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Study objective Evidence for red blood cell (RBC) transfusion thresholds in the intraoperative setting is limited, and current perioperative recommendations may not correspond with individual intraoperative physiological demands. Hemodynamics relevant for the decision to transfuse may include peripheral perfusion index (PPI). The objective of this prospective study was to assess the associations of PPI and hemoglobin levels with the risk of postoperative morbidity and mortality. Design Multicenter cohort study. Setting Bispebjerg and Hvidovre University Hospitals, Copenhagen, Denmark. Patients We included 741 patients who underwent acute high risk abdominal surgery or hip fracture surgery. Interventions No interventions were carried out. Measurements Principal values collected included measurements of peripheral perfusion index and hemoglobin values. Methods The study was conducted using prospectively obtained data on adults who underwent emergency high-risk surgery. Subjects were categorized into high vs. low subgroups stratified by pre-defined PPI levels (PPI: > 1.5 vs. < 1.5) and Hb levels (Hb: > 9.7 g/dL vs. < 9.7 g/dL). The study assessed mortality and severe postoperative complications within 90 days. Main results We included 741 patients. 90-day mortality was 21% (n = 154), frequency of severe postoperative complications was 31% (n = 231). Patients with both low PPI and low Hb had the highest adjusted odds ratio for both 90-day severe postoperative complications (2.95, [1.62–5.45]) and 90-day mortality (3.13, [1.45–7.11]). A comparison of patients with low PPI and low Hb to those with high PPI and low Hb detected significantly higher 90-day mortality risk in the low PPI and low Hb group (OR 8.6, [1.57–162.10]). Conclusion High PPI in acute surgical patients who also presents with anemia was associated with a significantly b, Study objective: Evidence for red blood cell (RBC) transfusion thresholds in the intraoperative setting is limited, and current perioperative recommendations may not correspond with individual intraoperative physiological demands. Hemodynamics relevant for the decision to transfuse may include peripheral perfusion index (PPI). The objective of this prospective study was to assess the associations of PPI and hemoglobin levels with the risk of postoperative morbidity and mortality. Design: Multicenter cohort study. Setting: Bispebjerg and Hvidovre University Hospitals, Copenhagen, Denmark. Patients: We included 741 patients who underwent acute high risk abdominal surgery or hip fracture surgery. Interventions: No interventions were carried out. Measurements: Principal values collected included measurements of peripheral perfusion index and hemoglobin values. Methods: The study was conducted using prospectively obtained data on adults who underwent emergency high-risk surgery. Subjects were categorized into high vs. low subgroups stratified by pre-defined PPI levels (PPI: > 1.5 vs. < 1.5) and Hb levels (Hb: > 9.7 g/dL vs. < 9.7 g/dL). The study assessed mortality and severe postoperative complications within 90 days. Main results: We included 741 patients. 90-day mortality was 21% (n = 154), frequency of severe postoperative complications was 31% (n = 231). Patients with both low PPI and low Hb had the highest adjusted odds ratio for both 90-day severe postoperative complications (2.95, [1.62–5.45]) and 90-day mortality (3.13, [1.45–7.11]). A comparison of patients with low PPI and low Hb to those with high PPI and low Hb detected significantly higher 90-day mortality risk in the low PPI and low Hb group (OR 8.6, [1.57–162.10]). Conclusion: High PPI in acute surgical patients who also presents with anemia was associated with a significantly better outcome when compared with patients with both low PPI and anemia. PPI should therefore be further investigat

Background: Postoperative pain after total knee arthroplasty (TKA) is a continuing problem despite optimised multimodal analgesia. Previous studies have shown preoperative glucocorticoids to reduce postoperative pain, but knowledge about specific doses and effects in specific patient groups is lacking. Methods: A two-centre, double-blind, two-arm study comparing preoperative dexamethasone (1 mg kg−1 vs 0.3 mg kg−1 i.v.) on postoperative pain in 160 planned TKA subjects with low preoperative pain catastrophising and no opioid use. Subjects received multimodal analgesia with paracetamol, cyclooxygenase-2 inhibitors, local anaesthetic infiltration analgesia, and rescue opioids. The primary outcome was percentage of subjects experiencing moderate to severe pain (visual analogue scale >30 mm) upon ambulation at 24 h. Secondary outcomes included pain scores, postoperative inflammation (C-reactive protein), opioid and antiemetics use, and ‘Quality of Recovery-15’ and ‘Opioid-Related Symptom Distress Scale’, length of stay, readmissions, and complications up to Day 90. Results: A total of 157 subjects (80 vs 77) were included. No difference was found between groups in the incidence of subjects experiencing visual analogue scale >30 on ambulation 24 h after surgery (56% vs 53%, relative risk =1.07, confidence interval: 0.8–1.4, P=0.65). No differences in other pain outcomes or use of rescue opioids and antiemetics, in Quality of Recovery-15 and Opioid-Related Symptom Distress Scale, length of stay, readmissions, or complications. C-reactive protein values were comparable at 24 h (13 [6–25] mg L−1 vs 16 [9–38] mg L−1, P = 0.07), but lower at 48 h (26 [9–52] mg L−1 vs 50 [30–72] mg L−1, P<0.01) in the high-dose group. Conclusion: Use of 1 mg kg−1 vs 0.3 mg kg−1 i.v. dexamethasone in low pain responders after TKA did not improve early postoperative pain or other outcomes in contr

Background: Identifying patients at high risk of acute postoperative pain after total knee or hip arthroplasty (TKA/THA) will facilitate individualized pain management and research on the efficacy of treatment options. Numerous studies have reported that psychological patient factors may influence acute postoperative pain, but most reviews have focused on chronic pain and functional outcomes. This systematic review aims to evaluate which psychological metrics are associated with acute postoperative pain after TKA and THA. Methods: A systematic search was conducted using the databases PubMed, EMBASE, Web of Science, and Cochrane Library until June 2022. Full-text articles reporting associations of preoperative psychological factors with acute pain within 48 h of TKA or THA surgery were identified. Quality was assessed using the Quality in Prognostic Studies tool. Results: Eighteen studies containing 16 unique study populations were included. TKA was the most common procedure, and anxiety and depression were the most evaluated psychological metrics. Several different anesthetic techniques and analgesic regimens were used. The studies were generally rated as having a low to moderate risk of bias. Catastrophizing was associated with acute pain in six studies (of nine), mainly after TKA. In contrast, three studies (of 13) and two studies (of 13) found anxiety and depression, respectively, to be associated with acute postoperative pain. Conclusion: Pain catastrophizing seemed to be the most consistent psychological predictor of acute postoperative pain after TKA. The results for other psychological factors and THA were inconsistent. However, the interpretation of results was limited by considerable methodological heterogeneity.

Pain after total knee arthroplasty (TKA) is a well-known clinical problem potentially delaying ambulation and recovery. Perioperative glucocorticoids reduce pain and facilitate early recovery, but the optimal timing and dose are still unknown. High pain catastrophizers have an increased risk of poorly controlled postoperative pain, and moderate to severe pain at 24 h is associated with a risk of pain relapse at 48 h. To evaluate the effect of a repeat moderate dose of glucocorticoids after TKA in high pain catastrophizers presenting with moderate to severe pain 24 h postoperatively, having received preoperative high-dose glucocorticoids. High pain catastrophizers (Pain Catastrophizing Scale > 20) undergoing TKA are screened 24 h postoperatively and are included if they experience moderate to severe pain (VAS > 30) during a 5 m walk test. The included patients will receive either oral 24 mg dexamethasone (n = 55) or placebo (n = 55) on the evening of Day 1 (~30–37 h) after surgery. In addition, patients receive a standard multimodal analgesic regimen, including paracetamol, celecoxib, local infiltration analgesia, and preoperative dexamethasone (1 mg/kg). Patients will fill out a pain diary for 7 days after surgery. The primary outcome is moderate to severe pain (VAS > 30) during a 5 m walk test on the morning of Day 2 after surgery. The secondary outcomes include cumulated pain at rest and during ambulation, cumulated use of rescue analgesics, quality of sleep, lethargy, dizziness, nausea, satisfaction with the analgesic regimen, length of stay, morbidity, mortality, and reasons for readmissions. Follow-up is at 8 and 30 days. The data from this study will provide evidence for the effect of a repeated dose of dexamethasone as an analgesic adjuvant in patients undergoing TKA with a high risk of postoperative pain.

Purpose: Early postoperative mobilization can be hindered by orthostatic intolerance (OI). Postoperative OI has multifactorial pathogenesis, possibly involving both postoperative hypovolemia and autonomic dysfunction. We aimed to investigate the effect of mild acute blood loss from blood donation simulating postoperative hypovolemia, on both autonomic function and OI, thus eliminating confounding perioperative factors such as inflammation, residual anesthesia, pain, and opioids. Methods: This prospective observational cohort study included 26 blood donors. Continuous electrocardiogram data were collected during mobilization and night sleep, both before and after blood donation. A Valsalva maneuver and a standardized mobilization procedure were performed immediately before and after blood donation, during which cardiovascular and tissue oxygenation variables were continuously measured by LiDCOrapid™ and Massimo Root™, respectively. The incidence of OI, hemodynamic responses during mobilization and Valsalva maneuver, as well as heart rate variability (HRV) responses during mobilization and sleep were compared before and 15 min after blood donation. Results: Prior to blood donation, no donors experienced OI during mobilization. After blood donation, 6/26 (23%; 95% CI, 9 to 44) donors experienced at least one OI symptom. Three out of 26 donors (12%; 95% CI, 2 to 30) terminated the mobilization procedure prematurely because of severe OI symptoms. Cardiovascular and cerebral tissue oxygenation responses were reduced in patients with severe OI. After blood loss, HRV indices of total autonomic power remained unchanged but increased sympathetic and decreased parasympathetic outflow was observed during mobilization, but also during sleep, indicating a prolonged autonomic effect of hypovolemia. Conclusion: We describe a specific hypovolemic component of postoperative OI, independent of postoperative autonomic dysfunction, inflammation, opioids, and pain. Study registration

Background: Early postoperative mobilization can be hindered by orthostatic intolerance (OI) due to failed orthostatic cardiovascular regulation. The underlying mechanisms are not fully understood and specific data after total knee arthroplasty (TKA) are lacking. Therefore, we evaluated the incidence of OI and the cardiovascular response to mobilization in fast-track TKA. Methods: This prospective observational cohort study included 45 patients scheduled for primary TKA in spinal anesthesia with a multimodal opioid-sparing analgesic regime. OI and the cardiovascular response to sitting and standing were evaluated with a standardized mobilization procedure preoperatively, and at 6 and 24 h postoperatively. Hemodynamic variables were measured non-invasively (LiDCO™ Rapid). Perioperative bleeding, fluid balance, surgery duration, postoperative hemoglobin, opioid use, and pain during mobilization were recorded. Results: Eighteen (44%) and 8 (22%) patients demonstrated OI at 6 and 24 h after surgery, respectively. Four (10%) and 2 (5%) patients experienced severe OI and terminated the mobilization procedure prematurely. Dizziness was the most common OI symptom during mobilization at 6 h. OI was associated with decreased orthostatic responses in systolic, diastolic, mean arterial pressures, and heart rate (all p <.05), while severe OI patients demonstrated impaired diastolic, mean arterial pressures, heart rate, and cardiac output responses (all p <.05). No statistically significant differences in perioperative bleeding, fluid balance, surgery duration, postoperative hemoglobin, pain, or opioid use were observed between orthostatic tolerant and intolerant patients. Conclusion: Early postoperative OI is common following fast-track TKA. Pathophysiologic mechanisms include impaired orthostatic cardiovascular responses. The progression to severe OI symptoms appears to be primarily due to inadequate heart rate response.

Background: Total knee arthroplasty (TKA) is associated with moderate-to-severe postoperative pain despite multimodal opioid-sparing analgesia. Pain catastrophising or preoperative opioid therapy is associated with increased postoperative pain. Preoperative glucocorticoid improves pain after TKA, but dose-finding studies and benefit in high pain responders are lacking. Methods: A randomised double-blind controlled trial with preoperative high-dose intravenous dexamethasone 1 mg kg−1 or intermediate-dose dexamethasone 0.3 mg kg−1 in 88 patients undergoing TKA with preoperative pain catastrophising score >20 or regular opioid use was designed. The primary outcome was the proportion of patients experiencing moderate-to-severe pain (VAS >30) during a 5 m walk 24 h postoperatively. Secondary outcomes included pain at rest during nights and at passive leg raise, C-reactive protein, opioid use, quality of sleep, Quality of Recovery-15 and Opioid-Related Symptom Distress Scale, readmission, and complications. Results: Moderate-to-severe pain when walking 24 h postoperatively was reduced (high dose vs intermediate dose, 49% vs 79%; P<0.01), along with pain at leg raise at 24 and 48 h (14% vs 29%, P=0.02 and 12% vs 31%, P=0.03, respectively). C-reactive protein was reduced in the high-dose group at both 24 and 48 h (both P<0.01). Quality of Recovery-15 was also improved (P<0.01). Conclusions: When compared with preoperative dexamethasone 0.3 mg kg−1 i.v., dexamethasone 1 mg kg−1 reduced moderate-to-severe pain 24 h after TKA and improved recovery in high pain responders without apparent side-effects. Clinical trial registration: NCT03763734.

Background: Peripheral nerve blocks (PNBs) are increasingly popular in acute ankle fracture surgery but rebound pain may outweigh the benefits. The AnAnkle Trial was designed to assess the postoperative pain profile of PNB anaesthesia compared with spinal anaesthesia (SA). Methods: The AnAnkle Trial was a randomised, two-centre, blinded outcome analysis trial. Eligible adults booked for primary ankle fracture surgery were randomised to PNB or SA. The PNBs were ultrasound-guided popliteal sciatic and saphenous blocks with ropivacaine and SAs were with hyperbaric bupivacaine. Postoperatively, all subjects received paracetamol, ibuprofen, and patient-controlled i.v. morphine for pain. The primary endpoint was 27 h Pain Intensity and Opioid Consumption (PIOC) score. Secondary endpoints included longitudinal pain scores and morphine consumption separately, and questionnaires on quality of recovery. Results: This study enrolled 150 subjects, and the PNB success rate was >94%. PIOC was lower with PNB anaesthesia (median, –26.5% vs +54.3%; P<0.001) and the probability of a better PIOC score with PNB than with SA was 74.8% (95% confidence interval, 67.0–82.6). Pain scores and morphine consumption analysed separately also yielded a clear benefit with PNB, despite substantial rebound pain when PNBs subsided. Quality of recovery scores were similar between groups, but 99% having PNB vs 90% having SA would choose the same anaesthesia form again (P=0.03). Conclusions: PNB anaesthesia was efficient and provided a superior postoperative pain profile compared with SA for acute ankle fracture surgery, despite potentially intense rebound pain after PNB. Clinical trial registration: Clinicaltrialsregister.eu, EudraCT number: 2015-001108-76.

Background: The main disease etiologies requiring emergency high-risk abdominal surgery are intestinal obstruction and perforated viscus and the differences in immune response to these pathologies are largely unexplored. In search of improvement of patient assessment in the perioperative phase, we examined the inflammatory response in this setting, focusing on potential difference in pathophysiology. Methods: The electronic medical records of 487 patients who underwent emergency abdominal surgery from year 2013-2015 for intestinal obstruction and perforated viscus were reviewed. We evaluated the relationship between pre- and postoperative C-reactive protein (CRP) trajectory, fluid balance, and perioperative morbidity and mortality according to type of surgery, intervention, and surgical pathology. Results: A total of 418 patients were included. Pre- and postoperative absolute CRP values were significantly higher in patients with perforated viscus (n = 203) than in intestinal obstruction (n = 215) (P <.0001). Relative changes at hour 6 and POD 1 were non-significant (P =.716 and P =.816 respectively). There was significant association between both pre- (quartile 1 vs 4, OR 5.11; P <.01) and postoperative (quartile 1 vs 4, OR 4.10; P <.001) CRP and adverse outcome, along with fluid balance and adverse outcome in patients with obstruction but not in those with perforation. Fluid balance and CRP had statistically significant positive correlation in patients with obstruction. Conclusions: In this explorative study, a high pre- and postoperative CRP and a high positive fluid balance were associated with worse outcome in patients with intestinal obstruction, but not in patients with perforated viscus. Future studies should address the different inflammatory and fluid trajectories in these specific pathologies.

Background: Severe immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood. Objective: Our aim was to phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome (ARDS). Methods: We consecutively included patients less than 72 hours after intubation following informed consent from their next of kin. Bronchoalveolar lavage fluid was evaluated by microscopy; bronchoalveolar lavage fluid and blood were assessed by 10-color flow cytometry and a multiplex cytokine panel. Results: Four mechanically ventilated patients (aged 40-75 years) with moderate-to-severe COVID-19 ARDS were included. Immature neutrophils dominated in both blood and lungs, whereas CD4 and CD8 T-cell lymphopenia was observed in the 2 compartments. However, regulatory T cells and TH17 cells were found in higher fractions in the lung. Lung CD4 and CD8 T cells and macrophages expressed an even higher upregulation of activation markers than in blood. A wide range of cytokines were expressed at high levels both in the blood and in the lungs, most notably, IL-1RA, IL-6, IL-8, IP-10, and monocyte chemoattactant protein-1, consistent with hyperinflammation. Conclusion: COVID-19 ARDS exhibits a distinct immunologic profile in the lungs, with a depleted and exhausted CD4 and CD8 T-cell population that resides within a heavily hyperinflammatory milieu.

Background: Patients undergoing total knee arthroplasty (TKA)/ total hip arthroplasty (THA) still experience moderate-severe postoperative pain despite optimized pain management regimes. The patients already on opioid treatment and pain catastrophizers (PCs) have a higher risk of postoperative pain. The use of preoperative intravenous high-dose glucocorticoids decreases postoperative pain after TKA and THA, but optimal dose is yet to be found, and the effect on subpopulations at high pain risk is unknown. Aim: To investigate the effect of a higher than previously used dose of glucocorticoids (dexamethasone (DXM)), administered intravenously before surgery, as part of standardized fast-track regimen, on postoperative pain in TKA/THA subgroups. Method: Three separate randomized, double-blinded, controlled trials were planned to compare a new higher dose DXM (1 mg/kg) to the earlier used high-dose DXM (0.3 mg/kg). Study 1: predicted Low Pain TKA; study 2: predicted High Pain Responder (HPR) TKA; study 3: predicted HPR THA. Predicted HPR groups consist of either PCs with PCS-score of ≥ 21 and/or history of ongoing opioid-treatment of 30 mg/day of morphine or equivalents > 30 days. In total, 408 patients were planned for inclusion (160 Low Pain TKA, 88 HPR TKA, 160 HPR THA). Primary outcome : Pain upon ambulation in a 5-meter walk test 24 hours after surgery. Secondary outcomes include use of analgesics, rescue-opioids, antiemetics, cumulated pain, CRP, OR-SDS, QoR-15, quality of sleep, length of stay (LOS), reasons for hospitalization, readmission, morbidity, and mortality. Patients completed follow-up on day 90. Recruiting commenced February 2019 and is expected to finish in September 2020.

Purpose: The patient’s ability to complete their planned physiotherapy session after hip fracture surgery has been proposed as an independent predictor for achieving basic mobility independency upon hospital discharge. However, knowledge of factors limiting mobility is sparse. We therefore examined patient reported factors limiting ability to complete planned physiotherapy sessions as well as limitations for not achieving independency in basic mobility early after hip fracture surgery. Methods: A total of 204 consecutive patients with a hip fracture (mean (SD) age of 80 (9.9) years, 47 patients were admitted from a nursing home) were treated in accordance with a multimodal program. The Cumulated Ambulation Score was used to evaluate the patient’s independency in three basic mobility activities: getting in and out of bed, sit-to-stand-to-sit from a chair and indoor walking. Pre-defined limitations; pain, motor blockade, dizziness, fatigue, nausea, acute cognitive dysfunction and “other limitations”, for not achieving a full Cumulated Ambulation Score or inability to complete planned physiotherapy sessions were noted by the physiotherapist on each of the three first postoperative days. This period was chosen, because of its importance on how well the patients had regained their pre-fracture functional level. Results: Fatigue and hip fracture-related pain were the most frequent reasons for patients not achieving an independent basic mobility level (> 85%) or not fully completing their planned physiotherapy (> 42%) on all three days. At hospital discharge (median day 10), only 54% of the patients had regained their pre-fracture basic mobility level. Conclusion: Based on the patient’s perception, fatigue and pain are the most frequent limitations in not achieving independent basic mobility and not completing physiotherapy after hip fracture surgery. This raises questions whether multimodal peri-operative programs can be further optimized to enhance the early rec