Anesth Analg 2002;94:432-437
© 2002 International Anesthesia Research Society
REGIONAL ANESTHESIA
The Timing of Intravenous Crystalloid Administration and Incidence of Cardiovascular Side Effects During Spinal Anesthesia: The Results from a Randomized Controlled Trial
José L. Mojica, MD*,
Héctor J. Meléndez, MD*, and
Leonelo E. Bautista, PhD
*Department of Surgery, School of Medicine, Universidad Industrial de Santander; and Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences
Address correspondence and reprint requests to Leonelo E. Bautista, 4301 Jones Bridge Road, Room A1039, Bethesda, MD 20852. Address e-mail to lbautista{at}usuhs.mil
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Abstract
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We conducted a randomized clinical trial to evaluate the efficacy of crystalloids in preventing spinal-induced hypotension (SIH) and cardiovascular side effects (CVSE) in a group of surgical patients. Participants were assigned to receive lactated Ringer’s solution at 1–2 mL/min (Placebo group, n = 142); lactated Ringer’s at 20 mL/kg starting 20 min before spinal block (n = 130); or lactated Ringer’s at 20 mL/kg starting at the time of spinal block (n = 132). SIH was defined as a decrease of 
30% in baseline systolic blood pressure, and CVSE as SIH plus nausea, vomiting, or faintness requiring treatment. The incidence of SIH was similar in all treatment groups. Compared to placebo, crystalloid administration at the time of spinal block resulted in a significant reduction in the proportion of patients developing CVSE from 9.9% to 2.3%. The corresponding relative proportion was 0.23 (95% confidence interval, 0.07–0.78; P = 0.019), and one additional case of CVSE was avoided for each 13 patients receiving crystalloids at the time of spinal block instead of placebo. Administration of crystalloids at the time of spinal block seems to be effective because it provides additional intravascular fluids during the period of highest risk of CVSE after spinal anesthesia.
IMPLICATIONS: Crystalloids are frequently administered to nonobstetric patients minutes before spinal anesthesia to prevent cardiovascular side effects (CVSE). This randomized controlled trial shows that although crystalloids administered before spinal block result in no clinical benefit, they significantly reduce the risk of CVSE when administered at the time of spinal block.
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Introduction
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Hypotension is a most common cardiovascular response to spinal anesthesia. More than 30% of the patients undergoing spinal anesthesia develop intraoperative spinal-induced hypotension (SIH) (1). The administration of large volumes of IV crystalloids 15–20 min before spinal anesthesia to prevent SIH has become an increasingly common practice (2–3). However, the efficacy of crystalloid administration before spinal block has been tested mostly in obstetric patients (4–6), and its benefit has been small (3–5,7). Only a small number of studies (8–12) have evaluated the value of crystalloid administration before spinal block versus no crystalloids in general surgery patients. Two studies with very small sample size (8,11) found no significant difference in the incidence of SIH between patients receiving and not receiving crystalloids before spinal block, although blood pressure was significantly increased in the intervention group. No beneficial effect in preventing SIH was observed in two trials among patients 60 yr of age (9,10). However, a large study (12) of patients admitted for orthopedic or general surgery found that crystalloids administered before spinal block significantly reduced the incidence of cardiovascular side effects (CVSE), but only during the first 15 min of anesthesia.
Although the time elapsed between administration of fluids and spinal anesthesia may influence efficacy, no previous study has evaluated the benefits of crystalloid administration at varying times before spinal block. We have conducted a clinical trial to evaluate the efficacy of crystalloids administered 20 min before or at the time of spinal anesthesia, as compared with not administering crystalloids (Placebo group), in preventing SIH and CVSE in a group of general and specialty surgery patients.
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Methods
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The study was approved by the Research Ethics Committee of the School of Medicine, Universidad Industrial de Santander, Bucaramanga, Colombia. Written informed consent was obtained from all participants or their parents. General and specialty surgery patients 11 yr old undergoing spinal anesthesia were eligible for the study, excluding pregnant women, those with a pelvic mass 10 cm, and those with cardiac or pulmonary decompensation. Participants were randomly allocated to receive a continuous IV infusion of lactated Ringer’s solution at a rate of 1–2 mL/min (Placebo group), lactated Ringer’s solution at a rate of 20 mL/kg body weight starting 20 min before the spinal block, or lactated Ringer’s solution at a rate of 20 mL/kg body weight starting at the time of spinal block. Fluids were administered within 6 to 10 min and thereafter all participants received lactated Ringer’s solution at 1–2 mL/min. Treatments were allocated according to a computer-generated random sequence.
Hyperbaric 0.5% bupivacaine without epinephrine was injected between L2-3, L3-4, or L4-5 with the patient seated or resting in the lateral position at 0.25 mg/kg body weight with a maximum total dose of 15 mg. The extension of spinal blockade was assessed by cold temperature discrimination using a wet cotton ball (13). Baseline arterial blood pressure and heart rate were measured immediately before the administration of bupivacaine and monitored thereafter using an automated oscillometer. Measurements at 2, 4, 6, 8, 10, 15, 20, and 25 min were recorded and used for data analysis.
SIH and CVSE were the main study outcomes. In agreement with previous studies (10–12), SIH was defined as a decrease of 30% in baseline systolic blood pressure, which is a change believed to warrant treatment (14,15). At the beginning of the procedure, patients were instructed to report any episode of nausea or faintness occurring during the intervention. Patients were unaware of what treatment they were receiving. CVSE were defined as SIH plus clinical symptoms (nausea, vomiting, or faintness) requiring treatment. CVSE were treated with a bolus of IV ephedrine (100 µg/kg body weight), with additional doses every 5 min, if deemed necessary.
Patient clinical characteristics were described using means and proportions and their corresponding 95% confidence intervals (95% CI). Fisher’s exact test and the F test with a 0.05 significance level were used to test differences in the distribution of dichotomous and continuous variables, respectively. The risk of SIH and CVSE were estimated for each treatment group. The relative risk (RR) and its 95% confidence interval (95% CI) were used to measure the efficacy of each intervention as compared with placebo. Log binomial multiple regression (16) was used to estimate the independent effect of clinical risk factors on the risk of SIH and CVSE. Log binomial regression allows for the estimation of adjusted RR instead of adjusted odds ratios, which frequently overestimate the effect of the exposure.
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Results
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A total of 404 patients were recruited into the study, 142 were assigned to the placebo group, 130 to receive crystalloids before spinal block, and 132 to receive crystalloids at the time of spinal block. Approximately half (53.5%) were men and the mean age was 42 yr (95% CI, 40–44). Four patients were 15 yr old and one was 11 yr old. No biologically significant between-group differences were observed in the distribution of clinical characteristics immediately before spinal block (Table 1). However, as expected, the systolic and mean arterial blood pressure were significantly increased in the group receiving crystalloids 20 min before spinal block, which, contrary to the other treatment groups, had received a significant volume of fluids by the time of injection of bupivacaine (Table 1).
Among all study subjects, the risk of SIH in the first 25 min after spinal anesthesia was 14.6% (95% CI, 11.1%–18.1%), whereas the risk of CVSE was 7.2% (95% CI, 4.6%–9.7%). Although patients who received crystalloids before spinal block had an incidence of SIH 1.52 times more frequent than those in the Placebo group (19.2% versus 12.7%), this difference was not statistically significant (P = 0.143) (Table 2). Subjects who did not receive and those who received crystalloids at the time of spinal block had a similar incidence of SIH (12.1% versus 12.7%) and CVSE (9.2% versus 9.9%, respectively). In contrast, the administration of crystalloids at the time of spinal block resulted in a statistically and clinically significant reduction from 9.9% to 2.3% in the risk of CVSE as compared with administering no additional crystalloids. The corresponding RR was 0.23 (95% CI: 0.07, 0.78; P = 0.019) and one additional case of CVSE was avoided for each 13 patients receiving crystalloid at the time of spinal block instead of no additional crystalloids [1/(0.099–0.023)]. Similar results were obtained when administration at the time of spinal anesthesia was compared to administration before spinal anesthesia (RR, 0.26; 95% CI, 0.08–0.91). Adjustment for body weight and bupivacaine dose in the multivariate analysis did not result in substantial changes in the effect of crystalloids administered before or at the time of spinal block.
The incidence of SIH and CVSE decreased with age up to 40 yr and then increased progressively (Table 3). They also increased with ASA physical status score, from 9.8% in ASA I to 26.7% in ASA III for SIH and from 2.7% to 13.3% for CVSE, respectively (Table 3). Males were also more likely to develop complications than females, and a peak block height above T5 was associated with an increased risk of SIH and CVSE (Table 3).
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Table 3. Risk of Hypotension and Cardiovascular Side Effects by Clinically Relevant Risk Factors in All Study Subjects
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Treatment, age, and block height were the only independent variables associated to the risk of SIH in the multivariate analysis (Table 4). Treatment effects adjusted by age and block height (Table 4) were practically identical to those estimated in the crude analysis (Table 3). Compared with the group of 30–39 yr old, patients <30 yr old had a nonsignificant increase in risk, whereas among patients 50 yr the risk was more than three times higher (Table 4). Also, for each increment of one segment in peak sensory block height (range from T2 to T12), the risk of SIH increased 25% (95% CI, 4%–51%) (Table 3). ASA physical status was also associated with risk of SIH, but only when age was not included in the model. Patients with ASA physical status II–III were two times (RR, 2.32; 95% CI, 1.44–3.76) and four times (RR, 4.03; 95% CI, 1.56–10.36) more likely to develop SIH than patients with ASA I, respectively.
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Table 4. Multivariate Adjusted Relative Risk for Hypotension and Cardiovascular Side Effects by Clinical Risk Factors and Treatment in Patients Undergoing Spinal Anaesthesia
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Regression modeling for CVSE resulted in the selection of the same risk factors as those for SIH (Table 4). Although the age-specific RR had wide confidence intervals, a pattern similar to that described for SIH was observed, and the risk of CVSE was more than four times higher in patients 50 than in those 30–39 yr old (Table 4). In addition, the risk of CVSE increased 1.47 times (P = 0.011) for each increment of one segment in peak sensory block height. When age was excluded from the model, the RR associated with an ASA physical status II–III 3 were 5.33 (95% CI, 2.34–12.13; P < 0.001) and 6.75 (95% CI, 1.50–30.37; P = 0.013), respectively.
Finally, all groups showed a similar pattern of changes in systolic blood pressure with time after bupivacaine administration (Fig. 1). Immediately preceding spinal anesthesia, patients who received crystalloids before spinal block had a higher systolic blood pressure (Fig. 1, Table 1) than other patients. However, beyond 10 min after bupivacaine administration the systolic blood pressure was very similar in patients receiving crystalloids before spinal block and those from the Placebo group, but higher in those receiving crystalloids at the time of spinal block. Time trend changes in diastolic blood pressure were similar to those described for systolic blood pressure.
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Discussion
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Rapid infusion of large volumes of crystalloid is commonly used as prophylaxis for SIH. The goal of administering fluids before spinal block is to increase venous return and preserve central blood volume and cardiac output (17,18), both of which decrease in spinal anesthesia as a consequence of sympathetic blockade (2).
Our study showed that crystalloid administration before spinal block in general and specialty surgery patients does not reduce the incidence of SIH when compared with placebo (1–2 mL/min of lactated Ringer’s solution). This finding is consistent with those from previous studies (8–11) and may be partly explained by the short intravascular half-life of crystalloids (6,12,19). Administering larger volumes of crystalloids may increase the efficacy of fluids administered before spinal block, but such practice is not advisable because of the increased risk of pulmonary edema (20), hemodilution (21), and urinary retention (20). A more rapid administration does not seem to improve the efficacy of crystalloids administered before spinal block and may induce unwanted increases in central venous pressure (5). Replacing colloids for crystalloids seems to be a reasonable approach because colloids remain longer in the vascular space, but there is no conclusive evidence of a decreased incidence of SIH in patients administered colloids (10,22). In addition, colloids are more expensive than crystalloids, and they carry a small but significant risk of anaphylaxis (23).
Administration of crystalloids before spinal block was also ineffective in preventing CVSE in the 25 minutes after spinal block. This question has been evaluated in a previous study in which a beneficial effect of crystalloids was limited to the first 15 minutes after spinal anesthesia (12). These apparently contrasting results could be partly explained because in our study crystalloids were administered within 6 to 10 minutes starting 20 minutes before spinal block, whereas in Arndt et al.’s study (12), crystalloids were administered within the 15 minutes preceding spinal block.
Crystalloid administration at the time of spinal block resulted in an incidence of SIH almost identical to that seen in the Placebo group, but led to a significant reduction in the risk of CVSE as compared with placebo (RR, 0.23; P = 0.019; number needed to treat, 13) or with crystalloids administered before spinal block (RR, 0.26; P = 0.014; number needed to treat, 14). The frequent efficacy of administering crystalloids at the time of spinal block could be explained by the timing of hemodynamic events after spinal anesthesia. Sympathetic nerve blockade is completed within the first 5–10 minutes after administration of bupivacaine (2,24). This period corresponds to the steepest decrease in systolic blood pressure and is followed by a period of increased risk of CVSE. As a matter of fact, 62% of the CVSE cases in our Placebo group developed more than 10 minutes after bupivacaine administration. Similarly, in the study of Arndt et al. (12) Sixty-one percent of the cases occurring in the first 45 minutes of follow-up developed after the first 15 minutes. Therefore, crystalloids administered at the time of spinal block may result in the availability of extra fluids in the intravascular space during the period of highest risk of side effects, leading to timely compensatory cardiovascular changes. In contrast, administering crystalloids before spinal block also increases systolic blood pressure but it is not effective in preventing SIH or CVSE because by the time of highest risk a considerable volume of crystalloids have already diffused to the interstitial compartment and can no longer improve venous return and cardiac output (6,19). The administration of fluids before spinal block may initiate volume overload reflexes that are then counterproductive during the onset of spinal block, whereas administration at the time of spinal block does not require the body to quickly reverse the direction of volume homeostasis mechanisms.
The use of SIH as an outcome may partly explain the negative results observed in trials of crystalloids administered before spinal block (8–11). Although a reduction of 25%–30% in the baseline systolic blood pressure warrants treatment (14,15), most patients can safely tolerate such a decrease (20). Thus, this definition of hypotension may result in too many false positive cases and may dilute the estimate of the efficacy of crystalloids administered before spinal block. On the contrary, CVSE is a more specific and clinically meaningful outcome because it includes SIH plus alarming symptoms usually leading to treatment. Because false positive cases are less likely to occur with CVSE, this outcome seems to be more appropriate for evaluating the efficacy of fluid administration. Because patients were instructed to report nausea and faintness but were unaware of the assigned treatment, it is unlikely that our results were affected by biased reporting of cardiovascular symptoms. Similarly, although the anesthesiologists knew the treatment assigned to the patient, observer bias is not a likely explanation of our findings because blood pressure was measured with an automatic device.
Age and peak block height were the only variables independently associated with the risk of SIH and CVSE in our study. Finding a decreased incidence of both outcomes in the 30–39 year old group and increasing risk in younger as well as older subjects was unexpected. Although an increased risk of SIH in patients over 40 years old has been previously reported (1,25), the actual form of the age-incidence relationship should be further explored in future studies. Changes in autonomic function and decreased cardiac reserve may partly explain age-related changes in the incidence of SIH and CVSE (1).
We found increases of 25% (P = 0.019) in the incidence of SIH and 47% (P = 0.011) in the incidence of CVSE for each increment of one segment in peak sensory block height, and only one case of SIH developed in patients with block height below T6. This finding is consistent with previous reports of a greater decrease in systolic blood pressure and an increased risk of SIH in patients with sensory block level equal or above T5 (1,8). Higher levels of sensory block correlate with higher cephalic spread of sympathetic blockade, greater decrease in venous return and cardiac output, and increased risk of SIH. In contrast, lower levels of sympathetic blockade may result in compensatory vasoconstriction in the upper extremities and decreased risk of SIH.
In summary, our study showed that administering crystalloids at the time of spinal block had a beneficial effect in preventing CVSE in general and specialty surgery patients undergoing spinal anesthesia as compared with administering crystalloids before spinal block or administering no crystalloids. Crystalloid administration at the time of spinal block seems to be more effective because it provides additional intravascular fluids in the period of increased risk of CVSE.
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Accepted for publication September 26, 2001.
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Abstract
Introduction
