A lack of evidence of superiority of propofol versus midazolam for sedation in mechanically ventilated critically ill patients: a qualitative and quantitative systematic review

Propofol and midazolam are often used for sedation in the intensive care unit. The aim of this systematic review was to estimate the efficacy and harm of propofol versus midazolam in mechanically ventilated patients. A systematic search (Medline, Cochrane Library, Embase, bibliographies), any language, up to June 1999 was performed for reports of randomized comparisons of propofol with midazolam. Data from 27 trials (1624 adults) were analyzed. The average duration of sedation varied between 4 and 339 h. In 10 trials, the duration of adequate sedation was longer with propofol (weighted mean difference 2.9 h; 95% confidence interval [CI], 0.2-5.6 h). In 13 trials (mostly postoperative), sedation lasted 4 to 35 h; in 9 of those, average weaning time from mechanical ventilation with propofol was 0.8-4.3 h; with midazolam it was 1.5-7.2 h (weighted mean difference 2.2 h [95% CI, 0.8 to 3.7 h]). In 8 trials, sedation lasted 54 to 339 h; there was a lack of evidence for difference in weaning times. Arterial hypotension (relative risk 2.5 [95% CI, 1.3 to 4.5]; number-needed-to-treat, 12), and hypertriglyceridemia (relative risk 12.1 [95%CI, 2.9 to 49.7]; number-needed-to-treat, 6) occurred more often with propofol. The duration of adequate sedation time is longer with propofol compared with midazolam. In postoperative patients with sedation <36 h, weaning is faster with propofol. Implications: The duration of adequate sedation time is longer with propofol compared with midazolam. In postoperative patients with sedation < 36 h, weaning is faster with propofol.     

不同剂量咪达唑仑与异丙酚催眠效应的相互作用

目的 评价不同剂量咪达唑仑与异丙酚催眠效应的相互作用.方法 择期全麻病人120例,ASA Ⅰ或Ⅱ级,年龄18～60岁,体重40～80 kg,随机分为4组(n=30),各组分别随机分为6个亚组,M组和P组各亚组分别静脉注射咪达唑仑0.04、0.06、0.08、0.10、0.12、0.15 mg/kg、异丙酚0.8、1.0、1.2、1.5、1.8、2.2 mg/kg;MP1组和MP2组各亚组分别按咪达唑仑与异丙酚ED50等效比1:13(咪达唑仑剂量分别为0.022、0.028、0.033、0.039、0.044、0.055 mg/kg)和临床常用比例1:10(咪达唑仑剂量分别为0.03、0.04、0.045、0.05、0.055、0.06 mg/kg)行麻醉诱导.M组、P组、MP1组和MP1组分别于注药后3、1,1、1 min时行警觉,镇静(OAA/S)评分,催眠有效标准:OAA/S评分≤2分.采用加权概率单位法计算半数有效剂量(ED50)及其95%可信区间(95%CI);采用等辐射分析法判断两药催眠效应的相互作用.结果 M组、MP1.2组咪达唑仑催眠效应的ED50及其95%CI分别为0.088(0.066～0.110)、0.031(0.026～0.036)、0.045(0.040～0.049)mg/kg;P组、MP1.2组异丙酚催眠效应的ED50及其95%CI为1.142(0.933～1.350)、0.421(0.343～0.480)、0.450(0.399～0.491)mg/kg.结论 麻醉诱导时咪达唑仑与异丙酚按ED50等效剂量比1:13给药,两药催眠效应为协同作用;按临床常用剂量比1:10给药时两药催眠效应为相加作用.     

Bispectral Index Monitoring during Sedation with Sevoflurane, Midazolam, and Propofol

Background : Bispectral Index (BIS) has been used to measure sedation depth. Ideally, to guide anesthetic management, range of BIS scores at different sedation levels should not overlap, and BIS should be independent of drug used. This study assessed ability of BIS to predict sedation depth between sevoflurane, propofol, and midazolam. Quality of recovery was also compared.

Methods : Patients undergoing surgery with local or regional anesthesia and sedation were randomized to sevoflurane (n = 23), midazolam (n = 21), or propofol (n = 22). Sedation was titrated to Observers's Assessment of Alertness-Sedation score of 3 (responds slowly to voice). BIS and Observers's Assessment of Alertness-Sedation were measured every 5 min. BIS prediction probability (PK) was compared between drugs. Recovery was assessed by BIS and Digit Symbol Substitution and memory tests.

Results : Bispectral Index of responders to voice was significantly different from nonresponders (86 +/- 10 vs. 74 +/- 14, mean +/- SD;P < 0.001) However, wide variability and overlap in BIS were observed (25th-75th percentile, responders vs. non-responders: 79-96 vs. 65-83). BIS of responders was different for sevoflurane versus propofol and midazolam. BIS was a better predictor of propofol sedation than sevoflurane or midazolam (PK = 0.87 +/- 0.11, 0.76 +/- 0.01, and 0.69 +/- 0.02, respectively;P < 0.05). At 10 min after the procedure, 76, 48, and 24% of sevoflurane, propofol, midazolam patients, respectively, returned to baseline Digit Symbol Substitution scores (P < 0.05). Excitement-disinhibition occurred in 70, 36, and 5% of sevoflurane, propofol, and midazolam patients, respectively (P < 0.05).     

Bispectral index monitoring during sedation with sevoflurane, midazolam, and propofol.

BACKGROUND: Bispectral Index (BIS) has been used to measure sedation depth. Ideally, to guide anesthetic management, range of BIS scores at different sedation levels should not overlap, and BIS should be independent of drug used. This study assessed ability of BIS to predict sedation depth between sevoflurane, propofol, and midazolam. Quality of recovery was also compared. METHODS: Patients undergoing surgery with local or regional anesthesia and sedation were randomized to sevoflurane (n = 23), midazolam (n = 21), or propofol (n = 22). Sedation was titrated to Observers's Assessment of Alertness-Sedation score of 3 (responds slowly to voice). BIS and Observers's Assessment of Alertness-Sedation were measured every 5 min. BIS prediction probability (PK) was compared between drugs. Recovery was assessed by BIS and Digit Symbol Substitution and memory tests. RESULTS: Bispectral Index of responders to voice was significantly different from nonresponders (86 +/- 10 vs. 74 +/- 14, mean +/- SD; P < 0.001) However, wide variability and overlap in BIS were observed (25th-75th percentile, responders vs. non-responders: 79-96 vs. 65-83). BIS of responders was different for sevoflurane versus propofol and midazolam. BIS was a better predictor of propofol sedation than sevoflurane or midazolam (PK = 0.87 +/- 0.11, 0.76 +/- 0.01, and 0.69 +/- 0.02, respectively; P < 0.05). At 10 min after the procedure, 76, 48, and 24% of sevoflurane, propofol, midazolam patients, respectively, returned to baseline Digit Symbol Substitution scores (P < 0.05). Excitement-disinhibition occurred in 70, 36, and 5% of sevoflurane, propofol, and midazolam patients, respectively (P < 0.05). CONCLUSION: Individual BIS scores demonstrate significant variability, making it difficult to predict sedation depth. The relation between BIS and sedation depth may not be independent of anesthetic agent. Quality of recovery was similar between drugs, but excitement occurred frequently with sevoflurane.     

Differential effects of clonidine and dexmedetomidine on gastric emptying and gastrointestinal transit in the rat

We have studied the effect of clonidine, dexmedetomidine and morphine on gastric emptying and gastrointestinal transit in the rat. In one group, each agonist was injected i.p. in 6-12 male Wistar rats. In another group of rats, yohimbine, naloxone or saline was injected with an agonist. At 30 min, radiolabelled saline 1 ml was infused into the stomach. At 1 h, gastric emptying and gastrointestinal transit were calculated by measuring the radioactivity in the gastrointestinal tract. We found that clonidine and dexmedetomidine strongly inhibited gastrointestinal transit (ED50 0.08 and 0.04 mg kg-1, respectively). They also significantly inhibited gastric emptying (P < 0.05), but the effect was weak (95% confidence intervals for difference from saline 8.2-34.9% with clonidine 1 mg kg-1 and 3.4-15.4% with dexmedetomidine 0.03 mg kg-1). Morphine strongly inhibited both gastric emptying and gastrointestinal transit (ED50 2.8 and 1.2 mg kg-1, respectively). Yohimbine significantly antagonized the inhibitory effects of clonidine and dexmedetomidine (P < 0.05), whereas naloxone, which significantly antagonized the effect of morphine (P < 0.01), did not antagonize the effect of either of the other agonists.      

Propofol sedation with fentanyl or midazolam during oesophagogastroduodenoscopy in children

BACKGROUND AND OBJECTIVE: Sedation is commonly used to facilitate diagnostic procedures in children. The aim of our study was to investigate sedation in children using propofol alone or combined with fentanyl or midazolam with regard to efficacy, adverse reactions or side-effects related to the drugs, ease of operation for the endoscopist, and time to discharge from the post-anaesthesia care unit. METHODS: We prospectively studied 240 children, aged 1-12 yr of age, undergoing endoscopic procedures of the upper gastrointestinal tract. The patients were given an oral premedication with midazolam (0.5 mg kg(-1)) and were then randomly allocated to one of the three study groups: propofol alone (Group P), propofol with fentanyl 1 mug kg-1 (Group PF) or propofol with midazolam 0.1 mg kg(-1) (Group PM). Additional doses of propofol given during the procedure were recorded. Adequacy of sedation and ease of procedure (easy, adequate, impossible) were evaluated by the endoscopist, who was blinded as to the drugs used. RESULTS: The duration of the procedure and the recovery period were similar in the three groups. The number of patients requiring supplemental doses of propofol to permit safe completion of gastroscopy was 31 in Group P (=39%; eight of these required two additional doses), 14 in Group PM (=18%), and 11 in Group PF (=13%) (P < 0.05). There was a lower incidence of adverse events in Group PM and in Group PF than in Group P (P < 0.05). CONCLUSIONS: Propofol in combination with fentanyl or midazolam gives better sedation and ease of endoscopy than propofol alone.     

Interactive effect of morphine and dexmedetomidine on gastric emptying and gastrointestinal transit in the rat

We studied the interactive effect of dexmedetomidine and morphine on gastric emptying and gastrointestinal transit in the rat. In one group of rats, to examine the interactive effect on gastrointestinal transit, the two drugs were injected i.p. in a fixed ratio (30: 1)--that of their ED50 values--in six doses (0.062-1.075 mg kg-1), each to a different group of 5-8 male rats for each dose. In another group, to examine the interactive effect on gastric emptying, either dexmedetomidine or saline was injected with saline or with the ED25 or ED50 of morphine (0.22 and 2.8 mg kg-1, respectively). In both groups, at 30 min, radiolabelled saline 1 ml was infused into the stomach; at 1 h, gastric emptying or gastrointestinal transit was calculated by measuring the radioactivity in the gastrointestinal tract. Morphine and dexmedetomidine produced a supra-additive inhibitory effect on gastrointestinal transit (P = 0.02). Dexmedetomidine 0.01 mg kg-1, which itself significantly inhibited gastric emptying (P < 0.01), did not significantly alter the inhibitory effect of morphine on gastric emptying. Therefore, in rats, dexmedetomidine markedly enhanced the inhibitory effect of morphine on gastrointestinal transit, but it did not significantly alter the effect on gastric emptying.      

A comparison of the effects of propofol and midazolam on memory during two levels of sedation by using target-controlled infusion

We examined memory during sedation with target-controlled infusions of propofol and midazolam in a double-blinded five-way, cross-over study in 10 volunteers. Each active drug infusion was targeted to sedation level 1 (asleep) and level 4 (lethargic) as determined with the Observer Assessment of Alertness/Sedation scale. At the target level of sedation, drug concentration was clamped for 30 min, during which time neutral words were presented. After 2 h, explicit memory was assessed by recall, and implicit memory by using a wordstem completion test. Venous drug concentrations (mean +/- SD) were 1350 ng/mL (+/-332 ng/mL) for propofol and 208 ng/mL (+/-112 ng/mL) for midazolam during Observer Assessment of Alertness/Sedation scale level 4; and 1620 ng/mL (+/-357 ng/mL) and 249 ng/mL (+/-82 ng/mL) respectively during level 1. The wordstem completion test frequencies at low level sedation were significantly higher than spontaneous frequencies (8.7% + 2.4%; P: < 0.05 in all cases), and lower than during placebo (33.6% + 23%) (P: < 0.05 in all cases, except P: = 0.076 for propofol at level 4). Clinically distinct levels of sedation were accompanied by small differences in venous propofol or midazolam concentrations. This indicates steep concentration-effect relationships. Neutral information is still memorized during low-level sedation with both drugs. The memory effect of propofol and midazolam did not differ significantly. Implications: Implicit memory can occur during different states of consciousness and might lead to psychological damage. In 10 volunteers, implicit memory was investigated during sedation with propofol and midazolam in a double-blinded, placebo-controlled study. To compare the effects of both drugs, they were titrated using a computer-controlled infusion system to produce similar high and low levels of sedation.     

Cardiovascular Responses during Sedation after Coronary Revascularization: Incidence of Myocardial Ischemia and Hemodynamic Episodes with Propofol Versus Midazolam

Background: Propofol sedation offers advantages for titration and rapid emergence in the critically ill patient, but concern for adverse hemodynamic effects potentially limits its use in these patients. The current study compares the cardiovascular effects of sedation with propofol versus midazolam during the first 12 h after coronary revascularization.

Methods: Three hundred fifty-one patients undergoing coronary revascularization were anesthetized using a standardized sufentanil/midazolam regimen, and assigned randomly to 12 h of sedation with either propofol or midazolam while tracheally intubated. The incidence and characteristics of hemodynamic episodes, defined as heart rate less than 60 or greater than 100 beats/min or systolic blood pressure greater than 140 or less than 90 mmHg, were determined using data electronically recorded at 1-min intervals. The presence of myocardial ischemia was determined using continuous three-channel Holter electrocardiography (ECG) and of myocardial infarctions (MI) using 12-lead ECG (Q wave MI, Minnesota Code) or creatine kinase isoenzymes (CK-MB) analysis (non-Q wave MI, peak CK-MB > 70 ng/ml, or CK-MB > 70 IU/l).

Results: Ninety-three percent of patients in both treatment groups had at least one hemodynamic episode during the period of postoperative sedation. Propofol sedation resulted in a 17% lower incidence of tachycardia (58% vs. 70%, propofol vs. midazolam; P = 0.04), a 28% lower incidence of hypertension (39% vs. 54%; P = 0.02), and a greater incidence of hypotension (68% vs. 51%; P = 0.01). Despite these hemodynamic effects, the incidence of myocardial ischemia did not differ between treatment groups (12% propofol vs. 13% midazolam; P = 0.66), nor did its severity, as measured by ischemic minutes per hour monitored (8.7+/-5.8 vs. 6.2+/-4.6 min/h, propofol vs. midazolam; P = 0.19) or ischemic area under the curve (6.8+/-4.0 vs. 5.3+/-4.2; P = 0.37). The incidence of cardiac death (one per group), Q wave MI (propofol, n = 7; midazolam, n = 3; P = 0.27), or non Q wave MI (propofol, n = 16; midazolam, n = 18; P = 0.81) did not differ between treatment groups.     

Performance of AEP Monitor/2-derived composite index as an indicator for depth of sedation with midazolam and alfentanil during gastrointestinal endoscopy

BACKGROUND AND OBJECTIVE: The A-Line auditory evoked potential index (AAI) (AEP Monitor/2, Danmeter A/S, Odense, Denmark) is a newly developed composite parameter representing the degree of hypnosis. We conducted a prospective, observational study to explore the performance and validity of the AAI during conventional sedation for gastrointestinal (GI) endoscopy. METHODS: Thirty adults of either sex, age <65, scheduled for combined oesophagogastroduodenoscopy (OGD) and colonoscopy under sedation with intravenous (i.v.) midazolam and alfentanil were enrolled. The sedative end-point was set at the Observer's Assessment of Alertness/Sedation (OAA/S) score less than 4. An AEP Monitor/2 was used in all patients. AAI, sedation scores, heart rate (HR), blood pressure (BP) and SPO2 were recorded every 2 min up to the end of the procedure. Receiver operator characteristic analysis was used to test validity and to select optimal sedation. RESULTS: There was a significantly positive correlation between AAI and OAA/S scores (rho = 0.886; P < 0.001). The AAI also showed significant differences between subsequent levels of sedation scores (P < 0.001). AAI greater than 54 indicated fully awake or minimal sedation and values between 54 and 42 were suggestive of moderate sedation. Values between 42 and 34 were associated with moderate to deep sedation and readings below 34 were associated with deep sedation. The relative risk of SPO2 < 95% for OAA/S = 2 compared with 3 was 15.98 (95% confidence interval (CI): 3.94-64.81). CONCLUSIONS: AAI is an effective tool for monitoring sedation during GI endoscopy induced by i.v. midazolam and alfentanil.     

Oral ketamine/midazolam is superior to intramuscular meperidine, promethazine, and chlorpromazine for pediatric cardiac catheterization

An IM combination of meperidine, promethazine, and chlorpromazine (DPT) has been given as sedation for pediatric procedures for more than 40 years. We compared this IM combination to oral (PO) ketamine/midazolam in children having cardiac catheterization. A total of 51 children, ages 9 mo to 10 yr, were enrolled and randomized in this double-blinded study. All children received an IM injection at time zero and PO fluid 15 minutes later. We observed acceptance of medication, onset of sedation and sleep, and sedative efficacy. The cardiorespiratory changes were evaluated. Sedation was supplemented with IV propofol as required. Recovery time, parental satisfaction, and patient amnesia were assessed. Ketamine/midazolam given PO was better tolerated (P < 0.0005), had more rapid onset (P < 0.001), and provided superior sedation (P < 0.005). Respiratory rate decreased after IM DPT only. Heart rate and shortening fraction were stable. Oxygen saturation and mean blood pressure decreased minimally in both groups. Supplemental propofol was more frequently required (P < or = 0.02) and in larger doses (P < 0.05) after IM DPT. Parental satisfaction ratings were higher (P < 0.005) and amnesia was more reliably obtained (P = 0.007) with PO ketamine/midazolam. Two patients needed airway support after the PO medication, as did two other patients when PO ketamine/midazolam was supplemented with IV propofol. Although PO ketamine/midazolam provided superior sedation and amnesia compared to IM DPT, this regimen may require the supervision of an anesthesiologist for safe use. IMPLICATIONS: Oral medication can be superior to IM injections for sedating children with congenital heart disease; however, the safety of all medications remains an issue.     

Propofol sedation and gastric emptying in volunteers

Background : The purpose of this study was to evaluate the effects of light propofol sedation on gastric emptying and orocecal transit time (OCT).
Methods : Ten healthy male volunteers were studied on 2 occasions separated by at least 1 week and were randomly allocated to receive either propofol sedation or i.v. saline as a control. During propofol sedation the volunteers were sedated to grade 2–3 on a 5-grade scale. This was achieved by a propofol infusion of 5 mg kg^-1 h^-1 initially, which was then titrated down to a dose of 2.4±0.7 mg kg^-1 h^-1 Paracetamol absorption was used as an indirect measure of the rate of gastric emptying and OCT was determined by use of the hydrogen breath test after ingestion of raffinose. Student's t -test for paired samples was used and the results are presented as means± SD.
Results: During propofol sedation the maximum concentration of paracetamol (C_max) was 115±26.8μl/L, time to peak concentration (T_max) 50±38.8 min, and the area under the curve during the first 60 min (AUC₆₀4793±1538 μmolXmin/L, versus C_max 99±20.8, T_max 69±41.9 and AUC₆₀ 3897±1310 during saline infusion. These differences were not statistically significant. OCT was significantly shorter during the control study, 180±32.4 min, than during propofol sedation, 217±64.9 min (P<0.05).
Conclusion : This study in volunteers has shown that gastric emptying of liquids seems uninfluenced by light propofol sedation. OCT was slightly prolonged during light propofol sedation.     

Timing of midazolam and propofol administration for co-induction of anaesthesia

We aimed to determine the optimum timing of midazolam administration prior to propofol to achieve the maximal reduction in the dose of propofol required to induce anaesthesia. Female (ASA 1-2) patients, aged 18 to 45 years, weighing 40 to 75 kg and scheduled for gynaecological surgery were eligible for the study. Consenting patients were randomly assigned to six groups. Group 1 received saline and Groups 2 to 6 received midazolam 3 mg at 1, 2, 4, 6 or 10 minutes respectively prior to propofol (n = 20 to 22 per group) in a blinded manner. Propofol was administered i.v. over 10 seconds and flushed in with saline 5 ml. Two minutes later, the patient's response to pressure applied to the finger was determined as an index of loss of consciousness. The ED50 of propofol in each group was determined by the up-and-down method. Propofol ED50 was reduced to 34 to 67% (P < 0.001) in the midazolam treated groups. There was no significant (P = 0.14) difference in propofol ED50 among the five groups which received midazolam. Patients who received midazolam had less recollection of events surrounding induction (P < 0.001) and recalled the induction experience as being more pleasant (P = 0.03) than those who did not receive midazolam. These results indicate that midazolam may be given up to 10 minutes prior to propofol and still achieve a substantial dose reduction.     

Effects of nalbuphine, pentazocine and U50488H on gastric emptying and gastrointestinal transit in the rat

We studied the effect of mixed agonist-antagonist opioids (nalbuphine and pentazocine) and a kappa opioid agonist (U50488H) on gastric emptying and gastrointestinal transit, and their interactions with morphine in rats. In each group, nalbuphine (0.01-30 mg kg-1), pentazocine (1-30 mg kg-1), U50488H (1-100 mg kg(-1)1) or saline was injected i.p. at 0 min. Another four groups of rats received morphine 13.4 mg kg-1 (ED75) and one of the following substances: saline, nalbuphine, pentazocine or U50488H. In both groups, at 30 min, radiolabelled saline 1 ml was infused into the stomach; at 1 h, gastric emptying and gastrointestinal transit were calculated by measuring the radioactivity in the gastrointestinal tract. Slopes for dose-response curves were determined. Nalbuphine significantly, but only weakly, delayed gastric emptying (P < 0.0005) and gastrointestinal transit (P < 0.01). Pentazocine markedly inhibited both, whereas U50488H did not significantly inhibit either. The slopes of the dose-response curves for nalbuphine, but not for pentazocine, on both gastric emptying and gastrointestinal transit were significantly less steep than those for morphine. Nalbuphine significantly antagonized the inhibitory effect of morphine on gastric emptying (P = 0.005) and gastrointestinal transit (P = 0.02), whereas pentazocine and U50488H did not. Nalbuphine and pentazocine delay gastric emptying and gastrointestinal transit, possibly by different mechanisms.      

Propofol and midazolam versus propofol alone for sedation following coronary artery bypass grafting: a randomized,placebo-controlled trial

The aim was to compare the efficacy and side-effects of propofol combined with a constant, low dose of midazolam versus propofol alone for sedation. In a prospective, randomized and double-blinded study, 60 male patients scheduled for elective coronary bypass grafting were enrolled. Postoperatively, patients were stratified to receive either a continuous intravenous infusion of midazolam 1 mg/h or placebo. Target Ramsay sedation score was 3 to 5 corresponding to conscious sedation. An intention-to-treat design for propofol was performed to reach target sedation. Efficacy of sedation was statistically significantly higher in the group midazolam + intention-to-treat with propofol compared with the group placebo + intention-to-treat with propofol (91% vs 79%; P=0.0005). Nine of 27 patients in the midazolam group (33.4%) and nine of 26 patients in the placebo group (34.6%) needed no supplementary propofol. Weaning time from mechanical ventilation was longer in the midazolam group whether or not they required supplemental propofol when compared with placebo group (all: 432 +/- 218 min vs 319 +/- 223 min; P=0.04; supplementary propofol: 424 +/- 234 min vs 265 +/- 175 min; P=0.03). The cumulative number of patients remaining intubated was significantly higher in the group midazolam + propofol compared with the group placebo + propofol (P=0.03). In conclusion, target sedation is reached slightly more often by the co-administration of propofol and a low dose of midazolam, but weaning time from mechanical ventilation is prolonged by the co-administration of propofol and a low dose of midazolam.     

Does propofol anesthesia affect intraoperative parathyroid hormone levels? A randomized, prospective trial

BACKGROUND: Intravenous propofol (2,6-diisopropylphenol) infusion is used commonly for sedation/anesthesia during operations. Several authors have reported that propofol can interfere with intact parathyroid hormone (PTH) testing in vitro. Therefore, many surgeons avoid propofol during parathyroidectomy. METHODS: To determine whether propofol affects intraoperative PTH levels in vivo, we randomly assigned 34 patients (80% power; alpha < .05) with secondary hyperparathyroidism to undergo surgery for dialysis access. Patients were assigned randomly to local anesthesia with either propofol (n = 17 patients) or midazolam (n = 17 patients) sedation. PTH values were obtained before the procedure and at 10 minutes and 30 minutes after the start of the propofol or midazolam. RESULTS: Median preoperative serum PTH and calcium levels were 175 pg/mL (range, 27-2646 pg/mL) and 9.2 mg/dL (range, 8.1-10.8 mg/dL), respectively. There was no statistically significant difference between the PTH levels in the 2 groups at each of our time points. There was also no difference in the percentage of change from baseline in the PTH values between our 2 groups. No patient in either group had a sustained drop in their PTH level of greater than 50%. CONCLUSIONS: Intravenous propofol infusion does not alter PTH levels significantly during the operation. Therefore, we believe the intraoperative PTH assay can be used safely during propofol sedation when parathyroid surgical procedures are being performed.     

The alpha2-adrenergic receptor antagonist yohimbine improves endotoxin-induced inhibition of gastrointestinal motility in mice

Background: Sepsis inhibits gastrointestinal motility. Although the exactmechanism of this is unclear, lipopolysaccharide is known toactivate macrophages in the gastrointestinal wall, which upregulatetheir expression of inducible nitric oxide synthase (iNOS).This leads to an increased production of nitric oxide, whichrelaxes the gastrointestinal muscles. We studied endotoxaemicmice to determine whether yohimbine improved delayed gastricemptying and gastrointestinal transit. Methods: Male Balb/c mice (n = 49) were randomly allocated to two groups,and either yohimbine 25 µg or saline was injected s.c.Four hours later, mice in each group were further randomly allocatedto two groups, and either lipopolysaccharide 100 µg orsaline was injected intraperitoneally. Eight hours later, liquidcontaining fluorescent microbeads was infused into the stomach,and 30 min later, gastric emptying and gastrointestinal transitwere measured using flow cytometry. We also studied whetheryohimbine given after injection of lipopolysaccharide was effective(n = 22). In another group of mice (n = 32), iNOS in the gastrointestinaltract was measured using western blotting. Results: Lipopolysaccharide significantly inhibited gastric emptyingand gastrointestinal transit. Yohimbine, given before or afterlipopolysaccharide, significantly attenuated the inhibitoryeffects of lipopolysaccharide. Lipopolysaccharide increasedthe expression of iNOS in the small intestine and yohimbinesuppressed the effects of lipopolysaccharide. Conclusions: In endotoxaemic mice, yohimbine improved delayed gastric emptyingand gastrointestinal transit, possibly by downregulating lipopolysaccharide-inducedincreased expression of iNOS.     

Monitoring sedation in critically ill patients: bispectral index, Ramsay and observer scales

BACKGROUND AND OBJECTIVE: Sedation is commonly required by critically ill patients and inadequate sedation may be hazardous. Traditionally, subjective scales have been used for monitoring sedation. Bispectral index has been proposed, although its utility in the intensive care unit is debated. Our aim was to evaluate the depth of sedation in intubated surgical critically ill patients by means of two sedation scales (Ramsay and Observer's Assessment of Alertness and Sedation) and bispectral index. Methods: Sedation was assessed prospectively in 50 postoperative intubated patients requiring at least 24 h of sedation (35 propofol, 15 midazolam/fentanyl), every 8 h for a 24 -h period. The bispectral index value recorded was the mean value obtained during a 10-min observation period, whenever the quality signal index was above 75% and the electromyographic signal was below 25%. RESULTS: Most of the patients (78%) were oversedated (bispectral index < 60). The three sedation scores (global data) correlated significantly (P < 0.001). This correlation was lost in the midazolam group in which the patients were also significantly more sedated than the propofol group (P = 0.001). The correlation between the bispectral index and the scales in the midazolam group reappeared when the measurements with a Ramsay = 6 or an Observer's Assessment of Alertness and Sedation = 1 were excluded. CONCLUSIONS: Sedation should be monitored routinely in intensive care units. The Ramsay and the Observer's Assessment of Alertness and Sedation scales showed equal efficacy. Bispectral index might prove useful for discriminating between deeper levels of sedation.     

Methylprednisolone reduces pain, emesis, and fatigue after breast augmentation surgery: a single-dose, randomized, parallel-group study with methylprednisolone 125 mg, parecoxib 40 mg, and placebo

We compared methylprednisolone 125 mg IV (n = 68) and parecoxib 40 mg IV (n = 68) with placebo (n = 68) given before breast augmentation surgery in a randomized, double-blind parallel group study. Surgery was performed under local anesthesia combined with propofol/fentanyl sedation. Methylprednisolone and parecoxib decreased pain at rest and dynamic pain intensity from 1 to 6 h after surgery compared with placebo (mean summed pain intensity(1-6 h): methylprednisolone [17.25; 95% confidence interval [CI], 14.85-19.65] versus placebo [21.7; 95% CI, 19.3-24.1]; P < 0.03; parecoxib [15.25; 95% CI, 13.25-17.25] versus placebo; P < 0.001; mean summed dynamic pain intensity(1-6 h): methylprednisolone [22.7; 95% CI, 20.1-23.3] versus placebo [28.4; 95% CI, 26.0-30.8]; P < 0.01; parecoxib [20.9; 95% CI, 18.6-23.2] versus placebo; P < 0.001). Both rescue drug consumption and actual pain (all observations before and after rescue) during the first 6 h were similar in the two active drug groups and significantly reduced compared with placebo. Using a composite score of actual pain intensity and rescue analgesic use, the active drugs were significantly superior to placebo (P < 0.001 for both active drugs). Postoperative nausea and vomiting was reduced after methylprednisolone administration (incidence, 30%), but not after parecoxib (incidence, 37%), during the first 24 h compared with placebo (incidence, 60%; P < 0.001). Fatigue was reduced by methylprednisolone (incidence, 44%), but not by parecoxib (incidence, 59%), compared with placebo (incidence, 66%; P < 0.05). In conclusion, methylprednisolone 125 mg IV given before breast augmentation surgery had analgesic and rescue analgesic-sparing effects comparable with those of parecoxib 40 mg IV. Methylprednisolone, but not parecoxib, reduced nausea, vomiting, and fatigue.     

Differences between Midazolam and Propofol Sedation on Upper Airway Collapsibility Using Dynamic Negative Airway Pressure

Background: Upper airway obstruction (UAO) during sedation can often cause clinically significant adverse events. Direct comparison of different drugs' propensities for UAO may improve selection of appropriate sedating agents. The authors used the application of negative airway pressure to determine the pressure that causes UAO in healthy subjects sedated with midazolam or propofol infusions.

Methods: Twenty subjects (12 male and 8 female) completed the study. After achieving equivalent levels of sedation, the subjects' ventilation, end-tidal gases, respiratory inductance plethysmographic signals, and Bispectral Index values were monitored for 5 min. Negative airway pressure was then applied via a facemask in steps of 3 cm H2O from -3 to -18 cm H2O. UAO was assessed by cessation of inspiratory airflow and asynchrony between abdomen and chest respiratory inductance plethysmographic signals.

Results: Equivalent levels of sedation were achieved with both drugs with average (+/- SD) Bispectral Index levels of 75 +/- 5. Resting ventilation was mildly reduced without any changes in end-tidal pressure of carbon dioxide. There was no difference between the drugs in the negative pressure resulting in UAO. Five female subjects and one male subject with midazolam and four female subjects and one male subject with propofol did not show any UAO even at -18 cm H2O. Compared with males, female subjects required more negative pressures to cause UAO with midazolam (P = 0.02) but not with propofol (P = 0.1).