Purpose of Review
Over the last years, the focus of clinical and animal research in subarachnoid hemorrhage (SAH) shifted towards the early phase after the bleeding based on the association of the ...early injury pattern (first 72 h) with secondary complications and poor outcome. This phase is commonly referenced as early brain injury (EBI). In this clinical review, we intended to overview commonly used definitions of EBI, underlying mechanisms, and potential treatment implications.
Recent Findings
We found a large heterogeneity in the definition used for EBI comprising clinical symptoms, neuroimaging parameters, and advanced neuromonitoring techniques. Although specific treatments are currently not available, therapeutic interventions are aimed at ameliorating EBI by improving the energy/supply mismatch in the early phase after SAH.
Summary
Future research integrating brain-derived biomarkers is warranted to improve our pathophysiologic understanding of EBI in order to ameliorate early injury patterns and improve patients’ outcomes.
Lumbar puncture (LP) is recommended in patients with thunderclap headache and negative computed tomography to rule out spontaneous subarachnoid haemorrhage (SAH). Blood contamination of cerebrospinal ...fluid (CSF) due to traumatic LP poses a diagnostic dilemma. Therefore, routine CSF parameters were investigated to distinguish between SAH and a traumatic LP. CSF red blood cell (RBC), white blood cell (WBC) count, total protein, CSF colour and supernatant were used for group comparisons of patients with SAH and 'symptomatic controls'. Due to variable time intervals between bleeding onset and LP in SAH patients in contrast to patients with traumatic LP, where blood contamination of CSF occurs at the time of LP, CSF variables were adjusted for decay in time to allow comparability. Logistic regression analysis identified bloody CSF odds ratio (OR) 32.6, xanthochromic supernatant OR 15.5 and WBC
OR 4.5 (per increase of 100/µl) as predictors of SAH, while age, sex and CSF total protein
were no predictors. Optimal cut-point of RBC
(determined at day 1 after bleeding) was > 3667/µl to identify SAH patients with a 97% sensitivity and 94% specificity. Combination of low RBC and clear CSF supernatant was found in none of SAH patients. Combined CSF RBC count and CSF supernatant reliably distinguished traumatic LP from SAH.
Subarachnoid hemorrhage is a life-threatening disease associated with high mortality and morbidity. A substantial number of patients develop systemic inflammatory response syndrome. We aimed to ...identify risk factors for systemic inflammatory response syndrome development and to evaluate the role of systemic inflammatory response syndrome on patients' outcome.
Retrospective observational cohort study of prospectively collected data.
Neurocritical care unit at a tertiary academic medical center.
Two-hundred and ninety-seven consecutive nontraumatic subarachnoid hemorrhage patients admitted to the neurologic ICU between 2010 and 2017.
Systemic inflammatory response syndrome was diagnosed based on greater than or equal to two criteria (hypo-/hyperthermia, tachypnea, leukopenia/leukocytosis, tachycardia) and defined as early (≤ 3 d) and delayed (days 6-10) systemic inflammatory response syndrome burden (systemic inflammatory response syndrome positive days within the first 10 d). Using multivariate analysis, risk factors for the development of early and delayed systemic inflammatory response syndrome and the relationship of systemic inflammatory response syndrome with poor 3-month functional outcome (modified Rankin Scale score ≥ 3) were analyzed.
Seventy-eight percent of subarachnoid hemorrhage patients had early systemic inflammatory response syndrome, and 69% developed delayed systemic inflammatory response syndrome. Median systemic inflammatory response syndrome burden was 60% (interquartile range, 10-90%). Risk factors for early systemic inflammatory response syndrome were higher admission Hunt and Hess grade (odds ratio, 1.75; 95% CI, 1.09-2.83; p = 0.02), aneurysm clipping (odds ratio, 4.84; 95% CI, 1.02-23.05; p = 0.048), and higher modified Fisher Scale score (odds ratio, 1.88; 95% CI, 1.25-2.89; p = 0.003). Hunt and Hess grade and pneumonia were independently associated with delayed systemic inflammatory response syndrome development. Systemic inflammatory response syndrome burden (area under the curve, 0.84; 95% CI, 0.79-0.88) had a higher predictive value for 3-month poor outcome compared with early systemic inflammatory response syndrome (area under the curve, 0.76; 95% CI, 0.70-0.81; p < 0.001).
Systemic inflammatory response syndrome is common after subarachnoid hemorrhage and independently contributes to poor functional outcome. Systemic inflammatory response syndrome burden more accurately predicts poor outcome than early systemic inflammatory response syndrome.
Purpose
To assess patient characteristics associated with health-related quality of life (HR-QoL) and its mental and physical subcategories 3 months after diagnosis with COVID-19.
Methods
In this ...prospective multicentre cohort study, HR-QoL was assessed in 90 patients using the SF-36 questionnaire (36-item Short Form Health Survey), which consists of 8 health domains that can be divided into a mental and physical health component. Mental health symptoms including anxiety, depression, and post-traumatic stress disorders were evaluated using the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Stress Disorder Checklist-5 (PCL-5) 3 months after COVID-19. Using descriptive statistics and multivariable regression analysis, we identified factors associated with impaired HR-QoL 3 months after COVID-19 diagnosis.
Results
Patients were 55 years of age (IQR, 49–63; 39% women) and were classified as severe (23%), moderate (57%), or mild (20%) according to acute disease severity. HR-QoL was impaired in 28/90 patients (31%). Younger age per year, adjOR (95%CI) 0.94 (0.88–1.00),
p
= 0.049, longer hospitalization per day, adjOR (95%CI) 1.07 (1.01–1.13),
p
= 0.015, impaired sleep adjOR (95%CI) 5.54 (1.2–25.61),
p
= 0.028, and anxiety adjOR (95%CI) 15.67 (3.03–80.99),
p
= 0.001) were independently associated with impaired HR-QoL. Twenty-nine percent (
n
= 26) scored below the normal range on the mental health component of the SF-36 and independent associations emerged for anxiety, depression, and self-reported numbness. Impairments in the physical health component of the SF-36 were reported by 12 (13%) patients and linked to hypogeusia and fatigue.
Conclusion
Every third patient reported a reduction in HR-QoL 3 months after COVID-19 diagnosis and impairments were more prominent in mental than physical well-being.
Delayed cerebral ischaemia (DCI) complicates the clinical course of patients with subarachnoid haemorrhage (SAH) in 20--30% and substantially worsens outcome. In this review, we describe a multimodal ...diagnostic approach based on underlying mechanisms of DCI and provide treatment options with a special focus on the most recently published literature.
Symptomatic vasospasm refers to clinical deterioration in the presence of vasospasm whereas DCI constitutes multiple causes. Pathophysiologic mechanisms underlying DCI range beyond large vessel vasospasm from neuroinflammation, to microthromboembolism, impaired cerebral autoregulation, cortical spreading depolarizations and many others. The current definition of DCI can be challenged by these mechanisms. We propose a pragmatic approach using a combination of clinical examination, cerebral ultrasonography, neuroimaging modalities and multimodal neuromonitoring to trigger therapeutic interventions in the presence of DCI. In addition to prophylactic nimodipine and management principles to improve oxygen delivery and decrease the brain metabolic demand, other specific interventions include permissive hypertension, intra-arterial application of calcium channel blockers and in selected patients angioplasty.
The complex pathophysiology underlying DCI urges for a multimodal diagnostic approach triggering targeted interventions. Novel treatment concepts still have to be proven in large trials.
To review the published literature on the clinical application of cerebral microdialysis (CMD) in aneurysmal subarachnoid hemorrhage (SAH) patients and to summarize the evidence relating cerebral ...metabolism to pathophysiology, secondary brain injury, and outcome.
: Two reviewers identified all manuscripts reporting on the clinical use of CMD in aneurysmal SAH patients from MEDLINE. All identified studies were grouped according to their focus on brain metabolic changes during the early and subacute phase after SAH, their association with mechanisms of secondary brain injury and outcome.
The review demonstrated: (1) limited literature is available in the very early phase before the aneurysm is secured. (2) Brain metabolic changes related to early and delayed secondary injury mechanisms may be used in addition to other neuromonitoring parameters in the critical care management of SAH patients. (3) CMD markers of ischemia may detect delayed cerebral ischemia early (up to 16 h before onset), underlining the importance of trend analysis. (4) Various CMD-derived parameters may be associated with patient outcome at 3-12 months, including CMD-lactate-to-pyruvate-ratio, CMD-glucose, and CMD-glutamate.
The clinical use of CMD is an emerging area in the literature of aneurysmal SAH patients. Larger prospective multi-center studies on interventions based on CMD findings are needed.
Enteral nutrition (EN) often fails to achieve nutritional goals in neurocritical care patients. We sought to investigate the safety and utility of supplemental parenteral nutrition (PN) in ...subarachnoid hemorrhage (SAH) patients.
Data of 70 consecutive patients with non-traumatic SAH admitted to the neurological intensive care unit of a tertiary referral center were prospectively collected and retrospectively analyzed. We targeted the provision of 20-25 kilocalories per kilogram bodyweight per day (kcal/kg/d) by enteral nutrition. Supplemental PN was given when this target could not be reached. Nutritional data were analyzed for up to 14 days of ICU stay. Hospital complications were tested for associations with impaired enteral feeding. The amounts of EN and PN were tested for associations with the level of protein delivery and functional outcome. Repeated measurements within subjects were handled utilizing generalized estimating equations.
Forty (27 women and 13 men) of 70 screened patients were eligible for the analysis. Median age was 61 (IQR 49-71) years, 8 patients (20%) died in the hospital. Thirty-six patients (90%) received PN for a median duration of 8 (IQR 4-12) days. The provision of 20 kcal/kg by EN on at least 1 day of ICU stay was only achieved in 24 patients (60%). Hydrocephalus (p = 0.020), pneumonia (p = 0.037) and sepsis (p = 0.013) were associated with impaired enteral feeding. Neither the amount nor the duration of PN administration was associated with an increased risk of severe complications or poor outcome. Supplemental PN was associated with significantly increased protein delivery (p<0.001). In patients with sepsis or pneumonia, there was an association between higher protein delivery and good functional outcome (p<0.001 and p = 0.031), but not in the overall cohort (p = 0.08).
Enteral feeding was insufficient to achieve nutritional goals in subarachnoid hemorrhage patients. Supplemental PN was safe and associated with increased protein delivery. A higher protein supply was associated with good functional outcome in patients who developed sepsis or pneumonia.
The amino-acids tryptophan, phenylalanine and tyrosine seem to play an important role in the pathophysiology of depressive disorders. We measured daily brain extracellular levels of these amino-acids ...using cerebral microdialysis (CMD) and high performance liquid chromatography in 26 consecutive subarachnoid hemorrhage (SAH) patients and associated them with the presence of depressive disorders. Patients were grouped as follows: medical history of depression (prior to SAH), antidepressant intake 12 months after SAH (but not before), or neither. CMD-tryptophan, CMD-phenylalanine and CMD-tyrosine levels were significantly lower in patients with preexisting depressive disorders compared to those without depression (p < 0.01). Disease severity and SAH-related complications were not associated with amino-acid concentrations. We found a positive correlation between nutritionally administered and brain interstitial levels of tryptophan and phenylalanine in non-depressed patients (R = 0.26 and R = 0.24, p < 0.05), which was not present in patients with preexisting depression (p > 0.1). In conclusion, brain interstitial levels of tryptophan, phenylalanine and tyrosine measured in the context of the clinical management of SAH were significantly decreased in patients with a medical history of depression. This study supports the hypothesis that the availability of these neurotransmitter precursor amino-acids in the human brain may play an important role in the pathophysiology of depressive disorders.
Background
Spontaneous subarachnoid hemorrhage (SAH) is a severe neurological disease that frequently requires placement of external ventricular drainage (EVD). Cerebrospinal fluid (CSF) obtained
via
...the drain is used to detect potential complications of SAH.
Objective
This study aimed to describe the longitudinal profile of routine CSF parameters in patients with SAH and to identify associations with neurological complications.
Methods
A total of thirty-three patients with spontaneous SAH who required an EVD and had at least three consecutive CSF samples collected over a period of more than 7 days were included in this study.
Results
A median of 6 longitudinally collected CSF samples per patient were available within 1–22 days after SAH onset. Overall, red blood cells (RBC) steadily decreased over time, whereas white blood cells (WBC) and total protein (TP) increased until days 6 and 13, respectively, and decreased thereafter. The estimated decay rates of RBC, WBC, and TP were 28, 22, and 6% per day. Distinct CSF patterns over time were linked to known complications after SAH. Patients with rebleeding showed increased RBC, TP, and phagocytosing cells compared to patients without re-bleeding. For ventriculitis, an elevated cell index with a higher proportion of granulocytes was characteristic. CSF of patients with delayed cerebral ischemia showed increased RBC and WBC compared to patients without DCI. Early CSF WBC and cell index were predictive for the occurrence of DCI and ventriculitis later during the disease course. The amount of daily CSF drainage
via
EVD had no impact on routine CSF parameters.
Conclusion
Longitudinal CSF characteristics are associated with SAH-related complications.
Background
Fluid management in patients after subarachnoid hemorrhage (SAH) aims at the optimization of cerebral blood flow and brain oxygenation. In this study, we investigated the effects of ...hemodynamic management on brain oxygenation by integrating advanced hemodynamic and invasive neuromonitoring.
Methods
This observational cohort bi-center study included data of consecutive poor-grade SAH patients who underwent pulse contour cardiac output (PiCCO) monitoring and invasive neuromonitoring. Fluid management was guided by the transpulmonary thermodilution system and aimed at euvolemia (cardiac index, CI ≥ 3.0 L/min/m
2
; global end-diastolic index, GEDI 680–800 mL/m
2
; stroke volume variation, SVV < 10%). Patients were managed using a brain tissue oxygenation (P
bt
O
2
) targeted protocol to prevent brain tissue hypoxia (BTH, P
bt
O
2
< 20 mmHg). To assess the association between CI and P
bt
O
2
and the effect of fluid challenges on CI and P
bt
O
2
, we used generalized estimating equations to account for repeated measurements.
Results
Among a total of 60 included patients (median age 56 IQRs 47–65 years), BTH occurred in 23% of the monitoring time during the first 10 days since admission. Overall, mean CI was within normal ranges (ranging from 3.1 ± 1.3 on day 0 to 4.1 ± 1.1 L/min/m
2
on day 4). Higher CI levels were associated with higher P
bt
O
2
levels (Wald = 14.2;
p
< 0.001). Neither daily fluid input nor fluid balance was associated with absolute P
bt
O
2
levels (
p
= 0.94 and
p
= 0.85, respectively) or the occurrence of BTH (
p
= 0.68 and
p
= 0.71, respectively). P
bt
O
2
levels were not significantly different in preload dependent patients compared to episodes of euvolemia. P
bt
O
2
increased as a response to fluid boluses only if BTH was present at baseline (from 13 ± 6 to 16 ± 11 mmHg, OR = 13.3 95% CI 2.6–67.4,
p
= 0.002), but not when all boluses were considered (
p
= 0.154).
Conclusions
In this study a moderate association between increased cardiac output and brain oxygenation was observed. Fluid challenges may improve P
bt
O
2
only in the presence of baseline BTH. Individualized hemodynamic management requires advanced cardiac and brain monitoring in critically ill SAH patients.
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