Modified Observer's Assessment Of Alertness/Sedation Research Articles

Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects

BackgroundCyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers. MethodsFive cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg−1 min−1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring. ResultsNo serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift. ConclusionsInfusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern. Clinical trial registrationNTR4735.

Optimal effective-site concentration of remifentanil for sedation during plate removal of maxilla.

BackgroundRemoval of the plate following Le Fort I osteotomy and BSSO (bilateral sagittal split osteotomy) is a common procedure. However, patients who undergo plate removal experience intense pain and discomfort. This study investigated the half-maximal effective concentration (Ce50) of remifentanil in the prevention of plate removal pain under sedation using dexmedetomidine.MethodsThe study evaluated 18 patients, between 18 and 35 years of age, scheduled for elective surgery. Remifentanil infusion was initiated after sedation using dexmedetomidine, and started at a dose of 1.5 ng/mL on the first patient via target-controlled infusion (TCI). Patients received a loading dose of 1.0 µg/kg dexmedetomidine over 10 min, followed by a maintenance dose of 0.7 µg/kg/h. When the surgeon removed the plate, the patient Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score was observed.ResultsThe Ce of remifentanil ranged from 0.9 to 2.1 ng/mL for the patients evaluated. The estimated effect-site concentrations of remifentanil associated with a 50% and 95% probability of reaching MOAA/S score of 3 were 1.28 and 2.51 ng/mL, respectively.ConclusionsPlate removal of maxilla can be successfully performed without any pain or adverse effects by using the optimal remifentanil effect-site concentration (Ce50, 1.28 ng/mL; Ce95, 2.51 ng/mL) combined with sedation using dexmedetomidine.

A prediction model for hypoxemia during routine sedation for gastrointestinal endoscopy

OBJECTIVES:The current study was designed to assess the clinical predictors of hypoxemia and to develop a multivariable, predictive model for hypoxemia during routine gastrointestinal endoscopy.METHODS:In total, 308 patients were enrolled in the analysis. Demographic data, concurrent chronic disease information, anesthetic dose and Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores were collected and analyzed statistically.RESULTS:Multivariate logistic regression indicated that age (OR: 1.04; 95%CI 1.01-1.08), body mass index (BMI) (OR: 1.12; 95%CI: 1.02-1.21) and habitual snoring (OR: 3.71; 95%CI: 1.62-8.48) were independently associated with hypoxemia. A logistic regression function (LR model) was developed to predict hypoxemia considering the parameters of -7.73+0.04 age (years), +0.11 BMI, and +1.31 habitual snoring (yes or no). The area under the receiver operating characteristic (ROC) curve for the LR model was 0.76.CONCLUSIONS:The LR model, consisting of age, BMI and habitual snoring, was a useful predictor of hypoxemia during routine sedation for gastrointestinal endoscopy.

Dexmedetomidine pharmacokinetic–pharmacodynamic modelling in healthy volunteers: 1. Influence of arousal on bispectral index and sedation

BackgroundDexmedetomidine, a selective α2-adrenoreceptor agonist, has unique characteristics, such as maintained respiratory drive and production of arousable sedation. We describe development of a pharmacokinetic–pharmacodynamic model of the sedative properties of dexmedetomidine, taking into account the effect of stimulation on its sedative properties. MethodsIn a two-period, randomized study in 18 healthy volunteers, dexmedetomidine was delivered in a step-up fashion by means of target-controlled infusion using the Dyck model. Volunteers were randomized to a session without background noise and a session with pre-recorded looped operating room background noise. Exploratory pharmacokinetic–pharmacodynamic modelling and covariate analysis were conducted in NONMEM using bispectral index (BIS) monitoring of processed EEG. ResultsWe found that both stimulation at the time of Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale scoring and the presence or absence of ambient noise had an effect on the sedative properties of dexmedetomidine. The stimuli associated with MOAA/S scoring increased the BIS of sedated volunteers because of a transient 170% increase in the effect-site concentration necessary to reach half of the maximal effect. In contrast, volunteers deprived of ambient noise were more resistant to dexmedetomidine and required, on average, 32% higher effect-site concentrations for the same effect as subjects who were exposed to background operating room noise. ConclusionsThe new pharmacokinetic–pharmacodynamic models might be used for effect-site rather than plasma concentration target-controlled infusion for dexmedetomidine in clinical practice, thereby allowing tighter control over the desired level of sedation. Clinical trial registrationNCT01879865.

Continued midazolam versus diphenhydramine in difficult-to-sedate patients: a randomized double-blind trial

Current guidelines recommend diphenhydramine in patients undergoing endoscopy who are not adequately sedated with a benzodiazepine and opioid combination. Because this practice has not been adequately assessed, we performed a randomized, double-blind trial comparing diphenhydramine with continued midazolam in such patients. Patients undergoing elective colonoscopy with moderate sedation were eligible. Sedation was measured with the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score with adequate sedation defined as 3 on a 0- to 5-point scale. Patients not adequately sedated with midazolam 5 mg and fentanyl 100 μg were randomly assigned to diphenhydramine 25 mg versus continued midazolam 1.5 mg. Adequacy of sedation was assessed 3 minutes after each study medication dose. If MOAA/S was 4 to 5, study medication was repeated, to a maximum of 3 doses. The primary endpoint was adequate sedation. The planned enrollment of 200 patients (100 in each study group) was attained. Adequate sedation wasachieved less often with diphenhydramine than midazolam (27% vs 65%, difference= -38%; 95% CI, -50% to -24%; P< .0001). After study medications were completed, more patients required additional medication for sedation or analgesia with diphenhydramine versus midazolam (84% vs 68%, P= .008), whereas the time to discharge from the recovery unit was similar (134 vs 129 minutes). Treatment effect was consistent across subgroups including age≤55, substance abuse, benzodiazepine use, opioid use, and psychiatric medication use. Endoscopists performing moderate sedation should continue midazolam rather than switching to diphenhydramine in patients who do not achieve adequate sedation with usual doses of midazolam and an opioid. (Clinical trial registration number: NCT01769586.).

Patient satisfaction after endoscopic submucosal dissection under propofol-based sedation: a small premedication makes all the difference.

Ideal sedation for endoscopic submucosal dissection (ESD) aims to satisfy both the endoscopist and patient. However, previous studies show that a satisfactory procedure for the endoscopist does not equal higher patient satisfaction. This study attempted to find a sedation protocol that is able to increase patient satisfaction during propofol-based sedation by adding low-dose midazolam as premedication. Seventy-two adult patients were randomly allocated to receive either 0.02mg/kg midazolam (Midazolam Group) or placebo (Control Group) as premedication before ESD. Sedation was done by targeting Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale of 3 or 4 with continuous propofol infusion and bolus doses of fentanyl. Satisfaction scores of the endoscopists and patients, and whether the patient was willing to receive the same sedation method in the future was assessed. Interim analysis was done after enrollment of 50% of patients. This study was prematurely terminated when interim analysis showed that patients willing to receive the same sedation method in the future were significantly lower in the Control Group compared to the Midazolam Group (P=0.001). There was no difference in sedation time, procedure and recovery time, drug requirements and adverse events between the two groups. Endoscopist and overall patient satisfaction scores, patient pain scores and degree of recall were also similar between groups. A small dose of midazolam given as premedication before propofol-based sedation is able to reduce patient reluctance to repeat the same procedure in the future, without affecting procedural performance, recovery time or endoscopist satisfaction.

A comparison of sedation protocols for gastric endoscopic submucosal dissection: moderate sedation with analgesic supplementation vs analgesia targeted light sedation

Moderate to deep sedation has been recommended during endoscopic submucosal dissection (ESD). However, it is often accompanied by adverse events such as respiratory depression or aspiration pneumonia. This study investigated the respiratory complications and ESD outcomes of two sedation protocols: moderate sedation with analgesic supplementation (MSAS) and analgesia targeted light sedation (ATLS). The clinical data of 293 patients who underwent ESD between May and December 2012 were reviewed. During the first 4 months, 155 patients were managed by moderate sedation [Modified Observer Assessment of Alertness/Sedation (MOAA/S) at 2-3] with the MSAS protocol. During the latter period, 138 patients were managed using the ATLS protocol (MOAA/S at 4-5). For both protocols, propofol and remifentanil were infused for sedation and pain control, respectively. The ATLS protocol required less propofol [22.9 (sd 17.3) vs 88.1 (44.0) µg kg(-1) min(-1), P<0.001] and more remifentanil [6.8 (sd 3.1) vs 4.9 (3.0) µg kg(-1) hr(-1), P<0.001] than the MSAS protocol. The desaturation events during the procedure occurred significantly less often (2.2 vs 12.9%, P=0.001) and recovery was significantly faster [19.7 (sd 4.8) vs 27.9 (16.0) min, P<0.001] with the ATLS protocol than with the MSAS protocol. The incidence of aspiration pneumonia with the ATLS protocol was 1.4% compared with 5.2% with the MSAS protocol (P=0.109). There were no differences in outcomes and complications of ESD. The ATLS protocol reduced the incidence of desaturation events without affecting ESD performance compared with the MSAS protocol. There was also a trend towards a low incidence of aspiration pneumonia with the ATLS protocol.

Optimal Dose of Prophylactic Dexmedetomidine for Preventing Postoperative Shivering

Objective The aim of this study was to investigate the optimum dosage of dexmedetomidine for prevention of postanesthetic shivering.Methods One-hundred thirty two ASA physical status I-II patients scheduled for elective laparoscopic total hysterectomy were enrolled in this randomised, placebo-controlled study. Patients were randomly allocated to receive dexmedetomidine in four groups: group S (0.9% normal saline), group D0.5 (dexmedetomidine 0.5 µg/kg), group D0.75 (dexmedetomidine 0.75 µg/kg), group D1.0 (dexmedetomidine 1.0 µg/kg). Time to extubation and tympanic temperature during and after operation were measured. Shivering was graded (0-3 scale) upon patients arrival to the PACU and every ten minutes thereafter up to forty minutes. Sedation and first rescue analgesic time at the PACU were evaluated.Results The incidence of shivering was significantly lower in group D0.75 and D1.0 than in group S (P < 0.05). There were significantly fewer patients with a shivering score of 2 or 3 in groups D0.75 and D1.0 than in group S (P < 0.05, P < 0.001). Extubation time was shorter in group S than in groups D0.75 and D1.0 (P < 0.05). Tympanic temperature at 40 minutes postoperatively in the recovery room was higher in group S than in the other dexmedetomidine groups (P < 0.05)Fewer patients required rescue analgesia in groups D0.75 and D1.0 than in group S (P < 0.001), and the time to rescue analgesia was longer in group D1.0 than in group S (P < 0.001). Modified Observer's Assessment of Alertness/Sedation (MOAA/S) at arrival in the PACU was lower in all dexmedetomidine groups than in group S (P < 0.05).Conclusions Our results suggest that dexmedetomidine 0.75 or 1.0 µg/kg provides effective prophylaxis against postoperative shivering as well as an analgesic effect. Though potential for intraoperative requirement for atropine, sedation in the immediate recovery period and delayed extubation time with dexmedetomidine was noted, there were no major clinical impacts on the overall recovery from anesthesia.

Bispectral index monitoring as an adjunct to nurse-administered combined sedation during endoscopic retrograde cholangiopancreatography

To determine whether bispectral index (BIS) monitoring is useful for propofol administration for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP). 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. 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. 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.

Safety evaluation of fospropofol for sedation during minor surgical procedures

Study Objective To evaluate the safety of intravenous (IV) fospropofol when used to provide minimal to moderate sedation in patients undergoing minor surgical procedures. Design Phase 3, open-label, single-arm study. Setting Multi-center. Patients 123 ASA physical status I, II, III, and IV patients, aged ≥18 years. Interventions Patients were pretreated with fentanyl 50 μg before receiving an initial dose of IV fospropofol 6.5 mg/kg. Patients could receive up to 5 supplemental doses of fospropofol 1.63 mg/kg to reach a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score ≤ 4 to allow the start of the procedure and to maintain adequate sedation levels during the procedure. Measurements Study endpoints included measures of sedation depth, requirement for supplemental sedative doses, use of alternative sedatives, and the frequency and nature of treatment-emergent and sedative-related adverse events. Main Results A mean of 2.4 supplemental doses of fospropofol was administered, and in 60% of patients, two or fewer supplemental doses of fospropofol were sufficient to initiate and complete the procedure. Alternative sedative medication was administered in 6 of 123 patients (4.9%). Mean (SD) MOAA/S score during the procedure was 3.8 (0.5). Sixty-one percent (61%) of patients had a MOAA/S score of 5 (fully alert) within two minutes after the end of the procedure. Few patients (7 of 123; 5.7%) had MOAA/S scores of 0 to 1 (deep sedation) during the procedure, and all 7 were either ASA physical status I (n = 1) or II (n = 6). The most common treatment-related adverse events (TRAEs) were self-limited: paresthesias (62.6%) and pruritus (27.6%). Five patients experienced sedation-related adverse events, including hypotension (n = 4), bradycardia (concurrently with hypotension and managed with atropine; n = 1), or hypoxemia (less than one min and managed with chin lift and verbal stimulation; n = 1). Twenty patients with previous or existing hepatic disease (ranging from minimal to severe) and 5 patients with severe renal impairment had adverse events similar to the overall population. No deaths were reported, and no patient discontinued the study due to adverse events. Conclusion An initial dose of IV fospropofol 6.5 mg/kg with supplemental doses was safe and well-tolerated as moderate sedation for use in minor surgical procedures.

Efficacy of bispectral index monitoring as an adjunct to propofol deep sedation for ERCP: a randomized controlled trial

We sought to determine whether bispectral index (BIS) monitoring is a useful adjunct to the administration of propofol titrated to deep sedation, as measured by reductions of doses of propofol administered during endoscopic retrograde cholangiopancreatography (ERCP). 90 consecutive patients undergoing ERCP were randomized to receive propofol titrated to deep sedation, with the BIS value either visible (BIS group, n = 46) or invisible (control group, n = 44) to the anesthesiologist. In the BIS group, the anesthesiologist was instructed to use the BIS value as the primary end point for titration of sedation, and to target BIS values between 40 and 60. For the control group, the anesthesiologist was instructed to titrate propofol according to routine practice in the unit using the modified Observer's Assessment of Alertness/Sedation (MOAA/S) Scale (MOAA/S score 0). The mean (SD) propofol doses (mg/min per kg weight) were 0.139 (0.02) and 0.193 (0.02) for the BIS and control groups, respectively (P < 0.001). Mean (SD) BIS values throughout the procedure were 61.68 (7.5) and 56.93 (4.77) for the BIS and control groups, respectively (P = 0.001). During the maintenance phase of sedation (MOAA/S score 0), the mean (SD) BIS values were 53.73 (8.67) and 45.65 (4.39) for the BIS and control groups, respectively (P < 0.001). Our data suggest that BIS monitoring led to a reduction in the mean propofol dose when the BIS value was used as the primary target for sedation in ERCP procedures.

A Computer-Assisted Personalized Sedation System to Administer Propofol Versus Standard-of-Care Sedation for Colonoscopy and Esophagogastroduodenoscopy: A 1,000-Subject Randomized, Controlled, Multicenter, Pivotal Trial

A Computer-Assisted Personalized Sedation System to Administer Propofol Versus Standard-of-Care Sedation for Colonoscopy and Esophagogastroduodenoscopy: A 1,000-Subject Randomized, Controlled, Multicenter, Pivotal Trial

Fospropofol Disodium Is Effective and Safe for Sedation during Colonoscopy

Purpose: Fospropofol disodium (FP), a water-soluble prodrug of propofol, possesses a pharmacokinetic profile characterized by a smooth and predictable rise in propofol plasma concentrations that is unique from its active metabolite, propofol. This double-blind, multicenter, phase 3 study evaluated the safety & efficacy of FP 6.5 mg/kg & 2 mg/kg in patients undergoing colonoscopy. Methods: 314 patients ≥18 years (ASA P1 to P3) were randomized to FP 6.5 mg/kg, FP 2 mg/kg, or midazolam (MD) 0.02 mg/kg in a 3:2:1 allocation following pretreatment with fentanyl 50 mcg. Patients were permitted to receive up to 3 supplemental doses of study drug before being considered a treatment failure & receiving an alternative sedative. Sedation was assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S). The primary endpoint was sedation success, defined by 3 consecutive MOAA/S scores of ≤4 after administration of sedative, and completion of the procedure without use of an alternative sedative medication & without manual/mechanical ventilation. Other endpoints included measures of clinical benefit, recovery, memory retention, patient & physician satisfaction, and safety. Results: Sedation success (87% vs 26%; P < .001) was higher and the requirement for supplemental analgesic medication lower (55% vs 77%; P= .001) in the FP 6.5 mg/kg group than the FP 2 mg/kg group. Patients in the 6.5 mg/kg group were less likely to remember being awake during the procedure (51% vs 100%; P < .0001). The majority of patients in both groups reported willingness to use the sedative again (96% vs 91%). Patients in the FP 6.5 mg/kg group had higher memory retention (67%) than patients in the FP 2 mg/kg group (59%). Mean physician satisfaction scores were higher is the FP 6.5 mg/kg group (7.7) than in the FP 2 mg/kg group (4.5), P < .001. FP was well tolerated, with no serious treatment-related adverse events (TRAEs), deaths, or AE-related procedure discontinuations. The most common TRAEs in the FP 6.5 mg/kg and 2 mg/kg groups were paresthesias (68% vs 60%) and pruritus (16% vs 26%). Six patients experienced transient sedation-related AEs: FP 6.5 mg/kg (hypoxemia [resolved following repeated verbal stimulation, N = 1], hypotension [N = 2]); FP 2 mg/kg (hypotension [N = 2]); midazolam (hypotension). Conclusion: The FP 6.5 mg/kg dosing regimen is safe and effective for sedation during colonoscopy and is associated with a high level of sedation success, patient and physician satisfaction, and clear-headed recovery.

Safety and Efficacy of Fospropofol Disodium Versus Midazolam Hydrochloride for Sedation in Elderly Patients Undergoing Colonoscopy

Purpose: This study assessed the efficacy and safety of fospropofol disodium (AQUAVAN® injection, AQ) compared with midazolam hydrochloride (MD) in elderly patients undergoing colonoscopy. Methods: This was a phase 2, multicenter, randomized (stratified by age and center), open-label study. Patients aged >65 years with ASA status l/ll/lll were randomized to receive an intravenous bolus of AQ (525, 595, or 735 mg) or MD (0.5, 0.75, or 1.0 mg); dosing was based on patient weight. All patients received pretreatment with fentanyl citrate (0.5 μg/kg). Supplemental dosing of AQ/MD and fentanyl were permitted for inadequate sedation and analgesia, respectively. The protocol and informed consent form were approved by a central Institutional Review Board. Sedation success was defined as 3 consecutive Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores ≤4 and completion of the procedure without the need for alternative sedatives or manual/mechanical ventilation. Summary statistics were provided for all endpoints. Results: Fifteen patients received AQ and 5 patients received MD. Mean age was 70 years (range, 65–76 years). All 15 patients in the AQ arm achieved sedation success, as defined under Methods, compared with 0 patients in the MD arm (P < 0.001). A single dose of study drug was sufficient to initiate and maintain sedation for 13/15 AQ-treated patients. AQ and MD were well tolerated. Hypoxia (AQ, 6/15; MD, 1/5) and paresthesias (AQ, 4/15; MD, 0/5) were the most frequently reported adverse events (AEs). Hypoxia was defined as SpO2 of <90% OR a 3% decrease from baseline. Sedation-related AEs were minimal and were managed without difficulty (3 resolved spontaneously and 3 resolved with increased oxygen flow). There were no serious AEs or deaths. No patients required manual ventilation or intubation. Efficacy results are summarized below. [figure1]TableConclusions: Although interpretation of results is limited by the sample size, AQ appears to be safe and effective for moderate sedation in elderly patients undergoing colonoscopy procedures.

AQUAVAN® for Moderate Sedation during Colonoscopy

Purpose: Fospropofol disodium (AQUAVAN® Injection, AQ) a prodrug of propofol, is being developed for use in procedures requiring minimal to moderate sedation. This randomized, double-blind, multicenter, phase 2, dose-response study was designed to assess the optimal dose of AQ during colonoscopy. Methods: Patients (ASA I–IV, age ≥18 years) were stratified by age and ASA status and randomly assigned to receive a bolus dose of either AQ (2.0, 5.0, 6.5, or 8.0 mg/kg) or midazolam (0.02 mg/kg) following pretreatment with fentanyl citrate (50 μg). Midazolam was included in this study as a safety reference. Patients were permitted to receive supplemental doses of sedative and analgesic. Efficacy endpoints included: sedation success, treatment success, sedation adequacy, safety, measures of clinical benefit, and recovery. Sedation success was defined as 3 consecutive Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores of ≤4 after administration of sedative medication, AND completion of the procedure without use of an alternative sedative medication, AND without requiring manual/mechanical ventilation. Treatment success was defined as completing the procedure without requiring alternative sedative medications AND without requiring manual/mechanical ventilation.TableResults: 127 patients were randomized and completed the study. Demographic and baseline characteristics were similar in all groups. [figure1] Burning sensation and paresthesia were the most common adverse events. Sedation-related adverse events were noted in 3.8% and 12.0% of patients in the AQ 5.0 and 6.5 mg/kg groups, respectively. No patient required manual/mechanical ventilation. No deaths or serious adverse events occurred. Conclusions: AQ was safe and effective for colonoscopy at a moderate level of sedation. An initial bolus of 6.5 mg/kg of AQ achieved the optimal combination of sedation and safety.

Deep Sedation Occurs Frequently During Elective Endoscopy with Meperidine and Midazolam

Although moderate (conscious) sedation is intended during elective gastrointestinal endoscopy, unintended levels of deep sedation occur. The aims of this study were to prospectively evaluate the incidence and risk factors of deep sedation during elective endoscopy with meperidine and midazolam intended to maintain a level of moderate sedation. Eighty American Society of Anesthesiology class 1-2, outpatients presenting for elective esophagogastroduodenoscopy (EGD), colonoscopy, endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasonography (EUS) were offered enrollment. Intravenous meperidine and midazolam were administered according to a standardized protocol. Hemodynamic parameters and levels of sedation were assessed and recorded by a single observer at 3-min intervals. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale (ranging 1-5) is a subjective sedation assessment scale used to assess sedation levels. Occurrence of deep sedation, defined by MOAA/S 1-2, was recorded. Univariable and multivariable analyses were used to assess predictors of deep sedation. Deep sedation occurred in 54/80 (68%) patients for a total of 204/785 (26%) of total sedation assessments. The percentage of deep sedation episodes of all sedation-level observations by procedure was 26% for EGD, 11% for colonoscopy, 35% for ERCP, and 29% for EUS. Deep sedation occurred at least once in 60% of EGD, 45% of colonoscopy, 85% of ERCP, and 80% of EUS. Multivariable analysis showed that only ERCP and EUS were independent risk factors of deep sedation. Deep sedation occurs frequently during elective endoscopy with meperidine and midazolam used with the intent of moderate sedation. ERCP and EUS are risk factors for the occurrence of deep sedation, independent of sedation dose or length of procedure.

Comparison of a New Bispectral Index (BIS) Algorithm to Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Scale in Moderate Sedation (MS)

Background: Assessment of sedation levels in endoscopy is crucial for patient safety. Sedation assessment is currently guided by indirect measures: vital signs, direct observation, and subjective sedation assessment like the MOAA/S scale. BIS monitoring is a mathematical evaluation of frontal cortex EEG activity used to improve general anesthetic titration and patient recovery. Current BIS algorithms do not differentiate various levels of MS. Aim: To compare the new BIS monitoring algorithm (BIS Revision 4.1) to MOAA/S scale for MS during elective endoscopy. Methods: 80 pts (43M/37F, mean age 61 yrs) were studied using a balanced cohort of procedures (20-EGD; 20-Colon; 20-ERCP; 20-EUS). IV MS (meperidine/midazolam) was administered. BIS levels and MOAA/S scores were recorded q 3 min. BIS level (0-100; 0=flatline EEG to 100=fully awake) and MOAA/S score (1-5; 1=unresponsive to shaking to 5=coherent). The mean BIS level and MOAA/S score were compared. Results: Levels of sedation achieved: 54 pts (67.5%) deep sedation and 26 pts (32.5%) mild to moderate sedation. The correlation coefficient between BIS level and MOAA/S score was 0.66 (p < 0.01; Graph). The new BIS algorithm had excellent correlation to mild/moderate sedation levels (MOAA/S 2-5; p < 0.001) but failed to discriminate between moderate/deep sedation levels (MOAA/S 1-2; p = 0.75). Conclusions: (1)Deep sedation occurs frequently during elective endoscopy. (2)The new BIS algorithm is successful in discriminating levels of mild/moderate sedation, but is no more effective than direct observation (MOAA/S score) at distinguishing between moderate/deep levels of sedation. Clinical implication: Since a large percentage of patients experience deep sedation during elective endoscopy, the new BIS algorithm needs to be refined to differentiate deeper levels of sedation.