Long-term outcome in new onset refractory status epilepticus: a retrospective study.

BACKGROUND: New onset refractory status epilepticus (NORSE) is a neurologic emergency without an immediately identifiable cause. The complicated and long ICU stay of the patients can lead to perceiving a prolongation of therapies as futile. However, a recovery is possible even in severe cases. This retrospective study investigates ICU treatments, short- and long-term outcome and ethical decisions of a case series of patients with NORSE. METHODS: Overall, 283 adults were admitted with status epilepticus (SE) to the Neurocritical Care Unit of the University Hospital Zurich, Switzerland, between 01.2010 and 12.2022. Of them, 25 had a NORSE. We collected demographic, clinical, therapeutic and outcome data. Descriptive statistics was performed. RESULTS: Most patients were female (68%), previously healthy (Charlson comorbidity index 1 [0-4]) and relatively young (54 ± 17 years). 96% presented with super-refractory SE. Despite extensive workup, the majority (68%) of cases remained cryptogenic. Most patients had a long and complicated ICU stay. The in-hospital mortality was 36% (n = 9). The mortality at last available follow-up was 56% (n = 14) on average 30 months after ICU admission. The cause of in-hospital death for 89% (n = 8) of the patients was the withholding/withdrawing of therapies. Medical staff except for one patient triggered the decision. The end of life (EOL) decision was taken 29 [12-51] days after the ICU admission. Death occurred on day 6 [1-8.5] after the decision was taken. The functional outcome improved over time for 13/16 (81%) hospital survivors (median mRS at hospital discharge 4 [3.75-5] vs. median mRS at last available follow-up 2 [1.75-3], p < 0.001). CONCLUSIONS: Our data suggest that the long-term outcome can still be favorable in NORSE survivors, despite a prolonged and complicated ICU stay. Clinicians should be careful in taking EOL decisions to avoid the risk of a self-fulfilling prophecy. Our results encourage clinicians to continue treatment even in initially refractory cases.

Sex differences in the use of mechanical ventilation in a neurointensive care population: a retrospective study.

BACKGROUND: In the general intensive care unit (ICU) women receive invasive mechanical ventilation (IMV) less frequently than men. We investigated whether sex differences in the use of IMV also exist in the neurocritical care unit (NCCU), where patients are intubated not only due to respiratory failure but also due to neurological impairment. METHODS: This retrospective single-centre study included adults admitted to the NCCU of the University Hospital Zurich between January 2018 and August 2021 with neurological or neurosurgical main diagnosis. We collected data on demographics, intubation, re-intubation, tracheotomy, and duration of IMV or other forms of respiratory support from the Swiss ICU registry or the medical records. A descriptive statistics was performed. Baseline and outcome characteristics were compared by sex in the whole population and in subgroup analysis. RESULTS: Overall, 963 patients were included. No differences between sexes in the use and duration of IMV, frequency of emergency or planned intubations, tracheostomy were found. The duration of oxygen support was longer in women (men 2 [2, 4] vs. women 3 [1, 6] days, p = 0.018), who were more often admitted due to subarachnoid hemorrhage (SAH). No difference could be found after correction for age, diagnosis of admission and severity of disease. CONCLUSION: In this NCCU population and differently from the general ICU population, we found no difference by sex in the frequency and duration of IMV, intubation, reintubation, tracheotomy and non-invasive ventilation support. These results suggest that the differences in provision of care by sex reported in the general ICU population may be diagnosis-dependent. The difference in duration of oxygen supplementation observed in our population can be explained by the higher prevalence of SAH in women, where we aim for higher oxygenation targets due to the specific risk of vasospasm.

Nonconvulsive status epilepticus in neurocritical care: A critical reappraisal of outcome prediction scores.

OBJECTIVE: Nonconvulsive status epilepticus (NCSE) is a frequent condition in the neurocritical care unit (NCCU) patient population, with high morbidity and mortality. We aimed to assess the validity of available outcome prediction scores for prognostication in an NCCU patient population in relation to their admission reason (NCSE vs. non-NCSE related). METHODS: All 196 consecutive patients diagnosed with NCSE during the NCCU stay between January 2010 and December 2020 were included. Demographics, Simplified Acute Physiology Score II (SAPS II), NCSE characteristics, and in-hospital and 3-month outcome were extracted from the electronic charts. Status Epilepticus Severity Score (STESS), Epidemiology-Based Mortality Score in Status Epilepticus (EMSE), and encephalitis, NCSE, diazepam resistance, imaging features, and tracheal intubation score (END-IT) were evaluated as previously described. Univariable and multivariable analysis and comparison of sensitivity/specificity/positive and negative predictive values/accuracy were performed. RESULTS: A total of 30.1% died during the hospital stay, and 63.5% of survivors did not achieve favorable outcome at 3 months after onset of NCSE. Patients admitted primarily due to NCSE had longer NCSE duration and were more likely to be intubated at diagnosis. The receiver operating characteristic (ROC) for SAPS II, EMSE, and STESS when predicting mortality was between .683 and .762. The ROC for SAPS II, EMSE, STESS, and END-IT when predicting 3-month outcome was between .649 and .710. The accuracy in predicting mortality/outcome was low, when considering both proposed cutoffs and optimized cutoffs (estimated using the Youden Index) as well as when adjusting for admission reason. SIGNIFICANCE: The scores EMSE, STESS, and END-IT perform poorly when predicting outcome of patients with NCSE in an NCCU environment. They should be interpreted cautiously and only in conjunction with other clinical data in this particular patient group.

The role of neuronal antibodies in cryptogenic new onset refractory status epilepticus.

Most cases with new onset refractory status epilepticus (NORSE) remain cryptogenic despite extensive diagnostic workup. The aim of this study was to analyze the etiology and clinical features of NORSE and investigate known or potentially novel autoantibodies in cryptogenic NORSE (cNORSE). We retrospectively assessed the medical records of adults with status epilepticus at a Swiss tertiary referral center between 2010 and 2021. Demographic, diagnostic, therapeutic, and outcome parameters were characterized. We performed post hoc screening for known or potentially novel autoantibodies including immunohistochemistry (IHC) on rat brain with cerebrospinal fluid (CSF) and serum samples of cNORSE. Twenty patients with NORSE were identified. Etiologies included infections (n = 4), Creutzfeldt-Jakob disease (n = 1), CASPR2 autoimmune encephalitis (n = 1), and carotid artery stenosis with recurrent perfusion deficit (n = 1). Thirteen cases (65%) were cryptogenic despite detailed evaluation. A posteriori IHC for neuronal autoantibodies yielded negative results in all available serum (n = 11) and CSF (n = 9) samples of cNORSE. Our results suggest that neuronal antibodies are unlikely to play a major role in the pathogenesis of cNORSE. Future studies should rather focus on other-especially T-cell- and cytokine-mediated-mechanisms of autoinflammation in this devastating disease, which is far too poorly understood so far.

Spontaneous empyema and brain abscess in an intensive care population: clinical presentation, microbiology, and factors associated with outcome.

BACKGROUND: Data on critically ill patients with spontaneous empyema or brain abscess are limited. The aim was to evaluate clinical presentations, factors, and microbiological findings associated with the outcome in patients treated in a Neurocritical Care Unit. METHODS: In this retrospective study, we analyzed 45 out of 101 screened patients with spontaneous epidural or subdural empyema and/or brain abscess treated at a tertiary care center between January 2012 and December 2019. Patients with postoperative infections or spinal abscess were excluded. Medical records were reviewed for baseline characteristics, origin of infection, laboratory and microbiology findings, and treatment characteristics. The outcome was determined using the Glasgow outcome scale extended (GOSE). RESULTS: Favorable outcome (GOSE 5-8) was achieved in 38 of 45 patients (84%). Four patients died (9%), three remained severely disabled (7%). Unfavorable outcome was associated with a decreased level of consciousness at admission (Glasgow coma scale < 9) (43% versus 3%; p = 0.009), need of vasopressors (71% versus 11%; p = 0.002), sepsis (43% versus 8%; p = 0.013), higher age (65.1 ± 15.7 versus 46.9 ± 17.5 years; p = 0.014), shorter time between symptoms onset and ICU admission (5 ± 2.4 days versus 11.6 ± 16.8 days; p = 0.013), and higher median C-reactive protein (CRP) serum levels (206 mg/l, range 15-259 mg/l versus 17.5 mg/l, range 3.3-72.7 mg/l; p = 0.036). With antibiotics adapted according to culture sensitivities in the first 2 weeks, neuroimaging revealed a progression of empyema or abscess in 45% of the cases. CONCLUSION: Favorable outcome can be achieved in a considerable proportion of an intensive care population with spontaneous empyema or brain abscess. Sepsis and more frequent need for vasopressors, associated with unfavorable outcome, indicate a fulminant course of a not only cerebral but systemic infection. Change of antibiotic therapy according to microbiological findings in the first 2 weeks should be exercised with great caution.

Influence of gender and sexual hormones on outcomes after pituitary surgery: a systematic review and meta-analysis.

BACKGROUND: Although there is an increasing body of evidence showing gender differences in various medical domains as well as presentation and biology of pituitary adenoma (PA), gender differences regarding outcome of patients who underwent transsphenoidal resection of PA are poorly understood. The aim of this study was to identify gender differences in PA surgery. METHODS: The PubMed/MEDLINE database was searched up to April 2023 to identify eligible articles. Quality appraisal and extraction were performed in duplicate. RESULTS: A total of 40 studies including 4989 patients were included in this systematic review and meta-analysis. Our analysis showed odds ratio of postoperative biochemical remission in males vs. females of 0.83 (95% CI 0.59-1.15, P = 0.26), odds ratio of gross total resection in male vs. female patients of 0.68 (95% CI 0.34-1.39, P = 0.30), odds ratio of postoperative diabetes insipidus in male vs. female patients of 0.40 (95% CI 0.26-0.64, P < 0.0001), and a mean difference of preoperative level of prolactin in male vs. female patients of 11.62 (95% CI - 119.04-142.27, P = 0.86). CONCLUSIONS: There was a significantly higher rate of postoperative DI in female patients after endoscopic or microscopic transsphenoidal PA surgery, and although there was some data in isolated studies suggesting influence of gender on postoperative biochemical remission, rate of GTR, and preoperative prolactin levels, these findings could not be confirmed in this meta-analysis and demonstrated no statistically significant effect. Further research is needed and future studies concerning PA surgery should report their data by gender or sexual hormones and ideally further assess their impact on PA surgery.

Broad Range Eubacterial Polymerase Chain Reaction of Cerebrospinal Fluid Reduces the Time to Exclusion of and Costs Associated with Ventriculostomy-Related Infection in Hemorrhagic Stroke.

BACKGROUND: Patients with hemorrhagic stroke and an external ventricular drain in situ are at risk for ventriculostomy-related-infections (VRI). Because of the contamination of the cerebrospinal fluid (CSF) with blood and the high frequency of false negative CSF culture, the diagnosis of VRI remains challenging. This study investigated the introduction of CSF broad range eubacterial polymerase chain reaction (ePCR) and its effect on frequency and duration of antibiotic therapy for VRI, neurocritical care unit (NCCU) length of stay, related costs, and outcome. METHODS: Between 2020 and 2022, we prospectively included 193 patients admitted to the NCCU of the University Hospital of Zürich with hemorrhagic stroke and an external ventricular drain for more than 48 h. Patient characteristics, serum inflammatory markers, white blood cell count in CSF, use and duration of antibiotic treatment for VRI, microbiological findings (CSF cultures and ePCR tests), and NCCU length of stay were compared in patients with no infection, noncerebral infection, suspected VRI, and confirmed VRI. Data of patients with suspected VRI of this cohort were compared with a retrospective cohort of patients with suspected VRI treated at our NCCU before the introduction of CSF ePCR testing (2013-2019). RESULTS: Out of 193 patients, 12 (6%) were diagnosed with a confirmed VRI, 66 (34%) with suspected VRI, 90 (47%) with a noncerebral infection, and 25 (13%) had no infection at all. Compared with the retrospective cohort of patients, the use of CSF ePCR resulted in a reduction of patients treated for suspected VRI for the whole duration of 14 days (from 51 to 11%). Furthermore, compared with the retrospective group of patients with suspected VRI (n = 67), after the introduction of CSF ePCR, patients with suspected VRI had shorter antibiotic treatment duration of almost 10 days and, hence, lower related costs with comparable outcome at 3 months. CONCLUSIONS: The use of CSF ePCR to identify VRI resulted in shorter antibiotic treatment duration without changing the outcome, as compared with a retrospective cohort of patients with suspected VRI.

Sex-Related Differences in Patients' Characteristics, Provided Care, and Outcomes Following Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Sex-related differences in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH) are poorly investigated so far. This study elucidates whether sex-related differences in ICH care in a neurocritical care setting exist, particularly regarding provided care, while also taking patient characteristics, and outcomes into account. METHODS: This retrospective single center study includes all consecutive patients with spontaneous ICH admitted to the neurocritical care unit in a 10-year period. Patients' demographics, comorbidities, symptoms at presentation, radiological findings, surgical and medical provided care, intensive care unit mortality and 12 month-mortality, and functional outcome at discharge were compared among men and women. RESULTS: Overall, 398 patients were included (male = 198 and female = 200). No differences in demographics, Charlson Comorbidity Index (CCI), symptoms at presentation, radiological findings, intensive care unit mortality and 12-month mortality were observed among men and women. Men received an external ventricular drain (EVD) for hydrocephalus-therapy significantly more often than women, despite similar location of the ICH and radiographic parameters. In the multivariate analysis, EVD insertion was independently associated with male sex (odds ratio 2.82, 95% confidence interval 1.61-4.95, P < 0.001) irrespective of demographic or radiological features. Functional outcome after ICH as assessed by the modified Rankin scale, was more favorable for women (P = 0.044). CONCLUSIONS: Sex-related differences in patients with ICH regarding to provided neurosurgical care exist. We provide evidence that insertion of EVD is associated with male sex, disregarding clear reasoning. A sex-bias as well as social factors may play a significant role in decision-making for the insertion of an EVD.

Impact of Seizures and Status Epilepticus on Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: We aimed to evaluate the association between seizures as divided by timing and type (seizures or status epilepticus) and outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: All consecutive patients with aSAH admitted to the neurocritical care unit of the University Hospital Zurich between 2016 and 2020 were included. Seizure type and frequency were extracted from electronic patient files. RESULTS: Out of 245 patients, 76 experienced acute symptomatic seizures, with 39 experiencing seizures at onset, 18 experiencing acute seizures, and 19 experiencing acute nonconvulsive status epilepticus (NCSE). Multivariate analysis revealed that acute symptomatic NCSE was an independent predictor of unfavorable outcome (odds ratio 14.20, 95% confidence interval 1.74-116.17, p = 0.013) after correction for age, Hunt-Hess grade, Fisher grade, and delayed cerebral ischemia. Subgroup analysis showed a significant association of all seizures/NCSE with higher Fisher grade (p < 0.001 for acute symptomatic seizures/NCSE, p = 0.031 for remote symptomatic seizures). However, although acute seizures/NCSE (p = 0.750 and 0.060 for acute seizures/NCSE respectively) were not associated with unfavorable outcome in patients with a high Hunt-Hess grade, they were significantly associated with unfavorable outcome in patients with a low Hunt-Hess grade (p = 0.019 and p < 0.001 for acute seizures/NCSE, respectively). CONCLUSIONS: Acute symptomatic NCSE independently predicts unfavorable outcome after aSAH. Seizures and NCSE are associated with unfavorable outcome, particularly in patients with a low Hunt-Hess grade. We propose that NCSE and the ictal or postictal reduction of Glasgow Coma Scale may hamper close clinical evaluation for signs of delayed cerebral ischemia, and thus possibly leading to delayed diagnosis and therapy thereof in patients with a low Hunt-Hess grade.

Transcranial color-coded duplex sonography assessment of cerebrovascular reactivity to carbon dioxide: an interventional study.

BACKGROUND: The investigation of CO2 reactivity (CO2-CVR) is used in the setting of, e.g., traumatic brain injury (TBI). Transcranial color-coded duplex sonography (TCCD) is a promising bedside tool for monitoring cerebral hemodynamics. This study used TCCD to investigate CO2-CVR in volunteers, in sedated and mechanically ventilated patients without TBI and in sedated and mechanically ventilated patients in the acute phase after TBI. METHODS: This interventional investigation was performed between March 2013 and February 2016 at the surgical ICU of the University Hospital of Zurich. Ten volunteers (group 1), ten sedated and mechanically ventilated patients (group 2), and ten patients in the acute phase (12-36 h) after severe TBI (group 3) were included. CO2-CVR to moderate hyperventilation (∆ CO2 -5.5 mmHg) was assessed by TCCD. RESULTS: CO2-CVR was 2.14 (1.20-2.70) %/mmHg in group 1, 2.03 (0.15-3.98) %/mmHg in group 2, and 3.32 (1.18-4.48)%/mmHg in group 3, without significant differences among groups. CONCLUSION: Our data did not yield evidence for altered CO2-CVR in the early phase after TBI examined by TCCD. TRIAL REGISTRATION: Part of this trial was performed as preparation for the interventional trial in TBI patients (clinicaltrials.gov NCT03822026 , 30.01.2019, retrospectively registered).

Diabetes insipidus and syndrome of inappropriate antidiuresis (SIADH) after pituitary surgery: incidence and risk factors.

Electrolyte disorders are relatively frequent and potentially serious complications after pituitary surgery. Both DI (diabetes insipidus) and SIADH (syndrome of inappropriate antidiuresis) can complicate and prolong hospital and intensive care unit stay, and the latter may even be preventable. We aim to assess the incidence of both electrolyte disorders and their risk factors. From a prospective registry of patients who underwent endoscopic transnasal transsphenoidal surgery (TSS) for pituitary adenoma, patients with postoperative DI and SIADH were identified. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of either DI or SIADH. A total of 174 patients were included, of which 73 (42%) were female. Mean age was 54 years (range 20-88). During postoperative hospital stay, 13 (7.5%) patients presenting with DI and 11 (6.3%) with SIADH were identified. Patients who developed DI after surgery had significantly longer hospital stays (p = 0.022), as did those who developed SIADH (p = 0.002). Four (2.3%) patients were discharged with a diagnosis of persistent DI, and 2 (1.1%) with the diagnosis of SIADH. At the last follow-up, 5 (2.9%) patients presented with persistent DI, while none of the patients suffered from SIADH. Younger age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-1.01, p = 0.166) and pituitary apoplexy (OR 2.69, 95% CI 0.53-10.65, p = 0.184) were weakly associated with the occurrence of DI. We identified younger age (OR 0.96, 95% CI 0.92-0.99, p = 0.045) and lower preoperative serum sodium (OR 0.83, 95% CI 0.71-0.95, p = 0.008) as independent risk factors for SIADH. Although we found a weak association among age, pituitary apoplexy, and the occurrence of DI, no independent predictor was identified for DI. For postoperative SIADH however, lower age and preoperative serum sodium were identified as significant predictors. None of these findings were sufficiently supported by preexisting literature. Both electrolyte disorders are exquisitely hard to predict preoperatively, and further research into their early detection and prevention is warranted.

The effect of nimodipine on pulmonary function in artificially ventilated patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Nimodipine is routinely administered in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the effect of nimodipine on oxygen exchange in the lungs is insufficiently explored. METHODS: The study explored nimodipine medication in artificially ventilated patients with aSAH. The data collection period was divided into nimodipine-dependent (ND) and nimodipine-independent (NID) periods. Values for arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) were collected and compared between the periods. Patients were divided in those with lung injury (LI), defined as median Horowitz index (PaO2/FiO2) ≤40 kPa (≤300 mmHg), and without and in those with lower respiratory tract infection (LRTI) and without. RESULTS: A total of 53 out of 150 patients were artificially ventilated, and in 29 patients, the Horowitz index could be compared between ND and NID periods. A linear mixed model showed that during ND period the Horowitz index was 2.3 kPa (95% CI, 1.0-3.5 kPa, P<0.001) lower when compared to NID period. The model suggested that in the presence of LI, ND period is associated with a decrease of the index by 2.8 kPa (95% CI, 1.2-4.3 kPa, P<0.001). The decrease was more pronounced with LRTI than without: 3.4 kPa (95% CI, 0.8-6.1 kPa) vs. 2.1 kPa (95% CI, 0.7-3.4 kPa), P=0.011 and P=0.002, respectively. CONCLUSIONS: In patients with LI or LRTI in the context of aSAH, pulmonary function may worsen with nimodipine treatment. The drop of 2 to 3 kPa of the Horowitz index in patients with no lung pathology may not outweigh the benefits of nimodipine. However, in individuals with concomitant lung injury, the effect may be clinically relevant.

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series.

BACKGROUND AND PURPOSE: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. METHODS: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. RESULTS: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. CONCLUSIONS: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Feasibility of machine learning based predictive modelling of postoperative hyponatremia after pituitary surgery.

PURPOSE: Hyponatremia after pituitary surgery is a frequent finding with potential severe complications and the most common cause for readmission. Several studies have found parameters associated with postoperative hyponatremia, but no reliable specific predictor was described yet. This pilot study evaluates the feasibility of machine learning (ML) algorithms to predict postoperative hyponatremia after resection of pituitary lesions. METHODS: Retrospective screening of a prospective registry of patients who underwent transsphenoidal surgery for pituitary lesions. Hyponatremia within 30 days after surgery was the primary outcome. Several pre- and intraoperative clinical, procedural and laboratory features were selected to train different ML algorithms. Trained models were compared using common performance metrics. Final model was internally validated on the testing dataset. RESULTS: From 207 patients included in the study, 44 (22%) showed a hyponatremia within 30 days postoperatively. Hyponatremic measurements peaked directly postoperatively (day 0-1) and around day 7. Bootstrapped performance metrics of different trained ML-models showed largest area under the receiver operating characteristic curve (AUROC) for the boosted generalized linear model (67.1%), followed by the Naïve Bayes classifier (64.6%). The discriminative capability of the final model was assessed by predicting on unseen dataset. Large AUROC (84.3%; 67.0-96.4), sensitivity (81.8%) and specificity (77.5%) with an overall accuracy of 78.4% (66.7-88.2) was reached. CONCLUSION: Our trained ML-model was able to learn the complex risk factor interactions and showed a high discriminative capability on unseen patient data. In conclusion, ML-methods can predict postoperative hyponatremia and thus potentially reduce morbidity and improve patient safety.

Outcome, Return to Work and Health-Related Costs After Aneurysmal Subarachnoid Hemorrhage.

OBJECT: Data on health-related costs after aneurysmal subarachnoid hemorrhage (aSAH) are limited. The aim was to evaluate outcome, return to work and costs after aSAH with focus on differences between high- and low-grade aSAH (defined as World Federation of Neurological Surgeons [WFNS] grades 4-5 and WFNS 1-3, respectively). METHODS: A cross-sectional study was performed, including all consecutive survivors of aSAH over a 4-year period. A telephone interview was conducted to assess the Glasgow Outcome Scale Extended and employment status before and after aSAH. Direct costs were calculated by multiplying the length of hospitalization by the average daily costs. Indirect costs were calculated for productivity losses until retirement age according to the human capital approach. RESULTS: Follow-up was performed 2.7 years after aSAH (range 1.3-4.6). Favorable outcome was achieved in 114 of 150 patients (76%) and work recovery in 61 of 98 patients (62%) employed prior to aSAH. High-grade compared to low-grade aSAH resulted less frequently in favorable outcome (52% vs. 85%; p < 0.001) and work recovery (39% vs. 69%; p = 0.013). The total costs were € 344.277 (95% CI 268.383-420.171) per patient, mainly accounted to indirect costs (84%). The total costs increased with increasing degree of disability and were greater for high-grade compared to low-grade aSAH (€ 422.496 vs. € 329.193; p = 0.039). The effective costs per patient with favorable outcome were 2.1-fold greater for high-grade compared to low-grade aSAH (€ 308.625 vs. € 134.700). CONCLUSION: Favorable outcome can be achieved in a considerable proportion of high-grade aSAH patients, but costs are greater compared to low-grade aSAH. Further cost-effectiveness studies in the current era of aSAH management are needed.

Cerebral metabolism is not affected by moderate hyperventilation in patients with traumatic brain injury.

BACKGROUND: Hyperventilation-induced hypocapnia (HV) reduces elevated intracranial pressure (ICP), a dangerous and potentially fatal complication of traumatic brain injury (TBI). HV decreases the arteriolar diameter of intracranial vessels, raising the risk of cerebral ischemia. The aim of this study was to characterize the effects of moderate short-term HV in patients with severe TBI by using concomitant monitoring of cerebral metabolism, brain tissue oxygen tension (PbrO2), and cerebral hemodynamics with transcranial color-coded duplex sonography (TCCD). METHODS: This prospective trial was conducted between May 2014 and May 2017 in the surgical intensive care unit (ICU) at the University Hospital of Zurich. Patients with nonpenetrating TBI older than 18 years of age with a Glasgow Coma Scale (GCS) score < 9 at presentation and with ICP monitoring, PbrO2, and/or microdialysis (MD) probes during ICU admission within 36 h after injury were included in our study. Data collection and TCCD measurements were performed at baseline (A), at the beginning of moderate HV (C), after 50 min of moderate HV (D), and after return to baseline (E). Moderate HV was defined as arterial partial pressure of carbon dioxide 4-4.7 kPa. Repeated measures analysis of variance was used to compare variables at the different time points, followed by post hoc analysis with Bonferroni adjustment as appropriate. RESULTS: Eleven patients (64% males, mean age 36 ± 14 years) with an initial median GCS score of 7 (IQR 3-8) were enrolled. During HV, ICP and mean flow velocity (CBFV) in the middle cerebral artery decreased significantly. Glucose, lactate, and pyruvate in the brain extracellular fluid did not change significantly, whereas PbrO2 showed a statistically significant reduction but remained within the normal range. CONCLUSION: Moderate short-term hyperventilation has a potent effect on the cerebral blood flow, as shown by TCCD, with a concomitant ICP reduction. Under the specific conditions of this study, this degree of hyperventilation did not induce pathological alterations of brain metabolites and oxygenation. TRIAL REGISTRATION: NCT03822026 . Registered on 30 January 2019.

Pulmonary hypertension is not a risk factor for grade 3 primary graft dysfunction after lung transplantation.

Grade 3 primary graft dysfunction (PGD3) represents the most important risk factor for patient mortality during the first year after lung transplantation (LTX). We investigated whether pretransplant pulmonary hypertension (PH) is a risk factor for the development of PGD3. This retrospective, single-center cohort study included 96 candidates undergoing right heart catheterization (RHC) prior to being listed for LTX between March 2000 and October 2015. Based on their mean pulmonary artery pressure (mPAP) levels, the patients were classified into 3 groups: (1) <25 mm Hg, (2) 25-34 mm Hg and (3) ≥35 mm Hg. Forty-seven patients were classified in group 1, 31 in group 2, and 18 in group 3. Fifteen recipients (16%, 95%-CI 8-23) developed PGD3. In the univariate analysis, the diagnosis of interstitial lung disease (ILD) compared to COPD (OR: 7.06, P = .005), blood transfusion >1000 mL during surgery (OR: 5.25, P = .005), the need for intra-operative cardio-pulmonary bypass (CPB) or extra-corporeal membrane oxygenation (ECMO) (OR: 4, P = .027), mPAP (OR 1.06, P = .007) and serum high density lipoprotein-cholesterol (HDL-C) (OR 0.09, P = .005) were associated with PGD3. In the multivariable logistic regression analysis, only HDL-C (OR 0.10, P = .016) was associated with PGD3 based on our single-center cohort data analysis.

Low Level of Vegetative State After Traumatic Brain Injury in a Swiss Academic Hospital.

BACKGROUND: No standards exist regarding decision making for comatose patients, especially concerning life-saving treatments. The aim of this retrospective, single-center study was to analyze outcomes and the decision-making process at the end of life (EOL) in patients with traumatic brain injury (TBI) in a Swiss academic tertiary care hospital. METHODS: Consecutive admissions to the surgical intensive care unit (ICU) with stays of at least 48 hours between January 1, 2012 and June 30, 2015 in patients with moderate to severe TBI and with fatality within 6 months after trauma were included. Descriptive statistics were used. RESULTS: Of 994 ICU admissions with TBI in the study period, 182 had an initial Glasgow Coma Scale <13 and a length of stay in the ICU >48 hours. For 174 of them, a 6-month outcome assessment based on the Glasgow Outcome Scale (GOS) was available: 43.1% (36.0%-50.5%) had favorable outcomes (GOS 4 or 5), 28.7% (22.5%-35.9%) a severe disability (GOS 3), 0.6% (0%-3.2%) a vegetative state (GOS 2), and 27.6% (21.5%-34.7%) died (GOS 1). Among the GOS 1 individuals, 45 patients had a complete dataset (73% men; median age, 67 years; interquartile range, 43-79 years). Life-prolonging therapies were limited in 95.6% (85.2%-99.2%) of the cases after interdisciplinary prognostication and involvement of the surrogate decision maker (SDM) to respect the patient's documented or presumed will. In 97.7% (87.9%-99.9%) of the cases, a next of kin was the SDM and was involved in the EOL decision and process in 100% (96.3%-100.0%) of the cases. Written advance directives (ADs) were available for 14.0% (6.6%-27.3%) of the patients, and 34.9% (22.4%-49.8%) of the patients had shared their EOL will with relatives before trauma. In the other cases, each patient's presumed will was acknowledged after a meeting with the SDM and was binding for the EOL decision. CONCLUSIONS: At our institution, the majority of deaths after TBI follow a decision to limit life-prolonging therapies. The frequency of patients in vegetative state 6 months after TBI is lower than expected; this could be due to the high prevalence of limitation of life-prolonging therapies. EOL decision making follows a standardized process, based on patients' will documented in the ADs or on preferences assumed by the SDM. The prevalence of ADs was low and should be encouraged.

Body temperature affects cerebral hemodynamics in acutely brain injured patients: an observational transcranial color-coded duplex sonography study.

INTRODUCTION: Temperature changes are common in patients in a neurosurgical intensive care unit (NICU): fever is frequent among severe cases and hypothermia is used after cardiac arrest and is currently being tested in clinical trials to lower intracranial pressure (ICP). This study investigated cerebral hemodynamics when body temperature varies in acute brain injured patients. METHODS: We enrolled 26 patients, 14 with acute brain injury who developed fever and were given antipyretic therapy (defervescence group) and 12 who underwent an intracranial neurosurgical procedure and developed hypothermia in the operating room; once admitted to the NICU, still under anesthesia, they were re-warmed before waking (re-warming group). We measured cerebral blood flow velocity (CBF-V) and pulsatility index (PI) at the middle cerebral artery using transcranial color-coded duplex sonography (TCCDS). RESULTS: In the defervescence group mean CBF-V decreased from 75 ± 26 (95% CI 65 to 85) to 70 ± 22 cm/s (95% CI 61 to 79) (P = 0.04); the PI also fell, from 1.36 ± 0.33 (95% CI 1.23 to 1.50) to 1.16 ± 0.26 (95% CI 1.05 to 1.26) (P = 0.0005). In the subset of patients with ICP monitoring, ICP dropped from 16 ± 8 to 12 ± 6 mmHg (P = 0.003). In the re-warming group mean CBF-V increased from 36 ± 10 (95% CI 31 to 41) to 39 ± 13 (95% CI 33 to 45) cm/s (P = 0.04); the PI rose from 0.98 ± 0.14 (95% CI 0.91 to 1.04) to 1.09 ± 0.22 (95% CI 0.98 to 1.19) (P = 0.02). CONCLUSIONS: Body temperature affects cerebral hemodynamics as evaluated by TCCDS; when temperature rises, CBF-V increases in parallel, and viceversa when temperature decreases. When cerebral compliance is reduced and compensation mechanisms are exhausted, even modest temperature changes can greatly affect ICP.