Postoperative analgesic options after spine surgery: finding the optimal treatment strategies.

INTRODUCTION: Spine surgery is one of the most common types of surgeries performed in the United States; however, managing postoperative pain following spine surgery has proven to be challenging. Patients with spine pathologies have higher incidences of chronic pain and resultant opioid use and potential for tolerance. Implementing a multimodal plan for postoperative analgesia after spine surgery can lead to enhanced recovery and outcomes. AREAS COVERED: This review presents several options for analgesia following spine surgery with an emphasis on multimodal techniques to best aid this specific patient population. In addition to traditional therapeutics, such as acetaminophen, non-steroidal anti-inflammatory medications, and opioids, we discuss intrathecal morphine administration and emerging regional anesthesia techniques. EXPERT OPINION: Several adjuncts to improve analgesia following spine surgery are efficacious in the postoperative period. Intrathecal morphine provides sustained analgesia and can be instilled intraoperatively by the surgical team under direct visualization. Local anesthetics deposited under ultrasound guidance by an anesthesiologist trained in regional techniques also provide the opportunity for single injections or continuous analgesia via an indwelling catheter.

Clinical Diagnosis and Treatment of Chronic Pain.

More than 600 million people globally are estimated to be living with chronic pain. It is one of the most common complaints seen in an outpatient setting, with over half of patients complaining of pain during a visit. Failure to properly diagnose and manage chronic pain is associated with substantial morbidity and mortality, especially when opioids are involved. Furthermore, it is a tremendous financial strain on the healthcare system, as over USD 100 billion is spent yearly in the United States on healthcare costs related to pain management and opioids. This exceeds the costs of diabetes, heart disease, and cancer-related care combined. Being able to properly diagnose, manage, and treat chronic pain conditions can substantially lower morbidity, mortality, and healthcare costs in the United States. This review will outline the current definitions, biopsychosocial model, subclassifications, somatosensory assessments, imaging, clinical prediction models, and treatment modalities associated with chronic pain.

Incidence of postoperative opioid-induced respiratory depression episodes in patients on room air or supplemental oxygen: a post-hoc analysis of the PRODIGY trial.

BACKGROUND: Supplemental oxygen (SO) potentiates opioid-induced respiratory depression (OIRD) in experiments on healthy volunteers. Our objective was to examine the relationship between SO and OIRD in patients on surgical units. METHODS: This post-hoc analysis utilized a portion of the observational PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial dataset (202 patients, two trial sites), which involved blinded continuous pulse oximetry and capnography monitoring of postsurgical patients on surgical units. OIRD incidence was determined for patients receiving room air (RA), intermittent SO, or continuous SO. Generalized estimating equation (GEE) models, with a Poisson distribution, a log-link function and time of exposure as offset, were used to compare the incidence of OIRD when patients were receiving SO vs RA. RESULTS: Within the analysis cohort, 74 patients were always on RA, 88 on intermittent and 40 on continuous SO. Compared with when on RA, when receiving SO patients had a higher risk for all OIRD episodes (incidence rate ratio [IRR] 2.7, 95% confidence interval [CI] 1.4-5.1), apnea episodes (IRR 2.8, 95% CI 1.5-5.2), and bradypnea episodes (IRR 3.0, 95% CI 1.2-7.9). Patients with high or intermediate PRODIGY scores had higher IRRs of OIRD episodes when receiving SO, compared with RA (IRR 4.5, 95% CI 2.2-9.6 and IRR 2.3, 95% CI 1.1-4.9, for high and intermediate scores, respectively). CONCLUSIONS: Despite oxygen desaturation events not differing between SO and RA, SO may clinically promote OIRD. Clinicians should be aware that postoperative patients receiving SO therapy remain at increased risk for apnea and bradypnea. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02811302, registered June 23, 2016.

The validity and applications of the analgesia nociception index: a narrative review.

Pain refers to the subjective, unpleasant experience that is related to illness or injury. In contrast to pain, nociception refers to the physiological neural processing of noxious stimuli, such as intra-operative surgical stimuli. One novel device, the Analgesia Nociception Index (ANI), aims to objectively measure intra-operative nociception by analyzing the heart rate variability in patients undergoing surgery. Through this method of nociceptive monitoring, the ANI device aims to provide an objective, continuous evaluation of patient comfort levels and allow anesthesiologists to better manage surgical stress and patient analgesia, perhaps with even better efficacy than current practices used to assess nociception. Additionally, ANI may have clinical application in settings outside of the operating room, such as in the intensive care unit. In this narrative review, we compiled and summarized the findings of many studies that have investigated ANI's validity and applications in different clinical settings. Currently, the literature appears mostly supportive of ANI's ability to detect nociception in both surgical and non-surgical settings. However, the ability for ANI to provide clinical benefits, such as decreased intra-operative opioid use, post-operative opioid use, and post-operative pain compared to standard practices appear controversial. Because of the wide variety of methodology, clinical settings, patient populations, and limitations in these studies, more investigation of ANI is needed before any firm conclusions can be drawn on its clinical benefits.

Frailty: the perioperative and anesthesia challenges of an emerging pandemic.

Frailty is a complex and multisystem biological process characterized by reductions in physiological reserve. It is an increasingly common phenomena in the surgical population, and significantly impacts postoperative recovery. In this review, we will discuss the pathophysiology of frailty, as well as preoperative, intraoperative, and postoperative considerations for frailty care. We will also discuss the different models of postoperative care, including enhanced recovery pathways, as well as elective critical care admission. With discoveries of new effective interventions, and advances in healthcare information technology, optimized pathways could be developed to provide the best care possible that meets the challenges of perioperative frailty.

Oliceridine for the Management of Moderate to Severe Acute Postoperative Pain: A Narrative Review.

Despite current advances in acute postoperative pain management, prevalence remains high. Inadequate treatment could lead to poor outcomes and even progression to chronic pain. Opioids have traditionally been the mainstay for treatment of moderate to severe acute pain. However, their use has been associated with opioid-related adverse events (ORAEs), such as respiratory depression, sedation, nausea, vomiting, pruritus, and decreased bowel motility. In addition, their liberal use has been implicated in the current opioid epidemic. As a result, there has been renewed interest in multimodal analgesia to target different mechanisms of action in order to achieve a synergistic effect and minimize opioid usage. Oliceridine is a novel mu-opioid receptor agonist that is part of a new class of biased ligands that selectively activate G-protein signaling and downregulate ß-arrestin recruitment. Since G-protein signaling has been associated with analgesia while ß-arrestin recruitment has been associated with ORAEs, there is potential for a wider therapeutic window. In this review, we will discuss the clinical evidence behind oliceridine and its potential role in acute postoperative pain management. We have systematically searched the PubMed database using the keywords oliceridine, olinvyk, and trv130. All articles identified were reviewed and evaluated, and all clinical trials were included.

[Zero Emissions. A shared responsibility. Gas capture and recycling project at the Cruces University Hospital (Spain).] / Emisiones Zero. Una responsabilidad compartida. Proyecto captura de gases y reciclado en el Hospital Universitario de Cruces.

OBJECTIVE: The use of volatile anesthetics plays an important role in the production of greenhouse gases and other environmental pollutants that negatively affect global health. Programs to reduce anesthesia contaminants have been shown to be effective and reduce costs. For this reason, we conducted a study to implementing a Zero Emissions Program for zero carbon dioxide emissions derived from anesthetic gases used in the operating room, as recommended by the Green Deal of the European Union by 2030 and be climate neutral in 2050, maintaining satisfaction and current clinical results. METHODS: A Zero Emissions Program was implemented within the Zero safety programs of the Cruces University Hospital in order to produce zero emissions of carbon dioxide derived from the anesthetic gases used in the operating rooms. The contribution of anesthetic gases to carbon dioxide production before and after implementation of program was determined. Data analysis was conducted descriptively to analyze program effectiveness. RESULTS: The implementation of a Zero Emissions Program allowed us to achieve a reduction in emissions to zero. CONCLUSIONS: Anesthesiologists must understand that minimizing our harmful impact on environmental health sustainability is not only desirable, but ethically necessary. A way to contribute to this ethical responsibility is Zero Emissions Programs which are effective in reducing emissions to zero, probably improving our impact on planet health.

OBJETIVO: El uso de anestésicos volátiles juega un papel importante en la producción de gases de efecto invernadero y otros contaminantes ambientales que afectan negativamente a la salud mundial. Se ha demostrado que los programas para reducir los contaminantes de la anestesia en el medio ambiente son eficaces y también reducen los costes. Por este motivo nos planteamos como objetivo implementar un Programa de Emisiones Zero para producir cero emisiones de dióxido de carbono derivados de los gases anestésicos utilizados en el quirófano, como recomienda el Pacto Verde de la Unión Europea, para 2030 y ser climáticamente neutros en 2050, manteniendo la satisfacción y los resultados clínicos actuales. METODOS: Se implementó un Programa de Emisiones Zero dentro de los programas Zero de seguridad del Hospital Universitario de Cruces (Barakaldo) con la finalidad de producir cero emisiones de dióxido de carbono derivado de los gases anestésicos utilizados en los quirófanos. Se determinó la contribución de los gases anestésicos a la producción de dióxido de carbono previo y posterior a la implementación del programa. El análisis de los datos se llevó a cabo de forma descriptiva para analizar la efectividad del programa. RESULTADOS: La implementación de un Programa de Emisiones de Zero nos permitió conseguir una disminución de las emisiones a cero. CONCLUSIONES: Los anestesiólogos debemos comprender que minimizar nuestro impacto nocivo en la sostenibilidad de la salud ambiental no es solo deseable, sino éticamente necesario. Una de las formas de contribuir con esta responsabilidad ética es con la implementación de Programas de Emisiones Zero que son eficaces en la reducción a cero de estas emisiones con lo que mejoraremos nuestro impacto en la salud del planeta.

Emisiones Zero. Una responsabilidad compartida. Proyecto captura de gases y reciclado en el Hospital Universitario de Cruces / Zero Emissions. A shared responsibility. Gas capture and recycling project at the Cruces University Hospital (Spain)

FUNDAMENTOS: El uso de anestésicos volátiles juega un papel importante en la producción de gases de efecto invernadero y otros contaminantes ambientales que afectan negativamente a la salud mundial. Se ha demostrado que los programas para reducir los contaminantes de la anestesia en el medio ambiente son eficaces y también reducen los costes. Por este motivo nos planteamos como objetivo implementar un Programa de Emisiones Zero para producir cero emisiones de dióxido de carbono derivados de los gases anestésicos utilizados en el quirófano, como recomienda el Pacto Verde de la Unión Europea, para 2030 y ser climáticamente neutros en 2050, manteniendo la satisfacción y los resultados clínicos actuales. MÉTODOS: Se implementó un Programa de Emisiones Zero dentro de los programas Zero de seguridad del Hospital Universitario de Cruces (Barakaldo) con la finalidad de producir cero emisiones de dióxido de carbono derivado de los gases anestésicos utilizados en los quirófanos. Se determinó la contribución de los gases anestésicos a la producción de dióxido de carbono previo y posterior a la implementación del programa. El análisis de los datos se llevó a cabo de forma descriptiva para analizar la efectividad del programa. RESULTADOS: La implementación de un Programa de Emisiones de Zero nos permitió conseguir una disminución de las emisiones a cero. CONCLUSIONES: Los anestesiólogos debemos comprender que minimizar nuestro impacto nocivo en la sostenibilidad de la salud ambiental no es solo deseable, sino éticamente necesario. Una de las formas de contribuir con esta responsabilidad ética es con la implementación de Programas de Emisiones Zero que son eficaces en la reducción a cero de estas emisiones con lo que mejoraremos nuestro impacto en la salud del planeta.(AU)

BACKGROUND: The use of volatile anesthetics plays an important role in the production of greenhouse gases and other environmental pollutants that negatively affect global health. Programs to reduce anesthesia contaminants have been shown to be effective and reduce costs. For this reason, we conducted a study to implementing a Zero Emissions Program for zero carbon dioxide emissions derived from anesthetic gases used in the operating room, as recommended by the Green Deal of the European Union by 2030 and be climate neutral in 2050, maintaining satisfaction and current clinical results. METHODS: A Zero Emissions Program was implemented within the Zero safety programs of the Cruces University Hospital in order to produce zero emissions of carbon dioxide derived from the anesthetic gases used in the operating rooms. The contribution of anesthetic gases to carbon dioxide production before and after implementation of program was determined. Data analysis was conducted descriptively to analyze program effectiveness. RESULTS: The implementation of a Zero Emissions Program allowed us to achieve a reduction in emissions to zero. CONCLUSIONS: Anesthesiologists must understand that minimizing our harmful impact on environmental health sustainability is not only desirable, but ethically necessary. A way to contribute to this ethical responsibility is Zero Emissions Programs which are effective in reducing emissions to zero, probably improving our impact on planet health.(AU)

Sugammadex versus neostigmine for neuromuscular blockade reversal in outpatient surgeries: A randomized controlled trial to evaluate efficacy and associated healthcare cost in an academic center.

Introduction: Neuromuscular blockade is an essential component of the general anesthesia as it allows for a better airway management and optimal surgical conditions. Despite significant reductions in extubation and OR readiness-for-discharge times have been associated with the use of sugammadex, the cost-effectiveness of this drug remains controversial. We aimed to compare the time to reach a train-of-four (TOF) response of ≥0.9 and operating room readiness for discharge in patients who received sugammadex for moderate neuromuscular blockade reversal when compared to neostigmine during outpatient surgeries under general anesthesia. Potential reduction in time for OR discharge readiness as a result of sugammadex use may compensate for the existing cost-gap between sugammadex and neostigmine. Methods: We conducted a single-center, randomized, double arm, open-label, prospective clinical trial involving adult patients undergoing outpatient surgeries under general anesthesia. Eligible subjects were randomized (1:1 ratio) into two groups to receive either sugammadex (Groups S), or neostigmine/glycopyrrolate (Group N) at the time of neuromuscular blockade reversal. The primary outcome was the time to reverse moderate rocuronium-induced neuromuscular blockade (TOF ratio ≥0.9) in both groups. In addition, post-anesthesia care unit (PACU)/hospital length of stay (LOS) and perioperative costs were compared among groups as secondary outcomes. Results: Thirty-seven subjects were included in our statistical analysis (Group S= 18 subjects and Group N= 19 subjects). The median time to reach a TOF ratio ≥0.9 was significantly reduced in Group S when compared to Group N (180 versus 540 seconds; p = 0.0052). PACU and hospital LOS were comparable among groups. Postoperative nausea and vomiting was the main adverse effect reported in Group S (22.2% versus 5.3% in Group N; p = 0.18), while urinary retention (10.5%) and shortness of breath (5.3%) were only experienced by some patients in Group N. Moreover, no statistical differences were found between groups regarding OR/anesthesia, PACU, and total admission costs. Discussion: Sugammadex use was associated with a significantly faster moderate neuromuscular blockade reversal. We found no evidence of increased perioperative costs associated with the use of sugammadex in patients undergoing outpatient surgeries in our academic institution. Clinical trial registration: [https://clinicaltrials.gov/] identifier number [NCT03579589].

Prospective multicenter study of heart rate variability with ANI monitor as predictor of mortality in critically ill patients with COVID-19.

The purpose of this study is to demonstrate that the most critically ill patients with COVID-19 have greater autonomic nervous system dysregulation and assessing the heart rate variability, allows us to predict severity and 30-day mortality. This was a multicentre, prospective, cohort study. Patients were divided into two groups depending on the 30-day mortality. The heart rate variability and more specifically the relative parasympathetic activity (ANIm), and the SDNN (Energy), were measured. To predict severity and mortality multivariate analyses of ANIm, Energy, SOFA score, and RASS scales were conducted. 112 patients were collected, the survival group (n = 55) and the deceased group (n = 57). The ANIm value was higher (p = 0.013) and the Energy was lower in the deceased group (p = 0.001); Higher Energy was correlated with higher survival days (p = 0.009), and a limit value of 0.31 s predicted mortalities with a sensitivity of 71.9% and a specificity of 74.5%. Autonomic nervous system and heart rate variability monitoring in critically ill patients with COVID-19 allows for predicting survival days and 30-day mortality through the Energy value. Those patients with greater severity and mortality showed higher sympathetic depletion with a predominance of relative parasympathetic activity.

Postoperative Nausea and Vomiting in Female Patients Undergoing Breast and Gynecological Surgery: A Narrative Review of Risk Factors and Prophylaxis.

Postoperative nausea and vomiting (PONV) have been widely studied as a multifactorial entity, being of female gender the strongest risk factor. Reported PONV incidence in female surgical populations is extremely variable among randomized clinical trials. In this narrative review, we intend to summarize the incidence, independent predictors, pharmacological and non-pharmacological interventions for PONV reported in recently published clinical trials carried out in female patients undergoing breast and gynecologic surgery, as well as the implications of the anesthetic agents on the incidence of PONV. A literature search of manuscripts describing PONV management in female surgical populations (breast surgery and gynecologic surgery) was carried out in PubMed, MEDLINE, and Embase databases. Postoperative nausea and vomiting incidence were highly variable in patients receiving placebo or no prophylaxis among RCTs whereas consistent results were observed in patients receiving 1 or 2 prophylactic interventions for PONV. Despite efforts made, a considerable number of female patients still experienced significant PONV. It is critical for the anesthesia provider to be aware that the coexistence of independent risk factors such as the level of sex hormones (pre- and postmenopausal), preoperative anxiety or depression, pharmacogenomic pleomorphisms, and ethnicity further enhances the probability of experiencing PONV in female patients. Future RCTs should closely assess the overall risk of PONV in female patients considering patient- and surgery-related factors, and the level of compliance with current guidelines for prevention and management of PONV.

Brain Prehabilitation for Oncologic Surgery.

PURPOSE OF REVIEW: This review aims to summarize the current research on postoperative cognitive complications, such as delirium and cognitive dysfunction. This includes discussion on preoperative preventive strategies, such as physical and nutritional prehabilitation as well as up-to-date information on neuroprehabilitation. RECENT FINDINGS: Current recommendations for prevention of postoperative delirium have focused on multicomponent interventions. The optimal composition of surgical prehabilitation programs targeting exercise and nutrition has not yet been established. The Neurobics Trial shows that cognitive prehabilitation improves cognitive reserve and may be a useful addition to multimodal surgical prehabilitation. Perioperative management of oncologic patients is often associated with a myriad of challenges, such as the management of tumor-related pathologies, adverse events from neoadjuvant therapy, and chronic metabolic and immunological changes associated with malignancy. In addition, oncologic patients are at increased risk of developing frailty, which adversely affects postoperative recovery and further cancer treatment. As a result, oncologic patients are at considerable risk of developing postoperative cognitive complications, such as delirium and cognitive dysfunction. In this review, we discuss the effect of prehabilitation on postoperative cognitive outcomes.

Brain Cancer Progression: A Retrospective Multicenter Comparison of Awake Craniotomy Versus General Anesthesia in High-grade Glioma Resection.

BACKGROUND: High-grade gliomas impose substantial morbidity and mortality due to rapid cancer progression and recurrence. Factors such as surgery, chemotherapy and radiotherapy remain the cornerstones for treatment of brain cancer and brain cancer research. The role of anesthetics on glioma progression is largely unknown. METHODS: This multicenter retrospective cohort study compared patients who underwent high-grade glioma resection with minimal sedation (awake craniotomy) and those who underwent craniotomy with general anesthesia (GA). Various perioperative factors, intraoperative and postoperative complications, and adjuvant treatment regimens were recorded. The primary outcome was progression-free survival (PFS); secondary outcomes were overall survival (OS), postoperative pain score, and length of hospital stay. RESULTS: A total of 891 patients were included; 79% received GA, and 21% underwent awake craniotomy. There was no difference in median PFS between awake craniotomy (0.54, 95% confidence interval [CI]: 0.45-0.65 y) and GA (0.53, 95% CI: 0.48-0.60 y) groups (hazard ratio 1.05; P <0.553). Median OS was significantly longer in the awake craniotomy (1.70, 95% CI: 1.30-2.32 y) compared with that in the GA (1.25, 95% CI: 1.15-1.37 y) group (hazard ratio 0.76; P <0.009) but this effect did not persist after controlling for other variables of interest. Median length of hospital stay was significantly shorter in the awake craniotomy group (2 [range: 0 to 76], interquartile range 3 d vs. 5 [0 to 98], interquartile range 5 for awake craniotomy and GA groups, respectively; P <0.001). Pain scores were comparable between groups. CONCLUSIONS: There was no difference in PFS and OS between patients who underwent surgical resection of high-grade glioma with minimal sedation (awake craniotomy) or GA. Further large prospective randomized controlled studies are needed to explore the role of anesthetics on glioma progression and patient survival.

Evaluating oliceridine as a treatment option for moderate to severe acute post-operative pain in adults.

INTRODUCTION: Despite the advances in regional anesthesia and non-opioid systemic analgesia, opioids remain the primary rescue analgesic for moderate to severe pain. However, the risks and side effects of opioid medications are well documented. Oliceridine is a novel opioid receptor agonist which is thought to have less risk of adverse events, such as postoperative nausea and vomiting (PONV) and respiratory depression. AREAS COVERED: In this review, the authors discuss the limitations of the current opioid and non-opioid analgesic options. They also review the pharmacokinetics of oliceridine, its analgesic efficacy, and risk of adverse events; and its added clinical value in managing moderate to severe pain. EXPERT OPINION: Despite the advances in regional anesthesia and multimodal systemic analgesia, opioid free analgesia is only feasible in selected procedures and patients. Oliceridine is effective in the management of moderate to severe pain and appears to be associated with lower risk of nausea and vomiting. The risk of sedation and respiratory depression associated with oliceridine will require further study. The availability of an opioid agonist with a better side effect profile could potentially change the current paradigm of opioid avoidance in postoperative pain management.

Frequency and Temporal Distribution of Postoperative Respiratory Depressive Events.

BACKGROUND: The frequency and temporal distribution of postoperative respiratory depression (RD) events are not completely understood. This study determined the temporal distribution and frequency of RD episodes in postsurgical patients continuously monitored by bedside capnography and pulse oximetry. METHODS: This was a post hoc study of a subset of postsurgical patients enrolled in The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial from 2 sites in the United States. These patients had undergone continuous bedside monitoring on general care wards. These data were adjudicated for potential RD episodes. The number of RD episodes per patient and the time of each RD episode were determined. The first RD episode experienced by a patient was classified as an "initial" episode, and the initial and all subsequent RD episodes experienced by a patient were classified as "all" episodes. A PRODIGY risk score was calculated. RESULTS: Data analyzed from 250 patients contained 2539 RD episodes in 155 (62.0%, 95% confidence interval, 55.7-68.0) patients with median 2 [0-8], range of 0-545 RD episodes per patient, with a PRODIGY risk score distribution of 100 (40.0%) low, 79 (31.6%) intermediate, 70 (28.0%) high (missing data from 1 patient). Median time to the initial RD episode was 8.8 [5.1-18.0] hours postoperatively. There was a peak occurrence of initial RD events between 14:00 and 20:00 on the day of surgery, and these were associated with a large number of subsequent events in the same timeframe. The peak time of all RD episodes occurred from 02:00 to 06:00. Patients with high PRODIGY risk scores had higher incidence and greater number of RD episodes per patient (P < .001, overall comparisons between groups for both incidence [χ2] and number of episodes [Kruskal-Wallis test]). CONCLUSIONS: Continuous monitoring of surgical patients demonstrates that RD episodes are common, and risk increases with higher PRODIGY scores. In this patient cohort, the rate of initial RD episodes peaked in the afternoon to early evening, while peak rate of all RD episodes occurred in early morning. Further, among patients with RD episodes, the number of episodes increased with higher PRODIGY scores.

Opioid-induced respiratory depression increases hospital costs and length of stay in patients recovering on the general care floor.

BACKGROUND: Opioid-induced respiratory depression is common on the general care floor. However, the clinical and economic burden of respiratory depression is not well-described. The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial created a prediction tool to identify patients at risk of respiratory depression. The purpose of this retrospective sub-analysis was to examine healthcare utilization and hospital cost associated with respiratory depression. METHODS: One thousand three hundred thirty-five patients (N = 769 United States patients) enrolled in the PRODIGY trial received parenteral opioids and underwent continuous capnography and pulse oximetry monitoring. Cost data was retrospectively collected for 420 United States patients. Differences in healthcare utilization and costs between patients with and without ≥1 respiratory depression episode were determined. The impact of respiratory depression on hospital cost per patient was evaluated using a propensity weighted generalized linear model. RESULTS: Patients with ≥1 respiratory depression episode had a longer length of stay (6.4 ± 7.8 days vs 5.0 ± 4.3 days, p = 0.009) and higher hospital cost ($21,892 ± $11,540 vs $18,206 ± $10,864, p = 0.002) compared to patients without respiratory depression. Patients at high risk for respiratory depression, determined using the PRODIGY risk prediction tool, who had ≥1 respiratory depression episode had higher hospital costs compared to high risk patients without respiratory depression ($21,948 ± $9128 vs $18,474 ± $9767, p = 0.0495). Propensity weighted analysis identified 17% higher costs for patients with ≥1 respiratory depression episode (p = 0.007). Length of stay significantly increased total cost, with cost increasing exponentially for patients with ≥1 respiratory depression episode as length of stay increased. CONCLUSIONS: Respiratory depression on the general care floor is associated with a significantly longer length of stay and increased hospital costs. Early identification of patients at risk for respiratory depression, along with early proactive intervention, may reduce the incidence of respiratory depression and its associated clinical and economic burden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02811302 .

Safety of treatment options available for postoperative pain.

IntroductionPostoperative pain is one of the most common adverse events after surgery and has been shown to increase the risk of other complications. On the other hand, liberal opioid use in the perioperative period is also associated with risk of adverse events. The current consensus is therefore to provide multimodal, opioid minimizing analgesia after surgery.Areas CoveredIn this review, we will discuss the benefits and risks associated with non-opioid analgesics, including non-steroidal anti-inflammatory drugs, gabapentinoids, ketamine, α-2 agonists, and corticosteroids. In addition, we will discuss the general and block-specific risks associated with regional anesthestic techniques.Expert OpinionAdverse events associated with non-opioid analgesics are rare outside their specific contraindicated patient groups, especially when dosed appropriately. α-2 agonists can cause transient hypotension and bradycardia, and gabapentinoids may cause sedation in higher risk patient populations. Regional anesthesia techniques are generally safe when done by an experienced practitioner. We therefore encourage the development of standardized multimodal analgesic protocols, which may facilitate opioid minimization and lead to better patient outcomes.

Low Incidence of Opioid-Induced Respiratory Depression Observed with Oliceridine Regardless of Age or Body Mass Index: Exploratory Analysis from a Phase 3 Open-Label Trial in Postsurgical Pain.

INTRODUCTION: Advanced age and obesity are reported to increase the risk of opioid-induced respiratory depression (OIRD). Oliceridine, an intravenous opioid, is a G-protein-biased agonist at the µ-opioid receptor that may provide improved safety. The recent phase 3 ATHENA open-label, multicenter study evaluated postoperative use of oliceridine in patients with moderate-to-severe acute pain. This exploratory analysis of the ATHENA data examined the incidence of OIRD in older (≥ 65 years) and/or obese (BMI ≥ 30 kg/m2) patients and analyzed risk factors of OIRD. METHODS: Patients aged ≥ 18 years with a score ≥ 4 on an 11-point numeric pain rating scale (NPRS) received IV oliceridine as needed via bolus dosing and/or patient-controlled analgesia (PCA). OIRD occurring within 48 h of last dose of oliceridine was defined using two established definitions: (1) naloxone use, (2) respiratory rate < 10 breaths per minute and/or oxygen saturation < 90%. RESULTS: A total of 724 surgical patients with a mean age of 54.5 ± 15.9 years and a mean NRS score of 6.2 ± 2.1 were included in this analysis; 33.3% (241/724) were ≥ 65 years of age and 46.3% (335/724) had BMI (body mass index) ≥ 30 kg/m2. The overall OIRD incidence was 13.7% with no patients requiring naloxone. The OIRD incidence was similar in the elderly and younger adults' cohorts [10.8 vs. 15.1%, OR 0.68 (0.42, 1.1), p = 0.11], and in obese and non-obese groups [14.0 vs. 13.4%, OR 1.06 (0.69, 1.62), p = 0.80]. In patients that were both elderly and obese (n = 120), the incidence was 10.8%. The multivariate analysis identified baseline NRS ≥ 6 [OR 1.6 (1.0, 2.4), p = 0.0499], PCA administration [OR 1.9 (1.2, 3.1), p = 0.005], and concomitant use of benzodiazepines and/or gabapentinoids [OR 1.6 (1.0, 2.6), p = 0.045], as being associated with OIRD. CONCLUSIONS: Postoperative oliceridine use in patients with advanced age and/or increased BMI was not associated with increased risk of OIRD.

Postoperative opioid administration characteristics associated with opioid-induced respiratory depression: Results from the PRODIGY trial.

STUDY OBJECTIVE: Opioid administration for pain in general care floor patients remains common, and can lead to adverse outcomes, including respiratory compromise. The PRODIGY trial found that among ward patients receiving parenteral opioids, 46% experienced ≥1 respiratory depression episode. The objective of this analysis was to evaluate the geographic differences of opioid administration and examine the association between opioid administration characteristics and the occurrence of respiratory depression. DESIGN: Prospective observational trial. SETTING: 16 general care medical and surgical wards in Asia, Europe, and the United States. PATIENTS: 1335 patients receiving parenteral opioids. INTERVENTIONS: Blinded, alarm-silenced continuous capnography and pulse oximetry monitoring. MEASUREMENTS: Opioid-induced respiratory depression, defined as respiratory rate ≤ 5 bpm, SpO2 ≤ 85%, or ETCO2 ≤ 15 or ≥ 60 mmHg for ≥3 min; apnea episode lasting >30 s; or any respiratory opioid-related adverse event. RESULTS: Across all patients, 58% received only long-acting opioids, 16% received only short-acting (<3 h) opioids, and 21% received a combination of short- and long-acting (≥3 h) opioids. The type and median total morphine milligram equivalent (MME) of opioid administered varied significantly by region, with 31.5 (12.5-76.7) MME, 31.0 (6.2-99.0) MME, and 7.2 (1.7-18.7) MME in the United States, Europe, and Asia, respectively (p < 0.001). Considering only postoperative opioids, 54% (N = 119/220) and 45% (N = 347/779) of patients receiving only short-acting opioids or only long-acting opioids experienced ≥1 episode of opioid-induced respiratory depression, respectively. Multivariable analysis identified post-procedure tramadol (OR 0.62, 95% CI 0.424-0.905, p = 0.0133) and post-procedure epidural opioids (OR 0.485, 95% CI 0.322-0.731, p = 0.0005) being associated with a significant reduction in opioid-induced respiratory depression. CONCLUSIONS: Despite varying opioid administration characteristics between Asia, Europe, and the United States, opioid-induced respiratory depression remains a common global problem on general care medical and surgical wards. While the use of post-procedure tramadol or post-procedure epidural opioids may reduce the incidence of respiratory depression, continuous monitoring is also necessary to ensure patient safety when receiving postoperative opioids. REGISTRATION NUMBER: www.clinicaltrials.gov, ID: NCT02811302.