Procedural sedation and analgesia is widely being used for female laparoscopic sterilization using combinations of different drugs at varying doses. This study compared the combination of fentanyl and propofol, and ketamine and propofol in patients undergoing outpatient laparoscopic tubal ligation, with respect to their hemodynamic effects, postoperative recovery characteristics, duration of hospital stay, adverse effects, and patient comfort and acceptability.
Settings and Design:
Randomized, double blind.
Patients were assigned to receive premixed injection of either fentanyl 1.5 μg/kg + propofol 2 mg/kg (Group PF, n=50) or ketamine 0.5 mg/kg + propofol 2 mg/kg (Group PK, n=50). Hemodynamic data, peripheral oxygen saturation, and respiratory rate were recorded perioperatively. Recovery time, time to discharge, and comfort score were noted.
Chi-square (χ2) test was used for categorical data. Student's t-test was used for quantitative variables for comparison between the two groups. For intragroup comparison, paired t-test was used. SPSS 14.0 was used for analysis.
Although the heart rate was comparable, blood pressures were consistently higher in group PK. Postoperative nausea and vomiting and delay in voiding were more frequent in group PK (P<0.05). The time to reach Aldrete score ≥8 was significantly longer in group PK (11.14±3.29 min in group PF vs. 17.3±6.32 min in group PK, P<0.01). The time to discharge was significantly longer in group PK (105.8±13.07 min in group PF vs.138.18±13.20 min in group PK, P<0.01). Patient comfort and acceptability was better in group PF, P<0.01).
As compared to ketamine-propofol, fentanyl–propofol combination is associated with faster recovery, earlier discharge, and better patient acceptability.
Intravenous sedation; ketamine; laparoscopic tubal ligation; local anesthesia; propofol
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.
Institutional Review Board of Buddhist Tzu Chi General Hospital (IRB097-18) and Chinese Clinical Trial Registry (ChiCTR-TRC-12002575)
Balanced propofol sedation; Alfentanil; Fentanyl; Deep sedation; Diagnostic endoscopy; Cost benefit
To assess the efficacy and safety of propofol sedation for gastrointestinal endoscopy, we conducted a meta-analysis of randomized controlled trials (RCTs) comparing propofol with traditional sedative agents.
RCTs comparing the effects of propofol and traditional sedative agents during gastrointestinal endoscopy were found on MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE. Cardiopulmonary complications (i.e., hypoxia, hypotension, arrhythmia, and apnea) and sedation profiles were assessed.
Twenty-two original RCTs investigating a total of 1,798 patients, of whom 912 received propofol only and 886 received traditional sedative agents only, met the inclusion criteria. Propofol use was associated with shorter recovery (13 studies, 1,165 patients; WMD –19.75; 95% CI –27.65, 11.86) and discharge times (seven studies, 471 patients; WMD –29.48; 95% CI –44.13, –14.83), higher post-anesthesia recovery scores (four studies, 503 patients; WMD 2.03; 95% CI 1.59, 2.46), better sedation (nine studies, 592 patients; OR 4.78; 95% CI 2.56, 8.93), and greater patient cooperation (six studies, 709 patients; WMD 1.27; 95% CI 0.53, 2.02), as well as more local pain on injection (six studies, 547 patients; OR 10.19; 95% CI 3.93, 26.39). Effects of propofol on cardiopulmonary complications, procedure duration, amnesia, pain during endoscopy, and patient satisfaction were not found to be significantly different from those of traditional sedative agents.
Propofol is safe and effective for gastrointestinal endoscopy procedures and is associated with shorter recovery and discharge periods, higher post-anesthesia recovery scores, better sedation, and greater patient cooperation than traditional sedation, without an increase in cardiopulmonary complications. Care should be taken when extrapolating our results to specific practice settings and high-risk patient subgroups.
Endotracheal intubation has been performed during the administration of Propofol anaesthesia without neuromuscular blockade. In the study, we have assessed tracheal intubating conditions and haemodynamic responses in children aged 4 to12 years by using combination of either Fentanyl and Propofol; or Propofol and a neuromuscular blocker, suxamethonium. Intubating conditions were assessed on a 1-4 scale based on ease of laryngoscopy, position of vocal cords, degree of coughing and jaw relaxation. Tracheal intubation was successful in 95% of patients receiving Fentanyl-Propofol and 100% of patients receiving Propofol-suxamethonium. Fentanyl-Propofol provided better haemodynamic stability than Propofol-suxamethonium. We conclude that Propofol-Fentanyl combination could be a useful alternative technique for tracheal intubation when neuromuscular blocking drugs are contraindicated or need to be avoided.
Endotracheal intubation; Fentanyl; Propofol; suxamethonium
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.
Endoscopy; Deep sedation; Anesthetic administration; Anesthetic dose; Adverse effects
Propofol is the most commonly using intravenous hypnotic for the induction and maintenance of general anesthesia. However, pain on propofol injection is a well known adverse event. Currently, acute and chronic pain can be controlled by utilizing the "gate control" theory.
Patients were randomized to receive lidocaine (0.5 mg/kg; Group L), touch on IV injection site (Group T), combination lidocaine (0.5 mg/kg) and touch on IV injection site (Group B), or normal saline (Group S) with venous occlusion for 1 minute, followed by administration of propofol (0.5 mg/kg) into the largest dorsal vein of the hand. Immediately after administering propofol, an investigator blinded to the group assignments asked the patient about pain at the injection site and assessed pain intensity using a 4-point verbal rating scale (0 = none, 1 = mild, 2 = moderate, 3 = severe).
A significant decrease in the incidence of pain on propofol injection was achieved in group L (37%) and group B (23%) compared to either group T (80%) and group S (83%) (P < 0.001). But, the incidence of moderate and severe pain was significantly lower in group L (7%), group T (20%) and group B (0%) when compared to group S (53%) (P < 0.05).
Light touch and rubbing reduced pain, although while, they did not reduce the incidence of pain, they reduced the intensity of pain. This method might be considered as an alternative to other treatments but may be contraindicated for use with other drugs.
Lidocaine; Pain; Propofol; Touch
This study aimed to compare continuous intravenous infusion combinations of propofol-remifentanil and propofol-ketamine for deep sedation for surgical extraction of all 4 third molars. In a prospective, randomized, double-blinded controlled study, participants received 1 of 2 sedative combinations for deep sedation for the surgery. Both groups initially received midazolam 0.03 mg/kg for baseline sedation. The control group then received a combination of propofol-remifentanil in a ratio of 10 mg propofol to 5 μg of remifentanil per milliliter, and the experimental group received a combination of propofol-ketamine in a ratio of 10 mg of propofol to 2.5 mg of ketamine per milliliter; both were given at an initial propofol infusion rate of 100 μg/kg/min. Each group received an induction loading bolus of 500 μg/kg of the assigned propofol combination along with the appropriate continuous infusion combination . Measured outcomes included emergence and recovery times, various sedation parameters, hemodynamic and respiratory stability, patient and surgeon satisfaction, postoperative course, and associated drug costs. Thirty-seven participants were enrolled in the study. Both groups demonstrated similar sedation parameters and hemodynamic and respiratory stability; however, the ketamine group had prolonged emergence (13.6 ± 6.6 versus 7.1 ± 3.7 minutes, P = .0009) and recovery (42.9 ± 18.7 versus 24.7 ± 7.6 minutes, P = .0004) times. The prolonged recovery profile of continuously infused propofol-ketamine may limit its effectiveness as an alternative to propofol-remifentanil for deep sedation for third molar extraction and perhaps other short oral surgical procedures, especially in the ambulatory dental setting.
Propofol; Ketamine; Remifentanil; Deep sedation; TIVA
For effective postoperative antiemetic management in pediatric moyamoya disease patients receiving fentanyl based postoperative analgesia, a multimodal approach has been recommended. The uncertain efficacy of ondansetron for pediatric neurosurgical patients or the possible antiemetic effect of small dose of propofol motivated us to evaluate the preventive effect of a subhypnotic dose of propofol combined with dexamethasone on postoperative vomiting (POV), especially during immediate postoperative periods.
In a prospective observer-blind randomized controlled study, we compared dexamethasone 0.15 mg/kg alone (Group D) with dexamethasone combined with propofol of 0.5 mg/kg (Group DP) in 60 pediatric patients, aged 4-17 years, who underwent indirect bypass surgery and received fentanyl-based postoperative analgesia. Occurrence of vomiting and pain score (Wong-Baker facial score) and requirement of rescue analgesic and antiemetic were continually measured (0-2, 2-6, 6-12 and 12-24 postoperative hours). For statistical analysis, in addition to the Fisher's exact test, a generalized linear mixed model (GLMM) and the linear mixed model (LMM) for repeated measures were used for vomiting and pain scores, respectively.
There was no statistical significance of POV incidence, requirement of rescue analgesic and pain score between the two groups at any measured intervals. The incidence of POV was 53.3% during 24 hours in both groups, and was especially 6.7% and 13.3% (P = 0.671) during 0-2 hr and 16.7% and 23.3% (P = 0.748) during 2-6 hr in group D and group DP, respectively.
A small dose of propofol combined with dexamethasone appears ineffective to preventing POV in pediatric moyamoya patients receiving continuous fentanyl infusion.
Dexamethasone; Moyamoya disease; Postoperative vomiting; Propofol
Despite preclinical evidence suggesting a synergistic interaction between ketamine and opioids promoting analgesia, several clinical trials have not identified dosing regimens capable of eliciting a benefit in the co-administration of ketamine with opioids.
Ten healthy volunteers participated in a double blinded, randomised, placebo controlled, crossover laboratory study in order to determine whether a low dose of ketamine potentiated the antinociceptive effect of fentanyl without causing an increase in sedative effects. A battery of tests was used to assess both nociception and sedation including electrical current, pressure, thermal stimuli, psychometric tests, and both subjective and objective scores of sedation. Target controlled infusions of the study drugs were used. Ketamine and fentanyl were administered alone and in combination in a double-blinded randomised crossover design. Saline was used as the control, and propofol was used to validate the tests of sedation. Cardiovascular and respiratory parameters were also assessed.
The electrical current pain threshold dose response curve of fentanyl combined with ketamine was markedly steeper than the dose response curve of fentanyl alone. While a ketamine serum concentration of 30 ng/ml did not result in a change in electrical pain threshold when administered alone, when it was added to fentanyl, the combination resulted in greater increase in pain threshold than that of fentanyl administered alone. When nociception was assessed using heat and pressure stimuli, ketamine did not potentiate the anti-nociceptive effect of fentanyl. There was no difference between the sedative effect of fentanyl and fentanyl in combination with ketamine as assessed by both subjective and objective measures of sedation. Cardiovascular and respiratory parameters were unaffected by the study drugs at the doses given.
A serum concentration of ketamine that did not alter indices of sedation potentiated the antinociceptive effect of fentanyl. This potentiation of antinociception occurred without an increase in sedation suggesting that low steady doses of ketamine (30–120 ng/ml) might be combined with μ opioid agonists to improve their analgesic effect in a clinical setting. (296 words)
This study examined the safety and effectiveness of the procedural sedation analgesia (PSA) technique carried out in the emergency department (ED) of a university hospital over a period of 1 year. The research was done to compare the effectiveness and efficacy of moderate sedation of fentanyl combined with either midazolam or propofol for any brief, intense procedure in the ED setting.
The objectives were to observe the occurrence of adverse events in subjects undergoing PSA for intense and painful procedures in the emergency department and to implement the use of capnography as a method of monitoring the patients when they were under PSA.
Forty patients were selected for this study. They were randomly divided into two equal groups using the computer-generated random permuted blocks of four patients. Twenty patients were grouped together as group A and the remaining 20 patients as group B. Drugs used were single blinded to prevent any bias. Drug A was propofol and fentanyl, while drug B was midazolam and fentanyl. The procedures involved included orthopedic manipulation such as reduction of fractures, reduction of dislocated joints, abscess drainage, wound debridement, laceration wound repair and cardioversion. All of the subjects were monitored for their vital signs and end tidal carbon dioxide level every 10 min till the PSA was completed. The duration of stay in the ED was documented when the subjects had completed the procedure and were released from the department.
Of the study population, 75.6% were males. The mean age was 37.8 years (95% CI 33.2, 39.8). None of the patients developed any major complications while under PSA. The vital signs pre-, intra- and post-procedure were not significantly different in either the propofol or mizadolam groups (p value >0.05).
This study had proven that there was no difference in adverse event occurrence between the studied drugs during PSA. Propofol can be recommended for use in PSA if the operator is well trained and familiar with the drug.
Procedural sedation analgesia; Midazolam; Propofol; Emergency department
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.
Morbidly obese; Bariatric; Propofol; Total intravenous anesthesia; Bispectral index; Anesthetic depth; Pediatric; Adolescents
The induction dose of propofol is reduced with concomitant use of opioids as a result of a possible synergistic action.
Aim and Objectives:
The present study compared the effect of fentanyl and two doses of butorphanol pre-treatment on the induction dose of propofol, with specific emphasis on entropy.
Three groups of 40 patients each, of the American Society of Anaesthesiologistsphysical status I and II, were randomized to receive fentanyl 2 μg/kg (Group F), butorphanol 20 μg/kg (Group B 20) or 40 μg/kg (Group B 40) as pre-treatment. Five minutes later, the degree of sedation was assessed by the observer's assessment of alertness scale (OAA/S). Induction of anesthesia was done with propofol (30 mg/10 s) till the loss of response to verbal commands. Thereafter, rocuronium 1 mg/kg was administered and endotracheal intubation was performed 2 min later. OAA/S, propofol induction dose, heart rate, blood pressure, oxygen saturation and entropy (response and state) were compared in the three groups.
Data was analyzed using ANOVA test with posthoc significance, Kruskal–Wallis test, Chi-square test and Fischer exact test. A P<0.05 was considered as significant.
The induction dose of propofol (mg/kg) was observed to be 1.1±0.50 in Group F, 1.05±0.35 in Group B 20 and 1.18±0.41 in Group B40. Induction with propofol occurred at higher entropy values on pre-treatment with both fentanyl as well as butorphanol. Hemodynamic variables were comparable in all the three groups.
Butorphanol 20 μg/kg and 40 μg/kg reduce the induction requirement of propofol, comparable to that of fentanyl 2 μg/kg, and confer hemodynamic stability at induction and intubation.
Butorphanol; entropy; fentanyl; propofol
To compare two different doses of propofol for laryngeal mask airway (LMA) insertion in children undergoing out-patient surgeries.
Insertion of LMA just after anesthesia induction is facilitated using propofol. However, the optimal dose of this drug not determined yet as heavy doses may lead to severe complications, whereas lower doses may not be quite as effective.
In a double-blind randomized clinical trial, 120 children undergoing out-patient surgeries were recruited to receive intravenous propofol at a dose of either 2.5 mg/kg (group 1) or 3.5 mg/kg (group 2) for induction. Intravenous midazolam (0.03 mg/kg) and fentanyl (1 μg/kg) were used as pre-medication in all patients and anesthesia induction was initiated using lidocaine (1 mg/kg) prior to propofol administration. Hemodynamic changes, probable complications, quality of the established airway and number of attempts for LMA insertion were compared between two groups.
There were no differences in systolic and diastolic blood pressure, heart rate, peripheral oxygen saturation and intraoperative complications between the groups (P>0.05). LMA insertion was successful at the first attempt in 55 (93.2%) and 54 (91.5%) cases in group 1 and group 2, respectively (P>0.05). The efficiency of the established airways was adequate in all the patients of both groups.
It seems that propofol doses of 2.5 and 3.5 mg/kg are equally effective for LMA insertion following intravenous midazolam, fentanyl, and lidocaine.
Children; laryngeal mask airway; propofol
The use of propofol for palliative sedation of children is not well documented.
Here we describe our experience with the use of propofol palliative sedation therapy (PST) to alleviate intractable end-of-life suffering in three pediatric oncology patients, and propose an algorithm for the selection of such candidates for PST.
Patients and Methods
We identified inpatients who had received propofol PST within 20 days of death at our institution between 2003 and 2010. Their medical records were reviewed for indicators of pain, suffering, and sedation from 48 hours before PST to the time of death. We also tabulated consumption of opioids and other symptom management medications, pain scores, and adverse events of propofol, and reviewed clinical notes for descriptors of suffering and/or palliation.
Three of 192 (1.6%) inpatients (aged 6–15 years) received propofol PST at the end of life. Consumption of opioids and other supportive medications decreased during PST in two cases. In the third case, pain scores remained high and sedation was the only effective comfort measure. Clinical notes suggested improved comfort and rest in all patients. Propofol infusions were continued until the time of death.
Our experience demonstrates that propofol PST is a useful palliative option for pediatric patients experiencing intractable suffering at the end of life. We describe an algorithm that can be used to identify such children who are candidates for PST.
The death of a patient under sedation in New South Wales, Australia, in 2002 has again raised the question of the safety of dental sedation. This study sought answers to 2 questions: Can safe oxygen saturation levels (≥94%) be consistently maintained by a single operator/sedationist? Does the additional use of propofol, in subanesthetic doses, increase the risk of exposure to hypoxemia? Three thousand five hundred cases generated between 1996 and 2006 were randomly examined and divided into 2 subcohorts: 1750 patients were sedated with midazolam and fentanyl, and 1750 patients received propofol, in subanesthetic increments, in addition to midazolam and fentanyl. Initial sedation was established using midazolam and fentanyl in both subcohorts. The second subcohort received propofol during times of noxious stimulation. Patient exposure to 2 or more oxygen desaturations below 94% was uncommon. The variables that were significantly associated with low saturations were age, gender, and weight. Neither the dose of midazolam nor the additional use of propofol was a significant risk factor. ASA classification (I or II) was not a determinant of risk. The data, within the limitations of the study, showed that a single operator/sedationist, supported by a well-trained team of nurses, can consistently maintain safe oxygen saturation levels. The additional use of propofol did not increase exposure to hypoxemia.
Dental sedation; Safe oxygen saturation levels; Propofol
Aim & objective
To find if direct laryngoscopy (DL) could be done without using succinylcholine and secondly, to acertain the appropriate anesthetic regimen.
Patients and methods
In a double blind placebo controlled study 67 patients aged 40–75 years of age, of both sex requiring direct laryngoscopy (DL) either for diagnosis or for biopsy were enrolled. The patients were randomly divided in three groups. The patients in group F and S received Fentanyl or Sufentanil respectively along with Propofol, whereas those in group N received normal saline (placebo) and propofol. The conditions of laryngoscopy, hemodynamic parameters and any adverse events were recorded. Good or fair conditions for laryngoscopy were achieved in 91% (21), 87% (19) and 73% (16) of patients in groups F, S and N respectively (p < 0.05) in favor of group F and S. During DL arterial pressure and pulse rate changes were minimal when propofol was administered along with opioids, (group F and S) compared to group N where only propofol was used.
No serious side effects were seen in the three groups. Hence by these findings we concluded that better conditions of DL are achieved during anesthesia with propofol and fentanyl and sufentanil alone. The opioids provided additional benefit of stable hemodynamics.
Direct Laryngoscopy; Propofol; Fentanyl; Sufentanil; Hemodynamic changes
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.
analgesia; analgesia based sedation; critical care; fentanyl; propofol; remifentanil; renal function; sedation
This article details a double-blind, randomized, placebo-controlled pilot study evaluating the analgesic efficacy and clinical acceptability of intravenous tramadol in patients undergoing surgical removal of an impacted third molar tooth under local anesthesia and intravenous sedation with propofol. Forty-five ASA status 1 dental outpatients were randomly allocated to 2 groups of 22 (group A) and 23 (group B) patients each (n = 45). Group A (T/P) received intravenous tramadol 1.5 mg/kg injected over 2 minutes, followed by a bolus dose of intravenous propofol 0.4 mg/ kg. Maintenance consisted of a continuous infusion of propofol 3 mg/kg/h, with an additional bolus dose of 0.4 mg/kg intravenously 2-3 minutes prior to the infiltration of the local anesthetic solution. Group B (P/P) patients received no tramadol but instead a saline placebo solution and an identical amount of propofol. Overall, in this study, postoperative pain was much better controlled in the group receiving tramadol 1.5 mg/kg intravenously despite there being no significant difference in the dose of propofol administered in both groups. Intravenous tramadol, when given with propofol, did not affect the cardiovascular, respiratory, and sedative effects of propofol. Following tramadol, despite being an opioid, no nausea and vomiting were reported in the early postoperative period, indicating the value of using tramadol with propofol. Thus, this pilot study demonstrated the potential use of intravenous tramadol with propofol in day-case dento-alveolar surgery.
For proper sedation during endoscopic submucosal dissection (ESD), propofol has been widely used. This study aimed to compare the levels of sedation and tolerance of patients treated with midazolam (M group) and a combination of midazolam and propofol (MP group) during ESD.
A total of 44 consecutive patients undergoing ESD were randomly assigned to the two groups. In the M group, 2 mg of midazolam was given repeatedly to maintain after a loading dose of 5 mg. The MP group initially received 5 mg of midazolam and 20 mg of propofol. Then, we increased the dosage of propofol by 20 mg gradually.
The average amount of midazolam was 12 mg in the M group. In the M group, 10 patients were given propofol additionally, since they failed to achieve proper sedation. The average amount of propofol was 181 mg in the MP group. Procedure time, vital signs and rates of complications were not significantly different between two groups. Movement of patients and discomfort were lower in the MP group.
During ESD, treatment with propofol and a low dose of midazolam for sedation provides greater satisfaction for endoscopists
compared to midazolam alone.
Endoscopic submucosal dissection; Sedation; Midazolam; Propofol
Fentanyl-induced cough is not an uncommon condition during the induction of general anesthesia. A preliminary randomized controlled study was designed to observe the effects of different priming doses of propofol on fentanyl-induced cough during anesthesia induction. A total of 120 patients were randomized into 4 groups (n = 30) to receive the intravenous injection of intralipid (group I), propofol 1 mg·kg-1 (group II), propofol 1.5 mg·kg-1 (group III), or propofol 2 mg·kg-1 (group IV) 1 minute before a bolus of fentanyl 2.5 µg·kg-1. The occurrence and severity of cough were recorded for 2 minutes after fentanyl bolus. The severity of cough was graded as none (grade 0), mild (grade 1–2), moderate (grade 3–4), or severe (grade 5 or more). The average bolus time of fentanyl was 1.5 ± 0.3 seconds in the present study. The incidence of fentanyl-induced cough was 80.0% in group I, 40.0% in group II, 6.7% in group III, and 3.3% in group IV, respectively. Groups II, III, and IV had a lower incidence and less severity of cough than group I (P < 0.05). Groups III and IV had a lower incidence and less severity of cough than group II (P < 0.05). In summary, a priming dose of more than 1 mg·kg-1 of propofol is effective to suppress fentanyl-induced cough in a dose-dependent manner. We suggest using a priming dose of propofol 1.5 mg·kg-1 to suppress cough during the anesthesia induction with propofol and fentanyl in clinical practice.
Anesthesia; cough; dose; fentanyl; propofol
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.
Upper gastrointestinal endoscopy; Adverse events; Sedation; Monitoring; Chronic obstructive pulmonary disease
Endoscopic submucosal dissection (ESD) is accepted as a treatment for gastric neoplasms and usually requires deep sedation. The aim of this study was to evaluate the safety and efficacy profiles of deep sedation induced by continuous propofol infusion with or without midazolam during ESD.
A total of 135 patients scheduled for ESDs between December 2008 and June 2010 were included in this prospective study and were randomly assigned to one of two groups: the propofol group or the combination group (propofol plus midazolam).
The propofol group reported only one case of severe hypoxemia with no need of mask ventilation or intubation. Additionally, 18 cases of mild hypotension were observed in the propofol group, and 11 cases were observed in the combination group. The combination group had a lower mean total propofol dose (378 mg vs 466 mg, p<0.012), a longer mean recovery time (10.5 minutes vs 7.9 minutes, p=0.027), and a lower frequency of overall adverse events (32.8% vs 17.6%, p=0.042).
Deep sedation induced by continuous propofol infusion was shown to be safe during ESD. The combination of continuous propofol infusion and intermittent midazolam injection can decrease the total dose and infusion rate of propofol and the overall occurrence of adverse events.
Deep sedation; Propofol; Midazolam; Endoscopy; Gastrointestinal
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.
computed tomography; endoscopy; gastrointestinal; magnetic resonance imaging; pediatrics; propofol
AIM: To assess the efficacy and safety of a balanced approach using midazolam in combination with propofol, administered by non-anesthesiologists, in a large series of diagnostic colonoscopies.
METHODS: Consecutive patients undergoing diagnostic colonoscopy were sedated with a single dose of midazolam (0.05 mg/kg) and low-dose propofol (starter bolus of 0.5 mg/kg and repeated boluses of 10 to 20 mg). Induction time and deepest level of sedation, adverse and serious adverse events, as well as recovery times, were prospectively assessed. Cecal intubation and adenoma detection rates were also collected.
RESULTS: Overall, 1593 eligible patients were included. The median dose of propofol administered was 70 mg (range: 40-120 mg), and the median dose of midazolam was 2.3 mg (range: 2-4 mg). Median induction time of sedation was 3 min (range: 1-4 min), and median recovery time was 23 min (range: 10-40 min). A moderate level of sedation was achieved in 1561 (98%) patients, whilst a deep sedation occurred in 32 (2%) cases. Transient oxygen desaturation requiring further oxygen supplementation occurred in 8 (0.46%; 95% CI: 0.2%-0.8%) patients. No serious adverse event was observed. Cecal intubation and adenoma detection rates were 93.5% and 23.4% (27.8% for male and 18.5% for female, subjects), respectively.
CONCLUSION: A balanced sedation protocol provided a minimalization of the dose of propofol needed to target a moderate sedation for colonoscopy, resulting in a high safety profile for non-anesthesiologist propofol sedation.
Colonoscopy; Propofol; Sedation
Fospropofol disodium is a water-soluble prodrug of propofol. A subset analysis was undertaken of elderly patients (≥65 y) undergoing flexible bronchoscopy, who were part of a larger multicenter, randomized, double-blind study.
Patients received fentanyl citrate (50 mcg) followed by fospropofol at initial (4.88mg/kg) and supplemental (1.63mg/kg) doses. The primary end point was sedation success (3 consecutive Modified Observer's Assessment of Alertness/Sedation scores of ≤4 and procedure completion without alternative sedative or assisted ventilation). Treatment success, time to fully alert, patient and physician satisfaction, and safety/tolerability were also evaluated.
In the elderly patients subset (n=61), sedation success was 92%, the mean time to fully alert was 8.0±10.9 min, and memory retention was 72% during recovery, and these were comparable with the younger patients subgroup (age, <65 y). Sedation-related adverse events occurred in 23% of the elderly and 18% of the younger patients (age, <65 y) group. Hypoxemia occurred in 26% of the elderly and 18% of the younger patients group, but no escalation of care was required.
Fospropofol provided safe and effective sedation, rapid time to fully alert, and high satisfaction in this elderly subset undergoing flexible bronchoscopy, which was comparable with outcomes in younger patients.
bronchoscopy; elderly; fospropofol; sedation