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At least 865 records · Page 48Linked to original sources
PubMed2000

Multiple dose pharmacokinetics of oral transmucosal fentanyl citrate in healthy volunteers.

BACKGROUND: Oral transmucosal fentanyl citrate (OTFC) is a solid form of fentanyl that delivers the drug through the oral mucosa. The clinical utility of multiple doses of OTFC in the treatment of "breakthrough" cancer pain is under evaluation. The aim of this study was to test the hypothesis that the pharmacokinetics of OTFC do not change with multiple dosing. METHODS: Twelve healthy adult volunteers received intravenous fentanyl (15 microg/kg) or OTFC (three consecutive doses of 800 microg) on separate study sessions. Arterial blood samples were collected for determination of fentanyl plasma concentration by radioimmunoassay. The descriptive pharmacokinetic parameters (maximum concentration, minimum concentration, and time to maximum concentration) were identified from the raw data and subjected to a nonparametric analysis of variance. Population pharmacokinetic models for all subjects and separate models for each subject were developed to estimate the pharmacokinetic parameters of fentanyl after multiple OTFC doses. RESULTS: The shapes of the profiles of plasma concentration versus time for each dose of OTFC were grossly similar. No change was noted for maximum concentration or time to maximum concentration over the three doses, while minimum concentration did show a significantly increasing trend. Terminal half-lives for intravenous fentanyl and OTFC were similar. A two-compartment population pharmacokinetic model adequately represented the central tendency of the data from all subjects. Individual subject data were best described by either two- or three-compartment pharmacokinetic models. These models demonstrated rapid and substantial absorption of OTFC that did not change systematically with time and multiple dosing. CONCLUSIONS: The pharmacokinetics of OTFC were similar among subjects and did not change with multiple dosing. Multiple OTFC dosing regimens within the dosage schedule examined in this study can thus be formulated without concern about nonlinear accumulation.

Administration, Oral↗
PubMed2000

Pharmacokinetics of human cerebral opioid extraction: a comparative study on sufentanil, fentanyl, and alfentanil in a patient after severe head injury.

BACKGROUND: The pharmacodynamic differences in time to onset and dissipation of effect of sufentanil, fentanyl, and alfentanil probably result from different rates of blood-brain equilibration. The authors investigated this hypothesis in humans. METHODS: After simultaneous central venous bolus application of sufentanil (10 microg), fentanyl (100 microg), and alfentanil (1,000 microg), arterial and jugular bulb blood samples were drawn simultaneously at 20, 30, 45, 60, 75, 90, 105, 120, 140, 160, 180, 210, 240, 300, 360, and 420 s from 19 patients during the postacute stage of head injury with normal intracranial pressure, cerebral perfusion pressure, and cerebral oxygen metabolism during normocapnia. RESULTS: Peak brain concentration, indicated by equilibrium between arterial and jugular bulb opioid concentrations, was achieved for alfentanil at 45 s, for sufentanil at 5 min, and for fentanyl at 6 min. The corresponding median time intervals (fifth and ninety-fifth percentiles) to reach 50% of peak brain concentration were 15 (14-18), 25 (18-38) and 35 (25-45) s, respectively. Uptake was highest 20 s after bolus and decreased continuously for fentanyl and sufentanil, whereas alfentanil uptake was biphasic. The ratio of the relative amounts of sufentanil, fentanyl, and alfentanil retained in the brain at peak brain concentration was 1x:x6x:x90. CONCLUSIONS: The differences in the time lag between changes in serum concentrations and drug effect after bolus application of nearly equipotent doses of sufentanil, fentanyl, and alfentanil originate from the different times required to reach blood-brain equilibration, mainly depending on different levels and different time profiles of arterial blood concentrations caused by the different tissue distribution volumes.

Adolescent↗
PubMed2003

Fentanyl decreases Ca2+ currents in a population of capsaicin-responsive sensory neurons.

BACKGROUND: Neuraxial opioids produce analgesia in part by decreasing excitatory neurotransmitter release from primary nociceptive neurons, an effect that may be due to inhibition of presynaptic voltage-activated Ca2+ channels. The purpose of this study was to determine whether opioids decrease Ca2+ currents (I Ca ) in primary nociceptive neurons, identified by their response to the algogenic agent capsaicin. METHODS: I was recorded from acutely isolated rat dorsal root ganglion neurons using the whole cell patch clamp technique before, during, and after application of the micro -opioid agonist fentanyl (0.01-1 micro m). Capsaicin was applied to each cell at the end of the experiment. RESULTS: Fentanyl reduced I Ca in a greater proportion of capsaicin-responsive cells (62 of 106, 58%) than capsaicin-unresponsive cells (2 of 15, 13%; P < 0.05). Among capsaicin-responsive cells, the decrease in I Ca was 38 +/- 3% (n = 36, 1 micro m) in fentanyl-sensitive cells just 7 +/- 1% (n = 15, 1 micro m; P < 0.05) in fentanyl-insensitive cells. Among capsaicin-responsive cells, I Ca inactivated more rapidly in fentanyl-sensitive cells (tau, 52 +/- 4 ms, n = 22) than in fentanyl-insensitive cells (93 +/- 14 ms, n = 24; P < 0.05). This was not due to differences in the types of Ca2+ channels expressed as the magnitudes of omega-conotoxin GVIA-sensitive (N-type), nifedipine-sensitive (L-type), and GVIA/nifedipine-resistant (primarily P-/Q-type) components of I Ca were similar. CONCLUSIONS: The results show that opioid-sensitive Ca2+ channels are expressed by very few capsaicin-unresponsive neurons but by more than half of capsaicin-responsive neurons. The identity of the remaining capsaicin-responsive (and therefore presumed nociceptive) neurons that express opioid-insensitive Ca2+ channels is unknown but may represent a potential target of future non-opioid-based therapies for acute pain.

Agatoxins↗
PubMed2004

Effects of isoflurane versus fentanyl-nitrous oxide anesthesia on long-term outcome from severe forebrain ischemia in the rat.

BACKGROUND: This study examined long-term outcome from severe forebrain ischemia in the rat, as a function of anesthetic given during the ischemic injury. METHODS: Rats were subjected to 10 min of near-complete forebrain ischemia while anesthetized with either 1.4% isoflurane or 70% nitrous oxide-fentanyl. Neurologic and histologic outcomes were measured at 5 days, 3 weeks, or 3 months after ischemia. RESULTS: At 5 days, isoflurane-anesthetized rats had less damage than did fentanyl-nitrous oxide-anesthetized rats (mean +/- SD, percent alive hippocampal CA1 neurons = 58+/-29 vs. 20+/-16, respectively; P = 0.011). This was accompanied by improved motor function in the isoflurane group (P = 0.002). At 3 weeks, there was no difference between groups for either outcome variable (percent alive CA1 neurons = 35+/-26 and 36+/-28 for isoflurane and fentanyl-nitrous oxide, respectively). Similarly, at 3 months, there was no difference between groups (percent alive CA1 neurons = 56+/-27 and 60+/-27 for isoflurane and fentanyl-nitrous oxide, respectively). Morris water maze performance at 3 months was similar between anesthetic groups and was also similar to sham performance. The percent alive CA1 neurons in the fentanyl-nitrous oxide group increased with duration of recovery (P = 0.004). There were no differences among isoflurane groups over time (5 days vs. 3 weeks, P = 0.26; 5 days vs. 3 months, P = 0.99; 3 week vs. 3 months, P = 0.32). CONCLUSIONS: This study found no change in the percent alive CA1 hippocampal neurons as a function of duration of recovery from severe forebrain ischemia in isoflurane anesthetized rats. In contrast, the percent alive CA1 neurons in fentanyl-nitrous oxide-anesthetized rats tripled over 3 months of recovery. The natural history of long-term responses to forebrain ischemia requires further study before conclusions can be drawn with respect to the permanence of isoflurane neuroprotection.

Anesthesia↗
PubMed2004

Influence of age on the pharmacokinetics and pharmacodynamics of oral transmucosal fentanyl citrate.

BACKGROUND: Cancer pain is primarily a problem of older persons. Oral transmucosal fentanyl citrate (OTF) was developed to provide rapid analgesia and is the first drug specifically approved for treating breakthrough cancer pain. Fentanyl in OTF is absorbed across the oral mucosa but a considerable portion is swallowed and absorbed enterally. The effects of age on OTF pharmacokinetics and pharmacodynamics are unknown. This investigation evaluated OTF disposition and clinical effects in older (60-75 yr) compared with younger (18-40 yr) volunteers. METHODS: Healthy young (26 +/- 6 yr) and older (67 +/- 6 yr) volunteers (n = 12 each) were studied in an Institutional Review Board approved protocol. They received OTF (10 microg/kg). Plasma fentanyl and norfentanyl concentrations were determined by mass spectrometry. Fentanyl effects were measured by dark-adapted pupil diameter and by subjective self-assessments using visual analog scales. RESULTS: Plasma fentanyl and norfentanyl concentrations and pharmacokinetic parameters did not differ between younger and older subjects. Maximum pupil diameter change from baseline was significantly less in older (3.1 +/- 0.7 mm) compared with younger (4.5 +/- 1.1 mm) subjects (P < 0.05). OTF-dependent subjective assessments of alertness/sedation, energy level, confusion, clumsiness, anxiety, and nausea did not differ in the older subjects. DISCUSSION: The pharmacokinetics of OTF were not altered in older volunteers. In contrast, there was a somewhat diminished response to the miotic effects of fentanyl in older subjects. No change in OTF dosing in the elderly would appear necessary because of altered pharmacokinetics. If the response to OTF in older patients is similar to that in older volunteers and miosis is representative of analgesia and respiratory depression, then changes in OTF dosing with age alone do not appear indicated.

Administration, Oral↗
PubMed2004

Myocardial performance index with sevoflurane-pancuronium versus fentanyl-midazolam-pancuronium in infants with a functional single ventricle.

BACKGROUND: Patients with congenital heart disease characterized by a functional single ventricle make up an increasing number of patients presenting for cardiac or noncardiac surgery. Conventional echocardiographic methods to measure left ventricular function, i.e., ejection fraction, are invalid in these patients because of altered ventricular geometry. Two recently described Doppler echocardiographic modalities, the myocardial performance index and Doppler tissue imaging, can be applied to single-ventricle patients because they are independent of ventricular geometry. This study assessed the changes in myocardial performance index and Doppler tissue imaging in response to two anesthetic regimens, fentanyl-midazolam-pancuronium and sevoflurane-pancuronium. METHODS: Thirty patients aged 4-12 months with a functional single ventricle were randomized to receive fentanyl-midazolam or sevoflurane. Myocardial performance index and Doppler tissue imaging were measured by transthoracic echocardiography at baseline and two clinically relevant dose levels. RESULTS: Sixteen patients receiving sevoflurane and 14 receiving fentanyl-midazolam were studied. Myocardial performance index was unchanged from baseline with either agent (fentanyl-midazolam: 0.50 +/- 15 baseline vs. 0.51 +/- 0.15 at dose 2; sevoflurane: 0.42 +/- 0.14 baseline vs. 0.46 +/- 0.09 at dose 2). Doppler tissue imaging S (systolic)- and E (early diastolic)-wave velocities in the lateral ventricular walls at the level of the atrioventricular valve annulus were unchanged in the sevoflurane group; however, both Doppler tissue imaging S- and E-wave velocities were decreased significantly from baseline at dose 1 and dose 2 with fentanyl-midazolam, consistent with decreased longitudinal systolic and diastolic ventricular function. CONCLUSIONS: Myocardial performance index, a global measurement of combined systolic and diastolic ventricular function, is not affected by commonly used doses of fentanyl-midazolam or sevoflurane in infants with a functional single ventricle.

Anesthetics, Inhalation↗
PubMed2005

Chronobiology of subarachnoid fentanyl for labor analgesia.

BACKGROUND: Chronobiology studies the recurrent biologic rhythms that directly affect how an organism interacts with its environment and how its environment affects the organism. The purpose of this study is to determine whether the time of administration influences the analgesic duration of the commonly used subarachnoid fentanyl for labor analgesia. METHODS: After institutional review board approval and informed consent were obtained, 77 healthy nulliparous women in active labor requesting neuraxial analgesia were assigned to one of two groups, based on the time of combined spinal-epidural analgesia placement: the day group, for the time period from 12:00 to 18:00, and the night group, for the period from 20:00 to 02:00. Combined spinal-epidural analgesia was performed with 20 microg subarachnoid fentanyl. An epidural catheter was inserted but not dosed until patients requested further analgesia. Dynamic data were recorded at 5-min intervals for 20 min initially and then every 15 min. The analgesic duration was defined as the time from subarachnoid fentanyl injection to the time the patient requested further analgesia. RESULTS: Seventy evaluable patients completed the study, with 35 per group. Patient demographics, visual analog pain scale scores, and labor characteristics were similar between groups, but the duration (mean +/- SD) for subarachnoid fentanyl labor analgesia was 92 +/- 34 min for the day group and 67 +/- 21 min for the night group (P < 0.001). CONCLUSIONS: The results indicate that chronobiology of subarachnoid fentanyl plays a significant role of up to 27% difference in labor analgesic duration between the two administration time periods studied. Chronobiology should be incorporated in future comparative studies or analysis of previous studies on subarachnoid fentanyl.

Adult↗
PubMed2006

A comparison of the effect of high- and low-dose fentanyl on the incidence of postoperative cognitive dysfunction after coronary artery bypass surgery in the elderly.

BACKGROUND: Postoperative cognitive dysfunction (POCD) after coronary artery bypass graft surgery is a common complication for which, despite many clinical investigations, no definitive etiology has been found. The current use of both high- and low-dose fentanyl as anesthetic techniques allowed us to investigate the effect of fentanyl on the incidence of POCD. METHODS: Three hundred fifty patients scheduled to undergo elective coronary artery bypass graft surgery were randomized to receive either high-dose fentanyl (50 microg/kg) or low-dose fentanyl (10 mug/kg) as the basis of the anesthetic. All patients underwent neuropsychological testing before surgery and at 1 week, 3 months, and 12 months after surgery. RESULTS: One hundred sixty-eight patients in the low-dose group and 158 patients in the high-dose group were included in the final analysis. Neuropsychological testing was performed on 88%, 93%, and 92% of patients at 1 week, 3 months, and 12 months, respectively. There was no difference between group mean scores at any of the three testing times. Analysis of individual patients by the 20% rule did not detect any differences between groups. The one SD rule, which has fewer false-positive results, detected significantly more patients with POCD in the low-dose group than in the high-dose group at 1 week (23.6% vs. 13.7%; P = 0.03) but not at the other testing times. Patients with POCD spent an average of 1.2 days longer in the hospital than those without POCD (P = 0.021). CONCLUSIONS: High-dose fentanyl is not associated with a difference in the incidence of POCD at 3 or 12 months after surgery. Low-dose fentanyl leads to shorter postoperative ventilation times and may be associated with a greater incidence of POCD 1 week after surgery. Early POCD is associated with an increased duration of stay in the hospital.

Aged↗
PubMed1995

Transdermal fentanyl in combination with initial intravenous dose titration by patient-controlled analgesia.

Two studies including a total of 70 patients evaluated the efficacy and side effects of a combination of initial patient-controlled analgesia (PCA) for dose finding with transdermal fentanyl administration. Patients, requiring strong opioids for severe cancer pain, received intravenous (i.v.) fentanyl on an on-demand basis over a 24 h period. The amount of fentanyl administered was then used for selecting a suitable transdermal therapeutic system (TTS), which remained in place for 72 h. The size of the second TTS was adjusted according to the amount of supplementary i.v. fentanyl required on day 3. Beginning on day 4, oral or subcutaneous morphine was made available as a rescue medication. The use of TTS fentanyl in combination with initial dose titration using PCA resulted in rapid and statistically significant pain relief in both studies. A respiratory rate below 8 per minute was observed in three patients. Due to adequate symptomatic treatment, other moderate and severe symptoms were relatively rare. TTS fentanyl was shown to be an effective, safe and simple method for long-term pain relief in cancer patients and presents an interesting novel option in the treatment of cancer pain.

Administration, Cutaneous↗
PubMed1995

Ketorolac versus fentanyl for postoperative pain management in outpatients.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of i.v. ketorolac and fentanyl for moderate to severe postoperative pain in patients undergoing elective surgery in an ambulatory surgery unit. DESIGN: A double-blind randomized trial. SETTING: An ambulatory surgery unit in a university-affiliated hospital. PATIENTS: Sixty-nine patients undergoing elective laparoscopy, inguinal hernia repair, or knee arthroscopy were enrolled. INTERVENTION: Patients were randomly assigned to receive intravenous ketorolac 30 mg (n = 38) or fentanyl 50 micrograms (n = 31) for moderate to severe postoperative pain. OUTCOME MEASURES: Pain, assessed using a 100-mm visual analog scale and a 5-point verbal pain scale; adverse effects, as well as vital signs were recorded every 15 min for 150 min or until discharge from the postanesthesia care unit, 6 and 24 h after discharge. RESULTS: Pain reduction on both visual analog and verbal scales was significantly greater with fentanyl than ketorolac at 15 min. In addition, the proportion of patients requiring remedication at the 15-min time point was significantly greater in the ketorolac group. However, there were no significant differences between fentanyl and ketorolac between 30 and 150 min after surgery. Notably, pain reduction was significantly greater with ketorolac on the verbal scale at the 6 h measurement. CONCLUSIONS: Ketorolac appears not be as effective as fentanyl in treating early postoperative pain. Although fentanyl still appears to be the drug of choice in the early postoperative period, the parenteral use of ketorolac was more effective during the later postoperative period in providing longer lasting analgesia.

Adult↗
PubMed1993

Pharmacokinetics of continuous infusions of fentanyl in critically ill children.

OBJECTIVE: To determine the pharmacokinetics of fentanyl when used as a long-term continuous infusion for sedation/analgesia in mechanically ventilated critically ill infants and children. DESIGN: Prospective, case series. SETTING: A university hospital pediatric intensive care unit (ICU). PATIENTS: Nineteen mechanically ventilated infants and children (0.05 to 14 yrs of age) who received continuous infusions of fentanyl for > 24 hrs. INTERVENTIONS: None. MEASUREMENTS: Plasma concentrations of fentanyl were measured 1 hr after a loading dose and at various intervals during and after the infusions were discontinued. Noncompartmental pharmacokinetic variables, total body clearance, volume of distribution at steady state, and terminal elimination half-life were calculated. Clinical sedation scores, ventilatory settings, pupillary size and reactivity, and patient demographics were recorded. RESULTS: After the use of fentanyl by long-term infusion, the volume of distribution at steady state was increased 15.2 L/kg (range 5.1 to 30.5) and the terminal elimination half-life was prolonged 21.1 hrs (range 11.2 to 36.0) compared with previous studies. Clearance was rapid and consistent with other studies. There was a large interpatient variability in clearance that was age dependent. Clearance did not appear to increase over time. CONCLUSIONS: Total body clearance of fentanyl is highly variable and it should be dosed to effect. Patients seen in a pediatric ICU may require a ten-fold variability in fentanyl infusion rates to achieve similar levels of sedation.

Adolescent↗
PubMed1999

Subcutaneous administration of fentanyl and midazolam to prevent withdrawal after prolonged sedation in children.

OBJECTIVE: To determine the efficacy of switching to subcutaneous fentanyl with or without midazolam to prevent withdrawal after prolonged sedation in children in the pediatric intensive care unit (PICU). DESIGN: Retrospective review of hospital records. SETTING: Tertiary care center, PICU. PATIENTS: The cohort for the study included patients who had received subcutaneous fentanyl with or without midazolam to prevent withdrawal after prolonged sedation in the PICU. MEASUREMENTS AND MAIN RESULTS: Subcutaneous fentanyl with or without midazolam was administered to nine patients ranging in age from 3 to 7 yrs (mean, 4.4 +/- 1.8 yrs) and ranging in weight from 11 to 31 kg (mean, 20.1 +/- 6.8 kg). All patients required prolonged administration of fentanyl with or without midazolam during mechanical ventilation for respiratory failure. The starting infusion rate for subcutaneous fentanyl varied from 5 to 9 microg/kg/hr (mean, 7.1 +/- 1.4 microg/kg/hr). Four patients also received subcutaneous midazolam at a rate of 0.15 to 0.3 mg/kg/hr (mean, 0.24 mg/kg/hr). Subcutaneous access was maintained for 3-7 days (mean, 5.7 +/- 1.4 days) in the nine patients. No problems with the subcutaneous access were noted during treatment. The fentanyl infusion was decreased by 1 microg/kg/hr every 12-24 hrs and the midazolam infusion was decreased by 0.05 mg/kg/hr every 12-24 hrs. No patient demonstrated signs of symptoms of moderate to severe withdrawal. CONCLUSION: The subcutaneous route provides an effective alternative to intravenous administration. It allows for gradual weaning from sedative/analgesic agents after prolonged sedation while eliminating the need to maintain intravenous access.

Analgesics, Opioid↗
PubMed2000

Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants.

OBJECTIVE: To assess the occurrence of muscle rigidity after fentanyl administration in premature and term neonates. DESIGN: Prospective case series, observational study. SETTING: A university hospital neonatal intensive care unit. PATIENTS: 8/89 preterm and term infants (25-40 wks gestational age) who received fentanyl for perioperative analgesia and sedation or intensive care procedures. INTERVENTIONS: Mechanical or bag mask ventilation and antagonization with naloxone. MEASUREMENTS AND MAIN RESULTS: We observed chest wall rigidity in 8 patients after low dosage of fentanyl (3-5 microg/kg body weight). All patients presented with respiratory distress, hypercapnia, and hypoxemia leading to bradycardia. In two patients, laryngospasm was noted and associated with muscle rigidity, thus making intubation impossible. Naloxone (20-40 microg/kg body weight) reversed the laryngospasm and muscle rigidity immediately, allowing restitution within 1 min. In our patient population, we found fentanyl-induced chest wall rigidity in 4% of neonates after fentanyl administration. CONCLUSION: Even low doses of fentanyl can lead to thoracic rigidity in neonates. Additionally, we observed laryngospasm in two patients and speculate that it might be a variant of muscle rigidity.

Fentanyl↗
PubMedDate not supplied

Multiple sites for the cardiovascular actions of fentanyl in rats.

We studied the cardiovascular effects of intravenously administered fentanyl in normotensive rats anesthetized with pentobarbital and artificially ventilated. Fentanyl induced an immediate and short-lasting fall in blood pressure and heart rate by an action on opiate receptors localized at vagal nerve endings. Bilateral vagotomy suppressed these effects. The bradycardia, suppressed by bilateral vagotomy and reduced by previous administration of atropine, seemed to be due to a vagovagal reflex. Inhibition of the sympathetic outflow may also occur, because in pithed rats fentanyl failed to lower blood pressure. This masks a direct central stimulation of sympathetic outflow, because in bilaterally vagotomized rats fentanyl induced an alpha-adrenoceptor-blocking drug-sensitive hypertension which was insensitive to adrenalectomy. In addition, stimulation of cardiac opiate receptors by high doses of fentanyl lead to bradycardia in pithed rats. We conclude that in the rat, fentanyl administered intravenously can act at three different levels on cardiovascular regulation: the vagal nerve endings, the brain, and the heart.

Adrenalectomy↗
PubMed2006

A prospective randomized double-blind trial of the use of intrathecal fentanyl in patients undergoing lumbar spinal surgery.

STUDY DESIGN: A randomized, double-blind controlled study. OBJECTIVE: To assess the efficacy and safety of intrathecal fentanyl in the relief of postoperative pain in patients undergoing lumbar spinal surgery. SUMMARY OF BACKGROUND DATA: Fentanyl has been used as a spinal analgesic in surgery and obstetrics with several studies promoting its efficacy and safety. There is no evidence in the literature about intrathecal fentanyl in lumbar spinal surgery. Previous studies have looked at the use of intrathecal morphine and conclude that it is effective but also associated with respiratory depression. METHODS: Sixty patients undergoing posterior lumbar spine decompression with or without instrumented fusion were randomized to receive either 15 mug of fentanyl intrathecally under direct vision or nothing just before wound closure. After surgery, all patients received intravenous (IV) morphine via patient-controlled analgesia system (PCA) syringe driver. Outcome measures included visual analogue scores (VAS) for pain, time to first bolus of IV morphine PCA, and total amount of morphine PCA used. RESULTS: The patients who received fentanyl demonstrated a significant decrease in their mean pain VAS, an increase in the time to first PCA bolus, and a 41% reduction in the total PCA morphine received. No patients had respiratory compromise requiring treatment. There was no significant difference between the two groups with respect to age, gender, and case mix. CONCLUSION: Intrathecal fentanyl is effective at reducing pain and morphine PCA use after lumbar spinal surgery with minimal respiratory depression.

Adult↗
PubMed2004

Opioid-induced respiratory depression: a mathematical model for fentanyl.

In this paper, respiratory depressant effects of fentanyl are described quantitatively by a mathematical model. The model is an extension of a previous one, which reproduces the human ventilatory control system on a physiological basis. It includes the following: three compartments for gas storage and exchange (lungs, body tissue, and brain tissue); the main mechanisms involved in ventilation control (peripheral chemoreceptors, central chemoreceptors, and the central hypoxic depression); and local blood flow regulation. The effects of fentanyl on the respiratory system include a decrease in peripheral and central chemoreceptor gains on ventilation and a direct inhibition of respiratory neural activity. All parameters in the model were chosen according to the literature. The model is able to reproduce the ventilatory effects of fentanyl in several conditions: 1) constant levels of fentanyl; 2) after a bolus injection; 3) at fixed levels of P(ETCO2); and 4) after artificial ventilation. According to the model, in spontaneously breathing subjects, minute ventilation depends on two opposing actions: fentanyl inhibitory influences, which depress ventilation, reducing oxygen tension and increasing CO2 tension, and the consequent activation of chemoreceptors, which stimulates ventilation. Simulations of anesthetized patients resuming spontaneous breathing after artificial ventilation demonstrate the risk of prolonged apnea and tissue hypoxemia. A safe transition can be achieved by increasing patient PCO2 toward the end of artificial ventilation, because an advanced chemoreceptor stimulation is produced, which promptly counteracts fentanyl-induced inhibition at cessation of artificial ventilation.

Adaptation, Physiological↗
PubMed1987

Comparison of epidural fentanyl with sufentanil. Analgesia and side effects after a single bolus dose during elective caesarean section.

Duration of analgesia and side effects following single bolus doses of epidural fentanyl (100 micrograms) or sufentanil (10, 20, 30 or 50 micrograms) were studied in 50 patients who underwent Caesarean section under epidural anaesthesia. Fewer patients experienced pain peroperatively in the fentanyl group than in a joint group of those given sufentanil 20 or 30 micrograms (p less than 0.05). The combined fentanyl and sufentanil 50 micrograms groups had fewer patients in pain than the sufentanil 10 micrograms group at 3 hours after injection (p less than 0.05). Patients given fentanyl also had a longer pain-free interval than those who received sufentanil 10 micrograms (p less than 0.02). The sufentanil 50 micrograms group had more patients asleep than the 10 micrograms group and also had more patients with pruritus than the 10 micrograms or 30 micrograms groups (p less than 0.02). The patients given sufentanil 30 and 50 micrograms had more emetic sequelae than those who received sufentanil 10 and 20 micrograms or fentanyl 100 micrograms (p less than 0.05). There was no detectable excretion of drug into breast milk and no significant respiratory depression at the time of first postoperative analgesia in the patients who received fentanyl or 30 micrograms or less of sufentanil.

Analgesics↗
PubMed1990

Inhaled fentanyl as a method of analgesia.

A study was undertaken to investigate the use of fentanyl by aerosol for postoperative analgesia. Seven patients had placebo, six received fentanyl 100 micrograms and seven were given fentanyl 300 micrograms. A significant improvement in postoperative pain, as assessed by linear visual analogue scale, was achieved in the higher dose group, and in both fentanyl groups the time to alternative analgesia was significantly longer than in the control group. Serum fentanyl levels after inhalation of 100 micrograms reached a plateau around 0.04 ng/ml and after 300 micrograms at around 0.1 ng/ml after 15 minutes. Inhaled fentanyl may have a useful analgesic effect despite these low serum levels; this supports the hypothesis that the mode of analgesia from inhaled opioids may be different from that after other routes of administration. There were no adverse effects such as respiratory depression, bronchospasm, nausea or drowsiness.

Adolescent↗