Treatment Efficacy of Neural Blockade in Specialized Palliative Care Services in Japan: A Multicenter Audit Survey

Introduction 

Pain is one of the most common complications in cancer patients, and it significantly impairs their quality of life. Empirical studies have demonstrated that more than 85% of cancer-related pain is pharmacologically controllable, but the remaining patients require a multidisciplinary approach.1, 2, 3, 4 As part of this multidisciplinary approach, many empirical studies have revealed the efficacy of neural blockade in cancer pain management refractory to standard pharmacological treatments.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 Audit assessment of interventional treatment is of importance to improve patients' quality of life by clarifying the types of patients likely to receive benefits. In Japan, however, no multicenter studies to date have investigated how frequently neural blockade is used in oncology or specialized palliative care settings; the efficacy and the predictors of successful interventions have not been evaluated. Therefore, as a preliminary study to develop a prospective audit registry system of neural blockade, we conducted this study with the primary aims: (1) to clarify the frequency of neural blockade in certified palliative care units and palliative care teams, (2) determine the efficacy of interventions, and (3) explore the predictors of successful or unsuccessful intervention.

Patients and Methods 

The study participants were consecutively recruited from the participating institutions. The inclusion criteria were adult cancer patients who required neural blockade to manage pain refractory to standard pharmacological management. The participating institutions were seven certified palliative care units and five hospital palliative care teams across the country, conveniently selected from 120 certified palliative care units and 20 palliative care teams where coresearchers were available. Due to the preliminary nature of this study and practical difficulties, we made no effort to enroll a representative sample of all specialized palliative care services in Japan. The institution researchers were requested to report all patients who received neural blockade for pain control in 2002–2003. For each patient, they reported pain intensity, performance status, communication levels, presence or absence of delirium, opioid consumption, and any adverse effects before and one week after the intervention on the basis of retrospective chart review. We used a structured data-collecting sheet and standardized rating protocols to maximize the reliability.

Results 

We obtained data on 162 interventions for 136 patients who required neural blockade during the study period. Eighteen patients received two procedures, and four patients received three procedures.

Table 1 shows the demographic characteristics of the patients. The main primary cancers were colorectal, gynecologic, and pancreatic.

Table 1. Patient Background (n=136)

		% (n)
	Mean age (years)	59±15
	Gender
	Male	63 (85)
	Female	37 (51)
	Performance status	2.7±1.0
	Mean survival (days)	103±105 (median 67)
	Treatment setting
	Palliative care units	43 (58)
	Palliative care teams	57 (78)
	Primary tumor site
	Colon, rectum	35 (47)
	Uterus, ovary	14 (19)
	Pancreas	13 (18)
	Prostate, kidney, bladder	8.1 (11)
	Lung	7.4 (10)
	Liver, gallbladder, bile duct	5.1 (7)
	Head and neck	3.7 (5)
	Stomach	2.9 (4)
	Breast	2.9 (4)
	Esophagus	2.2 (3)
	Soft tissue	2.2 (3)
	Blood	2.2 (3)
	Bone	1.4 (2)

Table 2 summarizes the procedures and pain characteristics. Common procedures were epidural nerve block with local anesthetics and/or opioids, neurolytic sympathetic plexus block, and intrathecal nerve block with phenol. Epidural block was temporary in 11 patients, and the median duration of placement was 22 days.

Table 2. Procedure and Pain Characteristics (n=162 Interventions)

		% (n)
	Procedures
	Epidural nerve block with local anesthetics and/or opioids	52 (84)
	Sympathetic plexus block	15 (24)
	Intrathecal nerve block with phenol	13 (21)
	Peripheral nerve block	6.8 (11)
	Epidural nerve block with phenol	5.6 (9)
	Intrathecal nerve block with local anesthetics	1.9 (3)
	Trigeminal nerve block	1.9 (3)
	Selective root block	1.9 (3)
	Impair ganglion block	1.2 (2)
	Stellate ganglion block	1.2 (2)
	Pain characteristics
	Location
	Hip, perineum, anus	30 (57)
	Lower extremity	18 (34)
	Abdomen	17 (32)
	Lumbar, back	14 (27)
	Chest	12 (22)
	Shoulder, upper extremity	5.3 (10)
	Head, neck	4.2 (8)
	Etiology
	Cancer-related	83 (135)
	Procedure-related	8.6 (14)
	Benign	8.0 (13)
	Characteristics
	Somatic	34 (55)
	Visceral	20 (33)
	Somatic and neuropathic	15 (24)
	Neuropathic	14 (22)
	Somatic and visceral	12 (19)
	Somatic and visceral and neuropathic	3.1 (5)
	Visceral and neuropathic	2.5 (4)

Treatment Efficacy and Safety 

Overall, pain intensity measured on the Support Team Assessment Schedule, performance status, and opioid consumption were significantly improved after neural blockade (Table 3). Opioid consumption fell 30% or more in 33% of the patients (n=43). In addition, there was a tendency toward improvement in the communication levels measured on the Communication Capacity Scale, although the difference did not reach significance.

Table 3. Overall Treatment Efficacy (n=162 Interventions)

		Before	One Week After	P
	Paina	2.9±0.8	1.7±0.9	<0.001
	Severe (≥3)	68% (n=110)	19% (n=31)
	Performance status	2.7±1.0	2.4±1.0	<0.001
	3 or 4	59% (n=96)	46% (n=74)
	Communication capacityb	0.31±0.67	0.26±0.62	0.083
	No clear communication	9.9% (n=16)	8.0% (n=13)
	Delirium	12% (n=19)	11% (n=18)	1.0
	Opioid consumption (mg/day)c	248±348	186±288	<0.001

a Evaluated using the Support Team Assessment Schedule over the range of 0-4. A higher score indicates a greater level of pain intensity. b Measured as Item 4 on the Communication Capacity Scale over the range of 0–3. A higher score indicates a greater level of communication impairment. No clear communication was defined as a score of 2 or 3. c Calculated as the total amount of oral morphine equivalent to a daily dose.

On the other hand, there was no significant improvement in the prevalence of delirium. In 19 patients with delirium, however, six patients (32%) recovered after interventions.

By subgroup analyses (i.e., epidural analgesia, neurolytic sympathetic plexus block, and intrathecal neurolytic analgesia), pain intensity was significantly improved after interventions in all subgroups (Table 4). There was no significant improvement in the communication level or prevalence of delirium. The performance status was significantly improved in the subgroups of patients receiving epidural analgesia and sympathetic plexus block, but not in those receiving intrathecal neurolytic analgesia. Opioid consumption significantly decreased in patients receiving epidural analgesia and intrathecal neurolytic analgesia, but not in those receiving sympathetic plexus block.

Table 4. Treatment Efficacy of Each Procedure

		Before	One Week After	P
	Epidural nerve block with local anesthetics and/or opioids
	Paina	3.0±0.9	1.7±0.9	<0.001
	Severe (≥3)	73% (n=58)	57% (n=45)
	Performance status	2.8±1.1	2.6±1.0	<0.001
	3 or 4	68% (n=54)	56% (n=44)
	Communication capacity b	0.2±0.5	0.2±0.5	0.32
	No clear communication	6.3% (n=5)	6.3% (n=5)
	Delirium	6.3% (n=5)	8.9% (n=7)	0.69
	Opioid consumption (mg/day)c	210±298	162±258	<0.001
	Sympathetic plexus block
	Paina	2.6±0.9	1.7±0.9	0.03
	Severe (≥3)	52% (n=12)	13% (n=3)
	Performance status	2.2±0.8	1.9±0.8	<0.01
	3 or 4	39% (n=9)	30% (n=7)
	Communication capacityb	0.1±0.5	0.04±0.2	0.16
	No clear communication	4.3% (n=1)	0% (n=0)
	Delirium	8.7% (n=2)	0% (n=0)	—
	Opioid consumption (mg/day)c	277±319	246±326	0.27
	Intrathecal nerve block with phenol
	Paina	2.7±0.7	1.5±0.9	<0.001
	Severe (≥3)	68% (n=13)	47% (n=9)
	Performance status	2.8±0.8	2.6±0.9	0.16
	3 or 4	68% (n=13)	47% (n=9)
	Communication capacityb	0.6±0.8	0.4±0.7	0.19
	No clear communication	21% (n=4)	11% (n=2)
	Delirium	26% (n=5)	16% (n=3)	0.50
	Opioid consumption (mg/day)c	452±588	295±419	0.014

a Evaluated using the Support Team Assessment Schedule over the range of 0–4. A higher score indicates a greater level of pain intensity. b Measured as item 4 on the Communication Capacity Scale over the range of 0–3. A higher score indicates a greater level of communication impairment. No clear communication was defined as a score of 2 or 3. c Calculated as the total amount of oral morphine equivalent to a daily dose.

Safety 

Adverse effects occurred in 15 of 162 procedures (9.2%) (Table 5). Detrusor sphincter dyssynergia occurred after intrathecal nerve block, although this was a predictable and informed complication in all cases. Other complications were transient, and no fatal event was reported.

Table 5. Adverse Effects

		n (%)
	Detrusor sphincter dyssynergia	5 (3.1)
	Hypotension	3 (1.9)
	Back pain	2 (1.2)
	Transitory motor weakness	1 (0.6)
	Infection	1 (0.6)
	Respiratory depression	1 (0.6)
	Headache	1 (0.6)
	Acute alcoholism	1 (0.6)

Predictors of Successful Treatment 

Pain intensity was significantly more improved in patients who survived 28 days or longer than others (Fig. 1, P=0.002). There were no significant differences in the changes in pain intensity between patients with a performance status ≤2 vs. those ≥3, and patients receiving more than 120mg oral equivalent of morphine per day vs. others (data not shown).

View Large Image Download to PowerPoint

Fig. 1 Changes in pain intensity between patients surviving 28 days or longer vs. less than 28 days.

Discussion 

This is the first multicenter study to assess the clinical utility of neural blockade in specialized palliative care services in Japan. One important finding is the clarification of the frequency of neural blockade in certified palliative care units and palliative care teams. In this study, 3.8% of patients receiving specialized palliative care services required neural blockade for acceptable pain control. This figure is generally close to the previous findings in Western countries,1, 2, 3, 4 and suggests that some cancer patients require interventional pain treatment to achieve maximum balanced analgesia. Specialized palliative care patients should thus have open access to pain specialists who can provide these interventions. Of special note was a significant, although modest, difference in the frequency of neural blockade among institutions: the treatment setting (palliative care units vs. teams) and the specialty of leading physicians. This indicates the strong need for explicit referral criteria for interventional pain treatment to maximize the appropriate referral of potentially benefiting patients.

The second and most important finding of this study is clarification of the efficacy and safety of these interventions. This study suggests that neural blockade can improve pain intensity, performance status, and opioid consumption without unpredictable serious adverse effects. This finding is consistent with previous studies,5, 6, 7, 8, 9, 10, 11 and strongly supports the clinical utility of neural blockade in carefully selected patient refractory to standard pharmacological pain management.

This study failed to demonstrate beneficial effects on communication levels and cognitive dysfunction such as delirium, despite an increased performance status and reduced opioid consumption. The possible interpretations are (1) lack of sensitivity of outcome measures, especially the retrospective nature of symptom assessment, (2) cognitive impairment occurring due to not only opioids but also deteriorated general conditions such as hypercalcemia and brain metastasis at an advanced stage, and (3) the small number of subjects resulting in a lack of sample power. In this study, however, six of 19 patients recovered from delirium, suggesting that neural blockade could improve cognitive impairment in some patients, such as those receiving high-dose opioids without other causes influencing cognitive capacity.

The third important finding is the exploration of predictors of successful or unsuccessful interventions. This study identified longer survival as an indicator of success in neural blockade. This result, along with a similar observation,6 suggests that earlier referral for neural blockade could contribute to a better quality of life of cancer patients.

This study is preliminary, and has several limitations. First, the retrospective nature of the assessment is an apparent limitation of the evaluation of treatment efficacy. Second, the participating institutions were selected for convenience, and so these findings cannot be automatically generalized to other institutions. Third, long-term efficacy was beyond our study aims. Fourth, no patients in this study received intrathecal opioid therapy, because this technique was not a common practice in Japan during this study period.

In conclusion, neural blockade was performed in 3.8% of cancer patients who received specialized palliative care in Japan. This could contribute to the improvement of pain intensity, performance status, and opioid consumption without unpredictable serious side effects. A prospective audit study is expected to identify the treatment efficacy of each interventional procedure in palliative care settings.