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Why Do Pharmacologic Test Doses Fail to Identify the Unintended Intrathecal Catheter in Obstetrics?

Mhyre, Jill M. MD

doi: 10.1213/ANE.0b013e318273f625
Editorials: Editorials

From the Department of Anesthesiology, The University of Michigan Health System, Ann Arbor, Michigan.

Accepted for publication September 05, 2012

The author declares no conflicts of interest.

Reprints will not be available from the author.

Address correspondence to Jill M. Mhyre, MD, Department of Anesthesiology, The University of Michigan Health System, Room L3622 Women’s Hospital, 1500 E Medical Center Drive, Ann Arbor, MI 48105. Address e-mail to

High cephalad neuraxial block in the labor room is currently the most significant hazard of neuraxial labor analgesia according to closed claims analyses.1,2 The majority of reported events have developed within 30 minutes of the analgesic induction and have been attributed to unrecognized intrathecal catheters intended for the epidural space,1,2 despite the administration of a pharmacologic test dose that generally involved 45 to 80 mg of lidocaine.1 Why does pharmacologic testing fail to identify unintended intrathecal catheters in obstetric patients?

First, current pharmacologic tests for intrathecal placement rely on local anesthetics.3 Reviews of failed spinal anesthesia summarize the wide variety of mechanisms by which a spinal injection of local anesthetic might fail to achieve the expected effect; these include loss of injectate, anatomic barrier to uniform spread, pooling of hyperbaric solution below the lumbar curvature, ineffective drug, physiologic resistance, and large thecal volume.4,5 Each of these factors also contributes to the inconsistent sensitivity of the pharmacologic test dose to detect injection into the intrathecal space.

Second, intrathecal catheter placement undetected by gravity-dependent flow of cerebrospinal fluid or aspiration is rare, so any pharmacologic test must be performed with exceptional specificity to ensure that a positive test result actually indicates intrathecal catheter location. Dural puncture complicates approximately 1.5% of epidural catheter insertion attempts,6 but in the majority of cases, clear fluid drains from the epidural needle. Between 0.1% and 0.3% of the time, the epidural catheter is inserted into the intrathecal space;7–9 in this case too, gravity-dependent cerebrospinal fluid flow or aspiration detects the majority of intrathecal catheters. The residual risk of an unintentional intrathecal catheter after negative aspiration has been reported as 1 in 1750,10 1 in 7000,11 and 1 in 26,490 catheter insertions.12 Given this rarity, test specificity must exceed 95% for the positive predictive value to exceed 1%. False-positive tests result in the removal of appropriately sited epidural catheters, which delays analgesia and decreases efficiency. Moreover, a high false-positive test rate may create a clinical environment in which signs of intrathecal injection are missed or dismissed, leading to further local anesthetic administration, and high block.12,13

Third, little scientific attention has been devoted to evaluating the pharmacologic test for unintentional intrathecal placement of epidural catheters. Although a range of techniques have been developed to test for intravascular catheter location (e.g., epinephrine, local anesthetics, air, agitated saline, fentanyl), local anesthetics remain the cornerstone for the intrathecal pharmacologic test.3 Most evidence to define the testing characteristics for the intrathecal test dose in pregnant women is either extrapolated from nonpregnant populations,14,15 or derived from open clinical trials that compared the response of epidural doses administered to laboring women with the response of spinal doses administered to pregnant women undergoing cesarean delivery.16–18

In the current issue of Anesthesia & Analgesia, Pratt et al.19 report results from the first double-blind randomized controlled trial in pregnant women to compare the sensitivity and specificity of lidocaine 30 mg versus lidocaine 45 mg (each with epinephrine, but no dextrose) to distinguish the intrathecal space from the epidural space. The study was conducted in elective cesarean delivery patients using the combined spinal-epidural technique in which all women received both an intrathecal test dose and epidural saline placebo or the reverse.

The resulting sensory levels to both cold and pinprick were variable, with overlap between doses administered in the intrathecal and epidural spaces, regardless of the lidocaine dose. Furthermore, subjective symptoms of warmth or leg heaviness, reported 3 minutes after lidocaine injection, had insufficient specificity to be particularly helpful in diagnosing such a rare outcome for those with a positive result (specificity 74% [95% confidence interval {CI}, 55%–88%] with 30 mg and 59% [95% CI, 41%–74%] with 45 mg). Indeed, in clinical practice, early subjective signs of warmth or numbness indicate that the epidural catheter is located in the epidural or spinal space, as opposed to within a vein or out of the neuraxial space entirely.

Motor block appears to be more useful, but a full 5 minute delay may be necessary for accurate assessment. At the 3-minute measurement, lidocaine 30 mg produced less than 100% sensitivity (83% [95% CI, 65%–95%], while 45 mg produced less than 100% specificity (92% [95% CI, 76%–99%]). Based on an up–down sequential allocation design, Camorcia et al.20 reported that the ED50 value for lidocaine to produce a lower extremity motor block within 5 minutes is 13.7 mg (95% CI, 13.1–14.4), and extrapolated the ED95 to be 16.0 mg (95% CI, 14.1–17.9). A dose of 30 mg is approximately 2 times this estimated ED95, and should achieve a sensitivity that approaches 100%. In fact, all women in the current study who received intrathecal lidocaine 30 mg developed a motor block by 5 minutes.

The evaluation technique for motor blockade needs to be defined precisely, and likely depends on a woman’s baseline strength. Pratt et al.19 relied on the modified Bromage score, and identified a motor block in women who demonstrated detectable weakness of hip flexion while supine with full flexion of the knees. Baseline performance was not assessed, and 4 of 20 women were able to perform this task 3 minutes after receiving 30 mg of intrathecal lidocaine. In contrast, Camorcia et al.20 excluded women who were unable to perform the straight leg raise at baseline, and then documented a motor block if subsequent straight leg elevation attempts failed to clear 30 degrees. For nonpregnant individuals and for physically fit pregnant women, the straight leg raise may be the optimal test to detect early motor block. For the less physically fit, a modified test that allows for knee flexion may be more appropriate.

Common European practice is to forgo the pharmacologic test dose for intrathecal catheter location, and to consider the analgesic loading dose as a test dose.21,22 Straight leg raise has also been identified as the most discriminant finding after neuraxial administration of plain ropivacaine 15 mg and bupivacaine 10 mg;16,23 however, the onset of motor block with intrathecal administration can be relatively slow. Ropivacaine requires 8 minutes and bupivacaine 10 minutes to reliably exclude intrathecal placement, and to verify that the catheter is positioned correctly in the epidural space.16,23 At the same time, an epidural loading dose of 10 mL dextrose-free bupivacaine 0.1% can itself produce profound hypotension16 and even a high block24 if inadvertently administered in the intrathecal space.

Hyperbaric test solutions may offer better discrimination and margin of safety than plain local anesthetic solutions, which are all slightly hypobaric.25 Case reports describe high blocks that developed when plain lidocaine 45 mg and bupivacaine 8 to 10 mg were administered intrathecally in pregnant women.7,24,26 The authors of the current study hypothesized that lidocaine 30 mg might produce less extensive and profound anesthesia, with a lower risk of high block than lidocaine 45 mg; in fact, the study demonstrated no difference in the cephalad sensory levels between either group at any time point, and was insufficiently powered to determine the incidence of high block with either dose.19 Hyperbaric lidocaine 30 mg administered in the sitting position, may limit the risk of a high block while facilitating clear discrimination between epidural and intrathecal administration.18 Extrapolating from an observational study with hyperbaric bupivacaine, weakness in ankle plantar flexion may maximize sensitivity and specificity for an S1 motor blockade.17 High block remains possible if signs of intrathecal injection are not recognized, or if sufficient hyperbaric solution is administered.27

Catheter migration may complicate analgesic maintenance, and may lead to intrathecal drug administration and high block. Motor block may be an early discriminating sign of intrathecal migration,28 but motor block also complicates up to 50% of prolonged epidural infusions of dilute local anesthetic solutions.29,30 Consequently, regular assessment of the Bromage score (every 30 minutes) to identify progressive motor block density may be needed to raise suspicion for intrathecal catheter location. These frequent examinations require attention and expertise from nursing staff and can only be completed when the patient is awake.

Aspiration before every manual bolus31 and careful observation after the bolus32 are useful safety maneuvers that clinicians should use when administering a bolus through an epidural catheter. But widespread adoption of patient-controlled epidural analgesia renders these safety maneuvers largely impractical for routine analgesic maintenance. Moreover, current research is exploring the potential benefits of programmed intermittent epidural bolus administration.33 With programmed intermittent epidural bolus, the epidural infusion pump administers a preprogrammed bolus at a preset interval to a woman who may or may not be in pain, and who might even be asleep, without requiring that a clinician be present. Population-level surveillance is needed to determine whether this potential hazard will actually result in patient harm.

In the future, new technology may aid in the detection of intrathecal needle placement; recently reported strategies include nerve stimulation (e.g., the Tsui test),34–36 fiberoptic transmission of light combined with diffuse reflectance spectroscopy,37–39 acoustic signal guidance,40 bioimpedance analysis,39,41 and ultrasound-guided insertion.42,43 None of these techniques has focused on the epidural catheter tip location, and at present, no technique is sufficiently practical and accurate to replace the local anesthetic test dose.

The study by Pratt et al.19 not only reveals the limits of contemporary intrathecal testing with lidocaine but also suggests several testable scientific questions. Would motor block assessment 5 minutes after the injection of lidocaine 30 mg provide better discrimination than that at 3 minutes? Might hyperbaric lidocaine with assessment for a sacral motor blockade provide earlier discrimination than plain lidocaine? Is tailored motor block assessment necessary to optimize sensitivity for the physically fit, and specificity for the less fit? Ideally, future trials will be conducted in laboring women with painful contractions to define the accuracy of rapid analgesia to distinguish intrathecal from epidural catheter location. A number of details may be important, and should be clearly described, such as the volume of saline administered as part of the loss-of-resistance technique, epidural catheter design (e.g., single orifice versus multiorifice), patient positioning during the test dose administration and motor function testing, the exact language used to inquire about subjective symptoms, and the specific tests and timing to determine the presence of motor block.

Neuraxial labor analgesia is remarkably safe. Nevertheless, unrecognized intrathecal catheters continue to complicate epidural analgesia at a low but finite rate. Despite its imperfections, the epidural test dose prompts anesthesiologists to focus their attention on the early recognition of an intravascular or subarachnoid catheter.44 Careful attention to lower extremity strength testing both at the time the catheter is initially placed and tested, and throughout the course of the analgesic infusion, may improve recognition of the occasional intrathecal catheter.

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Name: Jill M. Mhyre, MD.

Contribution: This author conceived the idea, performed the literature review, and prepared the manuscript.

Attestation: Jill M. Mhyre attests to the accuracy of all statements contained herein.

This manuscript was handled by: Cynthia A. Wong, MD.

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