Adrenaline
Resuscitation
V-GRADE
This area explains how the V-Grade displayed for this monograph was calculated and, therefore, the robustness of these recommendations.
Adrenaline Recommendations
Resuscitation
Emergency CPCR
0.01 mg/kg, IV/IO, every other cycle of basic life support (BLS), for a maximum of four administrations.
Ongoing CPCR
Deliver the previously calculated dose as an IV or IO bolus every other cycle of basic life support (BLS), i.e. every 3–5 minutes. If adrenaline administration alternates with vasopressin, we recommend a maximum of two administrations.
Indications for Administration
Adrenaline (Epinephrine) administration is recommended during cardiopulmonary cerebral resuscitation (CPCR), where the return of spontaneous circulation (ROSC) has not occurred within the initial two basic life support (BLS) cycles and after administering any available anaesthetic reversal agent if cardiopulmonary arrest (CPA) occurs during anaesthesia.
CPCR Reporting
We recommend that the CPCR team use the RECOVER-Initiative-CPR-Reporting-Sheet.
Basic Life Support (BLS)
Initiate BLS as soon as CPA is suspected or confirmed.
One BLS cycle is 2 minutes of uninterrupted compression/ventilation (Fletcher et al., 2012).
1 Chest Compressions
Chest compressions should be initiated immediately on recognition of CPA.
Position: Cardiac compressions using a one-hand technique, with the compressor’s fingers wrapped around the sternum at the level of the heart to generate a circumferential cardiac compression, are effective (Buckley et al., 2011; Hall, 2023).
Technique: In lateral recumbency, the chest should be compressed one-third to half its width at 100-150 compressions/min (Fletcher et al., 2012; Hopper et al., 2012).
2 Ventilation Support
Patients who require CPCR due to general anaesthesia events are likely already intubated. We recommend that the CPCR team intubate all animals without airway support or move to alternative airway support, wherever possible, using the following guidelines.
Ventilatory support is provided after the initiation of chest compressions and aims to reduce both hypoxia and hypercapnia. Initially, for a non-intubated patient, the airway is rapidly opened through gentle traction on the tongue using blunt forceps. To facilitate chest compression, tongue traction is done with the patient in lateral recumbency with the head and neck extended. If available, provide flow by oxygen.
RECOVER guidelines recommend early intubation and ventilation in dogs and cats because of the ease of intubation. However, rabbits are more challenging, and the CRCP team must balance the time taken to intubate a rabbit with the availability of alternative methods of airway support such as V-Gel tubes, suitably fitted face masks and tracheostomy. We recommend that the team take at most 60 seconds to intubate the rabbit before abandoning the technique if an alternative method of airway support is available.
Intubation: The clinician should use the technique with which they are most confident and familiar and allow up to 60 seconds for intubation with the tongue extended and flow of oxygen where available. Various intubation techniques are effective (blind, endoscopic, otoscopic. laryngoscopic). Intubation of animals in lateral recumbency avoids interrupting chest compressions. Where available, capnography confirms correct tube placement.
Masks: Tight-fitting face masks also provide practical respiratory support and reduce any delay in starting chest compressions (Buckley et al., 2011; Hall, 2023).
V-Gel: Current evidence suggests an appropriately placed V-gel tube is as effective as standard intubation (Bruce and Brennan, 2023; Comolli et al., 2020; Engbers et al., 2017; Fusco et al., 2021; Uzun et al., 2015). Where available, capnography confirms correct tube placement.
Tracheostomy: Given the ease with which airway support is achieved through the strategic airway and tongue extension in lateral recumbency, tracheostomy is rarely indicated, as they leave any recovered patient severely traumatised and hard to manage post-resuscitation (Benito et al., 2021; Dion et al., 2018).
3 Compression-to-ventilation Ratio (C-V Ratio)
The optimal C-V ratio for rabbits undergoing CPCR has yet to be determined. No rabbit studies have addressed this issue.
Intubated patients: We recommend ten breaths/min ventilation rate with a 10 mL/kg tidal volume and a short inspiratory time of 1-second for intubated rabbit patients (Fletcher et al., 2012; Hopper et al., 2012).
Non-intubated patients: We recommend 30 chest compressions at a rate of 100–120/min, followed by two breaths delivered quickly via mouth to snout or ambu bag (Fletcher et al., 2012; Hopper et al., 2012).
4 Timing of CPR Cycles
No rabbit studies have addressed this issue.
We recommend 2 minutes of uninterrupted chest compressions before checking the rhythm as this timing is associated with increased survival compared to more frequent pauses in human CPR (Hopper et al., 2012).
Advanced Life Support (ALS)
After initiating BLS to support systemic circulation, a functional airway, and ventilation, veterinary team members not actively involved in chest compressions or ventilation support should help provide ALS, which includes:
1 Vascular and Intraosseous Access
Patients who require CPCR due to general anaesthesia are likely to have vascular access already. We recommended that the CPCR team cannulate all animals without vascular access.
Suitable sites include the marginal ear vein, cephalic, saphenous, or jugular vein to allow further drug or fluid administration (Brown, 1997; Graham and Mader, 2012; Harcourt-Brown, 2002; Huynh et al., 2016; Paul-Murphy, 2007; Paul-Murphy and Ramer, 1998; Quesenberry, 2021; Varga-Smith, 2022). An intraosseous route can be employed where IV access is unavailable or unachievable (Buckley et al., 2011; Huynh et al., 2016; Lichtenberger, 2007; Onuma et al., 2017; Paul-Murphy, 2007; Paul-Murphy and Ramer, 1998).
IV Access: Our recommendation is the marginal ear vein cephalic or saphenous veins to allow effective cannula stabilisation
IO Access: Our recommendation is the proximal humerus, tibial crest or proximal femur
2 Medications
Anaesthetic/Sedative Reversal Agents: Patients experiencing pulseless electrical activity due to general anaesthesia should be administered reversal agents where appropriate, with welfare-based consideration of an abrupt return to consciousness or potential loss of analgesia. This is normally done one BLS cycle before vasopressor administration.
Atipamezole: Administration reverses the sedative effects of alpha2-adrenoreceptor Agonist Agents, typically Medetomidine and Dexmedetomidine components of multimodal anaesthesia protocols.
Flumazenil: Administration reverses the benzodiazepine components of multimodal anaesthesia protocols.
Naloxone: Administration reverses full and partial opiate agonists
Other Opiate Reversal Options: Reversal of full Mu opiate agonists can also be achieved using partial agonists such as Buprenorphine or Butorphanol, and this may leave some residual analgesia.
Vasopressor Agents: Vasopressors such as Adrenaline (Epinephrine) and Vasopressin are ideal for ALS.
Adrenaline (Epinephrine): Adrenaline is a nonspecific catecholamine adrenergic agonist with beneficial ⍺1 vasopressor activity during CPR. Adrenaline also has β1 adrenergic activity, the inotropic and chronotropic effects of which are likely less crucial and potentially harmful due to increased myocardial oxygen demand, exacerbating myocardial ischemia and predisposing to arrhythmias once the return of spontaneous circulation (ROSC) is achieved. ⍺2-agonist effects increase peripheral arteriolar vasoconstriction and override β2-agonist–induced hypotension. This increases vascular resistance and arterial blood pressure, which shunts blood to the brain, heart, and lungs (Plunkett and McMichael, 2008).
Adrenaline (Epinephrine): See dosing advice above.
Limit adrenaline use to what is necessary to achieve ROSC (Bassiakou et al., 2009; Fletcher et al., 2012; Maddison, 2008; Plumb, 2024).
Vasopressin: Vasopressin is a potent vasoconstricting agent during CPCR. However, it is not universally available, so it may not be a clinical option in all countries where rabbits are treated. Vasopressin may increase myocardial perfusion and reduce myocardial oxygen consumption compared to adrenaline. Vasopressor effects of Vasopressin are mediated through V1 receptors located on peripheral vascular smooth muscle, a mechanism independent of the ⍺1 effects of epinephrine (Fletcher et al., 2012). Cat and dog RECOVER protocols discuss alternating the use of vasopressin and adrenaline. The benefits of vasopressin use with or without adrenaline during rabbit CPCR remain unknown. However, one study suggests that primary adrenaline use remains superior during reperfusion as adrenaline counteracted cerebral vasoconstriction better than vasopressin (Kondo et al., 2022).
Vasopressin: 0.8 U/kg, IV, alternating with Epinephrine every other BLS cycle (Fletcher et al., 2012).
Anticholinergic Agents: Evidence supporting anticholinergic agents, e.g. Atropine or Glycopyrrolate during CPR, is limited. During rabbit CPCR, anticholinergic agents are considered an additional drug rather than a sole intervention. Rabbits with high vagal tone (e.g., severe gastrointestinal disease or respiratory distress) associated with cardiac arrest may benefit from anticholinergic drugs. There is no evidence that anticholinergic agents are harmful in rabbit CPCR, but no high-quality studies support their use in rabbits, dogs or cats (Rozanski et al., 2012).
Atropine: 0.1-0.5 mg/kg, IM/IV, q10-15 mins (PRN); Endogenous atropinase is present in as many as 60% of rabbits and limits clinical use to emergency management of severe bradycardia (Harrison et al., 2006; Liebenberg & Linn, 1980; Olson et al., 1994).
Glycopyrrolate: 0.01-0.1 mg/kg, SC/IM/IV/IO/IT q60 mins (PRN) (Olson et al., 1994)
3 Monitoring
Monitoring is part of advanced life support and post-CRCR care. Monitoring equipment will vary with the clinical setting. BLS cycles are set at two minutes, the onset of CPCR should be recorded, and cycle time should be monitored per RECOVER guidelines using the RECOVER Initiative CPR Reporting Sheet every 2 minutes.
AS ROSC is the primary aim, the patient must be carefully monitored between BLS cycles for ROSC. RECOVER suggests that compressions should be rested for <10 seconds during such monitoring (Fletcher et al., 2012).
Vital Signs: Assessing tissue perfusion characteristics such as CRT, pulse rate and character, respiratory rate, and heart rate between basic life support cycles are helpful manual monitoring parameters (Fletcher et al., 2012).
Capnography: End-tidal carbon dioxide (EtCO2) monitoring indicates that chest compressions achieve peripheral perfusion or ROSC (Fletcher et al., 2012).
Doppler: After initiating cardiac compressions, pulse detection using Doppler indicates that chest compressions achieve peripheral perfusion (Schnellbacher et al., 2012; Barter and Epstein, 2014).
Pulse Oximetry: After initiating cardiac compressions, pulse detection using oximetry indicates that chest compressions achieve peripheral perfusion (Schnellbacher et al., 2012; Onuma et al., 2017)
ECG: ECG analysis during CPR may be helpful. However, the possibility of pulseless electrical activity (PEA) leaves ECG inappropriate as a sole diagnostic tool.
Post-Resuscitation Monitoring: Post-resuscitation monitoring should be sufficient to detect any impending reoccurrence of CPA (Fletcher et al., 2012).
4 Additional Nursing Support
Thermal Support: Hypothermia leads to altered coagulation, organ dysfunction, and electrolyte and acid-base abnormalities (Di Girolamo et al., 2016; Huynh et al., 2016; Pachtinger, 2013).
Fluid Support: Patients in cardiogenic, distributive, or septic shock require appropriate circulatory support (Lichtenberger, 2004 and 2007).
Alternative Protocols
Nonresponder Anaesthesia Associated CPCR
Salvage CPCR: If four doses of vasopressor agents have been administered without ROSC (i.e. 8 BSL cycles), a single high salvage dose of Adrenaline (>0.1 mg/kg IV) may be considered alongside BLS, provided no other beneficial therapeutic options are apparent (Fletcher et al., 2012).
Therapeutics
Our recommendations for rabbit CPCR (cardiopulmonary cerebral resuscitation) follow RECOVER guidelines for reversing cardiopulmonary arrest (CPA) in cats and dogs using the RECOVER-Initiative-CPR-Reporting-Sheet.
Administration of Adrenaline (Epinephrine) is one component of advanced life support (ALS) provided after basic life support (BLS) during rabbit CPCR.
Administration of Adrenaline is not a substitute for providing BLS components [recognition of CPA, chest compressions, secure airway, and ventilatory support] (Hopper et al., 2012; Hall, 2023).
We recommend administering low-dose adrenaline during rabbit CPCR, but high-dose administration is acceptable if ongoing resuscitation efforts have been unsuccessful (Costello, 2004).
CPCR is an emergency procedure; team members not actively involved in BLS should help provide appropriate ALS as described in our dosing section.
Evidence-Base and Efficacy Profile
The efficacy profile for Adrenaline use during rabbit CPCR is limited. The efficacy of our adrenaline protocol in spontaneous CPA is unknown. This is because CPA occurs in a wide range of extreme situations, and excessive or inappropriate adrenaline administration may harm (Downing and Chen, 1985). Adrenaline administration may affect patient outcomes, but BLS is still the most critical aspect of resuscitation and patient survival (Long and Koyfman, 2017).
Uniform reporting and efficacy evaluations are only possible with consensus on optimum CPCR protocol responses, and the collection of such data is not standardised. Limited evidence suggests a CPCR benefit (Buckley et al., 2011; Harvey et al., 2010; Kohlhauer et al., 2014; Onuma et al., 2017).
VCI recommends that clinicians consider multimodal use if the criteria given earlier within this monograph appear to have been met (e.g., the rabbit has received a reversible anaesthetic agent).
Anaesthetic-associated PEA-CPA: We recommended CPCR in all ASA 1 and 2 rabbits with anaesthetic-associated PEA-CPA. CPCR is likely effective if undertaken promptly in line with the advice here (Buckley et al., 2011; Harvey et al., 2010; Kii et al., 2004; Kohlhauer et al., 2014; Onuma et al., 2017)
Spontaneous/Non-anaesthetic-related PEA CPA: We recommended clinicians consider CPCR adrenaline use case-by-case.
Clinicians must assess the significance and severity of comorbidities before deciding upon the resuscitation endpoint. In situations where severe chronic comorbidities are present, resuscitation is both unwise and unable to return an adequate quality of life.
Sole Use
The sole use of Adrenaline alongside BLS suits CPCR well, provided no reversible anaesthetic agents have been administered. Agent reversal should be performed alongside vasopressor administration and BLS in this case.
Multimodal Use
During appropriate rabbit CPCR, various ALS agents should be administered alongside Adrenaline if the following indication criteria are met:
Anaesthetic Reversal Agents: During anaesthetic-derived CPA, reversible agents contributing to the patient's demise should be reversed, as covered in our dosing recommendations and under the relevant active substances within this database.
Vasopressor agents: Vasopressin can be alternated with adrenaline (Epinephrine); every other cycle is an option.
Anticholinergic Agents: Animals with high vagal tone and subsequent bradycardia/asystole (e.g., gastrointestinal pain or prolonged dyspnoea) may benefit from the administration of atropine or glycopyrrolate (Rozanski et al., 2012).
Treatment Goals
ROSC: Adrenaline administration aims to recover spontaneous circulation with minimum damage to the patient, i.e., to combine use with optimum BLS, minimum trauma, and to limit excessive administration of adrenaline.
Treatment Endpoints
ROSC: Adrenaline administration ceases when ROSC has been achieved or the patient is declared deceased. Avoid additional adrenaline after ROSC is achieved.
Evidence
Bibliography
Barter, L.S., Epstein, S.E., 2014. Comparison of Doppler, oscillometric, auricular and carotid arterial blood pressure measurements in isoflurane anesthetized New Zealand white rabbits. Veterinary Anaesthesia and Analgesia 41, 393–397. https://doi.org/10.1111/vaa.12131
Bassiakou, E., Xanthos, T., Papadimitriou, L., 2009. The potential beneficial effects of beta adrenergic blockade in the treatment of ventricular fibrillation. European Journal of Pharmacology 616, 1–6. https://doi.org/10.1016/j.ejphar.2009.06.019
Benito, S., Hadley, S., Camprubí-Camprubí, M., Sanchez-de-Toledo, J., 2021. Blind Endotracheal Intubation in Neonatal Rabbits. J Vis Exp. https://doi.org/10.3791/61874
Booth, D., 2011. Small Animal Clinical Pharmacology and Therapeutics - 2nd Edition [WWW Document]. URL https://shop.elsevier.com/books/small-animal-clinical-pharmacology-and-therapeutics/boothe/978-0-7216-0555-5 (accessed 1.24.24).
Brown, S.A., 1997. Clinical techniques in rabbits. Seminars in Avian and Exotic Pet Medicine, Clinical Techniques 6, 86–95. https://doi.org/10.1016/S1055-937X(97)80015-1
Bruce, H., Brennan, M., 2023. Does an endotracheal tube or a v-gel result in better controlled ventilation in anaesthetised rabbits? Vet Rec 193, 326–327. https://doi.org/10.1002/vetr.3585
Buckley, G.J., DeCubellis, J., Sharp, C.R., Rozanski, E.A., 2011. Cardiopulmonary Resuscitation in Hospitalized Rabbits: 15 cases. Journal of Exotic Pet Medicine, Zoonotic Diseases 20, 46–50. https://doi.org/10.1053/j.jepm.2010.11.010
Comolli, J., Schnellbacher, R., Beaufrere, H., Blas-Machado, U., Quandt, J., Mayer, J., Divers, S.J., 2020. Comparison of endoscopic endotracheal intubation and the v-gel supraglottic airway device for spontaneously ventilating New Zealand white rabbits undergoing ovariohysterectomy. Vet Rec 187, e84. https://doi.org/10.1136/vr.105746
Costello, M.F., 2004. Principles of cardiopulmonary cerebral resuscitation in special species. Seminars in Avian and Exotic Pet Medicine, Emergency Medicine 13, 132–141. https://doi.org/10.1053/j.saep.2004.03.003
DeWitt, E.S., Black, K.J., Thiagarajan, R.R., DiNardo, J.A., Colan, S.D., McGowan, F.X., Kheir, J.N., 2016. Effects of commonly used inotropes on myocardial function and oxygen consumption under constant ventricular loading conditions. J Appl Physiol (1985) 121, 7–14. https://doi.org/10.1152/japplphysiol.00058.2016
Di Girolamo, N., Toth, G., Selleri, P., 2016. Prognostic value of rectal temperature at hospital admission in client-owned rabbits. J. Am. Vet. Med. Assoc. 248, 288–297. https://doi.org/10.2460/javma.248.3.288
Dion, G.R., Benedict, P.A., Amin, M.R., Branski, R.C., 2018. Morbidity and mortality associated with preclinical tracheostomy models. Laryngoscope 128, E68–E71. https://doi.org/10.1002/lary.26878
Downing, S.E., Chen, V., 1985. Myocardial injury following endogenous catecholamine release in rabbits. Journal of Molecular and Cellular Cardiology 17, 377–387. https://doi.org/10.1016/S0022-2828(85)80137-1
EMC, 2024a. Dilute Adrenaline (Epinephrine) Injection 1:10,000 (ampoules) - Summary of Product Characteristics (SmPC) - (emc) [WWW Document]. URL https://www.medicines.org.uk/emc/product/3675/smpc (accessed 1.23.24).
EMC, 2024b. Adrenaline Injection BP 1/1000 (1mg/1ml) - Summary of Product Characteristics (SmPC) - (emc) [WWW Document]. URL https://www.medicines.org.uk/emc/product/6595/smpc (accessed 1.23.24).
EMC, 2024c. Adrenaline 1 mg/10 ml (1:10,000), solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC) - (emc) [WWW Document]. URL https://www.medicines.org.uk/emc/product/2024/smpc (accessed 1.23.24).
EMC, 2024d. Adrenaline (Epinephrine) Injection BP 1 in 1000 - Summary of Product Characteristics (SmPC) - (emc) [WWW Document]. URL https://www.medicines.org.uk/emc/product/6284/smpc (accessed 1.23.24).
EMC, 2024e. Adrenaline (Epinephrine) 1mg/ml (1:1000) solution for injection (ampoule) - Summary of Product Characteristics (SmPC) - (emc) [WWW Document]. URL https://www.medicines.org.uk/emc/product/3673/smpc (accessed 1.23.24).
Engbers, S., Larkin, A., Rousset, N., Prebble, M., Jonnalagadda, M., Knight, C.G., Pang, D.S.J., 2017. Comparison of a Supraglottic Airway Device (v-gel®) with Blind Orotracheal Intubation in Rabbits. Front Vet Sci 4, 49. https://doi.org/10.3389/fvets.2017.00049
Farzam, K., Kidron, A., Lakhkar, A.D., 2024. Adrenergic Drugs, in: StatPearls. StatPearls Publishing, Treasure Island (FL).
Fletcher, D.J., Boller, M., Brainard, B.M., Haskins, S.C., Hopper, K., McMichael, M.A., Rozanski, E.A., Rush, J.E., Smarick, S.D., American College of Veterinary Medicine, Veterinary Emergency and Critical Care Society, 2012. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 7: Clinical guidelines. J Vet Emerg Crit Care (San Antonio) 22 Suppl 1, S102-131. https://doi.org/10.1111/j.1476-4431.2012.00757.x
Fusco, A., Douglas, H., Barba, A., Hopster, K., Stefanovski, D., Sinder, B., Cahill, P.J., Snyder, B., Schaer, T.P., 2021. V-Gel® Guided Endotracheal Intubation in Rabbits. Front Vet Sci 8, 684624. https://doi.org/10.3389/fvets.2021.684624
Graham, J., Mader, D.R., 2012. Chapter 13 - Basic Approach to Veterinary Care, in: Quesenberry, K.E., Carpenter, J.W. (Eds.), Ferrets, Rabbits, and Rodents (Third Edition). W.B. Saunders, Saint Louis, pp. 174–182. https://doi.org/10.1016/B978-1-4160-6621-7.00013-0
Hall, N.H., 2023. Cerebro-Cardiopulmonary Resuscitation and Postarrest Care in Exotic Animal Critical Care. Veterinary Clinics of North America: Exotic Animal Practice 26, 737–750. https://doi.org/10.1016/j.cvex.2023.05.010
Harcourt-Brown, F., 2002. The rabbit consultation and clinical techniques. Textbook of Rabbit Medicine 52–93. https://doi.org/10.1016/B978-075064002-2.50006-0
Harrison, P.K., Tattersall, J.E.H., Gosden, E., 2006. The presence of atropinesterase activity in animal plasma. Naunyn Schmiedebergs Arch Pharmacol 373, 230–236. https://doi.org/10.1007/s00210-006-0054-5
Harvey, M., Cave, G., Prince, G., Lahner, D., 2010. Epinephrine injection in lipid-based resuscitation from bupivacaine-induced cardiac arrest: transient circulatory return in rabbits. Anesth Analg 111, 791–796. https://doi.org/10.1213/ANE.0b013e3181e66050
Hopper, K., Epstein, S.E., Fletcher, D.J., Boller, M., Authors, the R.B.L.S.D.W., 2012. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 3: Basic life support. Journal of Veterinary Emergency and Critical Care 22, S26–S43. https://doi.org/10.1111/j.1476-4431.2012.00753.x
Huynh, M., Boyeaux, A., Pignon, C., 2016. Assessment and Care of the Critically Ill Rabbit. Vet Clin North Am Exot Anim Pract 19, 379–409. https://doi.org/10.1016/j.cvex.2016.01.011
Kii, N., Adachi, N., Yorozuya, T., Nagaro, T., Arai, T., 2004. Suppression of endogenous catecholamine release by anesthetics during cardiopulmonary resuscitation in the rabbit. Can J Anaesth 51, 404–405. https://doi.org/10.1007/BF03018255
Kohlhauer, M., Darbera, L., Lidouren, F., Chenoune, M., Ghaleh, B., Vivien, B., Carli, P., Dabire, H., Berdeaux, A., Tissier, R., 2014. Comparative effect of hypothermia and adrenaline during cardiopulmonary resuscitation in rabbits. Shock 41, 154–158. https://doi.org/10.1097/SHK.0000000000000083
Kondo, D., Asano, N., Ishiyama, T., Shintani, N., Matsukawa, T., 2022. Effects of adrenaline and vasopressin on cerebral microcirculation at baseline and during global brain ischemia and reperfusion in rabbits. BMC Anesthesiol 22, 380. https://doi.org/10.1186/s12871-022-01926-9
Lichtenberger, M., 2007. Shock and Cardiopulmonary-Cerebral Resuscitation in Small Mammals and Birds. Veterinary Clinics of North America: Exotic Animal Practice, Emergency and Critical Care 10, 275–291. https://doi.org/10.1016/j.cvex.2007.02.001
Lichtenberger, M., 2004. Principles of shock and fluid therapy in special species. Seminars in Avian and Exotic Pet Medicine, Emergency Medicine 13, 142–153. https://doi.org/10.1053/j.saep.2004.03.004
Liebenberg, S.P., Linn, J.M., 1980. Seasonal and sexual influences on rabbit atropinesterase. Lab Anim 14, 297–300. https://doi.org/10.1258/002367780781071012
Long, B., Koyfman, A., 2017. Emergency Medicine Myths: Epinephrine in Cardiac Arrest. J Emerg Med 52, 809–814. https://doi.org/10.1016/j.jemermed.2016.12.020
Maddison, G., 2008. Small Animal Clinical Pharmacology E-Book: 2nd edition | Edited by Jill E. Maddison | ISBN: 9780702037252 [WWW Document]. Elsevier Asia Bookstore. URL https://www.asia.elsevierhealth.com/small-animal-clinical-pharmacology-e-book-9780702037252.html (accessed 1.23.24).
Olson, M.E., Vizzutti, D., Morck, D.W., Cox, A.K., 1994. The parasympatholytic effects of atropine sulfate and glycopyrrolate in rats and rabbits. Can J Vet Res 58, 254–258.
Onuma, M., KONDO, H., ONO, S., MURAKAMI, A., HARADA, T., SANO, T., 2017. Retrospective investigation of cardiopulmonary resuscitation outcome in 146 exotic animals. J Vet Med Sci 79, 1611–1614. https://doi.org/10.1292/jvms.16-0360
Oyebola, P.D.D.O., 2011. Effect of adrenaline on glucose uptake in the rabbit small intestine. African Journal of Medicine and Medical Sciences 40, 225–233.
Pachtinger, G., 2013. Monitoring of the Emergent Small Animal Patient. Veterinary Clinics: Small Animal Practice 43, 705–720. https://doi.org/10.1016/j.cvsm.2013.03.014
Paul-Murphy, J., 2007. Critical Care of the Rabbit. Veterinary Clinics of North America: Exotic Animal Practice, Emergency and Critical Care 10, 437–461. https://doi.org/10.1016/j.cvex.2007.03.002
Paul-Murphy, J., Ramer, J.C., 1998. Urgent care of the pet rabbit. Vet Clin North Am Exot Anim Pract 1, 127–152, vi–vii. https://doi.org/10.1016/s1094-9194(17)30158-5
Plumb, 2024. Epinephrine [WWW Document]. URL https://app.plumbs.com/drug/yTTIqZPq6HPROD?source=search&searchQuery=epineph§ion=doses (accessed 1.23.24).
Plunkett, S.J., McMichael, M., 2008. Cardiopulmonary resuscitation in small animal medicine: an update. J Vet Intern Med 22, 9–25. https://doi.org/10.1111/j.1939-1676.2007.0033.x
PubChem, 2024. Epinephrine [WWW Document]. URL https://pubchem.ncbi.nlm.nih.gov/compound/5816 (accessed 2.24.24).
Quesenberry, K.E. (Ed.), 2021. Ferrets, rabbits, and rodents: clinical medicine and surgery, Fourth edition. ed. Elsevier, St. Louis, Missouri.
Rozanski, E.A., Rush, J.E., Buckley, G.J., Fletcher, D.J., Boller, M., RECOVER Advanced Life Support Domain Worksheet Authors, 2012. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 4: Advanced life support. J Vet Emerg Crit Care (San Antonio) 22 Suppl 1, S44-64. https://doi.org/10.1111/j.1476-4431.2012.00755.x
Schnellbacher, R., Olson, E.E., Mayer, J., 2012. Emergency Presentations Associated with Cardiovascular Disease in Exotic Herbivores. Journal of Exotic Pet Medicine, Emergency Presentation of Exotic Mammal Herbivores 21, 316–327. https://doi.org/10.1053/j.jepm.2012.09.007
Towell, M.E., Lysak, I., Layne, E.C., Sayler, D., Bessman, S.P., 1981. The effect of epinephrine on blood and tissue PO2 in the rabbit. Circ Shock 8, 123–130.
Uzun, M., Kiraz, H.A., Ovali, M.A., Sahin, H., Erbas, M., Toman, H., 2015. The investigation of airway management capacity of v-gel and cobra-PLA in anaesthetised rabbits. Acta Cir Bras 30, 80–86. https://doi.org/10.1590/S0102-86502015001000011
Varga-Smith, M., 2022. Textbook of Rabbit Medicine - 9780702084034 | Elsevier Health [WWW Document]. Elsevier UK. URL https://www.uk.elsevierhealth.com/textbook-of-rabbit-medicine-9780702084034.html (accessed 1.23.24).
WHO, 2024. Adrenaline (Epinephrine) WHOCC - ATC/DDD Index [WWW Document]. URL https://www.whocc.no/atc_ddd_index/ (accessed 2.24.24).
1 Species-Specific Evidence Review
Buckley, G.J., DeCubellis, J., Sharp, C.R., Rozanski, E.A., 2011. Cardiopulmonary Resuscitation in Hospitalized Rabbits: 15 cases. Journal of Exotic Pet Medicine, Zoonotic Diseases 20, 46–50. https://doi.org/10.1053/j.jepm.2010.11.010
Harvey, M., Cave, G., Prince, G., Lahner, D., 2010. Epinephrine injection in lipid-based resuscitation from bupivacaine-induced cardiac arrest: transient circulatory return in rabbits. Anesth Analg 111, 791–796. https://doi.org/10.1213/ANE.0b013e3181e66050
Kohlhauer, M., Darbera, L., Lidouren, F., Chenoune, M., Ghaleh, B., Vivien, B., Carli, P., Dabire, H., Berdeaux, A., Tissier, R., 2014. Comparative effect of hypothermia and adrenaline during cardiopulmonary resuscitation in rabbits. Shock 41, 154–158. https://doi.org/10.1097/SHK.0000000000000083
Paul-Murphy, J., 2007. Critical Care of the Rabbit. Veterinary Clinics of North America: Exotic Animal Practice, Emergency and Critical Care 10, 437–461. https://doi.org/10.1016/j.cvex.2007.03.002
2 Condition-Specific Evidence Review
Barter, L.S., Epstein, S.E., 2014. Comparison of Doppler, oscillometric, auricular and carotid arterial blood pressure measurements in isoflurane anesthetized New Zealand white rabbits. Veterinary Anaesthesia and Analgesia 41, 393–397. https://doi.org/10.1111/vaa.12131
Bassiakou, E., Xanthos, T., Papadimitriou, L., 2009. The potential beneficial effects of beta adrenergic blockade in the treatment of ventricular fibrillation. European Journal of Pharmacology 616, 1–6. https://doi.org/10.1016/j.ejphar.2009.06.019
Buckley, G.J., DeCubellis, J., Sharp, C.R., Rozanski, E.A., 2011. Cardiopulmonary Resuscitation in Hospitalized Rabbits: 15 cases. Journal of Exotic Pet Medicine, Zoonotic Diseases 20, 46–50. https://doi.org/10.1053/j.jepm.2010.11.010
Costello, M.F., 2004. Principles of cardiopulmonary cerebral resuscitation in special species. Seminars in Avian and Exotic Pet Medicine, Emergency Medicine 13, 132–141. https://doi.org/10.1053/j.saep.2004.03.003
Di Girolamo, N., Toth, G., Selleri, P., 2016. Prognostic value of rectal temperature at hospital admission in client-owned rabbits. J. Am. Vet. Med. Assoc. 248, 288–297. https://doi.org/10.2460/javma.248.3.288
Fletcher, D.J., Boller, M., Brainard, B.M., Haskins, S.C., Hopper, K., McMichael, M.A., Rozanski, E.A., Rush, J.E., Smarick, S.D., American College of Veterinary Medicine, Veterinary Emergency and Critical Care Society, 2012. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 7: Clinical guidelines. J Vet Emerg Crit Care (San Antonio) 22 Suppl 1, S102-131. https://doi.org/10.1111/j.1476-4431.2012.00757.x
Hall, N.H., 2023. Cerebro-Cardiopulmonary Resuscitation and Postarrest Care in Exotic Animal Critical Care. Veterinary Clinics of North America: Exotic Animal Practice 26, 737–750. https://doi.org/10.1016/j.cvex.2023.05.010
Harvey, M., Cave, G., Prince, G., Lahner, D., 2010. Epinephrine injection in lipid-based resuscitation from bupivacaine-induced cardiac arrest: transient circulatory return in rabbits. Anesth Analg 111, 791–796. https://doi.org/10.1213/ANE.0b013e3181e66050
Hopper, K., Epstein, S.E., Fletcher, D.J., Boller, M., Authors, the R.B.L.S.D.W., 2012. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 3: Basic life support. Journal of Veterinary Emergency and Critical Care 22, S26–S43. https://doi.org/10.1111/j.1476-4431.2012.00753.x
Huynh, M., Boyeaux, A., Pignon, C., 2016. Assessment and Care of the Critically Ill Rabbit. Vet Clin North Am Exot Anim Pract 19, 379–409. https://doi.org/10.1016/j.cvex.2016.01.011
Kohlhauer, M., Darbera, L., Lidouren, F., Chenoune, M., Ghaleh, B., Vivien, B., Carli, P., Dabire, H., Berdeaux, A., Tissier, R., 2014. Comparative effect of hypothermia and adrenaline during cardiopulmonary resuscitation in rabbits. Shock 41, 154–158. https://doi.org/10.1097/SHK.0000000000000083
Lichtenberger, M., 2007. Shock and Cardiopulmonary-Cerebral Resuscitation in Small Mammals and Birds. Veterinary Clinics of North America: Exotic Animal Practice, Emergency and Critical Care 10, 275–291. https://doi.org/10.1016/j.cvex.2007.02.001
Lichtenberger, M., 2004. Principles of shock and fluid therapy in special species. Seminars in Avian and Exotic Pet Medicine, Emergency Medicine 13, 142–153. https://doi.org/10.1053/j.saep.2004.03.004
Olson, M.E., Vizzutti, D., Morck, D.W., Cox, A.K., 1994. The parasympatholytic effects of atropine sulfate and glycopyrrolate in rats and rabbits. Can J Vet Res 58, 254–258.
Onuma, M., KONDO, H., ONO, S., MURAKAMI, A., HARADA, T., SANO, T., 2017. Retrospective investigation of cardiopulmonary resuscitation outcome in 146 exotic animals. J Vet Med Sci 79, 1611–1614. https://doi.org/10.1292/jvms.16-0360
Pachtinger, G., 2013. Monitoring of the Emergent Small Animal Patient. Veterinary Clinics: Small Animal Practice 43, 705–720. https://doi.org/10.1016/j.cvsm.2013.03.014
Paul-Murphy, J., 2007. Critical Care of the Rabbit. Veterinary Clinics of North America: Exotic Animal Practice, Emergency and Critical Care 10, 437–461. https://doi.org/10.1016/j.cvex.2007.03.002
Paul-Murphy, J., Ramer, J.C., 1998. Urgent care of the pet rabbit. Vet Clin North Am Exot Anim Pract 1, 127–152, vi-vii. https://doi.org/10.1016/s1094-9194(17)30158-5
Plunkett, S.J., McMichael, M., 2008. Cardiopulmonary resuscitation in small animal medicine: an update. J Vet Intern Med 22, 9–25. https://doi.org/10.1111/j.1939-1676.2007.0033.x
Rozanski, E.A., Rush, J.E., Buckley, G.J., Fletcher, D.J., Boller, M., RECOVER Advanced Life Support Domain Worksheet Authors, 2012. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 4: Advanced life support. J Vet Emerg Crit Care (San Antonio) 22 Suppl 1, S44-64. https://doi.org/10.1111/j.1476-4431.2012.00755.x
Schnellbacher, R., Olson, E.E., Mayer, J., 2012. Emergency Presentations Associated with Cardiovascular Disease in Exotic Herbivores. Journal of Exotic Pet Medicine, Emergency Presentation of Exotic Mammal Herbivores 21, 316–327. https://doi.org/10.1053/j.jepm.2012.09.007
3 Substance-Specific Evidence Review
Bassiakou, E., Xanthos, T., Papadimitriou, L., 2009. The potential beneficial effects of beta adrenergic blockade in the treatment of ventricular fibrillation. European Journal of Pharmacology 616, 1–6. https://doi.org/10.1016/j.ejphar.2009.06.019
DeWitt, E.S., Black, K.J., Thiagarajan, R.R., DiNardo, J.A., Colan, S.D., McGowan, F.X., Kheir, J.N., 2016. Effects of commonly used inotropes on myocardial function and oxygen consumption under constant ventricular loading conditions. J Appl Physiol (1985) 121, 7–14. https://doi.org/10.1152/japplphysiol.00058.2016
Downing, S.E., Chen, V., 1985. Myocardial injury following endogenous catecholamine release in rabbits. Journal of Molecular and Cellular Cardiology 17, 377–387. https://doi.org/10.1016/S0022-2828(85)80137-1
Harvey, M., Cave, G., Prince, G., Lahner, D., 2010. Epinephrine injection in lipid-based resuscitation from bupivacaine-induced cardiac arrest: transient circulatory return in rabbits. Anesth Analg 111, 791–796. https://doi.org/10.1213/ANE.0b013e3181e66050
Kii, N., Adachi, N., Yorozuya, T., Nagaro, T., Arai, T., 2004. Suppression of endogenous catecholamine release by anesthetics during cardiopulmonary resuscitation in the rabbit. Can J Anaesth 51, 404–405. https://doi.org/10.1007/BF03018255
Oyebola, P.D.D.O., 2011. Effect of adrenaline on glucose uptake in the rabbit small intestine. African Journal of Medicine and Medical Sciences 40, 225–233.
Towell, M.E., Lysak, I., Layne, E.C., Sayler, D., Bessman, S.P., 1981. The effect of epinephrine on blood and tissue PO2 in the rabbit. Circ Shock 8, 123–130.
4 Efficacy Evidence Review
Buckley, G.J., DeCubellis, J., Sharp, C.R., Rozanski, E.A., 2011. Cardiopulmonary Resuscitation in Hospitalized Rabbits: 15 cases. Journal of Exotic Pet Medicine, Zoonotic Diseases 20, 46–50. https://doi.org/10.1053/j.jepm.2010.11.010
Harvey, M., Cave, G., Prince, G., Lahner, D., 2010. Epinephrine injection in lipid-based resuscitation from bupivacaine-induced cardiac arrest: transient circulatory return in rabbits. Anesth Analg 111, 791–796. https://doi.org/10.1213/ANE.0b013e3181e66050
Kohlhauer, M., Darbera, L., Lidouren, F., Chenoune, M., Ghaleh, B., Vivien, B., Carli, P., Dabire, H., Berdeaux, A., Tissier, R., 2014. Comparative effect of hypothermia and adrenaline during cardiopulmonary resuscitation in rabbits. Shock 41, 154–158. https://doi.org/10.1097/SHK.0000000000000083
Onuma, M., KONDO, H., ONO, S., MURAKAMI, A., HARADA, T., SANO, T., 2017. Retrospective investigation of cardiopulmonary resuscitation outcome in 146 exotic animals. J Vet Med Sci 79, 1611–1614. https://doi.org/10.1292/jvms.16-0360
4.0 Efficacy Review
Buckley, G.J., DeCubellis, J., Sharp, C.R., Rozanski, E.A., 2011. Cardiopulmonary Resuscitation in Hospitalized Rabbits: 15 cases. Journal of Exotic Pet Medicine, Zoonotic Diseases 20, 46–50. https://doi.org/10.1053/j.jepm.2010.11.010
Harvey, M., Cave, G., Prince, G., Lahner, D., 2010. Epinephrine injection in lipid-based resuscitation from bupivacaine-induced cardiac arrest: transient circulatory return in rabbits. Anesth Analg 111, 791–796. https://doi.org/10.1213/ANE.0b013e3181e66050
Kii, N., Adachi, N., Yorozuya, T., Nagaro, T., Arai, T., 2004. Suppression of endogenous catecholamine release by anesthetics during cardiopulmonary resuscitation in the rabbit. Can J Anaesth 51, 404–405. https://doi.org/10.1007/BF03018255
Kohlhauer, M., Darbera, L., Lidouren, F., Chenoune, M., Ghaleh, B., Vivien, B., Carli, P., Dabire, H., Berdeaux, A., Tissier, R., 2014. Comparative effect of hypothermia and adrenaline during cardiopulmonary resuscitation in rabbits. Shock 41, 154–158. https://doi.org/10.1097/SHK.0000000000000083
Onuma, M., KONDO, H., ONO, S., MURAKAMI, A., HARADA, T., SANO, T., 2017. Retrospective investigation of cardiopulmonary resuscitation outcome in 146 exotic animals. J Vet Med Sci 79, 1611–1614. https://doi.org/10.1292/jvms.16-0360
5.0 Supplementary Evidence
5.1 UK SPC Links
Adrenaline 1 mg/10 ml (1:10,000), solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC) - (emc) [WWW Document], n.d. URL https://www.medicines.org.uk/emc/product/2024/smpc (accessed 1.23.24).
Adrenaline (Epinephrine) 1mg/ml (1:1000) solution for injection (ampoule) - Summary of Product Characteristics (SmPC) - (EMC) [WWW Document], n.d. URL https://www.medicines.org.uk/emc/product/3673/smpc (accessed 1.23.24).
Adrenaline (Epinephrine) Injection BP 1 in 1000 - Summary of Product Characteristics (SmPC) - (EMC) [WWW Document], n.d. URL https://www.medicines.org.uk/emc/product/6284/smpc (accessed 1.23.24).
Adrenaline Injection BP 1/1000 (1mg/1ml) - Summary of Product Characteristics (SmPC) - (EMC) [WWW Document], n.d. URL https://www.medicines.org.uk/emc/product/6595/smpc (accessed 1.23.24).
Dilute Adrenaline (Epinephrine) Injection 1:10,000 (ampoules) - Summary of Product Characteristics (SmPC) - (EMC) [WWW Document], n.d. URL https://www.medicines.org.uk/emc/product/3675/smpc (accessed 1.23.24).
5.2 Additional Material Consulted
Booth, D., 2011. Small Animal Clinical Pharmacology and Therapeutics - 2nd Edition [WWW Document]. URL https://shop.elsevier.com/books/small-animal-clinical-pharmacology-and-therapeutics/boothe/978-0-7216-0555-5 (accessed 1.24.24).
Maddison, G., 2008. Small Animal Clinical Pharmacology E-Book: 2nd edition | Edited by Jill E. Maddison | ISBN: 9780702037252 [WWW Document]. Elsevier Asia Bookstore. URL https://www.asia.elsevierhealth.com/small-animal-clinical-pharmacology-e-book-9780702037252.html (accessed 1.23.24).
Plumb, 2024. Epinephrine [WWW Document]. URL https://app.plumbs.com/drug/yTTIqZPq6HPROD?source=search&searchQuery=epineph§ion=doses (accessed 1.23.24).
PubChem, 2024. Epinephrine [WWW Document]. URL https://pubchem.ncbi.nlm.nih.gov/compound/5816 (accessed 2.24.24).
WHO, 2024. Adrenaline (Epinephrine) WHOCC - ATC/DDD Index [WWW Document]. URL https://www.whocc.no/atc_ddd_index/ (accessed 2.24.24).
5.3 Conference Proceedings
-
5.4 Expert Opinion
Additional material in collating the data displayed is expert opinion derived from clinical experience or reputable texts.
McArthur, S. (2024)
Monograph Details
Analysis Criteria
Species: Rabbit
Active Substance: Adrenaline (Epinephrine)
Indication: CPCR
Dosing Suggestion: 0.01 mg/kg, IV/IO every other cycle of basic life support (BLS)
Consensus Resources
Monograph Location: https://rabbit.evidence-base.org/dose/adrenaline-rabbit-dosing
Reference Location: https://www.zotero.org/groups/4741738/formulary_adrenaline
Monograph Document Folder: https://drive.google.com/drive/folders/1ApipxaTls-zHeQSCNJac7yP5ONl9LQuv?usp=drive_link
PICO and V-Grade Resources
Monograph Analysis Worksheet: https://docs.google.com/document/d/1X8LG8qb9ublS0eprubvTRYqYmT7wRTGon8927Iqx-98/edit?usp=sharing
Consensus Team
Monograph Authors: S McArthur; TBA (last updated 20/03/2024)
Monograph Editors: TBA (last updated 20/03/2024)
Monograph Contact
For permissions and further information about the Veterinary Consensus Initiative (VCI), please get in touch with us via Stuart McArthur B Vet Med MRCVS; Email: stuart.mcarthur@me.com
Terms and Conditions
Although our services are designed to provide accurate and authoritative information on the subject matter covered, VetConsensus collaborators (all members, employees, collaborators, consultants, sponsors and partners) make no representations and give no warranties, express or implied, about the accuracy or completeness of information, or associated recommendations.
-
We are not advising clinicians about specific patients under active treatment.
-
We are not endorsing any medicine, merchandise, protocol or technique by making available information and giving recommendations.
The information provided here is not a substitute for the exercise of professional judgment, for which an attending clinician is always responsible.
This database and its network of related websites are protected by copyright law. All rights are reserved.
-
Specific content, such as articles, photos, and images, is subject to the copyright of its respective owners. All rights reserved.
-
Unauthorised distribution, transmission or publication is strictly prohibited.
-
Materials obtained through our websites belong to their respective owners and are protected by national and international intellectual property laws, conventions, and treaties. Single copies may be used for personal, non-commercial purposes only.
All other rights are reserved, and commercial uses, including publication, retransmission, broadcast, posting to newsgroups, mail lists or electronic bulletin boards, circulation, selling, reproduction or redistribution in any medium, are prohibited, except with the prior written approval of the copyright owner. The Veterinary Publishing Company may take appropriate legal action if these rights are infringed.