Effect of midazolam in autism spectrum disorder: A retrospective observational analysis.

BACKGROUND: While midazolam is commonly used as premedication for uncooperative patients, its effects are difficult to predict in patients with autism spectrum disorder for whom abnormalities in gamma-aminobutyric acid have been reported. This study aimed to investigate the influence of autism spectrum disorder on the effect of midazolam when used as premedication. METHODS: This retrospective observational study was performed between April 2017 and August 2018. Before inducing general anesthesia with sevoflurane for dental treatment, 390 uncooperative patients received premedication with midazolam. Ordinal logistic regression analysis was performed with the Observer's Assessment of Alertness/Sedation score 30 min after premedication as the objective variable. Age, sex, American Society of Anesthesiologists physical status class, premedication route, dose per body weight, presence of specific disorders (autism spectrum disorder, intellectual disability, epilepsy, cerebral palsy, and other psychiatric disorders), and regular benzodiazepine or non-benzodiazepine psychotropic administration were included as explanatory variables. Kendall's rank correlation coefficient was used to assess the correlation between the Observer's Assessment of Alertness/Sedation score and cooperation level (1, obvious negative response; 2, negative response; 3, positive reaction; 4, obvious positive reaction) during admission and inhalation induction. All data were extracted from anesthesia and medical records. RESULTS: Age (odds ratio 1.437 [95% confidence interval (CI) 1.213-1.708], P < .001), autism spectrum disorder (1.318 [1.079-1.612], P = .007), benzodiazepine medication (0.574 [0.396-0.827], P = .002), and intramuscular route (1.478 [1.137-1.924], P = .004) were significantly associated with the Observer's Assessment of Alertness/Sedation score, while the score was negatively associated with cooperation levels during admission (τ = -0.714, P < .001) and inhalation induction (τ = -0.606, P < .001). CONCLUSIONS: Patients with autism spectrum disorder may be susceptible to premedication with midazolam; however, regular benzodiazepine administration may reduce the effect.

Swallowing ability and intra-oral water-retaining ability during moderate propofol sedation in healthy human volunteers: A prospective observational study.

BACKGROUND: The cough reflex or aspiration under monitored anaesthesia care might be associated with sedative-induced changes in swallowing and intra-oral water-retaining abilities. OBJECTIVES: To investigate the effects of moderate propofol sedation on swallowing and intra-oral water-retaining ability. DESIGN: Prospective observational study. SETTING: Single tertiary care centre during 2017. PARTICIPANTS: A total of 13 healthy adult volunteers. INTERVENTION: Volunteers in the supine position were asked to retain 10 ml of orally injected water for 5 min. After 5 minutes or when the water was spontaneously swallowed, the retention time and residual intra-oral water volume were measured. Subjects then voluntarily swallowed a further 10 ml of injected water and the residual water volume was measured. This whole process was repeated under sedation with propofol at effect-site concentrations of 0.5, 1.0 and 1.5 µg ml-1. MAIN OUTCOME MEASURES: The primary outcome was the estimated volume swallowed (swallowing volume); the secondary outcome was water retention time. RESULTS: Median water retention time decreased from 300 to 11 s (P < 0.001), and greater spontaneous swallowing was induced with increased propofol effect-site concentrations measuring up to 1.5 µg ml-1 (P < 0.001). The median of the estimated swallowing volumes with voluntary swallowing while awake and with all three concentrations of propofol were 9.5, 9.6, 9.6 and 9.4 ml, respectively (P = 0.805); more water remained after spontaneous swallowing than after voluntary swallowing at all concentrations. Differences in mean estimated swallowing volumes between voluntary and spontaneous swallowing were 3.4 ml (95% CI, 0.9 to 6.0, P = 0.016) for 0.5 µg ml-1, 4.1 ml (95% CI, 1.8 to 6.3, P = 0.002) for 1.0 µg ml-1 and 5.1 ml (95% CI, 3.4 to 6.8, P < 0.001) for 1.5 µg ml-1. CONCLUSIONS: Moderate propofol sedation decreases water-retaining ability but has no effect on voluntary swallowing. Ensuring that patients can respond under sedation may effectively prevent the unexpected cough reflex and aspiration by enabling occasional voluntary swallowing. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000027517.

Dexmedetomidine and Midazolam Sedation Reduces Unexpected Patient Movement During Dental Surgery Compared With Propofol and Midazolam Sedation.

PURPOSE: Owing to its unpredictability, unexpected patient movement is one of the most important problems during surgery while under monitored anesthesia care with sedation. The purpose of this study was to compare unexpected patient movement during dental surgery while under dexmedetomidine and propofol sedation. MATERIALS AND METHODS: The authors designed and implemented a prospective randomized controlled trial. Patients undergoing dental surgery requiring intravenous sedation were randomly assigned to dexmedetomidine and midazolam (dexmedetomidine group) or propofol and midazolam (propofol group) sedation. In each group, midazolam 0.02 mg/kg was administered in conjunction with continuous administration of dexmedetomidine or propofol to maintain a bispectral index value of 70 to 80. Unexpected patient movement interfering with the procedure was defined as acceptable, defined as no body movement or only 1 controllable movement, or unacceptable, defined as at least 2 controllable movements or any uncontrollable movement. The primary outcome was unexpected patient movement, and the secondary outcome was defined as snoring and cough reflex. Other variables included demographic and procedural characteristics. Continuous or ordinal variables were analyzed using the Student t test or Mann-Whitney test. Dichotomous or categorical variables were analyzed using the χ2 test or Fisher exact test. A P value less than.05 was considered statistically significant. RESULTS: Eighty-eight patients were enrolled in the study (dexmedetomidine group, n = 44; propofol group, n = 44). There were no relevant differences between groups for demographics and baseline variables. Intraoperative unacceptable patient movement occurred more commonly in the propofol group (n = 13; 30%) than in the dexmedetomidine group (n = 4; 9%; P = .015). Intraoperative snoring occurred more commonly in the dexmedetomidine than in the propofol group (P = .045). Incidence and number of cough reflexes were comparable between groups. CONCLUSION: Dexmedetomidine and midazolam sedation decreases unexpected patient movement during dental surgery compared with propofol and midazolam sedation.

Frequency characteristics of pressure transducer kits with inserted pressure-resistant extension tubes.

The accurate monitoring of arterial blood pressure is important for cardiovascular management. However, the frequency characteristics of pressure transducer kits are influenced by the length of the pressure-resistant tube. To date, there have been few studies addressing the frequency characteristics of pressure transducer kits with inserted pressure-resistant extension tubes (pressure-resistant extension tube (ET) circuits). In this study, we examine ET circuits from the viewpoint of the frequency characteristics of pressure transducer kits. DT4812J transducer kits (length 150 cm; Argon Medical Devices, TX, USA) were used. Three original ET circuits were prepared, with the pressure-resistant tube of the DT4812J being extended with a 30-cm length of pressure-resistant tube (180ET circuit), a 60-cm length of pressure-resistant tube (210ET circuit), and a 90-cm length of pressure-resistant tube (240ET circuit). Each of these circuits was evaluated as part of this study. The natural frequency of the original DT4812J circuit was 45.90 Hz while the damping coefficient was 0.160. For the 180 ET circuit, the natural frequency and damping coefficient were 36.4 Hz and 0.162, respectively. For the ET210 circuit, the natural frequency and damping coefficient were 30.3 Hz and 0.175, respectively. For the ET210 circuit, the natural frequency and damping coefficient were 25.3 Hz and 0.180, respectively. As a result of extending the circuit, it was found that the natural frequency decreased drastically, while the damping coefficient increased slightly. When the extension of a pressure transducer kit is required, we should pay careful attention to the major decrease in the natural frequency, which may influence the pressure monitoring.

Effect of using a Planecta™ port with a three-way stopcock on the natural frequency of blood pressure transducer kits.

Blood pressure transducer kits are equipped with two types of Planecta™ ports-the flat-type Planecta™ port (FTP) and the Planecta™ port with a three-way stopcock (PTS). We reported that FTP application decreased the natural frequency of the kits. However, Planecta™ is an invaluable tool as it prevents infection, ensures technical simplicity, and excludes air. Hence, an ideal Planecta™ port that does not decrease the frequency characteristics is required. As a first step in this direction, we aimed to assess the influence of PTSs on the natural frequency of blood transducer kits. A DTXplus transducer kit (DT4812J; Argon Medical Devices, TX, USA) was used along with ≥1 PTSs (JMS, Hiroshima, Japan), and the frequency characteristics were assessed. The natural frequency and damping coefficient of each kit were obtained by using frequency characteristics analysis software, and these parameters were evaluated by plotting them on Gardner's chart. Regardless of whether one or two PTSs were inserted, the natural frequency of the kits only slightly decreased (from 42.5 to 41.1 Hz, when 2 PTSs were used). Thus, the frequency characteristics of the kits with PTSs were adequate for pressure monitoring. The insertion of ≥2 FTPs in pressure transducer kits should be avoided, as they markedly decrease the natural frequency and lead to underdamping. However, the effect of PTS insertion in pressure transducer kits on the frequency characteristics is minimal. Thus, we found that the use of PTS markedly improved the frequency characteristics as compared to the use of FTP.

A prospective, randomized controlled trial of conscious sedation using propofol combined with inhaled nitrous oxide for dental treatment.

PURPOSE: Adverse reactions during propofol sedation include a decrease in arterial blood pressure, propofol-induced pain on injection, and airway complications. The purpose of this study was to investigate whether combined use of intravenous propofol and inhaled nitrous oxide could decrease the hypotensive and other adverse effects of propofol. PATIENTS AND METHODS: We designed and implemented a prospective, randomized controlled trial. Patients undergoing dental procedures requiring intravenous sedation were randomly allocated to 2 groups: group P comprised those receiving sedation with propofol alone, and group N+P comprised those receiving sedation with 40% nitrous oxide inhalation and propofol. During the dental procedures, the sedation level was maintained at an Observer's Assessment of Alertness/Sedation scale score of 4 by adjusting propofol's target plasma concentration. Nitrous oxide inhalation was the predictor variable, whereas the hemodynamic changes, amount and concentration of propofol, and adverse events were the outcome variables. RESULTS: Eighty-eight patients were successfully analyzed without any complications. The total amount of propofol was significantly less in group N+P (249.8 ± 121.7 mg) than in group P (310.3 ± 122.4 mg) (P = .022), and the mean concentration of propofol was significantly less in group N+P (1.81 ± 0.34 µg/mL) than in group P (2.05 ± 0.44 µg/mL) (P = .006). The mean blood pressure reduction in group N+P (11.0 ± 8.0 mm Hg) was significantly smaller than that in group P (15.8 ± 10.2 mm Hg) (P = .034). Pain associated with the propofol injection and memory of the procedure were less in group N+P (P = .011 and P = .048, respectively). Nitrous oxide did not affect respiratory conditions or recovery characteristics. CONCLUSIONS: The results of this study suggest that nitrous oxide inhalation combined with propofol sedation attenuates the hypotensive effect and pain associated with propofol injections, along with potentiating the amnesic effect.

Initial loading of dexmedetomidine and continuous propofol sedation for prevention of delayed recovery: A randomized controlled trial.

BACKGROUND: Sedation with continuous dexmedetomidine and bolus midazolam administration provides a lower incidence of unacceptable patient movement during procedures but requires a longer recovery time. The authors aimed to compare recovery time and unacceptable patient movement during sedation with initial loading of dexmedetomidine followed by continuous propofol infusion with those during sedation with continuous dexmedetomidine and bolus midazolam administration. METHODS: In this prospective randomized controlled trial, 54 patients undergoing dental surgery and requiring intravenous sedation were assigned to either the dexmedetomidine and propofol group (n = 27, dexmedetomidine administered at 6 µg/kg/h for 5 minutes, followed by continuous propofol infusion using a target-controlled infusion) or the dexmedetomidine and midazolam group (n = 27, dexmedetomidine administered at 0.2-0.7 µg/kg/h continuously after the same initial loading dose with bolus midazolam). A bispectral index of 70 through 80 was maintained during the procedure. Patient movement that interfered with the procedure and time from the end of sedation to achieving a negative Romberg sign were assessed. RESULTS: Times from the end of sedation to achieving a negative Romberg sign in the dexmedetomidine and propofol group (median, 14 minutes [interquartile range, 12-15 minutes]) were significantly shorter (P < .001) than in the dexmedetomidine and midazolam group (median, 22 minutes [interquartile range, 17.5-30.5 minutes]). The incidence of unacceptable patient movement was comparable between groups (n = 3 in the dexmedetomidine and propofol group, n = 4 in the dexmedetomidine and midazolam group; P = .999). CONCLUSIONS: Sedation with a single loading dose of dexmedetomidine followed by continuous propofol infusion can prevent delayed recovery without increasing unacceptable patient movement. PRACTICAL IMPLICATIONS: The combination of dexmedetomidine and propofol may provide high-quality sedation for ambulatory dental practice. This clinical trial was registered in the University Hospital Medical Information Network Clinical Trials Registry. The registration number is UMIN000039668.

Polysomnographic analysis of respiratory events during sleep in young nonobese Japanese adults without clinical complaints of sleep apnea.

STUDY OBJECTIVES: The present study aimed to investigate the occurrence and characteristics of apnea-hypopnea events in young nonobese healthy Japanese participants. METHODS: One hundred and three young adult participants without sleep complaints (men: 56; women: 47; age: 24.5 ± 3.0 years; body mass index: 20.9 ± 1.8 kg/m²) underwent 2-night polysomnography. Data on the 2nd night were scored according to American Academy of Sleep Medicine criteria version 2.1. The apnea-hypopnea index (AHI) was estimated. The arousal threshold was calculated in participants with AHI ≥ 5 events/h. Apnea-hypopnea events were rescored by 3 other criteria issued by the American Academy of Sleep Medicine (AASM): Chicago criteria in 1999 and recommended and alternative criteria in 2007. RESULTS: Participants had good sleep characterized by high sleep efficiency (93.2%). Mean AHI of AASM 2.1 recommended criteria was 4.0 ± 5.3 events/h. AHI was significantly higher in men (median [range] = 4.0[.3-35.8] events/h) than in women (1.6 [.1-18.1] events/h). The prevalence rates of AHI ≥ 5 events/h and ≥ 15 events/h were 25.2 and 3.9%, respectively. The arousal threshold was estimated as -7.7 ± 2.6 cm H2O. AHI was lower for AASM 2007 recommended criteria (.8 [.0-18.2 events/h]) and AASM 2007 alternative (2.0 [.1-32.2] events/h) than for AASM version 2.1 recommended criteria (2.4 [.1-32.9] events/h) and AASM Chicago (4.6 [.1-35.8] events/h). The percentage of participants with AHI ≥ 5 events/h was approximately 2-fold higher with AASM Chicago (44.6%) than with AASM version 2.1 recommended criteria. CONCLUSIONS: The present study demonstrated that 25% of young nonobese Japanese participants had subclinical obstructive sleep apnea. The presence of frequent airflow limitations may be a risk factor for the development of obstructive sleep apnea in Japanese individuals.

Mandibular advancement impairs swallowing ability more than head extension but less than mouth opening in the supine position.

Mandibular advancement in the supine position may influence swallowing during dental treatment under intravenous sedation. This study investigated the influence of mandibular advancement in the supine position on swallowing ability, compared with head extension and mouth opening. The water swallowing test was performed in 13 healthy, awake, supine, adult subjects under four head and mandibular positions. An electromyogram of the suprahyoid muscles was recorded; the duration and peak amplitude were examined. A greater volume of water remained in the mouth during mouth opening and mandibular advancement relative to the neutral position; the volume in the mandibular advancement position was larger and smaller than that in the head extension position and during mouth opening, respectively. The duration of the electromyogram in the head extension position was longer than that in the mandibular advancement position, without differences in the amplitude. Thus, swallowing ability in the supine position was more impaired with mandibular advancement, relative to neutral and head extension positions, but less than that observed with mouth opening. Although unconfirmed by electromyogram, our findings suggest that head extension might improve airway patency by reducing the impairment of swallowing ability compared with mandibular advancement.

Anaphylaxis with delayed appearance of skin manifestations during general anesthesia: two case reports.

BACKGROUND: Anaphylaxis is difficult to diagnose in the absence of skin or mucosal signs and symptoms. We report two cases of anaphylaxis under general anesthesia, in which the initial presentation was in the form of respiratory signs, followed by skin manifestations 10-15 min later. Diagnosis of anaphylaxis was delayed because skin symptoms were absent early on in the presentation. CASE PRESENTATION: In the first case, a 23-year-old male patient with jaw deformity was scheduled to undergo maxillary alveolar osteotomy. After intubation, auscultation indicated a sudden decrease in breath sounds, together with severe hypotension. Approximately 10 min later, flushing of the skin and urticaria on the thigh appeared and spread widely throughout the body. In the second case, a 21-year-old female patient with jaw deformity was scheduled to undergo maxillomandibular osteotomy. Twenty minutes after the start of dextran infusion, her lungs suddenly became difficult to ventilate, and oxygen saturation decreased to 90%. Approximately 15 min later, flushing of the skin and urticaria were observed. CONCLUSION: In both cases, there was a time lag between the appearance of respiratory and skin symptoms, which resulted in a delay in the diagnosis, and hence, treatment of anaphylaxis. Our experience highlights the fact that it is difficult to diagnose anaphylaxis under general anesthesia.

Airway management for glossopexy in infants with micrognathia and obstructive breathing.

STUDY OBJECTIVES: To identify airway management and tracheal intubation techniques for glossopexy in infants with preexisting airway obstruction under general anesthesia. DESIGN: Retrospective, observational study. SETTINGS: Operating room of a university hospital between January 2003 and March 2015. All operations were performed by oral and maxillofacial surgeons. PATIENTS: Thirteen patients who received general anesthesia for glossopexy and reversal after 7 months. MEASUREMENTS: The medical records of these infants were retrospectively examined to evaluate the following: age, sex, height and weight at surgery, preoperative airway status, tracheal intubation route (oral or nasal), method for inducing general anesthesia, method for establishing the airway during mask ventilation, apparatus used for tracheal intubation, Cormack-Lehane classification when using a Macintosh laryngoscope and video laryngoscope, and the need for airway placement after extubation. RESULTS: Prone positioning and/or an airway of some kind before surgery were required in 38.5% of infants needing glossopexy. Difficult mask ventilation was common, occurring in 50% of the patients, and the incidence of airway placement during mask ventilation was significantly higher in infants with preoperative complete or incomplete obstruction (100%) than in infants with snoring (25%). Of these high-risk infants, 25% could not be intubated with a direct laryngoscope or Glidescope Cobalt and required fiberoptic intubation. CONCLUSION: There are severe cases of infants with difficult mask ventilation and difficult tracheal intubation in which a fiberscope is required because video laryngoscopy fails to improve the view of the larynx.

Tooth extraction in patients taking nonvitamin K antagonist oral anticoagulants.

BACKGROUND/PURPOSE: The nonvitamin K antagonist oral anticoagulants direct-thrombin inhibitor dabigatran and the Xa inhibitors rivaroxaban and apixaban are now being used clinically. The course of the patients on these anticoagulants who underwent tooth extraction was assessed. MATERIALS AND METHODS: The medical charts of these patients were investigated. Tooth extraction was performed while maintaining conventional anticoagulant therapy. RESULTS: Twenty-three teeth were extracted in 19 patients, including two surgical extractions. Among the 19 patients, nine patients ingested rivaroxaban, six apixaban, and four dabigatran. One patient on rivaroxaban showed persistent postoperative bleeding following two surgical extractions. Mild oozing was observed in five patients (two on rivaroxaban and three on apixaban). There was no bleeding episode in the patients on dabigatran. CONCLUSION: The patients on rivaroxaban with a prolonged prothrombin time value have a higher risk of bleeding, especially undergoing surgical extraction. Apixaban correlates to neither activated partial thromboplastin time nor prothrombin time values and the countermeasures should be employed based on the clinical findings.

Haemostatic management for oral surgery in patients supported with left ventricular assist device--a preliminary retrospective study.

We investigated haemostatic management, frequency of postoperative bleeding, and prognosis of patients who had left ventricular assist devices, and who were having oral surgical procedures between April 2002 and March 2014, to identify risk factors for bleeding and find out which were the best methods of haemostasis. Medical records were examined retrospectively and we recorded details of the patients, and frequency of bleeding together with factors associated with it. Twenty-nine patients had 39 oral operations, and there were 17 bleeds (44%). The first procedure for each patient was used for statistical calculations. Duration of bleeding tended to be longer for patients with implantable devices (median (interquartile range, IQR) 12.0 (3-18) days) than for those with extracorporeal devices (median (IQR) 3.0 (1-4) days; p=0.079). There was a significantly greater difference in prothrombin time-international normalised ratio (PT-INR) before and after operation in patients who bled, whose median (range) was 0.85 (0.2-1.81), than in those who did not (median (IQR) 0.16 (-0.09-0.31) (p=0.015). There were moderate correlations with postoperative bleeding were seen for the difference between preoperative and postoperative PT-INR (r=0.479, p=0.012) and PT-INR value when bleeding (r=0.407, p=0.035). In conclusion, postoperative bleeding occurred after oral operations in 17/29 patients with left ventricular assist devices by a median (IQR) of 0.85 (0.2-1.81) of the preoperative value.

The effect of nitrous oxide inhalation on the hypotensive response to propofol: a randomized controlled trial.

OBJECTIVE: Decrease in arterial blood pressure is a prominent adverse reaction during propofol (Disoprivan; AstraZeneca K.K., Osaka, Japan) sedation. The purpose of this prospective randomized study was to explore the effects of nitrous oxide (N2O) on the hypotensive response during propofol sedation. STUDY DESIGN: Twenty-six healthy volunteers received intravenous sedation with propofol alone (group P, n=13) or a combined technique using 20% N2O and propofol (group N+P, n=13). Propofol was administered by a target-controlled infusion system to attain and maintain a plasma propofol concentration of 1.5µg/mL. Hemodynamic and autonomic parameters were measured. RESULTS: Mean arterial pressure decreased in both groups, the hypotensive response in group N+P being significantly smaller than in group P. Reduction in the low-frequency power of systolic blood pressure variability, indicative of sympathetic nervous activity, was also smaller in group N+P than in group P. CONCLUSIONS: Addition of N2O to propofol sedation can attenuate the hypotensive effect of propofol.

Arteriosclerosis can predict hypotension during anesthesia induction in patients 40 years and older.

STUDY OBJECTIVES: To identify the factors that predict blood pressure (BP) changes during induction of general anesthesia, and the relationship between the level of arteriosclerosis and BP changes during anesthesia induction. DESIGN: Prospective, case-control observational study. SETTINGS: Operating room of a university hospital. PATIENTS: Seventy-two patients who received general anesthesia for oral and maxillofacial surgery. MEASUREMENTS: Brachial-ankle pulse wave velocity (baPWV) and central BP were measured. The primary variable was the parameters affecting BP changes during the induction of general anesthesia. For additional analyses, the parameters were compared between high and low PWV groups (1606 cm/s was the cutoff value of baPWV). To measure the relationships between the parameters and BP changes, bivariate and multiple linear regression analyses were performed. RESULTS: Seventy-two patients (including 41 men) with a mean age of 61.7 years and a median baPWV value of 1606 cm/s were evaluated. Significantly higher values for age, central BP, preoperative systolic BP (SBP), amount of decrease in SBP and diastolic BP, and number of patients with diabetes mellitus (DM) and hypertension were observed in the high PWV group. Multiple linear regression analysis demonstrated that age, baPWV, and DM were factors independently associated with the amount of decrease in SBP. CONCLUSION: In patients 40 years and older, age, baPWV, and DM are thought to be effective predictors of the amount of decrease in SBP during induction of general anesthesia.