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BackgroundTo ensure adequate intensive care unit (ICU) capacity for SARS-CoV-2 patients, elective neurosurgery and neurosurgical ICU capacity were reduced. Further, the Finnish government enforced strict restrictions to reduce the spread. Our objective was to assess changes in ICU admissions and prognosis of traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) during the Covid-19 pandemic.MethodsRetrospective review of all consecutive patients with TBI and aneurysmal SAH admitted to the neurosurgical ICU in Helsinki from January to May of 2019 and the same months of 2020. The pre-pandemic time was defined as weeks 1–11, and the pandemic time was defined as weeks 12–22. The number of admissions and standardized mortality rates (SMRs) were compared to assess the effect of the Covid-19 pandemic on these. Standardized mortality rates were adjusted for case mix.ResultsTwo hundred twenty-four patients were included (TBI n = 123, SAH n = 101). There were no notable differences in case mix between TBI and SAH patients admitted during the Covid-19 pandemic compared with before the pandemic. No notable difference in TBI or SAH ICU admissions during the pandemic was noted in comparison with early 2020 or 2019. SMRs were no higher during the pandemic than before.ConclusionIn the area of Helsinki, Finland, there were no changes in the number of ICU admissions or in prognosis of patients with TBI or SAH during the Covid-19 pandemic.

BackgroundCoagulopathy after traumatic brain injury (TBI) is associated with poor prognosis.PurposeTo assess the prevalence and association with outcomes of early thrombocytopenia in patients with TBI treated in the intensive care unit (ICU).MethodsThis is a retrospective multicenter study of adult TBI patients admitted to ICUs during 2003–2019. Thrombocytopenia was defined as a platelet count < 100 × 109/L during the first day. The association between thrombocytopenia and hospital and 12-month mortality was tested using multivariable logistic regression, adjusting for markers of injury severity.ResultsOf 4419 patients, 530 (12%) had early thrombocytopenia. In patients with thrombocytopenia, hospital and 12-month mortality were 26% and 48%, respectively; in patients with a platelet count > 100 × 109/L, they were 9% and 22%, respectively. After adjusting for injury severity, a higher platelet count was associated with decreased odds of hospital mortality (OR 0.998 per unit, 95% CI 0.996–0.999) and 12-month mortality (OR 0.998 per unit, 95% CI 0.997–0.999) in patients with moderate-to-severe TBI. Compared to patients with a normal platelet count, patients with thrombocytopenia not receiving platelet transfusion had an increased risk of 12-month mortality (OR 2.2, 95% CI 1.6–3.0), whereas patients with thrombocytopenia receiving platelet transfusion did not (OR 1.0, 95% CI 0.6–1.7).ConclusionEarly thrombocytopenia occurs in approximately one-tenth of patients with TBI treated in the ICU, and it is an independent risk factor for mortality in patients with moderate-to-severe TBI. Further research is necessary to determine whether this is modifiable by platelet transfusion.

Abstract BackgroundThere is increasing evidence that inflammation plays a role in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH) and in the development of delayed cerebral ischemia (DCI). However, the assessment and interpretation of classically defined inflammatory parameters is difficult in aSAH patients. The objective of this study was to investigate the relationship between easily assessable findings (hyperventilation, fever, white blood cell count (WBC), and C-reactive protein (CRP)) and the occurrence of DCI and unfavorable neurological outcome at discharge in aSAH patients.MethodsRetrospective analysis of prospectively collected data from a single center cohort. We evaluated the potential of clinical signs of inflammation (hyperventilation, fever) and simple inflammatory laboratory parameters CRP and WBC to predict unfavorable outcomes at discharge and DCI in a multivariate analysis. A cutoff value for CRP was calculated by Youden’s J statistic. Outcome was measured using the modified Rankin score at discharge, with an unfavorable outcome defined as modified Rankin scale (mRS) > 3.ResultsWe included 97 consecutive aSAH patients (63 females, 34 males, mean age 58 years) in the analysis. Twenty-one (22%) had major disability or died by the time of hospital discharge. Among inflammatory parameters, CRP over 100 mg/dl on day 2 was an independent predictor for worse neurological outcome at discharge. The average C-reactive protein level in the first 14 days was higher in patients with a worse neurological outcome (96.6, SD 48.3 vs 56.3 mg/dl, SD 28.6) in the first 14 days after aSAH. C-reactive protein on day 2 was an indicator of worse neurological outcome. No inflammatory parameter was an independent predictor of DCI. After multivariate adjustment, DCI, increased age, and more than 1 day of mechanical ventilation were significant predictors of worse neurological outcome.ConclusionsEarly elevated CRP levels were a significant predictor of worse neurological outcome at hospital discharge and may be a useful marker of later deterioration in aSAH.

Background Cerebral ischemia and neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) are major contributors to poor neurological outcome. Our study set out to investigate in an exploratory approach the interaction between NO and energy metabolism following SAH as both hypoxia and inflammation are known to affect nitric oxide (NO) metabolism and NO in turn affects mitochondria. Methods In seven patients under continuous multimodality neuromonitoring suffering poor-grade aneurysmal SAH, cerebral metabolism and NO levels (determined as a sum of nitrite plus nitrate) were determined in cerebral microdialysate for 14 days following SAH. In additional ex vivo experiments, rat cortex homogenate was subjected to the NO concentrations determined in SAH patients to test whether these NO concentrations impair mitochondrial function (determined by means of high-resolution respirometry). Results NO levels showed biphasic kinetics with drastically increased levels during the first 7 days (74.5 ± 29.9 μM) and significantly lower levels thereafter (47.5 ± 18.7 μM; p = 0.02). Only during the first 7 days, NO levels showed a strong negative correlation with brain tissue oxygen tension ( r = − 0.78; p < 0.001) and a positive correlation with cerebral lactate ( r = 0.79; p < 0.001), pyruvate ( r = 0.68; p < 0.001), glutamate ( r = 0.65; p < 0.001), as well as the lactate-pyruvate ratio ( r = 0.48; p = 0.01), suggesting mitochondrial dysfunction. Ex vivo experiments confirmed that the increase in NO levels determined in patients during the acute phase is sufficient to impair mitochondrial function ( p < 0.001). Mitochondrial respiration was inhibited irrespectively of whether glutamate (substrate of complex I) or succinate (substrate of complex II) was used as mitochondrial substrate suggesting the inhibition of mitochondrial complex IV. The latter was confirmed by direct determination of complex IV activity. Conclusions Exploratory analysis of our data suggests that during the acute phase of SAH, NO plays a key role in the neuronal damage impairing mitochondrial function and facilitating accumulation of mitochondrial substrate; further studies are required to understand mechanisms underlying this observation.

Abstract BackgroundSex-related differences in patients with aneurysmal subarachnoid hemorrhage (aSAH) exist. More females than males are affected. Aneurysm location is associated to sex. The relationship between sex and outcome, however, is unclear. Possible differences in management might influence the occurrence of primary and secondary brain injury and thus outcome. The study compares demographics, intensity of treatment, complications, and outcome among females and males with aSAH.MethodsAll consecutive patients with aSAH admitted to the neurocritical care unit, University Hospital Zurich over a 5-year period were eligible in this retrospective study. Patients’ characteristics, comorbidities, aSAH severity, frequency of vasospasm/delayed cerebral ischemia, frequency of invasive interventions, and 3-month outcome were compared by sex. Univariate analysis was performed with the data dichotomized by sex, and outcome. Multivariate analysis for prediction of outcomes was performed.ResultsThree hundred forty-eight patients were enrolled (64% females). Women were older than men. Comorbidities, scores at admission, and treatment modality were comparable among males and females. Vasospasm and DCI occurred similarly among females and males. Interventions and frequency of intraarterial spasmolysis were comparable between sexes. In the multivariate analysis, increasing age, female sex, increasing comorbidities, WFNS and Fisher grade, and presence of delayed cerebral ischemia were predictors of unfavorable outcome when considering all patients. However, after excluding death as a possible outcome, sex did not remain a predictor of unfavorable outcome.ConclusionsIn the study population, women with aSAH might have present a worse outcome at 3 months. However, no differences by sex that might explain this difference were found in intensity of treatment and management.

Background It is suspected that microbiome-derived trimethylamine N-oxide (TMAO) may enhance platelet responsiveness and accordingly be thrombophilic. The purpose of this prospective observational study is to evaluate TMAO in patients with subarachnoid hemorrhage (SAH) and compare it with a control group. A secondary aim was to investigate TMAO in the cerebrospinal fluid (CSF) from SAH patients. This should provide a better understanding of the role of TMAO in the pathogenesis of SAH and its thrombotic complications. Methods The study included patients with diagnosed spontaneous SAH recruited after initial treatment on admission and patients with nerve, nerve root, or plexus disorders serving as controls. Blood samples were gathered from all patients at recruitment. Additionally, sampling of SAH patients in the intensive care unit continued daily for 14 days. The CSF was collected out of existing external ventricular drains whenever possible. Results Thirty-four patients diagnosed with SAH, and 108 control patients participated in this study. Plasma TMAO levels at baseline were significantly lower in the SAH group (1.7 μmol/L) compared to the control group (2.9 μmol/L). TMAO was detectable in the CSF (0.4 μmol/L) and significantly lower than in plasma samples of the SAH group at baseline. Plasma and CSF TMAO levels correlated positively. The TMAO levels did not differ significantly during the observation period of 15 days. Conclusions Although we assumed that patients with higher TMAO levels were at higher risk for SAH a priori, plasma TMAO levels were lower in patients with SAH compared with control subjects with nerve, nerve root, or plexus disorders on admission to the hospital. A characteristic pattern of plasma TMAO levels in patients with SAH was not found.

Background The pulse waveform of intracranial pressure (ICP) is its distinctive feature almost always present in the clinical recordings. In most cases, it changes proportionally to rising ICP, and observation of these changes may be clinically useful. We introduce the higher harmonics centroid (HHC) which can be defined as the center of mass of harmonics of the ICP pulse waveform from the 2nd to 10th, where mass corresponds to amplitudes of these harmonics. We investigate the changes in HHC during ICP monitoring, including isolated episodes of ICP plateau waves. Material and methods Recordings from 325 patients treated between 2002 and 2010 were reviewed. Twenty-six patients with ICP plateau waves were identified. In the first step, the correlation between HHC and ICP was examined for the entire monitoring period. In the second step, the above relation was calculated separately for periods of elevated ICP during plateau wave and the baseline. Results For the values averaged over the whole monitoring period, ICP (22.3 ± 6.9 mm Hg) correlates significantly ( R  = 0.45, p  = 0.022) with HHC (3.64 ± 0.46). During the ICP plateau waves (ICP increased from 20.9 ± 6.0 to 53.7 ± 9.7 mm Hg, p  < 10 −16 ), we found a significant decrease in HHC (from 3.65 ± 0.48 to 3.21 ± 0.33, p  = 10 −5 ). Conclusions The good correlation between HHC and ICP supports the clinical application of pressure waveform analysis in addition to the recording of ICP number only. Mean ICP may be distorted by a zero drift, but HHC remains immune to this error. Further research is required to test whether a decline in HHC with elevated ICP can be an early warning sign of intracranial hypertension, whether individual breakpoints of correlation between ICP and its centroid are of clinical importance.

Background The mean age of actively treated subarachnoid hemorrhage (SAH) patients is increasing. We aimed to compare outcomes and prognostic factors between older and younger SAH patients. Methods A retrospective single-center analysis of aneurysmal SAH patients admitted to a neuro-ICU during 2014–2019. We defined older patients as ≥70 years and younger patients as <70 years. For every older patient, we identified three younger patients with the same World Federation of Neurological Surgeons (WFNS) grade. We only included patients receiving active aneurysm treatment. Favorable functional outcome, defined as a Glasgow Outcome Scale (GOS) of 4–5 at 12 months, was our primary outcome. We used logistic regression to compare prognostic factors between the groups. Results Ninety-five (85%) of 112 older patients and 317 (94%) of 336 younger patients received aneurysm treatment. Of the younger patients, 91% with a good-grade SAH (WFNS I-III) had a favorable outcome compared to 52% in the older good-grade SAH group. In poor-grade patients (WFNS IV-V), favorable outcome was seen in 51% of younger patients, compared to 24% of older patients. Acute hydrocephalus and intracerebral hemorrhage were associated with unfavorable outcome in the younger (OR 4.7, 95% CI 2.6–8.4, and OR 3.7, 95% CI 2.1–6.4), but not in the older patients (OR 1.8, 95% CI 0.8–4.2, and OR 1.3, 95% CI 0.5–3.1, respectively). Conclusions In actively treated SAH patients, age was a major determinant of outcome. Factors reflecting increases in intracranial pressure associated with outcome only among younger patients.

BackgroundMechanical 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.MethodsPatients 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.ResultsA 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.ConclusionsThe 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.

BackgroundPostoperative opioid use plays an important role in the global opioid crisis, but little is known about in-hospital opioid use trends of large surgical units. We investigated whether postoperative in-hospital opioid consumption changed in a large academic neurosurgical unit between 2007 and 2018.MethodsWe extracted the data of consumed opioids in the neurosurgical intensive care unit and two bed wards between 2007 and 2018. Besides overall consumption, we analyzed the trends for weak (tramadol and codeine), strong, and the most commonly used opioids. The use of various opioids was standardized using the defined daily doses (DDDs) of each opioid agent. A linear regression analysis was performed to estimate annual treatment day-adjusted changes with 95% confidence intervals.ResultsOverall, 121 361 opioid DDDs were consumed during the 196 199 treatment days. Oxycodone was the most commonly used postoperative opioid (49% of all used opioids) in neurosurgery. In the bed wards, the use of oral oxycodone increased 375% (on average 13% (9–17%) per year), and the use of transdermal buprenorphine 930% (on average 26% (9–45%) per year) over the 12-year period. Despite the increased use of strong opioids in the bed wards (on average 3% (1–4%) per year), overall opioid use decreased 39% (on average 6% (4–7%) per year) between 2007 and 2018.ConclusionsDue to the increase of strong opioid use in the surgical bed wards, we encourage other large teaching hospitals and surgical units to investigate whether their opioid use trends are similarly worrisome and whether the opioid consumption changes in the hospital setting are transferred to opioid use patterns or opioid-related harms after discharge.