Effect of Combining Ultralow-dose Naloxone with Morphine in Intravenous Patient-controlled Analgesia: The Cut-off Ratio of Naloxone to Morphine for Antiemesis After Gynecologic Surgery

Yeh, Yu-Chang; Lin, Tzu-Fu; Wang, Chen-Hua; Wang, Yongping; Lin, Chun-Chih; Sun, Wei‐Zen

doi:10.1016/s0929-6646(08)60156-4

Cited by 14 publications

(21 citation statements)

References 17 publications

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“…14–16 Although the use of a continuous basal opioid infusion is not universal in pediatric pain management, it is more frequently used 2,14,17 than in adult practice. 1,8,9,12,16 Our findings that a higher naloxone infusion rate more effectively reduced pruritus in children receiving basal/bolus IV PCA than the lower doses reported to be effective in adult patients receiving bolus-only PCA are similar to those reported in a small pilot study of patients with sickle cell anemia who received morphine via continuous infusion in combination with naloxone. 18 …”

Section: Discussionsupporting

confidence: 82%

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The Optimal Dose of Prophylactic Intravenous Naloxone in Ameliorating Opioid-Induced Side Effects in Children Receiving Intravenous Patient-Controlled Analgesia Morphine for Moderate to Severe Pain

Monitto¹,

Kost‐Byerly²,

White³

et al. 2011

Anesthesia &Amp; Analgesia

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BACKGROUND Opioid-induced side effects, such as pruritus, nausea, and vomiting are common and may be more debilitating than pain itself. A continuous low-dose naloxone infusion (0.25 µg/kg/h) ameliorates some of these side effects in many but not all patients without adversely affecting analgesia. We sought to determine the optimal dose of naloxone required to minimize opioid-induced side effects and to measure plasma morphine and naloxone levels in a dose escalation study. METHODS Fifty-nine pediatric patients (24 male/35 female; average age 14.2 ± 2.2 years) experiencing moderate to severe postoperative pain were started on IV patient-controlled analgesia morphine (basal infusion 20 µg/kg/h, demand dose 20 µg/kg, 5 doses/h) and a low-dose naloxone infusion (initial cohort: 0.05 µg/kg/h; subsequent cohorts: 0.10, 0.15, 0.25, 0.40, 0.65, 1, and 1.65 µg/kg/h). If 2 patients developed intolerable nausea, vomiting, or pruritus, the naloxone infusion was increased for subsequent patients. Dose/treatment success occurred when 10 patients had minimal side effects at a naloxone dose. Blood samples were obtained for measurement of plasma morphine and naloxone levels after initiation of the naloxone infusion, processed, stored, and measured by tandem mass spectrometry with electrospray positive ionization. RESULTS The minimum naloxone dose at which patients were successfully treated with a <10% side effect/failure rate was 1 µg/kg/h; cohort size varied between 4 and 11 patients. Naloxone was more effective in preventing pruritus than nausea and vomiting. Concomitant use of supplemental medicines to treat opioid-induced side effects was required at all naloxone infusion rates. Plasma naloxone levels were below the level of assay quantification (0.1 ng/mL) for infusion rates ≤0.15 µg/kg/h. At rates >0.25 µg/kg/h, plasma levels increased linearly with increasing infusion rate. In each dose cohort, patients who failed therapy had comparable or higher plasma naloxone levels than those levels measured in patients who did not fail treatment. Plasma morphine levels ranged between 3.52 and 172 ng/mL, and >90% of levels ranged between 10.2 and 61.6 ng/mL. Plasma morphine levels were comparable between patients who failed therapy and those patients who achieved symptom control. CONCLUSIONS Naloxone infusion rates ≥1 µg/kg/h significantly reduced, but did not eliminate, the incidence of opioid-induced side effects in postoperative pediatric patients receiving IV patient-controlled analgesia morphine. Patients who failed therapy generally had plasma naloxone and morphine levels that were comparable to those who had good symptom relief suggesting that success or failure to ameliorate opioid-induced side effects was unrelated to plasma levels.

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Section: Discussionsupporting

confidence: 82%

“…8,9,12 Although we also found side effect amelioration at lower doses in our study, higher doses (≥1 µg/kg/h) were more consistently effective. A possible explanation for these different results may simply be related to how IV PCA was provided in this study.…”

Section: Discussionsupporting

confidence: 52%

The Optimal Dose of Prophylactic Intravenous Naloxone in Ameliorating Opioid-Induced Side Effects in Children Receiving Intravenous Patient-Controlled Analgesia Morphine for Moderate to Severe Pain

Monitto¹,

Kost‐Byerly²,

White³

et al. 2011

Anesthesia &Amp; Analgesia

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“…Three of nine studies recorded postoperative antiemetic medication doses and found statistically significant decreases among patients receiving naloxone (RR 0.64 #bib95% CI 0.42–0.96, p=0.03; Figure ) . However, reduction in antiemetic dosing needs and PONV among patients receiving naloxone should be interpreted with caution based on limited patient documentation (n=186) relative to the total patient pool (n=946).…”

Section: Resultsmentioning

confidence: 99%

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

Barrons

Woods

2017

Pharmacotherapy

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“…11 Studies of naloxone-opioid PCA admixtures in adult patients have reported varying results, including poorer quality of analgesia, 12 no benefit, 13 or improved side effects with unchanged pain and opioid requirements. 14,15 Clearly, reducing adverse effects without compromising the quality of analgesia or increasing opioid consumption requires careful selection of the relative doses of naloxone and morphine. A dose-finding study in children showed that naloxone 1 lgÁkg -1 Áhr -1 was the minimum dose at which participants were successfully treated for OIP with a \ 10% failure rate and that 1.65 lgÁkg -1 Áhr -1 was as effective without increasing opioid requirements.…”

Section: Résumémentioning

confidence: 99%

A naloxone admixture to prevent opioid-induced pruritus in children: a randomized controlled trial

West

Ansermino

Carr

et al. 2015

Can J Anesth/J Can Anesth

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Effect of Combining Ultralow-dose Naloxone with Morphine in Intravenous Patient-controlled Analgesia: The Cut-off Ratio of Naloxone to Morphine for Antiemesis After Gynecologic Surgery

Abstract: The antiemetic efficacy of ultralow-dose naloxone combined with PCA morphine is limited by a cut-off ratio of naloxone to morphine of 1:10,000.

Cited by 14 publications

References 17 publications

The Optimal Dose of Prophylactic Intravenous Naloxone in Ameliorating Opioid-Induced Side Effects in Children Receiving Intravenous Patient-Controlled Analgesia Morphine for Moderate to Severe Pain

The Optimal Dose of Prophylactic Intravenous Naloxone in Ameliorating Opioid-Induced Side Effects in Children Receiving Intravenous Patient-Controlled Analgesia Morphine for Moderate to Severe Pain

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

A naloxone admixture to prevent opioid-induced pruritus in children: a randomized controlled trial

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