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BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).
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Anemia , Lesiones Traumáticas del Encéfalo , Transfusión de Eritrocitos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anemia/sangre , Anemia/etiología , Anemia/terapia , Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/terapia , Enfermedad Crítica , Depresión/etiología , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/métodos , Escala de Consecuencias de Glasgow , Hemoglobinas/análisis , Calidad de VidaRESUMEN
BACKGROUND: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).
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Ácido Ascórbico , Sepsis , Adulto , Ácido Ascórbico/efectos adversos , Humanos , Hipoglucemiantes/uso terapéutico , Unidades de Cuidados Intensivos , Insuficiencia Multiorgánica , Calidad de Vida , Sepsis/tratamiento farmacológico , Vasoconstrictores/efectos adversos , Vitaminas/efectos adversosRESUMEN
Rationale: Sepsis management relies on fluid resuscitation avoiding fluid overload and its related organ congestion. Objectives: To explore the influence of country income group on risk-benefit balance of fluid management strategies in sepsis. Methods: We searched e-databases for all randomized controlled trials on fluid resuscitation in patients with sepsis or septic shock up to January 2023, excluding studies on hypertonic fluids, colloids, and depletion-based interventions. The effect of fluid strategies (higher versus lower volumes) on mortality was analyzed per income group (i.e., low- and middle-income countries [LMICs] or high-income countries [HICs]). Measurements and Main Results: Twenty-nine studies (11,798 patients) were included in the meta-analysis. There was a numerically higher mortality in studies of LMICs as compared with those of HICs: median, 37% (interquartile range [IQR]: 26-41) versus 29% (IQR: 17-38; P = 0.06). Income group significantly interacted with the effect of fluid volume on mortality: Higher fluid volume was associated with higher mortality in LMICs but not in HICs: odds ratio (OR), 1.47; 95% confidence interval (95% CI): 1.14-1.90 versus 1.00 (95% CI: 0.87-1.16), P = 0.01 for subgroup differences. Higher fluid volume was associated with increased need for mechanical ventilation in LMICs (OR, 1.24 [95% CI: 1.08-1.43]) but not in HICs (OR, 1.02 [95% CI: 0.80-1.29]). Self-reported access to mechanical ventilation also significantly influenced the effect of fluid volume on mortality, which increased with higher volumes only in settings with limited access to mechanical ventilation (OR: 1.45 [95% CI: 1.09-1.93] vs. 1.09 [95% CI: 0.93-1.28], P = 0.02 for subgroup differences). Conclusions: In sepsis trials, the effect of fluid resuscitation approach differed by setting, with higher volume of fluid resuscitation associated with increased mortality in LMICs and in settings with restricted access to mechanical ventilation. The precise reason for these differences is unclear and may be attributable in part to resource constraints, participant variation between trials, or other unmeasured factors.
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Sepsis , Choque Séptico , Humanos , Bases de Datos Factuales , Fluidoterapia , Renta , Sepsis/terapia , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain. METHODS: We conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients were randomly assigned to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or acute kidney injury persisted for >72 hours). The primary outcome was death from any cause at 90 days. RESULTS: Of the 3019 patients who had undergone randomization, 2927 (97.0%) were included in the modified intention-to-treat analysis (1465 in the accelerated-strategy group and 1462 in the standard-strategy group). Of these patients, renal-replacement therapy was performed in 1418 (96.8%) in the accelerated-strategy group and in 903 (61.8%) in the standard-strategy group. At 90 days, death had occurred in 643 patients (43.9%) in the accelerated-strategy group and in 639 (43.7%) in the standard-strategy group (relative risk, 1.00; 95% confidence interval [CI], 0.93 to 1.09; P = 0.92). Among survivors at 90 days, continued dependence on renal-replacement therapy was confirmed in 85 of 814 patients (10.4%) in the accelerated-strategy group and in 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 to 2.43). Adverse events occurred in 346 of 1503 patients (23.0%) in the accelerated-strategy group and in 245 of 1489 patients (16.5%) in the standard-strategy group (P<0.001). CONCLUSIONS: Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy. (Funded by the Canadian Institutes of Health Research and others; STARRT-AKI ClinicalTrials.gov number, NCT02568722.).
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Lesión Renal Aguda/terapia , Terapia de Reemplazo Renal , Lesión Renal Aguda/mortalidad , Anciano , Enfermedad Crítica/terapia , Humanos , Análisis de Intención de Tratar , Persona de Mediana Edad , Terapia de Reemplazo Renal/efectos adversos , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
OBJECTIVES: The Lessening Organ Dysfunction with Vitamin C trial showed a harmful effect of vitamin C on 28-day death or persistent organ dysfunction. To maximize interpretation, we present a post hoc Bayesian reanalysis. DESIGN: Bayesian reanalysis of a randomized placebo-controlled trial. SETTING: Thirty-five ICUs. PATIENTS: Adults with proven or suspected infection, vasopressor support, and no more than 24 hours of ICU admission. INTERVENTIONS: Patients were allocated to receive either vitamin C (50 mg/kg of body weight) or placebo every 6 hours for up to 96 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the composite of death or persistent organ dysfunction (i.e., vasopressor use, invasive mechanical ventilation, or new renal replacement therapy) at 28 days. We used Bayesian log-binomial models with random effects for hospital site and varying informative prior beliefs for the effect of vitamin C to estimate risk ratios (RRs) with 95% credible intervals (Crls) in the intention to treat population (vitamin C, 435 patients; placebo, 437 patients). Using weakly neutral priors, patients allocated to vitamin C had a higher risk of death or persistent organ dysfunction at 28 days (RR, 1.20; 95% Crl, 1.04-1.39; probability of harm, 99%). This effect was consistent when using optimistic (RR, 1.14; 95% Crl, 1.00-1.31; probability of harm, 98%) and empiric (RR, 1.09; 95% Crl, 0.97-1.22; probability of harm, 92%) priors. Patients allocated to vitamin C also had a higher risk of death at 28 days under weakly neutral (RR, 1.17; 95% Crl, 0.98-1.40; probability of harm, 96%), optimistic (RR, 1.10; 95% Crl, 0.94-1.30; probability of harm, 88%), and empiric (RR, 1.05; 95% Crl, 0.92-1.19; probability of harm, 76%) priors. CONCLUSIONS: The use of vitamin C in adult patients with proven or suspected infection and vasopressor support is associated with high probability of harm.
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Sepsis , Vitaminas , Humanos , Adulto , Ácido Ascórbico/uso terapéutico , Insuficiencia Multiorgánica/complicaciones , Teorema de Bayes , Sepsis/tratamiento farmacológico , Sepsis/complicacionesRESUMEN
OBJECTIVE: Extubation failure in brain-injured patients is associated with increased morbidity. Our objective was to systematically review prognostic factors associated with extubation failure in acutely brain-injured adult patients receiving invasive ventilation in an ICU. DATA SOURCES: MEDLINE, Embase, and Cochrane Central were searched from inception to January 31, 2022. STUDY SELECTION: Two reviewers independently screened citations and selected English-language cohort studies and randomized trials examining the association of prognostic factors with extubation failure. Studies were considered if they included greater than or equal to 80% adult patients with acute brain injury admitted to the ICU and mechanically ventilated for greater than or equal to 24 hours. DATA EXTRACTION: Two reviewers extracted data on population, prognostic factors, extubation outcomes, and risk of bias (using the quality in prognostic factors tool). DATA SYNTHESIS: In the primary analysis, adjusted odds ratios (aOR) for each prognostic factor were pooled using random-effects models. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. The search identified 7,626 citations, of which 21 studies met selection criteria. Moderate-certainty evidence suggested increased risk of extubation failure with older age (aOR, 3.0 for upper vs lower tertile; 95% CI, 1.78-5.07) and longer duration of mechanical ventilation (aOR, 3.47 for upper vs lower tertile; 95% CI, 1.68-7.19). Presence of cough (aOR, 0.40; 95% CI, 0.28-0.57) and intact swallow (aOR, 0.34; 95% CI, 0.21-0.54) probably decreased risk of extubation failure (moderate certainty). Associations of other factors with extubation failure were informed by low or very low certainty evidence. CONCLUSIONS: Patient age, duration of mechanical ventilation, and airway reflexes were associated with extubation failure in brain-injured patients with moderate certainty. Future studies are needed to determine the optimal application of these variables in clinical practice.
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Extubación Traqueal , Respiración Artificial , Adulto , Humanos , Pronóstico , Respiración Artificial/efectos adversos , Intubación , EncéfaloRESUMEN
OBJECTIVES: Balancing the risks of hypotension and vasopressor-associated adverse effects is a daily challenge in ICUs. We conducted a systematic review with meta-analysis to examine the effect of lower versus higher exposure to vasopressor therapy on mortality among adult ICU patients with vasodilatory hypotension. DATA SOURCES: We searched Ovid Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies published from inception to October 15, 2021. STUDY SELECTION: We included randomized controlled trials of lower versus higher exposure to vasopressor therapy in adult ICU patients with vasodilatory hypotension without language or publication status limits. DATA EXTRACTION: The primary outcome was 90-day all-cause mortality, with seven prespecified subgroups. Secondary outcomes included shorter- and longer-term mortality, use of life-sustaining therapies, vasopressor-related complications, neurologic outcome, and quality of life at longest reported follow-up. We conducted random-effects meta-analyses to calculate summary effect measures across individual studies (risk ratio [RR] for dichotomous variables, mean difference for continuous variables, both with 95% CIs). The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. We registered this review on the International Prospective Register of Systematic Reviews (CRD42021224434). DATA SYNTHESIS: Of 3,403 records retrieved, 68 full-text articles were reviewed and three eligible studies included. Lower exposure to vasopressors probably lowers 90-day mortality but this is based on moderate-certainty evidence, lowered for imprecision (RR, 0.94; 95% CI, 0.87-1.02). There was no credible subgroup effect. Lower vasopressor exposure may also decrease the risk of supraventricular arrhythmia (odds ratio, 0.55; 95% CI, 0.36-0.86; low certainty). CONCLUSIONS: In patients with vasodilatory hypotension who are started on vasopressors, moderate-certainty evidence from three randomized trials showed that lower vasopressor exposure probably lowers mortality. However, additional trial data are needed to reach an optimal information size to detect a clinically important 10% relative reduction in mortality with this approach.
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Hipotensión , Calidad de Vida , Adulto , Humanos , Hipotensión/inducido químicamente , Hipotensión/tratamiento farmacológicoRESUMEN
BACKGROUND: This Rapid Practice Guideline provides an evidence-based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy? METHODS: The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation approach, we evaluated the certainty of evidence and developed recommendations using the evidence-to-decision framework. We conducted an electronic vote, requiring >80% agreement among the panel for a recommendation to be adopted. RESULTS: At longest follow-up, 90 days, intravenous vitamin C probably does not substantially impact (relative risk 1.05, 95% confidence interval [CI] 0.94 to 1.17; absolute risk difference 1.8%, 95% CI -2.2 to 6.2; 6 trials, n = 2148, moderate certainty). Effects of vitamin C on mortality at earlier timepoints was of low or very low certainty due to risk of bias of the included studies and significant heterogeneity between study results. Few adverse events were reported with the use of vitamin C. The panel did not identify any major differences in other outcomes, including duration of mechanical ventilation, ventilator free days, hospital or intensive care unit length of stay, acute kidney injury, need for renal replacement therapy. Vitamin C may result in a slight reduction in duration of vasopressor support (MD -18.9 h, 95% CI -26.5 to -11.4; 21 trials, n = 2661, low certainty); but may not reduce sequential organ failure assessment scores (MD -0.69, 95% CI -1.55 to 0.71; 24 trials, n = 4002, low certainty). The panel judged the undesirable consequences of using IV vitamin C to probably outweigh the desirable consequences, and therefore issued a conditional recommendation against using IV vitamin C therapy in sepsis. CONCLUSIONS: The panel suggests against use of intravenous vitamin C in adult patients with sepsis, beyond that of standard nutritional supplementation. Small and single center trials on this topic should be discouraged.
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Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.
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Respiración con Presión Positiva , Síndrome de Dificultad Respiratoria , Adulto , Teorema de Bayes , Humanos , Pulmón , Metaanálisis en Red , Respiración con Presión Positiva/métodos , Síndrome de Dificultad Respiratoria/terapiaRESUMEN
Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain. Objective: To determine whether vitamin C improves outcomes for patients with COVID-19. Design, Setting, and Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents. Interventions: Patients were randomized to receive vitamin C administered intravenously or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses). Main Outcomes and Measures: The primary outcome was a composite of organ support-free days defined as days alive and free of respiratory and cardiovascular organ support in the intensive care unit up to day 21 and survival to hospital discharge. Values ranged from -1 organ support-free days for patients experiencing in-hospital death to 22 organ support-free days for those who survived without needing organ support. The primary analysis used a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented efficacy (improved survival, more organ support-free days, or both), an OR less than 1 represented harm, and an OR less than 1.2 represented futility. Results: Enrollment was terminated after statistical triggers for harm and futility were met. The trials had primary outcome data for 1568 critically ill patients (1037 in the vitamin C group and 531 in the control group; median age, 60 years [IQR, 50-70 years]; 35.9% were female) and 1022 patients who were not critically ill (456 in the vitamin C group and 566 in the control group; median age, 62 years [IQR, 51-72 years]; 39.6% were female). Among critically ill patients, the median number of organ support-free days was 7 (IQR, -1 to 17 days) for the vitamin C group vs 10 (IQR, -1 to 17 days) for the control group (adjusted proportional OR, 0.88 [95% credible interval {CrI}, 0.73 to 1.06]) and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility). Among patients who were not critically ill, the median number of organ support-free days was 22 (IQR, 18 to 22 days) for the vitamin C group vs 22 (IQR, 21 to 22 days) for the control group (adjusted proportional OR, 0.80 [95% CrI, 0.60 to 1.01]) and the posterior probabilities were 2.9% (efficacy), 97.1% (harm), and greater than 99.9% (futility). Among critically ill patients, survival to hospital discharge was 61.9% (642/1037) for the vitamin C group vs 64.6% (343/531) for the control group (adjusted OR, 0.92 [95% CrI, 0.73 to 1.17]) and the posterior probability was 24.0% for efficacy. Among patients who were not critically ill, survival to hospital discharge was 85.1% (388/456) for the vitamin C group vs 86.6% (490/566) for the control group (adjusted OR, 0.86 [95% CrI, 0.61 to 1.17]) and the posterior probability was 17.8% for efficacy. Conclusions and Relevance: In hospitalized patients with COVID-19, vitamin C had low probability of improving the primary composite outcome of organ support-free days and hospital survival. Trial Registration: ClinicalTrials.gov Identifiers: NCT04401150 (LOVIT-COVID) and NCT02735707 (REMAP-CAP).
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COVID-19 , Sepsis , Humanos , Femenino , Persona de Mediana Edad , Masculino , Ácido Ascórbico/uso terapéutico , Enfermedad Crítica/terapia , Enfermedad Crítica/mortalidad , Mortalidad Hospitalaria , Teorema de Bayes , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitaminas/uso terapéutico , Sepsis/tratamiento farmacológicoRESUMEN
BACKGROUND: Extubation to non-invasive ventilation (NIV) has been investigated as a strategy to wean critically ill adults from invasive ventilation and reduce ventilator-related complications. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, proceedings of four conferences and bibliographies (to June 2020) for randomised and quasi-randomised trials that compared extubation with immediate application of NIV to continued invasive weaning in intubated adults and reported mortality (primary outcome) or other outcomes. Two reviewers independently screened citations, assessed trial quality and abstracted data. RESULTS: We identified 28 trials, of moderate-to-good quality, involving 2066 patients, 44.6% with chronic obstructive pulmonary disease (COPD). Non-invasive weaning significantly reduced mortality (risk ratio (RR) 0.57, 95% CI 0.44 to 0.74; high quality), weaning failures (RR 0.59, 95% CI 0.43 to 0.81; high quality), pneumonia (RR 0.30, 95% CI 0.22 to 0.41; high quality), intensive care unit (ICU) (mean difference (MD) -4.62 days, 95% CI -5.91 to -3.34) and hospital stay (MD -6.29 days, 95% CI -8.90 to -3.68). Non-invasive weaning also significantly reduced the total duration of ventilation, duration of invasive ventilation and duration of ventilation related to weaning (MD -0.57, 95% CI -1.08 to -0.07) and tracheostomy rate. Mortality, pneumonia, reintubation and ICU stay were significantly lower in trials enrolling COPD (vs mixed) populations. CONCLUSION: Non-invasive weaning significantly reduced mortality, pneumonia and the duration of ventilation related to weaning, particularly in patients with COPD. Beneficial effects are less clear (or more careful patient selection is required) in non-COPD patients. PROSPERO REGISTRATION NUMBER: CRD42020201402.
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Ventilación no Invasiva , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Enfermedad Crítica/terapia , Humanos , Unidades de Cuidados Intensivos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Respiración Artificial , Desconexión del VentiladorRESUMEN
BACKGROUND: Among critically ill patients with acute kidney injury (AKI), earlier initiation of renal replacement therapy (RRT) may mitigate fluid accumulation and confer better outcomes among individuals with greater fluid overload at randomization. METHODS: We conducted a pre-planned post hoc analysis of the STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial. We evaluated the effect of accelerated RRT initiation on cumulative fluid balance over the course of 14 days following randomization using mixed models after censoring for death and ICU discharge. We assessed the modifying effect of baseline fluid balance on the impact of RRT initiation strategy on key clinical outcomes. Patients were categorized in quartiles of baseline fluid balance, and the effect of accelerated versus standard RRT initiation on clinical outcomes was assessed in each quartile using risk ratios (95% CI) for categorical variables and mean differences (95% CI) for continuous variables. RESULTS: Among 2927 patients in the modified intention-to-treat analysis, 2738 had available data on baseline fluid balance and 2716 (92.8%) had at least one day of fluid balance data following randomization. Over the subsequent 14 days, participants allocated to the accelerated strategy had a lower cumulative fluid balance compared to those in the standard strategy (4509 (- 728 to 11,698) versus 5646 (0 to 13,151) mL, p = 0.03). Accelerated RRT initiation did not confer greater 90-day survival in any of the baseline fluid balance quartiles (quartile 1: RR 1.11 (95% CI 0.92 to 1.34), quartile 2: RR 1.03 (0.87 to 1.21); quartile 3: RR 1.08 (95% CI 0.91 to 1.27) and quartile 4: RR 0.87 (95% CI 0.73 to 1.03), p value for trend 0.08). CONCLUSIONS: Earlier RRT initiation in critically ill patients with AKI conferred a modest attenuation of cumulative fluid balance. Nonetheless, among patients with greater fluid accumulation at randomization, accelerated RRT initiation did not have an impact on all-cause mortality. TRIAL REGISTRATION: ClinicalTrials.gov number, https://clinicaltrials.gov/ct2/show/NCT02568722 , registered October 6, 2015.
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Lesión Renal Aguda , Desequilibrio Hidroelectrolítico , Humanos , Lesión Renal Aguda/etiología , Enfermedad Crítica/terapia , Terapia de Reemplazo Renal/efectos adversos , Equilibrio HidroelectrolíticoRESUMEN
Rationale: Choosing the best ventilation strategy for acute respiratory distress syndrome (ARDS) is complex, yet it is highly relevant to clinicians during a respiratory pandemic. Objectives: To compare the effects of low Vt, high Vt, high positive end-expiratory pressure (PEEP), prone ventilation, high-frequency oscillation, and venovenous extracorporeal membrane oxygenation (VV ECMO) on mortality in ARDS. Methods: We performed a network meta-analysis of randomized trials. We applied the Grading of Recommendations Assessment, Development and Evaluation methodology to discern the relative effect of interventions on mortality. Measurements and Main Results: We analyzed 34 trials including 9,085 adults with primarily moderate-to-severe ARDS (median baseline PaO2/FiO2, 118; interquartile range, 110-143). Prone positioning combined with low Vt was the best strategy (risk ratio [RR], 0.74 [95% confidence interval (CI), 0.60-0.92] vs. low Vt; high certainty). VV ECMO was also rated among the best (RR, 0.78 [95% CI, 0.58-1.05] vs. low Vt; RR, 0.66; [95% CI, 0.49-0.88] vs. high Vt) but was rated with lower certainty because VV ECMO was restricted to very severe ARDS (mean baseline PaO2/FiO2<75). High PEEP combined with low Vt was rated intermediately (RR, 0.91 [95% CI, 0.81-1.03] vs. low Vt; low certainty; RR, 0.77 [95% CI, 0.65-0.91] vs. high Vt; moderate certainty). High Vt was rated worst (RR, 1.19 [95% CI, 1.02-1.37] vs. low Vt; moderate certainty), and we found no support for high-frequency oscillation or high Vt with prone ventilation. Conclusions: These findings suggest that combining low Vt with prone ventilation is associated with the greatest reduction in mortality for critically ill adults with moderate-to-severe ARDS.
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Respiración Artificial , Síndrome de Dificultad Respiratoria/terapia , Adulto , Humanos , Posicionamiento del Paciente , Síndrome de Dificultad Respiratoria/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND: In randomized clinical controlled trials, the choice of usual care as the comparator may be associated with better clinician uptake of the study protocol and lead to more generalizable results. However, if care processes evolve to resemble the intervention during the course of a trial, differences between the intervention group and usual care control group may narrow. We evaluated the effect on mean arterial pressure of an unblinded trial comparing a lower mean arterial pressure target to reduce vasopressor exposure, vs. a clinician-selected mean arterial pressure target, in critically ill patients at least 65 years old. METHODS: For this multicenter observational study using data collected both prospectively and retrospectively, patients were recruited from five of the seven trial sites. We compared the mean arterial pressure of patients receiving vasopressors, who met or would have met trial eligibility criteria, from two periods: [1] at least 1 month before the trial started, and [2] during the trial period and randomized to usual care, or not enrolled in the trial. RESULTS: We included 200 patients treated before and 229 after trial initiation. There were no differences in age (mean 74.5 vs. 75.2 years; p = 0.28), baseline Acute Physiology and Chronic Health Evaluation II score (median 26 vs. 26; p = 0.47) or history of chronic hypertension (n = 126 [63.0%] vs. n = 153 [66.8%]; p = 0.41). Mean of the mean arterial pressure was similar between the two periods (72.5 vs. 72.4 mmHg; p = 0.76). CONCLUSIONS: The initiation of a trial of a prescribed lower mean arterial pressure target, compared to a usual clinician-selected target, was not associated with a change in mean arterial pressure, reflecting stability in the net effect of usual clinician practices over time. Comparing prior and concurrent control groups may alleviate concerns regarding drift in usual practices over the course of a trial or permit quantification of any change.
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Presión Arterial/efectos de los fármacos , Cuidados Críticos/métodos , Vasoconstrictores/administración & dosificación , Anciano , Enfermedad Crítica , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: Compared with individual-patient randomized controlled trials, cluster randomized controlled trials have unique methodological and ethical considerations. We evaluated the rationale, methodological quality, and reporting of cluster randomized controlled trials in critical care studies. DATA SOURCES: Systematic searches of Medline, Embase, and Cochrane Central Register were performed. STUDY SELECTION: We included all cluster randomized controlled trials conducted in adult, pediatric, or neonatal critical care units from January 2005 to September 2019. DATA EXTRACTION: Two reviewers independently screened citations, reviewed full texts, protocols, and supplements of potentially eligible studies, abstracted data, and assessed methodology of included studies. DATA SYNTHESIS: From 1,902 citations, 59 cluster randomized controlled trials met criteria. Most focused on quality improvement (24, 41%), antimicrobial therapy (9, 15%), or infection control (9, 15%) interventions. Designs included parallel-group (25, 42%), crossover (21, 36%), and stepped-wedge (13, 22%). Concealment of allocation was reported in 21 studies (36%). Thirteen studies (22%) reported at least one method of blinding. The median total sample size was 1,660 patients (interquartile range, 813-4,295); the median number of clusters was 12 (interquartile range, 5-24); and the median patients per cluster was 141 (interquartile range, 54-452). Sample size calculations were reported in 90% of trials, but only 54% met Consolidated Standards of Reporting Trials guidance for sample size reporting. Twenty-seven of the studies (46%) identified a fixed number of available clusters prior to trial commencement, and only nine (15%) prespecified both the number of clusters and patients required to detect the expected effect size. Overall, 36 trials (68%) achieved the total prespecified sample size. When analyzing data, 44 studies (75%) appropriately adjusted for clustering when analyzing the primary outcome. Only 12 (20%) reported an intracluster coefficient (median 0.047 [interquartile range, 0.01-0.13]). CONCLUSIONS: Cluster randomized controlled trials in critical care typically involve a small and fixed number of relatively large clusters. The reporting of key methodological aspects of these trials is often inadequate.
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Cuidados Críticos/organización & administración , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Proyectos de Investigación , Análisis por Conglomerados , HumanosRESUMEN
OBJECTIVES: To describe the infrastructure and resources for pediatric emergency and critical care delivery in resource-limited settings worldwide. DESIGN: Cross-sectional survey with survey items developed through literature review and revised following piloting. SETTING: The electronic survey was disseminated internationally in November 2019 via e-mail directories of pediatric intensive care societies and networks and using social media. PATIENTS: Healthcare providers who self-identified as working in resource-limited settings. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Results were summarized using descriptive statistics and resource availability was compared across World Bank country income groups. We received 328 responses (238 hospitals, 60 countries), predominantly in Latin America and Sub-Saharan Africa (n = 161, 67.4%). Hospitals were in low-income (28, 11.7%), middle-income (166, 69.5%), and high-income (44, 18.4%) countries. Across 174 PICU and adult ICU admitting children, there were statistically significant differences in the proportion of hospitals reporting consistent resource availability ("often" or "always") between country income groups (p < 0·05). Resources with limited availability in lower income countries included advanced ventilatory support, invasive and noninvasive monitoring, central venous access, renal replacement therapy, advanced imaging, microbiology, biochemistry, blood products, antibiotics, parenteral nutrition, and analgesic/sedative drugs. Seventy-seven ICUs (52.7%) were staffed 24/7 by a pediatric intensivist or anesthetist. The nurse-to-patient ratio was less than 1:2 in 71 ICUs (49.7%). CONCLUSIONS: Contemporary data demonstrate significant disparity in the availability of essential and advanced human and material resources for the care of critically ill children in resource-limited settings. Minimum standards for essential pediatric emergency and critical care in resource-limited settings are needed.
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Cuidados Críticos/estadística & datos numéricos , Países en Desarrollo , Recursos en Salud/provisión & distribución , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Ventiladores Mecánicos/provisión & distribución , Niño , Estudios Transversales , Servicio de Urgencia en Hospital/estadística & datos numéricos , Capacidad de Camas en Hospitales , Humanos , Evaluación de Resultado en la Atención de Salud , PobrezaRESUMEN
OBJECTIVES: To determine whether the "Checklist for Early Recognition and Treatment of Acute Illness and Injury" decision support tool during ICU admission and rounding is associated with improvements in nonadherence to evidence-based daily care processes and outcomes in variably resourced ICUs. DESIGN, SETTINGS, PATIENTS: This before-after study was performed in 34 ICUs (15 countries) from 2013 to 2017. Data were collected for 3 months before and 6 months after Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation. INTERVENTIONS: Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation using remote simulation training. MEASUREMENTS AND MAIN RESULTS: The coprimary outcomes, modified from the original protocol before data analysis, were nonadherence to 10 basic care processes and ICU and hospital length of stay. There were 1,447 patients in the preimplementation phase and 2,809 patients in the postimplementation phase. After adjusting for center effect, Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation was associated with reduced nonadherence to care processes (adjusted incidence rate ratio [95% CI]): deep vein thrombosis prophylaxis (0.74 [0.68-0.81), peptic ulcer prophylaxis (0.46 [0.38-0.57]), spontaneous breathing trial (0.81 [0.76-0.86]), family conferences (0.86 [0.81-0.92]), and daily assessment for the need of central venous catheters (0.85 [0.81-0.90]), urinary catheters (0.84 [0.80-0.88]), antimicrobials (0.66 [0.62-0.71]), and sedation (0.62 [0.57-0.67]). Analyses adjusted for baseline characteristics showed associations of Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation with decreased ICU length of stay (adjusted ratio of geometric means [95% CI]) 0.86 [0.80-0.92]), hospital length of stay (0.92 [0.85-0.97]), and hospital mortality (adjusted odds ratio [95% CI], 0.81 (0.69-0.95). CONCLUSIONS: A quality-improvement intervention with remote simulation training to implement a decision support tool was associated with decreased nonadherence to daily care processes, shorter length of stay, and decreased mortality.
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Enfermedad Aguda/epidemiología , Lista de Verificación , Producto Interno Bruto/estadística & datos numéricos , Unidades de Cuidados Intensivos/organización & administración , Mejoramiento de la Calidad/organización & administración , Heridas y Lesiones/epidemiología , Anciano , Reglas de Decisión Clínica , Femenino , Adhesión a Directriz , Humanos , Cuidados para Prolongación de la Vida/métodos , Masculino , Persona de Mediana Edad , Péptidos Cíclicos , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Indicadores de Calidad de la Atención de Salud , Índice de Severidad de la Enfermedad , Entrenamiento Simulado , Factores SocioeconómicosRESUMEN
Available animal and cell line models have suggested that specific therapeutics might be effective in treating Middle East respiratory syndrome (MERS). We conducted a systematic review of evidence for treatment with pharmacologic and supportive therapies. We developed a protocol and searched 5 databases for studies describing treatment of MERS and deaths in MERS patients. Risk of bias (RoB) was assessed by using ROBINS-I tool. We retrieved 3,660 unique citations; 20 observational studies met eligibility, and we studied 13 therapies. Most studies were at serious or critical RoB; no studies were at low RoB. One study, at moderate RoB, showed reduced mortality rates in severe MERS patients with extracorporeal membrane oxygenation; no other studies showed a significant lifesaving benefit to any treatment. The existing literature on treatments for MERS is observational and at moderate to critical RoB. Clinical trials are needed to guide treatment decisions.
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Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Coronavirus del Síndrome Respiratorio de Oriente Medio , Infecciones por Coronavirus/virología , HumanosRESUMEN
OBJECTIVE: To describe the performance of prognostic models for mortality or clinical deterioration events among hospitalized children developed or validated in low- and middle-income countries. STUDY DESIGN: A medical librarian systematically searched EMBASE, Ovid Medline, Scopus, Cochrane Library, EBSCO Global Health, LILACS, African Index Medicus, African Journals Online, African Healthline, Med-Carib, and Global Index Medicus (from 2000 to October 2019). We included citations that described the development or validation of a pediatric prognostic model for hospital mortality or clinical deterioration events in low- and middle-income countries. In duplicate and independently, we extracted data on included populations and model prognostic performance and evaluated risk of bias using the Prediction model Risk Of Bias Assessment Tool. RESULTS: Of 41 279 unique citations, we included 15 studies describing 15 prognostic models for mortality and 3 models for clinical deterioration events. Six models were validated in >1 external cohort. The Lambarene Organ Dysfunction Score (0.85 [0.77-0.92]) and Signs of Inflammation in Children that Kill (0.85 [0.82-0.88]) had the highest summary C-statistics (95% CI) for discrimination. Calibration and classification measures were poorly reported. All models were at high risk of bias owing to inappropriate selection of predictor variables and handling of missing data and incomplete performance measure reporting. CONCLUSIONS: Several prognostic models for mortality and clinical deterioration events have been validated in single cohorts, with good discrimination. Rigorous validation that conforms to current standards for prediction model studies and updating of existing models are needed before clinical implementation.
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Deterioro Clínico , Puntuación de Alerta Temprana , Mortalidad Hospitalaria , Puntuaciones en la Disfunción de Órganos , Adolescente , Niño , Preescolar , Países en Desarrollo , Humanos , Lactante , Recién Nacido , Medición de Riesgo/métodos , Estudios de Validación como AsuntoRESUMEN
BACKGROUND: Predicting neurological outcome in comatose survivors of cardiac arrest relies on clinical findings, radiological and neurophysiological test results. To evaluate the predictive accuracy of brain computed tomography (CT) and magnetic resonance imaging (MRI) for prognostication of neurological outcomes after cardiac arrest. METHODS: We searched MEDLINE (database inception to August 2018) and included all observational cohort studies or randomized controlled trials including adult (16 years or older) survivors of cardiac arrest which evaluated the diagnostic accuracy of CT or MRI for predicting neurologic outcome or mortality. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All review stages were conducted independently by 2 reviewers, and where possible data were pooled using bivariate meta-analysis. The main outcome was to evaluate the of accuracy of CT and MRI in neuroprognostication of patients after cardiac arrest. RESULTS: We included 44 studies that examined brain CT (n = 24) or MRI (n = 21) in 4008 (n per study, 9-398) patients. Decreased grey to white matter ratio on CT (20 studies) was useful for predicting poor neurological outcome (sensitivity 0.44, 95% CI 0.29-0.60; specificity 0.97, 95% CI 0.93-0.99; positive likelihood ratio [LR+] 13.8, 95% CI 6.9-27.7). Similarly, diffusion-weighted imaging (DWI) on MRI (16 studies; sensitivity 0.77, 95% CI 0.65-0.85; specificity 0.92, 95% CI 0.85-0.96; LR+ 9.2, 95% CI 5.2-16.4) and DWI and fluid-attenuated inversion recovery (FLAIR) MRI (4 studies, sensitivity 0.70, 95% CI 0.43-0.88; specificity 0.95, 95% CI 0.79-0.99; LR+ 13.4, 95% CI 3.5-51.2) were useful for predicting poor neurological outcomes. We found marked heterogeneity in timing of radiological examinations and neurological assessments relative to the cardiac arrest. CONCLUSION: Decreased grey to white matter ratio on CT and DWI or DWI and FLAIR on MRI are useful adjuncts for predicting poor early neurological outcome after cardiac arrest.