While multiple pharmacological drugs have been associated with myocarditis, temporal trends and overall mortality have not been reported. Here we report the spectrum and main features of 5108 reports ...of drug-induced myocarditis, in a worldwide pharmacovigilance analysis, comprising more than 21 million individual-case-safety reports from 1967 to 2020. Significant association between myocarditis and a suspected drug is assessed using disproportionality analyses, which use Bayesian information component estimates. Overall, we identify 62 drugs associated with myocarditis, 41 of which are categorized into 5 main pharmacological classes: antipsychotics (n = 3108 reports), salicylates (n = 340), antineoplastic-cytotoxics (n = 190), antineoplastic-immunotherapies (n = 538), and vaccines (n = 790). Thirty-eight (61.3%) drugs were not previously reported associated with myocarditis. Antipsychotic was the first (1979) and most reported class (n = 3018). In 2019, the two most reported classes were antipsychotics (54.7%) and immunotherapies (29.5%). Time-to-onset between treatment start and myocarditis is 15 interquartile range: 10; 23 days. Subsequent mortality is 10.3% and differs between drug classes with immunotherapies the highest, 32.5% and salicylates the lowest, 2.6%. These elements highlight the diversity of presentations of myocarditis depending on drug class, and show the emerging role of antineoplastic drugs in the field of drug-induced myocarditis.
Background
Prone positioning (PP) during veno-venous ECMO is feasible, but its physiological effects have never been thoroughly evaluated. Our objectives were to describe, through electrical ...impedance tomography (EIT), the impact of PP on global and regional ventilation, and optimal PEEP level.
Methods
A monocentric study conducted on ECMO-supported severe ARDS patients, ventilated in pressure-controlled mode, with 14-cmH
2
O driving pressure and EIT-based “optimal PEEP”. Before, during and after a 16-h PP session, EIT-based distribution and variation of tidal impedance, VT
dorsal
/VT
global
ratio, end-expiratory lung impedance (EELI) and static compliance were collected. Subgroup analyses were performed in patients who increased their static compliance by ≥ 3 mL/cmH
2
O after 16 h of PP.
Results
For all patients (
n
= 21), tidal volume and EELI were redistributed from ventral to dorsal regions during PP. EIT-based optimal PEEP was significantly lower in PP than in supine position. Median (IQR) optimal PEEP decreased from 14 (12–16) to 10 (8–14) cmH
2
O. Thirteen (62%) patients increased their static compliance by ≥ 3 mL/cmH
2
O after PP on ECMO. This subgroup had higher body mass index, more frequent viral pneumonia, shorter ECMO duration, and lower baseline VT
dorsal
/VT
global
ratio than patients with compliance ≤ 3 mL/cmH
2
O (
P
< 0.01).
Conclusion
Although baseline tidal volume distribution on EIT may predict static compliance improvement after PP on ECMO, our results support physiological benefits of PP in all ECMO patients, by modifying lung mechanics and potentially reducing VILI. Further studies, including a randomized–controlled trial, are now warranted to confirm potential PP benefits during ECMO.
Despite quick implementation of reperfusion therapies, a few patients with high-risk, acute, massive, pulmonary embolism (PE) remain highly hemodynamically unstable. Others have absolute ...contraindication to receive reperfusion therapies. Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) might lower their right ventricular overload, improve hemodynamic status, and restore tissue oxygenation.
ECMO-related complications and 90-day mortality were analyzed for 17 highly unstable, ECMO-treated, massive PE patients admitted to a tertiary-care center (2006-2015). Hospital- discharge survivors were assessed for long-term health-related quality of life. A systematic review of this topic was also conducted.
Seventeen high-risk PE patients median age 51 (range 18-70) years, Simplified Acute Physiology Score II (SAPS II) 78 (45-95) were placed on VA-ECMO for 4 (1-12) days. Among 15 (82%) patients with pre-ECMO cardiac arrest, seven (41%) were cannulated during cardiopulmonary resuscitation, and eight (47%) underwent pre-ECMO thrombolysis. Pre-ECMO median blood pressure, pH, and blood lactate were, respectively: 42 (0-106) mmHg, 6.99 (6.54-7.37) and 13 (4-19) mmol/L. Ninety-day survival was 47%. Fifteen (88%) patients suffered in-ICU severe hemorrhages with no impact on survival. Like other ECMO-treated patients, ours reported limitations of all physical domains but preserved mental health 19 (4-69) months post-ICU discharge.
VA-ECMO could be a lifesaving rescue therapy for patients with high-risk, acute, massive PE when thrombolytic therapy fails or the patient is too sick to benefit from surgical thrombectomy. Because heparin-induced clot dissolution and spontaneous fibrinolysis allows ECMO weaning within several days, future studies should investigate whether VA-ECMO should be the sole therapy or completed by additional mechanical clot-removal therapies in this setting.
Purpose
The frequency of neurological events and their impact on patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) are unknown. We therefore study the epidemiology, risk ...factors, and impact of cerebral complications occurring in VV-ECMO patients.
Methods
Observational study conducted in a tertiary referral center (2006–2012) on patients developing a neurological complication (ischemic stroke or intracranial bleeding) while on VV-ECMO versus those who did not, and a systematic review on this topic.
Results
Among 135 consecutive patients who had received VV-ECMO, 18 (15 assessable) developed cerebral complications on ECMO: cerebral bleeding in 10 (7.5 %), ischemic stroke in 3 (2 %), or diffuse microbleeds in 2 (2 %), occurring after respective medians (IQR) of 3 (1–11), 21 (10–26), and 36 (8–63) days post-ECMO onset. Intracranial bleeding was independently associated with renal failure at intensive care unit admission and rapid PaCO
2
decrease at ECMO initiation, but not with age, comorbidities, or hemostasis disorders. Seven (70 %) patients with intracranial bleeding and one (33 %) with ischemic stroke died versus 40 % of patients without neurological event. A systematic review found comparable intracranial bleeding rates (5 %).
Conclusions
Neurological events occurred frequently in patients on VV-ECMO. Intracranial bleeding, the most frequent, occurred early and was associated with higher mortality. Because it was independently associated with rapid hypercapnia decrease, the latter should be avoided at ECMO onset, but its exact role remains to be determined. These findings may have major implications for the care of patients requiring VV-ECMO.
Ventilator settings for patients with severe acute respiratory distress syndrome supported by venovenous extracorporeal membrane oxygenation are currently set arbitrarily. The impact on serum and ...pulmonary biotrauma markers of the transition to ultra-protective ventilation settings following extracorporeal membrane oxygenation implantation, and different mechanical ventilation strategies while on extracorporeal membrane oxygenation were investigated.
Randomized clinical trial.
Nine-month monocentric study.
Severe acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation.
After starting extracorporeal membrane oxygenation, patients were switched to the bi-level positive airway pressure mode with 1 second of 24 cm H2O high pressure and 2 seconds of 12 cm H2O low pressure for 24 hours. A computer-generated allocation sequence randomized patients to receive each of the following three experimental steps: 1) high pressure 24 cm H2O and low pressure 20 cm H2O (very high positive end-expiratory pressure-very low driving pressure); 2) high pressure 24 cm H2O and low pressure 5 cm H2O (low positive end-expiratory pressure-high driving pressure); and 3) high pressure 17 cm H2O and low pressure 5 cm H2O (low positive end-expiratory pressure-low driving pressure). Plasma and bronchoalveolar lavage soluble receptor for advanced glycation end-products, plasma interleukin-6, and monocyte chemotactic protein-1 were sampled preextracorporeal membrane oxygenation and after 12 hours at each step.
Sixteen patients on ECMO after 7 days (1-11 d) of mechanical ventilation were included. "Ultra-protective" mechanical ventilation settings following ECMO initiation were associated with significantly lower plasma sRAGE, interleukin-6, and monocyte chemotactic protein-1 concentrations. Plasma sRAGE and cytokines were comparable within each on-ECMO experimental step, but the lowest bronchoalveolar lavage sRAGE levels were obtained at minimal driving pressure.
ECMO allows ultra- protective ventilation, which combines significantly lower plateau pressure, tidalvolume, and driving pressure. This ventilation strategy significantly limited pulmonary biotrauma, which couldtherefore decrease ventilator-induced lung injury. However, the optimal ultra-protective ventilation strategy once ECMO is initiated remains undetermined and warrants further investigations. (Crit Care Med 2019; 47:1505-1512).
Patients with sepsis-induced cardiomyopathy with cardiogenic shock have a high mortality. This study assessed venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for sepsis-induced ...cardiogenic shock refractory to conventional treatments.
In this retrospective, multicentre, international cohort study, we compared outcomes of 82 patients (aged ≥18 years) with septic shock who received VA-ECMO at five academic ECMO centres, with 130 controls (not receiving ECMO) obtained from three large databases of septic shock. All patients had severe myocardial dysfunction (cardiac index 3 L/min per m2 or less or left ventricular ejection fraction LVEF 35% or less) and severe haemodynamic compromise (inotrope score at least 75 μg/kg per min or lactic acidaemia at least 4 mmol/L) at time of inclusion. The primary endpoint was survival at 90 days. A propensity score-weighted analysis was done to control for confounders.
At baseline, patients treated with VA-ECMO had more severe myocardial dysfunction (mean cardiac index 1·5 L/min per m2vs 2·2 L/min per m2, LVEF 17% vs 27%), more severe haemodynamic impairment (inotrope score 279 μg/kg per min vs 145 μg/kg per min, lactataemia 8·9 mmol/L vs 6·5 mmol/L), and more severe organ failure (Sequential Organ Failure Assessment score 17 vs 13) than did controls, with p<0·0001 for each comparison. Survival at 90 days for patients treated with VA-ECMO was significantly higher than for controls (60% vs 25%, risk ratio RR for mortality 0·54, 95% CI 0·40–0·70; p<0·0001). After propensity score weighting, ECMO remained associated with improved survival (51% vs 14%, adjusted RR for mortality 0·57, 95% CI 0·35–0·93; p=0·0029). Lactate and catecholamine clearance were also significantly enhanced in patients treated with ECMO. Among the 49 survivors treated with ECMO, 32 who had been treated at the largest centre reported satisfactory Short Form-36 evaluated health-related quality of life at 1-year follow-up.
Patients with severe sepsis-induced cardiogenic shock treated with VA-ECMO had a large and significant improvement in survival compared with controls not receiving ECMO. However, despite the careful propensity-weighted analysis, we cannot rule out unmeasured confounders.
None.
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