RESUMO
OBJECTIVE: Patients with acute respiratory failure often require mechanical ventilation to reduce the work of breathing and improve gas exchange; however, this may exacerbate lung injury. Protective ventilation strategies, characterized by low tidal volumes (≤ 8mL/kg of predicted body weight) and limited plateau pressure below 30cmH2O, have shown improved outcomes in patients with acute respiratory distress syndrome. However, in the transition to spontaneous ventilation, it can be challenging to maintain tidal volume within protective levels, and it is unclear whether low tidal volumes during spontaneous ventilation impact patient outcomes. We developed a study protocol to estimate the prevalence of low tidal volume ventilation in the first 24 hours of spontaneous ventilation in patients with hypoxemic acute respiratory failure and its association with ventilator-free days and survival. METHODS: We designed a multicenter, multinational, cohort study with a 28-day follow-up that will include patients with acute respiratory failure, defined as a partial oxygen pressure/fraction of inspired oxygen ratio < 300mmHg, in transition to spontaneous ventilation in intensive care units in Latin America. RESULTS: We plan to include 422 patients in ten countries. The primary outcomes are the prevalence of low tidal volume in the first 24 hours of spontaneous ventilation and ventilator-free days on day 28. The secondary outcomes are intensive care unit and hospital mortality, incidence of asynchrony and return to controlled ventilation and sedation. CONCLUSION: In this study, we will assess the prevalence of low tidal volume during spontaneous ventilation and its association with clinical outcomes, which can inform clinical practice and future clinical trials.
Assuntos
Unidades de Terapia Intensiva , Síndrome do Desconforto Respiratório , Volume de Ventilação Pulmonar , Humanos , América Latina/epidemiologia , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/mortalidade , Respiração Artificial , Insuficiência Respiratória/terapia , Insuficiência Respiratória/epidemiologiaRESUMO
BACKGROUND: Norepinephrine (NE) is a cornerstone drug in the management of septic shock, with its dose being used clinically as a marker of disease severity and as mortality predictor. However, variations in NE dose reporting either as salt formulations or base molecule may lead to misinterpretation of mortality risks and hinder the process of care. METHODS: We conducted a retrospective analysis of the MIMIC-IV database to assess the impact of NE dose reporting heterogeneity on mortality prediction in a cohort of septic shock patients. NE doses were converted from the base molecule to equivalent salt doses, and their ability to predict 28-day mortality at common severity dose cut-offs was compared. RESULTS: 4086 eligible patients with septic shock were identified, with a median age of 68 [57-78] years, an admission SOFA score of 7 [6-10], and lactate at diagnosis of 3.2 [2.4-5.1] mmol/L. Median peak NE dose at day 1 was 0.24 [0.12-0.42] µg/kg/min, with a 28-day mortality of 39.3%. The NE dose showed significant heterogeneity in mortality prediction depending on which formulation was reported, with doses reported as bitartrate and tartrate presenting 65 (95% CI 79-43)% and 67 (95% CI 80-47)% lower ORs than base molecule, respectively. This divergence in prediction widened at increasing NE doses. When using a 1 µg/kg/min threshold, predicted mortality was 54 (95% CI 52-56)% and 83 (95% CI 80-87)% for tartrate formulation and base molecule, respectively. CONCLUSIONS: Heterogeneous reporting of NE doses significantly affects mortality prediction in septic shock. Standardizing NE dose reporting as base molecule could enhance risk stratification and improve processes of care. These findings underscore the importance of consistent NE dose reporting practices in critical care settings.
Assuntos
Norepinefrina , Choque Séptico , Humanos , Choque Séptico/tratamento farmacológico , Choque Séptico/mortalidade , Idoso , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Norepinefrina/administração & dosagem , Vasoconstritores/uso terapêutico , Vasoconstritores/administração & dosagem , Estudos de CoortesRESUMO
INTRODUCTION: During acute kidney injury (AKI) due to sepsis, the intestinal microbiota changes to dysbiosis, which affects the kidney function recovery (KFR) and amplifies the injury. Therefore, the administration of probiotics could improve dysbiosis and thereby increase the probability of KFR. METHODS: In this double-blind clinical trial, patients with AKI associated with sepsis were randomized (1:1) to receive probiotics or placebo for 7 consecutive days, with the objectives of evaluate the effect on KFR, mortality, kidney replacement therapy (KRT), urea, urine volume, serum electrolytes and adverse events at day 7. RESULTS: From February 2019 to March 2022, a total of 92 patients were randomized, 48 to the Probiotic and 44 to Placebo group. When comparing with placebo, those in the Probiotics did not observe a higher KFR (HR 0.93, 0.52-1.68, p = 0.81), nor was there a benefit in mortality at 6 months (95% CI 0.32-1.04, p = 0.06). With probiotics, urea values decreased significantly, an event not observed with placebo (from 154 to 80 mg/dl, p = 0.04 and from 130 to 109 mg/dl, p = 0.09, respectively). Urinary volume, need for KRT, electrolyte abnormalities, and adverse events were similar between groups. (ClinicalTrial.gov NCT03877081) (registered 03/15/2019). CONCLUSION: In AKI related to sepsis, probiotics for 7 consecutive days did not increase the probability of KFR, nor did other variables related to clinical improvement, although they were safe.
Assuntos
Injúria Renal Aguda , Probióticos , Sepse , Humanos , Disbiose , Injúria Renal Aguda/terapia , Probióticos/uso terapêutico , Sepse/complicações , Sepse/tratamento farmacológico , UreiaRESUMO
PURPOSE OF REVIEW: The ANDROMEDA-SHOCK trial positioned capillary refill time (CRT) assessment as a novel resuscitation target for septic shock.The purpose of this article is to summarize pathophysiological determinants of CRT, review new technical developments on peripheral perfusion assessment, and explore recent evidence on the role of CRT monitoring in septic shock and other critical conditions. RECENT FINDINGS: A growing body of evidence supports the role of peripheral perfusion assessment as a warning and prognostic signal in a variety of clinical conditions among severely ill patients. Recent physiological studies demonstrated a rapid improvement of CRT after a single fluid bolus or a passive leg raising maneuver, a fact which may have diagnostic and therapeutic implications. Moreover, a couple of posthoc analyses of ANDROMEDA-SHOCK trial, reinforce that a normal CRT at the start of septic shock resuscitation, or its rapid normalization, thereafter may be associated with significant better outcomes. SUMMARY: Recent data confirm the relevance of peripheral perfusion assessment in septic shock and other conditions in critically ill patients. Future studies should confirm these findings, and test the potential contribution of technological devices to assess peripheral perfusion.
Assuntos
Perfusão , Ressuscitação , Choque Séptico , Humanos , Ressuscitação/métodos , Hemodinâmica , Estado TerminalRESUMO
PURPOSE: Methylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its' optimal timing, dosing and safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock. METHODS: In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days. RESULTS: Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration. CONCLUSION: In patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials. Trial registration ClinicalTrials.gov registration number NCT04446871 , June 25, 2020, retrospectively registered.
Assuntos
Sepse , Choque Séptico , Humanos , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Vasoconstritores/uso terapêutico , Sepse/complicaçõesRESUMO
Resumen: Introducción: La mayoría de los pacientes con COVID-19 mecánicamente ventilados cumplen con los criterios de Berlín para síndrome de distrés respiratorio agudo (SDRA); sin embargo, se ha observado una discrepancia entre el grado de hipoxemia y la distensibilidad pulmonar. Basados en la mecánica respiratoria y hallazgos tomográficos se han propuesto dos fenotipos distintos: L y H, cada fenotipo podría beneficiarse de estrategias de ventilación distintas; sin embargo, realizar tomografías durante la pandemia resulta complicado. Objetivo: Determinar la utilidad del ultrasonido pulmonar para diferenciar los fenotipos del SDRA por COVID-19 mediante la correlación de lung ultrasound score (LUS) y la distensibilidad del sistema respiratorio. Material y métodos: Analizamos de forma prospectiva pacientes con COVID-19 bajo ventilación mecánica invasiva a su ingreso a la unidad de cuidados intensivos (UCI). Resultados: De un total de 90 pacientes, 62% hombres, mediana 60 años, SOFA siete puntos. La incidencia del fenotipo H fue 83.3%. El puntaje de aireación (LUS) tuvo una diferencia significativa entre ambos fenotipos (p = 0.001), con un área bajo la curva de 0.797 (p < 0.001). Con punto de corte para la predicción del fenotipo H: LUS > 18 puntos (sensibilidad 82.6%, especificidad 73.3%). Conclusión: El ultrasonido pulmonar valora de forma confiable el grado de aireación pulmonar y junto con la distensibilidad permite clasificar por fenotipos a los pacientes con SDRA por COVID-19.
Abstract: Introduction: Most mechanically ventilated COVID-19 patients meet the Berlin criteria for acute respiratory distress syndrome (ARDS), however, a discrepancy between the degree of hypoxemia and pulmonary distensibility has been observed. Based on respiratory mechanics and tomographic findings two distinct phenotypes have been proposed: L and H, each phenotype could benefit from distinct ventilation strategies, however, performing tomographic scans during pandemic is complicated. Objective: To determine the usefulness of lung ultrasound to differentiate ARDS phenotypes by COVID-19, by correlating LUS and respiratory system distensibility. Material and methods: We prospectively analyzed patients with COVID-19 under invasive mechanical ventilation on admission to the ICU. Results: Of a total of 90 patients, 62% men, median 60 years, SOFA 7 points. The incidence of phenotype H was 83.3%. LUS had a significant difference between both phenotypes (p = 0.001), with an area under the curve of 0.797 (p < 0.001). With cutoff point for phenotype H prediction: LUS >18 points (sensitivity 82.6%, specificity 73.3%). Conclusion: Lung ultrasound reliably assesses the degree of pulmonary aeration and, together with distensibility, allows the classification of patients with ARDS by COVID-19 phenotypes.
Resumo: Introdução: A maioria dos pacientes com COVID-19 ventilados mecanicamente atende aos critérios de Berlim para SDRA, no entanto, foi observada uma discrepância entre o grau de hipoxemia e a complacência pulmonar. Com base na mecânica respiratória e nos achados tomográficos, dois fenótipos diferentes foram propostos: L e H, cada fenótipo poderia se beneficiar de diferentes estratégias de ventilação, porém, realizar a tomografia durante a pandemia é complicado. Objetivo: Determinar a utilidade da ultrassonografia pulmonar para diferenciar os fenótipos de SDRA por COVID-19, correlacionando LUS e complacência do sistema respiratório. Material e métodos: Analisamos prospectivamente pacientes com COVID-19 sob ventilação mecânica invasiva na admissão à UTI. Resultados: De um total de 90 pacientes, 62% homens, idade média de 60 anos, SOFA 7 pontos. A incidência do fenótipo H foi de 83.3%. O LUS apresentou diferença significativa entre os dois fenótipos (p = 0.001), com área sob a curva de 0.797 (p < 0.001). Com ponto de corte para a predição do fenótipo H: LUS > 18 pontos (sensibilidade 82.6%, especificidade 73.3%). Conclusão: A ultrassonografia pulmonar avalia de forma confiável o grau de aeração pulmonar e, juntamente com a distensibilidade, permite que os pacientes com SDRA por COVID-19 sejam classificados por fenótipos.
RESUMO
BACKGROUND: Awake prone positioning (APP) improves oxygenation in coronavirus disease (COVID-19) patients and, when successful, may decrease the risk of intubation. However, factors associated with APP success remain unknown. In this secondary analysis, we aimed to assess whether APP can reduce intubation rate in patients with COVID-19 and to focus on the factors associated with success. METHODS: In this multicenter randomized controlled trial, conducted in three high-acuity units, we randomly assigned patients with COVID-19-induced acute hypoxemic respiratory failure (AHRF) requiring high-flow nasal cannula (HFNC) oxygen to APP or standard care. Primary outcome was intubation rate at 28 days. Multivariate analyses were performed to identify the predictors associated to treatment success (survival without intubation). RESULTS: Among 430 patients randomized, 216 were assigned to APP and 214 to standard care. The APP group had a lower intubation rate (30% vs 43%, relative risk [RR] 0.70; CI95 0.54-0.90, P = 0.006) and shorter hospital length of stay (11 interquartile range [IQR, 9-14] vs 13 [IQR, 10-17] days, P = 0.001). A respiratory rate ≤ 25 bpm at enrollment, an increase in ROX index > 1.25 after first APP session, APP duration > 8 h/day, and a decrease in lung ultrasound score ≥ 2 within the first 3 days were significantly associated with treatment success for APP. CONCLUSION: In patients with COVID-19-induced AHRF treated by HFNC, APP reduced intubation rate and improved treatment success. A longer APP duration is associated with APP success, while the increase in ROX index and decrease in lung ultrasound score after APP can also help identify patients most likely to benefit. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov at July 20, 2021. Identification number NCT04477655. https://clinicaltrials.gov/ct2/show/NCT04477655?term=PRO-CARF&draw=2&rank=1.
Assuntos
COVID-19 , Insuficiência Respiratória , COVID-19/complicações , COVID-19/terapia , Cânula , Humanos , Decúbito Ventral , Insuficiência Respiratória/complicações , Insuficiência Respiratória/terapia , VigíliaRESUMO
AIM: The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF). METHODS: In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion. RESULTS: From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53). CONCLUSION: In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.
Assuntos
Síndrome Cardiorrenal/tratamento farmacológico , Síndrome Cardiorrenal/fisiopatologia , Diuréticos/administração & dosagem , Adulto , Clortalidona/administração & dosagem , Clortalidona/efeitos adversos , Diuréticos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Furosemida/administração & dosagem , Furosemida/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Espironolactona/administração & dosagem , Espironolactona/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVES: Airway pressure release ventilation is a ventilatory mode characterized by a mandatory inverse inspiratory:expiratory ratio with a very short expiratory phase, aimed to avoid derecruitment and allow spontaneous breathing. Recent basic and clinical evidence suggests that this mode could be associated with improved outcomes in patients with acute respiratory distress syndrome. The aim of this study was to compare the outcomes between airway pressure release ventilation and traditional ventilation targeting low tidal volume, in patients with severe coronavirus disease 2019. DESIGN: Single-center randomized controlled trial. SETTING: ICU of a Mexican referral center dedicated to care of patients with confirmed diagnosis of coronavirus disease 2019. PATIENTS: Ninety adult intubated patients with acute respiratory distress syndrome associated with severe coronavirus disease 2019. INTERVENTIONS: Within 48 hours after intubation, patients were randomized to either receive ventilatory management with airway pressure release ventilation or continue low tidal volume ventilation. MEASUREMENTS AND MAIN RESULTS: Forty-five patients in airway pressure release ventilation group and 45 in the low tidal volume group were included. Ventilator-free days were 3.7 (0-15) and 5.2 (0-19) in the airway pressure release ventilation and low tidal volume groups, respectively (p = 0.28). During the first 7 days, patients in airway pressure release ventilation had a higher Pao2/Fio2 (mean difference, 26 [95%CI, 13-38]; p < 0.001) and static compliance (mean difference, 3.7 mL/cm H2O [95% CI, 0.2-7.2]; p = 0.03), higher mean airway pressure (mean difference, 3.1 cm H2O [95% CI, 2.1-4.1]; p < 0.001), and higher tidal volume (mean difference, 0.76 mL/kg/predicted body weight [95% CI, 0.5-1.0]; p < 0.001). More patients in airway pressure release ventilation had transient severe hypercapnia, defined as an elevation of Pco2 at greater than or equal to 55 along with a pH less than 7.15 (42% vs 15%; p = 0.009); other outcomes were similar. Overall mortality was 69%, with no difference between the groups (78% in airway pressure release ventilation vs 60% in low tidal volume; p = 0.07). CONCLUSIONS: In conclusion, when compared with low tidal volume, airway pressure release ventilation was not associated with more ventilator-free days or improvement in other relevant outcomes in patients with severe coronavirus disease 2019.
Assuntos
COVID-19/complicações , Pressão Positiva Contínua nas Vias Aéreas , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Adulto , Idoso , COVID-19/mortalidade , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Volume de Ventilação PulmonarRESUMO
Resumen: Introducción: preeclampsia, la complicación más común del embarazo, ocasiona más de 76,000 muertes maternas al año, principalmente por complicaciones neurológicas. La alteración en la vasorregulación cerebral es clave en la patogénesis de dichas complicaciones. La ecografía Doppler transcraneal (EDT) evalúa el flujo de las principales arterias cerebrales, pero se desconocen los cambios que presentan las pacientes con preeclampsia/eclampsia. Objetivo: descripción de los cambios en el flujo sanguíneo cerebral evaluados mediante EDT en pacientes con preeclampsia/eclampsia. Material y métodos: se realizó EDT a las pacientes con diagnóstico de preeclampsia y/o eclampsia atendidas de forma consecutiva en la Unidad de Cuidados Intensivos del Hospital Civil de Guadalajara, del 01 de marzo de 2019 al 01 de marzo de 2021 y grupo control de embarazadas sanas; describimos el patrón de flujo de las arterias cerebrales anterior, media, posterior y arteria basilar. Resultados: Ochenta pacientes, 50 con preeclampsia/eclampsia y 30 embarazadas sanas, edad 23 ± 6.7, 50% primigestas, 34.8 ± 4.3 semanas de gestación. La presión de perfusión cerebral de las arterias cerebrales media derecha > 74 mmHg (sensibilidad 0.88, especificidad 0.86, ABC 0.92) y anterior derecha > 69 mmHg (sensibilidad 0.89, especificidad 0.93, ABC 0.92) tuvieron la mayor asociación con preeclampsia/eclampsia. El índice de flujo sanguíneo de las arterias cerebrales posteriores tuvo asociación significativa con eclampsia (p = 0.02), ABC: 0.695 (p = 0.009), punto de corte ≥ 34.6 cm/s (sensibilidad 1.0, especificidad 0.43, OR 26). Conclusiones: un incremento generalizado de la presión de perfusión es el hallazgo más común en preeclampsia/eclampsia. Aumento en el índice de flujo sanguíneo en las arterias cerebrales posteriores se asocia a complicaciones neurológicas graves en pacientes con preeclampsia.
Abstract: Introduction: preeclampsia, the most common complication of pregnancy, leads to > 76,000 maternal deaths annually, mainly due to neurological complications. An alteration in cerebral vasoregulation is key in the pathogenesis of these complications. Transcranial Doppler Ultrasound (TCD) evaluates the flow of the main cerebral arteries and could help to predict the development of preeclampsia/eclampsia and its complications. Objective: to determine the most frequent cerebral blood flow changes in preeclampsia/eclampsia. Material and methods: we prospectively analyzed by TCD patients with preeclampsia/eclampsia on admission to the ICU. Results: Eighty patients, 50 with preeclampsia/eclampsia and 30 healthy pregnant women, age 23 ± 6.7, 50% primigravida, 34.8 ± 4.3 weeks gestation. Cerebral perfusion pressure of right middle cerebral arteries > 74 mmHg (sensitivity 0.88, specificity 0.86, AUC 0.92) and right anterior cerebral arteries > 69 mmHg (sensitivity 0.89, specificity 0.93, AUC 0.92), had the highest association with preeclampsia/eclampsia. Posterior cerebral artery blood flow index had significant association with eclampsia (p = 0.02), AUC 0.695 (p = 0.009), with a cut-off ≥ 34.6 cm/s (sensitivity 1.0, specificity 0.43, OR 26). Conclusions: a generalized increase in perfusion pressure is the most common finding in preeclampsia/eclampsia. Hyper flow in the posterior cerebral arteries may predict severe neurological complications.
Resumo: Introdução: a pré-eclâmpsia, complicação mais comum da gravidez, causa mais de 76,000 mortes maternas anualmente, principalmente devido a complicações neurológicas. A vasorregulação cerebral alterada é fundamental na patogênese dessas complicações. A ultrassonografia Doppler transcraniana (DTC) avalia o fluxo das principais artérias cerebrais, as alterações que os pacientes com pré-eclâmpsia/eclâmpsia apresentam são desconhecidas. Objetivo: descrição das alterações do fluxo sanguíneo cerebral avaliados por DTC em pacientes com pré-eclâmpsia/eclâmpsia. Material e métodos: DTC foi realizado em pacientes com diagnóstico de pré-eclâmpsia e/ou eclâmpsia tratados consecutivamente na unidade de terapia intensiva do Hospital Civil de Guadalajara, de 1o de março de 2019 a 1o de março de 2021 e um grupo controle de gestantes saudáveis; descrevemos o padrão de fluxo das artérias cerebrais anterior, média, posterior e da artéria basilar. Resultados: 80 pacientes, 50 com pré-eclâmpsia/eclâmpsia e 30 gestantes saudáveis, idade 23 ± 6.7, 50% primíparas, 34.8 ± 4.3 semanas de gestação. A pressão de perfusão cerebral das artérias cerebrais médias direitas > 74 mmHg (sensibilidade 0.88, especificidade 0.86, AUC 0.92) e anterior direita > 69 mmHg (sensibilidade 0.89, especificidade 0.93, AUC 0.92), teve a maior associação com pré-eclâmpsia/eclâmpsia. O índice de fluxo sanguíneo das artérias cerebrais posteriores, teve associação significativa com eclâmpsia (p = 0.02), AUC: 0.695 (p = 0.009), ponto de corte ≥ 34.6 cm/s (sensibilidade 1.0, especificidade 0.43, OR 26). Conclusões: Um aumento generalizado da pressão de perfusão é o achado mais comum na pré-eclâmpsia/eclâmpsia. O aumento da taxa de fluxo sanguíneo nas artérias cerebrais posteriores está associado a complicações neurológicas graves em pacientes com pré-eclâmpsia.
Assuntos
COVID-19 , Humanos , Intubação Intratraqueal , Posicionamento do Paciente , Decúbito Ventral , SARS-CoV-2RESUMO
BACKGROUND: Awake prone positioning has been reported to improve oxygenation for patients with COVID-19 in retrospective and observational studies, but whether it improves patient-centred outcomes is unknown. We aimed to evaluate the efficacy of awake prone positioning to prevent intubation or death in patients with severe COVID-19 in a large-scale randomised trial. METHODS: In this prospective, a priori set up and defined, collaborative meta-trial of six randomised controlled open-label superiority trials, adults who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure due to COVID-19 were randomly assigned to awake prone positioning or standard care. Hospitals from six countries were involved: Canada, France, Ireland, Mexico, USA, Spain. Patients or their care providers were not masked to allocated treatment. The primary composite outcome was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. The six trials are registered with ClinicalTrials.gov, NCT04325906, NCT04347941, NCT04358939, NCT04395144, NCT04391140, and NCT04477655. FINDINGS: Between April 2, 2020 and Jan 26, 2021, 1126 patients were enrolled and randomly assigned to awake prone positioning (n=567) or standard care (n=559). 1121 patients (excluding five who withdrew from the study) were included in the intention-to-treat analysis. Treatment failure occurred in 223 (40%) of 564 patients assigned to awake prone positioning and in 257 (46%) of 557 patients assigned to standard care (relative risk 0·86 [95% CI 0·75-0·98]). The hazard ratio (HR) for intubation was 0·75 (0·62-0·91), and the HR for mortality was 0·87 (0·68-1·11) with awake prone positioning compared with standard care within 28 days of enrolment. The incidence of prespecified adverse events was low and similar in both groups. INTERPRETATION: Awake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula. FUNDING: Open AI inc, Rice Foundation, Projet Hospitalier de Recherche Clinique Interrégional, Appel d'Offre 2020, Groupement Interrégional de Recherche Clinique et d'Innovation Grand Ouest, Association pour la Promotion à Tours de la Réanimation Médicale, Fond de dotation du CHRU de Tours, Fisher & Paykel Healthcare Ltd.
Assuntos
COVID-19 , Posicionamento do Paciente , Decúbito Ventral , Insuficiência Respiratória , Adulto , COVID-19/terapia , Canadá , França , Humanos , Irlanda , México , Estudos Prospectivos , Insuficiência Respiratória/terapia , SARS-CoV-2 , Espanha , Resultado do Tratamento , Estados Unidos , VigíliaRESUMO
BACKGROUND: There is no treatment for septic acute kidney injury (sAKI). The anti-inflammatory activity of prolonged-release pirfenidone (PR-PFD) could be beneficial in this clinical setting. METHODS: This study was a double-blind randomized clinical trial in sAKI patients with nephrology consultation at the Civil Hospital of Guadalajara, in addition to the usual treatment of AKI associated with sepsis; patients were randomized to receive either PR-PFD at 1,200 mg/day (group A) or 600 mg/day (group B) or a matched placebo for 7 consecutive days. The primary objective was the decrease in serum creatinine (sCr) and increase in urinary volume (UV); the secondary objectives were changes in serum electrolytes, acid-base status, and mortality. RESULTS: Between August 2016 and August 2017, 88 patients were randomized. The mean age was 54 (17 ± SD) years, and 47% were male. The main site of infection was the lung (39.8%), septic shock was present in 39.1% of the cases, and the mean SOFA score was 8.8 points. 28 patients received PFD 1,200 mg, 30 patients received PFD 600 mg, and 30 patients received placebo. During the study, sCr did not differ among the groups. The reversion rate of sCr, UV, and mortality was not different among the groups (p=0.70, p=0.47, and p=0.38, respectively). Mild adverse events were not different among the groups. CONCLUSION: PR-PFD did not improve the clinical course of sAKI and seemed to be safe in terms of adverse events. This trial is registered with NCT02530359.
RESUMO
OBJECTIVES: To assess the effect of prone positioning therapy on intubation rate in awake patients with COVID-19 and acute respiratory failure. TRIAL DESIGN: This is a two-center parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hospital Civil de Guadalajara and Hospital General de Occidente in Mexico for COVID-19 associated acute respiratory failure and in need of supplementary oxygen through high-flow nasal cannula are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the COVID-19 unit who test positive for COVID-19 by PCR-test and in need for oxygen are eligible for inclusion. Randomization starts upon identification of requirement of a fraction of inspired oxygen ≥30% for an oxygen capillary saturation of ≥90% Exclusion criteria: less than 18 years-old, pregnancy, patients with immediate need of invasive mechanical ventilation (altered mental status, fatigue), vasopressor requirement to maintain median arterial pressure >65 mmHg, contraindications for prone positioning therapy (recent abdominal or thoracic surgery or trauma, facial, pelvic or spine fracture, untreated pneumothorax, do-not-resuscitate or do-not-intubate order, refusal or inability of the patient to enroll in the study. INTERVENTION AND COMPARATOR: Patients of the intervention group will be asked to remain in a prone position throughout the day as long as possible, with breaks according to tolerance. Pillows will be offered for maximizing comfort at chest, pelvis and knees. Monitoring of vital signs will not be suspended. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of 92%-95%. For patients in the control group, prone positioning will be allowed as a rescue therapy. Staff intensivists will monitor the patient's status in both groups on a 24/7 basis. All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: Endotracheal intubation rate for mechanical ventilation at 28 days. RANDOMISATION: Patients will be randomly allocated to either prone positioning or control group at 1:1 ratio. Such randomization will be computer generated and stratified by center with permuted blocks and length of 4. BLINDING (MASKING): Due to logistical reasons, only principal investigators and the data analyst will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): With an intubation rate of 60% according to recent reports from some American centers, and assuming a decrease to 40% to be clinically relevant, we calculated a total of 96 patients per group, for a beta error of 0.2, and alpha of 0.5. Therefore, we plan to recruit 200 patients, accounting for minimal losses to follow up, with 100 non-intubated patients in the prone position group and a 100 in the control group. TRIAL STATUS: The local registration number is 048-20, with the protocol version number 2.0. The date of approval is 3rd May 2020. Recruitment started on 3rd May and is expected to end in December 2020. TRIAL REGISTRATION: The protocol was retrospectively registered under the title: "Prone Positioning in Non-intubated Patients With COVID-19 Associated Acute Respiratory Failure. The PRO-CARF trial" in ClinicalTrials.gov with the registration number: NCT04477655. Registered on 20 July 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).
Assuntos
Infecções por Coronavirus/complicações , Intubação Intratraqueal/instrumentação , Oxigênio/uso terapêutico , Pneumonia Viral/complicações , Decúbito Ventral/fisiologia , Insuficiência Respiratória/etiologia , Doença Aguda , Adulto , Betacoronavirus/genética , COVID-19 , Cânula/efeitos adversos , Cânula/provisão & distribuição , Estudos de Casos e Controles , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Hospitalização , Humanos , Intubação Intratraqueal/estatística & dados numéricos , Masculino , México/epidemiologia , Oxigênio/administração & dosagem , Oxigênio/sangue , Oxigênio/provisão & distribuição , Pandemias , Posicionamento do Paciente/métodos , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , SARS-CoV-2RESUMO
AIM: To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes. METHODS: This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone. It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31st, 2016. Demographic data, comorbidities, medical management details, adverse effects related to corticosteroids, and outcomes were collected after the critical care physician indicated initiation of hydrocortisone. Univariate comparison between continuous and bolus administration of hydrocortisone was performed, including multivariate analysis, as well as Kaplan-Meier analysis to compare the proportion of shock reversal at 7 d after presentation. Receiver operating characteristic (ROC) curves determined the best cut-off criteria for initiation of hydrocortisone associated with the highest probability of shock reversal. We addressed the effects of the taper strategy for discontinuation of hydrocortisone, noting risk of shock relapse and adverse effects. RESULTS: All-cause 30-d mortality was 42%. Hydrocortisone was administered as a continuous infusion in 54.2% of patients; time to reversal of shock was 49 h longer in patients who were given a bolus administration [59 h (range, 47.5-90.5) vs 108 h (range, 63.2-189); P = 0.001]. The maximal dose of norepinephrine after initiation of hydrocortisone was lower in patients on continuous infusion [0.19 µg/kg per minute (range, 0.11-0.28 µg)] compared with patients who were given bolus [0.34 µg/kg per minute (range, 0.16-0.49); P = 0.004]. Kaplan-Meier analysis revealed a higher proportion of shock reversal at 7 d in patients with continuous infusion compared to those given bolus (83% vs 63%; P = 0.004). There was a good correlation between time to initiation of hydrocortisone and time to reversal of shock (r = 0.80; P < 0.0001); ROC curve analysis revealed that the best criteria for prediction of shock reversal was a time to initiation of hydrocortisone of ≤ 13 h after administration of norepinephrine, with an area under the curve of 0.81 (P < 0.001). The maximal dose of norepinephrine at initiation of hydrocortisone with the highest association with shock reversal was ≤ 0.28 µg/kg per minute, with an area under the curve of 0.75 (P = 0.0002). On a logistic regression model, hydrocortisone taper was not associated with a lower risk of shock relapse (RR = 1.29; P = 0.17) but was related to a higher probability of hyperglycemia [odds ratio (OR), 5.3; P = 0.04] and hypokalemia (OR = 10.6; P = 0.01). CONCLUSION: Continuous infusion of hydrocortisone could hasten the resolution of septic shock compared to bolus administration. Earlier initiation corresponds with a higher probability of shock reversal. Tapering strategy is unnecessary.
RESUMO
OBJECTIVE: The aim of this study was to review clinical data and outcomes of patients with burns in a Mexican non-burn intensive care unit (ICU). METHODS: We did a retrospective analysis of our single-centre database of burn patients admitted to the ICU in the Hospital Civil Fray Antonio Alcalde (University Hospital). The sample was divided for analysis into two groups according to the outcome 'death' or 'discharge' from ICU. RESULTS: Overall mortality was 58.2%, without a decreasing trend in mortality rates through the years. We identified the presence of third-degree burns (odds ratio (OR) 1.5, p=0.003), and >49% total burned surface area (TBSA; OR 3.3, p≤0.001) was associated with mortality. Mean age was higher in deceased patients (38.2 years vs. 31.3 years, p=0.003) as was the TBSA (62.8% vs. 36.4%, p≤0.001). At multivariate analysis, inhalation injury was not associated with increased mortality, but it was with more mechanical ventilation days. Early surgical debridement/cleansing was performed in most patients; however, the mean of the procedures was 1.7 per patient in both groups. CONCLUSION: We identified significant factors associated with mortality. These variables and prognosis from non-burn ICUs differ broadly compared with burn intensive care units (BICUs); thus, more structured, multidisciplinary and specialised treatment strategies are still needed.