Management of hypertensive emergencies in acute brain disease: evaluation of the treatment effects of intravenous nicardipine on cerebral oxygenation

Clinical article

Restricted access

Object

Inappropriate sudden blood pressure (BP) reductions may adversely affect cerebral perfusion. This study explores the effect of nicardipine on regional brain tissue O2 (PbtO2) during treatment of acute hypertensive emergencies.

Methods

A prospective case–control study was performed in 30 patients with neurological conditions and clinically elevated BP. All patients had a parenchymal PbtO2 and intracranial pressure bolt inserted following resuscitation. Using a critical care guide, PbtO2 was optimized. Intravenous nicardipine (5–15 mg/hour) was titrated to systolic BP < 160 mm Hg, diastolic BP < 90 mm Hg, mean arterial BP (MABP) 90–110 mm Hg, and PbtO2 > 20 mm Hg. Physiological parameters—intracranial pressure, PbtO2, central venous pressure, systolic BP, diastolic BP, MABP, fraction of inspired O2, and cerebral perfusion pressure (CPP)—were compared before infusion, at 4 hours, and at 8 hours using a t-test.

Results

Sixty episodes of hypertension were reported in 30 patients (traumatic brain injury in 13 patients; aneurysmal subarachnoid hemorrhage in 11; intracerebral and intraventricular hemorrhage in 3 and 1, respectively; arteriovenous malformation in 1; and hypoxic brain injury in 1). Nicardipine was effective in 87% of the patients (with intravenous β blockers in 4 patients), with a 19.7% reduction in mean 4-hour MABP (115.3 ± 13.1 mm Hg preinfusion vs 92.9 ± 11.40 mm Hg after 4 hours of therapy, p < 0.001). No deleterious effect on mean PbtO2 was recorded (26.74 ± 15.42 mm Hg preinfusion vs 27.68 ± 12.51 mm Hg after 4 hours of therapy, p = 0.883) despite significant reduction in CPP. Less dependence on normobaric hyperoxia was achieved at 8 hours (0.72 ± 0.289 mm Hg preinfusion vs 0.626 ± 0.286 mm Hg after 8 hours of therapy, p < 0.01). Subgroup analysis revealed that 12 patients had low pretreatment PbtO2 (10.30 ± 6.49 mm Hg), with higher CPP (p < 0.001) requiring hyperoxia (p = 0.02). In this group, intravenous nicardipine resulted in an 83% improvement in 4- and 8-hour PbtO2 levels (18.1 ± 11.33 and 19.59 ± 23.68 mm Hg, respectively; p < 0.01) despite significant reductions in both mean MABP (120.6 ± 16.65 vs 95.8 ± 8.3 mm Hg, p < 0.001) and CPP (105.00 ± 20.7 vs 81.2 ± 15.4 mm Hg, p < 0.001).

Conclusions

Intravenous nicardipine is effective for the treatment of hypertensive neurological emergencies and has no adverse effect on PbtO2.

Abbreviations used in this paper:ACVS = acute cerebrovascular syndrome; BP = blood pressure; CBF = cerebral blood flow; CPP = cerebral perfusion pressure; FiO2 = fraction of inspired O2,; ICH = intracerebral hemorrhage; ICP = intracranial pressure; MABP = mean arterial BP; PbtO2 = regional brain tissue O2; SAH = subarachnoid hemorrhage; TBI = traumatic brain injury.
Article Information

Contributor Notes

Address correspondence to: Pradeep K. Narotam, M.D., Union Hospital Neuroscience, 1530 N. 7th Street, #501, Terre Haute, Indiana 47807. email: narotam@mac.com.

© Copyright 1944-2019 American Association of Neurological Surgeons

Headings
References
  • 1

    Ahmed NNasman PWahlgren NG: Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke 31:125012552000

    • Search Google Scholar
    • Export Citation
  • 2

    Ahmed NWahlgren G: High initial blood pressure after acute stroke is associated with poor functional outcome. J Intern Med 249:4674732001

    • Search Google Scholar
    • Export Citation
  • 3

    Ahmed NWahlgren NG: Effects of blood pressure lowering in the acute phase of total anterior circulation infarcts and other stroke subtypes. Cerebrovasc Dis 15:2352432003

    • Search Google Scholar
    • Export Citation
  • 4

    Alabadí JASalom JBTorregrosa GMiranda FJJover TAlborch E: Changes in the cerebrovascular effects of endothelin-1 and nicardipine after experimental subarachnoid hemorrhage. Neurosurgery 33:7077151993

    • Search Google Scholar
    • Export Citation
  • 5

    Amenta FTomassoni D: Treatment with nicardipine protects brain in an animal model of hypertension-induced damage. Clin Exp Hypertens 26:3513612004

    • Search Google Scholar
    • Export Citation
  • 6

    Badjatia NTopcuoglu MAPryor JCRabinov JDOgilvy CSCarter BS: Preliminary experience with intra-arterial nicardipine as a treatment for cerebral vasospasm. AJNR Am J Neuroradiol 25:8198262004

    • Search Google Scholar
    • Export Citation
  • 7

    Bardt TFUnterberg AWHärtl RKiening KLSchneider GHLanksch WR: Monitoring of brain tissue PO2 in traumatic brain injury: effect of cerebral hypoxia on outcome. Acta Neurochir Suppl 71:1531561998

    • Search Google Scholar
    • Export Citation
  • 8

    Barth MCapelle HHWeidauer SWeiss CMunch EThome C: Effect of nicardipine prolonged-release implants on cerebral vasospasm and clinical outcome after severe aneurysmal subarachnoid hemorrhage: a prospective, randomized, double-blind phase IIa study. Stroke 38:3303362007

    • Search Google Scholar
    • Export Citation
  • 9

    Broderick JPAdams HP JrBarsan WFeinberg WFeldmann EGrotta J: Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 30:9059151999

    • Search Google Scholar
    • Export Citation
  • 10

    Cherney DStraus S: Management of patients with hypertensive urgencies and emergencies: a systematic review of the literature. J Gen Intern Med 17:9379452002

    • Search Google Scholar
    • Export Citation
  • 11

    Cheung ATGuvakov DVWeiss SJSavino JSSalgo ISMeng QC: Nicardipine intravenous bolus dosing for acutely decreasing arterial blood pressure during general anesthesia for cardiac operations: pharmacokinetics, pharmacodynamics, and associated effects on left ventricular function. Anesth Analg 89:111611231999

    • Search Google Scholar
    • Export Citation
  • 12

    Chobanian AVBakris GLBlack HRCushman WCGreen LAIzzo JL Jr: Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42:120612522003

    • Search Google Scholar
    • Export Citation
  • 13

    Compton JSLee TJones NRWaddell GTeddy PJ: A double blind placebo controlled trial of the calcium entry blocking drug, nicardipine, in the treatment of vasospasm following severe head injury. Br J Neurosurg 4:9151990

    • Search Google Scholar
    • Export Citation
  • 14

    Denolle TSassano PAllain HBentue-Ferrer DBreton SCimarosti I: Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients. Fundam Clin Pharmacol 16:5275352002

    • Search Google Scholar
    • Export Citation
  • 15

    Elliott WJ: Clinical features and management of selected hypertensive emergencies. J Clin Hypertens (Greenwich) 6:5875922004

  • 16

    Fandino JStocker RProkop STrentz OImhof HG: Cerebral oxygenation and systemic trauma related factors determining neurological outcome after brain injury. J Clin Neurosci 7:2262332000

    • Search Google Scholar
    • Export Citation
  • 17

    Filippi RReisch RMauer DPerneczky A: Brain tissue pO2 related to SjvO2, ICP, and CPP in severe brain injury. Neurosurg Rev 23:94972000

    • Search Google Scholar
    • Export Citation
  • 18

    Flamm ESAdams HP JrBeck DWPinto RSMarler JRWalker MD: Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 68:3934001988

    • Search Google Scholar
    • Export Citation
  • 19

    Fogelholm RAvikainen SMurros K: Prognostic value and determinants of first-day mean arterial pressure in spontaneous supratentorial intracerebral hemorrhage. Stroke 28:139614001997

    • Search Google Scholar
    • Export Citation
  • 20

    Gaab MRCzech TKorn A: Intracranial effects of nicardipine. Br J Clin Pharmacol 20:1 Suppl67S74S1985

  • 21

    Grotta JSpydell JPettigrew COstrow PHunter D: The effect of nicardipine on neuronal function following ischemia. Stroke 17:2132191986

    • Search Google Scholar
    • Export Citation
  • 22

    Haas CELeBlanc JM: Acute postoperative hypertension: a review of therapeutic options. Am J Health Syst Pharm 61:166116752004

  • 23

    Haitsma IKMaas AI: Advanced monitoring in the intensive care unit: brain tissue oxygen tension. Curr Opin Crit Care 8:1151202002

  • 24

    Haley EC JrKassell NFTorner JC: A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. J Neurosurg 78:5375471993

    • Search Google Scholar
    • Export Citation
  • 25

    Haley EC JrKassell NFTorner JC: A randomized trial of nicardipine in subarachnoid hemorrhage: angiographic and transcranial Doppler ultrasound results. A report of the Cooperative Aneurysm Study. J Neurosurg 78:5485531993

    • Search Google Scholar
    • Export Citation
  • 26

    Hemphill JCMorabito DFarrant MManley GT: Brain tissue oxygen monitoring in intracerebral hemorrhage. Neurocrit Care 3:2602702005

    • Search Google Scholar
    • Export Citation
  • 27

    Jarus-Dziedzic KCzernicki ZKozniewska E: Acute decrease of cerebrocortical microflow and lack of carbon dioxide reactivity following subarachnoid haemorrhage in the rat. Acta Neurochir Suppl 86:4734762003

    • Search Google Scholar
    • Export Citation
  • 28

    Kasuya HOnda HSasahara ATakeshita MHori T: Application of nicardipine prolonged-release implants: analysis of 97 consecutive patients with acute subarachnoid hemorrhage. Neurosurgery 56:8959022005

    • Search Google Scholar
    • Export Citation
  • 29

    Kasuya HOnda HTakeshita MOkada YHori T: Efficacy and safety of nicardipine prolonged-release implants for preventing vasospasm in humans. Stroke 33:101110152002

    • Search Google Scholar
    • Export Citation
  • 30

    Kiening KLHartl RUnterberg AWSchneider GHBardt TLanksch WR: Brain tissue pO2-monitoring in comatose patients: implications for therapy. Neurol Res 19:2332401997

    • Search Google Scholar
    • Export Citation
  • 31

    Kross RAFerri ELeung DPratila MBroad CVeronesi M: A comparative study between a calcium channel blocker (Nicardipine) and a combined alpha-beta-blocker (Labetalol) for the control of emergence hypertension during craniotomy for tumor surgery. Anesth Analg 91:9049092000

    • Search Google Scholar
    • Export Citation
  • 32

    Littlejohns LBader MK: Prevention of secondary brain injury: targeting technology. AACN Clin Issues 16:5015142005

  • 33

    Manley GKnudson MMMorabito DDamron SErickson VPitts L: Hypotension, hypoxia, and head injury: frequency, duration, and consequences. Arch Surg 136:111811232001

    • Search Google Scholar
    • Export Citation
  • 34

    Manley GTHemphill JCMorabito DDerugin NErickson VPitts LH: Cerebral oxygenation during hemorrhagic shock: perils of hyperventilation and the therapeutic potential of hypoventilation. J Trauma 48:102510332000

    • Search Google Scholar
    • Export Citation
  • 35

    Manley GTPitts LHMorabito DDoyle CAGibson JGimbel M: Brain tissue oxygenation during hemorrhagic shock, resuscitation, and alterations in ventilation. J Trauma 46:2612671999

    • Search Google Scholar
    • Export Citation
  • 36

    Marti Masso JFLozano R: Nicardipine in the prevention of cerebral infarction. Clin Ther 12:3443511990

  • 37

    Meixensberger JVath AJaeger MKunze EDings JRoosen K: Monitoring of brain tissue oxygenation following severe subarachnoid hemorrhage. Neurol Res 25:4454502003

    • Search Google Scholar
    • Export Citation
  • 38

    Narotam PKBurjonrappa SCRaynor SCRao MTaylon C: Cerebral oxygenation in major pediatric trauma: its relevance to trauma severity and outcome. J Pediatr Surg 41:5055132006

    • Search Google Scholar
    • Export Citation
  • 39

    Neutel JMSmith DHWallin DCook ERam CVFletcher E: A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension. Am J Hypertens 7:6236281994

    • Search Google Scholar
    • Export Citation
  • 40

    Patel HPMitsnefes M: Advances in the pathogenesis and management of hypertensive crisis. Curr Opin Pediatr 17:2102142005

  • 41

    Powers WJZazulia ARVideen TOAdams REYundt KDAiyagari V: Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage. Neurology 57:18242001

    • Search Google Scholar
    • Export Citation
  • 42

    Qureshi AIHarris-Lane PKirmani JFAhmed SJacob MZada Y: Treatment of acute hypertension in patients with intracerebral hemorrhage using American Heart Association guidelines. Crit Care Med 34:197519802006

    • Search Google Scholar
    • Export Citation
  • 43

    Qureshi AIMohammad YMYahia AMSuarez JISiddiqui AMKirmani JF: A prospective multicenter study to evaluate the feasibility and safety of aggressive antihypertensive treatment in patients with acute intracerebral hemorrhage. J Intensive Care Med 20:34422005

    • Search Google Scholar
    • Export Citation
  • 44

    Reinert MBarth ARothen HUSchaller BTakala JSeiler RW: Effects of cerebral perfusion pressure and increased fraction of inspired oxygen on brain tissue oxygen, lactate and glucose in patients with severe head injury. Acta Neurochir (Wien) 145:3413502003

    • Search Google Scholar
    • Export Citation
  • 45

    Ribas Mundo MLozano R: The influence of nicardipine in patients with high risk of stroke. J Cardiovasc Pharmacol 16:2 SupplS16S191990

    • Search Google Scholar
    • Export Citation
  • 46

    Rinkel GJFeigin VLAlgra AVermeulen Mvan Gijn J: Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 4:CD0002772002

    • Search Google Scholar
    • Export Citation
  • 47

    Robertson CSValadka ABHannay HJContant CFGopinath SPCormio M: Prevention of secondary ischemic insults after severe head injury. Crit Care Med 27:208620951999

    • Search Google Scholar
    • Export Citation
  • 48

    Rose JCMayer SA: Optimizing blood pressure in neurological emergencies. Neurocrit Care 1:2872992004

  • 49

    Rosenbaum DZabramski JFrey JYatsu FMarler JSpetzler R: Early treatment of ischemic stroke with a calcium antagonist. Stroke 22:4374411991

    • Search Google Scholar
    • Export Citation
  • 50

    Rosenbaum DMGrotta JCYatsu FMPicone CMPettigrew LCBratina P: Pilot study of nicardipine for acute ischemic stroke. Angiology 41:101710221990

    • Search Google Scholar
    • Export Citation
  • 51

    Sahuquillo JAmoros SSantos APoca MAPanzardo HDominguez L: Does an increase in cerebral perfusion pressure always mean a better oxygenated brain? A study in head-injured patients. Acta Neurochir Suppl 76:4574622000

    • Search Google Scholar
    • Export Citation
  • 52

    Sahuquillo JRobles APoca ABallabriga AMercadal JSecades JJ: [A controlled, double-blind, randomized pilot clinical trial of nicardipine as compared with a placebo in patients with moderate or severe head injury.]. Rev Neurol 30:4014082000. (Fr)

    • Search Google Scholar
    • Export Citation
  • 53

    Sarrafzadeh ASKiening KLBardt TFSchneider GHUnterberg AWLanksch WR: Cerebral oxygenation in contusioned vs. nonlesioned brain tissue: monitoring of PtiO2 with Licox and Paratrend. Acta Neurochir Suppl 71:1861891998

    • Search Google Scholar
    • Export Citation
  • 54

    Singh BNJosephson MA: Clinical pharmacology, pharmacokinetics, and hemodynamic effects of nicardipine. Am Heart J 119:4274341990

  • 55

    Stevens WJ: Multimodal monitoring: head injury management using SjvO2 and LICOX. J Neurosci Nurs 36:3323392004

  • 56

    Stiefel MFHeuer GGAbrahams JMBloom SSmith MJMaloney-Wilensky E: The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage. J Neurosurg 101:5945992004

    • Search Google Scholar
    • Export Citation
  • 57

    Stiefel MFSpiotta AGracias VHGaruffe AMGuillamondegui OMaloney-Wilensky E: Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring. J Neurosurg 103:8058112005

    • Search Google Scholar
    • Export Citation
  • 58

    Stiefel MFUdoetuk JDSpiotta AMGracias VHGoldberg AMaloney-Wilensky E: Conventional neurocritical care and cerebral oxygenation after traumatic brain injury. J Neurosurg 105:5685752006

    • Search Google Scholar
    • Export Citation
  • 59

    Tuncel MRam VC: Hypertensive emergencies. Etiology and management. Am J Cardiovasc Drugs 3:21312003

  • 60

    Unterberg AWKiening KLHartl RBardt TSarrafzadeh ASLanksch WR: Multimodal monitoring in patients with head injury: evaluation of the effects of treatment on cerebral oxygenation. J Trauma 42:S32S371997

    • Search Google Scholar
    • Export Citation
  • 61

    van den Brink WAvan Santbrink HAvezaat CJHogesteeger CJansen WKloos LM: Monitoring brain oxygen tension in severe head injury: the Rotterdam experience. Acta Neurochir Suppl 71:1901941998

    • Search Google Scholar
    • Export Citation
  • 62

    van den Brink WAvan Santbrink HSteyerberg EWAvezaat CJSuazo JAHogesteeger C: Brain oxygen tension in severe head injury. Neurosurgery 46:8688782000

    • Search Google Scholar
    • Export Citation
  • 63

    van Santbrink HMaas AIAvezaat CJ: Continuous monitoring of partial pressure of brain tissue oxygen in patients with severe head injury. Neurosurgery 38:21311996

    • Search Google Scholar
    • Export Citation
  • 64

    van Santbrink Hvan den Brink WASteyerberg EWCarmona Suazo JAAvezaat CJMaas AI: Brain tissue oxygen response in severe traumatic brain injury. Acta Neurochir (Wien) 145:4294382003

    • Search Google Scholar
    • Export Citation
  • 65

    Vaughan CJDelanty N: Hypertensive emergencies. Lancet 356:4114172000

  • 66

    Wallin JDFletcher ERam CVCook MECheung DGMacCarthy EP: Intravenous nicardipine for the treatment of severe hypertension. A double-blind, placebo-controlled multicenter trial. Arch Intern Med 149:266226691989

    • Search Google Scholar
    • Export Citation
  • 67

    Yang HJKim JGLim YSRyoo EHyun SYLee G: Nicardipine versus nitroprusside infusion as antihypertensive therapy in hypertensive emergencies. J Int Med Res 32:1181232004

    • Search Google Scholar
    • Export Citation
TrendMD
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 307 297 25
Full Text Views 242 147 2
PDF Downloads 98 53 2
EPUB Downloads 0 0 0
PubMed
Google Scholar