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Adrenaline

Grade

Resuscitation


Adrenaline (Epinephrine) administration is recommended where spontaneous circulation return (ROSC)  has not occurred within the initial two BLS cycles and after administering any anaesthetic reversal agent.

Initial Dosing

  • CPCR: 0.01 mg/kg, IV/IO  every other cycle of basic life support (BLS) (Fletcher et al., 2012).

Subsequent Dosing

  • Ongoing CPCR: Deliver 0.01 mg/kg as an IV or IO bolus every other cycle of BLS, i.e. every 3–5 minutes.

  • Number of Administrations: The maximum canine adrenaline dose over time, so the optimum number of administrations during CPCR is unknown for the dog. VCI recommends a maximum of four administrations, or two if use is alternated with Vasopressin.

Basic Life Support (BLS)

Once CPA is suspected or confirmed, basic life support (BLS) should be initiated.


  1. Chest Compressions: Chest compressions should be initiated immediately on recognition of CPA. Thoracic compressions in left or right lateral recumbency are recommended for most dogs. In deep, narrow-chested dogs like greyhounds, chest compressions with the hands directly over the heart are recommended, with the patient in either lateral recumbency. For barrelchested dogs (e.g. English Bulldogs), sternal compressions directly over the heart with the patient in dorsal recumbency are recommended (Fletcher et al., 2012; Hopper et al., 2012).

  2. Ventilation Support: Ventilatory support should be offered after initiation of chest compressions and is aimed at reducing both hypoxia and hypercapnia. Intubation of animals in lateral recumbency is ideal to avoid interrupting chest compressions.

  3. Compression-to-ventilation Ratio (C:V Ratio): The RECOVER program suggests that a ten breaths/min ventilation rate with a tidal volume of 10 mL/kg and a short inspiratory time of 1-second suits intubated canine patients. For non-intubated patients, 30 chest compressions at a rate of 100–120/min, followed by two breaths delivered quickly (Mouth to snout or ambu bag), is recommended (Fletcher et al., 2012; Hopper et al., 2012).

  4. Cycle Timing: We propose 2 minutes of uninterrupted chest compressions before checking the rhythm, which may suit canine CPR patients. In humans, this timing is associated with increased survival compared to more frequent pauses in CPR (Hopper et al., 2012).

Advanced Life Support (ALS)

After initiating BLS to support systemic circulation, a functional airway, and ventilation, those members of the veterinary team not actively involved in chest compressions or ventilation support should help provide advanced life support (ALS). This generally includes:

1 Vascular and Intraosseous Access

Patients who require CPCR as a consequence of general anaesthesia are likely to have vascular access already. Animals without vascular access should be canulated.

2 Medications

Vasopressors such as Adrenaline (Epinephrine) or Vasopressin are an essential component of ALS drug therapy.


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: Reverses the sedative effects of alpha2-adrenoreceptor Agonist Agents, typically Medetomidine and Dexmedetomidine components of multimodal anaesthesia protocols.

  • Flumazenil: Reverses benzodiazepine components of multimodal anaesthesia protocols.

  • Naloxone: Reverse full and partial opiate agonists


Adrenaline (Epinephrine): A nonspecific adrenergic agonist catecholamine 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. Its use should, therefore, be limited to what is necessary to achieve ROSC (Bassiakou et al., 2009; Fletcher et al., 2012; Maddison, 2008; Plumbs, 2023).


  • Adrenaline (Epinephrine): Dosing is covered here in this monograph.


Vasopressin: An option in countries where it is available. Vasopressor effects are mediated through V1 receptors located on peripheral vascular smooth muscle, a mechanism independent of the ⍺1 effects of Epinephrine (Fletcher et al., 2012).


  • Vasopressin: 0.8 U/kg, IV,  alternating with Epinephrine every other BLS cycle (Fletcher et al., 2012).


Anticholinergic Agents: Evidence supporting the use of anticholinergic agents, e.g. Atropine or Glycopyrrolate during CPR, is limited. Anticholinergic agents are considered an additional drug rather than a sole intervention. Dogs 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 dogs or cats (Rozanski et al., 2012).



3 Monitoring

Monitoring is part of advanced life support and post-CRCR care. Monitoring equipment will vary with the clinical setting. As BLS cycles are set at two minutes, the onset of CPCR should be recorded, and cycle time should be monitored per RECOVER guidelines.

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 suggests that chest compressions achieve peripheral perfusion.

  • Pulse Oximetry: After initiating cardiac compressions, pulse detection using oximetry indicates that chest compressions achieve peripheral perfusion.

  • 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 impending reoccurrence of CPA (Fletcher et al., 2012).

4 Additional Nursing Support

  1. Thermal Support: Hypothermia leads to altered coagulation, organ dysfunction, and electrolyte and acid-base abnormalities. The support team should thermally manage patients during BLS and ALS. 

  2. Fluid Support: Cardiogenic, distributive, or septic shock patients require appropriate circulatory support. Guidelines can be located in RECOVER guidelines (Fletcher et al., 2012).

Alternative Protocols

  • Vasopressin: Alternating Vasopressin with Epinephrine following every other BLS cycle above is an option if Vasopressin is available.

  • Salvage Dosing: Where 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  if no other beneficial therapeutic options are apparent (Fletcher et al., 2012).


Therapeutics

Therapeutics

RECOVER-Based Recommendations

Our recommendations for canine CPCR follow RECOVER guidelines for cardiopulmonary cerebral resuscitation (CPCR) to reverse cardiopulmonary arrest (CPA).


Administration of Adrenaline (Epinephrine) is one component of advanced life support (ALS) offered following the provision of basic life support (BLS) and alongside it during canine CPCR. 


Administration of Adrenaline is not a substitute for providing basic life support components, which include the recognition of CPA, chest compressions, securing an airway, and providing ventilation (Hopper et al., 2012; Hall, 2023). For this monograph, one BLS cycle is 2 minutes of uninterrupted compression/ventilation (Fletcher et al., 2012).


CPCR is an emergency procedure; any members of the veterinary CPCR team not active in BLS should help make provisions for appropriate ALS (described below).

Sole Use

The optimal Adrenaline protocol during ALS is yet to be determined. Sole use 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 CPCR, various agents can be administered alongside Adrenaline. VCI recommends that clinicians consider multimodal use if the criteria within this monograph appear to have been met. During  CPCR, various agents can be administered alongside Adrenaline:


  • Anaesthetic Reversal Agents: These are covered in detail in our dosing recommendations

  • Vasopressor agents: Administration of vasopressin alternating with Adrenaline (Epinephrine) every other cycle is an option where it is available.

  • Anticholinergic Agents: Animals with high vagal tone and subsequent bradycardia/asystole (e.g., gastrointestinal pain or prolonged dyspnoea)  may benefit from using atropine or glycopyrrolate (Rozanski et al., 2012).

Efficacy

The efficacy profile for Adrenaline use during CPCR  


  • Anaesthetic-induced PEA CPA: We recommended that CPCR is always appropriate in ASA 1 and 2 animals requiring CPCR due to general anaesthesia and is likely to be effective if undertaken promptly in line with the advice here.

  • 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 any resuscitation endpoint, as there are situations where resuscitation is both unwise and unable to return adequate quality of life to be justifiable.  The efficacy of our adrenaline protocol in spontaneous CPA is unknown.

Treatment Goals

  • ROSC: Adrenaline administration aims to recover spontaneous circulation with minimum damage to the patient, i.e., to combine use with optimum BSL, minimum trauma, and to limit excessive administration of adrenaline.

Treatment Endpoints

  • ROSC: Because excessive Adrenaline appears to reduce CPCR recovery rates, additional adrenaline should be avoided if ROSC has been achieved.

Abbreviations Used

  • ALS | Advanced Life Support

  • BLS |  Basic Life Support

  • CPA | Cardiopulmonary Arrest

  • CPR | Cardiopulmonary Resuscitation

  • CRT | Capillary Refill Time

  • PEA | Pulseless Electrical Activity

  • RVF | Refractory Ventricular Fibrillation

  • ROSC | Return of Spontaneous Circulation

  • RECOVER | Reassessment Campaign on Veterinary Resuscitation

  • VF | Ventricular Fibrillation

  • VT | Ventricular Tachycardia


Evidence

Evidence Base

1 Species-Specific Evidence Review 

  1. Gatson, B.J., Swift, S., Paranjape, V., 2022. Successful treatment of prolonged refractory ventricular fibrillation in an anesthetized dog. J Vet Emerg Crit Care (San Antonio) 32, 129–134. https://doi.org/10.1111/vec.13132

2 Condition-Specific Evidence Review

  1. 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

  2. Boller, M., Fletcher, D.J., 2012. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 1: Evidence analysis and consensus process: collaborative path toward small animal CPR guidelines. Journal of Veterinary Emergency and Critical Care 22, S4–S12. https://doi.org/10.1111/j.1476-4431.2012.00758.x

  3. Brainard, B.M., Boller, M., Fletcher, D.J., RECOVER Monitoring Domain Worksheet Authors, 2012. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 5: Monitoring. J Vet Emerg Crit Care (San Antonio) 22 Suppl 1, S65-84. https://doi.org/10.1111/j.1476-4431.2012.00751.x

  4. de Oliveira, F.C., Feitosa-Filho, G.S., Ritt, L.E.F., 2012. Use of beta-blockers for the treatment of cardiac arrest due to ventricular fibrillation/pulseless ventricular tachycardia: A systematic review. Resuscitation 83, 674–683. https://doi.org/10.1016/j.resuscitation.2012.01.025

  5. Fletcher, D.J., Boller, M., 2021. Fluid Therapy During Cardiopulmonary Resuscitation. Front Vet Sci 7, 625361. https://doi.org/10.3389/fvets.2020.625361

  6. Fletcher, D.J., Boller, M., 2013. Updates in Small Animal Cardiopulmonary Resuscitation. Veterinary Clinics of North America: Small Animal Practice, Emergency Medicine 43, 971–987. https://doi.org/10.1016/j.cvsm.2013.03.006

  7. 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

  8. Gatson, B.J., Swift, S., Paranjape, V., 2022. Successful treatment of prolonged refractory ventricular fibrillation in an anesthetized dog. J Vet Emerg Crit Care (San Antonio) 32, 129–134. https://doi.org/10.1111/vec.13132

  9. Henik, R.A., 1992. Basic life support and external cardiac compression in dogs and cats. J Am Vet Med Assoc 200, 1925–1931.

  10. Hoehne, S.N., Kruppert, A., Boller, M., 2020. [Small animal cardiopulmonary -resuscitation (CPR) in general practice]. Schweiz Arch Tierheilkd 162, 735–753. https://doi.org/10.17236/sat00280

  11. Hofmeister, E.H., Brainard, B.M., Egger, C.M., Kang, S., 2009. Prognostic indicators for dogs and cats with cardiopulmonary arrest treated by cardiopulmonary cerebral resuscitation at a university teaching hospital. J Am Vet Med Assoc 235, 50–57. https://doi.org/10.2460/javma.235.1.50

  12. 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

  13. Kass, P.H., Haskins, S.C., 1992. Survival Following Cardiopulmonary Resuscitation in Dogs and Cats. Journal of Veterinary Emergency and Critical Care 2, 57–65. https://doi.org/10.1111/j.1476-4431.1992.tb00093.x

  14. McMichael, M., Herring, J., Fletcher, D.J., Boller, M., the RECOVER Preparedness and Prevention Domain Worksheet Authors, 2012. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 2: Preparedness and prevention. Journal of Veterinary Emergency and Critical Care 22, S13–S25. https://doi.org/10.1111/j.1476-4431.2012.00752.x

  15. Oppenheimer, N., Kelmer, E., Shwartzshtei, N., Segev, G., Ohad, D., Klainbart, S., 2022. Retrospective evaluation of the outcome and prognosis of undergoing positive pressure ventilation due to cardiac and noncardiac causes in dogs and cats (2019–2020): 101 cases. Journal of Veterinary Emergency and Critical Care 32, 769–776. https://doi.org/10.1111/vec.13224

  16. 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

  17. Smarick, S.D., Haskins, S.C., Boller, M., Fletcher, D.J., Authors,  the R.P.-C.A.C.D.W., 2012. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 6: Post-cardiac arrest care. Journal of Veterinary Emergency and Critical Care 22, S85–S101. https://doi.org/10.1111/j.1476-4431.2012.00754.x

  18. Wingfield, W.E., Van Pelt, D.R., 1992. Respiratory and cardiopulmonary arrest in dogs and cats: 265 cases (1986-1991). J Am Vet Med Assoc 200, 1993–1996.

3 Substance-Specific Evidence Review

  1. Tuttle, R., Popescu, L., Hill, S., Slanczka, A., Jankowski, J., Barre, K., Krueger, E., Slade, D., Croutch, C., Robben, M., Mesa, Z., Mesa, M., Dretchen, K.L., 2020. Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model. Respir Res 21, 78. https://doi.org/10.1186/s12931-020-01343-x

4 Efficacy Evidence Review

  1. Gatson, B.J., Swift, S., Paranjape, V., 2022. Successful treatment of prolonged refractory ventricular fibrillation in an anesthetized dog. J Vet Emerg Crit Care (San Antonio) 32, 129–134. https://doi.org/10.1111/vec.13132

  2. Hoehne, S.N., Hopper, K., Epstein, S.E., 2019. Prospective Evaluation of Cardiopulmonary Resuscitation Performed in Dogs and Cats According to the RECOVER Guidelines. Part 2: Patient Outcomes and CPR Practice Since Guideline Implementation. Front Vet Sci 6, 439. https://doi.org/10.3389/fvets.2019.00439

  3. Hofmeister, E.H., Brainard, B.M., Egger, C.M., Kang, S., 2009. Prognostic indicators for dogs and cats with cardiopulmonary arrest treated by cardiopulmonary cerebral resuscitation at a university teaching hospital. J Am Vet Med Assoc 235, 50–57. https://doi.org/10.2460/javma.235.1.50

  4. Kass, P.H., Haskins, S.C., 1992. Survival Following Cardiopulmonary Resuscitation in Dogs and Cats. Journal of Veterinary Emergency and Critical Care 2, 57–65. https://doi.org/10.1111/j.1476-4431.1992.tb00093.x

  5. Oppenheimer, N., Kelmer, E., Shwartzshtei, N., Segev, G., Ohad, D., Klainbart, S., 2022. Retrospective evaluation of the outcome and prognosis of undergoing positive pressure ventilation due to cardiac and noncardiac causes in dogs and cats (2019–2020): 101 cases. Journal of Veterinary Emergency and Critical Care 32, 769–776. https://doi.org/10.1111/vec.13224

  6. Perondi, M.M., Reis, A.G., Paiva, E.F., Paolo, S., 2002. HIGH-DOSE EPINEPHRINE IS WORSE THAN STANDARD-DOSE EPINEPHRINE AS RESCUE THERAPY FOR PEDIATRIC CARDIAC ARREST: A PROSPECTIVE, RANDOMIZED CONTROLLED TRIAL: 11. Critical Care Medicine 30, A3.

  7. Wingfield, W.E., Van Pelt, D.R., 1992. Respiratory and cardiopulmonary arrest in dogs and cats: 265 cases (1986-1991). J Am Vet Med Assoc 200, 1993–1996.

5 Supplementary Information 

5.1 UK SPC Links

  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. 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

  1. Adrenaline (Epinephrine) WHOCC - ATC/DDD Index [WWW Document], 2024. URL https://www.whocc.no/atc_ddd_index/ (accessed 2.24.24).

  2. 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).

  3. 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).

  4. Plumb, 2024. Epinephrine [WWW Document]. URL https://app.plumbs.com/drug/yTTIqZPq6HPROD?source=search&searchQuery=epineph&section=doses (accessed 1.23.24).

  5. PubChem, 2024. Epinephrine [WWW Document]. URL https://pubchem.ncbi.nlm.nih.gov/compound/5816 (accessed 2.24.24).

  6. Quesenberry, K.E. (Ed.), 2021. Ferrets, rabbits, and rodents: clinical medicine and surgery, Fourth edition. ed. Elsevier, St. Louis, Missouri.

  7. 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).


Monograph Details

Monograph Details

Analysis Criteria

  • Species: Canine

  • Active Substance: Adrenaline (Epinephrine)

  • Indication: CPCR

  • Dosing Suggestion: 

Consensus Resources

PICO and V-Grade Resources

  • Monograph Analysis Worksheet: 

Consensus Team

  • Monograph Authors: S McArthur; TBA (last updated 20/03/2024)

  • Monograph Editors: TBA (last updated 20/03/2024)

Monograph Contact


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