Abstract

BACKGROUND To develop a risk prediction model for the occurrence of severe acute kidney injury (AKI) in intensive care unit (ICU) patients receiving fluid resuscitation. METHODS We conducted a secondary analysis of the Crystalloid vs. Hydroxyethyl Starch Trial (CHEST) trial, a blinded randomized controlled trial that enrolled ICU patients who received intravenous fluid resuscitation. The primary outcome was the first event in a composite outcome of doubling of serum creatinine and/or treatment with renal replacement treatment (RRT) within 28 days of randomization. The final model developed using multivariable logistic regression with backwards elimination was validated internally and then translated into a predictive equation. RESULTS Six thousand seven hundred twenty-seven ICU participants were studied, among whom 745 developed the study outcome. The final model having six variables, including admission diagnosis of sepsis, illness severity score, mechanical ventilation, tachycardia, baseline estimated glomerular filtration rate and emergency admission. The model had good discrimination (c-statistic = 0.72, 95% confidence interval 0.697-0.736) and calibration (Hosmer-Lemeshow test, χ(2) = 14.4, p = 0.07) for the composite outcome, with a c-statistic after internal bootstrapping validation of 0.72, which revealed a low degree of over-fitting. The positive predictive value and negative predictive value were 58.8 and 89.1%, respectively. The decision curve analysis indicates a net benefit in prediction of severe AKI using the model across a range of threshold probabilities between 5 and 35%. CONCLUSIONS Our model, using readily available clinical variables to identify ICU patients at high risk of severe AKI achieved good predictive performance in a clinically relevant population.

Abstract

OBJECTIVES Pit crew models are designed to improve teamwork in critical medical situations, like advanced life support (ALS). We investigated if a pit crew model training improves performance assessment and ALS skills retention when compared to standard ALS education. METHODS This was a prospective, blinded, randomized, and controlled, parallel-group trial. We recruited students to 4-person resuscitation teams. We video recorded simulated ALS-situations after the ALS education and after 6-month follow-up. We analyzed technical skills (TS) and non-technical skills (NTS) demonstrated in them with an instrument measuring TS and NTS, and used a linear mixed model to model the difference between the groups in the TS and NTS. Another linear model was used to explore the difference between the groups in hands-on ratio and hands-free time. The difference in the total assessment score was analyzed with the Mann-Whitney U-test. The primary outcome was the difference in the total assessment score between the groups at follow-up. ALS skills were considered to be a secondary outcome. RESULTS Twenty-six teams underwent randomization. Twenty-two teams received the allocated education. Fifteen teams were evaluated at 6-month follow-up: 7 in the intervention group and 8 in the control group. At 6-month follow-up, the median (Q(1)-Q(3)) total assessment score for the control group was 6.5 (6-8) and 7 (6.25-8) for the intervention group but the difference was not significant (U = 133, P = 0.373). The intervention group performed better in terms of chest compression quality (interaction term, β3 = 0.23; 95% confidence interval, 0.01-0.50; P = 0.043) at follow-up. CONCLUSION We found no difference in overall performance between the study arms. However, trends indicate that the pit crew model may help to retain ALS skills in different areas like chest compression quality.

Abstract

OBJECTIVES Transfusion with washed packed red blood cells (PRBCs) may be associated with reduced transfusion-related pro-inflammatory cytokine production. This may be because of alterations in recipient immune responses. METHODS This randomised trial evaluated the effect of transfusion with washed compared with unwashed PRBCs on pro-inflammatory cytokines and endothelial activation in 154 preterm newborns born before 29 weeks' gestation. Changes in plasma cytokines and measures of endothelial activation in recipient blood were analysed after each of the first three transfusions. RESULTS By the third transfusion, infants receiving unwashed blood had an increase in IL-17A (P = 0.04) and TNF (P = 0.007), whereas infants receiving washed blood had reductions in IL-17A (P = 0.013), TNF (P = 0.048), IL-6 (P = 0.001), IL-8 (P = 0.037), IL-12 (P = 0.001) and IFN-γ (P = 0.001). The magnitude of the post-transfusion increase in cytokines did not change between the first and third transfusions in the unwashed group but decreased in the washed group for IL-12 (P = 0.001), IL-17A (P = 0.01) and TNF (P = 0.03), with the difference between the groups reaching significance by the third transfusion (P < 0.001 for each cytokine). CONCLUSION The pro-inflammatory immune response to transfusion in preterm infants can be modified when PRBCs are washed prior to transfusion. Further studies are required to determine whether the use of washed PRBCs for neonatal transfusion translates into reduced morbidity and mortality.

Abstract

OBJECTIVES Extracorporeal membrane oxygenation (ECMO) involves complex coagulation management and frequent hemostatic complications. ECMO practice between centers is variable. To compare results between coagulation studies, standardized definitions and clear documentation of ECMO practice is essential. We assessed how study population, outcome definitions, and ECMO-, coagulation-, and transfusion-related parameters were described in pediatric ECMO studies. DATA SOURCES Embase, Medline, Web of Science, Cochrane Library and Google Scholar. STUDY SELECTION English original studies of pediatric ECMO patients describing hemostatic tests or outcome. DATA EXTRACTION Eligibility was assessed following PRISMA guidelines. Study population, outcome and ECMO-, coagulation, and transfusion parameters were summarized. DATA SYNTHESIS A total of 107 of 1312 records were included. Study population parameters most frequently included (gestational) age (79%), gender (60%), and (birth) weight (59%). Outcomes, including definitions of bleeding (29%), thrombosis (15%), and survival (43%), were described using various definitions. Description of pump type, oxygenator and cannulation mode occurred in 49%, 45%, and 36% of studies, respectively. The main coagulation test (53%), its reference ranges (49%), and frequency of testing (24%) were the most prevalent reported coagulation parameters. The transfusion thresholds for platelets, red blood cells, and fibrinogen were described in 27%, 18%, and 18% of studies, respectively. CONCLUSIONS This systematic review demonstrates a widespread lack of detail or standardization of several parameters in coagulation research of pediatric ECMO patients. We suggest several parameters that might be included in future coagulation studies. We encourage the ECMO community to adopt and refine this list of parameters and to use standardized definitions in future research.

Abstract

Background: Anemia remains a common comorbidity of preterm infants in the neonatal intensive care unit (NICU). Left untreated, severe anemia may adversely affect organ function due to inadequate oxygen supply to meet oxygen requirements, resulting in hypoxic tissue injury, including cerebral tissue. To prevent hypoxic tissue injury, anemia is generally treated with packed red blood cell (RBC) transfusions. Previously published data raise concerns about the impact of anemia on cerebral oxygen delivery and, therefore, on neurodevelopmental outcome (NDO). Objective: To provide a systematic overview of the impact of anemia and RBC transfusions during NICU admission on cerebral oxygenation, measured using near-infrared spectroscopy (NIRS), brain injury and development, and NDO in preterm infants. Data Sources: PubMed, Embase, reference lists. Study Selection: We conducted 3 different searches for English literature between 2000 and 2020; 1 for anemia, RBC transfusions, and cerebral oxygenation, 1 for anemia, RBC transfusions, and brain injury and development, and 1 for anemia, RBC transfusions, and NDO. Data Extraction: Two authors independently screened sources and extracted data. Quality of case-control studies or cohort studies, and RCTs was assessed using either the Newcastle-Ottawa Quality Assessment Scale or the Van Tulder Scale, respectively. Results: Anemia results in decreased oxygen-carrying capacity, worsening the burden of cerebral hypoxia in preterm infants. RBC transfusions increase cerebral oxygenation. Improved brain development may be supported by avoidance of cerebral hypoxia, although restrictive RBC transfusion strategies were associated with better long-term neurodevelopmental outcomes. Conclusions: This review demonstrated that anemia and RBC transfusions were associated with cerebral oxygenation, brain injury and development and NDO in preterm infants. Individualized care regarding RBC transfusions during NICU admission, with attention to cerebral tissue oxygen saturation, seems reasonable and needs further investigation to improve both short-term effects and long-term neurodevelopment of preterm infants.

Abstract

BACKGROUND Dynamic arterial elastance (Ea(dyn)) has been extensively considered as a functional parameter of arterial load. However, conflicting evidence has been obtained on the ability of Ea(dyn) to predict mean arterial pressure (MAP) changes after fluid expansion. This meta-analysis sought to assess the predictive performance of Ea(dyn) for the MAP response to fluid expansion in mechanically ventilated hypotensive patients. METHODS We systematically searched electronic databases through November 28, 2020, to retrieve studies that evaluated the association between Ea(dyn) and fluid expansion-induced MAP increases in mechanically ventilated hypotensive adults. Given the diverse threshold value of Ea(dyn) among the studies, we only reported the area under the hierarchical summary receiver operating characteristic curve (AUHSROC) as the primary measure of diagnostic accuracy. RESULTS Eight observational studies that included 323 patients with 361 fluid expansions met the eligibility criteria. The results showed that Ea(dyn) was a good predictor of MAP increases in response to fluid expansion, with an AUHSROC of 0.92 [95% confidence interval (CI) 0.89 to 0.94]. Six studies reported the cut-off value of Ea(dyn), which ranged from 0.65 to 0.89. The cut-off value of Ea(dyn) was nearly conically symmetrical, most data were centred between 0.7 and 0.8, and the mean and median values were 0.77 and 0.75, respectively. The subgroup analyses indicated that the AUHSROC was slightly higher in the intensive care unit (ICU) patients (0.96; 95% CI 0.94 to 0.98) but lower in the surgical patients in the operating room (0.72; 95% CI 0.67 to 0.75). The results indicated that the fluid type and measurement technique might not affect the diagnostic accuracy of Ea(dyn). Moreover, the AUHSROC for the sensitivity analysis of prospective studies was comparable to that in the primary analysis. CONCLUSIONS Ea(dyn) exhibits good performance for predicting MAP increases in response to fluid expansion in mechanically ventilated hypotensive adults, especially in the ICU setting.

Abstract

OBJECTIVE We aimed to determine whether the restrictive red-cell transfusion strategy was superior to the liberal one in reducing all-cause mortality in critically ill adults. METHODS The MEDLINE, EMBASE, PubMed, Web of Science, and Cochrane Library Central Register of Controlled Trials databases were searched from inception to January 2019 to identify meta-analyses or systematic reviews and published randomized controlled trials which were restrictive versus liberal blood transfusion with mortality as the endpoint in critically ill adults. We used two search routes whereby one search was restricted to systematic reviews, reviews, or meta-analysis, and the other was not restricted. There were no date restrictions, but language was limited to English and the population was restricted to critically ill adults. The data of study methods, participant characteristics, and outcomes were extracted and analyzed independently by 2 reviewers. The main outcome was all-cause mortality. RESULTS Through screening the obtained records, we enrolled 7 randomized clinical trials that included information on restrictive versus liberal red-cell transfusion and mortality of intensive care unit (ICU) patients. Involving a total of 7,363 ICU adult patients, ICU mortality (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.62, 1.08, p = 0.15), 28/30-day mortality (RR 0.98, 95% CI 0.84, 1.13, p = 0.74), 60-day mortality (RR 1.01, 95% CI 0.87, 1.16, p = 0.91), 90-day mortality (RR 1.02, 95% CI 0.92, 1.14, p = 0.69), 120-day mortality (RR 1.29, 95% CI 0.67, 2.47, p = 0.44), and 180-day mortality (RR 0.91, 95% CI 0.75, 1.12, p = 0.38) were not statistically significantly different when the restrictive transfusion strategy was compared with the liberal transfusion strategy. However, we surprisingly discovered that 112 out of 469 (24%) patients who received a unit RBC transfusion when hemoglobin was less than 7 g/dL, and 142 out of 469 (30.3%) who received a unit of RBC transfused with hemoglobin less than 9 g/dL, had died during hospitalization (RR 0.79, 95% CI 0.64, 0.97, p = 0.03). The results showed that the restrictive transfusion strategy could decrease in-hospital mortality compared with the liberal transfusion strategy. It was safe to utilize a restrictive transfusion threshold of less than 7 g/dL in stable critically ill adults. CONCLUSIONS In this study, we found that the restrictive red-cell transfusion strategy potentially reduced in-hospital mortality in critically ill adults with anemia compared with the liberal strategy.

Abstract

OBJECTIVE To summarize the evidence comparing various balanced crystalloid solutions. DATA SOURCES We searched MEDLINE, EMBASE, PUBMED, and CENTRAL databases. STUDY SELECTION We included randomized controlled trials that directly compared the IV administration of one balanced crystalloid solution with another. DATA EXTRACTION AND ANALYSIS We examined metabolic and patient-important outcomes and conducted meta-analysis using random effects model. For comparisons or outcomes with insufficient data to allow for pooling, we describe results narratively. We assessed risk of bias for individual trials using the Cochrane risk of bias tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations methodology. DATA SYNTHESIS We included 24 randomized controlled trials comparing Plasmalyte, Ringer's Lactate, Ringerfundin, Hartmann's solution, Ringer's Bicarbonate, Sterofundin, Kabilyte, Normosol, and novel balanced solutions. Of the included studies, 16 were performed in the perioperative setting, six in the ICU, one in the emergency department, and one in healthy volunteers. Administration of Plasmalyte resulted in a lower postinfusion serum chloride concentration (mean difference, 0.83 mmol/L lower; 95% CI, 0.03-1.64 mmol/L lower, low certainty), higher postinfusion base excess (mean difference, 0.65 mmol/L higher, 95% CI, 0.25-1.05 mmol/L higher, low certainty), and lower postinfusion serum lactate levels (mean difference, 0.46 mmol/L lower; 95% CI, 0.05-0.87 mmol/L lower, low certainty) compared with administration of any other balanced crystalloid. There were no important differences in postinfusion serum pH or potassium when comparing Plasmalyte with other balanced crystalloids. Data addressing other comparisons or examining the impact of different balanced crystalloids on patient-important outcomes were sparsely reported and too heterogeneous to allow for pooling. CONCLUSIONS Administration of Plasmalyte results in lower serum concentrations of chloride and lactate, and higher base excess than other balanced crystalloids. The certainty of evidence is low and requires further study in large randomized controlled trials to inform the choice of balanced crystalloid in patients requiring volume replacement.

Abstract

OBJECTIVES Patients with severe spontaneous intracranial haemorrhages, managed in intensive care units, face ethical issues regarding the difficulty of anticipating their recovery. Prognostic tools help clinicians in counselling patients and relatives and guide therapeutic decisions. We aimed to methodologically assess prognostic tools for functional outcomes in severe spontaneous intracranial haemorrhages. DATA SOURCES Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, we conducted a systematic review querying Medline, Embase, Web of Science, and the Cochrane in January 2020. STUDY SELECTION We included development or validation of multivariate prognostic models for severe intracerebral or subarachnoid haemorrhage. DATA EXTRACTION We evaluated the articles following the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies and Transparent Reporting of multivariable prediction model for Individual Prognosis Or Diagnosis statements to assess the tools' methodological reporting. RESULTS Of the 6149 references retrieved, we identified 85 articles eligible. We discarded 43 articles due to the absence of prognostic performance or predictor selection. Among the 42 articles included, 22 did not validate models, 6 developed and validated models and 14 only externally validated models. When adding 11 articles comparing developed models to existing ones, 25 articles externally validated models. We identified methodological pitfalls, notably the lack of adequate validations or insufficient performance levels. We finally retained three scores predicting mortality and unfavourable outcomes: the IntraCerebral Haemorrhages (ICH) score and the max-ICH score for intracerebral haemorrhages, the SubArachnoid Haemorrhage International Trialists score for subarachnoid haemorrhages. CONCLUSIONS Although prognostic studies on intracranial haemorrhages abound in the literature, they lack methodological robustness or show incomplete reporting. Rather than developing new scores, future authors should focus on externally validating and updating existing scores with large and recent cohorts.

Abstract

BACKGROUND Intraventricular hemorrhage (IVH) is a common complication in preterm infants that has poor outcomes, especially in severe cases, and there are currently no widely accepted effective treatments. Erythropoietin has been shown to be neuroprotective in neonatal brain injury. OBJECTIVE The objective of this study was to evaluate the protective effect of repeated low-dose recombinant human erythropoietin (rhEPO) in preterm infants with IVH. METHODS This was a single-blinded prospective randomized controlled trial. Preterm infants ≤ 32 weeks gestational age who were diagnosed with IVH within 72 h after birth were randomized to receive rhEPO 500 IU/kg or placebo (equivalent volume of saline) every other day for 2 weeks. The primary outcome was death or neurological disability assessed at 18 months of corrected age. RESULTS A total of 316 eligible infants were included in the study, with 157 in the rhEPO group and 159 in the placebo group. Although no significant differences in mortality (p = 0.176) or incidence of neurological disability (p = 0.055) separately at 18 months of corrected age were seen between the rhEPO and placebo groups, significantly fewer infants had poor outcomes (death and neurological disability) in the rhEPO group: 14.9 vs. 26.4%; odds ratio (OR) 0.398; 95% confidence interval (CI) 0.199-0.796; p = 0.009. In addition, the incidence of Mental Development Index scores of < 70 was lower in the rhEPO group than in the placebo group: 7.2 vs. 15.3%; OR 0.326; 95% CI 0.122-0.875; p = 0.026. CONCLUSIONS Treatment with repeated low-dose rhEPO improved outcomes in preterm infants with IVH. TRIAL REGISTRATION The study was retrospectively registered on ClinicalTrials.gov on 16 April 2019 (NCT03914690).