This review provides an overview of the clinical issue of poorly controlled postoperative pain and therapeutic approaches that may help to address this common unresolved health-care challenge. ...Postoperative pain is not adequately managed in greater than 80% of patients in the US, although rates vary depending on such factors as type of surgery performed, analgesic/anesthetic intervention used, and time elapsed after surgery. Poorly controlled acute postoperative pain is associated with increased morbidity, functional and quality-of-life impairment, delayed recovery time, prolonged duration of opioid use, and higher health-care costs. In addition, the presence and intensity of acute pain during or after surgery is predictive of the development of chronic pain. More effective analgesic/anesthetic measures in the perioperative period are needed to prevent the progression to persistent pain. Although clinical findings are inconsistent, some studies of local anesthetics and nonopioid analgesics have suggested potential benefits as preventive interventions. Conventional opioids remain the standard of care for the management of acute postoperative pain; however, the risk of opioid-related adverse events can limit optimal dosing for analgesia, leading to poorly controlled acute postoperative pain. Several new opioids have been developed that modulate μ-receptor activity by selectively engaging intracellular pathways associated with analgesia and not those associated with adverse events, creating a wider therapeutic window than unselective conventional opioids. In clinical studies, oliceridine (TRV130), a novel μ-receptor G-protein pathway-selective modulator, produced rapid postoperative analgesia with reduced prevalence of adverse events versus morphine.
Abstract
Background:
Diclofenac is a proven, commonly prescribed nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory, and antipyretic properties, and has been shown to ...be effective in treating a variety of acute and chronic pain and inflammatory conditions. As with all NSAIDs, diclofenac exerts its action via inhibition of prostaglandin synthesis by inhibiting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) with relative equipotency. However, extensive research shows the pharmacologic activity of diclofenac goes beyond COX inhibition, and includes multimodal and, in some instances, novel mechanisms of action (MOA).
Data sources:
Literature retrieval was performed through PubMed/MEDLINE (through May 2009) using combinations of the terms diclofenac, NSAID, mechanism of action, COX-1, COX-2, and pharmacology. Reference citations resulting from publications identified in the literature search were reviewed when appropriate.
Methods:
This article reviews the established, putative, and emerging MOAs of diclofenac; compares the drug’s pharmacologic and pharmacodynamic properties with other NSAIDs to delineate its potentially unique qualities; hypothesizes why it has been chosen for further recent formulation enhancement; and evaluates the potential effect of its MOA characteristics on safety.
Discussion:
Research suggests diclofenac can inhibit the thromboxane-prostanoid receptor, affect arachidonic acid release and uptake, inhibit lipoxygenase enzymes, and activate the nitric oxide-cGMP antinociceptive pathway. Other novel MOAs may include the inhibition of substrate P, inhibition of peroxisome proliferator activated receptor gamma (PPARγ), blockage of acid-sensing ion channels, alteration of interleukin-6 production, and inhibition of N-methyl-D-aspartate (NMDA) receptor hyperalgesia. The review was not designed to compare MOAs of diclofenac with other NSAIDs. Additionally, as the highlighted putative and emerging MOAs do not have clinical data to demonstrate that these models are correct, further research is necessary to ascertain if the proposed pathways will translate into clinical benefits. The diversity in diclofenac’s MOA may suggest the potential for a relatively more favorable profile compared with other NSAIDs.
Knowledge of postoperative nausea and vomiting (PONV) risk factors allows anesthesiologists to optimize the use of prophylactic regimens. Modern PONV risk research began in the 1990s with publication ...of studies using logistic regression analysis to simultaneously identify multiple independent PONV predictors and publication of meta-analyses and systematic reviews. This literature shows that female gender post-puberty, nonsmoking status, history of PONV or motion sickness, childhood after infancy and younger adulthood, increasing duration of surgery, and use of volatile anesthetics, nitrous oxide, large-dose neostigmine, or intraoperative or postoperative opioids are well established PONV risk factors. Possible risk factors include history of migraine, history of PONV or motion sickness in a child’s parent or sibling, better ASA physical status, intense preoperative anxiety, certain ethnicities or surgery types, decreased perioperative fluids, crystalloid versus colloid administration, increasing duration of anesthesia, general versus regional anesthesia or sedation, balanced versus total IV anesthesia, and use of longer-acting versus shorter-acting opioids. Early-phase menstruation, obesity and lack of supplemental oxygen are disproved risk factors. Current risk scoring systems have ∼55%–80% accuracy in predicting which patient groups will suffer PONV. Further research examining genetic and under-investigated clinical patient characteristics as potential risk factors, and involving outpatients and children, should improve predictive systems.
Perioperative malnutrition has proven to be challenging to define, diagnose, and treat. Despite these challenges, it is well known that suboptimal nutritional status is a strong independent predictor ...of poor postoperative outcomes. Although perioperative caregivers consistently express recognition of the importance of nutrition screening and optimization in the perioperative period, implementation of evidence-based perioperative nutrition guidelines and pathways in the United States has been quite limited and needs to be addressed in surgery-focused recommendations. The second Perioperative Quality Initiative brought together a group of international experts with the objective of providing consensus recommendations on this important topic with the goal of (1) developing guidelines for screening of nutritional status to identify patients at risk for adverse outcomes due to malnutrition; (2) address optimal methods of providing nutritional support and optimizing nutrition status preoperatively; and (3) identifying when and how to optimize nutrition delivery in the postoperative period. Discussion led to strong recommendations for implementation of routine preoperative nutrition screening to identify patients in need of preoperative nutrition optimization. Postoperatively, nutrition delivery should be restarted immediately after surgery. The key role of oral nutrition supplements, enteral nutrition, and parenteral nutrition (implemented in that order) in most perioperative patients was advocated for with protein delivery being more important than total calorie delivery. Finally, the role of often-inadequate nutrition intake in the posthospital setting was discussed, and the role of postdischarge oral nutrition supplements was emphasized.
This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations. The guidelines ...are established by an international panel of experts under the auspices of the American Society of Enhanced Recovery and Society for Ambulatory Anesthesia based on a comprehensive search and review of literature up to September 2019. The guidelines provide recommendation on identifying high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatment of PONV as well as recommendations for the institutional implementation of a PONV protocol. In addition, the current guidelines focus on the evidence for newer drugs (eg, second-generation 5-hydroxytryptamine 3 5-HT3 receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and dopamine antagonists), discussion regarding the use of general multimodal PONV prophylaxis, and PONV management as part of enhanced recovery pathways. This set of guidelines have been endorsed by 23 professional societies and organizations from different disciplines (Appendix 1).Guidelines currently available include the 3 iterations of the consensus guideline we previously published, which was last updated 6 years ago; a guideline published by American Society of Health System Pharmacists in 1999; a brief discussion on PONV management as part of a comprehensive postoperative care guidelines; focused guidelines published by the Society of Obstetricians and Gynecologists of Canada, the Association of Paediatric Anaesthetists of Great Britain & Ireland and the Association of Perianesthesia Nursing; and several guidelines published in other languages.The current guideline was developed to provide perioperative practitioners with a comprehensive and up-to-date, evidence-based guidance on the risk stratification, prevention, and treatment of PONV in both adults and children. The guideline also provides guidance on the management of PONV within enhanced recovery pathways.The previous consensus guideline was published 6 years ago with a literature search updated to October 2011. Several guidelines, which have been published since, are either limited to a specific populations or do not address all aspects of PONV management. The current guideline was developed based on a systematic review of the literature published up through September 2019. This includes recent studies of newer pharmacological agents such as the second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, a dopamine antagonist, neurokinin 1 (NK1) receptor antagonists as well as several novel combination therapies. In addition, it also contains an evidence-based discussion on the management of PONV in enhanced recovery pathways. We have also discussed the implementation of a general multimodal PONV prophylaxis in all at-risk surgical patients based on the consensus of the expert panel.
Opioid induced respiratory depression is a known cause of preventable death in hospitals. Medications with sedative properties additionally potentiate opioid-induced respiratory and sedative effects, ...thereby elevating the risk for adverse events. The goal of this study was to determine what specific factors increase the risk of in-hospital cardiopulmonary and respiratory arrest (CPRA) in medical and surgical patients on opioid and sedative therapy.
The present study analyzed 14,504,809 medical inpatient and 6,771,882 surgical inpatient discharges reported into the Premier database from 2008 to 2012. Patients were divided in four categories: on opioids; on sedatives; on both opioids and sedatives; and on neither opioids nor sedatives.
During hospital admission, 57% of all medical patients and 90% of all surgical patients were prescribed opioids, sedatives, or both. Surgical patients had a higher incidence of CPRA than medical patients (6.17 vs. 3.77 events per 1000 admissions; Relative Risk: 1.64 95%CI: 1.62-1.66; p<0.0001). Opioids and sedatives were found to be independent predictors of CPRA (adjusted OR of 2.24 95%CI: 2.18-2.29 for opioids and adjusted OR 1.80 95%CI: 1.75-1.85 for sedatives in medical patients, and adjusted OR of 1.12 95%CI: 1.07-1.16 for opioids and adjusted OR of 1.58 95%CI: 1.51-1.66 for sedatives in surgical patients), with the highest risk in groups who received both types of medications (adjusted OR of 3.83 95% CI: 3.74-3.92 in medical patients, and adjusted OR of 2.34 95% CI: 2.25-2.42 in surgical patients) compared with groups that received neither type of medication. The common risk factors of CPRA in medical and surgical patients receiving both opioids and sedatives were Hispanic origin, mild liver disease, obesity, and COPD. Additionally, medical and surgical groups had their own unique risk factors for CPRA when placed on opioid and sedative therapy.
Opioids and sedatives are independent and additive predictors of CPRA in both medical and surgical patients. Receiving both classes of medications further exacerbates the risk of CPRA for these patients. By identifying groups at risk among medical and surgical in-hospital patients, this study provides a step towards improving our understanding of how to use opioid and sedative medications safely, which may influence our treatment strategies and outcomes. More precise monitoring of selected high-risk patients may help prevent catastrophic cardiorespiratory complications from these medications. As a retrospective administrative database analysis, this study does not establish the causality or the temporality of the events but rather draws statistically significant associations between the clinical factors and outcomes.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Postoperative delirium is a geriatric syndrome that manifests as changes in cognition, attention, and levels of consciousness after surgery. It occurs in up to 50% of patients after major surgery and ...is associated with adverse outcomes, including increased hospital length of stay, higher cost of care, higher rates of institutionalization after discharge, and higher rates of readmission. Furthermore, it is associated with functional decline and cognitive impairments after surgery. As the age and medical complexity of our surgical population increases, practitioners need the skills to identify and prevent delirium in this high-risk population. Because delirium is a common and consequential postoperative complication, there has been an abundance of recent research focused on delirium, conducted by clinicians from a variety of specialties. There have also been several reviews and recommendation statements; however, these have not been based on robust evidence. The Sixth Perioperative Quality Initiative (POQI-6) consensus conference brought together a team of multidisciplinary experts to formally survey and evaluate the literature on postoperative delirium prevention and provide evidence-based recommendations using an iterative Delphi process and Grading of Recommendations Assessment, Development and Evaluation (GRADE) Criteria for evaluating biomedical literature.
Abstract
Objective:
During the past two decades, professional associations, accrediting bodies, and payors have made post-surgical pain treatment a high priority. In light of the disappointing ...findings in previous surveys, a survey was conducted to assess patient perceptions and characterize patient experiences/levels of satisfaction with post-surgical pain management.
Research design and methods:
Survey included a random sample of US adults who had undergone surgery within 5 years from the survey date. Participants were asked about their concerns before surgery, severity of perioperative pain, pain treatments, perceptions about post-surgical pain and pain medications, and satisfaction with treatments they received.
Results:
Of the 300 participants, ∼86% experienced pain after surgery; of these, 75% had moderate/extreme pain during the immediate post-surgical period, with 74% still experiencing these levels of pain after discharge. Post-surgical pain was the most prominent pre-surgical patient concern, and nearly half reported they had high/very high anxiety levels about pain before surgery. Approximately 88% received analgesic medications to manage pain; of these, 80% experienced adverse effects and 39% reported moderate/severe pain even after receiving their first dose.
Study limitations:
Key study limitations include the relatively small population size, potential for recall bias associated with the 14-month average time delay from surgery date to survey date, and the inability to account for influences of type of surgery and intraoperative anesthetic/analgesic use on survey results.
Conclusions:
Despite heightened awareness and clinical advancements in pain management, there has been little improvement in post-surgical analgesia as measured by this survey of post-surgical patients.
Potentially, perioperative regional anesthesia and analgesia (RA) could influence the outcomes of patients with cancer. The aim of this systematic review and meta-analysis was to evaluate the effects ...of perioperative RA on survival and cancer recurrence after oncologic surgery.
The authors searched computerized databases (from inception to December 2014) and reference lists and considered all studies comparing the effects of RA on cancer recurrence or overall survival with that of general anesthesia (GA). Risk estimates were pooled to determine the effects of RA on risks of cancer recurrence and mortality. Twenty eligible studies were included.
Perioperative RA use was associated with improved overall survival (Hazard ratio HR = 0.84, 95% CI, 0.75 - 0.94; I =41%), but not with reduced cancer recurrence (HR=0.91, 95% CI, 0.70 - 1.18; I=83%).
Our meta-analysis suggests that RA may improve overall survival but not reduce cancer recurrence after oncologic surgery.
Goal-directed hemodynamic therapy (GDHT) has been used in the clinical setting for years. However, the evidence for the beneficial effect of GDHT on postoperative recovery remains inconsistent. The ...aim of this systematic review and meta-analysis was to evaluate the effect of perioperative GDHT in comparison with conventional fluid therapy on postoperative recovery in adults undergoing major abdominal surgery.
Randomized controlled trials (RCTs) in which researchers evaluated the effect of perioperative use of GDHT on postoperative recovery in comparison with conventional fluid therapy following abdominal surgery in adults (i.e., >16 years) were considered. The effect sizes with 95% CIs were calculated.
Forty-five eligible RCTs were included. Perioperative GDHT was associated with a significant reduction in short-term mortality (risk ratio RR 0.75, 95% CI 0.61-0.91, p = 0.004, I
= 0), long-term mortality (RR 0.80, 95% CI 0.64-0.99, p = 0.04, I
= 4%), and overall complication rates (RR 0.76, 95% CI 0.68-0.85, p < 0.0001, I
= 38%). GDHT also facilitated gastrointestinal function recovery, as demonstrated by shortening the time to first flatus by 0.4 days (95% CI -0.72 to -0.08, p = 0.01, I
= 74%) and the time to toleration of oral diet by 0.74 days (95% CI -1.44 to -0.03, p < 0.0001, I
= 92%).
This systematic review of available evidence suggests that the use of perioperative GDHT may facilitate recovery in patients undergoing major abdominal surgery.
PDF
