Effects of hypertonic 75 mg/ml

Acta Anaesthesiol Scand 2001; 45: 776–781
Printed in Denmark. All rights reserved
Copyright C Acta Anaesthesiol Scand 2001
ACTA ANAESTHESIOLOGICA SCANDINAVICA
ISSN 0001-5172
Effects of hypertonic 75 mg/ml (7.5%) saline on extracellular
water volume when used for preloading before spinal
anaesthesia
K. JÄRVELÄ1, T. KÖÖBI2, P. KAUPPINEN3 and S. KAUKINEN1
Departments of 1Anaesthesia and Intensive Care and 2Clinical Physiology, Tampere University Hospital, Tampere and 3Ragnar Granit Institute, Tampere
University of Technology, Tampere, Finland
Background: Prevention of hypotension during spinal anaesthesia is commonly achieved using fluid preloading. This may
result in a substantial amount of excess free water retained in
the body after spinal anaesthesia. We aimed to evaluate the effects of 7.5% hypertonic saline on extracellular water volume
and haemodynamics when used for fluid preloading before
spinal anaesthesia.
Methods: This randomised double-blind study evaluated the
effects of 75 mg/ml (7.5%) hypertonic saline (HS) on extracellular water volume and haematocrit in patients undergoing
arthroscopy or other lower limb surgery under spinal anaesthesia. Amounts of 1.6 ml/kg of HS (20 patients) or 13 ml/kg
of 9 mg/ml normal saline (20 patients) were administered for
preloading before spinal anaesthesia with a 10 mg dose of 0.5%
hyperbaric bupivacaine. Etilefrine was administered in order to
maintain mean arterial pressure (MAP) at ⭓80% of its baseline
value. Whole-body impedance cardiography-derived cardiac
index (CI) and extracellular water (ECW) were measured.
Results: There were no significant differences in demographic
data or in the number of blocked segments. ECW remained
similar in both groups despite the much smaller amount of infused free water in the HS group. There were no significant differences between the groups in CI values during the study. The
amount of etilefrine administered was similar in the treatment
groups. Dilution of haematocrit was also similar in both groups.
Conclusion: Hypertonic 75 mg/ml (7.5%) saline is an alternative
for preloading before spinal anaesthesia in situations where excess free water administration is not desired. It is effective in
small doses of 1.6 ml/kg, which increase the extracellular water,
plasma volume and cardiac output, and thus maintain haemodynamic stability during spinal anaesthesia.
I
free water will remain in the body after spinal anaesthesia. The excess free water may be harmful during
postoperative recovery in patients with diminished
cardiac reserve.
The effect of hypertonic saline is rapid and shortlasting. Therefore, it could be a suitable fluid for
preloading before spinal anaesthesia. Only a few
studies have been performed on the use of HS solution in this situation (8, 9). In these, however, 7 ml/
kg of 3 mg/ml (3%) saline was compared with the
same volume of either normal saline or Ringer’s
solution. Thus, the sodium load was markedly
greater in the HS group than in the other groups.
Our purpose was to reduce the water volume in
preloading before spinal anaesthesia. Therefore, we
chose to investigate the effects of the same sodium
load. By using 75 mg/ml (7.5%) saline, the water
load is minimal.
In our previous report, 75 mg/ml (7.5%) hypertonic
of hypertonic saline (HS) causes intravascular and interstitial fluid volume expansion due
to its high osmolality, thus improving the haemodynamics (1). It is inexpensive and involves no risks of
allergic reactions compared with other artificial
plasma expanders. In addition, there is no risk of
transmission of infectious agents as with human
plasma (2). HS solutions of varying concentrations 18–
75 mg/ml (1.8–7.5%) have been investigated in haemorrhagic (3), cardiogenic (4) and refractory hypovolaemic shock (5), and in postoperative use (6).
Spinal anaesthesia produces sympathetic blockade;
systemic vascular resistance decreases, and the blood
pressure may fall (7). Fluid preloading is commonly
used for the prevention of hypotension, and it is
usually well tolerated by healthy young patients. Increased plasma volume is needed throughout the
spinal anaesthesia. If preloading is performed with a
large volume of fluid, a substantial amount of excess
NFUSION
776
Received 29 June, accepted for publication 19 October 2000
Key words: Extracellular water volume; fluid preloading; hypertonic saline; spinal anesthesia.
c Acta Anaesthesiologica Scandinavica 45 (2001)
Effects of hypertonic saline during spinal anaesthesia
saline had a favourable effect on haemodynamics
when used for preloading before spinal anaesthesia
(10). In the present study, we evaluated the data collected during our earlier study to investigate the effects of HS on extracellular water volume and haematocrit. Our purpose was to define the mode of action leading to improved haemodynamics after the
HS infusion (10).
Methods
Forty day-surgery patients scheduled for knee arthroscopy or other lower limb orthopaedic surgery were
randomly allocated according to a list of random digits to two groups of 20 patients (hypertonic saline
(HS) and normal saline (NS) groups) after obtaining
an institutional study approval and written informed
consent. No routine premedication was used. If premedication was needed, 0.05 mg of fentanyl was administered i.v. after the insertion of a venous cannula.
The exclusion criteria included any contraindications
for spinal anaesthesia.
A radial arterial catheter was inserted and the registration of circulation was started in a separate room
for baseline values. CircMonTM B202 (JR Medical Ltd,
Tallinn, Estonia) was used for the measurement of
whole-body impedance cardiography-derived cardiac
output (CO), stroke volume (SV), systemic vascular
resistance (SVR), left cardiac work (LCW) and extracellular water (ECW). Disposable ECG electrodes
(Blue sensor type R-00S, Medicotest A/S, Ølstykke,
Denmark) were used. A pair of electrically connected
current electrodes were placed on the distal parts of
the extremities, just proximal to the wrists and ankles.
Voltage electrodes were 5 cm apart from the current
electrodes (11). Measurements were done in the supine position, and the patient’s limbs were isolated
from the trunk to prevent an electrical connection during the bioimpedance measurements. Blood pressure
was measured noninvasively at 5-min intervals using
Accutorr 4 (Datascope Corp, Montvale, NJ, USA).
ECW (12) was calculated using the equation:
ECWΩK¿H2/R, where H is the height (cm) of the
patient; R is the resistive part of the whole-body bioimpedance (W); and K is the correction factor (KmalesΩ0.078, KfemalesΩ0.095).
In the operating room, a 16-gauge cannula was inserted in a peripheral vein in the cubital fossa. Through
this cannula the patients received either 1.6 ml/kg of
HS (NaCl 75 mg/ml, 7.5%) or 13 ml/kg of NS (NaCl
9 mg/ml, 0.9%), according to randomisation, for fluid
preloading over 10–15 min. All patients received the
same amount of sodium (2 mmol/kg) in this preload-
ing, which was given by the anaesthetic nurse caring
for the patient in the operating room. After the fluid
preloading, saline 4.5 mg/ml (0.45%) infusion was
started as maintenance fluid at the rate of 2 ml kgª1 hª1.
Spinal anaesthesia was induced immediately after
the end of the study fluid infusion. It was performed
using a 27-gauge Quinke-type spinal needle (Spinocan,
B. Braun, Melsungen, Germany) at the L2–3 or L3–4 intervertebral space with the patient in the lateral decubitus position, with the operative side dependent. All patients received 2.0 ml of 0.5% bupivacaine (5 mg/ml,
hyperbaric). The patients were kept in the lateral decubitus position for 5 min and then repositioned in the
supine position. The surgical procedure was started
when the level of sensory blockade was satisfactory.
During the surgical procedure, invasive arterial pressure was monitored continuously using a Hewlet Packard monitor (Hewlett-Packard GmbH, Böblingen, Germany). The baseline value of mean arterial pressure
(MAP) was measured before preloading in the operating room. A 2 mg bolus of etilefrine was administered
i.v. during the course of spinal anaesthesia whenever
MAP fell below 80% of its baseline value. The highest
cutaneous level of the sensory blockade was determined by loss of cold sensation, and the patients were
asked about possible side effects.
Blood samples were taken from the radial arterial
cannula before preloading (baseline); after the patient
was repositioned in the supine position following the
spinal puncture; after the surgical procedure; and after
recovery from the spinal anaesthesia (plantar and dorsiflexion of both ankles recovered). Plasma concentrations of sodium, haematocrit and serum osmolality
were measured. CO, SV, SVR, LCW and ECW were
measured at the same time points.
Before the trial, a power calculation for a 15 mmHg
difference in MAP (1 SD in the previous studies in this
situation) with a probability of a level of 0.05 and power
of 0.80 yielded a sample size of 15–16 patients. Twenty
patients were enrolled in each group.
Statistical analysis was performed using the SPSS for
Windows (version 7.5) (SPSS Inc., Chicago, IL, USA).
The results were analysed using the analysis of variance for repeated measures with group as the factor,
and time as the repeating factor (before preloading;
after the patient was repositioned in the supine position following the spinal puncture; after the surgical
procedure; and after recovery from the spinal anaesthesia). The t-test for independent samples (intergroup
comparison) and t-test for paired samples (intragroup
comparison) were performed at different time points.
Dichotomous variables were tested using the chisquare test. Results are expressed as mean∫SD
777
K. Järvelä et al.
Table 1
Demographic data, effects of spinal anaesthesia and adverse effect
of preloading.
Sex (F/M)
Age (years)
Height (cm)
Weight (kg)
Sensory level of anaesthesia
Duration of spinal anaesthesia (min)
Etilefrine (mg)
Adverse effects* (n)
HS (nΩ20)
NS (nΩ20)
7/13
44∫11
174∫8
81∫16
T6∫2
154∫36
1.0∫2.4
15**
3/17
42∫11
177∫11
79∫12
T7∫2
156∫43
1.0∫2.1
0
* Sensation of heat and compression around the arm.
** P⬍0.001 compared to the NS group.
(mean∫SEM in figures); P⬍0.05 was considered statistically significant.
Results
Equal numbers of patients received either NS or HS,
and there were no differences in the demographic data
or in the number of blocked segments or in the duration
of spinal anaesthesia (Table 1). Duration of surgery did
not differ between the treatment groups. Adverse effects, including the sensation of heat and compression
around the arm during HS infusion and the sense of
thirst, were well-tolerated and disappeared immediately after the completion of the HS infusion (Table 1).
The volume of preload was significantly less in the
HS group compared to the NS group (129∫25 ml vs.
1031∫161 ml, respectively; P⬍0.001). The total infused
volume before and during spinal anaesthesia was also
smaller in the HS group than in the NS group (551∫175
ml vs. 1443∫243 ml, respectively; P⬍0.001). However,
Fig. 1. Extracellular water (ECW) before (1) and after (2) preloading,
after spinal puncture (3), after surgery (4) and after spinal anaesthesia
(5) in the hypertonic saline and normal saline groups. ECW differed
significantly from the baseline after spinal puncture and thereafter in
both groups (P⬍0.05). The groups did not differ at any time point.
ECW remained similar in the treatment groups (Fig. 1).
The ECW increased from 12.0∫1.9 to 12.4∫2.2 l in the
HS group and from 11.9∫1.8 to 12.6∫2.0 l in the NS
group during the study (P⬍0.05 in both groups), but
the groups did not differ at any time point. There was
no notable intraoperative blood loss in either of the
study groups. The groups were similar as regards the
total amount of etilefrine administered (HS:1.0∫2.4 mg
vs. NS:1.0∫2.1 mg) (Table 1). Five patients in both
groups needed etilefrine administration.
There were no significant differences between the
groups in MAP and CI values during the study (Table
Table 2
Haemodynamic data.
MAP
(mmHg)
CI
(l/min/m2)
SV
(ml)
LCWI
(kg ¡ m/m2)
SVRI
(dyn ¡ s/cm5/m2)
Group
Baseline
After preload
After spinal puncture
After surgery
After spinal anaesthesia
HS
NS
HS
NS
HS
NS
HS
NS
HS
NS
95∫15
101∫8
2.82∫0.40
2.76∫0.63
86∫12
85∫17
3.4∫0.6
3.5∫0.9
2678∫613
2962∫675
100∫14
103∫9
3.19∫0.50*
3.02∫0.65*
91∫16*
88∫18*
4.1∫1.0*
4.0∫0.9*
2477∫438
2799∫792
92∫15
97∫10*
3.13∫0.45*
3.14∫0.75*
88∫13
88∫20
3.7∫0.9
3.8∫1.1
2292∫413*
2549∫770*
88∫10*
94∫9*
2.67∫0.56
2.54∫0.48*
88∫11
84∫14
3.0∫0.7*
3.1∫0.7*
2648∫504
2960∫646
89∫11*
95∫9*
2.75∫0.62
2.49∫0.49*
88∫11
81∫15
3.1∫0.7
3.0∫0.6*
2623∫608†
3087∫752
Mean arterial pressure (MAP), cardiac index (CI), stroke volume (SV), left cardiac work index (LCWI) and systemic vascular resistance index
(SVRI).
†
P⬍0.05 compared to the NS group, but the change from the baseline did not differ between the groups.
* P⬍0.05 compared to the baseline.
778
Effects of hypertonic saline during spinal anaesthesia
2). SV and LCWI were also similar in both groups
(Table 2). SVRI was lower in the HS group after spinal
anaesthesia; however, the baseline value was also
slightly lower in the HS group. The change from the
baseline did not differ between the groups (Table 2).
The plasma sodium levels as well as serum osmolality increased after preloading. The maximum level of
plasma sodium after preloading was 150 mmol/l. All
values were within the normal limits after surgery. The
plasma sodium levels and the serum osmolality are
presented in Table 3. The haematocrit value decreased
in both groups, and no significant difference was seen
between the groups (Table 3).
Discussion
We found that 75 mg/ml (7.5%) hypertonic saline was
effective in small doses of 1.6 ml/kg, which increased
the extracellular water and plasma volume, and prevented the haemodynamic changes as effectively as 13
ml/kg of 9 mg/ml (0.9%) normal saline in ASA I–II patients undergoing knee arthroscopy or other lower
limb orthopaedic surgery. When the same amount of
sodium was infused during fluid preloading, the patients required similar amounts of etilefrine in order to
maintain adequate arterial pressure during spinal anaesthesia. This is in line with the results of Veroli and
Benhamou (13). They used saline 5 mg/ml (5%) for preloading before extradural anaesthesia.
The sympathetic nervous blockade did not reach
the level of the heart (T1–T5) in all patients, but the
level of sensory block did not differ between the
treatment groups. Whole-body impedance cardiography (ICGWB) has been shown to be a reliable method
compared with other methods of measuring cardiac
output: comparison with the thermodilution (TD)
and direct Fick methods showed that the ICGWB
measures CO accurately in different conditions (in
the supine position, during head-up tilt, after induction of anaesthesia, and after coronary artery bypass
surgery) (11, 14, 15). The differences in CO values between the ICGWB and TD methods were comparable
to those between the direct Fick and TD methods,
and the repeatability of ICGWB was nearly twice as
good as that of TD (14, 15). Therefore, ICGWB is an
adequate method to estimate CO and its changes.
The exact volume of ECW in man is unknown. In invasive diagnostics, the distribution space of substances
used for ECW volume estimation ranges from about
15% (inulin and mannitol) to 23% (ions such as bromide, chloride) of body weight (16). Bioimpedance-derived ECW volume equations are usually fitted to some
particular dilution method. The CircMonTM device calculates ECW volume on the basis of the equation derived by Kolesnikov et al. (12), which is fitted to thiosulphate space giving ECW values around 16% of body
weight. The ECW values estimated in healthy adults
using this equation (17) agree well with the reference
values reported by Albert (18). The relatively low initial
ECW values in some patients may also be explained by
slight overweight. In addition, relative preoperative
ECW volume deficit may occur in patients undergoing
operation after the preoperative fasting (19). Experimental correlations between whole-body bioimpedance and clinical findings related to ECW have been established recently (17, 20). The solutions infused in our
study have different conductivities, which may have
influenced the bioimpedance-derived ECW. It is difficult to establish the significance of the conductivity-related errors, since the effects are quantitatively complex
involving also varied physiological responses, such as
renal excretion. Logically, the electrical conductivity of
NS roughly equals the average conductivity of the human body, and consequently, it has negligible effect on
the results. As HS is a better conductor than NS, the bioimpedance-derived ECW may be slightly overestimated in this group. As the ECW changes in the HS
and NS groups were in agreement with the results of
the previous studies using dilution techniques (21, 22),
we believe that the differences in conductivity of the
Table 3
Haematocrit (Hct), plasma sodium (P-Na) and serum osmolality (S-Osmol) data.
Hct
P-Na (mmol/l)
S-Osmol (mosm/kg)
Group
Baseline
After preload
After surgery
After spinal anaesthesia
HS
NS
HS
NS
HS
NS
0.41∫0.03
0.41∫0.03
140∫1
140∫1
291∫4
292∫3
0.40∫0.03*
0.39∫0.03*
145∫2†*
140∫1
302∫5†*
292∫3
0.39∫0.03*
0.39∫0.03*
142∫2†*
140∫2
297∫4†*
290∫3*
0.39∫0.03*
0.39∫0.03*
141∫1†*
139∫1*
295∫3†*
290∫3*
†
P⬍0.05 compared to the NS group.
* P⬍0.05 compared to the baseline.
779
K. Järvelä et al.
study fluids did not substantially influence the findings
of the present study. The vasodilatation caused by
spinal anaesthesia results in the fluid distribution from
the central to peripheral vasculature. We do not believe
that this would significantly influence the measured R
in the equation, and thereby increase the calculated
ECW values. We saw a slow positive trend in the ECW
volume, which reflects the physiological distribution of
the study fluid from the intravascular to interstitial
space.
The increase of the plasma sodium concentration
and the serum osmolality was significantly greater in
the HS group, despite the similar amounts of infused
sodium. This created an osmotic gradient between the
extra- and intracellular spaces. The cellular membrane
is semipermeable, allowing only water but no solute
to pass through (22). Sodium is mainly an extracellular electrolyte owing to the active transport mechanism of the cell membrane. Sodium is also the most
important electrolyte participating in the regulation of
the distribution of water. Isotonic 9 mg/ml (0.9%) saline did not change the osmolality of extracellular
water in our patients. Therefore, it increased ECW by
its own volume. Hypertonic 75 mg/ml (7.5%) saline
increases ECW more than its own volume, because it
draws water from the intracellular space in order to
equilibrate the osmotic gradient. This was also seen in
our patients; ECW did not differ between the groups
despite the significant difference in the infused water
volume. Hypotonic 4.5 mg/ml (0.45%) saline infusion
during spinal anaesthesia weakened this effect to
some degree. We did not see any considerable change
in ECW immediately after the infusion of the study
fluids. This can be partly explained by the fact that
the patients’ position was changed when they were
prepared for the surgical procedure, which caused deviations in the baseline impedance independently of
the changes in the fluid status.
Another factor that has probably influenced our results is related to the infusion protocol. We infused
the study fluids during a short period of time, which
means that during this period the fluid remained
mostly in the central circulation. It is known that the
whole-body bioimpedance method underestimates
the central regions in the measurement of ECW (23).
Therefore, the bioimpedance method may not adequately reflect the changes of the intravascular volume. The method is more reliable after the distribution of fluid into the peripheral extracellular space.
Consequently, because of the short time interval between the first two measurements no conclusions can
be drawn from these two phases. The decrease in the
haematocrit values was similar in both groups indi-
780
cating similar increase in the plasma volume. In addition to haemodilution, the decrease in haematocrit
may have been partly due to the shrinkage of erythrocytes in the HS group, since the erythrocytes are one
of the first sources where water is drawn out along
the osmotic gradient (24). The plasma volume increase indicated by haemodilution is more rapid than
the increase in ECW volume because the bioimpedance method is not sensitive to fast intravascular volume increases.
Hypertonic saline increases preload (25) and decreases afterload (26). We were not able to measure
preload because of the noninvasive technique used.
The decrease in SVRI was similar in both groups.
Thus it was rather due to the vasodilator effect of the
spinal anaesthesia than an effect of the hypertonic saline. HS solution also increases myocardial contractility (27, 28). This effect, together with the plasma
volume expansion, could explain its ability to maintain haemodynamic stability during spinal anaesthesia. In our patients, CI was maintained in the HS
group at least at the same level as in the NS group.
Stroke volume was as good in the HS group as in the
NS group.
Preloading with normal saline may require large
fluid volumes, and still fail to maintain adequate arterial pressure (29). We conclude that hypertonic 75
mg/ml (7.5%) saline is an alternative method for preloading before spinal anaesthesia in situations where
excess free water administration is not desired. It is
effective in small doses of 1.6 ml/kg, which increase
the extracellular water, plasma volume and cardiac
output, and thus maintain haemodynamic stability
during spinal anaesthesia.
Acknowledgements
We thank Pirjo Järventausta, RN, and Satu Ruusuvuori, RN, for
their valuable technical assistance. This study was financially
supported by the Medical Research Fund of Tampere University
Hospital, Tampere, Finland.
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Address:
Kati Järvelä, MD
Department of Anaesthesia and Intensive Care
Tampere University Hospital
P.O. Box 2000
FIN-33521 Tampere
Finland
e-mail: kati.jarvela/tays.fi
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