Inactive large cerebral hemorrhage is not exacerbated by the adjustment of anticoagulation post open-heart surgery

Abstract

Optimal timing of open-heart surgery for the treatment of patients with cerebral hemorrhage remains controversial because systemic heparinization may lead to catastrophic bleeding. Several recent reports have shown that patients who undergo open-heart surgery .within a few weeks of cerebral hemorrhage have a much lower risk of exacerbated bleeding than previously considered. Herein, we report a case of left atrial myxoma and large hemorrhagic embolic stroke, which was successfully operated on with no exacerbation of cerebral hemorrhage. Careful assessment of time-course changes in cerebral hemorrhage by neurological imaging and adjustment of anticoagulation can help prevent the exacerbation of postoperative cerebral hemorrhage and neurological deterioration.

<Learning objective: Evaluation of hemorrhagic activity is equally or more important than hemorrhagic size to prevent postoperative hemorrhagic deterioration in patients with preoperative cerebral hemorrhage. Careful assessment of time-course changes in cerebral hemorrhage by neurological imaging and adjustment of anticoagulation can help prevent the exacerbation of postoperative cerebral hemorrhage and neurological deterioration. Early open-heart surgery can be performed if the hemorrhage is judged as inactive, even if it is large.>

Introduction

Cerebral hemorrhage is often complicated by infective endocarditis (IE) [1] and rarely by Chen et al. [2]. Optimal timing of open-heart surgery in treating patients with cerebral hemorrhage remains controversial because systemic heparinization may cause catastrophic bleeding. The American Association for Thoracic Surgery consensus guidelines stated that in patients with recent intracranial hemorrhage, a delay of operation for 3 or more weeks is reasonable [3]; however, several reports have shown a much lower risk than previous reports, even in IE patients who underwent open-heart surgery within a few weeks after cerebral hemorrhage, if the hemorrhagic lesion was small [4,5]. Herein, we present a case of no exacerbation of postoperative cerebral hemorrhage by the adjustment of anticoagulation in a patient who underwent resection of left atrial myxoma with preoperative large cerebral hemorrhage presenting a slight cerebral mid-line shift.

Case report

A 73-year-old woman with no significant medical history developed left hemiplegia and aphasia. Upon arrival at a local hospital, her consciousness level was normal, with a Glasgow Coma Scale score of E4V5M5 and a modified Rankin scale score of 1. Electrocardiography showed sinus rhythm, and her heart rate was 70 beats per minute. Brain computed tomography (CT) showed a large cerebral hemorrhage in the right frontal lobe (40 × 40 mm) surrounded by edema, with a slight mid-line shift (Fig. 1A). Brain magnetic resonance imaging (MRI) was performed to diagnose the cerebral hemorrhage as hemorrhagic stroke (Fig. 2A). On day 2, brain CT revealed no cerebral hemorrhage progression (38 × 39 mm) (Fig. 1B), but diffusion-weighted brain MRI showed a new cerebral infarction in the left parietal lobe (Fig. 2B). Transthoracic echocardiography displayed a mobile mass (46 × 21 mm) in the left atrium. The patient was then transferred to our institute for surgical treatment. Her consciousness level was normal and cognitive function was preserved. The mass moved back and forth between the left atrium and ventricle and was about to get stuck in the mitral valve (Online Video 1). Brain CT showed no progression of hemorrhagic stroke and no new cerebral hemorrhage (Fig. 1C), as confirmed by experienced neurologists. Therefore, surgical resection was acceptable while preventing aggravation of hemorrhagic stroke; subsequently, emergency surgery was performed. To shorten the anticoagulation time, we approached through a median full sternotomy. During extracorporeal circulation, anticoagulation was adjusted to reduce cerebral hemorrhage risk: low-dose heparin (200 IU/kg) and nafamostat mesilate (0.5 mg/kg/h). The diatomaceous earth activated clotting time (ACT) was maintained at >400 s (Fig. 3). The left atrial mass was located at the atrial septal wall, attached by a thin stalk. The mass comprised yellow-greenish jelly-like fragile material and was completely resected en bloc. The aortic cross-clamping arrest, cardiopulmonary bypass, and operation times were 31, 89, and 185 min, respectively. No thrombus was detected in the artificial heart–lung circuit. Postoperative brain CT revealed no aggravation or new cerebral hemorrhage (Fig. 1D). The patient awoke without any new neurological deficits 2 days postoperatively. Brain MRI acquired 10 days postoperatively revealed no new cerebral infarction or hemorrhage (Fig. 2C). The mass was diagnosed as myxoma by pathological examination. The patient was transferred to another hospital for stroke rehabilitation 28 days postoperatively. Approval for publication was obtained from the patient and from our Institutional Review Board.

Fig. 1.

Series of brain computed tomography (CT) images. (A) Brain CT obtained on the day of onset. Large subcortical cerebral hemorrhage (40 × 40 mm) at the right-front cephalic fold, surrounded by edema and a slight mid-line shift. (B) Brain CT obtained on the day after onset. No progression of cerebral hemorrhage (38 × 39 mm). (C) Brain CT obtained preoperatively. No remarkable size change or new onset of cerebral hemorrhage (33 × 40 mm). (D) Brain CT obtained immediately postoperatively. No aggravation of cerebral hemorrhage (33 × 39 mm). (For interpretation of the references to color in this figure, the reader is referred to the web version of this article.).

Fig. 2.

Series of brain magnetic resonance (MR) images. (A) Axial T2-flair MR image obtained on the day of onset shows hemorrhagic stroke (40 × 40 mm), surrounded by edema. (B) Axial diffusion-weighted image obtained preoperatively shows a new cerebral infarction lesion in the left lateral ventricle (arrow). (C) Axial T2-weighted flair image obtained 10 days postoperatively reveals no new cerebral infarction or hemorrhage. The right cerebral infarction size remained unchanged compared with the preoperative size.

Fig. 3.

Intraoperative trend of diatomaceous earth and kaolin-measured ACT.ACT, activated coagulation time; CPB, cardiopulmonary bypass.The mass moving back and forth between the left atrium and left ventricle.

Discussion

For preoperative cerebral hemorrhage, early surgery using cardiopulmonary bypass has a risk of exacerbation of cerebral hemorrhage. Therefore, the timing of surgical treatment for such patients remains controversial. Yoshioka et al. showed that neither neurological deterioration nor exacerbation of hemorrhagic lesions occurred among all patients with preoperative intracranial hemorrhage who underwent valve surgery within 2 weeks of hemorrhagic onset [4]. Kim et al. demonstrated that early surgery (within 1 week) was not associated with in-hospital mortality and 1-year adverse outcomes in IE patients with hemorrhagic complications [5]. They also indicated that patients with ≤2 cm emboli and hemorrhage may undergo surgery within 7 days. In the present case, the hemorrhagic size was approximately 4 cm, but no neurological deterioration and exacerbation of cerebral hemorrhage occurred, although surgery was performed 2 days after hemorrhagic onset. We believe that evaluation of “hemorrhagic activity” is equally or more important than “hemorrhagic size” to prevent postoperative hemorrhagic exacerbation. A recurrent hemorrhage is unlikely to develop because myxoma is a tumor and not an inflammatory disease like IE, which causes microbleeds or mycotic aneurysm-causing hemorrhage [6]. The present cerebral hemorrhage had not enlarged during the time course, as assessed by CT. Instead, a new embolic stroke developed, as assessed by MRI. Therefore, early surgery is justified because the hemorrhage can be judged inactive and may develop further embolic events when surgery is delayed [6].

To reduce the risk of devastating cerebral hemorrhage during cardiopulmonary bypass, the management of anticoagulation is crucial. The combination of low-dose heparin and nafamostat mesilate is effective against neurological deterioration, new occurrence of intracranial hemorrhage, and clot formation in patients with acute ischemic or hemorrhagic stroke [7,8]. We used 200 IU/kg of low-dose heparin (our normal dosage for cardiopulmonary bypass is 300 IU/kg) to adjust kaolin-measured ACT between 350 and 400 s, which reflects heparin activity alone in the blood under the combined use of nafamostat mesilate [7]. Moreover, nafamostat mesilate was added to obtain a diatomaceous earth ACT >400 s. Our dosage of anticoagulants was greater than previously described [7,8]: when we used a single low-dose heparin (150 IU/kg or 200 IU/kg with target ACT of approximately 350 s), clot formation occurred on the prosthetic valve or cardiopulmonary bypass circuit intraoperatively. The use of nafamostat mesilate can help avoid recurrent intracranial hemorrhage by not activating fibrinolysis and prevent clot formation that can occur with low-dose heparin administration alone.

In conclusion, early open-heart surgery can be performed if the hemorrhage is judged as inactive, even if it is large. Adjustment of anticoagulation can help prevent the exacerbation of postoperative cerebral hemorrhage.

Declaration of Competing Interest

The authors declare that there is no conflict of interest.