Epidural anesthesia and analgesia are increasingly used in combination with general anesthesia. The inability to aspirate blood from an epidural catheter does not ensure extravascular placement (1), and thus some authors have advocated the routine use of an epinephrine-containing test dose. Although the efficacy of repeated injections of the test dose has not been substantiated (2), objective hemodynamic alterations, such as heart rate (HR) and systolic blood pressure (SBP), have been reported to indicate intravascular injection of the test dose during general anesthesia (3,4). More recently, a decrease in T-wave amplitude by ≥25% has been introduced as a T-wave criterion (5). In contrast to hemodynamic changes elicited by the simulated IV test dose, the extent of T-wave reductions seems not to be affected by the depth of general anesthesia, the choice of anesthetics used, or the state of consciousness (5–7). Furthermore, the efficacy of the T-wave criterion was reported to be superior to that of the HR (positive if ≥10 bpm increase) or SBP (positive if ≥15 mm Hg increase) criteria and their combination when a fractional dose of the test dose was injected intravascularly (8). Even though these results suggest clinical usefulness and reliability of the T-wave criterion for detecting intravascular injection, only Lead II of the electrocardiogram (EKG) has been studied previously, and whether changes in T-wave morphology of similar magnitude would occur in other leads after an IV test dose remains to be determined.
Accordingly, we designed this prospective, single-blinded study to test the hypothesis that the simulated IV test dose containing epinephrine would produce decreases in T-wave amplitude of similar magnitude in EKG leads other than Lead II and, thus, that sensitivities and specificities of 100% would result on the basis of the T-wave criterion in adult patients during general anesthesia.
The study protocol was approved by the Human Research Committee of the University of Akita School of Medicine, and informed consent was obtained from each patient. Thirty-five nonpregnant, ASA physical status I patients, who were free of cardiovascular, pulmonary, and neurological disorders and were scheduled to undergo elective surgeries, were enrolled.
All patients arrived at the operating room after an 8- to 10-h fast without premedication. Standard limb leads and precordial V5 of the EKG (Viridia; Hewlett-Packard, Palo Alto, CA) and oxyhemoglobin saturation were monitored continuously throughout the study. A radial arterial catheter was placed after local anesthesia infiltration, with which subsequent blood pressure measurements were made. Lactated Ringer’s solution was maintained at a constant rate of approximately 15 mL · kg−1 · h−1 through a peripheral 18-gauge IV catheter until the end of the study. After the induction of general anesthesia with thiopental 5 mg/kg IV, endotracheal intubation was facilitated with vecuronium 0.1 mg/kg IV. Anesthesia was then maintained with end-tidal sevoflurane 2% and 67% nitrous oxide in oxygen (Capnomac Ultima; Datex, Helsinki, Finland), whereas ventilation was controlled to maintain end-tidal carbon dioxide tension at 30–35 mm Hg. When three measurements of SBP and HR, determined at 1-min intervals, were within ±5% of the previous value, steady end-tidal sevoflurane concentration was obtained for 5 min (end-tidal sevoflurane constantly showing 2% at constant inspiratory concentration), and at least 20 min had elapsed after the induction of general anesthesia, normal saline 3 mL was first administered IV, followed 4 min later by 1.5% lidocaine 3 mL containing 15 μg of epinephrine (1:200,000) IV as a simulated intravascular test dose via a peripheral venous line over 5 s. HR, SBP, Leads II and V5, and either Lead I or III (whichever had a greater T-wave amplitude) were continuously recorded. In addition, maximum HR, SBP, and T-wave responses were noted during the 4-min observation period. Typically, we began hemodynamic measurements 25–30 min after anesthesia induction. All hemodynamic and EKG recordings were made in the supine position before initiation of the patient’s scheduled surgery.
Anesthetic management, including study drug injections and hemodynamic measurements of all patients, was performed by one of the authors (MT), who was not blinded to the study drug. HR and SBP were analyzed at 20-s intervals for 4 min. The analysis of T-wave morphology was made by using a strip chart of each EKG lead at its maximum deflection and at 60-s intervals for 4 min. T-wave measurements were performed subsequently at separate occasions and at random order by an observer who was informed of a 25% decrease in T-wave amplitude as a positive threshold but remained blinded to the EKG lead studied, study drugs, and hemodynamic alterations. The high- and low-frequency filters of the 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 more than 15 patients would provide a power of >0.8 (P = 0.05) for detecting a 25% change in T-wave amplitude (5,9). Positive HR, SBP, and T-wave changes to the IV test dose were prospectively defined from previous reports: positive if an HR increase was ≥10 bpm (modified HR criterion) (4), an SBP increase was ≥15 mm Hg (10), and a decrease in T-wave amplitude was ≥25%(5), occurring within 2 min of study drug administration. 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 (true negatives/[true negatives + false negatives]) predictive values. 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, this was followed by a paired Student’s t-test with Bonferroni’s correction. A P value of <0.05 was considered to be statistically significant.
The average age, weight, and height of the subjects were 34 ± 13 yr, 56.2 ± 12.0 kg, and 162 ± 13 cm, respectively. Although preinjection SBP, diastolic blood pressure, and HR (97 ± 9 mm Hg, 56 ± 8 mm Hg, and 70 ± 10 bpm, respectively) were significantly less than preinduction values (126 ± 14 mm Hg, 68 ± 6 mm Hg, and 77 ± 10 bpm, respectively), preinjection values of the T-wave amplitudes of Leads II, I, III, and V5 (0.34 ± 0.16 mV, 0.21 ± 0.10 mV, 0.34 ± 0.14 mV, and 0.36 ± 0.17 mV, respectively) did not change significantly compared with preinduction values of the corresponding lead.
IV injection of the epinephrine-containing test dose produced a biphasic HR response, a significant increase followed by a decrease, whereas SBP showed a monophasic increase (Fig. 1). The mean maximum increases in HR and SBP were 23 ± 9 bpm and 46 ± 22 mm Hg, occurring at 35 ± 11 s and 82 ± 26 s after the test-dose injections, respectively. However, significant decreases in T-wave amplitudes were seen in all leads until 120 s after the test-dose injections (Fig. 2). The mean maximum decreases in T-wave amplitudes of Leads II, I, III, and V5 were −87% ± 13%, −88% ± 8%, −94% ± 15%, and −86% ± 16%, respectively, and there was no significant difference in the extent of T-wave reductions among the leads studied.
Two of 35 patients developed an HR increase of <10 bpm, whereas the HR increase was <10 bpm after saline injections in all patients, resulting in a sensitivity of 94%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 95% on the basis of the modified HR criterion. However, SBP was >15 mm Hg after the test-dose injections but was <15 mm Hg after saline injections in all patients. Thus, sensitivity, specificity, and positive and negative predictive values were 100% on the basis of the SBP criterion. Similarly, on the basis of the T-wave criterion, sensitivity, specificity, and positive and negative predictive values were all 100% regardless of the EKG leads studied.
One patient developed negative T waves in Leads II, III, and V5; they resolved spontaneously in 50 s after the test-dose injection. No ventricular or supraventricular arrhythmia was observed in any patient throughout the study period.
One major finding of this study was that decreases in the T-wave amplitude of Leads II, I, III, and V5 were of similar magnitude in response to the simulated IV test dose containing epinephrine. In addition, the efficacy of the T-wave criterion was 100% and did not depend on the EKG leads studied in sevoflurane-anesthetized patients. 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 circumstances in our study. The clinical usefulness of the T-wave morphology as a diagnostic marker is further augmented by the fact that the magnitude of the T-wave reduction is similar over 0.5%–2% end-tidal sevoflurane (5), whereas typical hemodynamic changes associated with an IV test dose are affected by the depth of isoflurane anesthesia (4). The state of consciousness, the concomitant use of sedatives, and the subject’s age also appeared to have no effect on the temporal and maximum changes in T-wave amplitude (7,11). More importantly, when a smaller dose of the test dose is injected intravascularly, the sensitivity and specificity of the T-wave criterion are greater than those of the modified HR and SBP criteria, either alone or in combination, as might occur when the tip of a multiorifice epidural catheter migrates into the blood vessel (8,12). On the basis of these considerations, the T-wave criterion may be considered as a potentially reliable tool that might be applied to a variety of clinical situations.
Even though the exact mechanism of the decreased T-wave amplitude caused by the IV test dose remains undetermined in our study, the changes in T-wave amplitude of a 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. Epinephrine causes a reduction of serum potassium concentrations via β2-adrenoceptors (13,14). However, the influence of serum potassium changes on transient T-wave alterations was not clear in our study, because serial changes in serum potassium concentrations were not measured. Moreover, physical and psychological stress causes flattening and inversion of the T wave in humans (15–17), suggesting that T-wave amplitude may fluctuate depending on the degree of surgical stress. Therefore, ultimate validation of the reliability of the T-wave criterion requires a large-scale, prospective clinical trial during surgical procedures, especially when epidural blockade is wearing off.
The application of the hemodynamic and T-wave criteria requires some caution. First, patients taking cardiovascular medications were excluded from our study, because acute β-blockade reduces efficacy on the basis of the HR criterion in awake subjects (10). In addition, virtually absent HR and SBP responses, but significant decreases in T-wave amplitude, were reported after unintentional intravascular injection of an unknown amount of the epinephrine test dose in an elderly patient taking a calcium-channel blocker (12). The effects of antihypertensive medications, including calcium-channel blockers, on hemodynamic changes and the effectiveness of the IV test dose have not been addressed previously. Second, preexisting abnormalities of the EKG morphology, such as in patients taking digoxin, those with left ventricular hypertrophy, or those with a history of myocardial infarction, preclude application of the T-wave criterion (18). Finally, T-wave amplitude, per se, is significantly affected by both β-adrenergic agonists and antagonists (19). Whether the responsiveness of the T-wave morphology is altered in patients taking a β-blocker because of the IV test dose remains to be determined.
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 15 μg of epinephrine on the basis of the T-wave criterion (positive if ≥25% decrease in amplitude) in adult patients anesthetized with sevoflurane. However, our results should be confined to healthy subjects taking no cardiovascular medications and with normal EKG morphology.
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© 2002 International Anesthesia Research Society
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