Patients with an altered level of consciousness, a focal neurologic deficit, new-onset seizure, papilledema, or an immunocompromised state are at increased risk for potentially fatal cerebellar or tentorial herniation following LP. Neuroimaging should be obtained in these patients prior to LP to exclude a focal mass lesion or diffuse swelling. Imaging studies should include the spine in patients with symptoms suggesting spinal cord compression, such as back pain, leg weakness, urinary retention, or incontinence. In patients with suspected meningitis who require neuroimaging prior to diagnostic LP, administration of antibiotics, preferably following blood culture, should precede the neuroimaging study.
LP should not be performed through infected skin, as organisms can be introduced into the subarachnoid space (SAS).
Patients with coagulation defects including thrombocytopenia are at increased risk of post-LP spinal subdural or epidural hematomas, either of which can produce permanent nerve injury and/or paralysis. If a bleeding disorder is suspected, the platelet count, international normalized ratio (INR), and partial thromboplastin time (PTT) should be checked prior to LP. There are no data available to assess the safety of LP in patients with low platelet counts; a count of <20,000/μL is considered to be a contraindication to LP, and some institutions recommend that the platelet count be >40,000 prior to LP. Bleeding complications rarely occur in patients with platelet counts ≥50,000/μL and an INR ≤1.5.
GUIDELINES FOR PATIENTS RECEIVING ANTICOAGULANT OR ANTIPLATELT MEDICATIONS
There is an increased risk of bleeding complications if an LP is performed in a patient receiving antiplatelet or anticoagulant medications. The risk is further increased when multiple anticoagulant medications are used or when the level of anticoagulation is high. The most common site of bleeding is the epidural space. Symptoms of bleeding following an LP can include a sensory or motor deficit and/or bowel/bladder dysfunction; back pain occurs less commonly. For serious deficits such as paraparesis, immediate surgical intervention, ideally within 8 h of onset of weakness, is important to minimize permanent disability; surgical intervention after 24 h is associated with a poor outcome.
Only limited data are available to guide decisions about performing LPs in patients receiving anticoagulant drugs. Information about managing antiplatelet and anticoagulation drugs during invasive surgical procedures is available from the prescribing information provided by the drug manufacturer. Evidence-based guidelines for management of regional anesthetic procedures including spinal and epidural blocks and for management of interventional spine and pain procedures in patients receiving anticoagulation have been developed by the American Society of Regional Anesthesia and Pain (ASRA); these guidelines can help guide decisions by physicians considering LP. Management of these patients can be complex and needs to consider both the risk of LP-related hemorrhage as well as the risk of reversing therapeutic anticoagulation prior to LP. Guidelines for some commonly used anticoagulants are summarized below.
Unfractionated Heparin (UFH), Therapeutic Dosing
The ASRA 2010 Practice Advisory recommends discontinuing UFH 2–4 h prior to removal of spinal or epidural catheters to minimize risk of hematoma. Similar guidelines are reasonable for patients undergoing LP: discontinue UFH 2–4 h prior to LP; document normal PTT prior to the procedure; and document a normal platelet count in patients who have received heparin for 4 days or longer because of the risk of heparin-induced thrombocytopenia (HIT). The half-life of heparin is 60–90 min.
There have been case reports of spinal hematoma resulting from spinal or epidural anesthetic procedures in patients receiving low-dose subcutaneous UFH. The 2010 ASRA guidelines for regional anesthetic procedures stated that there is no contraindication to the use of these techniques for anesthesia in patients receiving prophylactic UFH at a dose of 5000 U subcutaneously twice daily. However, the 2015 ASRA guidelines for interventional spine and pain procedures recommend discontinuing subcutaneous heparin for 8–10 h before a planned neuraxial procedure. Similar precautions to prevent bleeding should be taken prior to LP in patients receiving 5000 U of UFH subcutaneously twice daily: document a normal PTT prior to the LP; document a normal platelet count in patients who have received heparin for 4 days or longer; and perform the LP 1–2 h prior to the next heparin dose, when the heparin effect should be minimal. Subcutaneous heparin can be usually resumed 2 h after an uncomplicated procedure.
Low-Molecular-Weight Heparin (LMWH), Therapeutic Dose (e.g., Enoxaparin 60 mg Subcutaneously q12h)
Patients receiving LMWH are at increased risk of post-LP spinal or epidural hematoma. LMWH dose should be held for at least 24 h before the procedure.
LMWH, Prophylactic Dose (e.g., Enoxaparin 30 mg Subcutaneously q12h)
Patients receiving prophylactic dose LMWH have altered coagulation. ASRA guidelines recommend waiting at least 10–12 h after a prophylactic dose of LMWH before inserting a spinal or epidural catheter to minimize the risk of spinal or epidural hematoma. Similar guidelines are reasonable for patients undergoing LP.
Spinal puncture is contraindicated during warfarin therapy. Warfarin should be stopped 4–5 days prior to the LP, and for urgently needed procedures, warfarin’s effect can be reversed with fresh frozen plasma. The INR should be within the normal range at the time of the procedure.
Aspirin and Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
ASRA guidelines conclude that use of these drugs does not appear to be associated with a significant added risk of spinal bleeding in patients having spinal or epidural anesthesia. Similarly, LP in patients receiving one of these drugs is unlikely to cause bleeding. Reversal of drug effect on platelet function requires stopping the drug for ~10 days for aspirin, 4 days for naproxen, and 24 h for ibuprofen.
ASRA guidelines developed for regional anesthetic procedures suggest discontinuing ticlopidine 14 days prior to a spinal or epidural procedure and discontinuing clopidogrel 7 days prior to the procedure. Similar guidelines are reasonable for performing LP.
Abciximab, Eptifibatide, and Other Platelet Glycoprotein IIb/IIIa Inhibitors
The risk of spinal hematoma with these drugs is unknown. Platelet aggregation remains abnormal for 24–48 h following discontinuation of abciximab and 4–8 h following discontinuation of eptifibatide. ASRA guidelines for regional anesthetic procedures recommend avoiding spinal or epidural procedures until platelet function is normal. Similar guidelines are reasonable for performing LP.
Direct Thrombin Inhibitors (e.g., Dabigatran)
Pradaxa® prescribing information includes a boxed warning about the risk of epidural or spinal hematoma in patients treated with Pradaxa who are receiving neuraxial anesthesia or undergoing spinal puncture. For medium- and high-risk interventional pain procedures, where the risk of bleeding may be similar to LP, ASRA guidelines recommend an interval of 4–5 days between discontinuation of dabigatran and the interventional pain procedure, and an interval between the procedure and resumption of dabigatran of 24 h. Similar guidelines for performing LP are not available. For emergency situations in which rapid reversal of the anticoagulant effect of dabigatran is indicated, idarucizumab, a humanized monoclonal antibody fragment, is U.S. Food and Drug Administration (FDA) approved as a specific reversal agent for dabigatran. The half-life of dabigatran is 8 h after a single dose and 17 h after multiple doses.
Oral Factor Xa Inhibitors
Xarelto® prescribing information includes a boxed warning about the risk of spinal/epidural hematoma with spinal puncture. LP should be avoided in patients receiving this drug. The half-life of rivaroxaban is 9–13 h. Xarelto® prescribing information states that indwelling epidural or intrathecal catheters not be removed before at least 2 half-lives have elapsed, i.e., 18 h in young patients aged 20–45 years and 26 h in elderly patients aged 60–76 years, after the last administration of rivaroxaban. Rivaroxaben should not be resumed earlier than 6 h after removal of the catheter. If traumatic puncture occurs, resumption of rivaroxaban should be delayed for 24 h. Similar guidelines are reasonable for performing LP.
Eliquis® prescribing information includes a boxed warning about the risk of spinal/epidural hematoma with spinal puncture. LP should be avoided in patients receiving this drug. The effect of apixiban is expected to last for at least 24 h after the last dose, i.e., for about 2 drug half-lives. Eliquis® prescribing information recommends that indwelling epidural or intrathecal catheters not be removed earlier than 24 h after the last administration of apixiban. Apixiban should not be resumed earlier than 5 h after removal of the catheter. If traumatic puncture occurs, resumption of apixiban should be delayed for 48 h. Similar guidelines are reasonable for performing LP.
Arixtra® prescribing information includes a boxed warning about the risk of spinal/epidural hematoma with neuraxial anesthesia or spinal puncture. ASRA guidelines for interventional spine and pain procedures recommend stopping fondaparinux for 3–4 days before a medium- or high-risk pain procedure. Similar guidelines are reasonable for performing LP.