Plasma Remifentanil Concentrations Research Articles

Prolonged Anesthesia Induction to Delivery Time Did Not Influence Plasma Remifentanil Concentration in Neonates.

Remifentanil, in combination with etomidate and sevoflurane, is commonly used in clinics for general anesthesia induction in cesarean section (CS). This study aimed to evaluate the correlation between the induction to delivery (I-D) time and neonatal plasma drug concentration and anesthesia, as well as its effects on neonates. Fifty-two parturients in whom general anesthesia was induced for CS were divided into group A (I-D<8 min) and group B (I-D≥8 min). Maternal arterial (MA), umbilical venous (UV), and umbilical arterial (UA) blood samples were collected at delivery to analyze the remifentanil and etomidate concentrations using liquid chromatography-tandem mass spectrometry. There were no statistically significant differences between the two groups in terms of plasma concentrations of remifentanil in the MA, UA, and UV blood (P > 0.05). The plasma concentration of etomidate in MA and UV was higher in group A than that in group B (P<0.05), whereas the UA/UV ratio of etomidate was higher in group B than that in group A (P<0.05). The Spearman rank correlation test showed no correlation between the I-D time and plasma remifentanil concentration in the MA, UA, and UV plasma (P>0.05). The concentrations of etomidate in the MA and UV were negatively correlated with the I-D time (P < 0.05). Prolonged I-D time did not significantly influence the maternal or neonatal plasma concentration of remifentanil. It is safe to administer remifentanil target-controlled infusion in combination with etomidate and sevoflurane for general anesthesia induction during CS.

The effect of remifentanil infusion on sevoflurane minimum alveolar concentration–no movement (MACNM) and bispectral index in dogs

ObjectiveTo determine the effect of remifentanil infusion on the minimum alveolar concentration of sevoflurane preventing movement (SEVOMACNM) and bispectral index (BIS) in dogs. Study designProspective, unmasked study. AnimalsA total of 10 adult Beagle dogs weighing 9.0 ± 1.1 kg. MethodsDogs were anesthetized with sevoflurane and baseline SEVOMACNM was determined. Remifentanil was infused at 5, 10 and 20 μg kg–1 hour–1, in sequence, with 20 minutes washout between infusions. Variables monitored throughout anesthesia included heart rate (HR), oscillometric blood pressure, end-tidal partial pressure of carbon dioxide, end-tidal sevoflurane concentration (Fe′Sevo) and BIS. SEVOMACNM after remifentanil infusion (SEVOMACNM-REMI) determination started 20 minutes after the start of each infusion. Venous blood samples were collected for plasma remifentanil concentration determination at baseline, SEVOMACNM-REMI determination time points, and 20 minutes after each infusion was stopped. A mixed model analysis was used to determine the effect of remifentanil infusion on response variables. The relationships between BIS and Fe′Sevo, plasma remifentanil concentrations and the percentage decrease in baseline SEVOMACNM were evaluated (p < 0.05). ResultsThe overall SEVOMACNM at baseline was 2.47 ± 0.11%. Addition of remifentanil at all infusion rates significantly decreased SEVOMACNM, but the medium and high doses resulted in significantly greater decreases in SEVOMACNM than the lower dose. There was no difference in SEVOMACNM percentage change between infusions 10 and 20 μg kg–1 hour–1. Plasma remifentanil concentrations were significantly different in all infusion rates. Baseline BIS value was 70 ± 1 and was lower than the BIS values recorded during all remifentanil infusions. BIS values were not significantly different among infusion rates. HR was lower and mean arterial pressure was higher during remifentanil infusions than at baseline. Conclusions and clinical relevanceAll remifentanil infusions decreased SEVOMACNM in dogs. Remifentanil infusion at any rate studied did not reduce BIS values.

Reliability of the Minto model for target-controlled infusion of remifentanil during cardiac surgery with cardiopulmonary bypass

BackgroundThe Minto pharmacokinetic model is used for target-controlled infusion of remifentanil. The reliability of this model has never been evaluated during normothermic cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study was to assess the predictive performance of the model during CPB to determine its reliability during cardiac surgery. MethodsThis was a single-centre observational study. Arterial blood samples were drawn at five time points: T1, after tracheal intubation; T2, immediately before CPB; T3, 10 min after starting CPB; T4, 45 min after starting CPB; T5, 10 min after weaning off CPB. Prediction error (PE) and absolute prediction error (APE) were calculated for each sample and used to determine median prediction error (MDPE) and median absolute prediction error (MDAPE) per patient. Risk factors for APE >30% were assessed using multivariable analysis. Results are presented as medians with inter-quartile ranges. ResultsFifty-eight patients with 283 blood samples (110 during CPB) were included. In the pre-CPB period, MDPE and MDAPE were –17.3 [–32.9 to 2.3] and 24.6 [12–37.7]%, whereas during CPB, they were –1.8 [–15.6 to 11.1] and 14.0 [6.74–27.1]%, respectively. There was no statistically significant difference between measured and predicted remifentanil plasma concentrations during CPB. Age, preoperative albumin concentrations, temperature, and haemodilution were not independently associated with MDAPE >30%. ConclusionsThe Minto model accurately predicts plasma remifentanil concentrations during cardiac surgery with CPB. Clinical trial registration2017-A03153-50.

Opioid Sensitivity in Children with and without Obstructive Sleep Apnea.

Opioids are a mainstay of perioperative analgesia. Opioid use in children with obstructive sleep apnea is challenging because of assumptions for increased opioid sensitivity and assumed risk for opioid-induced respiratory depression compared to children without obstructive sleep apnea. These assumptions have not been rigorously tested. This investigation tested the hypothesis that children with obstructive sleep apnea have an increased pharmacodynamic sensitivity to the miotic and respiratory depressant effects of the prototypic μ-opioid agonist remifentanil. Children (8 to 14 yr) with or without obstructive sleep apnea were administered a 15-min, fixed-rate remifentanil infusion (0.05, 0.1, or 0.15 μg · kg · min). Each dose group had five patients with and five without obstructive sleep apnea. Plasma remifentanil concentrations were measured by tandem liquid chromatography mass spectrometry. Remifentanil effects were measured via miosis, respiratory rate, and end-expired carbon dioxide. Remifentanil pharmacodynamics (miosis vs. plasma concentration) were compared in children with or without obstructive sleep apnea. Remifentanil administration resulted in miosis in both non-obstructive sleep apnea and obstructive sleep apnea patients. No differences in the relationship between remifentanil concentration and miosis were seen between the two groups at any of the doses administered. The administered dose of remifentanil did not affect respiratory rate or end-expired carbon dioxide in either group. No differences in the remifentanil concentration-miosis relation were seen in children with or without obstructive sleep apnea. The dose and duration of remifentanil administered did not alter ventilatory parameters in either group.

Propofol in combination with remifentanil for cesarean section: Placental transfer and effect on mothers and newborns at different induction to delivery intervals

ObjectiveThis study aims to describe the administration of propofol in combination with remifentanil for the induction of general anesthesia during cesarean section (CS). Our aim was to evaluate its impact on the drug concentrations of the maternal and neonatal blood at different induction of anesthesia to delivery (I–D) intervals as well as its effect on newborns. Materials and methodsIn this double-blind randomized controlled study, patients undergoing elective CS were administered anesthesia at short (n = 20) or long (n = 20) I–D intervals. Anesthesia was induced with 1 mg/kg propofol and 1 μg/kg remifentanil and maintained by continuous infusion of 3 mg/kg/h propofol and 7 μg/kg/h remifentanil. ResultsThe mean plasma propofol concentrations at delivery in the maternal arterial (MA) blood and the fetal umbilical arterial (UA) and venous (UV) blood in the short I–D interval group were 1.91, 1.17, and 0.51 μg/mL, respectively, while those in the long I–D interval group were 1.57, 1.07, and 0.61 μg/mL, respectively. The mean plasma remifentanil concentrations at delivery in the MA, UA, and UV in the short I–D interval group were 2.25, 1.43, and 0.65 ng/mL, respectively, and those in the long I–D interval group were 1.96, 1.25, and 0.75 ng/mL, respectively. There were no statistically significant differences in the neonatal Apgar scores and neurological adaptive capacity scores between the two groups. ConclusionsIt is safe to administer propofol in combination with remifentanil by continuous infusion after the bolus dose for the induction of anesthesia during cesarean section. Prolonging the I–D interval within a certain limit will not have any significant influence on the fetus.

Effects of different remifentanil target concentrations on MAC BAR of sevoflurane in gynaecological patients with CO2 pneumoperitoneum stimulus

To investigate the effects of different target plasma remifentanil concentrations on the minimum alveolar concentration of sevoflurane (MAC) for blocking adrenergic response (BAR) during laparoscopic gynaecological surgery with carbon dioxide insufflation. Seventy-five gynaecological patients with ASA I-II undergoing laparoscopic surgery were randomly assigned to three groups. Anaesthesia was induced by sevoflurane, and 0.1 mg kg(-1) of vecuronium i.v. was injected to facilitate tracheal intubation. After intubation the target plasma concentrations of remifentanil in Groups 1, 2, and 3 were adjusted to 0, 1, and 2 ng ml(-1), respectively. The changes in haemodynamics were observed before and after the creation of carbon dioxide pneumoperitoneum. The MAC BAR of sevoflurane in each group was determined by using an up-and-down sequential-allocation technique, and blood samples were collected at corresponding time points to determine the concentrations of remifentanil, norepinephrine, and epinephrine. In Groups 1, 2 and 3, the MAC BAR of sevoflurane was 4.6% (CI 95%: 4.3-4.9%), 2.4% (CI 95%: 2.2-2.6%), and 1.7% (CI 95%: 1.4-2.1%), respectively. No significant differences were found in the increase of norepinephrine, epinephrine, and mean arterial pressure after compared with before insufflation of pneumoperitoneum among the three groups. Remifentanil can effectively decrease the sevoflurane concentration to block sympathetic adrenergic response to CO2 pneumoperitoneum stimulus. At similar MAC BAR the haemodynamic and adrenergic response is not affected by the infused remifentanil concentration. The number of this clinical trial registry is ChiCTR-TRC-13004005, and the Universal Trial Number is U1111-1151-5630.

Influence of cardiac output on the pseudo‐steady state remifentanil and propofol concentrations in swine

The propofol concentration during constant infusion is affected by a change in cardiac output, but the effect of this change on remifentanil, which is frequently used in combination with propofol, is unclear. Ten swine were anaesthetised through inhalation of isoflurane and maintained with 1.5% isoflurane. After infusion of remifentanil (0.5 μg/kg/min) and propofol (6 mg/kg/h after 2 mg/kg bolus infusion) for 60 min (baseline 1), cardiac output was increased by continuous infusion of dobutamine and termination of isoflurane (high cardiac output state). Dobutamine infusion was then stopped, 1.5% isoflurane was restarted, and cardiac output was allowed to return to baseline (baseline 2). Finally, cardiac output was decreased by administration of 3% isoflurane (low cardiac output state). Blood samples were collected from the femoral artery at 10, 30, and 60 min after the change to each haemodynamic state. An inverse relationship was found between cardiac output and the plasma remifentanil and propofol concentrations. The plasma drug concentrations were given by the following equations: [remifentanil] (ng/ml) = 17.5/cardiac output (l/min) + 4.52; and [propofol] (μg/ml) = 3.34/cardiac output + 1.17. The influence of changes in cardiac output on remifentanil were similar to those for coadministered propofol and the influence on the concentration of each drug was greater with decreasing cardiac output. The plasma remifentanil concentration is influenced by cardiac output in a similar manner to that of propofol during remifentanil and propofol anaesthesia, although the metabolic sites are different.

Aspiration of a sponge during conscious sedation

Conscious sedation under monitored anesthesia care is used for a wide range of operations including dacryocystorhinostomy. The most common side effects are this respiratory depression and apnea [1], which require constant care from anesthesiologists. Recently, we experienced an uncommon case of aspiration of a small surgical sponge from the nasal cavity during dacryocystorhinostomy performed on the patient under conscious sedation using the total intravenous anesthesia (TIVA) technique. This is a rare but potentially serious complication [2]. Anesthesiologists need to be cautious about maintaining adequate sedation levels to prevent adverse events from occurring. Additionally, surgeons need to ensure that surgical materials are not unintentionally misplaced or lost. A 68-year-old woman was admitted for surgery to treat a nasolacrimal duct obstruction. After the patient arrived at the operating room, we initiated standard monitoring with bispectral index (BIS). For oxygen supplementation, a nasal cannula was placed between the lips of the patient with O2 3 L/min. After confirming that all monitored parameters were normal, we infused 1000 mg propofol (Fresopol MCT inj 2% Ⓡ , Fresenius Kabi, Graz, Austria) and remifentanil (ULTIVA Ⓡ , GlaxoSmithKline, Brentford, Middlesex, UK) using an Orchestra TM module (Fresenius Vial, Brezins, France). By regulating the plasma remifentanil concentration to 2.0 ng/ml, the BIS value of the patient fell to 85. Next, we set the target concentration of propofol at 1.5 mcg/ml and her BIS values were maintained at approximately 80. Under these conditions, the patient breathed spontaneously and responded to our orders. The surgeon started the operation and we maintained a stable anesthetic depth. After 30 minutes, the patient intermittently stopped breath ing, but responded when we attempted to reawaken her. Her BIS value was not changed between 80 to 85 in this period. We reduced the target concentration of propofol to 1.0 mcg/ml and remifentanilto 0.5 ng/ml, but the patient continued to snore and took a deep breath in response to our order. About 45 minutes later, she suddenly became apneic and failed to respond to our stimuli. Her oxygen saturation decreased from 96 to 90%. Even though we raised the patient’s chin, her saturation decreased to 75% momently after one deep breath with BIS value also fell to 60. We stopped the operation, and started mask ventilation with 100% O2. Her saturation increased rapidly to 95% and the BIS value returned to 80. After consulting with the surgeon about continuing the operation, we intubated the patient without administering a muscle relaxant. The patient was still unresponsive despite hav ing a BIS value of 80. Surgeons went on operation and finished without special event. The patient fully awoke near the end of operation, she couldn’t stand intubation. Therfore, we extubated unwillingly. After then, we noticed that a small sponge (Petipad TM Neurosurgical Sponges Pollak Int., Euroband, France) was missing. It had been packed into a deep nasal cavity to control bleeding but could not find it in the nasal or oral cavity. We suspected that the sponge had been swallowed rather than aspirated because the patient’s vital signs remained stable with 100% oxygen saturation. We examined the chest X-ray to determine the location of the gauze. We discovered that the radio-opaque thread dangling from the sponge was located in the midline of the chest (Fig. 1A). It followed the shape of the trachea and main bronchus. Since we had already extubated the trachea, we decided to re

Influence of haemorrhage on the pseudo-steady-state remifentanil concentration in a swine model: a comparison with propofol and the effect of haemorrhagic shock stage

The increase in remifentanil concentration during haemorrhagic shock and the difference between this effect and that for propofol are not fully understood. We investigated the influence of haemorrhage on the pseudo-steady-state remifentanil concentration in a porcine model and compared the changes with those for propofol. After infusion of remifentanil (0.5 µg kg⁻¹ min⁻¹) and propofol (6 mg kg⁻¹ h⁻¹ after 2 mg kg⁻¹ bolus infusion) for 60 min, nine swine [mean (standard deviation) body weight=26.3 (1.3) kg] were studied using a stepwise haemorrhage model (10% of estimated blood volume removed every 30 min until 1.5 h, and stepwise removal of 5% every 30 min thereafter until circulatory collapse). Haemodynamic and metabolic variables and plasma remifentanil and propofol concentrations were measured at every step. A mean volume of 913 (82) ml of blood was drained before reaching circulatory collapse. The increases in plasma concentrations from the prehaemorrhagic value fitted the following equations: % increase in remifentanil=2.1 × cumulative blood loss (% of initial blood volume) and % increase in propofol = 0.7 × cumulative blood loss during compensated shock; and % increase in remifentanil = 27.4 × cumulative blood loss-897 and % increase in propofol = 9.5 × cumulative blood loss-306 during uncompensated shock. Remifentanil concentrations were highly correlated with the reciprocal of cardiac output. During haemorrhage, the plasma remifentanil concentration showed a three-fold greater increase than that of propofol in administration by continuous infusion.

Effects of different target remifentanil concentrations on MACBAR of sevoflurane and catecholamineRAR in gynecological patients undergoing laparoscopic surgery

Objective To investigate the effects of different targeted plasma remifentanil concentrations on the minimum alveolar concentration of sevoflurane (MACBAR) and minimum plasma catecholamine concentration for blocking adrenergic response (CatecholamineBAR: NEBR, EBAR) in gynecological patients undergoing laparoscopic surgery using carbon dioxide pneumoperitoneum.Methods Seventy five gynecological patients undergoing laparoscopic surgery, ASA physical status Ⅰ -Ⅱ, were randomly assigned to three groups: control group (R0) and 2 remifentanil groups (R1, R2). Anesthesia was induced by target controlled infusion with remifentanil (plasma concentration 2 μg/L), and intravenous infection with 0.3 mg/kg etomidate. Vecuronium 0.1 mg/kg was administered to facilitate tracheal intubation. After intubation anesthesia was maintained with sevoflurane in all groups. But in R0, R1and R2, the targeted plasma concentration of remifentanil was adjusted to 0, 1 μg/L and 2 μg/L, respectively. The MACBAR of sevoflurane was determined by using a sequential design and pneumoperitoneum stimulation in each group, while blood samples were collected at corresponding time points to determinate catecholamine concentrations and the values of NEBAR, EBAR were calculated.Results In group R0, R1 and R2, the MACBARs of sevoflurane were (4.60±0.30)％, (2.37±0.21) ％ and(1.70±0.28) ％, respectively.No significant differences were found in NEBAR, EBAR and minimum MAP among the three groups. Conclusion The targeted plasma concentrations of remifentanil at 1 μg/L and 2 μg/L can significantly reduce MACBAR of sevoflurane by 48％ and 63％ respectively in gynecological patients undergoing laparoscopic surgery. However, the value of catecholamineBAR was not influenced by the changes of remifentanil's target plasma concentration and the end-tidal sevoflurane concentration. Key words: Sevoflurane; Remifentanil; MAC ; Adrenergic response; Catecholamine; Pneumoperitoneum

Placental transfer and neonatal effects of remifentanil as an adjuvant for cesarean section

Objective To investigate the placental transfer and neonatal effects of remifentanil as an adjuvant for cesarean section.Methods Forty ASA Ⅰ parturients at full term aged 26-32 yr weighing 70-90 kg undergoing elective cesarean section under combined spinal epidural anesthesia (CSEA) were randomly divided into 2 groups (n = 20 each): control group (C) and remifentanil group (R). The CSEA was performed at L3-4interspace and the upper spread of sensory block reached T6-8. Group R received TCI of remifentanil (target plasma concentration was set at 1.5 ng/ml) starting from performance of CSEA until blood samples were obtained. In group C equal volume of normal saline was infused instead of remifentanil. MAP, HR, RR, minute ventilation (MV), and OAA/S scores were recorded after the parturients had settled down for 5 min in the operating room (T0), at skin incision (T1), when the baby was being delivered (T2), uterus repaired (T3) and peritoneum closed (T4). Fetal heart rate (FHR) at T0 and immediately before skin disinfection, the duration between uterus incision and delivery of the baby (delivery time), body weight of the newborn, Apgar score at 1 min and 5 min after delivery and neonatal behavioral neurological assessment (NBNA) at 1 h and 24 h after delivery were also recorded.Adverse effects including hypotension, sinus bradycardia, raspiratory depression, muscle rigidity , nausea and vomiting were recorded. The middle segment of umbilical cord (about 10-15 cm long) was clamped at both ends with two clamps at delivery. Umbilical arterial (UA) and venous (UV) blood samples and maternal arterial (MA) blood samples were obtained within 3 min after delivery for blood gas analysis and determination of plasma remifentanil concentration using C,C-MS-SIM method. Results OAA/S scores were significantly lower at T1,2 in group R than in group C. There were no significant differences in MAP, HR, MY, RR, delivery time, FHR, blood gases, bedy weight of the newborn, Apgar scores and NBNA scores between the 2 groups. The plasma concentrations (C) of remifentanil were (0.85±0.31),(0.57±0.12) and (0.22±0.09) ng/ml respectively in maternal arterial, umbilical venous and arterial blood samples, CUV/CMA was 0.67±0.41 and CUA/CUV was 0.39±0.08. Conclusion Remifentanil given by TCI at a target plasma concentration of 1.5 ng/ml has no adverse effects on the newborn because of raid metabolism and redistribution of remlfentanil in the neonate after rapid placental transfer. Key words: Piperidines; Cesarean section; Infant, newborn; Placenta

Remifentanil versus remifentanil with paracervical block on plasma remifentanil concentrations and pulmonary function tests for transvaginal ultrasound-guided oocyte retrieval

The aim of this study is to compare plasma remifentanil concentrations and pulmonary function tests in subjects receiving remifentanil infusion (RI) versus RI with paracervical block (PCB) during transvaginal ultrasound-guided oocyte retrieval (TUGOR). Prospective, randomized. Assisted Conception Unit. Forty American Society ofAnesthesiologists I subjects requiring TUGOR. After ovarian hyperstimulation, subjects were randomly allocated into two groups to receive either RI (Group RI, n = 20) or RI with PCB (Group RI + PCB, n = 20). Heart rate (HR), mean arterial pressure (MAP), peripheral oxygen saturation (SpO2), end tidal carbon dioxide (ETCO2) tension, forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), and amount of remifentanil used were collected. Plasma remifentanil concentrations were calculated with STANPUMP software. HR, MAP, ETCO2, SpO2, FEV1, and FVC did not differ between the groups. Total amount of remifentanil used were 486 +/- 1.81 microg and 321 +/- 0.87 microg in groups RI and RI + PCB, respectively, (p < 0.05). In Group RI, plasma remifentanil concentrations were 4.7 ng mL(-1) and 4.2 ng mL(-1) during the second transvaginal puncture, and at the end of TUGOR, respectively, whereas corresponding plasma remifentanil concentrations were 3.1 ng mL(-1) and 2.6 ng mL(-1) in Group RI + PCB (p < 0.05). Both anesthesia regimens provided satisfactory analgesia without affecting FEV1 and FVC, but significantly higher plasma remifentanil concentrations were calculated when only RI was used as an anesthetic technique.