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1.  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
2.  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
3.  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
4.  Effect of an analgo-sedation protocol for neurointensive patients: a two-phase interventional non-randomized pilot study 
Critical Care  2010;14(2):R71.
Sedation protocols are needed for neurointensive patients. The aim of this pilot study was to describe sedation practice at a neurointensive care unit and to assess the feasibility and efficacy of a new sedation protocol. The primary outcomes were a shift from sedation-based to analgesia-based sedation and improved pain management. The secondary outcomes were a reduction in unplanned extubations and duration of sedation.
This was a two-phase (before-after), prospective controlled study at a university-affiliated, 14-bed neurointensive care unit in Denmark. The sample included patients requiring mechanical ventilation for at least 48 hours treated with continuous sedative and analgesic infusions or both. During the observation phase the participants (n = 106) were sedated as usual (non-protocolized), and during the intervention phase the participants (n = 109) were managed according to a new sedation protocol.
Our study showed a shift toward analgo-sedation, suggesting feasibility of the protocol. We found a significant reduction in the use of propofol (P < .001) and midazolam (P = .001) and an increase in fentanyl (P < .001) and remifentanil (P = .003). Patients selected for daily sedation interruption woke up faster, and estimates of pain free patients increased from 56.8% to 82.7% (P < .001), suggesting efficacy of the protocol. The duration of sedation and unplanned extubations were unchanged.
Our pilot study showed feasibility and partial efficacy of our protocol. Some neurointensive patients might not benefit from protocolized practice. We recommend an interdisciplinary effort to target patients requiring less sedation, as issues of oversedation and inadequate pain management still need more attention.
Trial registration
PMCID: PMC2887194  PMID: 20403186
5.  Cocktail sedation containing propofol versus conventional sedation for ERCP: a prospective, randomized controlled study 
BMC Anesthesiology  2012;12:20.
ERCP practically requires moderate to deep sedation controlled by a combination of benzodiazepine and opiod. Propofol as a sole agent may cause oversedation. A combination (cocktail) of infused propofol, meperidine, and midazolam can reduce the dosage of propofol and we hypothesized that it might decrease the risk of oversedation. We prospectively compare the efficacy, recovery time, patient satisfactory, and side effects between cocktail and conventional sedations in patients undergoing ERCP.
ERCP patients were randomized into 2 groups; the cocktail group (n = 103) and the controls (n = 102). For induction, a combination of 25 mg of meperidine and 2.5 mg of midazolam were administered in both groups. In the cocktail group, a bolus dose of propofol 1 mg/kg was administered and continuously infused. In the controls, 25 mg of meperidine or 2.5 mg/kg of midazolam were titrated to maintain the level of sedation.
In the cocktail group, the average administration rate of propofol was 6.2 mg/kg/hr. In the control group; average weight base dosage of meperidine and midazolam were 1.03 mg/kg and 0.12 mg/kg, respectively. Recovery times and patients’ satisfaction scores in the cocktail and control groups were 9.67 minutes and 12.89 minutes (P = 0.045), 93.1and 87.6 (P <0.001), respectively. Desaturation rates in the cocktail and conventional groups were 58.3% and 31.4% (P <0.001), respectively. All desaturations were corrected with temporary oxygen supplementation without the need for scope removal.
Cocktail sedation containing propofol provides faster recovery time and better patients’ satisfaction for patients undergoing ERCP. However, mild degree of desaturation may still develop.
Trial registration, NCT01540084
PMCID: PMC3434082  PMID: 22873637
Cocktail sedation containing propofol; Meperidine; Midazolam; ERCP
6.  Carbon dioxide accumulation during analgosedated colonoscopy: Comparison of propofol and midazolam 
AIM: To characterize the profiles of alveolar hypoventilation during colonoscopies performed under sedoanalgesia with a combination of alfentanil and either midazolam or propofol.
METHODS: Consecutive patients undergoing routine colonoscopy were randomly assigned to sedation with either propofol or midazolam in an open-labeled design using a titration scheme. All patients received 4 μg/kg per body weight alfentanil for analgesia and 3 L of supplemental oxygen. Oxygen saturation (SpO2) was measured by pulse oximetry (POX), and capnography (PcCO2) was continuously measured using a combined dedicated sensor at the ear lobe. Instances of apnea resulting in measures such as stimulation of the patient, a chin lift, a mask maneuver, or withholding of sedation were recorded. PcCO2 values (as a parameter of sedation-induced hypoventilation) were compared between groups at the following distinct time points: baseline, maximal rise, termination of the procedure and 5 min after termination of the procedure. The number of patients in both study groups who regained baseline PcCO2 values (± 1.5 mmHg) five minutes after the procedure was determined.
RESULTS: A total of 97 patients entered this study. The data from 14 patients were subsequently excluded for clinical procedure-related reasons or for technical problems. Therefore, 83 patients (mean age 62 ± 13 years) were successfully randomized to receive propofol (n = 42) or midazolam (n = 41) for sedation. Most of the patients were classified as American Society of Anesthesiologists (ASA) II [16 (38%) in the midazolam group and 15 (32%) in the propofol group] and ASA III [14 (33%) and 13 (32%) in the midazolam and propofol groups, respectively]. A mean dose of 5 (4-7) mg of IV midazolam and 131 (70-260) mg of IV propofol was used during the procedure in the corresponding study arms. The mean SpO2 at baseline (%) was 99 ± 1 for the midazolam group and 99 ± 1 for the propofol group. No cases of hypoxemia (SpO2 < 85%) or apnea were recorded. However, an increase in PcCO2 that indicated alveolar hypoventilation occurred in both groups after administration of the first drug and was not detected with pulse oximetry alone. The mean interval between the initiation of sedation and the time when the PcCO2 value increased to more than 2 mmHg was 2.8 ± 1.3 min for midazolam and 2.8 ± 1.1 min for propofol. The mean maximal rise was similar for both drugs: 8.6 ± 3.7 mmHg for midazolam and 7.4 ± 3.2 mmHg for propofol. Five minutes after the end of the procedure, the mean difference from the baseline values was significantly lower for the propofol treatment compared with midazolam (0.9 ± 3.0 mmHg vs 4.3 ± 3.7 mmHg, P = 0.0000169), and significantly more patients in the propofol group had regained their baseline value ± 1.5 mmHg (32 of 41 vs 12 of 42, P = 0.0004).
CONCLUSION: A significantly higher number of patients sedated with propofol had normalized PcCO2 values five minutes after sedation when compared with patients sedated with midazolam.
PMCID: PMC3471107  PMID: 23082055
Colonoscopy; Deep sedation; Propofol; Hypoventilation; Blood gas monitoring; Transcutaneous
7.  Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care 
Critical Care  2000;4(5):302-308.
The respiratory effects of dexmedetomidine were retrospectively examined in 33 postsurgical patients involved in a randomised, placebo-controlled trial after extubation in the intensive care unit (ICU). Morphine requirements were reduced by over 50% in patients receiving dexmedetomidine. There were no differences in respiratory rates, oxygen saturations, arterial pH and arterial partial carbon dioxide tension (PaCO2) between the groups. Interestingly the arterial partial oxygen tension (PaO2) : fractional inspired oxygen (FIO2) ratios were statistically significantly higher in the dexmedetomidine group. Dexmedetomidine provides important postsurgical analgesia and appears to have no clinically important adverse effects on respiration in the surgical patient who requires intensive care.
The α2-agonist dexmedetomidine is a new class of sedative drug that is being investigated for use in ICU settings. It is an effective agent for the management of sedation and analgesia after cardiac, general, orthopaedic, head and neck, oncological and vascular surgery in the ICU [1]. Cardiovascular stability was demonstrated, with significant reductions in rate-pressure product during sedation and over the extubation period.
Dexmedetomidine possesses several properties that may additionally benefit those critically ill patients who require sedation. In spontaneously breathing volunteers, intravenous dexmedetomidine caused marked sedation with only mild reductions in resting ventilation at higher doses [2]. Dexmedetomidine reduces the haemodynamic response to intubation and extubation [3,4,5] and attenuates the stress response to surgery [6], as a result of the α2-mediated reduction in sympathetic tone. Therefore, it should be possible to continue sedation with dexmedetomidine over the stressful extubation period without concerns over respiratory depression, while ensuring that haemodynamic stability is preserved.
The present study is a retrospective analysis of the respiratory response to dexmedetomidine in 33 postsurgical patients (who were involved in a randomized, double-blind, placebo-controlled trial [1]) after extubation in the ICU.
Patients who participated in the present study were admitted after surgery to our general or cardiothoracic ICUs, and were expected to receive at least 6 h of postsurgical sedation and artificial ventilation.
On arrival in the ICU after surgery, patients were randomized to receive either dexmedetomidine or placebo (normal saline) with rescue sedation and analgesia being provided, only if clinically needed, with midazolam and morphine boluses, respectively. Sedation was titrated to maintain a Ramsay Sedation Score [7] of 3 or greater while the patients were intubated, and infusions of study drug were continued for a maximum of 6 h after extubation to achieve a Ramsay Sedation Score of 2 or greater.
The patients were intubated and ventilated with oxygen-enriched air to attain acceptable arterial blood gases, and extubation occurred when clinically indicated. All patients received supplemental oxygen after extubation, which was delivered by a fixed performance device. Assessment of pain was by direct communication with the patient.
Results are expressed as mean ± standard deviation unless otherwise stated. Patient characteristics, operative details and morphine usage were analyzed using the Mann-Whitney U-test. Statistical differences for respiratory measurements between the two groups were determined using analysis of variance for repeated measures, with the Bonferroni test for post hoc comparisons.
Of the 40 patients who participated in the study, seven patients could not be included in the analysis of respiratory function because they did not receive a study drug infusion after extubation. Consequently, data from 33 patients are used in the analysis of respiratory function; 16 received dexmedetomidine and 17 placebo. Inadequate arterial blood gas analysis was available in five patients (two from the dexmedetomidine group, and three from the placebo group). There were no significant differences in patient characteristics and operative details between the groups.
Requirements for morphine were reduced by more than 50% in patients receiving dexmedetomidine when compared with placebo after extubation (0.003 ± 0.004 vs 0.008 ± 0.006 mg/kg per h; P= 0.040).
There were no statistically significant differences between placebo and dexmedetomidine for oxygen saturations measured by pulse oximetry (P= 0.26), respiratory rate (P= 0.16; Fig. 1), arterial pH (P= 0.77) and PaCO2 (P= 0.75; Fig. 2) for the 6 h after extubation.
The dexmedetomidine group showed significantly higher PaO2: FIO2 ratios throughout the 6-h intubation (P= 0.036) and extubation (P= 0.037) periods (Fig. 3). There were no adverse respiratory events seen in either the dexmedetomidine or placebo group.
Respiratory rate for the 6-h periods before and after extubation. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.
PaCO2 (PCO2) for the 6-h periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.
PaO2 : FIO2 ratio for the 6-h periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.
Lack of respiratory depression in patients sedated with α2-adrenoceptor agonists was first reported by Maxwell [8] in a study investigating the respiratory effects of clonidine. However, more recent data suggests that clonidine may cause mild respiratory depression in humans [9], and α2-adrenoceptor agonists are well known to produce profound intraoperative hypoxaemia in sheep [10,11]. The effects of dexmedetomidine on other ventilation parameters also appear to be species specific [12].
Belleville et al [2] investigated the ventilatory effects of a 2-min intravenous infusion of dexmedetomidine on human volunteers. According to those investigators, minute ventilation and arterial PaCO2 were mildly decreased and increased, respectively. There was a rightward shift and depression of the hypercapnic response with infusions of 1.0 and 2.0 μg/kg.
Previous studies that investigated the respiratory effects of dexmedetomidine have only been performed in healthy human volunteers, who have received either single intramuscular injections or short (= 10 min) intravenous infusions of dexmedetomidine. It is therefore reassuring that no deleterious clinical effects on respiration and gas exchange were seen in the patients we studied, who were receiving long-term infusions. However, there are important limitations to the present results. No dose/response curve for dexmedetomidine can be formulated from the data, and further investigation is probably ethically difficult to achieve in the spontaneously ventilating intensive care patient. We also have no data on the ventilatory responses to hypercapnia and hypoxia, which would also be difficult to examine practically and ethically. The placebo group received more than twice as much morphine as patients receiving dexmedetomidine infusions after extubation, but there were no differences in respiratory rate or PaCO2 between the groups. We can not therefore determine from this study whether dexmedetomidine has any benefits over morphine from a respiratory perspective.
There were no differences in oxygen saturations between the groups because the administered oxygen concentration was adjusted to maintain satisfactory gas exchange. Interestingly, however, there were statistically significant higher PaO2 : FIO2 ratios in the dexmedetomidine group. This ratio allows for the variation in administered oxygen to patients during the study period, and gives some clinical indication of alveolar gas exchange. However, this variable was not a primary outcome variable for the present study, and may represent a type 1 error, although post hoc analysis reveals that the data have 80% power to detect a significant difference (α value 0.05). Further studies are obviously required.
Sedation continued over the extubation period, has been shown to reduce haemodynamic disturbances and myocardial ischaemia [13]. We have previously shown [1] that dexmedetomidine provides cardiovascular stability, with a reduction in rate-pressure product over the extubation period. A sedative agent that has analgesic properties, minimal effects on respiration and offers ischaemia protection would have enormous potential in the ICU. Dexmedetomidine may fulfill all of these roles, but at present we can only conclude that dexmedetomidine has no deleterious clinical effects on respiration when used in doses that are sufficient to provide adequate sedation and effective analgesia in the surgical population requiring intensive care.
PMCID: PMC29047  PMID: 11056756
α2-Adrenoceptor agonist; analgesia; dexmedetomidine; intensive care; postoperative; respiratory; sedation
8.  Sedation Depth During Spinal Anesthesia and the Development of Postoperative Delirium in Elderly Patients Undergoing Hip Fracture Repair 
Mayo Clinic Proceedings  2010;85(1):18-26.
OBJECTIVE: To determine whether limiting intraoperative sedation depth during spinal anesthesia for hip fracture repair in elderly patients can decrease the prevalence of postoperative delirium.
PATIENTS AND METHODS: We performed a double-blind, randomized controlled trial at an academic medical center of elderly patients (≥65 years) without preoperative delirium or severe dementia who underwent hip fracture repair under spinal anesthesia with propofol sedation. Sedation depth was titrated using processed electroencephalography with the bispectral index (BIS), and patients were randomized to receive either deep (BIS, approximately 50) or light (BIS, ≥80) sedation. Postoperative delirium was assessed as defined by Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) criteria using the Confusion Assessment Method beginning at any time from the second day after surgery.
RESULTS: From April 2, 2005, through October 30, 2008, a total of 114 patients were randomized. The prevalence of postoperative delirium was significantly lower in the light sedation group (11/57 [19%] vs 23/57 [40%] in the deep sedation group; P=.02), indicating that 1 incident of delirium will be prevented for every 4.7 patients treated with light sedation. The mean ± SD number of days of delirium during hospitalization was lower in the light sedation group than in the deep sedation group (0.5±1.5 days vs 1.4±4.0 days; P=.01).
CONCLUSION: The use of light propofol sedation decreased the prevalence of postoperative delirium by 50% compared with deep sedation. Limiting depth of sedation during spinal anesthesia is a simple, safe, and cost-effective intervention for preventing postoperative delirium in elderly patients that could be widely and readily adopted.
Trial Registration: Identifier: NCT00590707
Use of light propofol sedation decreased the prevalence of postoperative delirium by 50% compared with deep sedation. Limiting depth of sedation during spinal anesthesia is a simple, safe, and cost-effective intervention for preventing postoperative delirium in elderly patients that could be widely and readily adopted.
PMCID: PMC2800291  PMID: 20042557
9.  An Evaluation of Intranasal Sufentanil and Dexmedetomidine for Pediatric Dental Sedation 
Pharmaceutics  2014;6(1):175-184.
Conscious or moderate sedation is routinely used to facilitate the dental care of the pre- or un-cooperative child. Dexmedetomidine (DEX) has little respiratory depressant effect, possibly making it a safer option when used as an adjunct to either opioids or benzodiazepines. Unlike intranasal (IN) midazolam, IN application of DEX and sufentanil (SUF) does not appear to cause much discomfort. Further, although DEX lacks respiratory depressive effects, it is an α2-agonist that can cause hypotension and bradycardia when given in high doses or during prolonged periods of administration. The aim of this feasibility study was to prospectively assess IN DEX/SUF as a potential sedation regimen for pediatric dental procedures. After IRB approval and informed consent, children (aged 3–7 years; n = 20) from our dental clinic were recruited. All patients received 2 μg/kg (max 40 μg) of IN DEX 45 min before the procedure, followed 30 min later by 1 μg/kg (max 20 μg) of IN SUF. An independent observer rated the effects of sedation using the Ohio State University Behavior Rating Scale (OSUBRS) and University of Michigan Sedation Scale (UMSS). The dentist and the parent also assessed the efficacy of sedation. Dental procedures were well tolerated and none were aborted. The mean OSUBRS procedure score was 2.1, the UMSS procedure score was 1.6, and all scores returned to baseline after the procedure. The average dentist rated quality of sedation was 7.6 across the 20 subjects. After discharge, parents reported one child with prolonged drowsiness and one child who vomited at home. The use of IN DEX supplemented with IN SUF provided both an effective and tolerable form of moderate sedation. Although onset and recovery are slower than with oral (PO) midazolam and transmucosal fentanyl, the quality of the sedation may be better with less risk of respiratory depression. Results from this preliminary study showed no major complications from IN delivery of these agents.
PMCID: PMC3978530  PMID: 24662315
pediatric sedation; pediatric dentistry; intranasal drug administration
10.  Dexmedetomidine ameliorates monitored anaesthesia care 
Indian Journal of Anaesthesia  2014;58(2):154-159.
Background and Aims:
Monitored anaesthesia care (MAC) is meant for procedures under local anaesthesia. Various drugs have been used for this purpose. The recently introduced alpha2 agonist, dexmedetomidine provides “conscious sedation” with adequate analgesia and minimal respiratory depression. Hence, the safety and efficacy of two doses of dexmedetomidine for sedation and analgesia were evaluated.
A total of 90 patients were distributed in three groups of 30 each: Dexmedetomidine 0.5 μg/kg (DL), dexmedetomidine 1.0 μg/kg (DH) and normal saline (C). The initial loading dose was followed by maintenance infusion of 0.2-0.7 μg/kg/h of dexmedetomidine or equivalent volume of saline. Study drug was started at least 15 min before placement of local anaesthesia. Drugs were titrated to a target level of sedation (=3 on Ramsay sedation scale [RSS]). Midazolam 0.02 mg/kg for RSS < 3 and fentanyl 0.5 μg/kg were supplemented as required. The statistical analysis was performed using Chi-square test and mean and anova analysis.
In groups DL and DH fewer patients required supplemental midazolam, 56.7% (17/30) and 40% (12/30), compared with control, where 86.7% (26/30)needed midazolam supplements. P = 0.000. Both groups DL and DH required significantly less fentanyl (84.8 and 83.9 μg) versus control (144.2 μg). There was significantly increased ease of achieving and maintaining targeted sedation and analgesia in both dexmedetomidine groups when compared with placebo (P = 0.001). Adverse events observed with dexmedetomidine were bradycardia and hypotension.
Dexmedetomidine in the doses studied was considered safe and effective sedative and analgesic for patients undergoing procedures under MAC.
PMCID: PMC4050931  PMID: 24963179
Conscious sedation; dexmedetomidine; monitored anaesthesia care; respiratory depression
11.  Comparison of dexmedetomidine and midazolam for monitored anesthesia care combined with tramadol via patient-controlled analgesia in endoscopic nasal surgery: A prospective, randomized, double-blind, clinical study 
Monitored anesthesia care (MAC) may be applied for septoplasty or endoscopic sinus surgery in which an adequate sedation and analgesia without respiratory depression are desired for comfort of both the patient and the surgeon. Several combinations with different agents have been used for this purpose in these patients. However, analgesic properties for these agents have not been reported.
The aim of this study was to investigate the analgesic and sedative effects of dexmedetomidine or midazolam infusion combined with tramadol that was used via patient-controlled analgesia (PCA), and to document the effects of these drugs on early cognitive functions.
This prospective, randomized, double-blind, clinical study enrolled patients undergoing septoplasty or endoscopic sinus surgery at the Abant Izzet Baysal University Hospital, Bolu, Turkey, between February and September 2006. Patients were randomly allocated in a 1:1 ratio into 1 of 2 groups: the dexmedetomidine group (group D) patients received IV dexmedetomidine 1 μg/kg for 10 minutes followed by continuous infusion of 0.5 μg/kg · h−1; and the midazolam group (group M) patients were administered a loading dose of IV midazolam 40 μg/kg for 10 minutes followed by infusion at the rate of 50 μg/kg · h−1. A 1-minute bolus dose of IV tramadol (1.5 mg/kg) was administered in both groups 10 minutes after the administration of the primary drug, and continued via infusion using a PCA device. After baseline measurements, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), oxygen saturation, and rate of respiration were recorded after the loading dose of study drug, after the bolus tramadol dose, at 10-minute intervals during the operation, and twice in the recovery rooms; 5 minutes after arrival and 5 minutes before discharge. Verbal rating score (VRS) and Ramsay sedation score were determined at baseline (after surgery was started), every 10 minutes thereafter until the end of the operation, and 2 times during recovery. All patients were assessed with the Wechsler Memory Scale-Revised at baseline (preoperatively) and 4 hours after the operation.
Seventy patients were enrolled in the study and randomly assigned to 1 of 2 groups: group D (sex, male/female, 23/12; mean [SEM] age, 32.53 [2.07] years; mean [SEM] weight, 73.03 [2.41] kg) or group M (sex, male/female, 21/14; mean [SEM] age, 34.43 [1.83] years; mean [SEM] weight, 67.90 [2.32] kg). All hemodynamic parameters (SAP, DAP, MAP, HR) were significantly higher in group M compared with group D from the onset of the surgery to discharge time (P < 0.05). Pain and sedation scores were similar in both groups, but the amount of PCA-administered rescue tramadol was significantly higher in group M (P = 0.001). A higher, though not statistically significant, prevalence of adverse events (ie, hypotension, bradycardia, and perioperative nausea and vomiting) were observed in group D. Postoperative logical verbal memory and digit span values were significantly higher in group D when compared with group M (P < 0.05). Postoperative digit span and visual reproduction scores were significantly higher than preoperative values in group D (P < 0.05). Postoperative personality functioning scores were significantly higher than preoperative values in group M (P < 0.05).
Based on VRS, Ramsay sedation scores, and surgeon and anesthesiologist satisfaction scores, dexmedetomidine or midazolam combined with tramadol PCA provided adequate analgesia and sedation in these adult patients undergoing septoplasty or endoscopic sinus surgery with MAC. A significantly larger amount of rescue tramadol was used by group M, suggesting that a better analgesic effect was achieved with dexmedetomidine.
PMCID: PMC3965987  PMID: 24678121
dexmedetomidine; midazolam; sedoanalgesia; cognitive function
12.  Patient-controlled sedation with propofol/remifentanil versus propofol/alfentanil for patients undergoing outpatient colonoscopy, a randomized, controlled double-blind study 
Saudi Journal of Anaesthesia  2014;8(Suppl 1):S36-S40.
Many techniques are used for sedation of colonoscopies. Patient-controlled sedation (PCS) is utilizing many drugs or drug combinations.
The aim of this study is to compare the safety and feasibility of propofol/remifentanil versus propofol/alfentanil given to sedate patients undergoing outpatient colonoscopies through a patient-controlled technique.
Settings and Design:
Controlled randomized and double-blind study.
Materials and Methods:
A total of 80 patients were randomly divided into two groups; PA group received a combination of propofol/alfentanil and PR group received propofol/remifentanil combination. Patients were monitored for heart rate (HR), blood pressure (BP), oxygen saturation, and Ramsay sedation scale (RSS). Times of the following events were recorded; initiation of sedation, insertion and removal of the colonoscope, recovery and discharge. Five intervals were calculated; time to sedation, procedure time, postprocedure time, procedure room time, and postanesthesia care unit (PACU) time. Endoscopist and patient satisfaction scores were obtained.
Statistical Analysis Used:
Unpaired Student's t-test was used to compare between the two groups. Paired Student's t-test was used to compare baseline readings with readings after 30 min of sedation in the same group when needed.
Both groups showed slowing of the HR and decrease in mean arterial BP. HR and mean arterial BP were significantly lower 5 and 10 min after initiation of sedation in PR group when compared with PA group. Both HR and mean arterial BP returned to presedation readings 30 min after initiation of sedation in PR group but not in PA group. No differences between the two groups concerning oxygen saturation, RSS, endoscopist and patient satisfaction scores. Postprocedure and PACU times were significantly prolonged in PA group.
PCS with either remifentanil/propofol or alfentanil/propofol for patients undergoing outpatient colonoscopy is safe and feasible. Remifentanil/proofol has more beneficial advantages in this setting secondary to its more rapid clearance.
PMCID: PMC4268525  PMID: 25538518
Alfentanil; colonoscopy; patient-controlled sedation; remifentanil
13.  A prospective study of high dose sedation for rapid tranquilisation of acute behavioural disturbance in an acute mental health unit 
BMC Psychiatry  2013;13:225.
Acute behavioural disturbance (ABD) is a common problem in psychiatry and both physical restraint and involuntary parenteral sedation are often required to control patients. Although guidelines are available, clinical practice is often guided by experience and there is little agreement on which drugs should be first-line treatment for rapid tranquilisation. This study aimed to investigate sedation for ABD in an acute mental healthcare unit, including the effectiveness and safety of high dose sedation.
A prospective study of parenteral sedation for ABD in mental health patients was conducted from July 2010 to June 2011. Drug administration (type, dose, additional doses), time to sedation, vital signs and adverse effects were recorded. High dose parenteral sedation was defined as greater than the equivalent of 10 mg midazolam, droperidol or haloperidol (alone or in combination), compared to patients receiving 10 mg or less (normal dose). Effective sedation was defined as a fall in the sedation assessment tool score by two or a score of zero or less. Outcomes included frequency of adverse drug effects, time to sedation/tranquilisation and use of additional sedation.
Parenteral sedation was given in 171 cases. A single drug was given in 96 (56%), including droperidol (74), midazolam (19) and haloperidol (3). Effective sedation occurred in 157 patients (92%), and the median time to sedation was 20 min (Range: 5 to 100 min). The median time to sedation for 93 patients receiving high dose sedation was 20 min (5-90 min) compared to 20 min (5-100 min; p = 0.92) for 78 patients receiving normal dose sedation. Adverse effects occurred in 16 patients (9%); hypotension (14), oxygen desaturation (1), hypotension and oxygen desaturation (1). There were more adverse effects in the high dose sedation group compared to the normal dose group [11/93 (12%) vs. 5/78 (6%); p = 0.3]. Additional sedation was given in 9 of 171 patients (5%), seven in the high dose and two in the normal dose groups.
Large initial doses of sedative drugs were used for ABD in just over half of cases and additional sedation was uncommon. High dose sedation did not result in more rapid or effective sedation but was associated with more adverse effects.
PMCID: PMC3848824  PMID: 24044673
Violence; Sedation; Acute psychiatric unit; Droperidol; Benzodiazepine; Antipsychotic
14.  A prospective randomized double-blind study comparing dexmedetomidine vs. combination of midazolam-fentanyl for tympanoplasty surgery under monitored anesthesia care 
Analgesia and sedation are usually required for the comfort of the patient and surgeon during tympanoplasty surgery done under local anesthesia. In this study, satisfaction scores and effectiveness of sedation and analgesia with dexmedetomidine were compared with a combination of midazolam-fentanyl.
Materials and Methods:
Ninety patients undergoing tympanoplasty under local anesthesia randomly received either IV dexmedetomidine 1 μg kg-1 over 10 min followed by 0.2 μg kg-1h-1 infusion (Group D) or IV midazolam 0.06 mg kg-1 plus IV fentanyl 1 μg kg-1 over 10 min (Group MF) followed by normal saline infusion at 0.2 ml kg-1h-1. Sedation was titrated to Ramsay sedation score (RSS) of three. Vital parameters, rescue analgesics (fentanyl 1 μg kg-1) and sedatives (midazolam 0.01 mg kg-1), patient and surgeon satisfaction scores were recorded.
Patient and surgeon satisfaction score was better in Group D than Group MF (median interquartile range (IQR) 9 (8-10) vs. 8 (6.5-9.5) and 9 (8.5-9.5) vs. 8 (6.75-9.25), P = 0.0001 for both). Intraoperative heart rate and mean arterial pressure in Group D were lower than the baseline values and the corresponding values in Group MF (P < 0.05). Percentage of patients requiring rescue fentanyl was higher in Group MF than Group D (40% vs. 11.1%, P = 0.01). One patient in Group D while four in Group MF (8.8%) required rescue sedation with midazolam (P > 0.17). Seven patients in Group D had dry mouth vs. none in Group MF (P = 0.006). One patient in Group D had bradycardia with hypotension which was effectively treated.
Dexmedetomidine is comparable to midazolam-fentanyl for sedation and analgesia in tympanoplasty with better surgeon and patient satisfaction. Hemodynamics need to be closely monitored.
PMCID: PMC3713662  PMID: 23878436
Dexmedetomidine; sedation; midazolam fentanyl sedation; monitored anesthesia care; satisfaction scores; surgery; otological
15.  Assessment of the effects of ketamine-fentanyl combination versus propofol-remifentanil combination for sedation during endoscopic retrograde cholangiopancreatography 
Endoscopic retrograde cholangiopancreatography (ERCP) as a diagnostic and treatment procedure is used in most biliary tract and pancreatic. Either sedation or general anesthesia could be considered for this procedure. Combining a sedative with an opioid agent can provide effective moderate sedation. This study compared the impact of ketamine-fentanyl (KF) versus propofol-remifentanil (PR) on sedation scale in patients undergoing ERCP.
Materials and Methods:
As a double-blinded randomized clinical trial, 80 patients selected by convenient sampling, allocated randomly into two groups. KF group received ketamine 0.5 mg/kg body weight intravenously over 60 s and then fentanyl 1 mcg/kg body weight intravenously. PR group received propofol l mg/kg body weight intravenously over 60 s and then remifentanil 0.05 mcg/kg body weight/min intravenously. Intravenous (IV) infusion of propofol was maintained by 50 mcg/kg body weight/min throughout ERCP. Ramsay Sedation Score, vital signs, oxygen saturation (SpO2), recovery score (modified Aldrete score) and visual analog scales of pain intensity, and endoscopist's satisfaction were considered as measured outcomes. All analysis were analyzed by SPSS Statistics version 22 and using t-test, Chi-square and repeated measured ANOVA and Mann-Whitney tests for data analysis.
Respiratory rate and SpO2 level during the time intervals were lower in PR group (P < 0.001). Sedation score at intervals was not significantly different (P = 0.07). The frequency of apnea in PR group was significantly higher than the KF group (P = 0.003). The percentage of need to supplemental oxygen in PR group was 35.1% that was also significantly higher than 8.8% in the KF group (P = 0.008), but the dosage frequency was significantly higher in KF group (P < 0.001). The KF and PR groups average length of stay in the recovery room were 50.71 standard deviation (SD = 9.99) and 42.57 (SD = 11.99) minutes, respectively, indicating a significant difference (P = 0.003). The mean severity of nausea in KF and PR groups was, respectively, 2.74 confidence interval (CI = 1.68-3.81) and 0.43 (CI = 0.11-0.75), that was significantly higher in KF group (P < 0.001). The average score of surgeon satisfaction in both KF and PR groups were 7.69 (CI = 7.16-8.21) and 8.65 (CI = 8.25-9.05), respectively, which was higher in KF group (P = 0.004), but the average level of patients satisfaction in KF group was 8.86 (CI = 8.53-9.19) and in PR group was 8.95 (CI - 8.54-9.35) that were not significantly different (P = 0.074).
There is no statistically significant difference between KF and PR combinations in sedation score, but PR combination provides better pain control, with less nausea and shorter recovery time while causing more respiratory side effects, that is, apnea and need to oxygen.
PMCID: PMC4268195  PMID: 25535501
Endoscopic retrograde cholangiopancreatography; fentanyl; ketamine; propofol; remifentanil
16.  Dexmedetomidine is effective for monitored anesthesia care in outpatients undergoing cataract surgery 
Korean Journal of Anesthesiology  2011;61(6):453-459.
Dexmedetomidine has a sedative analgesic property without respiratory depression. This study evaluated the efficacy of dexmedetomidine as an appropriate sedative drug for monitored anesthesia care (MAC) in outpatients undergoing cataract surgery on both eyes compared with combination of propofol and alfentanil.
Thirty-one eligible patients were randomly divided into two groups on the first operation day. Dexmedetomidine was administered in group D at 0.6 µg/kg/h, and propofol and alfentanil was infused concomitantly in group P at a rate of 2 mg/kg/h and 20 µg/kg/h, respectively. Sedation was titrated at Ramsay sedation score 3. Iowa satisfaction with anesthesia scale (ISAS) of the patients was evaluated postoperatively. Systolic blood pressure (SBP), heart rate (HR), respiration rate (RR), and peripheral oxygen saturation (SpO2) were recorded throughout the surgery. For the second operation, the group assignments were exchanged.
Postoperative ISAS was 50.3 (6.2) in group D and 42.7 (8.7) in group P, which was statistically significant (P < 0.001). SBP was significantly lower in group D compared with group P from the beginning of the operation. HR, RR, and SpO2 were comparable between the two groups. There were 8 cases (25.8%) of hypertension in group P, and 1 case (3.2%) in group D (P < 0.05). In contrast, 1 case (3.2%) of hypotension and 1 case (3.2%) of bradycardia occurred in group D.
Compared with the combined use of propofol and alfentanil, dexmedetomidine could be used appropriately for MAC in cataract surgery with better satisfaction from the patients and a more stable cardiovascular state.
PMCID: PMC3249565  PMID: 22220220
Cataract; Dexmedetomidine; Monitored anesthesia care; Propofol
17.  Comparative evaluation of recovery characteristics of fentanyl and butorphanol when used as supplement to propofol anaesthesia 
Background and Aim:
Narcotics have been used since long as a component of balanced anaesthesia, thus minimizing the anaesthetic requirement both during induction and maintenance as well as attenuating the pressor response during laryngoscopy and intubation. Equally significant is their role in provision of smoother recovery period by minimizing postoperative pain. Other than pain, the factors like postoperative nausea and vomiting (PONV), shivering, sedation and respiratory depression are equally important in recovery from the effects of anaesthetic drugs. The present study aimed at comparing the postoperative recovery characterstics of fentanyl and butorphanol in patients undergoing open cholecystectomy under general anaesthesia.
Materials and Methods:
The present study configured one hundred adults patients of American Society of Anaesthesiologists (ASA) grade 1 or 2 of either sex scheduled to undergo elective open cholecystectomy and were randomly assigned to receive fentanyl (group F; n = 50) or butorphanol (group B; n = 50). Both group were premedicated with midazolam 0.04 mg/kg intravenously followed by injection fentanyl 2 mcg/kg or butorphanol 40 mcg/kg. Standard induction was done with propofol 2 mg/kg and vecuronium 0.1 mg/kg was used for intubation. Anaesthesia was maintained with propofol infusion and 67% nitrous oxide in oxygen. Intraoperative hemodynamic parameters were observed and recorded. Postoperatively analgesia, sedation, PONV, shivering, respiratory depression and recovery score were observed.
The recovery time was less in group F (P > 0.05) while post operative analgesia (P < 0.001) and sedation (P > 0.05) was more in group B. The incidence of respiratory depression was more in group B (P > 0.05). PONV was comparable in both the groups. Postoperative shivering was significantly low in group B (P < 0.05).
It is concluded that besides easy availability and lower cost, butorphanol decreased propofol consumption intraoperatively and provided better analgesia and prophylaxis against shivering in postoperative period.
PMCID: PMC3678702  PMID: 23776820
Butorphanol; fentanyl; propofol; recovery
18.  Propofol versus Midazolam for Upper Gastrointestinal Endoscopy in Cirrhotic Patients: A Meta-Analysis of Randomized Controlled Trials 
PLoS ONE  2015;10(2):e0117585.
Sedation during gastrointestinal endoscopy is often achieved using propofol or midazolam in general population. However, impaired protein synthesis, altered drug metabolism, and compromised hepatic blood flow in patients with liver cirrhosis might affect the pharmacokinetics of sedatives, placing cirrhotic patients undergoing endoscopy at a greater risk of adverse events. The objective of this study was to assess comparative efficacies and safety of propofol and midazolam in cirrhotic patients undergoing endoscopy.
Randomized, controlled trials comparing propofol with midazolam in cirrhotic patients undergoing gastrointestinal endoscopy were selected. We performed the meta-analysis, using a random-effect model, the Review Manager, Version 5.2, statistical software package (Cochrane Collaboration, Oxford, UK) according to the PRISMA guidelines.
Five studies between 2003 and 2012, including 433 patients, were included. Propofol provided a shorter time to sedation (weight mean difference: -2.76 min, 95% confidence interval: -3.00 to -2.51) and a shorter recovery time (weight mean difference -6.17 min, 95% confidence interval: -6.81 to -5.54) than midazolam did. No intergroup difference in the incidence of hypotension, bradycardia, or hypoxemia was observed. Midazolam was associated with the deterioration of psychometric scores for a longer period than propofol.
This meta-analysis suggests that Propofol sedation for endoscopy provides more rapid sedation and recovery than midazolam does. The risk of sedation-related side effects for propofol does not differ significantly from that of midazolam. The efficacy of propofol in cirrhotic patients undergoing endoscopy is superior to those of midazolam.
PMCID: PMC4315567  PMID: 25646815
19.  Stepwise sedation for elderly patients with mild/moderate COPD during upper gastrointestinal endoscopy 
AIM: To investigate stepwise sedation for elderly patients with mild/moderate chronic obstructive pulmonary disease (COPD) during upper gastrointestinal (GI) endoscopy.
METHODS: Eighty-six elderly patients with mild/moderate COPD and 82 elderly patients without COPD scheduled for upper GI endoscopy were randomly assigned to receive one of the following two sedation methods: stepwise sedation involving three-stage administration of propofol combined with midazolam [COPD with stepwise sedation (group Cs), and non-COPD with stepwise sedation (group Ns)] or continuous sedation involving continuous administration of propofol combined with midazolam [COPD with continuous sedation (group Cc), and non-COPD with continuous sedation (group Nc)]. Saturation of peripheral oxygen (SpO2), blood pressure, and pulse rate were monitored, and patient discomfort, adverse events, drugs dosage, and recovery time were recorded.
RESULTS: All endoscopies were completed successfully. The occurrences of hypoxemia in groups Cs, Cc, Ns, and Nc were 4 (9.3%), 12 (27.9%), 3 (7.3%), and 5 (12.2%), respectively. The occurrence of hypoxemia in group Cs was significantly lower than that in group Cc (P < 0.05). The average decreases in value of SpO2, systolic blood pressure, and diastolic blood pressure in group Cs were significantly lower than those in group Cc. Additionally, propofol dosage and overall rate of adverse events in group Cs were lower than those in group Cc. Finally, the recovery time in group Cs was significantly shorter than that in group Cc, and that in group Ns was significantly shorter than that in group Nc (P < 0.001).
CONCLUSION: The stepwise sedation method is effective and safer than the continuous sedation method for elderly patients with mild/moderate COPD during upper GI endoscopy.
PMCID: PMC3732854  PMID: 23922479
Upper gastrointestinal endoscopy; Adverse events; Sedation; Monitoring; Chronic obstructive pulmonary disease
20.  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
21.  The impact of diphenhydramine and promethazine in patients undergoing advanced upper endoscopic procedures 
Endoscopic retrograde cholangiopancreatography (ERCP ) and endoscopic ultrasound (EUS) procedures are more complex and longer duration than standard endoscopy, requiring deeper levels of sedation. While prior studies have compared standard sedation (meperidine and midazolam) to propofol, no randomized, controlled trials have evaluated the use of adjunct sedatives in these procedures.
To prospectively compare the use of promethazine and diphenhydramine as adjunct sedatives to standard sedation in patients undergoing advanced endoscopic procedures.
This was a prospective, randomized, placebo-controlled study in a single, tertiary-care referral center. Promethazine (P), diphenhydramine (B), or normal saline (NS) were given as adjunct sedatives along with meperidine and midazolam in adult patients undergoing upper EUS and/or ERCP procedures. The main outcome measurement was sedation failure.
292 patients (P: 97, B: 93, NS: 102) were randomized over 36 months. No significant differences in sedation failures (P: 8, B: 13, NS: 11, p=0.449) or in the times needed to achieve adequate sedation (P: 11.8 minutes, B: 12.9 minutes, NS: 14.0 minutes, p=0.054) were seen between the groups. Sedation using P (43.7 minutes) was associated with a significantly longer recovery time compared to B (28.0 minutes) or NS (24.5 minutes).
The use of promethazine and diphenhydramine as adjunct sedatives did not improve sedation failure rates or reduce the time needed to achieve sedation in patients undergoing upper EUS or ERCP. Patients with anticipated sedation difficulties should proceed directly to propofol-based sedation.
PMCID: PMC3896573  PMID: 24498528
promethazine; diphenhydramine; endoscopic retrograde cholangiopancreatography; endoscopic ultrasound; sedation
22.  Dexmedetomidine as an adjunct to epidural analgesia after abdominal surgery in elderly intensive care patients: A prospective, double-blind, clinical trial 
Background: The ideal postoperative analgesia management of elderly surgical patients in intensive care units (ICUs) is continually being investigated.
Objective: The purpose of this study was to assess the effectiveness and tolerability of IV administration of dexmedetomidine as an adjunct to a low-dose epidural bupivacaine infusion for postoperative analgesia after abdominal surgery in elderly patients in the ICU.
Methods: ICU patients aged >70 years undergoing abdominal surgery were eligible for the study. A lumbar epidural catheter was inserted at the beginning of the surgery with no medication. On arrival at the ICU, the catheter was loaded with 0.25% bupivacaine 25 mg at the T8 to T10 sensory level, and a continuous infusion of 0.125% bupivacaine was started at 4 to 6 mL/h in combination with patient-controlled epidural analgesia (PCEA) of fentanyl (4 μg/bolus) for pain treatment. Patients in the treatment group received dexmedetomidine as an IV loading dose of 0.6 pg/kg for 30 minutes followed by continuous infusion at 0.2 μg/kg · h-1. Patients in the control group were not administered dexmedetomidine. The effectiveness of the pain relief was determined using a visual analog scale (VAS) (0 = no pain to 10 = worst pain imaginable) at rest. VAS score, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure, and arterial blood gases were monitored periodically for 24 hours after surgery. If required, tenoxicam (20-mg IV bolus) was used to ensure a VAS score of ≤3. The number of times PCEA and tenoxicam were administered and the occurrence of adverse events (AEs) were also recorded.
Results: Sixty patients (34 men, 26 women; mean [SD] age, 75.96 [4.25] years; mean [SD] weight, 74.13 [10.62] kg) were included in the study. VAS scores were significantly lower in the dexmedetomidine group compared with the control group at hours 1, 2, and 12 (VAS [hour 1]: 2.8 [0.4], P < 0.001; VAS [hour 2]: 2.7 [0.5], P < 0.001; and VAS [hour 12]: 0.9 [0.7], P 0.044). The mean number of administrations of fentanyl via PCEA was significantly greater in the control group compared with the dexmedetomidine group (2.20 vs 6.63 times; P < 0.001). The mean number of administrations of tenoxicam was significantly lower in the treatment group than the control group (0.27 vs 1.07 times; P < 0.001). In the control group, the decreases in sedation at 0, 8, 12, 16, and 20 hours were significant compared with baseline (P = 0.024, P = 0.001, P = 0.020, P < 0.001, and P = 0.005, respectively). Mean HR, SBR and AEs (eg, bradycardia [HR <60 beats/min], respiratory depression [respiratory rate <8 breaths/min], hypotension \SBP <90 mm Hg], oversedation, hypoxia, and hypercapnia) decreased significantly in the dexmedetomidine group (all, P < 0.05). Significantly more patients in the dexmedetomidine group rated their satisfaction with postoperative pain control as excellent compared with the control group (12 vs 6 patients; P = 0.014).
Conclusion: Intravenous dexmedetomidine was effective and generally well tolerated as an analgesic adjunct to epidural low-dose bupivacaine infusion for pain treatment, with lower need for opioids after abdominal surgery in these elderly intensive care patients than in the control group.
PMCID: PMC3969974  PMID: 24692779
postoperative analgesia; elderly patients; dexmedetomidine; epidural analgesia
23.  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
24.  Evaluation of a minimal sedation protocol using ICU sedative consumption as a monitoring tool: a quality improvement multicenter project 
Critical Care  2014;18(5):580.
Oversedation frequently occurs in ICUs. We aimed to evaluate a minimal sedation policy, using sedative consumption as a monitoring tool, in a network of ICUs targeting decrement of oversedation and mechanical ventilation (MV) duration.
A prospective quality improvement project was conducted in ten ICUs within a network of nonteaching hospitals in Brazil during a 2-year period (2010 to 2012). In the first 12 months (the preintervention period), we conducted an audit to identify sedation practice and barriers to current guideline-based practice regarding sedation. In the postintervention period, we implemented a multifaceted program, including multidisciplinary daily rounds, and monthly audits focusing on sedative consumption, feedback and benchmarking purposes. To analyze the effect of the campaign, we fit an interrupted time series (ITS). To account for variability among the network ICUs, we fit a hierarchical model.
During the study period, 21% of patients received MV (4,851/22,963). In the postintervention period, the length of MV was lower (3.91 ± 6.2 days versus 3.15 ± 4.6 days; mean difference, −0.76 (95% CI, −1.10; −0.43), P <0.001) and 28 ventilator-free days were higher (16.07 ± 12.2 days versus 18.33 ± 11.6 days; mean difference, 2.30 (95% CI, 1.57; 3.00), P <0.001) than in the preintervention period. Midazolam consumption (in milligrams per day of MV) decreased from 329 ± 70 mg/day to 163 ± 115 mg/day (mean difference, −167 (95% CI, −246; −87), P <0.001). In contrast, consumption of propofol (P = 0.007), dexmedetomidine (P = 0.017) and haloperidol (P = 0.002) increased in the postintervention period, without changes in the consumption of fentanyl. Through ITS, age (P = 0.574) and Simplified Acute Physiology Score III (P = 0.176) remained stable. The length of MV showed a secular effect (secular trend β1 = −0.055, P = 0.012) and a strong decrease immediately after the intervention (intervention β2 = −0.976, P <0.001). The impact was maintained over the course of one year, despite the waning trend for the intervention’s effect (postintervention trend β3 = 0.039, P = 0.095).
By using a light sedation policy in a group of nonteaching hospitals, we reproduced the benefits that have previously been demonstrated in controlled settings. Furthermore, systematic monitoring of sedative consumption should be a feasible instrument for supporting the implementation of a protocol on a large scale.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0580-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4234844
25.  Propofol-based deep sedation for endoscopic retrograde cholangiopancreatography procedure in sick elderly patients in a developing country 
The aim of this study was to evaluate and compare the clinical efficacy of propofol-based deep sedation (PBDS) for endoscopic retrograde cholangiopancreatography (ERCP) procedure in sick (American Society of Anesthesiologists [ASA] physical status III–IV) and nonsick (ASA physical status I–II) elderly patients in a teaching hospital in Thailand.
We undertook a retrospective review of the anesthesia or sedation service records of elderly patients who underwent ERCP procedures from October 2007 to September 2008. All patients were classified into two groups according to the ASA physical status. In group A, the patients had ASA physical status I–II, while in group B, the patients had ASA physical status III–IV. The primary outcome variable of the study was the successful completion of the procedure. The secondary outcome variables were sedation-related adverse events during and immediately after the procedure.
There were 158 elderly patients who underwent ERCP procedure by using PBDS during the study period. Of these, 109 patients were in group A and 49 patients were in group B. There were no significant differences in age, gender, weight, duration of ERCP, indication of procedure, and the mean dose of fentanyl, propofol, and midazolam between the two groups. All patients in both groups successfully completed the procedure except eight patients in group A and three patients in group B (P = 0.781). Overall, respiratory and cardiovascular adverse events in both groups were not significantly different. All adverse events were easily treated, with no adverse sequelae.
In the setting of a developing country, PBDS for ERCP procedure in sick elderly patients by trained anesthetic personnel with appropriate monitoring was safe and effective. The clinical efficacy of this technique in sick elderly patients was not different or worse than in nonsick elderly patients. Serious adverse events were rare in our population.
PMCID: PMC3132095  PMID: 21753887
deep sedation; endoscopic retrograde cholangiopancreatography; propofol (ERCP); sick; elderly; American Society of Anesthesiologists (ASA); developing country

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