A Model-Based Approach for Joint Analysis of Pain Intensity and Opioid Consumption in Postoperative Pain.

Joint analysis of pain intensity and opioid consumption is encouraged in trials of postoperative pain. However, previous approaches have not appropriately addressed the complexity of their interrelation in time. In this study, we applied a non-linear mixed effects model to simultaneously study pain intensity and opioid consumption in a 4-h postoperative period for 44 patients undergoing percutaneous kidney stone surgery. Analysis was based on 748 Numerical Rating Scale (NRS) scores of pain intensity and 51 observed morphine and oxycodone dosing events. A joint model was developed to describe the recurrent pattern of four key phases determining the development of pain intensity and opioid consumption in time; (A) Distribution of pain intensity scores which followed a truncated Poisson distribution with time-dependent mean score ranging from 0.93 to 2.45; (B) Probability of transition to threshold pain levels (NRS ≥ 3) which was strongly dependent on previous pain levels ranging from 2.8-15.2% after NRS of 0-2; (C) Probability of requesting opioid when allowed (NRS ≥ 3) which was strongly correlated with the number of previous doses, ranging from 89.8% for requesting the first dose to 26.1% after three previous doses; (D) Reduction in pain scores after opioid dosing which was significantly related to the pain intensity at time of opioid request (P < 0.001). This study highlights the importance of analyzing pain intensity and opioid consumption in an integrated manner. Non-linear mixed effects modeling proved a valuable tool for analysis of interventions that affect pain intensity, probability of rescue dosing or the effect of opioids in the postoperative pain period.

Pathophysiological aspects of ureterorenoscopic management of upper urinary tract calculi.

PURPOSE OF REVIEW: Indications for ureterorenoscopy are expanding without hard scientific evidence to support its efficacy. Therefore, it is extremely important to focus on potential harmful effects of the procedure itself. This review explores how physiology of the upper urinary tract reacts to ureterorenoscopy, potentially translating into harmful effects, and how such pathophysiological processes may be minimized. RECENT FINDINGS: Complications to ureterorenoscopy and postoperative pain seem to be related to intrarenal pressure and/or access. Mean intrarenal pressures in the range of 60-100 mmHg during ureterorenoscopy without access sheaths have been measured, thus by far exceeding the threshold for intrarenal backflow, potentially resulting in septic complications. Intrarenal pressure may be reduced by use of ureteral access sheaths, which, however, may cause ureteral damage due to the limited size of the ureter and strain-induced ureteral contractions (peristalsis). Different receptor types modulate this peristaltic activity. ß-receptor agonists have been investigated in animal and human trials for the purpose of relaxing the ureter. In randomized, placebo-controlled trials in pigs and humans, usage of the ß-receptor agonist isoproterenol in the irrigation fluid has shown a potential for reducing both intrarenal pressure and ureteral tone during ureterorenoscopy. SUMMARY: Upper urinary tract physiology has unique features that may be pushed into pathophysiological processes by the unique elements of ureterorenoscopy: access and irrigation. Pharmacological ureteral relaxation during ureterorenoscopy deserves further attention with regard to reducing complications and postoperative pain.