Presenting Data versus  Predictions as Basic Scientific Information: Target-controlled Infusions versus  Microgram per Kilogram per Minutes

Avram, Michael J.

doi:10.1097/aln.0b013e3182096b8e

Cited by 5 publications

(3 citation statements)

References 10 publications

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“…This illustrates the importance of measuring actual drug concentrations when performing drugresponse studies. 25 Measured remifentanil concentrations were higher and more variable in patients with obstructive sleep apnea. It is not immediately apparent why.…”

Section: Discussionmentioning

confidence: 97%

“…30 The relevant consideration is that discordance between expected versus measured remifentanil concentrations again illustrates the importance of measuring actual drug concentrations when performing drug-response studies, lest observed clinical differences be misattributed as pharmacodynamic differences. 25 There are several possible explanations for why no difference was seen in remifentanil-induced miosis between obstructive sleep apnea and non-obstructive sleep apnea patients. Previous studies that suggest a difference in opioid sensitivity between children with and without obstructive sleep apnea have assumed similar pharmacokinetics without measuring actual opioid plasma concentrations.…”

Section: Discussionmentioning

confidence: 99%

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Opioid Sensitivity in Children with and without Obstructive Sleep Apnea

et al. 2019

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C hildhood obstructive sleep apnea, defined by periodic, partial or complete obstruction of the upper airway during sleep, is a common disorder in pediatric patients, with a prevalence as high as 5.7%. 1,2 Children with obstructive sleep apnea often present for surgery and other procedures that require general anesthesia. In fact, the treatment of obstructive sleep apnea is the primary indication for more than 75% of children undergoing tonsillectomy with or without adenoidectomy. 3 Tonsillectomy is the most common pediatric operation performed in the United States, with more than 500,000 tonsillectomies performed annually. 4 Unfortunately, children at high risk for obstructive sleep apnea are three times more likely to have posttonsillectomy respiratory complications and apneic adverse events than children at low risk for obstructive sleep apnea, 5,6 and the rate of complications in patients with obstructive sleep apnea posttonsillectomy (16 to 27%) is substantially increased compared to that of the general pediatric postoperative population (0 to 1.3%). 7-11 These complications include oxygen desaturation, hypercapnia, obstructive apneas requiring continuous positive airway pressure or airway instrumentation, unexpected intensive care unit admission, and in rare cases, death. Concerns for a heightened risk of opioid induced respiratory depression make the perioperative use of opioids in children with obstructive sleep apnea particularly challenging, if not controversial. It has been suggested that they may be at risk from overdose if administered what would otherwise be considered a normal dose of opioid. 6 Indeed, some pediatric surgical centers automatically reduce by half aBStract Background: Opioids are a mainstay of perioperative analgesia. Opioid use in children with obstructive sleep apnea is challenging because of assumptions for increased opioid sensitivity and assumed risk for opioid-induced respiratory depression compared to children without obstructive sleep apnea. These assumptions have not been rigorously tested. This investigation tested the hypothesis that children with obstructive sleep apnea have an increased pharmacodynamic sensitivity to the miotic and respiratory depressant effects of the prototypic μ-opioid agonist remifentanil. Methods: Children (8 to 14 yr) with or without obstructive sleep apnea were administered a 15-min, fixed-rate remifentanil infusion (0.05, 0.1, or 0.15 μg • kg-1 • min-1). Each dose group had five patients with and five without obstructive sleep apnea. Plasma remifentanil concentrations were measured by tandem liquid chromatography mass spectrometry. Remifentanil effects were measured via miosis, respiratory rate, and end-expired carbon dioxide. Remifentanil pharmacodynamics (miosis vs. plasma concentration) were compared in children with or without obstructive sleep apnea. results: Remifentanil administration resulted in miosis in both nonobstructive sleep apnea and obstructive sleep apnea patients. No differences in the relationship between remifentanil concentra...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Opioid Sensitivity in Children with and without Obstructive Sleep Apnea

et al. 2019

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“…In addition, studies often use predicted or modeled drug concentrations, but it is important to use actual measured drug concentrations, such as to confirm adequacy of dosing or in pharmacokinetic and/or pharmacodynamics modeling. 41…”

Section: Discussionmentioning

confidence: 99%

Morphine and Hydromorphone Effects, Side Effects, and Variability: A Crossover Study in Human Volunteers

et al. 2023

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Background Balancing between opioid analgesia and respiratory depression continues to challenge clinicians in perioperative, emergency department and other acute care settings. Morphine and hydromorphone are postoperative analgesic standards. Nevertheless, their comparative effects and side effects, timing, and respective variabilities, remain poorly understood. We tested the hypothesis that intravenous morphine and hydromorphone differ in onset, magnitude, duration and variability of analgesic and ventilatory effects. Methods We conducted a randomized crossover study in healthy volunteers. Forty-two subjects received a 2-hour intravenous infusion of hydromorphone (0.05 mg/kg) or morphine (0.2 mg/kg) 1-2 weeks apart. We measured arterial opioid concentrations, analgesia in response to heat pain (maximally tolerated temperature, and verbal analog pain scores at discreet preset temperatures to determine half-maximum temperature effect), dark-adapted pupil diameter and miosis, end-expired CO2, and respiratory rate for 12 h after dosing. Results For morphine and hydromorphone, respectively: maximum miosis was less (3.9 [3.4,4.2] vs 4.6 mm [4.0,5.0], P<0.001; median and 25%-75% quantiles) and occurred later (3.1 ± 0.9 vs 2.3 ± 0.7 h after infusion start, P<0.001; mean ± SD); maximum tolerated temperature was less (49 ± 2 vs 50 ± 2°C, P<0.001); verbal pain scores at end-infusion at the most informative stimulus (48.2°C) were 82 ± 4 and 59 ± 3 (P<0.001); maximum end-expired CO2 was 47 [45,50] and 48 mmHg [46,51] (P=0.007), and occurred later (5.5 ± 2.8 vs 3.0 ± 1.5 h after infusion start, P<0.001); respiratory nadir was 9 ± 1 and 11 ± 2 breaths/min (P<0.001) and occurred at similar times. Area under the temperature tolerance-time curve was less for morphine (1.8 [0.0,4.4]) than hydromorphone (5.4°C-h [1.6,12.1] P<0.001). Inter-individual variability in clinical effects did not differ between opioids. Conclusions For morphine compared to hydromorphone, analgesia and analgesia relative to respiratory depression were less, onset of miosis and respiratory depression was later, and duration of respiratory depression was longer. For each opioid, timing of the various clinical effects was not coincident. Results may enable more rational opioid selection, and suggest hydromorphone may have a better clinical profile.

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