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Mannitol for acute traumatic brain injury

  1. Abel Wakai1,*,
  2. Ian G Roberts2,
  3. Gillian Schierhout3

Editorial Group: Cochrane Injuries Group

Published Online: 8 OCT 2008

Assessed as up-to-date: 28 FEB 2006

DOI: 10.1002/14651858.CD001049.pub4

Database Title

Additional Information

How to Cite

Wakai A, Roberts IG, Schierhout G. Mannitol for acute traumatic brain injury. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD001049. DOI: 10.1002/14651858.CD001049.pub4.

Author Information

  1. 1

    Sunnybrook Health Sciences Centre, Division of Emergency Medicine, Toronto, Ontario, Canada

  2. 2

    London School of Hygiene & Tropical Medicine, Cochrane Injuries Group, London, UK

  3. 3

    London School of Hygiene & Tropical Medicine, c/o Cochrane Injuries Group, London, UK

*Abel Wakai, Division of Emergency Medicine, Sunnybrook Health Sciences Centre, Suite C7-16, Toronto, Ontario, M4N 3M5, Canada. abelwakai@gmail.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 8 OCT 2008

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ARTICLE TOOLS

Summary (57K)Standard (151K)Full (173K)
 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Mannitol is widely used in the control of raised intracranial pressure following brain injury. A 1995 survey of the critical care management of head-injured patients in the United States showed that 83% of centres used osmotic diuretics in more than half of severely head-injured patients (Ghajar 1995). A survey in the United Kingdom showed that 100% of neurosurgical centres used mannitol in the treatment of raised intracranial pressure (Jeevaratnam 1996; Matta 1996). The effectiveness of mannitol for head-injured patients in a critical condition is considered to be well established, without the need for randomised controlled trials.

For other patients, the Brain Trauma Foundation Guidelines Task Force of the American Association of Neurological Surgeons and Joint Section in Neurotrauma and Critical Care (Task Force 1995) recommend that mannitol be used only if the patient has signs of raised intracranial pressure (ICP) or deteriorating neurological status. In these circumstances, any adverse effects are most likely to be outweighed by therapeutic benefit. Nevertheless, the guidelines acknowledge that this is an area of considerable clinical uncertainty. There is uncertainty over the optimal treatment regimen, over the effectiveness of mannitol as compared to other ICP-lowering agents and over the usefulness of mannitol given at other stages following head injury, for example in the pre-hospital setting, prior to volume resuscitation.

We conducted a systematic review of randomised controlled trials that compared different mannitol treatment regimens, or compared mannitol to alternative interventions or placebo, at any stage in the acute management of head injury.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

1. To compare the effectiveness of mannitol therapy when given in different doses and for different durations.
2. To quantify the effectiveness of mannitol compared to other ICP-lowering agents.
3. To quantify the effectiveness of mannitol administration given at other stages following head injury.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Controlled trials in which subjects were assigned to treatment or control groups (placebo-controlled, no drug, different drug or different mannitol regimen) on the basis of random or quasi-random allocation. We excluded trials with a cross-over design.

 

Types of participants

Participants had a clinically defined acute traumatic brain injury of any severity.

 

Types of interventions

The treatment group received mannitol in any dose for any duration, at any time within eight weeks following injury. The control group received any of the following: mannitol in a different dose from the treatment group, another ICP-lowering agent such as barbiturates or placebo or standard care only.

 

Types of outcome measures

We aimed to extract from each trial the number of patients originally allocated to each group. Within each group, we aimed to extract the number of participants who died from any cause during the follow-up period or who were dead, in a vegetative state or severely disabled, compared to moderate or good recovery (according to Glasgow Coma Scale [GCS] criteria).

 

Search methods for identification of studies

An updated search was carried out using the following electronic databases and strategies in March 2006. A search was also carried out of web-based trials databases and general search engines.

 

Electronic searches

The review drew on the search strategy for the group as a whole, which is described in Appendix 1. The following databases were searched:

  • Cochrane Injuries Group Specialised Register
  • Cochrane Central Register of Controlled Trials (2006 issue 1 (CD))
  • EMBASE (to March 2006 (OVID))
  • Science Citation Index (to March 2006)

 

Searching other resources

The reference lists of all relevant articles identified were checked. A letter was sent to the first author of reports to ask for further information on the published report and asking them to assist in identifying any further trials which may have been conducted by them, or other investigators. Eligibility was determined by reading the reports of possible trials.

 

Data collection and analysis

We determined eligibility by reading the reports of possible trials and corresponding with the trialists. The reviewers independently rated quality of allocation concealment and independently extracted the data. We resolved disagreement by discussion. We calculated relative risks and 95% confidence intervals for each trial on an intention to treat basis. For trials which used comparable treatment regimens, we planned to calculate summary relative risks and 95% confidence intervals using a fixed effects model, and to stratify the analyses on allocation concealment.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

Four studies met the inclusion criteria.

Sayre 1996 compared the pre-hospital administration of mannitol with placebo (normal saline). Eligible patients were those with moderate and severe head injury (GCS 11 or less), above 18 years of age. Patients were excluded if they may have been pregnant, had already received a diuretic, or were receiving cardiopulmonary resuscitation. The mannitol group received 5ml/kg of 20% mannitol through a large bore IV catheter over five minutes. The placebo group was given 5ml/kg of 0.9% saline solution. Forty-four participants were randomised; three were later excluded as they were found to be ineligible. The treatment to which these three patients were allocated, as well as follow-up information were unavailable. Therefore, the analysis was based upon 20 participants in the mannitol group and 21 participants in the placebo group. Length of follow-up was for two hours after arrival at the hospital.

Schwartz 1984 compared mannitol to pentobarbital. Patients with severe head injury (GCS <8), and with raised ICP for longer than 15 minutes were eligible. Treatment allocation was stratified according to the presence of intracranial haematomas. The mannitol group received 20% mannitol solution at an initial dose of 1g per kg. Additional increments were given to maintain the intracranial pressure at less than 20 torr, within a serum osmolality of mannitol of 320mOs/litre. The pentobarbital group received pentobarbital as an intravenous (IV) bolus of up to 10mg/kg, followed by a continuous infusion at 0.5 to 3mg/kg/hr, provided that CPP remained above 50 torr. Additional increments of pentobarbital were given to maintain the intracranial pressure at less than 20 torr. For subsequent episodes of raised ICP, there was some cross-over to the alternate treatment group, but the analysis was on the original intent-to-treat. Seventy participants were randomised; 11 were later deemed ineligible and excluded. Data on the treatment to which these 11 patients were allocated and follow-up information were unavailable. Therefore, the analysis was based on 31 participants in the mannitol group and 28 participants in the pentobarbital group. Length of follow-up was one year.

Smith 1986 compared two regimens for guiding the administration of mannitol, one according to neurological signs and physiological measurements, and the other using ICP monitoring. Participants had a severe head injury (GCS 8 or less). The protocol for the first group used neurological signs, GCS, ventilatory values and arterial blood gas to guide administration of mannitol. In the second group, a 250ml bolus of mannitol (20%) was given if ICP > 25mmHg, and subsequent boluses were given incrementally. Eighty participants were randomised. Data were available for 40 participants in the first group, and 37 participants in the ICP-directed treatment group. Follow-up was one year.

Vialet 2003 compared mannitol to hypertonic saline. Eligible patients were those with severe head injury (GCS <8) who required intravenous infusions of an osmotic agent to treat episodes of intracranial hypertension resistant to standard therapy (cerebrospinal fluid drainage, volume expansion and/or inotropic support, hyperventilation). The mannitol group received 20% mannitol solution. The hypertonic saline group received 7.5% hypertonic saline. The infused volume was the same for both solutions: 2 ml/kg body weight in 20 minutes. The aim was to decrease ICP to <25 mm Hg or to increase CPP to >70 mm Hg. In case the first infusion failed, the patient received a second infusion within ten minutes after the end of the first infusion. Treatment failure was defined as the inability to decrease ICP to <35 mm Hg or to increase CPP to >70 mm Hg with two consecutive infusions of the selected osmotic solution. In that case, the protocol was stopped, and patients were followed up for mortality or 90-day neurologic status. Because 20% mannitol can crystallize at ambient temperature, injections could not be performed in a blinded manner. Twenty patients were randomised, ten to each group. Outcome was assessed at 90 days using the Glasgow Outcome Scale administered by a practitioner who was blind to acute patient care.

 

Risk of bias in included studies

Sayre 1996: The study was randomised and double-blind. Allocation concealment was by pharmacy-prepared blinded solutions.

Schwartz 1984: The study was randomised and single-blind. Allocation concealment was by using serially numbered sealed envelopes.

Smith 1986:The study was randomised but not reported as double-blind. Allocation concealment was by the use of sealed envelopes.

Vialet 2003: The study was randomised but allocation concealment was not described. Outcome assessment was blind to acute clinical care.

 

Effects of interventions

One trial compared ICP-directed therapy to 'standard care' in which mannitol therapy was directed by neurological signs (Smith 1986). The study was randomised and allocation concealment was by the use of sealed envelopes. For ICP-directed treatment compared to treatment based on neurological signs, the RR for death was 0.83 (95% CI 0.47 to 1.46); this trial demonstrated a similar effect for death or severe disability (RR = 0.88; 95% CI 0.55 to 1.38).

One trial compared mannitol to pentobarbital (Schwartz 1984). This trial was randomised and single blind. Only patients with known raised ICP were included. For mannitol compared to pentobarbital in the treatment of patients with raised ICP, the RR for death was 0.85 (95% CI 0.52 to 1.38).

One trial compared mannitol to hypertonic saline (Vialet 2003). This trial was randomised and single blind. Only patients with head injury and persistent coma who required osmotherapy to treat episodes of intracranial hypertension resistant to standard therapy were included. For mannitol compared to hypertonic saline in the treatment of refractory intracranial hypertension episodes in comatose patients with severe head injury, the RR for death was 1.25 (95% CI 0.47 to 3.33).

The effectiveness of pre-hospital administration of mannitol against placebo was investigated in Sayre 1996. This study was randomised and allocation concealment was through pharmacy prepared blinded solutions. For pre-hospital infusion of mannitol compared to placebo in patients with head injury and multiple trauma, the RR for death was 1.75 (95% CI 0.48 to 6.38).

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

There were few eligible trials of mannitol therapy in head-injured patients.

ICP-directed treatment showed a small beneficial effect on mortality when compared to treatment directed according to neurological signs and physiological indicators (RR = 0.83; 95% CI 0.47 to 1.46). The method of allocation concealment in this study was adequate to prevent foreknowledge of treatment, and was unlikely to have led to bias. Owing to small patient numbers, the effect measure is imprecise. It must be noted that in this study the ICP-directed protocol initiated mannitol only when the ICP rose to above 25mmHg. Therefore these results cannot be extrapolated to ICP-directed protocols which initiate mannitol therapy at a lower level.

Mannitol therapy may have a beneficial effect on mortality when compared to pentobarbital therapy. However, the single trial which tested this (Schwartz 1984) yielded an imprecise effect measure, which also may be compatible with no difference, or a beneficial effect of pentobarbital. The trial was testing an initial treatment of mannitol compared to pentobarbital as some patients later received the alternate therapy if the allocated therapy failed to control ICP.

Mannitol therapy may have a detrimental effect on mortality when compared to hypertonic saline therapy. The single trial which compared mannitol to hypertonic saline (Vialet 2003) was too small for reliable conclusions. The trial was not designed to test the effect of these osmotic agents on neurologic recovery or death.

The single trial which compared pre-hospital administration of mannitol to placebo showed an increase in mortality amongst the mannitol-treated patients (RR = 1.75; 95% CI 0.48 to 6.38). The estimate yielded by this trial is imprecise owing to the small sample size. The effect measure also may be compatible with no difference, or a beneficial effect of pre-hospital administration of mannitol.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

 

Implications for practice

There is insufficient reliable evidence to make recommendations on the use of mannitol in the management of patients with traumatic brain injury.

 
Implications for research

There are many unanswered questions regarding the optimal use of mannitol following acute traumatic head injury. The widespread current use of mannitol, and lack of clarity regarding optimal administration, present an ideal opportunity for the conduct of randomised controlled trials.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
Download statistical data

 
Comparison 1. ICP-directed mannitol ('treatment') compared to mannitol according to neurological signs ('control')
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Death177Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.47, 1.46]
 2 Death or severe disability177Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.55, 1.38]

 
Comparison 2. Mannitol versus pentobarbital
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Death159Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.52, 1.38]

 
Comparison 3. Mannitol versus hypertonic saline
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Death120Risk Ratio (M-H, Fixed, 95% CI)1.25 [0.47, 3.33]

 
Comparison 4. Mannitol versus placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Death141Risk Ratio (M-H, Fixed, 95% CI)1.75 [0.48, 6.38]

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Appendix 1. Search strategy

Cochrane Injuries Group Specialised Register
((brain or head) and (injur* or trauma*)) and (respirat* or hyperventilat*)

Cochrane Central Register of Controlled Trials 2006 issue 1 (CD)
PubMed to 04/2005 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi)
#1 explode "Mannitol" / all SUBHEADINGS
#2 explode "Diuretics-Osmotic" / all SUBHEADINGS
#3 mannitol* or osmotic diuretic*
#4 explode "Craniocerebral-Trauma" / all SUBHEADINGS
#5 (explode "Intracranial-Pressure" / all SUBHEADINGS) or (explode "Intracranial-Hypotension" / all SUBHEADINGS) or (explode "Intracranial-Hypertension" / all SUBHEADINGS)
#6 explode "Brain-Injuries" / all SUBHEADINGS
#7 (head or brain) and (injur* or trauma*)
#8 intracranial pressure
#9 #1 or #2 or #3
#10 #4 or #5 or #6 or #7 or #8
#11 #9 and #10
#12 RCT filter (Clarke 2001)
#13 #11 and #12

EMBASE to March 2006 (OVID)
#1 exp Mannitol/
#2 exp Osmotic Diuretic Agent/
#3 mannitol$ or osmotic diuretic$
#4 exp Head Injury/
#5 (exp Intracranial-Pressure/) or (exp Intracranial-Hypotension/) or (exp Intracranial-Hypertension/)
#6 exp Brain-Injury/
#7 (head or brain) and (injur$ or trauma$)
#8 (intracranial pressure).ti,ab
#9 #1 or #2 or #3
#10 #4 or #5 or #6 or #7 or #8
#11 #9 and #10
#12 exp Randomized Controlled Trial/
#13 randomi$ or (single adj blind$) or (double adj blind$) or (controlled adj trial$)
#14 #12 or #13
#15 #14 and #11

Science Citation Index to March 2006
(mannitol OR diuretic*) AND (intracranial pressure OR intracranial hypotension OR intracranial hypertension) AND trial*

 

Feedback

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Mannitol for acute traumatic brain injury

 

Summary

A. The search strategy would be clearer if the reviewer specified what additional search terms were used within the Injuries Group database to identify relevant articles (e.g., mannitol And acute brain injury). Also, the report does not specify whether any other databases, such as Medline or Embase, were searched, and if so, what search terms were used. The search should specify the total number of reports that were identified by the search strategy.

B. Would it be correct to interpret the review as demonstrating that there is no good evidence (i.e. no RCT's comparing mannitol to placebo or alternate therapies) to support our current mannitol use post-head injury? Presumably current use of mannitol by clinicians is based primarily on the pharmacological activities of mannitol, observational human studies, and animal evidence supporting its potential benefit.

 

Reply

A. We did not use any additional search terms in the Injuries Group database apart from 'mannitol'. No other databases, such as EMBASE, were searched separately (these searches were already included in the Injuries Group database).

B. Yes - the review concludes that there is a lack of evidence for effectiveness, which is not the same as saying there is evidence of a lack of effectiveness.

 

Contributors

Dr Michael Bullard

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Last assessed as up-to-date: 28 February 2006.

DateEventDescription
10 July 2008AmendedConverted to new review format.


 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Protocol first published: Issue 1, 1998
Review first published: Issue 1, 1998

DateEventDescription
22 November 2006AmendedNovember 2006
In response to concerns raised about the integrity of the data from the trials by Cruz et al, the Cochrane Injuries Group undertook an investigation in which attempts were made to find out where the patients were recruited and to access the original trial data for external validation. Despite considerable efforts the Group is unable to provide any reassurance about the integrity of trial data and for this reason the trials in question have been removed from the review.


 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

AW ran the searches, screened the citations for eligibility extracted data, entered data into RevMan and wrote the updated review.

IR screened citations, extracted data, helped to write the original review.

GS designed and ran the searches, screened the citations for eligibility, contacted authors, extracted data, entered data into RevMan and wrote up the original review.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Data and analyses
  9. Appendices
  10. Feedback
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Internal sources

  • Department of Emergency Medicine, St. Vincent's University Hospital, Dublin 4, Ireland.

 

External sources

  • NHS R& D Programme: mother and child health, UK.
  • The Higher Specialist Training Scheme in Emergency Medicine, Ireland.

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
Sayre 1996 {published data only}
  • Sayre MR, Daily SW, Stern SA, Storer DL, van Loveren HR, Hurst JD. Out-of-hospital administration of mannitol does not change systolic blood pressure. Academic Emergency Medicine 1996;3(9):840-8. [MEDLINE: 1997024527]
    Direct Link:
Schwartz 1984 {published data only}
  • Schwartz ML, Tator CH, Rowed DW, Reid SR, Meguro K, Andrews DF. The University of Toronto head injury treatment study: a prospective, randomized comparison of pentobarbital and mannitol. Canadian Journal of Neurological Sciences 1984;11(4):434-40. [MEDLINE: 1985098889]
Smith 1986 {published data only}
Vialet 2003 {published data only}
  • Vialet R, Albanese J, Thomachot L, Antonini F, Bourgouin A, Alliez B, et al. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Critical Care Medicine 2003;31(6):1683-7. [MEDLINE: 12794404]

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
Battison 2005 {published data only}
  • Battison C, Andrews PJ, Graham C, Petty T. Randomized, controlled trial of the effect of a 20% mannitol solution and a 7.5% saline/6% dextran solution on increased intracranial pressure after brain injury. Critical Care Medicine 2005;33(1):196-202. [MEDLINE: 15644669]
Cruz 2001 {published data only}
  • Cruz C, Minoja G, Okuchi K. Improving clinical outcomes from acute subdural hematomas with emergency preoperative administration of high doses of mannitol: a randomized trial. Neurosurgery 2001;49(4):864-71.
Cruz 2002 {published data only}
  • Cruz C, Minoja G, Okuchi K. Major clinical and physiological benefits of early high doses of mannitol for intraparenchymal temporal lobe hemorrhages with abnormal pupilary widening. Neurosurgery 2002;51(3):628-38.
Cruz 2004 {published data only}
  • Cruz J, Minoja G, Okuchi K, Facco E. Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scores of 3 and bilateral abnormal pupillary widening: a randomized trial. Journal of Neurosurgery 2004;100(3):376-83. [MEDLINE: 15035271]
Fortune 1995 {published data only}
  • Fortune JB, Feustel PJ, Graca I, Hasselbarth J, Kuehler DH. Effect of hyperventilation, mannitol, and ventriculostomy drainage on cerebral blood-flow after head-injury. Journal of Trauma-Injury Infection and Critical Care 1995;39(6):1091-9.
Gaab 1989 {published data only}
  • Gaab MR, Seegers K, Goetz C. THAM (Tromethamine, "Tris-Buffer"): Effective therapy of traumatic brain swelling?. In: Hoff JT, Betz AL editor(s). Intracranial Pressure VII. Berlin Heidelberg: Springer-Verlag, 1989:616-9.
Levin 1979 {published data only}
Midgely 1993 {published data only}
  • Midgley S. CPP and SJO2 with ICP Reduction Therapy After Severe Head Injury. Intracranial Pressure. New York: Springer-Verlag, 1993:558-63.
Smedema 1993 {published data only}
  • Smedema RJA. Comparison Study Between Mannitol and Glycerol Therapy in Reducing Intracranial Pressure. Intracranial Pressure. Vol. 8, New York: Springer-Verlag, 1993:605-8.

Additional references

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
Ghajar 1995
Jeevaratnam 1996
  • Jeevaratnam DR, Menon DK. Survey of intensive care of severely head injured patients in the United Kingdom. BMJ 1996;312:994-7.
Matta 1996
  • Matta B, Menon D. Severe head injury in the United Kingdom and Ireland: a survey of practice and implications for management. Critical Care Medicine 1996; 24;10:1743-8.
Task Force 1995
  • Task force of the American Association of Neurological Surgeons and Joint Section in Neurotrauma and Critical Care. Guidelines for the management of severe head injury. Brain Trauma Foundation, 1995.
Summary (57K)Standard (151K)Full (173K)