If it is necessary to use naloxone to reverse clinically significant respiratory depression, it should be titrated very carefully (APS, 2008). Sometimes, more than one dose of naloxone is necessary because naloxone has a shorter duration (1 hour in most patients) than most opioids; however, giving too much naloxone or giving it too fast can precipitate severe pain that is extremely difficult to control and can increase sympathetic activity leading to hypertension, tachycardia, ventricular dysrhythmias, pulmonary edema, and cardiac arrest (Brimacombe, Archdeacon, Newell, & Martin, 1991; O’Malley-Dafner & Davies, 2000). Hospital protocols and opioid orders should include the expectation that nurses will administer naloxone in accordance with the American Pain Society (2008) recommendation to dilute 0.4 mg of naloxone in 10 mL saline and administer intravenously very slowly while observing patient response (titrate to effect) whenever a patient is found to have clinically significant opioid-induced respiratory depression. In physically dependent patients, withdrawal syndrome can be precipitated by naloxone administration; patients who have been receiving opioids for more than 1 week may be exquisitely sensitive to antagonists (APS, 2008).