IO, IO it's off to work we go…
Recent trials exploring the effectiveness of cardiac arrest drugs suggest that the effects are time-dependent, and that earlier drug administration may improve outcomes. Gaining intravenous (IV) access in out-of-hospital cardiac arrest (OHCA) is challenging and can be time-consuming. The intraosseous (IO), as compared with IV, drug route may facilitate more rapid drug administration; however, its effect on clinical outcomes is uncertain. International resuscitation guidelines recommend IV as the primary route for cardiac arrest but the use of IO as a primary route has increased by 60% in some systems.
The PARAMEDIC-3 trial was a pragmatic parallel group, open-label, randomised trial carried out across 11 UK emergency medical systems between November 2021 and July 2024. The protocol was published in volume 17 of Resuscitation Plus. The primary outcome was survival at 30 days, with secondary outcomes including favourable neurological outcome at hospital discharge and return of spontaneous circulation (ROSC). Patients were included if they were ≥18 years of age, sustained an out-of-hospital cardiac arrest, were attended by trial-trained paramedics, and who required vascular access for drug administration during ongoing cardiopulmonary resuscitation (CPR). Patients with known or apparent pregnancy were excluded.
There were 6082 participants randomised (3040 to IO; 3042 to IV). Participant numbers were significantly below the 15 000 planned sample size, so the outcomes need to be considered in light of this. There was 30-day survival recorded in 137 of 3030 (4.5%) in the IO group and 155 of 3034 (5.1%) in the IV group (adjusted odds ratio 0.945, 95% CI 0.676–1.322, p=0.741). A favourable neurological outcome at hospital discharge occurred in 80/2994 (2.7%) and 85/2986 (2.8%) in the IO and IV groups, respectively (adjusted odds ratio, 0.914, 95% CI 0.567–1.474). ROSC occurred at any time in 1092/3031 (36.0%) in the IO group and 1186/3035 patients (39.1%) in the IV group (adjusted odds ratio, 0.863; 95% CI 0.765–0.974). The researchers concluded that an IO-first strategy did not improve the rate of 30-day survival in adults with OHCA requiring drug therapy.
Why do fewer females survive cardiac arrest?
Difference in survival from OHCA has been documented between sexes, with some studies showing crude survival rates to 30 days being twice as high in males than in females. However, other studies have shown that if factors such as bystander CPR, initial cardiac rhythm and emergency medical services (EMS) arrival times, are considered, then the sex differences no longer exist. This suggests that while the biological sex of the patient may play a part, it does not fully explain the differences in OHCA survival.
This retrospective study sought to investigate the impact of potential mediating factors in the sex difference in survival after OHCA, using a large population-based cohort. Adult patients who had suffered non-traumatic OHCA cases where the Scottish Ambulance Service had attempted resuscitation were included in the study. The time span was from 1 April 2011–1 March 2020, with a pragmatic decision taken to exclude patients after this date owing to the possible impact of the COVID-19 pandemic.
The statistical methods used are beyond the scope of this summary but can be found in the full open-access article.
There were 20585 adult OHCA cases where resuscitation was attempted by EMS identified; however, 3932 EMSwitnessed arrests were excluded. The incidence of OHCA was higher in males than in females (55.8 versus 29.9 per 100000 population per year) and the proportion with initial shockable rhythm was 29.4% in males versus 17.4% in females. Bystander CPR was received by 56.7% of males versus 53.2% of females and 30-day survival was 8.2% in males and 6.2% in females. The crude odds ratio for survival was higher in males but after adjusting for confounding/mediating variables, sex was not associated with 30-day survival after OHCA. The findings indicate that initial cardiac rhythm and location of the arrest are potential mediators of higher 30-day OHCA survival in males. The authors suggest that improving the proportion of females presenting with initial shockable rhythms may reduce sex differences in survival.