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1.  Comparison of recovery of propofol and methohexital sedation using an infusion pump. 
Anesthesia Progress  1996;43(1):9-13.
Two sedative anesthetic agents administered by an infusion pump were compared during third molar surgery. Forty American Society of Anesthesiologists (ASA) class I or II volunteers were randomly allocated to two groups. All subjects received supplemental oxygen via a nasal hood, fentanyl (0.0007 mg/kg intravenous [i.v.] bolus), and midazolam (1 mg/2 min) titrated to effect. Patients then received either 0.3 mg/kg of methohexital or 0.5 mg/kg of propofol via an infusion pump. Upon completion of the bolus, a continuous infusion of 0.05 mg/kg/min methohexital or 0.066 mg/kg/min propofol was administered throughout the procedure. Hemo-dynamic and respiratory parameters and psychomotor performance were compared for the two groups and no significant differences were found. The continuous infusion method maintained a steady level of sedation. Patients receiving propofol had a smoother sedation as judged by the surgeon and anesthetist.
PMCID: PMC2153445  PMID: 10323119
2.  Comparison between the recovery time of alfentanil and fentanyl in balanced propofol sedation for gastrointestinal and colonoscopy: a prospective, randomized study 
BMC Gastroenterology  2012;12:164.
Background
There is increasing interest in balanced propofol sedation (BPS) titrated to moderate sedation (conscious sedation) for endoscopic procedures. However, few controlled studies on BPS targeted to deep sedation for diagnostic endoscopy were found. Alfentanil, a rapid and short-acting synthetic analog of fentanyl, appears to offer clinically significant advantages over fentanyl during outpatient anesthesia.
It is reasonable to hypothesize that low dose of alfentanil used in BPS might also result in more rapid recovery as compared with fentanyl.
Methods
A prospective, randomized and double-blinded clinical trial of alfentanil, midazolam and propofol versus fentanyl, midazolam and propofol in 272 outpatients undergoing diagnostic esophagogastroduodenal endoscopy (EGD) and colonoscopy for health examination were enrolled. Randomization was achieved by using the computer-generated random sequence. Each combination regimen was titrated to deep sedation. The recovery time, patient satisfaction, safety and the efficacy and cost benefit between groups were compared.
Results
260 participants were analyzed, 129 in alfentanil group and 131 in fentanyl group. There is no significant difference in sex, age, body weight, BMI and ASA distribution between two groups. Also, there is no significant difference in recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between two groups. Though deep sedation was targeted, all cardiopulmonary complications were minor and transient (10.8%, 28/260). No serious adverse events including the use of flumazenil, assisted ventilation, permanent injury or death, and temporary or permanent interruption of procedure were found in both groups. However, fentanyl is New Taiwan Dollar (NT$) 103 (approximate US$ 4) cheaper than alfentanil, leading to a significant difference in total cost between two groups.
Conclusions
This randomized, double-blinded clinical trial showed that there is no significant difference in the recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between the two most common sedation regimens for EGD and colonoscopy in our hospital. However, fentanyl is NT$103 (US$ 4) cheaper than alfentanil in each case.
Trial registration
Institutional Review Board of Buddhist Tzu Chi General Hospital (IRB097-18) and Chinese Clinical Trial Registry (ChiCTR-TRC-12002575)
doi:10.1186/1471-230X-12-164
PMCID: PMC3607964  PMID: 23170921
Balanced propofol sedation; Alfentanil; Fentanyl; Deep sedation; Diagnostic endoscopy; Cost benefit
3.  Deep sedation during gastrointestinal endoscopy: Propofol-fentanyl and midazolam-fentanyl regimens 
AIM: To compare deep sedation with propofol-fentanyl and midazolam-fentanyl regimens during upper gastrointestinal endoscopy.
METHODS: After obtaining approval of the research ethics committee and informed consent, 200 patients were evaluated and referred for upper gastrointestinal endoscopy. Patients were randomized to receive propofol-fentanyl or midazolam-fentanyl (n = 100/group). We assessed the level of sedation using the observer’s assessment of alertness/sedation (OAA/S) score and bispectral index (BIS). We evaluated patient and physician satisfaction, as well as the recovery time and complication rates. The statistical analysis was performed using SPSS statistical software and included the Mann-Whitney test, χ2 test, measurement of analysis of variance, and the κ statistic.
RESULTS: The times to induction of sedation, recovery, and discharge were shorter in the propofol-fentanyl group than the midazolam-fentanyl group. According to the OAA/S score, deep sedation events occurred in 25% of the propofol-fentanyl group and 11% of the midazolam-fentanyl group (P = 0.014). Additionally, deep sedation events occurred in 19% of the propofol-fentanyl group and 7% of the midazolam-fentanyl group according to the BIS scale (P = 0.039). There was good concordance between the OAA/S score and BIS for both groups (κ = 0.71 and κ = 0.63, respectively). Oxygen supplementation was required in 42% of the propofol-fentanyl group and 26% of the midazolam-fentanyl group (P = 0.025). The mean time to recovery was 28.82 and 44.13 min in the propofol-fentanyl and midazolam-fentanyl groups, respectively (P < 0.001). There were no severe complications in either group. Although patients were equally satisfied with both drug combinations, physicians were more satisfied with the propofol-fentanyl combination.
CONCLUSION: Deep sedation occurred with propofol-fentanyl and midazolam-fentanyl, but was more frequent in the former. Recovery was faster in the propofol-fentanyl group.
doi:10.3748/wjg.v19.i22.3439
PMCID: PMC3683682  PMID: 23801836
Endoscopy; Deep sedation; Anesthetic administration; Anesthetic dose; Adverse effects
4.  Comparison of Propofol-Remifentanil Versus Propofol-Ketamine Deep Sedation for Third Molar Surgery 
Anesthesia Progress  2012;59(3):107-117.
This study aimed to compare continuous intravenous infusion combinations of propofol-remifentanil and propofol-ketamine for deep sedation for surgical extraction of all 4 third molars. In a prospective, randomized, double-blinded controlled study, participants received 1 of 2 sedative combinations for deep sedation for the surgery. Both groups initially received midazolam 0.03 mg/kg for baseline sedation. The control group then received a combination of propofol-remifentanil in a ratio of 10 mg propofol to 5 μg of remifentanil per milliliter, and the experimental group received a combination of propofol-ketamine in a ratio of 10 mg of propofol to 2.5 mg of ketamine per milliliter; both were given at an initial propofol infusion rate of 100 μg/kg/min. Each group received an induction loading bolus of 500 μg/kg of the assigned propofol combination along with the appropriate continuous infusion combination . Measured outcomes included emergence and recovery times, various sedation parameters, hemodynamic and respiratory stability, patient and surgeon satisfaction, postoperative course, and associated drug costs. Thirty-seven participants were enrolled in the study. Both groups demonstrated similar sedation parameters and hemodynamic and respiratory stability; however, the ketamine group had prolonged emergence (13.6 ± 6.6 versus 7.1 ± 3.7 minutes, P = .0009) and recovery (42.9 ± 18.7 versus 24.7 ± 7.6 minutes, P = .0004) times. The prolonged recovery profile of continuously infused propofol-ketamine may limit its effectiveness as an alternative to propofol-remifentanil for deep sedation for third molar extraction and perhaps other short oral surgical procedures, especially in the ambulatory dental setting.
doi:10.2344/12-00001.1
PMCID: PMC3468288  PMID: 23050750
Propofol; Ketamine; Remifentanil; Deep sedation; TIVA
5.  A Randomized Double-Blind Pilot Study to Compare Conscious Sedation Produced by Diazepam Against Sufentanil 
Anesthesia Progress  1987;34(4):137-141.
Intravenous sufentanil, an analog of fentanyl, was compared to diazepam for conscious sedation in ambulatory dental outpatients. Ten patients undergoing the surgical removal of impacted third molars served as subjects in a double-blind, within-subject, single crossover study. Sedation was achieved with a combination of 30% nitrous oxide/70% oxygen by nasal mask and either diazepam (0.05—0.15 mg/kg) or sufentanic (0.05—0.15 μg/kg) titrated to a clinical endpoint of altered speech and relaxation. Intraoperative physiologic monitoring, patients' and the oral surgeon's subjective estimates of efficacy and psychomotor recovery were used to compare the two treatments. Both patients (eight of 10) and surgeons (six of 10) preferred sufentanil sedation. No significant differences were noted between treatments for psychomotor recovery. These preliminary data in a small sample suggest that sufentanil produces adequate conscious sedation in dental outpatients and should be evaluated further with larger patient samples.
PMCID: PMC2186288  PMID: 2964215
6.  Effect of sevoflurane versus propofol-based anesthesia on the hemodynamic response and recovery characteristics in patients undergoing microlaryngeal surgery 
Saudi Journal of Anaesthesia  2012;6(4):380-384.
Background:
This randomized study was conducted to compare the hemodynamic changes and emergence characteristics of sevoflurane versus propofol anesthesia for microlaryngeal surgery.
Methods:
Forty adult patients undergoing microlaryngoscopy were randomly allocated into two groups. In propofol group, anesthesia was induced with 2-3 mg/kg propofol and maintained with propofol infusion 50-200 μg/kg/h. In sevoflurane group induction was carried out with 5-8% sevoflurane and maintained with sevoflurane in nitrous oxide and oxygen. The propofol and sevoflurane concentrations were adjusted to maintain the bispectral index of 40-60. All patients received fentanyl 2 μg/kg before induction and succinylcholine 2 mg/kg to facilitate tracheal intubation. The hemodynamic changes during induction and suspension laryngoscopy were compared. In addition, the emergence time, time to extubation, and recovery were assessed.
Results:
The changes in heart rate were comparable. The mean arterial pressure was significantly lower after induction and higher at insertion of operating laryngoscope in propofol group as compared to sevoflurane group. More patients in propofol group had episodes of hypotension and hypertension than sevoflurane group. The emergence time, extubation times, and recovery time were similar in both groups.
Conclusion:
We found that sevoflurane showed advantage over propofol in respect of intraoperative cardiovascular stability without increasing recovery time.
doi:10.4103/1658-354X.105876
PMCID: PMC3591559  PMID: 23493938
General anesthesia; hemodynamic changes; microlaryngeal surgery; propofol; recovery; sevoflurane
7.  The effect of a subhypnotic dose of propofol for the prevention of coughing in adults during emergence from anesthesia with sevoflurane and remifentanil 
Korean Journal of Anesthesiology  2014;66(2):120-126.
Background
Coughing during emergence from general anesthesia may be detrimental. Propofol is known to inhibit airway reflexes. We evaluated the incidence and severity of coughing in adults who received a subhypnotic dose of propofol at the end of sevoflurane-remifentanil anesthesia.
Methods
Sixty patients, aged 18-65 years, undergoing elective nasal surgery under general anesthesia using sevoflurane and remifentanil were randomly allocated to the propofol group (n = 30) or the control group (n = 30). At the end of surgery, sevoflurane and remifentanil infusion was stopped. After 3 min, the propofol group received propofol 0.3 mg/kg and the control group received normal saline 0.03 ml/kg. The incidence and severity of cough, recovery time and hemodynamic parameters were evaluated during the emergence period.
Results
During emergence, the propofol group had the significantly lower incidence (60 vs. 87%) and severity of coughing compared with the control group (P = 0.04, P = 0.02, respectively). There were no significant differences in mean arterial pressure, heart rate, and recovery time during emergence between the two groups.
Conclusions
During emergence from sevoflurane-remifentanil anesthesia, a subhypnotic dose (0.3 mg/kg) of propofol decreases the incidence and severity of coughing without delaying wake up in adults undergoing nasal surgery.
doi:10.4097/kjae.2014.66.2.120
PMCID: PMC3948438  PMID: 24624269
Cough; Emergence; Propofol
8.  Clinical Effectiveness of an Anesthesiologist-Administered Intravenous Sedation Outside of the Main Operating Room for Pediatric Upper Gastrointestinal Endoscopy in Thailand 
Objectives. To review our sedation practice and to evaluate the clinical effectiveness of an anesthesiologist-administered intravenous sedation outside of the main operating room for pediatric upper gastrointestinal endoscopy (UGIE) in Thailand. Subjects and Methods. We undertook a retrospective review of the sedation service records of pediatric patients who underwent UGIE. All endoscopies were performed by a pediatric gastroenterologist. All sedation was administered by staff anesthesiologist or anesthetic personnel. Results. A total of 168 patients (94 boys and 74 girls), with age from 4 months to 12 years, underwent 176 UGIE procedures. Of these, 142 UGIE procedures were performed with intravenous sedation (IVS). The mean sedation time was 23.2 ± 10.0 minutes. Propofol was the most common sedative drugs used. Mean dose of propofol, midazolam and fentanyl was 10.0 ± 7.5 mg/kg/hr, 0.2 ± 0.2 mg/kg/hr, and 2.5 ± 1.2 mcg/kg/hr, respectively. Complications relatively occurred frequently. All sedations were successful. However, two patients became more deeply than intended and required unplanned endotracheal intubation. Conclusion. The study shows the clinical effectiveness of an anesthesiologist-administered IVS outside of the main operating room for pediatric UGIE in Thailand. All complications are relatively high. We recommend the use of more sensitive equipments such as end tidal CO2 and carefully select more appropriate patients.
doi:10.1155/2010/748564
PMCID: PMC2929513  PMID: 20811603
9.  Preanesthetic dexmedetomidine 1 µg/kg single infusion is a simple, easy, and economic adjuvant for general anesthesia 
Korean Journal of Anesthesiology  2013;65(2):114-120.
Background
Dexmedetomidine is an α2-adrenoreceptor agonist with sedative, analgesic and anxiolytic effects, and it has more selective α2-adrenergic effect than clonidine. We evaluate the effect of preansethetic dexmedetomidine 1 µg/kg single infusion on sedation, hemodynamics, anesthetic consumption, and recovery profiles during anesthesia.
Methods
Forty-two female patients with American Society of Anesthesiologists physical status I or II undergoing gynecologic surgery with anticipated operation time of 2 h, were randomly assigned to receive dexmedetomidine 1 µg/kg (Dex group) or saline (control group) iv over 10 min before anesthetic induction. After tracheal intubation with propofol 2 mg/kg, cisatracurium 0.15 mg/kg iv, anesthesia was maintained with sevoflurane, O2 50%, N2O 50% around a BIS value of 40.
Results
After study drug infusion, BIS of Dex group was lower than that of control group (93.9 ± 3.1 vs 51.5 ± 5.2, P < 0.05). Mean arterial pressure (MAP) and heart rate (HR) after intubation were increased in control group, but did not change in Dex group. During maintenance, there was no difference in MAP between groups, but HR of Dex group was lower compared to that of control group. End-tidal concentration (2.0 ± 0.5 vol% vs 1.4 ± 0.3 vol%, P < 0.05) and total cumulative consumption of sevoflurane (34.6 ± 3.8 ml vs 26.5 ± 5.3 ml, P < 0.05) were lower in Dex group than in control group. Recovery profiles, modified Aldrete score, postoperative nausea vomiting, and visual analogue pain score were not significantly different between groups.
Conclusions
Preanesthetic dexmetomidine 1 µg/kg single infusion is a simple, easy, and economic general anesthetic adjuvant that maintains stable hemodynamics and decrease anesthetic consumption without the change of recovery profiles.
doi:10.4097/kjae.2013.65.2.114
PMCID: PMC3766775  PMID: 24023992
Dexmedetomidine; Economics; Hemodynamics; Recovery of function; Sevoflurane
10.  General anaesthesia or conscious sedation for painful procedures in childhood cancer: the family‘s perspective 
Archives of Disease in Childhood  2003;88(3):253-257.
Background: Until recently, midazolam sedation was routinely used in our institution for bone marrow aspirates and lumbar punctures in children with cancer. It has been perceived by many doctors and nurses as being well tolerated by children and their families.
Aim: To compare the efficacy of inhalational general anaesthesia and midazolam sedation for these procedures.
Methods: A total of 96 children with neoplastic disorders, who received either inhalational general anaesthesia with sevoflurane, nitrous oxide, and oxygen (GA) or sedation with oral or nasal midazolam (SED) as part of their routine preparation for procedures were studied. The experiences of these childen were examined during their current procedure and during their first ever procedure. Main outcome measures were the degree of physical restraint used on the child, and the levels of distress and pain experienced by the child during the current procedure and during the first procedure. The family‘s preference for future procedures was also determined.
Results: During 102 procedures under GA, restraint was needed on four occasions (4%) when the anaesthetic mask was first applied, minimal pain was reported, and children were reported as distressed about 25% of the time. During 80 SED procedures, restraint was required in 94%, firm restraint was required in 66%, the child could not be restrained in 14%, median pain score was 6 (scale 0 (no pain) to 6 (maximum pain)), and 90% of the parents reported distress in their child. Ninety per cent of families wanted GA for future procedures. Many families reported dissatisfaction with the sedation regime and raised concerns about the restraint used on their child.
Conclusions: This general anaesthetic regime minimised the need for restraint and was associated with low levels of pain and distress. The sedation regime, by contrast, was much less effective. There was a significant disparity between the perceptions of health professionals and those of families with respect to how children coped with painful procedures.
doi:10.1136/adc.88.3.253
PMCID: PMC1719477  PMID: 12598395
11.  Effects of three different types of anaesthesia on perioperative bleeding control in functional endoscopic sinus surgery 
The aim of the study was to assess the effect of three different types of anaesthesia on perioperative bleeding control and to analyse the mean arterial blood pressure and heart rate in patients undergoing endoscopic paranasal sinus surgery. Ninety patients (30 women and 60 men, aged 18–85 years) scheduled to undergo functional endoscopic sinus surgery in the years 2008–2010 were identified as candidates for inclusion in the study. Patients were randomly assigned to one of three groups (30 patients each) according to the type of general anaesthesia to be administered. Groups I and II both received inhalation anaesthesia (sevoflurane for sedation) and intravenous anaesthesia (fentanyl in group I, remifentanil in group II). Anaesthesia was delivered solely via intravenous route (TIVA) in group III, with propofol used for sedation and remifentanil for analgesia. Blood pressure and heart rate were monitored during surgery and post-surgically for 4 h. Mean anaesthesia duration in groups I, II and III was 108.7 ± 20.8, 112.6 ± 22.2 and 103.7 ± 17.5 min and the surgery duration was 71.3 ± 16.7, 78.8 ± 24.2 and 66.5 ± 15.5 min, respectively. Mean blood loss during surgery was 365.0 ± 176.2, 340.0 ± 150.5 and 225.0 ± 91.7 ml, with a mean blood loss rate of 5.1 ± 2.4, 4.5 ± 2.2 and 3.4 ± 1.1 ml/min in groups I, II and III, respectively. Technologically advanced control of the drug dose with the TIVA technique allows for better control of perioperative bleeding.
doi:10.1007/s00405-012-2311-1
PMCID: PMC3669505  PMID: 23263204
Type of anaesthesia; Perioperative bleeding; Functional endoscopic sinus surgery (FESS)
12.  Practice of sedation and analgesia in German intensive care units: results of a national survey 
Critical Care  2005;9(2):R117-R123.
Introduction
Sedation and analgesia are provided by using different agents and techniques in different countries. The goal is to achieve early spontaneous breathing and to obtain an awake and cooperative pain-free patient. It was the aim of this study to conduct a survey of the agents and techniques used for analgesia and sedation in intensive care units in Germany.
Methods
A survey was sent by mail to 261 hospitals in Germany. The anesthesiologists running the intensive care unit were asked to fill in the structured questionnaire about their use of sedation and analgesia.
Results
A total of 220 (84%) questionnaires were completed and returned. The RAMSAY sedation scale was used in 8% of the hospitals. A written policy was available in 21% of hospitals. For short-term sedation in most hospitals, propofol was used in combination with sufentanil or fentanyl. For long-term sedation, midazolam/fentanyl was preferred. Clonidine was a common part of up to two-thirds of the regimens. Epidural analgesia was used in up to 68%. Neuromuscular blocking agents were no longer used.
Conclusion
In contrast to the US 'Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult', our survey showed that in Germany different agents, and frequently neuroaxial techniques, were used.
doi:10.1186/cc3035
PMCID: PMC1175921  PMID: 15774043
13.  Sedation in gastrointestinal endoscopy: Current issues 
Diagnostic and therapeutic endoscopy can successfully be performed by applying moderate (conscious) sedation. Moderate sedation, using midazolam and an opioid, is the standard method of sedation, although propofol is increasingly being used in many countries because the satisfaction of endoscopists with propofol sedation is greater compared with their satisfaction with conventional sedation. Moreover, the use of propofol is currently preferred for the endoscopic sedation of patients with advanced liver disease due to its short biologic half-life and, consequently, its low risk of inducing hepatic encephalopathy. In the future, propofol could become the preferred sedation agent, especially for routine colonoscopy. Midazolam is the benzodiazepine of choice because of its shorter duration of action and better pharmacokinetic profile compared with diazepam. Among opioids, pethidine and fentanyl are the most popular. A number of other substances have been tested in several clinical trials with promising results. Among them, newer opioids, such as remifentanil, enable a faster recovery. The controversy regarding the administration of sedation by an endoscopist or an experienced nurse, as well as the optimal staffing of endoscopy units, continues to be a matter of discussion. Safe sedation in special clinical circumstances, such as in the cases of obese, pregnant, and elderly individuals, as well as patients with chronic lung, renal or liver disease, requires modification of the dose of the drugs used for sedation. In the great majority of patients, sedation under the supervision of a properly trained endoscopist remains the standard practice worldwide. In this review, an overview of the current knowledge concerning sedation during digestive endoscopy will be provided based on the data in the current literature.
doi:10.3748/wjg.v19.i4.463
PMCID: PMC3558570  PMID: 23382625
Gastrointestinal endoscopy; Endoscopy; Sedation; Analgesia; Digestive system
14.  Clinical recovery time from conscious sedation for dental outpatients. 
Anesthesia Progress  2002;49(4):124-127.
For dental outpatients undergoing conscious sedation, recovery from sedation must be sufficient to allow safe discharge home, and many researchers have defined "recovery time" as the time until the patient was permitted to return home after the end of dental treatment. But it is frequently observed that patients remain in the clinic after receiving permission to go home. The present study investigated "clinical recovery time," which is defined as the time until discharge from the clinic after a dental procedure. We analyzed data from 61 outpatients who had received dental treatment under conscious sedation at the Hiroshima University Dental Hospital between January 1998 and December 2000 (nitrous oxide-oxygen inhalation sedation [n = 35], intravenous sedation with midazolam [n = 10], intravenous sedation with propofol [n = 16]). We found that the median clinical recovery time was 40 minutes after nitrous oxide-oxygen sedation, 80 minutes after midazolam sedation, and 52 minutes after propofol sedation. The clinical recovery time was about twice as long as the recovery time described in previous studies. In a comparison of the sedation methods, clinical recovery time differed (P = .0008), being longer in the midazolam sedation group than in the nitrous oxide-oxygen sedation group (P = .018). These results suggest the need for changes in treatment planning for dental outpatients undergoing conscious sedation.
PMCID: PMC2007416  PMID: 12779113
15.  Deep sedation for endoscopic retrograde cholangiopacreatography 
Sedation and analgesia comprise an important element of unpleasant and often prolonged endoscopic retrograde cholangiopacreatography (ERCP), contributing, however, to better patient tolerance and compliance and to the reduction of injuries during the procedure due to inappropriate co-operation. Although most of the studies used a moderate level of sedation, the literature has revealed the superiority of deep sedation and general anesthesia in performing ERCP. The anesthesiologist’s presence is mandatory in these cases. A moderate sedation level for ERCP seems to be adequate for octogenarians. The sedative agent of choice for sedation in ERCP seems to be propofol due to its fast distribution and fast elimination time without a cumulative effect after infusion, resulting in shorter recovery time. Its therapeutic spectrum, however, is much narrower and therefore careful monitoring is much more demanding in order to differentiate between moderate, deep sedation and general anesthesia. Apart from conventional monitoring, capnography and Bispectral index or Narcotrend monitoring of the level of sedation seem to be useful in titrating sedatives in ERCP.
doi:10.4253/wjge.v3.i2.34
PMCID: PMC3055942  PMID: 21403815
Deep sedation; Endoscopic retrograde cholangiopacreatography; Monitoring; Sedatives
16.  Recovery Following Sedation with Midazolam or Diazepam Alone or in Combination with Fentanyl for Outpatient Surgery 
Anesthesia Progress  1986;33(5):230-234.
Midazolam is a new water-soluble benzodiazepine with a much shorter pharmacologic half-life than diazepam. Despite this shorter pharmacologic half-life, several reports indicate that patients do not recover more rapidly after sedation with midazolam than with diazepam. The purpose of this study was to compare recovery of patients sedated with either midazolam or diazepam alone or in combination with fentanyl using the digit symbol substitution test (DSST) and Trieger test. Patients were randomly divided into treatment groups and recovery tests were administered to the patients prior to sedation and at 60, 120, and 180 minutes after achieving a standardized sedative endpoint. Patients who received midazolam alone had significantly fewer numbers of correct reponses on the DSST than patients who received midazolam plus fentanyl or diazepam with or without fentanyl. When midazolam was combined with fentanyl there was no significant difference between results obtained on the DSST when compared with either diazepam group. Comparisons between all groups using dots missed or millimeter deviation on the Trieger test showed no statistical difference between any groups. These data indicate that midazolam as a single IV agent has a slightly prolonged recovery phase compared to diazepam. The addition of fentanyl to the sedation regimen allows reduction in the midazolam dose resulting in a recovery time comparable to that of diazepam.
PMCID: PMC2177484  PMID: 3465258
17.  Analysis of Oxygen Saturations Recorded During Dental Intravenous Sedations: A Retrospective Quality Assurance of 3500 Cases 
Anesthesia Progress  2011;58(3):113-120.
The death of a patient under sedation in New South Wales, Australia, in 2002 has again raised the question of the safety of dental sedation. This study sought answers to 2 questions: Can safe oxygen saturation levels (≥94%) be consistently maintained by a single operator/sedationist? Does the additional use of propofol, in subanesthetic doses, increase the risk of exposure to hypoxemia? Three thousand five hundred cases generated between 1996 and 2006 were randomly examined and divided into 2 subcohorts: 1750 patients were sedated with midazolam and fentanyl, and 1750 patients received propofol, in subanesthetic increments, in addition to midazolam and fentanyl. Initial sedation was established using midazolam and fentanyl in both subcohorts. The second subcohort received propofol during times of noxious stimulation. Patient exposure to 2 or more oxygen desaturations below 94% was uncommon. The variables that were significantly associated with low saturations were age, gender, and weight. Neither the dose of midazolam nor the additional use of propofol was a significant risk factor. ASA classification (I or II) was not a determinant of risk. The data, within the limitations of the study, showed that a single operator/sedationist, supported by a well-trained team of nurses, can consistently maintain safe oxygen saturation levels. The additional use of propofol did not increase exposure to hypoxemia.
doi:10.2344/09-00001.1
PMCID: PMC3167154  PMID: 21882986
Dental sedation; Safe oxygen saturation levels; Propofol
18.  Effects of repeat exposure to inhalation anesthetics on liver and renal function 
Background:
Cross hypersensitivity to inhalation anesthetics has not been studied. The aim of this study was to investigate it by comparing liver and renal function after repeated anesthesia with sevoflurane and isoflurane retrospectively.
Materials and Methods:
The adult patients who received general anesthesia twice within the interval of 14 days to 1 year were retrospectively analyzed. Those who received sevoflurane anesthesia twice (SS group, 53 cases), isoflurane anesthesia twice (II group, 31 cases), sevoflurane followed by isoflurane anesthesia (SI group, 29 cases), isoflurane followed by sevoflurane anesthesia (IS group, 35 cases), and propofol–fentanyl anesthesia twice (PP group, 58 cases) were enrolled. Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (Bil), gamma-glutamyl transpeptidase (γ-GTP), blood urea nitrogen (BUN), and creatinine (Cr) measured 1-3, 5-8, and 12-16 days after surgery were investigated.
Results:
In the IS group, the number of the patients with abnormal values of ALT and γ-GTP 5–8 days after surgery were significantly smaller at second anesthesia compared to the first anesthesia. The number of the patients with abnormal values of AST, ALT, and γ-GTP were significantly larger in the II group than the SS and PP groups. The number of patients who had higher values in each parameter at second anesthesia compared to the first anesthesia was not different among the groups.
Conclusions:
Sevoflurane and isoflurane might have no cross hypersensitivity. Both anesthetics might not have any additional risks to increase liver and renal damage by second anesthesia.
doi:10.4103/0970-9185.105809
PMCID: PMC3590549  PMID: 23493664
General anesthesia; isoflurane; kidney; liver; propofol; sevoflurane
19.  Anterograde Amnesia as a Possible Postoperative Complication of Midazolam as an Agent for Intravenous Conscious Sedation 
Anesthesia Progress  1988;35(4):160-162.
Anterograde amnesia is often considered to be a beneficial effect of intravenous conscious sedation. The recently introduced benzodiazepine, midazolam, has associated with its administration a significant anterograde amnesic period. In the case presented here, a healthy young female presented for third molar extraction under midazolam conscious sedation and local anesthesia. After uncomplicated removal of the teeth and clinically adequate recovery from sedation, it was noted that the patient had swallowed the postsurgical gauze packs. Efforts at recovery of the gauze packs were futile. Follow-up discussion with the patient revealed a complete lack of recall of all events occurring for up to an hour or more after the administration of intravenous midazolam. The need for written and oral postoperative instructions to both the patient and his/her escort is emphasized.
PMCID: PMC2167955  PMID: 3166354
20.  Age-related requisite concentration of sevoflurane for adequate sedation with combined epidural-general anesthesia 
Korean Journal of Anesthesiology  2013;64(6):489-493.
Background
The requisite anesthetic concentration of sevoflurane required to obtain adequate sedation when sufficient analgesics are supplied has not been determined. The purpose of this study was to determine the requisite age-associated concentration of sevoflurane to obtain an adequate level of anesthesia during combined epidural-general anesthesia by bispectral index (BIS) monitoring.
Methods
Twenty-seven elective abdominal surgery patients (American Society of Anesthesiologists physical status I-II) were enrolled. The patients were divided into two groups of more or less than 60 years of age. We investigated the concentration of sevoflurane required to obtain an adequate sedation level during combined epidural-general anesthesia, maintaining the BIS value between 40 and 60.
Results
The requisite sevoflurane concentration required to keep the BIS value at 40-60 was not stable during surgery. In the younger group, the maximum concentration of sevoflurane needed during surgery was 1.95 ± 0.14 (95% confidence interval: 1.87-2.10) vol%, while it was 1.54 ± 0.44 (95% confidence interval: 1.27-1.80) vol% in the older group (P < 0.01).
Conclusions
The requisite concentration of sevoflurane required with combined epidural-general anesthesia was 2.5 vol% for the younger group and 2.0 vol% for the older group as determined by BIS monitoring. We believe that these percentages are sufficient to avoid awareness during surgery with adequate analgesia.
doi:10.4097/kjae.2013.64.6.489
PMCID: PMC3695244  PMID: 23814647
Bispectral index monitoring; Epidural anesthesia; Inhalation anesthetics; Sevoflurane
21.  Efficiency and safety of inhalative sedation with sevoflurane in comparison to an intravenous sedation concept with propofol in intensive care patients: study protocol for a randomized controlled trial 
Trials  2012;13:135.
Background
State of the art sedation concepts on intensive care units (ICU) favor propofol for a time period of up to 72 h and midazolam for long-term sedation. However, intravenous sedation is associated with complications such as development of tolerance, insufficient sedation quality, gastrointestinal paralysis, and withdrawal symptoms including cognitive deficits. Therefore, we aimed to investigate whether sevoflurane as a volatile anesthetic technically implemented by the anesthetic-conserving device (ACD) may provide advantages regarding ‘weaning time’, efficiency, and patient’s safety when compared to standard intravenous sedation employing propofol.
Method/Design
This currently ongoing trial is designed as a two-armed, monocentric, randomized prospective phase II study including intubated intensive care patients with an expected necessity for sedation exceeding 48 h. Patients are randomly assigned to either receive intravenous sedation with propofol or sevoflurane employing the ACD. Primary endpoint is the comparison of the ‘weaning time’ defined as the time required from discontinuation of the sedating agent until sufficient spontaneous breathing occurs. Moreover, sedation depth evaluated by Richmond Agitation Sedation Scale and parameters of patient’s safety (that is, vital signs, laboratory monitoring of organ function) as well as the duration of mechanical ventilation and overall stay on the ICU are analyzed and compared. An intention-to-treat analysis will be carried out with all patients for whom it will be possible to define a wake-up time. In addition, a per-protocol analysis is envisaged. Completion of patient recruitment is expected by the end of 2012.
Discussion
This clinical study is designed to evaluate the impact of sevoflurane during long-term sedation of critically ill patients on ‘weaning time’, efficiency, and patient’s safety compared to the standard intravenous sedation concept employing propofol.
Trial registration
EudraCT2007-006087-30; ISCRTN90609144
doi:10.1186/1745-6215-13-135
PMCID: PMC3502585  PMID: 22883020
Inhalative sedation; Intravenous sedation; Intensive care; Sevoflurane
22.  Effect of intravenous infusion of dexmedetomidine on perioperative haemodynamic changes and postoperative recovery: A study with entropy analysis 
Indian Journal of Anaesthesia  2012;56(6):542-546.
Background:
Dexmedetomidine, an α2 agonist, when used as an adjuvant in general anaesthesia attenuates stress response to various noxious stimuli, maintains perioperative haemodynamic stability and provides sedation without significant respiratory depression postoperatively.
Methods:
Sixty patients were randomly divided into two groups of 30 each. In group A, fentanyl 2 μg/kg and in group B dexmedetomidine were given intravenously as loading dose of 1 μg/kg over 10 min prior to induction. After induction with thiopentone, in group B, dexmedetomidine was given as infusion at a dose of 0.2–0.8 μg/kg. Sevoflurane was used as inhalation agent in both groups. Haemodynamic variables and entropy (response entropy and state entropy) were recorded continuously. Postoperative sedation and recovery were assessed by sedation score and modified Aldrete's score, respectively.
Results:
Dexmedetomidine significantly attenuates stress response at intubation with lesser increase in heart rate (10% vs. 17%), systolic blood pressure (6% vs. 23%) and diastolic blood pressure (7% vs. 20%) as compared to the control group (P<0.05). Intraoperatively, an average of 8% fall in systolic blood pressure and 8.16% fall in diastolic pressure in the test group as compared to 3.6% rise in systolic and 3.3% in diastolic pressure of the control group was observed. Postoperatively, the test group showed significant sedation at 2 h as compared to the control group (P=0.00) and recovery was better in the control group for the first 2 h post extubation.
Conclusion:
Dexmedetomidine attenuates various stress responses during surgery and maintains the haemodynamic stability when used as an adjuvant in general anaesthesia. Also, the sedative action of dexmedetomidine delays recovery for the first few hours post extubation.
doi:10.4103/0019-5049.104571
PMCID: PMC3546240  PMID: 23325938
Dexmedetomidine; entropy; perioperative haemodynamics; recovery
23.  Average recovery time from a standardized intravenous sedation protocol and standardized discharge criteria in the general dental practice setting. 
Anesthesia Progress  2002;49(3):77-81.
Intravenous sedation has been used in dentistry for many years because of its perceived advantages over general anesthesia, including shorter recovery times. However, there is limited literature available on recovery from intravenous dental sedation, particularly in the private general practice setting. The aim of this study was to describe the recovery times when sedation was conducted in private dental practice and to consider this in relation to age, weight, procedure type, and procedure time. The data were extracted from the intravenous sedation records available with 1 general anesthesia-trained dental practitioner who provides ambulatory sedation services to a number of private general dental practices in the Perth, Western Australia Metropolitan Area. Standardized intravenous sedation techniques as well as clear standardized discharge criteria were utilized. The sedatives used were fentanyl, midazolam, and propofol. Results from 85 patients produced an average recovery time of 19 minutes. Recovery time was not associated with the type or length of dental procedures performed.
PMCID: PMC2007342  PMID: 15384295
24.  Sedative Efficacy of Propofol in Patients Intubated/Ventilated after Coronary Artery Bypass Graft Surgery 
Background:
Sedation after open heart surgery is important in preventing stress on the heart. The unique sedative features of propofol prompted us to evaluate its potential clinical role in the sedation of post-CABG patients.
Objectives:
To compare propofol-based sedation to midazolam-based sedation after coronary artery bypass graft (CABG) surgery in the intensive care unit (ICU).
Patients and Methods:
Fifty patients who were admitted to the ICU after CABG surgery was randomized into two groups to receive sedation with either midazolam or propofol infusions; and additional analgesia was administered if required. Inclusion criteria were as follows: patients 40-60 years old, hemodynamic stability, ejection fraction (EF) more than 40%; exclusion criteria included patients who required intra-aortic balloon pump or inotropic drugs post-bypass. The same protocol of anesthetic medications was used in both groups. Depth of sedation was monitored using the Ramsay sedation score (RSS). Invasive mean arterial pressure (MAP) and heart rate (HR), arterial blood gas (ABG) and ventilatory parameters were monitored continuously after the start of study drug and until the patients were extubated.
Results:
The depth of sedation was almost the same in the two groups (RSS=4.5 in midazolam group vs 4.7 in propofol group; P = 0.259) but the total dose of fentanyl in the midazolam group was significantly more than the propofol group (12.5 mg/hr vs 4 mg/hr) (P = 0.0039). No significant differences were found in MAP (P = 0.51) and HR (P = 0.41) between the groups. The mean extubation time in patients sedated with propofol was shorter than those sedated with midazolam (102 ± 27 min vs 245 ± 42 min, respectively; P < 0.05) but the ICU discharge time was not shorter (47.5 hr vs 36.3 hr, respectively; P = 0.24).
Conclusions:
Propofol provided a safe and acceptable sedation for post-CABG surgical patients, significantly reduced the requirement for analgesics, and allowed for more rapid tracheal extubation than midazolam but did not result in earlier ICU discharge.
doi:10.5812/aapm.17109
PMCID: PMC3961039  PMID: 24660162
Propofol; Analgesics; Coronary Artery Bypass; Deep Sedation; Midazolam; Airway Extubation; Length of Stay
25.  Response surface model predictions of emergence and response to pain in the recovery room: an evaluation of patients emerging from an isoflurane and fentanyl anesthetic 
Anesthesia and analgesia  2010;111(2):380-386.
Introduction
Sevoflurane - remifentanil interaction models that predict responsiveness and response to painful stimuli have been evaluated in patients undergoing elective surgery. Preliminary evaluations of model predictions were found to be consistent with observations in patients anesthetized with sevoflurane, remifentanil and fentanyl. The present study explored the feasibility of adapting the predictions of sevoflurane-remifentanil interaction models to an isoflurane-fentanyl anesthetic. We hypothesized that model predictions adapted for isoflurane and fentanyl are consistent with observed patient responses and are similar to the predictions observed in our prior work with sevoflurane-remifentanil/fentanyl anesthetics.
Methods
Twenty-five patients scheduled for elective surgery received a fentanyl-isoflurane anesthetic. Model predictions of unresponsiveness were recorded at emergence and predictions of a response to noxious stimulus were recorded when patients first required analgesics in the recovery room. Model predictions were compared to observations with graphical and temporal analyses. Results were also compared to our prior predictions following a sevoflurane-remifentanil/fentanyl anesthetic.
Results
While patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (≥ 99%). Following termination of the anesthetic, model predictions of responsiveness well described the actual fraction of patients observed to be responsive during emergence. Half of the patients awoke within 2 minutes of the 50% model predicted probability of unresponsiveness; 70% awoke within 4 minutes. Similarly, predictions of a response to a noxious stimulus were consistent with the number of patients who required fentanyl in the recovery room. Model predictions following an isoflurane-fentanyl anesthetic were similar to model predictions following a sevoflurane-remifentanil/fentanyl anesthetic.
Discussion
Results confirmed our study hypothesis; model predictions for unresponsiveness and no response to painful stimuli, adapted to isoflurane-fentanyl, were consistent with observations. These results were similar to our prior study comparing model predictions and patient observations following a sevoflurane-remifentanil/fentanyl anesthetic.
doi:10.1213/ane.0b013e3181b11289
PMCID: PMC2891181  PMID: 19820239

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