Effects of therapeutic hypothermia and kinetics of serum protein S100B after cardiopulmonary resuscitation

Introduction. Post-resuscitation care is regulated by international guidelines. A milestone of these is the application of therapeutic hypothermia (TH). The aims of our study were: to determine the 30-day-mortality for our patients, to monitor the efficacy and effects of TH, and to investigate serum protein S100B – as an early prognostic marker. Materials and Methods. In our study, 57 patients, treated after cardiopulmonary resuscitation (CPR) on a multidisciplinary intensive care unit, were included. Patients were divided into groups who received and who didn’t receive TH. 30-day-mortality was determined as an end-point. Effects of TH were monitored using statistical analysis according to clinical parameters and laboratory tests. Serum protein S100B levels were measured with ELISA technique on 20 randomised patients at admission and the 1st, 3rd and 5th day after CPR. Results. Total 30-day-mortality was 74%. TH did not reduced the 30-day-mortality (73% vs. 74%, p>0.05). We found a significant correlation between TH and serum lactate concentration after admission (0h, p=0.006) and at 12 (p=0.045) and 36 (p=0.049) hours after CPR. On the 3rd (p=0.005) and 4th (p=0.043) day after CPR, as a result of TH, platelet count was significantly higher compared to normothermic samples. There was no significant difference in protein S100B levels between the normothermic and TH group and protein S100B levels did not correlate with 30-day-mortality. Conclusion. Despite recommendations of international guidelines, we cannot prove the beneficial effect of TH, or a correlation of protein S100B levels with a positive outcome

Examination of the Cerebral Ischaemia-induced Inflammatory Response after Carotid Artery Stenosis and Cardiopulmonary Resuscitation

According to recent statistical analysis, leading causes of mortality in Europe are cardiovascular diseases. 45% of the total mortality has cardiovascular origin. Ischaemic heart disease is the most common form of cardiovascular diseases. Among patients with ischaemic heart disease one of the main cause of mortality is sudden cardiac arrest. The range of incidence of out-of-hospital cardiac arrest is 38-55/100,000/year. Stroke is the second most common cardiovascular disorder in Europe and in other developed regions. A significant proportion of these cases are developed from thromboembolic complications of atherosclerotic lesions of the carotid arteries. The complex diagnostic and therapeutic considerations of extracranial carotid artery stenosis, such as cardiopulmonary resuscitation (CPR) and post-resuscitation care are controlled by international guidelines. Milestones of post-resuscitation care are the optimal target temperature management for favourable mortality and neurogical outcomes and the optimal and reliable prognostication after CPR. One pillar of this later could be the appropriate use of biomarkers. Matrix metalloproteinases (MMPs) are zinc and calcium dependent endoproteinases with specified structure. In the human tissues 23 different MMP were identified. Main role of these are the breakdown of protein structure of the extracellular matrix. Beside this, MMPs play significant roles in complex physiological and pathological processes such as morphogenesis, angiogenesis, and inflammatory response. Four different tissue inhibitors of matrix metalloproteinases (TIMPs) perform the inhibition of MMP activity in human tissues. TIMPs have identified roles in the activation of pro-MMPs and in the regulation of cellular differentiation, morphological development and apoptosis. Near intact cerebral endothelial function, the production of MMPs and other proteinases are minimal. During cerebral ischemic-reperfusion damage the expression of MMPs (mainly MPP-9 and MMP-2) increases significantly. As a result of this process, endothelial and blood-brain-barrier dysfunction and cerebral oedema can be developed. In this doctoral thesis, we aimed to investigate the time courses of MMP-TIMP system during partial and global cerebral ischaemic-reperfusion in connection with elective carotid artery stenting and cardiopulmonary resuscitation. Other aims were the research of the mortality rate, the effects of therapeutic hypothermia and function of protein S100B as a prognostic marker after CPR

Comparison of the perioperative time courses of matrix metalloproteinase-9 (MMP-9) and its inhibitor (TIMP-1) during carotid artery stenting (CAS) and carotid endarterectomy (CEA)

Abstract Background Our aim was to compare the perioperative time courses of matrix metalloproteinase-9 (MMP-9) and its inhibitor (TIMP-1) in during carotid endarterectomy (CEA) and carotid artery stenting (CAS). Methods In our prospective study, twenty-five patients who were scheduled to undergo CAS were enrolled. We used a matched, historical CEA group as controls. Blood samples were collected at four time points: T1: preoperative; T2: 60 min after stent insertion; T3: first postoperative morning; and T4: third postoperative morning. Plasma MMP-9 and TIMP-1 levels were measured by ELISA. Results In the CEA group, the plasma levels of MMP-9 were significantly elevated at T3 compared to T1. In the CAS group, there was no significant difference in MMP-9 levels in the perioperative period. MMP-9 levels were significantly higher in the T3 samples of the CEA group compared to the CAS group. Significantly lower TIMP-1 levels were measured in both groups at T2 than at T1 in both groups. MMP-9/TIMP-1 at T3 was significantly higher than that at T1 in the CEA group compared to both T1 and the CAS group. Conclusions CAS triggers smaller changes in the MMP-9-TIMP-1 system during the perioperative period, which may correlate with a lower incidence of central nervous system complications. Additional studies as well as cognitive and functional surveys are warranted to determine the clinical relevance of our findings. Trial registration NIH U.S. National Library of Medicine, Clinicaltrials.gov,NCT03410576, 24.01.2018, Retrospectively registere

Perioperative time course of matrix metalloproteinase-9 (MMP-9), its tissue inhibitor TIMP-1 & S100B protein in carotid surgery

Background & objectives: Ischaemic stroke is a life burdening disease for which carotid endarterectomy (CEA) is considered a gold standard intervention. Pro-inflammatory markers like matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) and S-100 Beta (S100B) may have a role in the early inflammation and cognitive decline following CEA. This study was aimed to describe the perioperative time courses and correlations between of MMP-9, TIMP-1 and S100B following CEA. Methods: Fifty four patients scheduled for CEA were enrolled. Blood samples were collected at four time points, T 1 : preoperative, T 2 : 60 min after cross-clamp release, T 3 : first postoperative morning, T 4 : third postoperative morning. Twenty atherosclerotic patients were included as controls. Plasma MMP-9, TIMP-1 and S100B levels were estimated by ELISA. Results: TIMP-1 was decreased significantly in the CEA group (P<0.01). Plasma MMP-9 was elevated and remained elevated from T 1-4 in the CEA group (P<0.05) with a marked elevation in T 3 compared to T 1 (P<0.05). MMP-9/TIMP-1 was elevated in the CEA group and increased further by T 2 and T 3 (P<0.05). S100B was elevated on T 2 and decreased on T 3-4 compared to T 1 . Interpretation & conclusions: Our study provides information on the dynamic changes of MMP-9-TIMP-1 system and S100B in the perioperative period. Preoperative reduction of TIMP-1 might be predictive for shunt requirement but future studies are required for verification

Comparison of VividTrac®, Airtraq®, King Vision®, Macintosh Laryngoscope and a Custom-Made Videolaryngoscope for difficult and normal airways in mannequins by novices

Abstract Background Direct laryngoscopy remains the gold standard for endotracheal intubation and is preferred by experienced operators. However, an increasing number of reports currently support videolaryngoscopy, particularly for novice users. The widespread use of videolaryngoscopy may be limited due to financial limitations, especially in low-income countries. Therefore, affordable single-use scopes are now becoming increasingly popular. We sought to compare these new scopes with direct laryngoscopes and the previously tested videolaryngoscopes in mannequins by novices. Methods Fifty medical students were recruited to serve as novice users. Following brief, standardized training, students were asked to execute endotracheal intubation with each of the devices, including the Airtraq®, a custom-made videolaryngoscope, the King Vision®, the Macintosh laryngoscope and the VividTrac®, on an airway trainer (Laerdal Airway Management Trainer®) in normal and difficult airway scenarios. We evaluated the time to and the proportion of successful intubation, the best view of the glottis, esophageal intubation, dental trauma and user satisfaction. Results We observed no differences in esophageal intubation. However, intubation-related times, the view of the glottis and operator satisfaction were significantly better throughout the study with the commercial videolaryngoscopes. In comparison, the custom-made videolaryngoscope performance proved to be similar to that of the Macintosh laryngoscope. The VividTrac® performance was similar (P > 0.05) or significantly better than that of the King Vision® in both scenarios. Conclusions Based upon our results, the Airtraq®, King Vision® and VividTrac® were superior to the Macintosh laryngscope in both normal and difficult airway scencarios for novice users. In particular, our study is the first to report that the VividTrac® shows promise for further clinical evaluation