Chemical Restraint of Juvenile East African River Hippopotamus (Hippopotamus amphibius kiboko) at the San Diego Zoo ( 6-Sep-2001 )

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1 In: Zoological Restraint and Anesthesia, D. Heard (Ed.) Publisher: International Veterinary Information Service ( Ithaca, New York, USA. Chemical Restraint of Juvenile East African River Hippopotamus (Hippopotamus amphibius kiboko) at the San Diego Zoo ( 6-Sep-2001 ) P. J. Morris, B. Bicknese, D. Janssen, B. Loudis, A. Shima, M. Sutherland-Smith and L. Young San Diego Zoo, Department of Veterinary Services, San Diego, California, USA. Summary Chemical restraint and anesthesia of the hippopotamus has posed significant difficulties to the zoo/wildlife veterinarian due to the large size, amphibious habits, thick skin, and aggressive demeanor [1,2]. In a recent review of hippopotamus anesthesia methods, etorphine with or without xylazine or acepromazine was found to be the most commonly used drug combination for chemical restraint in this species [2]. This report summarizes the clinical data of 10 immobilizations of 1-2 year old river hippopotamus using a combination of detomidine and butorphanol (D-B). We have found that D-B produces profound sedation in this species sufficient to accomplish most noninvasive procedures. Animals can be aroused from D-B sedation if sufficiently stimulated. Supplemental ketamine given at 1 mg/kg i.v. increased the level of sedation in three of 10 cases where arousal from sedation was observe. In these cases, transient apneustia was associated with the administration of intravenous ketamine, but was not clinically significant. Supplemental oxygen was given at 8-15 l/min via nasal cannula, mask, or intubation to help prevent hypoxemia. Antagonism of D-B sedative effects is accomplished with intramuscular injections of a combination of either yohimbine and naltrexone (Y-N), or atipamezole and naltrexone (A-N). When employing this method of sedation, invasive procedures should only be attempted after induction of anesthesia provided by an inhalant anesthetic such as isoflurane via endotracheal intubation. Bradycardia and hypotension are predictable side effects resulting from the use of this combination. In all cases animals were relaxed and jaw tone was virtually nonexistent. Intubation of one juvenile river hippo was accomplished with an endotracheal tube size of 24 mm diameter, though a good assessment of the fit could not be made in this case. The tube functioned, but blow-by was observed during inhalant anesthesia. Introduction The family hippopotamidae contains two genera, the familiar Nile River hippopotamus and the pygmy hippopotamus. Adult Nile river hippopotamus (Hippopotamus amphibius) weigh between kg in body weight, males weighing more than females. Individuals can be up to 14.6 feet in length [3,4]. The river hippo is reported to be one of the most dangerous animals alive, killing more humans per year than the crocodile. The pygmy hippo (Choeropsis liberiensis) is much smaller than the river hippo. Adults typically weigh kg and reach a length of 5-6 feet in length. While smaller, pygmy hippos can also cause severe bites [3,5]. Both species of hippopotamus are highly aquatic, and care must be taken to prevent sedated hippopotamus from entering water to prevent accidental drowning. Results and Discussion Clinical observations made during sedation with D-B in juvenile hippos are summarized in Table 1. Animals were given a combination of detomidine HCl at mg/kg, and butorphanol tartrate at mg/kg via dart (Telinject or Daninject) with a 60 mm-long needle (Telinject or Daninject) into the skin fold of the neck. The time from darting until initial drug effects, recumbency, and total procedure length were recorded in each case. During the procedure, hippopotamus were sufficiently sedated to allow the authors to conduct a physical examination, including an oral exam, administer injectable agents, and collect blood samples from the ventral tail and/or cephalic veins. In one case sedation was sufficient to catheterize the cephalic vein, and to conduct wound care to a severe bite to the right rear leg involving deep structures. There were no deaths and no clinically significant adverse events observed during any of the sedation events. Bradycardia and hypopnea were observed intermittently during each of the 10 sedation events. Evidence of hypoxemia was observed using a portable oximeter.

2 Table 1. Summary chemical restraint and dose data from a D-B sedated juvenile river hippopotamus 1-2 years of age collected over several sedation events. All doses are reported in mg/kg body weight. All immobilization events are reported in minutes after D-B intramuscular (dart) injection (n=10 individual sedations; SEM = standard error of the mean). Age (yrs) Wt (kg) D B A Y N I R P A Average SEM D= detomidine dose, B= butorphanol dose, A= atipamezole dose, Y= yohimbine dose, N= naltrexone dose, I= time after darting until initial effects observed, R= time after darting until recumbency, P= time after darting until administration of the antagonists, A= time after administration of antagonists until the animal regained ambulatory ability. Restraint Before planning a chemical restraint procedure, it is important to realize that some procedures can be performed without anesthesia. With proper facilities and training, some of these animals can be habituated to medically-oriented routines [6,7]. A concrete or dirt pen with stout walls high enough to discourage an animal from attempt to climb out are required for containment. In addition to avoiding access to water, it is important to be very familiar with the available housing facilities before attempting to sedate a hippo. It is inappropriate to attempt immobilization in any situation where the animal can gain access to a pool after darting [2]. Chemical Restraint The most common chemical restraint agent used in river hippos has been etorphine (1-5 mcg/kg, or 2-6 mg total dose), with or without xylazine (67-83 mcg/kg, or approximately 100 mg per adult) or acepromazine as a component with etorphine in the combination marketed in the United Kingdom as Immobilon [2,8]. In our practice, ketamine at approximately 1 mg/kg has been used to immobilize pygmy hippopotamus on several occasions, mainly for tusk trims. In general, anesthesia went well with this combination, and animals tended to recover quickly and without incident. Anesthetic agents are typically injected via dart into a skin fold of the neck (Fig. 1). A needle of approximately 60 mm is adequate to pierce the thick hide to deliver an i.m. injection [2]. Figure 1. A young female hippopotamus has been immobilized to treat an actively bleeding leg wound. A plastic bag has been fashioned into a mask to provide supplemental oxygen during the procedure. Higher oxygen flow rates are required when using this technique in order to avoid the buildup of expired CO 2. Relative hemoglobin saturation trends are being monitored by placing an oximeter probe on the ear. The animal was maintained in lateral recumbency on a cushioned mat to reduce the potential for pressure-induced nerve injury. Neck folds used as preferred sites for injection of intramuscular drugs can be seen as well. - To view this image in full size go to the IVIS website at - Because of reported difficulties associated with the use of etorphine [2,9], young river hippos acquired by the San Diego Zoo were used in a pilot study to evaluate the use of detomidine and butorphanol as a potential sedative agent combination in this species. Surprisingly, a combination of 0.15 mg/kg butorphanol tartrate with mg/kg detomidine mixed together and given as a single injection i.m. produced profound sedation and recumbency suitable to conduct physical exams, phlebotomy and other routine procedures in three young river hippos [10]. The D-B protocol was used to immobilize a 28 year-old female hippopotamus for a dermatologic evaluation. In this case, 40 mg of detomidine and 60 mg of butorphanol were given i.m. [11]. The result was recumbency, but incomplete sedation. Access was gained to this animal through protected contact with the animal lying recumbent in a sturdy chute during the medical investigation. After 65 minutes of recumbency the animal stood without warning. Although in this case the weight estimate was 950 kg, it is more likely that an adult female hippopotamus would be approximately 1500 kg. At 1500 kg, the resulting doses would have been approximately mg/kg of detomidine and 0.04 mg/kg butorphanol, well below the doses we have used in young river hippos. This result is testimony to the potency of an alpha2-adrenergic agent and butorphanol in this species. This sedative combination can be antagonized using yohimbine at 0.3 mg/kg with naltrexone at 0.5 mg/kg or atipamezole at 5

3 mg atipamezole per each 1 mg detomidine with naltrexone at 0.5 mg/kg (Morris, unpublished results). In our practice these agents are mixed into one syringe and administered i.m. to avoid adverse reactions associated with intravenous atipamezole [12]. The D-B protocol reported here is, in the author s opinion, the combination of choice for hippopotamus. In addition to the beneficial attributes of D-B sedation in hippopotamus, most practitioners are unable to obtain etorphine on any kind of regular basis. For the interested reader, selected case reports of anesthetic events in hippopotamus are listed in the references [1,5,8,11,13-16]. Venous access is a problem in this species due to the thick skin. Venous access can be accomplished with a superficial vein lying along the medial aspect of the antebrachium and with superficial ear veins [2,9] (Fig. 2). Figure 2. The medial cephalic vein is difficult to catheterize, but can be used for venous access. In this case, a blood replacement product is being given to help fight the effects of blood loss during triage of an actively bleeding leg wound. - To view this image in full size go to the IVIS website at - Ketamine administered at 1 mg/kg i.v. has produced additional sedation in one young river hippo sedated in our practice to treat a leg wound. Apneustia was observed in this case after the administration of intravenous ketamine, but oximetry remained unchanged. Within five minutes of ketamine administration, spontaneous respiration resumed (Morris, unpublished results). Blood can be obtained from the tail laterally at the base through a blind stick, but is not a reliable site for phlebotomy or catheterization. The caudal tail artery was not a reliable source for blood collection in the four animals used to evaluate the D-B protocol. Ultrasound imaging can be useful to locate superficial blood vessels if none can be seen or balloted in the ear or front leg. Patient Monitoring It is often difficult to monitor vital signs in river hippopotamus, mainly due to the fact that the thick hide and large size tends to complicate visualization of respirations and cardiac auscultation. A respirometer attached to an endotracheal tube inserted into a nostril helps to monitor spontaneous respiration. Relative hemoglobin saturation values can be obtained by placing an oximeter probe on the pinna, the tongue, or the vulva/prepuce. An ECG also allows monitoring of the heart rate, but interference often obscures the electrical signal emitted by the heart (Morris, unpublished results). Venous blood gases measured in 5 separate sedation events using D-B in a 1.5 year old juvenile river hippopotamus are summarized in Table 2. In the cases described here, evidence of hypoxemia was noted early on in the procedures. Table 2. Summary venous blood gas data on a 1.5 year old juvenile pygmy hippo (average = top line, SEM = bottom line, n= 5 immobilizations). Body temp (F) ph PCO 2 PO 2 Calc HCO 3 Calc BEecf Calc SO 2 Calc TCO 2 Average SEM In the author s experience hypoxemia is commonly seen when sedating zoological species, and is an expected event during recumbency of large animals [17]. The effects of sedation and recumbency tend to result in hypoventilation. In most cases this will result in hypoxemia and hypercapnea. Hypercapnea was evident during sedation in these cases, but this is a typical finding in the author s experience with most sedation events in large-bodied zoological species. Because prolonged hypercapnea can lead to metabolic problems the author uses a practical approach to dealing with hypercapnea; as a general rule of thumb, sedations are limited to less than an hour total duration from darting to administration of antagonists. In the author s experience the vast majority of routine procedures can be accomplished in this time. If sedation is required beyond an hour it is advisable to intubate and maintain the animal on inhalant anesthesia. Once this is accomplished, hypercapnea can usually be reversed by assisted ventilation efforts.

4 Table 3a. Summary of serum chemistry results of river hippos sedated with D-B (SEM in parenthesis) (n=10) Na (1.5) K 4.6 (0.3) Cl 98.5 (1.3) CO (0.5) Anion 10.8 (0.5) Ca 10 (0.2) PO (0.5) Alk 220 (68.7) AST (14.8) ALT 19.8 (0.9) LDH (205.6) CPK (1598.1) GGT 27.5 (1.3) Glu (16.8) BUN 18 (1.6) CR 1.3 (0.1) UA 0.4 (0.0) TP 6.9 (0.3) Alb 4.3 (0.2) Tbili 0.9 (0.1) Chol 10.0 (2.7) Trig 21.3 (6.3) Mg 2.0 (0.1) Amy 3.3 (0.5) Table 3b. Summary hematology results of river hippos sedated with D-B (average = top line, SEM bottom line, n=10) WBC RBC Hb PCV MCV MCH MCHC Plt PP Fib nrb Hem Seg Ban Juy Lymph Monos Eos Basos In the author s experience hypoxemia is commonly seen when sedating zoological species, and is an expected event during recumbency of large animals [17]. The effects of sedation and recumbency tend to result in hypoventilation. In most cases this will result in hypoxemia and hypercapnea. Hypercapnea was evident during sedation in these cases, but this is a typical finding in the author s experience with most sedation events in large-bodied zoological species. Because prolonged hypercapnea can lead to metabolic problems the author uses a practical approach to dealing with hypercapnea; as a general rule of thumb, sedations are limited to less than an hour total duration from darting to administration of antagonists. In the author s experience the vast majority of routine procedures can be accomplished in this time. If sedation is required beyond an hour it is advisable to intubate and maintain the animal on inhalant anesthesia. Once this is accomplished, hypercapnea can usually be reversed by assisted ventilation efforts. In field situations, oxygen can be supplemented via soft rubber cannula inserted into one nostril, or a plastic bag fashioned into a mask. Care must be taken to avoid rebreathing with a mask by setting the oxygen flow rate up high enough to significantly reduce rebreathing. A recent case of a young female hippo sedated to evaluate a leg wound is used to illustrate oxygen supplementation and oximetry trend monitoring (Fig. 1). Invasive procedures require supplemental anesthesia. For these cases endotracheal intubation is indicated. For adult hippopotamus cuffed endotracheal tubes between mm diameter are recommended, using an oxygen flow rate of approximately 15 liters/min [2]. Isoflurane has been used to supplement anesthesia in hippopotamus for various invasive procedures [9]. Propofol at approximately mcg/kg/min would also be theoretically useful as a supplement anesthetic agent to perform invasive procedures, but spontaneous arousal of a hippopotamus during a procedure would be an extremely dangerous event. In addition to this, intravenous access is difficult to achieve in this species, and once established, is easily lost if a limb is moved. Therefore, until more is reported on the use of propofol for hippos, isoflurane for maintenance anesthesia would be safest for the animal and personnel in attendance. Recovery is fairly straight forward, since the hippopotamus is built low to the ground, there is usually little harm associated with multiple attempts to rise. Access to a pool should be given only once the signs of sedation have abated. In the cases sedated with detomidine/butorphanol, animals were allowed access to a pool two hours after recovery provided there was no outward sign of sedation. Recurrent sedation following antagonism in D-B cases has not been encountered in any of the 8 events recorded in four river hippos at the San Diego Zoo.

5 Acknowledgement The author would like to thank the co-authors and the registered veterinary technicians, clinical pathology technicians, animal management staff and keepers of the San Diego Zoo who were involved with the sedation procedures described in this article. Finally, the author would like to thank Dr. Victoria Clyde for feedback on the use of D-B in an adult nile hippopotamus at the Milwaukee Zoo. References 1. Flach EJ, Furrokh IK, Thornton SM, et al. Caesarean section in a pygmy hippopotamus (Choeropsis liberiensis) and the management of the wound. Vet Rec 1998; 143(22): Loomis MC, Ramsay EC. Anesthesia for Captive Nile Hippopotamus. In: Fowler ME and Miller RE, eds. Zoo & Wild Animal Medicine: Current Therapy 4. Philadelphia: WB Saunders Co, 1999; Boitani L, Bartoli S. Hippopotamus (plate 355) and Pygmy Hippopotamus (plate 354). In: Anderson S, ed. Simon and Schuster s Guide to Mammals. New York: Simon and Schuster Co, 1982; plates Taylor G, Greenwood A. Hippopotamidae. In: Fowler ME ed. Zoo & Wild Animal Medicine. Philadelphia: WB Saunders Co, 1986; Reed GT. Immobilization of two captive adult Nile hippo (Hippopotamus amphibius). In: Proceedings of the Am Assoc Zoo Vet 1978; Dumonceaux GA, Burton MS, Ball RL, et al. Veterinary procedures facilitated by behavioral conditioning and desensitization in reticulated giraffe (Giraffa camelopardalis) and Nile hippopotamus (Hippopotamus amphibius). In: Proceedings of the Am Assoc Zoo Vet 1998; Krueger S, Shellabarger W, Reichard T. Hippopotamus training: Implications for veterinary care. In: Proceedings of the Am Assoc Zoo Vet 1996; Pearce PC, Knight J, Gustavo C, et al. Immobilization of a pygmy hippopotamus (Choeropsis liberiensis). J Zoo Anim Med 1985; 16(3): Ramsay EC, Loomis MR, Mehren KG, et al. Chemical restraint of the Nile hippopotamus (Hippopotamus amphibius) in captivity. J Zoo Wildl Med 1998; 29(1): Morris PJ. Recent developments in anesthesia of exotic ungulates. In: Proceedings of the North American Veterinary Conference 1996; Clyde VL, Wallace RS, Pocknell AM. Dermatitis caused by group G beta-hemolytic Streptococcus in Nile hippos (Hippopotamus amphibius). In: Proceedings of the Am Assoc Zoo Vet 1998; Jalanka HH, Roeken BO: The use of medetomidine, medetomidine-ketamine combinations, and atipamezole in nondomestic mammals: A review. J Zoo Wildl Med 1990; 21: Bishop L, Stoskopf MK. Immobilization of two captive Nile hippo (Hippopotamus amphibius). J Zoo Anim Med 1978; 9 (3): Boever WJ, Miller RE. Repair of rectal stricture and prolapse in a pygmy hippopotamus (Choeropsis liberiensis). J Zoo Anim Med 1983; 14(2): Robinson PT. A history of the pigmy hippo in captivity. J Zoo Anim Med 1971; 2(2): Weston HS, Fagella AM, Burt L, et al. Immobilization of a pygmy hippopotamus (Choeropsis liberiensis) for the removal of an oral mass. In: Proceedings of the Am Assoc Zoo Vet 1996; Hornof, WJ, Dunlop CL, Prestage R and Amis TC. Effects of lateral recumbency on regional lung function in anesthetized horses. AJVR 1986; 47: All rights reserved. This document is available on-line at Document No. B