Therapeutic anticoagulation after craniotomies: is the risk for secondary hemorrhage overestimated?

OBJECTIVE: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are major causes of postoperative morbidity and mortality in surgery. However, there is neither a standardized protocol for perioperative prevention of DVT or PE in neurosurgery nor a consensus concerning the management of postoperative DVT or PE after craniotomy in the early postoperative course. METHODS: We retrospectively analyzed management and complications in a group of patients with postoperative DVT or PE after craniotomy between 2006 and 2011 to estimate the risk of secondary hemorrhage under therapeutic anticoagulation. The interval between time of craniotomy and diagnosis of PE or DVT, administered anticoagulation, and the appearance of a clinically relevant secondary hemorrhage were analyzed. RESULTS: Forty-two patients met the given criteria. Indications for surgery were intracranial tumors (n = 33), aneurysms (n = 5), and hematomas (n = 4). PE or DVT was observed between the first and the 28th postoperative day (median, fifth postoperative day). Therapeutic anticoagulation was performed with enoxaparin or heparin (according to partial thromboplastin time levels). Full heparinization was applied in 30 patients between the second and the 30th postoperative day (median, 12th postoperative day). None of these patients developed a secondary hemorrhage. CONCLUSION: The documented differences in the anticoagulative drug used, the drug's dosage, and the start of medication reflect the lack of a standardized protocol concerning the treatment of postoperative PE or DVT after craniotomy. A more aggressive management regarding the application of anticoagulative drugs after craniotomy may be justified considering the absence of clinically relevant hemorrhages in this study and the life-threatening potential of perioperative DVT or PE.

Neuroprotective efficacy of prophylactic enteral and parenteral nimodipine treatment in vestibular schwannoma surgery: a comparative study.

UNLABELLED: BACKGROUND AND STUDY AIMS/OBJECT: Oral nimodipine improves neurologic outcome after aneurysmal subarachnoid hemorrhage. In addition, the neuroprotective efficacy of nimodipine has been revealed following skull base, laryngeal, and maxillofacial surgery. Pharmacokinetic investigations showed nimodipine to reach higher serum levels following parenteral versus enteral administration. Furthermore, a correlation between nimodipine levels in serum, cerebrospinal fluid, and nerve tissue could be quantified. These observations raise the question whether the proven neuroprotective effect of nimodipine is related to its serum level. PATIENTS/MATERIAL AND METHODS: A consecutive series of 37 patients with vestibular schwannoma treated with nimodipine from the day before surgery until the seventh postoperative day was analyzed retrospectively. Both groups received standard dosages for enteral (n = 17) and parenteral (n = 20) nimodipine medication. Nimodipine levels were measured in pre- and postoperative serum and cerebrospinal fluid samples. Cochlear and facial nerve functions were documented before surgery, in the early postoperative course, and 1 year after surgery. RESULTS: Facial nerve outcome was significantly better in the group with parenteral nimodipine medication (p = 0.038). Logistical regression analysis revealed a seven times smaller risk for a deterioration of facial nerve function in the group with parenteral treatment. There was no difference in hearing preservation between both groups despite tumor size tending to be larger in the parenteral group. Intraoperative (p = 0.004), postoperative (p = 0.001), and serum and cerebrospinal fluid (p = 0.024) nimodipine levels were significantly higher following parenteral administration as compared with enteral administration. Both groups were comparable regarding tumor size and extent of resection. CONCLUSIONS: These results support a dependency of nimodipine's neuroprotective efficacy on its serum levels. Parenteral nimodipine treatment produces higher serum levels and has a higher neuroprotective potency in vestibular schwannoma surgery compared with enteral treatment.

Enteral or parenteral nimodipine treatment: a comparative pharmacokinetic study.

UNLABELLED: BACKGROUND AND STUDY AIMS/OBJECT: Oral nimodipine is recommended to reduce poor outcome related to aneurysmal subarachnoid hemorrhage (SAH). In addition, animal experiments and clinical trails revealed a beneficial effect of enteral and parenteral nimodipine for the regeneration of cranial nerves following skull base, laryngeal, and maxillofacial surgery. Despite these findings there is a lack of pharmacokinetic data in the literature, especially concerning its distribution in nerve tissue. PATIENTS/MATERIAL AND METHODS: Samples were taken from a consecutive series of 57 patients suffering from skull base lesions and treated with nimodipine prophylaxis from the day before surgery until the seventh postoperative day. Both groups received standard dosages for enteral (n = 25) and parenteral (n = 32) nimodipine . Nimodipine levels were measured in serum, cerebrospinal fluid (CSF), and tissue samples, including vestibular nerves. RESULTS: Nimodipine levels were significantly higher following parenteral as compared with enteral administration for intraoperative serum (p < 0.001), intraoperative CSF (p < 0.001), tumor tissues (p = 0.01), and postoperative serum (p < 0.001). In addition, nimodipine was significantly more frequently detected in nerve tissue following parenteral administration (Fisher's exact test, p = 0.015). CONCLUSIONS: From a pharmacokinetic point of view, parenteral nimodipine medication leads to higher levels in serum and CSF. Furthermore, traces are more frequently found in nerve tissue following parenteral as compared with enteral nimodipine administration, at least in the early course.

D-dimer plasma level: a reliable marker for venous thromboembolism after elective craniotomy.

OBJECT: The incidence of deep venous thrombosis (DVT) after craniotomy is reported to be as high as 50%. In outpatients, D-dimer levels of more than 0.5 mg/L indicate venous thromboembolism (VTE, which subsumes DVT and pulmonary embolism [PE]) with a sensitivity of 99.4% and a specificity of 38.2%. However, D-dimer levels are believed to be unreliable in postoperative patients. The authors undertook the present study to test the hypothesis that D-dimer levels would be systematically raised in a postoperative population and to define a feasible threshold for identification of VTE. METHODS: Doppler ultrasonography of the lower extremity was performed pre- and postoperatively to evaluate for DVT in 101 patients who underwent elective craniotomy. D-dimer levels were assessed preoperatively and on the 3rd, 7th, and 10th days after surgery. Statistical analysis was carried out to define a feasible threshold for D-dimer levels. RESULTS: D-dimer plasma levels were found to be systematically raised postoperatively, and they differed between patients with and without VTE in a highly significant way. On the 3rd day after surgery, D-dimer levels of more than 2 mg/L indicated VTE with a sensitivity of 95.3% and a specificity of 74.1%, allowing for the definition of a feasible threshold. D-dimer levels of more than 4 mg/L were observed in all patients who had PE during the postoperative period (n = 9). Ventilation time and duration of surgery were identified as highly significant risk factors for the development of VTE. CONCLUSIONS: Using a threshold of 2 mg/L, D-dimer levels will indicate VTE with a high degree of sensitivity and specificity in patients who have undergone craniotomy. Pulmonary embolism seems to be indicated by even higher D-dimer levels. Given that the development of D-dimer plasma levels in the postoperative period follows a principle that can be predicted and that deviations from it indicate VTE, this principle might be applicable to other types of surgery.

Erectile dysfunction as rare side effect in the simultaneous intrathecal application of morphine and clonidine.

We report on the case of a 52-year-old man who presented with a history of chronic neuropathic pain treated with intrathecal application of morphine for many years. In spite of significant dose escalation, considerable pain relief had not been achieved. Ziconotide had been tried but not only did it not provide pain relief, but it also caused severe side effects in this patient. A combination of morphine and clonidine was delivered by a programmable pump, slowly increasing the clonidine rate over several weeks. For ease of transition and minimization of hospitalization, which was a special concern to this patient, combining clonidine and morphine was chosen over monotherapy with hydromorphone, with both possibilities being described as equal alternatives in the literature. Considerable pain relief was achieved during week 2 at a clonidine dose of 0.040 mg/d, thereby decreasing the visual analog score (VAS) from 10 to 4. Yet, after developing erectile dysfunction and relative hypotension soon after beginning clonidine treatment, the patient decided not to continue with the combined application of morphine and clonidine. Treatment was therefore switched back to the former monotherapy with morphine. Thereafter, erectile dysfunction disappeared and blood pressure returned to habitual high levels. Although common in systemic application, erectile dysfunction caused by the intrathecal application of clonidine has not been described yet in the literature. In this patient, this rare side effect decisively impaired life quality, subjectively outweighing the considerable pain relief which could be achieved after formerly inefficacious treatment. Further and prospective investigation might be needed to estimate the connection of erectile dysfunction to intrathecal application of clonidine.