We enrolled 3132 patients, including 240 (7.7%) with confirmed subarachnoid haemorrhage, from among 5424 potentially eligible patients with headache who presented to the study sites during our study (figure).
Flow and follow-up of patients in study of computed tomography for diagnosis of subarachnoid haemorrhage
Tables 1 and 2 list the characteristics of our study cohort. Overall, patients were young (mean age <45), most (82%) characterised the headache as being their worst ever, a quarter arrived by ambulance, half underwent lumbar puncture after negative results on computed tomography, and 240 (7.7%) had subarachnoid haemorrhage. In 27 (0.9%) patients the diagnosis was serious: 17 (0.5%) had other haemorrhagic strokes, nine (0.3%) had a brain tumour, and one (0.03%) had bacterial meningitis.
Table 1 Characteristics of 3132 enrolled patients with acute headache in study of computed tomography for diagnosis of subarachnoid haemorrhage. Figures are numbers (percentage) of patients unless stated otherwise
Table 2 Management and outcomes of 3132 patients with acute headache in study of computed tomography for diagnosis of subarachnoid haemorrhage
For all study patients, the sensitivity of computed tomography overall was 92.9% (95% confidence interval 89.0% to 95.5%), the specificity was 100% (99.9% to 100%), the negative predictive value was 99.4% (99.1% to 99.6%), and the positive predictive value was 100% (98.3% to 100%) (table 3). In four additional patients, classified as not having subarachnoid haemorrhage, the initial computed tomogram indicated an aneurysm without haemorrhage, and they underwent angiography. One patient with a giant aneurysm (>25 mm) underwent surgery for the aneurysm, and the three others (aneurysm size 2-5 mm) were managed conservatively. The sensitivity was 100% (97.0% to 100.0%) for subarachnoid haemorrhage in the 953 patients in whom computed tomography was performed within six hours of headache onset, with a specificity of 100% (99.5% to 100%), a negative predictive value of 100% (99.5% to 100%), and a positive predictive value of 100% (96.9% to 100%) (table 3). When computed tomography was performed more than six hours after headache onset, 17 of 119 patients with subarachnoid haemorrhage were not identified by unenhanced computed tomography (sensitivity 85.7%, 78.3 to 90.9%). For these 17 patients with a false negative result, computed tomography was performed from eight hours to eight days after the onset of headache. Of these 17 patients, 13 were diagnosed by xanthochromia in the cerebrospinal fluid on visual analysis and two by red blood cells in the final tube of cerebrospinal fluid with abnormal cerebral angiography. One patient had negative results on computed tomography 96 hours after the onset of headache without lumbar puncture; the patient returned to the emergency department and repeat computed tomography showed a new subarachnoid haemorrhage secondary to vertebral artery dissection. Another patient had an aneurysm identified, without subarachnoid haemorrhage, on the unenhanced computed tomogram; this was confirmed with angiography and it subsequently bled while the patient was awaiting surgery. Only six of these 17 underwent neurosurgical intervention (ventricular drain, aneurysm coiling or clipping). Of the 11 remaining cases, no cause for bleeding was found in 10, and one other was thought to have bleed secondary to a brain tumour. One patient with no source of bleeding identified had a 5 mm middle cerebral artery aneurysm, thought to be incidental, and the patient was alive and well at six months with conservative management.
Table 3 Sensitivity of computed tomography for subarachnoid haemorrhage in patients with acute headache stratified by timing of scan
There were 1931 patients requiring follow-up. Of these we contacted 1506 patients by telephone six months or more after their initial emergency visit; none was identified as having had subarachnoid haemorrhage. Of the remainder, we identified eight patients who died within six months after their index visit, all from other causes: five from cancer, one from pneumonia, one from an ischaemic stroke, and one presumed cardiac (patient had had a previous myocardial infarction and died 32 days after their visit for headache, but four days after a visit for chest pain; no autopsy was performed). Fifty patients (13 in the group who underwent computed tomography within six hours) could not be reached by telephone and had no subsequent hospital visits. None of these patients was seen at the regional neurosurgical referral centre within six months of the index visit, and they have been classified as negative for subarachnoid haemorrhage. For 31 of these patients, at the five Ontario sites, we were able to search provincial coroner reports. None of the 31 lost to all follow-up had reportedly died suddenly and unexpectedly in the province.
In our study, emergency physicians initially misinterpreted the computed tomography as normal in three cases and discharged these patients home. These three patients were recalled after review of the imaging by radiologists. All three underwent computed tomography more than six hours after the onset of headache. Another computed tomogram was also initially misinterpreted as normal by both the emergency physician and a radiology trainee. This patient presented four and a half hours after the onset of headache, had blood in the cerebrospinal fluid (632
/L in the fourth tube) attributed to a traumatic lumbar puncture by a neurosurgical trainee, and was found to have an aneurysm on follow-up magnetic resonance imaging angiogram five days later. In retrospect, the local neuroradiologist re-interpreted the initial scan as positive for subarachnoid haemorrhage. The patient underwent coiling and had a good clinical outcome.
Because many patients did not undergo lumbar puncture, we conducted a post hoc subgroup analysis of patients who underwent lumbar puncture versus those who did not. There was no significant difference in sex, loss of consciousness, arrival by ambulance, onset with exertion, vomiting, mean blood pressure, or heart rate. There were differences in mean age (higher chance of lumbar puncture in younger patients (mean age 47.1 v 43.0), time to peak pain intensity (if faster peak (mean 5.7 v 9.4 minutes)), neck pain (if present (39.0% v 34.9%)), and being characterised as the “worst headache ever” (if present (91.6% v 76.3%)) between the lumbar puncture and the no lumbar puncture groups.
There were 2292 eligible patients who were potentially eligible but were not enrolled because no data form was completed. This group of patients had similar characteristics to enrolled patients (mean age 45.3; 60% women), and there were 137 subarachnoid haemorrhages (6%). Of these, 67 patients with subarachnoid haemorrhage underwent computed tomography within six hours; all 67 had subarachnoid blood identified on unenhanced computed tomography.