Randomized double-blind comparison of the effects of intramyometrial and intravenous oxytocin during elective cesarean section.

AIM: Obstetricians sometimes administer intramyometrial oxytocin to stimulate uterine contraction during cesarean section, but its effects have not been well investigated. We performed a randomized, double-blind study to test the hypothesis that a small dose of intramyometrial oxytocin would induce acceptable uterine contractility more quickly and with fewer hemodynamic side-effects than the same dose administered intravenously. METHODS: Forty women with a single fetus at ≥36 weeks of gestational age scheduled for elective cesarean section under spinal anesthesia were randomized to the intravenous and intramyometrial groups to receive oxytocin at 0.07 IU/kg. The drug was administered immediately after umbilical cord clamping. Systolic blood pressure, heart rate, intraoperative blood loss, uterine tone, total amount of intraoperative oxytocin, and additional uterotonic drugs administered in the first 24 h were compared. RESULTS: Maximum uterine contractility was achieved after 2 and 10 min for the intravenous and intramyometrial groups, respectively. The mean hemodynamic parameters of the intramyometrial group were stable. In contrast, the intravenous group showed a reduction in systolic blood pressure after 2-4 min and increased heart rate after 1-2 min. Intraoperative blood loss, total oxytocin dose, and frequency of additional uterotonic drugs were comparable between the two groups. CONCLUSION: Although intraoperative blood loss was comparable, a small dose of intramyometrial oxytocin was inappropriate to obtain a prompt and acceptable uterine contraction during cesarean section.

[A Case of Rocuronium Anaphylaxis in which Anesthesia was Safely Performed after Selection of an Alternative Drug after a Skin Test].

We report our experience of a patient with a history of anaphylactic shock suspected to be caused by rocuronium who was scheduled to undergo hepatic tumor resection. The patient was a 17-year-old female (height : 166 cm, weight : 46 kg). During general anesthesia at another hospital several years ago, she had an anaphylactic shock, and rocuronium was suspected to be the offending drug. To collect information and search for the cause, skin tests were performed for rocuronium, vecuronium and suxamethonium. She was positive for rocuronium, and negative for other drugs. At anesthesia induction, we administered vecuronium and confirmed no development of anaphylaxis before commencement of surgery. In the perioperative period, she had no symptoms that indicated anaphylaxis. Since there is potential high cross-reactivity among muscle relaxants, it is important to perform a test for alternative drugs when a muscle relaxant may be a cause of anaphylaxis. Selection and administration of an alternative drug should be carefully performed, even when a skin test is negative for the alternative drug.

[Pressure Ulcer Caused by Long-term Keeping of the Same Body Position during Epidural Labour Analgesia].

We report the case of a 34-year-old woman (height: 153 cm, weight : 62.4 kg, non-pregnant weight : 52 kg, uniparous) without underlying diseases who developed pressure ulcer due to keeping a similar body position during long-term epidural delivery. Induction of childbirth was started in gestational week 40, causing reduction of fetal heart rate, which improved after adoption of a right lateral recumbent position. Severe contractions occurred and epidural labour analgesia was started. The fetal heart rate decreased again and induction of childbirth was suspended, but the right lateral recumbent position was maintained. Epidural administration was continued due to persistent contractions. Next morning, induction of childbirth was restarted and birth occurred in approximately 6 hours. The right lateral recumbent position was maintained for approximately 20 hours. At childbirth, a pressure ulcer was present in the intertrochanteric part of the right femur. The causes included insufficient knowledge of medical staff about the risk of pressure ulcer during epidural delivery, and no position change. A decreased sensation and blocked motor nerve caused by epidural anesthesia might have accelerated pressure ulcer development. This case suggests that preventive measures against pressure ulcer are required in epidural anesthesia in pregnant women.

[Anesthetic Management of Massive Postpartum Haemorrhage in Which Uterine Compression Sutures Were Used].

BACKGROUND: Uteline compression sutures which preserve portion of placenta tends to cause disseminated intravascular coagulation (DIC). But there have been no reports of anesthetic management of massive postpartum haemorrhage in which uterine compression sutures were used. METHODS: We reviewed the anesthetic management of 9 cases of massive postpartum haemorrhage in which uterine compression sutures were used in our hospital from May 2010 until Sep 2012. RESULTS: Seven cases were complicated by DIC (or the possibility of DIC) and required early infusion of blood products. Six cases required the use of ventilators. All cases recovered and were ultimately discharged. CONCLUSIONS: In the cases of massive postpartum haemorrhage in which uterine compression sutures were used, serious blood loss occurred during the operation, leading to a high probability of the development of DIC. Thus, it is necessary to manage DIC immediately.

[The McGRATH MAC Video Laryngoscope Facilitates Probe Insertion during Transesophageal Echocardiography].

BACKGROUND: A transesophageal echocardiography (TEE) probe is often inserted blindly. However, it is desirable to insert it under visual guidance because the blind technique sometimes causes difficulty and may contribute to serious, but rare, complications. This prospective study compared the usefulness of TEE insertion between a brand-new McGRATH MAC video laryngoscope (McGRATH) and a Macintosh laryngoscope (Macintosh). METHODS: We randomly assigned 80 adult patients undergoing cardiovascular surgery into two groups according to the laryngoscope used for TEE probe insertion: the McGRATH (McG Group; n = 40) and Macintosh (MC Group; n = 40) groups. End points included patient demographics, procedure duration, and resistance during insertion (grades 1-5). RESULTS: No differences were found in patient demographics between the groups. There was no significant difference in procedure duration between the groups (P = 0.116). Resistance during insertion was significantly lower in the McG Group than in the MC Group (P < 0.001). There were no failures of insertion in the McG Group. CONCLUSIONS: There were no failures of insertion in the McG Group. Resistance during insertion was lower with the McGRATH than Macintosh. The McGRATH was shown to be very useful when inserting TEE probes.

The Influence of Hypovolemia and Fluid Resuscitation During Hemorrhagic Shock on Apneic Oxygen Desaturation After Preoxygenation in a Swine Model.

BACKGROUND: Patients experiencing major bleeding often require both aggressive fluid resuscitation and rapid sequence tracheal intubation. The influence of hemorrhage-induced hypovolemia, and/or subsequent fluid resuscitation, on the time until critical oxygen desaturation is not well described. We studied the time to oxygen desaturation in a pig model of hemorrhage shock and colloid resuscitation. METHODS: After anesthetic induction with isoflurane, 9 swine (mean ± SD = 25.3 ± 0.6 kg) were studied with the use of a stepwise hemorrhage and fluid resuscitation model with 4 sequential stages: 600 mL hemorrhage, 600 mL hydroxyethyl starch infusion, a further 600 mL hemorrhage, and a second 600 mL hydroxyethyl starch infusion. At each stage, after 5 minutes of mechanical ventilation with 100% oxygen, we induced apnea and measured the time to oxygen desaturation (oxygen saturation [SpO2] <70%). Hemodynamic and blood gas variables were recorded, and the cerebral and peripheral tissue oxygenation indices were recorded by near-infrared spectroscopy. RESULTS: The times ± SD to SpO2 <70% at each stage were 136 ± 41 (baseline), 147 ± 41 (hemorrhage), 131 ± 38 (resuscitation), 147 ± 38 (repeat hemorrhage), and 134 ± 36 seconds (repeat resuscitation). The mean differences in times before and after hemorrhage were 11.2 (6.5 to 16.0, P = 0.0052) and 16.0 (11.0 to 21.0, P < 0.0001), respectively. PaO2 before and after apneic desaturation (at SpO2 < 70%) was not different between stages. On the basis of tissue oxygenation index findings, hypovolemia decreased oxygen consumption, and fluid resuscitation recovered this parameter. CONCLUSIONS: In patients with acute hemorrhagic shock, a hypovolemic state increases the duration of apnea until critical oxygen desaturation. Clinicians should thus consider the relationship between fluid resuscitation and time to desaturation when performing tracheal intubation in such patients.

Treatment of acute exacerbation of idiopathic pulmonary fibrosis with direct hemoperfusion using a polymyxin B-immobilized fiber column improves survival.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has an extremely poor prognosis and there is currently no effective treatment for this condition. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) improves oxygenation, but it is unclear whether treatment of AE-IPF with PMX-DHP affects survival. This study elucidated the effectiveness and safety of PMX-DHP for the treatment of AE-IPF. METHODS: This study included 31 patients with 41 episodes of AE-IPF. All patients received steroids. Of 31, 14 patients (20 episodes) were treated with PMX-DHP. The laboratory and physiological test results after the start of therapy and survival were retrospectively compared between patients treated with and without PMX-DHP. RESULTS: Patients treated with PMX-DHP had a significantly greater change in PaO2/FiO2 ratio (mean ± SEM, 58.2 ± 22.5 vs. 0.7 ± 13.3, p = 0.034) and a smaller change in white blood cell count (-630 ± 959 /µL vs. 4500 ± 1190 /µL, p = 0.002) after 2 days of treatment than patients treated without PMX-DHP. The 12-month survival rate was significantly higher in patients treated with PMX-DHP (48.2% vs. 5.9%, p = 0.041). PMX-DHP was effective in patients with more severe underlying disease (GAP stages II or III; 12-month survival rate 57.1% with PMX-DHP vs. 0% without PMX-DHP, p = 0.021). Treatment with PMX-DHP was an independent predictor of better prognosis (hazard ratio 0.345, p = 0.037). Mild pulmonary thromboembolism occurred in one patient treated with PMX-DHP. CONCLUSIONS: Treatment of AE-IPF with PMX-DHP is tolerable and improves 12-month survival.

Evaluation of near infrared spectroscopy for detecting the ß blocker-induced decrease in cerebral oxygenation during hemodilution in a swine model.

ß blockers reduce cerebral oxygenation after acute hemodilution and may contribute to the incidence of stroke when used perioperatively. The goal of the study was to investigate whether cerebral tissue oxygenation using near infrared spectroscopy can detect the ß blocker-induced decrease in cerebral oxygenation depending on the severity of hemodilution and/or the dose of ß blockers. Animals were anesthetized with 2% isoflurane and randomly assigned to a landiolol or esmolol group. After baseline measurement, landiolol or esmolol was administered at 40 µg/kg/min for 20 min, increased to 200 µg/kg/min for 20 min, and then stopped. Hemodynamic and arterial variables and the tissue oxygenation index (TOI) were recorded at each ß blocker dose. Two stages of hemodilution were sequentially induced by repeated hemorrhage of 600 ml (33% of estimated blood volume) and infusion of the same volume of hydroxyethylstarch. During each stage, landiolol or esmolol was similarly administered and measurements were made. Landiolol and esmolol both dose-dependently decreased heart rate, mean arterial pressure and cardiac output, depending on the severity of hemodilution. Landiolol at 40 µg/kg/min was almost equivalent in potency to 200 µg/kg/min esmolol for decreasing HR before hemodilution. Based on the TOI, short-acting ß blockers reduced cerebral oxygenation in a dose-dependent manner during hemodilution, and oxygenation returned to the baseline level after drug infusion was stopped. TOI may be useful for identification of a decrease in cerebral oxygenation for patients receiving ß blockade during surgery associated with major bleeding.

Radial artery cannulation decreases the distal arterial blood flow measured by power Doppler ultrasound.

Radial arterial cannulation is a popular technique for continuous hemodynamic monitoring in an area of anesthesia and intensive care. Although the risk for invasive monitoring is considerable, there is scarce information about the change in blood flow of cannulated vessel after the catheterization. In the current investigation, we evaluated the change in the cannulated arterial blood flow. Six volunteers (study 1) and eight post-surgical patients (study 2) were enrolled into the studies. In the study 1, the both side of diameter of radial artery (RA), ulnar artery (UA) and dorsal branch of radial artery (DBRA) of participants were measured using power Doppler ultrasound (PDU) with or without proximal oppression. In the study 2, the diameter of RA, UA and DBRA of the both intact and cannulated side were compared. Study 1: The diameter of RA was 3.4 (0.52) [mean (SD)] mm and the proximal oppression significantly decreased the diameter to 1.8 (0.59) mm. The diameter of DBRA measured by PDU also decreased 2.0 (0.60)-1.3 (0.59) mm. Study 2: There was no difference between the diameters of right and left RA, however, the UA was larger [3.4 (0.60) vs. 2.8 (0.83) mm] and the DBRA was narrower [1.4 (0.43) vs. 2.0 (0.47) mm] in the cannulated side. The diameters of DBRA were different between the intact and cannulated side in the patients. Although there is no information of relationships between cause of severe complication and decreased flow, significant reduction of blood flow should be concerned.

[Anesthetic Management of a Patient Complicated with Marfan Syndrome and Suffering from Stanford Type A Aortic Dissection during Pregnancy].

We report a case of a 36-year-old woman at 34 weeks of gestation complicated with Marfan syndrome who underwent Bentall type aortic replacement surgery due to Stanford type A aortic dissection after undergoing caesarean section. Since this patient exhibited severe hypotension before coming to the operating room, it was very difficult to determine whether the cardiac surgery or caesarean section should be performed first. In this case, the caesarean section was performed first, followed by Bentall's surgery. Although intra-aortic balloon pumping and percutaneous cardiopulmonary support were required after weaning from the cardiopulmonary bypass, she was discharged on post-operative day (POD) 40 and the baby was discharged on POD 60, without signs of cerebral palsy. Unfortunately, this patient died on POD 57, due to heart failure. We discuss how to determine the priority of surgeries for patients who require emergency surgery for cardiovascular disease during pregnancy.

Impact of CYP3A5*3 on plasma exposure and urinary excretion of fentanyl and norfentanyl in the early postsurgical period.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Dexmedetomidine-induced atrioventricular block followed by cardiac arrest during atrial pacing: a case report and review of the literature.

Sinus bradycardia is a well-known consequence of stimulation of presynaptic α2 adrenergic receptors due the adminstration of dexmedetomidine. One of the most serious adverse effects of dexmedetomidine is cardiac arrest. Some cases demonstrating such an arrest due to the indiscriminate use of this drug were recently reported. We continuously administered dexmedetomidine to a 56-year-old male patient at a rate of 0.3 µg/kg/h (lower than the recommended dose) without initial dosing for sedation in an intensive care unit. The patient had undergone open cardiac surgery and atrial pacing was maintained at a fixed rate, 90/min. The PQ interval in electrocardiography gradually prolonged during the infusion; finally, complete atrioventricular block and subsequent cardiac arrest occurred. Immediate cardiopulmonary resuscitation was carried out, including re-intubation, and recovery of spontaneous circulation was attained 15 min after the event. The patient was discharged from hospital on the 25th postoperative day without any neurological complications.

A prospective randomized multicenter comparative study of BLM-240 (desflurane) versus sevoflurane in Japanese patients.

The present study was conducted to evaluate the efficacy and safety of BLM-240 (desflurane) in comparison to sevoflurane in Japanese patients. A total of 216 patients were enrolled in this randomized comparative study at 15 medical institutions. The patients received either BLM-240 with 50-70 % N2O in O2 (n = 111), BLM-240 with 30 % O2 in air (n = 55), or sevoflurane with 50-70 % N2O in O2 (n = 50). Efficacy was evaluated by an efficacy rate based on an efficacy evaluation criteria and recovery time to extubation from the discontinuation of the anesthetics. Safety was evaluated by incidence of adverse drug reactions (ADR) and other clinical indicators. The efficacy rate of BLM-240 was 98.8 % (164/166 patients), indicating that BLM-240 is effective as an anesthetic. Time from discontinuation of anesthetic delivery to extubation was 9.7 ± 0.6 min in the BLM-240/N2O group and 14.3 ± 0.9 min in the sevoflurane/N2O group, meeting the pre-defined non-inferiority criteria of BLM-240 to sevoflurane. There was no statistically significant difference in the incidence of total ADR between the BLM-240 group (62.0 %) and sevoflurane group (48.0 %). The results indicate that BLM-240 is an effective and safe inhalation anesthetic in Japanese patients.

[A case of an unexpected difficult nasal intubation, caused by hypertrophied lingual tonsil].

We experienced a case of unexpected difficult nasal intubation due to lingual tonsil hyperplasia. A 43-year-old man was scheduled for pharyngoplasty because of sleep apnea syndrome. After induction of general anesthesia, Macintosh laryngoscopy failed to expose his glottis by two experienced anesthesiologists. We also found that the view of his larynx by fiberoptic bronchoscope (FOB) was poor, and nasal intubation guided by FOB was difficult. Finally, we made an oral intubation with Macintosh laryngoscopy under a gum elastic bougie guide. Ventilation and oxygenation were maintained throughout the procedure. A FOB guided intubation under general anesthesia is often difficult, because identification of glottis is interfered by deviated pharyngeal tissue and epiglottis, which are affected by the use of muscle relaxants. At present, a selective relaxant binding agent, sugammadex, is available in anesthesia, to reverse the effect of non-depolarizing muscle relaxant and to restore spontaneous breathing in this situation.

Bronchial intubation could be detected by the visual stethoscope techniques in pediatric patients.

BACKGROUND: We created a system that allows the visualization of breath sounds (visual stethoscope). AIM: We compared the visual stethoscope technique with auscultation for the detection of bronchial intubation in pediatric patients. METHODS: In the auscultation group, an anesthesiologist advanced the tracheal tube, while another anesthesiologist auscultated bilateral breath sounds to detect the change and/or disappearance of unilateral breath sounds. In the visualization group, the stethoscope was used to detect changes in breath sounds and/or disappearance of unilateral breath sounds. The distance from the edge of the mouth to the carina was measured using a fiberoptic bronchoscope. RESULTS: Forty pediatric patients were enrolled in the study. At the point at which irregular breath sounds were auscultated, the tracheal tube was located at 0.5 ± 0.8 cm on the bronchial side from the carina. When a detectable change of shape of the visualized breath sound was observed, the tracheal tube was located 0.1 ± 1.2 cm on the bronchial side (not significant). At the point at which unilateral breath sounds were auscultated or a unilateral shape of the visualized breath sound was observed, the tracheal tube was 1.5 ± 0.8 or 1.2 ± 1.0 cm on the bronchial side, respectively (not significant). CONCLUSIONS: The visual stethoscope allowed to display the left and the right lung sound simultaneously and detected changes of breath sounds and unilateral breath sound as a tracheal tube was advanced.

Dexmedetomidine and hydroxyzine synergistically potentiate the hypnotic activity of propofol in mice.

PURPOSE: Investigation into the characteristics of anesthetic interactions may provide clues to anesthesia mechanisms. Dexmedetomidine, an α(2)-adrenergic receptor agonist, has become a popular sedative in intensive care, and hydroxyzine, a histamine receptor antagonist, is well known as a tranquilizing premedication for anesthesia. However, no experimental or pharmacological evaluation has been reported concerning their combination with propofol. Thus, we studied their combined effect with a hypnotic dose of propofol in ddY mice. METHODS: Male adult mice were intravenously administered either dexmedetomidine (30 µg/kg) or hydroxyzine (5 mg/kg) with propofol (3.75-10 mg/kg) to induce hypnosis, defined as a loss of the righting reflex (LRR). Other mice were intravenously administered propofol, dexmedetomidine (300 µg/kg), or hydroxyzine (50 mg/kg) alone, and subsequent behavioral changes were observed. The 50% effective dose (ED(50)) for LRR was calculated, and the duration of LRR was determined. RESULTS: The hypnotic dose of propofol was 9.95 ± 1.04 mg/kg (ED(50) ± SEM) without combination. Dexmedetomidine and hydroxyzine reduced the ED(50) of propofol to 5.32 ± 0.57 and 5.63 ± 0.57 mg/kg, respectively. Coadministration of dexmedetomidine significantly extended LRR duration compared with propofol alone, whereas hydroxyzine significantly shortened LRR duration. A maximal dose of dexmedetomidine or hydroxyzine alone did not induce hypnosis. CONCLUSIONS: Dexmedetomidine and hydroxyzine demonstrated no hypnotic action alone; however, their coadministration potentiated the hypnotic activity of propofol. Although reduction in the dose of propofol was similar, only dexmedetomidine prolonged the duration of hypnosis.

[Sudden increases and decreases in bispectral index values more than 30 within 1 minute during general anesthesia].

We described, in a 40-year-old man, sudden and unexpected increases in bispectral index values during the general anesthesia with total intravenous anesthesia using propofol in a dental surgery. The patient was administered continuous infusion of propofol and remifentanil, and intermittent supplementation of fentanyl. Immediately after the beginning of surgery, the bispectral index value increased abruptly to 90; whereas, heart rate and non-invasive blood pressure were unchanged and no physiological finding was observed. Approximately 25 min later, the value decreased to below 40 without any modification of anesthesia. The extent of unanticipated increase might be compatible with the duration of surgical procedure using dental air turbine. Therefore, the noise from surgical device might induce unpredictable change in bispectral index values.

[Pycnodysostosis: a case report].

A 53-year-old man suffered maxillar osteomyelitis and removal of sequester was scheduled under general anesthesia. Pycnodysostosis had been diagnosed in childhood and body height and weight were 148 cm and 40 kg, respectively. He presented facial dysmorphia, hypomobile mandible and narrow oral cavity. At the pre-anesthetic visit, we planned awake fiberscopic intubation before the induction of general anesthesia. On the day of surgery, however, face-mask ventilation was easily established with 100-microg dose of fentanyl. Thus, 70 mg of propofol was administered to achieve hypnosis and naso-tracheal intubation using fibrescope was accomplished. The patient's trachea was easily intubated without a decrease of pulse oximetry values and marked changes in cardiovascular parameters. Pycnodysostosis is a rare clinical entity; however, the airway difficulty was mild in the present case.

The influence of endotoxemia on the electroencephalographic and antinociceptive effects of isoflurane in a swine model.

BACKGROUND: We have previously reported that hemorrhagic shock decreases the minimum alveolar anesthetic concentration (MAC) of isoflurane but minimally alters the electroencephalographic (EEG) effect. In this study, we investigated the influence of endotoxemia on the EEG effect and the MAC of isoflurane. METHODS: Eighteen swine (25.7 +/- 2.3 kg) were anesthetized by inhalation of isoflurane. The inhaled concentration was decreased to 0.5% and maintained for 20 min, before being returned to 2% and maintained for a further 20 min. End-tidal isoflurane concentrations and spectral edge frequencies were recorded. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for spectral edge frequencies versus effect-site concentration. After measurement of the EEG effect, MAC was determined using the dewclaw clamp technique in which movement in response to clamping is recorded. After completion of control measurements, infusion of lipopolysaccharide (LPS, 1 microg x kg(-1) x h(-1)) was started after a 100-microg bolus administration. After 1 h, the inhaled concentration of isoflurane was varied as in the control period, and the MAC was assessed again (LPS1h). The same procedures were also performed after 3 h of LPS infusion (LPS3h). RESULTS: Endotoxemia decreased the effect-site concentration that produced 50% of the maximal effect from 1.31% +/- 0.22% to 1.13% +/- 0.14% (LPS1h) and 1.03% +/- 0.22% (LPS3h) and decreased the MAC from 2.05% +/- 0.20% to 1.51% +/- 0.30% (LPS1h) and 1.21% +/- 0.29% (LPS3h). CONCLUSIONS: Endotoxemia increases both the hypnotic and antinociceptive effects of isoflurane, in contrast to hemorrhagic shock, and the extent of these alterations increases with progression of endotoxemia.