Preliminary survey of the attitudes of Brazilian scientists towards pain management and assessment in animals used in science.

OBJECTIVE: To investigate the current scenario in Brazil regarding pain assessment and control in experimental animals. STUDY DESIGN: Prospective survey. METHODS: A confidential questionnaire was available online and sent by e-mail to Brazilian scientists working with animal experimentation in Brazil. Data collection was conducted from October 2016 to October 2017. The exclusion criteria included blank questionnaires or with <80% completed responses, researchers not performing experiments involving animals and foreign scientists. RESULTS: A total of 96 questionnaires from 104 respondents were analyzed. The Fisher's exact test showed a disparity between the proportions of scientists who recognized the importance of analgesia and their application of analgesic techniques in painful procedures (p < 0.0003), and also for the researchers who assumed that experiments inflicted pain and their classification of the degree of invasiveness (p < 0.0001), indicating their insufficient knowledge of these topics. Overall, 77% of institutions did not offer specific training to assess pain in experimental animals, and 24% of respondents had no training to work with animal experimentation. In total, 62% of the studies inflicted pain, 48% of respondents used pain scales, and the drugs administered most frequently for pain management were morphine (44%), meloxicam (43%) and tramadol (37%); 15% of respondents did not include analgesics even though their studies inflicted pain. Commonly used animals were rats (33%), mice (29%) and rabbits (8%). CONCLUSIONS AND CLINICAL RELEVANCE: The results of this preliminary survey indicated that in Brazil there is a gap in the knowledge and training on pain assessment and management of experimental animals. Therefore, there is a necessity for an educational program to prepare and train scientists to assess and manage pain in laboratory or experimental animals. Further studies using a psychometrically validated survey instrument are warranted.

Ethics of treating postoperative pain.

You received a call advising that Mr S. H. Irk was in the emergency room having considerable wound pain following an above-knee amputation you performed 6 months ago. You discharged him from your clinic 6 weeks postoperatively to his primary care physician, still complaining of more pain than usual. Your examination, clinical lab tests, and X-rays do not reveal any serious problems, but he is writhing in pain and begging for relief. Mr Irk has been to a number of different physicians in the interlude including a chiropractor, a pain specialist, several primary care physicians, and a psychiatrist without relief. He has braced up with increasing amounts of analgesics, the latest of which was oral Dilaudid. His last source of pain meds on the street has dried up. You admit him with orders for analgesics. What should your treatment plan be?

A physician-driven solution--the Association for Medical Ethics, the Physician Payment Sunshine Act, and ethical challenges in pain medicine.

The practice of contemporary pain medicine is laced with a number of significant ethical challenges. Considerable difficulties include the overutilization of interventional procedures, the application of under-evidenced treatment modalities, and potentially superfluous opioid prescribing. As with many other fields in medicine, including orthopedic surgery, relationships with industry are both common and pervasive, and influence our medical practice through education, publications, and research. This article highlights these ethical challenges and broaches several physician-driven solutions: The Association for Medical Ethics, the Physicians Payment Sunshine inspired by it, and other non-legislative reforms are discussed.

Four themes in recent Swedish bioethics debates.

A wide variety of bioethical themes have recently been debated and researched in Sweden, including genetic screening, HPV vaccination strategies, end-of-life care, injustices and priority setting in healthcare, dual-use research, and the never-ending story of scientific fraud. Also, there are some new events related to Swedish biobanking that might be of general interest. Here we will concentrate on four themes: end-of-life care, dual-use research, scientific fraud, and biobanking.

Why Would the Pope Have A Private Audience with Anesthesiologists? The Origin of the "Doctrine of Double Effect" and Its Application to Pain Control.

Sunday February 24, 1957 was a pivotal day in the history of anesthesiology and pain medicine. The leader of the Roman Catholic Church, Pope Pius XII met with anesthesiologists attending an international symposium sponsored by the Italian Society of Anesthesiologists entitled, "Anesthesia and the Human Personality". The purpose of this audience was to seek clarification about the use of opioids at the end of life to reduce suffering. Three questions had been formulated from the previous year's Italian Congress of Anesthesiologists and sent to the Holy See on this specific issue. The Pope responded during this audience remarking that there was no moral obligation to withhold pain medication that could elevate suffering. He further remarked that the suppression of consciousness that can occur with opioids was consistent with the spirit of the Christian gospels. Finally, he also stated that it was not morally objectionable to administer opioids even if it might shorten life. The moral philosophy behind these answers is the doctrine of double effect. In essence, administering medications to relieve pain, the primary effect, may also hasten death, the unintended secondary effect. In seeking answers to these questions, the Italian anesthesiologists were at the forefront of a larger and ongoing debate. As new therapies are developed that may have unintended consequences, when it is morally permissible to use them?

Undertreating pain violates ethical principles.

Disabling pain or symptoms can occur at any age from many different causes. Pain and palliative specialists are able to relieve most pain and symptoms, although repeated adjustments to modalities, medications and doses may be needed. Because pain and palliative specialists comprise only a small percentage of physicians, many patients find it difficult to access them or obtain pain relief. Globally, there are too few such specialists to meet existing needs. Most are affiliated with hospice and palliative units, so their accessibility to patients without terminal conditions is negligible. Doctors outside pain and palliative specialties are often unfamiliar with pain guidelines and sceptical about patient reports of unrelieved pain. They are therefore likely to undertreat it. Undertreating pain, however, violates respect for persons and beneficence. This paper reviews literature supporting these claims and offers a narrative description of the author's attempts to find relief from shingles and postherpetic neuralgia. It argues that physicians in most specialties are not, but should be, familiar with palliative evidence and guidelines so that they are equipped to relieve pain and symptoms quickly and effectively. Such information should be routinely introduced in medical curricula to encourage the mastery of knowledge, attitudes and skills necessary to upholding ethical principles and to ensure that more doctors in any discipline are willing to believe and be compassionate to patients whose pain is unresponsive to initial treatments. Routinely exposing students to such information would better prepare them to fulfil their professional duties to patients and society.

Ethical and IACUC Considerations Regarding Analgesia and Pain Management in Laboratory Rodents.

Scientists have ethical and regulatory commitments to minimize pain and distress during their use of sentient laboratory animals. Here I discuss pain as a special form of distress and the long history of ethical and regulatory standards calling on scientists to prevent, minimize, treat or terminate animal pain. Scientists, veterinarians, and IACUC face 2 challenges: knowledge of effective analgesic doses and regimens for all sexes, ages and genotypes of rodent is incomplete, and concerns regarding the effects of analgesic drugs on research outcomes push scientists to request approval to withhold analgesics and leave animal pain unalleviated. IACUC thus conduct what I call an 'ethics of uncertainty,' in which they factor in the limits of available ethically relevant information on the amount of expected animal suffering, the usefulness of analgesics to mitigate this suffering, and the eventual benefits that come from the research. IACUC must factor in current limitations in severity assessments of various experimental manipulations in various strains, inaccurate pain diagnosis, in known effective analgesic and other refinements, and on effects of pain medications and untreated pain on data outcomes, when deciding to allow potentially painful experiments and animal care practices. This article focuses on 3 areas of concern: the limits of veterinary "professional judgment" when the animal model's degree of pain and the efficacy of pain medications are not yet known; the review of proposals with known, unalleviated significant pain and distress (that is, Category E experiments); and the attempt to review the balance between animal welfare harms and scientific objectives. I propose no new regulations, standards, or ethical norms herein but rather explore some of the implications when existing ethical principles are applied to evolving scientific knowledge (and vice versa). I conclude that applying current animal pain management knowledge to prevailing ethical principles will shift IACUC toward greater caution in allowing potentially painful animal experiments, with heightened caution regarding the ability of analgesics to mitigate the animals' pain.

On the nature, assessment, and treatment of fetal pain: neurobiological bases, pragmatic issues, and ethical concerns.

Over the past 2 decades, the issue of fetal pain and stress has attracted considerable attention and has become the focus of ongoing debate in light of advances in medical diagnostics and technology that allow invasive prenatal medical intervention(s), and an enhanced understanding of fetal neurophysiology, together with a broadened appreciation for the relationship of brain and consciousness. In this essay, we explore the issue of fetal pain based upon knowledge of both the ontogeny and function of the nervous system and the interaction of brain, mind, and pain. We posit that contemporary understanding of neurological development fortifies appreciation that pain sensation and perception occurs during (later) fetal life and that this pain warrants clinical consideration during the conduct of invasive prenatal procedures. We present differing perspectives on this issue, discuss the relative merits and difficulties of these positions, and ultimately describe the fundamental basis for a consideration of fetal pain and address this consideration with regard to pragmatic and ethical benefits, burdens, and risks. We adopt a neurocentric, yet consilient approach that entails both scientific and philosophical orientations. By attempting to reveal inherent limitations in our contemporary appreciation and approach(es) to fetal pain, we hope to illustrate the need for and posit potential venues toward resolving these limitations and dilemmas.

Opioid analgesia: perspectives on right use and utility.

The ability of opioids to effectively and safely control acute and cancer pain has been one of several arguments used to support extending opioid treatment to patients with chronic pain, against a backdrop of considerable caution that has been based upon fears of addiction. Of course, opioids may cause addiction, but the "principle of balance" may justify that "...efforts to address abuse should not interfere with legitimate medical practice and patient care." Yet, situations are increasingly encountered in which opioid-maintained patients are refractory to analgesia during periods of pain, or even during the course of chronic treatment. The real question is whether analgesic efficacy of opioids can be maintained over time. Overall, the evidence supporting long-term analgesic efficacy is weak. The putative mechanisms for failed opioid analgesia may be related to tolerance or opioid-induced hyperalgesia. Advances in basic sciences may help in understanding these phenomena, but the question of whether long-term opioid treatment can improve patients' function or quality of life remains a broader issue. Opioid side effects are well known, but with chronic use, most (except constipation) subside. Still, side effects can negatively affect the outcomes and continuity of therapy. This paper addresses 1) what evidence supports the long-term utility of opioids for chronic pain; 2) how side effects may alter quality of life; 3) the nature of addiction and why it is different in pain patients, and 4) on what grounds could pain medication be denied? These questions are discussed in light of patients' rights, and warrant balancing particular responsibilities with risks. These are framed within the Hippocratic tradition of "producing good for the patient and protecting from harm," so as to enable 1) more informed clinical decision making, and 2) progress towards right use and utility of opioid treatment for chronic pain.

Analgesia and anesthesia for neonates: study design and ethical issues.

OBJECTIVE: The purpose of this article is to summarize the clinical, methodologic, and ethical considerations for researchers interested in designing future trials in neonatal analgesia and anesthesia, hopefully stimulating additional research in this field. METHODS: The MEDLINE, PubMed, EMBASE, and Cochrane register databases were searched using subject headings related to infant, newborn, neonate, analgesia, anesthesia, ethics, and study design. Cross-references and personal files were searched manually. Studies reporting original data or review articles related to these topics were assessed and critically evaluated by experts for each topical area. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were abstracted and synthesized in a systematic manner and refined by group members. Data synthesis and results were reviewed by a panel of independent experts and presented to a wider audience including clinicians, scientists, regulatory personnel, and industry representatives at the Newborn Drug Development Initiative workshop. Recommendations were revised after extensive discussions at the workshop and between committee members. RESULTS: Designing clinical trials to investigate novel or currently available approaches for analgesia and anesthesia in neonates requires consideration of salient study designs and ethical issues. Conditions requiring treatment include pain/stress resulting from invasive procedures, surgical operations, inflammatory conditions, and routine neonatal intensive care. Study design considerations must define the inclusion and exclusion criteria, a rationale for stratification, the confounding effects of comorbid conditions, and other clinical factors. Significant ethical issues include the constraints of studying neonates, obtaining informed consent, making risk-benefit assessments, defining compensation or rewards for participation, safety considerations, the use of placebo controls, and the variability among institutional review boards in interpreting federal guidelines on human research. For optimal study design, investigators must formulate well-defined study questions, choose appropriate trial designs, estimate drug efficacy, calculate sample size, determine the duration of the studies, identify pharmacokinetic and pharmacodynamic parameters, and avoid drug-drug interactions. Specific outcome measures may include scoring on pain assessment scales, various biomarkers and their patterns of response, process outcomes (eg, length of stay, time to extubation), intermediate or long-term outcomes, and safety parameters. CONCLUSIONS: Much more research is needed in this field to formulate a scientifically sound, evidence-based, and clinically useful framework for management of anesthesia and analgesia in neonates. Newer study designs and additional ethical dilemmas may be defined with accumulating data in this field.

APS position statement on the use of placebos in pain management.

In the spring of 2003, the board of directors of the American Pain Society asked the APS Ethics Committee to formulate a position statement for the Society concerning the use of placebos in clinical practice (cf, reference ). A subset of the Ethics Committee under my direction composed such a statement based on the available scientific and ethical literature. We then sought feedback from the entire ethics committee as well as numerous prominent voices in the literature and presented the statement to the membership for discussion at the 2004 annual APS meeting in Vancouver, British Columbia, at both a symposium and an ethics special interest group meeting. The resultant document was approved by the APS Board and is published here for widespread distribution to the membership.

Terminal dyspnea and respiratory distress.

Dyspnea is a subjective experience that can be reported by the patient. Respiratory distress is an observable corollary, and represents the physical or emotional suffering that results from the experience of dyspnea. Recognizing and understanding this subjective phenomenon poses a challenge to intensive care unit (ICU) clinicians when caring for the patient who is dying in the ICU. Dyspnea and cognitive impairment are highly prevalent in the terminally ill ICU patient. A Respiratory Distress Observation Model may provide a theoretical foundation for the assessment of this phenomenon that is grounded in emotional and autonomic domains of neurologic function. Treatment of dyspnea and respiratory distress relies on nonpharmacologic interventions and opioids and sedatives. As with pain, the treatment of dyspnea and respiratory distress relies on close evaluation of the patient and treatment to satisfactory effect. Empirical evidence suggests that quality care with control of distressing symptoms does not hasten death. Withholding opioids or sedatives in the face of unrelieved dyspnea or respiratory distress has no moral foundation.

End-of-life care in the pediatric intensive care unit: research review and recommendations.

Improving the quality of end-of-life care has become a national health care priority. A necessary step in this process in the pediatric intensive care unit (ICU) is examining the knowledge, attitudes,and behaviors of pediatric critical care practitioners in this area. In addition, the perspectives of bereaved parents must be uncovered as well. In this article, the empirical data in the literature on end-of-life care in the pediatric ICU are reviewed, common ethical controversies in this environment are discussed, and promising interventions for the future are presented.

Postoperative analgesics in South African Clawed frogs (Xenopus laevis) after surgical harvest of oocytes.

Heightened awareness for the welfare of earlier-evolved laboratory species has prompted increasing inquiries by institutional animal care committees, investigators, and laboratory animal veterinarians regarding the need for post-surgical analgesics in laboratory Xenopus. Basic research into the mechanisms and regulation of pain in Rana pipiens has demonstrated the clinical potential of opioid, alpha2-adrenergic, and non-opioid analgesic agents in amphibians. However, clinical studies using objectively established indices of amphibian pain, or pharmacological studies in either Rana pipiens or laboratory Xenopus have not been conducted. As discussed above, comparison of limited lethality data suggests that the safety index for these agents is quite narrow in Rana pipiens. Analgesic use in laboratory Xenopus has the added risk of drowning due to over sedation. Drug doses extrapolated from such studies and intended to provide pain relief in Xenopus should therefore be considered very carefully. An additional concern for laboratory Xenopus is that the effects of these agents on amphibian oogenesis, oocyte quality, and embryogenesis are unknown. As the numbers of laboratory Xenopus used in basic and biomedical research continues to increase, clinical studies that address all of these issues cannot come too soon.