A qualitative evaluation of the oncologists', neurologists', and pain specialists' views on the management and care of chemotherapy-induced peripheral neuropathy in The Netherlands.

PURPOSE: In treating cancer, different chemotherapy regimens cause chemotherapy-induced peripheral neuropathy (CIPN). Despite recent international guidelines, a gold standard for diagnosis, treatment, and care is lacking. To identify the current clinical practice and the physicians' point of view and ideas for improvement, we evaluated CIPN care by interviewing different specialists involved. METHODS: We performed semi-structured, audio-recorded, transcribed, and coded interviews with a purposive sample of oncologists, pain specialists, and neurologists involved in CIPN patients' care. Data is analyzed by a constant comparative method for content analysis, using ATLAS.ti software. Codes, categories, and themes are extracted, generating common denominators and conclusions. RESULTS: With oncologists, pain specialists, and neurologists, nine, nine, and eight interviews were taken respectively (including three, two, and two interviews after thematic saturation occurred). While useful preventive measures and predictors are lacking, patient education (e.g., on symptoms and timely reporting) is deemed pivotal, as is low-threshold screening (e.g., anamnesis and questionnaires). Diagnosis focusses on a temporal relationship to chemotherapy, with adjuvant testing (e.g., EMG) used in severe or atypical cases. Symptomatic antineuropathic and topical medication are often prescribed, but personalized and multidimensional care based on individual symptoms and preferences is highly valued. The limited efficacy of existing treatments, and the lack of standardized protocols, interdisciplinary coordination, and awareness among healthcare providers pose significant challenges. CONCLUSION: Besides the obvious need for better therapeutic options, and multidisciplinary exploration of patients' perspectives, a structured and collaborative approach towards diagnosis, treatment, referral, and follow-up, nurtured by improving knowledge and use of existing CIPN guidelines, could enhance care.

Pharmacological prevention and treatment of opioid-induced constipation in cancer patients: A systematic review and meta-analysis.

BACKGROUND: Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients. METHODS: A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed. RESULTS: Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I2 = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I2 = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I2 = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I2 = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates. CONCLUSIONS: Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.

Magnesium hydroxide versus macrogol/electrolytes in the prevention of opioid-induced constipation in incurable cancer patients: study protocol for an open-label, randomized controlled trial (the OMAMA study).

BACKGROUND: Opioid-induced constipation (OIC) is a common symptom in cancer patients treated with opioids with a prevalence of up to 59%. International guidelines recommend standard laxatives such as macrogol/electrolytes and magnesium hydroxide to prevent OIC, although evidence from randomized controlled trials is largely lacking. The aim of our study is to compare magnesium hydroxide with macrogol /electrolytes in the prevention of OIC in patients with incurable cancer and to compare side-effects, tolerability and cost-effectiveness. METHODS: Our study is an open-label, randomized, multicenter study to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. In total, 330 patients with incurable cancer, starting with opioids for pain management, will be randomized to treatment with either macrogol/electrolytes or magnesium hydroxide. The primary outcome measure is the proportion of patients with a score of < 30 on the Bowel Function Index (BFI), measured on day 14. The Rome IV criteria for constipation, side effects of and satisfaction with laxatives, pain scores, quality of life (using the EQ-5D-5L), daily use of laxatives and escape medication, and cost-effectiveness will also be assessed. DISCUSSION: In this study we aim to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. The outcome of our study will contribute to prevention of OIC and scientific evidence of guidelines on (opioid-induced) constipation. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov: NCT05216328 and in the Dutch trial register: NTR80508. EudraCT number 2022-000408-36.

Postoperative pain assessment in hospitalised patients: National survey and secondary data analysis.

BACKGROUND: Measuring pain is important for the adequate pain management of postoperative patients. The actual compliance with pain assessment in postoperative patients after implementation of a national safety program is unknown. OBJECTIVES: The aim of this study is to examine the compliance with pain assessment in postoperative patients after implementation of a national safety program, according to the national quality indicators for pain assessment in postoperative patients. Furthermore, organisational factors associated with this compliance were determined. STUDY DESIGN: In this study, two data sources were used: 1) data from an evaluation study of the Dutch Hospital Patient Safety Program; and 2) data from a questionnaire survey. METHODS: The compliance with two different pain process indicators was determined: 1) 3 pain measurements a day, all three full days after surgery; and 2) ≥1 pain measurement a day, all three full days after surgery. Multilevel logistic regression analysis was used to investigate the association between organisational factors in hospitals and compliance with pain process indicators. RESULTS: Data of 3895 patient records from 16 hospitals was included in this study. In 12% of the postoperative patients, pain was measured 3 times a day, all three full days after surgery. In 53% of the postoperative patients, pain was measured ≥1 time a day, all three full days after surgery. Compliance was highest in general hospitals compared to tertiary teaching and academic hospitals, and was statistically significantly higher at the surgery and surgical oncology department compared to the other departments. CONCLUSIONS: Low compliance was shown with pain assessment in postoperative patients, according to the process indicator pain after surgery in Dutch hospitals. This suggests that the implementation of measuring pain in hospitals is still insufficient.

The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain.

INTRODUCTION: The neuroinflammatory response plays a key role in several pain syndromes. Intravenous (iv) lidocaine is beneficial in acute and chronic pain. This review delineates the current literature concerning in vitro mechanisms and in vivo efficacy of iv lidocaine on the neuroinflammatory response in acute and chronic pain. DATABASES AND DATA TREATMENT: We searched PUBMED and the Cochrane Library for in vitro and in vivo studies from July 1975 to August 2014. In vitro articles providing an explanation for the mechanisms of action of lidocaine on the neuroinflammatory response in pain were included. Animal or clinical studies were included concerning iv lidocaine for acute or chronic pain or during inflammation. RESULTS: Eighty-eight articles regarding iv lidocaine were included: 36 in vitro studies evaluating the effect on ion channels and receptors; 31 animal studies concerning acute and chronic pain and inflammatory models; 21 clinical studies concerning acute and chronic pain. Low-dose lidocaine inhibits in vitro voltage-gated sodium channels, the glycinergic system, some potassium channels and Gαq-coupled protein receptors. Higher lidocaine concentrations block potassium and calcium channels, and NMDA receptors. Animal studies demonstrate lidocaine to have analgesic effects in acute and neuropathic pain syndromes and anti-inflammatory effects early in the inflammatory response. Clinical studies demonstrate lidocaine to have advantage in abdominal surgery and in some neuropathic pain syndromes. CONCLUSIONS: Intravenous lidocaine has analgesic, anti-inflammatory and antihyperalgesic properties mediated by an inhibitory effect on ion channels and receptors. It attenuates the neuroinflammatory response in perioperative pain and chronic neuropathic pain.

Chronic post-thoracotomy pain: a retrospective study.

BACKGROUND: Chronic pain is common after thoracotomy. The primary goal of this study was to investigate the incidence of chronic post-thoracotomy pain. The secondary goal was to identify possible risk factors associated with the development of chronic post-operative pain. METHODS: We contacted 255 patients who had undergone a classic postero-lateral thoracotomy at our institution in the period between January 2001 and December 2003. All patients received a letter requesting participation; a questionnaire was included with the letter. One week later patients were contacted by telephone to obtain the answers to the questionnaire. RESULTS: We ultimately obtained results from 149 patients (58% of all thoracotomies, 84% of survivors). The overall incidence of chronic post-operative pain was 52% (32% mild, 16% moderate and 3% severe chronic post-operative pain). Patients with chronic post-operative pain reported acute post-operative pain more frequently than those without (85% vs. 62%, P = 0.01), had more severe acute post-operative pain (P = 0.0001), underwent more extensive surgical procedures (P = 0.01), had more constant acute pain (vs. fluctuating pain or pain in attacks) (P = 0.0004) and reported less absence of pain during the first post-operative week (P = 0.0001). There was no significant decrease in chronic pain with time after thoracotomy. CONCLUSION: Our study confirms that chronic post-thoracotomy pain is a common problem. The results from our study suggest that chronic post-thoracotomy pain may be associated with more intensive and extensive nociceptive input due to thoracic surgery.