Additive or synergistic analgesic effect of metamizole on standard pain treatment at home after arthroscopic shoulder surgery: A randomised controlled superiority trial.

BACKGROUND: There is growing evidence that the analgesic effect of metamizole is mediated at least partly by central mechanisms, including the endocannabinoid/endovanilloid system. Consequently, metamizole may have additive or even synergistic analgesic effects with paracetamol and nonsteroidal anti-inflammatory drugs (NSAID). OBJECTIVE: This study aimed to assess if triple therapy with metamizole, ibuprofen and paracetamol (MIP) is superior to double therapy with ibuprofen and paracetamol (i.p.) in treating pain at home after ambulatory arthroscopic shoulder surgery. DESIGN/SETTING/PATIENTS/INTERVENTION: In this double-blind, controlled, high-volume single centre, superiority trial, 110 patients undergoing elective ambulatory arthroscopic shoulder surgery were randomised to receive either MIP ( n  = 55) or i.p. ( n  = 55) orally for 4 days between December 2019 and November 2021. Pain intensity at movement and rest, using a numeric rating scale (NRS), perceived pain relief, use of rescue medication and adverse effects of study medication were recorded at the post-anaesthesia care unit (PACU) and on postoperative day (POD) 1 to 4 and 7. Quality of Recovery (QoR) and satisfaction with study medication were measured at POD 7 with telephone follow-up. MAIN OUTCOME MEASURE: The primary outcome measure was postoperative pain intensity on movement measured by an 11-point NRS (where 0 = no pain and 10 = worst pain imaginable) on POD 1. RESULTS: For the primary outcome, superiority of MIP in reducing postoperative pain at movement on POD 1 was not confirmed: mean difference NRS [95% confidence interval (CI), -0.08 (-1.00 to 0.84)]. For pain on movement and at rest, no significant differences were found between groups in the PACU nor on POD 1 to 4 or day 7. Nausea was reported significantly more frequently in the metamizole group (22.6 vs. 58.5; P  < 0.001). Other adverse effects of study medication, rescue opioid consumption, perceived pain relief, QoR at POD 7, and overall patient satisfaction were similar in both groups. CONCLUSION: Clinically, triple oral treatment with metamizole, paracetamol and ibuprofen is not superior to oral paracetamol and ibuprofen in multimodal pain treatment at home after ambulatory arthroscopic shoulder surgery. TRIAL REGISTRATION: European Union Clinical Trials Register 2019-002801-23 and Clinicaltrials.gov NCT04082728.

The analgesic efficacy of forearm versus upper arm intravenous regional anesthesia (Bier's block): A randomized controlled non-inferiority trial.

STUDY OBJECTIVE: This study aimed to assess if a forearm (FA) intravenous regional anesthesia (IVRA) with a lower, less toxic, local anesthetic dosage is non-inferior to an upper arm (UA) IVRA in providing a surgical block in patients undergoing hand and wrist surgery. DESIGN: Observer-blinded, randomized non-inferiority study. SETTING: Operating room. PATIENTS: 280 patients undergoing hand surgery were randomly assigned to UA IVRA (n = 140) or FA IVRA (n = 140). INTERVENTIONS: Forearm IVRA or upper arm IVRA in patients undergoing hand and wrist surgery. MEASUREMENTS: The primary outcome was block success rate of both techniques. Block success was defined as no need of additional analgesics. A second, alternative non-inferiority outcome was defined as no need of conversion to general anesthesia. A difference in success rate of <5% was considered non-inferior. Secondary endpoints were tourniquet pain measured with a Numerical Rating Scale (0-10), satisfaction of patients and surgeons, onset time, surgical time and total OR time. MAIN RESULTS: Non-inferiority of block success rate, defined as no need of additional analgesics or conversion to general anesthesia was inconclusive (5.24%, 95% CI:-4.34%,+14.82%). Non-inferiority of no need of conversion to general anesthesia was confirmed (+0.73%, 95% CI:-0.69%,+2.15%). No differences were observed in onset time (FA: 5 (5, 8) vs UA: 6 (5, 7) min, p = 0.74), surgical time (FA: 8 (5, 12) vs UA: 7 (5, 11) min, p = 0.71), nor total OR stay time (FA: 34 (27, 41) vs UA: 35 (32, 39) min, p = 0.09). Tourniquet pain after 10 min was significantly lower after FA IVRA compared to UA IVRA (FA: 2.00 (0.00, 4.00) vs UA: 3.00 (1.00,5.00) min, p = 0.003). CONCLUSION: We failed to demonstrate non-inferiority of forearm IVRA with a lower dosage of LA in providing a surgical block without rescue opioids and LA. Non-inferiority of no need of conversion to general anesthesia was confirmed.

Evaluation of a comprehensive pre-procedural screening protocol for COVID-19 in times of a high SARS CoV-2 prevalence: a prospective cross-sectional study.

BACKGROUND: To minimise the risk of COVID-19 transmission, an ambulant screening protocol for COVID-19 in patients before admission to the hospital was implemented, combining the SARS CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) on a nasopharyngeal swab, a chest computed tomography (CT) and assessment of clinical symptoms. The aim of this study was to evaluatethe diagnostic yield and the proportionality of this pre-procedural screeningprotocol. METHODS: In this mono-centre, prospective, cross-sectional study, all patients admitted to the hospital between 22nd April 2020 until 14th May 2020 for semi-urgent surgery, haematological or oncological treatment, or electrophysiological investigationunderwent a COVID-19 screening 2 days before their procedure. At a 2-week follow-up, the presence of clinical symptoms was evaluated by telephone as a post-hoc evaluation of the screening approach.Combined positive RT-PCR assay and/or positive chest CT was used as gold standard. Post-procedural outcomes of all patients diagnosed positive for COVID-19 were assessed. RESULTS: In total,528 patients were included of which 20 (3.8%) were diagnosed as COVID-19 positive and 508 (96.2%) as COVID-19 negative. 11 (55.0%) of COVID-19 positive patients had only a positive RT-PCR assay, 3 (15.0%) had only a positive chest CT and 6 (30%) had both a positive RT-PCR assay and chest CT. 10 out of 20 (50.0%) COVID-19 positive patients reported no single clinical symptom at the screening. At 2 week follow-up, 50% of these patients were still asymptomatic. 37.5% of all COVID-19 negative patients were symptomatic at screening. In the COVID-19 negative group without symptoms at screening, 78 (29.3%) patients developed clinical symptoms at a 2-week follow-up. CONCLUSION: This study suggests that routine chest CT and assessment of self-reported symptoms have limited value in the preprocedural COVID-19 screening due to low sensitivity and/or specificity.

Neurological outcome after minimally invasive coronary artery bypass surgery (NOMICS): An observational prospective cohort study.

BACKGROUND/OBJECTIVES: Endoscopic coronary artery bypass grafting (Endo-CABG) is a minimally invasive CABG procedure with retrograde arterial perfusion. The main objective of this study is to assess neurocognitive outcome after Endo-CABG. METHODS/DESIGN: In this prospective observational cohort study, patients were categorised into: Endo-CABG (n = 60), a comparative Percutaneous Coronary Intervention (PCI) group (n = 60) and a healthy volunteer group (n = 60). A clinical neurological examination was performed both pre- and postoperatively, delirium was assessed postoperatively. A battery of 6 neurocognitive tests, Quality of life (QoL) and the level of depressive feelings were measured at baseline and after 3 months. Patient Satisfaction after Endo-CABG was assessed at 3-month follow-up. Primary endpoints were incidence of postoperative cognitive dysfunction (POCD), stroke and delirium after Endo-CABG. Secondary endpoints were QOL, patient satisfaction and the incidence of depressive feelings after Endo-CABG. RESULTS: In total, 1 patient after Endo-CABG (1.72%) and 1 patient after PCI (1.67%) suffered from stroke during the 3-month follow-up. POCD in a patient is defined as a Reliable Change Index ≤-1.645 or Z-score ≤-1.645 in at least two tests, and was found in respectively 5 and 6 patients 3 months after Endo-CABG and PCI. Total incidence of POCD/stroke was not different (PCI: n= 7 [15.9%]; Endo-CABG: n= 6 [13.0%], p = 0.732). ICU delirium after Endo-CABG was found in 5 (8.6%) patients. QoL increased significantly three months after Endo-CABG and was comparable with QoL level after PCI and in the control group. Patient satisfaction after Endo-CABG and PCI was comparable. At follow-up, the level of depressive feelings was decreased in all groups. CONCLUSIONS: The incidence of poor neurocognitive outcome, including stroke, POCD and postoperative ICU delirium until three months after Endo-CABG is low and comparable with PCI. TRIAL REGISTRATION: Registered on ClinicalTrials.gov (NCT02979782).

Impact of implementation of an individualised thromboprophylaxis protocol in critically ill ICU patients with COVID-19: A longitudinal controlled before-after study.

INTRODUCTION: An individualised thromboprophylaxis was implemented in critically ill patients suffering from coronavirus disease 2019 (COVID-19) pneumonia to reduce mortality and improve clinical outcome. The aim of this study was to evaluate the effect of this intervention on clinical outcome. METHODS: In this mono-centric, controlled, before-after study, all consecutive adult patients with confirmed COVID-19 pneumonia admitted to ICU from March 13th to April 20th 2020 were included. A thromboprophylaxis protocol, including augmented LMWH dosing, individually tailored with anti-Xa measurements and twice-weekly ultrasonography screening for DVT, was implemented on March 31th 2020. Primary endpoint is one-month mortality. Secondary outcomes include two-week and three-week mortality, the incidence of VTE, acute kidney injury and continuous renal replacement therapy (CRRT). Multiple regression modelling was used to correct for differences between the two groups. RESULTS: 46 patients were included in the before group, 26 patients in the after group. One month mortality decreased from 39.13% to 3.85% (p < 0.001). After correction for confounding variables, one-month mortality was significantly higher in the before group (p = 0.02, OR 8.86 (1.46, 53.75)). The cumulative incidence of VTE and CRRT was respectively 41% and 30.4% in the before group and dropped to 15% (p = 0.03) and 3.8% (p = 0.01), respectively. After correction for confounding variables, risk of VTE (p = 0.03, 6.01 (1.13, 32.12)) and CRRT (p = 0.02, OR 19.21 (1.44, 255.86)) remained significantly higher in the before group. CONCLUSION: Mortality, cumulative risk of VTE and need for CRRT may be significantly reduced in COVID-19 patients by implementation of a more aggressive thromboprophylaxis protocol. Future research should focus on confirmation of these results in a randomized design and on uncovering the mechanisms underlying these observations. REGISTRATION NUMBER: NCT04394000.

Metamizole vs. ibuprofen at home after day case surgery: A double-blind randomised controlled noninferiority trial.

BACKGROUND: NSAIDs and paracetamol are the cornerstones of pain treatment after day case surgery. However, NSAIDs have numerous contraindications and consequently are not suitable in up to 25% of patients. Metamizole is a non-opioid compound with a favourable gastro-intestinal and cardiovascular profile compared with NSAIDs. OBJECTIVES: The study aimed to assess if a combination of metamizole and paracetamol is noninferior to a combination of ibuprofen and paracetamol in treating pain at home after painful day case surgery. DESIGN: A double-blind randomised controlled trial. SETTING: Single centre. PATIENTS: Two hundred patients undergoing elective ambulatory haemorrhoid surgery, arthroscopic shoulder or knee surgery, or inguinal hernia repair. INTERVENTION: Patients were randomly allocated to receive either metamizole and paracetamol (n = 100) or ibuprofen and paracetamol (n = 100) orally for four days. MAIN OUTCOME MEASURES: Average postoperative pain intensity using a numerical rating scale and use of rescue medication were measured in the postanaesthesia care unit (PACU) and on postoperative days (POD) 1 to 3. A difference in mean numerical rating scale score of 1 point or less was considered noninferior. Adverse effects of study medication and satisfaction with study medication were measured on PODs 1 to 3 by telephone follow-up. RESULTS: In the PACU, the difference in mean ±â€ŠSD pain score between metamizole and paracetamol and ibuprofen and paracetamol was 0.85 ±â€Š0.78. From POD 1 to 3, this difference was lower than 1, resulting in noninferiority. Rescue opioid consumption in the PACU and on PODs 1 and 3 was not significantly different between treatment groups. Rescue opioid consumption on POD2 was significantly higher in the ibuprofen and paracetamol group (P = 0.042). Adverse effects of study medication and overall patient satisfaction were similar in both groups. CONCLUSION: Paracetamol/metamizole and paracetamol/ibuprofen are equally effective in treatment of acute postoperative pain at home after ambulatory surgery with comparable patient satisfaction levels. TRIAL REGISTRATION: European Union Clinical Trials Register 2015-003987-35.

The analgesic efficacy of intravenous regional anesthesia with a forearm versus conventional upper arm tourniquet: a systematic review.

BACKGROUND: The main objective of this review is to perform a systematic review and meta-analysis of the existing evidence related to the analgesic efficacy with the use of conventional, upper arm intravenous regional anesthesia (IVRA) as compared to a modified, forearm IVRA in adult patients undergoing procedures on the distal upper extremity. METHODS: MEDLINE, EMBASE and CENTRAL (Cochrane) databases were searched for randomized controlled trials published in English, French, Dutch, German or Spanish language. Primary outcomes of interest including description of quality level of anesthesia and onset of sensory block were assessed for this review. Dosage of the local anesthetic, local anesthetic toxicity and need for sedation due to tourniquet pain were considered as secondary outcomes. RESULTS: Our literature search yielded 3 papers for qualitative synthesis. Four other articles were added into a parallel analysis of 7 reports that provided data on the incidence of complications and success rate after forearm IVRA. Forearm IVRA was found to be as efficient as upper arm IVRA (RR = 0.98 [0.93, 1.05], P = 0.78), but comes with the advantage of a lower need for sedation due to less tourniquet pain. CONCLUSION: Our results demonstrate that forearm IVRA is as effective in providing a surgical block as compared to a conventional upper arm IVRA, even with a reduced, non-toxic dosage of local anesthetic. No severe complications were associated with the use of a forearm IVRA. Other benefits of the modified technique include a faster onset of sensory block, better tourniquet tolerance and a dryer surgical field. REGISTRATION OF THE SYSTEMATIC REVIEW: A review protocol was published in the PROSPERO register in November 2015 with registration number CRD42015029536 .

Selective Suprascapular and Axillary Nerve Block Versus Interscalene Plexus Block for Pain Control After Arthroscopic Shoulder Surgery: A Noninferiority Randomized Parallel-Controlled Clinical Trial.

BACKGROUND AND OBJECTIVES: This randomized trial aimed to assess if a combined suprascapular-axillary nerve block (SSB) is noninferior (margin = 1.3 on a 0- to 10-point scale) to interscalene block (ISB) in treating pain after arthroscopic shoulder surgery. Secondary end points included opioid consumption, dyspnea, discomfort associated with muscle weakness, and patient satisfaction. METHODS: One hundred patients undergoing arthroscopic shoulder surgery were randomized to receive ultrasound-guided ISB (n = 50) or SSB (n = 50). Pain intensity at rest, dyspnea, and discomfort were recorded upon arrival in the recovery room, discharge to the ward, and at 4, 8, and 24 hours after surgery. Piritramide consumption was recorded for the first 24 hours. Patient satisfaction was assessed on the second postoperative day. RESULTS: During the first 4 hours after surgery, the difference in mean pain score between SSB and ISB was higher than 2.5 (±0.8). The difference gradually decreased to 1.1 (±1.0) at 8 hours before resulting in noninferiority during the night and at 24 hours. Piritramide consumption was significantly higher in the SSB group in the first 8 hours. The incidence of dyspnea and discomfort was higher after ISB. Treatment satisfaction was similar in both groups. CONCLUSIONS: Suprascapular-axillary nerve block is inferior to ISB in terms of analgesia and opioid requirement in the immediate period after arthroscopic shoulder surgery but is associated with a lower incidence of dyspnea and discomfort. The difference in pain and opioid consumption gradually decreases as the blocks wear off in order to reach similar pain scores during the first postoperative night and at 24 hours. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, identifier NCT02415088.

Neurological outcome after minimal invasive coronary artery surgery (NOMICS): protocol for an observational prospective cohort study.

INTRODUCTION: Adverse neurocognitive outcomes are still an important cause of morbidity and mortality after cardiac surgery. The most common neurocognitive disorders after conventional cardiac surgery are postoperative cognitive dysfunction (POCD), stroke and delirium. Minimal invasive cardiac procedures have recently been introduced into practice. Endoscopic coronary artery bypass grafting (Endo-CABG) is a minimal invasive cardiac procedure based on the conventional CABG procedure. Neurocognitive outcome after minimal invasive cardiac surgery, including Endo-CABG, has never been studied. Therefore, the main objective of this study is to examine neurocognitive outcome after Endo-CABG. METHODS AND ANALYSIS: We will perform a prospective observational cohort study including 150 patients. Patients are categorised into three groups: (1) patients undergoing Endo-CABG, (2) patients undergoing a percutaneous coronary intervention and (3) a healthy volunteer group. All patients in the Endo-CABG group will be treated following a uniform, standardised protocol. To assess neurocognitive outcome after surgery, a battery of six neurocognitive tests will be administered at baseline and at 3-month follow-up. In the Endo-CABG group, a neurological examination will be performed at baseline and postoperatively and delirium will be scored at the intensive care unit. Quality of life (QOL), anxiety and depression will be assessed at baseline and at 3-month follow-up. Satisfaction with Endo-CABG will be assessed at 3-month follow-up. Primary endpoints are the incidence of POCD, stroke and delirium after Endo-CABG. Secondary endpoints are QOL after Endo-CABG, patient satisfaction with Endo-CABG and the incidence of anxiety and depression after Endo-CABG. ETHICS AND DISSEMINATION: The neurological outcome after minimal invasive coronary artery surgery study has received approval of the Jessa Hospital ethics board. It is estimated that the trial will be executed from December 2016 to January 2018, including enrolment and follow-up. Analysis of data, followed by publication of the results, is expected in 2018. TRIAL REGISTRATION NUMBER: NCT02979782.

Metamizole versus ibuprofen at home after day surgery: study protocol for a randomised controlled trial.

BACKGROUND: Postoperative pain and, in a more extended perspective, quality of recovery (QOR) should be considered the principal endpoints after day surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are a cornerstone of pain treatment after painful day surgery. Nevertheless, NSAIDs are not always sufficiently effective, have numerous contraindications, and consequently are not suitable in up to 25 % of all patients. Metamizole is a non-opioid compound with a favourable gastrointestinal, cardiovascular and cerebrovascular profile compared to NSAIDs. The aim of this study is to assess if a combination of metamizole and paracetamol is non-inferior to a combination of ibuprofen and paracetamol in the treatment of acute postoperative pain at home after painful day case surgery. In addition, we aim to assess and compare quality of recovery (QOR) profiles of both groups. METHODS/DESIGN: This is an investigator-initiated, double-blind, randomised controlled, non-inferiority trial. A total of 200 patients undergoing elective haemorrhoid surgery, arthroscopic shoulder or knee surgery, or inguinal hernia repair in a day care setting will be randomised to receive either a combination of metamizole and paracetamol (MP) or a combination of ibuprofen and paracetamol (IP). Participants will take study medication orally for 4 days. Primary endpoints are average postoperative pain intensity measured by an 11-point Numeric Rating Scale at postoperative day 1 and QOR profile measured by the Functional Recovery Index (FRI), the 1-item Global Surgical Recovery (GSR) index and the EuroQol (EQ-5D) questionnaire at days 1, 2, 3, 4, 7, 14 and 28 postoperatively. Secondary outcomes include compliance with study medication, adverse effects of study medication, use of rescue medication and satisfaction with study medication, surgery and hospital care and telephone follow-up. DISCUSSION: This study will provide clinical evidence on the analgesic efficacy and safety of a combination of metamizole and paracetamol in treating postoperative pain at home after painful day surgery. This study may also provide an insight into QOR profile after four different types of surgery and into the interrelationship between three different instruments used to assess QOR. TRIAL STATUS: Recruitment is currently ongoing. TRIAL REGISTRATION: European Union Clinical Trials Register 2015-003987-35 . Registered 10 November 2015.

Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease.

PURPOSE: Histiocytoses are rare disorders with heterogeneous prognosis. BRAF(V600E) mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD. PATIENTS AND METHODS: Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAF(V600E) mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]). RESULTS: All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe. CONCLUSION: Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.