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.

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.

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.

Glutamine as a modulator of the immune system of critical care patients: effect on Toll-like receptor expression. A preliminary study.

OBJECTIVE: We evaluated the expression of Toll-like receptors 2 and 4 (TLR-2 and TLR-4) in circulating monocytes from peripheral blood of critical care patients treated with and without glutamine. Because no research has been published to date on the effect of glutamine on TLR receptors in critical patients, it was determined in an initial sample of 30 patients. METHODS: This was a prospective, randomized, single-blind study with 15 patients assigned to receive parenteral nutrition with a daily glutamine supplement of 0.35 g/kg. The control group received isocaloric-isonitrogenous parenteral nutrition. Blood samples were extracted before beginning the treatment and at 5 and 14 d. Expressions of CD14, TLR-2, and TLR-4 were determined by flow cytometry. Levels of TLRs were expressed as mean fluorescence intensity (mfi). RESULTS: Basal characteristics were similar in both groups. The expressions of TLR-2 in the treatment group with glutamine were 4.67 +/- 3.82 mfi before treatment, 3.91 +/- 2.04 mfi at 5 d, and 4.28 +/- 2.47 mfi at 14 d. The expressions of TLR-2 in the control group were 5.49 +/- 3.20 mfi before treatment, 4.48 +/- 2.15 mfi at 5 d, and 4.36 +/- 2.36 mfi at 14 d. The expressions of TLR-4 in the treatment group were 1.65 +/- 1.89 mfi before treatment, 1.23 +/- 1.10 mfi at 5 d, and 1.77 +/- 1.97 at 14 d. The expressions of TLR-4 in the control group were 1.51 +/- 1.76 mfi before treatment, 1.36 +/- 0.99 mfi at 5 d, and 1.26 +/- 0.59 mfi at 14 d. Infections were detected in 11 patients who received glutamine and 13 control patients (P = 0.51). CONCLUSION: In critical care patients, parenteral nutrition supplemented with glutamine does not increase the expression of TLR-2 or TLR-4 in peripheral blood monocytes.

Resting energy expenditure during mechanical ventilation and its relationship with the type of lesion.

BACKGROUND: Resting energy expenditure (REE) of critically ill patients is usually calculated according to basal energy expenditure obtained from Harris-Benedict equations traditionally corrected by different stress factors, resulting in a variable accuracy for the individual patient. The objective of this study was to investigate whether or not the type of lesion affects the metabolism level of critically ill patients treated with mechanical ventilation. We performed a retrospective study measuring the REE of critically ill patients with 3 different types of lesions (trauma, medical, surgical) who were treated with mechanical ventilation and sedation. Each lesion group of patients was matched with another group, differing in the type of lesion, according to gender, age, and weight. METHODS: Eighty-seven from a database of 175 critically ill patients undergoing indirect calorimetry were necessary for matching. Twenty matched pairs of patients for each of the following different type of lesion were obtained: medical vs surgical, medical vs trauma, and surgical vs trauma. RESULTS: The mean REE difference was 52 kcal/d (95% confidence interval [CI] of -136 -241 kcal/d) for the medical vs surgical group, 5 kcal/d (95% CI -236 -247 kcal/d) for the medical vs trauma group and 43 kcal/d (95% CI of -132-219 kcal/d) for the surgical vs trauma group. No statistically significant differences between groups were found in the measured REE. We did not find statistically significant differences in the measured REE of patients with and without infection. CONCLUSIONS: Critically ill patients with different types of lesion treated with mechanical ventilation have similar measured REE.

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.

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.

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.

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.

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)