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1.
Proc Natl Acad Sci U S A ; 118(10)2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33658363

RESUMO

Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed binding, implying the presence of natural inhibitor(s) preventing binding at normal pH. Testing micromolar concentrations of divalent cations showed that zinc supported the robust binding of sialylated glycoproteins with HMGB1. Further characterizing HMGB1 as a sialic acid-binding lectin, we found that optimal binding takes place at normal blood pH and is markedly reduced when pH is adjusted with lactic acid to levels found in sepsis. Glycan array studies confirmed the binding of HMGB1 to sialylated glycan sequences typically found on plasma glycoproteins, with binding again being dependent on zinc and normal blood pH. Thus, HMGB1-mediated hyperactivation of innate immunity in sepsis requires acidosis, and micromolar zinc concentrations are protective. We suggest that the potent inflammatory effects of HMGB1 are kept in check via sequestration by plasma sialoglycoproteins at physiological pH and triggered when pH and zinc levels fall in late stages of sepsis. Current clinical trials independently studying zinc supplementation, HMGB1 inhibition, or pH normalization may be more successful if these approaches are combined and perhaps supplemented by infusions of heavily sialylated molecules.


Assuntos
Acidose/sangue , Proteína HMGB1/sangue , Sepse/sangue , Sialoglicoproteínas/sangue , Zinco/sangue , Acidose/imunologia , Acidose/metabolismo , Acidose/patologia , Proteínas de Transporte , Proteína HMGB1/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Imunidade Inata , Lipopolissacarídeos/farmacologia , Polissacarídeos/química , Sepse/imunologia , Sepse/patologia , Ácidos Siálicos/química , Sialoglicoproteínas/química , Zinco/metabolismo
2.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462013

RESUMO

SARS-CoV-2 is the cause of COVID-19. Since the outbreak and rapid spread of COVID-19, it has been apparent that the disease is having multi-organ system involvement. Still its effect in the endocrine system is not fully clear and data on cortisol dynamics in patients with COVID-19 are not yet available. SARS-CoV-2 can knock down the host's cortisol stress response. Here we present a case of a 51-year-old man vomiting for 10 days after having confirmed COVID-19 infection. He had hypotension and significant hyponatraemia. Work-up was done including adrenocorticotropic hormone stimulation test. He was diagnosed as suffering from adrenal insufficiency and started on steroids with subsequent improvement in both blood pressure and sodium level. COVID-19 can cause adrenal insufficiency. Clinicians must be vigilant about the possibility of an underlying relative cortisol deficiency in patients with COVID-19.


Assuntos
Insuficiência Adrenal/fisiopatologia , Hiponatremia/fisiopatologia , Hipotensão/fisiopatologia , Acidose/sangue , Acidose/fisiopatologia , Acidose/terapia , Insuficiência Adrenal/sangue , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/tratamento farmacológico , Hidratação , Glucocorticoides/uso terapêutico , Humanos , Hidrocortisona/sangue , Hiponatremia/sangue , Hiponatremia/terapia , Hipofosfatemia/sangue , Hipofosfatemia/fisiopatologia , Hipofosfatemia/terapia , Hipotensão/terapia , Masculino , Pessoa de Meia-Idade , Testes de Função Adreno-Hipofisária , Prednisolona/uso terapêutico , Vômito/fisiopatologia , Desequilíbrio Hidroeletrolítico/sangue , Desequilíbrio Hidroeletrolítico/fisiopatologia , Desequilíbrio Hidroeletrolítico/terapia
3.
Crit Care Resusc ; 22(3): 275-280, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32900336

RESUMO

OBJECTIVE: To help shape the design of a future double blind placebo-controlled randomised clinical trial of bicarbonate therapy for metabolic acidosis, based on opinions of intensive care clinicians in Australia and New Zealand. DESIGN: An online survey was designed, piloted and distributed electronically to members of the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG) mailing list. The survey sought to collect information about choice of placebo, method of bicarbonate administration, and acid-base monitoring. MAIN OUTCOME MEASURES: Responses to six questions in the following domains were sought: 1) solution to be used as placebo; 2) method of administration; 3) target of the intervention; 4) timing of arterial blood gases to monitor the intervention; 5) duration of therapy; and 6) rate of bolus therapy (if selected as the best option). RESULTS: One in every eight ANZICS CTG members completed the survey (118/880, 13.4%). Compound sodium lactate was the preferred solution for placebo (54/118, 45.8%), and continuous infusion of bicarbonate (80/118, 67.8%) was the most frequently selected method of administration. A pH > 7.30 was the preferred target (50/118, 42.4%), while monitoring with arterial blood gas analysis every 2 hours until the target is reached and then every 4 hours was the most favoured option (40/118, 33.9%). The preferred duration of therapy was until the target is achieved (53/118, 44.9%). CONCLUSIONS: This survey offers important insights into the preferences of Australian and New Zealand clinicians in regards to any future randomised controlled trial of bicarbonate therapy for metabolic acidosis in the critically ill.


Assuntos
Acidose/tratamento farmacológico , Bicarbonato de Sódio/uso terapêutico , Acidose/sangue , Austrália , Cálcio/sangue , Cuidados Críticos , Estado Terminal , Método Duplo-Cego , Humanos , Nova Zelândia , Bicarbonato de Sódio/efeitos adversos , Inquéritos e Questionários , Resultado do Tratamento
4.
Ann Biol Clin (Paris) ; 78(3): 323-328, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32540819

RESUMO

Ketosis is a metabolic situation involving an increase in blood and urine concentrations of ketones that, when prolonged, leads to acidosis. Moderate ketosis usually appears after a fast of a few hours, but its prolongation exposes to hyperketosis. Observation: A 25-year-old woman presented to the emergency department for cohercitive vomiting. She was fasting for a long time in a spiritual setting and had a restricted diet limited to water and vitamin supplements. Clinical and biological assessment was in favour of fasting ketoacidosis. Evolution was favorable with intravenous hydration, poly-ionic and micronutrient supplementation and a gradual resumption of oral feeding. Conclusion: We report the case of a patient with fasting ketoacidosis. Besides consequences of this ketoacidosis, the challenge was also in resuming oral feeding in order to avoid a potentially fatal inappropriate renutrition syndrome.


Assuntos
Jejum/efeitos adversos , Cetose/etiologia , Inanição/complicações , Acidose/sangue , Acidose/diagnóstico , Acidose/etiologia , Acidose/terapia , Adulto , Jejum/sangue , Feminino , Hidratação , Humanos , Cetose/sangue , Cetose/diagnóstico , Cetose/terapia , Nutrição Parenteral , Inanição/sangue , Inanição/terapia , Fatores de Tempo
5.
PLoS One ; 15(5): e0233851, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470084

RESUMO

Brain interstitial pH (pHbrain) alterations play an important role in the mechanisms of neuronal injury in neonatal hypoxic-ischemic encephalopathy (HIE) induced by perinatal asphyxia. The newborn pig is an established large animal model to study HIE, however, only limited information on pHbrain alterations is available in this species and it is restricted to experimental perinatal asphyxia (PA) and the immediate reventilation. Therefore, we sought to determine pHbrain over the first 24h of HIE development in piglets. Anaesthetized, ventilated newborn pigs (n = 16) were instrumented to control major physiological parameters. pHbrain was determined in the parietal cortex using a pH-selective microelectrode. PA was induced by ventilation with a gas mixture containing 6%O2-20%CO2 for 20 min, followed by reventilation with air for 24h, then the brains were processed for histopathology assessment. The core temperature was maintained unchanged during PA (38.4±0.1 vs 38.3±0.1°C, at baseline versus the end of PA, respectively; mean±SEM). In the arterial blood, PA resulted in severe hypoxia (PaO2: 65±4 vs 23±1*mmHg, *p<0.05) as well as acidosis (pHa: 7.53±0.03 vs 6.79±0.02*) that is consistent with the observed hypercapnia (PaCO2: 37±3 vs 160±6*mmHg) and lactacidemia (1.6±0.3 vs 10.3±0.7*mmol/L). Meanwhile, pHbrain decreased progressively from 7.21±0.03 to 5.94±0.11*. Reventilation restored pHa, blood gases and metabolites within 4 hours except for PaCO2 that remained slightly elevated. pHbrain returned to 7.0 in 29.4±5.5 min and then recovered to its baseline level without showing secondary alterations during the 24 h observation period. Neuropathological assessment also confirmed neuronal injury. In conclusion, in spite of the severe acidosis and alterations in blood gases during experimental PA, pHbrain recovered rapidly and notably, there was no post-asphyxia hypocapnia that is commonly observed in many HIE babies. Thus, the neuronal injury in our piglet model is not associated with abnormal pHbrain or low PaCO2 over the first 24 h after PA.


Assuntos
Encéfalo/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Acidose/sangue , Acidose/complicações , Acidose/metabolismo , Acidose/fisiopatologia , Animais , Animais Recém-Nascidos , Asfixia Neonatal/sangue , Asfixia Neonatal/metabolismo , Asfixia Neonatal/fisiopatologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Hemodinâmica , Concentração de Íons de Hidrogênio , Hipercapnia/sangue , Hipercapnia/complicações , Hipercapnia/metabolismo , Hipercapnia/fisiopatologia , Hipóxia-Isquemia Encefálica/sangue , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/fisiopatologia , Masculino , Neurônios/patologia , Oxigênio/metabolismo , Suínos
6.
PLoS One ; 15(4): e0230708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271786

RESUMO

Neonatal calf diarrhea (NCD) is a major problem to calf health worldwide, in terms of both morbidity and mortality. A five-point ordinal scale clinical assessment scoring (CAS) chart was utilized to assess calves suffering from NCD-related clinical abnormalities (acidosis and dehydration) on commercial farms. The objective of this research was to determine the predictive capability of this CAS chart against gold standard blood gas parameters, designed to assist farmers in the accurate assessment of the clinical consequences of NCD. A total of 443 diarrheic and non-diarrheic calves were enrolled in the study. The CAS chart rated a calf's health from no clinical signs to varying degrees of clinical severity on a 0 (clinically normal) to 4 (grave) scale, based on clinical indicators including calf demeanour, ear position, mobility, suckle reflex, desire-to-feed, and enophthalmos. Blood gas analysis was conducted for individual calves, consisting of pH, base excess, Na+, K+, Ca2+, Cl-, glucose, total hemoglobin, bicarbonate, anion gap, and strong ion difference. Statistical evaluation was performed by comparison of the CAS score with blood gas profiles using ordinal logistic regression and a non-parametric estimation of the Receiver Operating Characteristics (ROC). The ROC analysis indicated that the CAS chart had acceptable specificity (>95%) with low sensitivity (<60%) in differentiating clinically normal from acidotic/dehydrated cases. Assessment of individual severity classes indicated that the chart can predict and differentiate both clinically normal and advanced cases from the other severity classes (peak estimations >80%) but had reduced accuracy in differentiating mild and moderate cases (peak estimations >50%). The chart, as presented, provides a simple tool to differentiate clinically normal from calves suffering the consequences of diarrhea, but fails to accurately differentiate severity for NCD related acidosis and dehydration. Further efforts are required to enhance the sensitivity and differential diagnostic value of this type of chart.


Assuntos
Animais Recém-Nascidos , Doenças dos Bovinos/diagnóstico , Técnicas e Procedimentos Diagnósticos/veterinária , Diarreia/diagnóstico , Design de Software , Acidose/sangue , Acidose/diagnóstico , Acidose/veterinária , Animais , Gasometria/normas , Gasometria/veterinária , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/patologia , Desidratação/sangue , Desidratação/diagnóstico , Desidratação/veterinária , Técnicas e Procedimentos Diagnósticos/normas , Diarreia/sangue , Diarreia/patologia , Diarreia/veterinária , Feminino , Masculino , Valor Preditivo dos Testes , Prognóstico , Projetos de Pesquisa , Índice de Gravidade de Doença
7.
Ren Fail ; 42(1): 234-243, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32138574

RESUMO

Background: This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients' in-hospital clinical outcomes.Methods: Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database.Results: Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased.Conclusion: EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.


Assuntos
Desequilíbrio Ácido-Base/etiologia , Custos Hospitalares/estatística & dados numéricos , Mortalidade Hospitalar , Tempo de Internação/estatística & dados numéricos , Neoplasias/complicações , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Ácido-Base/sangue , Acidose/sangue , Acidose/etiologia , Idoso , Alcalose/sangue , Alcalose/etiologia , China , Feminino , Humanos , Hiperpotassemia/etiologia , Hipernatremia/etiologia , Hipocalcemia/etiologia , Hipopotassemia/etiologia , Hiponatremia/etiologia , Hipofosfatemia/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Desequilíbrio Hidroeletrolítico/sangue
8.
Kidney Blood Press Res ; 45(2): 263-274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32062662

RESUMO

INTRODUCTION: The kidneys play a central role in eliminating metabolic waste products and drugs through transporter-mediated excretion along the proximal tubule. This task is mostly achieved through a variety of transporters from the solute carrier family 22 (SLC22) family of organic cation and anion transporters. Metabolic acidosis modulates metabolic and renal functions and also affects the clearance of metabolites and drugs from the body. We had previously shown that induction of metabolic acidosis in mice alters a large set of transcripts, among them also many transporters including transporters from the Slc22 family. OBJECTIVE: Here we further investigated the impact of acidosis on Slc22 family members. METHODS: Metabolic acidosis was induced for 2 or 7 days with NH4Cl, some animals also received the uricase inhibitor oxonic acid for comparison. Expression of transporters was studied by qPCR and immunoblotting. RESULTS: NH4Cl induced no significant changes in plasma or urine uric acid levels but caused downregulation of Slc22a1 (Oct1), Slc22a6 (Oat1), Slc22a19 (Oat5), and -Slc22a12 (Urat1) at mRNA level. In contrast, Slc22a4 mRNA (Octn1) was upregulated. On protein level, NH4Cl increased Octn1 (after 7 days) and Urat1 (after 2 days) abundance and decreased Oat1 (after 2 days) and Urat1 (after 7 days). Oxonic acid had no impact on protein abundance of any of the transporters tested. CONCLUSION: In summary, metabolic acidosis alters expression of several transporters involved in renal excretion of metabolic waste products and drugs. This may have implications for drug kinetics and clearance of waste metabolites.


Assuntos
Acidose/metabolismo , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/biossíntese , Nefropatias/patologia , Acidose/sangue , Acidose/patologia , Acidose/urina , Animais , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/genética , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/metabolismo , Nefropatias/sangue , Nefropatias/metabolismo , Nefropatias/urina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 1 de Transcrição de Octâmero/biossíntese , Fator 1 de Transcrição de Octâmero/genética , Fator 1 de Transcrição de Octâmero/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ácido Úrico/sangue , Ácido Úrico/urina
9.
Pediatr Hematol Oncol ; 37(3): 245-247, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31984843

RESUMO

Acute lymphoblastic leukemia maintenance chemotherapy includes mercaptopurine, a purine analog with uncommon side effects, that can be life-threatening. We describe a 7-year-old female patient with ALL that presented with altered state of consciousness after maintenance chemotherapy with methotrexate and 6-mercaptopurine, due to severe hypoglycemia with metabolic acidosis. She initiated metabolic corrections with rapid resolution of symptoms. Hypoglycemia secondary to 6-mercaptopurine is a rare and transient side effect. The cause effect relation is difficult to establish, leading to underdiagnosis. Hypoglycemia is preventable without compromising maintenance therapy efficacy.


Assuntos
Acidose , Hipoglicemia , Mercaptopurina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Acidose/sangue , Acidose/induzido quimicamente , Acidose/diagnóstico , Criança , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemia/diagnóstico , Mercaptopurina/administração & dosagem , Mercaptopurina/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Índice de Gravidade de Doença
11.
Ann Pharmacother ; 54(6): 541-546, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31791136

RESUMO

Background: Increasing evidence suggests that large-volume infusions of 0.9% sodium chloride (NaCl) for resuscitation are associated with hyperchloremic metabolic acidosis, renal vasoconstriction, and increased risk of acute kidney injury (AKI). Patients with neurological injury may require hypertonic NaCl for therapeutic hypernatremia, treatment of cerebral salt wasting, hyponatremia, or elevated intracranial pressure. Consequently, this increased exposure to chloride may result in an increased risk for development of AKI. Objective: The primary aim of this study was to describe the risk for development of AKI in neurologically injured patients receiving large volumes of intravenous hypertonic NaCl. Methods: This single-center, retrospective study looked at neurologically injured patients who received hypertonic NaCl and sodium acetate. Data were collected to assess renal function, hyperchloremia, and acidemia. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive association between the amount of daily and overall chloride exposure and development of AKI. Results: A total of 301 patients were screened, and of those, 142 were included. Of the 142 patients included, 13% developed AKI, and 38% developed hyperchloremia. Additionally, 32% of patients were switched from NaCl to sodium acetate after an average of 3.4 ± 1.5 days of NaCl therapy. The ROC curve demonstrated that if patients received greater than 2055 mEq of chloride over 7 days, they were more likely to develop AKI (sensitivity 72%, specificity 70%; P = 0.002; area under the curve = 0.7). Conclusion and Relevance: Neurologically injured patients receiving hypertonic sodium therapy with a high chloride load are at risk of developing hyperchloremia and AKI.


Assuntos
Acidose/induzido quimicamente , Lesão Renal Aguda/induzido quimicamente , Ressuscitação/métodos , Cloreto de Sódio/efeitos adversos , Traumatismos do Sistema Nervoso/terapia , Acidose/sangue , Acidose/epidemiologia , Lesão Renal Aguda/sangue , Lesão Renal Aguda/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Solução Salina Hipertônica , Cloreto de Sódio/administração & dosagem , Cloreto de Sódio/sangue
12.
BJOG ; 127(3): 405-413, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31762140

RESUMO

OBJECTIVE: To determine variations in cord blood gas (CBG) parameters after 3-minute delayed cord clamping (DCC) in vaginal deliveries (VDs) and caesarean deliveries (CDs) at term without fetal distress. DESIGN: Prospective observational study. SETTING: University hospital. SAMPLE: CBG from 97 VDs and 124 CDs without fetal distress. METHODS: Comparison of paired arterial-venous CBG parameters drawn at birth from the unclamped cord and after 3-minutes DCC for VDs and CDs. MAIN OUTCOME MEASURES: Base excess, bicarbonate, haematocrit and haemoglobin from both arterial and venous cord blood, lactate, neonatal outcomes, partial pressure of oxygen (pO2 ), partial pressure of carbon dioxide (pCO2 ), pH, and postpartum haemorrhage. RESULTS: Arterial cord blood pH, bicarbonate ( HCO 3 - , mmol/l), and base excess (BE, mmol/l) decreased significantly after 3-minute DCC both in VDs (pH = 7.23 versus 7.27; P < 0.001; HCO 3 -  = 23.3 versus 24.3; P = 0.004; BE = -5.1 versus -2.9; P < 0.001) and CDs (pH = 7.28 versus 7.34; P < 0.001; HCO 3 -  = 26.2 versus 27.2; P < 0.001; BE = -1.5 versus 0.7; P < 0.001). After 3-minute DCC, pCO2 increased in CDs only (57 versus 51; P < 0.001), whereas lactate increased more in CDs compared with VDs (lactate, +1.1 [0.9, 1.45] versus +0.5 [-0.65, 2.35]; P = 0.01). Postpartum maternal haemorrhage, neonatal maximum bilirubin concentration, and need for phototherapy were similar between the two groups. Newborns born by CD more frequently required postnatal clinical monitoring or admission to a neonatal intensive care unit. CONCLUSIONS: After 3-minute DCC, the acid-base status shifted towards mixed acidosis in CDs and prevalent metabolic acidosis in VDs. CDs were associated with a more pronounced increase in arterial lactate, compared with VDs. TWEETABLE ABSTRACT: By 3-minute DCC, acid-base status shifts towards mixed and metabolic acidosis in caesarean and vaginal delivery, respectively.


Assuntos
Acidose , Cesárea , Parto Obstétrico , Sangue Fetal/metabolismo , Complicações do Trabalho de Parto , Cordão Umbilical/cirurgia , Acidose/sangue , Acidose/diagnóstico , Acidose/etiologia , Gasometria/métodos , Cesárea/efeitos adversos , Cesárea/métodos , Cesárea/estatística & dados numéricos , Constrição , Parto Obstétrico/efeitos adversos , Parto Obstétrico/métodos , Parto Obstétrico/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Itália/epidemiologia , Masculino , Complicações do Trabalho de Parto/diagnóstico , Complicações do Trabalho de Parto/epidemiologia , Complicações do Trabalho de Parto/etiologia , Gravidez , Resultado da Gravidez/epidemiologia , Tempo para o Tratamento
13.
Arch Gynecol Obstet ; 301(1): 137-142, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883047

RESUMO

PURPOSE: Phase-rectified signal averaging method (PRSA) represents an analysis method which applied on fetal cardiotocography (CTG) allows the quantification of the speed of fetal heart rate changes. By calculating the average deceleration capacity (ADC) an assessment of the fetal autonomic nervous system (ANS) is possible. The objective of this study was to test its ability to predict perinatal acidosis. METHODS: A case-control study was performed at a University Hospital in Munich. All intrapartum CTG heart rate tracings saved during a 7-year period were considered for analysis. All neonates born with an umbilical arterial blood pH ≤ 7.10 were considered as cases. Controls were defined as healthy fetuses born with a pH ≥ 7.25. The main matching criteria were gestational age at delivery, parity, birth mode, and birth weight percentile. Exclusion criteria were a planned caesarean section, fetal malformations, and multiple pregnancies. ADC and STV were then calculated during the last 60, the last 45, and the last 30 min intervals prior to delivery. RESULTS: Of all stored birth CTG recordings, 227 cases met the inclusion criteria and were studied. ADC was significantly higher in fetuses born with acidemia (4.85 bpm ± 3.0) compared to controls (3.36 bpm ± 2.2). The area under ROC curve was 0.659 (95% CI 0.608-0.710) for ADC and 0.566 (0.512-0.620) for STV (p = 0.013). CONCLUSIONS: This study confirms that the assessment of ADC using PRSA represents a good additional tool for the prediction of acute fetal acidosis during delivery.


Assuntos
Acidose/sangue , Cardiotocografia/métodos , Sangue Fetal/química , Doenças Fetais/diagnóstico , Estudos de Casos e Controles , Feminino , Sangue Fetal/citologia , Doenças Fetais/sangue , Frequência Cardíaca Fetal/fisiologia , Humanos , Masculino , Gravidez
14.
Anesth Analg ; 130(4): 1063-1076, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31609256

RESUMO

BACKGROUND: Coagulopathy and hemostatic abnormalities remain a challenge in patients following trauma and major surgery. Coagulopathy in this setting has a multifactorial nature due to tissue injury, hemodilution, hypothermia, and acidosis, the severity of which may vary. In this study, we combined computational kinetic modeling and in vitro experimentation to investigate the effects of multifactorial coagulopathy on thrombin, the central enzyme in the coagulation system. METHODS: We measured thrombin generation in platelet-poor plasma from 10 healthy volunteers using the calibrated automated thrombogram assay (CAT). We considered 3 temperature levels (31°C, 34°C, and 37°C), 3 pH levels (6.9, 7.1, and 7.4), and 3 degrees of dilution with normal saline (no dilution, 3-fold dilution, and 5-fold dilution). We measured thrombin-generation time courses for all possible combinations of these conditions. For each combination, we analyzed 2 scenarios: without and with (15 nM) supplementation of thrombomodulin, a key natural regulator of thrombin generation. For each measured thrombin time course, we recorded 5 quantitative parameters and analyzed them using multivariable regression. Moreover, for multiple combinations of coagulopathic conditions, we performed routine coagulation tests: prothrombin time (PT) and activated partial thromboplastin time (aPTT). We compared the experimental results with simulations using a newly developed version of our computational kinetic model of blood coagulation. RESULTS: Regression analysis allowed us to identify trends in our data (P < 10). In both model simulations and experiments, dilution progressively reduced the peak of thrombin generation. However, we did not experimentally detect the model-predicted delay in the onset of thrombin generation. In accord with the model predictions, hypothermia delayed the onset of thrombin generation; it also increased the thrombin peak time (up to 1.30-fold). Moreover, as predicted by the kinetic model, the experiments showed that hypothermia increased the area under the thrombin curve (up to 1.97-fold); it also increased the height of the thrombin peak (up to 1.48-fold). Progressive acidosis reduced the velocity index by up to 24%; acidosis-induced changes in other thrombin generation parameters were much smaller or none. Acidosis increased PT by 14% but did not influence aPTT. In contrast, dilution markedly prolonged both PT and aPTT. In our experiments, thrombomodulin affected thrombin-generation parameters mainly in undiluted plasma. CONCLUSIONS: Dilution with normal saline reduced the amount of generated thrombin, whereas hypothermia increased it and delayed the time of thrombin accumulation. In contrast, acidosis in vitro had little effect on thrombin generation.


Assuntos
Acidose/sangue , Transtornos da Coagulação Sanguínea/prevenção & controle , Hemodiluição/métodos , Hipotermia Induzida , Trombina/biossíntese , Adulto , Idoso , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Temperatura Corporal , Feminino , Voluntários Saudáveis , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Adulto Jovem
15.
Clin Chim Acta ; 500: 172-179, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669932

RESUMO

BACKGROUND: Anion gap (AG) aids the differential diagnosis of acid-base disorders. Its value has decreased, because of new analytical methods. Our goal was to compare AG reference intervals for different instruments and Southeast Asian populations. METHODS: We studied AG at three hospitals. One used the cobas 8000; two others, the Architect c16000. We included consecutive adults ≥18 years whose samples were sent for electrolytes and creatinine. We assessed AG for all patients and patients with normal electrolytes. RESULTS: AG means differed significantly (P < 0.001) between the three hospitals for all patients and the normal electrolyte subgroup. AG reference intervals from all patients were 9-19, 5-15, and 5-15 mmol/L, and for the normal electrolyte subgroup, 10-17, 6-14, and 5-12 mmol/L, respectively. Compared to the normal albumin group, hypoalbuminemia patients showed lower AG in two hospitals (P < 0.001, P = 0.03), whereas patients with hyperalbuminemia demonstrated higher AG in all three hospitals (P < 0.001). CONCLUSIONS: Different instruments produce different AGs. There is a weak correlation between albumin levels and AG. Laboratorians should verify reference intervals used when detecting laboratory errors and assisting clinicians in the differential diagnosis of acid base disorders and other medical conditions.


Assuntos
Acidose/sangue , Análise Química do Sangue/normas , Albumina Sérica/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Adulto Jovem
16.
Exp Neurol ; 323: 113078, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31697942

RESUMO

INTRODUCTION: Ischemic stroke is the one of the most severe and debilitating diseases, and despite animal models, there is much to learn about the neuropathology in humans in a way that could inform the development of therapies. We have developed a protocol to collect and evaluate arterial blood immediately distal and proximal from the removed intracranial thrombus during mechanical thrombectomy. These samples provide a unique resource in evaluating acute changes in acid/base and electrolyte concentrations at the time of ischemic stroke. The purpose of this study was to compare acid/base and electrolytes obtained proximal and distal to the occluded intracranial thrombi between male and female acute ischemic stroke subjects at the time of thrombectomy; and to determine whether arterial blood gas values predict outcomes in male and female subjects. METHODS: We analyzed the first 49 subjects (age = 67 ±â€¯15.0, 21 males) in the BACTRAC registry. We compared arterial blood gas of blood distal versus proximal to the thrombus during thrombectomy which provided acid/base levels (pH, pCO2, pO2, BD, HCO3-) and electrolyte values (iCa2+, K+, and Na+). Comparisons were evaluated by one-way repeated measures ANOVA (p < .05). Moderated multiple regression with an interaction term of sex determined predictors of infarct volume, edema volume, and infarct time. RESULTS: In general, distal intracranial luminal blood sample showed a compensated metabolic acidosis with an elevated oxygen concentration in both blood samples. Analysis indicated several significant differences in the proximal blood samples between sexes (pH, pCO2, and K+). Bicarbonate and base deficit were predictors of infarct time specifically in female subjects. DISCUSSION AND CONCLUSION: Acid/base and electrolyte response to ischemic conditions differ between men and women, and these early changes could be used to predict local acid/base changes and how they develop differently in men and women during ischemia. These findings provide a novel insight into the pathology of large vessel stroke in humans, particularly potential variations based on sex.


Assuntos
Acidose/sangue , Gasometria , Eletrólitos/sangue , Caracteres Sexuais , Acidente Vascular Cerebral/sangue , Ácidos/sangue , Idoso , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/cirurgia , Trombectomia
17.
Am J Respir Crit Care Med ; 201(7): 799-813, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31553891

RESUMO

Rationale: Acidemia is a severe condition among critically ill patients. Despite lack of evidence, sodium bicarbonate is frequently used to correct pH; however, its administration is burdened by several side effects. We hypothesized that the reduction of plasma chloride concentration could be an alternative strategy to correct acidemia.Objectives: To evaluate feasibility, safety, and effectiveness of a novel strategy to correct acidemia through extracorporeal chloride removal by electrodialysis.Methods: Ten swine (six treated and four control animals) were sedated, mechanically ventilated and connected to an extracorporeal electrodialysis device capable of selectively removing chloride. In random order, an arterial pH of 7.15 was induced either through reduction of ventilation (respiratory acidosis) or through lactic acid infusion (metabolic acidosis). Acidosis was subsequently sustained for 12-14 hours. In treatment pigs, soon after reaching target acidemia, electrodialysis was started to restore pH.Measurements and Main Results: During respiratory acidosis, electrodialysis reduced plasma chloride concentration by 26 ± 5 mEq/L within 6 hours (final pH = 7.36 ± 0.04). Control animals exhibited incomplete and slower compensatory response to respiratory acidosis (final pH = 7.29 ± 0.03; P < 0.001). During metabolic acidosis, electrodialysis reduced plasma chloride concentration by 15 ± 3 mEq/L within 4 hours (final pH = 7.34 ± 0.07). No effective compensatory response occurred in control animals (final pH = 7.11 ± 0.08; P < 0.001). No complications occurred.Conclusions: We described the first in vivo application of an extracorporeal system targeted to correct severe acidemia by lowering plasma chloride concentration. Extracorporeal chloride removal by electrodialysis proved to be feasible, safe, and effective. Further studies are warranted to assess its performance in the presence of impaired respiratory and renal functions.


Assuntos
Acidose/sangue , Acidose/terapia , Cloretos/sangue , Diálise Renal/métodos , Animais , Eletricidade , Circulação Extracorpórea , Suínos
18.
J Formos Med Assoc ; 119(2): 644-651, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31493983

RESUMO

BACKGROUND: Resuscitation guidelines list acidaemia as a potentially reversible cause of cardiac arrest without specifying the threshold defining acidaemia. We examined the association between early intra-arrest arterial blood gas (ABG) data and outcomes of in-hospital cardiac arrest (IHCA). METHODS: This single-centred retrospective study reviewed patients with IHCA between 2006 and 2015. Early intra-arrest ABG data were measured within 10 min of initiating cardiopulmonary resuscitation. The ABG analysis included measurements of blood pH, PaCO2, and HCO3-. RESULTS: Among the 1065 included patients, 60 (5.6%) achieved neurologically intact survival. Mean blood pH was 7.2. Mean PaCO2 and HCO3- levels were 59.7 mmHg and 22.1 mmol/L, respectively. A blood pH of 7.2 was identified by a generalised additive models plot to define severe acidaemia. The PaCO2 level was higher in patients with severe acidaemia (mean: 74.5 vs. 44.1 mmHg) than in those without. Multivariable logistic regression analyses indicated that blood pH > 7.2 was associated with a favourable neurological recovery (odds ratio [OR]: 2.79, 95% confidence interval [CI]: 1.43-5.46; p-value = 0.003) and blood pH was positively associated with survival at hospital discharge (OR: 5.80, 95% CI: 1.62-20.69; p-value = 0.007). CONCLUSION: Early intra-arrest blood pH was associated with IHCA outcomes, while levels of PaCO2 and HCO3- were not. A blood pH of 7.2 could be used as the threshold defining severe acidaemia during arrest and help profile patients with IHCA. Innovative interventions should be developed to improve the outcomes of patients with severe acidaemia, such as novel ventilation methods.


Assuntos
Acidose/sangue , Gasometria , Reanimação Cardiopulmonar , Parada Cardíaca/sangue , Alta do Paciente/estatística & dados numéricos , Acidose/mortalidade , Acidose/fisiopatologia , Adulto , Idoso , Bicarbonatos/sangue , Dióxido de Carbono/sangue , Feminino , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Mortalidade Hospitalar , Humanos , Concentração de Íons de Hidrogênio , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Taxa de Sobrevida , Taiwan/epidemiologia
19.
J Matern Fetal Neonatal Med ; 33(3): 404-409, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29945485

RESUMO

Introduction: The intrapartum cardiotocography (CTG) classification system by FIGO in 2015 (FIGO2015) was introduced to simplify CTG interpretation, but it is not harmonized with the fetal ECG ST analysis (STAN) algorithm from 2007 (STAN2007), which is based on the FIGO CTG system from 1987. The study aimed to determine time courses and sensitivity between the systems in classifying CTG + ST events to indicate metabolic acidosis at birth.Material and methods: Forty-four cases with umbilical cord artery metabolic acidosis were retrieved from a European multicenter database. CTG patterns and timing of the first occurring significant ST events were evaluated post hoc in consensus by an expert panel and sensitivity statistics were performed. Wilcoxon's matched-pairs signed-ranks test and McNemar's test were used with a two-tailed p < .05 regarded significant.Results: STAN2007 had a higher sensitivity (73 versus 43%, p = .0002) and alarmed for metabolic acidosis in mean 34 min earlier than the FIGO2015 system did (p = .002). In every fourth case, the time difference was ≥20 min.Conclusions: In this simulation study, surveillance with STAN2007 combined with fetal ECG ST analysis had a significantly higher sensitivity and would have alarmed for metabolic acidosis significantly earlier than the new FIGO system would have.


Assuntos
Acidose/diagnóstico , Cardiotocografia , Acidose/sangue , Eletrocardiografia , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Masculino
20.
Pediatr Emerg Care ; 36(3): e143-e145, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28742636

RESUMO

INTRODUCTION: Hyperchloremic metabolic acidosis can occur in diabetic ketoacidosis (DKA) and may affect the acid-base interpretation during treatment. OBJECTIVES: This study aims to describe the prevalence of hyperchloremia during the treatment of DKA and its effect on the interpretation of bicarbonate value. METHODS: A cross-sectional study, including all cases of DKA in patients aged 1 to 18 years old admitted from 2010 to 2015, was performed. Laboratory tests were performed on admission (baseline), 2 and 6 hours after admission, and when resolution of DKA was achieved. Adjusted bicarbonate value was calculated using regression equations. RESULTS: Seventy-nine DKA episodes were included. The average age was 13.3 ± 3.8 years. Baseline levels were as follows: plasma glucose, 479 ± 133 mg/dL; pH 7.1 ± 0.083; bicarbonate, 9.65 ± 2.9; and anion gap, 23.9 ± 7.5. The time to achieve resolution of DKA was 12.2 ± 4.4 hours, and the decrease in capillary glucose was 25.5 (19.7-38.2) mg/dL per hour. After 6 hours of treatment, the proportion of patients presenting hyperchloremia increased from 23% to 77%. By using adjusted bicarbonate, the percentage of patients achieving resolution of DKA after 6 hours of treatment would have been 35.4% (confidence interval 95%, 28-49), in comparison with 24.1% (confidence interval 95%, 18-37) using observed bicarbonate (P = 0.004). CONCLUSIONS: The hyperchloremia developed during the treatment of DKA could modify the value of measured plasma bicarbonate concentration and unnecessarily prolong the initial phase of treatment.


Assuntos
Acidose/sangue , Acidose/epidemiologia , Bicarbonatos/sangue , Cetoacidose Diabética/sangue , Cetoacidose Diabética/tratamento farmacológico , Cloreto de Sódio/administração & dosagem , Equilíbrio Ácido-Base , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Prevalência
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