2009: Treatment strategies in the perinatal mare and foal Treatment strategies in the perinatal mare and foal 1 P.R. Morresey 2 Rood and Riddle Equine Hospital, PO Box 12070, Lexington, KY, USA 3 Abstract 4 A large number of conditions are recognized in the peripartum period that have 5 the potential to impact the health and future performance of both the mare and the foal. 6 Peripartum hemorrhage can be insidious in onset and result in profound abdominal pain, 7 hypovolemia and in severe cases death of the mare. Those mares that survive the initial 8 hemorrhage may succumb some time after the apparent stabilization of the hematoma. 9 Treatment is aimed at promoting hemostasis and improving cardiovascular performance 10 while not promoting further hemorrhage. Many drugs in common use have been chosen 11 due to anecdotal reports of success or extrapolation from studies on horses or other 12 species. Large, multi-center controlled trials of therapeutic agents are lacking, this being 13 expected given the critical nature of the condition. The compromised neonatal foal is a 14 challenge to the attending clinician, who must balance the immediate medical needs of 15 the foal with the financial requirements of the client. Following the initial assessment, 16 resuscitation of the neonate must be performed in a timely and efficacious fashion. The 17 attending clinician should establish a coherent and consistent approach to cardiovascular 18 resuscitation of the foal. Following this event, stabilization of the neonate and 19 preparation for transport to a referral center if required can occur. A thorough knowledge 20 of the expected neonatal development of the foal will aid in selection of foals requiring 21 specialist intervention. 22 23 451 Keywords: Mare, peripartum, hemorrhage, foal, neonatal, resuscitation 24 Introduction 25 The peripartum period for both the mare and the foal can be a period of great risk 26 to life and future potential. A myriad of problems exist, and it is beyond the scope of this 27 presentation to cover them all. Therefore a selected few will be covered in detail: 28 peripartum hemorrhage in the mare, neonatal foal resuscitation, stabilization and 29 preparation for referral. 30 Mare 31 Considerations in the periparturient mare 32 The periparturient mare does not differ substantially from the non-pregnant mare 33 with respect to general husbandry. Routine exercise, a balanced diet and regular 34 preventative health care (teeth, deworming and vaccination) should all continue as 35 before. 36 Differences become important when they involve the overall health of the mare 37 and the effects on placental function that systemic illness can have. The goals of therapy 38 should address resolution of the precipitating problem, systemic support for the mare 39 (and therefore fetoplacental unit) and the avoidance of fetal hypoxia. 40 The overall health of the mare will be affected by any disease process resulting in 41 inappetance, fever or proinflammatory mediator production with systemic release. 42 Nutritional insult resulting in weight loss during mid-gestation has detrimental effects on 43 placental development which results in reduced fetal growth.1 Endocrine function of the 44 foal is also affected.2 45 452 Colic is also of greater concern in the periparturient mare, as this condition 46 presents a serious diagnostic challenge to the practitioner through limitations imposed 47 upon examination by the presence of the gravid uterus. Accurate differentiation between 48 gastrointestinal conditions and gestational accidents is essential but difficult in many 49 cases. Early gastrointestinal problems can appear similar to initial stages of labor. 50 Peripartum gastrointestinal conditions include large colon volvulus or displacement, cecal 51 rupture, small intestinal volvulus, enterocolitis and direct trauma to the intestine.3 52 Trauma to the gut may result in ischemic necrosis of the affected areas.4-6. 53 Compromise to the gastrointestinal tract results in the onset of endotoxemia with 54 profound circulatory dysfunction and proinflammatory stimuli occurring. Serious 55 metabolic insults can affect both the mare and concurrently the fetus. Treatment of the 56 gastrointestinal disease may involve general anesthesia with abdominal exploration 57 further insulting the fetoplacental unit. 58 Hypoglycemia of the mare resulting from inappetance or fasting while colic 59 treatment continues decreases glucose delivery to the fetus. Administration of glucose to 60 late-term pregnant mares is recommended to avoid this, as is supplementation of feed 61 material by nasogastric intubation where practical. Oxygen therapy is also recommended 62 where placental function is suspected to be compromised.7 63 Reproductive problems in the peripartum period with apparent colic as a 64 presenting clinical sign include uterine torsion, uterine rupture, uterine laceration, uterine 65 bruising and hemorrhage of the blood vessels supplying the reproductive tract.3 66 Peripartum hemorrhage 67 453 Rupture of and subsequent hemorrhage from the uterine artery is the most 68 common cause of death in mares post partum.3 The external iliac artery, utero-ovarian 69 artery, and uterine artery have also been implicated.8 In a review of central Kentucky 70 mares, reproductive complications accounted for the majority (57 of 98 cases, 58%) of 71 deaths in peripartum mares.9 Of those that died of reproductive complications, rupture of 72 a uterine artery was determined to be the cause of death in 40 cases (70%). The 73 incidence of peripartum hemorrhage in the mare has not been determined by retrospective 74 studies of large numbers of mares, instead reports of clinical cases are found in the 75 literature. Hemoperitoneum itself is a significant cause of abdominal discomfort in the 76 horse, with approximately 13% of all cases due to rupture of uterine vessels.10 77 Although usually considered a problem of the post partum period, a number of 78 reports exist of cases in the prepartum period.8,11 Peripartum hemorrhage has been 79 reported to occur at any age, however older mares are considered to be at greater risk.12 80 Age-related degeneration of arterial vessels associated with the reproductive tract is 81 suspected to be the reason for the increased incidence in older mares, coupled with the 82 increased mechanical stresses imposed by the gravid uterus. Uterine contractions and 83 obstetrical manipulations further increase stress on the vessel wall.13 Copper deficiency 84 was identified as a contributing factor in mares experiencing fatal hemorrhage, whereas 85 non-fatal hemorrhage mares had comparable copper levels to their non-affected cohorts.14 86 Peripartum hemorrhage can occur in any of the following forms: hemorrhage into 87 the peritoneal cavity, hemorrhage retained either within the broad ligament of the uterus 88 or within the uterine wall (mural hemorrhage) or hemorrhage into the uterine lumen. 89 Combinations of these may occur, necessitating thorough evaluation of mares affected by 90 454 seemingly less serious forms of hemorrhage so as to avoid non detection of life-91 threatening episodes. 92 Hemorrhage into the peritoneal cavity can lead to profound hypovolemia, pain 93 and result in peracute death. If confined to the broad ligament or uterine wall, pain can 94 still be significant but prognosis for life is better. These hematomas may be incidental 95 findings during routine reproductive examinations, or may become acutely apparent some 96 time after foaling following the onset of abdominal hemorrhage. Hemorrhage within the 97 uterine lumen is usually of less significance due to the relatively small amount of blood 98 lost from the circulating pool in most cases. 99 Diagnosis 100 Clinical parameters of horses experiencing acute blood loss and hemoperitoneum 101 have been reviewed.10,15 Consistent signs included depression, tachypnea, tachycardia, 102 poor pulse quality, pale mucous membranes, prolonged capillary refill time, cool 103 extremities and abdominal discomfort. Signs occurring less often included abdominal 104 distention, sweating, ataxia, and a mass in the broad ligament palpated per rectum. 105 Clinical pathology findings include anemia, neutrophilia, lymphopenia, 106 thrombocytopenia, hypoproteinemia, hypocalcemia, and azotemia. Measurements of 107 hemostasis (prothrombin time, parital thormoboplastin time, template bleeding time) are 108 usually normal. 109 The diagnosis of hemoperitoneum is confirmed by transabdominal 110 ultrasonography and abdominocentesis. Lesions at necropsy may include a ruptured 111 miduterine artery or ruptured broad ligament hematoma. On occasion, the source of 112 hemorrhage may be the iliac vessels. 113 455 Rectal examination is controversial, with the need to make a diagnosis balanced 114 by the concern of worsening hemorrhage. There is no evidence that rectal examination of 115 mares suffering prepartum hemorrhage adversely affects outcome.12 Rectal examination 116 may not aid diagnosis, as the hemorrhage may dissect between tissue planes and not form 117 a discrete, palpable mass in the broad ligament. Careful transrectal ultrasonography may 118 greatly aid diagnosis due to the ability to detect non-palpable lesions. 119 Treatment 120 Due to the sporadic nature of the condition, treatment modalities are derived by 121 extrapolation from studies on humans, laboratory species and anesthesia studies in the 122 horse. A number of treatments have been recommended, with both scientific and 123 anecdotal backing for those in common usage: 124 ε-aminocaproic acid. The effects of ε (epsilon) aminocaproic acid (EACA) on 125 coagulation and fibrinolysis in healthy horses have been reviewed.16,17. Partial 126 thromoplasin time (PTT) was found to be significantly decreased and α2-antiplasmin 127 activity was significantly higher. Fibrinogen was significantly lower than baseline. 128 Bolus dosage is more practical in field situations; however a recent review17 established 129 an efficacious constant rate infusion protocol. 130 The procoagulant EACA is a synthetic anti-fibrinolytic amino acid. Similar 131 agents are widely used in human medicine to arrest hemorrhage. The lysine binding sites 132 of plasminogen become saturated with EACA which displaces plasminogen from the 133 fibrin surface stabilizing the hemostatic plug.18 134 Naloxone. Naloxone is anecdotally reported and widely used in the treatment of 135 postpartum mare hemorrhage.3 Experimental evidence shows that endorphins released 136 456 by stress act on opiate receptors to depress cardiovascular function during hemorrhagic 137 shock.19 Naloxone acts as a μ-opioid receptor competitive antagonist and also has 138 (lesser) antagonist action at the κ- and δ-opioid receptors. The hemodynamic effects of 139 blood loss were shown to be ameliorated by intravenous administration of naloxone as 140 evidenced by an increase in arterial pressure, left ventricular function and cardiac 141 output.20,21 Regional blood flow differences were noted in the dog, with naloxone 142 improving circulation to the myocardium, intestine, liver and adrenal.22 In the horse, 143 naloxone (0.20 mg/kg iv) immediately following acute hemorrhage was found to counter 144 the increase seen in heart rate.23 However, this would result in a considerably higher 145 dose than that commonly in usage (8 mg) for the hemorrhaging mare. At available 146 concentrations (0.4 mg/ml) a volume of 250ml would have to be infused to achieve the 147 higher dose rate shown to be effective in acute hemorrhage situations. 148 Dexamethasone or other corticosteroids. The beneficial effects of 149 dexamethasone administration during hemorrhagic shock has been shown in dogs.24,25. 150 Increased mean arterial pressure was noted, as was improved blood flow to the 151 pulmonary, gastrointestinal and renal circulations. Furthermore, less cell damage was 152 evident as shown by decreased plasma enzyme elevations referable to damaged tissues. 153 Formalin. Formalin activation of platelet function during fixation in vitro has 154 been reported.26 The procoagulant properties of formalin (aqueous formaldehyde) in the 155 horse have been critically reviewed.27 In spite of a reported decrease in clotting and 156 bleeding time in goats,28 administration was shown to have no effect on primary or 157 secondary hemostasis in normal or aspirin-treated horses.27 Behavioral effects, 158 tachycardia, lacrimation, salivation and muscle fasciculations were seen at higher doses. 159 457 Despite no effect on coagulation seen in that study, the usage of intravenous formalin for 160 its purported hemostatic properties is widely practiced in equine medicine. 161 Yunnan baiyao. Yunnan Baiyao (or Yunnan Paiyao, literally white medicine 162 from Yunnan) is a hemostatic powder of largely unknown constituents. Purported uses 163 include hemostasis, relief of pain, diminishment of swellings and the improvement of 164 circulation to the tissues. The mechanism of action is unknown. Experimentally, 165 template bleeding time of halothane anesthetized ponies was decreased when compared 166 to baseline values following the administration of yunnan baiyao 4 h prior to and 167 immediately preceding induction of anesthesia.29 Activated clotting time was not 168 affected in this study. Anecdotal reports indicate widespread usage by equine 169 practitioners with reported favorable results. 170 Acepromazine. The pharmacokinetics and pharmacodynamics of intravenous 171 acepromazine have been extensively reviewed in the horse.30,31 Use in the hemorrhaging 172 mare is controversial as concerns are held for the potential exacerbation of hypovolemia. 173 However, use allows the hypotensive restoration of adequate circulatory blood volume 174 with a diminished chance of dislodging the hemostatic plug. 175 Butorphanol. Butorphanol tartrate is widely used for control of pain and 176 chemical restraint in the hemorrhaging mare. Concurrent judicious use of the α2 177 adrenergic agonists (xylazine, detomidine) further aids in control of anxiety. 178 Butorphanol is a partial agonist/antagonist at the μ opioid receptor and an agonist at the κ 179 opioid receptor. Therefore, potential for antagonism exists with the concurrent usage of 180 butorphanol and naloxone. 181 458 Blood transfusion. Whole blood is the fluid of choice in cases of hemorrhagic 182 shock. However, this is often not available; therefore isotonic polyionic solutions are 183 administered to maintain circulating volume, with consideration of their relatively short 184 time within the vascular space. When blood is lost from the intravascular compartment, 185 central venous pressure decreases and blood lactate concentration increases significantly 186 when compared with baseline values in the healthy horse.32,33 Surprisingly, heart rate 187 and venous blood gas analysis do not change significantly in the initial period. 188 Therefore, blood lactate concentration is a useful measure of hypovolemia in horses in 189 situations of acute loss before other parameters become abnormal. Also, it may be useful 190 to indicate the need for blood transfusion and monitor responses of horses when whole 191 blood is administered.32 192 Plasma. The administration of plasma is widely practiced for the provision of 193 clotting factors and oncotic support to the hemorrhaging mare. This is useful in 194 situations where anemia is severe once the mare is stabilized and whole blood is not 195 available. In an emergency situation, this is less practical as plasma needs to be 196 administered slowly and the benefit of administration will not be realized in a clinically 197 relevant time frame. Volumes in common usage (1 L) are unlikely to measurably affect 198 oncotic pressure and hemodynamic performance. 199 Hypertonic saline. In situations of acute blood loss, the restorative fluid used is 200 of lesser importance as long as an appropriate volume is given.34 In human medicine, 201 considerable interest has been shown in the use of hypertonic saline dextran (HSD) in 202 situations where significant hemorrhage has occurred.35 Controversy still surrounds the 203 use of hypertonic solutions for rapid restoration of intravascular volume.36 In the 204 459 hemorrhaging mare, use of hypertonic saline is widely practice but similarly controversial 205 due to the possibility of rapid plasma volume expansion causing a deleterious rapid spike 206 in blood pressure. 207 Hetastarch. Hetastarch, 6% hydroxyethyl starch solution, is an artificial colloid 208 used as a plasma volume expander. It has oncotic activity only and is not a blood or 209 plasma substitute. Hetastarch is elimintated over a prolonged period by the kidneys. In 210 situations where rapid plasma volume expansion is needed, hetastarch can be given as a 211 series of rapid bolus doses in contrast to plasma which must be slowly administered. For 212 this reason it offers an attractive way to rapidly ameliorate the effects of acute blood loss. 213 However, one retrospective study suggests that intraoperative use of hetastarch in human 214 cardiac surgery may increase bleeding and subsequent blood transfusion requirements.37 215 Polyionic replacement fluids. Volume restoration by polyionic fluids is widely 216 practiced in the hemorrhaging mare. These fluids rapidly leave the vascular space (30 217 minutes) and do not provide a long term solution to hypovolemia, but instead provide a 218 rapid transient means to combat blood loss. When used in conjunction with colloids 219 (plasma and hetastarch) or hypertonic saline a more prolonged effect can be expected. 220 Care must be taken to avoid overzealous plasma volume expansion to preserve the 221 hemostatic plug. 222 Lidocaine infusion. The historical use of lidocaine as a systemically 223 administered analgesic for intractable human pain has been reported.38 Analgesic effects 224 in horses have only been relatively recently reported.39 When practical, a constant rate 225 infusion of lidocaine is an excellent analgesic for the hemorrhaging mare, especially if 226 hemoperitoneum is present. An appropriate dosage regimen is an initial lidocaine 227 460 loading dose (1.3 mg/kg iv) as a slow bolus, followed by a constant rate infusion (0.05 228 mg/kg/min iv), preferably using a fluid pump however this is not essential. 229 Management 230 Although controversy exists as to the utility of various therapeutic agents, 231 ensuring the mare is as calm as possible and not exposed to undue stress is widely agreed 232 upon. Care should be taken during restraint to not excessively stress the mare by using a 233 combination of physical and chemical restraint. 234 Broad spectrum antimicrobial therapy is indicated to prevent the establishment of 235 bacterial overgrowth in any hematomas or stagnant pools of blood post hemorrhage. 236 Anti-inflammatory therapy should be maintained following the initial insult to minimize 237 pain and distress, which may lead to increased blood pressure and restarting of 238 hemorrhage. 239 Fluid therapy should be approached with caution and closely monitored. Rapid 240 plasma volume expansion can lead to hemodilution, loss of the hemostatic plug and 241 restarting of hemorrhage. This must be weighed against the necessity of restoration of an 242 adequate circulating volume in the hypovolemic mare. The mare will succumb to 243 hypovolemia not anemia in the acute phase of blood loss.34 The signs of hemorrhage and 244 hypovolemia are well known: visible distress or colic signs, muscle fasciculations, 245 sweating along the flanks, flehmen, elevated heart and respiratory rates, and palor of the 246 mucous membranes. Should these signs return during fluid restoration, an immediate 247 decrease in the rate of admission should be considered. In the healthy horse, where 248 potential for hemorrhage is not present, one-half of the calculated fluid deficit can be 249 administered rapidly, with the remainder of the deficit given over the ensuing 24 h. 250 461 However, in the mare affected by peripartum hemorrhage, this initial rapid high volume 251 administration is not possible. 252 A representative treatment plan for the author follows. Subsequent to the 253 diagnosis of hemorrhage, an intravenous catheter is placed and an initial 5 L bolus of 254 polyionic fluids containing 20 g ε-aminocaproic acid as a hemostatic agent is given over 255 30 min. Concurrent with this, acepromazine is administered intramuscularly to allow 256 hypotensive circulating volume restoration and to act as a mild calming agent. Unless the 257 mare is showing obvious signs of cardiac compromise, naloxone is not administered. 258 Broad spectrum antimicrobial coverage is initiated (K penicillin and gentamicin, 259 alternatively trimethoprim-sulfamethoxazole) for a minimum of five d. Analgesia and 260 anti-inflammatory therapy is provided by flunixin meglumine. When this is insufficient, 261 a constant rate infusion of lidocaine is given until 48 h following the last noted abdominal 262 pain. Hemostatic therapy is continued for 2 to 3 d, allowing ultrasonographic evidence of 263 the cessation of hemorrhage and stabilization of the hemorrhage site (if visible or 264 palpable) to be noted. The author avoids the use of oxytocin in post partum hemorrhage 265 mares, and is judicious with rectal evaluation. Uterine lavage, when attempted after 2 to 266 3 d, involves the establishment of a siphon and avoids distension of the uterus whenever 267 possible. Undue stress from any source is avoided. This is especially important with 268 mares protective of the foal, where procedures involving the foal are minimized and 269 absences will be avoided if at all possible. 270 An appropriate fluid plan following stabilization of the hypovolemic mare is to 271 provide a maintenance rate of polyionic intravenous fluids (2 ml/kg/h) until water intake 272 is deemed sufficient. A PCV that is low but stable is acceptable. The author considers a 273 462 PCV of 15% that is stable acceptable, however a blood cross match is initiated at this 274 point. The PCV will begin to slowly rise (1 to 2% daily) once hemorrhage ceases and the 275 bone marrow responds. Resorption of peritoneal blood (if present) aids in this increase. 276 Should the mare reach a PCV of 12% and continue to decrease, up to 20% of the 277 mare’s circulating volume should be replaced with whole blood over 2 to 3 h by 278 transfusion from a compatible donor. In this case, it should be expected that the PCV 279 will begin to slowly decrease again over a period of 2 to 3 d as the transfused red blood 280 cells are removed from circulation. 281 Useful drug dosages for postpartum mares are summarized in Table 1. 282 The Foal 283 Peripartum risk factors 284 Peripartum factors affecting the neonatal foal may be divided into three broad 285 categories. 286 Maternal health. Systemic illness with fever, gastrointestinal compromise 287 (potential for endotoxemia), and surgical manipulation are deleterious to the fetus. 288 Nutritional status also affects fetal health.1 289 Reproductive conditions of the mare. History of previous neonatal compromise, 290 known placental pathology (infection, thickening, separation), abnormalities of the birth 291 canal, vulvar discharge, and loss of colostrum prepartum alert the clinician to potential 292 neonatal difficulties. 293 Parturient events. The neonate can be affected by an abnormal gestation length, 294 prolonged labor, dystocia, premature placental separation, and premature rupture of the 295 umbilical cord. Meconium aspiration leads to hypoxic injury and pulmonary disease, 296 463 with presence of meconium in the amniotic fluid or amnion sometimes the only 297 indication of this event. 298 Resuscitation of the compromised neonate 299 Prior preparation in anticipation of an emergency is paramount to success. A 300 readily available collection of necessary equipment and drugs, kept within an easily 301 accessible and portable container aids in achieving a successful outcome. A list of drug 302 dose rates useful in resuscitation situations should be kept within the drug kit (Table 2). 303 Preparation of the foal for resuscitation includes drying and generally stimulating 304 the neonate, and clearance of respiratory and oral secretions by suctioning to maximize 305 the airway. It is convenient and safest to position the foal in lateral recumbency with any 306 rib fractures down. 307 ABCDE of resuscitation 308 Establishing a clear and consistent protocol for resuscitation of the neonate is 309 important when seeking to avoid delays in action during emergency situations (Table 3). 310 The order of activities can easily be remembered by the ABCDE protocol. Techniques, 311 drug dosages and break points determining changes in action may vary between 312 individual clinicians due to preference and case experience. The aim of establishing a 313 regular and sustainable cardiac and respiratory rhythm however is common to all 314 protocols. 315 Indications for referral 316 The normal newborn foal displays a fairly predictable progression from the time 317 of delivery to the onset of appropriate foal behavior and physiology (Table 4). 318 464 Significant deviation from these benchmarks strongly suggests that referral for advanced 319 care should be considered. 320 Evaluation of the at risk foal includes a physical examination and consideration 321 of the gestational history and laboratory values if available (Table 5). Although the foal 322 may appear normal initially, rapid deterioration is possible and subtle deviations in 323 physical findings and blood values may be the only indication of impending trouble. 324 Stabilization of the foal and preparation for referral 325 If the foal is showing signs of distress it may be prudent to transport the foal as 326 soon as possible even if separately from the mare. Send colostrum from the mare for 327 later administration and the placenta for examination if available. 328 If hypothermic, ensure the foal remains warm. Use blankets, insulated foal 329 covers, or provide external sources of heat such as warmed fluid bags. Avoid excessively 330 warming the hypovolemic foal as increasing circulation at the periphery can lead to 331 profound falls in blood pressure. 332 If breathing difficulties are present, place an intranasal oxygen cannula. Insert the 333 tip to the level of the eye socket. Portable oxygen tanks can be set to provide 5L oxygen 334 flow per minute. 335 Fluids should be administered if dehydration or hypovolemia are present. Half 336 the calculated deficit (deficit in liters = bodyweight in kg x % dehydration) can be given 337 rapidly prior to referral. Maintenance fluid rates for foals are higher than the adult horse, 338 being 5% to 10% of body weight daily, i.e., 2 to 4 ml/kg/hr. When calculating the 339 required maintenance rate, consider all sources of fluid intake for the foal to avoid over 340 hydrating the compromised foal. This is especially important if the foal is recumbent as 341 465 exceeding 10% of bodyweight can promote pulmonary edema formation. Glucose 342 supplementation (2.5% or 5% dextrose in polyionic fluids) can be given if blood glucose 343 levels are low, however rapid rehydration of the foal should always use non-glucose 344 containing fluids. Care must be exercised with the addition of glucose to fluids as over 345 supplementation results in hyperinsulinemia and subsequent worsening of hypoglycemia. 346 Placement of an indwelling feeding tube will aid in administration of colostrum as 347 well as provide a vehicle for continued feeding of the foal (if appropriate) during 348 transport to the referral facility should this be distant from the farm. Ensure the foal is 349 fed standing (if able to rise) or only when in sternal recumbency. Reflux of gastric 350 content is still possible with a correctly placed nasogastric tube. Avoid overfeeding the 351 sick foal: a useful rule of thumb is to feed 10% of the bodyweight of the foal as milk over 352 a 24 h period. Divide this amount into 12 equal feeds at two h intervals. Should colic or 353 nasogastric reflux occur post feeding, discontinue immediately. 354 Antimicrobial therapy should not be delayed in the foal suspected of sepsis (Table 355 2). Collection of a blood culture using aseptic technique before administration of 356 antimicrobials is desirable to improve chances of yielding the causative infectious agent. 357 This can be shipped with the foal for bacteriologic examination and antimicrobial 358 sensitivity analysis. 359 Anti-inflammatory treatments are also indicated in the foal that has sustained 360 physical trauma or is febrile. Lipid derived inflammatory mediators are important in the 361 pathophysiology of hypoxic ischemic encephalopathy (HIE) suggesting prompt use of 362 non-steroidal anti-inflammatory drugs (NSAIDs) and anti-oxidant therapies is warranted. 363 The NSAIDs vary in their potential for gastric mucosal and renal toxicity, especially if 364 466 used in the dehydrated patient; therefore care must be exercised in selection for the 365 compromised neonate. 366 If neurological dysfunction is present, control of cerebral edema and seizure 367 activity (if present) are indicated. Cerebral edema results from any traumatic, ischemic 368 or hypoxic insult to the neonate. The onset of signs of neurological dysfunction is 369 usually delayed, becoming apparent after a 24 to 48 h period of apparently normal 370 development. Often the only suggestions of impending problems are the gestational 371 history, parturient events, and subtle early neonatal behavioral abnormalities. Should 372 seizure activity ensue, control of seizure activity in the first instance is necessary to avoid 373 rapid exhaustion of the foal and secondary injuries predisposing to bacterial sepsis. 374 Placement of leg wraps and provision of padding adjacent to the foal will minimize 375 trauma. 376 If the foal is sufficiently medically stabilized and the owner is compliant, 377 transport to a referral facility is possible with the following considerations: 378 Timeliness. Nothing is worse than a referral too late. Increased costs of treatment 379 to the owner coupled with a decreased prognosis result in a loss to us all as a profession. 380 Owner financial resources. Hospitalization will be expensive. Complications are 381 provided at no extra cost. Continuous nursing care is expensive but imperative. 382 Ensure secure vascular access; if you place an intravenous catheter ensure that it will 383 remain in place with all attachments. This may be replaced with a longer-term catheter in 384 hospital. 385 467 History. Where possible, a written account encompassing treatment to the time of 386 arrival at the hospital. If the responsible person is not coming with the foal, encourage 387 the client to bring your billing/record sheets. 388 Up to date blood work is imperative. Blood collected before referral will likely 389 be repeated, to establish both a baseline and to gauge response to previous treatments. 390 Mare compliance. Is it necessary for the mare to accompany the foal? If so, will 391 she adjust to a hospital setting? 392 Summary 393 Peripartum hemorrhage in the mare may become a life-threatening emergency 394 depending on the structures involved and the extent of blood loss. Treatment of the mare 395 centers on promoting hemostasis and restoring circulating blood volume in a fashion that 396 does not excessively raise blood pressure and risk restarting hemorrhage. Many 397 established treatments are controversial. The neonatal foal may require resuscitation 398 following delivery as the result of gestational or parturient events. Although many 399 conditions can be managed on the farm, a thorough clinical exam should be performed to 400 identify those foals in need of specialist intervention. Appropriate stabilization and 401 preparation for transport and referral increase the probability of success. 402 References 403 1. 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Knutson JE, Deering JA, Hall FW, et al: Does intraoperative hetastarch 490 administration increase blood loss and transfusion requirements after cardiac 491 surgery? Anesthesia Analgesia 2000;90:801-807. 492 38. McCleane G: Intravenous lidocaine: an outdated or underutilized treatment for 493 pain? J Palliat Med 2007;10:798-805. 494 472 39. Doherty TJ, Frazier DL: Effect of intravenous lidocaine on halothane minimum 495 alveolar concentration in ponies. Equine Vet J 1998;30:300-303. 496 497 473 Table 1: Useful drug dosages for the postpartum mare Sedation: Care should always be exercised in the administration of sedation to the pregnant mare. Most agents cause hypotension which will exacerbate the negative effects of hypovolemia. Xylazine: 0.25 to 1 mg/kg iv or im. Potent hypotensive effects. Detomidine: 0.01 to 0.02 mg/kg iv or im. Less hypotensive potential than xylazine. Butorphanol: 0.01 to 0.02 mg/kg iv or im. Give as needed, may be repeated every 8 to 12 h. Effects will be attenuated where naloxone is administered concurrently. Acepromazine: 0.02 mg/kg im q 12h. Potent hypotensive agent, use with caution. Analgesia: Flunixin: 1 mg/kg iv q 12h Lidocaine: load with 1.3 mg/kg slow iv bolus of lidocaine 20% followed by 0.05 mg/kg/min iv as a constant rate infusion. May be conveniently made by adding 450 ml lidocaine 20% to a 3 L fluid bag and administering at 1 ml/kg/h. Hemostatic agents: ε-aminocaproic acid: 40 mg/kg iv load then 20 mg/kg iv q 6-8h. Administer in 1 L fluids over 15-30 min. Five or more doses may be required if hemorrhage ongoing. Yunnan baiyao: 8 mg/kg po q 6h. Administer 16 x 0.25g capsules in water as paste q 6h. Duration of treatment is highly variable, being 2 to 4 d. 474 Circulatory support: Naloxone: 0.01 to 0.02 mg/kg iv. Administered in initial treatment phase, may be repeated. Polyionic fluids: 2 ml/kg/h iv (maintenance rate). Continued throughout the period when fluid intake by other means deemed inadequate. Hypertonic saline: 2 to 4 ml/kg iv. Controversial due to potential for a rapid rise in blood pressure. Given during the initial fluid resuscitation period. Hetastarch: 6 to 10 ml/kg iv. Administered during the initial fluid volume restoration period only. 475 Table 2: Useful drug dosages for the foal. Antimicrobials: Duration of treatment is governed by clinical response. A minimum of five d should be administered in the absence of adverse reactions. K penicillin: 40000 to 50000 units/kg iv q 6h Ceftiofur sodium: 2 mg/kg im q 12h or 5 to 10 mg/kg iv q 6-12h Amikacin: 25 mg/kg iv q 24h Trimethoprim-sulfamethoxazole: 30 mg/kg po bid Seizure control and metabolic support: Diazepam 0.05 to 0.4 mg/kg iv. Short-acting control following acute onset of seizure activity. May repeat 2 to 3 times as required to establish control. Phenobarbital 4 to 10 mg/kg iv. Long-acting control useful when initial agent fails. May be repeated at 12 h intervals for continued control, or change to oral phenobarbital at 4 mg/kg po q 12h. Thiamine 10 mg/kg iv q 24h. Cerebral metabolic support. Useful in initial stages of hypoxic insult. Control cerebral edema and inflammation: Hypertonic saline 7 ml/kg iv as 3% solution. Shown to aid in control of cerebral edema. Useful in initial period following insult. 476 Mannitol 1 mg/kg iv as 20% solution. May repeat at 12 h intervals until appropriate mentation returns, often 2 to 3 d sufficient. Flunixin meglumine: 1 mg/kg iv q 12h. Continue while clinical signs evident. Ketoprofen: 2 mg/kg iv q 24h. As for flunixin. Less ulcerogenic potential. Control oxidative damage: Vitamin C 100 mg/kg iv q 24h. Useful in the initial stages following onset of cerebral compromise. Three d treatment or more may be required and this is safely administered. Vitamin E 20 iu/kg sc q 24h. Requires prolonged administration to reach therapeutic levels in central nervous system. Dimethyl sulfoxide 1 g/kg iv q 12h as 10% solution. Useful during period when ongoing damage is suspected to be occurring, often up to three d post insult. Respiratory stimulant Caffeine 10 mg/kg po load, then 2.5 mg/kg po q 6h. Continue until appropriate respiratory pattern is established. May cause hyperactivity and lower the seizure threshold in some foals. 477 Table 3: Resuscitation protocol for the compromised neonate. Airway Intubate by nasotracheal route with largest practical endotracheal tube Extend neck and twist as arytenoids reached to ease passing Size 8 to 10 mm suitable for average foals Pass tube to nares to minimize dead space Compress chest and palpate esophagus to ensure correct placement Breathing Respiratory arrest usually precedes cardiac arrest in the neonatal foal Establish rate of 8 to 10 breaths/minute with 1 second inspiration period Use 100% oxygen if available, however room air is acceptable The use of a self-inflating resuscitation bag with a pressure limiting valve (Ambu), or any other similar delivery device, will aid ventilation and avoid excessive inflation pressure Doxapram (controversial) at 0.5 mg/kg iv Circulation Thoracic compressions if HR less than 60, especially if less than 60 and not increasing Minimize interruptions (no longer than 10 seconds) Rapid compressions (aim for 100/minute) Establish vascular access if response is not immediately favorable 478 Drugs Usage and rationale based on experience and extrapolation Heart rate less than 60 and not increasing Continue compressions to distribute drugs Epinephrine at 0.02 mg/kg (0.5 to 1 ml of 1:1000 per 50 kg foal). Intratracheal dose 5 to 10x this, however absorption is poor Repeat every 3 to 5 minutes until response is noted Administer 10 ml/kg of a balanced electrolyte solution. A 2 to 4 ml/kg hetastarch bolus may be useful to rapidly expand circulating volume Avoid inducing hyperglycemia with dextrose containing solutions as resulting hyperinsulinemia is depressive Dobutamine at 3 to 40 μg/kg/min iv is useful to improve pulse pressure and peripheral perfusion Everything else Monitor foal progress Pupillary light responses: dilated pupils indicate lack of cerebral perfusion Stop when HR above 60 (pause 10 seconds max) Spontaneous breathing (pause 30 seconds) End point determination 479 Table 4: Times of importance to the neonatal foal. Sternal Recumbency: the foal should right itself and be able to remain sternal within 5 to 10 minutes of birth. Standing: within 60 minutes (range of 15 to 165 minutes). Compromised neonates tend to remain recumbent longer, further exposing themselves to pathogens. Suckle reflex: usually develops within 20 minutes of birth, although may be much sooner. Suckling: the foal should suckle the mare within 2 h (range 35 minutes to 7 h). Urination: first urination occurs at 6 h for colts, 10 h for fillies. Urine production: approximately 6 mL/kg/hr. Decreases may result from decreased fluid intake, increased losses or compromises in renal function. Obstruction or disruption due to rupture and uroperitoneum are possible in the compromised neonate, or one which sustained trauma during parturition. Defecation: foals display abdominal straining within the first few h after of birth, and pass meconium completely within 24 h. Colostrum stimulates GI motility. Any interference with GI motility will prolong passage of meconium increasing the likelihood of impaction. 480 Table 5: Examination of the neonatal foal. • Rectal temperature Appropriate neonatal range 99 °F to 101.5 ºF. Neonatal foals are unable to regulate body temperature to the same degree as older foals. • Cardiovascular system Appropriate neonatal heart rate (HR) range is between 70 to 120 beats per minute. HR is highly labile, however rate and rhythm is regular. Pulses are synchronous with the heart beat and easily palpable. Deviations may indicate arrhythmia (electrolyte abnormality, congenital cardiac anomaly). A murmur associated with a PDA can occur for the first few days of life. • Respiratory system Within the first hour of life, the respiratory rate (RR) of a normal foal can rise up to 80 breaths per minute. The RR decreases progressively over the next few days, with a subsequent range of 30 to 40 breaths per minute. Increased RR may indicate compromised pulmonary function, pain, excitement or fever. The magnitude of the thoracic excursion is indicative of the respiratory effort. Any decrease may indicate fatigue. Nostril flaring may be the only indication of increased respiratory effort. • Musculoskeletal system 481 Joint distension: indicative of sepsis, coagulopathy (hemarthrosis), trauma. • Integument Decubital ulcers indicate trauma, unseen seizure activity or the occurrence of prolonged recumbency. Pitting edema suggests hypoproteinemia or cardiac dysfunction. Icterus suggests sepsis, neonatal isoerythrolysis, or hepatic disease. Hemorrhage on the mucous membranes suggests sepsis, coagulopathy or direct trauma. • GI function Any occurrence of colic has the potential to indicate a life-threatening episode and should be thoroughly investigated. • Urinary function Acute renal failure may occur as the result of decreased in utero blood supply or be iatrogenic from nephrotoxic drug usage. Uroperitoneum results from a ruptured bladder, ruptured urachus or torn ureter. • Ocular examination Hyperemia of the sclera indicates birth trauma, sepsis, or coagulopathy. Entropion results from weight loss or dehydration leading to enophthalmia. Corneal opacity is the result of ulceration, a depressed blink response, lack of tear production, or exposure keratitis in the depressed neonate. 482 Anterior chamber: can reflect systemic inflammation and sepsis. Fibrin deposition (aqueous flare) and hypopyon may result. • Mentation and nervous function Hypoxic ischemic encephalopathy causes loss of affinity for the mare, generalized depression and a lack of vigorous suckling. Low level seizure activity may appear as muscle fasciculations, chewing fits, or unexplained cutaneous trauma. The menace response is absent from the neonate and is not an indication of vision. This reflex will take between 4 to 14 d to develop. HEMATOLOGY • Normal neonatal range (birth to 1 week): RBC range from 7.4 to 11.4 million cells/uL. WBC range from 4.9 to 13.6 thousand cells/uL. • Neutrophils (N): approximately 5500 cells/μL are present at birth with this increasing to 8000/μL within the first 12 h of life. • Lymphocytes (L): may decrease to approximately 1400 cells/μL within a few hours of birth, thereafter they increase to approximately 5000 cells/μL by 3 months of age. A transient decrease to below 1000 cells/μL may occur in some normal foals, but this may also indicate infection or immune compromise. SERUM CHEMISTRY 483 In the absence of established foal parameters in many laboratories, normal adult equine values are often used for assessment of neonatal foal health. • Serum electrolyte concentrations are maintained within a narrow range and do not differ substantially from established adult values. • Glucose is elevated compared to adults due to frequent suckling. Hypoglycemia is cause for concern as this may indicate of sepsis or decreased feeding activity. • Plasma protein levels at birth vary considerably between foals. • Serum creatinine and BUN are unreliable indicators of newborn foal renal performance as the placenta is primarily responsible for elimination of waste products; therefore an increase reflects placental dysfunction. However, BUN and creatinine may be initially elevated decreasing to adult levels by 3 to 5 d. • Total bilirubin may be elevated as mild icterus is common. Consider sepsis, isoerythrolysis or hepatic disease. • Creatine kinase is raised by muscle trauma from delivery. • Alkaline phophatase is elevated due to rapid growth in the neonate. • GGT elevations may be of colostral origin. • Fibrinogen is uniformly low in the healthy neonate (up to 200mg/dL). Elevated levels indicate in utero challenge with prenatal response. • IgG concentration: there is a strong association between the occurrence of sepsis and an immunoglobulin concentration less than 400mg/dL. 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