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Cardiorespiratory Responses to Severe Arterial Hypoxemia with Increasing Remifentanil Plasma Concentrations in the Rabbit
Author(s) -
Quail Anthony W,
Cottee David BF,
Johnstone Janice M,
O'Hara Kate,
White Saxon W
Publication year - 2017
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.31.1_supplement.700.6
Subject(s) - remifentanil , anesthesia , medicine , arterial blood , heart rate , cardiorespiratory fitness , respiratory rate , blood pressure , propofol
Remifentanil is an ultra‐short acting synthetic opiate employed clinically as an infusion for total intravenous anesthesia, sedation and analgesia. We have previously reported that vagal control of heart rate (HR) with remifentanil during severe arterial hypoxia (PaO2 < 35 mm Hg) is maintained, while its effects on control of minute ventilation (VE), tidal volume (VT) and respiratory frequency (f) are selective (Quail et al., 2016). Although opiates can act at the carotid body (McQueen and Ribeiro 1980; Mayer, et al., 1989) and the NTS (Zhang et al. 2011), our data suggest the actions of remifentanil on cardiorespiratory control during hypoxia are mainly in the CNS, rather than at the carotid body. We now report additional data concerning the plasma concentrations of remifentanil corresponding to each dose of the drug producing these effects. An ear artery and vein of NZ White rabbits (n=6) were cannulated (lidocaine 1%). Measurements of VE, VT, f, HR, mean arterial pressure (MAP) and oxygen saturation (ear SpO2) were made during normoxia, followed by 5 minutes of hypoxia (FiO2 7–8%). After a one hour recovery, rabbits breathed air during an intravenous remifentanil infusion and the hypoxia was repeated. Arterial blood samples were taken for blood gas analysis and measurement of plasma concentrations of remifentanil (HPLC and mass spectrometry). Two doses of remifentanil were studied on each of two days, one week apart. Data were analysed using repeated measures ANOVA. In rabbits breathing air remifentanil mean plasma concentrations after 12 minutes of infusion (0.1, 0.2, 0.3, or 0.4 mcg/kg/min) were respectively 1.3, 3.1, 4.5 and 11.7 ng/ml. Remifentanil caused dose‐related falls in f, VE and HR (P<0.01), while VT and MAP were unchanged. Remifentanil concentrations during hypoxia were similar to normoxia and the reflex bradycardia observed in conscious rabbits was maintained at the lower concentrations (P<0.05). The VT response remained intact but the increase in VE was attenuated with f increasing from a lowered baseline. We conclude that at similar target plasma concentrations to those employed clinically, vagal control of heart rate with remifentanil during severe hypoxia is maintained, while the components of ventilation are selectively modified. Support or Funding Information John Hunter Charitable Research Trust and Hunter Medical Research Institute