Intravenous Bolus Of Fentanyl Research Articles

Femoral and sciatic nerve blockade of the pelvic limb with and without obturator nerve block for tibial plateau levelling osteotomy surgery in dogs

ObjectiveTo determine the effect of blocking the obturator nerve in addition to performing femoral nerve and sciatic nerve blocks on intraoperative nociception in dogs undergoing unilateral tibial plateau levelling osteotomy (TPLO) surgery. Study designProspective, blinded, randomized, placebo-controlled, clinical comparison. AnimalsA total of 88 client-owned dogs undergoing unilateral TPLO surgery (100 procedures). MethodsDogs were randomly assigned to either group FSO (femoral, sciatic and obturator nerve blocks) [n = 50; ropivacaine 0.75% (0.75 mg kg–1)] or group FSP (femoral, sciatic and placebo) [n = 50; ropivacaine 0.75% (0.75 mg kg–1) femoral and sciatic nerve blocks plus saline solution 0.9% (0.1 mL kg–1) as a placebo injection around the obturator nerve]. The anaesthetic protocol was standardized. Data collection included intraoperative cardiopulmonary variables and opioid consumption. Rescue analgesia consisted of an intravenous bolus of fentanyl (2 μg kg–1) and was administered when a change in cardiopulmonary variables (20% increase in mean arterial pressure or heart rate) was attributed to a sympathetic stimulus. Data were analysed using generalized linear mixed models, cross tables and multivariable binary logistic regression. Results were expressed as adjusted odds ratios with 95% confidence intervals and Wald p values (α = 0.05). ResultsThere were no clinically relevant differences between groups in intraoperative cardiopulmonary variables and need for rescue analgesia. The requirement for rescue analgesia was significantly higher in dogs with a body weight >34 kg. Conclusions and clinical relevanceAnaesthesia of the obturator nerve in addition to the femoral and sciatic nerves was not associated with clinically significant differences in cardiopulmonary variables or a reduced need for rescue analgesia. Therefore, the clinical benefit of an additional obturator nerve block for intraoperative antinociception in dogs undergoing unilateral TPLO surgery using the described anaesthetic regimen is low.

A prospective observational study on the feasibility of subumbilical laparoscopic procedures under epidural anesthesia in sedated spontaneously breathing infants with a natural airway.

BackgroundLaparoscopic procedures are usually performed under general anesthesia with a secured airway including endotracheal intubation or supraglottic airways.AimsThis is a prospective study of the feasibility of subumbilical laparoscopic procedures under epidural anesthesia in sedated, spontaneous breathing infants with a natural airway.MethodsWe consecutively enrolled 20 children <3 years old with nonpalpable testes scheduled for diagnostic laparoscopy with or without an ensuing orchidopexy, inguinal revision, or Fowler‐Stephens maneuver. Inhalational induction for venous access was followed by sedation with propofol and ultrasound‐guided single‐shot epidural anesthesia via the caudal or thoracolumbar approach using 1.0 or 0.5 ml kg−1 ropivacaine 0.38%, respectively. The primary outcome measure was block success, defined as no increase in heart rate by >15% or other indicators of pain upon skin incision.ResultsOf the 20 children (median age: 10 months; IQR: 8.3−12), 17 (85%) were anesthetized through a caudal and 3 (15%) through a direct thoracolumbar epidural, 18 (90%) underwent a surgical procedure and 2 (10%) diagnostic laparoscopy only. Five patients (25%) received block augmentation using an intravenous bolus of fentanyl (median dose: 0.9 µg kg−1; IQR: 0.8−0.95) after the initial prick test and before skin incision. There was no additional need for systemic pain therapy in the operating theater or recovery room. No events of respiratory failure or aspiration were observed.ConclusionsIn experienced hands, given our success rate of 100%, epidural anesthesia performed in sedated spontaneously breathing infants with a natural airway can be an alternative strategy for subumbilical laparoscopic procedures.

A randomized control trial on comparative effect of scalp nerve block using levobupivacaine versus fentanyl on the attenuation of pain and hemodynamic response to pin fixation

Background: The application of head fixation device and tightening of the pins on the scalp acts as an intense noxious stimulus with an increased hemodynamic response. We aimed at comparing the efficacy of scalp nerve block (SNB) using levobupivacaine against intravenous fentanyl bolus dose followed by continuous intravenous infusion for attenuation of pain and hemodynamic response to pin fixation. Methods: One hundred and eight patients undergoing elective supratentorial craniotomy under general anesthesia were randomly allocated to two groups: Group F received a bolus of intravenous fentanyl (2 μg/kg) followed by continuous maintenance infusion and Group S, in which a bilateral SNB was performed with 20 ml of 0.5% levobupivacaine. Hemodynamic variables and pain scores were the primary outcomes noted. Intraoperative isoflurane and additional fentanyl requirements, emergence time and any side effects were also recorded. Results: The variation in hemodynamics in terms of heart rate (per minute) at pin fixation (Group F [95.88 ± 7.79] and Group S [89.02 ± 5.42]) was significant (P

An allometric pharmacokinetic model and minimum effective analgesic concentration of fentanyl in patients undergoing major abdominal surgery

BackgroundWe aimed to characterise the population pharmacokinetics of fentanyl in adults and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of i.v. fentanyl in patients after major abdominal open surgery. MethodsIn the pharmacokinetic study, subjects received an intravenous bolus of fentanyl 100 μg during operation, and arterial blood was sampled at pre-set intervals. In addition, data from previously published fentanyl pharmacokinetic studies were incorporated to build a pharmacokinetic model. In the MEAC study, subjects were asked to rate their pain every 10 min using a VAS (0=no pain, 10=most severe pain) in the PACU. The first blood sample was obtained when wound pain was rated as ≥3 at rest or ≥5 during compression. Then, fentanyl 50 μg was administered every 10 min until the pain intensity had decreased to <3 at rest and <5 during compression, at which point the second blood was sampled and the first MEAC of fentanyl was measured. The same procedure was repeated to obtain a third sample (MEC) and a fourth sample (second MEAC). ResultsIn the population pharmacokinetic study (n=95), the plasma concentration of fentanyl over time was well-described by the three-compartment mammillary model using an allometric expression. The V1, V2, V3, Cl, Q1, and Q2 of a 70 kg subject were 10.1, 26.5, 206 L, 0.704, 2.38, and 1.49 L min−1, respectively. In the MEAC study (n=30), the median (inter-quartile range) MEC and MEAC were 0.72 (0.58–1.05) ng ml−1, and 0.99 (0.76–1.28) ng ml−1, respectively. ConclusionThese results provide a scientific basis for the use of fentanyl for acute postoperative pain management in surgical patients. Clinical trial registrationKCT0003273 (http://cris.nih.go.kr).

Effects of a single intravenous bolus of fentanyl on the minimum anesthetic concentration of isoflurane in chickens (Gallus gallus domesticus)

ObjectiveTo assess the temporal effects of a single fentanyl intravenous (IV) bolus on the minimum anesthetic concentration (MAC) of isoflurane in chickens and to evaluate the effects of this combination on heart rate (HR) and rhythm, systemic arterial pressures (sAP) and ventilation. Study designProspective experimental trial. AnimalsSeventeen adult chickens weighing 1.8±0.2 kg. MethodsIndividual isoflurane MAC for 17 chickens was previously determined using the bracketing method. Chickens were anesthetized with isoflurane to evaluate the effects of a single IV fentanyl bolus (10 or 30 μg kg−1) on isoflurane MAC over time using the up-and-down method. Ventilation was controlled. The isoflurane MAC reduction was estimated by logistic regression at 5 and 15 minutes after fentanyl administration. In the second phase, seven chickens were anesthetized with isoflurane, and fentanyl was administered (30 μg kg−1) IV over 1 minute during spontaneous ventilation and HR and rhythm, sAP and ventilation variables were measured. ResultsAt 5 minutes after IV administration of fentanyl (10 or 30 μg kg−1), isoflurane MAC was significantly reduced by 17.6% (6.1–29.1%) [logistic regression estimate (95% Wald confidence interval)] and 42.6% (13.3–71.9%), respectively. Isoflurane MAC reduction at 15 minutes after IV administration of fentanyl (10 or 30 μg kg−1) was 6.2% (−0.6 to 12.9%) and 13.2% (−0.9 to 27.3%), respectively; however, this reduction was not significant. No clinically significant cardiopulmonary changes or arrhythmias were detected after the administration of fentanyl (30 μg kg−1). Conclusions and clinical relevanceAdministration of a single fentanyl bolus induced a dose-dependent and short-lasting reduction in isoflurane MAC. The higher dose induced no significant cardiopulmonary depression in isoflurane-anesthetized chickens during spontaneous ventilation. In chickens anesthetized with isoflurane, the clinical usefulness of a single fentanyl bolus is limited by its short duration of effect.

Comparison of propofol and ketofol in minor gynecologic interventions

Objective: Outpatient anesthesia requires a safe anesthetic method and an anesthetic agent that provides a rapid anesthesia depth and hemodynamic stability. To provide an uneventfully recovery, the anesthetic must also be rapidly metabolized, and its metabolites should not accumulate in the body. This study compared sedo-analgesia effects, recovery times, postoperative complications, Modified Aldrete Scale, Visual Analog Scores, and patient and surgeon satisfaction between propofol and ketofol, administered as anesthetics during the probe curettage procedure. Methods: A total of 60 female patients included in the study. Group P was administered 2 mg/kg of propofol and a 1 μg/kg intravenous bolus of fentanyl for induction and 100 μg/kg/min of propofol for maintenance. Group K was administered a 600 µg/kg IV bolus of ketofol for induction and 100 µg/kg/min of ketofol for maintenance. Additional fentanyl (50 µg) was administered to Group P, and 25 µg/kg/min of ketofol was administered to Group K according to autonomic and hemodynamic responses. Results: Demographic data of the 2 groups were similar. A significant decrease in hemodynamic values was detected in patients in Group P after induction. No change in these values was detected during or after induction in Group K. The additional analgesia requirement was 66.6% in Group P. Nausea was detected in 2 patients in Group K. Additionally, hallucination was detected in 2 patients in Group K. Patient and surgeon satisfaction were complete in both groups. Conclusion: According to our findings, ketofol anesthesia may be a good option in uterine curettage, patients recover quickly and comfortably, and ketofol both provides sufficient analgesia for the minor surgical intervention and reduces complications. J Clin Exp Invest 2015; 6 (3): 244-250 Key words: Ketofol, propofol, sedo-analgesia, uterine curettage

Preemptive use of Small Dose Fentanyl Suppresses Fentanyl Induced Cough

Fentanyl, a synthetic opioid, is a popular choice amongst anaesthesiologists in the operating room. Pre induction intravenous fentanyl bolus is associated with coughing in 28-65% of patients. Fentanyl induced cough is not always benign and can be remarkably troublesome at the most critical moment of anaesthesia when airway reflex is lost. To study the effect of pre emptive use of minimal dose fentanyl through the peripheral venous cannulae on the incidence of cough by a larger bolus of intravenous fentanyl. One hundred and fifty patients aged 18-75 years undergoing elective surgical procedures were randomized into three groups of 50 each. The first group received 0.5 ml saline 0.9% intravenously one minute prior to the administration of fentanyl 150 μg (3 ml); the second group received pre emptive fentanyl 25 μg (0.5 ml) prior to the administration of fentanyl 125 μg (2.5 ml); and the third group received preemptive fentanyl 25 μg (0.5 ml), followed by the administration of fentanyl 150 μg (3 ml). Based on the number of coughs observed, cough severity was graded as mild (1-2), moderate (3-5), or severe (>5). The incidence of fentanyl induced cough was significantly lower in both pre emptive group 4 (8%) for 125 μg fentanyl and 7 (14%) for 150 μg than in the saline group 15 (30%). Pre-emptive use of minimal dose fentanyl 25 μg administered one minute before a larger bolus dose of fentanyl (125 or 150 μg) can effectively suppress cough.

Perioperative evaluation of tumescent anaesthesia technique in bitches submitted to unilateral mastectomy.

BackgroundTumescent anaesthesia (TA) is a widely used technique in oncologic surgeries necessitating large resection margins. This technique produces transoperative and postoperative analgesia, reduces surgical bleeding, and facilitates tissue divulsion. This prospective, randomised, blind study evaluated the use of TA in bitches submitted to mastectomy and compared the effect of TA with an intravenous fentanyl bolus. A 2.5-mcg/kg intravenous fentanyl bolus (n = 10) was compared with TA using 0.275% lidocaine (n = 10) in bitches submitted to unilateral mastectomy. Sedation was performed by intramuscular (IM) injection of 0.05 mg/kg of acepromazine combined with 2 mg/kg of meperidine. Anaesthesia was induced with 5 mg/kg of intravenous propofol and maintained with isoflurane/O2. Heart and respiratory rates; systolic, mean, and diastolic arterial blood pressures; central venous pressure; SpO2; ETCO2; inspired and expired isoflurane concentrations; and temperature were measured transoperatively. Visual analogue scales for sedation and pain and the Glasgow composite and Melbourne pain scales were used for postoperative assessment. The surgeon investigated the quality of the surgical approach, considering bleeding and resection ability, and the incidence of postoperative wound complications.ResultsThe heart rate was lower and the end-tidal isoflurane concentration was higher in dogs treated with fentanyl than in dogs treated with TA. A fentanyl bolus was administered to 8 of 10 dogs treated with fentanyl and to none treated with TA. Intraoperative bleeding and the mammary gland excision time were lower in dogs treated with TA. The maximal mean and individual plasma lidocaine concentrations were 1426 ± 502 ng/ml and 2443 ng/ml at 90 minutes after infiltration, respectively. The Glasgow Composite Pain Scale scores were higher in dogs treated with fentanyl than in dogs treated with TA until 2 hours after extubation.ConclusionsCompared with intravenous fentanyl, TA in bitches: may be easily performed in non-inflamed, ulcerated, adhered mammary tumours; has an isoflurane-sparing effect; improves transoperative and immediate postoperative analgesia; is apparently safe for use in clinical conditions as evidenced by the fact that it did not produce any adverse signs or lidocaine plasma concentrations compatible with toxicity; does not modify the recovery time; and facilitates the surgical procedure without interfering with wound healing.

Priming dose of intravenous rocuronium suppresses fentanyl-induced coughing

ObjectivesAn intravenous bolus of fentanyl often induces a cough reflex. This study investigates whether priming with rocuronium can effectively attenuate fentanyl-induced coughing. MethodsThe study involved 260 participants, aged between 18 and 80 years of age, who were undergoing various elective surgeries. They were randomly assigned to two groups. Patients in the study group (the rocuronium group) were treated with intravenous (IV) 0.06 mg/kg rocuronium, whereas those in the control group were treated with the same volume of normal saline. Fentanyl (1.5 μg/kg IV, given over 2 seconds) was administered 30 seconds after the injection of rocuronium or normal saline. We recorded the number of coughs for 1 minute after the fentanyl injection. ResultsPatients in the rocuronium group showed a significantly lower incidence of coughing (8.5% vs. 23.1%, in the control group; p < 0.05) and a milder severity of cough in comparison with the patients in the control group. ConclusionPretreatment with IV rocuronium (0.06 mg/kg) suppressed the cough reflex induced by fentanyl. Therefore, priming with rocuronium may be a clinically useful method for preventing fentanyl-induced cough.

Lidocaína com vasoconstrictor isolada e associada ao fentanil via peridural em cães

O objetivo deste estudo cego foi avaliar os efeitos cardiorrespiratórios e analgésicos de diferentes doses de fentanil associado à lidocaína com vasoconstrictor via peridural em cães. Foram avaliados 28 cães adultos, distribuídos em quatro tratamentos: 5mg kg-1 de lidocaína isolada (L) e associada ao fentanil nas doses de 2,5, 5 e 7mg kg-1 (F2,5, F5 e F7, respectivamente). Quinze minutos antes da punção peridural, todos os animais foram tranquilizados por via intravenosa (IV) com acepromazina (0,05mg kg-1), além de um bolus (IV) de fentanil (2,5mg kg-1), administrado imediatamente antes da injeção peridural. Foram avaliados: frequência cardíaca (FC), eletrocardiograma (ECG), pressão arterial sistólica (PAS), frequência respiratória (f), gases sanguíneos, período de latência, duração e extensão do bloqueio sensitivo. Houve redução da FC após a anestesia peridural em relação ao basal em F2,5, F5 e F7. A FC foi superior no L em relação ao F5 e F7 aos 30 e 60 minutos após a anestesia peridural. O período de latência não variou entre os grupos, enquanto a duração do bloqueio foi superior no F5. Bloqueio sensitivo até a 6ª vértebra lombar foi observado em quatro animais no L. Bloqueio sensitivo até a 1ª vértebra lombar foi observado em cinco cães no F2,5 e F7 e em seis cães no F5. Conclui-se que a adição do fentanil à lidocaína determinou bloqueio sensitivo mais cranial em relação ao uso isolado desse anestésico local. Paralelamente, bloqueio anestésico mais duradouro foi determinado pela adição de 5mg kg-1 de fentanil à lidocaína em relação aos demais tratamentos.

Comparison of Liquid Chromatography-Mass Spectrometry and Radioimmunoassay for Measurement of Fentanyl and Determination of Pharmacokinetics in Equine Plasma

This study evaluated the validity of measuring fentanyl concentrations in equine plasma using radioimmunoassay (RIA) by comparing it to the established technique of liquid chromatography-mass spectrometry (LC-MS). Equine plasma samples were analyzed using a solid-phase Coat-A-Count fentanyl RIA and a validated LC-MS method. The fentanyl concentrations derived by both methods were compared by linear regression and pharmacokinetic analysis. The cross-reactivity of the primary equine fentanyl metabolite, N-[1-(2-phenethyl-4-piperidinyl)]maloanilinic acid (PMA), with the RIA was determined. The binding potency of fentanyl and PMA were compared at three opioid receptor subtypes in equine cerebral cortex using a radioligand binding technique. Fentanyl concentrations determined by RIA and LC-MS correlated, but the RIA overestimated low fentanyl concentrations and underestimated high fentanyl concentrations. The overestimation of low fentanyl concentrations is most likely due to the 29% cross-reactivity of PMA with the RIA. As a result, pharmacokinetic variables determined from an intravenous fentanyl bolus to four anesthetized horses differed depending on the analytical method. Although fentanyl bound with nanomolar potency to the three receptor subtypes, PMA exhibited no binding activity even at micromolar concentrations. In conclusion, when compared with LC-MS, fentanyl concentrations determined by RIA in equine plasma are misleading, especially for the calculation of fentanyl pharmacokinetics.

Adjustable Strabismus Surgery under Intravenous Anesthesia with Propofol and Fentanyl

Purpose: To evaluate the clinical usefulness of intravenous propofol and fentanyl anesthesia during adjustable strabismus surgery, to investigate the effectiveness and safety of adjustable strabismus surgery, and assess the degree of patient satisfaction. Methods: Patients over 15 years of age who underwent strabismus surgery using propofol and fentanyl sedation from January 2003 to December 2004 were included in this study. At the beginning of the operation, the patients received an intravenous bolus of fentanyl 1 to 1.5 mg/kg. Propofol was injected into a vein continuously during the operation to keep the blood concentration within 1.2-1.5 ug/mL. Intraoperative adjustment was then made. We evaluated, via questionnaire, patient satisfaction with the operation and the adjustment. Results: In all 44 patients, the adjustment was completed successfully. The rate of intraoperative side effects was low (11.4%). The satisfaction degree regarding the anesthesia was very high (95.5%), and the success rate at the three-month postoperative visit was 88.6%. Conclusions: Intravenous anesthesia using propofol combined with fentanyl provides a sufficient level of sedation and rapid awakening that enables a surgeon to perform adjustable strabismus surgery conveniently. It also allows the patient to feel comfortable and safe throughout the surgery.

Pre‐medication with intravenous clonidine suppresses fentanyl‐induced cough

A reflex cough is often observed after an intravenous bolus of fentanyl. This study was conducted to determine whether pre-treatment with intravenous clonidine could effectively attenuate fentanyl-induced cough. Three hundred ASA I-II patients, aged between 18 and 80 years, undergoing various elective surgeries, were enrolled in this study. All patients were randomly assigned to one of two groups treated with intravenous clonidine 2 microg/kg (clonidine group) or the same volume of normal saline (control group). Intravenous fentanyl (2 microg/kg in 2 s) was injected 2 min after the clonidine or normal saline injection. Changes in the hemodynamics, auditory evoked potentials (AEPs) and Observer Assessment of Alertness/Sedation (OAA/S) rating scale were recorded before and 2 min after the clonidine or normal saline injection and 1 min after the fentanyl injection. The number of coughs 1 min after the fentanyl injection was also recorded. Patients in the clonidine group showed a significantly lower incidence of cough than those in the control group (17.3% vs. 38.7%, respectively; P < 0.01). The blood pressure was lower in the clonidine group than in the control group. There were no significant differences in AEP or OAA/S rating scale. Pre-treatment with intravenous clonidine (2 microg/kg) suppressed the reflex cough induced by fentanyl, with mild hemodynamic changes. Therefore, intravenous clonidine may be a clinically useful method of suppressing fentanyl-induced cough.

Effects of fentanyl on pain and hemodynamic response after retrobulbar block in patients having phacoemulsification

Purpose To determine the effects of systemic fentanyl analgesia in preventing the pain related to the administration of retrobulbar anesthesia and cataract surgery. Setting Departments of Ophthalmology and Anesthesiology, School of Medicine, Kocatepe University, Afyon, Turkey. Methods One hundred twenty patients with American Society of Anesthesiologists physical status I to III scheduled for cataract surgery were evaluated in a single-blind randomized study. Patients with a history of hypertension, hyperthyroidism, or neurologic or psychiatric disorders were excluded. In the study (fentanyl) group, an intravenous bolus of fentanyl 2 μg/kg was slowly given 5 minutes before retrobulbar anesthesia was administered. In the control group, fentanyl was not given. There were 60 patients in each group. Demographic data were not statistically different between the 2 groups. The intensity of pain during injection and intraoperatively was measured by verbal pain scores. Hemodynamic stability was assessed by the heart rate (HR) and mean arterial pressure (MAP). End-tidal carbon dioxide concentrations and oxygen saturations were also recorded. Results The changes in HR and MAP at 0, 10, 20, and 30 minutes were statistically significant between the fentanyl and control groups ( P<.05). Fentanyl reduced pain scores significantly at all evaluations ( P<.05). Conclusion The results suggest that fentanyl preemptively decreases injection and intraoperative hyperalgesia and provides hemodynamic stability without affecting patient cooperation, resulting in cataract surgery with retrobulbar anesthesia that is comfortable for both surgeon and patient.

Age related prolactin secretion in men after fentanyl anaesthesia

The aim of this study was to investigate the role of age in the hormonal response to opiate anaesthetic fentanyl. In 90 patients undergoing aortocoronary bypass, 59.6±9.2 years mean age, 35–81 age range, prolactin (PRL), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH), human growth hormone (HGH), insulin-like growth factor I (IGF I), glucagon and insulin were measured in venous blood samples drawn from fasting patients immediately before, at 8 h in the morning, and 60 min after the induction of anaesthesia with 30 μg/kg intravenous fentanyl bolus, 30 min after a second 7 μg/kg fentanyl bolus. Results showed a higher 60 min PRL peak in older, >65 years, in respect to younger, ≤50 years, patients (57.6±23.3 vs. 40.6±13.8 μg/l, P<0.005), with a significant upward trend with age across the entire age span ( r=0.32; P<0.002), while no difference by age was found for the basal concentrations. No differences were found between the respective basal and 60 min concentrations for the other hormones investigated. As expected, differences by age were found for FSH, higher in >65 and in 51–65-year-olds than in younger patients (for the basal values, respectively, P<0.02 and P<0.05); IGF I was lower in >65 in respect to≤50 ( P<0.02) and to 51–65-year-old patients ( P<0.05), with a significant negative correlation with age ( r=−0.33; P<0.005). The study shows an age related increase of PRL concentrations after fentanyl administration. It may be due to the reduction of the hypothalamic dopaminergic tone with aging. IGF I levels have been confirmed to be inversely correlated with age.

A review of the use of fentanyl analgesia in the management of acute pain in adults.

A review of the use of fentanyl analgesia in the management of acute pain in adults.

Placental transfer of fentanyl in early human pregnancy.

To investigate the transfer of fentanyl across the early human placenta, we have collected samples of maternal blood and fetal fluids and/or blood, simultaneously, between 5 and 22 min following an intravenous bolus of fentanyl (1.5 microg/kg) to the mother. The pregnancies were between 6 and 16 weeks of gestation and scheduled for elective termination of pregnancy under general anaesthesia. Total fentanyl concentration was determined by radioimmunoassay in 11 pairs of first trimester maternal serum and fetal coelomic fluid samples, 14 pairs of maternal serum and amniotic fluid samples, seven series of first trimester maternal serum and coelomic and amniotic fluid samples, and 10 series of early second trimester maternal and fetal sera and amniotic fluid samples. Fentanyl was not detected in coelomic fluid samples at any gestational age and in amniotic fluid samples collected after 12 weeks of gestation. Measurable concentrations of fentanyl were found in maternal serum collected within 15 min after the initial bolus and in fetal serum collected between 10 and 12 min later. These findings indicate that fentanyl is transferred across the early placenta into the amniotic cavity and fetal blood circulation but not into the exocoelomic cavity. The distribution of this molecule inside the early gestational sac is probably influenced by the increased binding by maternal and fetal sera, its short half-life of distribution and the specific biology of the fetal fluid formation and composition.

The Effect of Skull-Pin Insertion on Cerebrospinal Fluid Pressure and Cerebral Perfusion Pressure

This randomized prospective study measured the effects of an intravenous opioid bolus on cerebrospinal fluid pressure (CSFP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) during skull-pin insertion. Twenty-two adult patients scheduled for elective craniotomy for supratentorial lesions were studied. Outcome variables were MAP, heart rate (HR), and lumbar CSFP. The standardized anesthetic egimen included fentanyl (2 micro g/kg), thiopental (5-7 mg/kg), lidocaine (1.5 mg/kg), isoflurane (0.3-0.7 minimum alveolar anesthetic concentration), and vecuronium (0.1 mg/kg). During stable anesthesia, sufentanil (0.8 micro g/kg) or fentanyl (4.5 micro g/kg) was given as a bolus before skull-pin insertion. The hemodynamic effects of the opioid injection were modified with phenylephrine and/or atropine when indicated. CSFP remained unchanged in both treatment groups. MAP and CPP increased approximately 10 mm Hg after skull-pin insertion (P<0.001). In the sufentanil group, HR decreased approximately 10 bpm after opioid injection and remained decreased throughout the study. In fentanyl-treated patients, HR decreased 8 bpm after opioid injection but returned to preopioid rates after skull-pin insertion. In conclusion, in anesthetized patients, an intravenous bolus of fentanyl or sufentanil prior to skull-pin insertion results in stable values of CSFP, CPP, BP, and HR when the hemodynamic effects of the opioid are modified with phenylephrine and atropine. (Anesth Analg 1997;84:1292-6)

Human Brain Activity Response to Fentanyl Imaged by Positron Emission Tomography

Positron emission tomography (PET) is a noninvasive imaging technique that can be used to observe drug actions on human brain in vivo.We used15 O-water PET scanning in six volunteers to examine the effects on regional cerebral activity as reflected by regional cerebral blood flow (rCBF) of a small intravenous bolus of fentanyl. rCBF was compared between scans obtained after fentanyl or a placebo using three separate statistical criteria including a pixel-by-pixel t statistic; significance was stringently defined at P values < 0.01. Anatomic locations of regional cerebral activity changes were verified by aligning rCBF PET scans with cranial magnetic resonance images using mathematical coregistration. Fentanyl administration was associated with significant increases in rCBF consistent with regional neuronal activation in both cingulate and orbitofrontal and medial prefrontal cortices, as well as caudate nuclei. These areas are responsive to nociceptive stimuli and are involved in avoidance learning, reward and addiction, visceromotor control, maintenance of attention, and pain-related affective behavior. Significant decreases were noted in both frontal and temporal areas and the cerebellum, a distribution far less extensive than that of opiate receptors in general. These data indicate that fentanyl's effects are highly localized and specifically affect cerebral regions associated with a range of pain-related behaviors. (Anesth Analg 1996;82:1247-51)