The influence of preoperative anticoagulation on outcome and quality of life after surgical treatment of chronic subdural hematoma

Journal of Clinical Neuroscience 17 (2010) 975–979

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Clinical Study

The influence of preoperative anticoagulation on outcome and quality of life after surgical treatment of chronic subdural hematoma M.T. Forster *, A.K. Mathé, C. Senft, I. Scharrer, V. Seifert, R. Gerlach Department of Neurosurgery, Goethe University Frankfurt am Main, Schleusenweg 2-16, D-60528 Frankfurt am Main, Germany

a r t i c l e

i n f o

Article history: Received 26 October 2009 Accepted 24 November 2009

Keywords: Anticoagulation Chronic subdural hematoma Outcome Quality of life Surgery

a b s t r a c t The main aim of this study was to investigate the influence of perioperative anticoagulation on the clinical course and outcome of 144 patients who underwent surgery for chronic subdural hematoma (CSDH). The outcome was categorized according to the modified Rankin Scale (mRS), Barthel Index and postoperative quality of life (QoL) scale. There was a significant correlation between preoperative aspirin medication and reoperation (Mann–Whitney U-test, p < 0.05). Moreover, dosage and duration of postoperative low-molecular-weight heparin (LMWH) administration were associated with a higher risk of reoperation (Mann–Whitney U-test, p < 0.01) and a worse outcome on the mRS (Mann–Whitney Utest, p < 0.05). Intraoperative treatment with prothrombin complex concentrate led to a poor outcome on the mRS (Craddock-Flood test, p < 0.05). Reoperation is the strongest predictive factor of a poor QoL after surgical treatment of CSDH. Both preoperative and postoperative anticoagulation treatment may affect reoperation rate and, thus, postoperative QoL. Ó 2010 Elsevier Ltd. All rights reserved.

1. Introduction Chronic subdural hematoma (CSDH) is a common disease in neurosurgical practice with an incidence of about 8/100,000 per year; it mainly affects the elderly, with a male-to-female ratio of 2.5:1.1–6 Treatment options consist of burr hole trepanation or craniotomy. While minimally invasive procedures usually suffice, open craniotomies may be necessary for certain patients. In 1857, Virchow postulated that a pachymeningitis hemorrhagica interna was the origin of CSDH.7 Half a century later, in 1914, Trotter considered the bleeding to be of traumatic and venous origin.8 His theory became increasingly accepted, even for patients with inapparent trauma, and it remains the accepted cause for most patients. A history of head injury can be identified in 50% to 80% of the patients suffering from CSDH. However, other causes such as chronic alcoholism (6–14%), and the widespread use of anticoagulation and antiplatelet therapy, also have an important role in the pathogenesis of CSDH.2,4,5,9–13 Abnormalities in coagulation may also account for the increase in, or recurrence of, CSDH after surgery. Thus, clotting factors, sometimes already decreased by coagulopathy or inhibited by anticoagulation therapy, may be subjected to postoperative decrease, allowing increase in or recurrence of CSDH.3,12 Therefore, this study aims to determine the effect of perioperative anticoagulation

* Corresponding author. Tel.: +49 69 6301 5939; fax: +49 69 6301 7175. E-mail address: [email protected] (M.T. Forster). 0967-5868/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2009.11.023

medication on the clinical course, the postoperative outcome and the quality of life after surgical treatment of CSDH. 2. Materials and methods Data from 144 patients consecutively admitted for treatment of CSDH were analysed retrospectively. Surgical treatment was performed at the Department of Neurosurgery, Goethe University Frankfurt am Main. Medical data and information on the clinical course were obtained from patient charts and surgical evacuation, which was usually performed using a single burr hole for drainage of the hematoma. Patients who had suspected septation underwent a small craniotomy. The method of surgical evacuation was determined by the surgeon performing the operation. Long-term outcome (at least 6 months after surgical treatment) was assessed by questionnaires or telephone interviews. 2.1. Coagulation testing and replacement algorithm Coagulation parameters including platelets, partial thromboplastin time (PTT), prothrombin time (PT), international normalized ratio (INR), fibrinogen and antithrombin (AT) were routinely tested before surgical procedures. The institutional protocol was aimed at maintaining platelets >100  10 9/L, PTT < 40 s, PT > 60%, fibrinogen >1.5 g/L and AT > 70%. Therefore, if deficiencies were detected by a preoperative analysis, prothrombin complex concentrate (PCC), fresh frozen plasma (FFP), platelet concentrates, fibrinogen or AT were administered to normalize the coagulation profile.

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2.2. Assessment of outcome-related factors Patient charts were examined for the following variables: more than one previous head injury, side of CSDH, acute bleeding and septation of the hematoma, and anticoagulation medication. The clinical course was evaluated for recurrence and surgical revision; the patient medical histories were assessed for concomitant diseases and medication. Special attention was given to preoperative and intraoperative treatment of coagulation abnormalities. The subjective bleeding tendency was determined by a questionnaire completed by the patients and/or their relatives. 2.3. Outcome assessment and quality of life Outcome was rated using a multiple-choice questionnaire designed to calculate the Barthel Index (BI), the modified Rankin Scale (mRS) score and the quality of life (QoL) scale.14–18 It also contained a scale for self-assessment of the actual state of health. The outcome was considered poor if a patient had a BI of 6 95 and an mRS of >1. The QoL scale was based on the Sickness Impact Profile (SIP), which was modified by van Straten for stroke patients, and consisted of 30 items in eight categories.19 With a range from 0% to 100% (the latter being maximal dysfunction), the scores include the psychosocial and physical consequences of illness. Additionally, the patient’s self-evaluation of the actual state of health was assessed using a scale where the patient had to mark one point on a line between 0 (death or severe disability) and 100 (completely healthy). 2.4. Statistical analysis Statistical analysis was performed using the Mann–Whitney Utest, the chi-squared (v2) test, the Craddock-Flood modification and the logistic regression model. The Mann–Whitney U-test was used to determine the correlation between patient age, time between trauma, diagnosis and surgery, dosage and duration of low-molecular-weight heparin (LMWH), and various blood parameters with the outcome. This test was also employed for the statistical analysis of QoL. By applying the v2 test, patient sex, etiology of CSDH, subjective bleeding tendency and assessment of a second trauma, as well as the administration of substitution therapy, were related to the mRS score. Where there were small samples of investigated items that included up to five characteristics, the Craddock-Flood modification of the v2 test was used. The timing of substitution therapy, as well as different postoperative medications, were correlated with the outcome. A multivariate analysis using the logistic regression model completed the investigation; all statistical results were considered significant if p < 0.05. 3. Results 3.1. Demographical characteristics The patient sample consisted of 44 women and 100 men with a median age of 72.0 years (range: 17–95 years; Fig. 1). CSDH was located on the right side in 51 patients (35.4%), on the left side in 62 patients (43.1%) and bilaterally in the remaining 31 patients (21.5%). A CT scan showed acute bleeding into the CSDH in 49 participants (34%). Septation was observed in 24 individuals (16.7%). Five patients died within the period of hospitalization, six during the 12 months after discharge and one patient was of no fixed address and was therefore lost to follow-up. As a result, questionnaires were sent to 132 patients. Completed questionnaires were received from 71 patients (54%), 22 were interviewed by telephone

and eight had a follow-up examination in the hospital’s outpatient department. Information on the remaining 31 patients was obtained from the primary letter of discharge from our department. Trauma as the cause of the CSDH was found in 96 of 144 patients (66.7%). A second trauma was recalled by 39 patients (27%). The interval between trauma and diagnosis was 37.2 ± 32 days (range, 7–180 days). Surgery was performed after 45.9 ± 33.6 days. Assessment of co-morbidities revealed an oncological disease in 11 patients and chronic alcoholism in six patients; arterial hypertension was diagnosed in a total of 67 patients. A subjective bleeding tendency was documented in eight patients. 3.2. Surgical results and reoperation Burr hole trepanation was performed on 85 patients (59%) and craniotomy in 52 (36.1%). Seven patients (4.9%) underwent craniotomy on one side and burr hole trepanation on the other. Reoperation was necessary in 34 patients (23.6%); of these, only four (2.7%) required that a burr hole trepanation be extended into a craniotomy during the second operation. Three patients required more than one reoperation. One patient suffered from kidney failure, and subsequently needed dialysis and developed impaired coagulation. Another patient had been treated preoperatively with phenprocoumon due to coronary heart disease, necessitating treatment with FFP, PCC and AT over 5 weeks. For a third patient, the cause of CSDH recurrence remained unclear. Preoperative medication with aspirin was associated with recurrence of the hematoma requiring reoperation (p < 0.05). Of the 38 patients who were prescribed preoperative aspirin, 12 needed a second operation; these individuals had usually taken their last dose of aspirin within the 24 hours (0.75 ± 2 days) prior to the procedure. In the remaining 26 patients, aspirin administration had been suspended at about 2 days (2.08 ± 2.7 days) before surgery. The risk of reoperation also increased significantly with the duration and dose of postoperative application of LMWH (nadroparin; molecular weight 4500 daltons). Altogether, 66 patients were postoperatively treated using LMWH; of these, 22 (33%) had to undergo reoperation while the remainder did not, with a median duration of LMWH treatment of 18 days and 10 days, respectively (Mann–Whitney U-test, p < 0.01). The daily median dosage of LMWH was 5700 IU in the patients who required reoperation and 2850 IU for those who did not (Mann–Whitney Utest, p < 0.05). The higher dose was administered to patients who had atrial fibrillation, carotid stenosis, or a history of pulmonary embolism or peripheral thrombosis. Patients without these comorbidities were administered the lower dose. 3.3. Outcome using modified Rankin Scale and Barthel Index A total of 11 patients died (five during the hospital stay and six after discharge). A total of 21 patients had a BI score of <100 while 53 had an mRS score >1, considered the worst outcome. Assessment of variables that could influence the outcome revealed that increased age (p < 0.05 in the mRS, p < 0.01 in the BI), female sex (p < 0.01 in the BI), a second trauma (p < 0.05 in the mRS, p < 0.01 in the BI) and hematoma septation (p < 0.05 in the mRS, p < 0.01 in the BI) were associated with a worse outcome. However, the presence of acute bleeding had no influence on the outcome (p > 0.05). Preoperative laboratory findings had a partial influence on patient outcome. The median INR in patients with good or poor outcome, as measured by the mRS score, varied by only 0.07 (p < 0.01). If patients with an INR < 1.2 only were considered, the INR value in patients with mRS 61 was lower than patients with an mRS >1 (p < 0.05) (Table 1).

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60

Number of patients

50 40 30 20 10 0 18-29

30-39

40-49

50-59 Age

60-69

Men

Women

70-79

80-89

90-99

Fig. 1. Age (in years) and sex of 144 patients who had chronic subdural hematoma. Most patients were older than 70 years.

The same holds true of the PT, where patients with a poor mRS score had a median PT of 83.5% ± 19.7%, while a high score was associated with a median PT of 92.4% ± 12.2% (p < 0.01). The AT level was lower in patients who had a worse outcome on the mRS score compared to patients with a mRS score 61 (p < 0.05). The latter had a median AT activity of 102% ± 13.1% in contrast to patients with an mRS result of >1, whose average AT activity was 89.5% ± 12.3% (p < 0.05). Although the red blood cell volume affected only the mRS score (p < 0.01) and the need for reoperation (p < 0.05), reduced preoperative hematocrit and hemoglobin levels were associated with a higher incidence of a second operation (p < 0.05 for both), as well as poor outcome on both the mRS score (p < 0.01 for both) and the BI (p < 0.05 for both (Table 2). The number of thrombocytes had no influence on patient outcome (p > 0.05). In addition, we examined the outcome of patients who underwent treatment with platelet concentrates, FFP, PCC and AT III. Their outcome was compared to that of patients who did not receive any substitution therapy. Patients who underwent substitution therapy had a higher risk of a poorer mRS score outcome (p < 0.05). However, only the intraoperative administration of PCC was responsible for this result, since it was associated with a poorer mRS score (Table 3). Concerning subjective history of bleeding, patients who thought they were more prone to bleeding showed a poorer outcome in both the mRS score (p < 0.05) and the BI (p < 0.01).

Table 2 Effect of red blood cells (RBC) volume, hematocrit (Ht) and hemoglobin (Hb) levels on the mRS score as analysed by the Mann–Whitney U-test mRS 61 n = 75

>1 n = 43

Table 1 Effect of preoperative INR on mRS score as analysed by the Mann-Whitney U-test

INR (median)

INR P 1.2

mRS 6 1

mRS > 1

n = 62 1.03

n = 30 1.07

p = 0.0212

INR (median)

No n = 75

4.54 4.14 p = 0.0005

4.55 5.38 p = 0.0556

4.62 4.4 p = 0.0433

Ht (%) (median)

41.2 37.6 p = 0.00008

41.35 38 p = 0.024

41.8 40.5 p = 0.0381

Hb (g/dL) (median)

14.1 12.7 p = 0.00002

14.2 12.9 p = 0.0207

14.25 13.6 p = 0.0338

mRS = modified Rankin Scale score.

Table 3 The correlation between temporal administration of PCC and the mRS score, Barthel Index and reoperation as analysed by the Craddock-Flood modification of the chisquared test Administration of PCC

None Preoperative Intraoperative Postoperative

Barthel Index

Reoperation

61

mRS >1

100

<100

Yes

No

77 3 0 2

45 0 3 5

59 3 0 2

20 0 0 1

30 2 1 1

73 1 1 5

p = 0.5711

p = 0.4145

PCC = prothrombin complex concentrate.

The postoperative QoL results were worse in women (p < 0.05), as they did not feel as good as men in dimensions other than intelligence. Patients who had undergone at least two episodes of trauma before the diagnosis of CSDH reported a worse outcome

INR < 1.2

Reoperation Yes n = 28

>100 n = 17

RBC (pL) (median)

p = 0.0194

3.4. Statistical analysis using the quality of life scale

Barthel Index 100 n = 60

mRS 6 1

mRS > 1

n=9 1.24

n = 11 1.28

p = 0.456

INR = international normalized ratio, mRS = modified Rankin Scale score.

in both the physical and psychosocial dimension compared to patients with only one or no episodes of trauma (p < 0.01 for both). Bilateral distribution of CSDH or the coexistence of an acute bleeding component had no effect on QoL. A significant difference in all but the psychological aspect was found in patients who had a subjective bleeding tendency (p < 0.05). Patients who were prone to bleeding felt more restricted in the physical dimension than patients with a subjective normal hemostasis (p < 0.05). Although the surgical technique had no impact on the mRS score outcome, a second operation had a negative effect on the physical dimension of postoperative QoL (p < 0.05). Preoperative anticoagulation therapy, administration of antiplatelet drugs, and substitution therapy had no significant impact on the QoL (Table 4).

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4. Discussion In the study, we analyzed outcome and QoL after surgical treatment of CSDH, with an emphasis on anticoagulation and antiplatelet therapy. Previous investigations have used the Glasgow coma scale (GCS), the Glasgow outcome scale (GOS), the grading system for CSDH by Markwalder or the assessment of recovery, worsening or death to assess the postoperative outcome after CSDH.2–4,10,11,13,20–24 While the mRS is similar to the GOS and describes the functional outcome, the BI focuses on daily activities of life. Both scales do not account for the social and emotional aspects of life. Therefore, we used the SIP to measure QoL after surgical treatment of CSDH.19 To our knowledge, this has never been done before. The mortality after surgical treatment of CSDH ranges from 1.2% to 3.8%.2–5,13,23 Yasuda et al. even describe a mortality of 9.3% of patients treated for this condition.21 In our study, a total of five patients (3.5%) died during or after surgery for CSDH, while another six died after discharge from non-surgery-related causes. One patient, who had a history of alcohol abuse, was comatose and presented with a unilateral fixed pupil prior to an emergency operation; he died during surgery. Additionally, three patients suffered from complications during their postoperative course in the intensive care unit (heart failure, multi-organ dysfunction syndrome and severe septicemia) and died. Another patient died because of coagulation disorders related to leukemia. According to König et al., the outcome of patients with CSDH is dependent on alcohol intake, the recurrence of CSDH and on the postoperative administration of coagulation factors. These factors showed a clear correlation with a worse outcome, as defined by a GCS score < 13.2 We found that the outcome after CSDH was negatively influenced by patient age and whether they were female. Women were more limited in their daily activities of life. A history of more than one episode of trauma before the diagnosis of CSDH led to a poorer outcome in all aspects of our questionnaire assessment. The same

was found for patients who reported an augmented bleeding tendency that did not correlate with antiplatelet or anticoagulation medication. Obviously, this was a subjective impression, and they may have retrospectively judged their bleeding tendency as high. In only one patient was the disposition for increased bleeding tendency confirmed before hospitalization. Pieracci et al. postulated that both mortality and morbidity were increased in warfarin users who had an INR P 2.20 Also, Yasuda et al. reported a higher rate of fatal outcome in patients harbouring an INR P 1.25.21 In our study, 12 patients underwent anticoagulation with phenprocoumon. No correlation could be found between its use and patient outcome, however this might be explained by a strict institutional replacement protocol. Contrarily, in our series, aspirin had an influence on patient outcome. Comparing patients who used aspirin the day before surgery and those who took it the day of their surgery, the latter were more often subjected to reoperation (p < 0.05). O’Brien et al. found that the rate of reoperations was twice as great for patients taking aspirin than those who were not.25 These reoperations had a negative influence on the QoL in our patient population (p < 0.05). In the studies by König et al. and Yasuda et al., preoperative thrombocytopenia was associated with a higher rate of reoperation and mortality.2,21 We were not able to confirm this. However, the red blood cells volume, hemoglobin levels and hematocrit had a significant influence on the outcome on both the mRS and the BI (Table 1). Moreover, the rate of reoperation was clearly correlated with the red blood cell volume, hemoglobin and hematocrit. This is surprising because we anticipated lower values in patients who required reoperation; however, our data showed the opposite. The underlying causes for this observation remain unclear; no comparative data were available in the literature. In instances of hemostatic impairment, which was defined as a platelet count of less than 100  109 platelets/L, PTT > 40 s, PT < 60%, AT < 70% or fibrinogen < 1.5 g/L, the team perioperatively administered replacement therapy for immediate correction. Of

Table 4 Postoperative QoL is affected by sex, the number of episodes of head trauma, the subjective observation of an augmented bleeding disposition and reoperation as analysed by the Mann-Whitney U-test

1 2 3 4 5 6 7 8 9 10 11 12 13

14

Post-op. subjective QoL

Physical dim.

Difference

Psychosocial dim.

Difference

Female Male Age < 70 y Age > 70 y Traumatic CSDH Spontaneous CSDH 2nd trauma No 2nd trauma Unilateral CSDH Bilateral CSDH Acute component No acute component Septation No septation Augmented bleeding disposition (n = 4) No augmented bleeding disposition Preop. anticoagulation or antiplatelet drugs None Postop. anticoagulation or antiplatelet drugs None Substitution therapy None Burr hole trepanation Craniotomy (unilateral CSDH) Bilateral CSDH, 1 burr hole Bilateral CSDH burr hole + craniotomy Bilateral CSDH, craniotomy Reoperation No reoperation

27.76 13.22 12.8 22.3 18.08 18.23 29.26 10.27 19.09 14.51 17.64 16.94 23.1 16 60.55 18.13 20.15 15.14 22.97 11.38 10.75 18.62 19.39 15.27 16.73 15.33 0 32.09 13.56

p = 0.0409

16.45 10.78 13.8 11.8 13.75 10.37 18.07 7.75 13.02 11.31 9 12.1 15.7 11.4 29.75 12.66 13.14 11.69 14.36 10.52 7.8 12.98 13.58 12.24 9.98 24.17 0 19.45 10.45

p = 0.2745

p = 0.0753 p = 0.9722 p = 0.0102 p = 0.4649 p = 0.6597 p = 0.6799 p = 0.0012 p = 0.5158 p = 0.0545 p = 0.6660 p = 0.4964 p = 0.9451

p = 0.0419

CSDH = chronic subdural hematoma, Dim. = dimension, preop. = preoperative, postop. = postoperative, QoL = quality of life, y = years.

p = 0.7949 p = 0.6250 p = 0.0088 p = 0.5929 p = 0.8378 p = 0.5783 p = 0.0594 p = 0.2683 p = 0.1910 p = 0.6956 p = 0.7112 p = 1.00

p = 0.0710

M.T. Forster et al. / Journal of Clinical Neuroscience 17 (2010) 975–979

the patients who were treated with phenprocoumon in this study, 10 received PCC (6.9%). In the study of König et al., 14% of 114 patients were treated with PCC prior to surgery.2 They described that the outcome of these patients was the same as that of patients without PCC replacement, which was confirmed by this study. However, they also observed a worse outcome in patients who received postoperative replacement therapy, which we did not observe.2 Only intraoperative administration of PCC (eight patients) was correlated to a worse outcome according to the mRS (p < 0.05). The surgical procedure consisted of a craniotomy and/or burr hole trepanation. Among the 54 patients who underwent craniotomy, most reported a better QoL than those patients who underwent a single burr hole trepanation, although the difference was not statistically significant. Assuming that burr hole trepanation is less invasive than craniotomy, it appears that this improved QoL results from a secondary benefit of illness due to prolonged postoperative care after craniotomy. Moreover, a larger wound is generally associated with better treatment and better results. Obviously our study has a number of limitations. The first assessment was performed retrospectively, and data was obtained from patients notes and a self-reporting questionnaire. Interpretation of the postoperative QoL data is particularly difficult, since these reflect the subjectively reported QoL, which cannot be readily evaluated in an objective way. The measurement of QoL needs to be considered in relation to the preoperative state, which is difficult to assess before the sudden onset of any neurological symptoms. However, our study attempts to assess the QoL after surgical evacuation of CSDH, which, of course, should be continued over the following years. 5. Conclusion The number of neurosurgical patients taking medication that interferes with platelet function and/or the coagulation system has increased over the years. This is reflected by the large number of patients suffering from CSDH associated with the use of antiplatelet medication and anticoagulant therapy. Not only the outcome assessed by conventional measures such as GCS, mRS and GOS scores, but also the functional status (BI) and, moreover, the QoL can be influenced by such therapeutic regimes, which need to be considered during the treatment of patients with CSDH. Therefore, our study aims to determine the effect of perioperative anticoagulation medication on the clinical course, postoperative outcome and QoL after surgical treatment of CSDH. Acknowledgment The authors are grateful to Dr. Hanns Ackermann of the Institute of Biostatistics, Goethe University, Frankfurt am Main, Germany, for helping to perform the statistical calculations.

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