Low-dose Morphine Research Articles

Sodium chloride injection to treat opioid overdose; Does it work? A preclinical study

Opioid overdoses (ODs) are increasing in Mexico's northern border. Because naloxone is usually not available, witnesses inject common salt (NaCl) into a vein of OD victims in an attempt to help them regain consciousness. Despite this widespread practice, no preclinical studies have addressed the efficacy of NaCl as an opioid antidote. Here we tested saline solutions at different concentrations. Because the highest (31.6 %) caused tail necrosis, we selected 17.7 % as a hypertonic saline solution (HSS) to determine if it could prevent the lethal effect of morphine (Mor), fentanyl (Fen), or Mor + Fen in adult Wistar male rats. We also evaluated if NaCl could modify the opioid antagonist effect of naloxone. Our results show that HSS: a) sensitizes animals to thermal but not mechanical stimuli; b) does not prevent mortality caused by high morphine or fentanyl doses; c) decreases the latency to recovery from the sedative effects caused by low doses of morphine or fentanyl; and d) increases naloxone's efficacy to prevent the lethality produced by Mor or Fen, but not by Mor + Fen. These results suggest that HSS is marginally effective in shortening the recovery time from nonfatal opioid ODs and increases naloxone's efficacy to counteract opioid-induced ODs.

Involvement of T-type calcium channels in the mechanism of low dose morphine-induced hyperalgesia in adult male rats

It has been shown that systemic and local administration of ultra-low dose morphine induced a hyperalgesic response via mu-opioid receptors. However, its exact mechanism(s) has not fully been clarified. It is documented that mu-opioid receptors functionally couple to T-type voltage dependent Ca+2 channels. Here, we investigated the role of T-type calcium channels, amiloride and mibefradil, on the induction of low-dose morphine hyperalgesia in male Wistar rats. The data showed that morphine (0.01 μg i.t. and 1 μg/kg i.p.) could elicit hyperalgesia as assessed by the tail-flick test. Administration of amiloride (5 and 10 μg i.t.) and mibefradil (2.5 and 5 μg i.t.) completely blocked low-dose morphine-induced hyperalgesia in spinal dorsal horn. Amiloride at doses of 1 and 5 mg/kg (i.p.) and mibefradil (9 mg/kg ip) 10 min before morphine (1 μg/kg i.p.) inhibited morphine-induced hyperalgesia. Our results indicate a role for T-type calcium channels in low dose morphine-induced hyperalgesia in rats.

European Respiratory Society guidelines on the diagnosis and treatment of chronic cough in adults and children

These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.

Gabapentin enhances the antinociceptive effect of intrathecal morphine in refractory cancer pain patients.

Morphine infusion through Intrathecal Drug Delivery System (IDDS) is widely used to relieve refractory cancer pain. However, continuous escalation of morphine dose caused by opioid tolerance and/or progress of cancer was commonly observed. Combining morphine with medications of different analgesic mechanisms is applied to blunt the rate of morphine increase. The purpose of this study was to determine the analgesic efficacy and safety of combining gabapentin with morphine after IDDS implantation. This study compared patients that received IDDS implantation from January 1, 2017 to November 10, 2018 in our institute. Key outcomes included change in mean pain score, dose of morphine used in patients, percentage of patients with 30% and 50% reduction in mean pain score, Patient Global Impression of Change scores, breakthrough pain characters and side effects. 34 patients in the combination group (morphine + gabapentin) and 40 patients in the monotherapy group(morphine)were analyzed. The results showed that both therapy groups achieved similar analgesic efficacy, demonstrated by Numerical rating scale (2.42 ± 0.88 vs 2.57 ± 0.85; Combination vs Monotherapy), PGIC and responder status. Mean daily dose of morphine was significantly lower in combination group compared to monotherapy group (3.54 ± 1.29mg vs 4.64 ± 1.28mg, P = 0.007). More patients experienced dizziness and somnolence after receiving combination therapy compared to morphine-alone treatment although no statistical significance was found (P = 0.49). Addition of gabapentin achieved similar analgesic efficacy with lower dose of morphine compared to morphine alone accompanying with higher incidence of dizziness and somnolence.

Neuraxial Morphine for Postoperative Analgesia after Caesarean Deliveries

The use of neuraxial morphine, in combination with nonopioid analgesic regimens for postoperative analgesia after Caesarean deliveries is common practice, especially in the Anglo-American world. Neuraxial morphine offers a longer-lasting superior analgesia than intravenous opioids or patient-controlled analgesia. If neuraxial anaesthesia is being used for a caesarean delivery, it may be recommended to concomitantly administer neuraxial morphine for the postoperative analgesia.A low dose of neuraxial morphine in a healthy parturient bears a low morbidity and mortality risk. The optimal frequency, duration and modality of respiratory monitoring for patients at low risk for respiratory depression is dependent on the dose of morphine administered and the patient-specific and obstetric risk profile.

Evaluation of analgesic interaction between morphine, maropitant and dexmedetomidine in dogs undergoing ovariohysterectomy

ABSTRACT Aims To compare the analgesic effect of morphine combined with maropitant and/or dexmedetomidine to morphine alone but at a higher dose, and to evaluate the pharmacokinetics of the drug combinations, in dogs undergoing ovariohysterectomy (OHE). Methods Forty client-owned dogs were randomised into four treatment groups (n = 10 per group) each to receive a different analgesic protocol. After premedication with I/M acepromazine, anaesthesia was induced with propofol to effect and maintained with isoflurane in 100% oxygen delivered via a circle system. The heart rate, respiratory rate, blood pressure, haemoglobin oxygen saturation, end-tidal partial pressure of carbon dioxide, electrocardiogram and rectal temperature were monitored during anaesthesia. The test drugs (Mor: 0.6 mg/kg morphine; Maro + Mor: 0.3 mg/kg morphine and 1 mg/kg maropitant; Dex + Mor: 0.3 mg/kg morphine and 10 μg/kg dexmedetomidine; Dex + Maro + Mor: 0.2 mg/kg morphine, 7 μg/kg dexmedetomidine and 0.7 mg/kg maropitant) were administered I/M after induction of anaesthesia and 30 minutes before the expected start time of ovariohysterectomy, which was carried out by veterinary students under veterinary supervision. The short form of the Glasgow composite measure pain scale (CMPS-SF) and visual analogue scale (VAS) were used for pain assessment at 15 and 30 minutes and 1, 2, 3, 6, 9 and 24 hours after extubation. Dogs with CMPS-SF pain score ≥ 6 received rescue analgesia with S/C buprenorphine (0.02 mg/kg). Blood samples were collected before, 15, 30, 60 and 120 minutes after injection of the test drugs and concentration of the test drugs in plasma was determined by liquid chromatography-mass spectrometry. Results Dogs that received Dex + Mor had significantly lower CMPS-SF (estimate of difference = –1.53 (SE 0.58); p = 0.010) and VAS (estimate of difference = –0.67 (SE 0.25); p = 0.007) scores compared to the dogs that received morphine alone. There was no evidence of a difference in the number of dogs requiring rescue between groups. All dogs that received dexmedetomidine showed cardiac arrhythmia and second-degree heart block. Mean (SD) maximum concentrations (Cmax, ) of morphine in plasma were 6.8 (4.56), 9.56 (8.29), 9.30 (3.35) and 18.99 (9.41) ng/mL for the groups Dex + Mor, Dex + Maro + Mor, Maro + Mor and Mor respectively. The Cmax of morphine was significantly lower in the Dex + Mor (p = 0.004), Dex + Maro + Mor (p = 0.034) and Maro + Mor (p = 0.018) groups compared to the Mor group. Conclusions For dogs undergoing ovariohysterectomy, lower doses of morphine (0.2 and 0.3 mg/kg) combined with dexmedetomidine or maropitant may provide analgesia equivalent to or better than morphine when given alone at a higher dose (0.6 mg/kg). Abbreviations: AUC: Area under curve; Cmax: Maximum concentration in plasma; CMPS-SF: Glasgow composite measure pain scale – short form; NK1: Neurokinin-1; OHE: Ovariohysterectomy; Tmax: Time to Cmax; T1/2: Half-life of terminal elimination phase; VAS: Visual analogue scale

Refractory Dyspnea in a Patient with End-Stage Idiopathic Pulmonary Fibrosis (Palliative Care unit Case Study)

Treating dyspnea in patients with idiopathic pulmonary fibrosis is a challenge. The foreign experience of using low doses of opioids to relieve dyspnea in patients with progressing diseases is controversial among Russian specialists. The presented clinical case is an 83-year-old patient with idiopathic pulmonary fibrosis in the terminal stage and refractory dyspnea, progressive respiratory failure of II - III degrees, and concomitant exertional angina II FC and organic anxiety disorder. The patient was offered low-dose morphine injections (2 mg 5 times a day subcutaneously) to relieve the shortness of breath. The patient, who had not previously received opioids, and his relatives gave prior consent to the use of morphine. Within a week from the moment of hospitalization, the general and psycho-emotional state of the patient improved, dyspnea decreased, and night sleep was partially normalized. However, а week later, being in a severe but relatively stable condition, the patient died from a massive nosebleed. Shown, that the traditional approach to reducing dyspnea and the associated agitation in patients with interstitial lung disease is the use of corticosteroids and psychotropic therapeutics in increasing doses. The use of low doses of opioids to relieve dyspnea in patients with non-cancer disease meets many organizational, medical, and psychological barriers. At the same time, this therapy is recognized as successful and safe in the foreign palliative practice. Overcoming the existing barriers based on the evidence from clinical trials, as well as the domestic and foreign clinical practice of the safe use of low doses of opioids would expand the arsenal of effective treatments for refractory dyspnea.

Comparison and interaction of morphine and CB1 agonist conditioned place preference in the rat model of early life stress.

Early life stress (ELS) disrupts brain development and subsequently affects physical and psychological health. ELS has been associated with an increased risk of relapse and inadequate treatment response in addicted patients. The current study was designed to find the effect of ELS on the rewarding effect of morphine and cannabinoid and their interaction. Pregnant female Wistar rats were used in this study. On postnatal day 2 (PND2), pups were separated from their mothers for 3hr daily. This procedure was repeated every day at the same time until PND 14. The control group was kept in the standard nesting way with their mothers. The adult male offspring of maternal separated (MS) and standard nested (SN) rats were used. Using conditioned place preference task (CPP), the rewarding effect of morphine (0.75, 1.25, 2.5, and 5mg/kg) was evaluated in both MS and SN groups. Besides, the rewarding effect of cannabinoids was investigated using the administration of CB1 receptor agonist (ACPA, 0.25, 0.5, 1µg/rat) and inverse agonist (AM-251, 30, 60, and 90ng/rat) in the nucleus accumbens (NAc). To evaluate the interaction between NAc cannabinoidergic system and morphine, the noneffective dose of ACPA and AM-251 were administered with a noneffective dose of morphine (0.75mg/kg) on both MS and SN animals. Obtained results indicated that MS groups had a leftward shift in the rewarding effect of morphine and conditioned with low doses of morphine. However, they had a rightward shift in the rewarding effect of cannabinoids. In addition, coadministration of noneffective doses of morphine and ACPA potentiate conditioning in both MS and SN groups. Previous evidence shows that ELS induced changes in the brain, especially in the reward circuits. Here, we demonstrated that MS animals are more sensitive to the rewarding effect of morphine compared with SN animals. In addition, ELS disrupts the cannabinoid system and affect the rewarding effect of cannabinoids.

Cost-effectiveness of sustained-release morphine for refractory breathlessness in COPD: A randomized clinical trial.

Chronic breathlessness is a frequent symptom in advanced Chronic Obstructive Pulmonary Disease (COPD) and has major impact on quality of life, daily activities and healthcare utilization. Morphine is used as palliative treatment of chronic breathlessness. The aim is to analyze cost-effectiveness of regular, low-dose morphine in patients with advanced COPD from a healthcare and societal perspective. In a randomized controlled trial, participants with advanced COPD were assigned to 10mg regular, oral sustained-release morphine or placebo twice daily for four weeks. Quality of life (COPD Assessment Test; CAT), quality-adjusted life years (QALY's; EQ-5D-5L), healthcare costs, productivity, and patient and family costs were collected. Incremental cost-effectivity ratio's (ICERs) using healthcare costs and CAT scores, and incremental cost-utility ratio's (ICURs) using societal costs and QALY's were calculated. Data of 106 of 124 participants were analyzed, of which 50 were in the morphine group (mean [SD] age 65.4 [8.0] years; 58 [55%] male). Both ICER and ICUR indicated dominance for morphine treatment. Sensitivity analyses substantiated these results. From a healthcare perspective, the probability that morphine is cost-effective at a willingness to pay €8000 for an minimal clinically important difference of 2 points increase in CAT score is 63%. From a societal perspective, the probability that morphine is cost-effective at a willingness to pay €20,000 per QALY is 78%. Morphine for four weeks is cost-effective regarding the healthcare and the societal perspective. To estimate the long-term costs and effects of morphine treatment, a study of longer follow-up should be performed. ClinicalTrials.gov (NCT02429050).

Low-dose Ketamine For Acute Pain Control in the Emergency Department: A Systematic Review and Meta-analysis.

There has been increased interest in the use of low-dose ketamine (LDK) as an alternative analgesic for the management of acute pain in the emergency department (ED). The objective of this systematic review was to compare the analgesic effectiveness and safety profile of LDK and morphine for acute pain management in the ED. Electronic searches of Medline and EMBASE were conducted and reference lists were hand-searched. Randomized controlled trials (RCTs) comparing LDK to morphine for acute pain control in the ED were included. Two reviewers independently screened abstracts, assessed quality of the studies, and extracted data. Data were pooled using random-effects models and reported as mean differences and risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence. Eight RCTs were included with a total of 1,191 patients (LDK=598, morphine=593). There was no significant difference in reported mean pain scores between LDK and morphine within the first 60minutes after analgesia administration and a slight difference in pain scores favoring morphine at 60 to 120minutes. The need for rescue medication was also similar between groups (RR=1.26, 95% CI= 0.50 to 3.16), as was the proportion of patients who experienced nausea (RR=0.97, 95% CI= 0.63 to 1.49) and hypoxia (RR=0.38, 95% CI= 0.10 to 1.41). All outcomes were judged to have low certainty in the evidence. Low-dose ketamine and morphine had similar analgesic effectiveness within 60minutes of administration with comparable safety profiles, suggesting that LDK is an effective alternative analgesic for acute pain control in the ED.

ROUX-IN-Y GASTROJEJUNAL BYPASS: WHICH ANESTHETIC TECHNIQUE HAS BEST RESULTS?

Nausea and vomiting groups x moments. As the number of bariatric operations increases, there is a greater interest in knowledge, experience and skills in the operative and anesthetic management of obese people. Anesthetic recovery is an important point in the therapeutic approach and less adverse effects delaying discharge of these patients are necessary to be kept in mind by the surgical team. To compare anesthetic-analgesic techniques in the opioid-sparing era through epidural administration of local anesthetic associated with low-dose morphine vs. clonidine and analyze the impact of analgesia on the effectiveness of postoperative recovery by comparing these two techniques. Randomized, double-blind clinical trial with 66 patients candidates for Roux-en-Y gastrojejunal bypass divided into two groups: morphine group and clonidine group. Multimodal analgesia included epidural anesthesia with 0.375% ropivacaine 20 ml at the eighth thoracic vertebra with the association of morphine (morphine group) at a dose of 15 mcg / kg or clonidine (clonidine group) at a dose of 1 mcg / kg. The groups were homogeneous and statistical significance was found when analyzing the difference in pain between them in the first postoperative period. The pain was higher in the clonidine group, as in this period, analgesic rescue was also better in this group. In the other times, there was no significance in the differences regarding pain and rescue. The return of intestinal motility in the morphine group was earlier in the first postoperative period. Nausea, vomiting and hospital discharge did not show significant differences between groups. Epidural anesthesia with low-dose morphine allowed less pain during the entire hospital stay, with a positive impact on patient recovery.

The additional analgesic effects of transverse abdominis plane block in patients receiving low-dose intrathecal morphine for minimally invasive colorectal surgery: a randomized, single-blinded study.

PurposeIntrathecal analgesia (ITA) and transverse abdominis plane block (TAPB) are effective pain control methods in abdominal surgery. However, there is still no gold standard for postoperative pain control in minimally invasive colorectal surgery. This study aimed to investigate whether the analgesic effect could be increased when TAPB, which can further reduce wound somatic pain, was administered in low-dose morphine ITA patients.MethodsPatients undergoing elective colorectal surgery were randomized into an ITA with TAPB group or an ITA group. Patients were evaluated for pain 0, 8, 16, 24, and 48 hours after surgery. The primary outcome was the total morphine milligram equivalents administered 24 hours after surgery. The secondary outcomes were pain scores, ambulatory variables, inflammation markers, hospital stay duration, and complications within 48 hours after surgery.ResultsA total of 64 patients were recruited, and 55 were compared. There was no significant difference in morphine use over the 24 hours after surgery in the 2 groups (ITA with TAPB, 15.3 mg vs. ITA, 10.2 mg; P = 0.270). Also, there was no significant difference in pain scores. In both groups, the average pain score at 24 and 48 hours was 2 points or less, showing effective pain control.ConclusionITA for pain control in patients with colorectal surgery is an effective pain method, and additional TAPB was not effective.

General Anesthesia in Red-footed Tortoise (Chelonoides carbonaria) for Gastric Foreign Body Removal

Background: The anatomical, physiological, and pharmacological characteristics of reptiles make anesthesia in chelonians particularly challenging. Specific literature regarding safe anesthetic protocols that provide immobilization, antinociception, amnesia, and unconsciousness are scarce. Thus, this paper aims to report the case of a red-footed tortoise submitted to long-duration general anesthesia to celiotomy for foreign body removal. Case: An adult red-footed tortoise (Chelonoides carbonaria), 5.9 kg, was admitted due to hyporexia after ingesting a metallic fishhook. Serial radiographs confirmed the diagnosis and location of the foreign body in the stomach. The animal was premedicated with 0.03 mg/kg dexmedetomidine, 6 mg/kg ketamine, and 0.4 mg/kg butorphanol intramuscularly. After 90 min we inserted a 22G jugular catheter and proceeded to anesthesia induction with 5 mg/kg propofol. We intubated the animal with a 2.5 mm uncuffed endotracheal and started fluid therapy at a rate of 5 mL/kg/h. Surgical anesthesia was maintained with isoflurane in 0.21 oxygen, in a non-rebreathing circuit (baraka), under spontaneous breathing. Expired isoflurane was maintained between 3 and 4.5%. Due to reduced respiratory rate and hypercapnia, we opted for implementing manually-assisted positive pressure ventilation. Morphine (0.5 mg/kg) was administered at 10 and 87 min after the beginning of the surgery for further analgesia when the isoflurane requirement increased significantly. We did not detect any alterations in heart and body temperature. Surgical anesthesia lasted 6 h. During anesthesia recovery, voluntary head retraction and coordinated movement of the limbs occurred at 240 and 540 min after the extubation, respectively. In 2 days, the patient returned to voluntary feeding, being very active and responsive to stimulus. The post-surgical hematologic evaluation was unremarkable. Discussion: Pre-anesthetic medication aimed to promote sedation and preemptive analgesia. Due to its minimal cardiorespiratory depression, we chose the combination of ketamine, dexmedetomidine, and butorphanol. Dexmedetomidine reduced the ketamine dose and caused sufficient muscle relaxation and immobilization to perform the jugular catheter placement. Butorphanol is an agonist-antagonist opioid; that is why we decided to add it to the protocol for antinociception. However, due to signs of nociceptive response (increased isoflurane requirements and heart rate), and considering the evidence of a predominance of μ receptors in reptiles, we administered low-dose morphine twice during the procedure. Propofol was chosen as an induction agent at a dose sufficient to allow endotracheal intubation. Since reptilians often show apnea in the presence of 100% oxygen, we used a 0.21 oxygen fraction. Despite this, the patient showed respiratory depression. Due to right to left cardiac shunt, sudden changes in the direction of the blood can lead to very rapid changes in the serum concentrations of isoflurane, which leads to frequent oscillations in the anesthetic depth and consequently the need for vaporizer adjustments, which may justify the high expired isoflurane fraction during the procedure. Despite that, physiological parameters were maintained within normal ranges for the species, with slight variations during the surgical procedure. We conclude that the proposed anesthetic protocol is safe for long-duration anesthesia in chelonians, ensuring cardiovascular and respiratory stability. Thus, this report may help veterinarians to perform safe anesthesia in tortoises submitted to invasive surgical procedures. Keywords: testudines, dexmedetomidine, ketamine, butorphanol. Descritores: testudines, dexmedetomidina, cetamina, butorfanol.

Comparison of low dose intravenous fentanyl and morphine infusion for postoperative analgesia in spine fusion surgeries – a randomized control trial

Background and aimsPost-operative analgesia for Spine surgeries is difficult without patient control analgesia (PCA) and inadequate monitoring facilities. The objective was to study the effectiveness of analgesia of intravenous administration of low dose fentanyl and morphine for postoperative analgesia following spine fusion surgeries. MethodsOne hundred adult patients undergoing spine instrumentation surgeries were randomly allotted into two groups: Group M (morphine) or Group F (fentanyl). The patients received either 0.02 mg.kg-1.h-1 of morphine or 0.3 mcg.kg-1.h-1 of fentanyl infusion postoperatively. If the patient had pain, additional bolus dose of 0.04 mg.kg-1 and 0.6 mcg. kg-1 bolus for morphine and fentanyl respectively were given and noted. The additional analgesic consumption was recorded. The Ramsay sedation score (RSS), visual analogue score (VAS), vital parameters and complications were observed. ResultsThe demographic characteristics did not reveal significant difference among the two groups. In morphine group, 32 patients did not require any additional bolus dose, 15 patients needed one bolus dose and one patient each required two and three boluses. In fentanyl group, two, 24, 20 and four patients required 0, 1, 2 and 3 bolus doses respectively. There were no statistically significant variations in hemodynamic features like heart rate, blood pressure and oxygen saturation, RSS and VAS. The complication rate was not significant among the groups. ConclusionLow dose continuous infusion of morphine is more effective than fentanyl with fewer requirements of rescue analgesics for postoperative analgesia. Both drugs are safe without any serious complications.

Low-Dose Ketamine Infusion Versus Morphine Infusion During Abdominoplasty to Change the Postoperative Pain Profile.

BackgroundWith the increased number of abdominoplasty all over the world, and the need to manage postoperative pain, it is a must to find proper and effective drugs to decrease opioid consumption in the postoperative period.ObjectivesIn this double-blind randomized controlled clinical trial, we assumed that low-dose ketamine infusion will reduce the postoperative pain profile than the conventional method of morphine.MethodsThe scheduled patients for abdominoplasty under general anesthesia were recruited in two groups: group (K) with low-dose ketamine infusion intra-operatively (80 patients) and group (M) with morphine infusion intra-operatively (80 patients). Both groups were monitored intraoperatively and postoperatively for rescue doses of fentanyl, visual analogue scale (VAS), and side effects.ResultsThere were no statistical differences between both groups regarding the fentanyl rescue doses intra- and postoperative with no remarkable side effects.ConclusionsLow-dose ketamine has a useful analgesic effect in abdominoplasty similar to morphine without remarkable side effects, such as sedation or hallucinations.

Low-Dose Ketamine Is a Viable Option for Control of Acute Pain in the ED

To compare the analgesic efficacy of intravenous low-dose ketamine and morphine, researchers performed a systematic review and meta-analysis of

Chronic Low-Dose Morphine to Improve Breathlessness in Patients with COPD?

Data on chronic opioids for breathlessness in patients with chronic obstructive pulmonary disease (COPD) are conflicting, and concern has been raised

Interaction of morphine tolerance with pentylenetetrazole-induced seizure threshold in mice: The role of NMDA-receptor/NO pathway

N-methyl-d-aspartate receptor (NMDA-R)/nitric oxide (NO) pathway is involved in the intensification of the analgesic effect of opioids and the reduction of the intensity of opioids tolerance and dependence. In the current study, we investigated the involvement of NMDA-R/NO pathway in chronic morphine-treated mice in both the development of tolerance to the analgesic effect of morphine and in pentylenetetrazole (PTZ)-induced seizure threshold. Chronic treatment with morphine (30 mg/kg) exhibited increased seizure resistance in morphine-induced tolerant mice. The development of morphine tolerance was withdrawn when used concomitantly with NOS inhibitors and NMDA-R antagonist, suggesting that the development of tolerance to the anticonvulsant effect of morphine (30 mg/kg) is mediated through the NMDA-R/NO pathway. A dose-dependent biphasic seizure modulation of morphine was demonstrated in the acute treatment with morphine; acute treatment at a dose of 0.5 mg/kg shows the anticonvulsant effect and at a dose of 30 mg/kg shows proconvulsant effect. However, a different pattern was observed in the mice treated chronically with morphine: they demonstrated tolerance in the tail-flick test; five consecutive days of chronic treatment with a high dose of morphine (30 mg/kg) showed anticonvulsant effect while a low dose of morphine (0.5 mg/kg) showed a proconvulsant effect. The anticonvulsant effect of morphine was inhibited completely by the concomitant administration of NO synthase (NOS) inhibitors including nonspecific NOS inhibitor (L-NAME, 10 mg/kg), inducible NOS inhibitor (aminoguanidine, 50 mg/kg), and neuronal NOS inhibitor (7-nitroindazole (7-NI), 15 mg/kg) for five consecutive days. Besides, five days injection of NMDA-R antagonist (MK-801, 0.05 mg/kg) significantly inhibited the anticonvulsant effect of morphine on the PTZ-induced clonic seizures.The results revealed that chronic treatment with morphine leads to the development of tolerance in mice, which in turn may cause an anticonvulsant effect in a high dose of morphine via the NMDA-R/NO pathway.

Оценка эффективности и безопасности трамадола и морфина в низких дозах при купировании боли у детей после проведения химиотерапии и трансплантации гемопоэтических стволовых клеток

A sufficient subgroup of patients encounters pain syndrome in the course of cytostatic chemotherapy (ChT), either with or without hematopoietic stem cell transplantation (HSCT). Over this time period, severe thrombocytopenia and leucopenia may develop, thus limiting the opportunities for non-steroidal anti-inflammatory drugs (NSAID). As recommended by WHO, administration of strong opioids to children is possible in moderate pain and inefficiency of NSAIDs. In this case, second step of the pain relief ladder is absent, i.e., codeine application. However, the recommendations do not exclude usage of tramadol, which is widely applied in pediatrics. Our aim was to evaluate relative safety and efficiency of tramadol and morphine in managment of moderate pain in children after HSCT and ChT. Patients and methods The study included analysis of 159 children admitted to the ICU pain management team with complaints for weak or moderate pain (form 3 to 6 points on an age-matched scale). The age of patients was from 1 to 17 years, with a median of 8 years old. All the patients did not receive opioids (were opioid naïve) within 30 days before inclusion to the study. The drugs were injected by continuous infusion at the inpatient clinic. In the first group (n=118), standard tramadol doses were administered as the 1st-line therapy (0.2 to 0.3 mg/kg/h). The patients form 2nd group (n=41) were administered low-dose morphine (0.01 to 0.019 mg/kg/h). Treatment efficiency was assessed by FLACC verbal scores, Wong-Baker Faces Pain Rating Scale, or visual analogue scale and quality of life. Statistical evaluation was performed by means of SPSS software, using a nonparametric Chi-square criterion. Results When administered tramadol as a first-line therapy, it was efficient in ca. 40.7% of cases (n=48). With low-dose morphine, the response rate proved to be 58.5% (n=24). One patient (0.8%) received tramadol when transferred to other institution. The second-line therapy (strong opioids) was administered due to lack of efficiency, or poor drug acceptability during the first-line treatment. It was observed in 53.4% of group 1 (n=63), and in 39% (n=16) of morphine-treated patients (group 2). Side effects due to tramadol administration were observed in 5.1% of cases (n=6). When administered low-dose morphine, only 1 female patient (2.4%) developed intestinal paresis which resolved after the therapy cancellation. Upon statistical evaluation, no significant differences were revealed between the groups. Conclusion Both medical drugs have shown similar efficiency and safety when applied for jugulating weak or moderate nociceptive pain after cytostatic chemotherapy and HSCT in pediatric patients.

Morphine for the symptomatic reduction of chronic breathlessness: the case for controlled release.

Clinicians who seek to reduce the symptomatic burden of chronic breathlessness by initiating regular low-dose morphine has the choice of immediate or sustained-release formulations - which will be better for this often frail population, and which has the more robust evidence to inform its prescription? Both formulations can be used. For chronic breathlessness, three factors consistently favour the use of regular, low-dose, sustained-release morphine over immediate-release formulations: SUMMARY: As the evidence base expands for the symptomatic reduction of chronic breathlessness, pharmacological interventions will play a part. Using the best available evidence underpins patient-centred approaches that seek to predictably maximize the net effect.As such, the weight of evidence in patient-centred clinical care favours the use of regular, low-dose sustained-release morphine for the symptomatic reduction of chronic breathlessness.