Use of peripherally inserted central venous catheters and midline catheters for palliative care in patients with cancer: a systematic review.

BACKGROUND: Peripherally inserted central catheters (PICCs) and midline catheters (MCs) may offer convenient intravenous access, but evidence to support their place in palliative care is limited. This review aimed to assess catheter indications, utilization, complications, dwell time, and patient experiences in cancer patients receiving palliative care. METHODS: A systematic search for studies on catheter utilization for supportive or symptom treatment was conducted in Medline, Embase, CINAHL, Web of Science, Cochrane, and CENTRAL databases. Studies with a study population or a subgroup of palliative care cancer patients were included. Study quality was assessed using the Effective Public Health Practice Quality assessment tool. RESULTS: Of 7631 unique titles, 17 articles were examined in detail, all published between 2002 and 2022. Median catheter dwell time varied from 15 to 194 days, the longest when utilized for home parenteral nutrition. For pain and symptom management, the typical duration was 2-4 weeks, often until the patient's death. Complication rates were minimal, with thrombosis, infections, and occlusion ranging from 0 to 2.46 incidents per 1000 catheter days. In studies from palliative care services, patients reported minimal distress during procedures and high user satisfaction. Quality of life assessments post-procedure improved, possibly influenced by concurrent specialist palliative care provision. All studies were assessed to be of moderate or weak quality. CONCLUSION: PICC and MC are safe and valuable tools in palliative care cancer patients who would benefit from intravenous access for symptom management. Further studies are needed to clarify indications for PICC or MC in palliative care.

"It turned out right for both of us": A qualitative study about a preference for home death and actual place of death.

This qualitative study was conducted in Norway to explore couples' preference for home death when one of the partners was dying from cancer, and what made home death possible or not. We conducted dyad interviews with five couples. After the patients' death, the spouses participated in individual interviews. The data were interpreted using thematic narrative analysis. One patient died at home, and three died in a healthcare institution. The narratives show how interdependency and mutual care were important when dealing with home death. When care needs were manageable at home, home was perceived a safe place and the preferred place for death. When care needs were experienced to become unmanageable at home, the sense of safety changed and admission to a health care institution was considered the best option. Regardless of place of death, the spouses experienced the end to have turned out right for their partner and themselves.

Prevalence of Triggers and Patient Harm Identified by Global Trigger Tool in Specialized Palliative Care.

Background: Global trigger tool (GTT) was developed for identification of patient harm. In palliative patients deterioration can be expected, and there are no data on whether cases classified as "patient harm" actually represents a potential for improved patient safety. Objectives: The primary aim was to test the performance and suitability of GTT in palliative care patients. The secondary aim was to pilot triggers for substandard palliative care. Design and Measurements: GTT was applied in 113 consecutive patients at a palliative ward at a Norwegian university hospital. Cases of patient harm were further evaluated to decide if the case was (a) a natural part of the disease trajectory or (b) a foreseeable consequence of treatment decisions. Potential triggers for substandard palliative care were tested. Results: Two hundred twelve triggers (1.9 per hospitalization) and 26 cases of patient harm were identified. The positive predictive value (PPV) for identifying patient harm was 0.12. The most prevalent harm was pressure ulcers (8.8%). Of the 26 cases of patient harm, 6 cases were a natural part of the disease trajectory and 10 consequences of treatment decisions. In 21 (18%) patients triggers being piloted for substandard palliative care were present, identifying 9 cases of substandard palliative care. The highest PPV (0.67) was observed for "Cessation of antibiotics less than 5 days before death." Conclusions: With the exception of pressure ulcers, GTT triggers were infrequent or had a very poor PPV for patient harm. Triggers related to overtreatment might be suitable for identifying substandard palliative care.

How should respiratory depression and loss of airway patency be handled during initiation of palliative sedation?

BACKGROUND: Loss of airway patency has been reported during initiation of palliative sedation. In present guidelines the loss of airway patency during initiation of palliative sedation is not addressed. Airway patency can be restored by jaw thrust/chin lift or placing the patient in the recovery position. AIM: A structured ethical analysis of how respiratory depression and loss of airway patency during initiation of palliative sedation should be handled. The essence of the dilemma is whether it is appropriate to apply simple non-invasive methods to restore airway patency in order to avoid the patient's immediate death. DESIGN: A structured analysis based on the four principles of healthcare ethics and stakeholders' interests. RESULTS: Beneficence and autonomy support a decision not to regain airway patency whereas non-maleficence lends weight to a decision to restore airway patency. Whether the proportionality criterion of the principle of double effect is met depends on the features of the individual case. The ethical problem appears to be a genuine dilemma where important values and arguments point to different conclusions. CONCLUSION: Whether to restore airway patency when the airway is obstructed during initiation of palliative sedation will ultimately be based on clinical judgment taking into account both any known patient preferences and relevant clinical information. There are strong arguments favoring both options in this clinical and ethical dilemma. The fact that a clear and universal recommendation cannot be made does not imply indifference regarding what is the clinically and ethically best option for each individual patient.

Use and safety of peripherally inserted central catheters and midline catheters in palliative care cancer patients: a retrospective review.

PURPOSE: Some cancer patients in palliative care require intravenous administration of symptom relieving drugs. Peripherally inserted central catheters (PICCs) and midline catheters (MCs) provide easy and accessible intravenous access. However, limited evidence supports the use of these devices in palliative care. The aim was to assess the use, safety, and efficacy of PICC and MC in this patient population. METHODS: A retrospective study of all palliative care cancer patients who received PICC or MC at the Department of Palliative Medicine at Akershus University Hospital between 2020 and 2022. RESULTS: A total of 374 patients were included; 239 patients received a PICC and 135 an MC with a total catheterization duration of 11,698 days. The catheters remained in place until death in 91% of patients, with a median catheter dwell time of 21 days for PICCs and 2 days for MCs. The complication rate was 3.3 per 1000 catheter days, with minor bleeding and accidental dislocation as the most common. The catheters were utilized primarily for opioids and other symptom directed treatments, and 89% of patients received a patient or nurse-controlled analgesia pump. Patients with PICC or MC discharged to home or nursing homes spent 81% of their time out of hospital. CONCLUSION: PICC and MC provide safe parenteral access for palliative care cancer patients where intravenous symptom treatment is indicated. Their use can facilitate intravenous symptom treatment beyond the confines of a hospital and supplement the traditional practice relying on subcutaneous administration.

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.

Ought the level of sedation to be reduced during deep palliative sedation? A clinical and ethical analysis.

BACKGROUND: Deep palliative sedation (DPS) is applied as a response to refractory suffering at the end of life when symptoms cannot be relieved in an awake state. DPS entails a dilemma of whether to provide uninterrupted sedation-in which case DPS would turn into deep and continuous palliative sedation (DCPS) -to minimise the risk that any further intolerable suffering will occur or whether to pause sedation to avoid unnecessary sedation. DPS is problematic in that it leaves the patient 'socially dead' by eradicating their autonomy and conscious experiences. AIM: To perform a normative ethical analysis of whether guidelines should recommend attempting to elevate consciousness during DPS. DESIGN: A structured analysis based on the four principles of healthcare ethics and consideration of stakeholders' interests. RESULTS: When DPS is initiated it reflects that symptom relief is valued above the patient's ability to exercise autonomy and experience social interaction. However, if a decrease in symptom burden occurs, waking could be performed without patients experiencing suffering. Such pausing of deep sedation would satisfy the principles of autonomy and beneficence. Certain patients require substantial dose increases to maintain sedation. Waking such patients risks causing distressing symptoms. This does not happen if deep sedation is kept uninterrupted. Thus, the principle of non-maleficence points towards not pausing sedation. The authors' clinical ethics analysis demonstrates why other stakeholders' interests do not appear to override arguments in favour of providing uninterrupted sedation. CONCLUSION: Stopping or pausing DPS should always be considered, but should not be routinely attempted.

Filled prescriptions for opioids among children and adolescents - A nationwide study from 2010 to 2018.

BACKGROUND: Prescribing opioids for children and adolescents should be reserved for advanced life-limiting diseases and moderate-to-severe acute pain. Pediatric codeine use is discouraged by several authorities, but the effects of these recommendations are not fully known. We investigated opioid utilization trends among 0-18-year-olds and characterized those who filled ≥1 opioid prescriptions, with emphasis on those who did so >3 times within a year. METHODS: The prevalence of filled opioid prescriptions among 0-18-year-old Norwegians in 2010-2018 (N = 77,942) was measured from nationwide healthcare registries. Characteristics, healthcare utilization, and other drug use of those who newly filled 1, 2-3, or >3 opioid prescriptions in 2011-2014 were compared to 2015-2018, excluding persons with cancer. RESULTS: From 2010 to 2018, the prevalence of opioid use decreased from 9.0 to 7.0 per 1000 persons. The largest decrease was among children <12 years, from 4.1 to 0.4 per 1000 persons, mainly due to decreasing codeine use. The proportion of those who filled >3 opioid prescriptions was 2.1% in 2011-2014 and 3.1% in 2015-2018. Those with >3 dispensations had a median of 4 contacts/year with secondary healthcare (interquartile range 2-7); the most frequent diagnoses indicated post-surgery follow-up. Most commonly dispensed other drugs were non-steroidal anti-inflammatory drugs. CONCLUSIONS: Opioid dispensations for the young have declined in recent years. Multiple opioid dispensations were rare and associated with frequent healthcare utilization. Reducing codeine is in line with recommendations, but the effects of decreased opioid use on the quality of pain management remain unknown.

Prescriptions of analgesics during chronic cancer disease trajectories: A complete national cohort study.

PURPOSE: Pain management principles vary considerably between chronic noncancer, acute and cancer pain. Cancer patients responding to oncological treatment may live with low tumor burden for years. Opioid treatment should reflect that the ratio between benefits and risks in these patients is different from patients with a rapidly progressive disease. Our study investigated the prescription patterns of analgesics in patients who died 6 to 9 years after cancer diagnosis. PATIENTS AND METHODS: A pharmaco-epidemiological study based on the Norwegian Prescription Database and Cancer Registry of Norway. The 1-year periodic prevalence of receiving different analgesics and of persistent opioid use were analyzed. Persistent opioid use was defined as >365 Defined Daily Doses or >9000 mg Oral Morphine Equivalents during 365 days with prescriptions in all quarters of the 365 days period. Data were reported for the first 7 years for patients who lived 8-9 years after cancer diagnosis (N = 1502), while for patients who lived 6-7 years (N = 3817) data was reported for the first 5 years after diagnosis. RESULTS: Compared to age- and gender adjusted general population, the 1-year periodic prevalence of opioid prescription was doubled the first year after diagnosis and remained raised with approximately 50%. The prevalence of persistent opioid use was threefold of the general population. Approximately 55% of patients with persistent opioid use 4 years after a cancer diagnosis were co-medicated with high doses of benzodiazepines and/or benzodiazepine-related hypnotics. CONCLUSION: The findings of increased opioid use raise concerns regarding whether the benefits outweigh risks and side effects in this population.

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.

Prescription of analgesics to long-term survivors of cancer in early adulthood, adolescence, and childhood in Norway: a national cohort study.

Increasing numbers survive cancers in childhood and adolescence. Long-term survivors of cancers in adulthood have increased prevalence of pain and consumption of analgesics. It is not established whether long-term survivors of cancers in childhood and adolescence also have an increased use of analgesics. However, based on increased use of antidepressants and anxiolytics in long-term survivors of cancers in childhood and adolescence, we hypothesized that this group also had increased use of analgesics. Based on data from the 2 nationwide registers, the Cancer Registry of Norway and the Norwegian Prescription Database, a cohort of 5585 (52% males) long-term survivors of cancers in childhood, adolescence, and early adult life was established. Age- and sex-adjusted comparisons were made to the general population. The age-adjusted one-year periodic prevalence of receiving prescriptions of opioids, benzodiazepines, and benzodiazepine-related hypnotics in the study population was increased by 20% to 50%, and the one-year periodic prevalence of receiving prescriptions of gabapentinoids was approximately increased 2-fold compared to the general population. For paracetamol and nonsteroidal anti-inflammatory drugs, no difference was found. For those survivors, who were persistent or high-dose users of opioids, comedication with high doses of benzodiazepines and/or benzodiazepine-related hypnotics was far more common than among persistent and high-dose opioid users in the general population. The high prevalence of gabapentinoids may indicate increased prevalence of neuropathic pain in this group. The high degree of comedication with benzodiazepines and/or benzodiazepine-related hypnotics in survivors on persistent and high-dose opioids might be an indication of problematic opioid use or addiction.

Tramadol use in Norway: A register-based population study.

PURPOSE: Increasing use of tramadol for chronic non-cancer pain is concerning since tramadol users may be at risk of developing recurrent opioid use with increasing opioid consumption and co-medication. Therefore, we investigated a complete national cohort of tramadol users. METHODS: The study population (154 042 adult individuals in Norway, who redeemed ≥ one tramadol prescription in 2012) was stratified into four groups according to their opioid use 2 years before their first tramadol prescription in 2012 and followed until 2016. Information on all dispensed opioid analgesics, benzodiazepines (BZDs), and BZD-related Z-hypnotics were retrieved from the Norwegian Prescription Database. RESULTS: Six percent of opioid naïve tramadol users (no opioid use 2 years before tramadol use in 2012) became recurrent users (received opioids annually during 4-year follow-up), almost doubled their mean opioid consumption (66 to 108 defined daily doses [DDD]). One-quarter proceeded to strong opioids or was co-medicated with BZDs, one-third with Z-hypnotics. Among former weak opioid users, 39.8% became recurrent users, 18.7% proceeded to strong opioids, mean opioid consumption increased slightly, one-third used BZDs, or Z-hypnotics concurrently. Among former strong opioid and users in palliative care; 61%, 70% became recurrent users and developed a similar prescription pattern (high and increasing mean opioid consumption, 301 to 318, 413 to 430 DDD); half of them proceeded to strong opioids and/or used BZDs or Z-hypnotics concurrently. CONCLUSIONS: Many patients who developed recurrent opioid use received prescriptions which substantially conflicted with existing guidelines and might lead to problematic opioid use.

A complete national cohort study of prescriptions of analgesics and benzodiazepines to cancer survivors in Norway 10 years after diagnosis.

Chronic pain due to surgery, radiotherapy, or chemotherapy is prevalent in long-term cancer survivors. Chronic pain due to successful cancer treatment should be treated as chronic nonmalignant pain, primarily with nonpharmacological strategies. Based on complete national data from the Cancer Registry of Norway and the Norwegian prescription database, the aim of this study was to compare the use of nonopioid analgesics, opioids, and benzodiazepines 10 years after cancer diagnosis in long-term cancer survivors and the age- and sex-adjusted general population. The 1-year periodic prevalence of use was higher in long-term cancer survivors in all the studied drug classes: opioids (143.5 vs 129.6/1000), paracetamol (88.3 vs 80.7/1000), nonsteroidal anti-inflammatory drugs (229.1 vs 221.7), gabapentinoids (13.4 vs 10.0/1000), benzodiazepines (88.3 vs 77.9/1000), and benzodiazepine-like hypnotics (118.1 vs 97.4/1000). The prevalence of persistent and high-dose opioid use (>365 defined daily doses [DDDs] and >730 DDDs, respectively, during 365 days, and prescriptions all quarters of the year) was also higher in the cancer survivors than in the general population (6.5 vs 4.8/1000 for persistent use and 2.7 vs 1.3/1000 for high-dose use). Less than 10% of persistent and high-dose users received only long-acting opioid formulations. Furthermore, most long-term cancer survivors with persistent or high-dose opioid use were also high-dose users (>100 DDDs/year) of either benzodiazepines or benzodiazepine-like hypnotics. It is an issue of concern that most of those using opioids did not adhere to guidelines regarding opioid formulation and comedication with other drugs with addictive properties.