The physiologic response to rescue therapy with vasopressin versus epinephrine during experimental pediatric cardiac arrest

Abstract

Aim: Compare vasopressin to a second dose of epinephrine as rescue therapy after ineffective initial doses of epinephrine in diverse models of pediatric in-hospital cardiac arrest.

Methods: 67 one- to three-month old female swine (10-30 kg) in six experimental cohorts from one laboratory received hemodynamic-directed CPR, a resuscitation method where high quality chest compressions are provided and vasopressor administration is titrated to coronary perfusion pressure (CoPP) ≥20 mmHg. Vasopressors are given when CoPP is <20 mmHg, in sequences of two doses of 0.02 mg/kg epinephrine separated by minimum one-minute, then a rescue dose of 0.4 U/kg vasopressin followed by minimum two-minutes. Invasive measurements were used to evaluate and compare the hemodynamic and neurologic effects of each vasopressor dose.

Results: Increases in CoPP and cerebral blood flow (CBF) were greater with vasopressin rescue than epinephrine rescue (CoPP: +8.16 [4.35, 12.06] mmHg vs. + 5.43 [1.56, 9.82] mmHg, p = 0.02; CBF: +14.58 [-0.05, 38.12] vs. + 0.00 [-0.77, 18.24] perfusion units (PFU), p = 0.005). Twenty animals (30%) failed to achieve CoPP ≥20 mmHg after two doses of epinephrine; 9/20 (45%) non-responders achieved CoPP ≥20 mmHg after vasopressin. Among all animals, the increase in CBF was greater with vasopressin (+14.58 [-0.58, 38.12] vs. 0.00 [-0.77, 18.24] PFU, p = 0.005).

Conclusions: CoPP and CBF rose significantly more after rescue vasopressin than after rescue epinephrine. Importantly, CBF increased after vasopressin rescue, but not after epinephrine rescue. In the 30% that failed to meet CoPP of 20 mmHg after two doses of epinephrine, 45% achieved target CoPP with a single rescue vasopressin dose.

Keywords: Cardiac arrest; Cardiopulmonary resuscitation; Cerebral blood flow; Coronary perfusion pressure; Epinephrine; Pediatrics; Vasopressin.

Fig. 1

Hemodynamic-directed CPR protocol. CPR = cardiopulmonary resuscitation; ETT = endotracheal tube; VF = ventricular fibrillation; HD = hemodynamic-directed; SBP = systolic blood pressure; CoPP = coronary perfusion pressure; ROSC = return of spontaneous circulation

Fig. 2

Study population enrollment and characteristics.

Fig. 3

(a) Coronary perfusion pressure during cardiac arrest in the total cohort (n = 67). (b) Coronary perfusion pressure during cardiac arrest in a population of epinephrine non-responders (n = 20), defined by coronary perfusion pressure < 20 mmHg after both doses of epinephrine. (c) Coronary perfusion pressure during cardiac arrest in a sub-population of subjects who did not achieve coronary perfusion pressure ≥ 20 mmHg after epinephrine but did achieve ≥ 20 mmHg after vasopressin (n = 9). legend: The x-axis reflects time during CPR. Time is discontinuous in the figure because vasopressors were delivered on an as-needed basis when CoPP <20 mmHg. The first two vertical lines represent the first and second epinephrine doses and the third vertical line represents the vasopressin dose. The one minute of data following each epinephrine dose and the two minutes of data following the vasopressin dose are depicted. The dashed, horizontal line depicts the CoPP goal of 20 mmHg.

Fig. 4

(a) Cerebral blood flow during cardiac arrest in the total cohort of subjects with evaluable cerebral blood flow data (n = 30). (b) Cerebral blood flow during cardiac arrest in the total cohort of subjects with evaluable cerebral blood flow data who were epinephrine non-responders (n = 23), defined by coronary perfusion pressure < 20 mmHg after both doses of epinephrine. (c) Cerebral blood flow during cardiac arrest in the total cohort of subjects with evaluable cerebral blood flow data, who did not achieve coronary perfusion pressure ≥ 20 mmHg after epinephrine but did achieve ≥ 20 mmHg after vasopressin (n = 7). legend: “The x-axis reflects time during CPR discontinuously because of vasopressors were delivered on an as-needed basis when CoPP <20 mmHg. The first two vertical lines represent the first and second epinephrine doses and the third vertical line represents the vasopressin dose. The one minute of data following each epinephrine dose and the two minutes of data following the vasopressin dose are depicted. The dashed, horizontal line depicts the CoPP goal of 20 mmHg.