Epidural analgesia is widely used for management of labour pain because of its high level of efficacy; however, epidural catheter insertions still sometimes result in failed or inadequate blocks. Common techniques currently utilized to identify the correct placement of an epidural catheter include a test dose of local anesthetic, assessment of the clinical effect of the local anesthetic, and negative aspiration of blood and cerebrospinal fluid. Unfortunately, all of these methods have been shown to lack complete accuracy.1,2

The epidural electrical stimulation test (Tsui test) was first described utilizing epidural stimulation with a pulse width of 0.2 msec and a pulse frequency of 1 Hz, demonstrating a sensitivity of 100% and a specificity of 92% in a population of 40 non-obstetric patients.3 Results of another study by the same group in pregnant women receiving lumbar epidural analgesia showed 100% sensitivity and specificity.4 Overall, the positive predictive value of the Tsui test has been consistently high in the literature, with values ranging from 96-100%.3,4,5,6 Nevertheless, its negative predictive value has been shown to be inconsistent, with reported values in the literature ranging widely from 16-100%.3,4,5,6

Margarido et al. reported the specific characteristic of the motor response to the Tsui test in labouring women receiving lumbar epidural analgesia.7 In that study, the authors used a uniport wire-reinforced catheter, a pulse width of 0.2 msec, and a current of 0-20 mA, and they found that 91% of women exhibited a unilateral contraction in the lower limbs. Urmey et al. studied the effect of stimulation on peripheral nerves using differing pulse widths (0.1, 0.3, and 1.0 msec) and showed that increasing the pulse width allowed peripheral nerves to be stimulated with a lower threshold current at a farther distance from the source of the current.8 We anticipated that, because the Tsui test uses the same mechanism (pulsed electrical current) to stimulate spinal roots, the increase in pulse width would produce similar results, stimulating spinal roots that are further away from the source of the current. We assumed that such effect could potentially increase the incidence of bilateral motor response to the Tsui test, as opposed to the typical unilateral response, and perhaps it could be used to predict the symmetry/asymmetry of local anesthetic spread into the epidural space.

Tsui et al. also examined the effect of different pulse widths on eliciting motor responses during epidural placement.9 They examined the minimum current required to elicit a motor response in a porcine model, and their study results showed an inverse linear relationship between the pulse width and the minimum current required. Nevertheless, the response pattern to the stimulus (i.e., unilateral or bilateral) was not reported. We thus decided to study this phenomenon with the a priori hypothesis that the incidence of bilateral response to epidural stimulation would be greater with a 1.0-msec pulse width than with a 0.1-msec pulse width.

Methods

After obtaining Research Ethics Board approval from the Mount Sinai Hospital, Toronto, Canada (REB #16-00578-A; May 11th, 2016), we completed this randomized double-blind, crossover trial in women requesting labour epidural analgesia. The study was carried out from May to August 2016. Participants provided written informed consent prior to enrolment. We adhered to the CONSORT (Consolidated Standards of Reporting Trials) statement while reporting our findings.

The inclusion criteria were women aged 16-55 yr who requested labour epidural analgesia and were able to communicate in English. Exclusion criteria included refusal to provide written informed consent, abnormal vertebral anatomy (e.g., previous spine surgery or scoliosis); allergy or hypersensitivity to lidocaine, bupivacaine, or fentanyl; coexisting neurological disorders; and implanted electronic devices.

A resident, fellow, or staff performed epidural anesthesia in the typical manner at our institution. Spinal ultrasound was used to select the L2-L3 or L3-L4 interspace prior to performing epidural catheter insertion using an Arrow® FlexTip Plus® 19G multi-orifice wire-reinforced catheter (Arrow International Inc., Reading, PA, USA). The epidural catheter placement was performed using the midline approach with the patient in the sitting position. The epidural space was identified with the loss of resistance technique to either air or saline based on individual provider preference. Even though air and saline theoretically have different conductance, we chose not to standardize the loss of resistance technique but rather to facilitate successful placement of the epidural catheter by having each provider use the technique with which they were most comfortable. The epidural catheter was inserted 5 cm into the epidural space, aspirated to confirm the absence of blood or cerebrospinal fluid, and then secured in place.

The STIMPOD NMS450 nerve stimulator (Xavant Technology (PTY) Ltd; Pretoria, South Africa) was then connected to the epidural catheter through an Arrow-Johans ECG Adapter (Arrow International Inc., Reading, PA, USA). The epidural catheter and the adapter were primed with a standard volume of sterile normal saline 3 mL to allow for effective electrical conduction. We secured connections and prevented air from entering the system in order to avoid high impedance in the circuit. The cathode terminal of the stimulator was attached to the metal hub of the adapter, and the anode terminal was connected to an electrode placed over the deltoid muscle.

Epidural catheter stimulation was performed in all patients with both a 1-msec pulse width and a 0.1-msec pulse width. The order of the stimulus (0.1 msec vs 1 msec) was randomized using computer-generated blocks of ten. The patient and the individual assessing the motor response were blinded to the pulse widths. The current at each pulse width was increased from 0 mA until a motor response was observed or until the maximum current of 20 mA was reached. Following the control assessments, a test dose of 2% lidocaine 3 mL was administered and the epidural stimulation was then repeated five minutes later. The stimulus order was once again randomized and both the patient and the observer of the motor response were blinded.

An epidural loading dose of anesthetic solution consisting of 0.125% bupivacaine 10 mL and fentanyl 50 µg was then administered. Next, a programmed intermittent epidural bolus regimen was started with 0.0625% bupivacaine with fentanyl 2 µg·mL−1. The intermittent bolus dose was 10 mL every 40 min, and the first programmed bolus dose was given one hour after the loading dose. The patient was allowed to self-administer additional 5-mL bolus doses of the epidural solution with a lockout interval of ten minutes for a maximum total hourly volume of 30 mL. Bilateral sensory level to ice in the midclavicular line and lower extremity motor block (Bromage score 0-3, where 0 = no motor block; 1 = inability to raise extended leg, able to move knees and feet; 2 = inability to raise extended leg and move knee, able to move feet; and 3 = complete block of motor limb) were assessed 20 min after the loading dose. During the subsequent period, nurses were instructed to change the patient’s position every 30 min to minimize the effect of gravity on the distribution of the local anesthetic solution. A second test of sensory level and degree of motor block was conducted at two hours following the loading dose. The need for catheter replacement within two hours was noted.

The primary outcome was the motor response pattern to the epidural stimulation at baseline, either bilateral or unilateral. The secondary outcomes included sensory levels to ice in the midclavicular line at 20 min and two hours following the loading dose, rate of asymmetrical sensory blocks (defined as a difference greater than or equal to two dermatomal levels), magnitude of the electric current required to elicit a motor response at baseline and at five minutes after the test dose, degree of motor block on the lower limbs at 20 min and two hours following the loading dose, failure of epidural analgesia (defined as no evidence of a sensory block to ice with absent pain relief or the need for catheter replacement within two hours of the loading dose), consumption of local anesthetic in the first two hours, and the numeric rating score (from 0-10) for pain (where 0 = no pain and 10 = worst pain possible) measured before the test dose and at both 20 min and two hours after the loading dose.

Sample size calculation and statistical analysis

We based the calculation of the sample size required for our study on the following studies. Margarido et al. showed a unilateral motor response pattern to epidural catheter stimulation in 91% of patients while using a pulse width of 0.2 msec.7 In contrast, Charghi et al. showed a unilateral motor response rate of 52% while using a pulse width of 1 msec.5 In order to be conservative, we assumed an expected unilateral response rate of 70% in the 1-msec pulse width group compared with a 90% unilateral response rate in the 0.1-msec pulse width group. To achieve a power of 0.8 and a one-sided type 1 error of 0.05 with the above assumptions, the appropriate sample size was calculated to be 52 patients. The power and sample size analysis was completed with the exact conditional test for paired proportions, with a pair correlation of 0.1. Therefore, allowing for a 10% loss of patients, we planned a sample size of 60 patients for this study.

The mean (standard deviation [SD]) was reported for continuous normally distributed variables, and the difference between the groups was assessed using the paired Student’s t test. A P value < 0.05 was considered statistically significant. Median [interquartile range (IQR)] was reported for continuous non-normally distributed variables. To calculate the confidence interval (CI) for the difference in the rate of the primary outcome between the groups, we used the exact unconditional risk difference method. All statistical analyses were conducted with SAS® 9.3 (SAS Institute Inc., Cary, NC, USA).

Results

Thirty-eight women were approached to participate in the study and twenty were recruited. We initially planned to recruit 60 women into the study; however, after observing that the first 20 patients had the same motor response with either pulse width, we decided that the likelihood of a positive result was low if we continued to recruit 60 women. We did not complete a formal interim analysis or break the blind prior to the decision to conclude the study. Data from four patients were not available at two hours since delivery occurred prior to this point. In addition, data from one patient were excluded after the epidural stimulation at time zero because the catheter was determined to be intravascular and was removed after the test dose. Therefore, data were available from 20 patients at baseline, from 19 patients at five minutes after the test dose, and from 15 patients at two hours after the loading dose. The patient flow diagram is summarized in the Figure.

Figure
figure 1

Patient flow diagram

Full size image

Patient demographics, pain scores, sensory block levels, and degree of motor block are presented in Table 1. The rate of unilateral motor response in both the 0.1-msec (18/20) and the 1-msec (18/20) group was 90% (rate difference, 0%; 95% CI, −0.3 to 0.3; P = 1.0), while the other two parturients in each pulse width group had a bilateral motor response.

Table 1 Patient demographics, pain scores, sensory block levels, and motor block
Full size table

The current required to elicit a motor response with the Tsui test is shown in Table 2. The highest current required at time zero was 5 mA for the 1-msec group and 11 mA for the 0.1-msec group. In one patient with inadvertent intravascular epidural catheter placement, the stimulation was repeated at five, ten, and 15 min with no change in the baseline current of 5 mA at 1 msec and 11 mA at 0.1 msec. The epidural stimulation was performed with ease and with no discomfort in all enrolled patients.

Table 2 Characteristics of the Tsui test
Full size table

The mean (SD) total bupivacaine consumption within two hours after the loading dose was 13.7 (5.1) mg. Ninety-four percent of patients exhibited a symmetrical sensory block at 20 min, and 63% of patients exhibited a symmetrical block at two hours. No patients in the study required a nurse or physician to administer top-ups during the study period. The median [IQR] highest sensory block at 20 min was T9 [T7-T10] on the left and T10 [T7-T10] on the right. At two hours, the sensory block was T8 [T7-T9] on the left and T8 [T7-T9] on the right. All patients had a Bromage score of zero at both 20 min and two hours.

Discussion

This novel study compared the effects of different pulse widths on the response to the electrical stimulation of lumbar epidural catheters in humans. We showed that epidural catheter stimulation requires a much lower current for a 1-msec pulse width than for a 0.1-msec pulse width. Our study, however, did not show any change in the incidence of unilateral vs bilateral motor responses when the pulse width was increased from 0.1 msec to 1 msec.

In our practice, we have found the Tsui test to be clinically useful in several situations in the obstetric population. The Tsui test provides rapid determination of correct epidural catheter placement in morbidly obese women who typically have an epidural catheter placed early in labour for safety. Similarly, the Tsui test quickly identifies correctly placed epidural catheters in women with placenta percreta who have an epidural catheter placed but not activated prior to interventional radiology placement of prophylactic iliac artery balloons. Lastly, we also find the Tsui test useful when learners have achieved an equivocal loss of resistance, and it allows us to assess quickly whether the epidural catheter is in the epidural space. Although we do not use the test routinely, it has proven extremely useful in our practice in many specific situations.

The 90% unilateral motor response pattern observed with both the 0.1-msec and 1-msec pulse widths in this study is similar to previous studies in parturients undergoing lumbar epidural analgesia. For example, Margarido et al. observed a 91% unilateral motor response rate with a pulse width of 0.2 msec.7 Nevertheless, these rates of unilateral motor response are distinctly different from the observation of Charghi et al. with a much lower unilateral motor response rate of 52% in non-obstetric patients.5 Despite the unknown underlying mechanism, we postulate that the cause of this discrepancy may be due in part to electrical and anatomical reasons.

One possible explanation in the Charghi et al. 5 study is the use of a stimulating catheter with an exposed metal tip, while all other studies of the Tsui test used wire-reinforced epidural catheters. Although it is beyond the scope and objective of this study to examine and discuss the impact of this detail on the electrical properties of the catheter, it is important to point out that this concept has been previously examined. Patel et al.10 found no increase in the incidence of bilateral response when the stimulating and conducting surface area of the catheter was increased in an attempt to have more even spreading of the electric current (i.e., similar to a catheter with an exposed metal tip). This was achieved by utilizing a multi-orifice catheter instead of a single end-hole epidural catheter.

Another possible reason for the difference between these results may be due in part to the fact that Charghi et al. performed the stimulation in the thoracic epidural space, while Margarido et al. and our group in the current study performed the stimulation in the lumbar epidural space. Primary anatomical differences exist between the thoracic and lumbar spine, with the mean sagittal and frontal diameter of the normal subarachnoid space being smaller in the thoracic than in the lumbar levels.11,12 Thus, the physical distance between the left and right nerve roots at the thoracic level is also shorter than at the lumbar level and may have facilitated easier and more effective bilateral stimulation with the same current.

Finally, the lack of a difference in the motor response pattern with the varying pulse widths in this study may be due in part to the proximity of the 0.1-msec pulse width to the chronaxie of the motor fibres. Stimulation of motor fibres is more efficient when the pulse width is close to the chronaxie of the nerve. Chronaxie values of peripheral nerves of mammals have been shown to be 0.05-0.17 msec for motor nerves.13 Therefore, in spite of the 1-msec pulse width spreading farther than the 0.1-msec pulse width, the decreased efficiency of the longer pulse width may have resulted in no change to the rate of bilateral motor responses following the epidural catheter stimulation.

Asymmetric or one-sided effects of epidural catheters are a common reason for ineffective labour analgesia and failed conversion to surgical anesthesia. Our goal with this study was to show a higher rate of bilateral motor responses with the 1-msec pulse width and a possible association between bilateral motor response and symmetrical blocks. Unfortunately, since we observed high rates of unilateral motor responses with both pulse widths, we chose not to complete any further analyses of our secondary outcomes.

The ability of the 1-msec pulse width stimulation to elicit a motor response at lower currents could enable the test to be completed with most commercially available peripheral nerve stimulators. Most peripheral nerve stimulators used for locating peripheral nerves have a variable selection of pulse widths but deliver a maximum current of only 5 mA. In this study, 25% of catheters stimulated at the 0.1-msec pulse width had a motor response above a current of 5 mA. On the other hand, the rate of false negatives in our study was zero with a current limit of 5 mA for the 1-msec pulse width. The prospect of being able to complete epidural stimulation at a 1-msec pulse width with a readily available nerve stimulator and to maintain a low rate of false negatives is encouraging as it avoids the requirement for specialized nerve stimulators. Thus far, most studies published on the Tsui test have used specialized nerve stimulators to deliver currents of 1-10 mA at a 0.2-msec pulse width, as the motor response often occurs with currents > 5 mA.3 This may have been a contributing factor to the limited use of the Tsui test in clinical practice. The results of our study suggest that readily available peripheral nerve stimulators can be used if a pulse width of 1 msec is used, which could significantly improve the applicability of the test.

We initially planned to recruit 60 women into this study. Nevertheless, after observing that the first 20 patients presented the same motor response with either pulse width, it was obvious that the likelihood of a positive result was exceedingly low, even if we continued to recruit 60 women. Thus, it would be a futile and unnecessary continuation of a trial that was destined to conclude that the innovation of increasing pulse width is not superior to convert unilateral into bilateral motor response.14,15 Nevertheless, it can be argued that a limitation of this study is that we did not conduct a formal interim analysis or perform a futility stopping test14,15 prior to the decision to terminate the study.

In conclusion, our study did not show any difference in the motor response pattern following epidural catheter stimulation at different pulse widths. Both pulse widths, 0.1 msec and 1.0 msec, can be utilized when performing the Tsui test during lumbar epidural catheter placement in parturients. The prospect of using a 1.0-msec pulse width with most standard peripheral nerve stimulators at a maximum current of 5 mA is encouraging as it provides clinicians the option to utilize this valuable test without the need to acquire additional equipment. Nevertheless, a study with a larger sample size is required to prove this conclusion definitively.