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Acute liver failure is a rare but potentially devastating disease. Throughout the last few decades, acute liver failure outcomes have been improving in the context of the optimized overall management. This positive trend has been associated with the earlier recognition of this condition, the improvement of the intensive care unit management, and the developments in emergent liver transplantation. Accordingly, we aimed to review the current diagnostic and therapeutic approach to this syndrome, especially in the intensive care unit setting. info:eu-repo/semantics/publishedVersion

The liver transplant program in our center started in 1992, and post-liver transplant patients are still admitted to the intensive care unit. For the intensive care physician, a learning curve started then, skills were acquired, and a specific practice was established. Throughout this time, several concepts changed, improving the care of these patients. The practical approach varies between liver transplant centers, according to local specificities. Hence, we wanted to present our routine practice to stimulate the debate between dedicated teams, which can allow the introduction of new ideas and potentially improve each local standard of care.O programa de transplante de fígado teve início em nosso centro em 1992, e pacientes em pós-operatório de transplante hepático ainda são admitidos à unidade de terapia intensiva. Uma curva de aprendizado do médico intensivista teve então início, com aquisição de habilidades e estabelecimento de uma prática específica. Contudo, muitos dos conceitos se modificaram com o tempo, o que conduziu a uma melhora nos cuidados proporcionados a esses pacientes. A abordagem prática varia entre diferentes centros de transplante de fígado, segundo especificidades locais. Assim, ensejamos apresentar nossa prática para estimular o debate entre diferentes equipes dedicadas, o que tem potencial de permitir a introdução de novas ideias e, possivelmente, melhorar o padrão de cuidados em cada instituição.

Objective To access the incidence of infectious problems after liver transplantation (LT). Design A retrospective, single-center study. Materials and Methods Patients undergoing LT from January 2008 to December 2011 were considered. Exclusion criterion was death occurring in the first 48 hours after LT. We determined the site of infection and the bacterial isolates and collected and compared recipient's variables, graft variables, surgical data, post-LT clinical data. Results Of the 492 patients who underwent LT and the 463 considered for this study, 190 (Group 1, 41%) developed at least 1 infection, with 298 infections detected. Of these, 189 microorganisms were isolated, 81 (51%) gram-positive bacteria (most frequently Staphylococcus spp). Biliary infections were more frequent (mean time of 160.4 ± 167.7 days after LT); from 3 months after LT, gram-negative bacteria were observed (57%). Patients with infections after LT presented lower aminotransferase levels, but higher requirements in blood transfusions, intraoperative vasopressors, hemodialysis, and hospital stay. Operative and cold ischemia times were similar. Conclusion We found a 41% incidence of all infections in a 2-year follow-up after LT. Gram-positive bacteria were more frequent isolated; however, negative bacteria were commonly isolated later. Clinical data after LT were more relevant for the development of infections. Donors' variables should be considered in future analyses.

Background In a liver transplant (LT) center, treatments with Prometheus were evaluated. The main outcome considered was 1 and 6 months survival. Methods During the study period, 74 patients underwent treatment with Prometheus; 64 were enrolled, with a mean age of 51 ± 13 years; 47 men underwent 212 treatments (mean, 3.02 per patient). The parameters evaluated were age, sex, laboratorial (liver enzymes, ammonia) and clinical (model for end-stage liver disease and Child-Turcotte-Pugh score) data. Results Death was verified in 23 patients (35.9%) during the hospitalization period, 20 patients (31.3%) were submitted to liver transplantation, and 21 were discharged. LT was performed in 4 patients with acute liver failure (ALF, 23.7%), in 7 patients with acute on chronic liver failure (AoCLF, 43.7%), and in 6 patients with liver disease after LT (30%). Seven patients who underwent LT died (35%). In the multivariate analysis, older age ( P = .015), higher international normalized ratio (INR) ( P = .019), and acute liver failure ( P = .039) were independently associated with an adverse 1-month clinical outcome. On the other hand, older age ( P = .011) and acute kidney injury ( P = .031) at presentation were both related to worse 6-month outcome. For patients with ALF and AoCLF we did not observe the same differences. Conclusions In this cohort, older age was the most important parameter defining 1- and 6-month survival, although higher INR and presence of ALF were important for 1-month survival and AKI for 6-month survival. No difference was observed between patients who underwent LT or did not have LT.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of a patient with cirrhosis, frequently associated with multi-organ failure and a high short-term mortality rate. We present a retrospective study that aims to characterize the presentation, evolution, and outcome of patients diagnosed with ACLF at our center over the last 3 years, with a comparative analysis between the group of patients that had ACLF precipitated by infectious insults of bacterial origin and the group of those with ACLF triggered by a nonbacterial infectious insult; the incidence of acute kidney injury and its impact on the prognosis of ACLF was also analyzed. Twenty-nine patients were enrolled, the majority of them being male (89.6%), and the mean age was 53 years. Fourteen patients (48.3%) developed ACLF due to a bacterial infectious event, and 9 of them died (64.2%, overall mortality rate 31%); however, no statistical significance was found (p < 0.7). Of the remaining 15 patients (51.7%) with noninfectious triggers, 11 died (73.3%, overall mortality rate 37.9%); again there was no statistical significance (p < 0.7). Twenty-four patients (83%) developed acute kidney injury (overall mortality rate 65.5%; p < 0.022) at the 28-day and 90-day follow-up. Twelve patients had acute kidney injury requiring renal replacement therapy (41.37%; overall mortality rate 37.9%; p < 0.043). Hepatic transplant was performed in 3 patients, with a 100% survival at the 28-day and 90-day follow-up (p < 0.023). Higher grades of ACLF were associated with increased mortality (p < 0.02; overall mortality 69%). Conclusions: ACLF is a heterogeneous syndrome with a variety of precipitant factors and different grades of extrahepatic involvement. Most cases will have some degree of renal dysfunction, with an increased risk of mortality. Hepatic transplant is an efficient form of therapy for this syndrome. A Doença Hepática Crónica Agudizada/Falência é um síndrome caracterizado por uma deterioração aguda de um doente com cirrose, frequentemente associada com falência multiorgânica e elevada mortalidade a curto prazo. Apresentamos estudo retrospetivo que teve como objetivo caracterizar a apresentação, evolução e prognóstico de doentes diagnosticados com Doença Hepática Crónica Agudizada/Falência no nosso Centro nos últimos 3 anos, comparando o grupo de doentes que tiveram Doença Hepática Crónica provocada por infeções bacterianas e os doentes com Doença Hepática Crónica Agudizada/Falência desencadeada por precipitantes que não a infeção bacteriana; foi também analisada a incidência de lesão renal aguda e o seu impacto no prognóstico na Doença Hepática Crónica Agudizada/Falência. Vinte e nove doente foram incluídos no estudo, a maioria do género masculino (89.6%), idade media de 53 anos. Catorze doentes (48.3%) desenvolveram Doença Hepática Crónica Agudizada devido a infeção bacteriana, 9 dos quais faleceram (64.2%, mortalidade global 31%), contudo, sem significado estatístico (p < 0.7); dos restantes 15 (51.7%) sem infeção bacteriana, 11 faleceram (73.3%, mortalidade global 37.9%), também sem significado estatístico (p < 0.7%). Vinte e quatro doentes (83%) desenvolveram lesão renal, mortalidade global de 65.5% (p < 0.022) aos 28 e 90 dias de seguimento. Doze doentes desenvolveram lesão renal aguda com necessidade de terapêutica de substituição da função renal (41.37%), mortalidade global de 37.9% ( p < 0.043). O transplante hepático foi realizado em 3 doentes, com uma sobrevida de 100% aos 28 e 90 dias de seguimento (p < 0.023); Graus elevados de Doença Hepática Crónica Agudizada estão associadas a mortalidade mais elevada (p < 0.02); mortalidade global de 69%. Conclusions: A Doença Hepática Crónica Agudizada é um síndrome heterogéneo, com uma variedade de fatores precipitantes e diferentes graus de envolvimento extra-hepático; a maioria das situações estará associada a disfunção renal, com aumento do risco de mortalidade; O transplante hepático será uma eficaz de tratamento deste síndrome.

Background: Ischaemia-reperfusion injury (IRI), a major complication occurring during organ transplantation, involves an initial ischemia insult, due to loss of blood supply, followed by an inflammation-mediated reperfusion injury. A variety of molecular targets and pathways involved in liver IRI have been identified. Gene silencing through RNA interference (RNAi) by means of small interference RNA (siRNA) targeting mediators of IRI is a promising therapeutic approach. Objective: This study aims at reviewing the use of siRNAs as therapeutic agents to prevent IRI during liver transplantation. Method: We review the crucial choice of siRNA targets and the advantages and problems of the use of siRNAs. Results: We propose possible targets for siRNA therapy during liver IRI. Moreover, we discuss how drug delivery systems, namely liposomes, may improve siRNA therapy by increasing siRNA stability in vivo and avoiding siRNA off-target effects. Conclusion: siRNA therapeutic potential to preclude liver IRI can be improved by a better knowledge of what molecules to target and by using more efficient delivery strategies.

In this prospective study, we comparatively evaluated the accuracy of several biomarkers of acute kidney injury (AKI) on predicting its occurrence after liver transplantation (LT). The parameters evaluated were urinary tubular enzymes (γ-glutamyl transpeptidase [γGT], alkaline phosphatase, and urinary lactate dehydrogenase) and urinary neutrophil gelatinase–associated lipocalin. These parameters were evaluated both as isolated variables and divided by urinary creatinine. Samples were collected by the end of surgery (determination 1) and at 12 to 24 hours after surgery (determination 2). The study endpoint was the development of AKI. The study was performed over a 1-year period, and 61 of 77 patients were enrolled (main exclusion criteria were perioperative death, previous known renal failure, and insufficient data for analysis). Of these 61 patients, AKI was observed in 19 (group 1). The main relevant parameter to predict AKI was the absolute value of urinary γGT at determination 1 (area under the curve, 0.74; specificity, 72.5%; sensitivity, 70.3%; cutoff, 36 U/mL). Urinary neutrophil gelatinase–associated lipocalin was not as accurate; the best predicted value for this parameter was absolute value at D1 with an area under the curve of 0.5 (specificity, 84.2%; sensitivity, 35.7%; cutoff value, 44.6 ng/mL). We concluded that the absolute value of urinary γGT evaluated at the end of LT was the most accurate parameter to predict AKI in our cohort. Urinary enzyme levels must be taken into account in future analysis of this issue.

An innovative technique for pancreas transplantation is described. The main aspect consists of the horizontal positioning of the pancreas, which allows a better venous outflow, thus preventing thrombosis and graft loss. The program of pancreas transplantation in this national reference center for pancreatic and liver surgery was started in 2007; the initial results were considered poor, resulting in the loss of half of the grafts due to venous thrombosis. After analyzing the possible causes, this technique was proposed and successfully implemented, reducing the postoperative complications, particularly the problem of venous thrombosis. A detailed description of the new surgical technique is provided. The main clinical and demographic characteristics of the 56 patients who underwent the surgery are analyzed. The incidence of venous thrombosis was 5.3% (3 patients) and graft loss was 3.5% (2 patients). Due to the good results, this technique became the standard surgery for transplantation of the pancreas in our center. The technique proved to be safe and successful. Due to the unique pancreas graft implantation, we called it "transverse pancreas surgery." info:eu-repo/semantics/publishedVersion

The goal of hemodynamic monitoring and management during major surgery is to guarantee adequate organ perfusion, a major prerequisite for adequate tissue oxygenation and thus, end-organ function. Further, hemodynamic monitoring should serve to prevent, detect, and to effectively guide treatment of potentially life-threatening hemodynamic events, such as severe hypovolemia due to hemorrhage, or cardiac failure. The ideal monitoring device does not exist, but some conditions must be met: it should be easy and operator-independently to use; it should provide adequate, reproducible information in real time. In this review we discuss in particular the role of intraoperative use of transesophageal echocardiography (TOE). Although TOE has gained special relevance in cardiac surgery, its role in major non cardiac surgery is still to be determined. We particularly focus on its ability to provide measurements of cardiac output (CO), and its role to guide fluid therapy. Within the last decade, concepts oriented on optimizing stroke volume and cardiac output mainly by fluid administration and guided by continuous monitoring of cardiac output or so called functional parameters of cardiac preload gained particular attention. Although they are potentially linked to an increased amount of fluid infusion, recent data give evidence that such pre-emptive concepts of hemodynamic optimization result in a decrease in morbidity and mortality. As TOE allows a real time direct visualization of cardiac structures, other potentially important advantages of its use also outside the cardiac surgery operation room can be postulated, namely the ability to evaluate the anatomical and functional integrity of the left and the right heart chambers. Finally, a practical approach to TOE monitoring is presented, based on a local experience.

This study sought to evaluate the potential impact of domino liver transplantation (DLT) on initial graft function and early postoperative outcome in patients with cirrhosis in a Portuguese liver transplantation center. A retrospective comparative analysis was performed between 77 domino recipients (from familial amyloidotic polyneuropathy donors) and 91 deceased donor recipients, all submitted to primary elective whole liver transplantation, using the piggyback technique, in a 42-month period. Outcome parameters included graft dysfunction (defined as either primary nonfunction or initial poor function, according to the Ploeg-Maring criteria) and Clavien II-IV complications in the first postoperative week. Domino and deceased donor recipients had similar preoperative severity indices (Child-Pugh classification and Model for End-Stage Liver Disease score) and immediate postoperative severity scores (APACHE II [Acute Physiology and Chronic Health Evaluation II] and SAPS II [Simplified Acute Physiology Score II]). In DLT, donors were younger, cold ischemia time was shorter, and intraoperative transfusion requirements of packed red blood cells and fresh-frozen plasma were significantly lower. Graft dysfunction incidence was 3.4-fold lower in DLT: 5.2% (only 4 cases of initial poor function) versus 18.0% (1 primary nonfunction and 15 cases of initial poor function), P = 0.010. Postoperative bleeding was the most frequent early Clavien II-IV complication (n = 29, 17.3%), with an incidence 2.2-fold lower in domino recipients. A statistically significant difference was not found in the other analyzed Clavien II-IV complications, intensive care unit stay, mechanical ventilation time, intensive care unit mortality, and 1-year survival rate. In conclusion, in this study the younger donors and shorter ischemic time associated with DLT may provide a protective role in regards to graft dysfunction and perioperative bleeding, which are 2 important determinants of early morbidity after liver transplantation.

Echocardiography is a non-invasive tool, aimed towards the anatomical and functional characterization of the heart. In Intensive Care it is considered nowadays as a necessary tool for patient evaluation. However, the information obtained using echocardiography is not the same as provided by other means, namely the invasive ones. In recent years there has been a significant evolution in the general concepts of haemodynamic support for the critically ill patient. In this new environment, echocardiography has gained particular relevance. In this text the new positioning of echocardiography in the light of the new concepts for hemodynamic support is described, as well as, the need for a specific formative program directed towards Intensive Care physicians. A new generation of biomarkers can also add relevant information and start a new era in haemodynamic support. They may help to further characterize the disease process, identifying patients at risk, as well as, characterize specific organ failure as well as monitoring therapy.

Tubular enzymes (TE) are early markers of acute kidney injury (AKI), but their value for liver transplant (LT) recipients is unknown. We sought to evaluate the usefulness of TE to predict AKI after LT. We enrolled Thirty-nine adult patients without AKI who had been admitted to the Intensive Care Unit (ICU). AKI was diagnosed according to the Acute Kidney Injury Network criteria. Of these patients, 23 had received orthotopic LT and 16 controls had been admitted for other conditions. Urinary lactate dehydrogenase (LDH), alkaline phosphatase (AF) and γ-glutamyl transpeptidase (γ-GT) measured on days 1 and 3 of the ICU stay were normalized to urinary creatinine concentrations. AKI was diagnosed in 14 patients: 8 in the LT group and 6 in the control group. In the LT group, on the first day of the patients' stay in the ICU, urinary LDH (P = .032), AF (P = .022), and γ-GT (P = .002) were significantly higher among those who developed AKI; these elevations preceded those of serum creatinine. In forward receiver-operating characteristic (ROC) plot analysis, the areas under the ROC curves were 0.8, 0.86, and 0.92 for LDH, AF, and γ-GT, respectively. We concluded that TE determined early after LT are a helpful predictors of AKI.

The authors analyzed 704 transthoracic echocardiographic (TTE) examinations, performed routinely to all admitted patients to a general 16-bed Intensive Care Unit (ICU) during an 18-month period. Data acquisition and prevalence of abnormalities of cardiac structures and function were assessed, as well as the new, previously unknown severe diagnoses. A TTE was performed within the first 24 h of admission on 704 consecutive patients, with a mean age of 61.5 ± 17.5 years, ICU stay of 10.6 ± 17.1 days, APACHE II 22.6 ± 8.9, and SAPS II 52.7 ± 20.4. In four patients, TTE could not be performed. Left ventricular (LV) dimensions were quantified in 689 (97.8%) patients, and LV function in 670 (95.2%) patients. Cardiac output (CO) was determined in 610 (86.7%), and mitral E/A in 399 (85.9% of patients in sinus rhythm). Echocardiographic abnormalities were detected in 234 (33%) patients, the most common being left atrial (LA) enlargement (n = 163), and LV dysfunction (n = 132). Patients with these alterations were older (66 ± 16.5 vs 58.1 ± 17.4, p < 0.001), presented a higher APACHE II score (24.4 ± 8.7 vs 21.1 ± 8.9, p < 0.001), and had a higher mortality rate (40.1% vs 25.4%, p < 0.001). Severe, previously unknown echocardiographic diagnoses were detected in 53 (7.5%) patients; the most frequent condition was severe LV dysfunction. Through a multivariate logistic regression analysis, it was determined that mortality was affected by tricuspid regurgitation (p = 0.016, CI 1.007–1.016) and ICU stay (p < 0.001, CI 1–1.019). We conclude that TTE can detect most cardiac structures in a general ICU. One-third of the patients studied presented cardiac structural or functional alterations and 7.5% severe previously unknown diagnoses.

Resumo: Nos doentes com infecção pelo vírus da imunodeficiência humana (VIH) o citomegalovírus torna-se um agente de doença importante quando existe imunossupressão avançada. O seu papel como agente de doença pulmonar neste contexto tem sido amplamente debatido. Nos doentes com pneumocistose, a presença do citomegalovírus no pulmão não parece conferir pior prognóstico, excepto nos que recebem terapêutica adjuvante com corticóides.Os autores apresentam dois casos de doentes com infecção VIH e imunossupressão avançada, admitidos na unidade de cuidados intensivos por insuficiência respiratória. Em ambos houve isolamento de Pneumocystis jirovecii no lavado broncoalveolar. Apesar da terapêutica instituída ambos vieram a falecer. A biópsia pulmonar post mortem mostrou, nos dois casos, a presença de Pneumocystis e inclusões por citomegalovírus. Perante este achado tecem-se algumas considerações sobre o papel do citomegalovírus como agente de pneumonia na SIDA e sobre o seu significado como co-infectante na pneumocistose, sobretudo nos casos de falência terapêutica.Rev Port Pneumol 2008; XIV (1): 151-157 Abstract: Cytomegalovirus is capable of causing disease in immunocompromised patients. In people infected by the Human Immunodeficiency Virus (HIV) it becomes an important agent when there is advanced immunosupression. Its role as a pulmonary pathogen in these patients has been questioned. In the case of pneumocystosis the presence of Cytomegalovirus doesnât seem to worsen prognosis, except in cases where corticosteroids are used.Authors present two cases of patients with HIV infection and advanced immunosupression who were admitted in the intensive care unit for respiratory failure. In both Pneumocystis jirovecii was isolated from bronco-alveolar lavage. Despite of therapy both patients died from refractory hypoxemia. Pulmonary biopsies performed post mortem revealed presence of Pneumocystis and Cytomegalovirus inclusion bodies. Considering this finding the role of Cytomegalovirus as a cause of pneumonia in AIDS is discussed, highlighting its impact on the outcome of patients with pneumocystosis, especially in cases of therapeutic failure.Rev Port Pneumol 2008; XIV (1): 151-157 Palavras chave: Citomegalovírus, pneumonia, VIH, Key words: Cytomegalovirus, pneumonia, HIV

Pulmonary capillary wedge pressure (Pw) is an important hemodynamic parameter frequently used in Intensive Care. Much effort was taken by investigators to noninvasively obtain this parameter particularly using echocardiography. The authors reviewed the published works in this field. There are a great number of correlations between echocardiographic variables and Pw, including equations for its precise assessment. Changes in echocardiographic parameters due to modifications in volume status and more recently tissue Doppler evaluation are also related fields. Despite the quality and quantity of investigation, no single method was established or accepted for non-invasive assessment of Pw using echocardiography. The major problems are related to the study of different populations regarding its basic clinical condition and to the complexity of equations described. Non-invasive assessment of Pw in clinical setting using echocardiography is still a hard task for this technique. Probably, the use of echocardiography as a non-invasive tool for hemodynamic assessment should use other methodologies, and not rely on Pw determination.

Resumo: Objectivos: Determinar a possibilidade de avaliação não invasiva da pressão venosa central (PVC) através da análise da veia cava inferior (VCI), obtida por ecocardiografia transtorácica (ETT).Desenho: Estudo prospectivo com 3 anos de duração.Local: Unidade de Cuidados Intensivos Polivalente (UCIP) de 16 camas.Métodos: Estudados doentes admitidos numa UCIP nos quais se avaliou a PVC em simultâneo com exame ETT que, para além da visualização da VCI, consistiu na obtenção da dimensão das cavidades cardíacas e função sistólica do ventrículo esquerdo. Para a correlação foram utilizados testes estatísticos paramétricos e não paramétricos.Resultados: Admitidos 560 doentes com registo simultâneo de PVC e ETT e incluídos 477 doentes em que foi possível visualizar a VCI, com idade média de 62,6±±17,3 anos, média de internamento de 11,9±18,7 dias, um índice APACHE II médio de 23,9±8,9 e SAPS II médio de 55,7±20,4. Por análise de regressão linear verificou-se uma relação entre a PVC e a dimensão máxima da VCI (p=0,013), o índice da VCI (p=0,001) e a presença de ventilação mecânica (p=0,002). A correlação linear entre a PVC e a dimensão máxima da VCI e respectivo índice foi de 0,34 e 0,44. Por teste de qui-quadrado, verificou-se uma relação estatisticamente significativa entre os seguintes intervalos de valores: índice da VCI >25% e PVC7 mmHg e a dimensão máxima da VCI >10 mm; nos doentes admitidos por exacerbação de doença pulmonar crónica verificou-se uma correlação fraca entre a PVC >7 mmHg e o índice da VCI25% and a CVP 7 mmHg; an IVC maximum dimension10 mmHg and CVP>7 mmHg. Patients with right ventricle enlargement presented a lack of agreement between IVC maximum dimension and CVP7 mmHg was also observed.Conclusions: IVC analysis is a possible way to noninvasively estimate CVP in a medical/surgical ICU. However, patients with right ventricular enlargement and admitted with chronic respiratory failure present a lack of agreement between IVC parameters and low values of CVP. IVC dimension is a marker of chronic disease and IVC index correlated better with CVP.Rev Port Pneumol 2006; XII (6): 637-658 Palavras-chave: Pressão venosa central, ecocardiografia, cuidados intensivos, doença pulmonar crónica, Key-words: Echocardiography, intensive care, central venous pressure, inferior vena cava, chronic respiratory failure

Objective: To study the influence of cardiac status on the length of mechanical ventilation, outcome and disease severity in patients admitted to an Intensive Care Unit (ICU) with exacerbation of chronic respiratory failure. Design and setting: A 30-month prospective study in a 14 bed ICU Patients and methods: Fifty nine patients were enrolled, with a mean age 74.7 +/- 9.7 years, mean length of ventilator support 10.8 +/- 12.6 days, and mean APACHE II score 23 +/- 8.3. Within the first 24 hours of admittance, cardiac chamber dimensions, inferior vena cava (IVC), and mitral transvalvular Doppler were evaluated using transthoracic echocardiography; the cardiac rhythm was recorded (presence of sinus rhythm or atrial fibrillation). Blood gases were evaluated at discharge. Results: Greater length of ventilation was observed in patients presenting atrial fibrillation (p = 0.027), particularly when a dilated IVC was also present (>20 mm, p = 0.004). A high level of serum bicarbonate (>35 mEq/l), was also related with longer ventilation (p = 0. 04). Twelve patients died. Mortality was related to the presence of a dilated right ventricle (p = 0.03) and a ratio between right and left ventricle > 0. 6 (p = 0.04). Conclusion: Patients submitted to mechanical ventilation due to exacerbation of chronic respiratory failure which present atrial fibrillation require a longer ventilation period, particularly if a dilated IVC is also present. Patients with dilated right cardiac chambers are at an increased risk of a fatal outcome. Resumo: Objectivo: estudar determinantes cardiovasculares condicionantes do tempo de ventilação, mortalidade e gravidade de doença em doentes admitidos numa unidade de cuidados intensivos para ventilação mecânica por exacerbação de insuficiência respiratória crónica. Desenho e local: Estudo prospectivo, com duração de 30 meses numa unidade de cuidados intensivos médico-cirúrgica com 14 camas. Material e métodos: Estudados 59 doentes com idade média de 74,7 +/- 9,7 anos, tempo médio de ventilação de 10,8 +/- 12,6 dias, APACHE II médio de 23 +/- 8,3. Avaliaram-se parâmetros ecocardiográficos (dimensões das cavidades, débito cardíaco, estudo Doppler do fluxo transvalvular mitral, estudo da veia cava inferior) e electrocardiográficos (presença de ritmo sinusal ou fibrilhação auricular) nas primeiras 24 horas de internamento na Unidade e parâmetros gasimétricos à saída. Resultados: Um tempo de ventilação mais prolongado associou-se à presença de fibrilhação auricular (p = 0,027), à presença conjunta de fibrilhação auricular e uma veia cava inferior dilatada (> 20 mm p = 0,004) e com níveis séricos de bicarbonato > 35mEq/l na gasimetria obtida à saída (p = 0,04). Verificaram-se 12 óbitos. A mortalidade associou-se à presença de dilatação do ventrículo direito (p = 0,03) e a uma relação entre o ventrículo direito e o esquerdo > 0,6 (p = 0,04). Conclusão: Nos doentes submetidos a ventilação mecânica por exacerbação de insuficiência respiratória crónica, a presença de fibrilhação auricular indica a possibilidade de um período de ventilação mais prolongado, em especial se houver concomitantemente uma veia cava inferior com diâmetro > 20mm. Nestes doentes, a presença de dilatação das cavidades direitas pode indicar uma probabilidade mais elevada de mortalidade. Key-words: Mechanical ventilation, chronic respiratory failure, echocardiography, Palavras-chave: Insuficiência respiratória crónica, ventilação mecânica, ecocardiografia

This study evaluated the relationship between intraoperative hemodynamic instability (IOHI) and the development of calcineurin inhibitor (CNI) toxicity in the early postoperative period after liver transplantation (LT). Eighty-two patients were enrolled during a 1-year period and a 3-month follow-up. IOHI, requiring continuous infusion of vasopressors, was observed in 31 patients (38%, group 1; control group 2, n = 51). Acute kidney injury (AKI) developed in 28 patients (52% in group 1 vs 24% in group 2, P = .02), and CNI-related neurotoxicity (CNI-NT) in 26 (48% in group 1 vs 22% in group 2, P = .03). Group 1 patients received mainly deceased donor grafts (87% vs 57% in group 2, P < .001). An independent association between IOHI and CNI-NT (P = .029) and AKI (P = .016) was observed. The receiver-operator characteristic curve revealed an area under the curve of 0.63 for IHI (sensitivity 56%; specificity 75%) and 0.65 for AKI (sensitivity 56%; specificity 70.2%). In conclusion, patients undergoing LT with IOHI may be more prone to developing CNI-NT and AKI in the early postoperative period.

This study aimed to compare the histologic and molecular gene expression at several surgical times (beginning of harvesting, T0; end of cold ischemia period, T1; and after reperfusion, T2) to characterize the ischemia-reperfusion injury (IRI) in deceased-donor liver grafts harvested from patients with familial amyloidotic polyneuropathy (FAP). For this purpose, 54 patients undergoing liver transplantation were studied and divided into 3 groups: deceased donor to cirrhotic recipient (group 1; n = 27), deceased donor to FAP recipient (group 2; n = 15), and FAP donor to cirrhotic recipient (group 3; n = 12). The main comparison was performed between a histologic score (Suzuki score, adding steatosis and neutrophil infiltration), and molecular gene expression of the following genes: interleukin (IL) 1β, IL-6, E-selectin, Fas-ligand, granzyme B, heme oxygenase 1 (HO1), and nitric oxide synthetase (iNOS2A). We observed less neutrophil infiltration levels in group 3 in sample T0 (P = .0082), which was associated with gene expression of HO1 in the biopsies at T2 (P = .022). In group 3, the molecular expression of genes related to attenuated proinflammatory reaction during IRI, iNOS2A at T0 and HO1 at T2, was detected. We conclude that FAP liver grafts express differently the genes associated with an attenuated proinflammatory reaction, presenting less neutrophil infiltration at harvesting. These findings add more knowledge about the better short-term outcomes in patients receiving this type of liver graft.

In this study the authors evaluated the efficacy of prophylaxis with liposomal amphotericin B (L-AmB) in the incidence of fungal infections (FI) during the first 3 months after liver transplant (LT). The study was retrospective and accessed a 4-year period from 2008 to 2011. All patients who died in the first 48 hours after LT were excluded. Patients were divided by the risk groups for FI: Group 1, high-risk (at least 1 of the following conditions: urgent LT; serum creatinine >2 mg/dL; early acute kidney injury [AKI] after LT; retransplantation; surgical exploration early post-LT; transfused cellular blood components [>40 U]); and Group 2, low-risk patients. Group 1 patients were further separated into those who received antifungal prophylaxis with L-AmB and those who did not. Prophylaxis with L-AmB consisted of intravenous administration of L-AmB, 100 mg daily for 14 days. Four hundred ninety-two patients underwent LT; 31 died in the first 48 hours after LT. From the remaining 461 patients, 104 presented with high-risk factors for FI (Group 1); of these, 66 patients received antifungal prophylaxis and 38 did not. In this group 8 FI were observed, 5 in patients without antifungal prophylaxis (P = .011). Three more FI were identified in Group 2. By logistic regression analysis, the categorical variable high-risk group was independently related to the occurrence of invasive FI (P = .006). We conclude that prophylaxis with L-AmB after LT was effective in reducing the incidence of FI. No influence on mortality was detected.

In Intensive Care Medicine (ICM) the presence of multiple high tech devices is common in order to perform multiple medical and non-medical procedures. The authors intend to perform a critical appraisal on the basic and practical/clinical approach to monitoring devices, analyzing the evidence support regarding clinical effects, end-points, and patient safety. All data that provides a diagnosis or a characterization of the patient’s status will be considered diagnostic information whereas, variables that could be achieved by medical interventions will be considered therapeutic end-points. In any healthcare setting a careful approach to the patient is needed, namely in ICM one must consider the patient’s clinical condition and choose adequate diagnostic tools and devices. Not all variables and devices currently on the market are suitable for each patient, nor proved useful in the setting under study. Also, all patients are different and must be approached differently according to established clinical end-points, translating into more holistic caregiving. ICM requires a personalized approach towards the patient, consequently, submitting diagnostic tools and monitoring devices to greater scrutiny in order to obtain greater patient benefit.

A pilot study aimed to introduce intraoperative monitoring of liver surgery using transoesophageal echocardiography (TEE) is described. A set of TEE measurements was established as a protocol, consisting of left atrial (LA) dimension at the aortic valve plane; mitral velocity flow integral, calculation of stroke volume and cardiac output (CO); mitral annular plane systolic excursion; finally, right atrial area. A total of 165 measurements (on 21 patients) were performed, 31 occurring during hypotension. The conclusions reached were during acute blood loss LA dimension changed earlier than CVP, and, in one patient, a dynamic left ventricular (LV) obstruction was observed; in 3 patients a transient LV systolic dysfunction was documented. The comparison between 39 CO paired measurements obtained by TEE and PiCCO2 revealed a statistically significant correlation (P<0.001,r=0.83). In this pilot study TEE successfully answered the questions raised by the anesthesiologists. Larger cohort studies are needed to address this issue.

Resumo: Objectivos: A insuficiência respiratória parcial aguda (IRPA) grave é uma situação comum na prática dos cuidados intensivos, mas os estudos existentes são insuficientes. Com este trabalho pretendeu-se estudar a prevalência e caracterizar clinicamente a população de doentes internados numa UCI que apresentam insuficiência respiratória parcial aguda grave.Material e métodos: Numa unidade de cuidados intensivos médico-cirúrgica avaliaram-se retrospectiva-mente os doentes internados durante o ano de 2004.Resultados: 37,6% dos doentes apresentaram IRPA grave. A análise estatística demonstrou que estes doentes diferiam dos doentes sem IRPA nos tempos de internamento e ventilação, índices de gravidade e mortalidade.Conclusão: A IRPA é uma situação com elevada prevalência e relevância em cuidados intensivos, mas as carac-terísticas destes doentes estão mal definidas, em parte devido à ausência de critérios claros na sua definição. Para melhor compreender este fenómeno são necessá-rios mais estudos, prospectivos e multicêntricos.Rev Port Pneumol 2008; XIV (3): 339-352 Abstract: Objective: The authors analysed patients with severe partial respiratory failure (SPRF) admitted to a general Intensive Care Unit (ICU). The prevalence and clinical characteristics of these patients were evaluated.This work aims to study the rate of and to clinically characterise the patient population admitted to an Intensive Care Unit with acute severe partial respiratory failure.Material and methods: In 16-bed ICU of a central Hospital in Lisbon, patients admitted in the year 2004 were analysed. Patients with SPRF were recruited form patients with an ICU stay>24 hours. They were selected according to PaO2 and FiO2 and clinically characterized.Results: During the study period 472 patients were admitted, and 378 presented an ICU stay>24 hours and were enrolled. From those, 142 (37.6%) met criteria for SPRF. Of these, 45 (31.7%) a pulmonary aetiology of SPRF was identified. Patients with SRPF were older, had longer ICU stay, and presented higher severity indexes and mortality.The prevalence of adult respiratory distress syndrome was possible to evaluate in the deceased patients with SPRF (n=52). In these we could find 12 (23%) patients that met criteria for that entity. By multivariate analysis the mortality of patients with SRPF correlated with older age and the presence of circulatory failure (p

Objectives: To determine the possibility of non-invasive estimation of central venous pressure (CVP) through inferior vena cava (IVC) analysis, using transthoracic echocardiography (TTE). Design: A prospective 3-year study. Setting: A 16-bed medical/surgical Intensive Care Unit (ICU). Methods: Patients admitted to the ICU were enrolled. CVP measurement and TTE (determining cardiac chambers dimension and left ventricular shortening fraction) with IVC analysis (maximum dimension and IVC index) were performed simultaneously. Parametric and non-parametric statistical analysis was performed to establish correlations between variables. Results: 560 patients were admitted to the study, including 477 in whom IVC was analysed, aging 62.2 ± 17.3 years, a mean ICU stay 11.9 ± 18.7 days, a APACHE II score 23.9 ± 8.9 and a SAPS II score 55.7 ± 20.4. Through linear regression analysis CVP was influenced by IVC index (p=0.001), IVC maximum dimension (p=0.013) and presence of mechanical ventilation (p=0.002). A statistically significant correlation was found between the following parameters: an IVC index< 25% and a CVP >13 mmHg; an IVC index and a CVP 26%-50%; an IVC index >51% and CVP< 7 mmHg; an IVC maximum dimension > 20 mm and a CVP >13 mmHg; an IVC maximum dimension 7 mmHg was observed, and in patients with chronic respiratory failure (who presented a high prevalence of right ventricular enlargement) a lack of agreement between IVC index >50% and CVP< 7 mmHg was also observed. Conclusions: IVC analysis is a possible way to noninvasively estimate CVP in a medical/surgical ICU. However, patients with right ventricular enlargement and admitted with chronic respiratory failure present a lack of agreement between IVC parameters and low values of CVP. IVC dimension is a marker of chronic disease and IVC index correlated better with CVP. Resumo: Objectivos: Determinar a possibilidade de avaliação não invasiva da pressão venosa central (PVC) através da análise da veia cava inferior (VCI), obtida por ecocardiografia transtorácica (ETT). Desenho: Estudo prospectivo com 3 anos de duração. Local: Unidade de Cuidados Intensivos Polivalente (UCIP) de 16 camas. Métodos: Estudados doentes admitidos numa UCIP nos quais se avaliou a PVC em simultâneo com exame ETT que, para além da visualização da VCI, consistiu na obtenção da dimensão das cavidades cardíacas e função sistólica do ventrículo esquerdo. Para a correlação foram utilizados testes estatísticos paramétricos e não paramétricos. Resultados: Admitidos 560 doentes com registo simultâneo de PVC e ETT e incluídos 477 doentes em que foi possível visualizar a VCI, com idade média de 62,6 ± ±17,3 anos, média de internamento de 11,9 ± 18,7 dias, um índice APACHE II médio de 23,9 ± 8,9 e SAPS II médio de 55,7 ± 20,4. Por análise de regressão linear verificou-se uma relação entre a PVC e a dimensão máxima da VCI (p=0,013), o índice da VCI (p=0,001) e a presença de ventilação mecânica (p=0,002). A correlação linear entre a PVC e a dimensão máxima da VCI e respectivo índice foi de 0,34 e 0,44. Por teste de qui-quadrado, verificou-se uma relação estatisticamente significativa entre os seguintes intervalos de valores: índice da VCI 13 mmHg; índice da VCI entre 26 e 50% e PVC entre 8 e 12 mmHg; índice da VCI> 51% e PVC> 7 mmHg; dimensão máxima da VCI> 20 mmHg e PVC> 13 mmHg; dimensão máxima da VCI> 10 mm e PVC> 7 mmHg. Nos doentes com dilatação do ventrículo direito (VD) observou-se uma relação mais fraca entre a PVC 50%. A dimensão máxima da VCI, mas não o seu índice, correlacionou-se com a dilatação do VD e AD. Conclusões: A análise da VCI por ETT revelou-se útil na avaliação qualitativa da PVC em doentes admitidos numa UCIP. Em doentes com dilatação do VD e admitidos por exacerbação de doença pulmonar crónica, os métodos avaliados não foram fidedignos para valores baixos de PVC. A dilatação da VCI traduz melhor a cronicidade da doença, enquanto o índice da VCI reflecte melhor o estado de volemia. Key-words: Echocardiography, intensive care, central venous pressure, inferior vena cava, chronic respiratory failure, Palavras-chave: Pressão venosa central, ecocardiografia, cuidados intensivos, doença pulmonar crónica

a prospective study to determine the value of transthoracic echocardiography (TTE) in assessing hypotensive patients in a medical/surgical Intensive care Unit (ICU).a 16-bed medical/surgical ICU.patients with hypotension were studied (systolic arterial pressure < 90 mmHg or mean arterial pressure < 60 mmHg, non responsive to fluid therapy in a 30-minute period). TTE was aimed to: exclude severe cardiac dysfunction(abnormalities requiring immediate therapeutic decision); to evaluate other non severe cardiac alterations; to determine cardiac index (CI) and analyse inferior vena cava (IVC).Two hundred eight patients were studied, and 198 enrolled (4.5% of impossible examinations), with a mean age 63.4 +/- 16.2 years, 129 male, APACHE II score 30.1 +/- 9.9, SAPS II 68.8 +/- 20.5, SOFA 11.6 +/- 3.8, MODS 10.9 +/- 3.9. Mortality was 51% (n=101) and 168 (82.2%) patients were under mechanical ventilation. Forty four patients (44.4%) presented cardiac abnormalities, 28 of whom (14%) severe cardiac diseases. Of these, 18 (9%) presented unsuspected situations (aortic stenosis, 3; endocarditis, 4, dilated miocardiopathy, 9, cardiac tamponade, 2). Patients with cardiac abnormalities were older and presented higher severity scores and mortality. Most patients (158, 79.7%) presented a normal/high IC, all with low peripheral vascular resistance. Through logistic regression analysis, a statistically significant between IVC index and ICU stay (p=0.05); IC and IVC index correlated with overall mortality (p=0,008 and 0,041 respectively).Patients with hypotension in a medical/surgical ICU presented a high rate of cardiac abnormalities (44.4%, n=88), including 26 patients with severe diseases, requiring immediate therapeutic decisions. IC and IVC analysis may be useful to determine hemodynamic profile and several TTE parameters may have prognostic value.

Echocardiography is a valuable diagnostic tool allowing visualization of heart chambers for a complete anatomical and functional evaluation. In the past years there was a clear trend toward its use in other than cardiology areas, like intensive care and anesthesiology. In the Intensive Care its use is now widely accepted, as the concepts on hemodynamic monitoring evolved. This evolution is related to the criticism on pulmonary artery catheter use and its relation with both morbidity and mortality. The use of invasive diagnostic tools is therefore to be avoided but alternatives should also be available. Echocardiography equipment´s evolution toward better downsizing and lower price made the technique even more assessible in the past decade. The use of echocardiography offers the intensive care phisician a tool for a quick and comprehensive diagnosis of the critically ill; also, the examination is fast, does not require the involvement of other health personnel or disposable materials. The information is assessed in real time and obtained based on direct visualization of the heart. Specific issues for the intensive care are also studied using echocardiography. Among them is the sepsis related cardiomyopathy. In anesthesiology the use of echocardiography is quite established, especially in cardiac surgery monitoring. However echocardiography is also a valuable tool in non-cardiac surgery. The evaluation of volume status, left ventricular performance or right heart chambers monitorng are all significant information, not provided by other monitoring tools. The expanded use of echocardiography in non-cardiac surgery should be the next step in this evolution, and many anesthesiologists are using it. Specific monitoring protocols for specific situations must be implemented. The assessment of the patients on the emergency room using echocardiography is an area of growing interest. Contrast echocardiography is a good example. Although patients with suspected heart disease are more often evaluated, the possibilities of echocardiography go far beyond this type of patients. Many features of the approach used in the intensive care can be applied, as well as other potential uses beyond strict heart imaging. Echocardiography is now an image technique used by several non cardiologists specialists. A specific knowledge in this different settings is expected, emerging from its use in distinct disciplines.

The authors tested the feasibility of transthoracic echocardiography (TTE) as a routine technique in a medical/surgical ICU.

Acute renal failure in the critical care setting is a frequent and troublesome condition that can lead to significant morbidity and mortality. It is usually part of multiorgan failure with an expressive burden in the ICU.

Purple urine bag syndrome (PUBS) was first reported in 1978. PUBS is rare, occurs predominantly in constipated women, chronically catheterized and associated with some bacterial urinary infections that produce sulphatase/phosphatase. The etiology is due to indigo (blue) and indirubin (red) or to their mixture that becomes purple. A chain reaction begins in the gastrointestinal tract with tryptophan as described in the article.

The purpose of this letter is to emphasize some of the particular attributes of echocardiography, based on our experience over 20 years in its application in critically ill patients. In our opinion echocardiography is under-used, and its benefits can only truly be recognized if it is routinely applied as a diagnostic tool. In fact, it is a highly dynamic technique that permits direct visualization and assessment of all of the cardiac structures, as well as of the pulmonary artery and haemodynamic status. More than any other diagnostic tool, echocardiography allows detection of valvular disease; evaluation of systolic and diastolic function, and pericardial disease; and demonstration of intracardiac shunts and quantification thereof. Furthermore, one can calculate flows and pressures at various levels, study systole and diastole, and ultimately determine whether the data obtained are accurate, based on the dynamics of cardiac structures. Haemodynamic evaluation provides information in a just a few minutes, making it possible to initiate interventions immediately, at the level of volume repletion, cardiac contractility or peripheral resistance. Besides the primary cardiac entities (e.g. myocardial infarction, valvular disease and thrombi, etc.) that may benefit from echocardiographic evaluation, other cardiac abnormalities may also be revealed under stressful conditions. Among these, diastolic dysfunction deserves particular attention because it is quite common in those beyond middle age, and may assume great importance in a critically ill patient with sepsis, pneumonia or chronic respiratory disease. If undetected, it may determine the difference between life and death. Our group identified a highly significant correlation between the isovolumetric relaxation time (an important phase of diastole) and time of weaning from mechanical ventilation [1]. Other situations that are frequently encountered involve myocardium stunning, which may occur in diverse critical illnesses, as we mentioned before. Less common but no less important are right/left intracardiac shunts, which are often unsuspected and responsible for unexplained clinical deterioration in patients subjected to positive pressure ventilation. When a mechanically ventilated patient becomes more hypoxaemic despite efforts to improve ventilation, shunt-induced hypoxemia caused by a patent foramen ovale should be suspected, among other causes such as pulmonary embolism [2]. Only echocardiography can identify such specific abnormalities in mechanically ventilated patients, when weaning is difficult or refractory hypoxaemia is not explained by pulmonary disease alone. The main issue is that, globally, further knowledge and practice of echocardiography are required if we are to recognize its potential within the framework of general intensive care. Thus, our message is that we must first study patients using echo-cardiography, including clinical data, and then act accordingly. The contribution of echocardiography to the diagnosis and prompt treatment of many commonly overlooked situations may ultimately be associated with a decrease in morbidity and mortality. For this reason, we must promote training in echocardiography, as well as its routine use as an essential examination [3,4]. In our opinion, based on 20 years experience in echocardiography, the enormous advantages offered by this noninvasive technique renders it an indispensable tool in general intensive care units; consequently, training of physicians from specialities other than cardiology is required. Bluntly, it must become part of the intensivist's curriculum.