Early prediction of ventricular peritoneal shunt dependency in aneurysmal subarachnoid haemorrhage patients by recurrent neural network-based machine learning using routine intensive care unit data.

Aneurysmal subarachnoid haemorrhage (aSAH) can lead to complications such as acute hydrocephalic congestion. Treatment of this acute condition often includes establishing an external ventricular drainage (EVD). However, chronic hydrocephalus develops in some patients, who then require placement of a permanent ventriculoperitoneal (VP) shunt. The aim of this study was to employ recurrent neural network (RNN)-based machine learning techniques to identify patients who require VP shunt placement at an early stage. This retrospective single-centre study included all patients who were diagnosed with aSAH and treated in the intensive care unit (ICU) between November 2010 and May 2020 (n = 602). More than 120 parameters were analysed, including routine neurocritical care data, vital signs and blood gas analyses. Various machine learning techniques, including RNNs and gradient boosting machines, were evaluated for their ability to predict VP shunt dependency. VP-shunt dependency could be predicted using an RNN after just one day of ICU stay, with an AUC-ROC of 0.77 (CI: 0.75-0.79). The accuracy of the prediction improved after four days of observation (Day 4: AUC-ROC 0.81, CI: 0.79-0.84). At that point, the accuracy of the prediction was 76% (CI: 75.98-83.09%), with a sensitivity of 85% (CI: 83-88%) and a specificity of 74% (CI: 71-78%). RNN-based machine learning has the potential to predict VP shunt dependency on Day 4 after ictus in aSAH patients using routine data collected in the ICU. The use of machine learning may allow early identification of patients with specific therapeutic needs and accelerate the execution of required procedures.

A recurrent machine learning model predicts intracranial hypertension in neurointensive care patients.

The evolution of intracranial pressure (ICP) of critically ill patients admitted to a neurointensive care unit (ICU) is difficult to predict. Besides the underlying disease and compromised intracranial space, ICP is affected by a multitude of factors, many of which are monitored on the ICU, but the complexity of the resulting patterns limits their clinical use. This paves the way for new machine learning techniques to assist clinical management of patients undergoing invasive ICP monitoring independent of the underlying disease. An institutional cohort (ICP-ICU) of patients with invasive ICP monitoring (n = 1346) was used to train recurrent machine learning models to predict the occurrence of ICP increases of ≥22 mmHg over a long (>2 h) time period in the upcoming hours. External validation was performed on patients undergoing invasive ICP measurement in two publicly available datasets [Medical Information Mart for Intensive Care (MIMIC, n = 998) and eICU Collaborative Research Database (n = 1634)]. Different distances (1-24 h) between prediction time point and upcoming critical phase were evaluated, demonstrating a decrease in performance but still robust AUC-ROC with larger distances (24 h AUC-ROC: ICP-ICU 0.826 ± 0.0071, MIMIC 0.836 ± 0.0063, eICU 0.779 ± 0.0046, 1 h AUC-ROC: ICP-ICU 0.982 ± 0.0008, MIMIC 0.965 ± 0.0010, eICU 0.941 ± 0.0025). The model operates on sparse hourly data and is stable in handling variable input lengths and missingness through its nature of recurrence and internal memory. Calculation of gradient-based feature importance revealed individual underlying decisions for our long short time memory-based model and thereby provided improved clinical interpretability. Recurrent machine learning models have the potential to be an effective tool for the prediction of ICP increases with high translational potential.

Cerebrospinal fluid penetration of fosfomycin in patients with ventriculitis: an observational study.

BACKGROUND: For treatment of ventriculitis, vancomycin and meropenem are frequently used as empiric treatment but cerebrospinal fluid (CSF) penetration is highly variable and may result in subtherapeutic concentrations. Fosfomycin has been suggested for combination antibiotic therapy, but data are sparse, so far. Therefore, we studied CSF penetration of fosfomycin in ventriculitis. METHODS: Adult patients receiving a continuous infusion of fosfomycin (1 g/h) for the treatment of ventriculitis were included. Routine therapeutic drug monitoring (TDM) of fosfomycin in serum and CSF was performed with subsequent dose adaptions. Demographic and routine laboratory data including serum and CSF concentrations for fosfomycin were collected. Antibiotic CSF penetration ratio as well as basic pharmacokinetic parameters were investigated. RESULTS: Seventeen patients with 43 CSF/serum pairs were included. Median fosfomycin serum concentration was 200 [159-289] mg/L and the CSF concentration 99 [66-144] mg/L. Considering only the first measurements in each patient before a possible dose adaption, serum and CSF concentrations were 209 [163-438] mg/L and 104 [65-269] mg/L. Median CSF penetration was 46 [36-59]% resulting in 98% of CSF levels above the susceptibility breakpoint of 32 mg/L. CONCLUSION: Penetration of fosfomycin into the CSF is high, reliably leading to appropriate concentrations for the treatment of gram positive and negative bacteria. Moreover, continuous administration of fosfomycin appears to be a reasonable approach for antibiotic combination therapy in patients suffering from ventriculitis. Further studies are needed to evaluate the impact on outcome parameters.

Acute low-pressure hydrocephalus in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Acute and chronic hydrocephalus are common pathologies after aneurysmal subarachnoid hemorrhage (SAH). Generally, the presence of acute hydrocephalus is associated with elevated intracranial pressure (ICP) treated with a ventricular drain. Subsequently, however, pronounced hydrocephalus without elevated ICP may develop in some patients with SAH in the postacute phase. This is described as acute low-pressure hydrocephalus (aLPH), and there are very limited data in the literature of this pathology. The aim of this study was to evaluate the rate of and factors associated with aLPH and describe its clinical course. METHODS: In this retrospective single-center cohort study, the frequency and clinical characteristics of SAH-associated aLPH were investigated. Acute LPH was defined as an increase in ventricular size as measured by the Evans index, ICP within the normal range (< 5 mm Hg) at the time of ventricular enlargement, and timely neurological improvement after indwelling ventricular CSF drainage with negative pressure up to 5 cm H2O below normal level. Demographic and SAH-specific factors in patients with SAH treated using an external ventricular drain were extracted from the electronic medical chart and further analyzed. RESULTS: From November 2010 to May 2020, 15 (3.7.%) of 406 patients with SAH fulfilled the criteria for aLPH. Acute LPH was diagnosed after an average of 13.1 ± 7.7 days. The presence of IVH and its extension were associated with the occurrence of aLPH. After undergoing the transient phase of aLPH, these patients subsequently developed a chronic, typical malresorptive hydrocephalus requiring a ventriculoperitoneal shunt more often (66.7% vs 17.4%, p < 0.001) and stayed longer in the intensive care unit (27 vs 20.5 days, p = 0.043) and in the hospital (36.4 vs 26.3 days, p = 0.004). CONCLUSIONS: Acute LPH is a rare pathology in patients with SAH and negatively impacts the clinical course. It should be especially considered in patients with a lack of neurological improvement, an increase in ventricular width, and normal ICP values, so that forced CSF drainage is implemented.

Terson Syndrome in Patients with Aneurysmal Subarachnoid Hemorrhage: A 10-Year Single-Center Experience.

BACKGROUND: Terson syndrome (TS), an intraocular hemorrhage associated with aneurysmal subarachnoid hemorrhage (aSAH), occurs in up to 46% of all patients with subarachnoid hemorrhage. Despite its high incidence, TS is underrepresented in the literature, and patients with aSAH are sometimes not systematically evaluated for the presence of TS in clinical practice. This work aims to raise awareness of TS, reevaluate previous scientific findings, describe risk factors associated with the occurrence of TS, and present our local diagnostic and treatment concept. METHODS: All patients with aSAH treated at our institution between October 2010 and May 2020 were included in this retrospective study. The frequency of ophthalmological screening by indirect funduscopy, as well as the results, was investigated. In addition, the collection and statistical analysis of epidemiological and clinical data was performed using χ2, Kruskal-Wallis, and analysis of variance testing; multivariate regression; and receiver operating characteristic analysis. The significance level was set at p < 0.05. RESULTS: A total of 617 patients were treated for aSAH in our institution. Of these, 367 patients (59.5%) were ophthalmologically examined for the presence of TS. The rate of TS in the examined patients was 21.3% (n = 78). Patients with TS had significantly higher Fisher and World Federation of Neurosurgical Societies (WFNS) scores (p < 0.0001). Regression analyses showed WFNS grade (p = 0.003) and the occurrence of seizures (p = 0.002) as independent predictors of TS, as did receiver operating characteristic analyses, which had a significant area under the curve of 0.66 for the combination of WFNS grade and seizures. For 12 (15.4%) patients, the TS had to be surgically treated by pars plana vitrectomy in a total of 14 eyes, which resulted in significant improvement of visual function in all patients: mean preoperative best-corrected visual acuity was 0.03 (± 0.08) versus 0.76 (± 0.21) postoperatively (p < 0.001). CONCLUSIONS: TS is a common complication in patients with aSAH, affecting approximately one in five patients. A higher WFNS grade and the occurrence of seizures are associated with TS; therefore, screening for TS should be performed in these patients.

Evaluation of Pelvic Circular Compression Devices in Severely Injured Trauma Patients with Pelvic Fractures.

Background: The role of pelvic circumferential compression devices (PCCD) is to temporarily stabilize the pelvic ring, reduce its volume and to tamponade bleeding. The purpose of this study was to evaluate the effect of PCCDs on mortality and bleeding in severely injured trauma patients, using a large registry database.Methods: We performed a retrospective analysis of all patients registered in the Trauma Register DGU® between 2015 and 2016. The study was limited to directly admitted patients who were alive on admission, with an injury severity score (ISS) of 9 or higher, with an Abbreviated Injury Scale AISpelvis of 3-5, aged at least 16, and with complete status documentation on pelvic circular compression devices (PCCD) and mortality. A cohort analysis was undertaken of patients suffering from relevant pelvic fractures. Data were collected on mortality and requirements for blood transfusion. The observed outcome was compared with the expected outcome as derived from version II of the Revised Injury Severity Classification (RISC II) and adjusted accordingly. A Standardized Mortality Ratio (SMR) was also calculated.Results: A total of 9,910 patients were included. 1,103 of 9,910 patients suffered from a relevant pelvic trauma (AISpelvis = 3-5). Only 41% (454 cases) of these received a PCCD. PCCD application had no significant effect on mortality and did not decrease the need for blood transfusion in the multivariate regression analysis. However, in this cohort, the application of a PCCD is a general indicator for a critical patient with increased mortality (12.0% no PCCD applied vs. 23.2% PCCD applied prehospital vs. 27.1% PCCD applied in the emergency department). The ISS was higher in patients with PCCD (34.12 ± 16.4 vs. 27.9 ± 13.8; p < 0.001).Conclusion: PCCD was applied more often in patients with severe pelvic trauma according to ISS and AISpelvis as well with deterioration in circulatory status. PCCDs did not reduce mortality or reduce the need for blood transfusion.Trial registration: TR-DGU ID 2017-003, March 2017; German clinical trial register DRKS00024948.

Hyperoxia is Dose-Dependently Associated with an Increase of Unfavorable Outcomes in Ventilated Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Cohort Study.

BACKGROUND: Adequate oxygenation in patients with aneurysmal subarachnoid hemorrhage (SAH) is imperative. However, hyperoxia increases formation of reactive oxygen species and may be associated with a dose-dependent toxicity. We postulated a threshold for arterial partial pressure of oxygen (paO2) above which toxicity effects precipitate and sought to study the effects on 30-day mortality, favorable outcome at discharge and at 3 months, and delayed cerebral ischemia. METHODS: In this retrospective single-center cohort study, patients with SAH and mechanical ventilation > 72 h were included. Oxygen integrals were calculated above the following thresholds: 80, 100, 120, and 150 mm Hg and time-weighted mean paO2. All calculations were done from admission to end of day 1, day 3, and day 14. We conducted multivariable logistic regression analyses adjusted for age, sex, duration of ventilation, and Hunt and Hess grade. Time-weighted mean paO2 was categorized by quartiles. Favorable outcome was defined as Glasgow Outcome Scale scores of 4 and 5. RESULTS: From November 2010 to February 2021, 282 of 549 patients fulfilled the inclusion criteria. Odds ratios for 30-day mortality increased dose dependently and were as follows: 1.07 (95% confidence interval [CI] 1.03-1.11; p = 0.001) for each 1 mm Hg per day above 80 mm Hg; 1.16 (95% CI 1.07-1.27), above 100 mm Hg; 1.36 (95% CI 1.15-1.61), above 120 mm Hg; and 1.59 (95% CI 1.22-2.08), above 150 mm Hg (all p < 0.001) at day 14. For favorable outcome at 3 months, odds ratios were 0.96 (95% CI 0.92-0.99) for each 1 mm Hg per day above 80 mm Hg; 0.90 (95% CI 0.84-0.98), above 100 mm Hg; 0.83 (95% CI 0.72-0.97), above 120 mm Hg; and 0.77 (95% CI 0.61-0.97), above 150 mm Hg (all p < 0.05). For time-weighted mean paO2, lowest 30-day mortality and highest favorable outcome at 3 months were found in the second quartile (78-85 mm Hg). Thirty-day mortality increased above 93 mm Hg (fourth quartile), with an odds ratio of 3.4 (95% CI 1.4-8.4, p = 0.007). Odds ratios for favorable outcome at 3 months were 0.28 (95% CI 0.12-0.69), 0.27 (95% CI 0.11-0.67), and 0.24 (95% CI 0.10-0.59) for the first, third, and fourth quartiles, respectively (all p < 0.01). No significant association was found at day 1 and day 3, for favorable outcome at discharge, or for delayed cerebral ischemia. CONCLUSIONS: Integrals above the defined paO2 thresholds were dose-dependently associated with an increase in mortality in ventilated patients with SAH. When we considered time-weighted mean paO2, unfavorable outcomes and 30-day mortality were more frequent both below and above a certain range. Unfavorable outcomes increased in paO2 ranges usually defined as normoxia. This emphasizes the necessity to further characterize oxygenation thresholds in ventilated patients with SAH in prospective clinical studies.

The faster the better? Time to first CT scan after admission in moderate-to-severe traumatic brain injury and its association with mortality.

Fast acquisition of a first computed tomography (CT) scan after traumatic brain injury (TBI) is recommended. This study is aimed at investigating whether the length of the period preceding initial CT scan influences mortality in patients with leading TBI. A retrospective cohort analysis of patients registered in the TraumaRegister DGU® was conducted including adult patients with TBI, defined as Abbreviated Injury ScaleHead ≥ 3 and GCS ≤ 13 who had been treated in level 1 or 2 trauma centers from 2007-2016. Patients were grouped according to time intervals either from trauma or from admission to CT. A total of 6904 patients met the inclusion criteria. Mean time period from trauma to hospital admission was 68.8 min. From admission to first CT, a mean of 19.0 min elapsed. Trauma severity was higher in groups with a longer duration from trauma to CT as represented by a mean (± standard deviation) Injury Severity Score (ISS) of 19.8 ± 9.0, 20.7 ± 9.3, and 21.4 ± 7.5 and similar distribution of mortality of 24.9%, 29.9%, and 36.3% in the ≤ 60-min, 61-120-min, and ≥ 121-min groups, respectively. An adjusted multivariable logistic regression model showed a significant influence of the level of the trauma center (p = 0.037) but not for interval from admission to CT (p = 0.528). TBI patients with a longer time span from trauma to first CT were more severely injured and demonstrated a worse prognosis, but received a CT scan faster when duration from admission is observed. The duration until the CT scan was obtained showed no significant impact on the mortality.

Operative versus non-operative treatment of traumatic brain injuries in patients 80 years of age or older.

Traumatic brain injury (TBI) in older adults is an increasing issue in modern medicine. Nevertheless, it remains unclear which patients presenting with TBI and 80 years of age or older benefit from an operative treatment. The aim of this study was to explore the effect of an operative treatment in isolated TBI patients ≥ 80 years of age. Data were derived from the TraumaRegister DGU® from 2002 to 2016. Inclusion criteria were ≥ 80 years of age, an Abbreviated Injury ScaleHead (AIS) ≥ 3, and an AISNon-Head ≤ 1. The cohort was split in operatively and non-operatively treated patients, and outcome was assessed at discharge using the Glasgow Outcome Scale (GOS). A favorable outcome was defined as a GOS of 4 or 5. A total of 1.693 patients (431 operatively and 1.262 non-operatively treated patients) were analyzed. Mortality rate was 54.4% (687 patients) in the non-operative group and 49.4% in the operative group. Simultaneously, there were more patients discharged with a GOS 2 (persistent vegetative state) in the operative group (7.9%, 34 patients) than in the non-operative group (1.0%, 13 patients). An analysis of the operatively treated patients showed an association between a higher mortality risk and brainstem hemorrhage (p = 0.04), fixed pupils (p = 0.001), initial intubation (p = 0.03), and an AISHead of 5/6 (p = 0.03). Patients 80 years of age or older seem to benefit from an operative treatment regarding mortality rate. However, there has been a higher rate of a poor neurological outcome particularly with regard to persistent vegetative state in the operative treatment group at discharge.

The burden of headache following aneurysmal subarachnoid hemorrhage: a prospective single-center cross-sectional analysis.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) as a serious type of stroke is frequently accompanied by a so-called initial thunderclap headache. However, the occurrence of burdensome long-term headache following SAH has never been studied in detail so far. The aim of this study was to determine the prevalence and characteristics of long-term burdensome headache in good-grade SAH patients as well as its relation to health-related quality of life (HR-QOL). METHODS: All SAH cases treated between January 2014 and December 2016 with preserved consciousness at hospital discharge were prospectively interviewed regarding burdensome headache in 2018. Study participants were subsequently scrutinized by means of a standardized postal survey comprising validated pain and HR-QOL questionnaires. A retrospective chart review provided data on the initial treatment. RESULTS: A total of 93 out of 145 eligible SAH patients participated in the study (62 females). A total of 41% (38/93) of subjects indicated burdensome headache at follow-up (mean 32.6 ± 9.3 months). Comparison between patients with (HA+) and without long-term headache (HA-) revealed significantly younger mean age (47.9 ± 11.8 vs. 55.6 ± 10.3 years; p < .01) as well as more favorable neurological conditions (WFNS I/II: 95% vs. 75%; p = .03) in HA+ cases. The mean average headache of the HA+ group was 3.7 ± 2.3 (10-point numeric rating scale), and the mean maximum headache intensity was 5.7 ± 2.9. Pain and HR-QOL scores demonstrated profound alterations in HA+ compared to HA- patients. CONCLUSIONS: Our results suggest that a considerable proportion of SAH patients suffers from burdensome headache even years after the hemorrhage. Moreover, long-term headache is associated with reduced HR-QOL in these cases.

Decompressive craniectomy in malignant MCA infarction in times of mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomies (MT) in stroke have changed the standard treatment regimen with a continuous increase of MTs during the last years. A subsequent reduction in the rates of decompressive craniectomies (DC) as well as a change in clinical characteristics of patients undergoing an additional DC after MT may be assumed. Therefore, objective of this study was to investigate the influence of nowadays regularly performed MT on patients undergoing DC. METHODS: Patients with DC due to cerebral infarctions between January 2009 and January 2018 were included. Patients' clinical presentation and surgical parameters were collected retrospectively. Initial GCS and NIHSS, extent of the stroke, time interval from symptom onset to DC, and neurological outcome were compared between patients with and without thrombectomy. RESULTS: A total of 5469 ischemic strokes were treated in the investigated period, leading to DC in 119 cases (2.2%). A decrease in the rate of performed DCs was recorded: in 2009, 2.8% of ischemic stroke patients underwent surgery compared to 1.9% in 2017. In the meantime, the number of MTs in our center has increased from 84 in 2014 to 160 in 2017. MT was performed in 32 patients prior to DC. No significant differences could be seen between the groups regarding age, initial NIHSS (median 18 in both groups, p = 0.81), extent of the infarctions prior to DC (median ASPECTS 0 in both groups, p = 0.87), time interval from symptom onset to DC, and neurological outcome. CONCLUSIONS: The introduction of routinely performed MT as part of the standard treatment regimen for ischemic stroke has led to a decrease in DCs. However, DC patients with and without MT showed no differences regarding their initial clinical criteria and outcome. These results suggest that earlier DC studies in patients with MCA infarction also apply for the collective of thrombectomized patients.

Rate and risk factors for a hyperactivity delirium in patients with aneurysmal subarachnoid haemorrhage.

Hyperactive delirium (agitation) is a common complication in patients on intensive care units and can be assessed by the Richmond Agitation and Sedation Scale (RASS) in principle. However, the role of agitation in patients with aneurysmal subarachnoid haemorrhage (SAH) is poorly understood. We performed a retrospective analysis to identify risk factors for the development of a hyperactive delirium and its functional consequences for neurological outcome. Three hundred thirty-eight patients with SAH were screened in this study resulting in 212 patients which reached at least once a RASS of 0 and were eligible for further analysis. Clinical characteristics were analysed towards the occurrence of a hyperactive delirium. Neurological outcome at discharge and follow-up was assessed using the Glasgow Outcome Scale. Seventy-eight of 212 patients (36.8%) developed a hyperactive delirium; the duration ranged from 1 to 11 days. Multivariate regression revealed initial hydrocephalus (odds ratio (OR) 3.21 95% confidence interval (CI) [1.33-7.70]; p = 0.01), microsurgical clipping (OR 3.70 95%CI 1.71-8.01]; p = 0.001), male gender (OR 1.97 95%CI [1.05-3.85]; p = 0.047) and a higher Graeb score (OR 1.11 95%CI [1.00-1.22]; p = 0.043) to be significantly associated with the development of agitation. Medical history of psychiatric disorders, alcohol or nicotine abuse showed no correlation with agitation. Cox regression analysis revealed no significant influence of agitation towards unfavourable outcome at discharge or follow-up. We provide four independent risk factors for the development of agitation in SAH patients. Our study emphasizes the specific entity of agitation in patients with SAH and underscores its relevance in neurological patients.

Early clinical course after aneurysmal subarachnoid hemorrhage: comparison of patients treated with Woven EndoBridge, microsurgical clipping, or endovascular coiling.

BACKGROUND: The Woven EndoBridge (WEB) device has been increasingly used for the treatment of intracranial aneurysms after aneurysmal subarachnoid hemorrhage (SAH). Still, recent major clinical trials on patient management after SAH have defined WEB embolization as an exclusion criterion. In an analysis of an unselected patient cohort, we evaluate the early clinical course of SAH patients after WEB treatment compared to those treated with endovascular coiling or surgical clipping. METHODS: Data of all patients with proven SAH who were either treated with a WEB device, coil embolization, or neurosurgical clipping between March 2015 and August 2018 was systematically reviewed. Clinical parameters on intensive care unit (ICU), medical history and mortality rates were evaluated and compared between the different treatment approaches. RESULTS: Of all 201 patients included, 107 patients received endovascular coil embolization, 56 patients were treated with clipping and in 38 cases a WEB device was placed. The overall mortality was 17.9%. Thirteen patients (34.2%) in the WEB group had a Hunt and Hess grade > 3. Essential medical factors showed no clinically relevant differences between the treatment groups, and the analyzed blood parameters were predominantly within physiological limits without any relevant outliers. The Hunt and Hess grade but not the treatment modality was identified as independent risk-factor associated with ICU-mortality in the overall cohort (p < 0.001). CONCLUSION: In this study, there was no difference in the early clinical course between those treated with WEB embolization, coil embolization, or neurosurgical clipping. Since WEB embolization is a valuable treatment alternative to coiling, it seems not justified to exclude this procedure from upcoming clinical SAH trials, yet the clinical long-term outcome, aneurysm occlusion, and retreatment rates have to be analyzed in further studies. CLINICAL TRIAL REGISTRATION NUMBER: not applicable.

Posterior vertebral column resection with 360-degree osteosynthesis in osteoporotic kyphotic deformity and spinal cord compression.

Osteoporotic fractures with severe kyphosis and neurologic deficits often require decompression and stabilisation. To reduce the risk of procedure-related complications, single-stage posterolateral vertebrectomy and a 360-degree fusion can be performed. An adequate reduction of kyphotic deformity through this approach has not been reported. The aim of this study is to investigate the efficacy of kyphotic deformity reduction by this approach in osteoporotic situation. A retrospective analysis and chart review was performed for 10 consecutive patients who underwent posterolateral decompression and posterior vertebrectomy with dorsal mesh stabilisation and reduction of kyphotic deformity. Preoperative back pain was 8.6 on a visual analogue scale; it was reduced to 5.5 at discharge and 3.7 at the latest follow-up (18 months). The Frankel score improved from D to E (three patients) or was equal (E). Radiological segmental kyphosis was corrected from a mean of 25° to 5° (p < 0.008) postoperatively with a loss of 3° at follow-up (p < 0.005). Single-stage posterolateral vertebrectomy allow for a fast and safe reconstitution/preservation of neurological function in patients with osteoporotic fracture and kyphotic deformity. A significant correction of often-accompanied hyperkyphosis is possible without neurological deterioration and with an improved sagittal profile and good pain reduction.

Rate and impact of multidrug-resistant organisms in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Multidrug-resistant organisms (MDRO) are an increasing problem in critical care medicine. This study describes for the first time the rate and impact of MDRO in patients suffering from aneurysmal subarachnoid hemorrhage (SAH). METHODS: Anonymized data of SAH patients admitted to our institution from November 2010 to August 2017 were retrospectively reviewed. Patients with microbiological tests positive for MDRO were identified. Screening of MDRO was in consensus with national recommendations. RESULTS: 449 SAH patients were reviewed with 18 patients (prevalence: four MDRO-positive patients per 100 SAH patients) having positive tests for MDRO during their hospital stay. The prevalence upon admission was 1.3 MDRO-positive patients per 100 patients. The acquisition rate was 1.1 MDRO-positive patients per 1000 hospital days. Patients positive for an MDRO had a significantly extended length of stay in intensive care (mean ± SD 26.7 ± 13.0 versus 18.4 ± 11.7 days, p = 0.004) and in hospital (mean ± SD 33.9 ± 12.4 versus 24.4 ± 12.6 days, p = 0.002). MDRO detection was associated with a significant prolonged duration of mechanical ventilation (median (IQR) 254.0 (14.9-632.8) versus 37.5 (3.3-277.0) hours, p = 0.02). There was no statistically significant effect on the Glasgow Outcome Scale (GOS) at discharge and at follow-up after 164.4 ± 113.0 days. CONCLUSIONS: MDRO positivity is present in 4% of aneurysmal SAH patients. It seems to be associated with a prolonged length of stay and prolonged duration of mechanical ventilation. The importance of infection control standards in neurointensive care units is emphasized.

Intrathecal penetration of meropenem and vancomycin administered by continuous infusion in patients suffering from ventriculitis-a retrospective analysis.

BACKGROUND: Vancomycin and meropenem are frequently used as empiric treatment for ventriculitis. Penetration into the cerebrospinal fluid (CSF) depends on various factors with a high inter-individual variability. Because attaining and maintaining adequate concentrations of meropenem and vancomycin in the CSF is crucial for their bactericidal effect, we introduced a routine therapeutic drug monitoring (TDM) from CSF and serum for both antibiotics. We studied the antibiotic penetration into the CSF. METHODS: Patient data including serum and CSF concentrations for meropenem and vancomycin were collected in a retrospective fashion. Antibiotic CSF penetration ratio was calculated for each patient. Antibiotics were administered by continuous infusion aiming for serum target concentrations of 20-30 mg/L for vancomycin and 16-32 mg/L for meropenem. RESULTS: Twenty-two patients with 36 CSF/serum pairs for meropenem and 43 pairs for vancomycin were studied. No patient suffered from renal or liver insufficiency. Mean vancomycin serum concentration was 22 ± 8 mg/L and the mean CSF concentration 4.5 ± 2.6 mg/L. CSF penetration was 20 ± 11% (coefficient of determination (R2) 0.02). For meropenem, the mean serum concentration was 30.7 ± 14.9 mg/L, mean CSF concentration 5.5 ± 5.2 mg/L, and a penetration of 18 ± 12%, R2 = 0.42. CONCLUSION: Penetration of meropenem and vancomycin into the CSF is low while showing a high interindividual variability. Various patients in our study cohort were at risk for insufficient target attainment in CSF. Continuous administration of antibiotics under routine TDM appears to be a feasible and reasonable approach for optimization of intrathecal drug levels in patients suffering from ventriculitis. TDM might guide individual dosing adaptation and efforts to predict the CSF penetration of meropenem and vancomycin in cases of ventriculitis.

Asymmetric and Symmetric Dimethylarginines are Markers of Delayed Cerebral Ischemia and Neurological Outcome in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is the major cause of lethality and neuronal damage in patients who survived the primary subarachnoid hemorrhage (SAH). Asymmetric and symmetric dimethylarginines (ADMA and SDMA) inhibit nitric oxide production from L-arginine via distinct mechanisms. Elevated ADMA levels are associated with vasospasm after SAH. We aimed to study the time course of ADMA and SDMA in plasma and ventricular cerebrospinal fluid (CSF) and their associations with DCI and outcome. METHODS: We measured ADMA and SDMA in 34 SAH patients with an external ventricular drain at admission and on days 3, 6, 8, 12, and 15 and followed them up for clinical status and neurological outcome until 30 days post-discharge. DCI was defined as the appearance of new infarctions on cerebral computed tomography or magnetic resonance imaging. RESULTS: ADMA and SDMA plasma concentrations did not differ significantly at baseline between patients who suffered DCI (N = 14; 41%) and not; however, plasma ADMA reached a peak on days 8 and 15 after hemorrhage in patients with DCI (0.81-0.91 µmol/l). Baseline plasma L-arginine/ADMA ratio was significantly lower in patients with DCI (57.1 [34.3; 70.8] vs. 68.7 [55.7; 96.2]; p < 0.05). ADMA and SDMA concentrations in CSF were significantly higher in patients with DCI than without. In multivariable-adjusted linear regression models, CSF ADMA was negatively associated with the incidence of DCI (OR 0.03 [0.02-0.70]; p = 0.04), whereas CSF SDMA on the day of hemorrhage predicted poor neurological outcome until 30 days after discharge (OR 22.4 [1.21-416.02]; p = 0.04). CONCLUSIONS: Our study shows that ADMA and the L-arginine/ADMA ratio are associated with the incidence of DCI after SAH. By contrast, SDMA was associated with initial neuronal damage and poor neurological outcome after SAH. These data support the hypothesis that ADMA and L-arginine affect the pathophysiology of cerebral ischemia after SAH, while SDMA is a biomarker of neurological outcome after SAH.

Reducing kyphotic deformity by posterior vertebral column resection with 360° osteosynthesis in metastatic epidural spinal cord compression (MESCC).

PURPOSE: Metastatic epidural spinal cord compression (MESCC) often requires anterior-posterior decompression and stabilization. To reduce approach-related complications, single-stage posterolateral vertebrectomy and 360° fusion is often performed. However, a sufficient reduction of kyphotic deformity through this approach has not been reported. The purpose of this study is to investigate the efficacy of kyphotic deformity reduction by this approach in MESCC. METHODS: A retrospective analysis and chart review was performed for 14 consecutive patients who underwent a vertebrectomy and decompression from a posterolateral approach. Anterior mesh stabilization of the ventral column is used as hypomochlion for the posterior compression manoeuvre, which leads to reduction of the kyphotic deformity. RESULTS: Pre-operative back pain was 7.2 on a visual analogue scale. Back pain was reduced to 4.4 at discharge and 2.0 at the latest follow-up with a mean follow-up of 12 months (p < 0.001). The Frankel score remains constant or improved from D to E. Radiological segmental kyphosis was corrected from a mean of 16° to 4° (p < 0.001) post-operatively with a loss of 3° at the final follow-up, but still with significant corrections compared with the pre-operative measurements (p < 0.003). CONCLUSION: Single-stage posterolateral vertebrectomy and reconstruction is a safe and less invasive approach that allows a sufficient reduction of hyperkyphosis and preservation of neurological function in patients with MESCC. This approach is an efficient alternative to anterior-posterior fusion with good pain reduction and improved sagittal profile.

Somatosensory evoked potentials in patients with high-grade aneurysmal subarachnoid hemorrhage.

OBJECTIVE The aim of this prospective study was to investigate the value of somatosensory evoked potentials (SEPs) in predicting outcome in patients with high-grade aneurysmal subarachnoid hemorrhage (SAH). METHODS Between January 2013 and January 2015, 48 patients with high-grade SAH (Hunt and Hess Grade III, IV, or V) who were admitted within 3 days after hemorrhage were enrolled in the study. Right and left median and tibial nerve SEPs were recorded on Day 3 after hemorrhage and recorded again 2 weeks later. Glasgow Outcome Scale (GOS) scores were determined 6 months after hemorrhage and dichotomized as poor (Scores 1-3) or good (Scores 4-5). Results of SEP measurements were dichotomized (present or missing cortical responses or normal or prolonged latencies) for each nerve and side. These variables were summed and tested using logistic regression and a receiver operating characteristic curve to assess the value of SEPs in predicting long-term outcome. RESULTS At the 6-month follow-up visit, 29 (60.4%) patients had a good outcome, and 19 (39.6%) had a poor outcome. The first SEP measurement did not correlate with clinical outcome (area under the curve [AUC] 0.69, p = 0.52). At the second measurement of median nerve SEPs, all patients with a good outcome had cortical responses present bilaterally, and none of them had bilateral prolonged latencies (p = 0.014 and 0.003, respectively). In tibial nerve SEPs, 7.7% of the patients with a good GOS score had one or more missing cortical responses, and bilateral prolonged latencies were found in 23% (p = 0.001 and 0.034, respectively). The second measurement correlated with the outcome regarding each of the median and tibial nerve SEPs and the combination of both (AUC 0.75 [p = 0.010], 0.793 [p = 0.003], and 0.81 [p = 0.001], respectively). CONCLUSIONS Early SEP measurement after SAH did not correlate with clinical outcome, but measurement of median and tibial nerve SEPs 2 weeks after a hemorrhage did predict long-term outcome in patients with high-grade SAH.

Does usage of a parachute in contrast to free fall prevent major trauma?: a prospective randomised-controlled trial in rag dolls.

PURPOSE: It is undisputed for more than 200 years that the use of a parachute prevents major trauma when falling from a great height. Nevertheless up to date no prospective randomised controlled trial has proven the superiority in preventing trauma when falling from a great height instead of a free fall. The aim of this prospective randomised controlled trial was to prove the effectiveness of a parachute when falling from great height. METHODS: In this prospective randomised-controlled trial a commercially acquirable rag doll was prepared for the purposes of the study design as in accordance to the Declaration of Helsinki, the participation of human beings in this trial was impossible. Twenty-five falls were performed with a parachute compatible to the height and weight of the doll. In the control group, another 25 falls were realised without a parachute. The main outcome measures were the rate of head injury; cervical, thoracic, lumbar, and pelvic fractures; and pneumothoraxes, hepatic, spleen, and bladder injuries in the control and parachute groups. An interdisciplinary team consisting of a specialised trauma surgeon, two neurosurgeons, and a coroner examined the rag doll for injuries. Additionally, whole-body computed tomography scans were performed to identify the injuries. RESULTS: All 50 falls-25 with the use of a parachute, 25 without a parachute-were successfully performed. Head injuries (right hemisphere p = 0.008, left hemisphere p = 0.004), cervical trauma (p < 0.001), thoracic trauma (p < 0.001), lumbar trauma (p < 0.001), pelvic trauma (p < 0.001), and hepatic, spleen, and bladder injures (p < 0.001) occurred more often in the control group. Only the pneumothoraxes showed no statistically significant difference between the control and parachute groups. CONCLUSIONS: A parachute is an effective tool to prevent major trauma when falling from a great height.