Efficacy of Glucocorticoid Administration in Patients with Cardiac Arrest: A Systematic Review of Clinical Studies.

BACKGROUND: The pathophysiology of cardiac arrest (CA) involves over-activation of systemic inflammatory responses, relative adrenal insufficiency, and glycocalyx damage. Corticosteroids have beneficial effects in preventing the perturbation of the endothelial glycocalyx. OBJECTIVES: The aim of this systematic review was to determine the efficacy of glucocorticoids in patients with cardiac arrest. METHODS: We searched PubMed, Scopus, ISI Web of Science, Google Scholar, and Cochrane central register for relevant clinical trials and cohort studies until September 2019. RESULTS: We retrieved 7 peer-reviewed published studies for the systematic review. Two studies were clinical trials evaluating 147 patients, while five illustrated cohort design, evaluating 196,192 patients. In total, 196,339 patients were assessed. There was limited evidence and conflicting results to establish a correlation between glucocorticoids and the survival of patients suffering from cardiac arrest. However, the links between these medications and survival-to-admission, survival-to discharge, and 1-year survival rates were strong and consistent in observational studies. CONCLUSION: The clinical evidence regarding the efficacy and safety of glucocorticoids in CA is limited to observational studies with inconsistent methodology and few clinical trials with a small sample size. Nevertheless, it seems that glucocorticoid supplementation during and after cardiopulmonary resuscitation (CPR) may have beneficial effects in terms of survival-to-admission, survival to discharge, 1-year survival rates, and an improved return of spontaneous circulation (ROSC) rate, especially in patients with hemodynamic instability and cardiovascular diseases (i.e., refractory hemodynamic shock). Future studies with high-quality, large-scale, long-term intervention and precise baseline characteristics are needed to evaluate the exact effective dose, duration, and efficacy of glucocorticoids in CA.

Rationale of Blood Purification in the Post-Resuscitation Syndrome following Out-of-Hospital Cardiac Arrest: A Narrative Review.

Even today, little is known about the pathophysiology of the post-resuscitation syndrome. Our narrative review is one of the first summarizing all the knowledge about this phenomenon. We have focused our review upon the potential role of blood purification in attenuating the consequences of the post-resuscitation syndrome. Blood purification can decrease the cytokine storm particularly when using a CytoSorb absorber. Acrylonitrile 69-based oXiris membranes can remove endotoxin and high-mobility group box 1 protein. Blood purification techniques can quickly induce hypothermia. Blood purification can be used with veno-arterial extracorporeal membrane oxygenation to remove excess water. Further trials are needed to provide more concrete data about the use of blood purification in the post-resuscitation syndrome.

Arterial blood pressure during targeted temperature management after out-of-hospital cardiac arrest and association with brain injury and long-term cognitive function.

OBJECTIVES: During targeted temperature management after out-of-hospital cardiac arrest infusion of vasoactive drugs is often needed to ensure cerebral perfusion pressure. This study investigated mean arterial pressure after out-of-hospital cardiac arrest and the association with brain injury and long-term cognitive function. METHODS: Post-hoc analysis of patients surviving at least 48 hours in the biobank substudy of the targeted temperature management trial with available blood pressure data. Patients were stratified in three groups according to mean arterial pressure during targeted temperature management (4-28 hours after admission; <70 mmHg, 70-80 mmHg, >80 mmHg). A biomarker of brain injury, neuron-specific enolase, was measured and impaired cognitive function was defined as a mini-mental state examination score below 27 in 6-month survivors. RESULTS: Of the 657 patients included in the present analysis, 154 (23%) had mean arterial pressure less than 70 mmHg, 288 (44%) had mean arterial pressure between 70 and 80 mmHg and 215 (33%) had mean arterial pressure greater than 80 mmHg. There were no statistically significant differences in survival (P=0.35) or neuron-specific enolase levels (P=0.12) between the groups. The level of target temperature did not statistically significantly interact with mean arterial pressure regarding neuron-specific enolase (Pinteraction_MAP*TTM=0.58). In the subgroup of survivors with impaired cognitive function (n=132) (35%) mean arterial pressure during targeted temperature management was significantly higher (Pgroup=0.03). CONCLUSIONS: In a large cohort of comatose out-of-hospital cardiac arrest patients, low mean arterial pressure during targeted temperature management was not associated with higher neuron-specific enolase regardless of the level of target temperature (33°C or 36°C for 24 hours). In survivors with impaired cognitive function, mean arterial pressure during targeted temperature management was significantly higher.

Mean arterial pressure during targeted temperature management and renal function after out-of-hospital cardiac arrest.

PURPOSE: This study investigates the association between mean arterial pressure (MAP) and renal function after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: Post-hoc analysis of 851 comatose OHCA-patients surviving >48 h included in the targeted temperature management (TTM)-trial. RESULTS: Patients were stratified by mean MAP during TTM in the following groups; <70 mmHg (22%), 70-80 mmHg (43%), and > 80 mmHg (35%). Median (interquartile range) eGFR (ml/min/1.73 m2) 48 h after OHCA was inversely associated with MAP-group (70 (47-102), 84 (56-113), 94 (61-124), p < .001, for the <70-group, 70-80-group and > 80-group respectively). After adjusting for potential confounders, in a mixed model including eGFR after 1, 2 and 3 days this association remained significant (pgroup_adjusted = 0.0002). Higher mean MAP was independently associated with lower odds of renal replacement therapy (odds ratioadjusted = 0.77 [95% confidence interval, 0.65-0.91] per 5 mmHg increase; p = .002]). CONCLUSIONS: Low mean MAP during TTM was independently associated with decreased renal function and need of renal replacement therapy in a large cohort of comatose OHCA-patients. Increasing MAP above the recommended 65 mmHg could potentially be renal-protective. This hypothesis should be investigated in prospective trials.

Severe metabolic acidosis after out-of-hospital cardiac arrest: risk factors and association with outcome.

BACKGROUND: Metabolic acidosis is frequently observed as a consequence of global ischemia-reperfusion after out-of-hospital cardiac arrest (OHCA). We aimed to identify risk factors and assess the impact of metabolic acidosis on outcome after OHCA. METHODS: We included all consecutive OHCA patients admitted between 2007 and 2012. Using admission data, metabolic acidosis was defined by a positive base deficit and was categorized by quartiles. Main outcome was survival at ICU discharge. Factors associated with acidosis severity and with main outcome were evaluated by linear and logistic regressions, respectively. RESULTS: A total of 826 patients (68.3% male, median age 61 years) were included in the analysis. Median base deficit was 8.8 [5.3, 13.2] mEq/l. Male gender (p = 0.002), resuscitation duration (p < 0.001), initial shockable rhythm (p < 0.001) and post-resuscitation shock (p < 0.001) were associated with an increased level of acidosis. ICU mortality rate increased across base deficit quartiles (39.1, 59.2, 76.3 and 88.3%, p for trend < 0.001), and base deficit was independently associated with ICU mortality (p < 0.001). The proportion of CPC 1 patients among ICU survivors was similar across base deficit quartiles (72.8, 67.1, 70.5 and 62.5%, p = 0.21), and 7.3% of patients with a base deficit higher than 13.2 mEq/l survived to ICU discharge with complete neurological recovery. CONCLUSION: Severe metabolic acidosis is frequent in OHCA patients and is associated with poorer outcome, in particular due to refractory shock. However, we observed that about 7% of patients with a very severe metabolic acidosis survived to ICU discharge with complete neurological recovery.

Protectiveeffects of endovascular cooling treatment on post-resuscitation syndrome and its mechanism / 中华危重病急救医学

Objective To investigate the protective function of endovascular cooling method on post-resuscitation syndrome (PRS) in porcine cardiac arrest (CA) model and its mechanism.Methods Ventricular fibrillation (VF) was electrically induced and untreated for 8 minutes in 15 healthy male porcines, cardiopulmonary resuscitation (CPR) was then initiated. All successful recovery animals were randomly divided into two groups by random number table. In normal temperature group, the core temperature was maintained at (38.0±0.5) ℃ for 12 hours. In mild hypothermia group, the mild hypothermia treatment was initiated at 5 minutes after successful resuscitation, the treatment of rapid endovascular cooling was performed to reach the target cooling temperature of (33.0±1.0) ℃, and then maintained until 6 hours after resuscitation. Rewarming was implemented at the rate of 0.7 ℃/h until the body temperature reached (38.0±0.5) ℃. Hemodynamic parameters including heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO) were continually monitored. Right femoral vein blood was collected before VF and 1, 2, 4, 6, 12 and 24 hours after resuscitation, respectively, and the serum concentrations of E-selectin, soluble thrombomodulin (sTM), and interleukin-1β(IL-1β) were determined with enzyme linked immunosorbent assay (ELISA). The survival of porcines at 24 hours after resuscitation was observed, and the neurological deficit score (NDS) was calculated for the surviving porcines. All animals were sacrificed, and brain, heart and lung tissues were collected, after hematoxylin and eosin (HE) staining, the histopathology changes were evaluated under a light microscopy.Results After 8-minute VF, 14 porcines were resuscitated successfully, 7 porcines in normal temperature group and 7 in mild hypothermia group respectively, with the resuscitation success rate of 93.3％. There was no significant difference in body weigh, core temperature, hemodynamics, or blood lactate as well as duration of CPR and the number of defibrillations between the two groups. The core temperature of normal temperature group was maintained at (38.0±0.5) ℃, while in mild hypothermia group, the hypothermia was reduced to the hypothermia range (33.0±1.0) ℃until 6 hours, then rewarmed to normothermia gradually [(38.0±0.5) ℃]. Compared with those before VF, HR was significantly increased after resuscitation in both groups, and MAP and CO were decreased, then they tended to normal. There was no significant difference in hemodynamic parameter at all time points between the two groups. Compared with those before VF, the levels of E-selectin and sTM in serum of the two groups were increased significantly at 1 hour after resuscitation, and they were decreased gradually after reaching the peak at 6 hours, and IL-1β was increased continuously with time. There was no significant difference in E-selectin (μg/L:1.34±0.52 vs. 1.60±0.61), sTM (μg/L: 19.13±0.34 vs. 19.24±0.73), or IL-1β (ng/L: 25.73±0.87 vs. 25.32±0.25) before VF between normal temperature group and mild hypothermia group (allP> 0.05). The levels of E-selection, sTM and IL-1β in mild hypothermia group were significantly lower than those in normal temperature group from 2 hours after resuscitation [E-selection (μg/L): 11.15±2.73 vs. 16.04±3.23, sTM (μg/L): 49.67±3.32 vs. 62.22±1.85, IL-1β (ng/L): 140.51±6.66 vs. 176.29±18.51, allP< 0.05], and E-selection decreased to the baseline level at 12 hours (μg/L: 1.17±0.65 vs. 1.60±0.61,P > 0.05). The 24-hour survival rates of two groups were both 100％. The NDS score of mild hypothermia group was obviously lower than that of normal temperature group (150.0±6.6 vs. 326.4±12.3,P < 0.05). In normal temperature group, neuronal cell necrosis was observed in the cerebral cortex at 24 hours after resuscitation, and nucleus was deeply stained. The myocardial necrosis and alveolar collapse was found. Meanwhile the infiltration of inflammatory cell could be found in the myocardium and alveolar. The brain, lung and myocardium injury were significantly milder in mild hypothermia group as compared with those in normal temperature group.Conclusions The intravascular cooling therapy was a safe and effective method for inducing mild hypothermia after resuscitation. This cooling effect was fast and reliable, and the rewarming speed was controllable and stable. The protective mechanism of mild hypothermia on PRS may be related to inhibiting systemic inflammatory response and reducing vascular endothelial cell injury.

An experimental study on brain protective effect of Sini decoction on post-resuscitation syndrome / 中国中西医结合急救杂志

Objective To approach the brain protective effect and mechanism of Sini decoction on rats with cardiopulmonary resuscitation (CPR) syndrome.Methods Fifty Sprague-Dawley (SD) rats were divided into sham operation group (n = 10), CPR model group (n = 20) and Sini decoction treatment group (n = 20) by random number table. The rat models were established by trachea clipping to induce cardiac arrest, and after heart beat stopped for 5 minutes, CPR was carried out. In the Sini decoction group, Sini decoction 5 g/kg was given through a stomach tube, once per 24 hours, while in the sham and CPR model groups, the same amount of normal saline was given by the same method at the same time. Venous blood was collected before CPR and 6, 12, 24, 48 and 72 hours after CPR, and the levels of serum interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent test (ELISA); after CPR for 72 hours, the rat brain tissue was obtained from all the groups, the content of caspase-3 in brain tissue was detected by immunohistochemistry method, and its protein expression caspase-3 was detected by Western Blot; the apoptosis situation of brain tissue was detected by terminal deoxynucleotidyl transferase-mediated duTP nick end labeling (TUNEL).Results With the prolongation of time, the levels of IL-6 and TNF-α in CPR model and Sini decoction groups showed a tendency firstly increased and then decreased, IL-6 reached its peak value after resuscitation for 24 hours, while TNF-α reached its peak value after resuscitation for 48 hours, and both IL-6 and TNF-α were decreased after resuscitation for 72 hours ; beginning from 6 hours after resuscitation, the levels of serum IL-6 (ng/L: 61.79±1.31, 62.49±1.42 vs. 21.48±0.79) and TNF-α (ng/L: 48.32±1.98, 25.32±1.96 vs. 18.34±2.45) in CPR model and Sini decoction treatment groups were all significantly higher than those in sham group, since 12 hours after resuscitation, the level of IL-6 was significantly lower in Sini decoction than that in CPR model group (ng/L: 70.41±2.21 vs. 88.32±1.59), and since 6 hours after resuscitation, TNF-α was obviously lower in Sini decoction group than that in CPR model group (ng/L: 25.32±1.96 vs. 48.32±1.98, allP < 0.05), both IL-6, TNF-α persisting to 72 hours after resuscitation, and their levels did not return to normal at the end of experiment in the two groups. After the end of resuscitation, the content and protein expression of caspase-3 and rate of cell apoptosis in the brain tissue in CPR model group were significantly higher than those in the sham group [caspase-3 content (A value,×103): 2.59±0.26 vs. 1.57±0.06, caspase-3 protein (gray value): 0.80±0.08 vs. 0.43±0.04, apoptosis rate: (2.01±0.08)% vs. (0.26±0.02)%, allP < 0.05], above indexes in the Sini decoction treatment group were significantly lower than those in the CPR model group [caspase-3 content (A value,×103): 1.89±0.08 vs. 2.59±0.26, caspase-3 protein (gray value): 0.57±0.02 vs. 0.80±0.08, apoptosis rate: (1.03±0.05)% vs. (2.01±0.08)%, allP < 0.05).Conclusion The Sini decoction has a protective effect on rats with post-resuscitation syndrome, and its mechanism is possibly realized by the inhibition of inflammatory factors and reduction of cell apoptosis.

Outcomes of Comatose Cardiac Arrest Survivors With and Without ST-Segment Elevation Myocardial Infarction: Importance of Coronary Angiography.

OBJECTIVES: The aim of this study was to compare outcomes and coronary angiographic findings in post-cardiac arrest patients with and without ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The 2013 STEMI guidelines recommend performing immediate angiography in resuscitated patients whose initial electrocardiogram shows STEMI. The optimal approach for those without STEMI post-cardiac arrest is less clear. METHODS: A retrospective evaluation of a post-cardiac arrest registry was performed. RESULTS: The database consisted of 746 comatose post-cardiac arrest patients including 198 with STEMI (26.5%) and 548 without STEMI (73.5%). Overall survival was greater in those with STEMI compared with those without (55.1% vs. 41.3%; p = 0.001), whereas in all patients who underwent immediate coronary angiography, survival was similar between those with and without STEMI (54.7% vs. 57.9%; p = 0.60). A culprit vessel was more frequently identified in those with STEMI, but also in one-third of patients without STEMI (80.2% vs. 33.2%; p = 0.001). The majority of culprit vessels were occluded (STEMI, 92.7%; no STEMI, 69.2%; p < 0.0001). An occluded culprit vessel was found in 74.3% of STEMI patients and in 22.9% of no STEMI patients. Among cardiac arrest survivors discharged from the hospital who had presented without STEMI, coronary angiography was associated with better functional outcome (93.3% vs. 78.7%; p < 0.003). CONCLUSIONS: Early coronary angiography is associated with improved functional outcome among resuscitated patients with and without STEMI. Resuscitated patients with a presumed cardiac etiology appear to benefit from immediate coronary angiography.

Post-resuscitation intestinal microcirculation: its relationship with sublingual microcirculation and the severity of post-resuscitation syndrome.

OBJECTIVE: Post-resuscitation syndrome has been recognized as one of the major causes of the poor outcomes of cardiopulmonary resuscitation. The aims of this study were to investigate the intestinal microcirculatory changes following cardiopulmonary resuscitation and relate those changes to sublingual microcirculation and the severity of post-resuscitation syndrome as measured by myocardial function and serum inflammatory cytokine levels. METHODS: Twenty-five rats were randomized into three groups: (1) short duration of cardiac arrest (n=10): ventricular fibrillation (VF) was untreated for 4 min prior to 6 min of cardiopulmonary resuscitation (CPR); (2) long duration of cardiac arrest (n=10): VF was untreated for 8 min followed by 8 min of CPR; (3) sham control group (n=5): a sham operation was performed without VF induction and CPR. Intestinal and sublingual microcirculatory blood flow was visualized by a sidestream dark-field (SDF) imaging device at baseline and 1, 2, 4, 6, 8 h post-resuscitation. Myocardial function was measured by echocardiography and serum cytokine levels (TNF-α and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Both intestinal and sublingual microcirculatory blood flow decreased significantly with increasing duration of cardiac arrest and resuscitation. The decreases in intestinal microcirculatory blood flow were closely correlated with the reductions of sublingual microcirculatory blood flow (perfused small vessels density: r=0.772, p<0.01; microcirculatory flow index: r=0.821, p<0.01). The decreased microcirculatory blood flow was closely correlated with weakened myocardial function and elevated inflammatory cytokine levels. CONCLUSIONS: The severity of post-resuscitation intestinal microcirculatory dysfunction is closely correlated with that of myocardial function and inflammatory cytokine levels. The measurement of sublingual microcirculation reflects changes of intestinal microcirculation and may therefore provide a new option for post-resuscitation monitoring.

Post-resuscitation multiple organ dysfunction syndrome: an update / 第二军医大学学报

Post-resuscitation multiple organ dysfunction syndrome(PR-MODS) is a major cause of low survival rate in patients with cardiac arrest.To fully understand the concept of PR-MODS is beneficial for estimating the state of illness,adjusting the therapy and eventually increasing the survival rate.This article reviews the development of PR-MODS concept and compares it with MODS of other causes,including their pathogeny,pathology,mechanism,diagnosis and therapy.