Management of cardiogenic shock: a narrative review.

Cardiogenic shock (CS) is characterized by low cardiac output and sustained tissue hypoperfusion that may result in end-organ dysfunction and death. CS is associated with high short-term mortality, and its management remains challenging despite recent advances in therapeutic options. Timely diagnosis and multidisciplinary team-based management have demonstrated favourable effects on outcomes. We aimed to review evidence-based practices for managing patients with ischemic and non-ischemic CS, detailing the multi-organ supports needed in this critically ill patient population.

Association of Sepsis With Neurologic Outcomes of Adult Patients Treated With Venoarterial Extracorporeal Membrane Oxygnenation.

OBJECTIVES: Neurologic outcomes of patients under venoarterial extracorporeal membrane oxygenation (VA-ECMO) may be worsened by secondary insults of systemic origin. We aimed to assess whether sepsis, commonly observed during ECMO support, is associated with brain injury and outcomes. DESIGN: Single-center cohort study of the "exposed-non-exposed" type on consecutive adult patients treated by VA-ECMO. SETTING: Medical ICU of a university hospital, France, 2013-2020. PATIENTS: Patients with sepsis at the time of VA-ECMO cannulation ("sepsis" group) were compared with patients without sepsis ("no sepsis" group). The primary outcome measure was poor functional outcome at 90 days, defined by a score greater than or equal to 4 on the modified Rankin scale (mRS), indicating severe disability or death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 196 patients were included ("sepsis," n = 128; "no sepsis," n = 68), of whom 87 (44.4%) had presented cardiac arrest before VA-ECMO cannulation. A poor functional outcome (mRS ≥ 4) was observed in 99 of 128 patients (77.3%) of the "sepsis" group and 46 of 68 patients (67.6%) of the "no sepsis" group (adjusted logistic regression odds ratio (OR) 1.21, 95% CI, 0.58-2.47; inverse probability of treatment weighting (IPTW) OR 1.24; 95% CI, 0.79-1.95). Subsequent analyses performed according to pre-ECMO cardiac arrest status suggested that sepsis was independently associated with poorer functional outcomes in the subgroup of patients who had experienced pre-ECMO cardiac arrest (adjusted logistic regression OR 3.44; 95% CI, 1.06-11.40; IPTW OR 3.52; 95% CI, 1.68-7.73), whereas no such association was observed in patients without pre-ECMO cardiac arrest (adjusted logistic regression OR 0.69; 95% CI, 0.27-1.69; IPTW OR 0.76; 95% CI, 0.42-1.35). Compared with the "no sepsis" group, "sepsis" patients presented a significant increase in S100 calcium-binding protein beta concentrations at day 1 (0.94 µg/L vs. 0.52 µg/L, p = 0.03), and more frequent EEG alterations (i.e., severe slowing, discontinuous background, and a lower prevalence of sleep patterns), suggesting brain injury. CONCLUSION: We observed a detrimental role of sepsis on neurologic outcomes in the subgroup of patients who had experienced pre-ECMO cardiac arrest, but not in other patients.

Diagnostic yield, safety and therapeutic consequences of myocardial biopsy in clinically suspected fulminant myocarditis unweanable from mechanical circulatory support.

BACKGROUND: Fulminant myocarditis is a rare and severe disease whose definite and etiological diagnoses rely on pathological examination. Albeit, myocardial biopsy can be associated with significant morbidity and mortality, its therapeutic consequences are unclear. We conducted a study to determine the diagnostic yield, the safety and the therapeutic consequences of myocardial biopsy in patients with fulminant clinically suspected myocarditis unweanable from mechanical circulatory support (MCS). METHODS: Monocenter, retrospective, observational cohort study in a 26-bed French tertiary ICU between January 2002 and February 2019. Inclusion of all fulminant clinically suspected myocarditis patients undergoing in-ICU myocardial biopsy while being on MCS. The primary endpoint was the proportion of patients classified as definite myocarditis using Bonaca criteria before and after including myocardial biopsy results. RESULTS: Forty-seven patients (median age 41 [30-47], female 53%) were included: 55% died before hospital discharge, 34% could be bridged-to-recovery and 15% bridged-to-transplant. Myocardial biopsy was endomyocardial or surgical in 36% and 64% cases respectively. Tamponade requiring emergency pericardiocentesis occurred in 29% patients after endomyocardial biopsy. After adding the biopsy results in the Bonaca classification algorithm the percentage of definite myocarditis raised from 13 to 55% (p < 0.0001). The rate of biopsy-related treatments modifications was 13%, leading to patients' recovery in only 4% patients. CONCLUSIONS: In clinically suspected myocarditis unweanable from MCS, myocardial biopsy increased the rate of definite myocarditis but was associated with a low rate of treatment modification and a significant proportion of adverse events. We believe the benefit/risk ratio of myocardial biopsy should be more carefully weighted in these frail and selected patients than suggested by actual guidelines. Further prospective studies are now needed to determine its value in patients under MCS.

Epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation shock.

PURPOSE: Whether epinephrine or norepinephrine is preferable as the continuous intravenous vasopressor used to treat post-resuscitation shock is unclear. We assessed outcomes of patients with post-resuscitation shock after out-of-hospital cardiac arrest according to whether the continuous intravenous vasopressor used was epinephrine or norepinephrine. METHODS: We conducted an observational multicenter study of consecutive patients managed in 2011-2018 for post-resuscitation shock. The primary outcome was all-cause hospital mortality, and secondary outcomes were cardiovascular hospital mortality and unfavorable neurological outcome (Cerebral Performance Category 3-5). A multivariate regression analysis and a propensity score analysis were performed, as well as several sensitivity analyses. RESULTS: Of the 766 patients included in five hospitals, 285 (37%) received epinephrine and 481 (63%) norepinephrine. All-cause hospital mortality was significantly higher in the epinephrine group (OR 2.6; 95%CI 1.4-4.7; P = 0.002). Cardiovascular hospital mortality was also higher with epinephrine (aOR 5.5; 95%CI 3.0-10.3; P < 0.001), as was the proportion of patients with CPC of 3-5 at hospital discharge. Sensitivity analyses produced consistent results. The analysis involving adjustment on a propensity score to control for confounders showed similar findings (aOR 2.1; 95%CI 1.1-4.0; P = 0.02). CONCLUSION: Among patients with post-resuscitation shock after out-of-hospital cardiac arrest, use of epinephrine was associated with higher all-cause and cardiovascular-specific mortality, compared with norepinephrine infusion. Until additional data become available, intensivists may want to choose norepinephrine rather than epinephrine for the treatment of post-resuscitation shock after OHCA.

Myocardial dysfunction after cardiac arrest: tips and pitfalls.

Postcardiac arrest shock (PCAS) is defined by hemodynamic instability occurring in the first hours after cardiac arrest (CA) and is a major cause of mortality among patients hospitalized after CA. It includes vasoplegia and myocardial dysfunction. This postcardiac arrest myocardial dysfunction is supposed to recover within the 3 days. However, there are many unknowns regarding its definition, its prognosis value and its management. In this review dedicated to emergency physicians, we choose to address tips and pitfalls they should know regarding this prevalent syndrome.

In-hospital cardiac arrests admitted alive in intensive care units: Insights from the CubRéa database.

BACKGROUND: In-hospital cardiac arrest(IHCA) has received little attention compared with out-of-hospital cardiac arrest. AIM: To address the paucity of data on IHCA patients, we examined key features, variations in mortality and predictors of death among patients admitted in French intensive care units(ICUs) from 1997 to 2015. METHODS: Using the database of the Collège des Utilisateurs de Bases de données en Réanimation(CUB-Réa) that prospectively collects data from ICUs in the greater Paris area, we determined temporal trends in the incidence of IHCA, patients' outcomes, crude and Simplified Acute Physiology Score(SAPS)-II Standardized mortality and predictors of in-ICU mortality. RESULTS: Of the 376,325 ICU admissions, 15,324(4.08%) had IHCA, with incidence increasing from 2.78% to 3.83%(p < 0.001). Over time, the patient age increased by 0.7 years(p = 0.04) and SAPS-II increased by 2.3%(p < 0.001). Crude in-ICU mortality decreased from 78% to 62.5% over the past 18 years(p < 0.001). The SAPS-II-standardized mortality also decreased over time from 78.4% to 68.3%(p < 0.001) representing a 10.1% relative decrease from 1997 to 2015. In multivariate analysis, admission in a more recent time-period was an independent correlate of decreased mortality(OR 0.40, 95%CI 0.35-0.46). CONCLUSION: Occurrence of IHCA increased over time but remains an uncommon reason for being admitted to ICU. From 1997 to 2015, we observed a change in patient profile, with older and more critically ill patients, despite which in-ICU mortality has substantially decreased in IHCA patients, likely resulting from a global improvement in the process of care and more widespread implementation of rapid response teams.

Identifying early indicators of secondary peritonitis in critically ill patients with cirrhosis.

Ascitic fluid infection (AFI) is a life-threatening complication of cirrhosis. We aimed to identify early indicators of secondary peritonitis (SP), which requires emergency surgery, and to describe the outcomes of SP and spontaneous bacterial/fungal peritonitis (SBFP). Adults with cirrhosis and AFI admitted to 16 university or university-affiliated ICUs in France between 2002 and 2017 were studied retrospectively. Cases were identified by searching the hospital databases for relevant ICD-10 codes and hospital charts for AFI. Logistic multivariate regression was performed to identify factors associated with SP. Secondary outcomes were short- and long-term mortality and survivors' functional outcomes. Of 178 included patients (137 men and 41 women; mean age, 58 ± 11 years), 21 (11.8%) had SP, confirmed by surgery in 16 cases and by abdominal computed tomography in 5 cases. Time to diagnosis exceeded 24 h in 7/21 patients with SP. By multivariate analysis, factors independently associated with SP were ascitic leukocyte count > 10,000/mm3 (OR 3.70; 95%CI 1.38-9.85; P = 0.009) and absence of laboratory signs of decompensated cirrhosis (OR 4.53; 95%CI 1.30-15.68; P = 0.017). The 1-year mortality rates in patients with SBFP and SP were 81.0% and 77.5%, respectively (Log-rank test, P = 0.92). Patients with SP vs. SBFP had no differences in 1-year functional outcomes. This multicenter retrospective study identified two indicators of SP as opposed to SBFP in patients with cirrhosis. Using these indicators may help to provide early surgical treatment.

Case Report: Takotsubo Syndrome Associated With Novel Coronavirus Disease 2019.

Background: Takotsubo cardiomyopathy is triggered by emotional or physical stress. It is defined as a reversible myocardial dysfunction, usually with apical ballooning aspect due to apical akinesia associated with hyperkinetic basal left ventricular contraction. Described in cases of viral infections such as influenza, only few have been reported associated with novel coronavirus disease 2019 (COVID-19) in the recent pandemic. Case summary: A 79-years-old man, with cardiovascular risk factors (type 2 diabetes and hypertension) and chronic kidney disease, presented to the emergency room for severe dyspnea after 8 days of presenting respiratory symptoms and fever. Baseline electrocardiogram (ECG) was normal, but he presented marked inflammatory syndrome. He was transferred to an intensive care unit to receive mechanical ventilation within 6 h, due to acute respiratory distress syndrome. He presented circulatory failure 2 days after, requiring norepinephrine support (up to up to 1.04 µg/kg/min). Troponin T was elevated (637 ng/l). ECG showed diffuse T wave inversion. Echocardiography showed reduced left ventricular ejection fraction (LVEF 40%), with visual signs of Takotsubo cardiomyopathy. Cardiac failure resolved after 24 h with troponin T decrease (433 ng/l) and restoration of cardiac function (LVEF 60% with regression of Takotsubo features). Patient died after 15 days of ICU admission, due to septic shock from ventilator-acquired pneumonia. Cardiac function was then normal. Conclusion: Mechanisms of Takotsubo cardiomyopathy in viral infections include catecholamine-induced myocardial toxicity and inflammation related to sepsis. Differential diagnoses include myocarditis and myocardial infarction. Evidence of the benefit of immunomodulatory drugs and dexamethasone are growing to support this hypothesis in COVID-19.

Transplant rejections associated with immune checkpoint inhibitors: A pharmacovigilance study and systematic literature review.

BACKGROUND: Solid organ transplant recipients are at increased risk of cancer due to long-term immunosuppression. Immune-checkpoint inhibitors (ICI) showed clinical benefits but increased risk of transplant rejection. Our work aims to assess the main features of reported rejection events. METHODS: A disproportionality analysis of the World Health Organisation pharmacovigilance database, VigiBase, to identify drugs associated with rejection events. The estimate of this analysis is the information component for which the lower end of the 95% credibility interval (IC025) indicates significance when positive. We combined a systematic literature review of case reports to obtain additional information regarding treatment management and histopathological findings. RESULTS: A total of 96 reports of transplant rejections following ICI were included, including kidney (n = 65), liver (n = 23), cornea (n = 2) and heart (n = 5). The main indication reported for ICI was malignant melanoma (39/89, 43.8%). The time to onset between first ICI administration and rejection was 21 [interquartile range: 13; 56] days. Kidney transplant rejection was associated with nivolumab (IC025 = 1.32), pembrolizumab (IC025 = 1.17) and ipilimumab (IC025 = 0.33); while liver transplant rejection was mostly over-reported with nivolumab (IC025 = 1.95). Overall, anti-PD-1 and anti-PD-L1 were more involved than anti-CTLA-4 drugs (93.0% versus 7.0%). Subsequent mortality was 36.5% and involved liver-transplant recipients more than other organ recipients (p < 0.0001). When performed, all biopsies reported acute cellular rejections, but only a few showed concomitant antibody-mediated lesions (6/28, 21.4%). Management mainly consisted in intravenous corticosteroid boluses and ICI cessation. CONCLUSION: ICI-associated transplant rejections were mostly reported in kidney and liver transplant recipients. Rejections were T-cell mediated with low participation of humoral response.

Trends in cardiogenic shock complicating acute myocardial infarction.

AIMS: Few studies describe recent changes in the prevalence, management, and outcomes of cardiogenic shock (CS) patients complicating acute myocardial infarction (AMI) in the era of widespread use of invasive strategies. The aim of the present study was to analyse trends observed in CS complicating AMI over the past 10 years, focusing on the timing of CS occurrence (i.e. primary CS, CS on admission vs. secondary CS, CS developed subsequently during hospitalization). METHODS AND RESULTS: Three nationwide French registries conducted and designed to evaluate AMI management and outcomes in 'real-life' practice included consecutive AMI patients (n = 9951) admitted to intensive cardiovascular care units (ICCUs) over a 1-month period, 5 years apart. The prevalence of CS complicating AMI decreased from 2005 to 2015: 5.9%, mean age 74.1 ± 12.7 in 2005; 4.0%, mean age 73.9 ± 12.7 in 2010, 2.8%, mean age 71.1 ± 15.0 in 2015 (P < 0.001). It decreased for both primary (1.8% to 1.0%) and secondary CS (4.1% to 1.8%). The profile of CS patients also changed over time with more patients presenting out-of-hospital cardiac arrest. In both primary and secondary CS, the use of percutaneous coronary intervention increased markedly over time, as did the use of mechanical ventilation and cardiac assist devices. Over the 10-year period, in-hospital mortality remained unchanged for both primary CS (41.8% to 37.8%) or secondary CS (57.3% to 58.8%). However, 1-year mortality decreased in patients with primary CS (from 60% to 37.8%, P = 0.038), and remained unchanged in patients developing secondary CS (from 64.5% to 69.1%, P = 0.731). CONCLUSION: Cardiogenic shock complicating AMI has become less frequent but, if present, CS, and particularly secondary CS, carries a very high mortality, which has not substantially improved over the past 10 years, in spite of the more frequent use of invasive strategies.

Impact of hyperoxia on patients hospitalized in an intensive care unit for acute heart failure.

BACKGROUND: Oxygen therapy remains a cornerstone of treatment for acute heart failure in patients with pulmonary congestion. While avoiding hypoxaemia has long been a goal of critical care practitioners, less attention has been paid to the potential hazard related to excessive hyperoxia. AIM: To evaluate the impact of early hyperoxia exposure among critically ill patients hospitalized in an intensive care unit for acute heart failure. METHODS: In this preliminary study conducted in a Parisian intensive care unit, we assessed patients with acute heart failure admitted with pulmonary congestion and treated with oxygen therapy from 1 January 2015 to 31 December 2016. The hyperoxia group was defined by having at least one partial pressure of oxygen measurement>100mmHg on the first day following admission to the intensive care unit. The primary endpoint was 30-day all-cause mortality. Secondary endpoints were 30-day unplanned hospital admissions, occurrence of infections and intensive care unit and hospital lengths of stay. RESULTS: Seventy-five patients were included. Forty-three patients (57.3%) presented hyperoxia, whereas 32 patients (42.7%) did not (control group). The baseline clinical characteristics did not differ between the two groups. The primary endpoint was not statistically different between the two groups (14.0% in the hyperoxia group vs 18.8% in the control group; P=0.85). The secondary endpoints were also not significantly different between the two groups. In the multivariable analysis, hyperoxia was not associated with increased 30-day mortality (odds ratio 0.77, 95% confidence interval 0.24-2.41). CONCLUSION: In patients referred to an intensive care unit for acute heart failure, we did not find any difference in outcomes according to the presence of hyperoxia.

The (Fab)ulous Destiny of Idarucizumab: Highlighting Its Interference with Urine Protein Immunofixation.

Idarucizumab is a humanized antigen binding fragment (Fab) of a recombinant anti-dabigatran monoclonal antibody (IgG1-kappa) that allows rapid and sustained reversal of dabigatran-induced anticoagulation in case of bleeding or urgent surgery. Herein, we report a very unusual case of dabigatran reversal by idarucizumab in a 79-year-old woman with acute kidney failure admitted to a hospital in a context of hemoptysis. Three repeated injections were necessary because of massive dabigatran overdose and high rebounds of dabigatran plasma concentration. Idarucizumab was found on urine immunofixation up to 6 days after the last injection where it reacted with anti-kappa light chain antibody, but not with anti-gamma heavy chain antibody. Physicians should be aware of the increased half-life of idarucizumab in this context of acute kidney impairment and of its interference with urine immunofixation because it could lead to false-positive results and misdiagnosis of a paraprotein.

Weaning from veno-arterial extra-corporeal membrane oxygenation: which strategy to use?

Refractory cardiogenic shock patients may be rescued by veno-arterial extracorporeal membrane oxygenation (VA ECMO). After a few days of mechanical assistance, the device can sometimes be successfully removed if the patient has partially or fully recovered from the condition that required the use of ECMO. The percentage of patients with refractory cardiogenic shock who are successfully weaned from ECMO varies from 31% to 76%. Weaning does not mean survival, because 20% to 65% of patients weaned from VA ECMO support do not survive to hospital discharge. The high death rate after successful weaning shows that many questions remain unresolved in this field. In this review, we will discuss the various factors influencing survival and a successful weaning from VA ECMO, in addition to weaning approaches proposed in the literature. Based on this information, we will propose a strategy to optimize the weaning process.

Understanding Left Ventricular Assist Devices.

BACKGROUND/AIMS: Long-term mechanical assist devices are now commonly used in the treatment of severe heart failure to unload the failing ventricle, maintain sufficient end-organ perfusion and improve functional capacity. Depending on the assisted ventricles, 3 categories of long-term assist devices are available: left ventricular assist device (LVAD), biventricular assist device and total artificial heart. Improvements in technology, especially the advent of smaller, durable continuous flow pumps, have led to the use of LVADs in a much broader population of patients in the last 10 years. Both the number of patients living with LVADs and the life expectancy of these patients are increasing. Regarding this growing number of patients with LVAD, intensivists need to understand the physiology of the devices, their functioning, potential complications and their management. METHODS: We performed a narrative review of relevant medical literature regarding the physiology of patients with LVAD and management of common complications relevant to the critical care physicians. RESULTS: The most frequent complications occurring in the LVAD patients after the post-operative period are bleeding, driveline infections, thrombosis, device malfunction, right ventricular failure and arrhythmias. Bleeding is the most frequent adverse event in LVAD due to a combination of anticoagulation and acquired von Willebrand disease secondary to shear stress produced within the pump. Their management includes antiplatelet therapy arrest, reduction of the anticoagulation regimen and specific therapy if feasible. Infection is the second most common cause of death after cardiac failure in LVAD patients. All infections must be aggressively treated to avoid seeding the device. Device thrombosis can develop even when patients are adequately anticoagulated and taking antiplatelet therapy because the LVAD is responsible for a chronic hypercoagulable state. CONCLUSION: Management of these unique patients in the ICU is best accomplished with a multidisciplinary team that includes specialists in advanced heart failure, LVAD nurse coordinators and intensivists.