Target-controlled infusion (TCI) provides precise pharmacokinetic control of propofol concentration in the effect-site (Ce), eg. brain. This pilot study aims to evaluate the feasibility and optimal TCI regimen for flexible bronchoscopy (FB) sedation.
After alfentanil bolus, initial induction Ce of propofol was targeted at 2 μg/ml. Patients were randomized into three titration groups (i.e., by 0.5, 0.2 and 0.1 μg/ml, respectively) to maintain stable sedation levels and vital signs. Adverse events, frequency of adjustments, drug doses, and induction and recovery times were recorded.
The study was closed early due to significantly severe hypoxemia events (oxyhemoglobin saturation <70%) in the group titrated at 0.5 μg/ml. Forty-nine, 49 and 46 patients were enrolled into the 3 respective groups before study closure. The proportion of patients with hypoxemia events differed significantly between groups (67.3 vs. 46.9 vs. 41.3%, p = 0.027). Hypotension events, induction and recovery time and propofol doses were not different. The Ce of induction differed significantly between groups (2.4±0.5 vs. 2.1±0.4 vs. 2.1±0.3 μg/ml, p = 0.005) and the Ce of procedures was higher at 0.5 μg/ml titration (2.4±0.5 vs. 2.1±0.4 vs. 2.2±0.3 μg/ml, p = 0.006). The adjustment frequency tended to be higher for titration at 0.1 μg/ml but was not statistically significant (2 (0∼6) vs. 3 (0∼6) vs. 3 (0∼11)). Subgroup analysis revealed 14% of all patients required no further adjustment during the whole sedation. Comparing patients requiring at least one adjustment with those who did not, they were observed to have a shorter induction time (87.6±34.9 vs. 226.9±147.9 sec, p<0.001), a smaller induction dose and Ce (32.5±4.1 vs. 56.8±22.7 mg, p<0.001; 1.76±0.17 vs. 2.28 ±0.41, p<0.001, respectively), and less hypoxemia and hypotension (15.8 vs.56.9%, p = 0.001; 0 vs. 24.1%, p = 0.008, respectively).
Titration at 0.5 μg/ml is risky for FB sedation. A subgroup of patients required no more TCI adjustment with fewer complications. Further studies are warranted to determine the optimal regimen of TCI for FB sedation.
Correlation between the clinical and electroencephalogram-based monitoring has been documented sporadically during the onset of sedation. Propofol and midazolam have been studied individually using the observer's assessment of awareness/sedation (OAA/S) score and Bispectral index score (BIS). The present study was designed to compare the time to onset of sedation for propofol and midazolam using both BIS and OAA/S scores, and to find out any correlation.
A total of 46 patients (18-60 years, either sex, American Society of Anesthesiologists (ASA) I/II) posted for infraumbilical surgeries under spinal anaesthesia were randomly allocated to receive either injection propofol 1 mg/kg bolus followed by infusion 3 mg/kg/h (Group P, n=23) or injection midazolam 0.05 mg/kg bolus followed by infusion 0.06 mg/kg/h (Group M, n=23). Spinal anaesthesia was given with 2.5 ml to 3.0 ml of 0.5% bupivacaine heavy. When sensory block reached T6 level, sedation was initiated. The time to reach BIS score 70 and time to achieve OAA/S score 3 from the start of study drug were noted. OAA/S score at BIS score 70 was noted. Data from 43 patients were analyzed using SPSS 12 for Windows.
Time to reach BIS score 70 using propofol was significantly lower than using the midazolam (P<0.05). Time to achieve OAA/S score 3 using propofol was comparable with midazolam (P=0.358).
A divergence exists between the time to reach BIS score 70 and time to achieve OAA/S score 3 using midazolam, compared with propofol, during the onset of sedation.
Bispectral index score; midazolam; observer's assessment of awareness/sedation score; propofol; sedation
Regional anaesthesia has become an important anaesthetic technique. Effective sedation is an essential for regional techniques too. This study compares midazolam and propofol in terms of onset & recovery from sedation, dosage and side effects of both the drugs using Bispectral Index monitoring. Ninety eight patients were randomly divided into two groups,one group recieved midazolam infusion while the other recieved propofol infusion until BIS reached 75. We observed Time to reach desired sedation, HR, MABP, time for recovery, dose to reach sedation and for maintenance of sedation and side effects if any. The time to reach required sedation was 11 min in Midazolam group(Group I) while it was 6 min in Propofol group(Group II) (p=0.0). Fall in MABP was greater with propofol. Recovery in with midazolam was slower than with propofol (18.6 ± 6.5 vs 10.10±3.65 min) (p=0.00). We concluded that both midazolam and propofol are effective sedatives, but onset and offset was quicker with propofol, while midazolam was more cardiostable.
Propofol; Midazolam; Sedation; BIS
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
Propofol sedation for endoscopic retrograde cholangiopancreatography (ERCP) procedures is a popular current technique that has generated controversy in the medical field. Worldwide, both anesthetic and nonanesthetic personnel administer this form of sedation. Although the American and Canadian societies of gastroenterologists have endorsed the administration of propofol by nonanesthesia personnel, the US Food and Drug Administration (FDA) has not licensed its use in this manner. There is some evidence for the safe use of propofol by nonanesthetic personnel in patients undergoing endoscopy procedures, but there are few randomized trials addressing the safety and efficacy of propofol in patients undergoing ERCP procedures. A serious possible consequence of propofol sedation in patients is that it may result in rapid and unpredictable progression from deep sedation to general anesthesia, and skilled airway support may be required as a rescue measure. Potential complications following deep propofol sedation include hypoxemia and hypotension. Propofol sedation for ERCP procedures is an area of clinical practice where discussion and mutual cooperation between anesthesia and nonanesthesia personnel may enhance patient safety.
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.
Cocktail sedation containing propofol; Meperidine; Midazolam; ERCP
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
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
Appropriate sedation benefits patients by reducing the stress response, but it requires an appropriate method of assessment to adjust the dosage of sedatives. The aim of this study was to compare the difference in the sedation of mechanically ventilated patients undergoing flexible bronchoscopy (FB) monitored by auditory-evoked potentials (AEPs) or the Ramsay sedation scale (RSS).
In a prospective, randomized, controlled study, all patients who underwent FB with propofol sedation were monitored and their sedation adjusted. During FB, one group was monitored by AEP and another group was monitored by RSS. The propofol dosage was adjusted by the nursing staff during examination to maintain the Alaris AEP index (AAI) value between 25 and 40 in the AEP group and the RSS at 5 or 6 in the RSS group. Before FB and during FB, the AAI, heart rate (HR), and mean arterial pressure (MAP) were recorded every 5 min. The percentages of time at the sedation target and the propofol dosages were calculated.
Nineteen patients received AEP monitoring and 18 patients received RSS monitoring. The percentage of time at the sedation target during FB was significantly higher in the AEP monitoring group (51.3%; interquartile range [IQR], 47.0–63.5%) than in the RSS group (15.4%; IQR, 9.5–23.4%), (P < 0.001). During FB, the RSS group had a significantly higher AAI (P = 0.011), HR (P < 0.001), and MAP (P < 0.001) than the AEP group.
In mechanically ventilated patients undergoing FB, AEP monitoring resulted in less variation in AAI, HR, and MAP, and a higher percentage of time at the sedation target than RSS monitoring.
Auditory-evoked potential; Bronchoscopy; Critical care; Ramsay sedation score; Sedation
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 whether monitoring sedation status using bispectral index (BIS) as an adjunct to clinical evaluation was associated with a reduction in the total amount of sedative drug used in a 12 h period.
Prospective randomized controlled clinical trial.
Tertiary care neurocritical care unit.
Sixty-seven mechanically ventilated adult patients receiving continuous intravenous sedation with propofol.
Sedation monitoring using clinical assessment with the Ramsay scale (Ramsay-alone group) or clinical assessment plus BIS monitoring (BIS-augmentation group). Subjects were randomized to Ramsay-alone (n = 35), or BIS-augmentation (n = 32). Nurses adjusted the dose of propofol to a Ramsay of 4, or a Ramsay of 4 and BIS between 60 and 70.
Measurements and Main Results
Patients in the BIS-augmentation group received significantly less propofol by volume (93.5 ml vs. 157.8 ml, respectively; P < .015), and had lower infusion rates (14.6 vs. 27.9 mcg/kg/min; P = .003). There is a lower risk of propofol infusion exceeding manufacturer’s recommended dosing guides in the BIS-augmentation group versus the Ramsay-alone group (0 vs. 23%, P = .0052). The BIS-augmentation group woke up much quicker than those in the Ramsay-alone group (1.2 vs. 7.5 min; P < .0001).
BIS-augmented sedation monitoring resulted in a marked reduction in the total dose of sedative used to achieve the same level of clinical sedation resulting in shortened time to wake up without any measurable adverse effects. Physiologic sedation assessment tools may provide a useful means of improving the care of sedated critically ill patients.
Sedation assessment; Nursing care; Critical care; Neurofunction monitoring; Neurocritical care
Objective: To compare the effects of epidural anesthesia with 1.5% lidocaine and 0.5% ropivacaine on propofol requirements, the time to loss of consciousness (LOC), effect-site propofol concentrations, and the hemodynamic variables during induction of general anesthesia guided by bispectral index (BIS) were studied. Methods: Forty-five patients were divided into three groups to receive epidurally administered saline (Group S), 1.5% (w/w) lidocaine (Group L), or 0.5% (w/w) ropivacaine (Group R). Propofol infusion was started to produce blood concentration of 4 μg/ml. Once the BIS value reached 40~50, endotracheal intubation was facilitated by 0.1 mg/kg vecuronium. Measurements included the time to LOC, effect-site propofol concentrations, total propofol dose, mean arterial blood pressure (MABP), and heart rate (HR) at different study time points. Results: During induction of anesthesia, both Groups L and R were similar for the time to LOC, effect-site propofol concentrations, total propofol dose, MABP, HR, and BIS. The total doses of propofol administered until 1 min post-intubation were significantly less in patients of Groups R and L compared with Group S. MABP and HR were significantly lower following propofol induction compared with baseline values in the three groups, or MABP was significantly increased following intubation as compared with that prior to intubation in Group S but not in Groups R and L while HR was significantly increased following intubation in the three groups. Conclusion: Epidural anesthesia with 1.5% lidocaine and 0.5% ropivacaine has similar effects on the time to LOC, effect-site propofol concentrations, total propofol dose, and the hemodynamic variables during induction of general anesthesia.
Propofol; Lidocaine; Ropivacaine; Epidural anethesia; Bispectral index
AIM: To determine whether bispectral index (BIS) monitoring is useful for propofol administration for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP).
METHODS: Fifty-nine consecutive patients with a variety of reasons for ERCP who underwent the procedure at least twice between 1 July 2010 and 30 November 2010. This was a randomized cross-over study, in which each patient underwent ERCP twice, once with BIS monitoring and once with control monitoring. Whether BIS monitoring was done during the first or second ERCP procedure was random. Patients were intermittently administered a mixed regimen including midazolam, pethidine, and propofol by trained nurses. The nurse used a routine practice to monitor sedation using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale or the BIS monitoring. The total amount of midazolam and propofol used and serious side effects were compared between the BIS and control groups.
RESULTS: The mean total propofol dose administered was 53.1 ± 32.2 mg in the BIS group and 54.9 ± 30.8 mg in the control group (P = 0.673). The individual propofol dose received per minute during the ERCP procedure was 2.90 ± 1.83 mg/min in the BIS group and 3.44 ± 2.04 mg in the control group (P = 0.103). The median value of the MOAA/S score during the maintenance phase of sedation was comparable for the two groups. The mean BIS values throughout the procedure (from insertion to removal of the endoscope) were 76.5 ± 8.7 for all 59 patients in using the BIS monitor. No significant differences in the frequency of < 80% oxygen saturation, hypotension (< 80 mmHg), or bradycardia (< 50 beats/min) were observed between the two study groups. Four cases of poor cooperation occurred, in which the procedure should be stopped to add the propofol dose. After adding the propofol, the procedure could be conducted successfully (one case in the BIS group, three cases in the control group). The endoscopist rated patient sedation as excellent for all patients in both groups. All patients in both groups rated their level of satisfaction as high (no discomfort). During the post-procedural follow-up in the recovery area, no cases of clinically significant hypoxic episodes were recorded in either group. No other postoperative side effects related to sedation were observed in either group.
CONCLUSION: BIS monitoring trend to slighlty reduce the mean propofol dose. Nurse-administered propofol sedation under the supervision of a gastroenterologist may be considered an alternative under anesthesiologist.
Conscious sedation; Bispectral index monitors; Pancreatic neoplasm; Endoscopic retrograde cholangiopancreatography
Considering the growing trend of laryngeal surgeries and the need to protect the airway during and after surgery, among several therapeutic regimens to induce sedation, two regimens of propofol-fentanyl and propofol-midazolam were compared in microlaryngeal surgeries.
Forty ASA I-II class patients undergoing microlaryngeal surgeries and referring routinely for postoperative visits were randomly recruited into two groups. For all the patients, 0.5 mg/Kg of propofol was used as bolus and then, 50 mcg/Kg/min of the drug was infused intravenously. For one group, 0.03 mg/Kg bolus of midazolam and for the other group, 2 mcg/Kg bolus of fentanyl was administered in combination with propofol. Ramsay system was used in order to evaluate the effect of the two drugs in inducing sedation. The need for additional dose, blood pressure, heart rate, arterial blood oxygen saturation, and also recovery time and adverse effects such as nausea/vomiting and recalling intra-operative memories, were assessed.
The patients in the two groups were not statistically different regarding the number of patients, age, sex, preoperative vital signs, the need for additional doses of propofol, systolic blood pressure and mean systolic blood pressure during laryngoscopy. However, mean systolic blood pressure 1 min after removal of laryngoscope returned faster to the baseline in midazolam group (p < 0.01). Mean heart rate returned sooner to the baseline in fentanyl group following removal of stimulation. Besides, heart rate showed a more reduction following administration of fentanyl (p < 0.02). Mean arterial blood oxygen saturation during laryngoscopy significantly decreased in fentanyl group (p < 0.05) compared to the other group. The time it took to achieve a full consciousness was shorter in midazolam group (p < 0.01). Nausea/vomiting was significantly more prevalent in fentanyl group while the patients in midazolam group apparently experienced more of amnesia, comparatively (p < 0.01).
Inducing laryngeal block and local anesthesia using propofol-midazolam regimen is not only associated with a more rapid recovery and less recalling of unpleasant memories, but also better in preventing reduction of arterial oxygen saturation during laryngoscopy compared with propofol-fentanyl regimen.
Sedation; Microlaryngeal surgery; Propofol; Midazolam; Fentanyl
Even with an adequate pain assessment, critically ill patients under sedation experience pain during procedures in the intensive care unit (ICU). We evaluated the effects of adjunctive administration of Remifentanil, a short-acting drug, in deeply sedated patient on variation of Bispectral Index (BIS) during a fiberoptic bronchoscopy.
A prospective, randomized, blinded, placebo-controlled study was conducted in 18-bed ICU. Patients needing a tracheal fibroscopy under deep sedation (midazolam (0.1 mg/kg per hour) fentanyl (4 μg/kg per hour)) and neuromuscular blocking (atracurium 0.5 mg/kg) were included in the study. A continuous monitoring of BIS, arterial pressure, and heart rate were realized before, during, and after the fiberoptic exam. An adjunctive continuous placebo or Remifentanil infusion was started just before the fiberoptic exam with a target effect-site concentration of 4 ng/ml using a Base Primea pump.
Mean arterial pressure and heart rates were comparable between the placebo and Remifentanil groups at all times of the procedure. We did not observe differences in the variation of BIS values between the two groups during procedure. We described no change in BIS values relative to the placebo group in this population.
In deeply sedated and paralyzed patients, receiving analgesic support based on a scale score an additional administration of short-acting analgesic drug, such as Remifentanil, seems not to be necessary for acute pain control.
Pain; Intensive care; Bispectral index; Remifentanil
Many pathophysiologic alterations in patients with major burns can cause changes in the response of propofol. The aim of this study is to determine the appropriate induction dose of propofol using a slow infusion rate for major burn patients to obtain desirable sedation and hypnotic conditions with minimal hemodynamic changes.
45 adults with major burns and who were electively scheduled for escharectomy less than a week after injury were recruited. For induction with propofol, the patients were randomly allocated to one of two groups (group 1: 1.5 mg/kg, n = 20 and group 2: 2.0 mg/kg, n = 25). The infusion rate was 20 mg/kg/hr. The systolic and diastolic blood pressure (SBP, DBP), the heart rate, the bispectral index and the modified observers' assessment of the alertness/sedation scale (OAA/S) were measured before the induction and after the propofol infusion, as well as immediately, 3 and 5 minutes after intubation.
The SBP and DBP were significantly decreased after the propofol infusion in both group, but there were no significant differences between the two groups. The BIS values after the propofol infusion and intubation were 44.2 ± 16.1 and 43.5 ± 13.8 in group 1, and 45.6 ± 10.3 and 46.5 ± 11.4 in group 2, respectively, and there were no differences between the 2 groups.
When propofol is administrated to major burn patients, an induction dose of 1.5 mg/kg is appropriate and a slow infusion rate of 20 mg/kg/hr is safe for maintaining the desired hypnotic conditions and this dose and rate cause no significant hemodynamic problems.
Bispectral index monitors; Burns; Infusions; Intravenous; Propofol
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.
Propofol (2,6,di-isopropylphenol) was given by continuous intravenous infusion to provide sedation after cardiac surgery in 30 patients and its effects compared with those of midazolam given to a further 30 patients. Propofol infusion allowed rapid and accurate control of the level of sedation, which was satisfactory for longer than with midazolam. Patients given propofol recovered significantly more rapidly from their sedation once they had fulfilled the criteria for weaning from artificial ventilation and as a result spent a significantly shorter time attached to a ventilator. There were no serious complications in either group. Both medical and nursing staff considered the propofol infusion to be superior to midazolam in these patients. These findings suggest that propofol is a suitable replacement for etomidate and alphaxalone-alphadolone for sedating patients receiving intensive care.
This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were VC = 27.7 l, VT = 801 l, and CLD = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65·(1 − 0.00714·(SBP − 135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC50 equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light–dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night–day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients.
Propofol; Circadian rhythm; Pharmacokinetics; Pharmacodynamics; Sedation monitoring
The aim of this study was to investigate whether a small dose of midazolam and lessening the propofol dosage could prevent cardiovascular change at tracheal intubation for induction in aged patients.
Eighty patients over 65 years (ASA physical status 1, 2) scheduled for elective surgery received general anesthesia with remifentanil and propofol or midazolam. Patients in group P (n = 40) were induced with 0.9% NaCl 0.03 ml/kg, propofol 1. 2 mg/kg and remifentanil. Patients in group MP (n = 40) were induced with midazolam 0.03 mg/kg, propofol 0.8 mg/kg and remifentanil. The time taken to reach loss of consciousness (LOC) and the value of bispectral index score (BIS) at LOC were recorded. After LOC, 0.8 mg/kg of rocuronium was given and tracheal intubation was performed. The mean blood pressure (MBP) and heart rate (HR) were recorded before induction as the base value, before intubation, immediately post-intubation and 3 minutes after intubation.
Compared with the base values, MBP at before intubation and 3 minutes after intubation was significantly decreased in group P and group MP (P < 0.05). Compared with group P, the decrease of MBP was significantly less at before intubation, immediately after intubation and 3 minutes after intubation in group MP (P < 0.05). The time taken to reach LOC was significantly decreased in group MP compared with that in group P (P < 0.05). There were no significant differences of HR at any time between the two groups.
Co-induction with midazolam and propofol could prevent a marked BP decrease at tracheal intubation for induction in aged patients.
Aged; Cardiovascular system; Drug synergism; Midazolam; Propofol
Fiberoptic intubation is the gold standard technique for difficult airway management in patients of temporomandibular joint. This study was aimed to evaluate the clinical efficacy and safety of dexmedetomidine as premedication with propofol infusion for fiberoptic intubation.
Consent was obtained from 46 adult patients of temporomandibular joint ankylosis, scheduled for gap arthroplasty. They were enrolled for thisdouble-blind, randomized, prospective clinical trial with two treatment groups – Group D and Group P, of 23 patients each. Group D patients had received premedication of dexmedetomidine 1 μg/kg infused over 10 min followed by sedative propofol infusion and the control Group P patients were given only propofol infusion to achieve sedation. Condition achieved at endoscopy, intubating conditions, hemodynamic changes and postoperative events were evaluated as primary outcome.
The fiberoptic intubation was successful with satisfactory endoscopic and intubating condition in all patients. Dexmedetomidine premedication has provided satisfactory conditions for fiberoptic intubation and attenuated the hemodynamic response of fiberoptic intubation than the propofol group.
Fiberoptic intubation was found to be easier with dexmedetomidine premedication along with sedative infusion of propofol with complete amnesia of the procedure, hemodynamic stability and preservation of patent airway.
Dexmedetomidine; fiberoptic intubation; propofol; sedation
Blood-brain equilibration rate constant (ke0) is derived from either pharmacokinetic and pharmacodynamic modeling (ke0_model) or a model-independent observed time to peak effect (ke0_tpeak). Performance in bispectral index (BIS) prediction was compared between ke0_model and ke0_tpeak for microemulsion or long chain triglyceride (LCT) propofol.
Time to peak effect (tpeak, time to a maximally reduced BIS value) of microemulsion propofol after an intravenous bolus (1 mg/kg) was measured in 100 patients (group Amicro). An observed tpeak of 1.6 min for LCT propofol was obtained from an earlier study. Another 40 patients received a target controlled infusions of microemulsion propofol (ke0_model = 0.187/min, group Bmicro = 20) or LCT propofol (ke0_model = 0.26/min, group BLCT = 20) and remifentanil. The ke0_tpeak's in group Bmicro and BLCT were calculated using the observed tpeak value obtained from group Amicro and 1.6 min, respectively. Effect-site concentrations of propofol were recalculated using the amounts of propofol infused over time and ke0_tpeak's. Predicted BIS values calculated by sigmoid Emax equations with ke0_model and ke0_tpeak were compared with observed BIS values during induction and emergence for both formulations of propofol.
Observed tpeak of microemulsion propofol was 1.68 min. The median performance errors of BIS in group Bmicro were -1.83% (-24.8 to 18.9, ke0_model) and -2.42% (-26.1 to 36.2, ke0_tpeak), while 8.01% (-20.5 to 30.1, ke0_model) and 7.37% (-27.0 to 49.1, ke0_tpeak) in group BLCT. The median absolute performance errors of BIS in group Bmicro were 11.87% (2.2-31.1ke0_model) and 14.38% (-0.6 to 44.6, ke0_tpeak), while 17.31% (5.54-36.0, ke0_model) and 18.28% (-0.1 to 56.0, ke0_tpeak) in group BLCT.
The ke0_model showed better performance in BIS prediction than the ke0_tpeak.
Bispectral index; Pharmacokinetic; Propofol
This randomized study was conducted to compare the hemodynamic changes and emergence characteristics of sevoflurane versus propofol anesthesia for microlaryngeal surgery.
Forty adult patients undergoing microlaryngoscopy were randomly allocated into two groups. In propofol group, anesthesia was induced with 2-3 mg/kg propofol and maintained with propofol infusion 50-200 μg/kg/h. In sevoflurane group induction was carried out with 5-8% sevoflurane and maintained with sevoflurane in nitrous oxide and oxygen. The propofol and sevoflurane concentrations were adjusted to maintain the bispectral index of 40-60. All patients received fentanyl 2 μg/kg before induction and succinylcholine 2 mg/kg to facilitate tracheal intubation. The hemodynamic changes during induction and suspension laryngoscopy were compared. In addition, the emergence time, time to extubation, and recovery were assessed.
The changes in heart rate were comparable. The mean arterial pressure was significantly lower after induction and higher at insertion of operating laryngoscope in propofol group as compared to sevoflurane group. More patients in propofol group had episodes of hypotension and hypertension than sevoflurane group. The emergence time, extubation times, and recovery time were similar in both groups.
We found that sevoflurane showed advantage over propofol in respect of intraoperative cardiovascular stability without increasing recovery time.
General anesthesia; hemodynamic changes; microlaryngeal surgery; propofol; recovery; sevoflurane
The composite auditory evoked potentials index (cAAI) was considered a measure of overall balance between noxious stimulation, analgesia, and hypnosis; while bispectral index (BIS) shows only hypnosis, and auditory evoked potentials index (AAI) shows response to stimuli. The present study compared the performance of cAAI, BIS, and AAI in propofol-fentanyl anesthesia.
Materials and Methods:
Forty-five patients for abdominal surgery aged 30-65 years with ASA physical status I or II were randomly divided into three groups by an envelope method. Anesthesia was induced with midazolam, propofol, and fentanyl alongwith an epidural block. When hemodynamics were stable during surgery, propofol infusion rate was fixed at 4 mg/kg/h for 10 min, then increased to 6 mg/kg/h and kept it for 10 min. AAI (AEP version 1.4), cAAI (AEP version 1.6), or BIS (A-2000) was monitored in each 15 patients, and the performance of three indices was compared.
All three indices decreased significantly before intubation. Only the AAI increased significantly by intubation. During anesthesia except for at propofol 6 mg/kg/h, the cAAI was significantly higher than the AAI. Only the AAI was significantly lower at propofol 6 mg/kg/h than at 4 mg/kg/h. The cAAI had the largest and AAI had the smallest inter-individual variations. The cAAI was higher than the manufacturer's recommended range of general anesthesia.
In propofol-fentanyl anesthesia, AAI might be better to discriminate anesthetic depth than cAAI and BIS.
Auditory evoked potentials; bispectral index; electroencephalogram; fentanyl; propofol
State of the art sedation concepts on intensive care units (ICU) favor propofol for a time period of up to 72 h and midazolam for long-term sedation. However, intravenous sedation is associated with complications such as development of tolerance, insufficient sedation quality, gastrointestinal paralysis, and withdrawal symptoms including cognitive deficits. Therefore, we aimed to investigate whether sevoflurane as a volatile anesthetic technically implemented by the anesthetic-conserving device (ACD) may provide advantages regarding ‘weaning time’, efficiency, and patient’s safety when compared to standard intravenous sedation employing propofol.
This currently ongoing trial is designed as a two-armed, monocentric, randomized prospective phase II study including intubated intensive care patients with an expected necessity for sedation exceeding 48 h. Patients are randomly assigned to either receive intravenous sedation with propofol or sevoflurane employing the ACD. Primary endpoint is the comparison of the ‘weaning time’ defined as the time required from discontinuation of the sedating agent until sufficient spontaneous breathing occurs. Moreover, sedation depth evaluated by Richmond Agitation Sedation Scale and parameters of patient’s safety (that is, vital signs, laboratory monitoring of organ function) as well as the duration of mechanical ventilation and overall stay on the ICU are analyzed and compared. An intention-to-treat analysis will be carried out with all patients for whom it will be possible to define a wake-up time. In addition, a per-protocol analysis is envisaged. Completion of patient recruitment is expected by the end of 2012.
This clinical study is designed to evaluate the impact of sevoflurane during long-term sedation of critically ill patients on ‘weaning time’, efficiency, and patient’s safety compared to the standard intravenous sedation concept employing propofol.
Inhalative sedation; Intravenous sedation; Intensive care; Sevoflurane