Antonio Paulo Nassar Junior

Terlipressin versus Norepinephrine in the Treatment of Hepatorenal Syndrome: A Systematic Review and Meta-Analysis

Background Hepatorenal syndrome (HRS) is a severe and progressive functional renal failure occurring in patients with cirrhosis and ascites. Terlipressin is recognized as an effective treatment of HRS, but it is expensive and not widely available. Norepinephrine could be an effective alternative. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of norepinephrine compared to terlipressin in the management of HRS. Methods We searched the Medline, Embase, Scopus, CENTRAL, Lilacs and Scielo databases for randomized trials of norepinephrine and terlipressin in the treatment of HRS up to January 2014. Two reviewers collected data and assessed the outcomes and risk of bias. The primary outcome was the reversal of HRS. Secondary outcomes were mortality, recurrence of HRS and adverse events. Results Four studies comprising 154 patients were included. All trials were considered to be at overall high risk of bias. There was no difference in the reversal of HRS (RR = 0.97, 95% CI = 0.76 to 1.23), mortality at 30 days (RR = 0.89, 95% CI = 0.68 to 1.17) and recurrence of HRS (RR = 0.72; 95% CI = 0.36 to 1.45) between norepinephrine and terlipressin. Adverse events were less common with norepinephrine (RR = 0.36, 95% CI = 0.15 to 0.83). Conclusions Norepinephrine seems to be an attractive alternative to terlipressin in the treatment of HRS and is associated with less adverse events. However, these findings are based on data extracted from only four small studies.

The use of sodium-chloride difference and chloride-sodium ratio as strong ion difference surrogates in the evaluation of metabolic acidosis in critically ill patients

PURPOSE Inorganic apparent strong ion difference (SIDai) improves chloride-associated acidosis recognition in dysnatremic patients. We investigated whether the difference between sodium and chloride (Na(+)-Cl(-)) or the ratio between chloride and sodium (Cl(-)/Na(+)) could be used as SIDai surrogates in mixed and dysnatremic patients. PATIENTS AND METHODS Two arterial blood samples were collected from 128 patients. Physicochemical analytical approach was used. Correlation, agreement, accuracy, sensitivity, and specificity were measured to examine whether Na(+)-Cl(-) and Cl(-)/Na(+) could be used instead of SIDai in the diagnosis of acidosis. RESULTS Na(+)-Cl(-) and Cl(-)/Na(+) were well correlated with SIDai (R = 0.987, P < 0.001 and R = 0.959, P < 0.001, respectively). Bias between Na(+)-Cl(-) and SIDai was high (6.384 with a limit of agreement of 4.463-8.305 mEq/L). Accuracy values for the identification of SIDai acidosis (<38.9 mEq/L) were 0.989 (95% confidence interval [CI], 0.980-0.998) for Na(+)-Cl(-) and 0.974 (95% CI, 0.959-0.989) for Cl(-)/Na(+). Receiver operator characteristic curve showed that values revealing SIDai acidosis were less than 32.5 mEq/L for Na(+)-Cl(-) and more than 0.764 for Cl(-)/Na(+) with sensitivities of 94.0% and 92.0% and specificities of 97.0% and 90.0%, respectively. Na(+)-Cl(-) was a reliable SIDai surrogate in dysnatremic patients. CONCLUSIONS Na(+)-Cl(-) and Cl(-)/Na(+) are good tools to disclose SIDai acidosis. In patients with dysnatremia, Na(+)-Cl(-) is an accurate tool to diagnose SIDai acidosis.

Aplicabilidade do escore fisiológico agudo simplificado (SAPS 3) em hospitais brasileiros

JUSTIFICATIVA E OBJETIVOS: O sistema prognostico SAPS 3 (Simplified Acute Physiology Score 3) e composto de 20 variaveis, representadas por escore fisiologico agudo e avaliacao do estado previo, visando estabelecer indice preditivo de mortalidade para pacientes admitidos em unidades de terapia intensiva (UTI). O estudo teve objetivo de validar este sistema e verificar o poder discriminatorio deste indice em pacientes cirurgicos do Brasil. METODO: Estudo prospectivo, realizado em duas UTI especializadas em pacientes cirurgicos de dois diferentes hospitais, no periodo de um ano, excluiuse pacientes com idade inferior a 16 anos, que permaneceram tempo inferior a 24 horas na UTI, readmitidos e aqueles admitidos para procedimento dialitico. A habilidade preditiva do indice SAPS 3 em diferenciar sobreviventes e nao sobreviventes foi verificada utilizando curva ROC e a calibracao pelo teste Hosmer-Lemeshow goodness-of-fit. RESULTADOS: Foram incluidos no estudo 1.310 pacientes. Operacoes gastrintestinais foram predominantes (34,9%). O menor valor do indice SAPS 3 foi 18 e o maior 154, media de 48,5 ± 18,1. A mortalidade hospitalar prevista e real foi de 10,3% e de 10,8%, respectivamente, razao de mortalidade padronizada (SMR) foi 1,04 (IC95% = 1,03-1,07). A calibracao pelo metodo Hosmer e Lemeshow mostrou X2 = 10,47 p = 0,234. O valor do escore SAPS 3 que melhor discriminou sobreviventes e nao sobreviventes foi 57, com sensibilidade de 75,8% e especificidade de 86%. Dos pacientes com indice SAPS 3 maior que 57, 73,5% nao sobreviveram versus 26,5% de sobreviventes (OR = 1,32 IC95% 1,23 - 1,42, p < 0,0001). CONCLUSOES: O sistema SAPS 3 e valido na populacao brasileira de pacientes cirurgicos, sendo util para indicar pacientes graves e determinar maiores cuidados neste grupo.

Applicability of the simplified acute physiology score (SAPS 3) in brazilian hospitals

BACKGROUND AND OBJECTIVES The SAPS 3 (Simplified Acute Physiology Score 3) prognostic system is composed of 20 parameters, represented by an acute physiology score and assessment of the previous status, aimed at establishing a predictive mortality index for patients admitted to intensive care units (ICU). The objective of this study was to validate this system and determine its discriminatory power in surgical patients in Brazil. METHODS This is a prospective study undertaken in two surgical ICUs of two different hospitals over a one-year period; patients younger than 16 years, who stay at the ICU for less than 24 hours, readmitted to the unit, and those admitted for dialysis were excluded from the study. The predictive ability of the SAPS 3 index to differentiate survivors and non-survivors was determined by the ROC curve and calibration by the Hosmer-Lemeshow goodness-of-fit test. RESULTS One thousand three-hundred and ten patients were included in the study. Gastrointestinal surgeries predominated (34.9%). Eighteen was the lower SAPS 3 index and the highest was 154, with a mean of 48.5 +/- 18.1. The predicted and real hospital mortality was 10.3% and 10.8%, respectively; the standardized mortality ratio (SMR) was 1.04 (95%CI = 1.03-1.07). Calibration by the Hosmer and Lemeshow method showed X(2) = 10.47 p = 0.234. The SAPS 3 score that better discriminated survivors and non-survivors was 57, with sensitivity of 75.8% and specificity 86%. Among the patients with SAPS 3 index higher than 57, 73.5% did not survive versus 26.5% who survived (OR= 1.32, 95%CI 1.23-1.42, p < 0.0001). CONCLUSIONS The SAPS 3 system is valid for the Brazilian population of surgical patients, being a useful indicator of critical patients and to determine greater care in this group.

Validity, reliability and applicability of Portuguese versions of sedation-agitation scales among critically ill patients

CONTEXT AND OBJECTIVE Sedation scales are used to guide sedation protocols in intensive care units (ICUs). However, no sedation scale in Portuguese has ever been evaluated. The aim of this study was to evaluate the validity and reliability of Portuguese translations of four sedation-agitation scales, among critically ill patients: Glasgow Coma Score, Ramsay, Richmond Agitation-Sedation Scale (RASS) and Sedation-Agitation Scale (SAS). DESIGN AND SETTING Validation study in two mixed ICUs of a university hospital. METHODS All scales were applied to 29 patients by four different critical care team members (nurse, physiotherapist, senior critical care physician and critical care resident). We tested each scale for interrater reliability and for validity, by correlations between them. Interrater agreement was measured using weighted kappa (k) and correlations used Spearmans test. RESULTS 136 observations were made on 29 patients. All scales had at least substantial agreement (weighted k 0.68-0.90). RASS (weighted k 0.82-0.87) and SAS (weighted k 0.83-0.90) had the best agreement. All scales had a good and significant correlation with each other. CONCLUSIONS All scales demonstrated good interrater reliability and were comparable. RASS and SAS showed the best correlations and the best agreement results in all professional categories. All these characteristics make RASS and SAS good scales for use at the bedside, to evaluate sedation-agitation among critically ill patients in terms of validity, reliability and applicability.

Daily sedative interruption versus intermittent sedation in mechanically ventilated critically ill patients: a randomized trial.

BackgroundDaily sedative interruption and intermittent sedation are effective in abbreviating the time on mechanical ventilation. Whether one is superior to the other has not yet been determined. Our aim was to compare daily interruption and intermittent sedation during the mechanical ventilation period in a low nurse staffing ICU.MethodsAdult patients expected to need mechanical ventilation for more than 24 hours were randomly assigned, in a single center, either to daily interruption of continuous sedative and opioid infusion or to intermittent sedation. In both cases, our goal was to maintain a Sedation Agitation Scale (SAS) level of 3 or 4; that is patients should be calm, easily arousable or awakened with verbal stimuli or gentle shaking. Primary outcome was ventilator-free days in 28 days. Secondary outcomes were ICU and hospital mortality, incidence of delirium, nurse workload, self-extubation and psychological distress six months after ICU discharge.ResultsA total of 60 patients were included. There were no differences in the ventilator-free days in 28 days between daily interruption and intermittent sedation (median: 24 versus 25 days, P = 0.160). There were also no differences in ICU mortality (40 versus 23.3%, P = 0.165), hospital mortality (43.3 versus 30%, P = 0.284), incidence of delirium (30 versus 40%, P = 0.472), self-extubation (3.3 versus 6.7%, P = 0.514), and psychological stress six months after ICU discharge. Also, the nurse workload was not different between groups, but it was reduced on day 5 compared to day 1 in both groups (Nurse Activity Score (NAS) in the intermittent sedation group was 54 on day 1 versus 39 on day 5, P < 0.001; NAS in daily interruption group was 53 on day 1 versus 38 on day 5, P < 0.001). Fentanyl and midazolam total dosages per patient were higher in the daily interruption group. The tidal volume was higher in the intermittent sedation group during the first five days of ICU stay.ConclusionsThere was no difference in the number of ventilator-free days in 28 days between both groups. Intermittent sedation was associated with lower sedative and opioid doses.Trial registrationClinicalTrials.gov Identifier: NCT00824239.

SAPS 3, APACHE IV or GRACE: which score to choose for acute coronary syndrome patients in intensive care units?

CONTEXT AND OBJECTIVE Acute coronary syndromes (ACS) are a common cause of intensive care unit (ICU) admission. Specific prognostic scores have been developed and validated for ACS patients and, among them, GRACE (Global Registry of Acute Coronary Events) has had the best performance. However, intensive care clinicians generally use prognostic scores developed from heterogeneous populations of critically ill patients, such as APACHE IV (Acute Physiologic and Chronic Health Evaluation IV) and SAPS 3 (Simplified Acute Physiology Score 3). The aim of this study was to evaluate and compare the performance of these three scores in a non-selected population of ACS cases. DESIGN AND SETTING Retrospective observational study to evaluate three prognostic scores in a population of ACS patients admitted to three general ICUs in private hospitals in São Paulo. METHODS All patients with ACS admitted from July 2008 to December 2009 were considered for inclusion in the study. Score calibration and discrimination were evaluated in relation to predicting hospital mortality. RESULTS A total of 1065 patients were included. The calibration was appropriate for APACHE IV and GRACE but not for SAPS 3. The discrimination was very good for all scores (area under curve of 0.862 for GRACE, 0.860 for APACHE IV and 0.804 for SAPS 3). CONCLUSIONS In this population of ACS patients admitted to ICUs, GRACE and APACHE IV were adequately calibrated, but SAPS 3 was not. All three scores had very good discrimination. GRACE and APACHE IV may be used for predicting mortality risk among ACS patients.

Caracterização físico-química da acidose metabólica induzida pela expansão volêmica inicial com solução salina a 0,9% em pacientes com sepse grave e choque séptico

OBJECTIVE: The aim of this study was to characterize and quantify metabolic acidosis that was caused by initial volume expansion during the reanimation of patients with severe sepsis and septic shock. METHODS: A blood sample was drawn for physicochemical characterization of the patients acid-base equilibrium both before and after volume expansion using 30 mL/kg 0.9% saline solution. The diagnosis and quantification of metabolic acidosis were based on the standard base excess (SBE). RESULTS: Eight patients with a mean age of 58 ± 13 years and mean APACHE II scores of 20 ± 4 were expanded using 2,000 ± 370 mL of 0.9% saline solution. Blood pH dropped from 7.404 ± 0.080 to 7.367 ± 0.086 (p=0.018), and PC O2 increased from 30 ± 5 to 32 ± 2 mmHg (p=0.215); SBE dropped from -4.4 ± 5.6 to -6.0 ± 5.7 mEq/L (p=0.039). The drop in SBE was associated with the acidifying power of two factors, namely, a significant increase in the strong ion gap (SIG) from 6.1 ± 3.4 to 7.7 ± 4.0 mEq/L (p = 0.134) and a non-significant drop in the apparent inorganic strong ion differences (SIDai) from 40 ± 5 to 38 ± 4 mEq/L (p = 0.318). Conversely, the serum albumin levels decreased from 3.1 ± 1.0 to 2.6 ± 0.8 mEq/L (p = 0.003) with an alkalinizing effect on SBE. Increased serum chloride levels from 103 ± 10 to 106 ± 7 mEq/L (p < 0.001) led to a drop in SIDai. CONCLUSION: Initial resuscitation using 30 mL/kg of 0.9% saline solution for patients with severe sepsis and septic shock is associated with worsened metabolic acidosis, as measured by SBE. This worsened SBE can be ascribed to a serum increase in the levels of unmeasurable anions and chloride.

Awaking, exercising, sitting, walking and extubating: moving on the paradigms for mechanically ventilated patients

In the intensive care unit (ICU) patients are exposed to catheters, tubes, alarms and noise, and they experience thirst, hunger, immobility and several other sources of discomfort. How hostile is the ICU environment to patients and to caregivers? It is intuitive to put patients to sleep while they stay in this inhospitable place for life support. Moreover, during sleep, respiration is controllable, oxygen consumption may be reduced, and patients’ appearances are placid to observers. Hibernation during critical illness was the gold standard of care for a long time.In 2000, Kress et al. showed that daily interruption of continuous sedation was associated with less time spent on mechanical ventilation and less time needing ICU support.

Is APACHE II a useful tool for clinical research

The population of patients admitted to the intensive care unit (ICU) is quite heterogeneous. Overall, the outcome of ICU treatment depends on the site, cause of admission, age, prior comorbidities, and acute physiological changes at admission and during the first several hours of treatment. Predictions of the in-hospital mortality of ICU patients play important roles with respect to inclusion/exclusion criteria in clinical trials, comparisons of observed mortality with predicted mortality using a score, and estimations of standardized mortality ratios in populations of critical patients. The need for such predictions has led many researchers to develop equations to calculate probabilities of associated mortality. Although prognostic scores have been used since the 1950s (such as the Apgar(1) score for newborns, which was developed by Virginia Apgar), their use for critically ill patients was established only in 1985, when Knaus et al. published the second version of the Acute Physiology and Chronic Health Evaluation (APACHE II),(2) which quickly became the most widely used prognostic index in ICUs and clinical trials worldwide. The original description of APACHE II is the most cited study in the intensive medicine literature to date.(3) The ability of a prognostic index to predict an outcome (in this case, inhospital mortality) is assessed based on its calibration and discrimination. Calibration refers to the correspondence between expected mortality predicted using the index and observed mortality in the examined population. Typically, calibration is evaluated by comparing observed and predicted mortality in given predicted risk groups (e.g., deciles, which are used in the Hosmer-Lemeshow test).(4) The calibration of a prognostic model generally deteriorates over time due to changes in ICU admission and discharge criteria, the evolution of support, and variations in the availability and effectiveness of different treatments for particular conditions. Thus, technological and scientific developments in intensive medicine over the last 30 years have rendered APACHE II obsolete. At present, this model generally overestimates mortality in many scenarios in which it is applied. Subsequent versions of this model, such as the most recent variant, APACHE IV,(5) correct this problem, at least in part. As described by Soares et al.,(6) APACHE II should not be used as a benchmarking tool in the ICU because almost any ICU today would be considered “high performance” based on having hospital mortality much lower than that expected in 1985. Rui P. Moreno1, Antonio Paulo Nassar Jr.2