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PEDIATRIC ANESTHESIOLOGY

Plethysmographic Pulse Wave Amplitude Is an Effective Indicator for Intravascular Injection of Epinephrine-Containing Epidural Test Dose in Sevoflurane-Anesthetized Pediatric Patients

From the Department of Anesthesiology, Faculty of Medicine, King Faisal University, Saudi Arabia.

Address correspondence and reprint requests to Dr. Hany A. Mowafi, Department of Anesthesiology, King Fahd University Hospital, PO Box 40081, Al-Khobar 31952, Saudi Arabia. Address e-mail to hany_mowafi{at}hotmail.com.

Abstract

BACKGROUND: Plethysmographic pulse wave amplitude (PPWA) was effective in detecting intravascular injection of epidural test dose with 100% sensitivity and specificity in adults. We evaluated the efficacy of PPWA in detecting intravascular injection of a simulated epidural test dose during sevoflurane anesthesia in pediatric patients.

METHODS: Eighty infants and children were randomized to receive either 0.5 minimal alveolar concentration (MAC) or 1 MAC sevoflurane and nitrous oxide in oxygen. Patients in each anesthesia group were further randomized to receive either 0.1 mL/kg of 1% lidocaine with 1:200,000 epinephrine (0.5 µg/kg of epinephrine) IV to simulate the intravascular injection of epidural test dose or saline. Heart rate (HR), systolic blood pressure (SBP), and PPWA were monitored for 5 min after injection. A positive test response was defined as HR increase 10 bpm, SBP increase 15 mm Hg, and PPWA decrease 10%.

RESULTS: Injecting the test dose resulted in an average maximum PPWA decrease by 69% ± 18% and 58% ± 14% at 79 ± 22 and 80 ± 19 s in the 0.5 MAC and 1 MAC sevoflurane groups, respectively. The sensitivity, specificity, positive predictive, and negative predictive values for PPWA were 100% in both sevoflurane groups, whereas by using HR and SBP criteria, the sensitivity was 90% and 95% respectively during 0.5 MAC sevoflurane anesthesia and 85% for both during 1 MAC sevoflurane anesthesia.

CONCLUSION: PPWA is effective for detection of an intravascular injection of a simulated epidural epinephrine-containing test dose in pediatric patients.

In pediatric patients, epidural or caudal techniques are usually performed under general anesthesia.1,2 Inadvertent systemic injection is a known complication of epidural or caudal analgesia in this age group. If unrecognized, local anesthetic toxicity may result in seizures, arrhythmias, cardiovascular collapse, and death. The incidence of inadvertent intravascular injection of local anesthetics ranges between 0.4% and 5.6% of epidural trials in children.3,4 Therefore, a regimen that predicts intravascular injection with 100% sensitivity and specificity is required.5,6 Changes in heart rate (HR), systolic blood pressure (SBP), and T-wave amplitude of the electrocardiogram in response to epinephrine-containing test dose have been tried.5–8 However, the available reports denote an inconsistent sensitivity and specificity with the conventional hemodynamic variables, particularly in the presence of inhaled anesthetics. This is mainly because of the decreased HR response to epinephrine in anesthetized patients and the need for invasive monitoring to detect the peak increases in arterial blood pressure (BP).9

Reduction of plethysmographic pulse wave amplitude (PPWA) is a reliable indicator for intravascular injection of an epidural epinephrine-containing test dose in adults during anesthesia.10 However, it remains to be seen whether similar changes in PPWA could be elicited by an IV test dose in anesthetized children. Therefore, this prospective, randomized, double-blind study was designed to evaluate the efficacy of the PPWA response as a marker to a simulated test dose consisting of lidocaine and epinephrine in pediatric patients under stable sevoflurane anesthesia.

METHODS

After local research committee approval and informed parental consent for each patient, 80 ASA physical status I children aged 0.5–12 yrs with normal sinus rhythm scheduled to receive general anesthesia for elective surgery were included in the study.

Patients were randomly allocated using an online research randomizer (http://www.randomizer.org/) into two equal groups (40 patients each) to receive 0.5 minimal alveolar concentration (MAC) or 1 MAC of sevoflurane and 60% nitrous oxide in oxygen. Children were premedicated with oral midazolam 0.5 mg/kg 30 min before the induction of anesthesia. Electrocardiographic HR, noninvasive automatic 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’s serial port connected to a notebook personal computer. An Oxitip® Wrap Sensor (Datex-Ohmeda, Helsinki, Finland) was used to monitor the plethysmographic pulse wave and was attached to the thumb of the hand contralateral to the site of BP monitoring and was wrapped with a towel to minimize heat loss and contamination with ambient light. The PPWA principle has been described previously.10

Anesthesia was induced with a facemask using 60% nitrous oxide in oxygen and incremental sevoflurane until the patient was unconscious. Inhaled anesthesia via a facemask was continued using assisted then controlled ventilation. All patients received 1 µg/kg fentanyl IV. Lactated Ringer’s solution was administered at a rate of 5 mL·kg^–1·h^–1 throughout the study period. After inserting a laryngeal mask, ventilation was controlled to maintain an end-tidal (ET)co₂ tension between 30 and 35 mm Hg, and an ET anesthetic concentration of 0.5 or 1.0 MAC of sevoflurane and 60% nitrous oxide in oxygen. Rectal temperature was maintained between 36°C and 37°C.

When hemodynamic variables, PPWA, and ET anesthetic and CO₂ concentrations were stable for 5 min and at least 10 min had elapsed after the anesthetic induction, each group of patients was further randomly allocated to receive either 0.1 mL/kg of isotonic saline (n = 20) or 0.1 mL/kg of 1% lidocaine with 1:200,000 epinephrine (0.5 µg/kg of epinephrine) IV to simulate the intravascular injection of an epidural test dose via a peripheral IV catheter for 5 s flushed with 10 mL of saline. After the injection, BP was measured once per minute for 5 minutes. S/5 collect software (Datex-Ohmeda) was used to collect HR, SBP, PPWA, Spo₂, and ET concentrations every 10 s. 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. Positive HR, SBP, and PPWA responses to the IV test dose were prospectively defined from previous reports7,10 as a HR increase of 10 bpm, a SBP increase of 15 mm Hg and a PPWA decrease 10% after simulated test dose administration. 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. 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.

Power analysis was based on a pilot study. Fifteen patients were required in each group during sevoflurane 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 0.10.

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’s exact test was used to compare sensitivities between groups. Analysis was performed using Statistica software version 7.0 for windows (Statsoft, Tulsa, OK). Data were presented as mean ± sd in the text and tables and as mean ± 95% confidence intervals in the figures.

RESULTS

There were no significant differences between groups with respect to age and weight. There were also no significant differences in the control (before injection of the test dose) HR, SBP, and PPWA values (Table 1).

IV injection of the test dose produced significant increases in HR (Fig. 1) and SBP (Fig. 2) in both anesthesia groups. Maximal increases in HR in the 0.5 MAC and 1 MAC sevoflurane groups were 29 ± 18 and 22 ± 13 bpm at 36 ± 14 and 35 ± 13 s after test dose injections, respectively. Maximal increases in SBP in 0.5 MAC and 1 MAC sevoflurane groups were 28 ± 7 and 24 ± 14 mm Hg at 78 ± 28 and 84 ± 35 s after test dose injection, respectively. As shown in Figure 3 there were significant decreases in PPWA from the preinjection (baseline) values between 40 and 200 s in the 0.5 MAC sevoflurane group and between 40 and 140 s in the 1 MAC sevoflurane group. The percent PPWA reduction was more in patients who received 0.5 MAC sevoflurane and this reached statistical significance at 140–160 s The average largest percent decreases in the PPWA were 69% ± 18% and 58% ± 14% at 79 ± 22 and 80 ± 19 s after test dose injections in the 0.5 MAC and 1 MAC sevoflurane groups, respectively. After injection of saline the study variables were essentially unchanged in both anesthesia groups.

View larger version (22K): [in this window] [in a new window]   Figure 1. Changes in heart rate (HR), expressed as change from the preinjection value, after injection of the test dose consisting of 1% lidocaine with 1:20,000 epinephrine (epinephrine 0.5 µg/kg) or saline during 0.5 minimal alveolar anesthetic concentration (MAC) and 1 MAC sevoflurane and 60% nitrous oxide in oxygen anesthesia in infants and children (n = 20 for each group). Vertical bars denote 0.95 confidence intervals. *A significant difference versus preinjection values (time 0).

View larger version (17K): [in this window] [in a new window]   Figure 2. Changes in systolic blood pressure (SBP), expressed as change from the preinjection value, after injection of the test dose consisting of 1% lidocaine with 1:20,000 epinephrine (epinephrine 0.5 µg/kg) or saline during 0.5 minimal alveolar anesthetic concentration (MAC) and 1 MAC sevoflurane and 60% nitrous oxide in oxygen anesthesia in infants and children (n = 20 for each group). Vertical bars denote 0.95 confidence intervals. *A significant difference versus preinjection values (time 0).

View larger version (22K): [in this window] [in a new window]   Figure 3. Changes in plethysmographic pulse wave amplitude (PPWA), expressed as % change from the preinjection value, after injection of the test dose consisting of 1% lidocaine with 1:20,000 epinephrine (epinephrine 0.5 µg/kg) or saline during 0.5 minimal alveolar anesthetic concentration (MAC) and 1 MAC sevoflurane and 60% nitrous oxide in oxygen anesthesia in infants and children (n = 20 for each group). Vertical bars denote 0.95 confidence intervals. *A significant difference versus preinjection values (time 0). #A significant difference versus 0.5 MAC Sevoflurane group.

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’s exact test resulted in P values of 0.48 and 1.0 for the comparison of the sensitivities between the PPWA and HR criteria and the PPWA and SBP criteria, respectively, in the 0.5 MAC sevoflurane group, and a P value of 0.23 for the comparison of the sensitivities of PPWA and both conventional criteria in the 1.0 MAC sevoflurane group. Additionally, there were no statistically significant differences between the two sevoflurane groups in sensitivities based on all the criteria measured.

DISCUSSION

The main finding in the present study was that percent PPWA response criterion (a decrease 10%) is a reliable marker for detecting the intravascular injection of an epinephrine-containing epidural test dose during stable 0.5 MAC or 1 MAC sevoflurane anesthesia in pediatric patients. It achieved 100% (CI 83%–100%) sensitivity and specificity.

In this study, HR criterion was not 100% reliable in detecting intravascular injection of a simulated test dose containing epinephrine during sevoflurane anesthesia at 0.5 MAC or 1 MAC with nitrous oxide groups in children (sensitivity was 90% and 85%, respectively). This finding could be attributed to a direct depression of the sinoatrial node by sevoflurane.11 This decreased sensitivity of the HR criterion was reported by Kozek-Langenecker et al.12 and Burstal et al.13 who found a sensitivity of 71% and 46% respectively in children anesthetized with 1 MAC sevoflurane and nitrous oxide after IV injection of a simulated test dose. The marked decrease in sensitivity in the later study could be attributed to the speed of injection which was within 15 s while the duration of injection was 5 s in our study and it was not declared in the Kozek-Langenecker et al.12 study. The faster speed of injection may have resulted in a higher peak level of epinephrine.13 However, further studies are required to explore the effect of speed of injection of the epinephrine-containing epidural test dose on the peak plasma epinephrine levels, and thus on the reliability of the positive response criteria.

The sensitivity of SBP criterion in the present study was 95% and 85% for detection of IV epinephrine during 0.5 MAC and 1 MAC sevoflurane groups, respectively. Previous studies showed variable results.7,12,13 Kozek-Langenecker et al.12 demonstrated that SBP increased by 15 mm Hg in 95% of sevoflurane-anesthetized children after a simulated IV epidural test dose similar to our study.12 Additionally, Tanaka and Nishikawa7 and Burstal et al.13 showed that this criterion was achieved in 67% and 66%, respectively. As previously explained, the speed of injection may be responsible for these differences. The use of intermittent and noninvasive measurement of BP decreased its reliability to detect intravascular injection because the temporary SBP increases may be easily missed.7 Failure to demonstrate 100% efficacy of the HR and noninvasive SBP criteria as markers for confirming intravascular test dose injection in children is a limitation of these conventional hemodynamic responses.

On the other hand, PPWA provided an efficient indication for intravascular injection of epinephrine in children under sevoflurane anesthesia. All infants and children receiving sevoflurane anesthesia met the previously described PPWA criterion10 (a decrease 10%) in response to direct IV injection of epinephrine without false-positive responses after saline injection, resulting in 100% sensitivity, specificity, and positive and negative predictive values. In the present study, injection of the epinephrine-containing test dose resulted in significant decreases in PPWA from 40 to 200 s in the 0.5 MAC group and from 40 to 140 s in the 1 MAC sevoflurane group. The difference in the timing in which the PPWA decreased may be attributed to a stronger inhibitory effect of higher sevoflurane concentration on the response to epinephrine.14 The strong maximal PPWA reduction after IV injection of epinephrine (69% and 58% in the 0.5 MAC and 1 MAC sevoflurane groups, respectively) may indicate that a smaller dose of epinephrine will be enough to produce 10% reduction. Additionally, sevoflurane, 0.5 MAC, could increase the probability of detection of an accidental intravascular injection of epinephrine-containing solutions in clinical practice compared with 1 MAC.

It is essential to state that the sensitivity and specificity of PPWA were 100% without atropine pretreatment; atropine administration in particular is not routine in patients anesthetized with sevoflurane. This increases the strength of PPWA criterion as a marker for detecting intravascular injection of epinephrine-containing epidural test dose. However, the fact that our patients did not receive atropine may have had a negative impact on sensitivity and specificity of HR/BP changes. This could be attributed to the effect of atropine pretreatment on enhancing both the β-adrenergic receptor activity and baroreceptor sensitivity to sympathetic stimulation.13

Pulse oximeters display oxygen saturation and HR values, in addition to a photoplethysmographic waveform that is available on most operating room monitors, albeit, under-utilized in clinical practice. Finger PPWA reflects a combination of blood volume and flow changes in skin microcirculation.15,16 It depends 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.15,16 Several studies showed that the PPWA of the fingers is very sensitive to changes in vascular tone and sympathetic stimulation. Once a baseline measurement has been established, the PPWA can be followed as a gauge of sympathetic tone.17–19 Decreases in PPWA associated with pain and other stressful stimuli are due to sympathetic stimulation leading to catecholamine release.20 As with endogenous catecholamines, drugs cause a predictable reduction in PPWA.21

Several measures were taken in the present study to eliminate sources of error with finger plethysmographic monitoring.22 Anesthetic technique, drugs and monitoring site were standardized. Patients were maintained normothermic and their hands covered with a dark blanket to avoid regional hypothermia and contamination with ambient light. The PPWA sensor was wrapped initially at the optimal application pressure to obtain the maximum amplitude. All measurements were made 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 own control. However, the addition of numerical values indicating the PPWA, the "Perfusion Index,"23 to new pulse oximeters will enhance the clinical applicability of the PPWA criterion.

Some limitations are present in the current work. First, although this study showed that PPWA achieved 100% sensitivity and specificity in detecting the intravascular injection of an epinephrine-containing epidural test dose, it failed to demonstrate that the PPWA criterion was more effective than the conventional hemodynamic 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 74 and 152 patients would be required to provide a power >0.8 (P = 0.5) for detecting a statistically significant difference in sensitivities between PPWA and both HR and noninvasive SBP, respectively, in the 0.5 MAC sevoflurane group. Similarly, 48 patients would be required for detecting statistically significant differences in sensitivities between PPWA and both conventional criteria in the 1 MAC sevoflurane group. Second, the simulated test dose in the present study was injected with patients in the supine position. Further studies are required to show if PPWA will have the same sensitivity and specificity if injections are made with patients in the lateral position, as usually performed during epidural injections under general anesthesia. Additionally, our study concerned only pediatric patients under sevoflurane anesthesia, and those receiving different anesthetics may have a different PPWA response and thus require further study of the reliability of PPWA criterion. Also, a smaller epinephrine dose than that used in our work may be inadvertently injected IV during clinical practice. Therefore, a dose-response study is required to determine the minimum effective dose of epinephrine required to elicit 100% consistency of the PPWA criterion. The age range in the present study is wide and subdividing patients into more specific age groups may result in different changes.

In conclusion, PPWA is an effective indicator of intravascular injection of an epinephrine-containing epidural test dose under sevoflurane anesthesia in pediatric patients. Further studies are warranted to determine whether this criterion is still valid under diverse anesthetic techniques or with smaller doses of epinephrine.

Footnotes

Accepted for publication April 29, 2008.

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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 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 (1) Citing Articles via Google Scholar Google Scholar Articles by Mowafi, H. A. Articles by Al-Metwalli, R. R. Search for Related Content PubMed PubMed Citation Articles by Mowafi, H. A. Articles by Al-Metwalli, R. R. Related Collections Complications Patient Safety Pediatrics Regional Anesthesia Pharmacology