Anesth Analg 1999;88:1322
© 1999 International Anesthesia Research Society
REGIONAL ANESTHESIA AND PAIN MANAGEMENT
Epidural Phenylephrine Attenuates Hypotension Induced by Alkalinized Lidocaine Epidural Anesthesia
Jen-Kun Cheng, MD*,
Mu-Hsi Pan, MD*,
Kuo-Hwa Wu, MD*,
Martin Saiwong Mok, MD
, and
Tze-Taur Wei, MD*
*Department of Anesthesia, Mackay Memorial Hospital, Taipei and Taitung, Taiwan, Republic of China; and
Department of Anesthesiology, University of Southern California, Los Angeles, California
Address correspondence and reprint requests to Dr. Jen-Kun Cheng, Department of Anesthesia, Mackay Memorial Hospital, No. 92, Sec. 2, Chung Shan North Road, Taipei, Taiwan, 10449, Republic of China. Address e-mail to jkcheng{at}usa.net
 |
Abstract
|
|---|
In this double-blinded, randomized study, we examined the hemodynamic effects of lumbar epidural injection of alkalinized lidocaine with phenylephrine in 81 patients undergoing inguinal herniorrhaphy. Patients assigned to four equal groups received 20 mL of alkalinized lidocaine (17 mL of 2% lidocaine + 3 mL of 7% sodium bicarbonate) with one of four doses of phenylephrine: 0 (Group 1), 50 (Group 2), 100 (Group 3), or 200 µg (Group 4) injected via a lumbar epidural catheter. Blood pressure, heart rate, and skin temperature on the foot were recorded every 5 min for 1 h after injection and were compared among groups. Hypotension was defined as mean arterial pressure < 80% of baseline. The incidence of hypotension was 45%, 55%, 35%, and 15% in Groups 1–4, respectively. Patients in Group 4 showed the smallest reduction in blood pressure compared with Groups 1 and 2 (one-sided Fisher's exact test, P < 0.05). We conclude that the 200-µg dose of epidural phenylephrine (1:100,000 concentration) reduced the incidence of hypotension after epidural anesthesia with alkalinized lidocaine.
Implications: Hypotension after epidural anesthesia is common in general clinical practice. Phenylephrine administered epidurally in combination with alkalinized lidocaine may reduce the incidence of hypotension.
|
Introduction
|
|---|
Like ephedrine, IV phenylephrine (PHE) has been used to treat hypotension induced by epidural anesthesia (1,2). In 1973, Stanton-Hicks et al. (3) showed that 50 µg/mL epidural PHE (total dose 900-1100 µg) increased mean arterial pressure after lidocaine epidural block, presumably through its 
1-adrenergic vasoconstricting effect. Since then, there have been no reports regarding the use of epidural PHE. Recently, alkalinization of local anesthetics has gained acceptance as a method of shortening the onset of epidural anesthesia (4–6). This could also hasten the onset of sympathetic block and worsen hypotension. The purpose of this study was to determine whether combining epidural PHE with alkalinized lidocaine can reduce the incidence of hypotension in epidural anesthesia.
|
Methods
|
|---|
After obtaining hospital review board approval and patient consent, 81 adult patients, ASA physical status I or II, undergoing inguinal herniorrhaphy under lumbar epidural anesthesia were assigned, using a randomized, double-blinded design, to receive epidural alkalinized lidocaine with one of four doses of PHE (0, 50, 100, or 200 µg in Groups 1–4, respectively).
No premedication was given. Patients received 500 mL of lactated Ringer's solution before epidural anesthesia, which was performed with the patient in the lateral decubitus position. After skin infiltration with 1% lidocaine, an 18-gauge Tuohy needle was inserted into the epidural space at L3-4 or L4-5 using the midline approach with the loss of resistance technique, followed by the insertion of a 21-gauge epidural catheter. A test dose of 3 mL of 2% lidocaine with 1:200,000 epinephrine was then injected via the epidural catheter. After 5 min, a mixture of 17 mL of 2% lidocaine and 3 mL of 7% sodium bicarbonate (final pH 7.05 ± 0.01) with one of the four doses of PHE (all in 0.5 mL of isotonic sodium chloride solution) was injected over 3–4 min.
Blood pressure (BP), heart rate (HR), and foot skin temperature were measured with the patient in the supine position 1 min before the epidural injection and every 5 min thereafter for 1 h. Pinprick testing was performed at 20- and 30-min intervals after the epidural injection to determine the highest level of sensory block. Incremental doses of 4–8 mg of ephedrine were administered IV to restore BP if systolic arterial pressure was <80% of the baseline values or <100 mm Hg. Hypotension was defined as mean arterial pressure (MAP) <80% of the baseline. Systolic and diastolic BP and HR were measured with automatic blood pressure cuff and continuous electrocardiogram monitor (Life Scope 9; Nihon Kohden, Tokyo, Japan). MAP was calculated by adding one third of the pulse pressure to the diastolic arterial pressure. To determine whether PHE-induced vasoconstriction would be reflected in the change of lower limb skin blood flow, the foot skin temperature was measured with the thermoprobe (Life Scope 6; Nihon Kohden) attached to the dorsum of the first interdigital space of the right foot with surgical tape.
Patient characteristics and baseline hemodynamic variables among groups were compared using a one-way analysis of variance (ANOVA). Sequential MAP and HR measurements were tested for the main effects of dose, time, and their interaction (dose x time) using repeated-measures ANOVA. The Kruskal-Wallis test was used to compare the highest sensory block level among the four groups. Spearman rank correlations were used to test for associations between the PHE doses and the presence of hypotension or ephedrine use. One-sided Fisher's exact tests were used to test for pairwise differences among groups and their effects. Throughout the study, Bonferroni corrections were made for multiple comparisons only when the overall effects for the Spearman rank correlation or the ANOVA analysis were not significant. P < 0.05 was considered statistically significant.
|
Results
|
|---|
In this study, one patient experienced an episode of severe hypertension (BP 212/146 mm Hg) and mental confusion, which was suspected to be due to direct absorption of the 200-µg PHE-alkalinized lidocaine mixture through a lacerated epidural vessel. Droperidol was injected IV, and the patient gradually recovered without sequelae. This patient was not included in our data analysis.
There were no significant differences among groups with regard to patient demographics, baseline hemodynamic variables, and the highest sensory block level (Table 1).
The repeated-measures ANOVAs found the overall effect of time to be very significant for both MAP and HR (P = 0.0001). Overall dose effects were not significant for either MAP or HR. The interaction between dose and time (dose x time) for MAP was not significant. However, post hoc comparisons did find significant differences between Groups 2 and 4 at 15 min (P = 0.0005) and between Groups 1 and 4 at 20 min (P = 0.0006) (Fig. 1). In contrast to MAP, the HR analysis found a significant dose x time interaction (P = 0.0148). All significant post hoc comparisons among groups for HR are shown in Figure 2. At no time did the mean HR of any group differ by >10% from their baseline values (Fig. 2). Corrections were made for multiple comparisons when appropriate, as described above.
View larger version (21K):
[in this window]
[in a new window]
|
Figure 1. Mean percent change of baseline mean arterial pressure (MAP) over time after the administration of epidural phenylephrine (PHE)-alkalinized lidocaine. Each value is expressed as mean ± SEM (n = 20 in each group). *P < 0.05 compared with Group 1. P < 0.05 compared with Group 2.
|
|
View larger version (22K):
[in this window]
[in a new window]
|
Figure 2. Mean percent change of baseline heart rate (HR) over time after the administration of epidural phenylephrine (PHE)-alkalinized lidocaine. Each value is expressed as mean ± SEM (n = 20 in each group). *P < 0.05 compared with Group 1.
|
|
Hypotension and ephedrine use were found to be negatively correlated with PHE dose (hypotension: r = -0.254, P = 0.023; ephedrine use: r = -0.275, P = 0.013). Groups 1 and 2 differed significantly from Group 4 with respect to both hypotension (Group 1 versus Group 4: P = 0.041; Group 2 versus Group 4: P = 0.0094) and ephedrine use (Group 1 versus Group 4: P = 0.032; Group 2 versus Group 4: P = 0.032). No other group differences were found (Table 2).
Foot temperatures increased in all groups, and there were no significant differences among the four groups (baseline temperatures for Groups 1–4: 28.6 ± 0.6, 28.0 ± 0.6, 27.8 ± 0.5, 27.8 ± 0.4°C; end temperatures for Groups 1–4: 33.5 ± 0.3, 33.9 ± 0.3, 33.9 ± 0.3, 33.5 ± 0.4°C). All patients recovered from the epidural anesthesia satisfactorily and without residual sequelae.
|
Discussion
|
|---|
The results of the repeated-measures ANOVAs were confounded because some patients were "rescued" with ephedrine to treat hypotension. Such rescues should bias the repeated-measures results against finding differences in MAP among the treatment groups. Thus, the true MAP differences among the treatment groups may be even greater than reported. The overall result showed the effectiveness of 200 µg of epidural PHE in maintaining MAP. The HR results should also be viewed in light of possible confounding by ephedrine use. Although more patients in Groups 1 and 2 than in Groups 3 and 4 received ephedrine rescue, we did not see a positive chronotropic effect of ephedrine (Figure 2). Perhaps the chronotropic effect of our ephedrine rescue was transient and not evident at the 5-min monitoring interval in this study.
Epidural anesthesia causes hypotension by sympathetic blockade and its associated vasodilation. Hypotension can be prevented or treated by the IV administration of crystalloid solution (2) or sympathomimetics, such as ephedrine. However, large fluid loads may be poorly tolerated by patients with limited myocardial reserve or with a relatively fixed cardiac output because of valvular heart disease (2). The use of ephedrine may be associated with tachycardia through its ß-adrenergic effect, and myocardial irritability may produce arrhythmias (2). PHE, a pure 1-agonist, can also be used IV to treat epidural anesthesia-induced hypotension (1,2).
Goertz et al. (7) have shown that, with a central venous injection of 1 µg/kg PHE, there is an approximately 20% increase in MAP, and the peak effect was seen between 30 and 45 s. The duration of action of an IV bolus of PHE was reported to be 2–5 min (2). Stanton-Hicks et al. (3) showed that the onset of hemodynamic effects with epidural PHE begins at 5 min and reaches a maximal effect at 15 min with a duration of action of approximately 60 min. Until now, there has been no report regarding the anti-hypotensive effect of intrathecal PHE. We propose that PHE exerts its 1-vasoconstricting effect through epidural absorption into systemic circulation. Because epidural lidocaine-induced vasodilation and hypotension develop gradually, the vasopressor effect of epidural PHE might match the onset and duration of this effect better than the IV bolus of PHE, which has a quick onset but short duration of action.
The effect of IV or epidural PHE on cardiac output, stroke volume, and other hemodynamic variables varies with different dosages, as reported in different studies. Ramanathan and Grant (1) reported that IV PHE in 100-µg increments corrected maternal hypotension in epidural anesthesia for cesarean section and restored ventricular stroke volume, end-diastolic volume, and cardiac output to near baseline values. In a study in volunteers by Stanton-Hicks et al. (3), the use of 50 µg/mL epidural PHE (total dose 900-1100 µg) with lidocaine epidural block produced an increase in peripheral resistance and increased BP, but this resulted in a reduction in cardiac output and an increase in central venous pressure.
In our study, utilizing the 1-vasopressor effect of epidural PHE to counteract epidural lidocaine-induced hypotension, the amount of prehydration was reduced to 500 mL of crystalloid solution, which is less than the usual amount of 
1000 mL reported by others (2,8,9). The use of ephedrine was also reduced in both frequency and total dosage (Table 2). More patients in Groups 1 and 2 (Table 2) received IV ephedrine to prevent a further decrease of BP, which explains the increase of BP after 15–20 min with these two groups (Fig. 1). An IV PHE infusion has also been used to correct hypotension associated with epidural anesthesia (10). Based on the present study, epidural PHE has the advantage that it can be used to prevent epidural anesthesia-induced hypotension.
During lumbar epidural anesthesia, there is a compensatory vasoconstriction in the upper limbs (11). Thus, the addition of PHE in our study might further aggravate this vasoconstriction, which may, in turn, increase cardiac afterload and impose additional risks for patients with ischemic heart disease. Vickers et al. (10) suggested that the use of PHE should be avoided in patients with ischemic heart disease or hypertension. Goertz et al. (7) found transient impairment of left ventricular function in patients receiving a central venous injection of 1 µg/kg PHE for correcting hypotension during thoracic epidural anesthesia combined with general anesthesia. They suggested that pure vasopressor drugs should be avoided in patients whose cardiac sympathetic tone is reduced by high thoracic epidural block because left ventricular contractility is reduced as a result of cardiac sympathetic block, and drugs with mixed - and ß-agonistic properties may be more appropriate for this group of patients.
In the present study, skin temperature measurements in the foot yielded no evidence for PHE-induced vasoconstriction in the foot. There are several possible reasons for this. First, PHE-induced vasoconstriction primarily occurs in the upper extremities and trunk, not in the lower extremities, according to Stanton-Hicks et al. (3). Second, PHE-induced vasoconstriction probably does not completely counterbalance the lidocaine-induced vasodilation in the lower extremities. Third, there might be a difference between superficial and deep foot vasculature in terms of the vasoconstriction response to PHE. Bengtsson et al. (12) have shown that intraindividual changes in skin temperature reflects changes in superficial skin blood flow poorly or not at all. They suggested that estimation of skin blood flow by using laser Doppler flowmetry may be of greater value than temperature recording.
Regarding the safety of epidural PHE, Kozody et al. (13) reported that, in mongrel dogs, subarachnoid PHE 5 mg did not affect spinal cord blood flow, although regional dural vasoconstriction did occur. Intrathecal PHE 5 mg was used in tetracaine spinal anesthesia by Caldwell et al. (14), and no neurologic sequelae were reported. However, Sakura et al. (15) suggested that adding PHE 0.125% to tetracaine for spinal anesthesia increased the potential for transient neurologic symptoms. The concentrations used were much higher than that used in the present study. Stanton-Hicks et al. (3) reported no neurologic sequelae with the use of epidural PHE 1:20,000 with plain lidocaine in their study.
In conclusion, in this study, we showed that epidural PHE 10 µg/mL can effectively reduce the incidence of hypotension induced by the epidural administration of alkalinized lidocaine. However, no systemic studies on the pharmacokinetics and safety of epidural PHE have been performed, and its use should be considered investigational.
|
Acknowledgments
|
|---|
We thank all the nurse anesthetists in our department for their assistance in collecting data; Mr. Paul C. Huang and Mr. Robert James for statistic analysis; and Dr. Hui-Lin Pan and Dr. James C. Eisenach for their reviews of the manuscript.
|
References
|
|---|
-
Ramanathan S, Grant GJ. Vasopressor therapy for hypotension due to epidural anesthesia for cesarean section. Acta Anaesthesiol Scand 1988;32:559–65.[ISI][Medline]
-
Morgan P. The role of vasopressors in the management of hypotension induced by spinal and epidural anaesthesia. Can J Anaesth 1994;41:404–13.[Abstract/Free Full Text]
-
Stanton-Hicks M, Berges PU, Bonica JJ. Circulatory effects of peridural block. IV. Comparison of the effects of epinephrine and phenylephrine. Anesthesiology 1973;39:308–14.[ISI][Medline]
-
Fernando R, Jones HM. Comparison of plain alkalinized local anaesthetic mixtures of lidocaine and bupivacaine for elective extradural caesarean section. Anaesth 1991;67:699–703.
-
Capogna G, Celleno D, Costantino P, et al. Alkalinization improves the quality of lidocaine-fentanyl epidural anaesthesia for caesarean section. Can J Anaesth 1993;40:425–30.
-
Benzon HT, Toleikis JR, Dixit P, et al. Onset, intensity of blockade and somatosensory evoked potential changes of the lumbosacral dermatomes after epidural anesthesia with alkalinized lidocaine. Anesth Analg 1993;76:328–32.[ISI][Medline]
-
Goertz AW, Seeling W, Heinrich H, et al. Effect of phenylephrine bolus administration on left ventricular function during high thoracic and lumbar epidural anesthesia combined with general anesthesia. Anesth Analg 1993;76:541–5.[Abstract/Free Full Text]
-
Halpern S, Glanc P, Myhr T, et al. Uterine and umbilical blood flow velocity during epidural anaesthesia for Caesarean section. Can J Anaesth 1994;41:1057–62.[Abstract/Free Full Text]
-
Fong J, Gurewitsch ED, Press RA, et al. Prevention of maternal hypotension by epidural administration of ephedrine sulfate during lumbar epidural anesthesia for cesarean section. Am J Obst Gynecol 1996;175:985–90.[ISI][Medline]
-
Vickers MD, Morgan M, Spencer PSJ. Drugs in anaesthetic practice. 7th ed.Oxford:Butterworth–Heinemann, 1991:301–53.
-
Baron JF, Payen D, Coriat P, et al. Forearm vascular tone and reactivity during lumbar epidural anesthesia. Anesth Analg 1988;67:1065–70.[ISI][Medline]
-
Bengtsson M, Nilsson GE, Lofstrom JB. The effect of spinal analgesia on skin blood flow, evaluated by laser Doppler flowmetry. Acta Anaesthesiol Scand 1983;27:206–10.[ISI][Medline]
-
Kozody R, Palahniuk RJ, Wade JG, et al. The effect of subarachnoid epinephrine and phenylephrine on spinal cord blood flow. Anaesth Soc J 1984;31:503–8.
-
Caldwell C, Nielsen C, Baltz T, et al. Comparison of high-dose epinephrine and phenylephrine in spinal anesthesia with tetracaine. Anesthesiology 1985;62:804–7.[ISI][Medline]
-
Sakura S, Sumi M, Sakaguchi Y, et al. The addition of phenylephrine contributes to the development of transient neurologic symptoms after spinal anesthesia with 0.5% tetracaine. Anesthesiology 1997;87:771–8.[ISI][Medline]
Accepted for publication February 22, 1999.
Top
Abstract
Introduction
