ANESTHESIA OF THE PEDIATRIC PATIENT Victoria M. Lukasik, DVM, DACVAA Puppies and kittens are considered neonates until 4 to 5 weeks of age and are classified as pediatric until about 12 weeks old. Anesthesia of neonates may be necessary for urgent correction of congenital anomalies or for necessary (not elective) diagnostics. Anesthesia of pediatric patients may be undertaken for elective early ovariohysterectomy or castration or for urgent procedures. The physiology of neonates and pediatric patients is different in several ways compared to adult dogs and cats. These differences need to be understood to formulate optimal anesthetic plans that incorporate balanced drug combinations and appropriate dosing of those drugs. Post operative analgesia for elective procedures and peri-operative analgesia for urgent situations are a very important part of the anesthetic experience because a life long oversensitivity (allodynia) can develop if pain in neonatal and pediatric patients is not managed appropriately. Studies in infant boys undergoing circumcision indicate that sensitivity to pain can be precipitated at even a few days of age if proper analgesia is not provided.

THERMOREGULATION Smaller size, minimal fat reserves, and a higher body surface area to mass ratio all contribute to the development of hypothermia during the entire peri-anesthetic period. Of the three most common anesthetic complications (hypothermia, hypotension, hypoventilation), hypothermia is the easiest to document without the aid of expensive equipment. All that is needed is a hand held thermometer. Rectal temperature is usually 1 to 2 F lower than core temperature due to loss of muscle tone. It may be lower during procedures that expose the peri-rectal tissues: caudal abdominal, perineal, etc. Tympanic membrane temperatures can be very accurate because the middle ear shares the same vascular supply as the hypothalamus. However, ear thermometers can be technically challenging to use properly in most species. Esophageal readings reflect the temperature of the great vessels. Other methods of monitoring temperature: oral, axillary, and skin surface may not be accurate. Skin surface temperature rises and falls with the environmental temperature. Core body temperature is closely regulated by the hypothalamus; however, this regulation is immature and inefficient in pediatric patients. There are three tissue layers designed to insulate the body and prevent heat loss. These consist of the skin,

subcutaneous fat, and hair. These layers are more or less efficient in different patients depending upon their thickness. Overall, most pediatric patients lack thickness in all three layers. Heat transfer through the insulating layers and to the environment occurs in two stages. In stage one heat, is transferred from the core to the skin. In stage two, heat is lost to the environment by radiation, conduction, convection, and evaporation. Awake animals have several reactions to cold. Behavioral reactions include seeking

shelter

and

curling

up.

Physiologic

reactions

include

piloerection,

vasoconstriction, and shivering. Piloerection increases the depth of insulation by forming a stagnant layer of air around the animal. Vasoconstriction of the skin arterioles and arteriovenous anastamoses limits heat loss from the extremities. Shivering increases heat production in all muscle groups. There is also a chemical excitation for heat production which includes the release of epinephrine, norepinephrine, and thyroxin. Pediatric patients lack the ability to effectively respond to cold using physiologic mechanisms. The anesthetic drugs affect the thermoregulatory center and all compensatory reactions are further blunted or abolished. Causes of inadvertent hypothermia include general anesthesia: all anesthetics decrease the threshold for thermoregulatory vasoconstriction, basal metabolic rate is decreased, muscle tone is decreased, operating room temperature is often well below body temperature, skin prep solutions at room temperature and evaporation, cold irrigation solutions at room temperature and evaporation, IV fluids at room temperature, exposed serous surfaces: evaporation, prolonged surgical procedures: patients become more unstable and continue to cool as anesthesia time increases, and patients becomes wet during anesthesia: urine, flush, or bathed. All pediatric patients should be kept normothermic pre-operatively, during anesthesia and post-operatively. Post-operative shivering will increase oxygen consumption by as much 200% to 600% at a time when lung and circulatory function may not be optimal. Post operative shivering also increases intraocular pressure, increases intracranial pressure, and increases wound pain. Hemorrhage may be increased by the disruption of clots. Carbon dioxide production is greatly increased and may cause acidemia. Ventilation may be decreased, leading to hypoxemia (tissue hypoxia). Hypothermia must be differentiated from post-operative pain, which may also cause shivering. The prevention of inadvertent hypothermia is more desirable than trying to rewarm patients once they become cold. Effective re-warming cannot happen unless at

least 60% of body surface area is in contact with an external heat source. Desirable methods

for

preventing

inadvertent

hypothermia

include

controlling

ambient

temperature: keep the OR temperature at least 75 F, insulate patients using bubble wrap, plastic wrap, or warm blankets, warm skin prep and irrigation solutions, warm all intravenous fluids, humidify and heat inspired gasses by using an “artificial nose” like the HumidVent, use of a heated breathing circuit (Darvall Heated Breathing System), use circulating hot water blankets at 105 to 107 F, forced air heat exchange blanket like the Bair Hugger, and keeping patients dry or actively dry them post-operatively: hand held blow dryer. There are other available methods for providing an external heat source, but they are not desirable due to the potential for thermal injury or electrocution. Radiant heaters or heat lamps (“French Fry” lamps) cannot be easily regulated and can cause severe thermal injury to the skin. Electric heating pads and electric heating boards can develop hot spots or become wet and shock/electrocute a patient. Hot water bottles can be used provided that they are not above 107 F and are removed when they become cool. It is important to monitor a patient’s temperature closely due to the possibility of overshoot. Hyperthermia during surgery or re-warming can occur because the blood vessels in the periphery are vasodilated due to the anesthetic drugs. Heat is easily transferred to the core when peripheral vessels are vasodilated. The adverse effects of hyperthermia are also numerous and can be detrimental to a patient’s well being. CARDIOVASCULAR AND PULMONARY PHYSIOLOGY With the first breath of life, a profound and necessary change in circulatory physiology takes place. Expansion of the pulmonary tissues by inflation of the alveoli creates the supportive structure necessary for pulmonary circulation to occur. Pulmonary vascular resistance decreases dramatically and the exchange of oxygen and carbon dioxide by the lungs commences. There is a much higher metabolic demand for oxygen in the first few weeks of life, approximately three times greater compared to adults. An increased respiratory rate helps to meet this increased demand for oxygen. Any decrease in respiratory rate or depth, which is very common during anesthesia, will have an effect upon tissue oxygenation.

Cardiac output is dependant upon heart rate.

Induced bradycardia may profoundly affect cardiac output and blood pressure. Increases in preload and afterload are poorly tolerated and blood loss as little as 5 ml/kg can precipitate profound hypotension. Hematopoesis does not effectively begin until two to

three months of age, further limiting the pediatric patient’s ability to withstand hemmorhage. Blood loss needs to be prevented by adequate surgical hemostasis or treated aggressively before severe physiologic insult occurs due to tissue hypoxia. PREPARATION FOR GENERAL ANESTHESIA Pediatric patients have minimal glycogen stores in the liver and should be minimally fasted. Approximately two to four hours off of food is sufficient for gastric emptying. Water should be withdrawn when the pre-medication is given. Laboratory ttesting for young, healthy patients should include a packed cell volume (PCV), total plasma solids (TPS), blood urea nitrogen (BUN), and blood glucose. All of these tests can be accomplished with minimal equipment and time. This minimale laboratory evaluation is designed to aid in the recognition of disease processes not related to the surgical problem. Premedication with a balanced drug combination is the most desirable. Combining drugs from different classes will enable individual drug doses to be reduced, limiting unwanted side effects while still providing optimal stress reduction and preemptive analgesia. After premedication, patients should be placed in a quiet environment and be observed, but undisturbed, until maximal drug effects have occurred. This may be as long as 60 minutes after SQ injection. The environmental temperature in the pre-surgical holding area should be relatively warm or an external heat source should be supplied because hypothermia is common after sedation. The patient should also be placed on towels or shredded paper to absorb urine or feces. It is important to have all necessary drugs and equipment ready in advance. This includes the appropriate breathing circuit, correct size endotracheal tube and reservoir bag, changing CO2 absorbent if necessary, leak checking the anesthesia machine, and ensuring an adequate oxygen and liquid anesthetic supply. Being prepared for any complication before drug administration is the key to a successful anesthetic. In general, non-rebreathing circuits (Bain, Norman elbow, Jackson-Reese, Ayers T-piece, etc.) are recommended for patients with lean body weights less than 5 kg (11 pounds) and rebreathing or circle systems (Wye, Pediatric Wye, Universal-F, etc.) are used in patients weighing more than 5 kg (11 pounds). Pre-induction support should include pre-oxygenation via facemask, IV fluids, pre-emptive analgesia, external heat source, and proper padding. Removing the rubber diaphragm from the mask may prevent some of the resistance to it.

INDUCTION TO GENERAL ANESTHESIA General anesthesia is a reversible process that induces immobilization, muscle relaxation, unconsciousness, and freedom from pain. Induction of general anesthesia in pediatric patients is best accomplished may be accomplished using injectable drugs, rather than or by the administration of inhalant anesthetic by facemask. In general, Iinjectable inductions are preferred because they allow a more rapid loss of consciousness, produce less patient struggling, enable earlier control of the airway, and pose less danger of physical injury to the patient and staff. There are many drugs available for IV anesthetic induction. Popular drugs for IV induction include propofol, alfaxalone, etomidate and the combination of midazolam and ketamine. Propofol is a short acting hypnotic that is unrelated to other general anesthetic drugs. Propofol’s onset of action is within seconds and the duration of effect of a single bolus is 2 to 5 minutes. Induction is usually smooth; however muscle twitching can occur. The incidence of muscle twitching can be reduced if midazolam or diazepam are administered IV prior to propofol induction. Propofol is rapidly metabolized and has NO analgesic properties. Some adverse effects of propofol include apnea, especially with rapid administration, hypotension, bradycardia or tachycardia, and decreased cardiac output by as much as 50%. Repeated administration may cause Heinz body production in cats. Propofol should be used with caution in patients with decreased cardiac reserve. Propofol’s cardiopulmonary effects are similar to those of thiopental (Pentothal). Alfaxalone (Alfaxan®, Jurox Pty Limited; Rutherford NSW, AU) is an anesthetic induction drug approved for use in dogs and cats. It is classified as a neuroactive steroid and exerts its mechanism of action by modulating neuronal cell membrane chloride ion transport by binding to GABAA cell surface receptors. Alfaxalone is administered slow and steady to effect over about 60 seconds. Induction doses are between 1 and 2 mg/kg IV in dogs and between 3 and 4 mg/kg IV in cats. Alfaxalone can be administered as intermittent boluses or a CRI for maintenance of anesthesia. Alfaxalone can depress cardiorespiratory function in a dose dependent manner. It has also been administered IM in combination with other sedatives and analgesics to successfully sedate fractious patients. Etomidate (Amidate) is an imidazole derivative whose mechanism of action is not fully understood. Etomidate has NO analgesic properties. Analgesia must be provided for invasive procedures. Etomidate has little to no effect upon myocardial metabolism, cardiac output, peripheral circulation, or pulmonary circulation, but it may

depress ventilation slightly. It is supplied in a propylene glycol base therefore rapid IV injection may cause hemolysis. Reduced plasma cortisol and aldosterone levels have been reported for up to six hours after etomidate administration. The combination of diazepam or midazolam and ketamine will induce anesthesia within 30 to 60 seconds. The duration of a single bolus is approximately 2 to 5 minutes. Intubation is slightly different because laryngeal reflexes are maintained. Patients may also exhibit salivation, apnea, and muscle stiffness, especially with a 1:1 volume ratio of diazepam:ketamine. Propofol (Diprivan) is a short acting hypnotic that is unrelated to other general anesthetic drugs. Propofol’s onset of action is within seconds and the duration of effect of a single bolus is 2 to 5 minutes. Induction is usually smooth; however muscle twitching can occur. The incidence of muscle twitching can be reduced if midazolam or diazepam are administered IV prior to propofol induction. Propofol is rapidly metabolized and has NO analgesic properties. Some adverse effects of propofol include apnea, especially with rapid administration, hypotension, bradycardia or tachycardia, and decreased cardiac output by as much as 50%. Propofol should be used with caution in patients with decreased cardiac reserve. T The combination he author prefers a 2:1 volume ratio of midazolam:ketamine dosed at 0.5 to 1 ml/10 kg (midazolam 0.165 to 0.33 mg/kg and ketamine 1.65 to 3.3 mg/kg) to reduce muscle stiffness. Ketamine causes a central release of catecholamines resulting in tachycardia, increased cardiac output, and increased blood pressure. In catecholamine depleted patients, ketamine will act as a direct myocardial depressant and decrease cardiac output. Induction using inhalant anesthetics delivered by facemask is less desirable than IV inductions. It is a relatively slow process that is stressful to the patient and staff. Even inductions with sevoflurane usually take about six minutes compared to between 30 and 60 seconds with an injectable induction. There is also a greater potential for injury to patient and staff. The large amount of oxygen and liquid anesthetic used produces copious amounts of waste anesthetic gas increasing staff health risks and significantly increasing cost. There is little documented hard evidence against mask inductions in cats. However, an equine mortality study definitely shows an increased risk of death associated with inhalant anesthetic induction. This study reports nearly a three-fold higher risk of death with inhalant induction compared to injectable induction. The concentration of inhalant necessary for intubation is much higher than that needed for surgical incision. This generally means that by the time a patient is deep

enough with gas to intubate, they will likely be VERY hypotensive and respiratorydepressed. Patients with pre-existing cardiovascular compromise or those that lack organ reserve due to illness are at great risk of decompensation and can experience catastrophic complication.

Immediately followingfollowing

anesthetic induction, the endotracheal tube is

placed and cuff inflated. Over-inflation of the endotracheal tube cuff may cause because tracheal crush injury or tracheal rupture. The patient’s respiratory rate, heart rate and rhythm, MM color, CRT, arterial blood pressure, ECG, ETCO2, and temperature should be should be checked immediately after anesthetic induction and at five minute no longer than 5 minute intervals throughout anesthesia. MAINTANENCE Most patients are maintained on inhalant anesthetics and they are preferred to injectable drugs in pediatric dogs and cats. The most commonly used inhalant anesthetics are isoflurane and sevoflurane. All of the inhalant anesthetics cause cause some degree of vasodilation, hypotension, myocardial depression, and respiratory depression. Other adverse effects include nausea, vomiting, ileus, and cardiac arrhythmias. These inhalant anesthetics undergo very little hepatic metabolism. Elimination is via the lung, so awakening is usually rapid after discontinuing inhalant administration. Patients maintained on sevoflurane experience less respiratory depression compared to isoflurane when breathing spontaneously.

RECOVERY Patients need to be supported and monitored in the post-operative period. It is also vitally important to provide appropriate analgesia. The administration of analgesics to pediatric patients is often overlooked or inappropriately under dosed. Analgesic protocols should be devised based upon the invasiveness of the surgical procedure and the anticipated degree of pain postoperatively. Analgesics should be provided for a minimum of 48 to 72 hours.

PREMEDICATION Balanced premedication combinations usually include one drug from each group based upon individual patient needs. Group Drug Dose Route Comments

Anticholinergics

Glycopyrrolate

0.005 – 0.01

Does not cross bloodbrain barrier Atropine 0.01 to 0.04 IM, IV Therapy for profound bradycardia Tranquilizers Midazolam 0.1 to 0.4 IM, IV IM uptake rapid and complete Diazepam 0.1 – 0.4 IV IV only, IM uptake not reliable Xylazine Not Not in patients less recommended than 12 weeks of age Dexmedetomidine Not Not in Patient’s less recommended than 12 weeks of age Acepromazine Not Not in patients less recommended than 8 weeks or in dehydration Opioid Analgesics Morphine 0.05 – 0.25 IM Emesis common Hydromorphone 0.03 – 0.075 IM, IV Good analgesic Oxymorphone 0.03 – 0.075 IM, IV Good analgesic Buprenorphine 0.01 – 0.05 IM For mild pain only Butorphanol 0.4 to 0.6 IM, IV Very poor analgesia, good sedative properties INDUCTION DRUGS Drug(s) Dose mg/kg Route Comments Propofol 1–4 IV Apnea and hypotension common Diazepam/Ketamine 0.15-0.3/1.5-3 IV Retain laryngeal reflexes Etomidate 1-2 IV Good in unstable cardiac patients REVERSAL DRUGS Drug Flumazenil Atipamezole Naloxone

Dose mg/kg 0.01 0.2 0.01 to 0.02

Route IV IM IM, IV

IM, IV

Drug Class Reversed Benzodiazepines Alpha-2 Agonists Opioids: all analgesia reversed