Successful Rescue Thrombolysis in Massive Pulmonary Embolism with Intracerebral Hemorrhage Audrey De Jong, MD,* Alain Boularan, MD,* Frédéric Greco, MD,* Kifah Khouri, MD,† and Pierre-François Perrigault, MD* We report the case of a man with a massive pulmonary embolism, which lead to cardiac arrest. After ruptured aneurysm clipping, he was successfully treated by rescue thrombolysis administered as compassionate treatment despite the risk of cerebral bleeding. The patient was discharged from the intensive care unit; his initial neurological, cardiac, and pulmonary conditions restored. In case of life-threatening pulmonary embolism, the risk–benefit ratio of thrombolysis therapy should be systematically evaluated and the decision adapted to each patient. (A&A Case Reports 2013;1:31–3)
I
ntracerebral hemorrhage (ICH) is a dreaded complication of thrombolytic therapy. Published guidelines related to use of antithrombotic and thrombolytic therapy for ischemic stroke1 report an incidence of symptomatic ICH after thrombolytic therapy in acute ischemic stroke of 7.3% compared with 5.9% in stroke trials. Additional guidelines recommend against thrombolysis for the treatment of stroke2 or pulmonary embolism3 after recent intracranial surgery. We describe successful thrombolytic treatment of massive bilateral pulmonary embolism occurring several hours after intracranial aneurysm clipping for a ruptured intracranial aneurysm. The local scientific and ethics committee of Comite d’Organisation et de Gestion de l’Anesthesie-Reanimation du Centre Hospitalier Universitaire de Montpellier approved the case report. We obtained patient permission to publish this case report.
CASE DESCRIPTION
A 71-year-old conscious and oriented man was admitted to the Montpellier University Hospital’s Stroke Center after 5 days of severe headache. The cerebral computed tomography (CT) scan revealed a right frontotemporal subarachnoid hemorrhage and a cerebral aneurysm of the right middle cerebral artery. Embolization of the aneurysm was scheduled 1 day later, but before it could be performed, the patient presented left hemiplegia with a Glasgow coma score of 7 (eyes, 2; verbal, 2; motor, 3). After tracheal intubation, repeat CT scan revealed a large ICH (Fisher grade 4) and he underwent emergent aneurysm clipping and i nsertion of external ventricular drain. From the Departments of *Intensive Care Unit (DAR C) and †Neurosurgery, Gui de Chauliac Hospital, University Hospital of Montpellier, Montpellier cedex, France. Accepted for publication March 07, 2013. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Audrey De Jong, MD, Unité de RéanimationDépartement d’Anesthésie-Réanimation “C”, University hospital. Chu de Montpellier Hopital Gui de Chauliac Hospital, 80 Ave. Augustin Fliche, 34295 Montpellier Cedex 5, France. Address e-mail to audreydejong@ hotmail.fr. Copyright © 2013 International Anesthesia Research Society DOI: 10.1097/ACC.0b013e318293d95b
October 15, 2013 • Volume 1 • Number 2
Four hours after admission to the intensive care unit (ICU), and while sedated with midazolam and fentanyl, he became hypoxemic and hemodynamically unstable. Cardiac ultrasound showed a dilated right ventricle, and lung CT scan with injection of contrast confirmed a massive pulmonary embolism. The coagulation data were normal with a prothrombin time (PT) at 12.3 seconds, activated partial thromboplastin time (APTT) at 24 seconds (ratio = 0.9), fibrinogen at 4.2 g/L, and 2,32,000/mm3 blood platelets. A cerebral CT scan was also performed (Fig. 1A). After discussion with the thoracic surgeon, surgical thrombectomy was not recommended. His hemodynamic state worsened quickly until cardiac arrest (pulseless electrical activity) occurred. Immediate resuscitation was instituted using 2 mg epinephrine and 1 minute of external cardiac compression (0 minutes of no flow and 1 minute of low flow) restored his arterial blood pressure to 110/60 mm Hg. Rescue fibrinolysis (alteplaserecombinant tissue plasminogen activator [rTPA]) was performed using an IV bolus of 10 mg followed by 40 mg in 30 minutes (patient weight: 80 kg, i.e., 0.6 mL/kg), through the right subclavian central venous access. Additional therapy using nonfractioned heparin and intermittent pneumatic compression was then started as a backup. In the evening, his PT was at 12.8 seconds and his APTT at 28.9 seconds (ratio = 1), with a fibrinogen at 4.4 g/L. The day after, under heparin therapy, the APTT was at 90.8 seconds (ratio = 2.7) and PT at 13.8 seconds. His hemodynamic variables were monitored by an echocardiography pulmonary artery catheter. Two hours after resuscitation, his cardiac output was 2 L/min. The urine output without diuretic therapy and the lactates (2 mmol/L) were normal. We used norepinephrine to maintain mean arterial blood pressure >65 mm Hg. Two days later, his cardiac output was 3.5 L/min with a gradient between the right ventricle and right atrium of 38 mm Hg, and a control CT scan showed worsening ICH and intraventricular bleeding (Fig. 1B). During his stay, the APTT was maintained between 70 and 90 to achieve a ratio between 2 and 3. The PT remains stable between 13.7 and 12.9 seconds. Regular CT scans were performed to monitor the intracerebral bleeding, and intracranial pressure was assessed every hour using an intraventricular catheter. His intracranial pressure remained low, and no cerebrospinal fluid was removed. cases-anesthesia-analgesia.org
31
When Benefits Outweigh the Risks...
A
Cerebral hemorrhage after clipping and before fibrinolysis
B
C
Cerebral hemorrhage recurrence two days after fibrinolysis
Cerebral hemorrhage disappearance one month after fibrinolysis
Figure 1. Brain computed tomography evolution before, 2 days after and 1 month after fibrinolysis. A, Cerebral hemorrhage after clipping and before fibrinolysis. B, Cerebral hemorrhage recurrence 2 days after fibrinolysis. C, Cerebral hemorrhage disappearance 1 month after fibrinolysis.
After 2 weeks of mechanical ventilation due to a persistent lung infection, the sedation was stopped and the patient regained consciousness 1 day later. His cardiac output was estimated at 5 L/min without pulmonary arterial hypertension. At day 28, his trachea was successfully extubated and cerebral tomography showed the disappearance of the intraventricular hemorrhage (Fig. 1C). At day 33, he was discharged from the ICU. He had a slight motor deficit in the left arm, was perfectly conscious, oriented, and did not require oxygen. One month later, he was discharged from the hospital and sent home, his blood anticoagulated with a vitamin K antagonist.
DISCUSSION
Massive pulmonary embolism leading to cardiac arrest a few hours after clipping of cerebral aneurysm is uncommon. We present a case of such a patient successfully treated by rescue fibrinolysis (alteplase-rTPA). Indeed, 1 month after the fibrinolysis, the patient was discharged from the ICU with his neurological state restored and good cardiac and pulmonary functions. A review related the use of alteplase for stroke beyond the guidelines4 and described 5 patients with an unruptured aneurysm who received IV alteplase for stroke.5 Two of them had a fatal ICH. During liver transplantation, Boone et al.6 reported the successful use of low-dose rTPA (0.5–4 mg) administration in 4 patients for the treatment of intracardiac thrombosis and pulmonary embolism. In our case, recent clipping of a ruptured aneurysm was an absolute contraindication to thrombolysis.3 However, in patients with massive and hemodynamically unstable pulmonary embolism, thrombolytic therapy has shown to rapidly improve their hemodynamics.3,7 Thus, in this case recognizing the risk of administering thrombolytic therapy, and faced with an immediate life-threatening situation, we chose to administer alteplase as a compassionate rescue
32 cases-anesthesia-analgesia.org
therapy. The dose of alteplase was 0.6 mL/kg, as advised in case of extremely severe pulmonary embolism.7 Alternative approaches other than we used and as suggested by the guidelines might have been selected.2,3 First, indeed, surgical mechanical thrombectomy could have been performed,8 but the surgical advice we received suggested otherwise. Second, catheter-directed thrombolytic therapy could have been administered directly into the right heart or pulmonary artery as previously described.9–12 This might have reduced the overall dose of rTPA, potentially reducing bleeding complications. This type of therapy was not discussed with the radiologists. Indeed, these alternatives were difficult to manage in our case because of the extreme emergency, wherein resuscitation from cardiac arrest, hemodynamic instability, and immediate difficulty transporting the patient to the thoracic center were all considerations. Hypothermia, which has been shown to reduce neurologic injury after pulseless electrical activity,13–15 was not performed because the patient was resuscitated after cardiac arrest in
I
ntracerebral hemorrhage (ICH) is a dreaded complication of thrombolytic therapy. Published guidelines related to use of antithrombotic and thrombolytic therapy for ischemic stroke1 report an incidence of symptomatic ICH after thrombolytic therapy in acute ischemic stroke of 7.3% compared with 5.9% in stroke trials. Additional guidelines recommend against thrombolysis for the treatment of stroke2 or pulmonary embolism3 after recent intracranial surgery. We describe successful thrombolytic treatment of massive bilateral pulmonary embolism occurring several hours after intracranial aneurysm clipping for a ruptured intracranial aneurysm. The local scientific and ethics committee of Comite d’Organisation et de Gestion de l’Anesthesie-Reanimation du Centre Hospitalier Universitaire de Montpellier approved the case report. We obtained patient permission to publish this case report.
CASE DESCRIPTION
A 71-year-old conscious and oriented man was admitted to the Montpellier University Hospital’s Stroke Center after 5 days of severe headache. The cerebral computed tomography (CT) scan revealed a right frontotemporal subarachnoid hemorrhage and a cerebral aneurysm of the right middle cerebral artery. Embolization of the aneurysm was scheduled 1 day later, but before it could be performed, the patient presented left hemiplegia with a Glasgow coma score of 7 (eyes, 2; verbal, 2; motor, 3). After tracheal intubation, repeat CT scan revealed a large ICH (Fisher grade 4) and he underwent emergent aneurysm clipping and i nsertion of external ventricular drain. From the Departments of *Intensive Care Unit (DAR C) and †Neurosurgery, Gui de Chauliac Hospital, University Hospital of Montpellier, Montpellier cedex, France. Accepted for publication March 07, 2013. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Audrey De Jong, MD, Unité de RéanimationDépartement d’Anesthésie-Réanimation “C”, University hospital. Chu de Montpellier Hopital Gui de Chauliac Hospital, 80 Ave. Augustin Fliche, 34295 Montpellier Cedex 5, France. Address e-mail to audreydejong@ hotmail.fr. Copyright © 2013 International Anesthesia Research Society DOI: 10.1097/ACC.0b013e318293d95b
October 15, 2013 • Volume 1 • Number 2
Four hours after admission to the intensive care unit (ICU), and while sedated with midazolam and fentanyl, he became hypoxemic and hemodynamically unstable. Cardiac ultrasound showed a dilated right ventricle, and lung CT scan with injection of contrast confirmed a massive pulmonary embolism. The coagulation data were normal with a prothrombin time (PT) at 12.3 seconds, activated partial thromboplastin time (APTT) at 24 seconds (ratio = 0.9), fibrinogen at 4.2 g/L, and 2,32,000/mm3 blood platelets. A cerebral CT scan was also performed (Fig. 1A). After discussion with the thoracic surgeon, surgical thrombectomy was not recommended. His hemodynamic state worsened quickly until cardiac arrest (pulseless electrical activity) occurred. Immediate resuscitation was instituted using 2 mg epinephrine and 1 minute of external cardiac compression (0 minutes of no flow and 1 minute of low flow) restored his arterial blood pressure to 110/60 mm Hg. Rescue fibrinolysis (alteplaserecombinant tissue plasminogen activator [rTPA]) was performed using an IV bolus of 10 mg followed by 40 mg in 30 minutes (patient weight: 80 kg, i.e., 0.6 mL/kg), through the right subclavian central venous access. Additional therapy using nonfractioned heparin and intermittent pneumatic compression was then started as a backup. In the evening, his PT was at 12.8 seconds and his APTT at 28.9 seconds (ratio = 1), with a fibrinogen at 4.4 g/L. The day after, under heparin therapy, the APTT was at 90.8 seconds (ratio = 2.7) and PT at 13.8 seconds. His hemodynamic variables were monitored by an echocardiography pulmonary artery catheter. Two hours after resuscitation, his cardiac output was 2 L/min. The urine output without diuretic therapy and the lactates (2 mmol/L) were normal. We used norepinephrine to maintain mean arterial blood pressure >65 mm Hg. Two days later, his cardiac output was 3.5 L/min with a gradient between the right ventricle and right atrium of 38 mm Hg, and a control CT scan showed worsening ICH and intraventricular bleeding (Fig. 1B). During his stay, the APTT was maintained between 70 and 90 to achieve a ratio between 2 and 3. The PT remains stable between 13.7 and 12.9 seconds. Regular CT scans were performed to monitor the intracerebral bleeding, and intracranial pressure was assessed every hour using an intraventricular catheter. His intracranial pressure remained low, and no cerebrospinal fluid was removed. cases-anesthesia-analgesia.org
31
When Benefits Outweigh the Risks...
A
Cerebral hemorrhage after clipping and before fibrinolysis
B
C
Cerebral hemorrhage recurrence two days after fibrinolysis
Cerebral hemorrhage disappearance one month after fibrinolysis
Figure 1. Brain computed tomography evolution before, 2 days after and 1 month after fibrinolysis. A, Cerebral hemorrhage after clipping and before fibrinolysis. B, Cerebral hemorrhage recurrence 2 days after fibrinolysis. C, Cerebral hemorrhage disappearance 1 month after fibrinolysis.
After 2 weeks of mechanical ventilation due to a persistent lung infection, the sedation was stopped and the patient regained consciousness 1 day later. His cardiac output was estimated at 5 L/min without pulmonary arterial hypertension. At day 28, his trachea was successfully extubated and cerebral tomography showed the disappearance of the intraventricular hemorrhage (Fig. 1C). At day 33, he was discharged from the ICU. He had a slight motor deficit in the left arm, was perfectly conscious, oriented, and did not require oxygen. One month later, he was discharged from the hospital and sent home, his blood anticoagulated with a vitamin K antagonist.
DISCUSSION
Massive pulmonary embolism leading to cardiac arrest a few hours after clipping of cerebral aneurysm is uncommon. We present a case of such a patient successfully treated by rescue fibrinolysis (alteplase-rTPA). Indeed, 1 month after the fibrinolysis, the patient was discharged from the ICU with his neurological state restored and good cardiac and pulmonary functions. A review related the use of alteplase for stroke beyond the guidelines4 and described 5 patients with an unruptured aneurysm who received IV alteplase for stroke.5 Two of them had a fatal ICH. During liver transplantation, Boone et al.6 reported the successful use of low-dose rTPA (0.5–4 mg) administration in 4 patients for the treatment of intracardiac thrombosis and pulmonary embolism. In our case, recent clipping of a ruptured aneurysm was an absolute contraindication to thrombolysis.3 However, in patients with massive and hemodynamically unstable pulmonary embolism, thrombolytic therapy has shown to rapidly improve their hemodynamics.3,7 Thus, in this case recognizing the risk of administering thrombolytic therapy, and faced with an immediate life-threatening situation, we chose to administer alteplase as a compassionate rescue
32 cases-anesthesia-analgesia.org
therapy. The dose of alteplase was 0.6 mL/kg, as advised in case of extremely severe pulmonary embolism.7 Alternative approaches other than we used and as suggested by the guidelines might have been selected.2,3 First, indeed, surgical mechanical thrombectomy could have been performed,8 but the surgical advice we received suggested otherwise. Second, catheter-directed thrombolytic therapy could have been administered directly into the right heart or pulmonary artery as previously described.9–12 This might have reduced the overall dose of rTPA, potentially reducing bleeding complications. This type of therapy was not discussed with the radiologists. Indeed, these alternatives were difficult to manage in our case because of the extreme emergency, wherein resuscitation from cardiac arrest, hemodynamic instability, and immediate difficulty transporting the patient to the thoracic center were all considerations. Hypothermia, which has been shown to reduce neurologic injury after pulseless electrical activity,13–15 was not performed because the patient was resuscitated after cardiac arrest in
