External Validation of a Recently Developed Population Pharmacokinetic Model for Hydromorphone During Postoperative Pain Therapy.

BACKGROUND AND OBJECTIVE: We recently developed a new population pharmacokinetic model for hydromorphone in patients including age and bodyweight as covariates. The aim of the present study was to evaluate prospectively the predictive performance of this new model during postoperative pain therapy. METHODS: This was a prospective, single-blinded, randomized, single-center study with two parallel arms. Fifty patients aged 40-85 years undergoing cardiac surgery involving thoracotomy were enrolled. Hydromorphone was administered postoperatively on the intensive care unit as target controlled infusion (TCI) for patient controlled analgesia (TCI-PCA) using the new pharmacokinetic model, or as conventional patient controlled analgesia (PCA). Arterial blood samples were taken for measurement of the hydromorphone plasma concentration. The predictive performance of the pharmacokinetic model was assessed by the median performance error (MDPE), the median absolute performance error (MDAPE), wobble and divergence. For comparison, the performance indices were also determined for three older models from the literature. RESULTS: 903 plasma concentrations of 41 patients were analyzed. The mean values (95 % CI) of MDPE, MDAPE, wobble and divergence for the new pharmacokinetic model were 11.2 % (3.9 to 18.7 %), 28.5 % (23.9 to 33.0 %), 21.4 % (18.0 to 24.9 %) and -1.6 %/h (-2.3 to -0.8 %/h). When compared with older models from the literature, performance was better with less overshoot after bolus doses. CONCLUSION: The new pharmacokinetic model of hydromorphone showed a good precision and a better performance than older models. It is therefore suitable for TCI with hydromorphone during postoperative pain therapy. TRIAL REGISTRATION: EudraCT 2013-002875-16, Clinical Trials NCT02035709.

Patient-controlled Analgesia with Target-controlled Infusion of Hydromorphone in Postoperative Pain Therapy.

BACKGROUND: Patient-controlled analgesia (PCA) is a common method for postoperative pain therapy, but it is characterized by large variation of plasma concentrations. PCA with target-controlled infusion (TCI-PCA) may be an alternative. In a previous analysis, the authors developed a pharmacokinetic model for hydromorphone. In this secondary analysis, the authors investigated the feasibility and efficacy of TCI-PCA for postoperative pain therapy with hydromorphone. METHODS: Fifty adult patients undergoing cardiac surgery were enrolled in this study. Postoperatively, hydromorphone was applied intravenously during three sequential periods: (1) as TCI with plasma target concentrations of 1 to 2 ng/ml until extubation; (2) as TCI-PCA with plasma target concentrations between 0.8 and 10 ng/ml during the following 6 to 8 h; and (3) thereafter as PCA with a bolus dose of 0.2 mg until the next morning. During TCI-PCA, pain was regularly assessed using the 11-point numerical rating scale (NRS). A pharmacokinetic/pharmacodynamic model was developed using ordinal logistic regression based on measured plasma concentrations. RESULTS: Data of 43 patients aged 40 to 81 yr were analyzed. The hydromorphone dose during TCI-PCA was 0.26 mg/h (0.07 to 0.93 mg/h). The maximum plasma target concentration during TCI-PCA was 2.3 ng/ml (0.9 to 7.0 ng/ml). The NRS score under deep inspiration was less than 5 in 83% of the ratings. Nausea was present in 30%, vomiting in 9%, and respiratory insufficiency in 5% of the patients. The EC50 of hydromorphone for NRS of 4 or less was 4.1 ng/ml (0.6 to 12.8 ng/ml). CONCLUSION: TCI-PCA with hydromorphone offered satisfactory postoperative pain therapy with moderate side effects.

Complete recovery after out-of-hospital cardiac arrest with prolonged (59 min) mechanical cardiopulmonary resuscitation, mild therapeutic hypothermia and complex percutaneous coronary intervention for ST-elevation myocardial infarction.

We report on a 68 years old survivor of an out-of-hospital cardiac arrest with favorable neurological outcome following prolonged cardiopulmonary resuscitation (CPR 59 min) until return of spontaneous circulation (ROSC) due to ST-elevation myocardial infarction (STEMI). The case demonstrates the beneficial effect of an optimal rescue chain including basic life support performed by trained bystanders, short response time of the emergency medical service, uninterrupted CPR during transportation using a mechanical chest compression system (LUCAS®), in combination with optimal intensive care management of cardiogenic shock after ROSC including multivessel emergency percutaneous coronary intervention (PCI) and intravascular therapeutic hypothermia (Coolgard®-System).