Noradrenaline Vs Adrenaline in OHCA Patients

Epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation shock

(Bougouin et al. Intensive Care Med. 2022 Mar;48(3):300-310)

Blog Written by – Dr Jose Chacko

Study population and design: In this registry-based observational study, the authors identified patients admitted alive after OHCA to five university hospitals in France over a 7-y period between May 2011 and May 2018. Patients were in post resuscitation shock: the need for vasopressors for more than 6 h in spite of adequate fluid resuscitation while targeting a MAP >65 mm Hg.

Excluded: non-cardiac cause of cardiac arrest (trauma, drug overdose, drowning, etc)

Refractory cardiac arrest with no sustained ROSC

Refractory shock requiring ECMO

Not on intravenous epinephrine or norepinephrine

Patients on both drugs

Epinephrine and norepinephrine groups

1421 patients with post-resuscitation shock were initially identified, after exclusions, 766 patients were included, 481 (63%) were treated with norepinephrine infusion, and 285 (37%) with epinephrine infusion.

Among the study population, 73% of patients were male. The median time from collapse to CPR was 5 min (IQR 1–10) and from CPR to ROSC 22 min (IQR 15–30)

During the first 48 h of ICU, maximal epinephrine dose was 0.7 microg/kg/min (median), IQR 0.3–1.9, whereas in the norepinephrine group, maximal dose was 0.6 microg/kg/min (median), IQR 0.3–1.4. The Median duration of vasopressor support: epinephrine vs. norepinephrine 24h (IQR 12–48), vs 30 (IQR 19–48),

Overall, 235/766 (31%) patients survived to hospital discharge.

Primary outcome

All-cause hospital mortality: Higher with epinephrine (83% vs. 61%, P<0.001)

Secondary outcomes

Cardiovascular-specific mortality (44% vs. 11%, P<0.001)

Recurrent cardiac arrest (9% vs. 3%, P<0.001)

Mortality from refractory hemodynamic shock (35% vs. 9%, P<0.001)

Favourable neurological status 1: good recovery; 2: moderate disability

Poor neurological status at hospital discharge, defined as a Cerebral Performance Category score of 3–5 (3=severe disability), 4=vegetative state, and 5=death)

Favorable neurological status: epinephrine vs. norepinephrine: 15% vs. 37%, P<0.001

Multivariate logistic regression analysis including age, sex, bystander CPR, initial shockable rhythm, time from collapse to CPR, time from CPR to ROSC, epinephrine dose during resuscitation (before ROSC), arterial pH, myocardial dysfunction, targeted temperature management, and percutaneous coronary intervention: Epinephrine infusion was independently associated with all-cause mortality (odds ratio [OR] 2.6, 95%CI 1.4–4.7, P=0.002).

Epinephrine infusion was also associated with increased risk of cardiovascular mortality (adjusted OR [aOR] 5.5, 95%CI 3.0–10.3, P<0.001), ICU mortality (aOR 2.5 95%CI 1.4–4.4, P = 0.003), and an unfavorable neurological outcome (CPC 3–5 at hospital discharge: aOR 3.0, 95%CI 1.6–5.7, P=0.001)

A propensity score for continuous epinephrine use was developed based on the initial rhythm, time from collapse to CPR, time from CPR to ROSC; arterial pH; myocardial dysfunction; receiving hospital. After adjusting with propensity scores, receiving a continuous intravenous epinephrine infusion was significantly associated with all-cause mortality (OR 2.1, 95%CI 1.1–4.0, P=0.02). Similar results were found for cardiovascular- specific mortality (aOR 4.3, 95%CI 2.2–8.3, P < 0.001)

All-cause mortality was also compared on 93 pairs matched on a propensity score. In this analysis, continuous intravenous epinephrine infusion was associated, albeit non-significantly, with all-cause mortality (OR 1.8; 95%CI 0.94–3.4; P=0.08)

Sensitivity analysis performed after exclusion of moribund patients, restricted to patients with a cardiac arrest hospital prognosis (CAHP) score<150, restricted to patients with a CAHP score>150, or after exclusion of patients treated with epinephrine before ROSC found similar results.

Limitations

• Groups not matched at baseline
• Initial shockable rhythm less in the epinephrine group
• Time to ROSC less in the norepinephrine group
• MAP lower in the epinephrine group
• Admission pH lower in the epinephrine group
• Lactate higher in the epinephrine group
• Initial LV EF lower in the epinephrine group
• Targeted temperature management more in the norepinephrine group
• Several risk factors for poorer outcomes were more common in the epinephrine group, such as unshockable rhythm, longer time from CPR to ROSC, lower blood pH at admission, and myocardial dysfunction
• Limitations of an observational study with unidentified confounders
• Unknown biases
• Is there a dose-effect with adverse outcomes with epinephrine?