Ultiva

General anaesthesia was pre‐administered by subcutaneous injection of 0.04 mg/kg atropine sulphate (Mitsubishi Tanabe Pharma Co., Osaka, Japan), followed by intravenous injection of 0.1 mg/kg midazolam (Dormicum; Astellas Pharma Inc., Tokyo, Japan) and 0.1 ml/kg fentanyl citrate‒droperidol (Thalamonal; Daiichi‐Sankyo Propharma Co., Ltd., Tokyo, Japan). General anaesthesia was induced using propofol (Mylan; Mylan Seiyaku Ltd., Tokyo, Japan). Endotracheal intubation was subsequently performed. Each dog was mechanically ventilated with 2.0%–2.5% isoflurane (IsoFlo; Zoetis Japan, Tokyo, Japan) and oxygen. For analgesia, intra‐ and post‐operative continuous drip infusions of remifentanil (5–40 μg/kg/h) (Ultiva; Janssen Pharmaceutical K.K., Tokyo, Japan) and pre‐ and post‐operative intramuscular injections of morphine hydrochloride (0.3 mg/kg each dose) (Takeda Pharmaceutical Co. Ltd. Osaka, Japan) were used.
Prior to surgery, CT was performed, and the volume (cm³) of the lung mass was measured in terms of length, width, and height. All patients were approached through an intercostal or median sternotomy depending on the region and size of the individual tumours, and the tumours were resected by lung lobectomy. All resected masses were weighed.

Drugs were dissolved in Krebs solution and applied by perfusion via a three-way stopcock without any change in either the perfusion rate or the temperature. The drugs used in this study were Ultiva®, 2 mg (Janssen Pharmaceutical K.K., Tokyo, Japan), TTX (Wako, Osaka, Japan), glycine (Wako) and naloxone hydrochloride (Wako). All drugs were diluted to their final concentration in Krebs solution immediately before use. A 2-mg Ultiva® vial contains 15 mg glycine as an adjunct. Ultiva® containing 50 μM remifentanil hydrochloride with 2 mM glycine was superfused on to spinal cord slice preparations in vivo and ex vivo. The plasma concentration of remifentanil achieved by an intravenous infusion of Ultiva® at 0.05–0.20 μg·kg⁻¹ min⁻¹ is approximately 1–5 ng/ml [14 (link), 15 (link)]. Remifentanil has a rapid blood-brain equilibration half-time because of its rapid onset of action. Although the transit of remifentanil to the cerebrospinal fluid is not completely understood, the concentration of Ultiva® superfused was not determined from the plasma concentration, but from the effect obtained in a previous study of Ultiva® or pure remifentanil [5 (link), 16 (link)].