Critically ill patients with COVID-19-associated acute kidney injury treated with kidney replacement therapy: Comparison between the first and second pandemic waves in São Paulo, Brazil.

INTRODUCTION: This study aimed to compare the characteristics and outcomes of critically ill patients with COVID-19-associated acute kidney injury (AKI) who were treated with kidney replacement therapy (KRT) in the first and second waves of the pandemic in the megalopolis of Sao Paulo, Brazil. METHODS: A multicenter retrospective study was conducted in 10 intensive care units (ICUs). Patients aged ≥18 years, and treated with KRT due to COVID-19-associated AKI were included. We compared demographic, laboratory and clinical data, KRT parameters and patient outcomes in the first and second COVID-19 waves. RESULTS: We assessed 656 patients (327 in the first wave and 329 in the second one). Second-wave patients were admitted later (7.1±5.0 vs. 5.6±3.9 days after the onset of symptoms, p<0.001), were younger (61.4±13.7 vs. 63.8±13.6 years, p = 0.023), had a lower frequency of diabetes (37.1% vs. 47.1%, p = 0.009) and obesity (29.5% vs. 40.0%, p = 0.007), had a greater need for vasopressors (93.3% vs. 84.6%, p<0.001) and mechanical ventilation (95.7% vs. 87.8%, p<0.001), and had higher lethality (84.8% vs. 72.7%, p<0.001) than first-wave patients. KRT quality markers were independently associated with a reduction in the OR for death in both pandemic waves. CONCLUSIONS: In the Sao Paulo megalopolis, the lethality of critically ill patients with COVID-19-associated AKI treated with KRT was higher in the second wave of the pandemic, despite these patients being younger and having fewer comorbidities. Potential factors related to this poor outcome were difficulties in health care access, lack of intra-hospital resources, delay vaccination and virus variants.

Acute respiratory distress syndrome following administration of gadolinium contrast agent: a case report.

BACKGROUND: Gadolinium-based contrast agents are used extensively in magnetic resonance imaging to assist diagnosis of medical conditions. Despite their documented safety profile, severe adverse events do occur, and their documentation may serve to raise the awareness of the medical community. CASE PRESENTATION: We report the case of a 15-year-old white Latin American female patient admitted to the intensive care unit for acute respiratory distress syndrome following administration of gadolinium. She did not have rash or tongue swelling but developed hypotension responsive to fluid administration and severe hypoxemia. Chest computed tomography revealed bilateral pulmonary compromise with multiple confluent consolidations. She received methylprednisolone and noninvasive ventilatory support including bilevel positive airway pressure ventilation and high-flow nasal cannula, and underwent a rapid recovery. CONCLUSION: Gadolinium-based contrast agent-induced acute respiratory distress syndrome, albeit rare, should be included in the differential diagnosis of respiratory failure shortly after magnetic resonance imaging, which is nowadays a frequent diagnostic procedure, potentially increasing the awareness of this serious complication.

An algorithm to predict the need for invasive mechanical ventilation in hospitalized COVID-19 patients: the experience in Sao Paulo.

BACKGROUND: We aimed to characterize patients hospitalized for coronavirus disease 2019 (COVID-19) and identify predictors of invasive mechanical ventilation (IMV). METHODS: We performed a retrospective cohort study in patients with COVID-19 admitted to a private network in Sao Paulo, Brazil from March to October 2020. Patients were compared in three subgroups: non-intensive care unit (ICU) admission (group A), ICU admission without receiving IMV (group B) and IMV requirement (group C). We developed logistic regression algorithm to identify predictors of IMV. RESULTS: We analyzed 1,650 patients, the median age was 53 years (42-65) and 986 patients (59.8%) were male. The median duration from symptom onset to hospital admission was 7 days (5-9) and the main comorbidities were hypertension (42.4%), diabetes (24.2%) and obesity (15.8%). We found differences among subgroups in laboratory values obtained at hospital admission. The predictors of IMV (odds ratio and 95% confidence interval [CI]) were male (1.81 [1.11-2.94], P=0.018), age (1.03 [1.02-1.05], P<0.001), obesity (2.56 [1.57-4.15], P<0.001), duration from symptom onset to admission (0.91 [0.85-0.98], P=0.011), arterial oxygen saturation (0.95 [0.92- 0.99], P=0.012), C-reactive protein (1.005 [1.002-1.008], P<0.001), neutrophil-to-lymphocyte ratio (1.046 [1.005-1.089], P=0.029) and lactate dehydrogenase (1.005 [1.003-1.007], P<0.001). The area under the curve values were 0.860 (95% CI, 0.829-0.892) in the development cohort and 0.801 (95% CI, 0.733-0.870) in the validation cohort. CONCLUSIONS: Patients had distinct clinical and laboratory parameters early in hospital admission. Our prediction model may enable focused care in patients at high risk of IMV.

Characteristics and Risk Factors for Mortality in Critically Ill Patients with COVID-19 Receiving Invasive Mechanical Ventilation: The Experience of a Private Network in Sao Paulo, Brazil.

Introduction: The use of invasive mechanical ventilation (IMV) in COVID-19 represents in an incremental burden to healthcare systems. Aim of the study: We aimed to characterize patients hospitalized for COVID-19 who received IMV and identify risk factors for mortality in this population. Material and Methods: A retrospective cohort study including consecutive adult patients admitted to a private network in Brazil who received IMV from March to October, 2020. A bidirectional stepwise logistic regression analysis was used to determine the risk factors for mortality. Results: We included 215 patients, of which 96 died and 119 were discharged from ICU. The mean age was 62.7 ± 15.4 years and the most important comorbidities were hypertension (62.8%), obesity (50.7%) and diabetes (40%). Non-survivors had lower body mass index (BMI) (28.3 [25.5; 31.6] vs. 31.2 [28.3; 35], p<0.001, and a shorter duration from symptom onset to intubation (8.5 [6.0; 12] days vs. 10 [8.0; 12.5] days, p = 0.005). Multivariable regression analysis showed that the risk factors for mortality were age (OR: 1.07, 95% CI: 1.03 to 1.1, p < 0.001), creatinine level at the intubation date (OR: 3.28, 95% CI: 1.47 to 7.33, p = 0.004), BMI (OR: 0.91, 95% CI: 0.84 to 0.99, p = 0.033), lowest PF ratio within 48 hours post-intubation (OR: 0.988, 95% CI: 0.979 to 0.997, p = 0.011), barotrauma (OR: 5.18, 95% CI: 1.14 to 23.65, p = 0.034) and duration from symptom onset to intubation (OR: 0.76, 95% CI: 0.76 to 0.95, p = 0.006). Conclusion: In our retrospective cohort we identified the main risk factors for mortality in COVID-19 patients receiving IMV: age, creatinine at the day of intubation, BMI, lowest PF ratio 48-hours post-intubation, barotrauma and duration from symptom onset to intubation.

Concurrent hospitalization of a married couple presenting with distinct symptoms but diagnosed with a life-threatening infectious disease.

We described the cases of a married couple hospitalized for distinct symptoms and developed a neuroparalytic syndrome with rapid progression. In Case 1, a 75-year-old woman was admitted for abdominal pain, diarrhea, and blurred vision. The patient developed acute respiratory failure, ptosis, and ophthalmoplegia. She died on day 15 because of an acute abdomen. In Case 2, her husband, a 71-year-old man, was admitted for diplopia. The patient developed abdominal distension and slurred speech. Later, he developed bilateral ptosis, ophthalmoparesis, and mydriasis. Botulism was suspected, and both patients received botulinum antitoxin. Our male patient survived but underwent prolonged rehabilitation.

COVID-19-associated acute kidney injury patients treated with renal replacement therapy in the intensive care unit: A multicenter study in São Paulo, Brazil.

INTRODUCTION: Multicenter studies involving patients with acute kidney injury (AKI) associated with the disease caused by the new coronavirus (COVID-19) and treated with renal replacement therapy (RRT) in developing countries are scarce. The objectives of this study were to evaluate the demographic profile, clinical picture, risk factors for mortality, and outcomes of critically ill patients with AKI requiring dialysis (AKI-RRT) and with COVID-19 in the megalopolis of São Paulo, Brazil. METHODS: This multicenter, retrospective, observational study was conducted in the intensive care units of 13 public and private hospitals in the metropolitan region of the municipality of São Paulo. Patients hospitalized in an intensive care unit, aged ≥ 18 years, and treated with RRT due to COVID-19-associated AKI were included. RESULTS: The study group consisted of 375 patients (age 64.1 years, 68.8% male). Most (62.1%) had two or more comorbidities: 68.8%, arterial hypertension; 45.3%, diabetes; 36.3%, anemia; 30.9%, obesity; 18.7%, chronic kidney disease; 15.7%, coronary artery disease; 10.4%, heart failure; and 8.5%, chronic obstructive pulmonary disease. Death occurred in 72.5% of the study population (272 patients). Among the 103 survivors, 22.3% (23 patients) were discharged on RRT. In a multiple regression analysis, the independent factors associated with death were the number of organ dysfunctions at admission and RRT efficiency. CONCLUSION: AKI-RRT associated with COVID-19 occurred in patients with an elevated burden of comorbidities and was associated with high mortality (72.5%). The number of organ dysfunctions during hospitalization and RRT efficiency were independent factors associated with mortality. A meaningful portion of survivors was discharged while dependent on RRT (22.3%).

COVID-19-associated acute kidney injury patients treated with renal replacement therapy in the intensive care unit: A multicenter study in São Paulo, Brazil

INTRODUCTION: Multicenter studies involving patients with acute kidney injury (AKI) associated with the disease caused by the new coronavirus (COVID-19) and treated with renal replacement therapy (RRT) in developing countries are scarce. The objectives of this study were to evaluate the demographic profile, clinical picture, risk factors for mortality, and outcomes of critically ill patients with AKI requiring dialysis (AKI-RRT) and with COVID-19 in the megalopolis of São Paulo, Brazil. METHODS: This multicenter, retrospective, observational study was conducted in the intensive care units of 13 public and private hospitals in the metropolitan region of the municipality of São Paulo. Patients hospitalized in an intensive care unit, aged ≥ 18 years, and treated with RRT due to COVID-19-associated AKI were included. RESULTS: The study group consisted of 375 patients (age 64.1 years, 68.8% male). Most (62.1%) had two or more comorbidities: 68.8%, arterial hypertension; 45.3%, diabetes; 36.3%, anemia; 30.9%, obesity; 18.7%, chronic kidney disease; 15.7%, coronary artery disease; 10.4%, heart failure; and 8.5%, chronic obstructive pulmonary disease. Death occurred in 72.5% of the study population (272 patients). Among the 103 survivors, 22.3% (23 patients) were discharged on RRT. In a multiple regression analysis, the independent factors associated with death were the number of organ dysfunctions at admission and RRT efficiency. CONCLUSION: AKI-RRT associated with COVID-19 occurred in patients with an elevated burden of comorbidities and was associated with high mortality (72.5%). The number of organ dysfunctions during hospitalization and RRT efficiency were independent factors associated with mortality. A meaningful portion of survivors was discharged while dependent on RRT (22.3%).

Concurrent hospitalization of a married couple presenting with distinct symptoms but diagnosed with a life-threatening infectious disease

ABSTRACT We described the cases of a married couple hospitalized for distinct symptoms and developed a neuroparalytic syndrome with rapid progression. In Case 1, a 75-year-old woman was admitted for abdominal pain, diarrhea, and blurred vision. The patient developed acute respiratory failure, ptosis, and ophthalmoplegia. She died on day 15 because of an acute abdomen. In Case 2, her husband, a 71-year-old man, was admitted for diplopia. The patient developed abdominal distension and slurred speech. Later, he developed bilateral ptosis, ophthalmoparesis, and mydriasis. Botulism was suspected, and both patients received botulinum antitoxin. Our male patient survived but underwent prolonged rehabilitation.

Characterization of Antibiotic Use, Documented Infection and Prevalence of Multidrug-Resistant Organisms in Palliative Care Patients Admitted to a Private Hospital in Brazil: A Retrospective, Cohort Study.

OBJECTIVES: Antibiotic use in palliative care patients is a frequent dilemma. The benefits of their use in terms of quality of end-of-life care or survival improvement are not clear and the potential harm and futility of this practice not well established. Our aim was to characterise the prevalence of antibiotic use, documented infection and multidrug-resistant organisms (MDROs) colonisation among palliative care patients admitted to a private hospital in Brazil. MATERIALS AND METHODS: Retrospective analysis of all palliative care patients admitted to our hospital during 1 year, including demographic characteristics, diagnosis of infectious disease at admission, antibiotic use during hospital stay, infectious agents isolated in cultures, documented MDRO colonisation and hospital mortality. RESULTS: A total of 114 patients were included in the analysis. Forty-five (39%) were male and the median age was 83 years. About 78% of the patients had an infectious diagnosis at hospital admission and 80% of the patients not admitted with an infectious diagnosis used antibiotics during their stay, out of which a great proportion of large spectrum antibiotics. Previous MDRO colonisation and hospital mortality were similar between patients admitted with or without an infectious diagnosis. CONCLUSION: Infection is the leading cause of hospital admission in palliative care patients. However, antibiotics prescription is also very prevalent during hospital stay of patients not admitted with an infectious condition. Mortality is very high regardless of the initial reason for hospital admission. Therefore, the impact of multiple large spectrum antibiotics prescription and consequent significant cost burden should be urgently confronted with the real benefit to these patients.

Urine biochemistry assessment in critically ill patients: controversies and future perspectives.

In the past, urine biochemistry was a major tool in acute kidney injury (AKI) management. Classic papers published some decades ago established the values of the urine indices which were thought to distinguish "pre-renal" (functional) AKI attributed to low renal perfusion and "renal" (structural) AKI attributed to acute tubular necrosis (ATN). However, there were a lot of drawbacks and limitations in these studies and some recent articles have questioned the utility of measuring urine electrolytes especially because they do not seem to adequately inform about renal perfusion nor AKI duration (transient vs. persistent). At the same time, the "pre-renal" paradigm has been consistently criticized because hypoperfusion followed by ischemia and ATN does not seem to explain most of the AKI developing in critically ill patients and distinct AKI durations do not seem to be clearly related to different pathophysiological mechanisms or histopathological findings. In this new context, other possible roles for urine biochemistry have emerged. Some studies have suggested standardized changes in the urine electrolyte composition preceding increases in serum creatinine independently of AKI subsequent duration, which might actually be due to intra-renal microcirculatory changes and activation of sodium-retaining mechanisms even in the absence of impaired global renal blood flow. In the present review, the points of controversy regarding urine biochemistry assessment were evaluated as well as future perspectives for its role in AKI monitoring. An alternative approach for the interpretation of measured urine electrolytes is proposed which needs further larger studies to be validated and incorporated in daily ICU practice.

Back to Basics: Is There a Good Reason to Not Systematically Measure Urine Creatinine in Acute Kidney Injury Monitoring?

Regardless of the recent advancements in the understanding of the pathophysiology of acute kidney injury (AKI), its diagnosis remains fundamentally dependent on the serum creatinine (sCr) level and urine output (UO), both of which are considered late markers of AKI, offering only a vague idea of the actual creatinine clearance (CrCl). Although not ideal, CrCl is still the most common alternative of the glomerular filtration rate (GFR) in clinical practice. It is generally accepted that early diagnosis of AKI must reveal kidney impairment before sCr increases. Much effort has been made to find tubular and glomerular markers of injury which increase (in blood and/or in urine) before the 'official' diagnosis of AKI. Most of these markers are expensive and not widely available, especially in developing countries. Urine creatinine (CrU), the major link between sCr and UO, has been systematically ignored and clinicians are usually unaware of its value. The reasons for this are unclear, but it may be related to the lack of a reference range, dependence of its concentration value on the urine flow (which in turn is only adequately assessed with an indwelling urinary catheter) and the clinical unavailability of its counterbalance part - creatinine production. Changes in urine tend to precede changes in blood in the course of AKI development and recovery. Hence, it is important to bear in mind that changes in sCr signal renal dysfunction with a significant delay. The search for a more dynamic, 'real-time' but pragmatic assessment of renal function, especially in patients at risk of abrupt decrease in GFR is certainly one of the most relevant focus of research in the field of AKI monitoring. Systematic CrU assessment may be highly relevant in this case.

Metabolic acid-base adaptation triggered by acute persistent hypercapnia in mechanically ventilated patients with acute respiratory distress syndrome.

OBJECTIVE: Hypercapnia resulting from protective ventilation in acute respiratory distress syndrome triggers metabolic pH compensation, which is not entirely characterized. We aimed to describe this metabolic compensation. METHODS: The data were retrieved from a prospective collected database. Variables from patients' admission and from hypercapnia installation until the third day after installation were gathered. Forty-one patients with acute respiratory distress syndrome were analyzed, including twenty-six with persistent hypercapnia (PaCO2 > 50mmHg > 24 hours) and 15 non-hypercapnic (control group). An acid-base quantitative physicochemical approach was used for the analysis. RESULTS: The mean ages in the hypercapnic and control groups were 48 ± 18 years and 44 ± 14 years, respectively. After the induction of hypercapnia, pH markedly decreased and gradually improved in the ensuing 72 hours, consistent with increases in the standard base excess. The metabolic acid-base adaptation occurred because of decreases in the serum lactate and strong ion gap and increases in the inorganic apparent strong ion difference. Furthermore, the elevation in the inorganic apparent strong ion difference occurred due to slight increases in serum sodium, magnesium, potassium and calcium. Serum chloride did not decrease for up to 72 hours after the initiation of hypercapnia. CONCLUSION: In this explanatory study, the results indicate that metabolic acid-base adaptation, which is triggered by acute persistent hypercapnia in patients with acute respiratory distress syndrome, is complex. Furthermore, further rapid increases in the standard base excess of hypercapnic patients involve decreases in serum lactate and unmeasured anions and increases in the inorganic apparent strong ion difference by means of slight increases in serum sodium, magnesium, calcium, and potassium. Serum chloride is not reduced.

Simple blood and urinary parameters measured at ICU admission may sign for AKI development in the early postoperative period: a retrospective, exploratory study.

Recent studies have suggested that some blood physicochemical and urinary biochemical parameters have a standardized behavior during acute kidney injury (AKI) development. The changes in these parameters frequently begin to occur before significant rises in serum creatinine (sCr) and may help in identifying patients with more subtle decreases in glomerular filtration rate (GFR). Surgical patients have an increased risk of AKI but renal impairment is usually not evident at ICU admission. We hypothesized that the surgical patients who have AKI diagnosed in the early postoperative period have an impaired GFR since ICU admission, indirectly inferred by alterations in these blood physicochemical and urinary biochemical parameters even in the presence of a still normal sCr. We retrospectively evaluated 112 surgical patients who were categorized according to AKI development during the first 3 ICU days. Twenty-eight patients developed AKI, most of them in the first day (D1) after ICU admission (D0). AKI patients had, at D0, lower serum pH and albumin, higher C - reactive protein (CRP), lower urine sodium (NaU) and fractional excretion of urea (FEUr). Fractional excretion of potassium (FEK) was high in both groups at D0 but remained high in the subsequent days only in AKI patients. Very low CRP and high serum albumin, high NaU and FEUr values at ICU admission had a significant negative predictive value for AKI. We concluded that some easily assessed parameters in blood and urine may help to identify patients with indirect signs of increased inflammatory response and decreased GFR at ICU admission, which could help to predict the risk of postoperative AKI development.

Adaptação metabólica diante de hipercapnia persistente aguda em pacientes submetidos à ventilação mecânica por síndrome do desconforto respiratório agudo / Metabolic acid-base adaptation triggered by acute persistent hypercapnia in mechanically ventilated patients with acute respiratory distress syndrome

RESUMO Objetivo: A hipercapnia resultante da ventilação protetora na síndrome do desconforto respiratório agudo desencadeia uma compensação metabólica do pH que ainda não foi completamente caracterizada. Nosso objetivo foi descrever esta compensação metabólica. Métodos: Os dados foram recuperados a partir de uma base de dados registrada de forma prospectiva. Foram obtidas as variáveis dos pacientes no momento da admissão e quando da instalação da hipercapnia até o terceiro dia após sua instalação. Analisamos 41 pacientes com síndrome do desconforto respiratório agudo, incluindo 26 com hipercapnia persistente (pressão parcial de gás carbônico acima de 50mmHg por mais de 24 horas) e 15 sem hipercapnia (Grupo Controle). Para a realização da análise, utilizamos uma abordagem físico-química quantitativa do metabolismo acidobásico. Resultados: As médias de idade dos Grupos com Hipercapnia e Controle foram, respectivamente, de 48 ± 18 anos e 44 ± 14 anos. Após a indução da hipercapnia, o pH diminuiu acentuadamente e melhorou gradualmente nas 72 horas seguintes, de forma coerente com os aumentos observados no excesso de base padrão. A adaptação metabólica acidobásica ocorreu em razão de diminuições do lactato sérico e do strong ion gap e de aumentos na diferença aparente de strong ions inorgânicos. Além do mais, a elevação da diferença aparente de strong ions inorgânicos ocorreu por conta de ligeiros aumentos séricos de sódio, magnésio, potássio e cálcio. O cloreto sérico não diminuiu por até 72 horas após o início da hipercapnia. Conclusão: A adaptação metabólica acidobásica, que é desencadeada pela hipercapnia aguda persistente em pacientes com síndrome do desconforto respiratório agudo, foi complexa. Mais ainda, aumentos mais rápidos no excesso de base padrão em pacientes com hipercapnia envolveram diminuições séricas de lactato e íons não medidos, e aumentos na diferença aparente de strong ions inorgânicos, por meio de ligeiros aumentos séricos de sódio, magnésio, cálcio e potássio. Não ocorreu redução do cloreto sérico.

ABSTRACT Objective: Hypercapnia resulting from protective ventilation in acute respiratory distress syndrome triggers metabolic pH compensation, which is not entirely characterized. We aimed to describe this metabolic compensation. Methods: The data were retrieved from a prospective collected database. Variables from patients' admission and from hypercapnia installation until the third day after installation were gathered. Forty-one patients with acute respiratory distress syndrome were analyzed, including twenty-six with persistent hypercapnia (PaCO2 > 50mmHg > 24 hours) and 15 non-hypercapnic (control group). An acid-base quantitative physicochemical approach was used for the analysis. Results: The mean ages in the hypercapnic and control groups were 48 ± 18 years and 44 ± 14 years, respectively. After the induction of hypercapnia, pH markedly decreased and gradually improved in the ensuing 72 hours, consistent with increases in the standard base excess. The metabolic acid-base adaptation occurred because of decreases in the serum lactate and strong ion gap and increases in the inorganic apparent strong ion difference. Furthermore, the elevation in the inorganic apparent strong ion difference occurred due to slight increases in serum sodium, magnesium, potassium and calcium. Serum chloride did not decrease for up to 72 hours after the initiation of hypercapnia. Conclusion: In this explanatory study, the results indicate that metabolic acid-base adaptation, which is triggered by acute persistent hypercapnia in patients with acute respiratory distress syndrome, is complex. Furthermore, further rapid increases in the standard base excess of hypercapnic patients involve decreases in serum lactate and unmeasured anions and increases in the inorganic apparent strong ion difference by means of slight increases in serum sodium, magnesium, calcium, and potassium. Serum chloride is not reduced.

Kinetics of arterial carbon dioxide during veno-venous extracorporeal membrane oxygenation support in an apnoeic porcine model.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a technique widely used worldwide to improve gas exchange. Changes in ECMO settings affect both oxygen and carbon dioxide. The impact on oxygenation can be followed closely by continuous pulse oximeter. Conversely, carbon dioxide equilibrates much slower and is not usually monitored directly. METHODS: We investigated the time to stabilization of arterial carbon dioxide partial pressure (PaCO2) following step changes in ECMO settings in 5 apnoeic porcine models under veno-venous ECMO support with polymethylpentene membranes. We collected sequential arterial blood gases at a pre-specified interval of 50 min using a sequence of standardized blood and sweep gas flow combinations. RESULTS: Following the changes in ECMO parameters, the kinetics of carbon dioxide was dependent on sweep gas and ECMO blood flow. With a blood flow of 1500 mL/min, PaCO2 takes longer than 50 min to equilibrate following the changes in sweep gas flow. Furthermore, the sweep gas flow from 3.0 to 10.0 L/min did not significantly affect PaCO2. However, with a blood flow of 3500 mL/min, 50 min was enough for PaCO2 to reach the equilibrium and every increment of sweep gas flow (up to 10.0 L/min) resulted in additional reductions of PaCO2. CONCLUSIONS: Fifty minutes was enough to reach the equilibrium of PaCO2 after ECMO initiation or after changes in blood and sweep gas flow with an ECMO blood flow of 3500 ml/min. Longer periods may be necessary with lower ECMO blood flows.