- Email: [email protected]
Clinical outcomes in patients on preinjury ibuprofen with traumatic brain injury
The American Journal of Surgery (2014) -, -–-
Clinical outcomes in patients on preinjury ibuprofen with traumatic brain injury Bardiya Zangbar, M.D., Viraj Pandit, M.D., Peter Rhee, M.D., Mazhar Khalil, M.D., Narong Kulvatunyou, M.D., Terence O’Keeffe, M.B., Ch.B., Andrew Tang, M.D., Lynn Gries, M.D., Donald J. Green, M.D., Randall S. Friese, M.D., Bellal Joseph, M.D.* Division of Trauma, Department of Surgery, University of Arizona, Tucson, AZ, USA
KEYWORDS: Ibuprofen; Motrin; Nonsteroidal antiinflammatory drugs; Traumatic brain injury; Repeat head computed tomography; Neurosurgical Intervention
Abstract BACKGROUND: The aim of our study was to evaluate the clinical outcomes in patients on preinjury Ibuprofen with traumatic brain injury. METHODS: We performed a 2-year analysis of all patients on prehospital Ibuprofen with traumatic brain injury and intracranial hemorrhage. Patients on preinjury Ibuprofen were matched using propensity score matching to patients not on Ibuprofen in a 1:2 ratio for age, Glasgow Coma Scale, headabbreviated injury scale, injury severity score, International Normalized Ratio, and neurologic examination. Outcome measures were progression on repeat head computed tomography (RHCT) and neurosurgical intervention. RESULTS: A total of 195 matched (Ibuprofen 65, no-Ibuprofen 130) patients were included. There was no difference in the progression on RHCT (Ibuprofen 18% vs no-Ibuprofen 24%; P 5 .50). The neurosurgical intervention rate was 18.9% (n 5 37). There was no difference for need for neurosurgical intervention (26% vs 16%; P 5 .10) between the 2 groups. CONCLUSIONS: In a matched cohort of trauma patients, preinjury Ibuprofen use was not associated with progression of initial intracranial hemorrhage and the need for neurosurgical intervention. Preinjury use of Ibuprofen as an independent variable should not warrant the need for a routine RHCT scan. Published by Elsevier Inc.
Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute one of the most widely used class of drugs, with more than 70 million prescriptions and more than 30 billion over-
There were no relevant financial relationships or any sources of support in the form of grants, equipment, or drugs. Oral presentation at the 66th Annual Southwestern Surgical Congress, April 13–16, 2014, Scottsdale, Arizona. * Corresponding author. Tel.: 11-520-626-5056; fax: 11-520-6265016. E-mail address: [email protected] Manuscript received May 1, 2014; revised manuscript May 11, 2014
0002-9610/$ - see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.amjsurg.2014.05.027
the-counter tablets sold annually in the United States.1 Many people take Ibuprofen or other NSAIDs for rheumatic disorders, headache, musculoskeletal problem, and pain control. The antiplatelet effect of nonsalicylate NSAIDs such as Ibuprofen as a reversible cyclooxygenase inhibitor has been widely assessed in both in vitro and in vivo studies.2–4 Based on these studies, they are often withdrawn 7 or more days before surgery to avoid potential bleeding complications.5 With the increase in trends of medical treatment by NSAIDs among US population,6 a greater proportion of the traumatic brain injury (TBI) patients are visiting trauma
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centers with a positive medical history of NSAIDs. However, studies focusing on TBI either exclude the patients on NSAIDs or combine them with all other preinjury medications with antiplatelet effect in a single group and evaluate them as a single variable.7–11 A recent study suggests that preinjury NSAID therapy reduces trauma-induced coagulopathy.12 However, despite the antiplatelet effect of these drugs, there is a paucity of literature studying this effect on the clinical outcomes of the patients with TBI on preinjury NSAID therapy. The aim of our study was to evaluate the effect of preinjury Ibuprofen on outcomes (progression and neurosurgical intervention) in patients with TBI.
Ibuprofen (no-Ibuprofen group) in a 1:2 ratio for age, GCS, systolic blood pressure, heart rate, h-AIS score, ISS, neurologic examination, INR, type and size of the ICH, and skull fracture. Propensity matching is an analog to the process of randomization of a clinical trial that is commonly used for dealing with selection bias in observational studies. The propensity score denotes the conditional probability of an individual to receive a certain treatment. A propensity score is generated for each patient based on all the confounding factors using a logistic regression model. The key advantage of propensity score matching is that by using a linear combination of covariates for a single score, it balances treatment and control groups on a large number of covariates without losing a large number of observations.13 In our study, TBI patients on preinjury Ibuprofen therapy were matched to TBI patients not on Ibuprofen based on their propensity scores. We selected the matching variables based on the literature, which signify these variables as being influential on patient outcomes. The 2 groups (Ibuprofen versus no-Ibuprofen) were then compared for differences in outcomes. The primary outcome measure was progression on RHCT. The secondary outcome measure was need for neurosurgical intervention. We defined progression on repeat head CT as the development of a new ICH or increase in size of the previous ICH. Neurosurgical intervention was defined as craniotomy or craniectomy. A subanalysis of the 2 groups was also performed for patients who did not receive platelet transfusion during their hospital stay. Data are reported as mean 6 standard deviation for continuous descriptive variables, median [range] for ordinal descriptive variables, and as proportions for categorical variables. We performed Mann–Whitney U and Student t test to explore for differences in the 2 groups for continuous variables. We used chi-square test to identify differences in outcomes between the 2 groups for categorical variables. For our study, we considered P value of less than .05 as statistically significant. All statistical analyses were performed using Statistical Package for Social Sciences Version 21 (IBM, Inc, Armonk, NY).
Methods After the approval of the Institutional Review Board at the University of Arizona, College of Medicine, we performed a 2-year (2011 to 2012) retrospective analysis of a prospectively maintained database of all TBI patients presenting to our Level 1 trauma center. Patients with intracranial hemorrhage (ICH) on initial head computed tomography (CT) and a repeat head CT scan who were on preinjury Ibuprofen therapy were included. Transferred patients, patients with unknown records, patients requiring an emergent neurosurgical intervention, and patients on preinjury antiplatelet therapy (Aspirin, Clopidogrel), anticoagulant therapy (Warfarin), and combination therapy were excluded from our study. We also excluded patients on NSAIDs other than Ibuprofen. We recorded the following data points: demographic data including age and sex, mechanism of injury, vital parameters on presentation, admission Glasgow Coma Scale (GCS) score, neurologic examination on presentation, medication history, platelet count and platelet transfusion, findings of the initial and repeat head computed tomography (RHCT) scan, neurosurgical intervention, hospital and intensive care unit (ICU) length of stay, and in-hospital mortality. Injury severity score (ISS) and head-abbreviated injury scale (h-AIS) score were extracted from trauma registry. The initial head CT scan obtained on presentation and RHCT obtained 6 hours after initial head CT scan were reviewed by the attending radiologist and reconfirmed by a single investigator for type and size of ICH (subdural, epidural, subarachnoid, intraparenchymal and intraventricular hemorrhage), and for type of skull fracture (displaced and nondisplaced). Neurologic examination was performed every hour to assess for clinical deterioration. We defined abnormal neurologic examination as altered mental status, focal neurologic deficits, or an abnormal pupillary examination. Any change in neurologic examination was recorded and a repeat head CT scan was performed for the patients who had a decline in neurologic examination. Patients on preinjury Ibuprofen (Ibuprofen group) were matched using propensity score matching to patients not on
Results A total of 2,399 TBI patients were identified, of which 1,082 [Ibuprofen 85, no-Ibuprofen 997] patients with ICH on initial head CT scan were reviewed (Fig. 1). After propensity score matching, 195 patients [Ibuprofen 65, noIbuprofen 130] were included. The mean age was 63.5 6 20.1 years, 69% were male, median GCS score was 14 [3 to 15], and median h-AIS was 3 [1 to 5]. There was no difference in patient demographics and injury severity between the 2 groups. Table 1 demonstrates the comparative demographics between the 2 groups of patients (Ibuprofen vs no-Ibuprofen).
B. Zangbar et al.
Pre-injury ibuprofen in TBI patients
3
Traumatic Brain Injury N=2399
Excluded N=1317
Total TBI Patients Included N = 1082 On Pre-injury Ibuprofen N = 85
Not on Pre-injury Ibuprofen N = 997 PROPENSITY SCORE MATCHING (1:2) Controlling for: Age, GCS, Head AIS, ISS, INR, Neuro-exam No-Ibuprofen N = 130 Matched Pairs
Ibuprofen N = 65 Matched Pairs
Figure 1
Details of the study population.
The mean platelet count was 257 6 96 (!103/mm3) and 18.9% (n 5 37) patients received platelet transfusion. Patients in Ibuprofen group were more likely to receive a platelet transfusion [Ibuprofen 35.4% (23) vs noIbuprofen 10.7% (14), P 5 .001]. There was no difference in admission platelet count of the patients who received
Table 1
platelet transfusion in both groups (202 6 95 vs 229 6 103, P 5 .42). Subdural hemorrhage (66.7%) followed by subarachnoid hemorrhage (51.3%) was the most common type of ICH found on initial head CT scan in both groups. The 2 groups were similar in presence and type of skull fractures and the
Patient characteristics
Variable
Ibuprofen (n 5 65)
No-ibuprofen (n 5 130)
P value
Age (years) Men Mechanism of injury Falls MVA GCS %8 9–12 R12 ISS Head AIS R3 Abnormal neuro-exam INR PT (seconds) PTT (seconds) Platelet count Platelet transfusion
63.6 6 20.3 42 (65%)
63.8 6 20.4 92 (71%)
.94 .47
36 (56%) 21 (32%) 14 [3–15] 12 (18.4%) 9 (13.8%) 44 (67.7%) 17 [9–45] 3 [1–5] 49 (75%) 13 (20%) 1.10 6 .3 15 6 2.4 29 6 6 250 6 91 23 (35.4%)
64 (49%) 38 (29%) 14 [3–15] 21 (16.1%) 14 (10.7%) 95 (73.1%) 19 [5–48] 3 [2–5] 107 (82%) 23 (18%) 1.05 6 .2 14.5 6 1.6 28 6 5 262 6 99 14 (10.7%)
.51 .78 .65 .75 .59 .52 .75 .90 .34 .84 .16 .08 .22 .41 .001
Data are expressed as number (percent), mean 6 standard deviation, or median [range]. GCS 5 Glasgow Coma Scale; Head-AIS 5 head-abbreviated injury scale; INR 5 International Normalized Ratio; ISS 5 injury severity score; MVA 5 motor vehicle accident; neuro-exam 5 neurologic physical examination; PT 5 prothrombin time; PTT 5 partial thromboplastin time.
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4 Table 2
Findings on initial head CT
Variable
Ibuprofen (n 5 65)
No-ibuprofen (n 5 130)
P value
Skull fracture Nondisplaced Displaced ICH SDH SDH size (mm) EDH EDH size (mm) SAH IVH IPH
21 (32%) 6 (28.5%) 15 (71.4%)
38 (29%) 16 (42.1%) 22 (57.8%)
.78 .68 .40
43 (66%) 5.7 6 6.4 5 (8%) 1 6 4.1 34 (52%) 5 (8%) 22 (34%)
87 (67%) 5.0 6 6.6 8 (6%) 1 6 3.2 66 (51%) 10 (8%) 44 (34%)
.91 .48 .76 .99 .95 .97 .98
Data are expressed as number (percent), mean 6 standard deviation. CT 5 computed tomography; EDH 5 epidural hematoma; ICH 5 intracranial hemorrhage; IPH 5 intraparenchymal hemorrhage; IVH 5 intraventricular hemorrhage; SAH 5 subarachnoid hemorrhage; SDH 5 subdural hematoma.
distribution and size of ICH. Table 2 highlights the findings on initial head CT scan in the study population. Overall, 22.0% (n 5 43) patients had progression on RHCT. There was no difference in progression on RHCT (P 5 .50) and having an RHCT because of neurologic decline (P 5 .33) between the 2 groups. The overall neurosurgical intervention rate was 18.9% (n 5 37). There was no difference in the need for neurosurgical intervention (P 5 .10) between the 2 groups. Intracranial pressure monitoring was performed in 9 patients. There was no difference in the requirement of intracranial pressure monitoring in both the groups (P 5 .27). On the subanalysis of the patients without a platelet transfusion (Ibuprofen 42, no-Ibuprofen 116), there was no difference in the rate of progression (9.5% vs 16.4%, P 5 .32) and need for neurosurgical intervention (14.3% vs 10.3%, P 5 .68) between the 2 groups. Table 3 highlights the findings of RHCT scan and neurosurgical intervention in the study population. We found no difference in hospital length of stay (P 5 .06) and ICU length of stay (P 5 .90) between patients on Ibuprofen therapy and patients not on Ibuprofen therapy. The overall mortality rate was 23.0% (n 5 45).
Table 3
Nonsurvived patients had severe TBI (head-AIS R 3: 64.4%, n 5 29) and overall severe injuries (ISS R 20: 60%, n 5 27). There was no difference in mortality rate (P 5 .58) between the 2 groups. Table 4 highlights the outcomes in the study population.
Comments The antiplatelet effect of Ibuprofen on clinical outcomes in patients with TBI has substantial importance with the increase in use of NSAIDs. In our matched cohort of patients, we found that there was no difference in progression on RHCT and neurosurgical intervention between the patients who were on Ibuprofen and the control group. Even after controlling for platelet transfusion, there was no difference in outcomes. Several studies have shown that NSAIDs have a complex interaction with both the coagulation system, through anti-inflammatory effects, as well as the platelet aggregation system, through reversible cyclooxygenase inhibition.3,14 Studies have linked the NSAID therapy to unfavorable clinical outcomes in patients with
RHCT scan findings and management
Variable
Ibuprofen (n 5 65)
No-ibuprofen (n 5 130)
OR
95% CI
P value
Progression on RHCT RHCT because of neurologic decline Neurosurgical intervention ICP monitoring
12 (18%) 1 (2%) 17 (26%) 5 (7.7%)
31 (24%) 0% 20 (16%) 4 (3%)
.7 d 1.6 .38
.2–1.9 d .5–4.6 .09–1.5
.50 .33 .10 .27
Patients with no platelet transfusion
(n 5 42)
(n 5 116)
Progression on RHCT RHCT because of neurologic decline Neurosurgical intervention ICP monitoring
4 1 6 4
19 (16.4%) 0% 12 (10.3%) 3 (2.6%)
.51 d 1.6 .25
.1–1.9 d .5–5.4 .05–1.2
.32 .26 .68 .08
(9.5%) (2.4%) (14.3%) (9.5%)
Data are expressed as number (percent). CI 5 confidence interval; ICP 5 intracranial pressure; OR 5 odds ratio; RHCT 5 repeat head computed tomography.
B. Zangbar et al. Table 4
Pre-injury ibuprofen in TBI patients
5
Length of stay and outcomes
Variable
Ibuprofen (n 5 65)
No-ibuprofen (n 5 130)
P value
Hospital LOS ICU LOS Vent days Mortality
11.0 6 10.8 4.7 6 6.1 2.7 6 5.1 13 (20%)
8.5 6 7.6 3.7 6 5.1 1.8 6 4.0 32 (24.6%)
.06 .22 .17 .58
Data are expressed as number (percent), mean 6 standard deviation. ICU 5 intensive care unit; LOS 5 length of stay.
cardiovascular disease.15 However, in trauma, there is no data assessing clinical impact of NSAIDs. Neal et al12 in a study has focused on the inhibitory effect of NSAIDs on trauma-induced coagulopathy. In our study, we assessed the antiplatelet effect of preinjury Ibuprofen on outcomes in a matched cohort of TBI patients. We also matched for INR to control for the possible inhibitory effect of Ibuprofen on trauma-induced coagulopathy on the outcomes. Studies have demonstrated higher rates of progression of initial ICH in patients on antiplatelet therapy.10,11,16,17 Fabbri et al demonstrated a 2-fold increase in risk of progression in patients on anti-platelet therapy, while Brewer et al showed that preinjury antiplatelet therapy is not a predictor for ICH in minor head trauma.10,18 However, these studies consisted of a heterogeneous patient population comprising of patients on Aspirin, Clopidogrel, and NSAIDs either excluded or combined. Considering different mechanism of action of these antiplatelet agents,14 a differential analysis is necessary to chart the guideline for effective management of these patients. In our institution, we have previously shown the effect of Clopidogrel and Aspirin, and even different doses of Aspirin separately in clinical progression of TBI.7,16,19 In this study, we report no difference in progression of ICH in a matched population of patients who were on Ibuprofen therapy only and patients who did not receive any antiplatelet medication. Studies have reported different rates for neurosurgical intervention in patients on anti-platelet therapy.16,20 However, patients on NSAIDs were either excluded in these studies or were low in numbers to be included in any analysis for outcomes separately. It has been shown that lowdose Aspirin therapy was not associated with clinical deterioration and need for neurosurgical intervention.19 In our study, there was no difference in need for neurosurgical intervention between the patients on Ibuprofen therapy and the matched control group. Also, there was no difference in the rate of intracranial pressure monitoring by external ventricular drain placement between the 2 groups. The current standard of managing TBI on antiplatelet therapy consists of an initial head CT scan and a follow-up RHCT. Kaups et al and Smith et al in separate studies on TBI patients have questioned the role of RHCT in the absence of a clinical indicator in this cohort of patients.21,22 With the national effort to reduce the use of CT scans, it is very important to identify the subset of patients on antiplatelet therapy who will benefit the most from a repeat
head CT. We believe that given the fact that patients on Ibuprofen have a similar likelihood of progression on RHCT and similar rate of neurosurgical intervention compared with patients not on Ibuprofen therapy, being on Ibuprofen therapy should not be considered as an independent reason for obtaining an RHCT. Neurologic examination in TBI patients who were not on antiplatelet medications has been shown to provide adequate information regarding clinical deterioration and need for RHCT scan.23,24 We suggest that routine RHCT may be replaced by neurologic examination in TBI patients on Ibuprofen. Studies have advocated transfusion of platelets in patients on antiplatelet therapy to arrest the progression of the initial ICH and reverse the inhibitory effects of the medication.25,26 However, the effect of platelet transfusion in TBI patients remains debatable.27,28 In a previous study, we have shown that progression of ICH was independent of platelet transfusion and transfusion of one pack of platelets did not change platelet function in a cohort of TBI patients.27 In this study, patients on Ibuprofen therapy were more likely to receive platelet transfusions. This may be because of presumed antiplatelet effect of the Ibuprofen, as there was no difference in admission platelet counts and laboratory values between the patients who received a platelet transfusion and the patients who did not. We did not have a protocol in place for platelet transfusion. We performed a subanalysis on patients without a platelet transfusion and found no difference in progression on RHCT and neurosurgical intervention between the 2 groups. We believe that assessing the actual platelet function in patients on Ibuprofen may provide us with an insight into the antiplatelet effects of this medication and the impact of platelet transfusion. Several studies have shown that preinjury antiplatelet therapy increases the risk of mortality in TBI patients.20,25 Contrastingly, Rozzelle et al showed that preinjury antiplatelets were not a risk factor for mortality.9 Although our study was not powered enough for mortality outcome, we also found no difference in hospital length of stay, ICU length of stay, and mortality between the 2 groups. The lack of difference in mortality in our study can also be attributed to the fact that we had a homogenous matched population of patients with no difference in progression of the initial injury or need for neurosurgical intervention. The findings of our study should be interpreted with consideration of its limitations. This was a single
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institutional study and we had a small number of patients on preinjury Ibuprofen therapy that could be enrolled. Although we only included the patients with complete medication history, patient’s medication history may be inaccurate because of the retrospective nature of the study. We also did not have the medication dosage and compliance. Although we performed propensity score matching to match the 2 groups, there may be other confounding factors that we could not control for. We did not perform point of care testing (ie Thromboelastography) to assess platelet function. There was no protocol in place for platelet transfusion and this was left to the discretion of the attending physician. The results of this study relate only to Ibuprofen use and may not be generalized to all NSAIDs. Despite these limitations, our study evaluates the effects of preinjury Ibuprofen therapy in patients with TBI and ICH and we conclude that patients on preinjury Ibuprofen does not have an increased risk for clinical and radiographic deterioration and should not receive a routine repeat head CT.
9. Rozzelle CJ, Wofford JL, Branch CL. Predictors of hospital mortality in older patients with subdural hematoma. J Am Geriatr Soc 1995;43: 240–4. 10. Fabbri A, Servadei F, Marchesini G, et al. Antiplatelet therapy and the outcome of subjects with intracranial injury: the Italian SIMEU study. Crit Care 2013;17:R53. 11. Fabbri A, Servadei F, Marchesini G, et al. Predicting intracranial lesions by antiplatelet agents in subjects with mild head injury. J Neurol Neurosurg Psychiatry 2010;81:1275–9. 12. Neal MD, Brown JB, Moore EE, et al. Prehospital use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of trauma-induced coagulopathy. Ann Surg; 2014. 13. Hemmila MR, Birkmeyer NJ, Arbabi S, et al. Introduction to propensity scores: a case study on the comparative effectiveness of laparoscopic vs open appendectomy. Arch Surg 2010;145:939–45. 14. Mackenzie IS, Coughtrie MW, MacDonald TM, et al. Antiplatelet drug interactions. J Intern Med 2010;268:516–29. 15. Amer M, Bead VR, Bathon J, et al. Use of nonsteroidal antiinflammatory drugs in patients with cardiovascular disease: a cautionary tale. Cardiol Rev 2010;18:204–12. 16. Joseph B, Sadoun M, Aziz H, et al. Repeat head computed tomography in anticoagulated traumatic brain injury patients: still warranted. Am Surg 2014;80:43–7. 17. Beynon C, Hertle DN, Unterberg AW, et al. Clinical review: traumatic brain injury in patients receiving antiplatelet medication. Crit Care 2012;16:228. 18. Brewer ES, Reznikov B, Liberman RF, et al. Incidence and predictors of intracranial hemorrhage after minor head trauma in patients taking anticoagulant and antiplatelet medication. J Trauma 2011;70: E1–5. 19. Joseph B, Aziz H, Pandit V, et al. Low-dose aspirin therapy is not a reason for repeating head computed tomographic scans in traumatic brain injury: a prospective study. J Surg Res 2014;186:287–91. 20. Ohm C, Mina A, Howells G, et al. Effects of antiplatelet agents on outcomes for elderly patients with traumatic intracranial hemorrhage. J Trauma 2005;58:518–22. 21. Kaups KL, Davis JW, Parks SN. Routinely repeated computed tomography after blunt head trauma: does it benefit patients? J Trauma 2004; 56:475–80; discussion, 480-1. 22. Smith JS, Chang EF, Rosenthal G, et al. The role of early follow-up computed tomography imaging in the management of traumatic brain injury patients with intracranial hemorrhage. J Trauma 2007;63: 75–82. 23. Aziz H, Rhee P, Pandit V, et al. Mild and moderate pediatric traumatic brain injury: replace routine repeat head computed tomography with neurologic examination. J Trauma Acute Care Surg 2013;75:550–4. 24. Joseph B, Aziz H, Pandit V, et al. A Three-year prospective study of repeat head computed tomography in patients with traumatic brain injury. J Am Coll Surg; 2014. 25. McMillian WD, Rogers FB. Management of prehospital antiplatelet and anticoagulant therapy in traumatic head injury: a review. J Trauma 2009;66:942–50. 26. Bachelani AM, Bautz JT, Sperry JL, et al. Assessment of platelet transfusion for reversal of aspirin after traumatic brain injury. Surgery 2011;150:836–43. 27. Joseph B, Pandit V, Sadoun M, et al. A prospective evaluation of platelet function in patients on antiplatelet therapy with traumatic intracranial hemorrhage. J Trauma Acute Care Surg 2013;75: 990–4. 28. Batchelor JS, Grayson A. A meta-analysis to determine the effect on survival of platelet transfusions in patients with either spontaneous or traumatic antiplatelet medication-associated intracranial haemorrhage. BMJ Open 2012;2:e000588.
Conclusions In a matched cohort of trauma patients, preinjury Ibuprofen use was not associated with progression of initial ICH and the need for neurosurgical intervention. Preinjury use of Ibuprofen as an independent variable should not warrant the need for a routine repeat head CT scan.
References 1. Wilcox CM, Shalek KA, Cotsonis G. Striking prevalence of over-thecounter nonsteroidal anti-inflammatory drug use in patients with upper gastrointestinal hemorrhage. Arch Intern Med 1994;154:42–6. 2. Cheng JC, Siegel LB, Katari B, et al. Nonsteroidal anti-inflammatory drugs and aspirin: a comparison of the antiplatelet effects. Am J Ther 1997;4:62–5. 3. Yokoyama H, Ito N, Soeda S, et al. Influence of non-steroidal antiinflammatory drugs on antiplatelet effect of aspirin. J Clin Pharm Ther 2013;38:12–5. 4. Gladding PA, Webster MW, Farrell HB, et al. The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers. Am J Cardiol 2008;101: 1060–3. 5. Goldenberg NA, Jacobson L, Manco-Johnson MJ. Brief communication: duration of platelet dysfunction after a 7-day course of Ibuprofen. Ann Intern Med 2005;142:506–9. 6. Zhou Y, Boudreau DM, Freedman AN. Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population. Pharmacoepidemiol Drug Saf 2014;23:43–50. 7. Joseph B, Pandit V, Aziz H, et al. Clinical outcomes in traumatic brain injury patients on preinjury clopidogrel: a prospective analysis. J Trauma Acute Care Surg 2014;76:817–20. 8. Joseph B, Aziz H, Zangbar B, et al. Acquired coagulopathy of traumatic brain injury defined by routine laboratory tests: which laboratory values matter? J Trauma Acute Care Surg 2014;76:121–5.
Clinical outcomes in patients on preinjury ibuprofen with traumatic brain injury Bardiya Zangbar, M.D., Viraj Pandit, M.D., Peter Rhee, M.D., Mazhar Khalil, M.D., Narong Kulvatunyou, M.D., Terence O’Keeffe, M.B., Ch.B., Andrew Tang, M.D., Lynn Gries, M.D., Donald J. Green, M.D., Randall S. Friese, M.D., Bellal Joseph, M.D.* Division of Trauma, Department of Surgery, University of Arizona, Tucson, AZ, USA
KEYWORDS: Ibuprofen; Motrin; Nonsteroidal antiinflammatory drugs; Traumatic brain injury; Repeat head computed tomography; Neurosurgical Intervention
Abstract BACKGROUND: The aim of our study was to evaluate the clinical outcomes in patients on preinjury Ibuprofen with traumatic brain injury. METHODS: We performed a 2-year analysis of all patients on prehospital Ibuprofen with traumatic brain injury and intracranial hemorrhage. Patients on preinjury Ibuprofen were matched using propensity score matching to patients not on Ibuprofen in a 1:2 ratio for age, Glasgow Coma Scale, headabbreviated injury scale, injury severity score, International Normalized Ratio, and neurologic examination. Outcome measures were progression on repeat head computed tomography (RHCT) and neurosurgical intervention. RESULTS: A total of 195 matched (Ibuprofen 65, no-Ibuprofen 130) patients were included. There was no difference in the progression on RHCT (Ibuprofen 18% vs no-Ibuprofen 24%; P 5 .50). The neurosurgical intervention rate was 18.9% (n 5 37). There was no difference for need for neurosurgical intervention (26% vs 16%; P 5 .10) between the 2 groups. CONCLUSIONS: In a matched cohort of trauma patients, preinjury Ibuprofen use was not associated with progression of initial intracranial hemorrhage and the need for neurosurgical intervention. Preinjury use of Ibuprofen as an independent variable should not warrant the need for a routine RHCT scan. Published by Elsevier Inc.
Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute one of the most widely used class of drugs, with more than 70 million prescriptions and more than 30 billion over-
There were no relevant financial relationships or any sources of support in the form of grants, equipment, or drugs. Oral presentation at the 66th Annual Southwestern Surgical Congress, April 13–16, 2014, Scottsdale, Arizona. * Corresponding author. Tel.: 11-520-626-5056; fax: 11-520-6265016. E-mail address: [email protected] Manuscript received May 1, 2014; revised manuscript May 11, 2014
0002-9610/$ - see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.amjsurg.2014.05.027
the-counter tablets sold annually in the United States.1 Many people take Ibuprofen or other NSAIDs for rheumatic disorders, headache, musculoskeletal problem, and pain control. The antiplatelet effect of nonsalicylate NSAIDs such as Ibuprofen as a reversible cyclooxygenase inhibitor has been widely assessed in both in vitro and in vivo studies.2–4 Based on these studies, they are often withdrawn 7 or more days before surgery to avoid potential bleeding complications.5 With the increase in trends of medical treatment by NSAIDs among US population,6 a greater proportion of the traumatic brain injury (TBI) patients are visiting trauma
2
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centers with a positive medical history of NSAIDs. However, studies focusing on TBI either exclude the patients on NSAIDs or combine them with all other preinjury medications with antiplatelet effect in a single group and evaluate them as a single variable.7–11 A recent study suggests that preinjury NSAID therapy reduces trauma-induced coagulopathy.12 However, despite the antiplatelet effect of these drugs, there is a paucity of literature studying this effect on the clinical outcomes of the patients with TBI on preinjury NSAID therapy. The aim of our study was to evaluate the effect of preinjury Ibuprofen on outcomes (progression and neurosurgical intervention) in patients with TBI.
Ibuprofen (no-Ibuprofen group) in a 1:2 ratio for age, GCS, systolic blood pressure, heart rate, h-AIS score, ISS, neurologic examination, INR, type and size of the ICH, and skull fracture. Propensity matching is an analog to the process of randomization of a clinical trial that is commonly used for dealing with selection bias in observational studies. The propensity score denotes the conditional probability of an individual to receive a certain treatment. A propensity score is generated for each patient based on all the confounding factors using a logistic regression model. The key advantage of propensity score matching is that by using a linear combination of covariates for a single score, it balances treatment and control groups on a large number of covariates without losing a large number of observations.13 In our study, TBI patients on preinjury Ibuprofen therapy were matched to TBI patients not on Ibuprofen based on their propensity scores. We selected the matching variables based on the literature, which signify these variables as being influential on patient outcomes. The 2 groups (Ibuprofen versus no-Ibuprofen) were then compared for differences in outcomes. The primary outcome measure was progression on RHCT. The secondary outcome measure was need for neurosurgical intervention. We defined progression on repeat head CT as the development of a new ICH or increase in size of the previous ICH. Neurosurgical intervention was defined as craniotomy or craniectomy. A subanalysis of the 2 groups was also performed for patients who did not receive platelet transfusion during their hospital stay. Data are reported as mean 6 standard deviation for continuous descriptive variables, median [range] for ordinal descriptive variables, and as proportions for categorical variables. We performed Mann–Whitney U and Student t test to explore for differences in the 2 groups for continuous variables. We used chi-square test to identify differences in outcomes between the 2 groups for categorical variables. For our study, we considered P value of less than .05 as statistically significant. All statistical analyses were performed using Statistical Package for Social Sciences Version 21 (IBM, Inc, Armonk, NY).
Methods After the approval of the Institutional Review Board at the University of Arizona, College of Medicine, we performed a 2-year (2011 to 2012) retrospective analysis of a prospectively maintained database of all TBI patients presenting to our Level 1 trauma center. Patients with intracranial hemorrhage (ICH) on initial head computed tomography (CT) and a repeat head CT scan who were on preinjury Ibuprofen therapy were included. Transferred patients, patients with unknown records, patients requiring an emergent neurosurgical intervention, and patients on preinjury antiplatelet therapy (Aspirin, Clopidogrel), anticoagulant therapy (Warfarin), and combination therapy were excluded from our study. We also excluded patients on NSAIDs other than Ibuprofen. We recorded the following data points: demographic data including age and sex, mechanism of injury, vital parameters on presentation, admission Glasgow Coma Scale (GCS) score, neurologic examination on presentation, medication history, platelet count and platelet transfusion, findings of the initial and repeat head computed tomography (RHCT) scan, neurosurgical intervention, hospital and intensive care unit (ICU) length of stay, and in-hospital mortality. Injury severity score (ISS) and head-abbreviated injury scale (h-AIS) score were extracted from trauma registry. The initial head CT scan obtained on presentation and RHCT obtained 6 hours after initial head CT scan were reviewed by the attending radiologist and reconfirmed by a single investigator for type and size of ICH (subdural, epidural, subarachnoid, intraparenchymal and intraventricular hemorrhage), and for type of skull fracture (displaced and nondisplaced). Neurologic examination was performed every hour to assess for clinical deterioration. We defined abnormal neurologic examination as altered mental status, focal neurologic deficits, or an abnormal pupillary examination. Any change in neurologic examination was recorded and a repeat head CT scan was performed for the patients who had a decline in neurologic examination. Patients on preinjury Ibuprofen (Ibuprofen group) were matched using propensity score matching to patients not on
Results A total of 2,399 TBI patients were identified, of which 1,082 [Ibuprofen 85, no-Ibuprofen 997] patients with ICH on initial head CT scan were reviewed (Fig. 1). After propensity score matching, 195 patients [Ibuprofen 65, noIbuprofen 130] were included. The mean age was 63.5 6 20.1 years, 69% were male, median GCS score was 14 [3 to 15], and median h-AIS was 3 [1 to 5]. There was no difference in patient demographics and injury severity between the 2 groups. Table 1 demonstrates the comparative demographics between the 2 groups of patients (Ibuprofen vs no-Ibuprofen).
B. Zangbar et al.
Pre-injury ibuprofen in TBI patients
3
Traumatic Brain Injury N=2399
Excluded N=1317
Total TBI Patients Included N = 1082 On Pre-injury Ibuprofen N = 85
Not on Pre-injury Ibuprofen N = 997 PROPENSITY SCORE MATCHING (1:2) Controlling for: Age, GCS, Head AIS, ISS, INR, Neuro-exam No-Ibuprofen N = 130 Matched Pairs
Ibuprofen N = 65 Matched Pairs
Figure 1
Details of the study population.
The mean platelet count was 257 6 96 (!103/mm3) and 18.9% (n 5 37) patients received platelet transfusion. Patients in Ibuprofen group were more likely to receive a platelet transfusion [Ibuprofen 35.4% (23) vs noIbuprofen 10.7% (14), P 5 .001]. There was no difference in admission platelet count of the patients who received
Table 1
platelet transfusion in both groups (202 6 95 vs 229 6 103, P 5 .42). Subdural hemorrhage (66.7%) followed by subarachnoid hemorrhage (51.3%) was the most common type of ICH found on initial head CT scan in both groups. The 2 groups were similar in presence and type of skull fractures and the
Patient characteristics
Variable
Ibuprofen (n 5 65)
No-ibuprofen (n 5 130)
P value
Age (years) Men Mechanism of injury Falls MVA GCS %8 9–12 R12 ISS Head AIS R3 Abnormal neuro-exam INR PT (seconds) PTT (seconds) Platelet count Platelet transfusion
63.6 6 20.3 42 (65%)
63.8 6 20.4 92 (71%)
.94 .47
36 (56%) 21 (32%) 14 [3–15] 12 (18.4%) 9 (13.8%) 44 (67.7%) 17 [9–45] 3 [1–5] 49 (75%) 13 (20%) 1.10 6 .3 15 6 2.4 29 6 6 250 6 91 23 (35.4%)
64 (49%) 38 (29%) 14 [3–15] 21 (16.1%) 14 (10.7%) 95 (73.1%) 19 [5–48] 3 [2–5] 107 (82%) 23 (18%) 1.05 6 .2 14.5 6 1.6 28 6 5 262 6 99 14 (10.7%)
.51 .78 .65 .75 .59 .52 .75 .90 .34 .84 .16 .08 .22 .41 .001
Data are expressed as number (percent), mean 6 standard deviation, or median [range]. GCS 5 Glasgow Coma Scale; Head-AIS 5 head-abbreviated injury scale; INR 5 International Normalized Ratio; ISS 5 injury severity score; MVA 5 motor vehicle accident; neuro-exam 5 neurologic physical examination; PT 5 prothrombin time; PTT 5 partial thromboplastin time.
The American Journal of Surgery, Vol -, No -, - 2014
4 Table 2
Findings on initial head CT
Variable
Ibuprofen (n 5 65)
No-ibuprofen (n 5 130)
P value
Skull fracture Nondisplaced Displaced ICH SDH SDH size (mm) EDH EDH size (mm) SAH IVH IPH
21 (32%) 6 (28.5%) 15 (71.4%)
38 (29%) 16 (42.1%) 22 (57.8%)
.78 .68 .40
43 (66%) 5.7 6 6.4 5 (8%) 1 6 4.1 34 (52%) 5 (8%) 22 (34%)
87 (67%) 5.0 6 6.6 8 (6%) 1 6 3.2 66 (51%) 10 (8%) 44 (34%)
.91 .48 .76 .99 .95 .97 .98
Data are expressed as number (percent), mean 6 standard deviation. CT 5 computed tomography; EDH 5 epidural hematoma; ICH 5 intracranial hemorrhage; IPH 5 intraparenchymal hemorrhage; IVH 5 intraventricular hemorrhage; SAH 5 subarachnoid hemorrhage; SDH 5 subdural hematoma.
distribution and size of ICH. Table 2 highlights the findings on initial head CT scan in the study population. Overall, 22.0% (n 5 43) patients had progression on RHCT. There was no difference in progression on RHCT (P 5 .50) and having an RHCT because of neurologic decline (P 5 .33) between the 2 groups. The overall neurosurgical intervention rate was 18.9% (n 5 37). There was no difference in the need for neurosurgical intervention (P 5 .10) between the 2 groups. Intracranial pressure monitoring was performed in 9 patients. There was no difference in the requirement of intracranial pressure monitoring in both the groups (P 5 .27). On the subanalysis of the patients without a platelet transfusion (Ibuprofen 42, no-Ibuprofen 116), there was no difference in the rate of progression (9.5% vs 16.4%, P 5 .32) and need for neurosurgical intervention (14.3% vs 10.3%, P 5 .68) between the 2 groups. Table 3 highlights the findings of RHCT scan and neurosurgical intervention in the study population. We found no difference in hospital length of stay (P 5 .06) and ICU length of stay (P 5 .90) between patients on Ibuprofen therapy and patients not on Ibuprofen therapy. The overall mortality rate was 23.0% (n 5 45).
Table 3
Nonsurvived patients had severe TBI (head-AIS R 3: 64.4%, n 5 29) and overall severe injuries (ISS R 20: 60%, n 5 27). There was no difference in mortality rate (P 5 .58) between the 2 groups. Table 4 highlights the outcomes in the study population.
Comments The antiplatelet effect of Ibuprofen on clinical outcomes in patients with TBI has substantial importance with the increase in use of NSAIDs. In our matched cohort of patients, we found that there was no difference in progression on RHCT and neurosurgical intervention between the patients who were on Ibuprofen and the control group. Even after controlling for platelet transfusion, there was no difference in outcomes. Several studies have shown that NSAIDs have a complex interaction with both the coagulation system, through anti-inflammatory effects, as well as the platelet aggregation system, through reversible cyclooxygenase inhibition.3,14 Studies have linked the NSAID therapy to unfavorable clinical outcomes in patients with
RHCT scan findings and management
Variable
Ibuprofen (n 5 65)
No-ibuprofen (n 5 130)
OR
95% CI
P value
Progression on RHCT RHCT because of neurologic decline Neurosurgical intervention ICP monitoring
12 (18%) 1 (2%) 17 (26%) 5 (7.7%)
31 (24%) 0% 20 (16%) 4 (3%)
.7 d 1.6 .38
.2–1.9 d .5–4.6 .09–1.5
.50 .33 .10 .27
Patients with no platelet transfusion
(n 5 42)
(n 5 116)
Progression on RHCT RHCT because of neurologic decline Neurosurgical intervention ICP monitoring
4 1 6 4
19 (16.4%) 0% 12 (10.3%) 3 (2.6%)
.51 d 1.6 .25
.1–1.9 d .5–5.4 .05–1.2
.32 .26 .68 .08
(9.5%) (2.4%) (14.3%) (9.5%)
Data are expressed as number (percent). CI 5 confidence interval; ICP 5 intracranial pressure; OR 5 odds ratio; RHCT 5 repeat head computed tomography.
B. Zangbar et al. Table 4
Pre-injury ibuprofen in TBI patients
5
Length of stay and outcomes
Variable
Ibuprofen (n 5 65)
No-ibuprofen (n 5 130)
P value
Hospital LOS ICU LOS Vent days Mortality
11.0 6 10.8 4.7 6 6.1 2.7 6 5.1 13 (20%)
8.5 6 7.6 3.7 6 5.1 1.8 6 4.0 32 (24.6%)
.06 .22 .17 .58
Data are expressed as number (percent), mean 6 standard deviation. ICU 5 intensive care unit; LOS 5 length of stay.
cardiovascular disease.15 However, in trauma, there is no data assessing clinical impact of NSAIDs. Neal et al12 in a study has focused on the inhibitory effect of NSAIDs on trauma-induced coagulopathy. In our study, we assessed the antiplatelet effect of preinjury Ibuprofen on outcomes in a matched cohort of TBI patients. We also matched for INR to control for the possible inhibitory effect of Ibuprofen on trauma-induced coagulopathy on the outcomes. Studies have demonstrated higher rates of progression of initial ICH in patients on antiplatelet therapy.10,11,16,17 Fabbri et al demonstrated a 2-fold increase in risk of progression in patients on anti-platelet therapy, while Brewer et al showed that preinjury antiplatelet therapy is not a predictor for ICH in minor head trauma.10,18 However, these studies consisted of a heterogeneous patient population comprising of patients on Aspirin, Clopidogrel, and NSAIDs either excluded or combined. Considering different mechanism of action of these antiplatelet agents,14 a differential analysis is necessary to chart the guideline for effective management of these patients. In our institution, we have previously shown the effect of Clopidogrel and Aspirin, and even different doses of Aspirin separately in clinical progression of TBI.7,16,19 In this study, we report no difference in progression of ICH in a matched population of patients who were on Ibuprofen therapy only and patients who did not receive any antiplatelet medication. Studies have reported different rates for neurosurgical intervention in patients on anti-platelet therapy.16,20 However, patients on NSAIDs were either excluded in these studies or were low in numbers to be included in any analysis for outcomes separately. It has been shown that lowdose Aspirin therapy was not associated with clinical deterioration and need for neurosurgical intervention.19 In our study, there was no difference in need for neurosurgical intervention between the patients on Ibuprofen therapy and the matched control group. Also, there was no difference in the rate of intracranial pressure monitoring by external ventricular drain placement between the 2 groups. The current standard of managing TBI on antiplatelet therapy consists of an initial head CT scan and a follow-up RHCT. Kaups et al and Smith et al in separate studies on TBI patients have questioned the role of RHCT in the absence of a clinical indicator in this cohort of patients.21,22 With the national effort to reduce the use of CT scans, it is very important to identify the subset of patients on antiplatelet therapy who will benefit the most from a repeat
head CT. We believe that given the fact that patients on Ibuprofen have a similar likelihood of progression on RHCT and similar rate of neurosurgical intervention compared with patients not on Ibuprofen therapy, being on Ibuprofen therapy should not be considered as an independent reason for obtaining an RHCT. Neurologic examination in TBI patients who were not on antiplatelet medications has been shown to provide adequate information regarding clinical deterioration and need for RHCT scan.23,24 We suggest that routine RHCT may be replaced by neurologic examination in TBI patients on Ibuprofen. Studies have advocated transfusion of platelets in patients on antiplatelet therapy to arrest the progression of the initial ICH and reverse the inhibitory effects of the medication.25,26 However, the effect of platelet transfusion in TBI patients remains debatable.27,28 In a previous study, we have shown that progression of ICH was independent of platelet transfusion and transfusion of one pack of platelets did not change platelet function in a cohort of TBI patients.27 In this study, patients on Ibuprofen therapy were more likely to receive platelet transfusions. This may be because of presumed antiplatelet effect of the Ibuprofen, as there was no difference in admission platelet counts and laboratory values between the patients who received a platelet transfusion and the patients who did not. We did not have a protocol in place for platelet transfusion. We performed a subanalysis on patients without a platelet transfusion and found no difference in progression on RHCT and neurosurgical intervention between the 2 groups. We believe that assessing the actual platelet function in patients on Ibuprofen may provide us with an insight into the antiplatelet effects of this medication and the impact of platelet transfusion. Several studies have shown that preinjury antiplatelet therapy increases the risk of mortality in TBI patients.20,25 Contrastingly, Rozzelle et al showed that preinjury antiplatelets were not a risk factor for mortality.9 Although our study was not powered enough for mortality outcome, we also found no difference in hospital length of stay, ICU length of stay, and mortality between the 2 groups. The lack of difference in mortality in our study can also be attributed to the fact that we had a homogenous matched population of patients with no difference in progression of the initial injury or need for neurosurgical intervention. The findings of our study should be interpreted with consideration of its limitations. This was a single
6
The American Journal of Surgery, Vol -, No -, - 2014
institutional study and we had a small number of patients on preinjury Ibuprofen therapy that could be enrolled. Although we only included the patients with complete medication history, patient’s medication history may be inaccurate because of the retrospective nature of the study. We also did not have the medication dosage and compliance. Although we performed propensity score matching to match the 2 groups, there may be other confounding factors that we could not control for. We did not perform point of care testing (ie Thromboelastography) to assess platelet function. There was no protocol in place for platelet transfusion and this was left to the discretion of the attending physician. The results of this study relate only to Ibuprofen use and may not be generalized to all NSAIDs. Despite these limitations, our study evaluates the effects of preinjury Ibuprofen therapy in patients with TBI and ICH and we conclude that patients on preinjury Ibuprofen does not have an increased risk for clinical and radiographic deterioration and should not receive a routine repeat head CT.
9. Rozzelle CJ, Wofford JL, Branch CL. Predictors of hospital mortality in older patients with subdural hematoma. J Am Geriatr Soc 1995;43: 240–4. 10. Fabbri A, Servadei F, Marchesini G, et al. Antiplatelet therapy and the outcome of subjects with intracranial injury: the Italian SIMEU study. Crit Care 2013;17:R53. 11. Fabbri A, Servadei F, Marchesini G, et al. Predicting intracranial lesions by antiplatelet agents in subjects with mild head injury. J Neurol Neurosurg Psychiatry 2010;81:1275–9. 12. Neal MD, Brown JB, Moore EE, et al. Prehospital use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of trauma-induced coagulopathy. Ann Surg; 2014. 13. Hemmila MR, Birkmeyer NJ, Arbabi S, et al. Introduction to propensity scores: a case study on the comparative effectiveness of laparoscopic vs open appendectomy. Arch Surg 2010;145:939–45. 14. Mackenzie IS, Coughtrie MW, MacDonald TM, et al. Antiplatelet drug interactions. J Intern Med 2010;268:516–29. 15. Amer M, Bead VR, Bathon J, et al. Use of nonsteroidal antiinflammatory drugs in patients with cardiovascular disease: a cautionary tale. Cardiol Rev 2010;18:204–12. 16. Joseph B, Sadoun M, Aziz H, et al. Repeat head computed tomography in anticoagulated traumatic brain injury patients: still warranted. Am Surg 2014;80:43–7. 17. Beynon C, Hertle DN, Unterberg AW, et al. Clinical review: traumatic brain injury in patients receiving antiplatelet medication. Crit Care 2012;16:228. 18. Brewer ES, Reznikov B, Liberman RF, et al. Incidence and predictors of intracranial hemorrhage after minor head trauma in patients taking anticoagulant and antiplatelet medication. J Trauma 2011;70: E1–5. 19. Joseph B, Aziz H, Pandit V, et al. Low-dose aspirin therapy is not a reason for repeating head computed tomographic scans in traumatic brain injury: a prospective study. J Surg Res 2014;186:287–91. 20. Ohm C, Mina A, Howells G, et al. Effects of antiplatelet agents on outcomes for elderly patients with traumatic intracranial hemorrhage. J Trauma 2005;58:518–22. 21. Kaups KL, Davis JW, Parks SN. Routinely repeated computed tomography after blunt head trauma: does it benefit patients? J Trauma 2004; 56:475–80; discussion, 480-1. 22. Smith JS, Chang EF, Rosenthal G, et al. The role of early follow-up computed tomography imaging in the management of traumatic brain injury patients with intracranial hemorrhage. J Trauma 2007;63: 75–82. 23. Aziz H, Rhee P, Pandit V, et al. Mild and moderate pediatric traumatic brain injury: replace routine repeat head computed tomography with neurologic examination. J Trauma Acute Care Surg 2013;75:550–4. 24. Joseph B, Aziz H, Pandit V, et al. A Three-year prospective study of repeat head computed tomography in patients with traumatic brain injury. J Am Coll Surg; 2014. 25. McMillian WD, Rogers FB. Management of prehospital antiplatelet and anticoagulant therapy in traumatic head injury: a review. J Trauma 2009;66:942–50. 26. Bachelani AM, Bautz JT, Sperry JL, et al. Assessment of platelet transfusion for reversal of aspirin after traumatic brain injury. Surgery 2011;150:836–43. 27. Joseph B, Pandit V, Sadoun M, et al. A prospective evaluation of platelet function in patients on antiplatelet therapy with traumatic intracranial hemorrhage. J Trauma Acute Care Surg 2013;75: 990–4. 28. Batchelor JS, Grayson A. A meta-analysis to determine the effect on survival of platelet transfusions in patients with either spontaneous or traumatic antiplatelet medication-associated intracranial haemorrhage. BMJ Open 2012;2:e000588.
Conclusions In a matched cohort of trauma patients, preinjury Ibuprofen use was not associated with progression of initial ICH and the need for neurosurgical intervention. Preinjury use of Ibuprofen as an independent variable should not warrant the need for a routine repeat head CT scan.
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