Favorable outcome of rivaroxaban-associated intracerebral hemorrhage reversed by 4-factor prothrombin complex concentrate: impact on thrombin generation.

The management of life-threatening bleeding associated with rivaroxaban remains a challenge for physicians due to the lack of evidence about clinically effective options for anticoagulation reversal. We report a favorable outcome in a patient receiving rivaroxaban prophylaxis, who developed a spontaneous subdural hematoma treated by a surgical evacuation and administration of 4-factor prothrombin complex concentrate. Classical coagulation variables were associated with impaired thrombin generation. Reversal with prothrombin complex concentrates improved all thrombin generation measures. Thrombin generation tests may be suitable for assessing the clinical utility of reversal drugs on rivaroxaban-induced coagulopathy.

Outcome and complications of chronically implanted subdural electrodes for the treatment of medically resistant epilepsy.

BACKGROUND: Surgery for medically resistant epilepsy is safe and effective. However, when noninvasive techniques are insufficient, then consideration is given to invasive electrocorticography (EcoG). OBJECTIVE: The aim of the study was to analyze results and complications of subdural electrodes placement in the treatment of intractable epilepsy. METHODS: Ninety-one consecutive patients who underwent placement of subdural electrodes (1999-2010) were considered for this study. All patients underwent a standardized pre-operative evaluation. Invasive subdural electrode placement was considered when there were inadequate ictal recordings, there was discordance between EEG and neuroimaging or the epileptogenic zone was localized near eloquent cortex. RESULTS: Resective epilepsy surgery was performed in 70/91 patients (76.9%). Twenty-four out of seventy (34.3%) who underwent surgical resection were seizure-free (CL-I) at last follow-up. A statistical evaluation revealed a very strong trend for patients with positive lesional pre-operative MRI to have improved outcomes compared to normal brain MRI population (p=.028). There were 10 surgical related complications (11%), but no mortality or permanent morbidity. Statistical analysis demonstrated that placement of a subdural grid in any combination was statistically significant (p=.01) for surgical complications. CONCLUSIONS: Invasive monitoring is a useful and necessary technique for the surgical treatment of intractable epilepsy. Careful surveillance is required during the monitoring period especially when the patient has undergone large subdural grid placement. A good working hypothesis can minimize complications and achieve better outcomes.

An evidence-based approach to managing the anticoagulated patient in the emergency department.

You start another busy shift with a double row of charts waiting to be seen. Your first patient is an elderly man who fell 1 hour prior to presentation. He did not lose consciousness, but he was dazed for a few minutes. He complains of a mild headache but denies any neck pain. He takes warfarin for valvular heart disease. He looks good and has no focal neurological complaints. His mental status is normal, he has a negative head CT scan, and his INR is 3.9. His family wants to take him home, which would help relieve some of the congestion in the ED, but you wonder what would be best. To observe and repeat imaging? Reverse his anticoagulation? Change his dosing regimen of warfarin? In the next room, you quickly evaluate a 51-year-old obese woman with nonspecific back and abdominal pain that started 24 hours before and has slowly progressed to become intolerable. She denies fever, chills, nausea, or vomiting. She is on the last day of a 5-day course of ciprofloxacin for a UTI. She takes warfarin for a pulmonary embolus that occurred 2 months prior. Her hematocrit is mildly decreased, and her white blood count is normal; however, the INR is 6.8. You wonder if her abdominal pain is related to the UTI, or if it could be somehow related to the prolonged INR. In fact, you wonder why her INR is so prolonged...

Sequential occurrence of life-threatening hypokalemia and rebound hyperkalemia associated with barbiturate coma therapy.

OBJECTIVE: To report a sequential occurrence of life-threatening hypokalemia and rebound hyperkalemia following barbiturate coma therapy. CASE HISTORY: A 53-year-old man was admitted to the division of nephrology due to sudden development of severe hypokalemia. The patient had been treated following a clinical diagnosis of traumatic subarachnoid hemorrhage and subdural hematoma. Barbiturate coma therapy had been performed on this patient. He developed fatal hypokalemia 10 hours after the start of thiopental administration which did not respond to potassium supplementation. The lowest potassium level following barbiturate coma therapy was 1.0 mmol/l. Severe bradycardia and cardiac arrest developed, which necessitated cardiac massage and treatment with epinephrine and atropine. He recovered from cardiac arrest. When thiopental infusion was suddenly stopped, the potassium level increased to 8.9 mmol/l, which required quick administration of calcium gluconate and infusion of glucose solution mixed with regular insulin. Despite such management, he developed asystole. After direct current cardioversion and emergency hemodialysis, he recovered from cardiac arrest and his serum potassium level was stabilized. CONCLUSION: We recommend that clinicians must be aware of the potential occurrence of severe hypokalemia, which is rare but fatal, following barbiturate coma therapy. Rebound hyperkalemia, which is fatal, may also occur following cessation of thiopental infusion. Clinicians should also be aware of this potential complication. Further studies are needed to elucidate the precise mechanism of this clinical event.

Selective intermediate-/small-conductance calcium-activated potassium channel (KCNN4) blockers are potent and effective therapeutics in experimental brain oedema and traumatic brain injury caused by acute subdural haematoma.

Early deterioration and death after brain injury is often the result of oedema in the injured and peri-lesional tissue. So far, no pharmacotherapy is available that exhibits significant brain oedema-reducing efficacy in patients. We selected two low molecular weight compounds from different chemical classes, a triazole (1-[(2-chlorophenyl)diphenylmethyl]-1,2,3-triazole) and a cyclohexadiene (methyl 4-[4-chloro-3-(trifluoromethyl)phenyl]-6-methyl-3-oxo-1,4,7-tetrahydroisobenzofuran-5-carboxylate) to characterize their pharmacological properties on KCNN4 channels (intermediate/small conductance calcium-activated potassium channel, subfamily N, member 4) in vitro as well as in vivo. In vitro we replaced potassium by rubidium (Rb+) and determined Rb+ fluxes evoked by 10 micro m of the calcium ionophore A23187 on C6BU1 rat glioma cells. Compared with known KCNN4 blockers, such as clotrimazole (IC50=360 +/- 12 nm) and charybdotoxin (IC50=3.3 +/- 1.9 nm), the triazole and cyclohexadiene were considerably more potent than clotrimazole and displayed similar potencies (IC50=12.1 +/- 8.8 and 13.3 +/- 4.7 nm, respectively). In the rat acute subdural haematoma model, both the triazole and cyclohexadiene displayed reduction of brain water content (-26% at 0.3 mg/kg and -24% at 0.01 mg/kg) and reduction of the intracranial pressure (-46% at 0.1 mg/kg and -60% at 0.003 mg/kg) after 24 h when administered as a 4-h infusion immediately after brain injury. When infarct volumes were determined after 7 days, the triazole as well as the cyclohexadiene displayed strong neuroprotective efficacy (-52% infarct volume reduction at 1.2 mg/kg and -43% at 0.04 mg/kg, respectively). It is concluded that blockade of KCNN4 channels is a new pharmacological approach to attenuate acute brain damage caused by traumatic brain injury.

Assessment of prognostic factors in severe traumatic brain injury patients treated by mild therapeutic cerebral hypothermia therapy.

This study analyzed the predictable factors of outcome such as neuro-parameters and systemic complications to elucidate the indications for therapeutic hypothermia. In our institute, 35 patients with severe head injury (Glasgow Coma Scale 3-7) were treated with mild hypothermia therapy (33 degrees-35 degrees C). Twenty-two of these 35 patients underwent complete neuromonitoring and outcome assessments by Glasgow Outcome Scale (GOS) at three months after injury. GOS of hypothermia group was significantly better than another patient group which was treated without mild hypothermia therapy. The hypothermia group was divided into two groups: good outcome (GOOD) (good recovery or moderate disability; n = 9, 40.9%) and poor outcome (POOR) (severe disability, vegetative state, or death; n = 13, 59.1%). The mean age (mean 30.2 years, range 9-46) was significantly lower in GOOD than in POOR (mean 45.2 years, range 17-62). Patients aged over 50 years had poor outcome. CPP was significantly higher in GOOD during hypothermia. All patients with thrombocytopenia had poor outcome. Hypothermia therapy can improve outcome in patients with traumatic brain injury who are younger than 50 years old, without severe brain damage, and if improvement of cerebral perfusion is expected. Systemic complications must be prevented as far as possible by combination with other therapies.

[Clinical study on Zhuyu Xiaozhong mixture combined with stereotaxic drainage in treating hypertensive cerebral hemorrhage].

OBJECTIVE: To explore the effective method of integrated traditional Chinese and western medicine (TCM-WM) therapy in treating hypertensive cerebral hemorrhage (HCH). METHODS: Sixty-one HCH patients were randomly divided into two groups: the treated group (group A, 31 cases) and the control group (group B, 30 cases), the former group was treated with stereotaxic drainage and orally taken Zhuyu Xiaozhong mixture (ZYXZM), and the latter group with stereotaxic drainage alone. RESULTS: The total effective rate of group A was 83.9%, significantly higher than that of group B (60.0%, P < 0.05). In comparing the two groups, the neurological function recovery, the quality of life and the hematoma absorption in group A were significantly better than those of group B (P < 0.05). CONCLUSION: ZYXZM combined with stereotaxic drainage is effective in treating HCH. It could promote the neurological function recovery and improve the quality of life as well.

[Anesthetic management of patients undergoing irrigation and drainage of chronic subdural hematoma--retrospective analysis of analgesia and sedation under locoregional anesthesia].

We retrospectively investigated the relationship between intraoperative hemodynamic variability and variables including patient background, anesthetic profile, and operative profile in 108 patients undergoing irrigation and drainage of chronic subdural hematoma under locoregional anesthesia. Patients were divided into two groups according to the degree of changes in mean arterial blood pressure (MAP) and heart rate (HR) during operation. Group A (n = 66) had MAP and HR changes < 20%, and Group B (n = 42) had MAP or HR changes > or = 20% of preoperative baseline values. Age was significantly higher in group B than Group A (mean +/- SD; 70 +/- 12 vs. 62 +/- 14 years, P < 0.01). In respect to additional anesthetic agents used (none; no additional anesthetic agents, enough; pentazocine > or = 0.3 mg.kg-1 and droperidol > or = 0.05 mg.kg-1, pentazocine > or = 0.5 mg.kg-1 or droperidol > or = 0.15 mg.kg-1, little; less than "enough"), ratio of "little" administered in Group B was significantly higher than that in Group A (64.3% vs. 37.9%, P < 0.05). These findings suggest that intraoperative hemodynamic variability under locoregional anesthesia in patients with chronic subdural hematoma is associated with age and insufficient use of hypnotic and/or analgesic agents.

Acute subdural hemorrhage complicating embolization of a cerebral arteriovenous malformation.

We present a case of a young adult in whom acute subdural hemorrhage developed immediately after embolization of a cerebral arteriovenous malformation with glue. Inadvertent venous outlet obstruction with glue was implicated in the production of the hemorrhage. Possible mechanisms of spread of blood to the subdural space are discussed. Awareness of the possibility of iatrogenic subdural hemorrhage is necessary before undertaking embolization procedures.