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1.
Medicine (Baltimore) ; 98(51): e18311, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860981

RESUMO

BACKGROUND: Studies have shown the efficacy of norepinephrine in the treatment of maternal hypotension during cesarean section by comparing it to treatment with phenylephrine. However, few studies have compared the efficacy of norepinephrine to ephedrine. METHODS: Ninety-seven women undergoing elective cesarean section were administered norepinephrine at 4 µg/minute (group N; n = 48) or ephedrine at 4 mg/minute (group E; n = 49) immediately postspinal anesthesia, with an on-off titration to maintain systolic blood pressure (SBP) at 80% to 120% of baseline. A rescue bolus of 8 µg norepinephrine was given whenever SBP reached the predefined lower limit. Our primary outcome was the incidence of tachycardia. Secondary outcomes included the incidence of bradycardia, hypertension, hypotension, severe hypotension, hypotensive episodes, number of rescue top-ups, hemodynamic performance error including median performance error (MDPE), and median absolute performance error (MDAPE). Neonatal Apgar scores and umbilical arterial (UA) blood gas data were also collected. RESULTS: Women in group N experienced fewer cases of tachycardia (4.2% vs 30.6%, P = .002, odds ratio: 0.11 [95% confidence interval, CI: 0.02-0.47]), a lower standardized heart rate (HR) (70.3 ±â€Š11 vs 75 ±â€Š11, P = .04, difference: 4.7 ±â€Š2.2 [95% CI: 0.24-9.1]), and a lower MDPE for HR (1.3 ±â€Š9.6 vs 8.4 ±â€Š13.5 bpm, P = .003, difference: 3.1 ±â€Š1.8 [95% CI: -0.6-6.7]). In addition, the lowest or the highest HR was lower in group N compared to group E (both P < .05). Meanwhile, the standardized SBP in group N was lower than that in group E (P = .04). For neonates, the UA blood gas showed a higher base excess (BE) and a lower lactate level in group N compared to E (both P < .001). Other hemodynamic variables, maternal, and neonatal outcomes were similar. CONCLUSION: Infusion of 4 µg/minute norepinephrine presented fewer cases of tachycardia, less fluctuation and a lower HR compared to baseline values, as well as a less stressed fetal status compared to ephedrine infusion at 4 mg/minute. In addition, norepinephrine infusion presented a lower standardized SBP compared to ephedrine.


Assuntos
Raquianestesia/métodos , Cesárea/efeitos adversos , Efedrina/uso terapêutico , Hipotensão/prevenção & controle , Norepinefrina/uso terapêutico , Adulto , Raquianestesia/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Cesárea/métodos , Método Duplo-Cego , Efedrina/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipotensão/etiologia , Infusões Intravenosas , Norepinefrina/administração & dosagem , Gravidez
2.
Blood Press Monit ; 24(5): 213-220, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31490245

RESUMO

BACKGROUND: Before arterial cannulation for invasive blood pressure monitoring, clinical decision-making depends on non-invasive blood pressure in critically ill patients. Whether non-invasive blood pressure is comparable to invasive measurement is not clearly elucidated. We address this issue as it relates to the use of norepinephrine in patients with cardiogenic shock. METHODS: We analysed invasive and non-invasive blood pressure in 85 patients admitted to the Coronary-Care Unit for cardiogenic shock. We compared initial blood pressure measurement (just after radial artery cannulation) and blood pressure taken during the first 72 hours after admission. Invasive blood pressure was used as the reference method. RESULTS: Initial invasive mean and systolic arterial pressures were in a good agreement with oscillometric blood pressure; mean differences were -0.4 ± 8.8 and +6.1 ± 14.4 mmHg with correlation coefficients of 0.76 and 0.74. Doses of norepinephrine were significant negative determinants of invasive/oscillometric blood pressure differences. The invasive/oscillometric mean arterial pressures and SBP differences were +0.1 ± 3.4 and 7.6 ± 1.6 mmHg in patients treated with nothing or a maximum norepinephrine dose of 0.6 µg/kg/min. However, treatment with very high doses of norepinephrine was associated with a steep rise in mean arterial pressures and SBP invasive/oscillometric differences (-9.5 ± 3.3 and -8.5 ± 5.2 mmHg). In a total of 967 sets of blood pressure measurements, invasive/oscillometric differences were relatively stable across blood pressure categories, with the exception of measurements assessed after very high norepinephrine doses. CONCLUSIONS: Non-invasive BP is a sufficient substitute for invasive measurement in cardiogenic shock patients, with the exception of those receiving very high doses of norepinephrine.


Assuntos
Determinação da Pressão Arterial/métodos , Pressão Sanguínea/efeitos dos fármacos , Norepinefrina/farmacologia , Choque Cardiogênico/fisiopatologia , Vasoconstritores/farmacologia , Idoso , Idoso de 80 Anos ou mais , Pressão Arterial , Cateterismo , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Norepinefrina/administração & dosagem , Oscilometria/métodos , Estudos Prospectivos , Vasoconstritores/administração & dosagem
5.
Br J Anaesth ; 123(4): 430-438, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31255290

RESUMO

BACKGROUND: Vasopressor agents are used to prevent intraoperative hypotension and ensure adequate perfusion. Vasopressors are usually administered as intermittent boluses or manually adjusted infusions, but this practice requires considerable time and attention. We have developed a closed-loop vasopressor (CLV) controller to correct hypotension more efficiently. Here, we conducted a proof-of-concept study to assess the feasibility and performance of CLV control in surgical patients. METHODS: Twenty patients scheduled for elective surgical procedures were included in this study. The goal of the CLV system was to maintain MAP within 5 mm Hg of the target MAP by automatically adjusting the rate of a norepinephrine infusion using MAP values recorded continuously from an arterial catheter. The primary outcome was the percentage of time that patients were hypotensive, as defined by a MAP of 5 mm Hg below the chosen target. Secondary outcomes included the total dose of norepinephrine, percentage of time with hypertension (MAP>5 mm Hg of the chosen target), raw percentage "time in target" and Varvel performance criteria. RESULTS: The 20 subjects (median age: 64 years [52-71]; male (35%)) underwent elective surgery lasting 154 min [124-233]. CLV control maintained MAP within ±5 mm Hg of the target for 91.6% (85.6-93.3) of the intraoperative period. Subjects were hypotensive for 2.6% of the intraoperative period (range, 0-8.4%). Additional performance criteria for the controller included mean absolute performance error of 2.9 (0.8) and mean predictive error of 0.5 (1.0). No subjects experienced major complications. CONCLUSIONS: In this proof of concept study, CLV control minimised perioperative hypotension in subjects undergoing moderate- or high-risk surgery. Further studies to demonstrate efficacy are warranted. TRIAL REGISTRY NUMBER: NCT03515161 (ClinicalTrials.gov).


Assuntos
Infusões Intravenosas/instrumentação , Norepinefrina/administração & dosagem , Procedimentos Cirúrgicos Operatórios/métodos , Vasoconstritores/efeitos adversos , Idoso , Anestesia , Pressão Sanguínea/efeitos dos fármacos , Procedimentos Cirúrgicos Eletivos , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Resultado do Tratamento , Vasoconstritores/uso terapêutico
6.
Rev Med Chil ; 147(4): 409-415, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344201

RESUMO

BACKGROUND: In critical patients with acute renal failure, intermittent diffusive renal replacement techniques cause hemodynamic problems due to their high depurative efficiency. This situation is avoided using continuous low efficiency therapies, which are expensive, prevent patient mobilization and add hemorrhagic risk due to systemic anticoagulation. Intermittent and prolonged hemodiafiltration (HDF) has the depurative benefits of diffusion, plus the positive attributes of convection in a less expensive therapy. AIM: To report our experience with intermittent and prolonged on-line HDF in critically ill patients. PATIENTS AND METHODS: During 2016, HDF therapies performed on critical patients with indication of renal replacement therapy were characterized. The hemodynamic profile was evaluated (doses of noradrenaline, blood pressure, heart rate and perfusion parameters). RESULTS: Fifty-one therapies were performed in 25 critical patients, aged 58 ± 11 years (28% women), with an APACHE II score of 22.1 ±10. The average time of the therapies was 4.15 hours (range 3-8 hours), the replacement volume was 75 ± 18 mL/kg/h and ultrafiltration rate was 226 ± 207 mL/h. The mean initial, maximum and final noradrenaline doses were 0.07 ± 0.1, 0.13 ±0.18 and 0.09 ±0.16 µg/kg/min respectively. No differences between patients with low, medium and high doses of noradrenaline or dose increases during therapy, were observed. The greatest decrease in mean arterial pressure was 15.3% and the maximum increase in heart rate was 12.8%. Anticoagulation was not required in 88% of therapies. CONCLUSIONS: High-volume intermittent or prolonged HDF is an effective therapy in critical patients, with good hemodynamic tolerability, lower costs and avoidance of systemic anticoagulation risks.


Assuntos
Lesão Renal Aguda/terapia , Estado Terminal/terapia , Hemodiafiltração/métodos , Terapia de Substituição Renal/métodos , APACHE , Idoso , Análise de Variância , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento
7.
Anaesthesia ; 74(7): 850-855, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31044424

RESUMO

Phenylephrine is currently the vasopressor of choice during elective caesarean section, but it can cause reflex bradycardia. Noradrenaline, a potent α-agonist and weak ß-agonist, may be associated with a lower incidence of bradycardia. However, comparative information is limited. This double-blind randomised controlled trial compared the effects of 100 µg phenylephrine and 5 µg noradrenaline administered as boluses for the treatment of postspinal hypotension during elective caesarean section in women with an uncomplicated singleton pregnancy. Hypotension was defined as a decrease of ≥ 20% from baseline systolic arterial pressure, or an absolute value < 100 mmHg. Ninety women were included in the study. The primary outcome was the incidence of maternal bradycardia < 60 beats.min-1 . There was no difference in the incidence of bradycardia (37.8% with phenylephrine vs. 22.2% with noradrenaline; p = 0.167), number of hypotensive episodes, number of boluses required to treat the first hypotensive episode or reactive hypertension. The total number of boluses used was higher in the phenylephrine group (p = 0.01). Maternal heart rate at 1 min after vasopressor administration was non-significantly lower using phenylephrine vs. noradrenaline (p = 0.034, considering p < 0.01 as statistically significant). The umbilical artery pH was higher using phenylephrine than with noradrenaline (p = 0.034). In conclusion, both vasopressors reversed postspinal hypotension without a statistically significant difference in maternal bradycardia. However, in view of the lower umbilical artery pH when using noradrenaline, further research is warranted to study its placental transfer and fetal metabolic effects.


Assuntos
Raquianestesia/efeitos adversos , Cesárea , Hipotensão/tratamento farmacológico , Norepinefrina/uso terapêutico , Fenilefrina/uso terapêutico , Vasoconstritores/uso terapêutico , Adulto , Anestesia Obstétrica/efeitos adversos , Método Duplo-Cego , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Hipotensão/etiologia , Infusões Intravenosas , Norepinefrina/administração & dosagem , Fenilefrina/administração & dosagem , Gravidez , Resultado do Tratamento , Vasoconstritores/administração & dosagem
8.
J Vet Emerg Crit Care (San Antonio) ; 29(3): 326-330, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31044499

RESUMO

OBJECTIVE: To describe the successful management of 2 dogs with septic shock and persistent tachycardia using norepinephrine and esmolol, a short-acting beta receptor antagonist. SERIES SUMMARY: Two cases are reviewed. In the first case, septic shock with ventricular tachycardia was diagnosed in a 4-year-old neutered female Great Dane that underwent jejunoileal resection and anastomosis for a partial mesenteric torsion. The patient's tachyarrhythmias failed to respond to lidocaine, and an esmolol infusion was used for heart rate control. The condition of the dog improved and she was discharged after 4 days of hospitalization. The second case was a 7-year-old neutered female Cavalier King Charles Spaniel with septic peritonitis. Following surgery for intestinal resection and anastomosis, supraventricular tachycardia developed that was not responsive to volume resuscitation and was treated with an esmolol infusion. The condition of the dog improved and she was discharged after 6 days of hospitalization. Both patients were doing well at the time of long-term follow-up. NEW OR UNIQUE INFORMATION PROVIDED: This case series highlights a novel method of managing dogs in septic shock with persistent tachycardia based on recently published data in the human literature. The use of esmolol may be considered in certain veterinary patients with septic shock to improve persistent tachycardia not related to hypovolemia.


Assuntos
Doenças do Cão/tratamento farmacológico , Choque Séptico/veterinária , Taquicardia Supraventricular/veterinária , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Animais , Procedimentos Cirúrgicos do Sistema Digestório/veterinária , Cães , Quimioterapia Combinada/veterinária , Feminino , Norepinefrina/administração & dosagem , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/veterinária , Propanolaminas/administração & dosagem , Choque Séptico/complicações , Choque Séptico/tratamento farmacológico , Taquicardia Supraventricular/complicações , Taquicardia Supraventricular/tratamento farmacológico , Vasoconstritores/administração & dosagem
9.
Int J Clin Pharmacol Ther ; 57(7): 329-333, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31094315

RESUMO

AIM: The aim of this study was to investigate the prescribing patterns of selective serotonin (norepinephrine) reuptake inhibitors (SS(N)RI) in patients treated by general practitioners (GPs) or neurologists/psychiatrists (NPs). MATERIALS AND METHODS: In this retrospective study, we identified patients who received an initial prescription (Rx) of SSRI or SSNRI in 2016 (index date) documented in the IMS® LRx longitudinal pharmacy database. The primary outcome was the proportion of patients who received Rxs from both a GP and an NP, and who switched the prescriber within 1 year after the index date. RESULTS: In total, 345,996 patients (mean age = 55.2 years, 66.4% female) were eligible for analysis, of whom 57.6% received their first Rx from a GP. Over 30% of the patients only received 1 SS(N)RI Rx during the retrospective follow-up period. Of the patients who received at least 2 Rxs, 26.3% received an Rx from both a GP and an NP. This percentage was higher in patients who received their first Rx from an NP (28.4% vs. 24.5%). Multivariate regression analyses showed that younger patients, patients initially treated by an NP, and patients with previous antidepressant prescriptions were more likely to switch prescribers, as were patients who initiated treatment with sertraline or venlafaxine. CONCLUSION: GPs prescribed ~ 60% of the initial SS(N)RI in the year 2016. A fourth of all patients who received at least 2 Rxs switched to another prescriber during follow-up. This switch was associated with age, the type of SS(N)RI prescribed, physician, and previous antidepressant Rxs.
.


Assuntos
Clínicos Gerais , Norepinefrina/administração & dosagem , Padrões de Prática Médica/estatística & dados numéricos , Psiquiatria , Inibidores de Captação de Serotonina/administração & dosagem , Feminino , Seguimentos , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Serotonina
10.
Indian J Pharmacol ; 51(1): 61-71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031469

RESUMO

OBJECTIVES: The objective of the study is to develop an automatic drug infusion control system during cardiovascular surgery. MATERIALS AND METHODS: Based on the clinical drug dosage analysis, the modeling of cardiovascular system with baroreceptor model is mathematically modeled using compartmental approach, considering the relationship between the volume and flow rate of blood during each heartbeat. This model is then combined with drug modeling of noradrenaline and nitroglycerine by deriving the volume and drug mass concentration equations, based on pharmacokinetics and pharmacodynamics of the drugs. The closed-loop patient models are derived from the open-loop data obtained from the physiology-drug model with covariate as age. The proportional-integral controller is designed based on optimal values obtained from bacterial foraging-oriented particle swarm optimization algorithm. The controllers are implemented individually for each control variable such as aortic pressure and cardiac output (CO), irrespective of varying weights based on the relative gain array analysis which depicts the maximum influence of cardiac drugs on control variables. RESULTS: The physiology-drug model output responses are simulated using MATLAB. The controlled responses of aortic pressure and CO with infusion rate of cardiac drugs are obtained. The robustness of the controller is checked by introducing variations in cardiovascular model parameters. The efficiency of the controller during normal and abnormal conditions is compared using time domain analysis. CONCLUSIONS: The controller design was efficient and can be further improved by designing switching-based controllers.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Modelos Cardiovasculares , Nitroglicerina/administração & dosagem , Norepinefrina/administração & dosagem , Pressão Arterial , Débito Cardíaco , Fármacos Cardiovasculares/farmacocinética , Fármacos Cardiovasculares/farmacologia , Humanos , Infusões Intravenosas , Nitroglicerina/farmacocinética , Nitroglicerina/farmacologia , Norepinefrina/farmacocinética , Norepinefrina/farmacologia , Pressorreceptores/fisiologia
11.
Chin Med J (Engl) ; 132(10): 1159-1165, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-30946069

RESUMO

BACKGROUND: New definitions for sepsis and septic shock (Sepsis-3) were published, but the strategy to adjust vasopressors after the initial guidelines is still unclear. We conducted a retrospective observational study to explore dosing strategy of norepinephrine (NE). METHODS: A retrospective observational study in the 15-bed mixed intensive care unit of a tertiary care university hospital. The study was performed on septic shock patients after 30 mL/kg fluid resuscitation and mean arterial pressure (MAP) levels reached >65 mmHg requiring NE. We divided patients into NE dosage increase and decrease groups, and collected hemodynamic and tissue perfusion parameters before (T1) and after (T2) adjusting NE dosage. RESULTS: In both NE increase and decrease groups, central venous pressure (CVP) and pressure difference between usual MAP and MAP (dMAP) at the T1 time point were associated with lactate clearance. In groups LC HM (CVP <10 mmHg, dMAP > 0 mmHg) and HC HM (CVP ≥ 10 mmHg, dMAP > 0 mmHg), decrease in NE dosage decreased lactate level, while in group HC LM (CVP ≥ 10 mmHg, dMAP ≤ 0 mmHg), both increase and decrease in NE dosage led to increase lactate level. CONCLUSIONS: After patients with septic shock (Sepsis-3) resuscitated to reach the initial recovery target goals, combination of CVP and MAP refer to usual levels can help doctors make the next decision to make the correct choice of increase NE dosage or decrease NE dosage.


Assuntos
Pressão Venosa Central/fisiologia , Norepinefrina/administração & dosagem , Norepinefrina/uso terapêutico , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico , Adulto , Idoso , Feminino , Hidratação , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Ressuscitação , Estudos Retrospectivos , Choque Séptico/fisiopatologia , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêutico
12.
Int J Oncol ; 54(5): 1625-1638, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896863

RESUMO

Epidemiological data show that chronic stress has adverse effects on the incidence and progression of cancer. As a critical target organ for stress hormones, the stomach is frequently subjected to stress­related injury. However, few reports regarding the association between stress and gastric cancer (GC) have been published. The present study aimed to investigate the effect of chronic stress on the growth and survival of GC, and the role of the autophagy process. A restraint­stress procedure over 21 days was used to establish a chronic stress mouse model. Subcutaneous xenografts and gastric orthotopic xenografts were established in BALB/c nude mice. Alzet osmotic minipumps containing either PBS or propranolol hydrochloride was inserted on the nape of the neck 7 days prior to the initiation of restraint stress. The presence of autophagosomes and autolysosomes were examined by electron microscopy. The stress hormone norepinephrine significantly enhanced the proliferation of GC cells. By inhibiting adrenoreceptor expression, it was demonstrated that ß2­adrenergic receptor (ADRB2) was the specific ß­adrenergic receptor subtype responsible for catecholamine release. In addition, it was demonstrated that the induction of autophagy was a novel consequence of ß2­adrenergic activation in GC cells. This was demonstrated by the appearance of double­membrane vesicles, punctuate GFP­RFP­microtubule­associated protein 1 light chain 3 distribution in the cytoplasm and a corresponding increase in autophagic flux. Notably, norepinephrine­induced autophagy was shown to have a tumor­promoting role under conditions of chronic stress in vitro and in vivo. It was further demonstrated that, upon activation of cAMP­response element binding protein, chronic stress promoted autophagic flux through the adenosine 5'­monophosphate­activated protein kinase­unc­51 like autophagy activating kinase 1 (AMPK­ULK1) pathway. Tissue microarray analysis revealed a negative correlation between the expression of ADRB2 and autophagic marker p62/sequestosome­1 in GC tumor samples. Additionally, high protein levels of ADRB2 correlated positively with tumor, node, metastasis stage and poor prognosis in patients with GC. These results establish a novel pathway that chronic stress activates tumor­promoting autophagy to accelerate the progression of GC. The present study is the first, to the best of our knowledge, providing preclinical evidence that chronic stress serves a role in the progression of GC.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Norepinefrina/administração & dosagem , Receptores Adrenérgicos beta 2/metabolismo , Neoplasias Gástricas/patologia , Animais , Autofagia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Feminino , Humanos , Masculino , Camundongos , Transplante de Neoplasias , Norepinefrina/farmacologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Análise Serial de Tecidos
13.
Rev Bras Ter Intensiva ; 31(1): 15-20, 2019.
Artigo em Português, Inglês | MEDLINE | ID: mdl-30843950

RESUMO

OBJECTIVE: To describe the incidence of clinical and non-clinical events during intrahospital transport of critically ill patients and to analyze the associated risk factors. METHODS: Cohort study with retrospective data collected from October 2016 to October 2017. All cases of intrahospital transport for diagnostic and therapeutic purposes in a large hospital with six adult intensive care units were analyzed, and the adverse events and related risk factors were evaluated. RESULTS: During the study period, 1,559 intrahospital transports were performed with 1,348 patients, with a mean age of 66 ± 17 years and a mean transport time of 43 ± 34 minutes. During transport, 19.8% of the patients were using vasoactive drugs; 13.7% were under sedation; and 10.6% were under mechanical ventilation. Clinical events occurred in 117 transports (7.5%), and non-clinical events occurred in 125 (8.0%) transports. Communication failures were prevalent; however, the multivariate analysis showed that the use of sedatives, noradrenaline and nitroprusside and a transport time greater than 36.5 minutes were associated with adverse clinical events. The use of dobutamine and a transport time greater than 36.5 minutes were associated with non-clinical events. At the end of transport, 98.1% of the patients presented unchanged clinical conditions compared with baseline. CONCLUSION: Intrahospital transport is related to a high incidence of adverse events, and transport time and the use of sedatives and vasoactive drugs were related to these events.


Assuntos
Estado Terminal , Unidades de Terapia Intensiva , Transporte de Pacientes/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Hospitais , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nitroprussiato/administração & dosagem , Nitroprussiato/efeitos adversos , Norepinefrina/administração & dosagem , Norepinefrina/efeitos adversos , Respiração Artificial/efeitos adversos , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
14.
Med Sci Monit ; 25: 1093-1101, 2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30738019

RESUMO

BACKGROUND This study aimed to compare the efficacy and safety of bolus norepinephrine, phenylephrine, and ephedrine in parturient with preeclampsia who had hypotension during cesarean delivery under spinal anesthesia. MATERIAL AND METHODS One hundred and sixty-six parturient women with preeclampsia who had a baseline systolic blood pressure (SBP) <80% during spinal anesthesia for cesarean section were divided into three treatment groups; bolus norepinephrine 4 µg (group N) (n=56), phenylephrine 50 µg (group P) (n=55), and ephedrine 4 mg (group E) (n=55). Primary outcomes included overall SBP and heart rate (HR) until delivery. Secondary outcomes included the incidence of tachycardia (HR >120 bpm), bradycardia (HR <60 bpm), hypertension (SBP >120% baseline), number of boluses of vasopressor required and episodes of hypotension, maternal side effects, and neonatal outcome. RESULTS Overall HR in group N was significantly increased compared with group P (80.5±12 vs. 76.6±6.9 bpm; P=0.04), and significantly lower compared with group E (80.5±12 vs. 84.9±7.1 bpm; P=0.02). Parturients in group N had fewer episodes of bradycardia compared with group P (3.6% vs. 21.8%; RR=0.26l; 95% CI, 0.07-0.73; P=0.004) and fewer episodes of tachycardia compared with group E (16.1% vs. 36.4%; RR 0.54; 95% CI, 0.29-0.90; P=0.02). CONCLUSIONS A bolus dose of norepinephrine showed similar efficacy to phenylephrine but improved maternal and neonatal safety in parturients with preeclampsia with hypotension during cesarean section under spinal anesthesia.


Assuntos
Hipotensão/tratamento farmacológico , Vasoconstritores/uso terapêutico , Adulto , Raquianestesia , Pressão Sanguínea , Cesárea , China , Efedrina/administração & dosagem , Efedrina/uso terapêutico , Feminino , Frequência Cardíaca , Humanos , Norepinefrina/administração & dosagem , Norepinefrina/uso terapêutico , Parto , Fenilefrina/administração & dosagem , Fenilefrina/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Complicações na Gravidez/tratamento farmacológico , Resultado do Tratamento
15.
Am J Respir Crit Care Med ; 199(9): 1097-1105, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30704260

RESUMO

Rationale: Recent retrospective evidence suggests the efficacy of early norepinephrine administration during resuscitation; however, prospective data to support this assertion are scarce. Objectives: To conduct a phase II trial evaluating the hypothesis that early low-dose norepinephrine in adults with sepsis with hypotension increases shock control by 6 hours compared with standard care. Methods: This single-center, randomized, double-blind, placebo-controlled clinical trial was conducted at Siriraj Hospital, Bangkok, Thailand. The study enrolled 310 adults diagnosed with sepsis with hypotension. The patients were randomly divided into two groups: early norepinephrine (n = 155) and standard treatment (n = 155). The primary outcome was shock control rate (defined as achievement of mean arterial blood pressure ≥65 mm Hg, with urine flow ≥0.5 ml/kg/h for 2 consecutive hours, or decreased serum lactate ≥10% from baseline) by 6 hours after diagnosis. Measurements and Main Results: The patients in both groups were well matched in background characteristics and disease severity. Median time from emergency room arrival to norepinephrine administration was significantly shorter in the early norepinephrine group (93 vs. 192 min; P < 0.001). Shock control rate by 6 hours was significantly higher in the early norepinephrine group (118/155 [76.1%] vs. 75/155 [48.4%]; P < 0.001). The 28-day mortality was not different between groups: 24/155 (15.5%) in the early norepinephrine group versus 34/155 (21.9%) in the standard treatment group (P = 0.15). The early norepinephrine group was associated with lower incidences of cardiogenic pulmonary edema (22/155 [14.4%] vs. 43/155 [27.7%]; P = 0.004) and new-onset arrhythmia (17/155 [11%] vs. 31/155 [20%]; P = 0.03). Conclusions: Early norepinephrine was significantly associated with increased shock control by 6 hours. Further studies are needed before this approach is introduced in clinical resuscitation practice. Clinical trial registered with www.clinicaltrials.gov (NCT01945983) (CENSER trial).


Assuntos
Norepinefrina/uso terapêutico , Ressuscitação/métodos , Choque Séptico/tratamento farmacológico , Vasoconstritores/uso terapêutico , Idoso , Método Duplo-Cego , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/etiologia , Masculino , Pessoa de Meia-Idade , Norepinefrina/administração & dosagem , Choque Séptico/complicações , Choque Séptico/terapia , Vasoconstritores/administração & dosagem
16.
Ann Pharm Fr ; 77(3): 212-221, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30803767

RESUMO

OBJECTIVES: Norepinephrine is usually used in emergency situations such as in intensive care units (ICUs) for the restoration of blood pressure. The objective was to study the stability of highly-concentrated solutions of norepinephrine at 0.50mg/mL and 1.16mg/mL, diluted in glucose 5% (G5%) in polypropylene syringes, protected or not from light, up to 48h. MATERIALS AND METHODS: Chemical stability was analysed by high-performance liquid chromatography coupled to photodiode array detection at each time of the analysis. The method was validated according to the International Conference on Harmonisation Q2(R1). Physical stability was evaluated by visual and subvisual inspection. Three syringes for each condition were prepared. At each time of the analysis, three samples were analysed for each syringe. pH values were evaluated at each moment of the analysis. RESULTS: Solutions of norepinephrine at 0.50 and 1.16mg/mL, diluted in G5%, with or without protection from light, retained more than 95.0% of the initial concentration after a 48-hour storage at 20-25°C. No visual and subvisual modification occured during the stability study. No degradation product appearing during the stressed degradation was observed during the study but an additional peak with a relative retention at 0.66 was observed and constant. This peak was identified as 5-hydroxymethylfurfural, a degradation product of glucose. CONCLUSION: Norepinephrine diluted in G5% at 0.50mg/mL and 1.16mg/mL was physically and chemically stable over a period of 48hours at room temperature. These stability data of highly concentrated solutions provide additional knowledge to assist intensive care services in daily practice.


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Norepinefrina/análise , Vasoconstritores/análise , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Furaldeído/análogos & derivados , Furaldeído/análise , Concentração de Íons de Hidrogênio , Luz , Norepinefrina/administração & dosagem , Polipropilenos , Reprodutibilidade dos Testes , Seringas , Temperatura Ambiente , Vasoconstritores/administração & dosagem
17.
Blood Press Monit ; 24(2): 74-77, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30681421

RESUMO

The aim of our study is to determine whether there is a clinically important difference between the femoral and the radial site of blood pressure measurements, and to identify whether the vasoactive infusion dose influences the femoral-to-radial mean arterial blood pressure (MAP) gradient. We included 71 patients with sepsis and septic shock, with no comorbidities that may influence the hemodynamic parameters. Simultaneous measurements were registered at the femoral and radial arteries. The agreement between the two sites of recording was tested in the no-norepinephrine, low-norepinephrine, and high-norepinephrine groups, as well as for the whole group. Results show that 75.4% of paired recordings have a gradient of at least 5 mmHg between the femoral and radial recordings. For the measurements that have a gradient more than 5 mmHg, norepinephrine infusion dose was not found to be a determining factor. A better level of agreement was found after carrying out a separate Bland-Altman analysis for the femoral-to-radial and radial-to-femoral gradients. Norepinephrine infusion rate was not found to be a determining factor for the femoral-to-radial MAP gradient in septic and septic shock patients. Measurement of MAP at the radial or femoral site is clinically interchangeable for most of these patients.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Artéria Femoral/fisiopatologia , Norepinefrina/administração & dosagem , Artéria Radial/fisiopatologia , Choque Séptico/tratamento farmacológico , Choque Séptico/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Biomater Sci ; 7(4): 1507-1515, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30675877

RESUMO

The clinical applications of particulate drug delivery systems have demonstrated limited treatment outcomes, which is largely attributable to the elimination of such systems by the immune system, especially in the liver. Inspired by the mechanism of nanomaterial clearance by the liver, we designed a new anticancer auxiliary delivery system by introducing norepinephrine loaded poly(acrylic acid) nanogels as angiotonics. The auxilliary system effectively decreased the liver uptake of nanodrugs by increasing the liver blood flow rate. With administration of the as-prepared norepinephrine-loaded poly(acrylic acid) nanogels, the blood perfusion amount increased significantly by 177.0% (i.e. 2.77 times) as observed directly by ultrasonic imaging, indicating an increased blood flow rate in the liver. Since the blood flow rate plays a key role in nanomaterial clearance in the liver, nanodrug clearance should be changed by modulation of the blood flow. Our in vivo experimental results clearly showed the enhancement of nanodrug efficiency with this two-step treatment, with a 52% improvement in plasma drug concentration, obvious drug accumulation in the tumor, and significant antitumor effects. These results indicate that a pre-conditioning strategy involving norepinephrine-loaded poly(acrylic acid) nanogels can serve as an ideal route for reducing nanodrug clearance by the liver.


Assuntos
Resinas Acrílicas/química , Fígado/efeitos dos fármacos , Norepinefrina/farmacocinética , Polietilenoglicóis/química , Polietilenoimina/química , Administração Intravenosa , Animais , Apoptose , Sistemas de Liberação de Medicamentos , Células HEK293 , Células Hep G2 , Humanos , Fígado/irrigação sanguínea , Testes de Função Hepática , Camundongos , Camundongos Endogâmicos ICR , Norepinefrina/administração & dosagem , Norepinefrina/química
19.
Anesthesiology ; 130(1): 55-62, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30335625

RESUMO

BACKGROUND: Norepinephrine has been recently introduced for prophylaxis against postspinal hypotension during cesarean delivery; however, no data are available regarding its optimum dose. The objective of this study is to compare three infusion rates of norepinephrine for prophylaxis against postspinal hypotension during cesarean delivery. METHODS: The authors conducted a double-blinded, randomized, controlled study including full-term pregnant women scheduled for cesarean delivery. Norepinephrine infusion was commenced after subarachnoid block. Patients were randomized into three groups, which received norepinephrine with starting infusion rates of 0.025 µg · kg(-1) · min(-1), 0.050 µg · kg(-1) · min(-1), and 0.075 µg · kg(-1) · min(-1). Infusion was stopped when intraoperative hypertension occurred. The primary outcome was the frequency of postspinal hypotension (defined as decreased systolic blood pressure less than 80% of the baseline reading). The three groups were compared according to the following: systolic blood pressure, heart rate, frequency of intraoperative hypertension, frequency of bradycardia, and neonatal outcomes. RESULTS: Two hundred eighty-four mothers were included in the analysis. The frequency of postspinal hypotension was lower for both the 0.050-µg · kg(-1) · min(-1) dose group (23/93 [24.7%], odds ratio: 0.45 [95% CI: 0.24 to 0.82], P = 0.014) and the 0.075-µg · kg(-1) · min(-1) dose group (25/96 [26.0%], odds ratio: 0.48 [95% CI:0.26 to 0.89], P = 0.022) compared with the 0.025-µg · kg(-1) · min(-1) dose group (40/95 [42.1%]). The two higher-dose groups (the 0.050-µg · kg(-1) · min(-1) group and the 0.075-µg · kg(-1) · min(-1) group) had higher systolic blood pressure and lower heart rate compared with the 0.025 µg · kg(-1) · min(-1) group. The three groups were comparable in the frequency of intraoperative hypertension, incidence of bradycardia, and neonatal outcomes. CONCLUSIONS: Both the 0.050-µg · kg(-1) · min(-1) and 0.075-µg · kg(-1) · min(-1) norepinephrine infusion rates effectively reduced postspinal hypotension during cesarean delivery compared with the 0.025-µg · kg(-1) · min(-1) infusion rate.


Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea , Hipotensão/prevenção & controle , Norepinefrina/uso terapêutico , Agonistas alfa-Adrenérgicos/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Hipotensão/induzido quimicamente , Infusões Intravenosas , Norepinefrina/administração & dosagem , Gravidez , Resultado do Tratamento , Adulto Jovem
20.
Crit Care Med ; 47(2): e89-e95, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30394918

RESUMO

OBJECTIVES: Propofol-based sedation may increase hemodynamic instability by decreasing vascular tone and venous return. Incremental exogenous catecholamines doses may be required to counteract such effects, aggravating the deleterious effects of sympathetic overstimulation. α-2 adrenergic agonists have been reported to decrease norepinephrine requirements in experimental septic shock. The aim of the present study is to test the hypothesis that switching from sedation with propofol to the α-2 agonist dexmedetomidine may decrease norepinephrine doses in septic shock. DESIGN: Prospective open-label crossover study. SETTINGS: University hospital, ICU. PATIENTS: Thirty-eight septic shock patients requiring norepinephrine to maintain adequate mean arterial pressure and needing deep sedation with propofol and remifentanil to maintain a Richmond Agitation-Sedation Scale score between -3 and -4. INTERVENTIONS: An initial set of measurements including hemodynamics, norepinephrine doses, and depth of sedation were obtained during sedation with propofol. Propofol was then replaced by dexmedetomidine and a second set of data was obtained after 4 hours of dexmedetomidine infusion. Sedation was switched back to propofol, and a final set of measurements was obtained after 8 hours. A Richmond Agitation-Sedation Scale score between -3 and -4 was maintained during the study period. MEASUREMENTS AND MAIN RESULTS: Norepinephrine requirements decreased from 0.69 ± 0.72 µg/kg/min before dexmedetomidine to 0.30 ± 0.25 µg/kg/min 4 hours after dexmedetomidine infusion, increasing again to 0.42 ± 0.36 µg/kg/min while on propofol 8 hours after stopping dexmedetomidine (p < 0.005). Dexmedetomidine dosage was 0.7 ± 0.2 µg/kg/hr. Before and after dexmedetomidine infusion, sedative doses remained unchanged (propofol 2.6 ± 1.2 vs 2.6 ± 1.2 mg/kg/hr; p = 0.23 and remifentanil 1.27 ± 0.17 vs 1.27 ± 0.16 µg/kg/hr; p = 0.52, respectively). Richmond Agitation-Sedation Scale was -4 (-4 to -3) before, -4 (-4 to -3) during, and -4 (-4 to -4) after dexmedetomidine (p = 0.07). CONCLUSIONS: For a comparable level of sedation, switching from propofol to dexmedetomidine resulted in a reduction of catecholamine requirements in septic shock patients.


Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Sedação Profunda/métodos , Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Norepinefrina/uso terapêutico , Propofol/uso terapêutico , Choque Séptico/tratamento farmacológico , Equilíbrio Ácido-Base/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/administração & dosagem , Estudos Cross-Over , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/administração & dosagem , Choque Séptico/fisiopatologia
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