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A history of neuraxial administrationof local analgesics and opioids

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Abstract

The history of intrathecal and epidural anaesthesia is in parallel with the development of general anaesthesia. As ether anaesthesia (1846) is considered the first modern anaesthetic since its use by Morton 157 yr ago, so Bier made history by using cocaine for intrathecal anaesthesia in 1898. The first published report on opioids for intrathecal anaesthesia belongs to a Romanian surgeon, Racoviceanu-Pitesti, who presented his experience at Paris in 1901. It was almost a century before the opioids were used for epidural analgesia. Behar and his colleagues published the first report on the epidural use of morphine for the treatment of pain in The Lancet in 1979. Epidural and intrathecal opioids are today part of a routine regimen for intra- and postoperative analgesia. Over the last 30 yr, the use of epidural opioids has became a standard for analgesia in labour and delivery, and for the management of chronic pain. Finally, epidural opioids have been shown to have a pre-emptive effect, when used before major surgery. We present the evolution of neuraxial anaesthesia and the history of intrathecal and epidural administration of opioids.

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... Another example of early recognition of the potential benefit of direct delivery to the presumptive site of opioid action was the first local spinal injections (12), initially of cocaine, in 1885 by Leonard Corning. In 1899-1901, morphine mixed with cocaine or other local anesthetic was delivered spinally by physicians on three separate continents including Dr. Matas of New Orleans (13), Dr. N. Racoviceanu-Pitesti of Romania (14), and Dr. Otojiro Kitagawa of Japan (15). The spinal site of action would remain largely underexplored until the report of morphine delivery via chronic catheterization of rat by Rudy and Yaksh in 1976 (16). ...
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Throughout history humanity has searched for an optimal approach to the use of opioids that maximizes analgesia while minimizing side effects. This review reflects upon the conceptualization of the opioid receptor and the critical role that the pharmaceutical sciences played in its revelation. Opium-containing formulations have been delivered by various routes of administration for analgesia and other therapeutic indications for millennia. The concept of a distinct site of opium action evolved as practitioners developed innovative delivery methods, such as intravenous administration, to improve therapeutic outcomes. The introduction of morphine and synthetic opioids engendered the prevalent assumption of a common opioid receptor. Through consideration of structure-activity relationships, spatial geometry, and pharmacological differences of known ligands, the idea of multiple opioid receptors emerged. By accessing the high-affinity property of naloxone, the opioid receptor was identified in central and peripheral nervous system tissue. The endogenous opioid neuropeptides were subsequently discovered. Application of mu-, delta-, and kappa- opioid receptor-selective ligands facilitated the pharmacological characterization and distinctions between the three receptors, which were later cloned and sequenced. Opioid receptor signal transduction pathways were described and attributed to specific physiological outcomes. The crystal structures of mu, delta, kappa, and nociceptin/orphanin FQ receptors bound to receptor-selective ligands have been elucidated. Comparison of these structures reveal locations of ligand binding and engagement of signal transduction pathways. Expanding knowledge regarding the structure and actions of the opioid receptor fuels contemporary strategies for driving the activity of opioid receptors toward maximizing therapeutic and minimizing adverse outcomes.
... However, morphine was not widely used until the advent of the hypodermic syringe in 1857. The first published report of intrathecal utilization of morphine was by a Romanian physician, Racoviceanu-Pitesti, in 1901 [11]. Behar and his colleagues published the first report of epidural morphine analgesia in The Lancet in 1979 [12]. ...
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Chapter
Discussion or description of spinal delivery of therapeutics typically centers on the pharmacological agent to be administered both in terms of safety and efficacy. However, the pharmaceutical preparation of such agents for spinal delivery is equally important for appropriate biodistribution of the therapeutic and for safety. The unique properties of central nervous system tissue yield formulation requirements that are different from that of other parenteral routes of administration. In this chapter, we review the specific anatomical and physiological features of the central nervous system that drive formulation principles for neuraxial delivery and detail excipient properties that are considered appropriate for solutions intended for spinal drug delivery.
Chapter
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Chapter
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Opioids administered into the spinal space by intrathecal or epidural routes can provide potent and prolonged selective analgesia. Compared to the systemic administration of opioids, spinal administration can bring about analgesia with fewer central and systemic adverse effects. For the past 40 years, spinal opioid analgesia has achieved great popularity in various fields of pain treatment. The aim of this work is to identify clinical studies that initiated the use of spinal opioids for the treatment of pain. To determine the historical role of each of the review’s studies, we used the combination of two factors: the study priority in terms of the time of its publication and the degree of its acknowledgement in the form of citation impact. The date of publication was regarded as the primary factor, but only if the count of citations indicated a sufficient acknowledgement by the other authors. The citation impact was assessed as the initial citation count – for a period of five years after the year of article publication – and the total count. Analysis of the related data shows that the clinical studies initiating the use of spinal opioids for the treatment of pain belong to two groups of authors – Wang et al. and Behar et al. Both studies were published in 1979 and described delivery of morphine into the spinal space, although the techniques of administration were different: Wang et al. injected morphine intrathecally, Behar et al. administered morphine epidurally. The response to these studies was overwhelming - close to a dozen reports on this topic were published in 1979 and more than a hundred – in 1980-1981. The total citation response to the Wang et al. article reached 699, and that to Behar et al. – 518. Two earlier records (1900-1901) of the use of intrathecal morphine, by Nicolae Racoviceanu-Pitesti and Otojiro Kitagawa, found no following in medical literature for more than three quarters of a century.
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Background There is scant clinical research on neuraxial analgesia in dogs undergoing major surgery. With this study we compared the perioperative analgesic effects of thoracic epidural anaesthesia (TEA) and intrathecal morphine (ITM) in dogs scheduled for thoracic or cranial abdominal surgery. The dogs received methadone and dexmedetomidine, were anaesthetized with propofol maintained with sevoflurane, and randomly assigned to receive either TEA (ropivacaine 0.5% at 0.2 mg/kg and morphine 0.1 mg/kg administered at T 12 -T 13 ) or ITM (morphine 30 μg/kg administered at L 6 -L 7 ). Intraoperative rescue analgesia (iRA) was fentanyl 1 μg/kg administered if heart rate or mean arterial pressure increased by 30% above the pre-stimulation level. Glasgow Pain Composite Scale score (GPCS) dictated the use of postoperative rescue analgesia (pRA) with methadone 0.2 mg/kg. Results There was a statistically significant difference in iRA, median time to first fentanyl bolus, median fentanyl dose after surgical opening, and median GPCS score at 30 minutes (min), 1 ,2, 4, 6, and 8 hours (h) between the two groups ( p< 0.001; p< 0.001; p <0.001; p< 0.01; p< 0.01; p< 0.001; p< 0.01; p= 0.01; p= 0.01, respectively). Fewer TEA than ITM group dogs required iRA during surgical opening and pRA: 5% (1/18) and 2/18 (11%), respectively, in the TEA and 83% (16/18) and 10/18 (55%), respectively, in the ITM group. Side effects were urinary retention in 3/18 (16%) TEA group dogs and 2/18 (11%) ITM group dogs and prolonged sedation in 2/18 (11%) in ITM group dogs. TEA and ITM were effective in managing perioperative pain in dogs undergoing thoracic or cranial abdominal surgery.
Chapter
The use of the subarachnoid space to drug release on neural axis is an important therapeutic alternative for managing patients with chronic pain and spasticity. Intrathecal drug delivery system (IDDS) provides direct access to the central nervous system, for small and large molecules, leading to the exact site, bypassing the blood-brain barrier. The main advantage is to provide lower drug dosages near the spinal cord receptors and powerful effect compared to different administration routes, minimizing side effects. In this chapter, we are going to discuss the main aspects of IDDS and review its use in chronic pain conditions, with focus on surgical technique.
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Background: Morphine and Dexmedetomidine have been used with subarachnoid block for postoperative pain relief, sedation and analgesia. In higher doses, it may produce adverse effect on haemodynamics. Aim and Objective: This study compares the block characteristics and side effects effects of morphine and intrathecal Dexmedetomidine, given with intrathecal bupivacaine. Materials and Methods: A prospective, randomised, double-blinded study was conducted in department of anaesthesiology at a tertiary referral hospital. Eighty patients with American Society of Anaesthesiologists Status I and II were randomly allocated to receive either dexmedetomidine (5 μg) or Morphine (200 mcg) with or 0.5% hyperbaric bupivacaine. Results: Time to first dose of rescue analgesia was significantly more with dexmedetomidine (386.75102.27 min) as compared to Morphine (232.5045.45 min). Duration of motor block was also significantly longer with dexmedetomidine (192.3836.50) than Morphine (155.488.66). There was no significant difference between the two groups in relation to onset of sensory or motor block, time to reach maximum level of sensory block, and the time for two segment regression. Conclusion: Intrathecal dexmedetomidine as compared to Morphine as an adjuvant to intrathecal bupivacaine prolonged the time to first rescue analgesia, without any significant adverse effect.
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Chapter
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Neuraxial-spinal and epidural-administration of opioids can be an effective method for controlling pain for children in a number of clinical settings. Understanding the basic pharmacologic and logistical concepts will make it easier for pediatricians to advocate for their patients, and support patients and families when circumstances suggest that neuraxial opioid treatment is appropriate. This review article summarizes the basic concepts of pharmacology, drug choice, side effects, and complications as well as situations in which neuraxial opioids are appropriate in childr en.
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The nociceptin/orphanin FQ peptide (NOP) receptor-related ligands have been demonstrated in preclinical studies for several therapeutic applications. This article highlights (1) how nonhuman primates (NHP) were used to facilitate the development and application of positron emission tomography tracers in humans; (2) effects of an endogenous NOP ligand, nociceptin/orphanin FQ, and its interaction with mu opioid peptide (MOP) receptor agonists; and (3) promising functional profiles of NOP-related agonists in NHP as analgesics and treatment for substance use disorders. NHP models offer the most phylogenetically appropriate evaluation of opioid and non-opioid receptor functions and drug effects. Based on preclinical and clinical data of ligands with mixed NOP/MOP receptor agonist activity, several factors including their intrinsic efficacies for activating NOP versus MOP receptors and different study endpoints in NHP could contribute to different pharmacological profiles. Ample evidence from NHP studies indicates that bifunctional NOP/MOP receptor agonists have opened an exciting avenue for developing safe, effective medications with fewer side effects for treating pain and drug addiction. In particular, bifunctional NOP/MOP partial agonists hold a great potential as (1) effective spinal analgesics without itch side effects; (2) safe, nonaddictive analgesics without opioid side effects such as respiratory depression; and (3) effective medications for substance use disorders.
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Intrathecal morphine (ITM) can be useful for postoperative analgesia following lower extremity joint arthroplasty, but concerns exist regarding potential dose-related side effects. In this study, we examined the safety and efficacy of ITM in patients undergoing lower extremity joint arthroplasty. We hypothesized that there would be (1) direct relationship between dosing and side effects, and (2) an inverse relationship between ITM dosing and 24-hour postoperative opioid requirement.
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In diesem Kapitel werden die Anfänge und die Geschichte der Inhalationsanalgesie in der Geburtshilfe beschrieben. Dargestellt werden z. B. erste Erfahrungen in der geburtshilflichen Anästhesie, der Opioideinsatz, die Entwicklung neuroaxialer Verfahren.
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Introduction Several analgesic modalities – pharmacological and non-pharmacological – may be used during the cesarean section postoperative period. This document focuses on the different pharmacological strategies available. Objectives To establish the advantages and disadvantages of the various pharmacological options used to control pain following a C-section, improving safety and patient satisfaction. Methods A search was done in Medline, Embase, Lilacs, and The Cochrane Library using the terms “Cesarean section”, “Cesarean pain”, “Maternal risk”, and “Analgesia for cesarean”, reviewing articles published in both English and Spanish during the last twenty years. Duplicated articles, redundant or irrelevant content, and articles with methodological flaws were excluded. Results Neuraxial opioids are widely used in postoperative cesarean section analgesia. However, they have to administered at low doses to ensure the best risk-benefit profile. The use of systemic opioids is also appropriate in these patients, reducing the occurrence of some adverse events associated with intrathecal administration. Multimodal analgesia has proven its effectiveness in postoperative pain control after cesarean delivery, significantly reducing the use of opioids and their associated adverse effects. Conclusions Notwithstanding the adverse effects described in the literature, the cornerstone of analgesia therapy after cesarean section are opioids, both neuraxial or parenteral administration. Multimodal management using NSAIDs or paracetamol, improves the safety profile and the quality of analgesia, reducing the opioid requirements.
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Resumen Introducción Durante el postoperatorio de cesárea se pueden utilizar diversas modalidades analgésicas, tanto farmacológicas como no farmacológicas. Este documento se centra en las diferentes estrategias farmacológicas disponibles. Objetivos Establecer las ventajas y desventajas de las diferentes opciones farmacológicas usadas después de la cesárea para el control del dolor, mejorando la seguridad y la satisfacción de las pacientes. Métodos Se realizó una búsqueda en Medline, Embase, Lilacs y The Cochrane Library con los términos «Cesarean section», «Cesarean pain», «Maternal risk» y «Analgesia for cesarean». Se revisaron artículos publicados en inglés y español en los últimos 20 años. Se excluyeron artículos duplicados, con contenido redundante o no pertinente, y aquellos con defectos metodológicos. Resultados Los opioides neuroaxiales son ampliamente utilizados para la analgesia postoperatoria en cesárea; sin embargo, deben usarse a dosis bajas para obtener el mejor perfil riesgo-beneficio. El uso de opioides sistémicos también es válido en estos pacientes, reduciendo la ocurrencia de algunos efectos adversos asociados a la administración intratecal. La analgesia multimodal ha demostrado ser efectiva para el control del dolor postoperatorio de cesárea, disminuyendo significativamente el consumo de opioides y los efectos adversos asociados. Conclusiones El pilar terapéutico analgésico en el postoperatorio de cesárea son los opioides, tanto en su administración neuroaxial como por vía parenteral, a pesar de los efectos adversos descritos en la literatura. El manejo multimodal con AINE o acetaminofén mejora el perfil de seguridad y la calidad de la analgesia, disminuyendo el requerimiento de opioides.
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Background and objectives Oxycodone is poorly studied as an adjuvant to central blockades. The aim of this pilot study was to assess the efficacy and safety of oxycodone hydrochloride in epidural blockade among patients undergoing total hip arthroplasty (THA). Patients and methods In 11 patients (American Society of Anesthesiologists physical status classification system II/III, age range: 59–82 years), THA was conducted with an epidural blockade using 15 mL 0.25% bupivacaine (37.5 mg) with 5 mg oxycodone hydrochloride and sedation with propofol infusion at a dose of 3–5 mg/kg/h. After the surgery, patients received ketoprofen at a dose of 100 mg twice daily. In the first 24 hours postoperative period, pain was assessed by numerical rating scale at rest and on movement; adverse effects (AEs) were recorded; and plasma concentrations of oxycodone, noroxycodone, and bupivacaine were measured. Results The administration of epidural oxycodone at a dose of 5 mg in patients undergoing THA provided analgesia for a mean time of 10.3±4.89 h. In one patient, mild pruritus was observed. Oxycodone did not evoke other AEs. Plasma concentrations of oxycodone while preserving analgesia were >2.9 ng/mL. Noroxycodone concentrations in plasma did not guarantee analgesic effect. Conclusion The administration of epidural oxycodone at a dose of 5 mg prolongs the analgesia period to ~10 hours in patients after THA. Oxycodone may evoke pruritus. A 5 mg dose of oxycodone hydrochloride used in an epidural blockade seems to be a safe drug in patients after THA.
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To use spinal opioids appropriately, it is necessary to understand the pharmacokinetics and clinical pharmacology of these drugs including which opioids produce selective spinal analgesia and which do not. Briefl y, spinal selectivity is highest for hydrophilic opioids and lowest for lipophilic opioids. These differences result from natural variations in the bioavailability of opioids at opioid receptors in the spinal cord. The bioavailability differs because lipophilic drugs are more rapidly cleared into the plasma from epidural and intrathecal spaces, than hydrophilic drugs; consequently, they produce earlier supraspinal side effects and have a considerably shorter duration of analgesic action concerning morphine which can produce delay supraspinal adverse effects. Morphine is probably the most spinally selective opioid currently used in the intrathecal and epidural spaces for the management of postoperative pain. Continuous epidural administration of fentanyl offers little or no benefit over the intravenous route. Finally, epidurally administered sufentanil and alfentanil appear to produce analgesia by systemic uptake and redistribution to brainstem opioid receptors.
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Context Different adjuvants are coadministered with local anesthetics to improve the speed of onset and duration of analgesia, and to reduce the dose, the selection of which is often left to the choice of an anesthesiologist. Aim The aim of this study was to compare the analgesic efficacy and safety profile of fentanyl and clonidine as an adjuvant to epidural ropivacaine anesthesia. Setting and Design With institutional ethical committee clearance, a prospective, randomized, placebo-controlled double-blind clinical study was conducted at Vivekananda Polyclinic and Institute of Medical Sciences, Lucknow. Material and Methods Two groups with thirty patients each were randomly allocated to receive 15–20 ml of 0.75% ropivacaine with 75 μg clonidine or 15–20 ml of 0.75% ropivacaine with 75 μg fentanyl, respectively. Block characteristics such as onset of analgesia, maximum level of sensory blockade, complete motor blockade, hemodynamic, time to two-segment regressions, time for rescue analgesia, time to complete motor recovery, and side effects were analyzed. Results Results showed that the onset of blockade is faster when fentanyl is used as additives. Time for two-segment regression was earlier in fentanyl group but time for rescue analgesia was longer in clonidine group. Statistical Analysis Two groups were compared by Student's t-test and Chi-square test; ANOVA and significance of mean difference bet were done by Newman–Keuls test. Conclusion Addition of clonidine to epidural ropivacaine provides superior analgesia than the addition of fentanyl to epidural ropivacaine without much difference in side effect profile.
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What is known and objective: Pruritus is one of the most common adverse effects associated with neuraxial morphine. Ondansetron has been used to deal with the problem of neuraxial morphine-induced pruritus (NMIP). The aim of this meta-analysis was to evaluate the preventive efficacy of ondansetron on NMIP. Methods: Online databases such as PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs). The primary outcome was the incidence of NMIP. We calculated risk ratios (RR) with 95% confidence intervals (CI) for dichotomous data. Trial sequential analysis (TSA) was performed to avoid the risk of making a spurious claim of significant effect and to calculate the sample size necessary to make a robust claim of effect. Results and discussion: Our traditional meta-analysis showed that prophylactic ondansetron could significantly reduce the incidence of NMIP in non-obstetric patients (three trials, RR=0.63, 95% CI 0.45-0.89, P=.008) with modest heterogeneity (I(2) =47%) while it did not show the preventive efficacy of NMIP in obstetric patients (seven trials, RR=0.84, 95% CI 0.69-1.03, P=.10) with obvious heterogeneity (I(2) =82% ). However, TSA demonstrates that more high-quality RCTs are still needed to confirm the preventive efficacy of ondansetron on NMIP in non-obstetric populations and to study whether ondansetron prevents NMIP in obstetric patients. What is new and conclusion: Prophylactic ondansetron can significantly reduce the incidence of NMIP in non-obstetric patients but not in obstetric patients. However, more well-designed trials are still required to test the reliability of the results in our traditional meta-analysis.
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Introduction Opioids are widely used in conjunction with local anesthetics as they permit the use of lower dose of local anesthetics while providing adequate anesthesia and analgesia. It both provides adequate anesthesia as well as lower drug toxicity neuraxial administration of opioids in conjunction with local anesthetics improves the quality of intraoperative analgesia and prolongs the duration of postoperative analgesia. Bupivacaine is the most commonly used drug for subarachnoid block due to its lesser side effects. The present study was conducted to decrease the overall dose of local anesthetics with opioid combination for urological procedure with respect to quality of anesthesia and recovery with patient's satisfaction. Materials and Methods The study population was randomly allocated by computer generated table into two groups; Group A: 5 mg 0.5% bupivacaine + 25 mcg and Group B: 5 mg 0.5% bupivacaine + 25 mg butorphanol. Results Highest level of sensory block was T9 and T8 with the fentanyl group and butorphanol group, respectively. The onset of sensory block was early in fentanyl group than butorphanol group. Duration of both sensory and motor block was significantly higher in butorphanol group. There was no incidence of itching in both groups. There were two patients in fentanyl group and one in butorphanol with hypotension for which injection mephentermine was given. Two patients in fentanyl group complained of nausea and vomiting, for which injection ondansetron was given. One patient complained of pain in fentanyl group for which injection propofol with injection fentanyl was supplemented. Conclusion Low-dose bupivacaine with butorphanol group was devoid of any side effects in the present study but low dose bupivacaine in addition with fentanyl is superior in terms of early postoperative recovery resulting in early discharge and better outcome in comparison to bupivacaine and butorphanol group, which is beneficial in elderly patients with comorbidity.
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The intrathecal space has become an important anatomic site for medical intervention not only in anesthesia practice, but also in many other medical specialties. Undesired/inadvertent intrathecal injections (UII) are generally rare. There is tremendous variation in reported inadvertent administrations via an intrathecal route in the literature, mainly as individual cases and very small case-series reports. This review aims to identify potential sources of UII, its clinical presentations, and appropriate management. The inadvertent injectants are classified as anesthetic agents and pain medicines, chemotherapeutics, radiological contrast agents, antibiotics and corticosteroids, and miscellaneous chemical agents such as tranexamic acid. The clinical effects of UII are dependent upon inadvertent injectant(s) and dose being administered intrathecally, and can range from no adverse effect to profound neurological consequences and/or death. Prompt cerebrospinal fluid (CSF) lavage and cardiopulmonary support seem to be the mainstay of treatment. If serious consequences are anticipated, CSF lavage could be lifesaving. This review additionally provides some options for comprehensive management and preventing strategies.
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The conversion of high-dose intravenous (IV) opioids to an equianalgesic epidural (EP) or intrathecal (IT) dose is a common clinical dilemma for which there is little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1 IT conversion ratio is commonly cited in the literature, especially for morphine. In this study, the authors surveyed 724 pain specialists to elucidate the ratios that respondents apply to convert high-dose IV morphine, hydromorphone, and fentanyl to both EP and IT routes. Eighty-three respondents completed the survey. Conversion ratios were calculated and entered into graphical scatter plots. The data suggest that there is wide variation in how pain specialists convert high-dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most common answer of survey respondent, especially for morphine, though also for hydromorphone and fentanyl. Furthermore, more respondents applied a more aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting less spinal selectivity of those opioids compared with morphine. The authors conclude that there is little consensus on this issue and suggest that in the absence of better data, a conservative approach to opioid conversion between IV and neuraxial routes is warranted.
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Résumé La douleur cancéreuse, de mécanisme souvent mixte, est un problème fréquent, pour lequel un geste chirurgical peut s’avérer utile. Depuis sa naissance, récente, la neurochirurgie s’y est toujours intéressée. Au début du siècle dernier, les insuffisances de la pharmacopée, les progrès des techniques chirurgicales et la révolution pastorienne ont autorisé les premières interventions de chirurgie de la douleur. Nous décrivons les différentes interventions selon un plan à la fois anatomique (de la périphérie vers le centre) et chronologique. Les techniques lésionnelles (rhizotomie postérieure, cordotomie, myélotomie commissurale, tractotomie pédonculaire, tractotomie trigéminale, thalamotomie, gyrectomie, hypophysectomie, cingulotomie, leucotomie préfontale) et non lésionnelles (neurostimulation médullaire, infusion intrathécale et intraventriculaire) sont successivement abordées. L’infusion intrathécale – aujourd’hui privilégiées aux techniques lésionnelles – est d’un apport indéniable dans la prise en charge de ces douleurs, même si l’on regrette que son accès soit inégal.
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Opioids have always been considered the best option in clinical practice for the treatment of severe postoperative pain. However, the spinal administration of an opioid drug does not always guarantee selective action and analgesia in the spine. This fact is due to partial reuptake to blood systemic circulation reaching brain receptors. Recent evidence from clinical studies indicates that bioavailability in the spinal cord biophase is negatively correlated with liposolubility, which is higher for hydrophilic opioids, than for lipophilic ones. Actually, clinical guidelines recommend using a mixture of local anesthetic plus a strong opioid to improve the global analgesic effect, minimize adverse effects and improve the overall patient´s satisfaction. Moreover, an opioid alone like morphine can be administered to provide a long period of postoperative analgesia for 24h, or even 48 h when an extended release epidural formulation is used. In this narrative review, practical information for correct spinal opioid selection is provided to help the physicians a better approach to postoperative multimodal spinal analgesia.
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The history of intrathecal and epidural anaesthesia is in parallel with the development of general anaesthesia. The first published report on opioids for intrathecal anaesthesia belongs to a Romanian surgeon, who presented his experience at Paris in 1901. It was almost a century before the opioids were used for epidural analgesia. Epidural and intrathecal opioids are today part of a routine regimen for intra and postoperative analgesia. Over the last 30 years, the use of epidural opioids has became a standard for analgesia in labor and delivery, and for the management of acute and chronic pain. It has been widely asumed that any opioid placed in the epidural or intrathecal spaces will produce highly selective spinally mediated analgesia that is superior to that produced by other analgesic techniques. Unfortunately, this is simply not true. In fact, multiples opioids are currently employed for spinal use despite the fact that clinical evidence has shown that spinal administration does not produce analgesia with a selective spinal mechanism or the analgesia produced is not superior to that produced by intravenous administration. Appropriate use of spinal opioids necessitates understanding the physiology and clinical pharmacology of these drugs and which opioids produce selective spinal analgesia and which do not. In short, spinal selectivity is greatest for hidrophilic opioids and least for lipophilic opioids. This differences result from inherent differences in the bioavility of opioids at spinal cord opioid receptors. Bioavility differs because lipophilic drugs are more rapidly cleared into plasma than hidrophilic drugs, consequently they produce more early supraspinal side-effects and have a considerably shorter duration of analgesic action. Morphine is probably the most spinally selective opioid currently used in the intrathecal and epidural spaces. Methadone is another opioid that has been shown to have moderate spinal selectivity after epidural administration. However, the long plasma half-life of this opioid results in its acumulation in plasma and greater supraspinal effects over time. Epidural administration of fentanyl offers little or no benefit over the intravenous route except in obstetrics where it does appear to produce modestly selective spinal analgesia. Finally, epidurally administered sufentanil and alfentanil appear to produce analgesia by systemic uptake and redistribution to brainstem opioid receptors.
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Osseous anatomy The spinal column consists of both the vertebral column and the spinal cord. It comprises 33 vertebrae (Table 56.1) and has characteristic curves in the lumbar and thoracic regions, which give it a “double S” shape (Fig. 56.1). A lordosis is an anteriorly convex curve, seen in the cervical and lumbar region, and kyphosis is a posteriorly convex curve, seen in the thoracic and sacral sections of the spinal column. The natural curves of the spinal column may influence the spread of medications injected in the subarachnoid space. The bony vertebral column fulfills several functions (Table 56.2). Vertebral arch and body Each vertebra has an anterior part or body and a posterior part or vertebral arch (Fig. 56.2). The vertebral arch has two pedicles and two laminae, and together they enclose a foramen, the vertebral foramen All the vertebral foramina constitute the spinal canal, which houses the spinal cord and nerve roots. Each vertebral arch supports seven processes: One spinous process, a midline structure arising between the two laminae, a place for attachment of muscles and ligaments. Two transverse processes, laterally at the junction of the laminae and the pedicles. Four articular processes - two superior, projecting upward, and two inferior, projecting downward - that participate in each zygapophyseal joint above and below. The pedicles of two adjacent vertebrae form the intervertebral foramina on each side, through which nerve roots exit the spinal column.
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Introduction Neuraxial anesthesia is the term used to describe both intrathecal (spinal) and epidural nerve blocks. Drugs delivered into the epidural space do not behave as drugs in the intrathecal space. Understanding the differences allows the anesthesiologist to choose which space to deliver a drug based on the benefits of each (Table 58.1). The epidural space is located within the spinal canal but lies outside the dural sac. Anesthetics delivered into this space may provide regional surgical anesthesia, prolonged postoperative analgesia, or treat chronic pain syndromes. Successful epidural anesthesia depends on proper patient selection, knowledge of the surgery, its location and duration, excellent three-dimensional appreciation of the neuraxial anatomy, and appropriate choice of anesthetic agent. This chapter focuses on these factors and also describes the complications associated with epidural anesthesia. Anatomy Appreciation of the bony spinal anatomy, the ligaments connecting these bones, and the contents and borders of the epidural space itself is important for the safe and expeditious performance of epidural blocks. For a detailed description of the spinal bony and ligamentous anatomy, please refer to Chapter 56.
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One of the most important surgeons of the 1900 period was the Romanian-born Thomas Jonnesco. He became a surgeon in Paris (1885-1890) under the guidance of D.M. Bourneville and J. Peyrot (Bicetre), P. Berger (Tenon), A. Le Dentu (St. Louis) and A. Verneuil (Pitié-Salpětrière). In 1894, he gained at the Paris Faculty of Medicine the title of professor of anatomy. In the same year he was selected by the professors Poirier, Charpy and Nicolas to be their collaborator in a treatise of anatomy, published in 1894. In 1895, he returned to Bucharest to lead the Institute of Topographic Anatomy and Experimental Surgery, especially created for him. He also accepted the Chair of the Clinical Surgery of Coltzea Hospital in Bucharest. In 1896 he founded in Paris the French periodical "Archives des Sciences Médicales". Jonnesco was a prolific surgeon in the field of experimental surgery, especially cervical sympathectomy, general spinal anaesthesia but also in surgical oncology and genito-urinary field. He also drew clinical correlations on surgical techniques of gastrectomy for cancer, on total abdominal genital ablation as treatment for septic conditions of the uterus and the adnexa or on the large abdominal hysterectomy with complete ilio-lumbo-pelvic lymph node dissection in uterine cancer, which refined Wertheim's hysterectomy method. Thomas Jonnesco is now considered the founder of the modern Romanian school of surgery.
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Two groups of patients were allowed to self-administer morphine (n = 17) or pethidine (n = 15) extradurally after abdominal surgery, for a mean period of 16 h. Bolus increments of morphine 1 mg or pethidine 20 mg were administered by programmable pump. Pain relief from extradural patient-controlled analgesia (PCA) was excellent in all but two patients in the morphine group. Pain relief was not qualitatively different between the two groups. No clinical respiratory depression was seen. The average consumption of extradural morphine was 0.52 ± 0.29 mg h−1 (range 0.19–1.04 mg h−1) and of pethidine 18.0±8.1 mg h−1 (5.8–35.4 mg h−1). This yields an equianalgesic dose relationship of 1:35. Morphine consumption was more irregular than pethidine consumption. Morphine and pethidine plasma concentrations measured during PCA were well below the reported minimum analgesic plasma concentrations in most cases. Several patients, particularly in the pethidine group, tended to increase their opioid consumption during PCA. This could be explained by an increasingly smaller fraction of the pethidine bolus being absorbed to the subarach-noid space during frequent repetitive dosing. The large inter-individual variation in consumption makes it impossible to recommend a standard dose of extradural morphine or pethidine for analgesia of predictable duration and with a minimum of adverse effects.
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The Swedish Society of Anaesthetists conducted a nationwide retrospective survey of clinical experience with extradural and intrathecal opiates Special interest was focused on the frequency and type of ventilatory depression. The questionnaire was answered by 84 of 93 departments (90%). Up to May 1981 extradural morphine had been given to approximately 6000–9150 patients, extradural pethidine to 220–450 and intrathecal morphine to 90–150 patients Ventilatory depression requiring treatment with naloxone was reported in 23 patients treated with extradural morphine (0.25–0.40%) and in six given uitrathecal morphine (4–7%). In 22 patients the administration of extradural morphine was considered as a major contributory factor for the occurrence of ventilatory depression Only two of these 22 patients experienced ventilatory depression later than 6 h after the last dose of opiates (s.c, i.m.,i.v., or extradural). Patients aged 70 yr or more, those receiving thoracic extradural puncture and those with reduced ventilatory capacity seemed to be oyerrepresented
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Epidural injections of 2 mg morphine were given to 10 patients with severe acute or chronic pain. All cases had considerable amelioration of pain, which commenced within 2-3 min, reached a peak in 10-15 min, and was effective for 6-24 h. It is suggested that the morphine reached the subarachnoid space and produced its effect by direct action on the specific opiate receptors in the substantia gelatinosa of the posterior-horn cells of the spinal cord.
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The authors present their experience about spinal anesthesia with pethidine as the sole medication.713 patients whose mean age was 56.5 years received 1 mg · kg−1 of pethidine in 50 p. 100 aqueous solution administred by subarachnoïd route. Indications were surgical procedures involving upper and lower abdomen, perineum and lower limbs.The set up of anesthesia is quite similar to those obtained with local anesthetics. Sensitivity disappears during the fisrst three minutes in the area below the puncture site and in the following two or three minutes areflexia and paralysis in noted. The duration of the motor and sensory block is 90 to 120 minutes. Recovery appears to be in a reverse order.Spinal anaesthesia with pethidine exhibit the following characteristics :--sensory and motor blockade with minimal adverse reactions giving good and very good results in more than 90 per cent of cases, when involving perineum and lower limbs;--the most frequent adverse effect is a syndrome including hypotension, bradycardia and hypoxemia, appearing 20 to 30 minutes after injection, reversal is easily obtained by administration of pressure drugs and artificial ventilation. Neither delayed respiratory depression nor neurologic damage were noted;--a long lasting post-operative analgesia.In conclusion, this work demonstrate that :--1 mg · kg−1 of pethidine administred by subdural route realize a complete spinal anesthesia including motor, sensory and sympathetic blockade allowing surgical procedures in good conditions of security;--increasing the dosage of pethidine over 1 mg · kg−1 is not wise in order to avoid the occurrence of adverse side effects such hypotension, bradycardia and bradypnaea;--this technic is only indicaded for surgery in perineum and lower limbs.
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The work of Aburel has only really been known in France and countries of French culture. In 1948, when the introduction of continuous caudal analgesia in obstetrics was attributed to Hingson, Professor Pierre Lantejoul of Tarnier Hospital, Paris, invited Aburel to France through the French Ministry of Foreign Affairs to deliver a series of lectures, and also to write a monograph, to defend his 'evident paternity' of the method. It seems that Aburel was unable to honour this invitation, as in the same way, 24 years later, he was unable to answer letters written to him by Hingson. The freezing of cultural and scientific relations and contacts between East and West after the second world war, and publication of his papers in only French and Rumanian medical journals, many of them of general interest, or in doctoral theses, explain why Aburel's pioneer work in the development of regional techniques for pain relief in childbirth remain unknown in other countries of the world. This paper is an attempt to record in an authoritative fashion the name, the dedicated life and the work of an unknown doctor, whom experts such as Hingson and Cleland consider a 'friend', 'pioneer' and 'benefactor of mankind'.
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Epidural injections of a 2 mg morphine were given to 10 patients with severe acute or chronic pain. All cases had considerable amelioration of pain, which commenced within 2-3 min, reached a peak in 10-15 min, and was effective for 6-24 h. It is suggested that the morphine reached the subarachnoid space and produced its effect by direct action on the specific opiate receptors in the substantia gelatinosa of the posterior-horn cells of the spinal cord.
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Eight patients who had severe intractable pain in the back and legs secondary to malignancies of the genitourinary tract with invasion of the lumbosacral plexus were selected for study. Two of the eight patients reported complete relief of pain after separate injections of morphine and physiologic saline solution, although the mean duration of relief after morphine injection was 15 hours, whereas that after injection of physiologic saline solution was seven hours. The other six patients reported complete relief from pain after the morphine injections. Relief lasted 12 to 24 hours, the average duration being 20 hours. Elapsed times from instillation of the drug to its maximal effect ranged from about 15 to 45 min. Increasing the dose of morphine to 1.0 mg did not prolong the relief proportionately. In contrast to the good response to morphine, there was no improvement after nine injections of physiologic saline solution. The results of repeated injections of either morphine or physiologic saline solution in the same patient were strikingly reproducible.
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1. Radiant-heat stimuli of different intensities were delivered every 28 s to the thenar eminence of the hand of human subjects and to the receptive fields (RFs) of 58 "mechanothermal nociceptive" and 16 "warm" C-fibers, most of which innervated the glabrous skin of the monkey hand. A CO2 infrared laser under control via a radiometer provided a step increase in skin temperature to a level maintained within +/- 0.1 degrees C over a 7.5-mm-diameter spot. 2. Human subjects categorized the magnitude of warmth and pain sensations evoked by stimuli that ranged in temperature from 40 to 50 degrees C. The scale of subjective thermal intensity constructed from these category estimates showed a monotonically increasing relation between stimulus temperature and the magnitude of warmth and pain sensations. 3. The mechanothermal fibers had a mean RF size of 18.9 +/- 3.2 mm2 (SE), a mean conduction velocity of 0.8 +/- 0.1 m/s, mean thresholds of 43.6 +/- 0.6 degrees C for radiant heat and 5.95 +/- 0.59 bars for mechanical stimulation, and no spontaneous activity. In contrast, warm fibers had punctate RFs, a mean conduction velocity of 1.1 +/- 0.1 m/s, heat thresholds of less than 1 degrees C above skin temperature, no response to mechanical stimulation, and a resting level of activity in warm skin that was suppressed by cooling. 4. The cumulative number of impulses evoked during each stimulation in the nociceptive afferents increased monotonically as a function of stimulus temperature over the range described by humans as increasingly painful (45-50 degrees C). Nociceptive fibers showed little or no response to stimulus temperatures less than 45 degrees C that elicited in humans sensations primarily of warmth but not pain. In contrast, the cumulative impulse count during stimulation of each warm fiber increased monotonically with stimulus temperature over the range of 39-43 degrees C. However, for stimuli of 41-49 degrees C the cumulative impulse count in warm fibers was nonmonotonic with stimulus temperature. Warm-fiber response to stimuli of 45 degrees C or greater usually consisted of a short burst of impulses followed by cessation of activity. 5. The subjective magnitude of warmth and pain sensations in humans and the cumulative impulse count evoked by each stimulus in warm and nociceptive afferents varied inversely with the number, delivery rate, and intensity of preceding stimulations. 6. The results of these experiments suggest the following: a) that activity in the mechanothermal nociceptive C-fibers signals the occurrence of pain evoked by radiant heat, and that the frequency of discharge in these fibers may encode the intensity of painful stimulation; b) that activity in warm fibers may encode the intensity of warmth at lower stimulus temperatures, but is unlikely to provide a peripheral mechanism for encoding the intensity of painful stimulation at higher stimulus temperatures.
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Narcotic analgetics administered directly into the spinal subarachnoid space of the rat via a chronically inserted catheter produce a potent analgesia that can be antagonized by naloxone. The narcotics, acting only at the spinal level, changed cord function to block not only spinal reflexes but also the operant response to painful stimuli.
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When opiates are administered by the epidural and spinal routes, itching occurs as a side effect. We reviewed 52 reports in the literature of the use of epidural and spinal opiates to assess the incidence of itching and found an overall incidence of 8.5% in patients receiving epidural opiates, and 46% in patients receiving spinal opiates. The symptom is a recognised, though rare, side effect of systemically administered opiates, and in the case of systemic administration the itching is generalised. In the case of epidural and spinal administration, the itching may be generalised. But often a segmental distribution is demonstrable, centred on the level of injection, or the itching is localised to a particular area such as the nose and face. It is likely therefore, in the latter case, that there is an effect upon the spinal cord itself. Although occasionally spinal opiate-induced itching is extremely troublesome and lessens the value of spinal opiate pain relief, in the majority of cases, the itching is not severe and is treatable with naloxone. However, the frequent occurrence of the symptom and the likelihood of a spinal cord mechanism do provide valuable information about opioid actions, and benefit may be derived from better understanding the phenomenon. This paper states a hypothesis to explain spinal opiate-induced itch and explores the possible mechanisms of the effect.
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To test the effectiveness of adrenergic agonists in correcting the vascular sequelae of spinal anesthesia, we used venous reservoir volume (RV) and mean arterial pressure (MAP) as indices of the changes in venous capacitance and arterial resistance produced by adrenergic agonists in dogs anesthetized with pentobarbital and undergoing cardiopulmonary bypass (CPB). A CPB-based technique was chosen both to prevent drug and reflex effects on the heart from influencing the results and to provide a convenient means by which to monitor venous capacitance. Total spinal anesthesia significantly decreased both RV and MAP relative to steady-state CPB values. Return of these hemodynamic alterations to baseline was attempted using pure alpha- and beta-adrenergic agonists, and a mixed adrenergic agonist (phenylephrine, isoproterenol, and ephedrine, respectively). Isoproterenol increased RV, but further decreased MAP. Phenylephrine increased MAP but not RV. Ephedrine increased both MAP and RV. We conclude that a mixed adrenergic agonist such as ephedrine more ideally corrects the noncardiac circulatory sequelae of spinal anesthesia than does either a pure alpha- or beta-adrenergic agonist.
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Tritiated naloxone, a powerful opiate antagonist, specifically binds to an opiate receptor of mammalian brain and guinea pig intestine. Competition for the opiate receptor by various opiates and their antagonists closely parallels their pharmacological potency. The opiate receptor is confined to nervous tissue.
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A METHOD IS DESCRIBED FOR ANALYZING THE ASSOCIATION OF THE OPIATE NARCOTIC LEVORPHANOL WITH BRAIN TISSUE INTO THREE COMPONENTS: nonsaturable, saturable nonspecific, and saturable stereospecific. The method may be of general applicability for the study of the interaction of drugs with body tissues. In mouse brain the stereospecific binding of levorphanol represents only 2% of the total association of drug with tissue, and it was found only in certain membrane fractions. The material responsible for the stereospecific binding might be the opiate receptor.
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Experience in 1200 patients of the side-effects of epidural morphine chloride (2 mg in 10 ml of normal saline) for postoperative pain relief is reported in the first 242 patients a commercial preparation containing sodium-pyrosulphite 0.1 mg and sodium-EDTA 0.1 mg per 10 mg morphine chloride was used. The remaining 958 patients were treated with a preservative-free, filtered solution. The side-effects regarded as related to epidural morphine were: Nausea or vomiting, 204 (17%); blood pressure drop (≥20 mm Hg), 24 (2%); itching (first 242 patients), 36 (15%); itching (next 958 patients), 9 (1%); urinary retention, 181 (15%); respiratory depression, 1.
Article
The pharmacology of the antinociceptive effects of opiates with an action limited to the spinal cord was studied in primates by examining the effects of opioid peptides and alkaloids administered through chronically implanted intrathecal catheters on the discrete trial shock titration threshold. In these experiments, dose-response curves were obtained and the potencies of these several agents were: lofentanyl > metkephamid > β-endorphin > [D-Ala2-Met5]enkephalin amide > [D-Ala2-D-Leu5]enkephalin (DADL) > [D-Ala2-Met5]enkephalin > morphine > l-methadone > meperidine >> d-methadone = 0. The time of onset and the duration of action were closely correlated with the lipid partition coefficient of the drug. Dose-response curves for inhibiting the intrathecal effects of DADL, metkephamid and morphine were obtained with systemically administered naloxone. An analysis of the data, providing an apparent pA2 value for naloxone against morphine, metkephamid and DADL, gave pA2 values of 6.9, 6.4 and 6.1, respectively. The calculated slopes of the derived Schild plots did not significantly differ from -1. Daily intrathecal administration of doses of morphine displayed a loss of responsiveness over a 5- to 9-day period. Opiate-free intervals of 7 days resulted in a significant recovery of opiate sensitivity. Animals rendered tolerant in this fashion to morphine showed a similar loss of responsiveness to β-endorphin but no loss of sensitivity to DADL or to metkephamid. In contrast, animals rendered tolerant to metkephamid showed a significant reduction in the responsiveness to otherwise active doses of DADL, morphine and β-endorphin. The differential structure-activity relationship, the presence of different pA2 values for DADL, metkephamid, morphine and β-endorphin and the failure to find cross-tolerance between DADL and metkephamid in morphine-tolerant animals, clearly suggest the possibility of two receptor populations for which morphine and DADL may be thought to be prototypical agonists. The similarity of these results with the findings made in the guinea-pig ileum and mouse vas deferens support the concept of two subpopulations of receptors which have been classified in the guinea-pig ileum and mouse vas deferens as being mu and delta, respectively. These results do not exclude the possibility of other subpopulations of naloxone-sensitive receptors associated with antinociception in the spinal cord or that these populations are in fact homogeneous. They do, however, clearly suggest a differentiation in the subpopulation of receptors mediating antinociception at the spinal cord level.
Article
In a clinical, double-blind study including 45 patients, who all underwent lower abdominal or urological surgery, the analgesic effect, latency and duration of epidural application of morphine were investigated in doses of 2 and 4 mg, respectively, compared to placebo. No significant difference was found in the effect of 2 mg morphine, compared to placebo. A significant decrease in pain score was found in the group of patients who received 4 mg morphine administered epidurally; however, this effect did not occur until 60 min after epidural administration. The effect of 4 mg morphine was found to be of long duration, as eight out of 15 patients did not require any supplementary analgesics within the first 24 h, compared to two out of 14 and three out of 15 patients, respectively, in the placebo and 2-mg groups.
Article
The authors evaluated intrathecal morphine given at the same time as a spinal anesthetic for postoperative analgesia. Five patients undergoing elective surgical procedures, ages ranging from 20 to 77 yr, consented to the procedure. Approximately ten hours after administration of the spinal anesthetic, three patients (aged 20, 60, and 77 yr) experienced bradycardia, decreased respiratory rate, and pinpoint pupils. Two patients subsequently had respiratory arrest, which responded to naloxone given intravenously. It is felt that intrathecal narcotics may have a role in postoperative analgesia. However, the dose needed to produce analgesia without also causing undesirable side effects has yet to be established.
Article
The new methods of intrathecal and epidural administration of opiates are of great interest, but perhaps it has not been sufficiently emphasised that this treatment should probably be reserved for short-lasting pain, due to the rapid exhaustion of its efficacy after repeated doses. Our initial study was conducted on 19 subjects divided into two groups (those using intrathecal morphine, and controls (morphine and/or pentazocine either intramuscular or intravenous). These results demonstrated the greater efficacy, in 24 hours, of a single intrathecal dose of 0.5 mg of morphine with respect to a repeated analgesic dose 40 times greater of the same drug and/or pentazocine administered either intramuscularly or intravenously. There were no circulatory or respiratory side-effects.
Article
In 12 consecutive unselected patients admitted to a consultant maternity unit one single injection of subarachnoid morphine sulphate 1.5 mg abolished pain during the first stage of labour. Pain in the second stage was abolished in four patients and lessened in three. During the early puerperium, pain at the site of the episitotomy was much reduced. Side effects included itching of the face, nausea and vomiting, and frontal headache, but these were mild and simply treated. They were even less severe in the last four patients, in whom barbotage was not used in administering the morphine. The high rate of forceps delivery and caesarean section (three cases of each) was not thought to be associated with the use of intrathecal morphine. These findings show that intrathecal morphine can abolish the pain of labour, whether spontaneous or induced, while preserving the mother's full awareness of labour and her co-operation in the second and third stages of labour. Further, controlled, trials are warranted.
Article
Ten healthy males between 18 and 33 years received 10 mg morphine sulfate intravenously, or by lumbar epidural injection at two sessions 2-4 weeks apart, in random sequence. The following observations were made at intervals for 22 h. (1) Segmental hypalgesia to ice and pin scratch. (2) Cold pressor response test in hand and foot as an index of analgesia. (3) Time of onset and duration of side effects. (4) Serum concentrations of morphine. Few non-respiratory changes were seen after intravenous morphine. Cold pressor response was unchanged in hand and foot, no segmental hypalgesia or itching occurred, and only one subject complained of nausea. Marked changes occurred after epidural morphine. Cutaneous hypalgesia to ice and pin scratch appeared in the thoracolumbar region all subjects. In six subjects hypalgesia rose to the midthoracic region during the second or third hour and to the trigeminal distribution between the sixth and ninth hour in five subjects. Cold pressor response fell rapidly in the foot during the first 1.5 h after epidural morphine, and a little later cold pressor response also fell in the hand in all subjects, and remained depressed for the duration of the experimental period. Pruritus occurred at three hours in nine of the 10 subjects, nausea at about four hours in six of the subjects, and vomiting at about six hours in five of the subjects. Hypalgesia and side effects were not related to serum concentrations of morphine. These results suggest that lumbar epidural morphine travels cephalad in the cerebrospinal fluid to reach the brain stem and fourth ventricle by the sixth hour.
Article
The authors present their experience about spinal anesthesia with pethidine as the sole medication. 713 patients whose mean age was 56.5 years received 1 mg . kg-1 of pethidine in 50 p. 100 aqueous solution administered by subarachnoid route. Indications were surgical procedures involving upper and lower abdomen, perineum and lower limbs. The set up of anesthesia is quite similar to those obtained with local anesthetics. Sensitivity disappears during the first three minutes in the area below the puncture site and in the following two or three minutes areflexia and paralysis is noted. The duration of the motor and sensory block is 90 to 120 minutes. Recovery appears to be in a reverse order. Spinal anaesthesia with pethidine exhibit the following characteristics: --sensory and motor blockade with minimal adverse reactions giving good and very good results in more than 90 per cent of cases, when involving perineum and lower limbs; --the most frequent adverse effect is a syndrome including hypotension, bradycardia and hypoxemia, appearing 20 to 30 minutes after injection, reversal is easily obtained by administration of pressure drugs and artificial ventilation. Neither delayed respiratory depression nor neurologic damage were noted; --a long lasting post-operative analgesia. In conclusion, this work demonstrates that: --1 mg . kg-1 of pethidine administered by subdural route realize a complete spinal anesthesia including motor, sensory and sympathetic blockade allowing surgical procedures in good conditions of security; --increasing the dosage of pethidine over 1 mg . kg-1 is not wise in order to avoid the occurrence of adverse side effects such as hypotension, bradycardia and bradypnaea; --this technic is only indicated for surgery in perineum and lower limbs.
Article
Thirty-three patients were randomly assigned to two groups to study the analgesic potency, duration of action and side effects of epidural and intramuscular morphine after hip surgery. Two milligrams of preservative-free morphine chloride in 10 ml of normal saline in the epidural space was compared to 10 mg of intramuscularly administered morphine. There was a more rapid onset of action after intramuscular morphine. However, the quality of pain relief was substantially higher and the duration of action markedly longer after epidural morphine. The total dose required in the epidural group was 3.6 mg and in the intramuscular group 41 mg during the 15-h observation period. The side effects of epidural morphine were few and mild, the most embarrassing being urinary retention (20%). Nausea and/or vomiting was less common after epidural morphine (20% versus 55%). Pruritus or respiratory depression which have been reported previously were not encountered. However, it is recommended that preservative-free solution are used to avoid itching and that the patients are monitored, as respiratory depression may occur long after administration of epidural opiate.
Article
A 31-year-old woman had an elective Caesarean section under combined spinal/epidural anaesthesia. At the end of the operation, diamorphine 2.5 mg in 5 ml of 0.25% bupivacaine plain was injected through the epidural catheter. Forty minutes after this, the patient had a cardiorespiratory arrest in an ordinary postnatal ward.
  • Wang
  • Butterworth
  • Edwards