Fentanyl Infusion Research Articles

FENTANYL-INDUCED PERSISTENT ENCEPHALOPATHY

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Fentanyl is a synthetic opioid routinely used for sedation and analgesia in the intensive care unit (ICU). Though typically safe when used vigilantly for ICU-level care, it can sometimes cause serious adverse effects such as acute encephalopathy that usually improve with supportive care. We present a rare case of persistent encephalopathy caused by fentanyl. CASE PRESENTATION: An 85-year-old functionally independent woman with a history of chronic obstructive pulmonary disease (COPD) on 2 L oxygen, hypertension, and hypothyroidism presented with shortness of breath and dry cough for four days. She was intubated and mechanically ventilated for worsening respiratory distress and hypercapnia. She required deep sedation with maximum doses of fentanyl infusion 200 mcg/hr and propofol infusion 60 mcg/kg/min, and vasopressor support with norepinephrine for two days to maintain her blood pressure. Sputum cultures grew Haemophilus influenza. She was treated with 7 days of intravenous levofloxacin for tracheobronchitis and COPD exacerbation. She also received intravenous methylprednisolone and breathing treatments. Her respiratory status gradually improved and she was weaned down to minimal ventilator FiO2 and PEEP and sedation in five days, but she stayed unresponsive. Seven days off sedation, she had a partial return of consciousness but had altered mentation, quadriplegia, and absence of reflexes bilaterally. She showed minimal response to painful stimuli in all limbs. CT and MRI of the head and C-spine showed no acute pathology. Cerebrospinal fluid analysis and cultures ruled out infectious (including viral, bacterial, and fungal) etiologies. 12-hour EEG was consistent with metabolic encephalopathy. After multidisciplinary evaluation, her encephalopathy was attributed to fentanyl. Patient was eventually extubated after 16 days. One month later, she had mild improvement of neurological status with orientation only to person. She was able to slightly squeeze examiner's fingers in both hands, and foot plantar and dorsiflexion was 4/5 bilaterally with the rest of motor strength 0/5 in all extremities. She was discharged to a nursing home with unchanged neurological status. DISCUSSION: Fentanyl has a rapid onset and short duration of action making it sedation of choice in ICU. Acute encephalopathy is infrequently associated with other synthetic opioids like oxycodone and methadone [1,2]. Fentanyl uncommonly causes delayed hypoxic leukoencephalopathy which develops few days to weeks after exposure [3]. Acute persistent encephalopathy from fentanyl is rare and can lead to significant functional impairment. CONCLUSIONS: It is important for clinicians to be aware of persistent encephalopathy caused by fentanyl. Sedation should be used with caution especially in elderly patients. Intermittent pushes or shorter duration of use may prevent this rare complication. REFERENCE #1: Morales Odia Y, Jinka M, Ziai WC. Severe leukoencephalopathy following acute oxycodone intoxication. Neurocrit Care. 2010;13(1):93-97. REFERENCE #2: Haghighi-Morad M, Naseri Z, Jamshidi N, Hassanian-Moghaddam H, Zamani N, Ahmad-Molaei L. Methadone-induced encephalopathy: a case series and literature review. BMC Med Imaging. 2020;20(1):6. REFERENCE #3: Kim J, Hyung SW, Seo J, Lee H, Yu HJ, Sunwoo MK. Delayed post-hypoxic leukoencephalopathy caused by fentanyl intoxication in a healthy woman. Dement Neurocognitive Disord. 2020;19(4):170-172. DISCLOSURES: No relevant relationships by Qasim Jehangir, source=Web Response No relevant relationships by Yi Lee, source=Web Response No relevant relationships by Ali Najar, source=Web Response No relevant relationships by Jonathan Toot, source=Web Response

Периоперационный менеджмент хирургической коррекции сколиотической деформации позвоночника и применение фармакокинетических и фармакодинамических подходов в дозировке препаратов для анестезии

Актуальность. Анестезиология давно стала мультидисциплинарной наукой и приобретает все больше черт периоперационной медицины. Подтверждением этого являются разработка и имплементация протоколов ERAS в анестезиологию. Современные достижения в понимании принципов фармакодинамики и фармакокинетики позволяют точно подобрать дозу для достижения нужной концентрации в месте действия, избегая слишком глубокой анестезии, и создания условий для адекватной работы нейрофизиологического мониторинга во время оперативного вмешательства. Цель исследования: адаптировать периоперационный менеджмент сколиотической деформации позвоночника к рекомендациям ERAS и ввести фармакокинетические и фармакодинамические подходы при дозировке препаратов для обезболивания и седации. Материалы и методы. Было проведено 40 плановых операционных вмешательств по поводу сколиотических и других деформаций позвоночника. Пациенты были разделены на две группы в зависимости от метода дозирования и введения фентанила интраоперационно: 1-я группа — пациенты, которым фентанил вводили каждые 15–20 мин в дозе 100–200 мкг, и 2-я группа — пациенты, которым фентанил вводили инфузионно до достижения концентрации в месте действия 3–6 нг/мл. Оценивалось количество введенного фентанила за час операционного вмешательства, а также фиксировалось время отлучения пациента от аппарата искусственной вентиляции легких (ИВЛ). Результаты. При дозировке фентанила по целевой концентрации и инфузии его количество составляло 250 ± 50 мкг в час, что значительно отличалось от количества введенного препарата путем болезненных инъекций — 350 ± 50 мкг в час. Продолжительность послеоперационной ИВЛ при введении фентанила инфузионно по целевой концентрации была в пределах 14,2 ± 2,1 мин, а при болюсном введении достигала 25,3 ± 6,8 мин. Выводы. В работе предложены и обоснованы необходимость имплементации протоколов ERAS для коррекции сколиозов и внедрение фармакокинетического и фармакодинамического подходов при дозировке препаратов для анестезии.

Serratus Anterior Plane Block in Pediatric Patients Undergoing Thoracic Surgeries: A Randomized Controlled Trial

This study was designed to evaluate the efficacy and safety of serratus anterior plane block (SAPB) as an analgesic technique for thoracotomies in pediatric patients. Double-blinded randomized controlled trial. A single-center study at Aboelrish Pediatric Hospital, one tertiary hospital of Cairo University Hospitals. Seventy pediatric patients aged six months-to-three years scheduled for thoracotomies. Patients were randomized into two groups, group SF and group F. Group SF received an ultrasound-guided SAPB (n=35), whereas group F (n=35) did not. All groups received an intraoperative fentanyl infusion (at 0.5 μg/kg /h). The primary outcome was the total dose of postoperatively administrated fentanyl in the first 24 hours. The secondary outcomes included the total dose of intraoperative additional fentanyl boluses; time of the first postoperative rescue analgesia; and postoperative Face, Legs, Activity, Cry, Consolability scale (FLACC) score values. The main results of this study showed that the administrated fentanyl in the 24 hours postoperatively was significantly lower in SF group than in F group (p value ˂ 0.001). In addition, significant decreases of the postoperative FLACC pain score (p value ˂ 0.001), reduction of intraoperative fentanyl consumption (p value ˂ 0.001), and delay of the first rescue analgesia (p value ˂ 0.001) were recorded in SF group in relation to F group without significant complications in both groups. Serratus anterior plane block can provide a safe, effective, and easy-to-perform regional technique for children undergoing thoracotomies.

Comparison of Intraoperative Infusion of Remifentanil Versus Fentanyl on Pain Management in Patients Undergoing Spine Surgery: A Double Blinded Randomized Clinical Trial.

BackgroundRemifentanil is an ultra-short-acting opioid which facilitates hemodynamic management. However, there are concerns about postoperative Remifentanil hyperalgesia because of its potent fast onset and offset.ObjectivesThe aim of this study was to determine visual analog scale (VAS), postoperative pain, and morphine used in two groups after spine surgery.MethodsIn this randomized clinical trial study, 60 patients aged 18 - 60 years old, according to the American Society of Anesthesiology (ASA) I - II, who underwent spinal canal stenosis or scoliosis surgery, were divided into two groups. In the control group, patients received 0.07 - 0.1 µg/kg/h intraoperative Fentanyl infusion, and in the intervention group 0.1 - 0.2 µg/kg/min remifentanil was infused during the surgery. Both groups received 15 mg/kg intravenous Acetaminophen 20 minutes before the end of the surgery. Postoperative pain score and morphine consumption were measured 6, 12, 24, and 48 hours after discharge from the post-anesthesia care unit (PACU).ResultsDuring the first 12 hours, VAS and morphine consumption were significantly higher in remifentanil group (P < 0.001). However, no significant difference was found between the two groups in morphine consumption 12 - 48 hours after surgery.ConclusionsThese findings suggest that Remifentanil infusion during surgery may increase postoperative pain. Also, VAS and morphine consumption were higher during the first 12 hours.

Early Outcomes Following off-Pump Coronary Artery Bypass Surgery under General Anaesthesia with and without High Thoracic Epidural Analgesia: A Comparative Study

Introduction: Reduction of postoperative morbidity by providing optimal pain relief and improving overall quality of care is an important goal of modern anaesthesia practice. The aim of this prospective, randomized, open, controlled study is to investigate the impact of high thoracic epidural analgesia on early clinical outcomes in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. Methodology: After obtaining the institutional ethics committee approval and written informed consent from all patients, 80 patients of either sex, aged 40 – 70 years, scheduled for elective primary OPCAB surgery were randomized into two groups. Group I received 4 mL of an epidural bolus of 1% ropivacaine and fentanyl 100 µg followed by ropivacaine 1% and fentanyl 5 µg/mL infusion for 72 h at 3–5 mL/h postoperatively. Analgesia in the Group II was provided with a continuous IV fentanyl infusion. Patients were given rescue analgesic (inj Tramadol intravenous) when VAS score is &gt;40 in the postoperative period. Results: VAS score, need for rescue analgesics and incidence of postoperative arrythmia were significantly lower in Group I specially for first twenty four hours postoperatively. Time for extubation and length of postoperative ICU stay were found similar in both the groups. Incidence of other outcomes found to be not significant. Conclusion: The pain scores, analgesic requirements and incidence perioperative arryrhmias were significantly less in Group I compared to Group II, but we could not be able to find any significant difference in time for extubation and length of ICU stay, neither in incidence of postoperative MI, CVA, renal failure, blood transfusion and death.

Hirudotherapy (medicinal leeches) for treatment of upper airway obstruction in a dog

To describe upper airway obstruction (UAO) in a dog treated with medicinal leeches (hirudotherapy) as an ancillary therapy to hasten recovery. A 10-month-old neutered female Mastiff presented for acute respiratory distress. On admission, the dog was tachycardic, cyanotic, and orthopneic; stridor was audible. A 10-cm soft tissue swelling in the right ventral cervical region and bruising around the rostral mandible were noted. At the time of endotracheal intubation, the trachea was deviated to the right as a consequence of severe soft tissue swelling that was contiguous with the sublingual hematoma and cervical region, causing loss of visualization of the arytenoids. A computed tomography with contrast scan of the head, neck, and thorax was performed, showing severe soft tissue swelling of the tongue, obliteration of the common pharyngeal/laryngeal regions from suspected hemorrhage, and rightward displacement of pharynx, larynx, and proximal trachea. Marked diffuse bronchial/bronchiolar thickening associated with bronchiolectasis and diffuse opacification of the pulmonary parenchyma with regions of consolidation were noted. The dog was minimally hypercoagulable on thromboelastography. The imaging results together with results of bronchoalveolar lavage cytology supported a comorbidity of eosinophilic bronchopneumopathy. Intubation was maintained with infusions of propofol and fentanyl, with minimal changes in oropharyngeal swelling within the first 18hours of treatment. Medicinal leeches were then applied to the sublingual and cervical regions. There was continued slow bleeding from the sites of leech detachment, and the dog was able to be extubated at 44hours, followed by hospital discharge. Leeches are utilized in human medicine for treatment of UAO. Although UAO from hemorrhage has been described in dogs, this is the first report of medicinal leeches (Hirudo verbana) as complementary treatment for sublingual hematoma that contributed to UAO.

A retrospective study comparing analgesic efficacy of ultrasound-guided serratus anterior plane block versus intravenous fentanyl infusion in patients with multiple rib fractures.

Background and Aims:Inadequately managed pain due to multiple rib fractures (MRFs) can lead to atelectasis, pneumonia, prolonged ICU stay thereby leads to significant morbidity, morbidity and cost of treatment. Opioids, non-steroidal anti-inflammatory drugs and regional anaesthesia techniques like thoracic epidural or paravertebral blocks, intercostal nerve blocks are used to manage pain. Serratus anterior plane block (SAPB) is an ultrasound (US) guided interfascial plane block which has been used in managing pain due to MRFs. In this retrospective study, we compared analgesic efficacy and 24 hr fentanyl consumption in patients with MRFs who were managed with continuous SAPB versus patients who were managed with fentanyl infusion alone.Material and Methods:After Institutional Ethics Committee approval, we retrospectively collected data of 72 patients (38 in SAPB group and 34 in fentanyl group). Demographic data, VAS scores and 24 hrs fentanyl consumption was analysed in both groups.Results:There were statistically significant lower pain scores in patients of SAPB group when compared to that of fentanyl group (p=0.001) and in 24 hrs fentanyl consumption in patients who received continuous SAPB versus that in fentanyl group(p=0.001). No complications were observed in patients who received US guided SAPB.Conclusion:US guided SAPB is an opioid sparing, effective interfascial plane block which is safe and should be considered early in all patients who sustain MRFs. Continuous SAPB by placing a catheter can provide pain relief for longer duration, facilitate early mobilization, physiotherapy and early ICU discharge.

Analgosedation: The Use of Fentanyl Compared to Hydromorphone.

BackgroundThe 2018 Society of Critical Care Medicine guidelines on the “Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU” advocate for protocol-based analgosedation practices. There are limited data available to guide which analgesic to use. This study compares outcomes in patients who received continuous infusions of fentanyl or hydromorphone as sedative agents in the intensive care setting.MethodsThis retrospective cohort study evaluated patients admitted into the medical intensive care unit, the surgical intensive care unit, and the cardiac intensive care unit from April 1, 2017, to August 1, 2018, who were placed on continuous analgesics. Patients were divided according to receipt of fentanyl or hydromorphone as a continuous infusion as a sedative agent. The primary endpoints were ICU length of stay and time on mechanical ventilation.ResultsA total of 177 patients were included in the study; 103 received fentanyl as a continuous infusion, and 74 received hydromorphone as a continuous infusion. Baseline characteristics were similar between groups. Patients in the hydromorphone group had deeper sedation targets. Median ICU length of stay was eight days in the fentanyl group compared to seven days in the hydromorphone group (p = 0.11) and median time on mechanical ventilation was 146.47 hours in the fentanyl group and 122.33 hours in the hydromorphone group (p = 0.31). There were no statistically significant differences in the primary endpoints of ICU length of stay and time on mechanical ventilation between fentanyl and hydromorphone for analgosedation purposes.ConclusionNo statistically significant differences were found in the primary endpoints studied. Patients in the hydromorphone group required more tracheostomies, restraints, and were more likely to have a higher proportion of Critical Care Pain Observation Tool (CPOT) scores > 2.

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.

Dose‐dependent multiple physiologic effects of systemic fentanyl in awake adult goats

It is well known that opioid analgesics induce life-threatening respiratory depression. A few studies have also documented additional deleterious effects of opioids on multiple physiologic functions. Moreover, there are reports of interindividual variation in susceptibility, magnitude, and duration of physiologic effects of opioids such as fentanyl. Here we tested the dose-dependent effects of intravenous injected fentanyl on physiologic functions in 7 awake, adult goats. Goats were instrumented for recording of multiple cardiorespiratory variables including respiratory pump and airway muscle activity. After a 30-minute control period, 0, 10, 20, or 50 µg/kg fentanyl was infused intravenously. We found that rapid IV infusion of fentanyl over 2 min caused a dose-dependent decrease in minute ventilation due to dramatic suppression of breathing frequency within 5 min after IV injection. These effects were coupled with dose-dependent increases in VT, which represents a more human like ventilatory response to opioids. The major suppression of ventilation occurred in 5 of the 7 goats, whereas in 2 of the goats IV fentanyl injections increased breathing frequency in a dose-dependent manner. This variation in ventilatory response to opioids agrees with findings that in a subset of humans, opioids have an excitatory effect on physiologic functions (Br. J. Anaesth 81, 1998). The suppression of ventilation seen in the majority of goats is transient, lasting for 3-10 minutes post-injection and is accompanied by an increased or normal VT up to 30-90 minutes. Over the initial 10 minutes after injection, there were obstructive and central apneas often exceeding one minute resulting in arterial hypoxemia (PaO2<50 mmHg) and hypercapnia (PaCO2>50mmHg). Heart rate was decreased for up to 15 minutes following 50µg/kg injection, whereas arterial blood pressure was increased for at least 90 minutes post-injection. Particularly over the initial minutes after 50µg/kg, fentanyl infusion decreased the duration but increased the intensity of diaphragm and intercostal muscle activity while increasing tonic activity of abdominal and airway muscles. Infusion of naloxone before or after infusion of fentanyl prevented or reversed the acute and delayed physiologic effects induced by fentanyl. Injection of Naloxone alone had no effect on physiological measures of goats. We conclude that goats have multiple dose- and individual-dependent physiologic responses to systemic infusion of fentanyl. Furthermore, our reversal data suggests the effects of fentanyl in goats are likely mediated by activation of µ-opioid receptors.

ANAESTHETIC MANAGEMENT OF SURGERY FOR ORAL CANCER IN A MORBIDLY OBESE PATIENT WITH DIFFICULT AIRWAY AND OBSTRUCTIVE SLEEPAPNOEA - A CASE REPORT

We are reporting a case of a 39 year old morbidly obese gentleman (117Kg BMI:38.9) with history of obstructive sleep apnoea (OSA) who was presented for surgery for carcinoma tongue under general anaesthesia (GA). As the patient had features strongly suggestive of difcult intubation and difcult ventilation, we decided to secure his airway under awake bre optic bronchoscopy (FOB). General anaesthesia was induced as per routine departmental protocol. Fentanyl infusion at 20 mcg/hr for both perioperative analgesia and endotracheal tube tolerance. Patient was extubated on POD 1 and given non Invasive ventilation as he was extremely drowsy and not maintaining a saturation above 91% in spite of oxygen supplementation. Since we judged this patient to be a typical case of cannot intubate, cannot ventilate situation, we decided against giving a trial laryngoscopy after induction and instead opted to proceed straight away with awake intubation under airway anaesthesia.

Evaluation of whether acepromazine maleate causes fentanyl to decrease the minimum alveolar concentration of isoflurane in cats.

To determine whether isoflurane-anesthetized cats with demonstrated resistance to the immobilizing effects of fentanyl would exhibit naltrexone-reversible sparing of the minimum alveolar concentration (MAC) of isoflurane when fentanyl was coadministered with the centrally acting catecholamine receptor antagonist acepromazine. 5 healthy male purpose-bred cats. Anesthesia was induced and maintained with isoflurane in oxygen. Baseline isoflurane MAC was measured by use of a standard tail clamp stimulus and bracketing study design. Afterward, fentanyl was administered IV to achieve a plasma concentration of 100 ng/mL by means of target-controlled infusion, and isoflurane MAC was remeasured. Next, acepromazine maleate (0.1 mg/kg) was administered IV, and isoflurane MAC was remeasured. Finally, isoflurane concentration was equilibrated at 70% of the baseline MAC. Movement of cats in response to tail clamping was tested before and after IV bolus administration of naltrexone. Physiologic responses were compared among treatment conditions. Isoflurane MAC did not differ significantly between baseline and fentanyl infusion (mean ± SD, 1.944 ± 0.111% and 1.982 ± 0.126%, respectively). Acepromazine with fentanyl significantly decreased isoflurane MAC to 1.002 ± 0.056% of 1 atm pressure. When isoflurane was increased to 70% of the baseline MAC, no cats moved in response to tail clamping before naltrexone administration, but all cats moved after naltrexone administration. Acepromazine caused fentanyl to decrease the isoflurane MAC in cats that otherwise did not exhibit altered isoflurane requirements with fentanyl alone. Results suggested that opioid-mediated increases in brain catecholamine concentrations in cats counteract the opioid MAC-sparing effect.

Rationale for analgesia to prevent postoperative hyperalgesia in children, according to the morphological study of skin in the wound

In the article, morphological changes of skin in the area of postoperative wound are displayed. It was discovered that continuous infusion of high-dose fentanyl (10–20 mcg/kg/h) for analgesia in the early postoperative period in children operated on for tumors of abdominal cavity can result into opiod-induced hyperalgesia, which is followed by skin morphological changes around the postoperative wound with the development of necrosis in it center with expressed perifocal reactive changes in the form of severe inflammation, and significant violations of microcirculation with the formation of small nerve fibers on day 14. In its turn, using TAP-block and combined spinal-epidural analgesia showed small perineural edema. The fragmentation of nerve fibers was not determined, which indicates the absence of development of postoperative hyperalgesia. Ketamine infusion results into negligible perineural edema and reduction of postoperative hyperalgesia.

Comparative Study between Dexmedetomidine vs Midazolam-Fentanyl on Emergence Agitation in Children Undergoing Cochlear Implantation in Sohag University Hospital

ABSTRACT Background: Surgery of cochlear implantation is a great advance in otology for patients with deaf mutism, but it carries a great challenge to the anesthesiologist. Objective: The aim of the current work was to compare effect of bolus Dexmedetomidine infusion versus bolus Midazolam- fentanyl infusion as regards; emergence agitation & recovery time, hemodynamics, postoperative pain and complication. Patient and Methods: This study included a total of 40 pediatric patients (ASA I or II), undergoing cochlear implantation, attending at Sohag University Hospital. They were randomized divided into dexmedetomidine (D) group and midazolam (M) group. Results: There was no significant difference between both groups as regard intraoperative mean blood pressure. There was a significant difference at discharge time. There was statistically insignificant decrease in heart rate (HR) in group D than M group. There was statistically significant difference at 1 min and discharge measurements. There was a highly significant difference between both groups as the time for recovery being more rapid in D group than in M group. Mask Acceptance Scale (MAS) was better within D group than M group without statistically significant difference. There was a no significant difference in emergence agitation between both groups. There was no significant difference between both groups as regard objective pain score. As regard nausea and vomiting, there was a highly significant difference between both groups. Conclusion: It could be concluded that dexmedetomidine infusion in cochlear implantation in pediatric patients was equal as midazolam-fentanyl in inducing hypotension, emergence agitation and giving post-operative analgesia. However, dexmedetomidine infusion is better as regardrapid recovery without inducing nausea and vomiting.

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

To determine the cardiopulmonary effects of IV administration of fentanyl to cats anesthetized with isoflurane and during anesthetic recovery with concurrent administration of acepromazine or dexmedetomidine. 6 healthy adult cats. Cats received an IV bolus (5 μg/kg) followed by an IV infusion (5 μg/kg/h) of fentanyl for 120 minutes during isoflurane anesthesia and for 30 minutes after discontinuing isoflurane. Cats were randomly assigned in a crossover study to receive acepromazine (0.05 mg/kg) or dexmedetomidine (2.5 μg/kg), IV, when isoflurane was discontinued. Cardiopulmonary data were obtained during anesthesia and for 30 minutes during the anesthetic recovery period. The administration of fentanyl during isoflurane anesthesia resulted in a transient increase in arterial blood pressure, mean pulmonary artery pressure, and oxygen delivery. Compared with values during isoflurane anesthesia, administration of dexmedetomidine during anesthetic recovery resulted in significant decreases in cardiac index, stroke index, and oxygen delivery and significant increases in arterial, central venous, and mean pulmonary artery pressures; systemic vascular resistance index; and oxygen extraction ratio. Administration of acepromazine resulted in increases in heart rate, cardiac index, oxygen uptake, and oxygen extraction ratio. Oxygen extraction ratio did not differ between acepromazine and dexmedetomidine. Fentanyl transiently improved indices of cardiopulmonary performance when administered to healthy cats anesthetized with isoflurane. The cardiovascular effects of acepromazine and dexmedetomidine in healthy cats receiving fentanyl during recovery from isoflurane anesthesia differed, but measured cardiopulmonary parameters remained within acceptable limits.

Analysis of fentanyl pharmacokinetics, and its sedative effects and tolerance in critically ill children.

Fentanyl pharmacokinetic and pharmacodynamic data are limited in mechanically ventilated children. This study aimed to assess the fentanyl pharmacokinetics (PK), the sedation outcome, and the development of tolerance in children receiving fentanyl continuous infusion. This study included children admitted to the pediatric or cardiovascular intensive care unit between January 1 and October 31, 2016, who were >30days to <18years of age, receiving ventilatory support via endotracheal tube or tracheostomy, and receiving a fentanyl infusion. Population PK analysis was performed using a nonlinear mixed-effects model. The relationship between initial sedation outcome using State Behavioral Scale (SBS) and fentanyl exposure was assessed, and the observations consistent with tolerance were described. Seventeen children, with a median age of 0.83years (range: 0.1-12) and weight of 8.7kg (range: 3.4-52), were included. The fentanyl PK was adequately described by a weight-based allometry model with the power of 0.75 for clearance (CL=89.8 L/hr/70kg) and distributional CL, and 1 for volumes of distribution. In infants <6.6months, age was an additional factor for CL (31.4 L/h/70kg) to account for age-related maturation. Seven of twelve nonparalyzed patients achieved goal sedation, defined as >80% of SBS scores ≤0 per 24h, on the first day of fentanyl infusion with a median plasma concentration of 1.29ng/ml (interquartile range: 0.78-2.05). Eight of the nine tolerant patients developed tolerance within a day of reaching goal sedation. Different weight-based fentanyl dosing rates may be required for infants and children of different ages to achieve similar plasma concentrations. Using SBS scores may guide the dosing titration of fentanyl that resulted in plasma concentrations within the therapeutic range of 1-3ng/ml. For those who developed tolerance to fentanyl and/or a sedative, it was noted one day after goal sedation was achieved.

Thromboelastometry-based algorithm and transfusion management during orthotopic liver transplantations

Thromboelastometry-based algorithm and transfusion management during orthotopic liver transplantations

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

Abstract 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 &lt; 0.001). There was a significant change in mean arterial blood pressure (mm Hg) between the groups at pin fixation Group F (104.70 ± 9.18) and Group S (92.88 ± 6.92) (P &lt; 0.001). A significant reduction in pain and intraoperative fentanyl requirements was also seen. Emergence from anesthesia was significantly longer in Group F as compared to Group S (P &lt; 0.001). No group had any significant complication. Conclusion: SNB is a reasonably safe and effective means for smooth control over hemodynamics and lesser intraoperative analgesic requirements compared to the fentanyl infusion in adult patients undergoing supratentorial craniotomies.

Conversion From Continuous Infusion Fentanyl to Continuous Infusion Hydromorphone in the Pediatric Intensive Care Unit.

Opioid rotations from fentanyl to hydromorphone may reduce opioid/sedative exposure in critically ill children. The primary objective was to determine the conversion percentage from fentanyl to hydromorphone infusions using equianalgesic conversions (0.1 mg fentanyl = 1.5 mg hydromorphone). Secondary objectives included identification of the median time and hydromorphone rate at stabilization (defined as the first 24-hour period no hydromorphone rates changed, 80% of State Behavioral Scale [SBS] scores between 0 and -1, and <3 hydromorphone boluses administered). Additional outcomes included a comparison of opioid/sedative requirements on the day of conversion versus the three 24-hour periods prior to conversion. This retrospective study included children <18 years old converted from fentanyl to hydromorphone infusions over 6.3 years. Linear mixed models were used to determine if the mean cumulative opioid/sedative dosing differed from the day of conversion versus three 24-hour periods prior to conversion. A total of 36 children were converted to hydromorphone. The median conversion percentage of hydromorphone was 86% of their fentanyl dose (interquartile range [IQR] = 67-100). The median hydromorphone rate at stabilization was 0.08 mg/kg/h (IQR = 0.05-0.1). Eight (22%) were stabilized on their initial hydromorphone rate; 8 (22%) never achieved stabilization. Patients had a significant decrease in opioid dosing on the day of conversion versus the 24-hour period prior to conversion but no changes in sedative dosing following conversion. A median 14% fentanyl dose reduction was noted when transitioning to hydromorphone. Further exploration is needed to determine if opioid rotations with hydromorphone can reduce opioid/sedative exposure.

Continuous infusion of fentanil, dexmedetomidine or maropitant in dogs undergoing to ovariohysterectomia

The aim of this study was to compare the analgesic effects of continuous infusion of fentanyl, dexmedetomidine, or maropitant. The animals received pre-anesthetic medication and anesthetic induction. Subsequently, continuous infusion of drugs was instituted, distributed in the following groups: fentanyl, dexmedetomidine, and maropitant. During the surgical procedure, the analgesic effects were evaluated by recording the cardiorespiratory parameters at the moments of greatest pain stimulus. When evaluating analgesic effects, the maropitant group showed greater stability in cardiorespiratory parameters compared to the fentanyl and dexmedetomidine group. From this study, it is suggested that continuous infusion of maropitant has analgesic effects similar to fentanyl and greater than dexmedetomidine.