[Principle of double effect and sedation for intractable distress: reflexion on survival in sedated patients]. / Théorie du double effet et sédation pour détresse en phase terminale : réflexion autour de la survie des patients sédatés.

The effect of sedation for intractable distress on survival in terminally ill patients is a debated question. For certain people, this would limit the physician's intervention to the detriment of symptom alleviation for patients. The principle of double effect is traditionally used to overcome this ethical conflict. Studies conducted between 1990 and 2009 fail to show that the death of patients undergoing sedation for intractable distress is hastened. Some authors conclude that sedation does not hasten death and claim that principle of double effect is unnecessary in this debate. In our view, caution is required in the interpretation of studies results and absence of evidence of sedation effects on survival cannot be considered as an evidence of absence of sedation effects on survival. Furthermore, we consider obtaining a definitive answer as impossible in the future, as the required cannot be conducted for ethical reasons. Caution, we think, is necessary, especially as sedation is sometimes used with explicit intention of hastening the end of life. Physician's intention, key point of the principle of double effect, comes back into the foreground of ethical debate on sedation for intractable distress. Far from limiting the physician's action, the principle of double effect, which requires us to clarify our intentions, should allow us to make the distinction between sedation for intractable distress and euthanasia.

Post-stroke pain on long-term follow-up: the Bergen stroke study.

The objective of this study is to evaluate characteristics and mortality related to long-term post-stroke pain (PSP). All surviving stroke patients admitted to the Stroke Unit, Haukeland University Hospital, between February 2006 and July 2009 received a postal questionnaire including the fatigue severity scale (FSS), the hospital anxiety and depression scale (HADSD), the Barthel index (BI), and questions regarding location of pain and pain severity at least 6 months after onset of stroke. Survival among patients returning the questionnaire was determined by November 2009. Stroke severity was defined by the modified Rankin score (mRS), 7 days after stroke onset. About 30% of the 408 patients had moderate to severe PSP. On logistic regression, PSP was associated with females (odds ratio (OR) = 2.1, p = 0.002), lower age (OR = 0.98, p = 0.04), fatigue (OR = 3.1, p < 0.001), sleep disturbances (OR = 3.3, p < 0.001), and mRS 3-5 (OR = 1.9, p = 0.03). Among patients with pareses (persistent or transient), there was no difference between paretic and non-paretic side as to frequency of limb pain on follow-up (p = 0.91). By November 2009, 26 patients had died. Cox regression analysis showed that mortality was associated with PSP (hazard ratio (HR) = 2.4, p = 0.040), high age (HR = 1.07, p = 0.001), males (HR = 2.5, p = 0.04), and low BI (HR = 0.97, p < 0.001). In conclusion, our study indicates a multifactorial basis for post-stroke pain. The main new findings were that the frequencies of pain were similar in paretic and non-paretic limbs and that long-term mortality was associated with post-stroke pain.

An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug-related toxicity, and possibly better survival compared with comprehensive medical management (CMM).

BACKGROUND: The randomized clinical trial of implantable drug delivery systems (IDDS) plus comprehensive medical management (CMM) versus CMM alone showed better clinical success at 4 weeks for IDDS patients. This 'as treated' analysis assessed if improvements in pain control, drug toxicity and survival were maintained over time. PATIENTS AND METHODS: We compared those who received IDDS with those who did not receive IDDS (non-IDDS). All patients had Visual Analogue Scores (VAS) for pain > or =5/10 on at least 200 mg morphine or equivalent daily. RESULTS: At 4 weeks, 46 of 52 (88.5%) IDDS patients achieved clinical success compared with 65 of 91 (71.4%; P=0.02) non-IDDS patients, and more often achieved > or =20% reduction in both pain VAS and toxicity [35 of 52 (67.3%) versus 33 of 91 patients (36.3%); P=0.0003]. By 12 weeks, 47 of 57 (82.5%) IDDS patients had clinical success compared with 35 of 45 (77.8%; P=0.55) non-IDDS patients, and more often had a > or =20% reduction in both pain VAS and toxicity [33 of 57 (57.9%) versus 15 of 45 patients (33.3%); P=0.01]. At 12 weeks the IDDS VAS pain scores decreased from 7.81 to 3.89 (47% reduction) compared with 7.21 to 4.53 for non-IDDS patients (42% reduction; P=0.23). The 12 week drug toxicity scores for IDDS patients decreased from 6.68 to 2.30 (66% reduction), and for non-IDDS patients from 6.73 to 4.13 (37% reduction; P=0.01). All individual drug toxicities improved with IDDS at both 4 and 12 weeks. At 6 months, only 32% of the group randomized to CMM and who did not cross over to IDDS were alive, compared with 52%-59% for patients in those groups who received IDDS. CONCLUSIONS: IDDS improved clinical success, reduced pain scores, relieved most toxicity of pain control drugs, and was associated with increased survival for the duration of this 6 month trial.

Use of sedation to relieve refractory symptoms in dying patients.

OBJECTIVES: To document the use of sedation for refractory symptoms in patients admitted to an independent palliative care unit. METHOD: A prospective descriptive study. SETTING: The 7-bed inpatient unit at Sungardens Hospice, Pretoria. SUBJECTS: Patients who required sedation for refractory symptoms in addition to normal palliative care treatment between January and June 2002. FINDINGS: Twenty of 100 consecutive patients admitted required sedation. All had advanced cancer. Their mean age was 68 years. Thirty-six per cent were men and 64% women. INDICATIONS: Agitated delirium was the most common reason (45%) for using sedation, followed by intractable vomiting due to inoperable malignant intestinal obstruction in 25% of patients. Three patients with persistent convulsions or myoclonic jerking and 2 patients with severe refractory dyspnoea required some sedation. Intractable pain was the main reason for sedation in only 1 patient. SURVIVAL: Mean survival following the start of sedation was 92 hours/3.8 days (range 6 - 369 hours/0.25 - 19.4 days). The combined mean survival recorded in 9 other studies was 57 hours/2.4 days (range 36 - 93.6 hours/1.5 - 3.9 days). MEDICATION: The main drugs used for sedation were midazolam and haloperidol. The mean dosage for midazolam was 18.5 mg/24 hours (range 7.5 - 40 mg) and for haloperidol 8 mg/24 hours (range 5 - 10 mg). For pain relief the mean daily dose of parenteral morphine was 76 mg (range 15 - 260 mg). CONCLUSION: Use of sedation for the relief of refractory symptoms at Sungardens Hospice is in line with several studies reported in the international literature.

Pain management, including intrathecal pumps.

Even when managed according to guidelines, approximately 14% of cancer patients have unrelieved pain or unacceptable side effects, and there is good evidence that patients still are not receiving optimal therapy. Implantable drug delivery systems (IDDS) administer small amounts of drugs directly to the spinal cord and reduce systemic narcotic exposure by a factor of 300 to one. In a large randomized trial of 202 patients with pain scores of 7.5 or higher, despite 200 mg or more of morphine or equivalent narcotics, IDDS gave better clinical success than comprehensive medical management (84.5% vs 70.8%, P=0.05). Pain scores were reduced by 52% versus 39%, drug toxicity scores were reduced by 50% versus 17%, and IDDS patients lived longer. Even the most refractory pain patients--those failed by a month of comprehensive medical management by experts--when subsequently provided with IDDS, had a 27% reduction in pain scores and a 50% reduction in drug side effects. Given multiple positive small cohort studies and a positive high-power randomized trial, IDDS should be considered as the best treatment for this population.

Analysis of the relationship between long-term operative success and a transient or delayed operative side effect.

OBJECTIVE: Investigators sometimes correlate the success of an operative procedure with the presence of an operative side effect that is thought to reflect the efficacy of the procedure in some way. When the prevalence of the side effect increases or decreases with time, this type of analysis can introduce a systematic bias. METHODS: Monte Carlo-simulated patient cohorts with independently and randomly generated operative success and presence of side effects were generated. Kaplan-Meier analyses of operative success were stratified by the presence of side effects at various times after the "operation." RESULTS: When the side effect (such as numbness after an ablative procedure) resolved during the study period in a significant proportion of patients, stratification by presence of the side effect at the end of the study period introduced a serious bias in favor of apparent better pain relief in patients without numbness. When the prevalence of the side effect increased with time (such as the requirement for a subsequent operation for radiation necrosis after brachytherapy or radiosurgical treatment of a glioma), the analysis was biased in favor of apparent longer survival for patients who experienced the side effect (i.e., those who required subsequent operations). CONCLUSION: Analyses of operative success stratified by the presence of postoperative side effects with time-varying prevalence may be seriously biased and should be interpreted with caution.

[Long-term intrathecal isobaric morphine therapy]. / Morphinothérapie isobare intrathécale au long cours.

In order to evaluate long-term intrathecal morphine therapy for cancer pain, whatever its location, 121 patients (80% were ambulatory patients) treated between April 1979 and April 1985 at the Cancer Institute of Montpellier (Centre Paul-Lamarque) were assessed. Morphine was stored in a presternal insulin syringe, protected by a sterile and waterproof dressing. A bolus administration of morphine via a subcutaneous lombo-epigastric subarachnoid catheter was scheduled every 12 h. This "closed" device was opened for refilling in an operating room only. The mean follow-up was 68 days (maximum: 13 months). More than 15,000 intrathecal injections were made. The mean daily amount of morphine required was 2.3 mg (extremes: 0.75 and 21 mg). All patients developed tolerance, requiring an adjustment of morphine dosages every 30 to 45 days. With the isobaric morphine solution, good or very good analgesia was achieved in 82% of patients, even in those suffering from thoracic or otolaryngologic pain. Mechanical complications (catheter coming out of the subarachnoid space in 7.67% of cases, leakage of CSF along the catheter in 9.16% of cases) were related to the exteriorization of the proximal catheter tip. With the exception of errors in manipulation, neither infection nor clinical respiratory depression were noticed. Nausea and vomiting were frequent but resolved spontaneously within a few days. Urine retention (33%) occurred mainly in men over 65 years, after pelvic surgery or radiotherapy. Because of the absence of a defined zone of analgesia, the small volumes required and the "ready for use" preparation, intrathecal isobaric morphine therapy will lead to easy self-administration via an implanted pump in the future.(ABSTRACT TRUNCATED AT 250 WORDS)