A novel capnogram analysis to guide ventilation during cardiopulmonary resuscitation: clinical and experimental observations.

BACKGROUND: Cardiopulmonary resuscitation (CPR) decreases lung volume below the functional residual capacity and can generate intrathoracic airway closure. Conversely, large insufflations can induce thoracic distension and jeopardize circulation. The capnogram (CO2 signal) obtained during continuous chest compressions can reflect intrathoracic airway closure, and we hypothesized here that it can also indicate thoracic distension. OBJECTIVES: To test whether a specific capnogram may identify thoracic distension during CPR and to assess the impact of thoracic distension on gas exchange and hemodynamics. METHODS: (1) In out-of-hospital cardiac arrest patients, we identified on capnograms three patterns: intrathoracic airway closure, thoracic distension or regular pattern. An algorithm was designed to identify them automatically. (2) To link CO2 patterns with ventilation, we conducted three experiments: (i) reproducing the CO2 patterns in human cadavers, (ii) assessing the influence of tidal volume and respiratory mechanics on thoracic distension using a mechanical lung model and (iii) exploring the impact of thoracic distension patterns on different circulation parameters during CPR on a pig model. MEASUREMENTS AND MAIN RESULTS: (1) Clinical data: 202 capnograms were collected. Intrathoracic airway closure was present in 35%, thoracic distension in 22% and regular pattern in 43%. (2) Experiments: (i) Higher insufflated volumes reproduced thoracic distension CO2 patterns in 5 cadavers. (ii) In the mechanical lung model, thoracic distension patterns were associated with higher volumes and longer time constants. (iii) In six pigs during CPR with various tidal volumes, a CO2 pattern of thoracic distension, but not tidal volume per se, was associated with a significant decrease in blood pressure and cerebral perfusion. CONCLUSIONS: During CPR, capnograms reflecting intrathoracic airway closure, thoracic distension or regular pattern can be identified. In the animal experiment, a thoracic distension pattern on the capnogram is associated with a negative impact of ventilation on blood pressure and cerebral perfusion during CPR, not predicted by tidal volume per se.

Targeted high mean arterial pressure aggravates cerebral hemodynamics after extracorporeal resuscitation in swine.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest. However, the optimal target to reach for mean arterial pressure (MAP) remains to be determined. We hypothesized that MAP levels critically modify cerebral hemodynamics during E-CPR and tested two distinct targets (65-75 vs 80-90 mmHg) in a porcine model. METHODS: Pigs were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until return of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. The dose of epinephrine was set to reach a standard or a high MAP target level (65-75 vs 80-90 mmHg, respectively). Animals were followed during 120-min after ROSC. RESULTS: Six animals were included in both groups. During E-CPR, high MAP improved carotid blood flow as compared to standard MAP. After ROSC, this was conversely decreased in high versus standard MAP, while intra-cranial pressure was superior. The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, also demonstrated inverted patterns of alteration according to MAP levels during E-CPR and after ROSC. In standard-MAP, PRx was transiently positive during E-CPR before returning to negative values after ROSC, demonstrating a reversible alteration of cerebral autoregulation during E-CPR. In high-MAP, PRx was negative during E-CPR but became sustainably positive after ROSC, demonstrating a prolonged alteration in cerebral autoregulation after ROSC. It was associated with a significant decrease in cerebral oxygen consumption in high- versus standard-MAP after ROSC. CONCLUSIONS: During early E-CPR, MAP target above 80 mmHg is associated with higher carotid blood flow and improved cerebral autoregulation. This pattern is inverted after ROSC with a better hemodynamic status with standard versus high-MAP.

Impact of panelists' experience on script concordance test scores of medical students.

BACKGROUND: The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel. METHODS: In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots. RESULTS: A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students' SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p < 0.0001 if N = 20; 67.2 vs 70.1, p < 0.0001 if N = 15 and 67.7 vs 68.4, p < 0.0001 if N = 10) and with EP compared to NEP (65.4 vs 67.1, p < 0.0001 if N = 20; 66.0 vs 67.2, p < 0.0001 if N = 15 and 62.5 vs 67.7, p < 0.0001 if N = 10). Bland & Altman plots showed good concordances between students' SCT scores, whatever the experience level of the expert panel. CONCLUSIONS: Even though student SCT scores differed statistically according to the expert panels, these differences were rather weak. These results open the possibility of including less-experienced experts in panels for the evaluation of medical students.

Extracorporeal Cardiopulmonary Resuscitation (ECPR) in the Prehospital Setting: An Illustrative Case of ECPR Performed in the Louvre Museum.

INTRODUCTION: Extracorporeal Cardiopulmonary Resuscitation (ECPR) is now considered for the treatment of refractory cardiac arrest. CASE REPORT: In an urban city like Paris, extraction times of in-hospital ECPR can be long for patients presenting with refractory cardiac arrest. Using the medicalized prehospital system, we developed a possible early prehospital ECPR implementation. This case report is an example of ECPR prehospital implementation in the Louvre Museum. CONCLUSION: Patients eligible for ECPR must be selected according to strict criteria. Further research is necessary to compare prehospital and in-hospital implementation.

Emergency Care for Homeless Patients: A French Multicenter Cohort Study.

OBJECTIVES: To determine whether homeless patients experience suboptimal care in the emergency department (ED) by the provision of fewer health care resources. METHODS: We conducted a prospective multicenter cohort study in 30 EDs in France. During 72 hours in March 2015, all homeless patients that visited the participating EDs were included in the study. The primary health care service measure was the order by the physician of a diagnostic investigation or provision of a treatment in the ED. Secondary measures of health care services included ED waiting time, number and type of investigations per patient, treatment in the ED, and discharge disposition. RESULTS: A total of 254 homeless patients and 254 nonhomeless patients were included. After excluding homeless patients that attended the ED for the sole purpose of housing, we analyzed 214 homeless and 214 nonhomeless. We found no significant difference between the 2 groups in terms of health care resource consumption, and for our secondary endpoints. CONCLUSIONS: We did not find significant differences in the level of medical care delivered in French EDs to homeless patients compared with matched nonhomeless patients.

A Brief Period of Hypothermia Induced by Total Liquid Ventilation Decreases End-Organ Damage and Multiorgan Failure Induced by Aortic Cross-Clamping.

BACKGROUND: In animal models, whole-body cooling reduces end-organ injury after cardiac arrest and other hypoperfusion states. The benefits of cooling in humans, however, are uncertain, possibly because detrimental effects of prolonged cooling may offset any potential benefit. Total liquid ventilation (TLV) provides both ultrafast cooling and rewarming. In previous reports, ultrafast cooling with TLV potently reduced neurological injury after experimental cardiac arrest in animals. We hypothesized that a brief period of rapid cooling and rewarming via TLV could also mitigate multiorgan failure (MOF) after ischemia-reperfusion induced by aortic cross-clamping. METHODS: Anesthetized rabbits were submitted to 30 minutes of supraceliac aortic cross-clamping followed by 300 minutes of reperfusion. They were allocated either to a normothermic procedure with conventional ventilation (control group) or to hypothermic TLV (33°C) before, during, and after cross-clamping (pre-clamp, per-clamp, and post-clamp groups, respectively). In all TLV groups, hypothermia was maintained for 75 minutes and switched to a rewarming mode before resumption to conventional mechanical ventilation. End points included cardiovascular, renal, liver, and inflammatory parameters measured 300 minutes after reperfusion. RESULTS: In the normothermic (control) group, ischemia-reperfusion injury produced evidence of MOF including severe vasoplegia, low cardiac output, acute kidney injury, and liver failure. In the TLV group, we observed gradual improvements in cardiac output in post-clamp, per-clamp, and pre-clamp groups versus control (53 ± 8, 64 ± 12, and 90 ± 24 vs 36 ± 23 mL/min/kg after 300 minutes of reperfusion, respectively). Liver biomarker levels were also lower in pre-clamp and per-clamp groups versus control. However, acute kidney injury was prevented in pre-clamp, and to a limited extent in per-clamp groups, but not in the post-clamp group. For instance, creatinine clearance was 4.8 ± 3.1 and 0.5 ± 0.6 mL/kg/min at the end of the follow-up in pre-clamp versus control animals (P = .0004). Histological examinations of the heart, kidney, liver, and jejunum in TLV and control groups also demonstrated reduced injury with TLV. CONCLUSIONS: A brief period of ultrafast cooling with TLV followed by rapid rewarming attenuated biochemical and histological markers of MOF after aortic cross-clamping. Cardiovascular and liver dysfunctions were limited by a brief period of hypothermic TLV, even when started after reperfusion. Conversely, acute kidney injury was limited only when hypothermia was started before reperfusion. Further work is needed to determine the clinical significance of our results and to identify the optimal duration and timing of TLV-induced hypothermia for end-organ protection in hypoperfusion states.

[Evolution of the nurse's role in the management of a cardiac arrest]. / Évolution du rôle de l'infirmier dans la prise en charge de l'arrêt cardiaque.

In France, there are 40 000 sudden deaths each year and the cardiac arrest survival rate is less than 10%. The arrival of extracorporeal cardio pulmonary resuscitation (ECPR) offers hope in the event of refractory cardiac arrest in prehospital care. Extending ECPR programmes requires more scientific evidence, training and an evolution of the role of paramedics.

Novel gas mixture combined with an auto-transfusion tourniquet enhances cerebral O2 transport and hemodynamic indices in CPR swine. Part B - A pilot experimental study.

Objectives: The cognitive outcome of CPR is poor. This study aims to evaluate if enhancing blood flow to the brain and oxygen dissociation from the hemoglobin improve cerebral O2 transport during CPR in cardiac arrest swine. Methods: Standard swine-CPR model of induced VF and recovery was treated with an auto-transfusion tourniquet (A-TT®; HemaShock® (HS) Oneg HaKarmel Ltd. Israel) and ventilation with a novel mixture of 30% Oxygen, 5% CO2, and 65% Argon (COXAR™). Five swine received the study treatment and 5 controls standard therapy. Animals were anesthetized, ventilated, and instrumented for blood draws and pressure measurements. Five minutes of no-CPR arrest were followed by 10 min of mechanical CPR with and without COXAR-HS™ enhancement followed by defibrillation and 45 min post ROSC follow-up. Results: All 5 COXAR-HS™ animals were resuscitated successfully as opposed to 3 of the control animals. Systolic (p < 0.05), and diastolic (p < 0.01) blood pressures, and coronary (p < 0.001) and cerebral (p < 0.05) perfusion pressures were higher in the COXAR-HS™ group after ROSC, as well as cerebral flow and O2 provided to the brain (p < 0.05). Blood pressure maintenance after ROSC required much higher doses of norepinephrine in the 3 resuscitated control animals vs. the 5 COXAR-HS™ animals (p < 0.05). jugular vein PO2 and SO2 exceeded 50 mmHg and 50%, respectively with COXAR-HS™. Conclusions: In this pilot experimental study, COXAR-HS™ was associated with higher diastolic blood pressure and coronary perfusion pressure with lower need of vasopressors after ROSC without significant differences prior to ROSC. The higher PjvO2 and SjvO2 suggest enhanced O2 provision to the brain mitochondria, while limb compression by the HS counteracts the vasodilatory effect of the CO2. Further studies are needed to explore and validate the COXAR-HS™ effects on actual post-ROSC brain functionality.

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.

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.

Expert consensus on training and accreditation for extracorporeal cardiopulmonary resuscitation an international, multidisciplinary modified Delphi Study.

BACKGROUND: A multidisciplinary group of stakeholders were used to identify: (1) the core competencies of a training program required to perform in-hospital ECPR initiation (2) additional competencies required to perform pre-hospital ECPR initiation and; (3) the optimal training method and maintenance protocol for delivering an ECPR program. METHODS: A modified Delphi process was undertaken utilising two web based survey rounds and one virtual meeting. Experts rated the importance of different aspects of ECPR training, competency and governance on a 9-point Likert scale. A diverse, representative group was targeted. Consensus was achieved when greater than 70% respondents rated a domain as critical (> or = 7 on the 9 point Likert scale). RESULTS: 35 international ECPR experts from 9 countries formed the expert panel, with a median number of 14 years of ECMO practice (interquartile range 11-38). Participant response rates were 97% (survey round one), 63% (virtual meeting) and 100% (survey round two). After the second round of the survey, 47 consensus statements were formed outlining a core set of competencies required for ECPR provision. We identified key elements required to safely train and perform ECPR including skill pre-requisites, surrogate skill identification, the importance of competency-based assessment over volume of practice and competency requirements for successful ECPR practice and skill maintenance. CONCLUSIONS: We present a series of core competencies, training requirements and ongoing governance protocols to guide safe ECPR implementation. These findings can be used to develop training syllabus and guide minimum standards for competency as the growth of ECPR practitioners continues.

Population Pharmacokinetics of Amikacin in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support leads to complex pharmacokinetic alterations, whereas adequate drug dosing is paramount for efficacy and absence of toxicity in critically ill patients. Amikacin is a major antibiotic used in nosocomial sepsis, especially for these patients. We aimed to describe amikacin pharmacokinetics on V-A ECMO support and to determine relevant variables to improve its dosing. All critically ill patients requiring empirical antimicrobial therapy, including amikacin for nosocomial sepsis supported or not by V-A ECMO, were included in a prospective population pharmacokinetic study. This population pharmacokinetic analysis was built with a dedicated software, and Monte Carlo simulations were performed to identify doses achieving therapeutic plasma concentrations. Thirty-nine patients were included (control n = 15, V-A ECMO n = 24); 215 plasma assays were performed and used for the modeling process. Patients received 29 (24-33) and 32 (30-35) mg/kg of amikacin in control and ECMO groups, respectively. Data were best described by a two-compartment model with first-order elimination. Inter-individual variabilities were observed on clearance, central compartment volume (V1), and peripherical compartment volume (V2). Three significant covariates explained these variabilities: Kidney Disease Improving Global Outcomes (KDIGO) stage on amikacin clearance, total body weight on V1, and ECMO support on V2. Our simulations showed that the adequate dosage of amikacin was 40 mg/kg in KDIGO stage 0 patients, while 25 mg/kg in KDIGO stage 3 patients was relevant. V-A ECMO support had only a secondary impact on amikacin pharmacokinetics, as compared to acute kidney injury.

HEAD AND THORAX ELEVATION PREVENTS THE RISE OF INTRACRANIAL PRESSURE DURING EXTRACORPOREAL RESUSCITATION IN SWINE.

Aim: Head and thorax elevation during cardiopulmonary resuscitation improves cerebral hemodynamics and ultimate neurological outcome after cardiac arrest. Its effect during extracorporeal cardiopulmonary resuscitation (E-CPR) is unknown. We tested whether this procedure could improve hemodynamics in swine treated by E-CPR. Methods and Results: Pigs were anesthetized and submitted to 15 minutes of untreated ventricular fibrillation followed by E-CPR. Animals randomly remained in flat position (flat group) or underwent head and thorax elevation since E-CPR institution (head-up group). Electric shocks were delivered after 30 minutes until the return of spontaneous circulation (ROSC). They were followed during 120 minutes after ROSC. After 30 minutes of E-CPR, ROSC was achieved in all animals, with no difference regarding blood pressure, heart rate, and extracorporeal membrane of oxygenation flow among groups. The head-up group had an attenuated increase in ICP as compared with the flat group after cardiac arrest (13 ± 1 vs. 26 ± 2 mm Hg at the end of the follow-up, respectively). Cerebral perfusion pressure tended to be higher in the head-up versus flat group despite not achieving statistical difference (66 ± 1 vs 46 ± 1 mm Hg at the end of the follow-up). Carotid blood flow and cerebral oxygen saturation were not significantly different among groups. Conclusion: During E-CPR, head and thorax elevation prevents ICP increase. Whether it could improve the ultimate neurological outcome in this situation deserves further investigation.

ECPR2: Expert Consensus on PeRcutaneous Cannulation for Extracorporeal CardioPulmonary Resuscitation.

AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a promising resuscitation strategy for select patients suffering from refractory out-of-hospital cardiac arrest (OHCA), though limited data exist regarding the best practices for ECPR initiation after OHCA. METHODS: We utilized a modified Delphi process consisting of two survey rounds and a virtual consensus meeting to systematically identify detailed best practices for ECPR initiation following adult non-traumatic OHCA. A modified Delphi process builds content validity and is an accepted method to develop consensus by eliciting expert opinions through multiple rounds of questionnaires. Consensus was achieved when items reached a high level of agreement, defined as greater than 80% responses for a particular item rated a 4 or 5 on a 5-point Likert scale. RESULTS: Snowball sampling generated a panel of 14 content experts, composed of physicians from four continents and five primary specialties. Seven existing institutional protocols for ECPR cannulation following OHCA were identified and merged into a single comprehensive list of 207 items. The panel reached consensus on 101 items meeting final criteria for inclusion: Prior to Patient Arrival (13 items), Inclusion Criteria (8), Exclusion Criteria (7), Patient Arrival (8), ECPR Cannulation (21), Go On Pump (18), and Post-Cannulation (26). CONCLUSION: We present a list of items for ECPR initiation following adult nontraumatic OHCA, generated using a modified Delphi process from an international panel of content experts. These findings may benefit centers currently performing ECPR in quality assurance and serve as a template for new ECPR programs.

Resuscitative endovascular balloon occlusion of the aorta vs epinephrine in the treatment of non-traumatic cardiac arrest in swine.

BACKGROUND: The administration of epinephrine in the management of non-traumatic cardiac arrest remains recommended despite controversial effects on neurologic outcome. The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) could be an interesting alternative. The aim of this study was to compare the effects of these 2 strategies on return of spontaneous circulation (ROSC) and cerebral hemodynamics during cardiopulmonary resuscitation (CPR) in a swine model of non-traumatic cardiac arrest. RESULTS: Anesthetized pigs were instrumented and submitted to ventricular fibrillation. After 4 min of no-flow and 18 min of basic life support (BLS) using a mechanical CPR device, animals were randomly submitted to either REBOA or epinephrine administration before defibrillation attempts. Six animals were included in each experimental group (Epinephrine or REBOA). Hemodynamic parameters were similar in both groups during BLS, i.e., before randomization. After epinephrine administration or REBOA, mean arterial pressure, coronary and cerebral perfusion pressures similarly increased in both groups. However, carotid blood flow (CBF) and cerebral regional oxygenation saturation were significantly higher with REBOA as compared to epinephrine administration (+ 125% and + 40%, respectively). ROSC was obtained in 5 animals in both groups. After resuscitation, CBF remained lower in the epinephrine group as compared to REBOA, but it did not achieve statistical significance. CONCLUSIONS: During CPR, REBOA is as efficient as epinephrine to facilitate ROSC. Unlike epinephrine, REBOA transitorily increases cerebral blood flow and could avoid its cerebral detrimental effects during CPR. These experimental findings suggest that the use of REBOA could be beneficial in the treatment of non-traumatic cardiac arrest.