The influence of a fentanyl and dexmedetomidine combination on external respiratory functions in acute hemorrhage model

Background. The synthetic opioid analgesic fentanyl is widely used for prophylaxis and therapy of traumatic shock associated with massive bleeding. Its side effects – skeletal muscle rigidity and respiratory center depression – are especially pronounced with repeated administration. It is rational to apply fentanyl in diminished doses in combination with non-opioid analgesics in order to reduce respiratory disturbances risk.

Aim. The aim of the work is to justify the influence of opioid analgesic fentanyl and α2 -adrenomimetic dexmedetomidine combination on external respiratory functions in acute hemorrhage model.

Materials and methods. Acute loss of 35–40% of circulating blood volume was modeled in experiments on 75 white mongrel male rats. The external respiratory functions (respiratory rate, respiratory volume, breath volume per minute) were estimated in animals of 5 groups: 1 – rats without analgesic help (controls); 2–3 – rats receiving a single fentanyl intramuscular injection (ED99 98,96 mcg/kg) or fentanyl together with dexme detomidine (ED99 of combination 67,94 mcg/kg) 15 min after acute blood loss; 4–5 – rats receiving the same drugs 15 min, 30, 45 and 60 min later.

Results. In experimental acute loss of 35–40% of circulating blood volume, 15 min later a secondary acute respiratory failure developed with a drop of respiratory rate, respiratory volume and volume of breath per minute by 30%, 21 and 47% (p < 0,05). The external respiratory functions recoverеd after 4 h mainly due to the increase of respiratory volume. A single intramuscular injection of fentanyl caused respiratory depression 15 min after experimental blood loss which resulted in the decrease of breath volume per minute to 30–61% (p < 0,05) for 90 min. Four intramuscular injections of fentanyl 15 min, 30, 45 and 60 min after hemorrhage caused a severe respiratory dysfunction, accompanied by apnea periods and Biot’s respiration. Respiratory rate was reduced to 45–60%, breath volume per minute – to 21–44% (p < 0,05). The respiration improved after 24 h. The addition of central α2 -adrenomimetic dexmedetomidine to the analgesic therapy with fentanyl reduced respiratory depression with the decrease of breath volume to 37–62% (p < 0,05) and an earlier, after 4 h recovery.

Conclusion. The repeated injections of fentanyl in diminished dose together with dexmedetomidine in experimental acute hemorrhage caused a pronounced analgesic effect with lower than in fentanyl alone respiratory depression. 

1. Zyblev S.L., Dundarov Z.А., Gritsuk А.I. Sostoyaniye antioksidantnoy aktivnosti krovi pri gemorragicheskom shoke v eksperimente [The state of antioxidant blood activity in hemorrhagic shock in experiment] // Problemy zdorov’ya i ekologii – Problems of health and ecology. 2013; 36 (2): 93–97 (in Russian).

2. Simonenkov А.P., Fedorov V.D. O edinstve tkanevoy gipoksii i shoka [About unity of hypoxia and shock] // Аnesteziologiya i reanimatologiya – Anesthesiology and Intensive Care. 2000; 6: 73–76 (in Russian).

3. Shanin V.Yu. Patofiziologiya kriticheskikh sostoyaniy [Pathophysiology of critical conditions]. St-Petersburg: ELBI-SPb. Publ., 2003: 436 (in Russian).

4. Ehieli E., Yalamuri S., Brudney C.S., Pyati S. Analgesia in the surgical intensive care unit // Postgrad. Med. J. 2017; 93 (1095): 38–45. doi: 10.1136/postgradmedj-2016-134047.

5. Pasero C. Fentanyl for acute pain management // J. Perianesth. Nurs. 2005; 20 (4): 279–284. doi: 10.1016/j. jopan. 2005.03.007

6. Feld J.M., Hoffman W.E., Paisansathan C. et al. Autonomic activity during dexmedetomidine or fentanyl infusion with desflurane anesthesia // J. Clin. Anesth. 2007; 19 (1): 30–36. doi: 10.1016/j.jclinane.2006.05.019.

7. Uzümcügil F., Canbay O., Celebi N et al. Comparison of dexmedetomidine-propofol vs. fentanyl-propofol for laryngeal mask insertion // Eur. J. Anesthesiol. 2008; 25 (6): 675–680. doi: 10.1017/S026502150800421.

8. Rukovodstvo po provedeniyu doklinicheskikh issledovaniy lekarstvennykh sredstv [The guide for the carrying of preclinical studies of medicines]. Moscow, 2012: 944 (in Russian).

9. Zyblev S.L., Dundarov Z.А., Martem’yanova L.А. Eksperimental’naya model’ gemorragicheskogo shoka [Experimental model of hemorrhagic shock] // Problemy zdorov’ya i ekologii – Problems of health and ecology. 2013; 35 (1): 109–113 (in Russian).

10. Hoymann H.G. Invasive and noninvasive lung function measurements in rodents // J. Pharmacol. Toxicol. Methods. 2007; 55 (1): 16–26. doi:10.1016/j.vascn.2006.04.006.

11. Keating G.M. Dexmedetomidine: a review of its use for sedation in the intensive care setting // Drugs. 2015; 75 (10): 1119–1130. doi: 10.1007/s40265-015-0419-5

12. Darnobid J.A. The pharmacology of total intravenous anesthesia // Int. Anesthesiol. Clin. 2015; 53 (2): 13–27. doi: 10.1097/AIA.0000000000000057.