Administration Of Opioid Analgesics Research Articles

FDA Approves Powerful Opioid Amid Controversy Over Risks

FDA Approves Powerful Opioid Amid Controversy Over Risks

Pre-emptive and preventive opioids for postoperative pain in adults undergoing all types of surgery.

Postoperative pain is a common consequence of surgery and can have deleterious effects. It has been suggested that the administration of opioid analgesia before a painful stimulus may improve pain control. This can be done in two ways. We defined 'preventive opioids' as opioids administered before incision and continued postoperatively, and 'pre-emptive opioids' as opioids given before incision but not continued postoperatively. Both pre-emptive and preventive analgesia involve the initiation of an analgesic agent prior to surgical incision with the aim of reducing intraoperative nociception and therefore postoperative pain. To assess the efficacy of preventive and pre-emptive opioids for reducing postoperative pain in adults undergoing all types of surgery. We searched the following electronic databases: CENTRAL, MEDLINE, Embase, AMED, and CINAHL (up to 18 March 2018). In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles. We did not apply any restrictions on language or date of publication. We included parallel-group randomized controlled trials (RCTs) only. We included participants aged over 15 years old undergoing any type of surgery. We defined postincision opioids as the same intervention administered after incision whether single dose (as comparator with pre-emptive analgesia) or continued postoperatively (as comparator with preventive analgesia) (control group). We considered studies that did and did not use a double-dummy placebo (e.g. intervention group received active drug before incision and placebo after incision; control group received placebo before incision and active drug after incision). We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: early acute postoperative pain (measured within six hours and reported on a 0-to-10 scale) and respiratory depression. Our secondary outcomes included: late acute postoperative pain (24 to 48 hours and reported on a 0-to-10 scale), 24-hour morphine consumption, and adverse events (intraoperative bradycardia and hypotension). We used GRADE to assess the quality of the evidence for each outcome. We included 20 RCTs, including one unpublished study with 1343 participants. Two studies were awaiting classification as the full text for these studies was not available. One study evaluated pre-emptive opioids, and 19 studies evaluated preventive opioids. We considered only one study to be at low risk of bias for most domains. The surgeries and opioids used varied, although roughly half of the included studies were conducted in abdominal hysterectomy, and around a quarter used morphine as the intervention. All studies were conducted in secondary care.Pre-emptive opioids compared to postincision opioidsFor pre-emptive opioids in dental surgery, there may be a reduction in early acute postoperative pain (mean difference (MD) -1.20, 95% confidence interval (CI) -1.75 to -0.65; 40 participants; 1 study; low-quality evidence). This study did not report on adverse events (respiratory depression, bradycardia, or hypotension). There may be a reduction in late acute postoperative pain (MD -2.10, 95% CI -2.57 to -1.63; 40 participants; 1 study; low-quality evidence). This study did not report 24-hour morphine consumption.Preventive opioids compared to postincision opioidsFor preventive opioids, there was probably no reduction in early acute postoperative pain (MD 0.11, 95% CI -0.32 to 0.53; 706 participants; 10 studies; I2 = 61%; moderate-quality evidence). There were no events of respiratory depression in four studies (433 participants). There was no important reduction in late acute postoperative pain (MD -0.06, 95% CI -0.13 to 0.01; 668 participants; 9 studies; I2 = 0%; moderate-quality evidence). There may be a small reduction in 24-hour morphine consumption (MD -4.91 mg, 95% CI -9.39 mg to -0.44 mg; 526 participants; 11 studies; I2 = 82%; very low-quality evidence). There may be similar rates of bradycardia (risk ratio (RR) 0.33, 95% CI 0.01 to 7.88; 112 participants; 2 studies; I2 = 0%; low-quality evidence) and hypotension (RR 1.08, 95% CI 0.25 to 4.73; 88 participants; 2 studies; I2 = 0%; low-quality evidence). Due to the low quality of the evidence, we are uncertain whether pre-emptive opioids reduce postoperative pain. Based on the trials conducted thus far, there was no clear evidence that preventive opioids result in reductions in pain scores. It was unclear if there was a reduction in morphine consumption due to very low-quality of evidence. Too few studies reported adverse events to be able to draw any definitive conclusions. Once assessed, the two studies awaiting classification may alter the conclusions of the review.

A Novel Approach to Safer Analgesics: Mu Opioid Receptor Agonist & Delta Opioid Receptor Antagonist Peptidomimetics

Opioid analgesics exert their therapeutic and unwanted effects by activation of the mu‐opioid receptor (MOR). Repeated administration of opioid analgesics and subsequent chronic MOR activation promotes opioid tolerance and physical dependence. It has been proposed that activation of MOR with concurrent antagonism of the delta‐opioid receptor (DOR) can attenuate the development of opioid tolerance and dependence. To further investigate the utilization of concurrent MOR agonism and DOR antagonism we designed, synthesized, and characterized a library of “peptidomimetics” that have elements of opioid peptides vital for activity but retain small molecule‐like features necessary for blood‐brain‐barrier penetration. Compounds were evaluated in membrane preparations of cloned cell lines expressing either MOR, DOR, or kappa‐opioid receptors (KOR). [35S]‐GTPγS binding to measure G protein‐coupled activation was used. Full agonists at each opioid receptor (DAMGO, DPDPE, and U69,593, respectively) were employed as standards. Maximum binding and potency (EC50) values were determined from concentration‐effect curves. To measure affinity (Ki) values, competition binding using [3H]‐diprenorphine was performed. Peptidomimetics that demonstrated promising bi‐functional activity were tested for antinociceptive activity in vivo. Compared to repeated morphine‐treated mice, repeated peptidomimetic treated mice developed less analgesic tolerance or physical dependence. Analysis of in vitro and in vivo data has permitted structure‐activity relationships to guide further chemical synthesis and the discovery of opioid analgesics that may have improved clinical utility.Support or Funding InformationSupported by DA‐03910This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hydromorphone use for acute pain: Misconceptions, controversies, and risks.

Hydromorphone (HM) is a potent opioid analgesic that is commonly administered in the emergency department (ED) and other acute care settings, such as medical surgical wards. In recent years, there has been a significant increase in the ED administration of HM relative to other opioids. Although HM is an effective analgesic, its use has been commonly implicated in adverse drug events and medication errors. In addition, intravenous HM has potent euphoric effects that may contribute to its abuse liability. There are limited data regarding how acute parenteral administration of opioid analgesics in the setting of high rates of preexisting chronic opioid use (medical or nonmedical) may contribute to or reinforce addictive behavior, making the potential contribution of rising HM administration to subsequent prescription opioid abuse and overdose uncertain. This review addresses the pharmacology of HM, recommended dosing, its efficacy for acute pain, as well as its tolerability, safety, and abuse profiles. Controversies and strategies for appropriate use of this medication are also described.

Perception and Practice Among Emergency Medicine Health Care Providers Regarding Discharging Patients After Opioid Administration

PurposeThis study aimed to determine the current attitudes, perceptions, and practices of emergency medicine providers and nurses (RNs) regarding the discharge of adult patients from the emergency department (ED) after administration of opioid analgesics. MethodsA cross-sectional survey was administered at 3 hospital sites with a combined annual ED census of >180,000 visits per year. All 59 attending emergency physicians (EPs), 233 RNs, and 23 advanced practice clinicians (APCs) who worked at these sites were eligible to participate. FindingsThirty-five EPs (59.3%), 88 RNs (37.8%), and 14 APCs (60.9%) completed the survey for an overall response rate of 51.75%. Most respondents were female (95 [69.9%]). The factor ranked most important to consider when discharging a patient from the ED after administration of opioids was the patient’s functional status and vital signs (median, 2.00; interquartile range, 2.00–3.50). More RNs (84 [96.6%]) than EPs (29 [82.9%]) reported that developing an ED policy or guideline for safe discharge after administration of opioids is important to clinical practice (P = 0.02). Only 8 physicians (23.5%) reported that they did not prescribe intramuscular morphine, and 15 (42.9%) reported that they did not prescribe intramuscular hydromorphone. EPs (7 [20.0%]) and RNs (3 [3.4%]) differed in regard to whether they were aware if any patients to whom they administered an opioid had experienced an adverse drug-related event (P = 0.01). Most EPs (24 [68.6%]) and RNs (54 [61.4%]) believed that the decision for patient discharge should be left to both the emergency medicine provider and the RN. ImplicationsMost study participants believed that developing a policy or guideline for safe discharge after administration opioids in the ED is important to clinical practice. Only a few physicians reported that they did not prescribe intramuscular hydromorphone or morphine. Most participants believed the discharge decision after administration of opioids in the ED should be primarily determined by both the emergency medicine provider and the RN.

Are We Adequately Treating Pain in Children Who Present to US Emergency Departments?: Factors That Contribute to Pain Treatment in Pediatric Patients.

There are no recent national data on analgesic use for pain treatment in children. Our objective was to determine if there is adequate pain treatment for children in US emergency departments (EDs) and determine predictors of nonopioid and opioid analgesic administration. Children younger than 18 years with the diagnosis of extremity fracture, appendicitis, or urinary tract stones were obtained from the National Health Ambulatory Medical Care Survey (NHAMCS) (2006-2010) and analyzed using logistic regression for complex samples. There were 2 analyses: (1) those who received analgesics versus those who did not; and (2) of those who received analgesics, opioid versus nonopioid analgesic use. There were 1341 records analyzed representing 4.5 million ED visits. Those who received analgesics were more likely to be older than age of 3 years (P = 0.05), be discharged from the hospital (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.04-2.94), arrive between noon and midnight (OR, 0.1.85; CI, 1.12-3.03), and have a higher pain rating (P < 0.01). Children who received opioid analgesics were more likely to live outside the Northeast (P = 0.04), require admission (OR, 2.95; CI, 1.09-7.98), have a higher acuity triage level (OR, 1.79; CI, 1.04-3.06), have higher pain scores (P < 0.01), and have private insurance (OR, 1.75; CI, 1.06-2.94). There is still a lot of room for improvement of pediatric pain control in US EDs. We aim to apply this information toward direct physician and nursing education interventions, including the recognition of age appropriate pain cues, and parental information and guidance to improve pediatric pain treatment in US EDs.

Project for the introduction of prehospital analgesia with fentanyl and morphine administered by specially trained paramedics in a rural service area in Germany.

BackgroundIn patients with serious illness or trauma, reduction of severe pain is a key therapeutic goal of emergency medical service (EMS) teams. In Germany, only physicians are allowed to use opioid analgesics. In the rural EMS area studied, the mean arrival time for paramedics is 8 minutes, 23 seconds, and for the rescue physician between 10 minutes, 30 seconds and 16 minutes, 59 seconds, depending on EMS site. In cases of parallel callouts, rescue-physician arrival times may be considerably longer.ObjectiveDuring this project, we assessed the administration of the opioid analgesics morphine and fentanyl by specially trained paramedics with regard to analgesia quality and patient safety.Materials and methodsDuring the 18-month study period, specially trained paramedics administered morphine or fentanyl to patients with severe pain if indicated and if a rescue physician was not available in time. Besides basic documentation, pain intensity (using a numeric rating scale) and oxygen saturation were measured initially and at hospital handover.ResultsDuring the 18 months, 4,285 emergency callouts were attended to by the 13 specially trained paramedics of the district (total callouts during this period 21,423). In 77 patients (1.8%), fentanyl (n=53/68.8%) or morphine (n=24/31.2%) was administered. Based on the measurements obtained with the numeric rating scale at the start of treatment (7.9) and upon hospital handover (3.3), pain reduction was 4.52 overall (41.5%, P<0.001): 4.64 with fentanyl (42.9%, P<0.001) and 4.25 with morphine (43.2%, P<0.001). None of the patients had an oxygen saturation <95% at the time of handover, and no patient developed opioid-induced respiratory depression requiring treatment.ConclusionThe results of this study indicate that the administration of opioid analgesics by specially trained and qualified paramedics is safe and effective.

Opioid analgesic administration in patients with suspected drug use.

To identify the prevalence of patients suspected of drug use according to the nursing professionals' judgement, and compare the behavior of these professionals in opioid administration when there is or there is no suspicion that patient is a drug user. A cross-sectional study with 507 patients and 199 nursing professionals responsible for administering drugs to these patients. The Chi-Square test, Fisher's Exact and a significance level of 5% were used for the analyzes. The prevalence of suspected patients was 6.7%. The prevalence ratio of administration of opioid analgesics 'if necessary' is twice higher among patients suspected of drug use compared to patients not suspected of drug use (p = 0.037). The prevalence of patients suspected of drug use was similar to that of studies performed in emergency departments. Patients suspected of drug use receive more opioids than patients not suspected of drug use. Identificar a prevalência de pacientes com suspeita de uso de drogas conforme opinião de profissionais de enfermagem e comparar a conduta desses profissionais na administração de opioides quando há ou não suspeita de que o paciente seja usuário de drogas. Estudo transversal com 507 pacientes e 199 profissionais de enfermagem responsáveis pela administração de medicamentos a esses pacientes. Para as análises foram utilizados os testes de Qui-Quadrado, Exato de Fisher e um nível de significância de 5%. A prevalência de pacientes suspeitos foi 6,7%. A razão de prevalência de administração de analgésicos opioides "se necessário" é duas vezes maior entre os pacientes suspeitos em relação aos não suspeitos (p=0,037). A prevalência de suspeitos foi semelhante à de estudos realizados em departamentos de emergência. Os suspeitos de serem usuários de drogas recebem mais opioides do que os não suspeitos.

Do we feel pain during anesthesia? A critical review on surgery-evoked circulatory changes and pain perception.

The difficulty of defining the three so-called components of « an-esthesia » is emphasized: hypnosis, absence of movement, and adequacy of anti-nociception (intraoperative«analgesia »). Data obtained from anesthetized animals or humans delineate the activation of cardiac and vasomotor sympathetic reflex (somato-sympathetic reflex) and the cardiac parasympathetic deactivation observed following somatic stimuli. Sympathetic activation and parasympathetic deactivation are used as monitors to address the adequacy of intraoperative anti-nociception. Finally, intraoperative nociception through the administration of nonopioid analgesics vs. opioid analgesics is considered to achieve minimal postoperative side effects.

Theory of Planned Behavior Constructs Associated with Nurses’ Pain Assessment and Pro Re Nata (PRN) Opioid Analgesic Administration: A Cross-sectional Study

Little theory-based research has been performed to better understand nurses' perceptions of pain management. Framed by the theory of planned behavior, the aims of the study were to describe nurses' beliefs (behavioral, normative, and control) about pain management for hospitalized elderly patients with postoperative pain; to present an item analysis for beliefs, attitudes, perceived norms, perceived behavioral control, intentions, and behaviors (measured in case study vignettes) for nurses (a) with different durations of nursing experience, (b) working in university, public health, and military hospitals, and (c) who either had or had not received pain management training in the past six months; and to compare differences in the constructs across these three groups. A comparative descriptive cross-sectional design was used with a convenience sample of 140 Thai nurses working in three Bangkok hospitals. Participants responded to pain assessment and management questionnaires. Most nurses expressed fairly strong beliefs about pain assessment and pro re nata (PRN) opioid analgesic administration. Nurses with more than 10 years of experience had the highest scores for attitudes toward pain assessment and perceptions of others’ expectations about PRN opioid analgesic administration. Responses of nurses working in different types of hospitals indicated significantly different pain assessment and PRN opioid analgesic administration behaviors. No significant differences were found for nurses who did and did not receive pain management training. The study highlighted the need for improved pain management education for nurses to enhance the quality of patient care.

Timing of postoperative respiratory emergencies: when do they really occur?

Opioid-induced postoperative respiratory depression has garnered attention and calls for vigilance. However, a higher level of monitoring equates to increased use of hospital resources and is impractical to apply for all postoperative patients. Understanding the temporal pattern of postoperative respiratory emergency occurrences would allow for improved triage of monitoring resources for high-risk patients. Our objective is to describe the temporal pattern of risk of postoperative opioid-induced respiratory failure. The literature suggests that postoperative opioid-induced respiratory depression is more frequent and severe than previously believed. In response, national patient advocacy groups have proposed improved postoperative monitoring of high-risk patients, especially those with sleep-disordered breathing. Published series of patients who have had adverse respiratory events suggest that the first 24 postsurgical hours comprise the period of highest risk, with most events occurring within the first 12 h. Further, study findings have suggested that adverse respiratory events often occur shortly after administration of opioid analgesics. Emerging evidence indicates that the first postsurgical day carries the highest risk of adverse respiratory events, and this risk is often associated with opioid administration. Resources for increased monitoring should be directed to these high-risk times.

Psychosocial factors predict opioid analgesia through endogenous opioid function.

Use of opioid analgesics for management of chronic nonmalignant pain has become common, yet there are presently no well-validated predictors of optimal opioid analgesic efficacy. We examined whether psychosocial factors (eg, depressive symptoms) predicted changes in spontaneous low back pain after administration of opioid analgesics, and whether endogenous opioid (EO) function mediated these relationships. Participants with chronic low back pain but who were not chronic opioid users (N = 89) underwent assessment of low back pain intensity pre- and post-drug in 3 (counterbalanced) conditions: (1) placebo, (2) intravenous naloxone, and (3) intravenous morphine. Comparison of placebo condition changes in back pain intensity to those under naloxone and morphine provided indexes of EO function and opioid analgesic responses, respectively. Results showed that (1) most psychosocial variables were related significantly and positively to morphine analgesic responses for low back pain, (2) depressive symptoms, trait anxiety, pain catastrophizing, and pain disability were related negatively to EO function, and (3) EO function was related negatively to morphine analgesic responses for low back pain. Bootstrapped mediation analyses showed that links between morphine analgesic responses and depressive symptoms, trait anxiety, pain catastrophizing, and perceived disability were partially mediated by EO function. Results suggest that psychosocial factors predict elevated analgesic responses to opioid-based medications, and may serve as markers to identify individuals who benefit most from opioid therapy. Results also suggest that people with greater depressive symptoms, trait anxiety, pain catastrophizing, and perceived disability may have deficits in EO function, which may predict enhanced response to opioid analgesics.

206 Predictors of Hydromorphone Administration in US Emergency Departments, 2007-2011

The past two decades have seen dramatic increases in the administration of opioid analgesics in U.S. EDs, particularly hydromorphone. Hydromorphone is a high-potency semi-synthetic opioid with significant abuse potential. The potential contribution of rising ED hydromorphone administration to prescription opioid abuse and overdose nationally is uncertain but concerning. This study examines recent trends and in and predictors of hydromorphone administration in U.S. EDs. A retrospective review of data from the National Hospital Ambulatory Medical Care Survey (NHAMCS), from 2007-2011 was performed. All adult encounters during which an opioid analgesic was administered in the ED were included. Discharge prescriptions were not included. Trends in overall hydromorphone administration and predictors of visits where hydromorphone was administered as compared to visits where other opioids (ie, morphine, oxycodone, etc.) were administered were assessed using logistic regression analysis. An estimated 245.6 million visits were included. Hydromorphone administration increased 24.4%, from 8.2% of visits in 2007 to 10.2% in 2011, p=0.007. Patient characteristics associated with hydromorphone administration compared to other opioids included age <65 years, white race, having private insurance or Medicare, having more than 2 visits in the past year, and a report of severe pain (pain score ≥ 8). Visit characteristics associated with an increased likelihood of hydromorphone administration included ordering of bloodwork, having a procedure performed, and admission to a general medical/surgical unit. Several conditions were associated with higher rates of hydromorphone administration, particularly back pain. Hydromorphone was more likely to be administered in hospitals in the Midwest, west, and south, those in urban areas, and non-teaching hospitals (Table). There was a significant increase in hydromorphone administration in U.S. EDs from 2007-11, with severity of reported pain being the strongest predictor for hydromorphone use. Hydromorphone administration was associated with conditions for which opioid use is controversial, such as back pain and headache as well as for patients with multiple ED visits.

250 Predictors of Opioid Analgesic Administration for Abdominal Pain in the Emergency Department

250 Predictors of Opioid Analgesic Administration for Abdominal Pain in the Emergency Department

Multicenter Evaluation of Prehospital Opioid Pain Management in Injured Children

Background: The National Association of Emergency Medical Services Physicians’ (NAEMSP) Position Statement on Prehospital Pain Management and the joint National Highway Traffic Safety Administration (NHTSA) and Emergency Medical Services for Children (EMSC) Evidence-based Guideline for Prehospital Analgesia in Trauma aim to improve the recognition, assessment, and treatment of prehospital pain. The impact of implementation of these guidelines on pain management in children by emergency medical services (EMS) agencies has not been assessed. Objective: Determine the change in frequency of documented pain severity assessment and opiate administration among injured pediatric patients in three EMS agencies after adoption of best practice recommendations. Methods: This is a retrospective study of children <18 years of age with a prehospital injury-related primary impression from three EMS agencies. Each agency independently implemented pain protocol changes which included adding the use of age-appropriate pain scales, decreasing the minimum age for opiate administration, and updating fentanyl dosing. We abstracted data from prehospital electronic patient records before and after changes to the pain management protocols. The primary outcomes were the frequency of administration of opioid analgesia and documentation of pain severity assessment as recorded in the prehospital patient care record. Results: A total of 3,597 injured children were transported prior to pain protocol changes and 3,743 children after changes. Opiate administration to eligible patients across study sites regardless of documentation of pain severity was 156/3,089 (5%) before protocol changes and 175/3,509 (5%) after (p = 0.97). Prior to protocol changes, 580 (18%) children had documented pain assessments and 430 (74%) had moderate-to-severe pain. After protocol changes, 644 (18%) patients had pain severity documented with 464 (72%) in moderate-to-severe pain. For all study agencies, pain severity was documented in 13%, 19%, and 22% of patient records both before and after protocol changes. There was a difference in intranasal fentanyl administration rates before (27%) and after (17%) protocol changes (p = 0.02). Conclusion: The proportion of injured children who receive prehospital opioid analgesia remains suboptimal despite implementation of best practice recommendations. Frequency of pain severity assessment of injured children is low. Intranasal fentanyl administration may be an underutilized modality of prehospital opiate administration.

Comparative analysis of different methods of anesthesia in patients with acute pancreatitis using pain scales

Aim. To conduct a comparative analysis of used anesthesia methods in patients with acute pancreatitis in intensive care units settings using pain scales.Methods. Depending on the anesthesia type, 44 patients with acute pancreatitis were divided into three groups: the first group received intramuscular injections of nonsteroidal anti-inflammatory drugs and spasmolytics, the second group - intramuscular injections of non-steroidal anti-inflammatory drugs and opioid analgesics, the third group - epidural anesthesia with local anesthetics. Comparative analysis of pain character, intensity was conducted, its dynamics in patients of all groups amid anesthesia was evaluated using a visual analogue scale, verbal rating scale, verbal descriptor scale, McGill pain questionnaire.Results. Baseline pain intensity in patients of all groups was high. Patients estimated this pain as «very strong». The time and the level of pain intensity reduction for various anesthesia types had differences. Pain syndrome was eliminated slower in patients of the second group. By the end of the 1st day, patients of this group continued to complain of «strong» pain. Pain intensity decreased only on the 2nd day - patients reported «moderate» pain. Pain syndrome was not completely eliminated in these patients for 2 days of anesthesia. 97.7% of patients reported that the visual analogue scale is the most acceptable pain assessment scale for them.Conclusion. In patients with acute pancreatitis, the most optimal anesthesia types are intramuscular nonsteroidal anti-inflammatory drugs with spasmolytics and prolonged epidural anesthesia with local anesthetics; intramuscular administration of opioid analgesics with non-steroidal anti-inflammatory drugs is less effective in relieving pain.

Clinical outcomes of cardiac arrest patients according to opioid use history

PurposeOpioid analgesics are potent respiratory depressants. The purpose of this study was to describe the effects of opioids administered within 24hours before cardiac arrest on clinical outcomes. Materials and methodsWe retrospectively collected the cardiac arrest data of noncancer patients who were admitted to the general ward of Asan Medical Center from January 2008 to August 2012. We investigated the proportion of these patients who received opioids within 24hours of a cardiac arrest event, as well as the cardiac arrest characteristics, survival rates, and opioid administration patterns. ResultsOf the 193 patients identified, 58 (30%) had been administered opioids within the previous 24hours (the opioid group), whereas the remaining 135 (70%) had not been administered opioids (the nonopioid group). The survival rate did not differ significantly between these 2 groups. In the opioid group, as-needed opioid administration was associated with a lower 24-hour survival rate than regular opioid administration (9 [33.3%] of 27 patients vs 20 [64.5%] of 31 patients; P=.030). In multivariate logistic regression analysis, as-needed opioid administration was negatively associated with 24-hour survival. ConclusionsOpioid administration within 24hours before cardiac arrest per se was not associated with adverse outcomes. However, administration of opioid analgesics on an as-needed basis was associated with poorer survival outcomes than regular dosing. Greater attention should be paid to patients who receive as-needed opioid administration in the general ward.

Opioid Drugs in Patients With Liver Disease: A Systematic Review.

ContextThe liver, one of the most important organs of the body, is known to be responsible for several functions. The functional contribution of the liver to the metabolism of carbohydrates, protein, drugs and toxins, fats and cholesterol and many other biological processes are still unknown. Liver disorders are classified into two types: acute and chronic. Different drugs are used in liver diseases to treat and control pain. Most pain relief medications such as opioids are metabolized via the liver; therefore, the adverse reactions of drugs are probably higher for patients with liver disease. The current study aimed to evaluate the effects of opioid drugs on patients with liver disease; therefore, it is necessary to select suitable opioids for such patients.Evidence AcquisitionThis review was written by referring to research literature including 70 articles and four textbooks published from 1958 to 2015 on various reputable sites. Searches were carried out on the key phrases of narcotic pain relievers (opioids), acute and chronic hepatic failure, opioid adverse drug reactions, drug-induced liver injury (DILI) and other similar keywords. References included a variety of research papers (descriptive and analytical), intervention and review articles.ResultsIn patients with liver disease, administration of opioid analgesics should be observed, accurately. As a general rule, lower doses of drugs should be administered at regular intervals based on the signs of drug accumulation. Secondly, the interactions of opioid drugs with different levels of substrates of the P450 cytochrome enzyme should be considered.ConclusionsPain management in patients with liver dysfunction is always challenging to physicians because of the adverse reactions of drugs, especially opioids. Opioids should be used cautiously since they can cause sedation, constipation and sudden encephalopathy effects. Since the clearance of these drugs in patients with hepatic insufficiency is decreased, the initial dose must be decreased, the intervals between doses should be increased and some patients need to be continuously assessed.

Procyanidins alleviates morphine tolerance by inhibiting activation of NLRP3 inflammasome in microglia.

BackgroundThe development of antinociceptive tolerance following repetitive administration of opioid analgesics significantly hinders their clinical use. Evidence has accumulated indicating that microglia within the spinal cord plays a critical role in morphine tolerance. The inhibitor of microglia is effective to attenuate the tolerance; however, the mechanism is not fully understood. Our present study investigated the effects and possible mechanism of a natural product procyanidins in improving morphine tolerance via its specific inhibition on NOD-like receptor protein3 (NLRP3) inflammasome in microglia.MethodsCD-1 mice were used for tail-flick test to evaluate the degree of pain. The microglial cell line BV-2 was used to investigate the effects and the mechanism of procyanidins. Reactive oxygen species (ROS) produced from BV-2 cells was evaluated by flow cytometry. Cell signaling was measured by western blot assay and immunofluorescence assay.ResultsCo-administration of procyanidins with morphine potentiated its antinociception effect and attenuated the development of acute and chronic morphine tolerance. Procyanidins also inhibited morphine-induced increase of interleukin-1β and activation of NOD-like receptor protein3 (NLRP3) inflammasome. Furthermore, procyanidins decreased the phosphorylation of p38 mitogen-activated protein kinase, inhibited the translocation of nuclear factor-κB (NF-κB), and suppressed the level of reactive oxygen species in microglia.ConclusionsProcyanidins suppresses morphine-induced activation of NLRP3 inflammasome and inflammatory responses in microglia, and thus resulting in significant attenuation of morphine antinociceptive tolerance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0520-z) contains supplementary material, which is available to authorized users.

Prehospital Opioid Administration in the Emergency Care of Injured Children

Objective: Prior studies have identified provider and system characteristics that impede pain management in children, but no studies have investigated the effect of changing these characteristics on prehospital opioid analgesia. Our objectives were to determine: 1) the frequency of opioid analgesia and pain score documentation among prehospital pediatric patients after system wide changes to improve pain treatment, and 2) if older age, longer transport times, the presence of vascular access and pain score documentation were associated with increased prehospital administration of opioid analgesia in children. Methods: This was a retrospective cross-sectional study of pediatric patients aged 3–18 years assessed by a single EMS system between October 1, 2011 and September 30, 2013. Prior to October 2011, the EMS system had implemented 3 changes to improve pain treatment: (1) training on age appropriate pain scales, (2) protocol changes to allow opioid analgesia without contacting medical control, and (3) the introduction of intranasal fentanyl. All patients with working assessments of blunt, penetrating, lacerating, and/or burn trauma were included. We used descriptive statistics to determine the frequency of pain score documentation and opioid analgesia administration and logistic regression to determine the association of age, transport time, and the presence of intravenous access with opioid analgesia administration. Results: Of the 1,368 eligible children, 336 (25%) had a documented pain score. Eleven percent (130/1204) of children without documented contraindications to opioid administration received opioids. Of the children with no documented pain score and no protocol exclusions, 9% (81/929) received opioid analgesia, whereas 18% (49/275) with a documented pain score ≥4 and no protocol exclusions received opioids. Multivariate analysis revealed that vascular access (OR = 11.89; 95% CI: 7.33–19.29), longer patient transport time (OR = 1.07; 95% CI: 1.04–1.11), age (OR 0.93; 95% CI: 0.88–0.98) and pain score documentation (OR 2.23; 95% CI: 1.40–3.55) were associated with opioid analgesia. Conclusions: Despite implementation of several best practice recommendations to improve prehospital pain treatment, few children have a documented pain score and even fewer receive opioid analgesia. Children with longer transport times, successful IV placement, and/or documentation of pain score(s) were more likely to receive prehospital analgesia.