Intravenous Administration Of Morphine Research Articles

Morphine concentrations in fatalities after palliative treatment of acute burn injury

The evaluation of a morphine concentration in postmortem blood is routine for a forensic toxicologist. We here report three fatal cases where we found high morphine concentrations with 7.96, 4.30, and 5.82 mg/l in femoral blood that have to be estimated as unusually high. All these individuals died due to severe burn injuries and obtained morphine in the context of their palliative care in the last hours of their lives. According to the autopsy results, the cause of death in case 1 was burn disease with burns of about 90% of the body surface area (BSA), case 2 burn trauma, and case 3 burn shock. Besides morphine, propofol, fentanyl, sufentanil, midazolam, diazepam, lorazepam, cefazolin, and rocuronium were detected in femoral blood. The findings fitted well with the detailed clinical documentation. Further evidence of therapeutic concentrations of quetiapine, duloxetine, and melperone could be matched to preexisting medication of the individuals. Physiologically based pharmacokinetic modelling (PBPK) was applied, developed for the intravenous administration of morphine, to find an explanation for the high morphine concentrations in femoral blood. Quantification of morphine in body fluids and tissue was performed to calculate morphine tissue concentration ratios to the morphine concentration in femoral blood. The presented cases show that pharmacokinetic simulations can reflect decreased renal clearance and decreased hepatic metabolism in general. However, this prediction is not sufficient to explain the high morphine concentrations in femoral blood measured here. It can be assumed that burn shock in particular leads to altered pharmacokinetics, namely decreased distribution of morphine.

Extrapyramidal side effects following intravenous morphine administration in a young patient with sickle cell disease

Extrapyramidal side effects following intravenous morphine administration in a young patient with sickle cell disease

Determination of trace morphine and its metabolites in mouse urine using a TpBD functionalized bivalve magnetic nano-adsorbent.

In this study, a new type of covalent organic framework (TpBD) functionalized bivalved magnetic microsphere (TpBD-DS MNS) adsorbent was applied for the enrichment and detection of trace morphine and its metabolites in mouse urine. The main factors affecting the efficiency of magnetic solid phase extraction were optimized, and the optimal MSPE conditions were obtained. Combined with the UPLC-MS/MS technique, a new method for determining trace morphine and its metabolites in urine was established. The detection (LOD) and quantification (LOQ) limits for morphine and its metabolites ranged from 0.16 pg mL-1 to 0.53 pg mL-1 and 0.26 pg mL-1 to 1.25 pg mL-1, respectively. The recovery of the methods ranged from 87.4-97.3%, and the RSD was less than 5%. By employing this methodology, we successfully obtained the temporal change curve of morphine and its metabolites in mouse urine through collection and measurement post intravenous administration of morphine. This approach not only presents a novel means for investigating pharmacokinetics and drug monitoring but also demonstrates significant potential in the fields of forensic toxicology and drug abuse surveillance.

Insufficient effect of sedation followed by difficulties inducing a colicking Shetland pony

AbstractA Shetland pony suspected of large intestinal displacement was presented for exploratory laparotomy. The pony was extremely agitated with refractory pain despite repeated intravenous administration of detomidine and morphine. As the pony became unmanageable and recumbent, it was decided to induce general anaesthesia as soon as possible to prevent further harm. However, it subsequently proved impossible to obtain adequate anaesthetic depth despite intravenous administration of ketamine/midazolam, propofol and thiopental. Only after endotracheal intubation and administration of isoflurane was a surgical plane of anaesthesia achieved. An anaesthetist may be faced with an unexpected lack of effect of administered anaesthetic drugs, which in equine anaesthesia may lead to dangerous situations for patients and personnel. Possible explanations for the observed events and recommendations for prevention are offered.

Salivary cortisol as a biomarker of stress in surgical patients.

Surgical stress and pain result in activation of hypothalamus-pituitary-adrenal axis. The aim of this study was to establish the effects of postoperative pain and various modalities of analgesic administration on salivary and serum cortisol levels, as well as to establish the validity of salivary cortisol as a stress indicator in surgical patients. A randomized controlled trial involved 60 patients scheduled for elective abdominal aortic aneurysm surgery. Patients were randomly divided into two groups depending on the model of postoperative analgesia. The first group (MI - morphine intermittently) included patients given morphine doses 0.1 mg/kg/6h s.c. intermittently. The second group (MPCA - morphine patient-controlled analgesia) included patients who received morphine via the PCA system - intravenous administration of morphine adjusted to a dose of 1 mg per shot and a lockout interval of 6 minutes.

Periosteal Nerve Block Vs. Intravenous Morphine in Pain Relief of Distal Radius and Ulna Fracture; a Double-Blind Randomized Clinical Trial.

Distal forearm fractures' realignment and fixation is a painful procedure. This study aimed to compare the efficacy of periosteal nerve block and intravenous morphine in distal radius and ulna fractures' pain management. In the present randomized, parallel, double-blind, controlled clinical trial, patients with distal radius or ulna fractures were divided into two groups. In the first group, for periosteal nerve block, 1% lidocaine was injected at a distance of 6 to 8 cm near the wrist from the lateral radius and medial ulna. In the second group, morphine sulfate at a dose of 0.1 mg/kg was slowly injected through the peripheral vein within 5 minutes. The visual analog scale (VAS) score was evaluated before the intervention and every 15 minutes until 90 minutes after the intervention and was compared between the two groups. 75 subjects were studied (39 in the periosteal nerve block and 36 in the intravenous morphine group). There were no significant differences between the groups in terms of mean age (p = 0.384), gender distribution (p = 0.464), past medical history (p = 0.106), trauma type (p = 0.836), fracture type (p = 0.613), and baseline pain severity on VAS (p = 0.987). Both methods reduced the VAS scores during the 90 minutes of the study. The mean pain scores of the patients in the periosteal nerve block group with 2.56±1.44, 2.15±1.11, 2.66±1.26, and 3±1.27 at 15, 30, 45, and 60 minutes after the analgesic injection, respectively, were significantly lower than those of the intravenous morphine group with 4.75±1.27, 4.22±1.22, 3.97±1.27, and 4.13±1.35, respectively (p < 0.001 for all comparisons). In the present study, no local or systemic complications were observed in the periosteal nerve block group, while the complications of dyspnea, vomiting, and pruritus were reported by 5.5%, 2.8%, and 2.8%, respectively, in the intravenous morphine group. Moreover, the percentage of need for additional analgesia in the intravenous morphine group was higher than that of the periosteal nerve block group. In the first hour after the intervention, pain reduction in periosteal block was significantly higher than intravenous morphine administration. Also, the incidence of complications and the need for additional analgesia were lower in the periosteal block group compared to intravenous morphine administration.

Intravenous acetaminophen with morphine versus intravenous morphine alone for acute pain in the emergency room: protocol for a multicenter, randomized, placebo-controlled, double-blinded study (ADAMOPA)

BackgroundIn emergency medicine, pain is a frequent reason for consultation. However, there is a great variation in its management which is often insufficient. The use intravenous morphine alone or multimodal analgesia with paracetamol is recommended for severe pain. But robust data are lacking to justify the association of paracetamol with morphine versus morphine alone for pain management in the emergency room (ER). The aim of our study is therefore to assess if in patients with acute pain of moderate to severe intensity with a numerical verbal scale (NVS) ≥5 in the ER, the intravenous administration of morphine alone is not inferior to the administration of intravenous morphine combined with paracetamol at 30 min from the first administration of the study drug.MethodsADAMOPA is a prospective, non-inferiority, multicenter, placebo-controlled, parallel-group, randomized (1:1), double-blind trial. Subjects will be enrolled in the ER if they experience moderate to severe, acute, non-traumatic, and traumatic pain, defined as an NVS ≥5. The primary endpoint will be the between-group difference in mean change in NVS pain scores among patients receiving the combination of intravenous morphine plus paracetamol or intravenous morphine given alone, measured from the time before administration of the study medication to 30 min later.DiscussionThis trial will determine the clinical utility of the association of paracetamol with morphine for pain management in the emergency room. The ADAMOPA trial will be conducted in accordance with the International Council on Harmonization Good Clinical Practices.Trial registrationEudraCT number: 2019-002149-39. ClinicalTrials.gov identifier: NCT04148495. Date of trial registration: November 1, 2019.

Orthostatic intolerance after intravenous administration of morphine: incidence, haemodynamics and heart rate variability analysis.

Orthostatic intolerance after intravenous administration of morphine: incidence, haemodynamics and heart rate variability analysis.

Intrathecal minocycline does not block the adverse effects of repeated, intravenous morphine administration on recovery of function after SCI

Opioids are among the most effective analgesics for the management of pain in the acute phase of a spinal cord injury (SCI), and approximately 80% of patients are treated with morphine in the first 24 h following SCI. We have found that morphine treatment in the first 7 days after SCI increases symptoms of pain at 42 days post-injury and undermines the recovery of locomotor function in a rodent model. Prior research has implicated microglia/macrophages in opioid-induced hyperalgesia and the development of neuropathic pain. We hypothesized that glial activation may also underlie the development of morphine-induced pain and cell death after SCI. Supporting this hypothesis, our previous studies found that intrathecal and intravenous morphine increase the number of activated microglia and macrophages present at the spinal lesion site, and that the adverse effects of intrathecal morphine can be blocked with intrathecal minocycline. Recognizing that the cellular expression of opioid receptors, and the intracellular signaling pathways engaged, can change with repeated administration of opioids, the current study tested whether minocycline was also protective with repeated intravenous morphine administration, more closely simulating clinical treatment. Using a rat model of SCI, we co-administered intravenous morphine and intrathecal minocycline for the first 7 days post injury and monitored sensory and locomotor recovery. Contrary to our hypothesis and previous findings with intrathecal morphine, we found that minocycline did not prevent the negative effects of morphine. Surprisingly, we also found that intrathecal minocycline alone is detrimental for locomotor recovery after SCI. Using ex vivo cell cultures, we investigated how minocycline and morphine altered microglia/macrophage function. Commensurate with published studies, we found that minocycline blocked the effects of morphine on the release of pro-inflammatory cytokines but, like morphine, it increased glial phagocytosis. While phagocytosis is critical for the removal of cellular and extracellular debris at the spinal injury site, increased phagocytosis after injury has been linked to the clearance of stressed but viable neurons and protracted inflammation. In sum, our data suggest that both morphine and minocycline alter the acute immune response, and reduce locomotor recovery after SCI.

Adverse Effects of Repeated, Intravenous Morphine on Recovery after Spinal Cord Injury in Young, Male Rats Are Blocked by a Kappa Opioid Receptor Antagonist.

Immediately following spinal cord injury (SCI) patients experience pain associated with injury to the spinal cord and nerves as well as with accompanying peripheral injuries. This pain is usually treated with opioids, and most commonly with morphine. However, in a rodent model we have shown that, irrespective of the route of administration, morphine administered in the acute phase of SCI undermines long-term locomotor recovery. Our previous data suggest that activation of kappa opioid receptors (KORs) mediates these negative effects. Blocking KORs with norbinaltorphimine (norBNI), prior to a single dose of epidural morphine, prevented the morphine-induced attenuation of locomotor recovery. Because numerous cellular changes occur with chronic opioid administration compared with a single dose, the current study tested whether norBNI was also effective in a more clinically relevant paradigm of repeated, intravenous morphine administration after SCI. We hypothesized that blocking KOR activation during repeated, intravenous morphine administration would also protect recovery. Supporting this hypothesis, we found that blocking KOR activation in young, male rats prevented the negative effects of morphine on locomotor recovery, although neither norBNI nor morphine had an effect on long-term pain at the doses used. We also found that norBNI treatment blocked the adverse effects of morphine on lesion size. These data suggest that a KOR antagonist given in conjunction with morphine may provide a clinical strategy for effective analgesia without compromising locomotor recovery after SCI.

Evaluating the analgesic and sedative effects of intravenous ketamine versus morphine administration on relieving long/short bone-fracture pain in the upper/ lower limbs; a phase II clinical trial

Introduction: The importance of pain control in patients with limb trauma admitted to emergency departments as well as its complications is among the main concerns in post-emergency care, which contributes to the accelerated improvement of patients’ conditions in a significant manner. Objectives: The present study was to evaluate the analgesic and sedative effects of intravenous (IV) ketamine versus morphine administration on relieving long/short bone-fracture pain in the upper/lower limbs. Patients and Methods: The present study is as a double-blind randomized clinical trial. For this purpose, the effect of ketamine and morphine were initially examined using IV ketamine and morphine administration, respectively, at the doses of 0.4 and 0.1 mg/kg/IV/10 min in patients, aged 18-65 years with limb trauma, and admitted to hospital emergency departments. Afterward, the duration of the analgesic effect, the amount of pain relief, according to the visual analog scale (VAS) outcomes, and the complications for each drug, including apnea, bradycardia, tachycardia, altered level of consciousness, nausea, vomiting, hypertension/hypotension, seizures and disturbed sleep were compared, and then the preferred method was introduced. Results: In this study, 120 patients in total, including 60 cases receiving ketamine and 60 individuals receiving morphine, were recruited. The participants’ age range was between 19 -70 years. The patients’ mean age was 47.04±12.57 years of whom 89 patients (74.2%) were male. The study results indicated that the potency of the low-dose ketamine infusion in relieving pain in patients was comparable to that of morphine. Conclusion: It was concluded that ketamine could be administered as an alternative to IV morphine to reduce long/short bone-fracture pain in the upper/lower limbs. Trial Registration: The trial protocol was authorized by the Iranian Registry of Clinical Trials, (identifier: IRCT20170716035105N3; https://en.irct.ir/trial/26628, ethical code: IR.AJUMS.REC.1396.248).

Low-dose morphine reduces tolerance to central hypovolemia in healthy adults without affecting muscle sympathetic outflow.

Hemorrhage is a leading cause of preventable battlefield and civilian trauma deaths. Low-dose (i.e., an analgesic dose) morphine is recommended for use in the prehospital (i.e., field) setting. Morphine administration reduces hemorrhagic tolerance in rodents. However, it is unknown whether morphine impairs autonomic cardiovascular regulation and consequently reduces hemorrhagic tolerance in humans. Thus, the purpose of this study was to test the hypothesis that low-dose morphine reduces hemorrhagic tolerance in conscious humans. Thirty adults (15 women/15 men; 29 ± 6 yr; 26 ± 4 kg·m-2, means ± SD) completed this randomized, crossover, double-blinded, placebo-controlled trial. One minute after intravenous administration of morphine (5 mg) or placebo (saline), we used a presyncopal limited progressive lower-body negative pressure (LBNP) protocol to determine hemorrhagic tolerance. Hemorrhagic tolerance was quantified as a cumulative stress index (mmHg·min), which was compared between trials using a Wilcoxon matched-pairs signed-rank test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat blood pressure (photoplethysmography) during the LBNP test using mixed-effects analyses [time (LBNP stage) × trial]. Median LBNP tolerance was lower during morphine trials (placebo: 692 [473-997] vs. morphine: 385 [251-728] mmHg·min, P < 0.001, CI: -394 to -128). Systolic blood pressure was 8 mmHg lower during moderate central hypovolemia during morphine trials (post hoc P = 0.02; time: P < 0.001, trial: P = 0.13, interaction: P = 0.006). MSNA burst frequency responses were not different between trials (time: P < 0.001, trial: P = 0.80, interaction: P = 0.51). These data demonstrate that low-dose morphine reduces hemorrhagic tolerance in conscious humans. Thus, morphine is not an ideal analgesic for a hemorrhaging individual in the prehospital setting.NEW & NOTEWORTHY In this randomized, crossover, placebo-controlled trial, we found that tolerance to simulated hemorrhage was lower after low-dose morphine administration. Such reductions in hemorrhagic tolerance were observed without differences in MSNA burst frequency responses between morphine and placebo trials. These data, the first to be obtained in conscious humans, demonstrate that low-dose morphine reduces hemorrhagic tolerance. Thus, morphine is not an ideal analgesic for a hemorrhaging individual in the prehospital setting.

Comparison of cervical epidural morphine with intravenous morphine administration on antinociception in adult horses using thermal threshold testing

ObjectiveTo compare the antinociceptive effects of morphine administered via cervical epidural catheter to intravenously administered morphine using a thermal threshold (TT) testing model in healthy adult horses. Study designProspective, randomized, blinded experimental study. AnimalsA total of six university-owned adult horses. MethodsHorses were instrumented with a cervical (C1–C2) epidural catheter and TT testing device with probes at withers and thoracic limb coronary bands. All horses underwent three TT testing cycles including cervical epidural morphine administration (treatment EpiM; 0.1 mg kg–1), systemic morphine administration (treatment SystM; 0.1 mg kg–1) and no morphine administration (treatment Control). Baseline TT was established prior to treatments, and TT was tested at 15, 30, 60, 90, 120, 150, 180, 240, 300, 360, 420, 480, 600 and 720 minutes following treatment. Horses underwent a 5 day washout period between treatments and the order of treatment was randomized. Differences between treatments were analyzed with repeated measures anova. ResultsSystemic and epidural morphine administration resulted in significantly higher TT values compared with baseline and control treatment. The duration of effect was significantly longer in treatment EpiM (10–12 hours) than in treatment SystM (1.5–2.0 hours). Horses in treatment EpiM had significantly higher TT values at time points 180–600 minutes (withers) and 300–600 minutes (coronary band) than horses in treatment SystM. Conclusions and clinical relevanceCervical epidural administration of morphine provided antinociceptive effects as measured by increased TT for 10–12 hours compared with 1.5–2.0 hours for intravenously administered morphine. No complications or adverse effects were noticed following epidural placement of a C1–C2 catheter and administration of morphine. The use of a cervical epidural catheter can be considered for analgesia administration in treatment of thoracic limb and cervical pain in the horse.

Opioids for Treatment of Pre-hospital Acute Pain: A Systematic Review.

IntroductionAcute pain is a frequent symptom among patients in the pre-hospital setting, and opioids are the most widely used class of drugs for the relief of pain in these patients. However, the evidence base for opioid use in this setting appears to be weak. The aim of this systematic review was to explore the efficacy and safety of opioid analgesics in the pre-hospital setting and to assess potential alternative therapies.MethodsThe PubMed, EMBASE, Cochrane Library, Centre for Reviews and Dissemination, Scopus, and Epistemonikos databases were searched for studies investigating adult patients with acute pain prior to their arrival at hospital. Outcomes on efficacy and safety were assessed. Risk of bias for each included study was assessed according to the Cochrane approach, and confidence in the evidence was assessed using the GRADE method.ResultsA total of 3453 papers were screened, of which the full text of 125 was assessed. Twelve studies were ultimately included in this systematic review. Meta-analysis was not undertaken due to substantial clinical heterogeneity among the included studies. Several studies had high risk of bias resulting in low or very low quality of evidence for most of the outcomes. No pre-hospital studies compared opioids with placebo, and no studies assessed the risk of opioid administration for subgroups of frail patients. The competency level of the attending healthcare provider did not seem to affect the efficacy or safety of opioids in two observational studies of very low quality. Intranasal opioids had a similar effect and safety profile as intravenous opioids. Moderate quality evidence supported a similar efficacy and safety of synthetic opioid compared to morphine.ConclusionsAvailable evidence for pre-hospital opioid administration to relieve acute pain is scarce and the overall quality of evidence is low. Intravenous administration of synthetic, fast-acting opioids may be as effective and safe as intravenous administration of morphine. More controlled studies are needed on alternative routes for opioid administration and pre-hospital pain management for potentially more frail patient subgroups.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00346-w.

The Newest Battlefield Opioid, Sublingual Sufentanil: A Proposal to Refine Opioid Usage in the U.S. Military

There is an ongoing opioid epidemic in the USA, and the U.S. military is not immune to the health threat. To combat the epidemic, the Department of Defense (DoD) and Department of Veterans' Affairs (DVA) issued new clinical practice guidelines and launched the Opioid Safety Initiative aimed at reducing opioid prescriptions. Furthermore, the DoD continually refined opioid protocols for acute pain on the battlefield, evolving from intramuscular morphine to intravenous morphine administration to oral transmucosal fentanyl citrate lollipops (Actiq) to finally sublingual sufentanil tablets (SSTs, Dsuvia). Interestingly, the newest introduction of SSTs into the military sparked great controversy, as there are concerns over the drug's potential for misuse. However, although the opioid crisis may understandably foster an aversion to new candidate opioids, the therapeutic benefits of effective opioids in acute trauma settings should not be overlooked. SSTs may offer an improved analgesic option to meet the battlefield's unmet needs with its non-invasive, sublingual delivery system and favorable pharmacologic properties that mitigate the risk for side effects, addiction, and adverse outcomes. Accordingly, this commentary aims to (1) review the evolution of opioid use on the battlefield and discuss the medical benefits and limitations of SSTs in acute trauma settings, (2) highlight the importance of chronic pain management post-deployment through evidence-based non-opioid modalities, and (3) explore avenues of future research. Ultimately, we propose that SSTs are an important improvement from existing battlefield opioids and that refining, not abandoning, opioid usage will be key to effectively managing pain in the military.

Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Myocardial and Microvascular Injury in Acute Myocardial Infarction: Insights From the Randomized MonAMI Trial.

BackgroundIntravenous morphine administration can adversely affect platelet inhibition induced by P2Y12 receptor inhibitors after acute myocardial infarction. In contrast, some evidence suggests that opioid agonists may have cardioprotective effects on the myocardium. The aim of this prospective, randomized MonAMI (Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Platelet Inhibition in Acute Myocardial Infarction) trial was, therefore, to investigate the impact of morphine with or without metoclopramide coadministration on myocardial and microvascular injury.Methods and ResultsPatients with acute myocardial infarction (n=138) were assigned in a 1:1:1 ratio to ticagrelor 180 mg plus: (1) intravenous morphine 5 mg (morphine group); (2) intravenous morphine 5 mg and metoclopramide 10 mg (morphine+metoclopramide group); or (3) intravenous placebo (control group) administered before primary percutaneous coronary intervention. Cardiac magnetic resonance imaging was performed in 104 patients on day 1 to 4 after the index event. Infarct size was significantly smaller in the morphine only group as compared with controls (percentage of left ventricular mass, 15.5 versus 17.9; P=0.047). Furthermore, the number of patients with microvascular obstruction was significantly lower after morphine administration (28% versus 54%; P=0.022) and the extent of microvascular obstruction was smaller (percentage of left ventricular mass, 0 versus 0.74; P=0.037). In multivariable regression analysis, morphine administration was independently associated with a reduced risk for the occurrence of microvascular obstruction (odds ratio, 0.37; 95% CI, 0.14–0.93 [P=0.035]). There was no significant difference in infarct size (P=0.491) and extent (P=0.753) or presence (P=0.914) of microvascular obstruction when comparing the morphine+metoclopramide group with the control group.ConclusionsIn this randomized study, intravenous administration of morphine before primary percutaneous coronary intervention resulted in a significant reduction of myocardial and microvascular damage following acute myocardial infarction. This effect was not observed in the morphine plus metoclopramide group.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02627950.

Intravenous morphine use in acute heart failure increases adverse outcomes: a meta-analysis.

Intravenous morphine is a controversial treatment for acute heart failure (AHF). This study aimed to evaluate and compare the efficacy of intravenous morphine treatment vs. no morphine treatment in AHF patients. Relevant research conducted before June 2020 was retrieved from electronic databases. One unpublished study of our own was also included. Studies were eligible for inclusion if they compared AHF patients treated with intravenous morphine and patients who did not receive morphine. This meta-analysis included three propensity-matched cohorts and two retrospective analyses, involving a total of 149,967 patients (intravenous-morphine group, n = 22,072; no-morphine group, n = 127,895). There was a non-significant increase in the in-hospital mortality in the morphine group (combined odds ratio [OR] = 2.14, 95% confidence interval [CI]: 0.88-5.23, p = 0.095, I2 = 97.1%). However, subgroup analyse showed that the rate of in-hospital mortality with odds of 1.41 times more likely (95% CI: 1.11-1.80, p = 0.005, I2 = 0%) in those receiving vs. not receiving intravenous morphine. No significant correlation was found between intravenous morphine and invasive mechanical ventilation (OR = 2.19, 95% CI: 0.84-5.73, p = 0.10, I2 = 94.2%; subgroup analysis: OR = 2.24, 95% CI: 0.70-7.21, p = 0.176, I2 = 95.1%) or long-term mortality (hazard ratio = 1.15, 95% CI: 0.96-1.34, p = 0.335; I2 = 8.6%). The administration of intravenous morphine to patients with AHF may be related to in-hospital mortality, but not to invasive mechanical ventilation and long-term mortality.

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.

Physiologically-Based Pharmacokinetic Model of Morphine and Morphine-3-Glucuronide in Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease, is increasing in prevalence. NASH-related alterations in hepatic protein expression (e.g., transporters) and in overall physiology may affect drug exposure by altering drug disposition and elimination. The aim of this study was to build a physiologically-based pharmacokinetic (PBPK) model to predict drug exposure in NASH by incorporating NASH-related changes in hepatic transporters. Morphine and morphine-3-glucuronide (M3G) were used as model compounds. A PBPK model of morphine with permeability-limited hepatic disposition was extended to include M3G disposition and enterohepatic recycling (EHR). The model captured the area under the plasma concentration-time curve (AUC) of morphine and M3G after intravenous morphine administration within 0.82-fold and 1.94-fold of observed values from 3 independent clinical studies for healthy adult subjects (6, 10, and 14 individuals). When NASH-related changes in multidrug resistance-associated protein 2 (MRP2) and MRP3 were incorporated into the model, the predicted M3G mean AUC in NASH was 1.34-fold higher compared to healthy subjects, which is slightly lower than the observed value (1.63-fold). Exploratory simulations on other physiological changes occurring in NASH (e.g., moderate decreases in glomerular filtration rate and portal vein blood flow) revealed that the effect of transporter changes was most prominent. Additionally, NASH-related transporter changes resulted in decreased morphine EHR, which could be important for drugs with extensive EHR. This study is an important first step to predict drug disposition in complex diseases such as NASH using PBPK modeling.

ANALGOSEDATION OF NEWBORNS IN THE INTENSIVE CARE UNIT. HOW TO DEAL WITH PAIN SYNDROME

Introduction. The issue of pain in newborns is becoming increasingly relevant, especially for children in intensive care units. Untreated pain reduces the response to treatment of underlying disease, the deterioration of nursing results, the formation of chronic pain and asthenia in the late periods. Aim. To conduct a comparative analysis of the effectiveness of pain therapy methods in newborns treated in the Anesthesiology and Intensive Care Department. Materials and Methods. A cohort prospective study was conducted, which included 20 full-term infants with pain after long-term surgery for congenital intestinal obstruction. Significantly, the children did not differ in sex, weight, did not have enteric insufficiency and severe comorbidities. Children were divided into two groups depending on the method of anesthesia. Group I (n = 10) - newborns who underwent analgesia by administering morphine intravenously. Group II (n = 10) - newborns to whom morphine was administered enterally in combination with intravenous administration of paracetamol for breakthrough pain. In order to determine the effectiveness of analgesic therapy in the conditions of ICU, we used the checklist for monitoring pain in newborns that we developed. Results. The results of the study show that after intravenous administration of morphine, a sufficient level of analgesia was immediately achieved, whereas the full effect after enteral administration was achieved only on the second day, and there was a need for additional analgesia with paracetamol. However, children who received a tablet in the form of morphine had significantly fewer hemodynamic complications and did not need long-term respiratory support. In addition, in children receiving the intravenous form of morphine, severe withdrawal symptoms were observed on the 7th day of the postoperative period, and newborns required analgesia with paracetamol, while oral administration of glucose during manipulations was sufficient for children of group II. The duration of stay in ICU is significantly shorter in children of group II, which also indicates a better tolerance of intestinal forms of morphine. Our pain monitoring checklist allows you to additionally conduct effective pain diagnostics, evaluate the dynamics of pain, and timely adjust pain therapy. Conclusions. Early diagnosis of pain syndrome is necessary for timely prescription of effective analgesic therapy. The use of tablet morphine in newborns with surgical pathology without enteric insufficiency has fewer complications and has better tolerance. Further studies are needed on the use of enteric forms of morphine in newborns with non-surgical pathology.