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HYPOXEMIA PREVENTS RECOVERY FOLLOWING FENTANYL OVERDOSE IN AWAKE AND SEDATED RATS
Author(s) -
Guck Daniel,
McCann Marissa,
Tubbs Nicole,
Haouzi Philippe
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.01859
Subject(s) - fentanyl , anesthesia , medicine , hypoxemia , apnea , (+) naloxone , ventilation (architecture) , tidal volume , arterial blood , bolus (digestion) , opioid , respiratory system , mechanical engineering , receptor , engineering
Background As severe acute hypoxemia produces a rapid inhibition of the respiratory neuronal activity through a non‐opioid mechanism, we have investigated in adult rats the effects of hypoxemia following fentanyl overdose‐induced apnea on 1‐ auto‐resuscitation and 2‐ the antidotal effects of naloxone. Methods In unsedated rats, the breath‐by‐breath ventilatory and pulmonary gas exchange response to fentanyl overdose (300 mg.kg −1 .min −1 iv in one minute) was determined in an open flow plethysmograph. The effects of inhaling air (9 rats) or a hypoxic mixture (FIO 2 between 7.3 amd 11.3%, 8 rats) on the ability to recover a spontaneous breathing rhythm and on the effects of naloxone (2 mg/kg) were investigated. In addition, arterial blood gases, arterial blood pressure, ventilation and pulmonary gas exchange were determined in spontaneously breathing tracheostomized urethane‐anesthetized rats in response to 1‐ fentanyl induced hypoventilation (7 rats), 2‐ fentanyl induced apnea (10 rats) in air and hyperoxia, and 3‐ isolated anoxic exposure (6 rats). Results Data are expressed as median and range. In the unsedated rat model, bolus fentanyl injection in air breathing produced an apnea within 14 seconds (12 – 29 seconds). A spontaneous rhythmic activity resumed after 85.4 s (33–141 seconds) consisting in a persistent low tidal volume and slow frequency rhythmic activity that rescued all animals. Naloxone at 10 minutes immediately restored the baseline level of ventilation. At FIO 2 below 10%, fentanyl induced apnea was irreversible despite a transient gasping pattern, the administration of naloxone had no effects. In sedated rats, no spontaneous recovery of breathing occurred following fentanyl‐induced apnea, when PaO 2 was lower than 16 mmHg, akin to the effects of hypoxemia alone. Naloxone had no rescuing effect on fentanyl‐induced apnea despite circulation being maintained . Conclusion Hypoxia‐induced ventilatory depression during fentanyl induced apnea 1) opposes the spontaneous emergence of a respiratory rhythm, which would have rescued the animals otherwise, 2) prevents the effects of high dose naloxone. Support or Funding Information None