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*Département d'Anesthésie, Hôpital Central, Nancy;
Laboratoire d'Anesthésie, Université Paris-Sud, Faculté de Médecine du Kremlin-Bicêtre, Le Kremlin-Bicêtre;
Département d'Anesthésie, Hôtel Dieu, Nantes; and
§Département d'Anesthésie, Hôpital Antoine Béclère, Clamart, France
Address correspondence and reprint requests to Hervé Bouaziz, MD, Département d'Anesthésie, Hôpital Central, F-54035 Nancy Cedex, France.
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Abstract |
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Implications: In young rabbits, any decrease in blood pressure was followed by a decrease in spinal cord blood flow, a decrease that did not correlate to the use of epinephrine and was not observed in adult animals. These data suggest that blood pressure should be monitored closely to promptly treat any decrease in blood pressure when combined epidural-general anesthesia is used in children.
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Introduction |
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Because most regional anesthetic procedures in pediatric practice are performed in combination with general anesthesia, the purpose of this study was to determine the effect of epinephrine (5 µg/mL) added to epidural lidocaine on the spinal cord blood flow (SCBF) of anesthetized rabbits of varying ages.
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Methods |
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The femoral artery catheter was connected to a transducer to record arterial blood pressure. After a 15-min period to obtain stable baseline conditions, adult rabbits received either 1 mL of saline, 1 mL of 2% plain lidocaine (Astra, Courbevoie, France), or 1 mL of 2% lidocaine with epinephrine 1:200,000 (5 µg/mL) epidurally over 30 s. The 3-wk-old rabbits received 0.3 mL of the same solutions via the same route. Despite the difficulty in evaluating the sensory level under general anesthesia, we estimated the upper sensory level as previously described (5). One milliliter of blood was sampled via the femoral artery 30 min after epidural injection, and lidocaine was assayed in plasma using gas chromatography.
Two additional groups of young (n = 5) and adult (n = 6) rabbits receiving epinephrine 5 µg/mL in saline were also studied to determine the effect of epinephrine alone on SCBF.
To determine regional blood flow, 15.5 µm diameter colored microspheres (Dye-Trak; Triton Technology, Bioseb, France) were injected through the left ventricular catheter 10 min before and 7.5 and 30 min after epidural injection. Adult rabbits received 900,000 colored microspheres (yellow, white, and red injected in a random order) using a Harvard pump (Harvard Apparatus), whereas young rabbits received 225,000 colored microspheres (6,7). Simultaneous to microsphere injection, reference sampling from the femoral artery was begun at a constant rate of 0.84 mL/min for 75 s using a Harvard pump (Harvard Apparatus). Four milliliters of saline was infused thereafter to compensate for the blood volume withdrawn.
After the study, animals were killed using heavy sedation with IV pentobarbital. A dorsal laminectomy was performed, and the correct location of the epidural catheter was confirmed by direct vision. The organs (brain, heart, kidneys, and the L6-7 segment of the spinal cord) were dissected and cut into samples weighing 150–300 mg each. Colored microspheres were assayed by using high-pressure liquid chromatography (6).
Exclusion criteria included incorrect location of the epidural catheter, as determined at autopsy, and inadequate sphere injection or mixing in blood, as assessed by comparing left and right renal blood flow.
Cardiac output (CO) was determined by: CO = Qref x NSinj/NSblood where Qref = rate of reference blood sampling (mL/min) and NSinj and NSblood = number of spheres injected and number of spheres measured in the blood, respectively. CO is expressed in mL · min-1 · kg-1. Regional blood flow values were determined by: Qorg = NSorg x Qref/NSblood where NSorg = number of spheres measured in each organ sample. Qorg is expressed in mL · min-1 · g-1.
We compared the two groups (adult and young rabbits) for basal values using nested two-way analysis of variance (ANOVA); thereafter, the two groups were analyzed separately. Whatever the result of this first comparison, demographic data and basal values were compared within each group using one-way ANOVA. Hemodynamic and flow values were compared among subgroups and time points by using two-way ANOVA for repeated measures, followed by a Neuman-Keuls test when appropriate. We tested the correlation between change in SCBF (flow at time Tn + 1 - flow at time Tn) over changes in mean arterial pressure (MAP) (MAP at time Tn + 1 - MAP at time Tn) using linear regression. ANOVA was used to test the within-group (adult and young rabbits) significance of the linear regression (8). Data are expressed as mean ± SEM unless otherwise specified.
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Results |
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Adult Rabbits
Baseline values of MAP were not different among subgroups (saline 79 ± 6, plain lidocaine 78 ± 3, lidocaine with epinephrine 71 ± 2 mm Hg). MAP significantly decreased after the epidural administration of lidocaine with and without epinephrine (Fig. 1).
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No difference in CO and regional flows were detected among subgroups at baseline, before any epidural injection (Table 2). However, baseline CO, SCBF, and coronary blood flows were significantly higher in young versus older rabbits, whereas baseline renal and cerebral blood flows were similar to those measured in adult rabbits. CO significantly decreased with time in young rabbits. No variation in coronary and kidney blood flows was noticed. Contrary to what was observed in adult rabbits, SCBF significantly decreased with time. A slight but significant increase in cerebral blood flow with time was also found in young rabbits. No difference among subgroups was found in either SCBF or cerebral blood flow in young rabbits. In contrast to adult rabbits, a significant positive correlation was found between changes in MAP and changes in SCBF after the administration of plain lidocaine (
flow = 0.016 x MAP - 0.11; r2 = 0.37) and after the administration of lidocaine with epinephrine (flow = 0.009 x MAP + 0.02; r2 = 0.45). No departure from parallelism was detected between these two subgroups.
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With or without epinephrine, lidocaine plasma concentrations were significantly lower in young rabbits (1.28 ± 0.54 or 1.60 ± 0.44 µg/mL, respectively) than those in adult rabbits (3.00 ± 1.67 or 4.07 ± 1.73 µg/mL, respectively) (mean ± SD).
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Discussion |
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In adult rabbits, the epidural administration of lidocaine, with or without epinephrine, induced a significant reduction in MAP (Fig. 1) with a magnitude and time course in accordance with a previous study using the same animal model (5). Despite this finding, regional blood flows did not significantly change in adult rabbits over time. No correlation was found between changes in MAP and changes in SCBF.
There are conflicting data concerning the SCBF responses to subarachnoid or extradural injection of local anesthetics with or without epinephrine. Indeed, no change in SCBF was detected after the subarachnoid administration of lidocaine, with or without epinephrine, in anesthetized cats (10) or dogs1; after the subarachnoid administration of tetracaine, with or without epinephrine, in dogs2; or after the subarachnoid administration of lidocaine, mepivacaine, and tetracaine, with or without epinephrine, in cats.3 Surprisingly, an increase in SCBF has been shown after the subarachnoid administration of plain lidocaine (but not lidocaine with epinephrine) in the dog (11). Conversely, a significant decrease in SCBF after the subarachnoid administration of bupivacaine has been reported in rats (12) and in dogs (13). Similarly, Dohi et al. (14) showed that subarachnoid lidocaine with phenylephrine, but not plain lidocaine, diminished SCBF in dogs. When injected epidurally, lidocaine has been shown to decrease SCBF in the dog (15). Malinovsky et al. (16) showed that both epidural plain 0.5% bupivacaine and epidural bupivacaine-loaded microspheres decreased SCBF in awake rabbits. Several factors may explain these discrepancies: 1) the placement of the epidural catheter using a surgical or a percutaneous technique leading to varying degrees of noxious stimulation; 2) the association of general anesthesia in some studies; 3) the method used to measure regional blood flows; 4) different drugs, such as bupivacaine, lidocaine, mepivacaine, or tetracaine; and 5) the site of injection (subarachnoid versus epidural). Moreover, the addition of vasoactive drugs (epinephrine, phenylephrine, etc.) may have additional local and/or systemic effects. In fact, it is well known that the spinal cord has a limited blood supply and is vulnerable to ischemia (17). In our study, adult rabbit MAP was maintained between 50 and 150 mm Hg, which is the range of pressure in which, via autoregulation, the blood flow of preserved organs (brain, kidney, heart, spinal cord) remains unchanged (17,18). This may explain the absence of variation in the SCBF in our adult rabbit group despite a significant reduction in MAP (18,19).
In young rabbits, the decrease in MAP observed after epidural lidocaine administration was much less than that in adult rabbits. In pediatric patients, epidural anesthesia produces little to no change in blood pressure (20,21). We used lidocaine 2% (which is rarely used in pediatric practice) to increase the incidence of adverse effects. The resulting block induced a significant decrease in MAP in the two subgroups receiving lidocaine, but this decrease was only significant 7.5 min after lidocaine injection in the plain lidocaine group, compared with 7.5 and 30 min after injection in the lidocaine with epinephrine group (Fig. 1). At these specific times, the average MAP was <50 mm Hg in these two subgroups. Contrary to what was observed in adult rabbits, a significant reduction in SCBF was then noticed. However, in the two subgroups of young rabbits receiving lidocaine, changes in SCBF were correlated to changes in MAP with 37% and 45% of the variation in flow explained by the variation in MAP in the plain lidocaine subgroup and in the lidocaine with epinephrine subgroup, respectively. This is likely related to the fact that, because of the lower values of MAP at baseline, a decrease in MAP <50 mm Hg is more frequent in young rabbits than in adults and is rapidly followed by a loss of autoregulation (17–19). However, young rabbits had a significantly higher basal SCBF than adults, and the mean SCBF after lidocaine injection was greater than the corresponding flow in adults. SCBF then decreased in young rabbits, and this decrease was parallel to the decrease in MAP.
In additional groups of rabbits receiving epinephrine alone, SCBF did not change throughout the study in adult or young animals. The increase in CO with time observed in adult rabbits and the increase in MAP observed in young rabbits may be related to a lightning of anesthesia. However, SCBF remains stable even when expressed as a fraction of CO. Thus, the hypotension observed in the group receiving 2% lidocaine epidurally in combination with general anesthesia seems to be the main factor that led to decreased SCBF in young rabbits.
Changes in SCBF usually parallel changes in cerebral blood flow (22). It is therefore not surprising that cerebral blood flow remains stable in adult rabbits, as was observed for SCBF. Surprisingly, cerebral blood flow increased in young rabbits. It is known that cerebral blood flow is preserved in infants during caudal anesthesia (23). Using a Doppler technique in 6-mo-old infants, Payen et al. (23) showed that caudal anesthesia with bupivacaine 3.25 mg/kg performed during light general anesthesia did not decrease cerebral blood flow, although a marked reduction in brachial blood flow was observed (23). We observed a paradoxical increase in cerebral blood flow in young rabbits, which might be attributed to lightning of general anesthesia during the course of the experiment.
Although this study can be criticized because it is not general practice to maintain general anesthesia with pentobarbital in pediatric anesthesia, the same technique of anesthesia has been used for all of our groups of rabbits.
In conclusion, lidocaine 2% with or without 1:200,000 epinephrine induced a decrease in SCBF in young, but not in adult, rabbits. This reduction of SCBF correlated to a decrease in MAP likely due to the association of epidural and general anesthesia. SCBF did not decrease with blood pressure in the corresponding adult rabbit groups. However, because of a higher basal blood pressure, adult rabbits maintained their MAP >50 mm Hg, which is considered the critical value of autoregulation (17–19). The decrease in SCBF observed in young rabbits did not correlate to the use of epinephrine. This negative result may be due to a lack of power of the experiment; in any case, epinephrine did not seem to be the primary cause of decreased SCBF in young rabbits. Finally, although our results cannot be directly applied to humans, and although hypotension is rare in infants and children receiving epidural anesthesia (20,21,23), this study suggests that, when combined with general anesthesia, a reduction in blood pressure might reduce SCBF. Not only should blood pressure be carefully monitored, but events that might cause a reduction in blood pressure should be avoided, and any reduction in blood pressure should be immediately and effectively treated.
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Acknowledgments |
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We thank Mrs. Régine Le Guen for her expert technical assistance on the high-performance liquid chromatography measurement of colored microspheres.
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Footnotes |
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2 Kozody R, Cumming M, Palahniuk RJ. Spinal cord bloodflow following subarachnoid block with and without epinephrine [abstract]. Anesth Analg 1984;63:238.
3 Smith SL, Albin MS, Watson WA, et al. Spinal cord and cerebral bloodflow responses to intrathecal local anesthetics with and without epinephrine [abstract]. Anesthesiology 1993;59:312.
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References |
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= plain lidocaine, 
= lidocaine with epinephrine 1:200,000. *P < 0.05 versus all other time points within the subgroup. §P < 0.05 versus T0 and T3.
