JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Tanaka, M. Articles by Nishikawa, T. Search for Related Content PubMed PubMed Citation Articles by Tanaka, M. Articles by Nishikawa, T.

---

PEDIATRIC ANESTHESIA

The Efficacy of a Simulated Intravascular Test Dose in Sevoflurane-Anesthetized Children: A Dose-Response Study

Department of Anesthesia, Akita University School of Medicine, Akita, Japan

Address correspondence and reprint requests to Makoto Tanaka, MD, Department of Anesthesia, Akita University School of Medicine, Hondo 1-1-1, Akita-shi, Akita-ken 010-8543, Japan. Address e-mail to mtanaka{at}med.akita-u.ac.jp

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
A recent study demonstrated that changes in both heart rate (HR; positive if 10 bpm increase) and T-wave amplitude (positive if 25% increase) reliably detect accidental intravascular injection when a full test dose containing epinephrine 0.5 µg/kg is injected intravascularly. We designed this study to prospectively determine whether a smaller dose of epinephrine would produce reliable HR and T-wave changes in sevoflurane-anesthetized children. We studied 80 ASA physical status I infants and children (6–72 mo) undergoing elective surgeries during 1.0 minimum alveolar anesthetic concentration sevoflurane and 67% nitrous oxide in oxygen. After the administration of IV atropine 0.01 mg/kg, the patients were randomly assigned to receive either IV saline (n = 20), an IV test dose (0.1 mL/kg) consisting of 1% lidocaine with 1:200,000 epinephrine (epinephrine 0.5 µg/kg group,

n = 20), an IV test dose (0.05 mL/kg) (epinephrine 0.25 µg/kg group, n = 20), or an IV test dose (0.025 mL/kg) (epinephrine 0.125 µg/kg group, n = 20) via a peripheral vein to simulate the intravascular injection of the test dose. HR and systolic blood pressure were recorded every 20 and 30 s, respectively, and T-wave amplitude of lead II was continuously recorded for subsequent analysis. After the IV injection of the test dose, all children in the epinephrine 0.5 and 0.25 µg/kg groups developed positive responses based on the peak T-wave amplitude, whereas all children in the epinephrine 0.5 µg/kg group and 17 children (85%) in the epinephrine 0.25 µg/kg group elicited a positive response according to the peak HR criterion. No false-positive responses were observed with saline injections. Children in the epinephrine 0.125 µg/kg group showed clinically unacceptable efficacy based on either criterion. We conclude that the efficacies of detecting an intravascular injection of the test dose based on the hemodynamic and T-wave criteria are reduced with smaller doses of epinephrine and that HR and T-wave changes are still useful indicators in most patients if epinephrine 0.25 µg/kg is accidentally injected intravascularly.

Implications: To determine whether an epidurally administered local anesthetic has been unintentionally injected into a blood vessel, a small dose of epinephrine is often added to a local anesthetic. We found that an increase in T-wave amplitude 25% in lead II and a heart rate increase 10 bpm are useful indicators for detecting the accidental intravascular injection of a small dose of epinephrine in sevoflurane-anesthetized children.

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Epidural anesthesia is often combined with general anesthesia and used for postoperative analgesia. In children, epidural anesthesia is often initiated under general anesthesia. To avoid life-threatening central nervous system and cardiac complications associated with a large amount of a local anesthetic solution being accidentally injected intravascularly (1), a small dose of epinephrine is added to local anesthetics. A peak heart rate (HR) increase 10 bpm is considered a reliable indicator of an intravascular injection in sevoflurane-anesthetized children (2), whereas systolic blood pressure (SBP) changes yield conflicting results (2–4).

Changes in T-wave amplitude in lead II electrocardiography (positive if 25% increase) have been suggested as just as reliable an indicator as the HR criterion when a full test dose containing 0.5 µg/kg epinephrine is injected IV (4,5). In clinical practice, however, only a fraction of the test dose may be administered intravascularly, and the potential usefulness of the T wave as a novel marker has not been determined using smaller doses of epinephrine. In addition, the minimal effective dose of the epinephrine-containing test dose to detect intravascular injection based on the conventional hemodynamic criteria has not been determined in anesthetized children. Accordingly, we designed the present prospective, randomized, dose-response study to determine hemodynamic responses to, and the efficacy of, three different doses of simulated IV test doses containing epinephrine based on the conventional hemodynamic and the more contemporary T-wave criteria in sevoflurane-anesthetized children.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
After institutional review board approval and informed, parental consent, 80 ASA physical status I children, aged 6–72 mo, with a normal sinus rhythm (determined by preoperative electrocardiography), undergoing elective minor surgeries under general anesthesia were enrolled. All patients were allowed ad libitum food 8 h before and a maximum of 10 mL/kg of clear liquid 4 h before the anticipated time of general anesthesia induction. They also received midazolam 1 mg/kg rectally 10 min before induction. A Jackson-Rees circuit was used with a fresh gas flow approximately 3 times the minute ventilation for children <15 kg, or semiclosed circle system with a fresh gas flow 6 L/min for children 15 kg was used throughout the study. Standard monitors, including an automated blood pressure (BP) cuff, electrocardiography (lead II), and a pulse oximeter, were applied. After mask induction with sevoflurane and 67% nitrous oxide in oxygen, a forearm peripheral vein was cannulated, and lactated Ringer's solution containing 2% dextrose was administered at a rate of 5 mL · kg^-1 · h^-1. Ventilation was first assisted, then controlled to obtain end-tidal CO₂ tensions between 30 and 35 mm Hg. Anesthesia was maintained with 1 minimum alveolar anesthetic concentration sevoflurane adjusted for age (6) and 67% nitrous oxide in oxygen. When hemodynamic variables and end-tidal concentrations were stable for at least 10 min after anesthetic induction, IV atropine 0.01 mg/kg was administered in all patients. Another 5 min was allowed to obtain a stable HR and SBP before patients were randomly assigned to one of the following groups according to computer-generated random numbers: an epinephrine 0.5 µg/kg group (n = 20) received a test dose consisting of 1% lidocaine with 1:200,000 epinephrine solution 0.1 mL/kg IV; an epinephrine 0.25 µg/kg group (n = 20) received the same test dose 0.05 mL/kg IV; an epinephrine 0.125 µg/kg group (n = 20) received the test dose 0.025 mL/kg IV; and the saline group (n = 20) received isotonic sodium chloride solution 0.1 mL/kg IV. The study solutions were prepared and coded by the hospital pharmacy and injected by a blinded observer (MT) over 5 s into a peripheral IV line before initiation of the surgery with the patient in the supine position. Measurements of HR and SBP were made at rest; after premedication with midazolam; at least 10 min after the induction of general anesthesia, before atropine administration, when stable hemodynamic variables and end-tidal concentrations were maintained; 5 min after the administration of IV atropine; and at 20-s (HR) and 30-s (SBP) intervals for 5 min after IV injections of the test dose or saline. Lead II was continuously recorded in a strip chart and subsequently analyzed for changes in T-wave amplitude before and after atropine administration, at its maximal amplitude, at the peak HR, and at 1-min intervals for 5 min after the test dose or saline injections. Arrhythmia, if present, was also noted. HR was computed using the mean of three consecutive RR intervals from the electrocardiography. BP was measured noninvasively throughout the study. All measurements of T-wave amplitude were made by another observer blinded to the treatment group of the patient and the hemodynamic changes.

A power analysis based on a previous report revealed that >16 patients would provide a power >0.8 (P = 0.05) for detection of a 25% difference in paired hemodynamic responses (7). Positive HR, SBP, and T-wave changes to IV test dose were prospectively defined from previous reports: positive if a HR increase 10 bpm, a SBP increase 15 mm Hg, and a T-wave increase 25% occurred within 2 min of administration (2,3,5). We determined sensitivity (true positives/[true positives + false negatives]), specificity (true negatives/[true negatives + false positives]), and positive (true positives/[true positives + false positives]) and negative predictive values (true negatives/[true negatives + false negatives]).

All values are presented as mean ± SD. Statistical analysis was performed by using two-way analysis of variance to compare changes in hemodynamic variables and T-wave amplitude among groups. When a significant difference was identified, it was followed by an unpaired Student's t-test with the Bonferroni correction. Intergroup differences in demographic data were also compared by using an unpaired Student's t-test with the Bonferroni correction or 2 test. Changes in hemodynamic variables and T-wave amplitudes over time within each group were analyzed by using repeated-measures analysis of variance, followed by a paired Student's t-test. Proportions of patients with positive responses were compared by using Fisher's exact probability test. A P value <0.05 was considered statistically significant.

	Results

Top Abstract Introduction Methods Results Discussion References

 
There were no significant differences in the patients' age, weight, height, and sex distribution among groups (Table 1). No hemodynamic changes occurred after the administration of rectal midazolam compared with resting values. After the induction of general anesthesia using sevoflurane and nitrous oxide, SBP and diastolic BP (DBP) decreased significantly compared with resting and preinduction (after premedication) values in all groups, whereas significant decreases in T-wave amplitude were seen only in the epinephrine 0.5 µg/kg and saline groups (Table 1). In all groups, IV atropine produced significant increases in SBP and HR compared with values before atropine administration. T-wave amplitudes after IV atropine were significantly smaller than those after premedication but were similar to those before atropine administration (Table 1). There were no significant differences among groups in terms of SBP, DBP, HR, and T-wave amplitudes at rest, 10 min after premedication, and before and 5 min after atropine administration (Table 1). Oxygen saturation was 98% in all patients during the entire course of the study.

View larger version (33K): [in this window] [in a new window]   Figure 1. Changes in heart rate after the IV injection of the test dose containing 0.5, 0.25, and 0.125 µg/kg epinephrine (in 0.1, 0.05, and 0.025 mL/kg 1% lidocaine, respectively) (n = 20 each) with prior 0.01 mg/kg atropine administration in sevoflurane-anesthetized children. Because heart rate was essentially unchanged after saline injections, these data are not presented. Data are mean ± SD. *P < 0.05 versus preinjection values.

View larger version (29K): [in this window] [in a new window]   Figure 2. Changes in systolic blood pressure after the IV injection of the test dose containing 0.5, 0.25, and 0.125 µg/kg epinephrine (in 0.1, 0.05, and 0.025 mL/kg 1% lidocaine, respectively) (n = 20 each) with prior 0.01 mg/kg atropine administration in sevoflurane-anesthetized children. Because systolic blood pressure was essentially unchanged after saline injections, these data are not presented. Data are mean ± SD. *P < 0.05 versus preinjection values.

View larger version (25K): [in this window] [in a new window]   Figure 3. Percent changes in T-wave amplitude determined from lead II electrocardiography after the IV injection of the test dose containing 0.5, 0.25, and 0.125 µg/kg epinephrine (in 0.1, 0.05, and 0.025 mL/kg 1% lidocaine, respectively) (n = 20 each) with prior 0.01 mg/kg atropine administration in sevoflurane-anesthetized children. Because T-wave amplitude was essentially unchanged after saline injections, these data are not presented. Data are mean ± SD. *P < 0.05 versus preinjection values. Data are mean ± SD. *P < 0.05 versus preinjection values.

View larger version (51K): [in this window] [in a new window]   Figure 4. Alteration of T-wave amplitudes in lead II of a 24-mo-old patient before (A) and after (B) the patient received an IV injection of a test dose containing 0.25 µg/kg epinephrine after 0.01 mg/kg atropine IV. Maximal increases in heart rate and T-wave amplitude were 9 bpm and 62%, occurring 35 and 25 s after the test dose injection, respectively.

	Discussion

Top Abstract Introduction Methods Results Discussion References

Our results also suggest that peak T-wave changes may be used as another reliable marker for detecting intravascular injection, because 100% efficacy was demonstrated with a smaller dose of epinephrine (0.25 µg/kg) if a 25% increase in T-wave amplitude was regarded as a positive response. Although the 25% could be an arbitrary number, such a threshold has been used in previous studies (4,5). However, we did not evaluate the ability of the participating anesthesiologist to detect a 25% increase in T-wave amplitude on the oscilloscope, which must be addressed in a blinded, prospective manner before T-wave alterations can be considered as a viable criterion. In addition, to confirm such findings and, possibly, to find a more appropriate criterion using the peak T-wave change, a larger study involving more patients would be required from which the 95% confidence interval should be sought. Furthermore, whether reliable T-wave increases are similarly induced in other electrocardiography leads (5), by the combination of other local anesthetics and epinephrine (8), or with other volatile anesthetics remains to be determined. We also demonstrated that the maximal T-wave changes occurred approximately 10 s earlier than the maximal HR changes. Therefore, close attention should be paid to the electrocardiography monitor for the first minute after the test dose is administered, bearing in mind that such T-wave changes may last for a brief period. Indeed, 60% and 100% of children in the epinephrine 0.5 and 0.25 µg/kg groups, respectively, ceased to satisfy the T-wave criterion of 25% increase after one minute. To maximize the detectability of an intravascular injection of the test dose, we recommend making a continuous record of the electrocardiograph on a strip chart so that transient T-wave changes can be critically analyzed.

The shortcomings of our study are threefold. First, atropine was given to all patients, whereas atropine is not indicated in healthy children undergoing minor surgeries under general anesthesia. However, pretreatment with atropine 10 µg/kg IV has been reported to augment the HR and SBP responses to, and improve the efficacy of, the epinephrine-containing test dose based on the HR and SBP criteria in children anesthetized with halothane and sevoflurane (2,3). At our institution, IV atropine is therefore, considered mandatory in children receiving regional anesthesia with a combined local anesthetic-epinephrine solution. However, it has been reported that without prior IV atropine, decreases (rather than increases) in T-wave amplitude occur in sevoflurane-anesthetized children (9). Second, we did not address hemodynamic responses after the injections of the epinephrine test dose into the epidural vein. However, previous similar studies used the same study design, i.e., injecting test doses into an arm vein and making inferences based on hemodynamic changes and the usefulness of different monitoring techniques (2–4,7). In addition, the difference in hemodynamic consequences between injecting the epinephrine test dose into an arm vein and into an epidural vein has not been previously determined. Finally, our results should be interpreted under the conditions of our protocol, i.e., before surgery immediately after atropine injections. When circulating catecholamine concentrations are higher during or after surgery, HR responses to an intravascular test dose may be less than those reported as a result of down-regulation of the ß-adrenoceptors (10). However, the effects and impact of residual atropine on hemodynamic changes would be more difficult to predict. Although the elimination half-life of IV atropine is approximately five hours in children, and even longer in those less than age two years (11), no correlation has been found between the plasma concentrations of atropine and the respective increase in HR (12). More importantly, because the HR- and SBP-augmenting effect of atropine on test dose injections is probably due to the suppression of baroreflex function to hypertensive stimuli (2,3), the duration of parasympatholytic effects of IV atropine in relation to the duration of surgery would determine hemodynamic changes to the IV test dose at the end of surgery. However, the duration of parasympatholysis produced by IV atropine 0.01 mg/kg has never been determined in children. Based on these considerations, the reliability of the hemodynamic criteria is more likely to be inferior when the epidural catheter is redosed during or after surgery.

The efficacy of detection based on the peak SBP was marginal in our study. Although originally determined in awake adult volunteers with or without ß-blockers (7), the SBP criterion was associated with conflicting results in anesthetized children (2–4). We could demonstrate 100% sensitivity and specificity only after atropine treatment in sevoflurane-anesthetized children (2), whereas others (3,4) demonstrated clinically unacceptable efficacy in halothane- or sevoflurane-anesthetized, atropine-treated children. Although the previous studies were performed using different anesthetics (halothane versus sevoflurane) or slightly different nitrous oxide concentrations (60% vs 67%), the primary explanation of the discrepancy may be the small number of patients involved in each study, i.e., the lack of statistical power.

We confirmed normal sinus rhythm by the preoperative electrocardiography merely to screen for the study. Because the cost of electrocardiography is almost $50.00 in Japan, it is not routinely recommended as a preoperative test for healthy infants and children undergoing minor surgeries. We also continuously recorded lead II on a strip chart for five minutes after the test dose injection. However, the maximal change in the T-wave amplitude occurred within one minute of test dose administration in all patients, which suggests that the longer record is not necessary. These results imply that a typical cost of a strip chart would be $0.30 to $0.80 per case at a chart speed of 25 mm/s. This would be far less expensive than having an additional anesthesiologist document a significant T-wave change.

In conclusion, the IV injection of an epidural test dose consisting of 1% lidocaine with 1:200,000 epinephrine produced dose-dependent increases in HR and T-wave amplitude in sevoflurane-anesthetized, atropine-treated children. To detect an accidental intravascular injection of the test dose, the HR (positive if 10 bpm increase), SBP (positive if 15 mm Hg increase), and T-wave (lead II, positive if 25% increase) criteria are all useful when a full test dose (epinephrine 0.5 µg/kg) was injected intravascularly, whereas the HR and the T-wave criteria are reliable markers for most patients if a half dose of the test dose (epinephrine 0.25 µg/kg) is injected intravascularly.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Matsumiya N, Dohi S, Takahashi H, et al. Cardiovascular collapse in an infant after caudal anesthesia with a lidocaine-epinephrine solution. Anesth Analg 1986;65:1074–6.[Free Full Text]
2. Tanaka M, Nishikawa T. Simulation of an epidural test dose with intravenous epinephrine in sevoflurane-anesthetized children. Anesth Analg 1998;86:952–7.[Abstract]
3. Desparmet J, Mateo J, Ecoffey C, Mazoit X. Efficacy of epidural test dose in children anesthetized with halothane. Anesthesiology 1990;72:249–51.[ISI][Medline]
4. Tanaka M, Nishikawa T. Evaluating T -wave amplitude as a guide for detecting intravascular injection of a test dose in anesthetized children. Anesth Analg 1999;88:754–8.[Abstract/Free Full Text]
5. Fisher QA, Shaffner DH, Yaster M. Detection of intravascular injection of regional anaesthetics in children. Can J Anaesth 1997;44:592–8.[Abstract/Free Full Text]
6. Lerman J, Sikich N, Kleinman S, Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology 1995;82:38–46.[ISI][Medline]
7. Guinard JP, Mulroy MF, Carpenter RL, Knopes KD. Test doses optimal epinephrine content with and without acute beta-adrenergic blockade. Anesthesiology 1990;73:386–92.[ISI][Medline]
8. Freid EB, Bailey AG, Valley RD. Electrocardiographic and hemodynamic changes associated with unintentional intravascular injection of bupivacaine with epinephrine in infants. Anesthesiology 1993;79:394–8.[ISI][Medline]
9. Goujard E, Desparmet J. T wave, ST segment and heart rate changes after test dosing in children anesthetized with sevoflurane [abstract]. Anesthesiology 1998;89:A1249.
10. Tohmeh JF, Cryer PE. Biphasic adrenergic modulation of beta-adrenergic receptors in man. J Clin Invest 1980;65:836–40.
11. Virtanen R, Kanto J, Iisalo E, et al. Pharmacokinetic studies on atropine with special reference to age. Scand 1982;26:297–300.
12. Kanto J, Klotz U. Pharmacokinetic implications for the clinical use of atropine, scopolamine and glycopyrrolate. Acta Anaesthesiol Scand 1988;32:69–78.[ISI][Medline]

This article has been cited by other articles:

				J. Guay The epidural test dose: a review. Anesth. Analg., March 1, 2006; 102(3): 921 - 929. [Abstract] [Full Text] [PDF]

				K. Ogasawara, M. Tanaka, and T. Nishikawa Choice of Electrocardiography Lead Does Not Affect the Usefulness of the T-Wave Criterion for Detecting Intravascular Injection of an Epinephrine Test Dose in Anesthetized Children Anesth. Analg., August 1, 2003; 97(2): 372 - 376. [Abstract] [Full Text] [PDF]

				S. Takahashi, M. Tanaka, and H. Toyooka The Efficacy of Hemodynamic and T-Wave Criteria for Detecting Intravascular Injection of Epinephrine Test Dose in Propofol-Anesthetized Adults Anesth. Analg., March 1, 2002; 94(3): 717 - 722. [Abstract] [Full Text] [PDF]

				J. D. Tobias Caudal Epidural Block: A Review of Test Dosing and Recognition of Systemic Injection in Children Anesth. Analg., November 1, 2001; 93(5): 1156 - 1161. [Full Text] [PDF]

				M. Tanaka, R. Nitta, and T. Nishikawa Increased T-Wave Amplitude After Accidental Intravascular Injection of Lidocaine Plus Bupivacaine Without Epinephrine in Sevoflurane-Anesthetized Child Anesth. Analg., April 1, 2001; 92(4): 915 - 917. [Full Text] [PDF]

				A. K. Ross, J. B. Eck, and J. D. Tobias Pediatric Regional Anesthesia: Beyond the Caudal Anesth. Analg., July 1, 2000; 91(1): 16 - 26. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Tanaka, M. Articles by Nishikawa, T. Search for Related Content PubMed PubMed Citation Articles by Tanaka, M. Articles by Nishikawa, T.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999