Probability assessment of intracerebral hemorrhage in prehospital emergency patients

The term stroke derives from the sudden onset of neurological deficits but includes heterogeneous subtypes of acute ischemic stroke (AIS), intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) [1, 2]. Some therapeutic approaches, such as antithrombotic/thrombolytic treatment, are indicated in AIS patients but are contraindicated in ICH patients. In contrast, acute blood pressure lowering is regularly used in ICH patients to reduce early hematoma growth [3] while such therapy is generally not recommended in AIS patients. Certain clinical features were found to be associated with higher likelihood of ICH and were used to develop clinical decision scores to discriminate between ICH and AIS patients [4], but diagnostic accuracy was rather low [5]. Therefore, ICH can only be reliably diagnosed or excluded by cerebral imaging (computed tomography [CT] or magnetic resonance imaging [MRI]), usually only available in hospitals. Mobile stroke units (MSUs) with imaging capabilities on board offer stroke subtype differentiation in the prehospital setting [6‐8].

The use of MSUs has spread in several countries, but they are not yet available in most areas worldwide [9, 10]. Therefore, a prehospital probability estimation of ICH or AIS is based on patient characteristics and clinical examination. Because some time-sensitive interventions like systemic thrombolysis alone or in combination with mechanical thrombectomy [11‐13] or neurosurgical operations are only available in specialized hospitals, the differentiation between ICH and AIS patients is clinically relevant to make the correct transport decision to the nearest and most appropriate hospital. Otherwise, secondary transfers from non-specialized hospitals are required, thereby delaying treatment and possibly worsening prognosis.

We aimed at developing and validating a simple clinical decision score, called prehospital-intracerebral hemorrhage (ph-ICH) score, that can be used by paramedics with limited training in neurological examination. Frequently, only limited data are available on previous medical conditions and medication of individual patients in the prehospital setting and usually no prehospital cerebral imaging capabilities are available. Therefore, the ph-ICH score was constructed as a simple prehospital multidimensional score assessing and considering only a few easily obtainable and measurable clinical variables in the absence of cerebral imaging data. This risk stratification ph-ICH score should assist but not replace the prehospital diagnostic steps – depending on certain threshold values – in assessing the probability of ICH and AIS.

A total of 1400 STEMO alarms were evaluated, and 416 patients were identified with complete documentation in the derivation cohort, as shown in the Flow Chart (Fig. 1). AIS was diagnosed in 224 (53.9%), SM in 119 (28.6%), TIA in 41 (9.9%) and ICH in 32 (7.7%) patients. For the validation cohort, we analyzed data of 252 AIS (88.4%) and 33 ICH (11.6%) patients (285 patients overall). The baseline demographics can be found in Table 1 and Table 1 of the Supplement.

The ph-ICH score showed significant higher mean average scores for ICH compared to the AIS group (derivation cohort: 1.8 ± 1.2 vs. 1.0 ± 0.9, d = 0.9, p < 0.01; validation cohort: 1.8 ± 0.9 vs. 0.8 ± 0.7 points, d = 1.4, p < 0.01). The ph-ICH scores were lower in the SM (derivation cohort: 0.6 ± 0.7 points) and TIA group (derivation cohort: 0.4 ± 0.6 points).

The specificity, PPV and LR+ were positively and the sensitivity was negatively correlated with increasing ph-ICH scores in the AIS group, as indicated in Table 3B and C. Increasing ph-ICH scores increased the likelihood that a patient suffers from an ICH and not an AIS. When evaluating certain threshold values, ph-ICH scores of greater than 1.5, 2.0, 2.5, 3.0 and 3.5 showed a likelihood for an ICH, i. e. a PPV of 0.21, 0.24, 0.45, 0.47, 0.8 and 0.34, 0.46, 0.62, 1.00, 1.00 for the derivation and validation cohort (Table 3B and C), respectively.

The ICH patients presented with higher first measured SP and DP compared to the group of AIS patients in the derivation cohort (mean average: 197 ± 34/110 ± 28 vs. 164 ± 32/94 ± 23 mmHg, d = 1.0 and 0.7, both p < 0.01) and validation cohort (mean average: 189 ± 35/104 ± 29 vs. 163 ± 31/87 ± 18 mmHg, both d = 0.9 and p < 0.01). Accordingly, a higher relative number of patients showed a SP ≥ 180 mmHg and DP ≥ 110 mmHg (derivation cohort: 65.6 vs. 32.1% and 31.3 vs. 18.8%, p < 0.01 and p = 0.1; validation cohort: 60.6 vs. 32.9% and 42.4 vs. 9.9%, both p < 0.01).

Stroke severity was higher in the ICH group compared to the AIS group (derivation cohort: median NIHSS sum score: 15 (Q₁-Q₃ = 7–22, IQR = 15) vs. 7 (Q₁-Q₃ = 4–16, IQR = 12); validation cohort: median NIHSS sum score: 15 (Q₁-Q₃ = 7–19, IQR = 12) vs. 6 (Q₁-Q₃ = 3–12, IQR = 9)). Accordingly, a higher relative number of ICH patients showed an NIHSS sum score ≥ 10 (derivation cohort: 59.4 vs. 40.2%, p = 0.04; validation cohort: 69.7 vs. 30.2%, p < 0.01) and ≥ 15 (derivation cohort: 50.0 vs. 25.9%, p = 0.01; validation cohort: 51.5 vs. 17.5%, p < 0.01) compared to AIS patients. SM patients presented with lower NIHSS sum scores than AIS patients and TIA patients presented with the lowest NIHSS sum scores. More ICH patients showed a decrease in level of consciousness.

Similar proportions of patients with a history of arterial hypertension were found in the ICH and AIS group (derivation cohort: 81.3 vs. 77.2%, p = 0.61; validation cohort: 93.9 vs. 83.3%, p = 0.11) while atrial fibrillation was found less often in the derivation cohort for the ICH group (derivation cohort: 18.8 vs. 42.0%, p = 0.01). Overall, 25 seizures were reported in the SM and two in the AIS group.

ICH and AIS patients require very different, frequently highly time-critical, medical interventions, often only available in certain specialized hospitals. Therefore, clinical prediction scores were developed to assess the likelihood of an ICH and AIS based on clinical judgement [19]. The Siriraj Stroke Score – based on eight items and tested in small studies with a limited number of patients – seems to lack positive predictive value for both ICH and AIS patients [20, 21]. Other authors report a higher validity for decision scores, but require prerequisites usually not available in prehospital care like the neurological assessment of the patient after 3 hours and paraclinical variables (white blood cell count) [22]. Other authors conclude, that the Siriraj and Guy’s hospital stroke score [5] and the Allen score [23] also lack accuracy in distinguishing ICH from AIS patients.

Here, we developed a prehospital decision score, called ph-ICH score, to assess the likelihood of ICH or AIS patients with certain requirements: a) the score is easy to calculate with only a limited number of variables, b) can be performed without extensive neurological knowledge and c) does not require information about pre-existing conditions of the patient.

SP ≥ 180 mmHg and the level of consciousness≥1 (one point for each item) as two dichotomous variables can be easily determined and were different between ICH and AIS patients and were therefore included in the ph-ICH score. The single NIHSS item level of consciousness was particularly investigated, because a reduced level of consciousness is often reported to be more likely in ICH than AIS patients [4].

Furthermore, for reasons of simplicity, we chose the single items of the NIHSS that most likely can be performed by non-neurological specialists and showed significant differences between ICH and AIS patients. We developed this “short NIHSS” comprising vigilance, following commands, visual field, motor weakness of an arm or leg as well as sensory disturbances with data from the derivation cohort und validated this score within the ph-ICH score in the validation cohort. The “short NIHSS” variables showed significant differences between ICH and AIS patients and may be assessed by non-neurological personnel without extensive training in neurological examination. The ph-ICH score was calculated as the sum of the dichotomous variables SP ≥ 180 mmHg, level of consciousness≥1 (1 point for each item) and the sum of the “short NIHSS”. SP and level of consciousness were used as dichotomous variables for reasons of simplicity. To adjust the “short NIHSS” to the level of blood pressure and level of consciousness, the sum was divided by ten, as shown in Table 3. We did not include atrial fibrillation in the ph-ICH score, because it requires information about pre-existing conditions which may not always be available in the prehospital setting. However, if available in the field, the presence of atrial fibrillation may additionally be used to assess the likelihood of ICH or AIS.

The likelihood of suffering from an ICH rises with increasing ph-ICH scores (Table 3). Because the paramedics do not know for certain whether the patient with a suspected CVD suffers from an ICH, AIS, TIA or SM, we additionally compared the ICH with the AIS/TIA/SM group. In this comparison, when choosing certain threshold scores of greater than 1.5 and especially 3.0, the likelihood of an ICH steeply rises with increasing values, as reflected in the PPV and positive likelihood ratio.

Although the PPV, likelihood ratio and relative number of patients for ICH is very high above certain threshold values (≥3.0), the low prevalence of an ICH is resulting in a similar absolute number of patients (9 vs. 8 patients, Table 3B), because the PPV depends on the prevalence of a disease.

Similar results were found when comparing the differences of the ph-ICH score between the ICH and AIS group as well as the ICH and AIS/TIA/SM group (Table 3).

The ROC curve performed fair and good with an AUC of 0.71 and 0.81 (Fig. 2).

In addition to the above mentioned variables, a number of clinical findings have been reported to increase the likelihood of an ICH compared to an AIS diagnosis such as coma, neck stiffness, seizures accompanying the neurologic deficit, DP > 110 mmHg, vomiting and headache [4]. On average, patients with ICH present with more severe neurological deficits [24].

These results are in line with our findings of higher SP and DP, higher proportion of patients with an impaired consciousness and more severe neurological deficits, i. e. higher median NIHSS sum scores. Because neck stiffness, vomiting and headache were not documented in a standardized manner, these variables were not investigated in this study.

Seizures are often mimicking a CVD and in a study of our group 21% of SM patients had seizures [17]. Most seizures in this study were also found in the SM group (25 patients, 92.6%).

Certain limitations must be considered. First, our analysis was conducted retrospectively on already existing study data with no monitoring, possibly leading to some data abstraction inaccuracies. Second, the ph-ICH score was not actually applied by the emergency medical personnel in the field, but retrospectively calculated and tested. Third, in the validation cohort we were only able to compare ICH to AIS patients. Fourth, the number of AIS patients was considerably larger than the number of ICH patients. The possibility that the results of the ICH groups were found by chance was larger than in the AIS groups. Furthermore, the PPV is dependent on the prevalence of a disease. Fifth, the data of our study was obtained in a highly standardized manner by specialized personnel with extensive experience in the treatment of patients with CVD. Although the ph-ICH-score was developed as a simple tool for paramedics, the generalizability of our results in settings with non-specialized personnel needs to be examined in further studies.

In summary, ICH compared to AIS patients presented with higher ph-ICH scores and thereby with more severe strokes and higher first measured blood pressures. TIA and SM patients presented with even lower ph-ICH scores and first measured blood pressures than AIS patients. Especially very high values of at least 3.0 and 3.5, increase the likelihood of an ICH over an AIS. The differentiation between ICH and AIS is important, because these patients often require highly time-critical interventions, only available in certain hospitals.

Future larger prospective studies are necessary to investigate whether the ph-ICH score helps to improve the transport decision by emergency medical personnel and thereby improve the outcome of patients.