Thyroid Disfunction in Critically Ill COVID-19 Patients. Relationship with In-Hospital Mortality.

The incidence of thyroid disfunction has not been analyzed in critically ill COVID-19 patients. Our objective was to analyze the relationship of the thyroid profile and in-hospital mortality in critically ill COVID-19 patients. This was a prospective single-center study involving critically ill COVID-19 patients admitted to the ICU of a tertiary University Hospital. Thyroid hormones were measured through drawing blood samples from a central venous catheter at ICU admission and on the fifth day. A multiple logistic regression analysis was performed to analyze the variables associated with mortality. The ability of the different thyroid hormones to predict in-hospital mortality was evaluated by calculating the receiver operating characteristics (ROCs) and the area under the curve (AUC). A total of 78 patients were included in the study at ICU admission; 72 had their thyroid profile measured at day 5. In-hospital mortality reached 29.5%. Multiple logistic regression analysis showed that variables associated with mortality were age and prior beta-blocker therapy at ICU admission and age fT4 at day 5. The AUC for in-hospital mortality predictions of fT4 at day 5 was 0.69. Thyroid responses are commonly observed in critically ill COVID-19 patients. fT4 at day 5 after ICU admission was associated with mortality.

Successful weaning from continuous renal replacement therapy. Associated risk factors.

PURPOSE: To identify risk factors of successful continuous renal replacement therapy (CRRT) weaning and to evaluate the effect of furosemide in the recovery of urine output after CRRT stop. MATERIALS AND METHODS: Retrospective, observational study of critical patients treated with CRRT. Weaning tests (WT) were classified in two groups: successful (urine output was recovered and CRRT was not required again) and failed (CRRT was required again). A multiple logistic regression model was used to identify risk factors of successful CRRT WT. The prediction ability was assessed with the area under the receiver operating characteristic curves (AUC-ROC). RESULTS: Eighty-six patients underwent 101 CRRT WT. The multivariate model identified that the risk factors of successful CRRT weaning were sex and 6h-urine output after CRRT stop. The AUC-ROC was 0.81 (0.72-0.90) for 6h-urine output before and 0.91 (0.84-0.96) for 6h-urine output after CRRT stop. The AUC-ROC for 6h-urine output after WT to predict successful CRRT weaning were 0.94 (0.88-1.0) in patients who received furosemide and 0.85 (0.72-0.99) in patients who did not. CONCLUSIONS: Urine output after CRRT stop was the main risk factor of successful CRRT weaning. Administration of furosemide increased the strength of this association.

Hyperlactatemia in ICU patients: Incidence, causes and associated mortality.

PURPOSE: To describe the incidence, causes and associated mortality of hyperlactatemia in critically ill patients and to evaluate the association between lactate clearance and in-hospital survival. METHODS: Retrospective cohort study of patients with hyperlactatemia admitted to the ICU. Hyperlactatemia was defined as a blood lactate concentration ≥5mmol/L and high-grade hyperlactatemia a lactate level ≥10mmol/L. Lactate clearance was calculated as the percentage of decrease in lactate concentration from the peak value. RESULTS: Of 10,123 patients, 1373 (13.6%) had lactate concentration ≥5mmol/L, and 434(31.6%) of them had ≥10mmol/L. The most common causes of hyperlactatemia were sepsis/septic shock and post-cardiac surgery. An association was found between lactate concentration and in-hospital mortality (p<0.001). The area under the receiver-operating-characteristics (ROC) of lactate concentration and the optimal cut off to predict mortality were 0.72 (0.70-0.75) and 8.6mmol/L, respectively. ROC analysis for lactate clearance to predict in-hospital survival showed that the best area under the curve was obtained at 12h: 0.67 (95% confidence interval 0.59-0.75). CONCLUSIONS: Hyperlactatemia was common and associated with a high mortality in critically ill patients. Lactate clearance had limited utility for predicting in-hospital survival.

Severe trauma in the geriatric population.

Geriatric trauma constitutes an increasingly recognized problem. Aging results in a progressive decline in cellular function which leads to a loose of their capacity to respond to injury. Some medications commonly used in this population can mask or blunt the response to injury. Falls constitute the most common cause of trauma and the leading cause of trauma-related deaths in this population. Falls are complicated by the widespread use of antiplatelets and anticoagulants, especially in patients with brain injury. Under-triage is common in this population. Evaluation of frailty could be helpful to solve this issue. Appropriate triaging and early aggressive management with correction of coagulopathy can improve outcome. Limitation of care and palliative measures must be considered in cases with a clear likelihood of poor prognosis.

Prophylaxis Versus Treatment Use of Laxative for Paralysis of Lower Gastrointestinal Tract in Critically Ill Patients.

GOALS: To evaluate the prevalence of lower gastrointestinal tract paralysis and to compare the success to achieve defecation between treatment and prophylaxis strategies. BACKGROUND: Laxatives use is commonly the first-level measure to achieve defecation in critically ill patients with lower gastrointestinal tract paralysis. Studies comparing prophylaxis versus treatment of lower gastrointestinal tract paralysis have not been performed yet. STUDY: We designed 3 sequential phases of 4 months each: observational phase, treatment phase, and prophylaxis phase. First-level measure was intermittent polyethylene glycol (PEG) 4000 by nasogastric tube. Second-level measures were enema, neostigmine, and continuous PEG. Primary endpoints were the prevalence of constipation for the observational phase and the number of patients that failed to achieve defecation with first-level measures for the treatment and prophylaxis phases. RESULTS: Paralysis of lower gastrointestinal tract in the observational phase was found in 57 of 63 patients (90.5%). Failure to achieve defecation with the first-level measure occurred in 16 of 64 patients (25%) in the treatment phase and in 6 of 70 patients (8.6%) in the prophylaxis phase (P=0.01). Eighteen measures of second level were applied in the treatment phase and 6 in the prophylaxis phase. CONCLUSIONS: Paralysis of the lower gastrointestinal tract in mechanically ventilated ICU patients is common. PEG given as prophylaxis on the first day after mechanical ventilation is associated with faster resolution of paralysis of gastrointestinal tract than PEG given as a treatment on day 4.

A simplified equation for total energy expenditure in mechanically ventilated critically ill patients / Ecuación simplificada para el cálculo del gasto energético total en pacientes críticos con ventilación mecánica

Introduction: 'tight calorie control' concept arose to avoid over- and under-feeding of patients. Objective: to describe and validate a simplified predictive equation of total energy expenditure (TEE) in mechanically ventilated critically ill patients. Methods: this was a secondary analysis of measurements of TEE by indirect calorimetry in critically ill patients. Patients were allocated in a 2:1 form by a computer package to develop the new predictive equation TEE (prediction cohort) and the validation cohort. Indirect calorimetry was performed with three different calorimeters: the Douglas-bag, a metabolic computer and the Calorimet®. We developed a new TEE predictive equation using measured TEE (in kcal/kg/d) as dependent variable and as independent variables different factors known to influence energy expenditure: age, gender, body mass index (BMI) and type of injury. Results: prediction cohort: 179 patients. Validation cohort: 91 patients. The equation was: TEEPE (kcal/Kg/d) = 33 - (3 x A) - (3 x BMI) - (1 x G). Where: A (age in years): ≤ 50 = 0; > 50 = 1. BMI (Kg/m2 ): 18.5 - 24.9 = 0; 25 - 29.9 = 1; 30 - 34.9 = 2;35 - 39.9 = 3. G (gender): male = 0; female = 1. The bias (95% CI) was -0.1 (-1.0 - 0.7) kcal/kg/d and the limits of agreement (± 2SD) were -8.0 to 7.8 kcal/kg/d. Predicted TEE was accurate (within 85% to 115%) in 73.6% of patients. Conclusion: the new predictive equation was acceptable to predict TEE in clinical practice for most mechanically ventilated critically ill patients (AU)

Introducción: el concepto de 'control calórico estricto' surgió para evitar la excesiva y la deficiente nutrición de los pacientes. Objetivo: describir y validar una ecuación simplificada para el cálculo del gasto energético total (GET) en pacientes críticos con ventilación mecánica. Métodos: análisis secundario de las mediciones de GET por calorimetría indirecta en pacientes críticos. Los pacientes fueron asignados de forma 2:1 por un paquete estadístico; el primer grupo se empleó para desarrollar la nueva ecuación predictiva del GET (grupo predictivo) y el segundo para validarla (grupo validación). La calorimetría indirecta se realizó con tres calorímetros diferentes: la bolsa de Douglas, un computador metabólico y el equipo Calorimet®. Hemos desarrollado la nueva ecuación predictiva del GET utilizando el GET medido (en kcal/kg/d), como variable dependiente, y como variables independientes los diferentes factores que influyen en el gasto energético: edad, género, índice de masa corporal (IMC) y tipo de lesión. Resultados: el grupo de predicción incluyó 179 pacientes y el de validación 91 pacientes. La ecuación predictiva fue: GETEP = 33 - (3 x E) - (3 x IMC) - (1 x G). Donde: E (edad en años): ≤ 50 = 0; > 50 = 1. IMC (kg / m2): 18,5- 24,9 = 0; 25-29,9 = 1; 30-34,9 = 2; 35-39,9 = 3. G (género): hombre = 0; mujer = 1. El sesgo (IC del 95%) entre el GET medido y el predicho fue de -0,1 (-1,0 a 0,7) kcal/ kg/día y los límites de acuerdo (± 2SD) fueron -8,0 a 7,8 kcal/kg/d. El GET por la ecuación predictiva fue preciso (entre el 85% y el 115%) en el 73,6% de los pacientes. Conclusiones: La nueva ecuación predictiva fue aceptable para predecir el GET de la mayoría de pacientes críticos con ventilación mecánica en la práctica clínica (AU)

A SIMPLIFIED EQUATION FOR TOTAL ENERGY EXPENDITURE IN MECHANICALLY VENTILATED CRITICALLY ILL PATIENTS.

INTRODUCTION: "tight calorie control" concept arose to avoid over- and under-feeding of patients. OBJECTIVE: to describe and validate a simplified predictive equation of total energy expenditure (TEE) in mechanically ventilated critically ill patients. METHODS: this was a secondary analysis of measurements of TEE by indirect calorimetry in critically ill patients. Patients were allocated in a 2:1 form by a computer package to develop the new predictive equation TEE (prediction cohort) and the validation cohort. Indirect calorimetry was performed with three different calorimeters: the Douglas-bag, a metabolic computer and the CalorimetR. We developed a new TEE predictive equation using measured TEE (in kcal/kg/d) as dependent variable and as independent variables different factors known to influence energy expenditure: age, gender, body mass index (BMI) and type of injury. RESULTS: prediction cohort: 179 patients. Validation cohort: 91 patients. The equation was: TEEPE (kcal/Kg/d) = 33 - (3 x A) - (3 x BMI) - (1 x G). Where: A (age in years): ≤ 50 = 0; > 50 = 1. BMI (Kg/m2): 18.5 - 24.9 = 0; 25 - 29.9 = 1; 30 - 34.9 = 2; 35 - 39.9 = 3. G (gender): male = 0; female = 1. The bias (95% CI) was -0.1 (-1.0 - 0.7) kcal/kg/d and the limits of agreement (} 2SD) were -8.0 to 7.8 kcal/kg/d. Predicted TEE was accurate (within 85% to 115%) in 73.6% of patients. CONCLUSION: the new predictive equation was acceptable to predict TEE in clinical practice for most mechanically ventilated critically ill patients.

Introducción: el concepto de "control calorico estricto" surgio para evitar la excesiva y la deficiente nutricion de los pacientes. Objetivo: describir y validar una ecuacion simplificada para el calculo del gasto energetico total (GET) en pacientes criticos con ventilacion mecanica. Métodos: analisis secundario de las mediciones de GET por calorimetria indirecta en pacientes criticos. Los pacientes fueron asignados de forma 2:1 por un paquete estadistico; el primer grupo se empleo para desarrollar la nueva ecuacion predictiva del GET (grupo predictivo) y el segundo para validarla (grupo validacion). La calorimetria indirecta se realizo con tres calorimetros diferentes: la bolsa de Douglas, un computador metabolico y el equipo CalorimetR. Hemos desarrollado la nueva ecuacion predictiva del GET utilizando el GET medido (en kcal/kg/d), como variable dependiente, y como variables independientes los diferentes factores que influyen en el gasto energetico: edad, genero, indice de masa corporal (IMC) y tipo de lesion. Resultados: el grupo de prediccion incluyo 179 pacientes y el de validacion 91 pacientes. La ecuacion predictiva fue: GETEP = 33 - (3 x E) - (3 x IMC) - (1 x G). Donde: E (edad en anos): ≤ 50 = 0; > 50 = 1. IMC (kg / m2): 18,5- 24,9 = 0; 25-29,9 = 1; 30-34,9 = 2; 35-39,9 = 3. G (genero): hombre = 0; mujer = 1. El sesgo (IC del 95%) entre el GET medido y el predicho fue de -0,1 (-1,0 a 0,7) kcal/ kg/dia y los limites de acuerdo (} 2SD) fueron -8,0 a 7,8 kcal/kg/d. El GET por la ecuacion predictiva fue preciso (entre el 85% y el 115%) en el 73,6% de los pacientes. Conclusiones: La nueva ecuacion predictiva fue aceptable para predecir el GET de la mayoria de pacientes criticos con ventilacion mecanica en la practica clinica.

Role of Respiratory Drive in Hyperoxia-Induced Hypercapnia in Ready-to-Wean Subjects With COPD.

BACKGROUND: Hyperoxia-induced hypercapnia in subjects with COPD is mainly explained by alterations in the ventilation/perfusion ratio. However, it is unclear why respiratory drive does not prevent CO2 retention. Some authors have highlighted the importance of respiratory drive in CO2 increases during hyperoxia. The aim of the study was to examine the effects of hyperoxia on respiratory drive in subjects with COPD. METHODS: Fourteen intubated, ready-to-wean subjects with COPD were studied during normoxia and hyperoxia. A CO2 response test was then performed with the rebreathing method to measure the hypercapnic drive response, defined as the ratio of change in airway-occlusion pressure 0.1 s after the start of inspiratory flow (ΔP(0.1)) to change in P(aCO2) (ΔP(aCO2)), and the hypercapnic ventilatory response, defined as the ratio of change in minute volume (ΔV̇(E)) to ΔP(aCO2). RESULTS: Hyperoxia produced a significant increase in P(aCO2) (55 ± 9 vs 58 ± 10 mm Hg, P = .02) and a decrease in pH (7.41 ± 0.05 vs 7.38 ± 0.05, P = .01) compared with normoxia, with a non-significant decrease in V̇(E) (9.9 ± 2.9 vs 9.1 ± 2.3 L/min, P = .16) and no changes in P(0.1) (2.85 ± 1.40 vs 2.82 ± 1.16 cm H2O, P = .97) The correlation between hyperoxia-induced changes in V̇(E) and P(aCO2) was r(2) = 0.38 (P = .02). Median ΔP(0.1)/ΔP(aCO2) and ΔV̇(E)/ΔP(aCO2) did not show significant differences between normoxia and hyperoxia: 0.22 (0.12-0.49) cm H2O/mm Hg versus 0.25 (0.14-0.34) cm H2O/mm Hg (P = .30) and 0.37 (0.12-0.54) L/min/mm Hg versus 0.35 (0.12-0.96) L/min/mm Hg (P = .20), respectively. CONCLUSIONS: In ready-to-wean subjects with COPD exacerbations, hyperoxia is followed by an increase in P(aCO2), but it does not significantly modify the respiratory drive or the ventilatory response to hypercapnia.

Role of Elevated Aminotransferases in ICU Patients with Rhabdomyolysis.

To evaluate whether patients with rhabdomyolysis and serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) higher than 1000 IU/L had higher mortality that patients with low aminotransferases. Retrospective analysis of intensive care unit patients with rhabdomyolysis [creatine kinase (CK) higher than 5000 IU/L]. Patients were classified in two groups: low aminotransferases group, when AST and ALT were equal or lower to 1000 IU/L, and elevated aminotransferases group, when AST or ALT was above 1000 IU/L. Forty-six out of 189 patients included in the analysis (24.3%) had elevated aminotransferases. The mortality of patients with rhabdomyolysis was 25.9 per cent, being higher in patients with elevated aminotransferases compared with patients with low aminotransferases (60.9% vs 14.7%; P < 0.001). Mortality stratified by quartiles of CK in patients with low aminotransferases was independent of the level of CK (P = 0.67). Logistic regression analysis showed that the independent variables associated with mortality were Simplified Acute Physiology Score II [1.11 (1.07-1.16) for each point of increase, P < 0.001], the international normalized ratio value [4.2 (1.6-10.7) for each point of increase, P = 0.003], and the need of renal replacement therapy [5.4 (1.7-17.2), P = 0.004]. Patients with rhabdomyolysis with elevated serum aminotransferases had higher mortality than patients with low serum aminotransferase levels.

A randomized trial of intravenous glutamine supplementation in trauma ICU patients.

PURPOSE: To evaluate the effect of the intravenous (i.v.) L-alanyl-L-glutamine dipeptide supplementation during 5 days on clinical outcome in trauma patients admitted to the intensive care unit (ICU). METHODS: This was a prospective, randomized, double-blind, multicenter trial. Glutamine was not given as a component of nutrition but as an extra infusion. The primary outcome variable was the number of new infections within the first 14 days. RESULTS: We included 142 patients. There were no differences between groups in baseline characteristics. Up to 62 % of the patients in the placebo group and 63 % in the treatment group presented confirmed infections (p = 0.86). ICU length of stay was 14 days in both groups (p = 0.54). Hospital length of stay was 27 days in the placebo group and 29 in the treatment group (p = 0.88). ICU mortality was 4.2 % in both groups (p = 1). Sixty percent of the patients presented low glutamine levels before randomization. At the end of the treatment (6th day), 48 % of the patients maintained low glutamine levels (39 % of treated patients vs. 57 % in the placebo group). Patients with low glutamine levels at day 6 had more number of infections (58.8 vs. 80.9 %; p = 0.032) and longer ICU (9 vs. 20 days; p < 0.01) and hospital length of stay (24 vs. 41 days; p = 0.01). CONCLUSIONS: There was no benefit with i.v. L-alanyl-L-glutamine dipeptide supplementation (0.5 g/kg body weight/day of the dipeptide) during 5 days in trauma patients admitted to the ICU. The i.v. glutamine supplementation was not enough to normalize the plasma glutamine levels in all patients. Low plasma glutamine levels at day 6 were associated with a worse outcome.

Central respiratory drive in patients with neuromuscular diseases.

BACKGROUND: The contribution of the central respiratory drive in the hypercapnic respiratory failure of neuromuscular diseases (NMD) is controversial. OBJECTIVE: To compare the CO2 response and the duration of weaning of mechanical ventilation between a group of NMD patients and a group of quadriplegic patients due to ICU-acquired weakness (ICU-AW). METHODS: We prospectively studied 16 subjects with NMD and 26 subjects with ICU-AW ready for weaning, using the method of the re-inhalation of expired air. We measured the hypercapnic drive response, defined as the ratio of change in airway occlusion pressure 0.1 second after the start of inspiration (ΔP0.1) to the change in Paco2 (ΔPaco2), and the hypercapnic ventilatory response, defined as the ratio of the change in minute ventilation (ΔVe) to ΔPaco2. We considered a value of ≤ 0.19 cm H2O/mm Hg as reduced hypercapnic drive response. RESULTS: Hypercapnic drive response (ΔP0.1/ΔPaco2 = 0.14 ± 0.08 cm H2O/mm Hg vs 0.37 ± 0.27 cm H2O/mm Hg, P = .002) and hypercapnic ventilatory response (ΔVe/ΔPaco2 = 0.21 ± 0.19 L/min/mm Hg vs 0.44 ± 0.40 L/min/mm Hg, P = .02) were lower in the NMD than in the ICU-AW subjects. Duration of weaning values, according to the Kaplan-Meier curves, were similar in both groups (Log-rank = 0.03, P = .96). Eleven NMD (69%) and 9 ICU-AW (35%) subjects had hypercapnic drive response ≤ 0.19 cm H2O/mm Hg. The duration of weaning was longer in subjects with hypercapnic drive response ≤ 0.19 cm H2O/mm Hg (log-rank = 15.4, P < .001). CONCLUSIONS: Subjects with acute hypercapnic respiratory failure due to NMD had reduced hypercapnic drive response, compared to ICU-AW subjects. The duration of weaning was longer in subjects with reduced hypercapnic drive response.

Potential effects of corticosteroids on physiological dead-space fraction in acute respiratory distress syndrome.

BACKGROUND: Increased dead-space fraction is common in patients with persistent acute respiratory distress syndrome (ARDS). We evaluated the changes in the oxygenation and dead-space fraction in patients with persistent ARDS after corticosteroid therapy. METHODS: This was a non-randomized non-placebo, controlled observational study including 19 patients with persistent ARDS treated with corticosteroids. We measured P(aO(2))/F(IO(2)) and dead-space fraction at days 0, 4, and 7 after corticosteroids treatment (methylprednisolone) initiation. Patients were classified in intermediate group when corticosteroids were initiated between days 8-14 after ARDS onset, and in late group when initiated after 14 days. RESULTS: Mean time from the diagnosis of the ARDS to methylprednisolone treatment was 11 ± 2 days in the intermediate group (10 patients) and 21 ± 8 days in the late group (9 patients). When comparing days 0, 4, and 7 after methylprednisolone treatment, we found an increase in the P(aO(2))/F(IO(2)) (145 ± 64 mm Hg, 190 ± 68 mm Hg, and 226 ± 84 mm Hg, respectively, P < .001) and a decrease in the physiological dead-space fraction (0.66 ± 0.10, 0.58 ± 0.12, and 0.53 ± 0.11, respectively, P < .001). No differences were found between the intermediate and late groups. CONCLUSIONS: In patients with persistent ARDS, the increase in oxygenation was accompanied by a decrease in the dead-space fraction after a few days of corticosteroid treatment. To confirm potential benefit of corticosteroids on physiological parameters and mortality will require a powered randomized placebo controlled trial.

Response to the high-dose corticotrophin stimulation test depends on plasma adrenocotropin hormone levels in septic shock.

PURPOSE: The use of the high-dose corticotrophin stimulation test (HDCST) as a guide to use low-dose steroid therapy in septic shock is controversial. The adrenocotropin hormone (ACTH) constitutes the immediate stimuli to produce cortisol. We evaluated the correlation of the response to the HDCST with plasma ACTH levels in patients with septic shock. METHODS: This is a retrospective review of 102 patients with septic shock in which adrenal function was evaluated using the HDCST and plasma ACTH levels were measured. Patients with a δ cortisol of 9 µg/dL or less were considered as nonresponders or with subnormal response. The association between plasma ACTH levels and the response to the HDCST was investigated. RESULTS: Sixty-four patients (62.7%) had a subnormal response. Plasma ACTH levels were higher in patients with subnormal response (19.8 [11.7-31.4] vs 10.0 [7.0-21.2] pg/mL; P = .002). Patients in the highest quartile of plasma ACTH had lower δ cortisol (P = .014) and higher percentage of subnormal response (P = .005). The optimal cutoff point of plasma ACTH level with fewest false classifications was 10 pg/mL (sensitivity, 0.83 [95% confidence interval, 074-0.90] and specificity, 0.50 [95% confidence interval, 0.74-0.90]). CONCLUSION: Patients with septic shock with higher plasma ACTH values presented a subnormal response to the HDCST. The number of patients who failed to the HDCST was higher as plasma ACTH increased.

CO2 response and duration of weaning from mechanical ventilation.

BACKGROUND: The CO2 response test measures the hypercapnic drive response (which is defined as the ratio of the change in airway-occlusion pressure 0.1 s after the start of inspiratory flow [ΔP(0.1)] to the change in P(aCO2) [ΔP(aCO2)]), and the hypercapnic ventilatory response (which is defined as the ratio of the change in minute volume to ΔP(aCO2)). OBJECTIVE: In mechanically ventilated patients ready for a spontaneous breathing trial, to investigate the relationship between CO2 response and the duration of weaning. METHODS: We conducted the CO2 response test and measured maximum inspiratory pressure (P(Imax)) and maximum expiratory pressure (P(Emax)) in 102 non-consecutive ventilated patients. We categorized the patients as either prolonged weaning (weaning duration > 7 d) or non-prolonged weaning (≤ 7 d). RESULTS: Twenty-seven patients had prolonged weaning. Between the prolonged and non-prolonged weaning groups we found differences in hypercapnic drive response (0.22 ± 0.16 cm H2O/mm Hg vs 0.47 ± 0.22 cm H2O/mm Hg, respectively, P < .001) and hypercapnic ventilatory response (0.25 ± 0.23 L/min/mm Hg vs 0.53 ± 0.33 L/min/mm Hg, respectively, P < .001). The optimal cutoff points to differentiate between prolonged and non-prolonged weaning were 0.19 cm H2O/mm Hg for hypercapnic drive response, and 0.15 L/min/mm Hg for hypercapnic ventilatory response. Assessed with the Cox proportional hazards model, both hypercapnic drive response and hypercapnic ventilatory response were independent variables associated with the duration of weaning. The hazard ratio of weaning success was 16.7 times higher if hypercapnic drive response was > 0.19 cm H2O/mm Hg, and 6.3 times higher if hypercapnic ventilatory response was > 0.15 L/min/mm Hg. Other variables (P(0.1), P(Imax), and P(Emax)) were not associated with the duration of the weaning. CONCLUSIONS: Decreased CO2 response, as measured by hypercapnic drive response and hypercapnic ventilatory response, are associated with prolonged weaning.

Hypoxic hepatitis in critically ill patients: incidence, etiology and risk factors for mortality.

PURPOSE: Hypoxic hepatitis may be induced by hemodynamic instability or arterial hypoxemia in critically ill patients. We investigated the incidence, etiology, association with systemic ischemic injury and risk factors for mortality in this population. METHODS: Retrospective analysis of patients with hypoxic hepatitis admitted to a multidisciplinary intensive care unit (ICU) of a university hospital. Hypoxic hepatitis was defined as the existence of a compatible clinical setting (cardiocirculatory failure or arterial hypoxemia) and aminotransferase levels higher than 1000 IU/L. RESULTS: During the 8-year study period, 182 out of the 7674 patients admitted presented hypoxic hepatitis (2.4%). The most common cause was septic shock. The rate of in-hospital mortality in hypoxic hepatitis was 61.5% (112 patients), and was higher in patients with septic shock (83.3%) and cardiac arrest (77.7%). Ischemic pancreatitis (25.6%), rhabdomyolysis (41.2%) and renal failure (67.2%) were common in these patients. Risk factors of mortality were prolonged INR (p = 0.005), need for renal replacement therapy (p = 0.001) and septic shock (p = 0.005). CONCLUSIONS: Hypoxic hepatitis was not a rare condition, and was frequently accompanied by multiorgan injury, with high mortality. Risk factors for increased mortality were prolonged INR, need for renal replacement therapy, and septic shock.

Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit.

INTRODUCTION: The use of glutamine as a dietary supplement is associated with a reduced risk of infection. We hypothesized that the underlying mechanism could be an increase in the expression and/or functionality of Toll-like receptors (TLR), key receptors sensing infections. The objective of this study was to evaluate whether glutamine supplementation alters the expression and functionality of TLR2 and TLR4 in circulating monocytes of trauma patients admitted to the intensive care unit (ICU). METHODS: We designed a prospective, randomized and single-blind study. Twenty-three patients received parenteral nutrition (TPN) with a daily glutamine supplement of 0.35 g/kg. The control group (20 patients) received an isocaloric-isonitrogenated TPN. Blood samples were extracted before treatment, at 6 and 14 days. Expression of TLR2 and TLR4 was determined by flow cytometry. Monocytes were stimulated with TLR specific agonists and cytokines were measured in cell culture supernatants. Phagocytic ability of monocytes was also determined. RESULTS: Basal characteristics were similar in both groups. Monocytes from patients treated with glutamine expressed the same TLR2 levels as controls before treatment (4.9 ± 3.5 rmfi vs. 4.3 ± 1.9 rmfi, respectively; P = 0.9), at Day 6 (3.8 ± 2.3 rmfi vs. 4.0 ± 1.7 rmfi, respectively; P = 0.7) and at Day 14 (4.1 ± 2.1 rfim vs. 4.6 ± 1.9 rmfi, respectively; P = 0.08). TLR4 levels were not significantly different between the groups before treatment: (1.1 ± 1 rmfi vs 0.9 ± 0.1 rmfi respectively; P = 0.9), at Day 6 (1.1 ± 1 rmfi vs. 0.7 ± 0.4 rmfi respectively; P = 0.1) and at Day 14 (1.4 ± 1.9 rmfi vs. 1.0 ± 0.6 rmfi respectively; P = 0.8). No differences in cell responses to TLR agonists were found between groups. TLR functionality studied by phagocytosis did not vary between groups. CONCLUSIONS: In trauma patients in the intensive care unit, TPN supplemented with glutamine does not improve the expression or the functionality of TLRs in peripheral blood monocytes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01250080.

Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO2 response and acetazolamide treatment effects.

OBJECTIVE: In obesity-hypoventilation-syndrome patients mechanically ventilated for hypercapnic respiratory failure we investigated the relationship between CO2 response, body mass index, and plasma bicarbonate concentration, and the effect of acetazolamide on bicarbonate concentration and CO2 response. METHODS: CO2 response tests and arterial blood gas analysis were performed in 25 patients ready for a spontaneous breathing test, and repeated in a subgroup of 8 patients after acetazolamide treatment. CO2 response test was measured as (1) hypercapnic drive response (the ratio of the change in airway occlusion pressure 0.1 s after the start of inspiratory flow to the change in P(aCO2)), and (2) hypercapnic ventilatory response (the ratio of the change in minute volume to the change in P(aCO2)). RESULTS: We did not find a significant relationship between CO2 response and body mass index. Patients with higher bicarbonate concentration had a more blunted CO2 response. Grouping the patients according to the first, second, and third tertiles of the bicarbonate concentration, the hypercapnic drive response was 0.32 ± 0.17 cm H2O/mm Hg, 0.22 ± 0.15 cm H2O/mm Hg, and 0.10 ± 0.06 cm H2O/mm Hg, respectively (P = .01), and hypercapnic ventilatory response was 0.46 ± 0.23 L/min/mm Hg, 0.48 ± 0.36 L/min/mm Hg, and 0.22 ± 0.16 L/min/mm Hg, respectively (P = .04). After acetazolamide treatment, bicarbonate concentration was reduced by 8.4 ± 3.0 mmol/L (P = .01), and CO2 response was shifted to the left, with an increase in hypercapnic drive response, by 0.14 ± 0.16 cm H2O/mm Hg (P = .02), and hypercapnic ventilatory response, by 0.11 ± 0.22 L/min/mm Hg (P = .33). CONCLUSIONS: Patients with obesity-hypoventilation syndrome and higher bicarbonate concentrations had a more blunted CO2 response. Body mass index was not related to CO2 response. Acetazolamide decreased bicarbonate concentration and increased CO2 response.

Loss of cortisol circadian rhythm in patients with traumatic brain injury: a microdialysis evaluation.

BACKGROUND: Traumatic brain injury (TBI) is commonly associated with disturbances of the hypothalamic-pituitary-adrenal axis secretion. Cerebral microdialysis techniques have been recently applied to measure brain interstitial cortisol levels. METHODS: We evaluated for the first time the circadian rhythm of cortisol secretion at 08:00, 16:00, and 24:00 h in the acute phase of TBI by determination of total serum and brain interstitial cortisol levels (microdialysis samples) in 10 patients with TBI. Non-parametric Friedman's two way analysis of variance test was used. RESULTS: Mean age was 29.8 ± 13.6 years. Median Glasgow Coma Scale score after resuscitation was 5 (range 3-10). No differences were found in total serum (P = 0.26) and brain interstitial cortisol (P = 0.77) in the whole sample. Intraindividual analysis showed that circadian variability was lost in all patients, both in serum and brain interstitial cortisol samples in the acute phase after TBI. CONCLUSION: In our series, circadian variability of cortisol evaluated by serum and cerebral microdialysis samples seems to be lost in TBI patients.