Evaluation of efficacy and safety of pulsed inhaled nitric oxide in the anesthetized horse : preparing for clinical use

Sammanfattning: Anesthetized, recumbent horses commonly develop hypoxemia secondary to ventilation/perfusion (VA/Q) mismatch and shunting of pulmonary blood (Qs/Qt) through atelectatic lung regions. Hypoxemia in the anesthetized horse is difficult to treat and ventilatory therapy is often ineffective. Nitric oxide (NO) can be inhaled (iNO) to provide selective dilatation of pulmonary blood vessels with no systemic effects. However, conventional continuously delivered iNO is ineffective in the anesthetized horse. Conversely, pulse-delivered iNO (PiNO) may be effective and the lower PiNO dose could reduce the risk of NO accumulation in the anesthetic circuit, alleviating adverse effects from NO accumulation. However, a rapid and profound decrease in oxygen (‘rebound effect’), potentially mediated by endothelin-1 (ET-1), can occur with abrupt cessation of iNO at the end of anesthesia and this would limit the usefulness of PiNO in the horse since recovery is a critical period. PiNO decreases VA/Q mismatch but the mechanism is unknown. The aims were to determine the 1) most effective PiNO pulse duration, 2) efficacy and safety of PiNO during prolonged inhalation anesthesia and during recovery from anesthesia, and 3) mechanism of improved pulmonary function. PiNO increased oxygen and decreased Qs/Qt in both dorsally (Paper I) and laterally (Paper II) recumbent horses for an approximate surgical duration (2.5 hours) when PiNO was delivered at the most effective pulse duration (first 30-45% of the first part of inspiration; Paper I). The efficacy continued into recovery following PiNO cessation and PaO2 was higher and Qs/Qt lower in PiNO horses than in control horses for the entire recovery period. No rebound effect occurred in horses still anesthetized or those recovering from anesthesia. ET-1 concentrations were not increased by PiNO. No residual NO was present in the breathing circuit. The mechanism of PiNO as determined by multiple inert gas elimination technique (MIGET) was improved matching of VA and Q. Using scintigraphy, the improvement was determined to be due to a movement of blood against gravity from the dependent, atelectatic regions of the lung to the non-dependent aerated portions of the lung. In conclusion, we have shown that PiNO is effective and safe in anesthetized and recovering horses.. PiNO redistributes blood flow from dependent to non-dependent regions of the lung, thereby decreasing Qs/Qt and improving VA/Q matching. We are confident that PiNO is ready for clinical use in anesthetized horses.