Efficacy of ultrasound-guided percutaneous transhepatic biliary drainage for acute obstructive suppurative cholangitis combined with septic shock.

OBJECTIVES: This study aimed to investigate the efficacy of ultrasound-guided Percutaneous Transhepatic Biliary Drainage (PTCD) for the treatment of Acute Obstructive Suppurative Cholangitis (AOSC) combined with septic shock due to choledocholithiasis, and its effect on inflammatory factors. METHODS: Clinical data of 86 patients with AOSC and septic shock admitted to our hospital between January 2019 and May 2021 were retrospectively analyzed and grouped according to different treatment methods. Among them, 43 patients who underwent Endoscopic Retrograde Cholangiopancreatography (ERCP) and Endoscopic Nasobiliary Drainage (ENBD) were included in the Control Group (CNG), and 43 patients who underwent ultrasound-guided PTCD were included in the Study Group (SG). RESULTS: The total effective rate in the SG (88.37%) was higher than that in the CNG (69.77%) (p < 0.05); after surgery, the serum inflammatory factors PCT, IL-6, TNF-α, CRP levels, liver function indicators such as TBIL, DBIL, AST, ALT levels, and stress response indicators including NPY, PGE2, 5-HT levels were reduced, and were lower in the SG than in the CNG (p < 0.05); postoperatively, CD3+, CD4+, and CD4+/CD8+ levels in the CNG were significantly lower than those before surgery (p < 0.05); Postoperatively, CD3+, CD4+, and CD4+/CD8+ levels in the SG were significantly higher than those in the CNG (p < 0.05); and the complication rate in the SG (6.98%) was lower than that in the CNG (25.58%) (p < 0.05). CONCLUSIONS: Ultrasound-guided PTCD for AOSC combined with septic shock can facilitate the recovery of liver and immune functions with a low complication rate.

[Lower socioeconomic conditions are associated with higher rates but similar outcomes in Sepsis in children]. / Condiciones socioeconómicas más bajas se asocian con tasas de sepsis infantil más altas pero con resultados similares.

Sepsis is an important cause of pediatric morbidity and mortality, especially in low-income countries. Data on regional prevalence, mortality trends, and their relationship with socioeconomic variables are scarce. OBJECTIVE: to determine the regional prevalence, mortality, and sociodemographic situation of patients diagnosed with severe sepsis (SS) and septic shock (SSh) admitted to Pediatric Intensive Care Units (PICUs). PATIENTS AND METHOD: patients aged 1 to 216 months admitted to 47 participating PICUs with a diagnosis of SS or SSh between January 1, 2010, and December 31, 2018, were included. Secondary analysis was performed on the Argentine Society of Intensive Care Benchmarking Quality Program (SATI-Q) database for SS and SSh and a review of the annual reports of the Argentine Ministry of Health and the National Institute of Statistics and Census for the sociodemographic indices of the respective years. RESULTS: 45,480 admissions were recorded in 47 PICUs, 3,777 of them with a diagnosis of SS and SSh. The combined prevalence of SS and SSh decreased from 9.9% in 2010 to 6.6% in 2018. The combined mortality decreased from 34.5% to 23.5%. Multivariate analysis showed that the Odds ratio (OR) of the association between SS and SSh mortality was 1.88 (95% CI: 1.46-2.32) and 2.4 (95% CI: 2.16-2.66), respectively, adjusted for malignant disease, PIM2, and mechanical ventilation. The prevalence of SS and SSh in different health regions (HR) was associated with the percentage of poverty and infant mortality rate (p < 0.001). However, there was no association between sepsis mortality and HR adjusted for PIM2. CONCLUSIONS: Prevalence and mortality of SS and SSh have decreased over time in the participating PICUs. Lower socioeconomic conditions were associated with higher prevalence but similar sepsis outcomes.

Effect of Present at Time of Surgery on Unadjusted and Risk-Adjusted Postoperative Complication Rate.

BACKGROUND: Present at the time of surgery (PATOS) is an important measure to collect in postoperative complication surveillance systems because it may affect a patient's risk of a subsequent complication and the estimation of postoperative complication rates attributed to the healthcare system. The American College of Surgeons (ACS) NSQIP started collecting PATOS data for 8 postoperative complications in 2011, but no one has used these data to quantify how this may affect unadjusted and risk-adjusted postoperative complication rates. STUDY DESIGN: This study was a retrospective observational study of the ACS NSQIP database from 2012 to 2018. PATOS data were analyzed for the 8 postoperative complications of superficial, deep, and organ space surgical site infection; pneumonia; urinary tract infection; ventilator dependence; sepsis; and septic shock. Unadjusted postoperative complication rates were compared ignoring PATOS vs taking PATOS into account. Observed to expected ratios over time were also compared by calculating expected values using multiple logistic regression analyses with complication as the dependent variable and the 28 nonlaboratory preoperative variables in the ACS NSQIP database as the independent variables. RESULTS: In 5,777,108 patients, observed event rates for each outcome were reduced by between 6.1% (superficial surgical site infection) and 52.5% (sepsis) when PATOS was taken into account. The observed to expected ratios were similar each year for all outcomes, except for sepsis and septic shock in the early years. CONCLUSIONS: Taking PATOS into account is important for reporting unadjusted event rates. The effect varied by type of complication-lowest for superficial surgical site infection and highest for sepsis and septic shock. Taking PATOS into account was less important for risk-adjusted outcomes (observed to expected ratios), except for sepsis and septic shock.

Acute gastrointestinal failure is associated with worse hemodynamic and perfusion parameters over 48 h after admission in patients with septic shock: Retrospective cohort study.

BACKGROUND: This study aimed to investigate the relationship between acute gastrointestinal injury (AGI) and hemodynamic and perfusion parameters in the first week of intensive care unit (ICU) admission and evaluate the association of AGI with ICU and hospital outcomes in patients with septic shock undergoing mechanical ventilation. METHODS: This retrospective cohort study applied the criteria proposed by the European Society of Intensive Medicine to classify the participants into risk/dysfunction group (AGI grade I and II) and failure group (AGI grade III and IV). Hemodynamic and perfusion parameters data previously collected in the first 48 h after ICU admission (admission, 12, 24, 48 h) were analyzed. RESULTS: A total of 163 were included and classified into AGI grades I (n = 79), II (n = 64), III (n = 20), and IV (none). Groups consisted of AGI risk/dysfunction (n = 143, 87.8%) and AGI failure (n = 20, 12.2%) patients. Patients with AGI failure had higher heart rate and mottling score (MS) at admission, lower mean arterial pressure, and an oliguria incidence at 12 h compared with those without AGI failure. Skin MS and abdominal primary site of infection were risk factors for AGI failure. AGI failure tended to be a risk factor for ICU mortality (risk ratio [95% CI]: 1.37 [0.99-1.89]; P = 0.053). CONCLUSION: AGI was frequently observed in patients with septic shock in the first week of ICU admission. Higher heart rate and MS and lower mean arterial pressure and incidence of oliguria were identified in patients with AGI failure compared with those without. AGI failure was associated with ICU mortality.

Síndrome inflamatorio multisistémico asociado a COVID-19: a propósito de un caso clínico con fenotipo shock e íleo paralítico / Multisystem inflammatory syndrome associated with COVID-19: clinical case with shock phenotype and paralytic ileus / Síndrome inflamatória multissistêmica associada à COVID-19: relato de caso com fenótipo de choque e íleo paralítico

La enfermedad por coronavirus 2019 (COVID-19) causada por la infección por SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) se ha extendido por todo el mundo desde diciembre de 2019. Luego de la primera ola de COVID-19, se reporta por primera vez en mayo de 2020 en el Reino Unido un estado hiperinflamatorio asociado temporalmente a la infección por SARS-CoV-2 en un grupo de niños ingresados a unidades de cuidado intensivo pediátrico. Este nuevo fenotipo, con características similares a la enfermedad de Kawasaki y al síndrome del shock tóxico, se ha denominado síndrome inflamatorio multisistémico en niños (MIS-C). Es fundamental la sospecha y el reconocimiento tempranos de esta entidad, con el fin de ofrecer un tratamiento médico oportuno, para prevenir la muerte y el desarrollo de secuelas. Presentamos el caso de una preescolar de 5 años, en la que se realizó diagnóstico de MIS-C con un fenotipo shock e íleo paralítico.

The coronavirus disease 2019 (COVID-19) caused by the infection by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has spread worldwide since December 2019. After the first wave of COVID-19, a hyperinflammatory condition temporarily associated with SARS-CoV-2 infection appeared in a group of children admitted to pediatric intensive care units and reported for the first time in May 2020 in the United Kingdom. This new phenotype shared characteristics with the Kawasaki disease and toxic shock syndrome and has been called multisystem inflammatory syndrome in children (MIS-C). Early suspicion and recognition of this condition is key in order to offer timely medical treatment to prevent death and the development of sequelae. We present the case of a 5-year-old child, in which diagnosis of MIS-C with a shock phenotype and paralytic ileus.

A doença de coronavírus 2019 (COVID-19) causada pela infecção por SARS-CoV-2 (síndrome respiratória aguda grave coronavírus 2) se espalhou pelo mundo desde dezembro de 2019. Após a primeira onda de COVID-19, houve relatos pela primeira vez em maio de 2020 no Reino Unido duma doença hiperinflamatória temporariamente associada à infecção por SARS-CoV-2 num grupo de crianças internadas em unidades de terapia intensiva pediátrica. Esse novo fenótipo com características semelhantes à doença de Kawasaki e a síndrome do choque tóxico foi chamado de síndrome inflamatória multissistêmica em crianças (MIS-C). A suspeita precoce e o reconhecimento dessa entidade são essenciais, a fim de oferecer tratamento médico oportuno, para prevenir a morte e o desenvolvimento de sequelas. Apresentamos o caso de uma menina pré-escolar de 5 anos que foi diagnosticada com MIS-C com fenótipo de choque e íleo paralítico.

Frequency and burden of neurological manifestations upon hospital presentation in COVID-19 patients: Findings from a large Brazilian cohort.

BACKGROUND: Scientific data regarding the prevalence of COVID-19 neurological manifestations and prognosis in Latin America countries is still lacking. Therefore, the study aims to understand neurological manifestations of SARS-CoV 2 infection and outcomes in the Brazilian population. METHODS: This study is part of the Brazilian COVID-19 Registry, a multicentric cohort, including data from 37 hospitals. For the present analysis, patients were grouped according to the presence of reported symptoms (i.e., headache; anosmia and ageusia; syncope and dizziness) vs. clinically-diagnosed neurological manifestations (clinically-defined neurological syndrome: neurological signs or diagnoses captured by clinical evaluation) and matched with patients without neurological manifestations by age, sex, number of comorbidities, hospital of admission, and whether or not patients had underlying neurological disease. RESULTS: From 6,635 hospitalized patients with COVID-19, 30.8% presented reported neurological manifestations, 10.3% were diagnosed with a neurological syndrome and 60.1% did not show any neurological manifestations. In patients with reported symptoms, the most common ones were headache (20.7%), ageusia (11.1%) and anosmia (8.0%). In patients with neurological syndromes, acute encephalopathy was the most common diagnosis (9.7%). In the matched analysis, patients with neurological syndromes presented more cases of septic shock (17.0 vs. 13.0%, p = 0.045), intensive care unit admission (45.3 vs. 38.9%, p = 0.023), and mortality (38.7 vs. 32.6%, p = 0.026; and 39.2 vs. 30.3%, p < 0.001) when compared to controls. CONCLUSION: COVID-19 in-hospital patients with clinically defined neurological syndromes presented a higher incidence of septic shock, ICU admission and death when compared to controls.

[Management of refractory septic shock with blood purification therapy using a special filter. Report of one case]. / COVID-19, shock séptico refractario y terapia extracorpórea de purificación sanguínea con OXIRIS®.

Sepsis is one of the leading causes of death in critically ill patients with COVID-19 and blood purification therapies have a role to immunomodulate the excessive inflammatory response and improve clinical results. One of the devices designed for these therapies is the oXiris® filter, allowing to perform renal replacement therapy combined with selective adsorption of endotoxins and cytokines. We report a 55-year-old male with COVID who developed a septic shock secondary to a sepsis caused by Pseudomona aeruginosa, refractory to the usual management. A veno-venous continuous hemofiltration was started using the oXiris® filter for 48 hours. Subsequently, there was an improvement in clinical perfusion parameters and a reduction in inflammatory markers. The patient was discharged from the intensive care one month later.

[Extreme electrolyte depletion associated with septic shock as a form of presentation of cystic fibrosis]. / Depleción electrolítica extrema asociada con shock séptico como forma de presentación de fibrosis quística.

In the pediatric emergency department, dehydrated children are one of the most frequent causes for consultation, however, the coexistence of hyponatremia with hypochloremia and metabolic alkalosis is rare. The presence of metabolic alkalosis due to chloride depletion has been reported as a form of presentation of Cystic Fibrosis (CF). OBJECTIVE: to describe a case of cystic fibrosis of unusual presen tation in a pediatric patient. CLINICAL CASE: we report a 3-month-old previously healthy male infant who presented with internal environment abnormalities consisting of metabolic alkalosis, hypona tremia, hypokalemia, and extreme hypochloremia associated with septic shock due to mixed viral- bacterial pneumonia (Rhino/enterovirus, Streptococcus pneumoniae, and Staphylococcus aureus). Cys tic fibrosis (CF) was suspected, thus the diagnosis was corroborated by sweat test and genetic study which showed the pathogenic variants c.2834C>T (p.Ser945Leu) and c.3484C>T (p.Arg1162X), both heterozygous. CONCLUSION: special attention should be paid to the existence of hypochloremia with metabolic alkalosis and hyponatremia associated or not with pulmonary disease, suspecting CF as the first option. This consideration becomes more relevant in those countries where the neonatal screening test is not widely available.

Health Resource Use in Survivors of Pediatric Septic Shock in the United States.

OBJECTIVES: To evaluate postdischarge health resource use in pediatric survivors of septic shock and determine patient and hospitalization factors associated with health resource use. DESIGN: Secondary analyses of a multicenter prospective observational cohort study. SETTING: Twelve academic PICUs. PATIENTS: Children greater than or equal to 1 month and less than 18 years old hospitalized for community-acquired septic shock who survived to 1 year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For 308/338 patients (91%) with baseline and greater than or equal to one postdischarge survey, we evaluated readmission, emergency department (ED) visits, new medication class, and new device class use during the year after sepsis. Using negative binomial regression with bidirectional stepwise selection, we identified factors associated with each outcome. Median age was 7 years (interquartile range, 2-13), 157 (51%) had a chronic condition, and nearly all patients had insurance (private [n = 135; 44%] or government [n = 157; 51%]). During the year after sepsis, 128 patients (42%) were readmitted, 145 (47%) had an ED visit, 156 (51%) started a new medication class, and 102 (33%) instituted a new device class. Having a complex chronic condition was independently associated with readmission and ED visit. Documented infection and higher sum of Pediatric Logistic Organ Dysfunction--2 hematologic score were associated with readmission, whereas younger age and having a noncomplex chronic condition were associated with ED visit. Factors associated with new medication class use were private insurance, neurologic insult, and longer PICU stays. Factors associated with new device class use were preadmission chemotherapy or radiotherapy, presepsis Functional Status Scale score, and ventilation duration greater than or equal to 10 days. Of patients who had a new medication or device class, most had a readmission (56% and 61%) or ED visit (62% and 67%). CONCLUSIONS: Children with septic shock represent a high-risk cohort with high-resource needs after discharge. Interventions and targeted outcomes to mitigate postdischarge resource use may differ based on patients' preexisting conditions.

Methylene blue for the treatment of refractory septic shock secondary to listeriosis in a paediatric patient.

Current therapies frequently used for refractory septic shock include hydrocortisone, vasopressin, extracorporeal membrane oxygenation (ECMO) support, inodilators, levosimendan and methylene blue. The evidence for these treatments is very limited. We present a case of a 5-year-old patient with refractory septic shock, secondary to Listeria monocytogenes meningitis. She presented with status epilepticus and developed septic shock. Shock persisted despite multiple high-dose vasoactive medications. ECMO support was not available. The medical team decided to use methylene blue to revert the vasoplegia, with excellent results. Shortly after the administration, vasopressors were weaned off and the high lactate cleared. She developed severe neurological sequelae due to brain haemorrhage secondary to the Listeria meningitis. The evidence supporting methylene blue for refractory septic shock in paediatric patients is limited. This case represents the effectiveness of this therapy without secondary effects.

Effects of physical therapy with neuromuscular electrical stimulation in acute and late septic shock patients: A randomised crossover clinical trial.

BACKGROUND: Patients with sepsis and immobility in the intensive care unit are associated with muscle weakness, and early mobilisation can counteract it. However, during septic shock, mobilisation is often delayed due to the severity of the illness. Neuromuscular electrical stimulation (NMES) may be an alternative to mobilise these patients early. This study aims to identify whether NMES performed within the first 72 hours of septic shock diagnosis or later is safe from a metabolic perspective. METHODS: This is the analysis of two randomised controlled crossover studies. Patients with acute septic shock (within the first 72 hours of diagnosis) and sepsis and septic shock in the late phase (after 72 hours of diagnosis) were eligible. Patients were submitted in a random order to the intervention protocol (dorsal decubitus position with the lower limbs raised and NMES) and control (dorsal decubitus position with the lower limbs raised without NMES). The patients were allocated in group 1 (intervention and control) or group 2 (control and intervention) with a wash-out period of 4 to 6 hours. Metabolic variables were evaluated by indirect calorimetry. RESULTS: Sixteen patients were analysed in the acute septic shock study and 21 in the late sepsis/septic shock study. There were no significant differences between Oxygen Consumption (VO2) values in the acute phase of septic shock when the baseline period, intervention, and control protocols were compared (186.59 ± 46.10; 183.64 ± 41.39; 188.97 ± 44.88, p>0.05- expressed in mL/Kg/min). The same was observed when the VO2 values in the late phase were compared (224.22 ± 53.09; 226.20 ± 49.64; 226.79 ± 58.25, p>0.05). The other metabolic variables followed the same pattern, with no significant differences between the protocols. When metabolic variables were compared between acute to late phase, significant differences were observed (p<0.05). CONCLUSIONS: As metabolic rates in septic shock patients had no increase during NMES, either in the first 72 hours of diagnosis or later, NMES can be considered safe from a metabolic viewpoint, even despite the higher metabolic demand in the acute phase of shock. TRIAL REGISTRATION: NCT03193164; NCT03815994. Registered on June 5, 2017; November 13, 2018 (clinicaltrials.gov/).

COVID-19, shock séptico refractario y terapia extracorpórea de purificación sanguínea con OXIRIS® / Management of refractory septic shock with blood purification therapy using a special filter: report of one case

Sepsis is one of the leading causes of death in critically ill patients with COVID-19 and blood purification therapies have a role to immunomodulate the excessive inflammatory response and improve clinical results. One of the devices designed for these therapies is the oXiris® filter, allowing to perform renal replacement therapy combined with selective adsorption of endotoxins and cytokines. We report a 55-year-old male with COVID who developed a septic shock secondary to a sepsis caused by Pseudomona aeruginosa, refractory to the usual management. A veno-venous continuous hemofiltration was started using the oXiris® filter for 48 hours. Subsequently, there was an improvement in clinical perfusion parameters and a reduction in inflammatory markers. The patient was discharged from the intensive care one month later.

Association Between Hyperlactatemia, Perfusional Parameters, and Lymphocyte Mitochondrial Dysfunction in Septic Shock Patients.

INTRODUCTION: In septic shock, mitochondrial dysfunction, and hypoperfusion are the main triggers of multi-organ failure. Little is known about the crosstalk between mitochondrial dysfunction and hemodynamic alterations, especially in the post-resuscitation phase. Here, we assess whether hypoperfusion and lactate levels are associated with oxygen consumption linked to mitochondrial bioenergetic activity in lymphocytes of patients admitted with septic shock. PATIENTS AND METHODS: Prospective cohort study in patients with septic shock defined as the requirement of vasopressors to maintain a mean arterial pressure 65 mm Hg after initial fluid administration. Basal mitochondrial and Complex I respiration was measured to evaluate mitochondrial activity. Both variables and capillary refill time were compared with arterial lactate post-fluid resuscitation. We also compared mitochondrial activity measurements between patients with and without hypoperfusion status. RESULTS: A total of 90 patients were included in analysis. The median arterial lactate at the time of septic shock diagnosis was 2.0 mmol/Dl (IQR 1.3-3.0). Baseline respiration at the time of septic shock diagnosis was correlated with lactate (Spearman -0.388, 95% CI -0.4893 to -0.1021; P = 0.003), as well as Complex I respiration (Spearman -0.403, 95% CI -0.567 to -0.208; P < 0.001). Patients with hypoperfusion status had no difference in basal respiration when compared with patients who did not have hypoperfusion status (P = 0.22) nor in Complex I respiration (P = 0.09). CONCLUSION: Changes in lymphocytic mitochondrial metabolism are associated with post-resuscitation arterial lactate in septic shock; however, they are not associated with the presence of a hypoperfusional status. In this scenario, it is therefore suggested that systemic perfusion and mitochondrial metabolism have different courses.

Calcificación miocárdica de etiología multifactorial / Myocardial calcification with multifactorial etiology

En el presente trabajo se describe un caso de muerte súbita en una mujer de 70 años que fallece 20 días después de ser dada de alta tras ingreso por infección urinaria secundaria a litiasis renal complicada con shock séptico e insuficiencia renal y respiratoria. En el corazón se identificó una cardiopatía isquémica crónica y extensas áreas de miocardio calcificado. Además, se exponen los tipos de calcificaciones del miocardio existentes y sus causas; y se analizan aquellos factores que en el caso presentado han podido causar la calcificación del miocardio(AU)

In the present report, we describe a case of sudden death in a 70-year-old woman who died 20 days after been discharged after admission for urinary infection secondary to renal lithiasis complicated with septic shock and renal and respiratory failure. It has been identified chronic ischemic heart disease and extensive areas of calcified myocardium. Also, we review myocardial calfications subtypes and its causes, and we analyze the specifics of the presented case(AU)

Efetividade da infusão estendida de Piperacilina-tazobactana - Meropenem no tratamento de pacientes sépticos adultos queimados através da modelagem farmacocinética farmacodinâmica, PK/P / Meropenem and piperacillin/tazobactam by extended infusion and PK/PD approach for drug effectiveness

Introdução: Meropenem (MER) e Piperacilina/Tazobactana (PTZ) são agentes antimicrobianos largamente prescritos para pacientes grandes queimados internados em Unidade de Terapia Intensiva (UTI) com infecções nosocomiais causadas por Gram-negativos sensíveis CIM 2 mg/L, Enterobacteriaceae, EB e Non-enterobacteriaceae, NEB. A síndrome da resposta inflamatória sistêmica (SRIS) que ocorre durante o choque séptico no grande queimado pode causar alteração na farmacocinética do paciente em terapia intensiva, de modo que a dose recomendada pode não atingir o alvo desejado contra Gram-negativos de sensibilidade intermediária CIM >2 mg/L. Objetivo: Investigar a efetividade dos beta-lactâmicos piperacilina e meropenem na infusão estendida comparada à infusão intermitente recomendada, para os pacientes sépticos grandes queimados através da abordagem farmacocinética-farmacodinâmica (PK/PD). Ética, casuística e procedimentos: Autor e co-autores declararam não haver conflito de interesse. O protocolo foi aprovado, registro CAAE 07525118.3.0000.0068. No presente protocolo de estudo investigaram-se 36 pacientes sépticos grandes queimados, ambos os gêneros (12F/24M) em terapia intensiva do choque séptico com piperacilina-tazobactana 4,5g q6h ou meropenem 1g q8h. Os pacientes incluídos foram estratificados em dois grupos com base na administração através da infusão intermitente, 0,5 h (G1) ou da infusão estendida, 3 h (G2), ambos com 16 pacientes cada. Duas amostras sanguíneas (1,5mL/cada) foram coletadas no estado de equilíbrio (Steady State), 3ª e 5ª hora do início da infusão. Os níveis séricos de PTZ e MER foram mensurados através de cromatografia líquida, e a farmacocinética (PK) dos dois grupos de pacientes foi comparada aos dados reportados em voluntários sadios. A abordagem PK/PD foi aplicada para avaliação da cobertura do antimicrobiano a partir da estimativa do índice de predição de efetividade (% fΔT>CIM) e da probabilidade de alcançar o alvo terapêutico (PTA) com base no alvo PK/PD recomendado, 100%fΔT>CIM. Resultados e discussão: As características de admissão dos pacientes G1/G2 foram expressas através de mediana e interquartil: Clcr 115 (90-148) / 127 (90-170) ml/min; 30 (24-31) / 27 (24- 33,5) anos, 70 (61-75) / 71 (65-75) kg, 30 (20-42) / 33,9 (18-38,4)% área total de superfície queimada, SAPS3 53 (45-57) / 48 (37,8-59,5). Na admissão dos pacientes na UTI registrou-se G1/G2: trauma térmico (17/16), trauma elétrico (1/2), lesão inalatória (11/11), ventilação mecânica (16/9) e vasopressores foram necessários em 15/8 pacientes, G1/G2. Ocorreram diferentes alterações na farmacocinética dos dois beta-lactâmicos após a infusão estendida versus a infusão intermitente quando comparadas com dados relatados em voluntários sadios. Evidenciou-se prolongamento da meia vida decorrente do aumento do volume de distribuição. Estes resultados impactaram diferentemente a cobertura. O monitoramento de biomarcadores inflamatórios expressos em medianas (G1/G2) evidenciou aumento do PCR: 232/183mg/L e leucocitose (leucócitos 11/14 mil cel/mm3, neutrófilos 9/10 mil cel/mm3) na fase precoce do choque séptico. Relativamente à microbiologia dos isolados, a erradicação dos patógenos ocorreu para todos os pacientes após a infusão estendida contra Gram-negativos sensíveis (CIM: 2 mg/L), e de sensibilidade intermediária (CIM 4mg/L) como a K. pneumoniae e P. aeruginosa, enquanto a infusão intermitente garantiu erradicação de patógenos apenas até CIM 2 mg/L. Conclusão: Evidenciou-se a superioridade da infusão estendida frente à infusão intermitente na cobertura dos dois antimicrobianos, no alvo terapêutico considerado 100%fΔT>CIM. Registraram-se alterações na farmacocinética destes agentes nos pacientes frente aos dados reportados para voluntários sadios. Diferença significativa entre grupos (G1/G2) foi encontrada com relação meia vida biológica, e ao volume de distribuição tanto pata a piperacilina quanto para o meropenem

Background: Meropenem (MER) and Piperacillin/Tazobactam (PTZ), antimicrobial betalactam agents are widely prescribed to burn patients from the Intensive Care Unit (ICU) with nosocomial infections caused by Gram-negative strains. Change in the pharmacokinetics of critically ill patient occurs during the systemic inflammatory response syndrome (SIRS) at the course of septic shock. Then, the recommended dose administered by intermittent infusion, 0.5 hr cannot reach the target against gram-negative strains MIC > 2 mg/L. Subject: To investigate drug effectiveness of the beta-lactams piperacilin and meropenem in extended infusion compared to the recommended intermittent infusion in critically ill septic burn patients using pharmacokinetic-pharmacodynamic (PK/PD) approach. Ethics, Casuistry and Methods: All authors declared there is no conflict of interests. Ethical approval CAAE, register 07525118.3.0000.0068. It was investigated in the study protocol 36 septic burn patients of both genders (12M / 24F), undergoing antimicrobial therapy with PTZ 4.5 g q6h or MER 1g q8h. Based on the chosen antimicrobial therapy and drug infusion prescribed by the physician, patients were stratified in groups with intermittent 0.5h infusion (G1) or with the extended 3h infusion (G2), both groups with 16 patients each. Two blood samples were collected at the steady state (1.5mL / each), at the 3rd and 5th hrs of starting the infusion. Serum levels were measured by liquid chromatography. Pharmacokinetics (PK) of MER or PTZ was compared to data reported in healthy volunteers for both groups of patients. PK/PD approach was applied to estimate the drug effectiveness index (fΔT> MIC) and to assess the probability of target attained (PTA) based on the recommended PK/PD target, 100% fΔT> MIC. Results and discussion: Characteristics of patients admission G1/G2 were: Clcr 115(90- 148)/127(90-170) ml/min; 30(24-31)/27(24-34) yrs, 70(61-75)/71(65-75) kg, 30(20- 42)/33.9(18-38.4)% total burn surface area, SAPS3 53(45-57)/48(37.8-59.5), medians (interquartile): thermal trauma occurred (17/16), electric trauma (1/2), inhalation injury (11/11), mechanical ventilation (9/16) and vasopressors required in 15/8 patients. It was demonstrated that different PK changes occurred for both beta-lactam agents after the extended or intermittent infusion by comparison with data reported in healthy volunteers. PK changes were related to the prolongation of biological half-life and increases on volume of distribution with impact on pharmacodynamics. On the other hand, meropenem total body clearance reduced by 50% at the earlier period of septic shock could be explained by the reduction of MER-transporters expression in the tubular renal secretion, once only patients with renal function preserved were included in the study protocol. Inflammatory biomarkers increased at the earlier period of septic shock: C-rp 232/183mg/L; leukocytes 11/14*103cel/mm3, neutrophils 9/10*103cel/mm3, medians, G1/G2. Clinical and microbiological cure was obtained for all patients of G1 against MIC < 2mg/L after intermittent 0.5 h infusion; while PK/PD target was attained for G2 patients undergoing antimicrobial therapy with MER or PTZ by extended infusion against gram negative strains K. pneumoniae, P. aeruginosa up to MIC 4mg L. Conclusion: Superiority of the extended infusion over intermitent infusion was obtained for the two antimicrobials was evidenced, in the therapeutic target considered 100%fΔT>CIM. Changes in the pharmacokinetics of these agents were recorded in patients compared to data reported for healthy volunteers. A significant difference between groups (G1/G2) was found in relation to biological half-life and volume of distribution for both piperacillin and meropenem

Prevalence and factors associated with sepsis and septic shock in oncological patients in intensive therapy.

OBJECTIVES: to analyze factors associated with sepsis and septic shock in cancer patients in the Intensive Care Unit. METHODS: cross-sectional, retrospective study with a quantitative approach, with a sample of 239 patients in an oncology hospital. Secondary data from medical records were used. The outcome variable was "presence of sepsis and/or septic shock"; and exposures: sex, length of stay, origin, use of invasive procedures and primary tumor site. Descriptive, bivariate analyzes and multiple logistic regression models were performed. RESULTS: the prevalence of sepsis was 95% CI: 14.7-24.7 and septic shock of 95% CI: 37.7-50.3. In the multiple analysis, sepsis and/or septic shock were associated with hospital stay longer than seven days, being from the Emergency Department, presence of invasive procedures and hematological site. CONCLUSIONS: sepsis and/or septic shock in cancer patients were associated with clinical characteristics and health care factors.

Abordagem Farmacocinética -Farmacodinâmica (PK/PD) Em Pacientes Sépticos Grandes Queimados: Avaliação do Meropenem Em Adultos Jovens Após 1g Q8h, Infusão Estendida / Pharmacokinetic -Pharmacodynamic Approach (PK/PD) In Septic Burn Young Adult Patients: Meropenem 1g q8h, extended infusion

Introdução: O Meropenem é um carbapenêmico de amplo espectro, prescrito na terapia do choque séptico nos pacientes graves adultos de UTI, com infecções graves causadas por patógenos Gram-negativos susceptíveis. Objetivo: Avaliar a efetividade do Meropenem em pacientes sépticos queimados, investigar a farmacocinética na fase precoce e na fase tardia durante o curso do choque séptico e o impacto no desfecho clínico. Ética, Casuística e Procedimentos: Aprovação ética, registro CAAE07525118.3.0000.0068; nenhum conflito de interesse declarado foi obtido dos autores. Após assinatura do TCLE pelo responsável legal, o paciente foi incluído no protocolo. Investigou-se a população de 15 pacientes sépticos grandes queimados, adultos de ambos os gêneros (10 M/ 5F) com função renal preservada (Clcr> 50 ml/min). As características demográficas da população de pacientes incluídos foram idade de 37(33 -41) anos, 71(59,5 - 80,0) kg e índice de massa corpórea de 24,3(20,6-24,7) kg/m2, medianas (interquartil). Registrou-se o escore SAPS*3 54(47-59) de admissão dos pacientes na UTI; a superfície corpórea total queimada foi de 33% (18,3-34,4), SCTQ medianas (interquartil). A lesão inalatória e o uso de vasopressores foram registrados em 12/15 pacientes após trauma térmico/ elétrico (10/5). Após intubação orotraqueal, a ventilação mecânica foi registrada em 13/15 pacientes. A terapia empírica do choque séptico com Meropenem no regime de 1g q8h, por infusão estendida de 3 horas, foi iniciada após a coleta das culturas. Realizou-se coleta seriada de amostras sanguíneas para dosagem sérica do antimicrobiano por cromatografia líquida. Aplicou-se o modelo aberto monocompartimental para estudo da farmacocinética e estimativa dos parâmetros, meia vida biológica, depuração total corporal e volume de distribuição. A abordagem farmacocinética-farmacodinâmica (PK-PD) foi baseada na dosagem sérica do Meropenem e na taxa de eliminação, para estimativa do índice de predição de efetividade (% ƒ Δ?T> CIM), considerando o novo alvo terapêutico de 100% ƒ Δ?T> CIM. Utilizou-se estatística não paramétrica pela aplicação do teste de Wilcoxon para dados pareados e testes de correlação linear. Resultados e Discussão: Registrou-se alteração dos parâmetros farmacocinéticos nos pacientes sépticos investigados frente aos dados reportados para voluntários sadios. Evidenciou-se redução na taxa de eliminação e da depuração total corporal; o prolongamento da meia vida biológica ocorreu pelo aumento do volume de distribuição. Estas alterações impactaram estendendo a cobertura do Meropenem, na fase precoce do choque séptico, contra os patógenos de susceptibilidade intermediária com CIM 4 mg/L. Conclusão: A cobertura do Meropenem foi garantida contra os patógenos isolados até CIM 2 mg/L para todos os pacientes. Adicionalmente, ocorreu a erradicação de patógenos de susceptibilidade intermediária CIM 4 mg/L, pela cobertura que foi atingida apenas na fase precoce do choque séptico. Então, a abordagem PK / PD contribui para a obtenção do resultado

Background: Meropenem is a carbapenêmic, agent largely prescribed to septic patients in the Intensive Care Units with severe infections caused by Gram-negative susceptible strains. Objective: To evaluate Meropenem effectiveness in ICU septic burn patients and to investigate pharmacokinetic changes that could impact the desired outcome by eradication of Gram-negative strains of intermediate susceptibility. Ethics, Casuistry and Methods: Ethical approval register CAEE 07525118.3.0000.0068was obtained; no conflicts of interest to declare were obtained from all authors. Fifteen burn adult patients of both genders (10 M/ 5F) with preserved renal function (Clcr> 50 ml/min) were investigated after TCLE signed. Demographic characteristics of patients included were: 37(33 -41) years, 71(59.5- 80.0) kg, 24.3 (20.6-24.7) kg/m2 body mass index, medians (quartiles). ICU patients admission was based on SAPS*3 score of 54(47-59), 33% (18.3-34.4) TBSA medians (quartiles). Inhalation injury and vasopressors requirements were in 12/15 patients after fire/electricity (10/5, proportion). Mechanical ventilation was necessary in 13/15 patients. Antimicrobial therapy of septic shock with meropenem 1g q8h 3 hours infusion started, after cultures collection. A serial of blood samples was collected from the central catheter after a minimum of 48 hours of Meropenem therapy for drug serum measurements by liquid chromatography. One compartment open model was applied to estimate PK data related to the elimination rate constant, biological half-life, total body clearance and volume of distribution PK/PD approach was based on serum trough levels and elimination rate constant to estimate the predictive index of drug effectiveness (% fΔT>CIM), based on the new PK/PD target 100% fΔT>CIM. Non parametric statistics was applied, Wilcoxon test for paired data and linear correlations. Results: Pharmacokinetic changes occurred in septic burn patients investigated by comparison with results reported in healthy volunteers as follows by the reduction on elimination rate constant and also on total body clearance, in spite of preserved renal function for all patients included. In addition, a prolongation of biological half-life occurred as a consequence of increases on volume of distribution. Pharmacodynamics was impacted by PK changes only at the earlier period of septic shock, once pathogens isolated of intermediate susceptibility up to MIC 4 mg/L were eradicated. Conclusion: Meropenem effectiveness was guaranteed against Gram-negative up to MIC 2 mg/L strains isolated for all patients. In addition, eradication of pathogens of intermediate susceptibility MIC 4 mg/L strains occurred only at the earlier period of septic shock. Then, PK/PD approach contributes to desired outcome achievement

Case report of a child with influenza and fatal community-associated methicillin-resistant Staphylococcus aureus sepsis.

In the present study, we report the incidence of septic shock syndrome associated with methicillin-resistant Staphylococcus aureus in a child who initially presented influenza-like illness and developed septic shock shortly after 48 h of hospitalization, and eventually died within a few hours of the onset of sepsis. S. aureus isolated from the blood culture was characterized as the community-associated strain carrying the staphylococcal cassette chromosome mec (SCCmec) type IV element. Therefore, it is important to better understand the community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections and their potential association with influenza for early diagnosis and successful treatment of this fatal disease.

Fluid overload in patients with septic shock and lactate clearance as a therapeutic goal: a retrospective cohort study. / Sobrecarga de fluidos em pacientes com choque séptico e depuração de lactato como alvo terapêutico: um estudo de coorte retrospectiva.

OBJECTIVE: To assess whether fluid overload in fluid therapy is a prognostic factor for patients with septic shock when adjusted for lactate clearance goals. METHODS: This was a retrospective cohort study conducted at a level IV care hospital in Bogotá, Colombia. A cohort of patients with septic shock was assembled. Their characteristics and fluid balance were documented. The patients were stratified by exposure levels according to the magnitude of fluid overload by body weight after 24 hours of therapy. Mortality was determined at 30 days, and an unconditional logistic regression model was created, adjusting for confounders. The statistical significance was established at p ≤ 0.05. RESULTS: There were 213 patients with septic shock, and 60.8% had a lactate clearance ≥ 50% after treatment. Ninety-seven (46%) patients developed fluid overload ≥ 5%, and only 30 (13%) developed overload ≥ 10%. Patients exhibiting fluid overload ≥ 5% received an average of 6227mL of crystalloids (SD ± 5838mL) in 24 hours, compared to 3978mL (SD ± 3728mL) among unexposed patients (p = 0.000). The patients who developed fluid overload were treated with mechanical ventilation (70.7% versus 50.8%) (p = 0.003), albumin (74.7% versus 55.2%) (p = 0.003) and corticosteroids (53.5% versus 35.0%) (p = 0.006) more frequently than those who did not develop fluid overload. In the multivariable analysis, cumulative fluid balance was not associated with mortality (OR 1.03; 95%CI 0.89 - 1.20). CONCLUSIONS: Adjusting for the severity of the condition and adequate lactate clearance, cumulative fluid balance was not associated with increased mortality in this Latin American cohort of septic patients.