{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:30:45Z","timestamp":1772155845970,"version":"3.50.1"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Anesthesiology"],"published-print":{"date-parts":[[2010,6,1]]},"abstract":"\n Background<\/jats:title>\n Few studies address the dynamic effect of opioids on respiration. Models with intact feedback control of carbon dioxide on ventilation (non-steady-state models) that correctly incorporate the complex interaction among drug concentration, end-tidal partial pressure of carbon dioxide concentration, and ventilation yield reliable descriptions and predictions of the behavior of opioids. The authors measured the effect of remifentanil on respiration and developed a model of remifentanil-induced respiratory depression.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Ten male healthy volunteers received remifentanil infusions with different infusion speeds (target concentrations: 4-9 ng\/ml; at infusion rates: 0.17-9 ng x ml x min) while awake and at the background of low-dose propofol. The data were analyzed with a nonlinear model consisting of two additive linear parts, one describing the depressant effect of remifentanil and the other describing the stimulatory effect of carbon dioxide on ventilation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The model adequately described the data including the occurrence of apnea. Most important model parameters were as follows: C50 for respiratory depression 1.6 +\/- 0.03 ng\/ml, gain of the respiratory controller (G) 0.42 - 0.1 l x min x Torr, and remifentanil blood effect site equilibration half-life (t(1\/2)ke0) 0.53 +\/- 0.2 min. Propofol caused a 20-50% reduction of C50 and G but had no effect on t(1\/2)ke0. Apnea occurred during propofol infusion only. A simulation study revealed an increase in apnea duration at infusion speeds of 2.5-0.5 ng x ml x min followed by a reduction. At an infusion speed of < or = 0.31 ng x ml x min, no apnea was seen.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The effect of varying remifentanil infusions with and without a background of low-dose propofol on ventilation and end-tidal partial pressure of carbon dioxide concentration was described successfully using a non-steady-state model of the ventilatory control system. The model allows meaningful simulations and predictions.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/aln.0b013e3181d69087","type":"journal-article","created":{"date-parts":[[2010,5,11]],"date-time":"2010-05-11T02:41:51Z","timestamp":1273545711000},"page":"1382-1395","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":54,"title":["Modeling the Non\u2013Steady State Respiratory Effects of Remifentanil in Awake and Propofol-sedated Healthy Volunteers"],"prefix":"10.1097","volume":"112","author":[{"given":"Erik","family":"Olofsen","sequence":"first","affiliation":[{"name":"Research Associate."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merel","family":"Boom","sequence":"additional","affiliation":[{"name":"Ph.D. Student."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diederik","family":"Nieuwenhuijs","sequence":"additional","affiliation":[{"name":"Resident, Department of Anesthesiology, Leiden University Medical Center. Current position: Staff Anesthesiologist, St. Antonius Ziekenhuis, Nieuwegein, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise","family":"Sarton","sequence":"additional","affiliation":[{"name":"Staff Anesthesiologist."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Teppema","sequence":"additional","affiliation":[{"name":"Associate Professor."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon","family":"Aarts","sequence":"additional","affiliation":[{"name":"Professor, Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Dahan","sequence":"additional","affiliation":[{"name":"Professor, Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-18-20251013"},{"key":"R2-18-20251013"},{"key":"R3-18-20251013"},{"key":"R4-18-20251013"},{"key":"R5-18-20251013"},{"key":"R6-18-20251013"},{"key":"R7-18-20251013"},{"key":"R8-18-20251013"},{"key":"R9-18-20251013"},{"key":"R10-18-20251013"},{"key":"R11-18-20251013"},{"key":"R12-18-20251013"},{"key":"R13-18-20251013"},{"key":"R15-18-20251013"},{"key":"R16-18-20251013"},{"key":"R17-18-20251013"},{"key":"R20-18-20251013"},{"key":"R21-18-20251013"},{"key":"R22-18-20251013"},{"key":"R23-18-20251013"},{"key":"R24-18-20251013"},{"key":"R25-18-20251013"},{"key":"R26-18-20251013"},{"key":"R27-18-20251013"},{"key":"R28-18-20251013"},{"key":"R29-18-20251013"}],"container-title":["Anesthesiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/pubs.asahq.org\/anesthesiology\/article-pdf\/112\/6\/1382\/251666\/0000542-201006000-00018.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.lww.com\/00000542-201006000-00016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T16:08:50Z","timestamp":1760371730000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00000542-201006000-00016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,1]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010]]}},"URL":"https:\/\/doi.org\/10.1097\/aln.0b013e3181d69087","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.3538956.3238054","asserted-by":"object"}]},"ISSN":["0003-3022"],"issn-type":[{"value":"0003-3022","type":"print"}],"subject":[],"published":{"date-parts":[[2010,6,1]]}}}