B, Friedl 

R, Hannekum A, Pfeiffer UJ. Reliability of a new algorithm for continuous 

cardiac output determination by pulse-contour analysis during hemodynamic 

instability. Crit Care Med. 2002;30:52–58.

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