Administration Of Nicardipine Research Articles

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.

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

We evaluated heart rate (HR) and blood pressure (BP) trends when nicardipine (NCD) was co-administered during dexmedetomidine (DEX) sedation after spinal anesthesia. 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. 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. 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).

Microvascular Cerebral Blood Flow Monitoring Detects Response to Intrathecal Nicardipine Treatment for Vasospasm (S4.005)

<h3>Objective:</h3> Determining the effect of intrathecal nicardipine on microvascular cerebral blood flow <h3>Background:</h3> A common complication of subarachnoid hemorrhage is cerebral vasospasm, which is associated with delayed cerebral ischemia (DCI), a predictor of poor functional outcome. Intrathecal administration of nicardipine (ITn) upon detection of vasospasm holds promise as a treatment that reduces the incidence of secondary stroke. Herein, we utilize a novel non-invasive optical measurement of regional microvascular perfusion to determine the effect of ITn on microvascular cerebral blood flow (CBF). <h3>Design/Methods:</h3> In this observational study, we prospectively studied 20 patients with non-traumatic subarachnoid hemorrhage who were treated with ITn as part of usual care for evolving cerebral vasospasm. Regional microvascular CBF in the frontal cortex was measured with diffuse correlation spectroscopy for up to 90 min after the first treatment dose, and for a subset of patients, on days 2 and 3 of treatment as well. Outcome was assessed as the presence of DCI on imaging. <h3>Results:</h3> CBF increased significantly over the 90 min of monitoring after the first and subsequent doses (p&lt;0.001) in the absence of systemic hemodynamic changes. In general, the CBF response was heterogeneous across subjects. Using data from the first dose, a latent class mixture model was used to classify 19/20 patients into two distinct classes of cerebral blood flow response: patients in class 1 (n=6) showed a decrease or no change in CBF, while patients in class 2 (n=13) showed a pronounced increase in CBF in response to nicardipine. The incidence of DCI was 5/6 in class 1 and 0/13 in class 2 (p&lt;0.001). Similar significant differences in CBF response in patients with and without DCI were also observed on days 2 and 3 (both p&lt;0.001). <h3>Conclusions:</h3> Microvascular CBF monitoring is feasible in critically ill subarachnoid hemorrhage patients. CBF response may provide a valuable biomarker for treatment responsiveness. <b>Disclosure:</b> Dr. Sathialingam has nothing to disclose. Mr. Cowdrick has nothing to disclose. Ms. Urner has nothing to disclose. Ms. Liew has nothing to disclose. Dr. Sigman has nothing to disclose. Dr. Akbik has nothing to disclose. Dr. Samuels has received publishing royalties from a publication relating to health care. Dr. Kandiah has nothing to disclose. Dr. Buckley has received research support from Global Blood Therapeutics. Dr. Buckley has received research support from NIH. Ofer Sadan has received intellectual property interests from a discovery or technology relating to health care.

Microvascular cerebral blood flow response to intrathecal nicardipine is associated with delayed cerebral ischemia.

One of the common complications of non-traumatic subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI). Intrathecal (IT) administration of nicardipine, a calcium channel blocker (CCB), upon detection of large-artery cerebral vasospasm holds promise as a treatment that reduces the incidence of DCI. In this observational study, we prospectively employed a non-invasive optical modality called diffuse correlation spectroscopy (DCS) to quantify the acute microvascular cerebral blood flow (CBF) response to IT nicardipine (up to 90 min) in 20 patients with medium-high grade non-traumatic SAH. On average, CBF increased significantly with time post-administration. However, the CBF response was heterogeneous across subjects. A latent class mixture model was able to classify 19 out of 20 patients into two distinct classes of CBF response: patients in Class 1 (n = 6) showed no significant change in CBF, while patients in Class 2 (n = 13) showed a pronounced increase in CBF in response to nicardipine. The incidence of DCI was 5 out of 6 in Class 1 and 1 out of 13 in Class 2 (p < 0.001). These results suggest that the acute (<90 min) DCS-measured CBF response to IT nicardipine is associated with intermediate-term (up to 3 weeks) development of DCI.

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-R06-4: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME TRIGGERED BY FLUID RETENTION AND HYPERTENSION AFTER STEROID INITIATION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

Objectives: Central nervous system (CNS) involvement in antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis is common, with hypertrophic pachymeninges, cerebrovascular events, hypophysitis, or posterior reversible encephalopathy syndrome (PRES) being the most common CNS presentations. Design and Methods: Case report. Results: A 73-year-old Japanese woman presented with a fever and cough. The patient had no relevant medical history. Her c-reactive protein (CRP) level increased to 22.38 mg/dl, and meropenem was initiated; however, her fever and CRP levels did not improve. Furthermore, creatinine level increased from 0.83 to 3.44 mg/dl during hospitalization. She was transferred to our hospital for evaluation of renal function deterioration. Her consciousness level was alert, and her blood pressure was 140/80 mm Hg. A renal biopsy was performed, and histological examination of the kidneys revealed diffuse pauci-immune necrotizing and crescentic glomerulonephritis. Myeloperoxidase (MPO) -ANCA was 2.9 IU/mL and proteinase 3 (PR3) -ANCA was negative. On the basis of these findings, the patient was diagnosed with ANCA-associated vasculitis. On the fourth hospital day, she was treated with 500 mg intravenous methylprednisolone, once daily, for 3 days, followed by oral prednisolone (40 mg; 0.8 mg/kg). Although her fever and CRP levels improved after the initiation of immunosuppressive therapy, she required renal replacement therapy on the eighth hospital day. Rituximab (500 mg) was administered on the ninth hospital day. Her blood pressure subsequently increased, with the systolic blood pressure being 190 mmHg, and consciousness suddenly deteriorated on the 11th hospital day. Head fluid-attenuated inversion-recovery (FLAIR) MRI showed multiple lesions with high signal intensity, and she was diagnosed with PRES. After intravenous administration of nicardipine and fluid removal by hemodialysis, her blood pressure decreased and her consciousness dramatically improved. Conclusion: In addition to the vascular endothelial damage associated with vasculitis itself, steroid therapy, renal failure, elevated blood pressure, and administration of rituximab are related to an increased susceptibility of PRES. In particular, steroid administration increases blood pressure due to fluid retention and can be a risk factor for the development of PRES, suggesting the need for adequate fluid management during steroid administration.

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.

528: CEREBRAL BLOOD FLOW MONITORING PREDICTS RESPONSE TO INTRATHECAL NICARDIPINE TREATMENT FOR VASOSPASM

Introduction: A common complication of subarachnoid hemorrhage is cerebral vasospasm, which is associated with delayed cerebral ischemia, a predictor of poor functional outcome. Intrathecal administration of nicardipine upon detection of vasospasm holds promise as a treatment that reduces the incidence of secondary stroke. Herein, we utilize a novel non-invasive optical measurement of regional microvascular perfusion to determine the effect of intrathecal nicardipine on microvascular cerebral blood flow (CBF). Methods: In this observational study, we prospectively studied 20 patients with non-traumatic subarachnoid hemorrhage who required an external ventricular drain to treat obstructive hydrocephalus and who were treated with intrathecal nicardipine as part of usual care for evolving cerebral vasospasm. Regional microvascular CBF in the frontal cortex was measured with diffuse correlation spectroscopy for up to 90 min after the first treatment dose, and for a subset of patients, on days 2 and 3 of treatment as well. Outcome was assessed as the presence of delayed cerebral ischemia on imaging. Results: CBF increased significantly over the 90 min of monitoring after the first dose (p< 0.001) in the absence of systemic hemodynamic changes. CBF also increased on average in response to repeated doses on days 2 and 3, although the magnitude of this response decreased with successive treatment day. In general, the CBF response was heterogeneous across subjects. Using data from the first dose, a latent class mixture model was used to classify 19/20 patients into two distinct classes of cerebral blood flow response: patients in class 1 (n=6) showed a decrease or no change in CBF, while patients in class 2 (n=13) showed a pronounced increase in CBF in response to nicardipine. The incidence of delayed cerebral ischemia was 5/6 in class 1 and 0/13 in class 2 (p< 0.001). Similar significant differences in CBF response in patients with and without delayed cerebral ischemia were also observed on days 2 and 3 (both p< 0.001). Conclusions: These results suggest that the CBF response to intrathecal nicardipine reaches a therapeutic steady state with successive treatment days. Moreover, the CBF response may provide a valuable biomarker for treatment responsiveness.

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.

Intensive blood pressure lowering with nicardipine and outcomes after intracerebral hemorrhage: An individual participant data systematic review.

Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine after onset of intracerebral hemorrhage on clinical outcomes were determined. A systematic review and individual participant data analysis of articles before 1 October 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving hyperacute intracerebral hemorrhage adults 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 from baseline to 24-h computed tomography. Three studies met the eligibility criteria. For 1265 patients enrolled (age 62.6 ± 13.0 years, 484 women), death or disability occurred in 38.2% and hematoma expansion occurred in 17.4%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio (aOR) 1.12, 95% confidence interval (CI) 1.00-1.26 per 10 mmHg) and hematoma expansion (1.16, 1.02-1.32). Mean hourly systolic blood pressure from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Later achievement of systolic blood pressure to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00-1.05 per hour). Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability without increasing serious adverse events.

Opposing Responses of the Calcium Channel Blocker Nicardipine to Vascular Stiffness in the Elastic and Muscular Arteries in Rabbits.

Aim: The cardio-ankle vascular index (CAVI) consists of intrinsic and functional arterial stiffness mainly regulated by vasoactive compounds. A new stiffness index of the aorta (aBeta) and iliac-femoral arteries (ifBeta) was determined by applying the CAVI theory to the whole aorta and iliac-femoral arteries. We investigated the changes in aBeta and ifBeta in response to decreased blood pressure (BP) induced by the Ca 2＋ channel blocker nicardipine to elucidate the involvement of Ca 2＋ in aBeta and ifBeta. Methods: Pressure waves at the origin of the aorta (oA), distal end of the abdominal aorta (dA), and left femoral artery (fA) as well as flow waves at the oA were simultaneously recorded before and after the infusion of nicardipine (50 µg/kg/min) for 2 min in 12 male rabbits under pentobarbital anesthesia. Beta was calculated using the following formula: Beta=2ρ / PP×ln (SBP / DBP)×PWV 2 , where ρ, SBP, DBP, and PP denote blood density and systolic, diastolic, and pulse pressures, respectively. aBeta, ifBeta, and aortic-iliac-femoral Beta (aifBeta) were calculated using aPWV, ifPWV, and aifPWV, respectively. Results: SBP, mean arterial pressure (MAP), DBP, and total peripheral vascular resistance significantly decreased during the administration of nicardipine, whereas cardiac output significantly increased. aBeta and ifBeta significantly increased and decreased, respectively, whereas aifBeta did not change despite the decrease in BP. ifBeta and aBeta positively and negatively correlated with BP, respectively, whereas aifBeta did not correlate with SBP. Conclusions: There were contradictory arterial responses to nicardipine between the elastic and muscular arteries. Unknown vasoconstriction mechanisms that are not involved in Ca 2＋ influx may function in the aorta in response to decreased BP.

Intensive Blood Pressure Lowering With Nicardipine for Better Outcomes After Intracerebral Haemorrhage: A Systematic Review and Meta-Analysis of Individual Participant Data

Background: Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure (SBP) levels achieved with intravenous nicardipine immediately after onset of intracerebral haemorrhage (ICH) on clinical outcomes were determined. Methods: A systematic review and individual patient data analysis of articles before October 1, 2020 identified on PubMed were performed. Prospective studies involving hyperacute ICH adults treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale (mRS) were eligible. Outcomes included death or disability at 90 days, defined as an mRS score of 4-6, and haematoma expansion, defined as an increase ≥6 mL from baseline to 24-h computed tomography. Findings: Three studies met the eligibility criteria. Of 1,271 patients overall, 1,265 (age 62.6±13.0 years, 484 women) with available SBP data were included. Death or disability occurred in 38.2%, and haematoma expansion occurred in 17.4%. Mean hourly SBP during the initial 24 h was positively associated with death or disability [adjusted odds ratio (aOR) 1.12, 95% CI 1.00–1.26 per 10 mmHg] and haematoma expansion (1.16, 1.02–1.32). The association of SBP with death or disability was modified by race, baseline diastolic BP, and study population (higher SBP increased the risk in Asians, aOR 1.26, 95% CI 1.10–1.43). Mean hourly SBP from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Slower lowering of SBP to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00–1.05, per hour). Interpretation: Rapid lowering of SBP by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute ICH decreased early haematoma expansion and 90-day death or disability without increasing serious adverse events. Funding: Japan Agency for Medical Research and Development. Conflict of Interest: All of the following conflicts are outside the submitted work.Toyoda reports personal fees from Daiichi-Sankyo, Bayer Yakuhin, Bristol-Myers-Squibb (BMS), and Nippon Boehringer-Ingelheim (NBI). Ihara reports grants from Panasonic, Shimadzu Corporation, BMS, Otsuka Pharmaceutical, and personal fees from Daiichi-Sankyo, Eisai, and Bayer Yakuhin.Itabashi reports grants from Tohoku Fukushi University and NBI. Yamagami reports research grants from BMS; lecturer’s fees from Stryker, Terumo, Medtronic, Medico’s Hirata, Johnson and Johnson, Bayer, Daiichi-Sankyo, BMS, NBI, Takeda, and Otsuka Pharmaceutical; and membership of the advisory boards for Daiichi-Sankyo. Itabashi reports honoraria from Bayer, Eisai, BMS, Daiichi Sankyo, NBI, Takeda, Otsuka Pharmaceutical, Tanabe-Mitsubishi Parma, Pfizer, GE Healthcare Japan, Stryker, Medtronic, and Johnson and Johnson, and research support from Tohoku Fukushi University and NBI. Sakai reports grants from Daiichi-Sankyo, Jimro, Medtronic, Terumo, and honoraria from Asahi-Intec, Biomedical Solutions, Daiichi-Sankyo, Medtronic, and Stryker. Inoue reports personal fees from Daiichi-Sankyo, Bayer, BMS, and Medtronic. Minematsu reports personal fees and other from Bayer Yakuhin and AstraZeneca, personal fees from Otsuka Pharmaceutical, NBI, Mitsubishi Tanabe Pharma, BMS, Pfizer, Japan Stryker, Daiichi-Sankyo, Astellas Pharma, Nippon Chemiphar, and Fuji Film RI Pharma; and other (Advisory Board) from CSL Behring, Medico’s Hirata, EPS Corporation, HEALIOS K.K., and T-PEC Corporation. Koga reports honoraria from Bayer Yakuhin, Otsuka, Daiichi-Sankyo, and NBI, scientific advisory board from Ono, and research support from Takeda, Daiichi-Sankyo, NBI, and Shionogi.None of the other authors has any conflicts of interest to declare. Ethical Approval: The study design followed PRISMA guidelines for IPD systematic reviews. Ethical approval to perform the present IPD analysis was obtained from the site of the corresponding author. The study is registered with PROSPERO (CRD42020213857).

Double standards: why is pulse oximetry standard care, whereas tissue oximetry is not?

Why is pulse oximetry a standard monitor, whereas tissue oximeter is not? Is this a double-standard treatment? There appears to be a lack of enthusiasm for a continual investigation into whether the use of pulse oximetry leads to reduced morbidity and mortality in acute care although there is no robust evidence attesting to its outcome benefits. In contrast, research investigating the outcome effectiveness of tissue oximetry-guided care is consistently ongoing. A recent randomized controlled trial involving 800 patients who underwent laparoscopic hysterectomy found that, although muscular tissue oxygen saturation-guided care did not reduce the overall occurrence of postoperative nausea and vomiting for all patients, it did reduce the occurrence of these symptoms in patients who had a body mass index ≥25. It was also observed that muscular tissue oxygen saturation increases when blood pressure falls following the administration of nicardipine. These studies highlight the persistence of interest in understanding the value of tissue oximetry in patient care. Pulse oximetry and tissue oximetry are treated differently although neither monitor has robust evidence attesting to its outcome benefits. This difference may root in the difference in the physiology they monitor, the cost, the ease of use/interpretation/intervention and the relevance to patient safety and care quality. Pulse oxygen saturation represents a vital sign, whereas tissue oxygen saturation is likely a quality sign; however, further research endeavors are required to fully understand how to best use tissue oximetry.

Novel Imaging Revealing Inner Dynamics for Cardiovascular Waveform Analysis via Unsupervised Manifold Learning.

Cardiovascular waveforms contain information for clinical diagnosis. By learning and organizing the subtle change of waveform morphology from large amounts of raw waveform data, unsupervised manifold learning helps delineate a high-dimensional structure and display it as a novel 3-dimensional (3D) image. We hypothesize that the shape of this structure conveys clinically relevant inner dynamics information. To validate this hypothesis, we investigate the electrocardiography (ECG) waveform for ischemic heart disease and arterial blood pressure (ABP) waveform in dynamic vasoactive episodes. We model each beat or pulse to be a point lying on a manifold-like a surface-and use the diffusion map (DMap) to establish the relationship among those pulses. The output of the DMap is converted to a 3D image for visualization. For ECG datasets, first we analyzed the non-ST-elevation ECG waveform distribution from unstable angina to healthy control in the 3D image, and we investigated intraoperative ST-elevation ECG waveforms to show the dynamic ECG waveform changes. For ABP datasets, we analyzed waveforms collected under endotracheal intubation and administration of vasodilator. To quantify the dynamic separation, we applied the support vector machine (SVM) analysis and reported the total accuracy and macro-F1 score. We further performed the trajectory analysis and derived the moving direction of successive beats (or pulses) as vectors in the high-dimensional space. For the non-ST-elevation ECG, a hierarchical tree structure comprising consecutive ECG waveforms spanning from unstable angina to healthy control is presented in the 3D image (accuracy = 97.6%, macro-F1 = 96.1%). The DMap helps quantify and visualize the evolving direction of intraoperative ST-elevation myocardial episode in a 1-hour period (accuracy = 97.58%, macro-F1 = 96.06%). The ABP waveform analysis of Nicardipine administration shows interindividual difference (accuracy = 95.01%, macro-F1 = 96.9%) and their common directions from intraindividual moving trajectories. The dynamic change of the ABP waveform during endotracheal intubation shows a loop-like trajectory structure, which can be further divided using the manifold learning knowledge obtained from Nicardipine. The DMap and the generated 3D image of ECG or ABP waveforms provides clinically relevant inner dynamics information. It provides clues of acute coronary syndrome diagnosis, shows clinical course in myocardial ischemic episode, and reveals underneath physiological mechanism under stress or vasodilators.

Abstract WP399: Delayed Response to Intensive Blood Pressure Lowering and Poor Clinical Outcomes in Acute Intracerebral Hemorrhage

Background and purpose: We aimed to highlight temporal trajectories of systolic blood pressure (SBP) in patients with acute intracerebral hemorrhage (ICH) to investigate the clinical relevance of heterogeneity in responses to blood pressure lowering therapy. Methods: A post-hoc analysis of ATACH-2 trial, in which ICH patients were randomly assigned to intensive or standard SBP lowering with intravenous administration of nicardipine. Using data for all 1000 patients enrolled from 110 clinical sites, temporal changes of hourly maximum SBP up to 24 hours after randomization were analyzed with the group-based trajectory modeling (GBTM). Model selection was mainly based on the Bayesian Information Criteria. The primary outcome was death or disability (modified Rankin Scale score 4-6) at 3 months. Secondary outcomes included hematoma expansion within 24 hours and acute kidney injury (AKI). AKI was defined as an increase in serum creatinine by ≥0.3 mg/dl or to ≥1.5 times baseline within 48 hours. The outcomes were compared between the trajectory groups using multivariable logistic models with random-effects by clinical sites. Results: Of the analyzed 1000 patients, death or disability, hematoma expansion, and AKI were encountered in 367, 161, and 101 patients, respectively. GBTM revealed 4 SBP trajectory groups: early response-low SBP (38.2%), moderate SBP (16.8%), delayed response-low SBP (14.2%), and high SBP (30.8%). Nicardipine dosage was highest in the delayed response-low SBP group, 81.7% of which were from the intensive SBP lowering group. The risk of death or disability was higher only in the delayed response-low SBP group (adjusted odds ratio [aOR] 2.86; 95% confidence interval [CI] 1.66-4.93) than in the early response-low SBP group. The risk of hematoma expansion was not significantly different among the groups. The delayed response-low SBP group had higher risk of AKI (aOR 2.78; 95% CI 1.46-5.31; reference, the early response-low SBP group). Conclusions: An SBP trajectory group with delayed SBP lowering despite intensive treatment was associated with increased risk of death or disability at 3 months. Resistance to intensive SBP lowering may predict poor clinical outcomes, and intensive SBP control in these cases will increase the risk of AKI.

Clevidipine use after first-line treatment failure for perioperative hypertension in neurosurgical patients

Perioperative hypertension is a common occurrence in the neurosurgical population, where 60% to 90% of the patients require treatment for blood pressure (BP) control. Nicardipine and clevidipine have been commonly used in neurocritical settings. This retrospective, observational study assessed the effectivity of the administration of clevidipine after nicardipine treatment failure in neurosurgical patients.We retrospectively reviewed the medical charts of adult patients who were admitted to our neurosurgical department and received clevidipine after nicardipine treatment failure for the control of BP. The primary effectivity outcome was the comparison of the percentage of time spent at targeted SBP goals during nicardipine and clevidipine administration, respectively.A total of 12 adult patients treated with clevidipine after nicardipine treatment failure and were included for data analysis. The median number of events that required dose-titration was 20.5 vs 17 during the administration of nicardipine and clevidipine, respectively (P = .534). The median percentage of time spent at targeted SBP goal was 76.2% during the administration of nicardipine and 93.4% during the administration of clevidipine (P = .123).Our study suggests that clevidipine could be an alternative effective drug with an acceptable benefit/risk ratio in the neurosurgical population that fails to achieve BP control with nicardipine treatment.

Assessment of Cerebral Vasodilatory Capacity as Part of Catheter-Based Cerebral Angiography.

Cerebral vasodilatory capacity assessment for risk stratification in patients with extracranial arterial stenosis or occlusion may be useful. We describe a new method that assesses cerebral vasodilatory capacity as part of catheter-based cerebral angiography. We prospectively assessed regional cerebral blood volume (rCBV) in the arterial distribution of interest using a controlled contrast injection in the common carotid or the subclavian arteries. rCBV maps were created using a predefined algorithm based on contrast distribution in the venous phase (voxel size: .466 mm3 ). rCBV maps were acquired again after selective administration of intra-arterial nicardipine (2.0 mg) distal to the stenosis. Two independent observers graded the change in rCBV in 10 predefined anatomical regions within the tributaries of the artery of interest (0 = reduction, 1 = no change, 2 = increase) and total rCBV change scores were summated. Twenty-five patients with internal carotid artery stenosis (n = 18; 0-90% in severity) or extracranial vertebral artery stenosis (n = 7; 0-100% in severity) were assessed. There was an increase in rCBV in a tributary of the artery of interest in 18 of 25 after intra-arterial nicardipine (mean score: 11.98; range 0-19.5). There was no change or decrease in rCBV in 7 of 25 patients. The mean rCBV change score was similar in patients with an assessment of internal carotid artery or vertebral artery distributions (12.2 ± 5.3; 11.4 ± 2.5; P = .68). Selective vasodilatory response to intra-arterial nicardipine in the affected arterial distribution during catheter-based cerebral angiography may provide new data for risk stratification.

Abstract WP22: A New Technique for the Assessment of Cerebral Vasodilatory Capacity as Part of Catheter-Based Cerebral Angiography

Background: Cerebral vasodilatory capacity assessment for risk stratification in patients with extracranial arterial stenosis or occlusion may be useful. We describe a new method that assesses cerebral vasodilatory capacity as part of catheter-based cerebral angiography. Methods: We prospectively assessed regional cerebral blood volume (rCBV) in the arterial distribution of interest using a controlled contrast injection in the common carotid or the subclavian arteries. rCBV maps were created using a predefined algorithm based on contrast distribution in the venous phase (voxel size 0.466 mm 3 ). rCBV maps were acquired again after selective administration of intra-arterial nicardipine (2.5 mg) distal to the stenosis. Two independent observers graded the change in rCBV in 10 predefined anatomical regions within the tributaries of the artery of interest (0=reduction, 1=no change, 2=increase) and total rCBV change scores were summated. The rCBV score values were averaged between the two observers for each patient. Mean arterial pressure was monitored at baseline and at 1 minute intervals post nicardipine administration for 5 minutes. Results: Twenty-five patients with internal carotid artery stenosis (n=18; 0%-90% in severity) or extracranial vertebral artery stenosis (n=7; 0%-100% in severity) were assessed. There was an increase in rCBV in a tributary of the artery of interest in 18 of 25 after intra-arterial nicardipine (mean score 11.98; range 0-19.5). There was no change or decrease in rCBV in 7 of 25 patients. The mean rCBV change score was similar in patients with assessment of internal carotid artery or vertebral artery distributions (12.2 ± 5.3; 11.4 ± 2.5; p=0.68 by ANOVA). There was an average (±SD) reduction of mean arterial pressure of 14mmHg ± 7.5 after intra-arterial nicardipine. There was no correlation between the magnitude of mean arterial pressure reduction post nicardipine (regression coefficient -0.13; p=0.38) or between the severity of stenosis (regression coefficient -0.04; p=0.29) and rCBV change scores. Conclusions: We describe a new technique for selective assessment of cerebral vasodilatory response in the affected arterial distribution during catheter-based cerebral angiography.

Nicardipine Associated Risk of Short-Term Mortality in Critically Ill Patients with Ischemic Stroke

Background: Hypertensive emergency is commonly associated with acute ischemic stroke and can be a predictor of poor outcome in these patients. Nicardipine and labetalol are commonly administered for the treatment of acute hypertension following stroke. Yet, data are lacking on the safety of these agents in this setting. Objective: This study aimed to determine all-cause in-hospital mortality, medication-related hypotensive episodes, development of hospital acquired infections and hospital length of stay between nicardipine and labetalol use for the management of hypertension after acute ischemic stroke. Methods: This retrospective study used a prospective database of individuals admitted to the neurointensive care unit at a university-based hospital over 39 months. Patients with confirmed ischemic strokes were included in this analysis. Data were recorded for administration of nicardipine and labetalol following acute stroke. Results: A total of 244 patients with acute ischemic stroke were included in this analysis (mean age, 64.3 ± 15 years; 52.2% males). Nicardipine use after acute ischemic stroke was associated with an increased risk of 30-day mortality (odds ratio [OR]: 4.6, 95% confidence interval [CI] 1.3-15.7; P = .02). A single episode of hypotension in the first 72hours of admission was also significantly associated with mortality (OR 4.35 [95% CI 1.2-14.9]; P = .02). Conclusions: Nicardipine was associated with an increased risk of short-term mortality after acute ischemic stroke. This may have been due to hypotension, tachycardia, or pulmonary edema which were not apparent in our study. Further studies are required to elucidate the cause of this association.