Anti-hypertensive therapy for preeclampsia: a network meta-analysis and systematic review.

BACKGROUND: Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality. METHODS: This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31st of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software. RESULTS: We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study. CONCLUSION: According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.

Labetalol Ameliorates Experimental Colitis in Rat Possibly Through its Effect on Proinflammatory Mediators and Oxidative Stress.

BACKGROUND: Members of beta blockers drugs possess significant antioxidant activities. The current research is to assess the effect of the labetalol on acetic acid (AA-induced) colitis in rat model. METHODS: Forty adult Wistar rats were separated into 4 groups, including the negative control group, AA group, AA + sulfasalazine (100 mg/kg/day) group, and AA + labetalol (300 mg/kg/day) group. Colitis was induced in rats by the interrectal installation of 2 mL of 4% (v/v) AA. Sulfasalazine and labetalol were administered orally for 7 days after 2 hours of induction. The following parameters were measured: disease activity index (DAI), histopa-thological changes and colon tissue homogenate concentrations of proinflammatory mediators IL-1ß, adhesion molecules ICAM-1, and oxidative stress marker myeloperoxidase (MPO). RESULTS: The treatment with labetalol significantly reduced DAI and histopathological changes induced by AA. Also, labetalol markedly decreased the concentrations of IL-1ß, ICAM-1, and MPO in colonic tissue that were increased by AA. The effects of labetalol were significantly lower than that produced by sulfasalazine as standard drug. CONCLUSIONS: Labetalol exerts ameliorative effects on disease activity and histopathological features of AA-induced colitis in rats possibly through antioxidant effects and inhibition of inflammatory mediators.

Physiologic Treatment of Severe Hypertension in Pregnancy and Postpartum.

We aimed to evaluate physiologic treatment of severe hypertension. This was a retrospective cohort study of pregnant and postpartum patients with severe hypertension (systolic blood pressure [BP] 160 mm Hg or higher or diastolic BP 110 mm Hg or higher) treated with intravenous labetalol or hydralazine at a single tertiary care center between 2013 and 2018. Patients were classified as having physiologic treatment if they had hyperdynamic physiology (pulse pressure 65 mm Hg or higher) and received labetalol or had vasoconstrictive physiology (diastolic BP 100 mm Hg or higher) and received hydralazine. The primary outcome was number of antihypertensive doses to achieve nonsevere BP. Of 1,120 patients included in the analysis, 653 had physiologic treatment and 467 had nonphysiologic treatment, with 16 (1.4%) excluded for inability to classify physiology. Physiologic treatment was associated with fewer antihypertensive doses (1.4±0.9 doses vs 1.6±1.4 doses; adjusted ß -0.28, 95% CI, -0.42 to -0.14) and lower odds of medication conversion (2.5% vs 4.7%; adjusted odds ratio 0.48, 95% CI, 0.24-0.93) but no difference in time to nonsevere BP (31 minutes [interquartile range 16-66 minutes] vs 34 minutes [interquartile range 15-76 minutes]; adjusted hazard ratio 1.0, 95% CI, 0.9-1.2). Physiologic treatment of severe hypertension warrants further evaluation.

Buffalo yogurt fermented with commercial starter and Lactobacillus plantarum originating from breast milk lowered blood pressure in pregnant hypertensive rats.

Nutritional therapy, which may have advantages over medication, is being investigated as a novel treatment for pregnancy-induced hypertension. Several studies have shown that probiotic yogurt supplementation during pregnancy has beneficial effects on maternal and fetal health. In this study, fermented buffalo milk was produced with yogurt culture and Lactobacillus plantarum B, a probiotic isolated from healthy breast milk with high angiotensin-converting enzyme inhibitory activity. The fermentation conditions under which the angiotensin-converting enzyme (ACE) inhibitory activity reached 84.51% were optimized by the response surface method as follows: 2 × 106 cfu/mL of L. plantarum B, yogurt culture 2.5 × 105 cfu/mL, and 8 h at 37°C. The distribution of ACE inhibitory peptides from fermented buffalo milk and fermented cow milk were further analyzed by liquid chromatography-mass spectrometry. By searching according to the structural features of ACE inhibitory peptides, 29 and 11 peptides containing ACE inhibitory peptide features were found in fermented buffalo milk and fermented cow milk, respectively. To investigate the in vivo antihypertensive activity of fermented buffalo milk, 18 pregnant rats were divided into 3 groups (n = 6 in each group) and administered 10 mL of normal saline, yogurt (20 mg/kg), or labetalol hydrochloride (4 mg/kg) daily from the beginning of pregnancy to parturition. To induce hypertension, methyl nitrosoarginine (125 mg/kg) was injected subcutaneously every day from d 15 of pregnancy to the day of delivery. Blood pressure was not significantly changed in the yogurt and labetalol groups after induction of hypertension and was lower compared with the normal saline group, but there was no difference between the yogurt and labetalol groups. This implied that the buffalo yogurt had a preventive and antihypertensive effect in the pregnancy-induced hypertensive rat model. Further studies to determine the mechanism of action, as well as a randomized control trial, are warranted.

Haemodynamic effects of labetalol in isoflurane-anaesthetized dogs that received dexmedetomidine: A randomized clinical trial.

OBJECTIVE: To test whether labetalol improved cardiovascular function in anaesthetized dogs injected with dexmedetomidine. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A group of 20 healthy client-owned dogs undergoing ovariohysterectomy. METHODS: Each dog received dexmedetomidine (5 µg kg-1) and methadone (0.2 mg kg-1) intramuscularly. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. All dogs were mechanically ventilated, and epidural anaesthesia with lidocaine was performed. Standard anaesthetic monitoring, invasive blood pressure, oesophageal Doppler and near-infrared tissue perfusion/oxygenation were applied. Peak velocity (PV), mean acceleration and stroke distance (SD) from the oesophageal Doppler were recorded. Arterial elastance (Ea) was calculated. Tissue oxygenation (rStO2) was also recorded. Prior to surgery, animals received either 0.1 mg kg-1 of labetalol intravenously (IV) over 60 seconds or the equivalent volume of saline. Data were recorded for 20 minutes. Age, weight and propofol dose were compared with a Wilcoxon rank-sum test. The effects of time, treatment and their interaction with haemodynamic and perfusion variables were analysed with mixed-effect models and Tukey's post hoc tests. RESULTS: Significant effects of the interaction between treatment and time were observed whereby heart rate (HR) was higher in dogs given labetalol (p = 0.01), whereas arterial blood pressure and Ea were lower (p < 0.01). Similarly, PV, SD and rStO2 were higher in the labetalol group, and significant effects were detected for the interaction between treatment and time (p < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Labetalol at a dose of 0.1 mg kg-1 IV in dogs under general anaesthesia and administered a pre-anaesthetic medication of dexmedetomidine produced mild vasodilation (reduction of Ea), resulting in an increase in HR and left ventricular outflow. Although labetalol could be an effective option to achieve haemodynamic optimization after dexmedetomidine-induced vasoconstriction, future studies are needed to assess long-term effects.

Pharmacogenomics of Preeclampsia therapies: Current evidence and future challenges for clinical implementation.

Preeclampsia is a pregnancy-specific disorder, and it is a leading cause of maternal and perinatal morbidity and mortality. The application of pharmacogenetics to antihypertensive agents and dose selection in women with preeclampsia is still in its infancy. No current prescribing guidelines from the clinical pharmacogenetics implementation consortium (CPIC) exist for preeclampsia. Although more studies on pharmacogenomics are underway, there is some evidence for the pharmacogenomics of preeclampsia therapies, considering both the pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs used in preeclampsia. It has been revealed that the CYP2D6*10 variant is significantly higher in women with preeclampsia who are non-responsive to labetalol compared to those who are in the responsive group. Various genetic variants of PD targets, i.e., NOS3, MMP9, MMP2, TIMP1, TIMP3, VEGF, and NAMPT, have been investigated to assess the responsiveness of antihypertensive therapies in preeclampsia management, and they indicated that certain genetic variants of MMP9, TIMP1, and NAMPT are more frequently observed in those who are non-responsive to anti-hypertensive therapies compared to those who are responsive. Further, gene-gene interactions have revealed that NAMPT, TIMP1, and MMP2 genotypes are associated with an increased risk of preeclampsia, and they are more frequently observed in the non-responsive subgroup of women with preeclampsia. The current evidence is not rigorous enough for clinical implementation; however, an institutional or regional-based retrospective analysis of audited data may help close the knowledge gap during the transitional period from a traditional approach (a "one-size-fits-all" strategy) to the pharmacogenomics of preeclampsia therapies.

Hypertensive Emergency: Parenteral Antihypertensives and Population Data.

PURPOSE OF REVIEW: Review parenteral therapeutic choices in treatment of hypertensive crises by mechanism of action and summarize recent literature on the management of hypertensive crises. RECENT FINDINGS: Recent data have documented the safety and efficacy of labetalol and nicardipine in treatment of hypertensive crises as well as characterized the hypertensive emergency population to a much greater extent. Based on recent data, hypertensive emergencies are seen in 0.5% of all emergency room visits. Ischemic stroke and heart failure/pulmonary edema are the most common forms of organ damage seen in hypertensive emergencies. There are many therapeutic choices in treatment of hypertensive crises with varied mechanisms of action. Large randomized, controlled trial evidence is lacking in this therapeutic area; however, recent data have documented the safety and efficacy of labetalol and nicardipine.

Comparison of outcomes following intravenous magnesium compared with intravenous labetalol and oral nifedipine in 355 pregnant Han Chinese women with preeclampsia.

As per the American College of Obstetricians and Gynecologists in 2013, magnesium sulfate is the gold standard for the management of preeclampsia, but it has a short action time that does not provide stable maintenance of blood pressure. Labetalol is currently recommended as first-line treatment by the national UK guidance. This study included 355 pregnant Han Chinese women with preeclampsia and aimed to compare outcomes following intravenous magnesium compared with intravenous labetalol and oral nifedipine. Women received 4 g intravenous magnesium sulfate followed by the maintenance dose of 1 g/h intravenous magnesium sulfate (MS cohort, n = 104) or intravenous labetalol (LB cohort, n = 115), or oral nifedipine (NF cohort, n = 136). Therapy success: systolic blood pressure ~140 mm Hg and diastolic blood pressure ~90 mm Hg, therapy failure: persistent systolic blood pressure ≥ 160 or diastolic blood pressure ≥ 110 mm Hg after maximum dosage of therapy (EL). Women of all cohorts successfully decreased systolic and diastolic blood pressures at EL as compared to them before therapy conditions (P < .001, for all). At EL, systolic and diastolic blood pressures of women of the LB cohort decreased more than those of women of the MS and NF cohorts (P < .05, for all). Therapy was more successful in women of the LB cohort than those of the NF cohort (107 [93%] vs 112 [82%], P = .0132). More numbers of women were reduced blood pressure after 1 day of therapy from the LB cohort than those of the NF (75 [65%] vs 21 [15%]) and MS (75 [65%] vs 35 [34%]) cohorts (P < .0001 for both). Labetalol-induced tachycardia, bradycardia, and intracranial hemorrhage in pregnant women and respiratory distress syndrome and hypoglycemia in neonates. Intravenous labetalol provides proper reduction of blood pressure in Han Chinese women with preeclampsia but has the risk of undesirable maternal and neonatal adverse effects (Level of Evidence: IV; Technical Efficacy: Stage 4).

Safety and efficacy of continuous intravenous labetalol for blood pressure control in neurosurgical patients.

OBJECTIVES: Current evidence supporting the use of continuous intravenous labetalol for blood pressure (BP) control in neurosurgical patients is limited. This study aims to assess the efficacy and safety of labetalol in neurosurgical patients and identify potential contributing factors to these outcomes. METHODS: We retrospectively reviewed the medical records of neurosurgical patients who received continuous labetalol infusion for BP control. Efficacy was assessed based on the time needed to achieve the target BP (systolic BP ≤ 140 mmHg or diastolic BP ≤ 90 mmHg). Safety was assessed according to adverse events that occurred during labetalol administration. Factors associated with efficacy and safety were analyzed using a logistic regression model. RESULTS: Among 79 patients enrolled in this study, 47 (59.49%) achieved the target BP within 1 hour (early response). No factors were significantly associated with an early response. Hypotension was observed in 11 patients (13.9%), and bradycardia was observed in 8 patients (10.1%). Hypotension was significantly associated with patient age and motor impairment, while bradycardia was significantly associated with diabetes mellitus. CONCLUSION: The efficacy and safety profiles of labetalol infusion suggest this treatment as a promising option for BP control in neurosurgical patients.

Further exploration of the collision-induced dissociation of select beta blockers: Acebutolol, atenolol, bisoprolol, carteolol, and labetalol.

Beta blockers are a class of drugs commonly used to treat heart-related diseases; they are also regulated under the World Anti-Doping Agency. Tandem mass spectrometry is often used in the pharmaceutical industry, clinical analysis laboratory, and antidoping laboratory for detection and characterization of drugs and their metabolites. A deeper chemical understanding of dissociation pathways may eventually lead to an improved ability to predict tandem mass spectra of compounds based strictly on their chemical structure (or vice versa), which is especially important for characterization of unknowns such as emerging designer drugs or novel metabolites. In addition to providing insights into dissociation pathways, the use of energy-resolved breakdown curves can produce improved selectivity and lend insights into optimal fragmentation conditions for liquid chromatography-tandem mass spectrometry LC-MS/MS workflows. Here, we perform energy-resolved collision cell and multistage ion trap collision-induced dissociation-mass spectrometry (CID-MS) experiments, along with complementary density functional theory calculations, on five beta blockers (acebutolol, atenolol, bisoprolol, carteolol, and labetalol), to better understand the details of the pathways giving rise to the observed MS/MS patterns. Results from this work are contextualized within previously reported literature on these compounds. New insights into the formation of the characteristic product ion m/z 116 and the pathway leading to characteristic loss of 77 u are highlighted. We also present comparisons of breakdown curves obtained via qToF, quadrupole ion trap, and in-source CID, allowing for differences between the data to be noted and providing a step toward allowing for improved selectivity of breakdown curves to be realized on simple instruments such as single quadrupoles or ion traps.

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA).

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

Evaluation and Management of Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy complicate up to 10% of pregnancies and remain the major cause of maternal and neonatal morbidity and mortality. Hypertensive disorders of pregnancy can be classified into four groups depending on the onset of hypertension and the presence of target organ involvement: chronic hypertension, preeclampsia, gestational hypertension, and superimposed preeclampsia on chronic hypertension. Hypertension during pregnancy is associated with a higher risk of cardiovascular disease and kidney failure. Early diagnosis and proper treatment for pregnant women with hypertension remain a priority since this leads to improved maternal and fetal outcomes. Labetalol, nifedipine, methyldopa, and hydralazine are the preferred medications to treat hypertension during pregnancy. In this comprehensive review, we discuss the diagnostic criteria, evaluation, and management of pregnant women with hypertension.

Comparison of efficacy of intravenous labetalol and intravenous hydralazine for management of pre-eclampsia in pregnant women.

Objectives: To compare the efficacy of intravenous Labetalol and intravenous Hydralazine in reduction of blood pressure in patients with severe pre-eclampsia. Methodology: This comparative study was conducted at the Department of Obstetrics and Gynecology at Ziauddin University Hospital, Karachi from1st June 2019 to 30th June 2020. Total 208 pregnant women having severe pre-eclampsia (systolic pressure ≥160 mmHg and diastolic pressure ≥110mmHg) were included in study. Group A received I/V Labetalol. Group B received I/V Hydralazine. Efficacy of drugs was observed by reduction in blood pressure and the number of doses administered. Data was analysed using SPSS version 26. Results: Systolic blood pressure reduction in Labetalol group was significantly lower than in hydralazine group (105.5 ±11.3 vs. 115.8 ±17.1, p≤ 0.001). Diastolic blood pressure reduction was also lower in labetalol group than in hydralazine group (p= 0.03). Number of dosage of drugs in Group A (Labetalol) was 3.2 ±1.2 vs. Group B (Hydralazine) was 4.4±1.4, p =0.006). Conclusion: The results of this study show that Labetalol is more effective as compared to Hydralazine in terms of reducing the systolic and diastolic blood pressure and number of doses (Drugs) for in patients with severe preeclampsia.

Oral nifedipine may be a preferential option for treating acute severe hypertension during pregnancy: a meta-analysis.

AIM: To compare oral nifedipine and intravenous labetalol in the treatment of acute severe hypertension in pregnancy (SHP). METHODS: The primary outcomes were the required time to achieve target blood pressure (RTATBP), systolic blood pressure (SBP) and diastolic BP (DBP) after treatment, secondary outcomes were the number of doses (NoD) and adverse events (AEs). RESULTS: There was no difference between oral nifedipine and intravenous labetalol in SBP, DBP, and AE. However, oral nifedipine provided less RTATBP and NoD. CONCLUSION: Oral nifedipine was associated with less RTATBP and NoD and otherwise did not differ from intravenous labetalol.

Oral nifedipine versus intravenous labetalol for hypertensive emergencies during pregnancy: a systematic review and meta-analysis.

Aim: The optimal drug management strategy for severe hypertension during pregnancy remains inconclusive. Some randomized controlled trials found that oral nifedipine was more effective than intravenous labetalol in hypertensive emergencies during pregnancy, while others found otherwise. As a result, we conducted a meta-analysis to assess the effectiveness of oral nifedipine versus intravenous labetalol for hypertensive emergencies during pregnancy.Methods: We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials that compared oral nifedipine versus IV labetalol in hypertensive emergencies during pregnancy.Results: 12 RCTs enrolling 1151 participants (573 in the labetalol group and 578 in the nifedipine group) were included in the meta-analysis. Patients who received oral nifedipine reached their target blood pressure more rapidly than those who received intravenous labetalol (MD 7.64, 95%CI 4.08-11.20, p < .0001). The nifedipine group required fewer doses to achieve the target blood pressure (MD 0.62, 95%CI 0.36 to 0.88, p < .00001). There were no meaningful differences on the maternal complications between the two groups, mainly including eclampsia (OR 1.51; 95% CI, 0.75-3.05; p = .25), headache (OR 0.86; 95% CI, 0.52-1.44; p = .57), nausea/vomiting (OR 1.50; 95% CI, 0.76-2.93; p = .24), hypotension (OR 0.49; 95% CI, 0.12-1.99; p = .32), dizziness (OR 2.01; 95% CI, 0.77-5.25; p = .16), HELLP (OR 0.27; 95% CI, 0.05-1.64; p = .16), palpitations (OR 0.63; 95% CI, 0.32-1.27; p = .20), flushing (OR 0.77; 95%CI, 0.18-3.22; p = .72). There were no significant difference in the neonatal complications, including NICU admission (OR 1.24; 95% CI, 0.87-1.77; p = .23), 5 min Apgar score < 7 (OR 1.07; 95% CI, 0.82-1.39; p = .63), neonatal deaths (OR 1.08; 95%CI, 0.66-1.76; p = .77), FHR abnormality (OR 0.94; 95%CI, 0.47-1.88; p = .86).Conclusion: In conclusion, oral nifedipine could achieve target blood pressure more rapidly and required fewer doses than intravenous labetalol in the management of hypertensive emergencies during pregnancy.

Does Labetalol Trigger False Positive Drug Testing Results?

OBJECTIVES: Labetalol, an α- and ß-adrenergic antagonist used to treat hypertension in pregnancy has been blamed for causing false-positive amphetamine and methamphetamine results. In this study, we tested 3 concentrations of labetalol prepared with 4 specimen types (urine, plasma, meconium, and umbilical cord tissue), for amphetamine, methamphetamine, and several other drugs with screen and confirmation tests. METHODS: Residual drug-free specimens were pooled. Labetalol hydrochloride dissolved in methanol was used to prepare spikes in triplicate per specimen type (2.7, 50, and 100 µM), which were tested with 41 previously validated drug tests performed by immunoassay or liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: Labetalol triggered false-positive amphetamine and methamphetamine results by immunoassay in meconium but did not trigger positive results for any of the targeted drugs or drug metabolites tested by LC-MS/MS. No positive results were generated by any immunoassay or LC-MS/MS test included in the study, when challenged with high concentrations of labetalol in urine, plasma, or umbilical cord tissue. CONCLUSIONS: In summary, false-positive results can be generated by labetalol when tested by immunoassay, but false-positive results are not expected when testing is performed by highly specific analytical approaches such as LC-MS/MS.

Hypertension in Pregnancy: A Diagnostic and Therapeutic Overview.

Hypertensive disorders in pregnancy are associated with increased risk of maternal, fetal, and neonatal morbidity and mortality. It is important to distinguish between pre-existing (chronic) hypertension and gestational hypertension, developing after 20 weeks of gestation and usually resolving within 6 weeks postpartum. There is a consensus that systolic blood pressure ≥ 170 or diastolic blood pressure ≥ 110 mmHg is an emergency and hospitalization is indicated. The selection of the antihypertensive drug and its route of administration depend on the expected time of delivery. The current European guidelines recommend initiating drug treatment in pregnant women with persistent elevation of blood pressure ≥ 150/95 mmHg and at values > 140/90 mmHg in women with gestational hypertension (with or without proteinuria), with pre-existing hypertension with the superimposition of gestational hypertension, and with hypertension with subclinical organ damage or symptoms at any time during pregnancy. Methyldopa, labetalol, and calcium antagonists (the most data are available for nifedipine) are the drugs of choice. The results of the CHIPS and CHAP studies are likely to reduce the threshold for initiating treatment. Women with a history of hypertensive disorders in pregnancy, particularly those with pre-eclampsia, are at high risk of developing cardiovascular disease later in life. Obstetric history should become a part of the cardiovascular risk assessment in women.

Precipitation of sugammadex with nicardipine and labetalol: A laboratory research.

There is a paucity of clinical data about whether sugammadex forms precipitates with other medications. This laboratory experimental study was performed to determine the drugs that produce precipitates with sugammadex. Samples of 1 ml of sugammadex were prepared in transparent cylinders, to which 1 ml of test drugs (rocuronium, neostigmine, glycopyrrolate, atropine, nitroglycerin, dobutamine, dopamine, epinephrine, vasopressin, norepinephrine, phenylephrine, ephedrine, esmolol, nicardipine, and labetalol) was added. The precipitation reaction was observed visually and via light microscope. The pH of each drugs before and after mixing with sugammadex was measured. White crystals were formed when sugammadex was mixed with nicardipine or labetalol. Sugammadex formed precipitate when mixed with nicardipine or labetalol. Sufficient fluid flushing is required between injections of each drug to prevent these reactions.