Anesth Analg 2005;101:1506-1511
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000181004.72325.D6
REGIONAL ANESTHESIA
The Efficacy of Plethysmographic Pulse Wave Amplitude as an Indicator for Intravascular Injection of Epinephrine-Containing Epidural Test Dose in 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 Hany A. Mowafi, Department of Anesthesia, 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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In this study, I evaluated the efficacy of plethysmographic pulse wave amplitude (PPWA) in detecting intravascular injection of a simulated epidural test dose containing 15 µg of epinephrine in adults during either sevoflurane or isoflurane inhaled anesthesia and compared its reliability to the classical heart rate (HR; positive if 
10 bpm) and systolic blood pressure (SBP; positive if 15 mm Hg) criteria. Eighty patients were randomized to receive either 1 mean alveolar anesthetic concentration of sevoflurane or 1 mean alveolar anesthetic concentration of isoflurane (n = 40 for each anesthesia group). Patients in each anesthesia group were 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 PPWA were monitored for 5 min after injection. Injection of the test dose resulted in peak PPWA decrease by 61% ± 17% and 58% ± 15% at 61 ± 12 s and 63 ± 13 s in the sevoflurane and isoflurane groups, respectively. Positive PPWA criterion, as determined from peak increases during saline administration, was a decrease in PPWA 10%. Using this value, the sensitivity, specificity, positive predictive, and negative predictive values of PPWA were 100% in both anesthetic groups. On the contrary, sensitivities of 85% and 95% were obtained based on HR criterion in the sevoflurane and isoflurane patients, respectively, and a sensitivity of 90% was obtained in both anesthesia groups on the basis of SBP criterion. In conclusion, PPWA is a reliable alternative to conventional hemodynamic criteria for detection of an intravascular injection of epidural test dose.
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Introduction
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Combined epidural and general anesthesia is a popular technique for providing anesthesia and postoperative analgesia to patients undergoing surgery (1,2). To avoid the potentially life-threatening cardiovascular and central nervous toxicity associated with intravascular injection of large amounts of local anesthetic solutions, an epidural test dose containing 15 µg of epinephrine is used (3–5). However, the hemodynamic criteria of positive intravascular injection of the epinephrine-containing test dose may be unreliable during anesthesia (6–8). This is mainly because of the decreased heart rate (HR) response to epinephrine in anesthetized patients and the need for invasive monitoring to detect the peak increases in systolic blood pressure (SBP).
Although a previous study demonstrated that digital skin blood flow, as measured by a laser Doppler flowmeter, is a reliable marker for an intravascular test-dose injection during anesthesia (9), the cost and availability of laser Doppler flow meters may limit the routine use of this diagnostic tool. However, plethysmographic pulse wave monitoring is readily available for routine use by anesthesiologists. Its amplitude indicates blood volume changes in the fingertips (10) and, thus, may be used for detection of the intravascular test-dose injection. Additionally, because inhaled anesthetics differ in their depressant actions and hemodynamic responses to catecholamines, the efficacy of the epinephrine-containing test dose may vary under the influence of different anesthetics (11).
The aim of this study was to investigate whether changes in plethysmographic pulse wave amplitude (PPWA) can be used as a new criterion for detecting intravascular injection of an epinephrine-containing test dose in adults under stable sevoflurane or isoflurane anesthesia and to compare its reliability to the classical hemodynamic criteria.
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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 old, scheduled to undergo general anesthesia for elective surgery, were included in the study. Exclusion criteria included a history of smoking, diabetes mellitus, cardiovascular diseases, or use of medications affecting the cardiovascular system. Patients were randomly allocated using an online research randomizer (http://www.randomizer.org) into 2 equal groups (40 patients each) to receive either 1 mean alveolar anesthetic concentration (MAC) of sevoflurane or 1 MAC of isoflurane.
Patients were premedicated with 10 mg of diazepam orally 90 min before surgery. Electrocardiographic HR, noninvasive oscillometric SBP, and PPWA were measured using an S/5 anesthesia monitor (Datex-Ohmeda, Helsinki, Finland), and the data were collected using Datex-Ohmeda S/5 collect software every 10 s. The S/5 collect reads data through the monitor serial port connected to a notebook personal computer. The oximeter probe used to monitor the plethysmographic pulse wave was attached to the middle fingertip of the hand contralateral to the site of SBP monitoring and was wrapped in a towel to minimize heat loss and contamination with ambient light. The plethysmographic pulse wave displayed on the monitor is derived from the infrared signal of the sensor. The display scale or the amplitude factor is automatically detected and set to optimum when the probe is first connected to the patient. From that moment, the gain is fixed, and any changes in the amplitude reflect the pulsatile blood flow in the finger. The PPWA is measured in percentage from the light that passed the tissue at a certain heart rhythm. The formula used is:
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where (Imax) is the maximum intensity of light transmitted to the receiving diode after absorption by tissues and nonpulsatile blood in the finger and (
I) is the difference between maximum and minimum transmitted light caused by the additional light absorbed by the pulsatile blood.
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 1 MAC end-tidal concentration of sevoflurane or isoflurane according to the assignment groups in addition to 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. End-tidal gas concentrations were measured with S/5 compact airway module M-CAiOVX attached to the S/5 anesthesia monitor (Datex-Ohmeda). Fluid administration was standardized to 10 mL · kg–1 · h–1 of Ringer’s lactate solution, and the ambient temperature was maintained at 25°C-26°C.
When hemodynamic variables, PPWA, and end-tidal concentrations were stable for 5 min and at least 10 min had elapsed after the 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 for 3 s flushed with 10 mL of saline. After the injection, blood pressure cycling was set to every minute for 5 min. S/5 collect software (Datex-Ohmeda) was used to collect HR, SBP, PPWA, Spo2, and end-tidal concentrations every 10 s (Fig. 1). Collected data were later analyzed at 20-s intervals for HR and PPWA and at 1-min intervals for SBP. In addition, maximal HR, SBP, and PPWA responses were noted. Anesthesia was conducted and data were collected by the attending anesthesiologist who was blinded to the injected test dose. All measurements were made with the patient in the supine position before surgery.
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Figure 1. Example of the data collected by Datex-Ohmeda S/5 collect software for one case during sevoflurane anesthesia after an injection of the simulated test dose. The waveforms are for electrocardiogram (ECG) and plethysmographic (pleth) pulse wave. The trends are for the heart rate (HR), noninvasive systolic blood pressure (SBP), end-tidal (Et) sevoflurane, and plethysmographic pulse wave amplitude (PPWA), which is presented using integer arithmetic so that the reading of 100 is 1% of the PPWA.
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Power analysis was based on a pilot study of 10 patients (5 in each anesthesia group). More than 15 patients were required in each group during sevoflurane anesthesia, and more than 17 patients were required in each group during isoflurane anesthesia to detect a maximum PPWA difference of 25% from the preinjection values with a type I error of 0.05 and type II error of 0.20. Positive HR and SBP responses to the IV test dose were prospectively defined from previous reports (6) as a HR increase of 10 bpm and a SBP increase of 15 mm Hg within 2 min of administration. Ninety-five percent confidence intervals applicable to 99% of the general population (12) were calculated for PPWA after the injection of saline in each anesthetic group. PPWA increases more than 95% tolerance limits were defined as positive criteria for detection of an intravascular injection of the test dose. 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 PPWA variables.
Data were tested for normal distribution using the Kolmogorov-Smirnov test. Differences between groups in demographic data and baseline values of hemodynamic variables, and PPWA 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 first analyzed by repeated-measures analysis of variance, and differences were then calculated by post hoc testing (Newman-Keuls test). Fisher exact test was used to compare sensitivities between groups. Analysis was performed using Statistica software version 6.0 for windows (Statsoft, Inc., Tulsa, OK). Data were presented as mean ± sd in the text and Table 1 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, and sex distribution. There were also no significant differences in the preinduction HR, SBP, and PPWA (Table 1). After the induction of anesthesia and achievement of a steady anesthetic concentration, SBP and HR decreased, whereas PPWA 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. 2) and SBP (Fig. 3) in both groups. Maximal increases in HR in the sevoflurane and isoflurane groups were 14 ± 6 bpm and 18 ± 8 bpm at 47 ± 14 s and 48 ± 16 s after test-dose injections, respectively. Maximal increases in SBP in sevoflurane and isoflurane groups were 19 ± 8 mm Hg and 20 ± 7 mm Hg at 84 ± 30 s and 93 ± 31 s after test-dose injections, respectively. As shown in Figure 4, there were significant decreases in PPWA from the preinjection value between 40 and 200 s in the sevoflurane group and between 20 and 120 s in the isoflurane group. The average largest percent decreases in the PPWA were 61% ± 17% and 58% ± 15% at 61 ± 12 s and 63 ± 13 s after test-dose injections in the sevoflurane and isoflurane groups, respectively.
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Figure 2. Changes in heart rate (HR) after injection of the test dose containing 15 µg of epinephrine or isotonic saline during sevoflurane and isoflurane anesthesia (n = 20 for each group). Vertical bars denote 0.95 confidence intervals. *Significant difference versus preinjection values (time 0).
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Figure 3. Changes in systolic blood pressure (SBP) after injection of the test dose containing 15 µg of epinephrine or isotonic saline during sevoflurane and isoflurane anesthesia (n = 20 for each group). Vertical bars denote 0.95 confidence intervals. *Significant difference versus preinjection values (time 0).
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Figure 4. Changes in plethysmographic pulse wave amplitude (PPWA), expressed as percent from the preinjection value, after injection of the test dose containing 15 µg of epinephrine or isotonic saline during sevoflurane and isoflurane anesthesia (n = 20 for each group). Vertical bars denote 0.95 confidence intervals. *Significant difference versus preinjection values (time 0).
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After the injection of saline, the peak percent decrease in PPWA was 2% ± 2% (mean ± sd) in both groups. Using this value, the 95% confidence interval for 99% of the population was calculated to be from –5% to 9%, and thus, PPWA criterion for identification of intravascular injection of the test dose should be a decrease of PPWA 10% from the preinjection value. The sensitivity, specificity, positive predictive value, and negative predictive value were all 100% based on PPWA criterion. In contrast, neither the HR nor the indirectly measured SBP changes were totally reliable in detection of intravascular injection of test dose (Table 2). The two-tailed Fisher exact test resulted in P values of 0.23 and 1.0 for the comparison of the sensitivities between the PPWA and HR criteria in the sevoflurane and isoflurane groups, respectively and a P value of 0.48 for the comparison of the sensitivities of PPWA and SBP criteria in both anesthetic groups. Additionally, there were no statistically significant differences between the two anesthetics in sensitivities based on all the criteria measured.
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Table 2. Sensitivity, Specificity, Positive, and Negative Predictive Values Based on Hemodynamic and Plethysmographic Pulse Wave Amplitude Criteria
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Discussion
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One of the major findings in the present study was that, using the previously recognized criteria for positive response during anesthesia, neither the HR nor the indirectly measured SBP were 100% reliable in detecting an intravascular injection of an epinephrine-containing test dose during stable 1 MAC of sevoflurane or isoflurane anesthesia. The study also introduced PPWA as a new criterion for detecting intravascular injection of the test dose and demonstrated 100% efficacy based on this criterion regardless of the inhaled anesthetic used.
Failure to demonstrate 100% efficacy on the basis of the conventional hemodynamic criteria indicates a limitation of the HR and noninvasive SBP responses as markers for detecting an intravascular test-dose injection. This is in agreement with previous reports (9,11), which found the HR response not reliable in detecting intravascular injection during sevoflurane anesthesia. A previous study (13) showed that a HR increase 10 bpm was associated with a 100% sensitivity and specificity under end-tidal isoflurane concentration 
1% and that the HR responses to test-dose injection were depressed in a concentration-dependent manner. The reduced HR response to test-dose injection during isoflurane anesthesia in the present study may have been due to the larger concentration of isoflurane administered (1.2%). As with previous reports (9), the use of intermittent and noninvasive measurement of SBP decreased its reliability to detect intravascular injection because the short-lived SBP increases may easily be missed.
Photoelectric plethysmography, a technique first described decades ago (14) and almost always routinely available on the operating room monitors (15), is not fully used in clinical practice (16). Studies comparing PPWA and laser Doppler measurements, thermography, or forearm flow measurements have demonstrated correlation in the dynamic changes between PPWA and digital blood flow (17,18).
Changes in finger PPWA correspond to changes in the blood volume pulsations and depend on the distensibility of the vascular wall and the intravascular pulse pressure. Usually, the effect of autonomic impulses upon distensibility is so strong that it predominates over the opposite effect of pulse pressure. Decreases in PPWA connected with pain and other stressful stimuli are caused by vasoconstriction of the finger arterial bed rather than changes in the pulse pressure (19). As with endogenous catecholamines, drugs cause a predictable reduction in PPWA (20). In the present study, injection of the epinephrine-containing test dose resulted in significant decreases in PPWA from 20 to 140 seconds in the isoflurane group and from 40 to 200 seconds in the sevoflurane group. The difference in the time the PPWA was decreased may be attributed to a more potent inhibitory effect of isoflurane on the response to epinephrine (21). The strong maximal PPWA reduction after IV injection of 15 µg of epinephrine (61% and 58% in the sevoflurane and isoflurane groups, respectively) may indicate that a smaller dose of epinephrine will be enough to produce a positive response (10% PPWA decrease).
Several measures were taken in the present study to eliminate sources of error with finger plethysmographic monitoring (10). Patients who smoked, those with vascular disease, or taking medication that affects vascular resistance were excluded. Anesthetic technique, drugs, and monitoring site were standardized. Patients were maintained normothermic, and their hands were covered with a dark blanket to avoid regional hypothermia and contamination with ambient light. All measurements were made with the patient in the supine position with the transducer at the level of the heart. Importantly, to avoid individual variations in absorption, scattering and reflection of the emitted light, only within-subject changes in the PPWA, were reported as every patient served as his or her control.
Our study must be interpreted with some caution. First, our results apply only to healthy young adults undergoing general anesthesia with either sevoflurane or isoflurane. Other patient populations, such as the elderly, those with vascular disease, those receiving vasoactive drugs, or those receiving different anesthetics may have altered plethysmographic pulse wave responses and thus require separate determination of the response criteria and the reliability profile. Second, our study design was based on the injection of the full test dose of IV epinephrine. In actual clinical practice, however, only a fractional dose may be inadvertently injected IV. Thus, a dose-response study is required to determine the minimum effective dose of epinephrine required to elicit 100% reliability based on the PPWA criterion. Third, although this study showed that conventional hemodynamic criteria were imperfect markers of test dose injection, and that PPWA was a reliable indicator, it failed to demonstrate that the PPWA criterion was more effective than the HR or the noninvasive SBP criteria. This is because of the smaller number of patients assigned in our study (type II error). Retrospective power analysis of our data revealed that at least 48 and 150 patients would be required to provide a power >0.8 (P = 0.5) for detecting a statistically significant difference in sensitivities between the PPWA and HR criteria in the sevoflurane and isoflurane groups, respectively. Similarly, 74 patients would be required for detecting statistically significant differences in sensitivities between PPWA and noninvasive SBP criteria in both anesthetic groups. Finally, the ability of the attending anesthesiologist to detect a 10% decrease in the PPWA displayed on the oscilloscope was not tested in the present study because this should be addressed in a blinded, prospective manner. However, the addition of numerical values indicating the PPWA, termed the Perfusion Index (22), to new pulse oximeters will enhance the clinical applicability of the PPWA criterion.
In conclusion, unlike HR or noninvasive SBP, PPWA was found to be a reliable indicator of intravascular injection of an epinephrine-containing epidural test dose in anesthetized adults. Further studies are warranted to determine whether this novel method is applicable to other patient populations, under different anesthetic techniques, or with smaller doses of epinephrine.
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Footnotes
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Accepted for publication May 12, 2005.
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References
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- Dunet F, Pfister Ch, Deghmani M, et al. Clinical results of combined epidural and general anesthesia procedure in radical prostatectomy management. Can J Urol 2004;11:2200–4.[Medline]
- Dahl JB, Daugaard JJ, Rasmussen B, et al. Immediate and prolonged effects of pre- versus postoperative epidural analgesia with bupivacaine and morphine on pain at rest and during mobilisation after total knee arthroplasty. Acta Anaesthesiol Scand 1994;38:557–61.[Web of Science][Medline]
- Lee PK, Kim JM. Lumbar epidural blocks: a case report of a life-threatening complication. Arch Phys Med Rehabil 2000;81:1587–90.[Web of Science][Medline]
- Mulroy MF, Norris MC, Liu SS. Safety steps for epidural injection of local anesthetics: review of literature and recommendations. Anesth Analg 1997;85:1346–56.[Web of Science][Medline]
- Guinard JP, Mulroy MF, Carpenter RL, Knopes KD. Test doses: optimal epinephrine content with and without beta-adrenergic blockade. Anesthesiology 1990;73:386–92.[Web of Science][Medline]
- Takahashi S, Tanaka M. Reduced efficacy of simulated epidural test dose in sevoflurane-anesthetized adults. Can J Anaesth 1999;46:433–8.[Web of Science][Medline]
- Tanaka M, Yamamoto S, Ashimura H, et al. Efficacy of an epidural test dose in adult patients anesthetized with isoflurane: lidocaine containing 15 micrograms epinephrine reliably increase arterial blood pressure, but not heart rate. Anesth Analg 1995;80:310–4.[Abstract]
- Liu SS, Carpenter RL. Hemodynamic responses to intravascular injection of epinephrine-containing epidural test doses in adults during general anesthesia. Anesthesiology 1996;84:81–7.[Web of Science][Medline]
- Mowafi HA. Digital skin blood flow as an indicator for intravascular injection of epinephrine-containing simulated epidural test dose in sevoflurane-anesthetized adults. Anesth Analg. 2005;101:584–8.[Abstract/Free Full Text]
- Blanc FB, Haig M, Troli M, Sauve B. Computerized photoplethysmography of the finger. Can J Anaesth 1993;40:271–8.[Web of Science][Medline]
- Tanaka M, Toshiaki N. A comparative study of hemodynamic and T-wave criteria for detecting intravascular injection of the test dose (epinephrine) in sevoflurane anesthetized adults. Anesth Analg 1999;89:32–6.[Abstract/Free Full Text]
- Glantz SA. Confidence Intervals for the entire population. In: Glantz SA, ed. Primer of biostatistics. Third ed. New York: Mcgraw-Hill, 1992;212–7.
- Tanaka M, Takahashi S, Kondo T, Matsumiya N. Efficacy of simulated epidural test dose in adult patients anesthetized with isoflurane: a dose response study. Anesth Analg 1995;81:987–92.[Abstract]
- Hertzman AB. The blood supply of various skin areas as estimated by the photoelectric plethysmograph. Am J Physiol 1938;124:328–40.[Free Full Text]
- Murray WB, Foster PA. The peripheral pulse wave: information overlooked. J Clin Monit 1996;12:365–77.[Web of Science][Medline]
- Eichhorn JH, Cooper JB, Cullen DJ, et al. Standards for patient monitoring during anesthesia at Harvard Medical School. JAMA 1986;256:1017–20.[Abstract/Free Full Text]
- Marszalek A. The use of selected methods in assessing peripheral circulation of blood. Med Pr 2000;51:299–309.[Medline]
- Alam TA, Seifalian AM, Baker D. A review of methods currently used for assessment of in vivo endothelial function. Eur J Vasc Endovasc Surg 2005;29:269–76.[Web of Science][Medline]
- Dorlas JC, Nijboer JA. Photo-electric plethysmography as a monitoring device in anesthesia. Br J Anaesth 1985;57:524–30.[Abstract/Free Full Text]
- Hoffman BB, Lefkowitz RJ. Chatecholamines and sympathomimetic drugs. In: Gilman AG, Hardman JG, Limbird LE, et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. New York: Pergamon Press, 1996:199–284.
- Akata T, Kodama K, Takahashi S. Volatile anaesthetic actions on norepinephrine-induced contraction of small splanchnic resistance arteries. Can J Anaesth 1995;42:1040–50.[Web of Science][Medline]
- Hager H, Reddy D, Kurz A. Perfusion index: a valuable tool to assess changes in peripheral perfusion caused by sevoflurane. Anesthesiology 2003;99:A–593.
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Abstract
Introduction
