Anesth Analg 2005;101:584-588
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000157571.00717.08
REGIONAL ANESTHESIA
Digital Skin Blood Flow as an Indicator for Intravascular Injection of Epinephrine-Containing Simulated Epidural Test Dose in Sevoflurane-Anesthetized Adults
Hany A. Mowafi, MB, Bch, MSc, MD
Department of Anesthesia, Faculty of Medicine, King Faisal University, Saudi Arabia
Address correspondence and reprint requests to Dr. Hany A. Mowafi, Anesthesiology Department, King Fahd University Hospital, PO Box 40081, Al-Khobar 31952, Saudi Arabia. Address e-mail to hany_mowafi{at}hotmail.com.
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Abstract
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I designed this study to determine the efficacy of heart rate (HR), systolic blood pressure (SBP), and digital skin blood flow (DSBF) in detecting intravascular injection after a simulated epidural test dose containing 15 µg of epinephrine in sevoflurane-anesthetized adults. In addition, the testing threshold using DSBF was derived. Eighty patients were randomized to receive either 0.5 minimum alveolar anesthetic concentration (MAC) sevoflurane or 1.0 MAC sevoflurane and nitrous oxide in oxygen (n = 40 for each sevoflurane concentration). Each group of patients was further randomized to receive either 3 mL of 1.5% lidocaine containing 15 µg of epinephrine IV or 3 mL of saline IV (n = 20 each). HR, SBP, and DSBF were monitored for 5 min after injection. By using the HR (positive if 
10 bpm increase) and SBP (positive if 15 mm Hg increase) criteria, a positive response rate to epinephrine was 95% for both variables during 0.5 MAC and 90% during 1.0 MAC sevoflurane anesthesia. Injection of the test dose resulted in peak DSBF decrease by 87% ± 8% and 81% ± 12% at 52 ± 10 and 53 ± 13 s in the sevoflurane 0.5 and 1.0 MAC groups, respectively. Positive DSBF criterion, as determined from peak increases during saline administration, was a decrease in DSBF 15%. Using this value, the sensitivity, specificity, positive predictive value, and negative predictive value were 100% in both sevoflurane groups. In conclusion, DSBF was superior to conventional hemodynamic criteria for detection of an intravascular injection of epidural test dose.
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Introduction
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The efficacy of an epinephrine-containing epidural test dose to detect an intravascular injection during general anesthesia has been questioned (1–3). This is mainly attributed to the decreased heart rate (HR) response to epinephrine in anesthetized patients and the need for invasive monitoring to detect the momentary increase in systolic blood pressure (SBP). Previous reports have shown that digital skin blood flow (DSBF) rapidly correlates with plasma epinephrine concentration (4,5). Thus, it may be used to detect an intravascular injection of an epinephrine test dose.
The aim of this study was to investigate whether changes in DSBF can be used as a new variable for detecting intravascular injection of an epinephrine-containing test dose in adults anesthetized with different concentrations of sevoflurane and to compare its reliability with the classical hemodynamic variables.
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Methods
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After local research committee approval and informed patient consent, 80 ASA physical status I or II patients, aged 18–50 yr, scheduled to undergo general anesthesia for elective surgery, were included in the study. Patients were excluded if they had diabetes mellitus or cardiovascular disease or were taking drugs affecting the cardiovascular system. A history of smoking was registered. Patients were randomly allocated into 2 equal groups (40 patients each) to receive either 0.5 minimum alveolar anesthetic concentration (MAC) sevoflurane or 1.0 MAC sevoflurane.
Patients were premedicated with 10 mg of diazepam orally 90 min preoperatively. Electrocardiographic HR and noninvasive oscillometric SBP were measured using an S/5 anesthesia monitor (Datex-Ohmeda, Helsinki, Finland). DSBF was measured using a laser Doppler flowmeter (Laserflo BPM2; Vasamedics Inc., Eden Prairie, MN). The device has an average response time of 200 ms and undergoes autocalibration. A plate-type probe was attached to the palmar side of the middle fingertip using double-faced adhesive tape. The hand contralateral to the site of SBP monitoring was used for DSBF monitoring and was wrapped in a towel to minimize heat loss.
Anesthesia was induced with fentanyl 2 µg/kg and propofol 2.5 mg/kg IV. Tracheal intubation was facilitated with vecuronium 0.1 mg/kg IV. Anesthesia was maintained with a stable end-tidal concentration of sevoflurane, according to the assignment groups and 60% nitrous oxide in oxygen. The lungs of patients were mechanically ventilated and minute volume was set to maintain end-tidal CO2 at 4–4.7 kPa. Fluid administration was standardized to 10 mL · kg–1 · h–1 of Ringer’s lactate solution and the ambient temperature was maintained at 25°–26°C.
When hemodynamic variables, DSBF, and end-tidal concentrations were stable for 5 min and at least 10 min had elapsed after anesthetic induction, each group of patients was further randomized to receive either 3 mL of isotonic saline (n = 20) or 3 mL of 1.5% lidocaine containing 15 µg of epinephrine IV (n = 20) as a simulated test dose via a peripheral IV catheter over 3 s, flushed with 10 mL of saline. After injection, SBP cycling was set to every minute for 5 min. S/5 collect software (Datex-Ohmeda) was used to collect HR, SBP, Spo2, and end-tidal concentrations every 10 s to a notebook PC. Collected data were later analyzed at 20-s intervals for HR and 1-min intervals for SBP. In addition, maximal HR and SBP responses were noted. DSBF data were collected every 20 s after injection by the attending anesthesiologist who was blinded to the injected test dose. All measurements were made before surgery with the patient in the supine position.
Based on a pilot study, sample size was selected to detect a maximal DSBF difference of 25% from the preinjection value with a type I error of 0.05 and type II error of 0.20. Positive HR and SBP responses to IV test dose were defined from previous reports (1) as HR increase 10 bpm and SBP increase 15 mm Hg. The 95% confidence intervals applicable to 99% of the general population (6) were calculated for DSBF after injection of saline. DSBF decreases more than these 95% confidence intervals were defined as positive response. Sensitivity (true positives/[true positives + false negatives]), specificity (true negatives/[true negatives + false positives]), positive predictive values (true positives/[true positives + false positives]), and negative predictive values (true negatives/[true negatives + false negatives]) were determined for HR, SBP, and DSBF.
Differences between groups in demographic data and baseline data were analyzed using one-way analysis of variance or 
2 test as appropriate. For comparison of different observations within and between the groups, data were analyzed by using repeated-measures analysis of variance, and differences were then calculated by Newman-Keuls test. Analysis was performed using Statistica software (Statsoft, Inc., Tulsa, OK). Data were presented as mean ± sd in the text and as mean ± 95% confidence intervals in the figures.
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Results
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There were no significant differences between groups with respect to age, weight, height, gender distribution, or the incidence of smoking. There were also no significant differences in the preinduction HR, SBP, and DSBF (Table 1). After induction of anesthesia and achievement of a steady sevoflurane concentration, SBP and HR decreased and DSBF increased significantly from preinduction values. There were, however, no significant differences between groups regarding preinjection (baseline) data.
IV injection of the test dose produced significant increases in HR (Fig. 1) and SBP (Fig. 2) in both groups. Maximal increases in HR in the sevoflurane 0.5 and 1.0 MAC groups were 16 ± 6 and 14 ± 5 bpm at 42 ± 6 and 53 ± 13 s after test dose injections, respectively. Maximal increases in SBP in sevoflurane 0.5 and 1.0 MAC groups were 26 ± 11 and 21 ± 9 mm Hg at 75 ± 27 and 81 ± 29 s after test dose injection, respectively. As shown in Figure 3, there were significant decreases in DSBF from the preinjection value between 20 and 280 s in the 0.5 MAC sevoflurane group and between 20 and 160 s in the 1.0 MAC sevoflurane group. The average largest percent decreases in the DSBF were 87% ± 8% and 81% ± 12% at 52 ± 10 and 53 ± 13 s after test dose injections in the 0.5 MAC and 1.0 MAC sevoflurane groups, respectively.
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Figure 1. Changes in heart rate (HR) after injection of the test dose containing 15 µg of epinephrine during 0.5 minimum alveolar anesthetic concentration (MAC) and 1.0 MAC sevoflurane and 60% nitrous oxide in oxygen (n = 20 for each sevoflurane concentration). Because HR was essentially unchanged after saline injection, these data are not presented. Vertical bars denote 0.95 confidence intervals. *Significant difference versus preinjection values (time 0).
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Figure 2. Changes in systolic blood pressure (SBP) after injection of the test dose containing 15 µg of epinephrine during 0.5 minimum alveolar anesthetic concentration (MAC) and 1.0 MAC sevoflurane and 60% nitrous oxide in oxygen (n = 20 for each sevoflurane concentration). Because SBP was essentially unchanged after saline injection, these data are not presented. Vertical bars denote 0.95 confidence intervals. *Significant difference versus preinjection values (time 0).
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Figure 3. Changes in digital skin blood flow (DSBF), expressed as percentage from the preinjection value, after injection of the test dose containing 15 µg of epinephrine during 0.5 minimum alveolar anesthetic concentration (MAC) and 1.0 MAC sevoflurane and 60% nitrous oxide in oxygen (n = 20 for each sevoflurane concentration). Because DSBF was essentially unchanged after saline injection, these data are not presented. Vertical bars denote 0.95 confidence intervals. *Significant difference versus preinjection values (time 0).
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After injection of saline, the peak percent decrease in DSBF was 3% ± 3% (mean ± sd) in both groups. Using this value, the 95% confidence interval for 99% of the population was calculated to be from –8% to 14% and thus DSBF criterion for identification of intravascular injection of the test dose should be a decrease of DSBF 15% from the preinjection value. The sensitivity, specificity, positive predictive value, and negative predictive value were all 100% based on DSBF criterion. In contrast, neither the HR changes nor the indirectly measured SBP changes were totally reliable in detection of intravascular injection of test dose (Table 2).
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Table 2. Sensitivity, Specificity, Positive and Negative Predictive Values Based on Hemodynamic and Skin Blood Flow Criteria
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Discussion
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One finding of this study was that neither the HR nor the indirectly measured SBP was 100% reliable in detecting an intravascular injection using the previously recognized criteria during sevoflurane anesthesia. A similar HR response had been reported by Tanaka and Nishikawa (7) during sevoflurane anesthesia and was attributed to the depressant effect of sevoflurane to maximal sinus rate responses to epinephrine. Although previous reports (1,7) have found SBP 15 mm Hg a reliable indicator for intravascular injection, this was not proven in the current study. The use of intermittent and noninvasive measurement of SBP may be the reason for the decreased sensitivity of our results.
Skin blood flow was measured with a laser Doppler flowmeter. In this method, a beam at a wavelength of 780 nm is delivered to tissues via a fiberoptic cable, and scattered in a random manner by moving erythrocytes. The scattered laser beam is processed digitally to derive tissue blood flow (8,9). Blood flow is expressed in mL · min–1 · 100 g–1 of tissue. In the present study, injection of the test dose resulted in significant decrease in DSBF after 20 seconds that was maintained for 280 s in the 0.5 MAC sevoflurane group and for 160 seconds in the 1.0 MAC sevoflurane group. The difference in the time that DSBF was decreased may be attributed to an inhibitory effect of the larger sevoflurane concentration on response to epinephrine (10).
Fingertips are ideal for measuring peripheral vascular responsiveness because of their density of arteriovenous anastomoses. Because these anastomoses are exclusively under 
-adrenergic innervation (11), DSBF monitoring may be advantageous in patients receiving ß-adrenergic blockers and those with reduced response to ß-adrenergic stimulation such as parturients (12) and the elderly (13). The strong maximal DSBF reduction after IV injection of 15 µg of epinephrine (87% and 81% in the sevoflurane 0.5 and 1.0 MAC sevoflurane groups, respectively) may indicate that a smaller dose of epinephrine will be enough to produce a positive response (15% DSBF decrease).
The major problem with DSBF monitoring is individual variations that are further exaggerated by smoking (14) and regional hypothermia. However, changes in DSBF can be quantified when each patient serves as his/her own control. Other measures taken were standardization of the anesthetic technique, attaching the measuring probe to the same finger, maintaining patients normothermic, and their hands covered with a blanket. Other concerns are the cost and availability of the monitor for routine use by anesthesiologists. Until a simple and inexpensive DSBF monitor is available, alternative safety steps, such as aspiration and incremental injection, associated with constant vigilance, remain the mainstay of safe epidural anesthesia (15).
In conclusion, unlike HR or indirectly measured SBP, DSBF (positive if there is a decrease 15%) was found to be a perfect marker of intravascular injection of an epinephrine-containing epidural test dose in sevoflurane anesthetized adults. Further studies are warranted to determine whether this novel criterion is still applicable in other patient populations, under different anesthetic techniques or with smaller doses of epinephrine.
The author thanks members of the anesthesia department of King Fahd Hospital, Al-Khobar, Saudi Arabia, for their collaboration and support.
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Footnotes
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Accepted for publication January 12, 2005.
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References
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Abstract
Introduction
