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Resúmenes Epistemonikos
Medwave 2018;18(7):e7321 doi: 10.5867/medwave.2018.07.7321
Tomografía computarizada sin contraste para el diagnóstico de hemorragia subaracnoidea no traumática
Non-contrast computed tomography for the diagnosis of non-traumatic subarachnoid hemorrhage
Yerko Suazo, Gabriel Rada
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Palabras clave: Non-contrast computed tomography, subarachnoid hemorrhage, Epistemonikos, GRADE.

Abstract

INTRODUCTION
Subarachnoid hemorrhage is a neurosurgical emergency that requires timely diagnosis due to its severity and the existence of therapeutic measures that are effective when carried out in time. The most used diagnostic sequence to rule it out is computed tomography without contrast which, if negative, is followed by lumbar puncture. However, it has been suggested that a negative non-contrast computed tomography (without blood) may rule out the diagnosis.

METHODS
To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.

RESULTS AND CONCLUSIONS
We identified three systematic reviews including nine studies. We concluded the diagnostic accuracy of non-contrast computed tomography is probably very high, but the clinical impact of relying only on this test has not yet been evaluated.


 
Problem

It is estimated that subarachnoid hemorrhage could be responsible for 1% of headaches in emergency services [1],[2]. Its early diagnosis is very important since it is a neurosurgical emergency with very high morbidity and mortality, and there are therapies that can make an important difference if timely implemented [2]. Although it has a characteristic clinical presentation, the symptoms and signs are not enough to rule it out [1],[2]. The most commonly used sequence is non-contrast computed tomography followed by a lumbar puncture, ruling out the condition with both results negative. However, lumbar puncture is not risk-free (infection, hematoma, and stress for the patient) and its added value is a matter of debate [1],[2]

Methods

To answer the question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others, to identify systematic reviews and their included primary studies. We extracted data from the identified reviews and reanalyzed data from primary studies included in those reviews. With this information, we generated a structured summary denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos) using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies when it is possible, a summary of findings table following the GRADE approach and a section of other considerations for decision-making. 

Key messages

  • Diagnostic accuracy of non-contrast computed tomography for non-traumatic subarachnoid hemorrhage is probably very high, although its clinical impact has not yet been evaluated.
About the body of evidence for this question

What is the evidence.
See evidence matrix in Epistemonikos later

We found three systematic reviews [1],[2],[3] that included nine primary studies overall [4],[5],[6],[7],[8],[9],[10],[11],[12], none of them a randomized trial. We did not find studies evaluating the clinical impact.

We excluded one systematic review [3] because it mixed non-traumatic with peri-mesencephalic subarachnoid hemorrhage, which is considered a different clinical entity. 

What types of patients were included*

All studies included patients older than 11 years, four studies included adults without specifying age [5],[6],[9],[12] and four studies only included patients without neurological deficit [5],[7],[11],[12].

Five studies evaluated patients with less than 6 hours symptom onset [6],[7],[9],[11],[12], one study with less than 12 hours [5] and three studies did not specify it [4],[8],[10].

One study[6] only included patients with negative non-contrast computed tomography for subarachnoid hemorrhage.

What types of interventions were included*

Five studies used 16-slice or higher computed tomography [6],[7],[9],[11],[12] and the others did not described the type of computed tomography used[4],[5],[8],[10]

As gold standard, six studies used lumbar puncture, imaging, and follow-up[6],[7],[8],[9],[11],[12] and the rest did not reported it [4],[5],[10].

Five studies followed all of their patients [6],[7][8],[9],[11], three studies did not follow up patients [4],[5],[10] and one study had an incomplete follow up (86% of patients)[12].

What types of outcomes
were measured

The different systematic reviews pooled outcomes as follows: specificity, sensitivity, positive likelihood ratio (LR +), negative likelihood ratio (LR -), true positives, false negatives, false positives and true negatives.

* The information about primary studies is extracted from the systematic reviews identified, unless otherwise specified.

Summary of findings

Information on the diagnostic accuracy of non-contrast computed tomography for non-traumatic subarachnoid hemorrhage is based on 9 primary studies [5],[6],[7],[8],[9],[10],[11],[12],[13]. All of these measured specificity, sensitivity, LR + and LR- of the non-contrast computed tomography for non-traumatic subarachnoid hemorrhage.

The summary of the findings is as follows:

  • It is not clear if non-contrast computed tomography for non-traumatic subarachnoid hemorrhage impacts mortality and morbidity because we did not find studies evaluating this aspect
  • Diagnostic accuracy of non-contrast computed tomography for non-traumatic subarachnoid hemorrhage is probably very high.

Follow the link to access the interactive version of this table (Interactive Summary of Findings – iSoF)

Other considerations for decision-making

To whom this evidence does and does not apply

  • The evidence analyzed in this summary applies to adults without neurological deficit, with early onset of symptoms (less than 6 hours), that consult to emergency services for intense headache, evaluated by a radiologist, with a modern computed tomography.
  • This evidence should be applied cautiously to children, adolescents and especially to patients with neurological deficit, since these groups are not well represented in the studies.
About the outcomes included in this summary
  • We conducted searches on the diagnostic impact of non-contrast computed tomography, but no systematic reviews that answered this question were found. So, the search was expanded in order to find systematic reviews on diagnostic accuracy, which reported sensitivity, specificity and likelihood ratios.
Balance between benefits and risks, and certainty of the evidence
  • Because of the lack of systematic reviews addressing diagnostic impact, It is difficult to make a balance between risk and benefits. However, based on the good diagnostic accuracy, it is reasonable to anticipate a balance in favour of non contrast computed tomography. On the other hand, adverse effects are only those derived from radiation and from the decisions associated to false positives and false negatives (false security or unnecessary actions).
Resource considerations
  • Reducing the need to perform contrasted exams or lumbar puncture could lead to savings, particularly in scenarios where carrying out this procedure requires unavailable resources or transfer to other centers.
What would patients and their doctors think about this intervention
  • With the information presented in this summary, most clinicians should lean in favor of simply relying on non contrast computed tomography.
  • However, due to the lack of evidence on diagnostic impact in clinical practice, the decision making in this area will probably vary.

Differences between this summary and other sources

  • The systematic reviews identified agree with this summary in terms of the accuracy of computed tomography in this setting, and the lack of benefit of performing a subsequent lumbar puncture. On the other hand they conclude computed tomography and lumbar puncture, or even angiography, may be necessary in patients with symptoms for more than 6 hours.
  • The guideline of the American Heart Association /American Stroke Association recommends performing lumbar puncture whenever there is suspicion of subarachnoid hemorrhage with negative computed tomography [14]. The European guideline recommends performing lumbar puncture after early negative computed tomography only if there is high clinical suspicion of subarachnoid hemorrhage [15].
Could this evidence change in the future?
  • The probability that future research changes the conclusions of this summary for diagnostic impact is high, due to the uncertainty of the existing evidence, and low for diagnostic accuracy.
  • The American Heart Association presents one study in its clinical guideline that is not included in any systematic review [16], where patients are separated in terms of days of evolution, not in hours. New reviews incoporating this variable might be of value.
  • We identified one ongoing systematic review of cost-benefit in PROSPERO [17], and one observational study in the Clinical Trials Registry Platform of the World Health Organization [18].
How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Accuracy of computed tomography without contrast for the diagnosis of non-traumatic subarachnoid hemorrhage

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier.

After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

This article is part of the Epistemonikos Evidence Synthesis project. It is elaborated with a pre-established methodology, following rigorous methodological standards and internal peer review process. Each of these articles corresponds to a summary, denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos), whose main objective is to synthesize the body of evidence for a specific question, with a friendly format to clinical professionals. Its main resources are based on the evidence matrix of Epistemonikos and analysis of results using GRADE methodology. Further details of the methods for developing this FRISBEE are described here (http://dx.doi.org/10.5867/medwave.2014.06.5997)

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

Potential conflicts of interest

The authors do not have relevant interests to declare.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

INTRODUCTION
Subarachnoid hemorrhage is a neurosurgical emergency that requires timely diagnosis due to its severity and the existence of therapeutic measures that are effective when carried out in time. The most used diagnostic sequence to rule it out is computed tomography without contrast which, if negative, is followed by lumbar puncture. However, it has been suggested that a negative non-contrast computed tomography (without blood) may rule out the diagnosis.

METHODS
To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.

RESULTS AND CONCLUSIONS
We identified three systematic reviews including nine studies. We concluded the diagnostic accuracy of non-contrast computed tomography is probably very high, but the clinical impact of relying only on this test has not yet been evaluated.

Autores: Yerko Suazo[1,2], Gabriel Rada[2,3,4,5,6]

Filiación:
[1] Facultad de Medicina, Universidad de Chile, Santiago, Chile
[2] Proyecto Epistemonikos, Santiago, Chile
[3] Centro Evidencia UC, Pontificia Universidad Católica de Chile
[4] Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[5] The Cochrane Collaboration
[6] GRADE working group

E-mail: radagabriel@epistemonikos.org

Correspondencia a:
[1] Centro Evidencia UC
Pontificia Universidad Católica de Chile
Diagonal Paraguay 476
Santiago
Chile

Citación: Suazo Y, Rada G. Non-contrast computed tomography for the diagnosis of non-traumatic subarachnoid hemorrhage. Medwave 2018;18(7):e7321 doi: 10.5867/medwave.2018.07.7321

Fecha de envío: 3/6/2018

Fecha de aceptación: 10/9/2018

Fecha de publicación: 7/11/2018

Origen: Este artículo es producto del Epistemonikos Evidence Synthesis Project de la Fundación Epistemonikos, en colaboración con Medwave para su publicación.

Tipo de revisión: Con revisión por pares sin ciego por parte del equipo metodológico del Epistemonikos Evidence Synthesis Project.

Ficha PubMed

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  1. Dubosh NM, Bellolio MF, Rabinstein AA, Edlow JA. Sensitivity of Early Brain Computed Tomography to Exclude Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis. Stroke; a journal of cerebral circulation. 2016;47(3):750-5.
  2. Carpenter CR, Hussain AM, Ward MJ, Zipfel GJ, Fowler S, Pines JM, Sivilotti ML. Spontaneous Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis Describing the Diagnostic Accuracy of History, Physical Exam, Imaging, and Lumbar Puncture with an Exploration of Test Thresholds. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2016;23(9):963-1003.
  3. García-Perdomo HA, Peña E, Abello AL. Conventional brain computed tomography for the diagnosis of nontraumatic subarachnoid hemorrhage: A systematic review. Revista Gastrohnup. 2015;17(1):25-32.
  4. O'Neill J, McLaggan S, Gibson R. Acute headache and subarachnoid haemorrhage: a retrospective review of CT and lumbar puncture findings. Scottish medical journal. 2005;50(4):151-3.
  5. van der Wee N, Rinkel GJ, Hasan D, van Gijn J. Detection of subarachnoid haemorrhage on early CT: is lumbar puncture still needed after a negative scan?. Journal of neurology, neurosurgery, and psychiatry. 1995;58(3):357-9.
  6. Mark DG, Hung YY, Offerman SR, Rauchwerger AS, Reed ME, Chettipally U, Vinson DR, Ballard DW, Kaiser Permanente CREST Network Investigators. Nontraumatic subarachnoid hemorrhage in the setting of negative cranial computed tomography results: external validation of a clinical and imaging prediction rule. Annals of emergency medicine. 2013;62(1):1-10.e1.
  7. Backes D, Rinkel GJ, Kemperman H, Linn FH, Vergouwen MD. Time-dependent test characteristics of head computed tomography in patients suspected of nontraumatic subarachnoid hemorrhage. Stroke. 2012;43(8):2115-9.
  8. Boesiger BM, Shiber JR. Subarachnoid hemorrhage diagnosis by computed tomography and lumbar puncture: are fifth generation CT scanners better at identifying subarachnoid hemorrhage?. The Journal of emergency medicine. 2005;29(1):23-7.
  9. Stewart H, Reuben A, McDonald J. LP or not LP, that is the question: gold standard or unnecessary procedure in subarachnoid haemorrhage?. Emergency medicine journal : EMJ. 2014;31(9):720-3.
  10. Carstairs SD, Tanen DA, Duncan TD, Nordling OB, Wanebo JE, Paluska TR, Theodore N, Riffenburgh RH. Computed tomographic angiography for the evaluation of aneurysmal subarachnoid hemorrhage. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2006;13(5):486-92.
  11. Blok KM, Rinkel GJ, Majoie CB, Hendrikse J, Braaksma M, Tijssen CC, Wong YY, Hofmeijer J, Extercatte J, Kerklaan B, Schreuder TH, ten Holter S, Verheul F, Harlaar L, Pruissen DM, Kwa VI, Brouwers PJ, Remmers MJ, Schonewille WJ, Kruyt ND, Vergouwen MD. CT within 6 hours of headache onset to rule out subarachnoid hemorrhage in nonacademic hospitals. Neurology. 2015;84(19):1927-32.
  12. Perry JJ, Stiell IG, Sivilotti ML, Bullard MJ, Emond M, Symington C, Sutherland J, Worster A, Hohl C, Lee JS, Eisenhauer MA, Mortensen M, Mackey D, Pauls M, Lesiuk H, Wells GA. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. BMJ (Clinical research ed.). 2011;343:d4277.
  13. Ward, M. J., Bonomo, J. B., Adeoye, O., Raja, A. S. and Pines, J. M. (2012), Cost-effectiveness of Diagnostic Strategies for Evaluation of Suspected Subarachnoid Hemorrhage in the Emergency Department. Academic Emergency Medicine, 19: 1134–1144.
  14. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P ; on behalf of the American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2012;43:1711–1737. | CrossRef |
  15. Steiner T, Juvela S, Unterberg A, Jung C, Forsting M, Rinkel G, European Stroke Organization Guidelines for the Management of Intracranial Aneurysms and Subarachnoid Haemorrhage. Cerebrovasc Dis 2013;35:93-112.
  16. Sidman R, Connolly E, Lemke T. Subarachnoid hemorrhage diagnosis: lumbar puncture is still needed when the computed tomography scan is normal. Acad Emerg Med. 1996; 3:827–31.
  17. Midhun Mohan, Ola Rominiyi, Aswin Chari Chari. Subarachnoid haemorrhage with negative initial neurovascular imaging: a systematic review and meta-analysis of delayed diagnoses and clinical outcomes. PROSPERO 2016 CRD42016035376. | CrossRef | Link |
  18. Dailler F et al. Observational Study of Patients With Subarachnoid Hemorrhage (ProReSHA). WHO, Clinical Trials Registry Platform. NCT02890004. | Link |
Dubosh NM, Bellolio MF, Rabinstein AA, Edlow JA. Sensitivity of Early Brain Computed Tomography to Exclude Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis. Stroke; a journal of cerebral circulation. 2016;47(3):750-5.

Carpenter CR, Hussain AM, Ward MJ, Zipfel GJ, Fowler S, Pines JM, Sivilotti ML. Spontaneous Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis Describing the Diagnostic Accuracy of History, Physical Exam, Imaging, and Lumbar Puncture with an Exploration of Test Thresholds. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2016;23(9):963-1003.

García-Perdomo HA, Peña E, Abello AL. Conventional brain computed tomography for the diagnosis of nontraumatic subarachnoid hemorrhage: A systematic review. Revista Gastrohnup. 2015;17(1):25-32.

O'Neill J, McLaggan S, Gibson R. Acute headache and subarachnoid haemorrhage: a retrospective review of CT and lumbar puncture findings. Scottish medical journal. 2005;50(4):151-3.

van der Wee N, Rinkel GJ, Hasan D, van Gijn J. Detection of subarachnoid haemorrhage on early CT: is lumbar puncture still needed after a negative scan?. Journal of neurology, neurosurgery, and psychiatry. 1995;58(3):357-9.

Mark DG, Hung YY, Offerman SR, Rauchwerger AS, Reed ME, Chettipally U, Vinson DR, Ballard DW, Kaiser Permanente CREST Network Investigators. Nontraumatic subarachnoid hemorrhage in the setting of negative cranial computed tomography results: external validation of a clinical and imaging prediction rule. Annals of emergency medicine. 2013;62(1):1-10.e1.

Backes D, Rinkel GJ, Kemperman H, Linn FH, Vergouwen MD. Time-dependent test characteristics of head computed tomography in patients suspected of nontraumatic subarachnoid hemorrhage. Stroke. 2012;43(8):2115-9.

Boesiger BM, Shiber JR. Subarachnoid hemorrhage diagnosis by computed tomography and lumbar puncture: are fifth generation CT scanners better at identifying subarachnoid hemorrhage?. The Journal of emergency medicine. 2005;29(1):23-7.

Stewart H, Reuben A, McDonald J. LP or not LP, that is the question: gold standard or unnecessary procedure in subarachnoid haemorrhage?. Emergency medicine journal : EMJ. 2014;31(9):720-3.

Carstairs SD, Tanen DA, Duncan TD, Nordling OB, Wanebo JE, Paluska TR, Theodore N, Riffenburgh RH. Computed tomographic angiography for the evaluation of aneurysmal subarachnoid hemorrhage. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2006;13(5):486-92.

Blok KM, Rinkel GJ, Majoie CB, Hendrikse J, Braaksma M, Tijssen CC, Wong YY, Hofmeijer J, Extercatte J, Kerklaan B, Schreuder TH, ten Holter S, Verheul F, Harlaar L, Pruissen DM, Kwa VI, Brouwers PJ, Remmers MJ, Schonewille WJ, Kruyt ND, Vergouwen MD. CT within 6 hours of headache onset to rule out subarachnoid hemorrhage in nonacademic hospitals. Neurology. 2015;84(19):1927-32.

Perry JJ, Stiell IG, Sivilotti ML, Bullard MJ, Emond M, Symington C, Sutherland J, Worster A, Hohl C, Lee JS, Eisenhauer MA, Mortensen M, Mackey D, Pauls M, Lesiuk H, Wells GA. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. BMJ (Clinical research ed.). 2011;343:d4277.

Ward, M. J., Bonomo, J. B., Adeoye, O., Raja, A. S. and Pines, J. M. (2012), Cost-effectiveness of Diagnostic Strategies for Evaluation of Suspected Subarachnoid Hemorrhage in the Emergency Department. Academic Emergency Medicine, 19: 1134–1144.

Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P ; on behalf of the American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2012;43:1711–1737. | CrossRef |

Steiner T, Juvela S, Unterberg A, Jung C, Forsting M, Rinkel G, European Stroke Organization Guidelines for the Management of Intracranial Aneurysms and Subarachnoid Haemorrhage. Cerebrovasc Dis 2013;35:93-112.

Sidman R, Connolly E, Lemke T. Subarachnoid hemorrhage diagnosis: lumbar puncture is still needed when the computed tomography scan is normal. Acad Emerg Med. 1996; 3:827–31.

Midhun Mohan, Ola Rominiyi, Aswin Chari Chari. Subarachnoid haemorrhage with negative initial neurovascular imaging: a systematic review and meta-analysis of delayed diagnoses and clinical outcomes. PROSPERO 2016 CRD42016035376. | CrossRef | Link |

Dailler F et al. Observational Study of Patients With Subarachnoid Hemorrhage (ProReSHA). WHO, Clinical Trials Registry Platform. NCT02890004. | Link |