Neonatology and Neonatal Disorders
Management of the newborn alpaca or llama cria requires both the owner and the clinician to be familiar with the normal state to correctly identify abnormalities and to prevent or treat potential problems. Most crias in developed countries are born without complication and survive the neonatal period without incident. However, for the minority with problems, timely recognition and intervention maximize the chances of survival.
In South America, 20% to 80% of crias do not survive to weaning. Deaths occur for a variety of reasons, many of which have not been cataloged. In North American populations, the death rate is lower, but figures are not available. Well-managed farms should aim to lose fewer than 5% of their crias in a year. In general, crias suffer from the same maladies as other neonatal livestock. Dysmaturity, prematurity, dystocia, sepsis, and starvation are common problems and should be handled in the same way as in other species. In contrast, crias appear to have higher rates of certain problems such as those related to congenital malformations.
Abnormal neonates may initially show few overt signs of disease or may show signs that are vague. Given how rapidly sick neonates can deteriorate, even these small abnormalities may indicate the need for aggressive action. Abnormalities are best detected through a thorough postnatal checkup, routine, consistent monitoring of progress according to the timetable in Chapter 25, generally observing activities, including nursing, elimination, and physical activity, and charting changes in size and body weight. Even small changes such as failure to gain weight over a 24-hour period while all else appears normal could be significant, and any delay in investigating these changes and initiating treatment could result in more advanced clinical disease. Interventions may be anything from modest management changes to intensive medical care. Identifying the neonates that require interventions and determining the level are matters of experience and good diagnostic evaluation.
Crias born outside of the daylight birth window often have abnormalities and should automatically be considered to be at high risk from the start. It usually suggests either a prolonged delivery process or that a pathologic condition (sickness of the dam or fetus, abnormal placenta) triggered the birthing. Crias born following any difficult delivery likewise require greater attention. They typically take longer to achieve sternal recumbency and are slower to stand and nurse. Their suckle reflex may be depressed or absent, and they may appear depressed. Such crias require additional attention and supportive care to ensure that they acquire sufficient colostrum, oxygenate adequately, and avoid hypothermia.
Slow-starting crias may require little more than simple, but immediate, intervention. The most vital events of the first few hours of life are breathing, standing, and nursing. Breathing is the most urgent. Crias with overt dyspnea, including open-mouthed breathing or stertorous respiration, should be maintained in sternal recumbency or assisted to stand. The airway should be assessed for obstruction. The external nares should be cleared. A bulb syringe may be used to blow mucus back into the oropharynx, and a soft rubber urinary catheter may be inserted past the level of the eye in each nares for a quick assessment of choanal patency. Rubbing the thorax and dorsum also may stimulate breathing efforts. Breathing function may be assessed by arterial blood gas (ABG) analysis and thoracic radiography, and endoscopy or imaging studies may be used to assess airway patency (see Chapter 37). If hypoxemia is a concern, the cria may be placed on supplemental oxygen, and if ventilation is an issue, the cria may be intubated for mechanical ventilation. Face masks used for small animal patients may be tolerated in the short term but are hard to maintain. Nasal prongs used in human hospitals work well for crias and are self-retaining. Insufflation tubes or catheters placed in a nostril are also acceptable. When possible, supplemental oxygen should be warmed and humidified. Assessment of breathing function may be indicated even in the absence of dyspnea. Hypoxemia and hypercapnea are both important causes of neonatal obtundation, so supplemental oxygen or mechanical ventilation should be considered in any dull cria. Moribund crias are at risk of corneal ulcers because of reduced blinking reflexes. Ocular lubricants and common sense management to avoid eye trauma may be indicated.
During the period of initial assessment, after airway and breathing issues are sorted out, the cria should be examined for evidence of prematurity and external defects. Signs of prematurity are as follows: overt external defects such as facial malformations, cleft palate, limb abnormalities, a bleeding umbilicus or umbilical hernia, patent urachus, malformations of the external genitalia (Figure 42-1), and absence or atresia of the anus. Mucous membranes and sclerae should be examined for cyanosis, injection, vascularity and refill times, and the anterior chamber of the eye should be examined for hypopyon. Normal vital parameters and issues with cardiac auscultation have been discussed earlier in this text. It is important to realize that sepsis leads to hypothermia more commonly than fever. Pulmonary auscultation is the same as in other species. Some degree of “squeakiness” is normal in the immediate postpartum period, but this should resolve within an hour. Neurologic examination is difficult to interpret in the immediate postpartum period or in severely obtunded crias but may be useful in older crias.
Barring further concerns requiring more intensive management, standing efforts may be assisted. Just as good oxygenation increases mental acuity and the desire to move, ambulation assists in chest excursions and clearance of prenatal fluid from the lungs. The three best points of contact are the sternum and the two points of the hips. Placing a towel under the abdomen may increase intraabdominal pressure and restrict breathing and may even promote body wall hernias. Encouraging a newborn to stand every 10 to 20 minutes may eventually lead to it standing on its own.
Breathing and standing are usually prerequisites to nursing, but in their absence, some form of intervention to provide nutrition and immunoglobulin (Ig) is required. If the dam has colostrum, the cria should preferably be assisted to nurse or the dam milked out so that the cria can be fed via a bottle or tube. Dams may be restrained against stall walls to allow recumbent crias to nurse (personal communication, Dr. D. Mora). Colostrum or milk may be given via a tube, pan, or bottle, and intravenous (IV) nutrition or plasma transfusion may be initiated. If the dam’s colostrum is not available, camelid or ruminant colostrum may be administered for the first 12 to 24 hours. Ruminant colostrum should be from Johne’s free herds or flocks, if possible. Bovine colostrum has also been associated with immune-mediated hemolysis in rare cases.
If colostrum is not available within the first few hours after birth, administering milk or a milk replacer is likely to be beneficial in providing fluid volume, nutrition, and the impetus for gut closure. Warmed goat or cow milk or milk replacer may be used, and an initial volume equal to approximately 3.5% of body weight appears adequate. If milk is administered in the absence of colostrum, plasma transfusion should be strongly considered. Although it has not yet been studied scientifically, some think that camelid milk has metabolic effects beyond simple nutrition, so any cria fed milk or milk replacer from another species should be observed carefully for changes in attitude or activity that could reflect the onset of a hyperglycemic disorder (see Chapter 41, “Hyperosmolar Disorder”). It is also important to remember that antibody and nutrient absorption may be affected by tissue function and oxygenation; hypoxic or otherwise compromised crias may require plasma transfusion or parenteral nutrition in spite of adequate colostral or milk ingestion or administration.
If failure of passive transfer (FPT) is suspected or diagnosed after gut closure or colostrum is not available, Ig may be given in the form of camelid plasma. Llama, alpaca, and dromedary plasma appear to be interchangeable for this purpose, with the larger species often making better donors because of their size. Overall, cross-matching for a one-time transfusion is rarely necessary, and reports of transfusion complications are rare. Plasma may be administered by intraperitoneal (IP) or IV injection. One unit (300 milliliters [mL]) is often sufficient for an alpaca, whereas a large llama cria with complete FPT may require 2 units to reach the desired range.
Transfusions should be started at a slow rate and are ideally given using a filtered blood set over 30 to 40 minutes. Heart and respiratory rates should be monitored and the infusion rate decreased if either of those parameters rises more than 10%. If anaphylaxis is a concern, particularly in an animal that has previously received a transfusion, flunixin meglumine (1 milligram per kilogram [mg/kg], IV) may be give as a premedication 5 to 15 minutes before the transfusion.
Plasma may be administered by IV or IP (ventral midline or high right paralumbar) infusion. IP infusion is common as a field procedure in crias with uncomplicated FPT. Crias with other perinatal complications often have a jugular catheter for venous access, and this route is used preferentially. Rapid IP infusions (5–10 minutes) may cause abdominal discomfort, and nonsterile technique or accidental bowel perforation or laceration may result in peritonitis or intraperitoneal hemorrhage.
Typically, slow-starting or mildly dysmature crias respond quickly to these interventions. They usually learn to nurse and stand within 48 hours, and oxygen administration is rarely required beyond 72 hours and often less than 24 hours. Lack of satisfactory progress over that time usually indicates a severe congenital abnormality or an acquired disease. As such crias require aggressive treatment, it is often best to identify them from the start.
Some slow-starting crias are underdeveloped because of prematurity or dysmaturity. Because of the variability in normal pregnancy length in camelids, it may be difficult to define exactly what constitutes a “premature cria.” However, on the basis of the available data, it seems reasonable to conclude that any cria born after less than 335 days of gestation could be considered premature. Dysmaturity further describes crias born at a normal gestational age showing evidence of prematurity. These crias are as much at risk of morbidity as are premature crias. Given the uncertainty with regard to what “normal” gestational age should be, dysmaturity is often considered the more appropriate term.
Clinical signs of dysmaturity are the same as those in other species and include obtundation, low birth weight, unerupted incisors, floppy ears or ears that are bent backwards (Figure 42-2), poor or absent suckle reflex, and silky haircoats. Tendon laxity (see later in this chapter and in Chapter 58)may result in overextension of the carpal and fetlock joints, so crias may be seen walking on their fetlocks (Figure 42-3). Crias may also have a rubbery covering on the nails of the feet and a thicker epidermal membrane that persists for longer than normal. The central incisors normally erupt 2 to 3 weeks prior to birth, so unerupted incisors suggest that a cria is underdeveloped at least to this extent. Dymature crias tend to be weak and may have difficulty standing or holding their heads up to nurse because of poor muscle development. Furthermore, dysmature crias may have incomplete structural and functional maturation of vital body systems, and this leaves them susceptible to a range of potential neonatal complications. These crias are at risk for hypothermia because their thermoregulatory control is poor, and they are prone to hyperglycemia or hypoglycemia. Respiratory system immaturity may result in poor lung expansion from lack of pulmonary surfactant, and this also reduces oxygen transfer across the alveoli. Poor oxygen diffusion together with bradypnea results in hypoxia. It is unknown when surfactant is produced in the lungs of camelids, but those with unerupted incisors are especially at risk. The intestinal mucosa may also be inadequately mature in premature crias, which results in inefficient absorption of colostral antibodies. More than half the dysmature crias presenting to one referral hospital had FPT.1
Recognizing the clinical signs of dysmaturity is vital for newborn crias, as they may deteriorate rapidly. Early intervention is key to their survival. One report showed a 75% survival rate, and this was attributed to the fact that 87.5% of cases were presented within 24 hours of birth.1 Therapeutic measures may include oxygen administration, IV fluid administration, and provision of warmth. The contents and rate of administered fluids should be tailored to the specific needs and blood abnormalities; nutritional support should not be neglected. Additionally, aminophylline (2 mg/kg, subcutaneously [SQ], q4h for 24 hours, followed by q6h for the next 24 hours and q8h for the next 24 hours) may be used proactively or therapeutically when concerns about breathing exist. Lung surfactants have also seen some use.
Tendon laxity in premature crias may resolve spontaneously once the newborn cria starts weight bearing and the ligaments and tendons strengthen from use. In severe cases, splinting of the forelimbs from the elbow to below the fetlocks may be necessary. However, splints must not be placed for too long, as they may create more laxity. All crias with splints should be evaluated daily for evidence of progress or development of complications.
The slow-developing cria that does not respond to conservative management, the severely obtunded newborn that never appeared vigorous, the healthy cria that acutely developed severe clinical signs, and any cria in respiratory distress all count as “critical crias.” Crias born with low birth weight, after gestation of less than 335 days, outside of the daylight birth window, following a difficult birthing, or by cesarean section are overrepresented in this group. The critical nature of the disorder may be immediately apparent, or first recognized when conservative measures fail. Generally, the earlier the critical cria is recognized and treated, the better is the outcome.
Neonatal body systems are not as resilient as those of adult animals, and relatively minor events may have severe adverse effects. Fortunately, the same factors that promote these acute, severe presentations often allow for rapid, dramatic recoveries. Opportunistic bacterial pathogens may proliferate rapidly in the immunocompromised neonate but also respond quickly to the appropriate antimicrobials. Hypoxemia, or hypothermia all may rapidly improve with the initiation of treatment. Rapid recoveries are especially likely in crias that once were vigorous. Slow starters or those severely affected at birth are more likely to have a congenital defect, and in many cases those are irreparable.
The most common critical problems in neonatal crias less than 2 weeks of age relate to environmental conditions (hypothermia or hyperthermia), nutritional management (failure to nurse resulting in dehydration; hypoglycemia, FPT, or both; and subsequent sepsis), metabolic abnormalities related to organ dysfunction or general lack of well-being (hypoxemia, metabolic or respiratory acidosis, azotemia, hepatic lipidosis, or hyperglycemia), enteritis, and congenital morphologic impediments or organ dysfunction, including dysmaturity. Multiple mechanisms may contribute in individual cases, so a complete diagnostic evaluation is recommended. Some of this is warranted for some slow-starting crias as well before they reach the critical stage.
Components of this evaluation may include a more thorough physical examination, hematologic and biochemical blood evaluations, ABG analysis, culture of blood and potentially other abnormal body fluids, blood Ig determination, fecal investigations, and imaging studies.
Hematologic evaluation is mainly helpful for diagnosing infection or anemia. With neonatal sepsis, gram-positive organisms often evoke neutrophilia with a left shift, whereas gram-negative organisms often acutely lead to neutropenia,2,3 which resolves over 3 to 5 days. Hyperfibrinogenemia, a left-shifted leukogram, and toxic changes in leukocytes both provide supportive evidence for sepsis but also may be absent in septic crias. The stress response, with its tendency to increase blood neutrophil counts, may mask neutropenia, so it is important to look for other evidence of stress (hyperglycemia, lymphopenia) and to mentally compensate for these: A normal neutrophil count in a stressed camelid, especially one with a left shift or toxic morphology of neutrophils may still be evidence of sepsis. Mycoplasma haemolamae infection has also been identified in newborns and may be identified on blood smear or by polymerase chain reaction (PCR).4
Measuring plasma Ig concentrations also may provide indirect evidence of sepsis. Low immunoglobulin G (IgG) in a neonate may either be a predisposing factor to sepsis, often related to FPT, or reflect Ig consumption caused by infection. The longer after birth that IgG is measured, the less can be said definitively about passive transfer, especially in sick crias. Regardless, many hypogammaglobulinemic sick crias would benefit from a plasma transfusion.
Blood biochemical abnormalities of particular importance include changes in blood glucose, electrolyte abnormalities, azotemia, metabolic acidosis with or without hyperlactemia or a high anion gap, hypoproteinemia (particularly hypoalbuminemia or hypogammaglobulinemia), evidence of fat mobilization, and increased activity of liver or muscle enzymes. It is a dangerous misperception that the majority of sick neonates need supplemental glucose. Only 13% of sick crias in one unpublished study had hypoglycemia, including only 11% of crias less than 24 hours old, but 14% had blood glucose concentrations greater than 200 milligrams per deciliter (mg/dL; 11 millimoles per liter [mmol/L]). It is, therefore, imperative to measure glucose before supplementing it. The most likely causes for hyperglycemia are stress and administration of glucose or a glycogenic agent, often compounded by insufficient water intake. Camelid milk may also play a role in suppressing hyperglycemia. The most likely causes for hypoglycemia are inadequate milk intake, potentially compounded by shivering or seizures, sepsis, or liver failure. If hypoglycemia is identified, it should be addressed promptly. The seizure threshold in crias appears to be just under 40 mg/dL (2.22 mmol/L) of glucose, so supplemental glucose is recommended for anything less than 70 mg/dL (3.9 mmol/L). Rapid infusion of 0.5 mL/kg of 50% dextrose, or preferably a slow infusion of 3 to 5 mL/kg of 10% dextrose over 5 to 10 minutes may be used.
High blood glucose concentrations become clinical through diuresis and dehydration of the brain and other tissues.5 Serum sodium concentration is a good indicator of the severity of dehydration from glucose diuresis: When sodium climbs to greater than 165 milliequivalents per liter (mEq/L), aggressive measures to replace fluid volume and decrease blood glucose are indicated. Very high glucose concentrations may be combated with insulin (regular insulin, 0.2 units/kg, IV, as often as hourly) or less aggressively with subcutaneous insulin. The combination of hyperglycemia and hypernatremia is termed hyperosmolar disorder. Its pathogenesis and treatment are discussed in Chapter 41. Hypernatremia and hyperchloremia are much more common in sick crias (roughly 14%) than hyponatremia or hypochloremia (roughly 1%), so salt loading should be avoided under most conditions.
Hypokalemia (38% of sick crias) caused by anorexia is relatively common and may be addressed by IV supplementation or milk feeding. Vigorous supplementation is rarely necessary. Azotemia was found in 14% of sick crias in one unpublished study. The minority of these had renal failure or congenital abnormalities; most were in hypovolemic or septic shock and responded well to fluids. Evidence of fat mobilization was not uncommon, and hepatic lipidosis was found in 12% of nonsurviving, live-born crias, with the youngest being 2 days old. These findings highlight the need for nutritional support, and that factors beyond pregnancy-related or lactation-related negative energy balance may lead to disorders of fat metabolism in camelids. Hyperlipemia, high blood concentrations of nonesterified fatty acids (NEFAs) or β-hydroxybutyrate (BHOB) or high activities on liver enzymes all suggest such a disorder might be developing. Diagnosis and treatment of disorders of energy metabolism is covered in Chapter 41.
Acidosis is a relatively common finding in sick crias. It may be underdiagnosed in general practice because of lack of diagnostic capability. Neonates with fluid-filled lungs, severely obtunded crias, and those with pneumothorax, diaphragmatic paralysis, or hernia may have respiratory acidosis. Unless hypoventilation can be corrected by addressing the underlying condition, mechanical ventilation may be required.
Metabolic acidosis is more common. Simple bicarbonate loss is less common than in calves but is seen in some crias with diarrhea and others with apparent renal tubular acidosis. Acidosis without dehydration has also been described.6 The pathogenesis of this is not completely understood. Crias occasionally get lactic acidosis from grain overload or fermentation of milk, but hyperlactemia is more commonly the result of septic or hypovolemic shock. Ketoacidosis is also seen. Treatment of acidosis depends partially on the pathogenesis. With lactic acidosis or ketoacidosis, the primary strategies are to decrease production and increase elimination of the organic acid. Both these may often be achieved by rehydration. Ketoacidosis may also require the same treatment as that for hepatic lipidosis, and intestinal fermentative conditions may need to be treated in the same way as grain overload. If the blood pH is below 7.25, bicarbonate administration may be necessary as well. Sodium bicarbonate administration is also the cornerstone of treatment of bicarbonate-losing conditions, particularly when blood pH is less than 7.25. Multiplying the base deficit (or 24 mEq/L minus the observed bicarbonate value) by 0.5 by body weight in kilograms yields the total bicarbonate deficit. Half of this may be given within the first hour of fluids and the second half over the next 2 to 4 hours. Bicarbonate administration often temporarily corrects acidosis, but repeated monitoring is necessary to determine whether further doses should be given. Bicarbonate should also be avoided with respiratory acidosis, as hypercapnea may worsen.
Dehydrated or anorexic crias or those in shock should be treated with fluids. Although oral treatment is possible, the tubing procedure is often stressful for the neonatal cria, as its gastric capacity is only about 3.5% of whole body weight. Therefore, repetitions should be minimized. The quantity and type of fluids are often different from those for other species. Camelid babies are more prone to hypoproteinemia, hypernatremia, and hyperglycemia compared with calves or foals. They rarely are severely dehydrated but more frequently have septic shock or renal or hepatic compromise. In general, the initial bolus may be smaller (30 mL/kg), the subsequent rate may be slower (up to 100 mL/kg/day), and fluids containing glucose or lactate should be avoided without specific indication. A higher initial bolus (up to 90 mL/kg) may be given if the cria is overtly hypovolemic and has reasonably high or normal blood protein concentrations. If the cria is hypoglycemic, fluids may be spiked with glucose. If the cria is hyperglycemic and hypernatremic, mildly hypotonic fluids may be formulated by adding sterile water to isotonic saline or polyionic fluids; these fluids should be given at approximately 4 mL/kg/hour or slower and blood sodium and glucose carefully monitored.
Plasma is also a valuable adjunct, both because of failure of passive transfer and postnatal protein loss. On the basis of our laboratory equipment, we usually recommend a transfusion when total protein is less than 4 g/dL, when albumin is less than 2 g/dL, or when failure of passive transfer is confirmed or suspected. Synthetic colloids are being used in camelids with increasing frequency, but in crias, the provision of Ig is often as vital as the provision of a colloid, so plasma is usually preferable.
Plasma should be administered at 20 to 30 mL/kg. It is more effective than crystalloid fluids at expanding volume in sick neonates, since such crias often have increased endothelial permeability from inflammation. Plasma should be administered using a filtered administration set. Larger volumes (30 mL/kg) should be given over at least an hour. Faster administration may result in tachypnea, dyspnea, and evidence of central nervous system (CNS) disease. In one recent study, 30 mL/kg of camelid plasma was administered to clinically healthy alpaca crias with FPT over 90 minutes.7 This resulted in measurable plasma volume expansion, which appeared to be safe, and also a considerable improvement in arterial oxygen pressure. However, treated crias also showed a reduction in lung volume, and it was suggested that this may result in complications for those crias having preexisting cardiopulmonary compromise. Therefore, greater care would be advised in administering large-volume plasma transfusions to any cria with suspicion of cardiopulmonary issues or systemic disease. Monitoring changes in central venous pressures during a transfusion may be helpful in preventing such complications. Clinically, the observed response during a plasma transfusion may be quite rewarding.
Broad-spectrum antibiotics are usually indicated. Most injectable antibiotics used in foals or calves may be used in crias at similar dosage rates and intervals. Popular camelid regimens are covered under “Sepsis” later in this chapter. Nonsteroidal antiinflammatory drugs (NSAIDs) are similarly used. Taking into consideration fears about gastric ulceration, a reduced dose of flunixin meglumine (0.5 mg/kg, IV, q12-24h) is often used rather than the “full” dose.
By the time most crias present for evaluation, they often would benefit from IV fluids or other medications. Therefore, it is reasonable to place an IV catheter early in the evaluation (see Chapter 32) so that emergency treatment can be initiated while the examination is under way. Furthermore, blood samples can be collected from the catheter immediately after sterile placement for hematology, biochemistry, and culture, thereby reducing the number of venipuncture sites. Hematoma formation is even more common in crias than in adults, and each venipuncture increases the chance of introducing pathogenic bacteria into the bloodstream of the neonate.
If venous access is not possible because of hypovolemia, intraosseous infusion may be achieved by placement of an 18-gauge spinal needle into the proximal femur. Fluids may be administered easily by this route and blood pressure restored, so that an IV catheter may be placed.
Hypothermia may be a routine finding in underactive crias or those subjected to harsh weather conditions or may be a sign of more severe disease. As such, it may indicate the need for increased management or intensive interventions.
During pregnancy, the fetal temperature is 0.3°C to 0.5°C higher than that of the mother because of higher fetal metabolic rates. At birth, neonates are subject to a rapid drop in external temperature and need to rapidly increase heat production to keep warm. For this, they are highly dependent on nonshivering thermogenesis (NST).8 This process takes place in the mitochondria of brown adipose tissue and results in an uncoupling of fatty acid oxidation such that heat energy is produced instead of adenosine triphosphate (ATP). It is dependent on adequate oxygenation, making hypoxemic neonates more susceptible to the development of hypothermia. Additionally, premature neonates are likely to have inadequate reserves of brown adipose tissue, which develop late in gestation under the influence of NST inhibitors. Shivering generates additional heat, but the impact of this is small in neonates because of their small size and immature musculature. The presence of brown adipose tissue has not been specifically documented in camelids to date, so the extent of the role of NST in averting hypothermia in crias is uncertain. Thyroid hormones may also play a role in enhancing thermogenesis in the newborn. Neonatal llama crias have been shown to have very high blood thyroxine concentrations at birth, which decrease gradually over the first 90 days of life.9
Crias born in cooler environmental temperatures, particularly in winter, are especially susceptible to hypothermia because of the greater temperature differential and the potential for increased heat losses from evaporation from a wet neonate. The epidermal membrane helps prevent some of this evaporative cooling but disintegrates soon after birth. Therefore, if females are expected to give birth during cooler periods of the year, they should be watched particularly closely or brought indoors so that parturition occurs in a warmer location. Ideally, matings in cold climates should be scheduled so that the birthing season occurs during the spring or summer months to minimize this problem.
Hypothermic neonates are depressed and lethargic and have reduced reflexes and poor ventilation. This, together with poor cardiac function, results in hypoxia, acidemia, and cardiac dysrhythmias.10 Hypothermic neonates are susceptible to FPT because of decreased nursing activity and possibly gut function. Hypoglycemia, although uncommon, may develop concurrently as hypothermic neonates deplete their energy reserves. Additionally, prolonged hypothermia may result in damage to the intestinal epithelium because of hypoxia, predisposing the neonate to clostridial overgrowth and pathogen invasion.11
Crias with hypothermia should be warmed. This involves placing them in a warmer environment away from drafts, drying them off if they are wet, and using external heat sources such as heat lamps, warmed towels and blankets, and hot water bottles. Forced-air warming blankets are particularly effective in crias because of the relatively larger surface area. If heating pads or lamps are used, appropriate insulation from direct heat should be used, and care must be taken to ensure that a recumbent cria is turned frequently to avoid overheating. Excessive heat may result in cutaneous vasodilation, which may be detrimental to the cria by reducing core temperature and resulting in further cardiovascular compromise. This is also true of warm water bathing, which is therefore not recommended. Caution must be exercised if heat lamps are used because some bulbs may pose a fire hazard. Bulbs should be positioned above the height of any potential kicks from the dam. Crias that have become hypoxemic as a result of hypothermia, and vice-versa, benefit from oxygen administration.
The rectal temperature for normal crias is 37.8°C to 38.9°C (100°F–102°F).12,13 Therefore, hyperthermia in a neonate would be defined by a rectal temperature of 39°C (102.2°F) or greater. The most common cause for hyperthermia is fever related to infection. However, it is an inconsistent finding under those circumstances and should not be considered a prerequisite for a diagnosis of sepsis in camelids of any age. None of 21 crias with sepsis had a rectal temperature greater than 39°C (102.1°F) in one study, regardless of whether gram-positive or gram-negative bacteria were cultured from blood or tissue samples.2 In fact, 7 (33%) were actually hypothermic. In another retrospective study, only 2 of 6 crias with gram-negative sepsis were pyrexic.3 This compares well with findings in septicemic foals, in which only 30% of cases were pyrexic.13
The differential diagnoses for a high body temperature in neonatal llamas and alpacas include bacterial or viral infections, high environmental temperature, muscle tremors, or seizure activity. Bacterial infections are a likely sequel to failure of passive transfer. Muscle tremors may result from cerebral edema or ingestion of tremorgens. Seizures may result from a variety of CNS disorders (Box 42-1). In certain areas of the world, environmental temperatures may become extremely high and, especially when compounded with high humidity, may lead to hyperthermia. Neonates are particularly vulnerable if they are unable to seek suitable refuge, Furthermore, neonates that are suffering from underlying bacterial or viral infections are less able to thermoregulate and more susceptible to hyperthermia if unable to move to shade. High ambient temperatures may be focal as well, as in a stall with a heat lamp.
Fever is brought about by the production of pyrogenic cytokines, especially interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α, in response to a variety of conditions including infections, inflammation, trauma, or immunologic conditions.10 The production of these cytokines results in a cascade of effects, including the production of acute-phase proteins and stimulation of the immune response while also resulting in behavioral changes such as increased sleep, reduced appetite, and separation from others that may allow recovery and reduced spread of infectious agents.
Hyperthermic neonates often develop tachypnea to increase evaporative heat loss. Heat loss from the body surface, aided by peripheral vasodilation, is limited to the small areas in the axillary and inguinal areas, where less hair coverage is present. When lying in closed sternal recumbency, heat loss from these areas is minimized because of lack of conductive loss from circulating air. Affected individuals are lethargic. At rectal temperatures higher than 41.5°C (106.7°F), the body’s normal thermoregulation fails, peripheral vasoconstriction occurs, and cardiac output falls with reduction in blood pressure.10 Organ failure, coagulopathy, and myocardial necrosis may develop subsequently. Seizures may occur at these temperatures because of alterations in the function of temperature-sensitive ion channels and also the production of the pyrogenic cytokine IL-1β that has been shown to enhance neuronal excitability.14 Relatively small increases in brain temperature predispose the brain to hypoxic injury.8
If hyperthermia is identified in a neonate, it is likely to be significant, and therefore the clinician should attempt to identify the underlying cause and provide the appropriate treatment. It is particularly important to rule out or identify bacterial infection, since mortality rates may be high if this is not treated early and aggressively (see “Sepsis” below). Neonates that are suffering from heat stress as a result of environmental conditions should be cooled. This may be achieved by removing the cria from the heat source, making use of fans, clipping of fleece, and using ice packs. Ice packs may be particularly effective if placed in the inguinal area close to the femoral arteries and veins; care should be taken, however, to wrap the ice packs in towels and not to place them directly onto the skin, as this may cause cold burns. NSAIDs are also indicated for neonates suffering from heat stress or seizures caused by hyperthermia. The use of NSAIDs for reducing fever from other causes is controversial because of the beneficial effects that fever may have, including stimulation of the immune response, as well as the potential harmful GI and renal effects of NSAIDs. They should therefore be used with care.
Sepsis is defined as systemic inflammatory response syndrome (SIRS) with either documented or suspected infection by bacterial, viral, fungal or rickettsial agents.2 In crias, gram-negative and gram-positive bacterial sepsis appear to be the most common causes.2,3,12,15 E. coli, Pseudomonas, β-hemolytic Streptococcus, Enterococcus spp., Listeria monocytogenes, and Citrobacter are the most common isolates, with gram-negative organisms making up 54% of diagnoses in one study and 72% in another review.2,16 Most organisms are considered opportunists and infect individual crias, as opposed to causing outbreaks of disease. Neonatal sepsis is a common sequel to FPT and hence is common in crias after difficult births and in those with agalatic dams or with other risk factors contributing to FPT. It may also occur in crias shown previously to have acceptable passive transfer.
Sepsis is characterized by weakness, lethargy, pyrexia or, more commonly, hypothermia, tachycardia, tachypnea, and failure to nurse or gain weight.2,3 Evidence of dehydration, injected mucous membranes, or organ-specific signs, including diarrhea, colic, abdominal distention, hypopyon, seizures, blindness, ataxia, dyspnea, dysuria, lameness, or swollen joints, may exist. Signs may spread from one body system to another and may occur peracutely or gradually. When sepsis occurs before or soon after birth, it may be difficult to differentiate from dysmaturity, birthing complications, or disorders caused by birth defects, all of which may lead to severe obtundation or organ-specific signs. The greater the separation from the birth event, especially in crias that have shown days to months of normalcy, the more likely it is that local or systemic infection is the root of the problem. Generally, sepsis should be considered a possible cause or complication of almost any disease or disease sign in a neonate.
Initial physical examination findings are often relatively unremarkable, emphasizing the need for laboratory and possibly imaging evaluation of many sick neonates. Hematologic abnormalities often include leukocytosis or leukopenia, both often accompanied by a left shift and toxic changes in leukocytes. Neutropenia appears to be more common with gram-negative infections, whereas gram-positive infections are more commonly associated with neutrophilia, unless the infections are overwhelming.2 Blood work may also reveal findings suggestive of FPT, including hypoproteinemia and hypoglobulinemia. Specific tests of blood Ig concentrations provide more specific evidence. Measurement of total blood protein is not a particularly good predictor of FPT in septic crias but still provides useful information on whether a sick cria is hypoproteinemic or not.2 Additional blood abnormalities that may develop with sepsis include hypoglycemia or hyperglycemia, metabolic acidosis as a result of shock with or without diarrhea, azotemia as a result of dehydration, nephritis or kidney failure, hypoxemia or respiratory acidosis as a result of pulmonary infection or weakness-associated hypoventilation, electrolyte abnormalities, and increases in bilirubin and liver enzymes. Analysis of other body fluids, including peritoneal, pleural, joint, or cerebrospinal fluid (CSF), may also reveal local evidence of infection, if that part of the body is involved.
Imaging studies are not necessarily part of a routine evaluation but may provide useful information if a particular part of the body deserves further investigation. Conventional radiography is most useful for assessing the chest when abnormal lung tissue, masses, or fluid accumulation is suspected, or for identifying lytic bone. Ultrasonography is useful for identifying the nature and amount of fluid buildup in body cavities and for identifying tissue masses. Cross-sectional imaging studies may be used to assess any tissue but are currently used most to assess the CNS and other areas poorly imaged by other techniques.
A presumptive diagnosis of sepsis may be made by identifying compatible clinical signs and diagnostic test abnormalities, in some cases supported by historical evidence of increased risk such as a difficult birth or other factors associated with FPT. Confirmation requires seeing the organism on cytologic examination or growing it on bacteriologic culture. Cultures are usually performed on blood, but other suspect body fluids or possibly tissue samples collected postmortem may be used. Because of the rapidity with which neonatal sepsis can progress, aggressive treatment is usually warranted based on initial clinical suspicion. In many cases, simply recognizing that a cria is at risk for developing sepsis justifies treatment. Treatment follows the guidelines for critical crias, including fluid, environmental, and nutritional support, appropriate use of plasma to maintain oncotic pressure and provide Ig, antiinflammatory medications, and most importantly, antibiotics. Greater risk of capillary leakiness or body loss of protein exists in any animal with sepsis, so blood protein concentrations should be monitored and the animal frequently observed for clinical evidence of edema, particularly when on IV fluids.
A broad-spectrum antimicrobial regimen is usually appropriate, with particular consideration for gram-negative coverage. Combination therapy of a β-lactam agent (crystalline penicillin: 22,000 units/kg. IV, q6h; or ceftiofur: 8 mg/kg, SQ, intramuscularly [IM], or IV, q12h) with an aminoglycoside such as gentamicin (5 mg/kg, IV, q24h for 5 days)17 or amikacin (15 to 18 mg/kg, q24h for 5 days) has seen widespread usage and resulted in many clinical cures. Other agents or combinations have not been as extensively used but may be supported by specific culture results. Antibiotics may have to be continued longer than suggested above, if sepsis persists. When using an aminoglycoside, monitoring of blood creatinine concentrations, preferably at least every 48 hours during treatment, may allow timely recognition of renal damage before it is irreversible.
Further management of septic crias involves regulation of body temperature, provision of oxygen in critical cases, provision of nutrition, and monitoring of hydration status and hematologic responses. Crias must be monitored for development of hypopyon, uveitis, conjunctivitis, or neurologic signs. If hypopyon is observed, administration of mydriatics such as atropine drops may minimize the risk of synechiae formation, which may subsequently result in glaucoma and necessitate enucleation. Prognosis of crias with sepsis is generally fair, if the condition is recognized and treated early and no preexisting morphologic defects such as dysmature lung or inadequate pharyngeal reflexes that promote continual compromise are present. Vertebral body or tissue abscesses may result in long-term or future complications.
Any evidence of insufficient respiratory function is usually considered the most urgent problem in a critical patient because of the potential for inadequate tissue oxygenation. Respiratory function may be affected by a variety of factors, including respiratory tract or cardiovascular anatomy; the presence of abnormal fluids, tissues, or infection affecting areas of air movement or gas exchange; mental or physical impairment of ventilation; abnormal blood flow patterns through the lung; and other factors. Some of these factors are more likely to be identified during the neonatal period than in older animals, particularly those relating to anatomic defects or infection. Assessment of the airway and respiratory function requires a thorough physical examination, imaging studies of the upper airway or chest, and ABG analysis.
Abnormalities in respiratory function may lead to obvious or subtle signs. Obvious signs include tachypnea, dyspnea, flaring of the nostrils, open-mouth breathing, and loud sounds coincident with breathing efforts. More subtle signs include some degree of obtundation, poor growth, cyanosis, and a lower level of activity than expected.
Dyspnea, tachypnea, and open-mouth breathing are common in neonatal camelids with either an upper airway obstruction or fluid in their lungs but may be transiently present in healthy crias as well (Figure 42-4). They should resolve within an hour in healthy crias. If pathologic, these problems are usually the most urgent and demand immediate attention. Simple obstructions have been described earlier in this chapter, and anatomic airway defects are covered in Chapter 37. Trying to pass a feeding tube or rubber catheter may quickly yield information about airway patency and may remove mucus. Imaging studies are necessary for more thorough assessment. Respiratory obstructions should be removed or bypassed, if possible. This may require surgical intervention.
Figure 42-4 Open-mouth breathing. This may last a few hours in normal newborns, or may be a sign of congenital airway malformation or lower respiratory tract disease. Note also the curled ears characteristic of prematurirty or dysmaturity.
Lower airway disease may be caused by pulmonary dysmaturity, atelectasis following prolonged recumbency, inadequate ventilation to remove fetal fluids, meconium or milk aspiration, fluid overloading, left-sided heart failure, or infection. Dysmaturity may be inferred from an early delivery date but is usually diagnosed by demonstrating hypoxemia and radiographic evidence of diffuse alveolar pathology in crias without other evidence of pneumonia, aspiration, or pulmonary edema. Inadequate ventilation may be readily apparent in severely obtunded crias in lateral recumbency with poor chest excursions; in more vigorous crias, demonstration of respiratory acidosis, pneumothorax, poor coordination between the diaphragm and intercostal muscles, or inadequate chest movement may be necessary. Meconium aspiration may be inferred in a meconium-stained cria after a difficult birth, and milk aspiration is often the product of bottle-feeding the less vigorous neonate. Fluid overloading may be inferred from the treatment history, with further confirmation coming from the identification of hypoalbuminemia or hypoproteinemia on blood work. Infection is covered under “Sepsis” above.
More than one upper and lower airway problem may be present simultaneously. Factors which induce dyspnea facilitate feed aspiration, and anything that impairs early drinking promotes failure of passive transfer and secondary sepsis. Although one factor may be causative of the others, all may require specific treatments at the time of presentation.
South American camelids are known to have some unique adaptations that allow them to thrive in low oxygen environments such as those found at high altitude. Their oxyhemoglobin dissociation curve is shifted to the left of those of humans and many other mammals, so camelid hemoglobin (Hb) has increased affinity for oxygen in the lungs, allowing high oxygen saturation of Hb (≥90%) even at high altitude and low inspired oxygen concentrations.18–20 However, the oxygen is released just as easily in the tissues, reflecting good oxygen extraction to meet the demands of tissue hypoxia. Fetal llamas have been shown to have even more efficient tissue oxygen extraction.21 Llamas and alpacas have been shown to exhibit a much reduced pulmonary vasoconstrictive response to hypoxia such that they are resistant to the development of pulmonary hypertension at altitude.22 Furthermore, the fetal llama, in contrast to lowland species, has been shown to respond to acute hypoxia with intense peripheral vasoconstriction and only a modest increase in cerebral blood flow with reduced oxygen consumption, indicating hypometabolism, even in the brain.23 Presumably, the large decrease in peripheral oxygen consumption preserves available supplies for the brain. The fetal llama heart also receives an increase in blood flow in response to hypoxia. These fetal responses appear to be preserved into the neonatal period.24 Therefore, the physiologic adaptations of these species may explain why neonates are better able to survive hypoxia in association with congenital heart defects compared with other domestic species.
Ventilation and oxygenation are best assessed via ABG analysis. If this is unavailable, or during the gap between presentation and confirmation of abnormalities, supplemental oxygen may be administered on the basis of suspicion of hypoxemia. If the patient is breathing poorly or has hypercapnea, mechanical or assisted ventilation may be required, if other treatments do not improve the respiratory effort. Generally, supplemental oxygen is recommended whenever partial pressure of oxygen (PaO2) falls below 60 mm Hg and ventilation is recommended whenever partial pressure of carbon dioxide (PaCO2) exceeds 60 mm Hg. Supplemental oxygen may be administered using oxygen tents or cages or more commonly via nasal catheter. It is usually sufficient to administer 2 to 4 liters per hour (L/hr) of 100% oxygen. This is effective or partially effective at combating hypoxemia caused by diffusion barriers and ventilation–perfusion mismatches but is not effective when blood is bypassing the lung because of a right-to-left shunt. Efficacy may be checked by comparing ABG values on and off the supplemental oxygen; a good response suggests a more favorable prognosis. The flow rate may be decreased and oxygen finally discontinued when clinical response warrants it.
Mechanical ventilation is indicated for hypoventilating crias. Hypoventilation may be caused by pneumothorax or other causes of compressed lungs, damage to the diaphragm or thoracic wall, diaphragmatic paralysis, drug-induced respiratory suppression (e.g., following anesthesia of the neonate or dam for the purposes of dystocia resolution), head trauma–induced respiratory depression, congenital or acquired airway obstruction, or neuromuscular weakness. A tidal volume of 4 to 8 mL/kg, at the rate of 20 to 30 breaths per minute (breaths/min), and peak inspiratory pressure less than 20 centimeters of water (cmH2O) is usually adequate. Ventilation requires intubation with a cuffed endotracheal tube passed through the mouth or nasal passages or a cuffed tracheostomy tube.
Cyanosis is an additional sign of poor respiratory function. This bluish discoloration of the mucous membranes and the extremities is caused by accumulations of blood deoxyhemoglobin that exceed 2.5 grams per deciliter (g/dL). In addition to pulmonary and airway problems, cardiac defects causing blood to bypass the lungs are important contributors to cyanosis. These may include ventricular septal defect in combination with a right-sided obstructive lesion that results in right-to-left shunting, right-sided defects such as pulmonic stenosis with a patent foramen ovale, tetralogy of Fallot, transposition of the great vessels, or tricuspid atresia. These are covered in detail in Chapter 36.