Low Doses Of Naloxone Research Articles

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic-assisted total gastrectomy: a randomized controlled trial

BackgroundLow immune function after laparoscopic total gastrectomy puts patients at risk of infection-related complications. Low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study was to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial.MethodsFifty-five patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either a naloxone group (n = 23) or a nonnaloxone group (n = 22). Patients in the naloxone group received 0.05 µg/kg-1.h− 1naloxone from 3 days before surgery to 5 days after surgery via a patient-controlled intravenous injection (PCIA) pump, and patients in the nonnaloxone group did not receive special treatment. The primary outcomes were the rates of postoperative complications and immune function assessed by NK cell, CD3+ T cell, CD4+ T cell, CD8+ T cell, WBC count, neutrophil percentage, and IL-6 and calcitonin levels. The secondary outcomes were the expression levels of TLR4 (Toll-like receptor), IL-6 and TNF-α in gastric cancer tissue.ResultsCompared with the nonnaloxone group, the naloxone group exhibited a lower incidence of infection (in the incision, abdomen, and lungs) (P < 0.05). The numbers of NK cells and CD8+ T cells in the naloxone group were significantly greater than those in the nonnaloxone group at 24 h after surgery (P < 0.05) and at 96 h after surgery (P < 0.05). Compared with those in the nonnaloxone group, the CD3 + T-cell (P < 0.05) and CD4 + T-cell (P < 0.01) counts were significantly lower in the naloxone group 24 h after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly greater in the nonnaloxone group. The levels of IL-6 (P < 0.05) and calcitonin in the nonnaloxone group were significantly greater at 24 h after surgery. At 24 h following surgery, the nonnaloxone group had significantly greater levels of IL-6 (P < 0.05) and calcitonin than did the naloxone group. Compared with those in the naloxone group, the expression levels of TLR4 (P < 0.05) in gastric cancer tissue in the naloxone group were greater; however, the expression levels of IL-6 (P < 0.01) and TNF-α (P < 0.01) in the naloxone group were greater than those in the nonnaloxone group.ConclusionLaparoscopic total gastrectomy patients can benefit from 0.05 ug/kg− 1. h− 1 naloxone by reducing their risk of infection. It is possible that LDN alters the number of cells in lymphocyte subpopulations, such as NK cells, CD3 + T cells, and CD4 + T cells, and the CD4+/CD8 + T-cell ratio or alters TLR4 receptor expression in immune cells, thereby altering immune cell activity.Trial registrationThe trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948).

Low-dose naloxone for prophylaxis of sufentanil-induced choking and postoperative nausea and vomiting.

Sufentanil, a potent opioid, serves as the first option for perioperative analgesia owing to its analgesic effect, long duration and stable hemodynamics, whereas its side effects frequently blunt its application. The intravenous (IV) injection of sufentanil during anesthesia induction has high incidence of choking or bucking reaction, which is defined as sufentanil-induced cough (SIC). Moreover, postoperative nausea and vomiting (PONV) is a common and stressful complication, which is also related to the usage of opioid. High incidence of PONV is reported in the patients with SIC. Hence, we sought to determine whether naloxone, an opioid antagonist, at low dose would decrease the incidences of SIC and PONV. 216 female patients undergoing gynecological laparoscopic operation (<2h) under general anesthesia were recruited in this study, and randomly assigned into two groups: Group N (patients receiving naloxone and Group C (patients receiving vehicle). Sufentanil (0.5μg/kg within 5s) was given in anesthesia induction, and low-dose naloxone (1.25μg/kg) or identical vehicle was initially injected 5min prior to induction, with the incidence and severity of SIC estimated. Subsequently, naloxone or vehicle was continuously infused at the rate of 0.5μg/kg/h in the initiation of operation until the end of the operation, and the transverse abdominal fascia block (TAP) was performed for postoperative analgesia. The PONV profiles such as incidence and the severity, grading, and the frequencies of antiemetic usage within 24h were evaluated, with VAS scores and remedial measures for analgesia during the first 24h postoperatively were recorded. Our results revealed that one bolus of low-dose naloxone prior to the induction significantly mitigated the incidence of SIC, and intraoperative continuous infusion of low-dose naloxone reduced the incidence and the severity of PONV, so that the postoperative VAS scores and further remedial analgesia were not altered. These results not only provide clinical solutions for prophylaxis of SIC and PONV, but also suggests that opioids may act as a key role in both SIC and PONV, whereas opioid antagonist may hit two tasks with one stone. Moreover, further investigations are required to address the underlying mechanism of SIC and PONV. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2200064865].

Low dose naloxone for pruritus in systemic sclerosis: Case series and literature review.

Rationale:Pruritus is a common symptom in patients with systemic sclerosis and has a tremendous effect on the quality of life. Nevertheless, current therapeutic options are limited. The pathogenesis of pruritus in systemic sclerosis is not completely understood; however, opiate-mediated neurotransmission has been postulated to be involved.Patient concerns and diagnosis:We describe 4 female patients with systemic sclerosis suffering from severe pruritus, with an average 5D-itch score of 22.75.Intervention and outcomes:Low-dose oral naloxone was initiated, followed by a significant improvement in the level of pruritus, reaching an average 5D-itch score of 7.5, after 6 and 12 months of treatment. None of the patients experienced side effects.Lessons:Low-dose naloxone plays an important role in the management of pruritus in systemic sclerosis.

The effect of different doses of naloxone on postoperative hyperalgesia in patients who received high-dose remifentanil during hysterectomy procedures; a double-blind randomized clinical trial

BackgroundHyperalgesia is one of the adverse effects of remifentanil, an opioid drug used for reducing pain in surgical procedures. Naloxone is used for reversing the adverse effects of opioids and can reduce this acute and persistent pain after surgery. In the present study, we aimed to investigate the effect of two doses of naloxone (high and low doses) for reducing hyperalgesia after hysterectomy. MethodsIn this single-blinded randomized clinical trial, 72 patients who underwent hysterectomy with ASA class I and II were randomly divided into three groups of 24 participants. All three groups received an intraoperative infusion of 0.4 micrograms/kg/min of remifentanil.One group received 0.02 µg/kg/min naloxone, the other group received 0.05 µg/kg/min naloxone, and the third group received 0.2 cc/kg normal saline instead of naloxone. The results of the visual analogue scale, Ramsay score, and pressure algometry were completed for all participants half an hour before the surgery, one hour, two, and eight hours after the surgery, pethidine requirement, and postoperative nausea/vomiting and the Ramsay score were recorded. Comparison of variables among the groups was performed using one-way ANOVA and posthoc tests by SPSS software, version 21. ResultsThe mean age of the participants was 48.63±9.85 years. The pressure algometry of the right and left forearms and abdomen was different among the three groups after surgery (P<0.05). There was no difference in mean pethidine requirement at recovery and in general, visual analogue scale score, Ramsay score 1 hour and 8 h after the surgery, and the frequency of postoperative nausea and vomiting among the three groups (P>0.05). ConclusionThe similar efficacy and adverse effects of the two doses indicate that the low dose of naloxone is suggested for reducing remifentanil-induced hyperalgesia after hysterectomy.

Accidental Opioid Intoxication in Children Treated With Low Doses of Naloxone: A Case of Fentanyl Patch Exposure and a Case of Morphine Tablet Ingestion

Accidental opioid intoxication in children is a rare affection in morocco, its recognition and management must be immediate to avoid its life threatening complications. In a period of two years (September 2019 - September 2021), two cases of severe opioid intoxication in children have been admitted in the intensive care department of the children’s hospital of Rabat. The first case is a 9 years old child admitted for tonic-clonic seizures with acute respiratory distress due to Fentanyl intoxication after being exposed to a skin patch dosed 75 μg/hour, he required mechanical ventilation and was treated with a bolus of 0,8 mg of Naloxone completed with continuous infusion for 48 hours with favorable evolution and hospital release in 5 days. The second case is a 2 years 5 months old child admitted for decreased consciousness with bradypnea due to morphine intoxication after oral ingestion of 5 extended-release morphine tablets dosed 30 mg each, treated with a single bolus of 0,8 mg of Naloxone with rapid improvement.

Evaluation of the Efficacy of Low-Dose Naloxone for the Prevention of Acute Remifentanil-Induced Hyperalgesia in Patients Undergoing General Anesthesia for Laparotomy

Background: Hyperalgesia is a major complication of continuous or intermittent opioid administration. The evidence suggests that concomitant administration of low-dose naloxone could prevent the development of acute opioid-induced hyperalgesia, with no effect on pain control. Objectives: The current study aimed to assess the effects of intraoperative low-dose naloxone, adding to remifentanil infusion on preventing acute postoperative hyperalgesia in patients undergoing general anesthesia for laparotomy. Methods: In this randomized clinical trial, patients undergoing general anesthesia for laparotomic hysterectomy in a tertiary referral teaching hospital from February to December 2019 were randomly assigned to one of three groups of remifentanil-naloxone (remifentanil 0.3 μg/ kg/min with low-dose naloxone 0.25μg/kg /h prepared in 50 mL of normal saline), remifentanil (0.3 μg/kg/min), and control (receiving 50 mL saline infusion), intraoperatively. Patients and researchers were blinded to the type of intervention. The severity of hyperalgesia, as the main outcome, was evaluated by the static Tactile test. The severity of pain was assessed by visual analogous scale 0.5, 2, 6, 12, and 24 hours after surgery. Results: In total, 75 patients were evaluated. The results showed no difference concerning the independent variables (age, body mass index, hypertension, surgery duration, anesthesia duration, and American Society of Anesthesiologists (ASA) class) between the three groups. Heart rate was significantly different in all study time points between the three groups (P &lt; 0.001), but mean arterial pressure and systolic and diastolic blood pressure showed no significant difference (P &gt; 0.05) throughout the study. Assessment of hyperalgesia using the tactile test revealed a higher incidence of hyperalgesia in the remifentanil group in 0.5, 2, 6, 12, and 24 hours after surgery compared to the other two groups, which was statistically significant between the groups at 0.5, 2, and 6 hours after surgery (P &lt; 0.05). Shivering incidence, Morphine dose in 24 hours post-surgery, morphine dose in the recovery room, and VAS for pain were significantly different during the study between the three groups (P &lt; 0.05). Conclusions: This study demonstrated the efficacy of intraoperative low-dose naloxone (0.25 μg/kg/h) added to remifentanil infusion on reducing the frequency and severity of acute postoperative hyperalgesia in patients undergoing general anesthesia for laparotomy hysterectomy.

Comparison of rates of opioid withdrawal symptoms and reversal of opioid toxicity in patients treated with two naloxone dosing regimens: a retrospective cohort study

Introduction When managing opioid overdose (OD) patients, the optimal naloxone regimen should rapidly reverse respiratory depression while avoiding opioid withdrawal. Published naloxone administration guidelines have not been empirically validated and most were developed before fentanyl OD was common. In this study, rates of opioid withdrawal symptoms (OW) and reversal of opioid toxicity in patients treated with two naloxone dosing regimens were evaluated. Methods In this retrospective matched cohort study, health records of patients who experienced an opioid OD treated in two urban emergency departments (ED) during an ongoing fentanyl OD epidemic were reviewed. Definitions for OW and opioid reversal were developed a priori. Low dose naloxone (LDN; ≤0.15 mg) and high dose naloxone (HDN; >0.15 mg) patients were matched in a 1:4 ratio based upon initial respiratory rate (RR). The proportion of patients who developed OW and who met reversal criteria were compared between those treated initially with LDN or HDN. Odds ratios (OR) for OW and opioid reversal were obtained via logistic regression stratified by matched sets and adjusted for age, sex, pre-naloxone GCS, and presence of non-opioid drugs or alcohol. Results Eighty LDN patients were matched with 299 HDN patients. After adjustment, HDN patients were more likely than LDN patients to have OW after initial dose (OR = 8.43; 95%CI: 1.96, 36.3; p = 0.004) and after any dose (OR = 2.56; 95%CI: 1.17, 5.60; p = 0.019). HDN patients were more likely to meet reversal criteria after initial dose (OR = 2.73; 95%CI: 1.19, 6.26; p = 0.018) and after any dose (OR = 6.07; 95%CI: 1.81, 20.3; p = 0.003). Conclusions HDN patients were more likely to have OW but also more likely to meet reversal criteria versus LDN patients.

Countering Opioid-induced Respiratory Depression in Male Rats with Nicotinic Acetylcholine Receptor Partial Agonists Varenicline and ABT 594.

Opioids can induce significant respiratory depression when administered as analgesics for the treatment of acute, postoperative, and chronic pain. There are currently no pharmacologic means of reversing opioid-induced respiratory depression without interfering with analgesia. Further, there is a growing epidemic of opioid overdose that could benefit from therapeutic advancements. The aim of this study was to test the ability of two partial agonists of α4β2 nicotinic acetylcholine receptors, varenicline (used clinically for smoking cessation) and ABT 594 (tebanicline, developed as an analgesic), to reduce respiratory depression induced by fentanyl, remifentanil, morphine, and a combination of fentanyl and diazepam. Whole body plethysmographic recordings, nociception testing, and righting reflex testing were used to examine ventilation, analgesia, and sedation in adult male Sprague-Dawley rats. Pre-, co-, or postadministration of varenicline or ABT 594 did not alter baseline breathing but markedly reduced opioid-induced respiratory depression. Varenicline had no effect on fentanyl-induced analgesia and ABT 594 potentiated fentanyl-induced analgesia. Specifically, 10-min administration of fentanyl induced a decrease in respiratory rate to 43 ± 32% of control in vehicle group, which was alleviated by preadministration of varenicline (85 ± 14% of control, n = 8, P < 0.001) or ABT 594 (81 ± 36% of control, n = 8, P = 0.001). ABT 594 or varenicline with a low dose of naloxone (1 µg/kg), but not varenicline alone, partially reversed fentanyl-induced lethal apnea, but neither compound provided the very rapid and complete reversal of apnea achieved with high doses of naloxone (0.03 to 1 mg/kg). Administration of varenicline (n = 4, P = 0.034) or ABT 594 (n = 4, P = 0.034) prevented lethal apneas induced by the combination of fentanyl and diazepam. Activation of α4β2 nicotinic acetylcholine receptors by varenicline and ABT 594 counters opioid-induced respiratory depression without interfering with analgesia.

The effect of a low-dose naloxone infusion on the incidence of respiratory depression after intrathecal morphine administration for major open hepatobiliary surgery: a randomised controlled trial.

Intrathecal morphine is an analgesic option for major hepatopancreaticobiliary procedures but is associated with a risk of respiratory depression. We hypothesised that a postoperative low-dose naloxone infusion would reduce the incidence of respiratory depression without an increase in pain scores. Patients scheduled for major open hepatopancreaticobiliary surgery and who were receiving 10μg.kg-1 intrathecal morphine were eligible for inclusion. Patients were allocated randomly to receive a postoperative infusion of naloxone 5μg.kg-1 .h-1 (naloxone group) or saline at an identical infusion rate (control group) until the morning after surgery. Clinicians, nursing staff and patients were blinded to group allocation. The primary outcome measure was the incidence of respiratory depression (respiratory rate <10 breaths.min-1 and/or oxygen saturation <90%). Secondary outcome measures included: arterial partial pressure of carbon dioxide; pain score; requirement for supplemental analgesic; and incidence of nausea and vomiting, pruritus and sedation. In total, data from 95 patients (48 in the naloxone group and 47 in the control group) were analysed. The incidence of respiratory depression was lower in the naloxone group compared with the control group (10/48 vs. 21/47 patients, respectively; p=0.037, relative risk 0.47 (95%CI 0.25-0.87). Maximum pain scores were greater for patients allocated to the naloxone group compared with control (median 5 (95%CI 4-6) vs. 4 (95%CI 2-4), respectively; p<0.001). A low-dose naloxone infusion decreases the incidence of respiratory depression following intrathecal morphine administration in patients having major hepatopancreaticobiliary surgery at the expense of a small increase in postoperative pain.

Effect of low dose naloxone on the immune system function of a patient undergoing video-assisted thoracoscopic resection of lung cancer with sufentanil controlled analgesia \u2014 a randomized controlled trial

BackgroundPerioperative immune function plays an important role in the prognosis of patients. Several studies have indicated that low-dose opioid receptor blockers can improve immune function.MethodsSixty-nine patients undergoing video-assisted thoracoscopic resection of the lung cancer were randomly assigned to either the naloxone group (n = 35) or the non-naloxone group (n = 34) for postoperative analgesia during the first 48 h after the operation. Both groups received sufentanil and palonosetron via postoperative analgesia pump, while 0.05 μg·kg− 1·h− 1 naloxone was added in naloxone group. The primary outcomes were the level of opioid growth factor (OGF) and immune function assessed by natural killer cells and CD4+/CD8+ T-cell ratio. Second outcomes were assessed by the intensity of postoperative pain, postoperative rescue analgesia dose, postoperative nausea and vomiting (PONV).ResultsThe level of OGF in the naloxone group increased significantly at 24 h (p<0.001) and 48 h after the operation (P < 0.01). The natural killer cells (P < 0.05) and CD4+/CD8+ T-cell ratio (P < 0.01) in the naloxone group increased significantly at 48 h after the operation. The rest VAS scores were better with naloxone at 12 and 24 h after operation(P < 0.05), and the coughing VAS scores were better with naloxone at 48 h after the operation(P < 0.05). The consumption of postoperative rescue analgesics in the naloxone group was lower (0.00(0.00–0.00) vs 25.00(0.00–62.50)), P < 0.05). Postoperative nausea scores at 24 h after operation decreased in naloxone group(0.00 (0.00–0.00) vs 1.00 (0.00–2.00), P < 0.01).ConclusionInfusion of 0.05 μg·kg− 1·h− 1 naloxone for patients undergoing sufentanil-controlled analgesia for postoperative pain can significantly increase the level of OGF, natural killer cells, and CD4+/CD8+ T-cell ratio compared with non-naloxone group, and postoperative pain intensity, request for rescue analgesics, and opioid-related side effects can also be reduced.Trial registrationThe trial was registered at the Chinese Clinical Trial Registry on January 26, 2019 (ChiCTR1900021043).

The Effect of Adding Low-Dose Naloxone to Intrathecal Morphine on Postoperative Pain and Morphine Related Side Effects after Cesarean Section: A Double-Blind, Randomized, Clinical Trial

BACKGROUND:Nowadays, spinal anaesthesia is a suitable choice for most elective and emergency cesarean section (C-section) deliveries.AIM:This study aimed to determine the effect of adding low-dose naloxone to intrathecal morphine on postoperative pain and morphine related side effects after C-section.MATERIAL AND METHODS:In the present double-blind, randomised clinical trial, 70 women aged over 18 years, who were candidates for elective medical C-section under spinal anaesthesia were selected and randomly assigned to either the study group or the control group. For spinal anaesthesia, 10 mg of Bupivacaine plus 100 μg of morphine was administered for all patients. However, patients in the study group received 20 µg of naloxone intrathecally; but the patients in the control group only received normal saline as a placebo. After surgery, patient-controlled analgesia (PCA) pump with paracetamol (Apotel®) was connected to each patient. The intensity of postoperative pain in the patients was evaluated and recorded using Visual Acuity Screening (VAS) at 2, 4, 6 and 24 hours after the surgery. The patients were also examined for postoperative nausea and pruritus.RESULTS:Regardless of the groups to which the patients were assigned, a significant difference in pain intensity was observed during the study period (time effect; p < 0.001). Although the intensity of pain was lower in the study group, the difference was not statistically significant (group effect; p = 0.84). Also, there was no group time interaction between pain intensity and the times studied (p = 0.61). The incidence rates of postoperative nausea and pruritus were significantly lower in the study group compared to the control group (p < 0.001).CONCLUSION:According to the results of this study, adding low dose naloxone to intrathecal morphine did not significantly change postoperative pain intensity in the patients undergone elective C-section using spinal anaesthesia; however, significantly decreased the severity of postoperative nausea and pruritus.

Low-Dose Versus High-Dose Postoperative Naloxone Infusion Combined With Patient-Controlled Analgesia for Adolescent Idiopathic Scoliosis Surgery: A Randomized Controlled Trial

Study DesignRandomized controlled trial. ObjectivesThe aim of this prospective randomized clinical trial was to compare low (0.5 μg/kg/h) and high (2.5 μg/kg/h) dose naloxone infusion on the time to tolerate liquids and meals after surgery, patient-controlled analgesia (PCA) opioid requirements, nausea and pruritus ratings, and hospital length of stay. Summary of Background DataAdolescents undergoing posterior spinal fusion often receive PCA after surgery and may experience common opioid-associated side effects, including nausea and pruritus. Low-dose naloxone infusion has been shown to reduce the incidence of pruritus and nausea while preserving analgesia, although an ideal dose has not been determined. Less is known about the potential for naloxone to improve bowel function after surgery. MethodsEighty-four patients (age 10–21 years) were randomly allocated to receive low- or high-dose naloxone infusion postoperatively. Surgical anesthetic consisted of propofol and opioid infusion with intrathecal morphine (10–15 μg/kg) at the conclusion of surgery. A visual analog scale (VAS) was used to rate nausea and pruritus. ResultsThe groups had similar time to oral liquid intake after surgery and transition from PCA to oral pain medication. The VAS scores for pruritus and nausea were also similar, as was the need to treat these side effects. Morphine equivalents were similar between groups on postoperative day (POD) 0 and 1. On POD 2, the high-dose infusion group had significantly greater PCA bolus use (1.41±0.9 vs. 1.04±0.6; p<.05), although pain scores did not differ significantly. Hospital length of stay was similar for the two groups. ConclusionHigh-dose naloxone infusion was associated with similar rates of opioid side effects as low-dose. Increased PCA use noted on POD 2 may represent partial reversal of opioid analgesia in the high-dose naloxone group. Level of EvidenceLevel 1.

R6 Low vs Moderate Dose Naloxone Infusion: A Randomized Clinical Trial

R6 Low vs Moderate Dose Naloxone Infusion: A Randomized Clinical Trial

The Effect of Epidural Morphine-Bupivacaine Combined with a Low Dose of Naloxone on Respiratory Function and Analgesia in Patients with Chronic Low-Back Pain

Context: Hypoventilation and apnea after epidural morphine is a serious concern after surgery and an issue in chronic pain. A low dose of naloxone added to morphine can prevent this complication. Objective: To determine that the low dose of naloxone added to epidural morphine analgesic could change the effect of this opioid in chronic low back pain. In addition, we evaluate its effect on respiratory function and patient satisfaction. Patients: Twenty-seven adults suffering from chronic low back pain (LBP) who were candidates for epidural injection treatment. Intervention: This was a randomized double-blind, uniform crossover, controlled clinical trial. The patients were treated with mixture of morphine-bupivacaine and mixture of morphine-bupivacaine-naloxone. Main outcome measure: The primary goals were to evaluate pain intensity and respiratory function after epidural injection of morphine or morphine combined with naloxone. Secondary end-points were the incidence and the side effects (pruritus, nausea, vomiting, and urinary retention) of neuraxial injection of morphine or morphine combined with naloxone for 14 days after each epidural injection. Results: There was no significant difference between morphine and morphine combined with naloxone on mean peripheral capillary oxygen saturation (SpO2m), the lowest peripheral capillary oxygen saturation (SpO2), and the respiratory disturbance index (RDI). Morphine combined with naloxone seemed to decrease pain more than morphine alone, but the result was not significant (p=0.2116). In the group that received morphine and naloxone, pain decreased sooner by half from baseline pain (at day 2 versus at day 6) than the other group. Vomiting, pruritus, and urinary retention were seen with no significant difference in both groups. Conclusion: We conclude that epidural administration of naloxone can preserve the analgesic effect of morphine in treatment of chronic LBP. Naloxone does not have any effects on respiratory function. It reduces itching, nausea, and pruritus after epidural injection of morphine. We cannot be certain whether this is the ideal dose or whether any changes in the doses might produce fewer side effects without interfering with analgesia.

Comparison of Low versus Medium Dose Naloxone Infusion Combined with Patient Controlled Analgesia After Posterior Spinal Fusion and Instrumentation for Adolosecent Idiopathic Scoliosis: A Randomized Controlled Trial

Comparison of Low versus Medium Dose Naloxone Infusion Combined with Patient Controlled Analgesia After Posterior Spinal Fusion and Instrumentation for Adolosecent Idiopathic Scoliosis: A Randomized Controlled Trial

Ultra-low-dose Naloxone as an Adjuvant to Patient Controlled Analgesia (PCA) With Morphine for Postoperative Pain Relief Following Lumber Discectomy: A Double-blind, Randomized, Placebo-controlled Trial.

Lumbar discectomy is one of the most commonly performed neurosurgical procedures. Many patients experience postoperative pain after lumbar discectomy. This study evaluated the effect of ultra-low-dose naloxone infusion on pain intensity after lumbar discectomy in individuals receiving patient-controlled analgesia (PCA) with morphine. In a double-blind, randomized, controlled trial, a total of 80 patients scheduled for open discectomy was randomly assigned to receive naloxone (group N) or placebo (group P). After surgery, all patients were connected to a morphine PCA pump. Both groups received 500 mL of normal saline using a continuous infusion pump through a separate intravenous line for 24 hours. However, group N received a total dose of 0.25 μg/kg/h naloxone, which was added to the normal saline infusion. All patients were asked to grade the intensity of their pain, severity of nausea, vomiting, and pruritus on a 0 to 10 visual analog scale before being discharged from the postanesthesia care unit and at 1, 6, 12, and 24 hours postoperatively. It was observed that both groups had a statistically significant (P<0.01) time trend difference for pain, nausea, and pruritus scores. A significant difference was found between the 2 groups in terms of intensity of pain, nausea, and pruritus, with the naloxone group experiencing a lower level in comparison with the placebo group. Moreover, the median (interquartile range) of morphine consumption after surgery for patients who received naloxone was 26 (24.25 to 28) mg, which is significantly (P<0.001) lower than for the placebo group, which had a median (interquartile range) of 34 (32 to 36) mg. It is concluded that infusion of ultra-low-dose naloxone (0.25 μg/kg/h) along with morphine PCA can significantly reduce pain intensity, morphine consumption, and opioid-induced nausea and pruritus after lumbar discectomy.

The application of combining low dose naloxone with ropivacaine in supraclavicular brachial plexus block

Objective: To observe the effect of low dose naloxone combinewith ropivacaine for supraclavicular brachial plexus block. Methods: Seventy patients undergoing elective upper limb surgery were randomly divided into two groups, ropivacaine group (Group R, n=35) and naloxone group (Group N, n=35). An ultrasound guided technique was used in both two groups.The onset and duration time of sensory and motor blockade, visual analog score(VAS)of 3, 6, 12, 18, 24 h postoperatively, time of first request fordezocine, total amount of dezocine needed, incidence of nausea and vomiting postoperatively(PONV) and patients' satisfaction score for analgesia in 24 h after surgery were measured.At the same time, blood samples were taken before anesthesia, 6 h, 24 h after operation for inspecting the concentration of β-endorphin(β-EP)in plasma. Results: The duration of sensory and motor blockade, time of first request for dezocine in Group N were 736.0(713.5, 836.5), 514.5(491.3, 572.8), 708.5(683.2, 877.0)min, which were all prolonged compared to Group R(522.0(469.5, 606.5), 401.0(370.0, 458.5), 570.0(435.0, 618.5)min)(Z=-6.844, -6.758, -6.700, all P<0.01). The 6, 12, 18 h postoperatively VAS of Group N were 0, 5.0(3.0, 5.8), 5.0(5.0, 6.0)point. Among which the 6, 12 h postoperatively VAS of Group N were lower than that of Group R(1.0(1.0, 3.5), 6.0(6.0, 7.0)point)(Z=-6.596, -4.864, all P<0.01), while the 18 h postoperatively VAS was higher than that of Group R (5.0(4.0, 5.0)point)(Z=-2.603, P<0.01). Total amount of dezocine needed in Group N in 24 h after surgery was 7.5(5.0, 10.0)mg, which was lower than that of Group R(10.0(10.0, 15.0)mg)(Z=-3.449, P<0.01). The incidence of PONV after surgery in Group N was 21.9%, which was lower than that of Group R(45.5%)(χ(2)=4.034, P<0.05). Ptients' satisfaction score for analgesia in 24 h after surgery in Group N was 8.0(7.0, 8.0)point, which was higher than that of Group R(7.0(6.0, 7.0)point)(Z=-3.509, P<0.01). At 6 h postoperatively , the concentration of plasma β-EP in Group N was(113.34±12.36)μg/L, lower than that of Group R((147.14±11.65)μg/L)(t=-7.694, P<0.01). Conclusion: Low dose naloxone combine with ropivacaine for supraclavicular brachial plexus block, prolong the duration of sensory and motor blockade without affecting the onset time.

Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial

BackgroundIntraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone. MethodsPatients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml−1 remifentanil with 0.05 μg kg−1 h−1 naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml−1 remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery. ResultsThe pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22–3.84) vs 3.84 (3.76–4.00) vs 3.80 (3.69–4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups. ConclusionsThe intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain. Clinical trial registrationNCT02856087.

Low-Dose Naloxone for Prophylaxis of Postoperative Nausea and Vomiting: A Systematic Review and Meta-analysis.

To determine whether postoperative administration of low-dose intravenous naloxone decreases the incidence of postoperative nausea and vomiting (PONV) and its impact on postoperative opioid requirements and pain scores. Meta-analysis of nine randomized controlled trials. A total of 946 adult and pediatric patients who received low-dose intravenous naloxone for 24 hours after various surgeries. Systemic literature searches of the Cochrane Central Register of Controlled Trials, Evidence-Based Medicine Reviews, PubMed, and Ovid MEDLINE databases were conducted. Among the relevant studies, data extraction and bias assessment determined the trials for inclusion in this meta-analysis. Nine randomized controlled trials met inclusion criteria. Naloxone demonstrated a reduced risk of postoperative nausea (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.67-0.95, p=0.01) in a pooled analysis of eight of the nine studies. However, naloxone did not decrease the risk of postoperative vomiting in a collective assessment of all nine trials (RR 0.83, 95% CI 0.63-1.09, p=0.18). Subgroup analysis of continuous-infusion naloxone found further reductions in nausea and vomiting, but these findings were limited to 186 of the 946 patients. Three studies recorded antiemetic doses and found an overall dose reduction (RR 0.64, 95% CI 0.42-0.96, p=0.03). Compared with controls, naloxone prophylaxis of PONV did not significantly change cumulative postoperative opioid needs (mean difference 0.29 mg, 95% CI -3.55 to 4.13 mg, p=0.88) among five trials, nor visual analog scale pain scores (mean difference -0.11, 95% CI -0.26 to 0.05, p=0.18) in six studies. This pooled analysis of data suggests that low-dose naloxone plays no role in preventing PONV, while exhibiting no significant effects on postoperative opioid needs and pain scores. The reduction demonstrated in postoperative nausea did not translate into decreases in postoperative vomiting.

Effect of naloxone on intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy.

This study aims to evaluate the effect of naloxone on intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy under total intravenous anesthesia.A total of 90 patients, who underwent intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy under total intravenous anesthesia, were included into this study. All patients were randomly divided into 3 groups (each group, n=30): naloxone group (naloxone+fentanyl), tropisetron group (tropisetron+fentanyl), and fentanyl group (fentanyl). Patients in each group were given a corresponding dose of naloxone. Postoperative analgesia effect and the incidence of side effects such as nausea and vomiting were observed.Small doses of naloxone or tropisetron combined with fentanyl used for intravenous patient-controlled analgesia can significantly reduce the incidence of nausea and vomiting. Six hours after surgery, visual analogue scale (VAS) scores were significantly lower in patients that underwent intravenous patient-controlled analgesia using low-dose naloxone combined with fentanyl compared with patients who received fentanyl alone; however, the postoperative analgesic effect of tropisetron was not observed. Compared with the combination of tropisetron and fentanyl, low-dose naloxone combined with fentanyl can obviously reduce the incidence of nausea and vomiting in patients who underwent intravenous patient-controlled analgesia after laparoscopic cholecystectomy, and enhance the analgesic effect of fentanyl 6 hours after surgery.Low-dose naloxone can reduce the incidence of nausea and vomiting in patients who underwent laparoscopic cholecystectomy under total intravenous anesthesia, and exhibits a certain synergic analgesic effect.