Optimizing Initial Intrathecal Drug Ratio for Refractory Cancer-Related Pain for Early Pain Relief. A Retrospective Monocentric Study.

OBJECTIVE: Intrathecal (IT) drug delivery has shown its efficiency in treating refractory cancer pain, but switching opioids from the systemic to the intrathecal route is a challenging phase. Moreover, associations are widely used and recommended. Few data deal with the initial dosage of each drug. Analyzing conversion factors and initial dosages used in intrathecal therapy seems essential to decreasing the length of titration and to delivering quick pain relief to patients. METHODS: We retrospectively analyzed data from consecutive adult patients implanted with an intrathecal device for cancer pain and treated at the Institut de Cancérologie de l'Ouest, in Angers, France, for four years. The main goal was to identify factors associated with early pain relief after intrathecal drug delivery system (IDDS) implantation. RESULTS: Of the 220 IDDS-treated patients, 70 (32%) experienced early pain relief (EaPR) and 150 (68%) delayed pain relief (DePR). Performance Status stage and initial IT ropivacaine:IT morphine ratio were the variables independently associated with EaPR. The best IT ropivacaine:IT morphine ratio to predict EaPR was 5:1, with a 73% (95% confidence interval [CI] = 64.8% to 79.6%) sensitivity and a 67.1% (95% CI = 54.9% to 77.9%) specificity. EaPR subjects experienced better pain relief (-84% vs -60% from baseline pain score, P < 0.0001), shorter length of hospitalization (7 vs 10 days, P < 0.0001), and longer survival (155 vs 82 days, P = 0.004). CONCLUSIONS: Local anesthetic:morphine ratio should be considered when starting IDDS treatment. EaPR during the IT analgesia titration phase was associated with better pain relief and outcomes in patients with refractory cancer-related pain.

Intrathecal Drug Delivery Systems for Refractory Pancreatic Cancer Pain: Observational Follow-up Study Over an 11-Year Period in a Comprehensive Cancer Center.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death in Europe and the United States. Studies have demonstrated that patients with pancreatic cancer have a high prevalence of pain, with rates varying from 47% to 82%. Analgesia using intrathecal drug delivery systems (IDDS) has been poorly studied specifically in this population. METHODS: The IDDS for pancreatic cancer pain was a follow-up observational study designed to evaluate 11-year results of IDDS for refractory pancreatic cancer pain at the Institut de Cancérologie de L'Ouest, Paul Papin in France. Patients were followed from March 2006 to April 2017. Patients were selected for IDDS based on multidisciplinary meeting discussion. All IDDS-treated patients were prescribed a combined intrathecal analgesics regimen through a catheter placed according to painful metameric level. Postimplant assessment of pain was determined using a numerical rating scale (NRS). Patients were followed via day-hospital visits and telephone calls at least monthly until death. Pain scores were compared using the Wilcoxon signed rank test. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between groups by log rank tests. RESULTS: Ninety-three patients received IDDS, and total therapy duration accounts for 10,300 IDDS days. Implanted patients suffered from severe pain before implantation (median presurgical NRS, 8 [interquartile range, 7-9]) despite a median 360 mg (260-600) oral morphine equivalent daily dose. Median OS in the whole cohort after intrathecal treatment start was 82 days (95% confidence interval, 59-95). Median OS after surgery for implantable pump was 91 days (83-111) and for external pump 27 days (20-49; P < .0001). IDDS was associated with pain relief with a significant statistical difference between preimplantation NRS pain score and 1 week (median, -6 [-7 to -4]; P < .001), 1 month (median, -5 [-6 to -3]; P < .001), and 3 months (median, -6 [-7 to -4]; P < .001). Severe pain (NRS score, ≥7) decreased from 89.2% before surgery to 4.5% after 1 week, 6.7% after 1 month, and 10.3% after 3 months of IDDS implant (P < .01). Global complications rate was low, consistent with published literature. CONCLUSIONS: Despite our study's limitations, results suggest that long-term IDDS for refractory malignant pain due to pancreatic cancer was both efficacious and safe in pancreatic cancer pain. We have demonstrated, in the largest series of IDDS for pancreatic cancer pain reported yet, a clinically and statistically significant pain reduction in patients receiving IDDS.

A double-blind randomized trial of wound and intercostal space infiltration with ropivacaine during breast cancer surgery: effects on chronic postoperative pain.

BACKGROUND: The efficacy of local anesthetic wound infiltration for the treatment of acute and chronic postoperative pain is controversial and there are no detailed studies. The primary objective of this study was to evaluate the influence of ropivacaine wound infiltration on chronic pain after breast surgery. METHODS: In this prospective, randomized, double-blind, parallel-group, placebo-controlled study, 236 patients scheduled for breast cancer surgery were randomized (1:1) to receive ropivacaine or placebo infiltration of the wound, the second and third intercostal spaces and the humeral insertion of major pectoralis. Acute pain, analgesic consumption, nausea and vomiting were assessed every 30 min for 2 h in the postanesthesia care unit and every 6 h for 48 h. Chronic pain was evaluated 3 months, 6 months, and 1 yr after surgery by the brief pain inventory, hospital anxiety and depression, and neuropathic pain questionnaires. RESULTS: Ropivacaine wound infiltration significantly decreased immediate postoperative pain for the first 90 min, but did not decrease chronic pain at 3 months (primary endpoint), or at 6 and 12 months postoperatively. At 3 months, the incidence of chronic pain was 33% and 27% (P = 0.37) in the ropivacaine and placebo groups, respectively. During follow-up, brief pain inventory, neuropathic pain, and anxiety increased over time in both groups (P < 0.001) while depression remained stable. No complications occurred. CONCLUSION: This multicenter, prospective study shows that ropivacaine wound infiltration after breast cancer surgery decreased immediate postoperative pain but did not decrease chronic pain at 3, 6, and 12 months postoperatively.

Prolonged perioperative thoracic epidural analgesia may improve survival after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A comparative study.

OBJECTIVE: To assess the effectiveness of prolonged perioperative thoracic epidural analgesia (PEA) on long term survival of patients who underwent a complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM). BACKGROUND: Grade III-IV morbidity affects long term outcomes after CRS and HIPEC. As compared with opioid administered via patient-controlled analgesia (PCA), PEA reduces morbidity. METHOD: From 2005 to 2016, 150 patients underwent CRS plus HIPEC with or without prolonged PEA. Clinical data and outcomes collected from prospective database were analyzed. Survival was assessed in terms of analgesic method using Kaplan-Meier plots and a propensity score. RESULTS: Patients 'characteristics of 59 patients in PCA group were comparable to those of 91 patients in PEA group, except for age, ASA score and fluid requirements, significantly more important in PEA group. Grade III-IV morbidity was 62.7% in PCA group compared with 36.3% in PEA group (p = 0.0015). Median overall survival (OS) of PEA group was 54.7 months compared to 39.5 months in PCA group (p = 0.0078). When adjusted on the covariates, using the propensity score, the PEA significantly improves OS [HR 0.40 (95% CI: 0.28-0.56)] (p < 0.0001) and disease free survival (DFS) [HR 0.61 (95% CI: 0.45-0.81] (p < 0.0007) CONCLUSIONS: In this retrospective study of patients who underwent a complete CRS and HIPEC for colorectal peritoneal metastases, the perioperative thoracic epidural analgesia prolonged for over 72 h reduced significantly the grade III-IV morbidity and may improve OS and DFS.

Patient satisfaction and acceptance of their totally implanted central venous catheter: a French prospective multicenter study.

INTRODUCTION: Most cancer patients require a totally implanted central venous catheter (TIVAD) for their treatment. In a previous study, we developed and validated a questionnaire dubbed QASICC (Questionnaire for Acceptance of, and Satisfaction with, Implanted Central Venous Catheter) assessing patient satisfaction with, and acceptance of, their TIVAD. In the present study, we conducted a large, prospective, multicenter study in cancer patients aimed to analyze factors that could influence patients' acceptance of, and satisfaction with, their device. METHODS: The QASICC is composed of 22 items assessing 5 dimensions. The construction and validation of the questionnaire was achieved using validated methodology to determine its psychometric characteristics. The questionnaire was submitted to 720 patients in 11 French institutions; 567 answers were analyzed. RESULTS: Younger patients had the most difficulties in coping with their TIVAD, especially regarding daily activities and their body image and private life compared to older patients. Sex was significantly related to patient satisfaction, with worse scores in women. Breast tumor location was also correlated with low TIVAD acceptance. TIVAD on the right side also positively influenced satisfaction and acceptance of the device. CONCLUSIONS: QASICC has proved to be efficient, and to detect known issues regarding daily activities and body image. As our population was mostly composed of women with breast cancer, our results reflect specific aspects of this population. The TIVAD remains generally well-accepted and our questionnaire should help health-care workers to better address the specific needs of their patients based on the answers provided.

Rationale for Prospective Assays of Intrathecal Mixtures Including Morphine, Ropivacaine and Ziconotide: Prevention of Adverse Events and Feasibility in Clinical Practice.

BACKGROUND: Use of intrathecal admixtures is widespread, but compounding these is sometimes challenging and may result in errors and complications causing super-potency or sub potency adverse events in patients or malfunctions in the pump itself. OBJECTIVE: The purpose of this study is to evaluate the accuracy of compounding of intrathecal admixtures through a prospective, systematic quantitative analysis of each component of the mixture before delivery to patients. STUDY DESIGN: Observational follow up prospective study of intrathecal mixtures components concentrations before refills. SETTINGS: Assays were performed on all intrathecal admixtures produced by the ICO-Paul Papin compounding pharmacy between January 2013 and October 2014 using Ultra High Performance Liquid Chromatography (U.H.P.L.C.). In addition, pH levels of admixtures have been measured since June 2014. When measured concentrations were 15% above or below the required concentrations, the mixture was excluded and compounded again. RESULTS: 1729 mixtures were analyzed. Mean deviation from theoretical values was -1.17% ± 0.28% for morphine, -0.95% ± 1.07% for ropivacaine, and 4.82% ± 0.6% for ziconotide. Exclusion rates were 8.33% overall, but fell from 11.67% in 2013 to 4.97% in 2014. Most exclusions were caused by inaccuracy in the dose of ziconotide. Average mixture pH of the 603 tested admixtures was 4.83 ± 0.6%. LIMITATIONS: This study is monocentric and limitations include also its non-randomized nature with no clinical comparison of the rate of adverse events with a refill process without control of each component concentrations. CONCLUSION: Prospective assays provide benefits in ensuring accuracy of intrathecal mixture compounding and in preventing overdosing or sub dosing, most notably concerning Ziconotide.

[Multicenter validation study of a questionnaire assessing patient satisfaction with and acceptance of totally-implanted central venous access devices]. / Validation multicentrique d'un questionnaire évaluant l'acceptation et la satisfaction des patients porteurs de chambre à cathéter implantable : le questionnaire QASICC.

OBJECTIVE: Most cancer patients require a totally-implanted central venous access device (TIVAD) for their treatment. This was a prospective, multicenter, open study to: (i) develop and validate a French-language questionnaire dubbed QASICC (Questionnaire for Acceptance of and Satisfaction with Implanted Central Venous Catheter) assessing patient's satisfaction with and acceptance of their TIVAD; (ii) develop a mean score of patient's acceptance and satisfaction; (iii) look for correlation between QASICC score and TIVAD patient/tumor pathology/device characteristics. METHODS: From 2011 November to 2012 December, the first version of the QASICC questionnaire that included 27 questions assessing seven dimensions was re-tested among 998 cancer patients in eleven French cancer hospitals (eight cancer research institutes and three university/general hospitals). The goal was: (i) to reduce the questionnaire item and dimension number (pertinency, saturation effect, item correlation); (ii) to assess its psychometric properties, demonstrate its validity and independency compared to (EORTC) QLQC30; (iii) to correlate clinical and pathological patient's/tumor's/TIVAD's parameters with the QASICC questionnaire score (the higher the overall score, the greater the acceptance and satisfaction). The questionnaire was administered to the patient 30 days (±15 days) after TIVAD's implantation. RESULTS: Among 998 questionnaires given to cancer patients, 658 were analyzed and 464 were fully assessed as there was no missing data. Time to fill-in the questionnaire was five minutes in 90% patients. Final QASICC tool included twenty-two questions assessing four homogeneous dimensions (65%