Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension

Clinical article

Restricted access

Object

Deepening sedation is often needed in patients with intracranial hypertension. All widely used sedative and anesthetic agents (opioids, benzodiazepines, propofol, and barbiturates) decrease blood pressure and may therefore decrease cerebral perfusion pressure (CPP). Ketamine is a potent, safe, rapid-onset anesthetic agent that does not decrease blood pressure. However, ketamine's use in patients with traumatic brain injury and intracranial hypertension is precluded because it is widely stated that it increases intracranial pressure (ICP). Based on anecdotal clinical experience, the authors hypothesized that ketamine does not increase—but may rather decrease—ICP.

Methods

The authors conducted a prospective, controlled, clinical trial of data obtained in a pediatric intensive care unit of a regional trauma center. All patients were sedated and mechanically ventilated prior to inclusion in the study. Children with sustained, elevated ICP (> 18 mm Hg) resistant to first-tier therapies received a single ketamine dose (1–1.5 mg/kg) either to prevent further ICP increase during a potentially distressing intervention (Group 1) or as an additional measure to lower ICP (Group 2). Hemodynamic, ICP, and CPP values were recorded before ketamine administration, and repeated-measures analysis of variance was used to compare these values with those recorded every minute for 10 minutes following ketamine administration.

Results

The results of 82 ketamine administrations in 30 patients were analyzed. Overall, following ketamine administration, ICP decreased by 30% (from 25.8 ± 8.4 to 18.0 ± 8.5 mm Hg) (p < 0.001) and CPP increased from 54.4 ± 11.7 to 58.3 ± 13.4 mm Hg (p < 0.005). In Group 1, ICP decreased significantly following ketamine administration and increased by > 2 mm Hg during the distressing intervention in only 1 of 17 events. In Group 2, when ketamine was administered to lower persistent intracranial hypertension, ICP decreased by 33% (from 26.0 ± 9.1 to 17.5 ± 9.1 mm Hg) (p < 0.0001) following ketamine administration.

Conclusions

In ventilation-treated patients with intracranial hypertension, ketamine effectively decreased ICP and prevented untoward ICP elevations during potentially distressing interventions, without lowering blood pressure and CPP. These results refute the notion that ketamine increases ICP. Ketamine is a safe and effective drug for patients with traumatic brain injury and intracranial hypertension, and it can possibly be used safely in trauma emergency situations.

Abbreviations used in this paper: ANOVA = analysis of variance; CBF = cerebral blood flow; CPP = cerebral perfusion pressure; ICP = intracranial pressure; MABP = mean arterial blood pressure; PICU = pediatric intensive care unit; TBI = traumatic brain injury.

Article Information

Address correspondence to: Gad Bar-Joseph, M.D., Pediatric Critical Care, Rambam Medical Center, P.O.B 9602, Haifa, Israel. email: g_barjoseph@rambam.health.gov.il.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Graphs showing ICP (A), CPP (B), and MABP (C; MAP) responses to ketamine administration in the entire study population (30 patients, 82 events). Intracranial pressure decreased by 30% within 2 minutes of ketamine administration. **p < 0.005, ***p < 0.001.

  • View in gallery

    Graphs demonstrating ICP (A), CPP (B), and MABP (C) responses to ketamine administration before a potentially distressing intervention in patients with intracranial hypertension (17 events, Group 1). Intracranial pressure decreased by ~ 20% within 2 minutes of ketamine administration and did not increase during the intervention. **p < 0.005, ***p < 0.001.

  • View in gallery

    Graphs showing ICP (A), CPP (B), and MABP (C) responses to ketamine administration in an attempt to lower markedly elevated ICP (65 events, Group 2). Intracranial pressure decreased by 33% within 2 minutes of ketamine administration. *p < 0.05, ***p < 0.0001.

References

  • 1

    Adelson PDBratton SLCarney NAChestnut RMdu Coudray HEGoldstein B: Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 9. Use of sedation and neuromuscular blockade in the treatment of severe pediatric traumatic brain injury. Pediatr Crit Care Med 4:3 SupplS34 S372003

    • Search Google Scholar
    • Export Citation
  • 2

    Adelson PDBratton SLCarney NAChestnut RMdu Coudray HEGoldstein B: Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 17. Critical pathway for the treatment of established intracranial hypertension in pediatric traumatic brain injury. Pediatr Crit Care Med 4:3 SupplS65S672003

    • Search Google Scholar
    • Export Citation
  • 3

    Åkeson JBjörkman SMesseter KRosen I: Low-dose midazolam antagonizes cerebral metabolic stimulation by ketamine in the pig. Acta Anaesthesiol Scand 37:5255311993

    • Search Google Scholar
    • Export Citation
  • 4

    Åkeson JBjörkman SMesseter KRosen IHelfer M: Cerebral pharmacodynamics of anaesthetic and subanaesthetic doses of ketamine in the normoventilated pig. Acta Anaesthesiol Scand 37:2112181993

    • Search Google Scholar
    • Export Citation
  • 5

    Albanèse JArnaud SRey MThomachot LAlliez BMartin C: Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation. Anesthesiology 87:132813341997

    • Search Google Scholar
    • Export Citation
  • 6

    Belopavlovic MBuchthal A: Modification of ketamine-induced intracranial hypertension in neurosurgical patients by pretreatment with midazolam. Acta Anaesthesiol Scand 26:4584621982

    • Search Google Scholar
    • Export Citation
  • 7

    Björkman SÅkeson JNilsson FMesseter KRoth B: Ketamine and midazolam decrease cerebral blood flow and consequently their own rate of transport to the brain: an application of mass balance pharmacokinetics with a changing regional blood flow. J Pharmacokinet Biopharm 20:637 6521992

    • Search Google Scholar
    • Export Citation
  • 8

    Bourgoin AAlbanèse JWereszczynski NCharbit MVialet RMartin C: Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil. Crit Care Med 31:7117172003

    • Search Google Scholar
    • Export Citation
  • 9

    Bratton SLChestnut RMGhajar JMcConnell Hammond FFHarris OAHartl R: Guidelines for the management of severe traumatic brain injury. XI. Anesthetics, analgesics, and sedatives. J Neurotrauma 24:Suppl 1S71S762007

    • Search Google Scholar
    • Export Citation
  • 10

    Craven R: Ketamine. Anaesthesia 62:Suppl 148532007

  • 11

    Crumrine RSNulsen FEWeiss MH: Alterations in ventricular fluid pressure during ketamine anesthesia in hydrocephalic children. Anesthesiology 42:7587611975

    • Search Google Scholar
    • Export Citation
  • 12

    Dawson BMichenfelder JDTheye RA: Effects of ketamine on canine cerebral blood flow and metabolism: modification by prior administration of thiopental. Anesth Analg 50:443 4471971

    • Search Google Scholar
    • Export Citation
  • 13

    Dershwitz MRosow CEPharmacology of intravenous anesthetics. Longnecker DEBrown DLNewman MF: Anesthesiology New YorkMcGraw-Hill2008. 849868

    • Search Google Scholar
    • Export Citation
  • 14

    Duke JCAnesthesia. Moore EEFeliciano DVMattox KL: Trauma ed 5New YorkMcGraw-Hill2003. 329354

  • 15

    Evans JRosen MWeeks RDWise C: Ketamine in neurosurgical procedures. Lancet 1:40411971

  • 16

    Evers ASCrowder CMBalser JRGeneral anesthetics. Brunton LLLazo JSParker KL: Goodman and Gilman's The Pharmacological Basis of Therapeutics ed 11New YorkMcGraw-Hill2006. 341368

    • Search Google Scholar
    • Export Citation
  • 17

    Gardner AEDannemiller FJDean D: Intracranial cerebrospinal fluid pressure in man during ketamine anesthesia. Anesth Analg 51:7417451972

    • Search Google Scholar
    • Export Citation
  • 18

    Gibbs JM: The effect of intravenous ketamine on cerebrospinal fluid pressure. Br J Anaesth 44:129813011972

  • 19

    Heard CMBFletcher JESedation and analgesia. Fuhrman BPZimmerman JJ: Pediatric Critical Care ed 3PhiladelphiaMosby-Elsevier2006. 17481779

    • Search Google Scholar
    • Export Citation
  • 20

    Holcomb HHLahti ACMedoff DRWeiler MTamminga CA: Sequential regional cerebral blood flow brain scans using PET with H215O demonstrate ketamine actions in CNS dynamically. Neuropsychopharmacology 25:1651722001

    • Search Google Scholar
    • Export Citation
  • 21

    Johnston MNLiebelt ELAcute pain management and procedural sedation in children. Tintinalli JEKelen GDStapczynski JS: Emergency Medicine: A Comprehensive Study Guide ed 6New YorkMcGraw-Hill2003. 858868

    • Search Google Scholar
    • Export Citation
  • 22

    Kolenda HGremmelt ARading SBraun UMarkakis E: Ketamine for analgosedative therapy in intensive care treatment of head-injured patients. Acta Neurochir (Wien) 138:1193 11991996

    • Search Google Scholar
    • Export Citation
  • 23

    Långsjö JWKaisti KKAalto SHinkka SAantaa ROikonen V: Effects of subanesthetic doses of ketamine on regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology 99:6146232003

    • Search Google Scholar
    • Export Citation
  • 24

    Lee TSChen BJIntensive care anesthesia and analgesia. Bongard FSSue DY: Current Critical Care Diagnosis and Treatment ed 2New YorkMcGraw-Hill2002. 104125

    • Search Google Scholar
    • Export Citation
  • 25

    List WFCrumrine RSCascorbi HFWeiss MH: Increased cerebrospinal fluid pressure after ketamine. Anesthesiology 36:98991972

  • 26

    Mayberg TSLam AMMatta BFDomino KBWinn HR: Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy. Anesth Analg 81:84 891995

    • Search Google Scholar
    • Export Citation
  • 27

    Oren RERasool NARubinstein EH: Effect of ketamine on cerebral cortical blood flow and metabolism in rabbits. Stroke 18:4414441987

    • Search Google Scholar
    • Export Citation
  • 28

    Ralston CSIntroduction to pediatric neurosurgery: physiologic and anesthetic considerations. Choux MDi Rocco CHockley AD: Pediatric Neurosurgery LondonChurchill Livingstone1999. 129

    • Search Google Scholar
    • Export Citation
  • 29

    Reves JGGlass PSALubarsky DAMcEvoy MDIntravenous nonopioid anesthetics. Miller RD: Miller's Anesthesia ed 6PhiladelphiaElsevier Churchill Livingstone2005. 317378

    • Search Google Scholar
    • Export Citation
  • 30

    Schulte am Esch JPfeifer GThiemig IEntzian W: The influence of intravenous anaesthetic agents on primarily increased intracranial pressure. Acta Neurochir (Wien) 45:15251978

    • Search Google Scholar
    • Export Citation
  • 31

    Schwedler MMiletich DJAlbrecht RF: Cerebral blood flow and metabolism following ketamine administration. Can Anaesth Soc J 29:2222261982

    • Search Google Scholar
    • Export Citation
  • 32

    Sehdev RSSymmons DAKindl K: Ketamine for rapid sequence induction in patients with head injury in the emergency department. Emerg Med Australas 18:37442006

    • Search Google Scholar
    • Export Citation
  • 33

    Shaprio HMWyte SRHarris AB: Ketamine anaesthesia in patients with intracranial pathology. Br J Anaesth 44:1200 12041972

  • 34

    Sherwood ERWilliams CGPrough DSAnesthesiology principles, pain management, and conscious sedation. Townsend CM JrBeauchamp RDEvers MB: Sabiston Textbook of Surgery ed 18PhiladelphiaSaunders2008. 401443

    • Search Google Scholar
    • Export Citation
  • 35

    Takeshita HOkuda YSari A: The effects of ketamine on cerebral circulation and metabolism in man. Anesthesiology 36:69751972

  • 36

    Trevor AJWhite PFGeneral anesthetics. Katzung BG: Basic and Clinical Pharmacology ed 10New YorkMcGraw-Hill, Lange2006. 395411

    • Search Google Scholar
    • Export Citation
  • 37

    Vishteh AGRaudzens PSpetzler RFTheodore NAnesthesia in cerebrovascular disease. Winn HR: Youmans Neurological Surgery ed 5PhiladelphiaWB Saunders2004. 15031514

    • Search Google Scholar
    • Export Citation
  • 38

    Wyte SRShapiro HMTurner P: Ketamine-induced intracranial hypertension. Anesthesiology 36:1741761972

  • 39

    Zimmer GDAcute pain management in the adult patient. Tintinalli JEKelen GDStapczynski JS: Emergency Medicine ed 6New YorkMcGraw-Hill2003. 257263

    • Search Google Scholar
    • Export Citation

TrendMD

Cited By

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 485 485 81
Full Text Views 179 179 14
PDF Downloads 273 273 11
EPUB Downloads 0 0 0

PubMed

Google Scholar