RESUMO
BACKGROUND: Advanced glycation end products (AGEs) have been implicated in multiple organ failure, predominantly via their cellular receptor (RAGE) in preclinical studies. Little is known about the time course and prognostic relevance of AGEs in critically ill human patients, including those with severe sepsis. OBJECTIVE: 1) To explore the reliability of Skin Autofluorescence (AF) as an index of tissue AGEs in ICU patients, 2) to compare its levels to healthy controls, 3) to describe the time course of AGEs and influencing factors during ICU admission, and 4) to explore their association with disease severity, outcome, and markers of oxidative stress and inflammation. METHODS: Skin AF, serum N"-(carboxyethyl)lysine (CEL), N"-(carboxymethyl)lysine (CML), and soluble RAGE (sRAGE) were serially measured for a maximum of 7 days in critically ill ICU patients with multiple organ failure and compared to age-matched healthy controls. Correlations with (changes in) clinical parameters of disease severity, LDL dienes, and CRP were studied and survival analysis for in-hospital mortality was performed. RESULTS: Forty-five ICU patients (age: 59±15 years; 60% male), and 37 healthy controls (59±14; 68%) were included. Skin AF measurements in ICU patients were reproducible (CV right-left arm: 13%, day-to-day: 10%), with confounding effects of skin reflectance and plasma bilirubin levels. Skin AF was higher in ICU patients vs healthy controls (2.7±0.7 vs 1.8±0.3 au; p<0.001). Serum CEL (23±10 vs, 16±3 nmol/gr protein; p<0.001), LDL dienes (19 (15-23) vs. 9 (8-11) µmol/mmol cholesterol; <0.001), and sRAGE (1547 (998-2496) vs. 1042 (824-1388) pg/ml; p = 0.003) were significantly higher in ICU patients compared to healthy controls, while CML was not different (27 (20-39) vs 29 (25-33) nmol/gr protein). While CRP and LDL dienes decreased significantly, Skin AF and serum AGEs and sRAGE did not change significantly during the first 7 days of ICU admission. CML and CEL were strongly correlated with SOFA scores and CML above the median at baseline was associated with increased risk for mortality (Hazard ratio 3.3 (1.3-8.3); p = 0.01). All other markers did not correlate with disease severity and did not predict mortality. CONCLUSIONS: This study demonstrates that markers for the AGE-RAGE axis are elevated in critically ill patients compared to healthy controls but remain stable for at least 7 days despite clearly fading inflammation and oxidative stress. Circulating AGEs may be associated with disease severity and outcome. Further research should be conducted to elucidate the role of the AGE-RAGE axis in the exaggerated inflammatory response leading to multiple organ failure and death, and whether or not this may be a target for treatment.
Assuntos
Estado Terminal/mortalidade , Produtos Finais de Glicação Avançada/metabolismo , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Estresse Oxidativo , Admissão do Paciente , Pele/metabolismo , Bilirrubina/sangue , Biomarcadores/sangue , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Feminino , Produtos Finais de Glicação Avançada/sangue , Humanos , Inflamação/sangue , Inflamação/metabolismo , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Receptor para Produtos Finais de Glicação Avançada/metabolismoRESUMO
OBJECTIVE: To assess whether cardiac abnormalities after aneurysmal subarachnoid hemorrhage (aSAH) are associated with delayed cerebral ischemia (DCI) and clinical outcome, independent from known clinical risk factors for these outcomes. METHODS: In a prospective, multicenter cohort study, we performed echocardiography and ECG and measured biochemical markers for myocardial damage in patients with aSAH. Outcomes were DCI, death, and poor clinical outcome (death or dependency for activities of daily living) at 3 months. With multivariable Poisson regression analysis, we calculated risk ratios (RRs) with corresponding 95% confidence intervals. We used survival analysis to assess cumulative percentage of death in patients with and without echocardiographic wall motion abnormalities (WMAs). RESULTS: We included 301 patients with a mean age of 57 years; 70% were women. A wall motion score index ≥1.2 had an adjusted RR of 1.2 (0.9-1.6) for DCI, 1.9 (1.1-3.3) for death, and 1.8 (1.1-3.0) for poor outcome. Midventricular WMAs had adjusted RRs of 1.1 (0.8-1.4) for DCI, 2.3 (1.4-3.8) for death, and 2.2 (1.4-3.5) for poor outcome. For apical WMAs, adjusted RRs were 1.3 (1.1-1.7) for DCI, 1.5 (0.8-2.7) for death, and 1.4 (0.8-2.5) for poor outcome. Elevated troponin T levels, ST-segment changes, and low voltage on the admission ECGs had a univariable association with death but were not independent predictors for outcome. CONCLUSION: WMAs are independent risk factors for clinical outcome after aSAH. This relation is partly explained by a higher risk of DCI. Further study should aim at treatment strategies for these aSAH-related cardiac abnormalities to improve clinical outcome.
Assuntos
Cardiopatias/etiologia , Hemorragia Subaracnóidea/complicações , Adulto , Idoso , Estudos de Coortes , Ecocardiografia , Feminino , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Cardiopatias/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Países Baixos , Razão de Chances , Fatores de Risco , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/mortalidade , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and - despite many unanswered questions - therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting multiple mechanisms at the same time, have appeared to be beneficial. We clearly need to understand better the mechanisms that underlie MODS. The endothelium certainly plays an active role in MODS. It functions at the intersection of several systems, including inflammation, coagulation, haemodynamics, fluid and electrolyte balance, and cell migration. An important regulator of these systems is the angiopoietin/Tie2 signalling system. In this review we describe this signalling system, giving special attention to what is known about it in critically ill patients and its potential as a target for therapy.
Assuntos
Angiopoietina-2/metabolismo , Estado Terminal , Insuficiência de Múltiplos Órgãos/metabolismo , Transdução de Sinais , Humanos , Insuficiência de Múltiplos Órgãos/fisiopatologiaRESUMO
For severe lithium intoxication haemodialysis is recommended to lower serum lithium levels rapidly. Frequently, serum lithium levels rebound after dialysis and repeated dialysis is needed. This is the first report of an adult patient with severe lithium intoxication who underwent haemodialysis (HD) followed by continuous veno-venous haemodiafiltration (CVVHDF). Mean lithium clearances with HD and CVVHDF were 173 and 61 ml/min, respectively. Serum lithium levels were rapidly lowered and did not rebound. Two compartment simulations illustrate that HD followed by CVVHDF is the most effective strategy for removing lithium from the intracellular compartment.
Assuntos
Antidepressivos/intoxicação , Transtorno Depressivo/tratamento farmacológico , Hemofiltração , Compostos de Lítio/intoxicação , Modelos Biológicos , Diálise Renal , Idoso de 80 Anos ou mais , Antidepressivos/sangue , Antidepressivos/farmacocinética , Compartimentos de Líquidos Corporais , Feminino , Humanos , Compostos de Lítio/sangue , Compostos de Lítio/farmacocinéticaRESUMO
Amiodarone is considered a first-choice antiarrhythmic drug in critically ill patients with new-onset atrial fibrillation (AF). However, evidence supporting the use of this potentially toxic drug in critically ill patients is scarce. Magnesium sulphate (MgSO4) has shown to be effective for both rate and rhythm control, to act synergistically with antiarrhythmic drugs, and to prevent proarrhythmia. Treatment with MgSO4 may reduce the need for antiarrhythmic drugs such as amiodarone in critically ill patients with new-onset atrial fibrillation. The efficacy of a new institutional protocol was evaluated. Patients were treated with a new institutional protocol for new-onset atrial fibrillation in critically ill patients. An MgSO4 bolus (0.037 g/kg body weight in 15 minutes) was followed by continuous infusion (0.025 g/kg body weight/h). Intravenous amiodarone (loading dose 300 mg, followed by continuous infusion of 1200 mg/24 h) was given to those not responding to MgSO4 within 1 hour. Clinical response was defined as conversion to sinus rhythm or decrease in heart rate <110 beats/min. Sixteen of the 29 patients responded to MgSO4 monotherapy, whereas the addition of amiodarone was needed in 13 patients. Median (range) time until conversion to sinus rhythm after MgSO4 was 2 (1-45) hours. Median (range) conversion time in patients requiring amiodarone was 4 (2-78) hours, and median (range) conversion time in all patients was 3 (1-78) hours. The 24-hour conversion rate was 90%. Relapse atrial fibrillation was seen in 7 patients. The magnesium-amiodarone step-up scheme reduces the need for amiodarone, effectively converts new-onset atrial fibrillation into a sinus rhythm within 24 hours, and seems to be safe in critically ill patients.
Assuntos
Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Estado Terminal , Sulfato de Magnésio/administração & dosagem , Idoso , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Estudos ProspectivosAssuntos
Antidepressivos de Segunda Geração/intoxicação , Cicloexanóis/intoxicação , Hipoglicemia/induzido quimicamente , Adulto , Antídotos/uso terapêutico , Glicemia/metabolismo , Carvão Vegetal/uso terapêutico , Creatina Quinase/sangue , Cuidados Críticos , Transtorno Depressivo/complicações , Transtorno Depressivo/psicologia , Escala de Coma de Glasgow , Humanos , Hipnóticos e Sedativos/intoxicação , Masculino , Oxazepam/intoxicação , Respiração Artificial , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/psicologia , Tentativa de Suicídio , Cloridrato de VenlafaxinaAssuntos
Glicemia/metabolismo , Hiperglicemia/economia , Insulina/economia , Unidades de Terapia Intensiva/economia , Tempo de Internação/economia , Análise Custo-Benefício , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/mortalidade , Insulina/uso terapêutico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: To obtain strict glucose regulation, an accurate and feasible bedside glucometry method is essential. We evaluated three different types of point-of-care glucometry in seriously ill intensive care unit (ICU) patients. The study was performed as a single-centre, prospective, observational study in a 12-bed medical ICU of a university hospital. METHODS: Patients with an expected ICU stay of more than 48 hours were included. Because the reference laboratory delivers glucose values after approximately 30 to 60 minutes, which is too slow to use in a glucose regulation protocol and for calibration of the subcutaneous continuous glucose monitoring system (CGMS) (CGMS System Gold), we first validated the ICU-based blood gas/glucose analyser ABL715 (part 1 of the study). Subsequently, part 2 was performed: after inserting (and calibrating) the subcutaneous CGMS, heparinised arterial blood samples were drawn from an arterial line every 6 hours and analysed on both the Precision PCx point-of-care meter using test strips and on the blood gas/glucose analyser ABL715. CGMS glucose data were downloaded after 24 to 72 hours. The results of the paired measurements were analysed as a scatter plot by the method of Bland and Altman and were expressed as a correlation coefficient. RESULTS: Part 1: Four hundred and twenty-four blood samples were drawn from 45 critically ill ICU patients. The ICU-based blood gas/glucose analyser ABL715 provided a good estimate of conventional laboratory glucose assessment: the correlation coefficient was 0.95. In the Clarke error grid, 96.8% of the paired measurements were in the clinically acceptable zones A and B. Part 2: One hundred sixty-five paired samples were drawn from 19 ICU patients. The Precision PCx point-of-care meter showed a correlation coefficient of 0.89. Ninety-eight point seven percent of measurements were within zones A and B. The correlation coefficient for the subcutaneous CGMS System Gold was 0.89. One hundred percent of measurements were within zones A and B. CONCLUSION: The ICU-based blood glucose analyser ABL715 is a rapid and accurate alternative for laboratory glucose determination and can serve as a standard for ICU blood glucose measurements. The Precision PCx is a good alternative, but feasibility may be limited because of the blood sample handling. The subcutaneous CGMS System Gold is promising, but real-time glucose level reporting is necessary before it can be of clinical use in the ICU. When implementing a glucose-insulin algorithm in patient care or research, one should realise that the absolute glucose level may differ systematically among various measuring methods, influencing targeted glucose levels.
Assuntos
Glicemia/análise , Estado Terminal/epidemiologia , Unidades de Terapia Intensiva , Sistemas Automatizados de Assistência Junto ao Leito , Adulto , Idoso , Estudos de Viabilidade , Humanos , Unidades de Terapia Intensiva/normas , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Sistemas Automatizados de Assistência Junto ao Leito/normas , Sensibilidade e EspecificidadeAssuntos
Infecções por Vírus Epstein-Barr/complicações , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Insuficiência de Múltiplos Órgãos/etiologia , Adolescente , Antibacterianos/uso terapêutico , Humanos , Mononucleose Infecciosa/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Insuficiência de Múltiplos Órgãos/diagnósticoRESUMO
Imported falciparum malaria is increasing in Western countries. In patients with severe disease, exchange transfusion has been added to antimalarial and conventional supportive therapy to increase removal of parasitized erythrocytes, but hemodynamic compromise limits its use; automated erythrocytapheresis may be advantageous. We review published reports of patients with severe falciparum malaria treated by automated erythrocytapheresis combined with standard therapy and add three more cases to the literature. No studies have been conducted to evaluate its clinical efficacy, and this adjunct therapy should therefore be considered as salvage therapy. Apheresis of red cells appears feasible, safe and effective in rapidly reducing parasite count.
Assuntos
Eritrócitos , Transfusão Total , Malária Falciparum/terapia , HumanosRESUMO
We describe the cases of two patients discharged home directly from the ICU. Both patients had the strong wish to die at home after being told that there were no therapeutic options. Sometimes discharge is feasible and can mean very much for patients and their family. Taking measures to ensure a "good deathbed" is an obligation for doctors and nursing staff. However, due to the focus on cure this palliative goal is not always pursued.
Assuntos
Morte , Assistência Domiciliar , Satisfação do Paciente , Feminino , Humanos , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , Países BaixosRESUMO
INTRODUCTION: Tight glycaemic control is an important issue in the management of intensive care unit (ICU) patients. The glycaemic goals described by Van Den Berghe and colleagues in their landmark study of intensive insulin therapy appear difficult to achieve in a real life ICU setting. Most clinicians and nurses are concerned about a potentially increased frequency of severe hypoglycaemic episodes with more stringent glycaemic control. One of the steps we took before we implemented a glucose regulation protocol was to review published trials employing insulin/glucose algorithms in critically ill patients. METHODS: We conducted a search of the PubMed, Embase and Cochrane databases using the following terms: 'glucose', 'insulin', 'protocol', 'algorithm', 'nomogram', 'scheme', 'critically ill' and 'intensive care'. Our search was limited to clinical trials conducted in humans. The aim of the papers selected was required to be glycaemic control in critically ill patients; the blood glucose target was required to be 10 mmol/l or under (or use of a protocol that resulted in a mean blood glucose = 10 mmol/l). The studies were categorized according to patient type, desired range of blood glucose values, method of insulin administration, frequency of blood glucose control, time taken to achieve the desired range for glucose, proportion of patients with glucose in the desired range, mean blood glucose and frequency of hypoglycaemic episodes. RESULTS: A total of twenty-four reports satisfied our inclusion criteria. Most recent studies (nine) were conducted in an ICU; nine others were conducted in a perioperative setting and six were conducted in patients with acute myocardial infarction or stroke. Studies conducted before 2001 did not include normoglycaemia among their aims, which changed after publication of the study by Van Den Berghe and coworkers in 2001; glycaemic goals became tighter, with a target range between 4 and 8 mmol/l in most studies. CONCLUSION: Studies using a dynamic scale protocol combining a tight glucose target and the last two blood glucose values to determine the insulin infusion rate yielded the best results in terms of glycaemic control and reported low frequencies of hypoglycaemic episodes.
Assuntos
Algoritmos , Glicemia/metabolismo , Estado Terminal , Hipoglicemia/sangue , Glicemia/efeitos dos fármacos , Estado Terminal/epidemiologia , Estudos de Viabilidade , Humanos , Hipoglicemia/tratamento farmacológico , Insulina/administração & dosagemRESUMO
OBJECTIVE: The Brugada syndrome is a clinical and electrocardiographic familial entity, which may lead to sudden cardiac death. A Brugada pattern ECG may occasionally be caused by conditions such as an overdose of tricyclic antidepressants (TCA). Toxicity of TCA frequently results in the need for critical care support. We retrospectively studied characteristics and electrocardiographic indicators of toxicity of all TCA poisoned patients. SETTING: All patients admitted from 1/1/2000 to 1/11/2004 to our ICU after an act of deliberate self-poisoning were included. The ECG's were analysed retrospectively by a cardiologist. Patients with an overdose of TCA were divided in three groups; I. without ECG abnormalities, II. Presence of ECG abnormalities but without Brugada signs, III patients with a Brugada pattern ECG. RESULTS: 134 patients were admitted. In 35 patients a TCA was the main toxic substance. In 12 (34%) TCA patients no ECG abnormalities were found. An increase in QRS duration (>100 ms) was seen in 13 (37%) cases. Six (17%) of them demonstrated a Brugada like pattern. The ECG abnormalities resolved quickly after administration of sodium bicarbonate. Length of stay did not differ between groups. APACHE II and the amount of sodium bicarbonate administered were the highest in the Brugada pattern group. Two patients died. CONCLUSIONS: in TCA poisoning the Brugada pattern ECG is a particular manifestation of the frequently occurring intraventricular conduction disturbances. In intoxicated patients in whom the substance is unknown early recognition of the conduction disturbances is important for suspecting a poisoning with TCA.