Albert J. M. van Wijck

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.

The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial

BACKGROUND Postherpetic neuralgia is the most frequent complication of herpes zoster. Treatment of this neuropathic pain syndrome is difficult and often disappointing. We assessed the effectiveness of a single epidural injection of steroids and local anaesthetics for prevention of postherpetic neuralgia in older patients with herpes zoster. METHODS We randomly assigned 598 patients older than 50 years, with acute herpes zoster (rash <7 days) below dermatome C6, to receive either standard therapy (oral antivirals and analgesics) or standard therapy with one additional epidural injection of 80 mg methylprednisolone acetate and 10 mg bupivacaine. The primary endpoint was the proportion of patients with zoster-associated pain 1 month after inclusion. Analyses were by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN32866390. FINDINGS At 1 month, 137 (48%) patients in the epidural group reported pain compared with 164 (58%) in the control group (relative risk [RR] 0.83, 95% CI 0.71-0.97, p=0.02). After 3 months these values were 58 (21%) and 63 (24%) respectively (0.89, 0.65-1.21, p=0.47) and, at 6 months, 39 (15%) and 44 (17%; 0.85, 0.57-1.13, p=0.43). We detected no subgroups in which the relative risk for pain 1 month after inclusion substantially differed from the overall estimate. No patient had major adverse events related to epidural injection. INTERPRETATION A single epidural injection of steroids and local anaesthetics in the acute phase of herpes zoster has a modest effect in reducing zoster-associated pain for 1 month. This treatment is not effective for prevention of long-term postherpetic neuralgia.

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.

Predicting postherpetic neuralgia in elderly primary care patients with herpes zoster: prospective prognostic study.

Abstract Postherpetic neuralgia (PHN) is the most frequent complication of herpes zoster (HZ) and difficult to treat. Timely identification of high‐risk HZ‐patients enables physicians to focus on PHN prevention. To assess which simple to measure factors are independent predictors of PHN, and whether psychosocial and serological/virological parameters have additional predictive value, a prospective cohort study in primary care was conducted. We included 598 elderly (>50 years) consecutive patients with acute HZ (rash <7 days) below sixth cervical dermatome. At baseline demographic, clinical (e.g., duration and severity of pain and rash), psychological (Pain Cognition List [PCL] and Spielberger’s Anxiety Inventory), serological (VZV‐antibodies) and virological (viremia presence) variables were measured. Blood tests were performed in a random subset of 218 patients. Primary outcome was significant pain (VAS >30 on 0–100 scale) after three months. The final prediction model obtained from multivariable logistic regression was (internally) validated using bootstrapping techniques, and adjusted for optimism. Forty‐six (7.7%) patients developed PHN. Independent predictors were age (odds ratio [OR] = 1.08 per year), acute pain severity (OR = 1.02 per unit), presence of severe rash (OR = 2.31), and rash duration before consultation (OR = 0.78 per day): area under receiver‐operating‐characteristic curve [ROC area] = 0.77 (95% CI: 0.71–0.82). Of the five PCL scores, only factor V (‘trust in healthcare’) was an additional predictor (OR = 1.01 per unit), though it increased the ROC area with only 0.01 to 0.78. The Spielberger’s anxiety scores and serological and virological variables were no additional predictors. Thus, four simple variables can help physicians to timely identify elderly HZ‐patients at risk of PHN.

Memory functions in chronic pain: examining contributions of attention and age to test performance

ObjectivesPrevious studies have revealed that memory performance is diminished in chronic pain patients. Few studies, however, have assessed multiple components of memory in a single sample. It is currently also unknown whether attentional problems, which are commonly observed in chronic pain, mediate the decline in memory. Finally, previous studies have focused on middle-aged adults, and a possible detrimental effect of aging on memory performance in chronic pain patients has been commonly disregarded. This study, therefore, aimed at describing the pattern of semantic, working, and visual and verbal episodic memory performance in participants with chronic pain, while testing for possible contributions of attention and age to task performance. MethodsThirty-four participants with chronic pain and 32 pain-free participants completed tests of episodic, semantic, and working memory to assess memory performance and a test of attention. ResultsParticipants with chronic pain performed worse on tests of working memory and verbal episodic memory. A decline in attention explained some, but not all, group differences in memory performance. Finally, no additional effect of age on the diminished task performance in participants with chronic pain was observed. DiscussionTaken together, the results indicate that chronic pain significantly affects memory performance. Part of this effect may be caused by underlying attentional dysfunction, although this could not fully explain the observed memory decline. An increase in age in combination with the presence of chronic pain did not additionally affect memory performance.

Management of herpes zoster and post-herpetic neuralgia now and in the future.

Herpes zoster (HZ; shingles)--a reactivation of the latent varicella zoster virus (VZV)--can cause significant morbidity. Its major complication is pain, particularly post-herpetic neuralgia (PHN). We will review the current management strategies available for the treatment of both acute HZ and PHN, including antiviral drugs, analgesic agents, anticonvulsants, tricyclic antidepressants and topical therapies. New molecules in development that show improved activity against VZV are also covered, and new drug targets are outlined. The role of translational neuroscience in moving towards a goal of finding disease-modifying treatments will be examined.

Interventions to prevent postherpetic neuralgia: cutaneous and percutaneous techniques

Herpes zoster (HZ) or shingles is a common disease, with a reported incidence varying from 2.2 to 3.4 per 1000 persons/year (Donahue et al., 1995). For most patients skin healing and pain resolution occur within 3–4 weeks. Pain can, however, continue after the rash has healed. This condition, referred to as postherpetic neuralgia (PHN), may last for several months to years. Depending on the applied definition, 9–34% of all HZ patients develop PHN (Dworkin and Portenoy, 1996). The most important risk factors for this pain syndrome include age and the severity of acute pain and inflammation during HZ (Whitley et al., 1999). PHN has a high impact on the quality of life: many patients develop severe physical, occupational, and social disabilities as a result of the unceasing pain (Dworkin and Portenoy, 1996). Since PHN commonly occurs in the elderly, its incidence is expected to increase in our aging society. Because treatment of PHN has been disappointing, much attention is currently being given to the evaluation of interventions administered to HZ patients to prevent PHN. Several systematic reviews have addressed pharmacotherapeutic prevention of PHN (Alper and Lewis, 2000; Jackson et al., 1997; Lancaster et al., 1995; Wood et al., 1996). Their conclusions, however, are controversial, because of various methodological issues of the included studies (e.g. differences in designs used, subgroups assessed, and selected endpoints). In general, the reviews support short-term benefit of antiviral drugs, but note limited evidence for a reduction in the incidence of PHN. Famciclovir and valaciclovir, however, were shown to reduce the duration of PHN. Oral steroids reduced the severity of acute HZ pain, but had no effect on the incidence, severity, or duration of PHN. Only one small study showed that early treatment of HZ patients with the antidepressant amitriptyline caused a reduction in PHN occurrence (Bowsher, 1997). Interventions such as infiltration with local anesthetics and sympathetic and epidural blocks have also been proposed and applied to reduce the risk of PHN development. In this paper we briefly outline the current hypotheses of PHN pathophysiology as well as the possible modes of action of these interventions, and critically review the available studies that have evaluated different, cutaneous and percutaneous, techniques aimed at preventing PHN.

Clinical Diagnosis of Herpes Zoster in Family Practice

PURPOSE Family physicians usually diagnose herpes zoster on clinical grounds only, possibly resulting in false-positive diagnoses and unnecessary treatment. We wanted to determine the positive predictive value of the physicians’ judgment in diagnosing herpes zoster and to assess the applicability of dried blood spot analysis for diagnosis of herpes zoster in family practice. METHODS Our study population consisted of 272 patients older than 50 years with herpes zoster (rash for less than 7 days). Dried blood spot samples were collected from all patients and sent by mail to the laboratory. Baseline measurements included clinical signs (localization, severity, and duration of rash) and symptoms (duration and severity of pain). Varicella-zoster virus antibodies were determined at baseline and 5 to 10 days later. Multivariate logistic regression was used to assess independent associations between clinical variables and serological confirmation of herpes zoster. RESULTS Dried blood spot analysis was possible in 260 patients (96%). In 236 the diagnosis of herpes zoster was confirmed serologically (positive predictive value of clinical judgment 90.8%; 95% confidence interval, 87.3%–94.3%). Independent clinical variables for serologically confirmed herpes zoster were severity and duration of rash at first examination. CONCLUSION Family physicians have good clinical judgment when diagnosing herpes zoster in older patients. Dried blood spot analysis is a logistically convenient method for serological investigation of patients in family practice, but it is rarely needed for diagnosing herpes zoster.

Safety assessment and pharmacokinetics of intrathecal methylprednisolone acetate in dogs.

Background: Intrathecal methylprednisolone acetate (MPA) has been used in patients with chronic pain syndromes. Its safety has been debated after reports of adverse events. No systematic preclinical evaluation of MPA has been reported. In the current study, the acute and long-term effects of intrathecal MPA on dog spinal tissue was studied with the injectate reformulated to include minimal adjuvants. Methods: Seventeen dogs were implanted with intrathecal catheters and randomized to three groups: vehicle (lidocaine; 4 dogs), MPA 20 mg/ml (human dose; 7 dogs), and MPA 80 mg/ml (maximum deliverable dose; 6 dogs). In parallel with the human protocols, dogs received four injections at 7-day intervals. Clinical observations and plasma methylprednisolone measurements were done before and at intervals after intrathecal delivery. One week (acute) or 6 weeks (long-term) after the last injection, animals were sacrificed and spinal tissues harvested for histopathology. Results: Other than a brief motor block, no adverse clinical event occurred in any animal. Group A (vehicle) showed minimal histologic changes (median histology-score; acute: 1.3, long-term: 1.0). Group B (MPA 20 mg/ml) had a diffuse inflammatory reaction (acute: 2.0, long-term: 3.0), group C (MPA 80 mg/ml) a severe inflammatory response, with large inflammatory masses (acute: 4.0, long-term: 7.0) The severity of the inflammatory reaction increased significantly with increasing dose at long-term sacrifice (acute P = 0.167, long-term P = 0.014). No neuronal injury, demyelination, or gliosis was seen in any animal. Conclusion: These results, showing dose-dependent intrathecal inflammatory reactions at MPA doses and injectate concentrations comparable to those used in humans, indicate that the continued use of this modality in humans is not recommended.

Acute and subchronic effects of amitriptyline 25mg on actual driving in chronic neuropathic pain patients

The acute and subchronic effects of low doses nocturnally administered amitriptyline were compared to placebo in a double-blind crossover randomized study on driving ability and driving-related skills involving seven chronic neuropathic pain patients. Performance testing occurred at the first and last day of each 15-day drug administration period, which was preceded by a 6-day washout phase. A standardized method of measuring driving ability, the on-the-road driving test, was performed on all visits. Patients were instructed to drive with a steady lateral position while maintaining a constant speed of 95km/h. The primary outcome of the driving test is the Standard Deviation of Lateral Position (SDLP, cm), which is an index of weaving of the car. At the first treatment day, driving performance was significantly impaired in patients after nocturnal administration of 25mg amitriptyline compared to placebo. The increase in SDLP of 3cm was higher than the increment generally observed with a blood alcohol concentration of 0.5mg/ml or higher, the legal limit for driving in many countries. Also, reaction times on a memory test were significantly increased, indicating worse performance after acute treatment of amitriptyline compared to placebo. In contrast, after 2 weeks of treatment, no significant differences were found between amitriptyline and placebo, suggesting that tolerance had developed to the impairing effects of amitriptyline.