Hannes Lücking

Hyponatremia Is an Independent Predictor of In-Hospital Mortality in Spontaneous Intracerebral Hemorrhage

Background and Purpose— Hyponatremia is the most frequent electrolyte disturbance in critical care. Across various disciplines, hyponatremia is associated with increased mortality and longer hospital stay, yet in intracerebral hemorrhage (ICH) no data are available. This the first study that investigated the prevalence and clinical associations of hyponatremia in patients with ICH. Methods— This observational study included all consecutive spontaneous ICH patients (n=464) admitted during a 5-year period to the Department of Neurology. Patient characteristics, in-hospital measures, mortality, and functional outcome (90 days and 1 year) were analyzed to determine the effects of hyponatremia (Na <135 mEq/L). Multivariable regression analyses were calculated for factors associated with hyponatremia and predictors of in-hospital mortality. Results— The prevalence of hyponatremia on hospital admission was 15.6% (n=66). Normonatremia was achieved and maintained in almost all hyponatremia patients <48 hours. In-hospital mortality was roughly doubled in hyponatremia compared with nonhyponatremia patients (40.9%; n=27 versus 21.1%; n=75), translating into a 2.5-fold increased odds ratio (P<0.001). Multivariable analyses identified hyponatremia as an independent predictor of in-hospital mortality (odds ratio, 2.2; 95% confidence interval, 1.05–4.62; P=0.037). Within 90 days after ICH, hyponatremia patients surviving hospital stay were also at greater risk of death (odds ratio, 4.8; 95% confidence interval, 2.1–10.6; P<0.001); thereafter, mortality rates were similar. Conclusions— Hyponatremia was identified as an independent predictor of in-hospital mortality with a fairly high prevalence in spontaneous ICH patients. The presence of hyponatremia at hospital admission is related to an increased short-term mortality in patients surviving acute care, possibly reflecting a preexisting condition that is linked to worse outcome due to greater comorbidity. Correction of hyponatremia does not seem to compensate its influence on mortality, which strongly warrants future research.

Predictors for good functional outcome after neurocritical care

IntroductionThere are only limited data on the long-term outcome of patients receiving specialized neurocritical care. In this study we analyzed survival, long-term mortality and functional outcome after neurocritical care and determined predictors for good functional outcome.MethodsWe retrospectively investigated 796 consecutive patients admitted to a non-surgical neurologic intensive care unit over a period of two years (2006 and 2007). Demographic and clinical parameters were analyzed. Depending on the diagnosis, we grouped patients according to their diseases (cerebral ischemia, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), meningitis/encephalitis, epilepsy, Guillain-Barré syndrome (GBS) and myasthenia gravis (MG), neurodegenerative diseases and encephalopathy, cerebral neoplasm and intoxication). Clinical parameters, mortality and functional outcome of all treated patients were analyzed. Functional outcome (using the modified Rankin Scale, mRS) one year after discharge was assessed by a mailed questionnaire or telephone interview. Outcome was dichotomized into good (mRS ≤ 2) and poor (mRS ≥ 3). Logistic regression analyses were calculated to determine independent predictors for good functional outcome.ResultsOverall in-hospital mortality amounted to 22.5% of all patients, and a good long-term functional outcome was achieved in 28.4%. The parameters age, length of ventilation (LOV), admission diagnosis of ICH, GBS/MG, and inoperable cerebral neoplasm as well as Therapeutic Intervention Scoring System (TISS)-28 on Day 1 were independently associated with functional outcome after one year.ConclusionsThis investigation revealed that age, LOV and TISS-28 on Day 1 were strongly predictive for the outcome. The diagnoses of hemorrhagic stroke and cerebral neoplasm leading to neurocritical care predispose for functional dependence or death, whereas patients with GBS and MG are more likely to recover after neurocritical care.

Anemia is an independent prognostic factor in intracerebral hemorrhage: an observational cohort study

IntroductionTo date only two studies have evaluated anemia status in acute intracerebral hemorrhage (ICH) reporting that on admission anemia (OAA) was associated with larger hematoma volume, and lower hemoglobin levels during hospital stay, which related to poorer outcome. The question remains whether anemia influences outcome through related volume-effects or itself has an independent impact?MethodsThis single-center investigation included 435 consecutive patients with spontaneous ICH admitted to the Department of Neurology over five years. Functional short- and long-term outcome (3 months and 1 year) were analyzed for anemia status. Multivariate logistic and graphical regression analyses were calculated for associations of anemia and to determine independent effects on functional outcome. It was decided to perform a separate analysis for patients with ICH-volume <30cm3 (minor-volume-ICH).ResultsOverall short-term-outcome was worse in anemic patients (mRS[4-6] OAA = 93.3% vs. non-OAA = 61.2%, P < 0.01), and there was a further shift towards an increased long-term mortality (P = 0.02). The probability of unfavorable long-term-outcome (mRS[4-6]) in OAA was elevated 7-fold (OR:7.5; P < 0.01). Receiver operating characteristics curve (ROC) analysis revealed a positive but poor association of ICH-volume and anemia (AUC = 0.67) suggesting volume-undriven outcome-effects of anemia (AUC = 0.75). Multivariate regression analyses revealed that anemia, besides established parameters, has the strongest relation to unfavorable outcome (OR:3.0; P < 0.01). This is even more pronounced in minor-volume-ICH (OR:5.6; P < 0.01).ConclusionsAnemia seems to be a previously unrecognized significant predictor of unfavorable functional outcome with independent effects beyond its association with larger hemorrhage volumes. The recognition of anemia and its treatment may possibly influence outcome after ICH and as such prospective interventional studies are warranted.

Optimized angiographic computed tomography with intravenous contrast injection: an alternative to conventional angiography in the follow-up of clipped aneurysms?

OBJECT The purpose of this study was to evaluate the diagnostic accuracy of an optimized angiographic CT (ACT) program with intravenous contrast agent injection (ivACT) in the assessment of potential aneurysm remnants after neurosurgical clipping compared with conventional digital subtraction angiography (DSA). METHODS The authors report on 14 patients with 19 surgically clipped cerebral aneurysms who were scheduled to undergo angiographic follow-up. For each patient, the authors performed ivACT with dual rotational acquisition and conventional angiography including a 3D rotational run. The ivACT and 3D DSA data were reconstructed with different imaging modes, including a newly implemented subtraction mode with motion correction. Thereafter, the data sets were merged by the dual-volume technique, and freely rotatable 3D images were obtained for further analysis. Observed aneurysm remnants were electronically measured and classified for each modality by 2 experienced neuroradiologists. RESULTS Digital subtraction angiography and ivACT both provided high-quality images without motion artifacts. Artifact disturbances from the aneurysm clips led to a compromised, but still sufficient, image quality in 1 case. The ivACT assessed all aneurysm remnants as true-positive up to a minimal size of 2.6×2.4 mm in accordance with the DSA findings. There was a tendency for ivACT to overestimate the size of the aneurysm remnants. All cases without aneurysm remnants on DSA were scored correctly as true-negative by ivACT. CONCLUSIONS By using an optimized image acquisition protocol as well as enhanced postprocessing algorithms, the noninvasive ivACT seems to achieve results comparable to those of conventional angiography in the follow-up of clipped cerebral aneurysms. The authors have shown that ivACT can provide reliable diagnostic information about potential aneurysm remnants after neurosurgical clipping with high sensitivity and specificity, sufficient for clinical decision making, at least for aneurysms in the anterior circulation located distal to the internal carotid artery. These preliminary results may be a promising step to replace conventional angiography by a noninvasive imaging technique in selected cases after aneurysm clipping.

Impact of Hypothermia Initiation and Duration on Perihemorrhagic Edema Evolution After Intracerebral Hemorrhage

Background and Purpose— Intracerebral hemorrhage (ICH) causes high morbidity and mortality. Recently, perihemorrhagic edema (PHE) has been suggested as an important prognostic factor. Therapeutic hypothermia may be a promising therapeutic option to treat PHE. However, no data exist about the optimal timing and duration of therapeutic hypothermia in ICH. We examined the impact of therapeutic hypothermia timing and duration on PHE evolution. Methods— In this retrospective, single-center, case–control study, we identified patients with ICH treated with mild endovascular hypothermia (target temperature 35°C) from our institutional database. Patients were grouped according to hypothermia initiation (early: days 1–2 and late: days 4–5 after admission) and hypothermia duration (short: 4–8 days and long: 9–15 days). Patients with ICH matched for ICH volume, age, ICH localization, and intraventricular hemorrhage were identified as controls. Relative PHE, temperature, and intracranial pressure course were analyzed. Clinical outcome on day 90 was assessed using the modified Rankin scale (0–3=favorable and 4–6=poor). Results— Thirty-three patients with ICH treated with hypothermia and 37 control patients were included. Early hypothermia initiation led to relative PHE decrease between admission and day 3, whereas median relative PHE increased in control patients (−0.05 [interquartile range, −0.4 to 0.07] and 0.07 [interquartile range, −0.07 to 0.26], respectively; P=0.007) and patients with late hypothermia initiation (0.22 [interquartile range 0.12–0.27]; P=0.037). After day 3, relative PHE increased in all groups without difference. Outcome was not different between patients treated with hypothermia and controls. Conclusions— Early hypothermia initiation after ICH onset seems to have an important impact on PHE evolution, whereas our data suggest only limited impact later than day 3 after onset.

Predictive Factors for Percutaneous Endoscopic Gastrostomy in Patients with Spontaneous Intracranial Hemorrhage

Background: Dysphagia is frequent after hemorrhagic stroke, and some of the affected patients require prolonged enteral nutrition, most often via percutaneous endoscopic gastrostomy (PEG) tubes. The identification of patients at risk of prolonged dysphagia permits earlier tube placement and helps guide clinicians in the decision-making process. Methods: This retrospective study included all patients with spontaneous ICH admitted to a tertiary university hospital from 2007 until 2009 (n = 208). Fifty-one patients received PEG tubes. PEG tube placement was conducted in ventilated patients within 30 days and in spontaneously breathing patients if swallowing did not improve within 14 days. Results: Twenty-five percent of patients received PEG tubes. Those patients had larger lobar hemorrhages, intraventricular hemorrhage and occlusive hydrocephalus and higher ICH scores. Furthermore, patients with PEG scored worse on Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS) and Acute Physiology And Chronic Health Evaluation (APACHE II), more frequently needed mechanical ventilation, and had more inflammatory and renal complications. A multivariate regression analysis identified GCS, occlusive hydrocephalus, mechanical ventilation, and systemic sepsis as independent risk factors for PEG tube placement. Conclusion: Disease severity and neurocritical care complications represent the major influencing parameters for PEG tube placement in spontaneous ICH patients.

Neutrophil-to-Lymphocyte Ratio Is an Independent Predictor for In-Hospital Mortality in Spontaneous Intracerebral Hemorrhage

Background and Purpose: Stroke-associated immunosuppression and inflammation are increasingly recognized as factors that trigger infections and thus, potentially influence the outcome after stroke. Several studies demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes in patients with ischemic stroke. However, little is known about the impact of NLR on short-term mortality in intracerebral hemorrhage (ICH). Methods: This observational study included 855 consecutive ICH-patients. Patient demographics, clinical, laboratory, and in-hospital measures as well as neuroradiological data were retrieved from institutional databases. Functional 3-months-outcome was assessed and categorized as favorable (modified Rankin Scale [mRS] 0-3) and unfavorable (mRS 4-6). We (i) studied the natural course of NLR in ICH, (ii) analyzed parameters associated with NLR on admission (NLROA), and (iii) evaluated the clinical impact of NLR on mortality and functional outcome. Results: The median NLROA of the entire cohort was 4.66 and it remained stable during the entire hospital stay. Patients with NLR ≥4.66 showed significant associations with poorer neurological status (National Institute of Health Stroke Scale [NIHSS] 18 [9-32] vs. 10 [4-21]; p < 0.001), larger hematoma volume on admission (17.6 [6.9-47.7] vs. 10.6 [3.8-31.7] mL; p = 0.001), and more frequently unfavorable outcome (mRS 4-6 at 3 months: 317/427 [74.2%] vs. 275/428 [64.3%]; p = 0.002). Patients with an NLR under the 25th percentile (NLR <2.606) - compared to patients with NLR >2.606 - presented with a better clinical status (NIHSS 12 [5-21] vs. 15 [6-28]; p = 0.005), lower hematoma volumes on admission (10.6 [3.6-30.1] vs. 15.1 [5.7-42.3] mL; p = 0.004) and showed a better functional outcome (3 months mRS 0-3: 82/214 [38.3%] vs. 185/641 [28.9%]; p = 0.009). Patients associated with high NLR (≥8.508 = above 75th-percentile) showed the worst neurological status on admission (NIHSS 21 [12-32] vs. 12 [5-23]; p < 0.001), larger hematoma volumes (21.0 [8.6-48.8] vs. 12.2 [4.1-34.9] mL; p < 0.001), and higher proportions of unfavorable functional outcome at 3 months (mRS 4-6: 173/214 vs. 418/641; p < 0.001). Further, NLR was linked to more frequently occurring infectious complications (pneumonia 107/214 vs. 240/641; p = 0.001, sepsis: 78/214 vs. 116/641; p < 0.001), and increased c-reactive-protein levels on admission (p < 0.001; R2 = 0.064). Adjusting for the above-mentioned baseline confounders, multivariable logistic analyses revealed independent associations of NLROA with in-hospital mortality (OR 0.967, 95% CI 0.939-0.997; p = 0.029). Conclusions: NLR represents an independent parameter associated with increased mortality in ICH patients. Stroke physicians should focus intensely on patients with increased NLR, as these patients appear to represent a population at risk for infectious complications and increased short-mortality. Whether these patients with elevated NLR may benefit from a close monitoring and specially designed therapies should be investigated in future studies.

Lymphocytopenia Is an Independent Predictor of Unfavorable Functional Outcome in Spontaneous Intracerebral Hemorrhage

Background and Purpose— Stroke-associated immunosuppression is an increasingly recognized factor triggering infections and thus potentially influencing outcome after stroke. Specifically, lymphocytopenia after intracerebral hemorrhage (ICH) has only been addressed in small-sized retrospective studies of mixed intracranial bleedings. This cohort study investigated the natural course of lymphocytopenia, parameters associated with lymphocytopenia on admission (LOA) and during stay, and evaluated the clinical impact of lymphocytopenia in solely ICH patients. Methods— This observational study included 855 consecutive patients with ICH. Patient demographics, clinical and neuroradiological data as well as laboratory and in-hospital measures were retrieved from institutional prospective databases. Functional 3-month outcome was assessed by mailed questionnaires. Lymphocytopenia was defined as <1.0 (109/L) and was correlated with patient’s characteristics and outcome. Results— Prevalence of LOA was 27.3%. Patients with LOA showed significant associations with poorer neurological status (18 [10–32] versus 13 [5–24]; P<0.001), larger hematoma volume (18.5 [6.2–46.2] versus 12.8 [4.4–37.8]; P=0.006), and unfavorable outcome (74.7% versus 63.3%; P=0.0018). Natural course of lymphocyte count during hospital stay revealed a lymphocyte nadir of 1.1 (0.80–1.53 [109/L]) at day 5. Focusing on patients with day-5-lymphocytopenia, compared with patients with LOA, revealed increased rates of infections (63 [71.6] versus 113 [48.5]; P<0.001) and poorer functional outcome at 3 months (76 [86.4] versus 175 [75.1); P=0.029). Adjusting for baseline confounders, multivariable logistic and receiver operating characteristics analyses documented independent associations of day-5-lymphocytopenia with unfavorable outcome (day-5-lymphocytopenia: odds ratio, 2.017 [95% confidence interval, 1.029–3.955], P=0.041; LOA: odds ratio, 1.391 [0.795–2.432], P=0.248; receiver operating characteristics: day-5-lymphocytopenia: area under the curve=0.673, P<0.0001, Youden’s index=0.290; LOA: area under the curve=0.513, P=0.676, Youden’s index=0.084), whereas receiver operating characteristics analyses revealed no association of age or hematoma volume with day-5-lymphocytopenia (age: area under the curve=0.540, P=0.198, Youden’s index=0.106; volume: area under the curve=0.550, P=0.0898, Youden’s index=0.1224). Conclusions— Lymphocytopenia is frequently present in patients with ICH and may represent an independent parameter associated with unfavorable functional outcome. Developing lymphocytopenia affected outcome even stronger than LOA, a finding that may open up new therapeutic avenues in specific subsets of patients with ICH.

Severity assessment in maximally treated ICH patients: The max-ICH score.

Objective: As common prognostication models in intracerebral hemorrhage (ICH) are developed variably including patients with early (<24 hours) care limitations (ECL), we investigated its interaction with prognostication in maximally treated patients and sought to provide a new unbiased severity assessment tool. Methods: This observational cohort study analyzed consecutive ICH patients (n = 583) from a prospective registry over 5 years. We characterized the influence of ECL on overall outcome by propensity score matching and on conventional prognostication using receiver operating characteristic analyses. We established the max-ICH score based on independent predictors of 12-month functional outcome in maximally treated patients and compared it to existing models. Results: Prevalence of ECL was 19.2% (n = 112/583) and all of these patients died. Yet propensity score matching displayed that 50.7% (n = 35/69) theoretically could have survived, with 18.8% (n = 13/69) possibly reaching favorable outcome (modified Rankin Scale score 0–3). Conventional prognostication seemed to be confounded by ECL, documented by a decreased predictive validity (area under the curve [AUC] 0.67, confidence interval [CI] 0.61–0.73 vs AUC 0.80, CI 0.76–0.83; p < 0.01), overestimating poor outcome (mortality by 44.8%, unfavorable outcome by 10.1%) in maximally treated patients. In these patients, the novel max-ICH score (0–10) integrates strength-adjusted predictors, i.e., NIH Stroke Scale score, age, intraventricular hemorrhage, anticoagulation, and ICH volume (lobar and nonlobar), demonstrating improved predictive accuracy for functional outcome (12 months: AUC 0.81, CI 0.77–0.85; p < 0.01). The max-ICH score may more accurately delineate potentials of aggressive care, showing favorable outcome in 45.4% (n = 214/471) and a long-term mortality rate of only 30.1% (n = 142/471). Conclusions: Care limitations significantly influenced the validity of common prognostication models resulting in overestimation of poor outcome. The max-ICH score demonstrated increased predictive validity with minimized confounding by care limitations, making it a useful tool for severity assessment in ICH patients.

Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves

Aims Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time‐window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH. Methods and results We pooled individual patient‐data (n = 2504) from a nationwide multicentre cohort‐study (RETRACE, conducted at 22 German centres) and eventually identified MHV‐patients (n = 137) with anticoagulation‐associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no‐TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity‐score matching and multivariable cox‐regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no‐TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no‐TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate‐ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67‐35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA‐timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33‐21.37; P < 0.01). The hazard for the composite—balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10‐5.70; P = 0.03). Conclusion Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing—between least risks for thromboembolic and haemorrhagic complications—provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk. Figure. No Caption available.