The purpose of the present study was to evaluate if a procedure that confirms the site of herpes zoster infection using epidural electric stimulation is more effective in reducing pain and preventing PHN than a procedure that identifies the location using epidural catheters and contrast agents alone.
In the present study, pain scores of the patients in both groups were significantly lower over the 6 month follow-up period than the baseline pain scores. From 14 days to 6 months after the procedure (follow-up period), pain scores were significantly lower in the epistim group than in the esopocan group. The rate of complete remission of herpes zoster up to 6 months after the procedure was 1.9 times higher in the epistim group than in the esopocan group. This suggests that administering the drug after confirming the correct VZV-containing dorsal root ganglion using epidural electrical stimulation may be more effective in treating herpes zoster than the conventional continuous epidural block. The proportion of patients who received other epidural blocks because of the lack of pain control within the 6 months following the procedure was approximately one third lower in the epistim group than in the esopocan group.
There was also a difference in the drug injection site of the epidural catheter tip between the two groups. Reportedly, closed-tip, multi-orifice catheters are more effective for sensory blocks than open-tip, end-hole catheters; however, in the epistim group, where open-tip, end-hole catheters was used, a greater pain reduction was demonstrated than in the esopocan group, where closed-tip multi-orifice catheters were used [14, 15]. These results suggest that continuous epidural block, which uses electrical stimulation to confirm the location of herpes zoster, is more effective in achieving pain relief than the conventional continuous epidural block. EpiStim™ epidural catheters have a bent tip and a flexible guidewire as well as use electrical stimulation to identify the affected area, which increases the maneuverability of the catheter and makes it easier to position the catheter at the target site . These features yielded significant differences in our results between the esopocan and epistim groups.
In the present study, there was no significant difference in pain reduction immediately after the procedure between the two groups. This is likely due to the spread of the 8 mL of drug epidurally administered during the procedure. After administration, it is likely that the drug spread to adjacent dermatomes. Therefore, even if the epidural catheter was not precisely at the affected site, the drug may have still spread to the site of the herpes zoster infection; however, this would occur only with a single epidural block. When the drug was administered continuously at the rate of 4 mL/h via a portable infusion pump, the spread of the drug decreased considerably. Therefore, precise administration of the drug to the correct site would have been possible only if the catheter was positioned in close proximity to the site of herpes zoster infection. We determined that the reason for the difference in pain scores 14 days and 1, 3, and 6 months after the procedures was likely because if the catheter was correctly located in the target region, it would relieve pain despite the effects of the continuous administration of the drug having worn off.
Due to the complexity of the pathophysiological mechanisms that contribute to the progression of acute herpes zoster to PHN, various strategies have been proposed for its prevention, including vaccinations and use of antiviral agents, anticonvulsants, and corticosteroids; however, according to a recent systematic review and meta-analysis, the efficacy of these treatments in preventing PHN is limited [16-21]. For the treatment of acute herpes zoster and PHN prevention, we focused on the nerve damage caused by VZV. Reactivated VZV in the dorsal root ganglion, which manifests as herpes zoster, subsequently diffuses to the affected dermatome producing an inflammatory response and inducing nerve damage. Severe initial nerve damage or inability to regain normal function after the loss of nerve function can lead to PHN . Therefore, proactive treatment before nerve injury is induced can help prevent PHN. According to an additional recent meta-analysis, continuous epidural block in acute herpes zoster is effective in preventing PHN . The rationale behind applying epidural blockade to control acute herpes zoster pain and to prevent PHN is that the discontinued delivery of an invasive afferent stimulus to the central nervous system and improved flow of blood to the subjects’ nerve tissue will minimize neural damage and reduce sensitization. In addition, it is possible that local anesthetics, along with the anti-inflammatory effects of corticosteroids, could be important in areas corresponding to the affected nerves . Epidural administration of steroids not only inhibits inflammation but also reduces deafferentation by decreasing any neural ischemia resulting from inflammatory swelling . Local anesthetics administered epidurally control pain and interfere with sensitization by blocking sympathetic nerves; however, to maximize the effects of epidural steroids and local anesthetics on the affected site, it is important to administer the drug precisely to the site of nerve injury . We, therefore, performed epidural electrical stimulation to accurately identify the site sustaining the nerve injury caused by herpes zoster. This method allows for more accurate catheter placement than the conventional method, in which the diffusion image of a contrast agent is used to confirm the catheter’s location.
In the present study, the patients who could not maintain the inserted continuous epidural catheter for more than 10 days were excluded from the analysis because, according to a previous study, a single epidural block may be effective in controlling herpes zoster pain, but it has limited efficacy in the prevention of PHN [25, 26].
All the patients included in the present study underwent continuous epidural block and simultaneously took anticonvulsants and analgesics. To avoid bias due to drug treatments, patients who discontinued the drug due to side effects from other treatments, and patients who were administered drugs other than local anesthetics and steroids via the epidural catheter, such as opioids, were excluded from the analysis.
The complete remission rate in the present study was 51% in the esopocan group and 72% in the epistim group. Reportedly, the greater the severity of acute herpes zoster pain, the greater is the likelihood of its progression to PHN [5, 27]. In our clinic, invasive treatments, such as continuous epidural blocks, are not performed for less severe cases of herpes zoster (pain score, < 4). All the participants of the present study, therefore, had pain scores of 4 or higher (mean 7.5 ± 1.5, 7.1 ± 1.4), which could have been one of the reasons for the lower rates of complete remission. Additionally, the definition we adopted for complete remission (pain score of ≤ 2; no further medication prescribed) is possibly another reason, because other studies have defined a pain-free state with a NRS score of less than 3 or without mentioning withdrawal of medication [8, 25].
Epidural hematoma, infection, and abscess are the complications that make continuous epidural catheterization difficult; however, no epidural infections were reported after continuous epidural block in the present study. This is likely due to the involvement of well-trained physicians (who performed dressings daily) and well-educated patients and caregivers. The incidence of epidural hematoma is known to be low and was not observed in the present study; however, after the procedure, one patient experienced severe urinary retention, which was resolved after the epidural catheter was removed .
First, this was a retrospective study; therefore, there may be an influence of unmeasured confounding variables; however, to control for potential disturbance factors, we conducted a covariance analysis with the baseline demographics and underlying disease of the patients as covariates. Additionally, only the patients who took both anticonvulsants and analgesics along with continuous epidural block were included in this study to ensure consistent drug use across the sample.
Second, our research data were derived from electronic medical records, which may have led to an underestimation of the actual incidence of side effects. In the present study, continuous epidural block was stopped in only one patient because of adverse effects; however, side effects such as dysuria and motor weakness may not have been added to the medical record when the epidural block was maintained because of low symptom severity.
Third, we excluded patients who were treated with other interventional procedures within the 6 month period. This can cause a selection bias in this study; however, had we included patients who had received other interventions in the above analysis, there would have been uncertainty as to whether the patients’ symptoms improved because they received continuous epidural block for the first time or because they used other interventions. Therefore, we excluded patients who received other interventions when calculating complete remission and 6 month pain scores and analyzed the ratios separately.