Naphthalimide functionalized metal-organic framework for rapid and nanomolar level detection of hydrazine and anti-hypertensive drug nicardipine.

The increasing utilization of hydrazine and its derivatives across diverse sectors highlights the pressing need for efficient detection methods to safeguard human health and the environment. Likewise, nicardipine, a widely used medication for heart diseases, necessitates accurate sensing techniques for clinical research and therapeutic monitoring. Here, we propose a novel approach using a naphthalimide-functionalized Zr-MOF as a fluorometric probe capable of detecting both hydrazine and nicardipine in aqueous medium. Our designed probe exhibited a significant 31-fold increase in fluorescence intensity upon interaction with hydrazine. At the same time, nicardipine induced 86% fluorescence quenching with an exceptionally rapid response time (100 s for hydrazine and 5 s for nicardipine). The designed probe has the ability to detect both analytes at nanomolar concentrations (LOD for hydrazine is 1.11 nM while that for nicardipine is 9.6 nM). Investigation across various wastewater samples and pH conditions further validated its practical utility. The mechanism behind fluorometric sensing of nicardipine was thoroughly investigated using modern instrumentation. Our study presents a versatile and effective approach for detecting hydrazine and nicardipine, addressing crucial needs in both industrial and biomedical contexts.

Optimizing nicardipine dosage for effective control of pituitrin-induced hypertension in laparoscopic myomectomy undergoing total intravenous anesthesia.

BACKGROUND: This study aimed to determine the median effective dose (ED50) and 95% effective dose (ED95) of nicardipine for treating pituitrin-induced hypertension during laparoscopic myomectomy, providing guidance for the management of intraoperative blood pressure in such patients. METHODS: Among the initial 40 participants assessed, 24 underwent elective laparoscopic myomectomy. A sequential up-and-down method was employed to ascertain the ED50 of nicardipine based on its antihypertensive efficacy. Nicardipine was initially administered at 6 µg/kg following the diagnosis of pituitrin-induced hypertension in the first patient. Dosing adjustments were made to achieve the desired antihypertensive effect, restoring systolic blood pressure and heart rate to within ± 20% of baseline within 120 s. The dosing increment or reduction was set at 0.5 µg/kg for effective or ineffective responses, respectively. The ED50 and ED95 of nicardipine were calculated using Probit regression by Maximum Likelihood Estimation (MLE) to establish dose-response curves and confidence intervals. RESULTS: 24 patients were included for analysis finally. The ED50 and ED95 of nicardipine for blood pressure control after pituitrin injection were determined. The study found that the ED50 of nicardipine for treating pituitrin-induced hypertension was 4.839 µg/kg (95% CI: 4.569-5.099 µg/kg), and the ED95 was estimated at 5.308 µg/kg (95% CI: 5.065-6.496 µg/kg). Nicardipine effectively mitigated the hypertensive response caused by pituitrin without inducing significant tachycardia or hypotension. CONCLUSIONS: Nicardipine effectively controlled blood pressure after pituitrin injection during laparoscopic myomectomy, with ED50 and ED95 values established. This research highlights the potential utility of nicardipine in addressing hypertensive responses induced by pituitrin, particularly in clinical settings where pituitrin is routinely administered.

Nicardipine constant rate infusion alleviates the cardiovascular effects of dexmedetomidine infusions without affecting the minimal alveolar concentration in sevoflurane-anesthetized dogs.

Two randomized crossover trials evaluated the effects of nicardipine constant rate infusion (CRI) on 1) the anesthetic potency of sevoflurane and 2) the ability to attenuate dexmedetomidine-induced cardiovascular depression in anesthetized dogs. First, six healthy Beagle dogs weighing 11.7 ± 0.9 kg were allocated to one of three treatments that administered a CRI of carrier (saline) or dexmedetomidine 0.5 or 3.0 µg/kg/h following a loading dose. The minimum alveolar concentration (MAC) of sevoflurane was determined utilizing electric stimuli before and after the loading dose of nicardipine (20 µg/kg intravenously for 10 min), followed by CRI at 40 µg/kg/h with 60 min of equilibration. Subsequently, cardiovascular and blood gas variables were evaluated in another trial under sevoflurane anesthesia at the individual 1.5 MAC. After baseline measurements, the dogs were assigned to two treatments (dexmedetomidine CRI at 0.5 or 3.0 µg/kg/h following a loading dose) with sevoflurane doses adjusted to 1.5 times of MAC equivalent, and the measurements were repeated every 15 min for 120 min. After 60 min, nicardipine CRI at 40 µg/kg/h with a loading dose was added to the dexmedetomidine CRI. Dexmedetomidine infusions significantly decreased the sevoflurane MAC but nicardipine did not significantly alter the MAC either with or without dexmedetomidine CRI in dogs. Dexmedetomidine dose-dependently decreased the cardiac index and increased the systemic vascular resistance index; these effects were fully counteracted by concomitant nicardipine CRI. Nicardipine CRI can be useful for controlling the cardiovascular depression elicited by dexmedetomidine in anesthetized dogs without affecting the anesthetic potency of sevoflurane.

Correlations between heart sound components and hemodynamic variables.

Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.

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.

Direct investigations of the effects of nicardipine on calcium channels of astrocytes by Atomic Force Microscopy.

Calcium channel blockers (CCB) of astrocytes can blockade the calcium ions entry through the voltage gated calcium channels (VGCC), and is widely used in the diseases related with VGCC of astrocytes. But many aspects of the interaction mechanisms between the CCB and VGCC of astrocytes still remain unclear due to the limited resolution of the approaches. Herein the effects of the nicardipine (a type of CCB) on VGCC of astrocytes were investigated at very high spatial, force and electrical resolution by multiple modes of Atomic Force Microscopy (AFM) directly. The results reveal that after the addition of nicardipine, the recognition signals of VGCC disappeared; the specific unbinding forces vanished; the conductivity of the astrocytes decreased (the current decreased about 2.9 pA and the capacitance was doubled); the surface potential of the astrocytes reduced about 14.2 mV. The results of electrical properties investigations are consistent with the simulation experiments. The relations between these biophysical and biochemical properties of VGCC have been discussed. All these demonstrate that the interactions between nicardipine and VGCC have been studied at nanometer spatial resolution, at picoNewton force resolution and very high electrical signal resolution (pA in current, pF in capacitance and 0.1 mV in surface potential) level. The approaches are considered to be high resolution and high sensitivity, and will be helpful and useful in the further investigations of the effects of other types of CCB on ion channels, and will also be helpful in the investigations of mechanisms and therapy of ion channelopathies.

Cisternal nicardipine for prevention of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a comparative retrospective cohort study.

PURPOSE: Intrathecal vasoactive drugs have been proposed in patients with aneurysmal subarachnoid hemorrhage (aSAH) to manage cerebral vasospasm (CV). We analyzed the efficacy of intracisternal nicardipine compared to intraventricular administration to a control group (CG) to determine its impact on delayed cerebral ischemia (DCI) and functional outcomes. Secondary outcomes included the need for intra-arterial angioplasties and the safety profile. METHODS: We performed a retrospective analysis of prospectively collected data of all adult patients admitted for a high modified Fisher grade aSAH between January 2015 and April 2022. All patients with significant radiological CV were included. Three groups of patients were defined based on the CV management: cisternal nicardipine (CN), ventricular nicardipine (VN), and no intrathecal nicardipine (control group). RESULTS: Seventy patients met the inclusion criteria. Eleven patients received intracisternal nicardipine, 18 intraventricular nicardipine, and 41 belonged to the control group. No cases of DCI were observed in the CN group (p = 0.02). Patients with intracisternal nicardipine had a reduced number of intra-arterial angioplasties when compared to the control group (p = 0.03). The safety profile analysis showed no difference in complications across the three groups. Intrathecal (ventricular or cisternal) nicardipine therapy improved functional outcomes at 6 months (p = 0.04) when compared to the control group. CONCLUSION: Administration of intrathecal nicardipine for moderate to severe CV reduces the rate of DCI and improved long-term functional outcomes in patients with high modified Fisher grade aSAH. This study also showed a relative benefit of cisternal over intraventricular nicardipine, thereby reducing the number of angioplasties performed in the post-treatment phase. However, these preliminary results should be confirmed with future prospective studies.

Nicardipine or Nitroprusside for Postoperative Blood Pressure Control in Infants After Surgery for Congenital Heart Disease: Single-Center Retrospective Noninferiority and Cost Analysis, 2016-2020.

OBJECTIVES: Postoperative hypertension frequently occurs after surgery for congenital heart disease. Given safety concerns when using calcium channel blockers in infants along with the cost and side-effect profile of nitroprusside, we retrospectively assessed our experience of using nicardipine and nitroprusside for postoperative blood pressure control in infants who underwent surgery for congenital heart disease. We also investigated the cost difference between the medications. DESIGN: This study was a single-center retrospective, pre-post chart review of patients who had surgery for congenital heart disease between 2016 and 2020. The primary aim was a noninferiority comparison of achievement of blood pressure goal at 1-hour post-initiation of an antihypertensive agent. Secondary comparisons included achievement of blood pressure goal at 2 hours after medication initiation, Vasoactive-Inotropic Score (VIS), and blood transfusion, crystalloid volume, and calcium needs. SETTING: Academic quaternary-care center. PATIENTS: Infants under 1 year old who required treatment for hypertension with nitroprusside ( n = 71) or nicardipine ( n = 52) within 24 hours of surgery for congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We failed to identify any difference in proportion of patients that achieved blood pressure control at 1-hour after medication initiation (nitroprusside 52% vs. nicardipine 54%; p = 0.86), with nicardipine noninferior to nitroprusside within a 15% margin. Of patients who did not achieve control at 1-hour post-medication initiation, receiving nicardipine was associated with blood pressure control at 2 hours post-medication initiation (79% vs. 38%; p = 0.003). We also failed to identify an association between antihypertensive types and mean VIS scores, blood transfusion volumes, crystalloid volumes, and quantities of calcium administered. Index cost of using nitroprusside was 16 times higher than using nicardipine, primarily due to difference in wholesale cost. CONCLUSIONS: In our experience of achieving blood pressure control in infants after surgery for congenital heart disease (2016-2020), antihypertensive treatment with nicardipine was noninferior to nitroprusside. Furthermore, nicardipine use was significantly less expensive than nitroprusside. Our contemporary practice is therefore to use nicardipine in preference to nitroprusside.

Transdermal application of H100 gel to the penile shaft in patients with Peyronie's disease infiltrates the tunica albuginea.

Treatment options for Peyronie's disease (PD) remain limited. Topical H100 gel, (Hybrid Medical, Edina, USA), which contains nicardipine, super oxide dismutase and emu oil showed safety and efficacy in a previous small double-blind placebo-controlled pilot study. The present study evaluates if topically applied H100 gel applied to the penile shaft infiltrates the tunica albuginea. Nicardipine is a key active ingredient in H100 and serves as a surrogate marker. Three men already scheduled to undergo a planned surgical procedure for PD applied commercially available H100 gel twice daily to the penile shaft for up to 30 days prior to the procedure. Tunica albuginea samples were obtained at surgery. Nicardipine evaluation was performed using isotope dilution technique via liquid-chromatograph-mass spectrometry (LCMS). All three patients tolerated H100 gel application without side effects. All three tunica albuginea specimens showed detectable nicardipine in the tunical tissue. Transdermal application of commercially available H100 gel is able to penetrate the tunica albuginea tissue and is detectable in men with acute and chronic PD. This finding may support the encouraging results found in the prior H100 pilot study.

Blood pressure lowering enhances cerebrospinal fluid efflux to the systemic circulation primarily via the lymphatic vasculature.

BACKGROUND: Inside the incompressible cranium, the volume of cerebrospinal fluid is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering on fluorescent cerebrospinal fluid tracer absorption into the systemic blood circulation. METHODS: Blood pressure lowering was performed by an i.v. administration of nitric oxide donor (sodium nitroprusside, 5 µg kg-1 min-1) or the Ca2+-channel blocker (nicardipine hydrochloride, 0.5 µg kg-1 min-1) for 10, and 15 to 40 min, respectively. The effect of blood pressure lowering on cerebrospinal fluid clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. The effect of nicardipine on cerebral hemodynamics was investigated by near-infrared spectroscopy. The distribution of cerebrospinal fluid tracers (40 kDa horse radish peroxidase,160 kDa nanogold-conjugated IgG) in exit pathways was also analyzed at an ultrastructural level using electron microscopy. RESULTS: Nicardipine and sodium nitroprusside reduced blood pressure by 32.0 ± 19.6% and 24.0 ± 13.3%, while temporarily elevating intracranial pressure by 14.0 ± 7.0% and 18.2 ± 15.0%, respectively. Blood pressure lowering significantly increased tracer accumulation into dorsal dura, deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by blood pressure lowering into the systemic circulation was markedly reduced (- 66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes. CONCLUSIONS: This is the first study showing that cerebrospinal fluid clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced cerebrospinal fluid clearance by blood pressure lowering may have therapeutic potential in diseases with dysregulated cerebrospinal fluid  flow.

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

BACKGROUND: Nicardipine 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). METHODS: This 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. RESULTS: Of 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. CONCLUSION: In 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.

Naphazoline intoxication managed with minimally invasive cardiac output monitoring.

Naphazoline, a nonspecific alpha-adrenoceptor stimulant, is a potent vasoconstrictor used in nasal sprays, eye drops, and over-the-counter antiseptics. Naphazoline intoxication increases afterload by constricting the peripheral arteries, which can lead to complications including multiple organ failure. Although phentolamine, a nonselective alpha-adrenoceptor antagonist, and nicardipine, a calcium channel blocker, are used for the treatment of naphazoline intoxication, no established administration protocols currently exist. We present the case of a 32-year-old male with depression who ingested 150 mL of an antiseptic containing 0.1% naphazoline (equivalent to 150 mg of naphazoline). Five hours after ingestion, the patient was admitted to hospital exhibiting signs of naphazoline intoxication, such as bradycardia (46 beats/min), blood pressure of 166/122 mmHg, and peripheral cyanosis. We used the FloTrac™/EV1000™ system (Edwards Lifesciences, Irvine, CA, USA), a minimally invasive cardiac output monitoring system, to monitor systemic vascular resistance. The systemic vascular resistance index (SVRI) was elevated (4457 dyne.s/cm5/m2; nomal range: 1970-2390 dyne.s/cm5/m2) upon admission and initial treatment with continuous intravenous infusion of phentolamine led to SVRI normalization within 2 h. With the goal of maintaining SVRI normalization, continuous infusion with nicardipine was then started. At 10 h after treatment initiation, the nicardipine dose peaked at 9 mg/h (1.9 µg/kg/min). Treatment was discontinued 8 h later, and the patient was discharged on the fourth day without sequelae. In conclusion, the use of a minimally invasive cardiac output monitoring system to track vascular resistance can effectively guide the dosing of phentolamine or nicardipine in the treatment of naphazoline intoxication.

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.

HummingFlow: novel single twist-drill access for ventricular drainage, irrigation, monitoring, and automated local drug delivery in subarachnoid hemorrhage.

OBJECTIVE: The management of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH) remains one of the most important targets for neurocritical care. Advances in monitoring technology have facilitated a more thorough understanding of the pathophysiology and therapeutic approaches, but interventions are generally limited to either systemic therapies or passive CSF drainage. The authors present a novel approach that combines a multimodal monitoring bolt-based system with an irrigating ventricular drain capable of delivering intrathecal medications and describe their early experience in patients with aSAH. METHODS: The authors performed a retrospective review of cases treated with the combined Hummingbird multimodal bolt system and the IRRAflow irrigating ventriculostomy. RESULTS: Nine patients were treated with the combined multimodal bolt system with irrigating ventriculostomy approach. The median number of days to clearance of the third and fourth ventricles was 3 days in patients with obstructive intraventricular hemorrhage. Two patients received intrathecal alteplase for intraventricular hemorrhage clearance, and 2 patients received intrathecal nicardipine as rescue therapy for severe symptomatic angiographic vasospasm. CONCLUSIONS: Combined CSF drainage, irrigation, multimodality monitoring, and automated local drug delivery are feasible using a single twist-drill hole device. Further investigation of irrigation settings and treatment approaches in high-risk cases is warranted.

Nicardipine is a putative EED inhibitor and has high selectivity and potency against chemoresistant prostate cancer in preclinical models.

BACKGROUND: It is imperative to develop novel therapeutics to overcome chemoresistance, a significant obstacle in the clinical management of prostate cancer (PCa) and other cancers. METHODS: A phenotypic screen was performed to identify novel inhibitors of chemoresistant PCa cells. The mechanism of action of potential candidate(s) was investigated using in silico docking, and molecular and cellular assays in chemoresistant PCa cells. The in vivo efficacy was evaluated in mouse xenograft models of chemoresistant PCa. RESULTS: Nicardipine exhibited high selectivity and potency against chemoresistant PCa cells via inducing apoptosis and cell cycle arrest. Computational, molecular, and cellular studies identified nicardipine as a putative inhibitor of embryonic ectoderm development (EED) protein, and the results are consistent with a proposed mechanism of action that nicardipine destabilised enhancer of zeste homologue 2 (EZH2) and inhibited key components of noncanonical EZH2 signalling, including transducer and activator of transcription 3, S-phase kinase-associated protein 2, ATP binding cassette B1, and survivin. As a monotherapy, nicardipine effectively inhibited the skeletal growth of chemoresistant C4-2B-TaxR tumours. As a combination regimen, nicardipine synergistically enhanced the in vivo efficacy of docetaxel against C4-2 xenografts. CONCLUSION: Our findings provided the first preclinical evidence supporting nicardipine as a novel EED inhibitor that has the potential to be promptly tested in PCa patients to overcome chemoresistance and improve clinical outcomes.

The effect on vital signs of concomitant administration of nicardipine and dexmedetomidine sedation after spinal anesthesia: A double-blind, randomized controlled trial.

BACKGROUND: We evaluated heart rate (HR) and blood pressure (BP) trends when nicardipine (NCD) was co-administered during dexmedetomidine (DEX) sedation after spinal anesthesia. METHODS: Sixty patients aged 19 to 65 were randomly assigned to the DEX or DEX-NCD groups. Five minutes after infusion of the loading dose of DEX, the NCD was administered intravenously at a rate of 5 µg/kg for 5 minutes in the DEX-NCD group. The study starting point was set at 0 minute when the DEX loading dose was initiated. The primary outcomes were the differences in HR and BP between the 2 groups during the study drug administration. Secondary outcomes included the number of patients whose HR was < 50 beats per minute (bpm) after the DEX loading dose infusion, and associated factors were evaluated. The incidence of hypotension in the postanesthesia care unit, postanesthesia care unit length of stay, postoperative nausea and vomiting, postoperative urinary retention, time to first urination after spinal anesthesia, acute kidney injury, and postoperative hospital length of stay were evaluated. RESULTS: The HR was significantly higher at 14 minutes, and the mean BP was significantly lower at 10 minutes in the DEX-NCD group than in the DEX group. The number of patients with an HR < 50 bpm during surgery was significantly higher in the DEX group than in the DEX-NCD group at 12, 16, 24, 26, and 30 minutes. The DEX group and a low initial HR were independently associated with the occurrence of an HR < 50 bpm after DEX loading dose infusion. Postoperative outcomes were not significantly different between the 2 groups. CONCLUSIONS: Simultaneous administration of NCD during the administration of a loading dose of DEX prevented severe bradycardia. Co-administration of NCD may be considered in patients with a low initial HR when severe bradycardia is expected during the DEX loading dose infusion. NCD and DEX may be safely infused simultaneously without affecting postoperative complications (see Figure S1, Supplemental Digital Content, http://links.lww.com/MD/J241 , Graphical abstract).

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.

Therapeutic and safety outcomes of intracoronary nicardipine in coronary artery disease patients: a systematic review.

Aim: This systematic review aimed to shed light on the efficacy of intracoronary (IC) nicardipine in treating no reflow with CAD undergoing revascularization. Methods: Literature search was performed on databases with following eligibility criteria: adult patients with CAD; clinical trials or observational studies; IC nicardipine as intervention; therapeutic and safety outcome reported. Results: A total of 1249 papers were yielded during the literature search. Of these, 11 studies were finalized for this systematic review. Complete restoration of TIMI 3 flow was observed in 98.6% of the patients receiving IC nicardipine. A significant increase in the CBF after infusion of IC nicardipine (p < 0.05) was also observed. Conclusion: IC nicardipine significantly increases CBF and decreases coronary vascular resistance.

Coronary artery disease (CAD) is a condition that results in the narrowing or blockage of heart arteries. Arteries are blood vessels that bring oxygen-rich blood from your heart to the rest of your body's cells. We aimed to evaluate the effects of intracoronary (IC) nicardipine, a drug that blocks calcium from entering the muscle cells and blood vessels of the heart, which causes the vessels to relax and widen, allowing for blood to flow more easily, on a phenomenon known as coronary slow flow (CSF). CSF is defined as a delayed widening of the blood vessels of the heart. CSF or the no reflow phenomenon is a major negative complication associated with surgical procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), both of which are used to open up blocked arteries. The systematic search identified studies that evaluated the effect of IC nicardipine in patient during CAD treatment, undergoing PCI, CABG, or having confirmed or suspected narrowing of the aortic valve or one of the four valves of the heart, which results in restricted blood flow from the heart to the body. From the results of studies discussed in the review, it can be concluded that IC nicardipine significantly increases blood flow to the heart and can help prevent the no reflow phenomenon in patients undergoing PCI. Nicardipine proved to be a safe and effective option in the management of complications such as no reflow in patients receiving therapies to restore blood flow following CAD.