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Anesth Analg 2006;102:921-929
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000196687.88590.6b

REGIONAL ANESTHESIA

The Epidural Test Dose: A Review

Joanne Guay, MD, FRCPC

Department of Anesthesia, Maisonneuve-Rosemont Hospital, University of Montreal, Canada

Address correspondence and reprint requests to Dr. Joanne Guay, MD, FRCPC, Clinical Associate Professor, Anesthesia, Maisonneuve-Rosemont Hospital, 5415 L'Assomption Boulevard, Montreal, Quebec, Canada H1T 2M4. Address e-mail to joanne.guay{at}umontreal.ca.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
This review systematically examines the literature on the ability of the classical epidural test dose and other strategies to detect intravascular, intrathecal, or subdural epidural needle/catheter misplacement. For detection of simulated intravascular misplacements, a sensitivity (S) and a positive predictive value (PPV) ≥80 demonstrated by at least two randomized controlled trials coming from two different centers were determined for the following tests and patient populations: Nonpregnant adult patients = increase in systolic blood pressure (SBP) ≥15 mm Hg (S = 80–100 and 93–100; PPV = 80–100 and 83–100) or either an increase in SBP ≥15 mm Hg or an increase in heart rate ≥10 bpm after the injection of 10 (S = 100; PPV = 83–100) or 15 µg of epinephrine (S = 100; PPV = 83–100); pregnant patients = sedation, drowsiness, or dizziness within 5 min after the injection of 100 µg of fentanyl (S = 92–100; PPV = 91–95); and children = increase in SBP ≥15 mm Hg after the injection of 0.5 µg/kg of epinephrine (S = 81–100; PPV = 100). Conversely, more studies are required to determine the best strategies to detect intrathecal and subdural epidural needle/catheter misplacements in these three patient populations.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
The concept of first injecting a small dose of local anesthetic into the epidural space and then observing the patient for any signs of accidental intravascular or intrathecal injection was noted in the earliest texts on epidural anesthesia (1). Likewise, the term "test dose" was included in Dr Bromage's first textbook on epidural anesthesia (2). In 1981, Moore and Batra (3) proposed 45 mg of lidocaine with 15 µg of epinephrine as the ideal epidural test dose. The aim of an epidural test dose is to avoid the consequences of injecting a critical amount of local anesthetic or opioid either intravascularly, subdurally, or intrathecally. An ideal test dose should allow the detection of all needles/catheters misplaced in one of these three locations, should never gives a false-positive response that would lead to unnecessary catheter repositioning or manipulation, and should never induce serious side effects. The efficacy of the classic test dose in achieving this goal remains undetermined. Several case reports or case series have been published in which the test dose not only failed to identify the catheter misplacement but may even have induced a serious adverse event (4–6).

This review examines the ability of the classical test dose and other strategies to detect intravascular, intrathecal, or subdural epidural needle/catheter misplacement.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
The American National Library of Medicine's PUBMED was searched with the following keyword associations: "test dose AND epidural," "epidural AND ultrasound," "epidural AND noninvasive cardiac output monitoring," and "epidural AND Doppler." Reference lists of review articles obtained were checked for other possible relevant randomized controlled trials (RCT). For effectiveness (sensitivity [S] and positive predictive value [PPV]), only the highest level of evidence was kept: RCT > controlled clinical trial (CCT) > prospective cohort (observational) or case control study > retrospective study > case report. For RCTs and CCTs, the following data were extracted from texts or tables: number of patients included, number of tests administered, number of true- and false-positive tests, S, and PPV. Ss and PPVs obtained in experimental conditions (from the studies) were calculated when required. Each response to a definite dose of drug was considered as a separate test. For each test, data from a single study were pooled. When only one RCT or CCT was available, a 95% confidence interval (95% CI) for each S and PPV was calculated. Otherwise, Ss and PPVs are reported in percentages as range (from one study to another) for each test. From the known incidences of intravascular or intrathecal catheter misplacement in the clinical setup, and from the S and false-positive rates obtained in experimental conditions, posttest probabilities (PTP) and cumulative PTPs (independent tests only) were also calculated and are provided in percentages. Data were analyzed using the JMP 5.01 software (SAS Institute Inc., Cary, NC) and GraphPad StatMate (GraphPad Software Inc., San Diego CA).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The incidence of unintended intravascular entry by epidural catheters is estimated to be between 4.9% and 7% in the obstetrical population (epidural catheter inserted in parturient women for analgesia or Cesarean delivery) (7–9) with less intravascular entry undetected by aspiration of 2.3% for single-orifice and 0.6% for multiorifice catheters (1:63,000 for top-up doses) (7,8,10,11). In children, the incidence of accidental intravascular entry by epidural needle/catheter may be as frequent as 5.6% (12), and aspiration alone without previous injection fails to detect up to 86% of vascular entries (12).

The best results for S from nonpregnant adults were achieved with observation of an increase in heart rate (HR) ≥10 bpm or an increase in systolic blood pressure (SBP) ≥15 mm Hg with 10 or 15 µg of epinephrine equal to a decrease in T wave amplitude ≥25% after the injection of 10 or 15 µg of epinephrine (S = 100) greater than a decrease in T wave amplitude ≥25% after the injection of 5 µg of epinephrine (S = 95–100) greater than an increase in SBP ≥ 15 mm Hg after the injection of 15 µg of epinephrine (S = 93–100) greater than an increase in HR ≥ 10 bpm after the injection of 22.5 µg of epinephrine equal to an increase in SBP ≥ 15 mm Hg after the injection of 22.5 µg of epinephrine (95% CI for S = 83–100) greater than an increase in SBP ≥ 15 mm Hg after the injection of 10 µg of epinephrine (S = 80–100). Of the above, a PPV of 100 could be achieved for a decrease in T wave amplitude ≥25% after the injection of 5, 10, or 15 µg of epinephrine. A PPV ≥80 was noted for an increase in SBP ≥15 mm Hg with epinephrine 10 or 15 µg and for an increase in HR ≥10 bpm or in SBP ≥15 mm Hg with 10 or 15 µg of epinephrine. A 95% CI ≥80 for PPV was found for an increase in HR ≥10 bpm and for an increase in SBP ≥15 mm Hg with the injection of 22.5 µg of epinephrine. Therefore, a combined S and PPV of 100 could be achieved only with the observation of a decrease in T wave amplitude ≥25% after the injection of 10 or 15 µg of epinephrine (Table 1).


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  		Table 1. Identification of Intravascular Epidural Catheter Misplacement in Nonpregmant Adult Patients

 

Assuming an approximate rate of 3.3% of unrecognized accidental intravascular epidural catheter misplacement (28) using an increase in HR ≥10 bpm or in SBP ≥15 mm Hg with 10 or 15 µg of epinephrine would give a PTP of 14.6% for any of these two tests (10 or 15 µg of epinephrine).

The amplitude of an epinephrine response is attenuated by the following factors for HR: aging (18), previous administration of ß-adrenergic blocking drugs (selective or nonselective) (15), the combination of midazolam (arousable by verbal command) and fentanyl (2 µg/kg IV) (29), isoflurane (hemodynamic responses to intravascular injection of test doses vary with dose of epinephrine and depth of anesthesia) (30), sevoflurane (2% end-tidal concentration) (20), spinal blockade (31) or high (T5) thoracic epidural anesthesia combined with general anesthesia (32) but not by IV atropine (administered just before the test dose) (33), midazolam alone (29), oral clonidine (24), or low (T10) thoracic epidural anesthesia (32). The increase in SBP is affected by isoflurane (30), spinal (31) or high thoracic (T5) epidural anesthesia (32) but not by aging (18,34), ß-adrenergic blocking drugs (15), the combination of midazolam and fentanyl (29), oral clonidine (24), sevoflurane (20), or low (T10) thoracic epidural anesthesia (32). The T wave amplitude decrease is not affected by the combination of midazolam and fentanyl (29), sevoflurane anesthesia (21), or the electrocardiogram lead (I, II, III, or V (5)) monitored (35).

For pregnant women, the best results for S were achieved with fentanyl 100 µg (S = 92–100), Doppler precordium auscultation after the injection of 10 mL of agitated saline (95% CI for S = 89–100), an increase in HR >10 bpm after the injection of 10 or 15 µg of epinephrine (95% CI for S = 77 or 78–100), observation of both a metallic taste and tinnitus after the injection of 100 mg of lidocaine (95% CI for S = 79–100), and the injection of a combination of bupivacaine 12.5 mg + epinephrine 12.5 µg (95% CI for S = 75–100). Of the above, a PPV ≥80 was obtained for fentanyl 100 µg (PPV = 91–95), injection of 10 mL of agitated saline (95% CI for PPV = 89–100), and the combination of bupivacaine 12.5 mg + epinephrine 12.5 µg (95% CI for S = 82–100). Therefore, a combined S and PPV ≥80 could be achieved only for fentanyl 100 µg and the injection of 10 mL of agitated saline (Table 2).


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  		Table 2. Identification of Intravascular Epidural Catheter Misplacement in Pregnant Women

 

Assuming a prevalence of vascular catheterization unidentified by aspiration alone of 2.3% for single-orifice catheters (7,8) and of 0.6% for multiorifice catheters (8,10), the PTP of epinephrine, fentanyl, and agitated saline, respectively, would be 8.0%, 21.3%, and 16% for single-orifice catheters and 2.2%, 6.5%, and 4.7% for multiorifice catheters. A positive response to 2 independent tests would give a PTP of 50% (epinephrine + fentanyl), 41.4% (epinephrine + agitated saline), and 68.7% (fentanyl + agitated saline) for single-orifice catheters and 20.5%, 15.3%, and 36% for multiorifice catheters, respectively, for the same combinations. A positive response to the three tests would give a PTP of 89% and 67.5% for single- and multiorifice catheters, respectively.

For children, best Ss were obtained with an increase in HR ≥10 bpm after the injection of 0.75 µg/kg of epinephrine (95% CI for S = 84–100), an increase in T wave amplitude ≥25% with 0.25 µg/kg of epinephrine (95% CI for S = 83–100), an increase in SBP ≥ 15 mm Hg with 0.5 µg/kg of epinephrine (S = 81–100), an increase in SBP ≥ 15 mm Hg with 0.75 µg/kg of epinephrine (95% CI for S = 70–99), an increase in HR ≥ 10 bpm after the injection of 0. 5 µg/kg of epinephrine (S = 67–100), or an increase in HR ≥10 bpm after the injection of 0.25 µg/kg of epinephrine (95% CI for S = 62–97). Of the above, a PPV of 100 was noted for an increase in SBP ≥15 mm Hg with 0.5 µg/kg of epinephrine and for an increase in HR ≥ 10 bpm after the injection of 0.5 µg/kg of epinephrine, and a 95% CI ≥ 80 for PPV was found for the other variables. Therefore, a combined S and PPV ≥80 was present for an increase in SBP ≥15 mm Hg with 0.5 µg/kg of epinephrine only. A combined 95% CI ≥ 80 for both S and PPV was achieved for an increase in HR ≥10 bpm after the injection of 0.75 µg/kg of epinephrine and for an increase in T wave amplitude ≥25% with 0.25 µg/kg of epinephrine (Table 3).


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  		Table 3. Identification of Intravascular Epidural Catheter Misplacement in Children

 

Assuming an incidence of catheter/needle epidural entry undetected by aspiration of 4.8% (12), the PTP of an increase in SBP ≥15 mm Hg after the injection of 0.5 µg/kg of epinephrine would be 67.1% (for this value, the 95% CI of the false-positive rate was used).

IV atropine improved the epinephrine response in children anesthetized with halothane (HR) (58) or sevoflurane (SBP) (55). IV (59) or oral clonidine did not modify a test based on SBP (57). Leads I, II, III, or V (5) of the electrocardiogram are equally effective for the detection of T wave amplitude changes under sevoflurane anesthesia (60).

Some studies on the use of isoproterenol (nonpregnant adults, pregnant women, and children) or ephedrine (pregnant women) as a test dose for epidural catheter misplacement have been published. However, because the safety of injecting these substances in the epidural space has never been clearly established, these techniques will not be reported here.

In pregnant women, epidural catheter placement for labor analgesia or Cesarean delivery is associated with a 0.6%–1.6% frequency of dural puncture (8,61). However, a direct subarachnoid injection after a negative aspiration through the needle or the catheter is quite rare and has been estimated to be between 1 in 1750 (0.06%) and 1 in 126,000 (0.0008%) and can occur despite the use of a multiorifice catheter (10,61,62). In children, the incidence of accidental dural puncture associated with epidural techniques (caudal, lumbar, or thoracic) is reported to be 8 per 24,409 attempts (0.03%) (63).

No RCT demonstrating a combined S and PPV ≥80 were found for any of the substances evaluated to detect intrathecal catheter misplacement (lidocaine, bupivacaine, ropivacaine, or levobupivacaine). A CCT in pregnant women with 8 mg of bupivacaine achieved a combined 95% CI ≥ 80 for both S and PPV (83–100 for both values) (Table 4).


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  		Table 4. Identification of Intrathecal Epidural Catheter Misplacement in Adults

 

Even when assuming an approximate incidence as frequent as 0.6% of unintended subarachnoid block (28), the PTP is less than 6% for any of the following substances: lidocaine 45 mg and bupivacaine 15–20 mg (nonpregnant adult patients) or bupivacaine 8 mg (pregnant women).

There is actually no RCT or CCT evaluating the neurostimulation test (Tsui test) with one group of patients with a catheter within the intrathecal space and another with the catheter in the epidural space.

The incidence of catheter or needle subdural misplacement may be as frequent as 0.82% (69). It has clearly been demonstrated that a catheter cannot penetrate an intact dura mater (70). However, even when epidural blockade is performed by trained anesthesiologists, the needle may partly pierce the dura mater in up to 7% of the patients and create a potential passage for the catheter (71). A catheter may then enter the subdural space and either cannulate it or proceed through the subarachnoid membrane to penetrate the subarachnoid space (72). If the catheter is maintained within the subdural space, injection of the local anesthetic may produce a subdural block or tear the fragile subarachnoid membrane and produce a composite block or a spinal block. The latter could explain why it is possible to have a spinal block without any return of cerebrospinal fluid (CSF) through the catheter on first aspiration. For a subdural block, signs and symptoms will vary according to the catheter tip location. Because the subdural space has more capacity posteriorly and laterally where sensory fibers are located, a sensory block should be expected. However, a motor and sympathetic block will be present if the local anesthetic travels anteriorly. In Lubenow et al.'s (69) case series on 18 patients, symptoms were as follows: sensory levels much higher than expected from the dose of local anesthetic injected, no CSF aspirated, motor block in 10 of 18 patients, delayed onset more than 10 min in 11 patients (from 5 to 30 min), and hypotension ≥30% in 11 patients. Previous back surgery might be associated with an increase in the incidence of subdural block (69). The diagnosis can be confirmed by injecting a small volume of a contrast dye through the catheter and performing either a fluoroscopic or a computed tomography scan examination (73,74).

The classical test dose described by Moore and Batra (3)(lidocaine 45 mg with epinephrine 15 µg) may fail to reveal a subdural catheter misplacement (4). A recent case report described a woman in whom an intended epidural catheter was inadvertently placed 4 cm in the subdural space (needle at T10-11) without CSF return on catheter aspiration (diagnosis confirmed by computed tomography scan imaging) who had diffuse motor response (unilaterally at T3 and bilaterally at T10) with the neurostimulation test (0.8 mA) (74).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
There are no absolute criteria to evaluate the effectiveness of a diagnostic test. However, in general, a test with a S less than 80 would not be considered effective. When the consequences of having a false-positive test are significant, a high PPV also seems advantageous. Moreover, before recommending the systematic use of a diagnostic test, other issues including: (a) reproducibility (from one center to another), (b) effectiveness (as judged by its S and PPV, for instance), (c) complexity and cost, (d) consequences of misdiagnosis, (e) possible side effects of the test inflicted on the patients who did not have the disease (or problem) and are submitted to it must be weighed. Finally, the quality of the studies evaluating the above issues must be considered.

Defining the effectiveness of the various strategies proposed as an epidural test dose with the following criteria: both a S ≥80 and a PPV ≥80 demonstrated by at least 2 RCT coming from 2 different centers, few strategies would meet these criteria. There is reasonable evidence for intravascular misplacement detection in nonpregnant adult patients (observation of an increase in SBP ≥15 mm Hg or either an increase in SBP ≥15 mm Hg or an increase in HR ≥10 bpm after the injection of 10 or 15 µg of epinephrine), intravascular misplacement detection in pregnant women (signs of sedation, drowsiness, or dizziness within 5 minutes after the injection of 100 µg of fentanyl), and intravascular misplacement detection in children (increase in SBP ≥15 mm Hg after the injection of 0.5 µg/kg of epinephrine) (Tables 1–4). Because the injection of these doses of epinephrine in these two subpopulations (nonpregnant adult patients and children) have been extensively used without report of any serious side effects and the consequences of injecting large doses of local anesthetic intravascularly can be serious (75), a recommendation on their systematic use is reasonable.

When it comes to pregnant women however, the issue remains controversial. For the detection of intravascular catheter misplacement, the injection of epinephrine might be neither the best test (low PPV) nor have been sufficiently studied to be recommended, and significant side effects (decreased uteroplacental blood flow after IV or epidural injection) are possibly associated with its use (Table 2). Considering the infrequent incidence (0.6%) of undetected intravascular misplacement with the use of multiorifice catheters (8,10) and the small dose of local anesthetic administered to induce labor analgesia, some authors consider that the systematic injection of epinephrine in this situation is unjustified (36,37). They observe for failure to induce analgesia or sensory block after a small dose of local anesthetic, considering these cases possible undetected intravascular catheter misplacement. The risk benefit/ratio may differ when the epidural is performed for Cesarean delivery where the dose of local anesthetic is much larger and hence, consequences of a significant intravascular injection may be increased. Therefore, the routine addition of epinephrine in this situation may be reasonable and has been adopted by many anesthesiologists (76).

There is actually no RCT demonstrating that 45 mg of lidocaine would be more effective than any other strategy (including an alternate dose of lidocaine or injection of another local anesthetic) to detect intrathecal or subdural catheter misplacement or even demonstrating that lidocaine would be effective in detecting intrathecal or subdural catheter misplacement in any patient population. In addition, serious adverse events (total spinal block including respiratory paralysis, severe hypotension, and fetal bradycardia) have been associated with its use in pregnant women (5,6). Considering the extremely infrequent incidence of unrecognized intrathecal (0.53%) (28) or subdural (0.8%) (69) epidural catheter misplacement, a test with a PPV close to 100 in simulated situations is required to be clinically useful.

In conclusion, reasonable evidence can be found to recommend the systematic use of an epinephrine test dose in nonpregnant adult patients and in children for the detection of intravascular needle/catheter misplacement. For pregnant women, the epinephrine test dose might not be justified when a multiorifice catheter is inserted to induce labor analgesia. More studies are required to establish the best strategies to detect intrathecal and subdural catheter misplacement for all three patient populations.


   Footnotes
 
Accepted for publication October 19, 2005.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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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