Although an increased risk is recognized, epidural or spinal anesthesia has been considered a relatively safe procedure in patients having surgical revascularization and heparin therapy intraoperatively. However, this concept may need to be reevaluated because of the recent practice of infusing thrombolytic drugs intraarterially during vascular surgery . There are already reports of two cases of epidural hematomas in patients receiving thrombolytic therapy during continuous epidural anesthesia [2,3]; we report a patient who developed intrathecal bleeding during revascularization surgery after he received systemic heparin and an intraarterial infusion of urokinase during continuous spinal anesthesia.
A 75-yr-old male was admitted to the hospital because of pain and numbness of the right leg. He had been well until 1 mo prior to admission, when he developed intermittent claudication of the right leg when he walked farther than two blocks. He had a 50-yr history of hypertension, managed in recent years with nifedipine and furosemide. He had a 10-yr history of peripheral vascular disease for which he had undergone an aortobifemoral bypass graft 9 yr ago. On the day of the present admission he initially developed numbness and tingling and subsequently pain in the right leg, which he described as "feeling like a log." He was first taken to another hospital, where Doppler examination of the right extremity revealed the absence of blood flow in the popliteal, dorsalis pedis, and posterior tibial arteries. After initiation of treatment with unfractionated heparin, 5000 U administered as bolus followed by an infusion of 1000 U/h, he was transferred to Cook County Hospital.
Upon admission to the hospital the patient was in moderate distress, complaining of pain in the right foot. Arterial blood pressure was 190/90 mm Hg, heart rate 101 bpm, respiratory rate 22 breaths/min, and temperature 37.1 degrees C. The only positive physical findings were confined to the right lower extremity: there was decreased motor power (3/5) on the entire leg, there was decreased sensation in the foot, which was cold, and there was absence of popliteal, dorsalis pedis, and posterior tibial pulses.
Hemoglobin was 14 g/dL, hematocrit 42%, white cell count 9100/mm3 and a platelet count 111,000/mm3. The prothrombin time was 13.8 s, and the partial thromboplastin time was more than 150 s. Blood chemistries were all within normal limits, and a sickle-cell preparation was negative. A chest radiograph was normal, and an electrocardiogram showed sinus tachycardia at a rate of 108 bpm with occasional premature ventricular complexes.
The partial thromboplastin time was corrected with 12.5 mg of protamine prior to performing angiography, which revealed bilateral pseudoaneurysms of the femoral anastamoses with a thrombus/embolus occluding the lumen on the right. The patient was then taken to the operating room, where he arrived at 11:45 AM. After preparation and draping, a lumbar puncture was quickly accomplished, with a single insertion, at the L3-4 interspace using an 18-gauge Touhy needle, through which a 20-gauge spinal catheter was inserted 5 cm into the subarachnoid space. The procedure was atraumatic and a free-flow of clear cerebrospinal fluid (CSF) was obtained. At 12:35 PM 10 mg of hyperbaric bupivacaine was given in three divided doses over the next 30 min, and this resulted in a level of anesthesia at T8. Surgery started at 1:00 PM and at 1:52 PM, 5000 U of unfractionated heparin (Elkins-Sinn, Inc., Cherry Hill, NJ) was given intravenously. Shortly thereafter, the surgeons perfused the right femoral artery with 250,000 U of urokinase (Abbokinase Registered Trademark; Abbott Laboratories, North Chicago, IL). At 2:00 PM aspiration of CSF, prior to the administration of an additional 2.5 mg of bupivacaine, still showed clear fluid. However, at 3:30 PM, when another dose of local anesthetic was to be given, aspiration revealed a grossly bloody CSF which did not clear even after the catheter was flushed twice with saline. When the surgeons were informed of this finding, they decided to terminate the surgery after repairing only the right femoral pseudoaneurysm. The vital signs had been stable throughout the procedure until 4:30 PM, when the systolic blood pressure, which had remained in the range of 170-180 mm Hg until this time, decreased to 140-150 mm Hg with a small increase in the heart rate. The estimated blood loss at this time was 1000 mL, and the replacement consisted of 3800 mL of crystalloid solutions and 500 mL of colloid. The urinary output was 1520 mL. The hemoglobin was 7.5 g/dL, and the arterial blood gases and electrolytes were within normal limits. At 4:45 PM the prothrombin time was 15.4 s and the partial thromboplastin time more than 150 s. The hemoglobin had decreased to 5.9 g/dL, the hematocrit to 17.5%, and the platelet count to 49,000/mm3. The patient was transfused with 2 U of packed red blood cells and 2 U of fresh frozen plasma because of poor hemostasis, despite the use of thrombin locally.
At 7:15 PM, after hemostasis had been achieved and the surgical incision closed, the patient was transferred to the surgical intensive care unit. The intrathecal catheter was left in place to allow decompression of increased intrathecal bleeding postoperatively if necessary. The patient was awake, alert, and complaining of mild shortness of breath, but without chest pain or hemoptysis. Arterial blood pressure was 130/70 mm Hg, heart rate 106 bpm, respiratory rate 20 breaths/min and the central venous pressure 5 cm H2 O. The dressing covering the area where the central line was inserted was now soaked with blood. At 8:45 PM the prothrombin time was 13.3 s, the partial thromboplastin time 25.9 s, the hemoglobin 8.1 g/dL, the hematocrit 24.3%, and the platelets 41,000/mm3. Aspiration of the intrathecal catheter showed again a blood-tinged CSF. The patient was given 8 mg of dexamethasone intravenously.
On the first postoperative day the hemoglobin was 8.7 g/dL, the hematocrit 25.6%, and the platelet count 116,000/mm3. Examination of the CSF showed 10,000 red blood cells/mm3, a Cl- level of 129 mmol/L, a glucose of 67 mg/dL, and a protein of 85 mg/dL. The intrathecal catheter was removed on the second postoperative day. The patient was discharged to the surgical ward on the third postoperative day, and he was discharged home on the sixth postoperative day.
Our patient developed thrombocytopenia, associated with the intrathecal bleeding, as evidenced by two consecutive platelet counts less than 100,000/mm3 24 h after the start of heparin therapy. Early thrombocytopenia, a frequent complication of heparinization which is not associated with heparin-dependent immunoglobulin G antibodies or with the type of heparin used , is reversible despite continuation of heparin therapy. In fact, the platelet count returned to basal levels on the third day of heparin treatment. The fact that clear CSF was obtained 90 min after the placement of the spinal catheter and before the intraoperative use of urokinase suggests that thrombocytopenia did not play a primary role in causing the intrathecal bleeding.
Urokinase, an enzyme produced by the kidney, is used for the treatment of acute arterial thrombosis, embolism, graft occlusion, and is also used as an adjuvant for surgical revascularization . Thrombolytic drugs such as urokinase, streptokinase, or recombinant tissue plasminogen activator activate plasminogen to plasmin, a proteolytic enzyme that hydrolyzes fibrin, resulting in the lysis of thrombi. Patients receiving thrombolytic therapy are at slightly increased risk (1.04% vs 0.86% for control subjects) for the development of intracranial hemorrhage, such as parenchymatous intracerebral hemorrhage, subdural hematoma, hemorrhagic infarction, and subarachnoid hemorrhage [6,7]. When blood penetrates the subarachnoid space, it produces irritation of the meninges, stimulation of pain fibers, and a sudden increase in intracranial pressure. The corresponding symptoms include severe headache, often with nausea and vomiting, stiff neck, and occasionally loss of consciousness. The lack of any of these symptoms in our patient indicates that the bloody CSF was probably due to bleeding at the level of the spinal catheter insertion. Similar findings were reported in a study involving patients with acute myocardial infarction who were treated with thrombolytic drugs. In over 70% of the patients who hemorrhaged, the primary bleeding site was at the catheter or other puncture site . In fact our patient also bled through the site of insertion of the central line catheter.
Intrathecal bleeding may evolve into another type of complication. Blood in the CSF can lead to the development of spinal arachnoiditis, a severe pain syndrome of the low back and legs that is extremely difficult to treat.
If parenchymatous intracerebral hemorrhage, subarachnoid hemorrhage, or subdural hematoma is documented after thrombolytic therapy, the patient should be given 10 U of cryoprecipitate, which in a 70-kg adult will increase the fibrinogen level by 75 mg/dL and the factor VIII level by 30%. Fresh frozen plasma, 12-15 mL/kg, may be used as a source of factors V and VIII. Reversal of heparin with protamine is not indicated in a patient with no neurologic symptoms or focal findings due to the risk of graft reclotting. In rare cases, antifibrinolytic agents, such as epsilon-aminocaproic acid or aprotinin, may be necessary, but this approach may theoretically be complicated by graft reocclusion.
If thrombolytic therapy is proven to be effective as an adjuvant in surgical revascularization, a prospective study is needed to determine the incidence of complications in patients receiving regional anesthesia as compared to general anesthesia. Pending such a study, anesthesiologists should carefully weigh the risks and benefits of continuous spinal anesthesia in a patient who is likely to receive thrombolitic therapy while the catheter is in place.
1. Lonsdale RJ, Whitaker SC, Berridge DC, et al. Peripheral arterial thrombolysis: intermediate-term results. Br J Surg 1993;80:592-5.
2. Dickman CA, Shedd SA, Spetzler RF, et al. Spinal epidural hematoma associated with epidural anesthesia: complications of systemic heparinization in patients receiving peripheral vascular thrombolytic therapy. Anesthesiology 1990;72:947-50.
3. Onishchuk JL, Carlsson C. Epidural hematoma with epidural anesthesia: complications of anticoagulant therapy. Anesthesiology 1992;77:1221-3.
4. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330-5.
5. Fratantoni JC, Ness P, Simon TL. Thrombolytic therapy: current status. N Engl J Med 1975;293:1073-8.
6. Sloan MA. Stroke associated with thrombolytic therapy for acute myocardial infarction. Heart Disease and Stroke 1992;1:287-94.
7. Tiefenbrunn AJ, Ludbrook PA. Coronary thrombolysis--it's worth the risk. JAMA 1989;261:2107-8.
8. Rao AK, Pratt C, Berke A, et al. Thrombolysis in myocardial infarction (TIMI) trial--phase I: hemorrhagic manifestations and changes in plasma plasminogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol 1988;11:1-11.