A novel step-down infusion method of barbiturate therapy: Its safety and effectiveness for intracranial pressure control.

Intracranial pressure (ICP) has to be maintained quite constant, because increased ICP caused by cerebrovascular disease and head trauma is fatal. Although controlling ICP is clinically critical, only few therapeutic methods are currently available. Barbiturates, a group of sedative-hypnotic drugs, are recognized as secondary treatment for controlling ICP. We proposed a novel "step-down infusion" method, administrating barbiturate (thiamylal) after different time point from the start of treatment under normothermia, at doses of 3.0 (0-24 h), 2.0 (24-48 h), 1.5 (48-72 h), and 1.0 mg/kg/h (72-96 h), and evaluated its safety and effectiveness in clinical. In 22 patients with severe traumatic brain injury or severe cerebrovascular disease (Glasgow coma scale ≤8), thiamylal concentrations and ICP were monitored. The step-down infusion method under normothermia maintained stable thiamylal concentrations (<26.1 µg/ml) without any abnormal accumulation/elevation, and could successfully keep ICP <20 mmHg (targeted management value: ICP <20 mmHg) in all patients. Moreover the mean value of cerebral perfusion pressure (CPP) was also maintained over 65 mmHg during all time course (targeted management value: CPP >65 mmHg), and no threatening changes in serum potassium or any hemodynamic instability were observed. Our novel "step-down infusion" method under normothermia enabled to maintain stable, safe thiamylal concentrations to ensure both ICP reduction and CPP maintenance without any serious side effects, may provide a novel and clinically effective treatment option for patients with increased ICP.

Pediatric procedural sedation in Japan: A single-facility study of 1,436 cases.

BACKGROUND: Pediatric procedural sedation (PPS) has been established worldwide as standard practice for several decades. However, there are no comprehensive guidelines or multi-facility databases of PPS in Japan, and the current status of PPS and PPS-related adverse events is unclear. The objectives of this study were to investigate the status of PPS in Japan and clarify the adverse events and risk factors. METHODS: This study was a single-facility, database survey performed at Oita University Hospital from September 2016 to March 2019. Children under 18 years of age who had been kept sedated for medical procedures with intravenous sedatives were enrolled in this study. Adverse events were recorded and defined according to the Quebec Guideline. RESULTS: During the study period, PPS was performed for 1,436 consecutive cases. The majority (94%) of the sedatives used were thiamylal alone or thiamylal combined with ketamine. There were a total of 253 adverse events in 233 cases (16.2%), including oxygen desaturation, airway hypersensitivity, and vomiting. Patients recovered from respiratory-related adverse events immediately with simple intervention. No patient required endotracheal intubation and no severe adverse event occurred. Four risk factors (a higher American Society of Anesthesiologists classification, longer procedure time, non-compliance of nil per os status, and no Pediatric Advanced Life Support certification for sedation personnel) were associated with the occurrence of adverse events. CONCLUSIONS: Adverse events occurred in 16.2% of all PPS cases. Further studies are needed to analyze the serious adverse events and risk factors for PPS in Japan.

Efficacy and safety of intravenous thiamylal in pediatric procedural sedation for magnetic resonance imaging.

OBJECTIVE: To evaluate the efficacy and safety of intravenous (i.v.) thiamylal in pediatric magnetic resonance imaging (MRI) sedation. METHODS: Infants and children from 1 month up to 8 years of age who underwent MRI in our hospital between April 2017 and March 2019 were included in this prospective observational study. Initial dose of 2 mg/kg thiamylal was given intravenously; however, additional doses were administered as needed. MRI was performed after adequate sedation was achieved. The primary endpoint was the success rate of MRI, while secondary endpoints were adverse events related to sedation, time to sedate, recovery time, and the dose of thiamylal. RESULTS: A total of 118 patients were included in the analysis with median age and weight of 31.5 months (14.0-56.8 months) and 12.6 kg (9.5-15.7 kg), respectively. The success rate of MRI was 96.6% (114/118), and the median dose of thiamylal per body weight was 3.6 (2.8-4.0) mg/kg. The median time from the first dose of thiamylal to MRI was 7 min (4-10 min) and that from the end of MRI scanning to the confirmation of emergence was 8 min (5-25 min). Adverse events encountered included respiratory arrests (n = 3) and reduction in oxygen saturation (SpO2; n = 9). There were no significant differences in the age, dose of thiamylal, sex, body weight, the American Society of Anesthesiologists physical status, and neurological abnormalities between the groups with and without respiratory complications. CONCLUSION: This study demonstrated an adequate efficacy and safety of i.v. thiamylal, with rapid sedation and patient recovery.

Thiamylal Plus Pentazocine Shows Similar Efficacy as Ketamine Plus Midazolam for Painful Procedures in Children With Leukemia.

This retrospective study compared the use of thiamylal plus pentazocine (TP) to ketamine plus midazolam (KM) in children with leukemia who were undergoing bone marrow aspiration and/or intrathecal chemotherapy. A total of 268 procedures in 35 children with leukemia were retrospectively analyzed for efficacy and adverse events. All procedures were successfully completed without severe adverse events. TP induced significantly faster sedation. The incidents of desaturation were significantly greater in the TP group, but were transient and recovered by oxygen supplementation alone. Therefore, TP can be a useful combination with a similar efficacy as KM for painful procedures in children.

The influence of glucose load on metabolism during minor surgery using remifentanil-induced anesthesia.

BACKGROUND: During perioperative fasting, lipid metabolism gradually increases, resulting in free fatty acids (FFA) and/or ketone bodies. Suppression of surgical stress by remifentanil may allow the safe administration of glucose infusions, avoiding both hyperglycemia and ketogenesis. The effects of glucose infusion on glucose and lipid metabolism were therefore investigated in patients undergoing minor surgery with remifentanil anesthesia. METHODS: Thirty-four patients were randomized 1 : 1 to receive no glucose (0G group) or low-dose glucose (0.1 g/kg/h for 1 h followed by 0.05 g/kg/h for 1 h; LG group). The concentrations of glucose, adrenocorticotropic hormone (ACTH), 3-methylhistidine (3-MH), insulin, cortisol, FFA, creatinine (Cr), and ketone bodies were measured before anesthetic induction, 1 and 2 h after glucose infusion, at the end of surgery, and the next morning. RESULTS: The concentrations of cortisol and ACTH decreased during surgery in both groups when compared with the concentrations before anesthesia and at the end of surgery (P < 0.05). Glucose and insulin concentrations were significantly higher in the LG than in the 0G group at 1 and 2 h after infusion. No patient experienced hyperglycemia. The concentrations of FFA and ketone bodies were lower in the LG than in the 0G group during surgery, but there were no significant between group differences in 3-MH/Cr. CONCLUSION: Infusion of low-dose glucose attenuated fat catabolism without causing hyperglycemia, indicating that infusion of low-dose glucose during remifentanil-induced anesthesia may be safe for patients.

Procedural sedation with dexmedetomidine during ablation of atrial fibrillation: a randomized controlled trial.

AIMS: Procedural sedation by non-anaesthesiologists with GABAergic anaesthetics has the potential risk of fatal respiratory depression. Dexmedetomidine works its sedative action via α2-adrenergic receptors, and is less associated with respiratory depression. We tested the usability of dexmedetomidine as a procedural sedative during ablation of atrial fibrillation (AF). METHODS AND RESULTS: Consecutive patients were randomized to be treated with dexmedetomidine (n = 43) or thiamylal (n = 44) as sedatives during AF ablation. Apnoeic and body movement events were monitored using a novel portable respiratory monitor, the SD-101, during the procedure. Although the majority of the patients receiving dexmedetomidine required rescue sedations with thiamylal, the respiratory disturbance index (RDI) defined as the total number of sleep-disordered breathing events divided by the recording time (10.4 ± 5.1 vs. 18.2 ± 8.1 events/h; P < 0.0001) and movement index defined as the number of body movement events per hour (7.6 ± 6.1 vs. 11.0 ± 5.5 events/h; P = 0.0098) were both significantly lower in the dexmedetomidine arm than in the thiamylal arm. A multivariate linear regression analysis including potential factors revealed that dexmedetomidine vs. thiamylal was solely and independently associated with the RDI (ß = -0.62; P = 0.0031). The occurrence of hypotension [9 (21%) vs. 4 (9%); P = 0.14] and bradycardia [4 (9%) vs. 4 (9%); P = 1.0] were similar in the patients with dexmedetomidine and thiamylal. CONCLUSION: Procedural sedation with dexmedetomidine may assure safety and patient immobility during AF ablation, and therefore may be a potential alternative for that with GABAergic anaesthetics.

A comparison of the effect on QT interval between thiamylal and propofol during anaesthetic induction*.

SUMMARY: The aim of this study was to determine the effect of thiamylal and propofol on heart rate-corrected QT (QTc) interval during anaesthetic induction. We studied 50 patients undergoing lumbar spine surgery. Patients were administered 3 microgxkg(-1) fentanyl and were randomly allocated to receive 5 mgxkg(-1) thiamylal or 1.5 mgxkg(-1) propofol as an induction agent. Tracheal intubation was performed after vecuronium administration. Heart rate, mean arterial pressure, bispectral index score, and 12-lead electrocardiogram were recorded at the following time points: just before (T1) and 2 min after (T2) fentanyl administration; 2 min after anaesthetic administration (T3); 2.5 min after vecuronium injection (T4); and 2 min after intubation (T5). Thiamylal prolonged (p < 0.0001), but propofol shortened (p < 0.0001), the QTc interval.

Intravenous thiamylal and local anesthetic infiltration for pediatric facial repair procedures performed in emergency departments.

Thiamylal is widely used for procedural sedation in emergency departments (ED); however, there are limited safety data for doses of thiamylal > 5 mg/kg in children. We investigated whether intravenous thiamylal in combination with local anesthetics is safe and effective for pediatric procedural sedation in the ED and to identify the association between increasing doses thiamylal and adverse events. Between July 2004 and June 2008, 227 children who underwent procedural sedation met the inclusion criteria, including 105 males (46.3%) and 122 females (53.7%). Facial laceration was the most common indication for procedural sedation. All children received an intravenous injection of thiamylal, with a loading dose of 5 mg/kg. Eighty-one children (35.7%) received a supplemental dose of 2.5 mg/kg thiamylal because of inadequate sedation. Of these, 27 (11.9%) received a second supplemental dose of 2.5 mg/kg because of inadequate sedation. Sixty-six patients (29.1%) experienced 75 mild and self-resolving adverse events, and most of which (15/75; 20%) were drowsiness. Four (1.8%) patients experienced oxygen saturation below 96%, which was related to the supplemental dose of thiamylal (p = 0.002). No children suffered from any lasting or potentially serious complications. Our results indicate that intravenous thiamylal in combination with local anesthetic infiltration is a well tolerated for therapeutic procedures in the ED. Thiamylal offers rapid onset of sedation without compromising the patient's cardiorespiratory function during pediatric procedural sedation.

Efficacy and adverse effects of rectal thiamylal with oral triclofos for children undergoing magnetic resonance imaging.

We studied the efficacy and adverse effects of rectal thiamylal in combination with oral triclofos in sedation for pediatric magnetic resonance imaging. Five hundred forty-six children underwent MRI examination from January of 1997 to December of 2001. Among them, 10mg/kg of rectal thiamylal was administrated after oral triclofos in 378 children. Successful sedation was obtained in 321 of 378 patients (85%) after a single rectal administration of thiamylal. Totally, 369 children (98%) could undergo MRI examination completely under successful sedation. Adverse effect was observed only in one patient showing respiratory depression. Rectal thiamylal is effective for sedation for MRI in children. Adverse effect was rare in our patients. Although the risk of side effect was considered to be rare, we should follow principles for the sedation of children.

Intravenous alprostadil, an analog of prostaglandin E1, prevents thiamylal-fentanyl-induced bronchoconstriction in humans.

UNLABELLED: Prostaglandin (PG) E(1) relaxes airway smooth muscle in animals. However, no clinical data have been published on the bronchorelaxant effects of IV alprostadil, an analog of PGE(1). We have described experimental thiamylal-fentanyl-induced bronchoconstriction in humans; we now report the effect of IV alprostadil on thiamylal-fentanyl-induced bronchoconstriction. Thirty-two patients were allocated randomly to a control group (n = 16) and alprostadil group (n = 16). Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.3 mg/kg and maintained with a continuous infusion of thiamylal 15 mg. kg(-1). h(-1). The lungs of the patients were ventilated with 50% nitrous oxide in oxygen. Twenty minutes after the induction of anesthesia, patients in the control group were given a continuous infusion of normal saline 20 mL/h, and those in the alprostadil group received a continuous infusion of alprostadil 0.2 micro g. kg(-1). min(-1) (20 mL/h), both for 60 min. Both groups were then given fentanyl 5 micro g/kg. Systolic and diastolic arterial blood pressure, heart rate, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured at the baseline, just before the fentanyl injection (T30), at three consecutive 6-min intervals after fentanyl injection (T36, T42, and T48), and 30 min after fentanyl injection (T60). Baseline Rawm, Rawe, and Cdyn values were comparable between groups. In the control group, both Rawm and Rawe were significantly increased at T36-60, and Cdyn was significantly decreased at T36-60 compared with the baseline. Patients given alprostadil showed no change in Rawm, Rawe, or Cdyn at T36-60. Thus, IV alprostadil seems to have a bronchodilator effect in humans. IMPLICATIONS: IV alprostadil, an analog of prostaglandin E(1), prevents thiamylal-fentanyl-induced bronchoconstriction in humans. This finding suggests that IV alprostadil has a bronchodilator effect.

Intravenous colforsin daropate, a water-soluble forskolin derivative, prevents thiamylal-fentanyl-induced bronchoconstriction in humans.

OBJECTIVE: Forskolin, a direct activator of adenylate cyclase, can relax airway smooth muscle, similar to other agents that increase intracellular cyclic adenine monophosphate. However, the potential usefulness of forskolin in treating bronchospasm is limited by its poor water solubility. Colforsin daropate is a novel and potent water-soluble forskolin derivative. No clinical data have been published on the bronchorelaxant effects of this drug. The aim of this study was to investigate whether intravenous colforsin daropate prevents thiamylal-fentanyl-induced bronchoconstriction. DESIGN: Double-blind, prospective, placebo-controlled randomized study. SETTING: University teaching hospital. PATIENTS: Thirty-six patients were allocated randomly to two groups: the control group (n = 18) and colforsin daropate group (n = 18). INTERVENTIONS: Intravenous administration of colforsin daropate or placebo (normal saline). MEASUREMENTS AND MAIN RESULTS: Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.3 mg/kg. A 15 mg x kg(-1) x hr(-1) continuous infusion of thiamylal followed anesthetic induction. Controlled ventilation was maintained, delivering 50% nitrous oxide in oxygen. Twenty minutes after the induction of anesthesia, the control group patients started to receive 7.5 mL/hr continuous infusion of normal saline, and the colforsin daropate group patients started to receive 0.75 microg x kg(-1) x min(-1) (7.5 mL/hr) continuous infusion of colforsin daropate for 60 min. After that, both groups received fentanyl 5 microg/kg. Systolic and diastolic arterial pressure, heart rate, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured at the baseline, just before the administration of fentanyl (T30), at three consecutive 6-min intervals after fentanyl injection (T36, T42, and T48) and 30 min after fentanyl injection (T60). At baseline, both groups had comparable Rawm, Rawe, and Cdyn values. In the control group, Rawm increased significantly at T36-60 compared with the baseline, Rawe increased significantly at T36-48 compared with the baseline, and Cdyn decreased significantly at T36-60 compared with the baseline. In the colforsin daropate group, there were no changes in Rawm, Rawe or Cdyn at T36-60. CONCLUSIONS: These observations suggest that intravenous colforsin daropate has a bronchodilator effect in humans.

[Changes in ionized magnesium concentrations during general anesthesia].

The change in ionized magnesium (Mg) was investigated during isoflurane-nitrous oxide-oxygen anesthesia. The patients were divided into two groups by induction method of anesthesia. Group 1 was induced with thiamylal 4 mg.kg-1 and Group 2 was induced with ketamine 1 mg.kg-1. The ionized Mg concentration was recorded by NOVA 8 analyzer and observed during anesthesia. We also recorded the serum concentration of total Mg after administration of thiamylal. During induction of anesthesia and surgery, ionized Mg concentration decreased significantly in both groups. The ionized Mg concentration after administration of thiamylal was significantly lower than that after administration of ketamine. The serum total Mg concentration did not decrease throughout the anesthesia course. The ionized calcium concentration decreased, but the concentration of Na and K remained essentially unchanged. We conclude, therefore, that ionized Mg concentration decreases during surgery under general anesthesia, in part, possibly by the effect of anesthetic agent on the cell membrane itself.

Incidence of histamine release after the administration of midazolam-ketamine in allergic patients.

OBJECTIVE: We examined the effects of midazolam-ketamine which was used during the induction of anesthesia against histamine release, skin reactions and hemodynamic changes in patients with a history of allergy. SUBJECTS: Forty allergic patients and 40 non-allergic patients undergoing oral surgery were examined. METHODS: Midazolam ketamine was used for the induction of anesthesia in 40 patients with a history of allergy (M-K group) and thiamylal was used for the induction of anesthesia in 40 patients without any history of allergy (BARB group). Venous blood samples were obtained before induction as a control and 0.5, 1, 3, 5 minutes after the administration of each drug in order to measure the plasma histamine level. In addition, any observed hemodynamic changes were simultaneously recorded. The plasma histamine level was measured using the HPLC (high performance liquid chromatography) post-label system. RESULTS: The incidence of histamine release, skin reactions and hemodynamic changes were 37.5%, 10.0% and 7.5%, in the M-K group, and 40.0%, 12.5% and 12.5%, in the BARB group, respectively. Although the mean basal plasma histamine level in the M-K group (0.46 +/- 0.23 ng/ml) who had a history of allergy was much higher than that in the BARB group (0.28 +/- 0.17 ng/ml) (p < 0.001), the incidence of histamine release and clinical symptoms were similar between the two groups. CONCLUSIONS: The induction of anesthesia with midazolam-ketamine was thus found to be a valuable method for allergic patients, because the incidence of histamine release, skin reactions and hemodynamic changes in allergic patients were similar to those in non-allergic patients induced by thiamylal and no significant changes were observed in the plasma histamine level after the administration of midazolam-ketamine in spite of the high level of basal plasma histamine.

Effects of propofol anesthesia on cognitive recovery of patients undergoing electroconvulsive therapy.

The effects of different doses of propofol on post-electroconvulsive therapy (ECT) cognitive recovery were evaluated together with the effects on seizure duration and hemodynamic changes during ECT in 15 depressive patients. Propofol attenuated the increase in arterial blood pressure and heart rate in a dose-dependent manner compared with thiamylal. Propofol showed a clinically significant anticonvulsant effect during ECT in a dose-dependent manner. There were no significant differences among the four different induction groups in the mean recovery time from anesthesia, however, a low dose of propofol suppressed the early recovery of cognitive function. For early cognitive recovery after ECT, a deep anesthetic level is necessary when the traditional ECT apparatus is used which produces sine curve wave stimuli.

[A comparison of the incidence of postoperative nausea and vomiting after propofol-fentanyl anesthesia and that after nitrous oxide-isoflurane anesthesia].

We compared the incidence of postoperative nausea and vomiting after total intravenous propofol-fentanyl anesthesia (TIVA group) and that after thiamylal-nitrous oxide-isoflurane anesthesia (GOI group) in 60 ASA physical I and II patients for elective abdominal simple total hysterectomy. When the patients returned to the ward, the incidence of nausea was lower in TIVA group than in GOI group (P < 0.05), but no difference was found in the incidence of vomiting between the two groups. There were no differences in the incidence of nausea and vomiting 6 hours after the operation and on the next morning between the two groups. Postoperative pain scores were similar between the two groups, while total postoperative evaluation scores (nausea, vomiting, pain, fever, and sleep disturbance) were lower in TIVA group (P < 0.05). We conclude that TIVA with propofol-fentanyl reduced the incidence of nausea and improved total evaluation scores in the immediate postoperative period.

Unintentional epidural administration of thiamylal. Case report.

BACKGROUND AND OBJECTIVES: A 36-year-old woman was scheduled for surgery of bicornuate uterus under epidural anesthesia. METHODS: As a test dose, 3 mL 2.5% thiamylal was injected unintentionally through the epidural catheter instead of 1.5% lidocaine with 15 micrograms epinephrine. RESULTS: Immediately the patient complained of burning pain in the low back area. Administrations of 10 mL 2% lidocaine without epinephrine and 10 mL normal saline containing hydrocortisone 100 mg were performed through the epidural catheter. CONCLUSIONS: The patient recovered without permanent neurologic sequelae.