Prehospital oxygen-therapy and mortality in patients treated by emergency medical services: a prospective, observational multicenter study

doi:10.5847/wjem.j.1920-8642.2025.084

Abstract

Abstract:

BACKGROUND: Oxygen supply is a common procedure performed by emergency medical services (EMS); however, whether prehospital oxygen or fraction of inspired oxygen (FiO₂) therapy predict mortality has not been studied to date. This study aims to determine mortality associated with oxygen therapy in unselected patients with acute disease who underwent prehospital care.

METHODS: This was a prospective, observational, cohort, multicenter, EMS-delivery, ambulance-based study. Adults with unselected acute disease who were managed by EMS and evacuated with high priority to the emergency department of four hospitals in three Spanish provinces. Epidemiological variables, on-scene vital signs, and prehospital blood analysis data were collected. The primary outcome was short- (2-, 7-, and 30-day), medium- (90- and 180-day), and long-term (365-day) all-cause cumulative mortality. The samples were a priori split according to thresholds of their received FiO₂(FiO₂=0.21, that is without oxygen therapy; FiO₂ between 0.22 and 0.49; and FiO₂≥0.5). The categorical variables FiO₂, epidemiological variables, vital signs, prehospital point-of-care testing (POCT) and patient outcomes were fitted with a logistic regression model. Additionally, a propensity score matching and a survival analysis were used.

RESULTS: The final sample included 7,494 patients, 70.3% of whom did not receive oxygen therapy, 15% with a FiO₂ between 0.22 and 0.49, and 14.7% with a FiO₂≥0.5. The 2-day mortality was 0.4%, 5.3%, and 22.9% respectively (P<0.001). The 365-day mortality was 9.9%, 33.1%, and 50.5% respectively (P<0.001). Finally, the FiO₂ predictive capacities 2-,30-, and 365-day mortality were AUC=0.870 (95%CI: 0.840-0.899), 0.810 (95%CI: 0.784-0.837), 0.704 (95%CI: 0.679-0.728), respectively.

CONCLUSION: Prehospital oxygen therapy by thresholds of FiO₂ was linked to death and allowed mortality prediction. This finding could provide an aid for EMS providers, allowing to assess more individualized patient risk.

Key words: Oxygen-therapy, Mortality, Prehospital, Fraction of inspired oxygen, Emergency medical services

Carlos del Pozo Vegas, Ancor Sanz-García, Antonio Dueñas-Ruiz, Pedro de Santos Castro, Ana Gil Contreras, María Blanco González, Alberto Correas Galán, Joan B. Soriano, Raúl López-Izquierdo, Francisco Martín-Rodríguez. Prehospital oxygen-therapy and mortality in patients treated by emergency medical services: a prospective, observational multicenter study[J]. World Journal of Emergency Medicine, 2025, 16(4): 357-366.

Figures/Tables 5

Figure 1.

Table 1.

Table 2.

Outcomes and other determinants based on prehospital oxygen therapy support FiO2 thresholds

Variables	FiO₂ thresholds			P-value
Variables	0.21 (n=5,267)	0.22-0.49 (n=1,123)	≥ 0.5 (n=1,104)	P-value
Prehospital oxygen-therapy support
None	5,267 (100)	0 (0)	0 (0)	<0.001
Nasal-cannula	0 (0)	589 (52.4)	0 (0)	<0.001
Nebulizer mask	0 (0)	404 (35.8)	301 (27.3)	<0.001
Venturi mask	0 (0)	342 (30.5)	285 (25.7)	<0.001
Nonrebreather mask	0 (0)	0 (0)	163 (14.8)	<0.001
NIMV	0 (0)	46 (4.1)	215 (19.5)	<0.001
IMV	0 (0)	8 (0.7)	439 (39.8)	<0.001
On-scene vital signs post administration of prehospital oxygen-therapy support
RR, breaths/min	16 (14-18)	19 (16-25)	18 (15-26)	<0.001
Saturation, %	98 (96-99)	97 (95-99)	97 (93-99)	<0.001
SBP, mmHg	133 (116-145)	130 (109-144)	125 (104-145)	<0.001
DBP, mmHg	72 (62-86)	69 (58-83)	69 (56-86)	<0.001
HR, beats/min	80 (70-94)	90 (76-104)	97 (80-113)	<0.001
Temperature, °C	36.1 (36-36.5)	36.4 (36-36.8)	36.1 (35.7-36.7)	<0.001
GCS, points	15 (15-15)	15 (15-15)	12 (3-15)	<0.001
Prehospital diagnosis
Cardiovascular	2,237 (42.5)	345 (30.7)	317 (28.7)	<0.001
Neurology	1,147 (21.8)	153 (13.6)	159 (14.4)
Trauma and injury	743 (14.1)	98 (8.7)	186 (16.8)
Respiratory	59 (1.1)	263 (23.4)	198 (17.9)
Poisoning	435 (8.3)	37 (3.3)	96 (8.7)
Infection	194 (3.7)	157 (14)	100 (9.1)
Digestive	272 (5.2)	27 (2.4)	17 (1.5)
Endocrine	101 (1.9)	22 (2.0)	19 (1.7)
Anaphylaxis	47 (0.9)	20 (1.8)	11 (1.0)
Others	32 (0.6)	1 (0.1)	1 (0.1)
Hospital outcomes
aCCI, points	4 (1-6)	6 (4-8)	5 (2-8)	<0.001
Hospital-admission	2,178 (41.4)	838 (74.6)	1,001 (90.7)	<0.001
Critical care unit-admission
Intensive care unit	201 (3.8)	126 (11.2)	502 (45.5)	<0.001
ACCU	428 (8.1)	93 (8.3)	95 (8.6)	0.868
Stroke care unit	366 (6.9)	32 (2.8)	11 (1)	<0.001
Cumulative mortality
2-day	23 (0.4)	60 (5.3)	253 (22.9)	<0.001
7-day	76 (1.4)	100 (8.9)	318 (28.8)	<0.001
30-day	160 (3.0)	180 (16.0)	404 (36.6)	<0.001
90-day	282 (5.4)	254 (22.6)	482 (43.7)	<0.001
180-day	371 (7.0)	309 (27.5)	525 (47.6)	<0.001
365-day	521 (9.9)	372 (33.1)	558 (50.5)	<0.001

Table 2.

Table 3.

Figure 2.

References 33

1	Mæhlen JO, Mikalsen R, Heimdal HJ, Rehn M, Hagemo JS, Ottestad W. Pre-hospital critical care management of severe hypoxemia in victims of Covid-19: a case series. Scand J Trauma Resusc Emerg Med. 2021; 29(1): 16.
2	Balen F, Lamy S, Fraisse S, Trinari J, Bounes V, Dubucs X, et al. Predictive factors for early requirement of respiratory support through phone call to Emergency Medical Call Centre for dyspnoea: a retrospective cohort study. Eur J Emerg Med. 2023; 30(6): 432-7. doi: 10.1097/MEJ.0000000000001066 pmid: 37556209
3	nada-Kim M, Chmiel FP, Boniface M, Burns D, Pocock H, Black J, et al. Validation of oxygen saturations measured in the community by emergency medical services as a marker of clinical deterioration in patients with confirmed COVID-19: a retrospective cohort study. BMJ Open. 2024; 14(1): e067378.
4	Kondo Y, Gibo K, Abe T, Fukuda T, Kukita I. Association of prehospital oxygen administration and mortality in severe trauma patients (PROMIS): a nationwide cohort study. Medicine (Baltimore). 2019; 98(27): e16307.
5	Chen PS, Chiu WT, Hsu PL, Lin SC, Peng IC, Wang CY, et al. Pathophysiological implications of hypoxia in human diseases. J Biomed Sci. 2020; 27(1): 63.
6	Swenson KE, Ruoss SJ, Swenson ER. The pathophysiology and dangers of silent hypoxemia in COVID-19 lung injury. Ann Am Thorac Soc. 2021; 18(7): 1098-105. doi: 10.1513/AnnalsATS.202011-1376CME pmid: 33621159
7	Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016; 316(15): 1583-9. doi: 10.1001/jama.2016.11993 pmid: 27706466
8	Hodroge SS, Glenn M, Breyre A, Lee B, Aldridge NR, Sporer KA, et al. Adult patients with respiratory distress: current evidence-based recommendations for prehospital care. West J Emerg Med. 2020; 21(4): 849-57. doi: 10.5811/westjem.2020.2.43896 pmid: 32726255
9	Smida T, Menegazzi JJ, Crowe RP, Bardes J, Scheidler JF, Salcido DD. Association of prehospital post-resuscitation peripheral oxygen saturation with survival following out-of-hospital cardiac arrest. Resuscitation. 2022; 181: 28-36. doi: 10.1016/j.resuscitation.2022.10.011 pmid: 36272616
10	Hayes-Bradley C, Miller M, Kua BH, Ragavan D, Gospel A, Partyka C, et al. Factors associated with desaturation in prehospital rapid sequence intubation in a helicopter emergency medical service. Air Med J. 2024; 43(2): 157-62. doi: 10.1016/j.amj.2023.11.013 pmid: 38490780
11	Klitgaard TL, Schjørring OL, Nielsen FM, Meyhoff CS, Perner A, Wetterslev J, et al. Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit. Cochrane Database Syst Rev. 2023; 9(9): CD012631.
12	Cao L, Chen Q, Xiang YY, Xiao C, Tan YT, Li H. Effects of oxygenation targets on mortality in critically ill patients in intensive care units: a systematic review and meta-analysis. Anesth Analg. 2024; 139(4): 734-42. doi: 10.1213/ANE.0000000000006859 pmid: 38315626
13	Echevarria C, Steer J, Bourke SC. Comparison of early warning scores in patients with COPD exacerbation: DECAF and NEWS score. Thorax. 2019; 74(10): 941-6. doi: 10.1136/thoraxjnl-2019-213470 pmid: 31387892
14	Bernard SA, Bray JE, Smith K, Stephenson M, Finn J, Grantham H, et al. Effect of lower vs higher oxygen saturation targets on survival to hospital discharge among patients resuscitated after out-of-hospital cardiac arrest: the EXACT randomized clinical trial. JAMA. 2022; 328(18): 1818-26. doi: 10.1001/jama.2022.17701 pmid: 36286192
15	Baekgaard J, Siersma V, Christensen RE, Ottosen CI, Gyldenkærne KB, Garoussian J, et al. A high fraction of inspired oxygen may increase mortality in intubated trauma patients - A retrospective cohort study. Injury. 2022; 53(1): 190-7.
16	Yusin G, Farley C, Dorris CS, Yusina S, Zaatari S, Goyal M. The effect of early severe hyperoxia in adults intubated in the prehosptial setting or emergency department: a scoping review. J Emerg Med. 2023; 65(6): e495-e510.
17	Dylla L, Adler DH, Abar B, Benesch C, Jones CMC, Kerry O’Banion M, et al. Prehospital supplemental oxygen for acute stroke - A retrospective analysis. Am J Emerg Med. 2020; 38(11): 2324-8. doi: 10.1016/j.ajem.2019.11.002 pmid: 31787444
18	Chen SM, Kuhn M, Prettner K, Yu FY, Yang T, Bärnighausen T, et al. The global economic burden of chronic obstructive pulmonary disease for 204 countries and territories in 2020-50: a health-augmented macroeconomic modelling study. Lancet Glob Health. 2023;11(8): e1183-e1193.
19	Ergan B, Nava S. Long-term oxygen therapy in COPD patients who do not meet the actual recommendations. COPD. 2017; 14(3): 351-66. doi: 10.1080/15412555.2017.1319918 pmid: 28506089
20	Pinto-Villalba RS, Leon-Rojas JE. Reported adverse events during out-of-hospital mechanical ventilation and ventilatory support in emergency medical services and critical care transport crews: a systematic review. Front Med (Lausanne). 2023; 10: 1229053.
21	Krieger JA, Sheehan J, Hernandez MA, Thau MR, Johnson NJ, Robinson BRH. Characteristics of victims of trauma requiring invasive mechanical ventilation with a short stay in critical care. Am J Emerg Med. 2024; 77: 1-6. doi: 10.1016/j.ajem.2023.11.054 pmid: 38096634
22	Schauer SG, April MD, Naylor JF, Mould-Millman NK, Bebarta VS, Becker TE, et al. Incidence of hyperoxia in combat wounded in Iraq and Afghanistan: a potential opportunity for oxygen conservation. Mil Med. 2019; 184(11-12): 661-7. doi: 10.1093/milmed/usz125 pmid: 31141134
23	Martín-Rodríguez F, López-Izquierdo R, Del Pozo Vegas C, Delgado-Benito JF, Ortega GJ, Castro Villamor MA, et al. Association of prehospital oxygen saturation to inspired oxygen ratio with 1-, 2-, and 7-day mortality. JAMA Netw Open. 2021; 4(4): e215700.
24	Lie SL, Hisdal J, Rehn M, Høiseth LØ. Hemodynamic effects of supplemental oxygen versus air in simulated blood loss in healthy volunteers: a randomized, controlled, double-blind, crossover trial. Intensive Care Med Exp. 2023; 11(1): 76.
25	Yarnell CJ, Angriman F, Ferreyro BL, Liu K, De Grooth HJ, Burry L, et al. Oxygenation thresholds for invasive ventilation in hypoxemic respiratory failure: a target trial emulation in two cohorts. Crit Care. 2023; 27(1): 67.
26	Yamamoto R, Fujishima S, Yamakawa K, Abe T, Ogura H, Saitoh D, et al. Hyperoxia for sepsis and development of acute lung injury with increased mortality. BMJ Open Respir Res. 2023; 10(1): e001968.
27	Castro Villamor MA, Alonso-Sanz M, López-Izquierdo R, Delgado Benito JF, Del Pozo Vegas C, López Torres S, et al. Comparison of eight prehospital early warning scores in life-threatening acute respiratory distress: a prospective, observational, multicentre, ambulance-based, external validation study. Lancet Digit Health. 2024; 6(3): e166-e175.
28	Heard AM, Lacquiere DA, Gordon HL, Douglas SG, Avis HJ. A case series of the Royal Perth Hospital Cannula-first approach in the 'can’t intubate, can’t oxygenate' scenario. Anaesth Intensive Care. 2024; 52(3): 159-67.
29	Wigginton O, Johnson S, Jervis B, Joshi A, Steere M, Ferguson I. Prehospital blood transfusion: a cross-sectional study of prehospital and retrieval medicine services across Australia & Aotearoa-New Zealand. Prehosp Emerg Care. 2024; 28(8): 1017-21.
30	Kruit N, Burrell A, Tian D, Barrett N, Bělohlávek J, Bernard S, et al. Expert consensus on training and accreditation for extracorporeal cardiopulmonary resuscitation an international, multidisciplinary modified Delphi Study. Resuscitation. 2023; 192: 109989.
31	Mathews AM, Wysham NG, Xie JC, Qin XD, Giovacchini CX, Ekström M, et al. Hypercapnia in advanced chronic obstructive pulmonary disease: a secondary analysis of the national emphysema treatment trial. Chronic Obstr Pulm Dis. 2020; 7(4): 336-45.
32	Nolte PC, Häske D, Lefering R, Bernhard M, Casu S, Frankenhauser S, et al. Training to identify red flags in the acute care of trauma: who are the patients at risk for early death despite a relatively good prognosis? An analysis from the TraumaRegister DGU®. World J Emerg Surg. 2020; 15(1): 47.
33	Laredo M, Vandiedonck C, Miró Ò, González Del Castillo J, Alquézar-Arbé A, Jacob J, et al. Are there differences in the relationship between respiratory rate and oxygen saturation between patients with COVID-19 and those without COVID-19? Insights from a cohort-based correlational study. Emerg Med J. 2023; 40(12): 805-9. doi: 10.1136/emermed-2022-212882 pmid: 37788896

Variables	FiO₂ thresholds			P-value
Variables	0.21 (n=5,267)	0.22-0.49 (n=1,123)	≥ 0.5 (n=1,104)	P-value
Demographics
Sex at birth, female	2,214 (42.0)	447 (39.8)	437 (39.6)	0.170
Age, year	65 (49-79)	74 (61-84)	69 (54-80)	<0.001
Age, year
18-49	1,337 (25.4)	128 (11.4)	204 (18.5)	<0.001
50-74	2,069 (39.3)	449 (40.0)	462 (41.8)
>75	1,861 (35.3)	546 (48.6)	438 (39.7)
Transfer by ALS	3,114 (59.1)	744 (66.3)	980 (88.8)	<0.001
On-scene vital signs
RR, breaths/min	17 (14-19)	23 (17-29)	25 (15-32)	<0.001
Oxygen saturation, %	97 (96-99)	93 (89-96)	88 (78-94)	<0.001
SBP, mmHg	136 (118-153)	131 (108-151)	129 (100-151)	<0.001
DBP, mmHg	80 (68-91)	75 (61-89)	72 (56-90)	<0.001
HR, beats/min	81 (69-98)	93 (75-110)	100 (78-120)	<0.001
Temperature, °C	36 (35.9-36.5)	36.3 (36-36.8)	36.1 (35.6-36.7)	<0.001
GCS, points	15 (15-15)	15 (14-15)	12 (5-15)	<0.001
Prehospital POCT
pH	7.39 (7.35-7.42)	7.36 (7.31-7.42)	7.31 (7.14-7.37)	<0.001
pCO₂, mmHg	39 (33-44)	43 (35-51)	48 (37-65)	<0.001
pO₂, mmHg	32 (23-42)	29 (22-40)	23 (15-34)	<0.001
Bicarbonate, mEq	24.1 (21.9-26.7)	23.7 (21-27.3)	21.5 (17.6-26.1)	<0.001
BE, mmol/L	0.7 (-1.9; 1.9)	0.1 (-3.1; 2.2)	-2.6 (-7.6; 1.1)	<0.001
cSO₂, %	47 (38-67)	45 (33-66)	36 (23-54)	<0.001
Sodium, mmol/L	139 (137-141)	139 (136-141)	139 (136-141)	0.487
Potassium, mmol/L	4.1 (3.8-4.4)	4.1 (3.8-4.6)	4.1 (3.8-4.9)	0.331
TCO₂, mmol/L	25 (23-28)	26 (22-30)	27 (21-32)	<0.001
Hemoglobin, g/dL	14.2 (12.9-15.7)	13.9 (12.4-15.7)	13.9 (12.3-15.8)	<0.001
Glucose, mg/dL	121 (102-146)	139 (112-185)	155 (115-213)	<0.001
Lactate, mmol/L	1.87 (1.14-2.88)	2.51 (1.75-3.81)	3.69 (2.29-6.75)	<0.001
Creatinine, mgr/dL	0.87 (0.75-1.12)	1.02 (0.82-1.43)	1.14 (0.86-1.76)	<0.001
Urea, mg/dL	32 (24-45)	43 (30-62)	49 (30-75)	<0.001

Variables	FiO₂ thresholds
Variables	0.21	0.22-0.49	≥ 0.5
2-day mortality
Survivors	5,244	1,063	851
Non-survivors	23	60	253
7-day mortality
Survivors	5,191	1,023	786
Non-survivors	76	100	318
30-day mortality
Survivors	5,107	943	700
Non-survivors	160	180	404
90-day mortality
Survivors	4,985	869	622
Non-survivors	282	254	482
180-day mortality
Survivors	4,896	814	579
Non-survivors	371	309	525
365-day mortality
Survivors	4,746	751	546
Non-survivors	521	372	558

[1]	Jesús Jurado-Palomo, José Luis Martín-Conty, Begoña Polonio-López, Cristina Rivera Picón, Raúl López-Izquierdo, Carlos del Pozo Vegas, Pedro Ángel de Santos Castro, Ancor Sanz-García, Francisco Martín-Rodríguez. Prehospital critical care drug-therapy and 30-day mortality in patients with acute respiratory disease [J]. World Journal of Emergency Medicine, 2025, 16(1): 43-50.
[2]	Johan L. van Nieuwkerk, M. Christien van der Linden, Rolf J. Verheul, Merel van Loon-van Gaalen, Marije Janmaat, Naomi van der Linden. The impact of prehospital blood sampling on the emergency department process of patients with chest pain: a pragmatic non-randomized controlled trial [J]. World Journal of Emergency Medicine, 2023, 14(4): 257-264.
[3]	Zi-wei Ke, Yue Jiang, Ya-ping Bao, Ye-qin Yang, Xiao-mei Zong, Min Liu, Xiang-yun Guan, Zhong-qiu Lu. Intensivists’ response to hyperoxemia in mechanical ventilation patients: The status quo and related factors [J]. World Journal of Emergency Medicine, 2021, 12(3): 202-206.
[4]	Colin A. Meghoo, Stanislav Gaievskyi, Oleksandr Linchevskyy, Bindhu Oommen, Kateryna Stetsenko. Prehospital response to respiratory distress by the public ambulance system in a Ukrainian city [J]. World Journal of Emergency Medicine, 2019, 10(1): 42-45.
[5]	Linda Chokotho, Wakisa Mulwafu, Isaac Singini, Yasin Njalale, Kathryn H. Jacobsen. Improving hospital-based trauma care for road traffic injuries in Malawi [J]. World Journal of Emergency Medicine, 2017, 8(2): 85-90.
[6]	Andrew Fu Wah Ho, Pin Pin Pek, Stephanie Fook-Chong, Ting Hway Wong, Yih Yng Ng, Aaron Sung Lung Wong, Marcus Eng Hock Ong. Prehospital system delay in patients with ST-segment elevation myocardial infarction in Singapore [J]. World Journal of Emergency Medicine, 2015, 6(4): 277-282.
[7]	Özlem Köksal, Fatma Özdemir, Erol Armağan, Nuran Öner, Pınar Çinar Sert, Deniz Sigirli. Is routine pregnancy test necessary in women of reproductive age admitted to the emergency department? [J]. World Journal of Emergency Medicine, 2013, 4(3): 175-178.
[8]	Jin-jun Zhang, Li-dong Wang, Zhi Chen, Jun Ma, Jian-ping Dai. Medical care delivery at the Beijing 2008 Olympic Games [J]. World Journal of Emergency Medicine, 2011, 2(4): 267-271.
[9]	Venus WS Siu, Y Pau, PY Lok, Larry LY Lee, Simon YH Tang, Jimmy TS Chan. An evaluation of compliance and performance following the introduction of the Inter-Facility Transport Triage Guideline [J]. World Journal of Emergency Medicine, 2011, 2(2): 99-103.