RESUMO
OBJECTIVES: An association between physical inactivity and worse outcome during infectious disease has been reported. The effect of moderate exercise preconditioning on the immune response during an acute pneumonia in a murine model was evaluated. SETTING: Laboratory experiments. SUBJECTS: C57BL6/j male mice. INTERVENTIONS: Six-week-old C57BL/6J mice were divided in two groups: an exercise group and a control group. In the exercise group, a moderate, progressive, and standardized physical exercise was applied for 8 weeks. It consisted in a daily treadmill training lasting 60 minutes and with an intensity of 65% of the maximal theoretical oxygen uptake. Usual housing recommendation were applied in the control group during the same period. After 8 weeks, pneumonia was induced in both groups by intratracheal instillation of a fixed concentration of a Klebsiella pneumoniae (5 × 103 colony-forming unit) solution. MEASUREMENTS AND MAIN RESULTS: Mice preconditioned by physical exercise had a less sever onset of pneumonia as shown by a significant decrease of the Mouse Clinical Assessment Severity Score and had a significantly lower mortality compared with the control group (27% vs. 83%; p = 0.019). In the exercise group, we observed a significantly earlier but transient recruitment of inflammatory immune cells with a significant increase of neutrophils, CD4+ cells and interstitial macrophages counts compared with control group. Lung tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-10 were significantly decreased at 48 hours after pneumonia induction in the exercise group compared with the control group. CONCLUSIONS: In our model, preconditioning by moderate physical exercise improves outcome by reducing the severity of acute pneumonia with an increased but transient activation of the innate immune response.
Assuntos
Pneumonia , Camundongos , Masculino , Humanos , Animais , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Pulmão/patologia , Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. METHODS: Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. RESULTS: A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. CONCLUSION: In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).
Assuntos
Procedimentos Cirúrgicos Cardíacos , Delírio , Dexmedetomidina , Delírio do Despertar , Adulto , Humanos , Delírio do Despertar/induzido quimicamente , Delírio do Despertar/tratamento farmacológico , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Delírio/tratamento farmacológico , Delírio/etiologia , Delírio/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Método Duplo-CegoRESUMO
BACKGROUND: Identifying patients at risk of secondary neurologic deterioration (SND) after moderate traumatic brain injury (moTBI) is a challenge, as such patients will need specific care. No simple scoring system has been evaluated to date. This study aimed to determine clinical and radiological factors associated with SND after moTBI and to propose a triage score. METHODS: All adults admitted in our academic trauma center between January 2016 and January 2019 for moTBI (Glasgow Coma Scale [GCS] score, 9-13) were eligible. SND during the first week was defined either by a decrease in GCS score of >2 points from the admission GCS in the absence of pharmacologic sedation or by a deterioration in neurologic status associated with an intervention, such as mechanical ventilation, sedation, osmotherapy, transfer to the intensive care unit (ICU), or neurosurgical intervention (for intracranial mass lesions or depressed skull fracture). Clinical, biological, and radiological independent predictors of SND were identified by logistic regression (LR). An internal validation was performed using a bootstrap technique. A weighted score was defined based on beta (ß) coefficients of the LR. RESULTS: A total of 142 patients were included. Forty-six patients (32%) showed SND, and 14-day mortality rate was 18.4%. Independent variables associated with SND were age above 60 years (odds ratio [OR], 3.45 [95% confidence interval {CI}, 1.45-8.48]; P = .005), brain frontal contusion (OR, 3.22 [95% CI, 1.31-8.49]; P = .01), prehospital or admission arterial hypotension (OR, 4.86 [95% CI, 2.03-12.60]; P = .006), and a Marshall computed tomography (CT) score of 6 (OR, 3.25 [95% CI, 1.31-8.20]; P = .01). The SND score was defined with a range from 0 to 10. The score included the following variables: age >60 years (3 points), prehospital or admission arterial hypotension (3 points), frontal contusion (2 points), and Marshall CT score of 6 (2 points). The score was able to detect patients at risk of SND, with an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI, 0.65-0.82). A score of 3 had a sensitivity of 85%, a specificity of 50%, a VPN of 87%, and a VPP of 44 % to predict SND. CONCLUSIONS: In this study, we demonstrate that moTBI patients have a significant risk of SND. A simple weighted score at hospital admission could be able to detect patients at risk of SND. The use of the score may enable optimization of care resources for these patients.
Assuntos
Lesões Encefálicas Traumáticas , Contusões , Hipotensão , Adulto , Humanos , Pessoa de Meia-Idade , Triagem , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/terapia , Escala de Coma de Glasgow , Estudos RetrospectivosRESUMO
BACKGROUND: The prognostication of long-term functional outcomes remains challenging in patients with traumatic brain injury (TBI). Our aim was to demonstrate that intensive care unit (ICU) variables are not efficient to predict 6-month functional outcome in survivors with moderate to severe TBI (msTBI) but are mostly associated with mortality, which leads to a mortality bias for models predicting a composite outcome of mortality and severe disability. METHODS: We analyzed the data from the multicenter randomized controlled Continuous Hyperosmolar Therapy in Traumatic Brain-Injured Patients trial and developed predictive models using machine learning methods and baseline characteristics and predictors collected during ICU stay. We compared our models' predictions of 6-month binary Glasgow Outcome Scale extended (GOS-E) score in all patients with msTBI (unfavorable GOS-E 1-4 vs. favorable GOS-E 5-8) with mortality (GOS-E 1 vs. GOS-E 2-8) and binary functional outcome in survivors with msTBI (severe disability GOS-E 2-4 vs. moderate to no disability GOS-E 5-8). We investigated the link between ICU variables and long-term functional outcomes in survivors with msTBI using predictive modeling and factor analysis of mixed data and validated our hypotheses on the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. RESULTS: Based on data from 370 patients with msTBI and classically used ICU variables, the prediction of the 6-month outcome in survivors was inefficient (mean area under the receiver operating characteristic 0.52). Using factor analysis of mixed data graph, we demonstrated that high-variance ICU variables were not associated with outcome in survivors with msTBI (p = 0.15 for dimension 1, p = 0.53 for dimension 2) but mostly with mortality (p < 0.001 for dimension 1), leading to a mortality bias for models predicting a composite outcome of mortality and severe disability. We finally identified this mortality bias in the IMPACT model. CONCLUSIONS: We demonstrated using machine learning-based predictive models that classically used ICU variables are strongly associated with mortality but not with 6-month outcome in survivors with msTBI, leading to a mortality bias when predicting a composite outcome of mortality and severe disability.
RESUMO
BACKGROUND: Robust evidence to inform best transfusion management after major oncologic surgery, where postoperative recovery might impact treatment regimens for cancer, is lacking. We conducted a study to validate the feasibility of a larger trial comparing liberal versus restrictive red blood cells (RBC) transfusion strategies after major oncologic surgery. STUDY DESIGN AND METHODS: This was a two-center, randomized, controlled, study of patients admitted to the intensive care unit after major oncologic surgery. Patients whose hemoglobin level dropped below 9.5 g/dL, were randomly assigned to immediately receive a 1-unit RBC transfusion (liberal) or delayed until the hemoglobin level dropped below 7.5 g/dL (restrictive). The primary outcome was the median hemoglobin level between randomization to day 30 post-surgery. Disability-free survival was evaluated by the WHODAS 2.0 questionnaire. RESULTS: 30 patients were randomized (15 patients/group) in 15 months with a mean recruitment rate of 1.8 patients per month. The median hemoglobin level was significantly higher in the liberal group than in the restrictive group: 10.1 g/dL (IQR 9.6-10.5) versus 8.8 g/dL (IQR 8.3-9.4), p < .001, and RBC transfusion rates were 100% versus 66.7%, p = .04. The disability-free survival was similar between groups: 26.7% versus 20%, p = 1. DISCUSSION: Our results support the feasibility of a phase 3 randomized controlled trial comparing the impact of liberal versus restrictive transfusion strategies on the functional recovery of critically ill patients following major oncologic surgery.
Assuntos
Transfusão de Sangue , Hemoglobinas , Humanos , Projetos Piloto , Hemoglobinas/análise , Transfusão de Eritrócitos/métodos , Unidades de Terapia IntensivaRESUMO
BACKGROUND: To evaluate if the increase in chloride intake during a continuous infusion of 20% hypertonic saline solution (HSS) is associated with an increase in the incidence of acute kidney injury (AKI) compared to standard of care in traumatic brain injury patients. METHODS: In this post hoc analysis of the COBI trial, 370 patients admitted for a moderate-to-severe TBI in the 9 participating ICUs were enrolled. The intervention consisted in a continuous infusion of HSS to maintain a blood sodium level between 150 and 155 mmol/L for at least 48 h. Patients enrolled in the control arm were treated as recommended by the latest Brain Trauma foundation guidelines. The primary outcome of this study was the occurrence of AKI within 28 days after enrollment. AKI was defined by stages 2 or 3 according to KDIGO criteria. RESULTS: After exclusion of missing data, 322 patients were included in this post hoc analysis. The patients randomized in the intervention arm received a significantly higher amount of chloride during the first 4 days (intervention group: 97.3 ± 31.6 g vs. control group: 61.3 ± 38.1 g; p < 0.001) and had higher blood chloride levels at day 4 (117.9 ± 10.7 mmol/L vs. 111.6 ± 9 mmol/L, respectively, p < 0.001). The incidence of AKI was not statistically different between the intervention and the control group (24.5% vs. 28.9%, respectively; p = 0.45). CONCLUSIONS: Despite a significant increase in chloride intake, a continuous infusion of HSS was not associated with AKI in moderate-to-severe TBI patients. Our study does not confirm the potentially detrimental effect of chloride load on kidney function in ICU patients. TRIAL REGISTRATION: The COBI trial was registered on clinicaltrial.gov (Trial registration number: NCT03143751, date of registration: 8 May 2017).
Assuntos
Injúria Renal Aguda , Lesões Encefálicas Traumáticas , Humanos , Cloreto de Sódio , Solução Salina , Cloretos , Lesões Encefálicas Traumáticas/complicações , Solução Salina Hipertônica/uso terapêutico , Injúria Renal Aguda/etiologia , RimRESUMO
BACKGROUND: Response to prophylactic platelet transfusion is suspected to be inconsistent in critically ill patients questioning how to optimize transfusion practices. This study aimed to describe prophylactic platelet transfusion response, to identify factors associated with a suboptimal response, to analyse the correlation between corrected count increment and platelet count increment and to determine the association between poor platelet transfusion response and clinical outcomes. METHODS: This prospective multicentre observational study recruited patients who received at least one prophylactic platelet transfusion in one of the nine participating intensive care units for a period up to 16 months. Poor platelet transfusion response was defined as a corrected count increment (CCI) that adjusts for platelet dose and body surface area, less than 7 at 18-24 h after platelet transfusion. Factors associated with poor platelet transfusion response were assessed in a mixed-effect model. Sensitivity analyses were conducted in patients with and without haematology malignancy and chemotherapy. RESULTS: Poor platelet transfusion response occurred in 349 of the 472 (73.9%) prophylactic platelet transfusions and in 141/181 (77.9%) patients. The mixed-effect model identified haemoglobin at ICU admission (odds ratio (OR): 0.79 [95% confidence interval (CI) 0.7-0.89]) and body mass index (BMI) (OR: 0.93 [0.89-0.98]) being positively and independently associated with platelet transfusion response, while a haematological malignancy (OR 1.93 [1.09-3.43]), sepsis as primary ICU admission diagnosis (OR: 2.81 [1.57-5.03]), SOFA score (OR 1.10 [1.03; 1.17]) and maximum storage duration of platelet (OR: 1.24 [1.02-1.52]) were independently associated with a suboptimal platelet increment. Clinical outcomes did not differ between groups, nor the requirement for red blood cells. Poor platelet transfusion response was found in 93.5% of patients with haematology malignancy and chemotherapy. CONCLUSIONS: In this study of critically ill patients, of whom more than half had bone marrow failure, almost three quarters of prophylactic platelet transfusions led to suboptimal platelet increment measured 18 to 24 h following platelet transfusion. Platelet storage duration was the only factor associated with poor platelet response that may be accessible to intervention. Trial registration in October 2017: ClinicalTrials.gov: NCT03325140.
Assuntos
Neoplasias Hematológicas , Trombocitopenia , Humanos , Hemorragia/complicações , Transfusão de Plaquetas , Trombocitopenia/terapia , Estudos Prospectivos , Estado Terminal/terapia , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/complicaçõesRESUMO
BACKGROUND: Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. METHODS: We performed a prospective multicentric study in patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain. RESULTS: Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 [4-12] days (median [interquartile]). At 3 months, the median intensity of pain symptoms was 2 [1-5] in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI [1.1-2.1]), prior use of anti-depressive agents (OR 2.2 95% CI [1.3-4]), prone positioning (OR 3 95% CI [1.4-6.4]) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI [1.7-3.4]) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI [2.1-6]) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months. CONCLUSIONS: Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain. TRIAL REGISTRATION: NCT04817696. Registered March 26, 2021.
Assuntos
Estado Terminal , Neuralgia , Humanos , Feminino , Pessoa de Meia-Idade , Prevalência , Estado Terminal/epidemiologia , Estado Terminal/terapia , Estudos Prospectivos , Cuidados Críticos , Fatores de RiscoRESUMO
Importance: It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent. Objective: To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation. Design, Setting, and Participants: Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021. Interventions: Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 µg/kg; n = 575) immediately after injection of a hypnotic. Main Outcomes and Measures: The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%. Results: Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%). Conclusions and Relevance: Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03960801.
Assuntos
Analgésicos Opioides , Intubação Intratraqueal , Bloqueadores Neuromusculares , Indução e Intubação de Sequência Rápida , Remifentanil , Aspiração Respiratória , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/uso terapêutico , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Bloqueadores Neuromusculares/administração & dosagem , Bloqueadores Neuromusculares/efeitos adversos , Bloqueadores Neuromusculares/uso terapêutico , Indução e Intubação de Sequência Rápida/efeitos adversos , Indução e Intubação de Sequência Rápida/métodos , Remifentanil/administração & dosagem , Remifentanil/efeitos adversos , Remifentanil/uso terapêutico , Aspiração Respiratória/etiologia , Aspiração Respiratória/prevenção & controle , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , IdosoRESUMO
BACKGROUND: It is speculated that the anesthetic strategy during endovascular therapy for stroke may have an impact on the outcome of the patients. The authors hypothesized that conscious sedation is associated with a better functional outcome 3 months after endovascular therapy for the treatment of stroke compared with general anesthesia. METHODS: In this single-blind, randomized trial, patients received either a standardized general anesthesia or a standardized conscious sedation. Blood pressure control was also standardized in both groups. The primary outcome measure was a modified Rankin score less than or equal to 2 (0 = no symptoms; 5 = severe disability) assessed 3 months after treatment. The main secondary outcomes were complications, mortality, reperfusion results, and National Institutes of Health Stroke Scores at days 1 and 7. RESULTS: Of 351 randomized patients, 345 were included in the analysis. The primary outcome occurred in 129 of 341 (38%) of the patients: 63 (36%) in the conscious sedation group and 66 (40%) in the general anesthesia group (relative risk, 0.91 [95% CI, 0.69 to 1.19]; P = 0.474). Patients in the general anesthesia group experienced more intraoperative hypo- or hypertensive episodes, while the cumulative duration was not different (mean ± SD, 36 ± 31 vs. 39 ± 25 min; P = 0.079). The time from onset and from arrival to puncture were longer in the general anesthesia group (mean difference, 19 min [i.e., -00:19] [95% CI, -0:38 to 0] and mean difference, 9 min [95% CI, -0:18 to -0:01], respectively), while the time from onset to recanalization was similar in both groups. Recanalization was more often successful in the general anesthesia group (144 of 169 [85%] vs. 131 of 174 [75%]; P = 0.021). The incidence of symptomatic intracranial hemorrhage was similar in both groups. CONCLUSIONS: The functional outcomes 3 months after endovascular treatment for stroke were similar with general anesthesia and sedation. Our results, therefore, suggest that clinicians can use either approach.
Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Anestesia Geral/efeitos adversos , Pressão Sanguínea , Sedação Consciente/métodos , Procedimentos Endovasculares/efeitos adversos , Humanos , Método Simples-Cego , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Trombectomia/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes. METHODS: Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low: < 10 kcal/kg, < 0.8 g/kg; moderate: 10-20 kcal/kg, 0.8-1.2 g/kg, high: > 20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV). RESULTS: A total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (- 2.74 [- 3.28; - 2.21] and - 0.12 [- 0.15; - 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements. CONCLUSIONS: Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes. Trial registration NCT04143503 , registered on October 25, 2019.
Assuntos
Estado Terminal , Nutrição Parenteral , Adulto , Estudos de Coortes , Estado Terminal/terapia , Ingestão de Energia , Humanos , Unidades de Terapia Intensiva , Estudos ProspectivosRESUMO
INTRODUCTION: Brain multimodal monitoring including intracranial pressure (ICP) and brain tissue oxygen pressure (PbtO2) is more accurate than ICP alone in detecting cerebral hypoperfusion after traumatic brain injury (TBI). No data are available for the predictive role of a dynamic hyperoxia test in brain-injured patients from diverse etiology. AIM: To examine the accuracy of ICP, PbtO2 and the oxygen ratio (OxR) in detecting regional cerebral hypoperfusion, assessed using perfusion cerebral computed tomography (CTP) in patients with acute brain injury. METHODS: Single-center study including patients with TBI, subarachnoid hemorrhage (SAH) and intracranial hemorrhage (ICH) undergoing cerebral blood flow (CBF) measurements using CTP, concomitantly to ICP and PbtO2 monitoring. Before CTP, FiO2 was increased directly from baseline to 100% for a period of 20 min under stable conditions to test the PbtO2 catheter, as a standard of care. Cerebral monitoring data were recorded and samples were taken, allowing the measurement of arterial oxygen pressure (PaO2) and PbtO2 at FiO2 100% as well as calculation of OxR (= ΔPbtO2/ΔPaO2). Regional CBF (rCBF) was measured using CTP in the tissue area around intracranial monitoring by an independent radiologist, who was blind to the PbtO2 values. The accuracy of different monitoring tools to predict cerebral hypoperfusion (i.e., CBF < 35 mL/100 g × min) was assessed using area under the receiver-operating characteristic curves (AUCs). RESULTS: Eighty-seven CTPs were performed in 53 patients (median age 52 [41-63] years-TBI, n = 17; SAH, n = 29; ICH, n = 7). Cerebral hypoperfusion was observed in 56 (64%) CTPs: ICP, PbtO2 and OxR were significantly different between CTP with and without hypoperfusion. Also, rCBF was correlated with ICP (r = - 0.27; p = 0.01), PbtO2 (r = 0.36; p < 0.01) and OxR (r = 0.57; p < 0.01). Compared with ICP alone (AUC = 0.65 [95% CI, 0.53-0.76]), monitoring ICP + PbO2 (AUC = 0.78 [0.68-0.87]) or ICP + PbtO2 + OxR (AUC = 0.80 (0.70-0.91) was significantly more accurate in predicting cerebral hypoperfusion. The accuracy was not significantly different among different etiologies of brain injury. CONCLUSIONS: The combination of ICP and PbtO2 monitoring provides a better detection of cerebral hypoperfusion than ICP alone in patients with acute brain injury. The use of dynamic hyperoxia test could not significantly increase the diagnostic accuracy.
Assuntos
Lesões Encefálicas Traumáticas , Hiperóxia , Encéfalo/diagnóstico por imagem , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Circulação Cerebrovascular , Humanos , Pressão Intracraniana , Pessoa de Meia-Idade , OxigênioRESUMO
BACKGROUND: Anaemia is common prior to cardiac surgery and contributes to perioperative morbidity. Iron deficiency is the main cause of anaemia but its impact remains controversial in the surgical setting. We aimed to estimate the impact of iron deficiency on in-hospital perioperative red blood cell transfusion for patients undergoing elective and urgent cardiac surgery. Secondary objectives were to identify risk factors associated with in-hospital red blood cell transfusion. METHODS: We conducted a prospective multicentre observational study in three university hospitals performing cardiac surgery. We determined iron status prior to surgery and collected all transfusion data to compare iron-deficient and iron-replete patients during hospital stay. We performed a multivariable logistic regression to compare transfusion among groups. RESULTS: Five hundred and two patients were included. A trend of low haemoglobin levels associated with iron deficiency persisted until discharge. Red blood cell transfusion was significantly higher in the group of iron deficient patients during surgery (22% vs 13%, p = 0.017), however the incidence during the whole hospital stay was 31% in the iron-deficient group, not significantly different with the non-deficient group (26%, p = 0.28). Iron deficiency was not independently associated with in-hospital red blood cell transfusion (adjusted OR = 0.85 [0.53-1.36], p = 0.49). CONCLUSIONS: In-hospital red blood cell transfusion was not significantly higher in iron-deficient patients and iron deficiency was not associated with in-hospital red blood cell transfusion in patients undergoing elective and urgent cardiac surgery. Iron deficiency was the main cause of anaemia and anaemia was a strong driver of red blood cell transfusion. Further studies should identify sub-population of iron-deficient patients which may benefit from preoperative iron deficiency management and explore the long-term impact of lower haemoglobin levels at discharge in the iron deficient population.
Assuntos
Anemia Ferropriva , Anemia , Procedimentos Cirúrgicos Cardíacos , Deficiências de Ferro , Anemia/complicações , Anemia/epidemiologia , Anemia/terapia , Anemia Ferropriva/complicações , Anemia Ferropriva/epidemiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Transfusão de Eritrócitos/efeitos adversos , Hemoglobinas/análise , Humanos , Ferro , Estudos ProspectivosRESUMO
OBJECTIVES: Mannitol and hypertonic saline are used to treat raised intracerebral pressure in patients with traumatic brain injury, but their possible effects on kidney function and mortality are unknown. DESIGN: A post hoc analysis of the erythropoietin trial in traumatic brain injury (ClinicalTrials.gov NCT00987454) including daily data on mannitol and hypertonic saline use. SETTING: Twenty-nine university-affiliated teaching hospitals in seven countries. PATIENTS: A total of 568 patients treated in the ICU for 48 hours without acute kidney injury of whom 43 (7%) received mannitol and 170 (29%) hypertonic saline. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We categorized acute kidney injury stage according to the Kidney Disease Improving Global Outcome classification and defined acute kidney injury as any Kidney Disease Improving Global Outcome stage-based changes from the admission creatinine. We tested associations between early (first 2 d) mannitol and hypertonic saline and time to acute kidney injury up to ICU discharge and death up to 180 days with Cox regression analysis. Subsequently, acute kidney injury developed more often in patients receiving mannitol (35% vs 10%; p < 0.001) and hypertonic saline (23% vs 10%; p < 0.001). On competing risk analysis including factors associated with acute kidney injury, mannitol (hazard ratio, 2.3; 95% CI, 1.2-4.3; p = 0.01), but not hypertonic saline (hazard ratio, 1.6; 95% CI, 0.9-2.8; p = 0.08), was independently associated with time to acute kidney injury. In a Cox model for predicting time to death, both the use of mannitol (hazard ratio, 2.1; 95% CI, 1.1-4.1; p = 0.03) and hypertonic saline (hazard ratio, 1.8; 95% CI, 1.02-3.2; p = 0.04) were associated with time to death. CONCLUSIONS: In this post hoc analysis of a randomized controlled trial, the early use of mannitol, but not hypertonic saline, was independently associated with an increase in acute kidney injury. Our findings suggest the need to further evaluate the use and choice of osmotherapy in traumatic brain injury.
Assuntos
Injúria Renal Aguda/metabolismo , Lesões Encefálicas Traumáticas/terapia , Diuréticos Osmóticos/uso terapêutico , Eritropoetina/metabolismo , Manitol/uso terapêutico , Solução Salina Hipertônica/uso terapêutico , Injúria Renal Aguda/etiologia , Lesões Encefálicas Traumáticas/tratamento farmacológico , Diuréticos Osmóticos/efeitos adversos , Feminino , Hidratação/métodos , Humanos , Pressão Intracraniana/efeitos dos fármacos , Masculino , Manitol/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Equipoise remains on the optimal transfusion strategy in surgical oncologic patients. The primary objective of our study was to determine the impact of anaemia and red blood cells (RBCs) transfusion on severe postoperative complications in surgical oncologic critically ill patients. MATERIALS AND METHODS: Retrospective single-centre study. Adults admitted to intensive care unit after major oncologic surgery were eligible. Analyses to determine the independent risk factors, including anaemia or RBC transfusion, for postoperative complications and/or hospital mortality were performed. RESULTS: Of the 283 patients included, 246 patients (86.9%) had anaemia. Fifty-five patients (19·4%) were transfused. Patients exposed to moderate-to-severe anaemia or RBC transfusion had more often severe complications, especially acute kidney injury and infectious complications. Multivariate analysis found an independent association between moderate and severe anaemia and severe postoperative complications (moderate anaemia: OR 14·02 [2·52-264]; severe anaemia: OR 16·25 [2·62-318·5]; P < 0·05). Elderly, obese patients and patients operated from abdominal surgery appeared to be more vulnerable to anaemia than other patients. Transfusion was also an independent risk factor for postoperative complications (OR 4·19 [2·12-8·39]; P < 0·001). When considering moderate-to-severe anaemic patients, RBC transfusion was no longer associated with postoperative complications. CONCLUSIONS: Anaemia was associated with severe postoperative complications, and this association was stronger in elderly, obese patients and after abdominal surgery. RBC transfusion also negatively impacts on patients' prognosis. However, this association was not found in case of moderate-to-severe anaemia exposure (haemoglobin < 10 g/dl).
Assuntos
Anemia , Transfusão de Eritrócitos , Idoso , Anemia/terapia , Estado Terminal , Transfusão de Eritrócitos/efeitos adversos , Hemoglobinas/análise , Humanos , Estudos RetrospectivosRESUMO
Importance: Fluid therapy is an important component of care for patients with traumatic brain injury, but whether it modulates clinical outcomes remains unclear. Objective: To determine whether continuous infusion of hypertonic saline solution improves neurological outcome at 6 months in patients with traumatic brain injury. Design, Setting, and Participants: Multicenter randomized clinical trial conducted in 9 intensive care units in France, including 370 patients with moderate to severe traumatic brain injury who were recruited from October 2017 to August 2019. Follow-up was completed in February 2020. Interventions: Adult patients with moderate to severe traumatic brain injury were randomly assigned to receive continuous infusion of 20% hypertonic saline solution plus standard care (n = 185) or standard care alone (controls; n = 185). The 20% hypertonic saline solution was administered for 48 hours or longer if patients remained at risk of intracranial hypertension. Main Outcomes and Measures: The primary outcome was Extended Glasgow Outcome Scale (GOS-E) score (range, 1-8, with lower scores indicating worse functional outcome) at 6 months, obtained centrally by blinded assessors and analyzed with ordinal logistic regression adjusted for prespecified prognostic factors (with a common odds ratio [OR] >1.0 favoring intervention). There were 12 secondary outcomes measured at multiple time points, including development of intracranial hypertension and 6-month mortality. Results: Among 370 patients who were randomized (median age, 44 [interquartile range, 27-59] years; 77 [20.2%] women), 359 (97%) completed the trial. The adjusted common OR for the GOS-E score at 6 months was 1.02 (95% CI, 0.71-1.47; P = .92). Of the 12 secondary outcomes, 10 were not significantly different. Intracranial hypertension developed in 62 (33.7%) patients in the intervention group and 66 (36.3%) patients in the control group (absolute difference, -2.6% [95% CI, -12.3% to 7.2%]; OR, 0.80 [95% CI, 0.51-1.26]). There was no significant difference in 6-month mortality (29 [15.9%] in the intervention group vs 37 [20.8%] in the control group; absolute difference, -4.9% [95% CI, -12.8% to 3.1%]; hazard ratio, 0.79 [95% CI, 0.48-1.28]). Conclusions and Relevance: Among patients with moderate to severe traumatic brain injury, treatment with continuous infusion of 20% hypertonic saline compared with standard care did not result in a significantly better neurological status at 6 months. However, confidence intervals for the findings were wide, and the study may have had limited power to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03143751.
Assuntos
Lesões Encefálicas Traumáticas/terapia , Hidratação , Solução Salina Hipertônica/uso terapêutico , Adulto , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Terapia Combinada , Feminino , Escala de Resultado de Glasgow , Humanos , Hipernatremia/etiologia , Hipnóticos e Sedativos/uso terapêutico , Infusões Intravenosas , Hipertensão Intracraniana/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Solução Salina Hipertônica/administração & dosagem , Solução Salina Hipertônica/efeitos adversosRESUMO
BACKGROUND: Hypophosphataemia affects up to one-third of patients in the intensive care unit (ICU) and is particularly common during sepsis. Experimental data suggest that hypophosphataemia leads to an acquired dysfunction of leukocytes, thus promoting infections and increasing the risk of death during sepsis. OBJECTIVES: The aim of our study was to investigate the association between hypophosphataemia and mortality in critically ill patients with a bloodstream infection (BSI). METHODS: We performed a retrospective study in three ICUs during an 18-month period. All adults with a BSI diagnosed in the ICU were eligible. Patients with and without hypophosphataemia, defined as phosphataemia below 0.8 mmol/L, were compared. A multivariate survival analysis using a Cox proportional hazard regression model was conducted to study the association between hypophosphataemia and 90-d mortality. RESULTS/FINDINGS: Among the 3783 patients admitted to the three participating ICUs within the 18-month study period, 203 met the inclusion criteria and 193 were analysed. Fifty-four patients had hypophosphataemia. After adjusting for confounders, hypophosphataemia was significantly associated with a twofold increased risk of 90-d mortality (hazard ratio = 2.10 [1.177-3.80], p = 0.013). This association is particularly strong in patients without shock. CONCLUSIONS: Hypophosphataemia was independently associated with a twofold increase in 90-d mortality in ICU patients with a BSI. These results suggest that investigators and physicians should include phosphataemia as a predictor of the severity of BSIs. Further research is warranted to better understand this association and to determine the potential benefits of systematic monitoring of phosphataemia and phosphorus supplementation. CLINICAL TRIAL REGISTRATION: NCT03529058.
Assuntos
Hipofosfatemia , Sepse , Adulto , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Estudos RetrospectivosRESUMO
Importance: It is not known if use of colloid solutions containing hydroxyethyl starch (HES) to correct for intravascular deficits in high-risk surgical patients is either effective or safe. Objective: To evaluate the effect of HES 130/0.4 compared with 0.9% saline for intravascular volume expansion on mortality and postoperative complications after major abdominal surgery. Design, Setting, and Participants: Multicenter, double-blind, parallel-group, randomized clinical trial of 775 adult patients at increased risk of postoperative kidney injury undergoing major abdominal surgery at 20 university hospitals in France from February 2016 to July 2018; final follow-up was in October 2018. Interventions: Patients were randomized to receive fluid containing either 6% HES 130/0.4 diluted in 0.9% saline (n = 389) or 0.9% saline alone (n = 386) in 250-mL boluses using an individualized hemodynamic algorithm during surgery and for up to 24 hours on the first postoperative day, defined as ending at 7:59 am the following day. Main Outcomes and Measures: The primary outcome was a composite of death or major postoperative complications at 14 days after surgery. Secondary outcomes included predefined postoperative complications within 14 days after surgery, durations of intensive care unit and hospital stays, and all-cause mortality at postoperative days 28 and 90. Results: Among 826 patients enrolled (mean age, 68 [SD, 7] years; 91 women [12%]), 775 (94%) completed the trial. The primary outcome occurred in 139 of 389 patients (36%) in the HES group and 125 of 386 patients (32%) in the saline group (difference, 3.3% [95% CI, -3.3% to 10.0%]; relative risk, 1.10 [95% CI, 0.91-1.34]; P = .33). Among 12 prespecified secondary outcomes reported, 11 showed no significant difference, but a statistically significant difference was found in median volume of study fluid administered on day 1: 1250 mL (interquartile range, 750-2000 mL) in the HES group and 1500 mL (interquartile range, 750-2150 mL) in the saline group (median difference, 250 mL [95% CI, 83-417 mL]; P = .006). At 28 days after surgery, 4.1% and 2.3% of patients had died in the HES and saline groups, respectively (difference, 1.8% [95% CI, -0.7% to 4.3%]; relative risk, 1.76 [95% CI, 0.79-3.94]; P = .17). Conclusions and Relevance: Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery. These findings do not support the use of HES for volume replacement therapy in such patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02502773.
Assuntos
Abdome/cirurgia , Hidratação/métodos , Derivados de Hidroxietil Amido/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Solução Salina/uso terapêutico , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Injúria Renal Aguda/prevenção & controle , Idoso , Método Duplo-Cego , Feminino , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estatísticas não ParamétricasAssuntos
Trombocitopenia , Trombose , Vacinas , Heparina , Humanos , Imunoensaio , Trombocitopenia/induzido quimicamenteRESUMO
BACKGROUND: Acute kidney injury (AKI) in traumatic brain injury (TBI) is poorly understood and it is unknown if it can be attenuated using erythropoietin (EPO). METHODS: Pre-planned analysis of patients included in the EPO-TBI (ClinicalTrials.gov NCT00987454) trial who were randomized to weekly EPO (40 000 units) or placebo (0.9% sodium chloride) subcutaneously up to three doses or until intensive care unit (ICU) discharge. Creatinine levels and urinary output (up to 7 days) were categorized according to the Kidney Disease Improving Global Outcome (KDIGO) classification. Severity of TBI was categorized with the International Mission for Prognosis and Analysis of Clinical Trials in TBI. RESULTS: Of 3348 screened patients, 606 were randomized and 603 were analyzed. Of these, 82 (14%) patients developed AKI according to KDIGO (60 [10%] with KDIGO 1, 11 [2%] patients with KDIGO 2, and 11 [2%] patients with KDIGO 3). Male gender (hazard ratio [HR] 4.0 95% confidence interval [CI] 1.4-11.2, P = 0.008) and severity of TBI (HR 1.3 95% CI 1.1-1.4, P < 0.001 for each 10% increase in risk of poor 6 month outcome) predicted time to AKI. KDIGO stage 1 (HR 8.8 95% CI 4.5-17, P < 0.001), KDIGO stage 2 (HR 13.2 95% CI 3.9-45.2, P < 0.001) and KDIGO stage 3 (HR 11.7 95% CI 3.5-39.7, P < 0.005) predicted time to mortality. EPO did not influence time to AKI (HR 1.08 95% CI 0.7-1.67, P = 0.73) or creatinine levels during ICU stay (P = 0.09). CONCLUSIONS: Acute kidney injury is more common in male patients and those with severe compared to moderate TBI and appears associated with worse outcome. EPO does not prevent AKI after TBI.