Opioids and NMDA receptors: Neuro-excitation and abnormal pain behaviours

In the clinical setting, chronic administration of high doses of systemic morphine may result in neuro-excitatory behaviours such as myoclonus and allodynia in some patients. Additionally, high doses of m-opioid agonists such as morphine administered chronically by the intrathecal route in both rats and humans, as well as DAMGO in rats, have been reported to produce neuro-excitatory behaviours. However, more recently, it has begun to be appreciated that even at normal analgesic doses, opioids such as morphine are capable not only of activating pain inhibitory systems (analgesia/antinociception), but they also activate pain facilitatory systems such that post-opioid allodynia/hyperalgesia may be evident after cessation of opioid treatment. Whilst it is well documented that opioid receptors mediate the inhibitory effects of opioid analgesics, the excitatory and pro-nociceptive effects of opioids appear to involve indirect activation of N-methyl-D-aspartate (NMDA) receptors, such that the extent of pain relief produced may be the net effect of these two opposing actions. Apart from the NMDA-nitric oxide (NO) pro-nociceptive signaling cascade, considerable evidence also implicates dynorphin A as well as the endogenous anti-opioid peptides cholecystokinin (CCK), neuropeptide FF (NPFF) and orphanin FQ/nociceptin, in mediating opioid-induced neuro-excitation and abnormal pain behaviours. Apart from the neuro-excitatory effects that may be produced by the parent opioid, systemic administration of some opioid analgesics such as morphine and hydromorphone in rats and humans results in their rapid conversion to 3-glucuronide metabolites that also contribute significantly to the neuro-excitatory and abnormal pain behaviours produced

Should topical opioid analgesics be regarded as effective and safe when applied to chronic cutaneous lesions?

Objectives: The induction of analgesia for many chronic cutaneous lesions requires treatment with an opioid analgesic. In many patients suffering with these wounds such drugs are either contraindicated or shunned because of their association with death. There are now case reports involving over 100 patients with many different types of chronic superficial wounds, which suggest that the topical application of an opioid in a suitable gel leads to a significant reduction in the level of perceived pain. Key findings: Some work has been undertaken to elucidate the mechanisms by which such a reduction is achieved. To date there have been no proven deleterious effects of such an analgesic system upon wound healing. Although morphine is not absorbed through the intact epidermis, an open wound provides no such barrier and for large wounds drug absorption can be problematic. However, for most chronic cutaneous lesions, where data has been gathered, the blood levels of the drug applied ranges from undetectable to below that required for a systemic effect. Summary If proven, the use of opioids in this way would provide adequate analgesia for a collection of wounds, which are difficult to treat in patients who are often vulnerable. Proof of this concept is now urgently required. © 2011 Royal Pharmaceutical Society.

Pharmacology and the safe prescribing of drugs

Understanding the pharmacological principles and safe use of drugs is just as important in surgical practice as in any other medical specialty. With an ageing population with often multiple comorbidities and medications, as well as an expanding list of new pharmacological treatments, it is important that surgeons understand the implications of therapeutic drugs on their daily practice. The increasing emphasis on high quality and safe patient care demands that doctors are aware of preventable adverse drug reactions (ADRs) and interactions, try to minimize the potential for medication errors, and consider the benefits and harms of medicines in their patients. This chapter examines these aspects from the view of surgical practice and expands on the implications of some of the most common medical conditions and drug classes in the perioperative period. The therapeutic care of surgical patients is obvious in many circumstances – for example, antibacterial prophylaxis, thromboprophylaxis, and postoperative analgesia. However, the careful examination of other drug therapies is often critical not only to the sustained treatment of the associated medical conditions but to the perioperative outcomes of patients undergoing surgery. The benefit–harm balance of many therapies may be fundamentally altered by the stress of an operation in one direction or the other; this is not a decision that should wait until the anaesthetist arrives for a preoperative assessment or one that should be left to junior medical or nursing staff on the ward.

Understanding the Effect of Protein Tyrosine Phosphatase Receptor Type 0 on Mammalian Sensory Development: Behavioral Studies on PTPRO Knockout Mice

Nerve development, which includes axon outgrowth and guidance, is regulated by many protein families, including receptor protein tyrosine phosphatases (RPTP's).Protein tyrosine phosphatase receptor type 0 (PTPRO) is a type III RPTP that is important for axon growth and guidance, as observed in chicks and flies. In order to examine the effects ofPTPRO on mammalian development, standard behavioral tests were used to compare mice lacking the gene for PTPRO (ROKO mice) to wild-type (WT) mice. The ROKO mice showed a significant delay in reacting to a thermal noxious stimulus, hotplate analgesia, when compared to the WT mice suggesting deficient nociceptive function. In a rotarod test for proprioceptive function the ROKO mice exhibited a significant decrease in the amount of time spent on the rotating rod than did the WT mice. Additional proprioception tests were performed including the climb, step reflex, beam, and mesh walk tests. In the climb and step (place) test, the ROKO group had a significantly lower accuracy in performing the tests than did the WT mice. Thus, mice lacking the PTPRO gene showed behavioral deficiencies that reflect impairment in sensory function, specifically for nociception and proprioception.

Análisis mediante acelerometría del patrón locomotor, tras la administración de morfina con o sin acepromacina, en el caballo

Los opiáceos producen una serie de efectos farmacológicos en los caballos entre los cuales destaca la analgesia, ejercida principalmente sobre el sistema nervioso central. No obstante, también producen otros efectos no deseados como son sedación, excitación, depresión cardio-respiratoria, disminución de la motilidad gastrointestinal, aumento de la actividad motora, leve hipertermia y, en dosis crecientes, sueño profundo y coma. El representante principal de este grupo farmacológico es la morfina, la cual ejerce un efecto analgésico muy potente en esta especie animal, haciendo que su uso sea de gran interés en la clínica equina. Actualmente, uno de los usos clínicos más interesantes de la morfina es el tratamiento del dolor ortopédico severo en el caballo. Sin embargo, el principal inconveniente es que la morfina también da lugar a las reacciones adversas generales de los opiáceos destacando las producidas sobre la actividad motora (marcha compulsiva), por lo que su uso estaría contraindicado en animales con problemas músculo esqueléticos que requieran guardar reposo. Estos efectos adversos indeseados, así como la ausencia relativa de evidencia con respecto a la producción de analgesia en caballos con enfermedades que se producen de manera natural hacen que su utilización sea más limitada y exista controversia en lo que respecta a su eficacia y uso clínico. Para controlar o prevenir los efectos indeseados de los opiáceos, éstos se pueden administrar dentro de un protocolo de neuroleptoanalgesia, es decir, administrar de manera conjunta un neuroléptico (tranquilizante o sedante) y un analgésico opioide. Esta combinación farmacológica permite reducir la excitación que producen los opiáceos, por lo que supone una buena alternativa en aquellos pacientes que requieran un efecto analgésico potente y en los que queramos evitar el riesgo que suponen algunos efectos adversos de los opiáceos...

A prospective comparison of a noninvasive cardiac output monitor versus esophageal doppler monitor for goal-directed fluid therapy in colorectal surgery patients

Copyright © 2014 International Anesthesia Research Society.BACKGROUND: Goal-directed fluid therapy (GDFT) is associated with improved outcomes after surgery. The esophageal Doppler monitor (EDM) is widely used, but has several limitations. The NICOM, a completely noninvasive cardiac output monitor (Cheetah Medical), may be appropriate for guiding GDFT. No prospective studies have compared the NICOM and the EDM. We hypothesized that the NICOM is not significantly different from the EDM for monitoring during GDFT. METHODS: One hundred adult patients undergoing elective colorectal surgery participated in this study. Patients in phase I (n = 50) had intraoperative GDFT guided by the EDM while the NICOM was connected, and patients in phase II (n = 50) had intraoperative GDFT guided by the NICOM while the EDM was connected. Each patient's stroke volume was optimized using 250- mL colloid boluses. Agreement between the monitors was assessed, and patient outcomes (postoperative pain, nausea, and return of bowel function), complications (renal, pulmonary, infectious, and wound complications), and length of hospital stay (LOS) were compared. RESULTS: Using a 10% increase in stroke volume after fluid challenge, agreement between monitors was 60% at 5 minutes, 61% at 10 minutes, and 66% at 15 minutes, with no significant systematic disagreement (McNemar P > 0.05) at any time point. The EDM had significantly more missing data than the NICOM. No clinically significant differences were found in total LOS or other outcomes. The mean LOS was 6.56 ± 4.32 days in phase I and 6.07 ± 2.85 days in phase II, and 95% confidence limits for the difference were -0.96 to +1.95 days (P = 0.5016). CONCLUSIONS: The NICOM performs similarly to the EDM in guiding GDFT, with no clinically significant differences in outcomes, and offers increased ease of use as well as fewer missing data points. The NICOM may be a viable alternative monitor to guide GDFT.

Comparison between local anaesthetic agents, lidocaine and bupivacaine, in patients undergoing third molar extraction in terms of patient satisfaction.

AIMS: (1) To determine if anaesthetic agent bupivacaine, has a prolonged effect on the period of acute postoperative pain when compared to lidocaine, a shorter acting agent. (2) To determine patient’s post-operative satisfaction and preference with regard to anaesthetic choice. METHODS: This double blind, randomised, interventional clinical trial included 85 patients. All patients had bilateral impacted lower third molars of removed under general anaesthetic. All patients received 0.5% plain bupivacaine on one randomly allocated side, with 2% lidocaine (with adrenaline) administered on the opposite side. Pain was measured using visual analogue scales at 0, 30, 60 minutes and 3, 4, 6 and 8 hours post-surgery. Pain was analysed for 1 week following surgery. Psychological evaluations and patient reported outcomes, including patient satisfaction were evaluated. RESULTS: A significant difference in pain (P=0.001) was seen during the 3-8 hour post-operative period. The upper limit of the 95% confidence interval was 10.0 or above at 3hours and 4 hours post-surgery. Two-thirds of patients preferred bupivacaine. CONCLUSION: Longer lasting anaesthetics such as bupivacaine offer a longer period of analgesia, and improve overall patient satisfaction.

Postoperative analgesic effect, of preoperatively administered dexamethasone, after operative fixation of fractured neck of femur: randomised, double blinded controlled study.

Background: Fractured neck of femur is a common cause of hospital admission in the elderly and usually requires operative fixation. In a variety of clinical settings, preoperative glucocorticoid administration has improved analgesia and decreased opioid consumption. Our objective was to define the postoperative analgesic efficacy of single dose of dexamethasone administered preoperatively in patients undergoing operative fixation of fractured neck of femur. Methods: Institutional ethical approval was granted and written informed consent was obtained from each patient. Patients awaiting for surgery at Cork University Hospital were recruited between July 2009 and August 2012. Participating patients, scheduled for surgery were randomly allocated to one of two groups (Dexamethasone or Placebo). Patients in the dexamethasone group received a single dose of intravenous dexamethasone 0.1 mg kg -1 immediately preoperatively. Patients in the placebo group received the same volume of normal saline. Patients underwent operative fixation of fractured neck of femur using standardised spinal anaesthesia and surgical techniques. The primary outcome was pain scores at rest 6 h after the surgery. Results: Thirty seven patients were recruited and data from thirty patients were analysed. The groups were similar in terms of patient characteristics. Pain scores at rest 6 h after the surgery (the principal outcome) were lesser in the dexamethasone group compared with the placebo group [0.8(1.3) vs. 3.9(2.9), mean(SD) p = 0.0004]. Cumulative morphine consumption 24 h after the surgery was also lesser in the dexamethasone group [7.7(8.3) vs. 15.1(9.4), mean(SD) mg, p = 0.04]. Conclusions: A single dose of intravenous dexamethasone 0.1 mg kg -1 administered before operative fixation of fractured neck of femur improve significantly the early postoperative analgesia. Trial registration: ClinicalTrials.gov identifier: NCT01550146, date of registration: 07/03/2012

Nurses' experiences of pain management for people with advanced dementia approaching the end of life: a qualitative study

AIMS AND OBJECTIVES: To explore hospice, acute care and nursing home nurses' experiences of pain management for people with advanced dementia in the final month of life. To identify the challenges, facilitators and practice areas requiring further support.

BACKGROUND: Pain management in end-stage dementia is a fundamental aspect of end of life care; however, it is unclear what challenges and facilitators nurses experience in practice, whether these differ across care settings, and whether training needs to be tailored to the context of care.

DESIGN: A qualitative study using semi-structured interviews and thematic analysis to examine data.

METHODS: 24 registered nurses caring for people dying with advanced dementia were recruited from ten nursing homes, three hospices, and two acute hospitals across a region of the United Kingdom. Interviews were conducted between June 2014 and September 2015.

RESULTS: Three core themes were identified: challenges administering analgesia, the nurse-physician relationship, and interactive learning and practice development. Patient-related challenges to pain management were universal across care settings; nurse- and organisation-related barriers differed between settings. A need for interactive learning and practice development, particularly in pharmacology, was identified.

CONCLUSIONS: Achieving pain management in practice was highly challenging. A number of barriers were identified; however, the manner and extent to which these impacted on nurses differed across hospice, nursing home and acute care settings. Needs-based training to support and promote practice development in pain management in end-stage dementia is required.

RELEVANCE TO CLINICAL PRACTICE: Nurses considered pain management fundamental to end of life care provision; however, nurses working in acute care and nursing home settings may be under-supported and under-resourced to adequately manage pain in people dying with advanced dementia. Nurse-to-nurse mentoring and ongoing needs-assessed interactive case-based learning could help promote practice development in this area. Nurses require continuing professional development in pharmacology. This article is protected by copyright. All rights reserved.

Implementing change in practice: Part 2- the change process

Pain management in premature and sick babies has long been recognisedas a vital component of neonatal care; however practices pertaining to painassessment and administration of analgesia remain variable in Neonatal Units(NNU). Sucrose has been identified as an effective agent in reducing pain during minorpainful procedures in premature babies but the uptake has been modest.This article (part 2) follows on from an earlier article on evidence to support theimplementation of sucrose administration as a measure for pain relief for minorprocedures (part 1) and will centre on practice-based change in the NNU and reflecton the strategies used as well as the effectiveness of the proposed change. A theoreticalchange model will be used as a framework to help unpack the influencesinherent within the change process.

A terapia da realidade virtual e a pessoa queimada: redução da dor nos cuidados à ferida -Uma revisão integrativa da literatura

Introdução: Terapias farmacológicas não têm conseguido um controle efetivo da dor na pessoa queimada nas três dimensões da dor aquando os cuidados à ferida. Assim, a Terapia da Realidade Virtual (TRV) baseia-se numa abordagem tecnológica que isola a pessoa do mundo real, visualizando apenas um ambiente virtual. Objetivo: Nesta Revisão Integrativa da Literatura pretende-se: identificar se a aplicação da TRV reduz a dor nas três dimensões aquando os cuidados à ferida; verificar em que medida a aplicação da TRV reduz a dor em cada uma das três dimensões de dor; verificar se a aplicação da TRV permite a redução de administração da analgesia opioide. Método: Efetuou-se pesquisa em motores de busca online, num período temporal de dez anos por meio de descritores e critérios de inclusão predefinidos. Definiu-se como questão de investigação "Qual é a eficácia da aplicação da Terapia da Realidade Virtual na redução da dor nos cuidados à ferida à pessoa numa unidade de queimados?". Na consecução deste trabalho, teve-se como método os Sete Passos do Cochrane Handbook, sendo incluídos seis artigos. Resultados: Pela análise dos resultados, evidencia-se a redução da dor nas três dimensões, na maioria dos estudos, quando associada a TRV a terapias farmacológicas. Conclusões: Propõem-se mais estudos randomizados controlados para definir os benefícios da TRV, comparativamente com terapias não farmacológicas menos dispendiosas.

Eficacia de la ropivacaína 0,1% intraperitoneal en el control del dolor postoperatorio en cirugía ginecológica laparoscópica

Introducción: Determinar la eficacia de la administración preincisional de ropivacaína al 0,1 % intraperitoneal en el control del dolor abdominal y/o de hombro, durante la primera semana de la cirugía laparoscópica ginecológica benigna. Diseño: Ensayo clínico aleatorizado y doble ciego. Material y métodos: Se realizó un ensayo clínico aleatorizado y doble ciego donde participaron 64 pacientes ASA I-III sometidas a cirugía laparoscópica ginecológica por patología benigna. Tras la realización del neumoperitoneo, se administraron 100 ml de ropivacaína 0,1 % o suero fisiológico intraperitoneal, dependiendo del grupo al que pertenecieran. Las pacientes recibieron, además, AINE junto con una bomba de PCA con opción de morfina de rescate como analgesia multimodal asociada. Se evaluó el dolor abdominal y/o de hombro al despertar, en reposo y en movimiento, a los 5, 30, 60 y 120 minutos, así como a las 24 horas. Se registró el consumo de morfina en las primeras 24 horas y la incidencia de náuseas y/o vómitos postoperatorios. A la semana, mediante encuesta telefónica, se registró la presencia de dolor de hombro a partir de las 24 horas, así como de dolor abdominal persistente al 7º día. Resultados: No se observaron diferencias significativas en el ENV durante las primeras 24 horas. Tampoco se observaron diferencias en el consumo de morfina, en la incidencia de náuseas y/o vómitos o en el dolor de hombro. Se evidenciaron diferencias estadísticamente significativas en la incidencia de dolor abdominal persistente al 7º día (18,52 % en grupo tratamiento vs. 57,58 % en grupo control con p = 0,04). Conclusiones: La administración intraperitoneal preincisional de 100 ml de ropivacaína 0,1 % en comparación con la administración de suero fisiológico, en el contexto de una técnica anestésica y analgésica multimodal, no ha demostrado reducir el dolor postoperatorio, el consumo de opioides ni la incidencia de náuseas y vómitos postoperatorios en las primeras 24 horas. Tampoco ha demostrado reducción del dolor de hombro a partir del primer día tras cirugía laparoscópica ginecológica. El uso de ropivacaína al 0,1 % intraperitoneal preincisional presenta una disminución estadísticamente significativa en la incidencia de dolor abdominal persistente al séptimo día de postoperatorio.

Uso del parche de lidocaína al 5% para el tratamiento del dolor postquirúrgico en cirugía de tórax

Una analgesia inadecuada en cirugía torácica facilita las complicaciones respiratorias potencialmente graves y se asocia al síndrome de dolor crónico post-toracotomía. El catéter epidural y el catéter paravertebral son los tratamientos que resultan más efectivos, dentro de una estrategia multimodal. El parche de lidocaína 5% está indicado para el dolor en la neuropatía post-herpética. Existe literatura sobre su utilidad en otros modelos de dolor. Presentamos tres pacientes con dolor postquirúrgico en cirugía de tórax, a pesar del tratamiento convencional, y su buena respuesta analgésica tras la aplicación de parche de lidocaína 5%.