Research Paper| Volume 48, ISSUE 1, P65-73, January 2021

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Evaluation of intramuscular sodium nitroprusside injection to improve oxygenation in white-tailed deer (Odocoileus virginianus) anesthetized with medetomidine–alfaxalone–azaperone

Published:November 06, 2020DOI:



      In ungulates, α2-adrenergic agonists can decrease oxygenation possibly through alteration of pulmonary perfusion. Sodium nitroprusside can decrease pulmonary vascular resistance (PVR) and increase cardiac output ( Q ˙ t ) through vasodilation. The objective was to determine if sodium nitroprusside would improve pulmonary perfusion and attenuate the increased alveolar–arterial (a–a) gradient resulting from medetomidine–azaperone–alfaxalone (MAA) administration.

      Study design

      Prospective, randomized, crossover study with a 2 week rest period.


      A group of eight adult female captive white-tailed deer (Odocoileus virginianus).


      Deer were administered MAA intramuscularly (IM), and auricular artery and pulmonary artery balloon catheters were placed. Deer spontaneously breathed air. Saline or sodium nitroprusside (0.07 mg kg–1) were administered IM 40 minutes after MAA injection. Heart rate (HR), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), pulmonary artery occlusion pressure (PAOP), right atrial pressure (RAP), Q ˙ t , arterial pH, PaCO2 and PaO2 were obtained immediately before nitroprusside injection (baseline) and 5, 10 and 15 minutes afterwards. Mixed venous blood samples were obtained at baseline and at 5 minutes. Systemic vascular resistance (SVR), PVR, intrapulmonary shunt fraction ( Q ˙ s / Q ˙ t ), a–a gradient, oxygen delivery ( D ˙ O2) and oxygen extraction ratio (O2ER) were calculated. Statistical analysis was performed with repeated measures analysis of variance with correction factors. A p value < 0.05 was considered significant.


      With nitroprusside, MAP, MPAP, PAOP, RAP, SVR and O2ER significantly decreased and HR, Q ˙ t and D ˙ O2 increased compared with baseline and between treatments. There was a significant decrease in PVR and a–a gradient and increase in PaO2 compared with baseline and saline treatment. Changes were not sustained.

      Conclusions and clinical relevance

      Nitroprusside temporarily changed hemodynamic variables, increased PaO2 and decreased a–a gradient. Nitroprusside possibly led to better pulmonary perfusion of ventilated alveoli. However, IM nitroprusside at this dose is not recommended because of severe systemic hypotension and short action.


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        • Adam M.
        • Raekallio M.R.
        • Vainio O.M.
        Sedative effect of intramuscular medetomidine with and without vatinoxan (MK-467), and its reversal with atipamezole in sheep.
        Vet Anaesth Analg. 2018; 45: 788-793
        • Adam M.
        • Huuskonen V.
        • Raekallio M.R.
        • et al.
        Cardiopulmonary effects of vatinoxan in sevoflurane-anaesthetised sheep receiving dexmedetomidine.
        Vet J. 2018; 238: 63-69
        • Allen S.J.
        • Drake R.E.
        • Katz J.
        • et al.
        Lowered pulmonary arterial pressure prevents edema after endotoxin in sheep.
        J Appl Physiol. 1987; 63: 1008-1011
        • Benitz W.E.
        • Rhine W.D.
        • Van Meurs K.P.
        • Stevenson D.K.
        Nitrovasodilator therapy for severe respiratory distress syndrome.
        J Perinatol. 1996; 16: 443-448
        • Bixler T.J.
        • Gott V.L.
        • Gardner T.J.
        Reversal of experimental pulmonary hypertension with sodium nitroprusside.
        J Thorac Cardiovasc Surg. 1981; 81: 537-545
        • Caulkett N.A.
        • Cribb P.H.
        • Duke T.
        Cardiopulmonary effects of medetomidine-ketamine immobilization with atipamezole reversal and carfentanil-xylazine immobilization with naltrexone reversal: a comparative study in domestic sheep (Ovis ovis).
        J Zoo Wildl Med. 1994; 25: 376-389
        • Caulkett N.A.
        • Duke T.
        • Cribb P.H.
        Cardiopulmonary effects of medetomidine-ketamine in domestic sheep (Ovis ovis) maintained in sternal recumbency.
        J Zoo Wildl Med. 1996; 27: 217-226
        • Celly C.S.
        • McDonell W.N.
        • Black W.D.
        • Young S.S.
        Cardiopulmonary effects of clonidine, diazepam and the peripheral alpha 2 adrenoceptor agonist ST-91 in conscious sheep.
        J Vet Pharmacol Ther. 1997; 20: 472-478
        • Celly C.S.
        • McDonell W.N.
        • Young S.S.
        • Black W.D.
        The comparative hypoxaemic effect of four α2 adrenoceptor agonists (xylazine, romifidine, detomidine and medetomidine) in sheep.
        J Vet Pharmacol Ther. 1997; 20: 464-471
        • Celly C.S.
        • Atwal O.S.
        • McDonell W.N.
        • Black W.D.
        Histopathologic alterations induced in the lungs of sheep by use of alpha2-adrenergic receptor agonists.
        Am J Vet Res. 1999; 60: 154-161
        • Cornet A.D.
        • Hofstra J.J.
        • Swart E.L.
        • et al.
        Sildenafil attenuates pulmonary arterial pressure but does not improve oxygenation during ARDS.
        Intensive Care Med. 2010; 36: 758-764
        • Einwaller J.
        • Painer J.
        • Raekallio M.
        • et al.
        Cardiovascular effects of intravenous vatinoxan (MK-467) in medetomidine–tiletamine–zolazepam anaesthetised red deer (Cervus elaphus).
        Vet Anaesth Analg. 2020; 47: 518-527
        • Fahlman A.
        • Caulkett N.
        • Arnemo J.M.
        • et al.
        Efficacy of a portable oxygen concentrator with pulsed delivery for treatment of hypoxemia during anesthesia of wildlife.
        J Zoo Wildl Med. 2012; 43: 67-76
        • Fahlman A.
        • Caulkett N.
        • Woodbury M.
        • et al.
        Low flow oxygen therapy from a portable oxygen concentrator or an oxygen cylinder effectively treats hypoxemia in anesthetized white-tailed deer (Odocoileus virginianus).
        J Zoo Wildl Med. 2014; 45: 272-277
        • Fan F.-C.
        • Kim S.
        • Simchon S.
        • et al.
        Effects of sodium nitroprusside on systemic and regional hemodynamics and oxygen utilization in the dog.
        Anesthesiology. 1980; 53: 113-120
        • Friederich J.A.
        • Butterworth J.F.
        Sodium nitroprusside: twenty years and counting.
        Anesth Analg. 1995; 81: 152-162
        • Graham R.
        • Skoog C.
        • Macedo W.
        • et al.
        Dopamine, dobutamine, and phentolamine effects on pulmonary vascular mechanics.
        J Appl Physiol Respir Environ Exerc Physiol. 1983; 54: 1277-1283
        • Haskins S.
        • Pascoe P.J.
        • Ilkiw J.E.
        • et al.
        Reference cardiopulmonary values in normal dogs.
        Comp Med. 2005; 55: 156-161
        • Hottinger D.G.
        • Beebe D.S.
        • Kozhimannil T.
        • et al.
        Sodium nitroprusside in 2014: a clinical concepts review.
        J Anaesthesiol Clin Pharmacol. 2014; 30: 462-471
        • Jaeger A.T.
        • Pypendop B.H.
        • Ahokoivu H.
        • Honkavaara J.
        Cardiopulmonary effects of dexmedetomidine, with and without vatinoxan, in isoflurane-anesthetized cats.
        Vet Anaesth Analg. 2019; 46: 753-764
        • Kallio-Kujala I.J.
        • Raekallio M.R.
        • Honkavaara J.
        • et al.
        Peripheral α2-adrenoreceptor antagonism affects the absorption of intramuscularly coadministered drugs.
        Vet Anaesth Analg. 2018; 45: 405-413
        • Kästner S.B.R.
        A2-agonists in sheep: a review.
        Vet Anaesth Analg. 2006; 33: 79-96
        • Kästner S.B.R.
        • Ohlerth S.
        • Pospischil A.
        • et al.
        Dexmedetomidine-induced pulmonary alterations in sheep.
        Res Vet Sci. 2007; 83: 217-226
        • Lodato R.F.
        • Michael J.R.
        • Murray P.A.
        Multipoint pulmonary vascular pressure-cardiac output plots in conscious dogs.
        Am J Physiol. 1985; 249: H351-H357
        • Mathieu A.
        • Caulkett N.
        • Stent P.M.
        • Schwantje H.M.
        Capture of free-ranging mule deer (Odocoileus hemionus) with a combination of medetomidine, azaperone, and alfaxalone.
        J Wildl Dis. 2017; 53: 296-303
        • Mich P.M.
        • Wolfe L.L.
        • Sirochman T.M.
        • et al.
        Evaluation of intramuscular butorphanol, azaperone, and medetomidine and nasal oxygen insufflation for the chemical immobilization of white-tailed deer, Odocoileus virginianus.
        J Zoo Wildl Med. 2008; 39: 480-487
        • Naeije R.
        • Lejeune P.
        • Leeman M.
        • et al.
        Pulmonary arterial pressure-flow plots in dogs: effects of isoflurane and nitroprusside.
        J Appl Physiol. 1987; 63: 969-977
        • Pagani M.
        • Vatner S.F.
        • Braunwald E.
        Hemodynamic effects of intravenous sodium nitroprusside in the conscious dog.
        Circulation. 1978; 57: 144-151
        • Pon K.
        • Caulkett N.
        • Woodbury M.
        Efficacy and safety of a medetomidine-azaperone-alfaxalone combination in captive white-tailed deer (Odocoileus virginianus).
        J Zoo Wildl Med. 2016; 47: 29-37
        • Sainmaa S.
        • Mykkänen A.
        • Adam M.
        • et al.
        Intravenous vatinoxan in markhors (Capra falconeri heptneri) immobilized with intramuscular medetomidine and ketamine – a preliminary dose screening study.
        J Zoo Wildl Med. 2019; 50: 159-166
        • Seddighi R.
        • Doherty T.J.
        Field sedation and anesthesia of ruminants.
        Vet Clin North Am Food Anim Pract. 2016; 32: 553-570
        • Serrano L.
        • Lees P.
        The applied pharmacology of azaperone in ponies.
        Res Vet Sci. 1976; 20: 316-323
        • Stegman G.F.
        • Littlejohn A.
        The effect of lateral and dorsal recumbency on cardiopulmonary function in the anaesthetised horse.
        J S Afr Vet Assoc. 1987; 58: 21-27
        • Talke P.O.
        • Traber D.L.
        • Richardson C.A.
        • et al.
        The effect of α2 agonist-induced sedation and its reversal with an α2 antagonist on organ blood flow in sheep.
        Anesth Analg. 2000; 90: 1060-1066
        • Tamura J.
        • Ishizuka T.
        • Fukui S.
        • et al.
        The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs.
        J Vet Med Sci. 2015; 77: 289-296
        • Williams M.
        • Caulkett N.A.
        • Neuhaus P.
        • et al.
        Comparison of the efficacy and safety of medetomidine-ketamine versus medetomidine-azaperone-alfaxalone combination in free-ranging Rocky Mountain Bighorn sheep (Ovis canadensis).
        J Zoo Wildl Med. 2018; 49: 662-670
        • Wildsmith J.A.
        • Drummond G.B.
        • MacRae W.R.
        Blood-gas changes during induced hypotension with sodium nitroprusside.
        Br J Anaesth. 1975; 47: 1205-1211
        • Wright P.
        • Ishihara Y.
        • Bernard G.R.
        Effects of nitroprusside on lung mechanics and hemodynamics after endotoxemia in awake sheep.
        J Appl Physiol. 1985; 64: 2026-2032