Efficacy and safety of terlipressin and albumin vs. noradrenaline and albumin in adult patients with hepatorenal syndrome: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Hepatorenal syndrome (HRS) is a serious complication of cirrhosis treated with various medications. We aim to evaluate terlipressin and albumin's effectiveness and safety compared to albumin and noradrenaline in adult hepatorenal disease patients. MATERIALS AND METHODS: Clinical trials from four databases were included. Cochrane's approach for calculating bias risk was utilized. We rated the quality evaluation by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included the following outcomes: serum creatinine (mg/dl), urine output (ml/24 h), mean arterial pressure (mmHg), reversal rate of HRS, mortality rate, blood plasma renin activity (ng/ml/h), plasma aldosterone concentration (pg/ml), urine sodium (mEq/l), and creatinine clearance (ml/min). RESULTS: Our analysis of nine clinical studies revealed that the noradrenaline group was associated with higher creatinine clearance (MD = 4.22 [0.40, 8.05]), (P = 0.03). There were no significant differences in serum creatinine levels (MD = 0.03 [-0.07, 0.13]), urinary sodium (MD = -1.02 [-5.15, 3.11]), urine output (MD = 32.75 [-93.94, 159.44]), mean arterial pressure (MD = 1.40 [-1.17, 3.96]), plasma renin activity (MD = 1.35 [-0.17, 2.87]), plasma aldosterone concentration (MD = 55.35 [-24.59, 135.29]), reversal rate of HRS (RR = 1.15 [0.96, 1.37]), or mortality rate (RR = 0.87 [0.74, 1.01]) between the two groups (p-values > 0.05). CONCLUSIONS: Noradrenaline is a safe alternative medical therapy for HRS.

Administration of methylene blue in septic shock: pros and cons.

Septic shock typically requires the administration of vasopressors. Adrenergic agents remain the first choice, namely norepinephrine. However, their use to counteract life-threatening hypotension comes with potential adverse effects, so that non-adrenergic vasopressors may also be considered. The use of agents that act through different mechanisms may also provide an advantage. Nitric oxide (NO) is the main driver of the vasodilation that leads to hypotension in septic shock, so several agents have been tested to counteract its effects. The use of non-selective NO synthase inhibitors has been of questionable benefit. Methylene blue, an inhibitor of soluble guanylate cyclase, an important enzyme involved in the NO signaling pathway in the vascular smooth muscle cell, has also been proposed. However, more than 25 years since the first clinical evaluation of MB administration in septic shock, the safety and benefits of its use are still not fully established, and it should not be used routinely in clinical practice until further evidence of its efficacy is available.

Terlipressin in combination with albumin as a therapy for hepatorenal syndrome in patients aged 65 years or older.

INTRODUCTION AND OBJECTIVES: Clinical data for older patients with advanced liver disease are limited. This post hoc analysis evaluated the efficacy and safety of terlipressin in patients aged ≥65 years with hepatorenal syndrome using data from 3 Phase III, randomized, placebo-controlled studies (OT-0401, REVERSE, CONFIRM). PATIENTS AND METHODS: The pooled population of patients aged ≥65 years (terlipressin, n = 54; placebo, n = 36) was evaluated for hepatorenal syndrome reversal-defined as a serum creatinine level ≤1.5 mg/dL (≤132.6 µmol/L) while receiving terlipressin or placebo, without renal replacement therapy, liver transplantation, or death-and the incidence of renal replacement therapy (RRT). Safety analyses included an assessment of adverse events. RESULTS: Hepatorenal syndrome reversal was almost 2-times higher in terlipressin-treated patients compared with patients who received placebo (31.5% vs 16.7%; P = 0.143). Among surviving patients, the need for RRT was significantly reduced in the terlipressin group, with an almost 3-times lower incidence of RRT versus the placebo group (Day 90: 25.0% vs 70.6%; P = 0.005). Among 23 liver-transplant-listed patients, significantly fewer patients in the terlipressin versus placebo group needed RRT by Days 30 and 60 (P = 0.027 each). Fewer patients in the terlipressin group needed RRT post-transplant (P = 0.011). More terlipressin-treated patients who were listed for and received a liver transplant were alive and RRT-free by Day 90. No new safety signals were revealed in the older subpopulation compared with previously published data. CONCLUSIONS: Terlipressin therapy may lead to clinical improvements in highly vulnerable patients aged ≥65 years with hepatorenal syndrome. CLINICAL TRIAL NUMBERS: OT-0401, NCT00089570; REVERSE, NCT01143246; CONFIRM, NCT02770716.

Incidence of bradycardia during noradrenaline or phenylephrine bolus treatment of postspinal hypotension in cesarean delivery: A randomized double-blinded controlled trial.

The treatment of choice for spinal anesthesia-induced hypotension during cesarean section is phenylephrine. As this vasopressor can cause reflex bradycardia, noradrenaline is a suggested alternative. This randomized double-blinded controlled trial included 76 parturients undergoing elective cesarean delivery under spinal anesthesia. Women received noradrenaline in bolus doses of 5 mcg or phenylephrine in bolus doses of 100 mcg. These drugs were used intermittently and therapeutically to maintain systolic blood pressure ≥ 90% of its baseline value. The primary study outcome was bradycardia incidence (<60 bpm) with intermittent bolus administration of these drugs. Secondary outcomes included extreme bradycardia (<40 bpm), number of bradycardia episodes, hypertension (systolic blood pressure > 120% of baseline value), and hypotension (systolic blood pressure < 90% of baseline value and requiring vasopressor use). Neonatal outcomes per the Apgar scale and umbilical cord blood gas analysis were also compared. The incidence of bradycardia in both groups (51.4% and 70.3%, respectively; p = 0.16) were not significantly different. No neonates had umbilical vein or artery pH values below 7.20. The noradrenaline group required more boluses than phenylephrine group (8 vs. 5; p = 0.01). There was no significant intergroup difference in any of the other secondary outcomes. When administered in intermittent bolus doses for the treatment of postspinal hypotension in elective cesarean delivery, noradrenaline, and phenylephrine have a similar incidence of bradycardia. When treating hypotension related to spinal anesthesia in obstetric cases, strong vasopressors are commonly administered, thought these can also have side effects. This trial assessed bradycardia after bolus administration of noradrenaline or phenylephrine, and found no difference in risk for clinically meaningful bradycardia.

Avaliação dos padrões cardiovasculares e da concentração sérica de catecolaminas em pacientes submetidos à exodontias por via alveolar, sob anestesia local com epinefrina: um ensaio clínico controlado, cego e randomizado / Assessment of cardiovascular patterns and serum catecholamine concentration in patients undergoing alveolar extraction under local anesthesia with epinephrine: a controlled, blind and randomized clinical trial

Objetivos: Um ensaio clínico controlado, cego e randomizado foi desenvolvido para avaliar os efeitos cardiovasculares em pacientes saudáveis e com hipertensão submetidos à exodontia por via alveolar utilizando lidocaína com epinefrina 1:100.000. Materiais e métodos: Vinte pacientes foram divididos em grupos experimental (GE ­ pacientes hipertensos) e controle (GC ­ pacientes normotensos). As variáveis analisadas foram a frequência cardíaca (FC), saturação de oxigênio (SO2), pressão arterial sistólica e diastólica (PAsis e PAdias), concentração sérica de catecolaminas (dopamina, epinefrina e norepinefrina), extrassístoles ventriculares e supraventriculares (ESV e ESSV respectivamente) e depressão do segmento do ST. Os dados foram colhidos em três momentos distintos: inicial, transoperatório (trans) e final. Amostras de sangue foram coletadas para a mensuração das catecolaminas, e um aparelho de Holter foi utilizado para coleta de dados do eletrocardiograma incluindo um período de avaliação de 24 horas pós-operatório. Foram utilizados o teste de Mann-Whitney para identificar diferenças entre os grupos e o teste de Friedman com o pós-teste de Wilcoxon ajustado para a avaliação intragrupos das amostras repetidas. Resultados: O GE apresentou menor SO2 no momento inicial (p = 0,001) enquanto a PAsis apresentou diferença estatística para os três momentos de avaliação com o GE apresentando os maiores valores. As ESV foram maiores para o GE no período de avaliação pós-operatória de 24 horas (p = 0,041). As ESSV e as catecolaminas séricas foram similares nos dois grupos. A análise intragrupo revelou diferença significativa na avaliação da PAsis para o GE com o período trans operatório apresentando os maiores valores. Já avaliação das extrassístoles demonstrou que o período pós-operatório de 24 horas teve a maioria dos eventos sendo que apenas o GC não apresentou diferença significativa para a variável ESV durante esse período (p = 0,112). Não houve depressão do segmento ST para nenhum dos grupos, ou seja, a isquemia do miocárdio não foi observada durante o estudo. Conclusões: As exodontias por via alveolar, com o uso de ALVC com epinefrina podem ser realizadas de forma segura em pacientes hipertensos. A pressão arterial sistêmica deve ser monitorada durante todo o procedimento, sobretudo nos pacientes hipertensos, devido à tendência de aumento da pressão arterial nesses pacientes. Já o nível sérico de catecolaminas não sofre alteração nas condições estudadas assim como o uso de ALVC parecem não influenciar os padrões cardiovasculares nesse tipo de cirurgia (AU).

Objectives: A blind, randomized controlled clinical trial was developed to evaluate the cardiovascular effects of local anesthetics with vasoconstrictors (LAVC) containing epinephrine in healthy and hypertensive patients undergoing teeth extraction with lidocaine 2% with epinephrine 1:100.000. Materials and methods: 20 patients were divided into control (CG ­ normotensive patients) and experimental groups (EG ­ hypertensive patients). The variables analyzed were heart rate (HR), oxygen saturation (O2S), systolic and diastolic blood pressure (sysBP and diasBP), serum catecholamines concentration (dopamine, epinephrine, and norepinephrine), ventricular and supraventricular extrasystoles (VES and SVES respectively), and ST segment depression. Data was obtained in three different moments (initial, trans and final). Blood samples were taken to measure the catecholamines and a Holter device was used to measure data from the electrocardiogram including a 24-hour postoperative evaluation period. The Mann-Whitney test was used to identify differences between the two groups and the Friedman test with the adjusted Wilcoxon post-test were used for intragroup evaluation for repeated measures. Results: The EG presented a lower O2S in the initial period (p = 0,001) while the sysBP showed a statistical difference for the three evaluation periods with the EG presenting the highest values. The VES where higher for the EG during the 24-hour postoperative evaluation period (p = 0,041). The SVES and the serum catecholamines showed were similar between the groups. The intragroup analysis revealed significant statistical difference for the sysBP in the EG with the trans period presenting the highest measurements. The extrasystoles evaluation showed that the 24- hour postoperative period presented most events with only the CG not presenting statistical difference for the variable VES during this period (p = 0,112). No ST segment depression was noticed for both groups, ie, Myocardial ischemia was not observed. Conclusions: Teeth extraction with LAVC containing epinephrine can be safely executed in hypertensive patients. Blood pressure should be monitored during the entire procedure, especially in hypertensive patients due to a tendency to high blood pressure within these patients. Serum catecholamines concentration levels are not altered in the conditions seen in this study and the use of LAVC seem not to influence cardiovascular changes in this type of surgery (AU).

Per-operative fluid therapy, vasopressor and transfusion rate in DIEP-flap breast reconstruction. A series of cases / Fluidoterapia, uso de vasopresores y tasa transfusional peroperatoria en la reconstrucción mamaria con colgajo DIEP. Una serie de casos

OBJECTIVE: Anesthetic management in DIEP-flap breast reconstruction surgery may influence the appearance of postoperative complications. Fluid therapy, vasopressor use, and blood management are controversial. The aim was to audit hemodynamic management and to assess its impact on perioperative outcomes. MATERIAL AND METHODS: Sixty-seven cases of DIEP-flap breast reconstruction were reviewed. Data collected: anthropometric data; ASA score; comorbidities; timing of reconstruction (immediate/delayed), type of reconstruction (unilateral/bilateral); length of surgery; per-operative complications; per-operative fluid therapy, use of vasopressors, transfusion rate; re-intervention requirements; surgical success rate; hospital stay, and readmission rate. RESULTS: Median crystalloid infusion rate was 3.18 (2.63-3.76) ml/kg/h in the first 24 hours. Intraoperatively, colloids were administered in 35 (52%) patients at a median infusion rate of 1.40 (1.08-1.86) ml/Kg/h; 21 (60%) of them presented some postoperative complication. Hypotensive events were registered in 13 (19%) patients; 9 (69%) suffered some postoperative complication. The only vasopressor used was Ephedrine in 14 (21%) patients, at a median dose of 0 (0-6) mg. Red blood cell (RBC) transfusion was required in 18 (27%) patients. All of the patients who were transfused, 11 (61%) presented some postoperative complication. Hospital stay was 7 (7-9) days. Surgery was successful in 46 (69%) patients and readmission was necessary in 11 (16%) patients. CONCLUSIONS: Colloids administration, intraoperative hypotensive events, RBC transfusion, and delayed surgery are variables that could increase the risk of postoperative complications in our series.

OBJETIVO: El manejo anestésico en la cirugía de reconstrucción mamaria con colgajo DIEP podría influir en la aparición de complicaciones posoperatorias. La fluidoterapia, el uso de vasopresores y la tasa transfusional son motivo de controversia. Nuestro objetivo fue auditar el manejo hemodinámico y valorar su impacto en los resultados perioperatorios. MATERIAL Y MÉTODOS: Analizamos 67 pacientes programadas para reconstrucción mamaria con colgajo DIEP. Datos registrados: antropométricos; ASA; comorbilidades; momento de la reconstrucción (inmediata/diferida); tipo de reconstrucción (unilateral/bilateral); duración quirúrgica; complicaciones perioperatorias; fluidoterapia, vasopresores y tasa transfusional peroperatorios; tasa de reintervención, reingresos y éxito de la cirugía; estancia hospitalaria. RESULTADOS: La velocidad promedio de infusión de cristaloides fue de 3,18 (2,63-3,76) ml/kg/h en las primeras 24 h. Intraoperatoriamente se administraron coloides en 35 (52%) pacientes a una velocidad promedio de infusión de 1,40 (1,08-1,86) ml/kg/h, presentando complicaciones posoperatorias en 21 (60%) casos. Trece (19%) pacientes presentaron eventos hipotensivos intraoperatorios, registrándose complicaciones en 9 (69%). El único vasopresor utilizado fue la efedrina en 14 (21%) pacientes, a una dosis mediana de 0 (0-6) mg. Requirieron transfusión sanguínea 18 (27%) pacientes. Del total de pacientes transfundidos, 11 (61%) habían presentado alguna complicación posoperatoria. La cirugía fue un éxito en 46 (69%) casos. La estancia hospitalaria fue de 7 (7-9) días y el reingreso fue necesario en 11 (16%) casos. CONCLUSIONES: La administración de coloides, los eventos hipotensivos intraoperatorios, la transfusión de hemoderivados y la cirugía con reconstrucción tardía son variables que podrían incrementar el riesgo de complicaciones posoperatorias.

Effects of vasoconstrictor use on digital nerve block: systematic review with meta-analysis. / Efeitos do uso de vasoconstritores no bloqueio de nervos digitais: revisão sistemática com metanálise.

Conventionally, the association of local anesthetics with vasoconstrictors is avoided at extremities due to the risk of ischemia. However, recent studies suggest that there is safety in the use of vasoconstrictors at extremities. Thus, we sought to evaluate the effectiveness and safety of vasoconstrictor use combined with local anesthetics in digital nerve block compared to the use of anesthetics without vasoconstrictors, through a systematic review with meta-analysis of randomized clinical trials. Until May 2019 we searched MEDLINE, LILACS, SciELO, ScienceDirect, Scopus, ClinicalTrials.gov, and gray literature databases, without date or language restrictions. The keywords were the following: digital block, vasoconstrictor, and ischemia. We included randomized clinical trials in which there was the use of local anesthetics with associated or not with vasoconstrictors in digital blocks. In the primary variables, the occurrence of ischemic complications and the duration of anesthesia were analysed; in the secondary variables, the need for anesthetic reapplication, bleeding control, and latency were observed. Ten studies were included in this review. The occurrence of ischemia was not observed, regardless of the use of vasoconstrictors or not. The use of vasoconstrictors at a concentration of 1:100,000 or less was associated with longer anesthesia duration (P<0.00001), lower need for anesthetic reapplication (P=0.02), lower need for bleeding control (P=0.00006), and lower latency (P<0.00001). We could conclude that the use of vasoconstrictors associated with local anesthetics in digital block proved to be a safe and effective technique.

Convencionalmente, a associação de anestésicos locais com vasoconstritores é evitada em extremidades pelo risco de isquemia. Entretanto, estudos recentes sugerem haver segurança no uso de vasoconstritor em extremidades. Procuramos, assim, avaliar a efetividade e segurança do uso de vasoconstritores combinados com anestésicos locais no bloqueio de nervos digitais em comparação ao uso de anestésicos plenos, através de uma revisão sistemática com metanálise de ensaios clínicos randomizados. Pesquisamos, até maio de 2019, nas bases de dados MEDLINE, LILACS, SciELO, ScienceDirect, Scopus, ClinicalTrials.gov e literatura cinzenta, sem restrições de data ou idioma, os descritores: bloqueio digital, vasoconstritor e isquemia. Foram incluídos ensaios clínicos randomizados nos quais houve a utilização de anestésicos locais associados ou não a vasoconstritores em bloqueios digitais. Nas variáveis primárias foram analisadas a ocorrência de complicações isquêmicas e a duração da anestesia, e nas variáveis secundárias foram observadas necessidade de reaplicação anestésica, de controle de sangramento e latência. Dez estudos foram incluídos nesta revisão. Não foi observada a ocorrência de isquemia, independente do uso ou não de vasoconstritores. O uso de vasoconstritores na concentração de 1:100.000 ou menor esteve associado a maior duração da anestesia (P<0,00001), menor necessidade de reaplicação anestésica (P=0,02), menor necessidade de controle de sangramento (P=0,00006) e menor latência (P<0,00001). Pudemos concluir que uso de vasoconstritores associados a anestésicos locais no bloqueio digital mostrou-se uma técnica segura e efetiva.

Vasoconstrictors in hepatorenal syndrome - A critical review.

Hepatorenal syndrome has the worst prognosis among causes of acute kidney injury in cirrhotic patients. Its definitive treatment is liver transplantation. Nevertheless, considering its high short-term mortality rate and the shortage of liver grafts, a pharmacological treatment is of utmost importance, serving as a bridge to liver transplant. The clinical management of hepatorenal syndrome is currently based on the use of a vasoconstrictor in association with albumin. Terlipressin, noradrenaline and the combination of midodrine and octreotide could be used to treat hepatorenal syndrome. Among these options, terlipressin seems to gather the strongest body of evidence regarding efficacy and should be considered the first line of treatment whenever available and in the absence of contraindications. Treatment with a vasoconstrictor and albumin should be promptly initiated after the diagnosis of hepatorenal syndrome in order for patients to have higher chances of recovery.

Spectrum of acute kidney injury associated with cocaine use: report of three cases.

BACKGROUND: The consequences of cocaine use are multisystemic, such as, for instance, renal failure, hepatotoxicity and pulmonary toxicity, with renal alterations being the focus of the present study. The use of substances that modify the base composition of cocaine (or adulterants) aiming to potentiate its effects also has an impact on these manifestations. The present study aims to report three cases with different diagnosis of acute kidney injury related to cocaine use. CASE PRESENTATION: Case 01 - A 30-year-old female patient, who regularly used cocaine, started to have lower-limb edema, which showed a progressive and ascending evolution, affecting the face a few days later, associated with an isolated febrile episode and oligoanuria. The presence of cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA) was verified: reactive 1:80, with renal biopsy compatible with rapidly progressive glomerulonephritis (RPGN). Case 02 - A 34-year-old female patient, with difficult-to-control hypertension and a frequent user of cocaine, showed generalized sudden edema together with diffuse and progressive pruritus associated with oliguria, fever, nausea, and vomiting. Schistocyte screening was positive, with negative direct Coombs test, and negative serologies for hepatitis B, C and HIV, as well as negative anti-double-stranded DNA, Anti-SSA and Anti-SSB. The renal biopsy was compatible with thrombotic microangiopathy, associated with moderate interstitial fibrosis and acute tubular necrosis Case 03 - A 25-year-old male patient who had been a cocaine user for 5 years had a sudden onset of generalized disabling myalgia (especially in the lower limbs) associated with recent frontotemporal headache, palpitation, dizziness, and a non-measured febrile episode; the patient had used cocaine at the night before symptom onset. CPK was 1731 U/L.The final probable diagnosis was AKI secondary to cocaine-induced rhabdomyolysis. CONCLUSIONS: In conclusion basically, 05 etiologies of acute kidney injury should always be remembered: rhabdomyolysis, thrombotic microangiopathy, vasculitis, acute interstitial nephritis and renal infarction. Emphasis should be given to rhabdomyolysis due to its higher prevalence. Considering the increasing rates of cocaine use, especially with the use of adulterating substances, these pathologies will likely be increasingly prevalent.

Efeitos do uso de vasoconstritores no bloqueio de nervos digitais: revisão sistemática com metanálise / Effects of vasoconstrictor use on digital nerve block: systematic review with meta-analysis

RESUMO Convencionalmente, a associação de anestésicos locais com vasoconstritores é evitada em extremidades pelo risco de isquemia. Entretanto, estudos recentes sugerem haver segurança no uso de vasoconstritor em extremidades. Procuramos, assim, avaliar a efetividade e segurança do uso de vasoconstritores combinados com anestésicos locais no bloqueio de nervos digitais em comparação ao uso de anestésicos plenos, através de uma revisão sistemática com metanálise de ensaios clínicos randomizados. Pesquisamos, até maio de 2019, nas bases de dados MEDLINE, LILACS, SciELO, ScienceDirect, Scopus, ClinicalTrials.gov e literatura cinzenta, sem restrições de data ou idioma, os descritores: bloqueio digital, vasoconstritor e isquemia. Foram incluídos ensaios clínicos randomizados nos quais houve a utilização de anestésicos locais associados ou não a vasoconstritores em bloqueios digitais. Nas variáveis primárias foram analisadas a ocorrência de complicações isquêmicas e a duração da anestesia, e nas variáveis secundárias foram observadas necessidade de reaplicação anestésica, de controle de sangramento e latência. Dez estudos foram incluídos nesta revisão. Não foi observada a ocorrência de isquemia, independente do uso ou não de vasoconstritores. O uso de vasoconstritores na concentração de 1:100.000 ou menor esteve associado a maior duração da anestesia (P<0,00001), menor necessidade de reaplicação anestésica (P=0,02), menor necessidade de controle de sangramento (P=0,00006) e menor latência (P<0,00001). Pudemos concluir que uso de vasoconstritores associados a anestésicos locais no bloqueio digital mostrou-se uma técnica segura e efetiva.

ABSTRACT Conventionally, the association of local anesthetics with vasoconstrictors is avoided at extremities due to the risk of ischemia. However, recent studies suggest that there is safety in the use of vasoconstrictors at extremities. Thus, we sought to evaluate the effectiveness and safety of vasoconstrictor use combined with local anesthetics in digital nerve block compared to the use of anesthetics without vasoconstrictors, through a systematic review with meta-analysis of randomized clinical trials. Until May 2019 we searched MEDLINE, LILACS, SciELO, ScienceDirect, Scopus, ClinicalTrials.gov, and gray literature databases, without date or language restrictions. The keywords were the following: digital block, vasoconstrictor, and ischemia. We included randomized clinical trials in which there was the use of local anesthetics with associated or not with vasoconstrictors in digital blocks. In the primary variables, the occurrence of ischemic complications and the duration of anesthesia were analysed; in the secondary variables, the need for anesthetic reapplication, bleeding control, and latency were observed. Ten studies were included in this review. The occurrence of ischemia was not observed, regardless of the use of vasoconstrictors or not. The use of vasoconstrictors at a concentration of 1:100,000 or less was associated with longer anesthesia duration (P<0.00001), lower need for anesthetic reapplication (P=0.02), lower need for bleeding control (P=0.00006), and lower latency (P<0.00001). We could conclude that the use of vasoconstrictors associated with local anesthetics in digital block proved to be a safe and effective technique.

Perioperative mortality related to anesthesia within 48 h and up to 30 days following surgery: A retrospective cohort study of 11,562 anesthetic procedures.

STUDY OBJECTIVE: Studying postoperative in-hospital mortality is crucial to the understanding of the perioperative process failures and to the implementation of strategies to improve patient outcomes. We intend to classify the causes of perioperative deaths up to 30 days after procedures requiring anesthesia and to evaluate the risk factors for early (48 h) or late (30 day) mortality. DESIGN: Retrospective cohort study. SETTING: A quaternary University Hospital from South Brazil. PATIENTS: The information related to the perioperative care was collected from surgeries performed between January 2012 and December 2011. INTERVENTIONS: None (observational study). MEASUREMENTS: Three anesthesiologists classified the causes of deaths according to the ANZCA (Australian and New Zealand College of Anesthetists) classification, used in the report of Anesthesia-Related Mortality in Australia since 1985, which defines eight death categories. The risk factors for early or late death were analyzed in a regression model. MAIN RESULTS: 11.562 surgeries were performed, with a mortality incidence of 2.75% within 30 days (319 deaths). Most deaths were inevitable (50.7%), as they were related to advanced illnesses and would occur regardless of anesthetic or surgical procedures. The second most common cause was related to surgical complications (25%). The death rate having anesthesia as a likely contributor was 1.72:10.000 procedures, and as a potential contributor 7.78:10.000. These deaths occurred significantly earlier (<48 h) when compared to deaths from other causes. Transoperative vasopressor, extremes of age and out-of-hour surgery were independent variables associated to early deaths. CONCLUSIONS: The study confirms that postoperative mortality in which anesthesia was involved occurred earlier in the perioperative period. In addition, it was revealed that this involvement of anesthesia as a morbidity contributor shows higher frequency when considering the anesthesiologist perioperative role, and when assessing the mortality in the long term (30 days).

Low-Dose Epinephrine Boluses for Acute Hypotension in the PICU.

OBJECTIVES: To describe the use of low-dose bolus epinephrine in critically ill children during an acute hypotensive episode or prearrest condition. DESIGN: Institutional Review Board approved, single-center, retrospective medical chart review. SETTING: Large medical-surgical PICU within a freestanding, tertiary care children's hospital. PATIENTS: Patients admitted to the PICU between June 1, 2015, and June 1, 2016, who received low-dose (≤ 5 µg/kg) IV bolus epinephrine. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Twenty-four resuscitation episodes (63 doses; 19 patients) were analyzed. Median age and weight of patients were 9 years (interquartile range, 1-15 yr) and 38.5 kg (interquartile range, 12-54.8 kg). Median Pediatric Risk of Mortality III score was 17 (interquartile range, 10-27). Mean epinephrine dose was 1.3 ± 1.1 µg/kg. Median number of doses per patient was two. If more than one dose was provided, median dosing interval was 6.5 minutes. Heart rate and mean arterial blood pressure were compared at the time of epinephrine administration and 1-4 minutes (median = 1 min) following administration. Heart rate changed from 130 ± 41 to 150 ± 33 beats/min (p < 0.05), and mean arterial blood pressure changed from 51 ± 17 to 75 ± 27 mm Hg (p < 0.001). Variability in mean arterial blood pressure response was observed; nonresponders required extracorporeal membrane oxygenation; 66% of doses resulted in up to 100% mean arterial blood pressure increase, and 21% of doses resulted in greater than 100% mean arterial blood pressure increase. Doses below 1 µg/kg were associated with a lower mean arterial blood pressure increase than doses between 1 and 5 µg/kg (mean percent change in mean arterial blood pressure = 6.6% vs 60%, respectively). Children less than or equal to 2 years old had the greatest percentage increase in heart rate and mean arterial blood pressure. CONCLUSIONS: Provision of low-dose bolus epinephrine during periods of acute hypotension can result in a significant increase in mean arterial blood pressure and heart rate. This dosing strategy may provide temporary stabilization while other therapies are added or adjusted, but further research is needed.

Local anaesthetics combined with vasoconstrictors in patients with cardiovascular disease undergoing dental procedures: systematic review and meta-analysis protocol.

INTRODUCTION: The use of vasoconstrictors combined with local anaesthetics (LAs) in dentistry for patients with cardiovascular disease (CVD) is still controversial in the scientific literature. It raises concerns regarding the possibility of transient episodes, triggering negative cardiovascular outcomes. METHOD/DESIGN: Trials eligible for our systematic review will enrol patients with CVD who have undergone dental treatments carried out with the use of LAs by comparing two arms: LAs with vasoconstrictors and LAs without vasoconstrictors. The research will be conducted in the electronic databases, namely Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Healthstar (via Ovid), Cumulative Index to Nursing and Allied Health Literature and Web of Science, from their inception to December 2017, without any restrictions in terms of language and status of publication. A team of reviewers will independently assess titles, abstracts and complete text to determine eligibility. For eligible studies, the same reviewers will perform data extraction and evaluate the risk of bias in the selected articles. The selected outcomes comprise death, mortality by a specific cause, stroke, acute myocardial infarction, hospitalisation, pain, bleeding, arrhythmias, ischaemic episodes, anxiety, adverse effects, changes in blood pressure, changes in heart rate, anxiety and results obtained via oximetry. Whenever possible, we will conduct a meta-analysis to establish the effects of LAs with and without vasoconstrictors in the patients with CVD, and the overall quality of evidence for each outcome will be determined using the Grading of Recommendations Assessment, Development and Evaluation classification system. ETHICS AND DISSEMINATION: Ethics committee approval was not necessary because this is a protocol of systematic review. This systematic review will be submitted for presentation at conferences and for publication in a peer-reviewed journal. Our review will assess the risks of cardiovascular events when using LAs with and without vasoconstrictors in patients with CVD, focusing on important clinical outcomes. PROSPERO REGISTRATION NUMBER: CRD42016045421.

Prenatal phthalate exposure and 8-isoprostane among Mexican-American children with high prevalence of obesity.

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.

The Hydroalcoholic Extract of Leaves of Mandevilla moricandiana Induces NO-Mediated Vascular Relaxation.

Natural products extracted from plants represent a valuable source of new bioactive substances. Many studies describe the potential of plant products for the treatment of cardiovascular diseases. Species of the Mandevilla genus have been studied for their biological activities, mainly as antioxidant, anti-inflammatory, and vasorelaxant. However, the phytochemical and pharmacological profiles of Mandevilla moricandiana have not been investigated yet. The aim of this study was to evaluate the vasodilator effect of the hydroalcoholic extract of the leaves of M. moricandiana, as well as its chemical profile. Chemical analysis and quantification of major compounds were performed by HPLC analysis. Total flavonoid content was quantified based on rutin equivalents, and major compounds were identified based on HPLC-DAD-MS analysis. M. moricandiana leaf extract-induced vasodilation was investigated in rat aortic rings precontracted with phenylephrine. The total flavonoids were quantified as 3.25 ± 0.11 % w/w of the hydroalcoholic leaf extract, and HPLC-DAD-MS allowed for the identification of luteolin and quercetin glycosides. The maximal relaxant effect of the hydroalcoholic leaf extract was 86.07 ± 1.68 % at a concentration of 30 µg/mL (p < 0.05; n = 6). The concentration of hydroalcoholic extract of the leaves of M. moricandiana necessary to reduce phenylephrine-induced contractions of the endothelium-intact aorta by 50 % was 0.82 ± 0.10 µg/mL. M. moricandiana leaf extract-induced vasodilation was abolished in aortas pretreated with NG-nitro-L-arginine methyl ester and 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one. In addition, diphenhydramine partially inhibited the effect of the hydroalcoholic extract of the leaves of M. moricandiana. Thus, M. moricandiana-induced relaxation depends on the endothelium and on the activation of the nitric oxide/cyclic GMP pathway, with the involvement of endothelial histamine H1 receptors. Luteolin and quercetin glycosides seem to contribute to the extract activity.

Déficit de vitamina D en niños ingresados en cuidados intensivos pediátricos / Vitamin D deficiency in children admitted to the paediatric intensive care unit

Introducción: La vitamina D posee múltiples acciones sobre el organismo: es necesaria para la salud ósea, la función cardiovascular y del sistema inmune. En adultos críticos, el déficit de vitamina D (DVD) es frecuente y se ha asociado a sepsis y a desenlaces clínicos desfavorables. Objetivos: Determinar la prevalencia del DVD y establecer su asociación con desenlaces clínicos relevantes en niños ingresados a una Unidad de Cuidados Intensivos Pediátricos (UCIP) en Concepción, región del centro-sur de Chile. Pacientes y método: Estudio de cohorte prospectivo observacional en 90 niños. Los niveles plasmáticos de vitamina D fueron medidos al ingreso en la UCIP. Se analizaron características demográficas, escalas de gravedad (PRISM, PELOD, VIS) y desenlaces clínicos. El déficit de 25OHD se definió como niveles < 20 ng/mL. Se determinó la asociación entre el DVD y desenlaces relevantes mediante el cálculo del riesgo relativo (RR). Resultados: El valor promedio (DE) de la vitamina D en toda la cohorte fue de 22,8 (1,0) ng/mL. La prevalencia del DVD fue del 43,3%. El DVD se asoció significativamente con el uso de fármacos vasoactivos (RR 1,6; IC 95%: 1,2-2,3; p < 0,01), ventilación mecánica (RR 2,2; IC 95%: 1,2-3,9; p < 0,01), shock séptico (RR 1,9; IC 95%: 1,3-2,9; p < 0,001) y necesidad de fluidos de reanimación > 40 ml/kg en las primeras 24 h (RR 1,5; IC 95%: 1,1-2,1; p < 0,05). Conclusiones: En este estudio, el DVD al ingreso en UCIP fue prevalente en pacientes pediátricos críticos y se asoció a desenlaces clínicos adversos. Se requieren más ensayos para determinar si la restauración rápida de los niveles de vitamina D permitiría mejorar los desenlaces clínicos en niños críticamente enfermos.

Introduction: Vitamin D is essential for bone health, as well as for cardiovascular and immune function. In critically ill adults vitamin D deficiency (VDD) is common, and is associated with sepsis and higher critical illness severity. Objectives: To establish the prevalence of VDD and its association with clinically relevant outcomes in children admitted to a Paediatric Intensive Care Unit (PICU) in Concepcion, Chile. Patients and method: Prospective observational cohort study in 90 consecutive children admitted to the PICU in a university general hospital. Blood was collected on admission to PICU and analysed for 25-OH-D levels. Severity of illness and vasopressor use were assessed using PRISM, PELOD, and vasoactive-inotropic score (VIS) score. VDD was defined as a serum 25-OH-D level < 20 ng/ml. Relative risks (RR) were calculated to determine the association between VDD and relevant clinical outcomes. Results: Mean (SD) serum vitamin D (25-OH-D) level in the cohort was 22.8 (1.0) ng/ml. The prevalence of VDD was 43.3%. VDD was associated with vasopressors use (RR 1.6; 95%CI: 1.2-2.3; P<.01), mechanical ventilation (RR 2.2; 95%CI: 1.2-3.9, P<.01), septic shock (RR 1.9; 95%CI: 1.3-2.9, P<.001), and fluid bolus > 40 ml/kg in the first 24 h of admission (RR 1.5; 95%CI: 1.1-2.1, P<.05). Conclusions: In this study, VDD at PICU admission was prevalent in critically ill children and was associated with adverse clinical outcomes. Further studies are needed to assess the potential benefit of optimizing vitamin D status in the PICU.