Low-dose Morphine Research Articles

Low-Dose Morphine Does Not Cause Sleepiness in Chronic Obstructive Pulmonary Disease: A Secondary Analysis of a Randomized Clinical Trial.

Rationale: Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality, and daytime function have not been rigorously investigated. Objectives: We sought to determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. Methods: We conducted prespecified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained-release morphine versus placebo over 4 weeks commencing at 8 or 16 mg/d with blinded up-titration over 2 weeks to a maximum of 32 mg/d. Primary outcomes for these analyses were Week-1 Epworth Sleepiness Scale (ESS) and Karolinska Sleepiness Scale (KSS) scores on morphine versus placebo. Secondary outcomes included Leeds Sleep Evaluation Questionnaire scores (end of Weeks 1 and 4), KSS and ESS scores beyond Week 1, and associations between breathlessness, morphine, and questionnaire scores. Measurements and Main Results: One hundred fifty-six people were randomized. Week-1 sleepiness scores were not different on morphine versus placebo (ΔESS [95% confidence interval] versus placebo: 8-mg group, -0.59 [-1.99, 0.81], P = 0.41; 16-mg group, -0.72 [-2.33, 0.9], P = 0.38; ΔKSS vs. placebo, 8-mg group: 0.11 [-0.7, 0.9], P = 0.78; 16-mg group, -0.41 [-1.31, 0.49], P = 0.37). This neutral effect persisted at later time points. In addition, participants who reported reduced breathlessness with morphine at 4 weeks also showed improvement in LSEQ domain scores including perceived sleep quality and daytime function. Conclusions: Regular, low-dose morphine does not worsen sleepiness when used for breathlessness in COPD. Individual improvements in breathlessness with morphine may be related to improvements in sleep. Clinical trial registered with www.clinicaltrials.gov (NCT02720822).

Pronociceptive role of spinal Cav2.3 (R-type) calcium channels in a mouse model of postoperative pain.

More than 80% of patients may experience acute pain after a surgical procedure, and this is often refractory to pharmacological intervention. The identification of new targets to treat postoperative pain is necessary. There is an association of polymorphisms in the Cav2.3 gene with postoperative pain and opioid consumption. Our study aimed to identify Cav2.3 as a potential target to treat postoperative pain and to reduce opioid-related side effects. A plantar incision model was established in adult male and female C57BL/6 mice. Cav2.3 expression was detected by qPCR and suppressed by siRNA treatment. The antinociceptive efficacy and safety of a Cav2.3 blocker-alone or together with morphine-was also assessed after surgery. Paw incision in female and male mice caused acute nociception and increased Cav2.3 mRNA expression in the spinal cord but not in the incised tissue. Intrathecal treatment with siRNA against Cav2.3, but not with a scrambled siRNA, prevented the development of surgery-induced nociception in both male and female mice, with female mice experiencing long-lasting effects. High doses of i.t. SNX-482, a Cav2.3 channel blocker, or morphine injected alone, reversed postoperative nociception but also induced side effects. A combination of lower doses of morphine and SNX-482 mediated a long-lasting reversal of postsurgical pain in female and male mice. Our results demonstrate that Cav2.3 has a pronociceptive role in the induction of postoperative pain, indicating that it is a potential target for the development of therapeutic approaches for the treatment of postoperative pain.

A novel opioid/pramipexole combination treatment for the management of acute pain: a pilot study.

Despite their dangerous side effects, opioid drugs remain a standard of care for moderate to severe pain with few alternatives. Strategies to maintain the analgesic effects of opioids while minimizing the associated risks are needed. Pre-clinical studies have shown using a dopamine 3 receptor (D3R) agonist as an adjuvant to morphine provides superior analgesia against painful stimuli compared to morphine alone. Our objective was to test if adjunct treatment with a D3R agonist can lead to a reduction in opioid use while maintaining effective analgesia. This study was set up as a double-blinded, placebo-controlled randomized trial. Enrollment included acute renal colic patients presenting to the emergency department, from which patients were randomized to either the "control" or "study arm". The control group received standard treatment of care (morphine, 0.1 mg/kg; i.v.) and an oral placebo pill. The experimental group received half-dosed morphine and oral pramipexole pill (0.25 mg). Pain measurements including a numerical pain scale and visual analog scale were collected from enrollees at baseline and every subsequent 15 min. A total of 19 patients completed the study, 10 in the experimental arm and 9 in the control arm. During the study period, effective analgesia (50% decrease from baseline) was achieved in 80% of patients in the experimental arm vs. 33.3% in the control arm. Our pilot clinical trial demonstrated that D3R recruitment can serve as an effective adjuvant to low-dose morphine for control of renal colic pain and potentially other acute pain conditions. ClinicalTrials.gov, identifier, (NCT04160520).

Low-Dose Opioid Spinal Analgesia during Cesarean Section at the Commune 1 Reference Health Center of Bamako

The need to provide maternal comfort and facilitate rapid recovery during caesarean section requires pain management. The aim of our study of low-dose morphine spinal analgesia during caesarean section was to evaluate its effectiveness during and after the operation. Methodology: We conducted a prospective, descriptive, cross-sectional study lasting 6 months from 1 July to 31 December 2023. It involved 101 Caesarean women undergoing spinal analgesia, selected by random sampling at the reference health centre in Commune I of the Bamako district. Results: The mean age of the patients was 27 ±1.51 years, with ASA I classification in 63.4%. The combination of bupivacaine 10 mg and morphine 0.1 mg was used in 68.3% of cases. The mean duration of motor block release was 2.78 ± 0.7 hours. The manifestation of pain (VAS=0) was 100% at H1 (first hour), with peaks of VAS [1,3] in 42.57% and VAS [4,6] in 6.97% at H4 (fourth hour). Arterial hypotension was found in 57% of cases. From H12 onwards, all the women were very satisfied. Conclusion: The efficacy of morphine spinal analgesia during caesarean section has been proven in all our parturients from H12 (twelfth hour). However, pain management in the first few hours must be started with a well-adapted protocol.

Impact of chronic opioid on cognitive function and spermatogenesis in rat: An experimental study.

Opioid analgesics like morphine and methadone are widely used for managing severe pain; however, concerns over their potential misuse and adverse effects on the brain and reproductive system are significant. We aimed to investigate their impacts on spermatogenesis and cognitive function in male Norway rats. In this experimental study, 36 male Norway rats (250-300 gr, 6 months old) were divided into 6 groups: low-dose morphine, high-dose morphine, low-dose methadone, high-dose methadone, positive control (received normal saline at 5 mg/kg), and negative control (received no treatment). Morphine and methadone were administered intraperitoneally over 30 days at doses of 3 mg/kg and 7 mg/kg, respectively. Behavioral assessments evaluated anxiety, stress, and short- and long-term memory. Sperm parameters (viability, motility, morphology), hormonal analysis (testosterone, luteinizing hormone, follicle-stimulating hormone, estradiol), and gene expressions (Tp53, CatSper1) were assessed. A significant reduction in rat weight was observed in the high-dose morphine group (p = 0.0045), while testicular weights remained unchanged. Sperm abnormalities were observed with high doses of methadone and morphine. High-dose methadone significantly reduced offspring count (p = 0.0004). Levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol varied significantly across treatment groups. Gene expression was altered in response to treatments (p 0.05). Prolonged exposure to methadone and morphine resulted in memory dysfunction, chronic stress, hormonal disturbances, altered gene expression, and fertility complications. These effects were more pronounced at higher doses, highlighting the importance of careful dosage management in opioid therapy.

Long-term intrathecal infusion of low-dose morphine effectively relieves symptoms of severe restless legs syndrome/Willis-Ekbom disease without inducing opioid tolerance.

Restless legs syndrome/Willis-Ekbom disease (RLS/WED) causes a strong urge to move legs while resting. Restless legs syndrome/WED is an often-inherited disease occurring in 3% to 10% of adult populations, increasing with age. Severity varies from mild disturbance of sleep to painful restless legs and arms, loss of sleep, fatigue, and risk of suicide. Dopaminergic drugs relieve symptoms, but cause augmentation, ie, initially helpful but later increase the burden of symptoms. Oral gabapentinoids and opioids are often added, but opioid tolerance and adverse effects are common. With the high prevalence and incomplete help from oral drugs, significant unmet needs exist for effective therapy for severe RLS/WED. Ongoing spinal intrathecal infusion of low-dose morphine is effective, but not generally recognized, as only 12 cases have been published since 2002. We report 7 patients suffering from severe RLS/WED, who had no relief from oral dopaminergic, gabapentinoid, or opioid drugs; they all had excellent relief during ongoing spinal intrathecal infusion of morphine at only 1 to 5 μg/h, ongoing for 1 to 21 years without need of higher doses of morphine.. We suggest that morphine may be transported with the cerebrospinal fluid reaching and readjusting malfunctioning dopamine neuronal systems in the brain and spinal cord. The effects last only as long as the infusion continues. A patient with RLS/WED and persistent genital arousal disorder (PGAD) was relieved of both RLS/WED and PGAD symptoms. These case reports suggest that intrathecal infusion of low-dose morphine is an effective treatment of severe RLS.

Low dose of morphine to relieve dyspnea in acute respiratory failure: the OpiDys double-blind randomized controlled trial

BackgroundMorphine relieves dyspnea in various clinical circumstances. Whether or not this applies to patients admitted to intensive care units (ICUs) for acute respiratory failure (ARF) is unknown. We evaluated the efficacy and safety of low-dose morphine on dyspnea in patients admitted to the ICU for ARF.MethodsIn this single-center, double-blind, phase 2, randomized, controlled trial, we assigned non-intubated adults admitted to the ICU for ARF with severe dyspnea, defined by a visual analog scale for dyspnea (dyspnea-VAS) from zero (no dyspnea) to 100 mm (worst imaginable dyspnea) ≥40 mm, to receive a low dose of Morphine Hydrochloride (intravenous titration followed by subcutaneous relay) or Placebo. All patients received standard therapy, including etiological treatment and non-invasive respiratory support.ResultsTwenty-two patients were randomized, 11 in each group. The average dyspnea (median [interquartile range]) over 24 hours did not significantly differ between the two groups (40 [25 – 43] mm in the Morphine group vs. 40 [36 – 49] mm in the Placebo group, p=0.411). Dyspnea-VAS was lower in the Morphine group than in the Placebo group at the end of intravenous titration (30 [11 – 30] vs. 35 [30 – 44], p=0.044) and four hours later (18 [10 – 29] vs. 50 [30 – 60], p=0.043). The cumulative probability of intubation was higher in the Morphine group than in the Placebo group (p=0.046)ConclusionIn this phase 2 pilot trial, morphine did not improve 24-hour average dyspnea in adult patients with ARF, even though it had a statistically significant immediate effect. Of concern, Morphine use was associated with a higher intubation rate.Trial registrationThe protocol was declared on the ClinicalTrial.gov database (no. NCT04358133) and was published in September 2022.

Chronic breathlessness in fibrotic interstitial lung diseases-patient centered assessment and management in outpatient settings.

Chronic breathlessness (CB) or dyspnea is prevalent in fibrotic interstitial lung diseases (F-ILD). It is the main driver of a poor health-related quality of life (HRQOL). Timely and accurate assessment and management of CB are paramount in F-ILD care. This is reflected in latest American and European guidelines that recommend early integration of symptom-targeted therapies. Despite calls for improved CB care, evidence indicates that it remains under recognized and under treated. This narrative review focuses on the current evidence for CB assessment and management in F-ILD and proposes an algorithm for patient-centered management of CB in an outpatient setting. An overview of CB assessment tools is provided along with recommendations from guidelines and experts. The limited evidence base for CB interventions in ILD is reviewed; existing dyspnea guidelines recommend a hierarchical approach to therapies starting with the implementation of nonpharmacologic interventions (NPI). Pulmonary rehabilitation is the most common NPI in F-ILD, that improves function, dyspnea, and HRQOL. Oxygen can be prescribed to treat CB associated with exertional hypoxemia early in the course of F-ILD, with evidence suggesting short-term improvements in CB and HRQOL. For patients with severe, persistent CB despite optimization of NPI and oxygen, opioids can be prescribed, initially as short-acting, low-dose oral morphine with prophylactic doses for exertion and as needed for crises. Self-management education and written action plans may help improve patient confidence and control. Development of competency in symptom management and fostering a professional and institutional culture prioritizing CB will advance patient care and should be a priority for F-ILD patients.

Effectiveness of Intravenous Low-Dose Ketamine Versus Morphine for Procedural Burn Pain Management During Dressing Changes: A Randomized Clinical Trial

Background: There is limited literature on using low-dose intravenous ketamine as a single agent for procedural burn pain management during adult dressing changes. Aims & Objectives: To determine the effectiveness of low-dose ketamine compared to morphine as a single analgesic agent in procedural burn pain management during dressing changes. Materials & Methods: We performed an institutional review board-approved, randomized, prospective, double-blinded, controlled, non-inferiority trial. All adult patients 18 years and above scheduled for dressing change were screened. Patients who consented were randomized to receive low-dose ketamine infusion at 0.2mg/kg/hr. In the treatment group, morphine infusion at 0.1mg/kg/hr. In the control group. The primary endpoint was pain intensity, measured using a visual analog scale. Data were analyzed on an intention-to-treat (ITT) approach. Secondary endpoints included rescue analgesia requirements and the occurrence of adverse effects in both groups. Results: 82 patients were enrolled (ketamine 41 vs. morphine 41). We compared VAS scores at 5-minute intervals during the dressing changes. Overall, pain scores are similar in both groups (p-value=0.595). The pain control was homogenous. However, the morphine group required more rescue analgesia throughout the dressing changes than the low-dose ketamine group (p=0.013 at T15, p<0.001 at T20, and p<0.001 at T30). The occurrence of side effects was similar in both groups. Conclusion: This study suggests that low-dose ketamine provides as effective and more predictable procedural analgesia as morphine during dressing procedures for adult burn patients.

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

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.

Intrathecal morphine delivery at prepontine cistern to control refractory cancer-related pain: a case report of extensive metastatic and refractory cancer pain

BackgroundExtensive metastatic and refractory cancer pain is common, and exhibits a dissatisfactory response to the conventional intrathecal infusion of opioid analgesics.Case PresentationThe present study reports a case of an extensive metastatic esophageal cancer patient with severe intractable pain, who underwent translumbar subarachnoid puncture with intrathecal catheterization to the prepontine cistern. After continuous infusion of low-dose morphine, the pain was well-controlled with a decrease in the numeric rating scale (NRS) of pain score from 9 to 0, and the few adverse reactions to the treatment disappeared at a low dose of morphine.ConclusionsThe patient achieved a good quality of life during the one-month follow-up period.

The effects of low-dose morphine on sleep and breathlessness in chronic obstructive pulmonary disease: a randomised controlled trial

The effects of low-dose morphine on sleep and breathlessness in chronic obstructive pulmonary disease: a randomised controlled trial

Individual Factors Modifying Postoperative Pain Management in Elective Total Hip and Total Knee Replacement Surgery.

Total hip and knee replacements are the most common orthopedic procedures performed due to osteoarthritis. Pain is an intrinsic symptom accompanying osteoarthritis, persisting long before surgery, and continuing during the preoperative and postoperative periods. Appropriate pain management after surgery determines the comfort, duration, and cost of hospitalization, as well as the effectiveness of postoperative rehabilitation. Individual differences in pain perception and tolerance in orthopedic patients remain an important research topic. Therefore, the aim of this study was to investigate the predictors of analgesic requirements (morphine, acetaminophen, and ketoprofen), including individual pain threshold and tolerance, body mass index (BMI), diabetes, and beliefs about pain control in patients undergoing elective hip or knee arthroplasty using a multilevel regression model (N = 147, 85 women, 62 men, 107 after hip replacement, and 40 after knee replacement). Results: Higher pain tolerance was associated with a lower dose of morphine per kg after surgery. Patients undergoing hip surgery received a lower dose of ketoprofen than patients undergoing knee surgery. The more the patient believed in personal pain control, the stronger the negative relationship between pain tolerance and morphine requirement. The lowest doses were given to patients with the highest pain tolerance and the greatest belief in personal control. Factors such as belief in pain control and pain tolerance should be considered in comprehensive postoperative pain management in orthopedic patients to reduce opioid doses and, thus, side effects.

Sensitization of human and rat nociceptors by low dose morphine is toll-like receptor 4-dependent.

While opioids remain amongst the most effective treatments for moderate-to-severe pain, their substantial side effect profile remains a major limitation to broader clinical use. One such side effect is opioid-induced hyperalgesia (OIH), which includes a transition from opioid-induced analgesia to pain enhancement. Evidence in rodents supports the suggestion that OIH may be produced by the action of opioids at Toll-like Receptor 4 (TLR4) either on immune cells that, in turn, produce pronociceptive mediators to act on nociceptors, or by a direct action at nociceptor TLR4. And, sub-analgesic doses of several opioids have been shown to induce hyperalgesia in rodents by their action as TLR4 agonists. In the present in vitro patch-clamp electrophysiology experiments, we demonstrate that low dose morphine directly sensitizes human as well as rodent dorsal root ganglion (DRG) neurons, an effect of this opioid analgesic that is antagonized by LPS-RS Ultrapure, a selective TLR4 antagonist. We found that low concentration (100nM) of morphine reduced rheobase in human (by 36%) and rat (by 26%) putative C-type nociceptors, an effect of morphine that was markedly attenuated by preincubation with LPS-RS Ultrapure. Our findings support the suggestion that in humans, as in rodents, OIH is mediated by the direct action of opioids at TLR4 on nociceptors.

“Low-dose ketamine versus morphine in the treatment of acute pain in the emergency department: A meta-analysis of 15” randomized controlled trials

ObjectiveTo compare the effectiveness and safety of ketamine and morphine in adult patients with acute pain in emergency department (ED) by using a meta-analysis method. MethodsThis study was based on the Cochrane methodology for conducting a meta-analysis. Only randomized controlled trials (RCTs) were eligible for this study, with an experimental group that received low-dose ketamine and a control group that received morphine. The participants were adults who had acute pain in the ED. The primary outcome measures were the numeric rating scale (NRS) and visual analog scale (VAS). The secondary outcome measures were the complete resolution of pain, NRS reduction ≥3 points, NRS reduction ≥50% or 60%, change of NRS score, change of VAS score, rescue analgesia, satisfaction and adverse events. Subgroup analysis was performed for studies with intravenous and intranasal administration of ketamine. The Review Manager Database was used to analyze the included studies. Results15 RCTs involving 1768 patients were included. The ketamine group had lower NRS scores than morphine group at 30 min (MD, −0.77 [95% CI, −0.93 to −0.61]; p < 0.00001), while the morphine had better analgesic effects at 120 min after treatment (MD, 0.33 [95% CI, 0.15 to 051]; p = 0.0003). The subjects of complete resolution of pain in the ketamine group performed better than those in the morphine group at 15 min (RR 3.18, 95% CI 1.75 to 5.78; p = 0.0001). Compared with the morphine group, the ketamine group had a lower incidence of adverse events requiring intervention (RR, 0.34 [95% CI, 0.18 to 0.66]; p = 0.001). Subgroup analysis of intravenous ketamine showed that ketamine had lower VAS score than the morphine group at 30 min. However, also on the 30-min VAS score, intranasal ketamine analgesia was less effective than morphine. ConclusionsKetamine had better analgesic effects in the early stages after treatment, while morphine maintained more durable effects. Compared with morphine, ketamine had a lower incidence of adverse events requiring intervention. The results of subgroup analysis showed that intravenous administration of ketamine was more effective than intranasal administration.

Comparison of intrathecal low-dose bupivacaine and morphine with intravenous patient control analgesia for postoperative analgesia for video-assisted thoracoscopic surgery

BackgroundThoracoscopic surgical techniques continue to advance, yet the intensity of postoperative pain remains significant, impeding swift patient recovery. This study aimed to evaluate the differences in postoperative pain and recuperation between patients receiving intrathecal morphine paired with low-dose bupivacaine and those administered general anesthesia exclusively.MethodsThis randomized controlled trial enrolled 100 patients, who were allocated into three groups: Group M (5 μg/kg morphine intrathecal injection), Group B (5 μg/kg morphine combined with bupivacaine 3 mg intrathecal injection) and Group C (intrathecal sham injection). The primary outcome was the assessment of pain relief using the Numeric Rating Scale (NRS). Additionally, intraoperative remifentanil consumption was quantified at the end of the surgery, and postoperative opioid use was determined by the number of patient-controlled analgesia (PCIA) compressions at 48 h post-surgery. Both the efficacy of the treatments and any complications were meticulously recorded.ResultsPostoperative NRS scores for both rest and exercise at 6, 12, 24, and 48 h were significantly lower in groups M and B than in group C (P<0.05). The intraoperative remifentanil dosage was significantly greater in groups M and C than in group B (P<0.05), while there was no significant difference between groups M and C (P>0.05). There was no significant difference in intraoperative propofol dosage across all three groups (P>0.05). Postoperative dosages of both sufentanil and Nonsteroidal anti‐inflammatory drugs (NSAIDs) were significantly less in groups M and B compared to group C (P<0.05). The time of first analgesic request was later in both groups M and B than in group C (P<0.05). Specific and total scores were elevated at 2 days postoperative when compared to scores at 1 day for all groups (P<0.05). Furthermore, at 1 day and 2 days postoperatively, both specific scores and total scores were higher in groups M and B compared to group C (P<0.05).ConclusionIntrathecal administration of morphine combined with bupivacaine has been shown to effectively ameliorate acute pain in patients undergoing thoracoscopic surgery.Trial registrationThe trial was registered on ClinicalTrials.gov: ChiCTR2200058544, registered 10/04/2022.

Evaluation and management of chronic cough in adults

Background: Chronic cough (CC), a cough that lasts &gt; 8 weeks, has an overall prevalence of 5‐11% in adults, peaking between 60 and 80 years of age. Of the 15% of patients who remain undiagnosed or refractory to treatment, two thirds are women. Objective: The objective was to present an updated evidence-based algorithmic approach for evaluating and managing CC, with emphasis on treatment modalities for refractory CC. Methods: A literature search was conducted of medical literature data bases for guidelines, position papers, systematic reviews, and clinical trials from January 2022 to June 2023, on the evaluation and management of CC. Results: The initial assessment should be limited to a detailed history, physical examination, chest radiograph, spirometry, exhaled nitric oxide, blood eosinophil count, and measurement of cough severity and quality of life by using validated instruments. The top diagnoses to consider are asthma, chronic obstructive pulmonary disease, nonasthmatic eosinophilic bronchitis, gastroesophageal reflux disease, and upper airway cough syndrome. Additional studies are only obtained when red flags are present or the patient fails to respond after avoidance of high-risk factors, e.g., smoking and angiotensin-converting enzyme inhibitors, and 4‐6 weeks of empiric treatment for the most likely respiratory and gastrointestinal diseases. When diagnostic tests and/or specific directed treatments fail to control CC, low-dose morphine (preferred), gabapentin, pregabalin, and/or cough control therapy are recommended. Non-narcotic purinergic 2×3 (P2×3) receptor antagonists, gafapixant and campilixant, are currently being studied for CC. Conclusion: For the evaluation and management of patients with CC, clinicians should use an algorithmic approach and identify “red flags,” reduce high-risk factors, and use empiric treatment for the five top diagnoses before extensive diagnostic testing. Current treatment for refractory cough is limited to symptomatic management.

The reinstatement of the expression phase of morphine-induced conditioned place preference in male Wistar rats under ventral tegmental area stimulation and brief inactivation.

Previous research has found that the electrical stimulation of the ventral tegmental area (VTA) is involved in drug-dependent behaviors and plays a role in reward-seeking. However, the mechanisms remain unknown, especially the effect of electrical stimulation on this area. Therefore, this study aimed to investigate how the electrical stimulation and the temporary inactivation of VTA affect the morphine- dependent behavior in male rats. The adult Wistar male rats were anesthetized with ketamine and xylazine. The stimulation electrode (unilaterally) and the microinjection cannula (bilaterally) were implanted into the VTA, stereotaxically. Then, the rats underwent three-day of repeated conditioning with subcutaneous morphine (0.5 or 5 mg/kg) injections, in the conditioned place preference apparatus, followed by four-day forced abstinence, which altered their conditioning response to a morphine (0.5 mg/kg) priming dose on the ninth day. On that day, rats were given high- or low-intensity electrical stimulation or reversible inactivation with lidocaine (0.5 pL/site) in the VTA. Results showed that the electrical stimulation of the VTA with the high intensity (150 μA/rat), had a minimal effect on the expression of morphine-induced place conditioning in rats treated with a high dose (5 mg/kg) of morphine. However, the reversible inactivation of the VTA with lidocaine greatly increased place preference in rats treated with a low dose (0.5 mg/kg) of morphine. Additionally, the reinstatement of 0.5 mg/kg morphine-treated rats was observed after lidocaine infusion into the VTA. These results suggest that VTA electrical stimulation suppresses neuronal activation, but the priming dose causes reinstatement. The VTA may be a potential target for deep brain stimulation-based treatment of intractable disorders induced by substance abuse.

The Effect of Preoperative, Low-Dose Intrathecal Morphine on Patient Outcomes Following Lumbar Fusion Surgery: Can We Teach an Old Dog New Tricks?

Early pain control after lumbar fusion presents a challenge to patients and providers. Intrathecal morphine (ITM) has been used at the end of these procedures with limited benefit, but recent data suggest low-dose ITM at case initiation may be effective. This study aims to evaluate the use of preoperative ITM during lumbar fusion to determine whether there is a benefit for these patients. One hundred and eighty lumbar fusion patients between 1 January 2018 and 31 May 2022 were evaluated. Patients were grouped by whether they received preoperative, low-dose ITM or not. Outcomes of interest included hospital narcotic consumption, pain scores, opioid-related complications, and complications within the first 90 days. Sixty-five study patients received 200 µg ITM at case initiation and 115 did not. No differences in length of stay, discharge disposition, or complications in the first 90 days were noted. ITM patients received fewer milligram morphine equivalents in the postanesthesia care unit (9.7 ± 31.23 vs 21.83 ± 21.07; P = 0.006) and on postoperative day 0 (18.60 ± 35.47 vs 35.47 ± 28.51; P = 0.001). Pain scores were lower in the ITM group both in the postanesthesia care unit and on postoperative day 0, with a decrease in extreme pain scores (>7; 35.4% vs 53.0%; P = 0.034). ITM appears to be safe and effective for reducing early pain and narcotic consumption on the day of surgery for lumbar fusion patients and may hold value for incorporation into rapid recovery protocols and for improving pain-related patient satisfaction. ITM appears to be safe and effective for reducing early pain and narcotic consumption on the day of surgery for lumbar fusion patients and may hold value for incorporation into rapid recovery protocols and for improving pain-related patient satisfaction.

Implementation of Early Recovery After Caesarean Surgery Protocol in Floating Hospital (Case Series)

Introduction: Enhanced Recovery After Caesarean Surgery (ERACS) is a new concept that combines various evidence-based perioperative care to reduce post-operative complications and accelerate patient recovery after Caesarean Surgery (C-Section). The advantages of the ERACS Protocol, including accelerating patients' recoveries, shortening hospital stays, and reducing post-operative complications, make it suitable to be applied in floating hospitals. The problem is whether this protocol can be applied if it is carried out in a floating hospital with all its limitations. We would like to present our case series with modified ERACS protocol in Floating Hospital Ksatria Airlangga. Case Presentation: We present 4 patients scheduled for elective C-Section. Neuraxial opioids with low-dose morphine, the most frequently used technique in ERACS, were not administered due to its unavailability in Ksatria Airlangga Floating Hospital. We provide pre-emptive analgesia and multimodal analgesia to obtain adequate perioperative analgesia. All patients were admitted to the nearest public health centre for post-operative observation and discharged after 1 to 2 days. Satisfaction was achieved in all patients without any significant postoperative complications. Conclusion: The ERACS protocols’ main goal can be achieved even under limited conditions, but several adjustments are required according to the available resources.