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��ࡱ�>��	mo����l�������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������[�	��s|bjbj����	4~ΐΐ7������������������������$�W"����������!�!�!�!�!�!�!$!$��&B�!9�������!�����"RRR������!R��!RRR�����5�T'���R�!'"0W"R'�f'R'�RL��R������!�!R���W"������������������������������������������������������������������������'����������	�:	@Title: �Safety of Spinal Anesthesia in patients with recent coronary stent: case report�
Running title: �Coronary stent and spinal anaesthesia�

Summary:
Complications related to spinal anaesthesia following antiplatelet therapy is not clear. We report a patient with known history of Chronic obstructive airway disease with respiratory tract infection who presented for emergency pseudoaneurysm repair. He underwent recent coronary stent implantation and was treated with Clopidogrel and Aspirin. Despite dual antiplatelet therapy, spinal anaesthesia was administered safely with prior platelet transfusion. Thus regional anaesthesia can be considered in selected patients with prior platelet transfusion in patients on dual antiplatelet drugs when it is deemed necessary.

Keywords: Coronary stent, Antiplatelet drugs, Chronic obstructive airway disease, Pseudoaneurysm


Introduction:
Anaesthesiologists are increasingly confronted with patients who had a recent coronary artery stent implantation and are on dual anti-platelet medication. Non cardiac surgery and most invasive procedures increase the risk of stent thrombosis especially when procedure is performed early after stent implantation. Dual antiplatelet therapy presents problems for regional anaesthesia. We present a case anticoagulated with both Clopidogrel and Aspirin who required urgent surgery. Spinal anaesthesia was planned because of Chronic obstructive airway disease and difficult airway situation, despite the increased risk for epidural haematoma secondary to antiplatelet therapy. 


Case report:
A 44 year gentleman presented with history of swelling and redness in right groin. He underwent cardiac catheterization for coronary stent implantation through right femoral route ten days back. His past illness revealed on and off exacerbation of chronic obstructive airway disease (COAD) with recent onset of lower respiratory tract infection. Furthermore, he had coronary artery disease (CAD) with angina at moderate physical activity, which had been treated by angioplasty and stent implantation. He was anticoagulated with Clopidogrel (75 mg twice daily) and Aspirin (300 mg daily) since the day of stent implantation. He had no other medical illness.
On local examination of the right groin, an expansile swelling with multiple puncture points visualized over the swelling. The skin over the swelling was edematous and it extends upto the right middle of thigh. Urgent Ultrasonography of thigh revealed ill-defined hyperechoic soft tissue swelling superficial to the femoral vessels without any distortion in the vessel calibre proximal and distal to the swelling suggestive of haematoma. Patient was admitted in the Intensive Care Unit (ICU) with continuation of all anticoagulants and next day Magnetic Resonance Angiography (MRA) revealed pseudoaneurysm of common femoral artery [Figure 1].
In view of the increasing in size of the groin swelling, patient was planned for urgent exploration of the haematoma and repair of the pseudoaneurysm. Pre-operative routine investigations were within normal limit. Coagulation studies revealed Prothrombin time (PT) 15.9 sec, International normalized ration (INR) 1.33, Platelet count 2,64 x 103/�L, Coagulation time 240 sec and Clot formation time 80 sec. Due to the patients COAD with ongoing respiratory tract infection and difficult airway situation (Modified Mallampati classification III with Thyromental distance 5cm), surgery was planned under spinal anaesthesia rather than general anaesthesia despite antiplatelet therapy.  
Patient was taken to the operation theatre and a large bore intravenous line and left radial artery cannulation done under local anaesthesia. Two units of pooled platelet concentrate (each one containing about 2 x 109 platelet) were infused. Post transfusion platelet count increased by 3,00 x 103/�L and both coagulation time and clot formation time shortened to 110 sec and 30 sec respectively. Spinal anaesthesia administered at Lumber 4-5 interspace using 25 gauze needle in single attempt. 15 mg (3ml) hyperbaric Bupivacaine with Morphine 5�g/kg produced anaesthesia extending upto Thoracic-10 dermatome and surgery performed safely.
Postoperatively patient was kept in ICU for monitoring and there was no evidence of subsequent epidural haematoma such as neurological deficits and back pain.

Discussion:

Coronary stents are placed in up to 90% of all percutaneous coronary interventions (PCI)1 because they increase procedural success and decrease restenosis 2. Roughly 5% of these patients will present for noncardiac surgery within the first twelve months after stenting 3. Anaesthetists are faced with the peri-operative dilemma of managing patients on dual antiplatelet therapy � stop the drugs and risk of life threatening stent thrombosis, or continue therapy and risk of potentially disastrous bleeding. Although heparin therapy is often used perioperatively for thromboembolic prophylaxis, it does not have antiplatelet properties and is not protective against stent thrombosis 4. Further, �heparin rebound� occurs after abrupt cessation of an unfractionated heparin (UFH) infusion 5. Vicenzi et al. described an association between perioperative heparin therapy and increased cardiac morbidity and mortality among patients with coronary stents 6.

Dual antiplatelet therapy presents problems for regional anaesthesia. The placement of neuro-axial block in patients taking dual antiplatelet therapy cannot be recommended unless platelet function is within acceptable limits or platelet transfusion is given before operation 7. The guidelines produced in 2003, by American Society Regional Anaesthesia (ASRA) that without prior platelet transfusion Clopidogrel should be stopped for minimum of 7 days and Ticlopidine for a minimum of 14 days 8. 

 According to ASRA, treatment with nonsteroidal anti-inflammatory drugs like aspirin alone is no contraindication to neuraxial anaesthesia. The German Society of Anaesthesiology and Intensive Care Medicine recommend an interval of three days between Aspirin application and spinal anaesthesia, but a consensus statement on neuraxial blockade and thienopyridine therapy has not been presented 9. Thus, no guidelines exist for administration of central neural blockade in patients receiving combination antiplatelet therapy, although dual application of Clopidogrel and Aspirin significantly increases bleeding time 10. The impact of aspirin on surgical bleeding has been primarily studied in cardiac and vascular surgery 11. The likelihood of increased bleeding and/or an increased requirement for blood transfusion in patients undergoing major noncardiac surgery while taking Clopidogrel has largely been inferred from the cardiac surgical literature, which contains conflicting data 12. 

Evidence regarding safety of spinal/epidural anaesthesia in patients on Clopidogrel is also scarce but most anaesthetists will not perform a spinal anaesthetic within 7 days of the last dose of Clopidogrel because of the risk of spinal haematoma 13. In fact, a case of spinal subarachnoid haematoma after epidural anaesthesia in a patient receiving the platelet aggregation inhibitor ticlopidine has been reported 14.

Nevertheless, co-existing disease may make a spinal or epidural technique preferable, as in our patient with severe pulmonary disease, and temporary improvement of platelet function is thus desirable. This led us to monitor the effects of platelet transfusion with all available tests. Based on the current information available, the decision to perform regional anaesthesia should be made case-by-case, with consideration given to all potential complications. The anaesthetist has to choose between keeping the protective effect of Clopidogrel and proceeding with general anaesthesia, or stopping it for at least 7 days before the operation to perform a neuraxial block and benefit from its sympatholytic and analgesic effects.

If the surgery involves a high risk of haemorrhage, or if regional neuraxial blockade is thought to be essential, it may be necessary to give a platelet transfusion before surgery. The French Health Products Safety Agency reviewed the issue of perioperative platelet transfusion in 2003 and made the following recommendations: 15, 16 for commonly practised invasive procedures transfuse to achieve a platelet count of >50 000 �L-1, in the absence of platelet dysfunction, for surgery with a standard haemorrhagic risk ensure a platelet count >50 000 �L-1, for neurosurgery and ophthalmic surgery involving the posterior segment of the eye a platelet count of >100 000 �L-1 is required, for neuraxial regional anaesthesia a platelet count of 50000 �L-1  is sufficient for spinal anaesthesia, with 80000 �L-1  proposed for epidurals. The plasma half-life of Clopidogrel is short, so inhibition of transfused platelets should not be a clinically relevant issue and Clopidogrel therapy only results in a maximum of 40�60% inhibition of aggregation 17. Each unit of platelet concentrate is known to raise the platelet count by a minimum of 5000 �/L under normal circumstances. However, some experts believe the above transfusion thresholds to be too high 18. There is a case report of uneventful spinal anaesthesia after a two unit platelet transfusion in a patient taking Clopidogrel and Aspirin who required urgent surgery, with the rise in the platelet count documented as 24 000 �L-1 like our case. 19
In conclusion, spinal anaesthesia was performed safely in a patient with dual antiplatelet drug for emergency surgical procedures following platelet transfusion. Platelet transfusion is a reasonable way to improve coagulation function quickly in selected patients on antiplatelet drugs planning for central neuralxial blockade.    


Reference:

1. Metzler H, Kozek-Langenecker S, Huber K. Antiplatelet therapy and coronary stents in perioperative medicine � the two sides of the coin. Best Practice & Research Clinical Anaesthesiology 2008; 22: 81�94

2. Brilakis ES, Banerjee S, Berger P. Perioperative Management of Patients with Coronary Stents. Journal of the American College of Cardiology 2007. 49: 2145�50

3. Chassot P, Delabays A, Spahn DR. Perioperative use of anti-platelet drugs. Best Practice & Research Clinical Anaesthesiology 2007; 21: 241�256

4. Collet JP, Montalescot G. Premature withdrawal and alternative therapies to dual oral antiplatelet therapy. Eur Heart J Suppl 2006;8(Suppl):G46�G52

5. The�roux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med 1992;327:141�5

6. Vicenzi MN, Meislitzer T, Heitzinger B, Halaj M, Fleisher LA, Metzler H. Coronary artery stenting and non-cardiac surgery�a prospective outcome study. Br J Anaesth 2006;96:686�93

7. Usha Kiran, Neeti Makhija. Patient with Recent Coronary Artery Stent Requiring Major Non Cardiac Surgery. Indian Journal of Anaesthesia 2009; 53 (5):582-591

8. Harlocker TT, Wedel DJ, Benzon H, et al. Regional anesthesia in the anticoagulated patient: defining the risk (The second ASRA Consensus Conference on Neuraxial Anasthesia and Anticoagulation) Reg Anesth Pain Med 2003; 28: 172-97.

9. Gogarten W, VanAken H, Wulf H, Klose R, Vandermeulen E, Harenberg J. Para-spinal regional anesthesia and prevention of thromboembolism D  anticoagulation. Recommendations
of the German Society of Anesthesiology and Intensive Care Medicine. Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie: AINS 1997; 38: 623�8.

10. Payne DA, Hayes PD, Jones CI, Belham P, Naylor AR, Goodall AH. Combined therapy with clopidogrel and aspirin significantly increases the bleeding time through a synergistic antiplatelet action. Journal of Vascular Surgery 2002; 35: 1204�9.

11. Burger W, Chemnitius JM, Kneissl GD, Rucker G. Low-dose aspirin for secondary cardiovascular prevention�cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation�review and meta-analysis. J Intern Med 2005;257:399�414.

12. Grines CL, Bonow RO, Casey DE Jr, Gardner JT, Lockhart PB, Moliterno DJ, O�Gara P. Whitlow P. AHA/ACC/SCAI/ ACS/ADA Science Advisory. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. A science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation 2007;115: 813�18.

13. Horlocker TT, Wedel DJ, Benzon H, et al. Regional anesthesia in the anticoagulated patient: defining the risks. (the second ASRA consensus conference on neuraxial anesthesia and anticoagulation). Reg Anesth Pain Med 2003;28(3):172�97.

14. Mayumi T, Dohi S. Spinal subarachnoid hematoma after lumbar puncture in a patient receiving antiplatelet therapy. Anesthesia and Analgesia 1983; 62: 777�9.

15. Samama CM, Djoudi R, Lecompte T, Nathan-Denizot N, Schved JF. Perioperative platelet transfusion: recommendations of the Agence Francaise de Securite Sanitaire des Produits de Sante (AFSSaPS) 2003. Can J Anaesth 2005; 52: 30�7

16. Samama CM, Djoudi R, Lecompte T, Nathan N, Schved JF. Perioperative platelet transfusion. Recommendations of the French Health Products Safety Agency (AFSSAPS) 2003. Minerva Anestesiol 2006; 72: 447�52

17. Harder S, Klinkhardt U, Alvarez JM. Avoidance of bleeding during surgery in patients receiving anticoagulant and/or antiplatelet therapy: pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet 2004; 43: 963�81

18. Heal JM, Blumberg N. Optimizing platelet transfusion therapy. Blood Rev 2004; 18: 149�65

19. Herbstreit F, Peters J. Spinal anaesthesia despite combined clopidogrel and aspirin therapy in a patient awaiting lung transplantation: effects of platelet transfusion on clotting tests. Anaesthesia 2005; 60: 85�7


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