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From the Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, Peoples Republic of China.
Dr K.S. Khaw. Phone: +852-2632-2735; Fax: +852-2637-2422; E-mail: kimkhaw{at}cuhk.edu.hk
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Abstract |
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Methods: A lumbar epidural catheter was inserted and patients lay in the supine left wedge position. Intravenous fluid preload was withheld, and hemodynamic measurements comprising of mean arterial pressure, cardiac output and heart rate were made using automatic oscillotonometry (Dinamap 1486SX) and transthoracic electrical bioimpedance (Bomed NCCOM3). Following baseline measurements, the hemodynamic effects of sequential epidural injection of first, 10 ml saline, and 20 min thereafter, 50 mg meperidine diluted to 10 ml with saline, were recorded. Sensory blockade was assessed following each injection using loss of temperature discrimination to ice. Paired Student t tests were used to compare changes in hemodynamic variables.
Results: Epidural meperidine produced a small increase from the saline values in the mean (SD) cardiac output of 5.81 ±1.44 to 6.04 ± 1.54 L
min–1 (P < 0.05), and mean arterial pressure of 77.1 ± 8.8 to 79.3 ± 9.9 mmHg (P < 0.05). Sensory changes, the upper level of which ranged from L1 to T1, were detected in 94% of patients given epidural meperidine. Epidural saline injection had no such hemodynamic effects, but produced a detectable sensory level in two patients.
Conclusion: Epidural meperidine, 50 mg, caused minimal hemodynamic changes in term parturients.
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Introduction |
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We have previously shown that intrathecal meperidine caused hypotension and bradycardia that were equivalent to, or greater than, those seen with heavy bupivacaine 0.5%.5 Whether similar hemodynamic effects occur following epidural administration of meperidine has not been previously described. Thus, the purpose of this study was to determine whether an analgesic dose of epidural meperidine (50 mg) causes hemodynamic effects in non-labouring term parturients.
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Methods |
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Mean arterial pressures (MAP) were measured at two-minute intervals using an automated oscillotonometer (Dinamap 1846SX, Critikon, Florida, USA) and data were recorded on an integral printer. Cardiac output (CO) and heart rate (HR) were measured continuously using the BoMed NCCOM3-R7S (BoMed Manufacturing, Irvine, CA, USA) and these data were uploaded to a laptop computer, as described in previous studies.5,8,9 The BoMed NCCOM3 was connected to the patient using an eight electrode montage to the neck and lower thorax.10 Fetal well being was continuously monitored using a cardiotocograph, and regularly assessed by a midwife present for the duration of the study.
Following a 10 min stabilisation period, baseline hemodynamic data were collected over 20 min. Ten millitres of normal saline (placebo) were then injected epidurally over 30 sec and hemodynamic variables were recorded for a further 20 min. Following this, 50 mg meperidine (Antigen Pharmaceuticals Ltd., Roscrea, Ireland) diluted to 10 ml with normal saline was injected epidurally, and hemodynamic variables were measured for a further 20 min. Thus, three sets of hemodynamic monitoring data were obtained from each patient. The presence of sensory blockade was assessed at 20 min intervals following each epidural injection using loss of temperature discrimination to ice in the midline.
Our protocol for treatment of hypotension, defined as a decrease in MAP of > 25% from baseline, was a rapid infusion of 15 mlkg–1 Ringer's lactate solution and boluses of 6 mg ephedrine iv. Nausea and vomiting were treated with 10 mg metoclopramide iv, once hypotension had been excluded. After data collection was completed, the patient was prepared for Cesarean section by extending the epidural block to the appropriate level using lidocaine 2% with 1:200000 adrenaline.
Statistical analysis was performed using the programme Statview 4.5 (Abacus Concepts, Inc., Berkeley, CA, USA). Hemodynamic data were analysed using methods similar to those used in our previous studies of hemodynamic changes associated with spinal anesthesia.5,8,9 The BoMed produced a cardiac output and heart rate measurement every 16 heartbeats, and these were averaged to produce mean values for each two-minute time period. To allow time for the hemodynamic changes associated with epidural meperidine to become established, only data collected during the second half (10 min), following each epidural injection were analysed. In each patient, "typical" mean values for cardiac output, heart rate and mean arterial pressure were calculated by averaging data collected during each of the three 10–20 min time periods. Paired Students t tests (two tailed) were used to compare hemodynamic variables from each study period. P < 0.05 was considered significant.
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Results |
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Hemodynamic variables recorded during the study are plotted in Figure
. Results after analysis are presented as mean ± SD in the Table . The mean value of hemodynamic variables at baseline, and at 10-20 min following epidural injection with normal saline (placebo) and meperidine are shown. Cardiac output increased by 0.23 ± lmin–1 (3.9%,) (P < 0.05) and MAP increased by 2.2 ± mmHg (3.0%) (P < 0.05) after the injection of meperidine. All patients proceeded uneventfully to Cesarean section. No interventions were required for hypotension or nausea and vomiting, and no adverse maternal side effects, or fetal cardiotocograph changes were encountered during the study.
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Discussion |
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min–1 (3.9%) and MAP increased by 2.2 mmHg (3.0%), 10 min after injection of epidural meperidine but these increases were not accompanied by any changes in heart rate. Although the cardiac output and MAP increases were significant statistically, the magnitude of change was small and thus unlikely to be of clinical importance. This is in agreement with a previous study in which we investigated epidural meperidine in doses up to 100 mg for analgesia after Cesarean section and found no clinically important changes in arterial pressure or heart rate.11 However, in that study the patients were studied in the early postoperative phase, and the administration of peri-operative fluids and the persisting effects of epidural local anesthetic made it difficult to clearly exclude any hemodynamic effects of epidural meperidine. In this study, fluid administration was withheld, and no other drugs were administered epidurally other than the study drug, thus allowing more subtle changes in hemodynamic status to be detected.
We chose to investigate a dose of 50 mg epidural meperidine as this dose has previously been described for intraoperative analgesia during Cesarean section under epidural anesthesia.12 In our unit, we commonly use this dose intra-operatively to supplement local anesthesia, followed by a smaller dose (25 mg) for postoperative analgesia. For the purpose of this study, meperidine was given earlier, before giving the local anesthetic. When used for patient controlled epidural analgesia after Cesarean section and other surgery, meperidine has compared favourably with fentanyl13,14 and local anesthetic-opioid combinations.15 In our own previous study, we found that a dose of 25 mg was the optimum for postoperative analgesia use.11
At higher doses (2.6-3.8 mgkg–1), surgical anesthesia can be obtained by using only epidural meperidine. However, at this dose, epidural meperidine can have clinically significant hemodynamic effects as well as causing drowsiness and hypoventilation.16 There are no published reports of such high doses used in obstetric anesthesia. Concern for systemic absorption, and transplacental transfer of meperidine may be a factor precluding the use of such high doses.
Several mechanisms can be postulated for our present hemodynamic findings. In most patients, there was evidence of sensory block, which would also have been associated with some degree of sympathetic block. This would result in vasodilatation and the accompanying reduction in afterload would account for the small increase in the stroke volume and hence cardiac output.17 However, this mechanism does not account for the increase in arterial blood pressure, which would imply that the contractility of the heart had also increased. Although it is possible that systemic absorption of meperidine may have contributed to such hemodynamic changes either by acting centrally or by direct vasodilatation, we have previously found that plasma concentrations of meperidine were relatively low (median concentration 213 ngml–1) 20 min after epidural injection of 50 mg meperidine.11
Epidural meperidine resulted in sensory changes, with upper limits at T8 (L1-T2) in most of the patients (94%). We measured our sensory changes commencing from L5 but did not attempt to measure lower limits, as this would have interfered with the impedance cardiography monitoring. Saline was injected unknown to the patients, to exclude psychological factors, such as sensation of the epidural injection as a cause of the patient's hemodynamic changes. Interestingly, epidural saline also caused sensory blocks in two patients (up to T8 and L1), but without any accompanying hemodynamic changes. This unexpected finding has been previously reported by Hore et al., although the exact mechanism is uncertain.18 Although we did not formally test for motor block, as this would have interfered with the monitoring of hemodynamic variables, none of our patients complained of leg weakness during or at the completion of the study.
Both the Dinamap and BoMed are well-established devices for determining changes in hemodynamic variables in healthy adult subjects.19–22 During pregnancy, the Dinamap reportedly overestimates systolic arterial pressure, though the repeatability of its measurements is well maintained with confidence limits of ± 10%.19 Milson et al. compared the stroke volume from transthoracic electrical bioimpedance devices against dye dilution in late pregnancy, and showed that the method is a reliable trend monitor in this setting.21 As a prelude to our current study, we validated our use of the Dinamap and the BoMed in a group of 20 parturients requiring Cesarean section who were given lidocaine 2% with adrenaline 1:200,000. The Dinamap and BoMed were consistently able to detect the changes in cardiac output and arterial pressure that occur after the epidural injection (unpublished data).
In summary, we found that epidural meperidine 50 mg given to non-labouring term parturients produced small increases in hemodynamic variables that are unlikely to be of clinical importance. Although meperidine produces marked hemodynamic changes when given intrathecally for anesthesia, similar hemodynamic changes were not seen when meperidine was used for epidural analgesia.
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Acknowledgments |
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Accepted for publication October 15, 1999.
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References |
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2 Beyazova M, Babacan A, Bilir E, Akçabay M, Kaya K, Baysal AÎ. Perineural meperidine: effects of different doses on nerve conduction. Eur J Anaesthesiol 1993; 10: 353–6.[Medline]
3 Kaya K, Babacan A, Beyazova M, Bölükbasi N, Akçabay M, Karadenizli Y. Effects of perineural opioids on nerve conduction of N. suralis in man. Acta Neurol Scand 1992; 85: 337–9.[Medline]
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Acalovschi I, Ene V, Lörinczi E, Nicolaus F. Saddle block with pethidine for perineal operations. Br J Anaesth 1986; 58: 1012–6.
5
Conway F, Critchley LA, Stuart JC, Freebairn RC. A comparison of the haemodynamic effects of intrathecal meperidine, meperidine-bupivacaine mixture and hyperbaric bupivacaine. Can J Anaesth 1996; 43: 23–9.
6 Mircea N, Constantinescu C, Jianu E, et al. Spinal anesthesia with pethidine. Ann Fr Anesth Reanim 1982; 1: 167–71.[Medline]
7 Famewo CE, Naguib M. Spinal anaesthesia with meperidine as the sole agent. Can Anaesth Soc J 1985; 32: 533–7.[Medline]
8
Critchley LAH, Conway F. Hypotension during subarachnoid anaesthesia: haemodynamic effects of colloid and metaraminol. Br J Anaesth 1996; 76: 734–6.
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Critchley LAH, Stuart JC, Short TG, Gin T. Haemodynamic effects of subarachnoid block in elderly patients. Br J Anaesth 1994; 73: 464–70.
10 BoMed Ltd. Prepare the patient. In: BoMed Ltd. NCCOM3-R7S Cardiodynamic Monitor Operator's Manual. Irvine, CA: BoMed Ltd, 1991: 15–7.
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16
Kaza R, Lawlor M, Allen W, Ranella L, Johnson C. Epidural meperidine provides surgical anesthesia for critically ill patients undergoing major surgery. (Letter) Anesth Analg 1993; 77: 1084.
17 Guyton AC. Heart muscle; the heart as a pump. In: Guyton AC (Ed.). Textbook of Medical Physiology. Philadelphia: W.B. Saunders, 1991: 98–109.
18 Hore PJ, Silbert BS, Cook RJ, Beilby DSN. A double-blind assessment of segmental sensory changes with epidural fentanyl versus epidural saline in patients undergoing extracorporeal shock-wave lithotripsy. Anesthesiology 1990; 72: 603–6.[Medline]
19
Hasan MA, Thomas TA, Prys-Roberts C. Comparison of automatic oscillometric arterial pressure measurement with conventional auscultatory measurement in the labour ward. Br J Anaesth 1993; 70: 141–4.
20 Milsom I, Forssman L, Biber B, Dottori O, Sivertsson R. Measurement of cardiac stroke volume during cesarean section: a comparison between impedance cardiography and the dye dilution technique. Acta Anaesthesiol Scand 1983; 27: 421–6.[Medline]
21 Milsom I, Forssman L, Sivertsson R, Dottori O. Measurement of cardiac stroke volume by impedance cardiography in the last trimester of pregnancy. Acta Obstet Gynecol Scand 1983; 62: 473–9.[Medline]
22 Critchley LAH, Conway F, Anderson PJ, Tomlinson B, Critchley JAJH. Non-invasive continuous arterial pressure, heart rate and stroke volume measurements during graded head-up tilt in normal man. Clin Auton Res 1997; 7: 97–101.[Medline]
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