In this multicenter randomized, controlled trial, withholding parenteral nutrition from critically ill children in the pediatric intensive care unit for 1 week was clinically superior to providing ...early parenteral nutrition. Fluid loading was provided in both groups.
Critically ill children cannot normally be fed by mouth, and as a result a pronounced macronutrient deficit often develops after a few days. This macronutrient deficit has been associated with infections, weakness, prolonged mechanical ventilation, and delayed recovery.
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In order to prevent or limit the development of this macronutrient deficit, current guidelines, which are based largely on small studies with surrogate end points and on expert opinion, advise care providers to initiate nutritional support soon after a child’s admission to the pediatric intensive care unit (ICU).
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The preferred route for the administration of nutritional support in the pediatric . . .
This controlled, randomized, multicenter trial compared early initiation (<2 days) with late initiation (≥8 days) of parenteral nutrition in adults in the intensive care unit. Late initiation was ...associated with less morbidity and enhanced recovery.
Critical illness induces anorexia and the inability to eat normally, predisposing patients to serious nutritional deficits, muscle wasting, weakness, and delayed recovery. Whether artificial nutritional support improves the outcome for critically ill patients is unclear. The administration route, the time until the initiation of artificial nutrition, the number of calories, and the type of nutrients may be important.
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Enteral nutrition is associated with fewer complications than parenteral nutrition and is less expensive to administer.
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However, the use of enteral nutrition alone often does not achieve caloric targets.
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In addition, underfeeding is associated with weakness, infection,
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an increased duration . . .
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.
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.
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.
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).
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).
Patients who are critically ill can develop so-called intensive-care unit acquired weakness, which delays rehabilitation. Reduced muscle mass, quality, or both might have a role. The Early Parenteral ...Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) trial (registered with ClinicalTrials.gov, number NCT00512122) showed that tolerating macronutrient deficit for 1 week in intensive-care units (late parenteral nutrition PN) accelerated recovery compared with early PN. The role of weakness was unclear. Our aim was to assess whether late PN and early PN differentially affect muscle weakness and autophagic quality control of myofibres.
In this prospectively planned subanalysis of the EPaNIC trial, weakness (MRC sum score) was assessed in 600 awake, cooperative patients. Skeletal muscle biopsies, harvested from 122 patients 8 days after randomisation and from 20 matched healthy controls, were studied for autophagy and atrophy. We determined the significance of differences with Mann-Whitney U, Median, Kruskal-Wallis, or χ(2) (exact) tests, as appropriate.
With late PN, 105 (34%) of 305 patients had weakness on first assessment (median day 9 post-randomisation) compared with 127 (43%) of 295 patients given early PN (absolute difference -9%, 95% CI -16 to -1; p=0·030). Weakness recovered faster with late PN than with early PN (p=0·021). Myofibre cross-sectional area was less and density was lower in critically ill patients than in healthy controls, similarly with early PN and late PN. The LC3 (microtubule-associated protein light chain 3) II to LC3I ratio, related to autophagosome formation, was higher in patients given late PN than early PN (p=0·026), reaching values almost double those in the healthy control group (p=0·0016), and coinciding with less ubiquitin staining (p=0·019). A higher LC3II to LC3I ratio was independently associated with less weakness (p=0·047). Expression of mRNA encoding contractile myofibrillary proteins was lower and E3-ligase expression higher in muscle biopsies from patients than in control participants (p≤0·0006), but was unaffected by nutrition.
Tolerating a substantial macronutrient deficit early during critical illness did not affect muscle wasting, but allowed more efficient activation of autophagic quality control of myofibres and reduced weakness.
UZ Leuven, Research Foundation-Flanders, the Flemish Government, and the European Research Council.
Context: Hyper- and hypoglycemia are associated with increased mortality of critically ill patients, but whether this association is causal remains unclear. Early randomized-controlled studies ...compared insulin infusion targeting “age-normal” blood glucose levels, labeled intensive insulin therapy, with an approach that considered hyperglycemia as a beneficial adaptation. These studies found benefits with maintaining normoglycemia. A recent large multicenter study, NICE-SUGAR, compared a similar age-normal with an intermediate glucose target and found the intermediate target superior. These results require explanation.
Evidence Acquisition: All published randomized controlled studies on glucose control in ICU were reviewed. The methodological differences between the repeat studies, most specifically NICE-SUGAR, and the original proof-of-concept studies, were systematically analyzed.
Evidence Synthesis: There were important methodological differences, possibly explaining different outcomes. These comprised different target ranges for blood glucose in control and intervention groups, different routes for insulin administration and types of infusion-pumps, different sampling sites, and different accuracies of glucometers, as well as different nutritional strategies and varying levels of expertise.
Conclusions: These differences do not permit confident recommendations for a single optimal glucose target in variable ICU settings. Respecting the “primum non nocere” principle, it appears safe not to embark on targeting age-normal levels in ICUs that are not equipped to accurately and frequently measure blood glucose and have not acquired extensive experience with iv insulin administration using a customized guideline. A simple overall fall-back position could be to maintain blood glucose levels as close to normal as possible without evoking unacceptable fluctuations, hypoglycemia, and hypokalemia.
The goal of intensive insulin therapy for critically ill patients is to control blood glucose levels asclose to normal as possible, without evoking unacceptable glucose fluctuations, hypoglycemia, or hypokalemia.
We examined whether liposome bupivacaine (Exparel) given in the interscalene brachial plexus block lowers pain in the setting of multimodal postoperative pain management for major shoulder surgery.
...Fifty-two adult patients were randomized to receive either 5 mL of 0.25% bupivacaine HCl immediately followed by 10 mL of liposome bupivacaine 133 mg (n = 26) or 15 mL of 0.25% standard bupivacaine alone (n = 26) in interscalene brachial plexus block. The primary outcome (worst pain in the first postoperative week) was assessed by the Modified Brief Pain Inventory short form. Secondary outcomes were overall satisfaction with analgesia (OBAS), functionality of the surgical arm, sleep duration, time to first opioid (tramadol) request and opioid consumption (mEq), sensory-motor block characteristics, and the occurrence of adverse effects.
Worst pain was lower in patients given liposome bupivacaine added to standard bupivacaine than in patients given standard bupivacaine alone (generalized estimating equation GEE estimated marginal mean values, 3.6 ± 0.3 vs 5.3 ± 0.4 points on the Numeric Rating Scale, respectively, although the effect was modest, 1.6 ± 0.5; 95% confidence interval, 0.8-2.5). Total OBAS scores indicated greater satisfaction (GEE estimated marginal mean values, 1.8 ± 0.3 vs 3.3 ± 0.4 on total OBAS, respectively, with modest effect, difference, 1.4 ± 0.5; 95% confidence interval, 0.5-2.4). There were no differences in any of the other secondary outcomes.
Liposome bupivacaine added to standard bupivacaine may lower pain and enhance patient's satisfaction in the first postoperative week even in the setting of multimodal analgesia for major shoulder surgery.This study was registered with clinicaltrials.gov (NCT02554357) on July 11, 2015, by Principal Investigator Catherine Vandepitte, MD.
Summary Background Critically ill infants and children often develop hyperglycaemia, which is associated with adverse outcome; however, whether lowering blood glucose concentrations to age-adjusted ...normal fasting values improves outcome is unknown. We investigated the effect of targeting age-adjusted normoglycaemia with insulin infusion in critically ill infants and children on outcome. Methods In a prospective, randomised controlled study, we enrolled 700 critically ill patients, 317 infants (aged <1 year) and 383 children (aged ≥1 year), who were admitted to the paediatric intensive care unit (PICU) of the University Hospital of Leuven, Belgium. Patients were randomly assigned by blinded envelopes to target blood glucose concentrations of 2·8–4·4 mmol/L in infants and 3·9–5·6 mmol/L in children with insulin infusion throughout PICU stay (intensive group n=349), or to insulin infusion only to prevent blood glucose from exceeding 11·9 mmol/L (conventional group n=351). Patients and laboratory staff were blinded to treatment allocation. Primary endpoints were duration of PICU stay and inflammation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00214916. Findings Mean blood glucose concentrations were lower in the intensive group than in the conventional group (infants: 4·8 SD 1·2 mmol/L vs 6·4 1·2 mmol/L, p<0·0001; children: 5·3 1·1 mmol/L vs 8·2 3·3 mmol/L, p<0·0001). Hypoglycaemia (defined as blood glucose ≤2·2 mmol/L) occurred in 87 (25%) patients in the intensive group (p<0·0001) versus five (1%) patients in the conventional group; hypoglycaemia defined as blood glucose less than 1·7 mmol/L arose in 17 (5%) patients versus three (1%) (p=0·001). Duration of PICU stay was shortest in the intensively treated group (5·51 days 95% CI 4·65–6·37 vs 6·15 days 5·25–7·05, p=0·017). The inflammatory response was attenuated at day 5, as indicated by lower C-reactive protein in the intensive group compared with baseline (−9·75 mg/L 95% CI −19·93 to 0·43 vs 8·97 mg/L −0·9 to 18·84, p=0·007). The number of patients with extended (>median) stay in PICU was 132 (38%) in the intensive group versus 165 (47%) in the conventional group (p=0·013). Nine (3%) patients died in the intensively treated group versus 20 (6%) in the conventional group (p=0·038). Interpretation Targeting of blood glucose concentrations to age-adjusted normal fasting concentrations improved short-term outcome of patients in PICU. The effect on long-term survival, morbidity, and neurocognitive development needs to be investigated. Funding Research Foundation (Belgium); Research Fund of the University of Leuven (Belgium) and the EU Information Society Technologies Integrated project “CLINICIP”; and Institute for Science and Technology (Belgium).
OBJECTIVE:The goal of enhanced nutrition in critically ill patients is to improve outcome by reducing lean tissue wasting. However, such effect has not been proven. This study aimed to assess the ...effect of early administration of parenteral nutrition on muscle volume and composition by repeated quantitative CT.
DESIGN:A preplanned substudy of a randomized controlled trial (Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients EPaNIC), which compared early initiation of parenteral nutrition when enteral nutrition was insufficient (early parenteral nutrition) with tolerating a pronounced nutritional deficit for 1 week in ICU (late parenteral nutrition). Late parenteral nutrition prevented infections and accelerated recovery.
SETTING:University hospital.
PATIENTS:Fifteen EPaNIC study neurosurgical patients requiring prescheduled repeated follow-up CT scans and six healthy volunteers matched for age, gender, and body mass index.
INTERVENTION:Repeated abdominal and femoral quantitative CT images were obtained in a standardized manner on median ICU day 2 (interquartile range, 2–3) and day 9 (interquartile range, 8–10). Intramuscular, subcutaneous, and visceral fat compartments were delineated manually. Muscle and adipose tissue volume and composition were quantified using standard Hounsfield Unit ranges.
MEASUREMENTS AND MAIN RESULTS:Critical illness evoked substantial loss of femoral muscle volume in 1 week’s time, irrespective of the nutritional regimen. Early parenteral nutrition reduced the quality of the muscle tissue, as reflected by the attenuation, revealing increased intramuscular water/lipid content. Early parenteral nutrition also increased the volume of adipose tissue islets within the femoral muscle compartment. These changes in skeletal muscle quality correlated with caloric intake. In the abdominal muscle compartments, changes were similar, albeit smaller. Femoral and abdominal subcutaneous adipose tissue compartments were unaffected by disease and nutritional strategy.
CONCLUSIONS:Early parenteral nutrition did not prevent the pronounced wasting of skeletal muscle observed over the first week of critical illness. Furthermore, early parenteral nutrition increased the amount of adipose tissue within the muscle compartments.
Intranasal administration of dexmedetomidine for monitored anesthesia care (MAC) appears to be an effective, safe, and appropriate alternative to general anesthesia (GA) for ambulatory dental ...surgery. Based on the available evidence we evaluated a new MAC protocol with intranasal dexmedetomidine as the primary choice. To assess a difference in patient satisfaction and anesthesia-related discomfort between GA and MAC in ambulatory dental surgery, a study was conducted among patients undergoing various dental procedures. Patient satisfaction and anesthesia-related discomfort were assessed on the first postoperative day using the Bauer patient satisfaction questionnaire.
Although the differences were small, patients in the MAC group were overall more satisfied with the general care compared to the GA group (p < 0.02). Patients in the MAC group reported more postoperative drowsiness compared to the GA group (p < 0.05), but less postoperative hoarseness and sore throat (p = 0.005 and p < 0.001, respectively). Moreover, postoperative thirst was more common in the GA group (p = 0.002). In conclusion, the differences in patient satisfaction and anesthesia-related discomfort between GA and MAC in this implementation study were small but appeared to favor MAC with intranasal dexmedetomidine over GA as anesthesia method during dental ambulatory surgery.
Abstract
The immune response in patients with Coronavirus Disease 2019 (COVID-19) is highly variable and is linked to disease severity and mortality. However, antibody and cytokine responses in the ...early disease stage and their association with disease course and outcome are still not completely understood. In this large, multi-centre cohort study, blood samples of 434 Belgian COVID-19 hospitalized patients with different disease severities (ranging from asymptomatic/mild to critically ill) from the first wave of the COVID-19 pandemic were obtained. Baseline antibody and cytokine responses were characterized and associations with several clinical outcome parameters were determined. Anti-spike immunoglobulin (Ig)G and IgM levels were elevated in patients with a more severe disease course. This increased baseline antibody response however was associated with decreased odds for hospital mortality. Levels of the pro-inflammatory cytokines IL-6, IP-10 and IL-8, the anti-inflammatory cytokine IL-10 and the antiviral cytokines IFN-α, IFN-β and IFN-λ1 were increased with disease severity. Remarkably, we found significantly lower levels of IFN-λ2,3 in critically ill patients compared to patients of the moderate and severe disease category. Finally, levels of IL-8, IL-6, IP-10, IL-10, IFN-α, IFN-β, IFN-γ and IFN-λ1 at baseline were positively associated with mortality, whereas higher IFN-λ2,3 levels were negatively associated with mortality.
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