Postoperative Pain Trajectories and Pain Chronification-an Empirical Typology of Pain Patients.

Background: High intensity of acute postsurgical pain is one of the strongest predictors of chronic postsurgical pain (CPSP). We investigated if different types of patients with distinct combinations of initial pain intensity and rate of pain resolution exhibit different risks for increased pain intensity six months after surgery. Methods: Data from 174 patients were examined using growth mixture analysis by means of structural equation modeling. Results: Three types of patients were distinguished on the basis of acute pain trajectories. The majority of patients (57%) showed an unproblematic pattern of little initial pain on the first postoperative day, combined with further pain resolution over the four subsequent days. There also was a substantial group of patients (30%) who started out with severe pain but exhibited a high rate of pain resolution. Finally, we found a problematic group of patients (13%) who reported high pain intensities throughout all five postoperative measurements, with no signs of pain resolution. Even after controlling for preoperative pain intensity, these patients exhibited significantly higher pain intensities six months after surgery than the remaining patient groups. Conclusions: In this study, we demonstrated that there is substantial variation in postsurgical pain trajectories, not only with regard to postsurgical initial pain intensity, but also with regard to individual rates of pain resolution. Successful pain resolution appeared to be a better predictor of absence of increased pain intensities six months after surgery than initial pain immediately after surgery. Hence, attention should be given to appropriate pain treatment in order to minimize the risk of CPSP.

Tapentadol Prolonged Release for Chronic Pain: A Review of Clinical Trials and 5 Years of Routine Clinical Practice Data.

Tapentadol prolonged release (PR) for the treatment of moderate to severe chronic pain combines 2 modes of action. These are µ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule that allow higher analgesic potency through modulation of different pharmacological targets within the pain transmitting systems. At the same time, this can also serve as a clue for modulation of different pain-generating mechanisms according to nociceptive, neuropathic, or mixed pain conditions. Tapentadol PR has now been on the market for 5 years, with over 4.6 million people treated worldwide. A panel of pain specialists convened in Germany to review the clinical program and to discuss the role of tapentadol PR in the management of chronic pain. The clinical study program demonstrated effective and generally well-tolerated treatment for up to 2 years in a broad range of chronic pain conditions, including those with neuropathic pain components. This was confirmed in routine clinical practice observations. Head-to-head studies with World Health Organization (WHO) III opioids such as oxycodone controlled release and oxycodone/naloxone PR showed at least comparable pain relief in the treatment of moderate-to-severe musculoskeletal pain. Rotation from poorly tolerated WHO III opioids to tapentadol PR provided effective pain relief and better symptom control for musculoskeletal pain compared to previous medication. Functionality, health status and quality of life also improved under tapentadol PR treatment. The gastrointestinal tolerability profile was more favorable compared to other tested WHO III opioids. Tapentadol PR has a good safety profile and no evidence of acquired tolerance from the long-term data so far collected. Overall, tapentadol PR represents an effective and generally well-tolerated alternative to "classical" opioidergic drugs.

Incidence of chronic postsurgical pain (CPSP) after general surgery.

OBJECTIVE: This study investigated the incidence and determinants of chronic postsurgical pain (CPSP) in a general surgical patient population. DESIGN: This is a prospective cross-sectional study at a university-affiliated clinic/level 1 trauma center. Patients were followed at least 1 year postoperatively. By surgical discipline, procedures were 50% orthopedic/trauma, 33% general (abdominal/visceral), and 17% vascular. SETTING: All patients admitted during one year (N = 3020) were eligible. Exclusion criteria were cognitive impairment, communication/language barrier, nonoperative treatment, and refusal to participate. A CPSP questionnaire was completed. Step-by-step analysis followed with a 2(nd) questionnaire to detect CPSP with numeric rating scale (NRS) pain intensity ≥3. Finally, individual follow-up examinations were performed. RESULTS: 911 patients responded (30.2%). 522 complained of pain intensity ≥3 on NRS (scale 0-10). The second step identified 214 patients with chronic pain (NRS ≥3, mean 29 months postoperatively). On final examination, 83 CPSP patients (14.8%) were identified. By surgical discipline, 28% were general, 15% vascular, and 57% trauma/orthopedic surgery. Most oftenly cited pain sites were joint (49.4%), incisional/scar (37.7%), and nerve pain (33.7%). By procedure, patients underwent pelvic surgery, colon surgery, laparoscopies, inguinal herniorrhaphies, arthroscopies, and hardware extractions. All patients in the "laborer" and "unemployed" categories reported chronic pain. CONCLUSION: Bias due to study design and/or heterogeneity of patients is possible, but there was a high CPSP rate after 2 years both generally and particularly in orthopedic/trauma (57%) patients. Both "major" and "minor" surgical procedures led to CPSP.

Acute coagulopathy in isolated blunt traumatic brain injury.

BACKGROUND: The role of acute coagulopathy after traumatic brain injury (TBI) on outcome has gained increasing appreciation over the recent years. This study was conducted to assess the frequency, outcome, and risk factors associated with this complication. PATIENTS AND METHODS: Using the large, multi-center population-based Trauma Registry of the German Society for Trauma Surgery (TR-DGU), we retrospectively analyzed adult patients with isolated blunt TBI (intracranial AIS(HEAD) >or= 3 and extracranial AIS scores <3) for the presence of acute post-traumatic coagulopathy upon emergency room (ER) arrival. Coagulopathy was defined as prothrombin time test (Quick's value) <70% and/or platelets < 100,000/microl. RESULTS: From a total of 3,114 eligible patients with isolated TBI, 706 (22.7%) presented with coagulopathy upon ER arrival. Coagulopathy was associated with higher rates of craniotomies (P = 0.02), of single and multiple organ failure and with less intubation-free days. In surviving patients, ICU length of stay and hospital length of stay were significantly longer, if coagulopathy had been present at admission. The overall hospital mortality was 50.4% (n = 356) in patients with coagulopathy vs. 17.3% (n = 417) in non-coagulopathic patients (all P < 0.001). Multivariate analysis identified AIS(HEAD) severity grade, GCS or=2,000 ml and age >or=75 years as independent risk factors for coagulopathy after TBI. Acute coagulopathy in TBI had an adjusted odds ratio for hospital mortality of 2.97 (CI(95): 2.30-3.85; P < 0.001). CONCLUSION: Coagulopathy upon ER admission is frequent after isolated blunt TBI and represents a powerful, independent predictor related to prognosis. Future research should aim to determine the beneficial effects of early treatment of TBI-associated coagulopathy.

Changes in transfusion practice in multiple injury between 1993 and 2006: a retrospective analysis on 5389 patients from the German Trauma Registry.

To evaluate transfusion practices in multiple injured patients and to demonstrate changes in the pattern of packed red blood cell (pRBC) transfusions over the last one-and-half decade (1993-2006). A retrospective analysis using the German Trauma Registry database (DGU-Traumaregister) including 29 353 multiple injured patients was conducted. The study population included primary admissions presenting to the emergency room (ER) with clinical and laboratory signs of active haemorrhage [haemoglobin < 9 g x dL(-1), platelets < 90000 xmicroL(-1) and prothrombin time (Quick-value) < 60%]. The pattern of pRBC transfusions was followed from ER to intensive care unit (ICU) admission. A total of 5389 patients with complete data sets were divided into the following three groups according to the year of treatment and analysed: (a) group 1: 1993-1998 (n = 870), (b) group 2: 1999-2002 (n = 2044) and (c) group 3: 2003-2006 (n = 2475). Patients had a mean age of 40.5 (+/-20) years and were predominantly male (67.2%). All patients were substantially injured (mean injury severity score = 32 +/- 15.5) and in 93% the mechanism of injury was blunt. The percentage of patients who received pRBC transfusions between ER and ICU dropped from 72% in 1993-1998 to 54% in 2003-2006 (P < 0.005). Similarly, the percentage of patients receiving mass transfusions (> 10 pRBC units) dropped from 51.3 to 17.1%. This decline was accompanied by lower incidence rates for septic complications, ventilator days, ICU length-of-stay and mortality. pRBC transfusion practices in acute trauma care have changed substantially over the last one-and-half decade and were associated with better outcome.

Is smaller necessarily better? A systematic review comparing the effects of minilaparoscopic and conventional laparoscopic cholecystectomy on patient outcomes.

BACKGROUND: In recent years, minilaparoscopic cholecystectomy (MLC; total size of trocar incision < 25 mm) has been increasingly advocated for the removal of the gallbladder, due to potentially better surgical outcomes (e.g., better cosmetic result, reduced pain, shorter hospital stay, quicker return to activity), but an evidence-based approach has been lacking. The current systematic review was undertaken to evaluate the importance of total size of trocar incision in improving surgical outcomes in adult laparoscopic cholecystectomy (LC). METHODS: The literature was systematically reviewed using MEDLINE and EmBASE. Only randomized controlled trials in English, investigating minilaparoscopic versus conventional LC (total size of trocar incision > or = 25 mm) and reporting pain scores were included. Quantitative analyses (meta-analyses) were performed on postoperative pain scores and other patient outcomes from more than one study where feasible and appropriate. Qualitative analyses consisted of assessing the number of studies showing a significant difference between the techniques. RESULTS: Thirteen trials met the inclusion criteria. There was a trend towards reduced pain with MLC compared with conventional LC, without reduction in opioid use. Patients in the MLC group had slightly reduced length of hospital stay, but there were no significant differences for return to activity. The two interventions were also similar in terms of operating times and adverse events, but MLC was associated with better cosmetic result (largely patient rated). There was a significantly greater likelihood of conversion to conventional LC or to open cholecystectomy in the MLC group than there was of conversion to open cholecystectomy in the conventional LC group [OR 4.71 (95% confidence interval 2.67-8.31), p < 0.00001]. CONCLUSIONS: The data included in this review suggest that reducing the size of trocar incision results in some limited improvements in surgical outcomes after LC. However, it carries a higher risk of conversion to conventional LC or open cholecystectomy.

A systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia.

BACKGROUND: Thoracotomy induces severe postoperative pain and impairment of pulmonary function, and therefore regional analgesia has been intensively studied in this procedure. Thoracic epidural analgesia is commonly considered the "gold standard" in this setting; however, evaluation of the evidence is needed to assess the comparative benefits of alternative techniques, guide clinical practice and identify areas requiring further research. METHODS: In this systematic review of randomized trials we evaluated thoracic epidural, paravertebral, intrathecal, intercostal, and interpleural analgesic techniques, compared to each other and to systemic opioid analgesia, in adult thoracotomy. Postoperative pain, analgesic use, and complications were analyzed. RESULTS: Continuous paravertebral block was as effective as thoracic epidural analgesia with local anesthetic (LA) but was associated with a reduced incidence of hypotension. Paravertebral block reduced the incidence of pulmonary complications compared with systemic analgesia, whereas thoracic epidural analgesia did not. Thoracic epidural analgesia was superior to intrathecal and intercostal techniques, although these were superior to systemic analgesia; interpleural analgesia was inadequate. CONCLUSIONS: Either thoracic epidural analgesia with LA plus opioid or continuous paravertebral block with LA can be recommended. Where these techniques are not possible, or are contraindicated, intrathecal opioid or intercostal nerve block are recommended despite insufficient duration of analgesia, which requires the use of supplementary systemic analgesia. Quantitative meta-analyses were limited by heterogeneity in study design, and subject numbers were small. Further well designed studies are required to investigate the optimum components of the epidural solution and to rigorously evaluate the risks/benefits of continuous infusion paravertebral and intercostal techniques compared with thoracic epidural analgesia.

Embryonic stem cell transplantation after experimental traumatic brain injury dramatically improves neurological outcome, but may cause tumors.

Transplantation of embryonic stem (ES) cells may provide cures for the damaged nervous system. Pre-differentiated ES or neuronal precursor cells have been investigated in various animal models of neurodegenerative diseases including traumatic brain injury (TBI). To our knowledge, no study has yet examined the effects of undifferentiated, murine ES cells on functional recovery and tumorigenity following implantation into injured rat brains. We evaluated the effect of transplantation of undifferentiated, murine embryonic cells on the recovery of motor function following lateral fluid percussion brain injury in Sprague-Dawley rats. At 3 days post-injury, animals received stereotactic injections of either embryonic stem cell suspension or injections of phosphate buffered saline without cells (control) into the injured cortex. Neurological motor function assessments were performed before injury, 72 h, 1, 3, and 6 weeks after transplantation using a Rotatrod and a Composite Neuroscore test. During this time period brain injured animals receiving ES cell transplantation showed a significant improvement in the Rotarod Test and in the Composite Neuroscore Test as compared to phosphate buffered saline (PBS)-treated animals. At 1 week post-transplantation, ES cells were detectable in 100% of transplanted animals. At 7 weeks following transplantation, EScells were detectable in only one animal. Two of 10 xenotransplanted animals revealed tumor formation over the observation period. These findings provide evidence for therapeutic potency of embryonic stem cell transplantation after TBI in rat, but also raise serious safety concerns about the use of such cells in human.

One year ago not business as usual: wound management, infection and psychoemotional control during tertiary medical care following the 2004 Tsunami disaster in southeast Asia.

INTRODUCTION: Following the 2004 tsunami disaster in southeast Asia severely injured tourists were repatriated via airlift to Germany. One cohort was triaged to the Cologne-Merheim Medical Center (Germany) for further medical care. We report on the tertiary medical care provided to this cohort of patients. METHODS: This study is an observational report on complex wound management, infection and psychoemotional control associated with the 2004 Tsunami disaster. The setting was an adult intensive care unit (ICU) of a level I trauma center and subjects included severely injured tsunami victims repatriated from the disaster area (19 to 68 years old; 10 females and 7 males with unknown co-morbidities). RESULTS: Multiple large flap lacerations (2 x 3 to 60 x 60 cm) at various body sites were characteristic. Lower extremities were mostly affected (88%), followed by upper extremities (29%), and head (18%). Two-thirds of patients presented with combined injuries to the thorax or fractures. Near-drowning involved the aspiration of immersion fluids, marine and soil debris into the respiratory tract and all patients displayed signs of pneumonitis and pneumonia upon arrival. Three patients presented with severe sinusitis. Microbiology identified a variety of common but also uncommon isolates that were often multi-resistant. Wound management included aggressive debridement together with vacuum-assisted closure in the interim between initial wound surgery and secondary closure. All patients received empiric anti-infective therapy using quinolones and clindamycin, later adapted to incoming results from microbiology and resistance patterns. This approach was effective in all but one patient who died due to severe fungal sepsis. All patients displayed severe signs of post-traumatic stress response. CONCLUSION: Individuals evacuated to our facility sustained traumatic injuries to head, chest, and limbs that were often contaminated with highly resistant bacteria. Transferred patients from disaster areas should be isolated until their microbial flora is identified as they may introduce new pathogens into an ICU. Successful wound management, including aggressive debridement combined with vacuum-assisted closure was effective. Initial anti-infective therapy using quinolones combined with clindamycin was a good first-line choice. Psychoemotional intervention alleviated severe post-traumatic stress response. For optimum treatment and care a multidisciplinary approach is mandatory.

Functional treatment and early weightbearing after an ankle fracture: a prospective study.

OBJECTIVE: Postoperative care for ankle fractures is generally 1 of 2 regimens: 1) functional treatment combined with early weightbearing (EWB), or 2) immobilization in a cast/orthosis for 6 weeks without weightbearing (6WC). The objective of this study was 2-fold: 1) to follow a prospective group treated with EWB as to long-term subjective and objective outcomes, and 2) to compare a subset of this group with a matched group of historic controls treated with 6WC. DESIGN: Prospective, clinical, cohort observation, and retrospective matched pair analysis. SETTING: University hospital, level 1 trauma center. PATIENTS: Forty-three patients (20 males; mean age, 49 +/- 14 years) with operated Weber B/C fractures underwent EWB. For comparison, 23 patients of this group were matched to a same number of historic controls with respect to age, gender, body mass index, and fracture type. INTERVENTION: Open reduction and internal fixation (ORIF) using a 1/3-tubular-fibula-plate for the fibula, and malleolar screws for the medial malleolus fracture (in cases with a bimalleolar ankle fracture) followed by EWB or 6WC. MAIN OUTCOME MEASUREMENTS: Olerud and Tegner scores at follow-up (at least 12 months after surgery), time to full weightbearing, return to work, pain intensity (numerical rating scale (NRS)), and hospital stay. Statistical comparisons were performed by using the Mann-Whitney U test or Fisher exact test (P < 0.05). RESULTS: Patients with EWB were full weightbearing at 7 +/- 3 weeks and returned to work at 8 +/- 5 weeks after surgery. At follow-up (mean, 20 +/- 11 months after surgery), all EWB patients showed good results in the Olerud score (90 +/- 13 points). Matched-pair analysis in 23 patients in each group revealed differences between EWB and 6WC groups for hospital stay (mean, 10.8 +/- 4.7 vs. 13.6 +/- 6 days; P = 0.12), time to full weightbearing (mean, 7.7 +/- 3.1 vs. 13.5 +/- 9.4 weeks; P = 0.01), and time until return to work (mean 9.2 +/- 5.5 vs. 10.8 +/- 7 weeks; P = 0.63). No differences concerning pain intensities were observed (EWB vs. 6WC: NRS = 1.9 vs. 1.7; P = 0.12). At follow-up, Olerud scores were generally considered good for both groups; however, mean values in EWB patients were slightly higher (87 +/- 14 vs. 79 +/- 19 points; P = 0.25). In both groups, the majority of patients reached their preinjury level of activity as demonstrated by Tegner scores. CONCLUSIONS: EWB patients tolerated earlier full weightbearing compared with 6WC patients, and there were no disadvantages with EWB compared with 6WC concerning hospital stay, pain intensities, time until return to work, and Olerud/Tegner Scores. Potential candidates for EWB are patients with a stable osteosynthesis of their fractured ankles as judged by the responsible surgeon, compliance, and high motivation.

External factors and the incidence of severe trauma: time, date, season and moon.

BACKGROUND: To detect whether external factors (time of day, day of week, month and season, lunar phases) influence incidence and outcome of severely injured trauma patients. PATIENTS AND METHODS: A retrospective cohort analysis of the TraumaRegister DGU(®) (TR-DGU) was carried out over a period of 10 years (January 2002-December 2011). Data of 35,432 primary admitted patients from Germany with a severe trauma (Injury Severity Score (ISS) >15) were analysed in this study. For the outcome evaluation transferred patients were excluded as well as those who did not have a valid Revised Injury Severity Classification (RISC) prognostic score. The outcome analysis could be performed in 31,596 (89.2%) patients. Incidence, demographics and injury pattern were analysed. For outcome analysis the observed hospital mortality was compared with the expected prognosis. RESULTS: Time of day was the factor that showed the highest variation in trauma incidence due to rush hours. Saturday was the day with the highest accident rate. Most accidents in the night happened on weekends. June and July were the months with the highest trauma rate with a large portion of two-wheel drivers. The days of year with the lowest trauma incidence rate were those between Christmas and New Year, and the highest rate was observed on May 1st. The outcome of the trauma patients was close to the prognosis in all investigated subgroups. CONCLUSION: There are clear differences in incidence but not in outcome of the patients due to external factors.

Venous thromboembolism after severe trauma: incidence, risk factors and outcome.

BACKGROUND: Venous thromboembolic events (VTEs) are common life-threatening complications after trauma, but epidemiology and reported risk factors still vary. The purpose of this investigation was to determine the incidence of VTEs among hospitalised trauma patients, to identify potential risk factors and to assess whether their presence was associated with: (a) the magnitude and pattern of injury, (b) therapeutic interventions and (c) outcome, all by using a large population-based registry. PATIENTS AND METHODS: Patient data from the Trauma Registry of the German Society for Trauma Surgery (TR-DGU) including datasets from more than 35,000 trauma patients were screened for all clinically relevant VTEs, i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE). A total of 7937 patients were identified for further investigation and multivariate logistic regression analyses were performed to assess potential risk factors for VTEs and to evaluate the effect of VTEs on outcome. RESULTS: One hundred forty-six of 7937 patients developed clinically relevant VTEs during post-traumatic hospitalisation corresponding to an overall incidence rate of 1.8%. Two-thirds (97/146) of all VTEs occurred during the first 3 weeks after admission. At the time point of the event 118/146 (80.8%) patients were under either mechanical or chemical prophylaxis. Multivariate analysis with VTE as dependent variable identified injury severity score, the number of operative procedures, pelvic injury (abbreviated injury scale > or = 2) and concomitant diseases (i.e. diabetes, renal failure, malignancies and congenital or acquired coagulation disorders) as independent risk factors. The presence of VTEs was associated with higher frequencies of sepsis (25% vs. 9.1%), single (63.6% vs. 41.3%) and multiple organ failure (49% vs. 25%) and prolonged in-hospital length of stay (52+/-34 days vs. 29+/-30 days; all p<0.001). The mortality in the VTE group totaled 13.7% vs. 7.4% in the non-VTE group (p=0.004). The presence of PE was associated with a mortality rate of 25.7%. The adjusted odds ratio of post-traumatic VTEs for hospital mortality was 2.08 (CI95 1.15-3.78; p=0.016). CONCLUSION: The occurrence of clinically apparent VTEs during post-traumatic hospitalisation is low but associated with increased morbidity and mortality. Conclusions about the effectiveness of different thromboprophylactic measures could not be drawn, since detailed information was not recorded. However, 80.8% of VTE patients had received thromboprophylaxis at the time point of the event.

Psychosocial predictors and correlates for chronic post-surgical pain (CPSP) - a systematic review.

Chronic post-surgical pain (CPSP) is a serious problem. Incidence as high as 50% has been reported, depending on type of surgery undergone. Because the etiology of chronic pain is grounded in the bio-psychosocial model, physical, psychological, and social factors are implicated in the development of CPSP. Biomedical factors such as pre-operative pain, severe acute post-operative pain, modes of anesthesia, and surgical approaches have been extensively examined, therefore this systematic review focuses on psychosocial elements. A systematic search was performed using the PubMed, PsychINFO, Embase, and Cochrane Databases. Fifty relevant publications were selected from this search, in which psychosocial predictors for and correlates to CPSP were identified. The level of evidence was assessed for each study, and corresponding score points were awarded for ease of comparison. The grade of association with CPSP for each predictor/correlate was then determined. Depression, psychological vulnerability, stress, and late return to work showed likely correlation with CPSP (grade of association=1). Other factors were determined to have either unlikely (grade of association=3) or inconclusive (grade of association=2) correlations. In addition, results were examined in light of the type of surgery undergone. This review is intended as a first step to develop an instrument for identifying patients at high risk for CPSP, to optimize clinical pain management.

Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients.

BACKGROUND: There is increasing evidence for acute traumatic coagulopathy occurring prior to emergency room (ER) admission but detailed information is lacking. PATIENTS AND METHODS: A retrospective analysis using the German Trauma Registry database including 17,200 multiple injured patients was conducted to determine (a) to what extent clinically relevant coagulopathy has already been established upon ER admission, and whether its presence was associated (b) with the amount of intravenous fluids (i.v.) administered pre-clinically, (c) with the magnitude of injury, and (d) with impaired outcome and mortality. Eight thousand seven hundred and twenty-four patients with complete data sets were screened. RESULTS: Coagulopathy upon ER admission as defined by prothrombin time test (Quick's value) <70% and/or platelets <100,000 microl(-1), was present in 34.2% of all patients. There was an increasing incidence for coagulopathy with increasing amounts of i.v. fluids administered pre-clinically. Coagulopathy was observed in >40% of patients with >2000 ml, in >50% with >3000 ml, and in >70% with >4000 ml administered. Ten percentage of patients presented with clotting disorders although pre-clinical resuscitation was limited to 500 ml of i.v. fluids maximum. The mean ISS score in the coagulopathy group was 30 (S.D. 15) versus 21 (S.D. 12) (p<0.001). Twenty-nine percentage of patients with coagulopathy developed multi organ failure (p<0.001). Early in-hospital mortality (<24h) was 13% in patients with coagulopathy (p<0.001) and overall in-hospital mortality totalled 28% (p<0.001). CONCLUSION: There is a high frequency of established coagulopathy in multiple injury upon ER admission. The presence of early traumatic coagulopathy was associated with the amount of intravenous fluids administered pre-clinically, magnitude of injury, and impaired outcome.