Continuous Intravenous Infusion Of Fentanyl Research Articles

Case report of pharmacokinetic analysis of continuous intravenous infusion of fentanyl in a patient with severe burn: burn shock stage complicates pain management

BackgroundFentanyl is widely used as an analgesic and sedative for patients with severe burn injuries in intensive care units. However, pharmacokinetic (PK) data for fentanyl, particularly for continuous intravenous infusion during the acute phase of burn injuries, are limited. Here, we report the clinical course and changes in blood fentanyl concentrations during the acute phase in a patient with severe burns treated with continuous intravenous infusion of fentanyl.Case presentationA woman in her 40s, with burns caused by a gas cylinder explosion, was transported to our hospital. The patient had burn wounds on face, neck, shoulders, and all four extremities, with a total burn area of 39.0%. For pain relief, the patient received a continuous infusion of 0.01 mg/mL fentanyl (20–30 µg/h) with a target blood concentration of 1.0–1.5 ng/mL, but continued to suffer from pain due to burning during the acute phase. We measured the blood fentanyl concentrations and found that all concentrations obtained during the acute phase were subtherapeutic. Notably, during the burn shock stage, blood concentrations of fentanyl were 0.50 ng/mL on day 1 and 0.66 ng/mL on day 2, indicating that the blood concentration did not rise sufficiently for the dosage. From days 0 to 2, the patient was administered a massive fluid load for burn shock. After the burn shock stage resolved, fentanyl concentrations gradually approached the target range, and the pain rating scale improved, even though the fentanyl administration rate remained unchanged (30 µg/h).ConclusionsMajor changes in the fluid volumes of body compartments that occur with large burns might increase the volume of fentanyl distribution, thereby lowering its concentration when a standard dose is administered. Our findings indicate that the PK of fentanyl in patients with severe burns can be substantially affected, especially during the shock phase, implying the importance of titrating analgesics for clinical efficacy in the acute phase.

Use of Methadone Versus Oxycodone to Facilitate Weaning of Parenteral Opioids in Critically Ill Adult Patients.

No previous literature has compared methadone with oxycodone for intravenous (IV) opioid weaning. To determine if a weaning strategy using enteral methadone or oxycodone results in faster time to IV opioid discontinuation. This was a single-center, retrospective, cohort medical record review of mechanically ventilated adults in an intensive care unit (ICU) who received a continuous IV infusion of fentanyl or hydromorphone for ≥72 hours and an enteral weaning strategy using either methadone or oxycodone from January 1, 2020, through December 31, 2021. Differences between groups were controlled for using Cox proportional hazards models. The primary outcome was time to continuous IV opioid discontinuation from the initiation of enteral opioids. Secondary outcomes included the primary endpoint stratified for COVID-19, duration of mechanical ventilation, ICU and hospital length of stay, and safety measures. Ninety-three patients were included, with 36 (38.7%) patients receiving methadone and 57 (61.3%) receiving oxycodone. Patients weaned using methadone received IV opioids significantly longer before the start of weaning (P = 0.04). However, those on methadone had a significantly faster time to discontinuation of IV opioids than those on oxycodone, mean (standard deviation) 104.7 (79.4) versus 158.3 hours (171.2), P = 0.04, and, at any time, were 1.89 times as likely to be weaned from IV opioids (hazard ratio, HR 1.89, 95% confidence interval, CI 1.16-3.07, P = 0.01). This was the first study showing enteral methadone was associated with a shorter duration of IV opioids without differences in secondary outcomes compared with oxycodone. Prospective research is necessary to confirm this finding.

Impact of Opioid Administration in the Intensive Care Unit and Subsequent Use in Opioid-Naïve Patients.

Opioids are a mainstay of therapy for patients in the intensive care unit (ICU) as part of the analgesia-first approach to sedation. Despite knowledge of acute consequences of opioid based analgosedation, less is known about the potential long-term consequences, including the effect of opioid administration in the ICU on subsequent opioid use in opioid-naïve patients. To evaluate the relationship between ICU opioid administration to opioid-naïve patients and subsequent opioid use following discharge. A query of the electronic medical record was performed to identify opioid-naïve adult patients admitted directly to an ICU. Patients who received continuous intravenous infusion of fentanyl, hydromorphone, or morphine were screened for inclusion into the analysis. Of the 342 patients included for analysis, 164 (47.1%) received an opioid at hospital discharge. In total, 17 of the 342 patients (5.0%) became long-term users, noted to be more common in patients who received an opioid prescription at discharge (8.7% vs 1.6%; P = 0.006). Neither total ICU morphine milligram equivalent (MME) nor average daily ICU MME administration were found to correlate with daily MME prescription quantity at discharge (R2 = 0.008 and R2 = 0.03, respectively). Following control for potentially confounding variables, total ICU MME administration remained an insignificant predictor of subsequent receipt of an opioid prescription at discharge and long-term opioid use. This study failed to find a significant relationship between ICU opioid use in opioid-naïve patients and subsequent opioid use. These findings highlight the need to focus on transitions points between the ICU and discharge as potential opportunities to reduce inappropriate opioid continuation.

The Comparison of Postoperative Pain Between Umbilical and Suprapubic Incision in Laparoscopic Liver Resection

Introduction: In laparoscopic hepatectomy, wounds for specimen removal are indispensable. The umbilical incision is commonly used in laparoscopic colectomy and is familiar to gastroenterologists. On the other hand, it has been pointed out that the suprapubic incision method, which is often performed in the gynecological surgery, is superior in terms of postoperative pain, but there is no report comparing the two. Method: From November 2007 to May 2019, 19 patients who underwent laparoscopic lateral segmental resection at our hospital under complete arthroscopy were included. In 11 patients with umbilical incision and 8 patients with suprapubic incision, the operation time, bleeding volume, wound length, duration of continuous intravenous fentanyl infusion immediately after surgery and the number of flushes, and period of regular oral administration of NSAIDs were evaluated. Results: There was no significant difference between the two groups in terms of patient background, age, operation time, and bleeding volume. However, suprapubic incision was significantly longer in wound length than in umbilical incision. Subsequently, for postoperative pain, the duration of continuous intravenous fentanyl administration was 1 day (1-2 days) for umbilical incisions and 1.5 days (1-2 days) for suprapubic incisions, with no significant difference. About the number of fentanyl, the result was comparable. In the period of regular NSAIDs administration, there was also no significant difference with POD14 (POD5-35) in umbilical incisions and POD8 (POD7-32) in suprapubic incisions. Conclusions: In laparoscopic hepatectomy, extirpation of the specimen by umbilical incision is acceptable.

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.

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.

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.

Postoperative continuous intravenous infusion of fentanyl is associated with the development of orthostatic intolerance and delayed ambulation in patients after gynecologic laparoscopic surgery

Early ambulation is essential for rapid functional recovery after surgery; however, orthostatic intolerance may delay recovery and cause syncope, leading to potential serious complications such as falls. Opioids may contribute to orthostatic intolerance because of reduced arterial pressure and associated reduction in cerebral blood flow and oxygenation. This study aimed to examine the effect of postoperative continuous infusion of fentanyl on orthostatic intolerance and delayed ambulation in patients after gynecologic laparoscopic surgery. In this retrospective cohort study, data from 195 consecutive patients who underwent gynecologic laparoscopic surgery were analyzed to evaluate the association between postoperative continuous infusion of fentanyl and the incidence of orthostatic intolerance or delayed ambulation. The primary outcome was defined as delayed ambulation, an inability to ambulate on postoperative day 1. The secondary outcome was defined as orthostatic intolerance and symptoms associated with ambulatory challenge, including dizziness, nausea and vomiting, feeling hot, blurred vision, and eventual syncope. Multivariate logistic regression was used to determine the independent predictors of delayed ambulation and orthostatic intolerance. There were 24 cases with documented orthostatic intolerance and 5 with delayed ambulation. After multivariate logistic regression modeling, postoperative continuous infusion of fentanyl was found to be significantly associated with both orthostatic intolerance [adjusted odds ratio (95% confidence interval), 34.78 (11.12-131.72)] and delayed ambulation [adjusted odds ratio (95% confidence interval), 8.37 (1.23-72.15)]. Postoperative continuous infusion of fentanyl is associated with increased orthostatic intolerance and delayed ambulation in patients after gynecologic laparoscopic surgery.

フェンタニル注射剤持続静脈内投与と貼付剤(リザーバー型)の投与量換算比に関する研究

フェンタニル注射剤持続静脈内投与と貼付剤(リザーバー型)の投与量換算比に関する研究

Continuous intravenous infusion of fentanyl suggests improved safety over morphine in preterm infants undergoing laser therapy in retinopathy of prematurity

Introduction: Currently, there is no consensus regarding the optimal mode of anesthesia for retinopathy of prematurity (ROP) laser treatment. Studies have established that general anesthesia with intubation confers significant risk in preterm neonates, and that opioid analgesia with benzodiazepine sedation is ideal when the NICU is equipped for such surgical procedures. While small retrospective studies have looked at the safety and efficacy of morphine (n = 130), ketamine (n = 11), and remifentanil (n = 6), no studies have looked at fentanyl for ROP laser surgery.

Dosing Evaluation of Continuous Intravenous Fentanyl Infusions in Overweight Children: A Pilot Study

The purpose of this study was to assess the appropriateness of weight-based dosing of continuous intravenous infusion of fentanyl in overweight/obese versus normal-weight children admitted to the pediatric intensive care unit (PICU). This retrospective, pilot study included 5- to 12-year-old children admitted to the PICU over a 2-year period who received continuous intravenous infusion fentanyl for ≥ 4 days. The overweight/obese group included children with a body mass index (BMI) ≥ 85th percentile, while the control group included children with BMI < 85th percentile. The primary objective was to compare the number of fentanyl continuous intravenous infusion dosage changes required per day to achieve adequate sedation between groups. Secondarily, opioid withdrawal symptoms following the discontinuation of fentanyl and concomitant sedative/analgesic regimens were analyzed between groups. Student t tests and chi-square analyses were performed as appropriate, with an a priori alpha of p≤0.05. Sixteen normal-weight and 15 overweight/obese patients with 18 and 16 individual infusions were identified, respectively. No statistical difference was found between groups for the number of dosage changes per day, 0.92 versus 0.69 (p=0.16). Five patients in each group experienced withdrawal (p=0.71). The total number of concomitant bolus doses received was greater in the overweight/obese group but did not reach statistical significance. There was a numerical, but statistically nonsignificant difference in the number of sedative/analgesic bolus doses and dosing changes per day between groups. Larger studies are warranted to determine the optimal dosing strategy for continuous intravenous infusion fentanyl in overweight/obese children.

Continuous intravenous infusion of fentanyl for pain due to stomatitis, pharyngitis, and esophagitis after hematopoietic stem cell transplantation

【目的】造血幹細胞移植(以下, HSCT)後の口内炎・咽頭食道炎による疼痛に対するフェンタニル持続静注の有用性を検討した. 【方法】粘膜障害による疼痛が出現したHSCT患者15例を対象に, フェンタニル持続静注を12.5 μg/時より開始, 適宜増減して疼痛コントロールを行った. フェンタニル開始時と最大投与時の口腔粘膜障害grade, 疼痛スケール, 含嗽回数や歯磨き回数などのQOL指標を比較した. 【結果】フェンタニル開始の移植後病日は中央値で第7病日, 投与期間中央値は12日間だった. 最大投与量中央値は980 (243.8～3,010)μg/日でフェンタニル開始後中央値は5日目だった. 口腔粘膜障害gradeは投与開始時に比べ最大投与時は有意に上昇していたが, 疼痛スケールはむしろ有意に軽減しており, QOL指標は有意差なく維持されていた. 【結語】フェンタニル持続静注は, 粘膜障害悪化時も疼痛増強を抑えてQOLを保ち, セルフケア維持に寄与した可能性がある. Palliat Care Res 2011; 6(2): 246-252

Fat Graft before Breast Reconstruction by Latissimus Dorsi

Sir: Delayed breast reconstruction by means of latissimus dorsi musculocutaneous flap and implant is a common procedure after mastectomy and radiotherapy, especially in patients at high risk for complications, because of the reliable vascularity associated with this flap.1 However, in such patients, we have observed necrosis of the irradiated skin around the flap (Fig. 1).Fig. 1.: Necrosis of the soft tissues beneath the latissimus dorsi flap 1 month after breast reconstruction: the underlying implant is exposed. Note that the flap survived.Fat grafting is a routine procedure for refinements after breast reconstruction and has been shown to be a powerful regenerative treatment for irradiated2 and injured tissues, improving skin quality, vascularity, scar retraction,3 ulcers,4 and pain.5 For these reasons, we decided to perform fat grafting at the mastectomy irradiated area before breast reconstruction by latissimus dorsi musculocutaneous flap. From March of 2007 to January of 2009, we enrolled five patients who were candidates for delayed breast reconstruction by means of latissimus dorsi musculocutaneous flap surgery. The patients had a mean age of 49.2 years (range, 39 to 67 years). All of them were smokers and one was obese and diabetic. They had undergone mastectomy, chemotherapy, and radiotherapy 3 to 10 months previously and presented poor thickness, vascularization, and tissue quality of the recipient site. All patients underwent only one fat graft under continuous intravenous fentanyl infusion associated with local anesthesia. After tumescent infiltration, liposuction of the subumbilical area was performed. An adipose tissue sample of approximately 100 ml was obtained and processed following Coleman's technique. A volume of 46 to 60 ml (average, 54.8 ml) was injected using an 18-gauge angiographic needle with a snap-on wing at the dermal-subdermal junction of the irradiated, retracted mastectomy area. No complications occurred. Three months after fat grafting, we performed breast reconstruction by means of latissimus dorsi musculocutaneous flap and implant placement. We verified that skin texture, softness, and elasticity of the irradiated mastectomy area had improved dramatically after fat grafting. The skin paddle was oriented horizontally. Suction drains were placed at the donor and recipient sites and removed 3 to 5 days later. All patients were followed up at 2 weeks, 1 month, 3 months, and 6 months after surgery. No necrosis or dehiscence occurred. The final outcome was good and all patients were satisfied (Fig. 2).Fig. 2.: Postoperative view 1 month after breast reconstruction by latissimus dorsi flap and implant. Fat grafting had been performed 3 months before.Our preliminary experience shows that fat grafting is an additional tool with which to prevent surrounding skin necrosis when it is expected because of high-risk local factors and systemic conditions. We compared these data with the results of six breast reconstructions using the latissimus dorsi musculocutaneous flap performed from 2004 to 2006 without previous fat grafting: this complication had occurred in three patients, all of whom were smokers and had undergone radiotherapy and chemotherapy. Adipose tissue is easily harvested, with low morbidity. The regenerative properties of fat graft, vascular improvement, and architectural remodeling of soft tissues could play a role in preparing an irradiated site for major surgery. Not only mesenchymal stem cells from the stromal fraction of harvested fat2 but also molecular components and the surrounding microenvironment are presumed to be involved. DISCLOSURE The authors have no financial interests or commercial associations to disclose. There was no funding support for this study. Federico Villani, M.D. Fabio Caviggioli, M.D. Francesco Klinger, M.D. Luca Maione, M.D. Marco Klinger, M.D. Cattedra di Chirurgia Plastica Università degli Studi di Milano U.O. Chirurgia Plastica 2 IRCCS Istituto Clinico Humanitas Rozzano, Italy

Case Scenario: Perioperative Airway Management of a Patient with Tracheal Stenosis

TRACHEAL stenosis is a rare but a life-threatening condition and is caused by congenital problems, postintubation injury, trauma, tracheal tumor, and compression of the trachea by tumor. Although accurate prevalence of this condition is unknown, an incidence of 4.9 cases per million per year is estimated for postintubation tracheal stenosis. A stenosis commonly occurs at the cuff of the tube (intrathoracic trachea) or at the level of the tracheostomy stoma (extrathoracic trachea). Anesthesia of a patient with tracheal stenosis is challenging for anesthesiologists. Depending on the severity and location of the stenosis and the type of surgical procedure, there may be a variety of choices for perioperative airway management such as a facemask, laryngeal mask airway, an tracheal intubation tube, cardiopulmonary bypass, and extracorporeal membrane oxygenation. The American Society of Anesthesiologists practice guidelines for management of the difficult airway primarily focus airway problems caused at the extrathoracic airway and may not be helpful, particularly for managing patients with intrathoracic tracheal stenosis. In this case scenario, we present a patient with severe intrathoracic tracheal stenosis, who required surgery for a lumbar fracture in the prone position. Various airway management strategies and the actual management used are discussed.

The Management of Postoperative Pain with Continuous Intravenous Fentanyl Infusion

The Management of Postoperative Pain with Continuous Intravenous Fentanyl Infusion

Comparison of Sufentanil versus Fentanyl in Ventilated Term Neonates

Increasingly frequent applications of opioid analgesics in neonatal intensive care require the evaluation of efficacy and side effects. Mechanically ventilated term neonates were consecutively enrolled. In a double-blind randomized trial 20 newborns received a continuous intravenous infusion of fentanyl (n=10) or sufentanil (n=10) in an assumed equipotent dose of 7:1. The analgesic dose was individually adjusted according to sedation scores. The period between cessation of analgesic medication and successful extubation (weaning time), adverse drug effects and urinary cortisol concentrations were evaluated. No significant difference of weaning time was seen between fentanyl and sufentanil group (mean weaning time (+/-SD) of fentanyl group 520+/-381 min, median 380 min; sufentanil group 585+/-531 min, median 405 min, p=0.78, 2-tailed U-Test, Mann and Whitney). The mean opioid dose resulted in a 10:1 ratio (fentanyl 4.11 microg/(kg x h) vs sufentanil 0.41 microg/(kg x h)). We found no marked differences in sedation levels, blood pressure, heart rate, oxygenation index, co-medication or urinary cortisol levels. In both groups similar adverse effects were assessed including respiratory depression, mild withdrawal symptoms or decrease of gastrointestinal motility. In our study sufentanil did not reduce the weaning period in ventilated term neonates when compared to fentanyl. The equipotent dose ratio for fentanyl/sufentanil was 10:1. According to sedation scores both substances provided effective pain and stress protection.

Effects of Premedication With Tiletamine/Zolazepam/Medetomidine During General Anesthesia Using Sevoflurane/Fentanyl in Swine Undergoing Pancreas Transplantation

Objective To assess cardiac and hemodynamic responses and body temperature during long-term general anesthesia using sevoflurane/fentanyl after premedication with a tiletamine/zolazepam/medetomidine combination in swine undergoing experimental pancreas transplantation. Materials and methods Twelve Landrace female pigs of means weight 46.4 ± 5.1 kg were premedicated by intramuscular administration of tiletamine/zolazepam (3.5 mg/kg), medetomidine (0.03 mg/kg), and atropine (0.02 mg/kg), before anesthesia with 0.75 minimum alveolar concentration sevoflurane and continuous intravenous fentanyl infusion (5.7 ± 0.7 μg/kg/h). Assessment of heart rate, arterial blood pressure, and temperature in pigs undergoing allogenic pancreas transplant surgery were registered at the start of anesthesia (T0), as well as at 60 (T60), 120 (T120), and 180 (T180) minutes after T0, and finally at the end of anesthesia (T anesthesia end), when we switched off the sevoflurane vaporizer. Analysis of variance was used to determine differences between times with P < .05 considered significant. Results are given as mean values ± standard deviations. Results Arterial blood pressure significantly decreased from T120 to the end of anesthesia, while a significantly decreased heart rate was only evident at T60. Body temperature decreased significantly from T60 to the end of anesthesia. These decreases, however, lacked clinical relevance; all parameters were within normal range. No major anesthetic complications were observed in this study. Conclusions The administration of a tiletamine/zolazepam/medetomidine combination as premedication in swine subjected to pancreas transplantation allowed for a safe reduction of sevoflurane/fentanyl requirements during long-term general anesthesia. Despite arterial blood pressure and body temperature evidencing a decrease during anesthetic maintenance, all parameters remained within normal range values.

Prospective sonographic evaluation of fentanyl side effects on the neonatal gallbladder

In an effort to minimise the stress and pain of mechanically ventilated neonates, the application of opioids has increased markedly. Abdominal adverse effects of opioid analgesics are constipation and increased pressure in the biliary system. Our aim was to evaluate the impact of continuous intravenous infusion of fentanyl on the volume of the neonatal gallbladder and to assess potential gastrointestinal side effects. We prospectively matched pairs of 40 mechanically ventilated neonates (28-42 gestational weeks) under total parenteral nutrition and midazolam sedation. One group (20 patients) received continuous fentanyl infusions (dose 0.5-2 microg kg(-1) h(-1)) the other group (20 patients) served as controls. Sonographic measurements of gallbladder length, depth and width were performed to calculate gallbladder volume using the ellipsoid method. Repeated ultrasound images, date of meconium release and serum bilirubin levels were documented. Fentanyl application was not associated with gallbladder sludge/stones, gallbladder hydrops, hyperbilirubinemia or prolonged meconium release. Neonatal gallbladder length, width and volume did not differ significantly (data expressed as mean, standard deviation, median, interquartile range: length (cm) 3.16+/-0.68, 3.3, 0.675 vs 3.06+/-0.62, 3.3, 1.1; P=0.645; width (cm) 1.02+/-0.23, 1.0, 0.28 vs 0.89+/-0.27, 0.9, 0.38, P=0.12; volume (cm(3)) 1.52+/-0.67, 1.7, 0.86 vs 1.22+/-0.77, 1.09, 1.19, P=0.20). In our study fentanyl caused no major complications in the biliary system and intestine of ventilated preterm and term neonates. Sonographic investigations of the gallbladder under fentanyl treatment may be dispensable. Further investigations are required to assess adverse gastrointestinal effects.