Avoiding Catch-22: validating the PainDETECT in a in a population of patients with chronic pain.

BACKGROUND: Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system and is a major therapeutic challenge. Several screening tools have been developed to help physicians detect patients with neuropathic pain. These have typically been validated in populations pre-stratified for neuropathic pain, leading to a so called "Catch-22 situation:" "a problematic situation for which the only solution is denied by a circumstance inherent in the problem or by a rule". The validity of screening tools needs to be proven in patients with pain who were not pre-stratified on basis of the target outcome: neuropathic pain or non-neuropathic pain. This study aims to assess the validity of the Dutch PainDETECT (PainDETECT-Dlv) in a large population of patients with chronic pain. METHODS: A cross-sectional multicentre design was used to assess PainDETECT-Dlv validity. Included where patients with low back pain radiating into the leg(s), patients with neck-shoulder-arm pain and patients with pain due to a suspected peripheral nerve damage. Patients' pain was classified as having a neuropathic pain component (yes/no) by two experienced physicians ("gold standard"). Physician opinion based on the Grading System was a secondary comparison. RESULTS: In total, 291 patients were included. Primary analysis was done on patients where both physicians agreed upon the pain classification (n = 228). Compared to the physician's classification, PainDETECT-Dlv had a sensitivity of 80% and specificity of 55%, versus the Grading System it achieved 74 and 46%. CONCLUSION: Despite its internal consistency and test-retest reliability the PainDETECT-Dlv is not an effective screening tool for a neuropathic pain component in a population of patients with chronic pain because of its moderate sensitivity and low specificity. Moreover, the indiscriminate use of the PainDETECT-Dlv as a surrogate for clinical assessment should be avoided in daily clinical practice as well as in (clinical-) research. Catch-22 situations in the validation of screening tools can be prevented by not pre-stratifying the patients on basis of the target outcome before inclusion in a validation study for screening instruments. TRIAL REGISTRATION: The protocol was registered prospectively in the Dutch National Trial Register: NTR 3030 .

Optimal dose of intrathecal isobaric bupivacaine in total knee arthroplasty.

PURPOSE: Early mobilization is an important aspect of fast-track protocols and intrathecal bupivacaine is often used in primary total knee arthroplasty (TKA). Although the optimal dose is not known, conventional doses leave patients unable to mobilize for two to four hours. The dose of an intrathecally administered local anesthetic should therefore be optimized to achieve immediate postoperative mobilization. This study determined the median effective dose (ED) of intrathecal bupivacaine for primary unilateral TKA. METHODS: Between April 2016 and February 2017 all patients who qualified for unilateral primary TKA were eligible for inclusion. In this dose-finding study, the up-and-down method by Dixon and Massey was used, which is a sequential allocation model. Patients received a dose of isobaric bupivacaine according to the outcome of the preceding patient with an initial starting dose of 5 mg. The dose was increased or decreased by steps of 0.5 mg, depending on the outcome of the preceding patient. During surgery, patients were closely monitored for indications of pain. Time points of regaining motor and sensory functions were determined. RESULTS: Twenty-five patients were included. Mean (SD) age was 70.1 (8.8) yr old, median [IQR] body mass index was 29.5 [27.3-30.9 kg·m-2], and 48% were female. In 11 patients the dose was inadequate; of these, nine patients needed additional anesthesia during surgery, and in four of these nine patients a conversion to general anesthesia was required. The median ED was 3.5 (95% confidence interval [CI], 3.1 to 4.0) mg of intrathecal bupivacaine. The calculated ED50 was 3.4 (95% CI, 2.7 to 4.0) mg; the calculated ED95 was 5 (95% CI, 3.7 to 8.0) mg. CONCLUSION: In this small study with tight control over operative duration, the median effective dosage of intrathecal isobaric bupivacaine for primary unilateral TKA was 3.5 mg and the ED95 was 5 mg. Reduction of conventional dosages of intrathecal bupivacaine is feasible at centres using fast-track arthroplasty protocols.

Optimizing the dose of local infiltration analgesia and gabapentin for total knee arthroplasty, a randomized single blind trial in 128 patients.

BACKGROUND AND PURPOSE: Effective analgesia is essential for postoperative recovery and rehabilitation in TKA. The challenge of analgesic regimes is to obtain adequate pain relief and maximum muscle control to mobilize and rehabilitate patients early. However, the optimal dose and best composition are not known. We hypothesized that there would be no differences in reported postoperative pain on the day of the TKA surgery as well as the first day after surgery when different combinations of ropivacain for LIA and gabapentin are given. METHODS: This prospective randomized trial examined 128 TKA patients treated with LIA and gabapentin in four groups. Group A: 300-mg ropivacain/600-300-300-mg gabapentin. Group B: 150-mg ropivacain/600-300-300-mg gabapentin. Group C: 300-mg ropivacain/300-100-100-mg gabapentin. Group D: 150-mg ropivacain/300-100-100-mg gabapentin. Primary endpoint was pain (NRS) at multiple moments. Secondary endpoints were number of adverse effects, length of hospital stay (LOS), the amount of consumption of pain medication, and wound leakage. Generalized estimating equation (GEE) was used to detect differences between the four groups regarding the course of pain. RESULTS: No differences regarding adverse effects, LOS, and wound leakage were found. GEE revealed a significant difference in course of pain between group A and B, with group B experiencing higher NRS scores postoperatively than group A (p=0.021). No differences between the other groups were found. INTERPRETATION: The results of the current study suggest that LIA with 300-mg (150ml) ropivacain might be more effective than 150-mg (75ml) ropivacain. Alteration in dose of gabapentin appears not to have influence on the course of pain.

Investigating the validity of the DN4 in a consecutive population of patients with chronic pain.

Neuropathic pain is clinically described as pain caused by a lesion or disease of the somatosensory nervous system. The aim of this study was to assess the validity of the Dutch version of the DN4, in a cross-sectional multicentre design, as a screening tool for detecting a neuropathic pain component in a large consecutive, not pre-stratified on basis of the target outcome, population of patients with chronic pain. Patients' pain was classified by two independent (pain-)physicians as the gold standard. The analysis was initially performed on the outcomes of those patients (n = 228 out of 291) in whom both physicians agreed in their pain classification. Compared to the gold standard the DN4 had a sensitivity of 75% and specificity of 76%. The DN4-symptoms (seven interview items) solely resulted in a sensitivity of 70% and a specificity of 67%. For the DN4-signs (three examination items) it was respectively 75% and 75%. In conclusion, because it seems that the DN4 helps to identify a neuropathic pain component in a consecutive population of patients with chronic pain in a moderate way, a comprehensive (physical-) examination by the physician is still obligate.

Which patient-specific and surgical characteristics influence postoperative pain after THA in a fast-track setting?

BACKGROUND: In our hospital a fast-track setting including a multimodal pain protocol is used for total hip arthroplasty (THA). Despite this multimodal pain protocol there is still a large range in reported postoperative pain between patients, which hinders mobilization and rehabilitation postoperatively. The goal of this study was to identify which patient-specific and surgical characteristics influence postoperative pain after THA in a fast-track setting. METHODS: All 74 patients with osteoarthritis of the hip who underwent primary THA procedure by anterior supine intermuscular approach between November 2012 and January 2014 were included in this prospective cohort study. The protocol for pain medication was standardized. Postoperative pain determined with the Numeric Rating Score was collected at 17 standardized moments. Linear mixed models were used to examine potential patient-specific and surgical factors associated with increased postoperative pain. RESULTS: Pain patterns differed substantially across individuals. Adjusted for other variables in the model, preoperative use of pain medication (regression coefficient 0.78 (95% CI 0.28-1.26); p = 0.005) and preoperative neuropathic pain scored by DN4 (regression coefficient 0.68 (95% CI 0.15-1.20); p = 0.02) were the only factors significantly associated with higher postoperative pain scores. CONCLUSIONS: The knowledge of which factors are associated with higher postoperative pain scores after THA in a fast-track setting may help optimizing perioperative postoperative pain management and preoperative education of these patients. TRIAL REGISTRATION: The study was retrospectively registered in the ISRCTN registry under identifier ISRCTN15422220 (date of registration: July 25, 2017).

High Body Mass Index Is a Potential Risk Factor for Persistent Postoperative Pain after Breast Cancer Treatment.

BACKGROUND: Risk factors associated with persistent pain after breast cancer treatment are needed to develop prevention and treatment strategies to improve the quality of life for patients with breast cancer. OBJECTIVES: To identify factors associated with persistent pain in women undergoing breast cancer treatments. STUDY DESIGN: Retrospective study. SETTING: Regional hospital in the Netherlands. METHODS: The primary outcome was pain associated with surgery at more than 6 months postoperatively and patients were stratified based on the associated visual analog" scale score they reported: reporting no pain as "no pain," pain 1 - 29 mm as "mild pain," and pain 30 - 100 mm as "moderate/severe pain." Secondary outcomes were function, symptom, and total quality of life scores. Predefined risk factors analyzed for association with outcomes included: age, smoking status, diabetes, body mass index (BMI), disease stage, surgery type, axillary lymph node dissection, reoperation, chemotherapy, radiotherapy, and hormone therapy. RESULTS: Of the 718 patients who were approached, 492 were included (follow-up 2.5 ± 1.8 years). Thirty-five percent of patients developed persistent pain (n = 122 "mild pain," n = 53 "moderate/severe pain'"). Age, BMI, surgery type, axillary lymph node dissection, disease stage, reoperation, chemotherapy, and radiotherapy were identified as potential risk factors in univariate ordinal regression analyses (P < 0.10). Age (P < 0.01) and BMI (P = 0.04) remained independently predictive in the multivariate model. BMI and age were associated with odds ratios (ORs) of 1.04 (95% confidence intervals (CI): 1.00 - 1.08) and 0.97 (95% CI: 0.95 - 0.99), respectively per point and year increase. BMI was associated with a higher symptom score (r = 0.14, P < 0.01), a lower level of function (r = -0.11, P = 0.01), and lower total quality of life scores (r = -0.13, P < 0.01). LIMITATIONS: The retrospective nature of this study makes it prone to response and misclassification bias. CONCLUSIONS: BMI and age may be risk factors for persistent postoperative pain after breast cancer treatment. KEY WORDS: Persistent postsurgical pain, breast cancer treatment, BMI, age, chronic postoperative pain, breast cancer surgery.

1H-NMR metabolic profiling of cerebrospinal fluid in patients with complex regional pain syndrome-related dystonia.

In complex regional pain syndrome (CRPS)-related dystonia, compelling evidence points to the involvement of the central nervous system, but the underpinning pathobiology is still unclear. Thus, to enable a hypothesis-free, unbiased view of the problem and to obtain new insight into the pathobiology of dystonia in CRPS, we applied an exploratory metabolomics analysis of cerebrospinal fluid (CSF) of patients with CRPS-related dystonia. (1)H-NMR spectroscopy in combination with multivariate modeling were used to investigate metabolic profiles of a total of 105 CSF samples collected from patients with CRPS-related dystonia and controls. We found a significantly different metabolic profile of CSF in CRPS patients compared to controls. The differences were already reflected in the first two principal components of the principal component analysis model, which is an indication that the variance associated with CRPS is stronger than variance caused by such classical confounders as gender, age, or individual differences. A supervised analysis generated a strong model pinpointing the most important metabolites contributed to the metabolic signature of patients with CRPS-related dystonia. From the set of identified discriminators, the most relevant metabolites were 2-keto-isovalerate, glucose, glutamine, and lactate, which all showed increased concentrations, and urea, which showed decreased concentration in CRPS subjects. Our findings point at a catabolic state in chronic CRPS patients with dystonia that is likely associated with inflammation.