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PEDIATRIC ANESTHESIA

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

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

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

	Abstract

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Accidental intravascular injection of an epinephrine-containing test dose increases T-wave amplitude of lead II electrocardiogram (EKG) in anesthetized children. We designed this study to test whether the choice of EKG lead would affect the usefulness of simulated intravascular test dose. We studied 32 ASA physical status I infants and children (aged 6–49 mo) undergoing elective surgeries during 1.0 minimum alveolar anesthetic concentration sevoflurane and 67% nitrous oxide in oxygen. When hemodynamic stability was obtained, all subjects received IV saline 0.1 mL/kg, followed 4 min later by an IV test dose (0.1 mL/kg) consisting of 1% lidocaine with 1:200,000 epinephrine (epinephrine 0.5 µg/kg) via a peripheral vein to simulate the intravascular injection of the test dose. Heart rate and systolic blood pressure were recorded every 20 and 60 s, respectively, and leads II (n = 32), V₅ (n = 32) and either lead I (n = 15) or III (n = 17), choosing the one with greater preinjection T-wave amplitude, were continuously recorded for 4 min after the saline and the test dose injections. An IV test dose produced significant increases in heart rate, systolic blood pressure, and T-wave amplitude of all EKG leads studied in all subjects, whereas IV saline elicited no changes in these variables. Maximal increases in T-wave amplitude of leads II, I, III, and V₅ were 158% ± 69%, 175% ± 78%, 147% ± 89%, and 170% ± 72%, respectively (mean ± SD, P > 0.05). There was no significant difference in temporal changes in T-wave amplitude among the 4 leads, and sensitivity and specificity were 100% on the basis of the T-wave criterion irrespective of the lead examined. Our results indicate that leads II, I, III, and V₅ of EKG are equally effective for detecting intravascular injection of the epinephrine-containing test dose in sevoflurane-anesthetized children.

IMPLICATIONS: To determine whether an epidurally administered local anesthetic has been accidentally injected into a blood vessel, a small dose of epinephrine is often added to a local anesthetic. We found that increases in T-wave amplitude in leads I, II, III, and V₅ of the electrocardiogram are equally sensitive and specific for detecting intravascular injection of the epinephrine-containing test dose in sevoflurane-anesthetized infants and children.

	Introduction

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Epidural anesthesia is often combined with general anesthesia and used for postoperative analgesia. Epidural anesthesia is often performed under general anesthesia in children. To avoid life-threatening central nervous system and cardiac complications associated with a large amount of local anesthetic solution accidentally injected into the epidural venous plexus (1), a small dose of epinephrine is added to local anesthetics (2). A peak heart rate (HR) increase 10 bpm and a systolic blood pressure (SBP) increase 15 mm Hg have been considered reliable indicators for intravascular injection in anesthetized children (3–5). More recently, an increase in T-wave amplitude of lead II electrocardiogram (EKG) 25% has been shown to be a reliable testing threshold as the HR criterion when a full test dose containing 0.5 µg/kg epinephrine is injected IV (5), and more sensitive than the HR and SBP criteria after an IV injection of a fractional test dose (6). In previous studies, however, only lead II of the EKG has been examined only after atropine pretreatment (5–7), and whether changes in T-wave morphology of similar magnitude would occur in other leads after IV test dose without atropine remains to be determined.

We hypothesized that IV injection of an epinephrine-containing test dose would produce increases in T-wave amplitude of similar magnitude, and thus would produce 100% sensitivities and specificities based on the T-wave criterion in EKG leads other than lead II. Accordingly, we studied changes in EKG morphology in leads I, II, III, and V₅ after simulated IV test dose in pediatric patients during general anesthesia.

	Methods

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After IRB approval and informed, parental consent, 32 ASA physical status I infants and children, aged 6–49 mo, with a normal sinus rhythm determined by preoperative EKG, 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 clear liquid 4 h before the anticipated time of general anesthesia induction. They also received midazolam 0.5 mg/kg orally 30 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 semi-closed 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, standard limb leads and precordial V₅ of EKG (Viridia; Hewlett-Packard, Palo Alto, CA), 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, and then controlled. After the trachea was intubated without muscle relaxant under sevoflurane in oxygen, anesthesia was maintained with 1 minimum alveolar anesthetic concentration sevoflurane adjusted for age (8) and 67% nitrous oxide in oxygen. End-tidal CO₂ tension was maintained between 30 and 35 mm Hg by controlled ventilation (Capnomac Ultima; Datex, Helsinki, Finland). When hemodynamic variables and end-tidal concentrations were stable for at least 10 min after anesthetic induction, normal saline 0.1 mL/kg was first administered IV, followed 4 min later by an IV test dose (0.1 mL/kg) consisting of 1% lidocaine with 1:200,000 epinephrine (epinephrine 0.5 µg/kg) via a peripheral vein to simulate the intravascular injection of the test dose. The study solution was prepared and coded by an anesthesiologist not involved in the study, and injected over 5 s by a blinded observer (MT) before initiation of the surgery with the patient in the supine position. HR and SBP were recorded every 20 and 60 s, respectively, and leads II, V₅, and either lead I or III, choosing the one with greater preinjection T-wave amplitude, were continuously recorded in a strip-chart. In addition, maximal HR, SBP, and T-wave responses were noted during the 4-min observation period after the study drug injection. Typically, we began hemodynamic measurements 20–25 min after anesthesia induction.

Anesthetic management and hemodynamic measurements of all patients were made by one of the authors (KO). T-wave measurements were made subsequently at later, separate, occasions using EKG strips and at random order by one of the authors (KO), who was informed of a 25% increase in T-wave amplitude as a positive threshold, but remained blinded to the EKG lead studied, study drugs, hemodynamic alterations, name of the subject, and date of surgery. The high- and low-frequency filters of EKG were 0.5 and 40 Hz, respectively (monitor mode). The calibration of the recorder was set at 0.5 mV/cm, whereas the chart speed was set at 25 mm/s.

A power analysis based on a previous report revealed that >12 patients would provide a power >0.8 (P = 0.05) for detecting a 25% change in T-wave amplitude (6). Positive HR, SBP, and T-wave changes to the IV test dose were prospectively defined from previous reports: positive if a HR increase was 10 bpm (modified HR criterion), an SBP increase was 15 mm Hg, and an increase in T-wave amplitude was 25%, occurring within 2 min of study drug administrations (3,4,9). We calculated 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 were presented as mean ± SD unless otherwise indicated. Statistical analysis was performed by two-way analysis of variance for repeated measurements with respect to time and drugs (saline versus test dose), and when a significant difference was detected over time, was followed by paired t-test with Bonferroni’s correction. A P value < 0.05 was considered to be statistically significant.

	Results

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The average age, weight, and height of the subjects were 18 ± 13 mo, 9.7 ± 3.1 kg, and 75 ± 13 cm, respectively. Although preinjection SBP and diastolic BP (89 ± 11 and 43 ± 8 mm Hg, respectively) were significantly less than preinduction values (105 ± 12 and 54 ± 8 mm Hg, respectively), preinjection values of the T-wave amplitudes of leads II, I, III, and V₅ (0.38 ± 0.18, 0.24 ± 0.11, 0.26 ± 0.13, and 0.30 ± 0.19 mV, respectively) and HR (127 ± 11 bpm) did not change significantly compared with the corresponding preinduction values (data not shown).

IV injection of the epinephrine-containing test dose produced biphasic HR response, a significant increase from 20 to 60 s followed by a decrease from 100 to 240 s, whereas SBP showed a monophasic increase from 60 to 180 s after test dose injections (Fig. 1). Mean maximal increases in HR and SBP were 20 ± 6 bpm and 36 ± 7 mm Hg, occurring at 28 ± 7 and 67 ± 20 s after the test dose injections, respectively. Significant increases in T-wave amplitudes were seen in leads II, III, and V₅ until 120 s after the test dose injections (Fig. 2). Maximal absolute values of T-wave amplitudes of leads II, I, III, and V₅ were 0.60 ± 0.25, 0.42 ± 0.17, 0.39 ± 0.23, and 0.50 ± 0.22 mV, respectively. No significant difference was detected in percent changes in T-wave amplitude at any intervals among the four leads studied (Fig. 2).

View larger version (30K): [in this window] [in a new window]   Figure 1. Changes in heart rate and systolic blood pressure after IV injection of an epidural test dose consisting of 1% lidocaine with 1:200,000 epinephrine (epinephrine 0.5 µg/kg) in sevoflurane-anesthetized infants and children (n = 32). Because heart rate and systolic blood pressure were unchanged after saline injections, these data are not presented. Data are mean ± SD *P < 0.05 compared with preinjection values.

View larger version (24K): [in this window] [in a new window]   Figure 2. Percent changes in T-wave amplitude determined from leads II (n = 32), I (n = 15), III (n = 17), and V5 (n = 32) of the electrocardiogram after IV injection of an epidural test dose consisting of 1% lidocaine with 1:200,000 epinephrine (epinephrine 0.5 µg/kg) in sevoflurane-anesthetized infants and children. Because T-wave amplitude remained unchanged after saline injections, these data are not presented. Data are mean ± SD. No significant difference was detected among the four leads studied by repeated-measures analysis of variance. *P < 0.05 compared with preinjection values. Max = the time when the maximal T wave occurred in each patient after the simulated IV injection of the test dose.

No ventricular or supraventricular arrhythmia was observed in any patient throughout the study period.

	Discussion

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The present study demonstrated that increases in T-wave amplitude of leads II, I, III, and V₅ were of similar magnitude in response to the simulated IV test dose containing a full dose of epinephrine (0.5 µg/kg). In addition, the sensitivity and specificity of T-wave criterion were 100%, and did not depend on the EKG leads studied in sevoflurane-anesthetized infants and children. These results suggest that the choice of the EKG lead may not be important for detecting inadvertent IV injection of the test dose under the conditions of our study. Clinical usefulness of the T-wave morphology as a diagnostic marker is highlighted when a smaller test dose is injected intravascularly (6). Sensitivity and negative predictive value based on the T-wave criterion were both 100% after the simulated IV test dose containing 0.25 µg/kg epinephrine (half the standard dose) in sevoflurane-anesthetized, atropine-treated children, as might occur when the tip of a multi-orifice epidural catheter migrates into the blood vessel (6). However, sensitivities on the basis of the HR and SBP criteria were 85% and 60%, respectively, during sevoflurane anesthesia (6). Whether changes in T-wave amplitude of similar magnitude would occur in leads other than lead II after a fractional IV test dose remains to be determined.

Even though the exact mechanism of the increased T-wave amplitude caused by the IV test dose remains undetermined in our study, changes in T-wave amplitude of similar extent in all EKG leads suggest that this phenomenon is not a localized, but a generalized effect of epinephrine, lidocaine, or both on the myocardium. An increase in T-wave amplitude is a consistent finding after a simulated IV test dose containing epinephrine plus lidocaine or bupivacaine (5–7,10) in children less than six years of age, whereas IV injections of epinephrine- or isoproterenol-containing test doses without a local anesthetic elicit variable responses (9,10). In addition, Kozek-Langenecker et al. (7) found that T-wave amplitude decreases in most halothane-anesthetized children after IV injections of epinephrine (0.5 µg/kg) alone. These results suggest that the increase in T-wave amplitude after the IV injection of lidocaine plus epinephrine is not simply a manifestation of ß-adrenoceptor-mediated response (10). A case report showed that accidental intravascular injection of lidocaine plus bupivacaine without epinephrine solution elicited a marked increase in T-wave amplitude in a two-month-old infant during sevoflurane anesthesia (11). This case report, per se, indicates that the T-wave augmentation may occur as a result of systemic effect of local anesthetic. However, to determine the exact mechanism for the characteristic EKG changes after the IV test dose in anesthetized children, further study is warranted with a protocol that focuses on the effect of a single drug, epinephrine or a local anesthetic, on the EKG morphology, rather than studying their combined effects.

Similar to previous studies, the present study findings also demonstrated unsatisfactory usefulness of the SBP criterion for detecting intravascular injection of the epinephrine test dose compared with the HR and T-wave criteria (4–6,10). The SBP criterion has originally been derived from cardiovascular responses to a simulated IV test dose containing 10–15 µg of epinephrine in awake adult volunteers (12), and its superior effectiveness has been verified under the circumstance of depressed HR responses to epinephrine, such as in the elderly (13), anesthetized adults using isoflurane or sevoflurane (14,15), as well as sedated patients using fentanyl and midazolam (16). Limited clinical usefulness of the SBP criterion in the pediatric population does not seem dependent on the measurement intervals of the noninvasive BP, but may be attributed to the inherent difference in hemodynamic responses to IV epinephrine between the adult and pediatric population.

In contrast to our study’s findings, Shiga et al. (17) showed that mean maximal increase in T-wave amplitude was 71% after the simulated IV test dose consisting of 1% lidocaine 0.1 mL/kg plus epinephrine 0.5 µg/kg, and 90% sensitivity based on the T-wave criterion (positive if 25% increase in amplitude) in sevoflurane-anesthetized children. Besides lack of power, i.e., small number of subjects involved in our study, the discrepancy between Shiga et al.’s study and our present results may be explained by their older population (mean age = 53 ± 25 months, range 18–90 months), because there is a tendency that older children exhibit less increase in T-wave amplitude (5). Thus, the application of this criterion requires caution in children more than six years of age. In anesthetized adult patients, decreases in T-wave amplitude have been reported after a simulated IV test dose containing epinephrine (15), suggesting an age-specific effect of IV epinephrine test dose on T-wave morphology. It would, therefore, be of value to determine the cutoff age above which the criterion using the T-wave amplitude cannot be applied. Another drawback of the T-wave criterion would be that preexisting T-wave abnormality associated with bundle branch block or ventricular hypertrophy in some congenital cardiac anomalies may limit its application (18). Finally, one may argue that choosing either leads I or III depending on the greater T-wave amplitude may introduce bias, rather than studying all four leads at a time. However, the number of EKG leads studied had to be limited to three, because our equipment could only accommodate records of three EKG leads data. We chose lead II because it is the most frequently monitored in clinical practice, whereas V₅ was selected as a representative of precordial leads. The last lead, either I or III, was selected based on the preinjection T-wave amplitude, because greater absolute amplitude would be associated with less error associated with the T-wave measurement.

In conclusion, our results indicate that leads II, I, III, and V₅ of the EKG were equally reliable for detecting an intravascular test dose containing 0.5 µg/kg epinephrine in 1% lidocaine based on the T-wave criterion (positive if 25% increase in amplitude) in children anesthetized with sevoflurane.

	References

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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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Ogasawara, K. Articles by Nishikawa, T. Search for Related Content PubMed PubMed Citation Articles by Ogasawara, K. Articles by Nishikawa, T. Related Collections Cardiovascular Pediatrics Regional Anesthesia Pharmacology