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81st Western Veterinary Conference

V238
Neonatal Resuscitation: Techniques to Improve Outcome Autumn Davidson, DVM, MS, DACVIM University of California-Davis, Davis, CA, USA
OBJECTIVES OF THE PRESENTATION This presentation will review the techniques to improve diagnostics and therapeutics used to improve neonatal survival. KEY CLINICAL DIAGNOSTIC POINTS Prudent veterinary intervention in the prenatal, parturient and postpartum periods can increase neonatal survival by controlling or eliminating factors contributing to puppy and kitten morbidity and mortality. KEY ETIOLOGIC AND PATHOPHYSIOLOGIC POINTS About half of all puppies and kittens that fail to survive to weaning are stillborn or die within the first three days of life. Factors implicated in perinatal deaths include prematurity, in utero infection with viruses such as canine distemper, canine parvovirus, feline herpes, feline infectious peritonitis, panleukopenia, and feline leukemia virus, anatomic birth defects (found in about 10% of non surviving neonates), birth trauma, inadequate nutrition, maternal neglect, and environmental stresses. Optimal husbandry impacts neonatal survival favorably by managing labor and delivery to reduce stillbirths, controlling parasitism and reducing infectious disease, preventing injury and environmental exposure, and optimizing nutrition of the dam and neonates. Proper genetic screening for selection of breeders minimizes inherited congenital defects. A low birth weight is the most significant risk factor for neonatal puppy and kitten death. Birth weights of puppies are breed dependent, the average birth weight of surviving kittens is 100 g 10 g, and they typically gain 90100 g/week for the first 6 weeks of life. Wasting and non surviving puppies and kittens may be smaller at birth with reduced weight gain or even weight loss. The cause of low birth weight or poor growth is usually difficult to determine but may include immaturity, inborn errors of metabolism, birth defects, infections, nutritional deficiencies, and maternal neglect. Risk of neonatal loss was also associated with obese dams, singleton litters, and for the first neonate born in a litter. A higher rate of death of the first neonate born suggests that the dam may not care for her first born as readily as the following offspring. Some dams may not allow nursing until the delivery of the entire litter is complete, thereby subjecting the first born to delayed milk intake. Extended or difficult labor may result in birth trauma, in neonates that are too weak to nurse, or in ill or exhausted dams that are unable to care for their offspring. KEY THERAPEUTIC POINTS
Neonatal Resuscitation

Optimal neonatal resuscitation following birth (if the dam fails to do so) or caesarean section involves the same A-B-Cs as any cardiopulmonary resuscitation. First, prompt clearing of airways (A) by gentle suction with a bulb syringe, and drying and stimulation of the neonate to promote respiration (B), and avoid chilling are performed. Neonates should not be swung to clear airways as described in the veterinary literature, because of the potential for cerebral hemorrhage from concussion. The use of doxapram as a respiratory stimulant is unlikely to improve hypoxemia associated with hypoventilation, and is not recommended. Spontaneous breathing and vocalization at birth are positively associated with survival through 7 days of age. Intervention for resuscitation of neonates following vaginal delivery should take place if the dams actions fail to stimulate respiration, vocalization and movement within one minute of birth. Cardiopulmonary resuscitation for neonates who fail to breathe spontaneously is challenging yet potentially rewarding. Ventilatory support should include constant flow O2 delivery by facemask. If this is ineffective after one minute, positive pressure with a snugly fitting mask or endotracheal intubation

and rebreathing bag (using a 2-mm endotracheal tube or a 12 to 16- gauge intravenous catheter) is advised. Anecdotal success with Jen Chung acupuncture point stimulation has been claimed when a 25gauge needle is inserted into the nasal philtrum at the base of the nares and rotated when bone is contacted. Cardiac stimulation (C) should follow ventilation support, as myocardial hypoxemia is the most common cause of bradycardia or asystole. Direct trans-thoracic cardiac compressions are advised as the first step; epinephrine is the drug of choice for cardiac arrest/standstill (0.2 mg/kg administered best by the intravenous or intraosseous route). Venous access in the neonate is challenging, the single umbilical vein is one possibility. The proximal humerus, proximal femur and proximomedial tibia offer intraosseous sites for drug administration. Atropine is currently not advised in neonatal resuscitation. The mechanism of bradycardia is hypoxemia-induced myocardial depression rather than vagal mediation, and anticholinergic induced tachycardia can actually exacerbate myocardial oxygen deficits.
Beyond The ABCs

Chilled neonates can fail to respond to resuscitation. Hypothermia occurs when the body temperature is less than 94F or 34.4C. Loss of body temperature occurs rapidly when a neonate is damp. Keeping the neonate warm is important during resuscitation and in the immediate post partum period. During resuscitation, placing the chilled neonates trunk into a warm water bath (9599F, 3537.2C) can improve response. Working under a heat lamp or within a Bair hugger warming device is helpful. Post resuscitation, neonates should be placed in a warm box (a Styrofoam picnic box with ventilation holes is ideal) with warm bedding until they can be left with their dam. Neonates lack glucose reserves and have minimal capacity for gluconeogenesis. Providing energy during prolonged resuscitation efforts becomes critical. Clinical hypoglycemia involves blood glucose levels less than 30 to 40 mg/dl, and can be treated with dextrose solution intravenously/intraosseously, at a dose of 0.5 to 1.0 g/kg using a 5 to 10% solution; or a dose of 2 to 4 ml/kg of a 10% dextrose solution. Single administration of parenteral glucose is adequate if the puppy can then be fed or nurses. Fifty percent dextrose solution should only be applied to the mucous membranes because of the potential for phlebitis if administered intravenously; however, circulation must be adequate for absorption from the mucosa. Oral 1020% dextrose can be administered at 1 ml/100 g bw per hour until the neonate is stronger and normoglycemic. Neonates administered dextrose should be monitored for hyperglycemia because of immature metabolic regulatory mechanisms. If a neonate is too weak to nurse or suckle, a mixture of a warmed, balanced crystalloid (lactated ringers solution or normosol solution and 5% dextrose may be administered subcutaneously at a dose of 1 ml per 30 g of body weight, until the pup can be fed or nurses. A balanced warmed nutrient-electrolyte solution can be administered orally by stomach tube every 1530 minutes until the neonate is capable of suckling.
When To Stop Resuscitation

1. 2.

No response after 1520 minutes of effort (continued agonal respiration, bradycardia). Serious congenital defect detected (cleft palate, loud murmur, gastroschisis, large omphalocele, large fontanel).

Husbandry: The First Days

Post resuscitation or within the first 24 hours of a natural delivery a complete physical examination should be performed by a veterinarian, technician or knowledgeable breeder. The oral cavity, haircoat, limbs, umbilicus and urogenital structures should be visually inspected. The mucous membranes should be pink and moist, a suckle reflex present, the coat full and clean, the urethra and anus patent. A normal umbilicus is dry without surrounding erythema. The thorax should be ausculted; vesicular breath sounds and a lack of murmur are normal. The abdomen should be pliant and not painful. A normal neonate will squirm and vocalize when examined, nurse and sleep quietly when returned to the dam. Normal neonates will attempt to right themselves and orient by rooting toward their dam. Neonates are highly susceptible to environmental stress, infection and malnutrition. Proper husbandry is critical and should include daily examination of each neonate for vigor and recording of weight.

Warmth

Puppies and kittens lack thermoregulatory mechanisms until four weeks of age, thus the ambient temperature must be high enough to facilitate maintenance of a body temperature of at least 97 degrees F (36C). Hypothermia negatively impacts immunity, nursing and digestion. Exogenous heat should be supplied, best in the form of an overhead heat lamp. Heating pads run the risk of burning neonates incapable of moving away from excessively hot surfaces. Chilled neonates must be re-warmed slowly (30 minutes) to avoid peripheral vasodilation and dehydration. Tube feeding should be delayed until the neonate is euthermic, hypothermia induces ileus and regurgitation and aspiration can result. Neonatal normal body temperature (rectal): Week 1 9599F 3537.2C Week 23 97100F 36.137.7C At weaning: 99101F 37.238.3C Environmental warmth required: Wk 1: 8489F 28.931.6C Wks 2/3: 80F 26.6C Wk 4: 6975F 20.523.9C Wk 5: 69F 20.5C
Groceries

Neonates have minimal body fat reserves and limited metabolic capacity to generate glucose from precursors. Glycogen stores are depleted shortly after birth, making adequate nourishment from nursing vital. Even minimal fasting can result in hypoglycemia. Hypoglycemia can also result from endotoxemia, septicemia, portosystemic shunts and glycogen storage abnormalities. Oral fluid and glucose replacement may be preferable if the puppy has an adequate swallowing reflex and is not clinically compromised. The canine neonatal caloric requirement is 133 calories/kg/day during the first week of life, 155 calories/kg/day for the second, 175198 calories/kg/day for the third and 220 calories/kg/day for the fourth. Kittens require approximately 20 kcals ME/100 g bw/day. Commercially manufactured milk replacement formulas (EsbilacPet-Ag Inc, Elgin, IL; Puppy Milk Replacer Formula: Eukanuba, The Iams Co, Dayton OH; Veta-Lac Powder for Puppies: Vet-A-Mix, Shenandoah, IA, KMRPet-Ag Inc, Elgin IL) are usually superior to homemade versions. The use of milk obtained from the dam can be considered if available. An osmotic diarrhea (usually yellow, curdled stool appearance) can result from overfeeding formula, necessitating diluting the product 50% with water or a balanced crystalloid such as lactated ringers solution. The water requirement is 180 ml/kg/day. Tube feeding may be necessary in weak neonates, the gastric volume is approximately 4 ml/100 g bw. Feeding should occur every 24 hours. Neonates should gain weight steadily from the first day after birth (a transient mild loss from birth weight is acceptable on day 1); puppies gaining 13 grams per day per pound (2.2 kg) of anticipated adult weight and kittens 50100 grams weekly. Neonatal weights should be recorded daily for the first two weeks, then every 3 days until a month of age. Healthy well nourished neonates are quiet and sleep when not nursing. Normal neonatal weight gain: Increase of 510 % body weight per day.
Orphans Special Needs

Kittens and puppies under 3 weeks of age lack voluntary elimination and must have the micturition and defecation reflexes stimulated using a cotton ball with mineral oil on the anogenital area. Sibling suckling can cause dermatologic lesions, periodic separation of the neonates in an orphaned litter may be necessary until solid food is introduced.
Immunity

Incompletely developed immune systems during the first 10 days of life make neonates vulnerable to systemic infection (most commonly bacterial and viral). Adequate ingestion of colostrum must occur promptly post partum for puppies to acquire passive immunity. The intestinal absorption of IgG generally ceases by 24 hours after parturition. Colostrum deprived kittens given adult cat serum at a dose

of 150 ml/kg sc or ip developed serum IgG levels comparable with suckling littermates, however colostrum deprived puppies given 40 ml/kg adult dog serum orally and parentally failed to match suckling littermates IgG levels. Neonates should be encouraged to suckle promptly after resuscitation is completed; this usually necessitates close monitoring after a caesarean section as the dam is still groggy from anesthesia. Maternal instincts (protecting, retrieving, grooming, nursing) usually return within 24 hours.
Neonatal Medicine

Neonatal Sepsis While congenital, nutritional, and environmental factors are the most common contributors to perinatal morbidity and mortality, bacterial infection plays a larger role in apparently healthy puppies and kittens that fade after the first week of life. It is interesting that in a large survey of 95 specific pathogen free kittens that failed to survive to weaning, only one died after one week of age, while a much higher proportion of kittens died after one week in purebred catteries. This suggests that infection takes a significant toll on kittens reared in conventional settings. The incubation period of various infections accounts for the delay in clinical signs observed following exposure. Typically, an entire litter is affected by the same infection. Thus, it is imperative to perform complete necropsies with microbial culture and sensitivity testing on dead neonates to enable appropriate treatment of the remaining littermates. Although viruses and protozoa claim some neonates during this period, bacterial infections are the most common. At the time of birth, the neonate leaves its sterile uterine protection and enters an environment crowded with bacteria. The neonates defense against overwhelming bacterial colonization is primarily nonspecific innate immunity and passively acquired maternal antibody. Neonates with failure of passive transfer are especially susceptible to bacterial sepsis. The most common bacterial pathogens cultured from septicemic neonates of this age range are Streptococcus canis and gram-negative enteropathogens. The umbilicus of neonates should be treated with tincture of iodine immediately after birth to reduce contamination and prevent ascent of bacteria into the peritoneal cavity (omphalitis-peritonitis). Neonatal bacterial septicemia can cause rapid deterioration resulting in death if not recognized and treated promptly. Factors that reportedly predispose a neonate to septicemia include endometritis in the dam, a prolonged delivery/dystocia, feeding of replacement formulas, the use of ampicillin, stress, low birth weight (< 350 g for a medium size canine breeds, < 100 g for kittens), and chilling with body temperature < 96 degrees F (35,5 C). The organisms most frequently associated with septicemia are E.coli, streptococci, staphylococci, and Klebsiella spp. Pre-mortem diagnosis can be challenging, clinical signs may not be noted due to sudden death. Commonly, a decrease in weight gain, failure to suckle, hematuria, persistent diarrhea, unusual vocalization, abdominal distension and pain, and sloughing of the extremities indicate septicemia may be present. Prompt therapy with broad spectrum, bactericidal antibiotics, and improved nutrition via supported nursing, tube feeding or bottle feeding, maintenance of body temperature, and appropriate fluid replacement are indicated. The third generation cephalosporin antibiotic ceftiofur sodium (Naxcel; Pharmacia and Upjohn) is an appropriate choice for neonatal septicemia as it alters normal intestinal flora minimally and is usually effective against the causative organisms. Ceftiofur sodium should be administered at a dose of 2.5 mg/kg sc q 12h for no longer than 5 days. Because puppies and kittens less than 48 hours old have reduced thrombin levels, presumptive therapy with vitaminK-1 may be used (0.011.0 mg sc per neonate). Neonatal Isoerythrolysis Incompatible blood types of the parental cats have recently been implicated as a cause of feline neonatal mortality. This incompatibility arises when queens with Type B blood give birth to kittens who inherited the sires blood Type A. Type B is rare in mixed breed and Siamese cats, but is much more common in certain purebreds such as British shorthair and Devon rex cats. Type B cats have naturally-occurring antiA antibodies. When the kittens nurse and absorb these antibodies, the kittens own red blood cells are

hemolyzed, leading to anemia and organ failure. The clinical course is determined by the severity of the hemolytic reaction. In all cases, the kittens are born healthy and nurse vigorously. Some kittens may die suddenly in the first day, while others linger longer and fade during the first week of life. Clinical NI is suggested by dark red-brown urine and confirmed by documenting hemolytic anemia and the blood types of the parents. If NI is suspected, the kittens are removed from the queen and fostered on a Type A queen or bottle-fed for the first two days of life. NI can be avoided in catteries by testing the blood types of breeding animals and avoiding matings of Type B queens with Type A toms. KEY PROGNOSTIC POINTS Average reported neonatal puppy and kitten mortality rates (greatest during the first week of life) vary, ranging from 926%. OVERVIEW OF THE ISSUE Poor prepartum condition of the dam, dystocia, congenital malformations, genetic defects, injury, environmental exposure, malnutrition, parasitism and infectious disease all contribute to neonatal morbidity and mortality. KEY DRUGS, DOSAGES AND INDICATIONS Key Drug Drug Class Dose Range Ceftiofur sodium 10% dextrose Epinephrine Vitamin K1 Serum or plasma Antibiotic Glucose Catecholamine Procoagulant Blood product 2.5 mg/kg 2 to 4 ml/kg 0.2 mg/kg -1.0 mg 100150 ml/kg neonate bw

Frequency bid prn prn Once Once

Route SC IV,IO, PO IV, IC, IT SC PO, SC

Indications Bacterial sepsis Hypoglycemia Cardiac arrest Thrombin deficiency Colostral deprivation

SUMMARY Optimal veterinary intervention during the neonatal period can significantly improve neonatal survival. Evidence based techniques for neonatal resuscitation and management of immediate post partum medical conditions reduce maternal and neonatal morbidity and mortality. REFERENCES
1. 2. 3. Johnston SD, Root Kustritz MV, Olson PNS. The neonatefrom birth to weaning. In: Johnston SD, Root Kustritz MV, Olson PNS, editors. Canine and feline theriogenology, 1st edition. Philadelphia: WB Saunders; 2001. p.146167. Mosier JE. Canine pediatrics: The neonate. Proc Am Anim Hosp Assoc 1981; 48:339347. Davidson AP. Approaches to reducing neonatal mortality in dogs. In: Recent Advances in Small Animal Reproduction, Concannon P.W., England G., Verstegen J. and Linde-Forsberg C.(Eds.) International Veterinary Information Service, Ithaca NY (http://www.ivis.org/), 2003.