Responsiveness of multiple patient-reported outcome measures for acute postsurgical pain: primary results from the international multi-centre PROMPT NIT-1 study.

BACKGROUND: Postsurgical outcome measures are crucial to define the efficacy of perioperative pain management; however, it is unclear which are most appropriate. We conducted a prospective study aiming to assess sensitivity-to-change of patient-reported outcome measures assessing the core outcome set of domains pain intensity (at rest/during activity), physical function, adverse events, and self-efficacy. METHODS: Patient-reported outcome measures were assessed preoperatively, on day 1 (d1), d3, and d7 after four surgical procedures (total knee replacement, breast surgery, endometriosis-related surgery, and sternotomy). Primary outcomes were sensitivity-to-change of patient-reported outcome measures analysed by correlating their changes (d1-d3) with patients' global impression of change and patients' specific impression of change items as anchor criteria. Secondary outcomes included identification of baseline and patient characteristic variables explaining variance in change for each of the scales and descriptive analysis of various patient-reported outcome measures from different domains and after different surgeries. RESULTS: Of 3322 patients included (18 hospitals, 10 countries), data from 2661 patients were analysed. All patient-reported outcome measures improved on average over time; the median calculated sensitivity-to-change for all patient-reported outcome measures (overall surgeries) was 0.22 (range: 0.07-0.31, scale: 0-10); all changes were independent of baseline data or patient characteristics and similar between different procedures. CONCLUSIONS: Pain-related patient-reported outcome measures have low to moderate sensitivity-to-change; those showing higher sensitivity-to-change from the same domain should be considered for inclusion in a core outcome set of patient-reported outcome measures to assess the effectiveness and efficacy of perioperative pain management.

Regional anaesthesia for postoperative pain management following laparoscopic, visceral, non-oncological surgery a systematic review and meta-analysis.

BACKGROUND: Postoperative pain management following laparoscopic, non-oncological visceral surgery in adults is challenging. Regional anaesthesia could be a promising component in multimodal pain management. METHODS: We performed a systematic review and meta-analysis with GRADE assessment. Primary outcomes were postoperative acute pain intensity at rest/during movement after 24 h, the number of patients with block-related adverse events and the number of patients with postoperative paralytic ileus. RESULTS: 82 trials were included. Peripheral regional anaesthesia combined with general anaesthesia versus general anaesthesia may result in a slight reduction of pain intensity at rest at 24 h (mean difference (MD) - 0.72 points; 95% confidence interval (CI) - 0.91 to - 0.54; I2 = 97%; low-certainty evidence), which was not clinically relevant. The evidence is very uncertain regarding the effect on pain intensity during activity at 24 h (MD -0.8 points; 95%CI - 1.17 to - 0.42; I2 = 99%; very low-certainty evidence) and on the incidence of block-related adverse events. In contrast, neuraxial regional analgesia combined with general anaesthesia (versus general anaesthesia) may reduce postoperative pain intensity at rest in a clinical relevant matter (MD - 1.19 points; 95%CI - 1.99 to - 0.39; I2 = 97%; low-certainty evidence), but the effect is uncertain during activity (MD - 1.13 points; 95%CI - 2.31 to 0.06; I2 = 95%; very low-certainty evidence). There is uncertain evidence, that neuraxial regional analgesia combined with general anaesthesia (versus general anaesthesia) increases the risk for block-related adverse events (relative risk (RR) 5.11; 95%CI 1.13 to 23.03; I2 = 0%; very low-certainty evidence). CONCLUSION: This meta-analysis confirms that regional anaesthesia might be an important part of multimodal postoperative analgesia in laparoscopic visceral surgery, e.g. in patients at risk for severe postoperative pain, and with large differences between surgical procedures and settings. Further research is required to evaluate the use of adjuvants and the additional benefit of regional anaesthesia in ERAS programmes. PROTOCOL REGISTRATION: PROSPERO CRD42021258281.

Perioperative pain management for appendicectomy: A systematic review and Procedure-specific Postoperative Pain Management recommendations.

BACKGROUND: Despite being a commonly performed surgical procedure, pain management for appendicectomy is often neglected because of insufficient evidence on the most effective treatment options. OBJECTIVE: To provide evidence-based recommendations by assessing the available literature for optimal pain management after appendicectomy. DESIGN AND DATA SOURCES: This systematic review-based guideline was conducted according to the PROSPECT methodology. Relevant randomised controlled trials, systematic reviews and meta-analyses in the English language from January 1999 to October 2022 were retrieved from MEDLINE, Embase and Cochrane Databases using PRISMA search protocols. ELIGIBILITY CRITERIA: We included studies on adults and children. If articles reported combined data from different surgeries, they had to include specific information about appendicectomies. Studies needed to measure pain intensity using a visual analogue scale (VAS) or a numerical rating scale (NRS). Studies that did not report the precise appendicectomy technique were excluded. RESULTS: Out of 1388 studies, 94 met the inclusion criteria. Based on evidence and consensus, the PROSPECT members agreed that basic analgesics [paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs)] should be administered perioperatively for open and laparoscopic appendicectomies. A laparoscopic approach is preferred because of lower pain scores. Additional recommendations for laparoscopic appendicectomies include a three-port laparoscopic approach and the instillation of intraperitoneal local anaesthetic. For open appendicectomy, a preoperative unilateral transverse abdominis plane (TAP) block is recommended. If not possible, preincisional infiltration with local anaesthetics is an alternative. Opioids should only be used as rescue analgesia. Limited evidence exists for TAP block in laparoscopic appendicectomy, analgesic adjuvants for TAP block, continuous wound infiltration after open appendicectomy and preoperative ketamine and dexamethasone. Recommendations apply to children and adults. CONCLUSION: This review identified an optimal analgesic regimen for open and laparoscopic appendicectomy. Further randomised controlled trials should evaluate the use of regional analgesia and wound infiltrations with adequate baseline analgesia, especially during the recommended conventional three-port approach. REGISTRATION: The protocol for this study was registered with the PROSPERO database (Registration No. CRD42023387994).

Chronic postsurgical pain: A European survey.

BACKGROUND: Chronic postsurgical pain (CPSP) is a clinical problem, and large prospective studies are needed to determine its incidence, characteristics, and risk factors. OBJECTIVE: To find predictive factors for CPSP in an international survey. DESIGN: Observational study. SETTING: Multicentre European prospective observational trial. PATIENTS: Patients undergoing breast cancer surgery, sternotomy, endometriosis surgery, or total knee arthroplasty (TKA). METHOD: Standardised questionnaires were completed by the patients at 1, 3, and 7 days, and at 1, 3, and 6 months after surgery, with follow-up via E-mail, telephone, or interview. MAIN OUTCOME MEASURE: The primary goal of NIT-1 was to propose a scoring system to predict those patient likely to have CPSP at 6 months after surgery. RESULTS: A total of 3297 patients were included from 18 hospitals across Europe and 2494 patients were followed-up for 6 months. The mean incidence of CPSP at 6 months was 10.5%, with variations depending on the type of surgery: sternotomy 6.9%, breast surgery 7.4%, TKA 12.9%, endometriosis 16.2%. At 6 months, neuropathic characteristics were frequent for all types of surgery: sternotomy 33.3%, breast surgery 67.6%, TKA 42.4%, endometriosis 41.4%. One-third of patients experienced CPSP at both 3 and 6 months. Pre-operative pain was frequent for TKA (leg pain) and endometriosis (abdomen) and its frequency and intensity were reduced after surgery. Severe CPSP and a neuropathic pain component decreased psychological and functional wellbeing as well as quality of life. No overarching CPSP risk factors were identified. CONCLUSION: Unfortunately, our findings do not offer a new CPSP predictive score. However, we present reliable new data on the incidence, characteristics, and consequences of CPSP from a large European survey. Interesting new data on the time course of CPSP, its neuropathic pain component, and CPSP after endometriosis surgery generate new hypotheses but need to be confirmed by further research. TRIAL REGISTRATION: clinicaltrials.gov ID: NCT03834922.

Perioperative pain management models in four European countries: A narrative review of differences, similarities and future directions.

There is general agreement that acute pain management is an important component of perioperative medicine. However, there is no consensus on the best model of care for perioperative pain management, mainly because evidence is missing in many aspects. Comparing the similarities and differences between countries might reveal some insights into different organisational models and how they work. Here, we performed a narrative review to describe and compare the structures, processes and outcomes of perioperative pain management in the healthcare systems of four European countries using Donabedian's framework as a guide. Our comparison revealed many similarities, differences and gaps. Different structures of acute pain services in the four countries with no common definition and standards of care were found. Protocols have been implemented in all countries and guidelines in some. If outcome is assessed, it is mainly pain intensity, and many patients experiencing more intense pain than others have common risk factors (e.g. preoperative pain, preoperative opioid intake, female sex and young age). Outcome assessment beyond pain intensity (such as pain-related physical function, which is important for early rehabilitation and recovery) is currently not well implemented. Developing common quality indicators, a European guideline for perioperative pain management (e.g. for patients at high risk for experiencing severe pain and other outcome parameters) and common criteria for acute pain services might pave the way forward for improving acute pain management in Europe. Finally, the education of general and specialist staff should be aligned in Europe, for example, by using the curricula of the European Pain Federation (EFIC).

Phenotype- and species-specific skin proteomic signatures for incision-induced pain in humans and mice.

BACKGROUND: Acute pain after surgery is common and often leads to chronic post-surgical pain, but neither treatment nor prevention is currently sufficient. We hypothesised that specific protein networks (protein-protein interactions) are relevant for pain after surgery in humans and mice. METHODS: Standardised surgical incisions were performed in male human volunteers and male mice. Quantitative and qualitative sensory phenotyping were combined with unbiased quantitative mass spectrometry-based proteomics and protein network theory. The primary outcomes were skin protein signature changes in humans and phenotype-specific protein-protein interaction analysis 24 h after incision. Secondary outcomes were interspecies comparison of protein regulation as well as protein-protein interactions after incision and validation of selected proteins in human skin by immunofluorescence. RESULTS: Skin biopsies in 21 human volunteers revealed 119/1569 regulated proteins 24 h after incision. Protein-protein interaction analysis delineated remarkable differences between subjects with small (low responders, n=12) and large incision-related hyperalgesic areas (high responders, n=7), a phenotype most predictive of developing chronic post-surgical pain. Whereas low responders predominantly showed an anti-inflammatory protein signature, high responders exhibited signatures associated with a distinct proteolytic environment and persistent inflammation. Compared to humans, skin biopsies in mice habored even more regulated proteins (435/1871) 24 h after incision with limited overlap between species as assessed by proteome dynamics and PPI. Immunohistochemistry confirmed the expression of high priority candidates in human skin biopsies. CONCLUSIONS: Proteome profiling of human skin after incision revealed protein-protein interactions correlated with pain and hyperalgesia, which may be of potential significance for preventing chronic post-surgical pain. Importantly, protein-protein interactions were differentially modulated in mice compared to humans opening new avenues for successful translational research.

Prognostic models for chronic postsurgical pain-Current developments, trends, and challenges.

PURPOSE OF REVIEW: Prognostic models for chronic postsurgical pain (CPSP) aim to predict the likelihood for development and severity of CPSP in individual patients undergoing surgical procedures. Such models might provide valuable information for healthcare providers, allowing them to identify patients at higher risk and implement targeted interventions to prevent or manage CPSP effectively. This review discusses the latest developments of prognostic models for CPSP, their challenges, limitations, and future directions. RECENT FINDINGS: Numerous studies have been conducted aiming to develop prognostic models for CPSP using various perioperative factors. These include patient-related factors like demographic variables, preexisting pain conditions, psychosocial aspects, procedure-specific characteristics, perioperative analgesic strategies, postoperative complications and, as indicated most recently, biomarkers. Model generation, however, varies and performance and accuracy differ between prognostic models for several reasons and validation of models is rather scarce. SUMMARY: Precise methodology of prognostic model development needs advancements in the field of CPSP. Development of more accurate, validated and refined models in large-scale cohorts is needed to improve reliability and applicability in clinical practice and validation studies are necessary to further refine and improve the performance of prognostic models for CPSP.

Combined resting state-fMRI and calcium recordings show stable brain states for task-induced fMRI in mice under combined ISO/MED anesthesia.

For fMRI in animal models, the combination of low-dose anesthetic, isoflurane (ISO), and the sedative medetomidine (MED) has recently become an advocated regimen to achieve stable neuronal states and brain networks in rats that are required for reliable task-induced BOLD fMRI. However, in mice the temporal stability of neuronal states and networks in resting-state (rs)-fMRI experiments during the combined ISO/MED regimen has not been systematically investigated. Using a multimodal approach with optical calcium (Ca2+) recordings and rs-fMRI, we investigated cortical neuronal/astrocytic Ca2+activity states and brain networks at multiple time points while switching from anesthesia with 1% ISO to a combined ISO/MED regimen. We found that cortical activity states reached a steady-state 45 min following start of MED infusion as indicated by stable Ca2+ transients. Similarly, rs-networks were not statistically different between anesthesia with ISO and the combined ISO/MED regimen 45 and 100 min after start of MED. Importantly, during the transition time we identified changed rs-network signatures that likely reflect the different mode of action of the respective anesthetic; these included a dose-dependent increase in cortico-cortical functional connectivity (FC) presumably caused by reduction of ISO concentration and decreased FC in subcortical arousal nuclei due to MED infusion. Furthermore, we report detection of visual stimulation-induced BOLD fMRI during the stable ISO/MED neuronal state 45 min after induction. Based on our findings, we recommend a 45-minute waiting period after switching from ISO anesthesia to the combined ISO/MED regimen before performing rs- or task-induced fMRI experiments.

Incidence, Time Course and Influence on Quality of Life of Intensive Care Unit-Acquired Weakness Symptoms in Long-Term Intensive Care Survivors.

PURPOSE: Intensive care unit-acquired weakness (ICUAW) can manifest as muscle weakness or neuropathy-like symptoms, with diagnosis remaining a challenge. Uncertainties surround the long-term cause and sequelae. Therefore, the purpose was to assess incidence, time course and long-term influence on quality of life (QoL) of symptoms in ICU survivors. METHODS: After ethical approval and registration (www.drks.de: DRKS00011593), in a single-center cohort study all patients admitted to the ICU in 2007-2017 in a German university hospital were screened. Out of 1,860 patients (≥7d ICU care including ventilation support for ≥72 h, at least 6mo-10y after ICU) 636 were deceased, 912 survivors were contacted. RESULTS: 149 former patients (age: 63.5 ± 13.1y; males: 73%; duration in ICU: 20.8 ± 15.7d; duration of ventilation: 16.5 ± 13.7 h; time post-ICU: 4.4 ± 2.7y, 5-10y: 43%) consented to be interviewed concerning occurrence, duration, recovery and consequences of ICUAW-associated muscle weakness or neuropathy-like symptoms after ICU. In 75% at least 1 persistent or previous symmetrical symptom was reported (myopathy-like muscle weakness: 43%; neuropathy-like symptoms: 13%; both: 44%) and rated as incidence of ICUAW. However, only 18% of participants had received an ICUAW diagnosis by their physicians, although 62% had persistent symptoms up to 10y after ICU (5-10y: 46%). Only 37% of participants reported a complete recovery of symptoms, significantly associated with an initially low number of symptoms after ICU (p < 0.0001), myopathy-like symptoms (p = 0.024), and younger age at the time of ICU admission (55.7 ± 13.1 vs. 62.6 ± 10.6y, p < 0.001). ICUAW still impaired the QoL at the time of the interview in 74% of affected survivors, with 30% reporting severe impairment. CONCLUSION: ICUAW symptoms were disturbingly common in the majority of long-term survivors, indicating that symptoms persist up to 10y and frequently impair QoL. However, only a small number of patients had been diagnosed with ICUAW. Trial registry: Deutsches Register Klinischer Studien (DRKS), https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011593, registration number: DRKS00011593.

Pectoral nerve blocks for breast surgery: A meta-analysis.

BACKGROUND: Pectoral nerve blocks (PECS block) might be an interesting new regional anaesthetic technique in patients undergoing breast surgery. OBJECTIVE: The aim of this meta-analysis was to investigate postoperative pain outcomes and adverse events of a PECS block compared with no treatment, sham treatment or other regional anaesthetic techniques in women undergoing breast surgery. DESIGN: We performed a systematic review of randomised controlled trials (RCT) with meta-analysis and risk of bias assessment. DATA SOURCES: The databases MEDLINE, CENTRAL (until December 2019) and clinicaltrials.gov were systematically searched. ELIGIBILITY CRITERIA: All RCTs investigating the efficacy and adverse events of PECS compared with sham treatment, no treatment or other regional anaesthetic techniques in women undergoing breast surgery with general anaesthesia were included. RESULTS: A total of 24 RCTs (1565 patients) were included. PECS (compared with no treatment) block might reduce pain at rest [mean difference -1.14, 95% confidence interval (CI), -2.1 to -0.18, moderate quality evidence] but we are uncertain regarding the effect on pain during movement at 24 h after surgery (mean difference -1.79, 95% CI, -3.5 to -0.08, very low-quality evidence). We are also uncertain about the effect of PECS block on pain at rest at 24 h compared with sham block (mean difference -0.83, 95% CI, -1.80 to 0.14) or compared with paravertebral block (PVB) (mean difference -0.18, 95% CI, -1.0 to 0.65), both with very low-quality evidence. PECS block may have no effect on pain on movement at 24 h after surgery compared with PVB block (mean difference -0.56, 95% CI, -1.53 to 0.41, low-quality evidence). Block-related complications were generally poorly reported. CONCLUSION: There is moderate quality evidence that PECS block compared with no treatment reduces postoperative pain intensity at rest. The observed results were less pronounced if patients received a sham block. Furthermore, PECS blocks might be equally effective as PVBs. Due to mostly low-quality or very low-quality evidence level, further research is warranted. PROTOCOL REGISTRATION: CRD42019126733.

[Procedure Specific Pain Therapy - the PROSPECT Idea]. / Prozedurenspezifische Schmerztherapie ­ der PROSPECT-Ansatz.

Acute pain therapy following operative or interventional procedures has become a compulsory component of a modern perioperative patient management. A structured pain regimen has several clear advantages: it leads to an improvement of the patients' quality of life in the short term, it reduces perioperative morbidity in the medium term, it reduces pain chronification in the long term, at the same time improving the economic efficiency due to an accelerated mobilization, a reduction of the hospitalization and an avoidance of complication inherent costs.This article provides detailed information on the change of paradigm, away from a generalized and rather unspecific acute pain therapy towards a problem oriented procedure specific regimen. It points out two examples of the PROSPECT (PROcedure SPECific pain managemenT) methodology and explains its background.

Efficacy and safety of dexmedetomidine in peripheral nerve blocks: A meta-analysis and trial sequential analysis.

BACKGROUND: The duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, several additives, including dexmedetomidine (DEX), have been investigated in order to prolong postoperative analgesia following single-shot regional anaesthesia. OBJECTIVES: The aim of this meta-analysis was to assess the efficacy and safety of the addition of perineural DEX to local anaesthetics compared with local anaesthetics alone or local anaesthetics combined with systemic administration of DEX. DESIGN: A systematic review of randomised controlled trials (RCT) with meta-analysis, trial sequential analysis and assessment of the quality of evidence by the GRADE approach. DATA SOURCES: The databases MEDLINE, CENTRAL and EMBASE (to May 2017) were systematically searched. ELIGIBILITY CRITERIA: All RCTs investigating the efficacy and safety of perineural DEX combined with local anaesthetics compared with local anaesthetics alone or local anaesthetics in combination with systemic DEX in peripheral nerve blocks of adults undergoing surgery were included. RESULTS: A total of 46 RCTs (3149 patients) were included. Patients receiving perineural DEX combined with local anaesthetics had a longer duration of analgesia than local anaesthetics alone [mean difference 4.87 h; 95% confidence interval (95% CI) 4.02 to 5.73; P < 0.001; I = 100%; moderate-quality evidence]. The most important adverse events in the DEX group were intraoperative bradycardia [risk ratio 2.83; 95% CI 1.50 to 5.33; P = 0.035; I = 40%; very low-quality evidence] and hypotension (risk ratio 3.42; 95% CI 1.24 to 9.48; P = 0.002; I = 65%; very low quality evidence). In contrast, there were no differences in the duration of analgesia between perineural or intravenous DEX combined with local anaesthetics (mean difference 0.98 h; 95% CI -0.12 to 2.08; P = 0.08; I = 0%). CONCLUSION: This meta-analysis demonstrated that DEX in combination with local anaesthetics increases postoperative analgesia for around 5 h. However, there are higher risks of intraoperative hypotension and bradycardia. Findings on side effects are associated with high uncertainty. Initial evidence suggests no difference in the duration of analgesia associated with systemic or perineural DEX. TRIAL REGISTRATION: CRD42016042486.

Efficacy and safety of buprenorphine in peripheral nerve blocks: A meta-analysis of randomised controlled trials.

BACKGROUND: The duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, a variety of additives to local anaesthetics have been investigated to prolong postoperative analgesia following single-shot nerve blocks. OBJECTIVE(S): The aims of the current meta-analysis were to assess the efficacy and safety of the addition of perineural buprenorphine to local anaesthetic compared with local anaesthetic alone, or combined with systemic administration of buprenorphine, or other perineural opioids for peripheral nerve blocks. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: The following data sources were systematically searched: MEDLINE, CENTRAL and EMBASE (till 03/2016). ELIGIBILITY CRITERIA: All RCTs focusing on the efficacy and safety of perineural buprenorphine combined with local anaesthetic compared with local anaesthetic alone, or in combination with systemic buprenorphine, or other perineural opioids for peripheral nerve blocks were included. RESULTS: We included 13 RCTs (685 patients). Participants treated with perineural buprenorphine combined with local anaesthetic showed a longer duration of analgesia compared with those receiving local anaesthetic alone [mean difference 8.64 h, 95% confidence interval (CI) (6.44 to 10.85); P < 0.01]. However, the buprenorphine group had a significantly higher relative risk (RR) for postoperative nausea and vomiting (PONV) [RR 5.0, 95% CI (1.12 to 22.27); P = 0.03]. The perineural administration of buprenorphine provided a longer duration of analgesia than an intramuscular application [mean difference 6.87 h, 95% CI (4.02 to 9.71); P < 0.01] without evidence of a difference in the incidence of PONV between the modes of administration [RR 0.76, 95% CI (0.28 to 2.03); P = 0.58]. CONCLUSION: This meta-analysis revealed that the addition of buprenorphine to a local anaesthetic peripheral nerve block prolongs postoperative analgesia for about 8 h but significantly increases the risk for PONV. Perineural administration is more effective than systemic application but is associated with a similar risk of PONV. However, these results were influenced by heterogeneity so that further trials (especially head-to-head comparisons) are needed in the future. TRIAL REGISTRATION: PROSPERO(www.crd.york.ac.uk) identifier: CRD42016036054.

Short-term test-retest-reliability of conditioned pain modulation using the cold-heat-pain method in healthy subjects and its correlation to parameters of standardized quantitative sensory testing.

BACKGROUND: Conditioned Pain Modulation (CPM) is often used to assess human descending pain inhibition. Nine different studies on the test-retest-reliability of different CPM paradigms have been published, but none of them has investigated the commonly used heat-cold-pain method. The results vary widely and therefore, reliability measures cannot be extrapolated from one CPM paradigm to another. Aim of the present study was to analyse the test-retest-reliability of the common heat-cold-pain method and its correlation to pain thresholds. METHODS: We tested the short-term test-retest-reliability within 40 ± 19.9 h using a cold-water immersion (10 °C, left hand) as conditioning stimulus (CS) and heat pain (43-49 °C, pain intensity 60 ± 5 on the 101-point numeric rating scale, right forearm) as test stimulus (TS) in 25 healthy right-handed subjects (12females, 31.6 ± 14.1 years). The TS was applied 30s before (TSbefore), during (TSduring) and after (TSafter) the 60s CS. The difference between the pain ratings for TSbefore and TSduring represents the early CPM-effect, between TSbefore and TSafter the late CPM-effect. Quantitative sensory testing (QST, DFNS protocol) was performed on both sessions before the CPM assessment. STATISTICS: paired t-tests, Intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Pearson's correlation, Bland-Altman analysis, significance level p < 0.05 with Bonferroni correction for multiple comparisons, when necessary. RESULTS: Pain ratings during CPM correlated significantly (ICC: 0.411…0.962) between both days, though ratings for TSafter were lower on day 2 (p < 0.005). The early (day 1: 16.7 ± 11.7; day 2: 19.5 ± 11.9; ICC: 0.618, SRD: 20.2) and late (day 1: 1.7 ± 9.2; day 2: 7.6 ± 11.5; ICC: 0.178, SRD: 27.0) CPM effect did not differ significantly between both days. Both early and late CPM-effects did not correlate with the pain thresholds. CONCLUSIONS: The short-term test-retest-reliability of the early CPM-effect using the heat-cold-pain method in healthy subjects achieved satisfying results in terms of the ICC. The SRD of the early CPM effect showed that an individual change of > 20 NRS can be attributed to a real change rather than chance. The late CPM-effect was weaker and not reliable.

Monitoring heart rate variability to assess experimentally induced pain using the analgesia nociception index: A randomised volunteer study.

BACKGROUND: Pain assessment using a numerical rating scale (NRS) is considered good clinical practice, but objective assessment in noncommunicating patients is still a challenge. A potential solution is to monitor changes in heart rate variability transformed into the analgesia nociception index (ANI), that offers a noninvasive means of pain quantification. OBJECTIVES: The aim was to measure magnitudes, descending slopes and time courses of ANI following expected and unexpected painful, nonpainful and sham experimental stimuli and compare these with pain intensity as assessed by NRS in conscious human volunteers. We expected a negative correlation between ANI and NRS after painful stimuli. DESIGN: Randomised stimuli and placebo-controlled, single-blinded study. SETTING: Experimental pain simulation laboratory, Bochum, Germany. PARTICIPANTS: Twenty healthy male students, (mean ±â€Šstandard deviation; 24.2 ±â€Š1.9 years) recruited via local advertising, were consecutively included. INTERVENTION: ANI values were continuously recorded. After resting, four stimuli were applied in a random order on the right forearm (unexpected and expected electrical pain, expected nonpainful and sham stimuli). Blinded volunteers were asked to rate all four stimuli on NRS. MAIN OUTCOME MEASURES: ANI means (0-100), amplitudes, maxima, minima and slopes with NRS pain intensity scores (0-10). RESULTS: Resting alert volunteers showed ANI values of 82.05 ±â€Š10.71. ANI decreased after a random stimulus (maximal decrease of 25.0 ±â€Š7.3%), but different kinds of stimuli evoked similar results. NRS scores (median; interquartiles) were significantly (P = 0.008) higher after expected (5.25; 3.5-6.75) compared with unexpected (4.50; 3.0-5.0) pain stimuli. No correlation was found between ANI and NRS. CONCLUSION: ANI did not allow a differentiation of painful, nonpainful or sham stimuli in alert volunteers. Therefore, ANI does not exclusively detect nociception, but may be modified by stress and emotion. Thus, we conclude that ANI is not a specific, robust measure for assessment of pain intensity.

Age- and procedure-specific differences of epidural analgesia in children--a database analysis.

OBJECTIVE: Several audits demonstrated the safety of epidural catheters in children undergoing surgery. Within the present data analysis, we investigated whether older compared with younger children and children with specific types of surgical procedures might report higher pain scores. METHODS: All children (0-18 years) treated with an epidural catheter for postoperative pain treatment between March 2006 and December 2010 at the University Hospital of Muenster (Germany) were included. Postoperative pain intensities, the number of patients with the need for additional opioids, and catheter-related complications during placement and early postoperative period were analyzed. RESULTS: Data of 830 children receiving an epidural catheter (Nthoracic/lumbar = 691; Ncaudal = 139) were included. Adolescents (12-18 years) treated with a thoracic/lumbar epidural had higher pain scores compared with preschoolers and school children (P < 0.05) and received less additional systemic opioids (P < 0.001). In the thoracic/lumbar epidural group, children undergoing spine surgery showed comparable pain scores with those undergoing thoracic procedures, but had higher pain scores than children undergoing abdominal or extremity surgery (P < 0.05). However, children undergoing spine surgery received less additional opioids, but this was only significant at the first postoperative day (P = 0.032). CONCLUSIONS: This database analysis demonstrated that older children and children undergoing thoracic or spine surgery reported significant higher pain scores most likely because they received less additional opioids. Therefore, a more "aggressive" pain treatment (including opioids on demand under appropriate monitoring) might further improve postoperative care.

Regional analgesia techniques for total knee replacement.

PURPOSE OF REVIEW: Pain following total knee arthroplasty is a challenging task for healthcare providers. Concurrently, fast recovery and early ambulation are required to regain function and to prevent postoperative complications. Ideal postoperative analgesia provides sufficient pain relief with minimal opioid consumption and preservation of motor strength. Regional analgesia techniques are broadly used to answer these expectations. Femoral nerve blocks are performed frequently but have suggested disadvantages, such as motor weakness. The use of lumbar epidurals is questioned because of the risk of epidural hematoma. Relatively new techniques, such as local infiltration analgesia or adductor canal blocks, are increasingly discussed. The present review discusses new findings and weight between known benefits and risks of all of these techniques for total knee arthroplasty. RECENT FINDINGS: Femoral nerve blocks are the gold standard for total knee arthroplasty. The standard use of additional sciatic nerve blocks remains controversial. Lumbar epidurals possess an unfavourable risk/benefit ratio because of increased rate of epidural hematoma in orthopaedic patients and should be reserved for lower limb amputation; peripheral regional techniques provide comparable pain control, greater satisfaction and less risk than epidural analgesia. Although motor weakness might be greater with femoral nerve blocks compared with no regional analgesia, new data point towards a similar risk of falls after total knee arthroplasty with or without peripheral nerve blocks. Local infiltration analgesia and adductor canal blockade are promising recent techniques to gain adequate pain control with a minimum of undesired side-effects. SUMMARY: Femoral nerve blocks are still the gold standard for an effective analgesia approach in knee arthroplasty and should be supplemented (if needed) by oral opioids. An additional sciatic nerve blockade is still controversial and should be an individual decision. Large-scale studies are needed to reinforce the promising results of newer regional techniques, such as local infiltration analgesia and adductor canal block.

Perioperative pain management with regional analgesia techniques for visceral cancer surgery: A systematic review and meta-analysis.

STUDY OBJECTIVE: Regional analgesia following visceral cancer surgery might provide an advantage but evidence for best treatment options related to risk-benefit is unclear. DESIGN: Systematic review of randomized controlled trials (RCT) with meta-analysis and GRADE assessment. SETTING: Postoperative pain treatment. PATIENTS: Adult patients undergoing visceral cancer surgery. INTERVENTIONS: Any kind of peripheral (PRA) or epidural analgesia (EA) with/without systemic analgesia (SA) was compared to SA with or without placebo treatment or any other regional anaesthetic techniques. MEASUREMENTS: Primary outcome measures were postoperative acute pain intensity at rest and during activity 24 h after surgery, the number of patients with block-related adverse events and postoperative paralytic ileus. MAIN RESULTS: 59 RCTs (4345 participants) were included. EA may reduce pain intensity at rest (mean difference (MD) -1.05; 95% confidence interval (CI): -1.35 to -0.75, low certainty evidence) and during activity 24 h after surgery (MD -1.83; 95% CI: -2.34 to -1.33, very low certainty evidence). PRA likely results in little difference in pain intensity at rest (MD -0.75; 95% CI: -1.20 to -0.31, moderate certainty evidence) and pain during activity (MD -0.93; 95% CI: -1.34 to -0.53, moderate certainty evidence) 24 h after surgery compared to SA. There may be no difference in block-related adverse events (very low certainty evidence) and development of paralytic ileus (very low certainty of evidence) between EA, respectively PRA and SA. CONCLUSIONS: Following visceral cancer surgery EA may reduce pain intensity. In contrast, PRA had only limited effects on pain intensity at rest and during activity. However, we are uncertain regarding the effect of both techniques on block-related adverse events and paralytic ileus. Further research is required focusing on regional analgesia techniques especially following laparoscopic visceral cancer surgery.