Assessment of risk factors for in-hospital mortality after intensive care unit discharge.

CONTEXT: Post-intensive care unit (ICU) mortality predictors are unknown. OBJECTIVE: To assess post-ICU in-hospital mortality predictors. MATERIALS AND METHODS: Analysis of 296 patients discharged alive from a medical-surgical ICU during an 18-month period. RESULTS: Post-ICU in-hospital mortality was 22.6%. Nonsurvivors had significantly higher Charlson comorbidity score and more often had a tracheostomy. C-reactive protein (CRP) "alert measurement", ≥ 6 mg/dL, independently discriminated survivors from nonsurvivors. DISCUSSION: A CRP "alert measurement" or the need for tracheostomy may be used to identify patients with high risk of dying after ICU discharge. CONCLUSIONS: Charlson comorbidity score, CRP and tracheostomy predicted post-ICU in-hospital mortality.

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.

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.

What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care. / O que mudou entre os períodos de pico e de platô durante a primeira onda do SARS-CoV-2? Estudo multicêntrico português em unidades de cuidados intensivos.

OBJECTIVE: To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. METHODS: This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. RESULTS: Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39; p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136; p = 0.6), antibiotic therapy (57% versus 64%; p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%; p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5]; p = 0.002) and presented a higher use of vasopressors (47% versus 36%; p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%; p < 0.001) at admission, prone positioning (45% versus 36%; p = 0.04), and hydroxychloroquine (59% versus 10%; p < 0.001) and lopinavir/ritonavir (41% versus 10%; p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%; p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. CONCLUSION: There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave.

OBJETIVO: Analisar e comparar as características de pacientes críticos com a COVID-19, a abordagem clínica e os resultados entre os períodos de pico e de platô na primeira onda pandêmica em Portugal. MÉTODOS: Este foi um estudo de coorte multicêntrico ambispectivo, que incluiu pacientes consecutivos com a forma grave da COVID-19 entre março e agosto de 2020 de 16 unidades de terapia intensiva portuguesas. Definiram-se as semanas 10 - 16 e 17 - 34 como os períodos de pico e platô. RESULTADOS: Incluíram-se 541 pacientes adultos com mediana de idade de 65 [57 - 74] anos, a maioria do sexo masculino (71,2%). Não houve diferenças significativas na mediana de idade (p = 0,3), no Simplified Acute Physiology Score II (40 versus 39; p = 0,8), na pressão parcial de oxigênio/fração inspirada de oxigênio (139 versus 136; p = 0,6), na terapia com antibióticos na admissão (57% versus 64%; p = 0,2) ou na mortalidade aos 28 dias (24,4% versus 22,8%; p = 0,7) entre o período de pico e platô. Durante o período de pico, os pacientes tiveram menos comorbidades (1 [0 - 3] versus 2 [0 - 5]; p = 0,002); fizeram mais uso de vasopressores (47% versus 36%; p < 0,001) e ventilação mecânica invasiva na admissão (58,1% versus 49,2%; p < 0,001), e tiveram mais prescrição de hidroxicloroquina (59% versus 10%; p < 0,001), lopinavir/ritonavir (41% versus 10%; p < 0,001) e posição prona (45% versus 36%; p = 0,04). Entretanto, durante o platô, observou-se maior uso de cânulas nasais de alto fluxo (5% versus 16%; p < 0,001) na admissão, remdesivir (0,3% versus 15%; p < 0,001) e corticosteroides (29% versus 52%; p < 0,001), além de menor tempo de internação na unidade de terapia intensiva (12 versus 8 dias; p < 0,001). CONCLUSÃO: Houve mudanças significativas nas comorbidades dos pacientes, nos tratamentos da unidade de terapia intensiva e no tempo de internação entre os períodos de pico e platô na primeira onda da COVID-19.

suPAR in the assessment of post intensive care unit prognosis: a pilot study. / suPAR na avaliação do prognóstico após permanência na unidade de terapia intensiva: um estudo piloto.

OBJECTIVE: To determine the performance of soluble urokinase-type plasminogen activator receptor upon intensive care unit discharge to predict post intensive care unit mortality. METHODS: A prospective observational cohort study was conducted during a 24-month period in an 8-bed polyvalent intensive care unit. APACHE II, SOFA, C-reactive protein, white cell count and soluble urokinase-type plasminogen activator receptor on the day of intensive care unit discharge were collected from patients who survived intensive care unit admission. RESULTS: Two hundred and two patients were included in this study, 29 patients (18.6%) of whom died after intensive care unit discharge. Nonsurvivors were older and more seriously ill upon intensive care unit admission with higher severity scores, and nonsurvivors required extended use of vasopressors than did survivors. The area under the receiver operating characteristics curves of SOFA, APACHE II, C-reactive protein, white cell count, and soluble urokinase-type plasminogen activator receptor at intensive care unit discharge as prognostic markers of hospital death were 0.78 (95%CI 0.70 - 0.86); 0.70 (95%CI 0.61 - 0.79); 0.54 (95%CI 0.42 - 0.65); 0.48 (95%CI 0.36 - 0.58); and 0.68 (95%CI 0.58 - 0.78), respectively. SOFA was independently associated with a higher risk of in-hospital mortality (OR 1.673; 95%CI 1.252 - 2.234), 28-day mortality (OR 1.861; 95%CI 1.856 - 2.555) and 90-day mortality (OR 1.584; 95%CI 1.241 - 2.022). CONCLUSION: At intensive care unit discharge, soluble urokinase-type plasminogen activator receptor is a poor predictor of post intensive care unit prognosis.

OBJETIVO: Determinar o desempenho da dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel quando da alta da unidade de terapia intensiva para predição da mortalidade após permanência na mesma unidade. MÉTODOS: Durante 24 meses conduziu-se um estudo prospectivo observacional de coorte em uma unidade de terapia intensiva polivalente de oito leitos. Colheram-se os seguintes dados: APACHE II, SOFA, níveis de proteína C-reativa e receptor ativador de plasminogênio tipo uroquinase solúvel, além de contagem de leucócitos no dia da alta da unidade de terapia intensiva, em pacientes que sobreviveram à permanência na unidade de terapia intensiva. RESULTADOS: Durante este período, incluíram-se no estudo 202 pacientes; 29 (18,6%) morreram após alta da unidade de terapia intensiva. Os não sobreviventes eram mais idosos e tinham enfermidades mais graves quando admitidos à unidade de terapia intensiva, com escores de severidade mais elevados, e necessitaram de vasopressores por mais tempo do que os que sobreviveram. As áreas sob a curva Característica de Operação do Receptor para SOFA, APACHE II, proteína C-reativa, contagem de leucócitos e receptor ativador de plasminogênio tipo uroquinase solúvel, no momento da alta da unidade de terapia intensiva, avaliadas como marcadores de prognóstico de morte hospitalar, foram, respectivamente, 0,78 (IC95% 0,70 - 0,86); 0,70 (IC95% 0,61 - 0,79); 0,54 (IC95% 0,42 - 0,65); 0,48 (IC95% 0,36 - 0,58); 0,68 (IC95% 0,58 - 0,78). O SOFA associou-se de forma independente com risco mais elevado de morte no hospital (OR 1,673; IC95% 1,252 - 2,234), assim como para mortalidade após 28 dias (OR 1,861; IC95% 1,856 - 2,555) e mortalidade após 90 dias (OR 1,584; IC95% 1,241 - 2,022). CONCLUSÃO: A dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel na alta unidade de terapia intensiva teve um valor prognóstico fraco de mortalidade após a permanência nesta unidade.

O que mudou entre os períodos de pico e de platô durante a primeira onda do SARS-CoV-2? Estudo multicêntrico português em unidades de cuidados intensivos / What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care

RESUMO Objetivo: Analisar e comparar as características de pacientes críticos com a COVID-19, a abordagem clínica e os resultados entre os períodos de pico e de platô na primeira onda pandêmica em Portugal. Métodos: Este foi um estudo de coorte multicêntrico ambispectivo, que incluiu pacientes consecutivos com a forma grave da COVID-19 entre março e agosto de 2020 de 16 unidades de terapia intensiva portuguesas. Definiram-se as semanas 10 - 16 e 17 - 34 como os períodos de pico e platô. Resultados: Incluíram-se 541 pacientes adultos com mediana de idade de 65 [57 - 74] anos, a maioria do sexo masculino (71,2%). Não houve diferenças significativas na mediana de idade (p = 0,3), no Simplified Acute Physiology Score II (40 versus 39; p = 0,8), na pressão parcial de oxigênio/fração inspirada de oxigênio (139 versus 136; p = 0,6), na terapia com antibióticos na admissão (57% versus 64%; p = 0,2) ou na mortalidade aos 28 dias (24,4% versus 22,8%; p = 0,7) entre o período de pico e platô. Durante o período de pico, os pacientes tiveram menos comorbidades (1 [0 - 3] versus 2 [0 - 5]; p = 0,002); fizeram mais uso de vasopressores (47% versus 36%; p < 0,001) e ventilação mecânica invasiva na admissão (58,1% versus 49,2%; p < 0,001), e tiveram mais prescrição de hidroxicloroquina (59% versus 10%; p < 0,001), lopinavir/ritonavir (41% versus 10%; p < 0,001) e posição prona (45% versus 36%; p = 0,04). Entretanto, durante o platô, observou-se maior uso de cânulas nasais de alto fluxo (5% versus 16%; p < 0,001) na admissão, remdesivir (0,3% versus 15%; p < 0,001) e corticosteroides (29% versus 52%; p < 0,001), além de menor tempo de internação na unidade de terapia intensiva (12 versus 8 dias; p < 0,001). Conclusão: Houve mudanças significativas nas comorbidades dos pacientes, nos tratamentos da unidade de terapia intensiva e no tempo de internação entre os períodos de pico e platô na primeira onda da COVID-19.

ABSTRACT Objective: To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. Methods: This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. Results: Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39; p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136; p = 0.6), antibiotic therapy (57% versus 64%; p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%; p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5]; p = 0.002) and presented a higher use of vasopressors (47% versus 36%; p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%; p < 0.001) at admission, prone positioning (45% versus 36%; p = 0.04), and hydroxychloroquine (59% versus 10%; p < 0.001) and lopinavir/ritonavir (41% versus 10%; p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%; p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. Conclusion: There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave.

Severe diltiazem poisoning treated with hyperinsulinaemia-euglycaemia and lipid emulsion.

Introduction. Calcium channel blockers (CCBs) drugs are widely used in the treatment of cardiovascular diseases. CCB poisoning is associated with significant cardiovascular toxicity and is potentially fatal. Currently, there is no specific antidote and the treatment of CCB poisoning is supportive; however, this supportive therapy is often insufficient. We present a clinical case of severe diltiazem poisoning and the therapeutic approaches that were used. Case Report. A 55-year-old male was admitted to the intensive care unit (ICU) after voluntary multiple drug intake, including extended release diltiazem (7200 mg). The patient developed symptoms of refractory shock to conventional therapy and required mechanical ventilation, a temporary pacemaker, and renal replacement therapy. Approximately 17 hours after drug intake, hyperinsulinaemia-euglycaemia with lipid emulsion therapy was initiated, followed by progressive haemodynamic recovery within approximately 30 minutes. The toxicological serum analysis 12 h after drug ingestion revealed a diltiazem serum level of 4778 ng/mL (therapeutic level: 40-200 ng/mL). Conclusions. This case report supports the therapeutic efficacy of hyperinsulinaemia-euglycaemia and lipid emulsion in the treatment of severe diltiazem poisoning.

suPAR na avaliação do prognóstico após permanência na unidade de terapia intensiva: um estudo piloto / suPAR in the assessment of post intensive care unit prognosis: a pilot study

RESUMO Objetivo: Determinar o desempenho da dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel quando da alta da unidade de terapia intensiva para predição da mortalidade após permanência na mesma unidade. Métodos: Durante 24 meses conduziu-se um estudo prospectivo observacional de coorte em uma unidade de terapia intensiva polivalente de oito leitos. Colheram-se os seguintes dados: APACHE II, SOFA, níveis de proteína C-reativa e receptor ativador de plasminogênio tipo uroquinase solúvel, além de contagem de leucócitos no dia da alta da unidade de terapia intensiva, em pacientes que sobreviveram à permanência na unidade de terapia intensiva. Resultados: Durante este período, incluíram-se no estudo 202 pacientes; 29 (18,6%) morreram após alta da unidade de terapia intensiva. Os não sobreviventes eram mais idosos e tinham enfermidades mais graves quando admitidos à unidade de terapia intensiva, com escores de severidade mais elevados, e necessitaram de vasopressores por mais tempo do que os que sobreviveram. As áreas sob a curva Característica de Operação do Receptor para SOFA, APACHE II, proteína C-reativa, contagem de leucócitos e receptor ativador de plasminogênio tipo uroquinase solúvel, no momento da alta da unidade de terapia intensiva, avaliadas como marcadores de prognóstico de morte hospitalar, foram, respectivamente, 0,78 (IC95% 0,70 - 0,86); 0,70 (IC95% 0,61 - 0,79); 0,54 (IC95% 0,42 - 0,65); 0,48 (IC95% 0,36 - 0,58); 0,68 (IC95% 0,58 - 0,78). O SOFA associou-se de forma independente com risco mais elevado de morte no hospital (OR 1,673; IC95% 1,252 - 2,234), assim como para mortalidade após 28 dias (OR 1,861; IC95% 1,856 - 2,555) e mortalidade após 90 dias (OR 1,584; IC95% 1,241 - 2,022). Conclusão: A dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel na alta unidade de terapia intensiva teve um valor prognóstico fraco de mortalidade após a permanência nesta unidade.

ABSTRACT Objective: To determine the performance of soluble urokinase-type plasminogen activator receptor upon intensive care unit discharge to predict post intensive care unit mortality. Methods: A prospective observational cohort study was conducted during a 24-month period in an 8-bed polyvalent intensive care unit. APACHE II, SOFA, C-reactive protein, white cell count and soluble urokinase-type plasminogen activator receptor on the day of intensive care unit discharge were collected from patients who survived intensive care unit admission. Results: Two hundred and two patients were included in this study, 29 patients (18.6%) of whom died after intensive care unit discharge. Nonsurvivors were older and more seriously ill upon intensive care unit admission with higher severity scores, and nonsurvivors required extended use of vasopressors than did survivors. The area under the receiver operating characteristics curves of SOFA, APACHE II, C-reactive protein, white cell count, and soluble urokinase-type plasminogen activator receptor at intensive care unit discharge as prognostic markers of hospital death were 0.78 (95%CI 0.70 - 0.86); 0.70 (95%CI 0.61 - 0.79); 0.54 (95%CI 0.42 - 0.65); 0.48 (95%CI 0.36 - 0.58); and 0.68 (95%CI 0.58 - 0.78), respectively. SOFA was independently associated with a higher risk of in-hospital mortality (OR 1.673; 95%CI 1.252 - 2.234), 28-day mortality (OR 1.861; 95%CI 1.856 - 2.555) and 90-day mortality (OR 1.584; 95%CI 1.241 - 2.022). Conclusion: At intensive care unit discharge, soluble urokinase-type plasminogen activator receptor is a poor predictor of post intensive care unit prognosis.

[Severe imported malaria in critical care patients]. / Malária grave importada em doentes críticos.

INTRODUCTION: Imported malaria is a frequent diagnosis in Portugal, and in the most severe clinical forms it may present a high mortality rate. MATERIAL AND METHODS: We present seven cases of severe imported malaria, admitted to an intensive care unit between 2000 and 2010, with particular focus on risk factors, clinical presentation, treatment and results. RESULTS: All patients had a history of recent travel to African endemic areas for malaria. Plasmodium falciparum was the agent isolated in all cases. Most patients had an inadequate prophylaxis. High parasitaemia in non-immune patients and treatment delay were associated with more severe clinical presentation. All the cases were complicated by organ failure, and three patients needed organ support and in two exchange blood transfusions were performed. There was one single death that was associated with marked delay in the initiation of therapy. CONCLUSION: In these patients, early and aggressive treatment, with a organ support in a critical care setting, allowed a good outcome with low mortality and no significant sequelae, despite the severity of presentation.

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.

Metformin-induced lactic acidosis: a case series.

INTRODUCTION: Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin. CASE PRESENTATION: We present two case reports of metformin-associated lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin (3 g/day), perindopril and acetylsalicylic acid. She was admitted to the emergency department two weeks later with abdominal pain and psychomotor agitation. Physical examination revealed only signs of poor perfusion. Laboratory evaluation revealed hyperkalemia, elevated creatinine and blood urea nitrogen and mild leukocytosis. Arterial blood gases showed severe lactic acidemia. She was admitted to the intensive care unit. Vasopressor and ventilatory support was initiated and continuous venovenous hemodiafiltration was instituted. Twenty-four hours later, full clinical recovery was observed, with return to a normal serum lactate level. The patient was discharged from the intensive care unit on the sixth day. The second patient is a 69 year old male with a past medical history of hypertension, type 2 diabetes mellitus and ischemic heart disease who was on metformin (4 g/day), glycazide, acetylsalicylic acid and isosorbide dinitrate. He was admitted to the emergency department in shock with extreme bradycardia. Initial evaluation revealed severe lactic acidosis and elevated creatinine and urea. The patient was admitted to the Intensive Care Unit and commenced on continuous venovenous hemodiafiltration in addition to other supportive measures. A progressive recovery was observed and he was discharged from the intensive care unit on the seventh day. CONCLUSION: We present two case reports of severe lactic acidosis most probably associated with high doses of metformin in patients with no known contraindications for metformin prescription. In both patients no other condition was identified to cause such severe lactic acidosis. Although controversial, lactic acidosis should be considered in patients taking metformin.

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.