Anesth Analg 2003;96:1042-1046
© 2003 International Anesthesia Research Society
ANESTHETIC PHARMACOLOGY
The Dose Effect of Ephedrine on the Onset Time of Vecuronium
Kyo S. Kim, MD PhD,
Mi A. Cheong, MD,
Jeong W. Jeon, MD,
Jeong H. Lee, MD, and
Jae C. Shim, MD PhD
Department of Anesthesiology, Hanyang University Hospital, Seoul, Korea
Address correspondence and reprint requests to Kyo Sang Kim, MD, PhD, Department of Anesthesiology, Hanyang University Hospital, #17 Haengdang dong, Sungdong gu, Seoul 133-792, Korea. Address e-mail to kimks{at}hanyang.ac.kr
 |
Abstract
|
|---|
A small dose of ephedrine decreases the onset time of rocuronium and cisatracurium; however, ephedrine might be associated with adverse hemodynamic effects. The appropriate dose of ephedrine has not been determined. We, therefore, studied 120 patients anesthetized with fentanyl 2 µg/kg and propofol 2–2.5 mg/kg who were randomly divided to receive either ephedrine (30, 70, or 110 µg/kg) or saline. During propofol anesthesia, the neuromuscular block was monitored by mechanomyography by using submaximal current of train-of-four stimulation every 10 s. To determine cardiac output, a transcutaneous Doppler probe was placed externally at the suprasternal notch. Tracheal intubation was performed by a blinded investigator at 2 min after vecuronium. Neuromuscular block, intubating conditions, and hemodynamic effects were measured during the induction of anesthesia. Both ephedrine 70 and 110 µg/kg improved intubating conditions at 2 min after vecuronium; however, 110 µg/kg was associated with adverse hemodynamic effects. We conclude that ephedrine 70 µg/kg given before the induction of anesthesia improved intubating conditions at 2 min after vecuronium, probably by increased cardiac output without significant adverse hemodynamic effects.
IMPLICATIONS:Ephedrine 70 µg/kg given before the induction of anesthesia improved tracheal intubating conditions at 2 min after vecuronium by increased cardiac output without significant adverse hemodynamic effects.
|
Introduction
|
|---|
A small dose (70 µg/kg) of ephedrine administered with the induction of anesthesia reduced the onset time of rocuronium by 22%–26% (1,2) . However, in many countries, the use of rocuronium may be limited to the induction of anesthesia because of its expense. Although vecuronium has many desirable characteristics (3), its onset time is more than 3 min at a dose of 0.1 mg/kg and is much slower compared with rocuronium (4). The techniques to decrease the onset time of nondepolarizing neuromuscular blocking drugs have included the use of a priming dose before the administration of the intubating dose (5), increments in the dose (6), and a combination of drugs (7).
Both tachycardia and hypertension are not present even when 10 mg of IV ephedrine is given simultaneously with the dosing of spinal anesthesia (8). However, tachycardia and hypertension are associated with laryngoscopy and tracheal intubation (9). When pretreatment of ephedrine is given before tracheal intubation, we should consider the adverse effects of ephedrine. Therefore, the addition of ephedrine should be assessed by choosing the appropriate dose and by considering the adverse hemodynamic effects during the induction of anesthesia.
The aim of this study was to evaluate the dose of ephedrine suitable to reduce the onset time of neuromuscular block as regards blood pressure, heart rate, cardiac output, systemic vascular resistance (SVR), evolution during the anesthetic induction sequence, and the intubating conditions at 2 min after the administration of vecuronium 0.1 mg/kg.
|
Methods
|
|---|
After obtaining Hospital Ethics Committee approval and informed consent, we studied 120 patients, ASA status I or II, aged 20–57 yr, undergoing elective surgical procedures. No patient had any disease or metabolic abnormality known to alter neuromuscular transmission or was receiving any drug known or suspected to interfere with neuromuscular function. In addition to standard monitoring, cardiac output and SVR were monitored. To measure cardiac output, a transcutaneous Doppler probe (Accucom 2; Datascope Co., Paramus, NJ) was placed externally at the suprasternal notch (10). To observe optimal values, a digital measure of received Doppler signal strength was continuously noted, and the lower quality (<90) of values was excluded. These values represented the average measurements over a 15-s interval. Patients without premedication were randomly assigned to receive, in 5 s, saline (placebo; n = 30), 30 µg/kg of ephedrine (E30; n = 30), 70 µg/kg of ephedrine (E70; n = 30), or 110 µg/kg of ephedrine (E110; n = 30) 30 s before the administration of propofol.
The anesthesiologist performing the induction of anesthesia was blinded to the study doses of the drug (ephedrine or saline). Anesthesia was induced with fentanyl 2 µg/kg and the study drug, followed 30 s later by propofol 2–2.5 mg/kg over 30 s with 50% nitrous oxide in oxygen. After loss of the eyelash reflex and confirmation that ventilation via a face mask was possible, vecuronium 0.1 mg/kg was administered in 5 s. Tracheal intubation at 2 min after vecuronium injection was performed by a skilled anesthesiologist blinded to group assignment within <15 s. After the preliminary study, we chose 2 min as the time of the tracheal intubation. Intubating conditions were rated by the intubator as excellent, good, poor, or impossible (11). After the position of the endotracheal tube was confirmed, positive pressure ventilation was started and maintained with intermittent fentanyl 1–2 µg/kg, a continuous infusion of propofol 8–10 mg · kg-1 · h-1, and 70% nitrous oxide in oxygen. Ventilation was adjusted to maintain normocapnia (end-tidal carbon dioxide partial pressure 35–40 mm Hg).
The neuromuscular blockade monitoring was started 2 min before the administration of the study drug on the arm contralateral to the IV line by using a Myotest DBS peripheral nerve stimulator (Biometer Co., Odense, Denmark) of the adductor pollicis to a train-of-four (TOF) stimulation at 10-s intervals with submaximal current (20 mA). The resultant contraction was recorded with a force displacement transducer and a neuromuscular function analyzer (Myograph 2000; Biometer Co.). Preload tension of the thumb was maintained at 300 g throughout the investigation. The onset time was defined as the time from the end of injection of vecuronium to maximum depression of the first twitch of TOF stimulation. The degree of neuromuscular block at the time of intubation was measured as the twitch depression of control first twitch of TOF stimulation, expressed as percentage. The palm skin temperature of the hand, where neuromuscular function was monitored, was maintained at more than 33°C.
Heart rate, mean arterial blood pressure (MAP), cardiac output, and SVR were measured just before induction, before intubation, and 1, 2, and 3 min after tracheal intubation. The adverse effect was defined as more than a 20% increase from the control value. The presence of arrhythmias on the electrocardiogram monitor was noted.
Statistical intragroup analysis was performed on raw data by using one-way analysis of variance, followed by post hoc Newman-Keuls tests for comparison with baseline. Comparison among groups was determined with two-way analysis of variance for repeated measurements and the Mann-Whitney U-test. The intubating conditions were analyzed by the Kruskal-Wallis measurement and the Tukey test. Differences were considered significant when P < 0.05. Values are reported as mean ± SD.
|
Results
|
|---|
No differences in patient characteristics or induction doses of fentanyl and propofol were found among groups (Table 1). One patient in the placebo group was excluded from the trial because of difficulty with tracheal intubation (laryngoscopic grade IV). No additional doses of fentanyl or propofol were given during the study period.
The endotracheal intubating conditions at 2 min after vecuronium are shown in Table 2. The frequency of acceptable intubating conditions (excellent and good) was significantly increased after larger ephedrine doses (E70 and E110; 93% and 97%) than placebo (52%) (P < 0.001), but there were no differences among dosages of ephedrine. At the time of intubation, neuromuscular block was more intense in patients receiving larger doses of ephedrine (E70 and E110) than placebo (P < 0.05). The onset time of vecuronium was also shorter after larger doses of ephedrine (E70 and E110) than placebo (P < 0.05) (Table 3).
View this table:
[in this window]
[in a new window]
|
Table 3. Neuromuscular Block (% Twitch Depression of Control First Twitch of TOF Stimulation) at Intubation and Onset Time of Vecuronium
|
|
Multiple comparisons with regard to MAP (Fig. 1) and heart rate (Fig. 2) among groups at individual time points demonstrated significant differences between the placebo and ephedrine groups at preintubation and between the E110 group and other groups at 1 min after tracheal intubation (P < 0.001). One (3%) patient in the E30 group and 16 (55%) patients in the placebo group at preintubation (P < 0.001) experienced a decrease in systolic arterial blood pressure to <80 mm Hg. The incidence of extreme changes (>30% from baseline) of MAP in E110 was 87%, whereas it was <10% in the other groups at 1 min after tracheal intubation (P < 0.001). Six patients in E110 experienced marked tachycardia (>130 bpm for <5 s) at 1 min after tracheal intubation. No patient presented arrhythmias during the study period.
View larger version (14K):
[in this window]
[in a new window]
|
Figure 1. Changes in mean arterial blood pressure in each group (n = 30) during induction. Values are mean ± SD. Placebo = saline; E30 = ephedrine 30 µg/kg; E70 = ephedrine 70 µg/kg; E110 = ephedrine 110 µg/kg. *P < 0.001 versus ephedrine groups. +P < 0.001 versus other groups.
|
|
View larger version (12K):
[in this window]
[in a new window]
|
Figure 2. Changes in heart rate in each group (n = 30) during induction. Values are mean ± SD. Placebo = saline; E30 = ephedrine 30 µg/kg; E70 = ephedrine 70 µg/kg; E110 = ephedrine 110 µg/kg. *P < 0.001 versus ephedrine groups. +P < 0.001 versus other groups.
|
|
Cardiac index (CI) (Fig. 3) and SVR (Fig. 4) after saline were decreased after induction with propofol (P < 0.001), but not after ephedrine. CI and SVR were greater in the ephedrine groups at 1 min after tracheal intubation compared with placebo (P < 0.001). CI was correlated with the onset time of vecuronium in both the E70 and E110 groups (P < 0.001). Three minutes after tracheal intubation, CI and SVR returned to baseline in all groups. There were no arrhythmias after pretreatment of ephedrine during the induction of anesthesia.
View larger version (13K):
[in this window]
[in a new window]
|
Figure 3. Changes in cardiac index in each group (n = 30) during induction. Values are mean ± SD. Placebo = saline; E30 = ephedrine 30 µg/kg; E70 = ephedrine 70 µg/kg; E110 = ephedrine 110 µg/kg. *P < 0.001 versus ephedrine groups.
|
|
View larger version (13K):
[in this window]
[in a new window]
|
Figure 4. Changes in systemic vascular resistance (SVR) in each group (n = 30) during induction. Values are mean ± SD. Placebo = saline; E30 = ephedrine 30 µg/kg; E70 = ephedrine 70 µg/kg; E110 = ephedrine 110 µg/kg. *P < 0.001 versus ephedrine groups.
|
|
|
Discussion
|
|---|
The main finding of this study was that both ephedrine 70 and 110 µg/kg could improve intubating conditions two minutes after vecuronium; however, 110 µg/kg was associated with adverse hemodynamic effects. The rapid onset of vecuronium was attributed to an increased cardiac output.
Previous studies with vecuronium have demonstrated a significant reduction in onset time with the use of a priming dose before the administration of the intubating dose (5) and increased dose (6). Although these alternatives could reduce the onset time of vecuronium, some could also lead to adverse effects, such as the development of muscle weakness, loss of airway control (12), or increased duration of neuromuscular blockade (4). Ephedrine 70 µg/kg reduced the onset time of rocuronium from 98 to 72 seconds (2) and reduced that of cisatracurium from 234.9 to 167 seconds (13). We suspect that pretreatment with ephedrine 70 µg/kg reduced the onset time of vecuronium by 23%, was equally as effective as priming with vecuronium 0.01 mg/kg, and was certainly safer. We also suspect that pretreatment with ephedrine is applicable to other competitive antagonists to reduce the onset time.
Ephedrine in doses of 70, 140, 210, and 280 µg/kg is very effective at obtunding the hypotensive response to propofol (14,15) . Marked tachycardia and hypertension associated with the use of ephedrine in combination with propofol after tracheal intubation occurred in most patients. Because of the risk of this tachycardia-inducing myocardial ischemia, the use of any of the ephedrine/propofol mixtures is not recommended for elderly patients (16). We also found that ephedrine 110 µg/kg was associated with marked hypertension and tachycardia (30% and 32% more than control, respectively) at one minute after intubation. However, ephedrine 30 µg/kg maintained stable hemodynamic values during induction with poor intubating conditions (17%). An appropriate dose of ephedrine (70 µg/kg) should be used to minimize the adverse effects and reduce the onset time of vecuronium.
The initial arterial concentrations of propofol after IV administration are inversely related to cardiac output. This implies that cardiac output may be a determinant of the induction of anesthesia with propofol (17). The decrease in cardiac output frequently observed after propofol administration was due to the myocardial depression (18). We also found the corresponding decrease in CI, from 3.1 to 2.3 L · min-1 · m-2, and confirmed the vasodilator effect of propofol in decreasing SVR from 2417 to 1894 dynes · s · cm-5. However, CI was not decreased after tracheal intubation. A possible explanation is that the concomitant increase in the plasma catecholamine concentrations was due to laryngoscopy and tracheal intubation (19), and inhaled anesthetic was not required for the anesthesia in this study.
The continuous-wave transesophageal Doppler device for cardiac output monitoring (Accucom 2) is reproducible, showing less short-term variability than thermodilution cardiac output. The suprasternal Doppler technique has shown promise for measuring cardiac output and SVR noninvasively (10). It is highly correlated with the results obtained with thermodilution (r = 0.91–0.95) (20). Accucom 2, provided that the aortic blood flow velocity signal is stable and free from any disturbances, may be regarded as acceptable for cardiac output trend monitoring in sedated, paralyzed patients (21). However, limitations of transesophageal Doppler monitoring—including a difficult calibration procedure, poor performance during aortic cross-clamping, and the need for probe repositioning—suggest that further development is warranted (22).
Neuromuscular testing in awake patients is further limited by patient discomfort. The use of less painful, submaximal stimulating currents may facilitate neuromuscular monitoring (23). TOF ratios obtained at submaximal current correlate highly with those at supramaximal current (24). The reliability of submaximal current at 20 mA suggests that one could deliberately use such a low amperage for evaluating the degree of neuromuscular block in awake patients (25). Therefore, we chose a submaximal current (20 mA). However, a limitation of the current study may be the comparison of the first twitch of TOF stimulation due to the submaximal response of the twitch height.
Although we did not find severe adverse effects after the administration of ephedrine in relative healthy patients, we should consider that the incidence of adverse effects might be more frequent in patients with cardiovascular disease or with use of a different induction technique (15).
In conclusion, ephedrine 70 µg/kg given before the induction of anesthesia improved intubating conditions at 2 min after vecuronium by increased cardiac output without significant adverse hemodynamic effects.
|
References
|
|---|
- Szmuk P, Ezri T, Chelly JE, Katz J. The onset time of rocuronium is slowed by esmolol and accelerated by ephedrine. Anesth Analg 2000; 90: 1217–9.[Abstract/Free Full Text]
- Munoz HR, Gonzalez AG, Dagnino JA, et al. The effect of ephedrine on the onset time of rocuronium. Anesth Analg 1997; 85: 437–40.[ISI][Medline]
- Magorian T, Flannery KB, Miller RD. Comparison of rocuronium, succinylcholine, and vecuronium for rapid-sequence induction of anesthesia in adult patients. Anesthesiology 1993; 79: 913–8.[ISI][Medline]
- Tullock WC, Diana P, Cook DR, et al. Neuromuscular and cardiovascular effects of high-dose vecuronium. Anesth Analg 1990; 70: 86–90.[Abstract/Free Full Text]
- Schwarz S, Ilias W, Lackner F, et al. Rapid tracheal intubation with vecuronium: the priming principle. Anesthesiology 1985; 62: 388–91.[ISI][Medline]
- Rorvik K, Husby P, Gramstad L, et al. Comparison of large dose of vecuronium with pancuronium for prolonged neuromuscular blockade. Br J Anaesth 1988; 61: 180–5.[Abstract/Free Full Text]
- Naguib M. Different priming techniques, including mivacurium, accelerate the onset of rocuronium. Can J Anaesth 1994; 41: 902–7.[Abstract/Free Full Text]
- Tsen LC, Boosalis P, Segal S, et al. Hemodynamic effects of simultaneous administration of intravenous ephedrine and spinal anesthesia for cesarean delivery. J Clin Anesth 2000; 12: 378–82.[ISI][Medline]
- Horak J, Weiss S. Emergent management of the airway: new pharmacology and the control of comorbidities in cardiac disease, ischemia, and valvular heart disease. Crit Care Clin 2000; 16: 411–27.[ISI][Medline]
- Freund PR. Transesophageal Doppler scanning versus thermodilution during general anesthesia: an initial comparison of cardiac output techniques. Am J Surg 1987; 153: 490–4.[ISI][Medline]
- Cooper R, Mirakhur RK, Clarke RS, Boules Z. Comparison of intubating conditions after administration of Org 9246 (rocuronium) and suxamethonium. Br J Anaesth 1992; 69: 269–73.[Abstract/Free Full Text]
- Jones RM. The priming principle: how does it work and should we be using it? Br J Anaesth 1989; 63: 1–3.[Free Full Text]
- Albert F, Hans P, Bitar Y, et al. Effects of ephedrine on the onset time of neuromuscular block and intubating conditions after cisatracurium: preliminary results. Acta Anaesthesiol Belg 2000; 51: 167–71.[Medline]
- Gamlin F, Vucevic M, Winslow L, Berridge J. The haemodynamic effects of propofol in combination with ephedrine. Anaesthesia 1996; 51: 488–91.[ISI][Medline]
- el-Beheiry H, Kim J, Milne B, Seegobin R. Prophylaxis against the systemic hypotension induced by propofol during rapid-sequence intubation. Can J Anaesth 1995; 42: 875–8.[Abstract/Free Full Text]
- Gamlin F, Freeman J, Winslow L, et al. The haemodynamic effects of propofol in combination with ephedrine in elderly patients (ASA groups 3 and 4). Anaesth Intensive Care 1999; 27: 477–80.[ISI][Medline]
- Upton RN, Ludbrook GL, Grant C, Martinez AM. Cardiac output is a determinant of the initial concentrations of propofol after short-infusion administration. Anesth Analg 1999; 89: 545–52.[Abstract/Free Full Text]
- Park WK, Lynch C III. Propofol and thiopental depression of myocardial contractility: a comparative study of mechanical and electrophysiologic effects in isolated guinea pig ventricular muscle. Anesth Analg 1992; 74: 395–405.[Abstract/Free Full Text]
- Derbyshire DR, Chmielewski A, Fell D, et al. Plasma catecholamine response to tracheal intubation. Br J Anaesth 1983; 55: 855–60.[Abstract/Free Full Text]
- Perrino AC Jr, Fleming J, LaMantia KR. Transesophageal Doppler ultrasonography: evidence for improved cardiac output monitoring. Anesth Analg 1990; 71: 651–7.[Abstract/Free Full Text]
- Schmid ER, Spahn DR, Tornic M. Reliability of a new generation transesophageal Doppler device for cardiac output monitoring. Anesth Analg 1993; 77: 971–9.[Abstract/Free Full Text]
- Perrino AC Jr, Fleming J, LaMantia KR. Transesophageal Doppler cardiac output monitoring: performance during aortic reconstructive surgery. Anesth Analg 1991; 73: 705–10.[Abstract/Free Full Text]
- Connelly NR, Silverman DG, O’Connor TZ, Brull SJ. Subjective responses to train-of-four and double burst stimulation in awake patients. Anesth Analg 1990; 70: 650–3.[Abstract/Free Full Text]
- Silverman DG, Connelly NR, O’Connor TZ, et al. Accelographic train-of-four at near-threshold currents. Anesthesiology 1992; 76: 34–8.[ISI][Medline]
- Brull SJ, Ehrenwerth J, Silverman DG. Stimulation with submaximal current for train-of-four monitoring. Anesthesiology 1990; 72: 629–32.[ISI][Medline]
Accepted for publication August 7, 2002.
This article has been cited by other articles:
|
|
|
|
 
T. M. Hemmerling, G. Michaud, S. Deschamps, G. Trager, and K. S. Kim
Do We Need to Intubate the Trachea 2 Minutes after Vecuronium 0.1 mg/kg in Elective Surgery? * Response
Anesth. Analg.,
November 1, 2003;
97(5):
1544 - 1545.
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
