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.

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.

Low-dose steroid therapy does not affect hemodynamic response in septic shock patients.

PURPOSE: Several studies showed that low-dose steroid therapy (LDST) in patients with septic shock leads to a significantly shorter duration of shock and a decreased mortality. However, these results have been criticized. Our purpose was to evaluate the effects of LDST on time to shock reversal and mortality in septic shock. MATERIALS AND METHODS: We retrospectively studied 203 patients with septic shock admitted to the intensive care unit of our tertiary hospital. A short corticotropin test was performed in all patients within 72 hours of septic shock onset. We performed a propensity score analysis through a logistic regression model with baseline relevant characteristics, and evaluated the influence of LDST on time to shock reversal and inhospital mortality. RESULTS: One hundred twenty-four patients were treated with LDST (steroid group) and 79 without LDST (control group). Patients treated with steroids presented higher Simplified Acute Physiology Score II and maximum Sepsis-Related Organ Failure Assessment scores. Both groups presented similar baseline and stimulated cortisol values. The hazard ratio of remaining on shock adjusted by severity of illness, inadequate antibiotic, and propensity score was 1.15 (95% confidence interval 0.71-1.86) for patients treated with steroids. Inhospital mortality was 62% in the steroid group and 52% in the control group (P = .84). Logistic regression analysis with propensity score neither showed differences between steroid and control group in the inhospital mortality. Predictors of inhospital mortality were age, maximum Sepsis-Related Organ Failure Assessment score, and inadequate antibiotics. CONCLUSION: In our study, treatment with low-dose steroid therapy was not associated to a reduction in time to shock reversal or mortality.

Relationship between plasma adrenocorticotropin hormone and intensive care unit survival in early traumatic brain injury.

BACKGROUND: Hypothalamic pituitary adrenal response has been recently evaluated in patients with traumatic brain injury (TBI) with different results. Our objective was to study this response and its relationship with outcome in the early stage after TBI. METHODS: We conducted a prospective observational clinical study in the intensive care unit of a tertiary level university hospital. The study included 50 consecutive patients who suffered isolated TBI. Intracranial pressure (ICP) was measured by an intraparenchymal probe. All patients were sedated and mechanically ventilated. Second-level measures were provided as per protocol, when needed. We measured plasma adrenocorticotropin hormone (ACTH) levels, as well as baseline and stimulated serum cortisol after a high-dose corticotrophin stimulation test, within 2 days after TBI for all patients. RESULTS: Mean age was 36 +/- 18 (range 16-77) years. Forty-four (88%) were male. Median Glasgow Coma Scale score was 7. Mean ACTH was 15.4 +/- 19.8 pg/mL. Mean baseline cortisol was 14.8 +/- 9.0 microg/dL and mean stimulated cortisol was 27.1 +/- 7.3 microg/dL and 30.5 +/- 7.2 microg/dL at 30 and 60 minutes, respectively. Baseline and stimulated cortisol were not correlated with mortality. Logistic regression analysis revealed that, either plasma ACTH levels <9 pg/mL or lack of indication to provide second-level measures to control ICP were significant independent predictors of survival. CONCLUSIONS: The presence of a low plasma ACTH concentration at an early stage of TBI and lack of indication to provide second-level measures to control ICP were associated with a higher intensive care unit survival.

[Hospital resources and myocardial infarction case fatality. The IBERICA study]. / Recursos hospitalarios y letalidad por infarto de miocardio. Estudio IBERICA.

INTRODUCTION AND OBJECTIVES: To determine the proportion of patients with myocardial infarction (MI) not admitted to a coronary care unit (CCU), the variables associated with admission into a CCU, and whether admission to a CCU, and the availability of coronary angiography in the same hospital, were associated with 28-day case fatality. PATIENTS AND METHOD: Population-based registry of MI in patients 25 to 74 years of age, admitted during 1996-1998. Demographic and clinical characteristics were recorded, as well as management, clinical course and survival after 28 days. Hospitals were classified according to the availability of a CCU and catheterization laboratory (advanced hospital), CCU only (intermediate hospital) or neither (basic hospital). Admission to the CCU was also recorded. RESULTS: In all, 9046 cases of MI were recorded; in 11.3% the patient was not admitted to a CCU. Age, smoking (OR=1.33; 95% CI, 1.08-1.64), non-Q MI (OR=0.62; 95% CI, 0.49-0.78) or undetermined location of MI (OR=0.34; 95% CI, 0.23-0.50), Killip 4 score on admission (OR=0.63; 95% CI, 0.40-1.00) and delay in arrival at the hospital >6 h were associated with CCU admission. Patients admitted to a CCU showed a lower case fatality in the first 24 h (4.2% vs 23.5%), which was independent of comorbidity, severity and treatment. The 24-hour survivors admitted to a basic hospital had higher case fatality (17.3% vs 7.8%) than other groups, which was related to differences in treatment. CONCLUSIONS: CCU admission is associated with a lower case fatality in the first 24 h. Admission to a basic hospital is associated with a higher 28-day case fatality even in patients who survive 24 h.