Pathophysiology Of Shock Research Articles

WHERE THE USE BETA-BLOCKER RAISES THE BLOOD PRESSURE

The management of cardiogenic shock is challenging and had high mortality rate. The detailed evaluation of pathophysiology of shock is of paramount important to the correct management. A 70-year-old man presented with sudden dyspnea and chest discomfort on the first postoperative day of incisional

Protocolo de transfusión masiva en obstetricia

La hemorragia obstétrica es la causa más común de mortalidad materna en el mundo. Durante las últimas décadas, nuestro conocimiento de la fisiopatología y manejo del shock hemorrágico se ha incrementado de manera significativa. Una de las estrategias que más impacto ha tenido en la supervivencia de estas pacientes es la transfusión de productos sanguíneos. Debido a ello, es crucial contar con un protocolo de transfusión masiva en caso de hemorragia obstétrica masiva.

Pathophysiology and treatment of hypovolaemia and hypovolaemic shock

Pathophysiology and treatment of hypovolaemia and hypovolaemic shock

Overexpression of GILZ in macrophages limits systemic inflammation while increasing bacterial clearance in sepsis in mice.

Studies support the beneficial effects of glucocorticoids (GCs) during septic shock, steering research toward the potential role of GC-induced proteins in controlling excessive inflammatory responses. GILZ is a glucocorticoid-induced protein involved in the anti-inflammatory effects of GCs. We investigated whether the overexpression of GILZ specifically limited to monocytes and macrophages (M/M) alone could control inflammation, thus improving the outcome of septic shock in animal models. We also monitored the expression of GILZ in M/M from septic mice and septic-shock patients. M/M from patients and septic mice displayed significantly lower expression of GILZ than those isolated from controls. Furthermore, transgenic mice (Tg-mice) experiencing sepsis, with increased expression of GILZ restricted to M/M, showed lower frequencies of inflammatory monocytes than their littermates and lower plasma levels of inflammatory cytokines. Tg-mice also had lower blood bacterial counts. We further established that the upregulation of GILZ in M/M enhanced their phagocytic capacity in in vivo assays. The increase of GILZ in M/M was also sufficient to improve the survival rates of septic mice. These results provide evidence for a central role of both GILZ and M/M in the pathophysiology of septic shock and a possible clue for the modulation of inflammation in this disease.

Teaching "Shock Pathophysiology" by Flipped Classroom: Views and Perspectives.

Flipped classroom (FCR) is an active learning pedagogical method in which the students prepare prior to class using different modalities, for example, reading materials and videos, and afterward spend the time in class discussing the content and reinforcing the concepts. We chose to replace one problem-based case on “Shock” with flipped-style teaching in the respiration circulation module of a private medical university. Our objective was to use the clinical presentation of “Shock” to open a window to interrelate basic science concepts of cardiovascular physiology and pathology. It aimed to merge the case-based discussion with small-group discussions in the form of FCR activity. The qualitative study gives an overview of comments of facilitators, observers, and leadership of the Department and University obtained during focus group discussions and in-depth interviews. Thematic analysis of responses emphasized the importance of FCR as an effective teaching learning modality, which can be made more effective by careful selection of topic and provision of facilities to support technology-enhanced learning. The discussions with facilitators, observers, and leadership revealed its usefulness through student’s engagement and increased participation to build learning of the key concepts. Student satisfaction in these activities can be enhanced by construction of knowledge acquired in non–face-to-face component with substantial pre-reading materials, videos, peer discussions, quizzes, and prompt feedback.

A longitudinal study highlights shared aspects of the transcriptomic response to cardiogenic and septic shock

BackgroundSeptic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. Several studies have described the molecular alterations in SS patients, whereas the molecular factors involved in CS have been poorly investigated. We aimed to assess in the whole blood of CS and SS patients, using septic patients without shock (SC) as controls, transcriptomic modifications that occur over 1 week after ICU admission and are common to the two types of shock.MethodsWe performed whole blood RNA sequencing in 21 SS, 11 CS, and 5 SC. In shock patients, blood samples were collected within 16 h from ICU admission (T1), 48 h after ICU admission (T2), and at day 7 or before discharge (T3). In controls, blood samples were available at T1 and T2. Gene expression changes over time have been studied in CS, SS, and SC separately with a paired analysis. Genes with p value < 0.01 (Benjamini-Hochberg multiple test correction) were defined differentially expressed (DEGs). We used gene set enrichment analysis (GSEA) to identify the biological processes and transcriptional regulators significantly enriched in both types of shock.ResultsIn both CS and SS patients, GO terms of inflammatory response and pattern recognition receptors (PRRs) were downregulated following ICU admission, whereas gene sets of DNA replication were upregulated. At the gene level, we observed that alarmins, interleukin receptors, PRRs, inflammasome, and DNA replication genes significantly changed their expression in CS and SS, but not in SC. Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend.ConclusionsThis pilot study supports, within the limits of a small sample size, the role of alarmins, PRRs, DNA replication, and immunoglobulins in the pathophysiology of circulatory shock, either in the presence of infection or not. We hypothesize that these genes could be potential targets of therapeutic interventions in CS and SS.Trial registrationClinicalTrials.gov, NCT02141607. Registered 19 May 2014.

Abstract 282: Mitochondrial Complex I Induced Myocardial Stunning Following Cardiopulmonary Resuscitation

Background: Cardiogenic shock following cardiopulmonary resuscitation (CPR) for sudden cardiac arrest is common, occurring even in the absence of acute coronary artery occlusion, and contributes to high rates of post-CPR mortality. The pathophysiology of this shock is unclear and effective therapies for improving clinical outcomes are lacking. Methods and Results: Using a murine model of asystolic cardiac arrest, we investigated the pathophysiology of post-CPR cardiogenic shock and discovered that duration of cardiac arrest (4, 8, 12 or 16-minute) prior to CPR determined post-resuscitation success rates, degree of neurological injury, and severity of myocardial dysfunction. Post-CPR cardiac dysfunction was not associated with myocardial necrosis, apoptosis, inflammation, or mitochondrial permeability transition pore opening and recovered within several days, indicative of myocardial stunning. Post-CPR myocardial stunning was associated with increases in ventricular and mitochondrial reactive oxygen species (ROS, P &lt;0.001 vs Sham, respectively). Seahorse micropolarimetry of isolated post-CPR cardiac mitochondria revealed decreased rates of maximal oxygen consumption rates (OCR) for both Complex I and Complex II vs controls ( P &lt;0.01 vs Sham, respectively), indicating inhibition of mitochondrial oxidative phosphorylation. Paradoxically, in the presence of ADP stimulated coupled respiration, post-CRP mitochondria demonstrated increased OCR ( P &lt;0.05 vs Sham) and increased rates of proton leak ( P &lt;0.05 vs Sham), suggesting Complex I as the site of ROS generation. These findings were not observed at complex II. S1QEL, a complex I-specific superoxide inhibitor, administered during CPR, decreased myocardial ROS generation while improving post-CPR myocardial function ( P &lt;0.01 vs CPR control), neurological injury ( P &lt;0.01 vs CPR control), and survival ( P &lt;0.01 vs CPR control). Conclusions: Our results demonstrate that cardiogenic shock following resuscitation from cardiac arrest is consistent with myocardial stunning mediated by mitochondrial complex I injury and ROS generation. Targeting this mechanism represents a novel and practical therapy for improving sudden cardiac arrest resuscitation outcomes.

Lactate and other biomarkers as treatment target in cardiogenic shock.

Cardiogenic shock remains beside sudden cardiac death the most outcome relevant complication of acute myocardial infarction. Over the last two decades as confirmation of the benefit of early revascularization no further relevant improvement in outcome could be achieved. Biomarkers are important for diagnosis, monitoring, and management in cardiogenic shock patients. A bunch of different biomarkers have been associated with prognosis in patients with cardiogenic shock. In routine use standard parameters such as serum lactate or serum creatinine are still most important in monitoring these patients. These established markers outperformed novel markers in prognostic impact in recent trials. Biomarkers serve as important treatment targets and may help physicians in therapeutic decision-making. Furthermore, the complex pathophysiology of cardiogenic shock may be better understood by investigation of different biomarkers.

High-Dose Vitamin B12 in Vasodilatory Shock: A Narrative Review.

Vasodilatory shock, as observed in postoperative states and sepsis, is hallmarked by low systemic vascular resistance and low blood pressure compensated by increased cardiac output. Gasotransmitters, such as nitric oxide and hydrogen sulfide, are implicated in the development and perpetuation of vasodilatory shock. Established therapies do not target these physiologic drivers of vasodilation. Due to their nontoxic and pleotropic effects, micronutrients are being used as rescue therapy in postoperative vasoplegia and septic shock. Here, we outline the pathophysiology of vasodilatory shock, describe the rationale for vitamin B12 (hydroxocobalamin) in vasodilatory shock, and identify literature evaluating its use in vasoplegic states.

Clinical progress of vasopressin in the treatment of septic shock

Septic shock is a serious stage of sepsis with a hospital mortality rate of more than 40%. The pathophysiology of septic shock is vasodilation and increased permeability. Fluid resuscitation, vasopressor drugs are usually used to maintain the perfusion pressure of the main organs. However, infectious patients usually have the irresponsive vessel to catecholamines and may lead to obvious side effects using high doses of norepinephrine or dopamine. Recent studies have shown that vasopressin (AVP) improves hemodynamics, increases tissue perfusion, and synergizes with norepinephrine in patients with septic shock, showing extent application prospects in the treatment of septic shock. The practice of AVP in septic shock is reviewed in this article in order to provide a reference for clinicians.

Septic Shock and the Heart

The aim of this review is to analyze the cardiovascular pathophysiology of septic shock. Using visual representations of a left ventricular cycle in the pressure/volume plane, we describe hemodynamic derangement occurring in septic shock and subsequent changes at each step of treatment allowing a rapid understanding of complex alterations. Acute circulatory failure during sepsis has to be counterbalanced rapidly and appropriately. The most recent guidelines rely on volume expansion, vasoactive, and inotropic support but underlining patients’ pathophysiology is often undetermined. Diagnosis of the hemodynamic substrate needs to be carried out thoroughly, using echocardiography, now commonplace for the intensivist. A pathophysiological approach as we describe might help to understand complicated patterns allowing updates during resuscitation steps. Finally, in our beliefs, clinicians should address septic shock resuscitation using a tailored approach and specific protocols, but their applicability needs to be investigated.

Teaching “Shock Pathophysiology” by Flipped Classroom

Objective:To assess usefulness of flipped style of teaching conducted as small-group format in Cardiovascular and Respiration module for Year-I undergraduate medical students at Aga Khan University.Methods:The study was planned and conducted over a period of eight months from March to October 2017 including the time taken for planning, mock run, execution followed by analysis and dissemination. It was carried out at the Aga Khan University Medical College, Karachi. Pre and post test scores of students after flipped class room sessions was compared. Moreover, perception of students was assessed on Likert scale (0-4) by a pretested validated questionnaire.Results:The mean pre-test scores of the students was 4.86 ± 0.91 which improved to 6.09 ± 0.81 (p = 0.021) after attending the flipped class session. Students approved that the frame work helped to promote their learning motivation and engagement with improvement in understanding of the course materials and enhancement of learning during Face to Face activity.Conclusions:The flipped classroom approach showed promise in teaching and learning of ‘Pathophysiology of Shock’ by clinical scenarios in small group discussions. Implementation of flipped class room activity on a wider scale however needs careful selection of course objectives and logistics.

Prognostic Value of High-sensitivity Troponin I in Patients with Septic Shock: A Prospective Observational Study.

ABSTRACTBackgroundMyocardial dysfunction is one of the mechanisms involved in the pathophysiology of septic shock. The role of troponin as a surrogate of myocardial injury in septic shock is still debated. The aim of this study was to assess the prognostic value of high-sensitivity cardiac troponin I (hs-cTnI) assay in predicting 28-day mortality in patients with septic shock.Materials and MethodsProspective study including 75 patients with septic shock admitted to a medico-surgical ICU from January to December 2017. Patients under the age of 18 years, known pregnancy and patients in post–cardiac arrest were excluded. Clinical and demographic data including age, gender, comorbidities, SAPS II and SOFA scores were collected. Hs-cTnI was measured soon after admission and 12, 24, 48 and 72 after. Receiver operating characteristic (ROC) analysis was performed to identify the most useful troponin I cut-off level for the prediction of 28-day mortality. A p <0.05 was considered significant.ResultsSeventy-five (M/F = 53/22) patients with septic shock were included in the study. The median SOFA and SAPS II scores were 10 and 42, respectively. The median duration of mechanical ventilation was 8 days and the median length of ICU stay was 11 days. The 28-day mortality was 54.6%. We found a high prevalence (47%) of elevated hs-cTnI in patients with septic shock. Median hs-cTnI on admission in the whole group was 36 ng/L. The 28-day mortality was found to be related to age (p <0.001), SAPS II score (p = 0.001), mean arterial pressure (p = 0.038), lactate (p <0.001) and glomerular filtration rate (p <0.001).Hs-cTnI levels were significantly higher in non-survival group than survival one at all time points: H12 (p = 0.006), H24 (p = 0.003), H48 (p = 0.005) and H72 (p=0.001). In multivariate analysis, hs-cTnI at H72 was independently associated with 28-day mortality.ConclusionHs-cTnI elevation at 72 hours was associated with 28-day mortality in septic shock patients.How to cite this articleJendoubi A, Jerbi S, Maamar E, Abbess A, Samoud Z, Kanzari L, et al. Prognostic Value of High-Sensitivity Troponin I in Patients with Septic Shock: A Prospective Observational Study. Indian J Crit Care Med 2019;23(7):320–325.

Cardiogenic shock

Introduction: The cardiogenic shock is a state of endorgan dysfunction, secondary to insufficient cardiac output despite adequate preload, as a result of left ventricular, right ventricular or biventricular dysfunction. Cardiogenic shock occurs in up to 10% of patients presenting with acute myocardial infarction and is the leading cause of death. Objective: To conduct a review of cardiogenic shock. Methodology: The search was performed in the databases PUBMED/MEDLINE, EMBASE and Google Scholar with the search terms: Cardiogenic shock and Epidemiology or Pathophysiology or Diagnosis or Treatment. We selected the most relevant studies on cardiogenic shock. Results: We provided a general description of the definition, epidemiology, clinical manifestations, causes, pathophysiology and treatment of cardiogenic shock. The clinical syndrome of cardiogenic shock has been described as: a systolic blood pressure of less than 90 mm Hg, or greater than 30 mm Hg below baseline BP, for at least 30 minutes, with signs of a reduced cardiac output. The most common cause of cardiogenic shock is acute coronary syndrome, accounting for about 70% to 80% of cardiogenic shock cases. The basic treatment measures include initial stabilization with volume expansion to obtain euvolaemia, vasopressors, and inotropes plus additional therapy for the prevention or treatment of multiorgan system dysfunction. Norepinephrine is associated with fewer arrhythmias and may be the vasopressor of choice in many patients with cardiogenic shock. Coronary reperfusion is the main evidence-based therapeutic intervention for patients with acute MI presenting with cardiogenic shock. Traditionally, intra-aortic balloon pumps have been the main support system, there has been interest in improved mechanical support devices because these may make revascularization safer.

Prehospital clinical presentation in patients with acute coronary syndrome complicated by cardiogenic shock: A single center study

BackgroundThe development of cardiogenic shock remains the most important factor affecting the prognosis of patients with acute coronary syndrome. Despite significant advances in treatment, achieved in the last two decades, the mortality rate is still very high. The development of knowledge about the pathophysiology of cardiogenic shock, necessitates a thorough and comprehensive assessment of its progress at all stages of medical care. ObjectivesThe aim of the study was to assess the prehospital clinical presentation in patients with acute coronary syndrome complicated by cardiogenic shock. MethodsThe population of our study consisted of 40 patients with acute coronary syndrome complicated by cardiogenic shock who were transported to the Intensive Cardiac Therapy Clinic by ambulances directly from place of the event in order to implement primary coronary intervention. The control group was selected among age, gender and infarct location-matched patients with acute coronary syndrome uncomplicated by shock. The clinical presentation in investigated patients was assessed on the basis of the data contained in the medical records of Emergency Medical Services teams. ResultsIn univariate logistic regression analysis eight prehospital clinical symptoms proved to be statistically significant predictors of the development of cardiogenic shock: fainting and/or impaired consciousness, pale skin, cold skin, clammy skin, dyspnea, pulmonary congestion, peripheral cyanosis and hyperglycemia >11,1 mmol/l. In the multivariate model significant predictors of cardiogenic shock development were: pale skin and hyperglycemia >11.1 mmol/l. A risk prediction model was constructed. It proved to differentiate patients from study and control group highly significantly (p < 0.001). ConclusionsPatients with acute coronary syndrome who develop cardiogenic shock, present a different clinical symptoms at the moment of the first medical contact. The proposed 4S Scale can be used for quick assessment of risk in patients with acute coronary syndrome before the development of a fully-blown cardiogenic shock with severe, long-lasting hypotonia.

Microvascular function in healthy volunteers; a comparison of manually and automatically derived measurements

Microcirculatory dysfunction plays a significant role in the pathophysiology of critical illness, including sepsis, haemorrhage and cardiogenic shock. Studies have used video microscopic measurements of the sublingual microcirculation in acute illness, but the clinical utility of these techniques are limited by the need for time-consuming analysis that precludes near-patient data interpretation. The newest video microscopes use Incident Dark Field (IDF) illumination technology (see below) with automated analysis. However the automated analysis has not been validated and there are no data on normal ranges in healthy individuals. This limits the potential application of IDF video microscopy for microcirculation research. This study aims to examine the feasibility and accuracy of measurement of sublingual microvascular function in the awake individual establish the summary statistics of different sublingual microvascular measurements and compare these measurements in three age groups; 18–34 yrs, 35–54 yrs and over 54 yrs. Additionally, this study will correlate the automatically derived measurements of microcirculatory function in comparison to the current gold-standard of manual analysis. An observational study of 150 healthy volunteers, which will include the recording of basic physiological data, medical and drug history, followed by an assessment of the sublingual microvascular bed using CytoCam incident dark field microscopy to measure total vessel density (TVD), perfused vessel density (PVD), and microvascular flow index (MFI). Analysis using current gold standard manual analysis with automated analysis using CytoCam Tool 1.7 (Braedius Medical BV) Analysis plan: (a.) Computation of summary statistics of TVD, PVD, and MFI to determine normal ranges for both manual and automated analysis methods at the population level as well as age-related subgroup level (18-34 yrs, 35-54 yrs and 55 yrs and over). (b.) Estimation of correlation between automatically and manually derived values of TVD, PVD, and MFI within each subject. (c.) Comparison of mean TVD, PVD, and MFI between the age-related subgroup (18-34yrs, 35-54 yrs and 55 yrs and over). Progress: This study has currently recruited 91 of 150 subjects. The procedure of measurement has been found to be well tolerated, with no subjects withdrawing from the study once enrolled. Further, it has been possible, following 2 days of intense work, to train a further member of the team to make reliable, high quality recordings, demonstrating the scope for training those new to the technique to use it in the clinical setting. We look forward to producing full results in the near future.

Neutrophil Activation During Septic Shock.

In addition to their well-known role as the cellular mediators of immunity, key other roles have been identified for neutrophils during septic shock. Importantly, neutrophils indeed play a critical role in the recently described immunothrombosis concept and in septic shock-induced coagulopathy. Septic shock is one of the most severe forms of infection, characterized by an inadequate host response to the pathogenic organism. This host response involves numerous defense mechanisms with an intense cellular activation, including neutrophil activation. Neutrophils are key cells of innate immunity through complex interactions with vascular cells and their activation may participate in systemic tissue damages. Their activation also leads to the emission of neutrophil extracellular traps, which take part in both pathogen circumscription and phagocytosis, but also in coagulation activation. Neutrophils thus stand at the interface between hemostasis and immunity, called immunothrombosis.The present review will develop a cellular approach of septic shock pathophysiology focusing on neutrophils as key players of septic shock-induced vascular cell dysfunction and of the host response, associating immunity and hemostasis. We will therefore first develop the role of neutrophils in the interplay between innate and adaptive immunity, and will then highlight recent advances in our understanding of immunothrombosis septic shock-induced coagulopathy.

Principles of hemodynamics for mechanical circulatory support: patho-physiological key aspects of assisted PCI.

It is essential to understand the pathophysiology of cardiogenic shock and the possible deterioration of contractile function during high-risk PCI in order to select those patients who could benefit from mechanical support thus choosing the most suitable device in every situation. Percutaneous ventricular assist devices (pVAD) provide hemodynamic support by improving cardiac output and mean arterial pressure, but their specific features result in different hemodynamic effects and degrees of myocardial ischemic protection and left ventricle unloading. These features, together with ease of use, specific contraindications and individual risk of complications, must be taken into account in the evaluation and selection of the device. The aim of this review is to illustrate the principles of left ventricular mechanic, including the pressure-volume loop analysis, in order to better understand and to quantify the different hemodynamic effects of pVAD supports and to explain the pathophysiological key aspects of assisted PCI.

Significance of oxygen free radicals in the pathophysiology of hemorrhagic shock – A protocol

Oxygen free radicals have been implicated as the deleterious agent in a variety of organ systems undergoing ischemia and subsequent reperfusion. Hemorrhagic shock represents a clinical situation that carries a high rate of morbidity and mortality despite adequate fluid resuscitation. Since this entity represents, in its most simplified sense, total body ischemia followed by reperfusion, it is likely that the generation of oxygen free radicals has some significance in the pathophysiology of this delayed morbidity. This is a research protocol, where rabbits will be subjected to severe hemorrhagic shock followed by adequate fluid resuscitation. In the first part of the experiment, free radical generation will be measured directly by Electron Paramagnetic Resonance (EPR) spectroscopy in various organ systems in rabbits before and during shock, and following resuscitation. In the second part, free radical scavengers will be introduced as an adjunct to fluid resuscitation in a group of rabbits subjected to hemorrhagic shock to see if mortality rates are affected. By acquiring a better understanding of the molecular mechanisms that may be responsible for the delayed morbidity in reperfusion injury in general, and hemorrhagic shock in particular, we will be able to better address the long-standing problem of multi system organ failure (MSOF) that often follows a successful resuscitation.

Hemorrhagic Shock and the Microvasculature.

The microvasculature plays a central role in the pathophysiology of hemorrhagic shock and is also involved in arguably all therapeutic attempts to reverse or minimize the adverse consequences of shock. Microvascular studies specific to hemorrhagic shock were reviewed and broadly grouped depending on whether data were obtained on animal or human subjects. Dedicated sections were assigned to microcirculatory changes in specific organs, and major categories of pathophysiological alterations and mechanisms such as oxygen distribution, ischemia, inflammation, glycocalyx changes, vasomotion, endothelial dysfunction, and coagulopathy as well as biomarkers and some therapeutic strategies. Innovative experimental methods were also reviewed for quantitative microcirculatory assessment as it pertains to changes during hemorrhagic shock. The text and figures include representative quantitative microvascular data obtained in various organs and tissues such as skin, muscle, lung, liver, brain, heart, kidney, pancreas, intestines, and mesentery from various species including mice, rats, hamsters, sheep, swine, bats, and humans. Based on reviewed findings, a new integrative conceptual model is presented that includes about 100 systemic and local factors linked to microvessels in hemorrhagic shock. The combination of systemic measures with the understanding of these processes at the microvascular level is fundamental to further develop targeted and personalized interventions that will reduce tissue injury, organ dysfunction, and ultimately mortality due to hemorrhagic shock. Published 2018. Compr Physiol 8:61-101, 2018.