Perioperative Management of a Patient with Severe Factor V Deficiency Presenting with Chronic Subdural Hematoma: A Clinical Report.

BACKGROUND: Severe factor V deficiency is an extremely rare coagulation disorder. Patients with factor V activity <5% usually become symptomatic in early childhood. CASE DESCRIPTION: We report the case of an 82-year-old woman with incidentally diagnosed severe factor V deficiency, who developed a symptomatic chronic subdural hematoma, requiring burr hole craniostomy. Successful management was achieved by a multidisciplinary approach. Preoperatively, factor V activity was increased from 2% to 50% by administration of 25 mL/kg body weight of fresh frozen plasma over 30 minutes under close cardiopulmonary monitoring in the intensive care unit. Straight afterward, the patient was transferred to the operating room where surgery was performed under general anesthesia. Burr hole craniostomy could be performed without perioperative complications. In the postoperative days, there was no relevant recurrence of the subdural hematoma in the follow-up computed tomography scans under frequent control of coagulation parameters. However, despite further transfusion of fresh frozen plasma, factor V activity did not increase >16%. The patient was discharged without any neurologic deficits. In a hemostaseologic follow-up 2 months after surgery, factor V activity <1% was confirmed with evidence of a factor V inhibitor in the modified Bethesda assay. Most likely, the patient suffered from an acquired form of factor V deficiency with preformed antibodies that had been boosted by the initial treatment with fresh frozen plasma. CONCLUSIONS: We conclude that in this rare bleeding disorder, intracranial surgery was successfully managed because of a thoroughly planned perioperative therapeutic strategy. However, if there is time prior to surgery, a full checkup of the bleeding disorder is advisable.

Interleukin 6 in the Cerebrospinal Fluid as a Biomarker for Onset of Vasospasm and Ventriculitis After Severe Subarachnoid Hemorrhage.

OBJECTIVE: The aim of the study was to investigate the diagnostic potential of interleukin 6 (IL-6) and other soluble biomarkers in serum and cerebrospinal fluid (CSF) for early diagnosis of cerebral vasospasm (cVSSAH) and external ventricular drain-associated ventriculitis (VCSAH) and to separate these conditions from aneurysmal subarachnoid hemorrhage (aSAH) without further complication (SAHw/o/c). METHODS: The concentrations of serum biomarkers and markers in the CSF were collected in 63 consecutive patients with aSAH and external ventricular drainage. Arithmetical means and standard deviations, area under the curve (AUC), cutoff values (C-OFF), sensitivity (SE), and specificity (SP) were calculated for markers and their correlation with SAHw/o/c, cVSSAH, and VCSAH. RESULTS: Clinical courses included 27 patients with cVSSAH, 17 with VCSAH, and 19 with SAHw/o/c. Mean ± standard deviationCSFIL-6 values were 7588 ± 4580 pg/mL at onset of VCSAH and 4102 ± 4970 pg/mL for cVSSAH and higher than 234 ± 239 pg/mL in SAHw/o/c (P < 0.001). CSFIL-6 showed excellent diagnostic potential for differing between VCSAH and SAHw/o/c (AUC, 1.00; C-OFF, 707; SE, 100%; SP, 100%), and a moderate diagnostic potential for differing VCSAH from cVSSAH (AUC, 0.757; C-OFF, 3100 pg/Ml; SE, 86.7%; SP, 70.6%). The concentration of CSFIL-6 within the cVSSAH group was significantly increased compared with SAHw/o/c (AUC, 0.937; C-OFF, 530 pg/mL; SE, 87.5%; SP, 91.7%). CONCLUSIONS: CSFIL-6 is increased after aSAH in patients with cVSSAH or VCSAH. Patients with a CSFIL-6 level higher than a C-OFF of 3100 pg/mL have an increased likelihood for VCSAH; patients with CSFIL-6 levels between 530 and 3100 pg/mL have an increased posttest probability for cVSSAH.

Cerebrospinal fluid penetration of meropenem in neurocritical care patients with proven or suspected ventriculitis: a prospective observational study.

BACKGROUND: Ventriculitis is a complication of temporary intraventricular drains. The limited penetration of meropenem into the cerebrospinal fluid (CSF) is well known. However, ventricular CSF pharmacokinetic data in patients with ventriculitis are lacking. The aim of this study was to evaluate meropenem pharmacokinetics in the serum and CSF of neurocritical care patients with proven or suspected ventriculitis. METHODS: We conducted an observational pharmacokinetic study of neurocritical care patients with proven or suspected ventriculitis receiving meropenem. Multiple blood and CSF samples were taken and were described using nonparametric pharmacokinetic modelling with Pmetrics. RESULTS: In total, 21 patients (median age 52 years, median weight 76 kg) were included. The median (range) of peak and trough concentrations in serum were 20.16 (4.40-69.00) mg/L and 2.54 (0.00-31.40) mg/L, respectively. The corresponding peak and trough concentrations in CSF were 1.20 (0.00-6.20) mg/L and 1.28 (0.00-4.10) mg/L, respectively, with a median CSF/serum ratio (range) of 0.09 (0.03-0.16). Median creatinine clearance ranged from 60.7 to 217.6 ml/minute (median 122.5 ml/minute). A three-compartment linear population pharmacokinetic model was most appropriate. No covariate relationships could be supported for any of the model parameters. Meropenem demonstrated poor penetration into CSF, with a median CSF/serum ratio of 9 % and high interindividual pharmacokinetic variability. CONCLUSIONS: Administration of higher-than-standard doses of meropenem and therapeutic drug monitoring in both serum and CSF should be considered to individualise meropenem dosing in neurocritical care patients with ventriculitis.

Lymphocyte subsets and the role of TH1/TH2 balance in stressed chronic pain patients.

BACKGROUND: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. METHODS: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. RESULTS: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. CONCLUSIONS: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients.