Intravenous Infusion Of Fentanyl Research Articles

A Case Study Evaluating the Efficacy of an Ad Hoc Hospital Collection Device for Fentanyl in Infant Oral Fluid.

Neonatal drug exposure is currently assessed using meconium, urine, blood, hair, or umbilical cord tissue/blood. Due to the invasiveness, challenges, and limitations of collection, and/or analytical difficulties of these matrices, oral fluid may be a more desirable matrix in diagnosing opioid exposure and risk for opioid withdrawal in neonatal abstinence syndrome. Traditional oral fluid collection devices are not viable options as they are too large for neonates' mouths and may contain chemicals on the collection pad. Unstimulated and stimulated infant oral fluid samples have been used for therapeutic drug monitoring as an alternative matrix to blood. The objective of this study was to assess the viability of a simple oral fluid collection system using a sterile foam-tipped swab rinsed in phosphate-buffered saline. Two infants were administered fentanyl for post-operative pain relief while hospitalized in the Neonatal Intensive Care Units at the Children's Hospital of Richmond of Virginia Commonwealth University. Oral fluid samples were collected at 16h, 2days, and/or 7days following the start of intravenous infusion of fentanyl. Samples were analyzed by ultra-high-pressure liquid chromatography-tandem mass spectrometry for fentanyl and norfentanyl after solid-phase extraction. In one of the three samples tested, fentanyl and norfentanyl were detected at concentrations of 28 and 78ng/mL, respectively. Based on the infusion rate, the theoretical oral fluid fentanyl concentration at steady state was calculated to be 33ng/mL.

A case of successful anesthetic management in a patient with Trousseau\u2019s syndrome who underwent surgery for malignant ovarian tumor

BackgroundTrousseau’s syndrome, also known as cancer-associated thrombosis, has several perioperative considerations, including the timing of surgery, anticoagulant therapy, and anesthetic technique. While appropriate anesthetic management is critical, few clinical reports have addressed the issue. Here, we report a patient with Trousseau’s syndrome who successfully underwent gynecological surgery 1 month after a massive cerebral infarction.Case presentationA 46-year-old woman with malignant ovarian tumor and deep venous thrombosis developed systemic thromboembolism, including a massive right cerebral infarction, despite receiving direct oral anticoagulant therapy. She was diagnosed with Trousseau’s syndrome and was transferred to our hospital 17 days after the onset of cerebral infarction with left incomplete hemiparesis. Semi-radical gynecological surgery was scheduled in another 14 days (31 days after the cerebral infarction). A temporary inferior vena cava filter was placed, and both direct oral anticoagulant and antiplatelet drugs were substituted with unfractionated heparin infusion. She underwent surgery uneventfully under general anesthesia with desflurane and remifentanil. Postoperative analgesia was achieved with a peripheral nerve block and continuous intravenous infusion of fentanyl. The tumors were fully resected, thereby only anticoagulant therapy for residual venous thrombus was continued. She had a good perioperative course and was discharged without cerebral complications or thromboembolism.ConclusionsIn patients with Trousseau’s syndrome, both early radical surgery and preventing perioperative cerebrovascular complications are critical. In our present case, Trousseau’s syndrome was successfully operated under general anesthesia 1 month after a massive cerebral infarction.

The analgesic efficacy of the continuous adductor canal block compared to continuous intravenous fentanyl infusion with a single-shot adductor canal block in total knee arthroplasty: a randomized controlled trial.

BackgroundThe adductor canal block (ACB) is an effective intervention for postoperative analgesia following total knee arthroplasty (TKA). However, the ideal ACB regimen has not yet been established. We compared the analgesic effects between a continuous ACB group and fentanyl-based intravenous patient-controlled analgesia (IV-PCA) with a single-shot ACB group.MethodsPatients who underwent TKA were randomly allocated to either a continuous ACB group (Group CACB) or IV-PCA with a single-shot ACB group (Group IVACB). Before the surgery, ultrasound guided ACB with 0.5% ropivacaine 20 cc was provided to all patients. Before skin incision, the infusion system (0.2% ropivacaine through an adductor canal catheter in group CACB vs. intravenous fentanyl in group IVACB) was connected. The postoperative pain severity; the side effects of local anesthetics and opioids; administration of rescue analgesics and anti-emetics; and sensorimotor deficits were measured.ResultsPostoperative pain severity was significantly higher in the IVACB group at 30 min, 4 h, 24 h, and 48 h after surgery. The averages and standard deviations (SD) of the NRS score of postoperative pain were 0.14 ± 0.37, 4.57 ± 2.37, 6.00 ± 1.63, and 4.28 ± 1.49, respectively in the IVACB group. Rescue analgesic requirements and quadriceps muscle strength were not statistically different between the groups throughout the postoperative period. Moreover, rescue antiemetic requirements were higher in group IVACB than group CACB.ConclusionsIn this study, the continuous ACB provided superior analgesia and fewer side effects without any significant motor deficit than the IV-PCA with a single-shot ACB.

Is the transdermal fentanyl patch an efficient way to achieve acute postoperative pain control?: A randomized controlled trial.

Backgroupd:This study investigated the plasma fentanyl concentration and efficacy of transdermal fentanyl patch (TFP) (25 μg/h) in the management of acute postoperative pain.Methods:Patients undergoing laparoscopic cholecystectomy were randomly allocated to 2 groups. The TFP group (n = 30) received a single TFP 25 μg/ h to the anterior chest wall 14 h before operation. The IV group (n = 30) received a placebo patch. After the operation, intravenous fentanyl infusion (25 μg/h) was begun with loading dose 25 μg in the IV group and only normal saline in the TFP group. Plasma fentanyl levels were measured at admission, 1, 6, 12, 24, and 48 h postoperatively. Pain severity and adverse effects were evaluated too.Results:The fentanyl level peaked 1 h after operation in the TFP group (3.27 ± 0.34 ng/mL) and 24 h postoperatively in the IV group (2.9 ± 0.42 ng/mL). Pain scores and the use of rescue analgesics were not significantly different between 2 groups. Respiratory depression was not happened in both groups.Conclusions:The TFP (25 μg/h) affixed 14 h before surgery reached a higher constant concentration than the same dose setting of a constant IV infusion of fentanyl after surgery. Although the concentration of fentanyl was higher than those of previous researches, there was no respiratory depression. But, there was no advantage of reducing pain score and the use of rescue analgesics. Clinical trial registration: (available at: http://cris.nih.go.kr, KCT0002221).

Intravenous infusion of ketamine versus fentanyl for postoperative analgesia in spine surgeries

Objective The aim of this study was to compare the intraoperative hemodynamics and postoperative recovery profile and analgesia while using ketamine versus fentanyl infusion in patients undergoing spine surgery. Background Acute pain management is an important aspect of perioperative anesthetic care. Inadequate postoperative analgesia contributes to adverse outcomes including immunosuppression, hyperglycemia, poor rehabilitation, and progression to chronic pain. Patients and methods This prospective trial included 60 adult patients with American Society of Anesthesia status I or II (undergoing elective spine surgery under general anesthesia in neurosurgery operation room of Menoufia University Hospital. They were divided into two groups of 30 patients each. In group A, analgesia is maintained intraoperative and postoperatively till 24 h with ketamine infusion (0.02–0.2 mg/kg/h). In group B, analgesia is maintained intraoperatively with fentanyl infusion (1–2 mcg/kg/h) and continued 24 h after operation. We assessed heart rate, mean arterial pressure, and duration of operation. Recovery score (Modified Aldrete Scoring System), visual analogue scale, total analgesic consumption, sedation score (Ramsey score), and occurrence of any complication in the form of nausea and vomiting, hallucination, skin rashes, or any other complications were recorded. Results There is a highly significant statistical difference between ketamine group and fentanyl group regarding hemodynamics, sedation score, visual analogue scale, first call of analgesia, and occurrence of complications. P > 0.05 was considered not statistically significant. P ≤ 0.05 was considered statistically significant. P ≤ 0.001 was considered statistically highly significant. Conclusion Low-dose ketamine infusion is more effective in postoperative pain management after spine surgery when compared with fentanyl as it maintains intraoperative hemodynamic stability and provides good postoperative analgesia. It decreases incidence of complications associated with the use of opioid infusion.

Remifentanil versus Fentanyl for pain control during elective endotracheal intubation for surfactant administration in preterm infants

Introduction: Today, the reality of pain in neonates is an undisputed fact, but pain management in clinical practice remains a challenging issue. All neonatal units should have a pain management protocol. The aim of this study was to compare the effectiveness of Remifentanil versus Fentanyl in pain control during elective endotracheal intubation for surfactant administration in preterm infants. Materials and methods: Preterm infants with gestational age between 28 weeks and 34 weeks + 6 days with Respiratory Distress Syndrome (RDS) who needed surfactant administration were divided into two groups using a random sampling method. Neonates in the first group received 2 μg/kg intravenous Fentanyl infusion and neonates in group 2 received 1 μg/kg intravenous Remifentanil before elective endotracheal intubation for surfactant therapy. The vital signs, including heart rate, oxygen saturation, mean arterial blood pressure and change in facial grimace were documented in an unnamed Premature Infant Pain Profile-Revised (PIPP-R) scoring sheet individually. Video recording was performed in both groups before, during and after the endotracheal intubation. All videos and data were interpreted and scored by two Newborn Individualized Developmental Care and Assessment Program (NIDCAP) professionals. Results: The mean PIPP-R score in the Fentanyl-treated group was 13.06 ± 3.55 and in the Remifentanil-treated group was 10.75 ± 2.93, with no statistically significant difference (p = 0.054). There was less need for Naloxone use in the Remifentanil group (p < 0.001). Incidence of apnea, severe drop in oxygen saturation, Intra-Ventricular Hemorrhage (IVH) and chest rigidity were not significantly different between the two groups. Conclusion: Although the difference was not statistically significant, Remifentanil reduced the pain score more than Fentanyl during elective endotracheal intubation in preterm infants. We recommend conducting further studies with larger study populations to determine the better drug and the optimal dosage of these drugs in neonates.

Fentanyl Induces Cerebellar Internal Granular Cell Layer Apoptosis in Healthy Newborn Pigs.

Opioids like fentanyl are regularly used in neonates for analgesia and sedation. So far, they have been reported to be safe and eligible to use. The cerebellum has become a focus of neurodevelopmental research within the last years, as it is known to play an important role in long-lasting motor, cognitive, and other behavioral changes. The cerebellar cortex is of major importance in the coordinative role of the cerebellum and highly vulnerable to injury and impaired growth. This study was performed to evaluate the apoptotic effect of intravenous fentanyl infusion on the cerebellum in healthy newborn pigs. Thirteen healthy pigs (<median 12 h old) were randomized into (1) 24 h of intravenous fentanyl at normothermia (NTFe, n = 6) or (2) non-ventilated controls at normothermia (NTCTR, n = 7). Cerebellar sections were morphologically assessed after staining with hematoxylin-eosin. In addition, paired sections were immuno-stained for cell death [Cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphate nick-end labeling (TUNEL)], and positive cells were counted in defined areas of the internal granular cell layer. In total, cells in three cerebellar gyri were counted. We found that there was an increase in cells with apoptotic morphology in the internal granular cell layer in the NTFe group. For quantification, we found a significant increase in cell death in group (1) [median (range) number of caspase-3-positive cell group (1) 8 (1-22) vs. group (2) 1 (1-6) and TUNEL-positive cells (1) 6 (1-10) vs. (2) 1 (0-4)]. In both groups, there was no difference in the number of Purkinje cells. Both groups had comparable and stable physiological parameters throughout the 24 h period. Twenty-four hours of continuous intravenous fentanyl infusion increased apoptosis in the internal granular cell layer in the cerebellum of healthy newborn pigs.

Pharmacokinetic Interaction Between Tacrolimus and Fentanyl in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND Tacrolimus and fentanyl are well-known cytochrome P450 (CYP) 3A4 substrates with a narrow therapeutic range. However, the pharmacokinetic interaction between tacrolimus and fentanyl is unclear. The aim of this study was to determine whether drug interaction exists between tacrolimus and fentanyl. MATERIAL AND METHODS A retrospective study was performed in 6 patients who had received allogeneic hematopoietic stem cell transplantation between April 2010 and March 2015. The patients received continuous intravenous infusion of fentanyl with concomitant use of tacrolimus, and the blood concentrations of tacrolimus were evaluated using fluorescence polarization immunoassay. RESULTS The clearance (CL) of tacrolimus decreased significantly from 1.28 to 0.68 mL/min/kg with concomitant use of fentanyl. The CL changed with time and dose of fentanyl administration. In addition, the CL of tacrolimus was reverted by stopping fentanyl infusion. Horn's drug interaction probability scale indicated a probable category or possible category, suggesting a drug interaction between tacrolimus and fentanyl. No patient showed a difference in hepatic or renal function before and after fentanyl administration. No additional administration of other CYP3A4 inhibitors was observed, suggesting that the drug interaction was mediated by CYP3A4. CONCLUSIONS The influence of fentanyl on the pharmacokinetics of tacrolimus was demonstrated to be of clinical importance. It is proposed that the dose of tacrolimus be reduced by 40% when used in combination with fentanyl.

Conversion from prolonged intravenous fentanyl infusion to enteral methadone in critically ill children.

AIMTo describe our institutional experience with conversion from intravenous (IV) fentanyl infusion directly to enteral methadone and occurrence of withdrawal in critically ill mechanically ventilated children exposed to prolonged sedation and analgesia.METHODSWith Institutional Review Board approval, we retrospectively studied consecutively admitted invasively mechanically ventilated children (0-18 years) sedated with IV fentanyl infusion > 5 d and subsequently converted directly to enteral methadone. Data were obtained on subject demographics, illness severity, daily IV fentanyl and enteral methadone dosing, time to complete conversion, withdrawal scores (WAT-1), pain scores, and need for rescue opioids. Patients were classified as rapid conversion group (RCG) if completely converted ≤ 48 h and slow conversion group (SCG) if completely converted in > 48 h. Primary outcome was difference in WAT-1 scores at 7 d. Secondary outcomes included differences in overall pain scores, and differences in daily rescue opioids.RESULTSCompared to SCG (n = 21), RCG (n = 21) had lower median WAT-1 scores at 7 d (2.5 vs 5, P = 0.027). Additionally, RCG had lower overall median pain scores (3 vs 6, P = 0.007), and required less median daily rescue opioids (3 vs 12, P = 0.003) than SCG. The starting daily median methadone dose was 2.3 times the daily median fentanyl dose in the RCG, compared to 1.1 times in the SCG (P = 0.049).CONCLUSIONWe observed wide variation in conversion from IV fentanyl infusion directly to enteral methadone and variability in withdrawal in critically ill mechanically ventilated children exposed to prolonged sedation. In those children who converted successfully from IV fentanyl infusion to enteral methadone within a period of 48 h, a methadone:fentanyl dose conversion ratio of approximately 2.5:1 was associated with less withdrawal and reduced need for rescue opioids.

Clinical usefulness of intravenous constant rate infusion of fentanyl and medetomidine under sevoflurane anesthesia in Thoroughbred racehorses undergoing internal fixation surgery

ABSTRACTA total of 20 racehorses with longitudinal fractures underwent internal fixation surgery under sevoflurane anesthesia combined with infusion of medetomidine (3 µg/kg/hr) alone (10 horses, group M) or medetomidine and fentanyl (7 µg/kg/hr) (10 horses, group FM). In group FM, the end-tidal sevoflurane concentration during surgery was maintained significantly lower than in group M (2.8–2.9% for group M vs. 2.2–2.6% for group FM, P<0.01). The mean arterial blood pressure was maintained over 70 mmHg using dobutamine infusion (group M, 0.36–0.54 µg/kg/min; group FM, 0.27–0.65 µg/kg/min), and the recovery qualities were clinically acceptable in both groups. In conclusion, co-administration of fentanyl and medetomidine by constant rate infusion may be a clinically useful intraoperative anesthetic adjunct for horses to reduce the requirement of sevoflurane when they undergo orthopedic surgery.

Post-operative myocardial infarction complicating donor hepatectomy: Implications for donor safety.

Sir, A 56-year-old post-menopausal lady was evaluated as a liver donor for her daughter who had fulminant liver failure. Her medical history was unremarkable, and post-menopausal state and age above 50 years were the only associated risks. A 12-lead electrocardiogram and two-dimensional echocardiography were both normal. We identified her as intermediate surgical risk[1] with clinical cardiopulmonary reserve of six metabolic equivalents. Standard protocols for anaesthesia for hepatectomy were performed; however, an epidural catheter was abandoned in view of technical difficulty and analgesia was provided with an intravenous fentanyl infusion. The procedure lasted for 6.5 h with blood loss of 600 ml and the patient was extubated at the end of procedure. Continuous analgesia was provided with an intravenous infusion of fentanyl targeting a pain score <4 on the visual analogue scale. On the 1st post-operative day (POD), the patient was pain-free, ambulant and haemodynamically stable. Her heart rate averaged 65/min, central venous pressure 7–8 mmHg, haemoglobin 10.8 g/dL, serum aspartate aminotransferase 684 IU/L, serum alanine aminotransferase 565 IU/L and international normalised ratio (INR) 1.46. On the second POD, the patient developed sudden hypotension with cardiac arrest. There was no evidence of hypovolaemia or bleeding at the surgical site. Standard cardiopulmonary resuscitation was initiated with successful return of spontaneous circulation after two cycles. The blood pressure was then maintained with infusions of adrenaline and dopamine. A 12-lead electrocardiogram suggested an inferolateral wall ST-elevation myocardial infarction [STEMI, Figure 1]. A coronary angiogram showed 80% stenosis of the distal right coronary artery with normal flow in all other vessels. Percutaneous coronary intervention was performed with a bare metal stent that was exchanged for a covered stent following perforation at the site of stenting. A pigtail catheter was inserted into the pericardial sac [Figure 2]. Infusion of eptifibatide and intravenous heparin were administered at the time of intervention. The patient bled 1.8 L from the abdominal drain and 330 ml from the pericardial sac, for which she was transfused two units of packed red blood cells and two units of fresh frozen plasma (INR was 4.23). She was weaned off the ventilator on the 4th day following intervention and was discharged on the 16th POD. Figure 1 Electrocardiogram showing inferolateral wall ST-elevation myocardial infarction Figure 2 Pigtail catheter in the pericardial sac Despite guidelines for donor selection,[2] emotional factors and donor availability confound the selection in life-threatening situations. Donor deaths range from 0.5% to 2% in right hepatectomy, and myocardial infarction has also been one of the causes.[3] As history suggested a good cardiopulmonary reserve with a revised cardiac risk index[1] score of 0.9%, we did not consider the need for stress testing. An exercise stress testing, dobutamine echocardiogram or assessment of anaerobic threshold may have been predictive of major adverse cardiac events (MACE) in this patient.[1] In contrast to the American College of Cardiology guidelines,[1] the European Society of Cardiology[4] guidelines classify liver resection surgery as high surgical risk for MACE. It is possible that stress of surgery pre-disposed the STEMI following plaque rupture.[4] Percutaneous intervention was the treatment of choice as surgical revascularisation or thrombolysis is associated with increased bleeding post-operatively.[1] Although coagulation disturbances are known after major hepatectomy, epidural analgesia is considered acceptable if performed judiciously.[5] Living donation is a viable option for fulminant liver failure, and marginal donors are accepted in the background of restricted donor availability as a life-saving measure. As the donor undergoes surgery that is not indicated for his well-being, rigorous adherence to standard protocols in donor evaluation[6] even in emergent situations and communication of potential life-threatening complications is necessary for living donor transplants. In the light of our report, exercise stress testing or pharmacological stress testing for prediction of MACE should be considered in high surgical risk procedures including donor hepatectomy. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Response to intravenous fentanyl infusion predicts subsequent response to transdermal fentanyl.

Prediction of the response to transdermal fentanyl (FENtd) before its use for chronic pain is desirable. We tested the hypothesis that the response to intravenous fentanyl infusion (FENiv) can predict the response to FENtd, including the analgesic and adverse effects. The study subjects were 70 consecutive patients with chronic pain. The response to fentanyl at 0.1 mg diluted in 50 ml of physiological saline and infused over 30 min was tested. This was followed by treatment with FENtd (Durotep MT patch 2.1 mg) at a dose of 12.5 µg/h for 2 weeks. Pain intensity before and after FENiv and 2 weeks after FENtd, and the response to treatment, were assessed by the numerical rating scale (NRS), clinical global impression-improvement scale (CGI-I), satisfaction scale (SS), and adverse effects. The NRS score decreased significantly from 7 (4-9) [median (range)] at baseline to 3 (0-8) after FENiv (p < 0.001), and to 4 (1-8) after FENtd (p < 0.001). The effects of FENiv, as evaluated by ΔNRS, CGI-I, and SS, were significantly greater than those of FENtd (p < 0.001, each), but not by the frequency and the severity of adverse effects, with the exception of dizziness. ΔNRS, and severity of adverse effects (drowsiness, dizziness, nausea, dry mouth, and pruritus) of FENiv correlated significantly with those of FENtd (rs > 0.04, each). The analgesic and side effects after intravenous fentanyl infusion can be used to predict the response to short-term transdermal treatment with fentanyl.

The relationship of cerebral oximeter and postoperative cognition function of geriatric patients under intravenous anesthesia using creatine phosphate disodium salt

Objective To discuss the relationship of perioperative regional cerebral saturation of oxygenation (rSO2) and postoperative cognition function alteration of geriatric patients under intravenous anesthesia using creatine phosphate disodium salt,and to establish the clinical practical guides.Methods Sixty ASA Ⅰ-Ⅱ patients,aged＞60 y scheduled for selective abdominal surgeries or surgeries on lower limb were enrolled in this study.We used a completely randomized grouping design for this study and the 20 patients were divided into 3 groups:creatine phosphate disodium salt group 1 (C1),creatine phosphate disodium salt group 2 (C2),Control group (C).All patients were not premeditated with atropine 0.5 mg until entering the operation room.Anesthesia was induced with intravenous infusion of propofol,fentanyl and cisatracurium slowly,The anesthesia was maintained by intravenous propofol infusion in target controlled infusion target controlled infusion (TCI) (3 μg) and remifentanyl (0.2 μg·kg-1·min-1-0.4 μg·kg-1·min-1) infusion,intravenous bolus cisatracurium (0.07 mg/kg-0.10 mg/kg).After tracheal intubation,all patients were mechanically ventilated with expiration carbon dioxide pressure (PERCO2) at normal scale.The rSO2 was continuously monitored and recorded in operations.The mini-mental state examination (MMSE),trail-making test and grooved pegboard test were adopted to access cognitive function 24 h before surgery and 4,8,12,24 h after surgery.Results ① There were no significantly difference of general status among the three groups(P＞0.05).② The scales of MMSE,trail-making test and grooved pegboard test were not different 24 h before operations among three groups (P＞0.05).Compared with scales of MMSE before operation,4,8,12 h after operation in all patients were significantly lower (P＜0.05).Three groups of patients trail-making test and the grooved pegboard test time comparison experiment found:there were no difference between preoperative and postoperative testing time (P＞0.05),which time of patients in group C2 completed the task significantly shorter than group C1,the control group of patients needed more time to complete the task.Comparison of postoperative cognitive function changes after 4 h,cognitive function changes occurred in the control group of patients with 3 patients (15％),creatine phosphate (C2) of patients in group 1 patient (5％),creatine phosphate sodium (C1) patients,2 patients (10％).After 8 h,patients in the control group 2 patients (10％),creatine phosphate (C1) patients in group 1 patients (5％),phosphoric acid muscle sodium (C2) cognitive function in patients recovered.Postoperative 12 h,patients in the control group only one case (5％),creatine phosphate groups (group C1 and C2) cognitive function in patients recovered,after 24 h,cognitive function of all patients recovered,the delirium did not occur in all patients entered the study.(③ The scales of cognitive tests were higher in group C2 and group C1 than C (P＜0.01).The numbers of rSO2 in the three groups were identical (P＞0.05).Conclusions Creatine phosphate disodium salt can reduce the occurrence of postoperative cognitive dysfunction in geriatric patients combined the intravenous and inhalational anesthesia.The results may relate to its neural protection effects,unique natural energy supply and increasing central neural system tolerance of ischemia and hypoxia. Key words: Geriatric patients; Postoperative cognition function; Regional cerebral saturation of oxygenation; Creatine phosphate disodium salt

Impact of CYP3A5*3 on Plasma Exposure and Urinary Excretion of Fentanyl and Norfentanyl in the Early Postsurgical Period

The pharmacokinetic characteristics of intravenous fentanyl have not been fully clarified in the early postsurgical period. The aim of this study was to evaluate the plasma exposure and urinary excretion of fentanyl and norfentanyl according to cytochrome P450 (CYP) 3A5 genetic polymorphism. Fifty-two adult Japanese postoperative patients receiving a continuous intravenous fentanyl infusion were enrolled. Plasma concentrations of fentanyl and norfentanyl were determined at 24 hours after the operation, and their urinary excretion from 12 to 36 hours was evaluated. Plasma concentrations of fentanyl normalized for infusion rate were significantly higher in the *3/*3 group than in the *1 carrier group. The plasma concentration ratio of norfentanyl to fentanyl was significantly lower in the *3/*3 group than in the *1 carrier group. Urinary excretion rates of fentanyl and norfentanyl were 4.4% and 71%, respectively, and no significant differences were observed between the CYP3A5 genotypes. Renal clearance ratios of fentanyl and norfentanyl to creatinine were 0.34 and 3.4, respectively. There were no significant differences in the renal clearance ratios between the genotypes. Free fractions of fentanyl and norfentanyl in human plasma were 4.9% and 95%, respectively. Total and nonrenal clearance of fentanyl were significantly lower in the *3/*3 group than in the *1 carrier group. CYP3A5*3 affected the plasma exposure of fentanyl but not urinary excretion in our postoperative patients. The renal clearance ratios of fentanyl and norfentanyl to creatinine were much higher than their free fractions in plasma. These findings suggest a slight contribution of renal tubular secretion of fentanyl and norfentanyl to their plasma exposures.

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Introduction: Hyperosmotic agents are the mainstay of therapy for intra-cranial hypertension. However, little is known about the cerebral metabolic response to different hyper-osmotic agents. Methods: Pigs (35–45 Kg), anesthetized using a continuous intravenous infusion of midazolam, fentanyl and rocuronium, were managed to achieve normal cardiac output and mean arterial pressure and ventilated to maintain normoxia, normocapnia and normal cerebral perfusion. A balloon catheter was used to increase intracranial pressure (ICP). When ICP reached 30 mmHg, animals were randomized to receive one iso-osmolar load of 255 mOsm/dose of either 20% mannitol (M20%) or 7.45% hypertonic saline (HS 7.45%) as a 30 min bolus through a central vein. The effectiveness of the solution to decrease ICP was arbitrarily defined as an ICP decrease of ≥3 mmHg after the infusion. Measurements of cerebral perfusion (intra-parenchymal pressure, cerebral perfusion pressure, brain oxygen tension, PtO2), systemic perfusion (mean arterial pressure [MAP], cardiac output (CO), serum lactate) and neuronal response (lactate/pyruvate ratio, L/P) were taken at baseline (twice), at ICPs of 15 and 30 mmHg and at T30, T60, T120 and T180 min after the end of the infusion. After 5 hours, the animal was sacrificed. A linear mixed model was used to analyze the time courses of considered variables. Results: All values are express as mean (SD). HS 7.45% administration resulted in lower ICP at T180 min: 27.1 mmHg (11.64) vs. 36.1 mmHg (11.9); mean difference: 9 mmHg ±4.2;p=0.04) and higher PtO2 at T180: 41.0 (14.9) vs. 21.7 (13.1); mean difference: 19.2 mmHg ±7.1 mmHg, p=0.01. We found no significant difference in the L/P ratio at T180 min: 67.5 (31.8) vs. 65.4 (115.41); mean difference: 2.1 ± 34.2, p=0.95, or on MAP, CO or lactate levels between the two groups. Conclusions: In this model, administration of HS 7.45% was more effective than M20% in reducing ICP and increasing PtbO2. These differences were not associated with significant differences in systemic variables or regional metabolism.

Efficacy of continuous wound infiltration of local anesthetic for pain relief after gynecologic laparoscopy

ObjectiveTo assess the efficacy of analgesia provided by continuous ropivacaine wound infiltration after gynecologic laparoscopy. MethodsSixty patients who underwent gynecologic laparoscopy at Ajou University School of Medicine, Suwon, Republic of Korea, between March and May 2012 were randomized to receive either intravenous fentanyl and ketorolac infusion on demand by patient-controlled analgesia (IV PCA group, n=31) or continuous wound infiltration of local ropivacaine (CWI group, n=29). Postoperative pain and postoperative nausea and vomiting (PONV) were assessed via a visual analog scale. The number of patients who requested rescue analgesia was recorded. ResultsThere was no significant difference in postoperative pain between the 2 groups, but more patients requested rescue analgesia in the CWI group than in the IV PCA group in 24hours (18 versus 9 patients, respectively; P=0.010). The PONV scores at 12 and 24hours were, respectively, 0.28 and 0.27 in the CWI group, and 0.71 and 0.73 in the IV PCA group (P=0.004). Nine patients requested cessation of IV PCA because of severe nausea or vomiting. ConclusionContinuous ropivacaine wound infiltration was found to be as effective as patient-controlled analgesia for postoperative pain relief after gynecologic laparoscopy. This technique provides good analgesia with less opioid analgesic requirement and few adverse effects.

Evaluation of the isoflurane‐sparing effects of fentanyl, lidocaine, ketamine, dexmedetomidine, or the combination lidocaine‐ketamine‐dexmedetomidine during ovariohysterectomy in dogs

ObjectiveTo evaluate the isoflurane‐sparing effects of an intravenous (IV) constant rate infusion (CRI) of fentanyl, lidocaine, ketamine, dexmedetomidine, or lidocaine‐ketamine‐dexmedetomidine (LKD) in dogs undergoing ovariohysterectomy. Study designRandomized, prospective, blinded, clinical study. AnimalsFifty four dogs. MethodsAnesthesia was induced with propofol and maintained with isoflurane with one of the following IV treatments: butorphanol/saline (butorphanol 0.4 mg kg−1, saline 0.9% CRI, CONTROL/BUT); fentanyl (5 μg kg−1, 10 μg kg−1 hour−1, FENT); ketamine (1 mg kg−1, 40 μg kg−1 minute−1, KET), lidocaine (2 mg kg−1, 100 μg kg−1 minute−1, LIDO); dexmedetomidine (1 μg kg−1, 3 μg kg−1 hour−1, DEX); or a LKD combination. Positive pressure ventilation maintained eucapnia. An anesthetist unaware of treatment and end‐tidal isoflurane concentration (Fe′Iso) adjusted vaporizer settings to maintain surgical anesthetic depth. Cardiopulmonary variables and Fe′Iso concentrations were monitored. Data were analyzed using anova (p < 0.05). ResultsAt most time points, heart rate (HR) was lower in FENT than in other groups, except for DEX and LKD. Mean arterial blood pressure (MAP) was lower in FENT and CONTROL/BUT than in DEX. Overall mean ± SD Fe′Iso and % reduced isoflurane requirements were 1.01 ± 0.31/41.6% (range, 0.75 ± 0.31/56.6% to 1.12 ± 0.80/35.3%, FENT), 1.37 ± 0.19/20.8% (1.23 ± 0.14/28.9% to 1.51 ± 0.22/12.7%, KET), 1.34 ± 0.19/22.5% (1.24 ± 0.19/28.3% to 1.44 ± 0.21/16.8%, LIDO), 1.30 ± 0.28/24.8% (1.16 ± 0.18/32.9% to 1.43 ± 0.32/17.3%, DEX), 0.95 ± 0.19/54.9% (0.7 ± 0.16/59.5% to 1.12 ± 0.16/35.3%, LKD) and 1.73 ± 0.18/0.0% (1.64 ± 0.21 to 1.82 ± 0.14, CONTROL/BUT) during surgery. FENT and LKD significantly reduced Fe′Iso. Conclusions and clinical relevanceAt the doses administered, FENT and LKD had greater isoflurane‐sparing effect than LIDO, KET or CONTROL/BUT, but not at all times. Low HR during FENT may limit improvement in MAP expected with reduced Fe′Iso.

Propofol and Fentanyl Take Longer for Induction of Anesthesia in Aortic Regurgitation: A Case-Controlled Prospective Study

This study was conducted to determine if induction time of anesthesia in patients with aortic regurgitation (AR) is different from patients with a normal aortic valve (AV). A prospective, case-control study. A single institutional study conducted in a tertiary care teaching hospital. Twenty-four male patients scheduled for cardiac surgery, group I (n = 12) patients with competent AV and group 2 (n = 12) with severe AR. General anesthesia was induced by intravenous infusion of propofol and fentanyl. Continuous measurements of heart rate, intra-arterial blood pressure, and bispectral index were recorded. Induction doses of propofol and fentanyl were analyzed and compared. There was significant difference between the 2 groups in terms of induction time of anesthesia (mean ± SD 308 ± 68.2 seconds in group 1 v 445 ± 97.9 seconds in group 2). The patients in group 2 (AR) required significantly larger doses of propofol (0.91 ± 0.40 mg/kg) than the patients in group 1 (0.49 ± 0.17 mg/kg). Similarly, fentanyl dose was increased in the group 2 patients (20.8 ± 15.9 µg/kg) compared with the group 1 patients (9.2 ± 2.9 µg/kg). The authors concluded that there was a significant prolongation of the induction time of anesthesia and the need of larger doses of propofol and fentanyl by slow intravenous infusion regimen in patients with AR compared with patients with a competent aortic valve.

Comparison of the postoperative analgesia of intravenous infusion of adenosine and fentanyl

Comparison of the postoperative analgesia of intravenous infusion of adenosine and fentanyl

Cardiopulmonary effects of intravenous fentanyl infusion in dogs during isoflurane anesthesia and with concurrent acepromazine or dexmedetomidine administration during anesthetic recovery

To evaluate the cardiopulmonary effects of IV fentanyl administration in dogs during isoflurane anesthesia and during anesthetic recovery with or without dexmedetomidine or acepromazine. 7 sexually intact male purpose-bred hound-type dogs aged 11 to 12 months. Dogs received a loading dose of fentanyl (5 μg/kg, IV) followed by an IV infusion (5 μg/kg/h) for 120 minutes while anesthetized with isoflurane and for an additional 60 minutes after anesthesia was discontinued. Dogs were randomly assigned in a crossover design to receive dexmedetomidine (2.5 μg/kg), acepromazine (0.05 mg/kg), or saline (0.9% NaCl) solution (1 mL) IV after anesthesia ceased. Cardiopulmonary data were obtained during anesthesia and for 90 minutes after treatment administration during anesthetic recovery. Concurrent administration of fentanyl and isoflurane resulted in significant decreases in mean arterial blood pressure, heart rate, and cardiac index and a significant increase in Paco2. All but Paco2 returned to pretreatment values before isoflurane anesthesia was discontinued. During recovery, dexmedetomidine administration resulted in significant decreases in heart rate, cardiac index, and mixed venous oxygen tension and a significant increase in arterial blood pressure, compared with values for saline solution and acepromazine treatments. Acepromazine administration resulted in significantly lower blood pressure and higher cardiac index and Po2 in mixed venous blood than did the other treatments. Dexmedetomidine treatment resulted in significantly lower values for Pao2 and arterial pH and higher Paco2 values than both other treatments. Fentanyl resulted in transient pronounced cardiorespiratory effects when administered during isoflurane anesthesia. During anesthetic recovery, when administered concurrently with an IV fentanyl infusion, dexmedetomidine resulted in evidence of cardiopulmonary compromise and acepromazine transiently improved cardiopulmonary performance.