A double-blind, randomized comparison of i.v. lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model

BACKGROUND: Benzodiazepines, such as lorazepam and midazolam, are frequently administered to surgical intensive care unit (ICU) patients for postoperative sedation. To date, the pharmacology of lorazepam in critically ill patients has not been described. The aim of the current study was to characterize and compare the pharmacokinetics and pharmacodynamics of lorazepam and midazolam administered as continuous intravenous infusions for postoperative sedation of surgical ICU patients. METHODS: With Institutional Review Board approval, 24 consenting adult surgical patients were given either lorazepam or midazolam in a double-blind fashion (together with either intravenous fentanyl or epidural morphine for analgesia) through target-controlled intravenous infusions titrated to maintain a moderate level of sedation for 12-72 h postoperatively. Moderate sedation was defined as a Ramsay Sedation Scale score of 3 or 4. Sedation scores were measured, together with benzodiazepine plasma concentrations. Population pharmacokinetic and pharmacodynamic parameters were estimated using nonlinear mixed-effects modeling. RESULTS: A two-compartment model best described the pharmacokinetics of both lorazepam and midazolam. The pharmacodynamic model predicted depth of sedation for both midazolam and lorazepam with 76% accuracy. The estimated sedative potency of lorazepam was twice that of midazolam. The predicted C50,ss (plasma benzodiazepine concentrations where P(Sedation > or = ss) = 50%) values for midazolam (sedation score [SS] > or = n, where n = a Ramsay Sedation Score of 2, 3, ... 6) were 68, 101, 208, 304, and 375 ng/ml. The corresponding predicted C50,ss values for lorazepam were 34, 51, 104, 152, and 188 ng/ml, respectively. Age, fentanyl administration, and the resolving effects of surgery and anesthesia were significant covariates of benzodiazepine sedation. The relative amnestic potency of lorazepam to midazolam was 4 (observed). The predicted emergence times from sedation after a 72-h benzodiazepine infusion for light (SS = 3) and deep (SS = 5) sedation in a typical patient were 3.6 and 14.9 h for midazolam infusions and 11.9 and 31.1 h for lorazepam infusions, respectively. CONCLUSIONS: The pharmacology of intravenous infusions of lorazepam differs significantly from that of midazolam in critically ill patients. This results in significant delays in emergence from sedation with lorazepam as compared with midazolam when administered for ICU sedation.     

Nerve stimulator-guided paravertebral blockade combined with sevoflurane sedation versus general anesthesia with systemic analgesia for postherniorrhaphy pain relief in children: a prospective randomized trial

BACKGROUND: Improvement of the duration of postoperative analgesia is desirable in children undergoing inguinal hernia repair. METHODS: Fifty children aged 5-12 yr were prospectively randomized to receive either paravertebral nerve blockade or general anesthesia (sevoflurane-fentanyl-nitrous oxide-oxygen) combined with standardized postoperative systemic analgesia, both combined with light sevoflurane anesthesia, for inguinal hernia repair. RESULTS: Mean pain scores were significantly lower in paravertebral nerve blockade patients compared with patients treated with systemic analgesia during the entire 48-h observational period (P < 0.05). Analgesic consumption was significantly higher in the systemic analgesia group (88%) compared with the paravertebral nerve blockade group (32%) (P < 0.001). Parental satisfaction was significantly higher (80 vs. 48%; P < 0.05) and same-day discharge was possible in a higher proportion of patients in the paravertebral blockade group (80% vs. 52%; P < 0.05). CONCLUSIONS: Paravertebral nerve blockade was associated with improved postoperative pain relief; reduced analgesic consumption, and faster hospital discharge compared with a systemic analgesia protocol in children undergoing herniorrhaphy.     

Facilitating coping behavior in children prior to dental general anesthesia: a randomized controlled trial

BACKGROUND: The aim of this study was to establish the efficacy of two different preparation packages, a paper-based cartoon and an interactive computer, at facilitating coping behavior in children undergoing dental general anesthetic (DGA) tooth extraction. METHOD: A total of 198 children were allocated randomly to computer, cartoon or control groups. A Visual Analog Scale (VAS) and Modified Child Dental Anxiety Scale (MCDAS) were used to compare preoperative anxiety levels between the three study groups. Blinded observers then scored behavior at both anesthesia induction and upon recovery using a VAS for each (0 = coped/no distress and 10 = no coping/high distress). RESULTS: The children's median age was 5 (range 3-10) years, 57% were boys, a median of seven teeth were extracted (range 1-20). Preoperative anxiety was similar for all preparation groups; with 24% of all children categorized 'phobic' using MCDAS. The median induction (coping) VAS level for both the computer and the cartoon groups was '1' (range 0-10), compared with the control group level of '3' (range 0-10). The median recovery (coping) VAS levels were: computer group: 0 (range 0-10), cartoon group: 4 (range 0-10) and control group: 2.5 (range 0-10). The Mann-Whitney U-test showed that the computer group coped significantly better than the control group at induction (P = 0.014) and significantly better than the cartoon group upon recovery (P = 0.016). The statistical power for detecting differences between groups (computer/cartoon versus control) was calculated to be 90%, based on pilot study data. CONCLUSIONS: The computer preparation package facilitated coping behavior in children undergoing DGA induction.     

Preoperative peribulbar block in patients undergoing retinal detachment surgery under general anesthesia: a randomized double-blind study

Retinal detachment surgery is frequently associated with significant postoperative pain and emesis in adults. In this randomized, double-blind, controlled study we sought to demonstrate that 1% ropivacaine peribulbar (PB) block in conjunction with general anesthesia (GA) improves operative conditions and postoperative analgesia compared with GA combined with subcutaneous normal saline injection into the inferior eyelid. Thirty-one patients were included in each group. Anesthesia was performed with target-controlled infusion propofol and continuous remifentanil infusion adjusted to maintain bispectral index values between 40 and 50. Postoperative analgesia included fixed-dose IV infusion of propacetamol and IV injection of nefopam via a patient-controlled analgesia device. Tramadol was infused IV as rescue medication. Demographic data were comparable between the groups and bispectral index values were maintained at the objective target. In the PB group, fewer patients presented an oculocardiac reflex (6 versus 17; P < 0.01); bleeding interfering with the surgical field was reduced (1 versus 11 patients; P < 0.01); mean time to first nefopam request was longer (148 +/- 99 versus 46 +/- 58 min; P < 0.01); mean nefopam consumption was diminished during the first 6 h after tracheal extubation (18.9 +/- 13.9 versus 28.5 +/- 14.7 mg; P < 0.05); immediate postoperative pain scores were lower; and fewer patients required rescue medication (5 versus 23; P < 0.01). The two groups were similar with respect to the incidence of postoperative nausea and vomiting. Overall, PB block combined with GA improved operating conditions and postoperative analgesia in retinal detachment surgery.     

Postoperative analgesia after arthroscopic knee surgery: a randomized, prospective, double-blind study of intravenous regional analgesia versus intra-articular analgesia.

SUMMARY: The aim of this study was to determine the quality of postoperative analgesia in patients undergoing arthroscopic knee surgery using preoperative intravenous regional analgesia. After initial consultation with a statistician, we allocated 36 patients randomly and double-blind to 1 of 3 groups. Group A received intravenous regional analgesia preoperatively, group B received standard postperative intra-articular analgesia, and group C received saline and acted as the placebo. Our results showed no statistically significant difference in pain levels between the groups. However, there was a significantly larger amount of morphine administered by patient-controlled pumps in the placebo group when compared with the 2 treatment groups. There was no such difference between the 2 treatment groups. We concluded that preoperative regional analgesia in this setting is as good as but no better than intra-articular analgesia and that neither technique has any advantages over diclofenac plus patient-controlled analgesia.     

General versus spinal anesthesia with different forms of sedation in patients undergoing radical retropubic prostatectomy: Results of a prospective, randomized study

AIM: To assess the impact of spinal anesthesia (SpA) combined with three different forms of conscious sedation on intraoperative and postoperative outcome in patients undergoing radical retropubic prostatectomy (RRP) for organ confined prostate cancer (pCa). METHODS: A total of 121 consecutive patients with pCa undergoing RRP were randomized into four groups. They were randomized as follows: group 1 (general anesthesia: 34 patients), group 2 (lumbar 2 to lumbar 3 interspace SpA with diazepam as sedative agent: 28), group 3 (SpA with propofol: 30), and group 4 (SpA with midazolam: 29). Intraoperative and perioperative parameters were collected. RESULTS: The present study showed that muscle relaxation throughout RRP was not different in the four groups; bleeding was significantly (P = 0.04) lower with SpA, regardless of the form of sedation. Group 3 patients reported the best postoperative oxygen saturation percentage by pulse oximetry and sedation score (P = 0.02; d.f. = 3 and P < 0.0001; d.f. = 3, respectively), the shortest waiting time in the postoperative holding area (P < 0.001; d.f. = 3), the lowest pain on postoperative day 1 (P = 0.0004; d.f. = 3), and the highest frequency of first flatus passage (P = 0.0001; d.f. = 3). A higher number of group 4 patients were able to carry out unassisted ambulation (P < 0.0001; d.f. = 3). CONCLUSIONS: Conscious sedation coupled with SpA is a safe, reliable and effective procedure for patients undergoing RRP. The use of propofol as sedative agent offers several advantages both over other types of conscious sedation and general anesthesia.     

Dexmedetomidine,morphine, propofol vs midazolam,morphine, propofol for conscious sedation in rhinoplasty under local anesthesia. A prospective,randomized study

BackgroundMonitored anesthesia care (MAC) has been proposed as one of the suitable techniques for rhinoplasty. In this study our aim was to compare the effects of dexmedetomidine with morphine and propofol vs benzodiazepines with morphine and propofol as adjuncts to local anesthesia – on analgesia, sedation, respiratory and hemodynamics variables and surgeon and patient satisfaction.MethodsIn this prospective, double-blind, comparative study, 60 patients undergoing rhinoplasty by local anesthesia randomly received intravenous sedation of either: dexmedetomidine (Dex group) or midazolam (Mid group) in combination with morphine and propofol. Level of sedation was assessed by using the Observer’s Assessment Alertness/Sedation Scale (OAA/S). Pain on local anesthesia injection was assessed by a visual analog scale. Surgeon’s satisfaction also can be assessed by using a 3-grades score, the surgeon assessed the quality of surgical bleeding. Mean Arterial Pressure (MAP) and heart rate (HR) were assessed and recorded. Patients’ satisfaction, visual analog scale for intraoperative pain, and total amount of propofol used intraoperatively. Adverse effects were also recorded.ResultsIn Mid group patients were earlier to reach adequate sedation level than in Dex group, but they felt more pain either on local anesthetic injection or during operation. Intraoperative mean arterial blood pressure and heart rate in Dex group were lower than their baseline values and the corresponding values in Mid group. The total amount of propofol needed for Mid group was much higher than in Dex group. Patient satisfaction was higher in Dex group. Time of surgery was longer in Mid group. Both groups were similar in sedation recovery and ward discharge times, as well as, incidence of side effects.ConclusionDexmedetomidine sedation with morphine and propofol in rhinoplasty performed under local anesthesia was associated with shorter surgery time, greater patient and surgeon satisfaction, and lower pain scores with no adverse effects, when compared to midazolam sedation with morphine and propofol.     

Comparison of the effects of intranasal midazolam versus different doses of intranasal ketamine on reducing preoperative pediatric anxiety: a prospective randomized clinical trial

Purpose

To compare the effects of intranasal midazolam versus different doses of intranasal ketamine on reducing preoperative pediatric anxiety.

Methods

The participants of this double-blinded clinical trial study consisted of 120 children aged between 2 and 8 years. They were chosen for elective surgery and randomly assigned to four equal groups. For reducing preoperative anxiety, in the first group midazolam 0.2 mg/kg, in the second group (K1) ketamine 0.5 mg/kg, in the third group (K2) ketamine 3 mg/kg, and in the fourth group normal saline 1 drop/5 kg were administered intranasally. After 15 min, severity of anxiety was assessed with the modified Yale preoperative anxiety score (m-Yale PAS), and level of sedation was evaluated by the Ramsay Sedation Scale before intravenous catheterization. All data were transferred to SPSS-10 software and analyzed statistically with ANOVA, Kruskal–Wallis, and Mann–Whitney tests. A p value < 0.05 was considered meaningful.

Results

The mean of m-Yale PAS in midazolam group was significantly lower than the other three groups (p < 0.05). Regarding this score, there was no significant statistical difference between K2 and normal saline groups (p = 0.944), but the differences between K1 and K2 (p = 0.034) and also between K1 and normal saline (p = 0.049) groups were significant statistically. The Ramsay Sedation Scale in the midazolam group was significantly higher than the other three groups (p < 0.05). By this scale, there was no significant statistical difference between (K2) and normal saline groups (p = 0.940). The differences between (K1) and normal saline (p = 0.045) and also between (K1) and (K2) groups (p = 0.009) were significant statistically.

Conclusion

Intranasal midazolam was more effective than low- or high-dose intranasal ketamine in reducing preoperative pediatric anxiety. The lower dose of ketamine reduced preoperative anxiety more than a higher dose of ketamine, which may be clinically insignificant.     

0.5% versus 1.0% 2-chloroprocaine for intravenous regional anesthesia: a prospective, randomized, double-blind trial

In this randomized prospective double-blind study we tested the hypothesis that compared with 40 mL chloroprocaine 0.5%, 40 mL chloroprocaine 1% results in an earlier onset to analgesia duration and improves distal tourniquet tolerance in 150 patients undergoing forearm surgery under IV regional anesthesia using a double-cuff technique, switching from the proximal to the distal cuff was performed if pain scores increased above 4 of 10. Switching to the distal cuff resulted in pain scores below 4 in 69% of patients in the 0.5% group and in 88% of patients in the 1% group (P = 0.047). In addition, both groups differed in the sustained effect on distal tourniquet pain (P = 0.020). Time between injection and onset to analgesia duration was 13 +/- 1 min in the 0.5% group and 11 +/- 1 min in the 1% group (P = 0.0006). On release of the tourniquet, signs of systemic local anesthetic toxicity occurred in 6 patients of the 0.5% group and 28 of the 1% group (P < 0.0001). We conclude that chloroprocaine 1% resulted in an earlier onset of analgesia and improved distal tourniquet tolerance. However, these beneficial effects must be weighed against a fourfold increase in side effects. IMPLICATIONS: Compared to a standard dose of 40 mL 0.5% chloroprocaine, 40 mL 1% chloroprocaine resulted in an earlier onset of analgesia duration and improved distal tourniquet tolerance during IV regional anesthesia. These beneficial effects must be weighed against a fourfold increase in signs of systemic local anesthetic toxicity.     

Comparison between intranasal dexmedetomidine and intranasal ketamine as premedication for procedural sedation in children undergoing MRI: a double-blind,randomized, placebo-controlled trial

Introduction

Providing anesthesia to children undergoing MRI is challenging. Adequate premedication, administered noninvasively, would make the process smoother. In this study, we compare the efficacy of intranasal dexmedetomidine (DXM) with the intranasal administration of ketamine for procedural sedation in children undergoing MRI.

Methods

We studied 150 children, between 1 and 10 years of age, divided randomly into three groups (DXM, K, and S). For blinding, every child received the intranasal drugs twice; syringe S1, 60 min before, and syringe S2, 30 min before intravenous (IV) cannulation. For children in group DXM, S1 contained DXM (1 μg/kg) and S2 was plain saline. Children in group K received saline in S1 and ketamine (5 mg/kg) in S2 whereas children in group S received saline in both S1 and S2. The child’s response to drug administration, ease of IV cannulation, the satisfaction of the anesthesiologist and child’s parents with the premedication, and the total propofol dose required for the satisfactory conduct of the procedure were compared. We also compared the time to awakening and discharge of the child as well as the occurrence of any side effects with these drugs.

Results

Both DXM and ketamine were equally effective as premedication in these patients. Most of the children accepted the intranasal drugs with minimal discomfort; 90.4 % of the anesthesiologists in the DXM group and 82.7 % in the ketamine group were satisfied with the conditions for IV cannulation whereas only 21.3 % were satisfied in the saline group. The total dose of propofol used was less in the study groups. Furthermore, children in group DXM and group K had earlier awakening and discharge than those in group S.

Conclusion

DXM and ketamine were equally effective, by the intranasal route, as premedication in children undergoing MRI.     

Ropivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, versus bupivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, using patient-controlled epidural analgesia for labor: a double-blind comparison

BACKGROUND: This study compared the administration of 0.1% ropivacaine and 0.5 microg/ml sufentanil with that of 0.1% bupivacaine and 0.5 microg/ml sufentanil via patient-controlled epidural analgesia route during labor. METHODS: Two hundred healthy pregnant women at term with a single fetus with a vertex fetal presentation were randomized in a double-blind fashion to receive either 0.1% ropivacaine and 0.5 microg/ml sufentanil or 0.1% bupivacaine and 0.5 microg/ml sufentanil using a patient-controlled epidural analgesia pump (5-ml bolus dose, 10-min locked-out period, no basal infusion). Pain score on a visual analog scale, Bromage score (0-3), level of sensory block, patient-controlled epidural analgesia ratio, drug use, supplemental boluses, and side effects were recorded at 30 min and then hourly. Mode of delivery, duration of first and second stages of labor, umbilical cord pH, Apgar scores of the newborn, and a measure of maternal satisfaction were recorded after delivery. RESULTS: No differences were seen between the two groups for pain scores on a visual analog scale during labor, volume of anesthetic solution used, mode of delivery, or side effects. Motor block during the first stage of labor was significantly less in the ropivacaine group than in the bupivacaine group (no motor block in 97.8 of patients vs. 88.3%, respectively; P < 0.01). Duration of the second stage of labor was shorter in the ropivacaine group (1.3 +/- 1.0 vs. 1.5 +/- 1.2 h [mean +/- SD]; P < 0.05). Maternal satisfaction was greater in the bupivacaine group (91 +/- 13 mm for contraction, 89 +/- 19 mm for delivery on a visual scale: 0 = not satisfied at all, 100 = fully satisfied) than in the ropivacaine group (84 +/- 21 and 80 +/- 25 mm; P < 0.0001). Patients in the ropivacaine group requested more supplemental boluses to achieve analgesia during the second stage of labor than those in the bupivacaine group (29.7 vs. 19.8%, respectively, requested one or more supplemental boluses; P < 0.05). CONCLUSIONS: Delivered as patient-controlled epidural analgesia, 0.1% ropivacaine and 0.5 microg/ml sufentanil produce less motor block but are clinically less potent than 0.1% bupivacaine and 0.5 microg/ml sufentanil.