Anesth Analg 2008; 106:1002-1007
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e318161520c
REGIONAL ANESTHESIA
The Effects of Prehydration on the Properties of Cerebrospinal Fluid and the Spread of Isobaric Spinal Anesthetic Drug
Byung Seop Shin, MD*,
Justin Sang Ko, MD*,
Mi Sook Gwak, MD*,
Mikyung Yang, MD*,
Chung Su Kim, MD*,
Tae Soo Hahm, MD*,
Sang Min Lee, MD*,
Hyun Sung Cho, MD*,
Sung Tae Kim, MD ,
Ji Hye Kim, MD, and
Gaab Soo Kim, MD*
From the Departments of *Anesthesiology and Pain Medicine, and Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Korea.
Address correspondence and reprint requests to Gaab Soo Kim, MD, Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Korea, 50, Ilwon-Dong, Kangnam-Ku, Seoul, 135-710 Korea. Address e-mail to gskim{at}smc.samsung.co.kr.
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Abstract
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BACKGROUND: In a two-part clinical study, we investigated the effect of the administration of fluids "prehydration" on the physical properties of cerebrospinal fluid (CSF) and intrathecal spread of local anesthetics.
METHODS: First, in the clinical spinal anesthesia study, 68 patients were allocated randomly into the prehydration or nonprehydration groups. One group was prehydrated with 10 mL/kg of lactated Ringer's solution, and spinal anesthesia was performed with 12 mg of 0.5% isobaric tetracaine in all patients at the lumbar level. The arterial blood pressure, heart rate, and sensory block level were assessed. Second, in a magnetic resonance image study, 24 male volunteers were enrolled. CSF motion variables were measured after infusion of 10 mL/kg of lactated Ringer's solution to examine the net flow and volume displacement of the CSF at the L2–3 disk level.
RESULTS: In the clinical study, there were no significant differences in arterial blood pressure, heart rate, and median peak sensory block level between the two groups, but the median time to reach peak sensory block level (26.4 ± 15.7 vs 16.5 ± 9.2 min, P < 0.05) was longer in group P. In posthydration magnetic resonance images, the CSF regurgitant fraction (caudal flow) was significantly increased after hydration, but the stroke volume, absolute stroke volume, mean flux, stroke distance, and mean velocity in the cranial direction were significantly decreased.
CONCLUSIONS: Rapid crystalloid prehydration can affect CSF flow in the lumbar region, reducing cephalic spread of 0.5% isobaric tetracaine and delaying the time to reach the peak sensory level.
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Introduction
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Many clinicians have recommended the rapid administration of fluids before spinal anesthesia (prehydration) to reduce the incidence and severity of hypotension, but its effects are controversial.1–4 Previous studies have focused on the amount5 and type of fluids6,7 or have compared those preventive effects with vasopressors.8
Cerebrospinal fluid (CSF), after its production, is propelled through the ventricular aqueduct and spinal canal. The main bi-directional oscillatory movement of CSF within the cranio-spinal axis arises mainly from the pulsatile motion of brain caused by the arterial systolic pressure waves.8,9 Inflow of blood during the systole creates cranio-caudal CSF flow, and outflow during the diastole promotes caudo-cranial CSF flow.9–11 In addition to this pump flow mechanism, spinal vascular pulsations are considered to be the origin of spinal CSF pulsation in more complex ways.8,12 We hypothesized that the rapid prehydration of relatively large amounts of crystalloid would affect the physical properties of the CSF such as flow and oscillatory motion which, in turn, would influence the spread of local spinal anesthetics in the intrathecal space. A two-stage study was designed to test this hypothesis. In the clinical spinal anesthesia study, the effects of prehydration on the spread of spinal anesthetic drug in patients were investigated and, in the magnetic resonance imaging (MRI) study, its effect on CSF flow and oscillatory motion in volunteers was observed using MRI.
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METHODS
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Our IRB approved this study and informed consent was obtained from the patients and volunteers.
Clinical Spinal Anesthesia Study
Sixty-eight patients scheduled to undergo elective transurethral surgery of the bladder were enrolled. The patients were aged 70 yr or younger, ASA I or II, and began their procedures before 11:00 am. The patients were allocated randomly to one of two groups: the prehydration (P) group or nonprehydration (NP) group. All patients were fasted for 8 h before surgery, and lactated Ringer's solution at a rate of 100 mL/h was started at 6 am through an IV rate flow regulator (Dial-A flo Abbott, Abbott Park, IL). Patients with a history of neurological or spinal diseases, coagulation abnormality, and an inability to identify pinprick stimulation were excluded. No premedication was given before surgery.
The patients in group P received a rapid infusion of 10 mL/kg of lactated Ringer's solution over 10 to 15 min at the waiting area of the operating room. Upon arrival in the operating room, the electrocardiogram, noninvasive arterial blood pressure, and pulse oximetry were monitored and their baseline values were measured. A second anesthesiologist, who was blinded to the fluid administration status, performed spinal anesthesia at the third lumbar interspace (L3–4) using the midline approach with the patients in the right lateral decubitus position. A 25-gauge Whitacre spinal needle (BD Whitacre needle, BD Medical System, NJ) was used with the orifice of the spinal needle directed to the left. Four milliliters of CSF was withdrawn through the Whitacre needle and used to dissolve 20 mg of crystalline tetracaine hydrochloride (Pantocainesterile, Daehan Med Co, Seoul, Korea) to make 0.5% isobaric tetracaine solution. From this mixture, 12 mg (2.4 mL) was injected slowly into the intrathecal space over a 30-s period. The patients were placed into the supine position, and 3 L/min of oxygen was delivered through nasal prongs. After 5 min, the patients were placed into the lithotomy position and the operating table was maintained horizontally throughout the procedure. The patients received lactated Ringer's solution at a rate of 100 mL/h throughout the procedure, as well as during their stay in the postanesthesia care unit. The sensory block levels were checked by pinprick using a 25-gauge Whitacre needle. The sensory block levels were recorded every 5 min until 30 min after spinal anesthesia and then every 15 min for a 90-min period. The peripheral oxygen saturation, arterial blood pressure, and heart rate were recorded at 5-min intervals until 90 min after the spinal anesthesia. If the mean arterial blood pressure had decreased by more than 30% from the baseline level (hypotension), ephedrine 5 mg was injected immediately. Atropine 0.5 mg was injected if the heart rate had decreased to <50/min (bradycardia). Arterial blood pressures, heart rates, and incidence of hypotension and bradycardia were measured.
MRI Study
Twenty-four male volunteers (23–42 yr; Body Mass Index (BMI): 18.5–24.9 kg/m2) were included. Patients with a history of neurological disease or spinal deformities were excluded. Women volunteers were not included in this study because the CSF production rate has been reported to be influenced by menstrual cycle. All the MRIs were taken between 7:00 pm and 8:00 pm in order to minimize any possible influences of circadian rhythm.13,14 The first MRIs and their variables were the control values. Immediately afterward, a lactated Ringer's solution 10 mL/kg was rapidly infused over a 10–15-min period. Thirty minutes after the start of the crystalloid infusion, the volunteers underwent their second MRI. The 30-min interval between the two MRIs was allotted in order to match the time range between the start of prehydration and the completion of the intrathecal injection of local anesthetic in the patients in the clinical spinal anesthesia study. Quantitative assessment of CSF motion was performed following previously reported methods.15–18 The sagittal turbo spin echo T2 weighted images of the thoracolumbar spine were obtained to determine the anatomical levels of flow quantification as well as to exclude spinal canal stenosis. Cardiac gated, phase-contrast cine high resolution MRI was performed using a 3 Tesla MR scanner (Achieva, Philips Medical System, Best, The Netherlands) to measure the flow and motion of the lumbar CSF. From these images, the best offset for the midline section of the L2–3 level was determined. A quantitative assessment of CSF flow movement was then performed using the 2D T1-FFE sequence quantitative-flow technique with the following image acquisition variables: repetition time/echo time = 13/7.9 ms, flip angle = 15 degree, scan orientation = transverse, field of view = 150 mm, slice thickness = 10 mm, matrix size = 224 x 224, velocity encoding = 2 cm/s, cardiac phase = 30, phase contrast flow direction = foot to head. The acquisition time, which depends on heart rate, was approximately 5 to 6 min. The cardiac cycle in this study was determined using a peripheral gating trigger. In order to examine the net flow and volume displacement of the CSF at the L2–3 disk level, various CSF motion variables (regurgitant fraction, stroke volume, absolute stroke volume, mean flux, stroke distance, and mean velocity) were measured on the axial slices using the methods of the circular regions of interest (ROIs) within the entire thecal sac, including the cauda equina. The definitions of the parameters are as follows: stroke volume (mL); average of the CSF volume moving caudally during systole and cephalically during diastole, regurgitant fraction (%); the ratio of caudal to cranial flow of the CSF per single stroke volume, absolute stroke volume (mL); the integral over time for the volumetric flow rate, and flux (mL/s); "mean velocity x area" or the CSF volume that passes the contour per second.11,12,19
Two radiologists, who were blinded to the aims of this study, manually placed circular ROIs in triplicate at different sessions for each sample, respectively, and obtained the mean values of the circular ROIs. Analysis and data post-processing were performed at a workstation, and the measured signal changes were converted to a velocity, and the amount of flow was determined using an analysis program (View Forum, Philips Medical System, Best, The Netherlands). The acquired data were evaluated to determine if the CSF flow would change at the level of the L2–3 disk space by comparing the variables of the CSF pulsatile motion before and after the rapid administration of lactated Ringer's solution. In addition, we assessed whether there is any correlation between BMI and CSF pulsatile motion between pre and posthydration.
Statistical analysis was performed using SAS software (version 8.1, SAS Institute, Cary, NC). The comparisons were performed using a t-test for the parametric data and a Mann–Whitney test for the nonparametric data. Ephedrine and atropine use were compared using the  2 method. The sample size of the patients in the clinical study was determined by power analysis ( = 0.05, β = 0.80), which showed that 34 patients would be required in each group to reveal a significant difference in time to reach the peak sensory block level between the two groups. This was based on a previous study measuring the time from injection of 0.5% isobaric tetracaine to highest level of sensory blockade in lithotomy position.15 In the MRI study, the necessary sample size was estimated based on a pilot study of 10 volunteers. Power analysis indicated that 24 volunteers would be needed to detect a possible difference of 20% in the regurgitant fraction among the oscillatory motion profiles obtained before and after administering the fluid. The correlation between BMI and CSF pulsatile motion before and after the rapid administration of lactated Ringer's solution was evaluated using Spearman's correlation analysis with Bonferroni's correction. A P value <0.05 was considered significant.
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RESULTS
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Clinical Spinal Anesthesia Study
There were no significant differences between the two groups in terms of age, weight, height, and gender (Table 1). The amount of fluid remaining at the waiting area of the operating rooms was also similar in the two groups (717.4 ± 228.1 mL in group P vs 806.3 ± 117.2 mL in group NP). Arterial blood pressures and heart rates were similar in both groups throughout the study (Fig. 1). The median (range) peak sensory block levels was T8 (T3–11) and T7 (T3–12) in groups P and NP, respectively, and there was no significant difference. However, the time to reach the peak sensory block level was significantly longer in group P (Table 2). The time to two-dermatome regression from peak sensory block level was similar in both groups. There were no significant differences between groups in the frequency of hypotension or bradycardia requiring treatment (Table 2). No patient was transfused due to hemorrhage.
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Table 1. Characteristics of the Patients in the Clinical Study and Volunteers in the Magnetic Resonance Imaging (MRI) Study
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Figure 1. Change in mean arterial blood pressure and heart rate during isobaric 0.5% tetracaine spinal anesthesia. There were no significant differences in the mean arterial blood pressures and heart rate between the prehydration and nonprehydration group throughout the study period.
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MRI Study
Patient demographics in the MRI study differed significantly from those in the clinical anesthesia study (Table 1). The regurgitant fraction showed a significant increase in the second MRI taken after rapid fluid administration (P = 0.011). Because the software setting of the Q-flow MRI study examined the standard direction of CSF flow from caudal to cephalic, the increased regurgitant fraction signifies reduced cephalad but increased caudal CSF flow at the lumbar levels after rapid administration of lactated Ringer's solution. Data analysis revealed attenuation of oscillatory motion of the CSF, as evidenced by the statistically significant decreases in stroke volume (P = 0.009), absolute stroke volume (P = 0.017), mean flux (P = 0.013), stroke distance (P = 0.012), and mean velocity (P = 0.001) after administering the fluid (Table 3, Fig. 2). However, no correlation was observed between BMI and CSF pulsatile motion before and after the rapid administration of lactated Ringer's solution.
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Table 3. Comparison of the Variables of Cerebrospinal Fluid (CSF) Dynamics Before and After Rapid Crystalloids Hydration in Magnetic Resonance Imaging (MRI) Study
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Figure 2. Examples of a change in cerebrospinal fluid oscillatory motion of one volunteer. Compared with the time-flux curves before administering crystalloid (A), the time-flux curves showed a significant change in the shape of the graph with an increased regurgitant fraction, decreased stroke volume and mean flux, stroke distance, mean velocity after rapid administration of crystalloids (B).
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DISCUSSION
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The main finding of this study is that rapid administration of crystalloids produced a significant delay in time to reach peak sensory block level after intrathecal injection of 0.5% isobaric tetracaine. The MRI study of CSF movement in the lumbar region revealed the attenuation of CSF oscillatory motion and the comitant decrease in CSF cephalic movement 30 min after prehydration. The major mechanisms for the spread of intrathecal anesthetic drugs have been attributed to several factors including the displacement of CSF caused by the currents of injectate, interactions with CSF according to the differences in density, and diffusion through CSF. For an isobaric anesthetic drug, most of the injectate has been demonstrated to remain near the point of injection. However, diffusion, which is affected by CSF movement, is thought to have a major effect on its intrathecal spread. The physical properties of CSF, such as the mixing mechanism created by its motion, can affect the rate of diffusion and thus play a major role in the spread of an isobaric spinal anesthetic drug.
The development of cardiac gated, phase-contrast cine high resolution MRI has allowed the generation of velocity MRIs and yielded quantitative information on CSF flow. Under the quantitative assessment of CSF oscillatory motion, this MRI study showed that CSF flow decreases significantly in the cephalic direction with a concomitant increase in the regurgitant fraction after rapid prehydration. Using cardiac gated, phase-contrast cine high resolution MRI, Higuchi et al.20 reported that the velocity of CSF influenced the extent and duration of plain bupivacaine spinal anesthesia. However, their study differed from ours because CSF velocity and volume were not always determined whenever spinal anesthesia was administered. Cooper et al.21 suggested that vasopressors might affect sensory block levels during spinal anesthesia with plain 0.5% levobupivacaine, and assumed that significant increase in the right atrial pressure by phenylephrine-induced vasoconstriction caused an increase in intracranial pressure and subsequently promoted a significant shift in CSF from the cranial to spinal cavity. Moreover, the transient increase in CSF flow might be ascribed to the short intravascular half-life of the crystalloids (20–30 min), as evidenced by the lack of a difference in time to two-segment regression from the peak sensory block level between the two groups.
Although regurgitant fraction increased, other variables (stroke volume, mean flux, stroke distance, and mean velocity) significantly decreased after rapid crystolloids hydration. From these results, the attenuation of oscillatory motion of lumbar CSF can be another possible explanation for the delay in time to reach the peak sensory block level after rapid hydration. Baledent et al.22 reported that extracerebral CSF was first to respond to brain volume expansion, and the expansion of the lumbar thecal sac and compression of the epidural venous plexus promoted instantaneous and large CSF venting from the foramen magnum during arterial systole. Therefore, a transiently increased spinal CSF volume might result in reduced compliance of the blinded thecal sac. This reduced compliance might attenuate the oscillatory motion of lumbar CSF, and subsequently impede the normal mixing and spread of an isobaric spinal anesthetic drug. One possible limitation of this study is the difference in patients’ ages between the clinical and MRI studies. The mean rate of CSF production in the elderly is significantly lower (<50%) than young individuals.23 However, when the values of CSF motion profiles of this MRI study are considered, we believe that the amount of CSF displacement within the lumbar thecal sac after rapid administration of fluid, even after a decrease of more than 50%, is adequate to explain the results of the clinical study. Another limitation is that we did not directly evaluate CSF flow change after spinal anesthesia. Spinal anesthesia can cause significant hemodynamic alterations, such as hypotension and arrhythmia which, in turn, can influence CSF flow at the lumbar level by reducing arterial pulsation. The efficacy of prehydration in preventing spinal anesthesia-induced hypotension has been questioned,2,24,25 and this clinical study did not show significant differences in hemodynamic values between the two groups, even though this was not the aim of the clinical study.
In conclusion, the rapid administration of crystalloids affects spinal CSF flow and oscillatory motion at the lumbar level, which may contribute to a decrease in the cephalic spread rate of sensory block with isobaric spinal anesthetic drug. Therefore, prehydration may be one of the factors influencing the spread rate of isobaric spinal anesthetic drugs associated with changes in the physical properties of the CSF.
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Footnotes
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Accepted for publication October 31, 2007.
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Abstract
Introduction
