Quarterly EJEM research round-up - June 2024

Welcome to the quarterly EJEM research round-up, where we present our top picks from the last three months of EJEM editions.

Chiara Lazzeri, Associate Editor

Verdonschot et al [1]performed a retrospective two-centre study to investigate the number of in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA) patients eligible to Extracorporeal Cardiopulmonary Resuscitation (ECPR). Clinical characteristics that may help to identify which patients benefit the most from ECPR were also detected. The study population comprised all IHCA and OHCA patients screened for eCPR between 1 January 2017 and 1 January 2020 in Rotterdam, the Netherlands. The features of this investigation are the large population included and the organizational characteristics of the Netherlands. This country, small and densly populated, is characterized by a short travel time to the hospital and the existence of is a nationwide response system exists that alerts trained citizens when an OHCA occurs in their neighbourhood. That is probably why in Netherlands the use of Automated External Defibrillator (AED) (29-65%) is higher than in other countries....

 The inclusion criteria according to the local protocol were: age ≤ 70 years, no ROSC before arrival at the ED for OHCA patients, witnessed arrest or signs of life within 5min (e.g. movement or breathing), no-flow duration of ≤ 5min, CPR duration ≥ 20 min, activities of daily living (ADL) independent before cardiac arrest. Patients who were eligible to ECPR, either treated with conventional Cardiopulmonary Resuscitation (CCPR) or ECPR, were included in the analysis. Of the 412 IHCA patients who were screened for eligibility to ECPR, 41 (10.0%) were eligible to ECPR. Of these, 21 (51.2%) received CCPR and 20 (48.8%) received ECPR. Of the patients eligible to ECPR, 14 (34.1%) were treated in the hospital without ECPR facilities. Of the 27 patients eligible to ECPR in the hospital with ECPR facilities, 20 (74.1%) were actually treated with ECPR. In total, 867 OHCA patients were screened for eligibility of whom 83 (9.6%) were eligible to ECPR. Of these, 60 (72.3%) received CCPR and 23 (27.7%) received ECPR. Of the 73 patients eligible to ECPR in the hospital with ECPR facilities, 23 (31.5%) were actually treated with ECPR. The main finding of the investigation by Verdonschot  et al [1] is an ECPR eligibility rate of 10.0% for IHCA, and 9.6% for OHCA patients, in keeing with available evidence and, more importantly, that less than half of these patients eligible to ECPR were actually treated with ECPR in both IHCA and OHCA. The Authors hypothesized that an equal eligibility percentage (between OHCA and IHCA) may be related to  the high number of AED use observed in the Netherlands, resulting in a higher number of ROSC pre-hospital with no need of ECPT, in combination with shorter travel times.  Stricter criteria for eCPR eligibility in local protocols may also account for this finidng.

Another interesting finding of the investigation by Verdonschot et al [1] is that, while  48.8% of the IHCA patients eligible to ECPR were actually treated with ECPR, only 27.7% of the OHCA ECPR patients were actually treated with ECPR. The Authorsadmitted that the reason(s) why why these patients were not treated with ECPR  were unclear, given the retrospective design of this study. 

The investigation by Verdonschot et al [1] addresses the hot topic of eCPR eligibility in IHCA and OHCA. Overall the results of their investigation strongly support the notion that local registries are needed to analyze this phenomenon due to differences in inclusion criteria and local organization of emergency care.

Usategui-Martín et al [2] aimed to determine how hypoglycemia, normoglycemia, and hyperglycemia modify the predictive ability of lactate for short-term mortality (3 days) in a prospective observational study (October 2018-Decembre 2022). This investigation is a . multicenter, EMS-delivery, ambulance-based study, considering 38 basic life support units and 5 advanced life support units referring to four tertiary care hospitals in Spain. Adults recruited from among all phone requests for emergency assistance who were later evacuated to emergency departments  were considered eligible. In the study by Usategui-Martín et a [2] a total of 6341 participants fulfilled the inclusion criteria, mainly males (59%). The 3-day in-hospital mortality (for any cause) rate was 3.5%. The predictive capacity of lactate for 3-day mortality was only significantly different between normo-glycemia and hyperglycemia. The best predictive result was for normoglycemia – AUC = 0.897 (95% CI: 0.881–0.913) – then hyperglycemia – AUC = 0.819 (95% CI: 0.770–0.868) and finally, hypoglycemia – AUC = 0.703 (95% CI: 0.422–0.983). The secondary objective was to evaluate the predictive ability of lactate in diabetic patients. The rationale of this secondary objective is that increased lactate production is frequent in noncontrolled diabetic patients, being associated with a reduced aerobic oxidative capacity and with restricted lactate transport. However, in this study the stratification according to diabetes presented no statistically significant difference.The novelties of this investigation are the population enrolled (adults recruited from emergency assistance) and the objective of assessing  factors (glycemia),  which may interfere with the prognostic role of lactate, a parameter highly utilized in clinical practice. An interpretation of the prognostic role of lactate which consider other factors than just the absolute value of this parameter may be of great help of emergency physicians and intensivists. Indeed, lactate, highly utilized for bedside testing, assists in complex decision regarding circulatory support. Increased lactate values are observed in clinical conditions characterized by a significant increased in oxygen demand and lactate are involved in the clinical decising process of early identification of patients with cryptic shock even in prehospital care.

The main finding of the present investigation is that point-of-care lactate exhibited a tighter-adjusted differentiation capacity in patients with normal glycemia and without diabetes mellitus background. The Authors hypothesized that lactate’s predictive competence is better in normoglycemic subjects because the energy requirements of these patients are covered by glucose without lactate necessity. In these conditions, elevated lactate levels could be associated with tissue hypoperfusion leading to shock. On the other hand, in presence of hypoglycemia and hyperglycemia, baseline lactate levels may be already altered by the mutual interaction of the glucose-lactate axis. In their prospective multicenter longitudinal study, the Authors did manage to reach their primary objective, that is to analyze the lactate-glucose pathway and its interactions and to fine-tune the predictive performance of prehospital lactate since they documented that prehospital lactate blood levels may be influenced by abrupt changes in blood glucose levels.

Marjanovica  et al [3] assessed whether high-flow nasal oxygen can improve clinical signs of acute respiratory failure in acute heart failure (AHF)  by  comparing the effect of high-flow oxygen (minimum 50l/min) with noninvasive ventilation (NIV) on respiratory rate in patients admitted to an emergency department (ED) for AHF-related acute respiratory failure. This is a multicenter, randomized pilot study in three French EDs. Inclusion criteria were: adult patients with acute respiratory failure due to suspected AHF were included. Key exclusion criteria were urgent need for intubation, Glasgow Coma Scale <13 points or hemodynamic instability. The primary outcome was change in respiratory rate within the first hour of treatment and was analyzed with a linear mixed model. In the three participating centers, 145 patients were eligible and 60 patients were included in the study [median age 86 (interquartile range (IQR), 90; 92) years]. There was a median respiratory rate of 30.5 (IQR, 28; 33) and 29.5 (IQR, 27; 35) breaths/min in the high-flow oxygen and NIV groups respectively, with a median change of −10 (IQR, −12; −8) with high-flow nasal oxygen and −7 (IQR, −11; −5) breaths/min with NIV [estimated difference −2.6 breaths/min (95% confidence interval (CI), −0.5–5.7), P = 0.052] at 60 min.

Noninvasive ventilation (NIV) is a first-line treatment for acute respiratory failure due to AHF [4]. By means of intrathoracic positive pressure, especially positive end-expiratory pressure (PEEP), NIV is known to facilitate left ventricular work by decreasing left ventricular afterload and decreases venous return and right ventricular preload [5], therefore reducing reduces the work of breathing and improves respiratory mechanics. . Intolerance to NIV due to discomfort has been reported in up to 40% of patients and lead to treatment failure. On the other hand, high flow nasal cannula is associated with good tolerance  in a patient who is able to speak, eat and drink. High-flow nasal oxygen is able to generate a low level of positive pressure leading to a PEEP effect with alveolar recruitment and a washout of anatomical dead space, thereby improving CO2 clearance, which helps to relieve inspiratory effort.

The rationale of the study by Marjanovica  et al [3] is that studies comparing high flow nasal oxygenation with NIV have reported conflicting results [6,7] .

In their pilot study, Marjanovica  et al [3] did not observe a statistically significant difference in changes in respiratory rate among patients with acute respiratory failure due to AHF and managed with high-flow oxygen or NIV. This may be related to the small number of patients included in the study may be underpowered to detect a significant difference between groups. The Authors hypothesized that identification of more severe AHF is not easy since r  rate as a primary outcome in their study is potentially biased because respiratory rates from the ED are notoriously inaccurate and could be influenced by muscular fatigue. In other words, a low respiratory rate might indicate in some cases a serious condition. According to their results, the Authors suggest that the comparison between NIV and high flow oxygenation in AHF should be performed according to disease severity.



  1. Verdonschot RJCG, Buissant des Amorie FI, KoopmanSSHA, Rietdijk WJR, Ko SY, Sharma URU, Schluep M, den Uil CA, dos Reis Miranda D, MandigersL. Eligibility of cardiac arrest patients for extracorporeal cardiopulmonary resuscitation and their clinical characteristics: a retrospective two-centre study. EJEM 2024 Apr 1;31(2):118-126.
  2. Usategui-Martin R, Zalama-Sánchez D, López-Izquierdo R, Delgado Benito JF, del Pozo Vegas C, Sanchez Soberon I, Martin-Conty J, Sanz-Garcia A, Martin-Rodriguez F. Prehospital lactate-glucose interaction in acute lifethreatening illnesses: metabolic response and short-term mortality EJEM 2024 Jun 1;31(3):173-180.
  3. Marjanovica N, Piton N, Lamarre J, Alleyrat C, Couvreur R, Guanezan J, Mimoz O Frat JP. High-flow nasal cannula oxygen versus noninvasive ventilation for the management of acute cardiogenic pulmonary edema: a randomized controlled pilot study EJEM Feb 16. doi: 10.1097/MEJ.0000000000001128
  4. Rochwerg B, Brochard L, Elliott MW, Hess D, Hill NS, Nava S, et al. Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure. Eur Respir J 2017; 50:1602426
  5. Lenique F, Habis M, Lofaso F, Dubois-Randé JL, Harf A, Brochard L. Ventilatory and hemodynamic effects of continuous positive airway pressure in left heart failure. Am J Respir Crit Care Med 1997; 155:500–505.
  6. Osman A, Via G, Sallehuddin RM, Ahmad AH, Fei SK, Azil A, et al. Helmet continuous positive airway pressure vs. high flow nasal cannula oxygen in acute cardiogenic pulmonary oedema: a randomized controlled trial. Eur Heart J Acute Cardiovasc Care 2021; 10:1103–1111.
  7. Haywood ST, Whittle JS, Volakis LI, Dungan G, Bublewicz M, Kearney J, et al. HVNI vs NIPPV in the treatment of acute decompensated heart failure: subgroup analysis of a multi-center trial in the ED. Am J Emerg Med 2019; 37:2084–2090