Daniel M. Pöpping

Protective Effects of Epidural Analgesia on Pulmonary Complications After Abdominal and Thoracic Surgery: A Meta-Analysis

OBJECTIVE To review the impact of epidural vs systemic analgesia on postoperative pulmonary complications. DATA SOURCES Search of databases (1966 to March 2006) and bibliographies. STUDY SELECTION Inclusion criteria were randomized comparison of epidural vs systemic analgesia lasting 24 hours or longer postoperatively and reporting of pulmonary complications, lung function, or gas exchange. Fifty-eight trials (5904 patients) were included. DATA EXTRACTION Articles were reviewed and data extracted. Data were combined using fixed-effect and random-effects models. DATA SYNTHESIS The odds of pneumonia were decreased with epidural analgesia (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.43-0.68), independent of site of surgery or catheter insertion, duration of analgesia, or regimen. The effect was weaker in trials that used patient-controlled analgesia in controls (OR, 0.64; 95% CI, 0.49-0.83) compared with trials that did not (OR, 0.30; 95% CI, 0.18-0.49) and in larger studies (OR, 0.62; 95% CI, 0.47-0.81) compared with smaller studies (OR, 0.37; 95% CI, 0.23-0.58). From 1971-2006, the incidence of pneumonia with epidural analgesia remained about 8% but decreased from 34% to 12% with systemic analgesia (P < .001); consequently, the relative benefit of epidural analgesia decreased also. Epidural analgesia reduced the need for prolonged ventilation or reintubation, improved lung function and blood oxygenation, and increased the risk of hypotension, urinary retention, and pruritus. Technical failures occurred in 7%. CONCLUSION Epidural analgesia protects against pneumonia following abdominal or thoracic surgery, although this beneficial effect has lessened over the last 35 years because of a decrease in the baseline risk.

Effectiveness and safety of postoperative pain management: a survey of 18 925 consecutive patients between 1998 and 2006 (2nd revision): a database analysis of prospectively raised data†

BACKGROUND Approximately 30-80% of postoperative patients complain about moderate to severe post-surgical pain, indicating that postoperative pain treatment is still a problem. METHODS We analysed prospectively collected data on patients in a university hospital receiving systemic and epidural patient-controlled analgesia and continuous peripheral nerve block (CPNB) documented by the acute pain service team in a computer-based system. RESULTS Of 18 925 patients visited in the postoperative period between 1998 and 2006, 14 223 patients received patient-controlled epidural analgesia (PCEA), 1591 i.v. patient-controlled analgesia (IV-PCA), 1737 continuous brachial plexus block, and 1374 continuous femoral/sciatic nerve block. Mean dynamic and resting pain scores (VAS 0-100) were significantly lower for peripheral or neuroaxial regional analgesia compared with patient-controlled systemic opioid analgesia (P<0.05). The risk of a symptomatic spinal mass lesion including epidural haematoma (0.02%; 1:4741) or epidural abscess (0.014%; 1:7142) after PCEA was 1:2857 (0.04%). Neurological complications after CPNB occurred in two patients who received interscalene brachial plexus block. CONCLUSIONS We demonstrated that PCEA, IV-PCA, and CPNB are safe and efficient. Although all of these treatment strategies provide effective analgesia, PCEA and CPNB provided superior pain relief compared with IV-PCA. We demonstrated that serious complications of analgesic techniques are rare but possibly disastrous necessitating a close supervision by an acute pain service. We found a low rate of adverse effects including hypotension and motor impairment and a low incidence of epidural haematoma for thoracic PCEA compared with lumbar PCEA.

Impact of Epidural Analgesia on Mortality and Morbidity After Surgery Systematic Review and Meta-analysis of Randomized Controlled Trials

Objective:To quantify benefit and harm of epidural analgesia, compared with systemic opioid analgesia, in adults having surgery under general anesthesia. Background:It remains controversial whether adding epidural analgesia to general anesthesia decreases postoperative morbidity and mortality. Methods:We searched CENTRAL, EMBASE, PubMed, CINAHL, and BIOSIS till July 2012. We included randomized controlled trials comparing epidural analgesia (with local anesthetics, lasting for ≥24 hours postoperatively) with systemic analgesia in adults having surgery under general anesthesia, and reporting on mortality or any morbidity endpoint. Results:A total of 125 trials (9044 patients, 4525 received epidural analgesia) were eligible. In 10 trials (2201 patients; 87 deaths), reporting on mortality as a primary or secondary endpoint, the risk of death was decreased with epidural analgesia (3.1% vs 4.9%; odds ratio, 0.60; 95% confidence interval, 0.39–0.93). Epidural analgesia significantly decreased the risk of atrial fibrillation, supraventricular tachycardia, deep vein thrombosis, respiratory depression, atelectasis, pneumonia, ileus, and postoperative nausea and vomiting, and also improved recovery of bowel function, but significantly increased the risk of arterial hypotension, pruritus, urinary retention, and motor blockade. Technical failures occurred in 6.1% of patients. Conclusions:In adults having surgery under general anesthesia, concomitant epidural analgesia reduces postoperative mortality and improves a multitude of cardiovascular, respiratory, and gastrointestinal morbidity endpoints compared with patients receiving systemic analgesia. Because adverse effects and technical failures cannot be ruled out, individual risk–benefit analyses and professional care are recommended.

Clonidine as an adjuvant to local anesthetics for peripheral nerve and plexus blocks: a meta-analysis of randomized trials.

The effect of adding clonidine to local anesthetics for nerve or plexus blocks remains unclear. The authors searched for randomized placebo-controlled trials testing the impact of adding clonidine to local anesthetics for peripheral single-injection nerve or plexus blocks in adults undergoing any surgery (except eye) without general anesthesia. Twenty trials (1,054 patients, 573 received clonidine) published 1992–2006 tested plexus (14 brachial, 1 cervical) and nerve blocks (2 sciatic/femoral, 1 midhumeral, 1 ilioinguinal/iliohypogastric, 1 ankle). Clonidine doses ranged from 30 to 300 μg; most patients received 150 μg. Clonidine prolonged the duration of postoperative analgesia (weighted mean difference 122 min; 95% confidence interval [CI] 74–169), sensory block (weighted mean difference 74 min; 95% CI 37–111), and motor block (weighted mean difference 141 min; 95% CI 82–199). In a subgroup of patients receiving an axillary plexus block, these effects were independent of whether clonidine was added to an intermediate or a long-acting local anesthetic. Clonidine increased the risk of arterial hypotension (odds ratio 3.61; 95% CI 1.52–8.55; number-needed-to-harm 11), orthostatic hypotension or fainting (odds ratio 5.07; 95% CI 1.20–21.4; number-needed-to-harm 10), bradycardia (odds ratio 3.09; 95% CI 1.10–8.64; number-needed-to-harm 13), and sedation (odds ratio 2.28; 95% CI 1.15–4.51; number-needed-to-harm 5). There was a lack of evidence of dose-responsiveness for beneficial or harmful effects. Clonidine added to intermediate or long-acting local anesthetics for single-shot peripheral nerve or plexus blocks prolongs duration of analgesia and motor block by about 2 h. The increased risk of hypotension, fainting, and sedation may limit its usefulness. Dose-responsiveness remains unclear.

Opioids added to local anesthetics for single-shot intrathecal anesthesia in patients undergoing minor surgery: a meta-analysis of randomized trials

Summary Morphine, and to a lesser extent fentanyl, added to intrathecal bupivacaine prolong postoperative analgesia. With morphine, the risk of respiratory depression cannot be ruled out. Abstract Opioids are widely used as additives to local anesthetics for intrathecal anesthesia. Benefit and risk remain unclear. We systematically searched databases and bibliographies to February 2011 for full reports of randomized comparisons of any opioid added to any intrathecal local anesthetic with the local anesthetic alone in adults undergoing surgery (except cesarean section) and receiving single‐shot intrathecal anesthesia without general anesthesia. We included 65 trials (3338 patients, 1932 of whom received opioids) published between 1983 and 2010. Morphine (0.05–2 mg) and fentanyl (10–50 μg) added to bupivacaine were the most frequently tested. Duration of postoperative analgesia was prolonged with morphine (weighted mean difference 503 min; 95% confidence interval [CI] 315 to 641) and fentanyl (weighted mean difference 114 min; 95% CI 60 to 168). Morphine decreased the number of patients needing opioid analgesia after surgery and decreased pain intensity to the 12th postoperative hour. Morphine increased the risk of nausea (number needed to harm [NNH] 9.9), vomiting (NNH 10), urinary retention (NNH 6.5), and pruritus (NNH 4.4). Fentanyl increased the risk of pruritus (NNH 3.3). With morphine 0.05 to 0.5 mg, the NNH for respiratory depression varied between 38 and 59 depending on the definition of respiratory depression chosen. With fentanyl 10 to 40 μg, the risk of respiratory depression was not significantly increased. For none of these effects, beneficial or harmful, was there evidence of dose‐responsiveness. Consequently, minimal effective doses of intrathecal morphine and fentanyl should be sought. For intrathecal buprenorphine, diamorphine, hydromorphone, meperidine, methadone, pentazocine, sufentanil, and tramadol, there were not enough data to allow for meaningful conclusions.

Combination of a reduced dose of an intrathecal local anesthetic with a small dose of an opioid: A meta-analysis of randomized trials

&NA; Adding an opioid to a reduced dose of an intrathecal local anesthetic decreases the risk of local anesthetic–related adverse effects without compromising analgesia. &NA; We tested whether the combination of a reduced dose of a local anesthetic (LA) with an opioid compared with a standard dose of the same LA alone guaranteed adequate intraoperative anesthesia and postoperative analgesia and decreased LA‐related adverse effects. We systematically searched (to November 2012) for randomized comparisons of combinations of a reduced dose of an LA with a concomitant opioid (experimental) with a standard dose of the LA alone (control) in adults undergoing surgery with single‐injection intrathecal anesthesia without general anesthesia. We included 28 trials (1393 patients). In experimental groups, the median decrease in LA doses was 40% (range, 12%–70%). There was no difference between experimental and control groups in the need for intraoperative opioids or general anesthesia for failed block or in the duration of postoperative analgesia. With experimental interventions, there was evidence of a reduction in the duration of motor blockade postoperatively (average, −50 minutes), time to discharge from hospital or PACU (−33 minutes), time to ambulation (−28 minutes), and time to urination (−14 minutes). There was also evidence of a decrease in the risk of shivering (risk ratio [RR]: 0.26; 95% confidence interval [CI]: 0.12–0.56), nausea (RR: 0.45; 95% CI: 0.31–0.66), and arterial hypotension (RR: 0.52; 95% CI: 0.35–0.78). The risk of pruritus was increased (RR: 11.7; 95% CI: 6.2–21.9). Adding an opioid to a reduced dose of an intrathecal LA can decrease LA‐related adverse effects and improve recovery from the spinal block without compromising intraoperative anesthesia or duration of postoperative analgesia.

Ability of a meta-analysis to prevent redundant research: systematic review of studies on pain from propofol injection

Objective To examine whether, according to the conclusions of a 2000 systematic review with meta-analysis on interventions to prevent pain from propofol injection that provided a research agenda to guide further research on the topic, subsequently published trials were more often optimally blinded, reported on children, and used the most efficacious intervention as comparator; and to check whether the number of new trials published each year had decreased and whether the designs of trials that cited the review differed from those that did not. Study design Systematic review comparing old trials (published before, and included in, the review) with new trials (published afterwards). Data sources Medline, Cochrane, Embase, and bibliographies to January 2013. Eligibility criteria for study selection Randomised studies testing any intervention to prevent pain from propofol injection in humans. Results 136 new trials (19 778 patients) were retrieved. Compared with the 56 old trials (6264 patients), the proportion of optimally blinded trials had increased from 10.7% to 38.2% (difference 27.5%, 95% confidence interval 16.0% to 39.0%, P<0.001), and the proportion of trials that used the most efficacious intervention as comparator had increased from 12.5% to 27.9% (difference 15.4%, 4.0% to 26.9%, P=0.022). The proportion of paediatric trials had increased from 5.4% to 12.5%, although this was not significant (difference 7.1%, −1.0% to 15.2%, P=0.141). The number of new trials published each year was significantly higher (median number/year 12 (range 7-20) v 2.5 (0-9), P<0.001) with no obvious decreasing trend. 72.8% (n=99) of the new trials cited the review, with their designs similar to trials not citing the review. Only 36.0% (n=49) of the new trials were considered clinically relevant since they used the most efficacious intervention as comparator or included a paediatric population. Conclusions The impact of the systematic review on the design of subsequent research was low. There was an improvement in the reporting of optimal blinding procedures and a tendency towards an increase in the proportion of paediatric trials. The most efficacious intervention was more often chosen as comparator but remained marginally used, and the number of trials published per year had not decreased. The use of systematic reviews should be encouraged to inform rational, and thus ethical, trial design and improve the relevance of new research.

How do authors of systematic reviews deal with research malpractice and misconduct in original studies? A cross-sectional analysis of systematic reviews and survey of their authors

Objectives To study whether systematic reviewers apply procedures to counter-balance some common forms of research malpractice such as not publishing completed research, duplicate publications, or selective reporting of outcomes, and to see whether they identify and report misconduct. Design Cross-sectional analysis of systematic reviews and survey of their authors. Participants 118 systematic reviews published in four journals (Ann Int Med, BMJ, JAMA, Lancet), and the Cochrane Library, in 2013. Main outcomes and measures Number (%) of reviews that applied procedures to reduce the impact of: (1) publication bias (through searching of unpublished trials), (2) selective outcome reporting (by contacting the authors of the original studies), (3) duplicate publications, (4) sponsors’ and (5) authors’ conflicts of interest, on the conclusions of the review, and (6) looked for ethical approval of the studies. Number (%) of reviewers who suspected misconduct are reported. The procedures applied were compared across journals. Results 80 (68%) reviewers confirmed their data. 59 (50%) reviews applied three or more procedures; 11 (9%) applied none. Unpublished trials were searched in 79 (66%) reviews. Authors of original studies were contacted in 73 (62%). Duplicate publications were searched in 81 (69%). 27 reviews (23%) reported sponsors of the included studies; 6 (5%) analysed their impact on the conclusions of the review. Five reviews (4%) looked at conflicts of interest of study authors; none of them analysed their impact. Three reviews (2.5%) looked at ethical approval of the studies. Seven reviews (6%) suspected misconduct; only 2 (2%) reported it explicitly. Procedures applied differed across the journals. Conclusions Only half of the systematic reviews applied three or more of the six procedures examined. Sponsors, conflicts of interest of authors and ethical approval remain overlooked. Research misconduct is sometimes identified, but rarely reported. Guidance on when, and how, to report suspected misconduct is needed.

Feasibility and efficacy of preoperative epidural catheter placement for anterior scoliosis surgery.

Background:Postoperative pain control via thoracic epidural catheters (TECs) is an important aspect of postoperative care, and ample evidence highlights its positive physiologic effects and superiority to intravenous analgesia. If epidural catheters for postoperative pain relief are used in scoliosis surgery, current practice is the intraoperative placement of the TEC by the surgeon because preoperative placement is considered challenging and dangerous. On the basis of magnetic resonance imaging of scoliotic spines, the authors developed a technique for preoperative placement of TEC and investigated its safety and feasibility. Methods:Patients undergoing anterior scoliosis surgery were included, who received preoperative placement of TEC. Postoperative pain, problems associated with the TEC placement, possible side effects, radiographic data, and insertion levels of the TEC were noted. Results:The apex vertebra was identified as a possible site for TEC placement due to dural sac shift leaving a wider epidural space on the convex side. Scoliosis-induced rotation of the vertebrae required realignment of the needle toward the convex side. Sixty patients were included. The success rate for TEC placement was 96.6%: one failed attempt, one catheter placed intrapleurally, and one patient with Horner syndrome. Seven percent of patients required additional rescue analgesia. All other patients had pain scores within acceptable limits (Visual Analogue Scale <5). Conclusions:The authors have demonstrated that it is possible to insert a TEC in patients with scoliotic spines with a high degree of success using a redesigned approach and thus provide adequate postoperative analgesia with a single epidural catheter. However, precautions have to be taken.

Early Effects of Irradiation on [123I]-IMT and [18F]-FDG Uptake in Rat C6 Glioma Cells

Background:Single-photon emission computed tomography (SPECT) using 3-[123I]-iodo-L-α-methyltyrosine ([123I]-IMT) and positron emission tomography (PET) using 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) are valuable tools for the distinction between viable tumor and radionecrosis in patients receiving radiotherapy for high-grade gliomas. However, to date, little is known about the early effects of radiation on [123I]-IMT and [18F]-FDG uptake in gliomas.Material and Methods:To determine the early effects of irradiation on [123I]-IMT and [18F]-FDG uptake in gliomas, in vitro studies were performed using rat C6 glioma cells. The glioma cells were irradiated with 20 Gy which is a common dose applied to patients receiving intraoperative radiotherapy. Subsequently, the early kinetics of [123I]-IMT and [18F]-FDG uptake in glioma cells were monitored for 3 days.Results:Micromorphometric examinations of the irradiated glioma cells revealed that about 25% of the viable cells transformed into giant cells. [123I]-IMT uptake per 105 viable glioma cells was unchanged on the 1st day post irradiation, but showed a significant increase on the 2nd and 3rd day following radiotherapy (p < 0.01). In addition, there was a moderate increase in [18F]- FDG accumulation per 105 viable glioma cells during the first 3 days after irradiation (p < 0.05). The maximum increase in early [123I]-IMT uptake 1 h after application surpassed that of [18F]-FDG (p < 0.01).Conclusion:Rat C6 glioma cells show an early increase in [123I]-IMT and [18F]-FDG uptake following irradiation which may be partly due to giant cell formation. These data suggest that [123I]-IMT SPECT and [18F]-FDG PET may be promising procedures for the early prediction of the therapeutic response of gliomas to radiotherapy.Hintergrund:Mit Hilfe der Single-Photon-Emissionscomputertomographie (SPECT) mit 3-[123I]-Iodo-L-α-Methyltyrosin ([123I]-IMT) und der Positronenemissionstomographie (PET) mit 2-[18F]-Fluor-2-Desoxy-D-Glucose ([18F]-FDG) lässt sich bei Patienten mit hochgradigen Gliomen nach einer Strahlentherapie verlässlich zwischen einem vitalen Tumor und einer Strahlennekrose differenzieren. Über die frühen Effekte einer Strahlentherapie auf die [123I]-IMT- und [18F]-FDG-Aufnahme in Gliomen ist zurzeit allerdings wenig bekannt.Material und Methodik:Um die frühen Effekte einer Radiotherapie auf die [123I]-IMT- und [18F]-FDG-Aufnahme in Gliomen zu bestimmen, wurden In-vitro-Studien an C6-Gliomzellen der Ratte durchgeführt. Die Gliomzellen wurden mit 20 Gy bestrahlt, einer Dosis, die Patienten in der Regel bei einer intraoperativen Strahlentherapie erhalten. Anschließend wurde über 3 Tage die Kinetik der [123I]-IMT- und [18F]-FDG-Aufnahme in die Gliomzellen untersucht.Ergebnisse:Mikromorphometrische Studien der bestrahlten Zellen zeigten, dass etwa 25% der überlebenden Zellen zu Riesenzellen transformiert waren. Die [123I]-IMT-Aufnahme bezogen auf 105 lebende Zellen war am 1. Tag nach der Strahlentherapie noch unverändert, zeigte dann aber am 2. und 3. Tag einen signifikanten Anstieg (p < 0,01). Ferner fand sich ein leichter Anstieg der [18F]-FDG-Aufnahme während der ersten 3 Tage nach der Strahlentherapie bezogen auf 105 lebendige Gliomzellen (p < 0,05). Dabei war die maximale Zunahme der [123I]-IMT-Aufnahme 1 h nach Applikation insgesamt größer als die der [18F]-FDG (p < 0,01).Schlussfolgerung:C6-Gliomzellen zeigen nach einer Strahlentherapie einen frühen Anstieg der [123I]-IMT- und [18F]-FDG-Aufnahme, der u. a. auf die Bildung von Riesenzellen zurückzuführen ist (Abbildungen 2b, 3b und 4b). Die Ergebnisse dieser Studie legen eine Bedeutung der [123I]-IMT-SPECT und der [18F]-FDG-PET in der frühen Erfassung des Ansprechens der Gliome auf eine Strahlentherapie nahe.