Intravenous Nicardipine Research Articles

Management of preoperative hypertension and anxiety based on early monitoring of pulse rate before cataract surgery.

Few studies have addressed the clinical impact of fluctuation in pulse rate before cataract surgery. This study aimed to determine the effectiveness of prior pulse monitoring and intervention to prevent blood pressure changes in patients undergoing cataract surgery under local anesthesia. Retrospective study METHODS: Patients who underwent cataract surgery under local anesthesia were included. In the pulse rate (PR) group, intervention was performed on the basis of early monitoring of blood pressure and PR changes. In the conventional group, blood pressure was managed on the basis of blood pressure alone. Systolic blood pressure, diastolic blood pressure, intraoperative nicardipine use, and physician consultation time were retrospectively compared between the groups. The study included 684 eyes from 684 patients aged 73.5 ± 9.5 years (PR group: 297 eyes, conventional group: 387 eyes). No intergroup differences were found in systolic blood pressure or pulse and heart rates; however, diastolic blood pressure was significantly lower in the PR group than in the conventional group at both the beginning and the end of surgery (P <.001 and P = .0028, respectively). Intravenous nicardipine administration in the operating room was significantly less frequent in the PR group (P = .041), and physician consultation time after entering the operating room and at the beginning of surgery was significantly shorter in the PR group (both P <.001). Early monitoring of PR with blood pressure and intervention were effective for preventing preoperative hypertension.

Optimal treatment for women with acute hypertension in pregnancy; a randomized trial comparing intravenous labetalol versus nicardipine

ObjectivesBlood pressure control in severe hypertension of pregnancy is crucial for mother and neonate. In absence of evidence, guidelines recommend either intravenous labetalol or nicardipine. We compared the effectiveness and safety of these two drugs in women with severe hypertension in pregnancy. Study designWe performed an open label randomized controlled trial. Women with a singleton pregnancy complicated by severe hypertension (systolic ≥ 160 mmHg and/or diastolic ≥ 110 mmHg) requiring intravenous antihypertensive treatment were randomized to intravenous labetalol or intravenous nicardipine. The primary outcome was a composite adverse neonatal outcome defined as severe Respiratory Distress Syndrome (RDS), Broncho Pulmonary Dysplasia (BPD), Intraventricular Hemorrhage (IVH) IIB or worse, Necrotizing Enterocolitis (NEC), or perinatal death defined as fetal death or neonatal death before discharge from the neonatal intensive care unit (NICU).Based on a power analysis, we estimated that 472 women (236 per group) needed to be included to detect a difference of 15% in the primary outcome with 90% power. The study was halted prematurely at 30 inclusions because of slow recruitment and trial fatigue. ResultsBetween August 2018 and April 2022, we randomized 30 women of which 16 were allocated to intravenous nicardipine and 14 to intravenous labetalol. The composite adverse neonatal outcome was not significantly different between the two groups (25 % versus 43 % OR 0.28 (95 % CI 0.05–1.43), p = 0.12)). Respiratory distress syndrome occurred more often in the labetalol group than in the nicardipine group (42.9 % versus 12.5 %). Neonatal hypoglycemia occurred more often in the nicardipine group than in the labetalol group (31 % versus 7 %). Time until blood pressure control was faster in women treated with nicardipine than in women treated with labetalol (45 (15–150 min vs. 120 (60–127,5) min). ConclusionIn our prematurely halted small RCT, we were unable to provide evidence for the optimal choice of treatment for severe hypertension to improve neonatal outcome and/or to obtain faster blood pressure control. Differences in Respiratory distress syndrome and neonatal hypoglycemia between the groups might be the result of coincidental finding due to the small groups included in the study. A larger randomized trial would be needed to determine the safest and most efficacious (intravenous) therapy for severe hypertension in pregnancy. This study emphasizes the challenges of conducting a RCT for the optimal treatment for these women.

Effects of intravenous nicardipine followed by oral labetalol in combination with nifedipine controlled-release tablet on severe peripartum hypertension.

To investigate the effects of intravenous nicardipine as initial therapy and oral labetalol combined with nifedipine controlled-release tablet as subsequent treatment of severe peripartum hypertension. Intravenous nicardipine was delivered as the initial treatment, after the target blood pressure (BP) had been achieved, oral labetalol was used to maintain the target BP. If oral labetalol failed to maintain the target BP, oral labetalol combined with nifedipine controlled-release tablet was used. A total number of 131 patients were enrolled. The target BP (BP < 140/90 mmHg) was achieved in all patients within 60 minutes by intravenous nicardipine. After receiving labetalol orally, the target BP was maintained in nine patients. However, in 104 patients, we had to combine oral labetalol and nifedipine controlled-release tablet due to re-elevation of their systolic BP to 140-159 mmHg. In 18 patients, we restarted intravenous nicardipine because their systolic BP re-elevated above 160 mm Hg. Among the 104 patients who received oral labetalol and nifedipine controlled-release tablet, the target BP was achieved and maintained in 96 patients, and eight patients had to restart nicardipine. Of the total number of 26 patients in whom intravenous nicardipine was resumed, the target BP was successfully maintained in 22 patients with oral labetalol combined with nifedipine controlled-release tablet. Intravenous nicardipine rapidly and safely lowered severe peripartum hypertension. As subsequent therapy, oral labetalol combined with nifedipine controlled-release tablet protocol may be applied to effectively maintain a target BP.

Utility of nicardipine in the management of hypertensive crises in adults with reduced ejection fractions

BackgroundNicardipine is commonly used in the management of hypertensive crises, except those involving cardiac contractility defects despite its ability to reduce afterload and pulmonary congestion. Consequently, there is limited literature evaluating nicardipine's role for this indication. The purpose of this study was to evaluate the efficacy and safety of nicardipine in adults with reduced ejection fractions presenting with acute heart failure with hypertension (AHF-H). MethodsThis was a retrospective study conducted at an academic Level 1 trauma center with an annual Emergency Department (ED) volume surpassing 100,000. The purpose of this study was to determine the efficacy and safety of nicardipine in adults with reduced ejection fractions presenting to the ED with AHF-H. Efficacy was determined by achievement of the physician prescribed blood pressure target range. The primary safety endpoints included the number of individuals who experienced bradycardia (< 60 beats per minute, bpm) or hypotension (systolic blood pressure, SBP, < 90 mmHg) while receiving nicardipine and for up to 15 min after its discontinuation. Patients were included if they were ≥ 18 years of age, received a continuous intravenous nicardipine infusion within six hours of presenting to the ED, and had an ejection fraction ≤ 40% per an echocardiogram obtained within three months of the study visit. Pregnant and incarcerated patients were excluded. ResultsOf the 500 patient charts reviewed, 38 met inclusion criteria. The median (interquartile, IQR) ejection fraction and brain natriuretic peptide (BNP) were 35% (25–40) and 731 pg/nL (418–3277), respectively. The median baseline heart rate and SBP were 90 bpm and 193 mmHg, respectively. The median physician specified SBP goal was 160 mmHg and all patients met this endpoint in a median time of 18 min. One (2.6%) patient in the total population developed both hypotension and bradycardia. This patient had an ejection fraction of 20%, was intubated, and received nicardipine in addition to esmolol for an aortic dissection without experiencing an adverse event until 30 min after dexmedetomidine was initiated. ConclusionIn this non-interventional study evaluating the use of nicardipine in patients with reduced ejection fractions presenting to the ED with AHF-H, nicardipine was found to be safe and effective. To our knowledge this is the largest study to date evaluating nicardipine in this patient population and positively contributes to the existing literature.

Hypoxia Associated With Dihydropyridine Calcium Channel Inhibitors: A Pharmacovigilance Study in VigiBase.

Due to their negative effects on hypoxic pulmonary vasoconstriction, dihydropyridine calcium channel inhibitors (DCCIs) can lead to hypoxia in patients with a pulmonary shunt. To date, only preclinical studies and case reports have focused on this potential adverse drug reaction. We aimed to assess the reporting association between DCCIs and hypoxia using the World Health Organization pharmacovigilance database (VigiBase). We performed a disproportionality analysis to evaluate the strength of the reporting association between i.v. clevidipine and nicardipine, thought to be a surrogate of patients in the intensive care unit, and hypoxia. The information component and the lower end of its 95% credibility interval were used to evaluate disproportionality. A description of the cases was made. Secondary outcomes included the association between all DCCIs and hypoxia compared with other treatments with similar indications, urapidil and labetalol, regardless of the route of administration. Association between oral nicardipine and hypoxia was also searched. A statistically significant signal of hypoxia was found for intravenous clevidipine and nicardipine. The time to onset was reported with a median of 2 days (interquartile range 1.5-4.5). Four dechallenges were performed with intravenous nicardipine, leading to the resolution of the symptoms. Regardless of the route of administration, a signal of hypoxia was also found for nimodipine but not for other drugs, including comparators. For nicardipine no signal of hypoxia was found with the oral route of administration. Our pharmacovigilance database analysis showed a significant association between the use of intravenous DCCIs and hypoxia.

Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia.

The treatment of preeclampsia is delivering women and extracting the placenta, but the Chinese Society of Obstetrics and Gynecology guidelines do not recommend the delivery of babies without severe features. The objectives of the study were to compare the effectiveness and safety of nifedipine and phytosterol in combination with nicardipine for the management of severe preeclampsia. Women (19-32 years; gestation age ≥ 30 weeks) with the complication of severe preeclampsia have received 10 mg of oral nifedipine (pregnant women received 10 mg of oralnifedipine, n = 112) or 1 mg/h intravenous nicardipine (pregnant women received 1 mg/h intravenous nicardipine (ND cohort), n = 115) or oral 10 mg nifedipine and 500 mg phytosterol (pregnant women received oral 10 mg nifedipine and 500 mg phytosterol (np cohort), n = 111) until 150/100 mmHg blood pressure was achieved. The time required to achieve the desired blood pressure control was 13 minutes shorter in the NP cohort compared to the NF (p < 0.0001, t = 11.605), and 3 minutes shorter compared to the ND (p < 0.0001, t = 2.79) cohorts. Stillbirths were reported in 14 (13%), 28 (24%), and 10 (9%) infants, and 13 (12%), 26 (23%), and 10 (9%) infants died from the NF, ND, and NP cohorts, respectively. The undesirable tocolytic effect was reported in 17 (15%) women of the ND cohort. Phytosterol with nifedipine has a synergistic or additive effect on the management of preeclampsia with fewer adverse outcomes.

Changes in Mean Arterial and Blood Pressure in Using Nicardipine in Hypertensive Crisis Patients at the Hajj General Hospital Surabaya from August to December 2021

Hypertension crisis is one of the most common disease problems; it will cause complications and death. Therapeutic management guidelines that the calcium channel blocker group, one of which is nicardipine, can increase the achievement of goals in mean arterial pressure (MAP) in preventing the progression of organ damage. This study aimed to evaluate the use of nicardipine therapy on the MAP and blood pressure (BP) in patients with hypertension crisis. The research design was cross-sectional with statistical analysis—retrospective data collection at Hajj General Hospital Surabaya for August to December 2021. The number of samples in this study matched the inclusion criteria; 20 patients were obtained, 16 with a diagnosis of hypertension emergency, and four with hypertension urgency who received single or combined intravenous nicardipine therapy &lt;0.005 with an average BP decrease of pre 20.375±31.492/103.50±10.400 mmHg and post 121.34±14.364/81.80±11.186 so that intravenous nicardipine therapy was significant in reducing systolic and diastolic BP. In the profile of the MAP value statistically using the paired T-test, it was found that the P-value was 0.000 &lt; 0.005 with a decrease in the MAP pre-value of 135.028±13.8857 mmHg and post 93.650±8.9499 mmHg, showing a reduction in MAP as expected. In conclusion, using nicardipine intravenously at a 5 mg/hour dose has shown an optimal decrease in BP and MAP in hypertensive emergency and urgency patients.

Abstract TP122: Systolic Blood Pressure Variability Increases During The Initial 24 Hours After Intravenous Nicardipine Administration Among Patients With Primary Intracerebral Hemorrhage

Background: Systolic blood pressure variability (SBPV) has been associated with poor outcomes among patients with intracerebral hemorrhage (ICH). Intravenous nicardipine (IVN) is frequently used for blood pressure management among hospitalized ICH patients, however SBPV in response to IVN has not been characterized. Methods: Data for primary ICH patients who received IVN were retrieved from a stroke-specific bioinformatics pipeline. SBPV was quantified as the coefficient of variation (CV) of cuff-measured systolic blood pressure, and CV was calculated over the time periods 0-24 hrs prior to (Pre24), 0-24 hrs after (Post24), and 24-48 hrs after (Post48) initial IVN administration. Group differences were assessed using Friedman’s Test and Bonferroni-corrected Wilcoxon Signed-rank tests. Contributions of SBPV at each timepoint to poor in-hospital mortality or discharge to hospice (poor outcome) were assessed in separate multivariable logistic regression models adjusted for patient characteristics. Adjusted Odds ratios (aOR) and 95% confidence intervals (CI) are reported. Results: Data included 370 ICH patients with a median [interquartile range] age of 65 [54 - 76]. Patients included were 46.0% female, 41.1% Non-Hispanic White, 25.1% Non-Hispanic Black, 23.8% Hispanic, 8.1% Asian, and 1.9% other. Patients had a median CV of 9.2 [6.1-13.6] in the Pre24 period, 11.6 [9.46 - 13.9] in Post24, and 9.5 [7.6 - 12.1] in Post48. SPBV showed significant differences across timepoints (p=0.000), with Post24 showing elevated SBPV (vs. Pre24 (p=0.000) or Post48 (p=0.000), Figure 1A, B). In multivariable modelling, patients in the highest quartile of SPBV during the Post24 period showed increased risk of poor outcome: aOR (CI) 2.91 (1.06-8.01), Figure 1C. Conclusions: SBPV increases over the first 24 hours of IVN administration and patients with higher SPBV during this time are at higher risk for in-hospital mortality. SPBV management protocols need to be evaluated.

S-06-3: EMERGENT BLOOD PRESSURE LOWERING WITH INTRAVENOUS NICARDIPINE FOR JAPANESE PATIENTS WITH ACUTE INTRACEREBRAL HEMORRHAGE: AN INDIVIDUAL PARTICIPANT DATA ANALYSIS

Objective: Intensive lowering of elevated blood pressure is one of the few promising therapies for acute intracerebral hemorrhage. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine for Japanese patients with acute intracerebral hemorrhage on clinical outcomes were determined. Design and method: A systematic review and individual participant data analysis of articles before October 1, 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving adults developing hyperacute intracerebral hemorrhage who were treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4–6, and hematoma expansion, defined as an increase 6 mL or more from baseline to 24-h computed tomography. In this study, data on Japanese patients were extracted. The study is registered with PROSPERO (CRD42020213857). Results: Three studies, ATACH-1, ATACH-2, and SAMURAI-ICH, met the eligibility criteria. Of 1,271 patients enrolled, 500 were registered from Japan, and all of these were Japanese. A patient with available data on the hourly blood pressures only for &lt; 4 timepoints was excluded, and the other 449 patients (age 64.9 ± 11.8 years, 183 women, initial BP 203.5v± 18.3 / 109.1 ± 17.2 mmHg) were studied. Death or disability occurred in 35.6%, and hematoma expansion occurred in 15.6%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio 1.26, 95% confidence interval 1.04–1.53 per 10 mmHg) and hematoma expansion (1.47, 1.17–1.85). These odds ratios were relatively high as compared to the reported ones for global patients of this individual participant data analysis [1.12 (95% confidence interval 1.00–1.26) and 1.16 (1.02–1.32), respectively] (Toyoda K, et al: Int J Stroke 2021). Conclusions: Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h was associated with lower risks of hematoma expansion and 90-day death or disability in Japanese patients with hyperacute intracerebral hemorrhage. The impact of systolic blood pressure lowering on better outcome seemed to be stronger in Japanese patients than the global ones.

PS-R01-7: A CASE REPORT OF ACCELERATED-MALIGNANT HYPERTENSION SUCCESSFULLY TREATED WITH SACUBITRIL/VALSARTAN

Angiotensin receptor-neprilysin inhibitor (ARNI) is an emerging therapeutic strategy for cardiorenal syndrome. Although the treatment with ARNI for hypertension is covered by governmental insurance systems in Japan, a putative position of ARNI in clinical hypertension guidelines is yet to be determined. However, clinical and experimental evidence is now accumulating concerning the therapeutic effects of ARNI for hypertension, in addition to heart failure, in Japan. Here we would like to present a case in which treatment with ARNI for hypertension was effective to beneficially control cardiorenal syndrome as well as hypertension. A 51-years-old man with a history of hypertension since 35 years-old experienced shortness of breath on exertion and on supine position visited Yokohama City University Hospital. Severely elevated blood pressure (234/165 mmHg) with hypertensive retinopathy (Keith-Wagner IIb, Scheie S2H3), as well as cardiorenal dysfunction (LVEF 39% on UCG, eGFR 25.4 mL/min/1.73m2, UPCR 0.56 g/gCr), were noted, and he was admitted to the hospital due to accelerated-malignant hypertension. On admission, the patient was administered with intravenous nicardipine to achieve blood pressure level around 160/110 mmHg, and then treated with oral nifedipine (40–80 mg daily) with tapering of intravenous nicardipine administration. After treatment transition to single oral nifedipine therapy (80 mg daily), his blood pressure was still around160/110 mmHg. Thus, treatment with ARNI (sacubitril/valsartan) was initiated with a starting dose of 50 mg daily on Day 9. On Day 10, his blood pressure was improved to around 130/90 mmHg without evident worsening of kidney function or elevation of serum potassium level. The patient was successfully treated with appropriate control of blood pressure without initiation of dialysis. This case suggests that ARNI is an interesting therapeutic strategy to treat cardiorenal syndrome with severe hypertension.

PS-C26-6: HYPERTENSION DUE TO HYDRONEPHROSIS SECONDARY TO IGG4-RELATED DISEASE

Background: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that is capable of affecting multiple organs. It can present as an inflammatory pseudotumor in various organs. Patients may present with normo- or hypertension (HT) and urinary tract obstruction (UTO). Hydronephrosis (HN) leads to HT by overloading vessels or activating the renin-angiotensin system. Case presentation: A 53-year-old man presented with a two week history of abdominal pain. At admission, his blood pressure (BP) was 208/112 mmHg. His physical examination was otherwise unremarkable. Laboratory data and imaging revealed post-renal azotemia. HN was identified due to a mass around the aorta causing bilateral ureteric compression. The right ureter was considered to be more recently compressed because the left kidney cortex was more extensively thinned compared to the right kidney, respectively. Insertion of a double J stent in the right ureter led to improve urinary output with an attendant reduction of weight of 7 kg. Renal function also improved substantially (serum creatinine 5.66 mg/dL at admission; 1.34 mg/dL post-stent insertion). Initial treatment included intravenous nicardipine, followed oral nifedipine and telmisartan. With the above interventions, HT normalized to 132/71 mmHg in nine days. Finally, only telmisartan was required to maintain normal BP upon discharge. Biopsies of a salivary gland, the lip, and a cervical lymph node were non-diagnostic. The abdominal mass was not biopsied. Urine cytology was negative for malignancy three times. Serum lactate dehydrogenase was within normal limits, whereas soluble interleukin-2 receptor was elevated at 1,730 U/mL. IgG4-RD was considered as the likely cause. In accordance with current international diagnostic criteria for IgG4-RD, there was: 1) no exclusion criteria, 2) elevated serum IgG4 level, 3) hypocomplementemia, and 4) circumferential soft tissue around the infrarenal aorta. Oral corticosteroid therapy was prescribed. At 40 days post-discharge, follow-up imaging showed a slight reduction in the size of the soft tissue mass. Hypocomplementemia also showed improvement. Conclusion: HT was induced by UTO secondary to suspected IgG4-RD. It is reported that HT due to IgG4-RD occur in over one third of cases. Pathophysiology of HT includes renal parenchymal disease and HN. Laboratory data at admission revealed that the plasma renin activity and plasma aldosterone concentration were normal. His BP was ameliorated after urinary output improved, despite using antihypertensive monotherapy. Thus, we suspected that volume overload due to UTO led to HT. We suggest that HN should be considered as a differential diagnosis for the cause of HT.

Intravenous nicardipine for Japanese patients with acute intracerebral hemorrhage: an individual participant data analysis

The effects of acute systolic blood pressure levels achieved with continuous intravenous administration of nicardipine for Japanese patients with acute intracerebral hemorrhage on clinical outcomes were determined. A systematic review and individual participant data analysis of articles were performed based on prospective studies involving adults developing hyperacute intracerebral hemorrhage who were treated with intravenous nicardipine. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4–6, and hematoma expansion, defined as an increase 6 mL or more from baseline to 24 h computed tomography. Of the total 499 Japanese patients (age 64.9 ± 11.8 years, 183 women, initial BP 203.5 ± 18.3/109.1 ± 17.2 mmHg) studied, death or disability occurred in 35.6%, and hematoma expansion occurred in 15.6%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio 1.25, 95% confidence interval 1.03–1.52 per 10 mmHg) and hematoma expansion (1.49, 1.18–1.87). These odds ratios were relatively high as compared to the reported ones for overall global patients of this individual participant data analysis [1.12 (95% confidence interval 1.00–1.26) and 1.16 (1.02–1.32), respectively]. In conclusion, lower levels of systolic blood pressure by continuous intravenous nicardipine were associated with lower risks of hematoma expansion and 90-day death or disability in Japanese patients with hyperacute intracerebral hemorrhage. The impact of systolic blood pressure lowering on better outcome seemed to be stronger in Japanese patients than the global ones.

Brain Oxygen–Directed Management of Aneurysmal Subarachnoid Hemorrhage. Temporal Patterns of Cerebral Ischemia During Acute Brain Attack, Early Brain Injury, and Territorial Sonographic Vasospasm

Neurocritical management of aneurysmal subarachnoid hemorrhage focuses on delayed cerebral ischemia (DCI) after aneurysm repair. This study conceptualizes the pathophysiology of cerebral ischemia and its management using a brain oxygen-directed protocol (intracranial pressure [ICP] control, eubaric hyperoxia, hemodynamic therapy, arterial vasodilation, and neuroprotection) in patients with subarachnoid hemorrhage, undergoing aneurysm clipping (n = 40). The brain oxygen-directed protocol reduced Lbo2 (Pbto2 [partial pressure of brain tissue oxygen] <20 mm Hg) from 67% to 15% during acute brain attack (<24 hours of ictus), by increasing Pbto2 from 11.31 ± 9.34 to 27.85 ± 6.76 (P < 0.0001) and then to 29.09 ± 17.88 within 72 hours. Day-after-bleed, Fio2 change, ICP, hemoglobin, and oxygen saturation were predictors for Pbto2 during early brain injury. Transcranial Doppler ultrasonography velocities (>20 cm/second) increased at day 2. During DCI caused by territorial sonographic vasospasm (TSV), middle cerebral artery mean velocity (Vm) increased from 45.00 ± 15.12 to 80.37 ± 38.33/second by day 4 with concomitant Pbto2 reduction from 29.09 ± 17.88 to 22.66 ± 8.19. Peak TSV (days 7-12) coincided with decline in Pbto2. Nicardipine mitigated Lbo2 during peak TSV, in contrast to nimodipine, with survival benefit (P < 0.01). Intravenous and cisternal nicardipine combination had survival benefit (Cramer Φ = 0.43 and 0.327; G2 = 28.32; P < 0.001). This study identifies 4 zones of Lbo2 during survival benefit (Cramer Φ = 0.43 and 0.3) TSV, uncompensated; global cerebral ischemia, compensated, and normal Pbto2. Admission Glasgow Coma Scale score (not increased ICP) was predictive of low Pbto2 (β = 0.812, R2 = 0.661, F1,30 = 58.41; P < 0.0001) during early brain injury. Coma was the only credible predictor for mortality (odds ratio, 7.33/>4.8∗; χ2 = 7.556; confidence interval, 1.70-31.54; P < 0.01) followed by basilar aneurysm, poor grade, high ICP and Lbo2 during TSV. Global cerebral ischemia occurs immediately after the ictus, persisting in 30% of patients despite the high therapeutic intensity level, superimposed by DCI during TSV. We propose implications for clinical practice and patient management to minimize cerebral ischemia.

Nicardipine for treating severe antepartum hypertension during pregnancy: Nine years of experience in more than 800 women.

Women with severe hypertension during pregnancy require prompt stabilization with a combination of magnesium sulfate and rapidly acting intravenously administered antihypertensives. It remains unknown which antihypertensive is best suited for pregnancy. The present study evaluated the intravenous use of the calcium antagonist, nicardipine. This multicenter, retrospective case series included all pregnant women beyond 20 weeks of gestation with severe antepartum hypertension that were treated with intravenous nicardipine. successful treatment, time to successful treatment, and maternal safety. Severe hypertension was defined as systolic blood pressure (SBP) of 160 mm Hg or more and/or diastolic blood pressure (DBP) of 110 mm Hg or more. This study included 830 women. After 1 h of treatment, two-thirds of the women had SBP below 160 mm Hg and DBP below 100 mm Hg. In three out of four women, the mean arterial pressure was below 120 mm Hg. Within 2 h of treatment, 77.4% of women achieved successful treatment. In all cases, nicardipine was eventually effective. Within the first 2 h, 42.7% of women experienced temporary low DBP (ie below 70 mm Hg) without clinical consequences for the mother or fetus. In all cases, the low DBP resolved after discontinuing or reducing the dosage of nicardipine. One case of fetal distress was attributable to maternal hypotension, and a cesarean section was performed at more than 2 h after initiating therapy. During treatment, headache, nausea, and vomiting decreased significantly. To date, this was the largest case-series study on the use of nicardipine for treating severe antepartum hypertension in pregnancy. We found that nicardipine could effectively and safely treat this condition. Based on its high success rate and acceptable safety profile, nicardipine should be considered a first-line treatment in women with severe hypertension in pregnancy.

Design of the BEST‐II Randomized Clinical Trial

Background Prior observational studies indicate that lower systolic blood pressure (SBP) after successful endovascular treatment (EVT) is associated with better functional outcomes in patients with acute ischemic stroke. However, whether targeting SBP to levels below the guideline‐recommended target of ≤180 mm Hg is safe and efficacious remains to be determined. Methods The BEST (Blood Pressure After Endovascular Stroke Therapy)‐II trial (NCT04116112) is a pragmatic, phase 2, multisite, prospective, randomized, open‐label trial with blinded end‐point assessment designed to (1) compare the safety of lower SBP targets with higher SBP targets in successfully EVT‐treated patients with stroke and (2) inform the design and estimate the probability of success of a future phase 3 trial. A total of 120 patients with acute ischemic stroke who undergo successful EVT (final modified Thrombolysis in Cerebral Infarction score ≥2b) for intracranial internal carotid artery or M1 or M2 segment of the middle cerebral artery will be randomized to the SBP targets of ≤180, &lt;160, and &lt;140 mm Hg, to be maintained for 24 hours using intravenous nicardipine as the first‐line agent. We will assess the harm of decreased post‐EVT SBP by quantifying its linear relationship with multiple primary outcomes of final infarct volume on magnetic resonance imaging (or computed tomography) at 36 hours and utility‐weighted modified Rankin scale score at 90 days. The study is approved by the Institutional Review Boards of both participating institutions and the Data and Safety Monitoring Board. Results Enrollment in the BEST‐II trial began in January 2020, with 90 patients enrolled as of October 13, 2021. The trial is progressing ahead of target, with an anticipated enrollment completion date before January 2023. Conclusions The BEST‐II trial results will inform the stroke community of the safety of lower SBP targets in patients with acute ischemic stroke who are successfully treated with EVT and will demonstrate the feasibility of both achieving lower blood pressure targets as well as conducting an efficacy trial. Trial enrollment is on target despite the COVID‐19 pandemic. Clinical Trial Registration Information NCT04116112 ( https://clinicaltrials.gov/ct2/show/NCT04116112 )

Temporal Trajectory of Systolic Blood Pressure and Outcomes in Acute Intracerebral Hemorrhage: ATACH-2 Trial Cohort.

Background:To highlight the heterogeneity of acute temporal blood pressure (BP) changes in the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) and associations with the outcomes of intracerebral hemorrhage.Methods:One thousand patients with acute intracerebral hemorrhage, who had been randomized to intensive (110–139 mm Hg) or standard (140–179 mm Hg) systolic BP (SBP) lowering with intravenous nicardipine in ATACH-2 from 2011 to 2015, were analyzed about temporal changes in hourly maximum SBP up to 24 hours after randomization using group-based trajectory modeling. Outcomes included death or disability (modified Rankin Scale score 4–6) at 3 months, neurological deterioration within 24 hours (≥2-point decrease in Glasgow Coma Scale score or ≥4-point increase in National Institutes of Health Stroke Scale score), and acute kidney injury (≥0.3 mg/dL within 48 hours or ≥1.5-fold increase in serum creatinine) within 7 days after onset.Results:Group-based trajectory modeling revealed 4 SBP trajectory groups: moderate SBP (from ≈190 mm Hg at hospital arrival to 150–160 mm Hg after randomization; n=298), moderate-to-low SBP (from ≈190 mm Hg to <140 mm Hg; n=395), high-to-low SBP (from >210 mm Hg to <140 mm Hg; n=134), and high SBP (from >210 mm Hg to 160–170 mm Hg; n=173). Patients with intensive treatment accounted for 11.1%, 88.6%, 85.1%, and 1.7% of each group, respectively. Compared with the moderate-to-low SBP group, the high-to-low SBP group showed increased risks of death or disability at 3 months (adjusted odds ratio, 2.29 [95% CI, 1.24–4.26]) and acute kidney injury (adjusted odds ratio, 3.50 [95% CI, 1.83–6.69]), while no increase in neurological deterioration was seen in this group (adjusted odds ratio, 0.48 [95% CI, 0.20–1.13]). The moderate SBP and high SBP groups showed no significant risk differences for such outcomes.Conclusions:Data-driven observation using a group-based trajectory modeling approach may be useful to clarify the relationship between antihypertensive treatment, temporal SBP changes, and outcomes in acute intracerebral hemorrhage.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01176565.

Clinical efficacy and safety of two concentrations of intravenous nicardipine hydrochloride for nicardipine-related phlebitis in patients with preeclampsia.

To evaluate the effect of two concentrations of intravenous administration of nicardipine hydrochloride on nicardipine-related phlebitis in patients with preeclampsia. A total of 100 preeclampsia patients were administered with nicardipine hydrochloride and divided into the low-concentration (LC) and high-concentration (HC) groups. The incidence and severity of phlebitis, time from treatment to onset of phlebitis, skin temperature, visual analogue scale (VAS) score, induration, and systemic adverse reactions were compared between two groups. The incidence rate of phlebitis in the LC group was 20% (10/50), significantly lower than 42% (21/50) in the HC group (P< 0.05). Ridit Analysis showed that the severity of phlebitis in the LC group was remarkably lower than that in the HC group (P< 0.05). In the LC group, the time from intravenous administration to onset of phlebitis was longer, the average skin temperature was higher, the VAS score was lower, and the indurated area was smaller than those in the HC group (all P< 0.05). Intravenous infusion of nicardipine hydrochloride with constant and low concentration reduces the incidence rate of phlebitis, prolongs the time from treatment to onset of phlebitis, alleviates the severity of phlebitis and pain, maintains skin temperature, and minimizes induration in preeclampsia patients without systemic adverse reactions.

Lessons Learned from Phase II and Phase III Trials Investigating Therapeutic Agents for Cerebral Ischemia Associated with Aneurysmal Subarachnoid Hemorrhage.

One of the challenges in bringing new therapeutic agents (since nimodipine) in for the treatment of cerebral ischemia associated with aneurysmal subarachnoid hemorrhage (aSAH) is the incongruence in therapeutic benefit observed between phase II and subsequent phase III clinical trials. Therefore, identifying areas for improvement in the methodology and interpretation of results is necessary to increase the value of phase II trials. We performed a systematic review of phase II trials that continued into phase III trials, evaluating a therapeutic agent for the treatment of cerebral ischemia associated with aSAH. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for systematic reviews, and review was based on a peer-reviewed protocol (International Prospective Register of Systematic Reviews no. 222965). A total of nine phase III trials involving 7,088 patients were performed based on eight phase II trials involving 1558 patients. The following therapeutic agents were evaluated in the selected phase II and phase III trials: intravenous tirilazad, intravenous nicardipine, intravenous clazosentan, intravenous magnesium, oral statins, and intraventricular nimodipine. Shortcomings in several design elements of the phase II aSAH trials were identified that may explain the incongruence between phase II and phase III trial results. We suggest the consideration of the following strategies to improve phase II design: increased focus on the selection of surrogate markers of efficacy, selection of the optimal dose and timing of intervention, adjustment for exaggerated estimate of treatment effect in sample size calculations, use of prespecified go/no-go criteria using futility design, use of multicenter design, enrichment of the study population, use of concurrent control or placebo group, and use of innovative trial designs such as seamless phase II to III design. Modifying the design of phase II trials on the basis of lessons learned from previous phase II and phase III trial combinations is necessary to plan more effective phase III trials.

C95. The electrocardiographic changes in a hypertensive COVID-19 patient who received beta-blocker and favipiravir: a case report

BackgroundVarious electrocardiographic manifestations have been reported in COVID-19 which either result from myocarditis or insult-induced re-emerging of pre-existing condition. Some antiviruses used off-labelly for COVID-19, including favipiravir, are considered to be proarrhythmic. Meanwhile, anti-hypertensive drugs such as beta-blocker may induce bradyarrhythmia.Case SummaryA 69-year-old male with confirmed COVID-19 and a history of uncontrolled hypertension presented with blood pressure of 216/111mmHg at admission. No sign and symptom of acute target organ damage had been reported. His electrocardiography showed normal sinus rhythm (heart rate [HR] 60bpm). The echocardiographic finding revealed normal heart function. He received favipiravir for 5 days, intravenous nicardipine (0.5mcg/kgBW/hour), and peroral amlodipine (1x10mg), candesartan (1x16mg), and bisoprolol (1x2.5mg). During hospitalization, the HR fluctuated between 52-109. On the sixth day, a total atrioventricular (AV) block with junctional escape rhythm (HR 66bpm) was present. Both favipiravir and bisoprolol were ceased simultaneously. The AV block persisted for 4 days then transformed into a junctional rhythm for the next 3 days and sinus bradycardia (HR 48bpm) thereafter. No pacing was performed.DiscussionThe possible differential diagnoses in this case include sick sinus syndrome (SSS), COVID-19-induced myocarditis, and drug-induced. The SSS might explain the wide variability of the HR. There were some reports presenting the sinus node dysfunction as a manifestation of SARS-CoV-2 infection. Further evaluation using Holter and/or electrophysiological study is warranted. Drug-induced cause may be excluded because the bradyarrhythmia remained after the cessation of both beta-blocker and favipiravir.

C95. The electrocardiographic changes in a hypertensive COVID-19 patient who received beta-blocker and favipiravir: a case report

BackgroundVarious electrocardiographic manifestations have been reported in COVID-19 which either result from myocarditis or insult-induced re-emerging of pre-existing condition. Some antiviruses used off-labelly for COVID-19, including favipiravir, are considered to be proarrhythmic. Meanwhile, anti-hypertensive drugs such as beta-blocker may induce bradyarrhythmia.Case SummaryA 69-year-old male with confirmed COVID-19 and a history of uncontrolled hypertension presented with blood pressure of 216/111mmHg at admission. No sign and symptom of acute target organ damage had been reported. His electrocardiography showed normal sinus rhythm (heart rate [HR] 60bpm). The echocardiographic finding revealed normal heart function. He received favipiravir for 5 days, intravenous nicardipine (0.5mcg/kgBW/hour), and peroral amlodipine (1x10mg), candesartan (1x16mg), and bisoprolol (1x2.5mg). During hospitalization, the HR fluctuated between 52-109. On the sixth day, a total atrioventricular (AV) block with junctional escape rhythm (HR 66bpm) was present. Both favipiravir and bisoprolol were ceased simultaneously. The AV block persisted for 4 days then transformed into a junctional rhythm for the next 3 days and sinus bradycardia (HR 48bpm) thereafter. No pacing was performed.DiscussionThe possible differential diagnoses in this case include sick sinus syndrome (SSS), COVID-19-induced myocarditis, and drug-induced. The SSS might explain the wide variability of the HR. There were some reports presenting the sinus node dysfunction as a manifestation of SARS-CoV-2 infection. Further evaluation using Holter and/or electrophysiological study is warranted. Drug-induced cause may be excluded because the bradyarrhythmia remained after the cessation of both beta-blocker and favipiravir.