RESUMEN
BACKGROUND: Acute respiratory distress syndrome (ARDS) is responsible for 400,000 deaths annually worldwide. Few improvements have been made despite five decades of research, partially because ARDS is a highly heterogeneous syndrome including various types of aetiologies. Lower airway microbiota is involved in chronic inflammatory diseases and recent data suggest that it could also play a role in ARDS. Nevertheless, whether the lower airway microbiota composition varies between the aetiologies of ARDS remain unknown. The aim of this study is to compare lower airway microbiota composition between ARDS aetiologies, i.e. pulmonary ARDS due to influenza, SARS-CoV-2 or bacterial infection. METHODS: Consecutive ARDS patients according to Berlin's classification requiring invasive ventilation with PCR-confirmed influenza or SARS-CoV-2 infections and bacterial infections (> 105 CFU/mL on endotracheal aspirate) were included. Endotracheal aspirate was collected at admission, V3-V4 and ITS2 regions amplified by PCR, deep-sequencing performed on MiSeq sequencer (Illumina®) and data analysed using DADA2 pipeline. RESULTS: Fifty-three patients were included, 24 COVID-19, 18 influenza, and 11 bacterial CAP-related ARDS. The lower airway bacteriobiota and mycobiota compositions (ß-diversity) were dissimilar between the three groups (p = 0.05 and p = 0.01, respectively). The bacterial α-diversity was significantly lower in the bacterial CAP-related ARDS group compared to the COVID-19 ARDS group (p = 0.04). In contrast, influenza-related ARDS patients had higher lung mycobiota α-diversity than the COVID-19-related ARDS (p = 0 < 01). CONCLUSION: Composition of lower airway microbiota (both microbiota and mycobiota) differs between influenza, COVID-19 and bacterial CAP-related ARDS. Future studies investigating the role of lung microbiota in ARDS pathophysiology should take aetiology into account.
Asunto(s)
COVID-19 , Gripe Humana , Microbiota , Síndrome de Dificultad Respiratoria , Humanos , COVID-19/microbiología , COVID-19/complicaciones , COVID-19/fisiopatología , Síndrome de Dificultad Respiratoria/microbiología , Síndrome de Dificultad Respiratoria/virología , Síndrome de Dificultad Respiratoria/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Gripe Humana/microbiología , Gripe Humana/fisiopatología , Gripe Humana/complicaciones , Microbiota/fisiología , Anciano , Infecciones Bacterianas/microbiologíaRESUMEN
BACKGROUND: The benefit-risk ratio of prophylactic non-invasive ventilation (NIV) and high-flow nasal oxygen therapy (HFNC-O2) during the early stage of blunt chest trauma remains controversial because of limited data. The main objective of this study was to compare the rate of endotracheal intubation between two NIV strategies in high-risk blunt chest trauma patients. METHODS: The OptiTHO trial was a randomized, open-label, multicenter trial over a two-year period. Every adult patients admitted in intensive care unit within 48 h after a high-risk blunt chest trauma (Thoracic Trauma Severity Score ≥ 8), an estimated PaO2/FiO2 ratio < 300 and no evidence of acute respiratory failure were eligible for study enrollment (Clinical Trial Registration: NCT03943914). The primary objective was to compare the rate of endotracheal intubation for delayed respiratory failure between two NIV strategies: i) a prompt association of HFNC-O2 and "early" NIV in every patient for at least 48 h with vs. ii) the standard of care associating COT and "late" NIV, indicated in patients with respiratory deterioration and/or PaO2/FiO2 ratio ≤ 200 mmHg. Secondary outcomes were the occurrence of chest trauma-related complications (pulmonary infection, delayed hemothorax or moderate-to-severe ARDS). RESULTS: Study enrollment was stopped for futility after a 2-year study period and randomization of 141 patients. Overall, 11 patients (7.8%) required endotracheal intubation for delayed respiratory failure. The rate of endotracheal intubation was not significantly lower in patients treated with the experimental strategy (7% [5/71]) when compared to the control group (8.6% [6/70]), with an adjusted OR = 0.72 (95%IC: 0.20-2.43), p = 0.60. The occurrence of pulmonary infection, delayed hemothorax or delayed ARDS was not significantly lower in patients treated by the experimental strategy (adjusted OR = 1.99 [95%IC: 0.73-5.89], p = 0.18, 0.85 [95%IC: 0.33-2.20], p = 0.74 and 2.14 [95%IC: 0.36-20.77], p = 0.41, respectively). CONCLUSION: A prompt association of HFNC-O2 with preventive NIV did not reduce the rate of endotracheal intubation or secondary respiratory complications when compared to COT and late NIV in high-risk blunt chest trauma patients with non-severe hypoxemia and no sign of acute respiratory failure. CLINICAL TRIAL REGISTRATION: NCT03943914, Registered 7 May 2019.
Asunto(s)
Ventilación no Invasiva , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Traumatismos Torácicos , Heridas no Penetrantes , Adulto , Humanos , Oxígeno/uso terapéutico , Ventilación no Invasiva/efectos adversos , Hemotórax/complicaciones , Traumatismos Torácicos/complicaciones , Traumatismos Torácicos/terapia , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/terapia , Terapia por Inhalación de Oxígeno/efectos adversos , Insuficiencia Respiratoria/terapia , Síndrome de Dificultad Respiratoria/terapia , Intubación Intratraqueal/efectos adversos , Cánula/efectos adversosRESUMEN
The main objective of this pilot study was to determine the association between augmented renal clearance (ARC), urinary nitrogen loss and muscle wasting in critically ill trauma patients. We conducted a retrospective analysis of a local database in 162 critically ill trauma patients without chronic renal dysfunction. Nutritional-related parameters and 24 h urinary biochemical analyses were prospectively collected and averaged over the first ten days after admission. Augmented renal clearance was defined by a mean creatinine clearance (CLCR) > 130 mL/min/1.73 m2. The main outcome was the cumulated nitrogen balance at day 10. The secondary outcome was the variation of muscle psoas cross-sectional area (ΔCSA) calculated in the subgroup of patients who underwent at least two abdominal CT scans during the ICU length of stay. Overall, there was a significant correlation between mean CLCR and mean urinary nitrogen loss (normalized coefficient: 0.47 ± 0.07, p < 0.0001). ARC was associated with a significantly higher urinary nitrogen loss (17 ± 5 vs. 14 ± 4 g/day, p < 0.0001) and a lower nitrogen balance (-6 ± 5 vs. -4 ± 5 g/day, p = 0.0002), without difference regarding the mean protein intake (0.7 ± 0.2 vs. 0.7 ± 0.3 g/kg/day, p = 0.260). In the subgroup of patients who underwent a second abdominal CT scan (N = 47), both ΔCSA and %ΔCSA were higher in ARC patients (-33 [-41; -25] vs. -15 [-29; -5] mm2/day, p = 0.010 and -3 [-3; -2] vs. -1 [-3; -1] %/day, p = 0.008). Critically ill trauma patients with ARC are thus characterized by a lower nitrogen balance and increased muscle loss over the 10 first days after ICU admission. The interest of an increased protein intake (>1.5 g/kg/day) in such patients remains a matter of controversy and must be confirmed by further randomized trials.
Asunto(s)
Creatinina/orina , Enfermedad Crítica/terapia , Nitrógeno/orina , Músculos Psoas/metabolismo , Eliminación Renal , Adulto , Bases de Datos Factuales , Femenino , Humanos , Unidades de Cuidados Intensivos , Riñón/fisiopatología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Apoyo Nutricional , Proyectos Piloto , Estudios Prospectivos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The main objective was to assess the performance of the neutrophil-lymphocyte ratio (NLR) for early prediction of delayed neurological impairment and cerebral contusion worsening in patients with mild-to-moderate traumatic brain injury (TBI). METHODS: Over a 3-year period, every adult patient triaged to our level 1 trauma center with brain contusion and Glasgow Coma Scale (GCS) of 10 or greater were retrospectively included. The main study outcome was the occurrence of delayed clinical deterioration, defined as a GCS < 10 and/or a secondary need for mechanical ventilation, within 5 days after TBI. The performance of NLR for prediction of delayed clinical deterioration was assessed by receiver operating characteristic (ROC) curve. RESULTS: Overall, 115 patients were included and 16 (14%) presented a delayed clinical deterioration. Overall, the NLR at ED admission was higher in patients who developed a delayed clinical deterioration (18 [12-29] vs 8 [5-13], p = 0.0003). The area under the ROC curves for NLR at ED admission in predicting delayed clinical deterioration was 0.79 [0.65-0.93] and NLR > 15 was found to be independently associated with the occurrence of delayed clinical deterioration (adjusted OR = 10.1 [95%CI: 2.3-45.6]). CONCLUSION: The NLR at ED admission was independently associated with the occurrence of delayed clinical deterioration, although limited by a poor discriminative value by itself. Further studies are needed to test the predictive value of composite scoring systems including NLR for prevention of under-triage of patients with mild-to-moderate TBI.
Asunto(s)
Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/fisiopatología , Deterioro Clínico , Linfocitos/citología , Neutrófilos/citología , Adulto , Anciano , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Respiración Artificial , Estudios Retrospectivos , TriajeRESUMEN
INTRODUCTION: In blunt chest trauma patients, the activation of inflammatory response is thought to be one of the pathophysiological pathways leading to delayed acute respiratory distress syndrome(ARDS). The main objective of the study was to assess the performance of the neutrophil-lymphocyte ratio(NLR) for prediction of delayed ARDS. The secondary objective was to compare NLR in patients with traumarelated focal and non-focal ARDS. METHODS: Over a 2-year period, every adult patient triaged to our level 1 trauma center with multiple rib fractures and PaO 2 /FiO 2 ratio > 200 at admission were retrospectively included. The NLR was recorded at admission in the Emergency Department(ED). The main study outcome was the occurrence of moderate to severe ARDS within 5 days after admission according to Berlin criteria. Two phenotypes (focal and non-focal ARDS) were determined based on the closest chest CT regarding the ARDS onset. RESULTS: 216 patients were included and 42(19%) underwent moderate to severe ARDS within 5 days after ED admission (focal, N = 26 [12%] and non-focal, N = 16 [7%]). The NLR at ED admission was not statistically different between patients who developed or not a delayed ARDS (14 ± 13 vs. 11 ± 8,p = 0.095), although patients with non-focal ARDS presented higher NLR ratio than focal ARDS (21 ± 18 p < 0.0001). The AUC for NLR at ED in predicting delayed ARDS was 0.53. CONCLUSION: In blunt chest trauma patients, the NLR at ED admission was unable to predict delayed ARDS over the five first days post-injury. Although not clinically relevant, the NLR was higher in patients with non focal ARDS.
Asunto(s)
Reglas de Decisión Clínica , Linfocitos/metabolismo , Neutrófilos/metabolismo , Síndrome de Dificultad Respiratoria/diagnóstico , Fracturas de las Costillas/complicaciones , Traumatismos Torácicos/complicaciones , Heridas no Penetrantes/complicaciones , Adulto , Anciano , Biomarcadores/sangre , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Admisión del Paciente , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/etiología , Estudios Retrospectivos , Fracturas de las Costillas/inmunología , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Traumatismos Torácicos/inmunología , Heridas no Penetrantes/inmunologíaRESUMEN
PURPOSE: To assess the impact of delayed hemothorax on outcomes in blunt chest trauma patients without life-threatening condition at admission and characterize the predictive value of predefined anatomical factors for delayed hemothorax. METHODS: In a single-centre retrospective study, every spontaneous breathing patient admitted for a blunt chest trauma without significant pleural effusion at ICU admission was included. A multivariable regression model was used to determine the covariate-adjusted odd of secondary respiratory complications in patients with delayed hemothorax ≥ 500 ml. The characteristics of rib fractures (number, location and displacement) were integrated into a logistic regression model to determine variables associated with delayed hemothorax in multivariate analysis. RESULTS: Over the study period, 109 patients were included and the rate of delayed hemothorax ≥ 500 ml was 36%. Patients with delayed hemothorax had higher rates of pulmonary infections (OR 4.8 [1.6-16.4]) but no statistical association between delayed hemothorax and secondary respiratory failure (OR 2.0 [0.4-9.4]). A posterior location and a displaced rib fracture were independent predictors of delayed hemothorax (OR 3.4 [1.3-8.6] and OR 2.3 [1.1-5.1], respectively). At least one displaced rib fracture was more specific of delayed hemothorax than the commonly used threshold of three or more rib fractures (81.3 vs. 51.5%). CONCLUSION: Delayed hemothorax is a frequent complication associated with increased risk of pulmonary infection. The posterior location and the displacement of at least one rib fracture in the initial CT scan were independent risk factors for predicting the occurrence of delayed hemothorax.
Asunto(s)
Hemotórax/diagnóstico por imagen , Hemotórax/etiología , Tomografía Computarizada por Rayos X/métodos , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Fracturas de las Costillas/complicaciones , Fracturas de las Costillas/diagnóstico por imagen , Factores de RiesgoRESUMEN
BACKGROUND: We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). METHODS: This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. RESULTS: Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38-56%) in the intervention group and 42% (IQR, 25-53%) in the control group (Pâ =â .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (Pâ =â .07) and by 2.8 days in the control period (Pâ =â .02). The durations of ICU stay were 7 days (IQR, 5-14 days) in the control group and 9 days (IQR, 5-20 days) in the intervention group (Pâ =â .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69-2.01; Pâ =â .10). CONCLUSIONS: The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. CLINICAL TRIALS REGISTRATION: NCT03348579.
Asunto(s)
Neumonía Asociada a la Atención Médica , Unidades de Cuidados Intensivos , Adulto , Cuidados Críticos , Hospitales , Humanos , Tiempo de InternaciónRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported. METHODS: Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated. RESULTS: Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12-23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54-140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively. CONCLUSION: Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria.
RESUMEN
BACKGROUND: To explore the underlying mechanisms leading to the occurrence of hyponatremia and enhanced urinary sodium excretion in brain trauma patients using sodium balance and urinary biochemical analysis. METHODS: We conducted a retrospective analysis of a local database prospectively collected in 60 brain trauma patients without chronic renal dysfunction. Metabolic and hemodynamic parameters were averaged over three consecutive periods over the first seven days after admission. The main outcome investigated in this study was the occurrence of at least one episode of hyponatremia. RESULTS: Over the study period, there was a prompt decrease in sodium balance (163 ± 193 vs. -12 ± 154 mmol/day, p < 0.0001) and free water clearance (- 0.7 ± 0.7 vs. -1.8 ± 2.3 ml/min, p < 0.0001). The area under the ROC curves for sodium balance in predicting the occurrence of hyponatremia during the next period was 0.81 [95% CI: 0.64-0.97]. Variables associated with averaged urinary sodium excretion were sodium intake (R2 = 0.26, p < 0.0001) and fractional excretion of urate (R2 = 0.15, p = 0.009). Urinary sodium excretion was also higher in patients with sustained augmented renal clearance over the study period (318 ± 106 vs. 255 ± 135 mmol/day, p = 0.034). CONCLUSION: The decreased vascular volume resulting from a negative sodium balance is a major precipitating factor of hyponatremia in brain trauma patients. Predisposing factors for enhanced urinary sodium excretion were high sodium intake, high fractional excretion of urate and augmented renal clearance over the first seven days after ICU admission.
Asunto(s)
Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/fisiopatología , Hiponatremia/etiología , Hiponatremia/fisiopatología , Sodio/metabolismo , Adulto , Femenino , Humanos , Masculino , Estudios Retrospectivos , SíndromeRESUMEN
The aim was to assess the appropriateness of recommended regimens for empirical MIC coverage in critically ill patients with open-abdomen and negative-pressure therapy (OA/NPT). Over a 5-year period, every critically ill patient who received amikacin and who underwent therapeutic drug monitoring (TDM) while being treated by OA/NPT was retrospectively included. A population pharmacokinetic (PK) modeling was performed considering the effect of 10 covariates (age, sex, total body weight [TBW], adapted body weight [ABW], body surface area [BSA], modified sepsis-related organ failure assessment [SOFA] score, vasopressor use, creatinine clearance [CLCR], fluid balance, and amount of fluids collected by the NPT over the sampling day) in patients who underwent continuous renal replacement therapy (CRRT) or did not receive CRRT. Monte Carlo simulations were employed to determine the fractional target attainment (FTA) for the PK/pharmacodynamic [PD] targets (maximum concentration of drug [Cmax]/MIC ratio of ≥8 and a ratio of the area under the concentration-time curve from 0 to 24 h [AUC0-24]/MIC of ≥75). Seventy critically ill patients treated by OA/NPT (contributing 179 concentration values) were included. Amikacin PK concentrations were best described by a two-compartment model with linear elimination and proportional residual error, with CLCR and ABW as significant covariates for volume of distribution (V) and CLCR for CL. The reported V) in non-CRRT and CRRT patients was 35.8 and 40.2 liters, respectively. In Monte Carlo simulations, ABW-adjusted doses between 25 and 35 mg/kg were needed to reach an FTA of >85% for various renal functions. Despite an increased V and a wide interindividual variability, desirable PK/PD targets may be achieved using an ABW-based loading dose of 25 to 30 mg/kg. When less susceptible pathogens are targeted, higher dosing regimens are probably needed in patients with augmented renal clearance (ARC). Further studies are needed to assess the effect of OA/NPT on the PK parameters of antimicrobial agents.
Asunto(s)
Amicacina/farmacocinética , Antibacterianos/farmacocinética , Hipertensión Intraabdominal/prevención & control , Terapia de Presión Negativa para Heridas/métodos , Técnicas de Abdomen Abierto/efectos adversos , Sepsis/prevención & control , Anciano , Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Enfermedad Crítica/terapia , Femenino , Humanos , Hipertensión Intraabdominal/terapia , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Método de Montecarlo , Técnicas de Abdomen Abierto/métodos , Sepsis/tratamiento farmacológico , Heridas y Lesiones/terapiaRESUMEN
PURPOSE: To compare the rate of therapeutic failure in critically ill patients treated by third-generation cephalosporins (3GCs) or piperacillin-tazobactam (PTZ) for wild-type AmpC-producing Enterobacterales pulmonary infections. METHODS: Over a 4-year period, all adult patients treated for a wild-type AmpC-producing Enterobacterales pulmonary infection were retrospectively included. Two groups of patients were compared according to the definitive antibiotic therapy (3GCs or PTZ) considered after <48â¯h of empirical antibiotic therapy. The main outcome was the rate of therapeutic failure (impaired clinical response under treatment and/or a relapse of pulmonary infection). The secondary outcome was a secondary acquisition of 3GCs resistance. RESULTS: Over the study period, 244 patients were included; 56 (23%) experienced therapeutic failure. In the non-adjusted cohort, the rate of therapeutic failure and emergence of resistance were significantly higher in the 3GCs group (32 vs. 18%, pâ¯=â¯.011 and 13 vs. 5%, pâ¯=â¯.035, respectively). In the propensity score-matched population, the use of 3GCs was associated with higher rates of therapeutic failure (HRâ¯=â¯1.61 [1.27-2.07]). The secondary de-escalation to 3GCs after 48â¯h of PTZ as a first-line antibiotic therapy was not associated with increased rate of emergence of resistance. CONCLUSION: Our study confirms that 3GCs should be avoided as first-line antibiotic therapy in wild-type AmpC-producing Enterobacterales pulmonary infections.
Asunto(s)
Proteínas Bacterianas/metabolismo , Cefalosporinas/uso terapéutico , Enfermedad Crítica , Infección Hospitalaria/tratamiento farmacológico , Combinación Piperacilina y Tazobactam/uso terapéutico , Neumonía Asociada al Ventilador/tratamiento farmacológico , beta-Lactamasas/metabolismo , Anciano , Antibacterianos/uso terapéutico , Enterobacter , Composición Familiar , Femenino , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Ácido Penicilánico , Estudios Retrospectivos , Ventiladores MecánicosRESUMEN
BACKGROUND: Augmented renal clearance (ARC) is recognized as a leading cause of ß-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased ß-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP). METHODS: In this single-center, retrospective study, every ARC patient treated by ß-lactam for a first episode of HAP-VAP was included during two 15-month periods, before (Control period) and after (Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome. RESULTS: During the study period, 177 patients were included (control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15-0.81), p = 0.014. No antibiotic side effect was reported during the treatment period. CONCLUSIONS: Higher than licensed dosing regimens of ß-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.
Asunto(s)
Neumonía/tratamiento farmacológico , Resultado del Tratamiento , beta-Lactamas/administración & dosificación , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Enfermedad Crítica/terapia , Relación Dosis-Respuesta a Droga , Femenino , Neumonía Asociada a la Atención Médica/tratamiento farmacológico , Neumonía Asociada a la Atención Médica/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neumonía/epidemiología , Neumonía Asociada al Ventilador/tratamiento farmacológico , Neumonía Asociada al Ventilador/epidemiología , Estudios Retrospectivos , beta-Lactamas/uso terapéuticoAsunto(s)
Cardiotónicos/uso terapéutico , Angiografía Cerebral , Angiografía por Tomografía Computarizada , Milrinona/uso terapéutico , Simendán/uso terapéutico , Hemorragia Subaracnoidea/complicaciones , Vasoespasmo Intracraneal/tratamiento farmacológico , Aneurisma Roto/complicaciones , Aneurisma Roto/diagnóstico por imagen , Cardiotónicos/administración & dosificación , Pérdida de Líquido Cefalorraquídeo , Resistencia a Medicamentos , Sustitución de Medicamentos , Quimioterapia Combinada , Embolización Terapéutica , Humanos , Infusiones Intravenosas , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/terapia , Presión Intracraneal/efectos de los fármacos , Sulfato de Magnesio/administración & dosificación , Sulfato de Magnesio/uso terapéutico , Masculino , Persona de Mediana Edad , Milrinona/administración & dosificación , Milrinona/efectos adversos , Nimodipina/administración & dosificación , Nimodipina/uso terapéutico , Simendán/efectos adversos , Hemorragia Subaracnoidea/diagnóstico por imagen , Vasoespasmo Intracraneal/diagnóstico por imagen , Vasoespasmo Intracraneal/etiología , Disfunción Ventricular Izquierda/inducido químicamenteRESUMEN
The objective of the present study was to determine whether augmented renal clearance (ARC) impacts negatively on ceftriaxone pharmacokinetic (PK)/pharmacodynamic (PD) target attainment in critically ill patients. Over a 9-month period, all critically ill patients treated with ceftriaxone were eligible. During the first 3 days of antimicrobial therapy, every patient underwent 24-h creatinine clearance (CLCR) measurements and therapeutic drug monitoring of unbound ceftriaxone. ARC was defined by a CLCR of ≥150 ml/min. Empirical underdosing was defined by a trough unbound ceftriaxone concentration under 2 mg/liter (percentage of the time that the concentration of the free fraction of drug remained greater than the MIC [fT>MIC], 100%). Monte Carlo simulation (MCS) was performed to determine the probability of target attainment (PTA) of different dosing regimens for various MICs and three groups of CLCR (<150, 150 to 200, and >200 ml/min). Twenty-one patients were included. The rate of empirical ceftriaxone underdosing was 62% (39/63). A CLCR of ≥150 ml/min was associated with empirical target underdosing with an odds ratio (OR) of 8.8 (95% confidence interval [CI] = 2.5 to 30.7; P < 0.01). Ceftriaxone PK concentrations were best described by a two-compartment model. CLCR was associated with unbound ceftriaxone clearance (P = 0.02). In the MCS, the proportion of patients who would have failed to achieve a 100% fT>MIC was significantly higher in ARC patients for each dosage regimen (OR = 2.96; 95% CI = 2.74 to 3.19; P < 0.01). A dose of 2 g twice a day was best suited to achieve a 100% fT>MIC When targeting a 100% fT>MIC for the less susceptible pathogens, patients with a CLCR of ≥150 ml/min remained at risk of empirical ceftriaxone underdosing. These data emphasize the need for therapeutic drug monitoring in ARC patients.
Asunto(s)
Antibacterianos/farmacocinética , Ceftriaxona/farmacocinética , Creatinina/orina , Monitoreo de Drogas/métodos , Tasa de Depuración Metabólica/fisiología , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Ceftriaxona/administración & dosificación , Ceftriaxona/uso terapéutico , Cuidados Críticos , Enfermedad Crítica , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana EdadAsunto(s)
Relación Dosis-Respuesta a Droga , Combinación Piperacilina y Tazobactam/administración & dosificación , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Enfermedad Crítica/terapia , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica/fisiología , Pruebas de Sensibilidad Microbiana/métodos , Pruebas de Sensibilidad Microbiana/estadística & datos numéricos , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Combinación Piperacilina y Tazobactam/análisis , Combinación Piperacilina y Tazobactam/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: The aim of the present study was to explore the relationship between creatinine clearance (ClCr), cardiac index (CI) and renal vascular index (RVI) in order to assess the potential mechanisms driving ARC in critically ill trauma patient. The secondary objective was to assess the performance of RVI for prediction of ARC. METHODS: Every trauma patient who underwent cardiac and renal ultrasound measurements during their initial ICU management was retrospectively reviewed over a 3-month period. ARC was defined by a 24-hr measured ClCr ≥ 130 mL/min/1.73m2. A mixed effect model was constructed to explore covariates associated with ClCr over time. The performance of RVI for prediction of ARC was assessed by receiver operating characteristic (ROC) curve and compared to the ARCTIC (ARC in trauma intensive care) predictive scoring model. RESULTS: Thirty patients, contributing for 121 coupled physiologic data, were retrospectively analysed. There was a significant correlation between ClCr values and RVI (r = -0.495; P = 0.005) but not between ClCr and CI values (r = 0.023; P = 0.967) at day 1. Using a mixed effect model, only age remained associated with ClCr variations over time. The area under the ROC curve of RVI for predicting ARC was 0.742 (95% CI: 0.649-0.834; P < 0.0001), with statistical difference when compared to the ROC curve of ARCTIC [0.842 (0.771-0.913); P < 0.0001]. CONCLUSION: Ultrasonic evaluation of CI and RVI did not allow approaching the haemodynamic mechanisms responsible for ARC in patients. RVI was inaccurate and not better than clinical score for predicting ARC.
Asunto(s)
Riñón/fisiopatología , Heridas y Lesiones/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Creatinina , Enfermedad Crítica , Femenino , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Introduction The main objective of this prospective study was to assess the incidence of chronic pain and long-term respiratory disability in a single-center cohort of severe blunt chest trauma patients. Methods Over a 10-month period, all consecutive blunt chest trauma patients admitted in Intensive Care Unit (ICU) were screened to participate in a 3-month and 12-month follow-up. The following variables were prospectively assessed: persistence of chronic chest pain requiring regular used of analgesics, neuropathic pain, respiratory disability, physical and mental health status. Univariate and multivariable analysis were conducted to assess variables associated with chronic chest pain, neuropathic chest pain and respiratory disability. Results During the study period, 65 patients were included in the study. Chronic chest pain and respiratory disability were reported in 62% and 57% of patients respectively at 3 months postinjury. Neuropathic pain was reported in 22% of patients, associated with higher impairment of quality of life. A thoracic trauma severity score ≥12 and a pain score ≥4 at SICU discharge were the only variables significantly associated with the occurrence of neuropathic pain at 3 months (OR = 7 [2-32], p = 0.01 and OR = 16 [4-70], p < 0.0001). Conclusion According to the current study, chronic pain and long-term respiratory disability are very common after severe blunt chest trauma patients. Special attention should be paid to neuropathic pain, frequently under-diagnosed and responsible for significant impairment of quality of life.