Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial.

BACKGROUND: This study was conducted to determine the effect of hypothermic temperature control after in-hospital cardiac arrest (IHCA) on mortality and functional outcome as compared with normothermia. METHODS: An investigator initiated, open-label, blinded-outcome-assessor, multicenter, randomized controlled trial comparing hypothermic temperature control (32-34°C) for 24 h with normothermia after IHCA in 11 hospitals in Germany. The primary endpoint was all-cause mortality after 180 days. Secondary end points included in-hospital mortality and favorable functional outcome using the Cerebral Performance Category scale after 180 days. A Cerebral Performance Category score of 1 or 2 was defined as a favorable functional outcome. RESULTS: A total of 1055 patients were screened for eligibility and 249 patients were randomized: 126 were assigned to hypothermic temperature control and 123 to normothermia. The mean age of the cohort was 72.6±10.4 years, 64% (152 of 236) were male, 73% (166 of 227) of cardiac arrests were witnessed, 25% (57 of 231) had an initial shockable rhythm, and time to return of spontaneous circulation was 16.4±10.5 minutes. Target temperature was reached within 4.2±2.8 hours after randomization in the hypothermic group and temperature was controlled for 48 hours at 37.0°±0.9°C in the normothermia group. Mortality by day 180 was 72.5% (87 of 120) in hypothermic temperature control arm, compared with 71.2% (84 of 118) in the normothermia group (relative risk, 1.03 [95% CI, 0.79-1.40]; P=0.822). In-hospital mortality was 62.5% (75 of 120) in the hypothermic temperature control as compared with 57.6% (68 of 118) in the normothermia group (relative risk, 1.11 [95% CI, 0.86-1.46, P=0.443). Favorable functional outcome (Cerebral Performance Category 1 or 2) by day 180 was 22.5% (27 of 120) in the hypothermic temperature control, compared with 23.7% (28 of 118) in the normothermia group (relative risk, 1.04 [95% CI, 0.78-1.44]; P=0.822). The study was prematurely terminated because of futility. CONCLUSIONS: Hypothermic temperature control as compared with normothermia did not improve survival nor functional outcome at day 180 in patients presenting with coma after IHCA. The HACA in-hospital trial (Hypothermia After Cardiac Arrest in-hospital) was underpowered and may have failed to detect clinically important differences between hypothermic temperature control and normothermia. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique Identifier: NCT00457431.

EKOS™ Jena Experience: Safety, Feasibility, and Midterm Outcomes of Percutaneous Ultrasound-Assisted Catheter-Directed Thrombolysis in Patients with Intermediate-High-Risk or High-Risk Pulmonary Embolism.

Background: Percutaneous catheter-based ultrasound-assisted thrombolysis (UACDT) is recommended for patients with intermediate-high-risk or high-risk pulmonary embolism (PE) in whom systemic thrombolysis has failed or is contraindicated. Aim: To evaluate the safety and efficiency of UACDT in patients with intermediate-high-risk or high-risk PE. Methods: Between October 2017 and January 2020, we performed UACDT using the EkoSonic™ Endovascular System (EKOS™) in 51 patients (21 males, age 63 ± 18 years) with a sPESI of 1.3 ± 0.7. The EKOS™-catheter was implanted within 24 h after admission. Over 15 hours, 11.5 mg of alteplase was administered per catheter. We evaluated right ventricular stress and cardiac biomarkers before and after UACDT. Results: 24 h post-UACDT, median RV/LV ratio decreased from 1.13 to 0.96 (p < 0.001) and the mean sPAP decreased from 47 ± 3 to 32 ± 2 mmHg + CVP (p < 0.0002). There were 6 major bleeding events resulting in transfusion. No stroke, myocardial infarction, right heart decompensation, or recurrent PE occurred. 31 patients (63%) were discharged without any signs of right ventricular stress. After at least 3 months, 73% of our patients did not show any signs of right ventricular dysfunction. The mean RV/LV ratio decreased to 0.75 ± 0.03 (p < 0.0001) in comparison with pre-UACDT, sPAP to 23 mmHg + CVP (p < 0.0001), and BNP to 40 pg/ml (p < 0.0001). Conclusions: The treatment with UACDT reduced right heart stress during the first 24 hours and midterm in patients with intermediate-high-risk or high-risk PE at an acceptable rate of severe complications.

Sex-specific differences and outcome in elderly patients after survived out-of-hospital cardiac arrest.

BACKGROUND: Little is known about sex differences in elderly patients after out-of-hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC) and subsequent target temperature management (TTM). Therefore, this study was designed to evaluate sex-specific differences in survival and neurological outcome in elderly patients at 28-day and 180-day follow-up. METHODS: A total of 468 nontraumatic OHCA survivors with preclinical ROSC and an age of ≥ 65 years were included in this study. Sex-specific differences in survival and a favorable neurological outcome according to the cerebral performance category (CPC) score were evaluated as clinical endpoints. RESULTS: Of all participants included, 70.7% were men and 29.3% women. Women were significantly older (p = 0.011) and were more likely to have a nonshockable rhythm (p = 0.001) than men. Evaluation of survival rate and favorable neurological outcome by sex category showed no significant differences at 28-day and 180-day follow-up. In multiple stepwise logistic regression analysis, age (odds ratio 0.932 [95% confidence interval 0.891-0.951], p = 0.002) and time of hypoxia (0.899 [0.850-0.951], p < 0.001) proved to be independent predictors of survival only in male patients, whereas an initial shockable rhythm (4.325 [1.309-14.291], p = 0.016) was associated with 180-day survival in female patients. The majority of patients (93.7%) remained in the same CPC category when comparing 28-day and 180-day follow-up. CONCLUSION: Our results show no significant sex-specific differences in survival or favorable neurological outcome in elderly patients after having survived OHCA, but sex-specific predictors for 180-day survival. Moreover, the neurological assessment 28 days after the index event also seems to provide a valid indication for the further prognosis in elderly patients.

Prognostication of neurologic outcome using gray-white-matter-ratio in comatose patients after cardiac arrest.

BACKGROUND: This study aimed to assess the prognostic value regarding neurologic outcome of CT neuroimaging based Gray-White-Matter-Ratio measurement in patients after resuscitation from cardiac arrest. METHODS: We retrospectively evaluated CT neuroimaging studies of 91 comatose patients resuscitated from cardiac arrest and 46 non-comatose controls. We tested the diagnostic performance of Gray-White-Matter-Ratio compared with established morphologic signs of hypoxic-ischaemic brain injury, e. g. loss of distinction between gray and white matter, and laboratory parameters, i. e. neuron-specific enolase, for the prediction of poor neurologic outcomes after resuscitated cardiac arrest. Primary endpoint was neurologic function assessed with cerebral performance category score 30 days after the index event. RESULTS: Gray-White-Matter-Ratio showed encouraging interobserver variability (ICC 0.670 [95% CI: 0.592-0.741] compared to assessment of established morphologic signs of hypoxic-ischaemic brain injury (Fleiss kappa 0.389 [95% CI: 0.320-0.457]) in CT neuroimaging studies. It correlated with cerebral performance category score with lower Gray-White-Matter-Ratios associated with unfavourable neurologic outcomes. A cut-off of 1.17 derived from the control population predicted unfavourable neurologic outcomes in adult survivors of cardiac arrest with 100% specificity, 50.3% sensitivity, 100% positive predictive value, and 39.3% negative predictive value. Gray-White-Matter-Ratio prognostic power depended on the time interval between circulatory arrest and CT imaging, with increasing sensitivity the later the image acquisition was executed. CONCLUSIONS: A reduced Gray-White-Matter-Ratio is a highly specific prognostic marker of poor neurologic outcomes early after resuscitation from cardiac arrest. Sensitivity seems to be dependent on the time interval between circulatory arrest and image acquisition, with limited value within the first 12 h.

Age-associated outcomes after survived out-of-hospital cardiac arrest and subsequent target temperature management.

BACKGROUND: The registry of the German Society of Intensive Care and Emergency Medicine was founded to analyze outcome of modern post-resuscitation care. METHODS: A total of 902 patients were analyzed in this retrospective, multicenter, and population-based observational trial on individuals suffering from out-of-hospital cardiac arrest. All patients had return of spontaneous circulation (ROSC) and received TTM after admitted to an intensive care unit. Outcome was focused on age and analyzed by creating 4 subgroups (<65, 65-74, 75-84, ≥85 years). Twenty-eight day and 180-day survival and a favorable neurological outcome according to the Cerebral Performance Category scale were evaluated as clinical endpoints. RESULTS: At 28-day and 180-day follow-up, 44.8% and 53.4% of all patients had died, respectively. The evaluation of survival rate by age category revealed a higher mortality, but not an unfavorable neurological prognosis with increasing age. In multiple stepwise regressions, age, time to ROSC, bystander resuscitation, and cardiac cause of cardiac arrest were associated with increased chance of 180-day survival and, in addition, bystander resuscitation, time of hypoxia, and a defibrillation performed by emergency medical service were associated with a favorable neurological outcome at 180-day follow-up. CONCLUSION: Increasing age was associated with a higher mortality, but not with an unfavorable neurological outcome. The majority of survivors had a favorable neurologic outcome 6 months after cardiac arrest.

Percutaneous support of the failing left and right ventricle-recommendations for the use of mechanical device therapy.

Patients in cardiogenic shock and acute heart failure show high mortality and morbidity despite aggressive and invasive methods such as percutaneous coronary intervention and the use of mechanical support devices. Percutaneous implantation of active hemodynamic support is often the only option for hemodynamic stabilization of patients in cardiogenic shock. Therefore, current guidelines support the use of these devices. Standardized protocols and clinical algorithms for the use of these support devices decrease mortality in these patients. The aim of this review is an overview of current therapies of cardiogenic shock with special focus on mechanical support devices and the suggestion of a clinical algorithm for the differential use of current devices as well as the hemodynamic monitoring of such patients in order to reduce mortality in cardiogenic shock.

Cerebral hypoxia, missing cortical somatosensory evoked potentials and recovery of consciousness.

BACKGROUND: Bilaterally absent N20 components of the sensory evoked potentials (SEP) from the median nerve are regarded as accurately predicting poor outcome after cardiac arrest. CASE PRESENTATION: We are reporting on a patient, who regained consciousness despite this ominous finding. Early after cardiac arrest, MRI showed signal alterations in diffusion weighted imaging (DWI) bilaterally in the primary visual and sensorimotor cortex and in the basal ganglia. SEP were repeatedly absent. The patient survived shut out form sensory and visual experience and locked in for voluntary movements, but kept her verbal competence in several languages. CONCLUSION: SEP inform about integrity only of a narrow cortical strip. It is unguarded, but common practice, to conclude from absent SEP, that a patient has suffered diffuse cortical damage after cardiac arrest. Cerebral MRI with DWI helps to avoid this prognostic error and furthers understanding of the sometimes very peculiar state of mind after cardiac arrest.

Investigation of the inter-observer variability effect on the prognostic value of somatosensory evoked potentials of the median nerve (SSEP) in cardiac arrest survivors using an SSEP classification.

BACKGROUND AND PURPOSE: We investigated the inter-observer variability in interpretation of median nerve SSEPs with regard to neurological prognosis in survivors of cardiac arrest (CA). METHODS: Four experienced neurologists analyzed 163 median nerve SSEPs on the basis of a pre-defined classification of SSEPs into five patterns (A-E), with consideration of cortical potentials up to a latency of 150ms. Of these, 133 recordings were from CA survivors and 30 were from healthy volunteers. The experts were blinded to whether a SSEP finding was from a CA survivor or a healthy volunteer. They were also unaware of the neurological outcome for the resuscitated patients. Three categories were defined for decision making. These were "good neurological outcome" represented by patterns A-C, "poor neurological outcome" (patterns D and E), and "not evaluable". Experts' agreement was calculated using the kappa-coefficient. RESULTS: The mean correct prediction by the experts was 81.8% (range 76.3-86.6%) in resuscitated patients with good neurological outcome. In those with poor neurological outcome, however, correct prediction was achieved in only 63% (60.5-66%). All SSEPs from healthy volunteers were classified as "good neurological outcome". The kappa-coefficient (κ) for all decision-making classifications was 0.75; for patients with poor outcome it was 0.76 and for those with good outcome 0.88. The predictive value for poor neurological outcome of the SSEP pattern D achieved a specificity of 93.5% and that of E a specificity of 98.4%. CONCLUSION: Our study demonstrates good inter-observer agreement in the interpretation of median nerve SSEPs in CA survivors on the basis of a pre-defined SSEP evaluation set. The strongest correlation with poor outcome was found for pattern E, bilateral absence of the N20 peak.

Family satisfaction in the intensive care unit: a quantitative and qualitative analysis.

PURPOSE: To assess family satisfaction in the intensive care unit (ICU) and areas for improvement using quantitative and qualitative analyses. METHODS: Prospective cohort study performed in four (mixed surgical, neurological, and cardiological) intensive care units of a university hospital in Germany, using a translated and validated version of the Family Satisfaction in the ICU (FS-ICU) questionnaire, with questions answerable on a rating scale and three open-ended questions about strengths and weaknesses. Quantitative analysis was performed to identify items with low performance and high importance. For qualitative analysis, comments were coded and analyzed to identify important themes. Patient-related data were obtained from an electronic patient data management system. RESULTS: Participants were 215 family members visiting adult intensive care patients with length of stay over 48 h. Response rate was 28 %. Respondents were highly satisfied; summary scores were 78.3 ± 14.3 [mean ± standard deviation (SD)] on a scale of 0 (poor) to 100 (excellent). Regression analysis failed to identify association with patient- or family-related factors. The following themes for possible improvement emerged from both quantitative and qualitative analyses: patient agitation-consistency, clarity and completeness of information-emotional support-respect and compassion towards families. Families were also dissatisfied with the waiting room, ICU atmosphere, and amenities for visiting relatives. CONCLUSIONS: Families report high satisfaction with intensive care. Nevertheless, there is room for improvement, in particular regarding how ICU staff communicate with families and provide emotional support.

Homozygous carrier of the NOD2 1007fs frame-shift mutation presenting with refractory community-acquired spontaneous bacterial peritonitis and developing fatal pulmonary mucormycosis: A case report.

Genetic variants of the innate immune system contribute to episodes of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis. We herein report the case of a patient with the homozygous nucleotide-binding oligomerization domain containing 2 (NOD2) frame-shift mutation 1007fs presenting with sepsis and community-acquired SBP by Escherichia coli. Secondary peritonitis, pancreatic ascites and malignant causes were excluded by extensive diagnostic work-up. First-line treatment with ceftriaxone was not successful despite in vitro sensitivity of the isolated strain. Despite prolonged second-line treatment with imipenem/cilastatin and intermittent ascites drainage, the ascitic fluid neutrophil count remained markedly elevated in this patient. In the course of the disease the patient developed pneumonia with identification of the typical hyphae of mucormycosis in the bronchoalveolar lavage and died of sepsis with multi-organ failure. On the basis of this observation, variants of the innate immunity have to be considered in therapy-refractory SBP, even when they are community-acquired and caused by cephalosporin-sensitive Enterobacteriaceae.

Survival does not improve when therapeutic hypothermia is added to post-cardiac arrest care.

BACKGROUND: We investigated whether the use of therapeutic hypothermia improves the outcome after cardiac arrest (CA) under routine clinical conditions. METHOD: In a retrospective study, data of CA survivors treated from 2003 to 2010 were analysed. Of these, 143 patients were treated with hypothermia at 33 ± 0.5°C for 24h according to predefined inclusion criteria, while 67 who did not fulfil these criteria received comparable therapy without hypothermia. RESULTS: 210 patients were included, 143 in the hypothermia group (HG) and 67 in the normothermia group (NG). There was no significant difference in mortality between the groups; 69 (48.2%) in the HG died in the first four weeks, compared to 30 patients (44.8%) in the NG (p=0.659). Patients in the NG were older and more seriously ill, and CA occurred more often in-hospital. Binary logistic regression revealed ventricular fibrillation (p=0.044), NSE serum level < 33 ng ml⁻¹ (p<0.001), age (p=0.035) and witnessed cardiac arrest (p=0.043) as independent factors significantly improving survival after CA, whereas hypothermia was not (p=0.69). The target temperature was maintained for a significantly longer time (19.5h vs. 15.2h; p=0.003) in hypothermia patients with a favourable outcome than in those with an unfavourable outcome. CONCLUSION: There was no improvement in survival rates when hypothermia was added to standard therapy in this case series, as compared to standard therapy alone. The time at target temperature may be of relevance. We need better evidence in order to expand the recommendations for hypothermia after CA.

Fondaparinux cross-reacts with heparin antibodies in vitro in a patient with fondaparinux-related thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) related to fondaparinux has been rarely reported, although the ability of fondaparinux to cross-react with heparin antibodies has been often a subject of debate. A patient previously exposed to unfractionated heparin and low-molecular-weight heparin (LMWH) was diagnosed with HIT. During treatment with fondaparinux for 5 consecutive days, his thrombocytopenia significantly deteriorated. A functional platelet activation test in vitro showed clear platelet activation after serum exposure with fondaparinux. After discontinuation of fondaparinux, the platelet count was rapidly reestablished. Fondaparinux cross-reacted with heparin antibodies in this case of HIT, resulting in a deterioration of thrombocytopenia. The implication of this drug in HIT was observed clinically and demonstrated in vitro using a platelet activation test.

An unusual case of progressive shock and highly elevated procalcitonin level.

A 21-year-old man with signs and symptoms of rapidly progressive shock was admitted to the intensive care unit for treatment of suspected sepsis. Levels of inflammatory markers (including procalcitonin) were highly elevated, but no obvious focus of infection was apparent. Initial sepsis therapy included administration of broad-spectrum antibiotics, vasoconstrictors, and drotrecogin alfa. Cultures of blood, sputum, and urine showed no growth, and no viruses were detected. The random (no stimulation with corticotropin) cortisol level at admission was less than 25 nmol/L. Assays for autoantibodies to the adrenal cortex were strongly positive and confirmed the diagnosis of adrenal failure caused by Addison disease. After initiation of steroid therapy, the patient fully recovered. Although increased procalcitonin levels are considered a reliable and specific indicator of severe generalized infections and bacterial sepsis, elevated procalcitonin levels cannot be relied on when trying to differentiate between addisonian crisis and septic shock.

[Eosinophilia--a challenging differential diagnosis]. / Eosinophilie--eine differentialdiagnostische Herausforderung.

BACKGROUND: Eosinophilia is not uncommon in clinical practice. The main causes are allergies and parasitic infections. Rarely, eosinophilia is associated with pulmonary affections, malignant tumors, gastroenteritis, and autoimmune diseases. A new classification based on pathophysiological data for the hypereosinophilic syndrome in order to simplify diagnosis and therapy was introduced in 2006. CASE REPORT: A 22-year-old man was admitted to another hospital because of acute abdominal pain. An unspecific colitis was diagnosed. Blood counts showed a mild neutrophilic leukocytosis (12.6 Gpt/l) with a severe relative eosinophilia (30%), thrombocytopenia (67 Gpt/l), and an increased C-reactive protein (CRP 122 mg/l). The patient also had a deep venous thrombosis of the left leg. An explorative laparotomy was performed because of a strong suspicion of a presacral abscess. Pulmonary embolism and embolic pneumonia developed after surgery. A macular-cockade exanthema on the trunk and extremities was found. Histological examination revealed perivascular eosinophilic infiltrates. Histological and cytological analysis of bone marrow showed many eosinophilic granulocytes and a hypercellular medulla without increased numbers of blasts. No parasites in the blood and stools were found, and there was no evidence of neoplasm or cardiac involvement. p- and c-ANCAs (antineutrophil cytoplasmic antibodies), ANAs (antinuclear antibodies), and antibody against dsDNA were negative. Further genetic, FISH (fluorescence in situ hybridization), and PCR (polymerase chain reaction) analyses showed no evidence for chromosomal aberrations. An undefined hypereosinophilic syndrome with multiple organ involvement was diagnosed. Shortly after starting an oral prednisolone therapy (1 mg/kg body weight), the eosinophilia normalized. This therapy was stopped after 2 months and the patient is now, 6 months after diagnosis, in normal health. CONCLUSION: As demonstrated in this case, eosinophilia requires a broad differential diagnosis. A hypereosinophilic syndrome can involve many organs and mimic other diseases. The new classification of the hypereosinophilic syndrome from 2006, based on pathophysiological insights, may foster better diagnosis and therapy for this rare disease.

Serum concentration of NSE and S-100b during LVAD in non-resuscitated patients.

BACKGROUND AND OBJECTIVES: Increased serum concentrations of brain-derived proteins neuron-specific enolase (NSE) and protein S-100beta (S-100b) are used as early predictors of long-term outcome in unconscious survivors after cardiopulmonary resuscitation (CPR). We investigated whether use of short-term Left Ventricular Assist Devices (LVAD) in patients undergoing percutaneous coronary intervention (PCI) effect serum concentrations of NSE and S-100b, because use of such devices in resuscitated cardiogenic shock patients increased during the last years. METHOD: We analysed data from 80 consecutive non-resuscitated patients who received LVAD support. 43 patients with uncomplicated myocardial infarction (AMI) without LVAD support after PCI formed the reference group. RESULTS: 69 patients (86%) with LVAD support survived and were discharged from hospital. We observed an increase in NSE serum levels in 93.6% and in S-100b serum levels in 58.6% of these patients during LVAD support. This increase was significant in comparison to the upper limit of normal (ULN) of both biomarkers and to the reference group. Cardiogenic shock patients showed significantly higher serum concentrations of both neuroproteins than patients after high-risk PCI, and after AMI during LVAD support. The use of axial flow pumps led to significantly higher serum concentrations of NSE compared to patients on IABP, but not of S-100b. Thrombocytes and haemoglobin (Hb) concentrations declined significantly during LVAD support. Surprisingly, we also observed a significant increase in NSE in the reference group. CONCLUSIONS: LVAD support after PCI is associated with a significant increase in NSE serum concentration as well as in S-100b. We therefore postulate an overestimation of the extent of hypoxic brain damage in unconscious survivors after CPR if treatment include LVAD support or PCI or both procedures. The increase in NSE can be partly explained by alteration of thrombocytes and other blood cells. However, the increase in S-100b remains unexplained since S-100b does not occur in peripheral blood cells. An additional release of both biomarkers from ischemic myocardium or cerebral microembolism should be drawn into consideration.

Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow Coma Scale.

BACKGROUND AND PURPOSE: Patients resuscitated from cardiac arrest are at risk of subsequent death or poor neurological outcome up to a persistent vegetative state. We investigated the prognostic value of several epidemiological and clinical markers and two neuroproteins, neuron-specific enolase (NSE) and S-100 protein (S-100), in 97 patients undergoing cardiopulmonary resuscitation (CPR) after non-traumatic cardiac arrest between 1998 and 2002. RESULTS: 52.6% of the patients died, 28.8% survived with severe, moderate or without neurological disorders, and 18.6% remained in a persistent vegetative state. Unconsciousness>48 h after CPR predicted a 60.6-fold (95% CI 14.3287-257.205, p=0.001) and a Glasgow Coma Scale (GCS)<6 points after 72 h a 11.2-fold (CI 95%, 3.55-36.44, p<0.001) risk of poor neurological outcome. Serum levels>or=65 ng/ml for NSE and >or=1.5 microg/l for S-100 increased the risk of death and persistent vegetative state 16.8 (95% CI 2.146-131.520)- and 12.6 (95% CI 1.1093-99.210)-fold, respectively. By combination of the GCS with elevated serum concentrations of both neuroproteins above the cut off levels on third day after CPR a poor neurological outcome was predicted with a specificity of 100%. CONCLUSION: The combination of GCS with the serum levels of both neuroproteins at 72 h after CPR permit a more reliable prediction of outcome in post arrest coma than the single markers alone, independent of the application of anaesthetic agents.