EDITORIAL
Do We Need New Guidelines for Interventional Pain Procedures in Patients on Anticoagulants? Honorio T. Benzon, MD* and Marc A. Huntoon, MD†
n this issue of Regional Anesthesia and Pain Medicine, Giberson et al1 and Buvanendran and Young2 report the occurrence of spinal epidural hematomas in patients whose only apparent risk factor for the hematoma was their use of aspirin. These 3 cases are notable because the current guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA) for the placement of epidural and spinal catheters do not recommend cessation of these antiplatelet agents for epidural procedures; nor do the guidelines differentiate between the often disparate procedures for interventional pain and those performed for perioperative anesthesia/analgesia.3 There are several reasons why the issue of antiplatelet agents and possibly other anticoagulants for some chronic pain procedures (eg, percutaneous spinal cord stimulation lead placement) may need to be rethought. First, the procedure for spinal cord stimulation lead placement requires the use of very large bore 14-gauge needles with a long ramped bevel to enhance directional control. These needles are placed at shallow angles into the interlaminar opening and, quite commonly, there is a need to place 2 or more needles and sometimes even to replace the needles. This is done in the presence of fibrous adhesions, plica mediana dorsalis, scar, or spinal canal stenosis/anatomical narrowing that prevents passage of the lead in the anatomical midline from the point of epidural space entry. Second, the leads are stiff, styletted cylindrical objects with multiple electrode contacts (up to 16), and may require repeated manipulation to achieve optimal locations for stimulation paresthesias that are analgesic. As noted, this process can entail multiple changes of stylets, repeated retraction, and steering of the leads into different areas of the epidural space.2 When leads are retracted, as noted by Giberson and colleagues,1 there may be a risk for “snagging” the edge of the lead, causing a sharp edge. Third, it is not rare for the lead to move laterally within the epidural space or even to enter the anterior epidural space despite apparent midline placement during fluoroscopy in the anteroposterior plane. To some extent, this risk can be reduced by alternating biplanar imaging, particularly using the lateral view. It may be that the lateral or anterior areas of the epidural space, where veins may be more prevalent, are at greater risk for vascular trespass. In some cases, however, the targeted area may be the lateral “gutter” of the epidural space. Fourth, technology is changing as quickly as the number of new pharmaceutical agents for anticoagulation. There are other types of percutaneous leads that are more paddle-shaped being placed through introducers as well as ongoing trials of novel dorsal root ganglion leads,4 which are designed to intentionally exit the neural foramen with unknown cumulative risks of bleeding/vascular trespass. Finally, the safety of placing chronic long-term stimulation devices in patients who will need to resume anticoagulation remains largely uncertain. Worries about lead migration causing a rebleed remain. In the 2 cases described by Giberson and colleagues,1 the hematomas seemed to be related to the removal of the spinal cord stimulator (SCS) leads. One patient took an aspirin-containing medication the morning the leads were pulled out. It is possible that this unique patient developed a spinal hematoma the first time he complained of back pain and transient paraplegia the day after the electrodes were placed. Unfortunately, no imaging was performed in the emergency department to confirm or rule out this possibility. The other patient stopped aspirin and “other nonsteroidal anti-inflammatory drugs” a week before the trial. The leads were removed 4 days later, or 11 days after the antiplatelet medications were stopped. Bleeding after removal of catheters is known; the reasons include trauma to vascular structures during manipulation and/or dislodgement of a clot or in the setting of full anticoagulation.5–7 In fact, Vandermeulen et al8 noted that almost half of the cases of reported spinal hematoma occurred immediately after removal of the catheter, leading to the ASRA recommendations that the same guidelines should apply to both placement and removal
I
From the *Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL; and †Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN. Accepted for publication October 21, 2013. Address correspondence to: Marc A. Huntoon, MD, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN (e‐mail: [email protected]). The authors declare no conflict of interest. Copyright © 2014 by American Society of Regional Anesthesia and Pain Medicine ISSN: 1098-7339 DOI: 10.1097/AAP.0000000000000040
Regional Anesthesia and Pain Medicine • Volume 39, Number 1, January-February 2014
1
Copyright © 2013 American Society of Regional Anesthesia and Pain Medicine. Unauthorized reproduction of this article is prohibited.
Regional Anesthesia and Pain Medicine • Volume 39, Number 1, January-February 2014
Editorial
TABLE 1. Cases of Spinal Hematoma After Interventional Pain Procedures Intervention; Patient Profile
Report Franzini et al
Kloss et al11
Smith et al12
9
Medications
SCS placement; NSAIDs, 69-year-old man antiepileptics, antidepressants, opiates SCS placement; Not described 50-year-old man
Two cases, SCS placement; 44-year-old man and 66-year-old woman
Takawira et al13 SCS placement; 52-year-old man Williams et al14 CESI; 63-year-old man Ghaly15
CESI; 57-year-old man
Reitman and Watters,16
CESI; 62-year-old woman
Ain and Vance17
LESI; 85-year-old woman, renal insufficiency
Xu et al18
LESI; 78-year-old woman
Timing of Symptoms
Treatment and Outcome
Immediately after SCS
Laminectomy performed after MRI; recovery
Interval between SCS placement and symptoms not described
Laminectomy, partial recovery
Comments Coagulation studies normal
Article is a “Clinical Image” paper with minimal description of circumstance Neither patient on Symptoms on POD5 Laminectomy, no Coagulation antiplatelets in patient 1; recovery (T8 paraplegia) studies normal in or other immediately after in patient 1; full motor both patients anticoagulants procedure in recovery but with patient 2 numbness below T8 in patient 2 Not described Symptoms occurred No laminectomy, Repeat MRI 5 d later on third day of trial spontaneous recovery showed complete of sensory and motor resolution of hematoma functions Indomethacin and Within 2 h after Laminectomy, full INR, clotting time, allopurinol procedure recovery platelet count normal Diclofenac sodium, Within 30 min High-dose Coagulation studies amitriptyline of procedure methylprednisolone normal initially, laminectomy 10 h later; full recovery Fiorinal stopped Within 2 h Laminectomy 11 h after PT, PTT normal for 1 wk CESI; partial recovery complicated by CSF leak and meningitis, patient died Warfarin withheld 48 h after procedure Laminectomy 24–36 h Warfarin resumed 6 days, enoxaparin after symptoms + evening after ESI, withheld 24 h, dexamethasone for 3 d; enoxaparin INR 1.2 before ESI motor recovery, residual restarted 24 h later; numbness of left toes INR 1.2 next day Warfarin and aspirin Approximately Laminectomy within Warfarin restarted 8 h discontinued for 42 h after ESI few hours of symptoms; after ESI, enoxaparin 6 d, enoxaparin full recovery resumed 30 h later stopped for 24 h, INR normal
CESI indicates cervical epidural steroid injection; LESI, lumbar epidural steroid injection; epidural steroid injection; INR, international normalized ratio; MRI, magnetic resonance imaging; NSAIDs, nonsteroidal anti-inflammatory drugs; POD, postoperative day; PT, prothrombin time; PTT, partial thromboplastin time; SCS, spinal cord stimulator.
of epidural catheters.3 In the case reported by Buvanendran and Young,2 the patient began to experience symptoms the day after trial placement. She had continued aspirin (ASA), in accordance with the ASRA guidelines,3 but began to experience neurological signs before discharge after an overnight stay. A complete laboratory workup did not uncover other risk factors outside of the ASA.2 There are other reports of spinal hematomas associated with SCS placement or removal (Table 1).9–13 There are also case reports of spinal hematoma after epidural steroid injections in patients who were only on anti-inflammatory agents14,15 or aspirin,16 or despite the guidelines being followed (Table 1).17,18 Patients with chronic pain, in particular, may be on medications that can cause bleeding abnormalities. Although thrombocytopenia from carbamazepine is known, there are case reports of thrombocytopenia with oxcarbazepine.19 Although
2
the incidence of thrombocytopenia is lower after oxcarbazepine compared with carbamazepine (1.7% vs 2.9%), there is a significant negative correlation between the platelet count and the daily doses of both drugs.20 Valproate also causes thrombocytopenia, with the incidence around 18%.21 A significant negative correlation was also noted between valproate blood levels and platelet counts; female sex, patients older than 65 years, low baseline platelet counts, and dosages greater than 1000 mg/day were noted as risk factors.21,22 Thrombocytopenia after levetiracetam has also been reported.23 The tricyclic antidepressants seem not to cause bleeding but the selective serotonin reuptake inhibitors (SSRIs) have been associated with increased bleeding.24–28 The antiplatelet effect of SSRIs is related to its antagonism of the serotonin transporters or depletion of serotonin in the platelets, resulting in inhibition of serotonin-mediated platelet activation, or reduction in platelet counts.27,28 The degree of the antiplatelet effect of © 2014 American Society of Regional Anesthesia and Pain Medicine
Copyright © 2013 American Society of Regional Anesthesia and Pain Medicine. Unauthorized reproduction of this article is prohibited.
Regional Anesthesia and Pain Medicine • Volume 39, Number 1, January-February 2014
the SSRIs may be related to the drug’s degree of inhibition of serotonin reuptake.25,26 The absolute effect of SSRIs is moderate, about equivalent to low-dose ibuprofen.24 However, the combination of antiplatelet drugs increases the risk of bleeding.29 The anticoagulant effects of SSRIs and the other drugs used for pain management, although mild, are generally not known to clinicians. In fact, in the case reports of spinal hematoma after SCS placement, only the patients’ intake of “antiplatelets or other anticoagulants” was noted. The patients who developed spinal hematoma after epidural steroid injections were only on antiplatelet drugs (Table 1). Patients with back pain have spine abnormalities including spinal stenosis, with smaller capacity of their epidural spaces. The risks are magnified when patients take several medications including SSRIs, nonsteroidal anti-inflammatory drugs for acute exacerbation of radicular pain, and aspirin for cardiac or neurological reasons. The pain interventionalist may not be aware of these drug-induced changes and may proceed with their planned intervention despite the presence of these medications. This brings us back to the question posed by Giberson et al1 and Buvanendran and Young2 on developing separate ASRA guidelines for interventional pain procedures in patients on anticoagulants. Regional Anesthesia and Pain Medicine and ASRA have recommended that separate guidelines for pain be proposed, and a committee has been formed. The guidelines will have an international representation, with experts from the European Society of Regional Anesthesia and Pain Therapy and probably other societies participating in the formation of the guidelines. Although the guidelines may not be based on randomized studies or on large numbers of patients from pooled databases, it is hoped that they will provide reasonable recommendations and the evidentiary basis for such recommendations. The continuing safety of these procedures for our patients mandates that we take measured and reasonable actions on their behalf based on the best interpretation of existing literature. REFERENCES
Editorial
10. Santiago FM, Santiago J, Prieto M, et al. Dorsal epidural hematoma after implantation of a dorsal nerve stimulator (Spanish). Rev Esp Anestesiol Reanim. 2005;52:440–441. 11. Kloss BT, Sullivan AM, Rodriquez E. Epidural hematoma following spinal cord stimulator implant. Int J Emerg Med. 2010;3:483–484. 12. Smith CC, Lin JL, Shokat M, Dosanjh SS, Casthely D. A report of paraparesis following spinal cord stimulator trial, implantation and revision. Pain Physician. 2010;13:357–363. 13. Takawira N, Han RJ, Nguyen TQ, Gaines JD, Han TH. Spinal cord stimulator and epidural haematoma. Br J Anaesth. 2012;109:649–650. 14. Williams KN, Jackowski A, Evans PJD. Epidural haematoma requiring surgical decompression following repeated cervical epidural steroid injections for chronic pain. Pain. 1990;42:197–199. 15. Ghaly RF. Recovery after high-dose methylprednisolone and delayed evacuation. J Neurosurg Anesthesiol. 2001;4:323–328. 16. Reitman CA, Watters W. Subdural hematoma after cervical epidural steroid injection. Spine. 2002;27:E174–E176. 17. Ain RJ, Vance MB. Epidural hematoma after epidural steroid injection in a patient withholding enoxaparin per guidelines. Anesthesiology. 2005;102:701–703. 18. Xu RX, Bydon M, Gokaslan ZL, Wolinsky JP, Witham TF, Bydon A. Epidural steroid injection resulting epidural hematoma in a patient despite strict adherence to anticoagulation guidelines. J Neurosurg Spine. 2009;11:358–364. 19. Mahmoud J, Mathews M, Verna S, Basil B. Oxcarbazepine-induced thrombocytopenia. Psychosomatics. 2006;47:73–74. 20. Tutor-Crespo MJ, Hermida J, Tutor JC. Relation of blood platelet count during carbamazepine and oxcarbazepine treatment with daily dose, and serum concentrations of carbamazepine, carbamazepine-10,11-epoxide, and 10-hydroxycarbazepine. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007;151:91–94. 21. Nasreddine W, Beydoun A. Valproate-induced thrombocytopenia: a prospective monotherapy study. Epilepsia. 2008;49:438–445. 22. Conley EL, Coley KC, Pollock BG, Dapos SV, Maxwell R, Branch RA. Prevalence and risk of thrombocytopenia with valproic acid: experience at a psychiatric teaching hospital. Pharmacotherapy. 2001;21:1325–1330.
1. Giberson CE, Barbosa J, Brooks ES, et al. Epidural hematomas following removal of percutaneous spinal cord stimulator trial leads: two case reports. Reg Anesth Pain Med. 2014;39:73–77.
23. Oghlakian R, Nock C, Koubeissi M. A case of levetiracetam-induced thrombocytopenia. Epileptic Disord. 2010;12:335–337.
2. Buvanendran A, Young AC. Spinal epidural hematoma following spinal cord stimulator trial lead placement in a patient taking aspirin. Reg Anesth Pain Med. 2014;39:70–72.
24. de Abajo FJ, Rodriquez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population-based control study. BMJ. 1999;319:1106–1109.
3. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy. Reg Anesth Pain Med. 2010;35:64–101.
25. van Walraven C, Mamdani MM, Wells PS, Williams JI. Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ. 2001;323:655–658.
4. Deer TR, Grigsby E, Weiner RL, et al. A prospective study of dorsal root ganglion stimulation for the relief of chronic pain. Neuromodulation. 2013;16:67–72. 5. Janis KM. Epidural hematoma following postoperative epidural analgesia: a case report. Anesth Analg. 1972;51:689–692. 6. Helperin SW, Cohen DD. Hematoma following epidural anesthesia: report of a case. Anesthesiology. 1971;35:641–644. 7. Stevens DS. Epidural hematoma: was catheter removed during complete anticoagulation? Anesth Analg. 1992;75:863–864.
26. Meijer WEE, Heerdink ER, Nolen WA, Herings RMC, Leufkens HGM, Egberts ACG. Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants. Arch Intern Med. 2004;164:2367–2370. 27. Labos C, Dasgupta K, Nedjar H, Turecki G, Rahme E. Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. CMAJ. 2011;183:1835–1843.
8. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg. 1994;79:1165–1177.
28. Cochran KA, Cavallari LH, Shapiro NL, Bishop JR. Bleeding incidence with concomitant use of antidepressants and warfarin. Ther Drug Monit. 2011;33:433–438.
9. Franzini A, Ferroli P, Marras C, Broggi G. Huge epidural hematoma after surgery for spinal cord stimulation. Acta Neurochir (Wien). 2005;147:565–567.
29. Benzon HT, Wong H, Siddiqui T, Ondra S. Caution in performing epidural injections in patients on several antiplatelet drugs. Anesthesiology. 1999;91:1558–1559.
© 2014 American Society of Regional Anesthesia and Pain Medicine
3
Copyright © 2013 American Society of Regional Anesthesia and Pain Medicine. Unauthorized reproduction of this article is prohibited.
Do We Need New Guidelines for Interventional Pain Procedures in Patients on Anticoagulants? Honorio T. Benzon, MD* and Marc A. Huntoon, MD†
n this issue of Regional Anesthesia and Pain Medicine, Giberson et al1 and Buvanendran and Young2 report the occurrence of spinal epidural hematomas in patients whose only apparent risk factor for the hematoma was their use of aspirin. These 3 cases are notable because the current guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA) for the placement of epidural and spinal catheters do not recommend cessation of these antiplatelet agents for epidural procedures; nor do the guidelines differentiate between the often disparate procedures for interventional pain and those performed for perioperative anesthesia/analgesia.3 There are several reasons why the issue of antiplatelet agents and possibly other anticoagulants for some chronic pain procedures (eg, percutaneous spinal cord stimulation lead placement) may need to be rethought. First, the procedure for spinal cord stimulation lead placement requires the use of very large bore 14-gauge needles with a long ramped bevel to enhance directional control. These needles are placed at shallow angles into the interlaminar opening and, quite commonly, there is a need to place 2 or more needles and sometimes even to replace the needles. This is done in the presence of fibrous adhesions, plica mediana dorsalis, scar, or spinal canal stenosis/anatomical narrowing that prevents passage of the lead in the anatomical midline from the point of epidural space entry. Second, the leads are stiff, styletted cylindrical objects with multiple electrode contacts (up to 16), and may require repeated manipulation to achieve optimal locations for stimulation paresthesias that are analgesic. As noted, this process can entail multiple changes of stylets, repeated retraction, and steering of the leads into different areas of the epidural space.2 When leads are retracted, as noted by Giberson and colleagues,1 there may be a risk for “snagging” the edge of the lead, causing a sharp edge. Third, it is not rare for the lead to move laterally within the epidural space or even to enter the anterior epidural space despite apparent midline placement during fluoroscopy in the anteroposterior plane. To some extent, this risk can be reduced by alternating biplanar imaging, particularly using the lateral view. It may be that the lateral or anterior areas of the epidural space, where veins may be more prevalent, are at greater risk for vascular trespass. In some cases, however, the targeted area may be the lateral “gutter” of the epidural space. Fourth, technology is changing as quickly as the number of new pharmaceutical agents for anticoagulation. There are other types of percutaneous leads that are more paddle-shaped being placed through introducers as well as ongoing trials of novel dorsal root ganglion leads,4 which are designed to intentionally exit the neural foramen with unknown cumulative risks of bleeding/vascular trespass. Finally, the safety of placing chronic long-term stimulation devices in patients who will need to resume anticoagulation remains largely uncertain. Worries about lead migration causing a rebleed remain. In the 2 cases described by Giberson and colleagues,1 the hematomas seemed to be related to the removal of the spinal cord stimulator (SCS) leads. One patient took an aspirin-containing medication the morning the leads were pulled out. It is possible that this unique patient developed a spinal hematoma the first time he complained of back pain and transient paraplegia the day after the electrodes were placed. Unfortunately, no imaging was performed in the emergency department to confirm or rule out this possibility. The other patient stopped aspirin and “other nonsteroidal anti-inflammatory drugs” a week before the trial. The leads were removed 4 days later, or 11 days after the antiplatelet medications were stopped. Bleeding after removal of catheters is known; the reasons include trauma to vascular structures during manipulation and/or dislodgement of a clot or in the setting of full anticoagulation.5–7 In fact, Vandermeulen et al8 noted that almost half of the cases of reported spinal hematoma occurred immediately after removal of the catheter, leading to the ASRA recommendations that the same guidelines should apply to both placement and removal
I
From the *Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL; and †Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN. Accepted for publication October 21, 2013. Address correspondence to: Marc A. Huntoon, MD, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN (e‐mail: [email protected]). The authors declare no conflict of interest. Copyright © 2014 by American Society of Regional Anesthesia and Pain Medicine ISSN: 1098-7339 DOI: 10.1097/AAP.0000000000000040
Regional Anesthesia and Pain Medicine • Volume 39, Number 1, January-February 2014
1
Copyright © 2013 American Society of Regional Anesthesia and Pain Medicine. Unauthorized reproduction of this article is prohibited.
Regional Anesthesia and Pain Medicine • Volume 39, Number 1, January-February 2014
Editorial
TABLE 1. Cases of Spinal Hematoma After Interventional Pain Procedures Intervention; Patient Profile
Report Franzini et al
Kloss et al11
Smith et al12
9
Medications
SCS placement; NSAIDs, 69-year-old man antiepileptics, antidepressants, opiates SCS placement; Not described 50-year-old man
Two cases, SCS placement; 44-year-old man and 66-year-old woman
Takawira et al13 SCS placement; 52-year-old man Williams et al14 CESI; 63-year-old man Ghaly15
CESI; 57-year-old man
Reitman and Watters,16
CESI; 62-year-old woman
Ain and Vance17
LESI; 85-year-old woman, renal insufficiency
Xu et al18
LESI; 78-year-old woman
Timing of Symptoms
Treatment and Outcome
Immediately after SCS
Laminectomy performed after MRI; recovery
Interval between SCS placement and symptoms not described
Laminectomy, partial recovery
Comments Coagulation studies normal
Article is a “Clinical Image” paper with minimal description of circumstance Neither patient on Symptoms on POD5 Laminectomy, no Coagulation antiplatelets in patient 1; recovery (T8 paraplegia) studies normal in or other immediately after in patient 1; full motor both patients anticoagulants procedure in recovery but with patient 2 numbness below T8 in patient 2 Not described Symptoms occurred No laminectomy, Repeat MRI 5 d later on third day of trial spontaneous recovery showed complete of sensory and motor resolution of hematoma functions Indomethacin and Within 2 h after Laminectomy, full INR, clotting time, allopurinol procedure recovery platelet count normal Diclofenac sodium, Within 30 min High-dose Coagulation studies amitriptyline of procedure methylprednisolone normal initially, laminectomy 10 h later; full recovery Fiorinal stopped Within 2 h Laminectomy 11 h after PT, PTT normal for 1 wk CESI; partial recovery complicated by CSF leak and meningitis, patient died Warfarin withheld 48 h after procedure Laminectomy 24–36 h Warfarin resumed 6 days, enoxaparin after symptoms + evening after ESI, withheld 24 h, dexamethasone for 3 d; enoxaparin INR 1.2 before ESI motor recovery, residual restarted 24 h later; numbness of left toes INR 1.2 next day Warfarin and aspirin Approximately Laminectomy within Warfarin restarted 8 h discontinued for 42 h after ESI few hours of symptoms; after ESI, enoxaparin 6 d, enoxaparin full recovery resumed 30 h later stopped for 24 h, INR normal
CESI indicates cervical epidural steroid injection; LESI, lumbar epidural steroid injection; epidural steroid injection; INR, international normalized ratio; MRI, magnetic resonance imaging; NSAIDs, nonsteroidal anti-inflammatory drugs; POD, postoperative day; PT, prothrombin time; PTT, partial thromboplastin time; SCS, spinal cord stimulator.
of epidural catheters.3 In the case reported by Buvanendran and Young,2 the patient began to experience symptoms the day after trial placement. She had continued aspirin (ASA), in accordance with the ASRA guidelines,3 but began to experience neurological signs before discharge after an overnight stay. A complete laboratory workup did not uncover other risk factors outside of the ASA.2 There are other reports of spinal hematomas associated with SCS placement or removal (Table 1).9–13 There are also case reports of spinal hematoma after epidural steroid injections in patients who were only on anti-inflammatory agents14,15 or aspirin,16 or despite the guidelines being followed (Table 1).17,18 Patients with chronic pain, in particular, may be on medications that can cause bleeding abnormalities. Although thrombocytopenia from carbamazepine is known, there are case reports of thrombocytopenia with oxcarbazepine.19 Although
2
the incidence of thrombocytopenia is lower after oxcarbazepine compared with carbamazepine (1.7% vs 2.9%), there is a significant negative correlation between the platelet count and the daily doses of both drugs.20 Valproate also causes thrombocytopenia, with the incidence around 18%.21 A significant negative correlation was also noted between valproate blood levels and platelet counts; female sex, patients older than 65 years, low baseline platelet counts, and dosages greater than 1000 mg/day were noted as risk factors.21,22 Thrombocytopenia after levetiracetam has also been reported.23 The tricyclic antidepressants seem not to cause bleeding but the selective serotonin reuptake inhibitors (SSRIs) have been associated with increased bleeding.24–28 The antiplatelet effect of SSRIs is related to its antagonism of the serotonin transporters or depletion of serotonin in the platelets, resulting in inhibition of serotonin-mediated platelet activation, or reduction in platelet counts.27,28 The degree of the antiplatelet effect of © 2014 American Society of Regional Anesthesia and Pain Medicine
Copyright © 2013 American Society of Regional Anesthesia and Pain Medicine. Unauthorized reproduction of this article is prohibited.
Regional Anesthesia and Pain Medicine • Volume 39, Number 1, January-February 2014
the SSRIs may be related to the drug’s degree of inhibition of serotonin reuptake.25,26 The absolute effect of SSRIs is moderate, about equivalent to low-dose ibuprofen.24 However, the combination of antiplatelet drugs increases the risk of bleeding.29 The anticoagulant effects of SSRIs and the other drugs used for pain management, although mild, are generally not known to clinicians. In fact, in the case reports of spinal hematoma after SCS placement, only the patients’ intake of “antiplatelets or other anticoagulants” was noted. The patients who developed spinal hematoma after epidural steroid injections were only on antiplatelet drugs (Table 1). Patients with back pain have spine abnormalities including spinal stenosis, with smaller capacity of their epidural spaces. The risks are magnified when patients take several medications including SSRIs, nonsteroidal anti-inflammatory drugs for acute exacerbation of radicular pain, and aspirin for cardiac or neurological reasons. The pain interventionalist may not be aware of these drug-induced changes and may proceed with their planned intervention despite the presence of these medications. This brings us back to the question posed by Giberson et al1 and Buvanendran and Young2 on developing separate ASRA guidelines for interventional pain procedures in patients on anticoagulants. Regional Anesthesia and Pain Medicine and ASRA have recommended that separate guidelines for pain be proposed, and a committee has been formed. The guidelines will have an international representation, with experts from the European Society of Regional Anesthesia and Pain Therapy and probably other societies participating in the formation of the guidelines. Although the guidelines may not be based on randomized studies or on large numbers of patients from pooled databases, it is hoped that they will provide reasonable recommendations and the evidentiary basis for such recommendations. The continuing safety of these procedures for our patients mandates that we take measured and reasonable actions on their behalf based on the best interpretation of existing literature. REFERENCES
Editorial
10. Santiago FM, Santiago J, Prieto M, et al. Dorsal epidural hematoma after implantation of a dorsal nerve stimulator (Spanish). Rev Esp Anestesiol Reanim. 2005;52:440–441. 11. Kloss BT, Sullivan AM, Rodriquez E. Epidural hematoma following spinal cord stimulator implant. Int J Emerg Med. 2010;3:483–484. 12. Smith CC, Lin JL, Shokat M, Dosanjh SS, Casthely D. A report of paraparesis following spinal cord stimulator trial, implantation and revision. Pain Physician. 2010;13:357–363. 13. Takawira N, Han RJ, Nguyen TQ, Gaines JD, Han TH. Spinal cord stimulator and epidural haematoma. Br J Anaesth. 2012;109:649–650. 14. Williams KN, Jackowski A, Evans PJD. Epidural haematoma requiring surgical decompression following repeated cervical epidural steroid injections for chronic pain. Pain. 1990;42:197–199. 15. Ghaly RF. Recovery after high-dose methylprednisolone and delayed evacuation. J Neurosurg Anesthesiol. 2001;4:323–328. 16. Reitman CA, Watters W. Subdural hematoma after cervical epidural steroid injection. Spine. 2002;27:E174–E176. 17. Ain RJ, Vance MB. Epidural hematoma after epidural steroid injection in a patient withholding enoxaparin per guidelines. Anesthesiology. 2005;102:701–703. 18. Xu RX, Bydon M, Gokaslan ZL, Wolinsky JP, Witham TF, Bydon A. Epidural steroid injection resulting epidural hematoma in a patient despite strict adherence to anticoagulation guidelines. J Neurosurg Spine. 2009;11:358–364. 19. Mahmoud J, Mathews M, Verna S, Basil B. Oxcarbazepine-induced thrombocytopenia. Psychosomatics. 2006;47:73–74. 20. Tutor-Crespo MJ, Hermida J, Tutor JC. Relation of blood platelet count during carbamazepine and oxcarbazepine treatment with daily dose, and serum concentrations of carbamazepine, carbamazepine-10,11-epoxide, and 10-hydroxycarbazepine. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007;151:91–94. 21. Nasreddine W, Beydoun A. Valproate-induced thrombocytopenia: a prospective monotherapy study. Epilepsia. 2008;49:438–445. 22. Conley EL, Coley KC, Pollock BG, Dapos SV, Maxwell R, Branch RA. Prevalence and risk of thrombocytopenia with valproic acid: experience at a psychiatric teaching hospital. Pharmacotherapy. 2001;21:1325–1330.
1. Giberson CE, Barbosa J, Brooks ES, et al. Epidural hematomas following removal of percutaneous spinal cord stimulator trial leads: two case reports. Reg Anesth Pain Med. 2014;39:73–77.
23. Oghlakian R, Nock C, Koubeissi M. A case of levetiracetam-induced thrombocytopenia. Epileptic Disord. 2010;12:335–337.
2. Buvanendran A, Young AC. Spinal epidural hematoma following spinal cord stimulator trial lead placement in a patient taking aspirin. Reg Anesth Pain Med. 2014;39:70–72.
24. de Abajo FJ, Rodriquez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population-based control study. BMJ. 1999;319:1106–1109.
3. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy. Reg Anesth Pain Med. 2010;35:64–101.
25. van Walraven C, Mamdani MM, Wells PS, Williams JI. Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ. 2001;323:655–658.
4. Deer TR, Grigsby E, Weiner RL, et al. A prospective study of dorsal root ganglion stimulation for the relief of chronic pain. Neuromodulation. 2013;16:67–72. 5. Janis KM. Epidural hematoma following postoperative epidural analgesia: a case report. Anesth Analg. 1972;51:689–692. 6. Helperin SW, Cohen DD. Hematoma following epidural anesthesia: report of a case. Anesthesiology. 1971;35:641–644. 7. Stevens DS. Epidural hematoma: was catheter removed during complete anticoagulation? Anesth Analg. 1992;75:863–864.
26. Meijer WEE, Heerdink ER, Nolen WA, Herings RMC, Leufkens HGM, Egberts ACG. Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants. Arch Intern Med. 2004;164:2367–2370. 27. Labos C, Dasgupta K, Nedjar H, Turecki G, Rahme E. Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. CMAJ. 2011;183:1835–1843.
8. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg. 1994;79:1165–1177.
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