Morphine-Induced Blood Gas Changes

The changes in pH, pCO₂, pO₂ and sO₂ elicited by injection of morphine (10 mg/kg, IV) in 3 separate groups of freely moving rats (n = 9 rats per group) followed 15 min later by injection of vehicle (saline; 80.0 ± 0.6 days of age; 342 ± 2 g body weight), d-cystine (500 μmol/kg, IV; 79.7 ± 0.4 days; 340 ± 2 g) or d-cystine diME (500 μmol/kg, IV; 79.3 ± 0.4 days; 338 ± 2 g) were determined as detailed previously (49). Arterial blood samples (100 μL) were taken 15 min before and 15 min after injection of morphine (10 mg/kg, IV). The rats then immediately received an injection of vehicle, d-cystine or d-cystine diME and blood samples were taken 5, 15, 30 and 45 min later. The pH, pCO₂, pO₂ and sO₂ were measured using a Radiometer blood-gas analyzer (ABL800 FLEX). The A-a gradient measures difference between alveolar and arterial blood O₂ concentrations^{23 (link),31 (link),32 (link)}. A decrease in PaO₂, without a change in A-a gradient is normally accompanied by an increase in paCO₂ (as observed here) if it is caused by hypoventilation. Hypoxia is irreversible if caused by shunt. An increased A-a gradient is caused either by oxygen diffusion limitation (usually not readily reversible) or ventilation-perfusion mismatch^{23 (link),31 (link),32 (link)}. A-a gradient = PAO₂ − PaO₂, where PAO₂ is the partial pressure of alveolar O₂ and PaO₂ is pO₂ in arterial blood. PAO₂ = [(FiO₂ × (P_atm—P_H2O)—(PaCO₂/respiratory quotient)], where FiO₂ is the fraction of O₂ in inspired air; P_atm is atmospheric pressure; P_H2O is the partial pressure of H₂O in inspired air; PaCO₂ is pCO₂ in arterial blood; and respiratory quotient (RQ) is the ratio of CO₂ eliminated/O₂ consumed. We took FiO₂ of room-air to be 21% = 0.21, P_atm to be 760 mmHg, and P_H2O to be 47 mmHg^{23 (link)}. We did not determine RQ values directly, but took the resting RQ value of our adult male rats to be 0.9 on the basis of work by others^{33 (link),34 (link)}. Based on extensive evidence detailed by Mendoza et al.^{22 (link)}, we used a RQ value of 0.9 to calculate A-a gradient throughout the blood-gas protocols on the assumption that morphine and the thiolesters do not directly affect this value, although this must be directly addressed in our protocols at some point. Here, we had both alveolar hypoventilation and ventilation-mismatch. In almost all cases, when these two phenomena occur together and are readily reversed, the cause is decreased minute ventilation leading rapidly to atelectasis.