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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.  A Comparison of Fospropofol to Midazolam for Moderate Sedation During Outpatient Dental Procedures 
Anesthesia Progress  2013;60(4):162-177.
Moderate intravenous (IV) sedation combined with local anesthesia is common for outpatient oral surgery procedures. An ideal sedative agent must be safe and well tolerated by patients and practitioners. This study evaluated fospropofol, a relatively new sedative/hypnotic, in comparison to midazolam, a commonly used benzodiazepine, for IV moderate sedation during oral and maxillofacial surgery. Sixty patients were randomly assigned to either the fospropofol or the midazolam group. Each participant received 1 μg/kg of fentanyl prior to administration of the selected sedative. Those in the fospropofol group received an initial dose of 6.5 mg/kg, with 1.6 mg/kg supplemental doses as needed. Those in the midazolam group received initial doses of 0.05 mg/kg, followed by 0.02 mg/kg supplemental doses. The quality of sedation in each patient was evaluated with regard to (a) onset of sedation, maintenance, and recovery profile; (b) patient and surgeon satisfaction; and (c) hemodynamic stability and adverse effects. The fospropofol group demonstrated shorter physical recovery times than midazolam patients, taking a mean of 11.6 minutes versus 18.4 minutes for physical recovery (P = .007). Cognitive recovery comparison did not find any difference with a mean of 7.5 minutes versus 8.8 minutes between the 2 drug groups (P = .123). The fospropofol group had a higher rate of local anesthetic injection recall (90.5 vs 44.4%, P = .004). Other parameters of recall were comparable. Two adverse effects demonstrated significance, with more patients in the midazolam group experiencing tachycardia (48.2 vs 9.4%, P = .001), and more patients in the fospropofol group experiencing perineal discomfort (40.6 vs 0, P < .001). No significant difference was found in any other measures of sedation safety, maintenance, or satisfaction. Fospropofol, when administered intravenously by a dentist anesthesiologist at the indicated dose in this study, appears to be a safe, well-tolerated alternative to midazolam for intravenous moderate sedation during minor oral surgery procedures.
PMCID: PMC3891457  PMID: 24423419
Fospropofol; Midazolam; Moderate sedation; Outpatient surgery; IV conscious sedation; Benzodiazepine; Propofol
3.  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.
PMCID: PMC3468288  PMID: 23050750
Propofol; Ketamine; Remifentanil; Deep sedation; TIVA
4.  Recovery profile of patients undergoing nasal surgical procedures: a comparison between sevoflurane and propofol 
To compare the recovery profile of sevoflurane and propofol in nasal surgical procedures.
A prospective, double blind, randomized study
King Abdul Aziz University Hospital, Riyadh, Saudi Arabia, a tertiary care teaching hospital, attached with King Saud University, Riyadh Saudi Arabia.
60 ASA I–II patients age between 18–35 years, and weighing 50-80 kg, scheduled for nasal surgical procedures.
Patients were assigned randomly to one of the two groups, the Sevoflurane Group-S (n = 30) & the Propofol Group-P (n = 30). Anesthetic induction was carried out using propofol 2.0mg/ both the groups. Cis-atracurium 0.15mg/kg was given for intubation. Airway was protected with a throat pack around the endo-tracheal tube. Fentanyl 1microgram/kg was given as bolus followed by infusion at a rate of 1 microgram/kg/ hour. Anesthesia was maintained with sevoflurane 2% in Group-S, and propofol infusion at a rate of 200 microgram/kg/min. in Group-P. 50% oxygen in nitrous oxide was given in both the groups. At the end of surgery, patients were extubated after reversal of the neuromuscular block. Immediate recovery was assessed by recording the time to breathe spontaneously, time to extubation, and time of spontaneous eyes movements from the time of giving reversal. Ketoprofen 1.5mg/kg intramuscularly was given to all patients before transfer to (PACU). In PACU, sedation score was assessed for 45 min. Intermediate recovery was assessed by TDT and DSST at 15, 30 and 45 min. Time taken to state name and father’s name was recorded.
Patients in Group-S breathed significantly earlier than those in Group-P. Group-P showed significantly better performance with TDT at 45 min and with DSST at 30 and 45 min.
We conclude that both sevoflurane and propofol provide early and comparable post anesthesia recovery for patients undergoing nasal surgical procedures.
PMCID: PMC3450520  PMID: 23120519
Propofol; Sevoflurane; Recovery profile; Emergence; Anesthesia; Nasal Surgery
5.  Sedative Efficacy of Propofol in Patients Intubated/Ventilated after Coronary Artery Bypass Graft Surgery 
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.
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.
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).
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.
PMCID: PMC3961039  PMID: 24660162
Propofol; Analgesics; Coronary Artery Bypass; Deep Sedation; Midazolam; Airway Extubation; Length of Stay
6.  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.
PMCID: PMC3683682  PMID: 23801836
Endoscopy; Deep sedation; Anesthetic administration; Anesthetic dose; Adverse effects
7.  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.
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.
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.
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.
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)
PMCID: PMC3607964  PMID: 23170921
Balanced propofol sedation; Alfentanil; Fentanyl; Deep sedation; Diagnostic endoscopy; Cost benefit
8.  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.
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.
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.
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
PMCID: PMC3502585  PMID: 22883020
Inhalative sedation; Intravenous sedation; Intensive care; Sevoflurane
9.  Sevoflurane-emergence agitation: Effect of supplementary low-dose oral ketamine premedication in preschool children undergoing dental surgery 
Saudi Journal of Anaesthesia  2009;3(2):61-66.
Background and Objectives:
The use of sevoflurane in pediatric anesthesia, which could enable a more rapid emergence and recovery, is complicated by the frequent occurrence of post-anesthesia agitation. This study aims to test the efficacy of adding a low dose of ketamine orally, as a supplement to the midazolam-based oral premedication for reducing sevoflurane-related emergence agitation.
Materials and Methods:
Ninety-two preschool children, aged between two and six years, with an American Society of Anesthesiologists physical status I or II, scheduled for elective dental filling and extractions under general anesthesia were included. The patients were allocated into two groups: Group M (46 patients) received oral midazolam 0.5 mg/kg, mixed with ibuprofen 10 mg/kg, while group KM (46 patients) received a similar premedication mixture, in addition to ketamine 2 mg/kg. The acceptance of the drug mixture, the onset of action, and the occurrence of vomiting were monitored over the next 30 minutes. Induction of anesthesia was carried out using sevoflurane 8 Vol% in 100% oxygen via face mask. Anesthesia was maintained with sevoflurane 1.5-2 Vol% in an oxygen-nitrous oxide mixture. After extubation, the standard scoring scale was used for assessing the quality of emergence. Agitation parameters were measured using a five-point scale. Agitated children were managed by giving intravenous increments of fentanyl 1 μg/ kg. The time of hospital discharge allowance was recorded.
Drug palatability, vomiting, and onset of action of premedication; showed no significant differences between both groups. Time of eye opening after discontinuation of sevoflurane showed no significant differences between both groups. Postoperative agitation score and rescue fentanyl consumption were higher in group M than in group KM on admission to the PACU (P < 0.01). The time of hospital discharge allowance in group M was longer than in group KM (P < 0.05).
Adding a low dose of oral ketamine to midazolam-based oral premedication in preschool children undergoing dental surgery reduced sevoflurane-related emergence agitation without delaying discharge.
PMCID: PMC2876942  PMID: 20532105
Agitation; ketamine; midazolam; pediatric anesthesia; premedication; sevoflurane
10.  Effects of isoflurane, sevoflurane, and desflurane on platelet function: A prospective, randomized, single-blind, in vivo study 
The primary physiologic function of platelets is to facilitate hemostasisby aggregation. Volatile anesthetics have been reported to decrease platelet aggregation in vivo and in vitro.
The aim of this study was to investigate the hematologic effectsof the anesthetics isoflurane, sevoflurane, and desflurane on hemoglobin (Hb), hematocrit (Hct), platelet count, activated partial thromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR), and platelet aggregation after minor surgery.
Patients aged 20 to 60 years who were scheduled to undergominor surgery and American Society of Anesthesiologists physical status P1 or P2 (healthy or mild systemic disease) were randomized to 1 of 3 groups: 1 minimum alveolar concentration (MAC) of isoflurane, sevoflurane, or desflurane. None of the patients received premedication. Anesthesia was induced using IV thiopental 5 to 6 mg/kg, fentanyl 1 to 2 μg/kg, and vecuronium 0.1 mg/kg, and maintained with 1 MAC of isoflurane, sevoflurane, or desflurane in 66% nitrous oxide and 33% oxygen. Vecuronium 0.03 mg/kg was given when necessary for muscle relaxation. All patients were monitored throughout surgery; isotonic saline was given at a rate of 5 mL/kg · h. Hematologic studies were performed preoperatively, 15 minutes after intubation, and 1 hour after the end of surgery. Platelet aggregation tests were performed in a laboratory using a platelet function analyzer (PFA), collagen/epinephrine PFA test cartridges, collagen/adenosine diphosphate PFA test cartridges, and PFA trigger solution.
This prospective, randomized, single-blind, in vivo study was conducted at Gevher Nesibe Teaching Hospital, Erciyes University, Kayseri, Turkey. Thirty patients (15 men, 15 women) were randomized to the 3 treatment groups (each, n = 10). Hb, Hct, platelet count, aPTT, PT, and INR were statistically similar between all 3 groups. The measured parameters were not significantly different between the isoflurane and desflurane groups at any time point. However, in the sevoflurane group, mean (5D) platelet aggregation was significantly delayed 15 minutes after intubation and 1 hour after surgery compared with the preoperative values (collagen/epinephrine, 81.70 [9.85] seconds vs 196.20 [27.84] seconds and 115.40 [25.80] seconds; both, P < 0.05).
In this study of the effects of isoflurane, sevoflurane, and desflurane in patients undergoing minor surgery, clinically relevant antithrombotic effects were observed 15 minutes after intubation with all 3 drugs, although the effects in patients receiving sevoflurane were significantly greater compared with those in patients receiving isoflurane and desflurane. The antithrombotic effects of isoflurane and desflurane were not continued at 1 hour after surgery; however, the inhibitory effects of sevoflurane on platelet function were continued at 1 hour after surgery but were significantly decreased from levels found at 15 minutes after intubation.
PMCID: PMC3964580  PMID: 24672136
isoflurane; sevoflurane; desflurane; platelet function; coagulation
11.  Improving successful rate of transcranial electrical motor-evoked potentials monitoring during spinal surgery in young children 
European Spine Journal  2011;21(5):980-984.
This prospective study was to investigate the successful rate of intraoperative motor evoked potentials (MEP) monitoring for children (<12 years old) with congenital scoliosis.
Materials and methods
A consecutive series of 27 young children (7 girls and 20 boys; from 1 to 11 years old) between September 2007 and November 2009, were enrolled to this study. 12 patients received general anesthesia based on TIVA, induced with propofol 2–4 mg/kg and fentanyl 3–5 µg/kg followed by a continuous infusion of propofol (20–150 µg/kg/min, at mean of 71.7 µg/kg/min). The other 15 patients received combined inhalation and intravenous anesthesia, induced with sevoflurane and fentanyl 3–5 µg/kg and maintained by sevoflurane (0.5–1%). The maintenance of anaesthesia management was performed with stable physiological parameters during surgery.
Intraoperative MEP monitoring was successfully performed in all patients, while SEP was successfully performed in 26 of 27 patients. There was no significant difference of successful rates between SEP and MEP monitoring (P > 0.05). As well, no difference in MEP successful rates was observed in two groups with different anesthetic techniques. No wake-up test and no post-operative neurological deficits occurred in this series of patients.
Low dose anesthesia by either TIVA with propofol or sevoflurane-based mixture anesthesia protocol can help the intraoperative spinal cord monitoring to successfully elicit MEP and perform reliable monitoring for patients below 12 years of age.
PMCID: PMC3337921  PMID: 21874623
Intraoperative spinal cord monitoring; Motor evoked potentials (MEP); Somatosensory evoked potentials (SEP); Total intravenous anesthesia (TIVA); Congenital scoliosis
12.  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.
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.
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.
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.
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.
PMCID: PMC3766775  PMID: 24023992
Dexmedetomidine; Economics; Hemodynamics; Recovery of function; Sevoflurane
13.  A Comparison between Sedative Effect of Propofol-Fentanyl and Propofol-Midazolam Combinations in Microlaryngeal Surgeries 
Considering the growing trend of laryngeal surgeries and the need to protect the airway during and after surgery, among several therapeutic regimens to induce sedation, two regimens of propofol-fentanyl and propofol-midazolam were compared in microlaryngeal surgeries.
Forty ASA I-II class patients undergoing microlaryngeal surgeries and referring routinely for postoperative visits were randomly recruited into two groups. For all the patients, 0.5 mg/Kg of propofol was used as bolus and then, 50 mcg/Kg/min of the drug was infused intravenously. For one group, 0.03 mg/Kg bolus of midazolam and for the other group, 2 mcg/Kg bolus of fentanyl was administered in combination with propofol. Ramsay system was used in order to evaluate the effect of the two drugs in inducing sedation. The need for additional dose, blood pressure, heart rate, arterial blood oxygen saturation, and also recovery time and adverse effects such as nausea/vomiting and recalling intra-operative memories, were assessed.
The patients in the two groups were not statistically different regarding the number of patients, age, sex, preoperative vital signs, the need for additional doses of propofol, systolic blood pressure and mean systolic blood pressure during laryngoscopy. However, mean systolic blood pressure 1 min after removal of laryngoscope returned faster to the baseline in midazolam group (p < 0.01). Mean heart rate returned sooner to the baseline in fentanyl group following removal of stimulation. Besides, heart rate showed a more reduction following administration of fentanyl (p < 0.02). Mean arterial blood oxygen saturation during laryngoscopy significantly decreased in fentanyl group (p < 0.05) compared to the other group. The time it took to achieve a full consciousness was shorter in midazolam group (p < 0.01). Nausea/vomiting was significantly more prevalent in fentanyl group while the patients in midazolam group apparently experienced more of amnesia, comparatively (p < 0.01).
Inducing laryngeal block and local anesthesia using propofol-midazolam regimen is not only associated with a more rapid recovery and less recalling of unpleasant memories, but also better in preventing reduction of arterial oxygen saturation during laryngoscopy compared with propofol-fentanyl regimen.
PMCID: PMC3813093  PMID: 24250451
Sedation; Microlaryngeal surgery; Propofol; Midazolam; Fentanyl
14.  Effects of repeat exposure to inhalation anesthetics on liver and renal function 
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.
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.
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.
PMCID: PMC3590549  PMID: 23493664
General anesthesia; isoflurane; kidney; liver; propofol; sevoflurane
15.  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.
PMCID: PMC2929513  PMID: 20811603
16.  Effects of sevoflurane and propofol on right ventricular function and pulmonary circulation in patients undergone esophagectomy 
Object: Sevoflurane and propofol are both widely used in clinical anesthesia. The aim of this study is to compare the effects of sevoflurane and propofol on right ventricular function and pulmonary circulation in patients receiving esophagectomy. Methods: Forty adult patients undergoing an elective open-chest thoracotomy for esophagectomy were randomized to receive either propofol (n=20) or sevoflurane (n=20) as the main anesthetic agent. The study was performed in Changzheng Hospital. Hemodynamic data were recorded at specific intervals: before the surgery (T0), BIS values reaching 40 after anesthesia induction (T1), two-lung ventilation (T2), ten minutes after one-lung ventilation (T3), the end of the operation (T4) using PiCCO2 and Swan-Ganz catheter. Results: CI, RVEF, RVSWI and RVEDVI were significantly smaller in propofol group than those in sevoflurane group throughout the surgery (P<0.05). However, SVRI was significantly greater in propofol group than that in sevoflurane group (P<0.05). Compared with the patients in propofol group, the patients who received sevoflurane had a greater reduction in OI and increase in Os/Ot (P<0.05). And, PVRI was significantly smaller in sevoflurane group than in propofol group (P<0.05). Conclusion: Anesthesia with sevoflurane preserved better right ventricular function than propofol in patients receiving esophagectomy. However, propofol improved oxygenation and shunt fraction during one-lung ventilation compared with sevoflurane anesthesia. To have the best effect, anesthesiologists can choose the two anesthetics flexibly according to the monitoring results.
PMCID: PMC3885482  PMID: 24427348
Sevoflurane; propofol; right ventricular function; pulmonary circulation; esophagectomy
17.  Additional clinical observations utilizing bispectral analysis. 
Anesthesia Progress  2000;47(3):84-86.
Additional observations were made in the use of the bispectral (BIS) index with the use of ketamine and in performing general anesthesia without the use of local anesthesia in nonintubated patients. Twenty-five subjects undergoing extraction procedures in an outpatient setting were analyzed using bispectral analysis with ketamine and midazolam. Despite repeated injections of midazolam during the procedure, only transient decreases of the BIS occurred to the 80s, with a low value of 77 in all but 1 patient where ketamine was used. In comparison, values in the 50-70 range are typically seen immediately after the administration of sedative doses of midazolam, propofol, or methohexital. In the second study, once propofol anesthesia was initiated, BIS readings in the 30s were commonly seen in patients during their procedure. The lowest BIS level observed was 18. Bispectral analysis was useful to trend the present anesthetic state and adjust the dose of propofol accordingly. In no case was laryngospasm or total airway obstruction observed. In 1 case, partial airway obstruction secondary to retro-positioning of the tongue occurred with a subsequent decrease in oxygen saturation to 89%. This was rectified by repositioning the patient to alleviate the obstruction. Consistent with previous studies utilizing ketamine, BIS values are consistently higher when compared with other hypnotic agents. With the subsequent injection of midazolam, the BIS level did not decrease to anticipated levels. In the final study reviewed, when local anesthesia was not used during general anesthesia, bispectral analysis was a useful adjunct in helping maintain a steady state of general anesthesia in nonintubated patients undergoing third molar extractions. Bispectral analysis offers additional information on the depth of the hypnotic state and is useful in helping control the depth of anesthesia. A limitation of the index includes the inability to titrate the level of sedation induced by hypnotic agents such as midazolam when ketamine is concomitantly administered.
PMCID: PMC2149025  PMID: 11432161
18.  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.
This randomized study was conducted to compare the hemodynamic changes and emergence characteristics of sevoflurane versus propofol anesthesia for microlaryngeal surgery.
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.
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.
We found that sevoflurane showed advantage over propofol in respect of intraoperative cardiovascular stability without increasing recovery time.
PMCID: PMC3591559  PMID: 23493938
General anesthesia; hemodynamic changes; microlaryngeal surgery; propofol; recovery; sevoflurane
19.  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.
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.
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.
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.
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.
PMCID: PMC2891181  PMID: 19820239
20.  Induced hypotension for functional endoscopic sinus surgery: A comparative study of dexmedetomidine versus esmolol 
Saudi Journal of Anaesthesia  2013;7(2):175-180.
A comparative study to evaluate the efficacy of dexmedetomidine as a hypotensive agent in comparison to esmolol in Functional Endoscopic Sinus Surgery (FESS).
Forty patients ASA I or II scheduled for FESS were equally randomly assigned to receive either dexmedetomidine 1 μg/Kg over 10 min before induction of anesthesia followed by 0.4-0.8 μg/Kg/h infusion during maintenance (DEX group), or esmolol, loading dose 1mg/kg was infused over one min followed by 0.4-0.8 mg/kg/h infusion during maintenance (E group) to maintain mean arterial blood pressure (MAP) between (55-65 mmHg). General anesthesia was maintained with sevoflurane 2%-4%. The surgical field was assessed using Average Category Scale and average blood loss was calculated. Hemodynamic variables (MAP and HR); arterial blood gas analysis; plasma cortisol level; intraoperative fentanyl consumption; Emergence time and total recovery from anesthesia (Aldrete score ≥9) were recorded. Sedation score was determined at 15, 30, 60 min after tracheal extubation and time to first analgesic request was recorded.
Both DEX group and E group reached the desired MAP (55-65 mmHg) with no intergroup differences in MAP or HR. The for the quality of the surgical filed in the range of MAP (55-65 mmHg) were <=2 with no significant differences between group scores during hypotensive period. Mean intraoperative fentanyl consumption was significantly lower in DEX group than E group. Cortisol level showed no significant changes between or within groups. No significant changes were observed in arterial blood gases. Emergence time and time to achieve Aldrete score ≥9 were significantly lower in E group compared with DEX group. The sedation score were significantly lower in E group compared with DEX group at 15 and 30 minutes postoperatively. Time to first analgesic request was significantly longer in DEX group.
Both dexmedetomidine or esmolol with sevoflurane are safe agents for controlled hypotension and are effective in providing ideal surgical field during FESS. Compared with esmolol, dexmedetomidine offers the advantage of inherent analgesic, sedative and anesthetic sparing effect.
PMCID: PMC3737695  PMID: 23956719
Controlled hypotension; dexmedetomidine; esmolol; functional endoscopic sinus surgery
21.  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
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.
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.
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.
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.
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.
PMCID: PMC3546240  PMID: 23325938
Dexmedetomidine; entropy; perioperative haemodynamics; recovery
23.  Two-agent analgesia versus acetaminophen in children having bilateral myringotomies and tubes surgery 
Paediatric anaesthesia  2010;20(11):1028-1035.
The objective of this study was to determine whether the incidence of emergence agitation (EA) can be reduced by adding an additional, faster onset, non-IV analgesic, intranasal fentanyl or intramuscular (im) ketorolac to rectal acetaminophen.
To compare the incidence of EA after analgesia with two agents vs acetaminophen alone in pediatric patients after bilateral myringotomy procedures (BM&T).
Anesthesia for BM&T is usually performed with volatile anesthetics as a single agent without securing intravenous access. The anesthetic agent most commonly used is sevoflurane; however, EA has been reported in up to 67% of patients. Emergence agitation is distressing for parents, can impair the ability of nursing staff to adequately monitor the child, and can result in a child injuring him/herself if it is severe.
A standardized anesthetic was used with oral midazolam premedication and sevoflurane for induction, and maintenance of anesthesia. All patients received 40 mg·kg−1 rectal acetaminophen, group 1 received acetaminophen alone, group 2 received acetaminophen and 1 mcg·kg−1 of intranasal fentanyl, and group 3 received acetaminophen and 1 mg·kg−1 of intramuscular ketorolac. Incidence of EA was compared using chi-square test between the acetaminophen group alone vs the two-agent analgesia groups combined.
There were no differences in demographic and clinical characteristics between the two groups. There were no statistically significant differences between the three groups for the incidence of EA at any time point during recovery from anesthesia nor were there any significant differences in pain scores or side effects. No significant side effects because of the administration of a second analgesic agent were reported.
We conclude that two-agent analgesia is not superior to acetaminophen alone for decreasing the incidence of EA after inhalation anesthesia with sevoflurane for BM&T surgery. Our overall incidence of EA was low compared to previous studies, which could potentially have decreased our ability to detect differences between groups.
PMCID: PMC4005868  PMID: 20964769
ear tube surgery; children; postoperative analgesia; emergence agitation; intranasal fentanyl; intramuscular ketorolac
24.  A Comparative Study of Induction, Maintenance and Recovery Characteristics of Sevoflurane and Halothane Anaesthesia in Pediatric Patients (6 months to 6 years) 
Patients & Methods:
In a randomized , double blind clinical study, we studied 30 children, aged 6 months to 6 years, to compare halothane and sevoflurane anaesthesia in patients undergoing short surgical procedures under general anaesthesia. All the patients were premedicated with atropine 0.02mg kg-1and midazolam 0.1mg kg-1body weight intravenously and received inhalation induction using nitrous oxide in oxygen supplemented with either halothane (maximum inspired concentration of 5%) or sevoflurane (maximum inspired concentration of 8%). Induction was by inhalation of increasing concentrations of sevoflurane (1%) or halothane (0.5%) in the vaporizing setting after every three breaths of the patient.
Time to loss of eyelash reflex and tracheal intubation was more rapid using sevoflurane. Cardiac arrhythmias were significantly more frequent during halothane than sevoflurane anaesthesia. Psychomotor recovery was more rapid after sevoflurane anaesthesia. Children who received sevoflurane had comparatively less nausea and vomiting and the incidence of clinically important side effects was significantly less with sevoflurane anaesthesia.
We conclude that induction with sevoflurane in nitrous oxide and oxygen leads to fast loss of consciousness and provides ideal conditions for managing the airway without supplemental opioids or muscle relaxants with haemodynamic stability and is therefore a reasonable alternative to halothane for paediatric patients.
PMCID: PMC3087258  PMID: 21547175
Halothane; Sevoflurane; paediatric; children
25.  Influence of the Sevoflurane Concentration on the Occurrence of Epileptiform EEG Patterns 
PLoS ONE  2014;9(2):e89191.
Objectives and Aim
This study was performed to analyse the effects of different sevoflurane concentrations on the incidence of epileptiform EEG activity during induction of anaesthesia in children in the clinical routine.
It was suggested in the literature to use sevoflurane concentrations lower than 8% to avoid epileptiform activity during induction of anaesthesia in children.
100 children (age: 4.6±3.0 years, ASA I–III, premedication with midazolam) were anaesthetized with 8% sevoflurane for 3 min or 6% sevoflurane for 5 min in 100% O2 via face mask followed by 4% sevoflurane until propofol and remifentanil were given for intubation. EEGs were recorded continuously and were analysed visually with regard to epileptiform EEG patterns.
From start of sevoflurane until propofol/remifentanil administration, 38 patients (76%) with 8% sevoflurane had epileptiform EEG patterns compared to 26 patients (52%) with 6% (p = 0.0106). Epileptiform potentials tended to appear later in the course of the induction with 6% than with 8%. Up to an endtidal concentration of 6% sevoflurane, the number of children with epileptiform potentials was similar in both groups (p = 0.3708). The cumulative number of children with epileptiform activity increased with increasing endtidal sevoflurane concentrations. The time from start of sevoflurane until loss of consciousness was similar in patients with 8% and 6% sevoflurane (42.2±17.5 s vs. 44.9 s ±14.0 s; p = 0.4073). An EEG stage of deep anaesthesia with continuous delta waves <2.0 Hz appeared significantly earlier in the 8% than in the 6% group (64.0±22.2 s vs. 77.9±20.0 s, p = 0.0022).
The own analysis and data from the literature show that lower endtidal concentrations of sevoflurane and shorter administration times can be used to reduce epileptiform activity during induction of sevoflurane anaesthesia in children.
PMCID: PMC3935848  PMID: 24586585

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