Long-Term Outcome in Patients With Spinal Cord Stimulation for Failed Back Surgery Syndrome: A 20-Year Audit of a Single Center.

STUDY DESIGN: This is a retrospective, observational study. INTRODUCTION: Spinal cord stimulation (SCS) has found its application in chronic pain treatment, with failed back surgery syndrome (FBSS) as one of the most important indications. However, to date, little is known about the long-term effectiveness of the treatment. The aim of this study is to analyze retrospectively the long-term outcomes of SCS treatment in a single multidisciplinary pain center on predominant radicular pain, using devices of a single manufacturer. MATERIALS AND METHODS: Patient data on overall patient satisfaction, pain intensity, and adverse events were retrospectively collected in our clinical practice between January 1998 and January 2018, for 191 patients who received a permanent SCS implant. Secondary health measures included the influence of opioid and nicotine use on pain reduction after therapy. RESULTS: The trial-to-implant ratio was 93.6%. At a mean follow-up of 10.6 years, 78.5% of the patients were satisfied with the treatment outcome, with a significant pain reduction of an average three points on a Numeric Rating Scale. Opioid and nicotine usage did not have a significant link with the pain reduction one year after the treatment. Furthermore, devices had an average battery lifespan of 8.4 years. A total of 248 revisions were recorded. A total of 24 patients (11.7%) acquired an infection; 7 of 204 patients had an infection during the trial period, 2 of 191 patients had an infection in the first postoperative year, and 15 of 191 patients had an infection after the first year. The average time to infection, if not in the first year, was 10.1 years. CONCLUSIONS: A successful long-term outcome regarding pain relief in patients with predominant radicular pain due to FBSS is established with SCS therapy.

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.

Acute kidney injury in critical COVID-19: a multicenter cohort analysis in seven large hospitals in Belgium.

BACKGROUND: Acute kidney injury (AKI) has been reported as a frequent complication of critical COVID-19. We aimed to evaluate the occurrence of AKI and use of kidney replacement therapy (KRT) in critical COVID-19, to assess patient and kidney outcomes and risk factors for AKI and differences in outcome when the diagnosis of AKI is based on urine output (UO) or on serum creatinine (sCr). METHODS: Multicenter, retrospective cohort analysis of patients with critical COVID-19 in seven large hospitals in Belgium. AKI was defined according to KDIGO within 21 days after ICU admission. Multivariable logistic regression analysis was used to explore the risk factors for developing AKI and to assess the association between AKI and ICU mortality. RESULTS: Of 1286 patients, 85.1% had AKI, and KRT was used in 9.8%. Older age, obesity, a higher APACHE II score and use of mechanical ventilation at day 1 of ICU stay were associated with an increased risk for AKI. After multivariable adjustment, all AKI stages were associated with ICU mortality. AKI was based on sCr in 40.1% and UO in 81.5% of patients. All AKI stages based on sCr and AKI stage 3 based on UO were associated with ICU mortality. Persistent AKI was present in 88.6% and acute kidney disease (AKD) in 87.6%. Rapid reversal of AKI yielded a better prognosis compared to persistent AKI and AKD. Kidney recovery was observed in 47.4% of surviving AKI patients. CONCLUSIONS: Over 80% of critically ill COVID-19 patients had AKI. This was driven by the high occurrence rate of AKI defined by UO criteria. All AKI stages were associated with mortality (NCT04997915).

Effect of Lidocaine 2% Versus Bupivacaine 0.5% and 1 Versus 2 Dual Separate Injections on Onset and Duration of Ultrasound-Guided Wrist Blocks: A Blinded 2 × 2 Factorial Randomized Clinical Trial.

BACKGROUND: Local anesthetics are often selected or mixed to accomplish faster onset of anesthesia. However, with ultrasound guidance, local anesthetics are delivered with greater precision, which may shorten the onset time with all classes of local anesthetics. In this study, we compared onset time and duration of ultrasound-guided wrist blocks with a fast onset versus a longer lasting local anesthetic administered via single or dual (spatially separate) injections at the level of the midforearm. METHODS: In this randomized clinical trial, 36 subjects scheduled for carpal tunnel release were randomly assigned to receive ultrasound-guided median and ulnar nerve blocks with lidocaine 2% or bupivacaine 0.5% via single or dual injections (n = 9 in each group). Subjects fulfilled the study requirements. The main outcome variables were onset and duration of sensory blockade, which were tested separately in 2 (drug) × 2 (injection) analysis of variances (ANOVAs) with interaction terms. RESULTS: Sensory block onset time did not differ significantly between subjects given lidocaine 2% (9.2 ± 3.4 minutes) or bupivacaine 0.5% (9.5 ± 3.1 minutes) (P = .76; mean difference, -0.3 ± 1.1 minutes [95% confidence interval {CI}, -2.5 to 1.9]) or between the single- (9.6 ± 2.8 minutes) and dual- (9.1 ± 3.6 minutes) injection groups (P = .69; mean difference, -0.4 ± 1.1 minutes [95% CI, -1.8 to 2.6]). Sensory duration was longer for subjects in the bupivacaine 0.5% group (27.3 ± 11.6 hours) than for subjects in the lidocaine 2% group (8.4 ± 4.1 hours) (P < .001; 95% CI, 12.7-25.1). However, sensory duration in the single- (15.7 ± 12.5 hours) and dual- (19.4 ± 13.1 hours) injection groups did not differ significantly (P = .28; mean difference, -3.7 ± 4.3 hours [95% CI, -12.6 to 5.1]). CONCLUSIONS: No significant effect was found for onset time between lidocaine 2% and bupivacaine 0.5% used in ultrasound-guided wrist blocks. Dual injections did not shorten onset time. Since mean nerve block duration was longer with bupivacaine 0.5%, our results suggest that the selection of local anesthetic for the median and ulnar nerves at the level of the midforearm should be based on the desired duration of the block and not on its speed of onset.

A retrospective study on patients with chronic knee pain treated with ultrasound-guided radiofrequency of the genicular nerves (RECORGEN trial).

INTRODUCTION: Radiofrequency (RF) treatment of the genicular nerves is a promising treatment for chronic osteoarthritic and persistent postsurgical knee pain (PPSP), refractory to conventional medical management. METHODS: The RECORGEN study is a retrospective single-center cohort study of patients treated with ultrasound-guided conventional RF of the genicular nerves for chronic knee pain in Hospital Oost-Limburg, Genk from September 2017 to June 2020. Subgroup analysis based on etiology of pain (PPSP and degenerative knee pain) was performed in addition to the total study population analysis. Outcome parameters were global perceived effect (GPE), Numeric Rating Scale for pain, consumption of strong opioids, and safety of the treatment at 6 weeks and cross-sectionally at a variable time point. Treatment success was defined as GPE≥50%. RESULTS: Sixty-eight cases were screened of which 59 (46 diagnosed with PPSP and 13 with degenerative knee pain) were included in the study. Treatment success at 6 weeks was achieved in 19 of 59 interventions (32.2%) and was similar in both groups. Seventeen responders were evaluated at follow-up. 45.1% (8/17) continued to have a positive effect at the second time point. The mean duration of effect of the RF treatment was 8.3 months. Safety analysis at 6 weeks and at the second time point showed a good safety profile of the treatment. CONCLUSION: Conventional RF of the genicular nerves was clinically successful in more than 30% of the study population refractory to conventional medical management. Overall, the treatment was well tolerated. The mean duration of effect was 8.3 months.

Vital Signs Prediction for COVID-19 Patients in ICU.

This study introduces machine learning predictive models to predict the future values of the monitored vital signs of COVID-19 ICU patients. The main vital sign predictors include heart rate, respiration rate, and oxygen saturation. We investigated the performances of the developed predictive models by considering different approaches. The first predictive model was developed by considering the following vital signs: heart rate, blood pressure (systolic, diastolic and mean arterial, pulse pressure), respiration rate, and oxygen saturation. Similar to the first approach, the second model was developed using the same vital signs, but it was trained and tested based on a leave-one-subject-out approach. The third predictive model was developed by considering three vital signs: heart rate (HR), respiration rate (RR), and oxygen saturation (SpO2). The fourth model was a leave-one-subject-out model for the three vital signs. Finally, the fifth predictive model was developed based on the same three vital signs, but with a five-minute observation rate, in contrast with the aforementioned four models, where the observation rate was hourly to bi-hourly. For the five models, the predicted measurements were those of the three upcoming observations (on average, three hours ahead). Based on the obtained results, we observed that by limiting the number of vital sign predictors (i.e., three vital signs), the prediction performance was still acceptable, with the average mean absolute percentage error (MAPE) being 12%,5%, and 21.4% for heart rate, oxygen saturation, and respiration rate, respectively. Moreover, increasing the observation rate could enhance the prediction performance to be, on average, 8%,4.8%, and 17.8% for heart rate, oxygen saturation, and respiration rate, respectively. It is envisioned that such models could be integrated with monitoring systems that could, using a limited number of vital signs, predict the health conditions of COVID-19 ICU patients in real-time.

Association between postoperative delirium and postoperative cerebral oxygen desaturation in older patients after cardiac surgery.

BACKGROUND: Near-infrared spectroscopy non-invasively measures regional cerebral oxygen saturation. Intraoperative cerebral desaturations have been associated with worse neurological outcomes. We investigated whether perioperative cerebral desaturations are associated with postoperative delirium in older patients after cardiac surgery. METHODS: Patients aged 70 yr and older scheduled for on-pump cardiac surgery were included between 2015 and 2017 in a single-centre, prospective, observational study. Baseline cerebral oxygen saturation was measured 1 day before surgery. Throughout surgery and after ICU admission, cerebral oxygen saturation was monitored continuously up to 72 h after operation. The presence of delirium was assessed using the confusion assessment method for the ICU. Association with delirium was evaluated with unadjusted analyses and multivariable logistic regression. RESULTS: Ninety-six of 103 patients were included, and 29 (30%) became delirious. Intraoperative cerebral oxygen saturation was not significantly associated with postoperative delirium. The lowest postoperative cerebral oxygen saturation was lower in patients who became delirious (P=0.001). The absolute and relative postoperative cerebral oxygen saturation decreases were more marked in patients with delirium (13 [6]% and 19 [9]%, respectively) compared with patients without delirium (9 [4]% and 14 [5]%; P=0.002 and P=0.001, respectively). These differences in cerebral oxygen saturation were no longer present after excluding cerebral oxygen saturation values after patients became delirious. Older age, previous stroke, higher EuroSCORE II, lower preoperative Mini-Mental Status Examination, and more substantial absolute postoperative cerebral oxygen saturation decreases were independently associated with postoperative delirium incidence. CONCLUSIONS: Postoperative delirium in older patients undergoing cardiac surgery is associated with absolute decreases in postoperative cerebral oxygen saturation. These differences appear most detectable after the onset of delirium. CLINICAL TRIAL REGISTRATION: NCT02532530.

Hepatic PPARα is critical in the metabolic adaptation to sepsis.

BACKGROUND & AIMS: Although the role of inflammation to combat infection is known, the contribution of metabolic changes in response to sepsis is poorly understood. Sepsis induces the release of lipid mediators, many of which activate nuclear receptors such as the peroxisome proliferator-activated receptor (PPAR)α, which controls both lipid metabolism and inflammation. We aimed to elucidate the previously unknown role of hepatic PPARα in the response to sepsis. METHODS: Sepsis was induced by intraperitoneal injection of Escherichia coli in different models of cell-specific Ppara-deficiency and their controls. The systemic and hepatic metabolic response was analyzed using biochemical, transcriptomic and functional assays. PPARα expression was analyzed in livers from elective surgery and critically ill patients and correlated with hepatic gene expression and blood parameters. RESULTS: Both whole body and non-hematopoietic Ppara-deficiency in mice decreased survival upon bacterial infection. Livers of septic Ppara-deficient mice displayed an impaired metabolic shift from glucose to lipid utilization resulting in more severe hypoglycemia, impaired induction of hyperketonemia and increased steatosis due to lower expression of genes involved in fatty acid catabolism and ketogenesis. Hepatocyte-specific deletion of PPARα impaired the metabolic response to sepsis and was sufficient to decrease survival upon bacterial infection. Hepatic PPARA expression was lower in critically ill patients and correlated positively with expression of lipid metabolism genes, but not with systemic inflammatory markers. CONCLUSION: During sepsis, Ppara-deficiency in hepatocytes is deleterious as it impairs the adaptive metabolic shift from glucose to FA utilization. Metabolic control by PPARα in hepatocytes plays a key role in the host defense against infection. LAY SUMMARY: As the main cause of death in critically ill patients, sepsis remains a major health issue lacking efficacious therapies. While current clinical literature suggests an important role for inflammation, metabolic aspects of sepsis have mostly been overlooked. Here, we show that mice with an impaired metabolic response, due to deficiency of the nuclear receptor PPARα in the liver, exhibit enhanced mortality upon bacterial infection despite a similar inflammatory response, suggesting that metabolic interventions may be a viable strategy for improving sepsis outcomes.

Early versus Late Parenteral Nutrition in Critically Ill Children.

BACKGROUND: Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear. METHODS: We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided. RESULTS: Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients receiving renal-replacement therapy (P=0.04) and a shorter duration of hospital stay (P=0.001). Late parenteral nutrition was also associated with lower plasma levels of γ-glutamyltransferase and alkaline phosphatase than was early parenteral nutrition (P=0.001 and P=0.04, respectively), as well as higher levels of bilirubin (P=0.004) and C-reactive protein (P=0.006). CONCLUSIONS: In critically ill children, withholding parenteral nutrition for 1 week in the ICU was clinically superior to providing early parenteral nutrition. (Funded by the Flemish Agency for Innovation through Science and Technology and others; ClinicalTrials.gov number, NCT01536275.).

The Prognostic Value of Simplified EEG in Out-of-Hospital Cardiac Arrest Patients.

BACKGROUND: We previously validated simplified electroencephalogram (EEG) tracings obtained by a bispectral index (BIS) device against standard EEG. This retrospective study now investigated whether BIS EEG tracings can predict neurological outcome after cardiac arrest (CA). METHODS: Bilateral BIS monitoring (BIS VISTA™, Aspect Medical Systems, Inc. Norwood, USA) was started following intensive care unit admission. Six, 12, 18, 24, 36 and 48 h after targeted temperature management (TTM) at 33 °C was started, BIS EEG tracings were extracted and reviewed by two neurophysiologists for the presence of slow diffuse rhythm, burst suppression, cerebral inactivity and epileptic activity (defined as continuous, monomorphic, > 2 Hz generalized sharp activity or continuous, monomorphic, < 2 Hz generalized blunt activity). At 180 days post-CA, neurological outcome was determined using cerebral performance category (CPC) classification (CPC1-2: good and CPC3-5: poor neurological outcome). RESULTS: Sixty-three out-of-hospital cardiac arrest patients were enrolled for data analysis of whom 32 had a good and 31 a poor neurological outcome. Epileptic activity within 6-12 h predicted CPC3-5 with a positive predictive value (PPV) of 100%. Epileptic activity within time frames 18-24 and 36-48 h showed a PPV for CPC3-5 of 90 and 93%, respectively. Cerebral inactivity within 6-12 h predicted CPC3-5 with a PPV of 57%. In contrast, cerebral inactivity between 36 and 48 h predicted CPC3-5 with a PPV of 100%. The pattern with the worst predictive power at any time point was burst suppression with PPV of 44, 57 and 40% at 6-12 h, at 18-24 h and at 36-48 h, respectively. Slow diffuse rhythms at 6-12 h, at 18-24 h and at 36-48 h predicted CPC1-2 with PPV of 74, 76 and 80%, respectively. CONCLUSION: Based on simplified BIS EEG, the presence of epileptic activity at any time and cerebral inactivity after the end of TTM may assist poor outcome prognostication in successfully resuscitated CA patients. A slow diffuse rhythm at any time after CA was indicative for a good neurological outcome.

Plasma N-glycome composition associates with chronic low back pain.

BACKGROUND: Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease. METHODS: Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery. RESULTS: We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients' plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP. CONCLUSIONS: Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation. GENERAL SIGNIFICANCE: To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology.

Cost-effectiveness study of early versus late parenteral nutrition in critically ill children (PEPaNIC): preplanned secondary analysis of a multicentre randomised controlled trial.

BACKGROUND: The multicentre randomised controlled PEPaNIC trial showed that withholding parenteral nutrition (PN) during the first week of critical illness in children was clinically superior to providing early PN. This study describes the cost-effectiveness of this new nutritional strategy. METHODS: Direct medical costs were calculated with use of a micro-costing approach. We compared the costs of late versus early initiation of PN (n = 673 versus n = 670 patients) in the Belgian and Dutch study populations from a hospital perspective, using Student's t test with bootstrapping. Main cost drivers were identified and the impact of new infections on the total costs was assessed. RESULTS: Mean direct medical costs for patients receiving late PN (€26.680, IQR €10.090-28.830 per patient) were 21% lower (-€7.180, p = 0.007) than for patients receiving early PN (€33.860, IQR €11.080-34.720). Since late PN was more effective and less costly, this strategy was superior to early PN. The lower costs for PN only contributed 2.1% to the total cost reduction. The main cost driver was intensive care hospitalisation costs (-€4.120, p = 0.003). The patients who acquired a new infection (14%) were responsible for 41% of the total costs. Sensitivity analyses confirmed consistency across both healthcare systems. CONCLUSIONS: Late initiation of PN decreased the direct medical costs for hospitalisation in critically ill children, beyond the expected lower costs for withholding PN. Avoiding new infections by late initiation of PN yielded a large cost reduction. Hence, late initiation of PN was superior to early initiation of PN largely via its effect on new infections. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01536275 . Registered on 16 February 2012.

Software-guided versus nurse-directed blood glucose control in critically ill patients: the LOGIC-2 multicenter randomized controlled clinical trial.

BACKGROUND: Blood glucose control in the intensive care unit (ICU) has the potential to save lives. However, maintaining blood glucose concentrations within a chosen target range is difficult in clinical practice and holds risk of potentially harmful hypoglycemia. Clinically validated computer algorithms to guide insulin dosing by nurses have been advocated for better and safer blood glucose control. METHODS: We conducted an international, multicenter, randomized controlled trial involving 1550 adult, medical and surgical critically ill patients, requiring blood glucose control. Patients were randomly assigned to algorithm-guided blood glucose control (LOGIC-C, n = 777) or blood glucose control by trained nurses (Nurse-C, n = 773) during ICU stay, according to the local target range (80-110 mg/dL or 90-145 mg/dL). The primary outcome measure was the quality of blood glucose control, assessed by the glycemic penalty index (GPI), a measure that penalizes hypoglycemic and hyperglycemic deviations from the chosen target range. Incidence of severe hypoglycemia (<40 mg/dL) was the main safety outcome measure. New infections in ICU, duration of hospital stay, landmark 90-day mortality and quality of life were clinical safety outcome measures. RESULTS: The median GPI was lower in the LOGIC-C (10.8 IQR 6.2-16.1) than in the Nurse-C group (17.1 IQR 10.6-26.2) (P < 0.001). Mean blood glucose was 111 mg/dL (SD 15) in LOCIC-C versus 119 mg/dL (SD 21) in Nurse-C, whereas the median time-in-target range was 67.0% (IQR 52.1-80.1) in LOGIC-C versus 47.1% (IQR 28.1-65.0) in the Nurse-C group (both P < 0.001). The fraction of patients with severe hypoglycemia did not differ between LOGIC-C (0.9%) and Nurse-C (1.2%) (P = 0.6). The clinical safety outcomes did not differ between groups. The sampling interval was 2.3 h (SD 0.5) in the LOGIC-C group versus 3.0 h (SD 0.8) in the Nurse-C group (P < 0.001). CONCLUSIONS: In a randomized controlled trial of a mixed critically ill patient population, the use of the LOGIC-Insulin blood glucose control algorithm, compared with blood glucose control by expert nurses, improved the quality of blood glucose control without increasing hypoglycemia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02056353 . Registered on 4 February 2014.

Performance of strip-based glucose meters and cassette-based blood gas analyzer for monitoring glucose levels in a surgical intensive care setting.

BACKGROUND: We verified the analytical performance of strip-based handheld glucose meters (GM) for prescription use, in a comparative split-sample protocol using blood gas samples from a surgical intensive care unit (ICU). METHODS: Freestyle Precision Pro (Abbott), StatStrip Connectivity Meter (Nova), ACCU-CHEK Inform II (Roche) were evaluated for recovery/linearity, imprecision/repeatability. The GMs and the ABL90 (Radiometer) blood gas analyzer (BGA) were tested for relative accuracy vs. the comparator hexokinase glucose-6-phosphate-dehydrogenase (HK/G6PDH) assay on a Cobas c702 analyzer (Roche). RESULTS: Recovery of spiked glucose was linear up to 19.3 mmol/L (347 mg/dL) with a slope of 0.91-0.94 for all GMs. Repeatability estimated by pooling duplicate measurements on samples below (n=9), in (n=51) or above (n=80) the 4.2-5.9 mM (74-106 mg/dL) range were for Freestyle Precision Pro: 4.2%, 4.0%, 3.6%; StatStrip Connectivity Meter: 4.0%, 4.3%, 4.5%; and ACCU-CHEK Inform II: 1.4%, 2.5%, 3.5%. GMs were in agreement with the comparator method. The BGA outperformed the GMs, with a MARD of 3.9% compared to 6.5%, 5.8% and 4.4% for the FreeStyle, StatStrip and ACCU-CHEK, respectively. Zero % of the BGA results deviated more than the FDA 10% criterion as compared to 9.4%, 3.7% and 2.2% for the FreeStyle, StatStrip and ACCU-CHEK, respectively. For all GMs, icodextrin did not interfere. Variation in the putative influence factors hematocrit and O2 tension could not explain observed differences with the comparator method. CONCLUSIONS: GMs quantified blood glucose in whole blood at about the 10% total error criterion, proposed by the FDA for prescription use.

Sweet Spot: Glucose Control in the Intensive Care Unit.

Hyperglycemia, hypoglycemia, and glycemic variability are all independently associated with morbidity and mortality of critically ill patients. A strategy aiming at normoglycemia (so-called tight glycemic control) could improve outcomes of critically ill patients, but results from randomized controlled trials of tight glycemic control are conflicting. Strict glycemic control is associated with an increased risk of hypoglycemia, which could offset the benefit of this intervention. Notably, the risk of hypoglycemia is not necessarily removed with less tight glucose control regimens. The best targets of blood glucose control in critically ill patients, therefore, remain a matter of debate. It should be realized that blood glucose control is a complex intervention, consisting of many critical aspects that have the potential to affect its efficacy and safety. Efficacy, and in particular safety, of blood glucose control could still improve. First, glucose algorithms could overcome the lack of knowledge and skills of nursing staff when they are less experienced in safe and efficient blood glucose control. Several computerized glucose control algorithms have been developed over recent years, but they all need clinical validation. Also, the workload induced by such algorithms should be evaluated. Second, continuous blood glucose monitoring has the potential to improve safety and efficacy. Until recently, blood glucose levels were monitored manually using point-of-care devices with significant inaccuracies. Various continuous monitoring systems have been developed, but studies testing their accuracies and usefulness in an intensive care unit setting are highly needed.

Worldwide Survey of Nutritional Practices in PICUs.

OBJECTIVE: To assess current nutritional practices in critically ill children worldwide. DESIGN: A two-part online, international survey. The first part, "the survey", was composed of 59 questions regarding nutritional strategies and protocols (July-November 2013). The second part surveyed the "point prevalence" of nutritional data of patients present in a subgroup of the responding PICUs (May-September 2014). SETTING: Members of the World Federation of Pediatric Intensive and Critical Care Societies were asked to complete the survey. SUBJECTS: Pediatric critical care providers. INTERVENTIONS: Survey. MEASUREMENTS AND MAIN RESULTS: We analyzed 189 responses from 156 PICUs in 52 countries (survey). We received nutritional data on 295 patients from 41 of these 156 responding PICUs in 27 countries (point prevalence). According to the "survey", nutritional protocols and support teams were available in 52% and 57% of the PICUs, respectively. Various equations were in use to estimate energy requirements; only in 14% of PICUs, indirect calorimetry was used. Nutritional targets for macronutrients, corrected for age/weight, varied widely. Enteral nutrition would be started early (within 24 hr of admission) in 60% of PICUs, preferably by the gastric route (88%). In patients intolerant to enteral nutrition, parenteral nutrition would be started within 48 hours in 55% of PICUs. Overall, in 72% of PICUs supplemental parenteral nutrition would be used if enteral nutrition failed to meet at least 50% of energy delivery goal. Several differences between the intended (survey) and the actual (point prevalence) nutritional practices were found in the responding PICUs, predominantly overestimating the ability to adequately feed patients. CONCLUSION: Nutritional practices vary widely between PICUs worldwide. There are significant differences in macronutrient goals, estimating energy requirements, timing of nutrient delivery, and threshold for supplemental parenteral nutrition. Uniform consensus-based nutrition practices, preferably guided by evidence, are desirable in the PICU.

Withholding parenteral nutrition during critical illness increases plasma bilirubin but lowers the incidence of biliary sludge.

UNLABELLED: Cholestatic liver dysfunction (CLD) and biliary sludge often occur during critical illness and are allegedly aggravated by parenteral nutrition (PN). Delaying initiation of PN beyond day 7 in the intensive care unit (ICU) (late PN) accelerated recovery as compared with early initiation of PN (early PN). However, the impact of nutritional strategy on biliary sludge and CLD has not been fully characterized. This was a preplanned subanalysis of a large randomized controlled trial of early PN versus late PN (n = 4,640). In all patients plasma bilirubin (daily) and liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transpeptidase [GGT], alkaline phosphatase [ALP], twice weekly; n = 3,216) were quantified. In a random predefined subset of patients, plasma bile acids (BAs) were also quantified at baseline and on days 3, 5, and last ICU-day (n = 280). Biliary sludge was ultrasonographically evaluated on ICU-day 5 (n = 776). From day 1 after randomization until the end of the 7-day intervention window, bilirubin was higher in the late PN than in the early PN group (P < 0.001). In the late PN group, as soon as PN was started on day 8 bilirubin fell and the two groups became comparable. Maximum levels of GGT, ALP, and ALT were lower in the late PN group (P < 0.01). Glycine/taurine-conjugated primary BAs increased over time in ICU (P < 0.01), similarly for the two groups. Fewer patients in the late PN than in the early PN group developed biliary sludge on day 5 (37% versus 45%; P = 0.04). CONCLUSION: Tolerating substantial caloric deficit by withholding PN until day 8 of critical illness increased plasma bilirubin but reduced the occurrence of biliary sludge and lowered GGT, ALP, and ALT. These results suggest that hyperbilirubinemia during critical illness does not necessarily reflect cholestasis and instead may be an adaptive response that is suppressed by early PN.

Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis.

RATIONALE: Intensive care unit (ICU)-acquired weakness is a frequent complication of critical illness. It is unclear whether it is a marker or mediator of poor outcomes. OBJECTIVES: To determine acute outcomes, 1-year mortality, and costs of ICU-acquired weakness among long-stay (≥8 d) ICU patients and to assess the impact of recovery of weakness at ICU discharge. METHODS: Data were prospectively collected during a randomized controlled trial. Impact of weakness on outcomes and costs was analyzed with a one-to-one propensity-score-matching for baseline characteristics, illness severity, and risk factor exposure before assessment. Among weak patients, impact of persistent weakness at ICU discharge on risk of death after 1 year was examined with multivariable Cox proportional hazards analysis. MEASUREMENTS AND MAIN RESULTS: A total of 78.6% were admitted to the surgical ICU; 227 of 415 (55%) long-stay assessable ICU patients were weak; 122 weak patients were matched to 122 not-weak patients. As compared with matched not-weak patients, weak patients had a lower likelihood for live weaning from mechanical ventilation (hazard ratio [HR], 0.709 [0.549-0.888]; P = 0.009), live ICU (HR, 0.698 [0.553-0.861]; P = 0.008) and hospital discharge (HR, 0.680 [0.514-0.871]; P = 0.007). In-hospital costs per patient (+30.5%, +5,443 Euro per patient; P = 0.04) and 1-year mortality (30.6% vs. 17.2%; P = 0.015) were also higher. The 105 of 227 (46%) weak patients not matchable to not-weak patients had even worse prognosis and higher costs. The 1-year risk of death was further increased if weakness persisted and was more severe as compared with recovery of weakness at ICU discharge (P < 0.001). CONCLUSIONS: After careful matching the data suggest that ICU-acquired weakness worsens acute morbidity and increases healthcare-related costs and 1-year mortality. Persistence and severity of weakness at ICU discharge further increased 1-year mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00512122).