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Sex differences have been ascribed mainly to hormonal and life-span factors, while neglecting chromosomal and socio-cultural determinants. Science is now reviewing the disregard for sex and gender as a potential explanation for the lack of expected outcomes in whole populations from clinical research. The medical research process begins with a hypothesis that is applied, generating results that can be disseminated. Many factors impact on this process that can be ascribed to sex, as a biological construct, and gender, as a psychosocial process involving experimental subjects, research- ers, funders and the public. Drug trial data analysis and publication of data from women and men have recently been scrutinized and found lacking, because expected clinical outcomes from ‘evidence-based’ guidelines are not being achieved. Hence visibility of sex and gender in all aspects of medical research is considered essential if personalized therapies are to bring benefits to both men and women.

Based on the neurophysiology of dyspnoea and the distribution of cannabinoid receptors within the central nervous system, we hypothesize that the unpleasantness of breathlessness will be ameliorated in humans by cannabinoids, without respiratory depression. Five normal and four chronic obstructive pulmonary disease (COPD) subjects entered a double blind, randomized, placebo-controlled crossover study with two test days. Subjects received sublingual cannabis extract or placebo. A maximum of 10.8 mg tetrahydrocannabinol and 10 mg cannabidiol were given. Breathlessness was simulated using fixed carbon dioxide loads. Measurements taken were of breathlessness (visual analogue scale [VAS] and breathlessness descriptors), mood and activation, end-tidal carbon dioxide tension and ventilatory parameters. These were measured at baseline and 2 hours post placebo and drug administration. Normal and COPD subjects showed no differences in breathlessness VAS scores and respiratory measurements before and after placebo or drug. After drug administration, COPD subjects picked ‘air hunger’ breathlessness descriptors less frequently compared to placebo. We have shown that breathlessness descriptors may detect an amelioration of the unpleasantness of breathlessness by cannabinoids without a change in conventional breathlessness ratings (VAS). A stimulus more specific for air hunger may be needed to demonstrate directly a drug effect on breathlessness. However, this study shows that the inclusion of respiratory descriptors may contribute to the assessment of drug effects on breathlessness.

Purpose Adverse drug reactions (ADRs) to local anaesthetic drugs are reported voluntarily through the Adverse Drug Reporting On Line Tracking system (ADROIT). We aimed to determine hazards associated with drugs commonly used in anaesthesia including ropivacaine and levobupivacaine. Methods The ADROIT database was queried for all ADRs to local anaesthetics used in anaesthesia and surgery between 1967 and 2005. Details of age, sex, suspect drug, date and reaction details were analysed. Results There were 985 reports analysed, 797 for lidocaine, 160 for bupivacaine, 16 for ropivacaine and 12 for levobupivacaine. The female to male ratio was 1.6:1 and age was not a factor determining the frequency of reactions. A vasoconstrictor was included in the lidocaine formulation in 27% of reports. When methylprednisolone (Depo-Medrone®) or prilocaine (as EMLA™ cream) were used in combination with lidocaine, the frequency of allergic reports increased significantly (p

Factors that influenced the choice of dose of oral transmucosal fentanyl at the time of burns dressing change were investigated in a prospective study. After Ethics committee approval, data was analysed from 29 consecutive patients who had been recruited and consented for a study of pain associated with burns dressings. Patients had completed an 11-point verbal pain intensity score (VRS) prior to and after the dressing change. Analgesic use during for this period was documented. Doses of 600 to 1200 mcg of transmucosal fentanyl (Actiq ® ) were given based on individual assessment. The pre-dressing VRS (median [range]) in the 15 patients who received 600 mcg was 8 [3–10] and was higher than the VRS of 6 [2–9] in the 800–1200 mcg group. The time since the burn was longer in the low dose group at 7 [1–22] days compared with 5 [0–50] days in the higher dose group. In addition 73% of the low dose group was prescribed opioids regularly prior to the dressing compared with 57% of the high dose group. The choice of a lower transmucosal fentanyl dose was based on prior use of opioids and the age of the burn rather than on the patient's pain intensity.

Summary Objectives A shortfall exists of female doctors in senior academic posts in the United Kingdom. Career progression depends on measures of esteem, including publication in prestigious journals. This study investigates gender differences in first and senior authorship in six peer-reviewed British journals and factors that are associated with publication rates. Design and main outcome measures Data was collected on United Kingdom first and senior authors who had published in the British Medical Journal, Lancet, British Journal of Surgery, Gut, British Journal of Obstetrics and Gynaecology and the Archives of Diseases in Childhood. Authorship and gender were quantified for 1970, 1980, 1990, 2000 and 2004 ( n=6457). In addition, selected questions from the Athena Survey of Science Engineering and Technology (ASSET2006), web-based doctor's self-report of publications were also analysed ( n=1162). Results Female first authors increased from 10.5% in 1970 to 36.5% in 2004 (pConclusion The increase in UK female first authors is encouraging. In contrast, there is considerable lag and in some specialties a decline in female senior authors. Factors that could narrow the gender gap in authorship should be sought and addressed.

Subtle genetic and psychological variations are Increasingly recognized to contribute to pain and analgesic efficacy and safety. The influence of sex on this relationship remains poorly understood, particularly in humans. The issue is complicated by the overlay of gender onto physical sex, and its associated stereotypes and expectations. Women appear to use more pain-relieving medications than men; however, it remains unclear whether these observations represent true differences in analgesic usage patterns, or reporting bias. Differences in analgesic efficacy relating to body composition, metabolism and hormonal profiles have been demonstrated. Psychological and social elements of gender have also been associated with altered pain experiences and analgesic use profiles, albeit with significant individual variations. Intra-group differences may ultimately prove more important than sex differences. Further research may unravel the various threads linking gender and sex effects on analgesia with the aim of individualizing analgesia to optimize pain relief.

In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?"

Background Women are often unprepared for emergency obstetric procedures and need to receive information about anaesthesia quickly and succinctly. In the absence of previous studies, we sought feedback from women to find out how information was given, and particular areas of concern in order to define practice and improve women’s experiences. Methods After Ethics Committee approval this prospective structured questionnaire study was conducted in a teaching and a district general hospital. Women were recruited up to 48 h after anaesthesia. Results Of 102 women studied, 55 had no prior knowledge of obstetric anaesthetic interventions and risks until told, usually by the obstetrician (n = 47), just before the procedure. The most frightening aspect was anticipating the efficacy of regional anaesthesia (n = 18), but 28 women were reassured by the explanation provided by the anaesthetist. All but two women expressed satisfaction with the content of information and the described attendant risks. Nevertheless, in contrast to our observed practice, 51 (50%) would have preferred having verbal information before labour preferably from an anaesthetist or midwife. Conclusions Most women were unprepared for emergency obstetric anaesthesia. Many received information just before the event. After delivery they expressed a clear preference for earlier information.

Background: The research process from study design and selecting a species and its husbandry, through the experiment, analysis, peer review, and publication is rarely subject to questions about sex or gender differences in mainstream life sciences research. However, the impact of sex and gender on these processes is important in explaining biological variations and presentation of symptoms and diseases. Objective: This review aims to challenge assumptions and to develop opportunities to mainstream sex and gender in basic scientific research. Methods: Questions about the mechanisms of sex and gender effects were reviewed in relation to biological, environmental, social, and psychological interactions. Gender variations, in respect to aging, socializing, and reproduction, that are present in human populations but are rarely featured in laboratory research were considered to more effectively translate animal research into clinical health care. Results: Methodologic approaches to address the present lack of a gender dimension in research include actively reducing variations through attention to physical factors, biological rhythms, and experimental design. In addition, through genomic and acute nongenomic activity, hormones may compound effects through multiple small sex differences that occur during the course of an acute pathologic event. Furthermore, the many exogenous sex steroid hormones and their congeners used in medicine (eg, in contraception and cancer therapies) may add to these effects. Conclusions: The studies reviewed provide evidence that sex and gender are determinants of many outcomes in life science research. To embed the gender dimension into basic scientific research, a broad approach gender mainstreaming is warranted. One example is the use of review boards (eg, animal ethical review boards and journal peer-review boards) in which gender-related standardized questions can be asked about study design and analysis. A more fundamental approach is to question the relevance of present-day laboratory models to design methods to best represent the age-related changes, comorbidity, and variations experienced by each sex in clinical medicine.

Background Sevoflurane has favourable physical qualities for inhaled analgesia during labour pain. The aim of this preliminary study was to identify its optimum concentration. Methods In this open-labelled escalating-dose study, 22 parturients in labour self-administered sevoflurane at 10 contractions using an Oxford Miniature Vaporiser. The inspired concentration was increased by 0.2% after each contraction from 0% to 1.4% or decreased if sedation occurred. Visual analogue scores (0–100 mm) for pain intensity, pain relief, sedation, mood and coping were measured after each contraction. Results The median (IQR [range]) pain relief and sedation scores increased from 44 (43–56 [4–93]) mm and 55 (43–56 [0–98]) mm at 0.2% sevoflurane, to 74 (72–78 [50–80]) mm and 71 (71–73 [33–97]) mm at 1.2% sevoflurane, respectively. Pain relief scores did not show any significant increase above 0.8% whilst sedation continued to increase, with excessive sedation occurring at 1.2% sevoflurane. No significant changes in other scores were measured. Conclusions We concluded that the optimal sevoflurane concentration in labour was 0.8%. This concentration allows a safety margin and balances the risk of sedation with the benefit of pain relief in labour.

Purpose Anaesthetic drugs were selected from the Medicines and Healthcare products Regulatory Agency Drug Analysis Prints in order to determine the number and types of reported reactions and associated mortality. Methods The chosen drug groups were the intravenous induction agents, the neuromuscular blocking drugs and neostigmine, the inhalational anaesthetic agents and nitrous oxide, local anaesthetic agents and a selection of analgesics agents, naloxone and midazolam and its antagonist flumazenil. From each drug file, the number and type of reactions were analysed. Mortality was calculated as a percentage of the number of deaths against patient reports. Results A total of 11 199 reactions were analysed from 6603 patients of whom 620 (9%) died. Few drug records reported reactions from multiple constituent formulations. The majority of reactions were not allergic. The highest mortality was in the inhalational anaesthetic group. Although the greatest number of fatal events was associated with halothane, this drug is no longer used. Nevertheless the percentage remains high because cardiovascular mortality is still being reported. Local anaesthetic use was associated with the smallest percentage mortality (3%). The highest reported number of reactions was associated with the intravenous induction agents and idiosyncratic neurological and peripheral vascular reactions were linked with the use of etomidate. Conclusions The reporting of allergic reactions was low. The data demonstrate that induction of anaesthesia presents the highest risk of adverse drug reaction; there is also mortality from newer drugs for example, desflurane, remifentanil as well as from drugs for which there is no alternative, for example, suxamethonium. Copyright © 2006 John Wiley & Sons, Ltd.

Background Cannabinoids have dose-related antinociceptive effects in animals. This clinical study aimed to investigate whether a single oral dose of cannabis plant extract (Cannador; Institute for Clinical Research, IKF, Berlin, Germany) could provide pain relief with minimal side effects for postoperative pain. Methods Patients (aged 18-75 yr) were recruited and consented before surgery if patient-controlled analgesia was planned for provision of postoperative pain relief. Each patient received a single dose of 5, 10, or 15 mg Cannador if he or she had at least moderate pain after stopping patient-controlled analgesia. Starting with 5 mg, dose escalation was based on the number of patients requesting rescue analgesia and adverse effects. Pain relief, pain intensity, and side effects were recorded over 6 h and analyzed using tests for trend with dose. Results Rescue analgesia was requested by all 11 patients (100%) receiving 5 mg, 15 of 30 patient (50%) receiving 10 mg, and 6 of 24 patients (25%) receiving 15 mg Cannador (log rank test for trend in time to rescue analgesia with dose P < 0.001). There were also significant trends across the escalating dose groups for decreasing pain intensity at rest (P = 0.01), increasing sedation (P = 0.03), and more adverse events (P = 0.002). The number needed to treat to prevent one rescue analgesia request for the 10-mg and 15-mg doses, relative to 5 mg, were 2.0 (95% confidence interval, 1.5-3.1) and 1.3 (95% confidence interval, 1.1-1.7), respectively. The study was terminated because of a serious vasovagal adverse event in a patient receiving 15 mg. Conclusion These significant dose-related improvements in rescue analgesia requirements in the 10 mg and 15 mg groups provide a number needed to treat that is equivalent to many routinely used analgesics without frequent adverse effects.

Summary The handover of patient information between shifts enables continuity of care and increases patient safety. We surveyed UK practice during handovers in obstetric anaesthesia. A questionnaire was sent to 239 lead consultant obstetric anaesthetists to record routine practice in their unit and individual opinion about handover procedures. Responses were received from 168 anaesthetists, a 70% response rate. Handover policies were available in 10% of units. Most (76%) responding units had an allocated time for handover. In most units (76%), the duration of handover was reported as being

Summary Cannabinoids are increasingly being considered for the management of various painful conditions, and could be considered as an option for treating acute pain in sickle cell disease (SCD). The objective of this study was to determine the extent of use of cannabis in the community for pain and other symptom relief, and its side effects during self-administration in patients with SCD. Patients attending Central Middlesex Hospital in London were invited to complete a structured self-administered anonymous questionnaire. Eightysix young adults with HbSS, HbSC and HbSbthalassaemia disease (median age 30 years) participated in the study. Results showed that 31 (36%) had used cannabis in the previous 12 months to relieve symptoms associated with SCD. The main route in all but two patients was by smoking. The main reasons for use were to reduce pain in 52%, and to induce relaxation or relieve anxiety and depression in 39%. Symptoms related to sedation and mood effects were reported in 77% of patients. The majority of patients (58%) expressed their willingness to participate in studies of cannabis as a medicine. We conclude that research in the use of cannabinoids for pain relief in SCD would be both important and acceptable to adult patients.

Despite the major benefits of antiretroviral therapy on survival during HIV infection, there is an increasing need to manage symptoms and side effects during long-term drug therapy. Cannabis has been reported anecdotally as being beneficial for a number of common symptoms and complications in HIV infections, for example, poor appetite and neuropathy. This study aimed to investigate symptom management with cannabis. Following Ethics Committee approval, HIV-positive individuals attending a large clinic were recruited into an anonymous cross-sectional questionnaire study. Up to one-third (27%, 143/523) reported using cannabis for treating symptoms. Patients reported improved appetite (97%), muscle pain (94%), nausea (93%), anxiety (93%), nerve pain (90%), depression (86%), and paresthesia (85%). Many cannabis users (47%) reported associated memory deterioration. Symptom control using cannabis is widespread in HIV outpatients. A large number of patients reported that cannabis improved symptom control.

The National Obstetric Anaesthetic Database was established in 1998 to support collection of national data on obstetric analgesia and anaesthesia. The first year's project aimed to determine the incidence, characteristics, contributing factors and management of postpartum headaches with anaesthetic interventions. A total of 65348 women were reported to have had anaesthetic interventions. There were individual records of 404 women in whom postdural puncture headache (PDPH) was diagnosed (47 mild, 134 moderate, 202 severe and 21 unspecified) and 571 in whom headache was not related to dural puncture (315 mild, 176 moderate, 44 severe and 36 unspecified). Recognised dural puncture occurred in 165 women (41%), 130 (79%) during labour. Placement of spinal catheters on dural puncture in 51 women did not influence headache severity. Abdominal compression used to test the diagnosis of PDPH was only positive in 56/186 parturients (30%). Epidural blood patch was performed in 240 women with PDPH, of whom 101 women (42%) received their first blood patch within two days of delivery. The incidence of headache ranged from 1.1% to 1.9% between all anaesthetic techniques but increased to 11% for women receiving multiple regional anaesthetics. The predominant characteristics of PDPH were limitation of daily activity ( n =305, 75%), severity (moderate/severe) and a postural element ( n =325, 80%), all significantly different from headache from other causes ( P =0.001). Shoulder/neck stiffness ( n =172, 43%) was the commonest symptom associated with PDPH.

The management of pain differs if pain is self limiting or persistent; for example, if pain is prolonged then treatment will be managed by a multidisciplinary team in a pain clinic. Pain is not just from physical disorders but also from combinations of physiological, pathological, emotional, psychological, cognitive, environmental, and social factors (fig 1). The keys to successful pain control are the mechanisms that initiate and maintain pain. Major advances in neurobiology, from molecular studies to imaging the cortex of the brain, show the complex integration of nerve cell activity and have generated a fundamental change in attitude and expectation about the control of pain.1 Now, the public and health professionals expect to control pain by using preventive and active strategies, including drugs and physical and psychosocial interventions. Fig 1 Biopsychosocial factors that interact and modulate the experience of pain The topics we have chosen result from discussions with all grades of staff involved in the management of acute and chronic pain and range from new drug development based on scientific evidence that may impact on future pain management to a holistic approach to patient care. Our searches focused on the key words “pain,” “systematic review,” “management,” and “neuropathic.” We searched Medline, the Cochrane Library, and Health Technology Assessments, and we scrutinised the BMJ and the National Institutes of Health websites as well as professionally based websites for pain, such as that of the International Association for the Study of Pain and scientific websites such as that of the National Academy of Sciences. We identified systematic reviews from the past three years from these sources and leading scientific papers. #### Recent developments A major change in pain management is a move from empirical therapies to a mechanism based approach New drug developments are targeting specific receptor subtypes Pain assessment includes qualitative sensory affective and …

This study describes magnetic resonance imaging findings in women presenting with neurological complications associated with preeclampsia and eclampsia. One eclamptic and two preeclamptic women were studied after presenting with postpartum neurological events. In two women the brain increased in size on the initial follow-up images, following the same pattern seen in normal pregnancy. In the other woman, the brain was decreased in size at 13 days postpartum but increased in size at six weeks postpartum. This initial reduction in brain size may reflect the resolution of cerebral oedema resulting from underlying pathological processes.

The inspired partial pressure of an anaesthetic is often used as an index of arterial partial pressure in small animal experiments. We have investigated the influence of anaesthetic solubility on the ratio of arterial to inspired partial pressure in 24 rats, allocated randomly to receive halothane, isoflurane or desflurane at four different inspired concentrations. The arterial partial pressure of the volatile agent was measured by two-stage headspace analysis using a gas chromatograph calibrated with the same gas used to calibrate the Datex Capnomac that measured the inspired concentration. Mean values of arterial to inspired ratio at the lowest concentrations were 0.60 (95% confidence intervals 0.50, 0.71) for 0.8% halothane, 0.54 (0.38, 0.69) for 0.8% isoflurane, 0.72 (0.59, 0.86) for 1.5% sevoflurane and 0.71 (0.54, 0.87) for 4% desflurane. Analysis of variance showed a significant effect of anaesthetic agent (P = 0.008) on the arterial to inspired ratio. Thus volatile anaesthetic agents do not demonstrate a fixed arterial to inspired ratio in rats.

Pains after labor can be as severe as those experienced during labor, particularly the commonly occurring lower abdominal “after-pains” that are associated with prolonged uterine contractions during breast feeding. Other causes of lower abdominal pain may not be physiologically based but are either direct complications of parturition, such as genital infection, or fortuitous, such as appendicitis. Although the focus of pain control during pregnancy has been on labor and delivery, pain thresholds decrease postpartum. Maternity services have identified postpartum pain symptomatology to be a current health care issue. Anesthesiologists and physical health therapists must therefore develop an active role in this neglected area of women’s health.

Visceromotor and cardiovascular responses to colonic distension were measured in female rats, anesthetized with halothane in oxygen, in the proestrus, estrus, metestrus and diestrus phases of the estrous cycle. Ten rats were studied in each group and responses were measured at 5-min intervals for 60 min. A mixed model analysis of variance showed that there was no real change in either the visceral or cardiovascular response with time. There was a highly significant difference in visceromotor responses between the phases of the estrous cycle (P < 0.001). During the phase of proestrus the balloon pressure at which a response was triggered was much lower, with a mean value (95% confidence interval) of 18.7 (16.1, 21.8) mmHg, than the other phases with mean values (95% confidence interval) of 31.9 (27.4, 37.2) mmHg for estrus, 28.1 (24.2, 32.8) mmHg for metestrus, and 31.1 (26.7, 36.3) mmHg for diestrus. The mean arterial blood pressure increased in all groups (range 3.2, 5.4%) as a response to the stimulus, but there was no associated heart rate variability and no significant differences in cardiovascular changes between the groups (P = 0.6). The visceromotor responses measured during the phase of proestrus occurred at a significantly lower threshold than in the other phases of estrous.

Summary Thirty five women consented post partum to daily lumbar back pain assessments and magnetic resonance imaging (MRI) (0.15 Tesla) within 48 hours of delivery using a T 1 weighted spin echo and a fat suppression sequence (STIR) to identify tissue water. Nine women (26%) had lumbar disc abnormalities on MRI scan. Variable degrees of soft tissue changes in the lumbar region were observed using the STIR sequence in all patients after delivery. Eight women (23%) had mild, 15 (43%) moderate, and 12 (34%) severe changes with an average of 5 segments involved. These changes were reversible and related neither to the mode of delivery, nor to the trauma of epidural cannulation.

Changes in aortic blood flow were measured in rabbits with both normal and surfactant depleted lungs in order to elucidate the effect of different modes of ventilation on the circulation while optimizing arterial oxygenation (PaO2). Conventional mechanical ventilation (CMV), reversed inspiratory to expiratory ratio of CMV (IRV), high frequency positive pressure ventilation (HFV), and high frequency oscillation (HFO) were used. Normocapnia was maintained throughout during different modes of ventilation. In normal lungs the aortic blood flow during IRV was significantly lower with similar levels of PaCO2 compared with CMV, HFV, and HFO. In lavaged lungs, without positive end-expiratory pressure (PEEP), the aortic blood flow during CMV was significantly higher than with other modes of ventilation. When 10 cm H2O of PEEP was applied, the PaO2 increased maximally to normal values at all modes of ventilation, but the aortic blood flow was significantly reduced (P < 0.05) during CMV and IRV compared to HFV and HFO. The aortic blood flows at 5 cm H2O of PEEP were very similar during CMV, HFV, and HFO but significantly reduced during IRV. This study showed that at an optimal arterial oxygenation with higher PEEP levels, maintenance of aortic blood flow was maximal during HFV and HFO.

Forty obstetric patients were randomly allocated to receive either a midline or paramedian approach to the epidural space using loss of resistance to air. Tissue trauma was assessed by blinded observers, clinically by the presence of pain and radiologically using magnetic resonance imaging (MRI). Technical difficulties with imaging reduced those who were scanned to 10 in the paramedian group and 8 in the midline group. Lateralizing signs of tissue oedema were not related to the method of epidural cannulation. There was no significant difference in localized back pain between the two groups, and this was not related to MRI findings. Pain did not persist for more than 4 days.

This chapter provides a detailed overview of the worldwide pain management arena. A structured approach to the analgesic market has been to identify the frequency and type of pain, how it is managed (e.g., mechanism-based and evidence-based approaches), and what combinations of therapies are used, what the unfulfilled needs are for over-the-counter (OTC) and prescribers, and how to improve therapeutic strategies to achieve maximum benefit for patients. Keywords: pain management; analgesic market; over-the-counter drugs; step-up approach; step-down approach

We compared high frequency ventilation (HFV) to conventional mechanical ventilation (CMV) under normoxic and normocapnic condition in surfactant depleted rabbits with bilateral pneumothoraces. We hypothesized that lower airway pressures would be required with HFV under these conditions. We applied CMV and HFV in 8 anaesthetized rabbits with a prototype ventilator at frequencies of 30, 100,200, and 300 cycles/min. A positive end-expiratory pressure (PEEP) just below the pressure sufficient to open the air leak from the pneumothoraces was applied at all frequencies. Airway pressures, gas exchange, heart rate, and mean arterial pressure were recorded. Peak airway pressure decreased significantly from 2.50 to 2.10 kPa when the frequency of ventilation was increased from 30 to 300 cycleshnin. There were no significant changes in mean airway pressure, Pao2arterial pH, heart rate, and mean arterial pressure when HFV was compared to CMV. In conclusion, during HFV peak airway pressures measured at the mouth were decreased. Our ability to maintain adequate gas exchange in the face of ongoing pulmonary air leaks may reflect lower alveolar pressures. Pediatr Pulmonol. 1993; 16:354–357. © 1993 Wiley-Liss, Inc.

SUMMARY We have studied in anaesthetized dogs the effects of alfentanil, fentanyl, pethidine and lignocaine administered intrathecally on nociceptive responses evoked by low and high frequency supramaximal electrical stimulation of the tibial and radial nerves. Doses were selected to abolish both Aδ and C fibre somatosympathetic reflexes to single stimuli. Pethidine and lignocaine eliminated reflex pressor and heart rate responses to repeated single stimuli and almost completely abolished responses to train stimulation. The pressor response to single stimuli was abolished by fentanyl and reduced by alfentanil, but these drugs did not reduce significantly this response to train stimulation, suggesting a stimulation rate-dependent effect. Of the opioids, only pethidine had an effect comparable to that of lignocaine. The absence of sympathetic block and antagonism by naloxone imply a lack of significant local anaesthetic effect. We suggest that the greater analgesic efficacy of pethidine is a result of endogenous synergism between a minor local anaesthetic and a major opioid effect. (Br. J. Anaesth. 1993; 70 : 63–69)

The density of a drug in solution cannot be determined from a simple formula or from physico-chemical tables, because it depends on the physical state of that substance in solution. The densities of agents which have been reported to be administered by the intrathecal route were measured at room and body temperatures. The results were compared with the density of cerebrospinal fluid. At room temperature, most drugs were isobaric with respect to cerebrospinal fluid, but as drugs warmed to body temperature they became relatively hypobaric.

Understanding of the structure and function of the endocannabinoid system is rapidly evolving. Physiological and pharmacological manipulations based on cannabinoid receptors, ligands and endocannabinoids have explained some medicinal attributes of cannabinoids as used across the world for thousands of years. Plant-derived and synthetic cannabinoids are available for therapeutic use. Small clinical trials have demonstrated analgesic potential in acute and chronic pain. Regulatory and pharmacological limitations of these agents have hindered pain research in humans. Selective agonists, antagonists and metabolic targets to enhance endogenous cannabinoid activity are in development. Government reports in Europe and North America have encouraged research into the use of cannabinoids for pain relief and endorsed the clinical trials in acute and chronic pain. The results of large clinical trials into cannabinoid use for acute pain is expected to be the catalyst for wider studies and possible changes in legislation. Long-term effects of psychoactive cannabinoids require close monitoring and international cooperation to define their role, if any, in CNS disorders.

The issue of how sex and gender differences influence pain continues to be a focus of intense investigation at many levels of inquiry. Epidemiological studies consistently report a higher prevalence of chronic pain disorders in females in comparison to males. Indeed, very few persistent pain conditions show a higher male prevalence. Psychophysically, women will generally rate a stimulus as being noxious at a lower intensity level than males; however, there are many exceptions to this generalization, with individual and situational variations being greater than the sex differences. On the other hand, substantial sex and gender differences do appear to exist in the mechanisms by which pain is generated and relayed centrally. The many factors that underlie sex differences in pain mechanisms interact dynamically, and develop and change progressively throughout the life span of each individual. Sex differences in the actions of the gonadal steroids estradiol, progesterone, and testosterone have also been shown to contribute to these differences, affecting wide regions of the central and peripheral nervous system. However, despite their potency, gonadal steroids represent only one of many factors that influence the experience of pain. While these differences would appear to have potent clinical implications for the development of different strategies to diagnose and treat pain in women and men, it remains the case that such strategies are most effective when they are focused on the individual, with the sex of that individual being only one of many factors being considered.

Summary An automatically pressurised infusor system, the Alton Dean infusor, has been compared with two types (cloth and plastic) of commonly used pneumatically pressurised bags. All the infusors had reasonably accurate pressure gauges but pressure could only be consistently maintained with the cloth infusors or with the Alton Dean infusors when connected to a compressed air supply. Sequential fast infusions were possible with all infusors, but simultaneous infusions could be limited in number when the pressure infusor was connected directly to pipeline gas. One of the Alton Dean pressure infusors tested had a leak in the pressurisation system, and the pressure adjustment valves were difficult to manipulate. These may require modification.

A new, simple and inexpensive oscillatory ventilator is described in which a rotating jet mounted in the breathing duct generates cyclically positive and negative pressures in the airway with a sinusoidal flow waveform. Unlike conventional oscillatory ventilators it is free from restrictions to inspiratory or expiratory gas flows and open to atmosphere at all times, making it intrinsically a safe system for ventilation. A prototype rotating jet oscillatory ventilator designed for application in infants was evaluated in rabbits (mean weight 3.8 kg). The positive peak and mean airway pressures were significantly less during oscillatory ventilation at 300 and 420 b.p.m. compared with normal and high frequency positive pressure ventilation at 30 and 300 b.p.m., respectively, while maintaining blood-gas tensions within the normal range. An increase in the oscillatory frequency from 300 to 420 b.p.m. provided no further benefit in terms of airway pressure, tidal volume or blood-gas tensions.

OBJECTIVES This study aimed to compare data on the employment profiles (such as grade, place of work, etc.) of male and female clinical academics. METHODS We carried out a comparative review of workforce data within academic medicine for 2004 and 2005, pertaining to the workforce in all specialties in UK medical schools. RESULTS We identified 3255 and 3365 lecturers, senior lecturers, readers and professors in 2004 and 2005, respectively, of whom 21% were women. In 2004 and 2005, 12% and 11%, respectively, of 1157 and 1364 UK medical professors were women. The number of women filling such positions in individual schools ranged from 0% to 33% across schools. The total numbers of women post-holders and their full-time equivalents were similar, indicating that the majority of posts were full-time. CONCLUSIONS In England only 1 in 10 medical clinical professors are women. At the onset of the study period, 6 medical schools employed no female professors, with a consequent lack of female role models at these institutions. Large variations between schools suggest that some workforce practices may be detrimental to women's academic careers.

Background A variety of analgesics are used perioperatively and associated adverse drug reactions (ADRs) may complicate anaesthesia and recovery. Methods We aimed to measure the demographics of reported suspected ADRs to alfentanil, fentanyl, ketorolac, morphine, nalbuphine, papaveretum, pethidine and remifentanil. We report a retrospective analysis of Yellow Card reports of suspected ADRs from 1965–2004 as classified in the Adverse Drug Reaction On-line Tracking database (ADROIT) of the Medicines and Healthcare products Regulatory Agency (MHRA). Results In total, 1312 reactions were retrieved. A single drug was reported in 908, 39 were fatal and 219 categorised as ‘allergic’. Allergic phenomenon varied from 2/33 (6%) for remifentanil to 11/53 (21%) for alfentanil. ‘Cardiovascular’ reactions were reported frequently with remifentanil (18/33, 55%) and alfentanil (19/53, 36%) and these generated a signal for possible hazards from proportional reporting ratios (PRRs). The opioid fentanyl was associated with similar hazard signals for muscular and psychiatric ADRs. Conclusions Perioperative vigilance may reduce morbidity and mortality from preventable ADRs to analgesic drugs. Denominator and diagnostic data are essential for prospective studies. Copyright © 2007 John Wiley & Sons, Ltd.

En la decada pasada se ha acumulado cierta evidencia sobre las diferencias de sexo y genero en el dolor y en su alivio. Estimaciones de prevalencia de la enfermedad, estudios epidemiologicos y la investigacion psicofisica continuan mostrando que el problema del dolor es mayor, mas variado y mas variable en las mujeres que en los hombres, y que los hombres pueden infravalorar el dolor. Ademas, algunas enfermedades dolorosas se expresan de forma diferente entre hombres y mujeres, y ciertos tratamientos (farmacos, somaticos o situacionales) tienen una mayor eficacia en un sexo que en el otro. Esta cada vez mas claro que los factores interactivos geneticos, fisiologicos, anatomicos, neurales, hormonales, psicologicos, de estilo de vida y socioculturales contribuyen a estas diferencias a lo largo de la vida de cada individuo. Aunque los gobiernos y las agencias de investigacion cientifica se han percatado de la importancia de las diferencias de sexo y genero no solo para la salud sino tambien para la economia sanitaria, las diferencias todavia no estan totalmente reconocidas por los sistemas sanitarios en todos los paises. Sin embargo, esta situacion esta mejorando rapidamente, ya que la inclusion de los terminos sexo y genero aumenta no solo en el ambito de la investigacion basica y clinica sino tambien en las historias clinicas de dolor, el desarrollo de farmacos y los ensayos clinicos.

We determined the optimal inspired sevoflurane concentration for use during labour as 0.8% in our previous study. This study compared sevoflurane at a concentration of 0.8% and Entonox((R)) (nitrous oxide 50%: oxygen 50%) for analgesia during labour in 32 healthy parturients.Each mother underwent two open-label, three-part sequences in random order, Entonox-sevoflurane-Entonox or sevoflurane-Entonox-sevoflurane. In each part the agent was self-administered during 10 contractions. A 100 mm visual analogue scores for pain relief and sedation was completed immediately after each contraction.Two patients withdrew during administration of sevoflurane (because of its odour) and five during Entonox (requesting epidural analgesia). Of the remaining women, data were available for analysis from 29 participants: median (IQR [range]) pain relief scores were significantly higher for sevoflurane 67 (55-74 [33-100]) mm than for Entonox 51 (40-69.5 [13-100]) mm (P0.037). Nausea and vomiting were more common in the Entonox group [relative risk 2.7 (95% CI 1.3-5.7); P=0.004]. No other adverse effects were observed in the mothers or babies. There was significantly more sedation with sevoflurane than with Entonox {74 (66.5-81 [32.5-100]) and 51 (41-69.5 [13-100]) mm, respectively; P0.001}. Twenty-nine patients preferred sevoflurane to Entonox and found its sedative effects helpful.We conclude that self-administered sevoflurane at subanaesthetic concentration (0.8%) can provide useful pain relief during the first stage of labour, and to a greater extent than Entonox. Although greater sedative effects were experienced with sevoflurane, it was preferred to Entonox.

Anaesthetic drugs were selected from the Medicines and Healthcare products Regulatory Agency Drug Analysis Prints in order to determine the number and types of reported reactions and associated mortality.The chosen drug groups were the intravenous induction agents, the neuromuscular blocking drugs and neostigmine, the inhalational anaesthetic agents and nitrous oxide, local anaesthetic agents and a selection of analgesics agents, naloxone and midazolam and its antagonist flumazenil. From each drug file, the number and type of reactions were analysed. Mortality was calculated as a percentage of the number of deaths against patient reports.A total of 11,199 reactions were analysed from 6603 patients of whom 620 (9%) died. Few drug records reported reactions from multiple constituent formulations. The majority of reactions were not allergic. The highest mortality was in the inhalational anaesthetic group. Although the greatest number of fatal events was associated with halothane, this drug is no longer used. Nevertheless the percentage remains high because cardiovascular mortality is still being reported. Local anaesthetic use was associated with the smallest percentage mortality (3%). The highest reported number of reactions was associated with the intravenous induction agents and idiosyncratic neurological and peripheral vascular reactions were linked with the use of etomidate.The reporting of allergic reactions was low. The data demonstrate that induction of anaesthesia presents the highest risk of adverse drug reaction; there is also mortality from newer drugs for example, desflurane, remifentanil as well as from drugs for which there is no alternative, for example, suxamethonium.

Background Adverse drug reactions (ADRs) are known to occur during anaesthesia; in the U.K. such ADRs may be reported through the Yellow Card Scheme (YCS). Our aim was to determine the demographics of ADRs to neuromuscular blocking drugs without formal causality assessment. Methods A retrospective analysis of ADRs to seven neuromuscular blocking drugs reported via the YCS during a greater than 30-year period was performed. Sex and age were analysed in order to identify at risk groups. Results Of 998 reports, 969 included gender. Non-allergic suspected reactions occurred with almost the same frequency as those with an allergic component. The majority occurred in females 676 (70%), and significant sex differences were measured between drugs. Males were more likely to have suffered an ADR to atracurium (p = 0.01) whilst females experienced more ADRs to suxamethonium (p = 0.01). ADRs proved fatal in 81 (9%) of the 950 reports for single drugs. Mortality following suxamethonium was significantly higher in males at 22% compared with 9% females (p