- Email: [email protected]
Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma
NEUCIR-303; No. of Pages 7
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
NEUROCIRUGÍA www.elsevier.es/neurocirugia
Clinical Research
Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma Tammam Abboud a,b,∗,1 , Lasse Dührsen b,1 , Christina Gibbert b,c , Manfred Westphal b , Tobias Martens b a b c
University Medical Center Göttingen, Department of Neurosurgery, Germany University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Germany Medical Center Eilbek, Department of Spine Surgery, Germany
a r t i c l e
i n f o
a b s t r a c t
Article history:
Introduction: Chronic subdural hematoma (cSDH) is a common pathology encountered in
Received 20 June 2017
neurosurgical practice, especially in elderly patients, who frequently require antithrombotic
Accepted 12 September 2017
agents. The aim of this study was to investigate the influence of antithrombotic agents on
Available online xxx
recurrence rates and clinical outcomes in patients operated for cSDH.
Keywords:
analyzed retrospectively. Presenting symptoms, coagulation testing, history of antithrom-
Chronic subdural hematoma
botic agents and comorbidities were obtained from the patient charts. The standard
Methods: A cohort of patients operated for cSDH at one center during a 5 years period was
Recurrent hematoma
neurosurgical procedure was a single burr hole under local anesthesia with insertion of
Antiplatelet drug
a subdural drainage. Questionnaires and telephone interviews were used to assess the clin-
Anticoagulant drug
ical outcome using the modified Rankin Scale (mRS). Good outcome was defined as mRS 0
Phenprocoumon
to 3 and poor outcome as mRS 4 to 6. Results: 201 patients with cSDH underwent initial surgical treatment and were enrolled in the study. The median follow-up was 81 weeks. 41 patients (20.4%) were on antiplatelet drug and 43 (21.4%) were on phenprocoumon. A recurrent hematoma required surgery in 37 patients (18.4%). A poor outcome was seen in 36 patients (17.9%). Each of older age and administration of phenprocoumon at admission was an independent risk factor predictive of poor outcome, (p = 0.001 and p = 0.031, respectively)) Administration of antithrombotic agents had no impact on hematoma recurrence. Conclusion: Administration of phenprocoumon and older age might increase the risk of poor outcome in patients with cSDH. Neither the administration of phenprocoumon nor antiplatelet drug influenced the recurrence rate of subdural hematoma in our patient cohort. ˜ ˜ S.L.U. All rights © 2017 Sociedad Espanola de Neurocirug´ıa. Published by Elsevier Espana, reserved.
∗
Corresponding author. E-mail address: [email protected] (T. Abboud). 1 Tammam Abboud and Lasse Dührsen contributed equally to this work. https://doi.org/10.1016/j.neucir.2017.09.006 ˜ ˜ S.L.U. All rights reserved. 1130-1473/© 2017 Sociedad Espanola de Neurocirug´ıa. Published by Elsevier Espana,
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
NEUCIR-303; No. of Pages 7
2
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
Influencia de los agentes anti-trombóticos en la tasa de recidiva y el resultado clínico en los pacientes operados de hematoma subdural crónico r e s u m e n Palabras clave:
Introducción: El hematoma subdural crónico (HSC) es una enfermedad común en la práctica
Hematoma subdural crónico
neuro-quirúgica, especialmente en pacientes mayores, quienes requieren con frecuen-
Hematoma recurrente
cia agentes anti-trombóticos. El objetivo de este estudio fue investigar la influencia de
Fármacos anti-plaquetarios
los agentes anti-trombóticos en las tasas de recidiva y los resultados clínicos en los pacientes
Fármacos anti-coagulantes
operados de HSC.
Fenprocumón
Métodos: Se analizó retrospectivamente una cohorte de pacientes operados de HSC en ˜ un único centro, durante un periodo de 5 anos. Se obtuvieron de las historias de los pacientes los síntomas de presentación, las pruebas de coagulación, el historial de agentes anti-trombóticos y las comorbilidades. El procedimiento quirúrgico estándar consistió en una trepanación bajo anestesia local, con inserción de un drenaje subdural. Se utilizaron cuestionarios y entrevistas telefónicas para valorar el resultado clínico mediante la Escala de Rankin modificada (mRS). El resultado favorable se definió como el valor de 0 a 3 de mRS, y el resultado desfavorable el valor de 4 a 6. Resultados: Doscientos uno pacientes con HSC fueron sometidos a tratamiento quirúrgico inicial, y fueron incluidos en el estudio. El seguimiento medio fue de 81 semanas. A 41 pacientes (20,4%) se les administró tratamiento anti-plaquetario y a 43 (21,4%) fenprocumón. El hematoma recurrente requirió cirugía en 37 pacientes (18,4%). Se observaron resultados desfavorables en 36 pacientes (17,9%). La avanzada edad y la administración de fenprocumón al ingreso resultaron factores predictivos independientes del resultado desfavorable (p = 0,001 y p = 0,031, respectivamente). La administración de agentes antitrombóticos no tuvo impacto sobre la recidiva del hematoma. Conclusión: La administración de fenprocumón y la edad avanzada pueden incrementar el riesgo de resultado desfavorable en los pacientes con HSC. Ni la administración de fenprocumón ni la de fármacos anti-plaquetarios influyeron en la tasa de hematomas subdurales en nuestra cohorte de pacientes. ˜ ˜ S.L.U. Todos de Neurocirug´ıa. Publicado por Elsevier Espana, © 2017 Sociedad Espanola los derechos reservados.
Introduction The evacuation of chronic subdural hematoma (cSDH) is one of the most common procedures in neurosurgical practice. The procedure is expected to continue to increase in frequency, since cSDH usually occurs in elderly patients and the demographic development in society leads to a rising number of patients over the age of seventy.1 Many of these patients have several comorbidities and are more likely than younger patients to be on antithrombotic drugs at admission, which makes the perioperative management including anesthesia and reversal of antithrombotic drugs more challenging. The pathophysiology behind this disease is wellunderstood and there is consensus that the process of the growing hematoma by continuous reabsorption and re-hemorrhage from the circumjacent membrane has to be disrupted. Local anesthesia and minimal invasive approaches are invaluable, in particular for multimorbid patients. However, the ideal surgical technique remains controversial. Mini-craniotomies as well as single or double burr holes are widely used.2 It is also unclear to what extent intracranial membranes must be resected.3 Further, the benefit of the
insertion of a subdural drainage appears to be unanimous though it remains debatable how long the drainage should be left in situ.4 Although the evacuation of cSDH is considered an easy and safe procedure, recurrence rates up to 33% are reported.5,6 Recurrence is often associated with a longer hospital stay and an unfavorable disease course in the elderly and sometimes multimorbid patients. Several series have analyzed the link between the intake of antithrombotic drugs and hematoma recurrence rates and have reported inconsistent results.7,8 Although there are studies that have evaluated the impact of antithrombotic agents on patients suffering from traumatic brain injury,9,10 few studies have addressed the influence of these medications on the clinical outcome of patients with cSDH. In addition, venous thromboembolism prophylaxis in patients with traumatic brain injury has been addressed in previous studies,11,12 however it has not been discussed in the context of cSDH. In this retrospective series, we introduce the surgical management of cSDH at a single center and investigate the impact of administration of antithrombotic drugs on the clinical outcome of patients surgically treated for cSDH.
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
NEUCIR-303; No. of Pages 7
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
Materials and methods All patients who presented to our department with cSDH proven by CT scan, between June 2008 and June 2013, were identified. Past medical history and neurological function were evaluated and laboratory blood tests were performed at admission. Symptomatic cSDH were assigned to surgical treatment and non-symptomatic cSDH were assigned to conservative treatment. An elevated international normalized ratio (INR) over 1.2 at admission was corrected using vitamin K and prothrombin complex concentrate, while thrombocytopenia was corrected if there was a decrease in platelet count below 50,000 per microliter. Administration of vitamin K in patients of with INR elevation was continued for three days after the procedure. Postoperative blood tests were carried out to monitor INR levels and platelet counts. Patients on antiplatelet medication underwent surgery 5 days after discontinuation of the antiplatelet, unless they were suffering from impaired consciousness, in which case an emergency procedure was performed. Patients who were on phenprocoumon for atrial fibrillation, history of thrombotic embolism in six months prior to admission or for valvular heart disease received a weight adjusted dose of low molecular weight heparin (Enoxaparin sodium; kg*ml/day). Phenprocoumon is a vitamin K antagonist and belongs to the 4-hydroxycoumarins. In some countries as USA and Spain, warfarin, which is another coumarin, is used instead as a vitamin K antagonist. For the prevention of venous thromboembolism, all patients received Enoxaparin sodium 40 mg/day (20 mg/day in case of renal insufficiency) as soon as INR levels were below 1.5. Only patients who were initially treated surgically were included in this study. The data was evaluated retrospectively according to the local ethical standards.
Surgical management and follow-up Surgical treatment was performed under local anesthesia. A minority of incompliant patients or those who were not expected to communicate properly during the procedure received general anesthesia. The supine position without pin fixation was used for all patients. After skin incision, a single burr hole was drilled over the maximum width of the hematoma. After coagulation and incision of the dura matter, the hematoma was washed out with warm irrigation using a Nelaton catheter which was inserted in all directions, if possible. In addition, any visible membranes within the cavity of the hematoma were removed. Before closure, a subdural drain (Jackson-Pratt drain) was left in place whenever possible and then removed after 48 hours. Bed rest in a supine position was recommended for all patients during the first 48 hours postoperatively. CT scans were performed after 48 hours, at 4 weeks, and at 3 and 6 months postoperatively. Recurrent hematomas were treated surgically if they were symptomatic or if they increased in size on follow-up CT scans within 6 months after the procedure.
3
Clinical data Age at surgery, presenting symptoms, administration of antithrombotic agents, history of head trauma, comorbidities, and postoperative complications were assessed by chart reviews. The comorbidities evaluated included diabetes mellitus, atrial fibrillation, arterial hypertension, valvular heart disease ease, coronary heart disease, heart failure and a history of thromboembolic events. Clinical outcome was obtained by questionnaires sent to the patients or telephone interviews and was measured using the modified Rankin Scale (mRS).13 Good outcome was defined as mRS 0 to 3 and poor outcome as mRS 4 to 6.
Statistical analyses According to preoperative administration of antithrombotic agents, patients were divided into 3 subgroups, no antithrombotic agents, antiplatelet drug and phenprocoumon. Comparison between these subgroups regarding age, comorbidities and recurrence rates was performed using Kruskal–Wallis One Way Test and Fisher Exact Test. Logistic regression was used to identify potential prognosticating factors associated with poor outcome. For all tests, a p-value less than 0.05 was considered significant. Statistical analysis and graphics were performed using IBM SPSS Statistics (v20, IBM Corp, Armonk, New York, USA), Microsoft Excel (2013, Microsoft Inc, Seattle, Washington, USA) and SigmaPlot (v12.5, Systat Software Inc, Erkrath, Germany).
Results 249 patients were treated for cSDH at one center during the study period (2008–2013). 201 patients were initially assigned for surgical treatment, were available for follow-up and could be included in this study. 48 patients were excluded from the study, either because they were initially treated conservatively or because they refused surgical treatment. 18 patients died after the procedure within a mean interval of 41 weeks (range 2 to 161 weeks). 5 patients died within 3 weeks after surgery due to postoperative complications including pneumonia, status epilepticus and recurrent bleeding. One patient with a recurrent hemorrhage died 11 weeks after surgery. All other deaths occurred beyond the last CT scan which was performed 6 months after surgery and the leading cause to death was indeterminate. The mean followup period in the remaining patients was 81 weeks (range 14 to 242 weeks). The mean age of the 201 patients (61 female and 140 male) was 72 years (range 25 to 95 years) at the time of operation. A history of fall or head trauma was reported in 85 (42.3%) cases with a mean interval of 6 weeks (range 0.5 to 21 weeks). Initial symptoms are presented in Fig. 1.
Antithrombotic agents and coagulation testing Administration of antithrombotic agents was reported in 84 (41.8%) patients upon admission: 38 patients were on aspirin, 3 on clopidogrel, 38 on phenprocoumon, 4 on aspirin plus
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
ARTICLE IN PRESS
NEUCIR-303; No. of Pages 7
4
n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
Seizures Balance disturbances Vertigo
6
5 5
5 15
4
Speech disorders
24
Impaired consciousness Headache
mRS
37 58
Limb weakness Number of patients 0
3 2
98
20
40
60
80
100
120
1 0
Fig. 1 – Presenting symptoms.
phenprocoumon, and 1 on clopidogrel plus phenprocoumon. In laboratory studies, 47 patients showed elevated INR values and 6 patients showed thrombocytopenia, which were corrected accordingly prior to the surgical procedure. No further correction of platelet count was necessary postoperatively. Because of impaired consciousness in 4 patients who were on antiplatelet medication, the procedure was performed immediately without the usual 5-day interval. Patient characteristics and comorbidities according to the administration of antithrombotic agents are summarized in Table 1. Postoperatively, unless there was proof of recurrent hematoma, administration of antiplatelet medication was continued after 2 weeks interval and administration of phenoprocoumon was continued after 4 weeks interval.
Surgical procedure and clinical outcome In 190 (94.5%) cases, surgery was performed under local anesthesia and in 11 cases (5.5%) it was performed under general anesthesia. 183 (91%) patients had an unilateral hematoma and underwent therefore a single burr hole, while 18 patients (9%) had bilateral hematomas and required two burr holes bilaterally. The procedure-related morbidity was estimated at 4.5% and mortality at 0.5%. 38 patients (18.9%) developed a recurrent hematoma after a mean of 25 days (range 1 to 126 days), one patient underwent a conservative management and 37 patients (18.4%) underwent a second procedure to evacuate the recurrent hematoma, Table 1. The second procedure was performed through the
< 70 years N=142
Patient age
=> 70 years N=59
Fig. 2 – Clinical outcome according to patient age. existing burr hole, except in two patients who received a new burr hole. 5 patients suffered a second recurrence und were consequently operated on a third time. At follow-up, good outcome was found in 165 (82.1%) patients and poor outcome was found in 36 patients (17.9%). Fig. 2 demonstrates clinical outcome using mRS according to patient age.
Comparison and statistical analysis Patient age and rate of comorbidities in the subgroup of patients with antiplatelet medication didn’t differ significantly from those in the subgroup with phenprocoumon, but were significantly higher in both subgroups than in the subgroup without antithrombotic agents (p = <0.001). No correlation between initial symptoms and patient outcome was observed (p = 0.204). None of the comorbidities had influence on clinical outcome (p = 0.067, OR 2.8, 95% CI 0.9–8.3). Recurrence of hematoma had no influence on clinical outcome (p = 0.59, OR 1.2, 95% CI 0.53–3.1). The intake of phenprocoumon was an independent predictor of poor outcome (p = 0.031, Odds ratio (OR) 2.1, 95% Confidence interval (CI) 1.0–4.3). Administration of antiplatelet drug had no measurable influence on outcome (p = 0.135, OR 1.9, 95% CI 0.8–4.7). Older patient age (> 72 years) at the time of operation was associated with a poor outcome, (p = 0.001), Table 2. Neither patient age, nor administration of antiplatelet medication or phenprocoumon had an impact on recurrent hematomas (p = 0.9, 0.7 and 0.2, respectively).
Table 1 – Patients characteristics, comorbidities and recurrence rates according to the administration of antithrombotic agents. Antithrombotic agent
Number of patients Mean age (years) Cardiovascular comorbidities Aortic valve disease Diabetes mellitus Heart failure Recurrence rate
Single antiplatelet agent
Phenprocoumon
None
41 77 29%
43 80 28%
117 70 3%
5% 17% 2% 20%
7% 16% 7% 26%
0% 10% 3% 15%
Table 2 – Predictive factors of poor outcome in patients with cSDH.
Platelet aggregation inhibitor Phenprocoumon Recurrence Comorbidities Age at operation Presenting symptoms
p-value
Odds ratio
Confidence Interval
0.135
1.9
0.8–4.7
0.031 0.536 0.067 0.001 0.204
2.4 1.3 2.8 1.1 –
1.1–5.4 0.6–3.0 0.9–8.3 1.0–1.1 –
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
NEUCIR-303; No. of Pages 7
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
Discussion Mortality and morbidity In this retrospective study, we evaluated the data of 201 patients who were operated for cSDH using a single burr hole with subdural drain. Although the mean age of 72 years in our patient cohort was similar to other studies,14–16 the estimated perioperative mortality rate of 0.5% in our series seems to be low comparing with previous studies, which have mortality rates reported between 2.75% and 13.3%.14,16–18 However, the estimated perioperative morbidity rate of 4.5% in the current series is close to the rates reported in the literature. A recurrent hematoma was found in 18.9% of our patients, which is in line with previous studies that included patient numbers similar to that of our study and reported recurrence rates between 17% and 24%.2,7,8,17,19–21 These results confirm the safety of a single burr hole under local anesthesia, as well as the use of a Nelaton catheter to evacuate the hematoma and the placement of subdural drain for treatment of cSDH.
Antiplatelet and anticoagulant agents Administration of antiplatelet or anticoagulant drugs was not a predictor of recurrent hematoma. This finding is a matter of controversy in the literature, as some studies found that the administration of anticoagulants is predictive of recurrence,8,19,22,23 while others did not find any effect of antiplatelet or anticoagulant therapy on recurrence rate.7,20,24 It is difficult to compare these studies, as they used different surgical techniques to evacuate the hematoma. Many studies have addressed the clinical outcome of patients with cSDH and the factors that were found to predict a poor outcome included older age,14,19,25 lower GCS at admission and recurrent hematoma.19 None of these series found an impact of antiplatelet or anticoagulant agents on clinical outcome. Administration of antiplatelet agents didn’t influence the outcome in the current series, while administration of phenprocoumon was an independent risk factor of poor outcome. This association has not been reported in the literature to date in the context of cSDH. Foerch et al. presented similar finding regarding intracerebral hemorrhage, as they found that in contrast to oral anticoagulants, pre-treatment with antiplatelet agents is not an independent risk factor of mortality and unfavorable outcome in patients with intracerebral hemorrhage.26 Grandhi et al. found that the pre-injury use of warfarin, but not antiplatelet agents, increased mortality in elderly traumatic brain injury patients.10 Inui et al. evaluated risk factors for mortality after presentation with a groundlevel fall among patients with and without anticoagulant agents and concluded that elderly patients on anticoagulant agents for atrial fibrillation and/or flutter who fall have a greater risk for mortality.9 Also, patients with isolated traumatic subarachnoid hemorrhage and elevated INR were found to be at higher risk of clinical deterioration.27 Trauma patients and patients undergoing neurosurgical procedures are at high risk for venous thromboembolism.12,28 Therefore, venous thromboembolism prophylaxis in patients
5
with cSDH is recommended, especially when anticoagulant agents have been withdrawn perioperatively. Although low molecular weight heparin has not been evaluated regarding its impact on cSDH, there are many studies that have evaluated its use after traumatic brain injury and found no significant risk of expanding intracranial hemorrhage.29,30 Phenprocoumon as a vitamin K antagonist causes the inhibition of synthesis of coagulation factors II, VII, IX and X. The annual rates of major bleeding in patients on vitamin K antagonists in daily care are estimated at up to 8%.31 Incidence of cSDH has been reported to be elevated in patients who are on aspirin or warfarin (another vitamin K antagonist).32 Since the administration of anticoagulant agents in most patients is linked to serious comorbidities, especially cardiac diseases. Administration of anticoagulants in this series did not correlate with a higher recurrence rate, nevertheless it was associated with a poor outcome, which might be attributed either to a rebleeding that was not detected because it happened beyond the last scheduled CT scan 6 months after surgery or due to other systemic bleeding complications that were not included in our analysis; neurosurgeons have to be aware of the impact of these medications on treatment and outcome of patients with supposedly an easily-treated pathology such as chronic subdural hematoma, and might consider a longer follow-up period in older patients and those who are on anticoagulant medication. In addition, neuro- and trauma surgeons should be aware of many new antithrombotic agents, which are increasingly implemented in daily practice, as their influence on intracranial hemorrhage is still unknown.
Limitations Our results, especially the correlation between the administration of phenprocoumon and poor outcome in patients operated for cSDH, must be interpreted carefully due to the retrospective nature of this study and the wide range of followup periods. Larger series will be necessary to confirm our findings.
Conclusions Administration of phenprocoumon in patients with cardiovascular comorbidities and older age might be predictive of poor outcome in patients with cSDH, while administration of antiplatelet drug did not seem to have an impact on clinical outcome. Neither the administration of phenprocoumon nor single platelet inhibitors influenced the recurrence of subdural hematoma in our patient cohort.
Ethical approval All procedures performed in this study were in accordance with the ethical standards of the local ethics committee and with the 1964 Helsinki declaration and its later amendments.
Conflict of interest The authors have no conflicts of interest to declare.
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
NEUCIR-303; No. of Pages 7
6
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
references
1. Kudo H, Kuwamura K, Izawa I, Sawa H, Tamaki N. Chronic subdural hematoma in elderly people: present status on Awaji Island and epidemiological prospect. Neurol Med Chir (Tokyo). 1992;32:207–9. 2. Pahatouridis D, Alexiou GA, Fotakopoulos G, Mihos E, Zigouris A, Drosos D, et al. Chronic subdural haematomas: a comparative study of an enlarged single burr hole versus double burr hole drainage. Neurosurg Rev. 2013;36:151–4, http://dx.doi.org/10.1007/s10143-012-0412-3 [discussion 154–5]. 3. Rocchi G, Caroli E, Salvati M, Delfini R. Membranectomy in organized chronic subdural hematomas: indications and technical notes. Surg Neurol. 2007;67:374–80, http://dx.doi.org/10.1016/j.surneu.2006.08.066. 4. Santarius T, Kirkpatrick PJ, Ganesan D, Chia HL, Jalloh I, Smielewski P, et al. Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial. Lancet. 2009;374:1067–73, http://dx.doi.org/10.1016/S0140-6736(09)61115-6. 5. Taussky P, Fandino J, Landolt H. Number of burr holes as independent predictor of postoperative recurrence in chronic subdural haematoma. Br J Neurosurg. 2008;22:279–82, http://dx.doi.org/10.1080/02688690701818885. 6. Wakai S, Hashimoto K, Watanabe N, Inoh S, Ochiai C, Nagai M. Efficacy of closed-system drainage in treating chronic subdural hematoma: a prospective comparative study. Neurosurgery. 1990;26:771–3. 7. Aspegren OP, Astrand R, Lundgren MI, Romner B. Anticoagulation therapy a risk factor for the development of chronic subdural hematoma. Clin Neurol Neurosurg. 2013;115:981–4, http://dx.doi.org/10.1016/j.clineuro. 2012.10.008. 8. Chon KH, Lee JM, Koh EJ, Choi HY. Independent predictors for recurrence of chronic subdural hematoma. Acta Neurochir (Wien). 2012;154:1541–8, http://dx.doi.org/10.1007/s00701-012-1399-9. 9. Inui TS, Parina R, Chang DC, Inui TS, Coimbra R. Mortality after ground-level fall in the elderly patient taking oral anticoagulation for atrial fibrillation/flutter: a long-term analysis of risk versus benefit. J Trauma Acute Care Surg. 2014;76:642–9, http://dx.doi.org/10.1097/ta.0000000000000138 [discussion 649–50]. 10. Grandhi R, Harrison G, Voronovich Z, Bauer J, Chen SH, Nicholas D, et al. Preinjury warfarin, but not antiplatelet medications, increases mortality in elderly traumatic brain injury patients. J Trauma Acute Care Surg. 2015;78:614–21, http://dx.doi.org/10.1097/ta.0000000000000542. 11. Foreman PM, Schmalz PG, Griessenauer CJ. Chemoprophylaxis for venous thromboembolism in traumatic brain injury: a review and evidence-based protocol. Clin Neurol Neurosurg. 2014;123:109–16, http://dx.doi.org/ 10.1016/j.clineuro.2014.05.017. 12. Barrera LM, Perel P, Ker K, Cirocchi R, Farinella E, Morales Uribe CH. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev. 2013;3:Cd008303, http://dx.doi.org/ 10.1002/14651858.CD008303.pub2. 13. Banks JL, Marotta CA. Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. Stroke. 2007;38:1091–6, http://dx.doi.org/10.1161/01.STR.0000258355.23810.c6. 14. Gelabert-Gonzalez M, Iglesias-Pais M, Garcia-Allut A, Martinez-Rumbo R. Chronic subdural haematoma: surgical treatment and outcome in 1000 cases. Clin Neurol Neurosurg. 2005;107:223–9, http://dx.doi.org/10.1016/j.clineuro. 2004.09.015.
15. Grobelny BT, Ducruet AF, Zacharia BE, Hickman ZL, Andersen KN, Sussman E, et al. Preoperative antiepileptic drug administration and the incidence of postoperative seizures following bur hole-treated chronic subdural hematoma. J Neurosurg. 2009;111:1257–62, http://dx.doi.org/10.3171/ 2009.6.jns0928. 16. Leroy HA, Aboukais R, Reyns N, Bourgeois P, Labreuche J, Duhamel A, et al. Predictors of functional outcomes and recurrence of chronic subdural hematomas. J Clin Neurosci. 2015, http://dx.doi.org/10.1016/j.jocn.2015.03.064. 17. Borger V, Vatter H, Oszvald A, Marquardt G, Seifert V, Guresir E. Chronic subdural haematoma in elderly patients: a retrospective analysis of 322 patients between the ages of 65-94 years. Acta Neurochir (Wien). 2012;154:1549–54, http://dx.doi.org/10.1007/s00701-012-1434-x. 18. Rohde V, Graf G, Hassler W. Complications of burr-hole craniostomy and closed-system drainage for chronic subdural hematomas: a retrospective analysis of 376 patients. Neurosurg Rev. 2002;25:89–94. 19. Amirjamshidi A, Abouzari M, Eftekhar B, Rashidi A, Rezaii J, Esfandiari K, et al. Outcomes and recurrence rates in chronic subdural haematoma. Br J Neurosurg. 2007;21:272–5, http://dx.doi.org/10.1080/02688690701272232. 20. Lindvall P, Koskinen LO. Anticoagulants and antiplatelet agents and the risk of development and recurrence of chronic subdural haematomas. J Clin Neurosci. 2009;16:1287–90, http://dx.doi.org/10.1016/j.jocn.2009.01.001. 21. Nakaguchi H, Tanishima T, Yoshimasu N. Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. J Neurosurg. 2001;95:256–62, http://dx.doi.org/10.3171/jns.2001.95.2.0256. 22. 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;88:1889–93, http://dx.doi.org/10.1212/wnl. 0000000000003918. 23. Wang Y, Zhou J, Fan C, Wang D, Jiao F, Liu B, et al. Influence of antithrombotic agents on the recurrence of chronic subdural hematomas and the quest about the recommencement of antithrombotic agents: a meta-analysis. J Clin Neurosci. 2017;38:79–83, http://dx.doi.org/10.1016/j.jocn.2016.12. 001. 24. Ohba S, Kinoshita Y, Nakagawa T, Murakami H. The risk factors for recurrence of chronic subdural hematoma. Neurosurg Rev. 2013;36:145–9, discussion 149-50, http://dx.doi.org/10.1007/s10143-012-0396-z 25. Pilitsis J, Atwater B, Warden D, Deck G, Carroll J, Smith J, et al. Outcomes in octogenarians with subdural hematomas. Clin Neurol Neurosurg. 2013;115:1429–32, http://dx.doi.org/ 10.1016/j.clineuro.2013.01.017. 26. Foerch C, Sitzer M, Steinmetz H, Neumann-Haefelin T. Pretreatment with antiplatelet agents is not independently associated with unfavorable outcome in intracerebral hemorrhage. Stroke. 2006;37:2165–7, http://dx.doi.org/ 10.1161/01.str.0000231842.32153.74. 27. von der Brelie C, Schneegans I, van den Boom L, Meier U, Hedderich J, Lemcke J. Impaired coagulation is a risk factor for clinical and radiologic deterioration in patients with traumatic brain injury and isolated traumatic subarachnoid hemorrhage. J Trauma Acute Care Surg. 2015;79:295–300, http://dx.doi.org/10.1097/ta.0000000000000722. 28. Browd SR, Ragel BT, Davis GE, Scott AM, Skalabrin EJ, Couldwell WT. Prophylaxis for deep venous thrombosis in neurosurgery: a review of the literature. Neurosurg Focus. 2004;17:E1, http://dx.doi.org/10.3171/foc.2004.17.4.1. 29. Dudley RR, Aziz I, Bonnici A, Saluja RS, Lamoureux J, Kalmovitch B, et al. Early venous thromboembolic event prophylaxis in traumatic brain injury with low-molecular-weight heparin: risks and benefits.
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
NEUCIR-303; No. of Pages 7
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
J Neurotrauma. 2010;27:2165–72, http://dx.doi.org/10.1089/ neu.2010.1366. 30. Phelan HA, Wolf SE, Norwood SH, Aldy K, Brakenridge SC, Eastman AL, et al. A randomized, double-blinded, placebo-controlled pilot trial of anticoagulation in low-risk traumatic brain injury: the Delayed Versus Early Enoxaparin Prophylaxis I (DEEP I) study. J Trauma Acute Care Surg. 2012;73:1434–41, http://dx.doi.org/10.1097/TA. 0b013e31825ac49e.
7
31. Beyer-Westendorf J, Forster K, Pannach S, Ebertz F, Gelbricht V, Thieme C, et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood. 2014;124:955–62, http://dx.doi.org/ 10.1182/blood-2014-03-563577. 32. Rust T, Kiemer N, Erasmus A. Chronic subdural haematomas and anticoagulation or anti-thrombotic therapy. J Clin Neurosci. 2006;13:823–7, http://dx.doi.org/10.1016/ j.jocn.2004.12.013.
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
NEUROCIRUGÍA www.elsevier.es/neurocirugia
Clinical Research
Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma Tammam Abboud a,b,∗,1 , Lasse Dührsen b,1 , Christina Gibbert b,c , Manfred Westphal b , Tobias Martens b a b c
University Medical Center Göttingen, Department of Neurosurgery, Germany University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Germany Medical Center Eilbek, Department of Spine Surgery, Germany
a r t i c l e
i n f o
a b s t r a c t
Article history:
Introduction: Chronic subdural hematoma (cSDH) is a common pathology encountered in
Received 20 June 2017
neurosurgical practice, especially in elderly patients, who frequently require antithrombotic
Accepted 12 September 2017
agents. The aim of this study was to investigate the influence of antithrombotic agents on
Available online xxx
recurrence rates and clinical outcomes in patients operated for cSDH.
Keywords:
analyzed retrospectively. Presenting symptoms, coagulation testing, history of antithrom-
Chronic subdural hematoma
botic agents and comorbidities were obtained from the patient charts. The standard
Methods: A cohort of patients operated for cSDH at one center during a 5 years period was
Recurrent hematoma
neurosurgical procedure was a single burr hole under local anesthesia with insertion of
Antiplatelet drug
a subdural drainage. Questionnaires and telephone interviews were used to assess the clin-
Anticoagulant drug
ical outcome using the modified Rankin Scale (mRS). Good outcome was defined as mRS 0
Phenprocoumon
to 3 and poor outcome as mRS 4 to 6. Results: 201 patients with cSDH underwent initial surgical treatment and were enrolled in the study. The median follow-up was 81 weeks. 41 patients (20.4%) were on antiplatelet drug and 43 (21.4%) were on phenprocoumon. A recurrent hematoma required surgery in 37 patients (18.4%). A poor outcome was seen in 36 patients (17.9%). Each of older age and administration of phenprocoumon at admission was an independent risk factor predictive of poor outcome, (p = 0.001 and p = 0.031, respectively)) Administration of antithrombotic agents had no impact on hematoma recurrence. Conclusion: Administration of phenprocoumon and older age might increase the risk of poor outcome in patients with cSDH. Neither the administration of phenprocoumon nor antiplatelet drug influenced the recurrence rate of subdural hematoma in our patient cohort. ˜ ˜ S.L.U. All rights © 2017 Sociedad Espanola de Neurocirug´ıa. Published by Elsevier Espana, reserved.
∗
Corresponding author. E-mail address: [email protected] (T. Abboud). 1 Tammam Abboud and Lasse Dührsen contributed equally to this work. https://doi.org/10.1016/j.neucir.2017.09.006 ˜ ˜ S.L.U. All rights reserved. 1130-1473/© 2017 Sociedad Espanola de Neurocirug´ıa. Published by Elsevier Espana,
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
NEUCIR-303; No. of Pages 7
2
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
Influencia de los agentes anti-trombóticos en la tasa de recidiva y el resultado clínico en los pacientes operados de hematoma subdural crónico r e s u m e n Palabras clave:
Introducción: El hematoma subdural crónico (HSC) es una enfermedad común en la práctica
Hematoma subdural crónico
neuro-quirúgica, especialmente en pacientes mayores, quienes requieren con frecuen-
Hematoma recurrente
cia agentes anti-trombóticos. El objetivo de este estudio fue investigar la influencia de
Fármacos anti-plaquetarios
los agentes anti-trombóticos en las tasas de recidiva y los resultados clínicos en los pacientes
Fármacos anti-coagulantes
operados de HSC.
Fenprocumón
Métodos: Se analizó retrospectivamente una cohorte de pacientes operados de HSC en ˜ un único centro, durante un periodo de 5 anos. Se obtuvieron de las historias de los pacientes los síntomas de presentación, las pruebas de coagulación, el historial de agentes anti-trombóticos y las comorbilidades. El procedimiento quirúrgico estándar consistió en una trepanación bajo anestesia local, con inserción de un drenaje subdural. Se utilizaron cuestionarios y entrevistas telefónicas para valorar el resultado clínico mediante la Escala de Rankin modificada (mRS). El resultado favorable se definió como el valor de 0 a 3 de mRS, y el resultado desfavorable el valor de 4 a 6. Resultados: Doscientos uno pacientes con HSC fueron sometidos a tratamiento quirúrgico inicial, y fueron incluidos en el estudio. El seguimiento medio fue de 81 semanas. A 41 pacientes (20,4%) se les administró tratamiento anti-plaquetario y a 43 (21,4%) fenprocumón. El hematoma recurrente requirió cirugía en 37 pacientes (18,4%). Se observaron resultados desfavorables en 36 pacientes (17,9%). La avanzada edad y la administración de fenprocumón al ingreso resultaron factores predictivos independientes del resultado desfavorable (p = 0,001 y p = 0,031, respectivamente). La administración de agentes antitrombóticos no tuvo impacto sobre la recidiva del hematoma. Conclusión: La administración de fenprocumón y la edad avanzada pueden incrementar el riesgo de resultado desfavorable en los pacientes con HSC. Ni la administración de fenprocumón ni la de fármacos anti-plaquetarios influyeron en la tasa de hematomas subdurales en nuestra cohorte de pacientes. ˜ ˜ S.L.U. Todos de Neurocirug´ıa. Publicado por Elsevier Espana, © 2017 Sociedad Espanola los derechos reservados.
Introduction The evacuation of chronic subdural hematoma (cSDH) is one of the most common procedures in neurosurgical practice. The procedure is expected to continue to increase in frequency, since cSDH usually occurs in elderly patients and the demographic development in society leads to a rising number of patients over the age of seventy.1 Many of these patients have several comorbidities and are more likely than younger patients to be on antithrombotic drugs at admission, which makes the perioperative management including anesthesia and reversal of antithrombotic drugs more challenging. The pathophysiology behind this disease is wellunderstood and there is consensus that the process of the growing hematoma by continuous reabsorption and re-hemorrhage from the circumjacent membrane has to be disrupted. Local anesthesia and minimal invasive approaches are invaluable, in particular for multimorbid patients. However, the ideal surgical technique remains controversial. Mini-craniotomies as well as single or double burr holes are widely used.2 It is also unclear to what extent intracranial membranes must be resected.3 Further, the benefit of the
insertion of a subdural drainage appears to be unanimous though it remains debatable how long the drainage should be left in situ.4 Although the evacuation of cSDH is considered an easy and safe procedure, recurrence rates up to 33% are reported.5,6 Recurrence is often associated with a longer hospital stay and an unfavorable disease course in the elderly and sometimes multimorbid patients. Several series have analyzed the link between the intake of antithrombotic drugs and hematoma recurrence rates and have reported inconsistent results.7,8 Although there are studies that have evaluated the impact of antithrombotic agents on patients suffering from traumatic brain injury,9,10 few studies have addressed the influence of these medications on the clinical outcome of patients with cSDH. In addition, venous thromboembolism prophylaxis in patients with traumatic brain injury has been addressed in previous studies,11,12 however it has not been discussed in the context of cSDH. In this retrospective series, we introduce the surgical management of cSDH at a single center and investigate the impact of administration of antithrombotic drugs on the clinical outcome of patients surgically treated for cSDH.
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
NEUCIR-303; No. of Pages 7
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
Materials and methods All patients who presented to our department with cSDH proven by CT scan, between June 2008 and June 2013, were identified. Past medical history and neurological function were evaluated and laboratory blood tests were performed at admission. Symptomatic cSDH were assigned to surgical treatment and non-symptomatic cSDH were assigned to conservative treatment. An elevated international normalized ratio (INR) over 1.2 at admission was corrected using vitamin K and prothrombin complex concentrate, while thrombocytopenia was corrected if there was a decrease in platelet count below 50,000 per microliter. Administration of vitamin K in patients of with INR elevation was continued for three days after the procedure. Postoperative blood tests were carried out to monitor INR levels and platelet counts. Patients on antiplatelet medication underwent surgery 5 days after discontinuation of the antiplatelet, unless they were suffering from impaired consciousness, in which case an emergency procedure was performed. Patients who were on phenprocoumon for atrial fibrillation, history of thrombotic embolism in six months prior to admission or for valvular heart disease received a weight adjusted dose of low molecular weight heparin (Enoxaparin sodium; kg*ml/day). Phenprocoumon is a vitamin K antagonist and belongs to the 4-hydroxycoumarins. In some countries as USA and Spain, warfarin, which is another coumarin, is used instead as a vitamin K antagonist. For the prevention of venous thromboembolism, all patients received Enoxaparin sodium 40 mg/day (20 mg/day in case of renal insufficiency) as soon as INR levels were below 1.5. Only patients who were initially treated surgically were included in this study. The data was evaluated retrospectively according to the local ethical standards.
Surgical management and follow-up Surgical treatment was performed under local anesthesia. A minority of incompliant patients or those who were not expected to communicate properly during the procedure received general anesthesia. The supine position without pin fixation was used for all patients. After skin incision, a single burr hole was drilled over the maximum width of the hematoma. After coagulation and incision of the dura matter, the hematoma was washed out with warm irrigation using a Nelaton catheter which was inserted in all directions, if possible. In addition, any visible membranes within the cavity of the hematoma were removed. Before closure, a subdural drain (Jackson-Pratt drain) was left in place whenever possible and then removed after 48 hours. Bed rest in a supine position was recommended for all patients during the first 48 hours postoperatively. CT scans were performed after 48 hours, at 4 weeks, and at 3 and 6 months postoperatively. Recurrent hematomas were treated surgically if they were symptomatic or if they increased in size on follow-up CT scans within 6 months after the procedure.
3
Clinical data Age at surgery, presenting symptoms, administration of antithrombotic agents, history of head trauma, comorbidities, and postoperative complications were assessed by chart reviews. The comorbidities evaluated included diabetes mellitus, atrial fibrillation, arterial hypertension, valvular heart disease ease, coronary heart disease, heart failure and a history of thromboembolic events. Clinical outcome was obtained by questionnaires sent to the patients or telephone interviews and was measured using the modified Rankin Scale (mRS).13 Good outcome was defined as mRS 0 to 3 and poor outcome as mRS 4 to 6.
Statistical analyses According to preoperative administration of antithrombotic agents, patients were divided into 3 subgroups, no antithrombotic agents, antiplatelet drug and phenprocoumon. Comparison between these subgroups regarding age, comorbidities and recurrence rates was performed using Kruskal–Wallis One Way Test and Fisher Exact Test. Logistic regression was used to identify potential prognosticating factors associated with poor outcome. For all tests, a p-value less than 0.05 was considered significant. Statistical analysis and graphics were performed using IBM SPSS Statistics (v20, IBM Corp, Armonk, New York, USA), Microsoft Excel (2013, Microsoft Inc, Seattle, Washington, USA) and SigmaPlot (v12.5, Systat Software Inc, Erkrath, Germany).
Results 249 patients were treated for cSDH at one center during the study period (2008–2013). 201 patients were initially assigned for surgical treatment, were available for follow-up and could be included in this study. 48 patients were excluded from the study, either because they were initially treated conservatively or because they refused surgical treatment. 18 patients died after the procedure within a mean interval of 41 weeks (range 2 to 161 weeks). 5 patients died within 3 weeks after surgery due to postoperative complications including pneumonia, status epilepticus and recurrent bleeding. One patient with a recurrent hemorrhage died 11 weeks after surgery. All other deaths occurred beyond the last CT scan which was performed 6 months after surgery and the leading cause to death was indeterminate. The mean followup period in the remaining patients was 81 weeks (range 14 to 242 weeks). The mean age of the 201 patients (61 female and 140 male) was 72 years (range 25 to 95 years) at the time of operation. A history of fall or head trauma was reported in 85 (42.3%) cases with a mean interval of 6 weeks (range 0.5 to 21 weeks). Initial symptoms are presented in Fig. 1.
Antithrombotic agents and coagulation testing Administration of antithrombotic agents was reported in 84 (41.8%) patients upon admission: 38 patients were on aspirin, 3 on clopidogrel, 38 on phenprocoumon, 4 on aspirin plus
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
ARTICLE IN PRESS
NEUCIR-303; No. of Pages 7
4
n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
Seizures Balance disturbances Vertigo
6
5 5
5 15
4
Speech disorders
24
Impaired consciousness Headache
mRS
37 58
Limb weakness Number of patients 0
3 2
98
20
40
60
80
100
120
1 0
Fig. 1 – Presenting symptoms.
phenprocoumon, and 1 on clopidogrel plus phenprocoumon. In laboratory studies, 47 patients showed elevated INR values and 6 patients showed thrombocytopenia, which were corrected accordingly prior to the surgical procedure. No further correction of platelet count was necessary postoperatively. Because of impaired consciousness in 4 patients who were on antiplatelet medication, the procedure was performed immediately without the usual 5-day interval. Patient characteristics and comorbidities according to the administration of antithrombotic agents are summarized in Table 1. Postoperatively, unless there was proof of recurrent hematoma, administration of antiplatelet medication was continued after 2 weeks interval and administration of phenoprocoumon was continued after 4 weeks interval.
Surgical procedure and clinical outcome In 190 (94.5%) cases, surgery was performed under local anesthesia and in 11 cases (5.5%) it was performed under general anesthesia. 183 (91%) patients had an unilateral hematoma and underwent therefore a single burr hole, while 18 patients (9%) had bilateral hematomas and required two burr holes bilaterally. The procedure-related morbidity was estimated at 4.5% and mortality at 0.5%. 38 patients (18.9%) developed a recurrent hematoma after a mean of 25 days (range 1 to 126 days), one patient underwent a conservative management and 37 patients (18.4%) underwent a second procedure to evacuate the recurrent hematoma, Table 1. The second procedure was performed through the
< 70 years N=142
Patient age
=> 70 years N=59
Fig. 2 – Clinical outcome according to patient age. existing burr hole, except in two patients who received a new burr hole. 5 patients suffered a second recurrence und were consequently operated on a third time. At follow-up, good outcome was found in 165 (82.1%) patients and poor outcome was found in 36 patients (17.9%). Fig. 2 demonstrates clinical outcome using mRS according to patient age.
Comparison and statistical analysis Patient age and rate of comorbidities in the subgroup of patients with antiplatelet medication didn’t differ significantly from those in the subgroup with phenprocoumon, but were significantly higher in both subgroups than in the subgroup without antithrombotic agents (p = <0.001). No correlation between initial symptoms and patient outcome was observed (p = 0.204). None of the comorbidities had influence on clinical outcome (p = 0.067, OR 2.8, 95% CI 0.9–8.3). Recurrence of hematoma had no influence on clinical outcome (p = 0.59, OR 1.2, 95% CI 0.53–3.1). The intake of phenprocoumon was an independent predictor of poor outcome (p = 0.031, Odds ratio (OR) 2.1, 95% Confidence interval (CI) 1.0–4.3). Administration of antiplatelet drug had no measurable influence on outcome (p = 0.135, OR 1.9, 95% CI 0.8–4.7). Older patient age (> 72 years) at the time of operation was associated with a poor outcome, (p = 0.001), Table 2. Neither patient age, nor administration of antiplatelet medication or phenprocoumon had an impact on recurrent hematomas (p = 0.9, 0.7 and 0.2, respectively).
Table 1 – Patients characteristics, comorbidities and recurrence rates according to the administration of antithrombotic agents. Antithrombotic agent
Number of patients Mean age (years) Cardiovascular comorbidities Aortic valve disease Diabetes mellitus Heart failure Recurrence rate
Single antiplatelet agent
Phenprocoumon
None
41 77 29%
43 80 28%
117 70 3%
5% 17% 2% 20%
7% 16% 7% 26%
0% 10% 3% 15%
Table 2 – Predictive factors of poor outcome in patients with cSDH.
Platelet aggregation inhibitor Phenprocoumon Recurrence Comorbidities Age at operation Presenting symptoms
p-value
Odds ratio
Confidence Interval
0.135
1.9
0.8–4.7
0.031 0.536 0.067 0.001 0.204
2.4 1.3 2.8 1.1 –
1.1–5.4 0.6–3.0 0.9–8.3 1.0–1.1 –
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
NEUCIR-303; No. of Pages 7
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
Discussion Mortality and morbidity In this retrospective study, we evaluated the data of 201 patients who were operated for cSDH using a single burr hole with subdural drain. Although the mean age of 72 years in our patient cohort was similar to other studies,14–16 the estimated perioperative mortality rate of 0.5% in our series seems to be low comparing with previous studies, which have mortality rates reported between 2.75% and 13.3%.14,16–18 However, the estimated perioperative morbidity rate of 4.5% in the current series is close to the rates reported in the literature. A recurrent hematoma was found in 18.9% of our patients, which is in line with previous studies that included patient numbers similar to that of our study and reported recurrence rates between 17% and 24%.2,7,8,17,19–21 These results confirm the safety of a single burr hole under local anesthesia, as well as the use of a Nelaton catheter to evacuate the hematoma and the placement of subdural drain for treatment of cSDH.
Antiplatelet and anticoagulant agents Administration of antiplatelet or anticoagulant drugs was not a predictor of recurrent hematoma. This finding is a matter of controversy in the literature, as some studies found that the administration of anticoagulants is predictive of recurrence,8,19,22,23 while others did not find any effect of antiplatelet or anticoagulant therapy on recurrence rate.7,20,24 It is difficult to compare these studies, as they used different surgical techniques to evacuate the hematoma. Many studies have addressed the clinical outcome of patients with cSDH and the factors that were found to predict a poor outcome included older age,14,19,25 lower GCS at admission and recurrent hematoma.19 None of these series found an impact of antiplatelet or anticoagulant agents on clinical outcome. Administration of antiplatelet agents didn’t influence the outcome in the current series, while administration of phenprocoumon was an independent risk factor of poor outcome. This association has not been reported in the literature to date in the context of cSDH. Foerch et al. presented similar finding regarding intracerebral hemorrhage, as they found that in contrast to oral anticoagulants, pre-treatment with antiplatelet agents is not an independent risk factor of mortality and unfavorable outcome in patients with intracerebral hemorrhage.26 Grandhi et al. found that the pre-injury use of warfarin, but not antiplatelet agents, increased mortality in elderly traumatic brain injury patients.10 Inui et al. evaluated risk factors for mortality after presentation with a groundlevel fall among patients with and without anticoagulant agents and concluded that elderly patients on anticoagulant agents for atrial fibrillation and/or flutter who fall have a greater risk for mortality.9 Also, patients with isolated traumatic subarachnoid hemorrhage and elevated INR were found to be at higher risk of clinical deterioration.27 Trauma patients and patients undergoing neurosurgical procedures are at high risk for venous thromboembolism.12,28 Therefore, venous thromboembolism prophylaxis in patients
5
with cSDH is recommended, especially when anticoagulant agents have been withdrawn perioperatively. Although low molecular weight heparin has not been evaluated regarding its impact on cSDH, there are many studies that have evaluated its use after traumatic brain injury and found no significant risk of expanding intracranial hemorrhage.29,30 Phenprocoumon as a vitamin K antagonist causes the inhibition of synthesis of coagulation factors II, VII, IX and X. The annual rates of major bleeding in patients on vitamin K antagonists in daily care are estimated at up to 8%.31 Incidence of cSDH has been reported to be elevated in patients who are on aspirin or warfarin (another vitamin K antagonist).32 Since the administration of anticoagulant agents in most patients is linked to serious comorbidities, especially cardiac diseases. Administration of anticoagulants in this series did not correlate with a higher recurrence rate, nevertheless it was associated with a poor outcome, which might be attributed either to a rebleeding that was not detected because it happened beyond the last scheduled CT scan 6 months after surgery or due to other systemic bleeding complications that were not included in our analysis; neurosurgeons have to be aware of the impact of these medications on treatment and outcome of patients with supposedly an easily-treated pathology such as chronic subdural hematoma, and might consider a longer follow-up period in older patients and those who are on anticoagulant medication. In addition, neuro- and trauma surgeons should be aware of many new antithrombotic agents, which are increasingly implemented in daily practice, as their influence on intracranial hemorrhage is still unknown.
Limitations Our results, especially the correlation between the administration of phenprocoumon and poor outcome in patients operated for cSDH, must be interpreted carefully due to the retrospective nature of this study and the wide range of followup periods. Larger series will be necessary to confirm our findings.
Conclusions Administration of phenprocoumon in patients with cardiovascular comorbidities and older age might be predictive of poor outcome in patients with cSDH, while administration of antiplatelet drug did not seem to have an impact on clinical outcome. Neither the administration of phenprocoumon nor single platelet inhibitors influenced the recurrence of subdural hematoma in our patient cohort.
Ethical approval All procedures performed in this study were in accordance with the ethical standards of the local ethics committee and with the 1964 Helsinki declaration and its later amendments.
Conflict of interest The authors have no conflicts of interest to declare.
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
NEUCIR-303; No. of Pages 7
6
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
references
1. Kudo H, Kuwamura K, Izawa I, Sawa H, Tamaki N. Chronic subdural hematoma in elderly people: present status on Awaji Island and epidemiological prospect. Neurol Med Chir (Tokyo). 1992;32:207–9. 2. Pahatouridis D, Alexiou GA, Fotakopoulos G, Mihos E, Zigouris A, Drosos D, et al. Chronic subdural haematomas: a comparative study of an enlarged single burr hole versus double burr hole drainage. Neurosurg Rev. 2013;36:151–4, http://dx.doi.org/10.1007/s10143-012-0412-3 [discussion 154–5]. 3. Rocchi G, Caroli E, Salvati M, Delfini R. Membranectomy in organized chronic subdural hematomas: indications and technical notes. Surg Neurol. 2007;67:374–80, http://dx.doi.org/10.1016/j.surneu.2006.08.066. 4. Santarius T, Kirkpatrick PJ, Ganesan D, Chia HL, Jalloh I, Smielewski P, et al. Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial. Lancet. 2009;374:1067–73, http://dx.doi.org/10.1016/S0140-6736(09)61115-6. 5. Taussky P, Fandino J, Landolt H. Number of burr holes as independent predictor of postoperative recurrence in chronic subdural haematoma. Br J Neurosurg. 2008;22:279–82, http://dx.doi.org/10.1080/02688690701818885. 6. Wakai S, Hashimoto K, Watanabe N, Inoh S, Ochiai C, Nagai M. Efficacy of closed-system drainage in treating chronic subdural hematoma: a prospective comparative study. Neurosurgery. 1990;26:771–3. 7. Aspegren OP, Astrand R, Lundgren MI, Romner B. Anticoagulation therapy a risk factor for the development of chronic subdural hematoma. Clin Neurol Neurosurg. 2013;115:981–4, http://dx.doi.org/10.1016/j.clineuro. 2012.10.008. 8. Chon KH, Lee JM, Koh EJ, Choi HY. Independent predictors for recurrence of chronic subdural hematoma. Acta Neurochir (Wien). 2012;154:1541–8, http://dx.doi.org/10.1007/s00701-012-1399-9. 9. Inui TS, Parina R, Chang DC, Inui TS, Coimbra R. Mortality after ground-level fall in the elderly patient taking oral anticoagulation for atrial fibrillation/flutter: a long-term analysis of risk versus benefit. J Trauma Acute Care Surg. 2014;76:642–9, http://dx.doi.org/10.1097/ta.0000000000000138 [discussion 649–50]. 10. Grandhi R, Harrison G, Voronovich Z, Bauer J, Chen SH, Nicholas D, et al. Preinjury warfarin, but not antiplatelet medications, increases mortality in elderly traumatic brain injury patients. J Trauma Acute Care Surg. 2015;78:614–21, http://dx.doi.org/10.1097/ta.0000000000000542. 11. Foreman PM, Schmalz PG, Griessenauer CJ. Chemoprophylaxis for venous thromboembolism in traumatic brain injury: a review and evidence-based protocol. Clin Neurol Neurosurg. 2014;123:109–16, http://dx.doi.org/ 10.1016/j.clineuro.2014.05.017. 12. Barrera LM, Perel P, Ker K, Cirocchi R, Farinella E, Morales Uribe CH. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev. 2013;3:Cd008303, http://dx.doi.org/ 10.1002/14651858.CD008303.pub2. 13. Banks JL, Marotta CA. Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. Stroke. 2007;38:1091–6, http://dx.doi.org/10.1161/01.STR.0000258355.23810.c6. 14. Gelabert-Gonzalez M, Iglesias-Pais M, Garcia-Allut A, Martinez-Rumbo R. Chronic subdural haematoma: surgical treatment and outcome in 1000 cases. Clin Neurol Neurosurg. 2005;107:223–9, http://dx.doi.org/10.1016/j.clineuro. 2004.09.015.
15. Grobelny BT, Ducruet AF, Zacharia BE, Hickman ZL, Andersen KN, Sussman E, et al. Preoperative antiepileptic drug administration and the incidence of postoperative seizures following bur hole-treated chronic subdural hematoma. J Neurosurg. 2009;111:1257–62, http://dx.doi.org/10.3171/ 2009.6.jns0928. 16. Leroy HA, Aboukais R, Reyns N, Bourgeois P, Labreuche J, Duhamel A, et al. Predictors of functional outcomes and recurrence of chronic subdural hematomas. J Clin Neurosci. 2015, http://dx.doi.org/10.1016/j.jocn.2015.03.064. 17. Borger V, Vatter H, Oszvald A, Marquardt G, Seifert V, Guresir E. Chronic subdural haematoma in elderly patients: a retrospective analysis of 322 patients between the ages of 65-94 years. Acta Neurochir (Wien). 2012;154:1549–54, http://dx.doi.org/10.1007/s00701-012-1434-x. 18. Rohde V, Graf G, Hassler W. Complications of burr-hole craniostomy and closed-system drainage for chronic subdural hematomas: a retrospective analysis of 376 patients. Neurosurg Rev. 2002;25:89–94. 19. Amirjamshidi A, Abouzari M, Eftekhar B, Rashidi A, Rezaii J, Esfandiari K, et al. Outcomes and recurrence rates in chronic subdural haematoma. Br J Neurosurg. 2007;21:272–5, http://dx.doi.org/10.1080/02688690701272232. 20. Lindvall P, Koskinen LO. Anticoagulants and antiplatelet agents and the risk of development and recurrence of chronic subdural haematomas. J Clin Neurosci. 2009;16:1287–90, http://dx.doi.org/10.1016/j.jocn.2009.01.001. 21. Nakaguchi H, Tanishima T, Yoshimasu N. Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. J Neurosurg. 2001;95:256–62, http://dx.doi.org/10.3171/jns.2001.95.2.0256. 22. 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;88:1889–93, http://dx.doi.org/10.1212/wnl. 0000000000003918. 23. Wang Y, Zhou J, Fan C, Wang D, Jiao F, Liu B, et al. Influence of antithrombotic agents on the recurrence of chronic subdural hematomas and the quest about the recommencement of antithrombotic agents: a meta-analysis. J Clin Neurosci. 2017;38:79–83, http://dx.doi.org/10.1016/j.jocn.2016.12. 001. 24. Ohba S, Kinoshita Y, Nakagawa T, Murakami H. The risk factors for recurrence of chronic subdural hematoma. Neurosurg Rev. 2013;36:145–9, discussion 149-50, http://dx.doi.org/10.1007/s10143-012-0396-z 25. Pilitsis J, Atwater B, Warden D, Deck G, Carroll J, Smith J, et al. Outcomes in octogenarians with subdural hematomas. Clin Neurol Neurosurg. 2013;115:1429–32, http://dx.doi.org/ 10.1016/j.clineuro.2013.01.017. 26. Foerch C, Sitzer M, Steinmetz H, Neumann-Haefelin T. Pretreatment with antiplatelet agents is not independently associated with unfavorable outcome in intracerebral hemorrhage. Stroke. 2006;37:2165–7, http://dx.doi.org/ 10.1161/01.str.0000231842.32153.74. 27. von der Brelie C, Schneegans I, van den Boom L, Meier U, Hedderich J, Lemcke J. Impaired coagulation is a risk factor for clinical and radiologic deterioration in patients with traumatic brain injury and isolated traumatic subarachnoid hemorrhage. J Trauma Acute Care Surg. 2015;79:295–300, http://dx.doi.org/10.1097/ta.0000000000000722. 28. Browd SR, Ragel BT, Davis GE, Scott AM, Skalabrin EJ, Couldwell WT. Prophylaxis for deep venous thrombosis in neurosurgery: a review of the literature. Neurosurg Focus. 2004;17:E1, http://dx.doi.org/10.3171/foc.2004.17.4.1. 29. Dudley RR, Aziz I, Bonnici A, Saluja RS, Lamoureux J, Kalmovitch B, et al. Early venous thromboembolic event prophylaxis in traumatic brain injury with low-molecular-weight heparin: risks and benefits.
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006
NEUCIR-303; No. of Pages 7
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 7;x x x(x x):xxx–xxx
J Neurotrauma. 2010;27:2165–72, http://dx.doi.org/10.1089/ neu.2010.1366. 30. Phelan HA, Wolf SE, Norwood SH, Aldy K, Brakenridge SC, Eastman AL, et al. A randomized, double-blinded, placebo-controlled pilot trial of anticoagulation in low-risk traumatic brain injury: the Delayed Versus Early Enoxaparin Prophylaxis I (DEEP I) study. J Trauma Acute Care Surg. 2012;73:1434–41, http://dx.doi.org/10.1097/TA. 0b013e31825ac49e.
7
31. Beyer-Westendorf J, Forster K, Pannach S, Ebertz F, Gelbricht V, Thieme C, et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood. 2014;124:955–62, http://dx.doi.org/ 10.1182/blood-2014-03-563577. 32. Rust T, Kiemer N, Erasmus A. Chronic subdural haematomas and anticoagulation or anti-thrombotic therapy. J Clin Neurosci. 2006;13:823–7, http://dx.doi.org/10.1016/ j.jocn.2004.12.013.
Please cite this article in press as: Abboud T, et al. Influence of antithrombotic agents on recurrence rate and clinical outcome in patients operated for chronic subdural hematoma. Neurocirugia. 2017. https://doi.org/10.1016/j.neucir.2017.09.006