CPR: BASIC LIFE SUPPORT Amy Newfield, CVT, VTS (ECC) BluePearl-Waltham, MA, USA

Transcription

1 CPR: BASIC LIFE SUPPORT Amy Newfield, CVT, VTS (ECC) BluePearl-Waltham, MA, USA Please note: The first set of veterinary specific CPR guidelines were published in June of 2012 by the RECOVER campaign in the Journal of Veterinary Emergency and Critical Care. (Special Issue: Reassessment Campaign on Veterinary Resuscitation: Evidence and Knowledge Gap Analysis on Veterinary CPR, June 2012, Volume 22, Issue s1, Pages i i, S1 S131) For more specific information on CPR in animals please go to where a link can be found to the guidelines. INTRODUCTION Cardiopulmonary arrest (CPA) occurs because of the cessation of spontaneous and effective ventilation and a failure of the ventricles of the heart to contract causing no systemic perfusion. There are a myriad of diseases or injuries that can cause CPA to occur. For years, in veterinary medicine, the term cardiopulmonary cerebrovascular resuscitation (CPCR) or cardiopulmonary cerebral resuscitation has been used. Recently the Reassessment Campaign on Veterinary Resuscitation (RECOVER) has recommended going back to the term cardiopulmonary resuscitation (CPR) stating that it is less confusing and more universal. No matter what it is termed, it is inevitable in emergency medicine that at some point you will be faced with an arrest. While cardiopulmonary cerebral resuscitation in veterinary medicine is fairly unsuccessful (reports less than 6% in dogs and cats, 22% in humans) the speed at which you initiate resuscitative measures is imperative to the overall chance of survival for the patient. These notes will focus on basic life support based on the RECOVER campaign. PHASES There are three phases to CPR: Basic, Advanced and Prolonged. Basic life support is limited to the ABCs (airway, breathing, circulation) of CPR. Recently recommendations have been changed to CABs because it has been shown that starting with cardiac compressions first offers a better chance of survival. The goal is to support ventilation, oxygenation and circulation by administering manual and external chest compressions and ventilation. In human medicine basic life support also include defibrillation with an automated external defibrillator (AED). Once basic life support has been initiated a decision should be made very quickly if advanced life support techniques are needed. Most of the time they are needed and quick intervention with defibrillation and drugs offers patients the best chance of survival. Basic life support should be continued while advanced life support options are being prepared. Once the heart is beating on its own, prolonged life support should be started. The patient must be closely monitored for any changes in cardiovascular, respiratory or central nervous system. Reoccurrence of arrest is the biggest concern following resuscitation. BASIC LIFE SUPPORT In order to understand how to appropriately perform basic life support it is important to understand some common terminology when dealing with CPA patients. Asystole: Complete cessation of electrical & mechanical heart activity Pulseless Electrical Activity: Occurs when the electrical system continues, but mechanical activity ceases Ventricular Fibrillation and Pulseless V-Tach: Uncoordinated mechanical activity of the muscle cells (leads to a quivering activity or very rapid ineffective ventricular contraction) Cardiac Output: Product of stroke volume (how much the heart is pumping out) and heart rate (how fast it is pumping). Failure of either of these mechanisms can cause poor cardiac output. There are three types of arrest: cardiac, respiratory or cardiopulmonary arrest. A cardiac arrest only is where just the heart stops. This can be because of anaphylaxis, drug induced or disease. It is not common and offers a poor prognosis. Respiratory only arrest can occur because of smoke or water inhalation or can be 242

2 induced from drugs (propofol, anaesthesia). Respiratory only arrest offers a better chance of survival in younger animals where no underlying disease process is occurring. Most full arrests will start with a respiratory arrest and then continue into a full cardiopulmonary arrest. If just a respiratory arrest has occurred and the pet is under the influence of a reversible drug, the drug should be immediately reversed. Benzodiazepines (Diazepam): Reverse with flumazenil Opioids (Morphine, Oxymorphone, Buprenex): Reverse with naloxone Alpha-2 Agonist (Xylazine, Dexmedetomidine): Reverse with Yohimbine, Atipamezole If a suspected arrest occurs it is important to quickly assess if the pet has any cardiac or respiratory function. If you are unsure if the patient and do not have the ability to assess the patient quickly, you should perform chest compressions immediately. There is less then 2% significant complications related to performing chest compression on a human or animal that still has a beating heart. Of those complications (heart arrhythmias) most resolve or can be treated with medication. The most common complications seen when doing CPR are rib fractures and muscle damage. In order to assess if a patient has cardiac or respiratory function you can perform: Visual Inspection: Do not confuse agonal/gasping with normal breathing Palpation of pulses: Femoral, dorsal pedal, feel chest for heart beat Auscultation of heart: Most time consuming way to detect life Chest Compressions If a patient is in full cardiopulmonary arrest or cardiac arrest you will start with chest compressions. If the patient is in respiratory arrest only the cardiac function should be closely monitored while ventilatory support is administered. Even if performed correctly, most people will only produce 30% of normal stroke volume when performing chest compressions. Poorly performed compressions will generate even smaller stroke volumes. Good technique should include: Not leaning in on the patient because it decreases the recoil of the chest Working to compress the chest 1/3-1/2 the width of the chest Elevate your body above that of the pet so that you have good leverage Lock your elbows and hands and compress using your shoulders, not your arms Shoulders should be positioned above your hands in a direct line Currently the recommendation is to give compressions per minute. There are some references that indicate that perhaps giving as many as 150 compressions per minute may be better, but the evidence is not substantial enough. Giving more compressions than the recommended amount does not allow for the chest to recoil in full thus decreasing the stroke volume being produced. Depending on the size of the patient, most people cannot effectively compress the chest for more than 2 minutes at a time. It is recommended to switch persons every 2 minutes. Once someone is feeling tired, the technique of the compressions decreases dramatically causing poor cardiac output. It takes 1 minute of compressions for aortic blood pressure to reach a steady state. When switching people it is important that the switch occurs quickly and smoothly. Ideally the chest should continued to be compressed without any stoppage in between. There are two compression technique: Cardiac Pump and Thoracic Pump theory. In the cardiac pump theory arterial blood flow is a result of direct compressions of the ventricles. Compression is applied directly to the heart itself. This technique is best utilized in smaller patients (cats, small dogs) and those with triangle/pointed shaped chests (whippets, greyhounds). It is important to note that in some obese or older pets, the cardiac pump theory may not be effective because the chest may be too stiff for cardiac pumps. In these pets it may be better to use the thoracic pump theory. Ultimately the decision of what technique to use must be made quickly. There is not a lot of evidence based literature stating that failure to pick one technique over the other results in a better outcome. That being said compressions performed using the cardiac pump technique in smaller pets and those with triangle/pointed chests will result in better cardiac output during compressions. To locate the heart to perform the cardiac pump technique pull up on the pet's front leg so that the elbow touches the chest. Where the elbow meets the chest is where the chest compression should occur. The thoracic pump theory is based on the concept that the external chest compressions raise overall intrathoracic pressure and push blood from the aorta into the systemic circulation. 243

3 Compressions are performed over widest part of the chest. This technique will offer better cardiac output in deep chested or large breed dogs (Great Danes, Labradors, Retrievers)where it may be difficult to compress the heart directly (cardiac theory). During CPR it is important to attach an ECG to the pet. While it is not required it makes quickly assessing if the patient has a rhythm faster than auscultation. Arrhythmias can also be seen faster and appreciated easier so that drugs and defibrillation can occur during appropriate times. Failure to place an ECG leaves those performing CPR wondering how the pet is responding. If compressions are being performed correctly, the ECG may produced electronic activity as if the heart is beating. This is a good indication if adequate compressions are being administered. When to Stop Compressions It is currently recommended that rescuers performing chest compressions switch off every 2 minutes to avoid rescuer fatigue. It may not be possible to perform chest compressions for a full 2 minutes if it is a large pet. Compressions are physically exhausting. Switching off should occur as quick as possible to minimize interruptions. It is possible to switch off where no interruptions occur by having someone perform chest compressions next to the person and then take over compressing at the very next compression. Rarely ventricular fibrillation may occur. This arrhythmia is shockable. Therefore it seems okay to stop at the 2 minute point to check the ECG for a fibrillating rhythm. That being said current research shows that continuous compressions without interruptions allows for greater return of neurological outcome and survival. If you must stop compressions, stop quickly at 2 minutes and then immediately resume. There should never be any other reason to stop compressions other than rescuer switch-off, ECG check or the end of the attempt of CPR. How to Position the Pet There has been much discussion about whether pets should be in right/left lateral recumbency or dorsal/ventral recumbency for compressions. While there is not a lot of evidence based literature supporting better outcomes it is recommended that flat chested animals (Bulldogs, Frenchies, etc) should have chest compressions performed in dorsal recumbency. This allows for better recoil of the chest. Because it can be difficult to stabilize in dorsal recumbency one should consider placing the pet in a trough. This may be time consuming or not possible and if good technique chest compressions are not being performed because of movement of the animal, then lateral recumbency should occur. For pets or cats that have flatter and triangle/pointed chests, chest compressions should occur in lateral recumbency. There is no evidence based literature that supports right versus left recumbency offers a better outcome. Interposed Abdominal Compressions There has been some evidence that alternating compressions of the cranial abdomen and chest at a rate of compressions/minute in larger animals may help to improve the success rate of CPR. Ultimately these help to facilitate venous return from the abdomen and improve cardiac output. Because most veterinary staff do not have adequate experience in basic CPR, let alone interposed abdominal compressions it is not advised to attempt this technique because it will redirect the focus away from providing good technique chest compressions to the pet. However, if staff have practiced and are trained in this technique there is evidence it may help to provide better cardiac output. The RECOVER campaign recommends: "There is minimal evidence of abdominal trauma due to the use of interposed abdominal compressions when rescuers are trained in the technique....the use of interposed abdominal compressions in dogs and cats with CPA is reasonable when sufficient personnel trained in its use are available." Airway Without question chest compressions are the single more important aspect of CPR. There is much evidence based literature in human medicine and from the American Heart Association showing improved CPR statistics when chest compression only CPR is performed and/or when chest compressions are started before airway and breathing. There are three ways to gain access to the airway: Mouth to Snout -Cusp hands over mouth and blow into the nostrils of the pet. May not be that effective in brachycephalic breeds with stenoic nares -Least effective, but should be performed if nothing else is available Face mask over nose & Ambu Bag (bag mouth valve) -Room air is just as effective as oxygen 244

4 -Face mask must have tight fitting seal Intubation is the most effective -Place cuffed endotracheal tube with water-soluble gel on end to help form seal -Practice intubating pets on their side -Administer breaths with ambu bag -Ambu bag is preferred over anesthesia machine with reservoir bag due to the length of dead space between the reservoir bag/circuit to the patient Breathing Unlike human CPR, breaths are given simultaneously with compressions at a rate of 10 breaths per minute. If you are performing CPR all by yourself you should perform 30 compressions and then administer 2 breaths. If performed with at least one other person it should be 1 breath every 6 seconds (10 breaths a minute). To perform adequate breathing the patient's neck should be extended. Each breath should be for a full one second while someone watches to ensure the chest inflates the first few breaths. Breaths should only be one second long to ensure adequate ventilation. More frequent ventilation has been shown to decrease myocardial and cerebral perfusion and decreases the chance of spontaneous ventilation returning. Over-ventilation is one of the most common errors in veterinary medicine during CPR. While hyperventilation is a common problem it should be noted that hypoventilation will cause a decrease in perfusion to core organs (heart, brain, lungs). A rate of 10 breaths a minute (1 breath every 6 seconds) is key to adequate ventilation. CPR efforts can be monitored using end tidal CO 2 device. At the start of an arrest the EtCO 2 will read zero or near zero. With CPR efforts the EtCO 2 will increase with the onset of chest compressions and will increase more with the onset of ventilation. In humans, an EtCO 2 < 10 mm Hg over a period of several minutes during CPR is a poor prognostic indicator for ROSC. In an experimental canine study, the EtCO 2 increased from mm Hg during CPR to mm Hg at or just prior to ROSC. Impedance Threshold Device (ITD) In the past 5 years there has been much discussion on the use of impedence threshold devices. They work by increasing blood flow to the heart and brain during assisted ventilation. They increase coronary perfusion and increase blood flow during the next compression. They have been recommended as a circulatory enhancer by the American Heart Association (AHA) because they have been shown to increase the opportunity for survival and offer a better chance of a normal neurological outcome. More recent studies have shown that, while they may enhance the circulatory system during CPR, they do not demonstrate an increase in chance of survival. Unfortunately while the AHA recommends them for their use in people they do not appear to be effective when used in smaller animal patients. RECOVER states, "...because the device requires chest wall recoil to generate a cracking pressure of at least 12 cm H2O, use is not feasible in small dogs or cats weighing less than 10 kg because they are unlikely to be capable of generating those types of pressures from elastic recoil alone. Therefore, the use of an ITD to enhance circulation is reasonable in animals > 10 kg, but studies to date have not demonstrated a survival advantage with their use." In conclusion if an ITD is available it can be used, but it will likely not improve the CPR outcome. Some ITD devices have a light that flashes to give the person performing breaths a visual reminder to give the patient a breath. It is in this author's opinion that an ITD is a nice device to use during CPR because it takes the error out of when to breath. The person administering the breaths just waits for the light to blink and then administers a breath. CONCLUSION It is important to fully understand how to perform basic life support in order for the patient to have the best chance of survival. Practicing CPR drills and how to correctly perform chest compressions and ventilation will allow staff to be better prepared for the real thing. Poor performed compressions generate even smaller stroke volumes References Available Upon Request 245

5 CPR: ADVANCED LIFE SUPPORT Amy Newfield, CVT, VTS (ECC) BluePearl-Waltham, MA, USA Please note: The first set of veterinary specific CPR guidelines were published in June of 2012 by the RECOVER campaign in the Journal of Veterinary Emergency and Critical Care. (Special Issue: Reassessment Campaign on Veterinary Resuscitation: Evidence and Knowledge Gap Analysis on Veterinary CPR, June 2012, Volume 22, Issue s1, Pages i i, S1 S131) For more specific information on CPR in animals please go to where a link can be found to the guidelines. INTRODUCTION With in advances in veterinary medicine there are now a myriad of drugs that can be used during CPR. Drugs that use to be commonly used are no longer used. It can often get confusing as to what to use and when to use it. These notes will focus on advanced life support based on the RECOVER campaign. Readers should be encouraged to take the basic life support course and review the notes before proceeding onto the advanced. DEFIBRILLATION In order to use electrical defibrillation a fibrillating arrhythmia must be proven on ECG. It is important that all staff are aware of how to defibrillate a pet and how to use the machine as well has the protocols involved when defibrillation is about to occur. During CPR no rubbing alcohol should be placed on the ECG leads. While it is important to attach all pets to an ECG machine during CPR, gel only should be used in case the pet needs to be defibrillated. Failure to use gel only may cause a fire hazard or burning of the pet when the alcohol meets electricity. The appropriate amount of joules should be set (external defibrillation 4-6 J/kg internal defibrillation J/kg). It is important that the person is who going to be placing the charged paddles on the pet calls clear to indicate everyone must move away from the patient. Failure to do so may cause an electric current to be sent into any persons who are still touching the table or patient. It is easier to place patient in a trough to maintain stability. The pet may "jump" after the electrical current is administered which may cause them to fall off the stable if they are not stabilizes in a tough or with blankets around them. The precordial thump was fist described as a treatment option for ventricular fibrillation in a case report in 1969 and a case series in It is also known as mechanical defibrillation. In theory the defibrillation occurs by striking the patient with the heel of the hand directly over the heart in a forceful motion. If electrical defibrillation is not available it is a technique that can be attempted, but in this author's experience, rarely, if ever, is it effective. ROUTES OF ADMINISTRATION Intravenous is the preferred route when administering any drug during CPR. It is imperative that chest compressions and ventilation are not stopped for administration of drugs. An intravenous catheter should be placed to allow multiple injections of drugs during the CPR process. While most of the time a peripheral over-the-needles catheter will be placed in a leg, drugs will be absorbed faster if an over-the-needle catheter is placed in the jugular vein. This 246

6 may not be appropriate depending on the pet s condition, specifically if it has neck wounds or head trauma. Patient size and the fact that chest compressions are being administered (and should not be stopped) also are factors to whether placement of a catheter into the jugular vein is possible. Placement into a jugular vein will allow for the drugs to reach the heart the fastest. By placing a short over-the-needle catheter into a jugular, subsequent placement of longer central lines into the jugular may be diminished. Depending on the type of central line available, it may be possible place a true central line catheter through the existing over-the-needle catheter after the patient is resuscitated. This is usually the case with the Seldinger technique. Placing the guidewire through the over-the-needle catheter, removing the over-the-needle catheter and then proceeding as normal usually allows for a long-term central line to be placed. Unfortunately the area was usually not prepared aseptically so risk of infection may be increased. More commonly peripheral catheters are placed because of the availability of multiple limbs and the familiarity of these locations. It s important to note that drugs will typically take 1 to 2 minutes to reach the central circulation when given via a peripheral vein. They require significantly less time when given via central vein. In order to speed up delivery to the heart a small bolus of isotonic crystalloids (10-20mls) should be given after each drug injected. Short large gauge over-the-needle catheters allow for the fastest fluid and drug flow. If venous access cannot be obtained, then drugs may be administered via trachea. While not ideal lidocaine, epinephrine, atropine, naloxone, and vasopressin have all been shown to be absorbed from the trachea. The amount given is generally times higher than the IV dose and absorption times are slower. Drugs can be given this route, but attempts should continue to gain venous access. The American Heart Association (AHA) recommends intraosseous (IO) as the second route of choice if venous access cannot be obtained. Studies have shown that IO is as effective as central venous access. In veterinary medicine IO is typically reserved for neonates, puppies or kittens. While it may be just as effective as obtaining venous access via the jugular vein, it generally takes slightly longer to obtain IO access as opposed to venous access of a peripheral vein. If a large amount of emergency patients are seen, the facility should consider purchasing a hand-held IO drill (EZ-IO ). This will make placing IO catheters fast and easy (under 30 seconds to place an IO catheter) so that focus can be turned to actual administration of drugs and patient resuscitation. Intracardiac is never recommended because of the serious complications which can occur (laceration, arrhythmias). It would be more preferable to administer drugs into the trachea. DRUGS Intravenous Fluids: The current recommendations are to only use intravenous fluids when the arrest occurs because of a hypovolemic episode. Multiple studies in animals have shown that fluid administration in euvolemic pets is associated with decreased coronary perfusion pressure. There are many theories as to why including that IV fluid administration increases central venous pressure thus opposing blood flow to the coronary and cerebral circulation. Therefore, the current veterinary recommendations during CPR in euvolemic or hypervolemic is to give IV fluids slowly, just enough to keep the IV catheter patent. The fluid of choice in human medicine is 0.9% NaCl, while in veterinary medicine it is usually LRS. Several studies suggest that hypertonic saline may improve survival as compared with normal saline. This technique is also known as low-volume resuscitation and can 247

7 result in a rapid increase in osmotic pressure because they cause a shift of fluids from the interstitial space into the intravascular space in order to improve venous return and cardiac output. One dose equals 4xs the volume of isotonic saline so a much smaller volume is needed. Hypertonic crystalloids (7.5% NaCl) can be given at a rate of 4ml/kg over two minutes, and treatment with hypertonic crystalloids should not exceed 1-2 hours (many veterinarians suggest a 1-2 time initial use only). If interstitial dehydration or hypernatermia secondary to a free water deficit are present, the use of hypertonic solutions is contraindicated. The overall effect of hypertonic saline lasts for about 20 minutes. An infusion along with a crystalloid and/or colloid can be used for the effect to be sustained. Minimally crystalloids must be given after the hypertonic saline. Hypertonic saline is the fluid of choice when dealing with a patient that may have head trauma because it helps to reduce cerebral edema while increasing coronary pressure. Solutions containing dextrose should be avoided unless there is evidence of hypoglycemia because they have been implicated with increased morbidly and mortality. Body Temperature: The newest research has shown that cooling patients during CPR may actually increase survival. In human medicine ice/salt solutions have been formed to decrease the body temperature in people to 95 F. By decreasing the body temperature survival rates in human patients treated with the ice/salt mixture was 46.7% vs. 31% and the survival rates were significantly higher in those in whom CPR was initiated within 10 minutes of collapse, 59.1% vs. 29.4%. The theory is that the hypothermia reduces the ischemia/reperfusion injury effects of CPA. While veterinary medicine is just on the cusp of starting to use ice/salt solutions for therapeutic hypothermia there is no current recommendations for actively decreasing the body's temperature during CPA. It is currently recommended that permissive hypothermia is beneficial and may increase success rate of CPR. Therefore aggressive warming of patients during CPR is no longer recommended. If the patient is cold, do not attempt to rewarm. Oxygen: Oxygen (Fi02 40% or greater) should be administered quickly. Intubation is the most effective method to deliver a high concentration of oxygen. If intubation cannot be performed and breathing has ceased, then mouth-to-snout should be attempted. While the AHA recommends the use of oxygen they do not have a position on whether it is more effective than mouth-to-mouth room air resuscitation in people. Currently there is no data to support a better outcome during CPR if room air is used versus oxygen. The RECOVER campaign recommends: "In the absence of arterial blood gas data, the risks of hypoxemia likely outweigh the risks of hyperoxemia, and the use of an FiO2 of 100% is reasonable." In order for CPR to be effective both the heart and brain must remain appropriately oxygenated. Myocardial oxygen delivery is dependent upon myocardial blood flow and arterial oxygen content (CaO2). Cerebral perfusion depends on cardiac output and cerebral vascular resistance. Therefore oxygen should be a benefit and should be able to help with CPR. Unfortunately some studies have shown that excessive oxygen may predispose patients to increased concentrations of reactive oxygen species during states of 248

8 CPA, worsening tissue damage during CPR. How effective oxygen actually is remains unknown. Atropine: Atropine is a prototype antimuscarinic drug meaning it has the ability to block muscarinic receptors. Muscarinic receptors are a type of acetylcholine receptors found in all effector cells (cells of muscles, glands or organs that are capable of responding to a nerve impulse) of the parasympathetic nervous system. The heart is supplied with both parasympathetic and sympathetic nerves. The parasympathetic nerves (also known as the vagi) are mainly attached to the sinus and A-V nodes of the heart. When the vagi are stimulated they release acetylcholine at their vagal ending. Acetylcholine causes a decrease in the rate of the sinus node and it also decreases the excitability of the A-V junctional fibers thus decreasing the cardiac impulse to the ventricles. This is also known as a vagal response. Vagal stimulation slows the heart beat and excessive stimulation can stop it entirely. Atropine inhibits acetylcholine at postganglionic parasympathetic neuroeffector sites which helps to stop this effect. Atropine is given when vagal responses are thought to have occurred. Most bradycardia is responsive to atropine. The AHA has not taken any stance on administering atropine during asystole. They state No prospective controlled studies support the use of atropine in asystole or slow pulseless electrical activity arrest. Atropine falls under their class of indeterminate drugs meaning there appears to be no harm in giving it, but it also does not appear beneficial during asystole. The well known side effect of atropine is that it can induce a severe sinus tachycardia. During an arrest hypoxia has generally occurred. There is some theory that sinus tachycardia caused by atropine can cause increase oxygen demands to the myocardium which predispose the myocardium to fibrillate. Doses vary and atropine can be used both IV and intratracheally (IT). For patients just suffering respiratory arrest a small dose of mg/kg can be given IV. For severe bradycardias or asystole the dose ranges from mg/kg IV. Currently the RECOVER campaign recommends a dose of 0.04 mg/kg IV. Higher doses (0.1, 0.2, 0.4 mg/kg) have been associated with worse outcomes in an experimental study in dogs. Epinephrine & Norepinephrine: Epinephrine (also known as adrenaline) is the most common drug used in CPR. Both epinephrine and norepineprhine are produced when the sympathetic nerves of the adrenal medullae are stimulated. While the adrenal medullae produces both norepinephrine and epinephrine, in general 80% of the secretion is epinephrine and 20% is norepinephine. Both are considered adrenergic receptors. There are two types of adrenergic receptors: alpha and beta. Alpha receptors are responsible for vasoconstriction while beta receptors are responsible for vasodilation. Norepinephrine mainly excites alpha receptors, but also can excite beta to a lesser extent. Epinephrine will excite both equally. When they are released they tend to have the same effects on the organs as direct sympathetic stimulation does, except that the effects of the drugs last 5-10 times longer. Both will cause an increases heart rate, contractions of the blood vessels and dilation of air passages. While both these drugs appear to be similar there are some notable differences. Epinephrine has a greater effect on the beta receptors and therefore a greater effect on 249

9 cardiac stimulation. However, epinephrine causes only weak constriction of blood vessels, while norepinephrine causes much stronger constriction. Because norepinephrine produces more constriction it will increase the total peripheral resistance and arterial pressure. Epinephrine will only increase arterial pressure slightly, but will increase cardiac output more. Epinephrine s main effects come from its ability to affect the αadrenergic receptors thus causing and increase in coronary and cerebral perfusion pressure. Epinephrine is used during asystole or pulseless electrical activity. Asystole is the most common arrest rhythm in veterinary medicine which is why epinephrine is the most common drug used during CPR. Studies have shown that epinephrine can be absorbed IT, but the dose needs to be significantly higher (5-10 times) than IV to have any effect. AHA recommends that IT epinephrine be diluted in water or normal saline. Studies have shown that dilution with water instead of 0.9% saline may achieve better drug absorption. Epinephrine (1:1,000) can be given IT at a dose of mg/kg. There are low dose epinephrine or high dose epinephrine dose ranges. Epinephrine has been associated with producing an increase in myocardial demand and ventricular arrhythmias after resuscitation. The theory behind a low-dose epinephrine is that the myocardial effects will be minimized, but that the epinephrine will still be able to increase the coronary and cerebral perfusion pressure. In human medicine there are studies that prove the benefits of both low-dose and high-dose. AHA has not taken on a position on whether low dose or high dose is more effective. The RECOVER campaign recommends the use of low-dose epinephrine and states high-dose epinephrine may be considered after prolonged CPR. Either dose can be given every 3-5 minutes IV. Low dose of 1mg/ml can be administered at 0.01mg/kg IV. The high dose of 1mg/ml epinephrine can be administered at 0.1mg/kg IV) Norepinephrine has not had a lot of studies with regards to its use in CPA. Studies suggest that norepinephrine produces effects similar to epinephrine. There have been very few animal or human related studies. While RECOVER lists a dose for norepinephrine in the literature, they do not provide any recommendation of administrating it. According to AHA the only prospective human trial showed that there was no benefit to using norepinephrine compared with that of epinephrine. The dose is g/kg/min and is given as a constant rate infusion. Because of the long proven history with epinephrine, AHA still recommends epinephrine as its drug of choice. Vasopressin: Vasopressin is a relatively new CPR drug in veterinary medicine. It has been shown to be able to be absorbed via trachea. Vasopressin itself is an effective nonadrenergic vasopressor that causes peripheral, coronary and renal vasoconstriction. It significantly improves cerebral and myocardial blood flow because of its nitric oxide vasodilatatory effect. Nitric Oxide (NO) is a mediator of vasodilation in blood vessels. While it continues to be debated in people as to whether vasopressin is superior to epinephrine, there have been a couple of studies showing that it has been in animals. It has been shown that in an acidic and hypoxic environment (which occurs during asystole) vasopressin is still able to stimulate the V 1A receptors (a receptor that resides in the brain) which leads to vasoconstriction. Epinephrine has been shown to lose some of its vasopressor effects in such environments. 250

10 RECOVER states, "It has been studied as an alternative to epinephrine during CPR. There have been limited studies. One prospective observational study suggested a beneficial effect of vasopressin while a prospective trial in dogs found equivalent survival rates. The human literature is mixed large meta-analyses have failed to show any benefit (or detriment) to the use of vasopressin over epinephrine in CPR. Although further study is needed, the use of vasopressin (0.8 U/kg IV) as a substitute or in combination with epinephrine every 3 5 minutes may be considered." The dose of vasopressin is 0.8u/kg IV and can be used during asystole or pulseless electrical activity just like epinephrine. While epinephrine can be administered every 3-5 minutes during resuscitation the AHA and RECOVER campaign only recommends that vasopressin be substituted for the first or second epinephrine dose and then epinephrine should be administered after. Lidocaine 2%: The use of lidocaine is strictly limited to arrhythmias and has no benefit during CPA. It is most commonly used to treat ventricular arrhythmias including refractory ventricular fibrillation. It works by blocking sodium from entering into the myocardial cells, decreases conduction velocity and decreases tissue excitability. The dose is 2mg/kg slow IV/IO push over 1-2 minutes. Lidocaine can be used if amiodarone is not available, but it is not the first drug of choice for ventricular arrhythmias. Amiodarone: Amiodarone can be used to treat ventricular fibrillation. The AHA and RECOVER campaign recommends the use of amiodarone before the use of lidocaine. Intravenous amiodarone affects sodium, potassium, and calcium channels and also has α- and βadrenergic blocking properties. AHA recommends if for treatment of ventricular fibrillation or pulseless ventricular tachycardia that is not responsive to CPR or vasopressors. A study was performed in 2002 and compared amiodarone with lidocaine. It found that amiodarone improved rate of survival while lidocaine was associated with more asystole after defibrillation. While there have been little to no studies in veterinary medicine it is suggested that amiodarone be used for continued ventricular fibrillation after defibrillation. A dose of 5mg/kg can be given IV slowly over 10 minutes. Amiodarone can cause persistent hypotension if it is not diluted out as described in the package insert or if it is not given slowly. Magnesium: In dogs with severe hypomagnesemia lethal ventricular arrhythmias have been reports. It use to be given routinely to every patient that arrested in case they were suffering from a decrease in magnesium. Studies now show no increase in resuscitation when magnesium is routinely given during CPR. If a decreased magnesium is suspected due to a metabolic disturbance or disease process than the dose is 1-2gm/kg over 2 minutes. 10% Calcium: Years ago calcium was a common drugs used in CPR. The theory was that it worked to help improve cardiac contractility. However, excessive calcium has been implicated in causing reperfusion injury and myocardial and cerebral vasoconstriction. The AHA and RECOVER campaign does not recommend the use of calcium during CPR. However, much like hypomagnesemia, hypocalcemia itself can lead to cardiac arrest. Ideally hypocalcemia should be confirmed via bloodwork prior to any administration of 251

11 calcium. Minimally a disease process should have been diagnosed causing the high suspicion of hypocalcemia. It is also recommended to give calcium when the pet is experiencing severe hyperkalemia as administered calcium has been shown to help protect the heart against the side effects of hyperkalemia. Steroids: There are no studies showing the benefits of administering steroids during CPA. The RECOVER campaign states "Given the lack of compelling evidence of a beneficial effect and the potential for deleterious side effects from corticosteroids, especially in animals with poor perfusion, the routine use of corticosteroids during CPR is not recommended." Bicarbonate Administration: CPA patients will have severe metabolic acidemia. There have been a myriad of studies in dogs showing both good and bad outcomes when giving bicabonate during CPA. Given the evidence available, bicarbonate therapy after prolonged CPA of greater than minutes may be considered. A dose of 1 meq/kg of sodium bicarbonate can be given. CONCLUSION It is important to fully understand what drugs are available during CPR so that a decision can be made quickly. Selecting the right drugs for the patient and administering them quickly provides the best chance of survival. References Available Upon Request 252

12 THE GREAT COLLOID DEBATE: TO USE OR NOT TO USE Amy Newfield, CVT, VTS (ECC) BluePearl Veterinary Partners, Waltham, MA HOW COLLOIDS WORK The movement of fluid between compartments is regulated by both hydrostatic pressure and osmotic pressure. Most commonly fluid movement occurs because of a change in osmotic pressure through osmosis. This can occur from illness (parvovirus, sepsis, etc) or injury which causes a shift in the body s fluids due to damage to the endothelial barrier resulting in capillary leaking or from a flow alteration (shock). Colloid osmotic pressure (COP) is the pressure exerted by plasma proteins in a fluid. Crystalloid solutions (such as Lactated Ringer s Solution, 0.9% NaCl) do not contain colloids (particles with molecular weight greater than 30,000 Daltons) so they cannot contribute to COP. Colloids contain negatively charged large molecules which help to draw water and sodium to them. This helps to keep these solutions within the intravascular space and thereby increases COP. Most of the time colloids will be given with crystalloids to help maintain the balance between extracellular and intracellular fluids. Because they are made of primarily large molecules, the volume given is much less than that of crystalloids. It is important to note that colloids are not made up of 100% large molecules. Once it is administered to the patient the molecules are placed under pressure, hydrolysis and excretion and may fall apart into smaller particles. The administration of colloids versus crystalloids has been a continued debate in both human and veterinary medicine for this reason. Despite this argument, without question, colloids help to increase osmotic pressure better than crystalloids and have a more prolonged effect on volume expansion. The question in the last 2 years in veterinary medicine has been are they doing more harm than good? This debate applies to synthetic colloids. SYNTHETIC COLLOIDS Hydroxyethyl Starch: There are three types of hydroxyethyl starches: hetastarch, pentastarch and tetrastarch. Generally the difference between the three is the degree of substitution (the number of substituted glucose molecules divided by the number of glucose molecules present) and the molecular weight (hetastarch has the highest molecular weight, tetrastarch the lowest). Routinely the term hetastarch and HES are used interchangeably, which is incorrect. However, despite the numerous types of HES available, they all perform basically the same job. Most common trade names include: Hespan (a hetastarch), HAESteril and Pentaspan (both pentastarch) and Voluven, Vetstarch (both tetrastarchs). The molecular weight of hetastarch is 450,000 daltons and a COP of 33 mmhg. HES is an effective volume expander by increasing or maintaining serum oncotic pressure, but it is not possible to predict how much the pressure will be increased within a particular patient. Synthetic colloids have been shown in people to cause several adverse side effects including acute kidney injury, higher morbidity rates, prolonged hospitalization and coagulopathies. These studies have caused the use of synthetic colloids to drop dramatically in human medicine. With the lack of evidence based literature for veterinary patients, the human-based studies were brought over to the veterinary industry. This resulted in many facilities abandoning the use of synthetic colloids all together, including entire countries. Over the years there have been many studies showing that certain drugs react differently in animal patients than in human (theobromine, xylitol, ibuprofen, naproxen, etc) so it is reasonable to deduce that colloids do not react the same way in animal patients as they do in human patients. The question is are we seeing the same side effects that human medicine is seeing then using HES products in our veterinary patients? One of the most well-documented side effects to using HES is its coagulopathy. HES has been shown to decrease factor VIII (an essential blood clotting factor), cause both functional and morphological changes to platelets and decrease both Von Willebrand s factor (vwf) and plasma clotting factors. It appears mainly dose dependent and at high doses (>22ml/kg in dogs) coagulation problems are more likely 253

13 to occur. Once the product is discontinued the patient s values generally return to normal. The coagulopathy associated with HES is usually insignificant and only poses a problem in pets with prior coagulation issues or where surgery may be needed. Though not as common, anaphylactic reactions can occur (more commonly in the cat than the dog). Vomiting, fever and uritcaria (hives) have been reported. When administering to cats particularly, slow administration (over minutes) is important. The dose of most hydroxyethyl starches is very small. It is important to make sure that any hydroxyethyl starch is not overdosed as it can also lead to fluid overload quickly. The smaller the molecular weight (such as that of Vetstarch ) can likely be given at a higher rate than higher molecular weight HES products (Hespan ). Safe shock doses for most HES are ml/kg in the dog (given either rapidly or over 15 minutes) and in the cat, 5-15 ml/kg given over 15 minutes. The same dose is currently used for the tetrastarch Vetstarch. The constant rate infusion of most HES products is 1-2ml/kg/hr in the dog and cat (not to exceed 20ml/kg/hr in 24 hours in the dog or 10ml/kg/hr in a 24 hours in the cat). All classes of synthetic colloids have been associated with acute kidney injury though HES is the most cited. HES-associated acute kidney injury is not fully understood. It is thought that HES is taken up in to the renal interstitial system causing damage. HES has been shown to cause a swelling of proximal renal tubular cells within a few hours of administration. Changes to the cells and tubules are reversible once the product is discontinued, but several human patients have had to undergo dialysis to promote reversal. HES has been shown to cause allergic reactions including anaphylaxis in human patients. Tissue uptake of HES is both dose and timedependent. Pruritus in human patients has a delayed onset (typically 1 6 weeks postexposure) and it has been reported to last up to 24 months. There was some theory that lower molecular weight HES would cause less pruritus, but that claim appears unfounded. With all the evidence in human literature supporting coagulopathies, acute kidney injury and allergic reactions the use of HES has been challenged in medicine. That said it must still be asked are we seeing the same side effects in veterinary medicine and what evidence based medicine to we have to go on? HUMAN Studies of Note: 2013: Tetrastarch and gelatins: Critical Care Medicine. Conclusion: "In cardiac surgery patients, fluid therapy with perioperative administration of synthetic colloids carries a high risk of renal replacement therapy and is not more effective than treating with only crystalloids." Hetastarch: Brazilian Journal of Anesthesiology. Conclusion: "During hip arthroplasty, patients treated with hypervolemic hemodilution with hydroxyethyl starch 130/0.4 required less transfusion and presented lower infection rate compared to patients who received lactated Ringer." Hetastarch: Annals of Surgery. Studied use of HES following major surgery. Conclusion: "Administration of HES 130/0.4 reduced clot strength and perioperative hemorrhage increased by more than 50%, while administration of lactated Ringer's solution provoked an approximately 2.5 times greater positive volume balance at the end of surgery." Hetastarch: Current Opinion in Anesthesiology. Studied: Data on the use of waxy maize-derived 6% HES 130/0.4 vs potato-derived 6% HES 130/0.42. Conlcusion: "During early goal-directed therapy waxy maize-derived 6% HES 130/0.4 showed no evidence for harm and an improvement in microvascular blood flow. In addition, experimental data suggest that waxy maize-derived 6% HES 130/0.4 may have different biological effects compared to potato-derived 6% HES 130/0.42 with potentially reduced pulmonary inflammation." Hetastarch: The Cochrane Database of Systematic Reviews. Studied HES vs other fluids and effects on kidney function of 11,399 patients (one of the largest). Conclusion: "The current evidence suggests that all HES products increase the risk in acute kidney injury and renal replacement therapy in all patient 254

14 populations and a safe volume of any HES solution has yet to be determined. In most clinical situations it is likely that these risks outweigh any benefits, and alternate volume replacement therapies should be used in place of HES products." 2012: Hetastarch: Intensive Care Medicine, Conclusion: "The quality and quantity of data evaluating 6 % hydroxyethyl starch (130/0.4 and 130/0.42) as a resuscitation fluid has increased in the last 12 months. Patients randomly assigned to resuscitation with 6 %HES 130 are at a 1.7% increase risk of being treated with renal replacement therapy." Hetastarch: The Cochrane Database of Systematic Reviews. Studied HES, Albumin, Gelatins and Dextrans for fluid therapy to see if one had more risk than the other. Conclusion: "From this review, there is no evidence that one colloid solution is more effective or safe than any other, although the confidence intervals were wide and do not exclude clinically significant differences between colloids. Larger trials of fluid therapy are needed if clinically significant differences in mortality are to be detected or excluded." 2004: Colloids vs. Crystalloids: The Cochrane Database of Systematic Reviews. Conclusion: "There is no evidence from randomized controlled trials that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery. As colloids are not associated with an improvement in survival, and as they are more expensive than crystalloids, it is hard to see how their continued use in these patients can be justified outside the context of randomized controlled trials." VETERINARY Studies of Note: JAVIM 2014: Cardiovascular, colloid osmotic pressure, and hemostatic effects of 2 formulations of hydroxyethyl starch in healthy horses. Conclusion "Both tetrastarch and hetastarch resulted in more effective volume expansion and arterial pressure support than normal saline. Tetrastarch produced a more sustained effect on COP with shorter duration of adverse effects on platelet function than hetastarch." Veterinary Anesthesia and Analgesia 2013: Study: Effects of 6% hetastarch (600/0.75) or lactated Ringer's solution on hemostatic variables and clinical bleeding in healthy dogs anesthetized for orthopedic surgery. Conclusion: "At the doses administered, both hetastarch and LRS can alter hemostatic variables in healthy dogs. However, in these dogs undergoing orthopedic surgery, neither fluid was associated with increased clinical bleeding." American Journal of Veterinary Research 2013: Effect of hydroxyethyl starch 130/0.4 and 200/0.5 solutions on canine platelet function in vitro. Studied: Blood samples were diluted 1:9 and 1:3 with 6% HES 130/0.4 and 10% HES 200/0.5 solutions and saline (0.9% NaCl) solution. Dilutions at 1:9 and 1:3 mimicked 10 ml/kg and 30 ml/kg doses. Conclusion: 1:3 dilution of blood samples from healthy dogs with HES 200/0.5 but not HES 130/0.4 significantly increased closure time beyond the dilutional effect, suggesting that IV administration of HES 200/0.5 in dogs might cause platelet dysfunction. A 19 page clinical practice review article was published in JVECC, Vol 24, Num 6, Nov/Dec 2014, Pages: Hydroxyethyl Starch: A review of pharmacokinetics, pharmacodynamics, current products and potential clinical risks, benefits and use. It concluded that extrapolation of data from human studies to small 255