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Reassessing the Use of Proton Pump Inhibitors and Histamine-2 Antagonists in Critically Ill Children: A Systematic Review and Meta-Analysis.
Yao, DWJ, Ong, C, Eales, NM, Sultana, R, Wong, JJ, Lee, JH
The Journal of pediatrics. 2021;:164-176.e7
Abstract
OBJECTIVE To determine the associations of stress ulcer prophylaxis with gastrointestinal (GI) bleeding, nosocomial pneumonia (NP), mortality, and length of stay in the pediatric intensive care unit (PICU). STUDY DESIGN We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies in the English language assessing the effects of proton pump inhibitors and histamine-2 receptor antagonists on patients in the PICU published before October 2018 from the PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials databases. A random-effects Mantel-Haenszel risk difference (MHRD) model was used to pool all the selected studies for meta-analysis. Primary outcomes were the incidences of GI bleeding and NP. Secondary outcomes included mortality and length of PICU stay. RESULTS Seventeen studies (4 RCTs and 13 observational studies) with a total of 340 763 patients were included. The overall incidence of GI bleeding was 15.2%. There was no difference in the risk of GI bleeding based on stress ulcer prophylaxis status (MHRD, 5.0%; 95% CI, -1.0% to 11.0%; I2 = 62%). There was an increased risk of NP in patients who received stress ulcer prophylaxis compared with those who did not (MHRD, 5.3%; 95% CI, 3.5%-7.0%; I2 = 0%). An increased risk of mortality was seen in patients receiving stress ulcer prophylaxis (MHRD, 2.1%; 95% CI, 2.0%-2.2%; I2 = 0%), although this association was no longer found when 1 large study was removed in a sensitivity analysis. There was no statistically significant difference in length of PICU stay between the groups (standardized mean difference, 0.42 days; 95% CI, -0.16 to 1.01 days; I2 = 89.8%). CONCLUSIONS Stress ulcer prophylaxis does not show a clear benefit in reducing GI bleeding or length of PICU stay. Observational studies suggest an increased risk of NP and mortality with stress ulcer prophylaxis, which remains to be validated in clinical trials.
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Translating the European Society for Clinical Nutrition and Metabolism 2019 guidelines into practice.
Reintam Blaser, A, Deane, AM, Starkopf, J
Current opinion in critical care. 2019;(4):314-321
Abstract
PURPOSE OF REVIEW To present a pragmatic approach to facilitate clinician's implementing the recent European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines on clinical nutrition in the intensive care unit. RECENT FINDINGS The ESPEN guidelines include 54 recommendations with a rationale for each recommendation. All data published since 1 January 2000 was reviewed and 31 meta-analyses were performed to inform these guidelines. An important aspect of the most recent ESPEN guidelines is an attempt to separate periods of critical illness into discrete - early acute, late acute and recovery - phases, with each exhibiting different metabolic profiles and requiring different strategies for nutritional and metabolic support. SUMMARY A pragmatic approach to incorporate the recent ESPEN guidelines into everyday clinical practice is provided.
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Association of obesity with morbidity and mortality in critically ill children: a systematic review and meta-analysis of observational studies.
Alipoor, E, Hosseinzadeh-Attar, MJ, Yaseri, M, Maghsoudi-Nasab, S, Jazayeri, S
International journal of obesity (2005). 2019;(4):641-651
Abstract
Recent studies have suggested that obesity might be protective in specific conditions such as critical illness; however, there are controversial data in critically ill children with obesity. The aim of this study was to investigate the association of obesity with mortality and other outcomes in these patients. We conducted a systematic review of observational studies investigating obesity in critically ill children, published by August 2017 in PubMed and Scopus. After screening documents, 15 articles with 142119 patients were included in the systematic review and meta-analysis. The results were reported with odds ratio (OR) or standard mean difference (SMD). The primary outcome was mortality and the secondary outcomes were length of ICU stay (ICU LOS), length of hospital stay (hospital LOS), and duration of mechanical ventilation (MV). The analysis showed that critically ill children without obesity had lower risk of mortality compared to patients with obesity (OR 0.79, 95% CI 0.64 to 0.97, P = 0.025, I2 = 35.2%). Hospital LOS was also significantly lower in children without obesity (pooled SMD -0.12, 95% CI -0.21 to -0.04, P = 0.004, I2 = 8.1%). There were no differences in ICU LOS (95% CI -0.19 to 0.01, P = 0.083) and duration of MV (95% CI -0.22 to 0.03, P = 0.136) between critically ill children with and without obesity. In conclusion, the current systematic review and meta-analysis revealed that critically ill children with obesity have higher risk of mortality and length of hospital stay compared to the group without obesity. Further prospective studies are essential to elucidate the role of obesity and underlying mechanisms in predicting outcomes of critically ill children.
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Early enteral nutrition (within 48 hours) versus delayed enteral nutrition (after 48 hours) with or without supplemental parenteral nutrition in critically ill adults.
Fuentes Padilla, P, Martínez, G, Vernooij, RW, Urrútia, G, Roqué I Figuls, M, Bonfill Cosp, X
The Cochrane database of systematic reviews. 2019;(10)
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Abstract
BACKGROUND Early enteral nutrition support (within 48 hours of admission or injury) is frequently recommended for the management of patients in intensive care units (ICU). Early enteral nutrition is recommended in many clinical practice guidelines, although there appears to be a lack of evidence for its use and benefit. OBJECTIVES To evaluate the efficacy and safety of early enteral nutrition (initiated within 48 hours of initial injury or ICU admission) versus delayed enteral nutrition (initiated later than 48 hours after initial injury or ICU admission), with or without supplemental parenteral nutrition, in critically ill adults. SEARCH METHODS We searched CENTRAL (2019, Issue 4), MEDLINE Ovid (1946 to April 2019), Embase Ovid SP (1974 to April 2019), CINAHL EBSCO (1982 to April 2019), and ISI Web of Science (1945 to April 2019). We also searched Turning Research Into Practice (TRIP), trial registers (ClinicalTrials.gov, ISRCTN registry), and scientific conference reports, including the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism. We applied no restrictions by language or publication status. SELECTION CRITERIA We included all randomized controlled trials (RCTs) that compared early versus delayed enteral nutrition, with or without supplemental parenteral nutrition, in adults who were in the ICU for longer than 72 hours. This included individuals admitted for medical, surgical, and trauma diagnoses, and who required any type of enteral nutrition. DATA COLLECTION AND ANALYSIS Two review authors extracted study data and assessed the risk of bias in the included studies. We expressed results as risk ratios (RR) for dichotomous data, and as mean differences (MD) for continuous data, both with 95% confidence intervals (CI). We assessed the certainty of the evidence using GRADE. MAIN RESULTS We included seven RCTs with a total of 345 participants. Outcome data were limited, and we judged many trials to have an unclear risk of bias in several domains. Early versus delayed enteral nutrition Six trials (318 participants) assessed early versus delayed enteral nutrition in general, medical, and trauma ICUs in the USA, Australia, Greece, India, and Russia. Primary outcomes Five studies (259 participants) measured mortality. It is uncertain whether early enteral nutrition affects the risk of mortality within 30 days (RR 1.00, 95% CI 0.16 to 6.38; 1 study, 38 participants; very low-quality evidence). Four studies (221 participants) reported mortality without describing the timeframe; we did not pool these results. None of the studies reported a clear difference in mortality between groups. Three studies (156 participants) reported infectious complications. We were unable to pool the results due to unreported data and substantial clinical heterogeneity. The results were inconsistent across studies. One trial measured feed intolerance or gastrointestinal complications; it is uncertain whether early enteral nutrition affects this outcome (RR 0.84, 95% CI 0.35 to 2.01; 59 participants; very low-quality evidence). Secondary outcomes One trial assessed hospital length of stay and reported a longer stay in the early enteral group (median 15 days (interquartile range (IQR) 9.5 to 20) versus 12 days (IQR 7.5 to15); P = 0.05; 59 participants; very low-quality evidence). Three studies (125 participants) reported the duration of mechanical ventilation. We did not pool the results due to clinical and statistical heterogeneity. The results were inconsistent across studies. It is uncertain whether early enteral nutrition affects the risk of pneumonia (RR 0.77, 95% CI 0.55 to 1.06; 4 studies, 192 participants; very low-quality evidence). Early enteral nutrition with supplemental parenteral nutrition versus delayed enteral nutrition with supplemental parenteral nutrition We identified one trial in a burn ICU in the USA (27 participants). Primary outcomes It is uncertain whether early enteral nutrition with supplemental parenteral nutrition affects the risk of mortality (RR 0.74, 95% CI 0.25 to 2.18; very low-quality evidence), or infectious complications (MD 0.00, 95% CI -1.94 to 1.94; very low-quality evidence). There were no data available for feed intolerance or gastrointestinal complications. Secondary outcomes It is uncertain whether early enteral nutrition with supplemental parenteral nutrition reduces the duration of mechanical ventilation (MD 9.00, 95% CI -10.99 to 28.99; very low-quality evidence). There were no data available for hospital length of stay or pneumonia. AUTHORS' CONCLUSIONS Due to very low-quality evidence, we are uncertain whether early enteral nutrition, compared with delayed enteral nutrition, affects the risk of mortality within 30 days, feed intolerance or gastrointestinal complications, or pneumonia. Due to very low-quality evidence, we are uncertain if early enteral nutrition with supplemental parenteral nutrition compared with delayed enteral nutrition with supplemental parenteral nutrition reduces mortality, infectious complications, or duration of mechanical ventilation. There is currently insufficient evidence; there is a need for large, multicentred studies with rigorous methodology, which measure important clinical outcomes.
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Chinese guidelines for the assessment and provision of nutrition support therapy in critically ill children.
Zhu, XM, Qian, SY, Lu, GP, Xu, F, Wang, Y, Liu, CF, Ren, XX, Zhang, YC, Gao, HM, Zhou, T, et al
World journal of pediatrics : WJP. 2018;(5):419-428
Abstract
BACKGROUND This document represents the first evidence-based guidelines to describe best practices in nutrition therapy in critically ill children (> 1 month and < 18 years), who are expected to require a length of stay more than 2 or 3 days in a Pediatric Intensive Care Unit admitting medical patients domain. METHODS A total of 25,673 articles were scanned for relevance. After careful review, 88 studies appeared to answer the pre-identified questions for the guidelines. We used the grading of recommendations, assessment, development and evaluation criteria to adjust the evidence grade based on the quality of design and execution of each study. RESULTS The guidelines emphasise the importance of nutritional assessment, particularly the detection of malnourished patients. Indirect calorimetry (IC) is recommended to estimate energy expenditure and there is a creative value in energy expenditure, 50 kcal/kg/day for children aged 1-8 years during acute phase if IC is unfeasible. Enteral nutrition (EN) and early enteral nutrition remain the preferred routes for nutrient delivery. A minimum protein intake of 1.5 g/kg/day is suggested for this patient population. The role of supplemental parenteral nutrition (PN) has been highlighted in patients with low nutritional risk, and a delayed approach appears to be beneficial in this group of patients. Immune-enhancing cannot be currently recommended neither in EN nor PN. CONCLUSION Overall, the pediatric critically ill population is heterogeneous, and an individualized nutrition support with the aim of improving clinical outcomes is necessary and important.
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Diaphragm and Lung Ultrasound to Predict Weaning Outcome: Systematic Review and Meta-Analysis.
Llamas-Álvarez, AM, Tenza-Lozano, EM, Latour-Pérez, J
Chest. 2017;(6):1140-1150
Abstract
BACKGROUND Deciding the optimal timing for extubation in patients who are mechanically ventilated can be challenging, and traditional weaning predictor tools are not very accurate. The aim of this systematic review and meta-analysis was to assess the accuracy of lung and diaphragm ultrasound for predicting weaning outcomes in critically ill adults. METHODS MEDLINE, the Cochrane Library, Web of Science, Scopus, LILACS, Teseo, Tesis Doctorales en Red, and OpenGrey were searched, and the bibliographies of relevant studies were reviewed. Two researchers independently selected studies that met the inclusion criteria and assessed study quality in accordance with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The summary receiver-operating characteristic curve and pooled diagnostic OR (DOR) were estimated by using a bivariate random effects analysis. Sources of heterogeneity were explored by using predefined subgroup analyses and bivariate meta-regression. RESULTS Nineteen studies involving 1,071 people were included in the study. For diaphragm thickening fraction, the area under the summary receiver-operating characteristic curve was 0.87, and DOR was 21 (95% CI, 11-40). Regarding diaphragmatic excursion, pooled sensitivity was 75% (95% CI, 65-85); pooled specificity, 75% (95% CI, 60-85); and DOR, 10 (95% CI, 4-24). For lung ultrasound, the area under the summary receiver-operating characteristic curve was 0.77, and DOR was 38 (95% CI, 7-198). Based on bivariate meta-regression analysis, a significantly higher specificity for diaphragm thickening fraction and higher sensitivity for diaphragmatic excursion was detected in studies with applicability concerns. CONCLUSIONS Lung and diaphragm ultrasound can help predict weaning outcome, but its accuracy may vary depending on the patient subpopulation.
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Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines.
Reintam Blaser, A, Starkopf, J, Alhazzani, W, Berger, MM, Casaer, MP, Deane, AM, Fruhwald, S, Hiesmayr, M, Ichai, C, Jakob, SM, et al
Intensive care medicine. 2017;(3):380-398
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PURPOSE To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. METHODS We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. RESULTS We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. CONCLUSIONS We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.
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Underfeeding versus full enteral feeding in critically ill patients with acute respiratory failure: a systematic review with meta-analysis of randomized controlled trials.
Stuani Franzosi, O, Delfino von Frankenberg, A, Loss, SH, Silva Leite Nunes, D, Rios Vieira, SR
Nutricion hospitalaria. 2017;(1):19-29
Abstract
INTRODUCTION Although guidelines emphasize that the provision of enteral nutrition (EN) should be as close as the patient's needs, prospective studies question this strategy. OBJECTIVE To compare the effect of two EN strategies (underfeeding versus full-feeding) on ICU and overall mortality (hospital mortality or 60-day mortality) and length of stay (LOS), duration of mechanical ventilation (MV), infectious complications, and gastrointestional tolerability in ICU patients. METHODS Random effects meta-analysis of randomized controlled trials (RCT). Our search covered MEDLINE, EMBASE, SCOPUS and CENTRAL databases until May 2015. Underfeeding was assigned into to two different groups according to the level of energy intake achieved (moderate feeding 46-72% and trophic feeding 16-25%) for subgroup analysis. RESULTS Five RCTs were included among the 904 studies retrieved (n=2432 patients). No difference was found in overall mortality when all five studies were combined. In the subgroup analysis, moderate feeding (three studies) showed lower mortality compared with full-feeding (RR 0.82;95%CI,0.68-0.98;I2 0% p=0.59 for heterogeneity). No differences were found for ICU mortality, ICU and hospital LOS, duration of MV, and infectious complications. Underfeeding showed lower occurrence of GI signs and symptoms except for aspiration and abdominal distention. CONCLUSIONS This meta-analysis found no differences in ICU and overall mortality, ICU and hospital LOS, duration of MV, and infectious complications between underfeeding and full-feeding. The subgroup analysis showed lower overall mortality among patients receiving moderate underfeeding. This result should be cautiously interpreted due to the limitations of the small number of studies analyzed and their methodology.
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Vitamin D deficiency in critically ill children: a systematic review and meta-analysis.
McNally, JD, Nama, N, O'Hearn, K, Sampson, M, Amrein, K, Iliriani, K, McIntyre, L, Fergusson, D, Menon, K
Critical care (London, England). 2017;(1):287
Abstract
BACKGROUND Vitamin D deficiency (VDD) has been hypothesized not only to be common but also to represent a potentially modifiable risk factor for greater illness severity and clinical outcome during critical illness. The objective of this systematic review was to determine the frequency of VDD in pediatric critical illness and its association with clinical outcomes. METHODS MEDLINE, Embase, and CENTRAL were searched through December 12, 2016, with no date or language restrictions. The primary objective was to estimate the prevalence of VDD in the pediatric intensive care unit (PICU) and compare vitamin D status with healthy control populations. Secondary objectives were to evaluate whether VDD is associated with mortality, increased illness severity, PICU interventions, and patient clinical course. Random effects meta-analysis was used to calculate pooled VDD event rate, compare levels with those of control subjects, and evaluate for associations between VDD and clinical outcome. RESULTS Among 2700 citations, 17 studies meeting study eligibility were identified. The studies reported a total of 2783 critically ill children and had a median sample size of 120 (range 12-511). The majority of studies used a 25-hydroxyvitamin D [25(OH)D] level less than 50 nmol/L to define VDD, and the pooled VDD prevalence was 54.8 (95% CI 45.4-63.9). Average 25(OH)D levels were significantly lower in PICU patients than in healthy control subjects (pooled difference -17.3 nmol/L, 95% CI -14.0 to -20.6). In a meta-analysis calculation, we found that VDD was associated with increased mortality (OR 1.62, 95% CI 1.11-2.36), illness severity, and need for PICU interventions. CONCLUSIONS Approximately 50% of critically ill children have VDD at the time of PICU admission, defined as a blood total 25(OH)D concentration under 50 nmol/L. VDD was further determined to be associated with greater illness severity, multiple organ dysfunction, and mortality in the PICU setting. Clinical trials are required to determine if optimization of vitamin D status improves patient outcome. TRIAL REGISTRATION PROSPERO, CRD42016026617 . Registered on 11 January 2016.
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Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis.
Silversides, JA, Major, E, Ferguson, AJ, Mann, EE, McAuley, DF, Marshall, JC, Blackwood, B, Fan, E
Intensive care medicine. 2017;(2):155-170
Abstract
BACKGROUND It is unknown whether a conservative approach to fluid administration or deresuscitation (active removal of fluid using diuretics or renal replacement therapy) is beneficial following haemodynamic stabilisation of critically ill patients. PURPOSE To evaluate the efficacy and safety of conservative or deresuscitative fluid strategies in adults and children with acute respiratory distress syndrome (ARDS), sepsis or systemic inflammatory response syndrome (SIRS) in the post-resuscitation phase of critical illness. METHODS We searched Medline, EMBASE and the Cochrane central register of controlled trials from 1980 to June 2016, and manually reviewed relevant conference proceedings from 2009 to the present. Two reviewers independently assessed search results for inclusion and undertook data extraction and quality appraisal. We included randomised trials comparing fluid regimens with differing fluid balances between groups, and observational studies investigating the relationship between fluid balance and clinical outcomes. RESULTS Forty-nine studies met the inclusion criteria. Marked clinical heterogeneity was evident. In a meta-analysis of 11 randomised trials (2051 patients) using a random-effects model, we found no significant difference in mortality with conservative or deresuscitative strategies compared with a liberal strategy or usual care [pooled risk ratio (RR) 0.92, 95 % confidence interval (CI) 0.82-1.02, I 2 = 0 %]. A conservative or deresuscitative strategy resulted in increased ventilator-free days (mean difference 1.82 days, 95 % CI 0.53-3.10, I 2 = 9 %) and reduced length of ICU stay (mean difference -1.88 days, 95 % CI -0.12 to -3.64, I 2 = 75 %) compared with a liberal strategy or standard care. CONCLUSIONS In adults and children with ARDS, sepsis or SIRS, a conservative or deresuscitative fluid strategy results in an increased number of ventilator-free days and a decreased length of ICU stay compared with a liberal strategy or standard care. The effect on mortality remains uncertain. Large randomised trials are needed to determine optimal fluid strategies in critical illness.