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1.
Intern Emerg Med ; 18(5): 1521-1532, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36859647

RESUMO

As a prolonged surge scenario, the COVID-19 pandemic has offered an unparalleled opportunity to improve hospital surge capacity (SC) understanding and the ability to manage it. In this study, the authors report the experience of a large hospital network and evaluate potential relationships between Intensive Care Units SC (ICU-SC) and some hospital-related variables: bed occupancy, emergency department admissions, ward admission from ED, and elective surgery procedures. Pearson's partial correlation coefficient (r) has been used to define the relationship between SC and the daily values of the above variables, collected through a dedicated digital platform that also ensured a regular quality check of the data. The observation has concerned several levels of analysis, namely two different types of SC calculation (SC base-SCb and SC actual-SCa), hospital category level and multi-hospital level, and two consecutive pandemic waves. Among the 16 hospitals observed, the correlation was shown to be moderate-positive with non-ICU bed occupancy (r/ = 0.62, r/ = 0.54), strong/moderate with ICU bed occupancy (r/ = 0.72, r/ = 0.54), and moderate with ward admissions from ED (r/ = 0.50, r/ = 0.51) On the contrary, the correlation proved to be moderate-negative with ED admissions (r/ = - 0.69, r/ = - 0.62) and low with the number of elective surgery procedures (r/ = - 0.10, r/ = - 0.16). This study identified a positive correlation between SC and three variables monitored: ICU bed occupancy, non-ICU bed occupancy, and ward admissions from ED. On the contrary, the correlation was negative for ED admission and the number of elective surgery procedures. The results have been confirmed across all levels of analysis adopted.


Assuntos
COVID-19 , Capacidade de Resposta ante Emergências , Humanos , COVID-19/epidemiologia , Pandemias , Cuidados Críticos , Unidades de Terapia Intensiva , Hospitais , Serviço Hospitalar de Emergência , Estudos Retrospectivos
2.
Eur J Emerg Med ; 30(1): 7-14, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35861664

RESUMO

The emergency department (ED) is a high-risk setting for the occurrence of medication discrepancies (MDs) due to inconsistencies between real and documented chronic medication therapies. A clinical pharmacist (CP) improves medication safety by performing a structured medication reconciliation on ED admission. The main objective was to identify the frequency and type of MDs in the chronic medication therapy by comparing the medication displayed in the home medication module of the electronic medical record and in the genereal practitioner's (GP) referral letter with the best possible medication history by performing a structured medication reconciliation on ED admission. This prospective, monocentric, interventional study was carried out in the ED of a tertiary care university hospital in Brussels, Belgium. Inclusion criteria were patients of at least 65 years, polypharmacy, ED admission between 8 a.m. and 4 p.m. on weekdays, hospitalization and signed informed consent. During 24 days, a CP performed a structured medication reconciliation in order to obtain the best possible medication history and registered all MDs. The CP compared the best possible medication history with the home medication module and the GP's referral letter and registered the different types of MDs. Eighty-three patients were included. The median number of medications in the home medication module and the best possible medication history was significantly different {7.0 [interquartile range (IQR), 5.0-11.0] vs. 8.0 (IQR, 6.0-11.0)/patient; P < 0.0001} with a median of 5.0 (IQR, 3.0-8.0) MDs per patient. Main MDs were omission (38.8%), addition (18.4%) and a deviant administration time (15.2%). Only 22.9% of patients ( N = 19) had a GP's referral letter containing their chronic medication therapy. The median number of medications in the GP's referral letter and the best possible medication history were significantly different [6.0 (IQR, 4.0-9.0) vs. 8.0 (IQR, 7.0-11.0)/patient; P < 0.0001] with a median of 6.0 (IQR, 5.0-11.0) MDs per patient. Main MDs were omissions (39.9%), deviant frequencies (35.3%) and doses (16.7%). A CP, integrated in a multidisciplinary ED team, enhances medication safety by intercepting MDs on ED admission. Few patients possess a GP's referral letter containing their chronic medication therapy and when they do, the accuracy and completeness are poor.


Assuntos
Reconciliação de Medicamentos , Farmacêuticos , Humanos , Estudos Prospectivos , Preparações Farmacêuticas , Serviço Hospitalar de Emergência , Admissão do Paciente
3.
Front Public Health ; 10: 916133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003627

RESUMO

Background: There is a need for complete and accurate epidemiological studies for traumatic brain injury (TBI). Secondary use of administrative data can provide country-specific population data across the full spectrum of disease. Aim: This study aims to provide a population-based overview of Belgian TBI hospital admissions as well as their health-related and employment outcomes. Methods: A combined administrative dataset with deterministic linkage at individual level was used to assess all TBI hospitalizations in Belgium during the year 2016. Discharge data were used for patient selection and description of injuries. Claims data represented the health services used by the patient and health-related follow-up beyond hospitalization. Finally, social security data gave insight in changes to employment situation. Results: A total of 17,086 patients with TBI were identified, with falls as the predominant cause of injury. Diffuse intracranial injury was the most common type of TBI and 53% had injuries to other body regions as well. In-hospital mortality was 6%. The median length of hospital stay was 2 days, with 20% being admitted to intensive care and 28% undergoing surgery. After hospitalization, 23% had inpatient rehabilitation. Among adults in the labor force pre-injury, 72% of patients with mild TBI and 59% with moderate-to-severe TBI returned to work within 1 year post-injury. Discussion: Administrative data are a valuable resource for population research. Some limitations need to be considered, however, which can in part be overcome by enrichment of administrative datasets with other data sources such as from trauma registries.


Assuntos
Lesões Encefálicas Traumáticas , Hospitalização , Adulto , Bélgica/epidemiologia , Lesões Encefálicas Traumáticas/epidemiologia , Humanos , Incidência , Tempo de Internação
4.
PLoS One ; 17(5): e0268737, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35609037

RESUMO

BACKGROUND: For more than 150 years, war surgery has been at the heart of the humanitarian assistance offered by the International Committee of the Red Cross (ICRC) in conflict zones around the world. Mental health and psychosocial support (MHPSS) is increasingly recognized as an integral part of the medical care offered to this highly vulnerable group of patients. This study seeks to identify patient characteristics associated with high distress prior to MHPSS and predictors of improvement following it. METHODS: Between October 2018 and April 2020, 2,008 weapon-wounded patients received MHPSS in ICRC-supported hospitals in the Democratic Republic of Congo (DRC), Mali and Nigeria. The 21-item Depression and Anxiety Scale (DASS21), the Impact of Events Scale Revised (IES-R) and the ICRC functionality scale for Africa were administered before and after the MHPSS response. Logistic regression models were used to measure associations between outcome and exposure variables. Data was initially collected for monitoring purposes and analyzed retrospectively for the sake of this study. RESULTS: The main reasons for surgery were firearms (65%), other weapons (13%) and mines (5%). Linear trends were found between increasing number of days between violence and first consultation and decreased likelihood of presenting high levels of anxiety (aOR 0.75, p = 0.014), and stress (aOR 0.78, p = 0.032). Violence committed by military/armed group was associated with increased likelihood of reporting high levels of anxiety (aOR 2.47, p = 0.047). On the IES-R, high scores at baseline were more likely to be found among illiterate patients (aOR 0.08, p = 0.042) and having been wounded by firearms considerably increased the likelihood of reporting high levels of PTSD (aOR 21.34, p = 0.035). Following MHPSS, 92.28% of the patients showed a reduction in symptoms on the DASS21, 93.00% showed a reduction in symptoms on the IES-R and 83.04% showed an improvement on the ICRC Africa functioning scale. On the DASS21, factors negatively associated with improved anxiety included lack of social support (aOR 0.17, p = 0.047) and suffering from a chronic medical/physical condition (aOR 0.40, p = 0.013). Patients with reduced IES-R scores were more likely to have a high level of education (aOR 8.95, p = 0.029) and to have received MHPSS that lasted between 22 and 30 days (aOR 8.73, p = 0.008). Predictors of improved functioning included being 35-44 years of age (aOR 3.74, p = 0.004) and suffering from a severe or chronic medical condition (aOR 1.66, p = 0.044). CONCLUSIONS: Clinical implications of this study include the increased involvement of family and other caregivers in the MHPSS and longer-term follow-up of patients with severe and/or chronic medical conditions. Further research is needed with regard to joint psychological and physical outcomes, the role of the patient's education level and the personal styles and techniques used by the counsellors.


Assuntos
Saúde Mental , Sistemas de Apoio Psicossocial , República Democrática do Congo/epidemiologia , Humanos , Mali/epidemiologia , Nigéria/epidemiologia , Estudos Retrospectivos
5.
Prehosp Disaster Med ; 37(4): 553-557, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35586879

RESUMO

On March 15, 2019, Cyclone Idai made landfall near the port city of Beira in central Mozambique causing significant casualties and serious damage to infrastructure. The Emergency Medical Team Type 2 - Italy Regione Piemonte (EMT2-ITA) was deployed approximately two weeks after the disaster to support the country in need, providing essential medical and surgical care.The EMT2-ITA staff was composed of 77 team members including two rotations and integrating local staff. A total of 1,121 patients (1,183 triage admissions) were treated during the 27 days of field hospital activity; among all the admissions, only few cases (17; 1%) were directly or indirectly attributed to the disaster event. Only three cases of cholera were confirmed and transferred to one of the treatment centers set up in Beira. The EMT2-ITA performed a total of 62 surgical operations (orthopedic, gynecological, general, and plastic surgery), of which more than one-half were elective procedures.The objective of this manuscript is to report the mission of the EMT2-ITA in Mozambique, raising interesting points of discussion regarding the impact of timing on the mission outcomes, the operational and clinical activities in the field hospital, and the great importance to integrate local staff into the team.


Assuntos
Cólera , Tempestades Ciclônicas , Desastres , Humanos , Unidades Móveis de Saúde , Moçambique
6.
Cureus ; 14(2): e22188, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35308713

RESUMO

Background In 2017, Idlib, Syria, was exposed to a chemical attack with sarin gas. Many patients of the attack were presented to the Al Rahman Charity Hospital in northern Syria. The aim of this study is to describe the clinical manifestations of sarin gas exposure, as well as the management and outcome of these manifestations in areas with poor healthcare infrastructure. Methods In a case series study design, medical records of suspected sarin exposed patients were reviewed in terms of age, gender, initial clinical presentation, management, and outcome. Results Seventeen patients with signs of sarin gas exposure had detailed medical records. The mean age was 29.1 years with a range of 4-70 years. Six patients were male (35.3%), and four (23.5%) were children under 18 years. At initial presentation, all victims suffered from respiratory distress because of severe airway inflammation, chest pain, and ophthalmological symptoms. All patients featured varying degrees of intestinal, neurologic, and dermatological signs and symptoms. Acute symptom management consisted of oxygen (100% of patients), atropine (100%), bronchodilators (82.4%), dexamethasone (82.4%), anti-emetics (82.4%), paracetamol (47.1%), and ranitidine (41.2%). Rapid symptomatic recovery was observed in 13 patients (76.5%) who stayed in the hospital for less than 24 hours, but four patients (23.5%) had to be admitted for more than 24 hours. The median length of stay was 22.2 hours (with a range of eight to 48 hours). Two patients required intensive care. Of the studied sample, all patients survived. Interpretation This study demonstrates that even in austere healthcare settings, survival rate and prognosis of sarin gas contaminated patients are fair if basic measures and symptomatic treatment are performed. The study provides insight into the clinical presentation, management, and hospital course likely to result from future sarin gas releases.

7.
BMJ Glob Health ; 6(11)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34844999

RESUMO

INTRODUCTION: Sierra Leone, one of the countries with the highest maternal and perinatal mortality in the world, launched its first National Emergency Medical Service (NEMS) in 2018. We carried out a countrywide assessment to analyse NEMS operational times for obstetric emergencies in respect the access to timely essential surgery within 2 hours. Moreover, we evaluated the relationship between operational times and maternal and perinatal mortality. METHODS: We collected prehospital data of 6387 obstetric emergencies referrals from primary health units to hospital facilities between June 2019 and May 2020 and we estimated the proportion of referrals with a prehospital time (PT) within 2 hours. The association between PT and mortality was investigated using Poisson regression models for binary data. RESULTS: At the national level, the proportion of emergency obstetric referrals with a PT within 2 hours was 58.5% (95% CI 56.9% to 60.1%) during the rainy season and 61.4% (95% CI 59.5% to 63.2%) during the dry season. Results were substantially different between districts, with the capital city of Freetown reporting more than 90% of referrals within the benchmark and some rural districts less than 40%. Risk of maternal death at 60, 120 and 180 min of PT was 1.8%, 3.8% and 4.3%, respectively. Corresponding figures for perinatal mortality were 16%, 18% and 25%. CONCLUSION: NEMS operational times for obstetric emergencies in Sierra Leone vary greatly and referral transports in rural areas struggle to reach essential surgery within 2 hours. Maternal and perinatal risk of death increased concurrently with operational times, even beyond the 2-hour target, therefore, any reduction of the time to reach the hospital, may translate into improved patient outcomes.


Assuntos
Ambulâncias , Serviços Médicos de Emergência , Feminino , Humanos , Gravidez , Encaminhamento e Consulta , População Rural , Serra Leoa/epidemiologia
8.
Cureus ; 13(8): e17522, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34603892

RESUMO

Background In 2014, Hama Governorate was exposed twice to chlorine gas, with 15 patients presenting to Kafr Zita Hospital in Northwest Syria. This study aimed to describe clinical manifestations of chlorine gas exposure to identify factors leading to facility admission and the need for ICU/intubation in conflict-affected areas with limited healthcare infrastructure. Methods We conducted a case-series study, using medical records of suspected chlorine-exposed patients presenting at Kafr Zita Hospital on either 11 April or 22 May 2014. Data on age, sex, initial clinical presentation, therapeutic management, and outcome were compared by hospital admission/non-admission and attack date. All patients provided verbal informed consent. Results Fifteen patients with signs of chlorine gas exposure had detailed medical records. The mean age was 25.7 years (range 2-59), eight were male (53%), and three (20%) were under age 16. At initial presentation, all experienced respiratory distress, due to severe airway inflammation confirmed by nonspecific pulmonary infiltrates on chest x-ray, and similar intestinal, neurological, dermatological, ophthalmological, and psychological signs and symptoms. Acute management consisted of oxygen and bronchodilators for all patients, hydrocortisone (93%), antiemetics (80%), and dexamethasone (13%). Seven (47%) made a rapid symptomatic recovery and were discharged the same day and eight (53%) were admitted for a median of two days (range 1-6 days), one of whom required intubation and later died. The only significant associations found were higher mean pulse rate (i.e. 138 versus 124; p=0.043) and body temperature (37.0 versus 36.5; p=0.019) among admitted patients compared to non-admitted. Conclusion Our results demonstrated that even in low-resource humanitarian settings the survival rate for chlorine gas exposed patients is fair. Despite the small sample, this study provides insight into the clinical presentation, management, and outcomes of weaponized chlorine gas exposure, though further research is required to understand any chronic consequences.

9.
Eur J Trauma Emerg Surg ; 45(1): 39-48, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30542747

RESUMO

PURPOSE: Major trauma remains a significant cause of morbidity and mortality in the developed and developing world. In 2013, nearly 5 million people worldwide died from their injuries, and almost 1 billion individuals sustained injuries that warranted some type of healthcare, accounting for around 10% of the global burden of disease in general. Behind the statistics, severe trauma takes a major toll on individuals, their families and healthcare systems. Management of the patient with severe trauma requires multiple interventions in a highly time-sensitive context and fragmentation of care, characterised by loss of information and time among disciplines, departments and individuals, both outside the hospital and within it, is frequent. Outcomes may be improved by better streamlining of pre- and intra-hospital care. METHODS: We describe the basis for development of a multi-stakeholder consortium by the European Critical Care Foundation working closely with a number of European Scientific Societies to address and overcome problems of fragmentation in the care of patients with severe trauma. RESULT: The consortium will develop and introduce an information management system adapted to severe trauma, which will integrate continuous monitoring of vital parameters and point-of-care diagnostics. The key innovation of the project is to harness the power of information technologies and artificial intelligence to provide computer-enhanced clinical evaluation and decision-support to streamline the multiple points at which information and time are potentially lost. CONCLUSIONS: The severe trauma management platform thus created could have multiple benefits beyond its immediate use in managing the care of injured patients.


Assuntos
Cuidados Críticos/normas , Serviços Médicos de Emergência/normas , Serviço Hospitalar de Emergência/normas , Ferimentos e Lesões/terapia , Eficiência Organizacional , Europa (Continente) , Fundações , Humanos , Modelos Organizacionais , Sistemas Automatizados de Assistência Junto ao Leito , Sociedades Médicas
10.
Disaster Med Public Health Prep ; 10(6): 874-882, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27737721

RESUMO

OBJECTIVE: The Syrian civil war since 2011 has led to one of the most complex humanitarian emergencies in history. The objective of this study was to document the impact of the conflict on the familial, educational, and public health state of Syrian children. METHODS: A cross-sectional observational study was conducted in May 2015. Health care workers visited families with a prospectively designed data sheet in 4 Northern Syrian governorates. RESULTS: The 1001 children included in this study originated from Aleppo (41%), Idleb (36%), Hamah (15%), and Lattakia (8%). The children's median age was 6 years (range, 0-15 years; interquartile range, 3-11 years), and 61% were boys. Almost 20% of the children were internally displaced, and 5% had deceased or missing parents. Children lacked access to safe drinking water (15%), appropriate sanitation (23%), healthy nutrition (16%), and pediatric health care providers (64%). Vaccination was inadequate in 72%. More than half of school-aged children had no access to education. Children in Idleb and Lattakia were at greater risk of having unmet public health needs. Younger children were at greater risk of having an incomplete vaccination state. CONCLUSIONS: After 4 years of civil war in Syria, children have lost parents, live in substandard life quality circumstances, and are at risk for outbreaks because of worsening vaccination states and insufficient availability of health care providers. (Disaster Med Public Health Preparedness. 2016;10:874-882).


Assuntos
Educação/normas , Saúde Pública/normas , Guerra , Adolescente , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Estudos Transversais , Educação/métodos , Educação/estatística & dados numéricos , Feminino , Humanos , Lactente , Masculino , Saúde Pública/métodos , Saúde Pública/estatística & dados numéricos , Refugiados/psicologia , Refugiados/estatística & dados numéricos , Síria
11.
World J Emerg Surg ; 4: 38, 2009 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-19909508

RESUMO

Munchausen syndrome is a rare psychiatric disorder in which patients inflict on themselves an illness or injury for the primary purpose of assuming the sick role. Because these patients can present with many different complaints and clinical symptoms, diagnosis is often made at a later stage of hospitalisation. In contrast we report a case of a 40-year old woman very easy to diagnose with Munchausen syndrome.This trained nurse presented at our emergency department (ED) complaining of abdominal pain. Interviewed by the medical trainee, she immediately confessed having put a knitting needle into her urethra four days earlier. She was not able to remove it anymore because it was beyond her reach. Abdominal X-ray confirmed the presence of the needle and a median laparotomy was performed to remove it. The diagnosis of Munchausen syndrome seemed immediately obvious in this case.

12.
Crit Care Med ; 34(6): 1661-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16607233

RESUMO

OBJECTIVE: To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical, surgical, or mixed medical/surgical intensive care units. PATIENTS: A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%. INTERVENTIONS: Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n=48) or matching placebo (n=25) for up to 4 wks. MEASUREMENTS AND MAIN RESULTS: Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo. CONCLUSION: Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.


Assuntos
Anemia/tratamento farmacológico , Eritropoetina/farmacocinética , Hematínicos/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Estado Terminal , Método Duplo-Cego , Esquema de Medicação , Epoetina alfa , Contagem de Eritrócitos , Eritropoetina/administração & dosagem , Eritropoetina/sangue , Feminino , Seguimentos , Hematínicos/administração & dosagem , Hemoglobinas/metabolismo , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Estudos Retrospectivos , Resultado do Tratamento
13.
Pediatr Res ; 59(1): 131-6, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16327012

RESUMO

Endothelins (ET) have opposite vascular effects mediated through different receptors: ET(A) receptors mediating vasoconstriction and ET(B) receptors mediating vasoconstriction as well as vasodilation. The role of ET in acute hypoxic pulmonary vasoconstriction (HPV) was studied after dual ET receptor blockade with bosentan and nitric oxide (NO) synthase inhibition with nitro-L-arginine (L-NA). We started from the hypothesis that ET antagonism may inhibit HPV but, if not, would do so after NO synthase inhibition. HPV was evaluated in anesthetized lambs, with an intact pulmonary circulation, by the increase in the mean pulmonary artery pressure (Ppa) minus occluded Ppa (Ppao) gradient in response to hypoxia (inspiratory oxygen fraction of 0.1) at different levels of pulmonary flow (multipoint pressure/flow relationships). ET receptor antagonism decreased pulmonary and systemic vascular tone both in hyperoxia and hypoxia. ET antagonism had no effect on HPV. NO synthase inhibition increased pulmonary vascular tone more in hypoxia than in hyperoxia so that HPV was enhanced. After L-NA, bosentan still decreased pulmonary vascular tone in hypoxia but did not affect the magnitude of HPV. The present results suggest that ET and NO are involved in the regulation of basal pulmonary vascular tone. Furthermore, the vasodilator effect of bosentan persisted in the presence of NO synthase inhibition, suggesting a non NO-dependent vasodilator mechanism. The results from these experiments are in agreement with the idea that ET do not play a major role in HPV in the perinatal lamb, even when it is enhanced by NO synthase inhibition.


Assuntos
Endotelinas/fisiologia , Hiperóxia/fisiopatologia , Hipóxia/fisiopatologia , Óxido Nítrico/fisiologia , Circulação Pulmonar , Animais , Animais Recém-Nascidos , Pressão Sanguínea , Bosentana , Constrição Patológica/fisiopatologia , Dilatação Patológica/fisiopatologia , Antagonistas dos Receptores de Endotelina , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroarginina/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar/efeitos dos fármacos , Carneiro Doméstico , Sulfonamidas/farmacologia , Resistência Vascular/efeitos dos fármacos
14.
Circulation ; 110(15): 2220-5, 2004 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-15466636

RESUMO

BACKGROUND: The phosphodiesterase type-5 (PDE-5) inhibitor sildenafil has been reported to improve pulmonary arterial hypertension (PAH), but the mechanisms that account for this effect are incompletely understood. Severe pulmonary hypertension has been characterized by defects in a signaling pathway involving angiopoietin-1 and the bone morphogenetic receptor-2 (BMPR-2). We investigated the effects of sildenafil on hemodynamics and signaling molecules in a piglet overcirculation-induced model of early PAH. METHODS AND RESULTS: Thirty 3-week-old piglets were randomized to placebo or sildenafil therapy 0.75 mg/kg TID after anastomosis of the left subclavian artery to the pulmonary arterial trunk or after a sham operation. Three months later, the animals underwent a hemodynamic evaluation followed by pulmonary tissue sampling for morphometry, immunohistochemistry or radioimmunoassay, and real-time quantitative-polymerase chain reaction. Chronic systemic-to-pulmonary shunting increased pulmonary mRNA for angiopoietin-1, endothelin-1 (ET-1), angiotensin II, inducible nitric oxide synthase, vascular endothelial growth factor, and PDE-5. Pulmonary messenger RNA for BMPR-1A and BMPR-2 decreased. Pulmonary angiotensin II, ET-1, and vascular endothelial growth factor proteins increased. Pulmonary artery pressure increased from 20+/-2 to 33+/-1 mm Hg, and arteriolar medial thickness increased by 91%. The expressions of angiopoietin-1, ET-1, and angiotensin II were tightly correlated to pulmonary hypertension. Sildenafil prevented the increase in pulmonary artery pressure, limited the increase in medial thickness to 41%, and corrected associated biological perturbations except for the angiopoietin-1/BMPR-2 pathway, PDE-5, and angiotensin II. CONCLUSIONS: Sildenafil partially prevents overcirculation-induced PAH and associated changes in signaling molecules. Angiotensin II, PDE-5, and angiopoietin-1/BMPR-2 signaling may play a dominant role in the early stages of the disease.


Assuntos
Angiopoietina-1/fisiologia , Hipertensão Pulmonar/prevenção & controle , Inibidores de Fosfodiesterase/uso terapêutico , Piperazinas/uso terapêutico , Proteínas Serina-Treonina Quinases/fisiologia , Transdução de Sinais/efeitos dos fármacos , 3',5'-GMP Cíclico Fosfodiesterases , Anastomose Cirúrgica/efeitos adversos , Angiopoietina-1/biossíntese , Angiopoietina-1/genética , Angiotensina II/biossíntese , Angiotensina II/genética , Animais , Arteríolas/ultraestrutura , Receptores de Proteínas Morfogenéticas Ósseas Tipo I , Receptores de Proteínas Morfogenéticas Ósseas Tipo II , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Avaliação Pré-Clínica de Medicamentos , Endotelina-1/biossíntese , Endotelina-1/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperplasia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Modelos Animais , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/biossíntese , Diester Fosfórico Hidrolases/efeitos dos fármacos , Diester Fosfórico Hidrolases/genética , Piperazinas/farmacologia , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Artéria Pulmonar/cirurgia , Purinas , RNA Mensageiro/biossíntese , Distribuição Aleatória , Receptores de Fatores de Crescimento/biossíntese , Receptores de Fatores de Crescimento/genética , Citrato de Sildenafila , Artéria Subclávia/cirurgia , Sulfonas , Sus scrofa , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
15.
Crit Care ; 8(4): R163-71, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15312214

RESUMO

INTRODUCTION: The role played by several vasoactive mediators that are synthesized and released by the pulmonary vascular endothelium in the regulation of hypoxic pulmonary vasoconstriction (HPV) remains unclear. As a potent vasoconstrictor, angiotensin II could be involved. We tested the hypothesis that angiotensin-converting enzyme inhibition by enalaprilat and type 1 angiotensin II receptor blockade by candesartan would inhibit HPV. METHODS: HPV was evaluated in anaesthetized dogs, with an intact pulmonary circulation, by examining the increase in the Ppa-Ppao gradient (mean pulmonary artery pressure minus occluded pulmonary artery pressure) that occurred in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Plasma renin activity and angiotensin II immunoreactivity were measured to determine whether activation or inhibition of the renin-angiotensin system was present. RESULTS: Administration of enalaprilat and candesartan did not affect the Ppa-Ppao gradient at baseline or during hypoxia. Plasma renin activity and angiotensin II immunoreactivity increased during hypoxia, and subsequent measurements were consistent with effective angiotensin-converting enzyme inhibition after administration of enalaprilat, and with angiotensin receptor blockade after administration of candesartan. CONCLUSION: These results suggest that, although the renin-angiotensin system was activated in hypoxia, angiotensin II is not normally involved in mediating acute HPV.


Assuntos
Angiotensina II/antagonistas & inibidores , Endotélio Vascular/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/tratamento farmacológico , Pulmão/irrigação sanguínea , Sistema Renina-Angiotensina/efeitos dos fármacos , Vasoconstritores/antagonistas & inibidores , Angiotensina II/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Benzimidazóis/farmacologia , Compostos de Bifenilo , Cães , Enalaprilato/farmacologia , Endotélio Vascular/fisiopatologia , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Modelos Animais , Tetrazóis/farmacologia , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasoconstritores/metabolismo
16.
Eur J Emerg Med ; 11(3): 172-5, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15167181

RESUMO

The metabolic effects of chronic alcohol abuse can induce a broad spectrum of disorders. We describe the case of an initially unidentified alcoholic, poorly nourished woman who presented with ketoacidosis. She developed severe cardiac failure, which did not respond to classical treatment. The administration of intravenous thiamine resulted in an impressive recovery of cardiac function. Laboratory examinations confirmed the diagnosis of alcoholic ketoacidosis and cardiac beriberi. The clinical entity and treatment of these two uncommon disorders are discussed. If recognized early both diseases (and their combination) are fully reversible.


Assuntos
Alcoolismo/complicações , Serviços Médicos de Emergência/métodos , Insuficiência Cardíaca/etiologia , Cetose/etiologia , Alcoolismo/diagnóstico , Beriberi/diagnóstico , Beriberi/tratamento farmacológico , Caquexia/etiologia , Caquexia/terapia , Diagnóstico Diferencial , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Cetose/diagnóstico , Cetose/terapia , Pessoa de Meia-Idade , Nutrição Parenteral Total/métodos , Choque Séptico/diagnóstico , Tiamina/uso terapêutico , Resultado do Tratamento
17.
Intensive Care Med ; 29(6): 1003-1006, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12734647

RESUMO

OBJECTIVE: To investigate the effects of endogenous endothelins on pulmonary haemodynamics and gas exchange in oleic acid lung injury. DESIGN: Prospective experimental study in dogs. SETTING: Animal research laboratory in a university teaching hospital. SUBJECTS. Seventeen anaesthetised and ventilated mongrel dogs. INTERVENTIONS: Nine pretreated dogs received an infusion of the endothelin A and B receptor antagonist bosentan (10 mg/kg) started before oleic acid. Eight treated dogs received bosentan started 90 min after oleic acid. Cardiac index (CI) was manipulated by inflating an inferior vena caval balloon or by opening a femoral arterio-venous bypass. MEASUREMENTS AND RESULTS: Pulmonary vascular resistance was defined by measuring the gradient between mean pulmonary artery pressure (MPAP) and occluded PAP (PAOP) at five levels of CI. Intrapulmonary shunt was measured using the inert gas SF(6). Pretreatment with bosentan prevented the oleic acid-induced shift of (MPAP-PAOP)/CI plots to higher pressures, but did not affect the increase in intrapulmonary shunt. Treatment of established oleic acid lung injury with bosentan had no effect. CONCLUSIONS: Pretreatment, but not treatment, with bosentan, in the dose used, blunted the oleic acid-induced increase in pulmonary vascular resistance, suggesting that endothelins contribute to the increase in pulmonary vascular tone in the early stages of oleic acid lung injury.


Assuntos
Anti-Hipertensivos/uso terapêutico , Modelos Animais de Doenças , Antagonistas dos Receptores de Endotelina , Síndrome do Desconforto Respiratório/tratamento farmacológico , Sulfonamidas/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Bosentana , Cães , Avaliação Pré-Clínica de Medicamentos , Infusões Intravenosas , Ácido Oleico , Estudos Prospectivos , Circulação Pulmonar/efeitos dos fármacos , Troca Gasosa Pulmonar/efeitos dos fármacos , Pressão Propulsora Pulmonar/efeitos dos fármacos , Receptor de Endotelina A , Receptor de Endotelina B , Receptores de Endotelina/fisiologia , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/fisiopatologia , Sulfonamidas/farmacologia , Resistência Vascular/efeitos dos fármacos
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