RESUMO
BACKGROUND AND OBJECTIVE: The pharmacokinetic basis of magnesium sulphate (MgSO4) dosing regimens for preeclampsia (PE) prophylaxis and treatment is not clearly established. The aim of study is to develop a population pharmacokinetic (PK) model of MgSO4 in PE, and to determine key covariates having an effect in MgSO4 pharmacokinetics in preeclampsia (PE) and to determine key covariates having an effect in MgSO4 PK. METHODS: A prospective cohort study was conducted from June 2016 to February 2018 in patients with PE administered MgSO4 as a 4-g bolus followed by continuous infusion at a rate of 1 g/h. Serum magnesium concentrations were obtained before treatment administration and 2, 6, 12, and 18 h after the initial dose. The software Monolix was used to estimate population PK parameters of MgSO4 [clearance (CL), volume of distribution (V), half-life] and to develop a PK model with baseline patient demographic, clinical, and laboratory covariates. RESULTS: The study population consisted of 109 patients. The PK profile of MgSO4 was adequately described by a one-compartment PK model. The model estimate of the population CL was 1.38 L/h; for V, it was 13.3 L; and the baseline magnesium concentration was 0.77 mmol/L (1.87 mg/dL). The baseline body weight and serum creatinine statistically influenced MgSO4 CL and V, respectively. The model was parameterized as CL and V. CONCLUSION: The PK of MgSO4 in pregnant women with PE is significantly affected by creatinine and body weight. Pregnant women with PE and higher body weight have a higher V and, consequently, a lower elimination rate of MgSO4. Pregnant women with PE and a higher serum creatinine value show lower CL and, therefore, lower MgSO4 elimination rate.
Assuntos
Anticonvulsivantes/farmacocinética , Sulfato de Magnésio/farmacocinética , Pré-Eclâmpsia/sangue , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Protocolos Clínicos , Estudos de Coortes , Feminino , Humanos , Infusões Intravenosas , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/sangue , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/prevenção & controle , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Magnesium sulfate is the ideal drug for the prevention and treatment of eclampsia. Nevertheless, the best regimen for protection against eclampsia with minimal side effects remains to be established. This study aimed to compare serum magnesium levels during intravenous infusion of magnesium sulfate at 1âgram/hour versus 2âgrams/hour as a maintenance dose to prevent eclampsia in pregnant and postpartum women with severe preeclampsia. METHODS: A randomized, triple-blind clinical trial was conducted, comparing serum magnesium levels during the intravenous infusion of magnesium sulfate at 1âgram/hour versus 2âgrams/hour as a maintenance dose for the prevention of eclampsia in 62 pregnant and postpartum women with severe preeclampsia, 31 in each group. An intravenous loading dose of 6 grams of magnesium sulfate was administered over 30 minutes in both groups. The patients were then randomized to receive a maintenance dose of either 1 or 2âgrams/hour for 24âhours. Primary outcomes consisted of serum magnesium levels at the following time points: baseline, 30 minutes, every 2 hours until the end of the first 6 hours, and every 6 hours thereafter until the termination of magnesium sulfate infusion. Side effects, maternal complications, and neonatal outcomes were the secondary outcomes. RESULTS: Serum magnesium levels were higher in the 2-gram/hour group, with a statistically significant difference from 2 hours after the beginning of the magnesium sulfate infusion (P <.05). Oliguria was the most common complication recorded in both groups, with no significant difference between the 2 regimens (RR 0.88; 95% CI: 0.49-1.56; P =â.65). No cases of eclampsia occurred. Side effects were more common in the 2-gram/hour group (RR 1.89; 95% CI: 1.04-3.41; P =â.02); however, all were mild. There were no differences between the 2 groups regarding neonatal outcomes, except for admission to neonatal intensive care, which was more frequent in the 1-gram/hour group (25% vs 6.3%; P =â.04). CONCLUSION: Magnesium sulfate therapy at the maintenance dose of 1âgram/hour was just as effective as the 2-gram maintenance dose, with fewer side effects.
Assuntos
Eclampsia/prevenção & controle , Sulfato de Magnésio/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Adulto , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/efeitos adversos , Sulfato de Magnésio/sangue , Período Pós-Parto , Gravidez , Resultado da Gravidez , Adulto JovemRESUMO
OBJECTIVE: To assess the relationship between umbilical cord blood magnesium concentration and level of delivery room resuscitation received by neonates. STUDY DESIGN: This was a secondary analysis of a controlled fetal neuroprotection trial that enrolled women at imminent risk for delivery between 24 and 31 weeks' gestation and randomly allocated them to receive either intravenous magnesium sulfate or placebo. The cohort included 1507 infants with data available on total cord blood Mg concentration and delivery room resuscitation. Multivariate logistic regression was used to estimate the association between cord blood Mg concentration and highest level of delivery room resuscitation, using the following hierarchy: none, oxygen only, bag-mask ventilation with oxygen, intubation, and chest compressions. RESULTS: There was no relationship between cord blood Mg and delivery room resuscitation (OR, 0.92 for each 1.0-mEq/L increase in Mg; 95% CI, 0.83-1.03). Maternal general anesthesia was associated with increased neonatal resuscitation (OR, 2.51; 95% CI, 1.72-3.68). Each 1-week increase in gestational age at birth was associated with decreased neonatal resuscitation (OR, 0.63; 95% CI, 0.60-0.66). CONCLUSION: Cord blood Mg concentration does not correlate with the level of delivery room resuscitation of infants exposed to magnesium sulfate for fetal neuroprotection.
Assuntos
Sangue Fetal/química , Sulfato de Magnésio/sangue , Ressuscitação/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: The purpose of this study was to determine whether magnesium serum concentrations in patients with severe preeclampsia or eclampsia treated with two different magnesium sulfate schemes were different. METHODS: Fourteen patients were randomly assigned in the alternative scheme group and 15 in the Zuspan's group. The difference between the groups was that the intravenously administered maintenance dose was done with 1 g/h by continuous intravenous infusion in the Zuspan's group and 2g in bolus every two hours in the alternative scheme. Blood samples were collected previously to treatment and every 15 minutes during four hours after the beginning of treatment. The primary outcome measure was area under the curve and the t-test was used for statistical analysis with level of statistical significance of 5%. The evaluation of the punctual means at all moments in the alternative group was done with the repeated measures analysis of variance. RESULTS: There was no significant difference in the baseline characteristics between groups. In both schemes, magnesium serum concentration reaches a peak within 15 minutes and a new peak was observed after maintenance dose in the alternative scheme. The area under the curve was significantly lower in the alternative scheme than in the Zuspan's scheme (702.1 +/- 73.5 mg/dL vs 796.1 +/- 94.6 mg/dL). CONCLUSION: The serum magnesium concentration of this randomized clinical trial doesn't support the use of the alternative scheme of magnesium sulfate to prevent or treat eclampsia.
Assuntos
Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/sangue , Pré-Eclâmpsia/tratamento farmacológico , Adulto , Área Sob a Curva , Relação Dose-Resposta a Droga , Esquema de Medicação , Eclampsia/tratamento farmacológico , Eclampsia/prevenção & controle , Feminino , Humanos , Seleção de Pacientes , Gravidez , Resultado do TratamentoRESUMO
OBJECTIVES: To determine whether magnesium sulfate (MgSO(4)) exposure is associated with a reduced risk for neonatal intraventricular hemorrhage (IVH). STUDY DESIGN: In a randomized, controlled trial, women in preterm labor were randomly assigned to receive MgSO(4), "other" tocolytic, or saline control. At delivery, we collected maternal antecubital and umbilical cord blood for determination of serum ionized magnesium levels. Neonatal IVH was diagnosed by cranial ultrasonogram. RESULTS: Among 144 infants, 24 were diagnosed with IVH. Using crude intention-to-treat analysis, we found that 18% (13/74) of survivors exposed after birth to MgSO(4) had IVH compared with 16% (11/70) of babies who were not exposed. Infants who had IVH were more likely to have been delivered by mothers with higher serum ionized magnesium (Mg) levels (0.75 vs 0.56 mmol/L) (P =.01). Using multivariable logistic regression, we confirmed that higher Mg levels are a significant predictor of neonatal IVH (adjusted odds ratio, 15.8; 95% CI, 1.4-175.0) even when adjusted for birth weight, gestational age, antenatal hemorrhage, and neonatal glucocorticoid exposure. CONCLUSIONS: In mothers with preterm labor, our data indicate that antenatal MgSO(4) exposure may be associated with an increased risk for IVH among their newborns.
Assuntos
Hemorragia Cerebral/induzido quimicamente , Sulfato de Magnésio/efeitos adversos , Trabalho de Parto Prematuro/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal , Tocolíticos/efeitos adversos , Adulto , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Sulfato de Magnésio/sangue , Análise Multivariada , Gravidez , Risco , Tocolíticos/sangue , Ultrassonografia , Estados Unidos/epidemiologiaRESUMO
Recently magnesium sulphate (MgSO4) has been used as a bronchodilator in adults with asthma not responding favourably to conventional bronchodilator therapy (CBT). In our institution we treated severe asthmatics with continuous infusion of MgSO4 when everything else failed. However, the optimal dose and frequency to maintain adequate magnesium levels for sustained bronchodilation is not known. The objective of this study was to examine the effect of a continuous infusion of MgSO4 on serum magnesium (Mg) levels, Woods Clinical Asthma Scores (CAS) and side effects in severe asthmatics on standard therapy. Six patients were treated with continuous MgSO4 after they did not respond to CBT. All patients received an initial loading dose of MgSO4 (60-70 mg/kg) during 20 minutes, followed by a continuous infusion of 2-3 g/hr (28-52 mg/kg/hr). Patient data included: Woods Clinical Asthma Score (CAS); Mg levels at baseline (0 min), 40 min and 4 hr after starting the loading dose; electrolytes and ionizing calcium at 4 hr. Patients were monitored continuously for evidence of untoward effect (blood pressure, heart rate and rhythm, deep tendon reflexes). All patients showed sustained clinical improvement. MgS04 may be a beneficial adjunctive therapy for severe asthma. A continuous infusion may maintain adequate levels for sustained bronchodilation with no side effect.(AU)
Assuntos
Adulto , Humanos , Sulfato de Magnésio/uso terapêutico , Broncodilatadores/uso terapêutico , Asma/tratamento farmacológico , Sulfato de Magnésio/sangueRESUMO
It is now well established that the pathophysiology of the malignant hyperthermia (MH) syndrome is related to a malfunction of intracellular calcium homeostasis. Magnesium plays important roles in the basic contractile properties of muscle, and many of its actions are antagonistic to those of calcium. The aim of this study was to determine the effectiveness of magnesium sulphate to prevent the MH episode in susceptible animals and correlate this with its effects on the intracellular free calcium [( Ca2+]i). The experiments were carried out using six control (Yorkshire) and ten MH-susceptible crossbred swine (Poland China X Pietrain). After determination of resting concentrations of [Ca2+]i and [Mg2+]i, each animal was given either two iv bolus doses of 50 mg/kg or one iv bolus of 100 mg/kg of MgSO4. The resting [Ca2+]i and [Mg2+]i were determined by means of ion-selective microelectrodes. The resting [Ca2+]i in normal muscle fibers was 0.11 +/- 0.01 microM (mean +/- SEM), whereas in the MH muscles the resting [Ca2+]i was 0.36 +/- 0.01 microM. In neither group was the resting [Ca2+]i modified by MgSO4. This cumulative dose of MgSO4 (100 mg/kg) was not able to prevent the induction of an MH episode by 2% halothane. Although MgSO4 did not directly decrease [Ca2+]i, it did attenuate the increase in [Ca2+]i associated with the syndrome from 7.29 +/- 0.43 microM in untreated animals to 0.84 +/- 0.03 microM in MgSO4 pretreated swine. In addition, the limb rigidity that accompanies this increase in calcium was prevented by MgSO4 pretreatment. Baseline measurements of [Mg2+]i were not different in control and MH-susceptible muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cálcio/metabolismo , Sulfato de Magnésio/uso terapêutico , Hipertermia Maligna/prevenção & controle , Músculos/efeitos dos fármacos , Animais , Cálcio/análise , Dantroleno/farmacologia , Suscetibilidade a Doenças , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Halotano/farmacologia , Sulfato de Magnésio/sangue , Sulfato de Magnésio/farmacocinética , Hipertermia Maligna/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Microeletrodos , Músculos/metabolismo , Especificidade da Espécie , SuínosRESUMO
En perros anestesiados con pentobarbital sódico se estudió el efecto de la administración parenteral de soluciones de sulfato y cloruro de magnesio sobre algunas variables electrofisiológicas vinculadas a su potencial efecto de la administración parenteral de soluciones de sulfato y cloruro de magnesio sobre algunas variables electrofisiológicas vinculadas a su potencial efecto antiarrítmico. De los resultados obtenidos se puede concluir que tanto el sulfato como el cloruro de magnesio prolongan el período refractario efectivo ventricular (PREV), efecto probablemente relacionado con la prolongación del intervalo QTc. La administración de magnesio prolongó el intervalo AH probablemente por bloquear el canal de Ca++. El cloruro de magnesio no modificó el umbral de fibrilación ventricular (UFV), pero el sultato de magnesio lo hizo descender en forma significativa. Este efecto pudo estar relacionado con la disminución del potasio plasmático inducida por la administración de sulfato de magnesio y a la elevación del magnesio plasmático, porque la administración de sulfato de sodio, que también disminuyó el K+ plasmático, no modificó el UFV. Los efectos antiarrítmicos observados con la aministraciRon de magnesio en pacientes normomagnesémicos podrían ser explicados por una prolongación del PREV. Sin embargo, la disminución del UFV observada en los experimentos con sulfato de magnesio constituye un efecto potencialmente peligroso que merece ser investigado
Assuntos
Cães , Animais , Masculino , Feminino , Cloreto de Magnésio/administração & dosagem , Fibrilação Ventricular/fisiopatologia , Sulfato de Magnésio/administração & dosagem , Cloreto de Magnésio/farmacocinética , Cloreto de Magnésio/sangue , Infusões Intravenosas , Sulfato de Magnésio/sangue , Sulfato de Magnésio/farmacocinéticaRESUMO
En perros anestesiados con pentobarbital sódico se estudió el efecto de la administración parenteral de soluciones de sulfato y cloruro de magnesio sobre algunas variables electrofisiológicas vinculadas a su potencial efecto de la administración parenteral de soluciones de sulfato y cloruro de magnesio sobre algunas variables electrofisiológicas vinculadas a su potencial efecto antiarrítmico. De los resultados obtenidos se puede concluir que tanto el sulfato como el cloruro de magnesio prolongan el período refractario efectivo ventricular (PREV), efecto probablemente relacionado con la prolongación del intervalo QTc. La administración de magnesio prolongó el intervalo AH probablemente por bloquear el canal de Ca++. El cloruro de magnesio no modificó el umbral de fibrilación ventricular (UFV), pero el sultato de magnesio lo hizo descender en forma significativa. Este efecto pudo estar relacionado con la disminución del potasio plasmático inducida por la administración de sulfato de magnesio y a la elevación del magnesio plasmático, porque la administración de sulfato de sodio, que también disminuyó el K+ plasmático, no modificó el UFV. Los efectos antiarrítmicos observados con la aministraciRon de magnesio en pacientes normomagnesémicos podrían ser explicados por una prolongación del PREV. Sin embargo, la disminución del UFV observada en los experimentos con sulfato de magnesio constituye un efecto potencialmente peligroso que merece ser investigado (AU)