Thoracic Epidural Analgesia Is Not Associated With Improved Survival After Pancreatic Surgery: Long-Term Follow-Up of the Randomized Controlled PAKMAN Trial.

BACKGROUND: Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are common forms of analgesia after pancreatic surgery. Current guidelines recommend EDA over PCIA, and evidence suggests that EDA may improve long-term survival after surgery, especially in cancer patients. The aim of this study was to determine whether perioperative EDA is associated with an improved patient prognosis compared to PCIA in pancreatic surgery. METHODS: The PAKMAN trial was an adaptive, pragmatic, international, multicenter, randomized controlled superiority trial conducted from June 2015 to October 2017. Three to five years after index surgery a long-term follow-up was performed from October 2020 to April 2021. RESULTS: For long-term follow-up of survival, 109 patients with EDA were compared to 111 patients with PCIA after partial pancreatoduodenectomy (PD). Long-term follow-up of quality of life (QoL) and pain assessment was available for 40 patients with EDA and 45 patients with PCIA (questionnaire response rate: 94%). Survival analysis revealed that EDA, when compared to PCIA, was not associated with improved overall survival (OS, HR, 1.176, 95% HR-CI, 0.809-1.710, P = .397, n = 220). Likewise, recurrence-free survival did not differ between groups (HR, 1.116, 95% HR-CI, 0.817-1.664, P = .397, n = 220). OS subgroup analysis including only patients with malignancies showed no significant difference between EDA and PCIA (HR, 1.369, 95% HR-CI, 0.932-2.011, P = .109, n = 179). Similar long-term effects on QoL and pain severity were observed in both groups (EDA: n = 40, PCIA: n = 45). CONCLUSIONS: Results from this long-term follow-up of the PAKMAN randomized controlled trial do not support favoring EDA over PCIA in pancreatic surgery. Until further evidence is available, EDA and PCIA should be considered similar regarding long-term survival.

[Applicability of QUIKS in conservatively treated tumor inpatients]. / Anwendbarkeit von QUIKS bei stationär konservativ behandelten Tumorpatienten.

BACKGROUND: Quality improvement in conservative pain management (QUIKS), a module for nonoperative patients in the QUIPS project was tested on a cohort of tumor patients regarding its applicability. MATERIAL AND METHODS: Conservatively treated inpatients at the University Hospital of Würzburg (UKW) were prospectively surveyed on the quality of pain management using the QUIKS outcome questionnaire (AZ 129/17, Ethics Committee at UKW). Information on therapy and demographics was taken from the hospital's internal documentation system. RESULTS: During the data collection period 100 conservatively treated inhouse tumor patients from different hospitals were included. Of the patients 74% required assistance in answering the questionnaire. Functional limitations or pain treatment-related side effects were present in 77% of the patients; the average pain level was 6 on the numerical rating scale. The most commonly reported type of pain was back pain and headache. Of the patients 18% received pain therapy with opioids and 26% with nonopioids, adjustment was made in 5% with opioids and in 44% with nonopioids and pain medicine specialists were consulted in 9% of cases. CONCLUSION: The application of the questionnaire was well accepted by the patients but required a high level of assistance in completing it. A high level of pain was observed during the hospital stay and the adjustment of pain therapy or the involvement of pain medicine specialists was rare. The interpretation of statements regarding the quality of tumor pain may be limited as other (pre-existing) pain entities, such as nontumor-associated pain or chronic tumor pain could not be clearly delineated.

[Breakthrough pain in cancer patients]. / Der chronische Schmerzpatient als Notfall. Durchbruchschmerz beim Tumorpatienten.

The treatment of cancer pain shows a special challenge in the ambulatory and stationary treatment of various medical departments. A multifactorial design has to be established for the treatment of breakthrough pain episodes. The development of fast acting lipophilic opioids has improved the therapy of breakthrough pain. Combining these opioids with non-opioid analgetics, adjuvant drugs, interventional procedures, radiotherapy, orthotic devices and surgical /orthopedic interventions delivers a multimodal approach to manage breakthrough cancer pain.

Influencing factors of early cognitive deficits after ambulatory anesthesia.

BACKGROUND: Anesthesia has an influence on early postoperative cognitive function. This is specifically relevant in ambulatory surgery. At discharge, patients must return to their normal life and manage simple tasks. Goal was to detect influencing factors of early postoperative cognitive dysfunction after ambulatory anesthesia. METHODS: With approval of the local ethics committee, 102 individuals scheduled for ambulatory anesthesia were examined with a specific test battery. Cued and uncued reaction time, divided and selective attention were tested prior to anesthesia and at the time of discharge. Differences between the two examinations and potential influencing factors including age, premedication, type and duration of anesthesia were evaluated with the Student t-test and linear regression. P < 0.05 considered significant. RESULTS: In all, 86 individuals completed the study. Both reaction times were reduced after anesthesia compared to before. No differences were seen for divided and selective attention. Age influenced on the post-anesthesia reaction time while all other factors did not. CONCLUSION: Reaction time but not attention as more complex cognitive function is influenced by anesthesia. Age seems to be an important factor in early postoperative cognitive dysfunction.

Gastrointestinal Complications After Pancreatoduodenectomy With Epidural vs Patient-Controlled Intravenous Analgesia: A Randomized Clinical Trial.

Importance: Morbidity is still high in pancreatic surgery, driven mainly by gastrointestinal complications such as pancreatic fistula. Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are frequently used for pain control after pancreatic surgery. Evidence from a post hoc analysis suggests that PCIA is associated with fewer gastrointestinal complications. Objective: To determine whether postoperative PCIA decreases the occurrence of gastrointestinal complications after pancreatic surgery compared with EDA. Design, Setting, and Participants: In this adaptive, pragmatic, international, multicenter, superiority randomized clinical trial conducted from June 30, 2015, to October 1, 2017, 371 patients at 9 European pancreatic surgery centers who were scheduled for elective pancreatoduodenectomy were randomized to receive PCIA (n = 185) or EDA (n = 186); 248 patients (124 in each group) were analyzed. Data were analyzed from February 22 to April 25, 2019, using modified intention to treat and per protocol. Interventions: Patients in the PCIA group received general anesthesia and postoperative PCIA with intravenous opioids with the help of a patient-controlled analgesia device. In the EDA group, patients received general anesthesia and intraoperative and postoperative EDA. Main Outcomes and Measures: The primary end point was a composite of pancreatic fistula, bile leakage, delayed gastric emptying, gastrointestinal bleeding, or postoperative ileus within 30 days after surgery. Secondary end points included 30-day mortality, other complications, postoperative pain levels, intraoperative or postoperative use of vasopressor therapy, and fluid substitution. Results: Among the 248 patients analyzed (147 men; mean [SD] age, 64.9 [10.7] years), the primary composite end point did not differ between the PCIA group (61 [49.2%]) and EDA group (57 [46.0%]) (odds ratio, 1.17; 95% CI, 0.71-1.95 P = .54). Neither individual components of the primary end point nor 30-day mortality, postoperative pain levels, or intraoperative and postoperative substitution of fluids differed significantly between groups. Patients receiving EDA gained more weight by postoperative day 4 than patients receiving PCIA (mean [SD], 4.6 [3.8] vs 3.4 [3.6] kg; P = .03) and received more vasopressors (46 [37.1%] vs 31 [25.0%]; P = .04). Failure of EDA occurred in 23 patients (18.5%). Conclusions and Relevance: This study found that the choice between PCIA and EDA for pain control after pancreatic surgery should not be based on concerns regarding gastrointestinal complications because the 2 procedures are comparable with regard to effectiveness and safety. However, EDA was associated with several shortcomings. Trial Registration: German Clinical Trials Register: DRKS00007784.

What is normal trauma healing and what is complex regional pain syndrome I? An analysis of clinical and experimental biomarkers.

Complex regional pain syndrome (CRPS) typically develops after fracture or trauma. Many of the studies so far have analyzed clinical and molecular markers of CRPS in comparison with healthy or pain controls. This approach, however, neglects mechanisms occurring during physiological trauma recovery. Therefore, we compared the clinical phenotype, sensory profiles, patient-reported outcomes, and exosomal immunobarrier microRNAs (miRs) regulating barrier function and immune response between CRPS and fracture controls (FCs) not fulfilling the CRPS diagnostic criteria. We included upper-extremity FCs, acute CRPS I patients within 1 year after trauma, a second disease control group (painful diabetic polyneuropathy), and healthy controls. Fracture controls were not symptoms-free, but reported some pain, disability, anxiety, and cold pain hyperalgesia in quantitative sensory testing. Patients with CRPS had higher scores for pain, disability, and all patient-reported outcomes. In quantitative sensory testing, ipsilateral and contralateral sides differed significantly. However, on the affected side, patients with CRPS were more sensitive in only 3 parameters (pinprick pain and blunt pressure) when compared to FCs. Two principal components were identified in the cohort: pain and psychological parameters distinguishing FC and CPRS. Furthermore, the immunobarrier-protective hsa-miR-223-5p was increased in plasma exosomes in FCs with normal healing, but not in CRPS and healthy controls. Low hsa-miR-223-5p was particularly observed in subjects with edema pointing towards barrier breakdown. In summary, normal trauma healing includes some CRPS signs and symptoms. It is the combination of different factors that distinguish CRPS and FC. Fracture control as a control group can assist to discover resolution factors after trauma.