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BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared to intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis-when 75% of anticipated participants had completed follow up-the Data and Safety Monitoring Board recommended to terminate the trial, and upon unblinding, the Operations Committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group and in 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5%; 95% CI, -0.9 to 0.03; P = .07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3%; 95% CI, 5.2 to 11.5; P = .007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared to the intravenous group was 8.2% (95% CI, 3.4 to 12.9). CONCLUSIONS: Among patients having cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared to intravenous tranexamic acid.
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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 , Sepse , Adulto , Ácido Ascórbico/efeitos adversos , Humanos , Hipoglicemiantes/uso terapêutico , Unidades de Terapia Intensiva , Insuficiência de Múltiplos Órgãos , Qualidade de Vida , Sepse/tratamento farmacológico , Vasoconstritores/efeitos adversos , Vitaminas/efeitos adversosRESUMO
BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).
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Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , Receptores de Interleucina-6/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , COVID-19/complicações , COVID-19/mortalidade , COVID-19/terapia , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Razão de Chances , Respiração ArtificialRESUMO
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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Injúria Renal Aguda/terapia , Terapia de Substituição Renal , Injúria Renal Aguda/mortalidade , Idoso , Estado Terminal/terapia , Humanos , Análise de Intenção de Tratamento , Pessoa de Meia-Idade , Terapia de Substituição Renal/efeitos adversos , Tempo para o Tratamento , Resultado do TratamentoRESUMO
Rationale: Blood glucose concentrations affect outcomes in critically ill patients, but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objectives: To evaluate the effects of a "liberal" approach to targeted blood glucose range during ICU admission. Methods: This mutlicenter, parallel-group, open-label randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dl and titrated to a target range of 180-252 mg/dl. In the comparator group insulin was commenced at a blood glucose >180 mg/dl and titrated to a target range of 108-180 mg/dl. The primary outcome was incident hypoglycemia (<72 mg/dl). Secondary outcomes included glucose metrics and clinical outcomes. Measurements and Main Results: By Day 28, at least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio, 0.21 [95% confidence interval (CI), 0.09 to 0.49]; P < 0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability, and less relative hypoglycemia (P < 0.001 for all comparisons). By Day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference, 4.6 percentage points [95% CI, -3.9% to 13.2%]; P = 0.29). Conclusions: A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12616001135404).
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Adulto , Austrália , Glicemia , Estado Terminal/terapia , Diabetes Mellitus Tipo 2/complicações , Humanos , Hipoglicemia/complicações , Hipoglicemia/tratamento farmacológico , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
Importance: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. Conclusions and Relevance: Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
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COVID-19 , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Seguimentos , Hidroxicloroquina/uso terapêutico , SARS-CoV-2 , Estado Terminal/terapia , Teorema de Bayes , Soroterapia para COVID-19 , Corticosteroides/uso terapêutico , Anticoagulantes/efeitos adversos , Receptores de Interleucina-6RESUMO
Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Interventions: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Results: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). Conclusions and Relevance: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.
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Tratamento Farmacológico da COVID-19 , COVID-19 , Estado Terminal , Inibidores da Agregação Plaquetária , Tromboembolia Venosa , Adulto , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Teorema de Bayes , COVID-19/complicações , COVID-19/mortalidade , COVID-19/terapia , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Respiração Artificial , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologiaRESUMO
OBJECTIVES: Nonpharmaceutical interventions are implemented internationally to mitigate the spread of severe acute respiratory syndrome coronavirus 2 with the aim to reduce coronavirus disease 2019-related deaths and to protect the health system, particularly intensive care facilities from being overwhelmed. The aim of this study is to describe the impact of nonpharmaceutical interventions on ICU admissions of non-coronavirus disease 2019-related patients. DESIGN: Retrospective cohort study. SETTING: Analysis of all reported adult patient admissions to New Zealand ICUs during Level 3 and Level 4 lockdown restrictions from March 23, to May 13, 2020, in comparison with equivalent periods from 5 previous years (2015-2019). SUBJECTS: Twelve-thousand one-hundred ninety-two ICU admissions during the time periods of interest were identified. MEASUREMENTS: Patient data were obtained from the Australian and New Zealand Intensive Care Society Adult Patient Database, Australian and New Zealand Intensive Care Society critical care resources registry, and Statistics New Zealand. Study variables included patient baseline characteristics and ICU resource use. MAIN RESULTS: Nonpharmaceutical interventions in New Zealand were associated with a 39.1% decrease in ICU admission rates (p < 0.0001). Both elective (-44.2%) and acute (-36.5%) ICU admissions were significantly reduced when compared with the average of the previous 5 years (both p < 0.0001). ICU occupancy decreased from a mean of 64.3% (2015-2019) to 39.8% in 2020. Case mix, ICU resource use per patient, and ICU and hospital mortality remained unchanged. CONCLUSIONS: The institution of nonpharmaceutical interventions was associated with a significant decrease in elective and acute ICU admissions and ICU resource use. These findings may help hospitals and health authorities planning for surge capacities and elective surgery management in future pandemics.
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COVID-19/diagnóstico , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Quarentena/estatística & dados numéricos , Adulto , Idoso , COVID-19/epidemiologia , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Estudos RetrospectivosRESUMO
OBJECTIVES: There is little evidence to guide fluid administration to patients admitted to the ICU following cardiac surgery. This study aimed to determine if a protocolized strategy known to reduce fluid administration when compared with usual care reduced ICU length of stay following cardiac surgery. DESIGN: Prospective, multicenter, parallel-group, randomized clinical trial. SETTING: Five cardiac surgical centers in New Zealand conducted from November 2016 to December 2018 with final follow-up completed in July 2019. PATIENTS: Seven-hundred fifteen patients undergoing cardiac surgery; 358 intervention and 357 usual care. INTERVENTIONS: Randomization to protocol-guided strategy utilizing stroke volume variation to guide administration of bolus fluid or usual care fluid administration until desedation or up to 24 hours. Primary outcome was length of stay in ICU. Organ dysfunction, mortality, process of care measures, patient-reported quality of life, and disability-free survival were collected up to day 180. MEASUREMENTS AND MAIN RESULTS: Overall 666 of 715 (93.1%) received at least one fluid bolus. Patients in the intervention group received less bolus fluid (median [interquartile range], 1,000 mL [250-2,000 mL] vs 1,500 mL [500-2,500 mL]; p < 0.0001) and had a lower overall fluid balance (median [interquartile range], 319 mL [-284 to 1,274 mL] vs 673 mL [38-1,641 mL]; p < 0.0001) in the intervention period. There was no difference in ICU length of stay between the two groups (27.9 hr [21.8-53.5 hr] vs 25.6 hr [21.9-64.6 hr]; p = 0.95). There were no differences seen in development of organ dysfunction, quality of life, or disability-free survival at any time points. Hospital mortality was higher in the intervention group (4% vs 1.4%; p = 0.04). CONCLUSIONS: A protocol-guided strategy utilizing stroke volume variation to guide administration of bolus fluid when compared with usual care until desedation or up to 24 hours reduced the amount of fluid administered but did not reduce the length of stay in ICU.
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Hidratação/métodos , Hemodinâmica/fisiologia , Tempo de Internação/estatística & dados numéricos , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Protocolos Clínicos , Humanos , Unidades de Terapia Intensiva/organização & administração , Masculino , Pessoa de Meia-Idade , Nova ZelândiaRESUMO
Importance: Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The comparative effect of these drugs on mortality is unknown. Objective: To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis. Design, Setting, and Participants: Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital. Interventions: Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13â¯436 patients randomized by site to PPIs and 13â¯392 randomized by site to H2RBs). Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay. Results: Among 26â¯982 patients who were randomized, 154 opted out, and 26â¯828 were analyzed (mean [SD] age, 58 [17.0] years; 9691 [36.1%] were women). There were 26â¯771 patients (99.2%) included in the mortality analysis; 2459 of 13â¯415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13â¯356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 [95% CI, 1.00 to 1.10]; absolute risk difference, 0.93 percentage points [95% CI, -0.01 to 1.88] percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 [95% CI, 0.57 to 0.92]; absolute risk difference, -0.51 percentage points [95% CI, -0.90 to -0.12 percentage points]; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group. Conclusions and Relevance: Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication. Trial Registration: anzctr.org.au Identifier: ACTRN12616000481471.
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Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Úlcera Péptica/prevenção & controle , Inibidores da Bomba de Prótons/uso terapêutico , Respiração Artificial , Adulto , Estudos Cross-Over , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Approximately 9000 patients with type-2 diabetes mellitus (T2DM) are admitted to an intensive care unit (ICU) in Australia and New Zealand annually. For these patients, recent exploratory data suggest that targeting a more liberal blood glucose range during ICU admission may be safe and potentially beneficial. However, the current approach to blood glucose management of patients with T2DM in Australia and New Zealand ICUs is not well described, and there is uncertainty about clinician equipoise for trials of liberal glycaemic control in these patients. AIM: The aim is to describe self-reported blood glucose management in patients with T2DM by intensivists working in Australian and New Zealand ICUs and to establish whether equipoise exists for a trial of liberal versus standard glycaemic control in such patients. METHOD: An online questionnaire of Australia and New Zealand intensivists conducted in July-September 2016. RESULTS: Seventy-one intensivists responded. Forty-five (63%) used a basic nomogram to titrate insulin. Sixty-six (93%) reported that insulin was commenced at blood glucose concentrations >10 mmol/L and titrated to achieve a blood glucose concentration between 6.0 and 10.0 mmol/L. A majority of respondents (75%) indicated that there was insufficient evidence to define optimal blood glucose targets in patients with T2DM, and 59 (83%) were prepared to enrol such patients in a clinical trial to evaluate a more liberal approach. CONCLUSION: A majority of respondents were uncertain about the optimal blood glucose target range for patients with T2DM and would enrol such patients in a comparative trial of conventional versus liberal blood glucose control.
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Glicemia/análise , Estado Terminal , Diabetes Mellitus Tipo 2/sangue , Adulto , Austrália , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Unidades de Terapia Intensiva , Masculino , Nova Zelândia , AutorrelatoRESUMO
BACKGROUND: Cardiac surgery utilizing cardiopulmonary bypass (CPB) is one of the most common forms of major surgery. Cardiac surgery-associated multiorgan dysfunction (CSA-MOD) is well recognized and includes acute kidney injury (AKI), hepatic impairment, myocardial damage, and postoperative neurologic deficit. Pathophysiology of CSA-MOD involves numerous injurious pathways linked to the use of CPB including oxidative stress and formation of reactive iron species. During cardiac surgery with CPB, arterial return blood is oxygenated to supranormal levels. This study aimed to determine whether the avoidance of arterial hyperoxemia decreased oxidative stress and reduced the severity of the multiorgan dysfunction in patients undergoing cardiac surgery utilizing CPB. METHODS: The study was a multicenter, open-label, parallel-group, randomized controlled study of the avoidance of arterial hyperoxemia versus usual care in patients undergoing cardiac surgery involving CPB. Primary outcome was the incidence and severity of AKI. Secondary outcomes included serum biomarkers for CSA-MOD, duration of mechanical ventilation, and length of intensive care and hospital stay. RESULTS: A total of 298 patients were randomized and analyzed at two hospitals in New Zealand and Australia. Mean PaO2 was significantly different between groups during CPB. There was no difference in the development of AKI (intervention arm 72.0% vs. usual care 66.2%; difference, -5.8% [95% CI, -16.1 to 4.7%]; P = 0.28), other markers of organ damage, or intensive care unit and hospital length of stay. CONCLUSIONS: Avoiding modest hyperoxemia during CPB failed to demonstrate any difference in AKI, markers of organ damage, or length of stay.
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Injúria Renal Aguda/epidemiologia , Ponte Cardiopulmonar/efeitos adversos , Hiperóxia/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Injúria Renal Aguda/sangue , Injúria Renal Aguda/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Biomarcadores/sangue , Feminino , Humanos , Hiperóxia/sangue , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/prevenção & controle , Nova Zelândia/epidemiologia , Estresse Oxidativo , Complicações Pós-Operatórias/sangue , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVES: Cardiac surgery-associated acute kidney injury occurs in up to 50% of patients and is associated with increased mortality and morbidity. This study aimed to discover if perioperative urinary alkalinization with sodium bicarbonate infusion reduces the prevalence of cardiac surgery-associated acute kidney injury. DESIGN: This study was a phase IIb multicenter double-blind randomized controlled trial. SETTING: This study was conducted in three tertiary hospitals in New Zealand and Australia. PATIENTS: A total of 427 patients scheduled to undergo elective cardiac surgery, who were at increased risk of development of cardiac surgery-associated acute kidney injury using recognized risk factors. MEASUREMENTS AND MAIN RESULTS: Patients were randomly allocated to receive either sodium bicarbonate (n = 215) or sodium chloride (n = 212) infusion, commencing at the start of anesthesia, in a dose of 0.5 mEq/kg/hr for the first hour and then 0.2 mmol/kg/hr for 23 hours. The primary outcome measure was the number of patients with development of cardiac surgery-associated acute kidney injury, defined as an increase in creatinine greater than 25% or 0.5 mg/dL (44 µmol/L) from baseline to peak value within the first five postoperative days. Significant differences among the groups in both plasma and urinary biochemistry were achieved 6 hours after commencement of the infusion, and these changes persisted for more than 24 hours. A total of 100 out of 215 patients (47% [95% CI, 40%-53%]) in the sodium bicarbonate group and 93 of 212 patients (44% [95% CI, 37%-51%]) in the sodium chloride group with development of acute kidney injury within the first five postoperative days (p = 0.58). There were also no significant differences in ventilation hours, ICU or hospital length of stay, or mortality. CONCLUSIONS: Perioperative alkalinization of blood and urine using an infusion of sodium bicarbonate did not result in a decrease in the prevalence of acute kidney injury in patients following cardiac surgery.
Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Bicarbonato de Sódio/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue , Comorbidade , Creatinina/urina , Método Duplo-Cego , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Cloreto de Sódio/administração & dosagemRESUMO
BACKGROUND: There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). METHODS: We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. RESULTS: We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75-1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66-0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39-0.94). CONCLUSIONS: In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days.
Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Humanos , Injúria Renal Aguda/terapia , Estado Terminal/terapia , Diálise Renal , Terapia de Substituição RenalRESUMO
AIM: Cardiac surgery is the largest perioperative user of donated blood products. There is significant uncertainty as to the optimal threshold for RBC transfusion in patients undergoing cardiac surgery with little evidence to guide practice. We wished to determine whether the results of a large randomised controlled trial had changed practice. METHODS: A prospective observational study of red blood cell (RBC) transfusions of patients undergoing cardiac surgery utilising cardiopulmonary bypass was undertaken as well as a cross-sectional self-administered online practice survey of clinicians ordering red blood cell transfusions in all publicly funded cardiac centres in New Zealand. RESULTS: Significantly more transfusions were administered to a pre-transfusion haemoglobin <75g/L and thus considered in agreement with the restrictive arm of the TRICS III study after completion of TRICS III study enrolment and before results were known (T1)=44% when compared to after results were known (T2=56.7%, p=0.01). Most respondents in the clinician survey had participated in the TRICS III study. CONCLUSIONS: After the publication of the findings of a large multi-national clinical trial, clinicians involved in the care of cardiac surgery patients were more restrictive in their administration of red blood cell transfusions than before the trial findings were published.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Estudos Transversais , Transfusão de Eritrócitos/métodos , Hemoglobinas/análise , Humanos , Nova ZelândiaRESUMO
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an invasive procedure used to support critically ill patients with the most severe forms of cardiac or respiratory failure in the short term, but long-term effects on incidence of death and disability are unknown. We aimed to assess incidence of death or disability associated with ECMO up to 6 months (180 days) after treatment. METHODS: This prospective, multicentre, registry-embedded cohort study was done at 23 hospitals in Australia from Feb 15, 2019, to Dec 31, 2020. The EXCEL registry included all adults (≥18 years) in Australia who were admitted to an intensive care unit (ICU) in a participating centre at the time of the study and who underwent ECMO. All patients who received ECMO support for respiratory failure, cardiac failure, or cardiac arrest during their ICU stay were eligible for this study. The primary outcome was death or moderate-to-severe disability (defined using the WHO Disability Assessment Schedule 2.0, 12-item survey) at 6 months after ECMO initiation. We used Fisher's exact test to compare categorical variables. This study is registered with ClinicalTrials.gov, NCT03793257. FINDINGS: Outcome data were available for 391 (88%) of 442 enrolled patients. The primary outcome of death or moderate-to-severe disability at 6 months was reported in 260 (66%) of 391 patients: 136 (67%) of 202 who received veno-arterial (VA)-ECMO, 60 (54%) of 111 who received veno-venous (VV)-ECMO, and 64 (82%) of 78 who received extracorporeal cardiopulmonary resuscitation (eCPR). After adjustment for age, comorbidities, Acute Physiology and Chronic Health Evaluation (APACHE) IV score, days between ICU admission and ECMO start, and use of vasopressors before ECMO, death or moderate-to-severe disability was higher in patients who received eCPR than in those who received VV-ECMO (VV-ECMO vs eCPR: risk difference [RD] -32% [95% CI -49 to -15]; p<0·001) but not VA-ECMO (VA-ECMO vs eCPR -8% [-22 to 6]; p=0·27). INTERPRETATION: In our study, only a third of patients were alive without moderate-to-severe disability at 6 months after initiation of ECMO. The finding that disability was common across all areas of functioning points to the need for long-term, multidisciplinary care and support for surviving patients who have had ECMO. Further studies are needed to understand the 180-day and longer-term prognosis of patients with different diagnoses receiving different modes of ECMO, which could have important implications for the selection of patients for ECMO and management strategies in the ICU. FUNDING: The National Health and Medical Research Council of Australia.
Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Respiratória , Adulto , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Estudos de Coortes , Incidência , Estudos Prospectivos , Resultado do Tratamento , Insuficiência Respiratória/terapia , Sistema de Registros , Estudos RetrospectivosRESUMO
BACKGROUND: The LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor. OBJECTIVE: We aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database. METHODS: The SAP was designed by the LOVIT principal investigators and statisticians, and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes, and describes the planned primary, secondary, and subgroup analyses. RESULTS: The SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors, or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% CI in a generalized linear mixed model with binomial distribution and log link, with site as a random effect. We will perform a secondary analysis adjusting for prespecified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status. CONCLUSIONS: We have developed an SAP for the LOVIT trial and will adhere to it in the analysis phase. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36261.
RESUMO
BACKGROUND: Nasal high-flow oxygen therapy increases the mean nasopharyngeal airway pressure in adults, but the relationship between flow and pressure is not well defined. OBJECTIVE: To determine the relationship between flow and pressure with the Optiflow nasal high-flow oxygen therapy system. METHODS: We invited patients scheduled for elective cardiac surgery to participate. Measurements were performed with nasal high-flow oxygen at flows of 30, 40, and 50 L/min, with the patient's mouth both open and closed. Pressures were recorded over one minute of breathing, and average flows were calculated via simple averaging. RESULTS: With the mouth closed, the mean ± SD airway pressures at 30, 40, and 50 L/min were 1.93 ± 1.25 cm H(2)O, 2.58 ± 1.54 cm H(2)O, and 3.31 ± 1.05 cm H(2)O, respectively. There was a positive linear relationship between flow and pressure. CONCLUSIONS: The mean nasopharyngeal pressure during nasal high-flow oxygen increases as flow increases. Australian Clinical Trials Registry http://www.adhb.govt.nz/achicu/hot_2_airway_pressure.htm.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Nasofaringe/fisiopatologia , Oxigenoterapia/métodos , Insuficiência Respiratória/terapia , Adulto , Seguimentos , Humanos , Pessoa de Meia-Idade , Pressão , Estudos Prospectivos , Respiração , Insuficiência Respiratória/fisiopatologia , Resultado do TratamentoRESUMO
OBJECTIVE: In a cardiothoracic and vascular intensive care unit, to compare nasal high-flow (NHF) oxygen therapy and standard high-flow face mask (HFFM) oxygen therapy in patients with mild to moderate hypoxemic respiratory failure. METHODS: In a prospective randomized comparative study, 60 patients with mild to moderate hypoxemic respiratory failure were randomized to receive NHF or HFFM. We analyzed the success of allocated therapy, noninvasive ventilation rate, and oxygenation. RESULTS: Significantly more NHF patients succeeded with their allocated therapy (P = .006). The rate of noninvasive ventilation in the NHF group was 3/29 (10%), compared with 8/27 (30%) in the HFFM group (P = .10). The NHF patients also had significantly fewer desaturations (P = .009). CONCLUSIONS: NHF oxygen therapy may be more effective than HFFM in treating mild to moderate hypoxemic respiratory failure.
Assuntos
Cuidados Críticos , Hipóxia/terapia , Oxigenoterapia/instrumentação , Insuficiência Respiratória/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Catéteres , Estudos de Coortes , Feminino , Humanos , Hipóxia/etiologia , Hipóxia/fisiopatologia , Masculino , Máscaras , Pessoa de Meia-Idade , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Mechanical ventilation requires an endotracheal tube. Airway management includes endotracheal suctioning, a frequent procedure for patients in the ICU. Associated risks of endotracheal suctioning include hypoxia, atelectasis, and infection. There is currently no evidence about the safety of avoiding endotracheal suction. We aimed to assess the safety of avoiding endotracheal suction, including at extubation, in cardiac surgical patients who were mechanically ventilated for ≤ 12 h. METHODS: We conducted a single-center, noninferiority, randomized controlled trial in a cardiac ICU in a metropolitan tertiary teaching hospital. Subjects were assigned to either avoidance of endotracheal suction or to usual care including endotracheal suctioning during mechanical ventilation. In total, we screened 468 patients and randomized 249 subjects (usual care, n = 125; intervention, n = 124). Subjects were elective cardiac surgical patients anticipated to receive ≤ 12 h of mechanical ventilation. The primary outcome was the [Formula: see text]/[Formula: see text] on room air 6 h after extubation, with a noninferiority margin of 10% (lower bound of one-sided 95% CI to be < 30). RESULTS: There were no differences in group characteristics at baseline. The primary analysis was a per-protocol analysis performed on 154 subjects. The median [Formula: see text]/[Formula: see text] was 323 for the intervention group and 311 for the standard care group (median difference = 12, one-sided 95% CI -14.3). The results were consistent when using an intention-to-treat analysis and a 97.5% CI. There were no differences between groups in complications or safety measures, including the escalation of oxygen therapy. CONCLUSIONS: Endotracheal suctioning can be safely minimized or avoided in low-risk patients who have had cardiac surgery and are expected to be ventilated for < 12 h after surgery.