Long-term neurological outcomes in patients aged over 90 years who are admitted to the intensive care unit following cardiac arrest.

BACKGROUND: The number of cardiac arrests (CA) in the group of very elderly patients (≥ 90 years) is expected to increase markedly due to the world`s rapidly ageing population. However, only little is known about long term outcome, CA- and intensive care unit (ICU) characteristics of patient's ≥ 90 years (nonagenarians) suffering from CA. METHODS: This single-center retrospective study included all adult patients ≥ 90 years after CA and return of spontaneous circulation (ROSC) which were treated at our ICU between January 1st 2008 and September 15th 2016. Patients were followed at least 1-Year after ICU discharge for assessment of survival and neurological outcome. Aim of the study was to evaluate CA- and patients characteristics, as well as ICU- and neurological outcome after CA in patient's ≥ 90 years. RESULTS: 657 patients ≥ 90 years were treated at our ICU during the study period, of these we could identify 48 patients with CA and successful resuscitation. 27 (56%) were female and the median age was 91.7 (90.7 - 92.6) years. 41 (85%) patient suffered from in-hospital CA. Cardiac events leading to CA were observed in 19 (40%) patients. Initial rhythm was shockable (VT/VF) in 12 (25%) patients and time to ROSC was median 4 (1.6 - 9.5) minutes. Patients after CA who survived the ICU stay had significantly lower SAPS II score (44 (36 - 55) vs. 58 (46.5 - 75.5), p < 0.05), lower maximum lactate (2.8 (1.9 - 4.3) mmol/l vs. 6.2 (4 - 9) mmol/l, p < 0.001) and higher pH (7.29 (7.26 - 7.38) vs. 7.23 (7.12 - 7.32), p < 0.05) on admission compared to patients with CA who did not survive the ICU stay. Overall, after CA, 39 (81%) patients needed mechanical ventilation, 44 (92%) received catecholamine support, 17 (35%) received red blood cell transfusion and 4 (8%) received renal replacement therapy. Mechanical ventilation and red blood cell transfusion was significantly more common in ICU non-survivors (both p < 0.05). 19 (46%) patients survived the ICU-stay, of these 86% had favourable neurological outcome (CPC I/II) at ICU discharge. One year survival rate was 23% (n = 11), of these 55% (n = 6) had favorable neurological outcome. CONCLUSIONS: 46% of successfully resuscitated nonagenarians survived the ICU stay, the majority with favourable neurological outcome at ICU discharge. Resuscitation and post-CA care, in the highly selected group of very elderly patients (≥ 90 years), seems to be justified.

Ozone Generation during High-Voltage Leak Detection: Fiction or Reality?

In order to further clarify if and how much ozone is generated during high-voltage leak detection and to identify measures to reduce the impact of ozone generation on product quality, a highly sensitive analytical system was employed to investigate the generation of ozone at different operational conditions of high-voltage leak detection integrity testing. The analytical system is based on oxidation of Iodide ions in solution and identification of the Iodine formed by N, N-Diethyl-p-phenylendiamine (DPD) according to DIN 38403. Sensitivity of the system was found suitable to detect ozone levels as low as 0.025 ppm (mg/L). High-voltage leak detection process parameters-inspection speed, high voltage, filling level of the ampoule, and exposure time to the ampoule to high voltage-were varied between maximum and minimum values applicable in integrity testing of different ampoule sizes. For variation of exposure time, ampoules were repetitively tested by the leak testing machine to achieve a maximum exposure time of the ampoule up to 24 s (exposure time during production ≤2.4 s). No ozone was detected during the study under all inspection conditions. Even repeated exposure of the ampoules to high-voltage leak detection did not result in generation of measurable ozone levels. It has to be concluded that high voltage leak detection is not prone to causing oxidation of the drug products.LAY ABSTRACT: For drug products in ampoules, 100% integrity testing is requested both by European and US regulations. Detection of integrity defects like small holes or cracks in the ampoule can be performed by numerous methods. Due to automation requirements, only three methods have been used during routine production-vacuum decay, head space infrared spectroscopy, and high-voltage leak detection. High-voltage leak detection is the most common method used in the pharmaceutical industry for 100% integrity testing of ampoules, but resent publications showed considerable oxidation of an air-sensitive active pharmaceutical ingredient during the integrity testing process. It was assumed that ozone generated in the inside of the vial due to exposure of the product to the high voltage during the testing process may be responsible for this result. As ozone is a very aggressive and non-selective oxidant, this result posed a serious thread not only to this product but also to the quality of many other products subjected to integrity testing by high-voltage leak detection.

Clinical characteristics and outcome of very elderly patients ≥90 years in intensive care: a retrospective observational study.

BACKGROUND: Since the overall prognosis of very elderly patients is generally limited, admissions to intensive care in these patients are often restricted. Therefore, only very few information is available on the prognosis of nonagenarians after intensive care treatment. The aim of this study was to analyze the clinical characteristics and outcomes of very elderly patients (≥90 years) admitted to an intensive care unit (ICU). METHODS: Monocentric, retrospective observational study of all patients aged ≥90 years admitted to the Department of Intensive Care Medicine with a total capacity of 132 ICU beds at the University Medical Center Hamburg in Germany between January 2008 and June 2013. A multivariate Cox regression analysis was used to identify risk factors for 28-day outcome. RESULTS: A total of 372 patients ≥90 years of age were admitted to one of the departments ICUs. The majority of patients (66.7 %) were admitted as an emergency admission, of which half underwent unscheduled surgery. 39.8 % of patients required support by mechanical ventilation and vasoactive drugs, and 1.9 % of patients received renal replacement. ICU and hospital mortality rates were 18.3 and 30.9 %, respectively. Overall survival at 1 year after hospital discharge was 34.9 %. Multivariate Cox regression analysis revealed creatinine, bilirubin, age, and necessity of catecholamines as independent risk factors and scheduled surgery as protective factor for 28-day outcome. CONCLUSION: Nearly 70 % of patients aged ≥90 years were discharged alive from hospital following treatment at the ICU, and more than half of them were still alive 1 year after their discharge. The results suggest that 1-year survival prognosis of very old ICU patients is not as poor as often perceived and that age per se should not be an exclusion criterion for ICU admission. TRIAL REGISTRATION: WF-0561/13.

Direct angiotensin II type 2 receptor stimulation in Nω-nitro-L-arginine-methyl ester-induced hypertension: the effect on pulse wave velocity and aortic remodeling.

Pulse wave velocity (PWV), a direct marker of arterial stiffness, is an independent cardiovascular risk factor. Although the angiotensin II type 1 receptor blockade belongs to major antihypertensive and cardioprotective therapies, less is known about the effects of long-term stimulation of the angiotensin II type 2 receptor. Previously, compound 21, a selective nonpeptide angiotensin II type 2 receptor agonist improved the outcome of myocardial infarction in rats along with anti-inflammatory properties. We investigated whether compound 21 alone or in combination with angiotensin II type 1 receptor blockade by olmesartan medoxomil could prevent PWV increase and aortic remodeling in N(ω)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension. Male adult Wistar rats (n=65) were randomly assigned to control, L-NAME, L-NAME+compound-21, L-NAME+olmesartan, and L-NAME+olmesartan+compound-21 groups and treated for 6 weeks. We observed that L-NAME hypertension was accompanied by enhanced PWV, increased wall thickness, and stiffness of the aorta, along with elevated hydroxyproline concentration. Olmesartan completely prevented hypertension, PWV and wall thickness increase, and the increase of aortic stiffness and partly prevented hydroxyproline accumulation. Compound 21 partly prevented all of these alterations, yet without concomitant prevention of blood pressure rise. Although the combination therapy with olmesartan and compound 21 led to blood pressure levels, PWV, and wall thickness comparable to olmesartan-alone-treated rats, only in the combination group was complete prevention of increased hydroxyproline deposition achieved, resulting in even more pronounced stiffness reduction. We conclude that chronic angiotensin II type 2 receptor stimulation prevented aortic stiffening and collagen accumulation without preventing hypertension in rats with inhibited NO synthase. These effects were additive to angiotensin II type 1 receptor blockade, yet without additional blood pressure-lowering effect, and they seem to be NO and blood pressure independent.