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Anesth Analg 2000;90:579-583
© 2000 International Anesthesia Research Society

PEDIATRIC ANESTHESIA

Cardiovascular Criteria for Epidural Test Dosing in Sevoflurane- and Halothane-Anesthetized Children

Sibylle A. Kozek-Langenecker, MD*, Peter Marhofer, MD{dagger}, Karin Jonas, MD{dagger}, Tom Macik, MD{dagger}, Georg Urak, MD{dagger}, and Margot Semsroth, MD{dagger}

Departments of *Anesthesiology and Intensive Care B, and {dagger}Anesthesiology and General Intensive Care A, University of Vienna, School of Medicine, Vienna, Austria

Address for correspondence and reprints to Sibylle A. Kozek-Langenecker, MD, Department of Anesthesiology and General Intensive Care, University of Vienna, 18–20 Währinger Gürtel, 1090-Vienna, Austria.


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
This study was designed to determine the detectability of a simulated IV test dose in children during administration of general anesthesia by using heart rate (HR), systolic blood pressure (SBP), and T wave criterion. Forty-two children (0.5–8 yr old) received an IV injection containing epinephrine 0.5 µg/kg and another IV injection containing saline during either halothane or sevoflurane anesthesia administration at 1.0 minimum alveolar concentration in nitrous oxide. A positive test response was defined as a change in T wave amplitude >=25%, SBP increase >=15 mm Hg, and HR increase >=10 bpm. By using the T wave, SBP, and HR criteria, a positive response rate to epinephrine was 100%, 95%, and 71%, respectively, during sevoflurane, and 90%, 71%, and 71%, respectively, during halothane anesthesia administration. These data suggest that the T wave criterion is superior to conventional hemodynamic criteria, and that sevoflurane attenuates T wave and SBP responses less than halothane; however, chronotropic responses are similar to halothane.

Implications: We found a greater reliability of the T wave criterion over conventional hemodynamic criteria for detecting intravascular injection of a simulated epidural test dose. Sevoflurane may increase the likelihood of recognition of an accidental intravascular injection of epinephrine-containing solutions in clinical practice compared with halothane.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Inadvertent intravascular injection of local anesthetics can result in serious cardiovascular and central nervous system toxicity (1,2). The incidence of intravascular entry varies between 0.4% and 5.6% of epidural attempts in infants and children (2,3). In clinical practice, detection of an accidental intravascular needle position has been reported to remain undetected by aspiration of blood before injection of local anesthetics in 86% and by epidural test dosing in 17% of pediatric patients when based on heart rate (HR) criteria (3). Even with direct IV injection of an epinephrine-containing solution into a peripheral arm vein, HR did not increase by >10 bpm in 29% of children during halothane anesthesia administration (4). In contrast, during the administration of sevoflurane anesthesia, Tanaka and Nishikawa (5) reported a positive HR response to IV epinephrine in 15 of 15 children. Whereas systolic blood pressure (SBP) increased by >15 mm Hg in 100% of children during halothane anesthesia administration (4), only 67% of sevoflurane-anesthetized children met the SBP criterion for epidural test dosing (5). In a previous study, we found a difference between halothane and sevoflurane on the responsiveness to isoproterenol (6). No comparative study between halothane and sevoflurane on the hemodynamic responsiveness to epinephrine is available.

Previous reports suggested that changes in T wave morphology induced by epinephrine could serve as a marker of intravascular injection during epidural test dosing in children (3,7). Recently, the efficacy of the T wave criterion (defined as a change in T wave amplitude >=25%) for detecting IV injection of a simulated test dose consisting of lidocaine and epinephrine has been documented in sevoflurane-anesthetized children (8). It remains uncertain whether similar changes in T wave amplitude could be elicited by an IV test dose during halothane anesthesia administration. Accordingly, we determined the efficacy of the HR, SBP, and the T wave criterion for diagnosis of IV epinephrine in children under stable halothane and sevoflurane anesthesia in a prospective, randomized, double-blinded study.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Institutional review board approval was obtained before this study, and informed parental consent was obtained for each patient. Forty-two ASA physical status I children ages 0.5 to 8 yr with normal sinus rhythm undergoing elective minor surgery were involved. Children fasted for 4 to 6 h and received premedication with 1 mg/kg rectal midazolam (<=15.0 mg) 30 min before the induction of anesthesia. By using computer-generated tables, patients were randomly assigned to be anesthetized with either halothane (n = 21) or sevoflurane (n = 21). Anesthesia was induced with a face mask by using 70% nitrous oxide in oxygen and incremental dosing of anesthetics every three to five breaths. Halothane was begun at 0.5% and increased by increments of 0.5% to 1%, whereas sevoflurane was begun at 1% and increased by increments of 1.5% until the patient was unconscious. The fresh gas flow exceeded 4 L/min. A standard anesthesia machine (Cicero; Draegerwerk AG, Luebeck, Germany) with a sevoflurane and halothane vaporizer (Draeger-Vapor 19.1; Draegerwerk AG) exclusively calibrated for each anesthetic was used for delivery. Inhaled anesthesia via a face mask was continued by using assisted or controlled ventilation, and an IV catheter was inserted for infusion of 5 mL/kg lactated Ringer’s solution, followed by a continuous infusion administered at a rate of 5 mL · kg-1 · h-1 throughout the study period. Neuromuscular blocking drugs and atropine pretreatment were not administered because the latter it is no longer routinely used in pediatric patients undergoing general anesthesia (9). After inserting a laryngeal mask, ventilation was controlled to maintain an ETCO2 tension between 30 and 35 mm Hg, and an end-tidal anesthetic concentration of 1.0 minimum alveolar anesthetic concentration (MAC) of inhaled anesthetic adjusted for age in 70% nitrous oxide and 30% oxygen (10,11). End-tidal gas concentrations were sampled at the proximal end of the laryngeal mask at a rate of 50 mL/min and were recorded continuously. Rectal temperature was maintained between 36°C and 37°C. Electrocardiogram (ECG) lead II (Megacart; Siemens-Elema AB, Solma, Sweden) and pulse oximetry were monitored continuously throughout the study period. Electrocardiograph records were subsequently analyzed for changes in T wave amplitude measured from the isoelectric P-QRS line to the peak of the T wave. Automated noninvasive oscillometric blood pressure (HP Model 68S; Hewlett Packard, Boebingen, Germany) was recorded in 30-s intervals throughout the study. When hemodynamic variables and end-tidal gas concentrations were stable for 10 min, each patient received two test doses injected via a peripheral arm vein to simulate the intravascular administration of an epidural test dose. The volume of the test injections was standardized at 0.2 mL/kg. One test injection consisted of epinephrine 0.5 µg/kg. The dose of epinephrine used represents the recommended contents in an epidural test dose (12,13). The other test injection consisted of saline. The sequence of test doses was assigned randomly. The second test dose was administered either 5 min after the previous injection when there was no change in HR, or 5 min after the HR had returned to baseline in response to the previous injection. The data-collecting investigator and the investigator analyzing the ECG records were blinded to the anesthetic group and the sequence of test injection. Measurements were performed before surgical incision.

As in the study by Fisher et al. (3), we defined an increase or decrease in T wave amplitude >=25% as a positive T wave criterion. In addition, a positive response to intravascular injection of a test dose was defined as a HR increase of >=10 bpm (HR criterion) (4,5) and an increase in SBP of >=15 mm Hg (SBP criterion) occurring within 2 min of injection (13). Sensitivity (true-positives/[true-positives + false-negatives]), specificity (true-negatives/[true-negatives + false-positives]), and positive (true-positives/[true-positives + false-positives]) and negative predic- tive values (true-negatives/[true-negatives + false-negatives]) were calculated for each test criterion and all anesthesia groups. A power analysis based on a pilot study revealed that a minimal study size of 36 people would provide 80% power (0.05 {alpha}, two-tailed, 0.20 ß, two-tailed) of detecting a change in T wave amplitude of 0.05 mV or greater in response to IV epinephrine 0.5 µg/kg in sevoflurane-anesthetized children. Differences in frequency distribution between the cardiovascular criteria and the two anesthetic groups were analyzed by using Cochran’s Q and by {chi}2 test. Correlations between baseline T wave amplitudes immediately before test dose injection and maximal changes in T wave amplitude were analyzed by using Pearson’s correlation coefficient. Demographic data and hemodynamic data before test dose injections were expressed as mean ± SD and compared with the two anesthesia groups by using an unpaired Student’s t-test. Changes in T wave amplitude over time within each group were analyzed by using analysis of variance for repeated measures followed by paired Student’s t-test. A P < 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
There were no significant differences between the sevoflurane and halothane groups in terms of age (2.6 ± 1.7 vs 2.7 ± 1.9 yr), weight (14 ± 5 vs 14 ± 4 kg), and height (89 ± 15 vs 89 ± 13 cm). Baseline HR immediately before test dose injections was significantly higher in the sevoflurane group (119 ± 18 bpm) compared with the halothane group (106 ± 18 bpm). Baseline SBP immediately before test dose injections was similar in both groups (96 ± 10 vs 93 ± 11 mm Hg). T wave amplitude immediately before test dose injections was significantly lower in the sevoflurane group (0.19 ± 0.07 mV) compared with the halothane group (0.31 ± 0.08 mV).

IV injection of epinephrine caused changes in T wave amplitude, SBP, and HR, whereas cardiovascular variables remained stable during saline injection under stable sevoflurane and halothane anesthesia. Changes in T wave amplitude after IV epinephrine are shown in Figure 1. During sevoflurane anesthesia, mean maximal increase in T wave amplitude occurred 20 ± 8 s after injection and values returned to baseline until 1 min after test injections. During halothane anesthesia, mean maximal decrease in T wave amplitude occurred 51 ± 7 s after the injection and T wave amplitude remained decreased until 4 min after the injection.



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  		Figure 1. Changes in T wave amplitude determined from electrocardiography lead II after IV injection of the test dose containing epinephrine 0.5 µg/kg during sevoflurane and halothane anesthesia administration at 1 minimum alveolar concentration in 70% nitrous oxide (n = 21 each group). Because T wave amplitude remained unchanged after saline injections, these data are not presented. Data are mean ± SD *P < 0.05 versus preinjection values.

 
Sensitivity, specificity, and positive and negative predictive values in response to IV epinephrine are summarized in Table 1. A 25% change (increase or decrease) in T wave amplitude has been used as a threshold of a positive response. All children in the sevoflurane group met the T wave criterion resulting in all sensitivity, specificity, and positive and negative predictive values being 100%. Of patients receiving sevoflurane anesthesia 71% showed reliable increases in T wave amplitude, whereas 71% of patients receiving halothane anesthesia showed reliable decreases rather than increases in T wave amplitude. In both anesthesia groups, the T wave criterion was more sensitive than the HR and SBP criteria. The difference in frequencies of positive HR versus T wave responses reached statistical significance in the sevoflurane group (P < 0.05). T wave and SBP criteria were more sensitive during sevoflurane anesthesia compared with halothane anesthesia. The difference in sensitivities of the SBP criterion between the two anesthetic groups was statistically significant (P < 0.05). No significant correlation between baseline T wave amplitudes immediately before test dose injection and maximal changes in T wave amplitude could be found.


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  		Table 1. Sensitivity, Specificity, Positive and Negative Predictive Values of a Simulated Epidural Test Dose Containing Epinephrine 0.5 µg/kg in Children During Sevoflurane or Halothane Anesthesia Administration
 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
In pediatric patients, regional anesthetic techniques are most often performed during the administration of general anesthesia (14). Because inhaled anesthetics differ in their depressant actions and hemodynamic responses to catecholamines (6), it is important to determine the efficacy of epinephrine-containing test doses under the influence of different anesthetics. In general, there are three test criteria for diagnosis of accidental intravascular injection of the test dose applicable: 1) the HR criterion; 2) the SBP criterion; and 3) the T wave criterion. Our study demonstrates that a simulated IV test dose containing epinephrine is unreliable during both sevoflurane and halothane anesthesia administration at 1 MAC in 70% nitrous oxide when based on the HR criterion. Sensitivity of the HR criterion was 71% during both sevoflurane and halothane anesthesia. Our results are similar to those of Desparmet et al. (4) who found a sensitivity of 71% in children anesthetized with 1% halothane and nitrous oxide after IV injection of a simulated test dose. However, our results are in contrast to a previous report by Tanaka and Nishikawa (5) who observed a HR increase >=10 bpm in 100% of children anesthetized with sevoflurane at 1 MAC in nitrous oxide. The reason for the discrepancy between the latter study and our findings is unclear and may be related to the greater statistical power of our current study. Our results further demonstrate that the SBP criterion is more sensitive for detection of IV epinephrine during sevoflurane anesthesia (95%) compared with halothane anesthesia (71%). However, in agreement with previous investigators (4,5), we conclude that short-lived SBP increases may easily be missed in clinical practice unless noninvasive measurements of blood pressure are performed at the shortest intervals possible.

Our study demonstrates that changes in T wave amplitude provide evidence of intravascular injection of epinephrine in children under both halothane and sevoflurane anesthesia. All children receiving sevoflurane anesthesia met the T wave criterion in response to direct IV injection of epinephrine without false-positive responses after saline injection, resulting in all sensitivity, specificity, and positive and negative predictive values being 100%. The T wave criterion identified IV epinephrine in 90% of children receiving halothane anesthesia. We observed higher baseline T wave amplitudes immediately before test dose injections in children during stable halothane anesthesia compared with sevoflurane anesthesia administration. However, we found no significant relationship between baseline T wave amplitude and peak change in T wave amplitude in any of the groups, suggesting that different baseline T wave amplitude does not influence the efficacy of the T wave criterion.

Both an increase as well as a decrease in T wave amplitude >=25% has been proposed as a diagnostic criterion for intravascular injection in clinical practice (3). The IV injection of epinephrine induced an increase in T wave amplitude in the majority of patients receiving sevoflurane, whereas flattening or inversion of the T wave predominated in patients receiving halothane. Peak increases in T wave amplitude occurred almost within a circulation time, approximately 30 seconds earlier than those of maximal decreases in T wave amplitude and other hemodynamic alterations. It is not clear from our study why halothane and sevoflurane at 1 MAC differ in their effects on cardiac repolarization in the presence of epinephrine. Modifications of cardiac electrophysiologic properties (15–18), basal sympathetic, and parasympathetic tone (19,20) may, in part, be responsible. Recently, an age-specific effect of IV epinephrine on T wave morphology has been reported (8,21). This phenomenon, however, cannot explain the difference in magnitude and time course of T wave changes we observed because groups were comparable with respect to patient age. Both positive and negative changes in T wave amplitude exceeding the threshold of 25% could be easily detected visually on the strip chart, as in previous studies (3,8). Epinephrine-induced T wave changes have a characteristic crescendo/decrescendo pattern, are sustained for more than four beats, and precede HR and SBP changes (3). Atropine pretreatment before test dosing has been found to reduce the incidence of flattening in favor of T wave increases during sevoflurane anesthesia (22). The effect of atropine on the T wave configuration under halothane remains to be determined.

One limitation of our study design is the use of a single dose of 0.5 µg/kg epinephrine recommended for epidural test dosing (13). Our observations cannot predict the reliability of the T wave criterion for detecting intravascular injection of an epidural test dose in clinical practice where only a fraction of the test dose may enter the vascular space. Although our study indicates the potential usefulness of the T wave as a marker for epidural test dosing in anesthetized children, this technique cannot be recommended until further studies have determined the dose-response relationship for epinephrine-induced changes in T wave amplitude, HR, and SBP.

The present results suggest that sevoflurane may be safer than halothane in combined general and regional anesthetic techniques in pediatric patients. Sevoflurane may increase the likelihood of recognition of accidental intravascular injection of epinephrine-containing solutions, thus preserving the efficacy of an epidural test dose. Sevoflurane appears to attenuate blood pressure and ECG responses to the mixed {alpha}- and ß-adrenergic agonist epinephrine (23) less than halothane and the chronotropic responses similar to halothane. Comparative studies between halothane and sevoflurane are not available; however, our findings indicate that sevoflurane preserves the potential for vasoconstriction and the positive inotropic response better than halothane, as suggested previously (24,25). The increased blood pressure stimulus during sevoflurane anesthesia may have induced greater reflex decreases in the cardiac R-R interval resulting in chronotropic responses similar to halothane. Further studies are warranted to substantiate the difference between sevoflurane and halothane on the efficacy of the epidural test dose containing epinephrine at varying MAC values in infants and children.


   Acknowledgments
 
Supported in part by a grant from the Baxter Allegiance Fellowship of the Ludwig Boltzmann Institute for Anesthesia and Intensive Care to TM.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication November 2, 1999.




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Lippincott, Williams & Wilkins 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 HighWire Press