Shock (SIRS)

Shock has different terminologies in modern critical care. Systemic Inflammatory Response Syndrome (SIRS) and other acronyms are used. For the purpose of this manual it refers to the manifestation of inadequate tissue oxygenation most often caused by decreased perfusion. It is characterized by the loss of homeostasis attributable to breakdown of hemodynamic control mechanisms that produces decreases in cardiac output and effective circulating volume, which results in an inadequate tissue perfusion.

Based on the etiology there are 6 different types of shock 

• Hypovolemic
  • Hemorrhage
  • Fluid deficits
• Distributive
  • Sepsis
  • Anaphylaxis − Neurogenic
• Cardiogenic
  • Heart failure
• Obstructive
  • Pulmonary emboli
  • Cardiac tamponade
• Hypoxic
  • Severe hypoxemia
  • Inability to utilize oxygen
• Metabolic
  • Severe hypoglycemia
  • Adrenal dysfunction

Signs of impending arrest:

• Bradycardia or asystole
  • <40-60 bpm or irregular HR
• Irregular to absent RR
  •  < 10 bpm, gasping
• Mydriasis
  • Sluggish or nonresponsive papillary response
• Marked hypotension 
  • No pulse pressure
• Monitoring
  • Sudden decrease in end tidal (ET) CO2 indicates cardiac output is low

Two main causes of arrest in foals

• Peripartum asphyxia - HYPOXEMIA
  • Focus: oxygenate and ventilate
  • Prognosis good if intervention is early
• Secondary to metabolic derangements /septic causes
  • Focus: traditional ABC approach
  • Prognosis poor (severely ill foal)

These are managed slightly differently, and carry a different prognosis

Which foals are candidates for CPR?

• Those with potentially reversible disease processes
• Peripartum asphyxia
• Otherwise healthy foal – dystocia, C-section etc.

Foals with metabolic diseases that are potentially treatable

• HYPP
• Uroperitoneum
• Hypovolemic shock

Basic Haemodynamic Monitoring

• Physical Exam (See Chapter 11 - Physical Exam of the Equine Neonate)
  • Mentation
  • Heart rate
  • Pulse pressure and temperature of the extremities
  • Mucous membranes
  • Other signs: respiratory rate, skin turgor, sunken eyes.
• CBC/Chemistry/IgG/Fibrinogen/Lactate/Clotting Profile
  • (See normal values at Chapter 72 - Hematology and Clinical Chemistry norm values - United States
    and Chapter 73 - Hematology and Clinical Chemistry norm values - European)
• Arterial Blood Gases
  • Capnography, Pulse oximetry (See Chapter 74 - Blood Gases).
• Urine Output¹
  • Urinal Output is an important indicator of renal blood flow and glomerular filtration rate. Hemodynamic interventions that are increasing urinary output are likely to be beneficial. Minimum output should be 2-4 ml/kg/h. Normal urinary output is 6 ml/kg/h.
• Arterial Blood Pressure (ABP) and Central Venous Pressure (CVP).^2-5
  • Arterial blood pressure (ABP) can be fairly accurately measured with indirect measurements using a #4 neonatal cuff. Doppler measurements can also be performed.

    Direct measurements using an intra-arterial catheter connected to a pressure transducer are the most accurate; however they require advanced maintenance. Reported mean arterial values (MAP) for healthy foals are 84±3.7mmHg at birth and 101.3±4.4 mmHg at 2 weeks of age, when using the direct measurement and 95±13 when using the indirect technique. Mean ABP should always be maintained above 60 mmHg and is both an important target and an indicator of the therapy. Decreased ABP can occur during decreased cardiac output as well as decreased vascular resistance (vasodilatation).

  • Central Venous Pressure (CVP) is the intraluminal pressure within the cranial vena cava. It is regulated by
    • Central venous blood volume
    • Venomotor tone
    • Cardiac function

The optimal central venous pressure in foals is approximately 2-10 chg.20. Normal CVP is the end point of the fluid resuscitation. Measurements require 20 cm catheter (double or triple lumen). CVP is measured as the mean of the a-wave (pressure change during atrial contraction). Persistent elevation of CVP increases the risk for edema formation and should be avoided.

•  Cardiac Output, Stroke Volume, Systemic Vascular Resistance
  • These measurements are advanced and time-consuming although they can be performed in animals with no financial constraints or special conditions.

Treatment of Shock

Fluid replacement (resuscitation⁶) 

If the CVP is low, administer an IV bolus of fluids (See Chapter 22 - Fluid and Electrolyte Balance).

• Replacement fluid therapy: LRS, Plasma-lyte 148, Normosol R: 10-20 ml/kg then reassess.
• Colloid therapy
  •  Plasma: 10-25 ml/kg

Inotropic and Vasopressor therapy^6-8

Fluid therapy acts to increase stroke volume by increasing end diastolic volume of the ventricle, whereas inotropic drugs decrease end-systolic volume by increasing myocardial contractions and therefore increasing stroke volume. Neonates require inotropic drugs if they are unresponsive to proper fluid therapy or exhibit normal or elevated CVPs while having impaired peripheral oxygenation.

• Dobutamine is a synthetic sympathomimetic drug (adrenergic agonist) that has a high affinity to β1- adrenoceptors and weak affinity to α-adrenergic receptors. It increases cardiac stroke volume and improves splanchnic perfusion presumably through its action on β2 receptors. It should be diluted in D5W or LRS and given as a continuous rate of infusion a dose starting at 1-5ug/kg/min. Vasopressor agents act through the stimulation of vascular smooth muscle tone, therefore have an important role of redistributing the circulating blood volume and increasing the peripheral vascular resistance (PVR).
• Norepinephrine is a strong α-adrenergic stimulant and has some affinity to β1-adrenoceptors. It is useful to restore organ perfusion in vasodilatory shock. It also improves cardiac output as a result of its effect on β1-adrenoceptors. It may be used in combination with dobutamine at a starting dose of 0.1ug/kg/min to a maximum dose of 1.5 ug/kg/min^9,10
• Epinephrine is a potent non-selective α- and β- adrenergic stimulant. Although it is a potent vasopressor it has been shown to have detrimental effect on splanchnic circulation, therefore is not recommended as a first line vasopressor. Starting dose of epinephrine is 0.1 ug/kg/min.
• Phenylephrine has been shown to decrease stroke volume in healthy anesthetized horses. Therefore, its use is not recommended in equine patients.
• Dopamine in recent human studies failed to demonstrate beneficial effect of dopamine on splanchnic circulation; it may actually have detrimental effect on organ perfusion. In addition, dopamine suppresses the production of anterior pituitary hormones except for ACTH in humans.

• Vasopressin also known as antidiuretic hormone (ADH)
  • Healthy anesthetized foals had increased mean arterial pressure (MAP) after administration of vasopressin.
  • Vasopressin has been shown to be potent in cases of sepsis or endotoxemia. It restores vasoconstrictor effects of catecholamines and is also a highly powerful vasoconstrictor alone. This effect may reduce cardiac output, and therefore it is recommended to administer in conjunction with an inotropic drug. The major side effect of the drug is the dose dependent decrease on splanchnic perfusion. Suggested dose in foals is 0.25-1.5 mU/kg/min.
• Methylene Blue limited information. The proposed effect is the inhibition of NOS, a nitric oxide producing enzyme, and therefore decreasing the vasodilation and increasing the myocardial contractility. Side effects include methemoglobinemia, staining of the skin and the urine. Further investigations are needed before the introduction of this drug in the equine neonatal medicine.

In Summary inotropic and vasopressor therapy must always be addressed to the individual animal. Response to treatment should always be closely monitored. One should restore circulating blood volume first by administering iv crystalloids and/or colloids, because combination of hypovolemia and vasopressor therapy has detrimental effects on stroke volume and on organ perfusion. Current evidence suggests that the first choice inotrope is dobutamine in the equine neonate. If the animal remains hypotensive, vasopressor therapy is also indicated (norepinephrine, vasopressin).¹¹

Corticosteroids

The use of corticosteroids in shock remains controversial¹². Administration of low dose corticosteroids shorten the periods of shock but it does not improve survival rates¹¹. If given, physiological doses of short acting steroids should be used only (50 mg prednisolone sodium succinate IV). Larger doses should always be avoided.

NSAIDs

Low dose flunixin meglumine (Banamine®) 0.25 mg/kg QID has been shown to lessen manifestations of endotoxemia when administered early but it may contribute to gastric ulceration, decrease renal perfusion and cause medullary crest necrosis .

Pentoxifylline 

Pentoxifylline is a rheological agent, which has a phosphodiesterase antagonist effect as well as TNF-α blocking properties. It is used in horses for the treatment of endotoxemia, sepsis and for prevention of laminitis. It can be administered in a dose of 7.5 mg/kg iv diluted in fluids or orally every 8-12 hours.

Polymyxin-B

Polymyxin-B is an antibiotic that has endotoxin-binding properties. It is likely beneficial in endotoxic and septicemic patients. Administration is associated with nephro and neurotoxicity. Dose is 1000-6000 U/kg/12 h iv.

Antioxidants and Vitamins

Antioxidants and Vitamins may be added to combat against increased free radical production. DMSO can be given at a dose of 0.1-1 g/kg IV BID. Others have used allopurinol 40mg/kg PO, vitamin C at a dose of 50mg/kg IV SID and Vitamin E 10-40 U/kg PO SID. EC- Don’t give any of these during period of “open gut” (<12 hrs of age).

Hyperimmune plasma 

Hyperimmune plasma (J5) (See Chapter 10 - Plasma Therapy) may have the additional benefit of containing anti- endotoxin antibodies as well as serving as an oncotic support and providing clotting factors.
Antibiotics (see Chapter 70 - Guidelines for Drug Use in Equine Neonates) are an essential part of the therapy during bacterial septic shock. A recent study has demonstrated that the administration of B- lactam antibiotics further increases the
concentration of endotoxin in circulation due to destruction of the bacterial wall components. Therefore, anti-endotoxic therapy may be considered in conjunction with antimicrobial therapy.

Anti-coagulants

Anti-coagulants have been used widely in equine medicine to decrease the incidence of coagulopathies during procoagulant stages. Unfractionated heparin acts as a potent cofactor of ATIII, although it can cause aggregation of red blood cells and a reversible decrease in PCV. The dose is 20-100 U/kg TID. Low molecular weight heparin (dalteparin, enoxaparin) binds to factor X and V, and has less effect on ATIII. The dose of dalteparin is 50 U/kg SID. The dose of enoxaparin is 40 U/kg SID. Parenteral nutrition. Foals with shock or sepsis usually are not able to tolerate enteral nutrition. See Chapter 23 for details.

Insulin therapy

Insulin therapy maybe indicated in foals with shock or sepsis. A recent study has shown decreased survival rates in foals with persistent hyperglycemia or hypoglycemia¹³.