East Practice Management Guidelines Committee

Authors:

William J. Bromberg, MD, chair

Bryan Collier, DO, vice-chair

Larry Diebel, MD

Kevin Dwyer, MD

Michelle Holevar, MD

David Jacobs, MD

Stanley Kurek, DO

Martin Schreiber, MD

Mark Shapiro, MD

Todd Vogel, MD

Scope of the Problem:

            Blunt injury to the carotid or vertebral vessels (blunt cerebrovascular injury – BCVI) is diagnosed in approximately 1/1000 (0.1%) patients hospitalized for trauma in the United States.[1] However the vast majority of these injuries are diagnosed following the development of symptoms secondary to central nervous system ischemia with a resultant neurologic morbidity of up to 80% and associated mortality of up to 40%.[2] When asymptomatic patients are screened for BCVI the incidence rises to 1% of all blunt trauma patients.[3] Key issues that need to be addressed in the diagnosis and management of BCVI include what population (if any) merits screening for asymptomatic injury, what screening modality is best, what is the appropriate treatment for BCVI (both symptomatic and asymptomatic) and what constitutes appropriate follow-up for these injuries.   

Process:

            Identification of references

A computerized search of the National Library of Medicine/National Institute of Health, Medline database was performed utilizing citations from 1965 to 2005 inclusive. The search terms “cerebrovascular trauma,” or “carotid artery” or “vertebral artery” AND wounds and injuries (mesh heading), AND “blunt” limited to the English language returned approximately 1500 citations.  Titles and abstracts were reviewed to determine relevance and isolated case reports, small case series, editorials, letters to the editor, and review articles were eliminated. The bibliographies of the resulting full text articles were searched for other relevant citations and these were obtained when appropriate. One hundred sixty two articles were selected for review and of these 60 met criteria for inclusion and are excerpted in the attached evidentiary table. 

Quality of the references

The Eastern Association for the Surgery of Trauma “Utilizing Evidence Based Outcome Measures to Develop Practice Management Guidelines: A Primer” was utilized as the quality assessment instrument applied to the development of this protocol.[4] Articles were classified as Class I, II, or III according to the following definitions:

            Class I:  Prospective, randomized, controlled trial (there were no Class I articles reviewed)

            Class II: Clinical studies in which the data was collected prospectively, and retrospective analyses which were based on clearly reliable data. Types of studies so classified include: observational studies, cohort studies, prevalence studies, and case control studies. There were 23 Class II studies identified.

            Class III: Studies based on retrospectively collected data. Evidence used in this class includes clinical series, database or registry reviews, large series of case reviews, and expert opinion. There were 37 Class III studies identified. 

Establishment of recommendations

A committee consisting of 10 trauma surgeons was convened to review the data and establish these recommendations using these definitions:[5] 

            Level 1: The recommendation is convincingly justifiable based on the available scientific information alone. This recommendation is usually based on Class I data, however strong Class II evidence may form the basis for a Level 1 recommendation, especially if the issue does not lend itself to testing in a randomized format. Conversely, low quality or contradictory Class I data may not be able to support a Level 1 recommendation.

No Level 1 guidelines were supported by the literature. 

            Level 2: The recommendation is reasonably justifiable by available scientific evidence and strongly supported by expert opinion. This recommendation is usually supported by Class II data or a preponderance of Class III evidence.

Seven Level 2 guidelines were establish by the literature. 

            Level 3: The recommendation is supported by available data but adequate scientific evidence is lacking. This recommendation is generally supported by Class III data. This type of recommendation is useful for educational purposes and in guiding future clinical research.

Nine Level 3 guidelines are proposed for this topic. 

Recommendations 

Question addressed:  What patients should be screened for blunt cerebrovascular injury? 

                                         Level 1: No Level 1 recommendations can be made. 

Level 2:

1.                  Patients presenting with any neurologic abnormality that is unexplained by a diagnosed injury should be evaluated for BCVI.  

2.                  Blunt trauma patients presenting with epistaxis from a suspected arterial source following trauma should be evaluated for BCVI. 

Level 3:

1.                  Asymptomatic patients with significant blunt head trauma as defined below are at significantly increased risk for BCVI and screening should be considered.

Risk factors:

·  GCS ≤8

·  Petrous bone fracture

·  Diffuse axonal injury

·  Cervical spine fracture

·  Fracture through the foramen transversum

·  Lefort II or III facial fractures

2.                  Pediatric trauma patients should be evaluated using the same criteria as the adult population. 

Question addressed: What is the appropriate modality for the screening and diagnosis of BCVI?

Level 1:          No Level 1 recommendations can be made. 

Level 2:         

1.                          Diagnostic four vessel cerebral angiography (FVCA) remains the gold standard for the diagnosis of BCVI.

2.                          Duplex ultrasound is not adequate for screening for BCVI.

3.                          CT angiography with a 4 (or less)-slice multidetector array is neither sensitive nor specific enough for screening for BCVI.  

Level 3:

1.                           Multi-slice (8 or greater) multidetector CTA has the same rate of detection for BCVI when compared to historic control rates of diagnosis with FVCA and should be considered as a screening modality in place of FVCA. 

Question: How should BCVI be treated? This references a grading scheme proposed by Biffl et al.[6]

                        Grading scale

                                    Grade I – intimal irregularity with <25% narrowing

Grade II – dissection or intramural hematoma with >25% narrowing

                                    Grade III – pseudoaneurysm

                                    Grade IV – occlusion

                                    Grade V – transection with extravasation

                        Level 1: No Level 1 recommendations can be made. 

                        Level 2:

1.      Barring contraindications, Grade I and II injuries should be treated with antithrombotic agents such as aspirin or heparin. 

Level 3:

1.      Either heparin or antiplatelet therapy can be used with seemingly equivalent results. A number of authors still recommend heparinization if there is no contraindication, reserving anti-platelet agents for those patients with relative contraindications to heparinization.

2.      If heparin is selected for treatment, the infusion should be started without a bolus and titrated to an aPTT of 50-60 sec.

3.      In patients in whom anticoagulant therapy is chosen conversion to warfarin titrated to a PT INR of 2-3 for 3-6 months is recommended.

4.      Grade III injuries (pseudoaneurysm) rarely resolve with observation or heparinization and invasive therapy (surgery or angio-interventional) should be considered. N.B. carotid stents placed without subsequent anti-platelet therapy have been noted to have a high rate of thrombosis in this population.[7]

5.      In patients with an early neurologic deficit and an accessible carotid lesion operative or interventional repair should be considered to restore flow.

6.      In children who have suffered an ischemic neurologic event, aggressive management of resulting intracranial hypertension up to and including resection of ischemic brain tissue has improved outcome as compared to adults and should be considered for supportive management. 

Question addressed: For how long should antithrombotic therapy be administered? 

                        No recommendations can be made for this question. 

Question addressed: How should one monitor the response to therapy? 

                        Level 1: No Level 1 recommendation can be made.  

                        Level 2:

1.      Follow-up angiography is recommended in Grade I-III injuries. In order to reduce the incidence of angiography-related complications this should be performed after 7 days post injury. 

Level 3: There are no Level 3 guidelines for this question. 

Scientific Foundation:  

Screening and Diagnosis

            Symptomatic patients that undergo FVCA for the indications of unexplained neurologic symptoms or arterial epistaxis the diagnosis of BCVI is made in a significant percentage of cases (38-100%) and is clearly recommended as a reason to pursue the diagnosis.^[8], [9]^, [10]

            Screening asymptomatic patients at risk for BCVI is more controversial. Multiple studies have indicated that patients with BCVI often present hours to days prior to the onset of symptoms.[11]^{, [12], [13]} Failure to identify and treat these injuries can result in significant mortality and morbidity.[14] It is clear that screening for BCVI by essentially any modality can diagnosis BCVI prior to the onset of symptoms at rates up to 10 times higher than previously identified.[15] On the basis of this data a number of individuals recommend screening blunt trauma patients at risk for BCVI using 4-vessel cerebral angiography as the diagnostic modality.[16]^{, [17], [18], [19]} There is some countervailing opinion.

            In a database review of thirty-five thousand patients Mayberry determined that only 17 were diagnosed with BCI of which 11 became symptomatic. Of these only 2 were asymptomatic for over 2 hours post admission, and of these 2, only 1 met criteria for screening. Based on this data Mayberry et al concluded that screening was futile in light of the inability to diagnose the injury prior to the development of symptoms.[20]  The majority of the available data does not support this finding. The preponderance of the evidence supports the recommendation that patients at risk for BCVI can be identified and diagnosed prior to the onset of symptoms with the application of an appropriate screening modality. 

Criteria for screening/Risk factors

            The mechanism of BCVI seems to be associated with cervical hyperextension and rotation, hyperflexion, or direct blow.[21] The factors that are most closely associated with the finding of BCVI are direct evidence of neurologic deficits as noted above. In asymptomatic patients a number of factors have been associated with increased risk of BCVI. Biffl and colleagues performed linear regression analysis of a liberally screened patient population (N =249)and found that there were four independent risk factors for BCAI. These were: 1) GCS<6, 2) Petrous fracture, 3) Diffuse axonal injury, and 4) LeFort II or III fracture. Patients who had one risk factor had a risk of 41% for BCAI. This risk increased to 93% in the presence of all 4 factors. The only risk factor for BVAI was presence of cervical spine fracture. However 20% of patients diagnosed with BCVI selected for screening by the criteria in Table 1 did not have the independent risk factors identified by regression analysis indicating that broad selection criteria are necessary to prevent missed injuries.[22] Cothren retrospectively reviewed patients with BVAI and found that complex cervical spine fractures involving subluxation, fracture into the foramen transversarium, or C1 to C3 fractures were closely associated with this injury.[23]  In a prospective review of screening with DFVCA Cothren et al utilized criteria similar to that proposed by Biffl and modified to incorporate those specific cervical spine fracture patterns shown to increase risk of BVAI to select patients for evaluation (Table 2). Seven hundred and twenty-seven patients (4.6%) of all blunt trauma patients were studied and 244 were diagnosed with BCVI for a screening yield of 34%.[24] An isolated cervical seat belt sign without other risk factors and normal physical exam has failed to be identified as an independent risk factor in two retrospective studies and should not be utilized as the sole criteria to stratify patients for screening.[25]^, [26]

Table 1

Screening Criteria for BCVI adapted from Biffl et al9 (with permission)

Table 2

Denver Modification of Screening Criteria for BCVI adapted from Cothren et al59 (with permission) 

Screening Modality

Duplex Sonography

            Multiple studies have shown that duplex sonography is not sensitive enough for screening for BCVI with an overall sensitivity from as low as 38.5%[27] to as high as 86% (the latter for carotid injuries alone).[28]^, [29] Duplex US cannot be recommended as a screening modality for BCVI. 

Angiography

            Arguments have been made that DFVCA, in an appropriate group is safe, sensitive, and cost effective. Biffl et al report a 27% rate of positive screening angiogram when asymptomatic patients were screened according to the criteria in Table 1.[30] Cothren[31] utilized DFVCA in 727 asymptomatic patients that met screening criteria (Table 2) in which he found 244 patients with injury (34% screening yield). In patients who were initially asymptomatic and could not have antithrombotic therapy there was a 21% (10/48) rate of ischemic neurologic event (INE) whereas in those treated with either heparin, low molecular weight heparin, or antiplatelet agents only one of 187 had an INE.  Using this internal data Cothren estimated that the identification and treatment of asymptomatic BCVI in these 187 patients prevented 32 strokes. This comes at an expense (charge data) of $6500 per angiogram for a total of approx. $154 000 per stroke avoided. Cothren concludes that this is cost-effective and screening with DFVCA should be pursued. The argument against the utilization of DFVCA (aside from that against screening per se) is that it is expensive (approx $1500)[32], carries an inherent risk of stroke (1-2%)[33] and is impractical to apply at many institutions.[34]  

Magnetic Resonance Angiography

            In so far as MRA is non-invasive and requires no contrast administration MRA/MRI has been gaining popularity as an alternative to DFVCA for the diagnosis of BCVI. Although a number of studies describe the use of MRA to identify BCVI [35]^, [36]^, [37]^, [38] at this time the few direct studies that do exist indicate that sensitivity and specificity is significantly lower than that of DFVCA. In a (albeit small) direct comparison of MRA vs. angiography Miller et al found a sensitivity of 50% for CAI and 47% for VAI.[39] Levy also reported a significantly lower sensitivity for MRI and MRA than angiography for the diagnosis of BCVI.[40] It seems that, based on this data MRA cannot be recommended as the sole modality for the screening of BCVI. 

Computed Tomographic Angiography

            Early CT angiography with 1 to 4 slice scanners is not sensitive enough to qualify as an adequate screening modality for BCVI. In a prospective study of CTA on a single slice scanner vs. DFVA Biffl et al report a sensitivity and specificity of 68% and 67% respectively.[41] Similarly Miller et al compared 4-slice CTA vs. DFVCA and showed that CTA performed poorly with a sensitivity of 47% for CAI and 53% for VAI.[42] Sensitivity and specificity seems to improve in direct relationship to improvements in technology, however. In a prospective study which included images obtained from single, four and eight-slice scanners Bub reports improvement in image quality and concomitant improvement in sensitivity and specificity as the number of detectors increases. The overall results for the mixed population (reported as ranges from different observers) was 83-92% sensitivity and 88-92% specificity for the carotid artery and 50-60% sensitivity and 90-97% specificity for the vertebral artery.[43] Berne et al screened patients with 4-slice and, later, 16-slice scanner CTA in a study in which only positive CTA studies underwent confirmatory angiography showing an overall sensitivity (for symptomatic BCVI) and specificity of 100% and 94% respectively. Interestingly the incidence of BCVI detected went up from 0.6% with the earlier machine to 1.05% with the newer device, approaching historic incidence of BCVI as diagnosed by DFVCA and the comparative specificity improved from 90.8% to 98.7%.[44] In a follow-up study Berne et al screened patients for BCVI solely with a 16-slice scanner. In this prospective study Berne showed that the detected incidence of BCVI goes up threefold when changing from a 4-slice scanner to a 16-slice scanner with a resulting incidence of 1.2% which is similar to that found by screening with DFVCA.[45] In a similar study in which only positive 16-slice CTA studies were followed by DFVCA, Biffl et al reversed an earlier recommendation[46] that CTA was not adequate for screening for BCVI reporting a sensitivity of 100% for symptomatic BCVI.[47] Schneidereit and colleagues report similar findings and give a diagnosed incidence for BCVI of 1.4% using a 16-slice scanner.[48] Although these studies are interesting obviously a true sensitivity can only be obtained via direct comparison between CTA and DFVCA. At this time only one study has directly compared 16-slice CTA vs. angiography for screening for BCVI. Eastman et al performed 162 CTAs followed by 146 confirmatory DFVA studies (12 patients refused consent, 4 were discharged, and 6 died of non-neurologic causes prior to the study being obtained). Twenty carotid injuries and 26 vertebral artery injuries were identified with one false negative CTA (a grade I vertebral artery injury) for a screened population incidence of 28.4% and an overall incidence of 1.25%. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 97.7%, 100% 100%, 99.3%, and 99.3% respectively.[49]

Blunt cerebrovascular injuries in children: There is a relative paucity of information on the screening, diagnosis, and management of BCVI in children and what is available primarily consists of isolated case reports and small case series. In one review of the National Pediatric Trauma Registry (NPTR) Lew and colleagues found an overall incidence of 0.03%, which is lower than that of the adult trauma population and speculated that it may be due to the increased elasticity of the younger children’s blood vessels. They did note that another possibility was that the difference was secondary to decreased detection in children and the retrospective nature of the study. Children under six years of age seemed to be at higher risk, making up 73% of patients with BCVI whereas they made up only 36% of the registry patients. Chest trauma (in particular clavicle fracture) and severe head injury (basilar skull fracture, intracranial hemorrhage) were associated with a higher risk of BCVI in the pediatric population.[50] In a case review of 5 patients with BCI Duke and Partington[51] recommend initial treatment of the arterial injury to be the same as in adults. Where recommendations differ is that they go on to recommend aggressive management of intracranial hypertension in children up to and including resection of infracted tissue due to improved outcome in pediatric patients in contradistinction to the dismal outcome of post-ischemic intracranial hypertension in adults. 

Treatment of BCVI

            Surgery – a number of studies from the 80’s and 90’s have concluded that if individuals have minimal or no symptoms and an accessible carotid lesion they do well with operative intervention and therefore recommend repair of any more than minor intimal irregularities.[52]^,[53],[54] However most of these studies also note that if patient present with profound neurologic deficit, revascularization does not improve outcome. In all studies that have compared ligation v. repair, those patients that do not have a profound deficit do much better with repair.[55]^{, [56]} Karlin for example found a 7.8% mortality in patients undergoing repair v. 50% in those undergoing ligation and that, furthermore, those patients who did not have a deficit prior to surgery did not develop one if revascularized.[57] Finally a vast majority of these studies including Richardson[58] indicate that if the patient presents with a dense neurologic deficit, neither operation nor anticoagulation improves outcome. All of these studies however were of Class III quality. 

            Anticoagulation – there have been a number of studies attempting to evaluate the impact of antithrombotic agents on the progression or development of sequellae of BCVI. As is not unexpected the results have been somewhat contradictory but the weight of the evidence seems to support the administration of antithrombotic agents to those patients with BCVI who do not have contraindications for such. A series of retrospective studies[59]^{, [60], [61], [62]} found that administration of antithrombotic agents reduces the rate of neurologic sequellae after BCVI. Fabian also indicated that mortality also improves with heparinization in this population.  Although there has not been a direct, controlled comparison of heparinization vs. antiplatelet agents (aspirin or clopidigrel) in the prevention of CVA after BCVI, a number of studies performed subgroup analysis in an attempt to address this question. In one of these studies Biffl[63] compared those patients treated with ASA v. heparin and found a trend towards reduction in CVA for those treated with heparin (1% v. 9% p=0.07) however in studies by Wahl,[64] Cothren,[65] and a second study by Biffl,[66] failed to demonstrate a difference in outcome between the two modalities. In these previously mentioned studies both Cothren and Biffl still recommend heparinization as first line therapy for those patients without contraindications, reserving antiplatelet agents for those not deemed to be candidates for anticoagulation.

            Serious bleeding complications can accompany aggressive anticoagulation regimens. In a mixed population of patients with both blunt and penetrating carotid injury Nanda[67] found that, in patients with a pre-existing intra-cerebral hemorrhage, anticoagulation resulted in worsening in 2/3. Extracranial hemorrhage is another frequent complication of systemic heparinization in polytrauma patients. For example in a previously mentioned study Biffl[68] noted that bleeding which required either transfusion or cessation of heparin was encountered in 54% of patients prompting him to recommend a conservative protocol for the initiation and maintenance of the heparin infusion and tight control of aPTT to within 40-50 seconds in a later study.[69]

             Angiointerventional therapy – There have been several preliminary, Class III studies that have indicated the safety and feasibility of catheter directed therapy to include embolization of pseudoaneurysms and stenting of intimal injuries.[70]^{, [71], [72], [73]} A more recent Class II study by Cothren[74] indicated that the carotid artery occlusion rate in patients who underwent stenting is much higher than that of patients with BCAI who were treated with antithrombotic agents alone. This resulted in a rate of complications (3 CVA and one subclavian artery dissection) of 21% in stented patients v. 5% in non-stented patients (no one who was received anticoagulation suffered a CVA). The author goes on to add that the reason for this may be that patients who had undergone stenting were then treated with heparin and not anti-platelet agents and recommends a study to evaluate this.

             Monitoring response to therapy – In a Class II study, Biffl[75] found that follow-up angiography changes management in 61% of BCVI, particularly in that Grade 1 and 2 injuries often go on to complete healing or to form a pseudoaneurysm within 7-10 days. The author went on to note that the complication rate of angiography was significantly higher if the follow-up procedure was performed within 7 days and recommends that at least that amount of time be allowed to lapse prior to follow-up angiography.

 Future Directions. 

            Screening – Blunt cerebrovascular injury is a rare entity (though not as rare as formerly thought), which requires a high index of suspicion to identify prior to the onset of symptoms. The clinical and cost-effectiveness of a screening program depends on both disease-specific, test specific, and organizational issues as well as the utility (or futility) of the treatment modalities available. Further prospective investigation is necessary to further refine the screening criteria so as to maximize the disease incidence in the screened population which will increase accuracy and decrease costs.

             Treatment – the optimum modality for the treatment of BCVI is as yet undetermined. Prospective studies will be necessary to compare invasive intervention v. anticoagulation. Furthermore the optimal anticoagulation regimen is as yet unknown in terms of agent (anti-platelet v. heparinoid v. warfarin) as well as the duration and endpoint of therapy. Cleary there is room for further study in this regard. In light of the relative rarity of the disease entity, systematic, multi-institutional studies will be required to answer this question.  

Evidentiary Table