Early treatment with Fibrinogen γ-chain peptide-coated, ADP-encapsulated Liposomes (H12-(ADP)-liposomes) ameliorates post-partum hemorrhage with coagulopathy caused by amniotic fluid embolism in rabbits.

BACKGROUND: Amniotic fluid embolism is an unpredictable and sometimes lethal complication of childbirth. Fibrinogen γ-chain peptide-coated, ADP-encapsulated Liposomes (H12-(ADP)-liposomes), which were developed as a platelet substitute, may be useful to control postpartum hemorrhage with consumptive coagulopathy. OBJECTIVE: This study aimed to establish a hemodynamically stable amniotic fluid embolism animal model and evaluate the efficacy of H12-ADP-liposome infusion in the initial management of postpartum hemorrhage complicated with amniotic fluid embolism-involved coagulopathy. STUDY DESIGN: Pregnant New Zealand white rabbits (28th day of pregnancy or normal gestation period of 29-35 days) underwent cesarean delivery, followed by intravenous administration of amniotic fluid (a total of 3.0 mL administered in 4 doses over 9 minutes). Thereafter, uncontrolled postpartum hemorrhage was induced by transecting the right midartery and concomitant vein in the myometrium. After initial bleeding for 5 minutes, rabbits received isovolemic fluid resuscitation through the femoral vein with an equivalent volume of blood loss every 5 minutes for 60 minutes. The transfusion regimens included platelet-rich plasma, platelet-poor plasma, and a bolus administration of H12-ADP-liposomes followed by platelet-poor plasma transfusion (8 rabbits per group). Moreover, 60 minutes after initiation of bleeding, rabbits received surgical hemostasis by ligation of bleeding vessels, except in cases with spontaneous hemostasis. RESULTS: The administration of amniotic fluid caused thrombocytopenia (56±3 × 103/µL) and prolonged both clotting time (before administration: 130.0±3.0 to 171.0±5.0 seconds) and prothrombin time (4.5±0.1 to 4.7±0.1 seconds). After the initial 5-minute bleeding in the rabbits, the mean arterial pressure fell to 43±2 mm Hg. Platelet-poor plasma transfusion alone further prolonged clotting time and prothrombin time at 60 minutes (192.0±10.0 and 5.2±0.1 seconds, respectively) with decreasing mean arterial pressure to <40 mm Hg. By contrast, the administration of H12-ADP-liposomes followed by platelet-poor plasma transfusion reduced the prolonged clotting time (153.0±5.0 seconds) and prothrombin time (4.9±0.1 seconds) similar to platelet-rich plasma transfusion (154.0±11.0 and 4.9±0.1 seconds, respectively) at 60 minutes. These rabbits maintained a mean arterial pressure of >45 mm Hg throughout the experiment. H12-ADP-liposome infusion and platelet-poor plasma transfusion and platelet-rich plasma transfusion yielded spontaneous hemostasis in 4 of 8 rabbits, whereas platelet-poor plasma transfusion did not stop bleeding in any of the rabbits. The total blood loss was 59±17 mL in the H12-ADP-liposomes and platelet-poor plasma group, which was half of that in the platelet-poor plasma group (124±10 mL). CONCLUSION: H12-ADP-liposome infusion may be effective in the initial management of postpartum hemorrhage complicated with amniotic fluid embolism, resulting in mitigation of consumptive coagulopathy.

Resuscitative efficacy of hemoglobin vesicles for severe postpartum hemorrhage in pregnant rabbits.

We aimed to investigate the resuscitative efficacy of hemoglobin vesicles (HbVs) as a red blood cell (RBC) substitute for the initial treatment of severe postpartum hemorrhage (PPH). Twenty-five pregnant rabbits underwent cesarean section; uncontrolled hemorrhage was induced by transecting the right uterine artery to establish a severe PPH model. During the first 30 min, all rabbits were administered 6% hydroxyethyl starch (HES) of an equivalent volume to the hemorrhage every 5 min. Thereafter, they received any of the following three isovolemic fluids for resuscitation every 5 min: RBCs with platelet-poor plasma (RBC/PPP) (n = 8), 6% HES (n = 7), or HbVs with 25% human serum albumin (n = 10). After surgical hemostasis at 60 min, survival was monitored until 12 h. No rabbits receiving only HES infusion survived beyond 6 h, whereas all rabbits receiving RBC/PPP transfusion survived. The rabbits receiving HbV infusion showed significantly higher mean arterial pressure and hemoglobin levels than the HES-receiving rabbits, and 8 of 10 rabbits survived for 6 h. The HbV group showed significantly higher survival than the HES group but worse survival than the RBC/PPP group. In conclusion, HbV infusion for severe PPH effectively prevents lethal hemorrhagic shock in a pregnant rabbit model.

Efficacy of resuscitative infusion with hemoglobin vesicles in rabbits with massive obstetric hemorrhage.

BACKGROUND: Hemoglobin vesicles have been developed as artificial oxygen carriers, and they have the potential to serve as a substitute for red blood cell transfusion. OBJECTIVE: This study aimed to evaluate the efficacy of hemoglobin vesicle infusion for the initial treatment instead of red blood cell transfusion in rabbits with massive obstetric hemorrhage. STUDY DESIGN: Pregnant New Zealand white rabbits (28th day of pregnancy; normal gestation period, 29-35 days) underwent uncontrolled hemorrhage to induce shock by transecting the right midartery and concomitant vein in the myometrium. Subsequently, rabbits received isovolemic fluid resuscitation through the femoral vein with an equivalent volume of hemorrhage every 5 minutes. Resuscitative infusion regimens included 5% human serum albumin (n=6), stored washed red blood cells with plasma (vol/vol=1:1; n=5), and hemoglobin vesicle with 5% human serum albumin (vol/vol=4:1; n=5). A total of 60 minutes after the start of bleeding, rabbits underwent surgical hemostasis by ligation of the bleeding vessels and then were monitored for survival within 24 hours. RESULTS: During fluid resuscitation, hemoglobin vesicle infusion and red blood cell transfusion maintained a mean arterial pressure of >50 mm Hg and a hemoglobin concentration of >9 g/dL and prevented the elevation of plasma lactate. In contrast, resuscitation with 5% human serum albumin alone could not prevent hemorrhagic shock as evidenced by a low mean arterial pressure (40 mm Hg), a low hemoglobin concentration (2 g/dL), and a marked elevation of plasma lactate. All animals in the red blood cell group and the hemoglobin vesicle group survived more than 8 hours, whereas all animals in the 5% human serum albumin group died within 8 hours. CONCLUSION: Hemoglobin vesicle infusion may be effective in the initial management of massive obstetric hemorrhage.

Management of pregnancy and delivery in women with Kawasaki disease and residual coronary artery lesion with detailed analysis of labor analgesia: combined experience of 13 cases in two institutions.

INTRODUCTION: Approximately half of Kawasaki disease patients are expected to have transitioned to adulthood, and an increasing number of patients with cardiovascular sequelae have gotten pregnant. Management of women with Kawasaki disease who have residual coronary artery disease is poorly established. Thus, we conducted detailed analysis of these cases. METHODS: We reviewed 19 pregnancies in 13 such women in two tertiary perinatal facilities, Saitama Medical Center and National Cardiovascular Center. The medical records were reviewed in all women with Kawasaki disease and coronary artery lesion between 1998 and 2015, with regard to age of diagnosis, types of coronary artery lesion, location, previous treatment, pregnancy course and medical management for coronary lesion, cardiac function, and planned mode of delivery. RESULTS: Fourteen parturients attempted vaginal delivery, and all but one received neuraxial analgesia, providing stable hemodynamics. Four elective and two emergency cesarean deliveries were performed due to obstetric indications, while one woman required cesarean delivery at preterm due to maternal cardiac indication. Among 14 attempted vaginal deliveries, instrumental vaginal delivery was performed in 50%. Cardiac events were noted in four women, all in post-partum period, such as non-sustained ventricular tachycardia or chest discomfort without ECG changes. Antithrombotic medication was exclusively low dose aspirin in 11 of 19 pregnancies (58%), and none received anticoagulation during pregnancy or delivery. CONCLUSION: Our case series support the practice of preferred vaginal delivery, with neuraxial labor analgesia in indicated patients, while highlighting the need for vigilance in the post-partum period.

The first national survey of anesthesia techniques for fetal therapies in Japan.

PURPOSE: The aim of this study was to survey the frequency of various anesthetic techniques used in the anesthetic management of both the mother and fetus during fetal therapies in Japan. METHODS: We sent a postal survey to the institutions with physicians who held membership of the Japan Society of Fetal Therapy to describe maternal and fetal anesthetic management during fetal therapies performed from January 2016 to March 2017. The therapies included were thoracoamniotic shunting (TAS), intrauterine transfusion (IUT), radiofrequency ablation (RFA), fetoscopic laser photocoagulation (FLP), fetoscopic endotracheal occlusion (FETO), and ex utero intrapartum treatment (EXIT). Survey respondents were asked to specify the standard anesthetic technique used in each of these procedures done during the study period. RESULTS: The most common anesthetic techniques used in each therapy were sedation/analgesia with local anesthesia in TAS (31%), local anesthesia alone in IUT (47%), neuraxial anesthesia in RFA (50%), FLP (66%) and FETO (100%), and general endotracheal anesthesia in EXIT. Fetal analgesia was utilized in 61% of TAS, 33% of IUT, 10% of RFA, 22% of FLP, 100% of FETO, and 50% of EXIT. In all fetal therapies, the most common route of administration for fetal anesthesia was maternal administration. CONCLUSION: In this first published description of the frequency of various anesthetic techniques used during fetal therapies in Japan, we found that anesthetic techniques varied depending on the degree of invasiveness to the mother and fetus. Fetal anesthesia was not always performed, and the most common route for fetal anesthesia was maternal administration.

Postoperative renal function in parturients with severe preeclampsia who underwent cesarean delivery: a retrospective observational study.

Although postoperative renal dysfunction is relatively rare after cesarean delivery, preeclampsia is considered as the high-risk population. On the other hand, hydroxyethyl starch (HES) administration for preventing maternal hypotension induced by spinal anesthesia for cesarean delivery is a common practice. However, the effect of HES administration during cesarean delivery on postoperative kidney function in parturients with severe preeclampsia is not well investigated. We retrospectively reviewed both medical and anesthesia records of patients with severe preeclampsia who underwent cesarean delivery from January 2011 to December 2013. Preoperative blood examinations were compared with postoperative values. All parturients received 6% HES 70/0.5 for preventing anesthesia-induced hypotension or for volume resuscitation during cesarean delivery. A total of 87 severe preeclampsia parturients were underwent cesarean section during the period. The amounts of HES administration were 859 ± 206 mL. There was significant reduction in serum creatinine, from 0.70 ± 0.29 mg/dL preoperatively to 0.62 ± 0.17 mg/dL in 3-7 days after the cesarean. Only one patient had postoperatively elevated serum creatinine up to clinically significant level (from 0.64 mg/dL to 1.35 mg/kg).

A systematic review of massive transfusion protocol in obstetrics.

Post-partum obstetric haemorrhage is a leading cause of mortality among Japanese women, generally treated with haemostatic measures followed by supplementary transfusion. Commonly used in the setting of severe trauma, massive transfusion protocols (MTPs), preparations of red blood cell concentrate (RBC) and fresh frozen plasma (FFP) with additional supplements, have proved effective in decreasing patient mortality following major obstetric bleeding events. Although promising, the optimal configuration of RBC and FFP utilized for obstetric bleeding needs to be verified. Here, we conducted a systematic literature review to define the optimal ratio of RBC to FFP for transfusion therapy during instances of obstetric bleeding. Our analysis extracted four retrospective, observational studies, all demonstrating that an FFP/RBC ratio of ≥1 was associated with improved patient outcomes following obstetric haemorrhage. We therefore conclude that, from the standpoint of haemostatic resuscitation, an FFP/RBC ratio of ≥1 is a necessary condition for optimal clinical management during MTP administration in the field of obstetrics. Hence, we further propose an optimized MTP strategy to be utilized in the setting of severe obstetric bleeding.

Outcomes of labor epidural analgesia among women aged over 40: A single-institution retrospective study.

AIM: The purpose of this study was to investigate the effects of labor epidural analgesia (LEA) on maternal and neonatal outcomes among parturients aged 40 years or older. METHODS: We retrospectively reviewed medical records of all laboring, singleton and cephalic deliveries at ≥36 weeks' gestation at the Saitama Medical Center from April 2003 to September 2012. Women aged ≥40 years who received LEA (≥40 with LEA group) were compared with women aged ≥40 years who delivered without LEA (≥40 without LEA group) and women <40 years who received LEA (<40 with LEA group). Extracted outcomes included mode of delivery, oxytocin augmentation, duration of labor, amount of estimated blood loss, umbilical artery pH, Apgar scores, and neonatal intensive care unit admission. RESULTS: This study included 4441 women. There were 74 women in the ≥40 with LEA group, 369 in the ≥40 without LEA group, and 601 in the <40 with LEA group. The maternal outcomes of emergency cesarean delivery rate (9.5%, 12.5%, 9.0%), instrumental delivery rate (33.8%, 10.3%, 28.3%), duration of labor (521 min, 321 min, 565 min), and estimated blood loss (524 g, 351 g, 412 g) were reported for the ≥40 with LEA, ≥40 without LEA, and <40 with LEA groups, respectively. Neonatal outcomes were not different between these groups. LEA use was not associated with emergency cesarean delivery in the multivariable analysis. CONCLUSION: Our study showed that parturients aged ≥40 with LEA can expect similar LEA-associated labor outcomes to younger parturients with LEA.

Pre-delivery fibrinogen predicts adverse maternal or neonatal outcomes in patients with placental abruption.

AIM: Placental abruption is a severe obstetric complication of pregnancy that can cause disseminated intravascular coagulation and progress to massive post-partum hemorrhage. Coagulation disorder due to extreme consumption of fibrinogen is considered the main pathogenesis of disseminated intravascular coagulation in patients with placental abruption. The present study sought to determine if the pre-delivery fibrinogen level could predict adverse maternal or neonatal outcomes in patients with placental abruption. METHODS: This retrospective medical chart review was conducted in a center for maternal, fetal, and neonatal medicine in Japan with 61 patients with placental abruption. Fibrinogen levels prior to delivery were collected and evaluated for the prediction of maternal and neonatal outcomes. The main outcome measures for maternal outcomes were disseminated intravascular coagulation and hemorrhage, and the main outcome measures for neonatal outcomes were Apgar score at 5 min, umbilical artery pH, and stillbirth. RESULTS: The receiver-operator curve and multivariate logistic regression analyses indicated that fibrinogen significantly predicted overt disseminated intravascular coagulation and the requirement of ≥6 red blood cell units, ≥10 fresh frozen plasma units, and ≥20 fresh frozen plasma units for transfusion. Moderate hemorrhage occurred in 71.5% of patients with a decrease in fibrinogen levels to 155 mg/dL. Fibrinogen could also predict neonatal outcomes. Umbilical artery pH < 7.00 occurred in 77.1% of patients with a decrease in fibrinogen levels to ≤ 250 mg/dL. CONCLUSION: Pre-delivery fibrinogen can predict adverse maternal as well as neonatal outcomes with placental abruption. © 2016 Japan Society of Obstetrics and Gynecology.

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.

Successful resuscitation of amniotic fluid embolism applying a new classification and management strategy.

Amniotic fluid embolism (AFE) is a rare but life-threatening maternal emergency caused by the entry of amniotic fluid contents into the maternal circulation. The clinical manifestations of AFE are heterogeneous, leading to misdiagnosis or treatment delay. Kanayama and colleagues distinguished the cardiopulmonary collapse type (or classic type) from the disseminated intravascular coagulation (DIC) type of AFE on the basis of the presence of uterine atony and DIC in the latter prior to cardiopulmonary failure. We report a case of DIC-type AFE successfully treated by blood volume replacement and coagulation therapy. The patient was scheduled for elective cesarean delivery because of a previous cesarean section and moyamoya disease. Delivery was uneventful, but massive vaginal bleeding without clotting and ensuing hypovolemic shock occurred 4 h later. She was transferred to the operating room for emergency laparotomy, but sustained a cardiac arrest. The patient was successfully resuscitated and a hysterectomy performed. During surgery, the patient received fresh frozen plasma, platelets, fibrinogen, and antithrombin concentrate. In cardiopulmonary collapse type AFE, cardiopulmonary resuscitation without delay is important. In the present case of DIC-type AFE, however, early supplementation of clotting factors and platelets was critical for patient survival.

Incidence and prediction of outcome in hypoxic-ischemic encephalopathy in Japan.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is one of the most critical pathologic conditions in neonatal medicine due to the potential for neurological deficits in later life. We investigated the incidence of term infants with moderate or severe HIE in Japan and identified prognostic risk factors for poor outcome in HIE. METHODS: Data on 227 infants diagnosed with moderate or severe HIE and born between January and December 2008 were collected via nationwide surveys from 263 responding hospitals. Using logistic regression, we examined the relationship between maternal, antepartum, intrapartum, and neonatal risk factors and clinical outcome at 18 months following birth. RESULTS: In Japan, the incidence of moderate or severe HIE was 0.37 per 1000 term live births. Outborn births, low Apgar score at 5 min, use of epinephrine, and low cord blood pH were intrapartum factors significantly associated with neurodevelopmental delay and death at 18 months. Serum lactate, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase (all, P < 0.001) and creatine kinase (P = 0.002) were significantly higher in infants with poor outcome compared to those with favorable outcomes. Abnormal brain magnetic resonance imaging (MRI), an important prognostic factor, was significantly associated with poor outcome (odds ratio, 11.57; 95% confidence interval: 5.66-23.64; P < 0.001). CONCLUSIONS: Risk factors predicting poor outcome in HIE include outborn birth, low Apgar score at 5 min, use of epinephrine, laboratory abnormalities, and abnormal MRI findings.

Success rate and challenges of fetal anesthesia for ultrasound guided fetal intervention by maternal opioid and benzodiazepine administration.

OBJECTIVE: The safe and effective methods of fetal anesthesia/analgesia during ultrasound guided direct fetal procedure are yet to be determined. The authors investigated whether maternal diazepam/fentanyl administration meets this purpose. METHODS: The medical/anesthesia records were retrospectively reviewed in cases between 2001 and 2010 at a tertiary perinatal center. Success rate as well as maternal and fetal complications were analysed. RESULTS: Among the 150 procedures in 118 fetuses, diazepam 10 mg and fentanyl 200 µg sufficiently prevented fetal movement upon the procedure in 56% of the procedures. Supplemental anesthetic agents such as nitrous oxide and propofol were needed in other cases. No serious maternal complication was noted, while fetal cardiac arrest/severe bradycardia was noted in three fetuses, one of which was successfully resuscitated by intracardiac adrenalin injection. CONCLUSIONS: Maternal diiazepam/fentanyl administration offered adequate fetal condition without significant maternal complications. Since these procedures are performed to treat severe fetal conditions, preparation for fetal resuscitation is also important.

Fluid therapy with hydroxyethyl starch for massive blood loss during surgery.

PURPOSE: This clinical trial reports the use of hydroxyethyl starch (HES70/0.55/4) at very high dosages during surgery. HES70/0.55/4 has the lowest molecular weight among all HES products, and thus may have the least side effects. This observational retrospective study clarified the effects of high-dose HES70/0.55/4 on coagulation and renal function up to 1 month after massive bleeding during surgery. METHODS: Of 20875 patients on our surgical database, 31 patients were identified who had lost more than 5000 ml of blood during surgery and had survived for more than 1 month. The fluid balance, and pre- and postoperative laboratory data were analyzed. Patients were assessed using acute kidney injury (AKI) criteria. AKI and non-AKI groups were compared regarding volume of HES70/0.55/4 infused and serum creatinine (Cr) levels before surgery and until 1 month after surgery. RESULTS: The mean volumes of blood loss, total transfusions, HES70/0.55/4, and urine output during surgery were 8051 ml; 5765 ml; 3085 ml (54 ml/kg); and 1338 ml (2.7 ml/kg/h), respectively. Cr increased, and activated partial thromboplastin time, prothrombin time and international normalized ratio were prolonged postoperatively (0.77-0.9 mg/dl, 34-52 s, and 1.1-1.7, respectively). Of the 31 patients, 13 developed AKI, and 10 of the 13 had recovered at 1 month. Renal impairment due to HES70/0.55/4 was not evident, as shown by the finding that the HES70/0.55/4 amount infused in the AKI patients (53 ml/kg) did not differ from that in the nonAKI patients (55 ml/kg), and there was no relationship between the amount of HES infused and Cr changes. CONCLUSION: High-dose HES70/0.55/4 could be safely used in massive bleeding during surgery. HES70/0.55/4 may affect coagulation, but renal impairment was not evident 1 month after surgery.

[Obstetric anesthesia: from basics to recent advances in neontatal resuscitation: from Apgar score to NCPR program].

Attempt to resuscitate asphyxiated neonates dates back to 1940's described in the Japanese obstetric textbook. These resuscitation methods simply employed moving the chest by applying external forces, such as bending the torso or flipping over the baby's body. In 1953, Virginia Apgar, an obstetric anesthesiologist, proposed her score to assess newborn status, which has been used worldwide thereafter. American Academy of Pediatrics and American Heart Association developed neonatal resuscitation guidelines in 1980's, the most recent guideline having been issued in 2005. The Japanese Society of Perinatal and Neonatal Medicine modified this guideline and started training courses for neonatal cardiopulmonary resuscitation (NCPR). Many resuscitation skills and medications are familiar to anesthesiologists, and many anesthesiologists are expected to be certified in NCPR in the future. Guideline is to be revised on regular basis, as the scientific and clinical evidence accumulates, and the next one will likely recommend reduced FI(O2) during resuscitation.

Buccal administration of dexmedetomidine as a preanesthetic in children.

PURPOSE: The objective of this study was to evaluate the efficacy and safety of buccal dexmedetomidine as a preanesthetic in children, to compare it with diazepam, and to investigate the optimal dosage for buccal dexmedetomidine administration by measuring its serum concentration. METHODS: We performed a prospective study with 40 children who were assigned to two groups. The patients underwent an operation for inguinal or umbilical hernia. Twenty children received dexmedetomidine buccally at 3-4 microg/kg (Dex Group) and 20 received a diazepam suppository at 0.7 mg/kg (Diazepam Group) as preanesthetics 1 h before the operation. Heart rate, systolic blood pressure, SpO2, and respiratory rate were measured 1 h after premedication in all children. Sedation level was preoperatively evaluated, and compared with the Ramsay score, in the ward, at the entrance to the main operating rooms, and at anesthesia induction between the two groups. To investigate the optimal dosage of buccal dexmedetomidine, we compared the mean serum concentration of dexmedetomidine at induction between patients with a Ramsay score of 5 or greater and those with a Ramsay score less than 5. The Mann-Whitney U test was used for statistical analysis. RESULTS: There was no significant difference between the two groups in age or body weight. Furthermore, there was no significant difference between the two groups in heart rate, systolic blood pressure, SpO2, or respiratory rate after administration of either medication. The Ramsay score of the Dex Group was significantly higher than that of the Diazepam Group at all times. The mean serum dexmedetomidine concentration at induction in patients with a Ramsay score of 5 or greater (75 +/- 50 pg/ml) was significantly higher than in those with a Ramsay score less than 5 (34 +/- 36 pg/ml, P < 0.05). CONCLUSION: These results suggest that the buccal administration of dexmedetomidine (3-4 microg/kg) 1 h before the operation can be safely and effectively applied as a preanesthetic in children.