Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

Genome-wide association study suggests a critical contribution of the adaptive immune system to chronic post-surgical pain.

Chronic post-surgical pain affects a large proportion of people undergoing surgery, delaying recovery time and worsening quality of life. Although many environmental variables have been established as risk factors, less is known about genetic risk. To uncover genetic risk factors we performed genome-wide association studies in post-surgical cohorts of five surgery types- hysterectomy, mastectomy, abdominal, hernia, and knee- totaling 1350 individuals. Genetic associations between post-surgical chronic pain levels on a numeric rating scale (NRS) and additive genetic effects at common SNPs were evaluated. We observed genome-wide significant hits in almost all cohorts that displayed significance at the SNP, gene, and pathway levels. The cohorts were then combined via a GWAS meta-analysis framework for further analyses. Using partitioned heritability, we found that loci at genes specifically expressed in the immune system carried enriched heritability, especially genes related to B and T cells. The relevance of B cells in particular was then demonstrated in mouse postoperative pain assays. Taken altogether, our results suggest a role for the adaptive immune system in chronic post-surgical pain.

Rationale and Design of the ISOLATION Study: A Multicenter Prospective Cohort Study Identifying Predictors for Successful Atrial Fibrillation Ablation in an Integrated Clinical Care and Research Pathway.

Introduction: Continuous progress in atrial fibrillation (AF) ablation techniques has led to an increasing number of procedures with improved outcome. However, about 30-50% of patients still experience recurrences within 1 year after their ablation. Comprehensive translational research approaches integrated in clinical care pathways may improve our understanding of the complex pathophysiology of AF and improve patient selection for AF ablation. Objectives: Within the "IntenSive mOlecular and eLectropathological chAracterization of patienTs undergoIng atrial fibrillatiOn ablatioN" (ISOLATION) study, we aim to identify predictors of successful AF ablation in the following domains: (1) clinical factors, (2) AF patterns, (3) anatomical characteristics, (4) electrophysiological characteristics, (5) circulating biomarkers, and (6) genetic background. Herein, the design of the ISOLATION study and the integration of all study procedures into a standardized pathway for patients undergoing AF ablation are described. Methods: ISOLATION (NCT04342312) is a two-center prospective cohort study including 650 patients undergoing AF ablation. Clinical characteristics and routine clinical test results will be collected, as well as results from the following additional diagnostics: determination of body composition, pre-procedural rhythm monitoring, extended surface electrocardiogram, biomarker testing, genetic analysis, and questionnaires. A multimodality model including a combination of established predictors and novel techniques will be developed to predict ablation success. Discussion: In this study, several domains will be examined to identify predictors of successful AF ablation. The results may be used to improve patient selection for invasive AF management and to tailor treatment decisions to individual patients.

High-flow nasal cannula versus standard low-flow nasal cannula during deep sedation in patients undergoing radiofrequency atrial fibrillation catheter ablation: a single-centre randomised controlled trial.

BACKGROUND: To our knowledge, there are few trials studying the effect of high-flow nasal cannula (HFNC) during deep sedation. Our hypothesis is that high-flow nasal cannula (HFNC) will prevent hypoxemia and desaturation as compared to low-flow nasal cannula (LFNC) during prolonged deep sedation in patients with atrial fibrillation undergoing radiofrequency catheter ablation (RFCA). METHODS: A single-centre, randomised controlled trial with HFNC as the intervention and LFNC as the control group. A total of 94 adult patients per group undergoing elective radiofrequency atrial fibrillation catheter ablation under deep sedation. will be included. The primary outcome is the lowest oxygen saturation (SpO2). Secondary outcomes are as follows: the duration of lowest SpO2, cross over from oxygen therapy in both directions, incidence of SpO2 below 90% > 60 seconds, adverse sedation events, adverse effects of HFNC, mean CO2, peak CO2 and patients experience with oxygen therapy. The study will take place during the 2-day admission period for RFCA. Patients can fill out their questionnaires in the first week after treatment. DISCUSSION: HFNC is increasingly used as a technique for oxygen delivery in procedural sedation and analgesia. We hypothesise that HFNC is superior to the standard treatment LFNC in patients under deep sedation with respect to the incidence of desaturation. To our knowledge, there are no adequately powered clinical trial studies on the effects of HFNC in prolonged deep sedation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04842253. Registered on 04 April 2021.

Validation of the PreOperative Score to predict Post-Operative Mortality (POSPOM) in Dutch non-cardiac surgery patients.

BACKGROUND: Standardized risk assessment tools can be used to identify patients at higher risk for postoperative complications and death. In this study, we validate the PreOperative Score to predict Post-Operative Mortality (POSPOM) for in-hospital mortality in a large cohort of non-cardiac surgery patients. In addition, the performance of POSPOM to predict postoperative complications was studied. METHODS: Data from the control cohort of the TRACE (routine posTsuRgical Anesthesia visit to improve patient outComE) study was analysed. POSPOM scores for each patient were calculated post-hoc. Observed in-hospital mortality was compared with predicted mortality according to POSPOM. Discrimination was assessed by receiver operating characteristic curves with C-statistics for in-hospital mortality and postoperative complications. To describe the performance of POSPOM sensitivity, specificity, negative predictive values, and positive predictive values were calculated. For in-hospital mortality, calibration was assessed by a calibration plot. RESULTS: In 2490 patients, the observed in-hospital mortality was 0.5%, compared to 1.3% as predicted by POSPOM. 27.1% of patients had at least one postoperative complication of which 22.4% had a major complication. For in-hospital mortality, POSPOM showed strong discrimination with a C-statistic of 0.86 (95% CI, 0.78-0.93). For the prediction of complications, the discrimination was poor to fair depending on the severity of the complication. The calibration plot showed poor calibration of POSPOM with an overestimation of in-hospital mortality. CONCLUSION: Despite the strong discriminatory performance, POSPOM showed poor calibration with an overestimation of in-hospital mortality. Performance of POSPOM for the prediction of any postoperative complication was poor but improved according to severity.

Differences and Similarities Among COVID-19 Patients Treated in Seven ICUs in Three Countries Within One Region: An Observational Cohort Study.

OBJECTIVES: To investigate healthcare system-driven variation in general characteristics, interventions, and outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU within one Western European region across three countries. DESIGN: Multicenter observational cohort study. SETTING: Seven ICUs in the Euregio Meuse-Rhine, one region across Belgium, The Netherlands, and Germany. PATIENTS: Consecutive COVID-19 patients supported in the ICU during the first pandemic wave. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographic and clinical characteristics, laboratory values, and outcome data were retrieved after ethical approval and data-sharing agreements. Descriptive statistics were performed to investigate country-related practice variation. From March 2, 2020, to August 12, 2020, 551 patients were admitted. Mean age was 65.4 ± 11.2 years, and 29% were female. At admission, Acute Physiology and Chronic Health Evaluation II scores were 15.0 ± 5.5, 16.8 ± 5.5, and 15.8 ± 5.3 (p = 0.002), and Sequential Organ Failure Assessment scores were 4.4 ± 2.7, 7.4 ± 2.2, and 7.7 ± 3.2 (p < 0.001) in the Belgian, Dutch, and German parts of Euregio, respectively. The ICU mortality rate was 22%, 42%, and 44%, respectively (p < 0.001). Large differences were observed in the frequency of organ support, antimicrobial/inflammatory therapy application, and ICU capacity. Mixed-multivariable logistic regression analyses showed that differences in ICU mortality were independent of age, sex, disease severity, comorbidities, support strategies, therapies, and complications. CONCLUSIONS: COVID-19 patients admitted to ICUs within one region, the Euregio Meuse-Rhine, differed significantly in general characteristics, applied interventions, and outcomes despite presumed genetic and socioeconomic background, admission diagnosis, access to international literature, and data collection are similar. Variances in healthcare systems' organization, particularly ICU capacity and admission criteria, combined with a rapidly spreading pandemic might be important drivers for the observed differences. Heterogeneity between patient groups but also healthcare systems should be presumed to interfere with outcomes in coronavirus disease 2019.

Impact of Procedural Sedation on the Clinical Outcome of Microelectrode Recording Guided Deep Brain Stimulation in Patients with Parkinson's Disease.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) has become a routine treatment of advanced Parkinson's disease (PD). DBS surgery is commonly performed under local anesthesia (LA) to obtain reliable microelectrode recordings. However, procedural sedation and/or analgesia (PSA) is often desirable to improve patient comfort. The impact of PSA in addition to LA on outcome is largely unknown. Therefore, we performed an observational study to assess the effect of PSA compared to LA alone during STN DBS surgery on outcome in PD patients. METHODS: Seventy PD patients (22 under LA, 48 under LA + PSA) scheduled for STN DBS implantation were included. Dexmedetomidine, clonidine or remifentanil were used for PSA. The primary outcome was the change in Movement Disorders Society Unified Parkinson's Disease Rating Score III (MDS-UPDRS III) and levodopa equivalent daily dosage (LEDD) between baseline, one month before surgery, and twelve months postoperatively. Secondary outcome measures were motor function during activities of daily living (MDS-UPDRS II), cognitive alterations and surgical adverse events. Postoperative assessment was conducted in "on" stimulation and "on" medication conditions. RESULTS: At twelve months follow-up, UPDRS III and UPDRS II scores in "on" medication conditions were similar between the LA and PSA groups. The two groups showed a similar LEDD reduction and an equivalent decline in executive function measured by the Stroop Color-Word Test, Trail Making Test-B, and verbal fluency. The incidence of perioperative and postoperative adverse events was similar between groups. CONCLUSION: This study demonstrates that PSA during STN DBS implantation surgery in PD patients was not associated with differences in motor and non-motor outcome after twelve months compared with LA only.

One-month recovery profile and prevalence and predictors of quality of recovery after painful day case surgery: Secondary analysis of a randomized controlled trial.

BACKGROUND/OBJECTIVES: This study aimed to study one-month recovery profile and to identify predictors of Quality of Recovery (QOR) after painful day surgery and investigate the influence of pain therapy on QOR. METHODS/DESIGN: This is a secondary analysis of a single-centre, randomised controlled trial of 200 patients undergoing ambulatory haemorrhoid surgery, arthroscopic shoulder or knee surgery, or inguinal hernia repair between January 2016 and March 2017. Primary endpoints were one-month recovery profile and prevalence of poor/good QOR measured by the Functional Recovery Index (FRI), the Global Surgical Recovery index and the EuroQol questionnaire at postoperative day (POD) 1 to 4, 7, 14 and 28. Multiple logistic regression analysis was performed to determine predictors of QOR at POD 7, 14, and 28. Differences in QOR between pain treatment groups were analysed using the Mann-Whitney U test. RESULTS: Four weeks after haemorrhoid surgery, inguinal hernia repair, arthroscopic knee and arthroscopic shoulder surgery, good QOR was present in 71%, 76%, 57% and 24% respectively. Poor QOR was present in 5%, 0%, 7% and 29%, respectively. At POD 7 and POD 28, predictors for poor/intermediate QOR were type of surgery and a high postoperative pain level at POD 4. Male gender was another predictor at POD 7. Female gender and having a paid job were also predictors at POD 28. Type of surgery and long term fear of surgery were predictors at POD 14. No significant differences in total FRI scores were found between the two different pain treatment groups. CONCLUSIONS: The present study shows a procedure-specific variation in recovery profile in the 4-week period after painful day surgery. The best predictors for short-term (POD 7) and long-term (POD 28) poor/intermediate QOR were a high postoperative pain level at POD 4 and type of surgery. Different pain treatment regimens did not result in differences in recovery profile. TRIAL REGISTRATION: European Union Clinical Trials Register 2015-003987-35.

Influence of Anesthesia and Clinical Variables on the Firing Rate, Coefficient of Variation and Multi-Unit Activity of the Subthalamic Nucleus in Patients with Parkinson's Disease.

BACKGROUND: Microelectrode recordings (MER) are used to optimize lead placement during subthalamic nucleus deep brain stimulation (STN-DBS). To obtain reliable MER, surgery is usually performed while patients are awake. Procedural sedation and analgesia (PSA) is often desirable to improve patient comfort, anxiolysis and pain relief. The effect of these agents on MER are largely unknown. The objective of this study was to determine the effects of commonly used PSA agents, dexmedetomidine, clonidine and remifentanil and patient characteristics on MER during DBS surgery. METHODS: Data from 78 patients with Parkinson's disease (PD) who underwent STN-DBS surgery were retrospectively reviewed. The procedures were performed under local anesthesia or under PSA with dexmedetomidine, clonidine or remifentanil. In total, 4082 sites with multi-unit activity (MUA) and 588 with single units were acquired. Single unit firing rates and coefficient of variation (CV), and MUA total power were compared between patient groups. RESULTS: We observed a significant reduction in MUA, an increase of the CV and a trend for reduced firing rate by dexmedetomidine. The effect of dexmedetomidine was dose-dependent for all measures. Remifentanil had no effect on the firing rate but was associated with a significant increase in CV and a decrease in MUA. Clonidine showed no significant effect on firing rate, CV or MUA. In addition to anesthetic effects, MUA and CV were also influenced by patient-dependent variables. CONCLUSION: Our results showed that PSA influenced neuronal properties in the STN and the dexmedetomidine (DEX) effect was dose-dependent. In addition, patient-dependent characteristics also influenced MER.

Neurophysiological and paraspinal oximetry monitoring to detect spinal cord ischemia in patients during and after descending aortic repair: An international multicenter explorative study.

BACKGROUND: During descending aortic repair, critically decreased blood flow to the myelum can result in ischemic spinal cord injury and transient or permanent paraplegia. Assessment of motor evoked potentials (MEPs) has been shown to be a valuable tool which allows to detect spinal cord ischemia (SCI) intraoperatively within a therapeutic window suitable to prevent progression to paraparesis or paraplegia. MEP monitoring is not feasible during postoperative care in the awakening patient. Therefore, ancillary techniques to monitor integrity of spinal cord function are needed to detect delayed spinal cord ischemia. OBJECTIVE: The purpose of this study is to evaluate whether assessment of long loop reflexes (LLR; F-waves) and paraspinal muscle oximetry using Near-Infrared Spectroscopy (NIRS) are feasible and valid in detecting delayed SCI. METHODS: We aim to include patients from three tertiary referral centers undergoing aortic repair with MEP monitoring in this study.F-wave measurements and paraspinal NIRS oximetry will be operated intra- and postoperatively. Measurement characteristics and feasibility will be assessed in the first 25 patients. Subsequently, a second cohort of 75 patients will be investigated to determine the sensitivity and specificity of F-waves and NIRS in detecting perioperative SCI. In this context for the MEP group SCI is defined intraoperatively as significant MEP changes and postoperatively as newly developed paraplegia. CONCLUSIONS: A clinical study design and protocol is proposed to assess if F-waves and/or NIRS-based paraspinal oximetry are feasible and valid in detecting and monitoring for occurrences of delayed SCI.

Anesthetic management during endovascular treatment of acute ischemic stroke in the MR CLEAN Registry.

OBJECTIVE: To compare outcomes after endovascular treatment (EVT) for acute ischemic stroke with 3 different types of anesthetic management in clinical practice, as anesthetic management may influence functional outcome. METHODS: Data of patients with an anterior circulation occlusion, included in the Dutch nationwide, prospective Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry between March 2014 and June 2016, were analyzed. Patients were divided into 3 groups defined by anesthetic technique performed during EVT: local anesthesia only (LA), general anesthesia (GA), or conscious sedation (CS). Primary outcome was the modified Rankin Scale score at 90 days. To compare functional outcome between groups, we estimated a common odds ratio (OR) with ordinal logistic regression, adjusted for age, sex, prestroke modified Rankin Scale score, baseline NIH Stroke Scale score, collaterals, and time from onset to arrival at intervention center. RESULTS: A total of 1,376 patients were included. Performed anesthetic technique was LA in 821 (60%), GA in 381 (28%), and CS in 174 (13%) patients. Compared to LA, both GA and CS were associated with worse functional outcome on the modified Rankin Scale score at 90 days (GA cORadj 0.75; 95% confidence interval [CI] 0.58-0.97; CS cORadj 0.45; 95% CI 0.33-0.62). CS was associated with worse functional outcome than GA (cORadj 0.60; 95% CI 0.42-0.87). CONCLUSIONS: LA is associated with better functional outcome than systemic sedation in patients undergoing EVT for acute ischemic stroke. Whereas LA had a clear advantage over CS, this was less prominent compared to GA. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with acute ischemic stroke undergoing EVT, LA improves functional outcome compared to GA or CS.

Effect of Anesthesia on Microelectrode Recordings during Deep Brain Stimulation Surgery in Tourette Syndrome Patients.

BACKGROUND: Deep brain stimulation (DBS) is an accepted treatment for patients with medication-resistant Tourette syndrome (TS). Sedation is commonly required during electrode implantation to attenuate anxiety, pain, and severe tics. Anesthetic agents potentially impair the quality of microelectrode recordings (MER). Little is known about the effect of these anesthetics on MER in patients with TS. We describe our experience with different sedative regimens on MER and tic severity in patients with TS. METHODS: The clinical records of all TS patients who underwent DBS surgery between 2010 and 2018 were reviewed. Demographic data, stimulation targets, anesthetic agents, perioperative complications, and MER from each hemisphere were collected and analyzed. Single-unit activity was identified by filtering spiking activity from broadband MER data and principal component analysis with K-means clustering. Vocal and motor tics which caused artifacts in the MER data were manually selected using visual and auditory inspection. RESULTS: Six patients underwent bilateral DBS electrode implantation. In all patients, the target was the anterior internal globus pallidus. Patient comfort and hemodynamic and respiratory stability were maintained with conscious sedation with one or more of the following anesthetic drugs: propofol, midazolam, remifentanil, clonidine, and dexmedetomidine. Good quality MER and clinical testing were obtained in 9 hemispheres of 6 patients. In 3 patients, MER quality was poor on one side. CONCLUSION: Cautiously applied sedative drugs can provide patient comfort, hemodynamic and respiratory stability, and suppress severe tics, with minimal interference with MER.

Heart Failure in Adult Patients with Congenital Heart Disease.

Adult patients with congenital heart disease are a complex population with a variety of pathophysiologic conditions based on the anatomy and type of surgery or intervention performed, usually during the first years of life. Nowadays, the majority of patients survive childhood and present for a number of noncardiac surgeries or interventions needing appropriate perioperative management. Heart failure is a major contributing factor to perioperative morbidity and mortality. In this review, we present an overview of the most common types of adult patients with congenital heart disease and actual knowledge on therapy and specific risks in this challenging patient population.

Genetic polymorphisms and prediction of chronic post-surgical pain after hysterectomy-a subgroup analysis of a multicenter cohort study.

BACKGROUND: Chronic post-surgical pain (CPSP) is a serious problem. Clinical and psychological variables have not been able to explain all observed variance in prevalence and severity of CPSP. The first objective is to determine the association between genetic polymorphisms and the prevalence of CPSP after hysterectomy. The second objective is to analyze if the implementation of genetic polymorphisms into a previously performed clinical and psychological predictor analysis on the development of CPSP after hysterectomy will improve its discriminatory power. METHODS: A prospective multicenter cohort study was performed in patients undergoing hysterectomy for benign indication. Clinical and psychological variables were collected by questionnaires in the week before surgery, post-operatively up to day 4, 3 and 12 months after hysterectomy. Blood was collected and 16 polymorphisms previously suggested to be correlated to CPSP (COMT, GCH1, KCNS1, CACNG2, and OPRM1) were genotyped. Logistic regression analyses were performed. RESULTS: Three hundred and forty-five patients were available for the genetic analyses. The prevalence of CPSP 3 months post-operatively was 10.5% and after 12 months 7.9%. The polymorphism rs4818 within the COMT gene was associated with the prevalence of CPSP after 3 months. No polymorphisms were associated with CPSP after 12 months. The addition of rs4818 to the prediction model did not change its discriminatory power significantly. CONCLUSION: The rs4818 polymorphism within the COMT gene was associated with the prevalence of CPSP 3 months after hysterectomy, but the implementation of rs4818 into the prediction model did not significantly improve the chance of identifying hysterectomy patients at risk for CPSP.

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.

Shifts of Transfusion Demand in Cardiac Surgery After Implementation of Rotational Thromboelastometry-Guided Transfusion Protocols: Analysis of the HEROES-CS (HEmostasis Registry of patiEntS in Cardiac Surgery) Observational, Prospective Open Cohort Database.

OBJECTIVES: Rotational thromboelastometry (ROTEM)-guided transfusion algorithms in cardiac surgery have been proven to be successful in reducing blood loss in randomized controlled trials. Using an institutional hemostasis registry of patients in cardiac surgery (HEROES-CS), the authors hypothesized that the use of ROTEM-guided transfusion algorithms would save blood products and overall costs in cardiac surgery in every day practice. DESIGN: Observational, prospective open cohort database. SETTING: Single-center academic hospital. PARTICIPANTS: Cardiac surgery patients. INTERVENTIONS: Implementation of ROTEM-guided bleeding management. MEASUREMENTS AND MAIN RESULTS: A classical-guided algorithm and a ROTEM-guided algorithm were used for patient blood management in 2 cohorts. Primary outcome was the use and amount of blood products and hemostatic medication. Secondary outcomes were amount of rethoracotomies, length of stay, and 30-day mortality. Finally, costs and savings were calculated. The classical-guided cohort comprised 204 patients, and ROTEM-guided cohort comprised 151 patients. Baseline characteristics showed excellent similarities after propensity score matching of 202 patients. Blood loss was lower after ROTEM guidance (p < 0.001). Absolute risk reduction was 17% for red blood cells (p = 0.024), 12% for fresh frozen plasma (p = 0.019), and 4% for thrombocyte concentrates (p = 0.582). More tranexamic acid was given, but not more fibrinogen concentrate, while desmopressin was given less often. Hospital length of stay was reduced by an overall median of 2 and a mean of 4 days (p < 0.001). Mortality and rethoracotomy rates were not affected. Potential savings were about €4,800 ($5,630) per patient. CONCLUSIONS: Implementation of a ROTEM-guided transfusion algorithm in cardiac surgery patients reduced the use of blood products and hemostatic medication, hereby saving costs. Reductions in mortality and rethoracotomy rates could not be found.

TRACE (Routine posTsuRgical Anesthesia visit to improve patient outComE): a prospective, multicenter, stepped-wedge, cluster-randomized interventional study.

BACKGROUND: Perioperative complications occur in 30-40% of non-cardiac surgical patients and are the leading cause of early postoperative morbidity and mortality. Regular visits by trained health professionals may decrease the incidence of complications and mortality through earlier detection and adequate treatment of complications. Until now, no studies have been performed on the impact of routine postsurgical anesthesia visits on the incidence of postoperative complications and mortality. METHODS: TRACE is a prospective, multicenter, stepped-wedge cluster randomized interventional study in academic and peripheral hospitals in the Netherlands. All hospitals start simultaneously with a control phase in which standard care is provided. Sequentially, in a randomized order, hospitals cross over to the intervention phase in which patients at risk are routinely followed up by an anesthesia professional at postoperative days 1 and 3, aiming to detect and prevent or treat postoperative complications. We aim to include 5600 adult patients who are at high risk of developing complications. The primary outcome variable is 30-day postoperative mortality. Secondary outcomes include incidence of postoperative complications and postoperative quality of life up to one year following surgery. Statistical analyses will be performed to compare the control and intervention cohorts with multilevel linear and logistic regression models, adjusted for temporal trends and for clusters (hospitals). The time horizon of the economic (cost-effectiveness) evaluation will be 30 days and one year following surgery. DISCUSSION: TRACE is the first to study the effects of a routine postoperative visit by an anesthesia healthcare professional on mortality and cost-effectiveness of surgical patients. If the intervention proves to be beneficial for the patient and cost-effective, the stepped-wedge design ensures direct implementation in the participating hospitals. TRIAL REGISTRATION: Nederlands Trial Register/Netherlands Trial Registration, NTR5506 . Registered on 02 December 2015.