Intrathecal Morphine for Cardiac Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Cardiac surgeries often result in significant postoperative pain, leading to considerable use of opioids for pain management. However, excessive opioid use can lead to undesirable side effects and chronic opioid use. This systematic review and meta-analysis aimed to evaluate whether preoperative intrathecal morphine could reduce postoperative opioid consumption in patients undergoing cardiac surgery requiring sternotomy. We conducted a systematic search of Cochrane, EMBASE, and MEDLINE databases from inception to May 2022 for randomized controlled trials that evaluated the use of intrathecal morphine in patients undergoing cardiac surgery. Studies that evaluated intrathecal administration of other opioids or combinations of medications were excluded. The primary outcome was postoperative morphine consumption at 24 h. Secondary outcomes included time to extubation and hospital length of stay. The final analysis included ten randomized controlled trials, with a total of 402 patients. The results showed that postoperative morphine consumption at 24 h was significantly lower in the intervention group (standardized mean difference -1.43 [-2.12, -0.74], 95% CI, P < 0.0001). There were no significant differences in time to extubation and hospital length of stay. Our meta-analysis concluded that preoperative intrathecal morphine is associated with lower postoperative morphine consumption at 24 h following cardiac surgeries, without prolonging the time to extubation. The use of preoperative intrathecal morphine can be considered part of a multimodal analgesic and opioid-sparing strategy in patients undergoing cardiac surgery.

Effectiveness and safety of prehospital analgesia with nalbuphine and paracetamol versus morphine by paramedics - an observational study.

BACKGROUND: Despite the development of various analgesic concepts, prehospital oligoanalgesia remains very common. The present work examines prehospital analgesia by paramedics using morphine vs. nalbuphine + paracetamol. METHODS: Patients with out-of-hospital-analgesia performed by paramedics from the emergency medical services of the districts of Fulda (morphine) and Gütersloh (nalbuphine + paracetamol) were evaluated with regards to pain intensity at the beginning and the end of prehospital treatment using the Numeric-Rating-Scale for pain (NRS), sex, age, and complications. The primary endpoint was achievement of adequate analgesia, defined as NRS < 4 at hospital handover, depending on the analgesics administered (nalbuphine + paracetamol vs. morphine). Pain intensity before and after receiving analgesia using the NRS, sex, age and complications were also monitored. RESULTS: A total of 1,808 patients who received out-of-hospital-analgesia were evaluated (nalbuphine + paracetamol: 1,635 (90.4%), NRS-initial: 8.0 ± 1.4, NRS-at-handover: 3.7 ± 2.0; morphine: 173(9.6%), NRS-initial: 8.5 ± 1.1, NRS-at-handover: 5.1 ± 2.0). Factors influencing the difference in NRS were: initial pain intensity on the NRS (regression coefficient (RK): 0.7276, 95%CI: 0.6602-0.7950, p < 0.001), therapy with morphine vs. nalbuphine + paracetamol (RK: -1.2594, 95%CI: -1.5770 - -0.9418, p < 0.001) and traumatic vs. non-traumatic causes of pain (RK: -0.2952, 95%CI: -0.4879 - -0.1024, p = 0.002). Therapy with morphine (n = 34 (19.6%)) compared to nalbuphine + paracetamol (n = 796 (48.7%)) (odds ratio (OR): 0.274, 95%CI: 0.185-0.405, p < 0.001) and the initial NRS score (OR:0.827, 95%CI: 0.771-0.887, p < 0.001) reduced the odds of having an NRS < 4 at hospital handover. Complications occurred with morphine in n = 10 (5.8%) and with nalbuphine + paracetamol in n = 35 (2.1%) cases. Risk factors for complications were analgesia with morphine (OR: 2.690, 95%CI: 1.287-5.621, p = 0.008), female sex (OR: 2.024, 95%CI: 1.040-3.937, p = 0.0379), as well as age (OR: 1.018, 95%CI: 1.003-1.034, p = 0.02). CONCLUSIONS: Compared to morphine, prehospital analgesia with nalbuphine + paracetamol yields favourable effects in terms of analgesic effectiveness and a lower rate of complications and should therefore be considered in future recommendations for prehospital analgesia.

Dexmedetomidine for analgesia and sedation in newborn infants receiving mechanical ventilation.

BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group. OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety. AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.

Opioid Coprescription Through Risk Mitigation Guidance and Opioid Agonist Treatment Receipt.

Importance: At the onset of the COVID-19 pandemic, the government of British Columbia, Canada, released clinical guidance to support physicians and nurse practitioners in prescribing pharmaceutical alternatives to the toxic drug supply. These alternatives included opioids and other medications under the risk mitigation guidance (RMG), a limited form of prescribed safer supply, designed to reduce the risk of SARS-CoV-2 infection and harms associated with illicit drug use. Many clinicians chose to coprescribe opioid medications under RMG alongside opioid agonist treatment (OAT). Objective: To examine whether prescription of hydromorphone tablets or sustained-release oral morphine (opioid RMG) and OAT coprescription compared with OAT alone is associated with subsequent OAT receipt. Design, Setting, and Participants: This population-based, retrospective cohort study was conducted from March 27, 2020, to August 31, 2021, included individuals from 10 linked health administrative databases from British Columbia, Canada. Individuals who were receiving OAT at opioid RMG initiation and individuals who were receiving OAT and eligible but unexposed to opioid RMG were propensity score matched at opioid RMG initiation on sociodemographic and clinical variables. Data were analyzed between January 2023 and February 2024. Exposure: Opioid RMG receipt (≥4 days, 1-3 days, or 0 days of opioid RMG dispensed) in a given week. Main Outcome and Measures: The main outcome was OAT receipt, defined as at least 1 dispensed dose of OAT in the subsequent week. A marginal structural modeling approach was used to control for potential time-varying confounding. Results: A total of 4636 individuals (2955 [64%] male; median age, 38 [31-47] years after matching) were receiving OAT at the time of first opioid RMG dispensation (2281 receiving ongoing OAT and 2352 initiating RMG and OAT concurrently). Opioid RMG receipt of 1 to 3 days in a given week increased the probability of OAT receipt by 27% in the subsequent week (adjusted risk ratio, 1.27; 95% CI, 1.25-1.30), whereas receipt of opioid RMG for 4 days or more resulted in a 46% increase in the probability of OAT receipt in the subsequent week (adjusted risk ratio, 1.46; 95% CI, 1.43-1.49) compared with those not receiving opioid RMG. The biological gradient was robust to different exposure classifications, and the association was stronger among those initiating opioid RMG and OAT concurrently. Conclusions and Relevance: This cohort study, which acknowledged the intermittent use of both medications, demonstrated that individuals who were coprescribed opioid RMG had higher adjusted probability of continued OAT receipt or reengagement compared with those not receiving opioid RMG.

Commonly used antiemetics for prophylaxis of postoperative nausea and vomiting after Caesarean delivery with neuraxial morphine: a network meta-analysis.

BACKGROUND: Dopamine antagonists, 5-HT3 antagonists, and dexamethasone are frequently used in obstetrics to prevent postoperative nausea and vomiting (PONV). However, the superiority of any drug class is yet to be established. This network meta-analysis aimed to compare the efficacy of these antiemetics for PONV prophylaxis in women receiving neuraxial morphine for Caesarean delivery. METHODS: We searched PubMed, Embase, CENTRAL, Web of Science, and Wanfang Data for eligible randomised controlled trials. Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) within 24 h after surgery. We used a Bayesian random-effects model and calculated odds ratios with 95% credible intervals for dichotomous data. We performed sensitivity and subgroup analyses for primary outcomes. RESULTS: A total of 33 studies with 4238 women were included. In the primary analyses of all women, 5-HT3 antagonists, dopamine antagonists, dexamethasone, and 5-HT3 antagonists plus dexamethasone significantly reduced PON and POV compared with placebo, and 5-HT3 antagonists plus dexamethasone were more effective than monotherapy. In the subgroup analyses, similar results were seen in women receiving epidural morphine or intrathecal morphine alone but not in women receiving intrathecal morphine with fentanyl or sufentanil. However, most included studies had some concerns or a high risk of bias, and the overall certainty of the evidence was low or very low. CONCLUSIONS: Combined 5-HT3 antagonists plus dexamethasone are more effective than monotherapy in preventing PONV associated with neuraxial morphine after Caesarean delivery. Future studies are needed to determine the role of prophylactic antiemetics in women receiving intrathecal morphine and lipophilic opioids. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023454602.

Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial.

BACKGROUND: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass. METHODS: Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%. RESULTS: In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion - 3.1% (95% CI - 16.6-10.3%). CONCLUSIONS: In children aged 0-3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.

Low-dose ketamine safely reduces acute pain in the ED with a more rapid and shorter effect than morphine.

SOURCE CITATION: Guo J, Zhao F, Bian J, et al. Low-dose ketamine versus morphine in the treatment of acute pain in the emergency department: a meta-analysis of 15 randomized controlled trials. Am J Emerg Med. 2024;76:140-149. 38071883.

Severe pain management in the emergency department: patient pathway as a new factor associated with IV morphine prescription.

Background: Across the world, 25-29% of the population suffer from pain. Pain is the most frequent reason for an emergency department (ED) visit. This symptom is involved in approximately 70% of all ED visits. The effective management of acute pain with adequate analgesia remains a challenge, especially for severe pain. Intravenous (IV) morphine protocols are currently indicated. These protocols are based on patient-reported scores, most often after an immediate evaluation of pain intensity at triage. However, they are not systematically prescribed. This aspect could be explained by the fact that physicians individualize opioid pain management for each patient and each care pathway to determine the best benefit-risk balance. Few data are available regarding bedside organizational factors involved in this phenomenon. Objective: This study aimed to analyze the organizational factors associated with no IV morphine prescription in a standardized context of opioid management in a tertiary-care ED. Methods: A 3-month prospective study with a case-control design was conducted in a French university hospital ED. This study focused on factors associated with protocol avoidance despite a visual analog scale (VAS) ≥60 or a numeric rating scale (NRS) ≥6 at triage. Pain components, physician characteristics, patient epidemiologic characteristics, and care pathways were considered. Qualitative variables (percentages) were compared using Fisher's exact test or the chi-squared tests. Student's t-test was used to compare continuous variables. The results were expressed as means with their standard deviation (SD). Factors associated with morphine avoidance were identified by logistic regression. Results: A total of 204 patients were included in this study. A total of 46 cases (IV morphine) and 158 controls (IV morphine avoidance) were compared (3:1 ratio). Pain patterns and patient's epidemiologic characteristics were not associated with an IV morphine prescription. Regarding NRS intervals, the results suggest a practice disconnected from the patient's initial self-report. IV morphine avoidance was significantly associated with care pathways. A significant difference between the IV morphine group and the IV morphine avoidance group was observed for "self-referral" [adjusted odds ratio (aOR): 5.11, 95% CIs: 2.32-12.18, p < 0.0001] and patients' trajectories (Fisher's exact test; p < 0.0001), suggesting IV morphine avoidance in ambulatory pathways. In addition, "junior physician grade" was associated with IV morphine avoidance (aOR: 2.35, 95% CIs: 1.09-5.25, p = 0.03), but physician gender was not. Conclusion: This bedside case-control study highlights that IV morphine avoidance in the ED could be associated with ambulatory pathways. It confirms the decreased choice of "NRS-only" IV morphine protocols for all patients, including non-trauma patterns. Modern pain education should propose new tools for pain evaluation that integrate the heterogeneity of ED pathways.

Comparison of analgesic efficacy of tramadol, morphine and methadone in cats undergoing ovariohysterectomy.

OBJECTIVES: The aim of this study was to compare the analgesic efficacy and the effect on physiological variables and behavior of the use of tramadol, methadone and morphine as preoperative analgesia in healthy cats undergoing elective ovariohysterectomy. METHODS: Cats undergoing ovariohysterectomy were randomly assigned to receive one of the following premedication treatments intramuscularly: methadone (0.2 mg/kg; n = 10); morphine (0.2 mg/kg; n = 10); or tramadol (3 mg/kg; n = 10). Induction of anesthesia was done with propofol, and maintenance of anesthesia was done with isoflurane. Intraoperative heart rate, arterial blood pressure, respiratory rate, end-tidal isoflurane concentration and frequency of rescue analgesia (fentanyl 2.5 µg/kg) were compared between groups. Postoperative analgesia was assessed using the UNESP-Botucatu Multidimensional Composite Pain Scale, and perioperative serum glucose, cortisol concentrations and postoperative rescue analgesia were evaluated. RESULTS: Intraoperative rescue analgesia was required in 76.5% of cats at some time during surgery, and 27% of cats required postoperative rescue analgesia up to 6 h after extubation. There were no significant differences between groups with respect to intraoperative and postoperative rescue analgesia, pain scale scores and end-tidal isoflurane concentrations. In the immediate postoperative period, after extubation, most of the patients presented with hypothermia; however, 1-6 h postoperatively, hyperthermia was observed in most of the patients, and was most common in the tramadol group. CONCLUSIONS AND CLINICAL RELEVANCE: Under the conditions of this study, methadone, morphine and tramadol produced satisfactory postoperative analgesia in most of the cats undergoing ovariohysterectomy, and the effects lasted up to 6 h postoperatively. Intraoperative analgesia was not sufficient in most cases. Significant cardiovascular or respiratory effects contraindicating the use of these drugs were not found. Postanesthetic hyperthermia occurred with all opioids studied and was more frequent in the tramadol group.

Robot-assisted laparoscopic nephrectomy: early outcome measures with the implementation of multimodal analgesia and intrathecal morphine via the acute pain service.

PURPOSE: The objective of this study was to perform a retrospective cohort analysis, in which we measured the association of an acute pain service (APS)-driven multimodal analgesia protocol that included preoperative intrathecal morphine (ITM) compared to historic controls (i.e., surgeon-driven analgesia protocol without ITM) with postoperative opioid use. METHODS: This was a retrospective cohort study in which the primary objective was to determine whether there was a decrease in median 24-h opioid consumption (intravenous morphine equivalents [MEQ]) among robotic nephrectomy patients whose pain was managed by the surgical team prior to the APS, versus pain managed by APS. Secondary outcomes included opioid consumption during the 24-48 h and 48-72 h period and hospital length of stay. To create matched cohorts, we performed 1:1 (APS:non-APS) propensity score matching. Due to the cohorts occurring at the different time periods, we performed a segmented regression analysis of an interrupted time series. RESULTS: There were 76 patients in the propensity-matched cohorts, in which 38 (50.0%) were in the APS cohort. The median difference in 24-h opioid consumption in the pre-APS versus APS cohort was 23.0 mg [95% CI 15.0, 31.0] (p < 0.0001), in favor of APS. There were no differences in the secondary outcomes. On segmented regression, there was a statistically significant drop in 24-h opioid consumption in the APS cohort versus pre-APS cohort (p = 0.005). CONCLUSIONS: The implementation of an APS-driven multimodal analgesia protocol with ITM demonstrated a beneficial association with postoperative 24-h opioid consumption following robot-assisted nephrectomy.

Cocktail of Ropivacaine, Morphine, and Diprospan Reduces Pain and Prolongs Analgesic Effects after Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

Background: Local infiltration analgesia (LIA) provides postoperative analgesia for total knee arthroplasty (TKA). The purpose of this study was to evaluate the analgesic effect of a cocktail of ropivacaine, morphine, and Diprospan for TKA. Methods: A total of 100 patients from September 2018 to February 2019 were randomized into 2 groups. Group A (control group, 50 patients) received LIA of ropivacaine alone (80 ml, 0.25% ropivacaine). Group B (LIA group, 50 patients) received an LIA cocktail of ropivacaine, morphine, and Diprospan (80 ml, 0.25% ropivacaine, 0.125 mg/ml morphine, and 62.5 µg/ml compound betamethasone). The primary outcomes were the levels of inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), pain visual analog scale (VAS) scores, opioid consumption, range of motion (ROM), functional tests, and sleeping quality. The secondary outcomes were adverse events, satisfaction rates, HSS scores, and SF-12 scores. The longest follow-up was 2 years. Results: The two groups showed no differences in terms of characteristics (P > 0.05). Group B had lower resting VAS pain scores (1.54 ± 0.60, 95% CI = 1.37 to 1.70 vs. 2.00 ± 0.63, 95% CI = 2.05 to 2.34) and active VAS pain scores (2.64 ± 0.62, 95% CI = 2.46 to 2.81 vs. 3.16 ± 0.75, 95% CI = 2.95 to 3.36) within 48 h postoperatively than Group A (P < 0.001), while none of the pain differences exceeded the minimal clinically important difference (MCID). Group B had significantly lower CRP levels (59.49 ± 13.01, 95% CI = 55.88 to 63.09 vs. 65.95 ± 14.41, 95% CI = 61.95 to 69.94) and IL-6 levels (44.11 ± 13.67, 95% CI = 40.32 to 47.89 vs. 60.72 ± 15.49, 95% CI = 56.42 to 65.01), lower opioid consumption (7.60 ± 11.10, 95% CI = 4.52 to 10.67 vs. 13.80 ± 14.68, 95% CI = 9.73 to 17.86), better ROM (110.20 ± 10.46, 95% CI = 107.30 to 113.09 vs. 105.30 ± 10.02, 95% CI = 102.52 to 108.07), better sleep quality (3.40 ± 1.03, 95% CI = 3.11 to 3.68 vs. 4.20 ± 1.06, 95% CI = 3.90 to 4.49), and higher satisfaction rates than Group A within 48 h postoperatively (P < 0.05). Adverse events, HSS scores, and SF-12 scores were not significantly different within 2 years postoperatively. Conclusions: A cocktail of ropivacaine, morphine, and Diprospan prolongs the analgesic effect up to 48 h postoperatively. Although the small statistical benefit may not result in MCID, the LIA cocktail still reduces opioid consumption, results in better sleeping quality and faster rehabilitation, and does not increase adverse events. Therefore, cocktails of ropivacaine, morphine, and Diprospan have good application value for pain control in TKA. This trial is registered with ChiCTR1800018372.

Impact of Preoperative Aripiprazole on Postoperative Analgesia in Laparoscopic Hysterectomy: A Randomized Double-blind Placebo-controlled Trial.

OBJECTIVES: Aripiprazole is a second-generation atypical antipsychotic with worldwide clinical approval. Nevertheless, its perioperative antinociceptive application has not been studied. As a result, the purpose of this study was to investigate the analgesic effects of perioperative aripiprazole on reducing postoperative pain, as well as the possible adverse effects. PATIENTS AND METHODS: This randomized controlled study enrolled 80 female patients scheduled for laparoscopic hysterectomy who were assigned randomly into 2 equal groups in 1:1; aripiprazole group (n = 40), patients received an aripiprazole 30 mg tablet orally 3 hours before surgery and placebo group (n = 40), patients received a placebo tablet 3 hours before surgery. The 24-hour morphine consumption postoperatively was the primary outcome, and the time to the first analgesic request, sedation scores, and the incidence of perioperative adverse events were the secondary outcomes. RESULTS: The mean 24-hour morphine consumption was significantly lower with aripiprazole (2.5 ± 0.5 mg) than with placebo (23.7 ± 1.6 mg; mean ± SE -21.2 ± 0.3, 95% CI: -21.7 to -20.6, P < 0.001). In addition, the mean time to the first analgesic request was significantly longer with aripiprazole (212.2 ± 14.7 min) than with placebo (27.0 ± 2.0 min; mean ± SE 185.2 ± 2.3, 95% CI: 180.5 to 189.8, P < 0.001). Furthermore, the aripiprazole group reported higher sedation scores ( P < 0.001). Bradycardia and hypotension were reported more frequently among patients in the aripiprazole group ( P < 0.05). CONCLUSION: Aripiprazole was effective in reducing pain after laparoscopic hysterectomy. Although self-limited, side effects should be taken into consideration when using the medication perioperatively.

Cryoablation Reduces Opioid Consumption and Length of Stay After Pulmonary Metastasectomy.

INTRODUCTION: Intraoperative cryoablation of intercostal thoracic nerves is gaining popularity as a technique that decreases postoperative pain in thoracic surgery. Our study evaluates the efficacy and safety of cryoablation in pain management of pediatric cancer patients undergoing thoracotomy. METHODS: We reviewed cancer patients undergoing thoracotomies for pulmonary metastasis resection at our children's hospital from 2017 to 2023. Patients who received cryoablation were compared to those who did not. Our primary outcomes were self-reported postoperative pain scores (from 0 to 10) and opioid consumption, measured as oral morphine equivalent per kilogram. RESULTS: Thirty eight procedures were performed in 17 patients, of which 11 (64.7%) were males. Cryoablation was used in 14 (32.4%) procedures, while it was not in 24 (67.6%). Median age (17 y in both groups, P = 0.84) and length of surgery (300 cryoablation versus 282 no cryoablation, P = 0.65) were similar between the groups. Patients treated with cryoablation had a shorter hospital stay compared to those who did not (3.0 versus 4.5 d, respectively, P = 0.04) and received a lower total dose of opioids (2.2 oral morphine equivalent per kilogram versus 14.4, P = 0.004). No significant difference was noted in daily pain scores between the two groups (3.8 cryoablation versus 3.9 no cryoablation, P = 0.93). There was no difference in rates of readmissions between the cryoablation and no-cryoablation groups (14.3% versus 8.3%, P = 0.55). CONCLUSIONS: Our study suggests that cryoablation of the thoracic nerves during a thoracotomy is associated with reduced opiate consumption and shorter hospital stay. Cryoablation appears to be a promising technique for pain management in this patient population.

Implementing physics-based digital patient twins to tailor the switch of oral morphine to transdermal fentanyl patches based on patient physiology.

Fentanyl transdermal patches are widely implemented for cancer-induced pain treatment due to the high potency of fentanyl and gradual drug release. However, transdermal fentanyl up-titration for opioid-naïve patients is difficult, which is why opioid treatment is often started with oral/iv morphine. Based on the daily dose of morphine, the initial dose of the fentanyl patch is decided upon. After reaching a stable level of pain, the switch is made from oral/iv morphine to transdermal fentanyl. There are standard calculation tools for transferring from oral/iv morphine to transdermal fentanyl, which is the same for all patients. By considering the variations in the physiology of the patients, a unique switching strategy cannot meet the needs of different patients. This study explores the outcome in terms of pain relief and minute ventilation during opioid therapy. For this, we used physics-based simulations on a virtually-generated population of patients, and we applied the same therapy to all patients. We could show that patients' physiology, such as gender, age, and weight, greatly impact the outcome of the therapy; as such, the correlation coefficient between pain intensity and age is 0.89, and the correlation coefficient between patient's weight and maximum plasma concentration of morphine and fentanyl is -0.98 and -0.97. Additionally, a different combination of the duration of overlap between morphine and fentanyl therapy with different doses of fentanyl was considered for the virtual patients to find the best opioid-switching strategy for each patient. We explored the impact of combining physiological features to determine the best-suited strategy for virtual patients. Our findings suggest that tailoring morphine and fentanyl therapy only based on a limited number of features is insufficient, and increasing the number of impactful physiological features positively influences the outcome of the therapy.

Treatment of patients with chronic malignant pain with intrathecal morphine.

Chronic malignant pain is a common and feared condition. Especially, since many patients do not achieve proper pain relief from conventional peroral medication regimes and possible unacceptable side effects of high dosing. As argued in this review, in these patients, continuous intrathecal infusion of pain medicine by a programmable subcutaneously placed pump enables good pain relief, less systemic side effects, and better life quality. Intrathecal pain treatment should therefore be considered in patients with a proper performance score and suitable estimated life expectancy.

Safety and effectiveness of opioid-free anaesthesia in thoracoscopic surgery: a preliminary retrospective cohort study.

BACKGROUND: This study aimed to observe the effect of opioid-free anaesthesia (OFA) on intraoperative haemodynamic,postoperative analgesia and postoperative nausea and vomiting (PONV) in thoracoscopic surgery in order to provide more evidence for evaluating the safety and effectiveness of OFA technology. METHODS: This was a single-centre retrospective observational study.Adult patients who underwent thoracoscopic surgery with the preoperative thoracic paravertebral block between January 2017 and June 2020 were included.A cohort of 101 thoracoscopic surgery patients who received the OFA technique were matched with 101 thoracoscopic surgery patients who received standard opioid-containing anaesthesia(SOA). Heart rate (HR) and mean arterial blood pressure (MAP) were measured before anaesthesia induction, immediately after endotracheal intubation, at the beginning of surgery, and 10, 20, and 30 min after surgery began.The total amount of intraoperative infusion, frequency of vasoactive drugs use, morphine ingested via the patient-controlled intravenous analgesia (PCIA) 24 h post-surgery,visual analogue scale (VAS) scores at rest and activity on the first day post-surgery, and frequency of nausea and vomiting within 24 h post-surgery were analysed. RESULTS: There was no significant difference in intraoperative HR between the two groups (F = 0.889, P = 0.347); however, there was significant difference in intraoperative MAP (F = 16.709, P < 0.001), which was lower in SOA patients than in OFA patients. The frequency of vasoactive drug use and amount of infusion was less in OFA patients (P = 0.001). The consumption of morphine used by the PCIA 24 h post-surgery was significantly lower in OFA patients (OFA, 1.8 [0, 4.8] mg vs. SOA, 3.6 [0.6, 23] mg, P < 0.001). There was no significant difference in VAS scores at rest (P = 0.745) or during activity (P = 0.792) on the first day post-surgery. There was also no statistically significant difference in nausea and vomiting within 24 h post-surgery (P = 0.651). CONCLUSIONS: This case-control study demonstrated that compared with SOA, OFA can effectively maintain the stability of intraoperative MAP, reduce the incidence of hypotension. Although OFA reduced morphine consumption via the PCIA pump 24 h post-surgery, postoperative pain scores and nausea and vomiting within 24 h post-surgery were similar between the groups.But this study was only a preliminary study and needed to confirm in a larger, more robust trial.

Efficacy of intraoperative systemic lidocaine on quality of recovery after laparoscopic colorectal surgery: a randomized controlled trial.

INTRODUCTION: Many clinical trials have demonstrated the benefits of intraoperative systemic lidocaine administration in major abdominal surgeries. We tested the hypothesis that systemic lidocaine is associated with an enhanced early quality of recovery in patients following laparoscopic colorectal resection. PATIENTS AND METHODS: We randomly allocated 126 patients scheduled for laparoscopic colorectal surgery in a 1:1 ratio to receive either lidocaine (1.5 mg kg-1 bolus over 10 min, followed by continuous infusion at 2 mg kg-1 h-1 until the end of surgery) or identical volumes and rates of saline. The primary outcome was the Quality of Recovery-15 score assessed 24 h after surgery. Secondary outcomes were areas under the pain numeric rating scale curve over time, 48-h morphine consumption, and adverse events. RESULTS: Compared with saline, systemic lidocaine improved the Quality of Recovery-15 score 24 h postoperatively, with a median difference of 4 (95% confidence interval: 1-6; p = 0.015). Similarly, the area under the pain numeric rating scale curve over 48 h at rest and on movement was reduced in the lidocaine group (p = 0.004 and p < 0.001, respectively). However, these differences were not clinically meaningful. Lidocaine infusion reduced the intraoperative remifentanil requirements but not postoperative 48-h morphine consumption (p < 0.001 and p = 0.34, respectively). Additionally, patients receiving lidocaine had a quicker and earlier return of bowel function, as indicated by a shorter time to first flatus (log-rank p < 0.001), yet ambulation time was similar between groups (log-rank test, p = 0.11). CONCLUSIONS: In patients undergoing laparoscopic colorectal surgery, intraoperative systemic lidocaine resulted in statistically but not clinically significant improvements in quality of recovery (see Graphical Abstract).Trial registration: Chinese Clinical Trial Registry; ChiCTR1900027635.

Systemic lidocaine failed to clinically improve the overall quality of recovery following laparoscopic colorectal resection.Systemic lidocaine reduced intraoperative remifentanil and time to first flatus but not postoperative 48-h morphine consumption.No differences emerged in patient-reported outcomes like opioid side effects, mobility, or satisfaction between groups postoperatively.

Associations of dexamethasone's effect on morphine consumption after total knee arthroplasty-Subgroup analyses.

The DEXamethasone twice for pain treatment after Total Knee Arthroplasty (DEX-2-TKA) trial showed that adding one and two doses of 24 mg intravenous dexamethasone to paracetamol, ibuprofen and local infiltration analgesia, reduced morphine consumption (primary outcome) within 48 h after TKA. We aimed to explore the differences in the effect of dexamethasone on morphine consumption in different subgroups. Quantile regression adjusted for site was used to test for significant interaction between the predefined dichotomised subgroups and treatment group. The subgroups were defined based on baseline data: sex (male/female), age (≤65 years/>65 years), American Society of Anaesthesiologists (ASA)-score (ASA I + II/III), visual analogue score of preoperative pain at rest (≤30 mm/>30 mm), pain during mobilisation (≤30 mm/>30 mm), type of anaesthesia (spinal anaesthesia/general anaesthesia and spinal converted to general anaesthesia), and prior daily use of analgesics (either paracetamol and/or NSAID/neither). These analyses were supplemented with post hoc multivariate linear regression analyses. Test of interaction comparing sex in the pairwise comparison between DX2 (dexamethasone [24 mg] + dexamethasone [24 mg]) versus placebo (p = .02), showed a larger effect of dexamethasone on morphine consumption in male patients compared to females. Test of interaction comparing age in the pairwise comparison between DX1 (dexamethasone [24 mg] + placebo) versus placebo (p = .04), showed a larger effect of dexamethasone on morphine consumption in younger patients (≤65 years) compared to older. All remaining subgroup analyses showed no evidence of a difference. The supplemental multivariate analyses did not support any significant interaction for sex (p = .256) or age (p = .730) but supported a significant interaction with the type of anaesthesia (p < .001). Our results from the quantile regression analyses indicate that the male sex and younger age (≤65 years) may be associated with a larger analgesic effect of dexamethasone than the effects in other types of patients. However, this is not supported by post-hoc multivariate linear regression analyses. The two types of analyses both supported a possible interaction with the type of anaesthesia.

Ketamine Compared With Morphine for Out-of-Hospital Analgesia for Patients With Traumatic Pain: A Randomized Clinical Trial.

Importance: Pain is a common out-of-hospital symptom among patients, and opioids are often prescribed. Research suggests that overprescribing for acute traumatic pain is still prevalent, even when limits restricting opioid prescriptions have been implemented. Ketamine hydrochloride is an alternative to opioids in adults with out-of-hospital traumatic pain. Objective: To assess the noninferiority of intravenous ketamine compared with intravenous morphine sulfate to provide pain relief in adults with out-of-hospital traumatic pain. Design, Setting, and Participants: The Intravenous Subdissociative-Dose Ketamine Versus Morphine for Prehospital Analgesia (KETAMORPH) study was a multicenter, single-blind, noninferiority randomized clinical trial comparing ketamine hydrochloride (20 mg, followed by 10 mg every 5 minutes) with morphine sulfate (2 or 3 mg every 5 minutes) in adult patients with out-of-hospital trauma and a verbal pain score equal to or greater than 5. Enrollment occurred from November 23, 2017, to November 26, 2022, in 11 French out-of-hospital emergency medical units. Interventions: Patients were randomly assigned to ketamine (n = 128) or morphine (n = 123). Main Outcomes and Measures: The primary outcome was the between-group difference in mean change in verbal rating scale pain scores measured from the time before administration of the study drug to 30 minutes later. A noninferiority margin of 1.3 was chosen. Results: A total of 251 patients were randomized (median age, 51 [IQR, 34-69] years; 111 women [44.9%] and 140 men [55.1%] among the 247 with data available) and were included in the intention-to-treat population. The mean pain score change was -3.7 (95% CI, -4.2 to -3.2) in the ketamine group compared with -3.8 (95% CI, -4.2 to -3.4) in the morphine group. The difference in mean pain score change was 0.1 (95% CI, -0.7 to 0.9) points. There were no clinically meaningful differences for vital signs between the 2 groups. The intravenous morphine group had 19 of 113 (16.8% [95% CI, 10.4%-25.0%]) adverse effects reported (most commonly nausea [12 of 113 (10.6%)]) compared with 49 of 120 (40.8% [95% CI, 32.0%-49.6%]) in the ketamine group (most commonly emergence phenomenon [24 of 120 (20.0%)]). No adverse events required intervention. Conclusions and Relevance: In the KETAMORPH study of patients with out-of-hospital traumatic pain, the use of intravenous ketamine compared with morphine showed noninferiority for pain reduction. In the ongoing opioid crisis, ketamine administered alone is an alternative to opioids in adults with out-of-hospital traumatic pain. Trial Registration: ClinicalTrials.gov Identifier: NCT03236805.