Selective phosphodiesterase 5 inhibition does not reduce propofol sedation requirements but affects speed of recovery and plasma cyclic guanosine 3 ',5 '-monophosphate concentrations in healthy volunteers

T Engelhardt, J MacDonald, H F Galley, N R Webster

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Cyclic guanosine 3',5'-monophosphate (cyclic GMP) has been implicated in modulating the effects of anesthesia. We hypothesized that limiting the breakdown of cyclic GMP through selective phosphodiesterase inhibition would influence propofol sedation requirements and plasma cyclic GMP concentrations. Ten volunteers received 100 mg of sildenafil or placebo orally in this placebo-controlled, double-blind, randomized crossover pilot study: Propofol sedation was achieved using a target-controlled infusion system until loss of verbal contact (LVC). Plasma cyclic GMP concentrations were determined at baseline, LVC, and 30 min after LVC. There was no difference in the amount of propofol used, predicted plasma concentration, or duration of sedation in volunteers after sildenafil compared with placebo treatment. Return of spontaneous verbal contact was faster after sildenafil (4 [3-8] min versus 6 [3-5] min, median [range], P = 0.019). Cyclic GMP concentrations were reduced during propofol sedation in the placebo group compared with baseline (P < 0.004). The plasma cyclic GMP concentrations were larger (P = 0.004) at LVC in the sildenafil group compared with placebo. We have shown that selective phosphodiesterase 5 inhibition decreases recovery time from propofol sedation without affecting propofol requirements. The decrease of plasma cyclic GMP concentrations during propofol sedation in the placebo group indicates a potential role of cyclic GMP in propofol anesthesia in humans.

Original languageEnglish
Pages (from-to)1050-1053
Number of pages4
JournalAnesthesia and Analgesia
Volume101
DOIs
Publication statusPublished - 2005

Keywords

  • ALVEOLAR ANESTHETIC CONCENTRATION
  • OXIDE SYNTHASE ACTIVITY
  • NITRIC-OXIDE
  • HALOTHANE ANESTHESIA
  • NERVOUS-SYSTEM
  • CGMP
  • MONOPHOSPHATE
  • THRESHOLD
  • REGIONS
  • TARGET

Cite this

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title = "Selective phosphodiesterase 5 inhibition does not reduce propofol sedation requirements but affects speed of recovery and plasma cyclic guanosine 3 ',5 '-monophosphate concentrations in healthy volunteers",
abstract = "Cyclic guanosine 3',5'-monophosphate (cyclic GMP) has been implicated in modulating the effects of anesthesia. We hypothesized that limiting the breakdown of cyclic GMP through selective phosphodiesterase inhibition would influence propofol sedation requirements and plasma cyclic GMP concentrations. Ten volunteers received 100 mg of sildenafil or placebo orally in this placebo-controlled, double-blind, randomized crossover pilot study: Propofol sedation was achieved using a target-controlled infusion system until loss of verbal contact (LVC). Plasma cyclic GMP concentrations were determined at baseline, LVC, and 30 min after LVC. There was no difference in the amount of propofol used, predicted plasma concentration, or duration of sedation in volunteers after sildenafil compared with placebo treatment. Return of spontaneous verbal contact was faster after sildenafil (4 [3-8] min versus 6 [3-5] min, median [range], P = 0.019). Cyclic GMP concentrations were reduced during propofol sedation in the placebo group compared with baseline (P < 0.004). The plasma cyclic GMP concentrations were larger (P = 0.004) at LVC in the sildenafil group compared with placebo. We have shown that selective phosphodiesterase 5 inhibition decreases recovery time from propofol sedation without affecting propofol requirements. The decrease of plasma cyclic GMP concentrations during propofol sedation in the placebo group indicates a potential role of cyclic GMP in propofol anesthesia in humans.",
keywords = "ALVEOLAR ANESTHETIC CONCENTRATION, OXIDE SYNTHASE ACTIVITY, NITRIC-OXIDE, HALOTHANE ANESTHESIA, NERVOUS-SYSTEM, CGMP, MONOPHOSPHATE, THRESHOLD, REGIONS, TARGET",
author = "T Engelhardt and J MacDonald and Galley, {H F} and Webster, {N R}",
year = "2005",
doi = "10.1213/01.ane.0000168264.41341.7d",
language = "English",
volume = "101",
pages = "1050--1053",
journal = "Anesthesia and Analgesia",
issn = "0003-2999",
publisher = "Lippincott Williams and Wilkins",

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TY - JOUR

T1 - Selective phosphodiesterase 5 inhibition does not reduce propofol sedation requirements but affects speed of recovery and plasma cyclic guanosine 3 ',5 '-monophosphate concentrations in healthy volunteers

AU - Engelhardt, T

AU - MacDonald, J

AU - Galley, H F

AU - Webster, N R

PY - 2005

Y1 - 2005

N2 - Cyclic guanosine 3',5'-monophosphate (cyclic GMP) has been implicated in modulating the effects of anesthesia. We hypothesized that limiting the breakdown of cyclic GMP through selective phosphodiesterase inhibition would influence propofol sedation requirements and plasma cyclic GMP concentrations. Ten volunteers received 100 mg of sildenafil or placebo orally in this placebo-controlled, double-blind, randomized crossover pilot study: Propofol sedation was achieved using a target-controlled infusion system until loss of verbal contact (LVC). Plasma cyclic GMP concentrations were determined at baseline, LVC, and 30 min after LVC. There was no difference in the amount of propofol used, predicted plasma concentration, or duration of sedation in volunteers after sildenafil compared with placebo treatment. Return of spontaneous verbal contact was faster after sildenafil (4 [3-8] min versus 6 [3-5] min, median [range], P = 0.019). Cyclic GMP concentrations were reduced during propofol sedation in the placebo group compared with baseline (P < 0.004). The plasma cyclic GMP concentrations were larger (P = 0.004) at LVC in the sildenafil group compared with placebo. We have shown that selective phosphodiesterase 5 inhibition decreases recovery time from propofol sedation without affecting propofol requirements. The decrease of plasma cyclic GMP concentrations during propofol sedation in the placebo group indicates a potential role of cyclic GMP in propofol anesthesia in humans.

AB - Cyclic guanosine 3',5'-monophosphate (cyclic GMP) has been implicated in modulating the effects of anesthesia. We hypothesized that limiting the breakdown of cyclic GMP through selective phosphodiesterase inhibition would influence propofol sedation requirements and plasma cyclic GMP concentrations. Ten volunteers received 100 mg of sildenafil or placebo orally in this placebo-controlled, double-blind, randomized crossover pilot study: Propofol sedation was achieved using a target-controlled infusion system until loss of verbal contact (LVC). Plasma cyclic GMP concentrations were determined at baseline, LVC, and 30 min after LVC. There was no difference in the amount of propofol used, predicted plasma concentration, or duration of sedation in volunteers after sildenafil compared with placebo treatment. Return of spontaneous verbal contact was faster after sildenafil (4 [3-8] min versus 6 [3-5] min, median [range], P = 0.019). Cyclic GMP concentrations were reduced during propofol sedation in the placebo group compared with baseline (P < 0.004). The plasma cyclic GMP concentrations were larger (P = 0.004) at LVC in the sildenafil group compared with placebo. We have shown that selective phosphodiesterase 5 inhibition decreases recovery time from propofol sedation without affecting propofol requirements. The decrease of plasma cyclic GMP concentrations during propofol sedation in the placebo group indicates a potential role of cyclic GMP in propofol anesthesia in humans.

KW - ALVEOLAR ANESTHETIC CONCENTRATION

KW - OXIDE SYNTHASE ACTIVITY

KW - NITRIC-OXIDE

KW - HALOTHANE ANESTHESIA

KW - NERVOUS-SYSTEM

KW - CGMP

KW - MONOPHOSPHATE

KW - THRESHOLD

KW - REGIONS

KW - TARGET

U2 - 10.1213/01.ane.0000168264.41341.7d

DO - 10.1213/01.ane.0000168264.41341.7d

M3 - Article

VL - 101

SP - 1050

EP - 1053

JO - Anesthesia and Analgesia

JF - Anesthesia and Analgesia

SN - 0003-2999

ER -