# Evaluation of ventilatory parameters reporting in large animal models of cardiac arrest: a scoping review

Jean-Claude Li, Nicolas Segond, Arnaud Lesimple, Alice Hutin, Rebecca Goutchtat, Iann Drennan, Giuseppe Ristagno, Guillaume Debaty, Alain Cariou, Renaud Tissier, et al.

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## To cite this version:

Jean-Claude Li, Nicolas Segond, Arnaud Lesimple, Alice Hutin, Rebecca Goutchtat, et al. Evaluation of ventilatory parameters reporting in large animal models of cardiac arrest: a scoping review. Resuscitation Plus, 2025, pp.101185. 10.1016/j.resplu.2025.101185. hal-05406134

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Evaluation of ventilatory parameters reporting

in large animal models of cardiac arrest: a scoping review.

Jean-Claude Li<sup>1,2,3</sup>, Nicolas Segond<sup>4,5</sup>, Arnaud Lesimple<sup>6,7</sup>, Alice Hutin<sup>8</sup>, Rebecca Goutchtat

1,2, Iann Drennan<sup>9</sup>, Giuseppe Ristagno<sup>10,11</sup>, Guillaume Debaty<sup>4,5</sup>, Alain Cariou<sup>3</sup>,

Renaud Tissier<sup>1,2</sup> *†, Jean-Christophe Richard<sup>6,7</sup> *

1 Ecole nationale vétérinaire d'Alfort, IMRB, AfterROSC Network, 94700, Maisons-Alfort, France.

2 University Paris Est Créteil, INSERM, IMRB, F-94010, Créteil, France.

3 Medical ICU, Cochin Hospital, AP-HP Centre Université Paris Cité, AfterROSC Network, Paris, France.

4 Emergency Department and Mobile Intensive Care Unit, University Hospital of Grenoble Alpes, Grenoble, France

5 Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France

6 Vent'Lab, Medical Intensive Care Unit, Angers University Hospital, Angers, France

7 Med<sub>2</sub>Lab laboratory, Air Liquide Medical Systems, Antony, France

8 SAMU of Paris and intensive care unit, Necker University Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Paris 75015, France

9 Department of Family and Community Medicine, Division of Emergency Medicine, University of Toronto, Toronto, Ontario, Canada

10 Department of Pathophysiology and Transplantation, University of Milan, Italy

11 Department of Anesthesiology, Intensive Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

**World count** (excluding title page, abstract, references, tables and figures): **2753**.

\*, both authors contributed equally to this work

**Corresponding author:** Renaud Tissier

Ecole Nationale Vétérinaire d'Alfort

7 avenue du Général de Gaulle

94700 Maisons-Alfort, France

Tel: +33143967302; Email: renaud.tissier@vet-alfort.fr.

ORCID: 0000-0001-6602-939X
35 **Abstract**

36 **Background:** Ventilation is a critical determinant of cardiopulmonary resuscitation efficiency.

37 Our goal was to evaluate how ventilatory parameters are reported during cardiopulmonary
38 resuscitation in large animal models of cardiac arrest.

39 **Methods:** A scoping review was conducted following the PRISMA-ScR guidelines, including
40 studies referenced in Pubmed over the last decade (January 1st, 2015, to July 30th, 2025).

41 The review followed the PCC approach: (P) population: large animal models of cardiac arrest;
42 (C) concept: ventilatory settings and parameters during CPR; (C) context: studies aiming at
43 describing or evaluating mechanical or manual ventilation during CPR in experimental
44 conditions. The reporting of the animal characteristics, ventilatory settings and monitored
45 parameters were extracted and analyzed descriptively.

46 **Results:** We identified 111 relevant publications. Most of them used porcine models (79%),
47 with ventricular fibrillation being the most common method of cardiac arrest induction
48 (59%). Mechanical ventilation was predominant (75%), with volume and pressure-controlled
49 modes nearly equally represented. The reporting of critical ventilatory settings was
50 inconsistent, with a percentage of appropriate reporting as follows: respiratory rate (88%),
51 fraction of inspired oxygen (83%), positive end-expiratory pressure (49%), tidal volume (83%,
52 among studies with volume-controlled ventilation), peak inspiratory pressure (92%, among
53 studies with pressure-controlled ventilation) and inspiratory to expiratory ratio (17%, among
54 all studies with mechanical ventilation). Reporting of measured ventilatory parameters
55 during CPR was also limited with, e.g., EtCO₂ reported in 41% of the studies and arterial
56 blood gases sampled and reported in 50% of the studies.
57 **Conclusions:** This scoping review evidenced substantial variability and frequent omissions in the reporting of ventilatory settings and monitoring in large animal CPR studies. Updated recommendations could be useful to provide specific guidelines of reporting in the field.

60 **KEYWORDS:** Cardiac arrest; cardiopulmonary resuscitation; ventilation; ventilator; tidal volume; animal models; manual ventilation

63 **Acknowledgements**

64 The authors are grateful for the faculty members of the 1st, 2nd, and 3rd editions of the
65 Annecy's Round Table on Cardiopulmonary Resuscitation for the insightful discussions on this
66 topic, which indirectly contributed to the present work.

67
68 **Introduction**

69
In the field of resuscitation research, large animal models are essential for the
70
translation of experimental findings to clinical practice. In particular, pigs closely mimic
71
human cardiovascular and pulmonary physiology [1,2], allowing for realistic modeling of
72
ventilatory and hemodynamic interactions during cardiopulmonary resuscitation (CPR).
73
Beyond chest compression, which has been extensively investigated over the last decades,
74
the impact of ventilation during CPR is critical, but still insufficiently studied. For instance,
75
many ventilatory parameters such as tidal volume (Vt) or positive end-expiratory pressure
76
(PEEP) are known to influence intrathoracic pressure, coronary perfusion pressure and the
77
likelihood of return of spontaneous circulation (ROSC)[3-6]. When insufficient, ventilation
78
may impair gas exchange and limit oxygenation, while excessive ventilation could
79
compromise circulation by increasing lung volume above functional residual capacity (FRC)
80
and negatively impact venous return [7]. In addition, the continuous monitoring of
81
ventilatory parameters can provide surrogate markers of perfusion and ventilation quality
during CPR with e.g., end-tidal CO2 (EtCO2) or full capnogram analysis [8,9]. Accordingly,
82
rigorous reporting of experimental protocols and ventilatory parameters is essential in CPR
83
animal studies to ensure reproducibility and translational relevance in preclinical research.
84

85
In line with these requirements, the ARRIVE 2.0 guidelines, updated in 2020, offered a
86
structured checklist for the general report of animal studies [10]. However, these guidelines
87
only established general standards. More specifically, the Utstein-Style guidelines published
88
in 1996 [11] proposed a first template to harmonize resuscitation data reporting, including
89
ventilatory support, for laboratory CPR research. It remains unclear whether these
90
recommendations have effectively improved consistency across experimental studies,
particularly in light of the recent progress in ventilation and monitoring strategies during

CPR.

Accordingly, this scoping review aimed at systematically evaluating how ventilatory

parameters were reported in large-animal CPR studies over the last decade. Our literature

search strategy focused on studies properly describing and evaluating ventilation during CPR.

The goal is to pave the way for up-to-date future recommendations regarding ventilatory

monitoring and reporting in large animals CPR studies.

98
## 99 Methods

### 100 *Design*

101 This scoping review was drafted following the requirements of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Review (PRISMA-ScR).

### 104 *Eligibility criteria*

105 This scoping review included studies which matched the following PCC approach: (P)
106 population: defined as large animal models of cardiac arrest; (C) concept: defined as
107 ventilatory settings and monitored parameters during CPR; (C) context: experimental
108 laboratory studies on large animals, describing mechanical or manual ventilation under
109 controlled CPR conditions. The search was restricted to English publications. The following
110 types of publication were excluded: case reports, reviews, letters, commentaries, editorials,
111 comments. Animal models including the use of extracorporeal circulation were also
112 excluded.

### 113 *Information source*

114 Considering that ventilatory management during CPR is constantly evolving both in
115 clinical and preclinical studies, the search was restricted to the past ten years to ensure that
116 the included studies reflect current animal experimental practices. The bibliographic
117 database PubMed was searched for articles published from January 1st, 2015, to July 30th,
118 2025.

### 119 *Search strategy and selection process*

120 The search strategy was developed and refined through team discussions. It
121 contained keywords relevant to ventilation during cardiopulmonary resuscitation in large
122 animal models of cardiac arrest. The full literature search strategy is provided in
123 Supplemental material.

124 Articles were initially screened based on their titles and abstracts. Following the initial
125 screening, relevant full-text articles identified were reviewed. Any doubt regarding the
126 inclusion or exclusion of an article was resolved by discussion with a second independent
127 reviewer.

128 *Data charting and collection*

129 A data-charting form was developed by team discussion to determine which variables
130 to extract. Two reviewers discussed the results and updated the data-charting form in an
131 iterative process. Data extracted from the selected papers were classified into 3 categories:
132 1) Characteristics of animal models of CPR during cardiac arrest, 2) Ventilatory settings
133 during CPR 3) Ventilatory parameters monitored and reported during CPR.

134 Animal model characteristics included: the total number of animals, body weight, sex,
135 method of cardiac arrest induction, and the modality and rate of chest compressions.

136 Ventilatory settings reported during CPR included: ventilation interface and modality
137 (mechanical or manual), mode of ventilation when mechanical, ventilatory settings such as
138 respiratory rate, fraction of inspired oxygen (FiO₂) or oxygen flow (for mechanical and manual
139 ventilation respectively), tidal volume (Vt) and PEEP. Settings specific to mechanical
140 ventilation including inspiratory trigger, inspiratory to expiratory ratio (I:E), and peak
141 pressure alarm, as well as settings specific to manual ventilation including pressure-release
142 valve and bag volume were also investigated.

143 Ventilatory parameters monitored during CPR included: Vt, ventilation induced by
144 chest compressions called passive ventilation (figure 1), minute volume, peak inspiratory
145 pressure, intrathoracic pressure, and gas exchange variables such as peripheral oxygen
saturation ($SpO_2$), end-tidal carbon dioxide ($EtCO_2$) with or without volumetric analysis, and
arterial blood gases. Figure 1 also schematically illustrates airway pressures and full
capnogram during CPR.

Data synthesis and analysis

Variables were presented as numbers and percentages of publications evaluating or
reporting each condition or parameter. Numerical values of set parameters during CPR were
expressed as median and interquartile range. Statistical analyses were performed with
Microsoft Excel Software©.
154 **Results**

155 *Study selection*

156 A total of 200 studies were identified from PubMed. After excluding one corrigendum 157 counted as a duplicate, 199 studies were screened by title and abstract. Out of these, 126 158 studies passed the first screening and had full-text articles retrieved. Following secondary 159 screening, 15 were excluded because the experimental configuration was not considered 160 clinically relevant to ventilation monitoring. The remaining 111 studies were included in the 161 final analysis. The agreement between reviewers during the screening process was assessed 162 to ensure consistency in study selection, resulting in a Cohen's kappa coefficient of 0.8, 163 indicating excellent agreement. Figure 2 shows the PRISMA flow diagram for study inclusion 164 and exclusion. 165

165 *Animal characteristics*

166 As shown in Table 1, the vast majority of studies employed a porcine model (79%), 167 and the remainder used lamb (16%), or canine (5%) models. The median number of animals 168 per study was 22 (IQR 13-32). Median body weight was 32 kg (IQR 12-39) in pigs, 4 kg (IQR 4- 169 5) in lambs and 25 kg (IQR 13-27) in dogs. Lamb studies mostly focused on pediatric 170 conditions (4-5 kg). They were included in the full analysis as complying in the initial search 171 strategy. When reported, sex distribution was relatively balanced, with 21% males, 19% 172 females, and 36% including both sexes. 173

173 In most studies, cardiac arrest was induced by ventricular fibrillation with electrical 174 stimulation (59%). Asphyxia, achieved by occluding the endotracheal tube and disconnecting 175 the ventilator, constituted the second most frequent method (39%). 176

176 The majority of studies used chest compressions with an automated mechanical 177 device (52%). When manual chest compressions were applied (35%), compression quality
178 was monitored in 21% of the studies. Continuous chest compressions were more frequently
179 reported (68%) than interrupted compressions (35%), considering that few studies compared
180 both conditions and were included in both categories.

181 Ventilatory settings during cardiopulmonary resuscitation

182 As shown in Table 2, almost all studies relied on invasive ventilation (95%), most
183 frequently with mechanical ventilation (75%), while manual bag-valve ventilation was
184 reported in 26% of the studies. Continuous-flow oxygen was rarely used (6%).

185 Among mechanical ventilation strategies, volume-controlled (48%) and pressure-
186 controlled (46%) modes were nearly equally represented. Among the studies with volume or
187 pressure-controlled ventilation, a small proportion of studies reported specific CPR-adapted
188 modes (11%), including ultra-low tidal volume ventilation (ULTVV, 5%), chest compression
189 synchronized ventilation (CCSV, 4%), or cardiopulmonary ventilation (CPV, 1%).

190 Among ventilatory settings, the most frequently documented parameters were
191 respiratory rate (88%), Vt (83% among studies with ventilation controlled-ventilation),
192 inspiratory pressure (92%, among studies with pressure controlled-ventilation), FiO₂ or
193 oxygen flow (83%), and PEEP (49%). In contrast, only few studies reported the settings
194 (specific to mechanical ventilation) for inspiratory to expiratory ratio (17%), inspiratory
195 trigger (6%), or inspiratory pressure alarm (6%). Numerical values of the corresponding set
196 parameters are shown in Table 3.

197 Reporting of ventilatory parameters during cardiopulmonary resuscitation (CPR)

198 Table 4 shows the reporting of the different ventilatory parameters monitored during
199 CPR and reported in the included studies. Among all studies, only 23% reported Vt, 22%
200 documented peak inspiratory pressure, and 11% minute volume. Additionally, passive
201 ventilation (3%) and intrathoracic pressure (3%) were rarely measured.
202 EtCO₂ monitoring during CPR was described in 41% of the studies. Only 26% specified the sensor type (mainstream or sidestream), and 16% reported the use of volumetric capnography. Arterial blood gases were sampled during CPR in 50% of the studies. Of note, 12 studies mentioned EtCO₂ monitoring during CPR without reporting the corresponding data, 9 studies monitored peak inspiratory pressure but did not report it, and 4 studies monitored Vt and minute ventilation without providing the associated values.

208 Evaluation of arterial and/or tissular oxygenation was rare as only 14% of the studies reported arterial oxygen saturation (SaO₂), 13% reported mixed venous oxygen saturation (SvO₂) or mixed venous oxygen pressure (PvO₂) as indicators of tissue oxygen consumption, and 23% reported regional cerebral oxygenation with the use of near infrared spectroscopy or direct intraparenchymal probe.

213

214

215
216 **Discussion**

217 In this scoping review, we provided a comprehensive overview of ventilatory
218 parameters reporting in large animal models of CPR over the past decade, thirty years after
219 the establishment of the Utstein-Style Guidelines [11]. To our knowledge, this is the first
220 review to systematically describe ventilatory settings and monitoring practices during
221 experimental CPR.

222 Our analysis yielded several key observations. First, our findings are consistent with
223 previous reports highlighting variability in ventilatory strategies during both clinical and
224 experimental CPR [12]. Indeed, ventilatory strategies and settings were highly heterogenous
225 across studies. Most of the basic data recommended by the Utstein-Style Guidelines were
226 correctly reported: ventilatory interface (100%), ventilation mode when mechanical (88%),
227 inspired O₂ concentration or oxygen flow (83%), Vt set (83%), respiratory rate (88%),
228 synchronization with chest compressions (91%). The description of the PEEP level (49%) and
229 the inspiration to expiration ratio when mechanical (17%) were frequently neglected. Finally,
230 specific ventilator settings of inspiratory trigger and peak inspiratory pressure alarm were
231 almost never documented. In addition, monitoring of many variables were often absent,
232 such as Vt during CPR (23%), minute volume (11%) or peak inspiratory pressure (22%). In
233 fact, each of these parameters has the potential to significantly influence delivered
234 ventilation that may impact intrathoracic pressure, hemodynamics, and ultimately the
235 general outcome of most studies. Second, despite clinical findings and Utstein-Style
236 guidelines emphasizing the importance of monitoring EtCO₂ and blood gases as surrogates
237 for perfusion and ventilation quality [11,13], these variables were underreported in our
238 review. EtCO₂ during CPR was described in less than half of the studies, and when available,
239 waveform analysis or volumetric capnography was rarely included despite their potential
240 additional value [14,15]. Similarly, few studies documented intrathoracic pressure, even though it is highly relevant for assessing interactions between ventilation and chest compressions during CPR [16].

243 This lack of standardization has significant implications. Incomplete or heterogeneous reporting limits comparison across studies, reduces reproducibility, and hinders the interpretation of experimental findings. Furthermore, given the increasing reliance on animal models to guide clinical practice, harmonized reporting of ventilatory settings and monitoring during CPR is essential, along with the consistent use of a common terminology as previously suggested [17].

249 For instance, even if the settings for Vt were among the most widely reported in our analysis, the monitoring of the actual measured inspiratory and expiratory Vt was very rare. 250 Moreover, no methodological recommendations currently exist regarding its measurement. 251 The optimal Vt to be delivered during CPR, i.e. active ventilation, remains debated. In the 252 clinical field, a recent post hoc analysis of a large randomized controlled trial even suggested 253 that ventilation, measured by thoracic impedance, is most of the time inadequate before 254 advanced airway placement, and likely associated with a worse prognosis [18]. Therefore, 255 measuring and reporting of Vt is essential. Interestingly, after intubation, inspiratory Vt (Vt 256 delivered during inspiration time) should be preferred, as expiratory Vt is affected by chest 257 compressions and their impact on absolute lung volume (Figure 1). Of note, monitoring Vt 258 (whether inspiratory or expiratory) during ventilation without a secured airway remains 259 highly challenging due to inspiratory and expiratory leaks at the mask interface [19,20]. 260 Ventilation that results from repeated chest compressions and decompressions during the 261 expiration time, usually called passive ventilation, may also contribute to overall gas 262 exchange. In the landmark study from Peter Safar, passive ventilation evaluated in humans 263
264 was highly variable with gas movements induced by chest compressions ranging from 0 ml to 265 more than 50 ml [21]. In addition, the recently described airway closure phenomenon has 266 been incriminated as limiting passive ventilation [22]. Interestingly, internal functioning of 267 different medical devices may significantly increase (e.g. active decompression) or stop 268 passive ventilation (e.g. impedance threshold device or PEEP valve), thus impacting gas 269 exchange and absolute lung volumes. For this purpose, the measurement of flow entering 270 into the thorax during decompression (i.e., expiratory reverse flow, also known as ventilation 271 volume during decompression) may be recommended as a surrogate of passive ventilation 272 (Figure 1).

273 Among the monitored parameters acting as possible surrogates of ventilation and 274 CPR efficiency, it was also surprising that EtCO₂ was not widely reported. Although EtCO₂ 275 monitoring is easily available in laboratory settings, its proper interpretation could remain 276 challenging. EtCO₂ variation could indeed reflect blood flow induced by chest compressions 277 but also changes of global ventilation. A previous work showed that rather than the EtCO₂ 278 value, the maximum value of exhaled CO₂ (CO₂ max) might be a closer surrogate of alveolar 279 CO₂, and should therefore be monitored (figure 1) [23]. Thus, caution is warranted when 280 interpreting CO₂ signal. More recently, specific CO₂ patterns have been described allowing to 281 recognize potentially harmful situations such as airway closure or thoracic distension; in 282 these cases, adapting ventilation settings may permit to optimize respiratory support [15]. 283 The analysis of the capnogram could be considered as an insightful parameter to report in 284 complement of EtCO₂ measurements (including sensor type).

285 Accordingly, as a minimal requirement, future studies should ensure consistent 286 reporting of the parameters recommended by the current Utstein-Style guidelines, including 287 animal characteristics (weight, sex, method of cardiac arrest induction), ventilatory interface
and mode (when mechanical ventilation), FiO₂ or oxygen flow, Vt, PEEP, respiratory rate, and I:E ratio. During CPR, peak inspiratory pressure, inspiratory Vt, real minute volume, EtCO₂ and blood gas sampling with arterial and mixed venous oxygen saturation should also be documented. Additionally, we believe that it is important to report indexed inspiratory Vt to body weight and inspiratory trigger setting for mechanical ventilation. As stated above, measurement of expiratory Vt (when airways are secured) should not be recommended as it is highly dependent upon ventilators or monitoring devices and largely heterogeneous due to the impact of chest compressions. We also encourage the documentation of intrathoracic pressure, which could provide relevant information to interpret the potential hemodynamic impact of ventilation. To support this purpose, we provided a structured template of key variables that appear important for standardized reporting in future experimental CPR protocols (Table 5). Of note, the direct assessment of the hemodynamic effects of ventilation during CPR (which is not within the scope of this work) also provide valuable insights (e.g., using coronary perfusion pressure and tissular oxygen delivery).

This scoping review has several limitations. First, our review was limited to English-language publications over the past 10 years. Second, the heterogeneity of protocols prevented quantitative synthesis and the reliability of our analysis depended on the extent of reporting provided in the included studies. Finally, our review was restricted to large animal models, which may limit generalizability to small species or clinical settings. Although large animal models provide valuable insights into ventilatory physiology during CPR, translating these findings to human clinical practice remains challenging. Despite their similarity to human cardiopulmonary physiology, differences in chest morphology and airway anatomy may influence effect of ventilation and its impact on gas exchange during resuscitation. Furthermore, controlled experimental settings only partially reflect the complexity of human
312 cardiac arrest, including comorbidities and resuscitation quality. Beyond these biological and
313 contextual differences, methodological heterogeneity in ventilatory management and
314 monitoring further limits comparability between studies. By mapping current experimental
315 practices, this scoping review highlights methodological gaps that, if properly considered,
316 could improve validity and better delimit the translational value of animal research in CPR.

317

318 **Conclusion**

319 Ventilatory settings and monitoring during experimental CPR in animals are reported
320 with considerable variability and frequent omissions. Critical parameters such as PEEP, I:E
321 ratio, inspiratory trigger (specific to mechanical ventilation), and EtCO2 analysis are often
322 absent, highlighting the need for standardized reporting. Updating the minimal reporting
323 standards would improve comparability, strengthen translational relevance, and guide the
324 design of future animal studies.
## DECLARATIONS

### Funding

The study was partly funded by the Agence Nationale pour la Recherche (Grant Areg-shock ANR-21-CE17-0011-03 and Grant CPR-CO2 ANR-25-CE19-4339-01).

### Credit authorship contribution statement

All authors have read the journal's authorship agreement and policy on disclosure of potential conflicts of interest. JCL, AL, JCR and RT conceived and supervised the scoping review. JCL, AL, JCR and RT drafted the manuscript, and all authors contributed substantially to its revision. All authors take responsibility for the paper as a whole and approved the final version of the manuscript.

### Ethics approval

This study did not properly involve the use of animals but only analyzed published investigations.

### Declaration of competing interest

RT is shareholder of a start-up company dedicated to total liquid ventilation, which is not in the scope of the present work (Orixha). AL is medical engineer in the Med2Lab funded by Air Liquide Medical Systems. JCR reports part time salary for research activities (Med2Lab) from Air Liquide Medical Systems.

### Funding

The authors have stated they have no financial relationships relevant to this article to disclose.

### Acknowledgement

JCL is grateful to the greater Paris university hospitals (AP-HP, Assistance Publique - Hôpitaux de Paris) for funding his master's degree, enabling him to carry out this work.
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411 clinical observations. J Appl Physiol (1985) 2016;120:196-203.
412 https://doi.org/10.1152/JAPPLPHYSIOL.00632.2015.

413 [23] Grieco DL, Brochard LJ, Drouet A, Telias I, Delisle S, Bronchti G, et al.
414 Intrathoracic Airway Closure Impacts CO2 Signal and Delivered Ventilation
during Cardiopulmonary Resuscitation. Am J Respir Crit Care Med
415
416 2019;199:728-37. https://doi.org/10.1164/RCCM.201806-1111OC.

417

418
Figure 1. Schematic representation of the waveforms for important ventilation parameters during cardiopulmonary resuscitation.

Paw, Airway pressure; Ti, inspiration time; Te, expiration time; Flow, airway flow; Vti, inspiratory tidal volume, corresponding to the usual Vt value (active ventilation); Vdecomp, passive ventilation during chest decompression; CO₂ max, maximal exhaled CO₂ during expiration; EtCO₂, end-tidal CO₂.

<figure><img src="image_3.png" /></figure>

425

426
<figure><img src="image_4.png" /><figcaption>427 **Figure 2.** Flow chart of study selection</figcaption></figure>

428
Table 1. Main characteristics of the animal models in the included studies. Data are expressed as mean and IQR or number of publications and percentage of total number for each species.

* For chest compressions (mechanical vs manual or continuous vs interrupted), percentage can be superior to 100% since some studies compared different conditions.

<table><thead><tr><th></th><th>Total<br>(N = 111)</th><th>Pig<br>(N = 88)</th><th>Lamb<br>(N = 18)</th><th>Dog<br>(N = 5)</th></tr></thead><tbody><tr><th>Number of animals</th><td>22 (13-32)</td><td>20 (12-32)</td><td>24 (18-33)</td><td>20 (12-24)</td></tr><tr><th>Weight (kg)</th><td>27 (5-36)</td><td>32 (12-39)</td><td>4 (4-5)</td><td>25 (13-27)</td></tr><tr><th>Sex</th><td></td><td></td><td></td><td></td></tr></tbody></table>
<table><tbody><tr><td>Male</td><td>23 (21%)</td><td>23 (26%)</td><td>0 (0%)</td><td>4 (80%)</td></tr><tr><td>Female</td><td>21 (19%)</td><td>17 (19%)</td><td>0 (0%)</td><td>1 (20%)</td></tr><tr><td>Both</td><td>40 (36%)</td><td>21 (24%)</td><td>18 (100%)</td><td>0 (0%)</td></tr><tr><td>Not reported</td><td>27 (24%)</td><td>27 (31%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td colspan="5"><strong>Cardiac arrest</strong></td></tr><tr><td>Ventricular fibrillation</td><td>66 (59%)</td><td>62 (70%)</td><td>0 (0%)</td><td>4 (80%)</td></tr><tr><td>Asphyxia</td><td>43 (39%)</td><td>24 (27%)</td><td>18 (100%)</td><td>1 (20%)</td></tr><tr><td>Other</td><td>2 (2%)</td><td>2 (2%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td colspan="5"><strong>Chest compressions modality *</strong></td></tr><tr><td>Mechanical</td><td>58 (52%)</td><td>57 (65%)</td><td>0 (0%)</td><td>1 (20%)</td></tr><tr><td>Manual</td><td>39 (35%)</td><td>30 (34%)</td><td>5 (28%)</td><td>4 (80%)</td></tr><tr><td>Quality monitoring</td><td>8/39 (21%)</td><td>8/30 (27%)</td><td>0/5 (0%)</td><td>0/4 (0%)</td></tr><tr><td>Not reported</td><td>17 (15%)</td><td>4 (5%)</td><td>13 (72%)</td><td>0 (0%)</td></tr><tr><td colspan="5"><strong>Chest compression *</strong></td></tr><tr><td>Continuous</td><td>75 (68%)</td><td>72 (82%)</td><td>3 (17%)</td><td>0 (0%)</td></tr><tr><td>Interrupted</td><td>39 (35%)</td><td>22 (25%)</td><td>14 (78%)</td><td>3 (60%)</td></tr><tr><td>Not reported</td><td>10 (9%)</td><td>7 (8%)</td><td>1 (6%)</td><td>2 (40%)</td></tr></tbody></table>

430

431
Table 2. Reporting of the ventilatory settings during cardiopulmonary resuscitation (CPR) in the included studies.

Data are expressed as number of publications using or reporting the corresponding setting or parameter, as well as percentage of publication number.

Vt, tidal volume; Ppeak, peak inspiratory pressure; CPV, cardiopulmonary ventilation; CCSV, chest compression synchronized ventilation; ULTVV, ultra-low tidal volume ventilation; PEEP, positive end-expiratory pressure; FiO₂, fraction of inspired oxygen.

* For ventilation modality and mode, percentage can be superior to 100% since some studies compared different conditions.

<table><thead><tr><th></th><th>Total<br>(N=111)</th><th>Pig<br>(N=88)</th><th>Lamb<br>(N=18)</th><th>Dog<br>(N=5)</th></tr></thead><tbody><tr><td><strong>Ventilation</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Invasive</td><td>106 (95%)</td><td>85 (97%)</td><td>18 (100%)</td><td>3 (60%)</td></tr><tr><td>Non-invasive</td><td>1 (1%)</td><td>1 (1%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Both</td><td>4 (4%)</td><td>2 (2%)</td><td>0 (0%)</td><td>2 (40%)</td></tr><tr><td><strong>Ventilation modality *</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Mechanical</td><td>83 (75%)</td><td>61 (69%)</td><td>18 (100%)</td><td>4 (80%)</td></tr><tr><td>Bag valve device</td><td>29 (26%)</td><td>27 (31%)</td><td>1 (6%)</td><td>1 (20%)</td></tr><tr><td>Continuous flow oxygen</td><td>7 (6%)</td><td>7 (8%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Not reported</td><td>3 (3%)</td><td>3 (3%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td><strong>Ventilation mode (when mechanical) *</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Volume-controlled</td><td>40/83 (48%)</td><td>39/61 (64%)</td><td>0/18 (0%)</td><td>1/4 (25%)</td></tr><tr><td>Report of Vt set point</td><td>33/40 (83%)</td><td>33/39 (85%)</td><td>-</td><td>0/1 (0%)</td></tr><tr><td>Report of Vt relatively to body weight</td><td>30/40 (75%)</td><td>30/39 (77%)</td><td>-</td><td>0/1 (0%)</td></tr><tr><td>Pressure-controlled</td><td>38/83 (46%)</td><td>20/61 (33%)</td><td>18/18 (100%)</td><td>0/4 (0%)</td></tr><tr><td>Report of inspiratory pressure set point</td><td>35/38 (92%)</td><td>18/20 (90%)</td><td>17/18 (94%)</td><td></td></tr><tr><td>Specific CPR mode (e.g., CPV, CCSV, ULTVV)</td><td>9/83 (11%)</td><td>9/61 (15%)</td><td>0/18 (0%)</td><td>0/4 (0%)</td></tr><tr><td>Not reported</td><td>11/83 (13%)</td><td>8/61 (13%)</td><td>0/18 (0%)</td><td>3/4 (75%)</td></tr><tr><td><strong>Report of other ventilation parameters</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Respiratory rate</td><td>98 (88%)</td><td>77 (88%)</td><td>18 (100%)</td><td>3 (60%)</td></tr><tr><td>FiO₂ or Oxygen flow</td><td>92 (83%)</td><td>70 (80%)</td><td>18 (100%)</td><td>4 (80%)</td></tr><tr><td>PEEP</td><td>54 (49%)</td><td>37 (42%)</td><td>17 (94%)</td><td>0 (0%)</td></tr><tr><td><strong>Among studies with mechanical ventilation</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Inspiratory trigger</td><td>5/83 (6%)</td><td>5/61 (8%)</td><td>0/18 (0%)</td><td>0/4 (0%)</td></tr><tr><td>I:E ratio</td><td>14/83 (17%)</td><td>12/61 (20%)</td><td>2/18 (11%)</td><td>0/4 (0%)</td></tr><tr><td>Pressure alarm</td><td>5/83 (6%)</td><td>5/61 (8%)</td><td>0/18 (0%)</td><td>0/4 (0%)</td></tr><tr><td><strong>Among studies with bag valve device</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Pressure release valve</td><td>3/29 (10%)</td><td>3/27 (11%)</td><td>0/1 (0%)</td><td>0/1 (0%)</td></tr><tr><td>Bag volume</td><td>1/29 (3%)</td><td>1/27 (4%)</td><td>0/1 (0%)</td><td>0/1 (0%)</td></tr></tbody></table>
<caption>Table 3. Numerical values of set parameters during cardiopulmonary resuscitation (CPR) in the included studies when corresponding values were available.</caption>

When different values were reported in the same study in different groups, each experimental group was counted independently. Data are expressed as median (IQR). FiO₂, fraction of inspired oxygen; PEEP, positive end-expiratory pressure; Vt, tidal volume
* We couldn't calculate the respiratory rate for three studies as they only reported the compression to ventilation ratio without reporting the compression rate. We also excluded studies with continuous insufflation.

† We excluded studies which reported oxygen flow and not fraction of inspired oxygen
‡ When tidal volume was not indexed to body weight, we reported it to mean weight of animals in the corresponding study

<table><thead><tr><th></th><th>Total</th><th>Pig</th><th>Lamb</th><th>Dog</th></tr></thead><tbody><tr><td>Respiratory rate<br>(/ per minute) *</td><td>10 (10-30)<br>N=93</td><td>10 (10-20)<br>N=73</td><td>40 (30-40)<br>N=17</td><td>7 (7-9)<br>N=3</td></tr><tr><td>FiO₂ (%) †</td><td>100 (100-100)<br>N=83</td><td>100 (100-100)<br>N=61</td><td>100 (21-100)<br>N=18</td><td>61 (21-100)<br>N=4</td></tr><tr><td>PEEP (cmH₂O)</td><td>5 (1-5)<br>N=54</td><td>5 (0-5)<br>N=37</td><td>5 (5-5)<br>N=17</td><td>N=0</td></tr><tr><td>I:E ratio</td><td>1:2 (1:1.4 - 1:2)<br>N=14</td><td>1:2 (1:1.3 - 1:2)<br>N=12</td><td>1:2 (1:2 - 1:2)<br>N=2</td><td>N=0</td></tr><tr><td>Pressure alarm<br>(cmH₂O)</td><td>60 (60-60)<br>N=5</td><td>60 (60-60)<br>N=5</td><td>N=0</td><td>N=0</td></tr><tr><td>Set Vt (mL/kg)<br>among studies<br>with volume-controlled<br>ventilation ‡</td><td>10 (7-10)<br>N=33</td><td>10 (7-10)<br>N=33</td><td>N=0</td><td>N=0</td></tr><tr><td>Targeted Vt mL/kg,<br>among studies<br>with bag-valve<br>device ‡</td><td>9 (8-10)<br>N=19</td><td>9 (8-10)<br>N=18</td><td>N=0</td><td>12 (12-12)<br>N=1</td></tr><tr><td>Inspiratory<br>pressure (cmH₂O)<br>among studies<br>with pressure-controlled<br>ventilation</td><td>30 (25-34)<br>N=35</td><td>25 (20-30)<br>N=18</td><td>33 (30-35)<br>N=17</td><td>N=0</td></tr></tbody></table>
<caption>Table 4. Reporting of monitored ventilatory parameters during cardiopulmonary resuscitation (CPR) in the included studies.</caption>

Importantly, measured parameters can differ from set parameters due to metrological and physiological reasons, emphasizing the importance of subsequent reporting (e.g., Vt during bag ventilation, etc).

Data are expressed as numbers of publication using or reporting the corresponding setting or parameter, as well as percentage of publication number.

Vt, tidal volume; Ppeak, peak inspiratory pressure; EtCO₂, end-tidal CO₂; SpO₂, peripheral capillary oxygen saturation; SaO₂, arterial oxygen saturation; SvO₂, mixed venous oxygen saturation; PvO₂, mixed venous oxygen pressure

<table><thead><tr><th></th><th>Total<br>(N=111)</th><th>Pig<br>(N=88)</th><th>Lamb<br>(N=18)</th><th>Dog<br>(N=5)</th></tr></thead><tbody><tr><td colspan="5"><strong>Evaluation and report of monitored ventilation parameters</strong></td></tr><tr><td>Vt</td><td>25 (23%)</td><td>21 (24%)</td><td>4 (22%)</td><td>0 (0%)</td></tr><tr><td>Inspiratory Vt</td><td>8/25 (32%)</td><td>8/21 (38%)</td><td>0/4 (0%)</td><td></td></tr><tr><td>Expiratory Vt</td><td>7/25 (28%)</td><td>7/21 (33%)</td><td>0/4 (0%)</td><td></td></tr><tr><td>Minute volume</td><td>12 (11%)</td><td>12 (14%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Passive ventilation</td><td>3 (3%)</td><td>3 (3%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Ppeak</td><td>24 (22%)</td><td>24 (27%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Intrathoracic pressure</td><td>3 (3%)</td><td>3 (3%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td colspan="5"><strong>Evaluation and report of gas exchange parameters (during CPR)</strong></td></tr><tr><td>EtCO₂</td><td>45 (41%)</td><td>44 (50%)</td><td>0 (0%)</td><td>1 (20%)</td></tr><tr><td>Volumetric<br>capnography</td><td>7/45 (16%)</td><td>7/44 (16%)</td><td>-</td><td>0/1 (0%)</td></tr><tr><td>Mainstream sensor</td><td>10/45 (22%)</td><td>10/44 (23%)</td><td>-</td><td>0/1 (0%)</td></tr><tr><td>Side stream sensor</td><td>2/45 (4%)</td><td>2/44 (5%)</td><td>-</td><td>0/1 (0%)</td></tr><tr><td>Not reported</td><td>29/45 (64%)</td><td>28/44 (64%)</td><td>-</td><td>1/1 (100%)</td></tr><tr><td>Blood gases (per CPR)</td><td>56 (50%)</td><td>42 (48%)</td><td>11 (61%)</td><td>3 (60%)</td></tr><tr><td colspan="5"><strong>Evaluation of arterial and tissue oxygenation (during CPR)</strong></td></tr><tr><td>SpO₂</td><td>4 (4%)</td><td>4 (5%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>SaO₂</td><td>15 (14%)</td><td>10 (11%)</td><td>4 (22%)</td><td>1 (20%)</td></tr><tr><td>SvO₂ or PvO₂</td><td>14 (13%)</td><td>12 (14%)</td><td>1 (6%)</td><td>1 (20%)</td></tr><tr><td>Regional cerebral<br>oxygenation</td><td>26 (23%)</td><td>22 (25%)</td><td>4 (22%)</td><td>0 (0%)</td></tr></tbody></table>
<caption>**Table 5.** Proposition of ventilation settings and parameters that should be reported and measured for a comprehensive description of ventilation impact in large animal models of cardiopulmonary resuscitation (CPR).</caption>

FiO₂, fraction of inspired oxygen; Vt, tidal volume; PEEP, positive end-expiratory pressure; Ppeak, peak inspiratory pressure; EtCO₂, end-tidal CO₂; SaO₂, arterial oxygen saturation; SvO₂, mixed venous oxygen saturation; PvO₂, mixed venous oxygen pressure

<table><thead><tr><th colspan="2">Ventilatory settings during CPR</th></tr></thead><tbody><tr><td>Interface</td><td>Invasive or non-invasive</td></tr><tr><td>Modality</td><td>Mechanical, bag valve device, continuous flow oxygen or other</td></tr><tr><td>Mode</td><td>Volume-controlled, pressure-controlled, or specific CPR mode</td></tr><tr><td>Ventilation parameters</td><td>Respiratory rate, FiO₂, Vt (reported to body weight), PEEP, inspiratory trigger, and I:E ratio</td></tr></tbody><thead><tr><th colspan="2">Ventilatory parameters monitored during CPR</th></tr></thead><tbody><tr><td>Ventilation monitoring</td><td>Inspired Vt (active ventilation), Ppeak, minute volume (including passive ventilation)<br/>Source of measurements (ventilator or laboratory recordings)<br/>N.B.: Ideally, intrathoracic pressure is relevant during mechanical ventilation, but its measurement during CPR is technically difficult because the dynamic and unstable conditions complicate accurate and reproducible assessment</td></tr><tr><td>Gas exchange parameters</td><td>Blood gases<br/>EtCO₂, sensor type and ideally volumetric or waveform analysis (e.g., CO₂ max)</td></tr><tr><td>Arterial and tissular oxygenation</td><td>SaO₂, SvO₂ and/or PvO₂<br/>Ideally, cerebral oximetry with near infrared spectroscopy or intraparenchymal probe</td></tr></tbody></table>
440 List of Supplemental Materials

441 Supplemental Method: Search strategy

442 Supplemental Material: List of the references analyzed in the scoping review