Extracorporeal cardiopulmonary resuscitation for hypothermic refractory cardiac arrests in urban areas with temperate climates.

BACKGROUND: Accidental hypothermia designates an unintentional drop in body temperature below 35 °C. There is a major risk of ventricular fibrillation below 28 °C and cardiac arrest is almost inevitable below 24 °C. In such cases, conventional cardiopulmonary resuscitation is often inefficient. In urban areas with temperate climates, characterized by mild year-round temperatures, the outcome of patients with refractory hypothermic out-of-hospital cardiac arrest (OHCA) treated with extracorporeal cardiopulmonary resuscitation (ECPR) remains uncertain. METHODS: We conducted a retrospective monocentric observational study involving patients admitted to a university hospital in Paris, France. We reviewed patients admitted between January 1, 2011 and April 30, 2022. The primary outcome was survival at 28 days with good neurological outcomes, defined as Cerebral Performance Category 1 or 2. We performed a subgroup analysis distinguishing hypothermic refractory OHCA as either asphyxic or non-asphyxic. RESULTS: A total of 36 patients were analysed, 15 of whom (42%) survived at 28 days, including 13 (36%) with good neurological outcomes. Within the asphyxic subgroup, only 1 (10%) patient survived at 28 days, with poor neurological outcomes. A low-flow time of less than 60 min was not significantly associated with good neurological outcomes (P = 0.25). Prehospital ECPR demonstrated no statistically significant difference in terms of survival with good neurological outcomes compared with inhospital ECPR (P = 0.55). Among patients treated with inhospital ECPR, the HOPE score predicted a 30% survival rate and the observed survival was 6/19 (32%). CONCLUSION: Hypothermic refractory OHCA occurred even in urban areas with temperate climates, and survival with good neurological outcomes at 28 days stood at 36% for all patients treated with ECPR. We found no survivors with good neurological outcomes at 28 days in submersed patients.

Kidneys recovered from brain dead cardiac arrest patients resuscitated with ECPR show similar one-year graft survival compared to other donors.

INTRODUCTION: Among patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) as a second line of treatment for refractory out-of-hospital cardiac arrest (OHCA), some may develop brain death and become eligible for organ donation. The objective of this study was to evaluate long-term outcomes of kidney grafts recovered from these patients. MATERIAL AND METHODS: We conducted a retrospective monocentric observational study between January 1, 2011, and December 31, 2017. We exclusively included patients eligible for planned donation after brainstem death and from whom at least one organ graft was retrieved and transplanted. We compared two groups of brain dead patients: those treated with ECPR for refractory OHCA (ECPR group) and a diverse group of patients who did not receive ECPR, from which only 5/23 (22%) had OHCA (control group). The primary outcome was one-year kidney graft survival. RESULTS: We included 45 patients, 23 in the control group and 22 in the ECPR group. Although patients in the ECPR group were younger and had a lower prevalence of chronic renal disease (p = 0.01), their kidney function was more severely impaired upon admission in the ICU. A total of 68 kidney grafts were retrieved, transplanted, and studied, 34 in each study group. There was no significant difference between the two groups in terms of one-year kidney graft survival (p = 0.52). CONCLUSION: Organ transplantation from patients treated with ECPR after refractory OHCA showed one-year kidney graft survival rates comparable to those of patients not treated with ECPR.

Coronary lesions in refractory out of hospital cardiac arrest (OHCA) treated by extra corporeal pulmonary resuscitation (ECPR).

PURPOSE: Extracorporeal cardiopulmonary resuscitation (ECPR) is a second line treatment for refractory cardiac arrest (R-OHCA). Timing of ECPR before performing coronary angiography (CAG) is still debated. The aim of the study was to describe the clinical and angiographic characteristics of the largest cohort of out-of-hospital cardiac arrest (OHCA) patients undergoing ECPR. METHODS: All refractory OHCA patients with ECPR managed by the prehospital mobile intensive care unit (MoICU of the SAMU) in Paris (France) were prospectively included from October 2014 to December 2016. RESULTS: Among 74 patients included over the period, 54 patients had coronary artery disease (CAD). There is a trend toward the CAD patients being older but it did not meet statistical significance (55.3 ±â€¯11.8 vs. 50.6 ±â€¯12.8, p = 0,14). Patients were more frequently men and smokers (p = 0.03 for both). The proportion of initial shockable rhythm tended to be higher in patients with CAD (71% vs. 55%). The rate of 1-, 2-, and 3-vessel disease were 43%, 35% and 22% respectively. The Syntax Score was 18 ±â€¯9 and the lesions in each epicardial vessel were mainly proximal. Percutaneous coronary intervention was performed ad hoc in 49 patients (91%). Complete revascularization was performed in 64%. Inhospital death was numerically lower (65% vs. 75%) in patients with CAD, especially in patients with initial shockable rhythm. CONCLUSION: In 74 refractory OHCA patients treated with ECPR implanted by a prehospital mobile intensive care unit, the rate of CAD was high (54/74) especially in patients with shockable rhythm. The majority of patients presented with double or triple vessel disease and proximal lesions. The severity and extension of CAD may explain the refractory nature of the cardiac arrest.

A Pre-Hospital Extracorporeal Cardio Pulmonary Resuscitation (ECPR) strategy for treatment of refractory out hospital cardiac arrest: An observational study and propensity analysis.

BACKGROUND: Out of hospital cardiac arrest (OHCA) mortality rates remain very high with poor neurological outcome in survivors. Extracorporeal cardiopulmonary resuscitation (ECPR) is one of the treatments of refractory OHCA. This study used data from the mobile intensive care unit (MOICU) as part of the emergency medical system of Paris, and included all consecutive patients treated with ECPR (including pre-hospital ECPR) from 2011 to 2015 for the treatment of refractory OHCA, comparing two historical ECPR management strategies. METHODS: We consecutively included refractory OHCA patients. In Period 1, ECPR was indicated in selected patients after 30min of advanced life support; in- or pre-hospital implementation depended on estimated transportation time and ECPR team availability. In Period 2, patient care relied on early ECPR initiation after 20min of resuscitation, stringent patient selection, epinephrine dose limitation and deployment of ECPR team with initial response team. Primary outcome was survival with good neurological function Cerebral Performance Category score (CPC score) 1 and 2 at ICU discharge or day 28. FINDINGS: A total of 156 patients were included. (114 in Period 1 and 42 in Period 2). Baseline characteristics were similar. Mean low-flow duration was shorter by 20min (p<0.001) in Period 2. Survival was significantly higher in Period 2: 29% vs 8% (P<0.001), as confirmed by the multivariate analysis and propensity score. When combining stringent patient selection with an aggressive strategy, the survival rate increased to 38%. Pre-hospital ECPR implementation in itself was not an independent predictor of improved survival, but it was part of the strategy in Period 2. INTERPRETATION: Our data suggest that ECPR in specific settings in the management of refractory OHCA is feasible and can lead to a significant increase in neurological intact survivors. These data, however, need to be confirmed by a large RCT.

Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial.

BACKGROUND: Generalised convulsive status epilepticus (GCSE) should be treated quickly. Benzodiazepines are the only drug treatment available so far that is effective before admission to hospital. We assessed whether addition of the antiepileptic drug levetiracetam to the benzodiazepine clonazepam would improve prehospital treatment of GCSE. METHODS: We did a prehospital, randomised, double-blind, phase 3, placebo-controlled, superiority trial to determine the efficacy of adding intravenous levetiracetam (2.5 g) to clonazepam (1 mg) in treatment of GCSE in 13 emergency medical service centres and 26 hospital departments in France. Randomisation was done at the Paris Descartes Clinical Research Unit with a list of random numbers generated by computer. Adults with convulsions lasting longer than 5 min were randomly assigned (1:1) by prehospital physicians to receive levetiracetam or placebo in combination with clonazepam. All physicians and paramedics were masked to group assignments. If the status epilepticus lasted beyond 5 min after drug injection, a second dose of 1 mg clonazepam was given. The primary outcome was cessation of convulsions within 15 min of drug injection. We analysed the modified intention-to-treat population that had received at least one injection of clonazepam and levetiracetam or placebo, excluding patients without valid consent and those randomised more than once. The trial is registered at EudraCT, number 2007-005782-35. FINDINGS: Between July 20, 2009, and Dec 15, 2012, 107 patients were randomly assigned to receive placebo and 96 were assigned to receive levetiracetam. The trial was discontinued on Dec 15, 2012 when interim analysis showed no evidence of a treatment difference, and 68 patients in each group were included in the modified intention-to-treat analysis. Convulsions stopped at 15 min of drug injection in 57 of 68 patients (84%) receiving clonazepam and placebo and in 50 of 68 patients (74%) receiving clonazepam and levetiracetam (percentage difference -10.3%, 95% CI -24.0 to 3.4). Three deaths, 19 of 47 (40 %) serious adverse events, and 90 of 197 (46%) non-serious events were reported in the levetiracetam group, and four deaths, 28 of 47 (60%) serious events, and 107 of 197 (54%) non-serious events were reported in the placebo group. INTERPRETATION: The addition of levetiracetam to clonazepam treatment presented no advantage over clonazepam treatment alone in the control of GCSE before admission to hospital. Future prehospital trials could assess the efficacy of clonazepam alone as a first-line treatment in status epilepticus and the efficacy of a second injection of clonazepam with another antiepileptic drug as second-line treatment. FUNDING: UCB Pharma.

Safety and feasibility of prehospital extra corporeal life support implementation by non-surgeons for out-of-hospital refractory cardiac arrest.

BACKGROUND: Extra corporeal life support (ECLS) has been recently introduced in the treatment of refractory cardiac arrest (CA). Several studies have assessed the use of ECLS in refractory CA once the patients reach hospital. The time between CA and the implementation of ECLS is a major prognostic factor for survival. The main predictive factor for survival is ECLS access time. Pre hospital ECLS implementation could reduce access time. We therefore decided to assess the feasibility and safety of prehospital ECLS implementation (PH-ECLS) in a pilot study. METHODS AND RESULTS: From January 2011 to January 2012, PH-ECLS implementation for refractory CA was performed in 7 patients by a PH-ECLS team including emergency and/or intensivist physicians and paramedics. Patients were included prospectively and consecutively if the following criteria were met: they had a witnessed CA; CPR was initiated within the first 5 min of CA and/or there were signs of life during CPR; an PH-ECLS team was available and absence of severe comorbidities. ECLS flow was established in all patients. ECLS was started 22 min (±6) after the incision, and 57 min (±21) after the onset of advanced cardiovascular life support (ACLS). In one patient, ECLS was stopped for 10 min due to an accidental decannulation. One patient survived without sequelae. Three patients developed brain death. CONCLUSIONS: This pilot study suggests that PH-ECLS performed by non-surgeons is safe and feasible. Further studies are needed to confirm the time saved by this strategy and its potential effect on survival.

A prehospital randomized trial in convulsive status epilepticus.

Therapeutic strategies for patients with generalized convulsive status epilepticus (GCSE) need to be improved. We present the design of an add-on, randomized, double-blind, placebo-controlled, phase III clinical trial, to compare the efficacy for GCSE of intravenous levetiracetam in association with clonazepam versus clonazepam alone. In the therapeutic arm, 1 mg clonazepam is injected together with 2500 mg levetiracetam over 5 min. In the control arm, 1 mg clonazepam is injected together with a placebo over 5 min. This ongoing study is managed by prehospital physicians within emergency mobile units (SAMU). Adult patients with GCSE lasting more than 5 minutes are included in the study. The primary outcome measure is the percentage of patients with cessation of convulsions within 15 minutes of the onset of initial injections. Emergency medical consent is obtained from family members. An informed consent for continued participation is also obtained from patients when they wake. The study is currently recruiting participants.

Comparison of intravenous and intraosseous access by pre-hospital medical emergency personnel with and without CBRN protective equipment.

INTRODUCTION: Rapid intravascular access is a prerequisite component of emergency care and resuscitation. Peripheral intravenous (IV) access is the first-choice for most of the medical or trauma patients, but may be delayed in emergency conditions because of various difficulties. Elsewhere, intraosseous (IO) access may now be easily performed with a new semi-automatic battery-powered IO-insertion device (EZ-IO. The aim of this study was to compare the overall time to establish IO infusion with the EZ-IO device and the equivalent time for peripheral IV infusion, performed by emergency personnel in standard (No-CBRN) and in chemical, biological, radiological, and nuclear (CBRN) protective equipment. METHODS: Nine nurses and 16 physicians randomly performed 4 procedures on a training manikin: IV and IO access under No-CBRN conditions and IV and IO under CBRN conditions. The time for each infusion attempt included all the steps essential for a simulated safe clinical use of infusion. RESULTS: Under No-CBRN conditions, the time to establish IO infusion was shorter than the equivalent IV time (50+/-9 vs 70+/-30s). Similarly, under CBRN conditions, the time for IO infusion was shorter than for IV infusion (65+/-17 vs 104+/-30s). The mean time saved by IO infusion over IV infusion was respectively 20+/-24s (P<0.001) and 39+/-20s (P<0.001) under No-CBRN and CBRN conditions. CONCLUSION: The time to establish IO infusion was significantly shorter than that for peripheral IV infusion, under both No-CBRN and CBRN conditions. Further clinical studies are required to confirm that IO access would effectively save time over IV access in real pre-hospital emergency settings.