ß-Blockers for traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) and catecholamine surge, which are associated with poor outcome, may be triggered by traumatic brain injury (TBI).ß Adrenergic receptor blockers (ß-blockers), as potential therapeutic agents to prevent paroxysmal sympathetic hyperactivity and catecholamine surge, have been shown to improve survival after TBI. The principal aim of this study was to investigate the effect of ß-blockers on outcomes in patients with TBI. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane Library databases from inception to September 25, 2020, for randomized controlled trials, nonrandomized controlled trials, and observational studies reporting the effect of ß-blockers on the following outcomes after TBI: mortality, functional measures, and cardiopulmonary adverse effects of ß-blockers (e.g., hypotension, bradycardia, and bronchospasm). With use of random-effects model, we calculated pooled estimates, confidence intervals (CIs), and odds ratios (ORs) of all outcomes. RESULTS: Fifteen studies with 12,721 patients were included. Exposure to ß-blockers after TBI was associated with a significant reduction in adjusted in-hospital mortality (OR, 0.39; 95% CI, 0.30-0.51; I2 = 66.3%; p < 0.001). ß-Blockers significantly improved the long-term (≥6 months) functional outcome (OR, 1.75; 95% CI, 1.09-2.80; I2 = 0%; p = 0.02). Statistically significant difference was not seen for cardiopulmonary adverse events (OR, 0.91; 95% CI, 0.55-1.50; I2 = 25.9%; p = 0.702). CONCLUSION: This meta-analysis demonstrated that administration of ß-blockers after TBI was safe and effective. Administration of ß-blockers may therefore be suggested in the TBI care. However, more high-quality trials are needed to investigate the use of ß-blockers in the management of TBI. LEVEL OF EVIDENCE: Systematic review and meta-analysis, level III.

Cardiovascular autonomic neuropathy in type 2 diabetic patients

SUMMARY Diabetes is one of the most common chronic pathologies around the world, involving treatment with general clinicians, endocrinologists, cardiologists, ophthalmologists, nephrologists and a multidisciplinary team. Patients with type 2 Diabetes Mellitus (T2DM) can be affected by cardiac autonomic neuropathy, leading to increased mortality and morbidity. In this review, we will present current concepts, clinical features, diagnosis, prognosis, and possible treatment. New drugs recently developed to reduce glycemic level presented a pleiotropic effect of reducing sudden death, suggesting a potential use in patients at risk.

RESUMO Diabetes é uma das mais frequentes patologias crônicas em todo o mundo, cujo tratamento envolve uma equipe multidisciplinar, médicos generalistas, endocrinologistas, cardiologistas, nefrologistas e oftalmologistas. Pacientes com diabetes mellitus tipo 2 (DMT2) podem apresentar neuropatia autonômica cardíaca (NAC), levando a aumento de mortalidade e morbidade. Nesta revisão, apresentaremos atuais conceitos, características clínicas, diagnóstico, prognóstico e possíveis tratamentos. Novas drogas recentemente desenvolvidas para redução de níveis glicêmicos apresentaram efeito pleiotrópico de redução de morte súbita, sugerindo um potencial uso neste perfil de pacientes.

Synergic Impact of Vascular Calcification and Low Autonomic Tone in Mortality of Hemodialysis Patients.

BACKGROUND: Both cardiovascular calcification and autonomic dysfunction are frequently encountered in hemodialysis patients. We aimed to investigate the relationship between cardiovascular calcification and heart rate variability (HRV) and their influence on long-term outcome. METHODS: Seventy-eight hemodialysis patients underwent echocardiogram and radiography of the pelvis and hands to identify valvular and vascular calcification. HRV was evaluated using a commercial machine. RESULTS: Based on the average, the patients were divided into higher and lower subgroups of high frequency (HF) and low frequency (LF) respectively. Patients with higher LF were younger and were found to have a lower proportion of diabetes. Their hemoglobin, albumin, and bone morphogenic protein (BMP)-7 levels were significantly higher and both high-sensitive C-reactive protein (hs-CRP) and osteoprotegerin levels were lower (all p < 0.05). In patients of the higher HF group, the proportion of diabetes was lower but they were found to have higher levels of BMP-7 and lower levels of hs-CRP, interleukin-6 (all p < 0.05). Significantly higher LF and HF were noted in patients without vascular calcification, but only hand artery (HA) calcification was negatively correlated with both LF and HF in multivariate analysis. Low LF and high hs-CRP were the independent predictors of mortality. Coexistence of low LF band and HA calcification was associated with the worse outcome. CONCLUSIONS: Abnormal autonomic nervous function was closely related to inflammation and mortality in hemodialysis patients. Calcification of HA was associated with autonomic dysfunction and patients with lower autonomic tone and HA calcification had the highest mortality rate in this population.

Assessment of late anthracycline-induced cardiotoxicity by 123I-mIBG cardiac scintigraphy in patients treated during childhood and adolescence.

PURPOSE: The goal of this study was to evaluate late cardiotoxic effects of anthracyclines (ATC) by evaluating cardiac sympathetic activity in a cohort of asymptomatic patients previously treated with ATC for childhood cancers. METHODS: We studied 89 asymptomatic patients previously treated with ATC with a normal echocardiogram (49 men and 40 women) and a control group of 40 healthy individuals (26 men and 14 women). Both groups underwent planar myocardial 123I-meta-iodobenzylguanidine scintigraphy (123I-mIBG). From these images, the early and late heart-to-mediastinum (H/M) ratio and washout rate (WR) were assessed. RESULTS: The mean survival at the time of the 123I-mIBG scintigraphy was 5.3 ± 3.4 years. Patients treated with ATC had a lower but clinical normal left ventricular ejection fraction (LVEF) compared to controls (60.44 ± 6.5 vs 64.1 ± 6.0%, P < 0.01). Both the late H/M ratio and WR were not able to discriminate ATC treated patients from controls. The cumulative ATC dose was the only independent predictor of the LVEF, explaining approximately 12% of the variation in LVEF (P = 0.01). CONCLUSIONS: Although the pathophysiology behind ATC cardiotoxicity is most likely multifactorial, myocardial sympathetic activity is not associated with a reduction in LVEF 5-years after completion of chemotherapy.

Autonomic Imbalance as a Predictor of Metabolic Risks, Cardiovascular Disease, Diabetes, and Mortality.

CONTEXT: Identifying novel early predictors of metabolic disorders is essential to improving effective primary prevention. OBJECTIVES: The objectives were to examine the contribution of two measures of autonomic imbalance, resting heart rate (RHR) and heart rate variability (HRV), on the development of five metabolic risk outcomes, and on cardiovascular disease, diabetes, and early mortality. DESIGN: This study was a secondary analysis of prospective data from Offspring Cohort participants (N = 1882) in the Framingham Heart Study (FHS). PARTICIPANTS: Participants at FHS Exam 3 (1983-1987) with 1) age years 18 or older, and 2) data on RHR, HRV, and five measures of metabolic risk (blood pressure, fasting glucose, triglycerides, high-density lipoprotein [HDL] cholesterol, and body mass index [BMI]) at three follow-up visits over 12 years. We conducted a backward elimination variable selection procedure on a logistic regression model, using baseline RHR, HRV, age, sex, and smoking status to predict the odds of developing a specific metabolic risk. OUTCOMES: Measures included hyperglycemia, high blood pressure, high triglycerides, low HDL cholesterol, and high BMI over 12 years; incident diabetes, cardiovascular disease, and early mortality over 20 years. RESULTS: RHR and HRV, along with sex, age, and smoking were significant predictors of high blood pressure, hyperglycemia, and a diagnosis of diabetes within 12 years. RHR and HRV also predicted the development of cardiovascular disease and early mortality for most of the sample. CONCLUSIONS: In this community sample two measures of autonomic imbalance predicted multiple poor metabolic outcomes and mortality, making autonomic imbalance a potentially worthy target for intervention studies to reduce risks for cardiovascular disorders, diabetes, and early death.

Asociación de la neuropatía autonómica cardiovascular y el intervalo QT prolongado con la morbimortalidad cardiovascular en pacientes con diabetes mellitus tipo 2 / Association of cardiovascular autonomic neuropathy and prolonged QT interval with cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus

Con el objetivo de evaluar la relación entre la neuropatía autonómica cardiovascular (NACV) y el intervalo QT corregido (QTc) con la morbimortalidad cardiovascular en pacientes con diabetes mellitus tipo 2, se realizó el seguimiento a 5 años de 67 pacientes que acudieron a consulta externa del Servicio de Endocrinología. Se presentaron eventos cardiovasculares en 16 pacientes; el 82 por ciento completó el seguimiento y se encontró que el intervalo QTc prolongado fue la única variable que se asoció de forma significativa a morbimortalidad cardiovascular en el análisis de regresión logística múltiple (RR: 13,56; IC 95 por ciento: 2,01-91,36) (p=0,0074).

In order to evaluate the relationship between cardiovascular autonomic neuropathy and corrected QT interval (QTc) with cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus, we followed up for 5 years 67 patients attending the outpatient Endocrinology Service. 82 percent completed follow-up and cardiovascular events occurred in 16 patients. We found that long QTc interval was the only variable significantly associated with cardiovascular morbidity and mortality in the multiple logistic regression analysis (RR: 13.56, 95 percent CI: 2.01-91.36) (p = 0.0074).

Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators.

CONTEXT: Pheochromocytomas and sympathetic paragangliomas are rare neuroendocrine tumors for which no precise histological or molecular markers have been identified to differentiate benign from malignant tumors. OBJECTIVE: The aim was to determine whether primary tumor location and size are associated with malignancy and decreased survival. DESIGN AND SETTING: We performed a retrospective chart review of patients with either pheochromocytoma or sympathetic paraganglioma. PATIENTS: The study group comprised 371 patients. MAIN OUTCOME MEASURES: Overall survival and disease-specific survival were analyzed according to tumor size and location. RESULTS: Sixty percent of patients with sympathetic paragangliomas and 25% of patients with pheochromocytomas had metastatic disease. Metastasis was more commonly associated with primary tumors located in the mediastinum (69%) and the infradiaphragmatic paraaortic area, including the organ of Zuckerkandl (66%). The primary tumor was larger in patients with metastases than in patients without metastatic disease (P < 0.0001). Patients with sympathetic paragangliomas had a shorter overall survival than patients with pheochromocytomas (P < 0.0001); increased tumor size was associated with shorter overall survival (P < 0.001). Patients with sympathetic paragangliomas were twice as likely to die of disease than patients with pheochromocytomas (hazard ratio = 1.93; 95% confidence interval = 1.20-3.12; P = 0.007). As per multivariate analysis, the location of the primary tumor was a stronger predictor of metastases than was the size of the primary tumor. CONCLUSIONS: The size and location of the primary tumor were significant clinical risk factors for metastasis and decreased overall survival duration. These findings delineate the follow-up and treatment for these tumors.

Association between cardiovascular autonomic functions and time to death in patients with terminal hepatocellular carcinoma.

CONTEXT: A better time-to-death (TTD) prediction can facilitate decision-making processes related to plans for providing effective end-of-life care for patients in hospice wards. OBJECTIVE: To explore the association of cardiovascular autonomic functions with TTD in patients with terminal hepatocellular carcinoma. METHODS: A prospective study was conducted with 33 patients with hepatocellular carcinoma recruited from the hospice ward of a regional hospital in Chiayi county, Taiwan. Serum creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, blood urea nitrogen (BUN), and serum albumin were measured on the admission day. Cardiovascular autonomic functions were evaluated by frequency-domain measures of heart rate variability (HRV) on admission. RESULTS: TTD was significantly associated with total spectrum power (TP) (r=0.55, P=0.001) and high frequency (HF power) (r=0.44, P=0.010) of HRV measurement. The accuracy of within-one-week TTD prediction was 67% for TP and HF power. The accuracy of within-two-week TTD prediction was 82% for TP and 73% for HF. In addition, TTD of the patients was also significantly associated with serum creatinine (r=-0.42, P=0.015), serum albumin (r=-0.46, P=0.007), and BUN (r=-0.44, P=0.010). CONCLUSION: This is the first study to evaluate the association between cardiovascular autonomic functions and TTD in patients with terminal hepatocellular carcinoma. The inclusion of HRV measurement in prognostic models may improve accuracy in TTD prediction and, hence, facilitate medical decision making in hospice care.

Stroke location and association with fatal cardiac outcomes: Northern Manhattan Study (NOMAS).

BACKGROUND AND PURPOSE: Cardiac mortality after stroke is common, and small studies have suggested an association of short-term cardiac mortality with insular location of cerebral infarction. Few population-based studies with long-term follow-up have evaluated the effect of stroke location on the long-term risk of cardiac death or myocardial infarction (MI) after first ischemic stroke. We sought to determine the association between stroke location and cardiac death or MI in a multiethnic community-based cohort. METHODS: The Northern Manhattan Study is a population-based study designed to determine stroke incidence, risk factors, and prognosis in a multiethnic urban population. First ischemic stroke patients age 40 or older were prospectively followed up for cardiac death defined as fatal MI, fatal congestive heart failure, or sudden death/arrhythmia and for nonfatal MI. Primary brain anatomic site was determined by consensus of research neurologists. Hazard ratios (HRs) and 95% CIs were calculated by Cox proportional-hazards models and adjusted for vascular risk factors (age, sex, history of coronary disease, hypertension, diabetes, cholesterol, and smoking), stroke severity, infarct size, and stroke etiology. RESULTS: The study population consisted of 655 patients whose mean age was 69.7+/-12.7 years; 44.6% were men and 51.3% were Hispanic. During a median follow-up of 4.0 years, 44 patients (6.7%) had fatal cardiac events. Of these, fatal MI occurred in 38.6%, fatal congestive heart failure in 18.2%, and sudden death in 43.2%. In multivariate models, clinical diagnosis of left parietal lobe infarction was associated with cardiac death (adjusted HR=4.45; 95% CI, 1.83 to 10.83) and cardiac death or MI (adjusted HR=3.30; 95% CI, 1.45 to 7.51). When analysis of anatomic location was restricted to neuroimaging (computed tomography, magnetic resonance imaging, or both [n=447]), left parietal lobe infarction was associated with cardiac death (adjusted HR=3.37; 95% CI, 1.26 to 8.97), and both left (adjusted HR=3.49; 95% CI, 1.38 to 8.80) and right (adjusted HR=3.13; 95% CI, 1.04 to 9.45) parietal lobe infarctions were associated with cardiac death or MI. We did not find an association between frontal, temporal, or insular stroke and fatal cardiac events, although the number of purely insular strokes was small. CONCLUSIONS: Parietal lobe infarction is an independent predictor of long-term cardiac death or MI in this population. Further studies are needed to confirm whether parietal lobe infarction is an independent predictor of cardiac events and death. Surveillance for cardiac disease and implementation of cardioprotective therapies may reduce cardiac mortality in patients with parietal stroke.

Neuropatia autonômica cardiovascular diabética: fatores de risco, impacto clínico e diagnóstico precoce / Diabetic cardiovascular autonomic neuropathy: risk factors, clinical impact and early diagnosis

A neuropatia autonômica cardiovascular (NAC) constitui uma das complicações de maior repercussão clínica do diabete melito (DM) e, ao mesmo tempo, está entre as menos diagnosticadas. Nesta revisão, são discutidos os principais fatores de risco para o desenvolvimento e a progressão da NAC nos pacientes com DM, a história natural da neuropatia autonômica e seu impacto na doença cardiovascular do DM, bem como os testes para o diagnóstico precoce e o estadiamento da NAC na prática clínica. A pesquisa bibliográfica teve como base dois bancos de dados: Medline e Tripdatabase, com os seguintes descritores: diabetic cardiovascular autonomic neuropathy e cardiovascular autonomic neuropathy and diabetes. Os artigos de 1998 a 2007 em inglês e alemão foram selecionados. A NAC em estágios iniciais (precoce e intermediária) pode ser diagnosticada e revertida, porém, nos casos avançados (estágio grave), resta apenas o tratamento sintomático. A NAC está associada a um maior índice de morbidade e mortalidade cardiovasculares e pior qualidade de vida nos indivíduos diabéticos

Cardiovascular autonomic neuropathy (CAN) is one of the most clinically significant complications of diabetes mellitus (DM), but one of the least frequently diagnosed. In this review, we discuss the major risk factors for the development and progression of CAN in patients with DM, the natural history of autonomic neuropathy and its impact on cardiovascular disease in DM, as well as the tests for the early diagnosis and staging of CAN in the clinical practice. The bibliographic research was based on two databases: Medline and Tripdatabase, with the following descriptors: diabetic cardiovascular autonomic neuropathy and cardiovascular autonomic neuropathy and diabetes. We selected English and German articles, written between 1998 and 2007. In its initial stages (early and intermediate), CAN may be diagnosed and reversed. However, in advanced cases (severe stage), the only treatment that remains is a symptomatic one. CAN is associated with higher cardiovascular morbidity and mortality rates and poor quality of life in diabetic individuals.

Feline dysautonomia in the Midwestern United States: a retrospective study of nine cases.

Dysautonomia of domestic animals is pathologically characterized by chromatolytic degeneration of the neurons in the autonomic nervous ganglia that results in clinical signs related to dysfunction or failure of the sympathetic and parasympathetic nervous systems. The exact cause is unknown. It has a poor prognosis among all species reported and no definitive treatment is available currently. To date, most reported feline cases have occurred in the United Kingdom and Scandinavia. The cases reported here highlight the clinical signs, physical examination findings, and results of autonomic nervous system function testing in nine cats with dysautonomia in the US. Feline dysautonomia is uncommon in the US, but may have a regional prevalence, as is seen in dogs with most cases reported in Missouri and Kansas.

Preoperative heart rate variability in relation to surgery outcome in refractory epilepsy.

BACKGROUND: Epilepsy patients may have an impaired autonomic cardiac control, which has been associated with an increased incidence of sudden unexpected death among people with epilepsy (SUDEP). The risk of SUDEP is particularly high among epilepsy surgery candidates with refractory epilepsy. This risk seems to be reduced after successful surgery but whether this is an effect of surgery or reflects pre-existing differences between good and poor responders is under debate. METHODS: We used spectral analysis to analyze prospectively heart rate variability (HRV) preoperatively in 21 consecutive patients with temporal lobe epilepsy who were planned for epilepsy surgery. The presurgical HRV based on ambulatory 24 hours EKG recordings was analyzed in relation to seizure control at 1 year after surgery. RESULTS: Patients had significantly lower SD of RR-intervals, total power, very low frequency power and low frequency power than matched healthy controls. Patients with good outcome of surgery (Engel class I; n = 11) did not differ from their controls while those with poor outcome (Engel class II-IV; n = 10) had significantly lower power in all domains than those with a favorable outcome. CONCLUSIONS: Measurements of heart rate variability preoperatively indicate that patients with a poor outcome of surgery have a more pronounced impairment of sympathetic as well as parasympathetic cardiac control than those with good outcome. Reduced heart rate variability may be associated with an increased risk of sudden unexpected death among people with epilepsy (SUDEP). Good surgery candidates may a priori have a lower risk of SUDEP.

Lack of circadian variation in the activity of the autonomic nervous system after major abdominal operations.

OBJECTIVE: Most sudden postoperative deaths occur during the night and we conjectured that this was associated with circadian variations in the autonomic nervous tone, reflected in heart rate variability. DESIGN: Prospective clinical study. SETTINGS: University hospital, Denmark. SUBJECTS: 44 patients who had had major abdominal operations. INTERVENTIONS: Patients were monitored with 24-hour Holter ECG on the second postoperative day-evening-night. We calculated heart rate variability from the standard deviation of all normal R-R intervals (excluding ectopics-NN intervals) around the mean NN interval for the period of measurement (SDNN), the root mean square of the standard deviation of the differences between NN intervals (RMSSD), the percentage of NN intervals differing by more than 50 msec from adjacent NN intervals (pNN50) and the coefficient of component variance (meanNN/SDNN). MAIN OUTCOME MEASURES: Heart rate and heart rate variability. RESULTS: Circadian variation calculated from the SDNN (p = 0.43) the pNN50 (p = 0.11), the RMSSD (p = 0.47), and mean NN:SDNN ratio (p = 0.13) was absent postoperatively. Circadian variation in the heart rate was present but was set on a higher level compared with reference values. CONCLUSION: After major abdominal operations there was a lack of circadian variation in the autonomic nervous tone.

[Cardiac autonomic tone in risk stratification after myocardial infarct: results of a prospective long-term study of 411 consecutive patients]. / Kardialer autonomer Tonus zur Risikostratifikation nach Myokardinfarkt: Ergebnisse einer prospektiven Langzeit-Studie bei 411 knosekutiven Patienten.

Prognosis of patients surviving acute myocardial infarction has substantially improved over the last two decades. However, stratification of patients at risk for death due to arrhythmic events remains a clinical challenge. Due to the important role of the autonomic nervous system in the genesis of sudden death, autonomic markers such as heart rate variability and baroreflex sensitivity have recently gained attention as risk stratification parameters. The present study reports the results of noninvasive risk stratification in 411 consecutive postinfarction patients treated due to contemporary therapeutical guidelines with a high proportion of patients discharged with a patent infarct related artery. The diagnostic arsenal of risk parameters comprised heart rate variability, baroreflex sensitivity, and more traditional markers such as non-sustained ventricular tachycardia, left ventricular ejection fraction, and ventricular late potentials. Patients were followed for a mean of 33 +/- 21 months. Stepwise logistic regression analysis revealed that left ventricular function, both autonomic markers, and the patency of the infarct related artery were independent predictors of the prospectively defined primary study endpoint, i.e., all-cause mortality plus ventricular tachyarrhythmic events. With respect to the secondary endpoint (ventricular tachyarrhythmic events), left ventricular function, heart rate variability, and infarct vessel patency were independent predictors. Ventricular late potentials and nonsustained ventricular tachycardia had no predictive value with respect to ventricular tachyarrhythmic events. These findings from a large prospective long-term study demonstrate the value of markers of cardiac autonomic tone in identifying infarct survivors at risk for malignant ventricular tachyarrhythmias and sudden death.

Oxigenación tisular durante la crisis de disautonomía en el tétano severo / Tissular oxygenation during the crisis of dysautonomia in to severe tetanus

El síndrome de hiperactividad simpática en el marco del tétanos severo, es un cuadro de gravedad extrema por ya ser una de las principales causas de muerte. Fisiopatológicamente continúa siendo un "misterio", tratáse de explicar todo lo que ocurre debido a la elevada concentración de catecolaminas circulantes. Sin embargo, poco se sabe sobre el comportamiento de la oxigenación de los tejidos durante las crisis disautonómicas, dada las dificultades que existen para su diagnóstico, detección precoz y ausencia de literatura al respecto. Por tal motivo nos propusimos evaluar en forma prospectiva los pacientes con tétanos severo sometidos a monitoreo hemodinámico invasivo y de la perfusión del territorio esplácnico, particularmente durante los episodios de sobreactividad del sistema nervioso autónomo. Así, durante 20 crisis disautonómicas desarrolladas en 12 pacientes consecutivos se evidenció una profunda depresión miocárdica e hipoxia tisular, los que pueden constituir factores de riesgo clave que ayuden a explicar la elevada morbimortalidad cuando el síndrome hace su aparición en el marco del tétanos severo

Estudio del diagnostico clinico patologico en autopsias del hospital de clinicas de la ciudad de La Paz (Bolivia) / Clinic and patological diagnostic study in autopsies at clinics hospital in La Paz city (Bolivia)

Este es un estudio retrospectivo cuyo objetivo principal es valorar la concordancia entre el diagnostico principal y los hallazgos patologicos de las autopsias de los pacientes fallecidos en el HOSPITAL DE CLINICAS UNIVERSITARIO. Se revisaron los diagnosticos clinicos de autopsias de los casos de estudio postmortem realizados entre el 1ro. de enero de 1975 y el 31 de Abril de 1990, en el Servicio de Anatomia Patologica del Hospital de Clinicas. Estas autopsias se realizaron en 4498 defunciones en el mismo periodo de tiempo constituyendo el 20.5 por ciento . En cada caso particular, se comparo el diagnostico clinico con el diagnostico principal de la autopsia para ver si el 1ro. se confirmaba o no, que pudo hacerse solo en 926 casoso auotpsiados. En 40 autopsias no existia el diagnostico clinico en la solicitud de autopsia, o la autopsia se realizo en pacientes que tuvieron menos de 24 horas en el Hospital, lo que impidio un estudio adecuado en relacion al diagnostico, motivo por el cual este grupo no ingreso al estudio. Encontrandose un grado de concordacia en 60.7 por ciento a mayor tiempo de estancia en el hospital, se observo un leve aumento de la concordancia de los diagnosticos