Intrathecal Administration Of Morphine Research Articles

Effects of Intrathecal Morphine Administration in Patients Undergoing Primary Total Hip Arthroplasty Under Spinal Anesthesia With Quadratus Lumborum Block for Postoperative Analgesia.

Introduction Quadratus lumborum (QL) block has previously been shown to provide improved analgesia in patients undergoing primary total hip arthroplasty (THA) under spinal anesthesia when compared to spinal anesthesia alone. Additionally, recent studies have shown the addition of intrathecal morphine (ITM) to provide superior postoperative analgesia in patients undergoing various surgical interventions including total knee arthroplasty under spinal anesthesia with peripheral nerve blockade. At this time, however, there has not been a study evaluating the effects of intrathecal morphine in patients undergoing THA under spinal anesthesia with QL block. This study aims to assess if the addition of intrathecal morphine can provide adequate or even superior postoperative analgesia in patients undergoing primary THA. Methods This retrospectivestudyincluded 26 patients in the spinal/QL block/intrathecal morphine (SA+QLB+ITM) group, 31 patients in the spinal/QL block group (SA+QLB), and 28 patients in the spinal only (SA or control) group. Twenty-six patients undergoing primary THA under a combination of spinal anesthesia and peripheral nerve blockade (quadratus lumborum block) were given a dose of 100 mcg of intrathecal morphine. Various parameters were evaluated including Post-Anesthesia Care Unit (PACU) and 24-hour visual analog scale (VAS) scores, time to first opioid use, 24- and 48-hour total opioid use as oral morphine equivalents (OME), 24-hour ambulation distance, and time from block placement to hospital discharge. The results were analyzed and compared to patients undergoing primary THA under spinal anesthesia with QL block (no intrathecal morphine) and compared to a control group of patients undergoing primary THA under spinal anesthesia only. Results The study analysis included 26 patients in the SA+QLB+ITM group, 31 patients in the SA+QLB group, and 28 patients in the SA (control) group. When compared with the control group, the SA+QLB+ITM had lower 24-hour total opioid usage (mean difference 20.80 OME, CI 6.454 to 35.15, p-value 0.0025), longer time to 1st opioid use (mean difference -20.51 hours later, p-value .0052), lower 24-hr VAS (difference 2.421, p-value 0.0012, CI 0.8559 to 3.987), and faster time to discharge (16.00 hr earlier, p-value 0.0459). When compared to the SA+QLB group, the SA+QLB+ITM group only showed a statistically significant difference in faster time to discharge (19.46 hr earlier, p-value 0.0068). However, while there was no statistically significant difference in time to 1st opioid use between the control and SA+QLB group, the difference did become significant when comparing the control to the SA+QLB+ITM group (mean difference -20.51 hours later (p-value .0052). There was no significant difference in either of the three groups in ambulation distance at 24 hours, PACU VAS, or 48-hour total opioid use. Conclusion Our study concludes that the addition of 100 mcg ITM for total hip arthroplasty under spinal anesthesia improved postoperative analgesia compared to the control group. Also, the ITM group did better with respect to delay in first opioid use and decreased hospital stay compared to the control and block-only groups. Our study warrants no more concerns of PONV, pruritus, or respiratory depression with this dose of ITM and requires standard postoperative care.

Inhibition of spinal BRD4 alleviates pyroptosis and M1 microglia polarization via STING-IRF3 pathway in morphine-tolerant rats

BackgroundMorphine tolerance has been a challenging medical issue. Neuroinflammation is considered as a critical mechanism for the development of morphine tolerance. Bromodomain-containing protein 4 (BRD4), a key regulator in cell damage and inflammation, participates in the development of chronic pain. However, whether BRD4 is involved in morphine tolerance and the underlying mechanisms remain unknown. MethodsThe morphine-tolerant rat model was established by intrathecal administration of morphine twice daily for 7 days. Behavior test was assessed by a tail-flick latency test. The roles of BRD4, pyroptosis, microglia polarization and related signaling pathways in morphine tolerance were elucidated by Western blot, real-time quantitative polymerase chain reaction, and immunofluorescence. ResultsRepeated morphine administration upregulated BRD4 level, induced pyroptosis, and promoted microglia M1-polarization in spinal cord, accompanied by the release of proinflammatory cytokines, such as TNF-α and IL-1β. JQ-1, a BRD4 antagonist, alleviated the development of morphine tolerance, diminished pyroptosis and induced the switch of microglia from M1 to M2 phenotype. Mechanistically, stimulator of interferon gene (STING)- interferon regulatory factor 3 (IRF3) pathway was activated and the protective effect of JQ-1 against morphine tolerance was at least partially mediated by inhibition of STING-IRF3 pathway. ConclusionThis study demonstrated for the first time that spinal BRD4 contributes to pyroptosis and switch of microglia polarization via STING-IRF3 signaling pathway during the development of morphine tolerance, which extend the understanding of the neuroinflammation mechanism of morphine tolerance and provide an alternative strategy for the precaution against of this medical condition.

Effect of Intrathecal Morphine on Postdural Puncture Headache in Obstetric Anaesthesia.

Intrathecal morphine is used as an effective component of multimodal analgesia in postoperative analgesia in cesarean section patients. We aimed to analyze the relationship between intrathecal morphine administration and postdural puncture headache (PDPH), pain score and analgesia consumption in the postoperative period, and maternal fetal effects. One hundred four pregnant women aged ≥18 years (American Society of Anesthesiology physical status I or II, >36 weeks gestation) who were scheduled for elective cesarean section under spinal anaesthesia were included in this study. Spinal anesthesia consisted of bupivacaine with or without morphine (Group M: 10 mg heavy marcaine + 25 mcg fentanyl + 100 mcg morphine; Group F: 10 mg heavy marcaine + 25 mcg fentanyl). The effect of intrathecal morphine on PDPH, postoperative pain score, analgesia consumption, and maternal and fetal effects were recorded for 5 days. PDPH developed in a total of 33 patients (Group M: 18 and Group F: 15, P=0.274). When we evaluated PDPH with the VAS, there was no significant difference between the groups. The postoperative visual analogue scale (VAS) was lower in the morphine group, and no statistically significant difference was found in the VAS 1st hr and VAS 2nd hr, whereas the VAS 6th hr and VAS 24th hr were found to be statistically significant. There was no difference in terms of PDPH, the first analgesic requirement and postoperative nausea-vomiting, but meperidine consumption was lower in the morphine group. Low-dose intrathecal morphine did not affect the incidence of PDPH. It is an effective method that can be used in cesarean section patients without increasing the maternal and fetal side effects from postoperative analgesia.

Blended (Combined Spinal and General) vs. General Anesthesia for Abdominal Hysterectomy: A Retrospective Study.

Adequate pain management for abdominal hysterectomy is a key factor to decrease postoperative morbidity, hospital length of stay and chronic pain. General anesthesia is still the most widely used technique for abdominal hysterectomy. The aim of this study was to assess the efficacy and safety of blended anesthesia (spinal and general anesthesia) compared to balanced general anesthesia in patients undergoing hysterectomy with or without lymphadenectomy for ovarian, endometrial or cervical cancer or for fibromatosis. We retrospectively collected data from adult ASA 1 to 3 patients scheduled for laparoscopic or mini-laparotomic hysterectomy with or without lymphadenectomy for ovarian, endometrial or cervical cancer or for fibromatosis. Exclusion criteria were age below 18 years, ASA > 3, previous chronic use of analgesics, psychiatric disorders, laparotomic surgery with an incision above the belly button and surgery extended to the upper abdomen for the presence of cancer localizations (e.g., liver, spleen or diaphragm surgery). The cohort of patients was retrospectively divided into three groups according to the anesthetic management: general anesthesia and spinal with morphine and local anesthetic (Group 1), general anesthesia and spinal with morphine (Group 2) and general anesthesia without spinal (Group 3). NRS was lower in the spinal anesthesia groups (Groups 1 and 2) than in the general anesthesia group (Group 3) for every time point but at 48 h. The addition of local anesthetics conferred a small but significant NRS decrease (p = 0.009). A higher percentage of patients in Group 3 received intraoperative sufentanil (52.2 ± 18 mcg in Group 3 vs. Group 1 31.8 ± 16.2 mcg, Group 2 44.1 ± 15.6, p < 0.001) and additional techniques for postoperative pain control (11.4% in Group 3 vs. 2.1% in Group 1 and 0.8% in Group 2, p < 0.001). Intraoperative hypotension (MAP < 65 mmHg) lasting more than 5 min was more frequent in patients receiving spinal anesthesia, especially with local anesthetics (Group 1 25.8%, Group 2 14.6%, Group 3 11.6%, p < 0.001), with the resulting increased need for vasopressors. Recovery-room discharge criteria were met earlier in the spinal anesthesia groups than in the general anesthesia group (Group 1 102 ± 44 min, Group 2 91.9 ± 46.5 min, Group 3 126 ± 90.7 min, p < 0.05). No differences were noted in postoperative mobilization or duration of ileus. Intrathecal administration of morphine with or without local anesthetic as a component of blended anesthesia is effective in improving postoperative pain control following laparoscopic or mini-laparotomic hysterectomy, in reducing intraoperative opioid consumption, in decreasing postoperative rescue analgesics consumption and the need for any additional analgesic technique. We recommend managing postoperative pain with a strategy tailored to the patient's physical status and the type of surgery, preventing and treating side effects of pain treatments.

Efficacy of intrathecal morphine administration in pediatric patients undergoing selective dorsal rhizotomy.

The purpose of this study was to evaluate the effectiveness of intrathecal morphine following selective dorsal rhizotomy in pediatric patients previously diagnosed with cerebral palsy. This was a retrospective, cohort analysis over the course of four years. The analysis consisted of a treatment group which received intrathecal morphine (5 mcg/kg) injection and a control group that did not receive the injection prior to dural closure. All patients underwent multilevel laminectomies for selective dorsal rhizotomy at Akron Children's Hospital. The effectiveness of the treatment was measured by total dose of hydromorphone administered on patient-controlled analgesia (PCA), number of days on oral narcotics, and cumulative dose of oral narcotic. Of the analyzed 15 pediatric patients, seven patients received intrathecal morphine injection while the other eight did not receive the treatment prior to dural closure. There was a difference of 1135 mcg in total PCA dose between the study group (3243 mcg) and the control group (4378 mcg). The total PCA dose based on weight was lower in the study group (163 mcg/kg) than in the control group (171 mcg/kg). Based on these findings, the administration of intrathecal morphine clinically reduces the opiate need in the first 96 hours post-operatively.

Effects of intrathecally administered interferon α on chronic constriction injury model rats' mechanical pain threshold and G protein expression in the spinal cord.

The aim of the study was to explore the analgesic mechanism of effects of intrathecally administered interferon a (IFN-a) on chronic constriction injury (CCI) model rats. 24 rats were divided into 6 groups, with 4 rats in each group, including the negative control group (Group N, no operation or treatment), the sham operation group (Group S, only the left sciatic nerve of the rats was exposed without ligation, 0.9% NaCl was intrathecally administered), and four experimental groups (CCI model was established first and then different drugs were intrathecally administered respectively), including 0.9% NaCl (Group C), IFN-a (Group CI), morphine (Group CM), and IFN-a combined with morphine (Group CIM). The mRNA levels of G proteins in both the spinal cord and dorsal root ganglia (DRG), as well as the content of amino acid and chemokine (C-X-C motif) ligand 6 (CXCL-6) in the cerebrospinal fluid were measured and analysed in each group. Intrathecal administration of IFN-a increased the mechanical pain threshold in CCI rats (33.32 ±1.36 vs. 21.08 ±1.59, p < 0.001), achieving the effect comparable to that of morphine (33.32 ±1.36 vs. 32.44 ±3.18, p > 0.05), increased the mRNA expression level of Gi protein (0.62 ±0.04 vs. 0.49 ±0.05, p = 0.006), and decreased the mRNA expression level of Gs protein in the spinal cord (1.80 ±0.16 vs. 2.06 ±0.15, p = 0.035) and DRG (2.11 ±0.10 vs. 2.79 ±0.13, p < 0.001). The intrathecal administration of both IFN-a and morphine can reduce the glutamate content in the cerebrospinal fluid (261.55 ±38.12 vs. 347.70 ±40.69, p = 0.012), but without any statistically significant difference in the content of CXCL-6 across all groups ( p > 0.05). Intrathecal injection of IFN-a improved the mechanical pain threshold in CCI rats, so we inferred that intrathecal administration of IFN-a had analgesic effects on neuropathic pain, possibly related to the activation of G-proteincoupled µ receptors in the spinal cord and the inhibition of glutamate release.

Early Warning System Triggers In Intensive Care Unit After Receiving Intrathecal Morphine: A Retrospective Analysis

Background: Neuraxial analgesia, including intrathecal morphine(ITM) administration, provides excellent analgesia in the post-abdominal surgery setting. As a corollary, such patients are commonly admitted to HDU/ICU for post-operative monitoring, and as such, bed availability can curtail its use. Reluctance to ward based postoperative care for this cohort is evident. Ward based postoperative care could benefit post-operative analgesic management.

Efficacy and Side Effect Profile of Intrathecal Morphine versus Distal Femoral Triangle Nerve Block for Analgesia following Total Knee Arthroplasty: A Randomized Trial

(1) Background: The management of postoperative pain after knee replacement is an important clinical problem. The best results in the treatment of postoperative pain are obtained using multimodal therapy principles. Intrathecal morphine (ITM) and single-shot femoral nerve block (SSFNB) are practiced in the treatment of postoperative pain after knee replacement, with the most optimal methods still under debate. The aim of this study was to compare the analgesic efficacy with special consideration of selected side effects of both methods. (2) Materials and methods: Fifty-two consecutive patients undergoing knee arthroplasty surgery at the Department of Orthopedics and Traumatology of the Medical University of Warsaw were included in the study. Patients were randomly allocated to one of two groups. In the ITM group, 100 micrograms of intrathecal morphine were used, and in the SSFNB group, a femoral nerve block in the distal femoral triangle was used as postoperative analgesia. The other elements of anesthesia and surgery did not differ between the groups. (3) Results: The total dose of morphine administered in the postoperative period and the effectiveness of pain management did not differ significantly between the groups (cumulative median morphine dose in 24 h in the ITM group 31 mg vs. SSFNB group 29 mg). The incidence of nausea and pruritus in the postoperative period differed significantly in favor of patients treated with a femoral nerve block. (4) Conclusions: Although intrathecal administration of morphine is similarly effective in the treatment of pain after knee replacement surgery as a single femoral triangle nerve block, it is associated with a higher incidence of cumbersome side effects, primarily nausea and pruritus.

The effect of intraoperative intrathecal opioid administration on the length of stay and postoperative pain control for patients undergoing lumbar interbody fusion.

In an effort to control postoperative pain more effectively in spinal fusion patients, intraoperative intrathecal morphine (ITM) administration is gaining popularity and acceptance with clinicians. This study seeks to determine the impact of intraoperative intrathecal opioid (ITO) administration following lumbar fusion surgery on postoperative pain and length of hospitalization as primary outcomes. Secondary outcomes will investigate postoperative opioid intake and side effects. The retrospective analysis of collected data was performed. The study compared patients undergoing one- or two-level transforaminal interbody fusions between 2019 and 2021 who intraoperatively received two different ITO doses (n = 89) vs. the reference group (n = 48) that did not receive ITO. The patients in the ITO group received either 0.2mg (n = 44) of duramorph or 0.2mg duramorph + 50 mcg fentanyl (n = 45). The effect of ITO was evaluated for the first four postoperative days (POD) on pain scores (visual analog scale), length of stay (LOS, hours) and opioid requirement (MED, morphine equivalent dose). In the ITO group, a significant reduction of postoperative pain scores (t(99) = 4.3,p < 0.001) and opioid intake (t(70) = 2.49,p = 0.015) was noted on POD1. Cohen's d effect sizes were 0.76 and 0.50, meaning that postoperative pain and MED intake were reduced by about ¾ to ½ standard deviations (SD) in the ITO group. Further, multivariate regression models revealed that ITO administration predicted lower postoperative pain scores for the two PODs (β = - 0.83, p < 0.001; β = - 0.63, p = 0.022) and MED intake for the first two PODs (β = - 20.8, p = 0.047; β = - 16.4, p = 0.030). Mean LOS was 15.4h less in the ITO group (mean ± SD, 63.4 ± 37.1 vs. 78.8 ± 39.6, p = 0.10). In conclusion, our study provides results in a large sample of patients undergoing transforaminal lumbar fusions. The results demonstrated that ITO administration is effective in reducing POD1 pain scores and POD1-2 opioid requirement while not increasing the risk of any opioid-related side effects.

Intravenous ondansetron reduced nausea but not pruritus following intrathecal morphine in children: Interim results of a randomized, double-blinded, placebo-control trial.

Study ObjectiveThis study's purpose was to determine if ondansetron can prevent pruritus after administration of intrathecal morphine in children, as has been demonstrated in adults.DesignA double‐blinded, randomized placebo‐controlled trial.SettingOperating room and first 24 h postoperative inpatient stay at an academic children's hospital.PatientsForty‐six children aged 3–17 years, who received 4–5 mcg/kg intrathecal morphine for urological or orthopedic procedures were included.InterventionsChildren were randomized to receive intravenous ondansetron (treatment) or saline placebo (placebo), prior to intrathecal morphine administration, and q6H for 24 h thereafter. Intraoperative anti‐emetics and postoperative rescue treatments for pruritus and nausea were standardized.MeasurementsPatients were interviewed q6H for scored pruritus, nausea, and pain, using standardized scales.Main ResultsThe trial was terminated for futility after interim analysis. Forty‐six children were recruited and 45 completed data collection. No significant difference was found between both groups for incidence of pruritus (requiring treatment) [relative risk (RR) 0.9, 95% CI: 0.7, 1.2], during the first postoperative 24 h. Notably, the incidence of pruritus was 84% overall, much higher than rates in previously published studies. Intravenous ondansetron significantly reduced the incidence of nausea, compared with the placebo group [RR 0.5, 95% CI: 0.3, 0.9].ConclusionsThis study found no evidence for intravenous ondansetron as an effective preventative for pruritus following intrathecal morphine in children. However, this RCT did find that the rate of pruritus following intrathecal morphine administration may be significantly higher than previously thought. Nausea and vomiting (a secondary outcome) were reduced significantly in the treatment group. The negative findings of this study reinforce the potential dangers of extrapolating the drug effects seen in adults onto pediatric patients.

Intraoperative administration of systemic/epidural/intrathecal morphine on the quality of recovery following substitutional urethroplasty with buccal mucosal graft: A randomized control trial.

Substitutional urethroplasty with buccal mucosal grafting for urethral stricture is associated with significant pain, and thus inappropriate perioperative pain management could delay postoperative recovery. The objective of our research was to determine the effects of analgesia with systemic or epidural or intrathecal morphine on quality of recovery (QoR) in patients undergoing substitutional urethroplasty with buccal mucosal grafting. This prospective, double-blinded, randomized control trial was conducted over 2 years in ASA I and II patients who underwent substitutional urethroplasty with buccal mucosal graft. Patients were randomized into three groups, and Group A received systemic morphine (0.1 mg/kg), Group B received epidural morphine (3 mg), and Group C received intrathecal morphine (150 μg). The QoR between the groups were compared postoperatively using the 40-item QoR questionnaire, and the hemodynamic variations, time taken for ambulation, resumption of oral intake, and incidence of complications were also compared. Out of the recruited 93 patients, 88 patients were analyzed. The QoR score for each domain was comparable between the three groups. The total QoR score for systemic, epidural, and intrathecal morphine groups were 189 (185-191), 189 (187-191), and 185 (183-189), respectively. Additionally, the hemodynamic variations, time taken for ambulation, and resumption of oral intake were comparable between all three groups except the incidence of postoperative nausea and vomiting (PONV) and pruritis, which were higher in the intrathecal group. All three modalities, namely systemic morphine (0.1 mg/kg), epidural morphine (3 mg), and intrathecal morphine (150 μg), offer similar QoR after substitutional urethroplasty. However, the incidence of PONV and pruritis was higher with the administration of intrathecal morphine.

Enhanced recovery after gynecological surgery: comparison between intrathecal and intravenous morphine multimodal analgesia.

The purpose of the present study was to compare the effectiveness of intrathecal injection of morphine, inserted in the protocols of multimodal analgesia, versus intravenous morphine in the control of postoperative pain and course in women undergoing gynecological surgery. An observational, single-center, retrospective and case-controlled study was performed. Data were collected in a group of women (N.=80) who underwent to gynecological surgery. Women were divided into two groups: group A (40 patients) laparoscopic hysterectomy and group B (N.=40) performing laparotomic myomectomy. In both groups 20 patients underwent administration of intrathecal morphine (125 mcg in 5 mL) and 20 patients underwent to intravenous morphine (1 mg maximum every 10 minutes). The primary endpoint collected was the mean VAS Score during the first 3 days after surgery, while secondary endpoints were opioid consumed during the same period, nausea, vomitus and pruritus. Among the exploratory objectives, length of hospital stay, canalization and feeding time were collected. In group A, patients performing intrathecal morphine presented a significantly lowest VAS on postoperative day 1 and 3 compared to patients performing intravenous morphine while in group B mean VAS was statistically significant lower only on the first day. The emergence of pruritus was significantly higher in patients performing intrathecal morphine. The day of complete canalization was different in Group A patients in favor of intrathecal morphine as well as the length of stay. The present study showed that intrathecal morphine allows to achieve important management goals with minimal side effects and complications, in particular in case of laparoscopic hysterectomy.

Effects of 5 µg/kg intrathecal morphine for postoperative analgesia in pediatric patients undergoing major surgery.

The effects and analgesic adequacy of intrathecal morphine (ITM) administration have been studied less frequently than other regional analgesia techniques in pediatric surgical procedures. To evaluate the efficacy and adverse event rate of 5 µg/kg ITM administration for postoperative analgesia according to age group. We retrospectively evaluated the medical records of patients who underwent major pediatric surgery and were administered ITM for postoperative analgesia. Patients were divided into three age groups: ≤ 5years (group I), 5.1-13years (group II) and > 13years (group III). All patients received ITM 5 µg/kg (max 300 μg) through the L4-5 or L5-S1 interspace. Postoperative pain (modified pediatric objective pain score > 4), need for rescue analgesics, sleep interruption due to pain, sedation (Ramsay sedation scale score > 3), opioid-related postoperative adverse events (at 0, 4, 8, 12, and 24 h after intervention), hemodynamic data and nurse satisfaction with the analgesic method were compared between groups. The analysis included 100children (47girls, 9 ± 5.4years). Groups were similar regarding postoperative rescue analgesia consumption and sleep interruption (p = 0.238, p = 0.958), 96% of the children did not require rescue analgesia, and sleep interruption was not observed in 97%. Postoperative adverse events were pruritus in 14 and nausea/vomiting in 9 patients (p = 0.052). Overall, nurses were satisfied or very satisfied in 99% of the cases. Administration of 5 µg/kg ITM can be used for postoperative analgesia in pediatric surgery in all age groups, with no severe adverse events and high nurse satisfaction with analgesic management.

P.118 Postoperative monitoring following neuraxial opioid administration for caesarean sections across maternity units in the Republic of Ireland: A national survey

Introduction: Neuraxial opioids are a well-recognised, effective means of providing post-operative analgesia following caesarean section (CS). Hydrophilic opioids e.g. morphine, can yield prolonged analgesia post-CS. Although rare in the obstetric population, delayed respiratory depression is a serious risk following neuraxial opioid use. The ASA Closed Claim database reports 16 cases of respiratory depression in first 24 h between 2001 and 2007 involving neuraxial opioid use, resulting in death or permanent brain damage in the majority of patients. [1] Weinger M. Dangers of postoperative opioids. APSF Newsletter 2007;21:61–8. Google Scholar Following intrathecal morphine administration for CS, hourly observations are advised in the first 12 h by the ASA Practice Guidelines. [2] American Society of Anesthesiologists Task Force on Neuraxial Opioids. Practice guidelines for the prevention, detection, and management of respiratory depression associated with neuraxial opioid administration. Anesthesiology 2016;124:535-52. Google Scholar The NICE clinical guideline advises hourly observations for the first 24 h. [3] NICE. Caesarean section Clinical guideline [CG132] 2011. https://www.nice.org.uk/guidance/cg132. Google Scholar The AAGBI Guidelines for Obstetric Anaesthetic Services do not advise a specific frequency for monitoring in this patient cohort. No standardised national policy exists across Irish Maternity Units for monitoring post neuraxial opioid administration. We have conducted a national survey of all units regarding monitoring policies following neuraxial opioid administration for CS.

The Effect of Intravenous Dexamethasone on Postoperative Nausea and Vomiting After Cesarean Delivery With Intrathecal Morphine: A Randomized-controlled Trial

(Can J Anesth. 2020;67:817–826) For women having a cesarean delivery, the estimated incidence of postoperative nausea and vomiting (PONV) ranges from 30% to 80%. Compared with spinal anesthesia without intrathecal opioid, the administration of intrathecal morphine has been associated with an increase in PONV, by up to 5-fold. According to one meta-analysis, the administration of intravenous (IV) dexamethasone showed a significant reduction in PONV in patients receiving epidural morphine – but not among those receiving intrathecal morphine. In the meta-analysis, 6 randomized-controlled trials (RCTs) studied the use of IV dexamethasone prior to epidural morphine and 2 RCTs studied its use prior to the end of surgery but not before intrathecal morphine administration. Whether the timing of IV dexamethasone is important for prophylaxis of PONV remains unclear. The aim of this study was to determine whether intravenous dexamethasone reduces the incidence of PONV when administered prior to intrathecal morphine during spinal anesthesia.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

The safety and efficacy of intrathecal morphine in pediatric spinal deformity surgery: a 25-year single-center experience.

Pre-incision intrathecal morphine (IM) is a popular adjunct in adolescent idiopathic spinal deformity surgery. This study represents our 25-year experience with IM in all diagnostic groups undergoing posterior spinal fusion (PSF) and segmental instrumentation (SI). Our prospective Pediatric Orthopaedic Spine Database (1992-2018) identified all patients undergoing PSF and SI. We included patients 21years of age or less, had a PSF with SSI, and received the recommended IM dose of 9-19 mcg/kg (up to 1mg) or no IM. We assessed demographics, pain scores, duration of surgery, time to first dose of narcotics, pediatric intensive care unit (PICU) admission, length of hospital stay, and IM complications (respiratory depression, pruritus, nausea/vomiting). There were 984 patients who met inclusion criteria: 760 patients received IM, 224 did not (non-IM).They were divided into 5 diagnostic groups: idiopathic, neuromuscular, syndromic, and congenital scoliosis and kyphosis. The mean first post-operativeopioid following IM administration was at 16.1h in the IM group compared to 8.7h in the non-IM group (p = < 0.001). The post-operative pain scores in the IM groups were significantly lower (p = < 0.001). Sixteen patients (2%) in the IM group were admitted to the PICU for observationsecondary to respiratory depression, none requiring re-intubation. There were no other complications related to IM. Pre-incision IM is a safe adjunct for pain management in select children in all diagnostic groups undergoing spinal deformity surgery. There were no serious complications. III.

Isobolographic analysis reveals antinociceptive synergism between Phα1β recombinant toxin and morphine in a model of cancer pain in C57BL/6J mice.

Background:Phoneutria nigriventer venom contains Phα1β. This toxin and its recombinant form have a remarkable analgesic potential that is associated with blockage of voltage-gated calcium channels and TRPA1 receptors. Although morphine is a mainstay drug to treat moderate and severe pain related to cancer, it has serious and dose-limiting side effects. Combining recombinant Phα1β and morphine to treat pain is an interesting approach that has been gaining attention. Therefore, a quantitative and reliable method to establish the strength of the antinociceptive interaction between these two substances is necessary. The present study was designed to investigate the nature of the functional antinociceptive (analgesic) interaction between Phα1β recombinant toxin and morphine in a model of cancer pain.Methods:Melanoma was produced by intraplantar inoculation of B16-F10 cells into the right paw of C57BL/6J mice. Von Frey filaments measured the paw-withdrawal threshold after intrathecal administration of morphine, recombinant Phα1β, and their combination. Thermal hyperalgesia was assessed using Hargreaves apparatus. The degree of interaction was evaluated using isobolographic analysis. Spontaneous and forced motor performance was assessed with the open-field and rotarod tests, respectively.Results:Co-administration of recombinant Phα1β and morphine synergistically reverses the melanoma-induced mechanical hyperalgesia. The potency of the mixture, measured as the effective dose to reach 50% of maximum possible effect (MPE) in ameliorating mechanical hyperalgesia, was about twice fold higher than expected if the interaction between morphine and recombinant Phα1β was merely additive. Treatment with the combination at doses necessary to reach 50% of MPE caused no spontaneous nor forced motor alterations.Conclusion:The combinatorial use of recombinant Phα1β and morphine allows significant and effective dose reduction of both agents, which has translational potential for opioid-sparing approaches in pain management related to cancer.

267. The impact of preventative multimodal analgesia on postoperative opioid requirement and pain control in patients undergoing lumbar fusions

BACKGROUND CONTEXT Preventive multimodal analgesia (PMA) addresses multiple sources and pathways of acute and chronic pain by interfering with peripheral and central sensitization and should provide a way to achieve safer and more effective pain management with reduced opioid medication use. PURPOSE The main objectives of this study were to determine the impact of PMA on postoperative opioid requirements and analgesic effectiveness in patients undergoing lumbar fusion surgery. STUDY DESIGN/SETTING A prospective observational study with a historical reference group was performed. PATIENT SAMPLE The study compared postoperative opioid requirement and analgesic effect in a total of 103 patients undergoing elective, one- or two-level transforaminal lumbar interbody fusion (TLIF) surgeries for symptomatic lumbar degenerative disc disease. The PMA patient group included 52 consecutive patients who received 1000 mg of acetaminophen, 300 – 900 mg of gabapentin, and 200 – 400 mg of celecoxib 1 hour before the procedure. The reference group included 51 patients who received 15 mg of morphine-equivalent dose (MED) preoperatively. OUTCOME MEASURES Postoperative opioid requirement and pain scores. METHODS Multiple linear regression was used to evaluate the influence of PMA on pain, MED and acetaminophen use over 4 postoperative days (PODs), while controlling for all variables likely to influence these outcomes, including age, gender, baseline opioid use, duration of surgery, postoperative intrathecal morphine use and administration of muscle relaxants and anticonvulsants. RESULTS The differences in opioid requirement and postoperative pain scores were statistically significant on all four postoperative days. The effect size varied from -0.54 to -0.99 for the postoperative opioid requirement and from -0.59 to -1.16 for postoperative pain indicating that these measures were reduced by about ½ to 1 standard deviation in the PMA patient group. CONCLUSIONS PMA is a highly effective method for postoperative pain management in patients undergoing lumbar fusion surgeries, which not only improves pain control, but also reduces opioid requirement. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Intrathecal Morphine Is Associated with Less Delirium Following Hip Fracture Surgery: A Register Study.

BackgroundDelirium is a common complication after proximal femoral fracture surgery, with pain and opioid consumption as the contributing factors. The administration of intrathecal morphine may decrease these factors postoperatively and potentially reduce delirium.ObjectivesThis research aimed to study the association between the use of intrathecal morphine and the occurrence of delirium.MethodsA retrospective analysis of a prospective register kept in a non-academic hospital in the Netherlands was performed. The register contained data of all patients with proximal femur fractures that were surgically treated with osteosynthesis or prosthesis. Patients receiving spinal anesthesia (SA group) were compared with patients receiving spinal anesthesia with the addition of intrathecal morphine (SIM group). The administration of either SA or SIM was based on the preference of the anesthesiologist. The primary outcome was the incidence of delirium, as defined by the DSM-V classification. The follow-up lasted until hospital discharge. Both univariate and multivariate analyses were performed.ResultsThe SA group consisted of 451 patients, and the SIM group included 34 patients. Delirium occurred in 19.7% in the SA group versus 5.9% in the SIM group (P = 0.046). This association remained significant after correction in multivariate analysis (OR of delirium in the SA group, 95% CI: 1.062 - 21.006, P = 0.041). Additionally, multivariate analysis revealed that age, gender, preoperative cognitive impairment, and fracture treatment (osteosynthesis or prosthesis) were independently associated with delirium.ConclusionsThis retrospective study found an independent association between the use of intrathecal morphine and a lower incidence of delirium. This clinically relevant decrease in delirium should be studied in a prospective randomized study.