Published online Sep 9, 2026. doi: 10.5492/wjccm.119122
Revised: February 11, 2026
Accepted: May 9, 2026
Published online: September 9, 2026
Processing time: 219 Days and 3 Hours
Timely administration of adrenaline during in-hospital cardiac arrest (IHCA) with non-shockable rhythms is recommended, yet delays are common when drug administration depends on physician authorisation.
To evaluate whether empowering nurses to administer the first dose of adrenaline could reduce delays and im
In this study of prospectively collected registry data, the primary outcome of time to first dose of adrenaline in IHCA events with non-shockable rhythms (asystole/pulseless electrical activity) was compared between the pre-intervention phase (September 1, 2018 to November 26, 2019), when adrenaline administration was physician-led, and the post-intervention phase (November 27, 2019 to December 31, 2021), when nurse-led administration of adrenaline without physician order was implemented. Secondary outcomes included return of spontaneous circulation (ROSC), time to ROSC, 24-hour survival, and survival to discharge. Logistic regression analysis was performed to assess for factors associated with ROSC and whether timely adrenaline administration (defined as within 2-minutes) was independently associated with ROSC.
Among 450 IHCA events, 162 occurred in the pre-intervention and 288 in the post- intervention period. The mean (standard deviation) age was 52.5 (16.1) years; 63.1% were male. Timely adrenaline administration improved from 46% in the pre-intervention period to 74.3% (P < 0.001) in the post-intervention period, reducing the median (interquartile range) time to first dose from 4 (1-6) minutes to 2 (0-3) minutes (P < 0.001). Although this did not improve ROSC rates, pre-post intervention (56.8% vs 58.3%, P = 0.74), ROSC was achieved faster (P < 0.001) in the post-intervention period when compared with the pre-intervention period. Combining pre- and post-intervention data, timely adrenaline administration when compared with delayed administration was associated with shorter time to ROSC (P = 0.006) but did not improve survival. On multivariate logistic regression analysis, shorter time to Cardiac Arrest and Resuscitation Team arrival and identification of a reversible cause were independently associated with ROSC, whereas the time to first dose of adrenaline was not.
Nurse-led early adrenaline administration during IHCA significantly reduced treatment delays and enhanced resuscitation efficiency, though it did not translate to reduced hospital mortality. This model is feasible in low- and middle-income settings and underscores the value of system-level empowerment to improve IHCA care.
Core Tip: We evaluated whether empowering nurses to administer the first dose of adrenaline for in-hospital cardiac arrest for non-shockable rhythms could reduce delays and improve outcomes. In this pre-post intervention study spanning over 3 years, we observed that nurse empowerment resulted in a reduction in the time to administer adrenaline, leading to faster return of spontaneous circulation. However, this did not translate to improved mortality.
- Citation: Chacko B, Jacob AS, Thomas L, L A, John SAS, Sanghi AE, P NR, Rao SV, Adhikari DD, Vijayananthan S, Anita EA, V A, Yadav B, Peter JV. Impact of nurse empowerment for early adrenaline administration for in-hospital cardiac arrest resuscitation: A pre-post intervention study. World J Crit Care Med 2026; 15(3): 119122
- URL: https://www.wjgnet.com/2220-3141/full/v15/i3/119122.htm
- DOI: https://dx.doi.org/10.5492/wjccm.119122
In-hospital cardiac arrest (IHCA) is a major global health concern that is associated with high morbidity and mortality. The incidence ranges from 1.5 to 6 per 1000 hospital admissions, with survival to discharge averaging 20%-25% in high-income countries and less than 10% in low- and middle-income countries (LMICs)[1-3]. This disparity reflects differences in healthcare infrastructure, staff training, and post-resuscitation care. Despite advances in resuscitation science, IHCA outcomes remain suboptimal, highlighting the need for strategies to bridge the gap between evidence and practice[4-6]. The “chain of survival”, endorsed by international resuscitation councils, stresses early recognition of cardiac arrest, prompt high-quality cardiopulmonary resuscitation (CPR), rapid defibrillation, and timely pharmacologic intervention[1,3]. Guidelines recommend administering 1 mg of adrenaline every 3-5 minutes, with emphasis on early administration for non-shockable rhythms[1,2]. Although adrenaline increases the likelihood of return of spontaneous circulation (ROSC), its effect on long-term survival and neurological recovery is inconclusive.
Evidence on adrenaline timing comes from both out-of-hospital and IHCA studies. The Pre-hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest (PARAMEDIC2) trial showed that adrenaline improved 30-day survival but not favourable neurological outcomes in out-of-hospital cardiac arrests (OHCA). Secondary analyses found survival and neurological outcomes declined with delayed drug administration, supporting earlier use, though extrapolation to IHCA requires caution[7]. IHCA-specific observational studies have similarly shown stepwise outcome declines with delays in resuscitation interventions[8]. Bircher et al[5] found that epinephrine within 2-minutes of CPR in IHCA improved survival, while delays to defibrillation or epinephrine caused stepwise outcome declines, reducing survival odds by up to 46%, underscoring the need for rapid, coordinated resuscitation. Notably, the study by Khera et al[9] recommended further research to determine whether faster epinephrine administration improves patient outcomes.
Collectively, these findings support early adrenaline access as a quality improvement priority. Delays in first-dose delivery often result from hierarchical authorization, workflow inefficiencies, physician-dependent protocols, and logistical barriers, especially in non-critical care areas and LMIC settings. Although nurses are usually first responders and trained in intravenous drug delivery, restrictions on independent adrenaline use without physician approval can cause avoidable delays. Studies from high-performing hospitals show that nurse-led resuscitation improves guideline adherence and outcomes[6,10,11]. In this context, a policy was introduced in 2019 in a tertiary care hospital in a LMIC setting to empower nurses to administer the first dose of adrenaline without physician authorization for non-shockable IHCA. This study evaluated the impact of this policy change on time to adrenaline administration, ROSC and hospital survival in a pre- post-intervention study.
This study was a retrospective analysis of prospectively collected data from an institutional cardiac arrest registry. The registry was initiated in September 2018 as part of an institutional quality assurance program to systematically document IHCA events. The nurse-led adrenaline administration protocol was introduced in November 2019 as a service improvement initiative following internal quality review meetings that identified delays in first-dose adrenaline administration. After sufficient follow-up data in the registry, it was decided to formally evaluate outcomes and process metrics before and after implementation of this protocol using the registry dataset.
All adult inpatients (≥ 18 years) experiencing IHCA with an initial non-shockable rhythm, either asystole or pulseless electrical activity (PEA), were included. The pre- intervention phase covered September 1, 2018 to November 26, 2019, while the post-intervention phase extended from November 27, 2019 to December 31, 2021. Exclusion criteria were patients in intensive care units or operating theatres, those with documented “do not resuscitate” orders prior to arrest, pediatric patients (< 18 years), and OHCA. Institutional Ethics Committee approval was obtained on October 27, 2021 (No. 14322). Since the study involved secondary analysis of routinely collected, de-identified clinical registry data and did not involve additional patient contact or intervention, the requirement for individual informed consent was waived by the Ethics Committee.
The institution runs a structured training in cardiac arrest recognition and basic life support and conducts simulation-based workshops and competency assessments to ensure proficiency, consistent with international recommendations for high-fidelity resuscitation training[1,2,12]. During quality audits, it was recognized that there were delays in administering the first dose of adrenaline for IHCA. One of the key factors was the requirement of physician authorization for the administration of adrenaline. To improve the effectiveness of CPR, a decision was taken to empower nurses to administer the first dose of adrenaline upon recognition of a non-shockable cardiac arrest without physician authorization. The initiative reflected the best international practices for minimizing pharmacological delays, improving resuscitation efficiency, and strengthening system responsiveness within the hospital’s cardiac arrest management framework[13,14]. On November 27, 2019, the hospital implemented the policy. Under the revised protocol, nurses were authorized to administer the first dose of adrenaline (1 mg IV) immediately after confirming cardiac arrest in patients with non-shockable rhythms such as PEA or asystole, without awaiting physician approval.
Prior to the rollout of the policy, structured training sessions were conducted for the ward nurses covering recognition of cardiac arrest and indications for early adrenaline administration in non-shockable arrests. Training included didactic sessions and reinforcement through existing institutional simulation-based resuscitation training programs. No changes were made to medication availability or crash cart placement during the intervention. Adrenaline was already stocked in standard resuscitation carts across the institution. Adherence to the protocol was monitored through routine cardiac arrest documentation and monthly quality review meetings. First responder audits were also conducted on a regular basis to assess adherence to this protocol.
During the coronavirus disease 2019 (COVID-19) pandemic period (first wave started in June 2020, peaking by September 2020 and waning by December 2020; second wave started in March 2021, peaked by May 2021 and waned by August 31, 2021), institutional resuscitation protocols included additional infection-control measures such as personal protective equipment requirements, modifications to team entry and composition. The COVID wards were co-located, and cardiac arrests were attended by the medical critical care team, who were already taking care of COVID patients in the intensive care unit. The passages to these wards were restricted, and hence the team could move to the respective wards in their personal protective equipment.
The cardiac arrest registry used for this study was initiated in September 2018 as part of a hospital-wide quality assurance program to monitor IHCA care. Data that included standardized documentation of IHCA events, a detailed Cardiac Arrest and Resuscitation Team (CART) protocol with a checklist of required interventions, were prospectively recorded during resuscitation events by the designated CART scribing nurse using structured documentation forms maintained by the quality management cell. Collected variables encompassed demographics, comorbidities, location and characteristics of arrest, initial rhythm and timing, CART activation and arrival, adrenaline timing, time to ROSC, ROSC status, survival at 24-hour, and survival to discharge. This data was recorded as part of routine clinical documentation and not retrospectively abstracted for research purposes. IHCA was defined as cessation of cardiac mechanical activity, confirmed by unresponsiveness, apnea, and absence of a palpable central pulse, necessitating CPR initiation. Timely administration of adrenaline was defined as the administration of the drug within 2-minutes of cardiac arrest recognition. ROSC was defined as the reappearance of a palpable pulse with sustained spontaneous circulation for at least 20 minutes.
The primary outcome of the study was the time to the first dose of adrenaline in IHCA with a non-shockable rhythm. Secondary outcomes included ROSC, time to ROSC, survival at 24 hours, and survival to discharge. CART system responsiveness was assessed in terms of time to CART activation and arrival, CPR cycles required, pharmacological interventions, management of reversible causes and post ROSC management. Logistic regression analysis evaluated factors associated with ROSC and whether timely adrenaline administration (within 2-minutes) independently predicted ROSC.
Data analysis was performed using IBM SPSS Statistics, version 25 (IBM Corp., Armonk, NY, United States). Continuous variables were tested for normality using the Shapiro-Wilk test. Normally distributed data were presented as mean with standard deviation and compared using Student’s t-test, while non-normally distributed data were summarized as median with interquartile range (IQR) and analyzed using the Mann-Whitney U test. Categorical variables were expressed as frequencies and percentages, and intergroup differences were assessed using the χ2 or Fisher’s exact test when expected counts were < 5. Time-dependent parameters, including time to first adrenaline, time to ROSC, and total resuscitation duration, were analyzed as continuous variables. Missing data were managed using complete-case analysis after confirming < 5% missingness for key outcomes. Bivariate logistic regression analyses were performed to identify variables associated with ROSC and hospital mortality. Factors identified on bivariate logistic regression analysis were incorporated into a multivariable logistic regression model to identify independent predictors of ROSC and hospital mortality. They were expressed as odds ratios (ORs) with 95% confidence intervals (CIs).
A post-hoc sensitivity analysis was performed, excluding the COVID-19 period, since the case mix admitted to the hospital was likely to be different during this period due to the restrictions on accessing healthcare, which could have influenced illness severity and the additional precautions that needed to be undertaken during the pandemic, which could have influenced the response to IHCA. In addition, an interrupted time series analysis was performed to assess whether the COVID-19 pandemic influenced the timely administration of adrenaline. Statistical significance was defined as P < 0.05 (two-tailed).
Of the 467 IHCA events during the study period, 450 patients with cardiac arrest due to non-shockable rhythms (asystole or PEA) were included. Patients with shockable rhythms (n = 17, 3.5%) were excluded; 10 had ventricular fibrillation, and 7 had pulseless ventricular tachycardia. Of the 450 patients in the study cohort, 162 were in the pre-intervention period and 288 in the post-intervention period (Figure 1). Most patients had asystole (n = 425, 94.4%) on rhythm check, while a small proportion had PEA (n = 25, 5.6%). The mean ± SD age of the entire cohort was 52.5 ± 16.1 years and similar in both groups; 63.1% were male (Table 1). The IHCA events occurred with similar frequency during daytime and nighttime hours (46.9% vs 51.7%; P = 0.33). A majority occurred during weekdays (73%). Nearly all events were witnessed (98.9%), and most patients were on continuous monitoring prior to arrest (92.4%). These were similar in the pre- and post-intervention periods.
| Parameter | All patients (n = 450) | Pre-intervention (n = 162) | Post intervention (n = 288) | P value |
| Demographics | ||||
| Age, mean ± SD years | 52.5 ± 16.1 | 53.3 ± 16.1 | 52.1 ± 16.1 | 0.44 |
| Gender, male | 284 (63.1) | 103 (63.6) | 181 (62.9) | 0.92 |
| Details of cardiac arrest | ||||
| Initial arrest rhythm | ||||
| Asystole | 425 (94.4) | 151 (93.2) | 274 (95.1) | 0.40 |
| PEA | 25 (5.6) | 11 (6.8) | 14 (4.9) | |
| Witnessed arrest | 445 (98.9) | 159 (98.2) | 286 (99.3) | 0.36 |
| Monitoring prior to arrest | 416 (92.4) | 149 (92) | 267 (92.7) | 0.85 |
| Time to activate CART, median (IQR) minutes | 2 (1, 5) | 4 (1, 7) | 2 (0, 3) | < 0.001 |
| Time to CART arrival, median (IQR) minutes | 5 (3, 8) | 6.5 (4, 10) | 4 (3, 6) | < 0.001 |
| Time to CPR initiation, median (IQR) minutes | 0 (0, 0) | 0 (0, 0) | 0 (0, 0) | 0.52 |
| Reversible cause identified | 315 (70) | 87 (53.7) | 228 (79.2) | < 0.001 |
Several resuscitation process indicators differed between the pre- and post-intervention periods. The median (IQR) time to CART activation decreased from 4 (IQR: 1-7) minutes in the pre-intervention period to 2 (0-3) minutes in the post-intervention period, while the median time to CART arrival decreased from 6.5 (4-10) minutes to 4 (3-6) minutes (both P < 0.001). A reversible cause of arrest was identified more frequently (P < 0.001) during the post-intervention period (79.2%) when compared with the pre-intervention period (53.7%). The median (IQR) time to administration of the first dose of adrenaline was also shorter in the post-intervention period, decreasing from 4 (1-6) minutes to 2 (0-3) minutes (P < 0.001). A greater proportion of patients (P < 0.001) received adrenaline within 2-minutes of arrest recognition in the post-intervention period (74.3%) when compared with the pre-intervention period (46%). These differences occurred alongside other concurrent improvements in resuscitation process metrics during the study period, including faster CART activation and arrival of the CART members. The number of doses required to achieve ROSC was significantly higher in the post-intervention period (Table 1). The number of cycles of CPR and the number who attained ROSC were similar during the two periods. However, survival to hospital discharge was lower (P = 0.05) in the post-intervention period (10.1%) when compared with the pre-intervention period (16.7%).
Overall, 260 patients (57.8%) achieved ROSC. The proportion of patients who achieved ROSC was similar (P = 0.74) in the pre- and post-intervention periods (Table 2). However, the time to achieve ROSC reduced significantly (P < 0.001) from 20 minutes (IQR: 12-30) in the pre-intervention period to 12 minutes (IQR: 8-23) in the post-intervention period. The time to administer the first dose of adrenaline was significantly lower, and the proportion of patients who received adrenaline within 2-minutes was significantly higher in the post-intervention period among those who achieved ROSC (Table 2). The time to administer the first dose of adrenaline was significantly lower, and the proportion of patients who received adrenaline within 2-minutes was significantly higher in the post-intervention period among those who achieved ROSC (Table 2). In this subset of patients who achieved ROSC, the median doses of adrenaline required to achieve ROSC were 3 (IQR: 2-4) and similar in both periods (P = 0.65). A reversible cause was identified in more patients during the post- intervention period. Hospital mortality was higher in the post-intervention period when compared with the pre-intervention period (OR = 1.79, 95%CI: 0.97-3.26). There was no difference in the number of patients who achieved ROSC in the two periods (OR = 1.10, 95%CI: 0.74-1.67). However, timely administration of adrenaline was significantly more likely in the post-intervention period when compared with the pre-intervention period (OR = 3.39, 95%CI 2.18-5.29).
| Parameter | All patients (n = 260) | Pre-intervention (n = 92) | Post intervention (n = 168) | P value |
| Time to 1st adrenaline, median (IQR) minutes | 2 (0, 4) | 3 (0, 6) | 1 (0, 2) | < 0.001 |
| Timely adrenaline administration1 | 166 (68.6) | 40 (48.8) | 126 (78.8) | < 0.001 |
| Time to ROSC, median (IQR), minutes | 15 (8, 26) | 20 (12, 30) | 12 (8, 23) | < 0.001 |
| Number of cycles of CPR, median (IQR) | 7 (4, 10) | 8 (5, 11) | 6 (4, 10) | 0.06 |
| Number of doses of adrenaline, median (IQR) | 3 (2, 4) | 3 (2, 4) | 3 (2, 4) | 0.65 |
| Reversible cause identified | 198 (76.2) | 53 (58.2) | 145 (85.8) | < 0.001 |
| Shifted to ICU2 | 188 (72.3) | 72 (79.3) | 116 (68.6) | 0.08 |
| Survival at 24-hour | 142 (54.6) | 58 (63.0) | 84 (49.7) | 0.04 |
| Survival to hospital discharge among ROSC | 56 (21.5) | 27 (29.7) | 29 (17.2) | 0.03 |
Since the time to adrenaline administration is likely to impact outcomes in cardiac arrest, and given that timely administration of adrenaline was achieved in both periods in a proportion of patients, a comparison was made between those who had timely administration of adrenaline vs those who did not in the entire cohort (Table 3). The time to CART activation and the number of cycles of CPR were significantly lower in the group that received timely adrenaline when compared with those who did not receive the first dose of adrenaline within 2-minutes. A reversible cause was identified in more patients among those who received adrenaline promptly (P < 0.001). More patients were likely to achieve ROSC (P = 0.04) when the first dose of adrenaline was administered in a timely manner (60.6%) when compared with those who had delayed administration of adrenaline (50%). The median time to achieve ROSC was also significantly faster (P = 0.006) at 14 minutes (IQR: 8-26) when adrenaline was administered within 2-minutes when compared with 20.5 minutes (IQR: 12-30) among those who received it beyond 2-minutes. However, timely administration of adrenaline was not associated with survival at 24-hour (P = 0.58) or hospital survival (P = 0.29).
| Parameter | All patients (n = 426)2 | Adrenaline ≤ 2 minutes | Adrenaline > 2 minutes | P value |
| Age, mean ± SD years | 52.7 ± 16.0 | 51.7 ± 16.0 | 54.5 ± 16.0 | 0.08 |
| Gender, male | 270 (63.4) | 172 (62.8) | 98 (64.5) | 0.75 |
| Initial arrest rhythm | ||||
| Asystole | 402 (94.4) | 261 (95.3) | 141 (92.8) | 0.28 |
| PEA | 24 (5.6) | 13 (4.7) | 11 (7.2) | |
| Time to CART activation, median (IQR) | 2 (1, 5) | 1 (0, 3) | 3 (1, 6) | < 0.001 |
| Number of cycles of CPR, median (IQR) | 10 (6, 16) | 9 (5, 15) | 10 (7, 16) | 0.02 |
| Number of adrenaline doses, median (IQR) | 4 (2, 7) | 4 (3, 7) | 4 (2, 6) | 0.08 |
| Reversible cause identified | 304 (71.4) | 213 (77.7) | 91 (60) | < 0.001 |
| Outcomes among those who achieved ROSC | ||||
| Number who achieved ROSC | 242 (56.8) | 166 (60.6) | 76 (50) | 0.04 |
| Time to achieve ROSC, median (IQR) | 16 (10, 28) | 14 (8, 26) | 20.5 (12, 30) | 0.006 |
| Survival at 24 hours following ROSC | 130 (53.7) | 87 (52.4) | 43 (56.6) | 0.58 |
| Survival to hospital discharge among ROSC | 47 (19.4) | 29 (17.5) | 18 (23.7) | 0.29 |
Bivariate and multivariate logistic regression analyses were done to identify predictors of ROSC and mortality. On bivariate analysis, younger age, PEA rhythm, shorter times to CART activation/arrival, faster adrenaline administration, and identification of reversible causes were associated with a higher odds of achieving ROSC (Table 4). Multivariate logistic regression analysis was performed, incorporating age, type of rhythm, time to CART arrival, time to first dose of adrenaline, and identification of a reversible cause for the arrest. A shorter time to CART arrival (OR = 0.96, 95%CI: 0.92-1.0, P = 0.03) and a reversible cause (OR = 2.0, 95%CI: 1.21-3.34, P = 0.007) were independently associated with ROSC. On multivariate logistic regression analysis on the predictors of hospital mortality (Table 5), the post-intervention period (OR = 1.89, 95%CI: 1.04-3.43, P = 0.04) and number of CPR cycles (OR = 1.19, 95%CI: 1.11-1.28, P < 0.001) were independently associated with mortality.
| Parameter | Bivariate analysis OR (95%CI) | P value | Multivariate analysis OR (95%CI) | P value |
| Age | 0.99 (0.98-1.00) | 0.052 | 0.98 (0.97-1.0) | 0.14 |
| Female gender | 0.93 (0.63-1.37) | 0.78 | ||
| Post-intervention period | 1.11 (0.75-1.64) | 0.61 | ||
| PEA arrest | 0.47 (0.2-1.06) | 0.072 | 0.45 (0.19-1.07) | 0.07 |
| Time to CART activation | 0.95 (0.91-0.98) | 0.0063 | ||
| Time to CART arrival | 0.94 (0.91-0.98) | 0.0022 | 0.96 (0.92-1.00) | 0.05 |
| Time to first adrenaline | 0.94 (0.89-0.99) | 0.032 | 0.97 (0.92-1.03) | 0.33 |
| Adrenaline within 2 minutes | 0.65 (0.44-0.97) | 0.043 | ||
| Reversible cause | 1.99 (1.32-3.0) | 0.0012 | 1.71 (1.10-2.67) | 0.02 |
| Parameter | Bivariate analysis OR (95%CI) | P value | Multivariate analysis OR (95%CI) | P value |
| Age | 1.01 (1.0-1.03) | 0.092 | 1.01 (0.99-1.03) | 0.19 |
| Female gender | 1.06 (0.59-1.90) | 0.85 | ||
| Post-intervention period | 1.79 (1.02-3.14) | 0.042 | 1.89 (1.04-3.43) | 0.04 |
| PEA arrest | 0.73 (0.24-2.22) | 0.58 | ||
| Time to CART activation | 0.98 (0.93-1.04) | 0.53 | ||
| Time to CART arrival | 0.98 (0.93-1.03) | 0.42 | ||
| Time to first adrenaline | 1.0 (0.92-1.08) | 0.96 | ||
| Adrenaline within 2 minutes | 0.88 (0.47-1.65) | 0.69 | ||
| Number of CPR cycles | 1.19 (1.15-1.28) | < 0.0012 | 1.19 (1.11-1.28) | < 0.001 |
| Reversible cause | 1.12 (0.62-2.05) | 0.71 |
Table 6 presents a comparison of the key outcomes between the pre- and post-intervention periods for all patients and excluding IHCA during the COVID period. The results of the sensitivity analysis, excluding the COVID period, were largely consistent with the main analysis. Of note, the administration of adrenaline remained significantly higher in the post-intervention period when compared to the pre-intervention period (OR = 3.47, 95%CI: 2.10-5.74; P < 0.001), despite excluding the COVID period, confirming sustained improvement in adherence to resuscitation protocols. The observed increase in mortality in the post-intervention period was no longer statistically significant after excluding COVID-era cases (P = 0.14), suggesting that the mortality difference in the pre-post intervention period could have been influenced by pandemic-related factors. Interrupted time series analysis demonstrated that the post-intervention period was associated with significantly higher odds of timely adrenaline administration than the pre-intervention period (OR = 1.33, 95%CI: 1.21-1.48, P < 0.001), indicating a significant level change following the intervention. There was no significant underlying temporal trend over time (OR = 1.00, 95%CI: 0.99-1.01, P = 0.19), and COVID-19 status was not associated with timely administration (OR = 0.99, 95%CI: 0.88-1.10, P = 0.81).
| Discrete variables | All patients | Excluding COVID era | ||
| OR/median difference (95%CI) | P value | OR/median difference (95%CI) | P value | |
| Timely adrenaline2 | 3.39 (2.18-5.29) | < 0.001 | 3.47 (2.10-5.74) | < 0.001 |
| Number obtained ROSC | 1.10 (0.74-1.67) | 0.61 | 1.19 (0.75-1.89) | 0.43 |
| Number shifted to ICU | 0.84 (0.56-1.27) | 0.39 | 0.82 (0.52-1.29) | 0.37 |
| Survival at 24-hour | 0.74 (0.48-1.14) | 0.15 | 0.84 (0.52-1.36) | 0.46 |
| Mortality | 1.79 (0.97-3.26) | 0.04 | 1.61 (0.82-3.21) | 0.14 |
| Time to 1st adrenaline, minutes | 2 (1-2) | < 0.001 | 2 (1-2) | < 0.001 |
| No. of doses of adrenaline | -1 (-1 to 0) | 0.007 | -1 (-1 to 0) | 0.01 |
| No. of cycles of CPR | 0 (-2 to 1) | 0.62 | 0 (-1 to 1) | 0.80 |
This study evaluated the impact of a nurse empowerment protocol that authorized ward nurses to initiate adrenaline administration during IHCA. In the post-intervention period, several resuscitation process indicators improved, including shorter times to CART activation, faster CART arrival, and earlier administration of the first dose of adrenaline, with a 50% reduction in the median time to first adrenaline administration from 4 minutes to 2 minutes, which resulted in a shorter time for ROSC from 20 minutes to 12 minutes. However, these improvements in resuscitation process metrics did not translate into improved patient-centred outcomes. The proportion of patients achieving ROSC was similar between the two periods, and survival to hospital discharge was lower in the post-intervention period. These findings suggest that while system-level process changes may improve the timeliness of resuscitation interventions, their impact on survival outcomes may be limited by other clinical and contextual factors.
International evidence supports nurse-administered adrenaline as a safe and effective practice. Studies from multiple settings report faster drug delivery and improved process metrics with nurse-led interventions and enhanced adherence to guidelines[15-19]. To our knowledge, this is one of the first systematic evaluations of nurse-led adrenaline administration in India, extending the evidence base to an LMIC context. Structured training, policy support, and cultural change enabled effective nurse-led intervention.
In our study, although the proportion of ROSC was similar (P = 0.74) in the pre- and post-intervention periods, timely administration of adrenaline was associated with a significantly higher (P = 0.04) probability of achieving ROSC. These findings are consistent with the study by Andersen et al[3], who observed that each minute’s delay reduced ROSC probability by 10%-15% and the study by Perkins et al[7], who reported improved ROSC with timely adrenaline administration[3,5,7,20]. However, in contrast to the study by Bakhsh et al[20], a higher probability of ROSC did not translate to a survival benefit in our patients. Despite these improvements in timeliness, the proportion of patients achieving ROSC and survival outcomes did not differ significantly between the pre- and post-intervention periods. This observation is consistent with prior IHCA and OHCA studies demonstrating that earlier epinephrine administration may improve resuscitation efficiency and short-term physiological endpoints without necessarily translating to improved survival or neurological outcomes[5,9].
The dissociation between ROSC improvement and survival is consistent with the Pre-hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest (PARAMEDIC2) trial[4], which showed early ROSC benefits without survival gains. Several factors may explain the absence of survival improvement in our study. Multivariate analysis indicated that reversible causes were stronger predictors of ROSC than early adrenaline alone. High prevalence of non- shockable rhythms, substantial comorbidity burden, variability in post-arrest care, and broader system constraints may be context-specific factors in our setting that could have limited survival outcomes, although these were not directly evaluated in our cohort. The post-intervention period also coincided with increased caseload and the COVID-19 pandemic, which may have contributed to additional operational strain. The sensitivity analysis, excluding the COVID era, did not materially alter the study findings, reinforcing the robustness of the intervention effect - particularly the improvement in timely adrenaline administration - while indicating that differences in mortality were likely confounded by pandemic-related influences.
From a health systems perspective, these findings are particularly relevant for LMICs such as India, where hierarchical structures and physician-dependent drug authorization often delay treatment. Barriers such as delayed physician availability, high patient loads, and workflow inefficiencies are common contributors to IHCA treatment delays. Nurse empowerment offers a pragmatic, scalable, and low-cost effective strategy to address these modifiable process barriers. Beyond improving timeliness, the policy also appeared to enhance teamwork and adherence to Advanced Cardiovascular Life Support standards, as reflected in faster CART activation and improved coordination. This suggests that nurse empowerment can foster broader cultural change, promoting shared accountability, interprofessional collaboration, and consistent protocol adherence. Sustainability of such protocols depends on institutional investment in structured simulation training, medicolegal safeguards, and leadership support. Moving toward multidisciplinary, team-based resuscitation models is vital for realizing the full potential of nurse-led interventions[20,21]. This study has several notable strengths. It addresses an urgent quality improvement issue in an LMIC setting characterized by frequent delays in IHCA response. The relatively large sample size (> 400 cardiac arrests) strengthens the robustness of findings, and the pre-post design allows for pragmatic evaluation of real-world impact. The inclusion of both process metrics (time to adrenaline, time to ROSC) and patient outcomes (ROSC, survival) offers a comprehensive view of system performance.
This study has several limitations. First, as a single-centre, pre-post observational study conducted at a tertiary academic institution, causal inference is limited, and findings may not be generalizable to all hospital settings. Second, the study may be underpowered to detect small absolute differences in ROSC or survival attributable to earlier adrenaline administration alone. As this was a pragmatic quality-improvement evaluation, a formal a priori power calculation was not performed. Accordingly, null or non-significant findings with respect to ROSC and survival should be interpreted with caution, and larger, ideally multicentre studies are required to reliably estimate the clinical impact of earlier adrenaline administration in IHCA. Third, baseline illness severity and post-arrest care processes were not systematically captured, limiting the interpretation of survival outcomes. Differences in comorbidity burden between study periods and potential healthcare system disruptions related to the COVID-19 pandemic may also have introduced residual confounding that could not be fully controlled.
Another limitation relates to rhythm classification during initial arrest recognition. Eligibility for early adrenaline administration depended on bedside identification of non-shockable rhythms by ward staff. Formal audit data comparing the initial rhythm interpretation documented by nursing staff with subsequent CART or physician confirmation were not systematically collected in the registry. Therefore, potential misclassification of the initial rhythm cannot be excluded and may have influenced both treatment decisions and exposure classification. Additionally, reliance on registry-based timing data may introduce minor measurement imprecision, although standardized documentation and audit processes were used to mitigate this risk.
Because ROSC and survival are influenced by CPR quality and downstream post-arrest care, future evaluations of resuscitation process interventions could be strengthened by incorporating objective physiologic markers of CPR effectiveness, such as capnography-derived end-tidal carbon dioxide trends[22]. Finally, neurological outcomes and long-term functional status were not systematically assessed in this study. Survival alone does not fully reflect the quality of recovery following cardiac arrest, and neurological status and disposition quality are increasingly recognized as critical patient-centred outcomes in cardiac arrest research. Because the registry primarily captured resuscitation processes and short-term outcomes, follow-up in this study was limited to survival to hospital discharge. Future evaluations of resuscitation system interventions should incorporate standardized neurological outcome measures, longer-term follow-up, and structured post-arrest care metrics to more comprehensively assess the clinical impact of such interventions. In summary, nurse-initiated adrenaline improved timeliness and system responsiveness, enhancing ROSC but not survival. These findings underscore both the promise of nurse-led interventions and the critical need for comprehensive post-arrest care and system-level strengthening to improve survival outcomes.
Empowering nurses to administer adrenaline early during IHCA substantially shortened treatment delays and enhanced critical resuscitation metrics, including time to drug delivery, ROSC, and overall CPR performance. These results mirror the international evidence linking early adrenaline to improved perfusion, even though long-term survival benefits remain inconsistent. Importantly, this low-cost, protocol-driven nurse-led strategy is both feasible and scalable, offering value in LMICs where hierarchical barriers and physician-dependent workflows commonly impede timely intervention.
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