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.

Patient Reported Outcome Measures in Chronic Neuropathic Pain Clinical Trials - A Systematic Literature Review.

In neuropathic pain clinical trials, the patient's perspective is often insufficiently reflected focusing mainly on pain intensity. Comparability of outcome assessment is limited due to heterogenous patient reported outcome measures (PROMs). The MEDLINE, CENTRAL, and Embase databases and reference lists of published meta-analyses were searched. Randomized controlled studies assessing treatment efficacy of drugs for chronic neuropathic pain were included. PROMs were assigned to recommended IMMPACT/NeuPSIG domains: pain intensity, pain other aspects, physical functioning, emotional functioning, global improvement and satisfaction, adverse events, participant disposition. Domains and PROMs were compared regarding the publication year and methodological quality of the studies. Within the 251 included studies 200 PROMs were used with 27 being recommended by IMMPACT/NeuPSIG. The number of domains was higher in high/moderate quality studies. The (sub-) domains 'physical functioning', 'global improvement and satisfaction', and 'neuropathic pain quality' were assessed more frequently in high/moderate quality studies and those published after 2011. Recent studies and those of better quality more often used the recommended PROMs. Although neuropathic assessment via PROMs has improved, there is still a high heterogeneity. A standardized core set of outcome domains and should be defined to improve neuropathic pain treatment and to achieve better comparability of clinical trials. Perspective: This systematic literature review assesses the use of patient reported outcome measures (PROMs) in chronic neuropathic pain. The results show that there is still a high heterogeneity, highlighting the need for a standardized core set of outcome domains and PROMs to improve comparability of clinical trials and neuropathic pain treatment.

Preventing Post Dural Puncture Headache after Intrathecal Drug Delivery System Implantation Through Preventive Fibrin Glue Application: A Retrospective Study.

BACKGROUND: Cerebrospinal fluid (CSF) leakage resulting in post dural puncture headache (PDPH) is a frequent adverse effect observed after intrathecal drug delivery system (IDDS) implantation. CSF leakage symptoms negatively affect patient quality of life and can result in additional complications. Fibrin glue was used to treat CSF leakage syndrome. We developed a procedure to reduce the incidence of PDPH by preventing CSF leakage with the use of fibrin glue during surgery. OBJECTIVES: The main outcome criterion for this study was the incidence of PDPH syndrome after IDDS implantation with or without preventive fibrin glue application during the procedure. STUDY DESIGN: We designed a monocentric retrospective cohort study to compare the incidence of PDPH due to CSF leakage syndrome after lumbar puncture in patients with an implanted intrathecal pump, with or without preventive fibrin glue application during the procedure. SETTING: The study was held in the Anesthesiology and Pain department of the  Integrative Cancer Institute (ICO), Angers - France. METHODS: The study compared 2 patient cohorts over 2 successive periods. Fibrin glue was injected into the introducer needle puncture pathway after placement of the catheter immediately following needle removal. RESULTS: The no-glue group included 107 patients, whereas the glue group included 92 patients.Two application failures were observed (2.04%). Fibrin glue application results in a significant decrease in PDPH incidence, from 32.7% in the no-glue group to 10.92 % (P < 0.001) in the glue group. In regard to severity, in the no-glue group, 37.1% of PDPH syndromes were mild, 34.3% were moderate, and 28.6% were severe. In the fibrin glue group, 80% of PDPH syndromes were mild, and 20% were moderate. No severe PDPHs were reported after fibrin glue application. Duration of symptoms was also statistically shorter in the fibrin glue group (maximum of 3 days vs. 15 days in the no-glue group). In a univariate analysis, preventive fibrin glue application and age are significant to prevent PDPH. In multivariate analysis, only fibrin glue application was statistically significant (odds ratio, 0.26; P = 0.0008). No adverse effects linked to fibrin glue were observed. LIMITATIONS: The main limitation of this study is its retrospective nature. In addition, this study is from a single center with a potential selection bias and a center effect. CONCLUSIONS: The novel use of fibrin glue is promising in terms of its effect on PDPH and its safety profile. Its moderate cost and reproducibility make it an affordable and efficient technique.