Kamen V. Vlassakov

No evidence of real progress in treatment of acute pain, 1993–2012: scientometric analysis

Over the past 2 decades, many new techniques and drugs for the treatment of acute pain have achieved widespread use. The main aim of this study was to assess the progress in their implementation using scientometric analysis. The following scientometric indices were used: 1) popularity index, representing the share of articles on a specific technique (or a drug) relative to all articles in the field of acute pain; 2) index of change, representing the degree of growth in publications on a topic compared to the previous period; and 3) index of expectations, representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed. Publications on specific topics (ten techniques and 21 drugs) were assessed during four time periods (1993–1997, 1998–2002, 2003–2007, and 2008–2012). In addition, to determine whether the status of routine acute pain management has improved over the past 20 years, we analyzed surveys designed to be representative of the national population that reflected direct responses of patients reporting pain scores. By the 2008–2012 period, popularity index had reached a substantial level (≥5%) only with techniques or drugs that were introduced 30–50 years ago or more (epidural analgesia, patient-controlled analgesia, nerve blocks, epidural analgesia for labor or delivery, bupivacaine, and acetaminophen). In 2008–2012, promising (although modest) changes of index of change and index of expectations were found only with dexamethasone. Six national surveys conducted for the past 20 years demonstrated an unacceptably high percentage of patients experiencing moderate or severe pain with not even a trend toward outcome improvement. Thus, techniques or drugs that were introduced and achieved widespread use for acute pain management within the past 20 years have produced no changes in scientometric indices that would indicate real progress and have failed to improve national outcomes for relief of acute pain. Two possible reasons for this are discussed: 1) the difference between the effectiveness of old and new techniques is not clinically meaningful; and 2) resources necessary for appropriate use of new techniques in routine pain management are not adequate.

Local Anesthetic Blockade of Peripheral Nerves for Treatment of Neuralgias: Systematic Analysis

BACKGROUND: Nerve blocks with local anesthetics have been used in the diagnosis and treatment of neuralgias. Usually these blocks were administered in combination with corticosteroids and other drugs that can be effective by themselves. Although lasting benefits from nerve blocks in neuralgias have long been described, definitive evidence is lacking. We had the following objectives in this systematic review: to analyze the evidence behind the practice of peripheral nerve blockade with local anesthetics in patients with neuralgias and radicular pain syndromes; to assess the duration of pain relief after conduction block resolution; and to evaluate the effectiveness of the treatment of these syndromes with a series of blocks. METHODS: We searched Medline, Embase, narrative reviews, and book chapters. Only articles published in English were collected. The list of 3347 identified articles was reduced to 39 articles that were read entirely, 12 of which met inclusion criteria. RESULTS: Twelve included articles were analyzed. Each can be classified as a single case report or case series; there were no controlled studies among them. Nine reports assessed a single block outcome; all recorded pain relief beyond the duration of conduction blockade. Those 9 reports represented a total of 69 patients, 30 of whom had complete pain relief and 10 had relief ≥50%. Seven reports with the assessment of continuous pain ≥1 week after a single block reported complete or profound pain relief in 11 of 17 patients. All 3 reports with the assessment of a series of blocks in a large number of patients (total of 270) reported overall positive results. CONCLUSION: Because all reviewed articles were only single case reports or case series, no reliable conclusion could be drawn concerning the effectiveness of nerve blocks with local anesthetics in neuralgia. However, 2 features of the analyzed reports—the large magnitude of the effect and the high consistency of the reported outcome—indicate that future research efforts are warranted.

N-phenylethyl amitriptyline in rat sciatic nerve blockade

Background The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na+ channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus–discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties. Methods The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model. Results In vitro, N-phenylethyl amitriptyline at 10 &mgr;m elicits a greater block of Na+ channels than amitriptyline (resting block of approximately 90%vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 ± 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 ± 3 min for lidocaine at 37 mm (n = 4; mean ± SEM). However, there was evidence of neurotoxicity at 5 mm. Conclusion N-phenylethyl amitriptyline appears to have a narrow therapeutic range but is much more potent than lidocaine, providing a block duration several times longer than any clinically used local anesthetic. Further work in animal models of neuropathic pain will assess the potential use of this drug.

Vassily von Anrep, Forgotten Pioneer of Regional Anesthesia

Vassily von Anrep, Forgotten Pioneer of Regional Anesthesia Steve Yentis;Kamen Vlassakov; Anesthesiology

The ultrasound-guided retrolaminar block

PurposeParavertebral blocks have gained in popularity and offer the possible benefit of reduced adverse effects when compared with epidural analgesia. Nevertheless, pulmonary complications in the form of inadvertent pleural puncture are still a recognized risk. Also, the traditional paravertebral blocks are often technically difficult even with ultrasound guidance and constitute deep non-compressible area injections. We present our experience with the first three patients receiving ultrasound-guided retrolaminar blocks for managing the pain associated with multiple rib fractures.Clinical featuresThe vertebral laminae are identified by ultrasound imaging in a paramedian sagittal plane by sequentially visualizing the pleura and ribs, transverse processes, and the corresponding laminae (from lateral to medial). The block needle is guided to contact the lamina, and the local anesthetic injectate is visualized under real-time imaging. A catheter is inserted and used for continuous analgesia. In three consecutive patients, verbal rating scale (VRS) pain scores were reduced from 10/10 to less than 5/10, and no technical difficulties, complications, or adverse effects were encountered.ConclusionsSuccessful analgesia was achieved in all three cases utilizing continuous infusion and intermittent boluses with ultrasound-guided retrolaminar blocks. These results show the feasibility of this approach for patients with multiple rib fractures.RésuméObjectifLes blocs paravertébraux ont gagné en popularité et offrent l’avantage de réduire potentiellement les effets secondaires comparativement à l’analgésie péridurale. Toutefois, les complications pulmonaires, sous forme de ponction pleurale involontaire, demeurent un risque bien connu. En outre, les blocs paravertébraux conventionnels sont souvent difficiles à réaliser d’un point de vue technique et ce, même sous échoguidage, étant donné qu’il s’agit d’injections profondes réalisées dans des zones non compressibles. Nous rapportons notre expérience auprès des trois premiers patients à recevoir un bloc rétrolaminaire échoguidé pour la prise en charge de la douleur associée à une fracture multiple des côtes.Éléments cliniquesLes lames vertébrales sont identifiées par ultrason dans un plan sagittal paramédian en visualisant la plèvre et les côtes, les apophyses transverses, et les lames correspondantes (des lames latérales aux médiales) séquentiellement. L’aiguille du bloc est guidée jusqu’à ce qu’elle atteigne la lame, et l’anesthésique local injecté est visualisé par imagerie en temps réel. Un cathéter est inséré et utilisé pour l’analgésie en continu. Chez trois patients consécutifs, les scores de douleur sur une échelle visuelle ont baissé de 10/10 à moins de 5/10, et aucune difficulté technique, complication ou effet secondaire n’a été rapporté.ConclusionDans les trois cas, l’analgésie a été réalisée grâce à une perfusion continue et des bolus intermittents avec des blocs rétrolaminaires échoguidés. Ces résultats montrent la faisabilité de cette approche pour les patients présentant des fractures multiples des côtes.

Scientometrics of anesthetic drugs and their techniques of administration, 1984–2013

The aim of this study was to assess progress in the field of anesthetic drugs over the past 30 years using scientometric indices: popularity indices (general and specific), representing the proportion of articles on a drug relative to all articles in the field of anesthetics (general index) or the subfield of a specific class of anesthetics (specific index); index of change, representing the degree of growth in publications on a topic from one period to the next; index of expectations, representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed; and index of ultimate success, representing a publication outcome when a new drug takes the place of a common drug previously used for the same purpose. Publications on 58 topics were assessed during six 5-year periods from 1984 to 2013. Our analysis showed that during 2009–2013, out of seven anesthetics with a high general popularity index (≥2.0), only two were introduced after 1980, ie, the inhaled anesthetic sevoflurane and the local anesthetic ropivacaine; however, only sevoflurane had a high index of expectations (12.1). Among anesthetic adjuncts, in 2009–2013, only one agent, sugammadex, had both an extremely high index of change (>100) and a high index of expectations (25.0), reflecting the novelty of its mechanism of action. The index of ultimate success was positive with three anesthetics, ie, lidocaine, isoflurane, and propofol, all of which were introduced much longer than 30 years ago. For the past 30 years, there were no new anesthetics that have produced changes in scientometric indices indicating real progress.

A Comparison of Web-Based with Traditional Classroom-Based Training of Lung Ultrasound for the Exclusion of Pneumothorax

BACKGROUND:Lung ultrasound (LUS) is a well-established method that can exclude pneumothorax by demonstration of pleural sliding and the associated ultrasound artifacts. The positive diagnosis of pneumothorax is more difficult to obtain and relies on detection of the edge of a pneumothorax, called the “lung point.” Yet, anesthesiologists are not widely taught these techniques, even though their patients are susceptible to pneumothorax either through trauma or as a result of central line placement or regional anesthesia techniques performed near the thorax. In anticipation of an increased training demand for LUS, efficient and scalable teaching methods should be developed. In this study, we compared the improvement in LUS skills after either Web-based or classroom-based training. We hypothesized that Web-based training would not be inferior to “traditional” classroom-based training beyond a noninferiority limit of 10% and that both would be superior to no training. Furthermore, we hypothesized that this short training session would lead to LUS skills that are similar to those of ultrasound-trained emergency medicine (EM) physicians. METHODS:After a pretest, anesthesiologists from 4 academic teaching hospitals were randomized to Web-based (group Web), classroom-based (group class), or no training (group control) and then completed a posttest. Groups Web and class returned for a retention test 4 weeks later. All 3 tests were similar, testing both practical and theoretical knowledge. EM physicians (group EM) performed the pretest only. Teaching for group class consisted of a standardized PowerPoint lecture conforming to the Consensus Conference on LUS followed by hands-on training. Group Web received a narrated video of the same PowerPoint presentation, followed by an online demonstration of LUS that also instructs the viewer to perform an LUS on himself using a clinically available ultrasound machine and submit smartphone snapshots of the resulting images as part of a portfolio system. Group Web received no other hands-on training. RESULTS:Groups Web, class, control, and EM contained 59, 59, 20, and 42 subjects. After training, overall test results of groups Web and class improved by a mean of 42.9% (±18.1% SD) and 39.2% (±19.2% SD), whereas the score of group control did not improve significantly. The test improvement of group Web was not inferior to group class. The posttest scores of groups Web and class were not significantly different from group EM. In comparison with the posttests, the retention test scores did not change significantly in either group. CONCLUSIONS:When training anesthesiologists to perform LUS for the exclusion of pneumothorax, we found that Web-based training was not inferior to traditional classroom-based training and was effective, leading to test scores that were similar to a group of clinicians experienced in LUS.

Changes in Publication-Based Academic Interest in Local Anesthetics Over the Past 50 Years

PURPOSE To present the history of changes in academic interest in local anesthetics quantitatively. METHODS The changes in publication-based academic interest in local anesthetics were assessed using information from the database of PubMed. The assessment was mostly based on the following indices: general popularity index (GPI), representing the proportion of articles on a drug relative to all articles in the field of regional anesthesia, and specific popularity index (SPI), representing the proportion of articles on a drug relative to all articles in one of the four forms of regional anesthesia: local anesthesia, spinal anesthesia, epidural anesthesia, and peripheral nerve blocks. RESULTS The most important general feature of the changes in publication-based academic interest in local anesthetics for the past 50 years was the concentration of this interest on a very limited number of drugs. By 2010-2014, only three anesthetics demonstrated the GPI value above 4.0: bupivacaine (10.1), lidocaine (10.0), and ropivacaine (4.6). All other local anesthetics had GPI declining mostly to less than 1.0 (2010-2014). The rate of change in publication-based academic interest was very slow in both its increase and decline. The most profound change in publication-based academic interests was caused by the introduction of bupivacaine. During a 20-year period (from 1965-1969 to 1985-1989), bupivacaines GPI increased from 1.3 to 12.9. CONCLUSION A slowly developing concentration of publication-based academic interest on a very limited number of local anesthetics was the dominant feature related to this class of anesthetic agents.

Decline in the Development of New Anesthetics.

The number of new anesthetics approved by the USA FDA over the past 30 years (1985-2014) is much smaller than during the preceding 30 years (1955-1984): four versus ten. Investigational anesthetics clinically tested since 1990 have been almost exclusively intravenous anesthetics (nine compounds), with only one now approved by the FDA. All nine agents represent modifications of anesthetics introduced approximately 40-50 years ago; none demonstrates a truly novel mechanism of action. The apparent drought of novel anesthetics is difficult to explain. While there may be multiple reasons, we believe that one is especially noteworthy: the dramatic improvement in anesthesia safety owing to the context in which anesthetics are administered, effectively decreasing the pressure to develop new drugs with better safety margins.

Ultrasound-guided retrolaminar paravertebral block

would necessarily avoid the drug error described in Muddanna et al.’s letter, and colour-coding of drugs would not have prevented any of our incidents. On our delivery suite, Syntocinon (or carbetocin depending on our guidelines) is never drawn up in advance of caesarean section and when drawn up ahead of administration, we encourage that it is kept separate from all other drugs on a different part of the anaesthetic machine. Even better would be to draw it up at the time it is needed whilst following our ten commandments. There will never be a failsafe method and colour-coding does not solve all problems, but formal teaching of our juniors is a sensible step and stressing our tenth commandment, we hope, will result in extra vigilance by the anaesthetist administering the drug.