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Physiologic effect of repeated adrenaline (epinephrine) doses during cardiopulmonary resuscitation in the cath lab setting: A randomised porcine study

      Abstract

      Background

      This porcine study was designed to explore the effects of repetitive intravenous adrenaline doses on physiologic parameters during CPR.

      Methods

      Thirty-six adult pigs were randomised to four injections of: adrenaline 0.02 mg (kg dose)−1, adrenaline 0.03 mg (kg dose)−1 or saline control. The effect on systolic, diastolic and mean arterial blood pressure, cerebral perfusion pressure (CePP), end tidal carbon dioxide (ETCO2), arterial oxygen saturation via pulse oximetry (SpO2), cerebral tissue oximetry (SctO2), were analysed immediately prior to each injection and at peak arterial systolic pressure and arterial blood gases were analysed at baseline and after 15 min.

      Result

      In the group given 0.02 mg (kg dose)−1, there were increases in all arterial blood pressures at all 4 pressure peaks but CePP only increased significantly after peak 1. A decrease in ETCO2 following peak 1 and 2 was observed. SctO2 and SpO2 were lowered following injection 2 and beyond. In the group given a 0.03 mg (kg dose)−1, all ABP's increased at the first 4 pressure peaks but CePP only following 3 pressure peaks. Lower ETCO2, SctO2 and SpO2 were seen at peak 1 and beyond. In the two adrenaline groups, pH and Base Excess were lower and lactate levels higher compared to baseline as well as compared to the control.

      Conclusion

      Repetitive intravenous adrenaline doses increased ABP's and to some extent also CePP, but significantly decreased organ and brain perfusion.
      The institutional protocol number: Malmö/Lund Committee for Animal Experiment Ethics, approval reference number: M 192-10.

      Keywords

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      References

        • Redding J.S.
        • Pearson J.W.
        Resuscitation from asphyxia.
        JAMA. 1962; 182: 283-286
        • Nolan J.P.
        • Hazinski M.F.
        • Billi
        • et al.
        Part 1: executive summary: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations.
        Resuscitation. 2010; 81: e1-e25
        • Morrison L.J.
        • Deakin C.D.
        • Morley P.T.
        • et al.
        Part 8: advanced life support: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations.
        Circulation. 2010; 122: S345-S442
        • Wagner H.
        • Rundgren M.
        • Madsen Hardig B.
        • et al.
        A structured approach for treatment of prolonged cardiac arrest cases in the coronary catheterization laboratory using mechanical chest compressions.
        Int J Cardiovasc Res. 2013; 2: 1-7
        • Paradis N.A.
        • Martin G.B.
        • Rivers E.P.
        • et al.
        Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation.
        JAMA. 1990; 263: 1106-1113
        • Niemann J.
        • Criley J.M.
        • Rosborough J.P.
        • Niskanen R.A.
        • Alferness C.
        Predictive indices of successful cardiac resuscitation after prolonged arrest and experimental cardiopulmonary resuscitation.
        Ann Emerg Med. 1985; 14: 521-528
        • Kern K.B.
        • Ewy G.A.
        • Voorhees W.D.
        • Babbs C.F.
        • Tacker W.A.
        Myocardial perfusion pressure: a predictor of 24-h survival during prolonged cardiac arrest in dogs.
        Resuscitation. 1988; 16: 241-250
        • Reynolds J.C.
        • Salcido D.D.
        • Menegazzi J.J.
        Coronary perfusion pressure and return of spontaneous circulation after prolonged cardiac arrest.
        Prehosp Emerg Care. 2010; 14: 78-84
        • Marn-Pernat A.
        • Weil M.H.
        • Tang W.
        • Pernat A.
        • Bisera J.
        Optimizing timing of ventricular defibrillation.
        Crit Care Med. 2001; 29: 2360-2365
        • Gueugniaud P.Y.
        • Mols P.
        • Goldstein P.
        • et al.
        • European Epinephrine Study Group
        A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital.
        N Engl J Med. 1998; 339: 1595-1601
        • Mukoyama T.
        • Kinoshita K.
        • Nagao K.
        • Tanjoh K.
        Reduced effectiveness of vasopressin in repeated doses for patients undergoing prolonged cardiopulmonary resuscitation.
        Resuscitation. 2009; 80: 755-761
        • Olasveengen T.M.
        • Sunde K.
        • Brunborg C.
        • Thowsen J.
        • Steen P.A.
        • Wik L.
        Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial.
        JAMA. 2009; 302: 2222-2229
        • Jacobs I.G.
        • Finn J.C.
        • Jelinek G.A.
        • Oxer H.F.
        • Thompson P.L.
        Effect of adrenaline on survival in out-of-hospital cardiac arrest: a randomised double-blind placebo-controlled trial.
        Resuscitation. 2011; 82: 1138-1144
        • Behringer W.
        • Kittler H.
        • Sterz F.
        • et al.
        Cumulative epinephrine dose during cardiopulmonary resuscitation and neurologic outcome.
        Ann Intern Med. 1998; 129: 450-456
        • Wagner H.
        • Gotberg M.
        • Madsen Hardig B.
        • et al.
        Repeated epinephrine doses during prolonged cardiopulmonary resuscitation have limited effects on myocardial blood flow: a randomized porcine study.
        BMC Cardiovasc Disord. 2014; 14: 199
        • Ristagno G.
        • Sun S.
        • Tang W.
        • Castillo C.
        • Weil M.H.
        Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation.
        Crit Care Med. 2007; 35: 2145-2149
        • Ristagno G.
        • Tang W.
        • Huang L.
        • et al.
        Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation.
        Crit Care Med. 2009; 37: 1408-1415
        • Prengel A.W.
        • Lindner K.H.
        • Keller A.
        Cerebral oxygenation during cardiopulmonary resuscitation with epinephrine and vasopressin in pigs.
        Stroke. 1996; 27: 1241-1248
        • 19.Burnett A.M.
        • Segal N.
        • Salzman J.G.
        • McKnite M.S.
        • Frascone R.J.
        Potential negative effects of epinephrine on carotid blood flow and ETCO2 during active compression-decompression CPR utilizing an impedance threshold device.
        Resuscitation. 2012; 83: 1021-1024
        • Tank A.W.
        • Lee Wong D.
        Peripheral and central effects of circulating catecholamines.
        Compr Physiol. 2015; 5: 1-15
        • Wagner H.
        • Terkelsen C.J.
        • Friberg H.
        • et al.
        Cardiac arrest in the catheterisation laboratory: a 5-year experience of using mechanical chest compressions to facilitate PCI during prolonged resuscitation efforts.
        Resuscitation. 2010; 81: 383-387
        • Pytte M.
        • Kramer-Johansen J.
        • Eilevstjonn J.
        • et al.
        Haemodynamic effects of adrenaline (epinephrine) depend on chest compression quality during cardiopulmonary resuscitation in pigs.
        Resuscitation. 2006; 71: 369-378
        • Chen M.
        • Lu R.
        • Xie L.
        • Zheng J.
        • Song F.
        What is the optimal dose of epinephrine during cardiopulmonary resuscitation in a rat model?.
        Am J Emerg Med. 2010; 28: 284-290
        • Johansson J.
        • Gedeborg R.
        • Basu S.
        • Rubertsson S.
        Increased cortical cerebral blood flow by continuous infusion of adrenaline (epinephrine) during experimental cardiopulmonary resuscitation.
        Resuscitation. 2003; 57: 299-307
        • Parnia S.
        • Nasir A.
        • Ahn A.
        • et al.
        A feasibility study of cerebral oximetry during in-hospital mechanical and manual cardiopulmonary resuscitation.
        Crit Care Med. 2013; 42: 930-933
        • Ito N.
        • Nanto S.
        • Nagao K.
        • Hatanaka T.
        • Kai T.
        Regional cerebral oxygen saturation predicts poor neurological outcome in patients with out-of-hospital cardiac arrest.
        Resuscitation. 2010; 81: 1736-1737
        • Grmec S.
        • Klemen P.
        Does the end-tidal carbon dioxide (EtCO2) concentration have prognostic value during out-of-hospital cardiac arrest?.
        Eur J Emerg Med. 2001; 8: 263-269
        • Bendixen H.H.
        • Laver M.B.
        • Flacke W.E.
        Influence of respiratory acidosis on circulatory effect of epinephrine in dogs.
        Circ Res. 1963; 13: 64-70
        • Blumenthal J.S.
        • Blumenthal M.N.
        • Brown E.B.
        • Campbell G.S.
        • Prasad A.
        Effect of changes in arterial pH on the action of adrenalin in acute adrenaline-fast asthmatics.
        Chest. 1961; 39: 516-522
        • Kaji A.H.
        • Hanif A.M.
        • Bosson N.
        • Ostermayer D.
        • Niemann J.T.
        Predictors of neurologic outcome in patients resuscitated from out-of-hospital cardiac arrest using classification and regression tree analysis.
        Am J Cardiol. 2014; 114: 1024-1028
        • Lee D.H.
        • Chob I.S.
        • Lee S.H.
        • et al.
        The Korean Hypothermia Network Investigators: correlation between initial serum levels of lactate after return of spontaneous circulation and survival and neurological outcomes in patients who undergo therapeutic hypothermia after cardiac arrest.
        Resuscitation. 2015; 88: 143-149
        • Grip J.
        • Jakobsson T.
        • Hebert C.
        • et al.
        Lactate kinetics and mitochondrial respiration in skeletal muscle of healthy humans under influence of adrenaline.
        Clin Sci (Lond). Aug 2015; 129: 375-384
        • Olasveengen T.M.
        • Wik L.
        • Sunde K.
        • Steen P.A.
        post hoc analysis of a randomized clinical trial.
        Resuscitation. 2012; 83: 327-332
        • Donnino M.W.
        • Salciccioli J.D.
        • Howell M.D.
        • et al.
        Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry.
        BMJ. 2014; 348: g3028
        • Nordseth T.
        • Olasveengen T.M.
        • Kvaloy J.T.
        • Wik L.
        • Steen P.A.
        • Skogvoll E.
        Dynamic effects of adrenaline (epinephrine) in out-of-hospital cardiac arrest with initial pulseless electrical activity (PEA).
        Resuscitation. 2012; 83: 946-952
        • Warren S.A.
        • Huszti E.
        • Bradley S.M.
        • et al.
        Adrenaline (epinephrine) dosing period and survival after in-hospital cardiac arrest: a retrospective review of prospectively collected data.
        Resuscitation. 2014; 85: 350-358