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PubMed2003

Wound infiltration with ropivacaine and fentanyl: effects on postoperative pain and PONV after breast surgery.

STUDY OBJECTIVE: To determine whether postoperative wound infiltration with local anesthetics combined with fentanyl improves analgesia following breast surgery; and to investigate awakening and postoperative nausea/vomiting. DESIGN: Prospectively randomized clinical study. SETTING: University hospital. PATIENTS: 45 ASA physical status I and II patients scheduled for breast surgery. INTERVENTIONS: Patients were prospectively randomized and assigned to one of three treatments during general anesthesia: postsurgical wound infiltration with ropivacaine 0.375%; wound infiltration with ropivacaine 0.375% combined with fentanyl 0.5 microg/kg; and intravenous (i.v.) fentanyl 0.5 microg/kg before skin incision and no wound infiltration. Time to first verbal response, pain at rest, postoperative nausea and vomiting, and ketobemidone and dixyrazine utilization were compared. MEASUREMENTS AND MAIN RESULTS: Time to first verbal response was significantly shorter in the i.v. fentanyl group compared to both infiltration groups (8.1 +/- 4.5 min vs. 15.3 +/- 4.3, and 12.0 +/- 5.0 min; p < 0.05, respectively). Postoperative pain at rest, and nausea and vomiting occurred with similar frequencies in the groups. Ketobemidone utilization in both infiltration groups, (2.4 +/- 1.8 mg and 3.1 +/- 1.8 mg, respectively) was not different compared to the i.v. fentanyl group (2.9 +/- 2.0 mg; NS). There were no differences in postoperative antiemetic requirements during the first, second and third two-hour periods postoperatively. The dixyrazine consumption was similar in the three groups, (0.9 +/- 1.5 mg, 0.8 +/- 1.3 mg, and 1.4 +/- 1.8 mg, respectively; NS). CONCLUSION: Postsurgical ropivacaine wound infiltration, with or without adding fentanyl, demonstrates no differences in postoperative pain relief and nausea/vomiting compared to a balanced general anesthetic including i.v. fentanyl.

Amides↗
PubMed2000

Additional droperidol, not butorphanol, augments epidural fentanyl analgesia following anorectal surgery.

STUDY OBJECTIVE: To examine the effects of additional droperidol or butorphanol to epidural fentanyl infusion on postsurgical analgesia. DESIGN: Prospective, randomized, single blinded clinical study. SETTING: University-affiliated medical center. PATIENTS: 60 ASA physical status I and II patients undergoing anorectal surgery by one surgeon. INTERVENTIONS: Patients were randomly allocated to the following groups according to the medication that was continuously administered into the epidural space: 1) Group C (n = 20) received 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine; 2) Group D (n = 20) received 2.5 mg droperidol and 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine; and 3) Group B (n = 20) received 2 mg butorphanol and 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine over 24 hours postoperatively. MEASUREMENTS AND MAIN RESULT: Postsurgical analgesia and the incidence of fentanyl-related complications, such as nausea/vomiting, somnolence, pruritus, and respiratory depression, were assessed for 24 hours postoperatively. At 16 and 24 hours after surgery, 75% of patients in Group D reported no pain versus 35% in Group C (p < 0.05). In addition, the overall visual analogue scale examined at 24 hours was significantly lower in Group D than that in Group C (22 +/- 17 mm vs. 44 +/- 22 mm, respectively; p < 0.05). Simultaneously, the incidence of postoperative nausea/vomiting was lower in Group D compared with Group C (20% vs. 60%; p < 0.05). On the other hand, butorphanol did not modify the analgesic effects or complications of epidural fentanyl infusion. CONCLUSION: In this study population, additional droperidol, not butorphanol, improved postsurgical analgesia accompanied by less incidence of nausea/vomiting during epidural fentanyl administration.

Adjuvants, Anesthesia↗
PubMedDate not supplied

Supraspinal pupillary effects of intravenous and epidural fentanyl during isoflurane anesthesia.

BACKGROUND AND OBJECTIVES: Epidural fentanyl has been shown to gain rapid access to the circulation resulting in supraspinal effects. We compared the supraspinal effects of fentanyl via epidural versus intravenous (IV) routes, during isoflurane anesthesia. Supraspinal fentanyl effect was evaluated as a reduction of pupillary reflex dilation (PRD) measured with infrared pupillometry. METHODS: Eighteen patients undergoing abdominal procedures were studied during combined epidural and general anesthesia. General anesthesia was provided by 0.55 to 0.70% end-tidal isofurane in air:oxygen (50:50). Sensory block of the surgical field was established with bupivacaine 0.375% and confirmed by absence of PRD to cutaneous stimulation. A high cervical dermatome was then stimulated (60 to 70 mA) at 5-minute intervals via cutaneous needle electrodes, and PRD was measured with each stimulation, using infrared pupillometry. Baseline PRD was determined and then a randomized injection of cpidueral saline (n = 6), epidural fentanyl 3 microg/kg (n = 6), or IV fentanyl 3 microg/kg (n = 6) was given. Subsequently, PRD was measured at 5, 10, 20, 30, 40, 60, and 80 minutes. Maximum change in PRD and time to maximum change were calculated for each group. RESULTS: Following epidural injection, suppression of PRD was highly variable among subjects. The maximum suppression was 70+/-15% at 23.3+/-10.3 minutes for the epidural group and 96+/-3% at 10.8+/-7.4 min for the IV group (P<.0001). Epidural saline produced no effect. CONCLUSIONS: Supraspinal effects of epidural fentanyl can be assessed during general anesthesia using infrared pupillometry. Epidural fentanyl 3 microg/kg produces significant but variable supraspinal effects during 0.5 minimum alveolar concentration isoflurane anesthesia.

Adult↗
PubMed2006

The effect of fentanyl and remifentanil, with or without ketoprofen, on pain after thyroid surgery: a randomized-controlled trial.

BACKGROUND AND OBJECTIVES: This study was designed to quantify the additional postoperative analgesic efficacy of a single dose of ketoprofen in patients undergoing thyroid surgery using two different intraoperative analgesic regimens. METHODS: One hundred and twenty patients were randomly assigned to one of four groups: intraoperative fentanyl or remifentanil with or without ketoprofen (n = 30 for each group). Intravenous ketoprofen (1.5 mg kg-1) or saline was administered 45 min before the end of surgery. Pain scores, opioid demand and length of stay in the postanaesthesia care unit were assessed in a blinded manner. RESULTS: Patients receiving intraoperative fentanyl with saline had significantly lower visual analogue scale pain scores in the postanaesthesia care unit compared with those receiving intraoperative remifentanil with saline (55 +/- 10 mm vs. 80 +/- 18 mm, P < 0.05) and they stayed shorter in the postanaesthesia care unit (86 +/- 24 min vs. 126 +/- 37 min). In conjunction with intraoperative fentanyl, ketoprofen significantly decreased postoperative pain scores (40 +/- 10 mm, P < 0.05 compared with fentanyl alone) and opioid demand (4 of 30 patients vs. 14 of 30 patients compared with fentanyl alone, P < 0.05). Patients receiving intraoperative remifentanil had no additional analgesic benefit with ketoprofen. CONCLUSION: After thyroid surgery, patients receiving intraoperative fentanyl had lower pain scores and needed less rescue analgesia compared with patients receiving intraoperative remifentanil. The adjunction of ketoprofen further improved analgesia in patients who received intraoperative fentanyl only.

Adult↗
PubMed2000

Effects on the bispectral index during medium-high dose fentanyl induction with or without propofol supplement.

BACKGROUND: The search for a drug-independent monitor to determine depth of anaesthesia and hypnosis continues. The bispectral analysis (BIS) of the EEG correlates well with the clinical dose-response of hypnotic drugs during induction, but the effect on BIS of an opiate induction, as for coronary bypass surgery, is not known. METHODS: Fourteen patients scheduled for elective coronary bypass surgery were studied. BIS was recorded during induction in 7 patients receiving 10 microg/kg fentanyl without any hypnotic agent and in 7 patients receiving 0.5 mg/kg propofol before the fentanyl dose. RESULTS: The effect of fentanyl was very variable both regarding BIS and clinical response. Five of the 7 patients that received only fentanyl lost their response to verbal command within 8 min. BIS values at loss of response varied between 45 and 94. One patient remained awake with BIS 43. All 7 patients receiving propofol before the fentanyl dose lost their response to verbal command within 5 min. BIS values at the time for loss of response varied between 78 and 98. CONCLUSION: Loss of response to verbal command when a medium-high dose of fentanyl is used for induction cannot be distinguished from wakefulness with adequate sensitivity by BIS. The current BIS algorithm seems not to accurately reflect the hypnotic effects of fentanyl.

Aged↗
PubMed2002

Subeffective doses of dexketoprofen trometamol enhance the potency and duration of fentanyl antinociception.

The combination of classic non-steroidal antiinflammatory drugs (NSAIDs) with opiates induces more analgesia than the summed effect of each drug given separately. No studies have been performed using new generation NSAIDs and fentanyl nor on the duration of this effect. We have studied the analgesic effect of fentanyl alone and after the administration of subeffective doses of dexketoprofen trometamol in rat nociceptive responses. The responses were evoked by noxious mechanical stimulation and were recorded as single motor units in male Wistar rats anaesthetized with alpha-chloralose. The effective dose 50 (ED(50)) observed with fentanyl was 22.4 +/- 1.5 microg kg(-1) and full recovery was apparent 20 min later. The administration of a total dose of 40 microg kg(-1) of dexketoprofen trometamol did not induce any significant effect on the nociceptive responses. In the presence of dexketoprofen trometamol, the ED(50) for fentanyl was 5 fold lower than before: 3.8 +/- 1.1 microg kg(-1) and no significant recovery was observed 45 min later. The opioid antagonist naloxone (200 microg kg(-1)) did not reverse the effect, although in control experiments the same dose was able to prevent any action of fentanyl given alone. We conclude that the combination of fentanyl and subeffective doses of dexketoprofen trometamol induces a more potent and longer lasting analgesic effect than that observed with fentanyl alone, and that this is not an opioid mediated action.

Analgesics↗
PubMed2007

Mechanism-based PK/PD modeling of the respiratory depressant effect of buprenorphine and fentanyl in healthy volunteers.

The objective of this study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of buprenorphine and fentanyl for the respiratory depressant effect in healthy volunteers. Data on the time course of the ventilatory response at a fixed P(ET)CO(2) of 50 mm Hg and P(ET)O(2) of 110 mm Hg following intravenous administration of buprenorphine and fentanyl were obtained from two phase I studies (50 volunteers received buprenorphine: 0.05-0.6 mg/70 kg and 24 volunteers received fentanyl: 0.075-0.5 mg/70 kg). The PK/PD correlations were analyzed using nonlinear mixed effects modeling. A two- and three-compartment pharmacokinetic model characterized the time course of fentanyl and buprenorphine concentration, respectively. Three structurally different PK/PD models were evaluated for their appropriateness to describe the time course of respiratory depression: (1) a biophase distribution model with a fractional sigmoid E(max) pharmacodynamic model, (2) a receptor association/dissociation model with a linear transduction function, and (3) a combined biophase distribution-receptor association/dissociation model with a linear transduction function. The results show that for fentanyl hysteresis is entirely determined by the biophase distribution kinetics, whereas for buprenorphine hysteresis is caused by a combination of biophase distribution kinetics and receptor association/dissociation kinetics. The half-time values of biophase equilibration (t(1/2, k(eo))) were 16.4 and 75.3 min for fentanyl and buprenorphine, respectively. In addition, for buprenorphine, the value of k(on) was 0.246 ml/ng/min and the value of k(off) was 0.0102 min(-1). The concentration-effect relationship of buprenorphine was characterized by a ceiling effect at higher concentrations (intrinsic activity alpha=0.56, 95% confidence interval (CI): 0.50-0.62), whereas fentanyl displayed full respiratory depressant effect (alpha=0.91, 95% CI: 0.19-1.62).

Adult↗
PubMed1998

The effect of low-dose ketamine on fentanyl-induced respiratory depression.

This study evaluated if adding low-dose ketamine to fentanyl could offer a haemodynamically stable drug combination with little respiratory side-effects. Eight healthy, consenting male volunteers received in a random, cross-over and double-blind fashion both fentanyl 2 micrograms.kg-1 + ketamine 0.25 mg.kg-1 and fentanyl 2 micrograms.kg-1 + placebo. The fentanyl and placebo reduced minute ventilation, alveolar ventilation and oxygen consumption (p < 0.05), with little effect on haemodynamics. After fentanyl and ketamine, the decrease in minute ventilation and alveolar ventilation was attenuated compared to the placebo-containing combination (p < 0.05), but with a simultaneous increase in oxygen consumption (p < 0.05) and stimulation of haemodynamics (p < 0.05). Both treatments decreased oxygen saturation and arterial oxygen pressure similarly. Ketamine thus attenuated the fentanyl-induced reduction in ventilation without preventing the decrease in blood oxygenation. In conclusion, combining low-dose ketamine to fentanyl offers no benefits in terms of preventing respiratory depression.

Adult↗
PubMed2000

Pharmacokinetics of transdermal fentanyl in the peri-operative period in young children.

The pharmacokinetics of transdermal fentanyl were assessed in eight children aged 18-60 months, weighing 11-20 kg and monitored postoperatively in the intensive care unit. A patch, delivering 25 microg.h-1 of fentanyl, was applied for 72 h from the induction of anaesthesia. Plasma fentanyl concentrations were measured over 144 h. Mean (SD) peak concentration of fentanyl was 1.7 (0.66) ng.ml-1 and time to reach maximal plasma concentration was 18 (11) h. The elimination half-life was 14.5 (6.2) h, and the area under the curve for plasma fentanyl concentration (0-144 h) was 86.8 (27) ng.h.ml-1. Maximal fentanyl concentration was negatively correlated with patient age (r = - 0.71; p = 0.049) but not with body weight. These results suggest that the pharmacokinetics of transdermal fentanyl in children are similar to those in adults.

Administration, Cutaneous↗
PubMed2001

Adenotonsillectomy in children: a comparison of morphine and fentanyl for peri-operative analgesia.

This study compared the effectiveness and side-effects of intra-operative fentanyl with fentanyl and morphine for elective adenotonsillectomy in a double-blind study, in 60 children randomly allocated to receive either intravenous fentanyl 1 microg x kg(-1) intra-operatively or intramuscular morphine 100 microg x kg(-1) at induction. All children received a standard anaesthetic induction with intravenous fentanyl 1 microg x kg(-1) and propofol 4-5 mg x kg(-1) and maintenance with oxygen, nitrous oxide and isoflurane. Pain scores, emetic episodes and supplemental morphine requirements were recorded for 24 h postoperatively. The overall incidence of postoperative vomiting was high in both groups: 70% in the fentanyl group and 78% in the morphine group. The incidence of postoperative vomiting was lower in the fentanyl group (p < 0.03) in the first 4 h, but similar by 24 h. Children who received morphine at any time in the first 24 h had more median (range) episodes of vomiting [2 (0-7)] than children receiving fentanyl only [l (0-3); p < 0.03]. Administration of rescue anti-emetics, pain scores in recovery and pain scores over the next 24 h were similar between the two groups.

Adenoidectomy↗
PubMed1999

Evaluation of the electroencephalographic bispectral index during fentanyl-midazolam anaesthesia for cardiac surgery. Does it predict haemodynamic responses during endotracheal intubation and sternotomy?

The bispectral index, a value derived from the electroencephalogram, has been proposed as a measure of anaesthetic effect. The aim of the present study was to evaluate the bispectral index during midazolam-fentanyl anaesthesia for cardiac surgery for its possible role as a predictor of increases in systolic blood pressure during endotracheal intubation and sternotomy. After institutional approval 15 consenting patients, scheduled for elective cardiac surgery, were selected for the study. Anaesthesia was induced in all patients with a loading dose of fentanyl 7.5-10 micrograms kg-1, midazolam 0.15 mg kg-1 and pancuronium 0.1 mg kg-1. After a further bolus dose of fentanyl 10-12.5 micrograms kg-1 prior to the start of incision and sternotomy, maintenance infusion rates of fentanyl 4-6 micrograms kg-1 h-1 and midazolam 0.1 mg kg-1 h-1 were started and continued through surgery at the discretion of the anaesthetist and guided by the presenting clinical and haemodynamic responses. The control of anaesthesia was never based on the value of the bispectral index. The mean bispectral index value decreased from 95.7 (3.1) at base-line to 59.5 (12.0) after induction of anaesthesia and then remained below 70 throughout surgery. However, there was an important interindividual variability in bispectral index values despite standardized dosages of fentanyl and midazolam. There was no significant correlation between the bispectral index values in the pre-intubation and pre-incision period and the changes in systolic blood pressure during endotracheal intubation and sternotomy, respectively. In conclusion, the large intersubject variability in the bispectral index values should be investigated further in the light of the great variability in the clinical effects of midazolam and fentanyl. The lack of significant correlation between the bispectral index values and the haemodynamic responses suggest that the bispectral index, which is a helpful monitor of anaesthetic depth, is not a very reliable monitor of global anaesthetic adequacy during total intravenous anaesthesia with a combination of midazolam and fentanyl in cardiac surgical patients.

Adjuvants, Anesthesia↗
PubMed1997

Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium.

This study was conducted to examine the effect of cardiopulmonary bypass surgery on the total and unbound plasma concentrations of fentanyl and the total plasma concentrations of alcuronium. Total fentanyl concentrations were measured by gas chromatography, the plasma protein binding of fentanyl by ultrafiltration, and alcuronium concentrations by high-performance liquid chromatography. Sixteen patients were studied. On initiation of cardiopulmonary bypass (CPB), there were mean decreases of 58.8 +/- 7.1% and 47 +/- 3.2% for total concentrations of fentanyl in plasma and haemoglobin in blood, respectively. The magnitude of these reductions in individual patients was significantly related (Spearman p = 0.65, P < 0.05). The unbound fraction of fentanyl rose from 0.23 to 0.34 after the start of CPB. The total fentanyl concentration remained relatively stable during bypass until near the end of CPB when the mean total concentration increased, coinciding with rewarming. The size of the increase was related to the body mass index (BMI) of the patient (Spearman p = 0.85, P < 0.01). The estimated elimination half-life of fentanyl using the grouped data was 4.7 h. The total alcuronium concentration in plasma fell by 29% on initiation of CPB and there was no increase on rewarming. The estimated elimination half-life of alcuronium using the grouped data was 234 min. Despite marked declines in the plasma concentrations of both drugs on initiation of CPB, suitable levels of anaesthesia were maintained throughout the procedure.

Adjuvants, Anesthesia↗
PubMed2002

Cost analysis of fentanyl and remifentanil in coronary artery bypass graft surgery without cardiopulmonary bypass.

BACKGROUND: Opiates such as remifentanil have the potential to reduce time to extubation (TTE), shorten length of stay (LOS) and lower hospital costs, because of a short duration of action. However, the cost of remifentanil is approximately ten times higher than longer-acting opiates like fentanyl. OBJECTIVES: The objective of this analysis was to compare TTE, LOS and total hospital costs between patients who received remifentanil and fentanyl during off-pump bypass surgery. METHODS: The study was prospective and observational in design. Consecutive patients who underwent off-pump cardiac bypass surgery and received either remifentanil or fentanyl from September 1998 to August 1999 were screened for study entry. Patient bills and charges were converted to costs using hospital cost-to-charge ratios. The percent of patients' extubated in the operating room (OR), LOS and hospital costs were compared between the groups. RESULTS: The baseline demographics (age: 66 +/- 12 years mean +/- SD; female 36%) and intraoperative variables were similar between the remifentanil (n=39) and fentanyl (n=20) groups. Patients given remifentanil during surgery were significantly more likely to be extubated in the OR than patients given fentanyl (15 vs. 64%; P < 0.001). Mean LOS was similar in both groups (7.3 +/- 3.1 vs. 8.3 +/- 2.7 days; P=0.27). Patients who received remifentanil incurred lower pulmonary function testing ($0 +/- 0 vs. $34 +/- 103; P=0.045), recovery room ($31 +/- 40 vs. $65 +/- 33; P=0.002) and lower ward costs ($3973 +/- 1719 vs. $4808 +/- 1794; P=0.09) than patients who received fentanyl. Anesthesia costs were higher among patients who received remifentanil ($476 +/- 102 vs. $416 +/- 130; P=0.06). Medical and surgical supplies, OR, intensive care unit, laboratory, respiratory therapy, pharmacy, radiology and transfusion costs were similar between the two groups. The total cost was $15 272 +/- 5556 and $15 616 +/- 4169 in the remifentanil and fentanyl groups, respectively (P=0.81). CONCLUSION: Remifentanil, when used in off-pump bypass surgery, is associated with an increased likelihood of extubation in the OR. However, LOS and total hospital costs remain unchanged.

Aged↗
PubMed2002

Intranasal fentanyl reduces acute pain in children in the emergency department: a safety and efficacy study.

INTRODUCTION: Provision of rapid, painless and effective analgesia to children remains problematic in the prehospital and emergency setting. Intranasal fentanyl has the potential to eliminate many of the problems of narcotic administration in children. The aim of this study, conducted in a tertiary paediatric emergency department was to evaluate the safety and efficacy of intranasal fentanyl in children. METHODS: Children in acute pain aged between three and 12 years inclusive were enrolled on presentation to the emergency department. Routine observations and pain scoring by the child and caregiver was undertaken prior to the child receiving fentanyl (20 micrograms for 3-7 year olds and 40 micrograms for 8-12 year olds) and at intervals of 5 min for 30 min Additional fentanyl at the dose of 20 micrograms was given 5 minutely as required. Caregivers and older children used a visual analogue scale (VAS) and the younger children used the Wong-Baker faces scale (WBS). RESULTS: Forty five children were enrolled with a mean age of 8.0 years. The median dose of fentanyl administered was 1.5 micrograms/kg. Mean pain score in 32 children using the VAS was 62.3 mm (95% confidence interval 53.2-69.4 mm) at presentation and reduced at 10 min to 44.6 mm (95% confidence interval 36.2-53.1 mm). In 16 children using WBS the initial mean reading was 4.0 (95% confidence interval 3.3-4.7) and reduced to 2.2 (95% confidence interval 1.3-3.1) at 10 min. Caregiver pain scores showed a mean preintervention pain score of 64.9 mm (95% confidence interval 57.7-72.2 mm) with a significant reduction at 10 min to 41.7 mm (95% confidence interval 34.7-48.6 mm). There was no significant alteration in pulse rate, respiratory rate, and blood pressure or oxygen saturations. There were no negative side-effects. CONCLUSIONS: Early and significant reduction in pain (compared to baseline assessments) was achieved in children using intranasal fentanyl by 10 min and sustained throughout the 30 min of observations. This raises the possibility of using intranasal fentanyl in children in the prehospital setting as well as a role for this form of analgesia as triage nurse-initiated administration in the emergency department.

Administration, Intranasal↗
PubMed2003

Dermal penetration of fentanyl: inter- and intraindividual variations.

Fentanyl is a potent synthetic opioid that is increasingly being used in transdermal drug delivery systems. The target organ concentration of a drug administered dermally will depend on the rate of dermal absorption and the systemic elimination. We have studied the intra- and interindividual variation in dermal penetration of fentanyl in an in vitro model (static diffusion cells) with human skin, and compared the absorption of fentanyl from an aqueous solution with absorption from a commercial patch. The intraindividual variation in dermal penetration of fentanyl in aqueous solution was limited (18%) and no differences in penetration characteristics were observed between breast and abdominal skin. The interindividual variation in dermal penetration of fentanyl was extensive, with maximal fluxes ranging from 21-105 ng/cm2/hr following application of an infinite dose of fentanyl to the donor chamber. Use of transdermal drug delivery systems (patches) reduced the inter-individual variation. The permeability coefficients after application of fentanyl in aqueous solution and through patches were identical (0.0011 cm/hr). One person had a higher than average penetration rate following patch application, which may indicate that the human skin and not the patch barrier was the rate-determining factor for the other individuals included in this study.

Administration, Cutaneous↗
PubMed2002

Transdermal fentanyl for the management of acute pancreatitis pain.

Although the hazards of using Demerol for pain management is well documented, physicians at a 350-bed tertiary-care center in the upper midwest continued to follow the antiquated practice of ordering intramuscular Demerol and Vistaril to manage pain for patients with acute pancreatitis. Their reasoning was based on early evidence that Demerol, unlike morphine, does not cause biliary-tract spasms resulting in epigastric or right upper quadrant pain. In an effort to change practice patterns, a multidisciplinary team was formed to study the efficacy of using Transdermal Therapeutic System (TTS) fentanyl to manage pain in this patient population. Thirty-two subjects were enrolled in a double-blind, placebo-controlled study to evaluate the efficacy of using TTS fentanyl with intramuscular Demerol for breakthrough pain in comparison to using a placebo system and intramuscular Demerol. There was no statistically significant difference in self-reported pain intensity between the control and experimental groups on the first day of hospitalization. This finding would be expected because serum fentanyl concentrations rise gradually during the first 12 to 14 hours after application of the TTS fentanyl and plateau at 24 hours. There was a statistically significant difference between groups at 36 hours (exact p <.0154) and 45 hours (exact p <.0132) after application of the TTS fentanyl. This is probably because of greater serum fentanyl concentrations observed during the 36- to 48-hour period after application of TTS fentanyl. Although not statistically significant, trends in the data revealed that the experimental group had lower self-reported pain intensity scores than the control group throughout the course of hospitalization. Even though the experimental group had significantly more previous hospitalizations for acute pancreatitis and a higher pain intensity score on admission, this group had a significantly shorter length of stay in the hospital c2 (1, N = 31) = 4.3706 p <.05. There was no statistically significant difference between the two groups for self-reported satisfaction with pain management.

Abdominal Pain↗
PubMed2005

pKa of fentanyl varies with temperature: implications for acid-base management during extremes of body temperature.

OBJECTIVE: The pKa of fentanyl has not been measured previously at varying extremes of body temperature. The goal of this laboratory investigation was to test the hypothesis that the pKa of fentanyl changes with temperature. DESIGN: The investigation involved measuring the pKa values of aqueous fentanyl at varying temperatures. SETTING: The investigation was conducted in a controlled laboratory environment. PARTICIPANTS: No human or animal subjects were involved. INTERVENTIONS: Because no live subjects were involved in the investigation, no interventions were necessary. MEASUREMENTS AND MAIN RESULTS: This paper reports the effect of temperature on the pKa of fentanyl. The pKa of aqueous fentanyl was measured at 15 degrees C, 25 degrees C, 37 degrees C, 42 degrees C, and 47.5 degrees C by potentiometric titration in 0.01 mmol/L of potassium chloride after extensive degassing. Data were analyzed using the least squares method with an appropriately fitting equation. The pKa of fentanyl was found to change in a similar manner to the neutral point of water at varying temperatures. CONCLUSIONS: This finding has implications for the bioavailability of fentanyl at extremes of body temperature in association with the clinical acid-base management of the patient. Clinical implications for differing methods of intraoperative acid-base management at varying temperatures are discussed.

Acid-Base Equilibrium↗
PubMed2005

The mechanisms of the direct vascular effects of fentanyl on isolated human saphenous veins in vitro.

OBJECTIVE: The purpose of this study was to determine the mechanism of the direct effects of fentanyl on human veins in vitro. DESIGN: In vitro, prospective with repeated measures. SETTING: University research laboratory. INTERVENTIONS: Dose-response curves were obtained for cumulative doses of fentanyl (10(-9)-10(-5) mol/L) on saphenous vein strips precontracted with (10(-6) mol/L) 5-hydroxytryptamine incubated with either naloxone (10(-4) mol/L), Nomega-nitroL-arginine-methyl ester (L-NAME) (10(-4) mol/L), indomethacin (10(-5) mol/L), glibenclamide (10(-4) mol/L), tetraethylammonium (10(-4) mol/L), or ouabain (10(-5) mol/L). Vein strips were also exposed to a Ca++-free solution and 0.1 mmol/L of ethylene glycol-bis-(b-aminoethylether) N,N'-tetraacetic acid; 5-hydroxytryptamine (10(-6) mol/L) was added to the bath before cumulative Ca++ (10(-4)-10(-2) mol/L). The same procedure was repeated in the presence of fentanyl (10(-6) , 3 x 10(-6) , or 10(-5) mol/L) (p < 0.05 = significant). MEASUREMENTS AND MAIN RESULTS: Preincubation of vein strips with naloxone, L-NAME, or indomethacin did not influence the relaxant responses to fentanyl (p > 0.05). Tetraethylammonium, glibenclamide, and ouabain reduced the relaxation response to fentanyl (p < 0.05). A stepwise increase in tension was recorded with cumulative doses of Ca++ (p < 0.05). CONCLUSIONS: The present results show that fentanyl causes vasodilatation via both endothelium- and opioid receptor-independent mechanisms in the human saphenous vein. The relaxant effects of fentanyl are probably via activation of K+ channel and Na+K+-adenosine trisphosphatase and inhibition of Ca++ channel.

Analgesics, Opioid↗