Twenty percent human albumin solution fluid bolus administration therapy in patients after cardiac surgery-II: a multicentre randomised controlled trial.

PURPOSE: After cardiac surgery, fluid bolus therapy (FBT) with 20% human albumin may facilitate less fluid and vasopressor administration than FBT with crystalloids. We aimed to determine whether, after cardiac surgery, FBT with 20% albumin reduces the duration of vasopressor therapy compared with crystalloid FBT. METHODS: We conducted a multicentre, parallel-group, open-label, randomised clinical trial in six intensive care units (ICUs) involving cardiac surgery patients deemed to require FBT. We randomised 240 patients to receive up to 400 mL of 20% albumin/day as FBT, followed by 4% albumin for any subsequent FBT on that day, or to crystalloid FBT for at least the first 1000 mL, with use of crystalloid or 4% albumin FBT thereafter. The primary outcome was the cumulative duration of vasopressor therapy. Secondary outcomes included fluid balance. RESULTS: Of 480 randomised patients, 466 provided consent and contributed to the primary outcome (mean age 65 years; median EuroSCORE II 1.4). The cumulative median duration of vasopressor therapy was 7 (interquartile range [IQR] 0-19.6) hours with 20% albumin and 10.8 (IQR 0-22.8) hours with crystalloids (difference - 3.8 h, 95% confidence interval [CI] - 8 to 0.4; P = 0.08). Day one fluid balance was less with 20% albumin FBT (mean difference - 701 mL, 95% CI - 872 to - 530). CONCLUSIONS: In patients after cardiac surgery, when compared to a crystalloid-based FBT, 20% albumin FBT was associated with a reduced positive fluid balance but did not significantly reduce the duration of vasopressor therapy.

The interaction of net ultrafiltration rate with urine output and fluid balance after continuous renal replacement therapy initiation: A multi-Centre study.

PURPOSE: During continuous renal replacement therapy (CRRT), a high net ultrafiltration rate (NUF) may worsen the decrease in urine output (UO) associated with starting CRRT. However, fluid balance (FB) may modulate this association. We aimed to examine the relationship between NUF, UO and FB at the start of CRRT. METHODS: A retrospective cohort study of 1030 CRRT-treated patients admitted to two tertiary ICUs. RESULTS: Median age was 60 years (IQR, 48-70), median APACHE III was 94 (IQR, 76-114) and median NUF rate was 0.7 mL/kg/h. In the 24 h after CRRT started, the mean hourly UO decreased from 25.5 mL to 11.9 mL (P < 0.001). Moreover, after adjusting for multiple confounders on multivariable analysis, a higher NUF was not significantly associated with a lower UO (-1.5 mL/kg for every 1 mL/kg/h increase in NUF; 95% CI -3.1 to 0.04; p = 0.064). In addition, pre-CRRT FB did not modulate the above relationship between higher NUF and lower UO. CONCLUSION: A higher NUF rate was not significantly associated with a greater immediate and sustained reduction in UO after CRRT commencement. FB before CRRT was also not associated with a greater reduction in UO. These findings do not provide evidence for an effect of NUF on renal function.

How a positive fluid balance develops in acute kidney injury: A binational, observational study.

PURPOSE: A positive fluid balance (FB) is associated with harm in intensive care unit (ICU) patients with acute kidney injury (AKI). We aimed to understand how a positive balance develops in such patients. METHODS: Multinational, retrospective cohort study of critically ill patients with AKI not requiring renal replacement therapy. RESULTS: AKI occurred at a median of two days after admission in 7894 (17.3%) patients. Cumulative FB became progressively positive, peaking on day three despite only 848 (10.7%) patients receiving fluid resuscitation in the ICU. In those three days, persistent crystalloid use (median:60.0 mL/h; IQR 28.9-89.2), nutritional intake (median:18.2 mL/h; IQR 0.0-45.9) and limited urine output (UO) (median:70.8 mL/h; IQR 49.0-96.7) contributed to a positive FB. Although UO increased each day, it failed to match input, with only 797 (10.1%) patients receiving diuretics in ICU. After adjustment, a positive FB four days after AKI diagnosis was associated with an increased risk of hospital mortality (OR 1.12;95% confidence intervals 1.05-1.19;p-value <0.001). CONCLUSION: Among ICU patients with AKI, cumulative FB increased after diagnosis and was associated with an increased risk of mortality. Continued crystalloid administration, increased nutritional intake, limited UO, and minimal use of diuretics all contributed to positive FB. KEY POINTS: Question How does a positive fluid balance develop in critically ill patients with acute kidney injury? Findings Cumulative FB increased after AKI diagnosis and was secondary to persistent crystalloid fluid administration, increasing nutritional fluid intake, and insufficient urine output. Despite the absence of resuscitation fluid and an increasing cumulative FB, there was persistently low diuretics use, ongoing crystalloid use, and a progressive escalation of nutritional fluid therapy. Meaning Current management results in fluid accumulation after diagnosis of AKI, as a result of ongoing crystalloid administration, increasing nutritional fluid, limited urine output and minimal diuretic use.

Alternative approaches to analyzing ventilator-free days, mortality and duration of ventilation in critical care research / Abordagens alternativas para analisar dias livres de ventilador, mortalidade e duração da ventilação em estudos de cuidados intensivos

ABSTRACT Objective: To discuss the strengths and limitations of ventilator-free days and to provide a comprehensive discussion of the different analytic methods for analyzing and interpreting this outcome. Methods: Using simulations, the power of different analytical methods was assessed, namely: quantile (median) regression, cumulative logistic regression, generalized pairwise comparison, conditional approach and truncated approach. Overall, 3,000 simulations of a two-arm trial with n = 300 per arm were computed using a two-sided alternative hypothesis and a type I error rate of α = 0.05. Results: When considering power, median regression did not perform well in studies where the treatment effect was mainly driven by mortality. Median regression performed better in situations with a weak effect on mortality but a strong effect on duration, duration only, and moderate mortality and duration. Cumulative logistic regression was found to produce similar power to the Wilcoxon rank-sum test across all scenarios, being the best strategy for the scenarios of moderate mortality and duration, weak mortality and strong duration, and duration only. Conclusion: In this study, we describe the relative power of new methods for analyzing ventilator-free days in critical care research. Our data provide validation and guidance for the use of the cumulative logistic model, median regression, generalized pairwise comparisons, and the conditional and truncated approach in specific scenarios.

RESUMO Objetivo: Discutir os pontos fortes e as limitações dos dias livres de ventilador e fornecer uma discussão abrangente dos diferentes métodos analíticos para analisar e interpretar esse desfecho. Métodos: Por meio de simulações, avaliou-se o poder de diferentes métodos analíticos, a saber: regressão quantílica (mediana), regressão logística cumulativa, comparação generalizada entre pares, abordagem condicional e abordagem truncada. No total, foram computadas 3.000 simulações de um estudo de dois braços com n = 300 por braço, usando uma hipótese alternativa bilateral e uma taxa de erro tipo I de α = 0,05. Resultados: Ao considerar o poder, a regressão mediana não teve bom desempenho em estudos em que o efeito do tratamento foi impulsionado principalmente pela mortalidade. A regressão mediana teve desempenho melhor em situações com efeito fraco na mortalidade, mas forte na duração, somente na duração e na mortalidade e duração moderadas. Verificou-se que a regressão logística cumulativa produziu um poder semelhante ao do teste de soma de postos de Wilcoxon em todos os cenários, sendo a melhor estratégia nos cenários de mortalidade e duração moderadas, mortalidade fraca e duração forte, e apenas duração. Conclusão: Neste estudo, descrevemos o poder relativo de novos métodos para analisar os dias livres de ventilador em estudos de cuidados intensivos. Nossos dados fornecem validação e orientação quanto ao uso do modelo logístico cumulativo, regressão mediana, comparações generalizadas entre pares e a abordagem condicional e truncada em cenários específicos.

Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study / Dapagliflozina em pacientes com doença crítica: justificativa e desenho do estudo DEFENDER

ABSTRACT Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. Methods: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. Conclusion: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. ClinicalTrials.gov registry: NCT05558098

RESUMO Antecedentes: A doença crítica é um importante ônus permanente da assistência médica em todo o mundo e está associada a altas taxas de mortalidade. Os inibidores do cotransportador de sódio-glicose do tipo 2 têm demonstrado consistentemente benefícios nos desfechos cardiovasculares e renais. Os efeitos dos inibidores do cotransportador de sódio-glicose do tipo 2 em doenças agudas ainda não foram devidamente investigados. Métodos: O DEFENDER é um estudo de iniciativa do investigador, multicêntrico, randomizado, aberto, desenhado para avaliar a eficácia e a segurança da dapagliflozina em 500 participantes adultos com disfunção orgânica aguda hospitalizados na unidade de terapia intensiva. Os participantes aptos serão randomizados 1:1 para receber 10mg de dapagliflozina e o tratamento padrão por até 14 dias ou apenas o tratamento padrão. O desfecho primário é um composto hierárquico de mortalidade hospitalar, início de terapia renal substitutiva e tempo de internação na unidade de terapia intensiva, até 28 dias. O monitoramento da segurança será rigoroso durante todo o estudo. Conclusão: O DEFENDER é o primeiro estudo desenvolvido para investigar o uso de um inibidor do cotransportador de sódio-glicose do tipo 2 em pacientes de unidade de terapia intensiva geral com disfunção orgânica aguda. O estudo fornecerá informações relevantes sobre o uso de medicamentos dessa classe promissora em pacientes críticos. Registro ClincalTrials.gov: NCT05558098

Closed-Loop ventilation using sidestream versus mainstream capnography for automated adjustments of minute ventilation-A randomized clinical trial in cardiac surgery patients.

BACKGROUND: INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop ventilation mode that uses capnography to adjust tidal volume (VT) and respiratory rate according to a user-set end-tidal CO2 (etCO2) target range. We compared sidestream versus mainstream capnography with this ventilation mode with respect to the quality of breathing in patients after cardiac surgery. METHODS: Single-center, single-blinded, non-inferiority, randomized clinical trial in adult patients scheduled for elective cardiac surgery that were expected to receive at least two hours of postoperative ventilation in the ICU. Patients were randomized 1:1 to closed-loop ventilation with sidestream or mainstream capnography. Each breath was classified into a zone based on the measured VT, maximum airway pressure, etCO2 and pulse oximetry. The primary outcome was the proportion of breaths spent in a predefined 'optimal' zone of ventilation during the first three hours of postoperative ventilation, with a non-inferiority margin for the difference in the proportions set at -20%. Secondary endpoints included the proportion of breaths in predefined 'acceptable' and 'critical' zones of ventilation, and the proportion of breaths with hypoxemia. RESULTS: Of 80 randomized subjects, 78 were included in the intention-to-treat analysis. We could not confirm the non-inferiority of closed-loop ventilation using sidestream with respect to the proportion of breaths in the 'optimal' zone (mean ratio 0.87 [0.77 to ∞]; P = 0.116 for non-inferiority). The proportion of breaths with hypoxemia was higher in the sidestream capnography group versus the mainstream capnography group. CONCLUSIONS: We could not confirm that INTELLiVENT-ASV using sidestream capnography is non-inferior to INTELLiVENT-ASV using mainstream capnography with respect to the quality of breathing in subjects receiving postoperative ventilation after cardiac surgery. TRIAL REGISTRATION: NCT04599491 (clinicaltrials.gov).

Attributable mortality due to nosocomial sepsis in Brazilian hospitals: a case-control study.

BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.

A PILOT STUDY OF ANGIOTENSIN II AS PRIMARY VASOPRESSOR IN CRITICALLY ILL ADULTS WITH VASODILATORY HYPOTENSION: THE ARAMIS STUDY.

ABSTRACT: Objective: The aim of the study is to evaluate the efficacy and safety of using angiotensin II (Ang2) as primary vasopressor for vasodilatory hypotension. Methods: This was a prospective observational study of critically ill adults admitted to an academic intensive care unit (ICU) with vasodilatory hypotension. We treated 40 patients with Ang2 as primary vasopressor and compared them with 80 matched controls who received conventional vasopressors (norepinephrine, vasopressin, metaraminol, epinephrine, or combinations). Results : Mean age was 63 years and median Acute Physiology and Chronic Health Evaluation III score was 65. Ang2 patients had lower ICU mortality (10% vs 26%, P = 0.04); however, their 28- and 90-day mortality was not significantly different (18% vs 29%, P = 0.18; 22% vs 30%, P = 0.39). Peak serum creatinine levels were similar (128 vs 126 µmol/L, P = 0.81), as was the incidence and stage of acute kidney injury (70% vs 74%, P = 0.66), requirement for continuous renal replacement therapy (14% vs 13%, P = 0.84), and risk of major adverse kidney events at 7 days (20% vs 29%, P = 0.30). However, Ang2 patients with prior exposure to renin angiotensin aldosterone system inhibitors had a lower peak serum creatinine ( P = 0.03 for interaction) than conventional vasopressors patients, and serum troponin elevations were less common with Ang2 (8% vs 22%, P = 0.04). The incidence of thromboembolic complications was similar. Conclusions: Primary Ang2 administration in vasodilatory hypotension did not seem harmful compared with conventional vasopressors. Although Ang2 did not decrease peak serum creatinine levels or major adverse kidney events, its effects on intensive care unit survival, serum troponin, and renal function in patients on renin angiotensin aldosterone system inhibitors warrant further exploration in randomized trials (ACTRN12621000281897).

Evaluation of ferritin and the ferritin index as prognostic biomarkers in septic shock.

BACKGROUND: Ferritin, an acute phase reactant, and the ferritin index (FI = observed ferritin level/upper limit of normal level for age and sex) may be prognostic biomarkers in septic shock and cardiac surgery patients. OBJECTIVE: The purpose of this exploratory study is to assess the outcome associations of ferritin and FI levels in septic shock compared to post-cardiac surgery patients. DESIGN: This was a prospective, double-centre, observational study. SETTING: The study setting involved two adult intensive care units (ICUs) in Victoria, Australia. PARTICIPANTS: Sixty-one septic shock and 30 post-cardiac surgery patients participated in this study. MAIN OUTCOME MEASURES: We measured ferritin and FI on ICU admission (T1) and 24 h later (T2) to assess its correlation with mortality, illness severity, and hospital length of stay (LOS). RESULTS: The baseline characteristics of patients in the septic shock group and cardiac surgery group were similar apart from illness severity scores (APACHE III and modified SOFA score). Septic shock patients had more physiological derangements as well as greater use and higher doses of norepinephrine at both T1 and T2. Septic shock patients had significantly higher median ferritin levels (372 µg/L versus 198 µg/L; p < 0.001 at T1, 457 µg/L versus 264 µg/L; p = 0.001 at T2) than post-cardiac surgery patients. Ferritin levels, however, did not have a linear correlation with illness severity or hospital mortality. Instead, there was an association between high ferritin levels at T2 and longer ICU (p = 0.017) and hospital LOS (p = 0.013). Females with septic shock had significantly higher FI (p < 0.001 at T1, p = 0.004 at T2) than males. CONCLUSION: In septic shock patients, ferritin levels and FI were twice the level compared to post-cardiac surgery patients. Both had no association with mortality, but levels above the median at 24 h were associated with longer ICU and hospital LOS.

Safety and Feasibility of Intraoperative High PEEP Titrated to the Lowest Driving Pressure (ΔP)-Interim Analysis of DESIGNATION.

Uncertainty remains about the best level of intraoperative positive end-expiratory pressure (PEEP). An ongoing RCT ('DESIGNATION') compares an 'individualized high PEEP' strategy ('iPEEP')-titrated to the lowest driving pressure (ΔP) with recruitment maneuvers (RM), with a 'standard low PEEP' strategy ('low PEEP')-using 5 cm H2O without RMs with respect to the incidence of postoperative pulmonary complications. This report is an interim analysis of safety and feasibility. From September 2018 to July 2022, we enrolled 743 patients. Data of 698 patients were available for this analysis. Hypotension occurred more often in 'iPEEP' vs. 'low PEEP' (54.7 vs. 44.1%; RR, 1.24 (95% CI 1.07 to 1.44); p < 0.01). Investigators were compliant with the study protocol 285/344 patients (82.8%) in 'iPEEP', and 345/354 patients (97.5%) in 'low PEEP' (p < 0.01). Most frequent protocol violation was missing the final RM at the end of anesthesia before extubation; PEEP titration was performed in 99.4 vs. 0%; PEEP was set correctly in 89.8 vs. 98.9%. Compared to 'low PEEP', the 'iPEEP' group was ventilated with higher PEEP (10.0 (8.0-12.0) vs. 5.0 (5.0-5.0) cm H2O; p < 0.01). Thus, in patients undergoing general anesthesia for open abdominal surgery, an individualized high PEEP ventilation strategy is associated with hypotension. The protocol is feasible and results in clear contrast in PEEP. DESIGNATION is expected to finish in late 2023.

Efeitos da solução balanceada em desfechos de curto prazo em pacientes com traumatismo craniencefálico: uma análise secundária do ensaio clínico randomizado BaSICS / Effects of balanced solution on short-term outcomes in traumatic brain injury patients: a secondary analysis of the BaSICS randomized trial

RESUMO Objetivo: Descrever os efeitos do uso de soluções balanceadas nos desfechos de curto prazo de pacientes com traumatismo craniencefálico incluídos no estudo BaSICS. Métodos: Os pacientes foram randomizados para receber solução salina 0,9% ou solução balanceada durante a internação em unidade de terapia intensiva. O desfecho primário foi mortalidade em 90 dias, já os desfechos secundários foram dias de vida e sem internação em unidade de terapia intensiva aos 28 dias. O desfecho primário foi avaliado por regressão logística bayesiana. O desfecho secundário foi avaliado usando regressão beta-binomial inflada de zeros bayesiana. Resultados: Incluímos 483 pacientes (236 no braço de solução salina 0,9% e 247 no braço de solução balanceada). Foram incluídos 338 pacientes (70%) com pontuação na escala de coma de Glasgow ≤ 12. A probabilidade geral de que soluções balanceadas estivessem associadas a maior mortalidade em 90 dias foi de 0,98 (RC de 1,48; ICr95% 1,04 - 2,09). Esse aumento de mortalidade foi particularmente perceptível em pacientes com pontuação na escala de coma de Glasgow abaixo de 6 no momento da inclusão (probabilidade de dano de 0,99). Soluções balanceadas foram associadas a -1,64 dia de vida e sem internação em unidade de terapia intensiva aos 28 dias (ICr95% -3,32 - 0,00) com probabilidade de dano de 0,97. Conclusão: Houve alta probabilidade de que soluções balanceadas estivessem associadas a alta mortalidade em 90 dias, menos dias de vida e sem internação em unidade de terapia intensiva aos 28 dias. ClinicalTrials.gov:NCT02875873

ABSTRACT Objective: To describe the effects of balanced solution use on the short-term outcomes of patients with traumatic brain injury enrolled in BaSICS trial. Methods: Patients were randomized to receive either 0.9% saline or balanced solution during their intensive care unit stay. The primary endpoint was 90-day mortality, and the secondary outcomes were days alive and free of intensive care unit stay at 28 days. The primary endpoint was assessed using Bayesian logistic regression. The secondary endpoint was assessed using a Bayesian zero-inflated beta binomial regression. Results: We included 483 patients (236 in the 0.9% saline arm and 247 in the balanced solution arm). A total of 338 patients (70%) with a Glasgow coma scale score ≤ 12 were enrolled. The overall probability that balanced solutions were associated with higher 90-day mortality was 0.98 (OR 1.48; 95%CrI 1.04 - 2.09); this mortality increment was particularly noticeable in patients with a Glasgow coma scale score below 6 at enrollment (probability of harm of 0.99). Balanced solutions were associated with -1.64 days alive and free of intensive care unit at 28 days (95%CrI -3.32 - 0.00) with a probability of harm of 0.97. Conclusion: There was a high probability that balanced solutions were associated with high 90-day mortality and fewer days alive and free of intensive care units at 28 days. ClinicalTrials.gov:NCT02875873

Associations of dynamic driving pressure and mechanical power with postoperative pulmonary complications-posthoc analysis of two randomised clinical trials in open abdominal surgery.

Background: While an association of the intraoperative driving pressure with postoperative pulmonary complications has been described before, it is uncertain whether the intraoperative mechanical power is associated with postoperative pulmonary complications. Methods: Posthoc analysis of two international, multicentre randomised clinical trials (ISRCTN70332574 and NCT02148692) conducted between 2011-2013 and 2014-2018, in patients undergoing open abdominal surgery comparing the effect of two different positive end-expiratory pressure (PEEP) levels on postoperative pulmonary complications. Time-weighted average dynamic driving pressure and mechanical power were calculated for individual patients. A multivariable logistic regression model adjusted for confounders was used to assess the independent associations of driving pressure and mechanical power with the occurrence of a composite of postoperative pulmonary complications, the primary endpoint of this posthoc analysis. Findings: In 1191 patients included, postoperative pulmonary complications occurrence was 35.9%. Median time-weighted average driving pressure and mechanical power were 14·0 [11·0-17·0] cmH2O, and 7·6 [5·1-10·0] J/min, respectively. While driving pressure was not independently associated with postoperative pulmonary complications (odds ratio, 1·06 [95% CI 0·88-1·28]; p=0.534), the mechanical power had an independent association with the occurrence of postoperative pulmonary complications (odds ratio, 1·28 [95% CI 1·05-1·57]; p=0.016). These findings were independent of body mass index or the level of PEEP used, i.e., independent of the randomisation arm. Interpretation: In this merged cohort of surgery patients, higher intraoperative mechanical power was independently associated with postoperative pulmonary complications. Mechanical power could serve as a summary ventilatory biomarker for the risk for postoperative pulmonary complications in these patients, but our findings need confirmation in other, preferably prospective studies. Funding: The two original studies were supported by unrestricted grants from the European Society of Anaesthesiology and the Amsterdam University Medical Centers, Location AMC. For this current analysis, no additional funding was requested. The funding sources had neither a role in the design, collection of data, statistical analysis, interpretation of data, writing of the report, nor in the decision to submit the paper for publication.

Plano de análise estatística de um ensaio clínico randomizado em cluster em unidades de terapia intensiva geral adulto no Brasil: TELE-critical care verSus usual Care On ICU PErformance (TELESCOPE) / Statistical analysis of a cluster-randomized clinical trial on adult general intensive care units in Brazil: TELE-critical care verSus usual Care On ICU PErformance (TELESCOPE) trial

RESUMO Objetivo: O ensaio TELE-critical Care verSus usual Care On ICU PErformance (TELESCOPE) visa avaliar se uma intervenção complexa por telemedicina em unidades de terapia intensiva, que se concentra em rondas multidisciplinares diárias realizadas por intensivistas a distância, reduzirá o tempo de permanência na unidade de terapia intensiva em comparação com os cuidados habituais. Métodos: O TELESCOPE é um ensaio nacional, multicêntrico, controlado, aberto, randomizado em cluster. O estudo testa a eficácia de rondas multidisciplinares diárias realizadas por um intensivista por meio de telemedicina em unidades de terapia intensiva brasileiras. O protocolo foi aprovado pelo Comitê de Ética em Pesquisa local do centro coordenador do estudo e pelo Comitê de Ética em Pesquisa local de cada uma das 30 unidades de terapia intensiva, de acordo com a legislação brasileira. O ensaio está registado no ClinicalTrials.gov (NCT03920501). O desfecho primário é o tempo de internação na unidade de terapia intensiva, que será analisado considerando o período basal e a estrutura dos dados em cluster, sendo ajustado por covariáveis predefinidas. Os desfechos exploratórios secundários incluem a classificação de desempenho da unidade de terapia intensiva, a mortalidade hospitalar, a incidência de infecções nosocomiais, o número de dias sem ventilação mecânica aos 28 dias, a taxa de pacientes que recebem alimentação oral ou enteral, a taxa de pacientes sob sedação leve ou em alerta e calmos e a taxa de pacientes sob normoxemia. Conclusão: De acordo com as melhores práticas do ensaio, divulgamos nossa análise estatística antes de bloquear a base de dados e iniciar as análises. Esperamos que essa prática de notificação evite o viés das análises e aprimore a interpretação dos resultados apresentados. Registro no ClinicalTrials.gov:NCT03920501

ABSTRACT Objective: The TELE-critical Care verSus usual Care On ICU PErformance (TELESCOPE) trial aims to assess whether a complex telemedicine intervention in intensive care units, which focuses on daily multidisciplinary rounds performed by remote intensivists, will reduce intensive care unit length of stay compared to usual care. Methods: The TELESCOPE trial is a national, multicenter, controlled, open label, cluster randomized trial. The study tests the effectiveness of daily multidisciplinary rounds conducted by an intensivist through telemedicine in Brazilian intensive care units. The protocol was approved by the local Research Ethics Committee of the coordinating study center and by the local Research Ethics Committee from each of the 30 intensive care units, following Brazilian legislation. The trial is registered with ClinicalTrials. gov (NCT03920501). The primary outcome is intensive care unit length of stay, which will be analyzed accounting for the baseline period and cluster structure of the data and adjusted by prespecified covariates. Secondary exploratory outcomes included intensive care unit performance classification, in-hospital mortality, incidence of nosocomial infections, ventilator-free days at 28 days, rate of patients receiving oral or enteral feeding, rate of patients under light sedation or alert and calm, and rate of patients under normoxemia. Conclusion: According to the trial's best practice, we report our statistical analysis prior to locking the database and beginning analyses. We anticipate that this reporting practice will prevent analysis bias and improve the interpretation of the reported results. ClinicalTrials.gov registration:NCT03920501

Effect of intraoperative PEEP with recruitment maneuvers on the occurrence of postoperative pulmonary complications during general anesthesia--protocol for Bayesian analysis of three randomized clinical trials of intraoperative ventilation.

Background: Using the frequentist approach, a recent meta-analysis of three randomized clinical trials in patients undergoing intraoperative ventilation during general anesthesia for major surgery failed to show the benefit of ventilation that uses high positive end-expiratory pressure with recruitment maneuvers when compared to ventilation that uses low positive end-expiratory pressure without recruitment maneuvers. Methods: We designed a protocol for a Bayesian analysis using the pooled dataset. The multilevel Bayesian logistic model will use the individual patient data. Prior distributions will be prespecified to represent a varying level of skepticism for the effect estimate. The primary endpoint will be a composite of postoperative pulmonary complications (PPC) within the first seven postoperative days, which reflects the primary endpoint of the original studies. We preset a range of practical equivalence to assess the futility of the intervention with an interval of odds ratio (OR) between 0.9 and 1.1 and assess how much of the 95% of highest density interval (HDI) falls between the region of practical equivalence. Ethics and dissemination: The used data derive from approved studies that were published in recent years. The findings of this current analysis will be reported in a new manuscript, drafted by the writing committee on behalf of the three research groups. All investigators listed in the original trials will serve as collaborative authors.

Intraoperative open lung condition and postoperative pulmonary complications. A secondary analysis of iPROVE and iPROVE-O2 trials.

BACKGROUND: The preventive role of an intraoperative recruitment maneuver plus open lung approach (RM + OLA) ventilation on postoperative pulmonary complications (PPC) remains unclear. We aimed at investigating whether an intraoperative open lung condition reduces the risk of developing a composite of PPCs. METHODS: Post hoc analysis of two randomized controlled trials including patients undergoing abdominal surgery. Patients were classified according to the intraoperative lung condition as "open" (OL) or "non-open" (NOL) if PaO2 /FIO2 ratio was ≥ or <400 mmHg, respectively. We used a multivariable logistic regression model that included potential confounders selected with directed acyclic graphs (DAG) using Dagitty software built with variables that were considered clinically relevant based on biological mechanism or evidence from previously published data. PPCs included severe acute respiratory failure, acute respiratory distress syndrome, and pneumonia. RESULTS: A total of 1480 patients were included in the final analysis, with 718 (49%) classified as OL. The rate of severe PPCs during the first seven postoperative days was 6.0% (7.9% in the NOL and 4.4% in the OL group, p = .007). OL was independently associated with a lower risk for severe PPCs during the first 7 and 30 postoperative days [odds ratio of 0.58 (95% CI 0.34-0.99, p = .04) and 0.56 (95% CI 0.34-0.94, p = .03), respectively]. CONCLUSIONS: An intraoperative open lung condition was associated with a reduced risk of developing severe PPCs in intermediate-to-high risk patients undergoing abdominal surgery. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT02158923 (iPROVE), NCT02776046 (iPROVE-O2).

Associations Between Expiratory Flow Limitation and Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery.

OBJECTIVES: To determine whether driving pressure and expiratory flow limitation are associated with the development of postoperative pulmonary complications (PPCs) in cardiac surgery patients. DESIGN: Prospective cohort study. SETTING: University Hospital San Raffaele, Milan, Italy. PARTICIPANTS: Patients undergoing elective cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the occurrence of a predefined composite of PPCs. The authors determined the association among PPCs and intraoperative ventilation parameters, mechanical power and energy load, and occurrence of expiratory flow limitation (EFL) assessed with the positive end-expiratory pressure test. Two hundred patients were enrolled, of whom 78 (39%) developed one or more PPCs. Patients with PPCs, compared with those without PPCs, had similar driving pressure (mean difference [MD] -0.1 [95% confidence interval (CI), -1.0 to 0.7] cmH2O, p = 0.561), mechanical power (MD 0.5 [95% CI, -0.3 to 1.1] J/m, p = 0.364), and total energy load (MD 95 [95% CI, -78 to 263] J, p = 0.293), but they had a higher incidence of EFL (51% v 38%, p = 0.005). Only EFL was associated independently with the development of PPCs (odds ratio 2.46 [95% CI, 1.28-4.80], p = 0.007). CONCLUSIONS: PPCs occurred frequently in this patient population undergoing cardiac surgery. PPCs were associated independently with the presence of EFL but not with driving pressure, total energy load, or mechanical power.

Hydroxychloroquine for treatment of COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT Objective We performed a systematic review of the literature and meta-analysis on the efficacy and safety of hydroxychloroquine to treat COVID-19 patients. Methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS (January 2019 to March 2021) for patients aged 18 years or older, who had COVID-19 and were treated with hydroxychloroquine versus placebo or standard of care. We also searched the WHO Clinical Trials Registry for ongoing and recently completed studies, and the reference lists of selected articles and reviews for possible relevant studies, with no restrictions regarding language or publication status. Random-effects models were used to obtain pooled mean differences of treatment effect on mortality, and serious adverse effects between hydroxychloroquine and the Control Group (standard of care or placebo); heterogeneity was assessed using the I2 and the Cochran´s Q statistic. Results Nine studies met the inclusion criteria and were included in the meta-analysis. There was no significant difference in mortality rate between patients treated with hydroxychloroquine compared to standard of care or placebo (16.7% versus 18.5%; pooled risk ratio 1.09; 95% confidence interval: 0.99-1.19). Also, the rate of serious adverse effects was similar between both Groups, Hydroxychloroquine and Control (3.7% versus 2.9%; pooled risk ratio 1.22; 95% confidence interval: 0.76-1.96). Conclusion Hydroxychloroquine is not efficacious in reducing mortality of COVID-19 patients. Prospero database registration (www.crd.york.ac.uk/prospero) under number CRD42020197070.

The effects of acute kidney injury in a multicenter cohort of high-risk surgical patients.

BACKGROUND AND OBJECTIVES: Patients who develop post-operative acute kidney injury (AKI) have a poor prognosis, especially when undergoing high-risk surgery. Therefore, the objective of this study was to evaluate the outcome of patients with AKI acquired after non-cardiac surgery and the possible risk factors for this complication. METHODS: A multicenter, prospective cohort study with patients admitted to intensive care units (ICUs) after non-cardiac surgery was conducted to assess whether they developed AKI. The patients who developed AKI were then compared to non-AKI patients. RESULTS: A total of 29 ICUs participated, of which 904 high-risk surgical patients were involved in the study. The occurrence of AKI in the post-operative period was 15.8%, and the mortality rate of post-operative AKI patients at 28 days was 27.6%. AKI was strongly associated with 28-day mortality (OR = 2.91; 95% CI 1.51-5.62; p = 0.001), and a higher length of ICU and hospital stay (p < 0.001). Independent factors for the risk of developing AKI were pre-operative anemia (OR = 7.01; 95% CI 1.69-29.07), elective surgery (OR = 0.45; 95% CI 0.21-0.97), SAPS 3 (OR = 1.04; 95% CI 1.02-1.06), post-operative vasopressor use (OR = 2.47; 95% CI 1.34-4.55), post-operative infection (OR = 8.82; 95% CI 2.43-32.05) and the need for reoperation (OR= 7.15; 95% CI 2.58-19.79). CONCLUSION: AKI was associated with the risk of death in surgical patients and those with anemia before surgery, who had a higher SAPS 3, needed a post-operative vasopressor, or had a post-operative infection or needed reoperation were more likely to develop AKI post-operatively.

International multicentre observational study to evaluate the association between perioperative red blood cell transfusions and 1-year mortality after major cancer surgery (ARCA-1): study design, statistical analysis plan and study protocol.

INTRODUCTION: Blood transfusion is still common in patients undergoing major cancer surgery. Blood transfusion can be associated with poor prognosis in patients with cancer. Perioperative Care in the Cancer Patient -1 (ARCA-1) aims to assess in a large cohort of patients the current incidence, pattern of practice and associations between perioperative blood transfusions and 1-year survival in patients undergoing major cancer surgery. METHODS AND ANALYSIS: ARCA-1 is a prospective international multicentre observational study that will include adult patients scheduled to have major cancer surgical procedures with the intention to cure, and an overnight planned hospital admission. The study will be opened for 1 year for enrolment (7 January 2020-7 February 2021). Each centre will enrol patients for 30 days. The primary endpoint of this study is all-cause mortality 1 year after major cancer surgery. Secondary endpoints are rate of perioperative blood product use, cancer-specific mortality at 1 year and PFSs and 30-day morbidity and mortality. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board at The University of Texas-MD Anderson Cancer Center. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04491409.