Opioid-sparing Properties Research Articles

Low-pressure pneumoperitoneum with intraoperative dexmedetomidine infusion in laparoscopic cholecystectomy for enhanced recovery after surgery: A prospective randomised controlled clinical trial.

Enhanced Recovery After Surgery (ERAS) programs represent a shift in perioperative care, combining evidence-based interventions to reduce surgical stress to expedite recovery. ERAS requires cohesive team efforts to facilitate early discharge and reduce hospital stays. Anaesthesia and pneumoperitoneum management within ERAS play crucial roles in influencing postoperative outcomes. Laparoscopic cholecystectomy is widely acknowledged as the foremost approach for managing symptomatic gallstone disease due to its minimally invasive nature and favourable recovery. It has been demonstrated that increased abdominal pressures with prolonged CO2 exposure produce changes in cardio-vascular and pulmonary dynamics, which can be minimized by insufflating at minimum pressure required for adequate exposure, as advocated by European endoscopic guidelines. Dexmedetomidine, a highly selective alpha-2 adrenoreceptor agonist, has gained attention in anaesthesia armamentarium due to its sedative, analgesic, sympatholytic, and opioid-sparing properties. For multimodal opioid sparing postoperative pain management it's advantageous. To evaluate combined effect of low-pressure pneumoperitoneum and intra-operative dexmedetomidine infusion in laparoscopic cholecystectomy for ERAS. 160 patients of American Society of Anaesthesiologists (ASA) score 1 and 2, undergoing elective laparoscopic cholecystectomy were randomized into low pressure pneumoperitoneum (10-12 mmHg) and standard pressure pneumoperitoneum (13-15 mmHg) groups. Each group is subdivided into, no Dexmedetomidine (ND) and with Dexmedetomidine (WD) infusion (0.7 mcg/kg/hr) intra-operatively. Thus, 40 patients in each of the 4 study arms. Perioperative variables were collected and analysed. Low pressure pneumoperitoneum with intra-operative Dexmedetomidine infusion (0.7 mcg/kg/hr) resulted in stable hemodynamics, reduced post-operative pain, no requirement of additional analgesics and early discharge. Thus, synergistic impact of these interventions significantly improved postoperative outcomes when used as part of ERAS protocols.

Efficacy of memantine premedication in alleviating postoperative pain- A systematic review and meta-analysis.

Many premedication agents with opioid-sparing properties have been used in patients undergoing various elective surgeries. Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been used by many researchers as an opioid-sparing strategy. Various databases like PubMed, Scopus, Cochrane Library, and clinicaltrials.gov were searched after registering the review protocol in PROSPERO for randomized-controlled trials (RCTs) that investigated the efficacy and safety of memantine premedication in adult patients undergoing various elective surgeries. The risk of bias (RoB-2) scale was used to assess the quality of evidence. From the 225 articles that were identified after a database search, 3 studies were included for a qualitative systematic review and a quantitative meta-analysis. The pooled analysis revealed that the use of memantine provided better pain scores at 2nd (mean difference: -0.82, 95% CI: -1.60, -0.05, P = 0.04) with significant heterogeneity (P = 0.06; I² =71%), and 6 hours postoperatively (mean difference: -1.80, 95% CI: -2.23, -1.37, P < 0.00001), but not at 1 hour. The sedation scores at 1 hour were higher in the memantine group but comparable in the 2nd hour. The number of doses of rescue analgesia and nausea/vomiting in the postoperative period was comparable in both groups. The results of this review suggest that memantine premedication could provide better pain scores in the immediate postoperative period with acceptable adverse effects. However, the current evidence is insufficient to suggest the routine use of memantine as a premedication before elective surgeries.

Dexamethasone and dexmedetomidine as adjuvants to ropivacaine do not prolong analgesia in wound infiltration for lumbar spinal fusion: a prospective randomized controlled study

Background and objectivesLocal anesthetics (LAs) are widely used to infiltrate into surgical wounds for postoperative analgesia. Different adjuvants like dexamethasone and dexmedetomidine, when added to LA agents, could improve and prolong analgesia. The aim of this trial was to evaluate the analgesic efficacy and opioid-sparing properties of dexamethasone and dexmedetomidine when added to ropivacaine for wound infiltration in transforaminal lumbar interbody fusion (TLIF).MethodsWe conducted a controlled study among 68 adult patients undergoing TLIF, which was prospective, randomized and double-blind in nature. The participants were divided into four equal groups at random. Group R was given 150 mg of 1% ropivacaine (15 mL) and 15 mL of normal saline. Group R + DXM received 150 mg of 1% ropivacaine (15 mL) and 10 mg of dexamethasone (15 mL). Group R + DEX received 150 mg of 1% ropivacaine (15 mL) and 1 µg/kg of dexmedetomidine (15 mL). Lastly, group R + DXM + DEX was given 150 mg of 1% ropivacaine (15 mL), 10 mg of dexamethasone and 1 µg/kg of dexmedetomidine (15 mL). The primary focus was on the length of pain relief provided. Additionally, secondary evaluations included the amount of hydromorphone taken after surgery, the numerical rating scale and safety assessments within 48 h after the operation.ResultsBased on the p value (P > 0.05), there was no significant variance in the duration of pain relief or the total usage of hydromorphone after surgery across the four groups. Similarly, the numerical rating scale scores at rest and during activity at 6-, 12-, 24- and 48-h post-surgery for all four groups showed no difference (P > 0.05). However, the incidence of delayed anesthesia recovery was slightly higher in group R + DEX and group R + DXM + DEX when compared to group R or group R + DXM. Furthermore, there were no significant differences between the four groups in terms of vomiting, nausea, dizziness or delayed anesthesia recovery.ConclusionFor wound infiltration in TLIF, the addition of dexamethasone and dexmedetomidine to ropivacaine did not result in any clinically significant reduction in pain or opioid consumption and could prompt some side effects.

Ultrasound Guided Fascia Iliaca Compartment Block versus Three in One Block for Post Operative Analgesia in Patients Undergoing Hip and Knee Replacement Surgeries

Abstract Background Patients undergoing total hip and knee arthroplasty experience substantial and sustained postoperative pain. Inadequate analgesia may impede physical therapy and rehabilitative efforts and delay hospital dismissal. Peripheral nerve blockade of the lumbosacral plexus has emerged as an analgesic approach. In several studies, unilateral peripheral block provided quality of analgesia and functional outcomes similar to those of continuous epidural analgesia and superior to those of systemic analgesia, but with fewer side effects because of their opioid-sparing properties. Peripheral nerve block techniques may be the optimal analgesic method following total joint arthroplasty. Aim of the Work To compare postoperative analgesia between ultrasound-guided FICB and three in one nerve block. Study design a prospective randomized double-blinded study. Patients and Methods The study was conducted on 80 randomly chosen patients from 21 to 65 years old in Ain Shams University Hospitals after approval of the medical ethical committee. Patients were divided randomly into two groups, each group consisted of 40 patients group I and group II. After preoperative assessment and obtaining baseline vital data, all patients received spinal anesthesia. Patients in the group I received FICB (35-40 ml of 0.25% bupivacaine). Patients in group II received three in one bock (35-40 mL of bupivacaine 0.25%). Results Both FICB and three in one block provided good quality of postoperative analgesia and patient satisfaction as evidenced by low VAS and low postoperative rescue analgesic requirements. Both techniques provided equal sensory blockage of femoral nerve, obturator nerve, and genitofemoral nerve, but sensory blockage of LFC nerve was demonstrated in 92.5% patients in FICB and 62.5% of patients in three in one block, which was significantly lower (p-value &amp;lt;0.001 HS). VAS at 12 hours after surgery during movement of 3.68 ± 2.77 in the FICB group and 4.90 ±0.18 in the 3 in 1 group were statistically significant (P value = 0.007). Conclusion The FICB provides a high degree of sensory blockade of the LFC nerve and improves analgesia when continuous passive motion is initiated in the early postoperative period; also, it is easy to perform, reliable and does not threaten any vital organ. Thus, FICB can be recommended as an alternative to three in one block for the treatment of pain after hip and knee arthroplasty.

Emergency Palliative Cancer Care: Dexmedetomidine Treatment Experiences-A Retrospective Brief Report on Nine Consecutive Cases.

Dexmedetomidine, an alpha-2 adrenergic receptor agonist with potential opioid sparing properties, is utilized in palliative medicine, but the knowledge base for this practice is limited. We describe concomitant use of dexmedetomidine and opioids in an acute palliative care unit. We included all hospitalized palliative cancer care patients treated with dexmedetomidine from January 2019 to January 2021. Demographics, opioid doses, dexmedetomidine indications and dosing, reported effects and adverse responses, as well as treatment lengths were recorded. Three women and six men aged 42-66years with metastatic cancer and Eastern Cooperative Oncology Group (ECOG) performance status I-IV used dexmedetomidine and opioids concomitantly. Indications for dexmedetomidine were pain (n = 7) and anxiety (n = 2). Dexmedetomidine was administered intravenously in two patients and subcutaneously in seven. All administrations were continuous infusions; initial doses ranged from 240 to 1344µg/24h with later doses from 240 to 2440µg/24h. Physicians reported relief from pain and anxiety, but two patients required neuraxial pain management during admission. At day 2 of dexmedetomidine treatment, the opioid dose was reduced in six out of nine patients. For all patients with available data at day 7, mean opioid dose was reduced to 74% of the initial dose. When excluding the two patients requiring neuraxial pain management, the corresponding number was 80%. Two patients had transient hypotension, but dexmedetomidine was well tolerated and in no cases withdrawn due to adverse effects. Mean dexmedetomidine treatment length was 40days. Dexmedetomidine treatment decreased opioid consumption and was well tolerated in a retrospective study of nine palliative cancer care patients. It may represent a treatment option late in the disease trajectory.

A comprehensive overview of clinical research on dexmedetomidine in the past 2decades: A bibliometric analysis.

Introduction: Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist with sedative, analgesic, anxiolytic, and opioid-sparing properties. A large number of dexmedetomidine-related publications have sprung out in the last 2decades. However, no bibliometric analysis for clinical research on dexmedetomidine has been published to analyze hot spots, trends, and frontiers in this field. Methods: The clinical articles and reviews related to dexmedetomidine, published from 2002 to 2021 in the Web of Science Core Collection, were retrieved on 19 May 2022, using relevant search terms. VOSviewer and CiteSpace were used to conduct this bibliometric study. Results: The results showed that a total of 2,299 publications were retrieved from 656 academic journals with 48,549 co-cited references by 2,335 institutions from 65 countries/regions. The United States had the most publications among all the countries (n = 870, 37.8%) and the Harvard University contributed the most among all institutions (n = 57, 2.48%). The most productive academic journal on dexmedetomidine was Pediatric Anesthesia and the first co-cited journal was Anesthesiology. Mika Scheinin is the most productive author and Pratik P Pandharipande is the most co-cited author. Co-cited reference analysis and keyword analysis illustrated hot spots in the dexmedetomidine field including pharmacokinetics and pharmacodynamics, intensive care unit sedation and outcome, pain management and nerve block, and premedication and use in children. The effect of dexmedetomidine sedation on the outcomes of critically ill patients, the analgesic effect of dexmedetomidine, and its organ protective property are the frontiers in future research. Conclusion: This bibliometric analysis provided us with concise information about the development trend and provided an important reference for researchers to guide future research.

Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids

Cannabis has been proposed as a therapeutic with potential opioid-sparing properties in chronic pain, and its use could theoretically be associated with decreased amounts of opioids used and decreased risk of mortality among individuals prescribed opioids. To examine the risks associated with cannabis use among adults prescribed opioid analgesic medications. This cohort study was conducted among individuals aged 18 years and older who had urine drug screening in 2014 to 2019 and received any prescription opioid in the prior 90 days or long-term opioid therapy (LTOT), defined as more than 84 days of the prior 90 days, through the Veterans Affairs health system. Data were analyzed from November 2020 through March 2022. Biologically verified cannabis use from a urine drug screen. The main outcomes were 90-day and 180-day all-cause mortality. A composite outcome of all-cause emergency department (ED) visits, all-cause hospitalization, or all-cause mortality was a secondary outcome. Weights based on the propensity score were used to reduce confounding, and hazard ratios [HRs] were estimated using Cox proportional hazards regression models. Analyses were conducted among the overall sample of patients who received any prescription opioid in the prior 90 days and were repeated among those who received LTOT. Analyses were repeated among adults aged 65 years and older. Among 297 620 adults treated with opioids, 30 514 individuals used cannabis (mean [SE] age, 57.8 [10.5] years; 28 784 [94.3%] men) and 267 106 adults did not (mean [SE] age, 62.3 [12.3] years; P < .001; 247 684 [92.7%] men; P < .001). Among all patients, cannabis use was not associated with increased all-cause mortality at 90 days (HR, 1.07; 95% CI, 0.92-1.22) or 180 days (HR, 1.00; 95% CI, 0.90-1.10) but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.01-1.07) and 180 days (HR, 1.04; 95% CI, 1.01-1.06). Among 181 096 adults receiving LTOT, cannabis use was not associated with increased risk of all-cause mortality at 90 or 180 days but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.02-1.09) and 180 days (HR, 1.05; 95% CI, 1.02-1.09). Among 77 791 adults aged 65 years and older receiving LTOT, cannabis use was associated with increased 90-day mortality (HR, 1.55; 95% CI, 1.17-2.04). This study found that cannabis use among adults receiving opioid analgesic medications was not associated with any change in mortality risk but was associated with a small increased risk of adverse outcomes and that short-term risks were higher among older adults receiving LTOT.

Opioid-sparing Effects of the Nrf2 Activator Diroximel Fumarate in Mice

Opioids are still considered as a gold standard for the treatment of acute and chronic pain. However, their long-term administration can result in tolerance and paradoxical opioid-induced hyperalgesia (OIH). We hypothesized that activating the antioxidant transcription factor Nrf2 would alleviate morphine tolerance and OIH. Diroximel fumarate (DRF), an FDA approved drug, was used to activate Nrf2. For the OIH experiment, naïve mice were implanted with subcutaneous osmotic minipumps to infuse morphine dose for 7 days (10 mg/kg/day). Oral DRF (100 mg/kg/day) or vehicle was administered the day before minipump implantation, and then daily for the 7-day morphine infusion. For the tolerance experiment, naïve mice were administered with subcutaneous morphine (5 mg/kg/twice daily) or saline along with oral DRF (100 mg/kg/day) or vehicle for 5 days. On day 5, cumulative doses of morphine (1.8, 3.2, 5.6, 10.0 and 18.0 mg/kg) were injected after every 20 min. Withdrawal thresholds to heat and mechanical stimuli were assessed using hot plate tests and Von Freys, respectively. Male and female mice treated with morphine alone had decreased withdrawal thresholds to heat and mechanical stimuli by day 7, indicating development of OIH. However, DRF co-treatment blunted development of OIH. Mice treated with DRF alone did not show any change in withdrawal thresholds. Similarly, cumulative doses of morphine on day 5 caused a rightward shift in the dose response curve of morphine treated mice when compared to saline, showing development of tolerance. DRF co-treatment partially prevented development of tolerance. Expression of antioxidant genes/proteins in the spinal cord and brain will also be presented and Nrf2 positive cells identified. DRF has the potential to partially prevent the development of OIH and tolerance, thereby suggesting that DRF has opioid-sparing properties. Future studies will investigate the effects of DRF on other adverse effects of opioids. Grant support from NIH 1RF1NS113840-01. Opioids are still considered as a gold standard for the treatment of acute and chronic pain. However, their long-term administration can result in tolerance and paradoxical opioid-induced hyperalgesia (OIH). We hypothesized that activating the antioxidant transcription factor Nrf2 would alleviate morphine tolerance and OIH. Diroximel fumarate (DRF), an FDA approved drug, was used to activate Nrf2. For the OIH experiment, naïve mice were implanted with subcutaneous osmotic minipumps to infuse morphine dose for 7 days (10 mg/kg/day). Oral DRF (100 mg/kg/day) or vehicle was administered the day before minipump implantation, and then daily for the 7-day morphine infusion. For the tolerance experiment, naïve mice were administered with subcutaneous morphine (5 mg/kg/twice daily) or saline along with oral DRF (100 mg/kg/day) or vehicle for 5 days. On day 5, cumulative doses of morphine (1.8, 3.2, 5.6, 10.0 and 18.0 mg/kg) were injected after every 20 min. Withdrawal thresholds to heat and mechanical stimuli were assessed using hot plate tests and Von Freys, respectively. Male and female mice treated with morphine alone had decreased withdrawal thresholds to heat and mechanical stimuli by day 7, indicating development of OIH. However, DRF co-treatment blunted development of OIH. Mice treated with DRF alone did not show any change in withdrawal thresholds. Similarly, cumulative doses of morphine on day 5 caused a rightward shift in the dose response curve of morphine treated mice when compared to saline, showing development of tolerance. DRF co-treatment partially prevented development of tolerance. Expression of antioxidant genes/proteins in the spinal cord and brain will also be presented and Nrf2 positive cells identified. DRF has the potential to partially prevent the development of OIH and tolerance, thereby suggesting that DRF has opioid-sparing properties. Future studies will investigate the effects of DRF on other adverse effects of opioids. Grant support from NIH 1RF1NS113840-01.

Low-dose ketamine infusions reduce opioid use in pediatric and young adult oncology patients.

Ketamine is an NMDA-receptor antagonist with analgesic and opioid-sparing properties. Although well studied in adults, more robust evidence supporting ketamine's use for pediatric pain management is needed. This retrospective study evaluates ketamine's opioid-sparing effectiveness in pediatric and young adult oncology and hematology patients. Continuous ketamine infusions administered for pain management between 2010-2020 were reviewed. Data including demographic characteristics, oncology/hematology and pain diagnoses, concurrent pain medications, and ketamine infusions' dose and duration were collected. Opioid consumption data based on delivery via patient-controlled analgesia were collected 1 day before (D1), all days during (cumulatively named D2), and 1 day after (D3) ketamine infusions and calculated as morphine-equivalent doses (mg/kg/day). Data were reported for the entire study group as well as for distinct oncology and end-of-life categories, and short-term acute pain circumstances which included vaso-occlusive crises in hematology patients. Side effects were reviewed. Significantly lower daily opioid consumption was noted in the oncology group, while decreases were not significant in the end-of-life group and in the overall study population. The acute pain group did not show an opioid reduction associated with the ketamine infusions. A largely tolerable side-effect profile was observed, with no differences among each group's incidence. Ketamine infusions were associated with significantly reduced opioid consumption for oncology patients. The opioid-sparing effects of ketamine may vary according to clinical diagnoses and circumstances of use. Overall, low-dose ketamine infusions present an acceptable safety profile in pediatric and young adult patients; nevertheless, individual risks and benefits should be considered.

Recent Advances in the Clinical Value and Potential of Dexmedetomidine.

Dexmedetomidine, a highly selective α2-adrenoceptor agonist, has sedative, anxiolytic, analgesic, sympatholytic, and opioid-sparing properties and induces a unique sedative response which shows an easy transition from sleep to wakefulness, thus allowing a patient to be cooperative and communicative when stimulated. Recent studies indicate several emerging clinical applications via different routes. We review recent data on dexmedetomidine studies, particularly exploring the varying routes of administration, experimental implications, clinical effects, and comparative advantages over other drugs. A search was conducted on the PubMed and Web of Science libraries for recent studies using different combinations of the words “dexmedetomidine”, “route of administration”, and pharmacological effect. The current routes, pharmacological effects, and application categories of dexmedetomidine are presented. It functions by stimulating pre- and post-synaptic α2-adrenoreceptors within the central nervous system, leading to hyperpolarization of noradrenergic neurons, induction of an inhibitory feedback loop, and reduction of norepinephrine secretion, causing a sympatholytic effect, in addition to its anti-inflammation, sleep induction, bowel recovery, and sore throat reduction effects. Compared with similar α2-adrenoceptor agonists, dexmedetomidine has both pharmacodynamics advantage of a significantly greater α2:α1-adrenoceptor affinity ratio and a pharmacokinetic advantage of having a significantly shorter elimination half-life. In its clinical application, dexmedetomidine has been reported to present a significant number of benefits including safe sedation for various surgical interventions, improvement of intraoperative and postoperative analgesia, sedation for compromised airways without respiratory depression, nephroprotection and stability of hypotensive hemodynamics, reduction of postoperative nausea and vomiting and postoperative shivering incidence, and decrease of intraoperative blood loss. Although the clinical application of dexmedetomidine is promising, it is still limited and further research is required to enhance understanding of its pharmacological properties, patient selection, dosage, and adverse effects.

Nonopioid Analgesics in Postoperative Pain Management After Cardiac Surgery.

Opioid analgesia is still considered the standard of practice for cardiac surgery. In recent years, combinations of several nonnarcotic analgesics and regional analgesia have shown promise in restricting opioid use during and after cardiac surgery. Ketamine infusion, dexmedetomidine infusion, acetaminophen, ketorolac, and gabapentin are useful adjuvants in cardiac anesthesia practice and have opioid-sparing properties. The beneficial effects of nonnarcotic multimodal analgesia on intraoperative stress response, recovery profile, postoperative pain, and persistent opioid use after cardiac surgery are yet to be established, and further randomized clinical trials are required.

The association between dexmedetomidine as a single or adjuvant sedative versus other sedatives and the duration of mechanical ventilation and ICU stay in critically ill patients in a central South African ICU

Background: Sedation is often required in the intensive care unit (ICU) but can be harmful if administered inappropriately or excessively. Dexmedetomidine offers a favourable, cooperative sedation profile, despite a higher relative cost. It also has analgesic and opioid-sparing properties. The multidisciplinary ICU at our central South African hospital adopted the use of dexmedetomidine through the course of 2016. The aim of the study was to determine whether this change in practice affected the ICU length of stay (LOS) and duration of mechanical ventilation at this unit. Methods: A retrospective cohort analysis of patients’ files, who were sedated with midazolam and propofol in 2015 and those sedated with dexmedetomidine in 2017, was conducted. The data gathered included the sedatives used, demographic and vital data, ICU LOS, duration of mechanical ventilation and treatment of side effects. Group 2015 and Group 2017 were also analysed for possible confounders where appropriate, and these confounders were excluded for a re-analysis. Descriptive statistics were used and results were analysed for range, median, interquartile range (IQR), percentage and frequency. For post-hoc analysis of the effect of confounders, the Spearman rank correlation coefficient was used to determine the association between duration and sedative exposure and either duration of ICU stay or mechanical ventilation. The null hypothesis was set at p &lt; 0.05. Results: Group 2015 comprised 52 patients and Group 2017 60 patients. No difference between the groups was found regarding ICU LOS (median [IQR] 5 [2–14] vs 8.5 [5–12.5] days; p = 0.10) or mechanical ventilation (median [IQR] 91 [34–272] vs 129 [58–221] hours; p = 0.44). Those who were sedated with dexmedetomidine had better initial prognoses (median APACHE II score 13 vs 18, p = 0.01), were sedated for greater fractions of their total ICU stay (median 46% vs 25%, p &lt; 0.01), and had a higher incidence of hypotension and bradycardia (36.7% vs 11.4%; p &lt; 0.01); which did not relate to a higher mortality. Spearman’s rank correlation coefficients also showed a weak to moderate association with longer ICU stay and ventilation duration when the duration of sedation with midazolam or propofol was shorter in relation to ICU stay. Conclusion: We did not find a reduction in ICU LOS or mechanical ventilation with the advent of dexmedetomidine in our unit. The lack of regular documentation of sedation levels and scheduled sedation breaks might have contributed to these results. Dexmedetomidine has a role to play in the ICU setting, but it should only be used when clearly indicated. Vigilance for hypotension and bradycardia is required when using dexmedetomidine.

Efficacy of Dexmedetomidine Infusion to Attenuate Hemodynamic Response and Opioid Sparing Properties During Wide Excision of Carcinoma Tongue

After Institutional Ethics Committee approval, 20 American Society of Anesthesiologists'-physical status (ASA-PS) I-II patients with carcinoma tongue scheduled for WLE of tongue lesion were enrolled randomly for this study. One group was offered standard intraoperative management (control group) while other (Test group) Dexmedetomidine infusion was used.

Analgesic efficacy of ketamine and magnesium after laparoscopic sleeve gastrectomy: A randomized, double-blind, placebo-controlled trial

BackgroundKetamine and magnesium are antagonists of the N-methyl-d-aspartate receptor, and are valuable adjuvants for multimodal analgesia and opioid sparing. Data are limited regarding the opioid sparing efficacy of the combined intraoperative application of these agents in laparoscopic bariatric surgery. The objective of this study was to compare the postoperative opioid sparing properties of a single intraoperative dose of ketamine versus a combination of single doses of ketamine and magnesium after laparoscopic gastric sleeve resection in bariatric patients.MethodsOne hundred and twenty- six patients were randomly assigned to receive single boluses of ketamine alone 0.5 mg kg−1 IV (ketamine group); combined ketamine bolus of 0.5 mg kg−1 IV and magnesium 2 g IV (ketamine and magnesium group); or placebo. Opioid consumption at 24 h (in morphine equivalents); pain at rest; postoperative nausea and vomiting impact score; sedation scores; and trends of transcutaneous carbon-di-oxide values were analysed.ResultsThe median (inter-quartile range [range]) morphine consumption at 24 h were 32 (24–47 [4.8–91]) mg in the ketamine group, 37 (18–53 [1–144]) mg in the ketamine and magnesium group, and 26 (21–36 [5–89]) mg in the control group and were not significantly different between the groups. There were no differences for all other outcomes examined.ConclusionCombined single intraoperative bolus doses of ketamine and magnesium did not result in postoperative opioid sparing after laparoscopic gastric sleeve resection.

Opioid-free recovery after herniorrhaphy with HTX-011 as the foundation of a multimodal analgesic regimen

BackgroundMost severe pain occurs within the first 72 hours after an operation, and current local anesthetics have a limited duration of action. HTX-011 is a dual-acting, local anesthetic containing bupivacaine, and low-dose meloxicam in an extended-release polymer. In a prior phase 3 inguinal herniorrhaphy study, HTX-011 alone provided superior pain relief for 72 hours and significantly decreased opioid use compared with saline placebo and bupivacaine hydrochloride. This open-label study assessed the safety, efficacy, and opioid-sparing properties of HTX-011 as the foundation of a scheduled, nonopioid, multimodal analgesia regimen in patients undergoing open inguinal herniorrhaphy. MethodsThis study was conducted in 2 sequential cohorts. All patients received a single, intraoperative dose of HTX-011 prior to wound closure, followed by a scheduled postoperative regimen of oral ibuprofen and acetaminophen for 72 hours. Patients in cohort 2 also received a single intraoperative dose of ketorolac. Opioid analgesics were available by request only. ResultsMore than 90% of patients remained opioid-free through 72 hours postoperatively, and 83% of patients remained opioid-free through day 28 (last study visit). Pain was well controlled, and mean intensity of the pain never increased higher than the mild range during the first 72 hours. Ketorolac did not demonstrate any additional benefit. HTX-011 with this multimodal analgesia regimen was well tolerated. ConclusionHTX-011 when used as the foundation of a nonopioid, multimodal analgesia regimen, provided effective and well-tolerated analgesia without the need for opioids in the majority of patients recovering from an open inguinal herniorrhaphy.

Intravenous ketorolac is associated with reduced mortality and morbidity after open abdominal aortic aneurysm repair.

The role of non-steroidal anti-inflammatory drugs in aortic aneurysm disease has been debated. Animal studies demonstrated that intrathecal ketorolac reduces the inflammatory response associated with aortic clamping. However, no human-subject study evaluated this association. Therefore, we sought to explore the effects of ketorolac use in open abdominal aortic aneurysm repair. The Premier Healthcare Database (June 2009-March 2015) was inquired to capture patients who underwent open abdominal aortic aneurysm repair for non-ruptured abdominal aortic aneurysm, identified via International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. Intravenous ketorolac was coded as any or none. Outcomes were in-hospital mortality, cardiac, respiratory, renal, neurological, and hemorrhagic complications. Multivariable logistic regression coarsened exact matching followed by conditional fixed-effect regression modeling were performed. A total of 6394 patients were identified (ketorolac: 806; 12.6%). Patients who received ketorolac were younger and less likely to have hypertension (76.1% vs. 79.3%), diabetes mellitus (12.5% vs. 17.4%), or chronic kidney disease (8.3% vs. 21.4%; all p values ≤ .033). There was no significant difference in medication use including oral non-steroidal anti-inflammatory drugs and malignant or musculoskeletal diseases. Mortality, respiratory, and renal complications were less prevalent with ketorolac (2.5% vs. 4.9%, 25.2% vs. 34.6%, 10.0% vs. 21.1%; p ≤ .002). Ketorolac was associated with lower adjusted odds for those events: 0.58 (0.36-0.93), 0.53 (0.42-0.68), and 0.72 (0.60-0.86), respectively (all p values ≤ .025). There was no association with neurological, cardiac, or hemorrhagic complications. The findings were replicated by coarsened exact matching analysis. This study demonstrated 40% mortality reduction with intravenous ketorolac following open abdominal aortic aneurysm repair. The survival benefit could be due to its anti-inflammatory and opioid-sparing properties. This is evident by its protective effect against respiratory outcomes. The lack of association with the classical non-steroidal anti-inflammatory drugs-related cardiac and hemorrhagic complication could be attributable to the short-term use of ketorolac compared with non-steroidal anti-inflammatory drugs chronic use.

A prospective randomized controlled study of combined spinal-general anesthesia vs. general anesthesia for laparoscopic gynecological surgery: Opioid sparing properties

Study objectiveWe aimed to determine the magnitude of peri-operative opioid sparing effect when general anesthesia is combined with spinal analgesia for laparoscopic gynecological surgery. DesignA prospective randomized controlled study; a three-group trial with two comparisons (each intervention group to control). SettingOperating room and postoperative recovery area. PatientsPatients aged between 18 and 65 years with American Society of Anesthesiologists physical status 1 or 2 who were scheduled for inpatient elective laparoscopic gynecological surgery with expected pneumoperitoneum duration of at least 20 min. Of 102 randomized patients, 99 completed the study. InterventionsPatients were randomized to general anesthesia alone (control group) or combined with very-low-dose (levobupivacaine 3.75 mg; sufentanil 2.5 μg) or low-dose (levobupivacaine 7.5 mg; sufentanil 2.5 μg) spinal analgesia. MeasurementsPrimary endpoints were perioperative opioid consumption and pain scores (11-point numeric rating scale) at 30 min, 1 h, 2 h, 4 h and 24 h post-surgery. Secondary endpoints were patient satisfaction with anesthetic care and participation in research, sevoflurane consumption and adverse effects. Main resultsIntra-operative sufentanil (median [95% CI]) consumption was 16.1 (10.5–22.6) μg/h in the control group versus 4.7 (3.2–9.2) μg/h in the very-low-dose and versus 2.9 (0.0–4.0) μg/h in the low-dose spinal analgesia groups (p < 0.001, for both comparisons). Median (95% CI) piritramide consumption at 24 h post-surgery was 7.5 (3–8) mg in the control group versus 5 (0–7.5) mg in the very-low dose spinal analgesia group (p = 0.182) and versus 2 (0–2.5) mg in the low-dose spinal analgesia group (p = 0.001). Postoperative pain scores were consistently <3 only in the low dose spinal analgesia group. Patient satisfaction with anesthetic care and participation in research was very high in all groups. ConclusionsLow-dose spinal analgesia in combination with general anesthesia reduces peri-operative opioid consumption in laparoscopic gynecological surgery in immediate postoperative period.

Low-Dose Dexmedetomidine Accelerates Gastrointestinal Function Recovery in Patients Undergoing Lumbar Spinal Fusion

Background: Dexmedetomidine possesses sedative, sympatholytic, and opioid-sparing properties, but its impact on postoperative gastrointestinal function is controversial. Methods: This single-center, prospective, randomized study compared low-dose dexmedetomidine and placebo on gastrointestinal function recovery and inflammation after posterior lumbar spinal fusion. Sixty-six patients were randomized into two groups and received normal saline (control group) or dexmedetomidine (DEX group) during posterior lumbar fusion. Blood was taken at five timepoints to measure lipopolysaccharides, tumor necrosis factor-α, and C-reactive protein. The primary outcome was duration to first flatus. The secondary outcomes were inflammatory mediators and determination of correlations between perioperative factors and duration to first flatus. Results: Patients in DEX group showed significantly lower duration to first flatus (15.37 [13.35–17.38] vs 19.58 [17.31–21.86] h; p = 0.006) and overall sufentanil consumption (67.19 [63.78–70.62] vs 74.67 [69.96–79.30] μg; p = 0.011) than controls. Lipopolysaccharides, tumor necrosis factor-α, and C-reactive protein did not differ between the groups at any timepoint (all p > 0.05). Multiple linear regression modeling assessed the ability of independent variables to predict variance in duration to first flatus (adjusted R2 = 0.379, p = 0.000). In the model, age (β = 0.243, p = 0.003), gender (β = −3.718, p = 0.011), BMI (β = −0.913, p = 0.001), operative segments (β = −4.079, p = 0.028), and overall sufentanil consumption (β = 0.426, p = 0.000) contributed significantly. Conclusions: Thus, low-dose dexmedetomidine accelerates gastrointestinal function recovery after lumbar spinal fusion. The effect may be partially produced by opioid-sparing effects rather than inhibition of inflammation. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR1800018127.

Cannabinoids and Pain Management: an Insight into Recent Advancements

This review discusses the recent advancements in research on Cannabinoids’ role in pain, including its use in cancer pain, neuropathic pain, fibromyalgia, headache, visceral pain, postoperative and failed back pain management, and concurrent use with opioids. Current research suggests that a potential role exists for medical cannabis in pain management, although research shows varied effectiveness by the type of pain. Moreover, its coadministration with opioids may result in reduced opioid requirements. Patients with neuropathic pain, cancer pain, and migraine headache may benefit from the analgesic effects of a cannabis-based medicine (CBM), but not necessarily patients with chronic abdominal pain. Equivocal results were shown in fibromyalgia and postoperative orthopedic pain. Interestingly, the opioid-sparing properties of CBM make it an attractive option for pain management. However, the scale and quality of studies conducted are limited. Further research is necessary to establish recommendation guidelines for medical cannabis in pain management.

Dexmedetomidine: present and future directions

Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist, with sedative, analgesic, anxiolytic, sympatholytic, and opioid-sparing properties. Dexmedetomidine induces a unique sedative response, which shows an easy transition from sleep to wakefulness, thus allowing a patient to be cooperative and communicative when stimulated. Dexmedetomidine may produce less delirium than other sedatives or even prevent delirium. The analgesic effect of dexmedetomidine is not strong; however, it can be administered as a useful analgesic adjuvant. As an anesthetic adjuvant, dexmedetomidine decreases the need for opioids, inhalational anesthetics, and intravenous anesthetics. The sympatholytic effect of dexmedetomidine may provide stable hemodynamics during the perioperative period. Dexmedetomidine-induced cooperative sedation with minimal respiratory depression provides safe and acceptable conditions during neurosurgical procedures in awake patients and awake fiberoptic intubation. Despite the lack of pediatric labelling, dexmedetomidine has been widely studied for pediatric use in various applications. Most adverse events associated with dexmedetomidine occur during or shortly after a loading infusion. There are some case reports of dexmedetomidine-related cardiac arrest following severe bradycardia. Some extended applications of dexmedetomidine discussed in this review are promising, but still limited, and further research is required. The pharmacological properties and possible adverse effects of dexmedetomidine should be well understood by the anesthesiologist prior to use. Moreover, it is necessary to select patients carefully and to determine the appropriate dosage of dexmedetomidine to ensure patient safety.