The Antagonism of Morphine Anesthesia by Naloxone

Hasbrouck, Jan D.

doi:10.1097/00132586-197210000-00031

Cited by 3 publications

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“…One of the initial studies of parenteral naloxone dosing in a clinical setting found that all patients who had received high doses of IV morphine (up to 6 mg/kg) as the sole anesthetic for cardiac surgery experienced reversal of post-operative respiratory depression following 10 μg/kg of naloxone IV administered in divided doses of 5 μg/kg. 88 Additional studies in anesthetized patients have also reported 5 μg/kg IV to be an adequate dose to protect against or reverse opioid-induced respiratory depression measured as both respiratory rate and minute volume; however, this dose often needs to be repeated or followed by an infusion of naloxone to maintain this effect. 7,88,89…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

“…88 Additional studies in anesthetized patients have also reported 5 μg/kg IV to be an adequate dose to protect against or reverse opioid-induced respiratory depression measured as both respiratory rate and minute volume; however, this dose often needs to be repeated or followed by an infusion of naloxone to maintain this effect. 7,88,89…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

“…118 Surgical patients receiving high-dose morphine required additional doses of IV naloxone anywhere from 30 min to 90 min after initial reversal. 88,89 There are reports that combining IV and IM administration of naloxone extends the duration of effect, 89,119 but the larger doses administered may precipitate opioid-withdrawal symptoms and may not confer a survival benefit following opioid overdose. 120…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

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Naloxone dosage for opioid reversal: current evidence and clinical implications

Lynn

Galinkin

2017

Therapeutic Advances in Drug Safety

251

196

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Current contextOpioid overdoses have quadrupled in the past 15 years, and in 2015 there were over 33,000 opioidrelated deaths in the United States. 1 Opioid overdose induces respiratory depression that can lead to hypoxia, hypercarbia and death. In an attempt to expedite treatment and improve outcomes following overdose, naloxone is increasingly being utilized in a pre-hospital setting by both emergency personnel and prescribed to laypersons for out-of-hospital administration. 2 Efficacy of reversal following naloxone administration by laypersons is high, having been reported at 75-100%, 3 and in general take-home naloxone programs are considered effective for reducing opioid-overdose mortality. 4 Naloxone overall is a safe medication, and is not known to cause harm when administered in typical doses to opioid-naïve patients. [5][6][7][8] There is concern about the precipitation of opioid-withdrawal syndrome following its administration in the setting of prior opioid exposure. Despite the long-standing use of naloxone to reverse the symptoms of opioid overdose or toxicity, appropriate dosing remains controversial, with varying doses recommended over time and by medical specialty. 9 In a hospital setting, this medication is typically administered initially in a low dose, which is then titrated to optimize reversal of opioid-induced respiratory depression while attempting to minimize the risk of withdrawal. 10 In a non-medical setting, the ideal of gradually titrating naloxone to effect is not practical, thus a single standardized initial dose for out-of-hospital naloxone rescue has been sought. This review will evaluate the literature to address the question of optimal naloxone dosing to reverse opioidinduced respiratory depression while minimizing patient risk. HistoryNaloxone was developed in the early 1960s as a novel opioid antagonist with fewer side effects than its predecessors. 11 Naloxone hydrochloride is a competitive mu-opioid receptor antagonist historically used only by trained clinical professionals for the reversal of opioid overdose in an emergency or inpatient setting. It is approved for administration by a variety of routes, including intravenous (IV), intramuscular (IM), subcutaneous (SQ) and intranasal (IN), but is also administered via inhalation following nebulization or endotracheal tube in intubated patients. [12][13][14] Formulations for many other routes of administration are currently under development, including sublingual and buccal. 15 Naloxone is not typically administered orally due Naloxone dosage for opioid reversal: current evidence and clinical implications Rachael Rzasa Lynn and JL Galinkin Abstract: Opioid-related mortality is a growing problem in the United States, and in 2015 there were over 33,000 opioid-related deaths. To combat this mortality trend, naloxone is increasingly being utilized in a pre-hospital setting by emergency personnel and prescribed to laypersons for out-of-hospital administration. With increased utilization of naloxone there has been a subsequent reduc...

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Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

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Naloxone dosage for opioid reversal: current evidence and clinical implications

Lynn

Galinkin

2017

Therapeutic Advances in Drug Safety

251

196

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“…The reversal of narcotic intoxications and obstetric analgesia by naloxone has recently been well documented in the literature. The use of naloxone after morphine anaesthesia has also been studied ( HASBROUCK 1971, LONGNECKER et al 1973, JOHNSTONE et al 1974). As shorter-acting narcotic analgesics are frequently used for supplementation of combined anaesthesia, this study was undertaken in order to investigate dose relationships between different doses of naloxone and fentanyl, our primary intraoperative analgesic.…”

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confidence: 99%

Antagonism of Fentanyl with Naloxone during N₂O+O₂+ Halothane Anaesthesia

Tigerstedt

1977

Acta Anaesthesiol Scand

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To investigate the antagonistic effect of naloxone on fentanyl-induced respiratory depression, 55 patients (randomly divided into various study and control groups were studied during nitrous-oxide-oxygen-halothane anaesthesia. Respiratory depression after 0.1 mg of fentanyl was totally reversed by 10 microgram/kg of naloxone, measured as 100% restoration of spontaneous respiration, normal minute volume and end-tidal CO2, while 15 microgram/kg of naloxone was needed to antagonize 0.2 mg of fentanyl. The respective control groups remained apnoeic. If no fentanyl had previously been administered, there was no difference in the respiratory behaviour of naloxone-treated and control patients, which indicates that no unspecific analeptic effect of naloxone could be demonstrated. The circulatory changes after fentanyl were nearly reversed by naloxone, as has been found earlier with other narcotics. Recovery from anaesthesia was scored from 0 to 10 (using a modification of Apgar scores for newborns), and somewhat higher mean scores were obtained with the naloxone-treated patients than with their controls. However, higher postoperative pain scores were recorded in these patients as well as a higher incidence of nausea and vomiting. The study demonstrates the dose-relationships of fetanyl and naloxone for estimation of total antagonism; however, the use of naloxone for partial antagonism at the termination of anaesthesia cannot be based on these findings.

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“…Numerous publications during the last few years have demonstrated the superiority of naloxone as the drug of choice for narcotic antagonism, especially in the management of narcotic poisoning and in the problems arising in the use of narcotics in obstetric analgesia. In anaesthesiology, the main interest has been concentrated on studies on the reversal of morphine anaesthesia ( HASBROUCK 1971, LONCNECKER et al 1973, JOHNSTONE et al 1974 or other long-acting narcotics (FOLDES et a]. 1969), where a safe and specific antagonist is of obvious benefit.…”

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confidence: 99%

Naloxone as Narcotic Antagonist after Balanced Anaesthesia

Tigerstedt¹

1977

Acta Anaesthesiol Scand

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Different modes of naloxone administration were studied in 100 patients following N2O-O2-relaxant anaesthesia, where fentanyl was administered for analgesia according to a standardized dose schedule (mean 4.3 microgram/kg/h). After reversal of muscular relaxation, the patients were randomly given naloxone--either 1.0 or 2.5 microgram/kg i.v. or 2.5 or 5.0 microgram/kg i.m., or none (control). Each group consisted of 20 patients. Awakening was fastest after 2.5 microgram/kg i.v. of naloxone (1.8 +/- 0.1 min), the time being significantly shorter (P less than 0.025) than in the control group (2.7 +/- 0.4 min). After 15 min, the minute volume and frequency of respiration were significantly higher (P less than 0.05) in all naloxone groups than in the control group. However, the arterialized venous PCO2 did not show significant differences during the recovery. It is therefore suggested that naloxone reversal may cause an increase in CO2 production. The immediate postoperative pain (score 0-3) was mildest in the control group (1.0 mean) and severest after 2.5 microgram/kg i.v. of naloxone (1.8 mean); the difference was statistically significant (P less than 0.05). The groups receiving 1.0 microgram/kg i.v. and 2.5 microgram/kg i.m. did not differ from each other (1.2 mean). Nausea and vomiting were reported more often after 5.0 microgram/kg im. of naloxone than in other groups. After moderate doses of fentanyl during balanced anaesthesia, routine use of naloxone does not seem to be necessary, but if rapid recovery is essential, 1.0 microgram/kg i.v. or 2.5 microgram/kg i.m. of naloxone may be recommended and these doses do not cause a higher incidence of side effects.

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The Antagonism of Morphine Anesthesia by Naloxone

Cited by 3 publications

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Naloxone dosage for opioid reversal: current evidence and clinical implications

Naloxone dosage for opioid reversal: current evidence and clinical implications

Antagonism of Fentanyl with Naloxone during N₂O+O₂+ Halothane Anaesthesia

Naloxone as Narcotic Antagonist after Balanced Anaesthesia

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The Antagonism of Morphine Anesthesia by Naloxone

Cited by 3 publications

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Naloxone dosage for opioid reversal: current evidence and clinical implications

Naloxone dosage for opioid reversal: current evidence and clinical implications

Antagonism of Fentanyl with Naloxone during N2O+O2+ Halothane Anaesthesia

Naloxone as Narcotic Antagonist after Balanced Anaesthesia

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Antagonism of Fentanyl with Naloxone during N₂O+O₂+ Halothane Anaesthesia