Skip to main content
Top
Published in: Journal of Anesthesia 6/2014

01-12-2014 | Original Article

Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized controlled trials

Authors: Xin Wang, Xibing Ding, Yao Tong, Jiaying Zong, Xiang Zhao, Hao Ren, Quan Li

Published in: Journal of Anesthesia | Issue 6/2014

Login to get access

Abstract

Background

Ketamine is traditionally avoided in sedation management of patients with risk of intracranial hypertension. However, results from many clinical trials contradict this concern. We critically analyzed the published data of the effects of ketamine on intracranial pressure (ICP) and other cerebral hemodynamics to determine whether ketamine was safe for patients with hemodynamic instability and brain injuries.

Methods

We systematically searched the online databases of PubMed, Medline, Embase, Current Controlled Trials, and Cochrane Central (last search performed on January 15, 2014). Trial characteristics and outcomes were independently extracted by two assessors (Xin Wang, Xibing Ding). For continuous data, mean differences (MD) were formulated. If the P value of the chi-square test was >0.10 or I 2 <50 %, a fixed-effects model was used; otherwise, the random effects model was adopted.

Results

Five trials (n = 198) met the inclusion criteria. Using ICP levels within the first 24 h of ketamine administration as the main outcome, the use of ketamine leads to the same ICP levels as opioids [MD = 1.94; 95 % confidence interval (95 % CI), −2.35, 6.23; P = 0.38]. There were no significant differences in mean arterial pressure values between the two groups (MD = 0.99; 95 % CI, −2.24, 4.22; P = 0.55). Ketamine administration was also comparable with opioids in the maintenance of cerebral perfusion pressure (MD = −1.07; 95 % CI, −7.95, 5.8; P = 0.76).

Conclusions

The results of this study suggest that ketamine does not increase ICP compared with opioids. Ketamine provides good maintenance of hemodynamic status. Clinical application of ketamine should not be discouraged on the basis of ICP-related concerns.
Literature
1.
go back to reference Chang LC, Raty SR, Ortiz J, Bailard NS, Mathew SJ. The emerging use of ketamine for anesthesia and sedation in traumatic brain injuries. CNS Neurosci Ther. 2013;19:390–5.PubMedCentralPubMedCrossRef Chang LC, Raty SR, Ortiz J, Bailard NS, Mathew SJ. The emerging use of ketamine for anesthesia and sedation in traumatic brain injuries. CNS Neurosci Ther. 2013;19:390–5.PubMedCentralPubMedCrossRef
3.
go back to reference Matta B, Menon D. Severe head injury in the United Kingdom and Ireland: a survey of practice and implications for management. Crit Care Med. 1996;24:1743–8.PubMedCrossRef Matta B, Menon D. Severe head injury in the United Kingdom and Ireland: a survey of practice and implications for management. Crit Care Med. 1996;24:1743–8.PubMedCrossRef
4.
go back to reference Mirski MA, Muffelman B, Ulatowski JA, Hanley DF. Sedation for the critically ill neurologic patient. Crit Care Med. 1995;23:2038–53.PubMedCrossRef Mirski MA, Muffelman B, Ulatowski JA, Hanley DF. Sedation for the critically ill neurologic patient. Crit Care Med. 1995;23:2038–53.PubMedCrossRef
5.
go back to reference Urwin SC, Menon DK. Comparative tolerability of sedative agents in head-injured adults. Drug Saf. 2004;27:107–33.PubMedCrossRef Urwin SC, Menon DK. Comparative tolerability of sedative agents in head-injured adults. Drug Saf. 2004;27:107–33.PubMedCrossRef
6.
go back to reference Rangel-Castilla L, Gopinath S, Robertson CS. Management of intracranial hypertension. Neurol Clin. 2008;26:521–41.PubMedCrossRef Rangel-Castilla L, Gopinath S, Robertson CS. Management of intracranial hypertension. Neurol Clin. 2008;26:521–41.PubMedCrossRef
7.
go back to reference Flower O, Hellings S. Sedation in traumatic brain injury. Emerg Med Int. 2012;10:1155–66. Flower O, Hellings S. Sedation in traumatic brain injury. Emerg Med Int. 2012;10:1155–66.
8.
go back to reference Roberts DJ, Hall RI, Kramer AH, Robertson HL, Gallagher CN, Zygun DA. Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials. Crit Care Med. 2011;39:2743–51.PubMedCrossRef Roberts DJ, Hall RI, Kramer AH, Robertson HL, Gallagher CN, Zygun DA. Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials. Crit Care Med. 2011;39:2743–51.PubMedCrossRef
9.
go back to reference Bowies ED, Gold ME. Rethinking the paradigm: evaluation of ketamine as a neurosurgical anesthetic. AANA J. 2012;80:445–52. Bowies ED, Gold ME. Rethinking the paradigm: evaluation of ketamine as a neurosurgical anesthetic. AANA J. 2012;80:445–52.
10.
go back to reference Caricato A, Tersali A, Pitoni S, De Waure C, Sandroni C, Bocci MG, Annetta MG, Pennisi MA, Antonelli M. Racemic ketamine in adult head injury patients: use in endotracheal suctioning. Crit Care. 2013;17(6):R267.PubMedCentralPubMedCrossRef Caricato A, Tersali A, Pitoni S, De Waure C, Sandroni C, Bocci MG, Annetta MG, Pennisi MA, Antonelli M. Racemic ketamine in adult head injury patients: use in endotracheal suctioning. Crit Care. 2013;17(6):R267.PubMedCentralPubMedCrossRef
11.
go back to reference Filanovsky Y, Miller P, Kao J. Myth: Ketamine should not be used as an induction agent for intubation in patients with head injury. Can J Emerg Med. 2010;12:154–201. Filanovsky Y, Miller P, Kao J. Myth: Ketamine should not be used as an induction agent for intubation in patients with head injury. Can J Emerg Med. 2010;12:154–201.
12.
go back to reference Gibbs JM. The effect of intravenous ketamine on cerebrospinal fluid pressure. Br J Anaesth. 1972;44:1298–302.PubMedCrossRef Gibbs JM. The effect of intravenous ketamine on cerebrospinal fluid pressure. Br J Anaesth. 1972;44:1298–302.PubMedCrossRef
13.
14.
go back to reference Shaprio HM, Wyte SR, Harris AB. Ketamine anaesthesia in patients with intracranial pathology. Br J Anaesth. 1972;44:1200–4.PubMedCrossRef Shaprio HM, Wyte SR, Harris AB. Ketamine anaesthesia in patients with intracranial pathology. Br J Anaesth. 1972;44:1200–4.PubMedCrossRef
15.
go back to reference Michalczyk K, Sullivan JE, Berkenbosch JW. Pretreatment with midazolam blunts the rise in intracranial pressure associated with ketamine sedation for lumbar puncture in children. Pediatr Crit Care Med. 2013;10:149–55.CrossRef Michalczyk K, Sullivan JE, Berkenbosch JW. Pretreatment with midazolam blunts the rise in intracranial pressure associated with ketamine sedation for lumbar puncture in children. Pediatr Crit Care Med. 2013;10:149–55.CrossRef
16.
go back to reference Bar-Joseph G, Guilburd Y, Tamir A, Guilburd JN. Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension. J Neurosurg Pediatr. 2009;4:40–6.PubMedCrossRef Bar-Joseph G, Guilburd Y, Tamir A, Guilburd JN. Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension. J Neurosurg Pediatr. 2009;4:40–6.PubMedCrossRef
17.
go back to reference Mayberg TS, Lam AM, Matta BF, Domino KB, Winn HR. Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy. Anesth Analg. 1995;81:84–9.PubMed Mayberg TS, Lam AM, Matta BF, Domino KB, Winn HR. Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy. Anesth Analg. 1995;81:84–9.PubMed
18.
go back to reference Albanèse J, Arnaud S, Rey M, Thomachot L, Alliez B, Martin C. Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation. Anesthesiology. 1997;87:1328–34.PubMedCrossRef Albanèse J, Arnaud S, Rey M, Thomachot L, Alliez B, Martin C. Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation. Anesthesiology. 1997;87:1328–34.PubMedCrossRef
19.
go back to reference Bourgoin A, Albanèse J, Wereszczynski N, Charbit M, Vialet R, Martin C. Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil. Crit Care Med. 2003;31:711–7.PubMedCrossRef Bourgoin A, Albanèse J, Wereszczynski N, Charbit M, Vialet R, Martin C. Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil. Crit Care Med. 2003;31:711–7.PubMedCrossRef
20.
go back to reference Bourgoin A, Albanèse J, Léone M, Sampol-Manos E, Viviand X, Martin C. Effects of sufentanil or ketamine administered in target-controlled infusion on the cerebral hemodynamics of severely brain-injured patients. Crit Care Med. 2005;33:1109–13.PubMedCrossRef Bourgoin A, Albanèse J, Léone M, Sampol-Manos E, Viviand X, Martin C. Effects of sufentanil or ketamine administered in target-controlled infusion on the cerebral hemodynamics of severely brain-injured patients. Crit Care Med. 2005;33:1109–13.PubMedCrossRef
21.
go back to reference Sehdev RS, Symmons DA, Kindl K. Ketamine for rapid sequence induction in patients with head injury in the emergency department. Emerg Med Australas. 2006;18:37–44.PubMedCrossRef Sehdev RS, Symmons DA, Kindl K. Ketamine for rapid sequence induction in patients with head injury in the emergency department. Emerg Med Australas. 2006;18:37–44.PubMedCrossRef
22.
go back to reference Himmelseher S, Durieux ME. Revising a dogma: ketamine for patients with neurological injury? Anesth Analg. 2005;101:524–34.PubMedCrossRef Himmelseher S, Durieux ME. Revising a dogma: ketamine for patients with neurological injury? Anesth Analg. 2005;101:524–34.PubMedCrossRef
23.
go back to reference Higgins JPT. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. Br Med J. 2011;343:d5928.CrossRef Higgins JPT. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. Br Med J. 2011;343:d5928.CrossRef
24.
go back to reference Schmittner MD, Vajkoczy SL, Horn P, Bertsch T, Quintel M, Vajkoczy P, Muench E. Effects of fentanyl and S(+)-ketamine on cerebral hemodynamics, gastrointestinal motility, and need of vasopressors in patients with intracranial pathologies. J Neurosurg Anesthesiol. 2007;19:257–62.PubMedCrossRef Schmittner MD, Vajkoczy SL, Horn P, Bertsch T, Quintel M, Vajkoczy P, Muench E. Effects of fentanyl and S(+)-ketamine on cerebral hemodynamics, gastrointestinal motility, and need of vasopressors in patients with intracranial pathologies. J Neurosurg Anesthesiol. 2007;19:257–62.PubMedCrossRef
25.
go back to reference Kolenda H, Gremmelt A, Rading S, Braun U, Markakis E. Ketamine for analgosedative therapy in intensive care treatment of head injured patients. Acta Neurochir (Wien). 1996;138:1193–9.CrossRef Kolenda H, Gremmelt A, Rading S, Braun U, Markakis E. Ketamine for analgosedative therapy in intensive care treatment of head injured patients. Acta Neurochir (Wien). 1996;138:1193–9.CrossRef
26.
go back to reference Schulte am Esch J, Pfeifer G, Thiemig I, Entzian W. The influence of intravenous anaesthetic agents on primarily increased intracranial pressure. Acta Neurochir. 1978;45:15–25.PubMedCrossRef Schulte am Esch J, Pfeifer G, Thiemig I, Entzian W. The influence of intravenous anaesthetic agents on primarily increased intracranial pressure. Acta Neurochir. 1978;45:15–25.PubMedCrossRef
27.
go back to reference Belopavlovic M, Buchthal A. Modification of ketamine-induced intracranial hypertension in neurosurgical patients by pretreatment with midazolam. Acta Anaesth Scand. 1982;26:458–62.PubMedCrossRef Belopavlovic M, Buchthal A. Modification of ketamine-induced intracranial hypertension in neurosurgical patients by pretreatment with midazolam. Acta Anaesth Scand. 1982;26:458–62.PubMedCrossRef
28.
go back to reference Mennella F, Bracali AM, Schiavello R. Effects of ketamine on cerebrospinal fluid pressure in cases with normotensive hydrocephalus. Minerva Anestesiol. 1976;42(6):418–20.PubMed Mennella F, Bracali AM, Schiavello R. Effects of ketamine on cerebrospinal fluid pressure in cases with normotensive hydrocephalus. Minerva Anestesiol. 1976;42(6):418–20.PubMed
29.
go back to reference Kaul HL, Jayalaxmi T, Gode GR, Mitra DK. Effect of ketamine on intracranial pressure in hydrocephalic children. Anaesthesia. 1976;31(5):698–701.PubMedCrossRef Kaul HL, Jayalaxmi T, Gode GR, Mitra DK. Effect of ketamine on intracranial pressure in hydrocephalic children. Anaesthesia. 1976;31(5):698–701.PubMedCrossRef
30.
go back to reference Polocki B, Czerwińska-Ciechan K, Berger H, Slizewska I, Szwaykowski W, Niewińska J. Ketamine used for anaesthesia in children for pneumoencephalography. Anaesth Resusc Intensive Ther. 1976;4(2):121–9.PubMed Polocki B, Czerwińska-Ciechan K, Berger H, Slizewska I, Szwaykowski W, Niewińska J. Ketamine used for anaesthesia in children for pneumoencephalography. Anaesth Resusc Intensive Ther. 1976;4(2):121–9.PubMed
31.
go back to reference Wilson E, Marx M, Montaldo AM, Arana-Iñiguez R. Effects of ketamine on the pressure of the cerebrospinal fluid. Variations of its effects. Acta Neurol Latinoam. 1976;22(1-4):10–6.PubMed Wilson E, Marx M, Montaldo AM, Arana-Iñiguez R. Effects of ketamine on the pressure of the cerebrospinal fluid. Variations of its effects. Acta Neurol Latinoam. 1976;22(1-4):10–6.PubMed
32.
go back to reference Crumrine RS, Nulsen FE, Weiss MH. Alterations in ventricular fluid pressure during ketamine anesthesia in hydrocephalic children. Anesthesiology. 1975;42(6):758–61.PubMedCrossRef Crumrine RS, Nulsen FE, Weiss MH. Alterations in ventricular fluid pressure during ketamine anesthesia in hydrocephalic children. Anesthesiology. 1975;42(6):758–61.PubMedCrossRef
34.
go back to reference Gardner AE, Dannemiller FJ, Dean D. Intracranial cerebrospinal fluid pressure in man during ketamine anesthesia. Anesth Analg. 1972;51:741–5.PubMed Gardner AE, Dannemiller FJ, Dean D. Intracranial cerebrospinal fluid pressure in man during ketamine anesthesia. Anesth Analg. 1972;51:741–5.PubMed
35.
go back to reference List WF, Crumrine RS, Cascorbi HF, Weiss MH. Increased cerebrospinal fluid pressure after ketamine. Anesthesiology. 1972;36:98–9.PubMedCrossRef List WF, Crumrine RS, Cascorbi HF, Weiss MH. Increased cerebrospinal fluid pressure after ketamine. Anesthesiology. 1972;36:98–9.PubMedCrossRef
36.
go back to reference Wyte SR, Shapiro HM, Turner P, Harris AB. Ketamine-induced intracranial hypertension. Anesthesiology. 1972;36:174–6.PubMedCrossRef Wyte SR, Shapiro HM, Turner P, Harris AB. Ketamine-induced intracranial hypertension. Anesthesiology. 1972;36:174–6.PubMedCrossRef
37.
go back to reference McDonald JW, Roeser NF, Silverstein FS, Johnston MV. Quantitative assessment of neuroprotection against NMDA-induced brain injury. Exp Neurol. 1989;106:289–96.PubMedCrossRef McDonald JW, Roeser NF, Silverstein FS, Johnston MV. Quantitative assessment of neuroprotection against NMDA-induced brain injury. Exp Neurol. 1989;106:289–96.PubMedCrossRef
38.
go back to reference Bhutta AT, Schmitz ML, Swearingen C, James LP, Wardbegnoche WL, Lindquist DM. Ketamine as a neuroprotective and anti-inflammatory agent in children undergoing surgery on cardiopulmonary bypass: a pilot randomized, double-blind, placebo-controlled trial. Pediatr Crit Care Med. 2012;13:328–37.PubMedCrossRef Bhutta AT, Schmitz ML, Swearingen C, James LP, Wardbegnoche WL, Lindquist DM. Ketamine as a neuroprotective and anti-inflammatory agent in children undergoing surgery on cardiopulmonary bypass: a pilot randomized, double-blind, placebo-controlled trial. Pediatr Crit Care Med. 2012;13:328–37.PubMedCrossRef
39.
go back to reference Takeshita H, Okuda Y, Sari A. The effects of ketamine on cerebral circulation and metabolism in man. Anesthesiology. 1972;36:69–75.PubMedCrossRef Takeshita H, Okuda Y, Sari A. The effects of ketamine on cerebral circulation and metabolism in man. Anesthesiology. 1972;36:69–75.PubMedCrossRef
40.
go back to reference Chi OZ, Wei HM, Klein SL, Weiss HR. Effect of ketamine on heterogeneity of cerebral microregional venous O2 saturation in the rat. Anesth Analg. 1994;79:860–6.PubMed Chi OZ, Wei HM, Klein SL, Weiss HR. Effect of ketamine on heterogeneity of cerebral microregional venous O2 saturation in the rat. Anesth Analg. 1994;79:860–6.PubMed
41.
go back to reference Miyamoto E, Nakao S, Tomimoto H, Wakita H, Yamada M, Masuzawa M, Takahira K, Sakamoto S, Shingu K. Ketamine attenuates hypocapnia-induced neuronal damage in the caudoputamen in a rat model of chronic cerebral hypoperfusion. Neurosci Lett. 2004;354:26–9.PubMedCrossRef Miyamoto E, Nakao S, Tomimoto H, Wakita H, Yamada M, Masuzawa M, Takahira K, Sakamoto S, Shingu K. Ketamine attenuates hypocapnia-induced neuronal damage in the caudoputamen in a rat model of chronic cerebral hypoperfusion. Neurosci Lett. 2004;354:26–9.PubMedCrossRef
42.
go back to reference Långsjö JW, Kaisti KK, Aalto S, Hinkka S, Aantaa R, Oikonen V, Sipilä H, Kurki T, Silvanto M, Scheinin H. Effects of subanesthetic doses of ketamine on regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology. 2003;99:614–23.PubMedCrossRef Långsjö JW, Kaisti KK, Aalto S, Hinkka S, Aantaa R, Oikonen V, Sipilä H, Kurki T, Silvanto M, Scheinin H. Effects of subanesthetic doses of ketamine on regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology. 2003;99:614–23.PubMedCrossRef
43.
go back to reference Pfenninger E, Reith A, Domino EF. Status of ketamine in anaesthesiology. Ann Arbor: NPP Books; 1990. p. 109–81. Pfenninger E, Reith A, Domino EF. Status of ketamine in anaesthesiology. Ann Arbor: NPP Books; 1990. p. 109–81.
44.
go back to reference Strebel S, Kaufmann M, Maître L, Schaefer HG. Effects of ketamine on cerebral blood flow velocity in humans: influence of pre-treatment with midazolam or esmolol. Anaesthesia. 1995;50:223–8.PubMedCrossRef Strebel S, Kaufmann M, Maître L, Schaefer HG. Effects of ketamine on cerebral blood flow velocity in humans: influence of pre-treatment with midazolam or esmolol. Anaesthesia. 1995;50:223–8.PubMedCrossRef
45.
go back to reference Nimkoff L, Quinn C, Silver P, Sagy M. The effects of intravenous anesthetics on intracranial pressure and cerebral perfusion pressure in two feline models of brain edema. J Crit Care. 1997;12:132–6.PubMedCrossRef Nimkoff L, Quinn C, Silver P, Sagy M. The effects of intravenous anesthetics on intracranial pressure and cerebral perfusion pressure in two feline models of brain edema. J Crit Care. 1997;12:132–6.PubMedCrossRef
46.
go back to reference Ohata H, Iida H, Nagase K, Dohi S. The effects of topical and intravenous ketamine on cerebral arterioles in dogs receiving pentobarbital or isoflurane anesthesia. Anesth Analg. 2001;93:697–702.PubMedCrossRef Ohata H, Iida H, Nagase K, Dohi S. The effects of topical and intravenous ketamine on cerebral arterioles in dogs receiving pentobarbital or isoflurane anesthesia. Anesth Analg. 2001;93:697–702.PubMedCrossRef
47.
go back to reference Nagase K, Ida H, Dohi S. Effects of ketamine on isoflurane- and sevoflurane-induced cerebral vasodilation in rabbits. J Neurosurg Anesthesiol. 2003;15:98–103.PubMedCrossRef Nagase K, Ida H, Dohi S. Effects of ketamine on isoflurane- and sevoflurane-induced cerebral vasodilation in rabbits. J Neurosurg Anesthesiol. 2003;15:98–103.PubMedCrossRef
Metadata
Title
Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized controlled trials
Authors
Xin Wang
Xibing Ding
Yao Tong
Jiaying Zong
Xiang Zhao
Hao Ren
Quan Li
Publication date
01-12-2014
Publisher
Springer Japan
Published in
Journal of Anesthesia / Issue 6/2014
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI
https://doi.org/10.1007/s00540-014-1845-3

Other articles of this Issue 6/2014

Journal of Anesthesia 6/2014 Go to the issue