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1.  Dexmedetomidine use in the ICU: Are we there yet? 
Critical Care  2013;17(3):320.
Expanded abstract
Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedeto midine for Long-Term Sedation Investigators: Dexmedetomidine vesus midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012, 307:1151-1160.
Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an alpha-2 agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.
The objective was to determine the efficacy of dexmedetomidine versus midazolam or propofol (preferred usual care) in maintaining sedation, reducing duration of mechanical ventilation, and improving patients' interaction with nursing care.
Two phase 3 multicenter, randomized, double-blind trials were conducted.
The MIDEX (Midazolam vs. Dexmedetomidine) trial compared midazolam with dexmedetomidine in ICUs of 44 centers in nine European countries. The PRODEX (Propofol vs. Dexmedetomidine) trial compared propofol with dexmedetomidine in 31 centers in six European countries and two centers in Russia.
The subjects were adult ICU patients who were receiving mechanical ventilation and who needed light to moderate sedation for more than 24 hours.
After enrollment, 251 and 249 subjects were randomly assigned midazolam and dexmedetomidine, respectively, in the MIDEX trial, and 247 and 251 subjects were randomly assigned propofol and dexmedetomidine, respectively, in the PRODEX trial. Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials were employed.
For each trial, investigators tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were the ability of the patient to communicate pain (measured by using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol (midazolam, n = 233, versus dexmedetomidine, n = 227; propofol, n = 214, versus dexmedetomidine, n = 223) population.
Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% confidence interval (CI) 0.97 to 1.18), and dexmedetomidine/propofol ratio in time at target sedation was 1.00 (95% CI 0.92 to 1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours, interquartile range (IQR) 67 to 337) versus midazolam (164 hours, IQR 92 to 380; P = 0.03) but not with dexmedetomidine (97 hours, IQR 45 to 257) versus propofol (118 hours, IQR 48 to 327; P = 0.24). Patient interaction (measured by using VAS) was improved with dexmedetomidine (estimated score difference versus midazolam 19.7, 95% CI 15.2 to 24.2; P <0.001; and versus propofol 11.2, 95% CI 6.4 to 15.9; P <0.001). Lengths of ICU and hospital stays and mortality rates were similar. Dexmedetomidine versus midazolam patients had more hypotension (51/247 [20.6%] versus 29/250 [11.6%]; P = 0.007) and bradycardia (35/247 [14.2%] versus 13/250 [5.2%]; P <0.001).
Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved the ability of patients to communicate pain compared with midazolam and propofol. Greater numbers of adverse effects were associated with dexmedetomidine.
PMCID: PMC3706806  PMID: 23731973
2.  Prospective Randomized Crossover Evaluation of Three Anesthetic Regimens for Painful Procedures in Children with Cancer 
The Journal of pediatrics  2012;162(1):137-141.
To identify the most effective sedation regimen for bone marrow aspiration and lumbar puncture procedures with a prospective trial of 3 combinations of sedation/analgesia.
Study design
In this double-blind crossover study, we randomly assigned 162 children with acute lymphoblastic leukemia or lymphoblastic lymphoma to receive fentanyl 1 mcg/kg, fentanyl 0.5 mcg/kg, or placebo, in addition to propofol and topical anesthetic for 355 procedures.
We found no significant differences among the three regimens in the frequency of pain (pain score >0) or severe pain (PS ≥5) during recovery, or a >20% increase in hemodynamic/respiratory variables during anesthesia. Treatment with fentanyl 1 mcg/kg was associated with a lower frequency of movement during procedure as compared with treatment with fentanyl 0.5mcg/kg (P = 0.0476) or treatment with placebo (P = 0.0545). The placebo group required longer time to recover (median, 18 minutes) as compared with the fentanyl 0.5 mcg/kg group (median, 9 minutes) (median difference 2.0, P = 0.007) and the fentanyl 1 mcg/kg (median 8 minutes), (median difference 2.0, P = 0.15). The placebo group also required larger total dose of propofol (median 5 mg/kg) as compared with that of the fentanyl 1 mcg/kg group (median, 3.5 mg/kg) and the fentanyl 0.5 mcg/kg group (median 3.5 mg/kg) (median differences 1.5, P <0.00005, in both comparisons).
The addition of fentanyl 1 mcg/kg to propofol for brief painful procedures reduces movement, propofol dose, and recovery time.
PMCID: PMC3529769  PMID: 22883421
pain; sedation; procedures; bone marrow aspiration; pediatric oncology
3.  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
4.  Remifentanil versus fentanyl for analgesia based sedation to provide patient comfort in the intensive care unit: a randomized, double-blind controlled trial [ISRCTN43755713] 
Critical Care  2003;8(1):R1-R11.
This double-blind, randomized, multicentre study was conducted to compare the efficacy and safety of remifentanil and fentanyl for intensive care unit (ICU) sedation and analgesia.
Intubated cardiac, general postsurgical or medical patients (aged ≥ 18 years), who were mechanically ventilated for 12–72 hours, received remifentanil (9 μg/kg per hour; n = 77) or fentanyl (1.5 μg/kg per hour; n = 75). Initial opioid titration was supplemented with propofol (0.5 mg/kg per hour), if required, to achieve optimal sedation (i.e. a Sedation–Agitation Scale score of 4).
The mean percentages of time in optimal sedation were 88.3% for remifentanil and 89.3% for fentanyl (not significant). Patients with a Sedation–Agitation Scale score of 4 exhibited significantly less between-patient variability in optimal sedation on remifentanil (variance ratio of fentanyl to remifentanil 1.84; P = 0.009). Of patients who received fentanyl 40% required propofol, as compared with 35% of those who received remifentanil (median total doses 683 mg and 378 mg, respectively; P = 0.065). Recovery was rapid (median time to extubation: 1.1 hours for remifentanil and 1.3 hours for fentanyl; not significant). Remifentanil patients who experienced pain did so for significantly longer during extubation (6.5% of the time versus 1.4%; P = 0.013), postextubation (10.2% versus 3.6%; P = 0.001) and post-treatment (13.5% versus 5.1%; P = 0.001), but they exhibited similar haemodynamic stability with no significant differences in adverse event incidence.
Analgesia based sedation with remifentanil titrated to response provided effective sedation and rapid extubation without the need for propofol in most patients. Fentanyl was similar, probably because the dosing algorithm demanded frequent monitoring and adjustment, thereby preventing over-sedation. Rapid offset of analgesia with remifentanil resulted in a greater incidence of pain, highlighting the need for proactive pain management when transitioning to longer acting analgesics, which is difficult within a double-blind study but would be quite possible under normal circumstances.
PMCID: PMC420059  PMID: 14975049
analgesia; analgesia based sedation; critical care; fentanyl; propofol; remifentanil; renal function; sedation
5.  Age-dependent safety analysis of propofol-based deep sedation for ERCP and EUS procedures at an endoscopy training center in a developing country 
Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography (EUS) procedures in elderly patients are on the rise, and they play an important role in the diagnosis and management of various gastrointestinal diseases. The use of deep sedation in these patients has been established as a safe and effective technique in Western countries; however, it is uncertain if the situation holds true among Asians. The present study aimed to evaluate the age-dependent safety analysis and clinical efficacy of propofol-based deep sedation (PBDS) for ERCP and EUS procedures in adult patients at a World Gastroenterology Organization (WGO) Endoscopy Training Center in Thailand.
We undertook a retrospective review of anesthesia or sedation service records of patients who underwent ERCP and EUS procedures. All procedures were performed by staff endoscopists, and all sedations were administered by anesthesia personnel in the endoscopy room.
PBDS was provided for 491 ERCP and EUS procedures. Of these, 252 patients (mean age, 45.1 + 11.1 years, range 17–65 years) were in the <65 age group, 209 patients (mean age, 71.7 + 4.3 years, range 65–80 years) were in the 65–80 year-old group, and 30 patients (mean age, 84.6 + 4.2 years, range 81–97 years) were in the >80 age group. Common indications for the procedures were pancreatic tumor, cholelithiasis, and gastric tumor. Fentanyl, propofol, and midazolam were the most common sedative drugs used in all three groups. The mean doses of propofol and midazolam in the very old patients were relatively lower than in the other groups. The combination of propofol, midazolam, and fentanyl, as well as propofol and fentanyl, were frequently used in all patients. Sedation-related adverse events and procedure-related complications were not statistically significantly different among the three groups. Hypotension was the most common complication.
In the setting of the WGO Endoscopy Training Center in a developing country, PBDS for ERCP and EUS procedures in elderly patients by trained anesthesia personnel with appropriate monitoring is relatively safe and effective. Although adverse cardiovascular events, including hypotension, in this aged group is common, all adverse events were usually transient, mild, and easily treated, with no sequelae.
PMCID: PMC3401056  PMID: 22826640
deep sedation; propofol; endoscopic retrograde cholangiopancreatography; endoscopic ultrasonography; elderly; developing country
6.  Sedation with etomidate-fentanyl versus propofol-fentanyl in colonoscopies: A prospective randomized study 
The combination of propofol-fentanyl for sedation during colonoscopy is characterized by high prevalence of side effects. Etomidate-fentanyl provides fewer hemodynamic and respiratory complications. The aim of our study was to compare the safety and efficacy of propofol-fentanyl and etomidate-fentanyl for conscious sedation in elective colonoscopy.
This double-blind clinical trial was conducted on 90 patients aged between 18- 55 years old who were candidates for elective colonoscopy. Patients were randomized to receive sedation with fentanyl plus propofol or etomidate. Two minutes after injecting 1 micro/kg of fentanyl, the patients received 0.5mg/kg propofol by infusion (25 µ/kg/min) or 0.1 mg/kg etmoidate (15 µ/kg/min). Pulse rate, mean arterial blood pressure, respiratory rate, and saturation of peripheral oxygen (SPO2) were monitored. In addition, the patient and colonoscopist satisfaction, the recovery time, sedation and pain score in both groups were assessed.
Sedation score in propofol group was higher. Pain score as well as the physician and patient satisfaction showed no significant difference between the two study groups. Hemodynamic changes and arterial saturation were the same in both groups. The duration of recovery was 1.27±0.82 minutes in the etomidate group; versus 2.57±2.46 minutes in the propofol group (P=0.001). Recovery time in the etmoid group was 2.68±3.14 minutes and in the propofol group was 5.53±4.67 minutes (p=0.001).
The combination of fentanyl and etomidate provides an acceptable alternative to sedation with fentanyl and propofol with the advantage of significantly faster recovery time, in the outpatient setting.
PMCID: PMC4478113  PMID: 26221491
Propofol; Etomidate; Colonoscopy; Sedation
7.  The median effective concentration (EC50) of propofol with different doses of fentanyl during colonoscopy in elderly patients 
BMC Anesthesiology  2016;16:24.
Propofol and fentanyl are the most widely administered anesthesia maintaining drugs during colonoscopy. In this study, we determined the median effective concentration (EC50) of propofol required for colonoscopy in elderly patients, and the purpose of this study was to describe the pharmacodynamic interaction between fentanyl and propofol when used in combination for colonoscopy in elderly patients.
Ninety elderly patients scheduled for colonoscopy were allocated into three groups in a randomized, double-blinded manner as below, F0.5 group (0.5 μ−1 fentanyl), F1.0 group (1.0 μ−1 fentanyl) and saline control group. Anaesthesia was achieved by target-controlled infusion of propofol (Marsh model, with an initial plasma concentration of 2.0 μ−1) and fentanyl. Colonoscopy was started 3 min after the injection of fentanyl. The EC50 of propofol for colonoscopy with different doses of fentanyl was measured by using an up-and-down sequential method with an adjacent concentration gradient at 0.5 μ−1 to inhibit purposeful movements. Anaesthesia associated adverse events and recovery characters were also recorded.
The EC50 of propofol for colonoscopy in elderly patients were 2.75 μ−1 (95 % CI, 2.50–3.02 μ−1) in F0.5 group, 2.05 μ−1 (95 % CI, 1.98–2.13 μ−1) in F1.0 group and 3.08 μ−1 (95 % CI, 2.78–3.42 μ−1) in control group respectively (P < 0.05). Patients in the F1.0 group had a significantly longer awake time and length of hospital stay than those in control group (P < 0.05).
Increasing doses of fentanyl up to 1.0 μ−1 reduces the propofol EC50 required for elderly patients undergoing colonoscopy, and there was no significant difference in anaesthesia associated adverse events but prolonged awake and discharge time.
Trial registration
Chinese Clinical Trial Registry ChiCTR15006368. Date of registration: May 3, 2015.
PMCID: PMC4840854  PMID: 27106691
EC50; Propofol; Fentanyl; Elderly patients
8.  Comparison of Propofol, Propofol-Remifentanil, and Propofol-Fentanyl Administrations with Each Other Used for the Sedation of Patients to Undergo ERCP 
BioMed Research International  2015;2015:465465.
Introduction. Using single anesthetic agent in endoscopic retrograde cholangiopancreatography (ERCP) may lead to inadequate analgesia and sedation. To achieve the adequate analgesia and sedation the single anesthetic agent doses must be increased which causes undesirable side effects. For avoiding high doses of single anesthetic agent nowadays combination with sedative agents is mostly a choice for analgesia and sedation for ERCP. Aim. The aim of this study is to investigate the effects of propofol alone, propofol + remifentanil, and propofol + fentanyl combinations on the total dose of propofol to be administered during ERCP and on the pain scores after the process. Materials and Method. This randomized study was performed with 90 patients (ASA I-II-III) ranging between 18 and 70 years of age who underwent sedation/analgesia for elective ERCP. The patients were administered only propofol (1.5 mg/kg) in Group Ι, remifentanil (0.05 μg/kg) + propofol (1.5 mg/kg) combination in Group II, and fentanyl (1 μg/kg) + propofol (1.5 mg/kg) combination in Group III. All the patients' sedation levels were assessed with the Ramsey Sedation Scale (RSS). Their recovery was assessed with the Aldrete and Numerical Rating Scale Score (NRS) at 10 min intervals. Results. The total doses of propofol administered to the patients in the three groups in this study were as follows: 375 mg in Group I, 150 mg in Group II, and 245 mg in Group III. Conclusion. It was observed that, in the patients undergoing ERCP, administration of propofol in combination with an opioid provided effective and reliable sedation, reduced the total dose of propofol, increased the practitioner satisfaction, decreased the pain level, and provided hemodynamic stability compared to the administration of propofol alone.
PMCID: PMC4631853  PMID: 26576424
9.  Retrospective Review of Propofol Dosing for Procedural Sedation in Pediatric Patients 
The purpose of this study was to determine the total propofol dose (mg/kg) for non-emergent pediatric procedural sedation and evaluate dosing differences with regard to a patient's sex, age, and body mass index. Adverse events were recorded and evaluated to determine whether certain patient groups were at a higher risk than others.
This study was a retrospective observational pilot study including patients 0 to 18 years of age admitted between January 2008 and November 2009 for non-emergent gastrointestinal endoscopic procedures or radiologic imaging, who received propofol for procedural sedation. Data gathered included sex, age, height, weight, chronic medical conditions and medication use, concomitant anesthetic gas, preprocedure midazolam, procedure length, propofol dose in mg/kg, other medications administered during procedure, and adverse events that occurred. Comparisons between adverse event groups and categories of baseline characteristics were made using the Wilcoxon signed-rank, Kruskal-Wallis nonparametric and Pearson's chisquare tests, as appropriate.
A total of 101 patients met inclusion criteria and were included in the analysis. The mean dose of propofol required for female patients was 3.7 mg/kg versus 3.4 mg/kg for males (p=0.3). The mean dose of propofol for patients ≤9 years, 10 to 12 years, and >12 years was 3.2, 3.9, and 3.9 mg/kg, respectively (p=0.25). The mean dose of propofol for underweight, healthy weight, overweight, and obese patients was 4.2, 3.9, 3.6, and 2.6 mg/kg, respectively (p=0.38). Hypotension occurred in 42.6% of patients, and bradycardia occurred in 13.9% of patients.
There were no differences in dose requirements based on sex or age. The difference in dosing between different body weight categories was not statistically significant. The dose of propofol was higher in patients that experienced bradycardia and hypotension, but there was no statistical significance. Given the above, future studies with larger sample sizes should be conducted to establish if statistical significance exists.
PMCID: PMC3526928  PMID: 23258967
computed tomography; endoscopy; gastrointestinal; magnetic resonance imaging; pediatrics; propofol
10.  Evaluation of propofol anesthesia in morbidly obese children and adolescents 
BMC Anesthesiology  2013;13:8.
Poor characterization of propofol pharmacokinetics and pharmacodynamics in the morbidly obese (MO) pediatric population poses dosing challenges. This study was conducted to evaluate propofol total intravenous anesthesia (TIVA) in this population.
After IRB approval, a prospective study was conducted in 20 MO children and adolescents undergoing laparoscopic surgery under clinically titrated propofol TIVA. Propofol doses/infusion rates, hemodynamic variables, times to induction and emergence, and postoperative occurrence of respiratory adverse events (RAE) were recorded, along with intraoperative blinded Bispectral Index/BIS and postoperative Ramsay sedation scores (RSS). Study subjects completed awareness questionnaires on postoperative days 1 and 3. Propofol concentrations were obtained at predetermined intra- and post-operative time points.
Study subjects ranged 9 – 18 years (age) and 97 - 99.9% (BMI for age percentiles). Average percentage variability of hemodynamic parameters from baseline was ≈ 20%. Patients had consistently below target BIS values (BIS < 40 for >90% of maintenance phase), delayed emergence (25.8 ± 22 minutes), increased somnolence (RSS ≥ 4) in the first 30 minutes of recovery from anesthesia and 30% incidence of postoperative RAE, the odds for which increased by 14% per unit increase in BMI (p ≤ 0.05). Mean propofol concentration was 6.2 mg/L during maintenance and 1.8 mg/L during emergence from anesthesia.
Our findings indicate clinical overestimation of propofol requirements and highlight the challenges of clinically titrated propofol TIVA in MO adolescents. In this setting, it may be advantageous to titrate propofol to targeted BIS levels until more accurate weight-appropriate dosing regimens are developed, to minimize relative overdosing and its consequences.
PMCID: PMC3644256  PMID: 23602008
Morbidly obese; Bariatric; Propofol; Total intravenous anesthesia; Bispectral index; Anesthetic depth; Pediatric; Adolescents
11.  Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study 
Critical Care  2014;18(3):R122.
Midazolam and propofol used alone for long-term sedation are associated with adverse effects. Sequential use may reduce the adverse effects, and lead to faster recovery, earlier extubation and lower costs. This study evaluates the effects, safety, and cost of midazolam, propofol, and their sequential use for long-term sedation in critically ill mechanically ventilated patients.
A total of 135 patients who required mechanical ventilation for >3 days were randomly assigned to receive midazolam (group M), propofol (group P), or sequential use of both (group M-P). In group M-P, midazolam was switched to propofol until the patients passed the spontaneous breathing trial (SBT) safety screen. The primary endpoints included recovery time, extubation time and mechanical ventilation time. The secondary endpoints were pharmaceutical cost, total cost of ICU stay, and recollection to mechanical ventilation-related events.
The incidence of agitation following cessation of sedation in group M-P was lower than group M (19.4% versus 48.7%, P = 0.01). The mean percentage of adequate sedation and duration of sedation were similar in the three groups. The recovery time, extubation time and mechanical ventilation time of group M were 58.0 (interquartile range (IQR), 39.0) hours, 45.0 (IQR, 24.5) hours, and 192.0 (IQR, 124.0) hours, respectively; these were significantly longer than the other groups, while they were similar between the other two groups. In the treatment-received analysis, ICU duration was longer in group M than group M-P (P = 0.016). Using an intention-to-treat analysis and a treatment-received analysis, respectively, the pharmaceutical cost of group M-P was lower than group P (P <0.01) and its ICU cost was lower than group M (P <0.01; P = 0.015). The proportion of group M-P with unbearable memory of the uncomfortable events was lower than in group M (11.7% versus 25.0%, P <0.01), while the proportion with no memory was similar (P >0.05). The incidence of hypotension in group M-P was lower than group (P = 0.01).
Sequential use of midazolam and propofol was a safe and effective sedation protocol, with higher clinical effectiveness and better cost-benefit ratio than midazolam or propofol used alone, for long-term sedation of critically ill mechanically ventilated patients.
Trial registration
Current Controlled Trials ISRCTN01173443. Registered 25 February 2014.
PMCID: PMC4095601  PMID: 24935517
12.  Deep sedation for endoscopic retrograde cholangiopancreatography: a comparison between clinical assessment and NarcotrendTM monitoring 
Moderate to deep sedation is generally used for endoscopic retrograde cholangiopancreatography (ERCP). The depth of sedation is usually judged by clinical assessment and electroencephalography-guided monitoring. The aim of this study was to compare the clinical efficacy of clinical assessment and NarcotrendTM monitoring during deep-sedated ERCP.
One hundred patients who underwent ERCP in a single year were randomly assigned to either group C or group N. Patients in group C (52) were sedated using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale. Patients in group N (48) were sedated using the NarcotrendTM system. The MOAA/S scale 1 or 2 and the NarcotrendTM index 47–56 to 57–64 were maintained during the procedure. The primary outcome variable of the study was the successful completion of the endoscopic procedure. The secondary outcome variables were the total dose of propofol used during the procedure, complications during and immediately after procedure, and recovery time.
All endoscopies were completed successfully. The mean total dose of propofol in group C was significantly lower than that in group N. However, the mean dose of propofol, expressed as dose/kg or dose/kg/h in both groups, was not significantly different (P = 0.497, 0.136). Recovery time, patient tolerance and satisfaction, and endoscopist satisfaction were comparable between the two groups. All sedation-related adverse events during and immediately after the procedure, such as hypotension, hypertension, tachycardia, bradycardia, transient hypoxia, and upper airway obstruction, in group C (62.2%) were significantly higher than in group N (37.5%) (P = 0.028).
Clinical assessment and NarcotrendTM-guided sedation using propofol for deep sedation demonstrated comparable propofol dose and recovery time. Both monitoring systems were equally safe and effective. However, the NarcotrendTM-guided sedation showed lower hemodynamic changes and fewer complications compared with the clinical assessment-guided sedation.
PMCID: PMC3417873  PMID: 22915929
deep sedation; endoscopic retrograde cholangiopancreatography; clinical assessment; NarcotrendTM monitoring
13.  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
14.  A Phase 1c Trial Comparing the Efficacy and Safety of a New Aqueous Formulation of Alphaxalone with Propofol 
Anesthesia and Analgesia  2015;121(4):914-924.
Phaxan™ (PHAX, Chemic Labs, Canton, MA) is an aqueous solution of 10 mg/mL alphaxalone and 13% 7-sulfobutylether β-cyclodextrin (betadex). In preclinical studies, PHAX is a fast onset–offset IV anesthetic like propofol, but causes less cardiovascular depression. This first-in-man study was designed to find the anesthetic dose of PHAX and to compare it with an equivalent dose of propofol for safety, efficacy, and quality of recovery from anesthesia and sedation.
The study adhered to compliance with Good Clinical Practices regulations (clinical trials registry number, ACTRN12611000343909). This randomized, double-blind study compared PHAX and propofol using a Bayesian algorithm to determine dose equivalence for effects on the bispectral index (BIS). Male volunteers, ASA physical status I, gave written informed consent (n = 12 per group; PHAX or propofol). Parameters assessed for 80 minutes after drug injection (single bolus dose) were pain on injection, involuntary movement, BIS, blood pressure, need for airway support, and, as measures of recovery from sedation, the Richmond Agitation and Sedation Scale and the Digit Symbol Substitution Test. Arterial blood was withdrawn for biochemistry, hematology, and complement levels.
No subject complained of pain on injection with PHAX, whereas 8 of the 12 subjects given propofol did. Nine PHAX and 8 propofol subjects reached BIS values of ≤50: median (interquartile range [IQR]) mg/kg dose = 0.5 (0.5–0.6) for PHAX and 2.9 (2.4–3.0) for propofol. The lowest median BIS reached was 27 to 28 for both agents with no significant differences between them for timing of onset and recovery of BIS. The concomitant median changes in systolic and diastolic blood pressures were −11% vs −19% for systolic and −25% vs −37% for diastolic in PHAX- and propofol-treated subjects, respectively. Nine of the 12 propofol-treated subjects and none of 12 PHAX-treated subjects required airway support. For subjects reaching an equivalent BIS of ≤50: a Richmond Agitation and Sedation Scale score of 0 was reached at a median of 5 (IQR, 5–10) and 15 (IQR, 10–20) minutes after PHAX and propofol, respectively; BIS returned to 90 at a mean of 21 (SD, 10.1) and 21 (SD, 9.2) minutes after PHAX and propofol, respectively; and Digit Symbol Substitution Test scores returned to predrug injection values at median of 50 (IQR, 35–72.5) and 42.5 (IQR, 35–76.3) minutes after PHAX and propofol, respectively. There was no increase in C3 and C4 complement fractions after either drug.
PHAX causes fast-onset, short-duration anesthesia with fast cognitive recovery similar to propofol, but with less cardiovascular depression, or airway obstruction and no pain on injection.
Published ahead of print July 29, 2015
PMCID: PMC4564024  PMID: 26226029
15.  Addition of sub-anaesthetic dose of ketamine reduces gag reflex during propofol based sedation for upper gastrointestinal endoscopy: A prospective randomised double-blind study 
Indian Journal of Anaesthesia  2014;58(4):436-441.
Background and Aims:
Gag reflex is unwanted during upper gastrointestinal endoscopy (UGIE). Experimental studies have demonstrated that N-methyl-D-aspartate receptor antagonism prevents gag reflex. We conducted a study to determine if sub-anaesthetic doses of ketamine, added to propofol, reduce the incidence of gag reflex.
This prospective, randomised, double-blind and placebo-controlled study was done in a tertiary care hospital. A total of 270 patients undergoing UGIE, were randomised to propofol (P) group (n = 135) or propofol plus ketamine (PK) group (n = 135). All patients received propofol boluses titrated to Ramsay sedation score of not <4. Patients in PK group in addition received ketamine, 0.15 mg/kg immediately before the first-propofol dose. Top-up doses of propofol were given as required. Stata 11 software (StataCorp.) was used to calculate the proportion of patients with gag reflex and the corresponding relative risk. Propofol consumed and time to recovery in the two groups was compared using Student's t-test and Cox proportional hazards regression respectively.
Significantly, fewer patients in the PK group had gag reflex compared to the P group (3 vs. 23, risk ratio = 0.214, 95% confidence interval [CI], 0.07-0.62; P = 0.005). The incidence of hypotension (6 vs. 16, risk ratio = 0.519, 95% CI = 0.25-1.038; P = 0.06), number of required airway manoeuvres (4 vs. 19, risk ratio = 0.32, 95% CI = 0.13-0.74; P = 0.014), median time to recovery (4 min vs. 5 min, hazard ratio = 1.311, 95% CI = 1.029-1.671; P = 0.028) and propofol dose administered (152 mg vs. 167 mg, 95% CI = 4.74-24.55; P = 0.004) was also less in the PK group compared to the P group.
Ketamine in sub-anaesthetic dose decreases gag reflex during UGIE.
PMCID: PMC4155289  PMID: 25197112
Endoscopy; gag reflex; ketamine
16.  The safety and efficacy of alfentanil-based induction in bronchoscopy sedation 
Medicine  2016;95(43):e5101.
Alfentanil in combination with propofol produces a synergistic sedative effect in patients undergoing flexible bronchoscopy (FB). However, the use of this combination is controversial due to the risk of cardiopulmonary depression. The aim of this study was to evaluate the proper induction regimen of alfentanil in propofol target-controlled infusion for FB sedation.
One hundred seventy-three patients were assigned randomly into 5 regimens: Group 1 and 2, alfentanil 2.5 and 5 μg/kg, respectively, immediately before propofol administration; Group 3 and 4, alfentanil 2.5 and 5 μg/kg, respectively, 2 minutes before propofol administration; and Group 5, propofol administration alone to achieve the observer assessment of alertness and sedation scale 3∼2. The bronchoscopists, physicians in charge of sedation, and patients were blind to the regimens. Adverse events, drug dose, induction, procedure and recovery time, cough severity, and propofol injection related pain were recorded.
The patients in groups 2 and 4 required a lower dose of propofol (P = 0.031 and 0.019, respectively) and shorter time (P = 0.035 and 0.010) than group 5 for induction. Patients in group 2 experienced more hypoxemia than those in group 5 during induction (P = 0.031). The physician in charge of sedation scored a lower severity of cough in the patients in group 4 than in groups 3 and 5. There were no differences in terms of propofol injection related pain among the groups.
Alfentanil 5 μg/kg given immediately before propofol infusion cannot be recommended. Further study is required to define conclusions about alfentanil 2.5 and 5 μg/kg because of the low power rating of subgroup in the present study.
PMCID: PMC5089092  PMID: 27787363
alfentanil; bronchoscopy; hypotension; hypoxemia; propofol
17.  Prevention of Propofol Injection Pain in Children: A Comparison of Pretreatment with Tramadol and Propofol-Lidocaine Mixture 
Background: The pain on propofol injection is considered to be a common and difficult to eliminate problem in children. In this study, we aimed to compare the efficacy of pretreatment with tramadol 1 propofol-lidocaine 20 mg mixture for prevention of propofol induced pain in children.
Methods: One hundred and twenty ASA I-II patients undergoing orthopedic and otolaryngological surgery were included in this study and were divided into three groups with random table numbers. Group C (n=39) received normal saline placebo and Group T (n=40) received 1 tramadol 60 sec before propofol (180 mg 1% propofol with 2 ml normal saline) whereas Group L (n=40) received normal saline placebo before propofol-lidocaine mixture (180 mg 1% propofol with 2 ml %1 lidocaine). One patient in Group C was dropped out from the study because of difficulty in inserting an iv cannula. Thus, one hundred and nineteen patients were analyzed for the study. After given the calculated dose of propofol, a blinded observer assessed the pain with a four-point behavioral scale.
Results: There were no significant differences in patient characteristics and intraoperative variables (p>0.05) except intraoperative fentanyl consumption and analgesic requirement one hr after surgery among the groups (p<0.05). Both tramadol 1 and lidocaine 20 mg mixture significantly reduced propofol pain when compared with control group. Moderate and severe pain were found higher in control group (p<0.05). The incidence of overall pain was 79.4% in the control group, 35% in tramadol group, 25% in lidocaine group respectively (p<0.001).
Conclusions: Pretreatment with tramadol 60 sec before propofol injection and propofol-lidocaine mixture were significantly reduced propofol injection pain when compared to placebo in children.
PMCID: PMC3427954  PMID: 22927775
tramadol; lidocaine; propofol; pain; children.
18.  Intravenous infusion of ketamine-propofol can be an alternative to intravenous infusion of fentanyl-propofol for deep sedation and analgesia in paediatric patients undergoing emergency short surgical procedures 
Indian Journal of Anaesthesia  2012;56(2):145-150.
Paediatric patients often present with different painful conditions that require immediate surgical interventions. Despite a plethora of articles on the ketamine–propofol combination, comprehensive evidence regarding the suitable sedoanalgesia regime is lacking due to heterogeneity in study designs.
This prospective, randomized, double-blind, active–controlled trial was conducted in 100 children, of age 3–14 years, American Society of Anesthesiologist physical status IE-IIE, posted for emergency short surgical procedures. Patients were randomly allocated to receive either 2 mL of normal saline (pre-induction) plus calculated volume of drug from the 11 mL of ketamine–propofol solution for induction (group PK, n=50) or fentanyl 1.5 μg/kg diluted to 2 mL with normal saline (pre-induction) plus calculated volume of drug from the 11 mL of propofol solution for induction (group PF, n=50). In both the groups, the initial bolus propofol 1 mg/kg i.v. (assuming the syringes contained only propofol, for simplicity) was followed by adjusted infusion to achieve a Ramsay Sedation Scale score of six. Mean arterial pressure (MAP) was the primary outcome measurement.
Data from 48 patients in group PK and 44 patients in group PF were available for analysis. Hypotension was found in seven patients (14.6%) in group PK compared with 17 (38.6%) patients in group PF (P=0.009). Intraoperative MAP was significantly lower in group PF than group PK when compared with baseline.
The combination of low-dose ketamine and propofol is more effective and a safer sedoanalgesia regimen than the propofol–fentanyl combination in paediatric emergency short surgical procedures in terms of haemodynamic stability and lesser incidence of apnoea.
PMCID: PMC3371489  PMID: 22701205
Drug combinations; fentanyl; ketamine; paediatric emergency; procedural sedation; propofol
19.  Prevalence of Delirium and Coma In Mechanically Ventilated Patients Sedated With Dexmedetomidine or Propofol 
Pharmacy and Therapeutics  2016;41(7):442-445.
In a retrospective review, the prevalence of delirium did not differ among intensive care unit patients who received either dexmedetomidine or propofol alone for 24 hours or more. Propofol was linked with more coma and shorter hospital stays.
To assess the prevalence of delirium and coma in mechanically ventilated patients sedated with dexmedetomidine or propofol alone; to evaluate the hospital length of stay for both treatment groups; and to evaluate the level of sedation, adverse effects, and hospital outcomes.
Medical records were reviewed retrospectively for patients who were admitted to the medical or surgical intensive care units (ICUs) in a 591-bed teaching hospital and who received either dexmedetomidine or propofol alone for 24 hours or more for sedation.
A total of 111 patients were included in the study, with 56 patients in the dexmedetomidine group and 55 patients in the propofol group. Results of the analysis showed that the propofol group had a higher prevalence of coma (43.6% versus 12.5%; P < 0.001). Dexmedetomidine patients had a longer median hospital length of stay of 23.5 days (interquartile range [IQR], 11.5–39.5 days) versus 15.0 days (IQR, 7.0–24.0 days; P = 0.01). The rates of delirium were similar in both groups, with 16% in dexmedetomidine-treated patients versus 20% in propofol-treated patients (P = 0.63).
No difference in the prevalence of delirium was found when comparing the dexmedetomidine- and propofol-treated groups. Propofol was associated with more coma and oversedation; dexmedetomidine was associated with longer time to extubation, longer length of stay in the ICU, and longer hospital length of stay.
PMCID: PMC4927019  PMID: 27408521
delirium; coma; mechanical ventilation; sedation; dexmedetomidine; propofol; intensive care
20.  Cardiopulmonary Safety of Propofol Versus Midazolam/Meperidine Sedation for Colonoscopy: A Prospective, Randomized, Double-Blinded Study 
Different levels of pharmacological sedation ranging from minimal to general anesthesia are often used to increase patient tolerance for a successful colonoscopy. However, sedation increases the risk of respiratory depression and cardiovascular complications during colonoscopy.
We aimed to compare the propofol and midazolam/meperidine sedation methods for colonoscopy procedures with respect to cardiopulmonary safety, procedure-related times, and patient satisfaction.
Patients and Methods:
This was a prospective, randomized, double-blinded study, in which 124 consecutive patients undergoing elective outpatient diagnostic colonoscopies were divided into propofol and midazolam/meperidine sedation groups (n: 62, m/f ratio: 26/36, mean age: 46 ± 15 for the propofol group; n: 62, m/f ratio: 28/34, mean age: 49 ± 15 for the midazolam/meperidine group) by computer-generated randomization. The frequency of cardiopulmonary events (hypotension, bradycardia, hypoxemia), procedure-related times (duration of colonoscopy, time to cecal intubation, time to ileal intubation, awakening time, and time to hospital discharge) and patients’ evaluation results (pain assessment, quality of sedation, and recollection of procedure) were compared between the groups.
There were no statistically significant differences between the two groups with respect to demographic and clinical characteristics of the patients, the frequency of hypotension, hypoxemia or bradycardia, cecal and ileal intubation times, and the duration of colonoscopy. The logistic regression analysis indicated that the development of cardiopulmonary events was not associated with the sedative agent used or the characteristics of the patients. The time required for the patient to be fully awake and the time to hospital discharge was significantly longer in the propofol group (11 ± 8 and 37 ± 11 minutes, respectively) than the midazolam/meperidine group (8 ± 6 and 29 ± 12 minutes, respectively) (P = 0.009 and P < 0.001, respectively). The patient satisfaction rates were not significantly different between the groups; however, patients in the propofol group experienced more pain than patients in the midazolam/meperidine group (VAS score: 0.31 ± 0.76 vs. 0 ± 0; P = 0.002).
Midazolam/meperidine and propofol sedation for colonoscopy have similar cardiopulmonary safety profiles and patient satisfaction levels. Midazolam/meperidine can be preferred to propofol sedation due to a shorter hospital length of stay and better analgesic activity.
PMCID: PMC4329962  PMID: 25763217
Colonoscopy; Propofol; Midazolam; Randomized Controlled Trial
21.  Comparitive Evaluation of Propofol and Midazolam as Conscious Sedatives in Minor Oral Surgery 
The objective of the study was to assess the efficacy of propofol and midazolam as an intravenous sedative agent in minor oral surgical procedures in terms of: (a) the onset of action, (b) heart rate, (c) oxygen saturation, (d) systolic and diastolic blood pressure, (e) respiratory rate, (f) pain during the injection of sedative agent, (g) recovery period, (h) side effects, (i) patient’s cooperation during the surgery.
This was a double blind randomized study in which one group of 20 patients received propofol with the induction dose of 0.5 mg/kg and 50 μg/kg/min which was administered by syringe infusion pump as a maintenance dose and the other group received midazolam in a single dose of 75 μg/kg and no maintenance dose was given, instead 5 % dextrose was administered by syringe infusion pump at the rate of 50 μg/kg/min. Since propofol was milky white in colour, a green cloth was covered over the infusion pump in all cases. The surgeon, assistants and observers were blind about the medications which would be given to the patient for sedation. After the administration of the sedative, local anesthesia was achieved with 2 % lignocaine hydrochloride.
The onset of action in propofol group was significant as onset of action was faster. The maximum increase in heart rate in propofol group was at 10 min intraoperatively (Mean ± 80.40 ± 12.73) and that in midazolam group was at 15 min intraoperatively (Mean 79.25 ± 13.44). Post operatively the heart rate decreased near to the baseline value in both the groups. The average oxygen saturation before induction in propofol group was 99.7 ± 0.73 % and that of midazolam group was 99.15 ± 01.31 P = 0.314. None of the patients in this study developed apnea. The systolic blood pressure (Mean ± SD) before induction in both the groups decreased from the baseline value after the administration of sedatives. The diastolic blood pressure (Mean ± SD) before induction in both the groups decreased from the baseline value after the administration of sedatives and the decreased diastolic blood pressure was maintained throughout the procedure. The respiratory rate (Mean ± SD) before induction in both the groups decreased from the baseline value after the administration of sedatives. The decreased respiratory rate remained throughout the surgical procedure. Pain during the injection of the sedatives was reported by nine patients (45 %) in the propofol group whereas none of the patients in midazolam group complained of pain during the injection. This is statistically significant (P = 0.001). The recovery time (Mean ± SD) in propofol group was 22.50 ± 3.04 (range 15–25 min) and that in midazolam group was 33.75 ± 3.93 (range 30–40 min), which was statistically significant (P < 0.001). Patients in the propofol group were significantly less co-operative than midazolam group at both 10 and 25 min intra operatively.
The design of the present study permitted qualitative assessment of propofol and midazolam as sedative agents in minor oral surgical procedures. The ideal anesthetic agent should provide rapid onset of action, profound intra operative amnesia while ensuring rapid recovery without much complications. There were no significant differences in either patient demographics or surgical characteristics between the two groups. The propofol group was less co-operative than midazolam group. Pain during the injection of sedative was a significant adverse effect in the propofol group. Cardiovascular parameters remained stable throughout the procedure in both study groups and no intervention was required. However recovery and onset of action was faster in the propofol group as compared with the midazolam group.
PMCID: PMC4510082  PMID: 26225076
Propofol; Midazolam; Minor oral surgery; Day care surgery
22.  Evaluating the effects of dexmedetomidine compared to propofol as adjunctive therapy in patients with alcohol withdrawal 
In severe alcohol withdrawal (AW), benzodiazepines may be inadequate to control symptoms. In many situations, benzodiazepine dosing escalates despite no additional efficacy and introduces potential toxicities. Severe cases of AW may require additional agents to control symptoms. Case reports and studies have shown benefits with dexmedetomidine and propofol in severe AW, but these agents have not been compared with one another. This study compares the effects of dexmedetomidine and propofol on benzodiazepine and haloperidol utilization in patients with AW.
A retrospective chart review was completed on 41 patients with AW who received adjunctive dexmedetomidine or propofol. The primary objective was to compare benzodiazepine and haloperidol utilization before and after initiation of dexmedetomidine or propofol. Secondary measures included AW and sedation scoring, analgesic use, intensive care unit length of stay, rates of intubation, and adverse events.
Among the dexmedetomidine and propofol groups, significant reductions in benzodiazepine (P≤0.0001 and P=0.043, respectively) and haloperidol (P≤0.0001 and P=0.026, respectively) requirements were observed. These reductions were comparable between groups (P=0.933 and P=0.465, respectively). A trend toward decreased intensive care unit length of stay in the dexmedetomidine group (123.6 hours vs 156.5 hours; P=0.125) was seen. Rates of intubation (14.7% vs 100%) and time of intubation (19.9 hours vs 97.6 hours; P=0.002) were less in the dexmedetomidine group. Incidence of hypotension was 17.6% in the dexmedetomidine group vs 28.5% in the propofol group. Incidence of bradycardia was 17.6% in the dexmedetomidine group vs 0% in the propofol group. No differences were observed in other secondary outcomes.
In patients with severe AW who require sedation, both dexmedetomidine and propofol have unique and advantageous properties. Both agents appear to have equivalent efficacy in reducing AW-related symptoms and benzodiazepine and haloperidol requirements. These results should be validated in a larger, prospective trial.
PMCID: PMC4222895  PMID: 25382987
dexmedetomidine; propofol; benzodiazepines; alcohol; withdrawal
23.  Pharmacokinetics, induction of anaesthesia and safety characteristics of Propofol 6% SAZN vs Propofol 1% SAZN and Diprivan®-10 after bolus injection 
In order to avoid the potential for elevated serum lipid levels as a consequence of long term sedation with propofol, a formulation of propofol 6% in Lipofundin® MCT/LCT 10% (Propofol 6% SAZN) has been developed. The pharmacokinetics, induction of anaesthesia and safety characteristics of this new formulation were investigated after bolus injection and were compared with the commercially available product (propofol 1% in Intralipid® 10%, Diprivan®-10) and propofol 1% in Lipofundin® MCT/LCT 10% (Propofol 1% SAZN).
In a randomised double-blind study, 24 unpremedicated female patients received an induction dose of propofol of 2.5 mg kg−1 over 60 s which was followed by standardized balanced anaesthesia. The patients were randomized to receive propofol as Propofol 6% SAZN, Propofol 1% SAZN or Diprivan®-10.
For all formulations the pharmacokinetics were adequately described by a tri-exponential equation, as the propofol concentrations collected early after the injection suggested an additional initial more rapid phase. The average values for clearance (CL), volume of distribution at steady-state (Vd,ss), elimination half-life (t1/2,z) and distribution half-life (t1/2,λ2) observed in the three groups were 32±1.5 ml kg−1 min−1, 2.0±0.18 l kg−1, 95±5.6 min and 3.4±0.20 min, respectively (mean±s.e.mean, n = 24) and no significant differences were noted between the three formulations (P > 0.05). The half-life of the additional initial distribution phase (t1/2,λ1) in all subjects ranged from 0.1 to 0.6 min. Anaesthesia was induced successfully and uneventfully in all cases, and the quality of induction was adequate in all 24 patients. The induction time did not vary between the three formulations and the average induction time observed in the three groups was 51±1.3 s which corresponded to an induction dose of propofol of 2.1±0.06 mg kg−1 (mean±s.e.mean, n = 24). The percentage of patients reporting any pain on injection did not vary between the formulations and was 17% for the three groups. No postoperative phlebitis or other venous sequelae of the vein used for injection occurred in any of the patients at recovery of anaesthesia nor after 24 h.
From the above results, we conclude that the alteration of the type of emulsion and the higher concentration of propofol in the new parenteral formulation of propofol does not affect the pharmacokinetics and induction characteristics of propofol, compared with the currently available product. Propofol 6% SAZN can be administered safely and has the advantage of a reduction of the load of fat and emulsifier which may be preferable when long term administration of propofol is required.
PMCID: PMC2014258  PMID: 10383543
anaesthetics i.v.; propofol; pharmacokinetics; induction characteristics; pharmacology; emulsion formulation
24.  Bispectral index monitoring as an adjunct to nurse-administered combined sedation during endoscopic retrograde cholangiopancreatography 
AIM: To determine whether bispectral index (BIS) monitoring is useful for propofol administration for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP).
METHODS: Fifty-nine consecutive patients with a variety of reasons for ERCP who underwent the procedure at least twice between 1 July 2010 and 30 November 2010. This was a randomized cross-over study, in which each patient underwent ERCP twice, once with BIS monitoring and once with control monitoring. Whether BIS monitoring was done during the first or second ERCP procedure was random. Patients were intermittently administered a mixed regimen including midazolam, pethidine, and propofol by trained nurses. The nurse used a routine practice to monitor sedation using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale or the BIS monitoring. The total amount of midazolam and propofol used and serious side effects were compared between the BIS and control groups.
RESULTS: The mean total propofol dose administered was 53.1 ± 32.2 mg in the BIS group and 54.9 ± 30.8 mg in the control group (P = 0.673). The individual propofol dose received per minute during the ERCP procedure was 2.90 ± 1.83 mg/min in the BIS group and 3.44 ± 2.04 mg in the control group (P = 0.103). The median value of the MOAA/S score during the maintenance phase of sedation was comparable for the two groups. The mean BIS values throughout the procedure (from insertion to removal of the endoscope) were 76.5 ± 8.7 for all 59 patients in using the BIS monitor. No significant differences in the frequency of < 80% oxygen saturation, hypotension (< 80 mmHg), or bradycardia (< 50 beats/min) were observed between the two study groups. Four cases of poor cooperation occurred, in which the procedure should be stopped to add the propofol dose. After adding the propofol, the procedure could be conducted successfully (one case in the BIS group, three cases in the control group). The endoscopist rated patient sedation as excellent for all patients in both groups. All patients in both groups rated their level of satisfaction as high (no discomfort). During the post-procedural follow-up in the recovery area, no cases of clinically significant hypoxic episodes were recorded in either group. No other postoperative side effects related to sedation were observed in either group.
CONCLUSION: BIS monitoring trend to slighlty reduce the mean propofol dose. Nurse-administered propofol sedation under the supervision of a gastroenterologist may be considered an alternative under anesthesiologist.
PMCID: PMC3501778  PMID: 23180950
Conscious sedation; Bispectral index monitors; Pancreatic neoplasm; Endoscopic retrograde cholangiopancreatography
25.  Conscious Sedation and Emergency Department Length of Stay: A Comparison of Propofol, Ketamine, and Fentanyl/Versed 
Study Objectives:
Three of the most commonly used agents for conscious sedation in the Emergency Department (ED) are ketamine, fentanyl/versed, and propofol. In this study, we measured and compared the total times spent in the ED with each of these agents. Our objective was to determine whether the use of propofol for conscious sedation was associated with a shorter length of ED stay as compared to the other two agents.
This was a consecutive case series. All patients who required procedural conscious sedation who presented to the ED at University of California, Irvine Medical Center from January 2003 through April 2004 were included in the study. The attending ED physician evaluated the patient and determined which medication(s) would be administered. All patients underwent procedural sedation according to the ED’s standardized sedation protocol. The times and dosages of administered medications and the sedation/consciousness level (SCL) scores were recorded by ED nurses at 3–5 minute intervals. Data was abstracted prospectively. The time to sedation (first dose of agent to SCL score of 2 or less) and time to recovery (last dose of agent to SCL score of 4) of the different regimens were then analyzed and compared.
Thirty-eight patients received propofol, 38 received ketamine, and 14 received fentanyl/versed. The mean times to sedation (minutes) were: propofol 4.5 (95% CI: 3.3–5.7), ketamine 10.6 (95% CI: 5.8–15.4), fentanyl/versed 11.5 (95% CI: 3.5–19.4). The mean times to recovery were: propofol 21.6 (95% CI: 16.1–27.1), ketamine 55.4 (95% CI: 46.2–64.5), fentanyl/versed 59.9 (95% CI: 20.3–99.5). Propofol had a statistically significant shorter time to sedation than both ketamine (p<.001) and fentanyl/versed (p=.022). Propofol also produced shorter recovery times than both ketamine (p<.001) and fentanyl/versed (p=.002).
In this study, sedation and recovery times were shorter with propofol than with ketamine or fentanyl/versed. The use of propofol for conscious sedation in this non-randomized study was associated with a shorter ED length of stay.
PMCID: PMC2872520  PMID: 20505814

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