Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU).

PURPOSE: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42). CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

Septic shock 3.0 criteria application in severe COVID-19 patients: An unattended sepsis population with high mortality risk.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can be associated with life-threatening organ dysfunction due to septic shock, frequently requiring intensive care unit (ICU) admission, respiratory and vasopressor support. Therefore, clear clinical criteria are pivotal for early recognition of patients more likely to need prompt organ support. Although most patients with severe COVID-19 meet the Sepsis-3.0 criteria for septic shock, it has been increasingly recognized that hyperlactatemia is frequently absent, possibly leading to an underestimation of illness severity and mortality risk. AIM: To identify the proportion of severe COVID-19 patients with vasopressor support requirements, with and without hyperlactatemia, and describe their clinical outcomes and mortality. METHODS: We performed a single-center prospective cohort study. All adult patients admitted to the ICU with COVID-19 were included in the analysis and were further divided into three groups: Sepsis group, without both criteria; Vasoplegic Shock group, with persistent hypotension and vasopressor support without hyperlactatemia; and Septic Shock 3.0 group, with both criteria. COVID-19 was diagnosed using clinical and radiologic criteria with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR test. RESULTS: 118 patients (mean age 63 years, 87% males) were included in the analysis (n = 51 Sepsis group, n = 26 Vasoplegic Shock group, and n = 41 Septic Shock 3.0 group). SOFA score at ICU admission and ICU length of stay were different between the groups (P < 0.001). Mortality was significantly higher in the Vasoplegic Shock and Septic Shock 3.0 groups when compared with the Sepsis group (P < 0.001) without a significant difference between the former two groups (P = 0.713). The log rank tests of Kaplan-Meier survival curves were also different (P = 0.007). Ventilator-free days and vasopressor-free days were different between the Sepsis vs Vasoplegic Shock and Septic Shock 3.0 groups (both P < 0.001), and similar in the last two groups (P = 0.128 and P = 0.133, respectively). Logistic regression identified the maximum dose of vasopressor therapy used (AOR 1.046; 95%CI: 1.012-1.082, P = 0.008) and serum lactate level (AOR 1.542; 95%CI: 1.055-2.255, P = 0.02) as the major explanatory variables of mortality rates (R 2 0.79). CONCLUSION: In severe COVID-19 patients, the Sepsis 3.0 criteria of septic shock may exclude approximately one third of patients with a similarly high risk of a poor outcome and mortality rate, which should be equally addressed.

Predictive value of D-dimer in the clinical outcome of severe COVID19 patients: Are we giving it too much credit?

BACKGROUND: COVID-19 is a new form of acute respiratory failure leading to multiorgan failure and ICU admission. Gathered evidence suggests that a 3-fold rise in D-dimer concentrations may be linked to poor prognosis and higher mortality. PURPOSE: To describe D-dimer admission profile in severe ICU COVID19 patients and its predictive role in outcomes and mortality. METHODS: Single-center retrospective cohort study. All adult patients admitted to ICU with COVID19 were divided into 3 groups: (1) Lower-values group (D-dimer levels < 3-fold normal range value [NRV] [500ng/mL]), Intermediate-values group (D-dimer ≥3-fold and <10-fold NRV) and Higher-value group (≥10-fold NRV). RESULTS: 118 patients (mean age 63 years, 73% males) were included (N = 73 Lower-values group, N = 31 Intermediate-values group; N = 11 Higher-values group). Mortality was not different between groups (p = 0.51). Kaplan-Meier survival curves revealed no differences (p = 0.52) between groups, nor it was verified even when gender, age, ICU length of stay, and SOFA score were considered as covariables. CONCLUSIONS: In severe COVID19 patients, the D-dimer profile does not retain a predictive value regarding patients' survivability and should not be used as a surrogate of disease severity.

Association of Iron Supplementation Programs with Iron-Deficiency Anemia Outcomes among Children in Brazil.

Anemia remains a condition with high prevalence in populations worldwide, and the prevalence of anemia among children under five years old in Brazil is approximately 40%, being higher in communities marked by social inequities. Diverse government programs during recent decades targeted iron-deficiency anemia, considering its impacts throughout the lifetime. The objective of this study was to investigate the effects of two government iron supplementation programs on health outcomes related to iron-deficiency anemia among children up to 4 years old in Brazilian municipalities. A longitudinal panel encompassing data from 5570 municipalities from 1998 to 2019 was investigated using a difference-in-differences framework with multiple interventions and distinct times of adhesion, and fixed-effects models were estimated to control for invariant municipal characteristics throughout the period in order to ensure comparability. The results indicate significant effects of the federal programs in reducing hospitalizations and lengths of stay due to iron-deficiency anemia, especially in non-poor municipalities. There was complementarity in the effects of the programs; however, neither of the programs influenced mortality rates. Thus, it is important to consider possible improvements in the operationalization of the programs, in order to achieve better results in the reduction of severe iron-deficiency anemia among children up to 4 years old.

Respiratory viruses in mechanically ventilated patients: a pilot study.

BACKGROUND: Respiratory virome is an integral part of the human microbiome and its characterization may contribute to a better understanding of the changes that arise in the disease and, consequently, influence the approach and treatment of patients with acute lower respiratory infections. The aim of this study was to evaluate the presence of respiratory viruses in the lower airways of individuals undergoing invasive mechanical ventilation, with and without acute lower respiratory infection (respectively WRI and WORI groups). METHODS: We studied 44 mini-bronchoalveolar lavage samples (collected with a double catheter, Combicath® kit) from patients with mean age in the seventh decade, 20 from WORI group and 24 from WRI group, who were hospitalized for acute respiratory failure in Intensive Care Units of two hospitals in the Lisbon area. Real-time PCR was applied to verify analyse the presence of 15 common respiratory viruses (adenovirus, human bocavirus, influenza virus A and B, repiratory syncytial virus, human parainfluenza virus types 1, 2, 3 and 4, human enterovirus, human rhinovirus, human metapneumovirus, human coronavirus group 1 (229E, NL63) and 2 (OC43, HKU1). RESULTS: Respiratory viruses were detected in six of the 20 patients in the WORI group: influenza AH3 (n = 2), parainfluenza virus 1/3 (n = 2), human rhinovirus (n = 2), respiratory syncytial virus (n = 1) and human metapneumovirus (n = 1). In the WRI group, respiratory viruses were detected in 12 of the 24 patients: influenza AH3 (n = 3), human rhinovirus (n = 3), respiratory syncytial virus (n = 3), human metapneumovirus (n = 3), human bocavirus (n = 2) and human enterovirus (n = 1). Simultaneous detection of two viruses was recorded in two samples in both groups. CONCLUSIONS: The results of this study suggest the presence of common respiratory viruses in the lower respiratory tract without causing symptomatic infection, even in carefully collected lower samples. This may have important implications on the interpretation of the results on the diagnostic setting.

Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study.

BACKGROUND: Ventilator-associated tracheobronchitis has been suggested as an intermediate process between tracheobronchial colonisation and ventilator-associated pneumonia in patients receiving mechanical ventilation. We aimed to establish the incidence and effect of ventilator-associated tracheobronchitis in a large, international patient cohort. METHODS: We did a multicentre, prospective, observational study in 114 intensive care units (ICU) in Spain, France, Portugal, Brazil, Argentina, Ecuador, Bolivia, and Colombia over a preplanned time of 10 months. All patients older than 18 years admitted to an ICU who received invasive mechanical ventilation for more than 48 h were eligible. We prospectively obtained data for incidence of ventilator-associated lower respiratory tract infections, defined as ventilator-associated tracheobronchitis or ventilator-associated pneumonia. We grouped patients according to the presence or absence of such infections, and obtained data for the effect of appropriate antibiotics on progression of tracheobronchitis to pneumonia. Patients were followed up until death or discharge from hospital. To account for centre effects with a binary outcome, we fitted a generalised estimating equation model with a logit link, exchangeable correlation structure, and non-robust standard errors. This trial is registered with ClinicalTrials.gov, number NCT01791530. FINDINGS: Between Sept 1, 2013, and July 31, 2014, we obtained data for 2960 eligible patients, of whom 689 (23%) developed ventilator-associated lower respiratory tract infections. The incidence of ventilator-associated tracheobronchitis and that of ventilator-associated pneumonia at baseline were similar (320 [11%; 10·2 of 1000 mechanically ventilated days] vs 369 [12%; 8·8 of 1000 mechanically ventilated days], p=0·48). Of the 320 patients with tracheobronchitis, 250 received appropriate antibiotic treatment and 70 received inappropriate antibiotics. 39 patients with tracheobronchitis progressed to pneumonia; however, the use of appropriate antibiotic therapy for tracheobronchitis was associated with significantly lower progression to pneumonia than was inappropriate treatment (19 [8%] of 250 vs 20 [29%] of 70, p<0·0001; crude odds ratio 0·21 [95% CI 0·11-0·41]). Significantly more patients with ventilator-associated pneumonia died (146 [40%] of 369) than those with tracheobronchitis (93 [29%] of 320) or absence of ventilator-associated lower respiratory tract infections (673 [30%] of 2271, p<0·0001). Median time to discharge from the ICU for survivors was significantly longer in the tracheobronchitis (21 days [IQR 15-34]) and pneumonia (22 [13-36]) groups than in the group with no ventilator-associated lower respiratory tract infections (12 [8-20]; hazard ratio 1·65 [95% CI 1·38-1·97], p<0·0001). INTERPRETATION: This large database study emphasises that ventilator-associated tracheobronchitis is a major health problem worldwide, associated with high resources consumption in all countries. Our findings also show improved outcomes with use of appropriate antibiotic treatment for both ventilator-associated tracheobronchitis and ventilator-associated pneumonia, underlining the importance of treating both infections, since inappropriate treatment of tracheobronchitis was associated with a higher risk of progression to pneumonia. FUNDING: None.

What do we know about carbon monoxide poisoning and cardiac compromise?

Carbon monoxide (CO) poisoning is one of the most common types of poisoning and the leading cause of death by poisoning worldwide. Cardiac injury caused by CO poisoning has been little described despite being a predictor of poor prognosis. We present the case of a healthy 24-year-old woman, admitted to our emergency room due to an episode of lipothymia without loss of consciousness. She reported holocranial headache for the previous two weeks associated with nausea and vomiting. Laboratory tests revealed blood gas analysis: pH 7.392, pCO2 32 mmHg, pO2 101 mmHg, lactate 3.5 mmol/l, HCO3 20.8 mmol/l; COHb 29.2%; serial troponin I 1.21 → 5.25 → 6.13 → 3.65 µg/l; myoglobin 1378 → 964 → 352 µg/l; and NT-proBNP 1330 pg/l. The electrocardiogram showed sinus rhythm, heart rate 110 bpm, and ST-segment depression of 2 mm in V4 and 1 mm in V5. Transthoracic echocardiography revealed a left ventricle with normal wall motion and preserved ejection fraction. Given the clinical and epidemiological context, myocardial and central nervous system ischemia due to prolonged CO exposure was assumed and normobaric oxygen therapy was immediately started. In view of evidence of injury to two major organ systems the indication for hyperbaric oxygen therapy was discussed with a specialist colleague, who suggested maintaining conservative treatment with oxygen therapy and in-hospital monitoring for 72 h. The patient was discharged on the third day and was still asymptomatic at 400 days of follow-up. Besides symptoms and signs of central nervous system dysfunction, myocardial damage should also always be considered in the context of CO poisoning. Hyperbaric therapy is still controversial and the lack of objective data highlights the need for new randomized studies.

Continuous infusion of piperacillin/tazobactam in septic critically ill patients--a multicenter propensity matched analysis.

The clinical efficacy of continuous infusion of piperacillin/tazobactam in critically ill patients with microbiologically documented infections is currently unknown. We conducted a retrospective multicenter cohort study in 7 Portuguese intensive care units (ICU). We included 569 critically ill adult patients with a documented infection and treated with piperacillin/tazobactam admitted to one of the participating ICU between 2006 and 2010. We successfully matched 173 pairs of patients according to whether they received continuous or conventional intermittent dosing of piperacillin/tazobactam, using a propensity score to adjust for confounding variables. The majority of patients received 16g/day of piperacillin plus 2g/day of tazobactam. The 28-day mortality rate was 28.3% in both groups (p = 1.0). The ICU and in-hospital mortality were also similar either in those receiving continuous infusion or intermittent dosing (23.7% vs. 20.2%, p = 0.512 and 41.6% vs. 40.5%, p = 0.913, respectively). In the subgroup of patients with a Simplified Acute Physiology Score (SAPS) II>42, the 28-day mortality rate was lower in the continuous infusion group (31.4% vs. 35.2%) although not reaching significance (p = 0.66). We concluded that the clinical efficacy of piperacillin/tazobactam in this heterogeneous group of critically ill patients infected with susceptible bacteria was independent of its mode of administration, either continuous infusion or intermittent dosing.

Papel neuroprotector da hipotermia terapêutica pós paragem cardio-respiratória / The neuroprotective role of therapeutic hypothermia after cardiac arrest

OBJECTIVOS: A hipotermia terapêutica demonstrou ter efeitos neuro e cardioprotectores, com melhoria da sobrevida e redução das sequelas neurológicas em doentes vítimas de paragem cardio-respiratória. O objectivo deste estudo foi avaliar a evolução dos doentes submetidos a hipotermia terapêutica após paragem cardio-respiratória. MÉTODOS: Estudo prospectivo observacional dos doentes submetidos a hipotermia terapêutica após paragem cardio-respiratória numa unidade de cuidados intensivos polivalente durante 10 meses. Aos doentes admitidos até 12 horas após paragem cardio-respiratória foi induzida a hipotermia terapêutica através da administração de fluidos arrefecidos e arrefecimento corporal externo e mantida a temperatura alvo, 33°C, durante 24 horas. RESULTADOS: Foram incluídos 12 doentes, idade (mediana) de 64 anos, 58 por cento do sexo masculino. A paragem cardio-respiratória ocorreu em meio hospitalar em 6 doentes. O índice de Charlson, o Sequential Organ Failure Assessment (SOFA) e o Acute Physiology and Chronic Health Evaluation II, no primeiro dia, foram 2.9 [IIQ 6.8], 11 [IIQ 2.75], e 24.5 [IIQ 15.25], respectivamente. A taxa de mortalidade na unidade de cuidados intensivos polivalente foi de 42 por cento (N=5). Dos 7 sobreviventes, 5 recuperaram o estado neurológico prévio à paragem cardio-respiratória. A hipotermia terapêutica foi iniciada cerca de 120 minutos [IIQ 78.75], após recuperação de circulação espontânea. A maioria dos doentes (75 por cento) necessitou de suporte vasopressor. Foi constatado, nos 3 dias subsequentes à paragem cardio-respiratória e hipotermia terapêutica, uma diminuição do valor mediano de SOFA (11[IIQ 2.75], no dia 0, 10 [IIQ 3], no dia 1 e 7 [IIQ 4.5], no dia 2). CONCLUSÃO: A aplicação de um protocolo de hipotermia terapêutica revelou ser simples e eficaz e permitiu obter em doentes com indicação, boa recuperação neurológica.

OBJECTIVES: Therapeutic hypothermia following cardiorespiratory arrest has been demonstrated to have cardio- and neuroprotective effects, resulting in improved survival and better neurological outcomes. The objective of this study was to assess the outcomes of patients undergoing therapeutic hypothermia following cardiorespiratory arrest. METHODS: A prospective, 10-month observational study of patients admitted to an intensive care unit and undergoing therapeutic hypothermia after cardiorespiratory arrest was undertaken. Therapeutic hypothermia was induced by cold fluid administration and body surface cooling in patients admitted no more than 12 hours after resuscitation from cardiorespiratory arrest. A target temperature of 33ºC was maintained for 24 hours. RESULTS: Overall, 12 patients were included (median age 64 years, 58 percent male). Half of the cardiorespiratory arrests were in-hospital. The median first-day Charlson Index, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II scores were of 2.9, 11 and 24.5, respectively. The intensive care unit mortality rate was 42 percent (N=5). Five of the 7 surviving patients recovered their pre-cardiorespiratory arrest neurological status. Hypothermia was initiated 120 min (median) after recovery of spontaneous circulation. Most patients (75 percent) required vasopressor support. During the first 3 days after cardiorespiratory arrest and therapeutic hypothermia, a progressive SOFA score decrease (median 11 on day 0, 10 on day 1 and 7 on day 2) was observed. DISCUSSION: In this study, therapeutic hypothermia was applied to all post-cardiorespiratory arrest patients and demonstrated good neurological outcome in surviving patients.

The neuroprotective role of therapeutic hypothermia after cardiac arrest. / Papel neuroprotector da hipotermia terapêutica pós paragem cardio-respiratória.

OBJECTIVES: Therapeutic hypothermia following cardiorespiratory arrest has been demonstrated to have cardio- and neuroprotective effects, resulting in improved survival and better neurological outcomes. The objective of this study was to assess the outcomes of patients undergoing therapeutic hypothermia following cardiorespiratory arrest. METHODS: A prospective, 10-month observational study of patients admitted to an intensive care unit and undergoing therapeutic hypothermia after cardiorespiratory arrest was undertaken. Therapeutic hypothermia was induced by cold fluid administration and body surface cooling in patients admitted no more than 12 hours after resuscitation from cardiorespiratory arrest. A target temperature of 33ºC was maintained for 24 hours. RESULTS: Overall, 12 patients were included (median age 64 years, 58% male). Half of the cardiorespiratory arrests were in-hospital. The median first-day Charlson Index, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II scores were of 2.9, 11 and 24.5, respectively. The intensive care unit mortality rate was 42% (N=5). Five of the 7 surviving patients recovered their pre-cardiorespiratory arrest neurological status. Hypothermia was initiated 120 min (median) after recovery of spontaneous circulation. Most patients (75%) required vasopressor support. During the first 3 days after cardiorespiratory arrest and therapeutic hypothermia, a progressive SOFA score decrease (median 11 on day 0, 10 on day 1 and 7 on day 2) was observed. DISCUSSION: In this study, therapeutic hypothermia was applied to all post-cardiorespiratory arrest patients and demonstrated good neurological outcome in surviving patients.

Anticuerpos IgM leptospirosicos en casos de hepatitis infecciosa aguda (HIA) en niños / IgM leptospira's antibodies in children with acute infectious hepatitis

Con el objetivo de conocer la frecuencia de asociación de infección aguda por Leptospiras y Hepatitis Infecciosa Aguda (HIA) en niños, se estudiaran 50 niños de ambos sexos, menores de 15 años, con evidencias de HIA (hiperbilirrubinemia bifásica y transaminasas elevadas), a los cuales se les determinó Ac-IgM-leptospirosica mediante el método de UREASA-ELISA encontrando 5 casos positivos (10 por ciento ), tres de los cuales también estuvieron asociados a la presencia de Ac. IgM. HAV, de aquí que solo en 2 casos (4 por ciento ) pudo encontrarse una relación entre infección aguda por Leptospira y HIA, concluyendo que aunque la infección leptospirósica es frecuente no lo es dentro del contexto de las HIA

Infección leptospirósica aguda de casos de hepatitis infectiocs aguda (HIA) en niños

Con el objetivo de conocer la frecuencia de asociacion de infección aguda por Leptospiras y Hepatitis Infecciosa Aguda (HIA) en niños, se estudiaron 50 niños de ambos sexos, menores de 15 años, con evidencias de HIA (Hiperbilirrubinemia bifásica y transaminass elevadas), a los cuales se les determinó AcIgM-leptospirósica mediante el método de UREASA ELISA encontrando 5 casos positivos (10%), tres de los cuales tambén estuvieron asociados a la presencia de AcIgm HAV, de aquí que solo en 2 casos (4%) pudo encontrarse una relación entre infección aguda por Lpetospiras y HIA, concluyendo que aunque la infección leptospirósica es frecuente así como su asociación a la enfermedad hepática, la enfermedad es infrecuente dentro del contexto de las hepatitis no A no B (4%)