[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.

Time-dependent changes in epidural catheter aspirate after injection of a local anesthetic.

STUDY OBJECTIVE: A glucose check is used for investigation of a suspected accidental dural puncture in epidural anesthesia. However, glucose-positive clear fluid is sometimes aspirated from an epidural catheter in cases without clinical evidence of puncture. The goal of the study was to investigate time-dependent changes in the aspirate composition after injection of a local anesthetic into the epidural space. DESIGN: Observational study. SETTING: Operating rooms at Hamamatsu University Hospital. PATIENTS: The subjects were 30 patients (ASA I or II) undergoing surgery with combined epidural and general anesthesia. INTERVENTIONS: After epidural injection of local anesthetics, aspiration through the catheter was performed every 10min until fluid could not be aspirated. pH, Na, K, Cl, Ca and glucose were measured in fluid samples using a blood gas analysis apparatus. MAIN RESULTS: No patients had pain or clinical signs suggesting dural puncture throughout the perioperative period. Fluid aspiration was possible in 15 patients (50%) after 10min and in 7, 3, 2 and 2 patients after 20, 30, 40 and 50min, respectively. Glucose was detected in each aspirated fluid sample and gradually increased with time to become closer to the level in cerebrospinal fluid (CSF). Each electrolyte also changed to approach the level found in CSF. CONCLUSIONS: A glucose check may increase the risk of a false-positive finding for accidental dural puncture with increasing time after local anesthetic injection. Conversely, detection of glucose at the time of epidural catheter placement may provide useful information for detection of accidental dural puncture.

[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.

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.

Four-Group Classification Based on Fibrinogen Level and Fibrin Polymerization Associated With Postoperative Bleeding in Cardiac Surgery.

Fibrinogen and fibrin formation have a key role in perioperative hemostasis. The aim of this study is to examine the association of postoperative hemostasis with a combined evaluation of the fibrinogen level and fibrin polymerization in cardiac surgery. We retrospectively classified 215 consecutive cardiac surgery patients into 4 groups (Fuji-san classification) that were divided by fibrinogen level <150 mg/dL (ie, hypofibrinogenemia) and fibrinogen thromboelastometry value at 10 minutes with rotational thromboelastometry <6 mm (ie, low fibrin polymerization) at the warming of cardiopulmonary bypass. Four groups resulted; group I, the acceptable range (n = 85); group II, only hypofibrinogenemia (<150 mg/dL, ≥6 mm, n = 63); group III, hypofibrinogenemia and low fibrin polymerization (<150 mg/dL, <6 mm, n = 60); and group IV, only low fibrin polymerization (≥150 mg/dL, <6 mm, n = 7). The risk of chest tube drainage volume greater than 500 mL within the first 24 hours after surgery (with group I as the reference) was increased in group II (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.5-7.4; P < .01) and group III (OR, 8.5; 95% CI, 3.5-21.7; P < .01), and the risk greater than 1000 mL (with group I as the reference) was increased in group III (OR, 4.0; 95% CI, 1.1-17.3; P = .03) and group IV (OR, 23.1; 95% CI, 3.2-201.0; P < .01). Intraoperative blood transfusions were decreased by 24.5%, after stratifying the starting amount of fresh frozen plasma by the 4-group classification in the recent consecutive 65 (30.2%) patients (P < .01). The 4-group classification is associated with postoperative bleeding and may improve the quality of perioperative blood transfusion in cardiac surgery.

[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.

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.

Successful serial imaging of the mouse cerebral arteries using conventional 3-T magnetic resonance imaging.

Serial imaging studies can be useful in characterizing the pathologic and physiologic remodeling of cerebral arteries in various mouse models. We tested the feasibility of using a readily available, conventional 3-T magnetic resonance imaging (MRI) to serially image cerebrovascular remodeling in mice. We utilized a mouse model of intracranial aneurysm as a mouse model of the dynamic, pathologic remodeling of cerebral arteries. Aneurysms were induced by hypertension and a single elastase injection into the cerebrospinal fluid. For the mouse cerebrovascular imaging, we used a conventional 3-T MRI system and a 40-mm saddle coil. We used non-enhanced magnetic resonance angiography (MRA) to detect intracranial aneurysm formation and T2-weighted imaging to detect aneurysmal subarachnoid hemorrhage. A serial MRI was conducted every 2 to 3 days. MRI detection of aneurysm formation and subarachnoid hemorrhage was compared against the postmortem inspection of the brain that was perfused with dye. The imaging times for the MRA and T2-weighted imaging were 3.7±0.5 minutes and 4.8±0.0 minutes, respectively. All aneurysms and subarachnoid hemorrhages were correctly identified by two masked observers on MRI. This MRI-based serial imaging technique was useful in detecting intracranial aneurysm formation and subarachnoid hemorrhage in mice.

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.

Landiolol reduces hemodynamic responses to bronchoscopy-assisted suctioning in intubated ICU patients.

Landiolol is an ultra-short-acting ß1-selective antagonist developed in Japan that was recently approved for the treatment of tachycardia in intensive care units (ICUs). This study investigated the protective effects of landiolol against the cardiovascular responses during bronchoscopic endotracheal suctioning. This study enrolled 15 patients requiring orotracheal intubation in an ICU. All of the patients required endotracheal suctioning using fiber bronchoscopy while sedated at a Ramsay Scale of 2-3. All subsequent suctioning procedures were assigned randomly to three groups using a cross-over design: saline as a placebo (group C) or 20 or 40 µg kg(-1) min(-1) landiolol, respectively (groups L20 and L40). The infusion was started 3 min before bronchoscopy and continued for 6 min. The central venous pressure (CVP) heart rate (HR) and arterial blood pressure (BP) were recorded. Fourteen patients completed the investigation, and 30 procedures (n = 10/group) were analyzed. The suctioning significantly increased the CVP, HR, and BP in groups C and L20, although the changes in BP were of shorter duration in group L20. No significant increase in the hemodynamic parameters was observed in group L40. The administration of landiolol 40 µg kg(-1) min(-1) prevented a harmful hyperdynamic circulatory response to bronchoscopic endotracheal suctioning, without obvious decreases in HR or BP after the intervention.

Continuous administration of landiolol reduced QT dispersion in postoperative patients.

STUDY OBJECTIVE: To determine the changes in QT dispersion (QTD) in the standard electrocardiogram (ECG) of postoperative patients and the effect of landiolol on QTD. DESIGN: Randomized, prospective, double-blinded study. PATIENTS: 40 postsurgical patients. INVENTIONS: Patients were allocated to three groups: Control group patients (Group C) were administered saline and patients in the landiolol groups (Group L2 and Group L5) were infused landiolol 2 µg/kg/min and 5 µg/kg/min, respectively. All infusions were started at midnight and discontinued at 6 o'clock in the morning. MEASUREMENTS: Heart rate (HR), systolic (SBP) and diastolic (DBP) invasive blood pressure, and ECG were recorded at 0 (immediately before infusion), at 3 o'clock, and 6 o'clock (immediately before termination). The ECG wave was recorded electronically and QTD was analyzed using PC software. Heart rate, blood pressure, QT interval, and QTD were compared as changes from baseline values. MAIN RESULTS: In Groups L2 and L5, HR was significantly decreased, approximately 10 bpm. Both SBP and DBP showed a decreasing trend at 3 o'clock. Absolute QT interval was prolonged in all groups; however, the decrease in QTD occurred in Group L5. CONCLUSIONS: Continuous administration of landiolol prevents the increase in QTD found on the morning in postoperative patients. Landiolol demonstrated a possible antiarrhythmic effect by improving the imbalance of repolarization.

Hypocapnia delays subsequent bupivacaine cardiotoxicity in rats under sevoflurane anesthesia.

BACKGROUND: Hypocapnia induced following the accidental intravenous infusion of a local anesthetic can mitigate anesthetic toxicity, but the effects of hypocapnia induced prior to local anesthetic infusion are unknown. In this study, we examined the effects of prior hypocapnia on bupivacaine-induced cardiotoxicity in rats. METHODS: Eighteen Sprague-Dawley rats were randomly divided into two groups: one receiving sevoflurane with normal ventilation (Control Group) and the other receiving sevoflurane with hyperventilation to induce hypocapnia (Hypocapnia Group). After 30 min, both groups received continuous intravenous infusions of 0.25% bupivacaine at 2 mg · kg(-1) · min(-1). The time taken to reach 25% and 50% reductions in heart rate (HR; HR-25%, HR-50%) and mean arterial pressure (MAP; MAP-25%, MAP-50%) from the start of bupivacaine infusion were recorded. The difference between HR-25% and MAP-25% was calculated. The times of the first ventricular premature beat (VPB) and final systole were also recorded. RESULTS: In the Hypocapnia Group, HR-50%, MAP-25%, and MAP-50% were prolonged compared with the Control Group (P < 0.001). Furthermore, the interval between HR-25% and MAP-25% and the times between the first VPB and final systole were prolonged in the Hypocapnia Group (P < 0.001). CONCLUSION: In rats under sevoflurane anesthesia, prior hypocapnia delayed the onset of bupivacaine-induced cardiotoxicity. Prior hypocapnia should be avoided during continuous bupivacaine nerve block under general anesthesia, because it may delay the detection of cardiotoxicity.

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.

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.

The characteristics of postoperative fentanyl effect-site concentration during intravenous fentanyl analgesia after posterior lumbar spine fusion.

OBJECTIVE: To examine the characteristics of postoperative fentanyl effect-site concentrations during intravenous analgesia in patients requiring or not requiring a fentanyl bolus and in patients with or without postoperative nausea and vomiting (PONV). DESIGN: Retrospective observational study. SETTING: University-affiliated general hospital. PATIENTS: Sixty patients who underwent posterior lumbar spine fusion. MAIN OUTCOME MEASURES: The authors simulated the fentanyl effect-site concentration for 48 postoperative hours and compared it between patients who did and did not require a fentanyl bolus and between patients who did and did not experience PONV. RESULTS: At the end of anesthesia, the fentanyl effect-site concentration was similar between 37 (61.7 percent) patients requiring and 23 (38.3 percent) patients not requiring a postoperative fentanyl bolus (p=0.97). Within the first 12 postoperative hours, the concentration decreased in both groups (p < 0.01). The fentanyl effect-site concentration was higher in patients requiring a postoperative fentanyl bolus (within 12 hours, 1.4 ± 0.32 ng/mL vs 0.89 ± 0.35 ng/mL; between 12 and 48 hours, 0.94 ± 0.19 ng/mL vs 0.57 ± 0.09 ng/mL) (p < 0.05). PONV occurred in 22 (36.6 percent) patients, but more so in women (68.2 percent; p < 0.01); PONV was similar between patients requiring and not requiring a fentanyl bolus (p=0.78). Between the 12th and 48th postoperative hours, fentanyl effect-site concentrations were higher in patients with PONV (0.61 ± 0.10 ng/mL vs 0.57 ± 0.10 ng/mL, p=0.03). CONCLUSIONS: Patients needing a postoperative fentanyl bolus require a higher fentanyl effect-site concentration possibly because of individual variations, and PONV depends on the postoperative fentanyl effect-site concentration.