- Email: [email protected]
Poor intensive stroke care is associated with short-term death after spontaneous intracerebral hemorrhage
Clinical Neurology and Neurosurgery 191 (2020) 105696
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Poor intensive stroke care is associated with short-term death after spontaneous intracerebral hemorrhage
T
Joana Martineza, Maria Mouzinhoa, Joana Telesa, Patrícia Guilhermeb, Jerina Nogueiraa, Catarina Félixb, Fátima Ferreirab, Ana Marreirosa,c, Hipólito Nzwaloa,c,* a
Faculty of Medicine and Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal Neurology Department, Centro Hospitalar Universitário do Algarve, Algarve, Portugal c Algarve Biomedical Center, Portugal b
A R T I C LE I N FO
A B S T R A C T
Keywords: Intensity of care Outcome Quality of care Mortality Intracerebral hemorrhage
Objectives: The case fatality from spontaneous ICH (SICH) remains high. The quality and intensity of early treatment is one of the determinants of the outcome. We aimed to study the association of early intensive care, using the Intracerebral Hemorrhage–Specific Intensity of Care Quality Metrics (IHSICQM) with the 30-day inhospital mortality in Algarve, Portugal. Patients and Methods: analysis of prospective collected data of 157 consecutive SICH patients (2014–2016). Logistic regression was performed to assess the role of IHSICQM on the 30-day in-hospital mortality controlling for the most common clinical and radiological predictors of death. Receiver operating characteristic (ROC) curve was developed to evaluate the prediction accuracy of the IHSICQM score (C-statistics). Results: forty-five (29 %) patients died. The group of deceased patients had lower intensity of care (lower IHSICQM score) and higher proportion of poor prognosis associated factors (pre-ICH functional dependency, intraventricular dissection/glycaemia). On the multivariate analysis, higher IHSICQM was associated with reduction of the odds of death, 0.27 (0.14-0.50) per each increasing point. The ROC curve showed a high discriminating ability of isolated IHSICQM in predicting the 30-day mortality (AUC = 0,95; 95 % CI = [0,86; 0,95]). Conclusion: the early intensity of quality of care independently predicts the 30-day in-hospital mortality. Quantification of the intensity of SICH is a valid tool to persuade improvement of SICH care, as well to help comparison of performances within and between hospitals.
1. Introduction In contrast to acute ischemic stroke (AIS), the case fatality from spontaneous ICH (SICH) remains high [1]. Part of the SICH prognosis is directly related to limitations of medical treatment, including early donot-resuscitate orders (DNR) practices [2,3]. In fact, studies have shown that avoiding DNR and offering full intensive care in severe SICH decreases mortality and improves the functional outcome [3]. When evaluating the quality of care contribution to the overall acute SICH prognosis, early DNR may be the tip of the iceberg among the continuum of SICH care limitation. For instance, SICH patients may less often receive organized stroke care and allied health interventions in comparison to AIS patients [4]. Despite its relevance, the impact of early limitations of care on SICH prognosis is rarely studied. The
intracerebral Hemorrhage–Specific Intensity of Care Quality Metrics (IHSICQM) punctuates the performance of 26 quality indicators related to 18 facets of acute medical care of patients with SICH [5]. A higher IHSICQM score represents a greater intensity of care which is correlated with lower acute mortality [5,6]. Quantifying the quality of care in SICH is relevant to improve stroke care and to and potentially decrease the associated mortality. We sought to evaluate the impact of the intensity of early SICH care using the IHSICQM on the 30-day in-hospital mortality in a community representative cohort of SICH patients. 2. Material and methods A retrospective analysis of prospective collected data from 2014 to
⁎ Corresponding author at: Faculty of Medicine and Biomedical Sciences and Medicine, University of Algarve, Edifício 7—Ala Nascente- 3° andar Faro, 8005-139 Portugal. E-mail address: [email protected] (H. Nzwalo).
https://doi.org/10.1016/j.clineuro.2020.105696 Received 26 October 2019; Received in revised form 24 January 2020; Accepted 27 January 2020 Available online 30 January 2020 0303-8467/ © 2020 Elsevier B.V. All rights reserved.
Clinical Neurology and Neurosurgery 191 (2020) 105696
J. Martinez, et al.
IHSICQM score between deceased and survivors is shown in Table 2. The group of survivors had significant higher score in every component of IHSICQM with exception of: emergency department evaluation, imaging acquisition, intensive care monitoring, treatment of seizures and gastric ulcer prophylaxis. On the multivariate analysis (Table 3), we observed that per each increasing point of IHSICQM there was a reduction of the odds of death (OR = 0.27, 95 % CI = 0-14-0.50). Other independent predictors of death were the presence of intraventricular dissection (OR = 9.61, 95 % CI = 1.72–17.28) and admission hematoma volume (OR = 17.43, 95 % CI = 2.30–31.78) per additional ml. The ROC curve (Fig. 1) showed a high discriminating ability of isolated IHSICQM in predicting the 30-day mortality (AUC = 0,95; 95 % CI = [0,86; 0,95]).
2016 of consecutive case series of SICH patients, admitted to a single public tertiary hospital serving the Algarve, a well-defined geographical region in southern Portugal. Although no specific institutional guidelines for ICH exist, the treatment decision in all patients admitted with SICH was made by a team consisting of a stroke dedicated physician, a neurosurgeon and an intensivist when necessary. Full details of the study area and data acquisition are described elsewhere [7]. Two authors extracted the relevant information from the mandatory electronic clinical records. Only patients ≥ 18 years, admitted within 6 h of their first ever SICH and treated conservatively were included in the analysis. Medication, physician and nurse’s notes, laboratory results (glycaemia) and radiological findings (hematoma volume, intraventricular dissection, location) were extracted. For each patient, the quality indicators from IHSICQM were compiled systematically, using the original definitions (supplemental material) [5]. The study was approved by the Institutional Ethics Committee. Statistical analysis was performed with SPSS version 23. A significance level of 0.05 was used. Kolmogorov-Smirnov test was used to determine data distribution. Normally distributed variables were analyzed using t-test; non-normally distributed variables were analyzed using Mann-Whitney U test Logistic regression analysis was performed to determine the independent effect of IHSICQM on the 30-day in-hospital mortality taking into account the most important predictors of death in ICH. Receiver operating characteristic (ROC) curve was developed to evaluate the prediction accuracy of the IHSICQM score (C-statistics).
4. Discussion Our study confirmed that the early specific intensity of quality of care, evaluated with the IHSIQM scale, determines the occurrence of short-term death is SICH patients. In comparison to the original study that validated the IHSIQM [5], it’s relevant to mark that our study was performed in a non-academic setting and that it included more than the triple of the original study’s population. The early intensity of care was also controlled for the most relevant prognostic factors such as “prior to SICH functional status”, “hematoma volume”, “presence of intraventricular dissection” and “admission level of consciousness”, reinforcing the scale. For each point increase in the IHSICQM, the chance of dying within the first 30-days of SICH onset reduced (OR: 0.27;0-14-0.50). This quantification stresses the importance of optimizing early care and it’s also valuable as a mean tool to guide strategies to improve prognosis of SICH patients [5,8]. Our study also showed that discrimination of survivors from deceased based on IHSICQM was accurate (AUC = 0.95). In some items however, the overall performance of the quality indications was poor in comparison to findings from the original study that described the IHSICQM [5]. For instance, the proportion of patients complying with parameters that are linked to structural organization such as emergency department evaluation (8 %) and time to imaging (12 %) as well as time to intensive care monitoring initiation (5 %) was overall low and no statistically significant differences were found between survivors and deceased. These items are potentially related to the readiness status, pre-hospital notification or intrahospital stroke code activation, which have been shown to remain problematic in southern Portugal [9]. On the other hand, the lack of specific protocol in our setting also contributes to poor performance in the aforementioned SICH quality of care items. Nevertheless, the group of survivors had consistently better performance in clinical items such the timing of DNR decision and treatment of several specific acute complications. This further confirms that avoiding early limitation of care and taking specific individual interventions such as management of extreme high blood pressure, fever, reversal of coagulopathy or treatment of pneumonia reduces the short-term mortality from SICH [2,3]. Deceased patients had worse performance in items that should be part of the routine care of SICH in the first 2 or 3 days after ictus onset such as dysphagia screening, deep vein thrombosis or enteral nutrition [10], indicating that deceased patients suffer a continuous limitation of care from the admission which reduces the chance of surviving. In most patients the performance evaluation of seizures or status epilepticus recognition and management was not applicable which led to an artificial increase of the proportion of patients with good performance. This should be taken in account when analyzing these two specific items. Furthermore, epilepsy is probably clinically underestimated when routine evaluation is not placed [11] as it is in our and many other settings. Therefore, the results observed for these two items may only be reflecting more severe or clinical obvious seizures. Nevertheless, the use of combined individual metric components
3. Results A total of 159 first ever SICH cases occurred during the study period. Two (1,3 %) were excluded due to lack of information, leaving 157 patients to include in the study. The mean age was 71.75 ( ± 12.03). Ninety-four patients (60 %) were men. Forty-five (29 %) patients died during the first 30 days after hospitalization. Table 1 resumes the comparison between baseline characteristics of deceased and survivors. Deceased patients had lower mean IHSICQM score (15,64 versus 20,65, p < 0.00), higher hematoma volume (34.1 versus 9.3, p < 0.00), higher proportion of intraventricular dissection (20 % versus 3 %, p < 0.00) and higher admission glycaemia (172.8 versus 142.7, p < 0.00). Detailed comparison of each of the items of the Table 1 Comparison of baseline demographic and admission clinical characteristics between survivors and deceased patients. Characteristic
Deceased
Survivors
p-value
Age, mean ± SD Men, n (%) Pre-SICH mRS ≤ 2, n (%) Admission GCS GCS score ≤ 8 GCS score 9-12 GCS score ≥ 13 Hematoma volume, ml, mean ± SD Intraventricular dissection Infratentorial location ICH Score, n (%) 0 1 2 3 4 5 ICH Score, mean ± SD Admission glycaemia (mg/dl) IHSICQM score, mean ± SD
74.71 ± 12.07 25 (56 %) 35 (78 %)
70.56 ± 11.86 77 (69 %) 104 (93 %)
p = 0.05 p = 0.30 p < 0.00 p < 0.00
16 (36 %) 18 (40 %) 11 (24 %) 34.1 (16.7)
6 (5 %) 3 (3 %) 103 (92 %) 9.3 (2.9)
9 (20 %) 15 (33 %)
3 (3 %) 21 (19 %)
0 (0 %) 2 (4 %) 10 (22 %) 14 (31 %) 16 (36 %) 3 (7 %) 3.18 ± 1.01 172.8 ± 55.07 15,64 ± 2,34
31 (28 %) 44 (39 %) 28 (25 %) 6 (5 %) 3 (3 %) 0 (0 %) 1.16 ± 0.98 142.7 ± 58.64 20,65 ± 1,83
p < 0.00 P = 0.01 P = 0.04 p = 0.01
p < 0.00 P = 0.03 p < 0.00
SD:standard deviation; mRS:modified Rankin Score; Pre-SIHC – pre-spontaneous intracerebral hemorrhage; GCS: Glasgow Coma Score; IHSICQM:Intracerebral Hemorrhage–Specific Intensity of Care Quality. 2
102 (91 %) 93 (83 %) 108 (96 %) 93 (83 %) 34 (30 %) 112 (100 %) 108 (96 %) 46 (41 %) 112 (100 %) 109 (97 %) 112 (100 %)
103 (92 %)
138 (88 %) 120 (76 %) 143 (91 %) 115 (73 %) 36 (23 %) 154 (98 %) 130 (83 %) 62 (40 %) 153 (98 %) 136 (87 %) 154 (98 %)
137 (87 %)
109 (97 %)
152 (97 %)
93 (83 %)
111 (99 %)
156 (99 %)
116 (74 %)
111 (99 %)
142 (90 %)
88 (79 %)
109 (97 %) 96 (86 %)
132 (84 %) 124 (79 %)
112 (71 %)
105 (94 %)
139 (89 %)
110 (98 %)
112 (100 %)
146 (93 %)
154 (98 %)
10 (9 %) 11 (9 %) 6 (5 %) 110 (98 %)
13 (8 %) 18 (12 %) 8 (5 %) 127 (81 %)
ED evaluation (performed within 10 minutes of ED arrival) Expedient acquisition of neuroimaging (acquired within 25 minutes of ED arrival) ICU monitoring (initiated within 10 minutes of ED arrival) Time interval between time of ED arrival and DNR or withdrawal of care status (no DNR/withdrawal of care status within 24 h of ED arrival) Time interval between time of ED arrival and DNR or withdrawal of care status (no DNR/withdrawal of care status between 24 h and 7 days of ED arrival) Treatment of acute hypertensive response (achieved target range within 2,5 hours of the second of two consecutive measurements) Early intubation and mechanical ventilation (intubation initiated within 30 min of detection) Treatment of clinically significant intracranial mass effect or transtentorial herniation (clinical reversal of herniation occurring within or ICP value < 20 mm Hg within 60 minutes of detection) Treatment of persistent significant intracranial mass effect or transtentorial herniation (no brain death status within 7 days of herniation or ICP elevation) Treatment of repetitive seizures and status epilepticus (clinical - all motor seizure activity ceased within 20 minutes after the first recorded seizure and there was no return of seizure activity during the next 40 minutes) Treatment of repetitive seizures and status epilepticus (subclinical - all motor and electroencephalographic seizure activity ceased within 20 minutes after the first recorded seizure and there was no return of seizure activity during the next 40 minutes) Treatment of repetitive seizures and status epilepticus (no recurrence of overt or subtle seizure within 12 hours after first seizure) Rapid reversal of elevated INR (1 = INR reversal [INR < 1.4] within 2 hours of first elevated INR > 1.4) Rapid reversal of elevated INR (at least two reversal agents administered within 2 hours of first elevated INR > 1.4) Treatment of elevated serum glucose concentration (target glucose achieved within 4 hours of detection of elevated glucose) Treatment of elevated serum glucose concentration (no recurrent hyperglycemia within 72 hours of admission) Treatment of hyperpyrexia (time to normothermia [first temperature < 37.2 °C] < 4 hours) Treatment of hyperpyrexia (no recurrent hyperpyrexia within 72 hours of admission) Deep venous thrombosis prophylaxis (administration of low molecular weight heparin or heparin in the first 48 hours of arrival) Dysphagia screening (beside evaluation, videofluoroscopic assessment, or fiberoptic endoscopy within 72 hours of arrival) Feeding (nutrition) initiation (enteral feeding started within 72 hours of arrival) Gastric ulcer prophylaxis (H2 blockers, proton blockers, or sucralfate administration in less than 48 hours of symptom onset) Treatment of persistently elevated blood pressure (initiated within 7 days of arrival) Tracheostomy for persistent intubation, or poor airway protection (percutaneous or surgical tracheostomy in less than 7 days of arrival) Treatment of hospital acquired or ventilator associated pneumonia (institution of intravenous antibiotics within 24 hours of first persistent fever documentation [≥38.3 °C on two consecutive measurements recorded 1 hour apart]) Treatment of hospital-acquired or ventilator-associated pneumonia (no new antibiotic substituted or added within 10 days of initiating first antibiotic)
Patients meeting the performance among survivors N(%)
Total patients meeting the performance criteria, N(%)
Variable (threshold for performance)
Table 2 Performance on individualized components of ICH-specific quality of care metrics in patients included in the study.
3
34 (76 %)
42 (93 %)
41 (91 %) 27 (60 %)
22 (49 %) 16 (36 %)
42 (93 %)
35 (78 %) 22 (49 %) 2 (4 %)
27 (60 %)
36 (80 %)
23 (51 %)
24 (53 %)
44 (98 %)
43 (96 %)
45 (100 %)
31 (69 %)
23 (51 %) 28 (62 %)
34 (76 %)
34 (76 %)
3 (7 %) 7 (16 %) 2 (4 %) 17 (38 %)
Patients meeting the performance criteria among deceased N(%)
0,008*
0,022*
0,006* 0,000*
0,000* 0,325
0,022*
0,001* 0,000* 0,000*
0,003*
0,053
0,000*
0,002*
0,640
0,445
0,713
0,000*
0,000* 0,002*
0,002*
0,000*
0,458 0,225 0,586 0,000*
p-value
J. Martinez, et al.
Clinical Neurology and Neurosurgery 191 (2020) 105696
Clinical Neurology and Neurosurgery 191 (2020) 105696
J. Martinez, et al.
higher proportion of functional independent patients in the group of survivors. In conclusion, in a community representative population of SICH patients with different degrees of severity, our study demonstrated that the intensity of quality of care independently predicts the 30-day inhospital mortality. It is of outmost importance to highlight that the parameters used are easy to extract and are part of routine stroke management. The IHSICQM scale can aid comparison of quality of care between hospitals and be used to monitor single hospital performance to drive improvement of SICH care in order to reduce acute mortality.
Table 3 Multivariable analysis of predictors of in-hospital mortality after intracerebral hemorrhage. Characteristic
30-d Death OR (95 % CI)
p Value
IHSICQM (per point) Age (per year) Prior to stroke mRS score ≥3 Intraventricular dissection Admission GCS score (per point) Infratentorial location Admisson hematoma volume (per mL) Admission serum glucose level (per mg/dL)
0.27 (0-14-0.50) 0.95 (0.87–1.02) 1.35 (0.03–3.95) 9.61 (1.72–17.28) 120 (0.95–1.51) 8.76 (0.46–63.81) 17.43 (2.30–31.78) 1.03 (0.90–1.09)
0.00 0.20 0.87 0.01 0.12 0.14 0.00 0,37
CRediT authorship contribution statement Joana Martinez: Conceptualization, Data curation, Formal analysis. Maria Mouzinho: Conceptualization, Methodology. Joana Teles: Conceptualization, Methodology. Patrícia Guilherme: Conceptualization, Data curation, Formal analysis. Jerina Nogueira: Conceptualization, Data curation, Formal analysis. Catarina Félix: Conceptualization, Data curation, Formal analysis. Fátima Ferreira: Writing - review & editing. Ana Marreiros: Conceptualization, Methodology, Writing - review & editing. Hipólito Nzwalo: Writing review & editing. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. References [1] C.J. van Asch, M.J. Luitse, G.J. Rinkel, et al., Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis, Lancet Neurol. 9 (2010) 167–176. [2] J.C. Hemphill, J. Newman, S. Zhao, et al., Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage, Stroke 35 (2004) 1130–1134. [3] L.B. Morgenstern, B.N. Sánchez, M. Geraghty, et al., Full medical support for intracerebral hemorrhage, Neurology 84 (2015) 1739–1744. [4] R. Sheedy, J. Bernhardt, C.R. Levi, et al., Are patients with intracerebral haemorrhage disadvantaged in hospitals? Int. J. Stroke 9 (2014) 437–442. [5] A.I. Qureshi, S. Majidi, Sa. Chaudhry, et al., Validation of intracerebral hemorrhagespecific intensity of care quality metrics, J. Stroke Cerebrovasc. Dis. 22 (2013) 661–667. [6] A.I. Qureshi, Intracerebral hemorrhage specific intensity of care quality metrics, Neurocrit. Care 14 (2011) 291–317. [7] H. Nzwalo, J. Nogueira, A.C. Félix, et al., Short-term outcome of spontaneous intracerebral hemorrhage in Algarve, Portugal: retrospective hospital-based study, J. Stroke Cerebrovasc. Dis. 27 (2018) 346–351. [8] W.C. Ziai, A.A. Siddiqui, N. Ullman, et al., Early therapy intensity level (TIL) predicts mortality in spontaneous intracerebral hemorrhage, Neurocrit. Care 23 (2015) 188–197. [9] S. Sobral, I. Taveira, R. Seixas, et al., Late Hospital Arrival for Thrombolysis after Stroke in Southern Portugal: Who Is at Risk? J. Stroke Cerebrovasc. Dis. 28 (2019) 900–905. [10] Hemphill J.C. 3rd, S.M. Greenberg, C.S. Anderson, et al., Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association, Stroke 46 (2015) 2032–2060. [11] C. Bentes, H. Martins, A.R. Peralta, et al., Post-stroke seizures are clinically underestimated, J. Neurol. 264 (2017) 1978–1985.
Fig. 1. Receiver operator characteristic curves for the prediction of 30-day death using the intracerebral Hemorrhage–Specific Intensity of Care Quality Metrics.
that are time dependent and impact the vital prognosis in different ways reduces the importance of possible problems that may arise in single quality parameters. Moreover, the IHSICQM scale remains an independent risk factor for acute death after controlling for other relevant prognostic factors. This means that the scale is truly dissecting the importance of chain management decisions on the risk of death after SICH. These decisions start before the patient is admitted, for example with pre-hospital notification, and prolongs to the first days of admission, with nutrition or enteral feeding decisions. There are limitations of the present study to be considered. The results are representative of a single region with a specific organization of acute stroke care, which limits generalization. In addition, because of its retrospective nature, the possibility of incomplete or biased documentation is a possibility. A larger sample could have clarified some study findings. For instance, functional disability was not an independent factor for intrahospitalar mortality, despite the finding of
4
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Poor intensive stroke care is associated with short-term death after spontaneous intracerebral hemorrhage
T
Joana Martineza, Maria Mouzinhoa, Joana Telesa, Patrícia Guilhermeb, Jerina Nogueiraa, Catarina Félixb, Fátima Ferreirab, Ana Marreirosa,c, Hipólito Nzwaloa,c,* a
Faculty of Medicine and Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal Neurology Department, Centro Hospitalar Universitário do Algarve, Algarve, Portugal c Algarve Biomedical Center, Portugal b
A R T I C LE I N FO
A B S T R A C T
Keywords: Intensity of care Outcome Quality of care Mortality Intracerebral hemorrhage
Objectives: The case fatality from spontaneous ICH (SICH) remains high. The quality and intensity of early treatment is one of the determinants of the outcome. We aimed to study the association of early intensive care, using the Intracerebral Hemorrhage–Specific Intensity of Care Quality Metrics (IHSICQM) with the 30-day inhospital mortality in Algarve, Portugal. Patients and Methods: analysis of prospective collected data of 157 consecutive SICH patients (2014–2016). Logistic regression was performed to assess the role of IHSICQM on the 30-day in-hospital mortality controlling for the most common clinical and radiological predictors of death. Receiver operating characteristic (ROC) curve was developed to evaluate the prediction accuracy of the IHSICQM score (C-statistics). Results: forty-five (29 %) patients died. The group of deceased patients had lower intensity of care (lower IHSICQM score) and higher proportion of poor prognosis associated factors (pre-ICH functional dependency, intraventricular dissection/glycaemia). On the multivariate analysis, higher IHSICQM was associated with reduction of the odds of death, 0.27 (0.14-0.50) per each increasing point. The ROC curve showed a high discriminating ability of isolated IHSICQM in predicting the 30-day mortality (AUC = 0,95; 95 % CI = [0,86; 0,95]). Conclusion: the early intensity of quality of care independently predicts the 30-day in-hospital mortality. Quantification of the intensity of SICH is a valid tool to persuade improvement of SICH care, as well to help comparison of performances within and between hospitals.
1. Introduction In contrast to acute ischemic stroke (AIS), the case fatality from spontaneous ICH (SICH) remains high [1]. Part of the SICH prognosis is directly related to limitations of medical treatment, including early donot-resuscitate orders (DNR) practices [2,3]. In fact, studies have shown that avoiding DNR and offering full intensive care in severe SICH decreases mortality and improves the functional outcome [3]. When evaluating the quality of care contribution to the overall acute SICH prognosis, early DNR may be the tip of the iceberg among the continuum of SICH care limitation. For instance, SICH patients may less often receive organized stroke care and allied health interventions in comparison to AIS patients [4]. Despite its relevance, the impact of early limitations of care on SICH prognosis is rarely studied. The
intracerebral Hemorrhage–Specific Intensity of Care Quality Metrics (IHSICQM) punctuates the performance of 26 quality indicators related to 18 facets of acute medical care of patients with SICH [5]. A higher IHSICQM score represents a greater intensity of care which is correlated with lower acute mortality [5,6]. Quantifying the quality of care in SICH is relevant to improve stroke care and to and potentially decrease the associated mortality. We sought to evaluate the impact of the intensity of early SICH care using the IHSICQM on the 30-day in-hospital mortality in a community representative cohort of SICH patients. 2. Material and methods A retrospective analysis of prospective collected data from 2014 to
⁎ Corresponding author at: Faculty of Medicine and Biomedical Sciences and Medicine, University of Algarve, Edifício 7—Ala Nascente- 3° andar Faro, 8005-139 Portugal. E-mail address: [email protected] (H. Nzwalo).
https://doi.org/10.1016/j.clineuro.2020.105696 Received 26 October 2019; Received in revised form 24 January 2020; Accepted 27 January 2020 Available online 30 January 2020 0303-8467/ © 2020 Elsevier B.V. All rights reserved.
Clinical Neurology and Neurosurgery 191 (2020) 105696
J. Martinez, et al.
IHSICQM score between deceased and survivors is shown in Table 2. The group of survivors had significant higher score in every component of IHSICQM with exception of: emergency department evaluation, imaging acquisition, intensive care monitoring, treatment of seizures and gastric ulcer prophylaxis. On the multivariate analysis (Table 3), we observed that per each increasing point of IHSICQM there was a reduction of the odds of death (OR = 0.27, 95 % CI = 0-14-0.50). Other independent predictors of death were the presence of intraventricular dissection (OR = 9.61, 95 % CI = 1.72–17.28) and admission hematoma volume (OR = 17.43, 95 % CI = 2.30–31.78) per additional ml. The ROC curve (Fig. 1) showed a high discriminating ability of isolated IHSICQM in predicting the 30-day mortality (AUC = 0,95; 95 % CI = [0,86; 0,95]).
2016 of consecutive case series of SICH patients, admitted to a single public tertiary hospital serving the Algarve, a well-defined geographical region in southern Portugal. Although no specific institutional guidelines for ICH exist, the treatment decision in all patients admitted with SICH was made by a team consisting of a stroke dedicated physician, a neurosurgeon and an intensivist when necessary. Full details of the study area and data acquisition are described elsewhere [7]. Two authors extracted the relevant information from the mandatory electronic clinical records. Only patients ≥ 18 years, admitted within 6 h of their first ever SICH and treated conservatively were included in the analysis. Medication, physician and nurse’s notes, laboratory results (glycaemia) and radiological findings (hematoma volume, intraventricular dissection, location) were extracted. For each patient, the quality indicators from IHSICQM were compiled systematically, using the original definitions (supplemental material) [5]. The study was approved by the Institutional Ethics Committee. Statistical analysis was performed with SPSS version 23. A significance level of 0.05 was used. Kolmogorov-Smirnov test was used to determine data distribution. Normally distributed variables were analyzed using t-test; non-normally distributed variables were analyzed using Mann-Whitney U test Logistic regression analysis was performed to determine the independent effect of IHSICQM on the 30-day in-hospital mortality taking into account the most important predictors of death in ICH. Receiver operating characteristic (ROC) curve was developed to evaluate the prediction accuracy of the IHSICQM score (C-statistics).
4. Discussion Our study confirmed that the early specific intensity of quality of care, evaluated with the IHSIQM scale, determines the occurrence of short-term death is SICH patients. In comparison to the original study that validated the IHSIQM [5], it’s relevant to mark that our study was performed in a non-academic setting and that it included more than the triple of the original study’s population. The early intensity of care was also controlled for the most relevant prognostic factors such as “prior to SICH functional status”, “hematoma volume”, “presence of intraventricular dissection” and “admission level of consciousness”, reinforcing the scale. For each point increase in the IHSICQM, the chance of dying within the first 30-days of SICH onset reduced (OR: 0.27;0-14-0.50). This quantification stresses the importance of optimizing early care and it’s also valuable as a mean tool to guide strategies to improve prognosis of SICH patients [5,8]. Our study also showed that discrimination of survivors from deceased based on IHSICQM was accurate (AUC = 0.95). In some items however, the overall performance of the quality indications was poor in comparison to findings from the original study that described the IHSICQM [5]. For instance, the proportion of patients complying with parameters that are linked to structural organization such as emergency department evaluation (8 %) and time to imaging (12 %) as well as time to intensive care monitoring initiation (5 %) was overall low and no statistically significant differences were found between survivors and deceased. These items are potentially related to the readiness status, pre-hospital notification or intrahospital stroke code activation, which have been shown to remain problematic in southern Portugal [9]. On the other hand, the lack of specific protocol in our setting also contributes to poor performance in the aforementioned SICH quality of care items. Nevertheless, the group of survivors had consistently better performance in clinical items such the timing of DNR decision and treatment of several specific acute complications. This further confirms that avoiding early limitation of care and taking specific individual interventions such as management of extreme high blood pressure, fever, reversal of coagulopathy or treatment of pneumonia reduces the short-term mortality from SICH [2,3]. Deceased patients had worse performance in items that should be part of the routine care of SICH in the first 2 or 3 days after ictus onset such as dysphagia screening, deep vein thrombosis or enteral nutrition [10], indicating that deceased patients suffer a continuous limitation of care from the admission which reduces the chance of surviving. In most patients the performance evaluation of seizures or status epilepticus recognition and management was not applicable which led to an artificial increase of the proportion of patients with good performance. This should be taken in account when analyzing these two specific items. Furthermore, epilepsy is probably clinically underestimated when routine evaluation is not placed [11] as it is in our and many other settings. Therefore, the results observed for these two items may only be reflecting more severe or clinical obvious seizures. Nevertheless, the use of combined individual metric components
3. Results A total of 159 first ever SICH cases occurred during the study period. Two (1,3 %) were excluded due to lack of information, leaving 157 patients to include in the study. The mean age was 71.75 ( ± 12.03). Ninety-four patients (60 %) were men. Forty-five (29 %) patients died during the first 30 days after hospitalization. Table 1 resumes the comparison between baseline characteristics of deceased and survivors. Deceased patients had lower mean IHSICQM score (15,64 versus 20,65, p < 0.00), higher hematoma volume (34.1 versus 9.3, p < 0.00), higher proportion of intraventricular dissection (20 % versus 3 %, p < 0.00) and higher admission glycaemia (172.8 versus 142.7, p < 0.00). Detailed comparison of each of the items of the Table 1 Comparison of baseline demographic and admission clinical characteristics between survivors and deceased patients. Characteristic
Deceased
Survivors
p-value
Age, mean ± SD Men, n (%) Pre-SICH mRS ≤ 2, n (%) Admission GCS GCS score ≤ 8 GCS score 9-12 GCS score ≥ 13 Hematoma volume, ml, mean ± SD Intraventricular dissection Infratentorial location ICH Score, n (%) 0 1 2 3 4 5 ICH Score, mean ± SD Admission glycaemia (mg/dl) IHSICQM score, mean ± SD
74.71 ± 12.07 25 (56 %) 35 (78 %)
70.56 ± 11.86 77 (69 %) 104 (93 %)
p = 0.05 p = 0.30 p < 0.00 p < 0.00
16 (36 %) 18 (40 %) 11 (24 %) 34.1 (16.7)
6 (5 %) 3 (3 %) 103 (92 %) 9.3 (2.9)
9 (20 %) 15 (33 %)
3 (3 %) 21 (19 %)
0 (0 %) 2 (4 %) 10 (22 %) 14 (31 %) 16 (36 %) 3 (7 %) 3.18 ± 1.01 172.8 ± 55.07 15,64 ± 2,34
31 (28 %) 44 (39 %) 28 (25 %) 6 (5 %) 3 (3 %) 0 (0 %) 1.16 ± 0.98 142.7 ± 58.64 20,65 ± 1,83
p < 0.00 P = 0.01 P = 0.04 p = 0.01
p < 0.00 P = 0.03 p < 0.00
SD:standard deviation; mRS:modified Rankin Score; Pre-SIHC – pre-spontaneous intracerebral hemorrhage; GCS: Glasgow Coma Score; IHSICQM:Intracerebral Hemorrhage–Specific Intensity of Care Quality. 2
102 (91 %) 93 (83 %) 108 (96 %) 93 (83 %) 34 (30 %) 112 (100 %) 108 (96 %) 46 (41 %) 112 (100 %) 109 (97 %) 112 (100 %)
103 (92 %)
138 (88 %) 120 (76 %) 143 (91 %) 115 (73 %) 36 (23 %) 154 (98 %) 130 (83 %) 62 (40 %) 153 (98 %) 136 (87 %) 154 (98 %)
137 (87 %)
109 (97 %)
152 (97 %)
93 (83 %)
111 (99 %)
156 (99 %)
116 (74 %)
111 (99 %)
142 (90 %)
88 (79 %)
109 (97 %) 96 (86 %)
132 (84 %) 124 (79 %)
112 (71 %)
105 (94 %)
139 (89 %)
110 (98 %)
112 (100 %)
146 (93 %)
154 (98 %)
10 (9 %) 11 (9 %) 6 (5 %) 110 (98 %)
13 (8 %) 18 (12 %) 8 (5 %) 127 (81 %)
ED evaluation (performed within 10 minutes of ED arrival) Expedient acquisition of neuroimaging (acquired within 25 minutes of ED arrival) ICU monitoring (initiated within 10 minutes of ED arrival) Time interval between time of ED arrival and DNR or withdrawal of care status (no DNR/withdrawal of care status within 24 h of ED arrival) Time interval between time of ED arrival and DNR or withdrawal of care status (no DNR/withdrawal of care status between 24 h and 7 days of ED arrival) Treatment of acute hypertensive response (achieved target range within 2,5 hours of the second of two consecutive measurements) Early intubation and mechanical ventilation (intubation initiated within 30 min of detection) Treatment of clinically significant intracranial mass effect or transtentorial herniation (clinical reversal of herniation occurring within or ICP value < 20 mm Hg within 60 minutes of detection) Treatment of persistent significant intracranial mass effect or transtentorial herniation (no brain death status within 7 days of herniation or ICP elevation) Treatment of repetitive seizures and status epilepticus (clinical - all motor seizure activity ceased within 20 minutes after the first recorded seizure and there was no return of seizure activity during the next 40 minutes) Treatment of repetitive seizures and status epilepticus (subclinical - all motor and electroencephalographic seizure activity ceased within 20 minutes after the first recorded seizure and there was no return of seizure activity during the next 40 minutes) Treatment of repetitive seizures and status epilepticus (no recurrence of overt or subtle seizure within 12 hours after first seizure) Rapid reversal of elevated INR (1 = INR reversal [INR < 1.4] within 2 hours of first elevated INR > 1.4) Rapid reversal of elevated INR (at least two reversal agents administered within 2 hours of first elevated INR > 1.4) Treatment of elevated serum glucose concentration (target glucose achieved within 4 hours of detection of elevated glucose) Treatment of elevated serum glucose concentration (no recurrent hyperglycemia within 72 hours of admission) Treatment of hyperpyrexia (time to normothermia [first temperature < 37.2 °C] < 4 hours) Treatment of hyperpyrexia (no recurrent hyperpyrexia within 72 hours of admission) Deep venous thrombosis prophylaxis (administration of low molecular weight heparin or heparin in the first 48 hours of arrival) Dysphagia screening (beside evaluation, videofluoroscopic assessment, or fiberoptic endoscopy within 72 hours of arrival) Feeding (nutrition) initiation (enteral feeding started within 72 hours of arrival) Gastric ulcer prophylaxis (H2 blockers, proton blockers, or sucralfate administration in less than 48 hours of symptom onset) Treatment of persistently elevated blood pressure (initiated within 7 days of arrival) Tracheostomy for persistent intubation, or poor airway protection (percutaneous or surgical tracheostomy in less than 7 days of arrival) Treatment of hospital acquired or ventilator associated pneumonia (institution of intravenous antibiotics within 24 hours of first persistent fever documentation [≥38.3 °C on two consecutive measurements recorded 1 hour apart]) Treatment of hospital-acquired or ventilator-associated pneumonia (no new antibiotic substituted or added within 10 days of initiating first antibiotic)
Patients meeting the performance among survivors N(%)
Total patients meeting the performance criteria, N(%)
Variable (threshold for performance)
Table 2 Performance on individualized components of ICH-specific quality of care metrics in patients included in the study.
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34 (76 %)
42 (93 %)
41 (91 %) 27 (60 %)
22 (49 %) 16 (36 %)
42 (93 %)
35 (78 %) 22 (49 %) 2 (4 %)
27 (60 %)
36 (80 %)
23 (51 %)
24 (53 %)
44 (98 %)
43 (96 %)
45 (100 %)
31 (69 %)
23 (51 %) 28 (62 %)
34 (76 %)
34 (76 %)
3 (7 %) 7 (16 %) 2 (4 %) 17 (38 %)
Patients meeting the performance criteria among deceased N(%)
0,008*
0,022*
0,006* 0,000*
0,000* 0,325
0,022*
0,001* 0,000* 0,000*
0,003*
0,053
0,000*
0,002*
0,640
0,445
0,713
0,000*
0,000* 0,002*
0,002*
0,000*
0,458 0,225 0,586 0,000*
p-value
J. Martinez, et al.
Clinical Neurology and Neurosurgery 191 (2020) 105696
Clinical Neurology and Neurosurgery 191 (2020) 105696
J. Martinez, et al.
higher proportion of functional independent patients in the group of survivors. In conclusion, in a community representative population of SICH patients with different degrees of severity, our study demonstrated that the intensity of quality of care independently predicts the 30-day inhospital mortality. It is of outmost importance to highlight that the parameters used are easy to extract and are part of routine stroke management. The IHSICQM scale can aid comparison of quality of care between hospitals and be used to monitor single hospital performance to drive improvement of SICH care in order to reduce acute mortality.
Table 3 Multivariable analysis of predictors of in-hospital mortality after intracerebral hemorrhage. Characteristic
30-d Death OR (95 % CI)
p Value
IHSICQM (per point) Age (per year) Prior to stroke mRS score ≥3 Intraventricular dissection Admission GCS score (per point) Infratentorial location Admisson hematoma volume (per mL) Admission serum glucose level (per mg/dL)
0.27 (0-14-0.50) 0.95 (0.87–1.02) 1.35 (0.03–3.95) 9.61 (1.72–17.28) 120 (0.95–1.51) 8.76 (0.46–63.81) 17.43 (2.30–31.78) 1.03 (0.90–1.09)
0.00 0.20 0.87 0.01 0.12 0.14 0.00 0,37
CRediT authorship contribution statement Joana Martinez: Conceptualization, Data curation, Formal analysis. Maria Mouzinho: Conceptualization, Methodology. Joana Teles: Conceptualization, Methodology. Patrícia Guilherme: Conceptualization, Data curation, Formal analysis. Jerina Nogueira: Conceptualization, Data curation, Formal analysis. Catarina Félix: Conceptualization, Data curation, Formal analysis. Fátima Ferreira: Writing - review & editing. Ana Marreiros: Conceptualization, Methodology, Writing - review & editing. Hipólito Nzwalo: Writing review & editing. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. References [1] C.J. van Asch, M.J. Luitse, G.J. Rinkel, et al., Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis, Lancet Neurol. 9 (2010) 167–176. [2] J.C. Hemphill, J. Newman, S. Zhao, et al., Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage, Stroke 35 (2004) 1130–1134. [3] L.B. Morgenstern, B.N. Sánchez, M. Geraghty, et al., Full medical support for intracerebral hemorrhage, Neurology 84 (2015) 1739–1744. [4] R. Sheedy, J. Bernhardt, C.R. Levi, et al., Are patients with intracerebral haemorrhage disadvantaged in hospitals? Int. J. Stroke 9 (2014) 437–442. [5] A.I. Qureshi, S. Majidi, Sa. Chaudhry, et al., Validation of intracerebral hemorrhagespecific intensity of care quality metrics, J. Stroke Cerebrovasc. Dis. 22 (2013) 661–667. [6] A.I. Qureshi, Intracerebral hemorrhage specific intensity of care quality metrics, Neurocrit. Care 14 (2011) 291–317. [7] H. Nzwalo, J. Nogueira, A.C. Félix, et al., Short-term outcome of spontaneous intracerebral hemorrhage in Algarve, Portugal: retrospective hospital-based study, J. Stroke Cerebrovasc. Dis. 27 (2018) 346–351. [8] W.C. Ziai, A.A. Siddiqui, N. Ullman, et al., Early therapy intensity level (TIL) predicts mortality in spontaneous intracerebral hemorrhage, Neurocrit. Care 23 (2015) 188–197. [9] S. Sobral, I. Taveira, R. Seixas, et al., Late Hospital Arrival for Thrombolysis after Stroke in Southern Portugal: Who Is at Risk? J. Stroke Cerebrovasc. Dis. 28 (2019) 900–905. [10] Hemphill J.C. 3rd, S.M. Greenberg, C.S. Anderson, et al., Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association, Stroke 46 (2015) 2032–2060. [11] C. Bentes, H. Martins, A.R. Peralta, et al., Post-stroke seizures are clinically underestimated, J. Neurol. 264 (2017) 1978–1985.
Fig. 1. Receiver operator characteristic curves for the prediction of 30-day death using the intracerebral Hemorrhage–Specific Intensity of Care Quality Metrics.
that are time dependent and impact the vital prognosis in different ways reduces the importance of possible problems that may arise in single quality parameters. Moreover, the IHSICQM scale remains an independent risk factor for acute death after controlling for other relevant prognostic factors. This means that the scale is truly dissecting the importance of chain management decisions on the risk of death after SICH. These decisions start before the patient is admitted, for example with pre-hospital notification, and prolongs to the first days of admission, with nutrition or enteral feeding decisions. There are limitations of the present study to be considered. The results are representative of a single region with a specific organization of acute stroke care, which limits generalization. In addition, because of its retrospective nature, the possibility of incomplete or biased documentation is a possibility. A larger sample could have clarified some study findings. For instance, functional disability was not an independent factor for intrahospitalar mortality, despite the finding of
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