Intrathecal pain treatment for severe pain in patients with terminal cancer: A retrospective analysis of treatment-related complications and side effects

Linda Bengtsson; Sven-Egron Thörn; Lars-Erik Dyrehag; Olaf Gräbel; Paulin Andréll

doi:10.1515/sjpain-2024-0041

Artikel Open Access

Intrathecal pain treatment for severe pain in patients with terminal cancer: A retrospective analysis of treatment-related complications and side effects

Linda Bengtsson , Sven-Egron Thörn , Lars-Erik Dyrehag , Olaf Gräbel und Paulin Andréll

Veröffentlicht/Copyright: 4. Oktober 2024

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Aus der Zeitschrift Scandinavian Journal of Pain Band 24 Heft 1

Abstract

Objectives

Two-thirds of patients with advanced cancer experience pain. Some of these patients have severe pain refractory to oral and parenteral medication, for whom intrathecal pain treatment could be an option. While intrathecal therapy is presently used with good results in clinical practice, the current evidence is limited. Hence, increased knowledge of intrathecal pain treatment is needed. This retrospective study aimed to assess complications and side effects related to intrathecal pain treatment in patients with terminal cancer.

Methods

A retrospective study on all patients who received intrathecal treatment with morphine and bupivacaine through externalized catheters for cancer-related pain at a single university hospital during a 5-year period.

Results

Treatment-related complications were reported in 24 out of 53 patients. The most common complications were catheter dislocation (13%), catheter occlusion (9%), falls due to bupivacaine-related numbness or weakness (9%), and reversible respiratory depression (8%). There were five serious complications, i.e., meningitis or neurological impairment, of which four were reversible. Side effects related to intrathecal drugs, or the implantation procedure were observed in 35 patients. The most common were bupivacaine-related numbness or weakness (57%) and reversible post-dural puncture headache (19%). Systemic opioid doses decreased during the first 3 weeks of intrathecal treatment, from a median daily dose of 681 to 319 oral morphine milligram equivalents. The median treatment duration time was 62 days.

Conclusions

Complications related to intrathecal treatment are common, but mostly minor and reversible. Side effects are predominantly related to unwanted pharmacological effects from intrathecal drugs. Intrathecal treatment enables the reduction of systemic opioid doses, which indicates a good treatment effect on pain. Hence, intrathecal therapy can be considered a safe pain-relieving treatment in patients with severe refractory cancer-related pain. Future research is warranted on patient acceptability and satisfaction of intrathecal pain treatment.

Keywords: adverse effects; bupivacaine; cancer-related pain; drug side effect; opioid analgesics; spinal infusion

1 Introduction

Cancer is a leading cause of death globally and the prevalence is continuously growing. Worldwide, there were an estimated 19.3 million new cases and almost 10 million deaths due to cancer in 2020 [1]. Pain is experienced by two-thirds of patients with advanced, metastatic, or terminal cancer disease [2]. Most pain syndromes are mixed neuropathic and nociceptive [3]. According to WHO guidelines for the management of cancer pain, patients with moderate or severe pain related to cancer should be treated with an opioid, alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and/or paracetamol. Adjuvant analgesics such as steroids, antidepressants, and anticonvulsants have also been found to be beneficial. Opioids should be given orally or transdermally, and when this is not possible, the subcutaneous route is preferred [4]. The goal of pain management is to reduce pain levels to allow an acceptable health-related quality of life. The literature indicates that adequate pain relief can be achieved in 70–90% of patients when following guidelines for conventional pain management [2]. However, some patients have severe pain refractory to medication, and some also suffer from the negative effects of high doses of systemic opioids. For these patients, neuraxial administration of opioids, local anaesthetics, and alfa-adrenergic agonists could be an option [5].

Studies indicate that opioids in combination with local anaesthetics and/or alfa-adrenergic agonists provide better pain relief than opioids alone and that intrathecal administration is preferable over epidural administration [6–11]. Sjöberg and co-workers performed a prospective continuous trial on 53 patients with refractory cancer pain, reporting that all patients obtained acceptable pain relief with continuous intrathecal infusion of morphine and bupivacaine [12]. The infusion was administered by an externalized intrathecal catheter, a technique that has been described in detail by Nitescu et al. [13]. The use of these externalized tunnelled intrathecal catheters was not associated with higher rates of complications in this patient population when compared to internalized catheters connected to subcutaneously implanted pumps [14]. Later studies have likewise reported satisfactory pain relief with this regimen and found that serious complications are rare [15–17]. In a study by Bäckryd and Larsson, intrathecal therapy was more effective for spontaneous resting pain than movement-evoked pain [18]. In a systematic review, Kurita et al. found that existing evidence is of low quality and thus gave a weak recommendation for neuraxial administration of opioids with or without adjuvant analgesics in adult patients with cancer [19]. Recently, a systematic review and meta-analysis on intrathecal drug delivery systems for cancer pain found statistically and clinically significant differences in pain reduction. However, the authors concluded that the evidence is limited and that the results should be interpreted with caution [20]. The included studies have also been criticized regarding patient selection, data interpretation, and poor considerations of complications [21]. Hence, there is a need to assess the role of intrathecal therapy in managing severe cancer-related pain and increase the knowledge of its treatment effects on pain as well as treatment-related adverse events.

At Sahlgrenska University Hospital in Gothenburg, Sweden, patients with severe cancer-related pain refractory to conventional pain management with opioid and adjuvant analgesics, are offered intrathecal treatment with morphine in combination with bupivacaine. This treatment has been used at our hospital with clinically good results according to the same administration principles since the nineties. Previous studies have not included both complications and side effects [14,17], or have not categorized these as separate entities [16]. Thus, the aim of this retrospective study was to assess complications and side effects related to intrathecal pain treatment for severe pain in patients with terminal cancer. In addition, treatment effects on opioid consumption were evaluated.

2 Methods

2.1 Patients and setting

This was a retrospective study on all patients who received intrathecal treatment through externalized catheters for severe cancer-related pain refractory to conventional pain management at the Pain Centre, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden, during a 5-year period from January 2015 to December 2019. Patients implanted with externalized intrathecal catheters during the study period were identified through the hospital’s local surgical registry and those with a cancer pain treatment indication in medical records were included. Due to ethical considerations, patients still alive were excluded (Swedish Ethical Review Authority reg. no. 2021-02026).

2.2 Data collection

Through patient medical records, data were collected on age, gender, cancer diagnosis, pain characteristics, and treatment indication. Baseline data on pharmacological pain treatment before the initiation of intrathecal therapy were obtained as well as technical data regarding the catheter location and problems associated with catheter implantation. Data on treatment-related technical complications (i.e., dysfunction of the catheter or external pump) and biological complications (i.e., adverse effects on the patient) as well as treatment-related side effects were collected until treatment discontinuation. Generally predictable and expected unwanted effects from treatment were classified as side effects. Unexpected adverse effects were classified as complications. Consequently, expected negative pharmacologic effects from intrathecal treatment, as well as transient post-dural puncture headache after implantation or removal of the intrathecal catheter were classified as side effects. Respiratory depression is an expected pharmacologic effect on the first day after initiation of intrathecal treatment and the main reason patients are monitored in the recovery ward during the first night. However, as it is not expected later on and is a potentially life-threatening condition, respiratory depression was classified as a complication. Data regarding systemic opioid use were collected for the first 3 weeks of intrathecal therapy. Data on intrathecal pain medication were collected until discontinuation, i.e., permanent cessation of intrathecal treatment due to death or other reasons. Time from initiation of intrathecal therapy to discontinuation and reason for discontinuation were retrieved.

2.3 Outcome measures

Primary outcome variables were the type and frequency of complications and side effects related to intrathecal therapy. Secondary outcome variables were systemic opioid doses before and after initiation of intrathecal therapy, intrathecal therapy doses, and time to discontinuation and reason for discontinuation of intrathecal therapy. The day of catheter implantation and the start of intrathecal treatment was set to Day 0. The first 3 weeks of intrathecal treatment were divided into three periods: Days 1–7, Days 8–14, Days 15–21. Systemic opioid doses were converted to oral morphine milligram equivalents (MME) according to conversion factors presented in Table S1 [22–24]. The patients’ highest recorded daily doses in each period were used to calculate the median dose of systemic MME as well as the median doses of intrathecal morphine and bupivacaine. The median dose of systemic MME was calculated for the whole population and for quartile subgroups based on systemic MME before the initiation of intrathecal therapy. Only patients with complete dose data (documented dose of both continuous opioids and extra opioids as needed) were included in the analysis of systemic MME. There were no records of extra intrathecal bolus doses administered, hence the documented pump settings for maximum allowed extra dose per hour were used as a surrogate. Permanent cessation of treatment was classified as discontinuation regardless of the reason, including death.

2.4 Treatment

All patients received intrathecal treatment with morphine in combination with bupivacaine through an externalized intrathecal catheter. In five patients, clonidine was also added to the intrathecal solution. The intrathecal catheters were implanted under sterile conditions in the operating room by anaesthesiologists well-experienced in intrathecal pain treatment. A single dose of preoperative antibiotic prophylaxis was given. The spinal puncture level was chosen in relation to the pain location and anatomical considerations. The catheter tip was placed in proximity to the spinal region that innervates the painful area by approximation of distance. X-ray confirmation of catheter position was not routinely used. The catheter was tunnelled under the skin to the abdomen or the anterior chest where it was externalized and fixed with sutures and dressings. At the recovery ward, an external infusion pump was connected to the catheter and the intrathecal treatment was started. The intrathecal standard solution consisted of morphine 0.5 mg/mL combined with bupivacaine 2.5 mg/mL and the standard starting infusion rate was 0.1–0.2 mL per hour with access to patient-controlled boluses of 0.1 mL up to three times per hour. Ongoing systemic opioid treatment was routinely reduced to about half and the patients were instructed to preferably use the intrathecal bolus function when in pain. Secondarily, extra doses of systemic opioids were given as needed. The patients stayed at the recovery ward during the first night for observation and were discharged the next day to the hospital ward or home care. Treatment follow-up, including individual dose titration, was performed by nurses and physicians at the referral department in collaboration with the Pain Centre, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden.

2.5 Statistical analysis

Descriptive statistics were used, and analyses were performed in Microsoft^® Excel^® Version 2308. For categorical variables, n (%) was presented, and for continuous variables, the median (range min–max) was presented.

3 Results

3.1 Patient demographics and treatment indications

During the study period, 56 patients received intrathecal treatment through externalized catheters for severe cancer-related pain. However, three of these patients were alive at the time of study; these three patients were excluded due to ethical considerations. Subsequently, there were 53 patients in the study population. The patients came from the South-west region of Sweden; demographics are presented in Table 1. Intrathecal therapy was initiated due to insufficient pain relief from systemic pain medication in 45 (85%) patients and systemic pain medication in combination with epidural treatment in five (9%) patients. Intolerable side effects from systemic pain medication were documented as an additional reason in 18 of these patients. In three (6%) patients, pain relief was acceptable with epidural treatment in combination with systemic opioids, and the epidural infusion was converted to intrathecal therapy due to practical reasons. Catheter implantation details are presented in Table 2.

Table 1

Patient demographics

Number of patients (%)
Median age (range), years	57 (23–78)
Gender male/female	26/27 (49/51)
Cancer diagnosis
Colorectal	17 (32)
Upper gastrointestinal	10 (19)
Genitourinary	9 (17)
Gynecologic	8 (15)
Lung	4 (8)
Sarcoma	3 (6)
Breast	1 (2)
Head/neck	1 (2)
Pain location
Abdomen	30 (57)
Pelvis	29 (55)
Back	13 (25)
Chest	2 (4)
Lower limb	19 (36)
Upper limb	2 (4)
More than one site of pain	31 (58)
Pain type ^a
Nociceptive	15 (28)
Neuropathic	14 (26)
Mixed	24 (45)
Systemic pain medication before intrathecal treatment
Oxycodone	37 (70)
Fentanyl	28 (53)
Methadone	28 (53)
Hydromorphone	21 (40)
Morphine	12 (23)
Tapentadol	1 (2)
Paracetamol	35 (66)
Gabapentinoid	30 (57)
Antidepressant	26 (49)
Corticosteroid	26 (49)
NSAID	10 (19)
Epidural pain medication before intrathecal treatment
Ropivacaine	4 (8)
Standard solution^b	4 (8)

Data are number of patients (%), n = 53, otherwise specified.

^aClassified according to documented clinical assessments and pain descriptions.

^bBupivacaine 1 mg/mL, fentanyl 2 µg/mL and adrenaline 2 µg/mL.

Table 2

Catheter implantation details

Number of patients
Puncture level ^a and catheter length ^b
Th8/9	2
Th10/11	1
Th11/12	2
Th12/L1	6
L1/2	23
L2/3	12
L3/4	5
Median length in spinal cavity (range), cm	10 (7–19)
Reported implantation difficulties ^c
Any reported difficulty	27
Repeated attempts	22
Bloody tap	4
Paresthesia	5
Difficult tunnelling	2

Data are number of patients otherwise specified.

^aMissing data in two patients, n = 51.

^bMissing data in ten patients, n = 43.

^cMissing data in one patient, n = 52.

3.2 Treatment-related complications

There were documented complications related to intrathecal therapy in 24 (45%) patients (Table 3). Technical complications occurred in 13 (25%) patients among which catheter dislocation was the most common (13%). Most technical complications were resolved with minor bedside adjustments. In one patient, a new intrathecal catheter was implanted. In three more patients, re-implantation was needed to resume therapy, but this was not possible due to a deterioration in the medical condition and subsequent death. One technical complication required an unplanned change of intrathecal infusion solution, which was made by inexperienced staff, and resulted in an intrathecal drug overdose. There were 16 (30%) patients with biological complications of which five were serious such as meningitis or neurological impairment. Meningitis was documented in two patients, and both were successfully treated with antibiotics. In one of these patients, the intrathecal catheter was removed, and in the other, the catheter was left in place with 3 weeks of antibiotics and repeated consultations with physicians specialized in infectious diseases. Neurological impairment related to the intrathecal catheter or intrathecal drug administration was noted in three patients. In two of these patients, the impairment consisted of reversible nerve root pain. One patient with the catheter tip at the high thoracic level developed crossed brainstem syndrome [25] in close relation to the administration of an intrathecal bolus. The symptoms remained despite treatment discontinuation. Medical investigation with MRI displayed an 8 × 4 mm bleeding or cavernoma in the pons. There was a temporal relation between the intrathecal bolus administration and the onset of symptoms, but causality was not established. In total, four of the five serious complications were reversible. Respiratory depression occurred in four patients during observation at the recovery ward and in two of these patients on the next day at the hospital ward or home. Numbness or weakness related to side effects of intrathecal drugs precipitated falls in five patients. One of these patients had a fall that resulted in injury, consisting of a superficial head wound that required skin suturing. Other biological complications were intrathecal drug overdose (n = 1) and leakage of serous fluid from skin puncture sites (n = 2).

Table 3

Complications and side effects related to intrathecal treatment

Number of patients (%)
Complications
Any complication	24 (45)
Technical complication	13 (25)
Catheter dislocation	7 (13)
Catheter occlusion	5 (9)
Material breakage	3 (6)
Catheter system disconnection	2 (4)
Biological complication	16 (30)
Fall	5 (9)
Respiratory depression	4 (8)
Neurological impairment	3 (6)
Local infection	2 (4)
Meningitis	2 (4)
Other^a	3 (6)
Side effects
Any side effect	35 (66)
Post-dural puncture headache	10 (19)
Back pain related to implantation	2 (4)
Numbness or weakness	30 (57)
Lower limb	28 (53)
Upper limb	3 (6)
Face^b	2 (4)
Hypotension	4 (8)
Bladder function impairment	4 (8)
Cognitive impairment	4 (8)
Nausea	3 (6)
Other^c	4 (8)

Data are number of patients (%), n = 53.

^aIntrathecal drug overdose (n = 1), leakage of serous fluid from skin puncture sites (n = 2).

^bCatheter tip at the upper thoracic level.

^cTransient leakage of cerebrospinal fluid from skin puncture sites after implantation or removal of intrathecal catheter (n = 2), transient fecal incontinence (n = 1), opioid withdrawal symptoms after removal of intrathecal catheter (n = 1).

3.3 Treatment-related side effects

In 35 (66%) patients, there were documented side effects related to the pharmacological effects of intrathecal morphine and bupivacaine or the implantation procedure itself (Table 3). Numbness and/or weakness occurred in 30 patients, most commonly in the lower limbs (n = 28) and also the upper limbs (n = 3) and face (n = 2). Transient post-dural puncture headache after intrathecal catheter insertion (n = 9) or removal (n = 1) was observed in ten patients. Other infrequent side effects are presented in Table 3.

3.4 Systemic pain medication

Before initiation of intrathecal therapy, all patients were treated with one or more opioids and the median daily dose was 681 MME (range 30–4470, n = 41). Common additional pain medications were paracetamol, NSAIDs, corticosteroids, antidepressants, and gabapentinoids (Table 1). A few patients were treated with clonidine (n = 6), scopolamine butylbromide (n = 4), and ketamine (n = 3). During the first 3 weeks of intrathecal treatment, there was a substantial decrease in the median daily systemic opioid dose to 319 MME (range 0–1662, n = 26). For patients with complete systemic opioid dose data both before intrathecal treatment and during the first 3 weeks (n = 19), the median daily dose decreased from 854 (range 30–4470) to 180 (range 0–1662) MME (Figure 1). Analysis of these 19 patients in quartile subgroup based on opioid dose before intrathecal treatment confirmed a decrease in opioid dose in all four groups (range 40–90%) (Figure 2).

Figure 1

Median daily systemic opioid doses in oral MME (range min–max) for patients with complete systemic opioid dose data (i.e., documented dose of both continuous opioids and extra opioids as needed) in all periods (n = 19).

Figure 2

Median daily systemic opioid doses in oral MME for patients with complete systemic opioid dose data (i.e., documented dose of both continuous opioids and extra opioids as needed) in all periods (n = 19). Subgroups are based on systemic MME before initiation of intrathecal therapy. Subgroup 1 = 30–240 MME, Subgroup 2 = 241–854 MME, Subgroup 3 = 855-1463 MME and Subgroup 4 = 1464–4470 MME.

3.5 Intrathecal pain medication

The patients received intrathecal continuous infusion of morphine and bupivacaine with the possibility of extra bolus doses as needed. Median daily doses of continuous morphine and bupivacaine, as well as the maximum allowed extra bolus doses per hour, are presented in Table 4. The median starting doses of continuous morphine and bupivacaine were 1.2 (range 0.5–2.4) and 6.0 (range 6.0–12.0) mg per day, respectively. The median doses of continuous morphine and bupivacaine increased during the first 2 weeks and then stabilized (i.e., the highest doses were the same on Days 8–14 and Days 15–21) on 3.6 and 18.0 mg per day, respectively. The intrathecal median doses of continuous morphine and bupivacaine increased further throughout treatment up to 5.4 (range 0–67.2) and 24.0 (range 0–90.0) mg per day, respectively, at discontinuation (cessation or death). In five patients, intrathecal clonidine was added after Day 15. At discontinuation, the median continuous dose of clonidine was 96 µg per day and the median maximum allowed extra dose per hour was 12 µg.

Table 4

Intrathecal drugs during the first 3 weeks of treatment and at discontinuation

	Starting dose (n = 53)	Days 1–7 (n = 53)	Days 8–14 (n = 48)	Days 15–21 (n = 43)	Discontinuation ^a (n = 52)
Morphine
Continuous	1.2 (0.5–2.4)	2.4 (0.5–14.4)	3.6 (0.5–18.0)	3.6 (1.0–18.0)	5.4 (0–67.2)
Extra as needed	0.2 (0.1–0.8)	0.3 (0.1–1.8)	0.5 (0.1–2.3)	0.5 (0.1–2.3)	0.6 (0.1–8.4)
Bupivacaine
Continuous	6.0 (6.0–12.0)^b	12.0 (6.0–36.0)	18.0 (4.8–43.2)	18.0 (4.8–90.0)	24.0 (0–90.0)
Extra as needed	0.8 (0.8–1.5)	1.5 (0.8–4.5)	2.3 (0.6–6.0)	2.3 (0.5–11.3)	2.9 (0.2–11.3)

Median continuous daily dose mg per day (range) and median maximum allowed extra dose mg per hour (range). All patients received continuous infusion of morphine and bupivacaine with possibility of extra doses as needed. There was insufficient documentation of utilized extra doses in medical records and maximum allowed extra dose per hour according to pump settings are presented as surrogate. In five patients, intrathecal clonidine was added after Day 15. At discontinuation, the median continuous dose of clonidine was 96 µg per day and the median maximum allowed extra dose per hour was 12 µg.

^aDose at discontinuation was missing for one patient.

^bThe starting dose of continuous bupivacaine was 6.0 mg per day in 45 patients and 12.0 mg per day in 8 patients.

3.6 Treatment duration and reason for discontinuation

The median treatment duration was 62 days (range 5–376). Treatment was continued until death in 42 patients. In six patients, treatment was discontinued due to complications, i.e., catheter dislocation (n = 3), meningitis (n = 1), neurological impairment (n = 1), and serous fluid leakage from the catheter exit site (n = 1). In three patients, treatment cessation was possible following an improvement in the pain situation. Time to discontinuation and reason for discontinuation were missing in three and two patients, respectively, as there was no documentation in medical records.

4 Discussion

In this retrospective study on patients with severe pain from terminal cancer, both technical and biological intrathecal treatment-related complications were common but were mostly minor and reversible. Side effects were common and predominantly related to unwanted pharmacological effects from intrathecal bupivacaine. Intrathecal treatment enabled the reduction of systemic opioid doses indicating a good treatment effect. Most of the patients suffered from pain related to colorectal and upper gastrointestinal cancers. These diagnoses are indeed common causes of cancer-related deaths [26] and the results of this study are of relevance to these patient groups. There was an equal gender distribution and the pain experienced by patients was mostly mixed neuropathic and nociceptive as previously reported [3]. There were no complications during catheter implantations. Yet, despite the high experience level of implanting clinicians, difficulties were common. This indicates that catheter implantation is a complex procedure requiring experience and frequent training. In our hospital, an intrathecal catheter is mostly tunnelled to the anterior abdomen. At the exit site, the catheter is inserted into a plastic connector and fixated to the skin with sutures and dressings. Catheter dislocations occurred in 13% of patients which is lower than described by Kiehelä et al. (27%) [16], and comparable to rates seen in patients with implanted pumps [27]. Nitescu et al. [13] used an even more thorough external catheter fixation and tunnelling technique and reported catheter dislodgement or accidentally withdrawn catheter in only 5.5% of patients [14].

The total catheter infection rate was 8% (4 of 53 patients), which parallels the findings of Kiehelä et al. [16]. Studies on patients with implantable pumps have reported lower [17,28] and higher [27] infection rates. Two patients in our study suffered from meningitis and were successfully treated with antibiotics. Notably, the catheter was left in place in one of these patients with no recurrence of infection during the remaining treatment period of 9 months.

Numbness and weakness in the extremities are well-known dose-dependent side effects of intrathecal bupivacaine [12,29]. In our study, there was a rather high occurrence of numbness or weakness (57%), which precipitated falls in 9% of the patients. Kiehelä et al. [16] reported a lower rate of 32% (14 of 44 patients) even though the catheter implantation level was lower than in our study. One possible explanation could be that there were differences in bupivacaine doses between the studies. Indeed, the bupivacaine dose after titration seems to be higher in our study, with a stabilized median continuous bupivacaine dose of 18 mg per day compared to 10 mg per day. In contrast, the median continuous morphine doses are the same. The actual delivered intrathecal doses in our study are presumably even higher as all patients had access to extra doses. Kiehelä et al. more often added clonidine or ketamine to the intrathecal solution, which might have been a helpful way to keep the bupivacaine doses low according to Breivik [16,30]. In our study, the median intrathecal doses of continuous morphine and bupivacaine were further increased by 50 and 33%, respectively, from Week 3 to discontinuation. This probably reflects a dynamic pain situation due to the underlying progressive cancer disease. The discrepancy in the percentage increase of morphine and bupivacaine indicates that there were changes in intrathecal solution concentrations, most likely due to side effects from bupivacaine.

Systemic opioid doses were routinely reduced to about half when initiating intrathecal therapy, but the patients still had access to extra opioid doses as needed. Therefore, the decrease in systemic opioid doses likely reflects an actual reduced need, which is consistent with previous studies [16,18].

4.1 Study strengths and limitations

Sahlgrenska University Hospital has a long tradition of intrathecal therapy and well-established clinical routines. The study population size is comparable to or larger than those in recent studies on intrathecal pain treatment through externalized catheters [15,16,18]. However, the retrospective design confers limitations regarding data collection and interpretation. This is especially so when it comes to systemic opioid doses as there were missing data for many patients in home care or municipal care. In addition, there could be an underestimation of complications and side effects due to poor documentation in medical records, though we reason it is unlikely that serious adverse events have been left out.

4.2 Clinical implications

This study shows that intrathecal pain treatment with morphine and bupivacaine through externalized catheters provided by experienced clinicians is a safe pain-relieving modality in patients with terminal cancer. Intrathecal pain treatment enables a reduction of systemic opioid doses, indicating a good treatment effect consistent with clinical experience and previous studies [10,12,15,16]. It has been debated whether there is enough evidence to justify the use of neuraxial analgesics in the treatment of cancer-related pain, and current evidence is considered low quality due to the lack of large randomized controlled trials (RCTs), resulting in a weak recommendation [19]. Yet, intrathecal therapy is used with good results in clinical practice, and randomization to a potentially less effective comparator treatment in an RCT context is not seen as ethically acceptable [30,31]. Hence, when conventional pain medication has failed, we believe it is reasonable to offer intrathecal treatment as a possible option considering the overall assessment of clinical experience and the available evidence base, especially as there are few serious treatment-related complications. In our clinical experience, catheter insertion at the high lumbar level with a spinal catheter length of approximately 10 cm provides good conditions to achieve pain relief in the abdomen, pelvis, and lower limbs; these sites were the most common pain areas for patients included in our study. One should keep in mind that individual dose titration and close follow-up are needed throughout treatment and that pain control may have to be balanced against bupivacaine dose-related weakness and numbness in the lower extremities. According to Breivik, bupivacaine doses can be reduced by adding adjuvant drugs to the intrathecal solution [30], and therefore, adding clonidine might be beneficial in this regard. Thorough preoperative patient information, including complications and expected side effects, is crucial in clinical practice. Care providers should also be knowledgeable about the potential serious complications, such as meningitis, and that numbness/weakness in the lower extremities can lead to fall. Respiratory depression is uncommon, but when it does occur, prolonged observation in the recovery ward is recommended.

5 Conclusions

Technical and biological complications related to intrathecal treatment with morphine and bupivacaine through externalized catheters are common, but mostly minor and reversible. Side effects are predominantly related to unwanted pharmacological effects from the intrathecal drugs. Numbness and/or weakness in the lower extremities can potentially lead to fall. Intrathecal treatment enables the reduction of systemic opioid doses, which indicates a good treatment effect on pain. Hence, intrathecal therapy can be considered a pain-relieving treatment in patients with severe refractory cancer-related pain. Future research should focus on patient experiences about acceptability and satisfaction of intrathecal pain treatment. Systematic prospective follow-up studies of patient-reported outcomes and qualitative interviews with patients about treatment experiences are warranted to further assess the role and effectiveness of intrathecal pain therapy in terminal cancer.

Previous presentation: Abstract accepted for poster presentation at IASP 2024 World Congress on Pain, 5-9 August, Amsterdam, Netherlands.

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Research ethics: Research involving human subjects complied with all relevant national regulations, and institutional policies and is in accordance with the tenets of the Helsinki Declaration (as amended in 2013) and the study was reviewed by the Swedish Ethical Review Authority (reg. no. 2021-02026). The Ethical Review Authority had no ethical objections to the research study, but no formal review was performed since the study was not covered by the provisions of the Ethical Review Act.
Informed consent: Not applicable.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission. L.B., P.A., O.G., and L.E.D. designed the study. L.B. performed the data collection in consultation with P.A. All authors contributed to the analysis of the results. L.B. drafted the manuscript in consultation with P.A. and S.E.T. All authors were involved in revising and finalizing the manuscript. Furthermore, all authors approved the final version of the manuscript and agreed on the order of authorship.
Competing interests: The authors state no conflict of interest.
Research funding: This study was financed by Region Västra Götaland, Sahlgrenska University Hospital, Department of Anaesthesiology and Intensive Care Medicine/Pain Centre, Gothenburg, Sweden.
Data availability: The raw data can be obtained on request from the corresponding author.
Artificial intelligence/Machine learning tools: Not applicable.
Supplementary Material: This article contains supplementary material (followed by the link to the article online).

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Received: 2024-05-22

Revised: 2024-07-31

Accepted: 2024-08-09

Published Online: 2024-10-04

This work is licensed under the Creative Commons Attribution 4.0 International License.

Supplementary material

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https://doi.org/10.1515/sjpain-2024-0041

Schlagwörter für diesen Artikel

adverse effects; bupivacaine; cancer-related pain; drug side effect; opioid analgesics; spinal infusion

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BY 4.0

Intrathecal pain treatment for severe pain in patients with terminal cancer: A retrospective analysis of treatment-related complications and side effects

Artikel

Abstract

Objectives

Methods

Results

Conclusions

1 Introduction

2 Methods

2.1 Patients and setting

2.2 Data collection

2.3 Outcome measures

2.4 Treatment

2.5 Statistical analysis

3 Results

3.1 Patient demographics and treatment indications

3.2 Treatment-related complications

3.3 Treatment-related side effects

3.4 Systemic pain medication

3.5 Intrathecal pain medication

3.6 Treatment duration and reason for discontinuation

4 Discussion

4.1 Study strengths and limitations

4.2 Clinical implications

5 Conclusions

References

Zusatzmaterial

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