Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE): a randomized multicentre feasibility trial.

BACKGROUND/PURPOSE: Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care. METHODS: Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion. RESULTS: Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960-8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804-12,401) in the control group (n = 48); corresponding to a Hodges-Lehmann median difference of 3560 ml [95% confidence interval 1614-5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation. CONCLUSION: Protocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088.

Bypassing the post-anaesthesia care unit after elective hip and knee arthroplasty: a prospective cohort safety study.

Following knee and hip arthroplasty, transfer to a recovery area immediately following surgery and before going to ward might be unnecessary in low-risk patients. Avoiding the recovery area in this way could allow for more targeted use of resources for higher risk patients, which may improve operating theatre flow and productivity. A prospective single-centre cohort study on the safety of criteria for bypassing the post-anaesthesia care unit in elective hip and knee arthroplasty was designed. Criteria were: ASA physical status < 3; peri-operative bleeding < 500 ml; low postoperative discharge-score (modified Aldrete-score); and an uncomplicated surgical and neuraxial anaesthesia procedure. The primary outcome was the number of patients in need of secondary readmission to the post-anaesthesia care unit. Events within the first 24 postoperative hours were recorded, along with readmission and complication rates. A total of 696 patients were included, with 287 (41%) undergoing total hip arthroplasty, 274 (39%) undergoing total knee arthroplasty and 135 (19%) undergoing unicompartmental knee-arthroplasty. Of these, 207 (44%) bypassed the post-anaesthesia care unit. Patients all received multimodal analgesia without peripheral nerve blockade. Only one patient in the ward group required secondary readmission to the post-anaesthesia care unit. Within 24 h, 151 events were reported, with 41 (27%) in the ward group and 110 (73%) in the post-anaesthesia care unit group. Two events in each group occurred within 2 hours of surgery. No complications were attributed to bypassing the post-anaesthesia care unit. The use of simple pragmatic criteria for bypassing the post-anaesthesia care unit for patients undergoing knee and hip arthroplasty with spinal anaesthesia is possible and associated with significant reduction of post-anaesthesia care unit admission and without apparent safety issues. Confirmation is needed from other studies and external validity should be interpreted cautiously in centres with different peri-operative regimens, organisational and staffing structures.

High-digestible silages allow low concentrate supply without affecting milk production or methane emissions.

In this study, we tested a response function comprising responses in milk to changes in organic matter digestibility of silages and concentrate supply. We studied the effect of changes in silage digestibility and concentrate supply on milk yield, feed intake, body weight, and methane production using 60 Norwegian Red cows. The experiment was a complete randomized block design comprising 3 periods. The pre-experimental period lasted 20 d and all the cows were fed a common silage for ad libitum intake and concentrate according to yield. Next, response period 1 lasted 17 d and the cows were divided into 2 treatments, where a low-digestible silage (LDS) was fed to half of the cows, and the other half were fed a high-digestible silage (HDS). Both groups were fed silage for ad libitum silage intake. Concentrate was optimized according to the yield and type of silage offered. In this period, the effect of silage was evaluated using a mixed model, including the results from pre-experimental period, with parity as a covariate and animal as a random effect. In response period 2, which lasted 20 d, the concentrate level was evaluated by dividing the silage digestibility treatments further into 3 subgroups. Concentrate was increased by 2 kg of dry matter (DM) per day, decreased by 2 kg of DM/d, or remained unchanged. In response period 1, silage treatments were optimized to obtain similar yields and resulted in a lower concentrate offer to HDS treatment. However, the HDS treatment showed a 3.0 kg of DM/d higher total feed intake due to a higher than expected silage intake. This resulted in 3.5 kg higher energy-corrected milk (ECM). Methane emissions were similar between silage treatments, but HDS showed lower methane per kilogram of DM due to its higher intake. The effect of concentrate supply level and interaction with silage digestibility was evaluated using mixed models, including the results for response period 1, with parity as a covariate and animal as a random effect. The reduction in concentrate offer by 2 kg/d in response period 2 was compensated for by increased 1.3 kg of DM/d of silage intake for HDS, resulting in similar intake (22.1 kg of DM/d and 21.7 kg of DM/d without and with concentrate reduction, respectively) and ECM yields (29.4 and 29 kg of ECM without and with concentrate reduction, respectively). However, concentrate offer reduction could not be compensated for by increased silage intake for LDS and resulted in lower milk yields (27.5 kg of ECM). Increased concentrate showed a higher marginal ECM response (kg of ECM per kg of additional concentrate intake) for LDS (1.8 vs. 3.3 kg of ECM for HDS and LDS, respectively). Thus, the drop in milk yields could be compensated for by increased concentrate offers if LDS are fed. Total methane production increased with increased concentrate intake, regardless of silage digestibility. Methane emissions per unit of milk were affected by total DM intake rather than by changes in silage digestibility and concentrate level. The results of this study are based on short-term periods and could show differences if study periods were longer; the results should be interpreted accordingly.

Postoperative complications and waiting time for surgical intervention after radiologically guided drainage of intra-abdominal abscess in patients with Crohn's disease.

BACKGROUND: In patients with active Crohn's disease (CD), treatment of intra-abdominal abscess usually comprises antibiotics and radiologically guided percutaneous drainage (PD) preceding surgery. The aim of this study was to investigate the risk of postoperative complications and identify the optimal time interval for surgical intervention after PD. METHODS: A multicentre, international, retrospective cohort study was carried out. Details of patients with diagnosis of CD who underwent ultrasonography- or CT-guided PD were retrieved from hospital records using international classification of disease (ICD-10) diagnosis code for CD combined with procedure code for PD. Clinical variables were retrieved and the following outcomes were measured: 30-day postoperative overall complications, intra-abdominal septic complications, unplanned intraoperative adverse events, surgical-site infections, sepsis and pathological postoperative ileus, in addition to abscess recurrence. Patients were categorized into three groups according to the length of the interval from PD to surgery (1-14 days, 15-30 days and more than 30 days) for comparison of outcomes. RESULTS: The cohort comprised 335 CD patients with PD followed by surgery. Median age was 33 (i.q.r. 24-44) years, 152 (45.4 per cent) were females, and median disease duration was 9 (i.q.r. 3.6-15) years. Overall, the 30-day postoperative complications rate was 32.2 per cent and the mortality rate was 1.5 per cent. After adjustment for co-variables, older age (odds ratio 1.03 (95 per cent c.i. 1.01 to 1.06), P < 0.012), residual abscess after PD (odds ratio 0.374 (95 per cent c.i. 0.19 to 0.74), P < 0.014), smoking (odds ratio 1.89 (95 per cent c.i. 1.01 to 3.53), P = 0.049) and low serum albumin concentration (odds ratio 0.921 (95 per cent c.i. 0.89 to 0.96), P < 0.001) were associated with higher rates of postoperative complications. A short waiting interval, less than 2 weeks after PD, was associated with a high incidence of abscess recurrence (odds ratio 0.59 (95 per cent c.i. 0.36 to 0.96), P = 0.042). CONCLUSION: Smoking, low serum albumin concentration and older age were significantly associated with postoperative complications. An interval of at least 2 weeks after successful PD correlated with reduced risk of abscess recurrence.

A static model for estimating energy content of compound feeds in a dynamic feed evaluation system.

The objective of the study was to develop a static empirical model for the estimation of net energy content of compound feeds in a dynamic feeding system using net energy for lactation at 20 kg of dry matter intake/d (NEL20) values calculated by the Nordic Feed Evaluation System (NorFor) model. In the NorFor system, NEL20 is a standardized value used to describe net energy content of feeds. The static model would allow prediction of the net energy value of compound feeds without access to the input data needed for the dynamic models. Our hypothesis was that NEL20 values of compound feeds can be predicted using organic matter digestibility (in vitro) and chemical components of the compound feeds as input variables. For this, 75 compound feeds and their 108 associated ingredients were collected across Scandinavia for model development. The proposed best model for prediction of compound feed NEL20 included crude fat, neutral detergent fiber, digestible organic matter measured in vitro, and crude protein (urea corrected) as independent variables. Lack of additivity of chemical components between values analyzed directly in the compound feed and values calculated by the weighted sum of ingredients was detected as the main source of error in the model, emphasizing the importance of accurate chemical analysis and sampling practices. Results from practical use of the model show that it may be a valuable tool that could be used by several actors in the feeding sector using the NorFor system. Feed manufacturers could use it to monitor the net energy content in their final product, and farmers could use it to check the net energy content of the purchased compound feed. However, validation of this model against an independent set of samples is lacking in this study and its prediction performance should be further evaluated. The model will need recalibration if the feed parameters used in the dynamic model for the estimation of reference values change, as this would not be reflected in the predicted values of the created model.

The impact of rising sea temperatures on an Arctic top predator, the narwhal.

Arctic top predators are expected to be impacted by increasing temperatures associated with climate change, but the relationship between increasing sea temperatures and population dynamics of Arctic cetaceans remains largely unexplored. Narwhals (Monodon monoceros) are considered to be among the most sensitive of Arctic endemic marine mammals to climate change due to their limited prey selection, strict migratory patterns and high site fidelity. In the context of climate change, we assume that the population dynamics of narwhals are partly influenced by changes in environmental conditions, with warm areas of increasing sea temperatures having lower abundance of narwhals. Using a unique large dataset of 144 satellite tracked narwhals, sea surface temperature (SST) data spanning 25 years (1993-2018) and narwhal abundance estimates from 17 localities, we (1) assessed the thermal exposure of this species, (2) investigated the SST trends at the summer foraging grounds, and (3) assessed the relationship between SST and abundance of narwhals. We showed a sharp SST increase in Northwest, Mideast and Southeast Greenland, whereas no change could be detected in the Canadian Arctic Archipelago (CAA) and in the Greenland Sea. The rising sea temperatures were correlated with the smallest narwhal abundance observed in the Mideast and Southeast Greenland (< 2000 individuals), where the mean summer sea temperatures were the highest (6.3 °C) compared to the cold waters of the CAA (0.7 °C) that were associated with the largest narwhal populations (> 40,000 individuals). These results support the hypothesis that warming ocean waters will restrict the habitat range of the narwhal, further suggesting that narwhals from Mideast and Southeast Greenland may be under pressure to abandon their traditional habitats due to ocean warming, and consequently either migrate further North or locally go extinct.

Precision and additivity of organic matter digestibility obtained via in vitro multi-enzymatic method.

The enzymatic digestibility of organic matter (EDOM) method is an in vitro multi-enzymatic method for estimating the organic matter (OM) digestibility of feeds. The EDOM method previously showed high accuracy with in vivo values for compound feeds. The aim of this study was to evaluate the precision of the EDOM method and determine its additivity, compared with the long-assumed additive property of the chemical components of compound feeds. 149 feed samples, 70 commercial compound feeds and 79 associated ingredients, were analyzed in a laboratory (lab1) for OM digestibility measured by EDOM (OMDEDOM) with 2 repetitions separated in time to estimate repeatability. Of the total samples, 49 compound feeds were further analyzed in a commercial laboratory (lab2) for OMDEDOM to determine reproducibility. The 49 compounds and their 69 associated ingredients were also analyzed by lab2 for dry matter (DM), ash, crude protein (CP), neutral detergent fiber (NDF), and starch. The EDOM method resulted in an intralaboratory correlation of 98.9% and an interlaboratory correlation of 92.6%, with no significant mean bias between the 2 laboratories tested. The formulation of compound feeds, total mixed rations, and mixtures in general assumes that their nutrient content can be calculated by adding together the nutrient supply of individual ingredients. This is of great importance in the feed industry for the creation of compound feeds. Additivity of OMDEDOM for the compound feed samples was evaluated by comparing the sum of the digestible OM (DOMEDOM) of the ingredients (predicted) with DOMEDOM estimated directly in the compound feed (observed). The regression of predicted versus observed showed a coefficient of determination (R2) of 0.93 and root mean square error (RMSE) of 1.07% of total DM, with no linear bias but with a mean bias (0.83% of DM). Additivity of CP, starch, crude fat, and NDF showed an R2 of 0.95, 0.98, 0.95, and 0.93, and RMSE of 1.56, 1.90, 0.39, and 1.46% of DM, respectively, all presenting linear bias. Crude fat also presented mean bias. Although significant, all linear and mean bias for DOMEDOM and chemical components were within the acceptable error limits for declaration of feeds. The results demonstrate the high precision of the EDOM method and its additive property, which is an advantage for the estimation of OM digestibility in compound feeds. Moreover, results of the tests of chemical components confirm their additive property.

Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial.

NeoRes I is a randomized phase II trial comparing neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy in the treatment of resectable cancer of the esophagus or gastroesophageal junction. Patients with biopsy-proven adenocarcinoma or squamous cell carcinoma, T1N1 or T2-3N0-1 and M0-M1a (AJCC 6th ed.), were randomized to receive three 3-weekly cycles of cisplatin 100 mg/m2 day 1 and fluorouracil 750 mg/m2/24 hours, days 1-5 with or without the addition of concurrent radiotherapy 40 Gy, 2 Gy/fraction, 5 days a week, followed by esophageal resection with two-field lymphadenectomy. Primary endpoint was complete histopathological response rate in the primary tumor. Survival and recurrence patterns were evaluated as secondary endpoints. Between 2006 and 2013, 181 patients were enrolled in Sweden and Norway. All three chemotherapy cycles were delivered to 73% of the patients allocated to chemoradiotherapy and to 86% of the patients allocated to chemotherapy. 87% of those allocated to chemoradiotherapy received full dose radiotherapy. 87% in the chemoradiotherapy group and 86% in the chemotherapy group underwent tumor resection. Initial results showed that patients allocated to chemoradiotherapy more often responded with complete histopathological response in the primary tumor (28% vs. 9%). Treatment-related complications were similar between the groups although postoperative complications were more severe in the chemoradiotherapy group. This article reports the long-term results. Five-year progression-free survival was 38.9% (95% CI 28.9%-48.8%) in the chemoradiotherapy group versus 33.0% (95% CI 23.6%-42.7%) in the chemotherapy group, P = 0.82. Five-year overall survival was 42.2% (95% CI 31.9%-52.1%) versus 39.6% (95% CI 29.5%-49.4%), P = 0.60. There were no differences in recurrence patterns between the treatment groups. This is to our knowledge that the largest completed randomized trial comparing neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy followed by esophageal resection in patients with cancer in the esophagus or gastroesophageal junction. Despite a higher tumor tissue response in those who received neoadjuvant chemoradiotherapy, no survival advantages were seen. Consequently, the results do not support unselected addition of radiotherapy to neoadjuvant chemotherapy as a standard of care in patients with resectable esophageal cancer.

Highly malignant routine EEG predicts poor prognosis after cardiac arrest in the Target Temperature Management trial.

INTRODUCTION: Routine EEG is widely used and accessible for post arrest neuroprognostication. Recent studies, using standardised EEG terminology, have proposed highly malignant EEG patterns with promising predictive ability. OBJECTIVES: To validate the performance of standardised routine EEG patterns to predict neurological outcome after cardiac arrest. METHODS: In the prospective multicenter Target Temperature Management trial, comatose cardiac arrest patients were randomised to different temperature levels (950 patients, 36 sites). According to the prospective protocol a routine EEG was performed in patients who remained comatose after the 36 h temperature control intervention. EEGs were retrospectively reviewed blinded to outcome using the standardised American Clinical Neurophysiology Society terminology. Highly malignant, malignant and benign EEG patterns were correlated to poor and good outcome, defined by best achieved Cerebral Performance Category up to 180 days. RESULTS: At 20 sites 207 patients had a routine EEG performed at median 76 h after cardiac arrest. Highly malignant patterns (suppression or burst-suppression with or without discharges) had a high specificity for poor outcome (98%, CI 92-100), but with limited sensitivity (31%, CI 24-39). Our false positive patient had a burst-suppression pattern during ongoing sedation. A benign EEG, i.e. continuous normal-voltage background without malignant features, identified patients with good outcome with 77% (CI 66-86) sensitivity and 80% (CI 73-86) specificity. CONCLUSION: Highly malignant routine EEG after targeted temperature management is a strong predictor of poor outcome. A benign EEG is an important indicator of a good outcome for patients remaining in coma.

Time to epileptiform activity and EEG background recovery are independent predictors after cardiac arrest.

OBJECTIVE: Investigate the temporal development of EEG and prognosis. METHODS: Prospective observational substudy of the Target Temperature Management trial. Six sites performed simplified continuous EEG-monitoring (cEEG) on comatose patients after cardiac arrest, blinded to treating physicians. We determined time-points of recovery of a normal-voltage continuous background activity and the appearance of an epileptiform EEG, defined as abundant epileptiform discharges, periodic/rhythmic discharges or electrographic seizure activity. RESULTS: 134 patients were included, 65 had a good outcome. Early recovery of continuous background activity (within 24 h) occurred in 72 patients and predicted good outcome since 55 (76%) had good outcome, increasing the odds for a good outcome seven times compared to a late background recovery. Early appearance of an epileptiform EEG occurred in 38 patients and 34 (89%) had a poor outcome, increasing the odds for a poor outcome six times compared to a late debut. The time to background recovery and the time to epileptiform activity were highly associated with outcome and levels of neuron-specific enolase. Multiple regression analysis showed that both variables were independent predictors. CONCLUSIONS: Time to epileptiform activity and background recovery are independent prognostic indicators. SIGNIFICANCE: Patients with early background recovery combined with late appearance of epileptiform activity may have a good outcome.

Lactate, lactate clearance and outcome after cardiac arrest: A post-hoc analysis of the TTM-Trial.

BACKGROUND: Admission lactate and lactate clearance are implemented for risk stratification in sepsis and trauma. In out-of-hospital cardiac arrest, results regarding outcome and lactate are conflicting. METHODS: This is a post-hoc analysis of the Target Temperature Management trial in which 950 unconscious patents after out-of-hospital cardiac arrest were randomized to a temperature intervention of 33°C or 36°C. Serial lactate samples during the first 36 hours were collected. Admission lactate, 12-hour lactate, and the clearance of lactate within 12 hours after admission were analyzed and the association with 30-day mortality assessed. RESULTS: Samples from 877 patients were analyzed. In univariate logistic regression analysis, the odds ratio for death by day 30 for each mmol/L was 1.12 (1.08-1.16) for admission lactate, P < .01, 1.21 (1.12-1.31) for 12-hour lactate, P < .01, and 1.003 (1.00-1.01) for each percentage point increase in 12-hour lactate clearance, P = .03. Only admission lactate and 12-hour lactate levels remained significant after adjusting for known predictors of outcome. The area under the receiver operating characteristic curve was 0.65 (0.61-0.69), P < .001, 0.61 (0.57-0.65), P < .001, and 0.53 (0.49-0.57), P = .15 for admission lactate, 12-hour lactate, and 12-hour lactate clearance, respectively. CONCLUSIONS: Admission lactate and 12-hour lactate values were independently associated with 30-day mortality after out-of-hospital cardiac arrest while 12-hour lactate clearance was not. The clinical value of lactate as the sole predictor of outcome after out-of-hospital cardiac arrest is, however, limited.

The analgesic effect of a popliteal plexus blockade after total knee arthroplasty: A feasibility study.

INTRODUCTION: An obturator nerve block (ONB) and a femoral triangle block (FTB) provide effective analgesia after total knee arthroplasty (TKA) without impeding the ambulation, although the ONB produces motor blockade of the hip adductor muscles. The popliteal plexus (PP) in the popliteal fossa is formed by contribution from the tibial nerve and the posterior obturator nerve, innervating intraarticular genicular structures and the posterior capsule of the knee. We hypothesised that a popliteal plexus block (PPB) as a supplement to an FTB would reduce pain after TKA without anaesthetising motor branches from the sciatic nerve in the popliteal fossa. AIM: To assess the analgesic effect of adding a PPB to an FTB in 10 subjects with significant pain after TKA. METHODS: All subjects underwent unilateral TKA with spinal anaesthesia and received an FTB. The cutaneous sensation and the postoperative pain were assessed. The primary outcome was the proportion of subjects with pain above numeric rating scale (NRS) 3 followed by a reduction to NRS 3 or below after conducting a PPB. RESULTS: Ten subjects with a median pain of NRS 5.5 (interquartile range [IQR] 4-8) after unilateral TKA received a PPB. All 10 subjects experienced a reduction in pain to NRS 3 or below (NRS 1.5 [IQR 0-3]) within a mean time of 8.5 (95% CI 6.8-10.2) minutes. Three subjects were completely pain free after the PPB. The ankle muscle strength was not affected. CONCLUSIONS: The PPB provided effective pain relief without affecting the ankle muscle strength in all 10 subjects with significant pain after TKA and an FTB.

Spread of injectate around hip articular sensory branches of the femoral nerve in cadavers.

BACKGROUND: Anatomical knowledge dictates that regional anaesthesia after total hip arthroplasty requires blockade of the hip articular branches of the femoral and obturator nerves. A direct femoral nerve block increases the risk of fall and impedes mobilisation. We propose a selective nerve block of the hip articular branches of the femoral nerve by an ultrasound-guided injection in the plane between the iliopsoas muscle and the iliofemoral ligament (the iliopsoas plane). The aim of this study was to assess whether dye injected in the iliopsoas plane spreads to all hip articular branches of the femoral nerve. METHODS: Fifteen cadaver sides were injected with 5 mL dye in the iliopsoas plane guided by ultrasound. Dissection was performed to verify the spread of injectate around the hip articular branches of the femoral nerve. RESULTS: In 10 dissections (67% [95% confidence interval: 38-88%]), the injectate was contained in the iliopsoas plane staining all hip articular branches of the femoral nerve without spread to motor branches. In four dissections (27% [8-55%]), the injection was unintentionally made within the iliopectineal bursa resulting in secondary spread. In one dissection (7% [0.2-32%]) adhesions partially obstructed the spread of dye. CONCLUSION: An injection of 5 mL in the iliopsoas plane spreads around all hip articular branches of the femoral nerve in 10 of 15 cadaver sides. If these findings translate to living humans, injection of local anaesthetic into the iliopsoas plane could generate a selective sensory nerve block of the articular branches of the femoral nerve without motor blockade.