Correlation between Thyroid Responses and Inflammatory Cytokines in Critically Ill COVID-19 Patients.

Mechanisms involved in thyroid dysfunction in critically ill coronavirus disease 2019 (COVID-19) patients are not clear. Our objective was to correlate the thyroid response with the pro- and anti-inflammatory cytokines profile in critically ill COVID-19 patients. This was a prospective single-center study. We studied the relationship between continuous variables by using Pearson correlation and simple linear regression. Multiple logistic regression analysis was performed to analyze the factors independently associated with mortality. Seventy-eight patients were included in the study at intensive care unit (ICU) admission and 72 had a measurement of the thyroid and inflammatory profile at day 5. No significant correlations were found between thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) and inflammatory cytokines at ICU admission. At day 5, fT4, was inversely correlated with IL-10 (p = 0.035). IL-10 was associated with maximum lactate (p < 0.001) and SOFA score values (p = 0.012). The multiple logistic regression analysis showed that there was a significant relationship between IL-10 (day 5) and in-hospital mortality after adjusting by age and severity of illness. In conclusion, we found that the thyroid hormone profile and inflammatory cytokines had a weak correlation at ICU admission. Associations of interest between fT4 and IL-10 were found at day 5. IL-10 at day 5 was found to be correlated with low fT4 and markers of organ failure and death.

Concomitant Traumatic Brain Injury and Hemorrhagic Shock: Outcomes Using the Spanish Trauma ICU Registry (RETRAUCI).

BACKGROUND: To compare the main outcomes of trauma patients with and without traumatic brain injury (TBI), hemorrhagic shock, and the combination of both using data from the Spanish trauma intensive care unit (ICU) registry (RETRAUCI). METHODS: Patients admitted to the participating ICUs from March 2015 to May 2019 were included in the study. The main outcomes were analyzed according to the presence of TBI, hemorrhagic shock, and/or both. Comparison of groups with quantitative variables was performed using the Kruskal-Wallis test, and differences between groups with categorical variables were compared using the Chi-square test or Fisher's exact test as appropriate. A P value <.05 was considered significant. RESULTS: Overall, 310 patients (3.98%) were presented with TBI and hemorrhagic shock. Patients with TBI and hemorrhagic shock received more red blood cell (RBC) concentrates, fresh frozen plasma (FFP), a higher ratio FFP/RBC, and had a higher incidence of trauma-induced coagulopathy (60%) (P < .001). These patients had higher mortality (P < .001). Intracranial hypertension was the leading cause of death (50.4%). CONCLUSIONS: Concomitant TBI and hemorrhagic shock occur in nearly 4% of trauma ICU patients. These patients required a higher amount of RBC concentrates and FFP and had an increased mortality.

Risk Factors Associated With Early and Late Posttraumatic Multiorgan Failure: An Analysis From RETRAUCI.

OBJECTIVE: To analyze factors associated with the development of early and late multiorgan failure (MOF) in trauma patients admitted to the intensive care unit (ICU). METHODS: Spanish Trauma ICU Registry (RETRAUCI). Data collected from 52 trauma ICU between March 2015 and December 2019. We analyzed the incidence, outcomes, and the risk factors associated with early (< 72 h) or late (beyond 72 h) MOF in trauma ICU patients. Multiple logistic regression analysis was performed to analyze associated factors. RESULTS: After excluding patients with incomplete data, 9,598 trauma ICU patients constituted the study population. Up to 965 patients (10.1%) presented with MOF, distributed by early MOF in 780 patients (8.1%) and late MOF in 185 patients (1.9%). The multivariate analysis showed that early MOF was associated with: ISS ≥ 16 (OR 2.80), hemodynamic instability (OR from 2.03 to 43.05), trauma-associated coagulopathy (OR 2.32), and acute kidney injury (OR 4.10). Late MOF was associated with: age > 65 years (OR 1.52), hemodynamic instability (OR from 1.92 to 9.94), acute kidney injury (OR 4.22), and nosocomial infection (OR 17.23). MOF was closely related to mortality (crude OR (95% CI) 4.77 (4.22-5.40)). CONCLUSIONS: Multiorgan failure was recorded in 10% of trauma ICU patients, with early MOF being the predominant form. Early and late MOF forms were associated with different risk factors, suggesting different pathophysiological pathways. Early MOF was associated with higher severity of injury and severe bleeding-related complications and late MOF with advanced age and nosocomial infection.

Effects of dexamethasone in traumatic brain injury patients with pericontusional vasogenic edema: A prospective-observational DTI-MRI study.

Cerebral edema is a frequent and serious complication in traumatic brain injury (TBI) patients. The objective is to study the effect of dexamethasone in patients with brain contusions, and to assess its effect on the vasogenic component of the pericontusional edema.Prospective-observational study to quantify, using magnetic resonance imaging, the volume of the edema before and after 10 days of dexamethasone in patients with brain contusions. Using diffusion tensor imaging, we have examined the effect of dexamethasone on fractional anisotropy (FA) and apparent diffusion coefficient (ADC). To assess changes, the pre- and post-treatment values for each patient were compared using a paired-samples Student t test.We included 30 TBI patients, 15 in each group. The volume of the vasogenic edema in the group of patients treated with dexamethasone decreased from 22 to 19 mL and this decrease was statistically significant (P < .05). Nevertheless, in the non-steroids group the volume of the vasogenic edema increased from 11 to 15 mL. There was a significant decrease in the ADC value (from 1.78-1.59; P < .05); and a significant increase in the FA value (0.09-0.11; P < .05) in the patients treated with dexamethasone.Using diffusion tensor imaging we have shown in a selected group of TBI patients with vasogenic pericontusional edema, a reduction of edema volume, a decrease in the ADC and an increase in the FA after treatment with dexamethasone. However, we have no data if such results are beneficial in terms of improving functional outcome.

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.

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.

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.

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.

Prognostic value of the pulmonary dead-space fraction during the early and intermediate phases of acute respiratory distress syndrome.

BACKGROUND: Little is known about the alveolar dead-space fraction after the first week of acute respiratory distress syndrome (ARDS). We measured the dead-space fraction in the early phase (first week) and the intermediate phase (second week) of ARDS, and evaluated the association of dead-space fraction with mortality. METHODS: We prospectively measured dead-space fraction and other variables in 80 intubated patients during the early phase of ARDS and in 49 patients during the intermediate phase. We used multiple logistic regression analysis to evaluate data. The primary outcome was in-hospital mortality. RESULTS: In the early and intermediate phases the dead-space fraction was higher in patients who died than among those who survived (dead-space fraction 0.64 +/- 0.09 vs 0.53 +/- 0.11, P < .001, and 0.62 +/- 0.09 vs 0.50 +/- 0.10, P < .001, respectively). In both the early and intermediate phases the dead-space fraction was independently associated with a greater risk of death. For every dead-space-fraction increase of 0.05 the odds of death increased by 59% in the early phase (odds ratio 1.59, 95% confidence interval 1.18-2.16, P = .003) and by 186% in the intermediate phase (odds ratio 2.87, 95% confidence interval 1.36-6.04, P = .005). Age and Sequential Organ Failure Assessment score were also independently associated with a greater risk of death in both phases. CONCLUSIONS: Increased alveolar dead-space fraction in the early and intermediate phases of ARDS is associated with a greater risk of death.

Expression of toll-like receptors 2 and 4 is upregulated during hospital admission in traumatic patients: lack of correlation with blunted innate immune responses.

BACKGROUND: There are reports with conflicting results on the expression of toll-like receptors (TLRs) in trauma patients. In addition, these studies analyzed TLR expression only at patients' hospital admission but not later when complications usually arise. OBJECTIVES: To analyze the surface expression of TLR2 and TLR4 on circulating monocytes from trauma patients during the hospitalization period and to correlate this with cytokine production after stimulation with TLR2 and TLR4 agonists. The phagocytic capacity of monocytes was analyzed at the same time points of TLR expression analysis; to correlate these molecular findings with the presence or absence of infections. METHODS: Prospective and observational study from June 2005 to June 2007. In all analysis, a control group composed of healthy subjects was included. RESULTS: We studied 70 trauma patients admitted to the intensive care unit (ICU) of a tertiary hospital, and 30 healthy volunteers. Blood samples were collected at hospital admission, on day 7 and 14. Forty-four patients (63%) developed at least one episode of infection. Monocytes from trauma patients expressed higher levels of TLR2 and TLR4 than monocytes from control subjects at all time points. Expression of TLR2 and TLR4 in monocytes from those patients who developed any infection was significantly lower than in those patients without infection but still significantly higher than in control subjects. Cellular responses to TLR4 agonist were impaired. Monocytes from traumatic patients phagocytosized less efficiently than monocytes from control subjects. CONCLUSIONS: These results indicate that trauma patients present a dysregulation of the innate immune system that persists during the first 14 days after hospital admission.

Head injury and inverted Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy or "apical ballooning syndrome" is characterized by an acute onset of transient akinesia of the apical portion of the left ventricle accompanied by electrocardiographic changes and minimal myocardial enzymatic release mimicking acute myocardial infarction without significant stenosis on the coronary angiogram. Emotional or physical stress might trigger this reversible form of cardiomyopathy. We describe a case of a 22-year-old woman presenting with an atypical form of Takotsubo cardiomyopathy after severe head injury.

Incidence and outcome of ischemic hepatitis complicating septic shock.

AIM: The specific incidence of ischemic hepatitis in septic shock patients remains unknown. The aim of this study was to evaluate the incidence of ischemic hepatitis in septic shock and its relationship with mortality. METHODS: We retrospectively studied 181 patients with septic shock admitted to the intensive care unit (ICU). We defined ischemic hepatitis as having a value of serum aminotransferases equal to or higher than 1000 IU/L. We recorded the age, sex, comorbidity, site of infection, the Sequential Organ Failure Assessment (SOFA) score on admission to the ICU, maximum SOFA score and inadequate antibiotic therapy. RESULTS: Twenty-five (13.8%) patients developed ischemic hepatitis. In-hospital mortality was 57% (103 patients). In the ischemic hepatitis group, mortality increased up to 84.0% (21 patients) compared with 52.6% (82 patients) in patients without ischemic hepatitis (control group) (odds ratio [OR]: 4.7; 95% confidence interval [CI]: 1.6-14.4; P = 0.003). The development of ischemic hepatitis, age, maximum SOFA score and inadequate antibiotic therapy were independently associated with an increased risk of death. The odds of death increased by 247% in ischemic hepatitis (OR: 3.47; 95% CI: 1.02-11.8; P = 0.047). CONCLUSION: Ischemic hepatitis is a common complication in septic shock patients, associated with a high mortality.

Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial.

INTRODUCTION: Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment. METHODS: This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation < or = 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines. RESULTS: A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis--undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital--thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection. CONCLUSIONS: Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups. TRIAL REGISTRATION: (Trial registration: US Clinical Trials registry NCT00622570.).

Acute Hypothalamic-pituitary-adrenal response in traumatic brain injury with and without extracerebral trauma.

OBJECTIVE: Endocrine disturbances are common after traumatic brain injury (TBI). Hypothalamic-pituitary-adrenal (HPA) axis response in TBI patients may be related with hemodynamic status. However, its relationship with outcome is unclear. Our objective was to evaluate HPA axis response in the acute phase after TBI in patients with or without extracerebral trauma (ECT), and to investigate the impact of systemic injury and the mechanisms underlying HPA response. METHODS: We prospectively studied 165 patients with moderate to severe TBI. Between 24 and 48 h after TBI, blood samples were taken for plasma adrenocorticotrophin hormone (ACTH) and baseline cortisol measurements. Afterwards, a short corticotrophin hormone test (250 mug Synacthen) was performed and samples were obtained at 30 and 60 min. We compared HPA response in TBI patients presenting with and without ECT and investigate potential mechanisms underlying this response. RESULTS: One hundred and eight patients presented with isolated TBI, whereas 57 patients presented associated ECT. Both groups were comparable. Overall, 23.6% of patients fulfilled adrenal insufficiency (AI) criteria. Patients with plasma ACTH <9 pg/ml and patients presenting with hemorrhagic shock were more likely to present adrenal impairment. Variables associated with mortality were Injury Severity Score, Glasgow Coma Scale, Traumatic Coma Data Bank classification different than type II, need of second level measures to control intracranial pressure and plasma ACTH >9 pg/ml. CONCLUSION: Patients with TBI presenting with or without associated ECT present similar acute HPA response. AI is present in 23.6% of patients. Risk is increased in patients with low plasma ACTH levels and in patients with hemorrhagic shock. Both primary and secondary mechanisms of HPA failure were found. However, AI did not affect outcome.