Supplemental digital content
Endotoxemia following out-of-hospital cardiac arrest is associated with severity and duration of post cardiac arrest shock
D Grimaldi , B Sauneuf, E Guivarch, S Ricome, G Geri, J Charpentier, B Zuber, F Dumas, C Spaulding, JP Mira, A Cariou
Supplemental method
Out-of-hospital patient’s management
In Paris, management of OHCA involves mobile emergency units and fire departments.
They cover a population of 5 million inhabitants during the day and 2.5 million at night.
On witnessed call and in suspected cases of sudden cardiac arrest, the closest emergency unit is dispatched on the scene. Out-of-hospital resuscitation is delivered by an
emergency team, which includes at least 1 trained physician in emergency medicine.
Patients in whom ROSC is achieved are then referred to a tertiary center with an
intensive care unit and coronary intervention facilities available 24 hours a day, 7 days a week. Patients in whom the resuscitation process fails are not transported to hospital and are certified dead on the field.
Management of OHCA patients after hospital admission
Since 2000, in the absence of obvious extra-cardiac etiology of OHCA, all patients had coronary angiogram with PCI if needed immediately after hospital arrival and before ICU admission (1). In this case, a dedicated team from the ICU moves to the catheter laboratory and begins the management of the patient during the angiographic procedure. A percutaneous coronary intervention (PCI) was attempted in case an acute coronary artery occlusion or a thrombotic lesion could be considered as the culprit lesion responsible for the cardiac arrest. When coronary angiography was not conclusive, brain and angio-thoracic CT scan were performed (2). Therapeutic hypothermia was initiated immediately at ICU admission using external cooling by forced cold air during the first 24 hours to obtain a target temperature between 32 and 34°C as recommended by international guidelines (3). Sedation protocol to induce and maintain hypothermia was a combination of midazolam, fentanyl and rocuronium.
Data collection
Patients’ data were prospectively collected according to Utstein recommendations (4).
Baseline characteristics, location of cardiac arrest, and initial cardiac rhythm were included in the database.(1) Using data from the emergency medical service, we collected the intervals between the collapse and basic life support (BLS) (“no flow”), and between BLS and ROSC (“low-flow”), and total initial epinephrine dose. Coronary
angiography data were prospectively entered into the database as previously reported (1).
Comorbidities were prospectively recorded based on patients’ past history and included diabetes, cardiomyopathy (either ischemic, valvular, hypertrophic, dilated or rythmic), chronic renal failure (baseline creatinine clearance < 30ml/min or chronic haemodialysis), chronic respiratory failure (documented obstructive or restrictive decrease of FEV1, long term oxygenotherapy), chronic liver disease (cirrhosis, viral hepatitis), chronic neurological
conditions (hemiplegia, paraplegia, parkinson disease…) and solid cancer.
Supplementary tables
Table S1: Main comorbidities of patients with post-CA shock according to endotoxemia level
Whole population
N= 60
Low Etx (<0.4 EA) N = 31
Intermediate Etx (0.4-0.59 EA)
N = 18
High Etx (≥ 0.6 EA) N = 11
P value
Cardiomyopathy N (%) 25 (41.7) 13 (41.9) 6 (33.3) 6 (54.5) 0.18
Chronic respiratory
failure N (%) 9 (15) 4 (12.9) 4 (22.2) 1 (9.1) 0.60
Cancer N (%) 6 (10) 4 (12.9) 1 (5.5) 1 (9.1) 0.71
Chronic liver disease N
(%) 9 (15) 5 (16.1) 3 (16.7) 1 (9.1) 0.88
Diabetes N (%) 12 (20) 4 (12.9) 5 (27.8) 3 (27.3) 0.29
Chronic neurological
disease N (%) 7 (11.7) 3 (9.7) 1 (5.5) 3 (27.3) 0.14
Chronic Renal Failure
N (%) 6 (10) 0 (0) 4 (22.2) 2 (18.2) 0.02
Table S2: Determinants of vasopressor free days using endotoxin as a continuous variable (crude and adjusted analysis)
Baseline characteristics
Crude Estimate (95% CI)
P value
Adjusted Estimate (95% CI)
P value Female gender -0.22 (-1.95 ; +1.50) 0.80
Age -0.016 (-0.07 ; +0.038) 0.56
Public place of cardiac
arrest +2.33 (0.82 ; 3.85) 0.003 1.61 (0.15 ; 3.07) 0.03
Witnessed -0.043 (-1.68 ; +1.59) 0.96
Non-shockable rhythm -0.86 (-2.46; +0.75) 0.29
Time to ROSC (min) -0.093 (-0.14 ; -0.045) <0.001 -0.08 (-0.13 ; -0.03) 0.001 Epinephrine dose (mg) -0.12 (-0.41 ; +0.16) 0.39
Etx (continuous variable) -3.29 (-6.37 ; -0.21) 0.04 -2.14 (-4.93 ; 0.65) 0.13
First, bivariate linear regression was performed to determine the variables associated with vasopressor free days. All variables associated with vasopressor free days with a p < 0.15 were included in the multivariate model. Multivariable linear regression was performed using backward selection.
Table S3: Determinants of mean daily vasopressor dose using endotoxin as a continuous variable (crude and adjusted analysis)
Baseline characteristics Crude estimate (95% CI)
P value
Adjusted Estimate (95% CI)
P value Female gender -46.2 (-107.8 ; +15.3) 0.138 31.1 (-86.6 ; +24.5) 0.27
Age -0.30 ( -2.27 ; +1.68) 0.76
Public Place of cardiac
arrest 26.8 (-19.9 ; +73.4) 0.22
Witnessed 14.4 (-46.23 ; +75.1) 0.64
Non-shockable rhythm 72.4 (16.6 ;128) 0.01 57.4 (4.63 - 110.2) 0.03 Time to ROSC (/min) 1.19 (-0.76 ; +3.14) 0.23
Epinephrine dose (/mg) 9.16 (-1.08 ; +19.4) 0.08 4.9 (-5.0 ; +14.8) 0.32
Etx (continuous variable) 216 (114.54 ; 317.5) <.001 163.6 (50.3 ; 276.9) 0.005
First, bivariate linear regression was performed to determine the variables associated with mean daily vasopressor dose. All variables associated with mean daily vasopressor dose with a p
< 0.15 were included in the multivariate model. Multivariable linear regression was performed using backward selection.
Supplementary figures
Supplementary fig 1. : Algorithm of haemodynamic treatment
TTE : TransThoracic echocardiography, CO : Cardiac Output, MAP : Mean arterial pressure
Supplementary fig. 2: Endotoxin level according to the presence of post-CA shock
Endotoxin level according to the presence of post-cardiac arrest shock in the 92 patients in whom endotoxin was measured. Data are shown as box plots. Comparison using Mann-Whitney test, p=0.002
Supplementary fig 3. : SOFA score according to endotoxemia level in all patients (with and without post-cardiac arrest shock)
Day 1 SOFA score across the endotoxin class at ICU admission in 92 patients was compared using Kruskall Wallis test.
Supplementary fig 4. : Kaplan Meier survival curves according to endotoxemia level class in all patients (with and without post-cardiac arrest shock)
Follow-up is in days; survival curves were compared using the log-rank test. Follow-up was 1263 patient-days.
Supplementary references
1. Dumas F, Cariou A, Manzo-Silberman S, et al. Immediate percutaneous coronary intervention is associated with better survival after out-of-hospital cardiac arrest:
insights from the PROCAT (Parisian Region Out of hospital Cardiac ArresT) registry. Circ Cardiovasc Interv 2010;3(3):200-207.
2. Chelly J, Mongardon N, Dumas F, et al. Benefit of an early and systematic imaging procedure after cardiac arrest: Insights from the PROCAT (Parisian Region Out of Hospital Cardiac Arrest) registry. Resuscitation 2012.
3. Nolan JP, Neumar RW, Adrie C, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the
International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the
Council on Clinical Cardiology; the Council on Stroke. Resuscitation 2008;79(3):350-379.
4. Jacobs I, Nadkarni V, Bahr J, et al. Cardiac arrest and cardiopulmonary
resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the international liaison committee on resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa). Resuscitation 2004;63(3):233-249.
5. Lemiale V, Dumas F, Mongardon N, et al. Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort.
Intensive Care Med 2013;39(11):1972-1980.
