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Timing of Low-Dose Aspirin Discontinuation and the Influence on Clinical Outcome of Patients Undergoing Surgery for Chronic Subdural Hematoma
Original Article
Timing of Low-Dose Aspirin Discontinuation and the Influence on Clinical Outcome of Patients Undergoing Surgery for Chronic Subdural Hematoma Alba Scerrati1, Antonino Germano`2, Gianluca Trevisi3, Jacopo Visani1, Giorgio Lofrese4, Luca D’Angelo1, Giovanni Raffa2, Elena Fazzari2, Annunziato Mangiola3, Michele Alessandro Cavallo1, Pasquale De Bonis1
BACKGROUND: An appropriate time (5e7 days) of discontinuation of low-dose acetylsalicylic acid (ASA) in patients undergoing surgery for chronic subdural hematoma (CSDH) is recommended. However, patient clinical deterioration often does not allow to wait the recommended time for surgery. Clear guidelines regarding the perioperative management of patients with ASA therapy are still lacking. The aim of this study is to compare the surgical outcome, complications, and mortality of patients suffering from CSDHs who underwent urgent surgery or before and after 5 days of discontinuation of low-dose ASA.
-
METHODS: A retrospective 3-center study included patients treated for CSDH taking low-dose ASA. Aspirin was discontinued on hospital admission. Based on the timing of discontinuation, we classified patients in 3 groups: urgent (surgery at admission), surgery within 5 days, and surgery 5 days after discontinuation. Surgery consisted of minicraniotomy or burr holes. Variables analyzed were age, comorbidities, modified Rankin Scale, complications, rebleedings, and mortality. Outcome measures were acute rebleeding requiring surgery, recurrence, mortality, complications, and clinical conditions. The c2 test and the Fisher exact test were used to compare variables. Logistic regression analysis was used for defining the impact on outcome measures.
-
RESULTS: We enrolled 164 patients. After aspirin discontinuation, patients underwent surgery: on admission (69 cases
-
Key words - ASA discontinuation - Chronic subdural hematoma - Clinical outcome - CSDH - Low-dose ASA - Rebleeding
[42.1%]), within 5 days (59 patients [36%]), and after 5 days (36 cases [22%]). No correlation was observed between time of discontinuation and outcome measures, including having a worse clinical outcome. CONCLUSIONS: Our data showed that the time of discontinuation of ASA does not influence outcome.
-
INTRODUCTION
A
nticoagulant and antiplatelets therapies increase the risk for both occurrence and recurrence of chronic subdural hematomas (CSDHs)1-6 These drugs are generally used for first and secondary prevention of thrombotic-embolic events, especially in elderly people. Guidelines recommend 5e7 days of acetylsalicylic acid (ASA) suspension to perform a safer surgery.7,8 Indeed, often the neurologic deterioration of the patients does not allow to wait the recommended time for surgery. Even if the antiplatelet effect would be rationally associated with an increased morbidity and mortality in patients with a CSDH, this is not uniquely demonstrated in literature. Only few studies assessed the risks of antiplatelets in the surgical management of CSDHs3,5,9,10 Does low-dose ASA and time of its discontinuation before surgery significantly influence the patients’ outcome? The aim of this study is to compare the clinical outcome, complications, and mortality of patients suffering from CSDHs who underwent surgery before and after 5 days of discontinuation of low-dose ASA therapy.
From the 1Neurosurgery Division, Department of Morphology, Surgery, and Experimental Medicine, Ferrara University, Hospital S. Anna, Ferrara; 2Neurosurgical Clinic, Department of Neurosciences, University of Messina, Messina; 3Department of Neurosurgery, Chieti University G. D’Annunzio, Santo Spirito Hospital, Pescara; and 4Neurosurgery Division, “M. Bufalini” Hospital, Cesena, Italy To whom correspondence should be addressed: Alba Scerrati, M.D. [E-mail: [email protected]] Alba Scerrati, Antonino Germanò, and Gianluca Trevisi equally contributed to the article.
Abbreviations and Acronyms ASA: Acetylsalicylic acid CCI: Charlson Comorbidity Index CSDH: Chronic subdural hematoma CT: Computed tomography
Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.05.252 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
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ORIGINAL ARTICLE ALBA SCERRATI ET AL.
ASPIRIN DISCONTINUATION ON SURGERY FOR CSDH
METHODS Patients This is a retrospective 3-center study including patients under chronic therapy with low-dose ASA (75 mg or 100 mg orally, once a day) treated for CSDH at the Neurosurgery Department of S. Anna University Hospital, Ferrara (July 2012 through October 2016), at the Neurotrauma Department of Catholic University School of Medicine, Rome (January 2010 through October 2016), and at the Neurosurgery Department of University of Messina (January 2012 through October 2016). An electronic database search with International Classification of Diseases, Ninth Revision codes 432.1 for the diagnosis and 01.24, 01.25, 01.31 for the treatment was performed in the 3 centers involved. Clinical information including drugs used and patient clinical conditions on admission and during hospital stay were obtained through analysis of patients’ medical records. Only patients under chronic therapy with single therapy lowdose aspirin were selected for this study. We double-checked with the patient and the family (if present) or the nursing staff of the retirement homes that aspirin was taken up to the day of admission. Indications for surgery included 1-sided and/or bilateral symptomatic CSDH. Surgical techniques used were minicraniotomy or burr holes, hematoma irrigation, and subdural drainage under local anesthesia plus sedation (drainage was removed within 72 hours after surgery). Perioperative second generation cephalosporins were administered for surgical prophylaxis. Aspirin was discontinued on hospital admission for all patients. The surgical procedure was performed in an emergency setting for patients who showed marked sensory disturbance or rapidly progressive neurologic deterioration. Therefore, based on time between aspirin discontinuation and surgery, we identified 3 different groups of patients: urgent (surgery at patient hospital admission), surgery within 5 days, and surgery performed at least 5 days after discontinuation. Platelets transfusion was not administered because it is not clearly demonstrated on its use.11 Postoperatively, aspirin was resumed balancing the risks of rebleeding with the risks of thromboembolic complications. In patients at higher risk of thromboembolic complications, early resumption at 72 hours, after a head computed tomography (CT) scan, was done. In patients with lower risk, medications were resumed after at least 15 days. Patients underwent postoperative CT scans within 48 hours after surgery or before in case of worsening clinical conditions. Patients with persistence of hematoma after surgery or patients with acute rebleeding were reoperated. Rebleeding was defined as an evidence of a new acute/subacute considerable amount of blood on postoperative CT scans determining significant brain compression. Patients were followed-up at 1 and 6 months. All patients underwent a 1-month follow-up head CT scan. Patients with residual hematoma underwent further CT scans until its disappearance. Statistical Analysis The primary outcome measures were acute rebleeding requiring revision surgery within hospital stay, and the CSDH recurrence defined as reaccumulation of the hematoma within the
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postoperative hematoma cavity and the reappearance of neurologic symptoms after discharge. Secondary outcome measures were mortality (up to 1 month after surgery), complications (cardiovascular events, thromboembolic events, infections, other intracranial bleedings different than the site of CSDH, seizures), and clinical conditions. Considering that clinical conditions for most patients were determined by comorbidities and preexisting clinical status, we decided to divide clinical outcome into good (stable, improved clinical conditions) versus bad (worsening clinical conditions or died). Variables analyzed were age (cut-off 80 years), location before hospital (home vs. other structure), comorbidities (Charlson Comorbidity Index [CCI]: up to 3; 3-5; 6 or more), and modified Rankin Scale (cut-off: 3). For the purposes of this study, we also analyzed the impact of timing of aspirin discontinuation before surgery on outcome measures (urgent-surgery at patient hospital admission; surgery within 5 days, and surgery performed at least 5 days after admission). The statistical analyses were carried out using the IBM SPSS Statistics Version 23 for Mac (IBM Corporation, Armonk, New York, USA). The c2 test and the Fisher exact test were used to compare variables. Logistic regression analysis was used for defining the impact of variables on outcome measures: complications (yes vs. no), mortality, rebleeding (yes vs. no), CSDH recurrence, and clinical outcome (good vs. bad, as defined previously). Results presenting P 0.05 were considered statistically significant. RESULTS We enrolled 164 patients. The mean age was 79 years. Baseline patients’ characteristics are reported in Table 1. After discontinuation of aspirin, 69 (42.0%) patients underwent urgent surgery, 59 (36%) patients underwent surgery within 5 days, and 36 (22%) patients underwent surgery after 5 days. Twenty-one (12.8%) patients presented acute rebleeding requiring further surgical intervention for evacuation. Complications occurred in 33 patients (20.1%). Twenty patients (12.2%) had CSDH recurrence, as previously defined. At the final follow-up, 51 (31.1%) patients showed an improvement of neurologic symptoms, 80 (48.8%) patients presented with stable neurologic conditions, whereas 18 (11%) patients showed worsened neurologic status, and 15 (9.1%) patients died. The overall preoperative comorbidities were assessed using CCI: 28 (17%) patients showed a good CCI (up to 3), 28 (17%) patients showed a crippling CCI (4-5), whereas 108 (66%) patients showed a bad CCI (6 or more). The mean CCI value was 4,6. At univariate analysis, age and location before recovery were not associated with outcome variables. CCI showed a trend toward significance with respect to mortality: the higher the CCI, the higher the mortality rate (4%, 9%, 24% for patients with CCI up to 3, 4-5, and 6 or more, respectively; P ¼ 0.06). CCI also correlated with clinical outcome: a bad outcome (worsening clinical conditions or died) was observed in 8%, 18% and 43% for patients with CCI up to 3, 4-5, and 6 or more, respectively (P ¼ 0.009). The effect of timing of aspirin discontinuation only correlated with mortality at the univariate analysis: mortality was 16%, 8%, and 3% for patients who underwent urgent surgery, surgery within 5 days, and surgery performed at least 5 days after
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.05.252
ORIGINAL ARTICLE ALBA SCERRATI ET AL.
ASPIRIN DISCONTINUATION ON SURGERY FOR CSDH
Table 1. Baseline Characteristics (Percentage are Reported by Groups of Surgery) Characteristics
Total (n [ 164) (% of Total)
Urgent Group, n
Surgery within 5 Days, n
Surgery after 5 Days, n
69
59
36
53 (32.3%)
23
14
16
87 (53%)
33
37
17
110 (67.1%)
44
36
30
CCI up to 3
28 (17.1%)
13
8
7
CCI 4-5
108 (65.8%)
43
41
24
Timing of surgery Female sex Age > 80 years Location before admission (home)
CCI 6 or more
28 (17.1%)
13
10
5
Complications
33 (20.1%)
16
9
8
Acute rebleeding with surgery
21 (12.8%)
10
6
5
Recurrence
20 (12.2%)
7
7
6
Clinical conditions worsened
14 (8.5%)
4
4
6
Clinical conditions stable
80 (48.8%)
38
31
11
Clinical conditions improved
36 (22%)
9
13
14
Mortality
15 (9.1%)
10
4
1
CCI, Charlson Comorbidity Index.
admission, respectively (P ¼ 0.04). However, this result was not confirmed by the multivariate analysis. No correlation was observed between time of aspirin discontinuation and other outcome variables, including rebleeding (12%, 14%, and 13%, respectively; P ¼ 0.8), CSDH recurrence at follow-up (4.2%, 4.2%, and 3.7%, respectively; P ¼ 0.8), and clinical conditions (stable-improved patients were 77%, 84.6%, 78%, respectively; P ¼ 0.58). At multivariate analysis, none of the analyzed factors correlated with complications, rebleeding, recurrence, and mortality (Tables 2-5). Patients with a higher comorbidity rate (CCI 6 or more) had a 8.7-fold risk of having a bad clinical outcome (P ¼ 0. 018) (Table 6).
Table 2. Logistic Regression Analysis. Outcome Measure: Mortality
DISCUSSION The perioperative management of low-dose aspirin in patients undergoing surgery for CSDHs is still a frequent and challenging issue. These patients are critical and often burdened with many comorbidities. The risk of bleeding and thromboembolic complications must always be balanced carefully.3 Definitive guidelines for the perioperative management of these patients are still lacking. Timing of ASA Discontinuation and Influence on Clinical Outcome ASA effect usually vanishes almost completely after 3 days of discontinuation12,13; however, many times because of a clinical deterioration, patients need surgery before this time. Although the increased risk of occurrence and recurrence of CSDH in patients Table 3. Logistic Regression Analysis. Outcome Measure: Complications
95% CI for OR Characteristics
P
OR
Inferior
Aspirin discontinued urgent
0.114
Aspirin discontinued up to 5 days
0.144
0.389
0.110
Aspirin discontinued 5 days or more
0.084
0.153
Age (cut-off 80 years)
0.630
1.371
CCI up to 3
0.121
CCI 4-5
0.505
CCI 6 or more
0.119
Superior
95% CI for OR Characteristics
P
OR
Inferior
Superior
Aspirin discontinued urgent
0.995
1.380
Aspirin discontinued up to 5 days
0.982
0.986
0.294
3.309
0.018
1.289
Aspirin discontinued 5 days or more
0.938
1.051
0.299
3.687
0.379
4.963
Age (cut-off 80 years)
0.930
0.951
0.313
2.888
CCI up to 3
0.603
2.192
0.218
22.001
CCI 4-5
0.615
1.791
0.185
17.365
7.046
0.607
81.767
CCI 6 or more
0.975
0.961
0.076
12.072
CI, confidence interval; OR, odds ratio; CCI, Charlson Comorbidity Index.
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CI, confidence interval; OR, odds ratio; CCI, Charlson Comorbidity Index.
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Table 4. Logistic Regression Analysis. Outcome Measure: Multiple Surgeries
Table 6. Logistic Regression Analysis. Outcome Measure: Clinical Outcome
95% CI for OR Characteristics
P
OR
Inferior
Superior
95% CI for OR Characteristics Aspirin discontinued urgent
P
OR
Inferior
Superior
Aspirin discontinued urgent
0.704
Aspirin discontinued up to 5 days
0.415
0.635
0.213
1.892
Aspirin discontinued up to 5 days
0.283
0.578
0.212
1.573
Aspirin discontinued 5 days or more
0.913
0.937
0.292
3.006
Aspirin discontinued 5 days or more
0.875
0.918
0.315
2.671
Age (cut-off 80 years)
0.977
1.015
0.367
2.806
Age (cut-off 80 years)
0.849
1.096
0.425
2.830
CCI up to 3
0.549
CCI up to 3
0.021
CCI 4-5
0.318
2.334
0.442
12.308
CCI 4-5
0.250
2.646
0.505
13.869
CCI 6 or more
0.648
1.587
0.219
11.490
CCI 6 or more
0.018
8.756
1.450
52.886
CI, confidence interval; OR, odds ratio; CCI, Charlson Comorbidity Index.
Bold values indicate significant statistical P value with its relative odds ratio. CI, confidence interval; OR, odds ratio; CCI, Charlson Comorbidity Index.
taking antiplatelets and anticoagulant drugs has been widely demonstrated,5,6,14-18 few evidences occur regarding the time of discontinuation of ASA and its effect on complications and clinical outcome. Kamenova et al.3 performed a study enrolling 198 patients who were receiving low-dose ASA treatment; in 26 patients, the drug discontinuation was not possible before surgery, whereas in the remaining patients, ASA was discontinued at least for 7 days. They did not find any statistically significant difference between the 2 groups in terms of recurrence, cardiovascular event rates, surgical morbidity, and mortality. Similar findings were published by Mizutani et al.19 They compared clinical outcomes of 2 groups of patients suffering from CSDH: 52 were not taking antiplatelets, whereas 9 did not discontinue it. They found no significant differences in the recurrence or mortality rates between the 2 groups. On the contrary, Forster et al.20 found that preoperative medication with antiplatelets was associated with recurrence of the hematoma requiring reoperation: in 38 patients taking
Table 5. Logistic Regression Analysis. Outcome Measure: Chronic Subdural Hematoma Recurrence 95% CI for OR Characteristics
P
OR
Inferior
Superior
Aspirin discontinued urgent
0.713
Aspirin discontinued up to 5 days
0.434
0.647
0.217
1.927
Aspirin discontinued 5 days or more
0.615
0.727
0.210
2.520
Age (cut-off 80 years)
0.854
0.908
0.324
2.545
CCI up to 3
0.581
CCI 4-5
0.326
2.304
0.436
12.169
CCI 6 or more
0.611
1.672
0.231
12.092
CI, confidence interval; OR, odds ratio; CCI, Charlson Comorbidity Index.
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0.545
preoperative antiplatelets, 12 needed a second operation (P < 0.05). These reoperations worsened the quality of life of their patient population (P < 0.05). In our study, we did not found any significant difference in terms of rebleeding (12%, 14%, and 13%, respectively; P ¼ 0.8), CSDH recurrence at follow-up (4.2%, 4.2%, and 3.6%, respectively; P ¼ 0.8), and clinical conditions (stable-improved patients were 77%, 84.6%, 78%, respectively; P ¼ 0.58). These results are similar to the ones of Kamenova3 and Mizutani.19 The effect of timing discontinuation of ASA only correlated with mortality in the univariate analysis: the discontinuation longer than 5 days reduced the mortality (P ¼ 0.04). CCI and Influence on Clinical Outcome These data, together with the trend of CCI correlation to mortality (the higher the CCI, the higher the mortality rate), are easily understandable, given that patients with poorer clinical conditions need surgery as soon as possible. CCI, as already previously reported, seems to play a significant role in terms of outcome and mortality for patients suffering from CSDH. We still need to outline, despite the good size of our sample, that this is a retrospective study, with all limitations regarding such kind of studies (see Limitations section). Clinical Implications of our Findings Clinical implications of our study could be useful in the management of patients who are taking low-dose ASA for secondary prophylaxis when a discontinuation could be very risky for cardio-embolic events. In this particular group of patients, balancing the risk could lead to continuation of the ASA, even when undergoing surgery for CSDH. Limitations This is a retrospective multicenter study presenting the following limitations: some key statistics cannot be measured, selection bias and misclassification or information bias can be introduced. Moreover, retrospectively, the temporal relationship is frequently difficult to assess. We enrolled exclusively patients who were
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.05.252
ORIGINAL ARTICLE ALBA SCERRATI ET AL.
ASPIRIN DISCONTINUATION ON SURGERY FOR CSDH
taking ASA; patients on other kinds of anticoagulant and antithrombotic drugs were excluded. CONCLUSIONS Clear guidelines regarding the perioperative management of patients with ASA therapy are still lacking. The aim of our study was to compare the perioperative and postoperative
REFERENCES 1. Sim YW, Min KS, Lee MS, Kim YG, Kim DH. Recent changes in risk factors of chronic subdural hematoma. J Korean Neurosurg Soc. 2012;52:234-239.
complication rates of patients undergoing surgery for CSDH with different times of low-dose ASA discontinuation. This is a retrospective study and presents different limitations and a poor level of evidence. From our data emerged that the time of discontinuation could not be the most significant factor playing a role in the outcome, complications, and rebleeding.
9. Okano A, Oya S, Fujisawa N, et al. Analysis of risk factors for chronic subdural haematoma recurrence after burr hole surgery: optimal management of patients on antiplatelet therapy. Br J Neurosurg. 2014;28:204-208.
2. De Bonis P, Trevisi G, de Waure C, et al. Antiplatelet/anticoagulant agents and chronic subdural hematoma in the elderly. PLoS One. 2013;8: e68732.
10. Kamenova M, Mueller C, Coslovsky M, Guzman R, Mariani L, Soleman J. Low-dose aspirin and burr-hole drainage of chronic subdural hematoma: study protocol for a randomized controlled study. Trials. 2019;20:70.
3. Kamenova M, Nevzati E, Lutz K, et al. Burr-hole drainage for chronic subdural hematoma under low-dose acetylsalicylic acid: a comparative risk analysis study. World Neurosurg. 2017;100:594-600.
11. Campbell PG, Sen A, Yadla S, Jabbour P, Jallo J. Emergency reversal of antiplatelet agents in patients presenting with an intracranial hemorrhage: a clinical review. World Neurosurg. 2010;74:279-285.
4. Guha D, Coyne S, Macdonald RL. Timing of the resumption of antithrombotic agents following surgical evacuation of chronic subdural hematomas: a retrospective cohort study. J Neurosurg. 2016;124:750-759.
12. Mantz J, Samama CM, Tubach F, et al. Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial. Br J Anaesth. 2011;107:899-910.
5. Poon MTC, Rea C, Kolias AG, Brennan PM. British Neurosurgical Trainee Research Collaborative (BNTRC). Influence of antiplatelet and anticoagulant drug use on outcomes after chronic subdural hematoma drainage [e-pub ahead of print]. J Neurotrauma. 2019. https://doi.org/ 10.1089/neu.2018.6080, accessed May 15, 2019. 6. Scerrati A, Mangiola A, Rigoni F, et al. Do antiplatelet and anticoagulant drugs modify outcome of patients treated for chronic subdural hematoma? Still a controversial issue [e-pub ahead of print]. J Neurosurg Sci. 2019. https://doi.org/ 10.23736/S0390-5616.18.04311-4, accessed May 15, 2019. 7. Mehta V, Harward SC, Sankey EW, Nayar G, Codd PJ. Evidence based diagnosis and management of chronic subdural hematoma: a review of the literature. J Clin Neurosci. 2018;50:7-15. 8. Macdonald RL. Management of intracranial hemorrhage in the anticoagulated patient. Neurosurg Clin N Am. 2018;29:605-613.
13. Korte W, Cattaneo M, Chassot PG, et al. Perioperative management of antiplatelet therapy in patients with coronary artery disease: joint position paper by members of the working group on Perioperative Haemostasis of the Society on Thrombosis and Haemostasis Research (GTH), the working group on Perioperative Coagulation of the Austrian Society for Anesthesiology, Resuscitation and Intensive Care (OGARI) and the Working Group Thrombosis of the European Society for Cardiology (ESC). Thromb Haemost. 2011; 105:743-749. 14. Baechli H, Nordmann A, Bucher HC, Gratzl O. Demographics and prevalent risk factors of chronic subdural haematoma: results of a large single-center cohort study. Neurosurg Rev. 2004;27: 263-266.
16. Dobran M, Iacoangeli M, Scortichini AR, et al. Spontaneous chronic subdural hematoma in young adult: the role of missing coagulation facto. G Chir. 2017;38:66-70. 17. Motoie R, Karashima S, Otsuji R, et al. Recurrence in 787 patients with chronic subdural hematoma: retrospective cohort investigation of associated factors including direct oral anticoagulant use. World Neurosurg. 2018;118:e87-e91. 18. Nathan S, Goodarzi Z, Jette N, Gallagher C, Holroyd-Leduc J. Anticoagulant and antiplatelet use in seniors with chronic subdural hematoma: systematic review. Neurology. 2017;88:1889-1893. 19. Mizutani K, Miwa T, Tamura R, Tomita H. The perioperative management of antiplatelet agents for chronic subdural hematoma. Clin Neurol Neurosurg. 2014;117:100-101. 20. Forster MT, Mathe AK, Senft C, Scharrer I, Seifert V, Gerlach R. The influence of preoperative anticoagulation on outcome and quality of life after surgical treatment of chronic subdural hematoma. J Clin Neurosci. 2010;17:975-979.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 19 April 2019; accepted 30 May 2019 Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.05.252 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com
15. Wang H, Zhang M, Zheng H, et al. The effects of antithrombotic drugs on the recurrence and mortality in patients with chronic subdural hematoma: a meta-analysis. Medicine (Baltimore). 2019;98:e13972.
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Timing of Low-Dose Aspirin Discontinuation and the Influence on Clinical Outcome of Patients Undergoing Surgery for Chronic Subdural Hematoma Alba Scerrati1, Antonino Germano`2, Gianluca Trevisi3, Jacopo Visani1, Giorgio Lofrese4, Luca D’Angelo1, Giovanni Raffa2, Elena Fazzari2, Annunziato Mangiola3, Michele Alessandro Cavallo1, Pasquale De Bonis1
BACKGROUND: An appropriate time (5e7 days) of discontinuation of low-dose acetylsalicylic acid (ASA) in patients undergoing surgery for chronic subdural hematoma (CSDH) is recommended. However, patient clinical deterioration often does not allow to wait the recommended time for surgery. Clear guidelines regarding the perioperative management of patients with ASA therapy are still lacking. The aim of this study is to compare the surgical outcome, complications, and mortality of patients suffering from CSDHs who underwent urgent surgery or before and after 5 days of discontinuation of low-dose ASA.
-
METHODS: A retrospective 3-center study included patients treated for CSDH taking low-dose ASA. Aspirin was discontinued on hospital admission. Based on the timing of discontinuation, we classified patients in 3 groups: urgent (surgery at admission), surgery within 5 days, and surgery 5 days after discontinuation. Surgery consisted of minicraniotomy or burr holes. Variables analyzed were age, comorbidities, modified Rankin Scale, complications, rebleedings, and mortality. Outcome measures were acute rebleeding requiring surgery, recurrence, mortality, complications, and clinical conditions. The c2 test and the Fisher exact test were used to compare variables. Logistic regression analysis was used for defining the impact on outcome measures.
-
RESULTS: We enrolled 164 patients. After aspirin discontinuation, patients underwent surgery: on admission (69 cases
-
Key words - ASA discontinuation - Chronic subdural hematoma - Clinical outcome - CSDH - Low-dose ASA - Rebleeding
[42.1%]), within 5 days (59 patients [36%]), and after 5 days (36 cases [22%]). No correlation was observed between time of discontinuation and outcome measures, including having a worse clinical outcome. CONCLUSIONS: Our data showed that the time of discontinuation of ASA does not influence outcome.
-
INTRODUCTION
A
nticoagulant and antiplatelets therapies increase the risk for both occurrence and recurrence of chronic subdural hematomas (CSDHs)1-6 These drugs are generally used for first and secondary prevention of thrombotic-embolic events, especially in elderly people. Guidelines recommend 5e7 days of acetylsalicylic acid (ASA) suspension to perform a safer surgery.7,8 Indeed, often the neurologic deterioration of the patients does not allow to wait the recommended time for surgery. Even if the antiplatelet effect would be rationally associated with an increased morbidity and mortality in patients with a CSDH, this is not uniquely demonstrated in literature. Only few studies assessed the risks of antiplatelets in the surgical management of CSDHs3,5,9,10 Does low-dose ASA and time of its discontinuation before surgery significantly influence the patients’ outcome? The aim of this study is to compare the clinical outcome, complications, and mortality of patients suffering from CSDHs who underwent surgery before and after 5 days of discontinuation of low-dose ASA therapy.
From the 1Neurosurgery Division, Department of Morphology, Surgery, and Experimental Medicine, Ferrara University, Hospital S. Anna, Ferrara; 2Neurosurgical Clinic, Department of Neurosciences, University of Messina, Messina; 3Department of Neurosurgery, Chieti University G. D’Annunzio, Santo Spirito Hospital, Pescara; and 4Neurosurgery Division, “M. Bufalini” Hospital, Cesena, Italy To whom correspondence should be addressed: Alba Scerrati, M.D. [E-mail: [email protected]] Alba Scerrati, Antonino Germanò, and Gianluca Trevisi equally contributed to the article.
Abbreviations and Acronyms ASA: Acetylsalicylic acid CCI: Charlson Comorbidity Index CSDH: Chronic subdural hematoma CT: Computed tomography
Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.05.252 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
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ORIGINAL ARTICLE ALBA SCERRATI ET AL.
ASPIRIN DISCONTINUATION ON SURGERY FOR CSDH
METHODS Patients This is a retrospective 3-center study including patients under chronic therapy with low-dose ASA (75 mg or 100 mg orally, once a day) treated for CSDH at the Neurosurgery Department of S. Anna University Hospital, Ferrara (July 2012 through October 2016), at the Neurotrauma Department of Catholic University School of Medicine, Rome (January 2010 through October 2016), and at the Neurosurgery Department of University of Messina (January 2012 through October 2016). An electronic database search with International Classification of Diseases, Ninth Revision codes 432.1 for the diagnosis and 01.24, 01.25, 01.31 for the treatment was performed in the 3 centers involved. Clinical information including drugs used and patient clinical conditions on admission and during hospital stay were obtained through analysis of patients’ medical records. Only patients under chronic therapy with single therapy lowdose aspirin were selected for this study. We double-checked with the patient and the family (if present) or the nursing staff of the retirement homes that aspirin was taken up to the day of admission. Indications for surgery included 1-sided and/or bilateral symptomatic CSDH. Surgical techniques used were minicraniotomy or burr holes, hematoma irrigation, and subdural drainage under local anesthesia plus sedation (drainage was removed within 72 hours after surgery). Perioperative second generation cephalosporins were administered for surgical prophylaxis. Aspirin was discontinued on hospital admission for all patients. The surgical procedure was performed in an emergency setting for patients who showed marked sensory disturbance or rapidly progressive neurologic deterioration. Therefore, based on time between aspirin discontinuation and surgery, we identified 3 different groups of patients: urgent (surgery at patient hospital admission), surgery within 5 days, and surgery performed at least 5 days after discontinuation. Platelets transfusion was not administered because it is not clearly demonstrated on its use.11 Postoperatively, aspirin was resumed balancing the risks of rebleeding with the risks of thromboembolic complications. In patients at higher risk of thromboembolic complications, early resumption at 72 hours, after a head computed tomography (CT) scan, was done. In patients with lower risk, medications were resumed after at least 15 days. Patients underwent postoperative CT scans within 48 hours after surgery or before in case of worsening clinical conditions. Patients with persistence of hematoma after surgery or patients with acute rebleeding were reoperated. Rebleeding was defined as an evidence of a new acute/subacute considerable amount of blood on postoperative CT scans determining significant brain compression. Patients were followed-up at 1 and 6 months. All patients underwent a 1-month follow-up head CT scan. Patients with residual hematoma underwent further CT scans until its disappearance. Statistical Analysis The primary outcome measures were acute rebleeding requiring revision surgery within hospital stay, and the CSDH recurrence defined as reaccumulation of the hematoma within the
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postoperative hematoma cavity and the reappearance of neurologic symptoms after discharge. Secondary outcome measures were mortality (up to 1 month after surgery), complications (cardiovascular events, thromboembolic events, infections, other intracranial bleedings different than the site of CSDH, seizures), and clinical conditions. Considering that clinical conditions for most patients were determined by comorbidities and preexisting clinical status, we decided to divide clinical outcome into good (stable, improved clinical conditions) versus bad (worsening clinical conditions or died). Variables analyzed were age (cut-off 80 years), location before hospital (home vs. other structure), comorbidities (Charlson Comorbidity Index [CCI]: up to 3; 3-5; 6 or more), and modified Rankin Scale (cut-off: 3). For the purposes of this study, we also analyzed the impact of timing of aspirin discontinuation before surgery on outcome measures (urgent-surgery at patient hospital admission; surgery within 5 days, and surgery performed at least 5 days after admission). The statistical analyses were carried out using the IBM SPSS Statistics Version 23 for Mac (IBM Corporation, Armonk, New York, USA). The c2 test and the Fisher exact test were used to compare variables. Logistic regression analysis was used for defining the impact of variables on outcome measures: complications (yes vs. no), mortality, rebleeding (yes vs. no), CSDH recurrence, and clinical outcome (good vs. bad, as defined previously). Results presenting P 0.05 were considered statistically significant. RESULTS We enrolled 164 patients. The mean age was 79 years. Baseline patients’ characteristics are reported in Table 1. After discontinuation of aspirin, 69 (42.0%) patients underwent urgent surgery, 59 (36%) patients underwent surgery within 5 days, and 36 (22%) patients underwent surgery after 5 days. Twenty-one (12.8%) patients presented acute rebleeding requiring further surgical intervention for evacuation. Complications occurred in 33 patients (20.1%). Twenty patients (12.2%) had CSDH recurrence, as previously defined. At the final follow-up, 51 (31.1%) patients showed an improvement of neurologic symptoms, 80 (48.8%) patients presented with stable neurologic conditions, whereas 18 (11%) patients showed worsened neurologic status, and 15 (9.1%) patients died. The overall preoperative comorbidities were assessed using CCI: 28 (17%) patients showed a good CCI (up to 3), 28 (17%) patients showed a crippling CCI (4-5), whereas 108 (66%) patients showed a bad CCI (6 or more). The mean CCI value was 4,6. At univariate analysis, age and location before recovery were not associated with outcome variables. CCI showed a trend toward significance with respect to mortality: the higher the CCI, the higher the mortality rate (4%, 9%, 24% for patients with CCI up to 3, 4-5, and 6 or more, respectively; P ¼ 0.06). CCI also correlated with clinical outcome: a bad outcome (worsening clinical conditions or died) was observed in 8%, 18% and 43% for patients with CCI up to 3, 4-5, and 6 or more, respectively (P ¼ 0.009). The effect of timing of aspirin discontinuation only correlated with mortality at the univariate analysis: mortality was 16%, 8%, and 3% for patients who underwent urgent surgery, surgery within 5 days, and surgery performed at least 5 days after
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.05.252
ORIGINAL ARTICLE ALBA SCERRATI ET AL.
ASPIRIN DISCONTINUATION ON SURGERY FOR CSDH
Table 1. Baseline Characteristics (Percentage are Reported by Groups of Surgery) Characteristics
Total (n [ 164) (% of Total)
Urgent Group, n
Surgery within 5 Days, n
Surgery after 5 Days, n
69
59
36
53 (32.3%)
23
14
16
87 (53%)
33
37
17
110 (67.1%)
44
36
30
CCI up to 3
28 (17.1%)
13
8
7
CCI 4-5
108 (65.8%)
43
41
24
Timing of surgery Female sex Age > 80 years Location before admission (home)
CCI 6 or more
28 (17.1%)
13
10
5
Complications
33 (20.1%)
16
9
8
Acute rebleeding with surgery
21 (12.8%)
10
6
5
Recurrence
20 (12.2%)
7
7
6
Clinical conditions worsened
14 (8.5%)
4
4
6
Clinical conditions stable
80 (48.8%)
38
31
11
Clinical conditions improved
36 (22%)
9
13
14
Mortality
15 (9.1%)
10
4
1
CCI, Charlson Comorbidity Index.
admission, respectively (P ¼ 0.04). However, this result was not confirmed by the multivariate analysis. No correlation was observed between time of aspirin discontinuation and other outcome variables, including rebleeding (12%, 14%, and 13%, respectively; P ¼ 0.8), CSDH recurrence at follow-up (4.2%, 4.2%, and 3.7%, respectively; P ¼ 0.8), and clinical conditions (stable-improved patients were 77%, 84.6%, 78%, respectively; P ¼ 0.58). At multivariate analysis, none of the analyzed factors correlated with complications, rebleeding, recurrence, and mortality (Tables 2-5). Patients with a higher comorbidity rate (CCI 6 or more) had a 8.7-fold risk of having a bad clinical outcome (P ¼ 0. 018) (Table 6).
Table 2. Logistic Regression Analysis. Outcome Measure: Mortality
DISCUSSION The perioperative management of low-dose aspirin in patients undergoing surgery for CSDHs is still a frequent and challenging issue. These patients are critical and often burdened with many comorbidities. The risk of bleeding and thromboembolic complications must always be balanced carefully.3 Definitive guidelines for the perioperative management of these patients are still lacking. Timing of ASA Discontinuation and Influence on Clinical Outcome ASA effect usually vanishes almost completely after 3 days of discontinuation12,13; however, many times because of a clinical deterioration, patients need surgery before this time. Although the increased risk of occurrence and recurrence of CSDH in patients Table 3. Logistic Regression Analysis. Outcome Measure: Complications
95% CI for OR Characteristics
P
OR
Inferior
Aspirin discontinued urgent
0.114
Aspirin discontinued up to 5 days
0.144
0.389
0.110
Aspirin discontinued 5 days or more
0.084
0.153
Age (cut-off 80 years)
0.630
1.371
CCI up to 3
0.121
CCI 4-5
0.505
CCI 6 or more
0.119
Superior
95% CI for OR Characteristics
P
OR
Inferior
Superior
Aspirin discontinued urgent
0.995
1.380
Aspirin discontinued up to 5 days
0.982
0.986
0.294
3.309
0.018
1.289
Aspirin discontinued 5 days or more
0.938
1.051
0.299
3.687
0.379
4.963
Age (cut-off 80 years)
0.930
0.951
0.313
2.888
CCI up to 3
0.603
2.192
0.218
22.001
CCI 4-5
0.615
1.791
0.185
17.365
7.046
0.607
81.767
CCI 6 or more
0.975
0.961
0.076
12.072
CI, confidence interval; OR, odds ratio; CCI, Charlson Comorbidity Index.
WORLD NEUROSURGERY -: e1-e5, - 2019
CI, confidence interval; OR, odds ratio; CCI, Charlson Comorbidity Index.
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ORIGINAL ARTICLE ALBA SCERRATI ET AL.
ASPIRIN DISCONTINUATION ON SURGERY FOR CSDH
Table 4. Logistic Regression Analysis. Outcome Measure: Multiple Surgeries
Table 6. Logistic Regression Analysis. Outcome Measure: Clinical Outcome
95% CI for OR Characteristics
P
OR
Inferior
Superior
95% CI for OR Characteristics Aspirin discontinued urgent
P
OR
Inferior
Superior
Aspirin discontinued urgent
0.704
Aspirin discontinued up to 5 days
0.415
0.635
0.213
1.892
Aspirin discontinued up to 5 days
0.283
0.578
0.212
1.573
Aspirin discontinued 5 days or more
0.913
0.937
0.292
3.006
Aspirin discontinued 5 days or more
0.875
0.918
0.315
2.671
Age (cut-off 80 years)
0.977
1.015
0.367
2.806
Age (cut-off 80 years)
0.849
1.096
0.425
2.830
CCI up to 3
0.549
CCI up to 3
0.021
CCI 4-5
0.318
2.334
0.442
12.308
CCI 4-5
0.250
2.646
0.505
13.869
CCI 6 or more
0.648
1.587
0.219
11.490
CCI 6 or more
0.018
8.756
1.450
52.886
CI, confidence interval; OR, odds ratio; CCI, Charlson Comorbidity Index.
Bold values indicate significant statistical P value with its relative odds ratio. CI, confidence interval; OR, odds ratio; CCI, Charlson Comorbidity Index.
taking antiplatelets and anticoagulant drugs has been widely demonstrated,5,6,14-18 few evidences occur regarding the time of discontinuation of ASA and its effect on complications and clinical outcome. Kamenova et al.3 performed a study enrolling 198 patients who were receiving low-dose ASA treatment; in 26 patients, the drug discontinuation was not possible before surgery, whereas in the remaining patients, ASA was discontinued at least for 7 days. They did not find any statistically significant difference between the 2 groups in terms of recurrence, cardiovascular event rates, surgical morbidity, and mortality. Similar findings were published by Mizutani et al.19 They compared clinical outcomes of 2 groups of patients suffering from CSDH: 52 were not taking antiplatelets, whereas 9 did not discontinue it. They found no significant differences in the recurrence or mortality rates between the 2 groups. On the contrary, Forster et al.20 found that preoperative medication with antiplatelets was associated with recurrence of the hematoma requiring reoperation: in 38 patients taking
Table 5. Logistic Regression Analysis. Outcome Measure: Chronic Subdural Hematoma Recurrence 95% CI for OR Characteristics
P
OR
Inferior
Superior
Aspirin discontinued urgent
0.713
Aspirin discontinued up to 5 days
0.434
0.647
0.217
1.927
Aspirin discontinued 5 days or more
0.615
0.727
0.210
2.520
Age (cut-off 80 years)
0.854
0.908
0.324
2.545
CCI up to 3
0.581
CCI 4-5
0.326
2.304
0.436
12.169
CCI 6 or more
0.611
1.672
0.231
12.092
CI, confidence interval; OR, odds ratio; CCI, Charlson Comorbidity Index.
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0.545
preoperative antiplatelets, 12 needed a second operation (P < 0.05). These reoperations worsened the quality of life of their patient population (P < 0.05). In our study, we did not found any significant difference in terms of rebleeding (12%, 14%, and 13%, respectively; P ¼ 0.8), CSDH recurrence at follow-up (4.2%, 4.2%, and 3.6%, respectively; P ¼ 0.8), and clinical conditions (stable-improved patients were 77%, 84.6%, 78%, respectively; P ¼ 0.58). These results are similar to the ones of Kamenova3 and Mizutani.19 The effect of timing discontinuation of ASA only correlated with mortality in the univariate analysis: the discontinuation longer than 5 days reduced the mortality (P ¼ 0.04). CCI and Influence on Clinical Outcome These data, together with the trend of CCI correlation to mortality (the higher the CCI, the higher the mortality rate), are easily understandable, given that patients with poorer clinical conditions need surgery as soon as possible. CCI, as already previously reported, seems to play a significant role in terms of outcome and mortality for patients suffering from CSDH. We still need to outline, despite the good size of our sample, that this is a retrospective study, with all limitations regarding such kind of studies (see Limitations section). Clinical Implications of our Findings Clinical implications of our study could be useful in the management of patients who are taking low-dose ASA for secondary prophylaxis when a discontinuation could be very risky for cardio-embolic events. In this particular group of patients, balancing the risk could lead to continuation of the ASA, even when undergoing surgery for CSDH. Limitations This is a retrospective multicenter study presenting the following limitations: some key statistics cannot be measured, selection bias and misclassification or information bias can be introduced. Moreover, retrospectively, the temporal relationship is frequently difficult to assess. We enrolled exclusively patients who were
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.05.252
ORIGINAL ARTICLE ALBA SCERRATI ET AL.
ASPIRIN DISCONTINUATION ON SURGERY FOR CSDH
taking ASA; patients on other kinds of anticoagulant and antithrombotic drugs were excluded. CONCLUSIONS Clear guidelines regarding the perioperative management of patients with ASA therapy are still lacking. The aim of our study was to compare the perioperative and postoperative
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 19 April 2019; accepted 30 May 2019 Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.05.252 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com
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