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AIM: Abundant data are available on the effect of the A118G (rs1799971) single-nucleotide polymorphism (SNP) of the µ-opioid receptor OPRM1 gene on morphine and fentanyl requirements for pain control. However, data on the effect of this SNP on intraoperative remifentanil requirements remain limited. We investigated the effect of this SNP on intraoperative remifentanil requirements. METHODS: We investigated 333 Japanese women, aged 21-69 years, who underwent laparoscopic gynecological surgery for benign gynecological disease under total intravenous anesthesia at Juntendo University Hospital. Average infusion rates of propofol and remifentanil during anesthesia and the average bispectral index (BIS) during surgery were recorded. Associations among genotypes of the A118G and phenotypes were examined with the Mann-Whitney U test. RESULTS: The average propofol infusion rate was not different between patients with different genotypes. The average remifentanil infusion rate was significantly higher in patients with the AG or GG genotype than the AA genotype (p = 0.028). The average intraoperative BIS was significantly higher in patients with the GG genotype than the AA or AG genotype (p = 0.039). CONCLUSIONS: The G allele of the A118G SNP was associated with higher intraoperative remifentanil requirements and higher intraoperative BIS values but was not associated with propofol requirements. Given that remifentanil and propofol act synergistically on the BIS, these results suggest that the G allele of the A118G SNP is associated with lower effects of remifentanil in achieving adequate intraoperative analgesia and in potentiating the sedative effect of propofol on the BIS.
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A 44-year-old woman with a subacute onset of an altered mental status, urinary retention, and fluctuating blood pressure was initially diagnosed with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, meeting the criteria of Graus et al. Cardiac arrest occurred, which required pacemaker placement. She subsequently showed profound flaccid limb paralysis, with magnetic resonance imaging demonstrating focal necrotic lesions localized in the anterior horn of the longitudinal segments of the spinal cord and in the pontine tegmentum. Enteroviruses or autoimmune encephalitis-associated autoantibodies were not detected. We herein report a case of acute flaccid myelitis with profound psychiatric symptoms and dysautonomia, resembling NMDAR encephalitis.
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Considerable individual differences are widely observed in the incidence of postoperative nausea and vomiting (PONV). We conducted a genome-wide association study (GWAS) to identify potential candidate single-nucleotide polymorphisms (SNPs) that contribute to PONV by utilizing whole-genome genotyping arrays with more than 950,000 markers. The subjects were 806 patients who provided written informed consent and underwent elective surgery under general anesthesia with propofol or desflurane. The GWAS showed that two SNPs, rs2776262 and rs140703637, in the LOC100506403 and CNTN5 gene regions, respectively, were significantly associated with the frequency of nausea. In another GWAS conducted only on patients who received propofol, rs7212072 and rs12444143 SNPs in the SHISA6 and RBFOX1 gene regions, respectively, were significantly associated with the frequency of nausea as well as the rs2776262 SNP, and the rs45574836 and rs1752136 SNPs in the ATP8B3 and LOC105370198 gene regions, respectively, were significantly associated with vomiting. Among these SNPs, clinical and SNP data were available for the rs45574836 SNP in independent subjects who underwent laparoscopic gynecological surgery, and the association was replicated in these subjects. These results indicate that these SNPs could serve as markers that predict the vulnerability to PONV. Our findings may provide valuable information for achieving satisfactory prophylactic treatment for PONV.
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BACKGROUND: Neuraxial anesthesia is widely used as the most effective and standard method in obstetric anesthesia. However, there is a concern that neuraxial anesthesia may be technically difficult or ineffective in pregnant women with spinal disease. Therefore, this study aimed to investigate the implementation rate of neuraxial anesthesia among pregnant women with spinal diseases and their success rate at our institution. METHODS: The subjects of this study were pregnant patients who delivered at Juntendo University Nerima Hospital between April 2017 and December 2020. After obtaining ethics committee approval, data were collected from patients' medical records. RESULTS: Of the 2682 pregnant women who delivered, 1550 underwent preanesthetic evaluation. There were 42 deliveries in 39 pregnant women with spinal diseases (1.7% of all pregnant women and 2.7% of those who underwent preanesthetic evaluation). The diagnoses included adolescent idiopathic scoliosis (51.3%), lumbar disc herniation (23.1%), and others. The mode of delivery was the elective cesarean section in 5 cases, emergent cesarean section in 8 cases, and vaginal delivery in 29 cases. Only one case required general anesthesia. Of the 38 cases of labor analgesia, the neuraxial block was inadequate in 3 cases (7.9%) and technically difficult in 3 cases (7.9%). However, the patients complained of no lower extremity neuropathy, infection, or inadvertent dural puncture. DISCUSSION: Neuraxial anesthesia was an option in most cases, even in pregnant women complicated with spinal disease, if an anesthesiologist's plan before delivery after careful preanesthetic evaluation.
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BACKGROUND: Abnormal cardiotocogram (CTG) tracing may appear after induction of neuraxial labor analgesia. Non-reassuring fetal status (NRFS) indicated by severely abnormal tracings, such as prolonged deceleration (PD) or bradycardia, can necessitate immediate operative delivery. Combined spinal epidural analgesia (CSEA) is known to result in more frequent abnormal tracings than epidural analgesia (EA); however, the corresponding data related to dural puncture epidural (DPE) are unclear. We aimed to evaluate the rates of incidence of severe abnormal CTG after induction of DPE and CSEA. METHODS: In this study of nulliparous women with full-term pregnancy, data for the DPE intervention group were prospectively collected, while those for the CSEA control group were obtained from medical records. Neuraxial analgesia was performed with cervical dilation ≤ 5 cm, administering initial epidural dosing of 15 mL of 0.125% levobupivacaine with fentanyl 2.5µg/mL for DPE, and intrathecal 0.5% bupivacaine 2.5 mg (0.5ml), fentanyl 10 µg (0.2ml), and 1.3 mL of saline for CSEA. The primary outcome was the incidence of PD, defined as a fetal heart rate reduction ≥ 15 bpm below the baseline and with a lowest value < 80 bpm, and lasting for ≥ 2 min but < 10 min (fetal heart rate < 80 bpm does not have to last for ≥ 2 min), within 90 min after induction of neuraxial labor analgesia. RESULTS: A total of 302 patients were analyzed, with 151 in each group. The incidence of PD after DPE induction was significantly lower than that after CSEA induction (4.0% vs. 14.6%, P = 0.0015, odds ratio = 0.243, 95% confidence interval = 0.095-0.617). CONCLUSION: DPE appears to be a safer method compared to CSEA for neuraxial labor analgesia in the early stages of labor for nulliparous women. TRIAL REGISTRATION: UMIN-CTR: UMIN000035153 . Date registered: 01/01/2019.
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Analgesia Epidural , Analgesia Obstétrica , Embarazo , Humanos , Femenino , Proyectos Piloto , Frecuencia Cardíaca Fetal , Incidencia , Desaceleración , Analgesia Obstétrica/efectos adversos , Analgesia Obstétrica/métodos , Punción Espinal/métodos , Analgésicos , Fentanilo , Analgesia Epidural/efectos adversos , Analgesia Epidural/métodos , Trabajo de Parto InducidoRESUMEN
Timely fibrinogen replacement is key to treating critical hemorrhage. Measuring fibrinogen concentration by conventional laboratory tests requires centrifugation of blood samples and is often time-consuming. A point-of-care testing device (A&T, Yokohama, Japan), CG02N, has been available in Japan since 2011 to measure fibrinogen concentration without centrifugation. However, it has not been widely used as it requires dilution of blood samples using manual micropipetting. To further speed up and simplify the fibrinogen measurement, an improved device called FibCare (Atom Medical, Tokyo, Japan) was developed to avoid diluting blood samples. The purpose of this study is to verify the reliability of FibCare against laboratory measurement using the Clauss method. Fibrinogen concentrations with 60 sodium citrated whole blood samples were measured by both FibCare and Clauss methods in the laboratory. Measured values with the Clauss method were distributed in the 88-300 mg/dL range. By comparing these results, a significant positive correlation was observed between the FibCare and Clauss method (Y = 12.402 + 0.982 X; R = 0.891; P < 0.01). The study indicated that FibCare allows accurate measurement of fibrinogen concentration and shows a possibility to contribute to optimal fibrinogen replacement therapy during critical hemorrhage.
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Fibrinógeno , Sistemas de Atención de Punto , Pruebas de Coagulación Sanguínea , Hemorragia , Humanos , Reproducibilidad de los ResultadosRESUMEN
AIM: This study aimed to examine the association between clinically diagnosed chorioamnionitis and failed conversion of epidural labor analgesia to cesarean delivery anesthesia. METHODS: This retrospective, single-center cohort study, conducted in a university hospital, enrolled term parturients undergoing emergency cesarean section after induction of epidural labor analgesia between September 2015 and May 2019. For the purpose of this study, all cases were re-examined to ensure that they fulfilled the criteria of chorioamnionitis, regardless of the actual indication for cesarean section proposed by obstetricians at the time of application. The primary outcome was failure of conversion of epidural labor analgesia to cesarean delivery anesthesia. Multivariable logistic regression analysis was performed to investigate the association between chorioamnionitis and failure of anesthesia for cesarean section. RESULTS: Among the 180 parturients reviewed, 58 (43.9%) fulfilled the criteria for chorioamnionitis. Failure of epidural conversion in the chorioamnionitis (+) group was significantly higher than in the chorioamnionitis (-) group (46.6% [27/58] vs. 18.9% [14/74], crude odds ratio = 3.7, 95% confidence interval: 1.7-8.3). After adjustment for potential confounders (age, body mass index, multiparity, and duration for epidural labor analgesia), chorioamnionitis was found to be associated with failure of anesthesia for cesarean sections (adjusted odds ratio = 3.6, 95% confidence interval: 1.6-8.4). CONCLUSIONS: Chorioamnionitis is associated with the failed conversion of epidural labor analgesia to cesarean delivery anesthesia.
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Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Anestesia Obstétrica/métodos , Cesárea/métodos , Corioamnionitis/fisiopatología , Trabajo de Parto/fisiología , Adulto , Femenino , Humanos , Embarazo , Estudios RetrospectivosRESUMEN
BACKGROUND: We report a case in which a list of high-risk pregnant women on cloud-based business communication tools was useful in formulating an anesthetic plan for unscheduled cesarean section. CASE PRESENTATION: A 37-year-old woman, who had been prescribed icosapentate for hypertriglyceridemia, received an antenatal anesthetic evaluation for possible cesarean delivery, and it was agreed that the anesthetic method for emergency cesarean section was general anesthesia if the surgery would take place within 7 days after the discontinuation of the drug, and regional anesthesia if it would take place any time later. Then this agreement was uploaded on the cloud-based business communication tools, and updated until she delivered her baby via unscheduled cesarean section. CONCLUSIONS: A cloud-based business communication tools was useful in formulating an anesthesia plan for a patient undergoing a cesarean delivery. However, more discussion would be needed to utilize it in security.
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BACKGROUND: Fibrinogen concentration is an important indicator of the treatment for obstetric disseminated intravascular coagulation (DIC). We present how using the fibrinogen measuring device could solve problems in the treatment of postpartum hemorrhage with complicated DIC. CASE PRESENTATION: A 32-year-old woman with monochorionic diamniotic twins at 22 weeks of pregnancy was diagnosed with placental abruption and underwent emergent cesarean section. The estimated blood loss was 8375 g. She was transferred to our hospital for further treatment. Compressive uterine sutures and balloon tamponade were performed. We transfused fibrinogen and fresh frozen plasma actively during the operation to maintain plasma fibrinogen above 200 mg/dL by using a point-of-care fibrinogen measuring device. In spite of massive hemorrhage exceeding 10 L, she was extubated at the end of the operation and discharged on the 7th day after the operation. CONCLUSION: The portable fibrinogen measuring device was useful for point-of-care assessment of obstetric DIC.
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BACKGROUND: Opioids are widely used as effective analgesics, but opioid sensitivity varies widely among individuals. The underlying genetic and nongenetic factors are not fully understood. Based on the results of our previous genome-wide association study, we investigated the effects of single nucleotide polymorphisms (SNPs) of the astrotactin 2 (ASTN2) gene on pain-related phenotypes in surgical patients. METHODS: We investigated the effects of two SNPs, rs958804 T/C and rs7858836 C/T, of the ASTN2 gene on eight and seven pain-related phenotypes in 350 patients who underwent laparoscopic colectomy (LAC) and 358 patients who underwent mandibular sagittal split ramus osteotomy (SSRO), respectively. In both surgical groups, intravenous fentanyl patient-controlled analgesia (PCA) was used for postoperative analgesia, and 24-hour postoperative PCA fentanyl use was the primary endpoint. RESULTS: The association analyses among the two SNPs and pain-related traits showed that 24-hour fentanyl use was significantly associated with the two SNP genotypes in both surgical groups. The Mann-Whitney test showed that 24-hour fentanyl use was lower in patients with the C allele than in patients with the TT genotype of the rs958804 T/C SNP (P = .0019 and .0200 in LAC and SSRO patients, respectively), and it was lower in patients with the T allele than in patients with the CC genotype of the rs7858836 C/T SNP (P = .0017 and .0098 in LAC and SSRO patients, respectively). CONCLUSION: The two SNPs of the ASTN2 gene were consistently associated with fentanyl requirements after two different types of surgery. These findings may contribute to personalized pain control.
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Analgesia Controlada por el Paciente , Analgésicos Opioides/administración & dosificación , Colectomía , Fentanilo/administración & dosificación , Glicoproteínas/genética , Laparoscopía , Osteotomía Mandibular , Proteínas del Tejido Nervioso/genética , Osteotomía Sagital de Rama Mandibular , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/genética , Anciano , Colectomía/efectos adversos , Femenino , Humanos , Laparoscopía/efectos adversos , Masculino , Osteotomía Mandibular/efectos adversos , Persona de Mediana Edad , Osteotomía Sagital de Rama Mandibular/efectos adversos , Fenotipo , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Neuraxial labor analgesia is known to increase the rate of instrumental delivery and prolong the second stage of labor; however, there is no standard method to evaluate the progress of labor under analgesia. Friedman curve is considered the gold standard for evaluating the progress of labor. However, it included not only neuraxial labor analgesia but also labor without analgesia. Thus we compared the labor curves of primiparous women undergoing labor with and without neuraxial labor analgesia, to understand the progress of labor in both groups and to arrive at a standard curve to monitor the progress of labor under neuraxial analgesia. METHODS: Primiparous women with cephalic singleton pregnancies who delivered at term from 2016 to 2017 were included. Two hundred patients who opted for combined spinal-epidural (CSE) labor analgesia were included in the CSE group and 200 patients who did not undergo CSE were included in the non-CSE group. In all, 400 cases were examined retrospectively. The evaluation parameters were cervical dilation and fetal station, and we calculated the average value per hour to plot the labor curves. RESULTS: The labor curve of the non-CSE group was significantly different from the Friedman curve. In the CSE group, the time from 4 cm dilation of the cervix to full dilation was 15 h; in addition, the speed of cervical dilation was different from that in the non-CSE group. The progress of labor in the CSE group was faster than that in the non-CSE group during the latent phase; however, the progress in the CSE group was slower than that in the non-CSE group during the active phase. CONCLUSIONS: Neuraxial labor analgesia results in early cervical dilation and descent of the fetal head; thus, appropriate advance planning to manage the delivery may be essential.
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Analgesia Epidural , Analgesia Obstétrica/métodos , Trabajo de Parto/fisiología , Adulto , Anestesia Raquidea , Femenino , Humanos , Paridad , Embarazo , Estudios RetrospectivosRESUMEN
AIM: This study aimed to investigate the rate of labor-onset hypertension (LOH) under neuraxial labor analgesia and the effect of neuraxial labor analgesia on LOH. METHODS: A retrospective study was conducted in a tertiary university hospital from 2015 to 2016. Patients who were admitted to the hospital for vaginal delivery under combined spinal and epidural anesthesia were selected. LOH was defined as the elevation of systolic blood pressure (BP) to ≥140 mmHg or diastolic BP to ≥90 mmHg for the first time after the onset of labor. Cases of LOH that persisted after neuraxial labor analgesia (prolonged LOH) were further analyzed to determine the hypertension severity and therapeutic intervention rate. RESULTS: Among 775 patients, 213 (28.4%) developed LOH. Prolonged LOH was observed in 30 patients (3.9%). LOH severity and the likelihood of prolonged LOH were positively correlated. Therapeutic intervention was administered only to the patients with prolonged LOH, that is, to 100% of those with emergent hypertension, to 21.1% of those with severe hypertension during labor, and to 36.8% of those with severe hypertension, to 55.6% of those with mild hypertension in the post-partum period. CONCLUSION: The rate of LOH was reduced significantly after neuraxial labor analgesia. Patients with prolonged LOH should be carefully followed up during labor and in the post-partum period because such patients often require antihypertensive therapy.
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Analgesia Epidural/efectos adversos , Analgesia Obstétrica/efectos adversos , Presión Sanguínea/efectos de los fármacos , Hipertensión/inducido químicamente , Complicaciones del Trabajo de Parto/inducido químicamente , Adulto , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Trabajo de Parto/fisiología , Complicaciones del Trabajo de Parto/epidemiología , Complicaciones del Trabajo de Parto/fisiopatología , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The coexistence of distinct neurodegenerative diseases in single cases has recently attracted greater attention. The phenotypic co-occurrence of progressive supranuclear palsy (PSP) and amyotrophic lateral sclerosis (ALS) has been documented in several cases. That said, the clinicopathological comorbidity of these two diseases has not been demonstrated. CASE PRESENTATION: A 77-year-old man presented with gait disturbance for 2 years, consistent with PSP with progressive gait freezing. At 79 years old, he developed muscle weakness compatible with ALS. The disease duration was 5 years after the onset of PSP and 5 months after the onset of ALS. Neuropathological findings demonstrated the coexistence of PSP and ALS. Immunohistochemical examination confirmed 4-repeat tauopathy, including globose-type neurofibrillary tangles, tufted astrocytes, and oligodendroglial coiled bodies as well as TAR DNA-binding protein 43 kDa pathology in association with upper and lower motor neuron degeneration. Immunoblotting showed hyperphosphorylated full-length 4-repeat tau bands (64 and 68 kDa) and C-terminal fragments (33 kDa), supporting the diagnosis of PSP and excluding other parkinsonian disorders, such as corticobasal degeneration. Genetic studies showed no abnormalities in genes currently known to be related to ALS or PSP. CONCLUSIONS: Our case demonstrates the clinicopathological comorbidity of PSP and ALS in a sporadic patient. The possibility of multiple proteinopathies should be considered when distinct symptoms develop during the disease course.
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Esclerosis Amiotrófica Lateral/complicaciones , Encéfalo/patología , Parálisis Supranuclear Progresiva/complicaciones , Anciano , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/patología , Astrocitos/patología , Encéfalo/diagnóstico por imagen , Comorbilidad , Proteínas de Unión al ADN , Resultado Fatal , Humanos , Masculino , Trastornos del Movimiento/etiología , Ovillos Neurofibrilares/patología , Parálisis Supranuclear Progresiva/diagnóstico por imagen , Parálisis Supranuclear Progresiva/patología , Proteínas tau/análisisRESUMEN
A previous study reported that a massive cerebral infarct in the territory of the middle cerebral artery (MCA) may be associated with development of neurofibrillary tangles (NFTs) in the ipsilateral basal nucleus of Meynert (BNM). We analyzed 19 cases of an MCA territory infarct and 12 with a putaminal hemorrhage (mean age 82.5 years; female/male ratio 8/23; mean time from stroke onset to autopsy 4182 days). In both groups, 74-100% had a significantly higher rate of phosphorylated tau immunoreactive or Gallyas Braak silver stain-positive neurons on the BNM-affected side than on the BNM-unaffected side. These NFTs were immunoreactive for anti-RD3 and anti-RD4 antibodies, and a triple-band pattern was observed by immunoblot analysis with anti-tau antibody. Most NFTs might be formed within the 5-10 years after stroke onset. There were significantly more TAR DNA-binding protein 43 (TDP43) immunoreactive structures on the BNM-affected side than on the BNM-unaffected side. We showed that many NFTs with TDP43-immunoreactive structures were observed in the ipsilateral BNM associated with a massive cerebral infarct in the MCA territory or a putaminal hemorrhage.
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Núcleo Basal de Meynert/metabolismo , Hemorragia Cerebral/metabolismo , Infarto Cerebral/metabolismo , Proteínas de Unión al ADN/metabolismo , Ovillos Neurofibrilares/metabolismo , Proteínas tau/metabolismo , Anciano , Anciano de 80 o más Años , Núcleo Basal de Meynert/química , Núcleo Basal de Meynert/patología , Hemorragia Cerebral/patología , Infarto Cerebral/patología , Proteínas de Unión al ADN/análisis , Femenino , Humanos , Masculino , Ovillos Neurofibrilares/química , Ovillos Neurofibrilares/patología , Proteínas tau/análisisAsunto(s)
Catatonia/complicaciones , Catatonia/terapia , Terapia Electroconvulsiva/métodos , Trastornos Psicóticos/complicaciones , Trastornos Psicóticos/terapia , Catatonia/etiología , Femenino , Humanos , Persona de Mediana Edad , Rigidez Muscular/terapia , Trastornos Psicóticos/etiología , Resultado del TratamientoAsunto(s)
Anestesia Obstétrica , Anestesia Raquidea , Cesárea , Femenino , Feto , Humanos , Norepinefrina , Ondansetrón , Embarazo , VasoconstrictoresRESUMEN
At 37 years of age, the patient initially presented with symptoms of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) during her 1st pregnancy. She was treated with intravenous immunoglobulin (IVIg), and showed favorable recovery, becoming almost asymptomatic by the age of 38. At 39 years of age, during her puerperal period of her second pregnancy, she developed symmetrical muscle weakness and sensory disturbance of the upper and lower limbs. Nerve conduction studies revealed diffuse demyelination of peripheral nerves, and she was diagnosed with recurrence of CIDP. Once again, she showed remarkable improvement after IVIg therapy, and she has remained asymptomatic without the induction of preventative therapies. Recurrence of CIDP triggered in accordance with multiple pregnancies is extremely rare, and its clinical and electrophysiological features are presented in this report.
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Inmunoglobulinas Intravenosas/administración & dosificación , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/terapia , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/terapia , Adulto , Técnicas de Diagnóstico Neurológico , Femenino , Humanos , Conducción Nerviosa , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/fisiopatología , Embarazo , Recurrencia , Riesgo , Resultado del TratamientoRESUMEN
The importance of fibrinogen replacement therapy in obstetric disseminated intravascular coagulation is well recognized. However, fibrinogen measurement in conventional laboratories has been a time-consuming task. Recently, a Japanese manufacturer developed a portable device that enables immediate fibrinogen measurement at the point of care. This report describes a case in which this device was used for the successful management of obstetric disseminated intravascular coagulation.
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Coagulación Intravascular Diseminada/terapia , Fibrinógeno/administración & dosificación , Fibrinógeno/análisis , Hemorragia Posparto/terapia , Adulto , Femenino , HumanosRESUMEN
PURPOSE: Maternal remifentanil infusion is used for minimally invasive fetal surgery or ex-utero intrapartum treatment. The fetal-to-maternal (F/M) ratio of remifentanil concentration at various dosing regimens is useful to manage remifentanil effects. The aim of this study was to investigate the F/M ratio of remifentanil at various concentrations. METHODS: Five pregnant ewes received continuous remifentanil infusion under propofol anesthesia. The remifentanil infusion rate was increased by 0.4 µg/kg/min every 15 min. The response to tail clamping in fetuses was assessed immediately before the change of infusion rate. Arterial remifentanil concentrations in the mother and fetus were determined at each tail clamp. After observing a loss of response to tail clamping, remifentanil infusion was terminated and the concentrations were assessed. RESULTS: The median remifentanil maximum infusion rate and maternal concentration were 3.0 µg/kg/min (range 2.4-3.6) and 21.6 (range 18.0-29.9) ng/mL, respectively. During continuous infusion, the F/M ratio was 0.15 (0.07-0.17), and the slope of the linear regression for the F/M ratio versus infusion rate in each individual was -0.001 ± 0.012/µg kg min (P = 0.876 vs hypothetical value of 0). The F/M ratio at the first sampling point in the elimination phase [0.33 (0.07-0.65)] was higher (P = 0.033) than at the last sampling point during continuous infusion [0.15 (0.06-0.17)]. CONCLUSION: The F/M ratio was constant at a steady state regardless of the remifentanil concentration up to 29.9 ng/mL, and increased in the elimination phase in pregnant ewes.