Intravenous Naloxone Research Articles

ALL SUGARS ARE NOT SWEET

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Extravasation of vesicants occurs when there is leakage from a vessel into the surrounding area, with the potential to cause tissue necrosis. Common vesicants include vasopressors, alkylating chemotherapeutic agents, hyper-osmolar or hypo-osmolar agents, and certain antibiotics (vancomycin). Dextrose, at concentrations greater than 10% (D10), is also considered a vesicant, with rates of extravasation from 50% dextrose (D50) varying between 10-30% (1). CASE PRESENTATION: A cachectic 48-year-old with a history of HIV and alcohol and IV drug use, presented with lethargy. Upon initial assessment, she had track marks on her arms and was only responsive to sternal rub, with her exam otherwise unremarkable. She briefly improved with intravenous naloxone but ultimately required intensive care unit admission following intubation for airway protection. The toxicology screen was positive for methadone, opioids, and alcohol. Initial labs revealed ALT of 118 units/L, AST of 94 units/L, hemoglobin of 9.5 g/dL, and albumin of 2.3 g/dL. She was started on thiamine, multivitamin, and folate supplements. Despite starting tube feeds, fingerstick (FS) glucose was consistently low, dropping to 35 mg/dL. She received 2 ampules of 50 mL (25 g) 50% dextrose through a 22-gauge antecubital peripheral IV line, with FS improving to 220 mg/dL after 10 minutes. Two hours later, extensive swelling and fluid-filled blisters were noted throughout the forearm and hand, with Doppler ultrasound revealing the absence of a radial pulse. Her arm was elevated, a cold compress was applied, and a local subcutaneous injection of hyaluronidase was administered. Compartment pressures remained within normal limits, and a repeat Doppler ultrasound after an hour showed reappearance of a right radial pulse. The patient's swelling and blisters improved over the next few days. DISCUSSION: To the best of our knowledge, there are only three published cases on D50 extravasation so far, where D50 was administered by initial paramedic responders, in the field, in an emergent setting (1,2,3). D10 has a similar median time to recovery and post-treatment Glasgow Coma Scale, but with a decreased risk of rebound hyperglycemia. In our case, as the hypoglycemia incident occurred in an intensive care unit, administering D10 would have been a better option, as frequent FS monitoring would have been possible to assess response. Fortunately, close monitoring allowed for early recognition, prompt treatment, and good outcome. CONCLUSIONS: Hypoglycemia is a frequently encountered complication in a critical care setting. This case emphasizes the importance of early detection and treatment when suspecting extravasation of D50 to prevent the development of serious complications. D10 is now emerging as a safer and equally effective alternative to D50 and could become the standard of care for hypoglycemia management. REFERENCE #1: Wiegand R, Brown J. Hyaluronidase for the management of dextrose extravasation. Am J Emerg Med. 2010 Feb;28(2):257.e1-2. doi: 10.1016/j.ajem.2009.06.010. PMID: 20159411. REFERENCE #2: Chinn M, Colella MR. Prehospital Dextrose Extravasation Causing Forearm Compartment Syndrome: A Case Report. Prehosp Emerg Care. 2017 Jan-Feb;21(1):79-82. doi: 10.1080/10903127.2016.1209263. Epub 2016 Sep 6. PMID: 27598324. REFERENCE #3: Lawson SL, Brady W, Mahmoud A. Identification of highly concentrated dextrose solution (50% dextrose) extravasation and treatment--a clinical report. Am J Emerg Med. 2013 May;31(5):886.e3-5. doi: 10.1016/j.ajem.2012.12.010. Epub 2013 Apr 18. PMID: 23602753. DISCLOSURES: No relevant relationships by Natasha Garg, source=Web Response No relevant relationships by Archana Pattupara, source=Web Response No relevant relationships by Adam Rothman, source=Web Response No relevant relationships by DISHANT SHAH, source=Web Response

All Sugars are Not Sweet

Background: Extravasation is defined as the leakage of drugs from the vessel to the surrounding area with the potential to cause tissue necrosis. Such drugs (known as vesicants) that can extravasate include vasopressors, alkylating chemotherapeutic agents, hyperosmolar or hypo-osmolar agents, and certain antibiotics (vancomycin) [1]. Dextrose, at concentrations of 10% or greater, is also considered to be a vesicant, with rates of extravasation from 50% dextrose (D50) injections varying between 10–30% [2]. Case Report: A cachectic 48-year-old female with a past medical history of HIV, former IV drug use, and alcohol use, presented with lethargy. Upon initial assessment, she had track marks on her arms and was only responsive to sternal rub, with her exam otherwise unremarkable. She briefly improved with intravenous naloxone but ultimately required intensive care unit admission following intubation for airway protection. The toxicology screen was positive for methadone, opioids, and alcohol. Initial labs revealed ALT of 118 units per liter, AST of 94 units per liter, hemoglobin of 9.5 grams per deciliter, and albumin of 2.3 grams per deciliter. She was started on thiamine, multivitamin, and folate supplementation, and despite starting tube feeds, glucose measurements were consistently low (with the lowest reading of 35 milligrams per deciliter). She received 2 ampules of 50 milliliters (25 grams) 50% dextrose through a 22-gauge antecubital peripheral IV line, with fingerstick improving to 220 milligrams per deciliter after 10 minutes. Two hours later, extensive swelling and fluid-filled blisters were noted throughout her right forearm and hand, with Doppler ultrasound revealing the absence of a radial pulse (Figure 1). Her arm was elevated, a cold compress was applied, and a local subcutaneous injection of hyaluronidase was administered. Compartment pressures remained within normal limits, and a repeat Doppler ultrasound after one hour revealed reappearance of the right radial pulse. The patient’s swelling and blisters improved gradually over the next few days. Discussion: To the best of our knowledge, there is only one published case on D50 extravasation so far. It describes a 57-year-old female who received D50 in the field for hypoglycemia. She developed extravasation injury and was subsequently diagnosed with compartment syndrome, ultimately requiring fasciotomy. In our case, however, because the incident occurred in-hospital, it was recognized early, the patient was treated with hyaluronidase, and her symptoms self-resolved. Conclusion: This case emphasizes the importance of early detection and treatment when suspecting extravasation of D50 in order to prevent the development of serious complications like compartment syndrome. 10% dextrose (D10) is now emerging as a safer (given the lower concentration) and equally effective alternative to D50 administration and could become the standard of care for hypoglycemia management [3].

Heroin intoxication in a dog

AbstractAn 11‐month‐old intact male boxer cross was presented unconscious following oral heroin consumption. At home, intramuscular naloxone given by the owner showed no obvious improvements. Intravenous naloxone given in the hospital quickly reversed the clinical signs. The owners were not able to afford hospitalisation and the animal was discharged against medical advice. No signs of rebound opioid toxicity were reported. This case report describes the clinical presentation and treatment of a case of heroin intoxication in a dog.

A Fatal Case of Opioid Intoxication After Raw Poppy Plant Ingestion

Papaver somniferum contains many opioids and is frequently used in agriculture. Both the intoxication and the withdrawal of opioids have a wide range of symptoms such as coma, depressed respiration and agitation. Here, a fatal case of opioid intoxication will be presented. A four-year-old female patient was admitted to the pediatric intensive care unit after ingesting raw poppy plants. She had shallow respiration, tachycardia, hypertension and muscle cramps. A high plasma opioid level was measured and bolus intravenous naloxone was administered which resulted in a brief gain of consciousness. She was intubated after a sudden respiratory depression and loss of consciousness 10 hours later. Naloxone infusion was started and continued for two days. She developed disseminated intravascular coagulation and was lost on day twelve. Raw plant ingestion proves difficult to treat since there is less information about the ingredients. Having no consensus on naloxone dosage and intrinsic complications such as hypo- and hypertension, redistribution, rhabdomyolysis and dysmotility disrupts naloxone administration. Ingestion of opioids as plants brings out different complications for the treatment course while deciding on naloxone dosage proves opioid intoxication difficult to treat.

Potential role of ghrelin on the micturition reflex in rats.

IntroductionThe aim of this study was to investigate the effects of intravenous ghrelin administration on the micturition reflex in rats.Material and methodsContinuous cystometrograms were performed with female Sparague-Dawley rats under urethane anesthesia. Stable micturition cycles were established, and ghrelin was then administered intravenously to evaluate changes in bladder activity. In this experiment investigating the role of opioid systems, ghrelin was administered intravenously at the time of first observed bladder contraction after intravenous administration of naloxone methiodide, an opioid receptor antagonist.ResultsIntravenous administration of ghrelin increased intercontraction interval that was dose-dependent. These inhibitory effects returned to pre-controls level within 80 minutes of administration. Similarly, intravenous administration of ghrelin increased threshold pressure in a dose-dependent fashion. These inhibitory effects of ghrelin were antagonized by intravenous naloxone methiodide administration.ConclusionsThese results show that ghrelin inhibits the micturition reflex through an opioid-dependent mechanism in rats under urethane anesthesia.

Are endogenous opioid mechanisms involved in the effects of aerobic exercise training on chronic low back pain? A randomized controlled trial.

Aerobic exercise is believed to be an effective chronic low back pain (CLBP) intervention, although its mechanisms remain largely untested. This study evaluated whether endogenous opioid (EO) mechanisms contributed to the analgesic effects of an aerobic exercise intervention for CLBP. Individuals with CLBP were randomized to a 6-week, 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 44). Before and after the intervention, participants underwent separate laboratory sessions to assess responses to evoked heat pain after receiving saline placebo or intravenous naloxone (opioid antagonist) in a double-blinded, crossover fashion. Chronic pain intensity and interference were assessed before and after the intervention. Endogenous opioid analgesia was indexed by naloxone-placebo condition differences in evoked pain responses (blockade effects). Relative to controls, exercise participants reported significantly greater pre-post intervention decreases in chronic pain intensity and interference (Ps < 0.04) and larger reductions in placebo condition evoked pain responsiveness (McGill Pain Questionnaire-Short Form [MPQ]-Total). At the group level, EO analgesia (MPQ-Total blockade effects) increased significantly pre-post intervention only among female exercisers (P = 0.03). Dose-response effects were suggested by a significant positive association in the exercise group between exercise intensity (based on meeting heart rate targets) and EO increases (MPQ-Present Pain Intensity; P = 0.04). Enhanced EO analgesia (MPQ-Total) was associated with a significantly greater improvement in average chronic pain intensity (P = 0.009). Aerobic exercise training in the absence of other interventions appears effective for CLBP management. Aerobic exercise-related enhancements in endogenous pain inhibition, in part EO-related, likely contribute to these benefits.

Inflammatory Response to Chronic Opioid Exposure in Humans

Abstract Objective In this study, we investigated if chronic opioid exposure leads to changes in immune signaling pathways. Method We used phospho-flow cytometry to study intracellular signaling in immune cells of patients with chronic opioid exposure. PBMCs were stimulated with cytokines (IFN-α, IFN-γ, IL-2, IL-6, IL-7, IL-10, IL-21), then stained to analyze 6 lymphocyte subsets and monocytes for phosphorylated STATs (signal transducers and activators of transcription), in particular p-STATs 1, 3 and 5. Results After one month of opioid exposure as compared to baseline, IL-2 stimulation of B cells resulted in significantly elevated pSTAT3 levels whereas IFN-γ stimulation resulted in significantly reduced pSTAT5 levels. CD4+ T cell subsets showed reduced pSTAT3 induction in response to multiple cytokine stimuli, and reduced pSTAT1 and pSTAT5 induction with IFN-γ. Similar reductions in pSTAT3 and pSTAT5 induction were seen in CD8+CD45RA+ T cells with several cytokine stimuli. In monocytes, IL-7 and IL-21 stimulation resulted in significantly decreased pSTAT1 levels. No significant changes in pSTAT signaling was found in non-B non-T cells after stimulation with various cytokines. In addition, acute opioid withdrawal via intravenous naloxone resulted in significantly increased pSTAT1 and pSTAT5 levels after IFN-γ stimulation in CD8+ T cells. Conclusion One month of opioid exposure significantly reduced cytokine-induced levels of phospho-STAT signaling. These findings suggest that chronic opioid exposure suppresses immune signaling pathways.

Is there enough naloxone to deter the diversion? Effect of concurrent administration of intravenous naloxone on opioid agonist effects of intravenous buprenorphine: A randomised, double-blind, within-subject, crossover study among opioid-dependent subjects.

We aimed to evaluate and compare the effect of different intravenous doses of naloxone on reinforcing effect of intravenous buprenorphine (2 mg) in patients stabilised on sublingual buprenorphine. This is a double-blind, within-subject, randomised, crossover study. Opioid-dependent patients, with history of intravenous drug use, stabilised on buprenorphine maintenance treatment were included after informed consent (n = 14). We administered and assessed the reinforcing effects of six test conditions: buprenorphine and naloxone co-formulation (BNX) in 4:1, 2:1 and 1:1 dose ratio (i.e. buprenorphine 2 mg + naloxone 0.5, 1 and 2 mg, respectively), buprenorphine alone (2 mg), pheniramine maleate (45.5 mg) and saline at 24 hourly intervals. No significant opioid withdrawals were precipitated during any test conditions. Compared to buprenorphine alone, 4:1 BNX had comparable euphoria, drug recognition, subjective opiate sensations and drug liking (P > 0.05); 2:1 BNX condition had significantly different subjective euphoria (P = 0.001), opioid recognition (P = 0.002), subjective opioid sensations at 60 min (P = 0.027) and drug liking (P < 0.001), while 1:1 BNX had significantly different objective euphoria (P = 0.002), opioid recognition (P = 0.030), subjective opioid sensations (P < 0.001) and drug liking (P < 0.001). No significant difference was noted on sedation scores between buprenorphine alone and all three combinations of BNX. The 4:1 BNX condition did not impact the reinforcing agonist effects of buprenorphine. None of the intravenous BNX combination ratios precipitated opioid withdrawals. Findings emphasise the need for exploring more abuse deterrent mechanisms.

Comparison of the efficacy of an infusion pump or standard IV push injection to deliver naloxone in treatment of opioid toxicity

Background:The optimal goal of naloxone infusion in intensive care units is to ameliorate opioid-induced side effects in therapy or eliminate the symptoms of opioid toxicity in overdoses. Accurately monitoring and regulating the doses is critical to prevent adverse effects related to naloxone administration. The present study aimed to compare treatment outcomes when using two methods of intravenous naloxone infusion: an infusion pump or the standard method. Methods:This study involved 80 patients with signs and symptoms of opioid overdose. The patients were randomly assigned into two groups with respect to intravenous infusion of naloxone by either an infusion pump or the standard method. Results:Comparison of study parameters between the two groups at 12 and 24 hours after intervention showed significantly more compensatory acid-base imbalance in the naloxone infusion pump group. In the group that received naloxone by pump, only one patient experienced withdrawal symptoms, but withdrawal symptoms appeared in 12 patients (30.0%) in the standard intravenous infusion group within 12 hours and in seven additional patients (17.5%) within 24 hours of intervention. In the group receiving pump-based naloxone infusion therapy, no another complications were reported; however in the standard infusion group, the 12-hour and 24-hour complication rates were 55.0% and 32.5%, respectively. The length of hospital stay was 2.85±1.05 and 4.22±0.92 days for the pump and standard infusion groups, respectively (P<0.001). Conclusions:Naloxone infusion using an infusion pump may be safer with regard to hemodynamic stability, resulting in shorter hospitalization periods, and fewer posttreatment complications.

Intranasal Versus Intravenous Naloxone in Opium Poisoning in Children, A Pilot Study

Background: Opioid poisoning is a common and fatal poisoning in children in our country. Objectives: This study was designed to compare the effects of intranasal (IN) dribbling with intravenous (IV) injection of naloxone in opioid poisoning in Loghman-Hakim Hospital, Tehran, Iran. Methods: This is a prospective, clinical trial study performed on children between the ages of one to 13 years with opioid poisoning from April 2018 to April 2019 compared to IN naloxone 0.01 mg/kg dribbling versus Intravenous naloxone 0.01 mg/kg injection. Patients with nasal congestion, severe poisoning and co-ingestion were excluded. The main outcomes included GCS, response time, respiratory rate, and O2 saturation. This study was approved by the Ethics Committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.RETECH.REC.1397.258) and was registered with the Iranian Registry of Clinical Trials (www.irct.ir) (IRCT20180226038869N1). Results: A total of 44 patients (22 IV and 22 IN) with a mean age of 38.2 ± 28.8 months in IV and 36.8 ± 19.7 months in the IN naloxone group, 14 methadone and eight opium poisoning in IV and 13 methadone and nine opium poisoning in the IN group. The male/female ratio was 14/8 in both groups. There were no statistically significant differences between the two groups in RR, GCS, and O2 saturation before naloxone administration. The IV and IN groups had similar average increases in RR, O2 saturation and GCS after naloxone administration. There was a significant difference in the time of response between the two groups (P < 0.008), 3.9 ± 3 minutes in IV group and 5.9 ± 2.9 minutes in the IN group. No complications were observed in this study. Conclusions: This study showed that Intranasal naloxone is safe, effective, and a well-tolerated needleless method for opioid poisoning in children. Although the time to response was longer in the IN groups, if we add the time needed for IV catheter insertion it seems that the IN route is faster.

A patient with fever and delirium while wearing a fentanyl transdermal therapeutic system (TTS) showed marked improvement following intravenous naloxone hydrochloride administration

A patient with fever and delirium while wearing a fentanyl transdermal therapeutic system (TTS) showed marked improvement following intravenous naloxone hydrochloride administration

Pharmacokinetics and pharmacodynamics of intranasal and intravenous naloxone hydrochloride administration in healthy dogs

To evaluate the pharmacokinetics and pharmacodynamics of naloxone hydrochloride in dogs following intranasal (IN) and IV administration. 6 healthy adult mixed-breed dogs. In a blinded crossover design involving 2 experimental periods separated by a washout period (minimum of 7 days), dogs were randomly assigned to receive naloxone IN (4 mg via a commercially available fixed-dose naloxone atomizer; mean ± SD dose, 0.17 ± 0.02 mg/kg) or IV (0.04 mg/kg) in the first period and then the opposite treatment in the second period. Plasma naloxone concentrations, dog behavior, heart rate, and respiratory rate were evaluated for 24 hours/period. Naloxone administered IN was well absorbed after a short lag time (mean ± SD, 2.3 ± 1.4 minutes). Mean maximum plasma concentration following IN and IV administration was 9.3 ± 2.5 ng/mL and 18.8 ± 3.9 ng/mL, respectively. Mean time to maximum concentration following IN administration was 22.5 ± 8.2 minutes. Mean terminal half-life after IN and IV administration was 47.4 ± 6.7 minutes and 37.0 ± 6.7 minutes, respectively. Mean bioavailability of naloxone administered IN was 32 ± 13%. There were no notable changes in dog behavior, heart rate, or respiratory rate following naloxone administration by either route. Use of a naloxone atomizer for IN naloxone administration in dogs may represent an effective alternative to IV administration in emergency situations involving opioid exposure. Future studies are needed to evaluate the efficacy of IN naloxone administration in dogs with opioid intoxication, including a determination of effective doses.

A Randomized Cross-Over Trial Comparing the Effect of Intramuscular Versus Intranasal Naloxone Reversal of Intravenous Fentanyl on Odor Detection in Working Dogs.

Simple SummaryThe recent increase in fentanyl as an illicit street drug, paired with its powerful potency, has led to emergency personnel carrying naloxone, an opioid reversal agent, for the case of accidental exposures and overdoses in humans. Canine officers, if demonstrating intoxication from exposure to fentanyl, are consequently administered naloxone, however the effects of this treatment on the dogs’ scent detection are unknown. We tested the effects of intravenous and intranasal naloxone administration on dogs’ scent detection 2, 24, and 48 h after intravenous fentanyl sedation and naloxone reversal. We found no detectable influence of this fentanyl sedation and naloxone reversal on dogs’ abilities, regardless of whether they received intranasal or intramuscular naloxone. Results suggest there is no evidence that under these conditions, intravenous fentanyl followed by naloxone reversal impairs canine olfactory ability.Fentanyl is a potent opioid used clinically as a pain medication and anesthetic but has recently seen a sharp rise as an illicit street drug. The potency of fentanyl means mucous membrane exposure to a small amount of the drug can expose first responders, including working canines, to accidental overdose. Naloxone, a fast-acting opioid antagonist administered intranasally (IN) or intramuscularly (IM) is currently carried by emergency personnel in the case of accidental exposure in both humans and canines. Despite the fact that law enforcement relies heavily on the olfactory abilities of canine officers, the effects of fentanyl exposure and subsequent reversal by naloxone on the olfactory performance of canines are unknown. In a block-randomized, crossover trial, we tested the effects of IN and IM naloxone on the abilities of working dogs to recognize the odor of Universal Detection Calibrant (UDC) prior to, and two, 24, and 48 h after intravenous fentanyl sedation and naloxone reversal. No detectable influence of fentanyl sedation and naloxone reversal on the dogs’ olfactory abilities was detected. We also found no difference in olfactory abilities when dogs received IN or IM naloxone. Together, results suggest no evidence that exposure to intravenous fentanyl followed by naloxone reversal impairs canine olfactory ability under these conditions.

Tools for Community-Based Pharmacist Patient Care Services to Support Optimal Opioid Use

Tools for Community-Based Pharmacist Patient Care Services to Support Optimal Opioid Use

(357) Effect of Naloxone on Touch Intensity and Pleasantness

Both light skin stroking (engaging the C-tactile afferent sensory pathway) and deep pressure touch (as in deep tissue massage) are commonly perceived as pleasant and relaxing. Opioid blockade has been found to increase receipt of grooming in monkeys, suggesting possible opioid modulation of touch pleasantness. Recently, human data [1] suggested that blocking opioid receptors might decrease the perceived intensity of gentle brushing but increase its pleasantness. The current study examined the role of endogenous opioids in the perceived intensity and pleasantness of pleasant touch. Using a double-blind cross-over design, 24 healthy adult participants received intravenous naloxone or saline (control) on separate days. Blocks of gentle brushing and deep pressure compression were administered on the lower left calf. Participants rated the intensity and pleasantness of each stimulus, as well as current mood and anxiety. Naloxone significantly reduced perceived intensity of gentle brushing (p = 0.039), but did not affect brushing pleasantness (p = 0.44) or intensity or pleasantness of deep pressure (p = 0.97; p = 0.85). The naloxone-induced reduction in gentle touch intensity replicates results previously seen in chronic pain patients [1]. The lack of effect on pleasantness in this study versus [1] could relate to differences in the location of touch (arm or leg), sex of the experimenters, or whether the touch followed pain tasks. However, in the current study, naloxone was marginally anxiolytic (p = 0.07), and naloxone-induced changes in touch pleasantness were significantly more correlated with subsequent mood and anxiety ratings than were changes during saline (mood p = 0.04; anxiety p

The association between endogenous opioid function and morphine responsiveness: a moderating role for endocannabinoids.

We sought to replicate previous findings that low endogenous opioid (EO) function predicts greater morphine analgesia and extended these findings by examining whether circulating endocannabinoids and related lipids moderate EO-related predictive effects. Individuals with chronic low-back pain (n = 46) provided blood samples for endocannabinoid analyses, then underwent separate identical laboratory sessions under 3 drug conditions: saline placebo, intravenous (i.v.) naloxone (opioid antagonist; 12-mg total), and i.v. morphine (0.09-mg/kg total). During each session, participants rated low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects 4 times in sequence after incremental drug dosing. Mean morphine effects (morphine-placebo difference) and opioid blockade effects (naloxone-placebo difference; to index EO function) for each primary outcome (low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects) were derived by averaging across the 4 incremental doses. The association between EO function and morphine-induced back pain relief was significantly moderated by endocannabinoids [2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)]. Lower EO function predicted greater morphine analgesia only for those with relatively lower endocannabinoids. Endocannabinoids also significantly moderated EO effects on morphine-related changes in visual analog scale-evoked pain intensity (2-AG), drug liking (AEA and 2-AG), and desire to take again (AEA and 2-AG). In the absence of significant interactions, lower EO function predicted significantly greater morphine analgesia (as in past work) and euphoria. Results indicate that EO effects on analgesic and subjective responses to opioid medications are greatest when endocannabinoid levels are low. These findings may help guide development of mechanism-based predictors for personalized pain medicine algorithms.

Effects of intranasal and intravenous naloxone hydrochloride on heart rate and respiratory rate in dogs

Introduction: The objective of this study was to determine the effects of 4 mg intranasal (IN) and 0.04 mg kg−1 intravenous (IV) naloxone HCl on heart rate and respiratory rate in dogs.

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Background: Buprenorphine is a partial opioid agonist with a reported “ceiling effect” for respiratory depression. Despite implied safety, it has been associated with significant overdoses. Conflicting data exist regarding the response to naloxone. Research Question: How do the clinical characteristics and response to naloxone following buprenorphine overdose compare with those of heroin and methadone overdose? Methods: Consecutive patients admitted to two teaching hospitals with Glasgow Coma Score (GCS) <12 and at least two of the following three criteria were included in this 4year prospective. Observational Study: History suggestive of opioid overdose, pinpoint pupils, or initial respiratory rate <12/min. Demographics, intent, initial GCS, respiratory rate, oxygen saturation (SpO2), and vital signs were collected. Urine toxicological screening was performed and only overdoses involving the exclusive presence of 6-monoacetylmorphine, buprenorphine, or methadone were included. Cases involving multiple opioids were excluded, but cases with benzodiazepine coingestion were allowed. Patients were treated with naloxone and/or flumazenil. Antidote dose and order were at the discretion of the attending physician. Response to naloxone was considered “positive” if full awakening occurred or intubation avoided. Results: During the study, 160 patients were admitted for opioid overdose and 84 met inclusion criteria. These 84 were divided into three groups: heroin (n=26), buprenorphine (n=39), and methadone (n=19). Initial GCS, respiratory rate, SpO2, and blood gas analysis were similar between groups. Benzodiazepine coingestion was more common in the buprenorphine vs heroin group and suicide more common in the methadone vs buprenorphine group. Naloxone was administered in 65% of 84 patients. Buprenorphine-poisoned patients did not respond to 0.4– 0.8 mg intravenous naloxone (0/19). Conclusion: Buprenorphine overdose induced a typical opioid syndrome that was not reversed with naloxone. Critique: The strength of the study was a large number of patients and confirmation of toxins. Weaknesses include lack of data on pinpoint pupils (an inclusion criteria), subjective endpoints, preponderance of benzodiazepine co-ingestions, and lack of detailed naloxone dosing information. Implication for Toxicologists: This study gives further evidence that buprenorphine overdose produces a typical opioid toxidrome. If naloxone is used to treat suspected buprenorphine overdose, doses of 0.4 to 0.8 mg may be insufficient to reverse the clinical effects. Benzodiazepines are common coingestants.

Comparative Study between Naloxone as an Additive to Lidocaine and Naloxone Infusion in Intravenous Regional Anaesthesia for Short Procedures of Upper Limb Surgeries

Background: intravenous regional anesthesia (IVRA) was first described by August Bier in 1908. IVRA is an anesthetic technique for surgical procedures on the body's extremities where a local anesthetic is injected intravenously. The local anesthetic diffuses from the peripheral vascular bed to nonvascular tissue such as axons and nerve endings. Objective: The aim of the present study was to compare the effect of adding ultra-low dose of naloxone to lidocaine for IVRA and the effect of using intravenous naloxone infusion with IVRA for elective short procedures in the upper limb. Patients and Methods: This is Prospective; randomized, controlled, multicenter, double blind study that done in Alazhar University hospitals. Each group contains 30 patients. The lidocaine in the study is 2% 3mg/kg in all groups. In all groups 0.9% NaCl is added to make up a total volume of 30 ml. Results: The result of our study showed that local intravenous adjuvant naloxone (100 or 50ng) with lidocaine 1 % shortens the onset of blocks and prolongs the recovery from anesthesia. Moreover, it reduces the amount of opioids consumption and intraoperative pain score in patient undergoing short upper limb surgeries. Conclusion: Naloxone IV infusion not improves the analgesic effect of intravenous anesthesia or prolongs the recovery from anesthesia. Regarding safety, adjuvant naloxone appears to be safe with no recorded side effects.

Comparative Study between Naloxone as an Additive to Lidocaine and Naloxone Infusion in Intravenous Regional Anaesthesia for Short Procedures of Upper Limb Surgeries

Background: intravenous regional anesthesia (IVRA) was first described by August Bier in 1908. IVRA is an anesthetic technique for surgical procedures on the body's extremities where a local anesthetic is injected intravenously. The local anesthetic diffuses from the peripheral vascular bed to nonvascular tissue such as axons and nerve endings. Objective: The aim of the present study was to compare the effect of adding ultra-low dose of naloxone to lidocaine for IVRA and the effect of using intravenous naloxone infusion with IVRA for elective short procedures in the upper limb. Patients and Methods: This is Prospective; randomized, controlled, multicenter, double blind study that done in Alazhar University hospitals. Each group contains 30 patients. The lidocaine in the study is 2% 3mg/kg in all groups. In all groups 0.9% NaCl is added to make up a total volume of 30 ml. Results: The result of our study showed that local intravenous adjuvant naloxone (100 or 50ng) with lidocaine 1 % shortens the onset of blocks and prolongs the recovery from anesthesia. Moreover, it reduces the amount of opioids consumption and intraoperative pain score in patient undergoing short upper limb surgeries. Conclusion: Naloxone IV infusion not improves the analgesic effect of intravenous anesthesia or prolongs the recovery from anesthesia. Regarding safety, adjuvant naloxone appears to be safe with no recorded side effects.