Winfried Meissner

Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures.

Background:Severe pain after surgery remains a major problem, occurring in 20–40% of patients. Despite numerous published studies, the degree of pain following many types of surgery in everyday clinical practice is unknown. To improve postoperative pain therapy and develop procedure-specific, optimized pain-treatment protocols, types of surgery that may result in severe postoperative pain in everyday practice must first be identified. Methods:This study considered 115,775 patients from 578 surgical wards in 105 German hospitals. A total of 70,764 patients met the inclusion criteria. On the first postoperative day, patients were asked to rate their worst pain intensity since surgery (numeric rating scale, 0–10). All surgical procedures were assigned to 529 well-defined groups. When a group contained fewer than 20 patients, the data were excluded from analysis. Finally, 50,523 patients from 179 surgical groups were compared. Results:The 40 procedures with the highest pain scores (median numeric rating scale, 6–7) included 22 orthopedic/trauma procedures on the extremities. Patients reported high pain scores after many “minor” surgical procedures, including appendectomy, cholecystectomy, hemorrhoidectomy, and tonsillectomy, which ranked among the 25 procedures with highest pain intensities. A number of “major” abdominal surgeries resulted in comparatively low pain scores, often because of sufficient epidural analgesia. Conclusions:Several common minor- to medium-level surgical procedures, including some with laparoscopic approaches, resulted in unexpectedly high levels of postoperative pain. To reduce the number of patients suffering from severe pain, patients undergoing so-called minor surgery should be monitored more closely, and postsurgical pain treatment needs to comply with existing procedure-specific pain-treatment recommendations.

A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.

Background: Opioid‐induced constipation can have a major negative impact on patients’ quality of life. This randomised, double‐blinded study evaluated the analgesic efficacy of prolonged‐release (PR) oral oxycodone when co‐administered with PR oral naloxone, and its impact on opioid‐induced constipation in patients with severe chronic pain. Another objective was to identify the optimal dose ratio of oxycodone and naloxone.

Oral naloxone reverses opioid-associated constipation.

Abstract Opioid‐related constipation is one of the most frequent side effects of chronic pain treatment. Enteral administration of naloxone blocks opioid action at the intestinal receptor level but has low systemic bioavailability due to marked hepatic first‐pass metabolism. The aim of this study was to examine the effects of oral naloxone on opioid‐associated constipation in an intraindividually controlled manner. Twenty‐two chronic pain patients with oral opioid treatment and constipation were enrolled in this study. Constipation was defined as lack of laxation and/or necessity of laxative therapy in at least 3 out of 6 days. Laxation and laxative use were monitored for the first 6 days without intervention (‘control period’). Then, oral naloxone was started and titrated individually between 3×3 to 3×12 mg/day depending on laxation and withdrawal symptoms. After the 4‐day titration period, patients were observed for further 6 days (‘naloxone period’). The Wilcoxon signed rank test was used to compare number of days with laxation and laxative therapy in the two study periods. Of the 22 patients studied, five patients did not reach the ‘naloxone period’ due to death, operation, systemic opioid withdrawal symptoms, or therapy‐resistant vomiting. In the 6 day ‘naloxone’ compared to the ‘control period’, the mean number of days with laxation increased from 2.1 to 3.5 (P<0.01) and the number of days with laxative medication decreased from 6 to 3.8 (P<0.01). The mean naloxone dose in the ‘naloxone period’ was 17.5 mg/day. The mean pain intensity did not differ between these two periods. Moderate side effects of short duration were observed in four patients following naloxone single dose administrations between 6 and 20 mg, resulting in yawning, sweating, and shivering. Most of the patients reported mild or moderate abdominal propulsions and/or abdominal cramps shortly after naloxone administration. All side effects terminated after 0.5–6 h. This controlled study demonstrates that orally administered naloxone improves symptoms of opioid associated constipation and reduces laxative use. To prevent systemic withdrawal signs, therapy should be started with low doses and patients carefully monitored during titration.

Analgesic Efficacy and Safety of Oxycodone in Combination With Naloxone as Prolonged Release Tablets in Patients With Moderate to Severe Chronic Pain

UNLABELLED This randomized, double-blind, placebo- and active-controlled, parallel-group study was designed to demonstrate the superiority of oxycodone in combination with naloxone in a prolonged release (PR) formulation over placebo with respect to analgesic efficacy. The active control group was included for sensitivity and safety analyses, and furthermore to compare the analgesic efficacy and bowel function of oxycodone PR/naloxone PR with oxycodone PR alone. The analgesic efficacy was measured as the time from the initial dose of study medication to multiple pain events (ie, inadequate analgesia) in patients with moderate to severe chronic low back pain. The full analysis population consisted of 463 patients. The times to recurrent pain events were significantly longer in the oxycodone PR/naloxone PR group compared with placebo (P < .0001-.0003); oxycodone PR/naloxone PR reduced the risk of pain events by 42% (P < .0001; full analysis population). The appearance of pain events was comparable for oxycodone PR/naloxone PR versus oxycodone PR, confirming that the addition of naloxone PR to oxycodone PR in a combination tablet did not negatively affect analgesic efficacy of the opioid. Furthermore, oxycodone PR/naloxone PR offers benefits in terms of an improvement in bowel function. In a therapeutic area of great unmet need, therefore, the combination tablet of oxycodone PR/naloxone PR offers patients effective analgesia while improving opioid-induced bowel dysfunction. Taken together with the observation that the safety profile of oxycodone PR/naloxone PR is consistent with that expected from other opioid analgesics except opioid-induced constipation, these findings indicate that the addition of naloxone to oxycodone in a PR combination tablet offers improved tolerability. Oxycodone PR/naloxone PR is therefore a promising new treatment approach for the management of chronic pain. PERSPECTIVE This study evaluated the analgesic efficacy and safety of the combination of oxycodone PR/naloxone PR in chronic nonmalignant pain. Opioids are often reduced in dosage or even discontinued as a result of impaired bowel function, leading to insufficient pain treatment. Not only does oxycodone PR/naloxone PR demonstrate analgesic efficacy comparable with oxycodone PR, but it also improves opioid-induced bowel dysfunction, and may therefore improve the acceptability of long-term opioid treatment for chronic pain.

Enteral naloxone reduces gastric tube reflux and frequency of pneumonia in critical care patients during opioid analgesia

ObjectiveOpioid analgesia impairs gastrointestinal motility. Enteral administration of naloxone theoretically allows selective blocking of intestinal opioid receptors caused by extensive presystemic metabolism. Therefore, we studied the effect of enteral naloxone on the amount of gastric tube reflux, the frequency of pneumonia, and the time until first defecation in mechanically ventilated patients with fentanyl analgesia. DesignProspective, randomized, double-blinded study. SettingUniversity hospital intensive care unit. PatientsEighty-four mechanically ventilated, fentanyl-treated patients without gastrointestinal surgery or diseases. InterventionsPatients were assigned to receive 8 mg naloxone or placebo four times daily via a gastric tube during fentanyl administration. Measurements and Main ResultsThirty-eight patients received naloxone and 43 placebo; three patients were excluded because of protocol violation. Median gastric tube reflux volume (54 vs. 129 mL, p = .03) and frequency of pneumonia (34% vs. 56%, p = .04) were significantly lower in the naloxone group. In both groups, time until first defecation, ventilation time, and length of intensive care unit stay did not differ. There was no difference in fentanyl requirements between the naloxone and the placebo group (7 vs. 6.5 &mgr;g/kg/hr, p = .15). ConclusionsOur results provide evidence that the administration of enteral opioid antagonists in ventilated patients with opioid analgesia might be a simple—and possibly preventive—treatment of increased gastric tube reflux and reduces frequency of pneumonia.

Procedure-specific risk factor analysis for the development of severe postoperative pain.

Background: Many studies have analyzed risk factors for the development of severe postoperative pain with contradictory results. To date, the association of risk factors with postoperative pain intensity among different surgical procedures has not been studied and compared. Methods: The authors selected precisely defined surgical groups (at least 150 patients each) from prospectively collected perioperative data from 105 German hospitals (2004–2010). The association of age, sex, and preoperative chronic pain intensity with worst postoperative pain intensity was studied with multiple linear and logistic regression analyses. Pooled data of the selected surgeries were studied with random-effect analysis. Results: Thirty surgical procedures with a total number of 22,963 patients were compared. In each surgical procedure, preoperative chronic pain intensity and younger age were associated with higher postoperative pain intensity. A linear decline of postoperative pain with age was found. Females reported more severe pain in 21 of 23 surgeries. Analysis of pooled surgical groups indicated that postoperative pain decreased by 0.28 points (95% CI, 0.26 to 0.31) on the numeric rating scale (0 to 10) per decade age increase and postoperative pain increased by 0.14 points (95% CI, 0.13 to 0.15) for each higher score on the preoperative chronic pain scale. Females reported 0.29 points (95% CI, 0.22 to 0.37) higher pain intensity. Conclusions: Independent of the type and extent of surgery, preoperative chronic pain and younger age were associated with higher postoperative pain. Females consistently reported slightly higher pain scores regardless of the type of surgery. The clinical significance of this small sex difference has to be analyzed in future studies.

Rapid functional plasticity in the primary somatomotor cortex and perceptual changes after nerve block.

The mature human primary somatosensory cortex displays a striking plastic capacity to reorganize itself in response to changes in sensory input. Following the elimination of afferent return, produced by either amputation, deafferentation by dorsal rhizotomy, or nerve block, there is a well‐known but little‐understood ‘invasion’ of the deafferented region of the brain by the cortical representation zones of still‐intact portions of the brain adjacent to it. We report here that within an hour of abolishing sensation from the radial and medial three‐quarters of the hand by pharmacological blockade of the radial and median nerves, magnetic source imaging showed that the cortical representation of the little finger and the skin beneath the lower lip, whose intact cortical representation zones are adjacent to the deafferented region, had moved closer together, presumably because of their expansion across the deafferented area. A paired‐pulse transcranial magnetic stimulation procedure revealed a motor cortex disinhibition for two muscles supplied by the unaffected ulnar nerve. In addition, two notable perceptual changes were observed: increased two‐point discrimination ability near the lip and mislocalization of touch of the intact ulnar portion of the fourth finger to the neighbouring third finger whose nerve supply was blocked. We suggest that disinhibition within the somatosensory system as a functional correlate for the known enlargement of cortical representation zones might account for not only the ‘invasion’ phenomenon, but also for the observed behavioural correlates of the nerve block.

Long-term efficacy and safety of combined prolonged- release oxycodone and naloxone in the management of non-cancer chronic pain

Objective:  The aim of this study was to assess safety and efficacy of fixed combination oxycodone prolonged release (PR)/naloxone PR in terms of both analgesia and improving opioid‐induced bowel dysfunction (OIBD) and associated symptoms, such as opioid‐induced constipation (OIC), in adults with chronic non‐cancer pain.

Benchmarking as a tool of continuous quality improvement in postoperative pain management.

Background and objective: Quality of acute pain management is far from being satisfactory. These deficits are not caused by the complexity of the medical problem but by difficulties in organization and hospital structures, sand procedures. Continuous quality improvement is a recommended tool to overcome such difficulties and to increase quality in the long run. This study reports the implementation of benchmarking‐based continuous quality improvement to improve postoperative pain management at a university hospital. Methods: A specialised pain nurse interviewed patients of three surgical departments on the first day after surgery, and continuously assessed process and outcome quality parameters. A multidisciplinary team of anaesthetists, surgeons, nurses and pharmacists implemented a regular procedure of data analysing and internal benchmarking. Results and suggested improvements were fed back to the healthcare teams. Results: From 1998 to 2002, 6756 patients were assessed. Average pain on ambulation and maximal pain were 3.7 ± 2.4 and 5.0 ± 2.5 (mean ± SD) on a 11‐point numeric rating scale. Pain intensity at rest was 1.9 ± 1.8. Over time, pain intensity on ambulation decreased (P = 0.022) whereas maximal pain and pain at rest remained unchanged. There was an increase in the number of patients who received non‐opioid analgesia (P < 0.001). Conclusions: A continuous quality improvement process could be established and is now successfully used in clinical routine. Cornerstones of this project were frequent assessments of process and outcome parameters, regular benchmarking and implementation of feedback mechanisms. Changes in organization of medical management and multidisciplinary teamwork seem to be more important than medical or technical aspects.

Pharmacokinetics of intranasal alfentanil

STUDY OBJECTIVE To determine the pharmacokinetics of intranasal and intravenous (IV) administrations of alfentanil in 10 healthy volunteers. DESIGN Randomized, prospective, double-blind, placebo-controlled, cross-over trial with at least one week between the two modes of administration. SETTING Healthy volunteers at a university medical center. SUBJECTS 10 healthy, nondrug-dependent volunteers. INTERVENTIONS Alfentanil 0.54 mg was administered either intranasally [with 12 ml of sodium chloride (NaCl) 0.9% IV] or IV (with 12 sprays of NaCl 0.9% intranasally). Each subject was assigned once to the intranasal and once to the IV group. To guarantee a complete elimination of alfentanil, there was a time period of at least one week between the different modes of administration. MEASUREMENTS AND MAIN RESULTS Venous blood was sampled from a cubital vein at 3, 6, 9, 12, 15, 20, 30, 60, and 120 minutes after administration. Alfentanil plasma concentrations were determined by radioimmunoassay. Maximal plasma concentrations were 20.1 ng/ml +/- 7.3 ng/ml after 9 minutes in the intranasal group. At this measurement point, the intranasal alfentanil concentrations were 64.7% (18.7 ng/ml +/- 6.8 ng/ml) of the IV concentrations (28.9 ng/ml +/- 7.9 ng/ml). The calculated bioavailability after intranasal administration was 64.96% +/- 26.3%. CONCLUSIONS This pharmacokinetic study demonstrates a rapid rise in plasma concentrations, as well as a high bioavailability, following the intranasal administration of alfentanil.