Avaliação algimétrica por estímulo nociceptivo térmico e pressórico em cães pré-tratados com levomepromazina, midazolam e quetamina associados ou não ao butorfanol ou buprenorfina

This study aimed at quantifies the pain in dogs under dissociative anesthesia, across thermal and pressoric stimulus and quantify the reasonable period between two different opioids analgesics. In this study, 30 dogs were used and, divided into three groups of 10 animals each, in which the animals of GI received methotrimeprazine and midazolam put on the same syringe with ketamine. The animals of GII received the same treatment of GI but associated with butorphanol and finally the animals of GIII received the same treatment of GI but associated with buprenorphine. The routine parametric evaluations has been proceeded, although using the thermo algimetry measured in degrees C with the average of 52 degrees C and the pressoric algimetry in Kg. In the thermo algimetry, there has been significant difference in GI at the moments M0, M1, M4 and M5; in GII it was found at M0, M1, M5 and M6 and in GIII it was observed the significant at M0 and M1. It has also been shown in pressoric algimetry significant difference in GI at the moments M0, M2 and M3. Among GII it has observed significant difference at all moments and it has found at M0, M9 in GIII. Thus, it has observed significant differences between all groups; for such the M2 of GII smaller than the others; and M4, M5 of GIII bigger than GI and GII. In the assessment of all periods it was observed significant latent period bigger in GI, however, with reasonable period and short recovery in GII and GIII. In the order hand, the postural tonus recovery it was longer in GIII, followed by GII and finally GI. The used method for the measurement of algic stimulus was efficient, noticing a reasonable analgesic period of 3 hours for butorphanol and 6 hours for buprenorphine.

Validation of mechanical, electrical and thermal nociceptive stimulation methods in horses

To validate a model for investigating the effects of analgesic drugs on mechanical, thermal and electrical stimulation testing. To investigate repeatability, sensitivity and specificity of nociceptive tests. Randomised experiment with 2 observers in 2 phases. Mechanical (M), thermal (TL) and electrical (E) stimuli were applied to the dorsal metacarpus (M-left and TL-right) and coronary band of the left thoracic limb (E) and a thoracic thermal stimulus (TT) was applied caudal to the withers in 8 horses (405 ± 43 kg). Stimuli intensities were increased until a clear avoidance response was detected without exceeding 20 N (M), 60°C (TL and TT) and 15 V (E). For each set of tests, 3 real stimuli and one sham stimulus were applied (32 per animal) using a blinded, randomised, crossover design repeated after 6 months. A distribution frequency and, for each stimulus, Chi-square and McNemar tests compared both the proportion of positive responses detected by 2 observers and the 2 study phases. The κ coefficients estimated interobserver agreement in determining endpoints. Sensitivity (384 tests) and specificity (128 tests) were evaluated for each nociceptive stimulus to assess the evaluators' accuracy in detecting real and sham stimuli. Nociceptive thresholds were 3.1 ± 2 N (M), 8.1 ± 3.8 V (E), 51.4 ± 5.5°C (TL) and 55.2 ± 5.3°C (TT). The level of agreement after all tests, M, E, TL and TT, was 90, 100, 84, 98 and 75%, respectively. Sensitivity was 89, 100, 89, 98 and 70% and specificity 92, 97, 88, 91 and 94%, respectively. The high interobserver agreement, sensitivity and specificity suggest that M, E and TL tests are valid for pain studies in horses and are suitable tools for investigating antinociceptive effects of analgesics in horses.

Modelos lineares generalizados mistos e equações de estimação generalizadas para dados binário aplicados em anestesiologia veterinária

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação algimétrica por estímulo nociceptivo térmico e pressórico em cães pré-tratados com levomepromazina, midazolam e quetamina associados ou não ao butorfanol ou buprenorfina

This study aimed at quantifies the pain in dogs under dissociative anesthesia, across thermal and pressoric stimulus and quantify the reasonable period between two different opioids analgesics. In this study, 30 dogs were used and, divided into three groups of 10 animals each, in which the animals of GI received methotrimeprazine and midazolam put on the same syringe with ketamine. The animals of GII received the same treatment of GI but associated with butorphanol and finally the animals of GIII received the same treatment of GI but associated with buprenorphine. The routine parametric evaluations has been proceeded, although using the thermo algimetry measured in degrees C with the average of 52 degrees C and the pressoric algimetry in Kg. In the thermo algimetry, there has been significant difference in GI at the moments M0, M1, M4 and M5; in GII it was found at M0, M1, M5 and M6 and in GIII it was observed the significant at M0 and M1. It has also been shown in pressoric algimetry significant difference in GI at the moments M0, M2 and M3. Among GII it has observed significant difference at all moments and it has found at M0, M9 in GIII. Thus, it has observed significant differences between all groups; for such the M2 of GII smaller than the others; and M4, M5 of GIII bigger than GI and GII. In the assessment of all periods it was observed significant latent period bigger in GI, however, with reasonable period and short recovery in GII and GIII. In the order hand, the postural tonus recovery it was longer in GIII, followed by GII and finally GI. The used method for the measurement of algic stimulus was efficient, noticing a reasonable analgesic period of 3 hours for butorphanol and 6 hours for buprenorphine.

Assessment of Preemptive Analgesia Efficacy in Surgical Extraction of Third Molars

Background and objectives: Literature on preemptive analgesia is controversial. Reliability of results and difficult reproducibility of research contribute for non-elucidation of the subject. The aim of this study is to test the efficacy of oral ketoprofen (150 mg) preemptively administrated two days before third molar surgery, compared with postoperative administration in the same patient. Methods: Thirteen patients underwent surgical removal of bilateral third molar in two separate procedures. In a random and double blind procedure, oral ketoprofen 150 mg was administered every 12 hours two days before surgery and, after the procedure, the same drug was administered for three days. On the other side, a control (placebo) was used orally every 12 hours two days before surgery and, after the procedure, ketoprofen 150 mg was administered every 12 hours for three days. Postoperative pain was assessed by visual analogue scale, nominal scale, and amount of rescue analgesics consumed. Results: There was no statistically significant difference in postoperative pain between the preemptive treatment and control. Conclusion: In this experimental model, preemptive analgesia was not effective in reducing postoperative pain in surgical extraction of third molar compared with the postoperative administration of the same drug.

Dor nas unidades de internação de um hospital universitário

JUSTIFICATIVA E OBJETIVOS: Estudo exploratório-descritivo, transversal, com objetivo de determinar a prevalência, caracterização, localização, mensuração e discussão de medidas farmacológicas analgésicas em dor aguda em cinco unidades de internação de um hospital universitário. MÉTODO: Participaram 856 sujeitos, dos quais 272 com dor no momento. As informações relacionadas à dor foram obtidas através de entrevista estruturada junto ao leito. Usou-se a escala numérica de dor e diagrama corporal. RESULTADOS: A analgesia foi verificada no prontuário. A prevalência geral de dor foi de 31,8%, sendo intensa em 44,2% e a média de 6,6 na escala numérica de dor. O motivo principal foi traumatismo, o local mais frequente, o abdômen. O analgésico mais usado foi a dipirona em 76,1%, com/sem associação. Opioide forte foi prescrito em 4,4%. Para 27,5% não houve melhoria. CONCLUSÃO: Conclui-se que a dor é de alta prevalência, pouco avaliada, subtratada, com uso incorreto de analgésicos.

Chronic pain associated with the Chikungunya Fever: long lasting burden of an acute illness

Abstract Background Chikungunya virus (CHIKV) is responsible for major epidemics worldwide. Autochthonous cases were recently reported in several European countries. Acute infection is thought to be monophasic. However reports on chronic pain related to CHIKV infection have been made. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. Neuropathic pain syndromes require specific treatment and the identification of neuropathic characteristics (NC) in a pain syndrome is a major step towards pain control. Methods We carried out a cross-sectional study at the end of the major two-wave outbreak lasting 17 months in Réunion Island. We assessed pain in 106 patients seeking general practitioners with confirmed infection with the CHIK virus, and evaluated its impact on quality of life (QoL). Results The mean intensity of pain on the visual-analogical scale (VAS) was 5.8 ± 2.1, and its mean duration was 89 ± 2 days. Fifty-six patients fulfilled the definition of chronic pain. Pain had NC in 18.9% according to the DN4 questionnaire. Conversely, about two thirds (65%) of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0). However, the total score of the Short Form-McGill Pain Questionnaire (SF-MPQ)(15.5 ± 5.2 vs 11.6 ± 5.2; p < 0.01) and both the affective (18.8 ± 6.2 vs 13.4 ± 6.7; p < 0.01) and sensory subscores (34.3 ± 10.7 vs 25.0 ± 9.9; p < 0.01) were significantly higher in patients with NC. The mean pain interference in life activities calculated from the Brief Pain Inventory (BPI) was significantly higher in patients with chronic pain than in patients without it (6.8 ± 1.9 vs 5.9 ± 1.9, p < 0.05). This score was also significantly higher in patients with NC than in those without such a feature (7.2 ± 1.5 vs 6.1 ± 1.9, p < 0.05). Conclusions There exists a specific chronic pain condition associated to CHIKV. Pain with NC seems to be associated with more aggressive clinical picture, more intense impact in QoL and more challenging pharmacological treatment.

Evaluación de la presencia de compuestos farmacéuticos en aguas residuales procedentes de estaciones de depuración de aguas residuales (EDARS) de la isla de Gran Canaria

[ES]En este trabajo se ha realizado la evaluación de la concentración de compuestos farmacéuticos de uso común de diferentes grupos terapéuticos tales como, antibióticos, antiinflamatorios, analgésicos, reguladores lipídicos, betabloqueantes, antidepresivos, estimulantes y antiepilépticos, en aguas procedentes de Estaciones de Depuración de Aguas Residuales de la isla de Gran Canaria, con el fin de poner en conocimiento la situación del problema, siendo ésta un paso previo para su posible regulación y remediación. Debido a las bajas concentraciones en que estos compuestos se encuentran en las aguas residuales, para llevar a cabo el estudio, se utilizaron procesos analíticos basados en un retratamiento de la muestra utilizando la extracción en fase sólida y su posterior determinación por técnicas instrumentales de altas prestaciones

The nociceptive withdrawal reflex: Normative values of thresholds and reflex receptive fields

Assessments of spinal nociceptive withdrawal reflexes can be used in human research both to evaluate the effect of analgesics and explore pain mechanisms related to sensitization. Before the reflex can be used as a clinical tool, normative values need to be determined in large scale studies. The aim of this study was to determine the reference values of spinal nociceptive reflexes and subjective pain thresholds (to single and repeated stimulation), and of the area of the reflex receptive fields (RRF) in 300 pain-free volunteers. The influences of gender, age, height, weight, body-mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short-Form 36 (SF-36) were analyzed by multiple regressions. The 95% confidence intervals were determined for all the tests as normative values. Age had a statistically and quantitatively significant impact on the subjective pain threshold to single stimuli. The reflex threshold to single stimulus was lower on the dominant compared to the non-dominant side. Depression had a negative impact on the subjective pain threshold to single stimuli. All the other analyses either did not reveal statistical significance or displayed quantitatively insignificant correlations. In conclusion, normative values of parameters related to the spinal nociceptive reflex were determined. This allows their clinical application for assessing central hyperexcitability in individual patients. The parameters investigated explore different aspects of sensitization processes that are largely independent of demographic characteristics, cognitive and affective factors.

Reference values of mechanical and thermal pain tests in a pain-free population

Quantitative sensory tests are widely used in human research to evaluate the effect of analgesics and explore altered pain mechanisms, such as central sensitization. In order to apply these tests in clinical practice, knowledge of reference values is essential. The aim of this study was to determine the reference values of pain thresholds for mechanical and thermal stimuli, as well as withdrawal time for the cold pressor test in 300 pain-free subjects. Pain detection and pain tolerance thresholds to pressure, heat and cold were determined at three body sites: (1) lower back, (2) suprascapular region and (3) second toe (for pressure) or the lateral aspect of the leg (for heat and cold). The influences of gender, age, height, weight, body-mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short-Form 36 (SF-36) were analyzed by multiple regressions. Quantile regressions were performed to define the 5th, 10th and 25th percentiles as reference values for pain hypersensitivity and the 75th, 90th and 95th percentiles as reference values for pain hyposensitivity. Gender, age and/or the interaction of age with gender were the only variables that consistently affected the pain measures. Women were more pain sensitive than men. However, the influence of gender decreased with increasing age. In conclusion, normative values of parameters related to pressure, heat and cold pain stimuli were determined. Reference values have to be stratified by body region, gender and age. The determination of these reference values will now allow the clinical application of the tests for detecting abnormal pain reactions in individual patients.

Pharmacogenetics in palliative care

Response to analgesics, anticancer pharmacotherapy and pharmacotherapy of other cancer related symptoms vary broadly between individuals. Age, disease, comorbidities, concomitant medication, organ function and patients' compliance may partly explain the differences. However, the focus of ongoing research has shifted towards genomic variants of phase I and II drug metabolizing enzymes with one important goal being an individual dose adjustment according to a patient's genotype. Polymorphisms of the cytochrome P 450 2D6 influence the metabolism of many drugs including the analgesics codeine, tramadol, hydrocodone and oxycodone, as well as the metabolism of tricyclic antidepressants and the anticancer drug tamoxifen. Other candidate genes such as (opioid)-receptors, transporters and other molecules important for pharmacotherapy in pain management are discussed. Although pharmacogenetics as a diagnostic tool has the potential to improve patient therapy, study results are often equivocal and limited by small sample sizes and often by their retrospective design. Well designed studies are needed to demonstrate superiority of pharmoacogenetics to conventional dosing regimes.

[Prophylaxis and therapy of postdural puncture headache--a critical evaluation of treatment options]

Since the first description of spinal and epidural anaesthesia, postdural puncture headache (PDPH) is a well known complication. Its prophylaxis and treatment has been studied and discussed for more than 100 years, but the evidence is still limited. Due to relatively low prevalence of PDPH, prospective RCTs are often missing, and the frequently self-limiting character of PDPH impedes an adequate interpretation of results from studies without a control group. Taking side effects and complications into account, a prophylactic treatment of PDPH cannot be recommended. In case of PDPH, non-opioid analgesics are the first choice treatment. The epidural blood patch remains the mainstay of severe PDPH therapy. Noninvasive therapies like theophylline, sumatriptan and ACTH can be an alternative. However, an evidence-based recommendation is lacking. The development of standard operating procedures for accidental dural punctures and PDPH is recommended.

[Drug therapy of acute and chronic abdominal pain]

For drug therapy a differentiation of acute and chronic pain is essential. In emergency situations of acute abdominal pain a fast diagnosis is mandatory. Analgesia should be provided as soon as possible. The different groups of analgesics should be used according to their known effects, side effects and contraindications. Postoperative pain after abdominal surgery has to be considered as a special condition of acute abdominal pain. Main treatment options are non opioid analgesics and opioids. Opioids can be administered intravenously via patient controlled analgesia (PCA) devices. In major abdominal surgery neuroaxial analgesia, preferentially administered via an epidural catheter provides excellent pain relief with positive impact on gastrointestinal motility and patients' recovery. Because of difficulties to allocate chronic abdominal pain to a specific organ, causal treatment often turns out to be difficult. Peripheral and central sensitization, as well as an alteration of the endogenous pain modulation comes to the fore in these chronic pain conditions. Co-analgesics like anticonvulsants and antidepressants are utilized to reduce sensitization and improve the endogenous pain modulating system. Non drug approaches and alternative treatment options might be useful. In contrast, orally or transcutaneously administered opioids are the principal corner stone for the treatment of cancer pain.

Schmerzmanagement bei Kindern in der Schweiz

Hintergrund Schmerzen bei stationär aufgenommenen Kindern werden häufig unzureichend behandelt. Bisher gab es keine Informationen zum Schmerzmanagement von Kinderkrankenhäusern in der Schweiz. Ziel der vorliegenden Studie war, den aktuellen Stand der Schmerzerfassung, -interpretation und -behandlung zu bestimmen. Studiendesign Ein Fragebogen wurde an alle pädiatrischen Krankenhäuser in der Schweiz gesendet. Ergebnisse Insgesamt antworteten 27 von 45 Einheiten (Antwortrate: 60%). Die meisten Abteilungen verwenden Schmerzerfassungstools (96%) und führten diesbezügliche Leitlinien ein (78%). Die Behandlung von Schmerzen erfolgt ebenfalls meist nach hausinterner Leitlinie (78%). Prozedurale und postoperative Schmerzen werden stets (100%) analgetisch behandelt. Bei Frühgeborenen und Kindern auf Intensivpflegestationen werden bei invasiven Eingriffen häufig Analgetika (> 87%) verwendet. Auf Intensivstationen liegen in 44% diesbezügliche Leitlinien vor. Resümee Der Nutzen eines effektiven Schmerzmanagements bei Kindern ist eindeutig belegt. Viele Ansätze zur Verbesserung werden in der Schweiz gut umgesetzt. Vor allem im internationalen Vergleich verbesserte sich das Schmerzmanagement. Es gibt aber noch Optimierungsmöglichkeiten. Beispielsweise besitzen weniger als die Hälfte aller schweizerischen Intensivstationen eine Leitlinie für die Behandlung von Schmerzen bei invasiven Eingriffen.

Pharmacogenomic considerations in opioid analgesia

Translating pharmacogenetics to clinical practice has been particularly challenging in the context of pain, due to the complexity of this multifaceted phenotype and the overall subjective nature of pain perception and response to analgesia. Overall, numerous genes involved with the pharmacokinetics and dynamics of opioids response are candidate genes in the context of opioid analgesia. The clinical relevance of CYP2D6 genotyping to predict analgesic outcomes is still relatively unknown; the two extremes in CYP2D6 genotype (ultrarapid and poor metabolism) seem to predict pain response and/or adverse effects. Overall, the level of evidence linking genetic variability (CYP2D6 and CYP3A4) to oxycodone response and phenotype (altered biotransformation of oxycodone into oxymorphone and overall clearance of oxycodone and oxymorphone) is strong; however, there has been no randomized clinical trial on the benefits of genetic testing prior to oxycodone therapy. On the other hand, predicting the analgesic response to morphine based on pharmacogenetic testing is more complex; though there was hope that simple genetic testing would allow tailoring morphine doses to provide optimal analgesia, this is unlikely to occur. A variety of polymorphisms clearly influence pain perception and behavior in response to pain. However, the response to analgesics also differs depending on the pain modality and the potential for repeated noxious stimuli, the opioid prescribed, and even its route of administration.