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.

Excessive Oxygen Administration in High-Risk Patients Admitted to Medical and Surgical Wards Monitored by Wireless Pulse Oximeter.

The monitoring of oxygen therapy when patients are admitted to medical and surgical wards could be important because exposure to excessive oxygen administration (EOA) may have fatal consequences. We aimed to investigate the association between EOA, monitored by wireless pulse oximeter, and nonfatal serious adverse events (SAEs) and mortality within 30 days. We included patients in the Capital Region of Copenhagen between 2017 and 2018. Patients were hospitalized due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) or after major elective abdominal cancer surgery, and all were treated with oxygen supply. Patients were divided into groups by their exposure to EOA: no exposure, exposure for 1-59 min or exposure over 60 min. The primary outcome was SAEs or mortality within 30 days. We retrieved data from 567 patients for a total of 43,833 h, of whom, 63% were not exposed to EOA, 26% had EOA for 1-59 min and 11% had EOA for ≥60 min. Nonfatal SAEs or mortality within 30 days developed in 24%, 12% and 22%, respectively, and the adjusted odds ratio for this was 0.98 (95% CI, 0.96-1.01) for every 10 min. increase in EOA, without any subgroup effects. In conclusion, we did not observe higher frequencies of nonfatal SAEs or mortality within 30 days in patients exposed to excessive oxygen administration.

Continuous Glucose Monitoring Reveals Perioperative Hypoglycemia in Most Patients With Diabetes Undergoing Major Surgery: A Prospective Cohort Study.

OBJECTIVE: To investigate the frequency and duration of hypo- and hyperglycemia, assessed by continuous glucose monitoring (CGM) during and after major surgery, in departments with implemented diabetes care protocols. SUMMARY BACKGROUND DATA: Inadequate glycemic control in the perioperative period is associated with serious adverse events, but monitoring currently relies on point blood glucose measurements, which may underreport glucose excursions. METHODS: Adult patients without (A) or with diabetes [non-insulin-treated type 2 (B), insulin-treated type 2 (C) or type 1 (D)] undergoing major surgery were monitored using CGM (Dexcom G6), with an electrochemical sensor in the interstitial fluid, during surgery and for up to 10 days postoperatively. Patients and health care staff were blinded to CGM values, and glucose management adhered to the standard diabetes care protocol. Thirty-day postoperative serious adverse events were recorded. The primary outcome was duration of hypoglycemia (glucose <70 mg/dL). Clinicaltrials.gov: NCT04473001. RESULTS: Seventy patients were included, with a median observation time of 4.0 days. CGM was recorded in median 96% of the observation time. The median daily duration of hypoglycemia was 2.5 minutes without significant difference between the 4 groups (A-D). Hypoglycemic events lasting ≥15 minutes occurred in 43% of all patients and 70% of patients with type 1 diabetes. Patients with type 1 diabetes spent a median of 40% of the monitoring time in the normoglycemic range 70 to 180 mg/dL and 27% in the hyperglycemic range >250 mg/dL. Duration of preceding hypo- and hyperglycemia tended to be longer in patients with serious adverse events, compared with patients without events, but these were exploratory analyses. CONCLUSIONS: Significant duration of both hypo- and hyperglycemia was detected in high proportions of patients, particularly in patients with diabetes, despite protocolized perioperative diabetes management.

Haemodynamic and respiratory perioperative outcomes for open versus robot-assisted radical cystectomy: A double-blinded, randomised trial.

BACKGROUND: The clinical impact of prolonged steep Trendelenburg position and CO2 pneumoperitoneum during robot-assisted radical cystectomy (RC) on intraoperative conditions and immediate postoperative recovery remains to be assessed. The current study investigates intraoperative and immediate postoperative outcomes for open RC (ORC) versus robot-assisted RC with intracorporal urinary diversion (iRARC) in a blinded randomised trial. We hypothesised that ORC would result in a faster haemodynamic and respiratory post-anaesthesia care unit (PACU) recovery compared to iRARC. METHODS: This study is a predefined sub-analysis of a single-centre, double-blinded, randomised feasibility study. Fifty bladder cancer patients were randomly assigned to ORC (n = 25) or iRARC (n = 25). Patients, PACU staff, and ward personnel were blinded to the surgical technique. Both randomisation arms followed the same anaesthesiologic procedure, fluid treatment plan, and PACU care. The primary outcome was immediate postoperative recovery using a standardised PACU Discharge Criteria (PACU-DC) score. Secondary outcomes included respiration- and arterial O2 saturation scores as well as perioperative interventions and recordings. RESULTS: All patients underwent the allocated treatment. The total PACU-DC score was highest 6 h postoperatively with no difference in the total score between randomisation arms (p = 0.80). Both the ORC and iRARC groups maintained a mean respiration- and arterial O2 saturation score below 1 (out of 3) throughout PACU stay. The iRARC patients had significantly, but clinically acceptable, higher maximum airway pressure and arterial blood pressure, as well as lower minimum pH levels. The ORC group received significantly more opioids after extubation but marginally less analgesics in the PACU, compared to the iRARC group. CONCLUSIONS: A prolonged Trendelenburg position and CO2 pneumoperitoneum was well-tolerated during iRARC, and immediate postoperative recovery was similar for ORC and iRARC patients.

Wireless Single-Lead versus Standard 12-Lead ECG, for ST-Segment Deviation during Adenosine Cardiac Stress Scintigraphy.

Wearable wireless electrocardiographic (ECG) monitoring is well-proven for arrythmia detection, but ischemia detection accuracy is not well-described. We aimed to assess the agreement of ST-segment deviation from single- versus 12-lead ECG and their accuracy for the detection of reversible ischemia. Bias and limits of agreement (LoA) were calculated between maximum deviations in ST segments from single- and 12-lead ECG during 82Rb PET-myocardial cardiac stress scintigraphy. Sensitivity and specificity for reversible anterior-lateral myocardial ischemia detection were assessed for both ECG methods, using perfusion imaging results as a reference. Out of 110 patients included, 93 were analyzed. The maximum difference between single- and 12-lead ECG was seen in II (-0.019 mV). The widest LoA was seen in V5, with an upper LoA of 0.145 mV (0.118 to 0.172) and a lower LoA of -0.155 mV (-0.182 to -0.128). Ischemia was seen in 24 patients. Single-lead and 12-lead ECG both had poor accuracy for the detection of reversible anterolateral ischemia during the test: single-lead ECG had a sensitivity of 8.3% (1.0-27.0%) and specificity of 89.9% (80.2-95.8%), and 12-lead ECG a sensitivity of 12.5% (3.0-34.4%) and a specificity of 91.3% (82.0-96.7%). In conclusion, agreement was within predefined acceptable criteria for ST deviations, and both methods had high specificity but poor sensitivity for the detection of anterolateral reversible ischemia. Additional studies must confirm these results and their clinical relevance, especially in the light of the poor sensitivity for detecting reversible anterolateral cardiac ischemia.

The impact of continuous wireless monitoring on adverse device effects in medical and surgical wards: a review of current evidence.

Novel technologies allow continuous wireless monitoring systems (CWMS) to measure vital signs and these systems might be favorable compared to intermittent monitoring regarding improving outcomes. However, device safety needs to be validated because uncertain evidence challenges the clinical implementation of CWMS. This review investigates the frequency of device-related adverse events in patients monitored with CWMS in general hospital wards. Systematic literature searches were conducted in PubMed and Embase. We included trials of adult patients in general hospital wards monitored with CWMS. Our primary outcome was the frequency of unanticipated serious adverse device effects (USADEs). Secondary outcomes were adverse device effects (ADEs) and serious adverse device effects (SADE). Data were extracted from eligible studies and descriptive statistics were applied to analyze the data. Seven studies were eligible for inclusion with a total of 1485 patients monitored by CWMS. Of these patients, 54 patients experienced ADEs (3.6%, 95% CI 2.8-4.7%) and no USADEs or SADEs were reported (0%, 95% CI 0-0.31%). The studies of the SensiumVitals® patch, the iThermonitor, and the ViSi Mobile® device reported 28 (9%), 25 (5%), and 1 (3%) ADEs, respectively. No ADEs were reported using the HealthPatch, WARD 24/7 system, or Coviden Alarm Management. Current evidence suggests that CWMS are safe to use but systematic reporting of all adverse device effects is warranted.

Associations between clinical interventions and transcutaneous blood gas values in postoperative patients.

PURPOSE: Postoperative monitoring of circulation and respiration is pivotal to guide intervention strategies and ensure patient outcomes. Transcutaneous blood gas monitoring (TCM) may allow for noninvasive assessment of changes in cardiopulmonary function after surgery, including a more direct assessment of local micro-perfusion and metabolism. To form the basis for studies assessing the clinical impact of TCM complication detection and goal-directed-therapy, we examined the association between clinical interventions in the postoperative period and changes in transcutaneous blood gasses. METHODS: Two-hundred adult patients who have had major surgery were enrolled prospectively and monitored with transcutaneous blood gas measurements (oxygen (TcPO2) and carbon dioxide (TcPCO2)) for 2 h in the post anaesthesia care unit, with recording of all clinical interventions. The primary outcome was changes in TcPO2, secondarily TcPCO2, from 5 min before a clinical intervention versus 5 min after, analysed with paired t-test. RESULTS: Data from 190 patients with 686 interventions were analysed. During clinical interventions, a mean change in TcPO2 of 0.99 mmHg (95% CI-1.79-0.2, p = 0.015) and TcPCO2 of-0.67 mmHg (95% CI 0.36-0.98, p < 0.001) was detected. CONCLUSION: Clinical interventions resulted in significant changes in transcutaneous oxygen and carbon dioxide. These findings suggest future studies to assess the clinical value of changes in transcutaneous PO2 and PCO2 in a postoperative setting. TRIAL REGISTRY: Clinical trial number: NCT04735380. CLINICAL TRIAL REGISTRY: https://clinicaltrials.gov/ct2/show/NCT04735380.

Quantifying physiological stability in the general ward using continuous vital signs monitoring: the circadian kernel density estimator.

Technological advances seen in recent years have introduced the possibility of changing the way hospitalized patients are monitored by abolishing the traditional track-and-trigger systems and implementing continuous monitoring using wearable biosensors. However, this new monitoring paradigm raise demand for novel ways of analyzing the data streams in real time. The aim of this study was to design a stability index using kernel density estimation (KDE) fitted to observations of physiological stability incorporating the patients' circadian rhythm. Continuous vital sign data was obtained from two observational studies with 491 postoperative patients and 200 patients with acute exacerbation of chronic obstructive pulmonary disease. We defined physiological stability as the last 24 h prior to discharge. We evaluated the model against periods of eight hours prior to events defined either as severe adverse events (SAE) or as a total score in the early warning score (EWS) protocol of ≥ 6, ≥ 8, or ≥ 10. The results found good discriminative properties between stable physiology and EWS-events (area under the receiver operating characteristics curve (AUROC): 0.772-0.993), but lower for the SAEs (AUROC: 0.594-0.611). The time of early warning for the EWS events were 2.8-5.5 h and 2.5 h for the SAEs. The results showed that for severe deviations in the vital signs, the circadian KDE model can alert multiple hours prior to deviations being noticed by the staff. Furthermore, the model shows good generalizability to another cohort and could be a simple way of continuously assessing patient deterioration in the general ward.

The future of postoperative vital sign monitoring in general wards: improving patient safety through continuous artificial intelligence-enabled alert formation and reduction.

PURPOSE: Monitoring of vital signs at the general ward with continuous assessments aided by artificial intelligence (AI) is increasingly being explored in the clinical setting. This review aims to describe current evidence for continuous vital sign monitoring (CVSM) with AI-based alerts - from sensor technology, through alert reduction, impact on complications, and to user-experience during implementation. RECENT FINDINGS: CVSM identifies significantly more vital sign deviations than manual intermittent monitoring. This results in high alert generation without AI-evaluation, both in patients with and without complications. Current AI is at the rule-based level, and this potentially reduces irrelevant alerts and identifies patients at need. AI-aided CVSM identifies complications earlier with reduced staff workload and a potential reduction of severe complications. SUMMARY: The current evidence for AI-aided CSVM suggest a significant role for the technology in reducing the constant 10-30% in-hospital risk of severe postoperative complications. However, large, randomized trials documenting the benefit for patient improvements are still sparse. And the clinical uptake of explainable AI to improve implementation needs investigation.

Hyperoxia and Antioxidants for Myocardial Injury in Noncardiac Surgery: A 2 × 2 Factorial, Blinded, Randomized Clinical Trial.

BACKGROUND: Hyperoxia and oxidative stress may be associated with increased risk of myocardial injury. The authors hypothesized that a perioperative inspiratory oxygen fraction of 0.80 versus 0.30 would increase the degree of myocardial injury within the first 3 days of surgery, and that an antioxidant intervention would reduce degree of myocardial injury versus placebo. METHODS: A 2 × 2 factorial, randomized, blinded, multicenter trial enrolled patients older than 45 yr who had cardiovascular risk factors undergoing major noncardiac surgery. Factorial randomization allocated patients to one of two oxygen interventions from intubation and at 2 h after surgery, as well as antioxidant intervention or matching placebo. Antioxidants were 3 g IV vitamin C and 100 mg/kg N-acetylcysteine. The primary outcome was the degree of myocardial injury assessed by the area under the curve for high-sensitive troponin within the first 3 postoperative days. RESULTS: The authors randomized 600 participants from April 2018 to January 2020 and analyzed 576 patients for the primary outcome. Baseline and intraoperative characteristics did not differ between groups. The primary outcome was 35 ng · day/l (19 to 58) in the 80% oxygen group; 35 ng · day/l (17 to 56) in the 30% oxygen group; 35 ng · day/l (19 to 54) in the antioxidants group; and 33 ng · day/l (18 to 57) in the placebo group. The median difference between oxygen groups was 1.5 ng · day/l (95% CI, -2.5 to 5.3; P = 0.202) and -0.5 ng · day/l (95% CI, -4.5 to 3.0; P = 0.228) between antioxidant groups. Mortality at 30 days occurred in 9 of 576 patients (1.6%; odds ratio, 2.01 [95% CI, 0.50 to 8.1]; P = 0.329 for the 80% vs. 30% oxygen groups; and odds ratio, 0.79 [95% CI, 0.214 to 2.99]; P = 0.732 for the antioxidants vs. placebo groups). CONCLUSIONS: Perioperative interventions with high inspiratory oxygen fraction and antioxidants did not change the degree of myocardial injury within the first 3 days of surgery. This implies safety with 80% oxygen and no cardiovascular benefits of vitamin C and N-acetylcysteine in major noncardiac surgery.

Open vs robot-assisted radical cystectomy (BORARC): a double-blinded, randomised feasibility study.

OBJECTIVE: To examine surgical outcomes and feasibility of blinding patients and care providers to the surgical technique of radical cystectomy (RC). PATIENTS AND METHODS: Single-centre, parallel-group, double-blinded, randomised feasibility study of open RC (ORC) vs robot-assisted RC with intracorporeal urinary diversion (iRARC) in an 'Enhanced Recovery After Surgery' setup. A total of 50 patients aged ≥18 years with bladder cancer planned for RC with an ileal conduit were included. Patients with previous major abdominal/pelvic surgery, pelvic radiation or anaesthesiological contraindications were excluded. Primary outcomes were proportion of unblinded patients and success of blinding using Bang's Blinding Index. Secondary outcomes included length of stay (LOS), complication rates, blood loss, pain, and opioid consumption. RESULTS: A total of 26% of the patients were unblinded before discharge. We demonstrated that patients and doctors remained blinded for the allocated treatment, but nurses did not. Blood loss was greater in the ORC group as was operative time in the iRARC group. We found no difference in complication rate, LOS, or use of analgesics. CONCLUSIONS: The present study demonstrates that blinding of surgical technique in RC is possible. The results of secondary outcomes are consistent with the findings of previous unblinded randomised controlled trials. Our study highlights that it is possible to perform a blinded phase III study to explore the optimal surgical technique in RC.

Wireless Single-Lead ECG Monitoring to Detect New-Onset Postoperative Atrial Fibrillation in Patients After Major Noncardiac Surgery: A Prospective Observational Study.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is associated with several cardiovascular complications and higher mortality. Several pathophysiological processes such as hypoxia can trigger POAF, but these are sparsely elucidated, and POAF is often asymptomatic. In patients undergoing major gastrointestinal cancer surgery, we aimed to describe the frequency of POAF as automatically estimated and detected via wireless repeated sampling monitoring and secondarily to describe the association between preceding vital sign deviations and POAF. METHOD: Patients ≥60 years of age undergoing major gastrointestinal cancer surgery were continuously monitored for up to 4 days postoperatively. Electrocardiograms were obtained every minute throughout the monitoring period. Clinical staff were blinded to all measurements. As for the primary outcome, POAF was defined as 30 consecutive minutes or more detected by a purpose-built computerized algorithm and validated by cardiologists. The primary exposure variable was any episode of peripheral oxygen saturation (Spo2) <85% for >5 consecutive minutes before POAF. RESULTS: A total of 30,145 hours of monitoring was performed in 398 patients, with a median of 92 hours per patient (interquartile range [IQR], 54-96). POAF was detected in 26 patients (6.5%; 95% confidence interval [CI], 4.5-9.4) compared with 14 (3.5%; 95% CI, 1.94-5.83) discovered by clinical staff in the monitoring period. POAF was followed by 9.4 days hospitalization (IQR, 6.5-16) versus 6.5 days (IQR, 2.5-11) in patients without POAF. Preceding episodes of Spo2 <85% for >5 minutes (OR, 1.02; 95% CI, 0.24-4.00; P = .98) or other vital sign deviations were not significantly associated with POAF. CONCLUSIONS: New-onset POAF occurred in 6.5% (95% CI, 4.5-9.4) of patients after major gastrointestinal cancer surgery, and 1 in 3 cases was not detected by the clinical staff (35%; 95% CI, 17-56). POAF was not preceded by vital sign deviations.

Continuously monitored vital signs for detection of myocardial injury in high-risk patients - An observational study.

BACKGROUND: Patients are at risk of myocardial injury after major non-cardiac surgery and during acute illness. Myocardial injury is associated with mortality, but often asymptomatic and currently detected through intermittent cardiac biomarker screening. This delays diagnosis, where vital signs deviations may serve as a proxy for early signs of myocardial injury. This study aimed to assess the association between continuous monitored vital sign deviations and subsequent myocardial injury following major abdominal cancer surgery and during acute exacerbation of chronic obstructive pulmonary disease. METHODS: Patients undergoing major abdominal cancer surgery or admitted with acute exacerbation of chronic obstructive pulmonary disease had daily troponin measurements. Continuous wireless monitoring of several vital signs was performed for up to 96 h after admission or surgery. The primary exposure was cumulative duration of peripheral oxygen saturation (SpO2 ) below 85% in the 24 h before the primary outcome of myocardial injury, defined as a new onset ischaemic troponin elevation assessed daily. If no myocardial injury occurred, the primary exposure was based on the first 24 h of measurement. RESULTS: A total of 662 patients were continuously monitored and 113 (17%) had a myocardial injury. Cumulative duration of SpO2  < 85% was significantly associated with myocardial injury (mean difference 14.2 min [95% confidence interval -4.7 to 33.1 min]; p = .005). Durations of hypoxaemia (SpO2  < 88% and SpO2  < 80%), tachycardia (HR > 110 bpm and HR > 130 bpm) and tachypnoea (RR > 24 min-1 and RR > 30 min-1 ) were also significantly associated with myocardial injury (p < .04, for all). CONCLUSION: Duration of severely low SpO2 detected by continuous wireless monitoring is significantly associated with myocardial injury in high-risk patients admitted to hospital wards. The effect of early detection and interventions should be assessed next.

Continuous monitoring of vital sign abnormalities; association to clinical complications in 500 postoperative patients.

BACKGROUND: Patients undergoing major surgery are at risk of complications, so-called serious adverse events (SAE). Continuous monitoring may detect deteriorating patients by recording abnormal vital signs. We aimed to assess the association between abnormal vital signs inspired by Early Warning Score thresholds and subsequent SAEs in patients undergoing major abdominal surgery. METHODS: Prospective observational cohort study continuously monitoring heart rate, respiratory rate, peripheral oxygen saturation, and blood pressure for up to 96 h in 500 postoperative patients admitted to the general ward. Exposure variables were vital sign abnormalities, primary outcome was any serious adverse event occurring within 30 postoperative days. The primary analysis investigated the association between exposure variables per 24 h and subsequent serious adverse events. RESULTS: Serious adverse events occurred in 37% of patients, with 38% occurring during monitoring. Among patients with SAE during monitoring, the median duration of vital sign abnormalities was 272 min (IQR 110-447), compared to 259 min (IQR 153-394) in patients with SAE after monitoring and 261 min (IQR 132-468) in the patients without any SAE (p = .62 for all three group comparisons). Episodes of heart rate ≥110 bpm occurred in 16%, 7.1%, and 3.9% of patients in the time before SAE during monitoring, after monitoring, and without SAE, respectively (p < .002). Patients with SAE after monitoring experienced more episodes of hypotension ≤90 mm Hg/24 h (p = .001). CONCLUSION: Overall duration of vital sign abnormalities at current thresholds were not significantly associated with subsequent serious adverse events, but more patients with tachycardia and hypotension had subsequent serious adverse events. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT03491137.

Machine learning classifiers do not improve prediction of hospitalization > 2 days after fast-track hip and knee arthroplasty compared with a classical statistical risk model.

Background and purpose: Prediction of postoperative outcomes and length of hospital stay (LOS) of patients is vital for allocation of healthcare resources. We investigated the performance of prediction models based on machinelearning algorithms compared with a previous risk stratification model using traditional multiple logistic regression, for predicting the risk of a LOS of > 2 days after fast-track total hip and knee replacement. Patients and methods: 3 different machine learning classifiers were trained on data from the Lundbeck Centre for Fast-track Hip and Knee Replacement Database (LCDB) collected from 9,512 patients between 2016 and 2017. The chosen classifiers were a random forest classifier (RF), a support vector machine classifier with a polynomial kernel (SVM), and a multinomial Naïve-Bayes classifier (NB). Results: Comparing performance measures of the classifiers with the traditional model revealed that all the models had a similar performance in terms of F1 score, accuracy, sensitivity, specificity, area under the receiver operating curve (AUC), and area under the precision-recall curve (AUPRC). A feature importance analysis of the RF classifier found hospital, age, use of walking aid, living alone, and joint operated on to be the most relevant input features. None of the classifiers reached a clinically relevant performance with the input data from the LCDB. Interpretation: Despite the promising prospects of machine-learning practices for disease and risk prediction, none of the machine learning models tested outperformed the traditional multiple regression model in predicting which patients in this cohort had a LOS > 2 days.

Phrenic nerve block on severe post-hepatectomy shoulder pain: A randomized, double-blind, placebo-controlled, pilot study.

BACKGROUND: Severe shoulder pain occurs frequently after surgery close to the diaphragm, potentially caused by referred pain via the ipsilateral phrenic nerve. We aimed to assess the analgesic effect of an ultrasound-guided phrenic nerve block on moderate to severe right-sided shoulder pain after open partial hepatectomy. METHODS: This was a randomized, double-blind, placebo-controlled, pilot study, comparing ultrasound-guided phrenic nerve block (ropivacaine 0.75 mg/mL) versus placebo (isotonic sodium chloride 0.9 mg/mL) on severe post-hepatectomy shoulder pain (NRS ≥6). Pre- and postoperative spirometry and arterial blood gas analyses were used to assess respiratory function. Subjects with chronic lung disease were excluded. Unfortunately, due to lack of funding, the trial was ended prematurely and therefore presented as a pilot study. RESULTS: One hundred and one subjects were screened for eligibility; 14 subjects were randomized, and two subjects were later excluded; thus, 12 subjects were analyzed with six in each group. A statistically significant difference in reduction in median pain intensity between groups was observed 15 minutes after phrenic nerve block ("ropivacaine first" ΔNRS: -6.0 [-6.0 to -3.0] vs. "saline first" ΔNRS: 0 [-6.0 to 1.0], P = .026). Spirometry results and arterial blood gas analyses were not clinically impacted by the block. CONCLUSIONS: Postoperative phrenic nerve block significantly reduced severe post-hepatectomy shoulder pain. Larger studies are warranted to confirm the lack of clinically relevant block-related impairment of respiratory function.

Continuous peripheral perfusion index in patients admitted to hospital wards - An observational study.

INTRODUCTION: Risk patients admitted to hospital wards may quickly develop haemodynamic deterioration and early recognition has high priority to allow preventive intervention. The peripheral perfusion index (PPI) may be an indicator of circulatory distress by assessing peripheral perfusion non-invasively from photoplethysmography. We aimed to describe the characteristics of PPI in hospitalized patients since this is not well-studied. MATERIALS AND METHODS: Patients admitted due to either acute exacerbation of chronic obstructive pulmonary disease (AECOPD) or after major abdominal cancer surgery were included in this study. Patients were monitored continuously up to 96 hours with a pulse oximeter. Comparisons between median PPI each day, time of day and admission type were described with mean difference (MD) and were analysed using Wilcoxon rank sum test and related to morbidity and mortality. RESULTS: PPI data from 291 patients were recorded for a total of 9279 hours. Median PPI fell from 1.4 (inter quartile range, IQR 0.9-2.3) on day 1 to 1.0 (IQR 0.6-1.6) on day 4. Significant differences occurred between PPI day vs evening (MD = 0.18, 95% CI 0.16-0.20, P = .028), day vs night (MD = 0.56, 95% CI 0.49-0.62, P < .0001) and evening vs night (MD = 0.38, 95% CI 0.33-0.42, P = .002). No significant difference in median PPI between AECOPD and surgical patients was found (MD = 0.15, 95% CI -0.08-0.38, P = .62). CONCLUSION: Lower PPI during daytime vs evening and night-time were seen for both populations. The highest frequency of serious adverse events and mortality was seen among patients with low median PPI. The clinical impact of PPI monitoring needs further confirmation.

Preoperative TruCulture® whole blood cytokine response predicts post-operative inflammation in pancreaticoduodenectomy patients-A pilot cohort study.

Major surgery is associated with substantial morbidity and mortality with early post-operative adverse events (POAE) occurring in 30% of patients within the first 30 days. The underlying pathogenesis is multifactorial, including immune dysfunction and increased inflammatory response to surgery. We investigated preoperative immune function by the TruCulture® whole blood technique in a cohort of patients undergoing pancreaticoduodenectomy (PD), hypothesizing that patients developing inflammatory POAE defined as leucocytosis, fever or high (above median) area under the curve (AUC) C-reactive protein (CRP) the first post-operative week would display perturbed preoperative immune function. Sixty-two adult patients were screened, 30 included and 11 excluded post-inclusion due to other surgical procedures than PD and post-operative complications directly attributed to surgery, leaving 19 patients for analysis of preoperative immune function. Patients developing leucocytosis (n = 5, 26%) had lower Toll-like receptor (TLR)-3-stimulated IL-12p40 and higher Candida Albicans (TLR1/2/4/6, Dectin-1)-stimulated TNF-α, compared to patients without leucocytosis (all P < .05). Patients developing fever (n = 7, 37%) had lower TLR7/8-stimulated IFN-γ and patients with high AUC CRP (n = 9, 47%) had lower TLR3-stimulated IFN-γ and IL-6 and lower TLR7/8-stimulated IL-10 (all P < .05), compared to patients without fever or low CRP, respectively. In conclusion, patients with inflammatory POAE displayed lower preoperative stimulated IL-12p40, IFN-γ, IL-6 and IL-10 and higher TNF-α response, compared to patients without inflammatory POAE. This finding suggests that TruCulture is a feasible immunologic screening tool in surgical patients, with a potential for preoperative identification of patients at increased risk for inflammatory POAE, allowing for risk-based intervention trials.

Effects of post-operative furosemide in adult surgical patients: A systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: Acute kidney injury (AKI) is associated with increased morbidity and mortality and may present as oliguria in the post-operative phase. Diuretics, including furosemide, are commonly used in post-operative patients. Accordingly, we aimed to assess the balance between benefits and harms of furosemide post-operatively in adult surgical patients. METHODS: We conducted a systematic review with meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements, the Cochrane Handbook and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. We included randomised clinical trials (RCTs) comparing post-operative treatment with furosemide vs no furosemide in adult surgical patients. Risk ratios (RR) with 95% confidence intervals (CI) were estimated by conventional meta-analysis and trial sequential analysis (TSA). RESULTS: Two thousand five hundred and sixty seven records were identified and four trials with 325 patients in total were included. All were adjudicated as having overall high risk of bias. We observed no statistically significant difference between furosemide- vs no furosemide-treated patients in any of the predefined outcome measures, including AKI (RR 1.07, 95% CI 0.43-2.65), all-cause mortality (RR 1.73, 95% CI 0.62-4.80, use of vasopressors post-operatively (RR 1.04, 95% CI 0.74-1.44) or need for renal replacement therapy (RR 3.87, 95% CI 0.44-33.99). TSA highlighted sparse data, and the overall quality of evidence was very low. CONCLUSION: In this systematic review, we found that the quantity and quality of evidence for using furosemide post-operatively in adult surgical patients were very low with no firm evidence for benefit or harm.

Persistent severe post-operative hypotension after pancreaticoduodenectomy is related to increased inflammatory response.

BACKGROUND: Hypotension during major surgery is frequent, resulting in increased need for observation in the post-anaesthesia care unit and treatment including vasopressors and fluids. However, although severe hypotension in the immediate post-operative recovery phase after major surgery is suggested to be related to increased morbidity and mortality, the underlying risk factors are not well described, hindering advancements in prevention and treatment. METHODS: We performed a retrospective study assessing factors (age, gender, body-mass index, cardiac co-morbidity, haemoglobin, absolute and increase in c-reactive protein on the first post-operative day, bleeding, fluid balance at the end of surgery and the first post-operative day) related to severe persistent hypotension (SPH) (SPH: need for noradrenaline to maintain a mean arterial blood pressure (MAP) >65.0 mm Hg on the morning after surgery) and occurrence of other early (24 hours) complications. One hundred patients undergoing pancreaticoduodenectomy (PD) with pre-operative high-dose glucocorticoid and goal-directed fluid therapy were enrolled and perioperative data collected from anaesthetic and medical records. RESULTS: Forty-five patients had SPH, who had a significantly higher increase in CRP levels the morning after surgery (median 50 mg L-1 vs 41 mg L-1 , SPH vs non-SPH, respectively, P = .028), and a significantly more positive fluid balance at discharge (median 1457 ml vs 1031 ml, respectively, P = .027) vs patients without SPH. CONCLUSIONS: Severe persistent hypotension after PD was associated with significantly increased inflammatory response and increased need for fluids. Future studies should investigate the effect of further inflammatory control in PD to improve haemodynamics and morbidity.