Inappropriateness of using opioids for end-stage palliative sedation: a Dutch study.

To be able to distinguish end-stage palliative sedation from euthanasia without having to refer to intentions that are difficult to verify, physicians must be able to manage palliative sedation appropriately (i.e., see that death is not hastened as a result of disproportionate medication). In the present study, we assessed whether or not this requirement is met in the Netherlands. We sent a retrospective questionnaire to 1,464 medical specialists, general practitioners, and nursing home physicians in the Netherlands. Furthermore, we held two sets of 20 and 22 semi-structured in-depth interviews with general practitioners, internists, lung specialists, and nursing home physicians. Although most guidelines discourage the administration of opioids alone for purposes of palliative sedation, opioids alone were administered for 22% of all the patients reported upon. Those physicians who were more experienced, general practitioners, and physicians who had consulted a palliative care expert administered only opioids significantly less often than the other physicians. The interviewees reported difficulties in assessing the appropriateness of medication, feeling uncertain about the pharmacokinetics of drugs used in moribund patients. Given that no more than 2% of the respondents perceived palliative sedation to be used as a form of euthanasia and that the use of opioids alone was not associated with shorter survival rates, the inappropriate use of opioids can only be attributed to a lack of knowledge or skill and/or a tradition of alleviating refractory dyspnoea with the use of opioids and not as an intentional means of hastening death.

Do diagnostic segmental nerve root blocks in chronic low back pain patients with radiation to the leg lack distinct sensory effects? A preliminary study.

BACKGROUND: The present preliminary study documents the effects of a selective nerve root block (SNB) with short or long acting local anaesthetic compared with baseline measurements in patients with chronic low back pain radiating to the leg with maximum pain in one dermatome (L4). METHODS: Ten consecutive patients underwent 20 controlled SNBs at L4 with ropivacaine 0.25% and lidocaine 1% in a prospective, randomized, double blind, crossover fashion. Baseline measurements included sensory function (assessed by pinprick on both unaffected and painful leg) and pain (Verbal Numeric Rating Scale; VNRS, 0-10). A change in size of areas with altered sensory function >10% and a VNRS change of 2 points were considered clinically significant. P-values<0.05 were considered statistically significant. RESULTS: Asymptomatic hypoaesthesia, variable in extent and non-dermatomal in distribution, was present in seven patients at baseline. It appeared to be more extensive and distal with longer duration of pre-existing pain. SNB produced no consistent changes in extent and distribution of hypoaesthetic areas. Change in VNRS did not correlate with the extent of pre-block or post-block hypoaesthesia. No differences in effects were found between lidocaine and ropivacaine. CONCLUSIONS: Pre-block assessment of sensory function is essential to assess the net effect of SNBs. In this small study group, SNBs failed to demonstrate uniform or distinct effects on sensory function.

[Parenteral administration of low dose ketamine for the treatment of neuropathic pain in cancer patients]. / Parenterale toediening van lage doseringen ketamine ter behandeling van neuropathische pijn bij patiënten met kanker.

In three patients, a 52-year-old woman with skeletal metastases from bladder carcinoma, a 54-year-old man with metastasised thyroid carcinoma and a 40-year-old man with a non-Hodgkin lymphoma, neuropathic pain developed that could not be alleviated adequately by patient-controlled opioid administration. It is known that ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, can improve opioid-induced analgesia. Pending invasive therapy, the three patients were given a continuous low dose of parenteral ketamine (2-5 micrograms/kg/min). The pain in the first two patients responded so well to ketamine that they decided to waive the invasive pain treatment and to continue the ketamine infusion at home until death. In the third patient, the addition of ketamine resulted in an adequate level of analgesia during the waiting period for invasive treatment with an intrathecal catheter.

[Providing regular relief; considerations for palliative care in the Netherlands]. / 'Verlichten: vaak'; aandacht voor palliatieve zorg in Nederland.

Over the last few decades the attention devoted to the palliative aspects of medicine, particularly those in hospital care, has declined due to the emphasis on medical technology. In Anglo-Saxon countries a review of this development resulted in structured palliative care that benefited terminally ill patients with a progressive fatal disease, especially cancer patients. Due to increasing national and international criticism of both the practice of euthanasia (assumed to be too liberal) and the lack of attention devoted to structured palliative care in the Netherlands, the Dutch government decided to improve the structure of palliative care. The government's viewpoint is based on the assumption that good palliative care that includes adequate pain control benefits patient care and might eventually lead to fewer requests for euthanasia. The improvements to palliative care should be realised by means of improvements in the structure, training and knowledge. Six academic medical clusters have been designated as Centres for the Development of Palliative Care (Dutch acronym: COPZ) for a 5-year period. Each COPZ must develop the various aspects needed to improve palliative care within the region it serves and ensure that its activities are carefully coordinated with those in the other centres. Research will focus on measuring the efficacy of palliative care as well as ethical and epidemiological aspects. A government committee will assess the appropriateness of the activities undertaken by each of the centres.

Inefficacy of high-dose transdermal fentanyl in a patient with neuropathic pain, a case report.

Pain partially responsive to opioids can lead to rapid escalating dosages due to tolerance development. In this report the case of a 58-year-old female with neuropathic pain using increasing transdermal (TTS) fentanyl dosages to a maximum dose of 3400 microg/h resulting in fentanyl plasma levels of 173 ng/ml is described. For pain relief an epidural infusion at the level T1-2 with bupivacaine was started. Immediate pain relief was accompanied by short lasting respiratory depression and drowsiness.

Diagnostic lumbosacral segmental nerve blocks with local anesthetics: a prospective double-blind study on the variability and interpretation of segmental effects.

BACKGROUND AND OBJECTIVES: Selective spinal nerve infiltration blocks are used diagnostically in patients with chronic low back pain radiating into the leg. Generally, a segmental nerve block is considered successful if the pain is reduced substantially. Hypesthesia and elicited paresthesias coinciding with the presumed segmental level are used as controls. The interpretation depends on a standard dermatomal map. However, it is not clear if this interpretation is reliable enough, because standard dermatomal maps do not show the overlap of neighboring dermatomes. The goal of the present study is to establish if dissimilarities exist between areas of hypesthesia, spontaneous pain reported by the patient, pain reduction by local anesthetics, and paresthesias elicited by sensory electrostimulation. A secondary goal is to determine to what extent the interpretation is improved when the overlaps of neighboring dermatomes are taken into account. METHODS: Patients suffering from chronic low back pain with pain radiating into the leg underwent lumbosacral segmental nerve root blocks at subsequent levels on separate days. Lidocaine (2%, 0.5 mL) mixed with radiopaque fluid (0.25 mL) was injected after verifying the target location using sensory and motor electrostimulation. Sensory changes (pinprick method), paresthesias (reported by the patient), and pain reduction (Numeric Rating Scale) were reported. Hypesthesia and paresthesias were registered in a standard dermatomal map and in an adapted map which included overlap of neighboring dermatomes. The relationships between spinal level of injection, extent of hypesthesia, location of paresthesias, and corresponding dermatome were assessed quantitatively. Comparison of the results between both dermatomal maps was done by paired t-tests. RESULTS: After inclusion, data were processed for 40 segmental nerve blocks (L2-S1) performed in 29 patients. Pain reduction was achieved in 43%. Hypesthetic areas showed a large variability in size and location, and also in comparison to paresthesias. Mean hypesthetic area amounted 2.7 +/- 1.4 (+/- SD: range, 0 to 6; standard map) and 3.6 +/- 1.8 (0 to 6; adapted map; P <.001) dermatomes. In these cases, hypesthesia in the corresponding dermatome was found in 80% (standard map) and 88% of the cases (adapted map, not significant). Paresthesias occurring in the corresponding dermatome were found in 80% (standard map) compared with 98% (adapted map, P <.001). In 85% (standard map) and 88% (adapted map), spontaneous pain was present in the dermatome corresponding to the level of local anesthetic injection. In 55% (standard map) versus 75% (adapted map, P <.005), a combination of spontaneous pain, hypesthesia, and paresthesias was found in the corresponding dermatome. CONCLUSIONS: Hypesthetic areas determined after lumbosacral segmental nerve blocks show a large variability in size and location compared with elicited paresthesias. Confirmation of an adequately performed segmental nerve block, determined by coexistence of hypesthesia, elicited paresthesias and pain in the presumed dermatome, is more reliable when the overlap of neighboring dermatomes is taken into account.

Substance P.

Substance P is considered to be an important neuropeptide in nociceptive processes. Although substance P was described more than 60 years ago, there is still controversy about its exact role in nociception. This article reviews the current knowledge about the function of substance P in pain. Special emphasis is put on how to use this knowledge in the development of new ways to treat pain.

Psychological predictors of the effectiveness of radiofrequency lesioning of the cervical spinal dorsal ganglion (RF-DRG).

In this study, 54 patients suffering from chronic cervicobrachialgia (mean pain duration 7 years) were treated with radiofrequency lesioning of the cervical spinal dorsal root ganglion (RF-DRG). The aim of the study was to investigate whether psychological variables would be predictive for the changes in pain intensity after medical treatment. The following psychological aspects were measured: pain cognitions, negative self-efficacy and catastrophizing, physical and psychosocial dysfunction, and overall distress. The level of catastrophizing before treatment appeared to predict 10% of the changes in pain intensity after treatment. Changes in pain intensity after RF-DRG were positively correlated with changes in psychosocial dysfunction and negative self-efficacy.

Elevated detection thresholds for mechanical stimuli in chronic pain patients: support for a central mechanism.

OBJECTIVE: To investigate the relation between pain provoking cervical segments identified by diagnostic dorsal root blockades and elevation of detection thresholds in patients suffering from chronic cervicobrachialgia (CCB). DESIGN: Quantitative sensory testing (light touch) of the cervical dermatomes using Semmes-Weinstein monofilaments. SETTING: A university pain clinic. SUBJECTS: Thirty-nine patients with CCB, with no clinical or diagnostic evidence of radiculopathy or surgically treatable bony lesion and with one main pain-provoking cervical segment identified by diagnostic dorsal root blockades. OUTCOME MEASURES: Detection thresholds with 95% confidence intervals (95% CI) of pain-provoking segments, compared with surrounding and contralateral segments and with normal values for cervical dermatomes. RESULTS: Patients' detection thresholds were significantly (p < .001) higher than those for normal subjects: 3.51 (95% CI, 2.71-4.31) and 3.10 (95% CI, 2.34-3.86), respectively. No significant differences existed between the segments. The elevations were systematic. However, thresholds on the painful side were consistently, slightly higher than those on the contralateral side. CONCLUSION: Supporting earlier studies, results from CCB patients in the present study showed systematic elevation of detection thresholds (low threshold mechanoreceptors), an adaptation in contrast with, but not contradictory to, central sensitization of high threshold neurons in chronic pain.

Intrathecal coadministration of bupivacaine diminishes morphine dose progression during long-term intrathecal infusion in cancer patients.

OBJECTIVE: To determine the difference in intrathecal morphine dose progression between a continuous intrathecal infusion of a morphine/bupivacaine mixture and morphine for pain relief in patients with cancer. DESIGN: Patients were treated with intrathecal drugs in a randomized study and followed prospectively until death. SETTING: Institute for Anesthesiology, Department of Pain Treatment, University Hospital Nijmegen, St Radboud, The Netherlands. PATIENTS: Twenty patients with cancer were selected for intrathecal treatment because of either side effects or inadequate relief during conventional pain treatment. INTERVENTIONS: Intrathecal drug infusion rates and medication were adjusted according to pain relief and side effects. OUTCOME MEASURES: Progression of intrathecal morphine dose during a phase of adequate analgesia in both groups following regression analysis and analysis of possible treatment related side effects. RESULTS: The combination of intrathecal morphine and bupivacaine resulted in a diminished progression of the intrathecal morphine dose (slope of regression line = 0.0003 vs. 0.005, p = 0.0001) during a phase of stable analgesia in comparison with the morphine group. No serious side effects presented. CONCLUSION: The diminished intrathecal morphine dose increase in the combination group is considered to be due to a synergistic effect of bupivacaine on the intrathecal morphine-induced antinociception. A dose increment during long-term intrathecal infusion in cancer patients appears to be related to both disease progression and tolerance phenomena.

Lumbar sympathectomy in critical limb ischaemia: surgical, chemical or not at all?

The value of surgical and chemical lumbar sympathectomy was studied in patients with critical lower-limb ischaemia without the option of vascular reconstruction. Clinical success rates, defined as improvement of ischaemia stage, and limb salvage rates were recorded for 76 limbs of 70 consecutive patients. Chemical lumbar sympathectomy patients were older and had more concomitant diseases than surgical lumbar sympathectomy patients. The short-term (6-week) success rate in 36 cases treated with surgical lumbar sympathectomy (44%) was better than in 40 cases treated with chemical lumbar sympathectomy (18%) (P = 0.01). The long-term (1-year) success rate was 47% for surgical lumbar sympathectomy and 45% for chemical lumbar sympathectomy (P = NS). The 1-year limb salvage rates were 61% for surgical lumbar sympathectomy and 58% for chemical lumbar sympathectomy (P = NS). Complications were minor in both groups. Lumbar sympathectomy still has a limited role in the treatment of critical limb ischaemia in patients without the option of vascular reconstruction. Both surgical and chemical lumbar sympathectomy can be performed with very little morbidity and may provide a benefit over the natural course of the arterial insufficiency.

Normal values for sensory thresholds in the cervical dermatomes: a critical note on the use of Semmes-Weinstein monofilaments.

In many healthy subjects, sensory thresholds for touch using Semmes-Weinstein monofilaments appear to be higher than the 2.83 filament, which some authors have suggested as a screening instrument. The currently proposed normal values, the interpretation of results, as well as the calibration of the filaments are questioned. A normative study of 20 normal subjects using Semmes-Weinstein monofilaments was undertaken at a pain clinic in a university hospital. The main outcome measures were sensory thresholds (touch) in dermatomes C3 to C8. Per subject, 24 sites were tested and 50 sites in dermatome C5 left of one subject. The threshold distribution patterns were analyzed. The mean threshold expressed in log (10 x F; with F = force in milligrams) of all sites (n = 480) in normal subjects was 3.10 (95% confidence interval, 2.34-3.86). The mean threshold per subject was 3.10 (range, 2.70-3.50). The mean threshold of 50 sites in dermatome C5 left of one healthy subject was 3.22 (range, 2.42-4.02). In the study contained herein, sensory thresholds in the cervical dermatomes have been shown to be higher than the generally proposed normal values. The cervical dermatomes show thresholds from 0.13 to 8.47 mN. This concurs with other authors. Results depend on the testing method, which in this study was different from previous studies. The testing method must be described accurately. The distribution of thresholds within all tested sites, dermatomes, subjects, or even within one dermatome in one subject are comparable. Individual results have to be related to the mean of the subject to determine abnormality. Calibration of the monofilaments is important. When these terms are met, testing with Semmes-Weinstein monofilaments is an easy, reliable, and relatively inexpensive method of quantitative sensory testing and can be a useful tool in the process of rehabilitation.

Pain characteristics help to predict the analgesic efficacy of radiotherapy for the treatment of cancer pain.

It is recognised that radiotherapy provides relief for intractable pain in approximately 50% of patients with cancer pain. Unfortunately, traditional explanatory variables, such as age, gender, histology or radiation dose, do not help to predict which individuals will benefit from palliative radiotherapy. A non-randomised prospective clinical trial was conducted on 51 patients to evaluate the value of pain characteristics as new explanatory variables for predicting the efficacy of palliative radiotherapy for providing cancer pain relief. Two new explanatory variables were identified: the presence of radiating pain and the pain score before radiotherapy.

Neurological impairment during long-term intrathecal infusion of bupivacaine in cancer patients: a sign of spinal cord compression.

Adequate pain relief in patients with far advanced cancer sometimes requires intrathecal (IT) administration of a combination of opioids and local anesthetics. Tumor progression as well as the IT administration of local anesthetics can lead to neurologic dysfunction during treatment. Five patients showed symptoms of compression of the cauda equina or spinal cord shortly after the start of combined IT administration of morphine and bupivacaine in a dosage usually not associated with neurologic symptoms. Unexpectedly, neurologic evaluation suggested compression of the cauda equina and spinal cord, which was confirmed radiographically. Manifestation of new neurologic symptoms during low dose bupivacaine infusion intrathecally might therefore be an early indicator of space-occupying processes within the spinal canal in cancer patients.

[Pain control in the terminal stage of life]. / Pijnbestrijding in de laatste levensfase.

A 67-year-old woman suffered from terminal cancer as a consequence of local recurrence of endometrial carcinoma which had been treated by hysterectomy. She had excruciating pains and was requesting euthanasia. Advanced techniques for pain relief e.g. intrathecal administration and nerve blocks resulted in adequate relief and postponed the request. Besides knowledge and skill, the application of these techniques requires a logistic network in the home situation. An alternative therapeutic approach for this patient would have been continuous intravenous administration of morphine, which would have implied accepting an earlier death. The Dutch National Inquiry on euthanasia and life ending interventions revealed that in 19.1 per cent of the overall mortality in the Netherlands, pain treatment had contributed to death. In 1.4 per cent (1900 cases per year) death was even the main goal of pain treatment. A wider application of advanced pain relieving techniques can diminish requests for euthanasia in the Netherlands and also can curtail mismanagement of pain. An advice from 1991 of the National Health Council for better hospital support for terminal patients in the home situation is still awaiting implementation.

[Intrathecal administration of morphine and bupivacaine in the treatment of severe pain in chronic pancreatitis]. / Intrathecale toediening van morfine en bupivacïne ter behandeling van ernstige pijn bij chronische pancreatitis.

A 25-year-old male with idiopathic chronic pancreatitis suffered from severe pain not reacting to medical therapy. Intractable pain persisted after the following procedures: subtotal resection of the pancreas, interpleural administration of bupivacaine, epidural administration of bupivacaine, and thoracoscopic sympathectomy. Eventually, adequate pain relief was achieved with intrathecal administration of morphine and bupivacaine. An infusion pump, externally controlled by radiotelemetry, was implanted subcutaneously for intrathecal drug administration. With this pump the patient was fully ambulant. Intrathecal administration of morphine and bupivacaine through an implanted pump is a possible new technique for pain management in chronic pancreatitis.