Persistent Use of Prescription Opioids Before and After Lumbar Spine Surgery: Observational Study With Prospectively Collected Data From Two Norwegian National Registries.

STUDY DESIGN: Prospective pharmacoepidemiologic study. OBJECTIVE: To investigate clinical and sociodemographic factors associated with persistent opioid use in the years following spine surgery among patients with persistent opioid use preceding lumbar spine surgery. SUMMARY OF BACKGROUND DATA: It is unknown whether successful spine surgery leads to a cessation of preoperative persistent opioid use. MATERIALS AND METHODS: Data from the Norwegian Registry for Spine Surgery and the Norwegian Prescription Database were linked for patients operated for degenerative lumbar spine disorders between 2007 and 2017. The primary outcome measure was persistent opioid use in the second year after surgery. Functional disability was measured with the Oswestry Disability Index (ODI). Factors associated with persistent opioid use in the year before, and two years following, surgery were identified using multivariable logistic regression analysis. The variables included in the analysis were selected based on their demonstrated role in prior studies. RESULTS: The prevalence of persistent opioid use was 8.7% in the year before surgery. Approximately two-thirds of patients also met the criteria for persistent opioid use the second year after surgery. Among patients who did not meet the criteria for persistent opioid use the year before surgery, 991 (3.3%) patients developed persistent opioid use in the second year following surgery. The strongest association was exhibited by high doses of benzodiazepines in the year preceding surgery (OR 1.7, 95% CI 1.26 to 2.19, P <0.001). Among patients without persistent opioid use, the most influential factor associated with new-onset persistent opioid use in the second year after surgery was the use of high doses of benzodiazepines (OR 1.8, 95% CI 1.26 to 2.44, P <0.001), high doses of z -hypnotics (OR 2.6, 95% CI 2.10 to 3.23, P <0.001) and previous surgery at the same lumbar level (OR 1.37, 95% CI 1.11 to 1.68, P =0.003). CONCLUSION: A substantial proportion of patients reported sustained opioid use after surgery. Patients with persistent opioid use before surgery should be supported to taper off opioid treatment. Special efforts appear to be required to taper off opioid use in patients using high doses of benzodiazepines. LEVEL OF EVIDENCE: 2; Prospective observational study.

"Do not resuscitate" order and end-of-life treatment in a cohort of deceased in a Norwegian University Hospital.

BACKGROUND: A "Do not resuscitate" (DNR) order implies that cardiopulmonary resuscitation will not be started. Absent or delayed DNR orders in advanced chronic disease may indicate suboptimal communication about disease stage, prognosis, and treatment goals. The study objective was to determine clinical practice and patient involvement regarding DNR and the prevalence of life-prolonging treatment in the last week of life. METHODS: A cross-sectional observational study was made of a cohort of 315 deceased from a large general hospital in Norway. Data on DNR and other treatment limitations, life-prolonging treatment in the last week of life, and cause of death were obtained from medical records. RESULTS: A DNR order was documented for 287 (91%) patients. Almost half the DNR orders, 142 (49%), were made during the last 7 days of life. The main causes of death were cancer (31%), infectious diseases (31%), and cardiovascular diseases (19%). The most frequent life-prolonging treatments during the last week of life were intravenous fluids in 221 patients (70%) and antibiotics in 198 (63%). During the last week of life, 103 (36%) patients received ICU treatment. Death by cancer (odds ratio 2.5, 95% confidence interval 1.24-5.65) and DNR decision made by a palliative care physician (odds ratio 3.4, 95% CI 1.21-3.88) were predictors of not receiving life-prolonging treatment. CONCLUSION: The findings of a high prevalence of life-prolonging treatment in the last week of life and DNR orders being made close to the time of death indicate that decisions about limiting life-prolonging treatment are often postponed until the patient's death is imminent.

Persistent Use of Prescription Opioids Following Lumbar Spine Surgery: Observational Study with Prospectively Collected Data From Two Norwegian Nationwide Registries.

STUDY DESIGN: Prospective pharmacoepidemiological study. OBJECTIVE: To investigate the use of prescription opioids 2 years following degenerative lumbar spine surgery. SUMMARY OF BACKGROUND DATA: There are limited data providing details to evaluate patterns of opioid use. The number of patients is often limited and data on opioid use following some of the most common surgical procedures are lacking. METHODS: Data from the Norwegian Registry for Spine Surgery and the Norwegian Prescription Database were linked on an individual level. The primary outcome measure was persistent opioid use the second year after surgery. Functional disabilitywas measured with the Oswestry disability index (ODI). Study participants were operated between 2007 and 2017. RESULTS: Among 32,886 study participants, 2754 (8.4%) met criteria for persistent opioid use the second year after surgery. Among persistent opioid users in the second year after surgery, 64% met the criteria for persistent opioid use the year preceding surgery. Persistent opioid use the year preceding surgery (odds ratio [OR] 31.10, 95% confidence interval [CI] 26.9-36.0, P  = 0.001), use of high doses of benzodiazepines (OR 1.62, 95% CI 1.30-2.04, P  = 0.001), and use of high doses of z-hypnotics (OR 1.90, 95% CI 1.58-2.22, P  = 0.001) the year before surgery were associated with increased risk of persistent opioid use the second year after surgery. A higher ODI score at 1 year was observed in persistent opioid users compared with non-persistent users (41.5 vs. 18.8 points) and there was a significant difference in ODI change (-13.7 points). Patients with persistent opioid use in the year preceding surgery were less likely to achieve a minimal clinically important ODI change at 1 year compared with non-persistent users (37.7% vs. 52.6%, P  = 0.001). CONCLUSION: Patients with or at risk of developing persistent opioid should be identified and provided counseling and support to taper off opioid treatment.Level of Evidence: 2.

Pain During Sex Before and After Surgery for Lumbar Disc Herniation: A Multicenter Observational Study.

STUDY DESIGN: Observational multicenter study. OBJECTIVE: The aim of this study was to evaluate changes in pain during sexual activity after surgery for lumbar disc herniation (LDH). SUMMARY OF BACKGROUND DATA: There are limited data available on sexual function in patients undergoing surgery for LDH. METHODS: Data were retrieved from the Norwegian Registry for Spine Surgery. The primary outcome was change in pain during sexual activity at one year, assessed by item number eight of the Oswestry disability index (ODI) questionnaire. Secondary outcome measures included ODI, EuroQol-5D (EQ-5D), and numeric rating scale (NRS) scores for back and leg pain. RESULTS: Among the 18,529 patients included, 12,103 (64.8%) completed 1-year follow-up. At baseline, 16,729 patients (90.3%) provided information about pain during sexual activity, whereas 11,130 (92.0%) among those with complete follow-up completed this item. Preoperatively 2586 of 16,729 patients (15.5%) reported that pain did not affect sexual activity and at 1 year, 7251 of 11,130 patients (65.1%) reported a normal sex-life without pain. Preoperatively, 2483 (14.8%) patients reported that pain prevented any sex-life, compared to 190 patients (1.7%) at 1 year. At baseline, 14,143 of 16,729 patients (84.5%) reported that sexual activity caused pain, and among these 7232 of 10,509 responders (68.8%) reported an improvement at 1 year. A multivariable regression analysis showed that having a life partner, college education, working until time of surgery, undergoing emergency surgery, and increasing ODI score were predictors of improvement in pain during sexual activity. Increasing age, tobacco smoking, increasing body mass index, comorbidity, back pain >12 months, previous spine surgery, surgery in two or more lumbar levels, and complications occurring within 3 months were negative predictors. CONCLUSION: This study clearly demonstrates that a large proportion of patients undergoing surgery for LDH experienced an improvement in pain during sexual activity at 1 year. LEVEL OF EVIDENCE: 2.

Clinical and ethical aspects of palliative sedation with propofol-A retrospective quantitative and qualitative study.

BACKGROUND: The anesthetic propofol is often mentioned as a drug that can be used in palliative sedation. The existing literature of how to use propofol in palliative sedation is scarce, with lack of information about how propofol could be initiated for palliative sedation, doses and treatment outcomes. AIM: To describe the patient population, previous and concomitant medication, and clinical outcome when propofol was used for palliative sedation. METHODS: A retrospective study with quantitative and qualitative data. All patients who during a 4.5-year period received propofol for palliative sedation at the Department of palliative medicine, Akershus University Hospital, Norway were included. RESULTS: Fourteen patients were included. In six patients the main indication for palliative sedation was pain, in seven dyspnoea and in one delirium. In eight of these cases propofol was chosen because of the pharmacokinetic properties (rapid effect), and in the remaining cases propofol was chosen because midazolam in spite of dose titration failed to provide sufficient symptom relief. In all patients sedation and adequate symptom control was achieved during manual dose titration. During the maintenance phase three of 14 patients had spontaneous awakenings. At death, propofol doses ranged from 60 to 340 mg/hour. CONCLUSIONS: Severe suffering at the end of life can be successfully treated with propofol for palliative sedation. This can be performed in palliative medicine wards, but skilled observation and dose titration throughout the period of palliative sedation is necessary. Successful initial sedation does not guarantee uninterrupted sedation until death. EDITORIAL COMMENT: In palliative care, some patients at the end of life can reach a stage where there have been maximal analgesic and or anxiolytic treatments though without achieving comfort in the awake state. This report describes and discusses use of propofol in these infrequent cases to relieve suffering as part of palliative care.

Defining the cut-off point of clinically significant postoperative fatigue in three common fatigue scales.

PURPOSE: Postoperative fatigue (POF) is an often underestimated problem after surgery. Studies on POF often report fatigue scores without relating this to the clinical relevance for the patients. The aim of this study was to define the cut-off point for clinically significant POF in three commonly applied fatigue scales; the Postoperative Fatigue Scale, Christensen's Fatigue Scale, and the Chalder Fatigue Questionnaire. The identification of cut-off points will make it possible to indicate whether statistically significant findings of increased fatigue are of clinical relevance. METHODS: We combined data from day 0 (pre-operatively) and day 1, 3, 6, and 30 after surgery in two fatigue-related studies with 442 patients. In order to define clinically significant fatigue, a key question was added in each questionnaire; "Given your current description of fatigue, would you say it has been of considerable significance to you?"; "Yes/No". We analysed each scale's ability to identify clinically significant fatigue, by performing receiver-operating characteristics (ROC) analyses, and calculated the optimal cut-off point between Sensitivity and Specificity. RESULTS: The average weighted cut-off point for clinically significant POF when measured with the Postoperative Fatigue Scale was ≥ 50 (scale range 0-100), with Christensen's Fatigue Scale ≥ 6 (scale range 1-10) and with the Chalder Fatigue Questionnaire ≥ 16 (scale range 0-33). CONCLUSION: In three commonly used fatigue scales, we have identified cut-off points for clinically significant fatigue among patients recovering from surgery. This can be particularly valuable for diagnostic purposes and in treatment evaluation. Further, it may be possible to analyse and review data from earlier studies in light of clinical relevance.

Opioids for outpatients with cancer in their last year of life: A nationwide pharmacoepidemiological study.

OBJECTIVE: Opioids are the main pharmacological treatment for moderate-to-severe cancer pain. Few longitudinal studies have examined the prescription prevalence (PP) of opioids to patients with cancer. The aims of the study were to examine 1) changes in the PP of opioids from 2005 to 2009 among outpatients with cancer who were in their last year of life and 2) associations between the PP of opioids and medical and sociodemographic factors. DESIGN: Retrospective, registry-based, national study. PATIENTS: This study used data on all patients with cancer who died 2005-2009, combining the following three complete nationwide registries; prescription data from the Norwegian Prescription Database, data on cancer diseases from the Cancer Registry of Norway, and sociodemographic data from Statistics Norway. RESULTS: The study population consisted of 44,579 adults (mean age 72 years at death, 54 percent males). The opioid PP increased from 74 to 82 percent during the study period. Oxycodone had the highest PP, and increased from 39.8 to 48.5 percent during the period, whereas the PP of morphine declined from 29.0 to 27.3 percent. The PP for fentanyl remained stable at 17 percent. The PP of opioids increased toward death with higher PP during the last 3 months of life compared to previous 3-month periods. Older patients (>60) were less likely to receive opioids, while prostate or pancreatic cancer increased the odds for opioid prescriptions (p < 0.001, Odds ratio [OR] 2.60 and OR 1.98, respectively). CONCLUSION: The PP increased yearly during the study period. Use of oxycodone increased while that of morphine decreased.

Persistent opioid use and socio-economic factors: a population-based study in Norway.

BACKGROUND: A growing proportion of the population is using opioids for longer time periods, but little is known about the characteristics of patients who are persistent opioid users. We therefore studied the association between socio-economic factors and persistent vs. short-term opioid use 4 years later. METHODS: The background population is the complete Norwegian population in 2001. The study population is derived from two groups aged 35 years or older in 2001 who met one of the following criteria in 2005: (1) persistent opioid users (n = 15,113) or (2) short-term opioid users (n = 214,061). The applied definition of persistent opioid use corresponds to an average daily dose indicating likely daily use of opioids during 365 consecutive days. The socio-economic factors work status, income, marital status, immigrant status and education were obtained from the Population and Housing Census of 2001, and data on opioid use in 2005 were obtained from the complete national Norwegian Prescription Database. For logistic regression analyses, the study population was stratified by gender and by age over/under 67 years. RESULTS: In the 35- to 67-year-old age group, receiving a disability pension was more common in persistent opioid users compared with short-term opioid users (48% vs. 16% for women, 36% vs. 9% for men). Adjusted odds ratios for receiving a disability pension were 6.51 and 5.77 for women and men, respectively. Being divorced/separated was associated with being a persistent opioid user (odds ratio of 1.4 for both genders). There were also negative associations between persistent opioid use and attained education level, an unemployed working status and income status. CONCLUSION: Disability pension, not working, divorce, low income and low education in 2001 were associated with persistent opioid use in 2005.

Early pharmacokinetics of nasal fentanyl: is there a significant arterio-venous difference?

OBJECTIVE: We have investigated the arterio-venous difference in the pharmacokinetics of 50 microg fentanyl during the first hour following nasal administration and documented its tolerability in opioid-naïve middle-aged to elderly patients. METHODS: Twelve male patients (range in age 47-84 years) scheduled for transurethral resection of the prostate gland received a 100-microl dose of 50 microg fentanyl base as a fentanyl citrate formulation in one nostril. Simultaneous arterial and venous blood samples for analyses of fentanyl were drawn at baseline and at 1, 3, 5, 7, 9, 13, 15, 20, 25, 35, 45 and 60 min after drug administration. Vital signs, sedation and symptoms of local irritation were recorded. RESULTS: The arterial C(max) (maximum serum concentration) of 0.83 ng/ml was nearly twofold higher than the venous C(max) of 0.47 ng/ml, and the arterial T(max) (time to maximum serum concentration) of 7.0 min was about 5 min shorter than the venous T(max) of 11.6 min. The arterial AUC(0-60) (area under the curve from 0 to 60 min after administration) of 21 min*ng/ml was approximately 30% larger than the venous AUC(0-60) of 15 min*ng/ml (all p values < or = 0.005). Venous T(max) and C(max) did not predict the corresponding arterial values. No significant adverse events were observed. CONCLUSION: A significant arterio-venous difference was present after intranasal administration of fentanyl. The short arterial T(max) complies with its rapid onset of action. The use of venous concentrations for the prediction of onset time of analgesia should be discouraged. A 50-microg dose of nasal fentanyl was well tolerated by opioid-naïve middle-aged to elderly male patients.