Postoperative pain after different doses of remifentanil infusion during anaesthesia: a meta-analysis.

BACKGROUND: This meta-analysis aimed to explore the correlation between the different doses of remifentanil-based anaesthesia and postoperative pain in randomised trials. METHODS: The electronic databases including PubMed, Cochrane, clinical trial registries, and Google Scholar were searched up to November 2022 for randomised controlled trials (RCTs) that assessed the dose dependent efficacy of remifentanil for postoperative pain intensity and hyperalgesia. RESULTS: 31 studies involving 2019 patients were included for analysis. Compared with the high remifentanil dose administration, patients in low doses showed less postoperative pain intensity at 1-2 h (weighted mean differences (WMD): 0.60, 95% CI, 0.05 to 1.15), 3-8 h (WMD: 0.38, 95% CI, 0.00 to 0.75), 24 h (WMD: 0.26, 95% CI, 0.04 to 0.48) and 48 h (WMD: 0.32, 95% CI, 0.09 to 0.55). Remifentanil-free regimen failed to decrease the pain score at 24 h (WMD: 0.10, 95% CI, -0.10 to 0.30) and 48 h (WMD: 0.15, 95% CI, -0.22 to 0.52) in comparison with remifentanil-based anaesthesia. After excluding trials with high heterogeneity, the dose of the remifentanil regimen was closely correlated with the postoperative pain score (P=0.03). In addition, the dose of the remifentanil regimen was not associated with the incidence of postoperative nausea and vomiting (PONV) (P=0.37). CONCLUSIONS: Our meta-analysis reveals that the low dose of remifentanil infusion is recommendable for general anaesthesia maintenance. No evidence suggests that remifentanil-free regimen has superiority in reducing postoperative pain. Moreover, remifentanil doesn't have a dose dependent effect in initiating PONV. TRIAL REGISTRATION: The protocol of present study was registered with PROSPERO (CRD42022378360).

Opioid tapering and mental health crisis in older adults.

BACKGROUND: Opioid tapering and discontinuation have increased in recent years with the implementation of national prescribing guidelines. This study aimed to examine the relationship between opioid tapering velocity and mental health crisis events in older Medicare beneficiaries. METHODS: A nested case-control study was conducted using the 2012-2018, 5% national Medicare claims data. Older adults with chronic non-cancer pain (CNCP) who were receiving long-term opioid therapy (LTOT) were included in the study. Cases were defined as individuals experiencing mental health crisis events; controls were identified using incidence density sampling. The opioid tapering velocity was measured in the 120-day hazard period that yielded a monthly percentage of dose change. Conditional logistic regression was used to assess the relationship of interest. RESULTS: A total of 42 091 older adults with CNCP were eligible for the study. Cases (n = 952) were matched with controls in a 1:2 ratio based on age (±1 year) and time of cohort entry (±30 days). A higher percentage of controls (67.65%) were on steady dose compared with cases (59.03%). In the adjusted model, tapering (aOR = 1.36; 95% CI: 1.02-1.83), rapid tapering (aOR = 1.45; 95% CI: 1.11-1.91), and dose escalation (aOR = 1.78; 95% CI: 1.32-2.39) were significantly associated with the mental health crisis, compared with steady dose. CONCLUSION: Both opioid tapering and dose escalation are associated with mental health crisis events. Patient-driven and gradual dose tapering, as recommended by prescribing guidelines, should be promoted to prevent mental health crisis events among older adults on LTOT.

Tapentadol dependence through intravenous injection ('shooting') of crushed tablets associated with cutaneous pseudoallergic reactions.

Tapentadol is a synthetic opioid analgesic with a low risk of abuse and diversion. The rising trend of abuse of tapentadol is largely attributable to its intrinsic pharmacological profile and easy availability due to poor regulatory control. We report a case of intravenous injection of crushed tapentadol tablets that presented with cutaneous adverse drug reactions. Cutaneous adverse reactions are common in injection drug abuse, and clinical examination is a must to inspect the injection sites. Stringent regulatory measures are required to restrict the increasing abuse of tapentadol in India.

Put It in the Air? Nebulized Opioids in the Emergency Department.

The emergency department (ED) is a frequent utilizer of alternative routes of medication administration (e.g., intranasal) for a variety of indications. Over the last several years, investigations into the use of medications via the nebulization route have greatly increased, with varying degrees of efficacy identified. This route has multiple theoretical advantages. Medications affecting bronchopulmonary function or secretions can be administered directly to the site of action, possibly utilizing a lower dose and hence minimizing side effects. It is also possible to have a faster onset of action compared with other routes, given the enhanced surface area for absorption. One group of medications that has been explored via this route of administration, and is frequently administered in EDs across the nation, is opioids, most notably fentanyl, hydromorphone, and morphine. However multiple questions exist regarding the implementation of these therapies via this route, including efficacy, dosing, and the functional aspects of medication administration that are more complex than that of more traditional routes. The intent of this review is to explore the supporting literature behind the use of nebulized opioids, most specifically fentanyl, hydromorphone, and morphine, in the ED for the treatment of acute pain presentations and provide the most up-to-date guidance for practitioners.

Dexamethasone as additive of local infiltration analgesia reduces opioids consumption after simultaneous bilateral total hip or knee arthroplasty: a randomized controlled double-blind trial.

PURPOSE: A randomized controlled double-blind trial was conducted to evaluate the effects of adding dexamethasone to the local infiltration analgesia (LIA) mixture on frequency of patient controlled analgesia (PCA) and opioids consumption after simultaneous bilateral total hip or knee arthroplasty (THA or TKA). METHODS: 108 patients who received simultaneous bilateral THA or TKA were randomly divided into dexamethasone group and normal saline (NS) group. The main difference between two groups was whether or not dexamethasone was added to the LIA mixture. The main outcome was the cumulative consumption of opioids within 24 h. The secondary outcome were the total cumulative consumption of opioids during postoperative hospitalization, consumption of opioids drug for rescue analgesia, frequency of PCA, postoperative Visual Analogue Scale (VAS), and complications. RESULTS: Cumulative consumption of opioids in the 24 h was similar between two groups (P = 0.17). Total cumulative consumption of opioids in the dexamethasone group during postoperative hospitalization was significantly lower (P = 0.03). No significant difference in the consumption of opioids drug for rescue analgesia between two groups within 24 h, while the frequency of PCA was significantly different (P = 0.04). VAS of dexamethasone group and NS group were similar during postoperative hospitalization, while the incidence of postoperative nausea and vomiting (PONV) in dexamethasone group was lower than that in NS group. CONCLUSIONS: Adding dexamethasone to LIA in the simultaneous bilateral THA or TKA can effectively reduce the total cumulative consumption of opioids and the frequency of PCA, as well as reduce the incidence of PONV. Trial Registration The trial has been registered in the Chinese Clinical Trial Registry (Registration Number: ChiCTR2100042551, Date: 23/01/2021).

Reducing opioid prescribing after ambulatory breast reconstruction surgery.

BACKGROUND: The lack of evidence-based guidelines for postoperative opioid prescriptions following breast reconstruction contributes to a wide variation in prescribing practices and increases potential for misuse and abuse. METHODS: Between August and December 2019, women who underwent outpatient breast reconstruction were surveyed 7-10 days before (n = 97) and after (n = 101) implementing a standardized opioid prescription reduction initiative. We compared postoperative opioid use, pain control, and refills in both groups. Patient reported outcomes were compared using the BREAST-Q physical wellbeing of the chest domain and a novel symptom Recovery Tracker. RESULTS: Before changes in prescriptions, patients were prescribed a median of 30 pills and consumed three pills (interquartile range [IQR: 1,9]). After standardization, patients were prescribed eight pills and consumed three pills (IQR: 1,6). There was no evidence of a difference in the proportion of patients experiencing moderate to very severe pain on the Recovery Tracker or in the early BREAST-Q physical wellbeing of the chest scores (p = 0.8 and 0.3, respectively). CONCLUSION: Standardizing and reducing opioid prescriptions for patients undergoing reconstructive breast surgery is feasible and can significantly decrease the number of excess pills prescribed. The was no adverse impact on early physical wellbeing, although larger studies are needed to obtain further data.

Dose Changes for Long-term Opioid Patients Following a State Opioid Prescribing Policy.

BACKGROUND: In 2018, Nevada implemented opioid prescribing legislation (AB474) to support the uptake of CDC pain care guidelines. We studied the law's association with doses over threshold levels of morphine milligram equivalents (MMEs) and with time to dose increases and decreases, among long-term opioid patients. METHODS: A difference-in-difference study examined dosing changes across opioid prescription episodes (ie, prescriptions within 30 day and within the same dosing threshold). Patients with at least 120 days supply over 6 months in Nevada and Colorado Medicaid pharmacy claims were included. Using a logistic regression model, we compare the predicted probabilities that opioid episodes exceeded 50 MME before and after implementation of the law, in both states. Adjusted hazard ratios (aHR) from a gap time survival model estimated time to escalate above 50 MME among low-dose episodes (<50 MME), and time to de-escalate below 50 MME among high-dose episodes (≥50 MME). RESULTS: Among 453,577 episodes (74,292 patients), the Nevada law was associated with a 2.9% reduction in prescriptions over 50 MME (95% CI: -3.5, -2.3) compared with Colorado. While the law was also associated with slower escalation (Nevada: aHR = 0.75; 95% CI: 0.72, 0.77, Colorado: aHR = 1.04; 95% CI: 1.01, 1.06), it was also associated with slower de-escalation (Nevada: aHR = 0.87; 95% CI: 0.84, 0.89, Colorado: aHR = 0.97; 95% CI: 0.96, 0.99). CONCLUSIONS: Slower dose escalations, rather than faster dose de-escalation, likely explain post-law reductions in doses over 50 MME. Slower dose de-escalations may be due to longer days supply post-policy.

Predictors of frequent emergency department visits among hospitalized cancer patients: a comparative cohort study using integrated clinical and administrative data to improve care delivery.

BACKGROUND: Frequent emergency department (FED) visits by cancer patients represent a significant burden to the health system. This study identified determinants of FED in recently hospitalized cancer patients, with a particular focus on opioid use. METHODS: A prospective cohort discharged from surgical/medical units of the McGill University Health Centre was assembled. The outcome was FED use (≥ 4 ED visits) within one year of discharge. Data retrieved from the universal health insurance system was analyzed using Cox Proportional Hazards (PH) model, adopting the Lunn-McNeil approach for competing risk of death. RESULTS: Of 1253 patients, 14.5% became FED users. FED use was associated with chemotherapy one-year pre-admission (adjusted hazard ratio (aHR) 2.60, 95% CI: 1.80-3.70), ≥1 ED visit in the previous year (aHR: 1.80, 95% CI 1.20-2.80), ≥15 pre-admission ambulatory visits (aHR 1.54, 95% CI 1.06-2.34), previous opioid and benzodiazepine use (aHR: 1.40, 95% CI: 1.10-1.90 and aHR: 1.70, 95% CI: 1.10-2.40), Charlson Comorbidity Index ≥ 3 (aHR: 2.0, 95% CI: 1.2-3.4), diabetes (aHR: 1.60, 95% CI: 1.10-2.20), heart disease (aHR: 1.50, 95% CI: 1.10-2.20) and lung cancer (aHR: 1.70, 95% CI: 1.10-2.40). Surgery (cardiac (aHR: 0.33, 95% CI: 0.16-0.66), gastrointestinal (aHR: 0.34, 95% CI: 0.14-0.82) and thoracic (aHR: 0.45, 95% CI: 0.30-0.67) led to a decreased risk of FED use. CONCLUSIONS: Cancer patients with higher co-morbidity, frequent use of the healthcare system, and opioid use were at increased risk of FED use. High-risk patients should be flagged for preventive intervention.

Effects of intraoperative esketamine addition on gastrointestinal function after benign gynaecological laparoscopic surgery: a double-blind, randomized controlled study.

BACKGROUND: Gastrointestinal hypokinesis can occur transiently after benign gynecologic surgery. Opioids cause the side effect of postoperative gastrointestinal hypokinesis, but an opioid-sparing anaesthetic protocol based on esketamine reduces intraoperative opioid consumption. Therefore, this study hypothesised that an opioid-sparing anaesthetic protocol based on esketamine would shorten the gastrointestinal function recovery time after benign gynaecological laparoscopic surgery. METHODS: This was a prospective randomized controlled double-blind study conducted in a single centre. All patients scheduled for elective benign laparoscopic gynaecological surgery at Xing'an Meng People's Hospital, Inner Mongolia Autonomous Region, from November 2021 to April 2022 were consecutively enrolled and randomly divided into the opioid-sparing anaesthesia group (Group OS) and the conventional anaesthesia group (Group C). Postoperative first exhaust time, feeding time and postoperative nausea and/or vomiting (PONV) were analyzed in both groups. RESULTS: A total of 71 patients were enrolled in this study, including 35 in Group OS and 36 in Group C. The general condition, operative time, type of surgery, intraoperative bleeding, intraoperative fluid volume and intraoperative urine volume were not statistically different between the two groups. Compared with Group C, significantly shorter first postoperative flatus time (11 [8, 14] h vs. 14 [11, 18], p = 0.003) and anaesthesia resuscitation time (7 [6, 9] h vs. 9 [7, 11] h, p = 0.013)were observed in the OS group. The incidence of PONV in Group OS was significantly lower compared with Group C (11.4% vs. 41.7%, p = 0.007). CONCLUSION: The esketamine-based opioid-sparing anaesthetic protocol can shorten the postoperative first flatus time after benign laparoscopic surgery in gynaecology, and reduce the incidence of PONV. In addition, the application of esketamine may reduce the postoperative opioid dose requirement of patients. TRIAL REGISTRATION: This study was registered with the China Clinical Trials Registry (registration number: ChiCTR2100052528, 30/10/2021).

Uso de opioides en pacientes con enfermedad crónica avanzada en situación de últimos días / Use of opioids in patients with advanced chronic disease in the last days of life

Objetivo: Conocer el uso de opioides en el paciente con enfermedad crónica avanzada en los últimos días de vida. Métodos: Estudio retrospectivo, multicéntrico, descriptivo y analítico. Se recogieron datos de los servicios de Geriatría del Hospital Universitario La Paz, Medicina Interna del Complejo Hospitalario de Toledo, Unidad de Hospital a Domicilio del Hospital Marina Baixa de la Vila Joiosa y del Hospital Centro de Cuidados Laguna. Se incluyeron en el estudio los pacientes ingresados con enfermedad avanzada no oncológica fallecidos entre el 1 de marzo de 2019 y el 29 de febrero de 2020. Se estudiaron distintas variables: edad, sexo, enfermedad principal, motivo de ingreso, valoración por cuidados paliativos, uso previo de opioides, uso de opioides en situación de últimos días, opioide, dosis, vías de administración e indicación. Resultados: En el estudio se incluyeron 261 pacientes, 143 (55 %) mujeres y 118 (45 %) hombres, con una edad media de 84 años. La enfermedad principal más frecuente fue la demencia, seguido de insuficiencia cardiaca y patología respiratoria. El motivo de ingreso más frecuente fue deterioro debido a la enfermedad de base seguido de infección respiratoria y sepsis. En la situación de últimos días, la mayoría de los pacientes tenían pauta de opioide basal (94 % morfina) y de rescate (98 % morfina). La vía de administración más utilizada fue la subcutánea (98 %) y la indicación más frecuente fue la disnea (42 %). La mediana de dosis equivalente de morfina oral diaria por enfermedad principal y por motivo de ingreso fue de 30 mg/día. Conclusiones: El uso de opioides en las enfermedades crónicas avanzadas en situación de últimos días está ampliamente extendido. La morfina es el opioide más usado, independientemente de la enfermedad. La vía de administración más utilizada es la subcutánea. No encontramos diferencias entre pacientes con diferentes patologías. (AU)

Objective: To determine the use of opioids in patients with advanced chronic disease in the last days of life. Methods: A retrospective, multicenter, descriptive, analytical study. Data were collected from the Geriatrics Department of Hospital La Paz, Internal Medicine Department of Complejo Hospitalario de Toledo, Hospital at Home Unit of Hospital Marina Baixa in0 La Vila Joiosa, and Hospital Centro de Cuidados Laguna. The study included patients with advanced non-oncological disease who died between 1 March 2019 and 29 February 2020. Different variables were studied: age, sex, main disease, reason for admission, palliative care assessment, previous opioid use, opioid use in last days, opioid, dose, routes of administration, and indication. Results: The study included 261 patients, 143 (55 %) women and 118 (45 %) men, with a mean age of 84 years. The most frequent main disease was dementia, followed by heart failure and respiratory pathology. The most frequent reason for admission was deterioration due to the underlying disease followed by respiratory infection and sepsis. In the last-day situation, most patients had a baseline (94 % morphine) and rescue (98 % morphine) opioid regimen. The most common route of administration was subcutaneous (98 %) and the most common indication was dyspnea (42 %). The median daily oral morphine equivalent dose per main disease and reason for admission was 30 mg/day. Conclusions: The use of opioids in advanced chronic illness in the last days situation is widespread. Morphine is the most commonly used opioid regardless of disease. The most used route of administration is subcutaneous. We found no differences between patients with different pathologies. (AU)

Racial Inequality in Receipt of Medications for Opioid Use Disorder.

BACKGROUND: Since 2010, Black persons in the United States have had a greater increase in opioid overdose-related mortality than other groups, but national-level evidence characterizing racial and ethnic disparities in the use of medications for opioid use disorder (OUD) is limited. METHODS: We used Medicare claims data from the 2016-2019 period for a random 40% sample of fee-for-service beneficiaries who were Black, Hispanic, or White; were eligible for Medicare owing to disability; and had an index event related to OUD (nonfatal overdose treated in an emergency department or inpatient setting, hospitalization with injection drug use-related infection, or inpatient or residential rehabilitation or detoxification care). We measured the receipt of medications to treat OUD (buprenorphine, naltrexone, and naloxone), the receipt of high-risk medications (opioid analgesics and benzodiazepines), and health care utilization, all in the 180 days after the index event. We estimated differences in outcomes according to race and ethnic group with adjustment for beneficiary age, sex, index event, count of chronic coexisting conditions, and state of residence. RESULTS: We identified 25,904 OUD-related index events among 23,370 beneficiaries, with 3937 events (15.2%) occurring among Black patients, 2105 (8.1%) among Hispanic patients, and 19,862 (76.7%) among White patients. In the 180 days after the index event, patients received buprenorphine after 12.7% of events among Black patients, after 18.7% of those among Hispanic patients, and after 23.3% of those among White patients; patients received naloxone after 14.4%, 20.7%, and 22.9%, respectively; and patients received benzodiazepines after 23.4%, 29.6%, and 37.1%, respectively. Racial differences in the receipt of medications to treat OUD did not change appreciably from 2016 to 2019 (buprenorphine receipt: after 9.1% of index events among Black patients vs. 21.6% of those among White patients in 2016, and after 14.1% vs. 25.5% in 2019). In all study groups, patients had multiple ambulatory visits in the 180 days after the index event (mean number of visits, 6.6 after events among Black patients, 6.7 after events among Hispanic patients, and 7.6 after events among White patients). CONCLUSIONS: Racial and ethnic differences in the receipt of medications to treat OUD after an index event related to this disorder among patients with disability were substantial and did not change over time. The high incidence of ambulatory visits in all groups showed that disparities persisted despite frequent health care contact. (Funded by the National Institute on Drug Abuse and the National Institute on Aging.).

Comparison of intravenous paracetamol (acetaminophen) to intravenously or intramuscularly administered non-steroidal anti-inflammatory drugs (NSAIDs) or opioids for patients presenting with moderate to severe acute pain conditions to the ED: systematic review and meta-analysis.

OBJECTIVE: Paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opiates/opioids, administered parenterally via intravenous or intramuscular route, are widely used to provide analgesia for patients with moderate to severe pain. This systematic review and meta-analysis evaluated the level of analgesia provided by intravenous paracetamol (IVP) alone compared with NSAIDs (intravenous or intramuscular), or opioids (intravenous) alone in adults attending the ED with acute pain. METHODS: Two authors independently searched PubMed (MEDLINE), Web of Science, Embase (OVID), Cochrane Library, SCOPUS and Google Scholar (3 March 2021-20 May 2022) for randomised trials without any language or date restriction. Clinical trials were evaluated using the Risk of Bias V.2 tool. The primary outcome was mean difference (MD) for pain reduction at 30 min (T30) post analgesia delivery. The secondary outcomes were MD in pain reduction at 60, 90 and 120 min; the need for rescue analgesia; and the occurrence of adverse events (AEs). RESULTS: Twenty-seven trials (5427 patients) were included in the systematic review and 25 trials (5006 patients) in the meta-analysis. There was no significant difference in pain reduction at T30 between the IVP group and opioids (MD -0.13, 95% CI -1.49 to 1.22) or IVP and NSAIDs (MD -0.27, 95% CI -1.0 to 1.54. There was also no difference at 60 min, IVP group versus opioid group (MD -0.09, 95% CI -2.69 to 2.52) or IVP versus NSAIDs (MD 0.51, 95% CI 0.11 to 0.91). The quality of the evidence using Grading of Recommendations, Assessments, Development and Evaluations methodology was low for MD in pain scores.The need for rescue analgesia at T30 was significantly higher in the IVP group compared with the NSAID group (risk ratio (RR): 1.50, 95% CI 1.23 to 1.83), with no difference found between the IVP group and the opioid group (RR: 1.07, 95% CI 0.67 to 1.70). AEs were 50% lower in the IVP group compared with the opioid group (RR: 0.50, 95% CI 0.40 to 0.62), whereas no difference was observed in the IVP group compared with the NSAID group (RR: 1.30, 95% CI 0.78 to 2.15). CONCLUSION: In patients presenting to the ED with a diverse range of pain conditions, IVP provides similar levels of pain relief compared with opiates/opioids or NSAIDs at T30 post administration. Patients treated with NSAIDs had lower risk of rescue analgesia, and opioids cause more AEs, suggesting NSAIDs as the first-choice analgesia and IVP as a suitable alternative. PROSPERO REGISTRATION NUMBER: CRD42021240099.

Efficacy of reconstituted intravenous fentanyl to sublingual solution versus oral morphine syrup for breakthrough pain among patients with chronic gynecologic cancer pain: A randomized, double-blind, placebo-controlled trial.

Rapid-acting fentanyl formulations are superior to oral morphine (OM) syrup in controlling breakthrough pain among patients with cancer, but they are expensive and unavailable in many countries. OBJECTIVE: To evaluate the efficacy of reconstituted intravenous fentanyl to sublingual solution (IFS) in relieving breakthrough pain as compared with OM. METHODS: In this randomized, double-blind, double-dummy, placebo-controlled trial, patients with gynecologic cancer aged ≥18 years experiencing chronic cancer pain with breakthrough pain were enrolled. Patients were randomly allocated (1:1) to receive either 50 µg IFS or 5 mg OM. Pain intensity level was assessed at 5, 15, 30, 45, 60, and 120 min after treatment. The primary outcome was the reduction in pain intensity at 15 min in the intention-to-treat population (ClinicalTrials.gov, NCT05037539). RESULTS: Between June 15, 2021 and December 30, 2021, 40 participants were equally and randomly assigned to receive IFS or OM. The primary outcome was significantly higher in the IFS group (4.25 vs. 1.05, p < 0.0001). The secondary outcomes also showed higher reduction in pain intensity at 5 min in the IFS group. Subsequent breakthrough pain did not differ between the two groups. However, the reduction in pain was lower in the IFS group at 45, 60, and 120 min, where pain was classified as mild. No severe adverse effects were observed in both groups. Burning sensation without noticeable lesion was found in 20% of the IFS group. CONCLUSION: IFS can reduce early breakthrough pain. IFS may be considered for breakthrough pain when rapid-acting fentanyl formulations are unavailable.