The Effect of Ketamine Versus Etomidate for Rapid Sequence Intubation on Maximum Sequential Organ Failure Assessment Score: A Randomized Clinical Trial.

BACKGROUND: The use of induction agents for rapid sequence intubation (RSI) has been associated with hypotension in critically ill patients. Choice of induction agent may be important and the most commonly used agents are etomidate and ketamine. OBJECTIVE: This study aimed to compare the effects of a single dose of ketamine vs. etomidate for RSI on maximum Sequential Organ Failure Assessment (SOFA) score and incidence of hypotension. METHODS: This single-center, randomized, parallel-group trial compared the use of ketamine and etomidate for RSI in critically ill adult patients in the emergency department. The study was performed under Exception from Informed Consent. The primary outcome was the maximum SOFA score within 3 days of hospitalization. RESULTS: A total of 143 patients were enrolled in the trial, 70 in the ketamine group and 73 in the etomidate group. Maximum median SOFA score for the ketamine group was 6.5 (interquartile range [IQR] 5-9) vs. 7 (IQR 5-9) for etomidate with no significant difference (-0.2; 95% CI -1.4 to 1.1; p = 0.79). The incidence of post-intubation hypotension was 28% in the ketamine group vs. 26% in the etomidate group (difference 2%; 95% CI -13% to 17%). There were no significant differences in intensive care unit outcomes. Thirty-day mortality rate for the ketamine group was 11% (8 deaths) and for the etomidate group was 21% (15 deaths), which was not statistically different. CONCLUSIONS: There were no significant differences in maximum SOFA score or post-intubation hypotension between critically ill adults receiving ketamine vs. etomidate for RSI.

Effectiveness of the advisory display SmartPilot® view in the assessment of anesthetic depth in low risk gynecological surgery patients: a randomized controlled trial.

BACKGROUND: Assessment of appropriate anesthetic depth is crucial to prevent harm to patients. Unnecessary deep anesthesia can be harmful, potentially causing acute renal failure, myocardial injury, delirium, and an increased mortality rate. Conversely, too light anesthesia combined with muscle relaxants can result in intraoperative patient awareness and lead to serious psychological trauma. This trial aimed to ascertain the effectiveness of the advisory display SmartPilot® View (SPV), as a supplemental measure in the assessment of anesthetic depth in low risk gynecological surgery patients. The hypothesis was that the use of the SPV would increase the precision of assessment, and result in a higher mean arterial pressure. METHODS: This trial used a randomized, controlled, single-blind design with a homogeneous sample. Patients undergoing minor, low risk gynecological surgery were randomly assigned to two groups: a test group wherein current standards were supplemented with the advisory display SPV and a control group assessed using only the current standards. Female patients aged between 18 and 75 years with American Society of Anesthesiologists Physical Status Classification System scores of 1-3 undergoing planned general anesthesia using the total intravenous anesthetic method, combining propofol and remifentanil, were included. The exclusion criteria included a body mass index ≥ 35 kg/m2, a history of alcoholism, drug intake affecting propofol and remifentanil dynamics, and inability to consent. The independent sample t-test and chi-square test or Fisher's exact test were used to assess the statistical significance of differences between the two groups. RESULTS: A total of 114 patients were included in the analysis (test group n = 58, control group n = 56). No significant differences in the mean arterial pressure, heart rate, bispectral index, extubation delay, or post-anesthesia care unit stay were found between groups. CONCLUSIONS: The addition of the advisory display SmartPilot® View to current standards in the evaluation of anesthetic depth had no significant effect on the outcome. TRIAL REGISTRATION: The trial was registered on January 16th 2019 with ClinicalTrials.gov (ref: NCT03807271 ).

Medical, Political, and Economic Considerations for the Use of MAC for Endoscopic Sedation: Big Price, Little Justification?

The last few decades of gastrointestinal (GI) endoscopy have seen phenomenal growth. In many aspects, GI endoscopy has led the field of nonsurgical interventional medicine. In many aspects, this growth is facilitated by advancements in sedation-both drugs and techniques. Unfortunately, the topic of GI endoscopy sedation is also mired in many controversies, mainly emanating from the cost of anesthesia providers. While no one debates their role in the majority of advanced endoscopic procedures, the practice of universal propofol sedation in the USA, delivered by anesthesia providers, needs a closer look. In this review, medical, political, and economic considerations of this important topic are discussed in a very frank and honest way. While such ubiquitous propofol use has increased satisfaction of both patients and gastroenterologists, there is little justification. More importantly, going by the evidence, there is even less justification for the mandated anesthesia providers use for such delivery. Unfortunately, the FDA could not be convinced otherwise. The new drug fospropofol met the same fate. Approval of SEDASYS®, the first computer-assisted personalized sedation system, was a step in the right direction, nevertheless an insufficient step that failed to takeoff. As a result, in spite of years of research and efforts of many august societies, the logjam of balancing cost and justification of propofol sedation has continued. We hope that recent approval of remimazolam, a novel benzodiazepine, and potential approval of oliceridine, a novel short-acting opioid, might be able to contain the cost without compromising the quality of sedation.

Effect-Site Target-Controlled Infusion in the Obese: Model Derivation and Performance Assessment.

BACKGROUND: The aim of this study is to derive a propofol pharmacokinetic (PK) pharmacodynamic (PD) model to perform effect-site target-controlled infusion (TCI) in obese patients, and to analyze its performance along with that of other available PK models. METHODS: In the first step of the study, a 3-compartment PK model linked to a sigmoidal inhibitory Emax PD model by a first-order rate constant (keo) was used to fit propofol concentration-bispectral index (BIS) data. Population modeling analysis was performed by nonlinear mixed effects regression in NONMEM (ICON, Dublin, Ireland). PK data from 3 previous studies in obese adult patients (n = 47), including PD (BIS) data from 1 of these studies (n = 20), were pooled and simultaneously analyzed. A decrease in NONMEM objective function (ΔOBJ) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. In the second step of the study, we analyzed the predictive performance (median predictive errors [MDPE] and median absolute predictive errors [MDAPE]) of the current model and of other available models using an independent data set (n = 14). RESULTS: Step 1: The selected PKPD model produced an adequate fit of the data. Total body weight resulted in the best size scalar for volumes and clearances (ΔOBJ, -18.173). Empirical allometric total body weight relationships did not improve model fit (ΔOBJ, 0.309). A lag time parameter for BIS response improved the fit (ΔOBJ, 89.593). No effect of age or gender was observed. Step 2: Current model MDPE and MDAPE were 11.5% (3.7-25.0) and 26.8% (20.7-32.6) in the PK part and 0.4% (-10.39 to 3.85) and 11.9% (20.7-32.6) in the PD part. The PK model developed by Eleveld et al resulted in the lowest PK predictive errors (MDPE = <10% and MDAPE = <25%). CONCLUSIONS: We derived and validated a propofol PKPD model to perform effect-site TCI in obese patients. This model, derived exclusively from obese patient's data, is not recommended for TCI in lean patients because it carries the risk of underdosing.

Cardiovascular effects, induction and recovery characteristics and alfaxalone dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous anaesthesia in dogs.

OBJECTIVE: To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs. STUDY DESIGN: Prospective, blinded, randomized, experimental study. ANIMALS: A group of 12 intact female dogs. METHODS: Following intramuscular dexmedetomidine (10 µg kg-1) and methadone (0.1 mg kg-1) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg-1) (group AP) or alfaxalone (2 mg kg-1) preceded by fentanyl (2 µg kg-1) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg-1 minute-1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 µg kg-1 hour-1) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05). RESULTS: The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg-1 minute-1 (group AP) versus 0.13 ± 0.01 mg kg-1 minute-1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor.

Adverse Events and Resource Utilization After Spinal and General Anesthesia in Infants Undergoing Pyloromyotomy.

BACKGROUND AND OBJECTIVES: Interest in spinal anesthesia (SA) is increasing because of concern about the long-term effects of intravenous (IV) and inhaled anesthetics in young children. This study compared SA versus general anesthesia (GA) in infants undergoing pyloromyotomy. METHODS: Between 2000 to 2013, the University of Vermont Medical Center almost exclusively used SA for infant pyloromyotomy surgery, whereas Columbia University Medical Center relied on GA. Outcomes included adverse events (AEs) within 48 hours of surgery, operating room (OR) time, and postoperative length of stay (LOS). Regression was used to evaluate the association between anesthesia technique and outcomes, accounting for demographic and clinical covariates. RESULTS: We studied 218 infants with SA at the University of Vermont Medical Center and 206 infants with GA at Columbia University Medical Center. In the SA group, 96.3% of infants had adequate initial analgesic levels, but 35.8% required supplemental IV or inhaled anesthetic agents. Compared with GA, the risk of AEs in SA (adjusted odds ratio, 0.60; 95% confidence interval [CI], 0.27-1.36) did not significantly differ, but SA was associated with shorter OR times (17.5 minutes faster; 95% CI, 13.5-21.4 minutes) and shorter postoperative LOS (GA is 1.19 times longer; 95% CI, 1.01-1.40). CONCLUSIONS: Infants undergoing pyloromyotomy with SA had shorter OR times and postoperative LOS, no significant differences in AE rates, and decreased exposure to IV and inhaled anesthetics, although SA infants often still required supplemental anesthetics. Whether these differences result in any long-term benefit is unclear; further studies are needed to determine the risk of rare AEs, such as aspiration.

Prediction of postoperative pain from assessment of pain induced by venous cannulation and propofol infusion.

BACKGROUND: Postoperative pain may lead to delayed mobilization, persisting pain, and psychosocial distress. There are no simple and reliable techniques for prediction of postoperative pain. This study was designed to evaluate if pain induced by venous cannulation or propofol injection can be used to predict postoperative pain. METHODS: This prospective study included 180 patients scheduled for laparoscopic cholecystectomy. Pain intensity associated with peripheral venous cannulation and administration of propofol preoperatively and pain intensity, and use of opioid postoperatively was recorded. RESULTS: Patients scoring cannulation-induced pain intensity > 2.0 VAS units were given postoperative opioid more often (65% vs. 36%; P < 0.001), earlier (12 min vs. 90 min; P < 0.001), and in higher doses (4.8 mg vs. 0 mg; P < 0.001), and also reported higher levels of postoperative pain intensity (5.8 vs. 2.9 VAS units; P < 0.001). There were also significant (P < 0.01) correlations with postoperative pain intensity (rs = 0.24), time to opioid administration (rs = -0.26), and total dose of opioid (rs = 0.25). Propofol-induced pain intensity correlated significantly (P < 0.05) with postoperative pain intensity (rs = 0.19). CONCLUSION: Pain intensity associated with venous cannulation and propofol infusion can easily be evaluated at bedside before surgery without specific equipment or training. Patients scoring > 2.0 VAS units on venous cannulation were found to have 3.4 times higher risk of postoperative pain after laparoscopic cholecystectomy. Low pain intensity associated with venous cannulation and propofol infusion indicate lower risk of postoperative pain.

Is the anesthesiologist necessary in the endoscopy suite? A review of patients, payers and safety.

The use of propofol for sedation during endoscopy has been increasing, particularly given its association with superior patient satisfaction. Propofol sedation may also allow for higher quality endoscopy exams, increased efficiency of endoscopy suites and most particularly, permit better patient compliance with colonoscopy for colorectal cancer screening. However, propofol is typically provided by anesthesia specialists via monitored anesthesia care, and is associated with significant economic burden. Given the increasing use of monitored anesthesia care, which adds significant costs to endoscopy, payers are likely to react with changes in payer policies. One alternative to monitored anesthesia care is non-anesthesiologist administered propofol, which due to safety concerns and a lack of reimbursement has not been widely adopted in the US.

Comparison of Propofol, Etomidate, and Thiopental in Anesthesia for Electroconvulsive Therapy: A Randomized, Double-blind Clinical Trial.

OBJECTIVES: This study aimed to compare the effects of propofol, thiopental, and etomidate, which are routinely used in anesthesia for electroconvulsive therapy (ECT), on the cardiovascular system, seizure variables, recovery, cognitive functions, and response to treatment. METHODS: Male patients hospitalized at the Seventh Psychiatry Clinics of the Bakirköy Teaching Hospital for Psychiatry, Neurology, and Neurosurgery who were treated with ECT were investigated prospectively. The effects on cardiovascular system parameters (heart rate, blood pressure, and blood oxygenation), seizure variables (duration and intensity of seizure), and recovery variables were recorded at every session, on prespecified time points, and the findings of the first session were used in this evaluation. In addition, clinical responses to treatment were evaluated with tests of cognitive functions before and after a course of ECT. Adverse effects were recorded. RESULTS: The sociodemographic characteristics of the 3 treatment groups were similar. There were no significant differences among the groups in terms of effects on cardiovascular system variables, seizure variables, and cognitive functions. The clinical response to ECT was good in all groups, without any significant differences. CONCLUSIONS: Propofol, etomidate, and thiopental are associated with similar safety and efficacy profiles.

Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study.

INTRODUCTION: Midazolam and propofol used alone for long-term sedation are associated with adverse effects. Sequential use may reduce the adverse effects, and lead to faster recovery, earlier extubation and lower costs. This study evaluates the effects, safety, and cost of midazolam, propofol, and their sequential use for long-term sedation in critically ill mechanically ventilated patients. METHODS: A total of 135 patients who required mechanical ventilation for >3 days were randomly assigned to receive midazolam (group M), propofol (group P), or sequential use of both (group M-P). In group M-P, midazolam was switched to propofol until the patients passed the spontaneous breathing trial (SBT) safety screen. The primary endpoints included recovery time, extubation time and mechanical ventilation time. The secondary endpoints were pharmaceutical cost, total cost of ICU stay, and recollection to mechanical ventilation-related events. RESULTS: The incidence of agitation following cessation of sedation in group M-P was lower than group M (19.4% versus 48.7%, P = 0.01). The mean percentage of adequate sedation and duration of sedation were similar in the three groups. The recovery time, extubation time and mechanical ventilation time of group M were 58.0 (interquartile range (IQR), 39.0) hours, 45.0 (IQR, 24.5) hours, and 192.0 (IQR, 124.0) hours, respectively; these were significantly longer than the other groups, while they were similar between the other two groups. In the treatment-received analysis, ICU duration was longer in group M than group M-P (P = 0.016). Using an intention-to-treat analysis and a treatment-received analysis, respectively, the pharmaceutical cost of group M-P was lower than group P (P <0.01) and its ICU cost was lower than group M (P <0.01; P = 0.015). The proportion of group M-P with unbearable memory of the uncomfortable events was lower than in group M (11.7% versus 25.0%, P <0.01), while the proportion with no memory was similar (P >0.05). The incidence of hypotension in group M-P was lower than group (P = 0.01). CONCLUSION: Sequential use of midazolam and propofol was a safe and effective sedation protocol, with higher clinical effectiveness and better cost-benefit ratio than midazolam or propofol used alone, for long-term sedation of critically ill mechanically ventilated patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN01173443. Registered 25 February 2014.

The safety of propofol sedation for elective nonintubated esophagogastroduodenoscopy in pediatric patients.

OBJECTIVES: To evaluate the safety of deep sedation provided by pediatric intensivists for elective nonintubated esophagogastroduodenoscopy. DESIGN: Retrospective observational study. SETTING: The sedation program at the Helen DeVos Children's Hospital. PATIENTS: A 4-year retrospective analysis was done on all outpatient elective pediatric esophagogastroduodenoscopy procedures performed in an intensivist run sedation program. Safety was examined by reviewing the occurrence of minor and major adverse effects during esophagogastroduodenoscopy sedation. Interventions were studied and reported. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, 12,447 sedations were performed by the pediatric sedation program for various procedures. Two thousand one hundred forty-seven patients received 2,325 sedations (18.6%) for esophagogastroduodenoscopies performed for various indications. During the same time period, 53 (one for every 40 esophagogastroduodenoscopy sedations) were screened, found unsuitable for nonintubated sedation, and referred for general anesthesia. There were 2,254 sedations with propofol, 65 methohexital, five ketamine, and one fentanyl/midazolam sedation. Propofol sedation proved safe with a 2.1% prevalence of minor adverse events and no major events. Methohexital, on the other hand, had higher rate (p < 0.001) of minor events and one patient developed an anaphylactic reaction to its use. Regression analysis showed that other sedative agents were 8.6 times more likely to be associated with complications than propofol (odds ratio, 8.6; 95% CI, 4.1-18.2; p < 0.001). CONCLUSIONS: This study demonstrates that deep sedation for elective esophagogastroduodenoscopies can be provided safely in the appropriately screened patient by nonanesthesiologist physicians in a sedation program. These data suggest that propofol is a safe and effective agent for esophagogastroduodenoscopy sedation.

Propofol use in endoscopic retrograde cholangiopancreatography and endoscopic ultrasound.

Compared to standard endoscopy, endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are often lengthier and more complex, thus requiring higher doses of sedatives for patient comfort and compliance. The aim of this review is to provide the reader with information regarding the use, safety profile, and merits of propofol for sedation in advanced endoscopic procedures like ERCP and EUS, based on the current literature.

Septoplasty: under general or sedation anesthesia. Which is more efficacious?

The objective of the study was to assess the more efficacious anesthesia method in septal surgery. The prospective study was conducted at an academic secondary referral center. A prospective chart review of 60 patients, between the ages of 16 and 65, who underwent septal surgery under general (GA) or sedation (SDA) anesthesia during 1-year period was done. Mean age of the patients was 44.30 ± 13.29. Patients were divided into two groups according to the anesthesia method: general (group 1) or sedation (group 2). Intraoperative hemodynamic variables, surgery time, intraoperative blood loss volume, length of hospital stay, postoperative vomiting and nausea, postoperative pain score according to the visual analog scale (VAS) and cost analysis of each method were compared. Thirty-six males and 24 females with a mean age 44.30 ± 13.29 were included to the study. Total operation time, operation time, intraoperative and postoperative bleeding volume, postoperative nausea and vomiting, duration of hospital stay after surgery, were better in group 2. Postoperative pain scores and patient satisfaction about surgery were not statistically different. Cost of anesthesia in group 1 per patient was $44.35 ± 10.81 and in group 2, $16.29 ± 11.88 (p < 0.01). Hospital stay after surgery was much longer in group 1 than group 2 (p < 0.01). Using SDA is better in many ways including cost-effectiveness than using GA for septoplasty operation.

Risk assessment of postoperative nausea and vomiting in the intravenous patient-controlled analgesia environment: predictive values of the Apfel's simplified risk score for identification of high-risk patients.

PURPOSE: Opioid-based intravenous patient-controlled analgesia (IV PCA) is popular method of postoperative pain control, but many patients suffer from IV PCA-related postoperative nausea and vomiting (PONV). In this retrospective observational study, we have determined independent predictors of IV PCA-related PONV and predictive values of the Apfel's simplified risk score in pursuance of identifying high-risk patients. MATERIALS AND METHODS: We analyzed 7000 patients who received IV PCA with background infusion after elective surgery. Patients who maintained IV PCA for a postoperative period of 48 hr (completion group, n=6128) were compared with those who have discontinued IV PCA within 48 hr of surgery due to intractable PONV (cessation group, n=872). Patients, anesthetics, and surgical factors known for predicting PONV were evaluated by logistic regression analysis to identify independent predictors of IV PCA related intractable PONV. RESULTS: In a stepwise multivariate analysis, weight, background infusion dose of fentanyl, addition of ketolorac to PCA, duration of anesthesia, general anesthesia, head and neck surgery, and Apfel's simplified risk score were revealed as independent risk factors for intractable PONV followed by the cessation of IV PCA. In addition, Apfel's simplified risk score, which demonstrated the highest odds ratio among the predictors, was strongly correlated with the cessation rate of IV PCA. CONCLUSION: Multimodal prophylactic antiemetic strategies and dose reduction of opioids may be considered as strategies for the prevention of PONV with the use of IV PCA, especially in patients with high Apfel's simplified risk scores.

Comparison between the recovery time of alfentanil and fentanyl in balanced propofol sedation for gastrointestinal and colonoscopy: a prospective, randomized study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).

Efficiency and safety of inhalative sedation with sevoflurane in comparison to an intravenous sedation concept with propofol in intensive care patients: study protocol for a randomized controlled trial.

BACKGROUND: 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. METHOD/DESIGN: 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. DISCUSSION: This clinical study is designed to evaluate the impact of sevoflurane during long-term sedation of critically ill patients on 'weaning time', efficiency, and patient's safety compared to the standard intravenous sedation concept employing propofol. TRIAL REGISTRATION: EudraCT2007-006087-30; ISRCTN90609144.

[Perioperative medication management]. / Perioperatives Medikamentenmanagement.

The management of chronic medication in the perioperative phase represents as a serious challenge for the involved physicians. Especially patients with elevated ASA-scores frequently suffer from multiple co-morbidities which often need numerous medications. The probability of pharmacological interactions rises with the number of these medications. Moreover it must be taken into consideration that chronic medication potentially interferes with both intravenous and inhaled anesthetics and moreover, bleeding complications are more likely to occur in patients undergoing chronic pharmacotherapy. The aim of this article is to provide a summary of the existing evidence concerning perioperative medication in patients undergoing non-cardiac surgery. Several guidelines and advisories dealing with cardiovascular medication have been published during the last decade. The main scope of these publications was on beta-blockers and other cardiovascular medication. There is less evidence on not-cardiovascular medication as in most cases only case reports and expert opinions are published. Existing epidemiologic studies on this topic are rather heterogeneous.

Assessment of the relative potency of fentanyl buccal tablet to intravenous morphine in healthy volunteers using a thermally induced hyperalgesia pain model.

This exploratory randomized, double-blind, placebo-controlled, 5-treatment, 5-period crossover study was conducted using a thermally induced hyperalgesia pain model in 51 healthy volunteers (33 evaluable) to characterize the relative potency of fentanyl buccal tablet (FBT) versus intravenous morphine. Relative potency was assessed using the sum of pain intensity differences over 60 minutes after the application of a 43°C, 46°C, and 49°C painful stimulus following thermally induced hyperalgesia. Relative potency was also assessed by pupil diameter and responses to subjective questionnaires. The relative potency of FBT was 46.2 times that of intravenous morphine (95% confidence interval [CI], 17.6-575.3) based on the 49°C stimulus. The relative potency of FBT based on opiate-induced miosis was 44.6 (95% CI, 29.7-77.0) at 60 minutes. These results are an initial relative potency assessment and should not be considered guidance for dose-equivalent switching between agents in clinical practice.