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Nalmefene

The Elephant Formulary
2003-06 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D.
Published by Elephant Care International -
www.elephantcare.org


Elephant specific information, if available, is in blue.

Technical information to be added

 

Elephants:

a) Carfentanil at 2.10.3 g/kg as a single IM injection in captive elephants was reversed with nalmefene, at a mean ratio for nalmefene/carfentanil of 26:1 (Raath, 1999).

 

b) Four juvenile African elephants immobilized with carfentanil (2.4 g/kg based on estimated weights) were reversed with nalmefene.  One was given nalmefene 166.7 g/kg both IV and SC.  Two were given nalmefene IV and IM.  The dosage was 88.9 g/kg IV and IM in one elephant and 53.3 g/kg IV and IM in the other.  One elephant was given nalmefene (88.9 g/kg IV) followed by diprenorphine (8.9 g/kg IM). Reversal was rapid and uneventful and no cases of renarcotization were noted (Schumacher, et.al. 1995).

 

c) To reverse carfentanil, give nalmefene at 26 times the carfentanil dose (Kock, 1993).

 

d) Seventeen African elephants immobilized with carfentanil (2.10.3 g/kg) were reversed with nalmefene (n=13), diprenorphine (n=2), or diprenorphine and nalmefene (n=2).  Antagonists were administered IV and IM or IV and SC.  Sixteen of 17 elephants were standing in 2.91.4 minutes.  Further info below (Jacobson, et.al. 1988).

 

e) Fourteen African elephants immobilized with etorphine or carfentanil were reversed with nalmefene. See text below (Jacobson et.al. 1987).

 

Elephant References:

a) Raath,J.P., 1999. Relocation of African elephants. In: Fowler,M.E. and Miller,R.E. (Editors), Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders, Philadelphia, PA, USA pp. 525-533

b) Schumacher,J., Heard,D.J., Caligiuri,R., Norton,T., and Jacobson,E.R. 1995. Comparative effects of etorphine and carfentanil on cardiopulmonary parameters in juvenile African elephants (Loxodonta africana).  Journal of Zoo and Wildlife Medicine 26:(4):503-507 
Abstract: Fourteen African elephants (Loxodonta africana) were immobilized with either etorphine hydrochloride (3.2
0.5 g/kg i.m.) or carfentanil citrate (2.4 g/kg i.m.). Induction time with etorphine was significantly longer (30 21 min) than with carfentanil (8 2 min).  Immediately following immobilization all elephants were placed in lateral recumbency and respiratory rate, heart rate, and rectal body temperature were monitored every 5 min throughout the immobilization period.  Arterial blood samples, collected from an auricular artery, were taken 10 min after immobilization and every 15 min thereafter for up to 1 hr.  At the first sampling, mean values for arterial blood gas variables for etorphine immobilized elephants were pHa, 7.29 0.03; PaCO2, 53.4 5.2 mmHg; PaO2, 71.8 13.8 mmHg; standard base excess (SBE), -1.6 2.9 mEq/L; and HCO3, 25.7 2.7 mEq/L. After 1 hr of immobilization, mean arterial blood gas values were pHa, 7.32 0.06; PaCO2 , 57.2 9.6 mm Hg; and PaO2 , 53.8 10.5 mm Hg; SBE, 2.7 1.4 mEq/L; and HCO3-, 30.6 1.6 mEq/L.

 

For carfentanil immobilized elephants, blood gas values at the first time of collection were pHa, 7.28 0.04; PaCO2, 52.1 2.8 mmHg; PaO2, 78.3 14.7 mmHg; SBE, -2.3 24 mEq/L; and HCO3-, 24.3 2.1 mEq/L.  Sixty minutes after the first sampling, blood gas values of one elephant were pHa, 7.38; PaCO2, 48.7 mmHg; PaO2, 52 mmHg; SBE, 3.4 mEq/L, and HCO3-, 28.8 mEq/L.  Over time there was a progressive decline in arterial PO2 in all elephants.  It is concluded that elephants immobilized with either etorphine HCl or carfentanil developed hypoxemia (PaO2 < 60 mmHg) after 30 min of immobilization.  It is recommended that the administration of one of these opioid drugs be accompanied by supplemental oxygen, or followed by an inhalant anesthetic in 100% oxygen for prolonged procedures.  Diprenorphine or nalmefene reversal was rapid and uneventful in both the etorphine and carfentanil group.  No cases of renarcotization were noted. Additional excerpt: All elephants in the etorphine group (n=8) received diprenorphine at a mean dosage of 8.3 1.1 g/kg IV. Two elephants in the carfentanil group (n=6) were administered diprenorphine at a dosage of 8.9 g/kg IV and IM.  Three elephants in this group received nalmefene hydrochloride.  One of the three elephants was given nalmefene 166.7 g/kg both IV and SC. Two of the three elephants were given nalmefene IV and IM. The dosage was 88.9 g/kg IV and IM in one elephant and 53.3 g/kg IV and IM in the other. One elephant in the carfentanil group was administered nalmefene (88.9 g/kg IV) followed by diprenorphine (8.9 g/kg IM).

 

c) Kock,R.A., Morkel,P., and Kock,M.D., 1993. Current immobilization procedures used in elephants. In: Fowler,M.E. (Editor), Zoo and Wild Animal Medicine Current Therapy 3. W.B. Saunders Company, Philadelphia, PA, USA pp. 436-441

d) Jacobson,E.R., Kollias,G.V., Heard,D.J., and Caligiuri,R. 1988. Immobilization of African elephants with carfentanil and antagonism with nalmefene and diprenorphine. Journal of Zoo Animal Medicine 19:1-7  Abstract: Sixteen African elephants (Loxodonta africana) were immobilized with single i.m. injections of carfentanil citrate (2.1 0.3 g/kg body weight).  All elephants were laterally recumbent in 10.1 3.7 min.  An additional elephant which received 1.4 g /kg carfentanil did not become recumbent and additional carfentanil was required for immobilization.  Following immobilization, nine elephants were maintained in lateral recumbency by administration of multiple i.v. injections of carfentanil, one elephant received a single i.v. dose of ketamine hydrochloride, and four were intubuted and administered 1-1.5% halothane in oxygen.  Because a short duration of immobilization was desired, three elephants were not given additional drugs.  The duration of immobilization ranged from 4 to 187 min.  Following a variety of medical and surgical procedures, 13 elephants received nalmefene hydrochloride, two elephants received diprenorphine, and two elephants received both diprenorphine and nalmefene; antagonists were administered either i.v. and i.m. or i.v. and s.c.  Sixteen of 17 elephants were standing in 2.9 1.4 min; the standing time of one elephant was not recorded. See also nalmefene monograph.

e) Jacobson,E.R., Heard,D.J., Caligiuri,R., and Kollias,G.V.  1987. Physiologic effects of etorphine and carfentanil in African elephants. Proc.1st.Intl.Conf.Zool.Avian Med. Pages: 525-527 Abstract: (Full text): The effects of etorphine hydrochloride and carfentanil citrate on blood pressure, heart rate, respiration and body temperature were determined in a group of captive African elephants (Loxodonta africana).  Fourteen African elephants, weighing 450 kg to 4000 kg, divided into 2 groups of 6 and 8 elephants each, received either etorphine hydrochloride (2.9 0.7 g/kg of body weight; mean SD) or carfentanil citrate (2.0 0.2 g/kg of body weight) respectively. The mean time for lateral recumbency in elephants which received etorphine was 31 9.1 minutes while the mean time for lateral recumbency in elephants which received carfentanil was 10.3 4.1 minutes.  Following immobilization, a 18 gauge catheter was inserted into an auricular artery, the catheter connected to a pressure transducer system and systolic, diastolic, and mean arterial pressures were monitored by use of a multichannel oscilloscope.  Systolic, diastolic, mean arterial pressures, heart rate, respiration, and temperature were recorded every 5 minutes over a 45 to 60 minute period.  Elephants were maintained in lateral recumbency over the period of monitoring by intravenous injections of either etorphine or carfentanil. 

Following immobilization with etorphine, mean physiological values for elephants were: systolic pressure, 229 33 mm Hg; diastolic pressure, 141 30 mm Hg; mean arterial pressure, 177 30 mm Hg; heart rate 64 10 beats/minute; respiratory rate 10 4 breaths/minute; body temperature, 97 2F.  Mean physiological values at the final time period of monitoring prior to antagonism were: systolic pressure, 217 40 mm Hg; diastolic pressure, 147 36 mm Hg; mean arterial pressure, 176 38mm Hg; heart rate 77 13 beats/minute; respiratory rate 12 1 breaths/minute; body temperature, 98 2F.  Immediately following the last recording, all 8 elephants received the experimental opioid antagonist, nalmefene hydrochloride, administered at 38 11 g/kg of body weight given both subcutaneously and intravenously.  The mean standing time following administration of nalmefene was 1.4 0.7 minutes.

Immediately following immobilization with carfentanil, mean physiological values for elephants were: systolic pressure, 232 28 mm Hg; diastolic pressure, 148 14 mm Hg; mean arterial pressure, 183 24 mm Hg; heart rate 57 11 beats/minute; respiratory rate 11 3 breaths/minute; body temperature, 99 1F.  Mean physiological values at the final time period of monitoring prior to antagonism were: systolic pressure, 224 29 mm Hg; diastolic pressure, 146 13 mm Hg; mean arterial pressure, 179 18mm Hg; heart rate 65 11 beats/minute; respiratory rate 12 1 breaths/minute; body temperature, 99 1F. Immediately following the last recording, all 6 elephants received the opioid antagonist, nalmefene hydrochloride administered at 62 17 g/kg of body weight given both subcutaneously and intravenously.  The mean standing time following administration of nalmefene was 2.6 1.6  minutes.

The results of this study indicated that both etorphine and carfentanil resulted in high blood pressure over the duration of the period of monitoring.  Based upon these findings, both etorphine hydrochloride and carfentanil citrate are not recommended as the primary agent in performing major invasive surgical procedures in African elephants.

See also:

Lance,W.R. 1991. New pharmaceutical tools for the 1990's. Proceedings of the American Association of Zoo Veterinarians 354-359

 

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